PMID- 22772788 TI - Prevalence of histology proven Helicobacter pylori infection in a cohort of Sri Lankan patients with gastric carcinoma. PMID- 22772789 TI - Conidiobolus coranatus infection of the para-nasal sinuses masquerading as a sino nasal tumour. PMID- 22772790 TI - Neck stiffness and papilloedema due to Harada syndrome. PMID- 22772791 TI - Treatment-responsive, reversible, autoimmune encephalitis in a child. PMID- 22772792 TI - Could the latex of Semecarpus anacardium (Kiri Badulla) cause nephrotic syndrome? PMID- 22772793 TI - Intra-uterine fetal blood transfusion. PMID- 22772794 TI - The Sri Lanka Clinical Trials Registry - five years young, and growing. PMID- 22772795 TI - Systhesis, phase transformation and photoluminescence properties of Eu:La(1 x)Gd(x)VO4 nanofibers by electrospinning method. AB - One dimensional Eu:La(1-x)Gd(x)VO(4) nanofibers were successfully prepared via an electrospinning method. Thermogravimetry and differential scanning calorimeter (TG-DSC), X-ray diffraction, Raman spectroscopy, scanning electron microscopy and photoluminescence were used to characterize the samples. The nanofibers crystallized well below 600 degrees C and with the increase of Gd contents, the nanofibers crystallized in a zircon-type structure. The Raman spectra shifted to higher frequency with the increase of Gd content for zircon Eu:La(1-x)Gd(x)VO(4). The peaks of photoluminescence spectra shift towards longer wavelength when Gd replaces La and when x = 0.4, the photoluminescence intensity reaches its maximum value. The band structure and density of states of m-LaVO(4), t-LaVO(4), t LaGdVO(4) and t-GdVO(4) were calculated by local-spin density approximation (LSDA) band theory with Hubbard term of U. The band gap of t-LaGdVO(4) is just the average of t-LaVO(4) and t-GdVO(4). In t-LaGdVO(4), La 5p states are highly localized. PMID- 22772796 TI - Genetics of the renin-angiotensin system with respect to cardiac and blood pressure phenotypes in healthy newborn infants. AB - INTRODUCTION: Left ventricular mass (LVM) is a strong predictor of various heart diseases. We examine the association between the G(-6)A AGT, I/D ACE, A1166C AGTR1, T(-344)C CYP 11beta2, A538G MR and A10631G REN polymorphisms and LVM and blood pressure in newborn infants. MATERIAL AND METHODS: The study included 211 healthy newborn infants. Two-dimensional M-mode echocardiography was used to assess LVM between days 3-4 after birth. Polymorphisms were determined by polymerase chain reaction - restriction fragment length polymorphism (PCR-RLFP). RESULTS: AGTR1 genotype was significantly associated with neonatal systolic blood pressure (>=90 percentile). LVM indexes (LVMIs) were tested for association with genotypes in multivariate analysis. The carriers of the A allele of the AGT polymorphism had significantly higher LVM/body length (BL) values when compared with newborn infants homozygous for the G allele (p adjusted=0.03). The higher LVM/BL values were seen in the carriers of the A alleles of the AGTR1 polymorphism (p adjusted=0.046). All examined indexes (LVM/body surface area (BSA), LVM/BL, LVM/bodyweight (BW)) were associated with CYP11B polymorphism. The newborn infants homozygous for the T allele had significantly higher values of LVM/BSA, LVM/BL, and LVB/BW compared to non-TT-homozygous neonates (p adjusted=0.003; p adjusted=0.003; p adjusted=0.004 respectively). CONCLUSION: The AGT, AGTR1, CYP11beta polymorphisms are associated with increased LVMIs in newborns. This observation indicates that genetic factors may be modulating LVM at birth. PMID- 22772797 TI - Emerging antibody-based products. AB - Antibody-based products are not widely available to address many global health challenges due to high costs, limited manufacturing capacity, and long manufacturing lead times. There are now tremendous opportunities to address these industrialization challenges as a result of revolutionary advances in plant virus based transient expression. This review focuses on some antibody-based products that are in preclinical and clinical development, and have scaled up manufacturing and purification (mg of purified mAb/kg of biomass). Plant virus based antibody products provide lower upfront cost, shorter time to clinical and market supply, and lower cost of goods (COGs). Further, some plant virus-based mAbs may provide improvements in pharmacokinetics, safety and efficacy. PMID- 22772798 TI - Reduction of experimental diabetic vascular leakage and pericyte apoptosis in mice by delivery of alphaA-crystallin with a recombinant adenovirus. AB - AIMS/HYPOTHESIS: The study aimed to evaluate the efficacy of recombinant adenovirus expressing alphaA-crystallin (Ad-alphaAc-Gfp) in reducing pericyte loss within retinal vasculature in early diabetes. METHODS: Diabetes was induced by streptozotocin injection into C57BL/6 mice. Ad-alphaAc-Gfp was delivered by intravitreous injection to the right eyes of mice 2 weeks before induction of diabetes. Vascular leakage was determined by fluorescent angiography, Evans Blue leakage assay and leucocyte adhesion test. Production of alphaA-crystallin was analysed by immunoblotting and double immunostaining and pericyte loss was analysed by pericyte count. RESULTS: Vessel leakage and pericyte loss were observed in the streptozotocin-induced diabetic retina. Decreased abundance of alphaA-crystallin in retinas 2 and 6 months after the induction of diabetes was confirmed by two-dimensional electrophoretic analysis, immunoblotting and RT-PCR. Double immunofluorescence staining for alphaA-crystallin and NG2 chondroitin sulphate proteoglycan revealed that alphaA-crystallin was predominantly produced in the retinal pericyte and that the number of alphaA-crystallin-producing pericytes decreased in the diabetic retina. Retinal infection with Ad-alphaAc-Gfp led to decreased pericyte loss and vascular leakage compared with control. CONCLUSIONS/INTERPRETATION: Intravitreal delivery of Ad-alphaAc-Gfp protects against vascular leakage in the streptozotocin-induced model of diabetes. This effect is associated with the inhibition of diabetic retinal pericyte loss in early diabetes, suggesting that alphaA-crystallin has a role in preventing the pathogenesis of early diabetic retinopathy. PMID- 22772799 TI - Bacterial TIR-containing proteins and host innate immune system evasion. AB - The innate immune system provides the first line of host defence against invading pathogens. Key to upregulation of the innate immune response are Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs) and trigger a signaling pathway culminating in the production of inflammatory mediators. Central to this TLR signaling pathway are heterotypic protein-protein interactions mediated through Toll/interleukin-1 receptor (TIR) domains found in both the cytoplasmic regions of TLRs and adaptor proteins. Pathogenic bacteria have developed a range of ingenuous strategies to evade the host immune mechanisms. Recent work has identified a potentially novel evasion mechanism involving bacterial TIR domain proteins. Such domains have been identified in a wide range of pathogenic bacteria, and there is evidence to suggest that they interfere directly with the TLR signaling pathway and thus inhibit the activation of NF-kappaB. The individual TIR domains from the pathogenic bacteria Salmonella enterica serovar Enteritidis, Brucella sp, uropathogenic E. coli and Yersinia pestis have been analyzed in detail. The individual bacterial TIR domains from these pathogenic bacteria seem to differ in their modes of action and their roles in virulence. Here, we review the current state of knowledge on the possible roles and mechanisms of action of the bacterial TIR domains. PMID- 22772800 TI - Single oral administration of the novel CXCR4 antagonist, KRH-3955, induces an efficient and long-lasting increase of white blood cell count in normal macaques, and prevents CD4 depletion in SHIV-infected macaques: a preliminary study. AB - We evaluated the long-term effects of the single oral administration of a new CXCR4 antagonist, KRH-3955, on elevation of white blood cell (WBC), neutrophil and lymphocyte counts in normal cynomolgus monkeys. In the monkeys treated with 0, 2, 20, 200 mg/kg of the compound, WBC, neutrophil and lymphocyte counts increased dramatically at 2 days after treatment. This effect was dose-dependent, and these cell counts remained elevated 15 days after drug treatment. Since neutrophils are the most abundant WBCs in circulation and bone marrow neutrophil exhaustion impairs the response to bacterial infections, it is intriguing to exploit this pharmacological increase of neutrophils as a tool to address its influence on viral infections in vivo. The SHIV infection studies using the SHIV KS661c/cynomolgus monkey model showed that a single oral administration of KRH 3955 (100 mg/kg) approximately 24 h before virus exposure did not prevent infection, although it did prevent CD4 cell depletion in 3/3 monkeys. Furthermore, single oral administration of the drug 2 weeks before viral exposure rescued CD4 cells in 1/3 monkeys. This prevention of CD4 cell depletion was observed in both blood and lymphoid tissues. These results show that natural course of the SHIV infection is modulated by artificial increase of neutrophils and lymphocytes caused by KRH-3955 in the cynomolgus monkey model. PMID- 22772801 TI - Coupling of enamides with alkynes or arynes for synthesis of substituted pyridines and isoquinolines via amide activation. AB - A novel and general procedure for Cu-catalyzed coupling of enamides with alkynes to synthesize substituted pyridines was developed. The chemistry was allowed to extend to the synthesis of substituted isoquinolines by coupling of enamides with arynes under transition-metal-free conditions. PMID- 22772802 TI - Sponge-like appearance of the liver parenchyma due to fatal intrauterine gas gangrene following mechanical abortion. PMID- 22772803 TI - Postmortem characterization of patients with clinical diagnosis of Plasmodium vivax malaria: to what extent does this parasite kill? AB - BACKGROUND: Severe disease attributable to Plasmodium vivax infection is already well described worldwide; however, autopsies in these patients are scarce. METHODS: From 1996 to 2010, 19 patient deaths with a clinical diagnosis of P. vivax infection occurred in a tertiary care center in the Brazilian Amazon. Seventeen of these 19 deaths were fully autopsied. Clinical charts, macroscopic autopsy reports, and stored paraffinized tissue blocks were retrieved. Nested polymerase chain reaction was performed in paraffinized samples of spleen and lung to confirm P. vivax monoinfection. Immunohistofluorescence was used to detect P. vivax parasitized red blood cells (RBCs). RESULTS: Of 17 autopsies, 13 revealed that death could be attributed to P. vivax infection; in the remaining 4, acute diseases other than malaria were found to be the cause of death. The primary complication in patients in which malaria contributed to death was acute respiratory distress syndrome (ARDS) and pulmonary edema associated with the accumulation of neutrophils in the interalveolar space (6 cases). Spleen rupture (3 cases) and multiorgan dysfunction syndrome (3 cases) were the second most common complications. One child evolving with coma was also characterized, but no parasite was detected in the brain tissue. In one patient who developed ARDS and presented negative peripheral parasitemia by the time of death, scattered parasitized red blood cells were seen inside pulmonary capillaries, suggesting some sequestration in the lung. CONCLUSIONS: In 13 of 17 deceased patients, P. vivax infection was the plausible cause of death. However, more studies are needed to understand pathogenesis related to severe disease. PMID- 22772804 TI - The interaction of flavonoid-lysozyme and the relationship between molecular structure of flavonoids and their binding activity to lysozyme. AB - In this work, the interactions of twelve structurally different flavonoids with Lysozyme (Lys) were studied by fluorescence quenching method. The interaction mechanism and binding properties were investigated. It was found that the binding capacities of flavonoids to Lys were highly depend on the number and position of hydrogen, the kind and position of glycosyl. To explore the selectivity of the bindings of flavonoids with Lys, the structure descriptors of the flavonoids were calculated under QSAR software package of Cerius2, the quantitative relationship between the structures of flavonoids and their binding activities to Lys (QSAR) was performed through genetic function approximation (GFA) regression analysis. The QSAR regression equation was K(A) = 37850.460 + 1630.01Dipole +3038.330HD 171.795MR. (r = 0.858, r(CV)(2) = 0.444, F((11,3)) = 7.48), where K(A) is binding constants, Dipole, HD and MR was dipole moment, number of hydrogen-bond donor and molecular refractivity, respectively. The obtained results make us understand better how the molecular structures influencing their binding to protein which may open up new avenues for the design of the most suitable flavonoids derivatives with structure variants. PMID- 22772805 TI - Synthesis and photophysical properties of yellow-emitting iridium complexes. Effect of the temperature on the character of triplet emission. AB - The parent study includes synthesis end photophysical characterization of four new phosphorescent cyclometalated iridium (III) complexes. The cyclometaled ligands used here are 2-(4-chlorophenyl)benzo[d]thiazole, 2(4isopropylphenyl)benzo[d] thiazole, 2-(4-methoxyphenyl)benzo[d]thiazole, 4 (benzo[d]thiazol-2-yl)-N,N-dimethylaniline. The auxiliary ligand is acetylacetone (Hacac). The photometric analyses show temperature dependence on phosphorescent spectra and the nature of the emitting state of the synthesized complexes. Using fluorescent and absorption spectroscopy we suggest an explanation of the observed effect points out the transition from ligand centered (LC) to MLCT main character of the emitting state. The quantitative photometric analysis states high phosphorescent quantum yields of the complexes in solution. PMID- 22772806 TI - Origin of the directed movement of protocells in the early stages of the evolution of life. AB - The origin of the directed motion of protocells during the early stages of evolution was discussed. The expenditures for movement, space orientation, and reception of information about the environment were taken into consideration, and it was shown that directed movement is evolutionarily advantageous in the following cases: when opposite gradients of different resources (for example, matter and energy) are great enough and when there is a rapid change in environmental parameters. It was also shown that the advantage of directed movement strategies depends greatly on how information about the environment is obtained by a protocell. PMID- 22772807 TI - Platelet count/spleen diameter ratio: is there sufficient evidence for its use? PMID- 22772808 TI - Co-cultured endometrial stromal cells and peritoneal mesothelial cells for an in vitro model of endometriosis. AB - This paper demonstrates an in vitro model to simulate the microenvironment of endometriosis. We used microfluidic channels with cover slips to pattern and release endometrial stromal cells (ESCs) and human peritoneal mesothelial cells (HPMCs) in a way that mimicked the pathophysiology of peritoneal endometriosis. This approach enabled observation in real time interactions between ESCs and HPMCs both in their normal and pathological states. HPMCs from control individuals were able to resist the invasion of ESCs from both control and endometriotic individuals. By contrast, HPMCs from endometriotic individuals were unable to resist the invasion of ESCs from both normal and endometriotic individuals. We further analyzed the dynamics between HPMCs and ESCs from endometriotic individuals. HPMCs from endometriotic individuals relaxed their adhesion to each other at the beginning of invasion of ESCs, lose their adhesion to the substrate and apoptosed when surrounded by ESCs. These data implicate that the peritoneal physiology may play an important role in endometriosis. PMID- 22772809 TI - Effect of cross-linking and enzymatic hydrolysis composite modification on the properties of rice starches. AB - Native rice starch lacks the versatility necessary to function adequately under rigorous industrial processing, so modified starches are needed to meet the functional properties required in food products. This work investigated the impact of enzymatic hydrolysis and cross-linking composite modification on the properties of rice starches. Rice starch was cross-linked with epichlorohydrin (EPI) with different concentrations (0.5%, 0.7%, 0.9% w/w, on a dry starch basis), affording cross-linked rice starches with the three different levels of cross-linking that were named R1, R2, and R3, respectively. The cross-linked rice starches were hydrolyzed by alpha-amylase and native, hydrolyzed, and hydrolyzed cross-linked rice starches were comparatively studied. It was found that hydrolyzed cross-linked rice starches showed a lower the degree of amylase hydrolysis compared with hydrolyzed rice starch. The higher the degree of cross linking, the higher the capacity to resist enzyme hydrolysis. Hydrolyzed cross linked rice starches further increased the adsorptive capacities of starches for liquids and decreased the trend of retrogradation, and it also strengthened the capacity to resist shear compared to native and hydrolyzed rice starches. PMID- 22772810 TI - Evaluation of black tea polyphenol extract against the retrogradation of starches from various plant sources. AB - The effects of black tea polyphenol extract (BTPE) on the retrogradation of starches from different plant sources were studied using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). DSC analysis shows that the gelatinization temperature of maize starch and starches from different rice varieties increased with increasing BTPE level. After storage at 4 degrees C, BTPE at a concentration of 15% markedly retarded the retrogradation of maize starch and starches from different rice varieties. Native maize starch and starches from different rice varieties showed typical A-type X-ray diffraction patterns, while native potato starch showed a typical B-type X-ray diffraction pattern. Adding BTPE significantly affected the crystalline region and intensities of X-ray diffraction peaks of maize and rice starch granules. It is concluded that adding BTPE markedly inhibits the retrogradation of maize starch and starches from different rice varieties, but has no significant influence on the gelatinization and retrogradation characteristics of potato starch. PMID- 22772811 TI - p-Cymene protects mice against lipopolysaccharide-induced acute lung injury by inhibiting inflammatory cell activation. AB - The objective of this study was to test the hypothesis that p-cymene can attenuate acute lung injury induced by lipopolysaccharide (LPS) in vivo. In the mouse model of LPS-induced acute lung injury, intraperitoneal preconditioning with p-cymene resulted in a significant reduction of pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6), lung water gain, inflammatory cell infiltration, lung tissue myeloperoxidase activity. In addition, p-cymene blocked the phosphorylation of IkappaBalpha protein and mitogen-activated protein kinases (MAPK) signaling pathway activation. Histopathologic examination of lung tissue indicated that p-cymene treatment markedly decreased focal thickening, congestion, pulmonary edema, and inflammatory cells infiltration. The results showed that p-cymene had a protective effect on LPS-induced ALI in mice. PMID- 22772812 TI - Synthesis and fungicidal activity of novel 2,3-disubstituted-1,3-benzoxazines. AB - A series of new 2,3-disubstituted-3,4-dihydro-2H-1,3-benzoxazines were prepared in moderate to excellent yields by aza-acetalizations of aromatic aldehydes with 2-(N-substituted aminomethyl)phenols in the presence of TMSCl. Their structures were confirmed by IR, 1H-NMR, 13C-NMR, MS and elemental analysis. The fungicidal activities of the target compounds were preliminarily evaluated, and some compounds exhibited good activity against Rhizoctonia solani. PMID- 22772813 TI - Branched ZnO nanostructures as building blocks of photoelectrodes for efficient solar energy conversion. AB - ZnO nanotetrapods are distinguished by their unique nanocrystalline geometric form with four tetrahedrally directed arms, which endows them the ability to handily assemble three-dimensional network structures. Such network structures, coupled with the intrinsically excellent electronic properties of the semiconducting ZnO, have proved advantageous for building photoelectrodes in energy conversion devices since they allow fast vectorial electron transport. In this review article, we summarize recent efforts, with partial emphasis on our own, in the development of ZnO nanotetrapod-based devices for solar energy conversion, including dye-sensitized solar cells and photoelectrochemical cells for water splitting. A pure ZnO nanotetrapod network was firstly demonstrated to have excellent charge collection properties even with just physical contacts. Composition design of ZnO nanotetrapods/SnO(2) nanoparticles yielded a high efficiency of 4.91% in flexible DSSCs. More significantly, by secondary branching and nitrogen doping, a record performance for water splitting has been achieved. A perspective on future research directions in ZnO nanotetrapod-based solar energy conversion devices is also discussed together with possible strategies of pursuit. It is hoped that the results obtained so far with the ZnO nanotetrapods could inspire and catalyze future developments of solar energy conversion systems based on branched nanostructural materials, contributing to solving global energy and environmental issues. PMID- 22772815 TI - Synthesis of graphene nanosheets with good control over the number of layers within the two-dimensional galleries of layered double hydroxides. AB - Graphene nanosheets have been generated in the confined space of the two dimensional galleries of a layered double hydroxide (LDH) and good control over the number of graphene layers can be achieved by adjusting the amounts of intercalated carbon source. PMID- 22772814 TI - Multilocus definition of MHC haplotypes in pedigreed cynomolgus macaques (Macaca fascicularis). AB - Cynomolgus macaques (Macaca fascicularis) are used widely in biomedical research, and the genetics of their MHC (Mhc-Mafa) has become the focus of considerable attention in recent years. The cohort of Indonesian pedigreed macaques that we present here was typed for Mafa-A, -B, and -DR, by sequencing, as described in earlier studies. Additionally, the DRB region of these animals was characterised by microsatellite analyses. In this study, full-length sequencing of Mafa-DPA/B and -DQA/B in these animals was performed. A total of 75 different alleles were observed; 22 of which have not previously been reported, plus 18 extended exon 2 alleles that were already known. Furthermore, two microsatellites, D6S2854 and D6S2859, were used to characterise the complex Mafa-A region. Sequencing and segregation analyses revealed that the length patterns of these microsatellites are unique for each Mafa-A haplotype. In this work, we present a pedigreed colony of approximately 120 cynomolgus macaques; all of which are typed for the most significant polymorphic MHC class I and class II markers. Offspring of these pedigreed animals are easily characterised for their MHC by microsatellite analyses on the Mafa-A and -DRB regions, which makes the cumbersome sequencing analyses redundant. PMID- 22772816 TI - Descemet stripping automated endothelial keratoplasty for microcornea. AB - PURPOSE: Our aim was to evaluate the surgical technique and postoperative results of Descemet stripping automated endothelial keratoplasty (DSAEK) for bullous keratopathy in eyes with microcornea. METHODS: Two patients with microcornea (8.8 mm in case 1 and 9.3 mm in case 2) and bullous keratopathy after cataract surgery or after laser iridotomy were treated by DSAEK. A donor lamella with a smaller diameter (7.5 mm) was inserted into the anterior chamber using the double-glide donor insertion technique (Busin glide with intraocular lens sheet glide). RESULTS: No intraoperative or postoperative complications occurred. Corrected visual acuity improved from counting fingers to 0.222 logMAR in case 1 and from 1.000 to 0.155 logMAR in case 2 over 6 months. Corneal endothelial cell loss was 6.5 % in case 1 and 1.9 % in case 2. CONCLUSIONS: DSAEK was useful for bullous keratopathy in patients with microcornea. However, surgery should be done with meticulous care, and modification of the diameter of the donor lamella and of the donor insertion technique may be required. PMID- 22772818 TI - Smoking in early and mid-adolescence. AB - OBJECTIVE: Smoking among young people is declining in many European countries, although in some (particularly Central and Eastern Europe), the rates among young females are increasing. We compared the risk factors and variables for smoking in early- versus mid-adolescence with a view to helping policy makers identify age specific prevention strategies. METHODS: An anonymous questionnaire on smoking habits was administered to 1383 underage students in the Veneto Region (northeast Italy) in 2010, consisting of multiple-choice questions using words, numbers, and graphical illustrations designed to make it appeal to the adolescent age group. RESULTS: Among 611 sixth-grade students, 93.5% of the boys and 95.3% of the girls had never smoked, although this was true of 53.2% of the boys and only 38.8% of the girls among 772 ninth-grade students. The first cigarette was smoked in different social settings and places, depending on the adolescents' age group. Age also influenced how much adolescents approved of smoking and their perception of how much their parents approved of them smoking. Adherence to the rules of their group of friends was the only variable found associated with smoking in both the age groups considered. CONCLUSION: We found experimental or habitual cigarette smoking rare among sixth graders, but much more common among ninth graders. Focused preventive measures are therefore needed in the intervening years. The transition from middle school to higher education coincides with a sharp drop in the perceived regulation of smoking at school, emphasizing the need for action to establish high schools as smoke-free environments. PMID- 22772817 TI - Association of coronary atherosclerotic burden with clinical presentation and prognosis in patients with stable and unstable coronary artery disease. AB - BACKGROUND: The impact of coronary atherosclerotic burden on prognosis and presentation of patients with coronary artery disease (CAD) is unknown. We investigated the association of coronary atherosclerotic burden with clinical outcome and presentation as unstable angina in patients with CAD. METHODS: This study included 10,647 patients with stable (n = 8,149) and unstable (n = 2,498) CAD who underwent percutaneous coronary intervention (PCI). Coronary atherosclerotic burden was assessed by Gensini score. The primary outcome analysis was 1-year mortality. RESULTS: Patients were divided into groups according to quartiles of Gensini score: <13 (first quartile; n = 2,650 patients), 13 to <25 (second quartile; n = 2,611 patients), 25 to <53 (third quartile; n = 2,721 patients) and >= 53 (fourth quartile; n = 2,665 patients). There were 295 deaths during follow-up: 41 deaths in the first quartile, 42 deaths in the second quartile, 83 deaths in the third quartile and 129 deaths in the fourth quartile of Gensini score (Kaplan-Meier estimates of 1-year mortality 1.6, 1.7, 3.1 and 5.0 %, respectively; adjusted hazards ratio [HR] = 1.08, 95 % confidence interval [CI] 1.02-1.14, P = 0.007 for each 20-point increase in Gensini score). Gensini score was an independent correlate of presentation as unstable angina (adjusted odds ratio [OR] = 1.07, 95 % CI 1.05-1.10, P < 0.001, for each 20-point increase in the score). Coronary stenoses with >= 75 % of lumen obstruction mediated almost all the increased risk related to the atherosclerotic burden for presentation as unstable CAD (adjusted OR = 1.08, 95 % CI 1.05-1.12, P < 0.001). CONCLUSION: In patients with CAD, coronary atherosclerotic burden is independently associated with increased risk of 1-year mortality and presentation as unstable angina. PMID- 22772819 TI - Longitudinal study of emerging mental health concerns in youth perinatally infected with HIV and peer comparisons. AB - OBJECTIVE: Cross-sectional research indicates high rates of mental health concerns among youth with perinatal HIV infection (PHIV), but few studies have examined emerging psychiatric symptoms over time. METHODS: Youth with PHIV and peer comparisons who were HIV-exposed but uninfected or living in households with HIV-infected family members (HIV-affected) and primary caregivers participated in a prospective, multisite, longitudinal cohort study. Groups were compared for differences in the incidence of emerging psychiatric symptoms during 2 years of follow-up and for differences in psychotropic drug therapy. Logistic regression models were used to evaluate the association of emerging symptoms with HIV status and psychosocial risk factors. RESULTS: Of 573 youth with study entry assessments, 92% attended at least 1 annual follow-up visit (PHIV: 296; comparisons: 229). A substantial percentage of youth who did not meet symptom criteria for a psychiatric disorder at study entry did so during follow-up (PHIV = 36%; comparisons = 42%). In addition, those who met criteria at study entry often met criteria during follow-up (PHIV = 41%; comparisons = 43%). Asymptomatic youth with PHIV were significantly more likely to receive psychotropic medication during follow-up than comparisons. Youth with greater HIV disease severity (entry CD4% <25% vs 25% or more) had higher probability of depression symptoms (19% vs 8%, respectively). CONCLUSIONS: Many youth in families affected by HIV are at risk for development of psychiatric symptoms. PMID- 22772821 TI - Unmet developmental, behavioral, and psychosocial needs in children attending pediatric outpatient clinics. AB - OBJECTIVE: In this study of children attending general pediatric hospital outpatient clinics, we aimed to examine the proportion of (1) children with developmental and behavioral concerns; (2) parents with mental health problems; and (3) families with less than adequate psychosocial resources. We were also interested in the extent to which pediatricians discussed these problems with parents. METHODS: This was a cross-sectional study of families with children aged 4 to 8 years attending pediatric outpatient clinics at the Royal Children's Hospital, Melbourne. The Strengths and Difficulties Questionnaire, Parents' Evaluation of Developmental Status, Kessler-6 Scale for Psychological Distress, and Family Resource Scale were administered postvisit to assess development and behavior, parental mental health, and psychosocial resources. Parents were asked whether these issues were discussed during the consultation. RESULTS: A total of 162 families participated. Behavioral concerns were identified in 26% of children and concerns about language and motor development in 24% and 11%, respectively. Only 39% of consultations included discussion about development and 46% about behavior. Almost two-thirds (64%) of families reported less than adequate psychosocial resources, yet fewer than 10% of consultations included discussion of this, and only 7% addressed parental mental health. Parental perception of reasons why concerns were not discussed included "not relevant" (47%) and "the doctor did not bring it up" (21%). Only 2% of parents "didn't want to discuss the concern." CONCLUSIONS: A high proportion of children and families attending pediatric outpatients have unidentified concerns in development and/or behavior, and parents have mental health or psychosocial issues; these concerns are often not discussed, and thus opportunities for timely intervention are missed. PMID- 22772822 TI - Association between television viewing and self-esteem in children. AB - OBJECTIVE: Few studies have examined the effect of excess television (TV) viewing on specific mental health outcomes, such as self-esteem. We explored the cross sectional association between TV viewing hours and self-esteem in young children. METHODS: A total of 70,210 primary 4 (US grade 4) participants of the Department of Health Student Health Service, Hong Kong, in 1998-2000 reported TV viewing hours in a standardized questionnaire. Self-esteem was assessed using the Culture Free Self-Esteem Inventories for Children (SEI) with 4 subscales. Multivariate linear regression yielded beta coefficients (beta) for SEI subscale scores by TV hours, adjusting for age, sex, body mass index, lifestyle characteristics, and highest parental education and occupational status. RESULTS: Only 10.9% of children watched >4 hours per day, while 45.3% watched TV for 1 to <=2 hours per day. Compared with children who watched <1 hour of TV per day, those who watched a moderate amount (1 to <=2 hours/day) had higher (more favorable) SEI scores in the General (beta = 0.09; 95% confidence interval = 0.02-0.16), Social (0.05; 0.01-0.09), and Parent-Related (0.04; 0.00-0.08) subscales but lower scores in the Academic subscale (-0.06; -0.09 to -0.02). Children who watched >2 hours of TV per day had lower SEI scores than those who watched <1 hour per day in all 4 subscales. CONCLUSIONS: An inverted J-shaped relation was observed between TV viewing hours and self-esteem among young children. The development of self esteem among children who report little or excessive TV viewing should be further studied. PMID- 22772823 TI - Parenting style, parenting stress, and children's health-related behaviors. AB - OBJECTIVE: Parental guidance is critical to the development of children's health related behaviors. The purpose of this study was to look at the relationship between parenting factors, including parenting style and parenting stress, and children's health-related behaviors. METHODS: In this descriptive, correlational study, 284 parents of preschool children were interviewed using the Child Rearing Questionnaire and the Korean Parenting Stress Index-Short Form. RESULTS: Parent distress, authoritative and permissive parenting styles, family income, and mother's education were significantly associated with children's health-related behaviors. CONCLUSIONS: These findings suggest that higher levels of warmth, characteristics of both parenting styles, may be a critical factor in the development of health-related behaviors. PMID- 22772828 TI - Non-covalent interactions - QTAIM and NBO analysis. AB - MP2(full)/6-311++G(3df,3pd) calculations were carried out on complexes linked through various non-covalent Lewis acid - Lewis base interactions. These are: hydrogen bond, dihydrogen bond, hydride bond and halogen bond. The quantum theory of 'atoms in molecules' (QTAIM) as well as the natural bond orbitals (NBO) method were applied to analyze properties of these interactions. It was found that for the A-H...B hydrogen bond as well as for the A-X...B halogen bond (X designates halogen) the complex formation leads to the increase of s-character in the A-atom hybrid orbital aimed toward the H or X atom. In opposite, for the A...H-B hydride bond, where the H-atom possesses negative charge, the decrease of s-character in the B-atom orbital is observed. All these changes connected with the redistribution of the electron charge being the effect of the complex formation are in line with Bent's rule. The numerous correlations between energetic, geometrical, NBO and QTAIM parameters were also found. PMID- 22772829 TI - An atomistic-based chemophysical environment for evaluating asphalt oxidation and antioxidants. AB - Asphalt binders in service conditions are subject to oxidative aging that involves the reactions between oxygen molecules and the component species of bulk asphalt. As a result, significant alterations can occur to the desired physical and/or mechanical properties of asphalt. A common practice to alleviate asphalt aging has been to employ different chemical additives or modifiers as antioxidants. The current state of knowledge in asphalt oxidation and antioxidant evaluation is centered on determining the degradation of asphalt physical properties, mainly the viscosity and ductility. Such practices, although meeting direct engineering needs, do not contribute to the fundamental understanding of the aging and anti-oxidation mechanisms, and thereby developing anti-aging strategies. From this standpoint, this study was initiated to study the chemical and physical bases of asphalt oxidation, as well as the anti-oxidation mechanisms of bio-based antioxidants using the coniferyl-alcohol lignin as an example. A quantum chemistry (QC) based chemophysical environment is developed, in which the various chemical reactions between asphalt component species and oxygen, as well as the incurred physical changes are studied. X-ray photoelectron spectroscopy (XPS) was used to validate the modified and unmodified asphalt models. PMID- 22772830 TI - The diverse constructs use of activities of daily living measures in stroke randomized controlled trials in the years 2005-2009. AB - OBJECTIVE: To explore construct(s) (ability, capability, actual performance, and/or perceived difficulty) of activities of daily living measures that have been used in randomized controlled trials. METHODS: Three databases (Medline, CINAHL, and OTSeeker) were searched. A questionnaire was sent to the author of each eligible study requesting information about the activities of daily living construct(s) that were adopted in his/her study. RESULTS: A total of 106 studies, which altogether used 17 different activities of daily living measures, were found. Among these, only 12 studies specified in the paper the activities of daily living construct assessed; 7 studies assessed "ability" and 5 assessed "actual performance". Only 20% of the randomized controlled trials authors reported the mode of administration in the paper. Authors of 34 studies replied to our questionnaire. The most commonly used activities of daily living measures (i.e. the Barthel Index (either the 0-20 or 0-100 scoring version) and the Functional Independence Measure) were employed for assessing various constructs of activities of daily living, with inconsistency between the studies. CONCLUSION: In stroke randomized controlled trials that measured activities of daily living as an outcome, the measures were used for assessing various construct(s) of activities of daily living (including ability, capability, actual performance, and/or perceived difficulty). This could hamper data interpretation, meta-analysis, and the translation of evidence into clinical practice. PMID- 22772831 TI - Automatic generation of anatomic characteristics from cerebral aneurysm surface models. AB - PURPOSE: Computer-aided research on cerebral aneurysms often depends on a polygonal mesh representation of the vessel lumen. To support a differentiated, anatomy-aware analysis, it is necessary to derive anatomic descriptors from the surface model. We present an approach on automatic decomposition of the adjacent vessels into near- and far-vessel regions and computation of the axial plane. We also exemplarily present two applications of the geometric descriptors: automatic computation of a unique vessel order and automatic viewpoint selection. METHODS: Approximation methods are employed to analyze vessel cross-sections and the vessel area profile along the centerline. The resulting transition zones between near- and far- vessel regions are used as input for an optimization process to compute the axial plane. The unique vessel order is defined via projection into the plane space of the axial plane. The viewing direction for the automatic viewpoint selection is derived from the normal vector of the axial plane. RESULTS: The approach was successfully applied to representative data sets exhibiting a broad variability with respect to the configuration of their adjacent vessels. A robustness analysis showed that the automatic decomposition is stable against noise. A survey with 4 medical experts showed a broad agreement with the automatically defined transition zones. CONCLUSION: Due to the general nature of the underlying algorithms, this approach is applicable to most of the likely aneurysm configurations in the cerebral vasculature. Additional geometric information obtained during automatic decomposition can support correction in case the automatic approach fails. The resulting descriptors can be used for various applications in the field of visualization, exploration and analysis of cerebral aneurysms. PMID- 22772832 TI - Organochlorine pesticide residues in human blood samples collected from Haryana, India and the changing pattern. AB - Blood samples were collected during August 1992 and August 2002 from various hospitals of Haryana state and analyzed for the presence of HCH and DDT residues and the change in concentration of pesticide residues was calculated in terms of % reduction. The study revealed that the mean residue levels of total HCH in human blood samples have declined by 87.6% while those of total DDT have decreased by 98.9% during a gap of 10 years. The obtained results reveal that during 1992 p,p'-DDT was the major component with the mean value of 6.125 mg/L followed by p,p'-DDE, gamma-HCH, alpha-HCH and beta-HCH while in 2002, beta-HCH and p,p'-DDE were comparable with mean value of 0.053 and 0.052 mg/L, respectively followed by p,p'-DDT, alpha-HCH and p,p'-DDD. PMID- 22772833 TI - Construction of a photochemical reactor combining a CCD spectrophotometer and a LED radiation source. AB - An inexpensive photoreactor using LED light sources and a fibre-optic CCD spectrophotometer as a detector was built by designing a special cell holder for standard 1.000 cm cuvettes. The use of this device was demonstrated by studying the aqueous photochemical reaction of 2,5-dichloro-1,4-benzoquinone. The developed method combines the highly quantitative data collection of CCD spectrophotometers with the possibility of illuminating the sample independently of the detecting light beam, which is a substantial improvement of the method using diode array spectrophotometers as photoreactors. PMID- 22772834 TI - Non-invasive diagnosis of lung tuberculosis in children by single voxel 1H magnetic resonance spectroscopy. AB - Our previous study showed that (1)H-magnetic resonance spectroscopy ((1)H-MRS) can detect lipid peaks characteristic for Mycobacterium tuberculosis infection in cerebral lesions of young children; therefore, we aimed to extend and validate the application of (1)H-MRS for the diagnosis of active pulmonary tuberculosis lesions in three adolescent patients. Here, we document lipid peaks characteristic for M. tuberculosis infection by (1)H-MRS from lung tissue surrounding lung cavities of two patients whose sputum samples were positive for acid-fast bacilli by microscopy and positive for M. tuberculosis by genetic testing, indicating active tuberculosis. A similar lipid peak was found also in the pleural effusion of a third patient with concurrent lung cavity compatible with active tuberculosis. However, in a patient with a pyogenic pulmonary abscess, (1)H-MRS of the drained pus displayed different characteristic peaks but no lipid peak at all. CONCLUSION: Our findings further validate (1)H-MRS as a rapid, non-invasive, and specific diagnostic tool for active tuberculosis in children with microbiologically documented infection outside the central nervous system, specifically in the lungs. PMID- 22772835 TI - Functional assignment of metagenomic data: challenges and applications. AB - Metagenomic sequencing provides a unique opportunity to explore earth's limitless environments harboring scores of yet unknown and mostly unculturable microbes and other organisms. Functional analysis of the metagenomic data plays a central role in projects aiming to explore the most essential questions in microbiology, namely 'In a given environment, among the microbes present, what are they doing, and how are they doing it?' Toward this goal, several large-scale metagenomic projects have recently been conducted or are currently underway. Functional analysis of metagenomic data mainly suffers from the vast amount of data generated in these projects. The shear amount of data requires much computational time and storage space. These problems are compounded by other factors potentially affecting the functional analysis, including, sample preparation, sequencing method and average genome size of the metagenomic samples. In addition, the read-lengths generated during sequencing influence sequence assembly, gene prediction and subsequently the functional analysis. The level of confidence for functional predictions increases with increasing read-length. Usually, the most reliable functional annotations for metagenomic sequences are achieved using homology-based approaches against publicly available reference sequence databases. Here, we present an overview of the current state of functional analysis of metagenomic sequence data, bottlenecks frequently encountered and possible solutions in light of currently available resources and tools. Finally, we provide some examples of applications from recent metagenomic studies which have been successfully conducted in spite of the known difficulties. PMID- 22772836 TI - Ultrafast clustering algorithms for metagenomic sequence analysis. AB - The rapid advances of high-throughput sequencing technologies dramatically prompted metagenomic studies of microbial communities that exist at various environments. Fundamental questions in metagenomics include the identities, composition and dynamics of microbial populations and their functions and interactions. However, the massive quantity and the comprehensive complexity of these sequence data pose tremendous challenges in data analysis. These challenges include but are not limited to ever-increasing computational demand, biased sequence sampling, sequence errors, sequence artifacts and novel sequences. Sequence clustering methods can directly answer many of the fundamental questions by grouping similar sequences into families. In addition, clustering analysis also addresses the challenges in metagenomics. Thus, a large redundant data set can be represented with a small non-redundant set, where each cluster can be represented by a single entry or a consensus. Artifacts can be rapidly detected through clustering. Errors can be identified, filtered or corrected by using consensus from sequences within clusters. PMID- 22772837 TI - A comparative analysis of biclustering algorithms for gene expression data. AB - The need to analyze high-dimension biological data is driving the development of new data mining methods. Biclustering algorithms have been successfully applied to gene expression data to discover local patterns, in which a subset of genes exhibit similar expression levels over a subset of conditions. However, it is not clear which algorithms are best suited for this task. Many algorithms have been published in the past decade, most of which have been compared only to a small number of algorithms. Surveys and comparisons exist in the literature, but because of the large number and variety of biclustering algorithms, they are quickly outdated. In this article we partially address this problem of evaluating the strengths and weaknesses of existing biclustering methods. We used the BiBench package to compare 12 algorithms, many of which were recently published or have not been extensively studied. The algorithms were tested on a suite of synthetic data sets to measure their performance on data with varying conditions, such as different bicluster models, varying noise, varying numbers of biclusters and overlapping biclusters. The algorithms were also tested on eight large gene expression data sets obtained from the Gene Expression Omnibus. Gene Ontology enrichment analysis was performed on the resulting biclusters, and the best enrichment terms are reported. Our analyses show that the biclustering method and its parameters should be selected based on the desired model, whether that model allows overlapping biclusters, and its robustness to noise. In addition, we observe that the biclustering algorithms capable of finding more than one model are more successful at capturing biologically relevant clusters. PMID- 22772838 TI - Photocatalytic hydrogen production from a simple water-soluble [FeFe]-hydrogenase model system. AB - Combined with a simple water soluble [FeFe]-hydrogenase mimic 1, Ru(bpy)(3)(2+) and ascorbic acid enable hydrogen production photocatalytically. More than 88 equivalents of H(2) were achieved in water, which is much better than that obtained in an organic solvent or a mixture of organic solvent and water. PMID- 22772839 TI - Thumbs up sign in brain death. AB - INTRODUCTION: Spinal reflexes can be seen in the setting of brain death. We present a new spinal reflex. We also review spinal movements in pediatric brain death and provide suggestions to distinguish them from movements generated by the brain. CASE REPORT: We report a five-year old girl admitted after an asystolic cardiac arrest and was soon declared brain death as a result of bilateral cerebellar hematoma. She had spinal movements including a "Thumbs up sign". These findings delayed organ procurement. CONCLUSION: "Thumbs up sign" should be added to the list of spinal reflexes seen with brain death. Spinal reflexes in brain death can be clinically recognized and should explained to all involved parties to avoid unnecessary testing, confusion for family members, and delay or refusal of organ donation. PMID- 22772840 TI - Rural veterans' perspectives of dual care. AB - The purpose of this study was to develop an in-depth understanding of the barriers and enablers of effective dual care (care obtained from the Veterans Health Administration [VHA] and the private health system) for rural veterans. Telephone interviews of a random sample of 1,006 veterans residing in rural Nebraska were completed in 2010. A high proportion of the rural veterans interviewed reported receiving dual care. The common reasons cited for seeking care outside the VHA (or VA [Veterans Administration]) included having an established relationship with a non-VA provider and distance to the nearest VA medical center. Almost half of the veterans who reported having a personal doctor or nurse reported that this was a non-VA provider. Veterans reported high levels of satisfaction with the quality of care they receive. Ordinal logistic regression models found that veterans who were Medicare beneficiaries, and who rated their health status higher had higher satisfaction with dual care. The reasons cited by the veterans for seeking care at the VHA (quality of VHA care, lower costs of VHA care, entitlement) and veterans perceptions about dual care (confused about where to seek care for different ailments, perceived lack of coordination between VA and non VA providers) were significant predictors of veterans' satisfaction with dual care. This study will guide policymakers in the VA to design a shared care system that can provide seamless, timely, high quality and veteran centered care. PMID- 22772841 TI - Resources, roadblocks and turning points: a qualitative study of American Indian/Alaska Native adults with type 2 diabetes. AB - Type 2 diabetes is a worldwide health problem that has reached epidemic proportions in some communities. Alaska Native and American Indian (AN/AI) people are disproportionately diagnosed with type 2 diabetes and incidence is increasing in many Alaska communities. Developing effective interventions requires understanding the social and psychological factors that impact effective management of diabetes, yet little is known about these factors in AN/AI communities. The objective of this study was to explore perceived psychosocial needs and barriers to management of diabetes among AN/AI adults with type 2 diabetes receiving care at the Alaska Native Primary Care Center (ANPCC) to inform programmatic efforts and potential future research. We conducted three focus groups and five interviews with 13 AN/AI adults with type 2 diabetes. Interview and focus group questions elicited perceived factors that affect management of diabetes, with a focus on the psychological, social and spiritual impacts of diabetes. Data were transcribed, coded and analyzed using thematic analysis. Key themes that emerged from these data included resources and roadblocks, as well as turning points in the trajectory of diabetes. Resources are factors with a perceived positive impact on management of diabetes, including: (1) knowledge and education about diabetes, (2) social support from other people with diabetes, (3) spirituality, and (4) self-efficacy. Roadblocks are factors with a perceived negative impact on management of diabetes and include: (1) self-reported lack of knowledge about nutrition and diet, (2) social difficulties caused by dietary restrictions, and (3) co-morbid medical conditions. Finally, turning points are experiences described by participants as having transformed roadblocks in resources and thus facilitating improvement in the management of diabetes. Future programmatic interventions to improve management of diabetes with this population should focus on improving dietary education and social support opportunities for newly-diagnosed individuals. Also, educational and support opportunities for family members and friends of individuals with diabetes should also be offered to facilitate understanding and support of their loved ones' management of diabetes, especially with regard to dietary restrictions in social settings. Efforts should also focus on strengthening newly-diagnosed individuals' self-efficacy and providing ongoing support as individuals progressively adjust to the illness over time and make behavioral changes. Future research with this population should explore the effects of family support groups and the possibility of Web-based or other alternative interventions for improving psychosocial health and management of diabetes efforts. PMID- 22772842 TI - HPV infection awareness and self-reported HPV vaccination coverage in female adolescent students in two German cities. AB - Low levels of human papillomavirus (HPV) awareness and knowledge have been observed in the few studies conducted among school-going adolescents. Such data are lacking in Germany. To assess awareness of HPV and of vaccination status among girls attending grades 8-13 in Bremen and Bremerhaven, two German cities. Participants completed a questionnaire in school including questions on demographic characteristics, about HPV awareness and on vaccination status. We analysed the relationship between awareness of HPV, of vaccination status and vaccine uptake and several variables including age and migrant background using univariate and multivariate logistic regression. Six hundred and thirty-two girls aged 12-20 years completed the questionnaire. 50 % had no awareness of HPV, 12 % reported being vaccinated against HPV and 57 % did not know whether or not they were vaccinated against HPV. In multivariate analyses, ever had sex was associated with awareness of HPV, and ever been to a gynaecologist with awareness of vaccination status. Our results may be an indication that female adolescents in Germany are not adequately informed and counselled about HPV and associated issues. PMID- 22772843 TI - When to inseminate: a dilemma for dairy farmers. PMID- 22772844 TI - Control of off-label use of medicines. PMID- 22772845 TI - Classical swine fever in Nepal. PMID- 22772851 TI - Important aspects in ventilator triggering: a nod to trigger reliability. PMID- 22772852 TI - Improved setup for intestinal intravital microscopy in mice - the "floating table". PMID- 22772853 TI - Does experience trump technology? The case of US guidance and CVC placement. PMID- 22772854 TI - Soft tissue depression at the iliac crest prominence: a new landmark for identifying the L4-L5 interspace. AB - BACKGROUND: One of the most common approaches to identifying the L4-L5 interspace is using the iliac crest as a landmark. We propose a new landmark to identify the L4-L5 interspace based on the soft tissue depression palpable at the iliac crest prominence. The aim of this study was to assess the reliability and time saving when using this new landmark compared to using the iliac crest to perform a lumbar plexus block. METHODS: Fifty-four patients scheduled for lower limb surgery were randomly allocated to have a lumbar plexus block performed using the iliac crest (Chayen's approach) or the soft tissue depression (Borghi's approach). The landmarks for both approaches were drawn on each patient prior to randomization (N.=27 per group). All the blocks were performed by an anesthesiologist familiar with both techniques using a nerve stimulator and 30 mL of 0.5% levobupivacaine. The time to achieve successful needle placement and the number of needle re-directions, as well as the onset time for the sensory and motor blockade, were recorded. RESULTS: All the blocks using Borghi's approach were performed successfully. With the Chayen's approach, there were 5 needle placement failures. The mean times to onset of a successful block after injection of the local anesthetic did not differ between the two groups: 17.8+/-3.9 min for the Chayen vs. 15.9+/-2.4 min for the Borghi's approach (P=0.14). However, the mean time to achieve correct needle placement was 7.6+/-3.2 min with the Chayen's approach compared to 5.1 (+/-2.6 SD) min with the Borghi's approach (P<0.01). The Chayen's approach also required a significantly higher median number of needle redirections (2 [inter-quartile range (IQR): 0-4] vs. 0 [IQR: 0-4], P<0.01). In obese patients (BMI >=30 kg/m(2)), the mean placement time was 10.5+/-1.7 min vs. 4.8+/-2.1 min (P<0.01), and median number of needle re-directions was 2.5 (IQR: 2 3) vs. 0.5 (IQR: 0-3) (P=0.04), with the Chayen and Borghi's approach, respectively. CONCLUSION: Use of the palpable soft tissue depression at the iliac crest prominence for performing a lumbar plexus block offered several potential advantages over the standard inter-iliac crest approach. PMID- 22772855 TI - How to prevent ventilator-induced lung injury? AB - The experimental evidence that ventilator could injure lungs through the application of excessive end-inspiratory volumes and transpulmonary pressures has led to major changes in the clinical management of patients suffering from the acute respiratory distress syndrome (ARDS). The prevention of ventilator-induced lung injury has become one of the main goals of current ventilator strategies for patients with ARDS as well as for patients with normal lungs that require mechanical ventilation. Tidal volume reduction allowed for a reduction in mortality that confirmed the clinical relevance of ventilator-induced lung injury. In contrast, strategies for setting positive end-expiratory pressure (PEEP) have been proposed but the optimal PEEP level remains unsettled. Considerable efforts have been made within the last decades to try to develop new ventilator strategies as well as pharmacological and mechanical measures in order to prevent VILI and further improve the outcome of ARDS patients. This review will strive to describe seminal experimental and clinical studies that aimed at preventing the development of VILI. PMID- 22772856 TI - Fever in sepsis. AB - Fever is a common symptom of sepsis usually believed to predict better survival. Experimental data suggest that body temperature elevation may slow micro-organism growth and enhance host immune responses. In patients with sepsis, however, the high energy cost of fever may exacerbate the life-threatening situation. Fever control is widely used in the ICU, mainly in patients with infections. The efficacy of antipyretic drugs in lowering body temperature remains uncertain, however, and all antipyretics have well known adverse effects. Surface cooling methods are efficient but require sedation to avoid the harmful effects of shivering. A recent controlled trial in patients with septic shock suggests that external cooling for fever control may diminish vasopressor requirements and improve early survival. In this review, we examine the benefits and risks of fever and of controlled normothermia. The fever control modalities that provide the best risk/benefit ratio in sepsis are discussed. PMID- 22772857 TI - New membranes for extracorporeal blood purification in septic conditions. AB - Severe sepsis and septic shock are still the leading cause of mortality and morbidity in the intensive care unit. The inflammatory response to infection is associated with an impressive, systemic release of pro- and anti-inflammatory mediators, which results in generalized endothelial damage, multiple organ failure and altered cellular immunological responsiveness. Over the last years, the substantial advances in the understanding of sepsis have led to the development of a large number of new approaches and technologies in the management of septic patients. Extracorporeal blood purification techniques using various membrane materials have been proposed to modulate multiple inflammatory mediators, and seem to be a potential adjuvant in the treatment of sepsis. However, the use of extracorporeal blood purification techniques during sepsis still remains controversial, thus precluding any definitive recommendations on the benefit of these methods. More data are needed to better recognize septic patients who are most likely to benefit from blood purification treatments, and clarify the optimal timing, duration, and number of applications of these techniques in the daily clinical practice. PMID- 22772859 TI - Respiratory mechanics at different PEEP level during general anesthesia in the elderly: a pilot study. AB - BACKGROUND: General anesthesia could imply that the closing capacity exceed the functional residual capacity. This phenomenon, associated with a reduction of maximal expiratory flow, could lead to expiratory flow limitation (EFL). The aim of our study was to verify 1) a new method of determining EFL during anesthesia (PEEP test); 2) if anesthesia could be associated with the development of EFL; 3) if the use a small amount of PEEP is able to reverse the possible negative effects of low lung volume ventilation. METHODS: Fifty two patients scheduled for abdominal surgery were prospectively randomized in: 1) group ZEEP, ventilated at PEEP 0 H(2)O and 2) group PEEP ventilated at PEEP 5 cm H2O. The presence of EFL was determined by the negative expiratory pressure (NEP) test the day before surgery and by the PEEP test during surgery. Data of respiratory mechanics were calculated at the beginning and at the end of anesthesia. RESULTS: 1) The PEEP test allows the detection of EFL; 2) anesthesia was associated with EFL: 8 patients developed EFL after induction. At the end of surgery, 7 more patients became flow limited in the group ZEEP, while only 1 in the group PEEP. The group ZEEP exhibited a marked decrease of expiratory flow and a worsening of respiratory mechanics at the end of surgery. CONCLUSION: The PEEP test allowed to verify that EFL during anesthesia is a valuable phenomenon. The use of 5 cmH(2)O of PEEP was helpful to prevent the deterioration of lung mechanics that occurs during surgery. PMID- 22772860 TI - A reorientation strategy for reducing delirium in the critically ill. Results of an interventional study. AB - BACKGROUND: A wide variability in the approach towards delirium prevention and treatment in the critically ill results from the dearth of prospective randomised studies. METHODS: We launched a two-stage prospective observational study to assess delirium epidemiology, risk factors and impact on patient outcome, by enrolling all patients admitted to our Intensive Care Unit (ICU) over a year. The first step - from January to June 2008 was the observational phase, whereas the second one from July to December 2008 was interventional. All the patients admitted to our ICU were recruited but those with pre-existing cognitive disorders, dementia, psychosis and disability after stroke were excluded from the data analysis. Delirium assessment was performed according with Confusion Assessment Method for the ICU twice per day after sedation interruption. During phase 2, patients underwent both a re-orientation strategy and environmental, acoustic and visual stimulation. RESULTS: We admitted a total of respectively 170 (I-ph) and 144 patients (II-ph). The delirium occurrence was significantly lower in (II-ph) 22% vs. 35% in (I-ph) (P=0.020). A Cox's Proportional Hazard model found the applied reorientation strategy as the strongest protective predictors of delirium: (HR 0.504, 95% C.I. 0.313-0.890, P=0.034), whereas age (HR 1.034, 95% CI: 1.013-1.056, P=0.001) and sedation with midazolam plus opiate (HR 2.145, 95% CI: 2.247-4.032, P=0.018) were negative predictors. CONCLUSION: A timely reorientation strategy seems to be correlated with significantly lower occurrence of delirium. PMID- 22772862 TI - Characterization of the motion of membrane proteins using high-speed atomic force microscopy. AB - For cells to function properly, membrane proteins must be able to diffuse within biological membranes. The functions of these membrane proteins depend on their position and also on protein-protein and protein-lipid interactions. However, so far, it has not been possible to study simultaneously the structure and dynamics of biological membranes. Here, we show that the motion of unlabelled membrane proteins can be characterized using high-speed atomic force microscopy. We find that the molecules of outer membrane protein F (OmpF) are widely distributed in the membrane as a result of diffusion-limited aggregation, and while the overall protein motion scales roughly with the local density of proteins in the membrane, individual protein molecules can also diffuse freely or become trapped by protein protein interactions. Using these measurements, and the results of molecular dynamics simulations, we determine an interaction potential map and an interaction pathway for a membrane protein, which should provide new insights into the connection between the structures of individual proteins and the structures and dynamics of supramolecular membranes. PMID- 22772861 TI - The purification of the Chlamydomonas reinhardtii chloroplast ClpP complex: additional subunits and structural features. AB - The ClpP peptidase is a major constituent of the proteolytic machinery of bacteria and organelles. The chloroplast ClpP complex is unusual, in that it associates a large number of subunits, one of which (ClpP1) is encoded in the chloroplast, the others in the nucleus. The complexity of these large hetero oligomeric complexes has been a major difficulty in their overproduction and biochemical characterization. In this paper, we describe the purification of native chloroplast ClpP complex from the green alga Chlamydomonas reinhardtii, using a strain that carries the Strep-tag II at the C-terminus of the ClpP1 subunit. Similar to land plants, the algal complex comprises active and inactive subunits (3 ClpP and 5 ClpR, respectively). Evidence is presented that a sub complex can be produced by dissociation, comprising ClpP1 and ClpR1, 2, 3 and 4, similar to the ClpR-ring described in land plants. Our Chlamydomonas ClpP preparation also contains two ClpT subunits, ClpT3 and ClpT4, which like the land plant ClpT1 and ClpT2 show 2 Clp-N domains. ClpTs are believed to function in substrate binding and/or assembly of the two heptameric rings. Phylogenetic analysis indicates that ClpT subunits have appeared independently in Chlorophycean algae, in land plants and in dispersed cyanobacterial genomes. Negative staining electron microscopy shows that the Chlamydomonas complex retains the barrel-like shape of homo-oligomeric ClpPs, with 4 additional peripheral masses that we speculate represent either the additional IS1 domain of ClpP1 (a feature unique to algae) or ClpTs or extensions of ClpR subunits. PMID- 22772863 TI - Construction and development of a mammalian cell-based full-length antibody display library for targeting hepatocellular carcinoma. AB - We present a detailed method for constructing a mammalian cell-based full-length antibody display library for targeting hepatocellular carcinoma. Two novel mammalian library vectors pcDNA3-CHm and pcDNA3-CLm were constructed that contained restriction enzyme sites NheI, ClaI and antibody constant domain. Mammalian expression vector pcDNA3-CHm contains IgG heavy-chain (HC) constant region and glycosylphosphatidylinositol anchor (GPI) that could be anchored full length antibodies on the surface of mammalian cells. GOLPH2 prokaryotic expression vector was carried out in Escherichia coli and purified by immobilized metal affinity chromatography. Variable domain of heavy-chain and variable domain of light-chain genes were respectively inserted into the vector pcDNA3-CHm and pcDNA3-CLm by ligation, and antibody libraries are displayed as whole IgG molecules on the cell surface by co-transfecting this HC-GPI with a light chain. By screening the cell library using magnetic beads and cell ELISA, the cell clone that displayed GOLPH2-specific antibodies on cell surfaces was identified. The mammalian cell-based antibody display library is a great potential application for displaying full-length functional antibodies of targeting hepatocellular carcinoma on the surface of mammalian cells. Anti-GOLPH2 display antibody was successfully isolated from the library. PMID- 22772864 TI - Two-step denaturing gradient gel electrophoresis (2S-DGGE), a gel-based strategy to capture full-length 16S rRNA gene sequences. AB - Obtaining full-length 16S rRNA gene sequences is important for generating accurate taxonomy assignments of bacteria, which normally is realized via clone library construction. However, the application of clone library has been hindered due to its limitations in sample throughput and in capturing minor populations (<1 % of total microorganisms). To overcome these limitations, a new strategy, two-step denaturing gradient gel electrophoresis (2S-DGGE), is developed to obtain full-length 16S rRNA gene sequences. 2S-DGGE can compare microbial communities based on its first-round DGGE profiles and generate partial 16S rRNA gene sequences (8-534 bp, Escherichia coli numbering). Then, strain-specific primers can be designed based on sequence information of bacteria of interest to PCR amplify their remaining 16S rRNA gene sequences (515-1541 bps, E. coli numbering). The second-round DGGE can confirm DNA sequence purity of these PCR products. Finally, the full-length 16S rRNA gene sequences can be obtained through combining the two partial DNA sequences. By employing 2S-DGGE, taxonomies of a group of dehalogenating bacteria have been assigned based on their full length 16S rRNA gene sequences, several of which existed in dehalogenating microcosms as minor populations. In all, 2S-DGGE can be utilized as a medium throughput method for taxonomic identification of interested/minor populations from single or multiple microbial consortia. PMID- 22772865 TI - Photo- and thermally induced coloration of a crystalline MOF accompanying electron transfer and long-lived charge separation in a stable host-guest system. AB - A new type of electron transfer (ET) system was built via the combination of a highly stable MOF host framework and methyl viologen guest molecule. The pi stacking arrangements adjust the distance between the D-A components, contributing to the formation of an ultra long-lived charge separated state in the photo/thermo dual stimuli-responsive complex. PMID- 22772866 TI - Dynamic doping and degradation in sandwich-type light-emitting electrochemical cells. AB - Photoluminescence spectroscopy has been performed in situ during device operation and after switch-off on ionic transition metal complex (iTMC)-based sandwich-type light-emitting electrochemical cells (LECs). It is demonstrated that the photoluminescence of the LECs decreases with increasing operating time. For operating times up to three hours the decline in photoluminescence is fully recoverable after switching off the bias. These results imply that doping of the iTMC layer is responsible, not only, for the turn-on of LECs but also for their lifetimes. PMID- 22772867 TI - Prognostic value of BRAF(V600) mutations in melanoma patients after resection of metastatic lymph nodes. AB - PURPOSE: BRAF (V600) mutations are frequent in melanomas, and BRAF(V600)-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of >=2 mm according to BRAF (V600) mutations and other previously reported prognostic criteria. METHODS: This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF (V600) mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60 % melanoma cells. RESULTS: BRAF mutations (p.V600E and p.V600K in 83 and 14 % of cases, respectively) were detected in 40 % of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3 %, with a median OS of 1.4 and 2.8 years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P = 0.005, hazard ratio 2.2, 95 % confidence interval 1.3-3.9) and BRAF status (P = 0.005, hazard ratio 1.9, 95 % confidence interval 1.2-3.1). CONCLUSIONS: BRAF (V600) status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies. PMID- 22772868 TI - Resection with en bloc removal of regional lymph node after endoscopic resection for T1 colorectal cancer. AB - BACKGROUND: Various guidelines suggest indications for performing additional colectomy with en bloc removal of regional lymph nodes after endoscopic resection for T1 colon cancer. The aim of this study was to evaluate the pathologic outcomes of patients with surgical treatment after endoscopic resection for T1 colorectal cancer. METHODS: We used data from 275 patients who had undergone curative resection for T1 colorectal cancer at a single institution between 1991 and 2009. We evaluated the rationale for additional surgical treatment after endoscopic resection performed on 68 of the 275 patients and the association between various clinicopathologic features and lymph node metastasis. RESULTS: The 5-year overall survival rate was 96.3 %. Reasons for additional surgical treatment included an endoscopic specimen with a pathologically positive margin (n = 20), lymphovascular invasion (n = 25), and submucosal invasion depth of >= 1,000 MUm (n = 23). When endoscopists failed to find macroscopic cancer residue during endoscopic resection, no pathologically residual cancer was found in the resected specimens. Histologic grade was an independent risk factor for lymph node metastasis (p = 0.028). In the absence of lymphovascular invasion, patients with well-differentiated T1 colorectal cancer did not have nodal involvement. CONCLUSIONS: Although the outcomes of patients with additional surgical treatment after endoscopic resection for T1 colorectal cancer were satisfactory, excessive and unnecessary treatments may have been performed. Additional surgical treatment after endoscopic resection for T1 colorectal cancer might be unnecessary for patients with well-differentiated adenocarcinoma and no lymphovascular invasion. PMID- 22772869 TI - The role for sentinel lymph node dissection after neoadjuvant chemotherapy in patients who present with node-positive breast cancer. AB - BACKGROUND: Sentinel lymph node (SLN) dissection has been investigated after neoadjuvant chemotherapy and has shown mixed results. Our objective was to evaluate SLN dissection in node-positive patients and to determine whether postchemotherapy ultrasound could select patients for this technique. METHODS: Between 1994 and 2010, 150 patients with biopsy proven axillary metastasis underwent SLN dissection after chemotherapy and 121 underwent axillary lymph node dissection (ALND). Clinicopathologic characteristics were analyzed before and after chemotherapy. Statistical analyses included Fisher's exact test for nodal response and multivariate logistic regression for factors associated with false negative events. RESULTS: Median age was 52 years. Median tumor size at presentation was 2 cm. The SLN was identified in 93 % (139/150). In 111 patients in whom a SLN was identified and ALND performed, 15 patients had a false-negative SLN (20.8 %). In the 52 patients with normalized nodes on ultrasound, the false negative rate decreased to 16.1 %. Multivariate analysis revealed smaller initial tumor size and fewer SLNs removed (<2) were associated with a false-negative SLN. There were 63 (42 %) patients with a pathologic complete response (pCR) in the nodes. Of those with normalized nodes on ultrasound, 38 (51 %) of 75 had a pCR. Only 25 (33 %) of 75 with persistent suspicious/malignant-appearing nodes had a pCR (p = 0.047). CONCLUSIONS: Approximately 42 % of patients have a pCR in the nodes after chemotherapy. Normalized morphology on ultrasound correlates with a higher pCR rate. SLN dissection in these patients is associated with a false negative rate of 20.8 %. Removing fewer than two SLNs is associated with a higher false-negative rate. PMID- 22772870 TI - Efficacy of S-pantoprazole 20 mg compared with pantoprazole 40 mg in the treatment of reflux esophagitis: a randomized, double-blind comparative trial. AB - BACKGROUND: S-isomer (S) pantoprazole is known to be more effective and less dependent on cytochrome 2C19 than R-isomer (R)-pantoprazole. AIM: The purpose of this study was to compare the efficacy and safety of S-pantoprazole 20 mg versus pantoprazole 40 mg for treatment of reflux esophagitis. METHODS: This multi center, double-blind, randomized trial enrolled patients with endoscopically documented reflux esophagitis. Patients were assigned to receive either 20 mg S pantoprazole or 40 mg pantoprazole once daily for 4 weeks. Endoscopy and symptoms were assessed after 4 weeks of treatment. In patients whose reflux esophagitis was not resolved at 4 weeks, treatment was extended to 8 weeks and symptoms were reassessed. Heartburn, chest pain, acid regurgitation, globus, and overall symptoms were rated. The primary efficacy endpoint was healing of esophagitis, and secondary endpoints were symptomatic and endoscopic improvement. RESULTS: Sixty-seven patients in the S-pantoprazole group (52 male, mean age 51 years) and 62 in the pantoprazole group (61 male, mean age 50 years) were analyzed per protocol. The healing rate of reflux esophagitis was 85 % at 4 weeks and 94 % at 8 weeks in the S-pantoprazole group, which did not differ from those in the pantoprazole group (84 and 97 %, respectively). After treatment, individual and overall gastroesophageal reflux disease (GERD) symptoms and esophagitis improved compared with baseline inflammation in both groups. Intergroup differences in symptoms and endoscopic healing were not significant. CONCLUSION: The efficacy and safety of 20 mg S-pantoprazole were comparable to those of 40 mg pantoprazole for treatment of reflux esophagitis and symptomatic improvement of GERD. PMID- 22772871 TI - Laparoscopic repair of incarcerated inguinal hernia. A safe and effective procedure to adopt in children. AB - BACKGROUND: The purpose of our retrospective study was to describe the efficacy and the advantages of laparoscopic approach to treat incarcerated inguinal hernia (IIH) in pediatric patients. METHODS: In a 2-year period, 601 children underwent a laparoscopic inguinal hernia repair, 46 (7.6 %) of them presented an IIH. Our study will be focused on these 46 patients: 30 boys and 16 girls (age range 1 month-8 years). RESULTS: Twenty-one/46 hernias (45.6 %) were reduced preoperatively and then operated laparoscopically (RH), 25/46 (54.4 %) were irreducible and they were operated directly in laparoscopy (IRH). We have no conversions in our series. The length of surgery in RH group was in median 23 min and in IRH group was in median 30 min. Hospital stay was variable between 6 h and 3 days (median 36 h).With a minimum follow-up of 14 months, we had 2/46 recurrences (4.3 %). CONCLUSION: The laparoscopic approach to IIH appears easy to perform from the technical point of view. The 3 main advantages of laparoscopic approach are that all edematous tissue are surgically bypassed and the cord structures are not touched; the reduction is performed under direct visual control, and above all, an inspection of the incarcerated organ is performed at the end of procedure. PMID- 22772873 TI - Current concepts in Parkinson's disease and other movement disorders. PMID- 22772872 TI - Functional characterization and axonal transport of quantum dot labeled BDNF. AB - Brain derived neurotrophic factor (BDNF) plays a key role in the growth, development and maintenance of the central and peripheral nervous systems. Exogenous BDNF activates its membrane receptors at the axon terminal, and subsequently sends regulation signals to the cell body. To understand how a BDNF signal propagates in neurons, it is important to follow the trafficking of BDNF after it is internalized at the axon terminal. Here we labeled BDNF with bright, photostable quantum dots (QD-BDNF) and followed the axonal transport of QD-BDNF in real time in hippocampal neurons. We showed that QD-BDNF was able to bind BDNF receptors and activate downstream signaling pathways. When QD-BDNF was applied to the distal axons of hippocampal neurons, it was observed to be actively transported toward the cell body at an average speed of 1.11 +/- 0.05 MUm s(-1). A closer examination revealed that QD-BDNF was transported by both discrete endosomes and multivesicular body-like structures. Our results showed that QD BDNF could be used to track the movement of exogenous BDNF in neurons over long distances and to study the signaling organelles that contain BDNF. PMID- 22772874 TI - Emerging therapies for Parkinson's disease. AB - PURPOSE OF REVIEW: The experimental therapeutics of Parkinson's disease are reviewed, highlighting the current pipeline of emerging therapeutic approaches. RECENT FINDINGS: This review includes novel approaches to dopaminergic drug delivery such as intraintestinal infusions or new extended-release formulations of levodopa and also intrapulmonary delivery of apomorphine as well as novel dopaminergic agents like the monoamine oxidase-B inhibitor safinamide or novel catechol-O-methyl transferase inhibitors. An even greater number of ongoing clinical trials assess the efficacy and safety of nondopaminergic approaches to enhance motor control or reduce motor complications like fluctuations and dyskinesias. These include adenosine A2A antagonists, alpha-adrenergic and serotonergic agonists as well as drugs acting on the glutamatergic system. Gene based or cell-based intrastriatal delivery of therapeutic principles that enhance striatal dopaminergic transmission directly or via the stimulation of trophic activity has also reached phase II clinical development with encouraging results in some studies. Finally, a wide spectrum of agents with a potential for slowing disease progression is currently tested. SUMMARY: A variety of medical and nonmedical interventions in different phases of clinical development provide an interesting and promising portfolio of emerging therapies for Parkinson's disease. PMID- 22772875 TI - Biomarkers in Parkinson's disease: an update. AB - PURPOSE OF REVIEW: This review article is focused upon the most recent biomarker studies of Parkinson's disease. It provides an update on promising areas of biomarker research in a rapidly expanding field, and discusses future directions that might lead to successful development of Parkinson's disease biomarkers. RECENT FINDINGS: Studies of molecular-genetic and biochemical biomarkers of Parkinson's disease have not only targeted hypothesis-driven measures of specific substrates involved in processes such as protein misprocessing, but also have made use of sophisticated analyses such as transcriptomic, proteomic, and metabolomic approaches. Whereas none of these are yet established as Parkinson's disease biomarkers, brain imaging using the 123I-ioflupane ligand with single photon emission computed tomography was recently approved in the United States to aid in Parkinson's disease diagnosis, and research on other imaging modalities is ongoing. Neurophysiological tests are also being adapted for biomarker research, and we review recent promising data. SUMMARY: The search for effective biomarkers for diagnosis and surveillance of Parkinson's disease continues. A battery of biomarkers comprising different modalities might be required to address clinical needs in this complex disorder. Critically, collaborative efforts including centralized tissue repository and clinical research infrastructure that are being organized will advance this field further. PMID- 22772876 TI - Genetics of Parkinson disease and other movement disorders. AB - PURPOSE OF REVIEW: We will review the recent advances in the genetics of Parkinson disease and other movement disorders such as dystonia, essential tremor and restless legs syndrome (RLS). RECENT FINDINGS: Mutations in VPS35 were identified as a novel cause of autosomal dominant Parkinson disease using exome sequencing. Next generation sequencing (NGS) was also used to identify PRRT2 mutations as a cause of paroxysmal kinesigenic dyskinesia (DYT10). Using a different technique, that is linkage analysis, mutations in EIF4G1 were implicated as a cause of Parkinson disease and mutations in SLC20A2 as a cause of familial idiopathic basal ganglia calcification. Furthermore, genome-wide association studies (GWAS) and meta-analyses have confirmed known risk genes and identified new risk loci in Parkinson disease, RLS and essential tremor. New models to study genetic forms of Parkinson disease, such as stem cell-derived neurons, have helped to elucidate disease-relevant molecular pathways, such as the molecular link between Gaucher disease and Parkinson disease. SUMMARY: New genes have been implicated in Parkinson disease and other movement disorders through the use of NGS. The identification of risk variants has been facilitated by GWAS and meta-analyses. Furthermore, new models are being developed to study the molecular mechanisms involved in the pathogenesis of these diseases. PMID- 22772877 TI - An update on tremors. AB - PURPOSE OF REVIEW: This review describes the most recent advances in epidemiology, classification, genetics, pathology and treatment of essential tremor. In addition, recent advances in more rare forms of tremor are summarized. RECENT FINDINGS: Clinical, biochemical, pathological and imaging studies suggest an abnormal functioning of the cerebellum in essential tremor. Minor changes of cognition and personality may be due to secondary effects. Dementia and possible shortened life span seem to be limited to late-onset essential tremor. Many of these issues are not yet finally settled and need confirmation in further studies. The current essential tremor classification seems not to reflect the variety of phenotypic expressions. Regarding treatment, there is now a level B evidence for topiramate. Levetiracetam may induce a positive response in Holmes tremor, but is ineffective in orthostatic tremor. SUMMARY: These findings have extended our knowledge about essential tremor. It appears that a new, more distinct classification system is required. Recent treatments have remained unchanged. PMID- 22772878 TI - Huntington's disease. AB - PURPOSE OF REVIEW: This review highlights the recent advances in Huntington's disease, with particular focus on clinical characterization of prodromal Huntington's disease, as well as the growing literature regarding pathophysiological mechanisms and their relevance to potential therapeutic targets. RECENT FINDINGS: Clinical and neuroradiological abnormalities can be demonstrated in gene-positive individuals prior to the onset of manifest Huntington's disease, even as far as 15 years before the disease onset. Although some measures show promise as potential markers of disease progression, further longitudinal studies are required. Several molecular pathways have been implicated in the process of neurodegeneration involved in Huntington's disease and provide potential therapeutic targets. SUMMARY: With predictive testing allowing the identification of gene-positive individuals prior to disease onset, the prodromal stage of Huntington's disease provides an ideal period for the use of disease-modifying therapy. A quantifiable and reliable biomarker for monitoring disease progression is crucial for clinical studies of neuroprotection, and this remains an area of active research. Understanding of the underlying pathophysiological mechanisms continues to grow, based mainly on cellular and animal models of Huntington's disease. PMID- 22772879 TI - Auditory-olfactory synesthesia coexisting with auditory-visual synesthesia. AB - Synesthesia is an unusual condition in which stimulation of one sensory modality causes an experience in another sensory modality or when a sensation in one sensory modality causes another sensation within the same modality. We describe a previously unreported association of auditory-olfactory synesthesia coexisting with auditory-visual synesthesia. Given that many types of synesthesias involve vision, it is important that the clinician provide these patients with the necessary information and support that is available. PMID- 22772881 TI - Antibiotic and heavy metal resistance in bacteria isolated from the Eastern Mediterranean Sea coast. AB - In this study it aimed to determine the microbial diversity, level of antibiotic resistance patterns and distribution of heavy metal resistance of bacterial isolates from the Eastern Mediterranean Sea coast. The resistance of 255 gram negative bacterial isolates to 16 different antibiotics and to 5 heavy metals was investigated. The most common strains isolated from all samples were Citrobacter koseri (9.0%), Escherichia coli (8.2%) and Pantoea agglomerans (8.2%). Our results revealed a high incidence of resistance to ampicillin (74.0%), streptomycin (70.0%) and cefazolin (48.3%). The multiple antibiotic resistance (MAR) index ranged from 0.2 to 0.75. Isolates showed tolerances to different concentrations of heavy metals. Our results show that the Eastern Mediterranean Sea coast has a significant proportion of antibiotic and heavy metal resistant pathogens, or opportunist gram-negative bacteria, and these bacteria may result in a potential public health hazard. PMID- 22772880 TI - Revised recommendations for the management of Gaucher disease in children. AB - Gaucher disease is an inherited pan-ethnic disorder that commonly begins in childhood and is caused by deficient activity of the lysosomal enzyme glucocerebrosidase. Two major phenotypes are recognized: non-neuropathic (type 1) and neuropathic (types 2 and 3). Symptomatic children are severely affected and manifest growth retardation, delayed puberty, early-onset osteopenia, significant splenomegaly, hepatomegaly, thrombocytopenia, anemia, severe bone pain, acute bone crises, and fractures. Symptomatic children with types 1 or 3 should receive enzyme replacement therapy, which will prevent debilitating and often irreversible disease progression and allow those with non-neuropathic disease to lead normal healthy lives. Children should be monitored every 6 months (physical exam including growth, spleen and liver volume, neurologic exam, hematologic indices) and have one to two yearly skeletal assessments (bone density and imaging, preferably with magnetic resonance, of lumbar vertebrae and lower limbs), with specialized cardiovascular monitoring for some type 3 patients. Response to treatment will determine the frequency of monitoring and optimal dose of enzyme replacement. Treatment of children with type 2 (most severe) neuropathic Gaucher disease is supportive. Pre-symptomatic children, usually with type 1 Gaucher, increasingly are being detected because of affected siblings and screening in high-prevalence communities. In this group, annual examinations (including bone density) are recommended. However, monitoring of asymptomatic children with affected siblings should be guided by the age and severity of manifestations in the first affected sibling. Treatment is necessary only if signs and symptoms develop. CONCLUSION: Early detection and treatment of symptomatic types 1 and 3 Gaucher disease with regular monitoring will optimize outcome. Pre-symptomatic children require regular monitoring. Genetic counseling is important. PMID- 22772883 TI - [Vitamin D metabolism]. AB - In this review article the focus is on vitamin D metabolism, the function of vitamin D, the current state of knowledge of vitamin D in inflammatory rheumatic diseases and vitamin D supplementation including safety and practice-oriented tips. PMID- 22772884 TI - [Physiotherapy and ergotherapy are indispensable. Concrete prescription of remedies - without recourse]. AB - Physical therapy and occupational therapy are essential for the treatment of inflammatory rheumatic diseases equal in rank to any drug therapy. They have enough evidence and are part of all current guidelines even if mostly not specified. In the German social security system the doctor prescribing physical therapy or occupational therapy has to act according to the different rules and forms as described in the current "Heilmittel Richtlinie" (Remedy directive) effective since July 2011. The multiple formal conditions and requirements of prescriptions are described in detail. Of special interest is that the global diagnosis of rheumatoid arthritis can no longer be used as the reason or justification for the individual prescription but detailed sub-diagnoses, regarding the essential ICF domains of structural damage, functional impairment, activity limitation and participation restriction as well as individual context factors are necessary. Of special interest is the fact that the prescribing doctor is no longer responsible for the formal correctness of prescriptions but the performing therapist, who will not be reimbursed if the prescription shows even minor formal errors. Another important improvement is the newly introduced long-term prescription of physical and occupational therapy. This facilitates the application of these therapies in the multimodal treatment regimen of rheumatic diseases. PMID- 22772885 TI - [Molecular physical medicine]. AB - A multimodal treatment of inflammatory rheumatic diseases without physical medicine is almost always incomplete. The mechanisms underlying the positive effects of physical medicine are only partially understood. Modern molecular medicine offers new insights into pivotal mechanisms and mediators of the inflammatory process and into interactions between cells of the immune system and the bone. Investigating the potential influences of different methods of physical medicine on the central regulatory processes of inflammatory rheumatic diseases is of great interest, highly fascinating and opens up new avenues of research for the future. This article focuses on the first novel results of molecular physical medicine in rheumatic and degenerative diseases. PMID- 22772886 TI - [Rheumatic joint disease in childhood and adolescence ]. AB - Rheumatic joint disease in childhood and adolescence is relatively rare. In the general population, 1 child with juvenile arthritis accounts for 100 adult patients with rheumatoid arthritis. At disease onset 50% of affected children are between 2 and 6 years of age. Symptoms are often subtle and pain is usually not the leading symptom. Early treatment of juvenile arthritis is essential in order to prevent long-term sequelae in affected children. Many children are introduced to a pediatric rheumatologist only with considerable delay. Therapy is based on NSAIDs, intra-articular steroid injections, and immunosuppressive drugs. In severe cases patients are treated with biologics. Physical and occupational therapy are important supportive measures in the treatment. PMID- 22772887 TI - [Th9 cells. Functionally important or just an epiphenomenon?]. AB - Development of the recently described Th9 cells is selectively and dynamically controlled by epigenetic modifications. The selective epigenetic inactivation of the PU.1 promoter associated with diminished Th9 cell differentiation by naive CD4 T cells allows the assumption of a special physiologic role of IL-9. Once deregulated, IL-9 seems to play an important role in the pathogenesis of several autoimmune disorders. PMID- 22772888 TI - [Safety of immunosuppressants]. AB - METABOLISM: Cyclosporin A and leflunomide may increase the blood pressure, whereas administration of prednisolone and tacrolimus may cause hyperglycemia. Azathioprine, chloroquine, methotrexate and mycophenolate mofetil seem to be metabolically neutral. Tocilizumab and tumor necrosis factor (TNF) alpha blockers have a negative effect on the lipid profile. INFECTIONS: The overall infection risk for prednisolone is estimated to be 1.3. This risk for methotrexate is also 1.3 compared to other disease modifying antirheumatic drugs (DMARDs). Regarding biologics, the highest risk of serious infections was associated with certolizumab pegol and tocilizumab, in contrast to abatacept and rituximab which showed the lowest risk. CANCER RISK: Azathioprine and cyclosporin A are associated with a markedly increased risk of non-melanoma skin cancer. According to the RABBIT registry no significant increase in tumor rate has been reported for biologics. PREGNANCY: Azathioprine, chloroquine, cyclosporin A, prednisolone, sulfasalazine, tacrolimus and cyclophosphamide (only after the second trimester) may be administered during pregnancy. Biologics should be avoided unless there is a treatment need in cases of uncontrolled disease activity. BREAST FEEDING: Only chloroquine, prednisolone, sulfasalazine and tacrolimus may be taken during breast feeding. There are insufficient data on the safety of biologics. PMID- 22772889 TI - [Magnetic resonance angiography in rheumatology]. AB - The potentials and pitfalls of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) in the diagnosis of large vessel vasculitis are summarized in this review article. With the ability to visualize the lumen and vessel walls of large and medium sized arteries, MRI and MRA have great potential to play a unique role in the diagnosis of large vessel vasculitis. This is underlined by the fact that mural inflammatory changes typically involve uptake of contrast agent that can be visualized with MRI. The cranial, intracranial and extracranial involvement pattern can be studied in a combined approach including an MRI examination of the superficial cranial arteries and an MRA examination of the thoracic aorta with its major supra-aortic branches. Typical MRI sequence parameters are given including monophasic MRA and time-resolved MRA protocols at 3 T. The MRI and MRA techniques have the potential to determine the most suitable (inflamed) segment for temporal artery biopsy and to monitor treatment. Initial results of multicenter studies for the diagnostic accuracy of these relatively new methods are expected soon. The MRA technique is recognized as an interesting alternative to invasive catheter angiography for the evaluation of central nervous system (CNS) vasculitis. PMID- 22772893 TI - Undertreatment of pain in older adults: an application of beneficence. AB - Inadequate pain control, especially in older adults, remains a significant issue when caring for this population. Older adults, many of whom experience multiple acute and chronic conditions, are especially vulnerable to having their pain seriously underassessed and inadequately treated. Nurses have an ethical obligation to appropriately treat patients' pain. To fulfill their ethical obligation to relieve pain in older patients, nurses often need to advocate on their behalf. This article provides an overview of the persistent problem of undertreated pain in older adults and explores how nurses can meet this ethical duty through the application of Beauchamp and Childress' three principles of beneficence. PMID- 22772894 TI - Elinogrel, an orally and intravenously available ADP-receptor antagonist. How does elinogrel affect a personalized antiplatelet therapy? AB - The antiplatelet therapy with aspirin and the ADP-receptor blocker clopidogrel is currently the standard medication after coronary intervention or after acute coronary syndrome to prevent recurrent ischemic events and reduce mortality. However, high interindividual response variability to antiplatelet treatment is described in up to 44% of treated patients. A poor response to clopidogrel is caused by multifactorial mechanisms. Individual risk assessment including platelet function testing (PFT) can help to identify high risk patients, although recent randomized trials to investigate effects of PFT-guided therapy have failed to detect an impact on prognostic outcome. Poor response to standard antiplatelet agents can be overcome by switching to alternate substances. Elinogrel is a novel competitive, reversible ADP-receptor antagonist available in oral and intravenous formulation. Additional treatment with elinogrel showed advantages over clopidogrel, including more rapid, less variable, and more complete inhibition of platelet function without significantly increased bleeding complications. This review gives an overview over the investigational drug elinogrel for use in a personalized antiplatelet approach. PMID- 22772895 TI - Genome DNA Sequence Variation, Evolution, and Function in Bacteria and Archaea. AB - Comparative genomics has revealed that variations in bacterial and archaeal genome DNA sequences cannot be explained by only neutral mutations. Virus resistance and plasmid distribution systems have resulted in changes in bacterial and archaeal genome sequences during evolution. The restriction-modification system, a virus resistance system, leads to avoidance of palindromic DNA sequences in genomes. Clustered, regularly interspaced, short palindromic repeats (CRISPRs) found in genomes represent yet another virus resistance system. Comparative genomics has shown that bacteria and archaea have failed to gain any DNA with GC content higher than the GC content of their chromosomes. Thus, horizontally transferred DNA regions have lower GC content than the host chromosomal DNA does. Some nucleoid-associated proteins bind DNA regions with low GC content and inhibit the expression of genes contained in those regions. This form of gene repression is another type of virus resistance system. On the other hand, bacteria and archaea have used plasmids to gain additional genes. Virus resistance systems influence plasmid distribution. Interestingly, the restriction modification system and nucleoid-associated protein genes have been distributed via plasmids. Thus, GC content and genomic signatures do not reflect bacterial and archaeal evolutionary relationships. PMID- 22772896 TI - Repolarization changes underlying long-term cardiac memory due to right ventricular pacing: noninvasive mapping with electrocardiographic imaging. AB - BACKGROUND: Cardiac memory refers to the observation that altered cardiac electrical activation results in repolarization changes that persist after the restoration of a normal activation pattern. Animal studies, however, have yielded disparate conclusions, both regarding the spatial pattern of repolarization changes in cardiac memory and the underlying mechanisms. The present study was undertaken to produce 3-dimensional images of the repolarization changes underlying long-term cardiac memory in humans. METHODS AND RESULTS: Nine adult subjects with structurally normal hearts and dual-chamber pacemakers were enrolled in the study. Noninvasive electrocardiographic imaging was used before and after 1 month of ventricular pacing to reconstruct epicardial activation and repolarization patterns. Eight subjects exhibited cardiac memory in response to ventricular pacing. In all subjects, ventricular pacing resulted in a prolongation of the activation recovery interval (a surrogate for action potential duration) in the region close to the site of pacemaker-induced activation from 228.4+/-7.6 ms during sinus rhythm to 328.3+/-6.2 ms during cardiac memory. As a consequence, increases are observed in both apical-basal and right-left ventricular gradients of repolarization, resulting in a significant increase in the dispersion of repolarization. CONCLUSIONS: These results demonstrate that electrical remodeling in response to ventricular pacing in human subjects results in action potential prolongation near the site of abnormal activation and a marked dispersion of repolarization. This dispersion of repolarization is potentially arrhythmogenic and, intriguingly, was less evident during continuous right ventricular pacing, suggesting the novel possibility that continuous right ventricular pacing at least partially suppresses pacemaker induced cardiac memory. PMID- 22772897 TI - Does location of epicardial adipose tissue correspond to endocardial high dominant frequency or complex fractionated atrial electrogram sites during atrial fibrillation? AB - BACKGROUND: Although increased epicardial adipose tissue (EAT) volume is known to be associated with increased prevalence of atrial fibrillation (AF), the exact mechanisms are unclear. Therefore, we investigated whether EAT locations were associated with high dominant frequency (DF) sites or complicated fractionated atrial electrogram sites during AF. METHODS AND RESULTS: Three-dimensional reconstruction computed tomography images depicting EAT volumes (obtained by 320 detector-row multislice computed tomography) were merged with NavX-based DF and complicated fractionated atrial electrogram maps obtained during AF for 16 patients with paroxysmal AF and for 18 patients with persistent AF. Agreement between locations of the EAT, especially EAT surrounding the left atrium, and of high DF or complicated fractionated atrial electrogram sites was quantified. In addition, serum biomarker levels were determined. EAT surrounding the left atrium volumes was significantly greater in patients with persistent AF than in patients with paroxysmal AF (52.9 cm(3) [95% CI, 44.2-61.5] versus 34.8 cm(3) [95% CI, 26.6-43.0]; P=0.007). Serum high-sensitivity C-reactive protein and interleukin-6 levels were significantly higher in persistent AF patients than in paroxysmal AF patients (median high-sensitivity C-reactive protein, 969 ng/mL [interquartile range, 307-1678] versus 320 ng/mL [interquartile range, 120-660]; P=0.008; median interleukin-6, 2.4 pg/mL [interquartile range, 1.7-3.2] versus 1.3 [interquartile range, 0.8-2.4] pg/mL; P=0.017). EAT locations were in excellent agreement with high DF sites (kappa=0.77 [95% CI, 0.71-0.82]) but in poor agreement with complicated fractionated atrial electrogram sites (kappa=0.22 [95% CI, 0.13 0.31]). CONCLUSIONS: Increased EAT volume and elevation of inflammatory biomarkers are noted in persistent AF rather than paroxysmal AF patients. High DF sites are located adjacent to EAT sites. Thus, EAT may be involved in the maintenance of AF. PMID- 22772898 TI - Trans-fatty acid consumption and heart rate variability in 2 separate cohorts of older and younger adults. AB - BACKGROUND: Trans-fatty acid (TFA) consumption is associated with risk of coronary heart disease, and trans-18:2, but not trans-18:1, in red blood cell membranes has been associated with sudden cardiac arrest. Abnormal heart rate variability (HRV) reflects autonomic dysfunction and predicts cardiac death. Relationships between TFA consumption and HRV remain understudied. We determined whether total TFA consumption, as well as trans-18:1 and trans-18:2 TFA consumption, was independently associated with HRV in 2 independent cohorts in the United States and Portugal. METHODS AND RESULTS: In 2 independent cohorts of older US adults (Cardiovascular Health Study [CHS], age 72+/-5 years, 1989/1995) and young Portuguese adults (Porto, age 19+/-2 years, 2008/2010), we assessed habitual TFA intake by food frequency questionnaires in CHS (separately estimating trans-18:1 and trans-18:2) and multiple 24-hour recalls in Porto (estimating total TFA only, which in a subset correlated with circulating trans 18:2 but not trans-18:1, suggesting that we captured the former). HRV was assessed using 24-hour Holters in CHS (n=1076) and repeated short-term (5-minute) ECGs in Porto (n=160). We used multivariate-adjusted linear regression to relate TFA consumption to HRV cross-sectionally (CHS, Porto) and longitudinally (CHS). In CHS, higher trans-18:2 consumption was associated with lower 24-hour SD of all normal-to-normal intervals both cross-sectionally (-12%; 95% CI, -19% to -6%; P=0.001) and longitudinally (-15%; 95% CI, -25% to -4%; P= 0.009) and lower 24 hour SD of 5-minute average N-N intervals and mean of the 5-minute SD of N-N intervals calculated over 24 hours (P<0.05 each). Higher trans-18:1 consumption in CHS was associated with more favorable 24-hour HRV in particular time-domain indices (24-hour SD of all normal-to-normal intervals, SD of 5-minute average N-N intervals, mean of the 5-minute SD of N-N intervals calculated over 24 hours; P<0.05 each). In Porto, each higher SD TFA consumption was associated with 4% lower 5-minute 24-hour SD of all normal-to-normal intervals (95% CI, -8% to -1%; P=0.04) and 7% lower 5-minute square root of the mean of the squares of successive N-N differences (95% CI, -13% to -1%; P=0.04). CONCLUSIONS: Trans-18:2 consumption is associated with specific, less favorable indices of HRV in both older and young adults. Trans-18:1 consumption is associated with more favorable HRV indices in older adults. Our results support the need to investigate potential HRV-related mechanisms, whereby trans-18:2 may increase arrhythmic risk. PMID- 22772899 TI - Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume. AB - Synaptic plasticity in many regions of the central nervous system leads to the continuous adjustment of synaptic strength, which is essential for learning and memory. In this study, we show by visualizing synaptic vesicle release in mouse hippocampal synaptosomes that presynaptic mitochondria and, specifically, their capacities for ATP production are essential determinants of synaptic vesicle exocytosis and its magnitude. Total internal reflection microscopy of FM1-43 loaded hippocampal synaptosomes showed that inhibition of mitochondrial oxidative phosphorylation reduces evoked synaptic release. This reduction was accompanied by a substantial drop in synaptosomal ATP levels. However, cytosolic calcium influx was not affected. Structural characterization of stimulated hippocampal synaptosomes revealed that higher total presynaptic mitochondrial volumes were consistently associated with higher levels of exocytosis. Thus, synaptic vesicle release is linked to the presynaptic ability to regenerate ATP, which itself is a utility of mitochondrial density and activity. PMID- 22772900 TI - Effect of semax and its C-terminal fragment Pro-Gly-Pro on the expression of VEGF family genes and their receptors in experimental focal ischemia of the rat brain. AB - The synthetic peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is used successfully in acute stroke therapy. In spite of numerous studies on the subject, many aspects of the neuroprotective effects of the peptide remain unknown. We studied the action of Semax and its C-terminal tripeptide Pro-Gly-Pro on the expression of the VEGF gene family (Vegf-a, Vegf-b, Vegf-c, Vegf-d, and Plgf) and their receptors (Vegfr-1, Vegfr-2, and Vegfr-3) in the frontoparietal cortex region of the rat brain at 3, 24, and 72 h after permanent left middle cerebral artery occlusion (pMCAO). The relative mRNA level of the genes studied was assessed using real-time reverse transcription-PCR. The Vegf-b and Vegf-d genes were most affected by the peptides, which resulted in their most noticeable activation at 3 h after pMCAO. The level of Vegf-d transcripts decreased considerably, whereas the mRNA level of the Vegf-b gene was significantly increased after 72 h of treatment with each of the peptides. In addition, the effects of the peptides on the expression of the Vegf-b and Vegf-d genes were the opposite of the action of ischemia. It is suggested that the identified effects of the peptides diminish the effects of ischemia, thus participating in the positive therapeutic effect of Semax on ischemic stroke. PMID- 22772901 TI - Protective effect of carbamazepine on kainic acid-induced neuronal cell death through activation of signal transducer and activator of transcription-3. AB - Studies have shown that the protective effect of carbamazepine (CBZ) on seizure induced neuronal injury. However, its precise mechanisms remain unknown. Here, to investigate the neuroprotective mechanism of CBZ against seizure-induced neuronal cell death, we identified the change of gene expressions by CBZ in the hippocampus of kainic acid (KA)-treated mice using microarray method, and studied the involvement of candidate gene in neuroprotective action of CBZ. KA (15 mg/kg) and/or CBZ (30 mg/kg, 0.5 h after KA exposure) were injected intraperitoneally into mice. Through microarray analysis, we found that signal transducer and activator of transcription-3 (Stat3) gene expression was upregulated in the hippocampal CA3 region, 24 h after KA injection (15 mg/kg), and that CBZ further elevated Stat3 expression in KA-treated mice. KA also increased the protein level and phosphorylation of Stat3, and CBZ further increased the Stat3 phosphorylation, without changing Stat3 protein level in KA-treated mice. In particular, phospho-Stat3 immunoreactivity (IR) by KA was shown in astrocytes rather than in neurons; whereas phospho-Stat3 IR by CBZ in KA-treated mice was observed predominantly in neurons, and also in neuroprotective protein Bcl-xL expression cells. These results indicate that Stat3 may play an important role in neuroprotective action of CBZ on seizure-induced neuronal injury. PMID- 22772902 TI - Phage biology: Phages find a backbone. PMID- 22772903 TI - Microbial colonization and controls in dryland systems. AB - Drylands constitute the most extensive terrestrial biome, covering more than one third of the Earth's continental surface. In these environments, stress limits animal and plant life, so life forms that can survive desiccation and then resume growth following subsequent wetting assume the foremost role in ecosystem processes. In this Review, we describe how these organisms assemble in unique soil- and rock-surface communities to form a thin veneer of mostly microbial biomass across hot and cold deserts. These communities mediate inputs and outputs of gases, nutrients and water from desert surfaces, as well as regulating weathering, soil stability, and hydrological and nutrient cycles. The magnitude of regional and global desert-related environmental impacts is affected by these surface communities; here, we also discuss the challenges for incorporating the consideration of these communities and their effects into the management of dryland resources. PMID- 22772904 TI - Thermal energy dissipation and xanthophyll cycles beyond the Arabidopsis model. AB - Thermal dissipation of excitation energy is a fundamental photoprotection mechanism in plants. Thermal energy dissipation is frequently estimated using the quenching of the chlorophyll fluorescence signal, termed non-photochemical quenching. Over the last two decades, great progress has been made in the understanding of the mechanism of thermal energy dissipation through the use of a few model plants, mainly Arabidopsis. Nonetheless, an emerging number of studies suggest that this model represents only one strategy among several different solutions for the environmental adjustment of thermal energy dissipation that have evolved among photosynthetic organisms in the course of evolution. In this review, a detailed analysis of three examples highlights the need to use models other than Arabidopsis: first, overwintering evergreens that develop a sustained form of thermal energy dissipation; second, desiccation tolerant plants that induce rapid thermal energy dissipation; and third, understorey plants in which a complementary lutein epoxide cycle modulates thermal energy dissipation. The three examples have in common a shift from a photosynthetically efficient state to a dissipative conformation, a strategy widely distributed among stress tolerant evergreen perennials. Likewise, they show a distinct operation of the xanthophyll cycle. Expanding the list of model species beyond Arabidopsis will enhance our knowledge of these mechanisms and increase the synergy of the current studies now dispersed over a wide number of species. PMID- 22772909 TI - Chemically modified graphene oxides as a hole transport layer in organic solar cells. AB - We demonstrate O(2) plasma treated graphene oxides with a work function of 5.2 eV as a high performance hole transport layer in organic solar cells. The high transparency and high work function simultaneously increase short circuit current, threshold voltage and fill factor, resulting in a 30% increase in cell efficiency. PMID- 22772910 TI - New findings validate an ancient technique: how massage affects the biochemistry of inflammation. PMID- 22772908 TI - Genes for plant autophagy: functions and interactions. AB - Autophagy, or self-consuming of cytoplasmic constituents in a lytic compartment, plays a crucial role in nutrient recycling, development, cell homeostasis, and defense against pathogens and toxic products. Autophagy in plant cells uses a conserved machinery of core Autophagy-related (Atg) proteins. Recently, research on plant autophagy has been expanding and other components interacting with the core Atg proteins are being revealed. In addition, growing evidence suggests that autophagy communicates with other cellular pathways such as the ubiquitin proteasome system, protein secretory pathway, and endocytic pathway. An increase in our understanding of plant autophagy will undoubtedly help test the hypothesized functions of plant autophagy in programmed cell death, vacuole biogenesis, and responses to biotic, abiotic, and nutritional stresses. In this review, we summarize recent progress on these topics and suggest topics for future research, after inspecting common phenotypes of current Arabidopsis atg mutants. PMID- 22772911 TI - Protective effect of an extract of Guipi Pill against radiation-induced damage in mice. AB - OBJECTIVE: To study the protective effect of an extract of Guipi Pill () against radiation-induced damage. METHODS: A total of 100 Kunming mice were randomly divided into normal group, model group, positive drug group (treated with radioprotective agent "523", 5 mg/kg at 24 h before irradiation) and two treatment groups, with 20 mice in each group. The extract of water extraction alcohol precipitation (WAP) from Guipi Pill were administered orally to the mice in the two treatment groups at the dose of 500 and 1,000 mg/kg, respectively, for 6 days prior to whole body radiation (8 Gy). Fifty mice with 10 in each group were used to observe the survival rate 30 days after radiation. The other 50 mice with 10 in each group were sacrificed on day 10 after radiation (6 Gy) in order to take blood, liver and unilateral femur. RESULTS: Pretreatment prior to irradiation with WAP resulted in a significantly higher 30-day survival rate of mice after exposure to a potentially lethal dose of 8-Gy radiation. WAP could significantly increase the total white blood cell count and DNA content of bone marrow, and it also increased the activity of various antioxidant enzymes, such as superoxide dismutase, catalase, total antioxidant capacity and glutathione peroxidase in liver tissue of mice, which were reduced by radiation treatment. Maleic dialdehyde level and bone marrow micronucleus rate were significantly reduced by WAP, which were increased after 6-Gy radiation. CONCLUSION: WAP of Guipi Pill could increase the 30-day survival rate and the antioxidant capacity as well as protect bone marrow in mice. WAP of Guipi Pill is an effective radioprotective agent. PMID- 22772912 TI - A microarray analysis of angiogenesis modulation effect of Xuefu Zhuyu Decoction on endothelial cells. AB - OBJECTIVE: To study the angiogenesis modulation mechanism of Xuefu Zhuyu Decoction () on the endothelial cell line ECV304. METHODS: ECV304 cells were treated with 2.5% Xuefu Zhuyu Decoction-containing serum (XFZYD-CS) for 24 h, 48 h or 72 h. Thiazolyl blue tetrazolium bromide (MTT), fluorescence activating cell sorter (FACS), migration, adhesion and in vitro tube formation assays were conducted to confirm an angiogenesis effect of XFZYD at 3 time points. An analysis of angiogenesis regulator profiles was performed at 3 times with real time polymerase chain reaction (RT-PCR) superarray. RESULTS: At 48 h, XFZYD-CS induced ECV304 significantly improved cell viability, number in S phase, migration, adhesion and tube formation. At 24 h and 72 h, only cell migration was elevated. Microarray results showed that the expression of 27 angiogenesis related genes was changed. CONCLUSION: XFZYD-CS treatment induced angiogenesis on ECV304 cells with significant cellcular changes occurring at 48 h and genetic changes as early as 24 h. PMID- 22772913 TI - Effect of Yifei Huoxue Granule on the proliferation of rat pulmonary artery smooth muscle cells upon exposure to chronic hypoxic conditions in vitro. AB - OBJECTIVE: To investigate the inhibitory effect of Yifei Huoxue Granule (, YFHXG) on the hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and its mechanism of decreasing pulmonary arterial pressure. METHODS: Twenty male Sprague-Dawley (SD) rats were randomly divided into four groups: saline, and 0.66, 3.30 and 16.50 g/kg of YFHXG groups, the saline and different concentrations of YFHXG were given twice daily for 7 days, respectively. Serum pharmacology method was used in the preparation of YFHXG serum. Tissue block anchorage was employed in the primary culture of rat PASMCs. The PASMCs were randomly divided into normoxia group, hypoxia group, and hypoxia+YFHXG group (0.66, 3.30 and 16.50 g/kg doses of YFHXG-treated serum groups, exposed to hypoxic condition). PASMCs in normoxia and hypoxia group were cultured with saline serum, hypoxia+YFHXG groups were cultured with different concentrations of YFHXG serum. Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Cell cycle was analyzed using flow cytometry. In addition, hypoxia inducible factor-1-alpha (HIF-1alpha) protein expression was evaluated by immunocytochemistry analysis, the concentration of intracellular reactive oxygen species (ROS) and Ca(2+) were determined by laser scanning confocal microscopy (LSCM). RESULTS: MTT assay and flow cytometry showed that hypoxia could directly activate the proliferation of PASMCs, while YFHXG dose-dependently inhibited hypoxia-induced proliferation of rat PASMCs. Immunocytochemistry showed that hypoxia enhanced HIF-1alpha protein expression, and LSCM showed that hypoxia significantly increased intracellular ROS and Ca(2+), while YFHXG decreased the expression of HIF- 1alpha and attenuated the hypoxia-induced increase in intracellular concentration of ROS and Ca(2+). CONCLUSIONS: YFHXG could inhibit hypoxia-induced proliferation of rat PASMCs, which may decrease pulmonary arterial pressure and vascular remodeling. The anti hypoxia effect of YFHXG may be explained by its regulation of HIF-1alpha expression and of the levels of intracellular ROS and Ca(2+). PMID- 22772914 TI - Role of beta2-adrenoceptor-beta-arrestin2-nuclear factor-kappaB signal transduction pathway and intervention effects of oxymatrine in ulcerative colitis. AB - OBJECTIVE: To investigate the beta2-adrenoceptor (beta2AR)-beta-arrestin2-nuclear factor-kappaB (NF-kappaB) signal transduction pathway and the intervention effects of oxymatrine in a rat model of ulcerative colitis. METHODS: Forty SD rats were randomly divided into four groups, which included the normal control group, the model group, the mesalazine group and the oxymatrine treatment group, with 10 rats per group. Experimental colitis induced with trinitrobenzene sulfonic acid (TNBS) was established in each group except the normal control group. The rats in the oxymatrine treatment group were treated with intramuscular injection of oxymatrine 63 mg/(kg.d) for 15 days and the rats in the mesalazine group were treated with mesalazine solution 0.5 g/(kg.d) by gastric lavage for 15 days. The rats in the normal control group and model group were treated with 3 mL water by gastric lavage for 15 days. Diarrhea and bloody stool were carefully observed. Histological changes in colonic tissue were examined on day 7 in 2 rats per group that were randomly selected. The expression of beta2AR, beta-arrestin2 and NF-kappaB p65 in colon tissue and spleen lymphocytes were detected with immunohistochemistry and Western immunoblotting techniques on day 16 after fasting for 24 h. Six rats died of lavage with 2 each in the normal control, the model group and the mesalazine group; and were not included in the analysis. RESULTS: The rats in the model group suffered from looser stool and bloody purulent stool after modeling. But in the oxymatrine and mesalazine groups, looser stool and bloody purulent stool reduced after treatment. And the colonic wall in the model group was thickened and the colon length shortened. The colon mucosa was congested in multiple areas with edema, erosion, superficial or linear ulcer and scar formation, while the intestinal mucosa injury reduced in the mesalazine and oxymatrine groups (P<0.01). In colonic mucosa and in spleen lymphocytes, compared with the normal control group, the expression of NF kappaBp65 were significantly increased (P<0.01) in the model group while the expressions of beta 2AR and beta-arrestin2 were significantly decreased (P<0.01). Compared with the model group, the expression of NF-kappa Bp65 was significantly decreased in the mesalazine group (P<0.01) and oxymatrine treatment group (P<0.01) while the expressions of beta2AR and beta-arrestin2 were significantly increased (P<0.01). There were no statistically significant differences in the expression of beta2AR, beta-arrestin2 and NF-kappaBp65 between the mesalazine group and oxymatrine group (P>0.05). CONCLUSIONS: The beta2AR-beta-arrestin2-NF kappaB signal transduction pathway participated in the pathologic course of ulcerative colitis. Oxymatrine attenuated ulcerative colitis through regulating the beta2AR-beta-arrestin2-NF-kappaB signal transduction pathway. PMID- 22772915 TI - Tounongsan extract induces apoptosis in cultured Raji cells. AB - OBJECTIVE: To investigate the effects of Tounongsan () extract (TNSE) on proliferation and apoptosis of the human lymphoma cell line Raji and its possible mechanism of action. METHODS: The viability of TNSE-treated Raji cells was measured by a 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was determined by flow cytometry. The molecular mechanisms of TNSE-mediated apoptosis were further investigated by reverse transcription polymerase chain reaction (RT-PCR) analysis of the mRNA expression of nuclear factor kappaB (NF-kappaB), Bcl-xL, Bcl-2-associated death promoter (Bad), caspase 9 and caspase-3. Western blotting was used to detect the protein expressions of NF-kappaB, Bad, cleaved caspase-9 and cleaved caspase-3. RESULTS: TNSE inhibited Raji cell proliferation in dose- and time-dependent manners. After 48-h treatment with various concentrations of TNSE (125, 250 and 500 MUg/mL), the apoptosis rates of Raji cell were 12.23%+/-1.98% (P<0.05), 20.97%+/-3.96% (P<0.01) and 30.4%+/-4.87% (P<0.01), respectively, compared with those of the control (6.02%+/ 1.01%). RT-PCR demonstrated that NF-kappaB mRNA expression was significantly downregulated in Raji cells treated with 250 MUg/mL TNSE for 48 h (P<0.05), while Bad, caspase-9 and caspase-3 mRNA levels were upregulated (P<0.05). Moreover, TNSE treatment resulted in downregulation of NF-kappaB protein expression and strikingly upregulated protein expressions of Bad, cleaved caspase-9, cleaved caspase-3 in a dose-dependent manner, as determined by Western blot. CONCLUSION: TNSE exhibits significant anti-proliferative and apoptotic effects in Raji cells, which may be involved in regulation of NF-kappaB and Bad, and activation of caspase-9 and caspase-3. PMID- 22772916 TI - Mitochondrial proteomic analysis of isopsoralen protection against oxidative damage in human lens epithelial cells. AB - OBJECTIVE: To investigate the protective effects of the natural medicinal monomer isopsoralen (ISR) with estrogenic activity against oxidative damage in human lens epithelial cells B3 (HLE-B3) caused by hydrogen peroxide (H(2)O(2)) and to pursue the possible mitochondrial proteomic regularity of the protective effects. METHODS: HLE-B3 cells were treated with H(2)O(2) (300 MU mol/L), beta-estradiol (E(2): 10(-8) mol/L) and H(2)O(2), ISR (10(-5) mol/L) and H(2)O(2), or left untreated. Altered expressions of all mitochondrial proteins were analyzed by protein array and surfaceenhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS). The mass/charge (m/z) ratios of each peak were tested by the Kruskal-Wallis rank sum test, and the protein peak value of the m/z ratio for each treatment by pair comparison was analyzed with the Nemenyi test. RESULTS: H(2)O(2) up-regulated the expressions of two protein spots (with m/z of 6532 and 6809). E(2) mitigated the oxidative damage, and the expression of one protein spot (m/z 6532) was down-regulated. In contrast, ISR down-regulated both of protein spots (m/z 6532 and 6809). CONCLUSIONS: ISR could effectively inhibit H(2)O(2)-induced oxidative damage in HLE-B3 cells. The protein spot at m/z of 6532 might be the target spot of ISR against oxidative damage induced by H(2)O(2). PMID- 22772917 TI - Profiles of traditional Chinese medicine schools. AB - Many schools of academic doctrines have emerged throughout the development history of traditional Chinese medicine (TCM) due to geographic, time, Shicheng (mentor-apprentice system) and academic diversities. Classic TCM School, Classic Formula School and Febrile Disorder School, though all lacking a clearly demonstrable or continuous Shicheng relationship, are nevertheless so classified because of their consistency in reference to the classic TCM works. Each of the Four Famous Masters of Jin and Yuan Dynasties had its distinctively different academic doctrine, resulting in the establishment of individually integrated academic schools. The emergence of the Warming and Tonifying School in late Yuan and early Ming Dynasties was realized as a means to rectify the ill effects of the cool and cold medications prevalent at the time. On the other hand, the advent of the Warm Disease School and the rise of the Confluence School embodied the close relationship carried by TCM academic schools to contemporary historical background. Looking at this development history, it is evident that the development of TCM academic schools could flourish only if it allows dissenting, yet mutually tolerant, opinions. In present medical environment where TCM and Western medicine are of equal importance, Classic TCM Schools, TCM Modernization Schools and Integrative Medicine Schools should all receive emphasis to foster development. PMID- 22772918 TI - Isobavachalcone: an overview. AB - Isobavachalcone (IBC) or (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)-phenyl]-3-(4 hydroxyphenyl)-2-propen-1-one or (E)-4,2',4'-trihydroxy-3'-prenylchalcone; 2',4,4'-trihydroxy-3'-prenyl-transchalcone, is a prenylated chalcone of the class flavonoid, firstly isolated from Psoralea corylifolia in 1968. IBC is known to possess a wide spectrum of biological activities, antibacterial, antifungal, anticancer, anti-reverse transcriptase, antitubercular and antioxidant. The compound was isolated from plant families, mostly Moraceae and Fabaceae. This review brings out together the knowledge on IBC, and can serve as the start point for future research and valorization accomplishments. PMID- 22772920 TI - Summary of 2011 Integrative Medical Doctors Conference. PMID- 22772919 TI - Roles and mechanisms of ginseng in protecting heart. AB - Ginseng, the root of Panax ginseng C. A. Mayer, has long been used clinically in China to treat various diseases. Multiple effects of ginseng, such as antitumor, antiinflammatory, antiallergic, antioxidative, antidiabetic and antihypertensive have been confirmed by modern medicine. Recently, the clinical utilization of ginseng to treat heart diseases has increased dramatically. The roles of ginseng in protecting heart are foci for research in modern medical science and have been partially demonstrated, and the mechanisms of protection against coronary artery disease, cardiac hypertrophy, heart failure, cardiac energy metabolism, cardiac contractility, and arrhythmia are being uncovered progressively. However, more studies are needed to elucidate the complex mechanisms by which ginseng protects heart. All such studies will provide evidence of ginseng's clinical application, international promotion, and new drug development. PMID- 22772921 TI - The impact of curcumin on breast cancer. AB - Curcumin, the active ingredient of turmeric (curry spice), is believed to be associated with reducing the incidence of breast cancers in Asian countries. Anti cancer efficacy of curcumin and analogs has been tested in pre-clinical studies in some cancer models including breast cancer. These studies reported promising results in inhibiting human cancer cell proliferation and tumorigenesis in animal models. Both in vitro and in vivo studies have shown that curcumin and its analogs target critical genes associated with angiogenesis, apoptosis, cell cycle, and metastasis. The inhibition of human breast cancer cell growth by curcumin is mediated via certain signaling cascades including the modulation of the NF-kappaB signaling pathway. Epidemiological and experimental data also demonstrated the efficacy of curcumin in chemoprevention and reversing chemo resistance of tumors of certain cancers. This review summarizes the studies revealing the preventive and therapeutic effects of curcumin and its analogs with an emphasis on multi-targeted biological and molecular effects in a breast cancer model. PMID- 22772922 TI - Epilepsy and driving. PMID- 22772923 TI - Systemic review of aripiprazole for the treatment of children and adolescents with tic disorders. AB - This study aimed to systematically review the data related to the treatment of tic disorders through aripiprazole administration, an atypical antipsychotic. The databases of MEDLINE/PubMed and Google Scholar were searched using the key words: "aripiprazole," "tic," and "Tourette," and the relevant titles retrieved. Thirty five articles met the inclusion criteria and were further scrutinized. Most of the articles were case reports, and only 2 published trials included control groups. The number of randomized double-blind controlled clinical trials was zero, therefore, no strong evidence, provided by one, or more well-designed randomized controlled clinical trials, was found. Current evidence suggests that aripiprazole is effective for treating tic and Tourette disorders in both children and adolescents. Moreover, it seems that its adverse effect profile is safer than pimozide and some other antipsychotics. Therefore, double-blind randomized placebo-controlled studies are needed to provide strong evidence on the issue. PMID- 22772924 TI - Delirium. A comprehensive review. AB - Delirium is among the most common potentially preventable neurological disorders encountered in diverse patient populations, especially in critical care units and the elderly. It may present with highly variable clinical features, prolong hospital stay, and herald a poor prognosis. It is also a source of distress for patients and their caregivers. A high degree of clinical suspicion is required for detecting delirium and a detailed history, physical examination, and targeted investigations are necessary to determine the underlying etiology and ensure proper management. The following article is a comprehensive review outlining the various aspects of delirium. PMID- 22772925 TI - Study of dual angiogenic/neurogenic growth factors among Saudi autistic children and their correlation with the severity of this disorder. AB - OBJECTIVE: To investigate the role of 2 angiogenic/neurogenic growth factors, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) in Saudi children with autism. METHODS: The study included a total of 60 children that included 20 controls and 40 patients with a confirmed diagnosis of autism. The study was conducted in the Department of Physiology, Faculty of Medicine, King Saud University, and in the Autism Research and Treatment Center, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between May 2010 and April 2011. Collected blood plasma samples were analyzed for VEGF and PDGF. RESULTS: The levels of VEGF showed a non-significant change in autistic children compared with the control children (p=0.065). The levels of PDGF were significantly higher in autistic children compared with the control children (p=0.01). Furthermore, this increase was significantly more pronounced in children with severe autism as compared with children with mild autism (p=0.001), and it was not correlated to the severity of the disorder. CONCLUSION: A rise in PDGF may contribute to the pathophysiology of the disorder, either alone or in synergy with other neurotrophic factors to induce an angiogenic-neuroprotective effect. Plasma VEGF has no causative or compensatory contribution to the pathology of this disorder. PMID- 22772926 TI - Does maternal Helicobacter pylori infection increase the risk of occurrence of neural tube defects in newborns in Northern Iran? AB - OBJECTIVE: To determine the relation between maternal Helicobacter pylori (H. pylori) infection and the occurrence of neural tube defects (NTDs) in newborns. METHODS: This hospital-based case-control study was carried out in Dezyani Teaching Hospital, Gorgan, Northern Iran from April 2007 to March 2009. Thirty five mothers with NTD-affected newborns, and 53 mothers with healthy newborns were considered the cases and controls. A peripheral blood sample was obtained from all subjects, and H. pylori infections were tested by H. pylori serum antibody. The serum folic acid, vitamin B12, ferritin, and homocysteine concentrations were measured by laboratory tests. Data were analyzed using odds ratio (OR) and logistic regression. RESULTS: Forty-three percent of cases, and 26% of controls were positive for H. pylori IgG antibody, and this difference was not significant. The H. pylori seropositivity non significantly increased the risk of NTD-affected pregnancies (OR: 2.08; 95% confidence interval [CI]: 0.84 5.17, p=0.11). Serum vitamin B12 deficiency was detected in 17% of cases and 13% of controls, and folic acid deficiency in 17% of cases and 13% of controls (p=0.61). The H. pylori seropositivity was non significantly associated with low serum folate (OR 1.93 CI: 0.58-6.4, p=0.34) and ferritin (OR 1.24; CI: 0.42-3.60, p=0.68). CONCLUSION: Maternal H. pylori infection can increase the risk of occurrence of NTDs in newborns. PMID- 22772927 TI - The role of anemia in first simple febrile seizure in children aged 6 months to 5 years old. AB - OBJECTIVE: To assess the relationship between anemia and first simple febrile convulsion in patients 6 months to 5 years old. METHODS: This cross-sectional study was performed on 240 patients aged 6 months to 5 years old from 10 October 2010 to 15 December 2011 at Ghaem Hospital, Imam Reza Hospital, and Dr. Sheikh Hospital, Mashhad, Iran. Patients were divided into 2 groups: the control group who had fever without seizure, and the case group who had first simple febrile seizure. The anemia levels in both groups were evaluated and compared. RESULTS: The mean age of patients was 20.7+/-14.8 months. It was 20.53+/-15.07 for the case group, and 20.9+/-14.6 for the control group (p=0.74). The mean hemoglobin in the case group was 11.05+/-1.37, and 11.14+/-1.19 in the control group (p=0.58). Anemia was detected in 37.5% of the case group, and 36.7% of controls (p=0.89). CONCLUSION: There was no relationship between anemia and first simple febrile seizure. PMID- 22772928 TI - Frequency, severity and risk factors for restless legs syndrome in healthcare personnel. AB - OBJECTIVE: To evaluate the frequency, severity, and risk factors for restless legs syndrome (RLS) in healthcare personnel. METHODS: This cross-sectional study was performed at the Outpatient Family Medicine Clinic of Meram Medical Faculty in Konya, Turkey and included 354 healthcare personnel who were working at the Meram Medical Faculty Hospital between October 2010 and June 2011. The International RLS (IRLS) rating scale was used to calculate RLS severity. The RLS symptoms positive patients were investigated for neurological examination. RESULTS: Of all the participants, 277 (78.2%) were female. The overall prevalence of RLS according to the 4 essential criteria in the participating healthcare personnel was 15% (n=53) (16.9% male, 14.4% female). Gender (p=0.726) and age (p=0.197) were not significantly related to RLS. According to the International Restless Legs Syndrome Study Group (IRLSSG) the severity scale for RLS, of the RLS positive patients, 16% were classified as mild (n=8), 40% as moderate (n=21), and 44% as severe (n=24). Approximately, 54.7% of 53 RLS patients had a positive family history of the disorder. CONCLUSION: Restless leg syndrome is a treatable disorder; however, it is still widely misdiagnosed by physicians. The history of the patient and family is very important in the diagnosis of RLS. PMID- 22772929 TI - Depression. Does it affect the comprehension of receptive skills? AB - OBJECTIVE: To compare the comprehension of depressed and non-depressed male and female Iranian learners of English as a Foreign Language (EFL) in receptive skills, and to investigate whether inefficiency in learning English could be due to depression. METHODS: We selected 126 boys and 96 girls aged between 15 and 18 by simple random sampling from 2 high schools in Kerman, Iran to examine whether there was any significant relationship between depression and comprehension of receptive skills in males and females. We undertook this descriptive, correlational study between January and May 2011 in Kerman, Iran. After administration of the Beck Depression Inventory (BDI), we found that 93 students were non-depressed, 65 had minimal depression, 48 mild depression, and 16 suffered from severe depression. RESULTS: The correlation between participants' scores on listening and reading test with depression level indicated a significant relationship between depression and comprehension of both listening, and reading. Males had higher scores in both reading and listening. In listening, there was no significant difference among the levels of depression and males and females. Regarding the reading skill, there was no significant difference among levels of depression; however, the reading comprehension of males and females differed significantly. CONCLUSION: Learners who show a deficiency in receptive skills should be examined for the possibility of suffering from some degree of depression. PMID- 22772930 TI - Variable influence of the degree of smoking dependence on adult attention deficit/hyperactivity disorder in Iraqi medical students. AB - OBJECTIVE: To demonstrate the differences in the patterns of adult attention deficit/hyperactivity disorder (ADHD) symptoms among non, light, and heavy smokers. METHODS: A cross-sectional study involving 400 medical students (representing first to sixth year students) was conducted in the Department of Pharmacology, University of Al-Mustansiriya, Baghdad, Iraq from March to June 2011. The medical students completed a questionnaire containing the adult ADHD self-report scale (ASRS-screener) and the Fagerstrom Test for Nicotine Dependence (FTND). An ADHD score >=14 was considered positive. An FTND score >=6 signifies heavy smokers, and an FTND score <=5 signifies light smokers. RESULTS: Three hundred and sixty-one medical students completed the questionnaire, 16.6% reported ADHD symptoms (19.8% male, 12.1% females). Forty-five percent of ADHD adults were smokers; more than half of them were categorized as heavy smokers (51.8%). In comparison with non-smokers, heavy smokers displayed significant deterioration in their inattentive and total ASRS score (p=0.0001). Light smokers show significantly higher hyperactive symptoms in comparison with non-smokers (p=0.041). A high FTND score was associated with severer deterioration in inattentive (r=0.391, p=0.001) but not hyperactive symptoms (r=0.153, p=0.117). CONCLUSION: The ADHD symptoms are highly prevalent among Iraqi medical students, and smoking among ADHD students is higher and heavier than non-ADHD controls. Heavy smoking tends to deteriorate rather than ameliorate (self-medicate) ADHD symptoms. PMID- 22772931 TI - Intracranial calcifications, microcephaly, and seizure. If not congenital infection, what could it be? AB - Intracranial calcification has a variety of etiologies; among those are environmental and metabolic disturbances involving calcium homeostasis. The main environmental factors resulting in intracranial calcification are congenital infections with toxoplasmosis, and cytomegalovirus. There are increasing reports on cases showing pictures of congenital infection in the absence of confirmative positive TORCH screen, and there are many cases reported worldwide sharing the same presentation labeled as autosomal recessive congenital infection-like syndrome or pseudo-TORCH syndrome (OMIM 600158). PMID- 22772932 TI - Protracted disease course after deafness in a man with Brown-Vialetto-Van Laere syndrome. AB - Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare type of motor neuron disease, characterized by bilateral deafness, and multiple cranial nerve involvement. The disease is more frequent in females, but rapid deterioration was attributed to male gender or early onset. Herein, we report a man with BVVLS who had a longer than expected interval between onset of deafness and other motor symptoms that culminated to diagnosis. Six years later, he had gradual worsening and death. Along with potential new developing therapeutic options, this case emphasizes considering the diagnosis of BVVLS especially after a long period of stability, even in men. PMID- 22772933 TI - An ictal epilepsy case monitored by resting-state fMRI. AB - Most resting-state functional MRI studies of epilepsy are conducted in the interictal phase as the ictal phase is not suitable. We report and discuss a 13 year-old female epilepsy patient who had ictal examination. She was diagnosed with simple partial seizure epilepsy and on regular anti-epileptic drugs. There were no significant symptoms after careful treatment. We conclude that analysis of the amplitude of low frequency fluctuations may provide a useful tool in the functional MRI study of epilepsy. PMID- 22772934 TI - Magnetic resonance imaging of crossed cerebellar diaschisis and bright pulvinar in status epilepticus. AB - Crossed cerebellar diaschisis and bright pulvinar are rare in patients with status epilepticus. We present a case of a 53-year-old man who was found confused, incontinent, and nonverbal. The EEG findings were consistent with non convulsive status epilepticus. The brain MR images showed findings consistent with crossed cerebellar diaschisis and bright pulvinar. We report and discuss this case to increase the awareness of these MRI signs in confused and obtunded patients. PMID- 22772935 TI - Ramsay Hunt syndrome with multiple cranial neuropathies in a liver transplant recipient. AB - Ramsay Hunt syndrome is an infection of the head and neck caused by varicella zoster virus involving the facial nerve; less commonly, other cranial nerves might be involved. We report a case of Ramsay Hunt syndrome in an immune compromised patient, with classic facial nerve palsy and ipsilateral ear vesicles, which rapidly evolved to involve multiple cranial neuropathies, and improved dramatically with antiviral therapy and corticosteroids. Varicella zoster virus should be considered as a cause of multiple cranial neuropathies in an immune compromised patient, and abrupt treatment with acyclovir should be initiated once this diagnosis is suspected. PMID- 22772936 TI - Pathological laughter in a patient with a brain-stem epidermoid cyst. PMID- 22772937 TI - Intracranial inflammatory pseudotumor mimicking malignant neoplasm. PMID- 22772938 TI - Patient-reported side effects of lamotrigine during routine clinic visits. PMID- 22772939 TI - Pattern of patient referrals to a tertiary neurosurgery center in the central region of Saudi Arabia. PMID- 22772940 TI - A middle aged man with respiratory failure and weakness. PMID- 22772941 TI - The role of titanium nitride supports for single-atom platinum-based catalysts in fuel cell technology. AB - As a first step towards a microscopic understanding of single-Pt atom-dispersed catalysts on non-conventional TiN supports, we present density-functional theory (DFT) calculations to investigate the adsorption properties of Pt atoms on the pristine TiN(100) surface, as well as the dominant influence of surface defects on the thermodynamic stability of platinized TiN. Optimized atomic geometries, energetics, and analysis of the electronic structure of the Pt/TiN system are reported for various surface coverages of Pt. We find that atomic Pt does not bind preferably to the clean TiN surface, but under typical PEM fuel cell operating conditions, i.e. strongly oxidizing conditions, TiN surface vacancies play a crucial role in anchoring the Pt atom for its catalytic function. Whilst considering the energetic stability of the Pt/TiN structures under varying N conditions, embedding Pt at the surface N-vacancy site is found to be the most favorable under N-lean conditions. Thus, the system of embedding Pt at the surface N-vacancy sites on TiN(100) surfaces could be promising catalysts for PEM fuel cells. PMID- 22772942 TI - A study on epidemiological profile of anxiety disorders among people living with HIV/AIDS in a sub-Saharan Africa HIV clinic. AB - The aim of this study is to find out the prevalence, types and correlates of anxiety disorders among people living with HIV/AIDS (PLWHA) attending a sub Saharan Africa HIV clinic. Three hundred HIV positive adults were subjected to semi-structured clinical interview using the Schedule for Clinical Assessment in Neuropsychiatry to diagnose anxiety disorders in them. Additionally, a socio demographic/clinical profile questionnaire designed for the study was administered to the study participants. The prevalence of anxiety disorders among PLWHA in this study was 21.7 %, and anxiety disorder unspecified (6.2 %), mixed anxiety-depressive disorder (5.3 %) and social phobia (4 %) among others were the subtypes of anxiety disorders elicited among the participants. Lack of family support [correlation coefficient (r) = 0.212, P < 0.001], unemployment (r = 0.168, P = 0.004) and being unmarried (r = 0.182, P = 0.002) were much more likely to be found among participants with anxiety disorders; while younger age group (r = -0.126, P = 0.039) and negative previous mental illness (r = -0.894, P = 0.021) seem protective against anxiety disorders in this study. Our findings suggest a high burden of anxiety disorders among PLWHA and up to five-folds when compared to the general population. Thus, integration of proactive mental health screening as well as treatment services with inclusion of targeted intervention for anxiety disorders among PLWHA is recommended. PMID- 22772943 TI - [Total hip arthroplasty by neuromuscular impairment: functional outcome]. AB - INTRODUCTION: Studies which deal with the problems of total hip arthoplasty (THA) in patients with neuromuscular impairments are rare. The aim of this study was to examine whether THA for painful coxarthrosis in such patients relieved pain and improved functional outcome and how high the complication rate was. MATERIAL AND METHODS: For this study 10 patients (13 hips) with neuromuscular impairment who had received a total hip arthroplasty for painful coxarthrosis were retrospectively identified. A chart review determined the preoperative functional level. For postoperative evaluation all patients completed a questionnaire, including a self-created modified hip score. RESULTS: The average age of the patients at the time of follow-up was 42.1 years (range 26.5-62.2 years, standard deviation SD 9.9 years) and the minimum follow-up was 24 months (average 80.3 months, range 24-143 months, SD 47 months). Pain relief was obtained for all patients but two patients had a postoperative dislocation and four patients had a major complication (infection) requiring removal of the implant. Therefore, the follow-up rate at the final examination with completed questionnaires was 69% (9 out of 13 excluding patients with removal of THA). These patients showed an improved function from 42.2-83.66 points in the hip score (p=0.0006) and there was general satisfaction with the procedure. DISCUSSION: Total hip arthroplasty can provide improved function in patients with neuromuscular impairment and severe coxarthrosis. The rate of complications was moderate in this series; however, the high infection rate in these patients should be kept in mind. PMID- 22772944 TI - [Spinal epidural lipomatosis]. AB - Spinal epidural lipomatosis (SEL) is a rare condition affecting the thoracic and lumbar spine, characterized by a hypertrophy and hyperplasia of the rich vascularized fat tissue inside the spinal canal. The etiology of SEL is unknown. A high number of cases are associated with obesity, corticosteroid intake and a dysbalance in adrenocorticotropic hormone (ACTH)-cortisone metabolism. It can be an incidental radiographic finding or present with symptoms, such as low back pain, weakness of the lower limbs, dysesthesia, radiculopathy, claudication or even cauda equina syndrome. The interdisciplinary treatment consists of weight reduction, weaning from corticosteroids and in persisting cases or neurologic alterations in surgical decompression of the spinal canal. The following article presents a current review and a case report of this rare entity. PMID- 22772946 TI - CySBML: a Cytoscape plugin for SBML. AB - SUMMARY: CySBML is a plugin designed to work with Systems Biology Markup Language (SBML) in Cytoscape having the following features: SBML import, support of the SBML layout and qualitative model packages, navigation in network layouts based on SBML structure, access to MIRIAM and SBO-based annotations and SBML validation. CySBML includes an importer for BioModels to load SBML from standard repositories. AVAILABILITY AND IMPLEMENTATION: Freely available for non commercial purposes through the Cytoscape plugin manager or for download at http://sourceforge.net/projects/cysbml/. CONTACT: cysbml team@lists.sourceforge.net SUPPLEMENTARY INFORMATION: Tutorial, usage guide, installation instructions and additional figures are available for download at http://www.charite.de/sysbio/people/koenig/software/cysbml/. PMID- 22772945 TI - [Diffuse idiopathic skeletal hyperostosis: current aspects of diagnostics and therapy]. AB - Diffuse idiopathic skeletal hyperostosis (DISH) is a common but often unrecognized systemic disorder observed mainly in the middle-aged and elderly population, characterized by ankylosing formations of the spine and ossifications of peripheral ligaments, tendons and joint capsule insertion points (entheses). Despite the increase of prevalence with age, the condition often remains undiagnosed. It can be an asymptomatic incidental radiographic finding but can also manifest in several multiorgan complications, such as back and neck pain, restriction of mobility of the spine, peripheral joint affection, dysphagia, dyspnea, foreign body sensation, hoarseness, neurologic manifestations due to compression of the spinal cord, hyperuricemia, obesity, hypercholesterinemia and resulting cardiovascular comorbidities, implicating a multidisciplinary approach. The following article presents a current overview of the condition. PMID- 22772947 TI - TLM-Tracker: software for cell segmentation, tracking and lineage analysis in time-lapse microscopy movies. AB - MOTIVATION: Time-lapse imaging in combination with fluorescence microscopy techniques enable the investigation of gene regulatory circuits and uncovered phenomena like culture heterogeneity. In this context, computational image processing for the analysis of single cell behaviour plays an increasing role in systems biology and mathematical modelling approaches. Consequently, we developed a software package with graphical user interface for the analysis of single bacterial cell behaviour. RESULTS: A new software called TLM-Tracker allows for the flexible and user-friendly interpretation for the segmentation, tracking and lineage analysis of microbial cells in time-lapse movies. AVAILABILITY: The software package, including manual, tutorial video and examples, is available as Matlab code or executable binaries at http://www.tlmtracker.tu-bs.de. PMID- 22772948 TI - A sequence comparison and gene expression data integration add-on for the Pathway Tools software. AB - We present a plug-in for Pathway Tools, an integrated systems biology software to create, maintain and query Pathway/Genome Databases. Fully integrated into the graphical user interface and menu, this plug-in extends the application's functionality by the ability to create multiple sequence alignments, systematically annotate insertion sequence (IS) elements and analyse their activity by cross-species comparison tools. Microarray probes can be automatically mapped to target genes, and expression data obtained with these arrays can be transformed into input formats needed to visualize them in the various omics viewers of Pathway Tools. The plug-in API itself allows developers to integrate their own functions into the Pathway Tools menu. AVAILABILITY: Binaries are freely available for non-commercial users at http://genome.tugraz.at/PGDBToolbox/ and can be used on all platforms supported by Pathway Tools. A user guide is freely available at: http://genome.tugraz.at/PGDBToolbox/documentation.shtml. PMID- 22772949 TI - B lymphocyte inhibition of anti-tumor response depends on expansion of Treg but is independent of B-cell IL-10 secretion. AB - The mechanisms by which B lymphocytes inhibit anti-tumor immunity remain poorly understood. Murine EMT-6 mammary tumors grow readily in immune competent mice (BALB/c), but poorly in B-cell-deficient MU(-/-) BALB/c mice (BCDM). T regulatory cell (Treg) expansion and function were impaired in BCDM compared with BALB/c. In this study, we compared tumor growth, Treg cell proliferation, tumor lymphocyte infiltration and cytolytic T cell activity in BALB/c, BCDM and BCDM partially reconstituted with B cells by adoptive transfer (BCDM+B). Partial reconstitution of BCDM with adoptively transferred B cells restored EMT-6 tumor growth, which was independent of IL-10 secretion by B cells. Instead, high frequencies of intratumoral B cells were associated with increased recruitment and proliferation of Treg cells within the tumor microenvironment. The B-cell-dependent accumulation of Treg within the tumor microenvironment was associated with reduced tumor infiltration by CD49+ NK and CD8+ T cells and reduced cytotoxic T cell activity against EMT-6 targets. Our studies indicate that tumor-dependent immunosuppression of T-cell-mediated anti-tumor immunity is coordinated within the tumor microenvironment by B-cell-dependent cross talk with Treg cells, which does not require production of IL-10 by B cells. PMID- 22772950 TI - Coping strategies in melanoma patients. AB - An observational, questionnaire-based, cross-sectional study was performed to assess whether differences in coping behaviour (positive and negative strategies) between patients with either a recent diagnosis of malignant melanoma (MM) or with benign dermatological disease, were predictive of the diagnosis. Coping strategies were assessed with the German version of the stress-coping questionnaire (SVF 120) in 46 inpatients for whom surgery was planned at the Department of Dermatology, Medical University of Graz, Austria. Subjects were divided into two groups: patients with non-metastatic MM, and patients with benign dermatological diseases (controls). The risk for the diagnosis "melanoma" decreased with higher values of "situation control" (p = 0.007) and increased with higher values of resignation (p = 0.035) and trivialisation (p = 0.039). More-over, the risk for having a MM with thickness > 1 mm decreased in patients with higher values in positive coping strategies (p < 0.34). These results suggest differences in coping behaviour between patients with MM and those with benign skin diseases and, amidst patients with MM, between patients with different MM thickness; the results may hence lead to earlier, more specific and more effective psychological interventions to improve coping in patients with MM, as differences in coping behaviour seem to appear even in the non-metastatic stage of the disease. PMID- 22772951 TI - Early neutrophil-to-lymphocyte ratio reduction as a surrogate marker of prognosis in never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as first-line therapy. AB - PURPOSE: An inflammatory-immunological marker, neutrophil-to-lymphocyte ratio (NLR), was evaluated as a surrogate indicator for prognosis of advanced lung adenocarcinoma patients. METHODS: The subjects of this study were 199 never smokers with advanced lung adenocarcinoma, who were enrolled in a prospective randomized phase III study (First-SIGNAL) comparing gefitinib with gemcitabine plus cisplatin as first-line therapy. The values of NLR were assessed at two time points: at baseline (pretreatment) and on day 1 of the second cycle (posttreatment). RESULTS: A higher posttreatment NLR was associated with a worse tumor response (median posttreatment NLR, 1.56 for partial response, 1.64 for stable disease, and 2.70 for progressive disease; P < 0.001). The risk of progression was higher when the posttreatment NLR was higher [hazard ratio (HR) = 1.23, 95 % confidence interval (CI) 1.15-1.31; P < 0.001]. A high posttreatment NLR was associated with an increased risk of death (HR = 1.13, 95 % CI 1.06-1.21; P < 0.001). These associations did not differ according to treatment arms. When total patients were divided into four groups according to the cutoff points of pre- and posttreatment NLRs, those with a high pretreatment NLR that declined substantially after treatment showed improved survival compared with those with a high pretreatment NLR that remained high even after treatment (median overall survival, 22.0 and 15.8 months, respectively; P < 0.001). CONCLUSIONS: A high posttreatment NLR is associated with poor prognosis. An early reduction in the NLR after effective treatment may indicate survival improvement in the patients with poor prognosis. PMID- 22772952 TI - The impact of work nature, lifestyle, and obesity on health-related quality of life in Chinese professional drivers. AB - OBJECTIVE: To assess the association of work nature, lifestyle and obesity with health-related quality of life (HRQOL) in professional drivers. METHODS: A total of 3376 Chinese professional drivers aged 18 to 70 years were recruited to assess the HRQOL by SF-12 summary scores (Physical Component Summary [PCS]; Mental Component Summary [MCS]), and collect data for work nature, lifestyle, and body mass index. Factors associated with HRQOL were examined by multiphase regression analyses. RESULTS: Professional drivers reported poorer physical and mental HRQOL than the general population. Shift work and lorry driving had significant negative effect on HRQOL. Obesity was associated with lower PCS but higher MCS. CONCLUSIONS: HRQOL of professional drivers tended to be low, especially among lorry drivers and shift drivers. Health intervention programs should promote regular exercise, healthy eating, no smoking, and weight control, which are modifiable factors improving HRQOL. PMID- 22772953 TI - Do workplace and home protective practices protect farm workers? Findings from the "For Healthy Kids" study. AB - OBJECTIVE: To assess associations of protective workplace and home practices with pesticide exposure levels. METHODS: Using data from orchard workers in the Yakima Valley, Washington, we examined associations of workplace and home protective practices with (1) urinary metabolite concentrations of dimethylthiophosphate (DMTP) in adults and children aged 2 to 6 years and (2) azinphos-methyl levels in house and vehicle dust. RESULTS: Data were collected from 95 orchard workers and 94 children. Contrary to expectation, adult farm workers who wore boots or washed hands using hand sanitizer had higher concentrations of DMTP than those who did not. Children who attended daycare had higher DMTP concentrations than children who did not. CONCLUSIONS: Few workplace or home practices were associated with pesticide exposure levels; workers who used hand sanitizer had higher concentrations of DMTP, as did children who attended daycare. PMID- 22772954 TI - The impact of surveillance on weight change and predictors of change in a population-based firefighter cohort. AB - OBJECTIVE: To document weight changes in a population-based cohort of male career firefighters and evaluate the impact of health surveillance on subsequent participant behavior and body composition. METHODS: Body mass index, waist circumference, and body fat percentage were assessed longitudinally in 311 male firefighters. RESULTS: Firefighters who reported making no changes after the baseline assessment (42.1%) experienced a 0.64 +/- 3.1 kg average weight gain, whereas firefighters who reported making one or more health behavior change (ie, changing their diet, increasing their physical activity, or both; 52.1%) lost an average of -1.3 kg. CONCLUSIONS: Regular health surveillance may motivate some firefighters to make health behavior changes. Although it is not currently the norm, fire departments should provide firefighters with annual health assessments including body composition and fitness measures, consistent with those recommended by the fire service's Wellness and Fitness Initiative. PMID- 22772955 TI - Psychometric properties of Osteoporosis Knowledge Tool and self-management behaviours among Malaysian type 2 diabetic patients. AB - Osteoporosis is a major growing public health problem and it is clear that much needs to be done to bridge the gap between patients and practitioners. However, the educator must have a valid and reliable tool to evaluate the effectiveness of the teaching and learning that are done. Osteoporosis Knowledge Tool (OKT) provides an important strategy for healthcare professionals to start early intervention for patients who are at risk of osteoporosis. The aims of this study were to translate and examine the psychometric properties of the Malaysian version of the Osteoporosis Knowledge Tool (OKT-M) among 250 type 2 diabetes patients and to assess factors that affect diabetic patients' osteoporosis knowledge. The OKT English version was translated and validated using the internationally accepted and recommended methodology. The sensitivity and specificity of OKT-M was calculated using receiver operating characteristic curve analysis. The face and content validity showed acceptable results. Internal consistency, test-retest reliability, mean difficulty factor and discriminatory power values were 0.72, 0.83, 0.47 +/- 0.16 and 0.96, respectively. The cut-off point of the OKT-M to predict osteoporosis/osteopenia was 14 with optimal sensitivity (84.1%) and specificity (85.5%). Regression analysis revealed that health belief, self-efficacy and some demographic data had an impact on the OKT M. The findings of this validation study indicate that the OKT-M is a reliable and valid tool with good psychometric properties in the Malaysian setting. The OKT-M is an appropriate tool for application in clinical setting to identify patients need for a bone health-promoting intervention regarding lifestyle behaviour changes. PMID- 22772956 TI - Acculturation among Latino primary caregivers and physician communication: receipt of advice regarding healthy lifestyle behaviors. AB - The present study was part of a larger randomized controlled childhood obesity prevention trial based in 11 public recreation centers. The primary aim was to evaluate the effectiveness of a multi-level intervention to prevent the onset of overweight and obesity among children (5-8 years of age). However, the purpose of the current study was to identify sociodemographic variables, such as acculturation, that were associated with receipt of physician advice among Latino primary caregivers. Participants included 221 Latino primary caregivers and their children from San Diego, CA. Cross-sectional baseline data suggested that Latino children with private insurance were more likely to receive physician advice regarding their eating habits. Conversely, primary caregivers between the ages of 30-39 were less likely to receive physician advice regarding their child's eating habits. Current findings highlight the continued need to improve preventive efforts and reduce health disparities among a vulnerable population, such as Latinos. PMID- 22772957 TI - The intersections of Health and Human Rights. PMID- 22772958 TI - Intersection 3: health financing and other barriers to universal access. PMID- 22772959 TI - Intersection 4: building a community of health and human rights. PMID- 22772960 TI - Measuring the way forward in Haiti: grounding disaster relief in the legal framework of human rights. AB - This article provides results from an online survey of humanitarian workers and volunteers that was conducted in May and June 2010. The purpose of the survey was to understand how the humanitarian aid system adopts or incorporates human rights into its post-natural disaster work and metrics. Data collected from Haiti suggest that humanitarians have embraced a rights-based approach but that they do not agree about how this is defined or about what standards and indicators can be considered rights-based. This disagreement may reveal that humanitarians are aware of a mismatch between the rights-based approach to post-disaster humanitarian work and the legal framework of human rights. Using participation and accountability as examples, this article identifies and examines this mismatch and suggests that the humanitarian aid system should more fully embrace engagement with the human rights framework. To do so, the article concludes, humanitarian actors and the human rights community should have an open dialogue about the development of metrics that accurately reflect and monitor adherence to the legal framework of human rights. This would allow the humanitarian aid system to ensure its interventions enhance the capacity of the disaster-affected state to fulfill its human rights obligations, and would allow humanitarian and human rights actors alike to measure the impact of such interventions on the realization of human rights in post-natural disaster settings. PMID- 22772961 TI - Identification of human trafficking victims in health care settings. AB - BACKGROUND: An estimated 18,000 individuals are trafficked into the United States each year from all over the world, and are forced into hard labor or commercial sex work. Despite their invisibility, some victims are known to have received medical care while under traffickers' control. Our project aimed to characterize trafficking victims' encounters in US health care settings. METHODS: The study consisted of semi-structured interviews with six Key Informants who work closely with trafficking victims (Phase I) and 12 female trafficking survivors (Phase II). All survivors were recruited through the Coalition to Abolish Slavery and Trafficking, an NGO in Los Angeles, and all were trafficked into Los Angeles. Interviews were conducted in English and six other languages, with the assistance of professional interpreters. Using a framework analysis approach that focused on victims' encounters in health care settings, we assessed interview transcript content and coded for themes. We used an exploratory pile-sorting technique to aggregate similar ideas and identify overarching domains. RESULTS: The survivors came from 10 countries. Eight had experienced domestic servitude, three had survived sex trafficking, and one had experienced both. Half the survivors reported that they had visited a physician while in their traffickers' control, and another worked in a health care facility. All Key Informants described other victims who had received medical care. For domestic servants, medical visits were triggered by injury and respiratory or systemic illness, while sex trafficking victims were seen by health professionals for sexually transmitted infections and abortion. Trafficking victims were prevented from disclosing their status to health care providers by fear, shame, language barriers, and limited interaction with medical personnel, among other obstacles. DISCUSSION: This exploration of survivors' experiences in health care settings supports anecdotal reports that US health care providers may unwittingly encounter human trafficking victims. Increasing awareness of human trafficking, and modifying practice to facilitate disclosure, could improve victim identification. PMID- 22772962 TI - Intersection 1: rights and responsibilities amid climate change and environmental degradation. PMID- 22772963 TI - Fanm ayisyen pap kase: respecting the right to health of Haitian women and girls. AB - Only in recent years has violence against women begun to receive international attention as both a public health and human rights concern. This article argues that the right to be free from sexual violence is a fundamental component of the right to health, and the need is particularly acute in post-disaster contexts. This article uses post-earthquake Haiti as a case study to illustrate conditions for women and girls who suffer daily threats of physical, emotional, economic, and social harm in ways that have no direct parallels for their male counterparts. In addition, this article discusses the reasons that the humanitarian response in Haiti has not effectively protected women and girls and has instead exacerbated structural inequalities, making women, girls, and their families even more vulnerable to human rights violations including interference in their right to health. The article argues that the failure to guarantee the right of women to be free from sexual violence - an essential component of the right to health - is due in large part to the exclusion of displaced women from meaningful participation in formal humanitarian interventions. PMID- 22772964 TI - Lessons from the Chilean earthquake: how a human rights framework facilitates disaster response. AB - The earthquake of 2010 in Chile holds important lessons about how a rights-based public health system can guide disaster response to protect vulnerable populations. This article tells the story of Chile Grows With You (Chile Crece Contigo), an intersectoral system created three years before the earthquake for protection of child rights and development, and its role in the disaster response. The creation of Chile Grows With You with an explicit rights-oriented mandate established intersectoral mechanisms, relationships, and common understanding between governmental groups at the national and local levels. After the earthquake, Chile Grows With You organized its activities according to its founding principles: it provided universal access and support for all Chilean children, with special attention and services for those at greatest risk. This tiered approach involved public health and education materials for all children and families; epidemiologic data for local planners about children in their municipalities at-risk before the earthquake; and an instrument developed to assist in the assessment and intervention of children put at risk by the earthquake. This disaster response illustrates how a rights-based framework defined and operationalized in times of stability facilitated organization, prioritization, and sustained action to protect and support children and families in the acute aftermath of the earthquake, despite a change in government from a left-wing to a right-wing president, and into the early recovery period. PMID- 22772965 TI - Intersection 2: non-communicable diseases and global health equity. PMID- 22772966 TI - Denial of flood aid to members of the Ahmadiyya Muslim community in Pakistan. AB - During the catastrophic floods of 2010 in Pakistan, approximately 500 internally displaced families belonging to the Ahmadiyya sect of Islam were denied humanitarian relief. The failure of international agencies and Pakistan's government to protect basic human rights in the context of disaster relief raises profound questions. If all humanitarian work associated with natural disasters must be governed by canons of human rights, how should international agencies deal with legally empowered official discrimination? A review of the history of the Ahmadiyya community in Pakistan reveals decades of state-sanctioned persecution, particularly through its anti-blasphemy laws, and poses a serious challenge to the international community. When effective intervention is predicated on cooperation with state institutions, how can international relief agencies avoid becoming implicated in official discrimination? The denial of flood aid to Pakistan's Ahmadiyya community highlights the need for concerted action in disaster settings to prevent discrimination against vulnerable groups. Discriminatory legislation is not only a violation of basic norms enshrined in international compacts, it is a key problem for disaster relief. PMID- 22772967 TI - Concomitant aberrant methylation of p15 and MGMT genes in acute myeloid leukemia: association with a particular immunophenotype of blast cells. AB - In this study, methylation-specific polymerase chain reaction (MS-PCR) was used to define the methylation status of the target promoter sequences of p15 and MGMT genes in the group of 21 adult patients with acute myeloid leukemia (AML). The incidence of aberrant hypermethylation of p15 gene (71 %) was higher comparing to MGMT gene (33 %), whereas concomitant methylation of both genes had 24 % of the patients. Although the incidence of cytogenetic abnormalities between the groups with a different methylation status of p15 and/or MGMT genes was not significantly different, we observed general trend of clustering of abnormalities with adverse prognosis into groups with concomitant hypermethylation of both genes and only p15 gene. Also, we showed that AML patients with concomitant methylation of p15/MGMT genes had a higher proportion of leukemic blast cells characterized with specific expression of individual leukocyte surface antigens (CD117(+)/CD7(+)/CD34(+)/CD15(-)), indicating leukemic cells as early myeloid progenitors. Although we could not prove that hypermethylation of p15 and/or MGMT genes is predictive parameter for response to therapy and overall survival, we noticed that AML patients with comethylated p15/MGMT genes or methylated p15 gene exhibited a higher frequency of early death, lower frequency of complete remissions as well as a trend for shorter overall survival. Assessing of the methylation status of p15 and MGMT genes may allow stratification of patients with AML into distinct groups with potentially different prognosis. PMID- 22772968 TI - Hemostatic changes after 1 month of thalidomide and dexamethasone therapy in patients with multiple myeloma. AB - Thromboembolic events (TEE) are a serious clinical problem in multiple myeloma (MM) patients receiving thalidomide (T). Thirty-one MM patients were tested on diagnosis and after 2 and 4 weeks of therapy with T alone, or T in combination with dexamethasone (TD). Closure time (CT) in PFA-100 and P-selectin expression were assessed, as well as plasma levels of thrombin-antithrombin complexes (TAT), D-dimer (DD), soluble thrombomodulin (sTM) and von Willebrand factor antigen (vWF:Ag), along with the activity of coagulation factor VII and factor VIII. The concentration of vascular endothelial growth factor and its type 1 and 2 receptors were also assayed. On diagnosis, significantly prolonged median CT with both used cartridges, elevated P-selectin expression, DD concentration, TAT, vWF:Ag and factor VIII and factor VII activity were seen in the patient group as compared to controls. Therapy with these regimens caused marked shortening of CT with both cartridges. Treatment with TD leads to the significant increase in CD62P expression on platelets. Median TAT value increased significantly in relation to baseline after therapy with both regimens. Factor VIII activity exceeded 150 % in all patients after 2 weeks of TD therapy and was markedly elevated compared to baseline. One month of TD therapy significantly increased sTM concentration. These results demonstrate the enhanced platelet and coagulation system activation already present in MM patients on diagnosis, which is further increased by antimyeloma therapy. These changes are more pronounced after TD therapy and may promote TEE. Tested angiogenesis marker levels are elevated already on diagnosis, do not change after therapy and have no significant impact on the coagulation system in patients with MM. PMID- 22772969 TI - Examination of the relationship between chromosome abnormality in pituitary adenomas and tumor invasiveness by normal karyotype analysis and interphase fluorescence staining. AB - To study the potential relationship between chromosome abnormality and tumor invasiveness in pituitary adenomas. To use conventional R-band cytogenetic karyotype analysis and interphase fluorescence in situ hybridization using centromeric probe of chromosomes 8, 9, and 11 to detect chromosome abnormality in 30 cases of pituitary adenoma. All chromosomes except chromosomes 4, 16, and Y show significant variation between invasive and noninvasive pituitary adenomas. Chromosomes 8 and 12 display some type of numeric alteration in all endocrine subtypes of pituitary adenoma. Numeric alterations in chromosomes 9, 11, and 19 are more frequently detected in invasive pituitary adenomas compared with noninvasive tumors. Numeric alterations in chromosomes are common in all endocrine subtype pituitary adenomas. Furthermore, chromosome numbers are significantly different in invasive and noninvasive pituitary adenomas. On the basis of our study and literature review, we conclude that while chromosomes 8 and 12 may play important roles in the occurrence of pituitary adenomas, chromosomes 9, 11, and 19 may be specifically associated with invasiveness. PMID- 22772970 TI - A severe delayed infusion reaction induced by trastuzumab: a life-threatening condition. PMID- 22772971 TI - Discovering subgroups using descriptive models of adverse outcomes in medical care. AB - OBJECTIVES: Hospital discharge databases store hundreds of thousands of patients. These datasets are usually used by health insurance companies to process claims from hospitals, but they also represent a rich source of information about the patterns of medical care. The proposed subgroup discovery method aims to improve the efficiency of detecting interpretable subgroups in data. METHODS: Supervised descriptive rule discovery techniques can prove inefficient in cases when target class samples represent only an extremely small amount of all available samples. Our approach aims to balance the number of samples in target and control groups prior to subgroup discovery process. Additionally, we introduce some improvements to an existing subgroup discovery algorithm enhancing the user experience and making the descriptive data mining process and visualization of rules more user friendly. RESULTS: Instance-based subspace subgroup discovery introduced in this paper is demonstrated on hospital discharge data with focus on medical errors. In general, the number of patients with a recorded diagnosis related to a medical error is relatively small in comparison to patients where medical errors did not occur. The ability to produce comprehensible and simple models with high degree of confidence, support, and predictive power using the proposed method is demonstrated. CONCLUSIONS: This paper introduces a subspace subgroup discovery process that can be applied in all settings where a large number of samples with relatively small number of target class samples are present. The proposed method is implemented in Weka machine learning environment and is available at http://ri.fzv.uni-mb.si/ssd. PMID- 22772972 TI - The prevention of intimate partner violence. PMID- 22772973 TI - Incidental memory in dogs (Canis familiaris): adaptive behavioral solution at an unexpected memory test. AB - Memory processing in nonhuman animals has been typically tested in situations where the animals are repeatedly trained to retrieve their memory trace, such as delayed matching to sample, serial probe recognition, etc. In contrast, how they utilize incidentally formed memory traces is not well investigated except in rodents. We examined whether domestic dogs could solve an unexpected test based on a single past experience. In Experiment 1, leashed dogs were led to 4 open, baited containers and allowed to eat from 2 of them (Exposure phase). After a walk outside for more than 10 min, during which time the containers were replaced with new identical ones, the dogs were unexpectedly returned to the site and unleashed for free exploration (test phase). Eleven out of 12 dogs first visited one of the containers from which they had not eaten. In Experiment 2, two containers had food in them, one had a nonedible object, and the last one was empty. Dogs visited all 4 containers and were allowed to eat one of the food rewards in the Exposure phase. In the test phase, unleashed dogs first visited the previously baited container from which they had not eaten significantly more often than chance. These results demonstrate that in an unexpected, test dogs may retrieve "what" and "where" information about seen (now invisible) items from incidental memory formed during a single past experience. PMID- 22772974 TI - Common pitfalls in nanotechnology: lessons learned from NCI's Nanotechnology Characterization Laboratory. AB - The Nanotechnology Characterization Laboratory's (NCL) unique set-up has allowed our lab to handle and test a variety of nanoparticle platforms intended for the delivery of cancer therapeutics and/or imaging contrast agents. Over the last six years, the NCL has characterized more than 250 different nanomaterials from more than 75 different investigators. These submitted nanomaterials stem from a range of backgrounds and experiences, including government, academia and industry. This has given the NCL a unique and valuable opportunity to observe trends in nanoparticle safety and biocompatibility, as well as note some of the common mistakes and oversights of nanoformulation. While not exhaustive, this article aims to share some of the most common pitfalls observed by the NCL as they relate to nanoparticle synthesis, purification, characterization and analysis. PMID- 22772975 TI - Spike detection and clustering with unsupervised wavelet optimization in extracellular neural recordings. AB - Automatic and accurate detection of action potentials of unknown waveforms in noisy extracellular neural recordings is an important requirement for developing brain-computer interfaces. This study introduces a new, wavelet-based manifestation variable that combines the wavelet shrinkage denoising with multiscale edge detection for robustly detecting and finding the occurrence time of action potentials in noisy signals. To further improve the detection performance by eliminating the dependence of the method to the choice of the mother wavelet, we propose an unsupervised optimization for best basis selection. Moreover, another unsupervised criterion based on a correlation similarity measure was defined to update the wavelet selection during the clustering to improve the spike sorting performance. The proposed method was compared to several previously proposed methods by using a wide range of realistic simulated data as well as selected experimental recordings of intracortical signals from freely moving rats. The detection performance of the proposed method substantially surpassed previous methods for all signals tested. Moreover, updating the wavelet selection for the clustering task was shown to improve the classification performance with respect to maintaining the same wavelet as for the detection stage. PMID- 22772976 TI - Modeling of cell cultures in perfusion bioreactors. AB - Cultivating cells and tissues in bioreactors is a critical step in forming artificial tissues or organs prior to transplantation. Among various bioreactors, the perfusion bioreactor is known for its enhanced convection through the cell scaffold constructs. Knowledge of mass transfer is essential for controlling the cell culture process; however, obtaining this information remains a challenging task. In this research, a novel mathematical model is developed to represent the nutrient transport and cell growth in a 3-D scaffold cultivated in a perfusion bioreactor. Numerical methods are employed to solve the equations involved, with a focus on identifying the effect of factors such as porosity, culturing time, and flow rate, which are controllable in the scaffold fabrication and culturing process, on cell cultures. To validate the new model, the results from the model simulations were compared to the experimental results extracted from the literature. With the validated model, further simulations were carried out to investigate the glucose and oxygen distribution and the cell growth within the cell-scaffold construct in a perfusion bioreactor, thus providing insight into the cell culture process. PMID- 22772977 TI - Reclassification of Nocardioides basaltis Kim et al. 2009 as a later synonym of Nocardioides salarius Kim et al. 2008, and emendation of the species description. AB - The taxonomic relationship between Nocardioides salarius CL-Z59(T) and Nocardioides basaltis J112(T) was established. The 16S rRNA gene sequences of the type strains showed 99.6 % similarity. The DeltaT(m) for genomic DNA-DNA hybridization of N. salarius CL-Z59(T) and N. basaltis J112(T) was 0.6-1.6 degrees C, indicating that both strains belong to a single species. Phenotypic and chemotaxonomic characteristics showed no pronounced differences between the two species. Based on the results of the polyphasic approach, it is proposed that N. basaltis J112(T) is a later heterotypic synonym of N. salarius CL-Z59(T). An emended description of the species N. salarius is given. PMID- 22772978 TI - Anditalea andensis gen. nov., sp. nov., an alkaliphilic, halotolerant bacterium isolated from extreme alkali-saline soil. AB - A novel alkalophilic salt-tolerant rod-shaped bacterium, designated ANESC-S(T), was isolated from an extremely alkali-saline soil in the rural area of Anda city in northeast China. Taxonomic study using a polyphasic approach revealed that this non-motile, orange colony-forming microbe was Gram-negative and obligately aerobic. Optimal growth of strain ANESC-S(T) was achieved in the presence of NaCl with a concentration range of 0.5 to 4 % and pH between 7.5 and 9.2, and at temperatures ranging from 10 to 37 degrees C. Phylogenetic analysis of 16S rRNA sequences showed that of strain ANESC-S(T) is most homologous to Mongoliicoccus roseus MIM28(T) and Litoribacter ruber YIM CH208(T) with sequence similarity of 95.1 and 93.2 %, respectively. The genomic DNA G+C content of strain ANESC-S(T) was determined to be 39.1 mol%. The main isoprenoid quinone in ANESC-S(T) was found to be menaquinone-7. The main fatty acids were found to be iso-C(15:0) (27.5 %), iso-C(17:0)3-OH (14.0 %), anteiso-C(15:0) (9.8 %), summed feature 9 (iso-C(17:1)omega9c and/or 10-methyl C(16:0) 10.6 %) and summed feature 3 (C(16:1)w7c/C(16:1)w6c, 9.78 %). Based on the phenotypic, chemotaxonomic and phylogenetic data, strain ANESC-S(T) is considered to represent a new genus and species classified into the order Cytophagales, for which the name Anditalea andensis gen. nov., sp. nov. is proposed. The type strain is ANESC-S(T) (=CICC 10485(T) = NCCB 100412(T)). PMID- 22772979 TI - Mirror neuron activity during contagious yawning--an fMRI study. AB - Yawning is contagious. However, little research has been done to elucidate the neuronal representation of this phenomenon. Our study objective was to test the hypothesis that the human mirror neuron system (MNS) is activated by visually perceived yawning. We used functional magnetic resonance imaging to assess brain activity during contagious yawning (CY). Signal-dependent changes in blood oxygen levels were compared when subjects viewed videotapes of yawning faces as opposed to faces with a neutral expression. In response to yawning, subjects showed unilateral activation of their Brodmann's area 9 (BA 9) portion of the right inferior frontal gyrus, a region of the MNS. In this way, two individuals could share physiological and associated emotional states based on perceived motor patterns. This is one component of empathy (motor empathy) that underlies the development of cognitive empathy. The BA 9 is reportedly active in tasks requiring mentalizing abilities. Our results emphasize the connection between the MNS and higher cognitive empathic functions, including mentalizing. We conclude that CY is based on a functional substrate of empathy. PMID- 22772980 TI - Low rate of R132H IDH1 mutation in infratentorial and spinal cord grade II and III diffuse gliomas. PMID- 22772981 TI - Plane and simple: planar tetracoordinate carbon centers in small molecules. AB - A class of neutral 18-electron molecules with planar tetracoordinate carbon (ptC) centers is introduced. We show computationally that when n = 3 the neutral singlet molecule C(BeH)(n)(BH(2))(4-n) and other isoelectronic (18-valence electron) molecules of main group elements collapse from locally tetrahedral arrangements at the C-center to (near) planar tetracoordinate structures. For C(BeH)(3)BH(2) and C(CH(3))(BH(2))Li(2), for example, the tetrahedral type conformation is not even a minimum on the potential energy surface at the B3PW91, MP2(full), or CCSD levels of theory. The Mg analogue C(MgH)(3)BH(2) of the Be system also features a completely flat global minimum (with even higher energy planar minima in both cases as well). Other neutral compounds that may prefer planar geometries are apparent, and new openings for experimental investigations and theoretical analyses of planar tetracoordinate main group systems are identified. The planar conformation persists at one center in the C(BeH)(3)BH(2) dimer, and may be identifiable in higher order clusters of ptC molecules as well. PMID- 22772983 TI - Poly(A) binding protein nuclear 1 levels affect alternative polyadenylation. AB - The choice for a polyadenylation site determines the length of the 3' untranslated region (3'-UTRs) of an mRNA. Inclusion or exclusion of regulatory sequences in the 3'-UTR may ultimately affect gene expression levels. Poly(A) binding protein nuclear 1 (PABPN1) is involved in polyadenylation of pre-mRNAs. An alanine repeat expansion in PABPN1 (exp-PABPN1) causes oculopharyngeal muscular dystrophy (OPMD). We hypothesized that previously observed disturbed gene expression patterns in OPMD muscles may have been the result of an effect of PABPN1 on alternative polyadenylation, influencing mRNA stability, localization and translation. A single molecule polyadenylation site sequencing method was developed to explore polyadenylation site usage on a genome-wide level in mice overexpressing exp-PABPN1. We identified 2012 transcripts with altered polyadenylation site usage. In the far majority, more proximal alternative polyadenylation sites were used, resulting in shorter 3'-UTRs. 3'-UTR shortening was generally associated with increased expression. Similar changes in polyadenylation site usage were observed after knockdown or overexpression of expanded but not wild-type PABPN1 in cultured myogenic cells. Our data indicate that PABPN1 is important for polyadenylation site selection and that reduced availability of functional PABPN1 in OPMD muscles results in use of alternative polyadenylation sites, leading to large-scale deregulation of gene expression. PMID- 22772984 TI - MicroRNAs are exported from malignant cells in customized particles. AB - MicroRNAs (miRNAs) are released from cells in association with proteins or microvesicles. We previously reported that malignant transformation changes the assortment of released miRNAs by affecting whether a particular miRNA species is released or retained by the cell. How this selectivity occurs is unclear. Here we report that selectively exported miRNAs, whose release is increased in malignant cells, are packaged in structures that are different from those that carry neutrally released miRNAs (n-miRNAs), whose release is not affected by malignancy. By separating breast cancer cell microvesicles, we find that selectively released miRNAs associate with exosomes and nucleosomes. However, n miRNAs of breast cancer cells associate with unconventional exosomes, which are larger than conventional exosomes and enriched in CD44, a protein relevant to breast cancer metastasis. Based on their large size, we call these vesicles L exosomes. Contrary to the distribution of miRNAs among different microvesicles of breast cancer cells, normal cells release all measured miRNAs in a single type of vesicle. Our results suggest that malignant transformation alters the pathways through which specific miRNAs are exported from cells. These changes in the particles and their miRNA cargo could be used to detect the presence of malignant cells in the body. PMID- 22772985 TI - IBM1, a JmjC domain-containing histone demethylase, is involved in the regulation of RNA-directed DNA methylation through the epigenetic control of RDR2 and DCL3 expression in Arabidopsis. AB - Small RNA-directed DNA methylation (RdDM) is an important epigenetic pathway in Arabidopsis that controls the expression of multiple genes and several developmental processes. RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) and DICER-LIKE 3 (DCL3) are necessary factors in 24-nt small interfering RNA (siRNA) biogenesis, which is part of the RdDM pathway. Here, we found that Increase in BONSAI Methylation 1 (IBM1), a conserved JmjC family histone demethylase, is directly associated with RDR2 and DCL3 chromatin. The mutation of IBM1 induced the hypermethylation of H3K9 and DNA non-CG sites within RDR2 and DCL3, which repressed their expression. A genome-wide analysis suggested that the reduction in RDR2 and DCL3 expression affected siRNA biogenesis in a locus-specific manner and disrupted RdDM-directed gene repression. Together, our results suggest that IBM1 regulates gene expression through two distinct pathways: direct association to protect genes from silencing by preventing the coupling of histone and DNA methylation, and indirect silencing of gene expression through RdDM-directed repression. PMID- 22772986 TI - Phosphorothioate DNA as an antioxidant in bacteria. AB - Diverse bacteria contain DNA with sulfur incorporated stereo-specifically into their DNA backbone at specific sequences (phosphorothioation). We found that in vitro oxidation of phosphorothioate (PT) DNA by hydrogen peroxide (H(2)O(2)) or peracetic acid has two possible outcomes: DNA backbone cleavage or sulfur removal resulting in restoration of normal DNA backbone. The physiological relevance of this redox reaction was investigated by challenging PT DNA hosting Salmonella enterica cells using H(2)O(2). DNA phosphorothioation was found to correlate with increasing resistance to the growth inhibition by H(2)O(2). Resistance to H(2)O(2) was abolished when each of the three dnd genes, required for phosphorothioation, was inactivated. In vivo, PT DNA is more resistant to the double-strand break damage caused by H(2)O(2) than PT-free DNA. Furthermore, sulfur on the modified DNA was consumed and the DNA was converted to PT-free state when the bacteria were incubated with H(2)O(2). These findings are consistent with a hypothesis that phosphorothioation modification endows DNA with reducing chemical property, which protects the hosting bacteria against peroxide, explaining why this modification is maintained by diverse bacteria. PMID- 22772987 TI - Identification of new microRNA-regulated genes by conserved targeting in plant species. AB - MicroRNAs (miRNAs) are major regulators of gene expression in multicellular organisms. They recognize their targets by sequence complementarity and guide them to cleavage or translational arrest. It is generally accepted that plant miRNAs have extensive complementarity to their targets and their prediction usually relies on the use of empirical parameters deduced from known miRNA-target interactions. Here, we developed a strategy to identify miRNA targets which is mainly based on the conservation of the potential regulation in different species. We applied the approach to expressed sequence tags datasets from angiosperms. Using this strategy, we predicted many new interactions and experimentally validated previously unknown miRNA targets in Arabidopsis thaliana. Newly identified targets that are broadly conserved include auxin regulators, transcription factors and transporters. Some of them might participate in the same pathways as the targets known before, suggesting that some miRNAs might control different aspects of a biological process. Furthermore, this approach can be used to identify targets present in a specific group of species, and, as a proof of principle, we analyzed Solanaceae-specific targets. The presented strategy can be used alone or in combination with other approaches to find miRNA targets in plants. PMID- 22772988 TI - Preferred WMSA catalytic mechanism of the nucleotidyl transfer reaction in human DNA polymerase kappa elucidates error-free bypass of a bulky DNA lesion. AB - Human DNA Pol kappa is a polymerase enzyme, specialized for near error-free bypass of certain bulky chemical lesions to DNA that are derived from environmental carcinogens present in tobacco smoke, automobile exhaust and cooked food. By employing ab initio QM/MM-MD (Quantum Mechanics/Molecular Mechanics Molecular Dynamics) simulations with umbrella sampling, we have determined the entire free energy profile of the nucleotidyl transfer reaction catalyzed by Pol kappa and provided detailed mechanistic insights. Our results show that a variant of the Water Mediated and Substrate Assisted (WMSA) mechanism that we previously deduced for Dpo4 and T7 DNA polymerases is preferred for Pol kappa as well, suggesting its broad applicability. The hydrogen on the 3'-OH primer terminus is transferred through crystal and solvent waters to the gamma-phosphate of the dNTP, followed by the associative nucleotidyl transfer reaction; this is facilitated by a proton transfer from the gamma-phosphate to the alpha,beta bridging oxygen as pyrophosphate leaves, to neutralize the evolving negative charge. MD simulations show that the near error-free incorporation of dCTP opposite the major benzo[a]pyrene-derived dG lesion is compatible with the WMSA mechanism, allowing for an essentially undisturbed pentacovalent phosphorane transition state, and explaining the bypass of this lesion with little mutation by Pol kappa. PMID- 22772989 TI - Structural basis for translation termination by archaeal RF1 and GTP-bound EF1alpha complex. AB - When a stop codon appears at the ribosomal A site, the class I and II release factors (RFs) terminate translation. In eukaryotes and archaea, the class I and II RFs form a heterodimeric complex, and complete the overall translation termination process in a GTP-dependent manner. However, the structural mechanism of the translation termination by the class I and II RF complex remains unresolved. In archaea, archaeal elongation factor 1 alpha (aEF1alpha), a carrier GTPase for tRNA, acts as a class II RF by forming a heterodimeric complex with archaeal RF1 (aRF1). We report the crystal structure of the aRF1.aEF1alpha complex, the first active class I and II RF complex. This structure remarkably resembles the tRNA.EF-Tu complex, suggesting that aRF1 is efficiently delivered to the ribosomal A site, by mimicking tRNA. It provides insights into the mechanism that couples GTP hydrolysis by the class II RF to stop codon recognition and peptidyl-tRNA hydrolysis by the class I RF. We discuss the different mechanisms by which aEF1alpha recognizes aRF1 and aPelota, another aRF1 related protein and molecular evolution of the three functions of aEF1alpha. PMID- 22772990 TI - A common feature from different subunits of a homomeric AAA+ protein contacts three spatially distinct transcription elements. AB - Initiation of sigma(54)-dependent transcription requires assistance to melt DNA at the promoter site but is impeded by numerous protein-protein and nucleo protein interactions. To alleviate these inhibitory interactions, hexameric bacterial enhancer binding proteins (bEBP), a subset of the ATPases associated with various cellular activities (AAA+) protein family, are required to remodel the transcription complex using energy derived from ATP hydrolysis. However, neither the process of energy conversion nor the internal architecture of the closed promoter complex is well understood. Escherichia coli Phage shock protein F (PspF), a well-studied bEBP, contains a surface-exposed loop 1 (L1). L1 is key to the energy coupling process by interacting with Region I of sigma(54) (sigma(54)(RI)) in a nucleotide dependent manner. Our analyses uncover new levels of complexity in the engagement of a multimeric bEBP with a basal transcription complex via several L1s. The mechanistic implications for these multivalent L1 interactions are elaborated in the light of available structures for the bEBP and its target complexes. PMID- 22772992 TI - Winding single-molecule double-stranded DNA on a nanometer-sized reel. AB - A molecular system of a nanometer-sized reel was developed from F(1)-ATPase, a rotary motor protein. By combination with magnetic tweezers and optical tweezers, single-molecule double-stranded DNA (dsDNA) was wound around the molecular reel. The bending stiffness of dsDNA was determined from the winding tension (0.9-6.0 pN) and the diameter of the wound loop (21.4-8.5 nm). Our results were in good agreement with the conventional worm-like chain model and a persistence length of 54 +/- 9 nm was estimated. This molecular reel system offers a new platform for single-molecule study of micromechanics of sharply bent DNA molecules and is expected to be applicable to the elucidation of the molecular mechanism of DNA associating proteins on sharply bent DNA strands. PMID- 22772991 TI - The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle. AB - Recent genome-wide mapping of the mammalian replication origins has suggested the role of transcriptional regulatory elements in origin activation. However, the nature of chromatin modifications associated with such trans-factors or epigenetic marks imprinted on cis-elements during the spatio-temporal regulation of replication initiation remains enigmatic. To unveil the molecular underpinnings, we studied the human lamin B2 origin that spatially overlaps with TIMM 13 promoter. We observed an early G(1)-specific occupancy of c-Myc that facilitated the loading of mini chromosome maintenance protein (MCM) complex during subsequent mid-G(1) phase rather stimulating TIMM 13 gene expression. Investigations on the Myc-induced downstream events suggested a direct interaction between c-Myc and histone methyltransferase mixed-lineage leukemia 1 that imparted histone H3K4me3 mark essential for both recruitment of acetylase complex HBO1 and hyperacetylation of histone H4. Contemporaneously, the nucleosome remodeling promoted the loading of MCM proteins at the origin. These chromatin modifications were under the tight control of active demethylation of E box as evident from methylation profiling. The active demethylation was mediated by the Ten-eleven translocation (TET)-thymine DNA glycosylase-base excision repair (BER) pathway, which facilitated spatio-temporal occupancy of Myc. Intriguingly, the genome-wide 43% occurrence of E-box among the human origins could support our hypothesis that epigenetic control of E-box could be a molecular switch for the licensing of early replicating origins. PMID- 22772993 TI - Thermodynamic factors of natural selection in autocatalytic chemical systems. PMID- 22772994 TI - Tris-2(hydroxyethyl)ammonium (2-methylphenoxy)acetate as an inhibitor of synthesis of acid phospholipase A2 of mononuclear cells. PMID- 22772995 TI - Identification of the NtFZY gene family in tobacco (Nicotiana tabacum) involved in the tryptophan-dependent auxin biosynthesis pathway. PMID- 22772996 TI - Desmin and alpha-actinin-2 content in rat soleus muscle in the dynamics of gravitational unloading and subsequent reloading. PMID- 22772997 TI - The complex of zinc bis-(2-methylphenoxyacetate) with tris-2(hydroxyethyl) amine as an activator of synthesis of total tryptophanyl-tRNA synthetase. PMID- 22772998 TI - Thermoluminescence and conformational transitions in the primary processes of photosynthesis. PMID- 22772999 TI - Experimental proof of optimality of interfacing of chlorosome BChl c and membrane BChl a subantennae in superantenna of photosynthetic green bacteria from the oscillochloridaceae family. PMID- 22773000 TI - Bronsted acids bounded to the mitochondrial membranes as a substrate for ATP synthase. PMID- 22773001 TI - Glycine blocks the regulatory volume response of mouse oocytes to hypoosmotic stress. PMID- 22773002 TI - Enhancement of intrinsic protein luminescence in nanosized complex. PMID- 22773003 TI - Inhibition of mouse aging by using an essential oil composition. PMID- 22773004 TI - Long deletion hot spots inside retrotransposon 297. PMID- 22773005 TI - Two subsystems of meniscal collagen and their different thermal stabilities. PMID- 22773006 TI - N6-(benzyloxymethyl)adenosine is a novel anticytokinin, an antagonist of cytokinin receptor CRE1/AHK4 of Arabidopsis. PMID- 22773008 TI - Immunohistopathological changes in murine Schistosomiasis mansoni under the influence of N-acetyl-L-cysteine. AB - The main pathology associated with Schistosomiasis mansoni is granulomatous inflammation that may develop into hepatosplenic disease with fibrosis and hepatoesplenomegaly. It is known that N-acetyl-L-cysteine (NAC) reduces tissue damage in chronic liver diseases owing to its anti-inflammatory, antioxidant, and detoxifying properties. In this study, we investigated the imunohistopathological changes in murine schistosomiasis mansoni under the influence of NAC, in combination with Praziquantel (PZQ) or not. Three groups of mice were formed to evaluate the effects of NAC during infection in the acute, intermediate, and chronic phases. Each group was further subdivided into four subgroups: NAC, PZQ, NAC + PZQ and control (without treatment). Oral administration of NAC (200 mg/kg/day) was carried out on the first day after infection for the acute phase and on the 45th for the intermediate and chronic phases for 59 and 45, 75 days, respectively. PZQ (100 mg/kg/day), was given orally by gavage from the 45th to 49th day after infection. Histopathological analysis of liver tissue provided evidence that combined NAC + PZQ treatment reduced the development of granulomas observed in the chronic phase. Animals treated with NAC and/or PZQ showed a reduction in the size of granulomas and all those treated with NAC exhibited a lower degree of fibrosis. In all groups, NAC decreased the synthesis of interferon-gamma and nitric oxide, while increasing the levels of interleukin-10, but it did not influence the production of interleukin-4. On the whole, NAC treatment induced an immunomodulatory effect and reduced liver damage during the granulomatous inflammation in S. mansoni-infected mice. PMID- 22773009 TI - Ultrastructure and molecular phylogenetics of a new isolate of Pleistophora pagri sp. nov. (Microsporidia, Pleistophoridae) from Pagrus pagrus in Egypt. AB - The spore morphology and molecular systematic of a new microsporidian which was isolated from the common sea bream Pagrus pagrus (F: Sparidae Linnaeus, 1758) from the Red Sea, Egypt have been studied. Fifty-six out of 300 (18.7%) of this fish were infected with microsporidian parasites. The infection was appeared as whitish, ellipsoid, round, or elongated nodules embedded in the epithelial lining of the peritoneum and also in the intestinal epithelium. Light microscopic study revealed that nodules were encapsulated by a fibrous layer encircling numerous mature spores measuring 1.7 +/- 0.6 (1.5-2.7 MUm) * 1.5 +/- 0.3 MUm (1.2-1.8 MUm) in size. Ultrastructure of spores was characteristic for the genus Pleistophora: dimorphic, uninucleate spores (each spore possesses three to five polar filament coils) and a posterior vacuole. Also, the early recognizable stages of the parasite within nodules include uninucleated, binucleated, and multinucleated meronts followed by detachment of the plasmalemma of the sporont producing sporoblasts which mature to spores that consist of a spore coat and spore contents. Also, we analyzed the small subunit ribosomal gene (SSUrDNA) using PCR and sequencing specimens from the marine populations of P. pagrus fish from the Red Sea. From blast searches, sequence analysis, and phylogenetic analysis, we did not find corresponding GenBank entries to our species. Comparison of the nucleotide sequences showed that the sequence of our microsporidium was most similar to five Pleistophora species with degrees of identity (>91.5%). It was most similar (97.8% identity) to that of Pleistophora hyphessobryconis (account no. GU126672) differing in 19 nucleotide positions and with lower divergence value, Pleistophora ovariae (96.2% identity, account no. AJ252955), Pleistophora hippoglossoideos (91.9% identity, account no. AJ252953), Pleistophora mulleri (91.9% identity, account no. EF119339), and Pleistophora typicalis (91.9% identity, account no. AJ252956). So, they likely represent new species named Pleistophora pagri sp. n. with accession number JF797622 and a GC content of 53%. PMID- 22773010 TI - Efficacy of extracts of immature mango on ovine gastrointestinal nematodes. AB - The principal health problem in small ruminants is helminthiasis and the rapid development of nematode resistance to anthelminthics has limited the success of control in several countries, stimulating the search for alternatives. In this study, extracts of immature fruits of the mango Mangifera indica L. var Uba were evaluated for inhibition of larval development and fecal egg count reduction in sheep naturally infected with gastrointestinal nematodes. In the phytochemical analyses, tannins and flavonoids were the metabolites identified. Aqueous extracts of immature fruits at 100 mg ml(-1) showed 100 % inhibition of larval development. The LC(90) of the extract was 35.9 mg ml(-1) and the in vivo anthelminthic efficacy at 0.740 g kg(-1) (BW, orally) was 53 %. The identification of larvae showed that 99.8 % were Haemonchus spp. In vitro and in vivo results indicate that this fruit could assist ovine nematode control. PMID- 22773011 TI - Use of alternative medicine for weight loss among Mexican-American women. AB - The objective of this study is to examine the use of complementary and alternative medicine (CAM) for weight loss among Mexican-American women. Cross sectional survey of different CAM modalities, including traditional Mexican medicine therapies. The sample was drawn from women participating in a weight loss program in Portland, Oregon. Sample consisted of 31 adult Mexican-American women. Most respondents reported using some form of CAM for weight loss, with most reporting using herbs and teas (70 %), home remedies (61 %) and massage (55 %). Mexican-American women report using a wide range of CAM therapies for weight loss. Understanding their patterns of use will enhance cultural competence of health care professionals and help address their medical needs. PMID- 22773012 TI - A novel equation and nomogram including body weight for estimating prostate volumes in men with biopsy-proven benign prostatic hyperplasia. AB - Anthropometric measurements, e.g., body weight (BW), body mass index (BMI), as well as serum prostate-specific antigen (PSA) and percent-free PSA (%fPSA) have been shown to have positive correlations with total prostate volume (TPV). We developed an equation and nomogram for estimating TPV, incorporating these predictors in men with benign prostatic hyperplasia (BPH). A total of 1852 men, including 1113 at Tokyo Medical and Dental University (TMDU) Hospital as a training set and 739 at Cancer Institute Hospital (CIH) as a validation set, with PSA levels of up to 20 ng ml(-1), who underwent extended prostate biopsy and were proved to have BPH, were enrolled in this study. We developed an equation for continuously coded TPV and a logistic regression-based nomogram for estimating a TPV greater than 40 ml. Predictive accuracy and performance characteristics were assessed using an area under the receiver operating characteristics curve (AUC) and calibration plots. The final linear regression model indicated age, PSA, %fPSA and BW as independent predictors of continuously coded TPV. For predictions in the training set, the multiple correlation coefficient was increased from 0.38 for PSA alone to 0.60 in the final model. We developed a novel nomogram incorporating age, PSA, %fPSA and BW for estimating TPV greater than 40 ml. External validation confirmed its predictive accuracy, with AUC value of 0.764. Calibration plots showed good agreement between predicted probability and observed proportion. In conclusion, TPV can be easily estimated using these four independent predictors. PMID- 22773013 TI - Genetic variants in TP53 and MDM2 associated with male infertility in Chinese population. AB - The TP53, a transcriptional regulator and tumor suppressor, is functionally important in spermatogenesis. MDM2 is a key regulator of the p53 pathway and modulates p53 activity. Both proteins have been functionally linked to germ cell apoptosis, which may affect human infertility, but very little is known on how common polymorphisms in these genes may influence germ cell apoptosis and the risk of male infertility. Thus, this study was designed to test whether three previously described polymorphisms 72Arg>Pro (rs1042522) and the Ex2+19C>T (rs2287498) in TP53, and the 5' untranslated region (5' UTR) 309T>G (rs937283) in MDM2, are associated with idiopathic male infertility in a Chinese population. The three polymorphisms were genotyped using OpenArray assay in a hospital-based case-control study, including 580 infertile patients and 580 fertile controls. Our analyses revealed that TP53 Ex2+19C>T and MDM2 309T>G polymorphisms are associated with male infertility. Furthermore, we detected a nearly statistically significant additive interaction between TP53 rs2287498 and MDM2 rs937283 for the development of male infertility (P(interaction)=0.055). In summary, this study found preliminary evidence, demonstrating that genetic variants in genes of the TP53 pathway are risk factors for male infertility. PMID- 22773014 TI - Invited commentary. PMID- 22773015 TI - A surgical technique for minimally invasive plate osteosynthesis of clavicular midshaft fractures. AB - This study describes a minimally invasive plate osteosynthesis technique to treat acute displaced clavicular midshaft fractures using anterior-inferior plating. The technique assesses the fracture via a medial window and a lateral window without opening the fracture area itself. A 3.5-mm locking reconstruction plate is applied to fix the clavicle fracture, and reduction is achieved with a joystick technique using 2 threaded k-wires. The clinical outcomes of 19 patients with clavicle midshaft fractures treated using this technique are also described. PMID- 22773016 TI - DSA observation of hemodynamic response of femoral head with femoral neck fracture during traction: Can traction really increase the risk of osteonecrosis of the femoral head? PMID- 22773017 TI - APTF: anteroposterior tibiofibular ratio, a new reliable measure to assess syndesmotic reduction. AB - OBJECTIVES: To assess the accuracy of a new radiographic measurement of the distal tibia and fibula on the lateral view of the ankle in normal adults: the anteroposterior tibiofibular (APTF) ratio. METHOD: Thirty adults without history of trauma or disease of the ankle were included. Bilateral ankles were x-rayed with a true lateral view of the ankle. A line from the anterior tibial physis scar to the posterior tibial cortex, passing by the intersection of the physis and the fibula anterior cortex, was drawn. The APTF ratio was calculated as the ratio of the anterior segment to the posterior segment. The measurements were done by 3 independent evaluators. Intra- and interobserver reliability was obtained using intraclass correlation. RESULTS: The APTF ratio was 0.94 +/- 0.13 with a range of 0.63-1.31. Sex and age had no effect on the results. Inter- and intraobserver reliability was good to very good with an intraclass correlation between 0.6 and 0.8. A strong correlation between the left and the right APTF ratio was observed (r = 0.501 and P = 0.001). CONCLUSION: The distal tibiofibular joint anatomy in the sagittal plane can be accurately assessed with a new reliable radiographic measurement, the APTF ratio. The reduction of this joint during surgery can be confirmed with a true lateral view of the ankle. The anterior fibula cortex crosses the tibial physeal scar at the center of the line crossing this point and the anterior cortex of the tibia at the level of the physeal scar in the normal ankle. PMID- 22773018 TI - An alternative patellar fracture fixation: a biomechanical study. AB - OBJECTIVES: The purpose of this study is to compare open reduction and internal fixation of the patella with a locking plate and tension-band construct (PF) versus cannulated screws and tension-band fixation (SF). The hypothesis is that both constructs will have similar failure loads with simulated extension loading. METHODS: Transverse patellar fractures were created in 10 cadaveric pairs of legs and were fixed with either PF or SF. Dual-energy X-ray Absorptiometry (DXA) scans of all calcanei measured bone mineral density (BMD). Using an MTS 810 servohydraulic testing machine, each leg cycled to full extension 10 times before loading to failure. A differential variable reluctance transducer measured the distraction of the patella. Data were analyzed using paired t test analysis and bivariate analysis for Pearson correlation coefficients. RESULTS: There was no difference in the BMD between the PF and the SF groups (P = 0.367). No measurable differences occurred during the 10 cycles, and load at clinical failure was not significantly different between the 2 fixation groups (P = 0.38). Stiffness during the final loading cycle was significantly higher for the SF group (P = 0.008). Ultimate strength of fixation was significantly higher in PF group (P = 0.048). BMD was not correlated to the ultimate strength of SF (P = 0.112), but was correlated for PF (P = 0.025). CONCLUSIONS: Based on our results, PF provides comparable strength to SF, and it seems to be a safe and effective alternative to the current gold standard. PMID- 22773019 TI - Laser targeting with C-arm fluoroscopy: effect on image acquisition and radiation exposure. AB - OBJECTIVES: Reducing unnecessary radiation exposure from medical imaging is paramount. This study assessed whether a laser aiming guide for C-arm fluoroscopy reduced the number of exposures needed to obtain an acceptable image, thereby reducing total fluoroscopy time for hip, knee, and ankle fluoroscopy. METHODS: An obese cadaver was placed supine on a radiolucent surgical table. Images were obtained by licensed radiologic technologists using a calibrated OEC 9900 Elite C arm with laser targeting (LT) and without LT (NLT). Dosimeters were placed 1, 3, and 6 ft (30.5, 91.5, and 183 cm) away from the center of the C-arm at 90-degree angles at 2 levels, simulating thyroid and gonadal exposure. Posterior-anterior (PA) images of the bilateral lower extremities were obtained with each technician acquiring 24 centered images (hip, knee, and ankle) using both LT and NLT C-arm fluoroscopy. RESULTS: Total fluoroscopy time was reduced by 19% when using LT with a 39% reduction for the knee and a 29% reduction for the ankle. The addition of LT improved the likelihood of obtaining a centered image for knees and ankles but not for hips. The gonadal dosimetry data were significantly higher than the thyroid dosimetry badges at 1 ft. At the 3-ft zone, only trace amounts of radiation were detected; the 6-ft zone reported no radiation exposure in either group. CONCLUSIONS: LT helped with imaging knees and ankles with statistically significant reductions in fluoroscopy time and a statistically significant improvement of image quality defined as obtaining a centered PA image faster. The dosimetry badges detected minimal exposure at 3 ft and no detectable exposure at 6 ft at both levels. PMID- 22773020 TI - Attitudes towards requiring ignition interlocks for all driving while intoxicated offenders: findings from the 2010 HealthStyles Survey. AB - Ignition interlocks are effective in reducing recidivism among driving while intoxicated (DWI) offenders while installed on their vehicles. However, the devices are not widely used in the USA. This survey gauged public support for requiring ignition interlocks for all convicted DWI offenders including first time offenders. 69% of respondents supported such a policy. Support was lowest (38%) among persons who reported drinking and driving in the past 30 days. Multivariate regression analysis indicated that support varied little by region, community size or most measured individual characteristics. Persons who did not drink and drive were 80% more likely to support the requirement than those who drink and drive. These findings suggest that laws requiring ignition interlocks for all convicted DWI offenders may face the most opposition in communities with high levels of drinking and driving. PMID- 22773021 TI - Impact of population density on collision rates in a rapidly developing rural, exurban area of Los Angeles County. AB - OBJECTIVES: To determine if the commonly acknowledged relationships between population density and traffic collisions are found at the subcounty level and to describe how collision characteristics may vary substantially at a local level, with a particular emphasis on exurban areas. DESIGN: Los Angeles County collision data were obtained from the California Highway Patrol and the census tract and service planning area (SPA) for each collision were determined. The correlation between population density and collision rates by census tract was calculated within each SPA and for the entire county. Primary collision factors were compared for geographic areas of different population densities within one exurban SPA in Los Angeles County. RESULTS: An inverse relationship was found between collision rates and population density within Los Angeles County. Primary collisions factors were different in areas of the county with different population densities, with driving or biking under the influence particularly common in the most rural area. CONCLUSIONS: Subcounty analyses are very important to the study of traffic collisions. Traffic problems in rapidly developing exurban areas may be quite different from those in older, more established areas. PMID- 22773022 TI - The effect of spironolactone on ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators. AB - BACKGROUND: Previous studies have suggested that aldosterone blockade can reduce the incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients with heart failure. The SPIronolactone to Reduce ICD Therapy (SPIRIT) trial was designed to test the hypothesis that spironolactone reduces the incidence of VT/VF in patients with implantable cardioverter-defibrillators (ICDs) who are at moderately high risk for recurrent VT/VF. METHODS AND RESULTS: Ninety patients who had ICDs who were at moderately high risk for recurrent VT/VF and who were not candidates for spironolactone by current heart failure guidelines were randomized to receive spironolactone 25 mg daily or placebo in a double-blind fashion. All patients had previously received ICD therapy (shock or antitachycardia pacing) for VT/VF within 2 years of randomization or an ICD for secondary prevention of VT/VF within 6 months of randomization. The primary end point was time to first recurrence of VT/VF requiring ICD therapy. After a median follow-up of 35 months, the Kaplan-Meier probability estimates for VT/VF requiring ICD therapy were 68.7% in the placebo group and 84.7% in the spironolactone group. Compared with placebo, spironolactone was associated with a similar risk of VT/VF (hazard ratio, 1.01; 95% CI, 0.64-1.83; P=0.71). There was no significant difference between the median times to first VT/VF recurrence requiring ICD therapy in the 2 groups. CONCLUSIONS: In patients with ICDs who were at moderately high risk for recurrent VT/VF on account of a recent VT/VF event that was either sustained or treated by the ICD and who were not candidates for spironolactone by current heart failure guidelines, spironolactone did not delay the first recurrence of VT/VF or reduce the risk of recurrent VT/VF. PMID- 22773023 TI - Ablation of atrial fibrillation using novel 4-dimensional catheter tracking within autoregistered left atrial angiograms. AB - BACKGROUND: We describe a novel fluoroscopy coregistered, 4-dimensional catheter tracking technology (MediGuide Technology [MGT]) used for treatment of patients with atrial fibrillation. The aim of the study was to investigate (1) the feasibility of nonfluoroscopic catheter manipulation within dynamic left atrial chamber models; (2) the integration of the technology into an established electroanatomical mapping system; and (3) potential clinical impact. METHODS AND RESULTS: Forty-nine patients received atrial fibrillation ablation using MGT enabled NavX-EnSite. Matched patients ablated with a conventional NavX-EnSite system served as a control group. MGT was used for the deployment of diagnostic catheters within preacquired cine loops, for nonfluoroscopic chamber mapping within dynamic angiograms, and for 4-dimensional tagging of anatomical landmarks. Integration with the electroanatomical mapping system allowed correction of field distortions and a reference tool to detect and correct map shifts. Catheter ablation was done without MGT because the ablation catheter was not MGT enabled. MGT worked safely and stably in all 49 patients. Catheter deployment within the preacquired cine loops was successfully performed in 45 of 49 (92%) patients. Catheter tracking within dynamic left atrial angiograms allowed nearly nonfluoroscopic creation of NavX-EnSite geometries with subsequent computed tomography model registration in all 49 patients. Overall, MGT significantly reduced total procedural fluoroscopy time (median [quartiles]) from 31 minutes (25, 43 minutes) to 16 minutes (10, 23 minutes) and irradiation dose from 14 453+/-7403 to 7363+/-5827 cGy*cm(2) (mean+/-SD), respectively (P<0.001). CONCLUSIONS: MGT is a tracking technology that allows 4-dimensional visualization of dedicated catheters within moving chamber models. Integration of the MGT with an established electroanatomical mapping system provided algorithms to facilitate mapping in the electroanatomical mapping system environment. As a first measurable clinical impact, MGT was able to reduce fluoroscopy exposure by nearly 50%. PMID- 22773024 TI - A new technique involving a spherical stainless steel device to optimize positioning of the umbilicus. AB - BACKGROUND: Creating an aesthetically pleasing umbilicus may be challenging due to various factors that involve the patient limitations and suboptimal techniques available to the surgeon. Although many techniques aim to locate the umbilicus after abdominoplasty, none are ideal. The authors use a new technique involving a stainless steel spherical device for definite location of the new neo-umbilicus site. METHODS: Abdominoplasty with full muscle plication and umbilicoplasty was performed to test the effectiveness of this new technique that involves a stainless steel marble called the Umbilicator. It has a diameter of 1.5 cm and three 2-mm holes drilled 120 degrees apart in an equilateral triangle. The Umbilicator is secured to the inferior and superior dermis of the umbilical stalk to help identify the future location of the umbilicus on the abdominal skin. Once the marble is secured, the superior abdominal flap is redraped and trimmed, the suture is repaired, and the location of the umbilicus is determined by feeling for the smooth spherical surface bump with gentle downward pressure on the overlying abdominal skin located within the proximity of the umbilicus. RESULTS: The result of this technique produced a definitive means of identifying and delivering the umbilical stalk during abdominoplasty. This technique has been performed in 23 consecutive abdominoplasty procedures with no difficulties locating the umbilical stalk and no infections resulting from the procedure. CONCLUSIONS: Accurate identification of the umbilicus provides the ability to create an aesthetically pleasing neo-umbilicus, thus optimizing abdominoplasty results. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. PMID- 22773025 TI - Low-dose nicotine facilitates spatial memory in ApoE-knockout mice in the radial arm maze. AB - Here, we investigated the effects of nicotine on spatial memory in ApoE-knockout (ApoE-KO) and wild-type (WT) mice in a radial arm maze. Training occurred on three consecutive days and the test was performed on day 4, with one trial per day. Then on day 4, animals were administered nicotine (0.1, 0.25, 0.5, and 1.0 mg/kg) or the antagonist of nicotinic receptors (nAChRs) mecamylamine (MEC 2 mg/kg) alone or together with 0.1 mg/kg nicotine. The number of errors in the first eight choices was recorded. The results were that 0.1 mg/kg nicotine decreased errors in ApoE-KO mice, while 0.1 and 0.25 mg/kg nicotine reduced errors in WT mice, indicating that lower doses of nicotine elicit a memory improvement. In contrast, 1.0 mg/kg nicotine increased errors in WT mice, but not in ApoE-KO mice. MEC alone had no noticeable effect on errors in either strain of mice. However, co-administration of 0.1 mg/kg nicotine and MEC increased errors and reduced the effects of nicotine in WT mice, but not in ApoE-KO mice. Our study found a biphasic effect of nicotine in WT mice: it improves spatial memory at lower doses and impairs it at a higher dose. In ApoE-KO mice, nicotine improves memory at a low dose and has no effect at a higher dose, suggesting that the ApoE deficiency may influence the efficacy of nicotine. Moreover, a reversal of nicotinic effects with MEC was seen in WT mice, indicating the likelihood of the involvement of nAChRs in the spatial-memory response to nicotine. PMID- 22773026 TI - Relieving the pruritus of atopic dermatitis: a meta-analysis. AB - The goal of this study was to perform a meta-analysis on randomized controlled trials of topical therapies compared against their vehicles, and systemic therapies compared against their placebos, and to record how these therapies changed the magnitude of pruritus associated with atopic dermatitis. A systematic search of the literature was performed using Medline, Embase, and the Cochrane Controlled Clinical Trials Register, as well as follow-up references in retrieved articles. Data regarding the magnitude of the change in pruritus was extracted from eligible publications and categorized according to the type of treatment modality. Standard inverse variance fixed-effects meta-analysis was used to calculate the pooled estimates for randomized controlled trials falling under each type of treatment. Overall, the topical treatments were more successful at reducing atopic pruritus compared to the systemic treatments. Calcineurin inhibitors were the most effective antipruritic agent. PMID- 22773027 TI - Health and human rights. Editor's note. PMID- 22773028 TI - Health and human rights in scientific literature: a systematic review over a decade. AB - BACKGROUND: Over the past decades, the health and human rights movement has become a public health actor that cannot and should not be ignored when defining public health policies. Little has been published about the scientific contribution of the movement, be it in terms of volume, topics, content, diffusion channels, production, or target sites. OBJECTIVE: This article aims to characterize the scientific production of articles focusing on "health and human rights" and to describe its evolution over a decade. METHODS: A systematic review of the literature was done. The following databases were considered: Medline, Embase, BDSP, Wholis, Saphir, Rero and Web of Science. The analysis focused on English and French contributions published between January 1, 1999 and December 31, 2008. RESULTS: Nine hundred twenty eight articles, published in 377 different journals, were reviewed. Among these articles, 43.7% had been written by one author and 56.3% by two or more authors. Over the studied decade, the production volume increased threefold. Most frequent developed topics were related to health systems (18.3%), mental health (11.5%), HIV/AIDS (10.3%), reproductive health (9.2%). Emerging topics included: the rights of patients (2.7%), new technologies (2.5%), and handicap (2.5%). Studies were classified according to their design in social analysis (42.7%), reviews of the literature (19.8%), qualitative studies (17.9%), editorials (12.5%), epidemiological studies (6.8%). Most studies were published in public health (34.5%) and biomedical journals (29.0%), while some appeared in social science journals (4.7%). The studies were related to global issues/settings (43.9%) or more specifically to country settings, for example, the United States (9.3%), Great Britain (7.8%), South Africa (3.3%), Australia (3.0%), Canada (2.6%), France (2.3%), and India (1.9%). The authors were mainly from industrialized countries. CONCLUSION: The publication of articles on health and human rights issues is increasing, and new topics are being addressed. Yet more evidence-based studies might be necessary to scientifically strengthen the domain. PMID- 22773029 TI - Human rights and health disparities for migrant workers in the UAE. AB - Systematic violations of migrant workers' human rights and striking health disparities among these populations in the United Arab Emirates (UAE) are the norm in member countries of the Gulf Cooperation Council (GCC). Migrant laborers comprise about 90 percent of the UAE workforce and include approximately 500,000 construction workers and 450,000 domestic workers. Like many other GCC members countries, the UAE witnessed an unprecedented construction boom during the early 2000s, attracting large numbers of Western expatriates and increasing demand for cheap migrant labor. Elite Emiratis' and Western expatriates' dependence on household staff further promoted labor migration. This paper offers a summary of existing literature on migrant workers and human rights in the UAE, focusing on their impact on related health ramifications and disparities, with specific attention to construction workers, domestic workers, and trafficked women and children. Construction workers and domestic laborers are victims of debt bondage and face severe wage exploitation, and experience serious health and safety problems resulting from inhumane work and living conditions. High rates of physical, sexual, and psychological abuse impact the health of domestic workers. Through a review of available literature, including official reports, scientific papers, and media reports, the paper discusses the responsibility of employers, governments, and the global community in mitigating these problems and reveals the paucity of systematic data on the health of migrant workers in the Gulf. PMID- 22773030 TI - International law, national policymaking, and the health of trafficked people in the UK. AB - BACKGROUND: Human trafficking has been recognized both by the international community and many individual states around the world as a serious violation of human rights. Trafficking is associated with extreme violence and a range of physical, mental, and sexual health consequences. Despite the extreme nature of the harm caused by human trafficking, harm is not a concept that is integrated in the definition of trafficking or in policies to address the health of trafficked people. This paper examines the United Kingdom's response to human trafficking as a case study to explore national policy responses to the health needs of trafficked people and assess the willingness of UK authorities to implement international and regional law in securing trafficked people's health rights. METHODS: Between 2007 and 2010, data on the development of the UK response to trafficking were obtained through 46 interviews with key trafficking policy stakeholders and health care providers, participant observation at 41 policy relevant events, and document collection. Framework analysis was used to analyze the data. RESULTS: International and regional instruments specifically protect the health rights of trafficked people. Yet, UK engagement with trafficked people's health rights has been limited to granting, under certain circumstances, free access to health care services. Changes to trafficked people's entitlements to free health care occurred following the ratification of the Council of Europe Convention on Action Against Trafficking in Human Beings, but had limited impact on trafficked people's access to medical care. CONCLUSIONS: International and regional instruments that provide specific or mandated instruction about states' health care obligations can be effective in furthering the health rights of vulnerable migrant groups. The UK government has demonstrated limited appetite for exceeding its minimum obligations to provide for the health of trafficked people, however, and key principles for promoting the health rights of trafficked people are yet to be fulfilled. PMID- 22773031 TI - The right to water in rural Punjab: assessing equitable access to water in the context of the ongoing Punjab Rural Water Supply Proejct. AB - Although India is poised to meet its Millennium Development Goal for providing access to safe drinking water, there remains a worrying discrepancy in access between urban and rural areas. In 2006, 96% of the urban population versus 86% of the rural population obtained their drinking water from an improved water source. To increase access to potable water in rural areas, the World Bank and the state of Punjab have implemented the Punjab Rural Water Supply and Sanitation Project (PRWSS) to improve or construct water supply systems in 3,000 villages deemed to have inadequate access to clean drinking water. This study aimed to examine whether the right to water was fulfilled in six towns in rural Punjab during implementation of the PRWSS. The normative content of the right to water requires that water be of adequate quantity, safety, accessibility, affordability, and acceptability in terms of quality. While our findings suggest that the PRWSS improved water quality, they also indicate that access to water was limited due to affordability and the low socioeconomic status of some people living in the target communities. PMID- 22773032 TI - The health and human rights of survivors of gun violence: charting a research and policy agenda. AB - The health and human rights implications of violently acquired impairments (VAI), specifically gun-related injuries and trauma resulting in disability, represent an overlooked public policy concern. For several decades, detailed attention has been committed to better understanding of the international arms trade and its consequences. A discursive shift in the last decade from "small arms control" as the core objective (a "hardware" focus on the weapons themselves) to "armed violence prevention" (a focus on impacts, wider drivers, and solutions) still requires a rigorous set of objectives that respond to the rights and needs of survivors of such violence. This article seeks to chart some of the challenges of responding to gun violence survivors and identify entry points for contributions from health, social science and human rights researchers and practitioners. Efforts to address armed violence typically pivot around two goals: reduction and prevention. But what of those already injured? This article argues that a third goal is overdue for attention: response to those injured, impaired, and disabled from gun violence. This would allow a clear pathway for progress (conceptual, political, policy, and practice) to be defined related to gun violence under the ambit of three overarching goals: reducing existing gun violence; responding to those already injured, traumatized, and impaired by such violence; and preventing future violence from occurring. PMID- 22773033 TI - Human rights, mental illness, and HIV: the Luthando Neropsychiatric HIV Clinic in Soweto, South Africa. AB - HIV is the leading infectious killer of adults in the world today and a majority of persons with HIV live in southern Africa. Mental illness is common among patients with HIV. Persons with HIV and mental illness, however, are often denied access to HIV treatment for a variety of reasons, including presumed non adherence, potential drug interactions, and lack of coordinated care. The exclusion of the mentally ill from HIV care is a concerning human rights issue. This paper discusses some of the human rights issues in the care of patients with mental illness and HIV and describes a successful model for integrated care developed at the Luthando Neuropsychiatric HIV Clinic in Soweto, South Africa. The Luthando clinic has provided care to more than 500 patients and has been shown to be a successful model for other programs to improve HIV care among the mentally ill. PMID- 22773034 TI - Developing a human rights-based program for tuberculosis control in Georgian prisons. AB - Tuberculosis (TB) is one of the leading infectious killers of adults globally. Incarcerated individuals represent a vulnerable population when it comes to TB exposure, development of disease, and poor treatment outcomes. The TB pandemic in prisons is a serious human rights issue, and multiple global organizations have called for human rights-based strategies to address it. There are, however, few countries implementing such programs on the ground. Georgia, a former Soviet republic located in the Caucasus Mountains, has high rates of TB and a large prison population. This paper describes a needs assessment carried out in one prison in Georgia and the human rights-based strategy being implemented by the Georgian National TB Program to address TB control in the prison setting. It is hoped that the proposed program can serve as a model for other countries with high rates of TB among incarcerated individuals. PMID- 22773035 TI - Palladium-catalysed heteroannulation of [60]fullerene with N-benzyl sulfonamides and subsequent functionalisation. AB - The palladium-catalysed heteroannulation of [60]fullerene with various N-benzyl sulfonamides via C-H bond activation affords [60]fullerene-fused tetrahydroisoquinolines. In the presence of a Bronsted acid [60]fullerene-fused tetrahydroisoquinolines are transformed to [60]fullerene-fused indanes, in which the sulfonamide group can be removed or replaced with an aryl group. PMID- 22773036 TI - Does the surface-treated AN69 membrane prolong filter survival in CRRT without anticoagulation? AB - PURPOSE: The need for continuous anticoagulation remains a significant drawback in continuous renal replacement therapy (CRRT), especially in patients with increased bleeding risk. Polyethyleneimine treatment of the AN69 membrane (AN69ST) reduces thrombogenicity through decreased contact activation and promotion of heparin binding. The aim of this study is to evaluate whether this membrane prolongs filter survival in CRRT without anticoagulation. METHODS: A single-center, prospective, randomized, double-blind controlled trial with cross over design comparing filter survival with the AN69ST membrane and the original AN69 membrane in 39 patients treated with continuous venovenous hemofiltraton (CVVH) without additional heparin. RESULTS: Filter survival with the AN69ST membrane (n = 75) was 14.2 +/- 8.2 h, which is not significantly different from the 13.3 +/- 10.3 h for the original AN69 membrane (n = 76; p = 0.59). Limiting the analysis to those treatments that were interrupted for filter clotting yielded similar results: 14.4 +/- 8.2 h for the AN69 ST membrane (n = 62) versus 14.1 +/- 7.5 h for the original AN69 membrane (n = 56) (p = 0.93). CONCLUSIONS: Compared with the original AN69 membrane, the surface-treated AN69ST membrane does not prolong filter survival during CVVH without systemic anticoagulation and with the CRRT settings used in this study. PMID- 22773037 TI - Heart transplantation for acute cardiac failure caused by thrombotic thrombocytopenic purpura (TTP). PMID- 22773038 TI - Statistical process control for monitoring standardized mortality ratios of a classification tree model. AB - OBJECTIVES: The ratio of observed to expected mortality (standardized mortality ratio, SMR), is a key indicator of quality of care. We use PreControl Charts to investigate SMR behavior over time of an existing tree-model for predicting mortality in intensive care units (ICUs) and its implications for hospital ranking. We compare the results to those of a logistic regression model. METHODS: We calculated SMRs of 30 equally-sized consecutive subsets from a total of 12,143 ICU patients aged 80 years or older and plotted them on a PreControl Chart. We calculated individual hospital SMRs in 2009, with and without repeated recalibration of the models on earlier data. RESULTS: The overall SMR of the tree model was stable over time, in contrast to logistic regression. Both models were stable after repeated recalibration. The overall SMR of the tree on the whole validation set was statistically significantly different (SMR 1.00 +/- 0.012 vs. 0.94 +/- 0.01) and worse in performance than the logistic regression model (AUC 0.76 +/- 0.005 vs. 0.79 +/- 0.004; Brier score 0.17 +/- 0.012 vs. 0.16 +/- 0.010). The individual SMRs' range in 2009 was 0.53-1.31 for the tree and 0.64 1.27 for logistic regression. The proportion of individual hospitals with SMR >1, hinting at poor quality of care, reduced from 38% to 29% after recalibration for the tree, and increased from 15% to 35% for logistic regression. CONCLUSIONS: Although the tree-model has seemingly a longer shelf life than the logistic regression model, its SMR may be less useful for quality of care assessment as it insufficiently responds to changes in the population over time. PMID- 22773039 TI - Expression of MSP58 in human colorectal cancer and its correlation with prognosis. AB - We had reported that MSP58 regulates colorectal cancer cell proliferation, development, and apoptosis, by the cyclin D1-cyclin-dependent kinase 4-p21 pathway. In this study, MSP58 protein expression was examined by immunohistochemistry in 499 specimens of CRC. The relationship between various clinicopathological features and overall patient survival rate was analyzed. The association of MSP58 expression with the 499 CRC patients' survival rate was assessed by Kaplan-Meier and Cox regression. Using ROC curve to provide sensitivity and specificity of the score of MSP58 predicts local recurrence and survival of CRC patients. The expression of MSP58 was positively correlated with the depth of invasion (P < 0.001), local recurrence (P = 0.008), tumor grade (P = 0.002), and UICC stage (P < 0.001). The Kaplan-Meier survival analysis demonstrated that the survival time of CRC patients with low expression of MSP58 was longer than those with high expression during the 5-year follow-up period (P < 0.001). COX regression analysis indicated that high expression of MSP58 (P < 0.001), depth of invasion >pT(1) (P = 0.008), distant organ metastasis (pM(1)) (P < 0.001), regional lymph node metastasis (>= pN(1)) (P < 0.001), and local recurrence (Yes) (P = 0.007) were independent, poor prognostic factors of CRC. ROC curve showed the score of MSP58 expression level did provide a maximal sensitivity and specificity to predict local recurrence and survival of CRC patients. Our results demonstrated MSP58 might serve as a novel prognostic marker that is independent of, and additive to, the UICC staging system. PMID- 22773040 TI - Long-term outcome of continuous 5-fluorouracil/cisplatin-based chemotherapy followed by chemoradiation in patients with resected gastric cancer. AB - Despite substantial developments in gastric cancer treatment, the majority of patients relapse after definitive surgery. We have previously described well tolerated adjuvant regimen that includes a combination of bolus 5-fluorouracil, continuous 5-fluorouracil, and cisplatin followed by chemoradiation after 3 months of chemotherapy. The aim of this study was to evaluate long-term outcomes of patients treated with this regimen and to determine whether expressions of the excision repair cross-complementing (ERCC1) and thymidylate synthase (TS) predict clinical outcome in those patients. The study population consisted of 36 advanced gastric cancer patients. Patients were treated with six cycles of continuous 5 fluorouracil (600 mg/m(2)) for 24 h, push 5-fluorouracil (400 mg/m(2)), and leucoverin (LCV) (200 mg/m(2)) on day 1-2 every 2 weeks, cisplatin (60 mg/m(2)) on day 1 every 4 weeks followed by combined modality therapy using 45 Gy at 1.8 Gy per day concomitant with weekly bolus 5-fluorouracil (600 mg/m(2)) and LCV (50 mg). After median follow-up of 48.9 months, the median disease-free survival was 45 months and the overall survival was 66.4 months. Sixteen patients (44 %) were alive and disease-free. There was no significant correlation between ERCC1 expression and TS expression pattern and time to relapse (P = 0.302 and P = 0.707, respectively). In conclusion, long-term follow-up demonstrates that postoperative chemoradiation with combination of bolus 5-fluorouracil, continuous 5-fluorouracil, and cisplatin is a feasible approach. PMID- 22773041 TI - Identification of a new insertion in exon 20 of EGFR in a woman with NSCLC. AB - Mutations of epidermal growth factor receptor 1 (EGFR) gene occur in about 15 % of all NSCLCs in Western Europe and are frequently located in exons 19 and 21, being associated with high sensitivity to EGFR tyrosine kinase inhibitors (TKIs). By contrast, exon 20 insertions account for up to 10 % of all EGFR mutations and are correlated to EGFR TKI resistance. Herein, we describe a novel mutation in EGFR exon 20 in a female non-smoker bearing a lung adenocarcinoma, characterized by the insertion of a nucleotide triplet GTT, which translates into a protein with an additional Valine between Proline 772 and Histidine 773 (p.P772_H773insV c.2316_2317insGTT). The patient was treated with cisplatin/pemetrexed 1st-line and docetaxel 2nd-line chemotherapies, reporting a prolonged disease stabilization of 25 months. The identification and the biological and clinical characterization of novel EGFR mutations represent a prerequisite for their wide use as predictive biomarkers for personalized therapy in NSCLC. PMID- 22773042 TI - Gelatin methacrylate as a promising hydrogel for 3D microscale organization and proliferation of dielectrophoretically patterned cells. AB - Establishing the 3D microscale organization of cells has numerous practical applications, such as in determining cell fate (e.g., proliferation, migration, differentiation, and apoptosis) and in making functional tissue constructs. One approach to spatially pattern cells is by dielectrophoresis (DEP). DEP has characteristics that are important for cell manipulation, such as high accuracy, speed, scalability, and the ability to handle both adherent and non-adherent cells. However, widespread application of this method is largely restricted because there is a limited number of suitable hydrogels for cell encapsulation. To date, polyethylene glycol-diacrylate (PEG-DA) and agarose have been used extensively for dielectric patterning of cells. In this study, we propose gelatin methacrylate (GelMA) as a promising hydrogel for use in cell dielectropatterning because of its biocompatibility and low viscosity. Compared to PEG hydrogels, GelMA hydrogels showed superior performance when making cell patterns for myoblast (C2C12) and endothelial (HUVEC) cells as well as in maintaining cell viability and growth. We also developed a simple and robust protocol for co culture of these cells. Combined application of the GelMA hydrogels and the DEP technique is suitable for creating highly complex microscale tissues with important applications in fundamental cell biology and regenerative medicine in a rapid, accurate, and scalable manner. PMID- 22773043 TI - FhCaBP4: a Fasciola hepatica calcium-binding protein with EF-hand and dynein light chain domains. AB - In trematodes, there is a family of proteins which combine EF-hand-containing domains with dynein light chain (DLC)-like domains. A member of this family from the liver fluke, Fasciola hepatica-FhCaBP4-has been identified and characterised biochemically. FhCaBP4 has an N-terminal domain containing two imperfect EF-hand sequences and a C-terminal dynein light chain-like domain. Molecular modelling predicted that the two domains are joined by a flexible linker. Native gel electrophoresis demonstrated that FhCaBP4 binds to calcium, manganese, barium and strontium ions, but not to magnesium or zinc ions. The hydrophobic, fluorescent probe 8-anilinonaphthalene-1-sulphonate bound more tightly to FhCaBP4 in the presence of calcium ions. This suggests that the protein undergoes a conformational change on ion binding which increases the number of non-polar residues on the surface. FhCaBP4 was protected from limited proteolysis by the calmodulin antagonist W7, but not by trifluoperazine or praziquantel. Protein protein cross-linking experiments showed that FhCaBP4 underwent calcium ion dependent dimerisation. Since DLCs are commonly dimeric, it is likely that FhCaBP4 dimerises through this domain. The molecular model reveals that the calcium ion-binding site is located close to a key sequence in the DLC-like domain, suggesting a plausible mechanism for calcium-dependent dimerisation. PMID- 22773045 TI - Chewing lice (Insecta, Phthiraptera) and feather mites (Acari, Astigmata) associated with birds of the Cerrado in Central Brazil. AB - The association of chewing lice and feather mites with wild birds of riparian forest was investigated in the Cerrado biome, Tocantins State, Brazil. The birds were captured with mist nets between July 2008 and March 2009. Ectoparasites were collected by the dust-ruffling technique. Infestation rates were determined by the sampling prevalence, abundance, and mean intensity of ectoparasites. A total of 1,479 chewing lice were collected that were distributed in 3 families and 18 genera, of which 15 taxa were identified to the species level. Sixteen genera of feather mites were found, and 10 species were identified. A high prevalence rate of chewing lice and feather mites was found in non-Passeriformes (66.7 and 50.0%) and Passeriformes (57.8 and 75.6%) birds. New host-parasite associations were registered for two species of chewing lice and for four species of feather mites, thus expanding the geographical distribution in Brazil of six chewing lice species. This is the first study of the ectoparasites of wild birds to be conducted in this region of Brazil. PMID- 22773044 TI - Ultrastructure, development, and molecular phylogeny of Pleistophora hyphessobryconis, a broad host microsporidian parasite of Puntius tetrazona. AB - A potentially fatal microsporidial infection targeting the skeletal muscles of the tiger barb Puntius tetrazona was described. Ultrastructural and molecular analyses of infected tissues confirmed that the causative parasite was Pleistophora hyphessobryconis. Compared to P. hyphessobryconis observed in other hosts, those infecting tiger barb demonstrated differences in ultrastructure that may be related to host adaptation. Phylogenetic analysis revealed that classifications based on different methods of analysis (molecular, morphologic, or developmental) do not always coincide, and suggesting that the genetic relationships between Pleistophora and Ovipleistophora may need to be redefined. Transparent mutants of tiger barb can be artificially infected by P. hyphessobryconis, and the dynamic process and spatial distribution of P. hyphessobryconis infection can be observed in real time. These transparent fish mutants are a valuable model to study microsporidial infection in vivo. PMID- 22773046 TI - A Framework for Hierarchical Perception-Action Learning Utilizing Fuzzy Reasoning. AB - Perception-action (P-A) learning is an approach to cognitive system building that seeks to reduce the complexity associated with conventional environment representation/action-planning approaches. Instead, actions are directly mapped onto the perceptual transitions that they bring about, eliminating the need for intermediate representation and significantly reducing training requirements. We here set out a very general learning framework for cognitive systems in which online learning of the P-A mapping may be conducted within a symbolic processing context, so that complex contextual reasoning can influence the P-A mapping. In utilizing a variational calculus approach to define a suitable objective function, the P-A mapping can be treated as an online learning problem via gradient descent using partial derivatives. Our central theoretical result is to demonstrate top-down modulation of low-level perceptual confidences via the Jacobian of the higher levels of a subsumptive P-A hierarchy. Thus, the separation of the Jacobian as a multiplying factor between levels within the objective function naturally enables the integration of abstract symbolic manipulation in the form of fuzzy deductive logic into the P-A mapping learning. We experimentally demonstrate that the resulting framework achieves significantly better accuracy than using P-A learning without top-down modulation. We also demonstrate that it permits novel forms of context-dependent multilevel P-A mapping, applying the mechanism in the context of an intelligent driver assistance system. PMID- 22773047 TI - Adaptive Neuro-Fuzzy Control of a Spherical Rolling Robot Using Sliding-Mode Control-Theory-Based Online Learning Algorithm. AB - As a model is only an abstraction of the real system, unmodeled dynamics, parameter variations, and disturbances can result in poor performance of a conventional controller based on this model. In such cases, a conventional controller cannot remain well tuned. This paper presents the control of a spherical rolling robot by using an adaptive neuro-fuzzy controller in combination with a sliding-mode control (SMC)-theory-based learning algorithm. The proposed control structure consists of a neuro-fuzzy network and a conventional controller which is used to guarantee the asymptotic stability of the system in a compact space. The parameter updating rules of the neuro-fuzzy system using SMC theory are derived, and the stability of the learning is proven using a Lyapunov function. The simulation results show that the control scheme with the proposed SMC-theory-based learning algorithm is able to not only eliminate the steady-state error but also improve the transient response performance of the spherical rolling robot without knowing its dynamic equations. PMID- 22773048 TI - M-Isomap: Orthogonal Constrained Marginal Isomap for Nonlinear Dimensionality Reduction. AB - Isomap is a well-known nonlinear dimensionality reduction (DR) method, aiming at preserving geodesic distances of all similarity pairs for delivering highly nonlinear manifolds. Isomap is efficient in visualizing synthetic data sets, but it usually delivers unsatisfactory results in benchmark cases. This paper incorporates the pairwise constraints into Isomap and proposes a marginal Isomap (M-Isomap) for manifold learning. The pairwise Cannot-Link and Must-Link constraints are used to specify the types of neighborhoods. M-Isomap computes the shortest path distances over constrained neighborhood graphs and guides the nonlinear DR through separating the interclass neighbors. As a result, large margins between both interand intraclass clusters are delivered and enhanced compactness of intracluster points is achieved at the same time. The validity of M-Isomap is examined by extensive simulations over synthetic, University of California, Irvine, and benchmark real Olivetti Research Library, YALE, and CMU Pose, Illumination, and Expression databases. The data visualization and clustering power of M-Isomap are compared with those of six related DR methods. The visualization results show that M-Isomap is able to deliver more separate clusters. Clustering evaluations also demonstrate that M-Isomap delivers comparable or even better results than some state-of-the-art DR algorithms. PMID- 22773049 TI - Co.Vi.Wo.: Color Visual Words Based on Non-Predefined Size Codebooks. AB - Due to the rapid development of information technology and the continuously increasing number of available multimedia data, the task of retrieving information based on visual content has become a popular subject of scientific interest. Recent approaches adopt the bag-of-visual-words (BOVW) model to retrieve images in a semantic way. BOVW has shown remarkable performance in content-based image retrieval tasks, exhibiting better retrieval effectiveness over global and local feature (LF) representations. The performance of the BOVW approach depends strongly, however, on predicting the ideal codebook size, a difficult and database-dependent task. The contribution of this paper is threefold. First, it presents a new technique that uses a self-growing and self organized neural gas network to calculate the most appropriate size of a codebook for a given database. Second, it proposes a new soft-weighting technique, whereby each LF is classified into only one visual word (VW) with a degree of participation. Third, by combining the information derived from the method that automatically detects the number of VWs, the soft-weighting method, and a color information extraction method from the literature, it shapes a new descriptor, called color VWs. Experimental results on two well-known benchmarking databases demonstrate that the proposed descriptor outperforms 15 contemporary descriptors and methods from the literature, in terms of both precision at K and its ability to retrieve the entire ground truth. PMID- 22773050 TI - Children's mental-health language access laws: state factors influence policy adoption. AB - Despite federal legislation to equalize healthcare for children with limited English language proficiency, some state healthcare agencies and programs fall short in providing children's linguistic services for mental healthcare. While some states have been aggressive in passing cultural and linguistic laws aimed at providing protection for children, other states have not, limiting children of all ages to potential substandard care. This research uses state-level data and multivariate regression analysis to explore why some states are adopting these laws, whereas others are not. We find two dissimilar forces with unrelated goals must work in tandem to bring about policy change-the desire of civil rights and liberty groups to ensure equality in the delivery of healthcare services, and the desire of state legislature to reduce healthcare costs. PMID- 22773051 TI - Self-referential and anxiety-relevant information processing in subclinical social anxiety: an fMRI study. AB - The fear of negative evaluation is one of the hallmark features of social anxiety. Behavioral evidence thus far largely supports cognitive models which postulate that information processing biases in the face of socially relevant information are a key factor underlying this widespread phobia. So far only one neuroimaging study has explicitly focused on the fear of negative evaluation in social anxiety where the brain responses of social phobics were compared to healthy participants during the processing of self-referential relative to other referential criticism, praise or neutral information. Only self-referential criticism led to stronger activations in emotion-relevant regions of the brain, such as the amygdala and medial prefrontal cortices (mPFC), in the social phobics. The objective of the current study was to determine whether these findings could be extended to subclinical social anxiety. In doing so, the specificity of this self-referential bias was also examined by including both social and non-social (physical illness-related) threat information as well as a highly health anxious control group in the experimental paradigm. The fMRI findings indicated that the processing of emotional stimuli was accompanied by activations in the amygdala and the ventral mPFC, while self-referential processing was associated with activity in regions such as the mPFC, posterior cingulate and temporal poles. Despite the validation of the paradigm, the results revealed that the previously reported behavioral and brain biases associated with social phobia could not be unequivocally extended to subclinical social anxiety. The divergence between the findings is explored in detail with reference to paradigm differences and conceptual issues. PMID- 22773054 TI - Advanced supramolecular polymers constructed by orthogonal self-assembly. AB - Large aggregates, constructed by linking together monomer building blocks via non covalent interactions with polymer properties, are regarded as supramolecular polymers. Many kinds of non-covalent interactions, such as metal-ligand coordination, hydrogen bonding, pi-pi stacking, ionic interaction, and host-guest interaction etc., can be involved in the binding interactions of monomer building blocks, as well as in the modification of the side chain for the construction of variable supramolecular polymers. In this tutorial review, we summarized the reported supramolecular polymers fully- or partially-created from the combination of multiple non-covalent binding interactions, mainly of two kinds, in the orthogonal way. PMID- 22773055 TI - The highly enantioselective addition of indoles and pyrroles to isatins-derived N Boc ketimines catalyzed by chiral phosphoric acids. AB - The first asymmetric aza-Friedel-Crafts reaction of indoles and pyrroles with isatin-derived N-Boc ketimines catalyzed by chiral phosphoric acids is reported. In general, derivatives of substituted 3-amino-2-oxindoles were obtained with excellent enantioselectivities and high yields. PMID- 22773056 TI - RAF265, a dual BRAF and VEGFR2 inhibitor, prevents osteoclast formation and resorption. Therapeutic implications. AB - INTRODUCTION: The RAS/RAF/MEK/ERK signaling pathway plays an important role in osteoclast (OC) differentiation and survival mediated by macrophage-colony stimulating factor (M-CSF). Also, vascular endothelial growth factor (VEGF) may greatly influence OC formation and resorption through VEGFR1 and VEGFR2. RAF265 is a novel, orally bioavailable dual inhibitor of RAF kinase and VEGFR2. METHODS: Effect of RAF265 on osteoclastogenesis from peripheral blood mononuclear cells (PBMCs) and OC resorption on calcium-coated wells was assessed by appropriate in vitro assays. Immunoblotting, real-time RT-PCR and flow cytometry were used to evaluate RAF265 mechanism of action. RESULTS: RAF265 significantly impaired in vitro differentiation of PBMCs to OCs induced by receptor activator of NF-kB ligand (RANKL) and M-CSF (IC(50) ? 160 nM). In parallel, RAF265 exerted a potent inhibition of OC resorptive capacity (IC(50) ? 20 nM). RAF265 treatment led to ERK inhibition and diminished expression of c-fos and NFATc1 (nuclear factor of activated T cells, calcineurin-dependent 1), which would likely account for inhibition of osteoclastogenesis. The reduced gene expression of aVb3 integrin, CCR1, cathepsin K, carbonic anhydrase II, matrix metalloproteinase 9, urokinase and tissue-type plasminogen activators, vacuolar H(+)-ATPase subunit (ATP6V1A) and Rab7 GTPase would probably mediate RAF265 hindered resorption. RAF265 inhibitory effect on VEGFR2 (noticeable at 10-50 nM) was also found to be implicated in the potent inhibition of this agent on OC function. CONCLUSIONS: We have found a new therapeutic application for RAF265 as an inhibitory agent of osteoclastogenesis and OC function, which might be useful for the treatment of skeletal disorders associated with increased bone resorption. PMID- 22773057 TI - Focal therapy in the management of small renal masses. AB - PURPOSE OF REVIEW: Focal therapy has gained attention in the treatment of small renal masses. However its use is encased by scarce data on long-term outcomes and low evidence regarding perioperative complications. Our purpose is to review the emerging data in the past 18 months. RECENT FINDINGS: Population US-based studies show steady increase in the use of thermal ablation. Clinical series and comprehensive reviews support safety and mid/long-term efficacy. Comparative studies and meta-analysis outlined oncological inferiority against partial nephrectomy in local tumor control. There are profound demographic and tumor differences between patients treated by one or another. Complication rate is lower after ablation but the lack of standard reporting weakens conclusions on this point. Generalizable cost-benefit studies are yet missed. Clinical and basic research aims to diminish radiological associated burden, improving lesion targeting and developing new energy-based technologies. SUMMARY: Data confirm acceptable outcomes of focal therapy in the small renal masses treatment.Although these are inferior in terms of local control compared with partial nephrectomy, patients and tumor characteristics differ between treatments.Current data remain of low evidence but for some meta-analysis. Preliminary reports suggest the possibility to decrease radiation burden and bipolar radiofrequency and photodynamic therapy as focus of future interest. PMID- 22773058 TI - Long-term effect of urethral dilatation and internal urethrotomy for urethral strictures. AB - PURPOSE OF REVIEW: Urethral dilatation and direct visual internal urethrotomy (DVIU) are widely used minimally invasive options to manage men with urethral strictures. Advances in open urethroplasty with better long-term cure rates have fuelled the continuing debate as to which treatment is best for primary and recurrent urethral strictures. We reviewed recent literature to identify contemporary practice of urethral dilatation and DVIU and the long-term outcome of these procedures. RECENT FINDINGS: Systematic literature search for the period January 2010 to December 2011 showed that urethral dilatation and DVIU remain frequently used treatment options as confirmed by surveys of urologists in the USA and the Netherlands. Multiple reports of laser DVIU confirm the safety of this approach but long-term data were lacking. Stricture free rates from urethra dilatation and DVIU vary from 10 to 90% at 12 months, although adjunctive intermittent self-dilatation can reduce time to recurrence. Although quality-of life benefit appears good in the short term, repeated procedures may harm sexual function in the long-term. SUMMARY: Urethral dilatation and DVIU remain widely used in urethral stricture management but high-level comparative evidence of benefit and harms against urethroplasty in the short and long-term is still lacking. PMID- 22773059 TI - Robotics and gaming to improve ankle strength, motor control, and function in children with cerebral palsy--a case study series. AB - The objective of this study was to investigate the feasibility of game-based robotic training of the ankle in children with cerebral palsy (CP). The design was a case study, 12 weeks intervention, with no follow-up. The setting was a university research laboratory. The participants were a referred sample of three children with cerebral palsy, age 7-12, all male. All completed the intervention. Participants trained on the Rutgers Ankle CP system for 36 rehabilitation sessions (12 weeks, three times/week), playing two custom virtual reality games. The games were played while participants were seated, and trained one ankle at-a time for strength, motor control, and coordination. The primary study outcome measures were for impairment (DF/PF torques, DF initial contact angle and gait speed), function (GMFM), and quality of life (Peds QL). Secondary outcome measures relate to game performance (game scores as reflective of ankle motor control and endurance). Gait function improved substantially in ankle kinematics, speed and endurance. Overall function (GMFM) indicated improvements that were typical of other ankle strength training programs. Quality of life increased beyond what would be considered a minimal clinical important difference. Game performance improved in both games during the intervention. This feasibility study supports the assumption that game-based robotic training of the ankle benefits gait in children with CP. Game technology is appropriate for the age group and was well accepted by the participants. Additional studies are needed however, to quantify the level of benefit and compare the approach presented here to traditional methods of therapy. PMID- 22773060 TI - Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. AB - BACKGROUND AND AIMS: Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). METHODS: A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature. RESULTS: A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented. CONCLUSIONS: These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and monitoring of the disease course, while acknowledging that each patient is unique. PMID- 22773061 TI - Asymptomatic massive hepatomegaly and steatosis in a toddler: a diagnostic challenge. PMID- 22773062 TI - Endoscopic and histological gastric lesions in children with celiac disease: mucosal involvement is not only confined to the duodenum. AB - OBJECTIVES: Lymphocytic gastritis (LG) has been reported in patients with celiac disease (CD). The aim of the present study was to evaluate gastric mucosa involvement in celiac children and gastroenterological controls (GC). METHODS: In a retrospective study on 226 patients with CD (82 M; median age: 5.7 years) at diagnosis and 154 GC (66 M; median age: 7.4 years), the evaluation of gastric and duodenal mucosa was performed. CD was diagnosed according to the North America Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria. Gastric lesions were classified according to Updated Sydney System. Anti-gastric parietal cell antibodies (GPCA) were assayed by enzyme-linked immunosorbent assay. RESULTS: A total of 21.2% and 7% of patients with CD showed chronic superficial gastritis (CSG) and LG, respectively. Helicobacter pylori (Hp) infection was found in 6 (2.7%) children with CD (66.7% had CSG, 16.7% LG, and 16.7% interstitial gastritis). CSG was present in 21.4% of controls. No control subject showed LG. Hp infection was found in 24 (15.6%) children with GC (91.7% had CSG). Among patients with CSG, Hp infection was more frequent in controls than in celiac children (P < 0.0001). Ten of 90 patients with CD and 1 of 29 controls were positive for GPCA. CONCLUSIONS: Gastritis is a common finding in children with CD and adolescents. In celiac subjects, CSG is the most frequently detected. Our data suggest the hypothesis that LG may be related to a longer exposure to gluten. The presence of GPCA may suggest the presence of an underlying autoimmune process. PMID- 22773063 TI - SPAG5 mRNA is over-expressed in peripheral blood leukocytes of patients with Down's syndrome and cryptorchidism. AB - Men with Down's syndrome (DS) have an increased risk of cryptorchidism, but the mechanisms causing its onset are not clear. Cryptorchidism causes a primary testiculopathy responsible for infertility. SPAG5 mRNA is predominantly expressed in testis in pachytene spermatocytes. This observation prompted us to evaluate the expression of SPAG5 gene in five DS men with cryptorchidism and five normal healthy men (controls) by quantitative real-time PCR in peripheral blood leukocytes. We found that SPAG5 is over expressed in the five men with DS and cryptorchidism compared with five age- and sex-matched normal controls. This finding suggests that the increased expression of this gene may play a pathogenic role durin testicular development in subjects with DS and cryptorchidism. PMID- 22773064 TI - Digital planning of high tibial osteotomy. Interrater reliability by using two different software. AB - PURPOSE: The purpose of the study was to determine the interrater reliability as well as the correlation of mediCAD((r)) and PreOPlan((r)) in deformity analysis and digital planning of osteotomies. METHODS: Digital radiographs were obtained from 81 patients planned to undergo an open wedge high tibial osteotomy. The JPEG files of the radiographs were imported to landmark-based software. Deformity analysis and planning of correction were performed by 1 experienced and 2 unexperienced observers. Osteotomy planning was aimed at correction to the predefined mechanical tibiofemoral angle of 3 degrees valgus leg alignment. The interrater reliability of measurements was assessed using intraclass correlation coefficients (ICCs) and the confidence interval. RESULTS: The ICC of PreOPlan((r)) was from 0.841 (mechanical lateral distal femur angle) to 0.993 (wedge-angle) and from 0.896 (joint line convergence angle) to 0.995 (mechanical tibiofemoral angle) of mediCAD((r)). The ICC of height of wedge-base was 0.979 with PreOPlan((r)) and 0.969 with mediCAD((r)). Comparing PreOPlan((r)) and mediCAD((r)), the ICC of the height of wedge-base of the observers was 0.966, 0.956 and 0.969, respectively. CONCLUSIONS: The results show a high interrater reliability of digital planning software. Experience of the observer had no influence on results. Furthermore, a high interrater reliability and correlation of digital planning specific parameters was found. Surgeons need to master limb geometry measurements and osteotomy planning on digital radiographs as digital planning reports are used for intercolleagual correspondence, teaching purposes and as medicolegal documents. The digital planning software tested agrees with the actual demands and could be recommended for deformity analysis and planning of osteotomies. LEVEL OF EVIDENCE: Diagnostic studies, Level I. PMID- 22773065 TI - Hip- and knee-strength assessments using a hand-held dynamometer with external belt-fixation are inter-tester reliable. AB - PURPOSE: In football, ice-hockey, and track and field, injuries have been predicted, and hip- and knee-strength deficits quantified using hand-held dynamometry (HHD). However, systematic bias exists when testers of different sex and strength perform the measurements. Belt-fixation of the dynamometer may resolve this. The aim of the present study was therefore to examine the inter tester reliability concerning strength assessments of isometric hip abduction, adduction, flexion, extension and knee-flexion strength, using HHD with external belt-fixation. METHODS: Twenty-one healthy athletes (6 women), 30 (8.6) (mean (SD)) years of age, were included. Two physiotherapy students (1 female and 1 male) performed all the measurements after careful instruction and procedure training. Isometric hip abduction, adduction, flexion, extension, and knee flexion strength were tested. The tester-order and hip-action order were randomised. RESULTS: No systematic between-tester differences (bias) were observed for any of the hip or knee actions. The intra-class correlation coefficients (ICC 2.1) ranged from 0.76 to 0.95. Furthermore, standard errors of measurement in per cent (SEM %) ranged from 5 to 11 %, and minimal detectable change in per cent (MDC %) from 14 to 29 % for the different hip and knee actions. CONCLUSION: The present study shows that isometric hip- and knee strength measurements have acceptable inter-tester reliability at the group level, when testing strong individuals, using HHD with belt-fixation. This procedure is therefore perfectly suited for the evaluation and monitoring of strong athletes with hip, groin and hamstring injuries, some of the most common and troublesome injuries in sports. LEVELS OF EVIDENCE: Diagnostic, Level III. PMID- 22773066 TI - Acute muscle strain injuries: a proposed new classification system. AB - PURPOSE: To better define and classify acute muscle strain injuries. METHODS: Historically, acute muscle strains have been classified as grade I, II and III. This system does not accurately reflect the anatomy of the injury and has not been shown to reliably predict prognosis and time for return to sport. RESULTS: We describe an imaging (magnetic resonance or ultrasound) nomenclature, which considers the anatomical site, pattern and severity of the lesion in the acute stage. By site of injury, we define muscular injuries as proximal, middle and distal. Anatomically, based on the various muscular structures involved, we distinguish intramuscular, myofascial, myofascial/perifascial and musculotendinous injuries. CONCLUSIONS: This classification system must be applied to a variety of muscle architectures and locations to determine its utility; additional studies are therefore needed prior to its general acceptance. LEVEL OF EVIDENCE: V. PMID- 22773067 TI - Biomechanics of high tibial osteotomy. AB - PURPOSE: This paper is a review of the biomechanical principles that support limb realignment surgery via osteotomy around the knee, principally high (proximal) tibial osteotomy. METHODS: The basic biomechanical principles have been described, and the related literature examined for evidence to support the recommendations made. RESULTS: The forces on the knee when walking are shown to lead to most of the load acting through the medial compartment, the most frequent site of degeneration of the knee, due to the adduction moment that acts during the weight-acceptance phase. Realignment of the limb to move the mechanical axis to a desired point within the knee is described, and the resulting joint contact pressures in the medial and lateral compartments are shown to be higher in the less-congruent lateral articulation when the load passes through the centre of the knee. At the same time, there can be changes of the posterior slope of the tibial plateau, and a slope of ten degrees can induce a shearing force, which stretches the ACL, of 0.5 body weight when the knee force is 3 times body weight. The options regarding tibial or femoral or even double osteotomies are discussed in relation to medial-lateral slope of the joint line. Secondary effects such as alteration of collateral ligament tension or of the height of the patella are described. CONCLUSION: Critical review of the publications supporting osteotomy surgery suggests that many of the accepted 'rules' have little scientific evidence to show that they represent the best practise for long-term preservation of the joint. PMID- 22773068 TI - The Adaptation for Conservation Targets (ACT) framework: a tool for incorporating climate change into natural resource management. AB - As natural resource management agencies and conservation organizations seek guidance on responding to climate change, myriad potential actions and strategies have been proposed for increasing the long-term viability of some attributes of natural systems. Managers need practical tools for selecting among these actions and strategies to develop a tailored management approach for specific targets at a given location. We developed and present one such tool, the participatory Adaptation for Conservation Targets (ACT) framework, which considers the effects of climate change in the development of management actions for particular species, ecosystems and ecological functions. Our framework is based on the premise that effective adaptation of management to climate change can rely on local knowledge of an ecosystem and does not necessarily require detailed projections of climate change or its effects. We illustrate the ACT framework by applying it to an ecological function in the Greater Yellowstone Ecosystem (Montana, Wyoming, and Idaho, USA)--water flows in the upper Yellowstone River. We suggest that the ACT framework is a practical tool for initiating adaptation planning, and for generating and communicating specific management interventions given an increasingly altered, yet uncertain, climate. PMID- 22773069 TI - Spatial variability in cost and success of revegetation in a Wyoming big sagebrush community. AB - The ecological integrity of the Wyoming big sagebrush (Artemisia tridentata Nutt. ssp. wyomingensis Beetle and A. Young) alliance is being severely interrupted by post-fire invasion of non-native annual grasses. To curtail this invasion, successful post-fire revegetation of perennial grasses is required. Environmental factors impacting post-fire restoration success vary across space within the Wyoming big sagebrush alliance; however, most restorative management practices are applied uniformly. Our objectives were to define probability of revegetation success over space using relevant soil-related environmental factors, use this information to model cost of successful revegetation and compare the importance of vegetation competition and soil factors to revegetation success. We studied a burned Wyoming big sagebrush landscape in southeast Oregon that was reseeded with perennial grasses. We collected soil and vegetation data at plots spaced at 30 m intervals along a 1.5 km transect in the first two years post-burn. Plots were classified as successful (>5 seedlings/m(2)) or unsuccessful based on density of seeded species. Using logistic regression we found that abundance of competing vegetation correctly predicted revegetation success on 51 % of plots, and soil related variables correctly predicted revegetation performance on 82.4 % of plots. Revegetation estimates varied from $167.06 to $43,033.94/ha across the 1.5 km transect based on probability of success, but were more homogenous at larger scales. Our experimental protocol provides managers with a technique to identify important environmental drivers of restoration success and this process will be of value for spatially allocating logistical and capital expenditures in a variable restoration environment. PMID- 22773070 TI - Analysis of pathogen co-occurrence in host-seeking adult hard ticks from Serbia. AB - Past studies in Serbia have reported concurrent infections of Ixodes ricinus ticks with Borrelia burgdorferi sensu lato genospecies, Anaplasma phagocytophilum and Francisella tularensis. As a step forward, this investigation included a broader range of microorganisms and five most common and abundant tick species in Serbia. Five tick species were identified (Dermacentor marginatus, D. reticulatus, Haemaphysalis punctata, H. concinna and I. ricinus) and analyzed for the presence of seven pathogens. Anaplasma ovis, A. phagocytophilum, Babesia canis, B. burgdorferi s.l., Coxiella burnetii, Rickettsia helvetica and R. monacensis were detected. Sequencing of samples positive for F. tularensis revealed the presence of Francisella-like endosymbionts. No Bartonella spp. DNA was amplified. Concurrent infections were present in three tick species (D. reticulatus, H. concinna and I. ricinus). The rate of co-infections was highest in I. ricinus (20/27), while this tick species harbored the broadest range of co infection combinations, with dual, triple and a quadruple infection(s) being detected. PMID- 22773071 TI - Gene silencing in tick cell lines using small interfering or long double-stranded RNA. AB - Gene silencing by RNA interference (RNAi) is an important research tool in many areas of biology. To effectively harness the power of this technique in order to explore tick functional genomics and tick-microorganism interactions, optimised parameters for RNAi-mediated gene silencing in tick cells need to be established. Ten cell lines from four economically important ixodid tick genera (Amblyomma, Hyalomma, Ixodes and Rhipicephalus including the sub-species Boophilus) were used to examine key parameters including small interfering RNA (siRNA), double stranded RNA (dsRNA), transfection reagent and incubation time for silencing virus reporter and endogenous tick genes. Transfection reagents were essential for the uptake of siRNA whereas long dsRNA alone was taken up by most tick cell lines. Significant virus reporter protein knockdown was achieved using either siRNA or dsRNA in all the cell lines tested. Optimum conditions varied according to the cell line. Consistency between replicates and duration of incubation with dsRNA were addressed for two Ixodes scapularis cell lines; IDE8 supported more consistent and effective silencing of the endogenous gene subolesin than ISE6, and highly significant knockdown of the endogenous gene 2I1F6 in IDE8 cells was achieved within 48 h incubation with dsRNA. In summary, this study shows that gene silencing by RNAi in tick cell lines is generally more efficient with dsRNA than with siRNA but results vary between cell lines and optimal parameters need to be determined for each experimental system. PMID- 22773072 TI - Racial and ethnic differences in the immigrant paradox in substance use. AB - Using data from the National Longitudinal Studies of Adolescent Health, the present study examines self-reported substance use (cigarettes, tobacco, and marijuana) among youth from different immigration generations to determine the immigrant paradox in substance use for different racial and ethnic groups as well as factors contributing to the relationship between immigration and substance use. Results of data analysis indicate the immigrant paradox in substance use among non-Hispanic Whites, Asians, and Hispanics, but not among non-Hispanic Blacks. The study also shows that factors explaining the immigrant paradox in substance use vary with racial and ethnic groups, but English use at home, friends' cigarette and marijuana use appear to be the most important mediating factors. Findings from the study suggest that effective interventions in youth substance use require an understanding of adaptation patterns in different racial and ethnic groups, so that factors associated with adaptation problems experienced by particular groups will be appropriately addressed. PMID- 22773073 TI - Newcomers health in Brantford and the counties of Brant, Haldimand and Norfolk: perspectives of newcomers and service providers. AB - The Canadian government's plan to support a balanced distribution of immigrants throughout the nation has contributed to newcomers' dispersion to small town communities and rural areas. However, very little work has examined the health experiences of immigrants settling in smaller urban and rural regions. Even less literature exists on the perspectives of service providers working with newcomers in Canada's urban-rural communities. This paper focuses on a part of a larger Community-based study on 'Newcomer Settlement and Integration in Education, Training, Employment, Health and Social Support' in Brantford--a middle-sized urban/rural region in Ontario, Canada--and discusses the findings in the health domain. Data were generated from 212 service providers and 237 newcomers using both qualitative and quantitative research tools. Newcomers identified several barriers in accessing mental and/or physical health services including lack of culturally appropriate services and discrimination. The striking differences between newcomers' and service providers' responses to the survey questionnaires bring to light cultural variations between the newcomers' and the service providers' perceptions of 'health'. The findings reinforce the need for including newcomers in developing more inclusive and culturally-appropriate health services and programs. PMID- 22773074 TI - Impact of smoking status on outcome in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. AB - There are some data showing lower mortality of smokers comparing to non-smokers in patients with ST-segment elevation myocardial infarction (STEMI) when treated with thrombolysis or without reperfusion therapy. However, the role of smoking status is less established in patients with STEMI undergoing mechanical reperfusion. We evaluate the influence of smoking on outcome in patients with STEMI treated with primary percutaneous coronary intervention (PCI). A total of 1,086 patients enrolled into EUROTRANSFER Registry were included into present analysis. Patients were divided according to smoking status during STEMI presentation into those who were current smokers (391 patients, 36 %) and non smokers (695 patients, 64 %). Current smokers were younger and more often men and less frequently had high-risk features as previous myocardial infarction, history of chronic renal failure, previous PCI, diabetes mellitus, anterior wall STEMI, and multivessel disease. Unadjusted mortality at 1 year was lower in current smokers comparing to non-smokers (3.3 vs. 9.5 %; OR 0.33 CI 0.18-0.6; p = 0.0001). However, after adjustment for age and gender by logistic regression, there was no longer significant difference between groups (OR 0.7; CI 0.37-1.36; p = 0.30). In conclusion, current smokers with STEMI treated with primary PCI have lower mortality at 1 year comparing to non-smokers, but this result may be explained by differences in baseline characteristics and not by smoking status itself. Current smokers developed STEMI more than 10 years earlier than non smokers with similar age and sex-adjusted risk of death at 1 year. These results emphasize the role of efforts to encourage smoking cessation as prevention of myocardial infarction. PMID- 22773075 TI - Warts in a cohort of Danish kidney transplanted patients: impact on quality of life. AB - There are no published clinical studies evaluating the impact of warts on quality of life after transplantation. The aim of this study was to determine the frequency of self-reported skin warts and skin cancer and their impact on quality of life in kidney transplanted patients, as measured with the Dermatology Life Quality Index (DLQI). Of 740 patients with a functioning renal allograft and were free of dialysis who were surveyed, 568 returned the questionnaires. Patients were asked about general health issues, with a focus on transplantation history, cutaneous warts and whether they had ever had cutaneous cancer. A total of 285 (52%) patients replied that they had warts, and these increased with time since last transplantation, with a p-value < 0.0001. A total of 101 patients (18%) reported that they had ever had skin cancer. The median DLQI was 0 for patients not having warts, 1 for patients with warts, and 2 for patients having warts and skin cancer. In conclusion, renal transplant recipients experience increasing numbers of warts and skin cancer over time, and having skin cancer impairs patients' quality of life to a greater degree than warts. PMID- 22773076 TI - Supporting regenerative medicine by integrative dimensionality reduction. AB - OBJECTIVE: The assessment of the developmental potential of stem cells is a crucial step towards their clinical application in regenerative medicine. It has been demonstrated that genome-wide expression profiles can predict the cellular differentiation stage by means of dimensionality reduction methods. Here we show that these techniques can be further strengthened to support decision making with i) a novel strategy for gene selection; ii) methods for combining the evidence from multiple data sets. METHODS: We propose to exploit dimensionality reduction methods for the selection of genes specifically activated in different stages of differentiation. To obtain an integrated predictive model, the expression values of the selected genes from multiple data sets are combined. We investigated distinct approaches that either aggregate data sets or use learning ensembles. RESULTS: We analyzed the performance of the proposed methods on six publicly available data sets. The selection procedure identified a reduced subset of genes whose expression values gave rise to an accurate stage prediction. The assessment of predictive accuracy demonstrated a high quality of predictions for most of the data integration methods presented. CONCLUSION: The experimental results highlighted the main potentials of proposed approaches. These include the ability to predict the true staging by combining multiple training data sets when this could not be inferred from a single data source, and to focus the analysis on a reduced list of genes of similar predictive performance. PMID- 22773077 TI - Intestinal absorption of forsythoside A in in situ single-pass intestinal perfusion and in vitro Caco-2 cell models. AB - AIM: To investigate the mechanisms underlying the intestinal absorption of the major bioactive component forsythoside A (FTA) extracted from Forsythiae fructus. METHODS: An in vitro Caco-2 cell model and a single-pass intestinal perfusion in situ model in SD rats were used. RESULTS: In the in vitro Caco-2 cell model, the mean apparent permeability value (P(app)-value) was 4.15*10(-7) cm/s in the apical-to-basolateral (AP-BL) direction. At the concentrations of 2.6-10.4 MUg/mL, the efflux ratio of FTA in the bi-directional transport experiments was approximately 1.00. After the transport, >96% of the apically loaded FTA was retained on the apical side, while >97% of the basolaterally loaded FTA was retained on the basolateral side. The P(app)-values of FTA were inversely correlated with the transepithelial electrical resistance. The paracellular permeability enhancers sodium caprate and EDTA, the P-gp inhibitor verapamil and the multidrug resistance related protein (MRP) inhibitors cyclosporine and MK571 could concentration-dependently increase the Papp-values, while the uptake (OATP) transporter inhibitors diclofenac sodium and indomethacin could concentration dependently decrease the P(app)-values. The intake transporter SGLT1 inhibitor mannitol did not cause significant change in the P(app)-values. In the in situ intestinal perfusion model, both the absorption rate constant (K(a)) and the effective permeability (P(eff)-values) following perfusion of FTA 2.6, 5.2 and 10.4 MUg/mL via the duodenum, jejunum and ileum had no significant difference, although the values were slightly higher for the duodenum as compared to those in the jejunum and ileum. The low, medium and high concentrations of verapamil caused the largest increase in the P(eff)-values for duodenum, jejunum and ileum, respectively. Sodium caprate, EDTA and cyclosporine resulted in concentration dependent increase in the P(eff)-values. Diclofenac sodium and indomethacin caused concentration-dependent decrease in the Peff-values. Mannitol did not cause significant change in the P(app)-values for the duodenum, jejunum or ileum. CONCLUSION: The results suggest that the intestinal absorption of FTA may occur through passive diffusion, and the predominant absorption site may be in the upper part of small intestine. Paracellular transport route is also involved. P gp, MRPs and OATP may participate in the absorption of FTA in the intestine. The low permeability of FTA contributes to its low oral bioavailability. PMID- 22773078 TI - [Estimation of the execution of the national strategy of leprosy elimination in the "Hauts Bassins" region in Burkina Faso]. AB - BACKGROUND: Burkina Faso achieved the leprosy elimination as a public health problem but this benefit was being lost. So, the National Program for Fighting against Leprosy has defined a strategy to reverse this situation. The aim of this survey was to evaluate the performance of the national program in the execution of this strategy in the region of "Hauts Bassins" (Burkina Faso) from 2005 to 2009. METHOD: The survey was led through the five sanitary districts of the region. It consisted in interview with the mean actors of leprosy control program and the analysis of the data notified on the leprosy cases, in order to estimate the progression of the key indicators of detection and follow-up care for patients having leprosy. RESULTS: During the survey period, 248 cases of leprosy were recorded including 236 new cases and 12 relapses. The prevalence of leprosy was 0.28 per 100 000 inhabitants in 2009. The detection rate decreased from 3.77 per 100 000 in 2005 to 2.75 per 100 000 in 2009. Among the 236 new cases of leprosy, 194 (82.2 %) were multibacillary form (MB). MB patients proportion increased from 69,3 % in 2005 to 91.1 % in 2009. The proportion of children was on average 3.8 %, the one of female cases 38.9 %. Newly diagnosed cases with grade 2 disabilities moved up from 21.4 % in 2005 to 42.2 % in 2009. The completion of cure rate was globally 88.26 %. The losts from follow-up among the patients who started multi-drug therapy were 7.14 %. CONCLUSION: The aim of the leprosy elimination as a public health problem is achieved but some challenges may be taken up, particularly in the organization of leprosy detection by the heath structures. PMID- 22773079 TI - Appraisal of heavy metal concentration in selected vegetables exposed to different degrees of pollution in Agra, India. AB - The accumulation of air-borne heavy metals in edible parts of vegetables in the chosen areas of the city of Agra, India was investigated. Agra, with a population of 1.7 million, is a medium-sized Indian city where leafy green vegetables are received generally from the surrounding areas of about 50 km radius. Vegetables Basella alba (spinch, locally called palak), Trigonella foenumgraecum (fenugreek, locally called methi), and Coriandrum sativum (coriander, locally called dhania) from the various sites of Agra, India were tested for Pb, Cd, Cr, Ni, and Zn by atomic absorption spectroscopy in washed and unwashed vegetable. The results obtained from this analysis revealed higher concentrations of toxic elements in unwashed samples than the washed samples. Among unwashed samples it was found that concentration of heavy metals is more in areas of busy traffic or industry density. The levels of lead in all samples were found above the maximum permissible limit recommended by PFA for metals in vegetables. The study concludes that transportation and storage systems during marketing play a significant role in determining the contamination and deposition of heavy metal on vegetable surfaces specially of the leafy variety. PMID- 22773080 TI - Assessment of anthropogenic influences on surface water quality in urban estuary, northern New Jersey: multivariate approach. AB - Concentrations of selected heavy metals (Cd, Cr, Cu, Pb, Ni, Fe, and Zn), nutrients (NO (3) (-) and NH(3)), fecal coliform colonies, and other multiple physical-chemical parameters were measured seasonally from 12 locations in an urban New Jersey estuary between 1994 and 2008. Stepwise regression, principal component analysis, and cluster analysis were used to group water quality results and sampling locations, as well as to assess these data's relationship to sewage treatment effluents and the distance to the mouth of the river. The BOD(5), NH(3), NO (3) (-) and fecal coliform counts clustered as one group and positively correlated to the distances from treated effluent and the measures of magnitude at the discharge points. Dissolved solids and most metal species scored high along a single principal component axes and were significantly correlated with the proximity to the industrialized area. From these data, one can conclude that the effluent discharge has been a main source of anthropogenic input to the Hackensack River over the past 15 years. Therefore, the greatest improvement to water quality would come from eliminating the few remaining combined sewer overflows and improving the removal of nutrients from treated effluents before they are discharged into the creeks and river. PMID- 22773081 TI - Geochemical evaluation of present-day Tuul River sediments, Ulaanbaatar basin, Mongolia. AB - The Tuul River flows through the Ulaanbaatar basin of Mongolia and is the main source of water for the capital city, Ulaanbaatar. The Tuul catchment can be divided into three parts around Ulaanbaatar (upper, middle, and lower), according to the extent of urbanization. Sixteen surface water and groundwater samples were collected to evaluate present-day water quality and 34 stream sediment samples taken to examine their geochemical composition in relation to provenance and to assess the impact of urban activity on heavy metal accumulation. Groundwater quality in the upper and central water sources was adequate, but high concentrations of NO (3) (-) were found in the lower water source. Heavy metal concentrations in the sediments are evaluated by comparison with average upper continental crust (UCC) values, coupled with ecological risk assessment by reference to sediment quality guidelines (SQG). The results show average abundances of potentially toxic metals such as As, Pb, Zn, Cu, Ni, Cr, and V are higher in the middle part (within the city) than in the upper and lower parts. However, all three parts show depletion in some chalcophile and high field strength elements (Cu, Ni, Cr, Sr, Nb, Zr, Th, Sc) relative to UCC, indicating that the river sediments were derived from a highly felsic crustal source. The assessment using SQG shows As and Cr are present in levels that cause adverse aquatic biological effects. Although concentrations of Pb, Zn, Cu, and Ni are generally below their respective threshold effect levels, in the middle reaches, values increase and border on the probable effect level. This suggests significant anthropogenic contamination in the urban areas, increasing values above a naturally low regional background. PMID- 22773082 TI - Contamination by perfluorinated compounds in water near waste recycling and disposal sites in Vietnam. AB - There are very few reports on the contamination by perfluorinated chemicals (PFCs) in the environment of developing countries, especially regarding their emission from waste recycling and disposal sites. This is the first study on the occurrence of a wide range of PFCs (17 compounds) in ambient water in Vietnam, including samples collected from a municipal dumping site (MD), an e-waste recycling site (ER), a battery recycling site (BR) and a rural control site. The highest PFC concentration was found in a leachate sample from MD (360 ng/L). The PFC concentrations in ER and BR (mean, 57 and 16 ng/L, respectively) were also significantly higher than those detected in the rural control site (mean, 9.4 ng/L), suggesting that municipal solid waste and waste electrical and electronic equipment are potential contamination sources of PFCs in Vietnam. In general, the most abundant PFCs were perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUDA; <1.4-100, <1.2-100, and <0.5-20 ng/L, respectively). Interestingly, there were specific PFC profiles: perfluoroheptanoic acid and perfluorohexanoic acid (88 and 77 ng/L, respectively) were almost as abundant as PFOA in MD leachate (100 ng/L), whereas PFNA was prevalent in ER and BR (mean, 17 and 6.2 ng/L, respectively) and PFUDA was the most abundant in municipal wastewater (mean, 5.6 ng/L), indicating differences in PFC contents in different waste materials. PMID- 22773083 TI - Cytochrome P450 system as potential biomarkers of certain toxicants: comparison between plant and animal models. AB - In present study, we measured the activities of some selected cytochrome P450 isozymes like ethoxyresorufin-o-deethylase (EROD), pentoxyresorufin-o-deethylase (PROD), and N-nitrosodimethylamine demethylase (NDMA-d) treating experimental rats with different environmental toxicants, namely trichloroethylene (TCE), heavy metal mixture, and ethyl alcohol individually or in combination and by exposing the Allium cepa bulbs to increasing concentration of TCE for 48 h. In animal system, NDMA-d activity displayed a remarkable amplification by 4.2-fold in the liver of alcohol ingested rats compared with control animals. TCE intake also resulted in a marked increase of around 3.8-fold and 1.2-fold in rats' NDMA d activity in the liver and kidney, respectively. In onion bulbs, an amazing rise in the activity of test enzymes was recorded in a dose-dependent manner. Among the said enzymes, PROD showed maximum increase up to the extent of 22-fold in comparison with control at 20 ppm of TCE exposure, whereas NDMA-d and EROD showed 11- and 9-fold increase in enzymatic activity, respectively, compared with the control. Based on this study, we conclude and advocate that all the selected isozymes of CYP450 system, viz. PROD, NDMA-d, and EROD can act as potent biomarkers in plant system for assessing the TCE pollution. PMID- 22773084 TI - Systemic and extraintestinal forms of human infection due to non-typhoid salmonellae in Bulgaria, 2005-2010. AB - The purpose of this investigation was to review the clinical cases diagnosed as systemic or extraintestinal salmonellosis between 2005 and 2010 in Bulgaria, to determine the antimicrobial resistance of the causative salmonellae, and to analyze the pulsed field gel electrophoresis (PFGE) profiles of extraintestinal Salmonella Corvallis isolates. Culture, biochemical tests, and serotyping were performed. Resistance to 12 antimicrobial agents was studied with the Bauer-Kirby disk diffusion method. The double-disk synergy method was used for the screening of the presence of extended-spectrum beta-lactamases (ESBLs). PFGE typing and analysis of the dendrogram was performed for the comparative investigation of Salmonella Corvallis isolates. Between 2005 and 2010, 2,227 human non-typhoid Salmonella isolates were investigated at the National Reference Laboratory of Enteric Pathogens, Sofia, Bulgaria. Thirty-three strains (1.48 %) from nine national regions were isolated from patients with systemic and extraintestinal forms of salmonellosis. The serotype distribution was as follows: S. enteritidis (n = 21), S. choleraesuis (diphasic n = 3; monophasic n = 3), S. typhimurium (n = 2), Salmonella Corvallis (n = 2), Salmonella Montevideo (n = 1), and S. javiana (n = 1). Eight patients developed severe forms of infections: sepsis (n = 2), septic shock (n = 1 with fatal outcome), meningitis (n = 3), and acute renal failure (n = 2). Twenty-two percent of isolates were resistant to ampicillin and gentamicin, 17.64 % to tetracycline, 14.28 % to nalidixic acid, and 10 % to chloramphenicol. All isolates were susceptible to ciprofloxacin. One Salmonella Corvallis isolate recovered from a patient with chronic hemolytic anemia produced an ESBL and its PFGE profile demonstrated less than 96 % similarity to fecal and wound Salmonella Corvallis with susceptible phenotypes. S. enteritidis was the most common cause of systemic and extraintestinal forms of human salmonellosis in Bulgaria. Resistance to ampicillin and gentamicin were the predominant profiles, although one Salmonella Corvallis isolate produced an ESBL. The ESBL-producing Salmonella Corvallis isolate clustered separately from the susceptible Salmonella Corvallis isolates. PMID- 22773085 TI - Dumping symptoms and incidence of hypoglycaemia after provocation test at 6 and 12 months after laparoscopic sleeve gastrectomy. AB - BACKGROUND: A previous study has demonstrated that symptoms suggestive of dumping syndrome appear after a provocation test early after laparoscopic sleeve gastrectomy (LSG) in 45 % of patients, and these are mainly related to early dumping. The aim of this study is to evaluate the evolution of dumping symptoms during the first postoperative year. METHODS: Twenty-five non-diabetic morbidly obese patients (6 male, 19 female) were evaluated with an oral glucose tolerance test (OGTT) preoperatively, at 6 weeks and at 6 months postoperatively. In addition, 12 of them repeated the OGTT at 12 months after LSG. Sigstad score was used to separate dumpers from non-dumpers and Arts' questionnaire to differentiate between early and late dumping. Insulin and glucose levels were also measured. RESULTS: Sigstad score remained significantly elevated at 6 and 12 months postoperatively compared to preoperative values. Symptoms suggestive of dumping syndrome were recorded in 40 % of patients at 6 months and in 33 % at 12 months postoperatively. Arts' questionnaire demonstrated that early dumping score remained higher compared to baseline at 6 and 12 months postoperatively. Late dumping scores increased gradually during the time and that difference was statistically significant at 12 months after LSG. Hypoglycaemia occurred at 33 % of patients both at 6 and 12 months postoperatively. CONCLUSIONS: Symptoms suggestive of dumping syndrome after provocation still exist at 6 and 12 months in a significant proportion of patients after LSG and include both early and late dumping. These findings are consistent with the high incidence of hypoglycaemia after OGTT at 6 and 12 months after LSG. PMID- 22773086 TI - Natural epigenetic variation in the female great roundleaf bat (Hipposideros armiger) populations. AB - Epigenetic modifications are considered to have an important role in evolution. DNA methylation is one of the best studied epigenetic mechanisms and methylation variability is crucial for promoting phenotypic diversification of organisms in response to environmental variation. A critical first step in the assessment of the potential role of epigenetic variation in evolution is the identification of DNA methylation polymorphisms and their relationship with genetic variations in natural populations. However, empirical data is scant in animals, and particularly so in wild mammals. Bats are considered as bioindicators because of their sensitivity to environmental perturbations and they may present an opportunity to explore epigenetic variance in wild mammalian populations. Our study is the first to explore these questions in the female great roundleaf bat (Hipposideros armiger) populations using the methylation-sensitive amplified polymorphism (MSAP) technique. We obtained 868 MSAP sites using 18 primer combinations and found (1) a low genomic methylation level (21.3 % on average), but extensive DNA methylation polymorphism (90.2 %) at 5'-CCGG-3' sites; (2) epigenetic variation that is structured into distinct between- (29.8 %) and within- (71.2 %) population components, as does genetic variation; and (3) a significant correlation between epigenetic and genetic variations (P < 0.05). These results may also apply to other wild mammalian populations. The possible causes for the correlation between epigenetic and genetic variations are discussed. PMID- 22773087 TI - Nonlinear fluorescence response driven by ATP-induced self-assembly of guanidinium-tethered tetraphenylethene. AB - Nonlinear fluorescence response, which is particularly important to attain the high signal-to-background ratio, was realized by the aggregation-induced fluorescence increase of guanidinium-tethered tetraphenylethene with ATP. PMID- 22773089 TI - Clinical features of reticular pseudodrusen according to the fundus distribution. AB - BACKGROUND: To evaluate the morphological features and prevalence of accompanying late age-related macular degeneration (AMD) according to the fundus distribution of reticular pseudodrusen (RPD). METHODS: According to the involved area in the fundus, the distribution of RPD was classified as localised, intermediate, or diffuse type. Morphology of RPD was classified as discrete, branching, or confluent pattern. The presence of late AMD was evaluated. RESULTS: 233 eyes of 121 patients with RPD were included. The distribution of RPD was localised, intermediate and diffuse type in 30.9%, 40.3% and 28.8% of eyes, respectively. The discrete, branching and confluent morphological patterns were found in 45.8%, 44.8% and 9.7% of the localised type, and in 0%, 13.8% and 86.2% of the intermediate type, respectively. In contrast, the diffuse type showed only the confluent morphological pattern. The prevalence of accompanying late AMD was 13.9%, 13.8% and 56.7% in the localised, intermediate and diffuse type, respectively, and it was significantly higher in the diffuse type (p<0.05). CONCLUSION: RPD with diffuse distribution showed a confluent morphological pattern and a high prevalence of late AMD. RPD can be classified by the fundus distribution for the assessment of visual prognosis. PMID- 22773088 TI - Acupuncture suppresses kainic acid-induced neuronal death and inflammatory events in mouse hippocampus. AB - The administration of kainic acid (KA) causes seizures and produces neurodegeneration in hippocampal CA3 pyramidal cells. The present study investigated a possible role of acupuncture in reducing hippocampal cell death and inflammatory events, using a mouse model of kainic acid-induced epilepsy. Male C57BL/6 mice received acupuncture treatments at acupoint HT8 or in the tail area bilaterally once a day for 2 days and again immediately after an intraperitoneal injection of KA (30 mg/kg). HT8 is located on the palmar surface of the forelimbs, between the fourth and fifth metacarpal bones. Twenty-four hours after the KA injection, neuronal cell survival, the activations of microglia and astrocytes, and mRNA expression of two proinflammatory cytokines, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), were measured in the hippocampus. Acupuncture stimulation at HT8, but not in the tail area, significantly reduced the KA-induced seizure, neuron death, microglial and astrocyte activations, and IL-1beta mRNA expression in the hippocampus. The acupuncture stimulation also decreased the mRNA expression of TNF-alpha, but it was not significant. These results indicate that acupuncture at HT8 can inhibit hippocampal cell death and suppress KA-induced inflammatory events, suggesting a possible role for acupuncture in the treatment of epilepsy. PMID- 22773091 TI - Clinical characteristics of newly diagnosed primary, pigmentary and pseudoexfoliative open-angle glaucoma in the Collaborative Initial Glaucoma Treatment Study. AB - BACKGROUND/AIMS: Three types of open-angle glaucoma (OAG)--primary, pigmentary and pseudoexfoliative--are frequently encountered. The aim of this study was to compare demographic, ocular and systemic medical information collected on people with these three OAG types at diagnosis, and determine if the OAG type affected the prognosis. METHODS: Information on 607 participants of the Collaborative Initial Glaucoma Treatment Study was accessed. Descriptive statistics characterised their demographic, ocular and medical status at diagnosis. Comparisons were made using analysis of variance and chi(2) or Fisher's exact tests. Multinomial, mixed and logistic regression analyses were also performed. RESULTS: Relative to people with primary OAG, those with pigmentary OAG were younger, more likely to be white, less likely to have a family history of glaucoma, and were more myopic. Those with pseudoexfoliative OAG were older, more likely to be white, more likely to be women, less likely to have bilateral disease, and presented with higher intraocular pressure (IOP) and better visual acuity. The type of glaucoma was not associated with IOP or visual field progression during follow-up. CONCLUSION: Characteristics of newly diagnosed enrollees differed by the type of OAG. While some of these differences relate to the pathogenesis of OAG type, other differences are noteworthy for further evaluation within population-based samples of subjects with newly diagnosed OAG. PMID- 22773092 TI - A minimally invasive microchip for transdermal injection/sampling applications. AB - The design, fabrication, and characterization of a minimally invasive silicon microchip for transdermal injection/sampling applications are reported and discussed. The microchip exploits an array of silicon-dioxide hollow microneedles with density of one million needles cm(-2) and lateral size of a few micrometers, protruding from the front-side chip surface for one hundred micrometers, to inject/draw fluids into/from the skin. The microneedles are in connection with independent reservoirs grooved on the back-side of the chip. Insertion experiments of the microchip in skin-like polymers (agarose hydrogels with concentrations of 2% and 4% wt) demonstrate that the microneedles successfully withstand penetration without breaking, despite their high density and small size, according to theoretical predictions. Operation of the microchip with different liquids of biomedical interest (deionized water, NaCl solution, and d glucose solution) at different differential pressures, in the range 10-100 kPa, highlights that the flow-rate through the microneedles is linearly dependent on the pressure-drop, despite the small section area (about 13 MUm(2)) of the microneedle bore, and can be finely controlled from a few ml min(-1) up to tens of ml min(-1). Evaporation (at room temperature) and acceleration (up to 80 g) losses through the microneedles are also investigated to quantify the ability of the chip in storing liquids (drug to be delivered or collected fluid) in the reservoir, and result to be of the order of 70 nl min(-1) and 1300 nl min(-1), respectively, at atmospheric pressure and room temperature. PMID- 22773094 TI - Human rights from the grassroots up: Vermont's campaign for universal health care. AB - In 2008, the Vermont Workers' Center launched the "Healthcare Is a Human Right Campaign," a grassroots campaign to secure the creation of a universal health care system in Vermont. Campaign organizers used a human rights framework to mobilize thousands of voters in support of universal health care. In response to this extraordinary grassroots effort, the state legislature passed health care legislation that incorporates human rights principles into Vermont law and provides a framework for universal health care. The United States has often lagged behind other nations in recognizing economic, social, and cultural (ESC) rights, including the right to health. Nonetheless, activists have begun to incorporate ESC rights into domestic advocacy campaigns, and state and local governments are beginning to respond where the federal government has not. Vermont serves as a powerful example of how a human rights framework can inform health care policy and inspire grassroots campaigns in the United States. This three-part article documents the Vermont Workers' Center campaign and discusses the impact that human rights activity at the grassroots level may have on attitudes towards ESC rights in the United States. The first part describes the Vermont health care crisis and explains why the center adopted international human rights principles for their campaign. The article then goes on to discuss the three-year campaign and analyze the health care reform bill that the Vermont legislature passed. Finally, the article discusses the campaign's local and national impact. PMID- 22773095 TI - Bridging international law and rights-based litigation: mapping health-related rights through the development of the Global Health and Human Rights Database. AB - The O'Neill Institute for National and Global Health Law at Georgetown University, the World Health Organization, and the Lawyers Collective have come together to develop a searchable Global Health and Human Rights Database that maps the intersection of health and human rights in judgments, international and regional instruments, and national constitutions. Where states long remained unaccountable for violations of health-related human rights, litigation has arisen as a central mechanism in an expanding movement to create rights-based accountability. Facilitated by the incorporation of international human rights standards in national law, this judicial enforcement has supported the implementation of rights-based claims, giving meaning to states' longstanding obligations to realize the highest attainable standard of health. Yet despite these advancements, there has been insufficient awareness of the international and domestic legal instruments enshrining health-related rights and little understanding of the scope and content of litigation upholding these rights. As this accountability movement evolves, the Global Health and Human Rights Database seeks to chart this burgeoning landscape of international instruments, national constitutions, and judgments for health-related rights. Employing international legal research to document and catalogue these three interconnected aspects of human rights for the public's health, the Database's categorization by human rights, health topics, and regional scope provides a comprehensive means of understanding health and human rights law. Through these categorizations, the Global Health and Human Rights Database serves as a basis for analogous legal reasoning across states to serve as precedents for future cases, for comparative legal analysis of similar health claims in different country contexts, and for empirical research to clarify the impact of human rights judgments on public health outcomes. PMID- 22773096 TI - Between the court and the clinic: lawsuits for medicines and the right to health in Brazil. AB - BACKGROUND: The Brazilian Constitution states: "Health is the right of all persons and the duty of the State." Yet individuals in Brazil frequently face barriers to health prevention and treatment. One response to these barriers has been a "judicialization" of the right to health, with an increasing number of patients suing the government for access to medicines. OBJECTIVE/METHODS: This study uses a mixed methods approach to identify trends in lawsuits for medicines in the southern state of Rio Grande do Sul (RS) and to characterize patient plaintiffs. Electronic registries were used to determine the number of health lawsuits filed between 2002 and 2009. In-depth interviews were conducted with thirty patient-plaintiffs, and 1,080 lawsuits for medicines under review between September 1, 2008 and July 31, 2009 were analyzed to assess socio demographic, medical, and legal characteristics of patient-plaintiffs. RESULTS: Between 2002 and 2009, the annual number of health-related lawsuits against the state of RS increased from 1,126 to 17,025. In 2009, 72% of lawsuits sought access to medicines. In-depth interviews revealed that patients are desperate to access medicines for chronic and advanced diseases, and often turn to the courts as a last resort. Among the 1,080 lawsuits examined, patient-plaintiffs were more likely to be older than 45 years (68%), retired or unemployed (71%), and low income (among those who reported income, 53% (n=350) earned less than the national minimum wage). Fifty-nine percent of all cases were represented by public defenders. Plaintiffs reported 1,615 diseases and requested 2.8 drugs on average (range 1-16). Sixty-five percent of the requested drugs were on government pharmaceutical distribution lists; 78% of the 254 drugs on these lists were requested. In 95% of the cases analyzed, district courts ruled in favor of plaintiffs. Among the 917 cases with a final state high court ruling, 89% were in favor of the plaintiff. In justifying their rulings, judges most frequently cited the government's obligation under the Constitution's provision of a right to health. DISCUSSION: Right-to-health litigation is a widespread practice in southern Brazil. Government pharmaceutical programs are struggling to fulfill their goal of expanded access and rational use of medicines, and poor patients are leveraging public legal assistance and a receptive judiciary to hold the state accountable to their medical needs. "Judicialization" is an alternative pathway for accessing health care, increasingly understood as access to medicines of all kinds. Tracking the health outcomes and budgetary impacts of right to health court cases could help inform adequate treatment policy and evaluate trends in access. PMID- 22773097 TI - Pillars for progress on the right to health: harnessing the potential of human rights through a Framework Convention on Global Health. AB - Ever more constitutions incorporate the right to health, courts continue to expand their right to health jurisprudence, and communities and civil society increasingly turn to the right to health in their advocacy. Yet the right remains far from being realized. Even with steady progress on numerous fronts of global health, vast inequities at the global and national levels persist, and are responsible for millions of deaths annually. We propose a four-part approach to accelerating progress towards fulfilling the right to health: 1) national legal and policy reform, incorporating right to health obligations and principles including equity, participation, and accountability in designing, implementing, and monitoring the health sector, as well as an all-of-government approach in advancing the public's health; 2) litigation, using creative legal strategies, enhanced training, and promotion of progressive judgments to increase courts' effectiveness in advancing the right to health; 3) civil society and community engagement, empowering communities to understand and claim this right and building the capacity of right to health organizations; and 4) innovative global governance for health, strengthening World Health Organization leadership on health and human rights, further clarifying the international right to health, ensuring sustained and scalable development assistance, and conforming other international legal regimes (e.g., trade, intellectual property, and finance) to health and human rights norms. We offer specific steps to advance each of these areas, including how a new global health treaty, a Framework Convention on Global Health, could help construct these four pillars. PMID- 22773098 TI - New Zealand's National Health and Disability Advocacy Service: a successful model of advocacy. AB - This paper, in exploring both the debate and practice of advocacy, uses the National Health and Disability Advocacy Service in New Zealand to describe a successful model of advocacy that is based on the concept of empowerment practiced in an independent environment and strengthened by an enforceable framework of consumer rights. PMID- 22773099 TI - Brazilian policy responses to violence against women: government strategy and the help-seeking behaviors of women who experience violence. AB - Over the past three decades, international covenants have been signed and countries have implemented strategies and legislation to address violence against women. Concurrently, strong evidence on the magnitude and impact of violence against women has emerged from around the world. Despite a growing understanding of factors that may influence women's vulnerability to violence and its effects, key questions about intervention options persist. Using evidence from a WHO household survey on domestic violence, our paper discusses women's help-seeking patterns and considers these findings in relation to Brazil's policies and strategies on violence against women. For the WHO survey, data from a large urban center (the city of Sao Paulo) and from a rural region (Zona da Mata Pernambucana [ZMP]) was collected. Findings from this survey indicate that in Sao Paulo, only 33.8% of women who experienced intimate partner violence (IPV) sought help from a formal service provider, including health, legal, social, or women's support services; in the Forest Zone of the State of Pernambuco, an even smaller proportion (17.1%) sought formal assistance. The majority of women were likely to contact only informal sources of support, such as family, friends, and neighbors. Women who used formal services were primarily those who experienced more severe levels of violence, were severely injured, had children who witnessed the violence, or whose work was disrupted by the violence. Although Brazil adopted progressive laws and national and local strategies to address violence against women (VAW), messages about violence and equality need to reach informal networks and the wider community in order to national anti-violence policies to be successful in supporting women before violence becomes intolerable.. To translate international standards and national policies into actions that genuinely reach women experiencing violence, states must carefully consider evidence on women's options and decision making. PMID- 22773100 TI - Child rights, right to water and sanitation, and human security. AB - The article explores the intersection between child rights, water scarcity, sanitation, and the human security paradigm. The recognition of child rights has been advanced through the 1989 Convention on the Rights of the Child and other international legal instruments, while water rights are increasingly affirmed in international law and through the historic July 2010 United Nations General Assembly resolution that strengthened the legal foundation for water security and human rights. Yet there remains a development gap in terms of child access to clean and secure water sources for basic human development needs. The human security paradigm provides a legal and humanitarian foundation for the extension of child rights related to water and sanitation. PMID- 22773101 TI - Filling the gap: a learning network for health an human rights in the Western Cape, South Africa. AB - We draw on the experience of a Learning Network for Health and Human Rights (LN) involving collaboration between academic institutions and civil society organizations in the Western Cape, South Africa, aimed at identifying and disseminating best practice related to the right to health. The LN's work in materials development, participatory research, training and capacity-building for action, and advocacy for intervention illustrates important lessons for human rights practice. These include (i) the importance of active translation of knowledge and awareness into action for rights to be made real; (ii) the potential tension arising from civil society action, which might relieve the state of its obligations by delivering services that should be the state's responsibility-and hence the importance of emphasizing civil society's role in holding services accountable in terms of the right to health; (iii) the role of civil society organizations in filling a gap related to obligations to promote rights; (iv) the critical importance of networking and solidarity for building civil society capacity to act for health rights. Evidence from evaluation of the LN is presented to support the argument that civil society can play a key role in bridging a gap between formal state commitment to creating a human rights culture and realizing services and policies that enable the most vulnerable members of society to advance their health. Through access to information and the creation of spaces, both for participation and as a safe environment in which learning can be turned into practice, the agency of those most affected by rights violations can be redressed. We argue that civil society agency is critical to such action. PMID- 22773102 TI - Functional characterization of an active Rag-like transposase. AB - The formation of diverse immunoglobulin genes results in part from Rag protein mediated DNA double-strand breaks at the edges of immunoglobulin gene segments, followed by combinatorial reassembly of these segments. We report that a Transib transposase from the insect Helicoverpa zea is active in vitro and that its breakage and joining activities mimic those of Rag, providing strong evidence that Rag and Transib transposases were derived from a common progenitor. PMID- 22773103 TI - LEDGF (p75) promotes DNA-end resection and homologous recombination. AB - Lens epithelium-derived growth factor p75 splice variant (LEDGF) is a chromatin binding protein known for its antiapoptotic activity and ability to direct human immunodeficiency virus into active transcription units. Here we show that LEDGF promotes the repair of DNA double-strand breaks (DSBs) by the homologous recombination repair pathway. Depletion of LEDGF impairs the recruitment of C terminal binding protein interacting protein (CtIP) to DNA DSBs and the subsequent CtIP-dependent DNA-end resection. LEDGF is constitutively associated with chromatin through its Pro-Trp-Trp-Pro (PWWP) domain that binds preferentially to epigenetic methyl-lysine histone markers characteristic of active transcription units. LEDGF binds CtIP in a DNA damage-dependent manner, thereby enhancing its tethering to the active chromatin and facilitating its access to DNA DSBs. These data highlight the role of PWWP-domain proteins in DNA repair and provide a molecular explanation for the antiapoptotic and cancer cell survival-activities of LEDGF. PMID- 22773104 TI - The translin-TRAX complex (C3PO) is a ribonuclease in tRNA processing. AB - Conserved translin-TRAX complexes, also known as C3POs, have been implicated in many biological processes, but how they function remains unclear. Recently, C3PO was shown to be an endoRNase that promotes RNA interference (RNAi) in animal cells. Here, we show that C3PO does not play a significant role in RNAi in the filamentous fungus Neurospora crassa. Instead, the Neurospora C3PO functions as an RNase that removes the 5' pre-tRNA fragments after the processing of pre-tRNAs by RNase P. In addition, translin and trax mutants have elevated levels of tRNA and protein translation and are more resistant to a cell death-inducing agent. Finally, we show that C3PO is also involved in tRNA processing in mouse embryonic fibroblast cells. This study identifies the endogenous RNA substrates of C3PO and provides a potential explanation for its roles in apparently diverse biological processes. PMID- 22773105 TI - Cyclic AMP regulation of protein lysine acetylation in Mycobacterium tuberculosis. AB - Protein lysine acetylation networks can regulate central processes such as carbon metabolism and gene expression in bacteria. In Escherichia coli, cyclic AMP (cAMP) regulates protein lysine acetyltransferase (PAT) activity at the transcriptional level, but in Mycobacterium tuberculosis, fusion of a cyclic nucleotide-binding domain to a Gcn5-like PAT domain enables direct cAMP control of protein acetylation. Here we describe the allosteric activation mechanism of M. tuberculosis PAT. The crystal structures of the autoinhibited and cAMP activated PAT reveal that cAMP binds to a cryptic site in the regulatory domain that is over 32 A from the catalytic site. An extensive conformational rearrangement relieves this autoinhibition by means of a substrate-mimicking lid that covers the protein-substrate binding surface. A steric double latch couples the domains by harnessing a classic, cAMP-mediated conformational switch. The structures suggest general features that enable the evolution of long-range communication between linked domains. PMID- 22773106 TI - Development traumatic brain injury computer user interface for disaster area in Indonesia supported by emergency broadband access network. AB - Disasters bring consequences of negative impacts on the environment and human life. One of the common cause of critical condition is traumatic brain injury (TBI), namely, epidural (EDH) and subdural hematoma (SDH), due to downfall hard things during earthquake. We proposed and analyzed the user response, namely neurosurgeon, general doctor/surgeon and nurse when they interacted with TBI computer interface. The communication systems was supported by TBI web based applications using emergency broadband access network with tethered balloon and simulated in the field trial to evaluate the coverage area. The interface consisted of demography data and multi tabs for anamnesis, treatment, follow up and teleconference interfaces. The interface allows neurosurgeon, surgeon/general doctors and nurses to entry the EDH and SDH patient's data during referring them on the emergency simulation and evaluated based on time needs and their understanding. The average time needed was obtained after simulated by Lenovo T500 notebook using mouse; 8-10 min for neurosurgeons, 12-15 min for surgeons/general doctors and 15-19 min for nurses. By using Think Pad X201 Tablet, the time needed for entry data was 5-7 min for neurosurgeon, 7-10 min for surgeons/general doctors and 12-16 min for nurses. We observed that the time difference was depending on the computer type and user literacy qualification as well as their understanding on traumatic brain injury, particularly for the nurses. In conclusion, there are five data classification for simply TBI GUI, namely, 1) demography, 2) specific anamnesis for EDH and SDH, 3) treatment action and medicine of TBI, 4) follow up data display and 5) teleneurosurgery for streaming video consultation. The type of computer, particularly tablet PC was more convenient and faster for entry data, compare to that computer mouse touched pad. Emergency broadband access network using tethered balloon is possible to be employed to cover the communications systems in disaster area. PMID- 22773107 TI - Benzene-1,3,5-tricarboxamide: a versatile ordering moiety for supramolecular chemistry. AB - After their first synthesis in 1915 by Curtius, benzene-1,3,5-tricarboxamides (BTAs) have become increasingly important in a wide range of scientific disciplines. Their simple structure and wide accessibility in combination with a detailed understanding of their supramolecular self-assembly behaviour allow full utilization of this versatile, supramolecular building block in applications ranging from nanotechnology to polymer processing and biomedical applications. While the opportunities in the former cases are connected to the self-assembly of BTAs into one-dimensional, nanometer-sized rod like structures stabilised by threefold H-bonding, their multivalent nature drives applications in the biomedical field. This review summarises the different types of BTAs that appeared in the recent literature and the applications they have been evaluated in. Currently, the first commercial applications of BTAs are emerging. The adaptable nature of this multipurpose building block promises a bright future. PMID- 22773108 TI - Precision of novel radiological methods in relation to resurfacing humeral head implants: assessment by radiostereometric analysis, DXA, and geometrical analysis. AB - BACKGROUND: Resurfacing humeral head implants (RHHI) are used to preserve bone stock and restore normal anatomy in the osteoarthritic shoulder joint. The purpose of this study was: (1) to describe the use of novel radiological methods in relation to evaluation of RHHI; (2) to estimate the precision of these methods; and (3) to present preliminary clinical and radiological results at 6 months follow-up after Copeland and Global Cap RHHI. METHODS: Twenty-one patients (10 females) at a mean age of 64 (39-82) years and with shoulder osteoarthritis were randomized to a Copeland (n = 11) or Global C.A.P (n = 10) RHHI. Migration of the RHHI was analyzed with radiostereometric analysis (RSA), and bone mineral density (BMD) was measured with dual energy X-ray absorptiometry (DXA). The length of gleno-humeral offset (LGHO) was measured on radiographs. The patients were followed clinically with questionnaires. RESULTS: Precision of the radiological methods was high for the LGHO and acceptable for RSA and for DXA. At 6 months, shoulder function had improved significantly for both RHHI groups. LGHO increased significantly for the Copeland RHHI and was slightly reduced for the Global C.A.P. RHHI. The implant migration and BMD change around the implant from baseline until 6 months follow-up was comparable for both RHHI. CONCLUSION: Radiostereometric analysis and DXA can be used for evaluation of RHHI, but expectedly with a lower precision as compared to standards of TKA or THA. Geometric analysis of the prosthetic shoulder is precise. We interpret that the early radiological and clinical results of the two RHHI are comparable. PMID- 22773110 TI - Laboratory tests for controlling poultry red mites (Dermanyssus gallinae) with predatory mites in small 'laying hen' cages. AB - To assess their potential to control poultry red mites (Dermanyssus gallinae), we tested selected predaceous mites (Androlaelaps casalis and Stratiolaelaps scimitus) that occur naturally in wild bird nests or sometimes spontaneously invade poultry houses. This was done under laboratory conditions in cages, each with 2-3 laying hens, initially 300 poultry red mites and later the release of 1,000 predators. These small-scale tests were designed to prevent mite escape from the cages and they were carried out in three replicates at each of three temperature regimes: 26, 30 (constant day and night) and 33-25 degrees C (day night cycle). After 6 weeks total population sizes of poultry red mites and predatory mites were assessed. For the temperature regimes of 26 and 33/25 degrees C S. scimitus reduced the poultry red mite population relative to the control experiments by a factor 3 and 30, respectively, and A. casalis by a factor of 18 and 55, respectively. At 30 degrees C the predators had less effect on red mites, with a reduction of 1.3-fold for S. scimitus and 5.6-fold for A. casalis. This possibly reflected hen manure condition or an effect of other invertebrates in the hen feed. Poultry red mite control was not negatively affected by temperatures as high as 33 degrees C and was always better in trials with A. casalis than in those with S. scimitus. In none of the experiments predators managed to eradicate the population of poultry red mites. This may be due to a prey refuge effect since most predatory mites were found in and around the manure tray at the bottom of the cage, whereas most poultry red mites were found higher up in the cage (i.e. on the walls, the cover, the perch, the nest box and the food box). The efficacy of applying predatory mites in the poultry industry may be promoted by reducing this refuge effect, boosting predatory mite populations using alternative prey and prolonged predator release devices. Biocontrol success, however, will strongly depend on how the poultry is housed in practice (free range, cage or aviary systems) and on which chemicals are applied to disinfect poultry houses and to control other pests. PMID- 22773109 TI - Modest increase in peak VO2 is related to better clinical outcomes in chronic heart failure patients: results from heart failure and a controlled trial to investigate outcomes of exercise training. AB - BACKGROUND: The prognostic ability of a single measurement of peak oxygen uptake (VO(2)) is well established in patients with chronic heart failure. The relation between a change in peak VO(2) and clinical outcomes is not well defined. METHODS AND RESULTS: This investigation determined whether an increase in peak VO(2) was associated with a lower risk of the primary end point of time to all-cause mortality or all-cause hospitalization and 3 secondary end points. In Heart Failure and a Controlled Trial to Investigate Outcomes of Exercise Training, an exercise training trial for patients with systolic heart failure, cardiopulmonary exercise tests were performed at baseline and ~3 months later in 1620 participants. Median peak VO(2) in the combined sample increased from 15.0 (11.9 18.0 Q1-Q3) to 15.4 (12.3-18.7 Q1-Q3) mL.kg(-1).min(-1). Every 6% increase in peak VO(2,) adjusted for other significant predictors, was associated with a 5% lower risk of the primary end point (hazard ratio=0.95; CI=0.93-0.98; P<0.001); a 4% lower risk of the secondary end point of time to cardiovascular mortality or cardiovascular hospitalization (hazard ratio=0.96; CI=0.94-0.99; P<0.001); an 8% lower risk of cardiovascular mortality or heart failure hospitalization (hazard ratio=0.92; CI=0.88-0.96; P<0.001); and a 7% lower all-cause mortality (hazard ratio=0.93; CI=0.90-0.97; P<0.001). CONCLUSIONS: Among patients with chronic systolic heart failure, a modest increase in peak VO(2) over 3 months was associated with a more favorable outcome. Monitoring the change in peak VO(2) for such patients may have benefit in assessing prognosis. PMID- 22773111 TI - Localization of new peptidoglycan at poles in Bacillus mycoides, a member of the Bacillus cereus group. AB - Bacillus mycoides is a sporogenic Gram-positive soil bacillus of the B. cereus group. This bacillus, which forms hyphal colonies, is composed of cells connected in filaments that make up bundles and turn clock- or counterclockwise depending on the strain. A thick peptidoglycan wall gives the rod cells of these bacilli strength and shape. One approach used to study peptidoglycan neoformation in Gram positives exploits the binding properties of antibiotics such as vancomycin and ramoplanin to nascent peptidoglycan, whose localization in the cell is monitored by means of a fluorescent tag. When we treated B. mycoides strains with BODIPY vancomycin, we found the expected accumulation of fluorescence at the midcell septa and localization along the cell sidewall in small foci distributed quite uniformly. Intense fluorescence was also observed at the poles of many cells, more clearly visible at the outer edges of the cell chains. The unusual abundance of peptidoglycan intermediates at the cell poles after cell separation suggests that the construction process of this structure is different from that of B. subtilis, in which the free poles are rarely reactive to vancomycin. PMID- 22773112 TI - Tips from the world's oldest living body builder. PMID- 22773114 TI - Predicting nitrogen loading with land-cover composition: how can watershed size affect model performance? AB - Watershed-wide land-cover proportions can be used to predict the in-stream non point source pollutant loadings through regression modeling. However, the model performance can vary greatly across different study sites and among various watersheds. Existing literature has shown that this type of regression modeling tends to perform better for large watersheds than for small ones, and that such a performance variation has been largely linked with different interwatershed landscape heterogeneity levels. The purpose of this study is to further examine the previously mentioned empirical observation based on a set of watersheds in the northern part of Georgia (USA) to explore the underlying causes of the variation in model performance. Through the combined use of the neutral landscape modeling approach and a spatially explicit nutrient loading model, we tested whether the regression model performance variation over the watershed groups ranging in size is due to the different watershed landscape heterogeneity levels. We adopted three neutral landscape modeling criteria that were tied with different similarity levels in watershed landscape properties and used the nutrient loading model to estimate the nitrogen loads for these neutral watersheds. Then we compared the regression model performance for the real and neutral landscape scenarios, respectively. We found that watershed size can affect the regression model performance both directly and indirectly. Along with the indirect effect through interwatershed heterogeneity, watershed size can directly affect the model performance over the watersheds varying in size. We also found that the regression model performance can be more significantly affected by other physiographic properties shaping nitrogen delivery effectiveness than the watershed land-cover heterogeneity. This study contrasts with many existing studies because it goes beyond hypothesis formulation based on empirical observations and into hypothesis testing to explore the fundamental mechanism. PMID- 22773115 TI - Recreational system optimization to reduce conflict on public lands. AB - In response to federal administrative rule, the Tahoe National Forest (TNF), California, USA engaged in trail-route prioritization for motorized recreation (e.g., off-highway-vehicles) and other recreation types. The prioritization was intended to identify routes that were suitable and ill-suited for maintenance in a transportation system. A recreational user survey was conducted online (n = 813) for user preferences for trail system characteristics, recreational use patterns, and demographics. Motorized trail users and non-motorized users displayed very clear and contrasting preferences for the same system. As has been found by previous investigators, non-motorized users expressed antagonism to motorized use on the same recreational travel system, whereas motorized users either supported multiple-use routes or dismissed non-motorized recreationists' concerns. To help the TNF plan for reduced conflict, a geographic information system (GIS) based modeling approach was used to identify recreational opportunities and potential environmental impacts of all travel routes. This GIS based approach was based on an expert-derived rule set. The rules addressed particular environmental and recreation concerns in the TNF. Route segments were identified that could be incorporated into minimal-impact networks to support various types of recreation. The combination of potential impacts and user benefits supported an optimization approach for an appropriate recreational travel network to minimize environmental impacts and user-conflicts in a multi purpose system. PMID- 22773113 TI - The "Janus-faced role" of autophagy in neuronal sickness: focus on neurodegeneration. AB - The mature brain is a highly dynamic organ that constantly changes its organization by destroying and forming new connections. Collectively, these changes are referred to as brain plasticity and are associated with functional changes, such as memory, addiction, and recovery of function after brain damage. Neuronal plasticity is sustained by the fine regulation of protein synthesis and organelle biogenesis and their degradation to ensure efficient turnover. Thus, autophagy, as quality control mechanism of proteins and organelles in neurons, is essential to their physiology and pathology. Here, we review recent several findings proving that defects in autophagy affect neuronal function and impair functional recovery after brain insults, contributing to neurodegeneration, in chronic and acute neurological disorders. Thus, an understanding of the molecular mechanisms by which the autophagy machinery is finely regulated might accelerate the development of therapeutic interventions in many neurological disorders for which no cure is available. PMID- 22773116 TI - UBioLab: a web-laboratory for ubiquitous in-silico experiments. AB - The huge and dynamic amount of bioinformatic resources (e.g., data and tools) available nowadays in Internet represents a big challenge for biologists -for what concerns their management and visualization- and for bioinformaticians -for what concerns the possibility of rapidly creating and executing in-silico experiments involving resources and activities spread over the WWW hyperspace. Any framework aiming at integrating such resources as in a physical laboratory has imperatively to tackle -and possibly to handle in a transparent and uniform way- aspects concerning physical distribution, semantic heterogeneity, co existence of different computational paradigms and, as a consequence, of different invocation interfaces (i.e., OGSA for Grid nodes, SOAP for Web Services, Java RMI for Java objects, etc.). The framework UBioLab has been just designed and developed as a prototype following the above objective. Several architectural features -as those ones of being fully Web-based and of combining domain ontologies, Semantic Web and workflow techniques- give evidence of an effort in such a direction. The integration of a semantic knowledge management system for distributed (bioinformatic) resources, a semantic-driven graphic environment for defining and monitoring ubiquitous workflows and an intelligent agent-based technology for their distributed execution allows UBioLab to be a semantic guide for bioinformaticians and biologists providing (i) a flexible environment for visualizing, organizing and inferring any (semantics and computational) "type" of domain knowledge (e.g., resources and activities, expressed in a declarative form), (ii) a powerful engine for defining and storing semantic-driven ubiquitous in-silico experiments on the domain hyperspace, as well as (iii) a transparent, automatic and distributed environment for correct experiment executions. PMID- 22773117 TI - Proinflammatory cytokine levels in saliva in patients with burning mouth syndrome before and after treatment with low-level laser therapy. AB - The aim of this study was to determine the levels of proinflammatory tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) cytokines in whole unstimulated saliva in subjects with burning mouth syndrome (BMS) before and after treatment with low-level laser therapy (LLLT). BMS is characterized by a continuous, painful burning sensation in a clinically normal-appearing oral mucosa. A sample consisting of 40 consecutive subjects was selected on a voluntary basis from the pool of patients who presented for diagnosis and treatment of BMS at the Oral Medicine Unit of the Faculty of Medicine of the University of Rijeka. For determination of salivary levels of TNF-alpha and IL-6, ELISA (Sigma Immunochemicals, St. Louis, MO, USA) was performed to determine the salivary levels of TNF-alpha and IL-6. After 4 weeks of LLLT, the salivary levels of TNF-alpha and IL-6 in the experimental group decreased significantly (p < 0.001). There was no significant difference in the experimental group regarding visual analogue scale. PMID- 22773118 TI - Wool traits of three sympatric sheep populations in Chiapas Region, Mexico. AB - A total of 344 pure animals, representing seven American and South European breeds (White Chiapas Blanca, Brown Chiapas Cafe, Black Chiapas Negra, Churra Badana, Churra da Terra Quente, Chilean Latxa, and Spanish Merino), were randomly sampled and wool evaluated for isoalcohol scouring yield, length, and proportion for each type of fiber (long-thick, short-thin, and kemp), average of fiber diameter, and F30 (percentage of fibers with a diameter of >30 MUm). The objective of this study was to characterize these breeds according to their wool traits. A low percentage of the phenotypic variability in the analyzed animals was due to differences among breeds, and that the largest part of that variability is due to differences within breeds. The obtained topology in the principal coordinates analysis showed the grouping of the three Chiapas breeds clearly separated, but the similarity with their original breed was only evident for Brown Chiapas Cafe. The three Chiapas sheep breeds must be regarded as clearly sympatric populations. PMID- 22773119 TI - The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway. AB - Mutations in leucine-rich repeat kinase 2 (LRRK2) are a major cause of familial Parkinsonism, and the G2019S mutation of LRRK2 is one of the most prevalent mutations. The deregulation of autophagic processes in nerve cells is thought to be a possible cause of Parkinson's disease (PD). In this study, we observed that G2019S mutant fibroblasts exhibited higher autophagic activity levels than control fibroblasts. Elevated levels of autophagic activity can trigger cell death, and in our study, G2019S mutant cells exhibited increased apoptosis hallmarks compared to control cells. LRRK2 is able to induce the phosphorylation of MAPK/ERK kinases (MEK). The use of 1,4-diamino-2,3-dicyano-1,4-bis[2 aminophenylthio]butadiene (U0126), a highly selective inhibitor of MEK1/2, reduced the enhanced autophagy and sensibility observed in G2019S LRRK2 mutation cells. These data suggest that the G2019S mutation induces autophagy via MEK/ERK pathway and that the inhibition of this exacerbated autophagy reduces the sensitivity observed in G2019S mutant cells. PMID- 22773121 TI - Nutritional support in patients with GVHD of the digestive tract: state of the art. AB - An important complication of allo-SCT is GVHD, which commonly affects the skin, liver and digestive tract. Clinical symptoms of GVHD of the digestive tract (GVHD DT) include excessive diarrhoea, abdominal pain and cramps, nausea and vomiting, gastrointestinal bleeding, dysphagia, and weight loss. Treatment is complicated and regarding nutritional support, only a few guidelines are available. Our aim was to critically appraise the literature on nutritional assessment, nutritional status and nutritional support for patients with GVHD-DT. Evidence shows that GVHD-DT is often associated with malnutrition, protein losing enteropathy, magnesium derangements, and deficiencies of zinc, vitamin B12 and vitamin D. Limited evidence exists on derangements of magnesium, resting energy expenditure, bone mineral density and pancreatic function, and some beneficial effects of n-3 polyunsaturated fatty acids and pancreatic enzyme replacement therapy. Expert opinions recommend adequate amounts of energy, at least 1.5 g protein/kg body weight, supplied by total parenteral nutrition in cases of severe diarrhoea. When diarrhoea is <500 mL a day, a stepwise oral upgrade diet can be followed. No studies exist on probiotics, prebiotics, dietary fibre and immunonutrition in GVHD-DT patients. Future research should focus on absorption capacity, vitamin and mineral status, and nutritional support strategies. PMID- 22773120 TI - MicroRNA-338 regulates the axonal expression of multiple nuclear-encoded mitochondrial mRNAs encoding subunits of the oxidative phosphorylation machinery. AB - MicroRNAs (miRNAs) constitute a novel class of small, non-coding RNAs that act as post-transcriptional regulators of gene expression. Remarkably, it has been shown that these small molecules can coordinately regulate multiple genes coding for proteins with related cellular functions. Previously, we reported that brain specific miR-338 modulates the axonal expression of cytochrome c oxidase IV (COXIV), a nuclear-encoded mitochondrial protein that plays a key role in oxidative phosphorylation and axonal function. Here, we report that ATP synthase (ATP5G1), like COXIV mRNA, contains a putative miR-338 binding site, and that modulation of miR-338 levels in the axon results in alterations in both COXIV and ATP5G1 expression. Importantly, miR-338 modulation of local COXIV and ATP5G1 expression has a marked effect on axonal ROS levels, as well as axonal growth. These findings point to a mechanism by which miR-338 modulates local energy metabolism through the coordinate regulation of the expression of multiple nuclear-encoded mitochondrial mRNAs in the axon. PMID- 22773123 TI - G-CSF plus plerixafor (Mozobil) to mobilize hematopoietic stem cells in patients with thrombocytopenia or leukopenia prior to auto-SCT. PMID- 22773122 TI - Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients. AB - To enhance the therapeutic index of allogeneic hematopoietic SCT (HSCT), we immunized 10 HLA-matched sibling donors before stem cell collection with recipient-derived clonal myeloma Ig, idiotype (Id), as a tumor antigen, conjugated with keyhole limpet hemocyanin (KLH). Vaccinations were safe in donors and recipients. Donor-derived KLH- and Id-specific humoral and central and effector memory T-cell responses were detectable by day 30 after HSCT and were boosted by post-transplant vaccinations at 3 months in most recipients. One patient died before booster vaccinations. Specifically, after completing treatment, 8/9 myeloma recipients had persistent Id-specific immune responses and 5/9 had improvement in disease status. Although regulatory T cells increased after vaccination, they did not impact immune responses. At a median potential follow-up period of 74 months, 6 patients are alive, the 10 patients have a median PFS of 28.5 months and median OS has not been reached. Our results provide proof of principle that neoantigen and tumor antigen-specific humoral and cellular immunity could be safely induced in HSCT donors and passively transferred to recipients. This general strategy may be used to reduce relapse of malignancies and augment protection against infections after allogeneic HSCT. PMID- 22773124 TI - Incidence and risk factors of EBV reactivation after unrelated cord blood transplantation: a Eurocord and Societe Francaise de Greffe de Moelle-Therapie Cellulaire collaborative study. AB - EBV viremia and post-transplantation lymphoproliferative disorders (PTLDs) have been associated with high mortality rates after allogeneic hematopoietic SCT (allo-HSCT). Few retrospective studies, without EBV load monitoring postulated that umbilical cord blood transplantation (UCBT) might be associated with high incidence of EBV events. We retrospectively studied 175 UCBT recipients for whom RQ-PCR was used to monitor EBV blood load at least once a week during the first 3 months after UCBT. Median age was 23 years, 74% had leukemia. Conditioning was myeloablative in 54% and reduced intensity conditioning (RIC) was used in 46%. A total of 24 patients presented an EBV reactivation. For 15 patients, the reactivation occurred during the first 100 days (cumulative incidence: 8%) and included 4 EBV-PTLD. Rituximab as preemptive treatment was used in 12 of these 15 patients. In univariate analysis, the increased risk of early EBV reactivation was associated with RIC in combination with antithymocyte globulin (P=0.03) and previous history of auto-HSCT (P=0.01). Multivariate analysis did not find any independent risk factor. EBV reactivation as time-dependent covariate was not statistically associated with survival. Therefore, EBV events were not major complications after UCBT when EBV load is weekly monitored and preemptive treatment started. PMID- 22773125 TI - The impact of center experience on results of reduced intensity: allogeneic hematopoietic SCT for AML. An analysis from the Acute Leukemia Working Party of the EBMT. AB - Allogeneic hematopoietic SCT with reduced-intensity conditioning (RIC-HSCT) is increasingly adopted for the treatment of older adults with AML. Our goal was to verify for the first time, if center experience influences outcome of RIC-HSCT. Results of 1413 transplantations from HLA-matched related or unrelated donors for adult patients with AML in first CR were analyzed according to the level of center activity. Transplants were performed in 203 European centers between 2001 and 2007. The 2-year probability of leukemia-free survival (LFS) after RIC-HSCT performed in centers with the lowest activity (< or =15 procedures/7 years) was 43+/-3% compared with 55+/-2% in the remainder (P<0.001). The incidence of non relapse mortality (NRM) was 24+/-3% and 15+/-1% (P=0.004), whilst relapse rate was 33+/-3% and 31+/-1% (P=0.33), respectively. In a multivariate model, adjusted for other prognostic factors, low RIC-HSCT activity was associated with decreased chance of LFS (hazard ratio (HR)=0.64; P<0.001) and increased risk of NRM (HR=1.47, P=0.04) and relapse (HR=1.41, P=0.01). Center experience is a very important predictor of outcome and should be considered in future analyses evaluating the results of RIC-HSCT. The reasons why centers with low RIC-HSCT activity have worse outcomes should be further investigated. PMID- 22773126 TI - Costs of autologous and allogeneic hematopoietic cell transplantation in the United States: a study using a large national private claims database. AB - There is a lack of multi-center cost-identification studies for hematopoietic cell transplantation (HCT). We used a single longitudinal administrative claims database representing a national, commercially insured population to evaluate the feasibility of identifying HCT recipients and to establish a cohort of autologous and allogeneic HCT recipients to study inpatient and outpatient direct medical costs from transplant hospitalization through first 100 days post transplantation. Using ICD-9 procedure and diagnosis codes, we identified 3365 patients who had received their first transplant in the United States between 2007 and 2009 (autologous, 1678, allogeneic, 1320, graft source not specified, 367). The median 100-day total costs for autologous HCT were $99,899 (interquartile range (IQR), $73,914-140,555), and for allogeneic HCT were $203,026 (IQR, $141,742-316 ,426). The majority of costs (>75%) occurred during the initial transplant hospitalization for both autologous and allogeneic HCT recipients. Costs were greater among pediatric (< or =20 years) compared with adult (>20 years) recipients and this difference was more pronounced with allogeneic HCT. Using a claims database representing a national HCT population, we highlight the high costs associated with autologous and allogeneic HCT. Our study lays the foundation for using claims data for future research on economic aspects of HCT. PMID- 22773127 TI - Stem cell mobilization in heavily pretreated multiple myeloma patients with prior high dose melphalan and auto-SCT. PMID- 22773128 TI - Suicide after hematopoietic SCT: the story of AG. PMID- 22773129 TI - Allogeneic hematopoietic stem cell donation-standardized assessment of donor outcome data: a consensus statement from the Worldwide Network for Blood and Marrow Transplantation (WBMT). AB - The number of allogeneic hematopoietic SCTs performed globally each year continues to increase, paralleled by an increased demand for donors of therapeutic cells. Donor characteristics and collection procedures have undergone major changes during recent decades, and further changes are foreseen. Information on short- and long-term donor outcomes is of crucial importance to ensure maximal donor safety and availability. Current data, predominantly from unrelated donors, give reliable information on the frequent early events associated with donation-most of them of mild-to-moderate intensity. Information on the type and relative risk of serious adverse reactions is more limited. Moreover, only few data exist on long-term donor outcome. On the basis of this need, recommendations for a minimum data set for prospective donor follow-up were developed in a workshop with the participation of an international group of investigators actively involved in allogeneic stem cell donation under the auspices of and approved by the Worldwide Network for Blood and Marrow Transplantation. Establishment of a standardized global follow-up for both, related and unrelated, donors will enable monitoring of the short- and long-term safety profiles of hematopoietic cell donation and form a solid basis for future donor selection and counseling. PMID- 22773130 TI - Molecular recognition: from solution science to nano/materials technology. AB - In the 25 years since its Nobel Prize in chemistry, supramolecular chemistry based on molecular recognition has been paid much attention in scientific and technological fields. Nanotechnology and the related areas seek breakthrough methods of nanofabrication based on rational organization through assembly of constituent molecules. Advanced biochemistry, medical applications, and environmental and energy technologies also depend on the importance of specific interactions between molecules. In those current fields, molecular recognition is now being re-evaluated. In this review, we re-examine current trends in molecular recognition from the viewpoint of the surrounding media, that is (i) the solution phase for development of basic science and molecular design advances; (ii) at nano/materials interfaces for emerging technologies and applications. The first section of this review includes molecular recognition frontiers, receptor design based on combinatorial approaches, organic capsule receptors, metallo-capsule receptors, helical receptors, dendrimer receptors, and the future design of receptor architectures. The following section summarizes topics related to molecular recognition at interfaces including fundamentals of molecular recognition, sensing and detection, structure formation, molecular machines, molecular recognition involving polymers and related materials, and molecular recognition processes in nanostructured materials. PMID- 22773131 TI - Biodegradation kinetic constants and sorption coefficients of micropollutants in membrane bioreactors. AB - In order to elucidate the capability of biomass developed in membrane bioreactors (MBR) to degrade and sorb emerging micropollutants, biodegradation (kbiol) and sorption (ksor) kinetic constants as well as solid-liquid partition coefficients (Kd) of 13 selected pharmaceutical and personal care products (PPCPs) were determined with MBR heterotrophic biomass adding a pulse (100 ppb of each compound) and following the liquid and solid phase concentrations over time. The results obtained were compared to literature data referring to conventional activated sludge (CAS) systems. Two experiments were performed: one in the MBR itself and the second one in a batch reactor with the same type and concentration of biomass as in the MBR. Overall, both biodegradation and sorption coefficients were in the same range as previously reported by other studies in CAS systems, indicating that MBR biomass does not show better capabilities for the biological degradation and/or sorption of PPCPs compared to the biomass developed in CAS reactors. Therefore, the higher PPCPs removal efficiencies found in MBRs are explained by the high biomass concentrations obtained at the long sludge retention times at which this type of reactors are usually operated. PMID- 22773132 TI - Further characterization of ATP6V0A2-related autosomal recessive cutis laxa. AB - Autosomal recessive cutis laxa (ARCL) syndromes are phenotypically overlapping, but genetically heterogeneous disorders. Mutations in the ATP6V0A2 gene were found to underlie both, autosomal recessive cutis laxa type 2 (ARCL2), Debre type, and wrinkly skin syndrome (WSS). The ATP6V0A2 gene encodes the a2 subunit of the V-type H(+)-ATPase, playing a role in proton translocation, and possibly also in membrane fusion. Here, we describe a highly variable phenotype in 13 patients with ARCL2, including the oldest affected individual described so far, who showed strikingly progressive dysmorphic features and heterotopic calcifications. In these individuals we identified 17 ATP6V0A2 mutations, 14 of which are novel. Furthermore, we demonstrate a localization of ATP6V0A2 at the Golgi-apparatus and a loss of the mutated ATP6V0A2 protein in patients' dermal fibroblasts. Investigation of brefeldin A-induced Golgi collapse in dermal fibroblasts as well as in HeLa cells deficient for ATP6V0A2 revealed a delay, which was absent in cells deficient for the ARCL-associated proteins GORAB or PYCR1. Furthermore, fibroblasts from patients with ATP6V0A2 mutations displayed elevated TGF-beta signalling and increased TGF-beta1 levels in the supernatant. Our current findings expand the genetic and phenotypic spectrum and suggest that, besides the known glycosylation defect, alterations in trafficking and signalling processes are potential key events in the pathogenesis of ATP6V0A2-related ARCL. PMID- 22773133 TI - Low-temperature atmospheric plasma increases the expression of anti-aging genes of skin cells without causing cellular damages. AB - Efforts to employ various types of plasma in the field of skin care have increased consistently because it can regulate many biochemical reactions that are normally unaffected by light-based therapy. One method for skin rejuvenation adopted a high-temperature plasma generator to remove skin epithelial cells. In this case, the catalyzing effects of the plasma were rarely used due to the high temperature. Hence, the benefits of the plasma were not magnified. Recently, many types of low-temperature plasma devices have been developed for medical applications but their detailed functions and working mechanisms are unclear. The present study examined the effect of low-temperature microwave plasma on skin cells. Treatment with low-temperature plasma increased the expression of anti aging genes in skin cells, including collagen, fibronectin and vascular endothelial growth factor. Furthermore, the plasma treatment did not cause cell death, but only induced slight cell growth arrest at the G2 phase. Although the cells treated with low-temperature plasma showed moderate growth arrest, there were no signs of thermal or genetic damage of skin cells. Overall, this low temperature microwave plasma device induces the expressions of some anti-aging related genes in skin cells without causing damage. PMID- 22773134 TI - Can morphine interfere in the healing process during chronic stress? AB - Technological advances, constant pressure, increased qualified demand, and other daily activities present in modern society result in increasingly stressful living conditions for the population. In the short term, the release of stress related hormones can play a key role in the survival of an organism. However, it is well known that chronic exposure to cortisol can lead to many adverse effects. Several findings show immunological changes in response to chronic exposure to cortisol, in particular in skin integrity, which may interfere with the healing process. Morphine is an immunosuppressive drug, and when it is used chronically, it can lead to an increased incidence of infections and a delay in the healing process. The importance of opiates as analgesics in the medical setting is indisputable. However, there are a limited number of studies in this field. These investigations can provide further understanding of the mechanisms involved in the healing process in morphine-dependent individuals under chronic stress, which is a common condition in modern society. Furthermore, medical prescriptions of opiates are common among terminal patients, who frequently develop decubitus ulcers and bacterial infections. This review is aimed to provide a concise analysis of effects of morphine and stress on the healing process. PMID- 22773135 TI - A novel approach for evaluating the risk of health care failure modes. AB - Failure mode and effects analysis (FMEA) can be employed to reduce medical errors by identifying the risk ranking of the health care failure modes and taking priority action for safety improvement. The purpose of this paper is to propose a novel approach of data analysis. The approach is to integrate FMEA and a mathematical tool-Data envelopment analysis (DEA) with "slack-based measure" (SBM), in the field of data analysis. The risk indexes (severity, occurrence, and detection) of FMEA are viewed as multiple inputs of DEA. The practicality and usefulness of the proposed approach is illustrated by one case of health care. Being a systematic approach for improving the service quality of health care, the approach can offer quantitative corrective information of risk indexes that thereafter reduce failure possibility. For safety improvement, these new targets of the risk indexes could be used for management by objectives. But FMEA cannot provide quantitative corrective information of risk indexes. The novel approach can surely overcome this chief shortcoming of FMEA. After combining DEA SBM model with FMEA, the two goals-increase of patient safety, medical cost reduction-can be together achieved. PMID- 22773136 TI - Gemfibrozil pretreatment affecting antioxidant defense system and inflammatory, but not Nrf-2 signaling pathways resulted in female neuroprotection and male neurotoxicity in the rat models of global cerebral ischemia-reperfusion. AB - Two important pathophysiological mechanisms involved during cerebral ischemia are oxidative stress and inflammation. In pathological conditions such as brain ischemia the ability of free radicals production is greater than that of elimination by endogenous antioxidative systems, so brain is highly injured due to oxidation and neuroinflammation. Fibrates as peroxisome proliferator-activated receptor (PPAR)-alpha ligands, are reported to have antioxidant and anti inflammatory actions. In this study, gemfibrozil, a fibrate is investigated for its therapeutic potential against global cerebral ischemia-reperfusion (I/R) injury of male and female rats. This study particularly has focused on inflammatory and antioxidant signaling pathways, such as nuclear factor erythroid related factor (Nrf)-2, as well as the activity of some endogenous antioxidant agents. It was found that pretreatment of animals with gemfibrozil prior to I/R resulted in a sexually dimorphic outcome. Within females it proved to be protective, modulating inflammatory factors and inducing antioxidant defense system including superoxide dismutase (SOD), catalase, as well as glutathione level. However, Nrf-2 signaling pathway was not affected. It also decreased malondialdehyde level as an index of lipid peroxidation. In contrast, gemfibrozil pretreatment was toxic to males, enhancing the expression of inflammatory factors such as tumor necrosis factor-alpha, nuclear factor-kappaB, and cyclooxygenase-2, and decreasing Nrf-2 expression and SOD activity, leading to hippocampal neurodegeneration. Considering that gemfibrozil is a commonly used anti hyperlipidemic agent in clinic, undoubtedly more investigations are crucial to exactly unravel its sex-dependent neuroprotective/neurodegenerative potential. PMID- 22773139 TI - GFAJ-1 is an arsenate-resistant, phosphate-dependent organism. AB - The bacterial isolate GFAJ-1 has been proposed to substitute arsenic for phosphorus to sustain growth. We have shown that GFAJ-1 is able to grow at low phosphate concentrations (1.7 MUM), even in the presence of high concentrations of arsenate (40 mM), but lacks the ability to grow in phosphorus-depleted (<0.3 MUM), arsenate-containing medium. High-resolution mass spectrometry analyses revealed that phosphorylated central metabolites and phosphorylated nucleic acids predominated. A few arsenylated compounds, including C6 sugar arsenates, were detected in extracts of GFAJ-1, when GFAJ-1 was incubated with arsenate, but further experiments showed they formed abiotically. Inductively coupled plasma mass spectrometry confirmed the presence of phosphorus in nucleic acid extracts, while arsenic could not be detected and was below 1 per mil relative to phosphorus. Taken together, we conclude that GFAJ-1 is an arsenate-resistant, but still a phosphate-dependent, bacterium. PMID- 22773137 TI - Neural crest and olfactory system: new prospective. AB - Sensory neurons in vertebrates are derived from two embryonic transient cell sources: neural crest (NC) and ectodermal placodes. The placodes are thickenings of ectodermal tissue that are responsible for the formation of cranial ganglia as well as complex sensory organs that include the lens, inner ear, and olfactory epithelium. The NC cells have been indicated to arise at the edges of the neural plate/dorsal neural tube, from both the neural plate and the epidermis in response to reciprocal interactions Moury and Jacobson (Dev Biol 141:243-253, 1990). NC cells migrate throughout the organism and give rise to a multitude of cell types that include melanocytes, cartilage and connective tissue of the head, components of the cranial nerves, the dorsal root ganglia, and Schwann cells. The embryonic definition of these two transient populations and their relative contribution to the formation of sensory organs has been investigated and debated for several decades (Basch and Bronner-Fraser, Adv Exp Med Biol 589:24-31, 2006; Basch et al., Nature 441:218-222, 2006) review (Baker and Bronner-Fraser, Dev Biol 232:1-61, 2001). Historically, all placodes have been described as exclusively derived from non-neural ectodermal progenitors. Recent genetic fate mapping studies suggested a NC contribution to the olfactory placodes (OP) as well as the otic (auditory) placodes in rodents (Murdoch and Roskams, J Neurosci Off J Soc Neurosci 28:4271-4282, 2008; Murdoch et al., J Neurosci 30:9523-9532, 2010; Forni et al., J Neurosci Off J Soc Neurosci 31:6915-6927, 2011b; Freyer et al., Development 138:5403-5414, 2011; Katoh et al., Mol Brain 4:34, 2011). This review analyzes and discusses some recent developmental studies on the OP, placodal derivatives, and olfactory system. PMID- 22773140 TI - Absence of detectable arsenate in DNA from arsenate-grown GFAJ-1 cells. AB - A strain of Halomonas bacteria, GFAJ-1, has been claimed to be able to use arsenate as a nutrient when phosphate is limiting and to specifically incorporate arsenic into its DNA in place of phosphorus. However, we have found that arsenate does not contribute to growth of GFAJ-1 when phosphate is limiting and that DNA purified from cells grown with limiting phosphate and abundant arsenate does not exhibit the spontaneous hydrolysis expected of arsenate ester bonds. Furthermore, mass spectrometry showed that this DNA contains only trace amounts of free arsenate and no detectable covalently bound arsenate. PMID- 22773138 TI - Tauroursodeoxycholic acid prevents MPTP-induced dopaminergic cell death in a mouse model of Parkinson's disease. AB - Mitochondrial dysfunction and oxidative stress are implicated in the neurodegenerative process in Parkinson's disease (PD). Moreover, c-Jun N-terminal kinase (JNK) plays an important role in dopaminergic neuronal death in substantia nigra pars compacta. Tauroursodeoxycholic acid (TUDCA) acts as a mitochondrial stabilizer and anti-apoptotic agent in several models of neurodegenerative diseases. Here, we investigated the role of TUDCA in preventing 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration in a mouse model of PD. We evaluated whether TUDCA modulates MPTP-induced degeneration of dopaminergic neurons in the nigrostriatal axis, and if that can be explained by regulation of JNK phosphorylation, reactive oxygen species (ROS) production, glutathione S-transferase (GST) catalytic activation, and Akt signaling, using C57BL/6 glutathione S-transferase pi (GSTP) null mice. TUDCA efficiently protected against MPTP-induced dopaminergic degeneration. We have previously demonstrated that exacerbated JNK activation in GSTP null mice resulted in increased susceptibility to MPTP neurotoxicity. Interestingly, pre-treatment with TUDCA prevented MPTP-induced JNK phosphorylation in mouse midbrain and striatum. Moreover, the anti-oxidative role of TUDCA was demonstrated in vivo by impairment of ROS production in the presence of MPTP. Finally, results herein suggest that the survival pathway activated by TUDCA involves Akt signaling, including downstream Bad phosphorylation and NF-kappaB activation. We conclude that TUDCA is neuroprotective in an in vivo model of PD, acting mainly by modulation of JNK activity and cellular redox thresholds, together with activation of the Akt pro survival pathway. These results open new perspectives for the pharmacological use of TUDCA, as a modulator of neurodegeneration in PD. PMID- 22773142 TI - Don't let obese patients be discharged with tachycardia after sleeve gastrectomy. PMID- 22773143 TI - Reducing health risk assigned to organic emissions from a chemical weapons incinerator. AB - Organic emissions from a chemical weapons incinerator have been characterized with an improved set of analytical methods to reduce the human health risk assigned to operations of the facility. A gas chromatography/mass selective detection method with substantially reduced detection limits has been used in conjunction with scanning electron microscopy/energy dispersive X-ray spectrometry and Fourier transform infrared microscopy to improve the speciation of semi-volatile and non-volatile organics emitted from the incinerator. The reduced detection limits have allowed a significant reduction in the assumed polycyclic aromatic hydrocarbon (PAH) and aminobiphenyl (ABP) emission rates used as inputs to the human health risk assessment for the incinerator. A mean factor of 17 decrease in assigned human health risk is realized for six common local exposure scenarios as a result of the reduced PAH and ABP detection limits. PMID- 22773141 TI - Increased plasma magnesium concentrations 3 years after biliopancreatic diversion with duodenal switch. AB - BACKGROUND: Biliopancreatic diversion with duodenal switch, BPD-DS, is a surgical procedure for treatment of super obese patients. It renders very good weight results and it strongly reduces the incidence of type 2 diabetes. One important mechanism of weight reduction after BPD-DS is malabsorption. Hypomagnesemia is an established cardiovascular risk factor. While it is well-known that magnesium levels decline after jejuno-ileal bypass and increase after gastric bypass surgery, information on how magnesium status is affected by BPD-DS is scant. The aim of the present study was to evaluate plasma magnesium concentrations (P-Mg) after BPD-DS. METHODS: Thirty-one patients, all Caucasians (9 diabetics, 12 men, age 38 +/- 8 years, weight 159 +/- 22 kg, body mass index (BMI) 53.9 +/- 5.2 kg/m(2)) underwent BPD-DS. We evaluated weight, glycated hemoglobin levels (HbA1c) and P-Mg preoperatively as well as at 1 and 3 years after surgery. All subjects were treated with vitamin and mineral substitution after surgery, including 100 mg of magnesium salt. P-Mg was analyzed with respect to changes over time, correlation to BMI and HbA1c levels before and 3 years after surgery. RESULTS: The plasma magnesium concentrations increased by 15 % from 0.77 +/- 0.07 to 0.88 +/- 0.09 mmol/l over 3 years (p < 0.001). The weight loss was 71 +/- 25 kg. No patient had diabetes at follow-up. No correlations between P-Mg and BMI or HbA1c were seen. CONCLUSIONS: Although exerting much of its weight-reducing effect by a malabsorptive mechanism, BPD-DS yields a rise in P-Mg 3 years postoperatively, possibly contributing to the improved metabolic state after this operation. PMID- 22773144 TI - Optimal water and waste-load allocations in rivers using a fuzzy transformation technique: a case study. AB - In this paper, a new methodology is developed for integrated allocation of water and waste-loads in river basins utilizing a fuzzy transformation method (FTM). The fuzzy transformation method is used to incorporate the existing uncertainties in model inputs. In the proposed methodology, the FTM, as a simulation model, is utilized in an optimization framework for constructing a fuzzy water and waste loads allocation model. In addition, economic as well as environmental impacts of water allocation to different water users are considered. For equitable water and waste load allocation, all possible coalition of water users are considered and total benefit of each coalition, which is a fuzzy number, is reallocated to water users who are participating in the coalition. The fuzzy cost savings are reallocated using a fuzzy nucleolus cooperative game and the FTM. As a case study, the Dez River system in south-west of Iran is modeled and analyzed using the methodology developed here. The results show the effectiveness of the methodology in optimal water and waste-loads allocations under uncertainty. PMID- 22773145 TI - Bark removal and population structure of Taxus wallichiana Zucc. in a temperate mixed conifer forest of western Himalaya. AB - Taxus wallichiana Zucc. (Himalayan yew) represents one of the most threatened medicinal tree species of the Himalayan region. Heavy exploitation of its bark and leaves for taxol(r) has resulted in decline in its population. Generating quantitative information on Himalayan yew has therefore been stressed. The present paper provides information on the population and bark removal of Himalayan yew from one of the interior areas of Himalaya. Total count and quadrat method were deployed to generate quantitative information on its population while bark removal was estimated based on depth and extent of bark removed. After analyzing the existing information and the results of the study, a rapid vulnerability assessment (RVA) of the species was carried out. Taxus reported a density of 72 individuals/ha and was present as an under canopy of Picea smithiana. Complete stripping of bark was observed in 11 % of the Taxus population which amounted to ca. 18,152.86 cm(3) of bark removed. The age class distribution showed complete absence of seedlings and saplings. RVA scores also reported higher values (26) thereby pointing toward the high vulnerability of this species. Across its entire distributional range, Taxus population is under severe pressure. It is high time when few patches of Taxus are demarcated as Medicinal Plant Conservation Areas, and detailed studies on its autecology are initiated. PMID- 22773146 TI - Joint ecotoxicology of cadmium and metsulfuron-methyl in wheat (Triticum aestivum). AB - Herbicide is indispensable for crop production. However, substantial usage of herbicide has led to its increasing accumulation in soils and crops. In addition, cadmium has become one of the widely occurring contaminants in soils due to its significant release into environment via anthropogenic activities. In this study, ecotoxicological investigations were made by exposing the food crop wheat to joint contaminations of Cd and metsulfuron-methyl, a sulfonylurea herbicide. We analyzed growth and physiological and molecular responses in wheat exposed to 0.5 mg kg(-1) Cd and 0.02 mg kg(-1) metsulfuron-methyl (MSM). Soils contaminated with Cd and MSM complex caused significantly detrimental effect on wheat growth and physiological process. Combinative treatments with Cd and MSM damage more severely the plant cells as compared with Cd or MSM treatment alone. Compared with the growth parameter, the biochemical and molecular responses of wheat appeared more pronounced to Cd and MSM complex. Furthermore, compared with control, wheat plants exposed to Cd + MSM generated more O(2-.)and H2O2, both of which were shown to be the cause of enhanced activity of several antioxidant enzymes. Native polyacrylamide gel eletrophoresis and molecular response analyses were performed to validate the results indicated above. Our results indicated that joint contamination with Cd and MSM was more toxic to wheat than a single contamination. These sensitive biological parameters can be used as biomarkers monitoring the ecotoxicological process in plants. PMID- 22773148 TI - Toxicity assessment for petroleum-contaminated soil using terrestrial invertebrates and plant bioassays. AB - The assessment of soil quality after a chemical or oil spill and/or remediation effort may be measured by evaluating the toxicity of soil organisms. To enhance our understanding of the soil quality resulting from laboratory and oil field spill remediation, we assessed toxicity levels by using earthworms and springtails testing and plant growth experiments. Total petroleum hydrocarbons (TPH)-contaminated soil samples were collected from an oilfield in Sfax, Tunisia. Two types of bioassays were performed. The first assessed the toxicity of spiked crude oil (API gravity 32) in Organization for Economic Co-operation and Development artificial soil. The second evaluated the habitat function through the avoidance responses of earthworms and springtails and the ability of Avena sativa to grow in TPH-contaminated soils diluted with farmland soil. The EC50 of petroleum-contaminated soil for earthworms was 644 mg of TPH/kg of soil at 14 days, with 67 % of the earthworms dying after 14 days when the TPH content reached 1,000 mg/kg. The average germination rate, calculated 8 days after sowing, varied between 64 and 74 % in low contaminated soils and less than 50 % in highly contaminated soils. PMID- 22773147 TI - Effect of elevated CO2 on degradation of azoxystrobin and soil microbial activity in rice soil. AB - An experiment was conducted in open-top chambers (OTC) to study the effect of elevated CO2 (580 +/- 20 MUmol mol(-1)) on azoxystrobin degradation and soil microbial activities. Results indicated that elevated CO2 did not have any significant effect on the persistence of azoxystrobin in rice-planted soil. The half-life values for the azoxystrobin in rice soils were 20.3 days in control (rice grown at ambient CO2 outdoors), 19.3 days in rice grown under ambient CO2 atmosphere in OTC, and 17.5 days in rice grown under elevated CO2 atmosphere in OTC. Azoxystrobin acid was recovered as the only metabolite of azoxystrobin, but it did not accumulate in the soil/water and was further metabolized. Elevated CO2 enhanced soil microbial biomass (MBC) and alkaline phosphatase activity of soil. Compared with rice grown at ambient CO2 (both outdoors and in OTC), the soil MBC at elevated CO2 increased by twofold. Elevated CO2 did not affect dehydrogenase, fluorescein diacetate, and acid phosphatase activity. Azoxystrobin application to soils, both ambient and elevated CO2, inhibited alkaline phosphates activity, while no effect was observed on other enzymes. Slight increase (1.8-2 degrees C) in temperature inside OTC did not affect microbial parameters, as similar activities were recorded in rice grown outdoors and in OTC at ambient CO2. Higher MBC in soil at elevated CO2 could be attributed to increased carbon availability in the rhizosphere via plant metabolism and root secretion; however, it did not significantly increase azoxystrobin degradation, suggesting that pesticide degradation was not the result of soil MBC alone. Study suggested that increased CO2 levels following global warming might not adversely affect azoxystrobin degradation. However, global warming is a continuous and cumulative process, therefore, long-term studies are necessary to get more realistic assessment of global warming on fate of pesticide. PMID- 22773149 TI - Comparison of the diagnostic performances of two protocols of hand perfusion scintigraphy for Raynaud's phenomenon. AB - OBJECTIVE: The aim of this study was to compare the diagnostic performances of two hand perfusion scintigraphy protocols for diagnosing Raynaud's phenomenon (RP). METHODS: We enrolled 130 patients who underwent hand perfusion scintigraphy for suspected RP and 40 normal controls. Of these, 66 patients (group A) and 25 normal controls underwent 99mTc-methylene diphosphonate hand perfusion scintigraphy without one-hand chilling, and the finger-to-palm ratio (FPR) was calculated. The remaining 64 patients (group B) and 15 normal controls underwent 99mTc-methylene diphosphonate hand perfusion scintigraphy with one-hand chilling, and three parameters (the chilled-to-ambient hand ratios of the first peak height, initial slope, and blood pool uptake) were calculated. RESULTS: Forty eight and 47 patients were clinically diagnosed with RP in groups A and B, respectively. In group A, patients with RP had significantly lower FPRs compared with those without RP, and the receiver operating characteristic curve analysis showed that an FPR of 0.51 was the best cutoff value for diagnosing RP, with a sensitivity of 63% and a specificity of 83%. In group B, the three aforementioned parameters differed significantly (lower or higher) between patients with and without RP. The receiver operating characteristic curve analysis provided highly sensitive and specific results for all three parameters. The initial slope ratio showed the highest sensitivity of 87% and a specificity of 88% when using cutoff values of 0.78 and 1.25. CONCLUSION: Although both protocols for hand perfusion scintigraphy showed high specificity for diagnosing RP, the protocol with one hand chilling showed higher diagnostic ability compared with that without one hand chilling. PMID- 22773150 TI - Correlation between serum 25-hydroxyvitamin D concentrations and regional cerebral blood flow in degenerative dementia. AB - BACKGROUND: Chronic low serum vitamin D concentrations are common among the elderly. Recent studies have suggested that its metabolite, 25-hydroxyvitamin D (25-OHD), might be important for preserving cognitive functions through specific brain protective effects. However, this hypothesis is still under discussion. The aim of this study was to assess the correlation between serum 25-OHD concentrations and regional cerebral blood flow in neurodegenerative diseases such as Alzheimer's disease (AD) and dementia of Lewy bodies (DLB). PATIENTS AND METHODS: Radionuclide brain single-photon emission computed tomography/computed tomography (SPECT/CT) images and 25-OHD dosage in noninstitutionalized patients were obtained within 14 days. SPECT/CT examination was carried out using technetium-99m-ethyl cysteinate dimer in 20 consecutive patients (12 AD and eight DLB). Reconstructed images were spatially normalized using Statistical Parametric Mapping version 5 software to a default SPECT template. Voxel-based multiple regression correlation analyses, with age and mini mental state examination scores as confounding factors, were carried out. Findings were considered significant for a threshold P-value less than 0.01 (corrected at cluster level). RESULTS: A positive correlation was found between 25-OHD concentrations and regional cerebral blood flow in the left precuneus cortex (Talairach coordinates: -14, -42, 63) in AD patients. No correlation was detected in DLB patients. CONCLUSION: The results of this study confirm the relationship between 25-OHD concentrations and AD and therefore underline the hypothesis of a potential neuroprotective effect against brain degeneration. These encouraging findings need to be confirmed by larger prospective correlation series. PMID- 22773151 TI - Positron emission tomography radiopharmaceutical studies in humans: a guide to regulations for academic researchers. AB - All clinical trials are covered by a series of regulations that seek to protect the rights, safety and welfare of participating patients. The regulations covering PET studies are especially complex to interpret because of the specialized nature of the language of the regulations and of PET studies themselves. It is often unclear whether the application demands that the radiotracer used be treated as an investigational medical product. This paper is intended to act as a general guide for UK researchers planning to perform PET research in humans by clarifying key aspects of the regulations that may affect the study and/or the radiopharmaceutical manufacturing process, providing links to useful information sources, introducing the concept of a UK Medicines and Healthcare products Regulatory Agency (MHRA) PET expert panel and outlining the value of sharing investigational medical product dossiers. PMID- 22773152 TI - Antibodies against human cytomegalovirus late protein UL94 in the pathogenesis of scleroderma-like skin lesions in chronic graft-versus-host disease. AB - Human cytomegalovirus (hCMV) infection and its reactivation correlate both with the increased risk and with the worsening of graft-versus-host disease (GVHD). Because scleroderma-like skin lesions can occur in chronic GVHD (cGVHD) in allogeneic stem-cell transplant (HCT) patients and hCMV is relevant in the pathogenesis of systemic sclerosis (SSc), we evaluated the possible pathogenetic link between hCMV and skin cGVHD. Plasma from 18 HCT patients was tested for anti UL94 and/or anti-NAG-2 antibodies, identified in SSc patients, by direct ELISA assays. Both donors and recipients were anti-hCMV IgG positive, without autoimmune diseases. Patients' purified anti-UL94 and anti-NAG-2 IgG binding to human umbilical endothelial cells (HUVECs) and fibroblasts was performed by FACS analysis and ELISA test. HUVECs apoptosis and fibroblasts proliferation induced by patients' anti-NAG-2 antibodies were measured by DNA fragmentation and cell viability, respectively. About 11/18 patients developed cGVHD and all of them showed skin involvement, ranging from diffuse SSc-like lesions to limited erythema. Eight of eleven cGVHD patients were positive for anti-UL94 and/or anti NAG-2 antibodies. Remarkably, 4/5 patients who developed diffuse or limited SSc like lesions had antibodies directed against both UL94 and NAG-2; their anti-NAG 2 IgG-bound HUVECs and fibroblasts induce both endothelial cell apoptosis and fibroblasts proliferation, similar to that induced by purified anti-UL94 and anti NAG-2 antibodies obtained from SSc patients. In conclusion, our data suggest a pathogenetic link between hCMV infection and scleroderma-like skin cGVHD in HCT patients through a mechanism of molecular mimicry between UL94 viral protein and NAG-2 molecule, as observed in patients with SSc. PMID- 22773153 TI - IRF-2 regulates B-cell proliferation and antibody production through distinct mechanisms. AB - Interferon regulatory factor (IRF)-2 is a transcription factor involved in type I (IFN- alpha/beta) signaling. It has been reported that IRF-2 deficiency results in various immune dysfunctions. However, the role of IRF-2 in B-cell functions needs to be elucidated. Unlike wild-type (WT) B cells, IRF-2(-/-) B2 cells were refractory to anti-IgM, but not LPS. Such a defect in proliferation was dependent on IFN- alpha/beta receptor (IFNAR). Marginal zone B cells increased in the proportion relative to B2 cells in IRF-2(-/-) mice produced IgM normally to LPS stimulation. However, IRF-2(-/-) B2 cells were defective in IgM production in an IFNAR-independent manner, although both B-cell subsets differentiated phenotypically to plasma cells at elevated efficiencies. Class switch recombination of IRF-2(-/-) B2 cells by LPS plus IL-4 was also impaired. Their reduced IgM production was conceivably due to an inefficient up-regulation of Blimp-1. Consistent with these in vitro observations, specific antibody production in vivo to a T-dependent antigen by B2 cells was severely impaired in IRF-2(-/- )mice. However, a low, but significant, level of IgG was detected at a late time point, and this IgG exhibited comparable binding affinity to that in WT mice. Follicular helper T-cell development and germinal center formation were normal. A similar tendency was observed when u chain(-/-) mice were reconstituted with IRF-2(-/- )B cells. These results revealed a multi-faceted role of IRF-2 in the function of B cells, particularly B2 cells, through regulating proliferation in an IFNAR-dependent manner and antibody production via up-regulation of Blimp 1. PMID- 22773154 TI - The 87%. PMID- 22773155 TI - Real-time monitoring of strand-displacement DNA amplification by a contactless electrochemical microsystem using interdigitated electrodes. AB - This paper reports the design and implementation of a contactless conductivity detection system which combines a thermal control cell, a data processing system and an electrochemical (EC) cell for label-free isothermal nucleic acid amplification and real-time monitoring. The EC cell consists of a microchamber and interdigitated electrodes as the contactless conductivity biosensor with a cover slip as insulation. In our work, contactless EC measurements, the effects of trehalose on amplification, and chip surface treatment are investigated. With the superior performance of the biosensor, the device can detect the amount of pure DNA at concentrations less than 0.1 pg MUl(-1). The EC cell, integrated with a heater and a temperature sensor, has successfully implemented nicking-based strand-displacement amplification at an initial concentration of 2.5 MUM and the yields are monitored directly (dismissing the use of probes or labels) on-line. This contactless detector carries important advantages: high anti-interference capability, long detector life, high reusability and low cost. In addition, the small size, low power consumption and portability of the detection cell give the system the potential to be highly integrated for use in field service and point of care applications. PMID- 22773156 TI - Estimation of tumour mass in patients with differentiated thyroid carcinoma using serum thyroglobulin. AB - Serum thyroglobulin (Tg) is a reliable tumour marker in follow-up of patients with differentiated thyroid carcinoma (DTC). A positive correlation between Tg level and tumour mass was recently observed, but no attempts were made to derive a numerical relation. The aim of this study was to derive a numerical relationship between serum Tg level and tumour mass that allows optimizing the diagnostic procedures. PATIENTS, METHOD: 78 DTC patients with tumour lesions in either 124I-NaI or 18F-FDG PET/CT were included. For each patient, the total tumour mass was determined functionally in iodine- and FDG-positive lesions as well as morphologically in only CT-positive lesions. The serum Tg level was measured under TSH stimulation prior to imaging. Regression analyses were performed to derive an approach for estimation of the total tumour mass based on Tg levels. RESULTS: A positive correlation of serum Tg and tumour mass was confirmed and a mathematical expression was given to estimate the tumour mass along with its 95% confidence interval using only the serum Tg level. The results demonstrated that the range of predicted tumour mass was higher per serum Tg unit for iodine-positive lesions than for FDG-positive tumour lesions and was higher for follicular than for papillary thyroid carcinoma. CONCLUSION: This study provides an approach to estimate the tumour mass and its 95% confidence intervals in DTC patients using the serum Tg level. The range of the estimated tumour mass for a given Tg level is rather large, and therefore, the approach is of limited value in clinical application. PMID- 22773157 TI - Palladium-catalyzed esterification of aryl halides using aryl formates without the use of external carbon monoxide. AB - Aryl formates are efficient carbon monoxide sources in palladium-catalyzed esterification of aryl halides. The carbonylation readily proceeds at ambient pressure without the use of external carbon monoxide to afford the corresponding esters in high yields. PMID- 22773158 TI - Oncology in vivo data integration for hypothesis generation. AB - AstraZeneca’s Oncology in vivo data integration platform brings multidimensional data from animal model efficacy, pharmacokinetic and pharmacodynamic data to animal model profiling data and public in vivo studies. Using this platform, scientists can cluster model efficacy and model profiling data together, quickly identify responder profiles and correlate molecular characteristics to pharmacological response. Through meta-analysis, scientists can compare pharmacology between single and combination treatments, between different drug scheduling and administration routes. PMID- 22773159 TI - Knowledge enrichment analysis for human tissue-specific genes uncover new biological insights. AB - The expression and regulation of genes in different tissues are fundamental questions to be answered in biology. Knowledge enrichment analysis for tissue specific (TS) and housekeeping (HK) genes may help identify their roles in biological process or diseases and gain new biological insights. In this paper, we performed the knowledge enrichment analysis for 17,343 genes in 84 human tissues using Gene Set Enrichment Analysis (GSEA) and Hypergeometric Analysis (HA) against three biological ontologies: Gene Ontology (GO), KEGG pathways and Disease Ontology (DO) respectively. The analyses results demonstrated that the functions of most gene groups are consistent with their tissue origins. Meanwhile three interesting new associations for HK genes and the skeletal muscle tissue genes are found. Firstly, Hypergeometric analysis against KEGG database for HK genes disclosed that three disease terms (Parkinson's disease, Huntington's disease, Alzheimer's disease) are intensively enriched. Secondly, Hypergeometric analysis against the KEGG database for Skeletal Muscle tissue genes shows that two cardiac diseases of "Hypertrophic cardiomyopathy (HCM)" and "Arrhythmogenic right ventricular cardiomyopathy (ARVC)" are heavily enriched, which are also considered as no relationship with skeletal functions. Thirdly, "Prostate cancer" is intensively enriched in Hypergeometric analysis against the disease ontology (DO) for the Skeletal Muscle tissue genes, which is a much unexpected phenomenon. PMID- 22773160 TI - Formation of lipid bilayers inside microfluidic channel array for monitoring membrane-embedded nanopores of phi29 DNA packaging nanomotor. AB - An efficient method to form lipid bilayers inside an array of microfluidic channels has been developed and applied to monitor the membrane-embedded phi29 DNA packaging motor with an electrochemical characterization on a lab-on-a-chip (LOC) platform. A push-pull junction capturing approach was applied to confine a small amount of the lipid solution inside a microchannel. The selective permeability between solvents and water in PDMS was utilized to extract the solvent from the lipid solution, resulting in a self-formation of the lipid bilayer in the microchannel array. Each microchannel was independently connected to a silver/silver chloride (Ag/AgCl) electrode array, leading to a high throughput monitoring of the nanopore insertion in the formed lipid bilayers. The formation of multiple lipid bilayers inside an array of microchannels and the simultaneous electrical and optical monitoring of multiple bilayer provides an efficient LOC platform for the further development of single phi29 motor pore sensing and high throughput single pore dsDNA sequencing. PMID- 22773161 TI - Monitoring the endocytosis of magnetic nanoparticles by cells using permanent micro-flux sources. AB - Trapping of cells is essential to perform basic handling operations in cell-based microsystems, such as media exchange, concentration, cell isolation and cell sorting. Cell trapping by magnetophoresis typically requires cell labeling with magnetic nanoparticles. Here we report on endocytotic uptake of 100 nm magnetic nanoparticles by Human Embryonic Kidney 293 cells. The attraction of labeled cells by micro-magnet arrays characterised by very high magnetic field gradients (<=106 T/m) was studied as a function of labeling conditions (nanoparticle concentration in the extracellular medium, incubation time). The threshold incubation conditions for effective magnetophoretic trapping were established. This simple technique may be exploited to minimise the quantity of magnetic nanoparticles needed for efficient cell trapping, thus reducing stress or nanoparticle-mediated toxicity. Nanoparticle internalization into cells was confirmed using both confocal and Transmission Electron Microscopy (TEM). PMID- 22773162 TI - Informed consent in clinical practice and literature overview. AB - Informed consent is a legal requirement to be fulfilled before any procedure is carried out in clinical practice. It has wide ramification and different interpretations in the present healthcare system. Free and informed consent is required for medical treatments and procedures, except in an emergency situation when informed consent cannot be obtained and there is no indication that a reasonable patient would refuse consent to treatment. Increasing litigations and other ethical considerations have prompted us to review this subject with a review of literature on subject and inferences by different experts in this field. PMID- 22773163 TI - Cooperative self-assembly: producing synthetic polymers with precise and concise primary structures. AB - The quest to construct mechanically interlocked polymers, which present precise monodisperse primary structures that are produced both consistently and with high efficiencies, has been a daunting goal for synthetic chemists for many years. Our ability to realise this goal has been limited, until recently, by the need to develop synthetic strategies that can direct the formation of the desired covalent bonds in a precise and concise fashion while avoiding the formation of unwanted kinetic by-products. The challenge, however, is a timely and welcome one, as a consequence of, primarily, the potential for mechanically interlocked polymers to act as dynamic (noncovalent) yet robust (covalent) new materials for a wide array of applications. One such strategy which has been employed widely in recent years to address this issue, known as Dynamic Covalent Chemistry (DCC), is a strategy in which reactions operate under equilibrium and so offer elements of "proof-reading" and "error-checking" to the bond forming and breaking processes such that the final product distribution always reflects the thermodynamically most favourable compound. By coupling DCC with template-directed protocols, which utilise multiple weak noncovalent interactions to pre-organise and self-assemble simpler small molecular precursors into their desired geometries prior to covalent bond formation, we are able to produce compounds with highly symmetric, robust and complex topologies that are otherwise simply unobtainable by more traditional methods. Harnessing these strategies in an iterative, step-wise fashion brings us ever so much closer towards perfecting the controlled synthesis of high order main-chain mechanically interlocked polymers. This tutorial review focuses (i) on the development of DCC-namely, the formation of dynamic imine bonds-used in conjunction with template-directed protocols to afford a variety of mechanically interlocked molecules (MIMs) and ultimately (ii) on the synthesis of highly ordered poly[n]rotaxanes with high conversion efficiencies. PMID- 22773164 TI - From in vitro EC50 to in vivo dose-response for antiretrovirals using an HIV disease model. Part II: application to drug development. AB - The purpose of this research was to qualify a previously derived quantitative model-based framework that proposed an in vitro-in vivo linkage to predict the dose-response relationship of an antiretroviral (ARV) new molecular entity (NME) in a monotherapy trial. Human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) data from monotherapy trials in ARV naive/experienced HIV-infected subjects for eight drugs (i.e. application case, a representative drug for a given class used for external validation) across four distinct classes of ARV agents (co receptor antagonists; non-nucleoside reverse transcriptase inhibitors; nucleotide reverse transcriptase inhibitors; and integrase strand transfer inhibitors) were obtained. Using the in vitro EC50 (protein binding corrected) and a class specific scaling factor (SF), the in vivo IC50 was calculated for each drug. The integrated pharmacokinetic (PK)-pharmacodynamic (PD) disease model used the predicted in vivo IC50 to simulate the HIV-1 RNA-time profiles for dosing regimens that were studied in the monotherapy trials for each drug. The simulated HIV-1 RNA time profiles were then compared to the observed data. The simulated HIV-1 RNA-time profiles matched well with those observed in the monotherapy trials except for one drug in the INSTIs class. The derived SF represents a useful in vitro-in vivo linkage to predict the dose-response relationship for a NME using in vitro data. The mechanistic PK-PD disease model-based framework is useful to assist the dose selection for monotherapy trials and comparator modeling approaches. PMID- 22773165 TI - D2-receptor occupancy measurement of JNJ-37822681, a novel fast off-rate D2 receptor antagonist, in healthy subjects using positron emission tomography: single dose versus steady state and dose selection. AB - RATIONALE: JNJ-37822681 is a highly selective, fast dissociating dopamine D2 receptor antagonist being developed for the treatment of schizophrenia. A single dose [11C]raclopride positron emission tomography (PET) imaging study had yielded an estimated clinical dose range. Receptor occupancy at steady state was explored to test the validity of the single-dose estimates during chronic treatment. OBJECTIVES: The aims of this study are to characterize single and multiple dose pharmacokinetics and obtain striatal D2-receptor occupancies to predict doses for efficacy studies and assess the safety and tolerability of JNJ-37822681. METHODS: An open-label single- and multiple-dose study with 10 mg JNJ-37822681 (twice daily for 13 doses) was performed in 12 healthy men. Twenty [11C]raclopride PET scans (up to 60 h after the last dose) from 11 subjects were used to estimate D2 receptor occupancy. A direct effect O (max) model was applied to explore the relationship between JNJ-37822681 plasma concentration and striatal D2-receptor occupancy. RESULTS: Steady state was reached after 4-5 days of twice daily dosing. JNJ-37822681 plasma concentrations of 3.17 to 63.0 ng/mL resulted in D2 occupancies of 0 % to 62 %. The concentration leading to 50 % occupancy was 18.5 ng/mL (coefficient of variation 3.9 %) after single dose and 26.0 ng/mL (8.2 %) at steady state. JNJ-37822681 was well tolerated. CONCLUSIONS: Receptor occupancy after single dose and at steady state differed for JNJ-37822681 and the robustness of the estimates at steady state will be tested in phase 2 studies. Dose predictions indicated that 10, 20, and 30 mg JNJ-37822681 twice daily could be suitable for these studies. PMID- 22773166 TI - The incidence and relevance of prostate cancer in radical cystoprostatectomy specimens. AB - PURPOSE: To review the incidence, histopathological features and clinical outcomes of patients with incidental prostate cancer (CaP) found in cystoprostatectomy specimens (CP) excised for bladder cancer and to determine whether these prostate cancers could affect the follow-up strategy. PATIENTS AND METHODS: We retrospectively reviewed the records of 110 patients who underwent CP for bladder cancer (1998-2011) at our institution. CaP grade, stage, volume and surgical margin status were recorded. Prostatic involvement by bladder tumour or carcinoma in situ (CIS) was studied. Pre-operative prostate assessment and follow up in those diagnosed with incidental CaP were analysed. RESULTS: Incidental CaP was identified in 35 patients (32.5%), 4 with prostatic PIN alone and 2 patients with diagnoses of CaP prior to cystectomy were excluded from study. Of the CaP cases, 28.5% had clinically significant disease: 5 with Gleason score 7, 2 with Gleason score 9, who also had extracapsular invasion of tumour, and three with positive surgical margins. All patients were pN0 for CaP. Of the 108 patients, 16.5% had prostatic urethral involvement with CIS or TCC. In the subgroup of patients with the incidentally diagnosed CaP who developed local recurrence of bladder tumour and/or metastatic disease, none originated from their CaP. CONCLUSION: The majority of incidental CaP in CP specimens are organ confined and do not influence oncological outcome. The prognosis of such patients is primarily determined by bladder cancer. Our findings support previous reports and autopsy studies elsewhere. PMID- 22773167 TI - Reprogramming: so simple, so complex. PMID- 22773169 TI - Human homogamy in facial characteristics: does a sexual-imprinting-like mechanism play a role? AB - Human homogamy may be caused in part by individuals' preference for phenotypic similarities. Two types of preference can result in homogamy: individuals may prefer someone who is similar to themselves (self-referent phenotype matching) or to their parents (a sexual-imprinting-like mechanism). In order to examine these possibilities, we compare faces of couples and their family members in two ways. First, "perceived" similarity between a pair of faces is quantified as similarity ratings given to the pair. Second, "physical" similarity between two groups of faces is evaluated on the basis of correlations in principal component scores generated from facial measurements. Our results demonstrate a tendency to homogamy in facial characteristics and suggest that the tendency is due primarily to self-referent phenotype matching. Nevertheless, the presence of a sexual imprinting-like effect is also partially indicated: whether individuals are involved in facial homogamy may be affected by their relationship with their parents during childhood. PMID- 22773170 TI - GIA 2011: Genomics in Aquaculture 2011 Symposium. PMID- 22773171 TI - Multimodal imaging in the diagnosis of isolated left ventricular noncompaction. AB - Left ventricular noncompaction (LNVC), first described in 1984, is a rare congenital cardiomyopathy that is thought to be caused by arrest of normal embryogenesis of the endocardium and the myocardium, and characterized by multiple prominent trabeculations with deep intertrabecular recesses. LVNC can be associated with other congenital cardiac abnormalities such as atrial septal defect and ventricular septal defect, but it can occur in isolation. The clinical manifestations of the disease are variable, ranging from no symptoms to signs of heart failure, systemic emboli, and ventricular arrhythmias. The diagnosis is established by two dimensional echocardiography or magnetic resonance imaging. We report the case of a 44-year-old man with LVNC and discuss the role of multimodal imaging in the diagnosis and assessment of the disease. PMID- 22773172 TI - [Dehiscence of an aortic valve with consecutive high grade aortic insufficiency and cardiac shock. A rare complication of prosthetic valve endocarditis]. PMID- 22773174 TI - A novel structured bioreactor for solid-state fermentation. AB - A novel patented solid-state bioreactor (251 L) with honeycomb loading device was designed and its performance was tested. First, this apparatus gave a 66.87 % of calculated loading coefficient (volume ratio), which was almost twofold compared with conventional fermenters. Next, considering the crucial effect of heat transfer on bed loading and microbial growth, the performance was validated by temperature variance during fermentation and spore viability of Bacillus cereus DM423. Air pressure pulsation or external water jacket was used to control temperature; the maximal temperature variation was 7.7 versus 19.8 degrees C, respectively during fermentation. The difference was mainly due to the continuous gas phase characterized by solid-state fermentation (SSF). The average living spores of (1.50 +/- 0.07) * 10(11) cfu/g at 40 h obtained from the device was higher than (0.70 +/- 0.03) * 10(11) cfu/g from flask at 48 h. The results indicated that this new loading bioreactor with air pressure pulsation could be a good prospect for industrialization of SSF employing bacterial cultures. PMID- 22773173 TI - Clinical correlation and molecular evaluation confirm that the MLH1 p.Arg182Gly (c.544A>G) mutation is pathogenic and causes Lynch syndrome. AB - Approximately 25 % of mismatch repair (MMR) variants are exonic nucleotide substitutions. Some result in the substitution of one amino acid for another in the protein sequence, so-called missense variants, while others are silent. The interpretation of the effect of missense and silent variants as deleterious or neutral is challenging. Pre-symptomatic testing for clinical use is not recommended for relatives of individuals with variants classified as 'of uncertain significance'. These relatives, including non-carriers, are considered at high-risk as long as the contribution of the variant to disease causation cannot be determined. This results in continuing anxiety, and the application of potentially unnecessary screening and prophylactic interventions. We encountered a large Irish Lynch syndrome kindred that carries the c.544A>G (p.Arg182Gly) alteration in the MLH1 gene and we undertook to study the variant. The clinical significance of the variant remains unresolved in the literature. Data are presented on cancer incidence within five kindreds with the same germline missense variant in the MLH1 MMR gene. Extensive testing of relevant family members in one kindred, a review of the literature, review of online MMR mutation databases and use of in silico phenotype prediction tools were undertaken to study the significance of this variant. Clinical, histological, immunohistochemical and molecular evidence from these families and other independent clinical and scientific evidence indicates that the MLH1 p.Arg182Gly (c.544A>G) change causes Lynch syndrome and supports reclassification of the variant as pathogenic. PMID- 22773175 TI - A novel membrane-based process to isolate peroxidase from horseradish roots: optimization of operating parameters. AB - The optimization of operating parameters for the isolation of peroxidase from horseradish (Armoracia rusticana) roots with ultrafiltration (UF) technology was systemically studied. The effects of UF operating conditions on the transmission of proteins were quantified using the parameter scanning UF. These conditions included solution pH, ionic strength, stirring speed and permeate flux. Under optimized conditions, the purity of horseradish peroxidase (HRP) obtained was greater than 84 % after a two-stage UF process and the recovery of HRP from the feedstock was close to 90 %. The resulting peroxidase product was then analysed by isoelectric focusing, SDS-PAGE and circular dichroism, to confirm its isoelectric point, molecular weight and molecular secondary structure. The effects of calcium ion on HRP specific activities were also experimentally determined. PMID- 22773176 TI - Aging and cone dark adaptation. AB - PURPOSE: Following exposure to a bright light that bleaches a significant portion of photopigment, the eyes take several minutes to regain sensitivity. This slow process, known as dark adaptation, is impaired in patients with age-related macular degeneration and is an important candidate biomarker for this disease. The aim of this study was to evaluate the effect of age on cone dark adaptation. METHODS: Data were obtained from 41 healthy adults aged between 20 and 83 years. Pupils were dilated and 96% of cone photopigment was "bleached," before threshold was monitored continuously for 5 min in the dark, using a 4 degrees diameter achromatic spot centered on the fovea. Threshold recovery data were modeled, and the time constant of cone recovery (tau), initial cone thresholds, and final cone thresholds were determined. Regression analysis was used to determine the relationship between age and cone dark adaptation parameters. RESULTS: Cone tau increased by 16.4 s/decade of life, indicating a progressive slowing of dark adaptation with increasing age. This change in cone tau throughout adulthood was significant (p < 0.0005). There was no significant relationship between increasing age and initial cone threshold (p = 0.84) or final cone threshold (p = 0.82). CONCLUSIONS: Our results provide evidence for age-related slowing of cone dark adaptation after a full bleach in healthy adults, which is likely to contribute to visual difficulties when moving from bright to dim photopic light levels. We propose that the sensitivity and specificity of cone tau as a biomarker for early age-related macular disease could be improved by taking into account the significant age-related decline in this parameter. PMID- 22773177 TI - Delivery of ketotifen fumarate by commercial contact lens materials. AB - PURPOSE: To investigate the uptake and delivery of the anti-allergy drug ketotifen fumarate (KF) by commercially available contact lenses. METHODS: A total of 14 different commercially available contact lenses were investigated, including five frequent-replacement silicone hydrogels, three conventional hydrogels, and six daily disposable lenses. Lenses were soaked in a 0.025% KF loading solution for 24 h, and the concentration of KF in solution over time was determined by ultraviolet absorbance at 297 nm. After the 24-h loading period, lenses were placed in fresh vials containing borate buffered saline, and the release of drug into solution at 34 degrees C was monitored for 24 h. RESULTS: All the lenses studied demonstrated significant uptake and release of KF into the borate buffered saline (p < 0.05 compared with initial time point). Lenses with charged surfaces [balafilcon A, etafilcon A, and etafilcon A (daily disposable)] demonstrated the greatest uptake and release of KF. Etafilcon A released 284.5 +/ 29.8 MUg/lens, whereas balafilcon A released 227.6 +/- 14.7 MUg/lens, which was substantially more (p < 0.05) than the lowest releasing lenses [nelfilcon A (40.4 +/- 4.1 MUg/lens) and comfilcon A (110.4 +/- 8.9 MUg/lens)]. The majority of lenses were able to match or exceed the total amount of KF commonly administered to the eye using twice-daily dosing of commercially available (0.025%) eye drop formulations. Most of the lenses surveyed reached a plateau concentration of KF relatively quickly, and no lens was able to release KF for longer than 4 h. CONCLUSIONS: Commercially available lenses demonstrated the ability to release a clinically relevant amount of KF compared with conventional eye drops. The use of commercially available contact lenses as a KF delivery system in a daily wear scenario may be feasible. PMID- 22773178 TI - Mesopic pupil size in a refractive surgery population (13,959 eyes). AB - PURPOSE: To evaluate factors that may affect mesopic pupil size in refractive surgery candidates. METHODS: Medical records of 13,959 eyes of 13,959 refractive surgery candidates were reviewed, and one eye per subject was selected randomly for statistical analysis. Detailed ophthalmological examination data were obtained from medical records. Preoperative measurements included uncorrected distance visual acuity, corrected distance visual acuity, manifest and cycloplegic refraction, topography, slit lamp examination, and funduscopy. Mesopic pupil size measurements were performed with Colvard pupillometer. Relationship between mesopic pupil size and age, gender, refractive state, average keratometry, and pachymetry (thinnest point) were analyzed by means of ANOVA (+ANCOVA) and multivariate regression analyses. RESULTS: Overall mesopic pupil size was 6.45 +/- 0.82 mm, and mean age was 36.07 years. Mesopic pupil size was 5.96 +/- 0.8 mm in hyperopic astigmatism, 6.36 +/- 0.83 mm in high astigmatism, and 6.51 +/- 0.8 mm in myopic astigmatism. The difference in mesopic pupil size between all refractive subgroups was statistically significant (p < 0.001). Age revealed the strongest correlation (r = -0.405, p < 0.001) with mesopic pupil size. Spherical equivalent showed a moderate correlation (r = 0.136), whereas keratometry (r = -0.064) and pachymetry (r = -0.057) had a weak correlation with mesopic pupil size. No statistically significant difference in mesopic pupil size was noted regarding gender and ocular side. The sum of all analyzed factors (age, refractive state, keratometry, and pachymetry) can only predict the expected pupil size in <20% (R = 0.179, p < 0.001). CONCLUSIONS: Our analysis confirmed that age and refractive state are determinative factors on mesopic pupil size. Average keratometry and minimal pachymetry exhibited a statistically significant, but clinically insignificant, impact on mesopic pupil size. PMID- 22773179 TI - Spherical aberration from myopic excimer laser ablation for aspheric and non aspheric profiles. AB - PURPOSE: To evaluate the difference in the spherical aberration (SA) induced by an aspheric and a non-aspheric myopic ablation profile with the MEL80 excimer laser (Carl Zeiss Meditec). METHODS: This was a prospective randomized paired-eye controlled study of 15 patients (30 eyes) who underwent LASIK using the Hansatome microkeratome (160 MUm) (Bausch & Lomb) and the MEL80 using a 6 mm optical zone. For each patient, one eye was treated with an aspheric (Aberration Smart Ablation [ASA]) profile and the other eye was treated with a non-aspheric (Tissue Saving Ablation [TSA]) profile, assigned at random. Patients were measured before and 3 months after LASIK with the wavefront supported custom ablation aberrometer (Carl Zeiss Meditec), and SA was measured with an analysis zone of 3 to 7 mm in 0.5 mm intervals. The area under the curve of SA plotted against analysis zone (RAWS) was calculated. RESULTS: The mean spherical equivalent refraction was -2.43 +/- 1.53 D for the ASA group and -2.54 +/- 1.47 D for the TSA group (p = 0.87). There was a statistically significant increase in SA for an analysis zone of 6.0 to 7.0 mm for the ASA group and for an analysis zone of 4.5 to 7.0 mm for the TSA group. At the 6 mm zone, the increase in SA was 0.032 in the ASA group and 0.069 in the TSA group. The induction of SA per diopter was 0.024 MUm/D in the ASA group and 0.035 MUm/D in the TSA group. The RAWS parameter increased by 34.8% in the ASA group and 74.4% in the TSA group. CONCLUSIONS: There was less induction of SA in myopic LASIK with an aspheric ablation profile than with a non-aspheric ablation profile. PMID- 22773180 TI - Orthokeratology vs. spectacles: adverse events and discontinuations. AB - PURPOSE: To assess the relative clinical success of orthokeratology contact lenses (OK) and distance single-vision spectacles (SV) in children in terms of incidences of adverse events and discontinuations over a 2-year period. METHODS: Sixty-one subjects 6 to 12 years of age with myopia of - 0.75 to - 4.00DS and astigmatism <=1.00DC were prospectively allocated OK or SV correction. Subjects were followed at 6-month intervals and advised to report to the clinic immediately should adverse events occur. Adverse events were categorized into serious, significant, and non-significant. Discontinuation was defined as cessation of lens wear for the remainder of the study. RESULTS: Thirty-one children were corrected with OK and 30 with SV. A higher incidence of adverse events was found with OK compared with SV (p < 0.001). Nine OK subjects experienced 16 adverse events (7 significant and 9 non-significant). No adverse events were found in the SV group. Most adverse events were found between 6 and 12 months of lens wear, with 11 solely attributable to OK wear. Significantly more discontinuations were found with SV in comparison with OK (p < 0.05). CONCLUSIONS: The relatively low incidence of adverse events and discontinuations with OK is conducive for the correction of myopia in children with OK contact lenses. PMID- 22773181 TI - Combinatorial wetting in colour: an optofluidic nose. AB - We present a colourimetric litmus test for simple differentiation of organic liquids based on wetting, which achieves chemical specificity without a significant sacrifice in portability or ease-of-use. Chemical specificity is derived from the combination of colourimetric wetting patterns produced by liquids in an array of inverse opal films, each having a graded wettability, but using different surface groups to define that gradient. PMID- 22773182 TI - Spinous process plate (S-plate) fixation after posterior interbody fusion for lumbar canal stenosis due to spondylolisthesis. PMID- 22773183 TI - Endoscopic submucosal dissection -- initial experience from India: a case series of five patients. AB - Endoscopic submucosal dissection (ESD) is an established modality of treatment of mucosal and submucosal tumors (SMTs) of the gastrointestinal (GI) tract. Although the technique is established in the eastern countries, currently there are no reports of this technique from India. We present here our initial experience of 5 patients with mucosal or SMTs at various locations in the GI tract treated by ESD. The criteria for patient selection, technical challenges encountered during the procedure and future directions for ESD development in India are discussed. PMID- 22773184 TI - Cell-based microfluidic device for screening anti-proliferative activity of drugs in vascular smooth muscle cells. AB - This paper presents a microfluidic device consisting of five parallel microchambers with integrated readout-grid for the screening of anti proliferative activity of drugs in vascular smooth muscle cells (VSMC). A two level SU-8 master was fabricated and replicated with poly(dimethylsiloxane), PDMS, using standard soft-lithographic methods. The relative small height (4-10 MUm) of the integrated grid allowed the identification of single-cells or cell groups and the monitoring of their motility, morphology and size with time, without disturbing their proliferation pattern. This is of particular interest when considering VSMC which, apart of being crucial in the atherosclerotic process, do not proliferate in a single layer but in a non-homogenous hill and valley phenotype. The performance of the microfluidic device has been validated by comparison with conventional culturing methods, proving that the cell proliferation remains unaffected by the microchamber structure (with the integrated grid) and the experimental conditions. Finally, the microfluidic device was also used to evaluate the anti-proliferative activity of curcumin and colchicine in VSMC. With this cellular type, the anti-proliferative activity of curcumin (IC(50) =35 +/- 5 MUM) was found to be much lower than colchicine (IC(50) =3.2 +/- 1.2 MUM). These results demonstrate the good performance of the microfluidic device in the evaluation of the anti-proliferative activity (or cytotoxicity) of drugs. PMID- 22773185 TI - Tumour-secreted miR-9 promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway. AB - Angiogenesis plays a crucial role during tumorigenesis and much progress has been recently made in elucidating the role of VEGF and other growth factors in the regulation of angiogenesis. Recently, microRNAs (miRNAs) have been shown to modulate a variety of physiogical and pathological processes. We identified a set of differentially expressed miRNAs in microvascular endothelial cells co-cultured with tumour cells. Unexpectedly, most miRNAs were derived from tumour cells, packaged into microvesicles (MVs), and then directly delivered to endothelial cells. Among these miRNAs, we focused on miR-9 due to the strong morphological changes induced in cultured endothelial cells. We found that exogenous miR-9 effectively reduced SOCS5 levels, leading to activated JAK-STAT pathway. This signalling cascade promoted endothelial cell migration and tumour angiogenesis. Remarkably, administration of anti-miR-9 or JAK inhibitors suppressed MV-induced cell migration in vitro and decreased tumour burden in vivo. Collectively, these observations suggest that tumour-secreted miRNAs participate in intercellular communication and function as a novel pro-angiogenic mechanism. PMID- 22773186 TI - The p97/VCP ATPase is critical in muscle atrophy and the accelerated degradation of muscle proteins. AB - The p97/VCP ATPase complex facilitates the extraction and degradation of ubiquitinated proteins from larger structures. We therefore studied if p97 participates to the rapid degradation of myofibrillar proteins during muscle atrophy. Electroporation of a dominant negative p97 (DNp97), but not the WT, into mouse muscle reduced fibre atrophy caused by denervation and food deprivation. DNp97 (acting as a substrate-trap) became associated with specific myofibrillar proteins and its cofactors, Ufd1 and p47, and caused accumulation of ubiquitinated components of thin and thick filaments, which suggests a role for p97 in extracting ubiquitinated proteins from myofibrils. DNp97 expression in myotubes reduced overall proteolysis by proteasomes and lysosomes and blocked the accelerated proteolysis induced by FoxO3, which is essential for atrophy. Expression of p97, Ufd1 and p47 increases following denervation, at times when myofibrils are rapidly degraded. Surprisingly, p97 inhibition, though toxic to most cells, caused rapid growth of myotubes (without enhancing protein synthesis) and hypertrophy of adult muscles. Thus, p97 restrains post-natal muscle growth, and during atrophy, is essential for the accelerated degradation of most muscle proteins. PMID- 22773187 TI - Dual functions of DP1 promote biphasic Wnt-on and Wnt-off states during anteroposterior neural patterning. AB - DP1, a dimerization partner protein of the transcription factor E2F, is known to inhibit Wnt/beta-catenin signalling along with E2F, although the function of DP1 itself was not well characterized. Here, we present a novel dual regulatory mechanism of Wnt/beta-catenin signalling by DP1 independent from E2F. DP1 negatively regulates Wnt/beta-catenin signalling by inhibiting Dvl-Axin interaction and by enhancing poly-ubiquitination of beta-catenin. In contrast, DP1 positively modulates the signalling upon Wnt stimulation, via increasing cytosolic beta-catenin and antagonizing the kinase activity of NLK. In Xenopus embryos, DP1 exerts both positive and negative roles in Wnt/beta-catenin signalling during anteroposterior neural patterning. From subcellular localization analyses, we suggest that the dual roles of DP1 in Wnt/beta-catenin signalling are endowed by differential nucleocytoplasmic localizations. We propose that these dual functions of DP1 can promote and stabilize biphasic Wnt on and Wnt-off states in response to a gradual gradient of Wnt/beta-catenin signalling to determine differential cell fates. PMID- 22773188 TI - Muscle atrophy in aging and chronic diseases: is it sarcopenia or cachexia? AB - Cachexia and sarcopenia present several analogies in both the pathogenic mechanisms and the clinical picture. The loss of muscle mass and strength is a hallmark of these two clinical conditions. Although frequently overlapping and often indistinguishable, especially in old individuals, these two conditions should be considered distinct clinical entities. A prompt and accurate patient evaluation, guiding the physician through a proper differential diagnostic procedure and providing the best therapeutic options, is recommended. Given the several commonalities between cachexia and sarcopenia, it is likely that the therapeutic approaches may prove effective in both conditions. This review focuses on the most recent available literature and aims at providing physicians with the correct tools that are available to aid in diagnosing these two different entities that often clinically overlap. Currently available or proposed therapeutic strategies for pre-cachexia, cachexia and sarcopenia are also briefly described. PMID- 22773189 TI - Emergency management of puerperal breast abscess. PMID- 22773190 TI - Reflux and aerodigestive tract diseases. AB - Gastroesophageal reflux disease can present with a wide variety of extraesophageal symptoms. In particular, the type of disease characterized predominately by laryngopharyngeal reflux may be difficult to diagnose because of the absence of regurgitation or heartburn. The available battery of diagnostic tools is often insufficient to confirm a diagnosis of reflux, so the diagnosis is often made by elimination. In many cases, treatment with proton pump inhibitors will relieve symptoms and respiratory complications, despite the persistence of non-acidic reflux. Such treatment is often employed to "confirm" the diagnosis, as measured by patient response. Many diseases have been related to this condition in the literature. The authors review knowledge about these manifestations and their relationship with refluxed gastric content. Physiopathology, symptoms and treatment are reviewed in order to clarify our understanding of laryngopharyngeal reflux diseases and related manifestations. PMID- 22773191 TI - Post-tonsillectomy hemorrhage in children: a single surgeon's experience with coblation compared to diathermy. AB - The aim of this study was to compare coblation and diathermy techniques with respect to secondary post-tonsillectomy hemorrhage (PTH). A total of 1,397 children underwent tonsillectomies with or without adenoidectomy by a single surgeon in a single center from June 2005 through December 2011. A diathermy tonsillectomy was performed on 315 patients for the first 2 years, while a coblation tonsillectomy was performed on 1,082 for the next 5 years. All patients were followed-up within 28 days of surgery by the same surgeon. The characteristics of primary and secondary PTH were analyzed with a retrospective chart review. Primary PTH did not occur in both surgical technique groups. Secondary PTH occurred in 9 patients (2.9 %) in the diathermy group and in 30 patients (2.8 %) in the coblation group. The secondary PTH rates were 1.2, 2.5, 3.8, 3.1 and 4.5 % in the first, second, third, fourth and fifth years after employment of the coblation tonsillectomy, respectively (P = 0.243). Sex, age, tonsil size and severity of tonsillar embedding were not significant factors for PTH. The coblation technique was associated more with late secondary PTH than diathermy technique (odds ratio 9.14, P = 0.049). Analysis of the time of onset of PTH showed that secondary PTH occurred most commonly between 6 p.m. and 6 a.m. In summary, coblation technique has similar secondary PTH rate with diathermy technique although it has increased late secondary PTH rate in children. Coblation technique can be a good alternative to the diathermy technique. PMID- 22773192 TI - A matched cohort comparison of mTHPC-mediated photodynamic therapy and trans-oral surgery of early stage oral cavity squamous cell cancer. AB - Photodynamic therapy (PDT) of early stage oral cavity tumors have been thoroughly reported. However, statistical comparison of PDT to the surgical treatment is not available in published literature. We have identified and matched cohorts of patients with early stage oral cavity cancers undergoing surgery (n = 43) and PDT (n = 55) from a single institute experience. The groups are matched demographically and had the same pre-treatment screening and follow-up schedule. Both groups consisted only of tumors thinner than 5 mm to ensure comparability. The endpoints were local disease free survival, disease free survival, overall survival and response to initial treatment. Local disease free survival at 5 years were 67 and 74 % for PDT and surgery groups, respectively [univariate HR = 1.9 (p = 0.26), multivariable HR = 2.7 (p = 0.13)]. Disease free survival at 5 years are 47 and 53 % for PDT and surgery groups, respectively [univariate HR = 0.8 (p = 0.52), multivariable HR = 0.75 (p = 0.45)]. Overall survival was 83 and 75 % for PDT and surgery groups, respectively [(univariate HR = 0.5 (p = 0.19), multivariable HR = 0.5 (p = 0.17)]. In the PDT group, six patients (11 %) and in the surgery group 11 patients (26 %) had to receive additional treatments after the initial. All of the tested parameters did not have statistical significant difference. Although there is probably a selection bias due to the non-randomized design, this study shows that PDT of early stage oral cavity cancer is comparable in terms of disease control and survival to trans-oral resection and can be offered as an alternative to surgical treatment. PMID- 22773193 TI - Investigations of amino acids in the ATP binding site of 5,10 methenyltetrahydrofolate synthetase. AB - 5-Formyltetrahydrofolate is a compound that is administered as a rescue agent in methotrexate chemotherapy and in 5-fluorouracil chemotherapy for synergistic effects. It has also recently been suggested to play a role in bacterial resistance to antifolate therapy. 5,10-methenyltetrahydrofolate synthetase (MTHFS) is the only enzyme known to catalyze the conversion of this compound to 5,10-methenyltetrahydrofolate along with the hydrolysis of ATP to ADP. To better understand the roles of specific amino acids in the ATP binding pocket of this enzyme, we used site-directed mutagenesis to create 10 modified forms of the Mycoplasma pneumoniae ortholog. The Michaelis constant (K(m)) for each substrate and the turnover number (k(cat)) was determined for each mutant to help elucidate the role of individual amino acids. Data were compared to crystal structures of human and M. pneumoniae orthologs of MTHFS. Results were largely consistent with a simple coulombic and proximity model; the larger the predicted charges of an interaction and the closer those interactions were to the phosphate transferred between the substrates, the greater the reduction in ATP binding and catalytic activity of the enzyme. PMID- 22773194 TI - Preventive services in veterans in relation to disability. AB - Veterans with disabilities are at an increased risk of secondary impairments and may have difficulty accessing preventive services; accessibility may differ between Veterans who do and do not receive care at Department of Veterans Affairs (VA) facilities. We used data from the 2003 and 2004 Behavioral Risk Factor Surveillance System surveys to evaluate associations between disability and receipt of preventive services in Veterans. Veterans with a disability were more likely to have received influenza vaccinations (VA users and nonusers), pneumococcal vaccinations (VA nonusers: p < 0.001; VA users: p = 0.073), weight management counseling (VA nonusers: p < 0.001; male VA users: p < 0.001), lower gastrointestinal (GI) endoscopy (VA nonusers: 50-64 yr, p = 0.03; VA users: >=65 yr, p = 0.085), mammography (VA users: p = 0.097), and serum cholesterol screening (VA nonusers: p < 0.001). Receipt was similar by disability status for fecal occult blood test (FOBT), lower GI endoscopy (VA users: 50-64 yr), human immunodeficiency virus testing, and cervical cancer screening. For no measure was there significantly lower receipt in those with versus without a disability, although there was marginal evidence in VA nonusers for overall colorectal cancer screening (i.e., lower GI endoscopy or FOBT: p = 0.063). Among Veterans, having a disability did not appear to be a barrier to receiving appropriate preventive care. PMID- 22773195 TI - Who are the women and men in Veterans Health Administration's current spinal cord injury population? AB - Spinal cord injury (SCI) care is a high priority for the Veterans Health Administration (VHA). Aging Veterans, new cases of SCI from recent conflicts, and increasing numbers of women Veterans have likely changed the profile of the VHA SCI population. This study characterizes the current Veteran population with SCI with emphasis on healthcare utilization and women Veterans. We analyzed VHA administrative data from 2002-2003 and 2007-2008, analyzing composition, demographics, and healthcare use. The population is mostly male (>97%) and largely between 45 and 64 years old. Over 30% are over the age of 65. They are frequent users of healthcare, with an average of 21 visits per year. Women Veterans with SCI form a small but distinct subpopulation, being younger and less likely to be married and having a higher burden of disease. We must understand how the VHA population with SCI is changing to anticipate and provide the best care for these complex patients. PMID- 22773196 TI - Plasma variations of biomarkers for muscle damage in male nondisabled and spinal cord injured subjects. AB - Deep pressure ulcers represent a major problem for individuals with spinal cord injury (SCI), with the initial damage often hidden underneath intact skin. Accordingly, early detection is difficult and treatment is problematic. In the present study, circulatory levels of biomarkers for muscle damage were investigated to explore their potential in the early detection of deep pressure ulcers. Baseline concentrations of creatine kinase, myoglobin (Mb), heart-type fatty acid binding protein (H-FABP), and C-reactive protein (CRP) were measured in small groups of nondisabled (age 39-66 yr) subjects and subjects with SCI (age 40-68 yr, American Spinal Injury Association grade A-B, level of injury thoracic 11 to lumbar 3) over a period of 5 days. Each subject exhibited a unique concentration profile for all markers, although some correlations were observed; for example, Mb and H-FABP were correlated for both subject groups. No significant differences were found in marker concentrations between the two subject groups, although a trend toward higher CRP levels was observed in the SCI subjects. Furthermore, one SCI subject with a category II pressure ulcer exhibited higher H-FABP and CRP concentrations than all other subjects. Because the variations in each of the marker concentrations were smaller than the predicted increases after pressure ulcers, this combination of plasma markers may prove appropriate for the early detection of deep pressure ulcers. PMID- 22773197 TI - Insulin growth factors may explain relationship between spasticity and skeletal muscle size in men with spinal cord injury. AB - The major objectives of this cross-sectional study were to (1) measure insulin like growth factor-1 (IGF-1) in individuals with complete spinal cord injury (SCI) and spasticity and (2) determine the relationships between IGF-1 and cross sectional areas (CSAs) of thigh skeletal muscle groups. Eight individuals with motor complete SCI underwent magnetic resonance imaging to measure the CSA of the whole thigh, knee extensor, and knee flexor skeletal muscle groups and dual emission X-ray absorptiometry to measure fat-free mass. After participants fasted for 12 h, we measured their IGF-1 levels and determined spasticity using the Modified Ashworth Scale (MAS). Spearman rho correlations were used to test for the relationships among the tested variables, and independent t-tests were used to determine the difference in plasma IGF-1. Plasma IGF-1 was 44% greater in those with MAS scores of 2 or higher (p < 0.05). Plasma IGF-1 was positively related to knee extensor skeletal muscle CSA (r = 0. 83, p < 0.01). IGF-1 was strongly related to knee extensor and flexor spasticity (r = 0.88, p < 0.004). The findings suggest that IGF-1 is greater in SCI individuals with increased spasticity, and this may explain the strong positive relationships that were noted between spasticity and skeletal muscle CSA. PMID- 22773198 TI - Impact of adding artificially generated alert sound to hybrid electric vehicles on their detectability by pedestrians who are blind. AB - A repeated-measures design with block randomization was used for the study, in which 14 adults with visual impairments attempted to detect three different vehicles: a hybrid electric vehicle (HEV) with an artificially generated sound (Vehicle Sound for Pedestrians [VSP]), an HEV without the VSP, and a comparable internal combustion engine (ICE) vehicle. The VSP vehicle (mean +/- standard deviation [SD] = 38.3 +/- 14.8 m) was detected at a significantly farther distance than the HEV (mean +/- SD = 27.5 +/- 11.5 m), t = 4.823, p < 0.001, but no significant difference existed between the VSP and ICE vehicles (mean +/- SD = 34.5 +/- 14.3 m), t = 1.787, p = 0.10. Despite the overall sound level difference between the two test sites (parking lot = 48.7 dBA, roadway = 55.1 dBA), no significant difference in detection distance between the test sites was observed, F(1, 13) = 0.025, p = 0.88. No significant interaction was found between the vehicle type and test site, F(1.31, 16.98) = 0.272, p = 0.67. The findings of the study may help us understand how adding an artificially generated sound to an HEV could affect some of the orientation and mobility tasks performed by blind pedestrians. PMID- 22773199 TI - Standard task set for evaluating rehabilitation interventions for individuals with arm paralysis. AB - We have developed a set of upper-limb functional tasks to guide the design and test the performance of rehabilitation technologies that restore arm motion in people with high tetraplegia. Our goal was to develop a short set of tasks that would be representative of a much larger set of activities of daily living (ADLs), while also being feasible for a user of a unilateral, implanted functional electrical stimulation (FES) system. To compile this list of tasks, we reviewed existing clinical outcome measures related to arm and hand function and were further informed by surveys of patient desires. We ultimately selected a set of five tasks that captured the most common components of movement seen in ADLs and is therefore highly relevant for assessing FES-restored unilateral arm function in individuals with high cervical spinal cord injury. The tasks are intended to be used when setting design specifications and for evaluating and standardizing rehabilitation technologies under development. While not unique, this set of tasks will provide a common basis for comparing different interventions (e.g., FES, powered orthoses, robotic assistants) and testing different user command interfaces (e.g., sip-and-puff, head joysticks, brain computer interfaces). PMID- 22773200 TI - Strength evaluation of prosthetic check sockets, copolymer sockets, and definitive laminated sockets. AB - A prosthesis encounters loading through forces and torques exerted by the person with amputation. International Organization for Standardization (ISO) standard 10328 was designed to test most lower-limb prosthetic components. However, this standard does not include prosthetic sockets. We measured static failure loads of prosthetic sockets using a modified ISO 10328 and then compared them with the criteria set by this standard for other components. Check socket (CS) strengths were influenced by thickness, material choice, and fabrication method. Copolymer socket (CP) strengths depended on thickness and fabrication methods. A majority of the CSs and all of the CPs failed to pass the ISO 10328 ductile loading criterion. In contrast, the strengths of definitive laminated sockets (DLs) were influenced more by construction material and technique. A majority of the DLs failed to pass the ISO 10328 brittle loading criterion. Analyzing prosthetic sockets from a variety of facilities demonstrated that socket performance varies considerably between and within facilities. The results from this article provide a foundation for understanding the quality of prosthetic sockets, some insight into possible routes for improving the current care delivered to patients, and a comparative basis for future technology. PMID- 22773201 TI - Validity of method to quantify transtibial amputees' free-living prosthetic wearing times and physical activity levels when using suction suspension sockets. AB - Prostheses are prescribed to restore the mobility of people with amputated lower limbs. Monitoring the prosthesis wearing times and physical activity of prosthesis users would provide invaluable information regarding rehabilitation progress and suitability of the prosthesis. The validation of a method to determine wearing times and physical activity state, as well as strides taken, of amputees wearing suction suspension sockets is reported. Eight participants with transtibial amputation were fitted with custom-made suction sockets. Analysis algorithms were used to automatically characterize physical activity based on the pressure at the socket's relief valve. The algorithms were validated in a laboratory-based protocol that included walking, stair climbing, standing, sitting, donning, and doffing. Intraclass correlation coefficient (2,1) values of >0.98 were achieved with mean differences of - 2.0%, 0.3%, 1.3%, and 0.7% for agreement between "off," "static," and "dynamic" times and stride count, respectively, as determined by the analysis algorithms and a concurrent video analysis. This study demonstrates that an interpretation of the pressure at the pressure-relief valve of suction suspension sockets can be used to determine wearing times and activity state. PMID- 22773202 TI - Assessment of upper-body dynamic stability during walking in patients with subacute stroke. AB - The analysis of upper-body acceleration is a promising and simple technique to quantitatively assess dynamic gait stability. However, this method has rarely been used for people with stroke, probably because of some technical issues still not addressed. We evaluated the root-mean-square (RMS) and harmonic ratio of trunk accelerations for a group of 15 inpatients with subacute stroke who were able to walk (61.4 +/- 14.9 yr) and compared them with those of an age-matched group of nondisabled subjects (65.1 +/- 8.8 yr) and those of a highly functional group of young nondisabled subjects (29.0 +/- 5.0 yr). Small (<2%) but significant (p < 0.03) differences were found in RMS values obtained by applying the two most common computational approaches: (1) averaging among individual stride RMS values and (2) computing the RMS value over the entire walking trial without stride partitioning. We found that the intersubject dependency of acceleration RMS values by selected walking speed was specific for each group and for each of the three body axes. The analysis of ratios between these three accelerations provided informative outcomes correlated with clinical scores and not affected by walking speed. Our findings are an important step toward transferring accelerometry from human movement analysis laboratories to clinical settings. PMID- 22773203 TI - Single session of brief electrical stimulation immediately following crush injury enhances functional recovery of rat facial nerve. AB - Peripheral nerve injuries lead to a variety of pathological conditions, including paresis or paralysis when the injury involves motor axons. We have been studying ways to enhance the regeneration of peripheral nerves using daily electrical stimulation (ES) following a facial nerve crush injury. In our previous studies, ES was not initiated until 24 h after injury. The current experiment tested whether ES administered immediately following the crush injury would further decrease the time for complete recovery from facial paralysis. Rats received a unilateral facial nerve crush injury and an electrode was positioned on the nerve proximal to the crush site. Animals received daily 30 min sessions of ES for 1 d (day of injury only), 2 d, 4 d, 7 d, or daily until complete functional recovery. Untreated animals received no ES. Animals were observed daily for the return of facial function. Our findings demonstrated that one session of ES was as effective as daily stimulation at enhancing the recovery of most functional parameters. Therefore, the use of a single 30 min session of ES as a possible treatment strategy should be studied in human patients with paralysis as a result of acute nerve injuries. PMID- 22773204 TI - Is it important to position foot in subtalar joint neutral position during non weight-bearing molding for foot orthoses? AB - When taking molds for foot orthoses, it is accepted practice to position the subtalar joint in its neutral position. However, foot orthoses have no contact with the talus, and this leads to a hypothesis that as long as there is correction available to appropriately align the forefoot relative to the hindfoot when taking a mold, changes in subtalar joint angles do not lead to significant alterations in the plantar surface shapes of the molds taken. This study tested this presumption with 20 subjects between 22 and 46 years old. During non-weight bearing casting, the subtalar joints were aligned at positions of 4 degrees of eversion, 2 degrees of eversion, 2 degrees of inversion, and in neutral. At each orientation, forces were applied over the forefoot such that the metatarsal heads were aligned with the rearfoot. Digital scanning was used to analyze the shape of each negative mold. There were significant changes in projection volume in different subtalar joint orientations. However, the changes in arch heights, navicular height, and protrusion were insignificant and very small. It is therefore suggested that as long as the forefoot and hindfoot are appropriately aligned, variations in the orientation of the subtalar joint would be acceptable. PMID- 22773205 TI - Accelerometer output and its association with energy expenditure in persons with multiple sclerosis. AB - Limited data support the strong association between rates of accelerometer activity counts and energy expenditure during dynamic activity in persons with multiple sclerosis (MS). This study examined the association between rates of activity counts and energy expenditure during walking by using two models of accelerometers and generated cut-points representing moderate-to-vigorous physical activity (MVPA) in persons with MS. Participants were 43 persons with MS and 43 controls who undertook 5 min of seated rest and up to five 6 min periods of walking at five different speeds on a treadmill. While walking, participants wore two models of accelerometers and a mouthpiece in-line with an open-circuit spirometry system for measuring energy expenditure (rate of oxygen consumption). Strong linear associations were found between accelerometer activity counts and energy expenditure, and the magnitude did not differ between MS and controls for both accelerometer models. The mean slopes of the linear relationships were steeper in persons with MS than controls and resulted in distinct cut-points for MVPA based on accelerometer counts for persons with MS and controls. The strong linear relationship between activity counts and energy expenditure and cut-points for quantifying time spent in MVPA should allow for better understanding of physical activity and examination of its predictors and consequences when using accelerometers in MS. PMID- 22773206 TI - Community-Based Wounded Warrior Sustainability Initiative (CBWSI): an integrative medicine strategy for mitigating the effects of PTSD. PMID- 22773207 TI - Response to Barnett et al. Small N designs for rehabilitation research. J Rehabil Res Dev. 2012;49(1):175-86. PMID- 22773208 TI - [Dyspnea, fatigue and subpulmonary mass]. AB - A 52-year-old man was referred for progressive dyspnea and fatigue. The medical history was unremarkable and there were no signs of late infections or previous tumorous diseases. Physical examination revealed diminished breath sounds and a dull tone over the right lower side. Routine blood tests, arterial blood gas and body plethysmography were all within normal ranges. Chest X-ray and thorax computed tomography (CT) showed the presence of a homogeneous subpulmonary mass with a diameter of 10 cm which had a water-like density of approximately 1 Hounsfield unit (HU). The presence of an extraordinary large pericardial cyst compromising the right lower lobe and therefore causing dyspnea was confirmed by video-assisted thoracoscopic surgery (VATS). Pericardial cysts are rare congenital mediastinal masses. They are usually asymptomatic and are usually found incidentally during routine chest X-ray, CT, magnetic resonance imaging (MRI) or echocardiography. Most pericardial cysts are situated at the right cardiophrenic angle. When reaching a relevant size they can cause symptoms such as dyspnea, coughing, chest pain and fatigue. The imaging studies most useful for diagnosis are CT, MRI and echocardiography. Differential diagnoses are diaphragmatic hernia, trapped pleural effusion or other pleural or mediastinal tumors. PMID- 22773209 TI - (Bortezomib plus lenalidomide/thalidomide)- vs. (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma: a meta-analysis of randomized controlled trials. AB - The aim of the study was to perform a meta-analysis of the efficacy and safety of (bortezomib plus lenalidomide/thalidomide)- vs. (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma. We searched electronic and printed sources for relevant articles published. Inclusion criteria was as follows: randomized controlled trials (RCT) of (bortezomib plus lenalidomide/thalidomide) vs. (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma. Two reviewers independently assessed potentially eligible studies and extracted relevant data. We retrieved five RCT studies including a total of 1,200 patients. Using the random-effects model to pool the five RCT with a statistically significant heterogeneity (P = 0.03; X2 = 10.69; df = 4; I2 = 63%), the weighted risk ratios of a complete response (CR) for (bortezomib plus lenalidomide/thalidomide)-containing regimens was 1.81 (P = 0.005; 95% CI: 1.20-2.73). When we excluded the study by Cavo et al. (Lancet 376:2075-2085, 2010), the pooled risk ratio for CR was 1.59 (P < 0.0001, 95% CI: 1.29-1.96) with no statistically significant heterogeneity (P = 0.54; X2 = 2.14; df = 3; I2 = 0%) among four RCT under the fixed effects mode. The pooled odds ratio for the main grade III/IV adverse events (the peripheral neuropathy, thrombotic events, and infections) were 1.76 (P = 0.32; 95% CI: 0.58-5.31), 0.92 (P = 0.76, 95% CI: 0.52-1.61), and 1.05 (P = 0.82, 95% CI: 0.70-1.57), respectively. Our analysis showed (bortezomib plus lenalidomide/thalidomide) containing regimens as induction treatment in newly diagnosed multiple myeloma improved CR but did not increase the risk of major adverse events (the peripheral neuropathy, thrombotic events, and infections). PMID- 22773210 TI - Penile cancer in India: a clinicoepidemiological study. AB - INTRODUCTION: Penile cancer is one of the most common genitourinary cancers encountered in developing countries like India. The incidence of carcinoma of the penis varies according to circumcision practice, hygienic standard, phimosis, the number of sexual partners, HPV infection, exposure to tobacco products, and other factors. The aim of the study was to study the clinic-epidemiological profile of penile cancer. MATERIALS AND METHODS: 54 patients were enrolled and studied from May 2005 to June 2006. Clinicoepidemiologic profile and patients' characteristics were assessed in a questionnaire including demographic data, presence of risk factors like smoking, phimosis, circumcision, history of promiscuity, history of sexually transmitted disease etc., clinical features, pathological features of tumor like size, site, appearance, histological type, grade, presence of lymph nodes, treatment performed and response. 5 year survival rates were also calculated. RESULTS: Of the 54 patients, about three-fourths patients were older than 50. About one quarter patients presented with phimosis and 20% patients had undergone circumcision after attaining adulthood. 70% patients were found to be smokers. Most patients presented with T2 disease whereas lymphadenopathy, both benign and malignant, was present in 55.5% and 76% patients in T1 and T2 patients respectively. 5 year survival rates were found to be 87% and 60% respectively in stage I and II respectively. CONCLUSION: penile cancer is one of the most common genitourinary cancer affecting mostly aged, uncircumcised males with history of smoking.Most patients present at advanced age and hence a national awareness campaign against this disease should be promoted. PMID- 22773211 TI - Gastric Cancer: a retrospective analysis from AIIMS, New Delhi. AB - Carcinoma of stomach is the leading cause of cancer related death in the last century worldwide. However in many parts of the world, the incidence has gradually decreased due to changes in food habit and the environment. The proximal gastric and gastro-esophageal junction (GE junction) cancer has markedly increased in the last three decades. The only proven curative treatment is surgery, but due to high recurrence rate, efforts are still going on regarding better systemic and regional adjuvant therapies. The present study is a retrospective analysis of all the post-operative (post-op) cases of carcinoma stomach and the GE junction being registered and treated in our department from June 1995 to February 2008. The total number (no.) of patients (pts) were 69 (54 stomach, 15 GE junction), males 49, females 20, KPS 50-90 (median 80), length of the lesion was <5cm in 28 pts, transmural infiltration along with serosa involvement was found in 40 pts. Histologically, adenocarcinoma was detected in 61 pts and metastatic spread in 50 pts. Thirty-six pts had surgery in another center prior to registration. Forty-nine pts had subtotal gastrectomy, while lymph nodes dissection was done in 64 pts. Chemo-radiotherapy (CRT) was given in 49 pts, and 54 pts received >30 Gy dose of radiation. Macdonald's regimen was used in 49 pts. Treatment compliance was found in 53 pts, but only 05 pts were hospitalized for supportive management. Pts were followed up from 01-69 months (median 12 months) and the recurrence was found in 13 pts (median 14 months). The multimodality intervention is better treatment option in the management of carcinoma of stomach. PMID- 22773212 TI - Intensity Modulated Radiotherapy (IMRT) in head and neck cancers - an overview. AB - Radiotherapy (RT) is effective in head and neck cancers. Following RT, dryness and dysphagia are the 2 major sequelae which alter the quality of life (QOL) significantly in these patients. There is randomized evidence that Intensity Modulated Radiotherapy (IMRT) effectively spares the parotid glands. IMRT has been attempted in all head and neck subsites with encouraging results (discussed below). Role of IMRT in swallowing structure (constrictor muscles) sparing is less clear.Further improvement in results may be possible by using functional imaging at the time of RT planning and by image guidance/verification at the time of treatment delivery. The following text discusses these issues in detail. KEYWORDS: Head and neck cancer, IMRT. PMID- 22773213 TI - Adult T-cell leukemia/lymphoma. AB - The adult T-cell leukemia/lymphoma (ATLL) syndromes comprise neoplasms that arise in peripheral lymphoid tissues but a high frequency present with blood involvement mimicking T-cell leukemia. Clinically ATLL is sub-classified into four groups: acute, lymphomatous, chronic and smoldering. ATLL is etiologically linked to the human T-cell lymphotropic virus type I (HTLV-I). The diagnosis of ATLL is based upon a combination of characteristic clinical manifestations, morphological and immunophenotypic changes of the malignant cells, in addition to the confirmation of HTLV-I infection. ATLL is an aggressive malignancy with a median survival of less than 12 months and no successful treatment yet available. Patients are either refractory or only transiently respond to chemotherapy or purine analogues. Smoldering and chronic ATLL pursue an indolent course and survival for years until the disease progresses and becomes refractory to therapy. The major causes of death in ATLL are opportunistic pulmonary infections and progressive disease, often in association with hypercalcemia. PMID- 22773214 TI - Adrenocortical tumors in children: a Kuwait experience. AB - INTRODUCTION: Adrenocortical tumors (ACT) are rare tumors of childhood. The majority of these tumors is hormone-producing and cause virilization and Cushing syndrome or feminization. METHODOLOGY: The authors describe 6 cases of adrenal cortical tumors treated at the Kuwait Cancer Center which were presented over a period of 20 years (1989-2009). RESULTS: The mean age was 5.5 years (range 15 months - 12 years). All had signs of virilization. One child had hypertension, while 2 had a metastatic disease at presentation. The diagnosis was made by clinical signs and symptoms, high levels of relevant adrenal hormones and imaging. Two children were not fit for surgery; one was too sick for any treatment and died shortly after diagnosis, while the other died after receiving one cycle of palliative chemotherapy. Four patients underwent complete surgical resection and achieved complete remission, three of whom later had recurrence (distant in one and local in two patients) and succumbed due to progressive disease. Mitotane was used in two children. Only one patient is currently surviving and well nearly 13 years after her surgery. In our series, the long term outcome of children with adrenocortical tumors was very poor. CONCLUSIONS: Virilization is an important clue to the diagnosis of ACT. Early diagnosis and complete surgical resection are important for survival. Metastasis at presentation or as recurrence carries very dismal prognosis. PMID- 22773215 TI - Limb sparing surgery in soft tissue sarcoma of extremities: an Indian perspective. AB - This is a retrospective study of 57 patients with extremity soft tissue sarcomas treated at Gujarat Cancer Research Institute, Gujarat, India from January 2005 to December 2007. It aims to review the feasibility of limb sparing surgery for extremity soft tissue sarcoma in Indian population. Twenty-eight percent (28%) of tumors were located in the upper limbs and 72% in the lower extremities. The goal of treatment was limb salvage if feasible. The treatment consisted of amputation in 17 (30%) and local wide excision i.e. limb salvage surgery (LSS) in 40 (70%) patients. The most common histology was pleomorphic sarcoma (21%). Sixty-four percent (64%) of the patients were treated with surgery alone, 32% with surgery plus radiation and 4% with surgery plus systemic chemotherapy. Inadequate margins were present in 12% of the patients. All the patients were followed up for at least 2 years. Recurrence in the form of local and distant occurred in 39% of the patients. Local recurrence occurred in 18% of the patients who underwent LSS and in 35% of those who underwent amputation. Pulmonary metastasis was detected in 16% of patients. The 2 year mortality was 10.5% with the most common etiology being lung metastasis and the most common histology being leiomyosarcoma. We concluded that limb salvage surgery for soft tissue sarcoma is feasible in the Indian population (70%) although the rate is lower than that of world literature at 90%. PMID- 22773216 TI - Mixed germ cell tumor of ovary and clitoromegaly in Swyer's syndrome: a case report. AB - Swyer syndrome is a type of pure gonadal dysgenesis correlating with 46 XY karyotype, primary amenorrhea, and female internal and external genitalia. It reveals a testicular differentiation abnormality.A 16-year old girl admitted to our center with primary amenorrhea and abdominal mass. In spite of the absence of normal testis, clitoromegaly was noticed. Peripheral blood karyotype analysis showed 46 XY. Histopathology of the excised gonads determined mixed germ cell tumor in right ovary and streak left gonad without gonadoblastoma in left side. In patients suffering from Swyer syndrome, high risk of gonadal neoplasia dictates early prophylactic gonadal excision to lengthen survival. PMID- 22773217 TI - Palmar fasciitis and arthritis syndrome associated with metastatic ovarian cancer: a paraneoplastic syndrome. AB - Palmar fasciitis and polyarthritis syndrome (PFPA) is an uncommon syndrome that affects predominantly elderly women and characterized by symmetrical polyarthritis followed by flexioncontracture of the hands. It is usually associated with a metastatic malignant neoplasm, and therefore implies a poor prognosis. We report a case of a 54-year old woman presented with palmar fasciitis and polyarthritis six months before the diagnosis of a metastatic adenocarcinoma of the ovary. Surgical excision of the tumor and adjuvant chemotherapy caused remission of the polyarthritis. PMID- 22773218 TI - Trichilemmal pilar tumor of the scalp: a case report. AB - Proliferating trichilemmal tumors (PTTs) are uncommon exuberant growths of cells derived from the external root sheath. They tend to occur in older women, with a predilection for the scalp. Wide local excision has been the standard treatment. Recent reports have described a rare malignant variant with an aggressive clinical course and a propensity for nodal and distant metastases which, therefore, merits aggressive treatment. PMID- 22773219 TI - Carcinosarcoma of renal pelvis with immunohistochemical correlation. AB - Carcinosarcoma, a malignant tumor with biphasic morphology is uncommon in the renal pelvis. Immunohistochemistry (IHC) plays an important role in establishing the diagnosis and differentiating it from other biphasic malignant tumors. We present a rare case of immunohistologically confirmed carcinosarcoma of renal pelvis in a 42-year old female, which possibly developed on a background of multicentric squamous cell carcinoma arising as a consequence of chronic irritation caused by calculi. PMID- 22773220 TI - 5-Flourouracil cardiotoxicity - an elusive cardiopathy: case report. AB - 5-Flourouracil (5-FU) is an S-phase specific, synthetic pyrimidine antimetabolite. It is a frequently administered chemotherapeutic agent for a variety of malignant lesions, either singly or in multidrug regimens. Its adverse side effects involving bone marrow, skin, mucous membranes, GIT and CNS are well known, whereas its cardiotoxicity is relatively uncommon and occurs in 1.2-18%. PMID- 22773221 TI - An unusual variant of prostatic adenocarcinoma with metastasis to testis. A case report. AB - Ductal adenocarcinoma of the prostate is considered to be a rare variant of prostatic adenocarcinoma when compared to the more common acinar adenocarcinoma. We report here a case of ductal adenocarcinoma of the prostate in a 68-year old man who presented with complaints of abdominal pain, retention of urine and hematuria of one month duration. Clinical examination showed prostatomegaly. The serum Prostate Specific Antigen (PSA) value was raised to 79ng/mL. Histopathological and immunohistochemical evaluation of resected specimen of prostate revealed ductal adenocarcinoma of the prostate. The patient was lost to follow up and presented four years after the initial diagnosis with metastasis to the bone and testis. Though prostatic cancers have the ability for wide spread dissemination, metastasis to testis is rare. Immunohistochemical staining with PSA and Prostatic Acid Phosphatase (PAP) can help in establishing prostatic nature of the neoplasm. We are reporting this case because of the rarity of metastasis of prostatic carcinoma to testis and for stressing the need for keeping in mind the possibility of metastatic carcinoma also while dealing with testicular tumors. PMID- 22773222 TI - Mammary fibromatosis in a male breast. AB - Fibromatosis of the breast is a relatively benign, though locally invasive neoplasm. It is rare and difficult to diagnose. Risk of recurrence is there if it was inadequately excised. The best treatment is local wide excision with negative margins. We report a 46-year old gentleman with mammary fibromatosis. To the best of our knowledge, there are only few cases reported on male breast fibromatosis. The optimal management of it is unknown because of the rarity of the disease. PMID- 22773223 TI - Primary isolated extramedullary plasmacytoma of mesentry: a rare case report. AB - Extramedullary plasmacytoma (EMP) is an uncommon entity that most commonly involves nasopharynx and upper repository tract. Involvement of GIT occurs in approximate 10% of cases. According to WHO plasma cell tumors have been classified into two main groups: Multiple myeloma and plasmacytoma. Plasmacytoma includes solitary plasmacytoma of bone and solitary extramedullary plasmacytoma. EMP can be either primary without evidence of bone marrow involvement or may occur simultaneously with multiple myeloma representing extramedullary spread of the disease. It may occur in association with multiple myeloma and it may precede, accompany or follow the onset of multiple myeloma. Diagnosis of primary EMP requires the exclusion of associated multiple myeloma as shown by negative Bence Jones Proteins in urine, normal serum electrophoresis, normal bone marrow biopsy, normal skeletal survey and normal calcium levels. Here we present a case of 55-year male who came to Nephrology Department for urinary tract infection and pain abdomen. Patient was referred to Radiology for ultrasonography which revealed bilateral renal parenchymal disease with a well-defined mass in the mesentry which was further confirmed on computed tomography. Patient was surgically operated and diagnosis of primary EMP of mesentry was made on histopathological examination. Only three cases have been reported so far in the literature. PMID- 22773224 TI - Diagnosis of subacute ruminal acidosis (SARA) by continuous reticular pH measurements in cows. AB - The objective of this study was to determine whether subacute ruminal acidosis (SARA) could be diagnosed by continuous measurements of the reticular pH, as compared with the ruminal pH, using healthy cows fed a control diet and SARA cows fed a rumen acidosis-inducing diet. The reticular and ruminal pH were measured simultaneously by a radio transmission pH measurement system. The mean reticular pH at 1-h intervals decreased gradually from the morning feeding to the next feeding time in both healthy and SARA cows, though the decrease in the ruminal pH was observed to be more drastic as compared with that observed in the reticular pH. The threshold of the 1-h mean pH in the reticulum for a diagnosis of SARA was considered to be 6.3, and a significant positive correlation was observed between the reticular and ruminal pH. No differences in the concentrations of lactic acid, ammonia nitrogen, and volatile fatty acids were noted between the reticular and ruminal fluids in SARA cows. These results demonstrate that the reticular pH can be used to detect SARA in cows, as opposed to using the ruminal pH. PMID- 22773225 TI - Social cognitive changes following weight loss and physical activity interventions in obese, older adults in poor cardiovascular health. AB - BACKGROUND: The study objectives were to determine (a) the effects of group mediated cognitive-behavioral interventions on change in performance self efficacy, satisfaction with function, and with appearance among older, overweight/obese adults in poor cardiovascular health and (b) whether self efficacy mediated change in 400-m walk time. METHODS: This translational, randomized controlled trial of physical activity and weight loss was conducted within community Cooperative Extension Centers. Participants were randomized to three intervention arms: Physical Activity, Weight Loss + Physical Activity, or a Successful Aging education control. RESULTS: Across 18 months, the Weight Loss + Physical Activity intervention demonstrated greater improvements in self efficacy, satisfaction with function, and appearance versus other trial arms. Physical Activity intervention participants also experienced significant improvements in self-efficacy and satisfaction with function versus those in Successful Aging. Self-efficacy mediated 400-m walk time at 18 months. CONCLUSIONS: Both group-mediated cognitive-behavioral interventions yielded desirable improvements in social cognitions and preserved mobility improvements post-intervention. PMID- 22773226 TI - The effect of ploidy and temporal changes in the biochemical profile of gibel carp (Carassius gibelio): a cyprinid fish species with dual reproductive strategies. AB - The basic biochemical profile of gibel carp (Carassius gibelio), diploid-triploid cyprinid species complex with dual reproduction modes, was investigated. The aim of the study was to test for the effect of fish group (which combines the effects of ploidy and sex) and temporal changes on indicators of the biochemical profile of blood in gibel carp. We showed that the basic biochemical profile of blood is significantly influenced by season and fish group. Triploid gynogenetic females had a better condition measured by total protein concentration than sexual diploids. The higher concentrations of triacylglycerols and cholesterol in triploid females when compared to diploids indicate a higher metabolic rate and higher energy intake during the whole year, which may represent a disadvantage for triploids. Differences in the concentrations of blood biochemical analytes between triploid females and diploids suggest a potential difference in the regulation of a wide range of physiological and biochemical processes in which these analytes participate. The biochemical profiles of two forms of C. gibelio could at least partially explain the changes of character of its naturally occurring populations. PMID- 22773227 TI - Strongly correlated electron systems. PMID- 22773228 TI - Determination of nitrotyrosine in Arabidopsis thaliana cell cultures with a mixed mode solid-phase extraction cleanup followed by liquid chromatography time-of flight mass spectrometry. AB - In this work, a method for the determination of trace nitrotyrosine (NO(2)Tyr) and tyrosine (Tyr) in Arabidopsis thaliana cell cultures is proposed. Due to the complexity of the resulting extracts after protein precipitation and enzymatic digestion and the strong electrospray signal suppression displayed in the detection of both Tyr and NO(2)Tyr from raw A. thaliana cell culture extracts, a straightforward sample cleanup step was proposed. It was based on the use of mixed-mode solid-phase extraction (SPE) using MCX-type cartridges (StrataTM-X-C), prior to identification and quantitation using fast liquid chromatography electrospray time-of-flight mass spectrometry. Unambiguous confirmation of both amino acids was accomplished with accurate mass measurements (with errors lower than 2 ppm) of each protonated molecule along with a characteristic fragment ion for each species. Recovery studies were accomplished to evaluate the performance of the SPE sample preparation step obtaining average recoveries in the range 92 101%. Limit of quantitation obtained for NO(2)Tyr in A. thaliana extracts was 3 nmol L(-1). Finally, the proposed method was applied to evaluate stress conditions of the plant upon different concentrations of peroxynitrite, a protein nitrating compound, which induces the nitration of Tyr at the nanomolar range. Detection and confirmation of the compounds demonstrated the usefulness of the proposed approach. PMID- 22773229 TI - Thermal fusion: effects and interactions of temperature, compression, and duration variables. AB - BACKGROUND: The constraints imposed by minimal access surgery have driven the need for enabling technologies for thermal vessel occlusion or "tissue welding." The objective of this study was to determine the values of, and interaction between, tissue temperature, apposition force, and clamp time for optimum tissue welding. METHODS: A dedicated experimental device with heated occluding jaws was used for ex vivo experiments on harvested sheep carotid vessels. The device allowed individual variation of temperature (60, 70, 80, and 90 degrees C), compression force (20, 40, 60, and 80 N) and clamp time (5, 10, 15 s). Weld strength was measured by burst pressure. RESULTS: The best seal quality was obtained at a temperature of 90 degrees C (p = 0.03), a compression force between 60 and 80 N (p = 0.03), and clamp time of 10 s (p = 0.058). The individual effects of temperature, compression force, and clamp time were all significant at p < 0.001. Although all three were considered to have large effects, clamp time had a reduced effect, relative to temperature and compression force. CONCLUSIONS: Temperature, compression force, and clamp time influence the quality of thermal welding, but the interaction between temperature and apposition force appears to be more dominant. PMID- 22773230 TI - Modified single-port laparoscopic herniorrhaphy for pediatric inguinal hernias: based on 1,107 cases in China. AB - BACKGROUND: Laparoscopic surgery is an alternative procedure for pediatric inguinal hernia (PIH), with a major trend toward increasing use of extracorporeal knotting and decreasing use of working ports. We report our experience with the modified single-port laparoscopic herniorrhaphy for repair of PIH and retrospectively evaluate a consecutive series of 1,107 cases in our institution. METHODS: Between February 2006 and July 2011, 1,107 children with indirect inguinal hernia were treated by laparoscopic surgery. All patients underwent high ligation surgery with a modified single-port laparoscopic technique, mainly performed by extracorporeal suturing with an ordinary taper needle (1/2 Arc 11 * 34). The clinical data were retrospectively analyzed. RESULTS: All surgery was successful without any serious complications. During the operations, contralateral patent processus vaginalis was found and subsequently repaired in 221 cases (20.0%). The mean operative time was 11 (range 5-14) min in 815 cases of unilateral repair and 20 (range 14-27) min in 292 cases of bilateral repair. The mean of postoperative hospital stay was 48 (range 26-52) h. Complications occurred in seven cases (0.63%) and were properly managed, with no major impact on outcome of the operations. There were six recurrent cases (0.54%) in the patients who had been followed-up for 9-74 months. There was no obvious scaring visible in any patients after treatment. CONCLUSIONS: The modified single-port laparoscopic technique for the repair of PIH is a safe and reliable procedure with minimal invasion and satisfactory outcome. It is easy to perfect and to perform and therefore is a worthy choice for PIH. PMID- 22773231 TI - Factors affecting the treatment of multiple colorectal adenomas. AB - BACKGROUND: Currently, no guidelines exist for the treatment of patients with multiple colorectal adenomas (MCRAs) (>10 but <100 synchronous nondiminutive polyps of the large bowel). This retrospective study aimed to investigate the clinical and molecular factors related to different treatments for MCRAs. METHODS: Patients with MCRAs were consecutively enrolled from January 2003 to June 2011. Sequencing of their APC and MutYH genes was performed. The clinical, molecular, and family histories of the patients were collected using the Progeny database. The patient treatments were divided into three groups of increasing clinical weight: endoscopic polypectomy, segmental resection, and total colectomy. A logistic regression analysis of clinicomolecular factors related to different treatment options was performed. RESULTS: The study comprised 80 patients (32 women, 40%) with a median age of 53 years (range 13-74 years). The median number of polyps was 33 (range 10-90).The cases included 62 diffuse polyposis, 18 segmental polyposis coli and synchronous colorectal carcinomas (CRC; 34 cases, 43%). The pathogenetic mutations were biallelic MutYH (n = 19, 24%) and APC (n = 4, 5%). The mean follow-up period was 74 months (median 43 months, range 1-468 months). Endoscopic polypectomy was performed in 25 cases (31%), segmental resection in 16 cases (20%), and total colectomy in 39 cases (49%). The logistics regression analysis, considering all the patients, showed that the number of polyps, the presence of CRC, and mutation were correlated with more intensive treatment. For the patients without CRC, only the number of polyps was correlated with the severity of the treatment (p > 0.0166). "On the ROC (receiver operating characteristic) curve, 25 was the number of polyps that best discriminated between surgical and endoscopic therapy. CONCLUSIONS: The majority of patients with MCRAs undergo surgery. For patients without CRC, only the number of polyps, and not the presence of a disease-causing mutation, is correlated with increased heaviness of treatment. Patients with more than 25 polyps are more likely to undergo a surgical resection. PMID- 22773232 TI - Development and evaluation of a simulator-based laparoscopic training program for surgical novices. AB - BACKGROUND: The use of simulation to train novice surgeons in laparoscopic skills is becoming increasingly popular. To maximize benefit from simulation, training needs to be delivered and assessed in a structured manner. This study aimed to define performance goals, demonstrate construct validity of the training program, and evaluate whether novice surgeons could reach the preset performance goals. METHODS: Nine expert laparoscopic surgeons established performance goals for three basic modules of an augmented-reality laparoscopic simulator. The three laparoscopic modules were used by 40 novice surgeons and 40 surgical trainees (postgraduate years [PGYs] 1-4). The performance outcomes were analyzed across the different groups (novice, PGYs 1 and 2, PGYs 3 and 4, expert) to determine construct validity. Then 26 recruited novices trained on the three modules with the aim of reaching the performance goals. RESULTS: The results demonstrated a significant difference in performance between all levels of experience for time (p < 0.001), motion analysis (p < 0.001), and error score (p < 0.001), thus demonstrating construct validity. All 26 novice surgeons significantly improved in performance with repetition for the metrics of time (p < 0.001) and motion analysis (p < 0.001). For two of the modules, the proficiency goals were reached in fewer than 10 trials by 80% of the study participants. CONCLUSION: Basic skills in laparoscopic surgery can be learned and improved using proficiency based simulation training. It is possible for novice surgeons to achieve predefined performance goals in a reasonable time frame. PMID- 22773233 TI - Randomized clinical trial of laparoscopic hernia repair comparing titanium-coated lightweight mesh and medium-weight composite mesh. AB - BACKGROUND: The use of lightweight meshes in incisional hernia repair could have beneficial effects on quality of life. This study aimed to compare a new titanium coated lightweight mesh with a standard composite mesh after laparoscopic incisional hernia repair. METHODS: A randomized controlled single-center clinical trial was designed using the basic principle of one unit, one surgeon, one technique (midline incisional hernia with a laparoscopic approach), and two meshes: a lightweight titanium-coated mesh (group 1) and a medium-weight collagen polyester composite mesh (group 2) used in 102 patients. The primary end points were pain and recurrence. The secondary end points were morbidity and patient outcomes (analgesic consumption, return to everyday activities). RESULTS: The postoperative complication rates were similar for the two meshes. Pain was significantly less common in group 1 than in group 2 at 1 month (P = 0.029) but was similar for the two groups at 6 months and 1 year. There was a significant difference between the two groups in the average use of analgesics: 6.1 days in group 1 versus 1.6 days in group 2 (P < 0.001). The lightweight group returned to everyday activities after 6.9 days versus 9.7 days for the composite group (P < 0.001). The rate of recurrence did not differ between the two groups at the 2 year follow-up evaluation. CONCLUSIONS: The light titanium-covered polypropylene mesh was associated with less postoperative pain in the short term, lower analgesic consumption, and a quicker return to everyday activities than the Parietex composite medium-weight mesh. The recurrence rates at 2 years showed no difference between the two groups. PMID- 22773234 TI - Cost utility of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. AB - BACKGROUND: Early laparoscopic cholecystectomy for acute cholecystitis is safe and effective. However, the potential cost savings of this management strategy have not been well studied in a North American context. This study aimed to estimate the cost effectiveness of early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy in Canada. METHODS: A decision analytic model estimating and comparing costs from a Canadian providing institution after either early or delayed laparoscopic cholecystectomy was used. The health care resources consumed were calculated using local hospital data, and outcomes were measured in quality-adjusted life years (QALYs) gained during 1 year. Uncertainty was investigated with one-way sensitivity analyses, varying the probabilities of the events and utilities. RESULTS: Early laparoscopic cholecystectomy was estimated to cost approximately $2,000 (Canadian dollars) less than delayed laparoscopic cholecystectomy per patient, with an incremental gain of approximately 0.03 QALYs. Sensitivity analysis showed that only extreme values of bile duct injury or bile leak altered the direction of incremental gain. CONCLUSIONS: Adoption of a policy in favor of early laparoscopic cholecystectomy will result in better patient quality of life and substantial savings to the Canadian health care system. PMID- 22773235 TI - Robot-assisted common bile duct exploration as an option for complex choledocholithiasis. AB - BACKGROUND: This study aimed to describe the authors' early experience with robot assisted common bile duct exploration (CBDE) for choledocholithiasis refractory to endoscopic therapy and to compare the outcomes with those of equivalent patients undergoing an open technique. METHODS: At our institution, 55 CBDEs were performed between 2005 and 2010. All 19 robot-assisted cases were unselected elective referrals for stone disease. Of 36 open procedures, emergency cases and exploration not for stone disease were excluded, leaving 18 cases for analysis. Cases were analyzed on an intent-to-treat basis. A P value of 0.05 denoted statistical significance. RESULTS: The patients did not differ in terms of demography, comorbidity, or presenting symptoms. The reasons for endoscopic failure in both groups were similar. The mean operating time was longer for robot assisted surgery (220 +/- 41.26 min) than for open surgery (169 +/- 65.81 min) (P = 0.01), but the median hospital stay was shorter (4 vs 11 days; P = 0.02). Four conversions to open surgery (21%) were performed due to severe adhesions. The two groups did not differ statistically in terms of T-tube usage (74 vs 61%; P = 0.414). One death occurred in the robotic group and two in the open cohort. Postoperative complications occurred in seven robotic and ten open cases (P = 0.402). They were mainly respiratory complications in the robot-assisted group, whereas they were cardiac and wound-related complications in the open group. Two of the converted cases had complications similar to those of the open group. Postoperative endoscopic retrograde cholangiopancreatography (ERCP) for retained stones was performed in one open case and three robotic cases. CONCLUSION: Robot assisted CBDE offers some benefit when ERCP fails. Ideal case selection may enhance success. PMID- 22773236 TI - Ensuring competency: are fundamentals of laparoscopic surgery training and certification necessary for practicing surgeons and operating room personnel? AB - BACKGROUND: Certification in fundamentals of laparoscopic surgery (FLS) is required by the American board of surgery for graduating residents. This study aimed to evaluate the feasibility and need for certifying practicing surgeons and to assess proficiency of operating room (OR) personnel. METHODS: Through a patient safety and health care delivery effectiveness grant, investigators at four state medical schools received funding for FLS certification of all attending surgeons and OR personnel credentialed in laparoscopy. Data were voluntarily collected under an institutional review board-approved protocol. Surgeons performed a single repetition of the FLS tasks oriented to the FLS proficiency-based curriculum and online cognitive materials and were encouraged to self-practice. The FLS certification examination was administered 2 months later under standard conditions. Operating room nurses and scrub technicians were enrolled in a curriculum with cognitive materials and a multistation skills practicum. Baseline and completion questionnaires were administered. Performance was assessed using signed-rank and chi(2) analysis. RESULTS: The study aimed to enroll 99 surgeons. Subsequently, 87 surgeons completed at least one portion of the curriculum, 72 completed the entire curriculum (73% compliance), 83 completed the baseline skills assessment, and 27 (33%) failed. The self-reported practice time was 3.7 +/- 2.5 h. At certification (n = 76), skills performance had improved from 317 +/- 102.9 to 402 +/- 54.2 (p < 0.0001). One surgeon (1.3%) failed the skills certification, and nine (11.8%) failed the cognitive exam. Remediation was completed by six surgeons. Of the 64 enrolled OR personnel, 22 completed the curriculum (34% compliance). All achieved proficiency at skills, and 60% passed the cognitive exam. CONCLUSIONS: This study demonstrated that FLS certification for practicing surgeons and proficiency verification for OR personnel are feasible. A baseline skills failure rate of 33% and a certification failure rate of 13% suggest that FLS certification may be necessary to ensure surgeon competency. Fortunately, with only moderate practice, significant improvement can be achieved. PMID- 22773237 TI - Randomized controlled trial comparing three methods of liver retraction in laparoscopic Roux-en-Y gastric bypass. AB - BACKGROUND: This study aimed to evaluate differences between three methods of liver retraction during laparoscopic Roux-en-Y Gastric bypass (LRYGB) and to compare novel liver retraction techniques with the traditional mechanical liver retractor in a randomized controlled trial. METHODS: In this study, 60 obese patients (26 males and 34 females) who underwent LRYGB between January and July 2010 were randomized to one of three groups (20 in each): group 1 (Nathanson liver retractor), group 2 (liver suspension tape), and group 3 (V-shaped liver suspension technique [V-LIST]). Data regarding demographics (age, sex, body mass index); liver function test (LFT) just before surgery; postoperative results immediately, then 18 h, 1 week, and 1 month after surgery; operative data, and visual analog scale (VAS) for pain on postoperative days (PODs) 1 and 2 were calculated and analyzed. RESULTS: The groups did not differ significantly in terms of preoperative LFT or operative data except that group 3 took significantly longer time for liver suspension than group 1 (p = 0.01) or group 2 (p = 0.03). The VAS score in group 2 was significantly lower on POD 1 than in group 1 (p = 0.04). Group 1 showed a significant rise in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at 18 h compared with group 2 (p < 0.01 and p = 0.02, respectively) and group 3 (p < 0.01 and p = 0.01), at 1 week compared with group 2 (p = 0.04 and 0.04), and in AST levels alone during the immediate postoperative compared with group 3 (p = 0.04). CONCLUSION: The Nathanson liver retractor causes more liver dysfunction than V LIST or the liver suspension technique and causes more postoperative pain than the liver suspension technique. Both V-LIST and liver suspension tape have a short learning curve and implications for single-port surgery. PMID- 22773238 TI - Comparison of treatment outcomes of endoscopic stenting for colonic and extracolonic malignant obstruction. AB - BACKGROUND: Self-expandable metal stents (SEMS) have been used as a bridging or palliative treatment for malignant colorectal obstruction. Colonic obstruction also may arise from advanced extracolonic malignancy, but the clinical outcomes of stent placement for extracolonic malignancy are unclear. This study compared the clinical outcomes of SEMS between patients with colorectal cancer and those with extracolonic malignancy. METHODS: Patients who underwent endoscopic SEMS placement for a malignant colorectal obstruction were enrolled at Seoul National University Hospital from April 2005 and August 2011. Their medical records were retrospectively reviewed in terms of success rate, complications, and duration of stent patency. RESULTS: Endoscopic SEMS placements were performed for colorectal cancer in 149 patients and for extracolonic malignancy in 60 patients. The causes of obstruction in extracolonic malignancy were advanced gastric cancer in 39 patients (65%), pancreatic cancer in nine patients (15%), ovarian cancer in three patients (5%) and other causes in nine patients (15%). The clinical success rates were similar between the two groups (92.6 vs 86.7%; p = 0.688), and multivariate analysis showed no significant risk factor for unsuccessful endoscopic SEMS placement. Reobstruction in palliative endoscopic SEMS placement occurred for 16 patients with colorectal cancer (21.9%) and 18 patients with extracolonic malignancy (30%) during a median follow-up period of 90 days (p = 0.288). The rates did not differ significantly between the two groups (4.1 vs 8.3%; p = 0.467). The median duration of stent patency was 193 +/- 42 days for the patients with colorectal cancer and 186 +/- 31 days for the patients with extracolonic malignancy (p = 0.253). The duration of stent patency was not affected by underlying malignancy, previous surgery, or palliative chemotherapy. CONCLUSIONS: Endoscopic SEMS placement is highly effective and comparable for palliation of obstruction in extracolonic malignancy and colorectal cancer in terms of clinical success, complications, and duration of patency. PMID- 22773239 TI - Endoscopic clip closure versus surgery for the treatment of iatrogenic colon perforations developed during diagnostic colonoscopy: a review of 115,285 patients. AB - BACKGROUND: Although the incidence of perforation after endoscopic procedures of the colon is low, the rising number of diagnostic colonoscopies could pose relevant health problems. Optimizing treatment may reduce the probability of severe complications. This study aimed to determine perforation frequency and the management of perforations that occurred during diagnostic colonoscopy. METHODS: A retrospective review of patient records was performed for all patients with iatrogenic colonic perforations after sigmoidoscopy/colonoscopy from 2000 to 2011 in three institutions of The Catholic University of Korea. The patients' demographic data, endoscopic procedure information, perforation location, therapy, and outcomes along with different therapeutic strategies were recorded. RESULTS: In the 12-year period, a total of 115,285 diagnostic sigmoidoscopic/colonoscopic procedures were performed. A total of 27 perforations occurred. Sixteen patients underwent endoscopic clipping, of which three patients failed and were referred for surgery. Fourteen patients in total underwent surgery for perforation. Endoscopic clip closure was successful in 81 % of the patients. No perforation-related major morbidity or mortality occurred. CONCLUSION: Endoscopic repair using clips can be effective for the treatment of colon perforations that occur during diagnostic colonoscopy. PMID- 22773240 TI - Somatostatin analog therapy for severe polycystic liver disease: results after 2 years. AB - BACKGROUND: We showed in a randomized double-blinded placebo-controlled clinical trial that octreotide long-acting repeatable depot.(r) (OctLAR((r))) for 12 months reduces kidney and liver growth in autosomal dominant polycystic kidney patients with severe polycystic liver disease (PLD) and liver growth in patients with severe isolated PLD. We have now completed an open-label extension for one additional year to assess safety and clinical benefits of continued use of OctLAR for 2 years (O -> O) and examined drug effect in the placebo group who crossed over to OctLAR in Year 2 (P -> O). METHODS: The primary end point was change in total liver volume (TLV) measured by magnetic resonance imaging (MRI); secondary end points were changes in total kidney volume (TKV) measured by MRI, glomerular filtration rate (GFR), quality of life (QOL), safety, vital signs and laboratory parameters. RESULTS: Forty-one of 42 patients received OctLAR (n = 28) or placebo (n = 14) in Year 1 and received OctLAR in Year 2 (maximum dose 40 mg). Patients originally randomized to placebo (P -> O) showed substantial reduction in TLV after treatment with OctLAR in Year 2 (Delta% -7.66 +/- 9.69%, P = 0.011). The initial reduction of TLV in the OctLAR group (O -> O) was maintained for 2 years (Delta% -5.96 +/- 8.90%), although did not change significantly during Year 2 (Delta% -0.77 +/- 6.82%). OctLAR inhibited renal enlargement during Year 1 (Delta% +0.42 +/- 7.61%) in the (O -> O) group and during Year 2 (Delta% -0.41 +/ 9.45%) in the (P -> O) group, but not throughout Year 2 (Delta% +6.49 +/- 7.08%) in the (O -> O) group. Using pooled analyses of all individuals who received OctLAR for 12 months, i.e. in Year 1 for O -> O patients and Year 2 for P -> O patients, average reduction in TLV was -6.08 +/- 7.58% (P = 0.001) compared to net growth of 0.9 +/- 8.35% in the original placebo group. OctLAR-treated individuals continued to experience improvements in QOL in Year 2, although overall physical and mental improvements were not significant during Year 2 compared to Year 1. Changes in GFR were similar in both groups. CONCLUSION: Over 2 years, OctLAR significantly reduced the rate of increase in TLV and possibly the rate of increase in TKV. PMID- 22773241 TI - Peritransplant management of retained native kidneys in autosomal dominant polycystic kidney disease. PMID- 22773242 TI - Extraglomerular C3 deposition and metabolic impacts in patients with IgA nephropathy. AB - BACKGROUND: The aim of the present study was to explore the significance of extraglomerular (Bowman's capsule and/or arteriole) C3 (ex-C3) deposits in IgA nephropathy (IgAN). METHODS: One hundred and seventy patients with IgAN were divided into two groups: Group A (n=79), patients who did not have ex-C3 deposits, and Group B (n=91), patients who had ex-C3 deposits. RESULTS: At the time of renal biopsy, Group B was characterized by a marked increase in diastolic blood pressure, total cholesterol, triglyceride and low-density lipoprotein cholesterol compared with those of Group A. After 4 years, the estimated glomerular filtration rate (eGFR) in Group B was significantly worse than that of Group A. Upon examination by electron microscopy, the arteriolar dense deposits in Group B were found to occur in significantly higher amounts than in Group A. One hundred and thirty-four patients underwent a 3-year follow-up study after intervention and were re-divided by therapeutic factors as follows: 'conventional therapy', treatment with anti-hypertensive drugs and/or anti-platelet drugs, and 'aggressive therapy', additional treatment with either tonsillectomy or corticosteroid. Patients treated with conventional therapy in Group B had significantly higher body mass index and levels of C3 and CH50 compared with other Groups. Aggressive therapy was significantly effective in urinary protein reduction in both Group A and Group B. Except for the patients who received aggressive therapy in Group A, the levels of the eGFR gradually declined. CONCLUSIONS: It appears that IgAN patients who have ex-C3 deposits have worse clinical outcomes. PMID- 22773243 TI - Pregnancy in CKD: whom should we follow and why? AB - BACKGROUND: Chronic kidney disease (CKD) has a high prevalence in pregnancy. In a period of cost constraints, there is the need for identification of the risk pattern and for follow-up. METHODS: Patients were staged according to K-DOQI guidelines. The analysis was prospective, January 2000-June 2011. Two hundred and forty-nine pregnancies were observed in 225 CKD patients; 176 singleton deliveries were recorded. The largest group encompasses stage 1 CKD patients, with normal renal function, in which 127 singleton deliveries were recorded. No hard outcomes occurred (death; dialysis); therefore, surrogate outcomes were analysed [caesarean section, prematurity, need for neonatal intensive care unit (NICU)]. Stage 1 patients were compared with normal controls (267 low-risk pregnancies followed in the same setting) and with patients with CKD stages 2-4 (49 singleton deliveries); two referral patterns were also analysed (known diagnoses; new diagnoses). RESULTS: The risk for adverse pregnancy rises significantly in stage 1 CKD, when compared with controls: odds ratios were caesarean section 2.73 (1.72-4.33); preterm delivery 8.50 (4.11-17.57); NICU 16.10 (4.42-58.66). The risks rise in later stages. There is a high prevalence of new CKD diagnosis (overall: 38.6%; stage 1: 43.3%); no significant outcome difference was found across the referral patterns. Hypertension and proteinuria are confirmed as independent risk factors. CONCLUSIONS: CKD is a risk factor in pregnancy; all patients should be followed within dedicated programmes from stage 1. There is need for dedicated interventions and educational programmes for maximizing the diagnostic and therapeutic potentials in early CKD stages. PMID- 22773244 TI - Fluctuation-induced dynamics of multiphase liquid jets with ultra-low interfacial tension. AB - Control of fluid dynamics at the micrometer scale is essential to emulsion science and materials design, which is ubiquitous in everyday life and is frequently encountered in industrial applications. Most studies on multiphase flow focus on oil-water systems with substantial interfacial tension. Advances in microfluidics have enabled the study of multiphase flow with more complex dynamics. Here, we show that the evolution of the interface in a jet surrounded by a co-flowing continuous phase with an ultra-low interfacial tension presents new opportunities to the control of flow morphologies. The introduction of a harmonic perturbation to the dispersed phase leads to the formation of interfaces with unique shapes. The periodic structures can be tuned by controlling the fluid flow rates and the input perturbation; this demonstrates the importance of the inertial effects in flow control at ultra-low interfacial tension. Our work provides new insights into microfluidic flows at ultra-low interfacial tension and their potential applications. PMID- 22773245 TI - The clinical features and prognosis of phyllodes tumors: a single institution experience in Taiwan. AB - BACKGROUND AND OBJECTIVES: The aim of this study was to document the clinical and pathological features of a single institutional series of Asian patients with phyllodes tumors, and to determine the prognosis, the adequate management and the predictive histological features. METHODS: The clinical data were retrospectively studied from the medical records and the pathological data from the Department of Pathology were utilized to identify 33 patients diagnosed with phyllodes tumors between 2003 and 2010. RESULTS: Eight patients had benign tumors, 13 borderline and 12 malignant. Nine patients (27 %) had recurrence. No patients classified as benign phyllodes tumors had recurrence, but those with malignant phyllodes tumors had a high recurrence rate (41 %). The 5-year disease-free survival was 59 %. The 5-year overall survival was 81 %. The width of surgical margin was not related to disease recurrence and stromal overgrowth was the only prognostic factor in terms of disease-free survival and overall survival. CONCLUSIONS: The phyllodes tumors of borderline and malignant classification in Asian patients had a high recurrence rate. Clinical and pathological factors, except for stromal overgrowth, cannot predict disease recurrence. Further molecular research is warranted. PMID- 22773247 TI - Unusual presentation of congenital cystic adenomatoid malformation of the lung. PMID- 22773246 TI - Characterisation of the T cell and dendritic cell repertoire in a murine model of mucopolysaccharidosis I (MPS I). AB - BACKGROUND: Mucopolysaccharidosis I (MPS I) is a metabolic disorder caused by alpha-L-Iduronidase (IDUA) deficiency, resulting in lysosomal accumulation of heparan (HS) and dermatan sulphate (DS). This has been reported in microglia, yet currently the effect of IDUA deficiency on T cells and dendritic cells (DC) and their functionality in disease pathogenesis remains unclear. METHODS: Peripheral blood was collected from 3 month old C57BL/6 MPS I (n = 11) and wildtype (WT) (n = 6) mice. T cell and DC phenotype and functional characteristics were identified by flow cytometry. RESULTS: MPS I mice exhibited a reduction in DC (p = <0.001) along with CD8+ cytotoxic (p = 0.01) and CD4+ T helper (p = 0.032) cells, compared to WT controls. MPS I DC displayed a significant decrease in cell surface CD123 (p = 0.02) and CD86 (p = 0.006) expression. Furthermore, CD45RB expression was significantly reduced on T helper cells in the MPS I population (p = 0.019). CONCLUSION: We report a reduction in circulating DC and T cells in the MPS I mouse; indicative of adaptive immune dysfunction. DC reduction may occur in response to down-regulation of the IL-3 receptor (CD123), necessary for DC survival. We also report down-regulation of cell surface CD86, a molecule required for T cell co-stimulation. T helper cell down-regulation of CD45RB is redolent of an anti-inflammatory phenotype with poor proliferative capacity. The definitive causes of our findings and the consequences and role that these findings play in the pathogenesis of MPS are unclear, but may be in response to lysosomal storage of unmetabolized HS and DS. PMID- 22773248 TI - Effect of continuous positive airway pressure on hemoglobin A(1c) in patients with obstructive sleep apnea: a systematic review and meta-analysis. AB - BACKGROUND: There is little conclusive data regarding the effect of continuous positive airway pressure (CPAP) on glycated hemoglobin (HbA(1c)). An earlier meta analysis included two randomized controlled trials (RCTs) and found no significant effect of CPAP on HbA(1c). The meta-analysis presented here was conducted to include all relevant observational studies and RCTs on the effect of CPAP on HbA(1c). METHODS: We searched the PubMed database for all studies published prior to March 2012 for trials of the effect of CPAP on HbA(1c). Data from observational studies and RCTs that met the inclusion criteria were extracted for pre- and post-treatment HbA(1c). RESULTS: A total of nine studies that included 151 subjects met the inclusion criteria. The duration of the studies ranged from 41 days to 6 months. The mean net change in the HbA(1c) was 0.06 % [95 % CI: -0.24, 0.12] (p = 0.5). Five of the nine studies, with a total of 112 subjects, comprised patients with diabetes mellitus (DM) type 2. The mean net change in HbA(1c) for the subjects with DM type 2 was 0.08 % [95 % CI: -0.26, 0.42] (p = 0.65). The mean net change in HbA(1c) for subjects with DM type 2 in studies that were at least 3 months in duration was 0.16 % [95 % CI: -0.26, 0.58] (p = 0.45). CONCLUSIONS: This meta-analysis found that CPAP does not reduce HbA(1c) levels when used in the short term. PMID- 22773249 TI - Effect of smoking and gender on pulmonary function and clinical features in sarcoidosis. AB - BACKGROUND: The effect of cigarette smoking on the clinical manifestations and progression of sarcoidosis is not well characterized. We sought to determine the effects of smoking in sarcoidosis patients and to evaluate for gender-specific differences. METHODS: We examined the effects of cigarette smoking in 518 patients seen at the Sarcoidosis and Interstitial Lung Disease Center at Wayne State University using radiographic pattern, pulmonary function testing, and clinical features of the disease. We performed a separate analysis to evaluate for gender-specific differences based on smoking history. RESULTS: We found that smokers had significantly lower FEV(1) and FEV(1)/FVC values. Total lung capacity was not significantly different between smokers and nonsmokers, but diffusion capacity for carbon monoxide (DL(CO)) was significantly reduced in smokers. Gender-based statistical analysis showed a marked decrease in DL(CO) values among female smokers. Smokers were also found to have a higher incidence of extrapulmonary involvement as multivariate regression analysis demonstrated that both smoking and female gender are significantly associated with the development of extrapulmonary manifestations. CONCLUSIONS: Our data indicate that both cigarette smoking and gender are important in shaping the clinical manifestations of sarcoidosis. The nature of the gender difference requires further study and may be related to differences in inflammatory response. PMID- 22773250 TI - Issues concerning the evaluation and regulation of predictive genetic testing. AB - This paper is a precis of my keynote address at the Symposium on Predictive Genetic Testing organised by the Robert Koch Institute in Berlin. The talk is based on reflections which I have had over a number of years on genetic testing and its evaluation and regulation. It presents a thesis, which I hope will generate discussion and comment. A theme which will run through the paper is the need for precise definition of terms before making any normative statement about such terms. Our failure to do so in genetic discourse is at best confusing and at worst capable of resulting in inappropriate (and sometimes harmful) regulatory responses. PMID- 22773251 TI - Association of P2Y(2) receptor SNPs with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients. AB - The P2Y(2) receptor is a G-protein-coupled receptor with adenosine 5' triphosphate (and UTP) as natural ligands. It is thought to be involved in bone physiology in an anti-osteogenic manner. As several non-synonymous single nucleotide polymorphisms (SNPs) have been identified within the P2Y(2) receptor gene in humans, we examined associations between genetic variations in the P2Y(2) receptor gene and bone mineral density (BMD) (i.e., osteoporosis risk), in a cohort of fracture patients. Six hundred and ninety women and 231 men aged >=50 years, visiting an osteoporosis outpatient clinic at Maastricht University Medical Centre for standard medical follow-up after a recent fracture, were genotyped for three non-synonymous P2Y(2) receptor gene SNPs. BMD was measured at three locations (total hip, lumbar spine, and femoral neck) using dual-energy X ray absorptiometry. Differences in BMD between different genotypes were tested using analysis of covariance. In women, BMD values at all sites were significantly different between the genotypes for the Leu46Pro polymorphism, with women homozygous for the variant allele showing the highest BMD values (0.05 > p > 0.01). The Arg312Ser and Arg334Cys polymorphisms showed no differences in BMD values between the different genotypes. This is the first report that describes the association between the Leu46Pro polymorphism of the human P2Y(2) receptor and the risk of osteoporosis. PMID- 22773253 TI - Effects of robot-assisted therapy on stroke rehabilitation in upper limbs: systematic review and meta-analysis of the literature. AB - We systematically reviewed and analyzed the literature to find randomized controlled trials (RCTs) that employed robotic devices in upper-limb rehabilitation of people with stroke. Out of 574 studies, 12 matching the selection criteria were found. The Fugl-Meyer, Functional Independence Measure, Motor Power Scale, and Motor Status Scale outcome measures from the selected RCTs were pooled together, and the corresponding effect sizes were estimated. We found that when the duration/intensity of conventional therapy (CT) is matched with that of the robot-assisted therapy (RT), no difference exists between the intensive CT and RT groups in terms of motor recovery, activities of daily living, strength, and motor control. However, depending on the stage of recovery, extra sessions of RT in addition to regular CT are more beneficial than regular CT alone in motor recovery of the hemiparetic shoulder and elbow of patients with stroke; gains are similar to those that have been observed in intensive CT. PMID- 22773252 TI - Tuberculosis: finding a new potential antimycobacterium derivative in a aldehyde arylhydrazone-oxoquinoline series. AB - Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis, which remains a serious public health problem. The emergence of resistant bacterial strains has continuously increased and new treatment options are currently in need. In this work, we identified a new potential aldehyde arylhydrazone-oxoquinoline derivative (4e) with interesting chemical structural features that may be important for designing new anti-TB agents. This 1-ethyl-N' [(1E)-(5-nitro-2-furyl)methylene]-4-oxo-1,4-dihydroquinoline-3-carbohydrazide (4e) presented an in vitro active profile against M. tuberculosis H37Rv strain (minimum inhibitory concentration, MIC = 6.25 MUg/mL) better than other acylhydrazones described in the literature (MIC = 12.5 MUg/mL) and close to other antitubercular agents currently on the market. The theoretical analysis showed the importance of several structural features that together with the 5-nitro-2 furyl group generated this active compound (4e). This new compound and the analysis of its molecular properties may be useful for designing new and more efficient antibacterial drugs. PMID- 22773254 TI - Review of hybrid exoskeletons to restore gait following spinal cord injury. AB - Different approaches are available to compensate gait in persons with spinal cord injury, including passive orthoses, functional electrical stimulation (FES), and robotic exoskeletons. However, several drawbacks arise from each specific approach. Orthotic gait is energy-demanding for the user and functionally ineffective. FES uses the muscles as natural actuators to generate gait, providing not only functional but also psychological benefits to the users. However, disadvantages are also related to the early appearance of muscle fatigue and the control of joint trajectories. Robotic exoskeletons that provide joint moment compensation or substitution to the body during walking have been developed in recent years. Significant advances have been achieved, but the technology itself is not mature yet because of many limitations related to both physical and cognitive interaction as well as portability and energy-management issues. Meanwhile, the combination of FES technology and exoskeletons has emerged as a promising approach to both gait compensation and rehabilitation, bringing together technologies, methods, and rehabilitation principles that can overcome the drawbacks of each individual approach. This article presents an overview of hybrid lower-limb exoskeletons, related technologies, and advances in actuation and control systems. Also, we highlight the functional assessment of individuals with spinal cord injury. PMID- 22773255 TI - Extraterritorial temperature pain threshold abnormalities in subjects with healed thermal injury. AB - Approximately 1.25 million individuals sustain burn injuries annually in the United States. Pain is frequent in patients with burn injuries and is often refractory to pharmacotherapy. We report quantitative sensory data from five subjects who sustained external thermal injuries to their limb(s) 8 weeks to 11 years previously, demonstrating reduced thermal pain thresholds in regions outside the burn injury zone, including contralateral limbs. Warm and cold detection thresholds were not significantly different from controls. These results complement data from animal models that demonstrate that allodynia can develop contralateral to a focal burn injury as a result of changes within the spinal cord and suggest that systemic or central mechanisms contribute to pain after burn injury. PMID- 22773256 TI - Efficiency of voluntary opening hand and hook prosthetic devices: 24 years of development? AB - Quantitative data on the mechanical performance of upper-limb prostheses are very important in prostheses development and selection. The primary goal of this study was to objectively evaluate the mechanical performance of adult-size voluntary opening (VO) prosthetic terminal devices and select the best tested device. A second goal was to see whether VO devices have improved in the last two decades. Nine devices (four hooks and five hands) were quantitatively tested (Hosmer model 5XA hook, Hosmer Sierra 2 Load VO hook, RSL Steeper Carbon Gripper, Otto Bock model 10A60 hook, Becker Imperial hand, Hosmer Sierra VO hand, Hosmer Soft VO hand, RSL Steeper VO hand, Otto Bock VO hand). We measured the pinch forces, activation forces, cable displacements, mass, and opening span and calculated the work and hysteresis. We compared the results with data from 1987. Hooks required lower activation forces and delivered higher pinch forces than hands. The activation forces of several devices were very high. The pinch forces of all tested hands were too low. The Hosmer model 5XA hook with three bands was the best tested hook. The Hosmer Sierra VO hand was the best tested hand. We found no improvements in VO devices compared with the data from 1987. PMID- 22773257 TI - Metabolic analysis of male servicemembers with transtibial amputations carrying military loads. AB - For servicemembers who have sustained amputations and wish to return to Active Duty, performing common military tasks is essential. The purpose of this study was to examine the metabolic requirements of servicemembers with transtibial amputations wearing a loaded rucksack and walking at a steady speed. We tested 12 servicemembers with unilateral transtibial amputations and 12 uninjured controls on a treadmill at two walking speeds (1.34 and 1.52 m/s) while they carried a 32.7 kg load. Oxygen consumption was recorded. Results showed that metabolic demand for the injured servicemembers was significantly higher (8.5% at 1.34 m/s and 10.4% at 1.52 m/s) than for controls. An understanding of energy expended during load carriage by this study population is critical for decisions regarding return-to-duty requirements. Although significant differences existed between uninjured controls and those with amputations, it is important to note that those differences are less than previously published. This finding, coupled with the fact that servicemembers with transtibial amputations have redeployed, implies that, despite statistical significance, results may not be clinically relevant. Future work should include more taxing conditions to identify a threshold for potential limitations. PMID- 22773258 TI - Initial developmental process of a VA semistructured clinical interview for TBI identification. AB - Identification of a remote traumatic brain injury (TBI), particularly mild TBI, is a challenge. The acknowledged standard for determining a history of prior TBI is self-report elicited through a structured or in-depth clinical interview. In April 2007, the Veterans Health Administration (VHA) mandated that the four section TBI Clinical Reminder screening instrument be completed on all individuals returning from deployment in the Operation Iraqi Freedom/Operation Enduring Freedom theaters of operation (VHA Directive 2007-013). If positive, a follow-up Second Level TBI Evaluation is to be completed. For validation studies of the TBI Clinical Reminder screening process and with the long-term goal of providing a structured methodology to complete the TBI history portion of the Second Level TBI Evaluation, we sought to develop a "criterion standard" semistructured clinical TBI identification interview. This tool was developed through consultation with TBI subject matter experts and built on the strengths of existing tools in the literature. This article describes the six-step developmental methodology and presents the resulting semistructured interview and accompanying manual. PMID- 22773259 TI - Computer-adaptive test to measure community reintegration of Veterans. AB - The Community Reintegration of Injured Service Members (CRIS) measure consists of three scales measuring extent of, perceived limitations in, and satisfaction with community reintegration. Length of the CRIS may be a barrier to its widespread use. Using item response theory (IRT) and computer-adaptive test (CAT) methodologies, this study developed and evaluated a briefer community reintegration measure called the CRIS-CAT. Large item banks for each CRIS scale were constructed. A convenience sample of 517 Veterans responded to all items. Exploratory and confirmatory factor analyses (CFAs) were used to identify the dimensionality within each domain, and IRT methods were used to calibrate items. Accuracy and precision of CATs of different lengths were compared with the full item bank, and data were examined for differential item functioning (DIF). CFAs supported unidimensionality of scales. Acceptable item fit statistics were found for final models. Accuracy of 10-, 15-, 20-, and variable-item CATs for all three scales was 0.88 or above. CAT precision increased with number of items administered and decreased at the upper ranges of each scale. Three items exhibited moderate DIF by sex. The CRIS-CAT demonstrated promising measurement properties and is recommended for use in community reintegration assessment. PMID- 22773260 TI - Computer-socket manufacturing error: how much before it is clinically apparent? AB - The purpose of this research was to pursue quality standards for computer manufacturing of prosthetic sockets for people with transtibial limb loss. Thirty three duplicates of study participants' normally used sockets were fabricated using central fabrication facilities. Socket-manufacturing errors were compared with clinical assessments of socket fit. Of the 33 sockets tested, 23 were deemed clinically to need modification. All 13 sockets with mean radial error (MRE) greater than 0.25 mm were clinically unacceptable, and 11 of those were deemed in need of sizing reduction. Of the remaining 20 sockets, 5 sockets with interquartile range (IQR) greater than 0.40 mm were deemed globally or regionally oversized and in need of modification. Of the remaining 15 sockets, 5 sockets with closed contours of elevated surface normal angle error (SNAE) were deemed clinically to need shape modification at those closed contour locations. The remaining 10 sockets were deemed clinically acceptable and not in need modification. MRE, IQR, and SNAE may serve as effective metrics to characterize quality of computer-manufactured prosthetic sockets, helping facilitate the development of quality standards for the socket manufacturing industry. PMID- 22773261 TI - Obstacle course: users' maneuverability and movement efficiency when using Otto Bock C-Leg, Otto Bock 3R60, and CaTech SNS prosthetic knee joints. AB - The performance and movement efficiency of prosthesis users while traversing a multisectional obstacle course (OC) were evaluated using a crossover design with random allocation of three prosthetic knee joints: the SNS (CaTech; Dayton, Ohio) the C-Leg (Otto Bock; Duderstadt, Germany), and the 3R60 (Otto Bock). Twelve users completed the OC twice with each joint, once without and once with a mental loading task (MLT). The performance was objectively assessed using time measurement from digital video recordings, and the Total Heart Beat Index was used to estimate movement efficiency. A 1 mo familiarization period was provided for each knee joint before data collection. It took longer to complete the OC with the 3R60 compared with either the SNS or the C-Leg. No significant time differences were found between the C-Leg and the SNS, but differences between the 3R60 and the SNS (slalom and rock sections) and between the 3R60 and the C-Leg (rock section) were observed. Within the simulated sand section, two participants fell with the C-Leg, one with the 3R60, and none with the SNS. Movement efficiency without MLT was similar between all joints, but with an MLT a significant decrease in movement efficiency was observed with the C-Leg. Previous experience using an SNS had no influence on the results. PMID- 22773262 TI - Application of self-report and performance-based outcome measures to determine functional differences between four categories of prosthetic feet. AB - We examined the application of outcome measures to determine changes in function caused by standardized functional prosthetic gait training and the use of four different prosthetic feet in people with unilateral transtibial limb loss. Two self-report measures (Prosthetic Evaluation Questionnaire-Mobility Scale [PEQ-13] and Locomotor Capabilities Index [LCI]), and three performance-based measures (Amputee Mobility Predictor with a prosthesis [AMPPRO], 6-minute walk test [6MWT] and step activity monitor [SAM]) were used. Ten people with unilateral transtibial limb loss, five with peripheral vascular disease (PVD) and five without PVD, completed testing. Subjects were tested at baseline and after receiving training with their existing prosthesis and with the study socket and four prosthetic feet, i.e., SACH (solid ankle cushion heel), SAFE (stationary attachment flexible endoskeletal), Talux, and Proprio feet, over 8 to 10 weeks. Training was administered between testing sessions. No differences were detected by the PEQ-13, LCI, 6MWT, or SAM following training and after fitting with test feet. The AMPPRO demonstrated differences following training with the existing prosthesis in the PVD group and between selected feet from baseline testing ( p 20 min and/or an obstructive washout curve pattern during the diuretic phase. We studied the longitudinal changes in SFU hydronephrosis grade and uEGF in each group and compared concentration levels at three time points in both groups. The enzyme-linked immunosorbent assay (ELISA) method was used to measure EGF concentrations in the urine. The results were normalized with urinary creatinine (Cr). RESULTS: During the first 6 months, from 6 to 12 months, and in the second year of life, median SFU hydronephrosis grade and uEGF levels were 2, 2 (p = 0.015), and 1 (p < 0.01), and 50, 59 (p = 0.015), and 69.5 ng/mg Cr (p < 0.01), respectively, in the observational group. In the first 6 months, preoperatively and at 3-12 months postoperatively, the median SFU hydronephrosis grade and uEGF levels were 4, 4, and 3 (p > 0.05), and 38, 46, (p > 0.05), and 55 ng/mg Cr (p < 0.01), respectively, in the surgical group. uEGF levels in the first 6 months of life were significantly lower in the surgical group than in the observational group (p < 0.01). Patients in the observational group with SFU grade 3-4 hydronephrosis showed higher uEGF levels than those in the surgical group with SFU grade 3-4 in (p = 0.048). CONCLUSIONS: Urinary EGF changes over time are associated with inverse changes in SFU hydronephrosis grade, which suggests a role for uEGF as a predictive marker of worsening hydronephrosis grades in infants with ANH. uEGF in the first 6 months of life may predict the need for surgery in infants with ANH. PMID- 22773266 TI - Downregulation of MiR-93 expression reduces cell proliferation and clonogenicity of HepG2 cells. AB - BACKGROUND/AIMS: MiR-93 was observed in various types of cancers. This study is to investigate a role of miR-93 in the carcinogenesis of HCC. METHODOLOGY: The expression of miR-93 in HepG2 cells and prima-ry human hepatocytes (PHHC) was measured by RT-PCR. HepG2 cells were transfected with miR-93 inhibitor or negative control. The cell proliferation was determined by using the CellTiter 96(r) Aqueous One Solution Cell Proliferation Assay kit. The migration and clonogenicity in vitro were measured by cell migration assay, colony formation analysis and anchorage-in-dependent growth assay. The apoptosis and cell cycle were detected by flow cytometry analysis. The mRNA and protein levels of transforming growth factor-beta type II receptor (TGFBR2) and integrin beta8 (ITGB8)were evaluated by RT-PCR and western blot analysis. RESULTS: MiR-93 was upregulated in HepG2 cells compared with PHHC and inhibition of miR-93 significantly suppressed HepG2 cell proliferation, migration and col-ony formation. The expressions of TGFBR2 and ITGB8 were upregulated when miR-93 was inhibited. CONCLUSIONS: Our results reveal an important contribution for miR-93 in hepatocarcinogenesis and suggest a role for TGFBR2 and ITGB8 dysregulation in this process. Thus,the use of synthetic inhibitor of miR-93 may prove to bea promising approach to liver cancer treatment. PMID- 22773268 TI - Hybrid functionals and GW approximation in the FLAPW method. AB - We present recent advances in numerical implementations of hybrid functionals and the GW approximation within the full-potential linearized augmented-plane-wave (FLAPW) method. The former is an approximation for the exchange-correlation contribution to the total energy functional in density-functional theory, and the latter is an approximation for the electronic self-energy in the framework of many-body perturbation theory. All implementations employ the mixed product basis, which has evolved into a versatile basis for the products of wave functions, describing the incoming and outgoing states of an electron that is scattered by interacting with another electron. It can thus be used for representing the nonlocal potential in hybrid functionals as well as the screened interaction and related quantities in GW calculations. In particular, the six dimensional space integrals of the Hamiltonian exchange matrix elements (and exchange self-energy) decompose into sums over vector-matrix-vector products, which can be evaluated easily. The correlation part of the GW self-energy, which contains a time or frequency dependence, is calculated on the imaginary frequency axis with a subsequent analytic continuation to the real axis or, alternatively, by a direct frequency convolution of the Green function G and the dynamically screened Coulomb interaction W along a contour integration path that avoids the poles of the Green function. Hybrid-functional and GW calculations are notoriously computationally expensive. We present a number of tricks that reduce the computational cost considerably, including the use of spatial and time reversal symmetries, modifications of the mixed product basis with the aim to optimize it for the correlation self-energy and another modification that makes the Coulomb matrix sparse, analytic expansions of the interaction potentials around the point of divergence at k = 0, and a nested density and density-matrix convergence scheme for hybrid-functional calculations. We show CPU timings for prototype semiconductors and illustrative results for GdN and ZnO. PMID- 22773269 TI - Enhanced N-glycosylation site exploitation of sialoglycopeptides by peptide IPG IEF assisted TiO2 chromatography. AB - Playing an important role in a broad range of biological and pathological processes, sialylation has been drawing wide interest. The efficient sialoglycopeptides enrichment methods are therefore attracting considerable attention. In this paper, we first compared two conventional enrichment methods, lectin and TiO(2), and analyzed their characteristics. Furthermore, considering the highly negatively charged nature of sialic acids, we developed a new strategy, peptide immobilized pH gradient isoelectric focusing (IPG-IEF) assisted TiO(2) chromatography (PIAT), for the highly efficient enrichment of sialoglycopeptides. In this method, peptides were first separated into 24 fractions using peptide IPG-IEF. Sialoglycopeptides were relatively concentrated in low-pH fractions of the immobilized pH strips and were captured using TiO(2) chromatography. As a result, 614 N-glycosylation sites were identified in 582 sialoglycopeptides within 322 sialoglycoproteins from rat liver using PIAT. To our knowledge, this work represents one of the most comprehensive sialoglycoproteomic analyses in general and exhibits the largest database of sialoglycoproteome in rat liver currently. So the new strategy introduced here exhibits high efficiency and universality in the sialoglycopeptide enrichment, and is a powerful tool for sialoglycoproteome exploration. PMID- 22773270 TI - Electroencephalographic hypersynchrony in a child with night terrors. PMID- 22773271 TI - Cerebrovascular pulsatility in patients with sleep-disordered breathing. AB - PURPOSE: The aim of our study is to determine the association between the pulsatility index (PI), a surrogate of cerebral small vessel disease and sleep disordered breathing (SDB). METHODS: We conducted a transcranial Doppler ultrasound (TCD) study of 19 consecutive patients free of stroke and cardiovascular disease, referred for the evaluation of SDB. TCD was performed by a certified technologist. Subsequent polysomnography was performed according to the practice parameters of the American Academy of Sleep Medicine. We evaluated the association between the apnea-hypopnea index (AHI), the oxygen nadir, the blood flow velocities, and the Gosling PI, for the middle cerebral artery. We performed Spearman's rank correlation and nonparametric regression to evaluate the relationship between AHI, oxygen levels, and the PI. RESULTS: Median age was 48 years (range 37-83), with 52 % male sex (n = 10), and median BMI of 29.9 (range 25-40.4). The median AHI was 16.4 (0.2-69). The median PI was 0.97 (0.72 1.89) cm/s. The PI correlated with the AHI (rho = 0.44; p = 0.004) and with age (rho = 0.57; p = 0.001). Nonparametric regression adjusting for age showed a positive association between the AHI and the PI (standardized estimate = 0.88; p = 0.002). There was no relation between the oxygen nadir and the PI. CONCLUSION: We observed increased PI in patients with SDB during wakefulness. The PI could potentially be an estimate of cerebral small vessel disease in patients with SDB and hence allow evaluating cerebral hemodynamics during wakefulness with a clinically relevant device. PMID- 22773272 TI - The spirits of capitalism and christianity and their impact on the formation of healthcare leaders. AB - In this article, I portray how the ethos of Christianity, broadly speaking, and the mores of capitalism intersect in the formation of healthcare leaders and the difficult decisions they make in insuring the viability of healthcare institutions. More particularly, I argue that healthcare leaders in Christian healthcare institutions are largely formed by and dependent on a capitalistic ethos in making decisions and less so by a Christian ethos. There are key differences in these two meaning systems, and these differences, in part, reveal an incompatibility between them. This incompatibility does not imply a rejection of capitalism, if that is even possible, but rather a recognition of its effects and limits vis-a-vis the formation of healthcare leaders and their decision making process. Finally, I offer an approach that deals with the spirits of capitalism and Christianity in forming healthcare leaders and their decision making. PMID- 22773273 TI - Can subclavian blood be equated with a peripheral blood sample? A series of 50 cases. AB - If femoral blood is not available at autopsy, toxicological analyses, in particular blood ethanol measurements, are carried out on cardiac blood. This is known to be subject to major redistribution. We aimed to determine whether subclavian blood can be equated with a peripheral blood sample and could be used if femoral blood is not available. The study was based on 50 medicolegal autopsies in which we compared ethanol concentrations between subclavian blood, the different heart blood compartments (right and left cardiac blood), and femoral blood. Mechanisms that could lead to variations in concentration, i.e., postmortem redistribution and/or endogenous production, were also taken into account in interpreting the results. Ethanol concentrations were determined by headspace gas chromatography with a flame ionization detector. In each case, we recorded the circumstances of death, resuscitation attempts if any, degree of putrefaction, chest or abdominal trauma, and/or inhalation of gastric fluid in the airways. Ethanol concentrations in subclavian blood were found to be close to those in peripheral blood (p = 0.948) and were not influenced by the degree of putrefaction (r = 0.017, p = 0.904), gastric ethanol concentration (r = -0.011, p = 0.940), inhalation of gastric contents in the airways (p = 0.461), or cardiac resuscitation attempts (p = 0.368). We discuss the possible explanations for these findings and stress the value of sampling subclavian blood when femoral blood is not obtainable at autopsy. PMID- 22773275 TI - Ionic rectification by electrostatically actuated tethers on single walled carbon nanotube membranes. AB - Large electrostatically actuating charged tethers (~2.5 nm) at the tip entrances of single walled carbon nanotubes (i.d. ~ 1.5 nm) can dramatically enhance ionic gating at the CNT core entrance. Significant rectification of small ions at physiological ionic strengths is observed and this system closely mimics the function of protein channels. PMID- 22773274 TI - Postmortem biochemical investigations in hypothermia fatalities. AB - Despite the progress made during the past several decades in forensic pathology, the possibilities for the postmortem diagnosis of hypothermia remains relatively limited. Aside from histology and immunohistochemistry, numerous authors have investigated the postmortem biochemistry of hypothermia fatalities. Several biochemical markers (e.g., glucose, electrolytes, hormones, ketone bodies, and neurotransmitters) and various biological samples (e.g., blood, urine, heart, liver, skeletal muscle as well as pericardial and cerebrospinal fluids) have been proposed as potentially useful markers to improve the insufficient diagnostic efficacy of macroscopic and microscopic findings. The aim of this article is to review the medicolegal literature covering the postmortem biochemical investigations that are associated with hypothermia cases as well as report our own research results on this topic where possible. PMID- 22773276 TI - Chemoembolization and radioembolization for metastatic disease to the liver: available data and future studies. AB - Hepatic metastatic disease includes tumors from colorectal, neuroendocrine, breast, melanocytes, kidney, and other primary sites. Tumor characteristic, liver function, and performance status are factors that need to be considered while deciding on treatment. Surgery offers the most optimal therapeutic option for such patients. However, due to the diffuse nature of disease and large tumor burden, a majority of the patients are not operable. Moreover, because the morbidity and mortality is associated with hepatic metastatic disease, it is intuitive to investigate and develop treatment options that target the tumor locally, thereby minimizing systemic toxicities. Transarterial locoregional therapies, such as chemoembolization and radioembolization, have been widely investigated during the past decade for the treatment of hepatic metastatic disease and have generated encouraging outcomes in term of survival, response, and quality of life. Moreover, these options are applicable in many clinical scenarios, because they are less limited by tumor characteristics. Currently, a large number of trials are investigating the combination of locoregional and systemic therapies, and the results are expected to benefit the treating physicians and patients alike. PMID- 22773278 TI - Concentration and the second stage of labor: outcomes associated with the interactive metronome. AB - OBJECTIVE: To analyze the association between concentration, as measured by the Interactive Metronome, and a prolonged second stage of labor in nulliparous patients. STUDY DESIGN: From September 2008 to November 2009, nulliparous women at >=34 weeks' gestation who were planning to use an epidural were asked to perform a 1-minute Interactive Metronome clapping test. Scores and demographic information were recorded. Data were then abstracted regarding each patient's labor course. The main outcome measure was the frequency of the second stage of labor exceeding 2 hours. Only patients with epidural anesthesia who completed the second stage of labor and did not require operative delivery performed for fetal indications prior to 2 full hours of pushing were included. RESULTS: Of the patients whose Interactive Metronome test scores were in the last quartile, which we associated with poor concentration, 52.9% (18/34) had a second stage of labor exceeding 2 hours compared with only 31.7% (33/104) of patients whose scores placed them in the first three quartiles (p = 0.026). CONCLUSION: Nulliparous patients with poor concentration scores, as measured by the Interactive Metronome, were more likely to push greater than 2 hours in the second stage of labor. PMID- 22773277 TI - Relative survival of patients with supratentorial low-grade gliomas. AB - We sought to assess the population-based estimates of age-standardized survival among patients with low-grade gliomas (LGG) and to determine the impact of age and time on relative survival (RS). Data from the Surveillance, Epidemiology, and End Results (SEER) program of NCI from 1973 through 2006 were analyzed to assess survival among 5037 patients. Relationships were modeled using Dickman's piecewise constant hazards RS model. The 3- and 10-year age-standardized RS were 67% and 37%, respectively. When analyzed by age group, the 10-year overall survival (OS) and RS for children (age, <16 years), young adults (age, 16-39 years), adults (age, 40-64 years), and older patients (age, >=65 years) were 86% and 86%, 61% and 62%, 40% and 43%, and 10% and 14%, respectively. The observed difference between OS and RS was larger among older patients (4%) and smallest among children (<1%). Older patients were 30.5 times (excess hazard ratio [eHR]; 95% confidence interval [CI], 20.3-50.0) as likely as young adults to die during the first year and 18.2 times as likely to die during the second year. Adults were 5.3 (eHR; 95% CI, 3.5-8.1) times as likely to die during their first year as young adults. In the remaining years, the observed survival differences were substantially decreased, and the presence of an age-by-follow-up interaction was observed. Survival among older patients with LGG was substantially different from the one computed for young adults and children. Despite the hazards across age groups not being proportional, RS does not provide additional information, compared with OS, in patients with LGG. PMID- 22773279 TI - The safety of progesterone and 17-hydroxyprogesterone caproate administration for the prevention of preterm birth: an evidence-based assessment. AB - The safety of supplemental progestin therapy during pregnancy reflects whether an agent exclusively promotes or potentially inhibits progestational cellular functions and whether treatment incites a metabolic derangement or other pathophysiology to initiate rare untoward events. No safety signal has been identified from intravaginal administration of natural progesterone from phase III clinical trials. The Food and Drug Administration has identified a legitimate safety signal regarding second-trimester miscarriage and stillbirth with exposure to 17-hydroxyprogesterone caproate (17-OHPC). Results from recent phase II and III trials in multiples also demonstrates concern with exposure to this synthetic for fetal loss and increased severe respiratory distress in neonates (one study each), as well as repeated significant associations for shorter duration of pregnancy and poorer fetal growth in others. The biological plausibility for 17 OHPC to be associated with adverse outcomes can be suggested from pharmacogenomic observations, ex vivo experimentation, and clinical observations. Further data are needed interrogating the potential for rare fetal or maternal adverse events/safety outcomes with exposure to progestins. Safety concerns should be incorporated into prescribing decisions. PMID- 22773280 TI - Effect of clinical and histological chorioamnionitis on the outcome of preterm infants. AB - Chorioamnionitis contributes to neonatal and maternal morbidity and mortality. We aimed to evaluate of the impact of clinical and histological chorioamnionitis on mortality and morbidity of preterm infants. Maternal and neonatal data were collected in a retrospective cohort of preterm infants less than 30 weeks' gestation. Infants were divided into three groups: those born to mothers with clinical chorioamnionitis, histological chorioamnionitis, or no chorioamnionitis. Of 274 identified preterm infants, 33 infants were born to mothers with clinical chorioamnionitis, 95 to mothers with histological chorioamnionitis, and 146 to mothers with no chorioamnionitis. Data were available for 180 (78%) of the 230 survivors at 18 months corrected age. Infants in the study groups were similar in gestational age, birth weight, and sex distribution. Clinical and histological chorioamnionitis were not predictive of infant mortality, cerebral palsy, bronchopulmonary dysplasia, periventricular leukomalacia, or retinopathy of prematurity. Infants in the clinical chorioamnionitis group had significantly lower cognitive (88 +/- 10), language (82 +/- 12), and motor (89 +/- 11) scores compared with infants in the histological chorioamnionitis group (101 +/- 13, p < 0.01; 91 +/- 13, p < 0.05; and 99 +/- 13, p < 0.05, respectively) and to infants in the no chorioamnionitis group (99 +/- 13, p < 0.01; 92 +/- 15, p < 0.05; and 97 +/- 13, p < 0.05, respectively). Clinical chorioamnionitis is associated with developmental delay in preterm infants despite adequate treatment. PMID- 22773281 TI - The relative proportion of preterm births complicated by premature rupture of membranes in multifetal gestations: a population-based study. AB - OBJECTIVE: To compare the relative contribution of premature rupture of membranes (PROM) to preterm births in singleton compared with multifetal gestations. STUDY DESIGN: A population-based retrospective cohort study of 291,782 nonanomalous live births in the state of Ohio from January 1, 2006, to December 31, 2007, identified through birth certificate data. Frequency of PROM was compared between singleton and multifetal gestations and then stratified by gestational age at birth. Multivariate regression analysis estimated the risk of PROM by plurality in each gestational age group, accounting for influential risk factors. RESULTS: The frequency of PROM increased with increasing plurality of gestation. The relative proportion of preterm birth < 37 weeks complicated by PROM increased with gestational plurality 13.2% singletons, 16.8% twins, 20.0% triplets, 19.6% quadruplets, and 100% for higher-order multiples (p < 0.001). The frequency of PROM increased with earlier gestational age at birth, regardless of plurality. The increased risk of PROM in multifetal gestation persisted even after adjustment for influential concomitant risk factors. CONCLUSION: The proportion of preterm birth attributable to PROM increases by plurality of gestation, with its most significant contribution in higher-order multiples and at earliest gestational ages when outcomes are the poorest. PMID- 22773282 TI - Lutein and zeaxanthin supplementation in preterm very low-birth-weight neonates in neonatal intensive care units: a multicenter randomized controlled trial. AB - BACKGROUND: Human milk feeding protects against oxidative stress-induced damage in preterm neonates, including severe multifactorial diseases such as retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD). The carotenoids, which are not found in formula milk, might play a key role in these actions. METHODS: A multicenter, double-blind, randomized controlled trial was conducted in three tertiary Italian neonatal intensive care units. All preterm infants < 32(+6) weeks' gestational age were eligible and were randomized to a single, oral, daily 0.5-mL dose of carotenoid supplementation (0.14 mg lutein + 0.0006 mg zeaxanthin) or placebo (5% glucose solution) from birth till 36 weeks' corrected gestational age. Primary outcomes were threshold ROP, NEC > second stage, and BPD. Surveillance for detection of these diseases and for intolerance/adverse effects was performed. RESULTS: No treatment-related adverse effect was documented in the 229 analyzed infants, whose clinical/demographical characteristics were similar in the two groups. Threshold ROP incidence did not significantly differ in treated (6.2%) versus not treated infants (10.3%; p = 0.18). The same occurred for NEC (1.7% versus 5.1%; p = 0.15) and BPD (4.5% versus 10.3%; p = 0.07). Noteworthy, the progression rate from early ROP stages to threshold ROP was decreased by 50% (0.30 versus 0.44; p = 0.23). CONCLUSION: Lutein/zeaxanthin supplementation in preterm infants is well tolerated. No significant effect was seen on threshold ROP, NEC, or BPD. The decreasing trends of these outcomes in the treatment group need to be assessed and confirmed on larger sample-sizes. PMID- 22773283 TI - Visual function in preterm infants without major retinopathy of prematurity or neurological complications. AB - OBJECTIVE: Early exposure of preterm infants to visual stimulation could affect the process of visual maturation. The aim of this study was to assess the impact of prematurity on visual function at 15 months post-term. SUBJECTS AND METHODS: Visual function was assessed in 102 preterm (PTI) and 50 full-term infants (FTI) without major cerebral pathology or retinopathy of prematurity (ROP) of grade 2 to 5, at 15 months' corrected age. The visual acuity, refractive status, contrast sensitivity, strabismus, fundus, and neurodevelopment were examined. RESULTS: Impairments of individual visual functions were 2 to 10 times more common in PTI than FTI. However, the difference was significant only for refractive errors (p = 0.007, odds ratio [OR] = 10.5). The incidence of visual deficits was higher in PTI with gestational age less than 32 weeks compared with PTI with higher gestational age (OR = 1.3 to 2.0), but not significantly. Of the PTI, 4.9%, 2.9%, and 10.8% had mild abnormalities on ultrasound scans, neuromotor, and developmental examination, respectively, which were not associated with increased incidence of visual deficits. CONCLUSION: Premature exposure to visual stimulation does not induce visual maturation but it is associated with impairment of certain aspects of visual function even in the absence of major ROP or neurodevelopmental deficits. PMID- 22773284 TI - Breast-feeding and responses to infant vaccines: constitutional and environmental factors. AB - Neonates and nursing infants are special with regard to immune development and vulnerability to infectious diseases. Although breast-feeding is essential to modulate and prime immune defenses, vaccines (an interventional prophylaxis) are crucial to prevent and control infectious diseases. During nursing, the type of feeding influences infants' natural defenses (including gut colonization) and their response to vaccines, both through cell-mediated immunity and specific antibody production. Given the variety and combination of vaccine components (antigens and excipients, preservative thimerosal, and aluminum adjuvants) and route of administration, there is a need to examine the role of infant feeding practices in intended and nonintended outcomes of vaccination. Maternal factors related to milk constituents (nutrients and pollutants) and feeding practices can affect response to vaccines. Collectively, studies that compared type of feeding (or used breast-feeding-adjusted statistical models) showed significant influence on some vaccines taken during infancy. Nurslings deprived of the full benefit of breast-feeding could have altered immune responses affecting vaccine outcome. In the absence of studies elucidating neurodevelopment (including excitoxicity) and immunotoxicity issues, vaccination practices should promote and support breast feeding. PMID- 22773285 TI - Routine probiotic use in very preterm infants: retrospective comparison of two cohorts. AB - OBJECTIVE: Evidence supports the efficacy of probiotics in reducing necrotizing enterocolitis (NEC) in very low-birth-weight infants, although concerns remain with regard to their routine use. Since 2008 in our neonatal intensive care unit, a low dose of probiotics (unique strain) is administered as standard of care in all preterm babies born at 24 to 31 weeks' gestation. This study reports outcomes in infants receiving probiotic cohort (PC) compared with the historical cohort. DESIGN: Treatment with Lactobacillus rhamnosus Lcr35 (Lcr Restituo) (2 * 108 colony-forming units/12 h) was started early after birth and intention to treat was up to 36 weeks' gestation. The main outcome was definite NEC. Secondary outcomes were mortality, late-onset sepsis (LOS), cholestasis, isolated rectal bleeding (IRB), and time to reach full enteral feeding (FEF). RESULTS: A total of 1130 patients were included. No adverse effects were observed. Infants in PC presented a reduced rate of NEC (odds ratio [OR] 0.20; 95% confidence interval [CI] 0.07 to 0.58), mortality (OR 0.46; 95% CI 0.21 to 1.00), and LOS (OR 0.60; 95% CI 0.40 to 0.89) and achieved FEF significantly earlier. IRB was significantly reduced among infants receiving the complete scheduled treatment. CONCLUSION: Administration of Lcr Restituo was well tolerated and associated with lower mortality and morbidities in this cohort. Our results provide evidence in support of the hypothesis that this probiotic may reduce IRB. PMID- 22773286 TI - Effect of antenatal treatment of maternal periodontitis on early childhood neurodevelopment. AB - OBJECTIVE: To determine if antenatal treatment of maternal periodontitis affects early childhood neurodevelopment. STUDY DESIGN: We evaluated neurodevelopment of 331 24-month-old children born to women who participated in a randomized trial of antenatal (167) or postpartum (164) treatment of periodontitis. Children within groups defined by maternal treatment were designated as high risk for abnormal neurodevelopment (n = 96; birth at <=34(6)/7 weeks' gestation or small for gestational age following birth at term) or low risk (n = 235; appropriate birth weight and >=37 weeks' gestation). We measured neurodevelopment using the Bayley Scale of Infant and Toddler Development III (BSID III) and neurological examination. Treatment effect was analyzed using a chi-square or Fisher exact test. Between-group mean scores were compared using Student t test. RESULTS: There were no differences in the incidence of neuromotor or sensory (visual or hearing) impairment or scores on the BSID III between groups. Low-risk children in the antenatal treatment group had higher language scores than those in the postpartum treatment group (92.9 versus 89.2; p = 0.05). CONCLUSION: Antenatal treatment of maternal periodontitis does not appear to affect neurodevelopment at 24 months of age. The slight improvement in language development in low-risk children may be an artifact or not clinically relevant. PMID- 22773287 TI - Retinopathy of prematurity in the Dominican Republic: challenges to screening and prevention. AB - OBJECTIVE: To determine the incidence of retinopathy of prematurity (ROP) in an intensive care nursery in the Dominican Republic and to identify factors that impact ROP outcomes, screening, and treatment. STUDY DESIGN: A database analysis was performed. The database was prospectively created by the pediatric ophthalmologist in a public maternity hospital in Santo Domingo during 2009. From January to December, all infants (n = 234) who received at least one ophthalmologic examination for ROP were included. ROP screening criteria were based upon: (1) American Academy of Pediatrics guidelines and (2) the presence of critical illness in larger, more mature infants at the discretion of the neonatologist. RESULTS: Overall, 22% were diagnosed with ROP and 4.3% had severe disease. Infants with ROP had a mean birth weight of 1452 g and a mean gestational age of 31 weeks, with 35% having a gestational age >32 weeks. In multivariable regression, only gestational age remained significant (0.8, 0.68 to 0.95). Twenty-two percent diagnosed with ROP did not complete all screening procedures. CONCLUSION: There are many challenges to preventing and treating ROP in the Dominican Republic. Increased awareness of the detrimental effects of hyperoxia, broader screening criteria, and an improved screening program will help to reduce visual impairment from ROP. PMID- 22773288 TI - Society of Maternal-Fetal Medicine annual meeting and a continuing medical education course: results of pre- and postcourse survey. AB - OBJECTIVE: To assess the influence of a continuing medical education (CME) course on knowledge acquired and potential to change clinical management or opinion. STUDY DESIGN: During the annual Society of Maternal-Fetal Medicine meeting, a survey consisting of 11 knowledge-based, 10 management plan, and 8 opinion questions was administered at the start and completion of the CME course. Chi square and Fisher exact test were used, and p < 0.05 was considered significant. RESULTS: The survey was administered electronically to 394 attendees. Questions assessing knowledge showed significant improvement with 91% (10/11) of queries. Purported management changed significantly with 60% (6/10) scenarios and opinions in 62% (5/8) of clinical situations. CONCLUSION: A survey done at the completion of a course indicates that CME improves knowledge and can change management and opinions. The prolonged benefits of CME need to be investigated. PMID- 22773289 TI - Maternal-fetal medicine workforce in the United States. AB - OBJECTIVE: To identify the current supply and locations of maternal-fetal medicine (MFM) subspecialists in active practice in the United States. STUDY DESIGN: This observational study examined the membership roster of the American Congress of Obstetricians and Gynecologists in 2010 for those whose practice was in either general obstetrics and gynecology or maternal-fetal medicine. Reliable national databases were used to determine the numbers and locations of births annually, reproductive-aged (15 to 44 years old) women, and level III perinatal centers in each state. RESULTS: There were 1355 MFM subspecialists in the United States in 2010 with the highest number being in the most populous states. Nearly all (98.2%) resided in metropolitan counties with level III perinatal center(s). Nationwide, there was one MFM subspecialist for every 24 general obstetrician gynecologists and for every 3150 births. States with the highest number of MFM subspecialists per 10,000 live births were Vermont (9.5), Connecticut (6.4), Maryland (5.8), New Jersey (5.7), Hawaii (5.7), and Massachusetts (5.6). The lowest densities were in Indiana (1.5), Mississippi (1.3), Idaho (1.2), and Arkansas (1.0), and North Dakota and Wyoming had none. CONCLUSION: Data from this population-level study will serve as a baseline to follow trends in the workforce of MFM practitioners. PMID- 22773290 TI - Neonatal effects of magnesium sulfate given to the mother. AB - OBJECTIVE: Magnesium historically has been used for treatment and/or prevention of eclampsia or preterm labor. More recently, antepartum magnesium sulfate has been suggested for prevention of cerebral palsy in preterm infants. Although adverse effects and toxicity of magnesium in pregnant women are well known, the fetal-neonatal effects of magnesium are less clear. The objective of this study was to evaluate the effects of magnesium on the newborn infant. STUDY DESIGN: This is a retrospective cohort analysis of women who received antepartum magnesium sulfate for prevention or treatment of eclampsia. Magnesium sulfate was given intravenously beginning with a 6-g dose, followed by 2- to 3-g/h infusion. Newborn hypotonia was diagnosed if an infant exhibited less than normal tone/activity upon admission to the nursery. RESULTS: Between January 2000 and February 2009, a total of 6654 women with preeclampsia were treated with intravenous magnesium sulfate as described; 88 (6%) of the infants were diagnosed with hypotonia. Lower 1-minute and 5-minute Apgar scores, intubation in the delivery room, admission to special care nursery, and hypotonia were all significantly increased as maternal serum magnesium concentrations increased before birth. CONCLUSION: Several neonatal complications are significantly related to increasing concentrations of magnesium in the maternal circulation. PMID- 22773291 TI - Physical therapy reduces bone resorption and increases bone formation in preterm infants. AB - AIM: To evaluate bone metabolism in newborn preterm infants before and after a physical therapy protocol. METHOD: This randomized controlled clinical trial included 30 newborn preterm infants with gestational age <= 35 weeks and appropriate weight for gestational age, who were randomized into control group (CG) and physiotherapy group (PG). The PG protocol consisted of 15 minutes of daily passive movements with gentle joint compression 5 days a week. Daily data were obtained on feeding and body weight. Measurements of bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD) were collected before and after intervention in both groups. The analysis of covariance test was performed to compare the means of both groups. RESULTS: At baseline, gestational age and corrected gestational age, birth weight, and gender were similar between both groups. Nutrient supply, length of total parenteral nutrition, and mechanical ventilation were also similar. BAP level increase in PG was 22.44 +/- 3.49 U/L, whereas in CG was 2.87 +/- 3.99 U/L (p = 0.003). There was a reduction of DPD levels in PG of 28.21 +/- 11.05 nmol/mmol, and an increase of 49.95 +/- 11.05 nmol/mmol (p < 0.001) in GC. CONCLUSION: The benefits of prevention and treatment of metabolic bone disease of prematurity, in addition to an adequate diet, should include these passive exercises with gentle joint compressions to improve the quality of premature infant's bones. PMID- 22773293 TI - Does delayed pushing in the second stage of labor impact perinatal outcomes? AB - OBJECTIVE: To estimate maternal, neonatal, and labor outcomes associated with delayed pushing. STUDY DESIGN: A retrospective cohort study of all consecutive women admitted to a single institution in labor at term who reached the second stage of labor. Pregnancies with multiple fetuses or major anomalies were excluded. Delayed pushing was defined as initiation of pushing >=60 minutes after complete dilatation. Primary outcome was mode of delivery. Multivariable logistic regression was used to control for confounding. RESULTS: Of the 5290 women who met inclusion criteria, 471 (8.9%) employed delayed pushing, and 4819 (91.1%) pushed immediately. Delayed pushing was associated with increased rates of cesarean, operative vaginal delivery, maternal fever, and lower arterial cord pH. Duration of the second stage and length of time spent pushing were significantly longer with delayed pushing. CONCLUSION: Delayed pushing is associated with lower rates of spontaneous vaginal delivery and increased adverse maternal and neonatal outcomes. PMID- 22773294 TI - Incidence and result of treatment-demanding retinopathy of prematurity using revised U.S. screening guidelines. AB - OBJECTIVE: To study the incidence of treated retinopathy of prematurity (ROP) using the revised U.S. screening guidelines, the rate of missed treatment, and unfavorable anatomic outcomes over a period of 2 years. STUDY DESIGN: We reviewed the admission records of premature patients treated at our hospital from September 2008 to August 2010. Any baby born with a gestational age (GA) of less than 30 weeks or a birth body weight (BW) of less than 2000 g was included in this study. The ROP screening followed the revised U.S. screening guidelines as presented in 2006. The indications of treatment for ROP were threshold disease as defined by the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity study and type 1 prethreshold ROP as defined by the Early Treatment for Retinopathy of Prematurity Randomized Trial study. RESULTS: There were 385 infants who were examined for ROP screening during this period. Nineteen babies (35 eyes) fit the treatment criteria and received treatment. The incidence of treatment-demand ROP was 4.9% (19/385). Four babies had a birth BW >1500 g (4/19; 21%). Seventeen babies received treatment during their first admission and two babies received treatment during outpatient follow-up. No baby missed timely treatment. Three eyes progressed to stage 4/5 after receiving intravitreal bevacizumab treatment. The success rate after primary bevacizumab was 91% (30/33 eyes). CONCLUSION: The incidence of treatment-demanding ROP using revised U.S. screening criteria was 4.9%. Teamwork and cooperation are very important to ensure that the highest-quality care possible is provided to patients in a timely manner. PMID- 22773292 TI - Cytokines and posthemorrhagic ventricular dilation in premature infants. AB - OBJECTIVE: To determine in extremely low-birth-weight infants if elevated blood interferon-gamma (IFN-gamma), interleukin (IL)-1beta, IL-18, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta are associated with need for shunt following severe intraventricular hemorrhage (IVH) or with ventricular dilation following milder grades/no IVH. STUDY DESIGN: Whole blood cytokines were measured on postnatal days 1, 3, 7, 14, and 21. Maximum IVH grade in the first 28 days, and shunt surgery or ventricular dilation on subsequent ultrasound (28 days' to 36 weeks' postmenstrual age) were determined. RESULTS: Of 902 infants in the National Institute of Child Health and Human Development Neonatal Research Network Cytokine study who survived to 36 weeks or discharge, 3.1% had shunts. Of the 12% of infants with severe (grade III to IV) IVH, 26% had a shunt associated with elevated TNF-alpha. None of the infants without IVH (69%) or with grade I (12%) or II (7%) IVH received shunts, but 8.4% developed ventricular dilation, associated with lower IFN-gamma and higher IL-18. CONCLUSION: Statistically significant but clinically nondiscriminatory alterations in blood cytokines were noted in infants with severe IVH who received shunts and in those without severe IVH who developed ventricular dilation. Blood cytokines are likely associated with brain injury but may not be clinically useful as biomarkers for white matter damage. PMID- 22773295 TI - The effect of troglitazone on lipid accumulation and related gene expression in Hanwoo muscle satellite cell. AB - The current study was undertaken to determine the effect of the troglitazone (TGZ) on the expression of peroxisome proliferator-activating receptor (PPARgamma), CCAAT/enhancer-binding protein, fatty acid binding protein 4, calpain 1 (CAPN1), and lipid accumulation in the myotube of Hanwoo muscle satellite cells. The satellite cells were treated with 5, 10, and 50 MUM of TGZ for indicated time intervals. TGZ promoted the trans-differentiation with significant increase in glycerol accumulation. Polymerase chain reaction (PCR) and microarray results indicated that the TGZ treatment significantly increased the expression of adipogenic transcription factors. TGZ (10 and 50 MUM) increased the CAPN1 gene expression 2.2- and 2.6-fold in real-time polymerase chain reaction analysis and 0.52- and 0.25-fold in microarray analysis, respectively, when compared with their respective controls. This result suggests that CAPN1 gene might be involved in the adipogenic differentiation programs. In addition, 13 genes were upregulated and 12 genes were downregulated in microarray analysis. Most of the up/downregulated genes were directly linked with adipogenesis. PMID- 22773296 TI - Dietary behaviors as associated factors for overweight and obesity in a sample of adolescents from Aquitaine, France. AB - This study aimed to identify dietary behaviors that might be considered as associated factors for overweight or obesity among French adolescents. Forty-nine of the 536 middle and high schools in Aquitaine (southwest of France) were invited to take part in the study. For each school, participating adolescents were selected using stratification by grade. A self-report questionnaire, including information about sex, age, dietary behaviors, physical and sedentary activities, and parental socioeconomic status (SES), was filled in by adolescents during class. Overweight and obesity were defined according to the age- and sex specific body mass index cutoff points of the International Obesity Task Force. Multivariate analysis (logistic regression) was used to identify independent dietary factors associated with overweight including obesity and obesity alone (adjustment on sex, age, parental SES, and weight status and adolescents' sedentary activity). In addition to parental SES and weight status and adolescents' sedentary activity, some dietary behaviors are also independently and significantly associated with a higher prevalence of overweight including obesity: absence (OR 1.43, 0.91-2.23) or rare (OR 1.57, 1.23-2.01) breakfast intake (p < 0.01) and absence (OR 5.03, 3.19-7.92) or rare (OR 1.90, 1.46-2.47) light afternoon meal intake (p < 0.001). All variables were also significantly and independently associated with obesity alone. This study shows that socioeconomic factors and individual behaviors are associated with overweight or obesity. These results confirm the importance to carry out multifaceted educational actions among adolescents, by promoting physical activity and healthy food choices in order to prevent overweight and promote healthy lifestyle behaviors. PMID- 22773297 TI - Lifestyle issues for colorectal cancer survivors--perceived needs, beliefs and opportunities. AB - PURPOSE: As survival rates for patients treated with colorectal cancer (CRC) increase, it is important to consider the short- and long-term self-management needs. The current work aimed to explore perceived patient needs for advice on diet, activity and beliefs about the role of lifestyle for reducing disease recurrence. METHODS: Forty colorectal cancer survivors, aged between 27 and 84, participated in six focus groups in community locations in the UK. RESULTS: The findings suggest that CRC survivors would welcome guidance on diet in the immediate posttreatment period to alleviate symptoms and fears about food choices. Many participants actively sought lifestyle advice but experienced confusion, mixed messages, culturally inappropriate guidance and uncertainty about evidence of benefit. There was scepticism over the role of diet and physical activity as causes of cancer, in part because people believed their lifestyles had been healthy and could not see how reinstating healthy behaviours would reduce future disease risk. The sense of changing lifestyle to 'stack the odds in their favour' (against recurrence) appeared a more meaningful concept than prevention per se. Those people who had made or maintained dietary changes highlighted the importance of these to contributing to wellbeing and a sense of control in their life. CONCLUSIONS: A dogmatic approach to lifestyle change may lead to perceptions of victim blaming and stigmatisation. Personalised, evidence informed, guidance on lifestyle choices does appear to be a much needed part of care planning and should be built in to survivorship programmes. PMID- 22773298 TI - Bone marrow necrosis in a girl with Hodgkin's disease. AB - Bone marrow necrosis (BMN) is a rare finding in children with malignancy occurring most commonly in children with acute lymphoblastic leukemia. This article describes the first case of a girl who developed BMN during treatment for Hodgkin's disease. During the second cycle of chemotherapy, she experienced sudden profound bone pain in the lumbosacral region associated with elevated levels of lactate dehydrogenase (LDH), fibrin degradation products (D-Dimer), and alkaline phosphatase as well as pancytopenia and leukoerythroblastosis. MRI studies showed multiple confluent areas with low signal intensity and rim contrast enhancement in all vertebral bodies. Bone marrow biopsy revealed focal necrosis within hypocellular bone marrow. The patient responded quickly to symptomatic treatment with analgetics and heparin; however, elevations of LDH and D-Dimer persisted for 1.5 and 8 months, respectively. Clinicians should be aware of this rare condition to establish the diagnosis and to continue oncologic treatment as early as possible. PMID- 22773299 TI - Outbreak of pandemic 2009 influenza A/H1N1 infection in the hematology ward: fatal clinical outcome of hematopoietic stem cell transplant recipients and emergence of the H275Y neuraminidase mutation. AB - We report an outbreak of pandemic 2009 influenza A/H1N1 virus (2009 H1N1) infection that occurred in the hematology ward of our institution during the 2010 2011 influenza season. A total of seven hospitalized patients with hematologic tumors, including five recipients of hematopoietic stem cell transplantation (HSCT), successively developed rapid influenza detection test (RIDT)-positive influenza A; four patients had laboratory-confirmed 2009 H1N1 infection. Three HSCT recipients required mechanical ventilation support and two were admitted to the intensive care unit; they died of progressive respiratory failure despite receiving available anti-viral drugs. We implemented outbreak-control measures including transferal of RIDT-positive patients to a single-patient room and chemoprophylaxis with oseltamivir. We note that the H275Y neuraminidase mutation was detected in respiratory specimens from three patients, who were administered therapeutic or prophylactic dosages of oseltamivir. The present report demonstrates that the nosocomial 2009 H1N1 outbreak in the hematology ward led to fatal clinical outcomes and the emergence of a resistant virus at a markedly high rate. PMID- 22773300 TI - Magnetism, f-electron localization and superconductivity in 122-type heavy fermion metals. AB - Both CeCu2Si2 and YbRh2Si2 crystallize in the tetragonal ThCr2Si2 crystal structure. Recent neutron-scattering results on normal-state CeCu2Si2 reveal a slowing down of the quasielastic response which complies with the scaling expected for a quantum critical point (QCP) of itinerant, i.e., three-dimensional spin-density-wave (SDW), type. This interpretation is in full agreement with the non-Fermi-liquid behavior observed in transport and thermodynamic measurements. The momentum dependence of the magnetic excitation spectrum reveals two branches of an overdamped dispersive mode whose coupling to the heavy charge carriers is strongly retarded. These overdamped spin fluctuations are considered to be the driving force for superconductivity in CeCu2Si2 (Tc = 600 mK). The weak antiferromagnet YbRh2Si2 (TN = 70 mK) exhibits a magnetic-field-induced QCP at BN = 0.06 T (B?c). There is no indication of superconductivity down to T = 10 mK. The magnetic QCP appears to concur with a breakdown of the Kondo effect. Doping induced variations of the average unit-cell volume result in a detachment of the magnetic and electronic instabilities. A comparison of the properties of these isostructural compounds suggests that 3D SDW QCPs are favorable for unconventional superconductivity. The question whether a Kondo-breakdown QCP may also give rise to superconductivity, however, remains to be clarified. PMID- 22773301 TI - Combined detection of mRNA expression of Alpha-fetoprotein in peripheral blood and telomerase activity of monocytes in hepatocellular carcinoma patients. AB - BACKGROUND/AIMS: The detection of hepatocellular carcinoma (HCC) cells in the peripheral blood is not only important for the diagnosis of FICC, but is also of critical importance for early detection of hematogenous metastasis of HCC. The purpose of this study was to measure Alpha-fetoprotein (AFP) mRNA in the peripheral blood and telomerase activity in peripheral blood monocytes to determine their utility, in isolation and concert, in the early diagnosis of HCC. METHODOLOGY: Nested RT-PCR was employed to detect the mRNA expression of AFP in the peripheral blood, and PCR-ELISA was used to measure the telomerase activity of peripheral blood mononuclear cells (PBMCs) in patients with HCC, benign hepatic tumors, chronic liver diseases and healthy subjects. RESULTS: Of the 30 HCC patients, 22 (73.3%) were positive for AFP, and 28/30 (93.3%) HCC patients were positive for telomerase activity. The mRNA expression of AFP was positively correlated with telomerase activity in HCC patients (r=0.6742, p<0.05). CONCLUSIONS: Detection of both mRNA expression of AFP in the peripheral blood and telomerase activity in PBMCs may prove to play an important role in achieving an early diagnosis of HCC. PMID- 22773302 TI - Influence of different anesthesia on liver and renal function in elderly patients undergoing laparoscopic colon or rectal resection. AB - BACKGROUND/AIMS: To investigate the influence of different anesthesia methods on liver and renal function in elderly patients undergoing laparoscopic colon or rectal resection. METHODOLOGY: Forty ASA I-II elderly patients undergoing elective laparoscopic colon or rectal resection were randomly divided into 2 groups (n=20 each): Group A: routine general anesthesia and Group B: general combined epidural anesthesia. All patients received general anesthesia, tracheal catheterized and mechanical ventilation. Data of liver and renal function were noted at these time points: before operation (T1), during operation (T2), 1-day after operation (T3), 2-day after operation during bowel anastomoses (T4), 3-day after operation (T5). Duration of surgery, blood loss, urine output and intravenous fluid volume was registered. RESULTS: Compared with group A, the total fluid volume and urine volume were increased in group B (p<0.05), while the amount of fentanyl was decreased (p<0.05). TP, TBIL and DBIL between the two groups were not significantly different (p>0.05). Compared with group A, group B ALT/BUN decreased at T2 and T3, AST decreased at T2, Cr at T3 decreased, ALB decreased at T2 (p<0.05). CONCLUSIONS: Continuous epidural block compound general anesthesia in elderly laparoscopic colorectal resection surgery is more conducive to the protection of perioperative liver and kidney function. PMID- 22773303 TI - Comparison of duct-to-mucosa and end-to-side pancreaticojejunostomy reconstruction following pancreaticoduodenectomy. AB - BACKGROUND/AIMS: Pancreaticojejunostomy reconstruction following pancreaticoduodenectomy still remains a debate because of high incidence of complications. To compare the effect of duct-to-mucosa and end-to-side pancreaticojejunostomy reconstruction following pancreaticoduodenectomy, we retrospectively reviewed two groups of patients who underwent duct-to-mucosa or end-to-side pancreaticojejunostomy reconstruction. METHODOLOGY: Over a period of 6 years, 240 consecutive patients underwent duct-to-mucosa (group A) or end-to side (group B) pancreaticojejunostomy reconstruction following pancreaticoduodenectomy. RESULTS: There were no statistical differences between group A and B in regards to age, gender, preoperative serum levels of total bilirubin, alanine aminotransferase, albumin, pathological features, amount of intraoperative bleeding and duration of operation. The overall incidence of postoperative complications was 26.7 % (22.2% in group A, 30.3% in group B, p>0.05). Of 108 patients in group A, pancreatic fistula occurred in 10 (9.3%) patients and of 132 patients in group B, pancreatic fistula occurred in 14 (10.6%) patients (p>0.05). The overall hospital mortality was 4.2% (3.7% in group A, n=4; 4.5% in group B, n=6, p>0.05). The postoperative hospital stay (mean +/ SD) for group A was 20.3+/-19.7 days, for group B was 23.3+14.3 days (p>0.05). CONCLUSIONS: Our results showed no statistical difference between the two techniques in decreasing postoperative complications including pancreatic fistula or postoperative hospital stay. PMID- 22773304 TI - Duodenum-preserving pancreatic head resection vs. pancreatoduodenectomy for benign lesions and low-grade malignancies of the pancreatic head. AB - BACKGROUND/AIMS: To compare the postoperative results of duodenum-preserving pancreatic head resection (DPPHR) techniques with those of conventional pancreatoduodenectomy (PD). METHODOLOGY: We retrospectively reviewed the records of 58 patients who underwent DPPHR or PD at Jinhua central hospital between May 1998 and May 2011. RESULTS: Eighteen patients underwent DPPHR (Group 1) and 40 conventional PD (Group 2). They were followed up for more than 6 months. Operation time in Group 1 was longer (290+/-18 min vs 269+/-14 min, p=0.001). Estimated blood loss in Group 1 was more (633+/-88 mL vs. 495+/-131 mL, p=0.003). Intraoperative transfusion in Group 1 was more (533+/-88 mL vs. 335+/-218 mL, p=0,001). However, postoperative transfusion was Iess (141+/-162 mL vs. 440+/-193 mL, p=0.000). Group 1 had a lower short-term complication rate (16.67% vs. 50.0%, p=0.0 16) and long-term complication rate (11.11% vs. 45.0%, p=0.012). Hospital mortality of both groups were 0. CONCLUSIONS: DPPHR for benign or premalignant lesions is a difficult procedure, but with a lower complication rate than conventional PD. Preserving the entire duodenum and a normal biliary tree allows better short-term and long-term results. DPPHR will be suitable for only a small group of patients and should be performed by experienced surgeons. PMID- 22773305 TI - Ulysses arrangements in psychiatric treatment: towards proposals for their use based on 'sharing' legal capacity. AB - A 'Ulysses arrangement' (UA) is an agreement where a patient may arrange for psychiatric treatment or non-treatment to occur at a later stage when she expects to change her mind. In this article, I focus on 'competence-insensitive' UAs, which raise the question of the permissibility of overriding the patient's subsequent decisionally competent change of mind on the authority of the patient's own prior agreement. In "The Ethical Justification for Ulysses Arrangements", I consider sceptical and supportive arguments concerning competence-insensitive UAs, and argue that there are compelling reasons to give such UAs serious consideration. In "Decisional Competence and Legal Capacity in UAs", I examine the nature of decisional competence and legal capacity as they arise in UAs, an issue neglected by previous research. Using the distinctions which emerge, I then identify the legal structure of a competence-insensitive UA in terms of the types of legal capacity it embodies and go on to explain how types of legal capacity might be shared between the patient and a trusted other to offer support to the patient in the creation and implementation of a competence-insensitive UA. This is significant because it suggests possibilities for building patient support mechanisms into models of legal UAs, which has not addressed in the literature to date. Drawing on this, in "Using Insights from the Competence/Capacity Distinction to Enhance Patient Support in UAs", I offer two possible models to operationalize competence-insensitive UAs in law that allow for varying degrees of patient support through the involvement of a trusted other. Finally, I outline some potential obstacles implementing these models would face and highlight areas for further research. PMID- 22773306 TI - Akap200 suppresses the effects of Dv-cbl expression in the Drosophila eye. AB - The Drosophila melanogaster orthologue of the c-Cbl proto-oncogene acts to downregulate signalling from receptor tyrosine kinases by enhancing endocytosis of activated receptors. Expression of an analogue of the C-terminally truncated v Cbl oncogene, Dv-cbl, in the developing Drosophila eye conversely leads to excess signalling and disruption to the well-ordered adult compound eye. Co-expression of activated Ras with Dv-cbl leads to a severe disruption of eye development. We have used a transposon-based inducible expression system to screen for molecules that can suppress the Dv-cbl phenotype and have identified an allele that upregulates the A-kinase anchoring protein, Akap200. Overexpression of Akap200 not only suppresses the phenotype caused by Dv-cbl expression, but also the severe disruption to eye development caused by the combined expression of Dv-cbl and activated Ras. Akap200 is also endogenously expressed in the developing Drosophila eye at a level that modulates the effects of excessive signalling caused by expression of Dv-cbl. PMID- 22773307 TI - Analysis of the transcriptome of differentiating and non-differentiating preadipocytes from rats and humans by next generation sequencing. AB - Alongside cell lines such as 3T3-L1 cells, primary cell culture models of adipogenesis have helped in developing an understanding of the process of adipocyte recruitment and maintenance, which may lead to therapeutic advances to treat the growing epidemic of obesity. Recently, it has been demonstrated that fat cell progenitors (DFAT) established through ceiling culture of adipocytes retain an enhanced ability to undergo adipocyte differentiation compared to preadipocytes isolated from the stromal vascular fraction of adipose tissue. Clonal expansion of rat DFAT cells identified differentiation capable and incapable cell strains. To understand the mechanisms underlying these differences, comparison of their transcriptomes by next generation sequencing was performed. Two hundred seventy-eight genes with a significant fold change of 1.4 were detected as being consistently deregulated between differentiating and non differentiating strains. Bioinformatic network analyses identified components of the extra-cellular matrix and PPARgamma as important genes in this process, suggesting crosstalk between ECM and transcription factors influences differentiation. Analyses of the transcriptomes of human DFAT cells in early and late passage (non-differentiating) confirmed the importance of these pathways in maintaining an adipogenic potential. PMID- 22773308 TI - Assessing spatial variation and overall density of aerially broadcast toxic bait during a rat eradication on Palmyra Atoll. AB - Baits containing brodifacoum rodenticide were aerially applied to eradicate invasive black rats from Palmyra Atoll, an important biodiversity center. Bait application must be sufficient to be effective, while minimizing environmental hazards by not exceeding designated label rates, prompting our bait density assessments for two aerial drops. With few physical or human resources on this remote, uninhabited atoll, assessments were particularly challenging, requiring observations within 30 min of aerial application to avoid bait loss to rats, crabs, or elements. We estimated bait density using quadrat sampling within 13 terrestrial sampling areas. We also sampled 10 tidal flat areas to assess inadvertent bait scatter into marine aquatic environments. Of particular value for challenging sampling circumstances, our quadrats had to be lightweight and durable, which we addressed by using widely available PVC hoops ("Hula Hoops"), the size of which was ideal for sampling purposes. At 77.5 and 78.7 kg/ha, overall bait densities were very near to the target densities of 80 and 75 kg/ha, respectively. However, considerable variability in bait densities existed among sampled areas, 8.6-178.2 and 31.4-129.5 kg/ha for the respective drops, respectively. Environmental, human, and equipment factors likely accounted for this variability. Tidal flat sampling revealed variable bait scatter into aquatic environments, from 0-46.3 kg/ha across the two drops. No differences were found in average bait densities among 1-, 4-, and 7-m distances from high tide lines. Our methods might broadly assist bait density (and other) surveys under challenging circumstances. PMID- 22773309 TI - Hollow ruthenium nanoparticles with small dimensions derived from Ni@Ru core@shell structure: synthesis and enhanced catalytic dehydrogenation of ammonia borane. AB - Hollow Ru nanoparticles with ~14 nm diameter and ~2 nm shell thickness are reported for the first time, by removal of Ni from the delicately designed Ni@Ru core@shell NPs. Such hollow Ru NPs exhibit enhanced catalytic activity in the dehydrogenation of ammonia borane with respect to solid ones. PMID- 22773312 TI - High energy pseudogap and its evolution with doping in Fe-based superconductors as revealed by optical spectroscopy. AB - We report optical spectroscopic measurements on electron- and hole-doped BaFe2As2. We show that the compounds in the normal state are not simple metals. The optical conductivity spectra contain, in addition to the free carrier response at low frequency, a temperature-dependent gap-like suppression at fairly high energy scale near 0.6 eV. This suppression evolves with the As-Fe-As bond angle induced by electron or hole doping. Furthermore, the feature becomes much weaker in the Fe-chalcogenide compounds. We elaborate that the feature is mainly caused by the strong Hund's rule coupling effect between the itinerant electrons and localized electron moment arising from the multiple Fe 3d orbitals. The coupling strength changes with the environment of the Fe atom. Our experiments demonstrate the coexistence of itinerant and localized electrons in iron-based compounds, which would then lead to a more comprehensive picture of the metallic magnetism in the materials. PMID- 22773311 TI - Ethyl glucuronide concentrations in beard hair after a single alcohol dose: evidence for incorporation in hair root. AB - BACKGROUND: Despite the growing importance of ethyl glucuronide (EtG) in hair for detection of chronic excessive alcohol consumption, the mechanism of incorporation is not yet clear. Deposition from sweat is believed to be the main route. In order to get more information, EtG was determined in daily shaved beard hair after single higher alcohol doses. METHODS: Three volunteers drank within 5.5 h 153, 165 and 200 g ethanol followed by abstinence. Daily shaved beard hair was analysed for EtG using a validated liquid chromatography-tandem mass spectrometry method with a limit of quantification of 2 pg/mg. RESULTS: For all three volunteers, small concentrations of EtG were already detected 9 h after end of drinking. The concentrations increased to maxima of 182, 242 and 74 pg/mg on days 2 to 4 and then gradually decreased to limit of quantification on days 8 to 10. DISCUSSION: The time course of EtG is discussed based on literature data about anatomic dimensions of the hair root, physiology of hair growth, kinetics of EtG formation and elimination in blood, and in comparison to literature results about drugs in beard hair. It follows that for beard hair the predominant portion of EtG is incorporated in the upper part of the hair root between suprabulbar region and isthmus leading to a positive zone of about 3 mm (8-9 days) after a single drinking event. Deposition from sweat which is only possible into the residual hair stubble after shaving and in the infundibulum down to the sebaceous gland mouth was found to be of minor importance but could play a greater role in long hair. CONCLUSION: It is concluded that EtG in hair fulfils the prerequisites for time-resolved interpretation of segmental concentrations and that a single excessive drinking can be well detected in sufficiently short hair segments. However, in the routinely investigated 3-cm proximal scalp hair segment and using the cutoff of 7 pg/mg, a negative result can be expected with high probability because of dilution by negative hair. PMID- 22773310 TI - Targeting cyclooxygenase-2 in depression is not a viable therapeutic approach and may even aggravate the pathophysiology underpinning depression. AB - Depression is a complex progressive disorder accompanied by activation of inflammatory and Th-1 driven pathways, oxidative and nitrosative stress (O&NS), lowered antioxidant levels, mitochondrial dysfunctions, neuroprogression and increased bacterial translocation. In depression, activation of immuno inflammatory pathways is associated with an increased risk for cardio-vascular disorder (CVD). Because of the inflammatory component, the use of cyclooxygenase 2 (COX-2) inhibitors, such as celecoxib, has been advocated to treat depression. Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as sources for this selective review on the effects of COX-2 inhibitors aggravating the abovementioned pathways. COX-2 inhibitors may induce neuroinflammation, exacerbate Th1 driven responses, increase lipid peroxidation, decrease the levels of key antioxidants, damage mitochondria and aggravate neuroprogression. COX-2 inhibitors may aggravate bacterial translocation and CVD through Th1-driven mechanisms. COX-2 inhibitors may aggravate the pathophysiology of depression. Since Th1 and O&NS pathways are risk factors for CVD, the use of COX-2 inhibitors may further aggravate the increased risk for CVD in depression. Selectively targeting COX-2 may not be a viable therapeutic approach to treat depression. Multi-targeting of the different pathways that play a role in depression is more likely to yield good treatment results. PMID- 22773313 TI - Some applications of pharmacogenomics and epigenetics in drug development and use in pursuit of personalized medicine. AB - Personalized medicine has become the most recent mantra of the pharmaceutical industry. While truly affordable bespoke drugs may never be totally achievable, pharmacogenomics and epigenetics will play significant roles in developing targeted therapy tailored to subpopulations of disease sufferers most likely to benefit. Personalized medicine is a very attractive concept, but an extremely difficult reality to achieve due to theoretical and practical considerations. Foremost among the theoretical reasons is our dearth of knowledge of individual physiology and metabolism, as well as the interactions of genetics and environment in the development of most diseases. Amongst the practical reasons, there is the cost of new drug development, considered to be about 800 million to one billion dollars (J Health Econ 22:151-185, DiMasi et al. 2003; Health Econ 19:130-141, Adams and Vu Brantner 2010) and the fact that many drugs now on the market do display reasonable efficacy in large segments of the population with acceptable side effects. Thus, the market for "personalized" drugs may not be large enough to support the costs of development. Another factor is the limitations put on healthcare by governments and insurance companies which promote the use of generics rather than the creation of new chemical entities. Finally, there are the social and ethical considerations of turning individual biology into noughts and ones with the possibility of such information becoming public and/or being used to constrain the way one lives or the care one receives (Nat Rev Drug Discov 1:300-308, Issa 2002). That said, to the degree that personalized medicine does become possible, pharmacogenomics and epigenetics will play significant roles in drug development and use. PMID- 22773314 TI - All-inside meniscal repair using the FasT-Fix meniscal repair system: is still needed to avoid weight bearing? A systematic review. AB - The aim of this study was to review the published clinical outcomes of meniscal repair using the FasT-Fix device comparing standard rehabilitation program to an accelerated rehabilitation protocol. A review of the Medline database was performed involving searches for clinical outcomes of all-inside meniscus repair performed with the FasT-Fix device. Eight studies were identified for inclusion. On the basis of the clinical outcomes of these studies, there appears to be no notable difference between an accelerated rehabilitation regimen with full weight bearing allowed as soon as tolerated and a standard postoperative rehabilitation program. Failure rate was 13 % for patients following an accelerated rehabilitation regimen, and 10 % for standard protocol. Accelerated rehabilitation after all-inside meniscal repair using the FasT-Fix device appears to be safe, and the incidence of retears is in line with those reported for standard rehabilitation protocol. PMID- 22773318 TI - Physical activity/fitness peaks during perimenopause and BMI change patterns are not associated with baseline activity/fitness in women: a longitudinal study with a median 7-year follow-up. AB - OBJECTIVE: To assess the age-associated longitudinal trends in cardiorespiratory fitness (CRF), leisure-time physical activity (PA), and body mass index (BMI) across the lifespan in a cohort of adult women. METHODS: The sample included 1467 women from the Aerobics Center Longitudinal Study who were 30-79 years old at baseline and had 3-22 health examinations between 1971 and 2006. CRF was quantified by maximal Balke treadmill exercise tests. The total metabolic equivalent-minutes/week of self-reported PA and measured BMI (kg/m(2)) were calculated. RESULTS: The overall pattern of CRF decreased over time. After age 60 years, fitness level tended to decline rapidly. Women at age 50 had the highest PA level, which decreased after age 50 and plateaued at age 60. The overall pattern of BMI increased with age. However, after age 60 years the rate of increase in BMI became much slower. Adjusting for smoking, health status, and the individual exposures of CRF, PA and BMI did not influence the observed associations. Women who did not meet current PA recommendation or those who were low fit at baseline had a higher BMI throughout adulthood than their more active or fit peers, but the trajectory of BMI was unassociated with baseline activity or fitness levels. CONCLUSION: We concluded that the age-related longitudinal patterns in physical activity and fitness are not linear. Baseline activity and fitness levels are associated with BMI status during adulthood, but do not affect BMI change trajectory. PMID- 22773320 TI - Limitations of serum values to estimate glomerular filtration rate during exercise. AB - OBJECTIVE: Glomerular filtration rate (GFR) is part of routine medical practice for clinical assessment of kidney function in health and disease conditions, and is determined by measuring the clearance of creatinine (Cl-Crn) or estimated (eGFR) from equations using serum creatinine (Crn) or cystatin C (Cyst C). Crn and Cyst C methods obviate the need for urine collection but their reliability under non-resting conditions is uncertain. This study compared GFR determined by Cl-Crn, Crn and Cyst C methods under the conditions of rest and after exercise. METHODS: Twelve young male subjects performed a 30 min treadmill exercise at 80% of the maximal oxygen capacity. Venous blood samples and urine collections were collected before and after exercise and after recovery period. GFR rates were calculated from serum Crn and Cyst C equations, and Cl-Crn measured from serum and urine Crn output. Albumin was also determined for all samples. RESULTS: Under resting conditions, eGFR from Crn and Cyst C did not differ from Cl-Crn (p=0.39). Immediately after exercise, GFR decreased significantly, regardless of the method, but more so for Cl-Crn (-30.0%; p<0.05) compared with Crn (-18.2%) and Cyst C (-19.8%). After the recovery period, GFR determined by Cl-Crn was returned to initial values whereas Crn and Cyst C remained reduced. Although eGFR methods accurately estimate GFR at rest, those methods underestimated the change in GFR after acute exercise. CONCLUSIONS: These results indicate that exercise-induced changes in GFR should be determined by Cl-Crn method. PMID- 22773321 TI - Diagnostic accuracy of clinical tests of the hip: a systematic review with meta analysis. AB - BACKGROUND: Hip Physical Examination (HPE) tests have long been used to diagnose a myriad of intra-and extra-articular pathologies of the hip joint. Useful clinical utility is necessary to support diagnostic imaging and subsequent surgical decision making. OBJECTIVE: Summarise and evaluate the current research and utility on the diagnostic accuracy of HPE tests for the hip joint germane to sports related injuries and pathology. METHODS: A computer-assisted literature search of MEDLINE, CINHAL and EMBASE databases (January 1966 to January 2012) using keywords related to diagnostic accuracy of the hip joint. This systematic review with meta-analysis utilised the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the search and reporting phases of the study. Der-Simonian and Laird random effects models were used to summarise sensitivities (SN), specificities (SP), likelihood ratios and diagnostic OR. RESULTS: The employed search strategy revealed 25 potential articles, with 10 demonstrating high quality. Fourteen articles qualified for meta-analysis. The meta-analysis demonstrated that most tests possess weak diagnostic properties with the exception of the patellar-pubic percussion test, which had excellent pooled SN 95 (95% CI 92 to 97%) and good specificity 86 (95% CI 78 to 92%). CONCLUSION: Several studies have investigated pathology in the hip. Few of the current studies are of substantial quality to dictate clinical decision-making. Currently, only the patellar-pubic percussion test is supported by the data as a stand-alone HPE test. Further studies involving high quality designs are needed to fully assess the value of HPE tests for patients with intra- and extra articular hip dysfunction. PMID- 22773322 TI - Which physical examination tests provide clinicians with the most value when examining the shoulder? Update of a systematic review with meta-analysis of individual tests. AB - OBJECTIVE: To update our previously published systematic review and meta-analysis by subjecting the literature on shoulder physical examination (ShPE) to careful analysis in order to determine each tests clinical utility. METHODS: This review is an update of previous work, therefore the terms in the Medline and CINAHL search strategies remained the same with the exception that the search was confined to the dates November, 2006 through to February, 2012. The previous study dates were 1966 - October, 2006. Further, the original search was expanded, without date restrictions, to include two new databases: EMBASE and the Cochrane Library. The Quality Assessment of Diagnostic Accuracy Studies, version 2 (QUADAS 2) tool was used to critique the quality of each new paper. Where appropriate, data from the prior review and this review were combined to perform meta-analysis using the updated hierarchical summary receiver operating characteristic and bivariate models. RESULTS: Since the publication of the 2008 review, 32 additional studies were identified and critiqued. For subacromial impingement, the meta-analysis revealed that the pooled sensitivity and specificity for the Neer test was 72% and 60%, respectively, for the Hawkins-Kennedy test was 79% and 59%, respectively, and for the painful arc was 53% and 76%, respectively. Also from the meta-analysis, regarding superior labral anterior to posterior (SLAP) tears, the test with the best sensitivity (52%) was the relocation test; the test with the best specificity (95%) was Yergason's test; and the test with the best positive likelihood ratio (2.81) was the compression-rotation test. Regarding new (to this series of reviews) ShPE tests, where meta-analysis was not possible because of lack of sufficient studies or heterogeneity between studies, there are some individual tests that warrant further investigation. A highly specific test (specificity >80%, LR+ >= 5.0) from a low bias study is the passive distraction test for a SLAP lesion. This test may rule in a SLAP lesion when positive. A sensitive test (sensitivity >80%, LR- <= 0.20) of note is the shoulder shrug sign, for stiffness-related disorders (osteoarthritis and adhesive capsulitis) as well as rotator cuff tendinopathy. There are six additional tests with higher sensitivities, specificities, or both but caution is urged since all of these tests have been studied only once and more than one ShPE test (ie, active compression, biceps load II) has been introduced with great diagnostic statistics only to have further research fail to replicate the results of the original authors. The belly-off and modified belly press tests for subscapularis tendinopathy, bony apprehension test for bony instability, olecranon-manubrium percussion test for bony abnormality, passive compression for a SLAP lesion, and the lateral Jobe test for rotator cuff tear give reason for optimism since they demonstrated both high sensitivities and specificities reported in low bias studies. Finally, one additional test was studied in two separate papers. The dynamic labral shear may be sensitive for SLAP lesions but, when modified, be diagnostic of labral tears generally. CONCLUSION: Based on data from the original 2008 review and this update, the use of any single ShPE test to make a pathognomonic diagnosis cannot be unequivocally recommended. There exist some promising tests but their properties must be confirmed in more than one study. Combinations of ShPE tests provide better accuracy, but marginally so. These findings seem to provide support for stressing a comprehensive clinical examination including history and physical examination. However, there is a great need for large, prospective, well-designed studies that examine the diagnostic accuracy of the many aspects of the clinical examination and what combinations of these aspects are useful in differentially diagnosing pathologies of the shoulder. PMID- 22773323 TI - Is the repeatable battery for the assessment of neuropsychological status factor structure appropriate for inpatient psychiatry? An exploratory and higher-order analysis. AB - The present study, utilizing a sample of inpatients with schizophrenia or schizoaffective disorder (n = 167), examined the factor structure of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Principal axis exploratory factor analysis, multiple factor extraction criteria, and higher-order factor analysis were used. Results were inconsistent with the five-factor structure of the RBANS purported in the test manual. Factor extraction criteria recommended extraction of one or two factors. Extraction of two factors resulted in a memory dimension and a less homogeneous visual perception and processing speed dimension. Higher-order analysis found that a second-order factor, representing general neurocognitive functioning, accounted for over three times the total and common variance than the two first-order factors combined. It was concluded that although the RBANS appears to be a useful measure of general neurocognitive functioning for inpatients with schizophrenia or schizoaffective disorder, clinical interpretation beyond a general factor (i.e., Total Scale score) should be done with caution in this population. Limitations of the present study and directions for future research are discussed. PMID- 22773324 TI - Rectal douching among Peruvian men who have sex with men, and acceptability of a douche-formulated rectal microbicide to prevent HIV infection. PMID- 22773325 TI - Epidemiological treatment for chlamydia co-infection in men who have sex with men (MSM) with a presumptive diagnosis of urethral gonorrhoea in South Australia. PMID- 22773326 TI - Repeat chlamydia screening among adolescents: cohort study in a school-based programme in New Orleans. AB - OBJECTIVES: To describe uptake of chlamydia screening, determine rates of repeated yearly screening and investigate determinants of repeated participation in an organised school-based screening programme. METHODS: The authors analysed data from 1995 to 2005 from female and male students in up to 13 schools in New Orleans, Louisiana, USA. The authors calculated proportions of students tested among all enrolled students and among those with parental consent and the percentage of positive chlamydia tests in each school year. The authors used random effects logistic regression to examine the effect of past screening history on subsequent participation. RESULTS: 35 041 students were registered for at least one school year. Overall coverage was >30% in all school years. Among all students registered for 4 years, 10.6% (95% CI 9.3% to 12.0%) of women and 12.7% (95% CI 11.2% to 14.2%) of men had a test every year. Among students with parental consent for 4 years, 49.3% (95% CI 44.6% to 54.1%) of women and 59.3% (95% CI 54.5% to 64.0%) of men had a test every year. Among students registered for 2 or more years, those with a previous positive chlamydia test were less likely to have a subsequent test (female adjusted OR 0.77, 95% CI 0.67 to 0.88 and male adjusted OR 0.84, 95% CI 0.69 to 1.02). Chlamydia positivity increased over time. CONCLUSIONS: High levels of uptake can be achieved in school-based chlamydia screening programmes, but repeated yearly screening is difficult to sustain over time. PMID- 22773327 TI - The prevalence of HIV and hepatitis C in individuals leaving prison and entering drug and alcohol treatment services. PMID- 22773328 TI - The importance of low-risk HPV infection for the risk of abnormal cervical cytology/histology in more than 40 000 Danish women. AB - OBJECTIVES: To estimate the age and type-specific distribution of low-risk (LR) human papillomavirus (HPV) types in cervical samples from women in the general population and to assess the distribution of LR-HPV without the coexistence of high-risk HPV types in different cytology and histology categories. METHODS: In a cross-sectional study, liquid-based cytology samples (SurePath) were collected over a 3-year period. The samples were HPV tested by Hybrid Capture II (HC2; Digene) and genotyped using a PCR-based assay (INNO-LiPAv2; Innogenetics Inc.). A total of 40 382 women (14-95 years of age) were included in the study. By linkage with the nationwide Pathology Data Bank, the HPV test results were directly linked to cytological diagnoses made from the same samples and to subsequent histology results. RESULTS: Overall, 2790 women (6.9%) tested positive for LR-HPV types, with HPV6 and HPV70 being the most frequent types detected, whereas HPV11 was uncommon. The highest prevalence was observed in the youngest age group (<=19 years). The LR-HPV prevalence was 6.3% in women with normal cytology, 33.1% in atypical squamous cells of undetermined significance (ASCUS), 19.6% in low-grade squamous intraepithelial lesion and 12.7% in those with high-grade squamous intraepithelial lesion. When considering women with LR-HPV alone, the prevalence was 2.0% (normal cytology), 11.3% (ASCUS), 2.6% (low-grade squamous intraepithelial lesion) and 0.7% in women with high-grade squamous intraepithelial lesion, respectively. A similar pattern was observed in relation to the histological diagnoses with the majority of LR-HPV infections detected in CIN1 lesions (24.7%). CONCLUSIONS: LR-HPV types alone are relatively common in ASCUS, whereas LR-HPV types without coexisting high-risk HPV types are virtually never detected in severe cervical lesions. PMID- 22773329 TI - Exploring staff attitudes to routine HIV testing in non-traditional settings: a qualitative study in four healthcare facilities. AB - OBJECTIVES: To explore staff attitudes towards and experiences of the implementation of routine HIV testing in four healthcare settings in areas of high diagnosed HIV prevalence. METHODS: As part of the HINTS (HIV Testing in Non traditional Settings) Study, routine offer of an HIV test to all 16-65-year-old patients was conducted for 3 months in an emergency department, an acute admissions unit, a dermatology outpatients department and a primary care practice. The authors conducted focus groups with staff at these sites before and after the implementation of testing. Transcriptions of focus groups were subject to thematic analysis. RESULTS: Four major themes were identified: the stigma of HIV and exceptionalisation of HIV testing as a condition; the use of routine testing compared with a targeted strategy as a means of improving the acceptability of testing; the need for an additional skill set to conduct HIV testing; and the existence within these particular settings of operational barriers to the implementation of HIV testing. Specifically, the time taken to conduct testing and management of results were seen by staff as barriers. There was a clear change in staff perception before and after implementation of testing as staff became aware of the high level of patient acceptability. CONCLUSIONS: The routine offer of HIV testing in general medical services is feasible, but implementation requires training and support for staff, which may be best provided by the local sexual health service. PMID- 22773330 TI - Can Chlamydia screening in the Emergency Department reach a different section of the target population? PMID- 22773331 TI - Deadly public policy: what the future could hold for the HIV epidemic among injection drug users in Vancouver. AB - The scope and scale of the HIV outbreak that occurred among injection drug users in Vancouver in the late 1990s was unprecedented and resulted in some 2,000 new HIV infections, with incidence rates reaching 18 per 100 person-years. This outbreak, localized mainly in one neighbourhood, cost the Canadian health care system more than 1 billion dollars to diagnose, care and treat. A number of factors combined to stabilize HIV incidence: 1) HIV prevalence became saturated among those at highest risk; 2) several public health policies focused on drug users were implemented, including increased and additional decentralized needle exchange programs, expanded methadone maintenance services, better addiction treatment services, improved housing, and mental health programs; and 3) increased access and expansion of Highly Active Antiretroviral Therapy. To ensure that a similar outbreak never occurs again in Vancouver and other cities, future health policy must consider the political, psychosocial and socioeconomic factors that contributed to this outbreak. These policies must address the unintended adverse consequences of past policies and their repercussions for marginalized individuals living in this community and beyond. PMID- 22773332 TI - Cadmium effects on the fitness-related traits and antioxidative defense of Lymantria dispar L. larvae. AB - Cadmium, like many other pollutants, is nondegradable and can be accumulated by Lymantria dispar at a level that affects fitness components, physiology, and development, which could indicate presence of environment pollution by heavy metals. The cadmium effect on fitness-related traits in the third, fourth, fifth, and sixth instar of L. dispar L. was determined. Furthermore, activities of the following antioxidative defense components after the larvae had been fed on the artificial cadmium-supplemented diet (50 MUg Cd/g dry food) were assessed: superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APOX), total glutathione amount (GSH), glutathione-S-transferase (GST), glutathione reductase (GR), and the amount of free sulfhydryl (SH) groups. Statistically significant delay of development in the fourth, fifth, and sixth instar and decrease of the larval mass in the third and fourth instar were estimated after the exposure to cadmium through food in comparison to the control. There were no changes in SOD activity of cadmium-treated larvae. Significantly lower CAT, APOX, and GR activities were recorded in the third, fifth, and in the third instar, respectively. At the same time, higher activity was recorded in the sixth instar, while GST activity was higher in the third. GSH content was significantly lower during all instars after treatment but the amount of SH groups was higher in older larvae. The strategy of antioxidative defense and the adjustment or modulation of fitness-related traits in presence of cadmium was dependent on the age of larvae in L. dispar, which might be used in early metal risk assessment in Lepidoptera and other insects. PMID- 22773333 TI - Cd accumulation and phytostabilization potential of dominant plants surrounding mining tailings. AB - The objectives of the present study were to compare nine dominant plant species growing in mine tailings and nonmining areas in terms of biomass and Cd concentrations and to search for Cd accumulation and tolerance. Also, more detailed experiments were conducted on Athyrium wardii using a pot experiment to assure its Cd-accumulation ability and tolerance as a potential phytostabilizer of Cd-polluted soils. Nine dominant plant species growing on Pb/Zn mine tailings and their corresponding nonmining ecotypes were investigated for their potential to phytostabilize Cd. The performance of A. wardii exposed to high levels of Cd was investigated under controlled conditions. A field study revealed that the Cd concentrations in the roots of these plants ranged from 0.21 to 251.07 mg kg(-1), and the highest concentrations were found in A. wardii, which reached a concentration of 69.78, 251.07, and 126.35 mg kg(-1) during the early growth stage (May), vigorous growth stage (August), and late growth stage (October), respectively. The Cd concentrations of roots among the nine mining ecotypes were positively correlated with available content of Cd in the rhizosphere soils, whereas a negative correlation was observed in the nonmining ecotypes. A pot experiment showed that the mining ecotype of A. wardii had a higher biomass production and Cd retention capacity in roots than that of the nonmining ecotype. Due to the relatively high tolerance to Cd and the capacity of roots to retain this metal, A. wardii may be useful for the phytostabilization of soils contaminated by Cd. PMID- 22773334 TI - Enhanced staff communication and reduced near-miss errors with a neurointerventional procedural checklist. AB - INTRODUCTION: Over the past several decades, checklists have emerged in a variety of different patient care settings to help reduce medical errors and ensure patient safety. To date, there have been no published accounts demonstrating the effectiveness of checklists designed specifically for the unique demands of neurointerventional procedures. METHODS: A three-part, 20-item checklist was developed specific to neurointerventional procedures using the WHO surgical checklist as a template. Staff members (nurses, radiation technologists and physicians) were surveyed regarding near-miss adverse events and the quality of communication immediately following each neurointerventional procedure for 4 weeks prior to implementation of the checklist and again for 4 weeks after using the checklist. Staff members were asked to complete final surveys at the end of the study period. RESULTS: 71 procedures were performed during the 4 weeks prior to checklist implementation and 60 procedures were performed during the 4 weeks after institution of the checklist. Post-checklist surveys indicated significantly improved communication compared with pre-checklist surveys (chi(2) 29.4, p<0.001). The number of adverse events was lower after checklist implementation for eight of the nine adverse event types (not individually significant), but the total number of adverse events was significantly lower after checklist implementation (chi(2) 11.4, p=0.001). Final staff surveys were uniformly positive with 95% of individuals indicating that the checklist should be continued in the department. CONCLUSIONS: Use of a neurointerventional procedural checklist resulted in statistically significant improvements in team communication and a significant reduction in total adverse events, with uniformly positive staff feedback. PMID- 22773335 TI - Analysis of utilization patterns of vertebroplasty and kyphoplasty in the Medicare population. AB - OBJECTIVE: To determine the pattern of utilization of vertebral augmentation procedures including vertebroplasty and kyphoplasty of the lumbar and thoracic spine in the Medicare population in the USA. METHODS: This analysis was performed using a standard 5% national sample of the Centers for Medicare and Medicaid Services physician outpatient billing claims from 2001 to 2008 and the Physician/Supplier Procedure Summary Master File for 2009 and 2010. Overall characteristics of utilization patterns for vertebral augmentation procedures were evaluated using multiple variables. RESULTS: From 2002 to 2010, vertebroplasty procedures decreased overall by 24.6% with an average annual decrease of 3.5% per 100 000 Medicare population; from 2006 to 2010 the declines were 42.4% overall and 12.9% annually. From 2006 to 2010, kyphoplasty procedures increased overall by 0.8% with an annual average increase of 0.2% per 100 000 Medicare population. CONCLUSION: Analysis of growth patterns of vertebroplasty and kyphoplasty in the Medicare population from 2002 to 2010 illustrates a lack of growth of kyphoplasty and a decline in vertebroplasty procedures. PMID- 22773336 TI - Multi-spectroscopic DNA interaction studies of sunset yellow food additive. AB - The use of food dyes is at least controversial due to their essential role. Synthetic color food additives occupy an important place in the food industry. Moreover many of them have been related to health problems mainly in children that are considered the most vulnerable group. The purpose of this work is to present spectrophotometric methods to analyze the interaction of native calf thymus DNA (CT-DNA) with sunset yellow (SY) at physiological pH. Considerable hyperchromism and no red shift with an intrinsic binding constant of 7 * 10(4 )M( 1) were observed in UV absorption band of SY. Binding constants of DNA with complex were calculated at different temperatures. Slow increase in specific viscosity of DNA, induced circular dichroism spectral changes, and no significant changes in the fluorescence of neutral red-DNA solutions in the presence of SY suggest that this molecule interacts with CT-DNA via groove binding mode. Furthermore, the enthalpy and entropy of the reaction between SY and CT-DNA showed that the reaction is exothermic and enthalpy favored (?H = -58.19 kJ mol( 1); DeltaS = -274.36 kJ mol(-1) ) which are other evidences to indicate that van der Waals interactions and hydrogen bonding are the main running forces in the binding of the mentioned molecule and mode of interaction with DNA. PMID- 22773337 TI - Angiotensin-converting enzyme gene deletion allele increases the risk of left ventricular hypertrophy: evidence from a meta-analysis. AB - Large panels of studies have examined the association between angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk for left ventricular hypertrophy (LVH), yet with inconclusive results. We therefore sought to evaluate this association via a comprehensive meta-analysis. A random effects model was applied irrespective of between-study heterogeneity. Data and study quality were independently assessed by two investigators. Total 52 studies encompassing 3,663 case-patients and 8,953 controls were meta-analyzed. Overall results indicated that carriers homozygous for DD genotype conferred 1.59 times (95 % confidence interval [95 % CI]: 1.31-1.92; P < 0.0005) more likely to develop LVH compared with those with II genotype, accompanying moderate evidence of heterogeneity (I (2) = 49.0 %). In subgroup analyses by ethnicity, DD homozygotes had a 90 % (95 % CI: 1.42-2.53; P < 0.0005) increased risk in East Asians, but merely a 33 % (95 % CI: 1.03-1.73; P = 0.032) increased risk in Caucasians. Moreover, differences in source of controls, cutoff for the definition of hypertension, and diagnostic method of LVH were also regarded as potential sources of heterogeneity. Further, the risk estimate associated with D allele was more pronounced in studies involving males (odds ratio [OR] = 1.47; 95 % CI: 1.2-1.8; P < 0.0005) and untreated subjects (OR = 1.39; 95 % CI: 1.2-1.62; P < 0.0005). The magnitude of publication bias was greatly improved in homozygous subgroups. Taken together, our results demonstrated significant association of ACE gene I/D polymorphism with LVH risk, especially in East Asians, and this association was more pronounced in studies involving males and untreated subjects. PMID- 22773338 TI - Structural investigations on YbRh2Si2: from the atomic to the macroscopic length scale. AB - YbRh2Si2 has advanced to a prototype material for investigating physics related to the Kondo effect. An optimization of the synthesis resulted in single crystals of extraordinary crystalline quality. At the atomic scale, we utilize scanning tunneling microscopy to study the topography of cleaved single crystals. A structural and chemical analysis was conducted by highly accurate x-ray diffraction and wavelength dispersive x-ray spectroscopy measurements. The latter indicate a homogeneity range of the YbRh2Si2 phase between approximately 40.0 40.2 at.% Rh. For our high-quality samples the number of defects found on the atomic scale (of the order of 0.3% of the visible lattice sites) is in quantitative agreement with a very small off-stoichiometry within this homogeneity range. Comparing our results for these samples allows an assignment of the structural defects observed at the cleaved surfaces to Rh occupying Si sites and, even less numerous Si in Rh sites. Such an analysis is hampered for samples of lesser quality, but there seem to be numerous empty Si-sites. Based on these observations the results of scanning tunneling spectroscopy can be analyzed in further detail and provide insight into the Kondo physics. PMID- 22773339 TI - Complement genetics, deficiencies, and disease associations. AB - The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics. PMID- 22773341 TI - Ultra-structural study of insulin granules in pancreatic beta-cells of db/db mouse by scanning transmission electron microscopy tomography. AB - Insulin granule trafficking is a key step in the secretion of glucose-stimulated insulin from pancreatic beta-cells. The main feature of type 2 diabetes (T2D) is the failure of pancreatic beta-cells to secrete sufficient amounts of insulin to maintain normal blood glucose levels. In this work, we developed and applied tomography based on scanning transmission electron microscopy (STEM) to image intact insulin granules in the beta-cells of mouse pancreatic islets. Using three dimensional (3D) reconstruction, we found decreases in both the number and the grey level of insulin granules in db/db mouse pancreatic beta-cells. Moreover, insulin granules were closer to the plasma membrane in diabetic beta-cells than in control cells. Thus, 3D ultra-structural tomography may provide new insights into the pathology of insulin secretion in T2D. PMID- 22773340 TI - Functional regulation of monocyte-derived dendritic cells by microRNAs. AB - Dendritic cells (DCs) as a rare type of leukocytes play an important role in bridging the innate and adaptive immune system. A subset of DCs, monocyte-derived dendritic cells (moDCs), exists in very low numbers at steady state but become abundant in inflammatory states. These inflammation-associated DCs are potent producers of pro-inflammatory cytokines and potent inducers of T helper differentiation. They behave as a "double-edge" sword so that they not only mediate protective immunity but also immuno-pathology. It is still incompletely understood how their function is regulated. Emerging evidence indicates that microRNAs (miRNAs), as a new class of gene regulators, potently regulate the function of moDCs. Here we summarize recent progress in this area. PMID- 22773342 TI - Prioritization of candidate genes for attention deficit hyperactivity disorder by computational analysis of multiple data sources. AB - Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder characterized by hyperactivity, inattention and increased impulsivity. In recent years, a large number of genetic studies for ADHD have been published and related genetic data has been accumulated dramatically. To provide researchers a comprehensive ADHD genetic resource, we previously developed the first genetic database for ADHD (ADHDgene). The abundant genetic data provides novel candidates for further study. Meanwhile, it also brings new challenge for selecting promising candidate genes for replication and verification research. In this study, we surveyed the computational tools for candidate gene prioritization and selected five tools, which integrate multiple data sources for gene prioritization, to prioritize ADHD candidate genes in ADHDgene. The prioritization analysis resulted in 16 prioritized candidate genes, which are mainly involved in several major neurotransmitter systems or in nervous system development pathways. Among these genes, nervous system development related genes, especially SNAP25, STX1A and the gene-gene interactions related with each of them deserve further investigations. Our results may provide new insight for further verification study and facilitate the exploration of pathogenesis mechanism of ADHD. PMID- 22773344 TI - The growth of B cell receptor microcluster is a universal response of B cells encountering antigens with different motion features. AB - B lymphocyte cell senses and acquires foreign antigens through clonal distributed B cell receptors (BCRs) expressed on the surface of plasma membrane. The presentation formats of antigens are quite diverse. Based on their Brownian diffusion mobility, there are three forms: free mobile soluble antigens, lateral mobile membrane bound antigens, and fixed immobile antigens. Here, using high resolution high speed live cell imaging approaches, we provide evidence that BCR microclusters are formed on the surface of B cells shortly after B cell's encountering of antigens with each format of motion features. Through high speed live cell imaging, we determine that these BCR microclusters show dynamic growth feature and by doing so function as the basic platforms for B cells to acquire the antigens. We propose that the formation and dynamic growth of BCR microcluster is a universal mechanism for B cell to response to antigens with diverse motion features. PMID- 22773343 TI - Curcumin induces differentiation of embryonic stem cells through possible modulation of nitric oxide-cyclic GMP pathway. AB - Curcumin, an active ingredient of dietary spice used in curry, has been shown to exhibit anti-oxidant, anti-inflammatory and anti-proliferative properties. Using EB directed differentiation protocol of H-9 human embryonic stem (ES) cells; we evaluated the effect of curcumin (0-20 MUmol/L) in enhancing such differentiation. Our results using real time PCR, western blotting and immunostaining demonstrated that curcumin significantly increased the gene expression and protein levels of cardiac specific transcription factor NKx2.5, cardiac troponin I, myosin heavy chain, and endothelial nitric oxide synthase during ES cell differentiation. Furthermore, an NO donor enhanced the curcumin mediated induction of NKx2.5 and other cardiac specific proteins. Incubation of cells with curcumin led to a dose dependent increase in intracellular nitrite to the same extent as giving an authentic NO donor. Functional assay for second messenger(s) cyclic AMP (cAMP) and cyclic GMP (cGMP) revealed that continuous presence of curcumin in differentiated cells induced a decrease in the baseline levels of cAMP but it significantly elevated baseline contents of cGMP. Curcumin addition to a cell free assay significantly suppressed cAMP and cGMP degradation in the extracts while long term treatment of intact cells with curcumin increased the rates of cAMP and cGMP degradation suggesting that this might be due to direct suppression of some cyclic nucleotide-degrading enzyme (phosphodiesterase) by curcumin. These studies demonstrate that polyphenol curcumin may be involved in differentiation of ES cells partly due to manipulation of nitric oxide signaling. PMID- 22773346 TI - Linkage and association of successful aging to the 6q25 region in large Amish kindreds. AB - Successful aging (SA) is a multidimensional phenotype involving living to older age with high physical function, preserved cognition, and continued social engagement. Several domains underlying SA are heritable, and identifying health promoting polymorphisms and their interactions with the environment could provide important information regarding the health of older adults. In the present study, we examined 263 cognitively intact Amish individuals age 80 and older (74 SA and 189 "normally aged") all of whom are part of a single 13-generation pedigree. A genome-wide association study of 630,309 autosomal single nucleotide polymorphisms (SNPs) was performed and analyzed for linkage using multipoint analyses and for association using the modified quasi-likelihood score test. There was evidence for linkage on 6q25-27 near the fragile site FRA6E region with a dominant model maximum multipoint heterogeneity LOD score = 3.2. The 1-LOD-down support interval for this linkage contained one SNP for which there was regionally significant evidence of association (rs205990, p = 2.36 * 10(-5)). This marker survived interval-wide Bonferroni correction for multiple testing and was located between the genes QKI and PDE10A. Other areas of chromosome 6q25-q27 (including the FRA6E region) contained several SNPs associated with SA (minimum p = 2.89 * 10(-6)). These findings suggest potentially novel genes in the 6q25-q27 region linked and associated with SA in the Amish; however, these findings should be verified in an independent replication cohort. PMID- 22773347 TI - Thoracoscopic pleural biopsy as an aid to diagnosis in pediatric tuberculosis with pleural involvement. AB - INTRODUCTION: Successful treatment of tuberculosis relies on microbiological diagnosis and drug sensitivities. Due to the pauci-bacillary nature of childhood infection, this is often not possible. We describe the successful microbiological diagnosis of tuberculosis using thoracoscopic pleural nodule biopsy. MATERIAL AND METHODS: In seven patients presenting with pulmonary tuberculosis and pleural involvement, but in whom microbiological diagnosis could not be established, thoracoscopic pleural biopsy was performed and analyzed for histology, acid-fast bacilli, polymerase chain reaction (PCR), DNA, culture, and drug sensitivities. RESULTS: In five out of the seven patients we achieved positive histology, culture, and drug sensitivities. In the remaining two patients, histology, PCR, and DNA probe were positive for tuberculosis. CONCLUSIONS: Thoracoscopic pleural biopsy is a sensitive aid to the diagnosis of pleural tuberculosis in children. PMID- 22773348 TI - Postoperative lower esophageal dilation in children following the performance of Nissen fundoplication. AB - OBJECTIVES: The purpose of this study is to study the frequency and factors associated with lower esophageal dilation (LED) after Nissen fundoplication. METHODS: This retrospective monocentric study included 288 patients who had undergone Nissen fundoplication from 1998 to 2009. The frequency of children requiring LED was assessed. The clinical characteristics of the patients at the time of fundoplication, their symptoms, and outcomes were recorded. The population with LED (group 1) was compared with the population without LED (group 2) to identify factors associated with postfundoplication LED using multivariate analysis. RESULTS: LED was required by 70 patients (24%) because of postoperative dysphagia, and 45/70 were dilated within the first 6 months. The mean age at dilation was 72 months (standard deviation [SD] 65), with an average post-Nissen delay of 9 months (SD 13). Surgical revision was required by 11 patients because of LED failure (n = 10) or postdilation perforation (n = 1). Patients who required post-Nissen dilation were significantly more frequently fed orally than those in group 2 and had more postoperative complications (dumping syndrome, surgical revision). CONCLUSIONS: A significant frequency of postfundoplication LED was observed in this pediatric population. Dilation was associated in children with preoperative feeding or postoperative complications (dumping syndrome, surgical revision). PMID- 22773350 TI - Tailgut cyst prolapsing through the anus. PMID- 22773349 TI - Operative considerations in pediatric retroperitoneal teratomas--a review. AB - BACKGROUND: Retroperitoneal teratomas account for 5% of teratomas and occur predominantly in infants. The resection of these tumors has been variously reported as easy or difficult. This report presents a series of retroperitoneal teratomas and reviews the literature focusing on the relevant operative considerations in this tumor. METHODS: A retrospective chart review from 1996 to 2011 identified five children with retroperitoneal teratomas. Clinical features, radiologic findings, operative details, and outcome were recorded. The literature was reviewed to identify operative complications for these tumors. RESULTS: Out of the five patients, four were infants. The tumor was characterized by dense adhesions in all patients, and resection was complicated by gastric and common bile duct injury. Hiatal hernia repair was required in one and spillage was seen in two patients. One patient had a staged resection after birth with colostomy, vesicostomy, and eventual death on day 12 of life. Inferior vena cava (IVC) ligation was required in one. A total of four patients were well on long-term follow-up. Review of the literature revealed that computed tomography scan while being sufficient for diagnosing a retroperitoneal teratoma is often inadequate in delineating the vascular anatomy, which is usually distorted. The IVC and the mesenteric vessels may be inseparable and require ligation. Renal vessel injury is possible, leading onto ischemia and hypertension. The tumor may be intimately adherent to the viscera in the abdomen, making resection complicated. Adequate resection is possible and necessary for cure, but not always possible with clear resection margins. Late complications include recurrence, adhesions, and hypertension. The perioperative mortality is 0 to 8% and the complication rate is 50 to 100%. CONCLUSION: Surgical resection of retroperitoneal teratomas, while being the mainstay of treatment is challenging in view of its size, adhesions, and vascular distortion. PMID- 22773351 TI - Distribution of feeding styles after pyloromyotomy among pediatric surgical training programs in North America. AB - INTRODUCTION: The feeding regimen employed after pyloromyotomy for pyloric stenosis continues to be a topic of debate and has yet to be evaluated in a prospective, randomized trial. To understand the spectrum of current feeding schedules being utilized in the various training programs, we queried the program directors or representatives about their feeding schedules. METHODS: Through the use of multiple electronic communication resources, we surveyed 47 pediatric training programs in the United States and Canada about their postpyloromyotomy feeding schedules. Questions included time to first feed, how the schedule is advanced, and criteria for stopping feeds and discharge. RESULTS: Responses were received from 34 of the 47 institutions. Six programs had variable times of delay before instituting feeding whether ad libitum (ad lib) or protocol. The average time of delay was 4.3 hours. Six programs reported both ad lib feed and protocol feeding regiments. Twelve institutions used ad lib feeding regiments. Eight started feeding without delay. Twenty-six programs including our institution currently employ a protocol-based feeding regiment. Of these programs, seven begin the protocol without delay. CONCLUSIONS: Despite retrospective evidence in support of ad lib feeds after pyloromyotomy, the majority of teaching institutions employs protocols for the postpyloromyotomy feeding schedule. There is clearly a role for a prospective, randomized trial to compare ad lib to schedule feeding. PMID- 22773353 TI - Piloluminal appendicitis. PMID- 22773352 TI - Pyeloplasty for pelvi-ureteric junction obstruction in malrotated kidneys in children. AB - PURPOSE: Pelvi-ureteric junction (PUJ) obstruction associated with malrotated kidney is very rare. In such cases, dismembered pyeloplasty poses technical difficulties. We present our experience with management of PUJ obstruction in malrotated kidneys in children and their outcomes. METHODS: Retrospective review of case notes of all children who had pyeloplasty for PUJ obstruction associated with malrotated kidneys, over a period of 7 years between January 2003 and December 2009 at our institution. RESULTS: We identified four patients, and all four patients had malrotated kidneys with a lateral and slightly inferior facing renal pelvis. Anderson and Hynes dismembered pyeloplasty with inferior pelvi ureteric anastamosis was performed in two patients (one patient with nephropexy and one patient without nephropexy), but failed to improve the drainage across the PUJ in both the patients. The remaining two patients underwent a dismembered pyeloplasty with anterior pelvi-ureteric anastamosis that resulted in a good drainage. One of the patients who had pyeloplasty with inferior pelvi-ureteric anastamosis had a redo pyeloplasty with anterior pelvi-ureteric anastamosis that restored the drainage adequately. CONCLUSION: In our experience dismembered pyeloplasty with inferior pelvi-ureteric anastamosis along with or without nephropexy has not been successful in cases of PUJ obstruction in laterally malrotated kidneys. Although the number of cases in our study is small, we have had a 100% success with dismembered pyeloplasty with anterior pelvi-ureteric anastamosis. The authors are of the opinion that this modified approach is recommended as a viable option both as a primary and salvage procedure for PUJ obstruction in laterally malrotated kidneys. PMID- 22773354 TI - Delayed repeated enema and operative findings after unsuccessful primary enema for intussusception. AB - INTRODUCTION: The purpose of this study was (1) to evaluate the role for and the potential morbidity associated with delayed repeated enema (DRE) and (2) to compare surgical findings for patients undergoing operative exploration after failed primary enema and DRE reduction attempts for intussusception. METHODS: After obtaining approval from the Internal Review Board, we completed a retrospective review of all patients treated for intussusception at a large, tertiary care pediatric hospital. We evaluated the success of primary reduction enema, DRE, and compared surgical findings after failed enema reduction. RESULTS: A total of 135 intussusceptions underwent an attempt at enema reduction following diagnosis. Of these, 83 (61.5%) intussusceptions were reduced with primary enema. Thirty-four patients (25.2%) proceeded directly to surgical exploration after a failed primary enema and 4 more patients were explored after successful reduction due to suspicion for a pathologic lead point. Thirty-four of these operations were therapeutic. In this, four patients had a negative exploration; eight patients required a bowel resection due to necrotic bowel, perforation, or persistence of an irreducible intussusception. Eighteen patients underwent a DRE after a failed primary enema. Two DREs revealed the intussusception had completely reduced before the study, and 11 DREs were successful in reducing persistent intussusceptions. Five patients underwent operative exploration after a failed DRE and were all found to have a persistent intussusception which was successfully reduced intraoperatively. There were no negative laparotomies, pathologic lead points, or instances of necrotic bowel or perforation in patients explored following unsuccessful DRE and no bowel resections were required. CONCLUSIONS: The use of DRE in select patients with persistence of an intussusception may result in successful subsequent reduction with no apparent increase in morbidity. A DRE may lead to improved outcomes for patients with intussusception through avoidance of unnecessary surgical reductions and negative explorations. PMID- 22773355 TI - Fracture healing of an osteodysplastic femur in a microcephalic osteodysplastic primordial dwarfism II (MOPD II) patient: a case report. PMID- 22773356 TI - False aneurysm of the brachial artery secondary to K-wire fixation of a supracondylar fracture of the humerus. PMID- 22773357 TI - Cystic adventitial disease of popliteal artery in a boy younger than 6 years old. PMID- 22773358 TI - Efficacy of amlodipine/olmesartan +/- hydrochlorothiazide in patients uncontrolled on prior calcium channel blocker or angiotensin II receptor blocker monotherapy. AB - INTRODUCTION: While monotherapy is often recommended as initial treatment, most patients require dose escalation and add-on agents to achieve their blood pressure (BP) goal. This secondary analysis evaluated the efficacy and safety of initiating patients on a regimen of fixed-dose amlodipine (AML)/olmesartan medoxomil (OM) +/- hydrochlorothiazide (HCTZ) who were uncontrolled on prior monotherapy with a calcium channel blocker (CCB) or angiotensin II receptor blocker (ARB). METHODS: Patients uncontrolled on prior monotherapy with CCB or ARB therapy were initiated on AML/OM 5/20 mg and up-titrated every 4 weeks to AML/OM 5/40 mg, AML/OM 10/40 mg, AML/OM 10/40 + HCTZ 12.5 mg, and AML/OM 10/40 + HCTZ 25 mg. Patients were up-titrated to a higher AML/OM dose if mean seated cuff BP (SeBP) was >=120/70 mmHg, and up-titrated to any HCTZ dose if mean SeBP was >=125/75 mmHg. The primary efficacy endpoint was the cumulative proportion of patients achieving a seated cuff systolic BP (SeSBP) goal of <140 mmHg (<130 mmHg for patients with diabetes) after 12 weeks. Secondary endpoints included mean change from baseline in SeBP and ambulatory BP, ambulatory BP target achievement, and safety. RESULTS: For the prior CCB (n = 118; baseline SeBP: 153.4/91.5 mmHg) and ARB (n = 237; 154.6/92.6 mmHg) groups, SeSBP goal achievement after 12 weeks was 72.7% and 76.9%, respectively. Mean changes (+/- SE) from baseline in SeBP were dose proportional for prior CCB and ARB patients, ranging from -9.9 (+/- 1.25)/-5.8 (+/- 0.83) mmHg and -13.9 (+/- 0.79)/-7.6 (+/- 0.47) mmHg at the AML/OM 5/20 mg dose, respectively, to -21.8 (+/- 1.68)/-11.6 (+/-.12) mmHg and 26.2 (+/- 1.31)/-15.0 (+/- 0.86) mmHg at the AML/OM 10/40 mg + HCTZ 25 mg dose (P < 0.0001 for all). CONCLUSION: An AML/OM-based titration regimen was efficacious in achieving BP goal in patients uncontrolled on prior monotherapy with a CCB or ARB. PMID- 22773359 TI - Functional gastrointestinal symptoms in children with anxiety disorders. AB - This study examined the incidence and correlates of functional gastrointestinal symptoms in children with anxiety disorders. Participants were 6-13 year old children diagnosed with one or more anxiety disorders (n = 54) and non-clinical control children (n = 51). Telephone diagnostic interviews were performed with parents to determine the presence and absence of anxiety disorders in children. Parents completed a questionnaire that elicited information about their child's gastrointestinal symptoms associated with functional gastrointestinal disorders in children, as specified by the paediatric Rome criteria (Caplan et al., Journal of Pediatric Gastroenterology & Nutrition, 41, 296-304, 2005a). Parents and children also completed a symptom severity measure of anxiety. As expected, children with anxiety disorders were significantly more likely to have symptoms of functional gastrointestinal disorders (FGID), compared to children without anxiety disorders. That is, 40.7 % of anxious children had symptoms of a FGID compared to 5.9 % of non-anxious control children. Children with anxiety disorders were significantly more likely to have symptoms of functional constipation, and showed a trend for a higher incidence of irritable bowel syndrome symptoms compared to non-anxious control children. Furthermore, higher anxiety symptom severity was characteristic of anxious children with symptoms of FGID, compared to anxious children without FGID symptoms and non-anxious control children. Also, children with anxiety disorders, regardless of FGID symptoms, were more likely to have a biological family member, particularly a parent or grandparent, with a gastrointestinal problem, compared to non-anxious control children. The high incidence of FGID symptoms in children with anxiety disorders warrants further research on whether gastrointestinal symptoms reduce following psychological treatments for childhood anxiety disorders, such as cognitive behavioural therapy. PMID- 22773360 TI - Testing informant discrepancies as predictors of early adolescent psychopathology: why difference scores cannot tell you what you want to know and how polynomial regression may. AB - Multiple informants commonly disagree when reporting child and family behavior. In many studies of informant discrepancies, researchers take the difference between two informants' reports and seek to examine the link between this difference score and external constructs (e.g., child maladjustment). In this paper, we review two reasons why difference scores cannot serve as unambiguous predictors of outcomes. Further, we use polynomial regression analyses to both test the validity of difference scores and provide a more direct test of the hypothesis that discrepancies in parent and child reports predict child psychopathology. Data from 218 parent-adolescent dyads (M adolescent age = 11.5 years, 51 % female; 49 % European American, 47 % African American) were used to predict adolescent-reported antisocial behavior and depression from parent and adolescent reports of parent-adolescent conflict, parental knowledge, parental acceptance, adolescent rule-breaking behavior, and adolescent pubertal development. Results demonstrate that analyses using difference scores do not provide valid tests of the utility of informant discrepancies in predicting adolescent psychosocial maladjustment. However, interaction terms in polynomial regression analyses provide evidence that informant discrepancies predict child psychopathology. Parent-adolescent informant discrepancies predict adolescent psychopathology but researchers should avoid using difference scores to measure informant discrepancies. Polynomial regression analyses provide more comprehensive and accurate tests of whether informant discrepancies predict child and adolescent psychopathology. PMID- 22773361 TI - Construct validity of ADHD/ODD rating scales: recommendations for the evaluation of forthcoming DSM-V ADHD/ODD scales. AB - Exploratory structural equation modeling (SEM) was applied to a multiple indicator (26 individual symptom ratings) by multitrait (ADHD-IN, ADHD-HI and ODD factors) by multiple source (mothers, fathers and teachers) model to test the invariance, convergent and discriminant validity of the Child and Adolescent Disruptive Behavior Inventory with 872 Thai adolescents and the ADHD Rating Scale IV and ODD scale of the Disruptive Behavior Inventory with 1,749 Spanish children. Most of the individual ADHD/ODD symptoms showed convergent and discriminant validity with the loadings and thresholds being invariant over mothers, fathers and teachers in both samples (the three latent factor means were higher for parents than teachers). The ADHD-IN, ADHD-HI and ODD latent factors demonstrated convergent and discriminant validity between mothers and fathers within the two samples. Convergent and discriminant validity between parents and teachers for the three factors was either absent (Thai sample) or only partial (Spanish sample). The application of exploratory SEM to a multiple indicator by multitrait by multisource model should prove useful for the evaluation of the construct validity of the forthcoming DSM-V ADHD/ODD rating scales. PMID- 22773363 TI - Confinement of chiral magnetic modulations in the precursor region of FeGe. AB - We report on magnetic susceptibility and specific heat measurements of the cubic helimagnet FeGe in external magnetic fields and temperatures near the onset of long-range magnetic order at TC = 278.2(3) K. Pronounced anomalies in the field dependent chiac(H) data as well as in the corresponding imaginary part chi''ac(H) reveal a precursor region around TC in the magnetic phase diagram. The occurrence of a maximum at T0 = 279.6 K in the zero-field specific heat data indicates a second-order transition into a magnetically ordered state. A shoulder evolves above this maximum as a magnetic field is applied. The field dependence of both features coincides with crossover lines from the field-polarized to the paramagnetic state deduced from chiac(T) at constant magnetic fields. The experimental findings are analyzed within the standard Dzyaloshinskii theory for cubic helimagnets. The remarkable multiplicity of modulated precursor states and the complexity of the magnetic phase diagram near the magnetic ordering are explained by the change of the character of solitonic inter-core interactions and the onset of specific confined chiral modulations in this area. PMID- 22773362 TI - New approaches to genetic counseling and testing for Alzheimer's disease and frontotemporal degeneration. AB - The discovery of new autosomal dominant and susceptibility genes for Alzheimer's disease (AD) and frontotemporal degeneration (FTD) is revealing important new information about the neurodegenerative process and the risk for acquiring these diseases. It is becoming increasingly clear that both the mechanisms that drive these diseases and their phenotypes overlap. New technologies will assist access to genetic testing but may increase difficulty with genetic test interpretation. Thus, the process of genetic counseling and testing for these diseases is becoming more complex. This article will review current knowledge on the genetics of AD and FTD and suggest clinical guidelines for helping families to navigate through these complexities. The implications of future discoveries will be offered. PMID- 22773364 TI - Has "respiratory coaching" before deep inspiration an impact on the incidence of transient contrast interruption during pulmonary CT angiography? AB - PURPOSE: To evaluate if respiratory coaching performed prior to CT pulmonary angiography (CTPA) image acquisition has an impact on the occurrence of transient interruption of contrast (TIC) phenomenon. MATERIALS AND METHODS: Two hundred and thirty-one consecutive patients with suspected pulmonary embolism (PE) were referred for CTPA. They were randomised into two groups, with or without respiratory coaching (groups A and B, respectively). Those patients who were deemed not able to be coached were not randomised and were assigned to a third group (C). Two radiologists evaluated the degree of enhancement of the pulmonary arteries and the presence and grade of TIC. The chi(2) test was used to compare differences among groups in occurrence and grade of this phenomenon. RESULTS: There were no significant differences in the presence of any grade of TIC among the three groups, with 30 positive cases (32%) in group A, 33 (35%) in group B, and 12 (27%) in group C (P = 0.61). When TIC was graded and divided into significant or not, the different groups also did not differ significantly. CONCLUSION: Performing respiratory coaching before CTPA had no statistically significant effect on the incidence and severity of TIC in this prospective randomised study. MAIN MESSAGES: * Significant transient interruption of contrast appears in 12% of pulmonary CT angiograms. * Severe transient interruption of contrast leading to nondiagnostic tests appears in 2% of studies. * In our study respiratory coaching has no impact on the incidence of transient interruption of contrast. PMID- 22773366 TI - Treatment of obesity by catgut embedding: an evidence-based systematic analysis. PMID- 22773365 TI - Mild cognitive impairment in older adults. AB - Mild cognitive impairment (MCI) is the intermediate stage between the cognitive changes of normal aging and dementia. MCI is important because it constitutes a high risk group for dementia. Ideally, prevention strategies should target individuals who are not even symptomatic. Indeed, the field is now moving towards identification of asymptomatic individuals who have underlying Alzheimer's disease (AD) pathology that can be detected using biomarkers and neuroimaging technologies. To this effect, the Alzheimer's Association and the National Institute on Aging have developed a new classification scheme that has categorized AD into a preclinical phase (research category), MCI due to AD, and dementia of Alzheimer's type. However, there are also ongoing research studies to understand high-risk groups for non-Alzheimer's dementia. PMID- 22773367 TI - Low-entry-point method for chorda tympani nerve preservation during middle ear surgery. PMID- 22773368 TI - Attention-deficit hyperactivity disorder and cardiac vagal control: a systematic review. AB - Attention-deficit hyperactivity disorder (ADHD) is characterized by behavioural disinhibition, deficient emotional self-regulation, inattention, and hyperactivity. The constellation of deficits found in children with ADHD implicates autonomic dysregulation characterized by deficient control of the heart by parasympathetic influences. While it is generally assumed that autonomic regulation of the heart is impaired during ADHD, the information pertaining to this dysregulation is limited. A systematic review of three databases was conducted between January and March 2012 for peer reviewed publications examining the relationship between cardiac vagal control (CVC) and ADHD without comorbid psychopathology. 19 articles were reviewed with only 6 meeting inclusion criteria. Findings were not unanimous but suggested that children with unmedicated ADHD experienced lower levels of CVC than did healthy controls. It was difficult to evaluate whether children with ADHD exhibited a different pattern of withdrawal and application of CVC than did normal controls. Findings suggested CVC reactivity depended on the task employed but children with ADHD experienced dampened CVC reactivity during tasks that involved self-regulation and emotion regulation. Finally, medication acted to correct the autonomic imbalance experienced by children with ADHD but did not bring this imbalance into normal levels. Given that so few studies were identified, no firm conclusions can be made, and there is a clear need for additional research in this area. Recommendations for future research are discussed. PMID- 22773369 TI - Antiferromagnetism in metals: from the cuprate superconductors to the heavy fermion materials. AB - The critical theory of the onset of antiferromagnetism in metals, with concomitant Fermi surface reconstruction, has recently been shown to be strongly coupled in two spatial dimensions. The onset of unconventional superconductivity near this critical point is reviewed: it involves a subtle interplay between the breakdown of fermionic quasiparticle excitations on the Fermi surface and the strong pairing glue provided by the antiferromagnetic fluctuations. The net result is a logarithm-squared enhancement of the pairing vertex for generic Fermi surfaces, with a universal dimensionless coefficient independent of the strength of interactions, which is expected to lead to superconductivity at the scale of the Fermi energy. We also discuss the possibility that the antiferromagnetic critical point can be replaced by an intermediate 'fractionalized Fermi liquid' phase, in which there is Fermi surface reconstruction but no long-range antiferromagnetic order. We discuss the relevance of this phase to the underdoped cuprates and the heavy fermion materials. PMID- 22773370 TI - Advances in neuroendocrine mechanisms. PMID- 22773371 TI - Environmental influences that alter the stress circuitry. PMID- 22773372 TI - Nerve growth factor induces the expression of chaperone protein calreticulin in human epithelial ovarian cells. AB - Epithelial ovarian cancer is highly angiogenic and high expression of Nerve Growth Factor (NGF), a proangiogenic protein. Calreticulin is a multifunctional protein with anti-angiogenic properties and its translocation to the tumor cell membrane promotes recognition and engulfment by dendritic cells. The aim of this work was to evaluate calreticulin expression in human normal ovaries, benign and borderline tumors, and epithelial ovarian cancer samples and to evaluate whether NGF regulates calreticulin expression in human ovarian surface epithelium and in epithelial ovarian cancer cell lines. Calreticulin mRNA and protein levels were analyzed using RT-PCR, Western blot and immunohistochemistry in 67 human ovarian samples obtained from our Institution. Calreticulin expression induced by NGF stimulation in cell lines was evaluated using RT-PCR, Western blot and immunocytochemistry. We found a significant increase of calreticulin mRNA levels in epithelial ovarian cancer samples as compared to normal ovaries, benign tumors, and borderline tumors. Calreticulin protein levels, evaluated by Western blot, were also increased in epithelial ovarian cancer with respect to benign and borderline tumors. When HOSE and A2780 cell lines were stimulated with Nerve Growth Factor, we found an increase in calreticulin protein levels compared to controls. This effect was reverted by GW441756, a TRKA specific inhibitor. These results suggest that NGF regulates calreticulin protein levels in epithelial ovarian cells through TRKA receptor activation. PMID- 22773373 TI - Effects of salinomycin on human ovarian cancer cell line OV2008 are associated with modulating p38 MAPK. AB - This study investigated the anticancer effect and mechanism of salinomycin, a selective inhibitor of cancer stem cell, on human ovarian cancer cell line OV2008 in vitro and in vivo. The growth inhibitory effect of salinomycin on ovarian cancer cell line OV2008 was determined by measuring cell viability using the resazurin reduction assay. Apoptotic nuclear morphology was visualized by 4,6 diamino-2-phenylindole staining technique. The percentages of apoptotic cells and cell cycle parameters were detected by flow cytometry. The activity of p38 mitogen-activated protein kinase (p38 MAPK) was analyzed by Bio-Plex phosphoprotein assay. In vivo activity of salinomycin was assayed through tumor growth. Salinomycin caused concentration- (0.01-200 MUM) and time-dependent (24 72 h) growth inhibitory effects in OV2008. Cell nuclear morphology observations showed that salinomycin-treated OV2008 cells displayed typical apoptotic characteristics. Salinomycin significantly increased the percentages of apoptotic cells in OV2008, showing a concentration- and time-dependent manner. There was no cell cycle arrest in the G1/G0, S, and G2/M phases between salinomycin-treated cells and control cells. Salinomycin also enhanced the phosphorylation of p38 MAPK. Moreover, salinomycin significantly inhibited the growth of the ovarian xenograft tumors. Salinomycin exhibited significant growth inhibition and induction of apoptosis in the human ovarian cancer cell line OV2008. The data suggested that salinomycin-induced apoptosis in OV2008 might be associated with activating p38 MAPK and merits further investigations. PMID- 22773374 TI - Helicobacter pylori, a carcinogen, induces the expression of melanoma antigen encoding gene (Mage)-A3, a cancer/testis antigen. AB - Cancer/testis antigens (CTAs) are known to be expressed in various cancer types but are minimally or not expressed in normal tissues except for germline tissues. CTAs are attractive targets for cancer immunotherapy and diagnosis because of their restricted expression. The mechanisms of CTAs expression are unclear because the inducers of CTAs expression remain to be elucidated. We hypothesized that carcinogens may induce the cellular expression of CTAs. To prove this, we attempted to inoculate Helicobacter pylori, a known carcinogen, in Meth-A cells, normal gastric cells, and normal splenocytes and induce the expression of a CTA. Melanoma antigen-encoding gene (Mage)-A3, one of the CTAs, was not expressed in both normal cells but in Meth-A cells inoculated with H. pylori. Furthermore, we performed limiting dilution using Meth-A cells inoculated with H. pylori and established derivative clone from Meth-A designated as Meth-A/pylori/3C3 which permanently express Mage-A3 after excluding H. pylori. We herein report the first successful induction of a CTA in a cell line via exposure to a carcinogenic agent. Furthermore, the establishment of Meth-A/pylori/3C3, which is Meth-A expressing Mage-A3, is considered to contribute to the resolution of the mechanism of CTAs expression. PMID- 22773375 TI - Current concept of spondyloarthritis: special emphasis on early referral and diagnosis. AB - Ankylosing spondylitis is the prototype of inflammatory rheumatic diseases grouped under the term spondyloarthritis or spondyloarthropathy (SpA). New classification criteria for SpA have now been proposed; the patients are subgrouped into (1) a predominantly axial disease, termed axial SpA, which includes AS, and (2) peripheral SpA. There is an unacceptable delay in the diagnosis of axial SpA, and there are still no validated diagnostic criteria for SpA. An early diagnosis has now become increasingly important because effective therapies in the form of TNF antagonists have become available that are even more effective if used in early stages of the disease. Therefore, new strategies are being proposed that will assist in making an early diagnosis and will also help primary care physicians in screening for these patients so that they can be referred to rheumatologists when the disease is still in its early stages. These strategies may be less efficient for early referral of children and adolescents suffering from SpA, because their most important early manifestation is not inflammatory back pain but peripheral arthritis and enthesitis. There is, therefore, a need to develop a different strategy for children and adolescents with SpA through the use, preferably, of the ASAS/EULAR classification criteria for peripheral SpA, more so than the classification criteria for axSpA. PMID- 22773376 TI - Racial and ethnic disparities in rheumatoid arthritis. AB - Racial and ethnic health disparities are a national health issue. They are well described in other chronic diseases, but in rheumatoid arthritis (RA), research into their causes, outcomes, and elimination is in its early stages. Health disparities occur in a complex milieu, with system-level, provider-level, and individual-level factors playing roles. Dissecting the overlapping aspects of race/ethnicity, socioeconomic variables, and how their individual components combine to explain the magnitude of disparities in RA can be challenging. Recent research has focused on the extent to which treatment preferences, adherence, trust in physicians, patient-physician communication, health literacy, and depression have contributed to observed disparities in RA. Practicing evidence based medicine, improving patient-physician communication skills, reducing language and literacy barriers, improving adherence to therapies, raising awareness of racial/ethnic disparities, and recognizing comorbidities such as depression are steps clinicians may take to help eliminate racial/ethnic disparities in RA. PMID- 22773377 TI - Stigma in attention deficit hyperactivity disorder. AB - Attention deficit hyperactivity disorder (ADHD) is a frequently diagnosed disorder in child- and adulthood with a high impact affecting multiple facets of social life. Therefore, patients suffering from ADHD are at high risk to be confronted with stigma, prejudices, and discrimination. A review of the empirical research in the field of ADHD with regard to stigma was performed. The findings of investigations in this field were clustered in different categories, including stigma in children with ADHD, stigma in adults with ADHD, stigma in relatives or in people close to a patient with ADHD, and the influence of stigma on authorities' attitudes toward patients with ADHD. Variables identified to contribute to stigma in ADHD are public's uncertainty concerning the reliability/validity of an ADHD diagnosis and the related diagnostic assessment, public's perceived dangerousness of individuals with ADHD, socio-demographical factors as age, gender, and ethnicity of the respondent or the target individual with ADHD, stigmatization of ADHD treatment, for example public's skepticism toward ADHD medication and disclosure of diagnostic status as well as medication status of the individual with ADHD. The contribution of stigma associated with ADHD can be conceptualized as an underestimated risk factor, affecting treatment adherence, treatment efficacy, symptom aggravation, life satisfaction, and mentally well-being of individuals affected by ADHD. Public as well as health professionals' concepts about ADHD are highly diverse, setting individuals with an ADHD diagnosis at greater risk to get stigmatized. PMID- 22773378 TI - Superconducting gap structure of the 115s revisited. AB - Density functional theory calculations of the electronic structure of Ce- and Pu based heavy fermion superconductors in the so-called 115 family are performed. The gap equation is used to consider which superconducting order parameters are most favorable assuming a pairing interaction that is peaked at (pi, pi, qz)-the wavevector for the antiferromagnetic ordering found in close proximity. In addition to the commonly accepted dx2-y2 order parameter, there is evidence that an extended s-wave order parameter with nodes is also plausible. We discuss whether these results are consistent with current observations and possible measurements that could help distinguish between these scenarios. PMID- 22773379 TI - Effects of a moderate physical training on the leptin synthesis by adipose tissue of adult rats submitted to a perinatal low-protein diet. AB - The aim of the study was to verify if moderate physical training affects leptin content in visceral and subcutaneous adipose tissue of adult rats subjected to a low-protein diet during the perinatal period. Male Wistar rats were divided into 2 groups according to their mother's diet during gestation and lactation: control (17% casein, C, n=12) and low-protein (8% casein, LP, n=12). On postnatal day 60, half of each group was submitted to moderate physical training (8 wks, 5 d . wk - 1, 60 min . d - 1, at 70% of VO2max, T) or not. After the physical training period, visceral and subcutaneous adipose tissues were removed. Leptin content was evaluated by western blotting. Starting from the fifth week on, T pups showed a reduction in the body weight. Similarly, LP+T offspring showed a lower body weight starting from the sixth week on. Western blotting analysis showed that leptin content in the visceral tissue was higher in the LP rats (p<0.01) and it was reversed in LP+T. No difference was found in the subcutaneous tissue. Moderate physical training attenuated the effects of a perinatal low-protein diet on the leptin content in visceral adipose tissue in adult offspring. PMID- 22773380 TI - The water table: the shifting foundation of life on land. AB - Hyperarid, arid, and semi-arid lands represent over a third of the Earth's land surface, and are home to over 38 % of the increasing world population. Freshwater is a limiting resource on these lands, and withdrawal of groundwater substantially exceeds recharge. Withdrawals of groundwater for expanding agricultural and domestic use severely limit water availability for groundwater dependent ecosystems. We examine here, with emphasis on quantitative data, case histories of groundwater withdrawals at widely differing scales, on three continents, that range from the impact of a few wells, to the outcomes of total appropriation of flow in a major river system. The case histories provide a glimpse of the immense challenge of replacing groundwater resources once they are severely depleted, and put into sharp focus the question whether the magnitude of the current and future human, economic, and environmental consequences and costs of present practices of groundwater exploitation are adequately recognized. PMID- 22773381 TI - Letter to the editor. PMID- 22773382 TI - Frequency and predictors of renal artery stenosis in hypertensive patients undergoing coronary angiography. AB - Renal artery stenosis (RAS) and coronary artery disease share common risk factors. We investigated the frequency and predictors of RAS among hypertensive patients who underwent elective coronary angiography. A total of 832 hypertensive patients underwent coronary and renal angiography at the same session. Renal artery stenosis was classified as mild, moderate, or severe. The study population consisted of 4 groups; 71.1% with normal renal arteries, 12.5% with mild, 8.9% with moderate, and 7.5% with severe RAS. The prevalence of significant (>=50%) RAS was 16.3%. The Gensini score showed a stepwise rise with increasing severity of RAS. Age, duration of hypertension, estimated glomerular filtration rate, Gensini score, and multivessel disease were independent predictors for the presence of RAS. Hypertensive patients with those risk factors might need detailed investigation for RAS which may affect their prognosis. PMID- 22773383 TI - Severity of coronary artery disease affects prognosis of patients with peripheral artery disease. AB - It remains unclear whether severity of coronary artery disease (CAD) affects the prognosis of patients with peripheral artery disease (PAD). In this retrospective, multicenter study, we analyzed 537 consecutive patients with symptomatic PAD who underwent both peripheral artery revascularization and coronary angiography (CAG) prior to revascularization. We classified patients into 3 groups based on CAG: no-CAD group, intermediate CAD group (1-2 diseased vessels), and triple-vessel disease (TVD) group. We evaluated clinical outcome including all-cause death, major adverse cardiac events (MACEs), and amputation. The no-CAD, intermediate CAD, and TVD groups comprised 204, 268, and 65 patients, respectively. Mean follow-up duration was 952 +/- 497 days. Freedom from any adverse outcome was highest in the no-CAD group and lowest in the TVD group (all cause death: 86% vs 77% vs 65%, P = .043; MACE: 95% vs 87% vs 78%, P = .044; amputation: 96% vs 92% vs 83%, P = .0015). Severity of CAD affected prognosis of patients with PAD. PMID- 22773384 TI - Full reconstitution of human platelets in humanized mice after macrophage depletion. AB - Cotransplantation of human fetal thymic tissue and CD34(+) fetal liver cells in nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) or NOD/SCID/gammac(-/-) mice results in the development of multilineage human hematopoietic cells. In this study, we show that these humanized mice had extremely low levels of human platelets. The presence of human megakaryocytes at a normal concentration in the bone marrow suggests that human megakaryocytic differentiation occurred efficiently in these mice. Rapid increase in human platelets in blood to levels comparable with those of human peripheral blood mononuclear cells (PBMCs) after macrophage depletion indicates that mouse macrophages are responsible for the poor human platelet reconstitution in humanized mice. In support of this possibility, human platelets were rapidly rejected after infusion into untreated mice, but persisted in macrophage-depleted mice. These findings indicate that inhibition or depletion of recipient mouse macrophages may provide a useful means for evaluating human thrombopoiesis and platelet function in vivo using immunodeficient mice. PMID- 22773385 TI - The race for the prize: T-cell trafficking strategies for optimal surveillance. AB - The initiation of T-cell responses requires rare precursors to locate a draining lymph node (dLN) and encounter dendritic cells (DCs) presenting peptide-major histocompatibility complexes (pMHCs). To locate this needle in the haystack rapidly, T cells face an optimization problem-what is the most efficient trafficking strategy for surveillance and recirculation through blood? Two extremes are scanning low numbers of DCs per node with frequent recirculation, or meticulous surveillance with infrequent recirculation. Naive T cells also require stimulation by self-pMHCs. To enable efficient location of both foreign and self, has evolution settled on an optimum time for T cells to spend surveying each lymph node? Using a data-driven mathematical model, we show the most efficient strategy for detecting antigen in a dLN depends on its abundance. Detection of low-density antigen is optimized with systemically slow transit. In contrast, at high densities or if dLN egress is restricted, rapid transit through other nodes is optimal. We argue that blood-lymph recirculation dynamics facilitate a trade off, and are consistent with dominant roles for the very early detection of rare foreign antigens in a dLN, and the efficient accumulation of signals from systemically distributed self-antigens. PMID- 22773386 TI - Correlation between NIH composite skin score, patient-reported skin score, and outcome: results from the Chronic GVHD Consortium. AB - There are no validated criteria to measure skin response in chronic GVHD. In a prospectively assembled, multicenter cohort of patients with chronic GVHD (N = 458), we looked for correlation of change in several different scales recommended by the National Institutes of Health (NIH) Consensus with clinician and patient perception of change and overall survival. Of the clinician scales, the NIH composite 0-3 skin score was the only one that correlated with both clinician and patient perception of improvement or worsening. Of the patient-reported scales, the skin subscale of the Lee Symptom Scale was the only one that correlated with both clinician and patient perception of improvement or worsening. At study entry, NIH skin score 3 and Lee skin symptom score > 15 were both associated with worse overall survival. Worsening of NIH skin score at 6 months was associated with worse overall survival. Improvement in the Lee skin symptom score at 6 months was associated with improved overall survival. Our findings support the use of the NIH composite 0-3 skin score and the Lee skin symptom score as simple and sensitive measures to evaluate skin involvement in clinical trials as well as in the clinical monitoring of patients with cutaneous chronic GVHD. PMID- 22773387 TI - Treatment strategies in early rheumatoid arthritis and prevention of rheumatoid arthritis. AB - Data now suggest that current strategies in the treatment of rheumatoid arthritis (RA) should focus on early identification and diagnosis, followed by early initiation of DMARD therapy. Initiation of treatment in early RA-ideally, less than 3-6 months after symptom onset-improves the success of achieving disease remission and reduces joint damage and disability. While the optimal treatment regimen in early RA is unclear, use of initial DMARD mono- or combination therapy with prompt escalation to achieve low disease activity or remission is an appropriate approach. Ultimately, the goal of RA management should be the prevention of inflammatory joint disease and, thereby, prevention of disability. To date, studies have shown that pharmacologic interventions can delay progression from undifferentiated inflammatory arthritis to classifiable RA. However, further investigation is needed to identify asymptomatic individuals at high risk for future RA and to intervene early enough in the pathogenesis of RA to prevent progression to clinical disease. PMID- 22773388 TI - Jewish spirituality, depression, and health: an empirical test of a conceptual framework. AB - BACKGROUND: Little is known about the links between spirituality and mental health among Jews. PURPOSE: This study assessed trust/mistrust in God and religious coping and examined their relationships to depressive symptoms and physical health. Religious affiliation and intrinsic religiousness were examined as moderating variables and religious coping was examined as a mediator. METHOD: Anonymous internet surveys were completed by 208 Jewish women and men of diverse denominations who resided primarily in the USA. RESULTS: Trust in God and positive religious coping were associated with lower levels of depressive symptoms and mistrust in God and negative religious coping were associated with greater depressive symptoms. Intrinsic religiosity showed a small moderation effect for mistrust in God and negative religious coping in relation to depressive symptoms and for trust in God in relation to physical health. Further, positive religious coping fully mediated the link between trust in God and less depressive symptoms and negative religious coping fully mediated the relationship between mistrust in God and greater depressive symptoms. CONCLUSION: The data lend themselves to a possible integrative cognitive-coping model, in which latent core beliefs about the Divine activate coping strategies during times of distress, which in turn impact psychological health. The findings highlight the potential clinical significance of spirituality to mental health among Jews and provide a basis for future longitudinal, experimental, and treatment outcome research. PMID- 22773389 TI - Microsuction or "micropusher"-facilitating venous microvascular venous anastomosis. PMID- 22773390 TI - Nonmagnetic ground states and phase transitions in the caged compounds PrT2Zn20 (T = Ru, Rh and Ir). AB - We performed electrical resistivity rho, magnetic susceptibility chi, specific heat C and electron diffraction measurements on single-crystalline samples of PrT2Zn20 (T = Ru, Rh and Ir). The three compounds show the Van Vleck paramagnetic behavior, indicating the nonmagnetic crystalline electric field (CEF) ground states. A Schottky-type peak appears at around 14 K, irrespective of the T element, which can be moderately reproduced by a doublet-triplet model. For T = Ru, a structural transition occurs at Ts = 138 K, below which no phase transition appears down to 0.04 K. On the other hand, for T = Ir, antiferroquadrupole (AFQ) ordering arising from the nonmagnetic Gamma3 doublet takes place at TQ = 0.11 K. For T = Rh, despite a structural transition between 170 and 470 K, the CEF ground state is still the non-Kramers Gamma3 doublet. However, no phase transition due to the Gamma3 doublet was observed even down to 0.1 K. PMID- 22773391 TI - Protection of the intrahepatic biliary tree by contemporaneous portal and arterial reperfusion: results of a prospective randomized pilot study. AB - Sequential portal and arterial revascularization (SPAr) is the most common method of graft reperfusion at liver transplantation (LT), contemporaneous portal and arterial revascularization (CPAr) was used to reduce arterial ischemia to the bile ducts. Aim of this pilot study is to prospectively compare SPAr (group 1 #38) versus CPAr (group 2 #42) in 80 consecutive LTs. Biliary anastomosis was always duct to duct [T-tube in 21 % of cases (p = 0.83) in both groups]. CPAr had longer warm ischemia 61 +/- 10 versus 39 +/- 13 min, p < 0.0001, while SPAr had longer arterial ischemia 96 +/- 39 min (p = 0.0001). No PNF while DGF was encountered in 10 versus 5 % (p = 0.32). One-year graft and patient's survival were respectively 87 versus 93 % and 83 versus 88 % in groups 1 and 2 (p = 0.31 and p = 0.39). At a median follow-up of 19 +/- 8 versus 17 +/- 8 months (p = 0.24), biliary complications were 28 %, being 39 % in group 1 and 19 % in group 2 (p = 0.04). Anastomotic stenoses were present in 11 versus 12 % (p = 0.84), biliary leakage in 5 versus 5 % (p = 0.72) and intrahepatic non-anastomotic biliary strictures in 23 versus 0 % (p = 0.0008) in groups 1 and 2. CPAr is safe and feasible and reduces the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia to the intrahepatic bile ducts. PMID- 22773392 TI - Incompatible ABO-plasma exchange and its impact on patient selection in paediatric cardiac transplantation. AB - OBJECTIVES: A decade ago, the first series of ABO-incompatible heart transplants was published, with surprising and extremely promising results; drastically reduced waiting list mortalities of infants listed for heart transplantation. Essential to the procedure was the process of plasma exchange transfusion, required to reduce isohaemagglutinin titres and facilitate the crossing of ABO blood group boundaries. Since then, Great Ormond Street Hospital, London has offered ABO-incompatible heart transplants to infants who potentially would die waiting for a suitable organ. We report the results of a decade of evolving plasma exchange experience and its impact upon patient selection. METHODS: A retrospective analysis was undertaken of all elective ABO-incompatible heart transplants at Great Ormond Street Children's Hospital from January 2001 until January 2011. Data were sought on underlying conditions and demographics of the patients, the isohaemagglutinin titre before and after plasma exchange and survival figures to date. RESULTS: Twenty-one patients underwent ABO-incompatible heart transplantation, ranging from 3 to 44 months, with preoperative isohaemagglutinin titres ranging from 0 to 1:32. All patients underwent a "3 times" plasma exchange before transplantation, requiring exchange volumes of up to 3209 mL. Postoperative isohaemagglutinin titres ranged from 0 to 1:16. One patient died of causes unrelated to organ rejection. CONCLUSIONS: Our data showed that eight patients (38.1%) were older than the previously suggested 12-month cut off age. Using a combination of adult reservoir/paediatric oxygenator and extracorporeal circuit, ABO-incompatible plasma exchange transfusions can be undertaken safely using a simplified '3 times' method, reducing the circulating levels of isohaemagglutinins whilst providing minimal circuit size. This allows ABO-incompatible heart transplantation in a broader patient population than previously reported. PMID- 22773393 TI - Preoperative anemia in total joint arthroplasty: is it associated with periprosthetic joint infection? AB - BACKGROUND: Anemia is common in patients undergoing total joint arthroplasty (TJA). Numerous studies have associated anemia with increased risk of infection, length of hospital stay, and mortality in surgical populations. However, it is unclear whether and to what degree preoperative anemia in patients undergoing TJA influences postoperative periprosthetic joint infection (PJI) and mortality. QUESTIONS/PURPOSES: We therefore (1) determined the incidence of preoperative anemia in patients undergoing TJA; (2) assessed the possible association between preoperative anemia and subsequent PJI; and (3) explored the relationship between preoperative anemia with postoperative mortality. METHODS: We identified 15,722 patients who underwent TJA from January 2000 to June 2007. Anemia was defined as hemoglobin < 12 g/dL in women and hemoglobin < 13 g/dL in men. We determined the effect of preoperative anemia, demographics, and comorbidities on postoperative complications. RESULTS: Of the 15,222 patients, 19.6% presented with preoperative anemia. PJI occurred more frequently in anemic patients at an incidence of 4.3% in anemic patients compared with 2% in nonanemic patients. Thirty-day (0.4%), 90 day (0.6%), and 1-year (1.8%) mortality rates were not higher in patients with preoperative anemia. Forty-four percent of anemic patients received an allogenic transfusion compared with only 13.4% of nonanemic patients. Anemic patients had increased hospital stays averaging 4.3 days compared with 3.9 days in nonanemic patients. Anemia did not predict cardiac complications. CONCLUSION: Our data demonstrate that preoperative anemia is associated with development of subsequent PJI. Preoperative anemia was not associated with 30-day, 60-day, or 1-year mortality in this cohort. LEVEL OF EVIDENCE: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 22773394 TI - Preoperative imaging criteria for unstable osteochondritis dissecans of the capitellum. AB - BACKGROUND: The stability of an osteochondritis dissecans (OCD) lesion of the humeral capitellum may be determined by intraoperative probing with unstable lesions being displaceable. Although preoperative imaging is used to diagnose and determine treatment of these lesions, it is unclear whether unstable lesions on imaging correspond to those found intraoperatively. QUESTIONS/PURPOSES: We therefore examined the concordance between preoperative imaging and intraoperative instability and examined the imaging features of the patients who healed without surgery. METHODS: We retrospectively reviewed 61 patients who underwent OCD of the humeral capitellum surgery or nonoperative treatment. All patients had plain radiography, MRI, and/or CT scans. The presence or absence of stability was determined intraoperatively by the International Cartilage Repair Society OCD classification. We determined the sensitivity, specificity, and predictive value of various imaging findings to predict instability. RESULTS: The following preoperative imaging features were associated with intraoperative instability: a displaced fragment, epiphyseal closure of the capitellum, or a lateral epicondyle observed on radiographs; irregular contours of the articular surface or a high signal interface on T2-weighted MRI; and a displaced fragment observed on CT. Unstable lesions were more common when the epiphysis of the capitellum was closed. Intralesional segmentation was sensitive for detecting an unstable lesion, whereas displaced type on the radiographs and displaced fragment on the CT were specific. The following imaging findings were not seen in nonoperative patients: displaced type and closure of the epiphyseal line on radiographs, irregular contours of the articular surface, articular defects, and T2 high signal intensity interface between the fragments and their bed on the MRI or a displaced fragment on the CT. CONCLUSIONS: Although we found high sensitivity for some preoperative findings on imaging, none reached 100% of sensitivity. Preoperative MRI related to the intraoperative assessment of stability. LEVEL OF EVIDENCE: Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22773395 TI - Which treatment is the best for giant cell tumors of the distal radius? A meta analysis. AB - BACKGROUND: Intralesional excision and en bloc resection are used to treat giant cell tumors (GCTs) of the distal radius. However, it is unclear whether one provides lower rates of recurrences and fewer complications, and whether the use of polymethylmethacrylate (PMMA) after curettage reduces the risk of recurrence. QUESTIONS/PURPOSES: We examined whether curettage was associated with lower rates of recurrence and fewer major complications compared with en bloc excision, and whether PMMA resulted in lower rates of recurrence compared with a bone graft. METHODS: We systematically searched the literature using the criteria, "giant cell tumor" AND "curettage" OR "intralesional excision" OR "resection". Six relevant articles were identified that reported data for 80 curettage cases (PMMA, n = 49; bone graft, n = 26; no PMMA or bone grafts, n = 5) and 59 involving en bloc excision. A meta-analysis was performed using these data. RESULTS: Overall, patients in the intralesional excision group had a higher recurrence rate (relative risk [RR], 2.80; 95% CI, 1.17-6.71), especially for Campanacci grade 3 GCTs (RR, 4.90; 95% CI, 1.36-17.66), yet fewer major complications (RR, 0.21; 95% CI, 0.09-0.54) than the en bloc resection group. The use of PMMA versus bone graft did not affect the recurrence rate (RR, 0.98; 95% CI, 0.44-2.17). CONCLUSIONS: Based on data obtained from the limited number of studies available, intralesional excision appears to be more appropriate for the treatment of local lesions (e.g., grades 1 and 2) than grade 3 GCTs of the distal radius. Moreover, PMMA was not additionally effective as an adjuvant. LEVEL OF EVIDENCE: Level III, therapeutic study (systematic review). See Guidelines for Authors for a complete description of levels of evidence. PMID- 22773397 TI - Higher cefazolin concentrations with intraosseous regional prophylaxis in TKA. AB - BACKGROUND: Prophylactic antibiotics reduce the risk of deep infection after primary TKA. However, conventional systemic dosing may not provide adequate tissue concentrations against more resistant organisms such as coagulase-negative staphylococci. Regional intravenous administration of antibiotics after tourniquet inflation achieves far higher tissue concentrations but requires foot vein cannulation. The intraosseous route may offer a rapid and reliable method of regional administration. QUESTIONS/PURPOSES: We compared tissue concentrations of cefazolin achieved with systemic versus regional intraosseous administration. METHODS: Twenty-two patients undergoing primary TKA were randomized into two groups. Group 1 received 1 g cefazolin systemically 10 minutes before tourniquet inflation. Group 2 received 1 g cefazolin intraosseously in 200 mL of normal saline through a tibial cannula after tourniquet inflation and before skin incision. Subcutaneous fat and femoral bone samples were taken at set intervals during the procedure and antibiotic concentrations measured using a validated technique involving high-performance liquid chromatography. RESULTS: The overall mean tissue concentration of cefazolin in subcutaneous fat was 186 ug/g in the intraosseous group and 11 ug/g in the systemic group. The mean tissue concentration in bone was 130 ug/g in the intraosseous group and 11 ug/g in the systemic group. These differences were consistent across all sample time points throughout the procedure. CONCLUSIONS: Intraosseous regional administration can achieve concentrations of antibiotic in tissue an order of magnitude higher than systemic administration. Further work is required to determine if this translates into increased efficacy in preventing infection, particularly against coagulase negative staphylococci. PMID- 22773398 TI - An unusual foramen in the transverse process of first thoracic vertebra. AB - The presence of foramina in the transverse processes of thoracic vertebrae is not a common feature while they are the characteristic feature of cervical vertebrae. Foramina present in the transverse process of cervical vertebrae give passage to the vertebral artery-an important artery supplying the brain and spinal cord. Thoracic vertebrae typically bear facets on the body and the transverse processes for articulation with ribs. We report the presence of a complete foramen in the left transverse process of first thoracic vertebra, which is a very rare finding. The foramen was present near the root of the transverse process in alignment with the foramina transversaria of the cervical vertebrae of the same side. This variation is explained embryologically in relation to the branches of dorsal aortae in post-branchial stage of development. Knowledge of such a variation may be of great relevance for accurate interpretation of radiological pictures and for CT and MR angiographies as well as for the management of surgical procedures. PMID- 22773396 TI - Surgical technique: Second-generation bone marrow stimulation via surgical dislocation to treat hip cartilage lesions. AB - BACKGROUND: Compared to knees, hips have more bony constraint and soft tissue coverage. Thus, repair of focal cartilage defects in hips requires more invasive and technically complex surgeries than simple arthroscopy or arthrotomy. Autologous matrix-induced chondrogenesis (AMIC) is a second-generation bone marrow stimulation technique. Improvement in Tegner, Lysholm, International Cartilage Repair Society (ICRS), and Cincinnati scores has been reported at 1 and 2 years after AMIC in knees. AMIC is potentially useful to repair defects in hips, but it is unknown whether it relieves symptoms or results in a durable construct. DESCRIPTION OF TECHNIQUE: A surgical hip dislocation is used to access the defect. This is debrided to stable cartilage shoulders, necrotic bone is removed, and the lesion base is drilled. Autogenous bone graft is used for lesions with bony defects to create a level surface. Fibrin gel and a collagen membrane are placed to stabilize the superclot for fibrocartilage formation. METHODS: We treated six patients with AMIC in the hip between 2009 and 2010. We obtained Oxford Hip and UCLA Activity Scores. Repair quality was assessed on 6 month postoperative MRI using the modified magnetic resonance observation of cartilage repair tissue (MOCART) system. Minimum 1-year followup data were available for four patients (range, 1-2.5 years). RESULTS: Postoperative Oxford Hip Scores ranged from 13 to 17, UCLA Activity Scores ranged from 5 to 10, and MOCART scores ranged from 55 to 75. No complications occurred. CONCLUSIONS: We describe AMIC in the hip. Although these patients had pain relief and improved function, long-term followup is necessary to assess the duration of improvement, durability of repair, and potential for arthrosis. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence. PMID- 22773399 TI - [Early diagnosis of infant hearing impairment after introduction of newborn hearing screening (UNHS)]. AB - BACKGROUND: In 2009, the Federal Joint Committee (Gemeinsamer Bundesausschuss, G BA) enacted to introduce the newborn hearing screening (NHS). The records of 11,155 children were analyzed with the aim to obtain data of the age at the time of determined diagnosis of childhood hearing impairment before and after introduction of the NHS. MATERIAL AND METHODS: The records of all children presented at our department between January 1, 2000, and December 31, 2009, based on suspected hearing impairment were evaluated. Additionally the data of 3,325 newborns were analyzed who had been screened between 2003 and 2010. The recorded data included the age at the time of determined diagnosis, the type and grade of hearing impairment of the different age groups, the start and type of rehabilitation, the incidence of consecutive control examinations. RESULTS: For the evaluation interval a total of 1,410 children with permanent hearing impairment could be identified. The mean age at the time of diagnosis was 64 months in 2000 and was reduced to 8.6 months in 2005. Between 2006 and 2009 the babies' mean age was 3.3 months at the time of diagnosis and after introduction of NHS in 2009, the mean age at the time of determined diagnosis was again reduced to 2.4 months. The part of diagnosed sensorineural hearing loss is higher than other hearing disturbances. CONCLUSION: The introduction of NHS verified to improve the early detection of childhood hearing impairment. The early diagnosis allows an early rehabilitation and makes a positive development of the children possible. However, children with permanent hearing impairment require continuous long-term care of competent specialists. PMID- 22773400 TI - [A method for phenotyping specific language impairment (SLI) in children aged 6 8]. AB - BACKGROUND: In recent years possibilities of genotyping have increased rapidly. The more accurate and valid the methods of phenotyping are, the greater is the chance to find genotype-phenotype correlations. For a complex disorder like specific language impairment a dichotomous decision (language impaired - normal developing) is necessary in addition to characterisation of endophenotypes concerning research and clinical practice. MATERIAL AND METHODS: A total of 61 (specific language impaired and normal developing) children aged 6-8 years were examined in a diagnostic study phase I/II. The diagnostic value of a language test battery including 8 subtests derived from German norm-referenced, standardized language tests was evaluated on the basis of different classification analyses. RESULTS: Comparing the means, the subtests of the test battery showed significant differences between the 2 groups. Several analyses of classification validity resulted in acceptable to good (>= 80%) diagnostic accuracy. Best classification rates for sensitivity (92.3%) and specificity (96.0%) were obtained by using logistic regression (method: forward conditional). CONCLUSION: The results empirically support the diagnostic value of the test battery regarding differentiation between children with normal language and those with specific language impairment. However these findings cannot result in recommendations in routine clinical and scientific practice as the study was designed as a Phase I/II diagnostic study. For dichotomous diagnostic decisions a norm-referenced, standardized test should only be used, if there is empirically derived information about its classification validity. PMID- 22773401 TI - [Sialendoscopy--learning curve and nation-wide survey in German ENT-departments]. AB - BACKGROUND: Sialendoscopy is an established, minimal-invasive technique to diagnose and treat obstructive diseases of major salivary glands. Knowledge on learning curve and distribution in Germany is limited. MATERIAL UND METHODS: An 11 item questionnaire on Sialendoscopy was sent to all 159 German ent-hospitals. To determine the learning curve, all patients that underwent sialendoscopy during a 1-year-period after invention of sialendoscopy in our department were prospectively followed and evaluated. RESULTS: Sialendoscopy is currently performed in a minority (24%) of ent-departments in Germany. Denial was justified by technical problems, a lack of cost-benefit and small number of patients in descending order. A significant reduction of intervention time (61.0 +/- 32.7 min to 43.2 +/- 33.6 min, p=0.013) and less frequent aborted operations were noted after comparison of the first vs. the second half amount of interventions as indicators of a learning curve. Complications were not found to be significantly raised in the first half of interventions. CONCLUSION: The fact that sialendoscopy is provided in only a minority of ent-departments will in the future most likely be overcome by technical improvements. A learning curve has to be anticipated. PMID- 22773403 TI - Active management of the third stage of labour. PMID- 22773404 TI - Is surgery a magic bullet against diabetes? PMID- 22773402 TI - Association between three single nucleotide polymorphisms in eotaxin (CCL 11) gene, hexanucleotide repetition upstream, severity and course of coronary atherosclerosis. AB - The impact of three single-nucleotide polymorphisms in eotaxin (SCYA11) gene promoter (-426C>T and -384A>G) and first exon (67G>A) and recently described hexanucleotide (GAAGGA)(n) 10.9 kb upstream on coronary atherosclerosis was investigated. Elective coronary angiography of 1050 consecutive subjects was performed. All patients were genotyped for the three SNPs. In a subset of the first 472 samples, the number of (GAAGGA)(n) repetitions was determined. For further evaluation, short and long variants were distinguished; the borderline corresponded with the median value of all alleles: <=8 repetitions were considered as short sequence, >=9 repetitions as long. Patients with bronchial asthma or insignificant atherosclerosis were excluded; the remaining group of 933 subjects was further investigated. Patients were grouped according to the form of CAD (ACS vs. stable angina) and the number of diseased vessels. The GG variant of 67 G>A polymorphism was associated with acute form of CAD compared to stable angina (p=0.0011, p(corr.)=0.013). The number of (GAAGGA)(n) repetitions in our set of patients ranged from 3 to 12. There were no subjects with 4 or 5 repetitions. The frequency of short repetition alleles increased with the number of affected vessels (1 vs. 3 diseased vessels: p=0.0043, p(corr)=0.034). In our study, the (GAAGGA)(n) hexanucleotide was associated with the severity of CAD. The 67 GG was associated with acute form of CAD. None of the two SNPs in eotaxin promoter had any relation to CAD. The number of (GAAGGA)(n) repetitions can thus be a novel genetic marker of the extent of CAD. PMID- 22773405 TI - Effect of anatomical origin and cell passage number on the stemness and osteogenic differentiation potential of canine adipose-derived stem cells. AB - Mesenchymal stem cells have a great potential for application in cell based therapies, such as tissue engineering. Adipose derived stem cells have shown the capacity to differentiate into several lineages, and have been isolated in many animal species. Dog is a very relevant animal model to study several human diseases and simultaneously an important subject in veterinary medicine. Thus, in this study we assessed the potential of canine adipose tissue derived stem cells (cASCs) to differentiate into the osteogenic and chondrogenic lineages by performing specific histological stainings, and studied the cell passaging effect on the cASCs stemness and osteogenic potential. We also evaluated the effect of the anatomical origin of the adipose tissue, namely from abdominal subcutaneous layer and from greater omentum. The stemness and osteogenic differentiation was followed by real time RT-PCR analysis of typical markers of mesenchymal stem cells (MSCs) and osteoblasts. The results obtained revealed that cASCs exhibit a progressively decreased expression of the MSCs markers along passages and also a decreased osteogenic differentiation potential. In the author's knowledge, this work presents the first data about the MSCs markers profile and osteogenic potential of cASCs along cellular expansion. Moreover, the obtained data showed that the anatomical origin of the adipose tissue has an evident effect in the differentiation potential of the ASCs. Due to the observed resemblances with the human ASCs, we conclude that canine ASCs can be used as a model cells in tissue engineering research envisioning human applications. PMID- 22773407 TI - Noninvasive prediction of intra-amniotic infection and/or inflammation in women with preterm labor: various cytokines in cervicovaginal fluid. AB - OBJECTIVE: To determine the value of cervicovaginal interleukin (IL)-1beta, IL-6, and IL-8 in predicting intra-amniotic infection and/or inflammation (IAI) in women with preterm labor. METHODS: Cervicovaginal fluid samples were collected for IL-1beta, IL-6, and IL-8 measurements immediately before amniocentesis in 85 consecutive women with preterm labor. The IAI was defined as a positive amniotic fluid (AF) culture and/or an elevated AF IL-6 level (>2.6 ng/mL). RESULTS: Receiver-operating characteristic curves demonstrated that cervicovaginal IL-6 and IL-8, but not IL-1beta, predicted IAI. Cervicovaginal IL-6 had a significantly higher area under the curve (AUC) than cervicovaginal IL-8 (P = .009). However, the AUCs for the cervicovaginal IL-6 and AF white blood cell (WBC) were not significantly different. CONCLUSIONS: Among measured cytokines, cervicovaginal IL-6 is the best marker to noninvasively identify IAI in women with preterm labor. Overall, this noninvasive parameter performed as well as AF WBC count for predicting IAI. PMID- 22773406 TI - Epigenetic programming and risk: the birthplace of cardiovascular disease? AB - Epigenetics, through control of gene expression circuitries, plays important roles in various physiological processes such as stem cell differentiation and self renewal. This occurs during embryonic development, in different tissues, and in response to environmental stimuli. The language of epigenetic program is based on specific covalent modifications of DNA and chromatin. Thus, in addition to the individual identity, encoded by sequence of the four bases of the DNA, there is a cell type identity characterized by its positioning in the epigenetic "landscape". Aberrant changes in epigenetic marks induced by environmental cues may contribute to the development of abnormal phenotypes associated with different human diseases such as cancer, neurological disorders and inflammation. Most of the epigenetic studies have focused on embryonic development and cancer biology, while little has been done to explore the role of epigenetic mechanisms in the pathogenesis of cardiovascular disease. This review highlights our current knowledge of epigenetic gene regulation and the evidence that chromatin remodeling and histone modifications play key roles in the pathogenesis of cardiovascular disease through (re)programming of cardiovascular (stem) cells commitment, identity and function. PMID- 22773409 TI - Effects of curcumin on nitrosyl-iron complex-mediated DNA cleavage and cytotoxicity. AB - Combination therapy aims to improve the pharmaceutical efficacy of different drugs, thus lowering the dosages used and reducing the side effects. However, interactions between individual drugs may also occur and lead to uncertain consequences. This study demonstrated that curcumin, a natural phenolic compound found in the rhizomes of turmeric, could either inhibit or enhance DNA cleavage caused by the synthetic nitrosyl-iron complex NC10 ([Fe2(C2H5OS)2(NO)4]). Without UV irradiation, higher concentrations of curcumin protected DNA from being cleaved by NC10. Conversely, in the presence of lower concentrations of curcumin (< 5 uM), cleaved DNA increased by raising curcumin concentrations. After UV irradiation, the DNA protective effect of curcumin decreased while the enhancing DNA cleavage effect of curcumin remained. UV/visible spectroscopy analysis showed that curcumin is associated with the iron of NC10, suggesting the formation of curcumin-Fe complexes. Furthermore, a cytotoxicity assay revealed that cotreatment of NC10 and curcumin had synergetic effects on the growth inhibition of mouse melanoma B16-F10 cells. To our knowledge, this is the first study of the cotreatment of curcumin with inorganic compounds that showed synergistic cytotoxicity. PMID- 22773408 TI - Acidification of the synaptic cleft of cone photoreceptor terminal controls the amount of transmitter release, thereby forming the receptive field surround in the vertebrate retina. AB - In the vertebrate retina, feedback from horizontal cells (HCs) to cone photoreceptors plays a key role in the formation of the center-surround receptive field of retinal cells, which induces contrast enhancement of visual images. The mechanism underlying surround inhibition is not fully understood. In this review, we discuss this issue, focusing on our recent hypothesis that acidification of the synaptic cleft of the cone photoreceptor terminal causes this inhibition by modulating the Ca channel of the terminals. We present evidence that the acidification is caused by proton excretion from HCs by a vacuolar type H(+) pump. Recent publications supporting or opposing our hypothesis are discussed. PMID- 22773411 TI - Suicide is preventable, sometimes. AB - OBJECTIVE: The objective was to examine the assumption that suicide is inevitably preventable. CONCLUSIONS: Suicide may not always be avoidable. This does not mean that every effort should not be made to prevent it or vigorously treat illnesses that are often contributory. The assumption, however, may give rise to undue optimism, and unjustified blame when suicides do occur. PMID- 22773410 TI - Deoxyschizandrin isolated from the fruits of Schisandra chinensis ameliorates Abeta1-42-induced memory impairment in mice. AB - In the present study, we examined the effects of deoxyschisandrin (DS) from Schisandra chinensis on the amyloid-beta1-42 (Abeta1-42)-induced memory impairment in mice and investigated the possible antioxidative mechanism. Mice were given an intracerebroventricular (i. c. v.) injection with the aggregated Abeta1-42 and then treated with DS (4, 12, and 36 mg/kg body weight) or donepezil (DPZ), a positive control drug (0.65 mg/kg), by intragastric infusion for 14 days. Non-cognitive disturbances and cognitive performance were evaluated by the locomotor activity, Y-maze, and water maze tests. Antioxidative enzyme activities including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and levels of malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG) within the cerebral cortex and hippocampus of mice were measured to investigate the mechanism. Our results showed that DS significantly improved Abeta1-42-induced short-term and spatial memory impairments in the Y-maze and water maze tests. Furthermore, in the cerebral cortex and hippocampus of mice, the reduced activities of SOD and GSH-px, the GSH level, and the GSH/GSSG ratio were increased, and increased levels of MDA and GSSG were reduced following treatment with DS, although the improvement of GSH and the reduction of GSSG levels were not marked. These results suggest that DS is a potential cognitive enhancer in Alzheimer's disease through its antioxidative action. PMID- 22773412 TI - E-CYMHS: an expansion of a child and youth telepsychiatry model in Queensland. AB - OBJECTIVES: The purpose of this study was to describe the evolution of the E Child and Youth Mental Health Service (E-CYMHS), which supports regional and rural mental health services by providing access to consultant child and adolescent psychiatrists to isolated staff in regional areas, where access to specialist psychiatric services is limited. CONCLUSIONS: E-CYMHS provides a level of parity in mental health care between metropolitan, regional and remote services through the provision of regular videoconferencing services with child and adolescent psychiatrists and senior allied health clinicians. The three key features which underpin the success of the service are: 1. A central co-ordinator of services; 2. Provision of support outside regular videoconference times; and 3. Routine outreach visits that foster community capacity-building. E-CYMHS has been well received by the regional mental health services it supports, and the total provision of services has more than doubled over the last three years. It is anticipated that as telepsychiatry is increasingly viewed as a credible alternative to traditional means of patient care, this trend is likely to continue. PMID- 22773413 TI - Patterns of hypnotic medication use for sleep disturbance amongst hospital inpatients. AB - OBJECTIVE: The objective of this article is to examine patterns of temazepam prescribing amongst inpatients at a Sydney teaching hospital. METHOD: The study involved a retrospective file audit of 98.8% (n=410) of patients discharged from psychiatry, medical, surgical and obstetric and gynaecology wards of Nepean Hospital during a one-week period. Data was collected on patient demographics, temazepam and other sedative-hypnotic use, falls risk and analgesia use. RESULTS: Sixteen per cent (n=64) of patients were prescribed temazepam during their stay. All patients from the psychiatry wards had been prescribed temazepam. Fifteen per cent (n=6) of falls risk patients had been prescribed temazepam. Temazepam prescription was associated with an increased length of stay, psychiatry and surgical wards, and higher use of analgesia. CONCLUSIONS: Temazepam continues to be a frequently prescribed medication in the acute psychiatry setting. Its frequent prescription to patients in surgical wards and to those prescribed analgesic agents indicates that it still has a role in settling patients to sleep in the hospital setting. PMID- 22773415 TI - [Hollow organ injury and multiple trauma: treatment, course and outcome - an organ-specific evaluation of 1127 patients from the trauma registry of the DGU]. AB - BACKGROUND: The relevance of hollow organ trauma in severely injured patients within a large collective has not been thoroughly reviewed as yet. This study aimed at assessing the prevalence of hollow organ trauma in relation to the outcome and the currently established method of treatment. PATIENTS AND METHODS: Altogether data of all patients of the Trauma Register of the German Society of Trauma Surgery (DGU) (1993 - 2009) were interpreted retrospectively. All patients with an "Injury Severity Score" (ISS) >= 16, direct admission to a trauma centre and an age of >= 16 years were included. All patients with abdominal trauma (AISabdomen >= 2) were compared with patients with hollow organ trauma (AIShollow organ >= 2). The following organs were attributed to the hollow organs: stomach, small intestine (duodenum, jejunum / ileum), colon, gall bladder and urinary bladder. RESULTS: From 9268 patients with abdominal injuries 1127 (12.2 %) additionally showed a hollow organ injury (AISabdomen >= 2, AIShollow organ 2 - 5) and were analysed in dependence on the classification of the "American Association for the Surgery of Trauma" (AAST) organ severity score. AAST-hollow organ: II degrees : 4.6 %, III degrees : 5.3 %, IV degrees : 2.1 %, V degrees : 0.2 %. Patients with leading hollow organ injury (grades IV and V) thereby showed a significant increase of lethality (IV degrees : 32.7 % and V degrees : 31.3 %). With an increasing grade of hollow organ injury, however, the ISS increased as well. Lethality was not increased over the expected lethality rate (RISC score) due to the additional hollow organ injury though. CONCLUSION: The results presented here show the prevalence and the outcome of hollow organ injury in a large collective within the Trauma Register of the DGU for the first time. PMID- 22773416 TI - Preliminary validation of the Nepean Dysphoria Scale. AB - OBJECTIVE: To present the psychometric properties of the Nepean Dysphoria Scale (NDS), the first instrument developed to measure the severity of dysphoria. METHOD: The NDS was administered to 134 university students and its characteristics were examined. The structure of the scale was investigated using exploratory factor analysis. Convergent and divergent validity were examined by investigating the associations between the NDS and its subscales with other conceptually similar (Beck Depression Inventory II, Dysfunctional Attitude Scale Form A and Toronto Alexithymia Scale) and conceptually distinct (Anxiety Sensitivity Index) instruments. RESULTS: The 24-item NDS demonstrated excellent internal consistency. A four-factor solution was derived, with factors pertaining to irritability, discontent, surrender and interpersonal resentment. There were medium to strong correlations between the NDS and its subscales and depressive symptoms as measured by the Beck Depression Inventory II. The NDS and its subscales showed weaker, but still significant, correlations with Dysfunctional Attitude Scale-Form A, Toronto Alexithymia Scale and Anxiety Sensitivity Index. CONCLUSIONS: The study suggests that the NDS has good psychometric properties. Further research would more firmly establish the NDS as a valid measure of the complex emotional state of dysphoria. PMID- 22773417 TI - Looking like a criminal: stereotypical black facial features promote face source memory error. AB - The present studies tested whether African American face type (stereotypical or nonstereotypical) facilitated stereotype-consistent categorization, and whether that categorization influenced memory accuracy and errors. Previous studies have shown that stereotypically Black features are associated with crime and violence (e.g., Blair, Judd, & Chapleau Psychological Science 15:674-679, 2004; Blair, Judd, & Fallman Journal of Personality and Social Psychology 87:763-778, 2004; Blair, Judd, Sadler, & Jenkins Journal of Personality and Social Psychology 83:5 252002); here, we extended this finding to investigate whether there is a bias toward remembering and recategorizing stereotypical faces as criminals. Using category labels, consistent (or inconsistent) with race-based expectations, we tested whether face recognition and recategorization were driven by the similarity between a target's facial features and a stereotyped category (i.e., stereotypical Black faces associated with crime/violence). The results revealed that stereotypical faces were associated more often with a stereotype-consistent label (Study 1), were remembered and correctly recategorized as criminals (Studies 2-4), and were miscategorized as criminals when memory failed. These effects occurred regardless of race or gender. Together, these findings suggest that face types have strong category associations that can promote stereotype motivated recognition errors. Implications for eyewitness accuracy are discussed. PMID- 22773414 TI - Event-related induced frontal alpha as a marker of lateral prefrontal cortex activation during cognitive reappraisal. AB - Electrocortical activity, typically used to track the effects of cognitive reappraisal on the processing of emotional stimuli, has not been used to index the prefrontal-cortex-mediated regulatory mechanisms responsible for these effects. In the present study, we examined the novel possibility that induced frontal alpha (i.e., 8-13 Hz), shown to reflect the inhibition and disengagement of task-relevant cortical regions, may be quantified to explore cortical activation that is specifically enhanced during cognitive reappraisal. For this purpose, 44 participants viewed unpleasant and neutral pictures followed by auditory instructions to either continue viewing the picture or reduce their emotional response to the picture by making the picture seem less emotional (i.e., cognitive reappraisal). In line with previous work, unpleasant pictures elicited a larger late positive potential (LPP) than did neutral pictures. Also corroborating previous work, the mid-latency LPP was reduced when pictures were cognitively reappraised. However, the present study showed for the first time that whereas unpleasant pictures elicited higher frontal alpha power bilaterally than did the neutral pictures, frontal alpha power was reduced (indicative of more activation and cognitive control) during cognitive reappraisal of both picture types over the left hemisphere. Taken together, the LPP and event-related induced frontal-alpha findings contribute unique information about the distinct neural substrates and cognitive processes underlying reappraisal. PMID- 22773418 TI - Launching "On film and digital media". PMID- 22773419 TI - Coming to a theater near you. PMID- 22773420 TI - "Tis a far better thing": digital technology in gerontological education. PMID- 22773422 TI - Created equal? The many facets of cell reprogramming. PMID- 22773423 TI - Mysteries in the local control of blood flow: a physiological "whodunit" involving red cell release of ATP? PMID- 22773424 TI - Mutations in the sensitive giant titin result in a broken heart. PMID- 22773425 TI - Mature cardiomyocytes recall their progenitor experience via polycomb repressive complex 2. PMID- 22773429 TI - Antigen-dependent and antigen-independent pathways modulate CD4+CD28null T-cells during atherosclerosis. PMID- 22773427 TI - Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. AB - Atherosclerosis is classed as a disease of aging, such that increasing age is an independent risk factor for the development of atherosclerosis. Atherosclerosis is also associated with premature biological aging, as atherosclerotic plaques show evidence of cellular senescence characterized by reduced cell proliferation, irreversible growth arrest and apoptosis, elevated DNA damage, epigenetic modifications, and telomere shortening and dysfunction. Not only is cellular senescence associated with atherosclerosis, there is growing evidence that cellular senescence promotes atherosclerosis. This review examines the pathology of normal vascular aging, the evidence for cellular senescence in atherosclerosis, the mechanisms underlying cellular senescence including reactive oxygen species, replication exhaustion and DNA damage, the functional consequences of vascular cell senescence, and the possibility that preventing accelerated cellular senescence is a therapeutic target in atherosclerosis. PMID- 22773426 TI - Molecular imaging of atherosclerosis for improving diagnostic and therapeutic development. AB - Despite recent progress, cardiovascular and allied metabolic disorders remain a worldwide health challenge. We must identify new targets for therapy, develop new agents for clinical use, and deploy them in a clinically effective and cost effective manner. Molecular imaging of atherosclerotic lesions has become a major experimental tool in the last decade, notably by providing a direct gateway to the processes involved in atherogenesis and its complications. This review summarizes the current status of molecular imaging approaches that target the key processes implicated in plaque formation, development, and disruption and highlights how the refinement and application of such tools might aid the development and evaluation of novel therapeutics. PMID- 22773430 TI - Bioequivalence of acenocoumarol in chilean volunteers: an open, randomized, double-blind, single-dose, 2-period, and 2-sequence crossover study for 2 oral formulations. AB - The aim of this study was to compare the bioavailability of an oral formulation of the coumarin derivative-vitamine K antagonist acenocoumarol (AcebronTM 4 mg, Test) with the reference formulation (Neo-SintromTM 4 mg). We performed a single dose, double-blind, fasting, 2-period, 2-sequence, crossover study design. Plasma concentrations of acenocoumarol were determined using a validated UPLC-MS/MS method. 24 healthy Chilean volunteers (11 male, 13 female) were enrolled and all of them completed the study. Adverse events were monitored throughout the study. The values of the pharmacokinetic parameters were (mean +/- SD): AUC0-24 =1 364.38+/-499.26 ngxh/mL for the test and 1 328.39+/-429.20 ngxh/mL for the reference; AUC0-infinity =1 786.00+/-732.85 ngxh/mL for the test and 1 706.71+/ 599.66 ngxh/mL for the reference; Cmax =180.69+/-35.11 ng/mL with a Tmax of 1.83+/-0.95 h for the test and 186.97+/-38.21 ng/mL with a Tmax of 2.19+/-0.83 h for the reference. Regarding half life measurements, the mean +/- SD of t1/2 were 11.84+/-4.54 h for the test and 11.08+/-3.28 h for the reference. The 90% confidence intervals for the test/reference ratio using logarithmic transformed data were 97.89-100.87%, 98.62-101.99% and 98.64-102.38% for Cmax, AUC0-t(24) and AUC0-infinity. There were no significant differences in pharmacokinetic parameters between groups.The results obtained in this study lead us to conclude, based on FDA criteria, that the test acenocoumarol formulation (AcebronTM, 4 mg tablets) is bioequivalent to the reference product (Neo-SintromTM, 4 mg tablets). PMID- 22773431 TI - Pain amelioration in patients with neuropathic pain: an emerging role of lacosamide besides its role as an anti epileptic agent. PMID- 22773433 TI - Estimating discrimination performance in two-alternative forced choice tasks: routines for MATLAB and R. AB - Ulrich and Vorberg (Attention, Perception, & Psychophysics 71: 1219-1227, 2009) introduced a novel approach for estimating discrimination performance in two alternative forced choice (2AFC) tasks. This approach avoids pitfalls that are inherent when the order of the standard and the comparison is neglected in estimating the difference limen (DL), as in traditional approaches. The present article provides MATLAB and R routines that implement this novel procedure for estimating DLs. These routines also allow to account for processing failures such as lapses or finger errors and can be applied to experimental designs in which the standard and comparison differ only along the task-relevant dimension, as well as to designs in which the stimuli differ in more than one dimension. In addition, Monte Carlo simulations were conducted to check the quality of our routines. PMID- 22773432 TI - Efficacy and effect on plasma B-type natriuretic peptide concentration of losartan-hydrochlorothiazide for hypertension uncontrolled by losartan-based therapy: subanalysis of a Multicentre Prospective Observational Study. AB - Many patients with hypertension have difficulty achieving their target blood pressure (BP). Therefore combination therapy, for example with an angiotensin II receptor blocker (ARB) and a diuretic, may be recommended. We previously evaluated the efficacy and safety of losartan (LOS) 50 mg - hydrochlorothiazide (HCTZ) 12.5 mg, as well as its effect on the plasma concentration of B-type natriuretic peptide (BNP, a prognostic marker for cardiovascular events), in patients with hypertension uncontrolled by >=3 months of ARB-based therapy. The present subanalysis used data from patients who received LOS-based therapy before switching to LOS-HCTZ. Efficacy, safety, and changes in blood biochemical variables including BNP were evaluated. After excluding 4 patients with protocol violations, data from 35 patients (aged 36-79 years, mean 63 years; 66% male) were used in the safety analysis. The efficacy analysis used data from the 30 patients who were followed up for 12 months. Systolic/diastolic BP decreased from 156+/-12/87+/-11 mmHg at baseline to 125+/-11/73+/-10 mmHg at 12 months (p<0.001). After 12 months, half of the patients achieved their target BP as defined by the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2004. In 12 patients with baseline plasma BNP concentration >=20 pg/mL, BNP decreased from 78.3+/-18.8 pg/mL to 57.3+/-17.7 pg/mL (p<0.01). 3 patients experienced adverse events, one of which was cardiovascular. LOS-HCTZ is efficacious, has a good safety profile, and decreases plasma BNP concentration. PMID- 22773434 TI - Methods for comparing scanpaths and saliency maps: strengths and weaknesses. AB - In this article, we are interested in the computational modeling of visual attention. We report methods commonly used to assess the performance of these kinds of models. We survey the strengths and weaknesses of common assessment methods based on diachronic eye-tracking data. We then illustrate the use of some methods to benchmark computational models of visual attention. PMID- 22773435 TI - Protective effect of Calligonum comosum on haloperidol-induced oxidative stress in rat. AB - The aqueous and methanolic extracts of Calligonum comosum were investigated for their antioxidant and dopaminergic effects on haloperidol (HL)-induced neuro- and hepatotoxicities in male albino rat model. The total phenolics, flavonoid content and free radical-scavenging activity of the extracts were determined. The results showed that the antioxidant activity of the methanolic extract was higher than the aqueous one. HL significantly reduced GSH and increased MDA in brain and liver tissues. These values were nearly normalized, in the examined tissues, on concomitant administration of C. comosum methanolic extract with HL. Superoxide dismutase activity in the examined tissues was significantly decreased by HL administration that was normalized by the coadministration of the methanolic extract and, to a less extent, the water extract. Determination of the brain neurotransmitter contents revealed a marked decrease in norepinephrine, dopamine and serotonin, which were restored to near control values by concomitant administration of both C. comosum extracts with HL. The results of this study showed that C. comosum methanolic and aqueous extracts ameliorated HL-induced neuro- and hepatotoxicities in rats. PMID- 22773436 TI - Apoptosis and lipid peroxidation in ochratoxin A- and citrinin-induced nephrotoxicity in rabbits. AB - Ochratoxin A (OTA) and citrinin (CIT) are nephrotoxic mycotoxins produced mainly by fungal species Aspergillus ochraceus and Penicillium citrinum, respectively, which have been found to occur together in various food and feed commodities. In the present study, both OTA and CIT were evaluated for their potential to induce oxidative damage by determining lipid peroxidation (LPO) through malondialdehyde (MDA) assay and apoptosis by flow cytometry, gel electrophoresis and renal ultrastructural morphology in rabbits fed with diets containing OTA (0.75 mg/kg feed), CIT (15 mg/kg feed) and OTA + CIT (0.75 and 15 mg/kg feed, respectively) up to 60 days. The concentration of MDA was found significantly higher in OTA and combination-treated groups. OTA and combination-treated groups revealed more apoptotic cells in flow cytometry when compared with the CIT-treated group. Characteristic DNA fragmentation, as evidenced by ladder pattern in electrophoresis appeared in the toxin-treated groups. Ultrastructurally, interstitial cells showed nuclear fragmentation and cytoplasmic blebbing in OTA- and CIT-treated groups; whereas, proximal convoluted tubular epithelial cells, besides interstitial cells, showed nuclear fragmentation in the combined treatment group. The results suggested that low concentrations of OTA and CIT either alone or in combination induced apoptosis in a time-dependent manner and LPO in the rabbit kidney, which appeared to play a major role in the pathogenesis of nephrotoxicity. Furthermore, the interaction of these two nephrotoxic mycotoxins was found to be additive. PMID- 22773437 TI - Mortality and antioxidant responses in the planarian (Dugesia japonica) after exposure to copper. AB - The planarians (Dugesia japonica) are distributed widely in China, Japan, Korea, and southern Siberia. In this study, the acute toxicity of copper on D. japonica was evaluated using mortality and the activity of the enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and reactive oxygen species (ROS) as endpoints. Acute toxicity tests were conducted according to the American Society for Testing and Materials guidelines. The 24-, 48-, 72-, and 96-h median lethal concentration that killed 50% of individuals (LC50) were calculated as 8.70, 6.31, 4.48, and 4.23 mg Cu2+/L, respectively, based on measured copper concentrations. When compared with different phyla or classes of freshwater animals, the rank of D. japonica in species sensitivity was in the range of 25-26 for 96-h LC50. The antioxidant enzymes SOD and CAT were determined in D. japonica exposed to two copper concentrations (50 and 100 MUg Cu2+/L) with a short-term exposure (15 days). They all attained peak value and then reduced during the experimental period. The GPx activities were activated only for 100 MUg/L treatments at days 3 and 6 and then renewed to the original level. Meanwhile, copper significantly increased the levels of ROS in D. japonica. Our study suggests that the adult D. japonica was less sensitive to copper than most other aquatic species. Copper may induce oxidative stress and interfere with the antioxidant defense system of the D. japonica, including SOD and CAT. GPx might be an insusceptible antioxidant enzyme in the metabolic detoxification processes in adult D. japonica. PMID- 22773438 TI - Effects of (99m)Tc sestamibi on antioxidant defense system and lipid peroxidation in the heart of Sprague Dawley rats. AB - Nuclear medicine has been using radiopharmaceuticals for the diagnostic and therapeutic purposes of many diseases. Technetium-(99m) methoxyisobutylisonitrile ((99m)Tc sestamibi) is a lypophilic complex that has a positive-loaded isonitril group. Aim of the study is to investigate whether (99m)Tc sestamibi, which is one of the mostly used radiopharmaceuticals in nuclear medicine field, causes oxidative damage or not in rats' heart after an injection. A total of 16 male Sprague Dawley rats were randomly divided into two groups: group I: (99m)Tc sestamibi group, (99m)Tc sestamibi administered intravenously with the dose of 25MBq; group II: control group, one dose of isotonic sodium chloride was administered intravenous with the same volume as (99m)Tc sestamibi group. Malondialdehyde (MDA) and total oxidant status (TOS) were used as markers of oxidative stress-induced heart impairment. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant status (TAS) activities were studied to evaluate the changes in the antioxidant status. In the (99m)Tc sestamibi group (group I), animals treated with (99m)Tc sestamibi produced a significant decrease in the activities of antioxidant enzymes (SOD and CAT), while MDA level increased when compared with control group (group II) in myocardial tissue (p < 0.05). On the other hand, the GSH-Px activities were significantly increased in the (99m)Tc sestamibi-treated rats compared with the untreated rats (p < 0.05). There was no significant difference in the TAS and TOS levels of plasma. PMID- 22773439 TI - Management of arteriovenous malformations related to Spetzler-Martin grading system. AB - Advanced technology and improved understanding of the natural history of arteriovenous malformations (AVMs) led to the reconsideration of the management of these lesions, which once comprised purely microsurgical removal. A multidisciplinary approach for both the evaluation and treatment of AVMs has gained acceptance within the past few decades. Treatment options for AVMs include surgical resection, embolization, or stereotactic radiosurgery, or any combination of these procedures. The risk of a chosen management strategy must include the sum of the risk of all the interventions applied to a given lesion, and this should be compared with the natural history of a given lesion in a particular clinical setting. Among all components of the multimodality treatment, however, microsurgical removal remains the definitive form of treatment. PMID- 22773440 TI - Frameless navigated biopsy with the BrainLAB(r) VarioGuide system: a technical note. AB - OBJECTIVE: Implementation of a new neuronavigation system in the department included the opportunity to change the brain biopsy procedures from a frame-based system to a frameless system--the BrainLAB(r) VarioGuide. We report our first 20 consecutive procedures within 2 years, analyzing the effectiveness of this new tool. PATIENTS, MATERIALS, AND METHODS: 15 men and 5 women with various intracerebral lesions were biopsied. Their average age was 62 years (range, 41-83 years). Preoperative planning was performed using computed tomography (CT) or magnetic resonance imaging (MRI) data provided by a radiological picture archiving and communication system (PACS) sent to the planning station. Planning was based on either MRI or CT in 14 and 4 cases, respectively, and a combination of both in 2 cases. RESULTS: The lesions had a mean maximal diameter of 42.97 mm (range, 5.8-109.8 mm). 19 lesions were supratentorial, 1 of those intraventricular, and 1 lesion was infratentorial, within the cerebellar peduncle and brainstem. During surgery, the samples were sent to neuropathological examination, and the procedure was completed after confirmation that pathological tissue was obtained. In 18 of 20 cases, definitive pathological tissue was harvested. Histopathology confirmed 8 glioblastomas, 1 oligoastrocytoma, 4 anaplastic astrocytomas, 1 astrocytoma, and 2 primary central nervous system lymphomas, as well as 1 encephalitis and 1 necrotic tissue of unknown origin. In 3 cases, including the case of necrotic tissue, there was no final diagnosis possible. Referencing the BrainLAB(r) navigation system and software-wizard guided sterile adjustment of the VarioGuide arm over the entry point took 5 to 10 minutes. The mean operation time was 49 minutes (range, 24-69 minutes) including the time until first neuropathological examination was completed. No adverse events occurred during or after the operation. PMID- 22773443 TI - More than 30 NHS organisations end 2011-12 in debt totalling L356m. PMID- 22773444 TI - Reorganisation of public health in England is "a terrible mess," conference hears. PMID- 22773442 TI - Smooth muscle cell-specific runx2 deficiency inhibits vascular calcification. AB - RATIONALE: Vascular calcification is a hallmark of atherosclerosis, a major cause of morbidity and mortality in the United States. We have previously reported that the osteogenic transcription factor Runx2 is an essential and sufficient regulator of calcification of vascular smooth muscle cells (VSMC) in vitro. OBJECTIVE: To determine the contribution of osteogenic differentiation of VSMC to the pathogenesis of vascular calcification and the function of VSMC-derived Runx2 in regulating calcification in vivo. METHODS AND RESULTS: SMC-specific Runx2 deficient mice, generated by breeding SM22alpha-Cre mice with the Runx2 exon 8 floxed mice, exhibited normal aortic gross anatomy and expression levels of SMC specific marker genes. Runx2 deficiency did not affect basal SMC markers, but inhibited oxidative stress-reduced expression of SMC markers. High-fat-diet induced vascular calcification in vivo was markedly inhibited in the Runx2 deficient mice in comparison with their control littermates. Runx2 deficiency inhibited the expression of receptor activator of nuclear factor kappaB ligand, which was accompanied by decreased macrophage infiltration and formation of osteoclast-like cells in the calcified lesions. Coculture of VSMC with bone marrow-derived macrophages demonstrated that the Runx2-deficient VSMC failed to promote differentiation of macrophages into osteoclast-like cells. CONCLUSIONS: These data have determined the importance of osteogenic differentiation of VSMC in the pathogenesis of vascular calcification in mice and defined the functional role of SMC-derived Runx2 in regulating vascular calcification and promoting infiltration of macrophages into the calcified lesion to form osteoclast-like cells. Our studies suggest that the development of vascular calcification is coupled with the formation of osteoclast-like cells, paralleling the bone remodeling process. PMID- 22773445 TI - London trust lost track of over 1000 patients referred for suspected cancer. PMID- 22773446 TI - Health department refuses plea for private PIP implants to be replaced on NHS. PMID- 22773447 TI - Two doctors are referred to the GMC for taking industrial action. PMID- 22773449 TI - Proteoglycans from Boswellia serrata Roxb. and B. carteri Birdw. and identification of a proteolytic plant basic secretory protein. AB - Water-soluble high molecular weight compounds were isolated in yields of 21-22% from the oleogum of Boswellia serrata and B. carteri. Using anion exchange chromatography and gel permeation chromatography, different proteoglycans were purified and characterized, leading to four principally different groups: (i) Hyp /Ser-rich extensins with O-glycosidic attached arabinan side chains; (ii) Modified extensins, with arabinogalactosylated side chains containing GlA and 4-O Me-GlcA; (iii) Glycoproteins with N-glycosidic side chains containing higher amounts of Fuc, Man and GluNH(2,) featuring a 200 kD metalloproteinase that has been de novo sequenced and is described for the first time; (iv) Type II arabinogalactans-proteins. Significant differences between the gums from the two species were observed in the protein content (6% vs 22%), offering the possibility of a quick differentiation of gums from both species for analytical quality control. The data also offer an insight into the plant response towards wound-closing by the formation of extensin and AGP-containing gum. PMID- 22773450 TI - The biology of caring: researching the healing effects of stress response regulation through relational engagement. AB - Caring, a core tenet of nursing practice, grew out of a holistic approach. Nurse theorists often note the establishment of a therapeutic relationship as the beginning point of caring, with subsequent nursing interventions reliant upon this relationship for effectiveness. Relational exchange serves as a source of either stress or healing between participants, and rarely is its impact neutral. Relational stress, in fact, has become a primary contributor to many disease processes in terms of promotion and progression and perhaps even initiation. Patient-provider relationships have a long history in medical and nursing literature as critical to providing effective interventions, but our understanding of relational dynamics between patients and providers remains fairly superficial. This theoretical article adapts a previously described biobehavioral model to illustrate the nature and centrality of caring relationships in nursing practice. The dynamic process of face-to-face engagement is deconstructed from a psychobiological standpoint in order to understand the physiological, emotional, cognitive, and behavioral impacts of relational interaction. This understanding is then applied to the patient-provider relationship. Finally, the utility of biomarkers of stress, positive emotion and resonance, and of disease is discussed relative to the patient-provider relationship. Methodological and interpretive challenges inherent in this line of research, along with suggestions to address such challenges, are also presented. PMID- 22773451 TI - Interpersonal touch: physiological effects in critical care. AB - INTRODUCTION: Nurses use several forms of touch in patient encounters. Interpersonal touch elicits specific physiological and psychological responses, including neuroendocrine effects and reduction of stress. Critical illness is a state of excessive physiological and psychological stress. AIMS: To critically review evidence on the effect of touch on physiological outcomes in critically ill individuals. Results of intervention studies in adult critical care settings were reviewed along with supportive evidence from studies in other populations. METHODS: Critical literature review based on studies published in MEDLINE, PubMed, Cinahl, Embase, and Cochrane databases. RESULTS: Eleven studies were reviewed. Significant effects of interpersonal touch included lower systolic and diastolic blood pressure and respiratory rate, improved sleep, and decreased pain. Almost no results were replicated owing to discrepancies among studies. Although the effect of touch on cardiovascular autonomic status appears considerable, several confounders must be considered. In noncritically ill populations, replicable findings included increased urinary dopamine and serotonin, natural killer cytotoxic activity, and salivary chromogranin. Effects on plasma cortisol and immune cells were variable. Effects appear to vary according to amount of pressure, body site, duration, and timing: Moderate pressure touch may elicit a parasympathetic response in contrast to light touch, which may elicit a sympathetic response. Moreover, touch effects may be mediated by the density of autonomic innervation received by the body areas involved and repetition of sessions. CONCLUSION: The physiological pathway mediating the effects of touch is unclear. Although no concrete conclusions can be drawn, research evidence suggests that touch interventions may benefit critically ill individuals. PMID- 22773448 TI - Role of heparan sulfate in sexually transmitted infections. AB - Cell surface heparan sulfate (HS), a polysaccharide composed of alternating uronic acid and glucosamine residues, represents a common link that many sexually transmitted infections (STIs) require for infection. Variable modifications within the monomeric units of HS chains together with their unique structural conformations generate heterogeneity, which expands the ability of HS to bind a diverse array of host and microbial proteins. Recent advances made in the field of glycobiology have critically enhanced our understanding of HS and its interactions with microbes and their significance in important human diseases. The role of HS has been elaborated for several STIs to include those caused by herpes simplex virus, human immunodeficiency virus, human papillomavirus, and Chlamydia. In addition, gonorrhea, syphilis, and yeast infections are also dependent on the presence of HS on human target cells. Critical steps such as pathogen adhesion or binding to host cells followed by internalization to enhance intracellular survival and possible spread to other cells are mediated by HS. In addition, HS guided cell signaling plays a role in the development of angiogenesis and inflammation associated with many STIs. Past and ongoing investigations are providing new push for the development of HS-mimetics and analogs as novel prevention strategies against many different STIs. This review article summarizes the significance of HS in STIs and describes how emerging new products that target HS can be used to control the spread of STIs. PMID- 22773452 TI - A rare cause of CSF shunt "failure" in a patient with NPH. PMID- 22773454 TI - Hyperbilirubinemia, augmentation of endothelial function, and decrease in oxidative stress in Gilbert syndrome. AB - BACKGROUND: Patients with Gilbert syndrome have mild unconjugated hyperbilirubinemia. It has been shown that bilirubin is an endogenous antioxidant. We evaluated the role of oxidative stress in endothelial function in patients with Gilbert syndrome under normal conditions without cardiovascular risk factors. METHODS AND RESULTS: A total of 108 young men with Gilbert syndrome without cardiovascular risk factors and 108 age-matched healthy men (normal controls) were enrolled in this study. Serum concentrations of bilirubin were higher in patients with Gilbert syndrome than in control subjects (29.2+/-11.6 versus 9.4+/-2.7 MUmol/L; P<0.001). Serum concentrations of malondialdehyde modified low-density lipoprotein and urinary excretion of 8-hydroxy-2' deoxyguanosine (8-OHdG), as indices of oxidative stress, were lower in patients with Gilbert syndrome than in control subjects (61.8+/-24.5 versus 72.5+/-21.8 U/L, P=0.034; 7.8+/-2.4 versus 10.4+/-3.2 ng/mg creatinine, P=0.001, respectively). Flow-mediated vasodilation was greater in patients with Gilbert syndrome than in normal control subjects (7.2+/-2.2% versus 5.9+/-1.7%; P<0.001). Vascular responses to nitroglycerine were not significantly different between the 2 groups. Flow-mediated vasodilation correlated with serum concentration of bilirubin (r=0.44, P<0.001), malondialdehyde-modified low-density lipoprotein (r= 0.25, P=0.01), and urinary excretion of 8-OHdG (r=-0.27, P=0.004) in patients with Gilbert syndrome but not in control subjects. In addition, serum concentration of bilirubin correlated with malondialdehyde-modified low-density lipoprotein (r=-0.20, P=0.04) and 8-OHdG (r=-0.21, P=0.02) in patients with Gilbert syndrome but not in control subjects. CONCLUSIONS: Patients with Gilbert syndrome had low levels of oxidative stress associated with hyperbilirubinemia and enhancement of endothelium-dependent vasodilation. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp. Unique identifier: UMIN000003409. PMID- 22773455 TI - Postischemic dementia with Alzheimer phenotype: selectively vulnerable versus resistant areas of the brain and neurodegeneration versus beta-amyloid peptide. AB - The road to clarity for postischemic dementia mechanisms has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution. Importantly, brain ischemia is a leading cause of death and cognitive impairment worldwide. However, the mechanisms of progressive cognitive decline following brain ischemia are not yet certain. Data from animal models and clinical pioneering studies of brain ischemia have demonstrated an increase in expression and processing of amyloid precursor protein to a neurotoxin oligomeric beta-amyloid peptide. Functional and memory brain restoration after ischemic brain injury is delayed and incomplete due to a lesion related increase in the amount of the neurotoxin amyloid protein. Moreover, ischemic injury is strongly accelerated by aging, too. In this review, we will present our current thinking about biogenesis of amyloid from the amyloid precursor protein in ischemic brain injury, and how this factor presents etiological, therapeutic and diagnostic targets that are now under consideration. Progressive injury of the ischemic brain parenchyma may be caused not only by degeneration of selectively vulnerable neurons destroyed during ischemia but also by acute and chronic damage of resistant areas of the brain and progressive damage in the blood-brain barrier. We propose that in postischemic dementia an initial ischemic injury precedes the cerebrovascular and brain parenchyma accumulation of Alzheimer disease related neurotoxin beta-amyloid peptide, which in turn amplifies the neurovascular dysfunction triggering focal ischemic episodes as a vicious cycle preceding final neurodegenerative pathology. Persistent ischemic blood-brain barrier insufficiency with accumulation of neurotoxin beta-amyloid protein in the brain tissue, especially in extracellular perivascular space and blood-brain barrier microvessels, may gradually, over a lifetime, progress to brain atrophy and to full-blown ischemic dementia with Alzheimer phenotype. PMID- 22773456 TI - Clinical aspects of molecular biology of pituitary adenomas. AB - Pituitary adenomas are primary, benign CNS tumors. Sporadically, they metastasize or become malignant. However, they can infiltrate adjacent structures even if they are benign and without hormonal activity. Moreover, by compressing adjacent tissues they cause their gradual degradation and, as a result, irreversible CNS damage. Pure endoscopic transnasal transsphenoidal approach enables minimally invasive resection of the aforementioned tumors. In most cases, standard total resection is sufficient but in some cases tumors could be recurrent. There are still unknown risk factors leading to recurrence and subsequent progression of these tumors. This is the reason why pituitary adenomas are a serious clinical and social problem in spite of their benign histology. Continuous development of immunohistochemical and proteomic examinations and application of advanced methods of functional genomics allow for better understanding of biology and pathogenesis of these tumors. In the paper authors discuss molecular etiopathogenesis of pituitary adenomas. PMID- 22773457 TI - Ultrastructural pathology of endothelial tight junctions in human brain oedema. AB - Cortical biopsies of patients with the diagnosis of complicated brain trauma, congenital hydrocephalus, brain vascular anomaly, and brain tumour are studied with the electron microscope using cortical biopsies of different cortical brain regions to analyze the alterations of endothelial junctions, and their participation in the pathogenesis of human brain oedema. In moderate oedema, most endothelial tight junctions are structurally closed and intact, while in some cases of severe oedema, the opening of tight endothelial junctions is observed. In very severe brain oedema, a considerable enlargement of interjunctional pockets of extracellular space is also seen suggesting that in highly increased cerebrovascular permeability, the endothelial junctions are open in their entire extent, and that an intercellular or paracellular route through interendothelial clefts for transferring haematogenous oedema fluid from blood to the capillary basement membrane and the brain parenchyma is formed, contributing to the formation of brain oedema. High intensity brain trauma, seizures, osmotic forces, hypoxic conditions, and alteration of tight junctions proteins would explain the opening of endothelial junctions in severe and complicated brain oedema. In congenital hydrocephalus, the capillary wall shows evident signs of blood-brain barrier dysfunction characterized by closed and open interendothelial junctions, increased endothelial vesicular and vacuolar transport, thin and fragmented basement membrane with areas of focal thickening, and discontinuous perivascular astrocytic end-feet. The perivascular space is notably dilated and widely communicated with the enlarged extracellular space in the neuropil, showing the contribution of damaged endothelial junction to the formation of interstitial or hydrocephalic brain oedema. Altered expression of tight junction proteins could cause a blood-brain barrier breakdown following brain injury and hypoxic conditions leading to brain oedema. The results are compared with those found in experimental brain oedema. Some controversial results are also described. PMID- 22773458 TI - beta-amyloid (Abeta) deposition in cognitively normal brain, dementia with Lewy bodies, and Alzheimer's disease: a study using principal components analysis. AB - The densities of diffuse, primitive, and classic beta-amyloid (Abeta) deposits were studied in the temporal lobe in cognitively normal brain, dementia with Lewy bodies (DLB), familial Alzheimer's disease (FAD), and sporadic AD (SAD). Principal components analysis (PCA) was used to determine whether there were distinct differences between groups or whether Abeta pathology was more continuously distributed from group to group. Three principal components (PC) were extracted from the data accounting for 56% of the total variance. Plots of cases in relation to the PC did not result in distinct groups but suggested overlap in Abeta deposition between the groups. In addition, there were linear correlations between the densities of Abeta deposits and the distribution of the cases along the PC in specific brain regions suggesting continuous variation from group to group. PC1 was associated with the degree of maturation of Abeta deposits, PC2 with differences between FAD and SAD, and PC3 with the degree of spread of Abeta pathology into the hippocampus. Apolipoprotein E (APOE) genotype was not associated with variation in Abeta deposition between cases. PCA may be a useful method of studying the pathological interface between closely related neurodegenerative disorders. PMID- 22773459 TI - CD34/CXCR4 stem cell dynamics in acute stroke patients. AB - INTRODUCTION: Non-hematopoietic stem cells may be a source of paracrine and structural regeneration for brain damaged by acute ischemic stroke. In this study, we investigated correlations of CD34-, CD34/CXCR4-, and CXCR4-positive peripheral blood CD45-negative stem cells with the neurological and functional status of 34 acute stroke patients. MATERIAL AND METHODS: Blood was sampled and assessed by flow cytometry on days 1, 2, 4, and 6 after stroke onset. Parallel to blood sampling and after 3 and 6 months, patients were assessed with the National Institute of Health Stroke Scale, Barthel Index, Scandinavian Stroke Scale, and modified Rankin Scale. Blood was also sampled in 15 control subjects matched for age and sex, without history of previous stroke. RESULTS: We observed very low levels of the observed stem cells resident in peripheral blood. Higher baseline numbers of all 3 stem cell types correlated with better neurological or functional status on admission. Additionally, higher increases in CD34- and CD34/CXCR4-positive stem cell number and lower increase in CXCR4-positive cells correlated with initially worse neurological status. However, increased CD34- and CD34/CXCR4-positive cell induction in patients correlated with better functional/neurological status after the 6-month follow-up. CONCLUSIONS: We report that the number and dynamic changes in levels of non-hematopoietic CD34-, CD34/CXCR4-, and CXCR4-positive stem cells tend to correlate with acute stroke patients' neurologic and functional status. PMID- 22773461 TI - Familial cerebral cavernous malformation. AB - Cavernous malformations (CMs) occur in approximately 0.5% of the general population and represent 5-10% of the central nervous system vascular malformations. The majority of CMs appear sporadically but genetically determined familial forms account for 10% to 15% of all cases. The aim of this study was to discuss the clinical, pathological and genetic aspects of familial cerebral cavernous malformations (CCMs). We report on five members of a family who underwent surgery due to CCMs. However, only two members were treated in our Department. The age of onset of symptoms in these cases (4 men and 1 women) ranged from 3 to 28 years. Three members of the family were asymptomatic but it turned out that they were obligatory gene carriers and in one of them the cavernous malformation was confirmed by neuroimaging study. The clinical symptoms of CCMs included seizure (three patients) and focal neurological deficit (two patients). Multiple CCMs were identified in two symptomatic patients (two lesions) and in one asymptomatic patient (three lesions). The lesions were located superficially (4), in the basal ganglia (1), in the brainstem (2) and in the cerebellar vermis (1). In two patients, the subsequent imaging studies showed a single de novo CCM formation. Only one patient with mutation of CCM2 gene was treated surgically. In patients with cavernous malformations the detailed clinical and family history of neurological events ought to be collected. This is particular important in patients with multiple changes or with de novo CCMs formation, identified in subsequent imaging studies. A well-documented family history can help to establish the final diagnosis and makes it possible to offer all members of the family proper neurological and genetic care. PMID- 22773460 TI - Impact of the -174G/C interleukin-6 (IL-6) gene polymorphism on the risk of paediatric ischemic stroke, its symptoms and outcome. AB - OBJECTIVES: Ischemic stroke remains one of the top ten causes of death in children. There is evidence for the role of pro-inflammatory cytokines, such as IL-6 and the -174G>C promoter polymorphism of the IL-6 gene, in the occurrence and outcome of stroke in adults. The aim of the present study was to determine a possible association between the -174G>C IL-6 polymorphism and occurrence of paediatric stroke, its symptoms and outcome. MATERIAL AND METHODS: The study group consisted of 340 individuals: 80 stroke children, 122 parents of patients and 138 controls. The -174G/C polymorphism was genotyped using the RFLP method. For the analysis of the relationship between genotypes and stroke we used two alternative methods: the case-control model and the transmission test for linkage disequilibrium using data from families. RESULTS: We observed no differences in the transmission of alleles from parents to children. We also did not find any statistical differences in distribution of genotypes and alleles between patients and controls. However, the analysis showed that post-stroke epilepsy was genotype dependent. All children with epilepsy were G allele carriers and none of them was a CC homozygote whereas about 25% of children without epilepsy had the CC genotype. CONCLUSIONS: Our study did not show any associations between the IL-6 174 G>C polymorphism and the occurrence of stroke but we observed a relation between post-stroke epilepsy and the G allele carrier-state. PMID- 22773462 TI - Carotid atheromatous plaques' instability. Practical implication of morphologic assessment. AB - The only method giving the possibility of a thorough assessment of plaques instability, is a histologic examination. Three plaques categories were distinguished: unstable, potentially unstable and stable. The distribution of particular types of plaques was similar in symptomatic and asymptomatic patients. Over three quarters of lesions which could correspond to stable plaques in a macroscopic assessment, microscopically fulfilled the criteria for unstable or potentially unstable ones (the number of confirmed stable lesions vs the number of unconfirmed ones, 13 vs. 51 respectively, p < 0.0001). In a microscopic assessment made for all the plaques altogether, 52 plaques (58.4%) were considered unstable; 18 (20.2%) fulfilled the criteria for potentially unstable ones. The remaining 19 plaques (21.4%) were classified as plaques of stable structure. Unstable plaques constituted a significant majority (unstable vs potentially unstable and unstable vs. stable, p = 0.0006 and p = 0.0008 respectively). Due to the fact that majority of carotid atheromatous plaques appear to be unstable or potentially unstable because of the inflammation and related mechanisms, the role of the inflammatory-immunologic component of atherosclerosis should be used in prophylaxis of stroke and the new therapeutic concepts worked out. PMID- 22773463 TI - Coexistence of meningioma and schwannoma in the same cerebellopontine angle in a patients with NF2. AB - The coexistence of schwannoma and meningioma in the same cerebellopontine angle (CPA) is uncommon. Especially, the presence of a single mixed tumour composed of demarcated or intermingled components of schwannoma and meningioma tissue is extremely rare. Such a phenomenon is mainly reported in a patient with NF2 or with history of previous irradiation. We present two cases of simultaneous occurrence of schwannoma and meningioma in the same cerebellopontine angle in young adult patients with clinical manifestation of NF2. The first patient was a 18-year-old young man who presented with bilateral CPA tumours, spinal mass lesion and multiple, small, schwannoma-like lesions of the cauda equina. Both CPA tumours was initially diagnosed as schwannomas based on preoperative MR imagings, however right CPA tumour appeared to be composed of a well-circumscribed transitional meningioma located inside schwannoma of Antoni A and B type. The second patient, a young 16-year-old boy, presented bilaterall CPA tumours as well as many meningeal tumours supratentorially and infratentorially. Two adjacent tumours in the left CPA proved to be schwannoma and meningioma. In both cases, the different neoplastic components were confirmed by histopathological and immunohistochemical studies. The possible mechanism underlying the occurrence of such coexisting tumors of different histogenesis remains unclear. PMID- 22773464 TI - Differential expression of MMP-9 and AQP4 in human glioma samples. AB - BACKGROUND: Metalloproteinase-9 (MMP-9) and aquaporin-4 (AQP4) have been individually reported in glioma development. Here, we co-analyzed their expression in multiple forms of human glioma tissues graded from II to IV. MATERIAL AND METHODS: Levels of MMP-9 and AQP4 were evaluated on 50 resected human glioma tissues using immunohistochemistry. Protein levels of both molecules were evaluated by a staining score system based on the percentage of positive cells/staining degree in each dot section. The transwell method was also used to discriminate fast migrating cells and slow migrating cells, in which expression of both MMP-9 and AQP4 was investigated by using immunofluorescence. RESULTS: The staining score of MMP-9 displayed a positively tumor grade dependent manner, whereas AQP4 expression showed a negatively tumor grade dependent manner. The nuclear translocation of both molecules was observed in astrocytomas with glioblastoma transition, or glioblastoma tissues. Fast migrating cells contain more AQP4, whereas more MMP-9 was localized in slow migrating cells. CONCLUSIONS: Our findings suggest differential expression patterns of MMP-9 and AQP4 in different grades of gliomas. Nuclear translocation of MMP-9 and AQP4 may exert more functions in glioblastoma transition or deterioration. PMID- 22773465 TI - Ultrastructure of meningiomas: autophagy is involved in the pathogenesis of "intranuclear vacuoles". AB - We report here common ultrastructural findings in a short list of meningiomas. At the lower power magnification, a tumour consisted of elongated or round cells and innumerable cellular processes connected with diverse intercellular junctions. Nuclei presented no specific features, nucleoli were infrequently seen and heterochromatin was clumped beneath the nuclear membranes. In a case of clear cell meningioma, cells were of watery cytoplasm. Occasionally, immobile cilia, completely ensheathed by the cytoplasm and anchored by blepharoplasts were seen; as we did not encounter those rare cilia in cross-sections, no further insight into their inner microtubular-doublet structure was possible. The cytoplasm of the cells and the processes were filled with the intermediate filaments. In the intercellular space, collagen fibrils and electron-dense material was occasionally observed. The majority of the tumour samples were filled with processes. Several types of junctional complexes were observed. The most frequent were desmosomes and in the proper plane of section their whole pentalaminar structure was readily discernible. However, robust tonofilaments, as seen in epithelial neoplasms, were not observed. Those desmosomal junctions were either completely symmetric or asymmetric, but the exact symmetry could not be judged without the assistance of a goniometer. Some junctional complexes were more elaborate, with desmosomal junctions separated by a tight apposition of membranes, which suggests tight junctions. "Intranuclear vacuoles" well-visible even at low power were defined as indentation of the cytoplasm into the nucleus. Within these vacuoles, autophagic vacuoles and lysosomal bodies were seen, suggesting an active macroautophagy process. In 2 cases, severe lipidization of meningioma cell cytoplasm was observed. In a case of anaplastic meningioma, a mitotic figure was found. In another case, empty rectangular spaces in the cytoplasm, suggestive of pre-existing crystalloid structures, were seen. PMID- 22773466 TI - Cerebral amyloid angiopathy manifested as a brain tumour. Clinical and neuropathological characteristics of two cases. AB - We present two cases (female and male patients, aged 64 and 38, respectively) of focal mass lesions mimicking a brain tumour: one with cognitive function deficit, memory troubles, behavioral changes and left hemiparesis, the other with difficulty in orientation and right hemiparesis. General physical and neurological examinations, laboratory tests and neuroimaging were used to diagnose the cases. Both of them showed nonspecific changes in the brain tissue and the brain tumour was suspected. In the first case MRI scan revealed two pathological masses in the right frontal region and hemorrhagical focus with destructions inside lesions. Second patient's MRI scan revealed a pathological mass at the interface of the left temporal and occipital regions. The neurosurgical procedure was performed. The final diagnosis was established on the basis of neuropathological examination of postoperative material. On light microscopy examination a severe cerebral amyloid angiopathy (CAA) was revealed. Amyloidoma was excluded due to the absence of amorphous material and eosynophylic masses. Tumefactive CAA is a rare condition. These two cases of focal, tumefactive, masslike lesions of diffuse cerebral amyloid angiopathy are reported because of diagnostic dilemmas. In patients with history of memory disfunction, neurological deterioration and different multiple changes observed in CT and MRI scans, such as hemorrhagic infarcts and ischemic cerebral lesions, CAA should be suspected. The imaging findings make a distinction between tumefactive CAA and brain tumours like gliomas difficult. A differential diagnosis of CAA and amyloidoma plays a significant role in a neuropathological examination. PMID- 22773467 TI - The history of oxygen inhalation as a treatment for cluster headache. AB - OVERVIEW: Oxygen has been a generally accepted treatment method for cluster headache attacks ever since Kudrow (1981) conducted a controlled trial showing that oxygen was equally or even more effective than ergotamine injections. PURPOSE: The aim of the present study was to provide a historical perspective of oxygen treatment in cluster headache and to find the origin of this treatment. Oxygen for cluster headache was first described by Horton in 1952 and for migraine patients in 1940 by Alvarez. At the time, neither of the authors provided any reason why they chose for this treatment method. The vasoconstrictive effect of oxygen was not described by Horton until 1961. CONCLUSION: We suggest that these authors originally adhered to the vasoconstrictive theory of vascular headache that was prevalent in the early 20th century until Wolff demonstrated the contrary in the late 1930s. The early literature describes an analogy between angina pectoris and migraine, as both being due to vasoconstriction. As oxygen was described as a treatment for angina pectoris, this may be the reason why oxygen was tried for migraine and cluster headache at a time when they were not recognized as separate entities. Later it turned out to be more effective for cluster headache. PMID- 22773468 TI - Age-associated cartilage degeneration of the canine humeral head. AB - The goal of this study was to determine if cartilage lesions of the humeral head in adult dogs are the consequence of osteochondrosis dissecans or degenerative joint disease. A gross and histologic survey was performed of humeral head cartilage lesions of 155 dogs ranging in age from 1 week to 19 years. The humeral head and cartilage lesion size were measured for each dog. Cartilage lesions were classified as fibrillation, fissures, erosion, and/or eburnation. The area of each lesion was multiplied by a severity score (fibrillation and fissures 1, erosion 2, and eburnation 3) to create a combined score for each humeral head. Correlations between this combined lesion score and age, humeral head size, body weight, and body condition score were assessed using a Bonferroni-corrected alpha of .01. Twenty-six humeral heads were also evaluated histologically. Of the 155 dogs, 80 (52%) had gross lesions of the articular cartilage. The presence and severity of the articular cartilage lesions were positively correlated with age, humeral head size, body weight, and body condition score. The average age of dogs with cartilage lesions was 8.8 years, and 77/105 (74%) of adult dogs had cartilage lesions. Fifty dogs were 3 years of age or younger; 3 of those had cartilage lesions, 1 of which was osteochondrosis. These data indicate that cartilage erosion of the caudal humeral head in dogs is a common degenerative lesion acquired in adult large breed dogs; osteochondrosis dissecans does not precede the lesion in the vast majority of cases. PMID- 22773469 TI - Histomorphometry of feline chronic kidney disease and correlation with markers of renal dysfunction. AB - Chronic kidney disease is common in geriatric cats, but most cases have nonspecific renal lesions, and few studies have correlated these lesions with clinicopathological markers of renal dysfunction. The aim of this study was to identify the lesions best correlated with renal function and likely mediators of disease progression in cats with chronic kidney disease. Cats were recruited through 2 first-opinion practices between 1992 and 2010. When postmortem examinations were authorized, renal tissues were preserved in formalin. Sections were evaluated by a pathologist masked to all clinicopathological data. They were scored semiquantitatively for the severity of glomerulosclerosis, interstitial inflammation, and fibrosis. Glomerular volume was measured using image analysis; the percentage of glomeruli that were obsolescent was recorded. Sections were assessed for hyperplastic arteriolosclerosis and tubular mineralization. Kidneys from 80 cats with plasma biochemical data from the last 2 months of life were included in the study. Multivariable linear regression (P < .05) was used to assess the association of lesions with clinicopathological data obtained close to death. Interstitial fibrosis was the lesion best correlated with the severity of azotemia, hyperphosphatemia, and anemia. Proteinuria was associated with interstitial fibrosis and glomerular hypertrophy, whereas higher time-averaged systolic blood pressure was associated with glomerulosclerosis and hyperplastic arteriolosclerosis. PMID- 22773470 TI - Achieving nursing's goals: toward the next 70 years. PMID- 22773471 TI - [Prevalence and determinants of exclusive breastfeeding in the city of Serrana, Sao Paulo, Brazil]. AB - The objective of this cross-sectional and quantitative study was to identify the prevalence and determinants of exclusive breastfeeding among infants less than six months of age in the city of Serrana, Sao Paulo, Brazil in 2009. A validated semi-structured questionnaire was administered to the guardians of the children less than six months of age who attended the second phase of a Brazilian vaccination campaign against polio. Univariate and multivariate analysis presented in odds ratios and confidence intervals was accomplished. Of the total of 275 infant participants, only 29.8% were exclusively breastfed. Univariate analysis revealed that mothers who work outside the home without maternity leave, mothers who did not work outside the home, adolescent mothers, and the use of pacifiers have a greater chance of interrupting exclusive breastfeeding. In the multivariate analysis, mothers who work outside the home without maternity leave are three times more likely to wean their children early. Results provide suggestions for the redirection and planning of interventions targeting breastfeeding. PMID- 22773472 TI - [Motherhood in the shelter context: the perspectives of sheltered adolescents]. AB - The objective of this study is to describe the understanding that sheltered female adolescents have regarding motherhood and analyze their experience of this process from their perspective, for the purpose of identifying a support structure for young sheltered mothers. This exploratory and qualitative study was performed at two municipal shelters in Rio de Janeiro. The data were collected through focal groups performed with 10 sheltered adolescents. The content analysis of the data revealed two categories: Motherhood in adolescence: the perspective of the sheltered adolescent and Being a mother at the shelter: positive and negative experiences. Being a mother during adolescence is an ambivalent experience for the sheltered adolescents. The shelter is described as a supportive environment, but difficulties still exist in helping them to construct a healthy image of motherhood. There is a need to sensitize the social actors involved in terms of creating intersectoral interventions regarding the context and lifestyles of these youths, which could prevent vulnerability/disaffiliation of mother and child. PMID- 22773473 TI - [Body and sexuality during pregnancy]. AB - The objective of this ethnographic study was to understand how women experience their body's physiological processes during pregnancy and their effects on sexuality. The study involved seven women living in a poor neighborhood in Sao Paulo. Data collection was performed through participant observation and interviews using guiding questions. The data were presented in the narrative form and then organized into the following categories: realizing the changes in the body; living with the changes in the body; and feelings and sensations experienced in sexual life during pregnancy and imagining the body after pregnancy. The women referred to the changes in their bodies as discomforts, and expressed their concern that these changes would be permanent. They expressed they hoped that, after childbirth, their body would go back to what it was like before pregnancy and that they would recover their sexual desire. Recognition of these concerns is an essential tool to guarantee appropriate professional practices. PMID- 22773474 TI - [Self-reported urinary incontinence in the postpartum period: clinical characteristics]. AB - The objective of this cross-sectional study was to characterize the manifestations of self-reported urinary incontinence in the postpartum period. We interviewed 288 women who were clients of a teaching health center in Sao Paulo, between the months of January and August of 2009. The data showed that among the 71 incontinent women (24.6%), 44 (62%) reported stress urinary incontinence, 65 (91.5%) were aware of urine leakage, 33 women (46.5%) experienced urine loss more than once a week, and 24 (33.8%) reported persistent urinary incontinence at the time of interview. The severity classified as moderate urinary incontinence was identified in 53 women (74.7%). The findings highlight the importance of studies on urinary incontinence in the postpartum period, as well as approaching this issue in education and health care interventions with women in the reproductive stage. PMID- 22773475 TI - [The translation and adaptation of the Gaudenz-Fragebogen to the Brazilian culture]. AB - The article describes the translation and adaptation of the Gaudenz-Fragebogen, an instrument of German origin used to diagnose female urinary incontinence, to the Brazilian culture. The steps recommended by international literature were followed: translation, synthesis of translations, back translation, valuation of the synthetic version by a board of specialists and pre-test. The process of translation and adaptation was adequately accomplished, and the instrument was demonstrated to be easily understood.This instrument was used in other studies prior to the validation process, and using the instrument in other studies is crucial so that its measurement properties can be assessed. PMID- 22773476 TI - The effects of health interventions on dietary habits and physical measurements. AB - The objective of this study was to determine the effects of health interventions on dietary habits and physical measurements. This quasi-experimental intervention study was performed with health service clients. The individuals' dietary habits, anthropometric measurements and blood pressure (BP) were obtained and measured, and a Food Frequency Questionnaire was administered upon their enrollment in the service. Interventions included physical activity, nutritional education groups, and individual nutritional counseling. Effects were measured by repeating physical measurements and using the What's your diet like? test. A total of 167 participants (mean age=52.5 years, SD12.6 years; 92.8% women) were included in the study. Following the interventions, there was a reduction in systolic BP (P=0.02) and use of animal fats (P<0.01), as well as an increase in the percentages of individuals having a normal waist circumference and daily consumption of greens/vegetables and milk/dairy products (P<0.01). Participation in the interventions was effective in improving the clients' nutrition and health, demonstrating the importance of interventions that combine dietary practices and physical activity in the promotion of health. PMID- 22773477 TI - [Health beliefs regarding diet: a perspective of hypertensive black individuals]. AB - The objective of this descriptive-exploratory study was to identify the health beliefs of black individuals with hypertension regarding the barriers and benefits of diet for controlling the disease, including the sociodemographic factors associated with the health beliefs surrounding diet control. One hundred and six black adults with hypertension were interviewed using a specific instrument. The data were analyzed considering the percentages, frequency of the cases, scores and prevalence ratio. The global analysis of beliefs showed a preponderance of beliefs regarding the benefits of diet control. It was observed that men, younger individuals, lack of a partner and low educational level and income were related to the beliefs regarding the benefits of adopting a healthy diet. In conclusion, health promotion among the black population requires an interdisciplinary approach and specific health policies addressing this populations' needs, aimed at preventive and curative aspects. PMID- 22773478 TI - [An evaluation of anxiety and depression symptoms in fibromyalgia]. AB - The objective of this study was to identify the frequency of anxiety and depression symptoms by verifying the association between anxiety traits, current depression and anxiety symptoms in fibromyalgia patients. Interviews were performed with 60 subjects diagnosed with fibromyalgia at the Rheumatology Outpatient Clinic at Universidade Federal de Sergipe between August 2007 and March 2008, in which two questionnaires were administered: the Hospital Anxiety and Depression Scale (HADS) and the State-Trait Anxiety Inventory (STAI). The frequency of anxiety and depression symptoms was, respectively, 50% and 86% for individuals with fibromyalgia, and the mean trait-anxiety score was 59.38. An association was observed between trait and state anxiety. Anxiety and depression were frequent symptoms among patients with fibromyalgia. However, anxiety appeared as a secondary symptom to depression, appearing in a more severe form, and, therefore, this comorbidity should be more valued and studied. PMID- 22773479 TI - [Evaluation of microbial growth on single-use vitrectomy probes reprocessed in healthcare practice]. AB - The aim of this study was to evaluate the microbial growth on single-use vitrectomy probes reprocessed in healthcare practice. We investigated nine vitrectomy probes that had been reused and reprocessed using different methods. The samples were sectioned, individually, in portions of 3.5 cm, totaling 979 sampling units (extensions, connectors and vitrectomy cutters), which were inoculated in culture medium and incubated at 37o C for 14 days. The results showed microbial growth on 57 (5.8%) sample units, 25 of which had been sterilized using ethylene oxide, 16 by hydrogen peroxide plasma, and 16 by low temperature steam and formaldehyde. Seventeen microbial species were identified. The most prevalent were: Micrococcus spp., coagulase-negative Staphylococcus, Pseudomonas spp., and Bacillus subtilis. The reuse of single-use vitrectomy probes was shown to be unsafe, therefore this practice is not recommended. PMID- 22773480 TI - [The analysis of activities not performed by the nursing team regarding the diagnosis of ineffective breathing pattern in the elderly]. AB - The objective of this cross-sectional, descriptive study was to identify the activities of the Nursing Intervention Classification considered as priorities for an Ineffective Breathing Pattern and not performed for elderly inpatients of a teaching hospital in the state of Goias. The study participants were 43 nursing professionals, and data collection was performed in the period spanning October to December 2008, after receiving approval from the Ethics Committee. It was observed that among the 67 activities considered to be priorities for the referred diagnosis, only seven were performed by all of the participants; the other activities, with a varied frequency, were not performed, with the main reason cited being that a professional from a different area completed the activity. It is understood that the fact that the nursing staff does not perform these activities can cause lack of complete coverage in nursing care; therefore there is a need for a legal apparatus to describe the activities that comprise professional practice exclusive to nursing personnel and those activities that have an interdisciplinary nature. PMID- 22773481 TI - [The perception and understanding of health professionals and undergraduate students regarding aging and the elderly]. AB - This qualitative study was developed with 117 healthcare professionals and undergraduate students who were participants of a non-verbal communication training program in gerontology, with the objective to identify the perception and understanding of healthcare undergraduates and graduates regarding aging and the elderly. The results allowed the construction of the following categories: an evolution of life that brings a variety of experiences; natural, mysterious and with accumulated experiences; a decrease in overall happiness due to an increase in isolation; a time of valuing affection and respect; an inevitable stage including distress, prejudice, and limitations worthy of attention; a natural consequence of life; and the presence of disease and the global physiological process. Regarding perceptions of the elderly, the answers were classified as positive, negative, mixed and neutral. We considered that the understanding regarding the elderly and aging was limited and pessimist, indicating a need to become aware that one's views affect the way we relate to others. PMID- 22773482 TI - [An elderly couple and their long life raising four schizophrenic children]. AB - The objective was to identify, among parents of schizophrenics, elements of their daily life in coping with the disorder and the care offered and received through the health system. This is a field research, using thematic oral history. The parents of four patients with schizophrenia took part in this study. Interviews were conducted, recorded and transcribed, based on three instruments (two specific questionnaires and a field diary). Three categories were identified that reflect difficulties experienced in daily life: limitations in knowledge about schizophrenia; fatigue and burden with impairment of quality of life; and uncertainly about the future and resilience strengthened by faith in God. The concept of care was associated with technical procedures, revealing general satisfaction with the care received. The suffering related to living with schizophrenic relatives is intense, and professionals must be prepared to deal with these experiences of pain and suffering from patients with mental disorder and their relatives. PMID- 22773483 TI - [Communication strategies used by health care professionals in providing palliative care to patients]. AB - The objective of this study is to verify the relevance and utilization of communication strategies in palliative care. This is a multicenter qualitative study using a questionnaire, performed from August of 2008 to July of 2009 with 303 health care professionals who worked with patients receiving palliative care. Data were subjected to descriptive statistical analysis. Most participants (57.7%) were unable to state at least one verbal communication strategy, and only 15.2% were able to describe five signs or non-verbal communication strategies. The verbal strategies most commonly mentioned were those related to answering questions about the disease/treatment. Among the non-verbal strategies used, the most common were affective touch, looking, smiling, physical proximity, and careful listening. Though professionals have assigned a high degree of importance to communication in palliative care, they showed poor knowledge regarding communication strategies. Final considerations include the necessity of training professionals to communicate effectively in palliative care. PMID- 22773484 TI - [Community health agents and their experiences of pleasure and distress at work: a qualitative study]. AB - The objective of this study was to identify the situations that cause pleasure or distress at work among the Community Health Agents (CHA) in a city in Rio Grande do Sul state/Brazil. A qualitative study was performed with 24 agents as the participants. Data collection took place in 2009 through the use of focal groups, using the thematic analysis technique. The situations causing pleasure at work were: being recognized, solving problems, working with peers and being creative. Situations causing distress were: deficiencies in the health service; lack of knowledge regarding their roles; lack of recognition; the stress of teamwork; the obligation of living and working in the same area; daily living and becoming involved with the social problems of the community; and being exposed to violence, which resulted in fear. It was verified that there is a need for adopting interventions with a view to promoting better working conditions, professional satisfaction and the health of community agents. PMID- 22773485 TI - [The educational work of nurses in the Family Health Strategy: difficulties and perspectives on change]. AB - The objective of this study was to understand the difficulties and perspectives on change that nurses have identified in developing educational interventions in the Family Health Strategy (FHS). This is a qualitative, descriptive-exploratory study. The data were collected with 20 nurses working in the FHS of the 10th Regional Health District of Parana, by means of semi-structured interviews carried out in April 2010, which were subjected to content analysis. The results demonstrated that nurses face difficulties in developing health education strategies with the clients, healthcare team, and administrators, especially in regards to the lack of physical, material and financial resources. However, based on the difficulties they encounter, they seek alternatives to overcome them and suggest changes aimed at improving the delivery of primary health care to the population, particularly regarding educational practices. PMID- 22773486 TI - [The micropolitics of the work of health professionals in health centers: regarding the health needs of families]. AB - The objective of this study was to understand the strengths and limitations of the process of nursing work at a health center in terms of recognizing the health needs of the population. The methodological framework used was social research in the qualitative perspective, with discourse analysis based on hermeneutics dialectics and founded on the Theory of Praxis Interpretation of Community Health Nursing. The data were collected by means of semi-structured interviews, and the working processes of the teams were examined according to the Analyzing Flowchart of the Model of a Health Care Service. In conclusion, there are limitations in the daily working process of the nursing team regarding the recognition of the health needs of the population. Coping with these needs consisted of the identification of complications, relegating the social determinants of the poor life conditions associated with the health-disease process to a secondary concern. PMID- 22773487 TI - [Cartographic notes on the work in the Family Health Strategy: relationships between workers and the population]. AB - The objective of this intervention study was to map instituted and instituting movements present in the work of the Family Health Strategy in the development of their care practices. The theoretical framework is based on institutional analysis, using the schizoanalytic approach. Group meetings were carried out with the staff to discuss how they provided collective care in continuing health education. The study subjects were professionals from the team and students who were engaged in academic activity in the service. The average attendance was twelve people per meeting, and there were a total of eight meetings from March to July 2010. Data were grouped into two immanent strata: the relationships of the team and the relationship with clients. The strata point to the intersection of education and legal institutions and the social and technical division of labor. Collective thinking in groups appeared to be effective in denaturalizing established processes and interrogating places, knowledge and practices. PMID- 22773488 TI - [Cooperative interventions and the Interaction of Community Health agents within the family health team]. AB - This qualitative study examines the social relationships between the Community Health Agents (CHAs) and the Family Health team (FH), highlighting cooperative interventions and interactions among workers. A total of 23 participant observations and 11 semi-structured interviews were conducted with an FH team in a city in the interior of Sao Paulo, Brazil. The results revealed that CHAs function as a link in the development of operational actions to expedite teamwork. These professionals, while creating bonds, articulate connections of teamwork and interact with other workers, developing common care plans and bringing the team and community together, as well as adapting care interventions to meet the real needs of people. In communication practice, when talking about themselves they talk about the community itself because they are the community's representatives and spokespersons on the team. The conclusion is that the CHA may be a strategic worker if his/her actions include more political and social dimensions of work in healthcare. PMID- 22773489 TI - [The cultural aspects of the practice of Community Health Agents in rural areas]. AB - The daily practice of Community Health Agents (CHAs) is permeated with educational interventions aimed at preventive care and health promotion. The sociocultural universe of these professionals can affect the dynamics of their practice within the community, particularly in rural areas, where there is evidence that the population expects to obtain information relative to their health and/or disease by means of cultural rites. Based on a case study, we sought to analyze the influence of the cultural practices of the agents working in a rural area in the interior of the state of Minas Gerais. The analysis revealed the presence of a strong connection between the culture and their activities. Religious beliefs and knowledge developed from the fusion of biomedical information and values based on family tradition regarding the health disease process have a direct effect on their practices. It is emphasized that they have an important role as facilitators in the practice of health care, with a positive effect stemming from the similarity of their life experiences and inherited cultures with those of the clients, thus making it possible to develop effective interventions. PMID- 22773490 TI - [The experience of moral distress in nursing: the nurses' perception]. AB - With the objective to understand the nurses' perception of moral distress, as well as its frequency and intensity, this study used a survey utilizing a six point Likert scale, with 124 nurses working in hospitals in southern Brazil in 2008. Using a self-administered questionnaire and factorial analysis, four constructs were identified and validated. The final results were obtained through three different analyses: 1) descriptive statistical analysis; 2) analysis of variance; and 3) multiple regression. The construct that showed the highest intensity of perception regarding moral distress was the lack of competency in the work team (4.55), followed by the nurse's denial of their role as patient advocate (4.30), therapeutic obstinacy (3.60) and disrespecting the patient's autonomy (3.57). Regarding the perception of the frequency of moral distress, once again, the highlighted construct was the lack of competency within the work team (2.42), followed by therapeutic obstinacy (2.26), the nurse's denial of their role as patient advocate (1.71) and disrespecting the patient's autonomy (1.42). PMID- 22773491 TI - [Bipolar affective disorder: pharmacotherapeutic profile and adherence to medication]. AB - This cross-sectional and descriptive study aimed to verify the adherence of patients with Bipolar Affective Disorder (BAD) to medication and to identify possible causes of adherence and non-adherence to medication according to the pharmacotherapeutic profile. The study was carried out in a mental health service in a city in the interior of the state of Sao Paulo. Participants included 101 patients with BAD. Structured interviews and the Morisky-Green test were used for data collection, and the Statistical Package for Social Science was employed for data analysis. Most subjects (63%) did not adhere to medication. Although there were no significant differences between the adherent and non-adherent groups for the researched variables, the use of polypharmacotherapy and complex treatment regimens was observed in treatment for BAD. In practice, implementing strategies to improve the adherence of patients to medication treatment remains a challenge. PMID- 22773492 TI - Knowledge as a factor in vulnerability to tuberculosis among nursing students and professionals. AB - The objective of this study was to identify vulnerability to tuberculosis (TB) related to knowledge about the disease among 76 nursing students and professionals. A quantitative descriptive study was conducted using a closed questionnaire for the collection of data regarding transmission, preventive and biosafety measures, diagnosis, and prejudice regarding the disease. The SAS software version 9.1.3 was used for data analysis, with the level of significance set at 5% (p < 0.05). Nursing students and professionals showed a vulnerability to TB related to knowledge about transmission, preventive and biosafety measures, and diagnosis of the disease. With respect to transmission, vulnerability was higher among nursing professionals. The results indicate the need for investment by healthcare institutions surrounding this topic in view of the important role of nursing in the establishment of strategies for prevention and control of the disease. PMID- 22773493 TI - [Aids and tuberculosis: coinfection from the perspective of the quality of life of patients]. AB - Tuberculosis (TB) and HIV coinfection adversely affects the lives of individuals in both the biological and psychosocial aspects. Aiming to describe the quality of life of individuals with HIV/TB coinfection, this descriptive cross-sectional study was conducted in Ribeirao Preto-SP. Participants were HIV-seropositive individuals with and without TB, using the WHOQOL HIV BREF. 115 individuals who were HIV-positive participated: 57 were coinfected and 58 were not; most were male heterosexuals, predominantly aged 40-49 years. Of those coinfected, most had lower education and income. In assessing the quality of life the coinfected individuals showed lower results in all areas, with significant differences in the Physical, Psychological, Level of Independence and Social Relations areas. TB and HIV / AIDS are stigmatized diseases, and overlap of the two may have severe consequences on the physical and psychosocial health of the individual. PMID- 22773494 TI - [Knowledge, attitude and practices regarding condom use among women prisoners: the prevention of STD/HIV in the prison setting]. AB - The objective of this study was to evaluate the knowledge, attitude and practices of women prisoners regarding the use of female and male condoms as a means of prevention against STD/HIV. This quantitative and evaluative Knowledge, Attitude and Practice (KAP) study included 155 female prisoners. Data collection was performed between January and March 2010 at the State of Ceara Women's Penitentiary. Although the women had heard of and/or knew about the purposes of the use of condoms, only 35 (22.6%) had appropriate knowledge regarding male condoms, and 11 (7.1%) in regards to the use of female condoms. Their attitudes were less favorable regarding oral sex. Appropriate practice was not significantly representative, particularly regarding the female condom. Homo/bisexuality, gender issues, lack of knowledge, and the difficult access to condoms are obstacles that must be considered in the promotion of sexual health in the studied group. PMID- 22773495 TI - [Coping experiences in the work environment of men living with HIV/AIDS]. AB - The objective of this study was to understand the coping mechanisms of men living with HIV/AIDS in terms of their work environment. A qualitative study was carried out at a specialized outpatient clinic in Fortaleza-Ceara between March and June 2010, involving eleven men infected with the virus. Semi-structured and audio recorded interviews were used. The statements were categorized through content analysis into the following categories: absence from work due to the infection; subterfuges used to hide the disease; disrespect for confidentiality in the work environment; suffering associated with the fear of rejection and prejudice; ways of coping after diagnosis of the disease; and the importance of work for personal accomplishment. In conclusion, men infected with HIV face counterproductive situations in the work environment, mainly evidenced by fear of discovery of the infection and prejudice. Associated with coping, absences for health monitoring purposes interfered with performance at work and increased the risk of losing their job. PMID- 22773496 TI - [The construction process of managerial profile competencies for nurse coordinators in the hospital field]. AB - The objective of this study was to construct a profile of managerial competencies, based on the consensus of nurse coordinators in the field. This study was developed in a philanthropic hospital in Sao Paulo, following the research-action model, and included 13 nurse coordinators as participants. The data collection was performed using the focal group technique. Data analysis was performed using the theoretical frameworks related to the working process and managerial competencies. The results identified the greater emphasis assigned to the competencies related to the mentor, coordinator and director roles. It was, therefore, possible to construct a professional development plan that is based on competencies in the technical, ethical-political, and communicative domains, as well as the development of citizenship. The analysis of the managerial working process and the study of the competencies within the managerial environment were shown to be important, because they highlighted the professionals' need to improve, thus fulfilling personal, professional, and organizational demands. PMID- 22773497 TI - [Nursing care management in hospital settings: the building of a construct]. AB - The objective of this study was to build and present a theoretical definition of the concept of nursing care management in hospital settings, based on specific literature. We chose to use Concept Analysis strategies for building concepts, the rules of Archeological Analysis for forming concepts, and Lexical Analysis as the theoretical-methodological framework. The operationalization of the strategies and rules for forming the concept permitted the construction of the concept of nursing care in hospital settings. The constructed concept presented, by its nature, the capacity to form a dialectic integration of the aspects relative to the knowing-doing of care and management. The theoretical definition of the concept of Nursing Care Management in Hospital Settings assigned meaning to the term, in the initial context of the construction of a theory of Nursing Care Management in Health Services. PMID- 22773498 TI - [The academic education in nursing and multiple-victim incidents: an integrative review]. AB - The objective of this study is to reflect on the knowledge, competencies and skill that must be promoted during the academic education of nurses for an effective professional practice in view of a multiple-victim incident (MVI). This is an integrative literature review regarding academic nursing education. The literature survey was performed on the BDENF, LILACS, SciELO, MEDLINE, Web of Knowledge and HighWire Press databases, using the following descriptors: higher education; nursing education; emergency nursing; and mass casualty incidents. The publications permitted considerations regarding the following themes: particularities; competencies and skills essential in nursing practice in view of multiple-victim incidents; and the professors' strategies to promote those competencies and skills. The literature analysis demonstrated that nursing education should be configured as a space to develop critical thinking skills, which requires professors to have an eclectic educational background. PMID- 22773499 TI - [The use of fatty acids in wound care: an integrative review of the Brazilian literature]. AB - The objective of this study was to characterize the Brazilian scientific production on the topical use of fatty acids in wound care, and to describe the effects of its administration in this process. This integrative literature review included articles indexed in Lilacs and BEDENF databases. Data collection was carried out in December 2010 using controlled descriptors and without publication date limitations. The sample consisted of nine articles, mostly concerning animal models and the use of different fatty acids mixtures. Due to the lack of randomized clinical trials in human beings and the limitations of this review, it is not possible to generalize that essential fatty acids have a positive effect on the healing process or have antimicrobial effects on wound healing. Therefore, it is necessary to conduct studies of higher methodological rigor, comparing the different formulas available with fatty acids and their effects on the healing process. PMID- 22773500 TI - [Health education in the care to clients of the blood glucose self-monitoring program]. AB - This article reports, in a systemized and analytical way, the experience of an Outreach Program in the period between 2010 and 2011. The study focused on health education interventions as strategies to improve the adherence of individuals with insulin- dependent diabetes mellitus (IDDM), clients of a blood glucose self Monitoring program. In addition, we intended to contribute to the reorganization of the program's working processes in the unit. Health education strategies were used in both educational groups and home visits, thus permitting the provision of care that was more individualized. Data regarding the clients were organized on a spreadsheet and in files for the Family Health teams, which made it easier to identify the patients, including those who were absent, helping to decentralize the care. By using health education strategies, we intended to contribute to a more comprehensive and emancipatory care of the clients, aimed at a continuous reflection of the workers regarding their practices. PMID- 22773501 TI - [International Classification of Public Health Nursing Practices - CIPESC(r): a pedagogical tool for epidemiological studies]. AB - The CIPESC(r) is a tool that informs the work of nurses in Public Health and assists in prioritizing their care in practice, management and research. It is also a powerful pedagogical instrument for the qualification of nurses within the Brazilian healthcare system. In the teaching of infectious diseases, using the CIPESC(r) assists in analyzing the interventions by encouraging clinical and epidemiological thinking regarding the health-illness process. With the purpose in mind of developing resources for teaching undergraduate nursing students and encouraging reflection regarding the process of nursing work, this article presents an experimental application of CIPESC(r), using meningococcal meningitis as an example. PMID- 22773502 TI - [Thoughts regarding researchers utilizing Grounded Theory]. AB - This descriptive-reflexive study was performed with the objective to present the characteristics of researchers who use the Grounded Theory method, and outline the development of aptitudes for the researcher to become a Grounded Theoretician. The theoretical discussion was based on the frameworks of this methodology and supported by the literature. The article presents the main demands of qualitative studies using Grounded Theory, and important behaviors, attitudes and characteristics developed by the researchers. It is concluded that learning about Grounded Theory involves more than operationalizing a group of procedures and techniques. It also involves facing challenges to change one's attitude as a researcher and develop new ways of thinking and researching, gathering knowledge based on data to form a theory. PMID- 22773503 TI - Management of hip instability with a cemented, constrained acetabular component. AB - We evaluated the use of a cemented constrained acetabular component to treat recurrent or potential instability after hip replacement. Over a seven year period, 109 patients who had undergone 110 operations were identified from hospital records. Patients were reviewed based on clinical and radiological follow-up. Post-operative function and quality of life was assessed using the Oxford Hip Score (OHS) and SF-12. From an original cohort of 109 patients, 9 patients were lost to follow up. Of the remaining 100 patients, the mean follow up was 2.9 years (SD+/-2 years). There were 4 failures, requiring 3 further revisions. The mean post-operative OHS was 33, SF-12 PCS 34 and SF12 MCS 52. 5 year survivorship was 90%. Cementing a constrained acetabular component provides satisfactory mid term results in patients at high risk of hip dislocation. PMID- 22773504 TI - Increased range of motion to impingement with large head total hip arthroplasty: point of diminishing returns. AB - Large head total hip arthroplasty (THA) is known to increase range of motion to impingement and decrease risk of dislocation, however, this is dependent on accurate component positioning and patient anatomy. In this study, a computer aided design model was used to determine the effects of component positioning on range of motion to impingement with increasing head size. Three-dimensional models were made of 7 cadaver CT scans and virtual THA was performed with a conventional implant system. Theoretical range of motion to impingement was tested before and after the components were implanted in flexion, extension, internal/external rotation, abduction, adduction, and flexed internal/external rotation. Range of motion increased non-linearly in every motion except for external rotation and adduction with increasing head size, with gains in ROM limited by osseous impingement. Use of large head THA leads to increased ROM to impingement, but with larger head sizes, benefits are limited by bony anatomy. PMID- 22773505 TI - Effect of restoration of combined offset on stability of large head THA. AB - Improvements in bearing technology have resulted in a reduction in wear and larger femoral heads to reduce dislocation rates. We retrospectively reviewed 668 primary THAs (580 patients) inserted with 32 mm or 36 mm femoral heads (1/2003 6/2007) performed through a posterior approach with posterior repair. Patients received a questionnaire assessing instability and dislocations. We compared clinical and radiographic data between patients with and without dislocations. Follow-up averaged 3.4 years (range 2-6.6 years). The dislocation rate was 1.3% (9/668). Decreasing the combined postoperative offset (lateral offset + medial offset measurements) and using acetabular cups larger than 58 mm in outer diameter increased the risk of dislocation. A majority of the hips that dislocated had negative combined offset and abduction angles in the upper and lower quartiles of all hips studied. Appropriate positioning should be used to minimise dislocation risk in THAs inserted with large femoral heads. PMID- 22773506 TI - Meningiomas of the anterior portion of the craniovertebral junction: immediate and late outcome following surgical removal using a partial transcondylar approach. AB - BACKGROUND AND PURPOSE: The partial transcondylar approach (PTA) is an alternative to the suboccipital approach in the surgical treatment of meningiomas of the anterior portion of the craniovertebral junction (APCVJ). The purpose of this study is to present our results of treatment of these meningiomas using PTA. MATERIAL AND METHODS: Fourteen patients (11 women, 3 men) with meningioma of the APCVJ were included in the study. Neurological status of the patients was assessed before and after surgery as well as at the conclusion of the treatment. The approximate volume of the operated tumour, its relation to large blood vessels, cranial nerves and brainstem, along with its consistency and vascularisation were assessed. RESULTS: The symptom duration ranged from 1 to 36 months (median: 11 months). In 79% of patients, motor deficits of the extremities were predominant symptoms. Less frequent symptoms included headache, cervical pain and sensory deficits of cervical nerves C2 to C5. Approximate volume of the tumours ranged from 2.5 mL to 22.1 mL (mean: 11.7 mL). Gross total or subtotal resection was achieved in 86% of patients. The postoperative performance status improved in 57%, did not change in 36% and deteriorated in 7% of the patients. CONCLUSIONS: The PTA is a useful technique for removal of meningiomas expanding intradurally of the APCVJ without significant compression of the medulla. The results of treatment were good in most patients. PMID- 22773507 TI - Endoscopic technique in the treatment of patients with colloid cysts of the third ventricle. Report based on over a decade of experience. AB - BACKGROUND AND PURPOSE: The aim of the work was a retrospective analysis of the efficiency of endoscopic treatment of patients with colloid cysts of the third ventricle. MATERIAL AND METHODS: The analysis covered 17 patients. There were 19 operations in total. The follow-up period ranged from 21 to 130 months. The effectiveness of the method was evaluated by comparing neurological condition and magnetic resonance imaging (MRI) before and after treatment. RESULTS: The mean duration of surgery was 81 minutes. The cyst was removed completely in 8 patients, subtotally in 5, partially in 3, and in 1 case a biopsy was performed. No persistent intra- or postoperative complications or deaths occurred. Immediately after the operation symptoms withdrew completely in 8 patients and partially in 9. In the long term follow-up period, all symptoms receded completely in 11 patients and a further 6 patients showed partial improvement. MRI revealed the absence of the cyst in 8 patients, in 2 patients the tumor was smaller in size and in a further 7 patients some small parts of the walls of the cyst were present. The width of the ventricle system returned to its normal size in 8 patients, decreased in 8 patients and in 1 case remained at its initial size. In 2 patients temporary postoperative complications occurred. The average hospitalization time was 9 days. CONCLUSIONS: Recurrences of colloidal cysts after subtotal and partial removal do not occur very often, and the time of the recurrence may either be very long or it may not happen at all. Although we recommend complete removal of the cyst, this should not be pursued at the cost of incurring operative complications. PMID- 22773508 TI - Caregiver burden after stroke: towards a structural model. AB - BACKGROUND AND PURPOSE: Stroke may impose a severe burden on both the patients and their caregivers. Although there is substantial literature relating to the adverse impact of stroke on patients, considerably less is known about its impact on their caregivers. The aim of this study was to analyse predictive factors of the overall burden in caregivers of stroke victims and to verify the structural model of burden, built on the basis of theoretical and empirical assumptions. MATERIAL AND METHODS: One hundred and fifty pairs of patients and their caregivers were evaluated. The Caregiver Burden Scale (CB), Hospital Anxiety and Depression Scale (HADS), Sense of Coherence Scale (SOC), Social Support Scale, Geriatric Depression Scale, Barthel Index and Scandinavian Stroke Scale were all used to evaluate caregiver burden and the characteristics of patients and caregivers. RESULTS: The caregivers experienced a moderate burden (mean CB = 2.08) and emotional distress (mean total HADS = 14.1). Path analysis showed that higher burden was associated with a lower SOC score, higher emotional distress, and lower patient's functional status. Higher emotional distress, in turn, was associated with lower SOC and lower patient's functional status. These results show that the burden and the degree of emotional disturbance are two distinct negative consequences of caregiving. CONCLUSIONS: The negative consequences of caregiving depend mainly on the caregiver's intra-psychic factors and the patient's disability. Professional interventions should be targeted at enhancing caregivers' ability to cope with stress, improving their caregiving skills and reducing the physical dependence of patients. PMID- 22773509 TI - Accuracy of transcranial colour-coded sonography in the diagnosis of anterior cerebral artery vasospasm. AB - BACKGROUND AND PURPOSE: Transcranial colour-coded sonography (TCCS) has been proven to be a method of high performance in the diagnosis of spasm of the middle cerebral artery (MCA). Relevant data concerning the anterior cerebral artery (ACA) varies amongst studies. The aim of this study was to assess the performance of TCCS in the diagnosis of spasm affecting the ACA. MATERIAL AND METHODS: Ninety two patients (39 women and 53 men, age 51 +/- 12.1 years) were examined using TCCS before cerebral angiography. Of 184 examined ACAs, only 133 arteries could be visualized due to insufficiency of the temporal acoustic window. Therefore, only 15 out of 25 arteries in which vasospasm was diagnosed with angiography (by two neuroradiologists not informed about the sonographic findings) could be included in the analysis. Receiver operating characteristic (ROC) curves were constructed for specific blood flow velocities: peak systolic (PSV), mean (M) and end-diastolic (EDV). The area under the ROC curve was used to measure the overall diagnostic performance of TCCS. RESULTS: The area under the ROC curve for PSV was 0.83, which indicates good performance. The PSV threshold of 98 cm/s corresponded to maximum accuracy and was associated with 71% sensitivity vs. 88% specificity. Average systolic blood flow velocity in the vessels with vasospasm was 129 cm/s, whereas in unaffected vessels it was 76 cm/s. CONCLUSIONS: The accuracy of TCCS in the diagnosis of ACA spasm is relatively high - the value of the area under the ROC amounts to 0.83. PSV performs best and the threshold of 98 cm/s is associated with an optimal trade-off between sensitivity and specificity. PMID- 22773510 TI - Detection of cerebral artery fenestrations by computed tomography angiography. AB - BACKGROUND AND PURPOSE: Cerebral artery fenestrations (CAF) are rare congenital variations usually diagnosed by digital subtraction angiography (DSA). The aim of this study was to examine the frequency of occurrence of fenestrations in cerebral arteries and their coexistence with cerebral aneurysms in computed tomography angiography (CTA). MATERIAL AND METHODS: All reports of cerebral CTA (1140) performed in one institution from March 2005 to December 2007 were analysed. We found 40 patients with single fenestrations of the intracranial arteries. All 40 examinations were retrospectively reviewed for location of vascular malformations and presence of aneurysms or subarachnoid haemorrhage (SAH). Medical histories of those patients were then analysed for evidence of SAH and referral reasons for CTA. RESULTS: Forty fenestrated arteries were found in CTA: 18 basilar arteries (45%), 16 anterior cerebral arteries (40%), 4 anterior communicating arteries (10%) and one middle cerebral artery (2.5%). Only one vertebral artery fenestration was found due to the technique of the examination. Six patients (15%) with fenestrated arteries had a total of 8 aneurysms, although only one aneurysm was ipsilateral to the fenestration. In 8 cases of SAH, two were with no evidence of vascular malformation. The coexistence of CAF and aneurysms in CTA amounted to 15% (6/40), but the incidence of ipsilateral aneurysm was only 2.5% (1/40) and it affected the anterior cerebral artery. CONCLUSIONS: Basilar artery fenestration is the most frequent observed fenestration in CTA, followed by anterior cerebral artery and anterior communicating artery fenestrations. Coexistence of fenestration and aneurysm is uncommon in CTA examination. PMID- 22773511 TI - [Partial transcondylar approach - analysis of the surgical technique in cadaver simulation]. AB - The aim of the study was to present consecutive stages of the partial transcondylar approach. Six simulations of the partial transcondylar approach were performed on non-fixed human cadavers without any known pathologies in the head and neck. The consecutive stages of the procedure were documented with photographs and diagrams. The starting point for the partial transcondylar approach is a posterior repositioning of the suboccipital segment of the vertebral artery. The approach is achieved by partial removal of the occipital condyle and lateral mass of the atlas as well as by suboccipital craniectomy. Elevation of the cerebellar hemisphere presents an important supplement of the approach. The partial transcondylar approach is a reproducible technique, which provides surgical penetration of the anterior part of the cranio-cervical junction and related regions. This approach is particularly useful in the treatment of intradural tumours localized ventrally to the medulla. PMID- 22773513 TI - [Neuropathies in the course of primary hepatotropic virus infections]. AB - The primary hepatotropic viruses are associated with various extrahepatic manifestations including peripheral nervous system disorders. The pathogenesis of these complications is not clear-cut. Patients with confirmed liver damage coexisting with peripheral nervous system manifestations, especially Guillain Barre syndrome, mononeuropathy, mononeuropathy multiplex and polyneuropathy should be screened for the viral hepatitis in the differential diagnosis. There are no defined strategies of treatment for these manifestations, so the therapy should be individualized. The purpose of this review is to discuss the etiology, pathogenesis and treatment of the neuropathies in the course of primary hepatotropic viral infections such as hepatitis A, B, C and E viruses. PMID- 22773512 TI - [Elevated plasma creatine kinase activity - does it always indicate muscle disease?]. AB - Despite advanced diagnostic procedures in muscle disorders, creatine kinase (CK) activity is still one of the parameters most often investigated in serum. It is used mainly in neuromyology, and helps to differentiate between myogenic and neurogenic processes. Furthermore, it is applied to monitor the course of the disease and treatment results. Occasionally, marked elevated CK activity requires detailed diagnostic work-up, including electrophysiological, histopathological and genetic studies. In some cases, it enables the final diagnosis to be established. However, there is still a group of patients with so-called idiopathic hyper-CKemia and with no evidence of neuromuscular disorder. As little is known about potentially asymptomatic hyper-CK-emia, these patients should be carefully monitored. PMID- 22773514 TI - [Metabolic syndrome as the risk factor for ischaemic stroke]. AB - Metabolic syndrome (MetS) is a heterogeneous clinical entity represented by the occurrence of central obesity, hyperlipidaemia, hyperglycaemia and hypertension. The results of previous studies have shown that the probable common underlying pathophysiological factor for MetS is the insulin resistance phenomenon. However, the pathogenesis of the syndrome is still not well known. We present substantial information on MetS and the relationships between stroke and MetS as a compound entity, while individual components of MetS are well known risk factors for both first-in-life and recurrent ischaemic stroke. We also discuss primary and secondary stroke prevention in subjects with MetS. PMID- 22773515 TI - Bilateral paramedian thalamic infarction with hypothalamic dysfunction. AB - Unilateral thalamic lesions cause transient or permanent behavioral, sensory and oculomotor disturbances; bilateral lesions of thalamus result in more severe and longer lasting symptoms. We present an atypical case of bilateral paramedian thalamic infarct with concomitant hypothalamic dysfunction. The only risk factor of ischaemic stroke found in the patient was a short lasting episode of atrial fibrillation. Bilateral paramedian thalamic infarcts may result from occlusion of one paramedian thalamic artery, which arises from the posterior cerebral artery, either with separated or with a common trunk, thus supplying the thalamus bilaterally. Independently of anatomical variants of thalamus blood supply, the most probable cause of infarct in our patient was unilateral or bilateral occlusion of the posterior cerebral artery by cardioembolism, probably in the course of basilar artery occlusion. Hypothalamic dysfunction may accompany thalamic infarcts; thus hypothalamo-pituitary function should be routinely assessed in bithalamic infarcts. PMID- 22773516 TI - Guillain-Barre syndrome as the first manifestation of POEMS syndrome. AB - POEMS syndrome is a rare multisystem disorder, characterized by the presence of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes. The variety of clinical pictures and asynchronous manifestation of dominant features make diagnosis difficult. We report a case of a 42-year-old man with polyneuropathy who was initially negative for monoclonal protein and so Guillain-Barre syndrome was diagnosed. Other signs and symptoms, including monoclonal gammopathy, developed later in the course of the disease and finally POEMS syndrome was diagnosed. PMID- 22773518 TI - Gamma knife surgery-induced ependymoma after the treatment of meningioma - a case report. AB - Gamma knife surgery is widely used for a number of neurological disorders. However, little is known about its long-term complications such as carcinogenic risks. Here, we present a case of a radiosurgery-induced ependymoma by gamma knife surgery for the treatment of a spinal meningioma in a 7-year-old patient. In light of reviewing the previous reports, we advocate high caution in making young patients receive this treatment. PMID- 22773517 TI - [Anti-NMDA receptor encephalitis - case report]. AB - We present a patient with multiple sclerosis, diagnosed at the age of 16.5, in whom mental and orientation disturbances, strange behaviour as well as bizarre dyskinesias of the face and extremities occurred at age 20. After several days, tonic-clonic status epilepticus developed. Head computed tomography showed no abnormalities. Lumbar puncture revealed a pleocytosis of 20/3, which became normal after treatment. Seizures were brought under control, but the psychiatric symptoms persisted; they subsided after a dozen or so weeks. Magnetic resonance of the head and cervical spinal cord did not show any new abnormalities. After another several months, all symptoms recurred. A wide range of laboratory tests, as well as positron emission tomography, did not reveal any abnormalities. Suspicion of autoimmune encephalitis led to a test for serum anti-NMDA-receptor antibodies that confirmed the diagnosis. After immunotherapy, our patient improved and was transferred for rehabilitation. PMID- 22773519 TI - [Beginnings of the Neurosurgery Department of the Faculty of Medicine at the University of Warsaw and cooperation with the Montreal Neurological Institute]. PMID- 22773520 TI - Molecular pathways: context-dependent approaches to Notch targeting as cancer therapy. AB - Recent high-throughput genomic sequencing studies of solid tumors, including head and neck squamous cell carcinoma (SCC), ovarian cancer, lung adenocarcinoma, glioblastoma, breast cancer, and lung SCC, have highlighted DNA mutation as a mechanism for aberrant Notch signaling. A primary challenge of targeting Notch for treatment of solid malignancies is determining whether Notch signaling is cancer promoting or tumor suppressing for a specific cancer. We compiled reported Notch receptor and ligand missense and nonsense mutations to glean insights into aberrant Notch signaling. Frequencies of coding mutations differed for the 4 NOTCH genes. A total of 4.7% of tumors harbored NOTCH1 missense or nonsense mutations. NOTCH2, and NOTCH3 had similar overall mutation rates of 1.5% and 1.3%, respectively, whereas NOTCH4 mutations were rarer. Notch ligand genes were rarely mutated. The combined mutation frequency and position spectra of the 4 Notch paralogs across the different cancers provide an opportunity to begin to illuminate the different contributions of each Notch paralog to each tumor type and to identify opportunities for therapeutic targeting. Notch signaling pathway activators and inhibitors are currently in early clinical development for treatment of solid malignancies. Defining the status and consequences of altered Notch signaling will be important for selection of appropriate treatment. PMID- 22773522 TI - Reliability of thermal quantitative sensory testing: a systematic review. AB - The use of quantitative sensory testing (QST) has become more widespread, with increasing focus on describing somatosensory profiles and pain mechanisms. However, the reliability of thermal QST has yet to be established. We systematically searched the literature using key medical databases. Independent reviewers evaluated reliability data using the Quality Appraisal for Reliability Studies checklist. Of the 21 studies we included in this review, we deemed 5 to have high methodological quality. Narrative analysis revealed that estimates of reliability varied considerably, but overall, the reliability of cold and warm detection thresholds ranged from poor to excellent, while heat and cold pain thresholds ranged from fair to excellent. The methodological quality of research investigating the reliability of thermal QST warrants improvement, particularly in terms of appropriate blinding. The results from this review showed considerable variability in the reliability of each thermal QST parameter. PMID- 22773521 TI - Diagnostic performance of using one- or two-HbA1c cut-point strategies to detect undiagnosed type 2 diabetes and impaired glucose regulation within a multi-ethnic population. AB - INTRODUCTION: We compared test performance and cost per case for strategies detecting diabetes on the oral glucose tolerance test (OGTT) using either (a) glycated haemoglobin (HbA1c) >= 6.5% (48 mmol/mol) or (b) two HbA1c thresholds where the first cut-point 'rules out' and the second 'rules in' diabetes. HbA1c values in between the thresholds require confirmatory glucose testing for diagnosis. MATERIALS AND METHODS: We conducted an analysis of adults aged 40-75 years from the Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) cohort (Leicester, UK), from 2002 to 2008, who underwent oral glucose tolerance testing (OGTT) and HbA1c testing. RESULTS: From 8696 individuals (mean age 57.3 years, 73% white Europeans (WE) and 27% South Asians (SA)), HbA1c >= 6.5% produced sensitivity of 62.1% for detecting diabetes in WE and 78.9% in SA. Using two selected thresholds, HbA1c <= 5.8% (rule-in, 40 mmol/mol) and HbA1c >= 6.8% (rule out, 51 mmol/mol) produced high sensitivity/specificity (> 91.0%) for detecting diabetes, however, 28.8% of the cohort with HbA1c 5.9%-6.7% required a subsequent glucose test. The two cut-point threshold produced a lower cost per case of diabetes detected in WE, compared to HbA1c >= 6.5% of L38.53 (1.89 to 86.81) per case, but was more expensive in SA by L84.50 (69.72 to 100.92) per case. Using a risk score to determine HbA1c testing, the same costs per case became L63.33 (23.33 to 113.26) in WE and L69.21 (55.60 to 82.41) in SA. CONCLUSION: Using a two-threshold strategy may have some benefits over a single cut-point; however, 28.8% of individuals required two blood tests. PMID- 22773524 TI - Asymmetric lower-limb bone loss after spinal cord injury: case report. AB - Osteoporosis is a significant secondary condition that occurs acutely after spinal cord injury (SCI). This article reports on a patient with motor incomplete SCI and asymmetric lower-limb bone loss as it correlates with lower-limb motor function and gait characteristics. A 32-year-old Caucasian male completed a comprehensive inpatient rehabilitation program, including 3 months of robotic body-weight-supported treadmill training three times a week. Bone mineral density (BMD) was monitored up to 1.5 years post-SCI by dual-energy X-ray absorptiometry. Ground reaction forces were measured through an instrumented treadmill for bilateral weight-bearing comparison. At 1.5 years postinjury, neurological examination revealed thoracic 4 American Spinal Injury Association Impairment Scale D SCI with less strength, reduced weight bearing, and lower BMD in the more neurologically impaired leg. These results suggest that osteoporosis may vary according to severity of impairment within individuals and that monitoring lower limb BMD is especially important for patients who ambulate. PMID- 22773523 TI - New portable tool to screen vestibular and visual function--National Institutes of Health Toolbox initiative. AB - As part of the National Institutes of Health Toolbox initiative, we developed a low-cost, easy-to-administer, and time-efficient test of vestibular and visual function. A computerized test of dynamic visual acuity (cDVA) was used to measure the difference in visual acuity between head still and moving in yaw. Participants included 318 individuals, aged 3 to 85 years (301 without and 17 with vestibular pathology). Adults used Early Treatment of Diabetic Retinopathy Study (ETDRS) optotypes; children used ETDRS, Lea, and HOTV optotypes. Bithermal calorics, rotational chair, and light box testing were used to validate the cDVA. Analysis revealed that the cDVA test is reliable for static (intraclass correlation coefficient [ICC] >/= 0.64) and dynamic (ICC >/= 0.43-0.75) visual acuity. Children younger than 6 years old were more likely to complete cDVA with Lea optotypes, but reliability and correlation with ETDRS was better using HOTV optotypes. The high correlation between static acuity and light box test scores (r = 0.795), significant difference of cDVA scores between those with and without pathology (p 0.05). The colonoscopic lesions seen in 26 (93%) of the 28 veterans with SCI who underwent colonoscopies included diverticulae, internal hemorrhoids, and polyps. No relationship was found between colonoscopic lesion type and SCI lesion location or severity. A relationship was found between total colonoscopic lesions and duration of SCI (p < 0.001). Age-, sex-, and race/ethnicity-matched veterans without SCI (controls) who underwent colonoscopy for their GI complaints had more colonoscopic lesions than the veterans with SCI who underwent colonoscopies (p < 0.001). PMID- 22773528 TI - Exploratory study of perceived quality of life with implanted standing neuroprostheses. AB - Individuals with spinal cord injury (SCI) need options for negotiating architectural barriers, completing essential transfers, and accessing items on high shelves or in cupboards that cannot be reached from the wheelchair or safely managed with reachers. Case Western Reserve University (CWRU) and the Department of Veterans Affairs (VA) have developed an assistive technology device to assist individuals with SCI to stand and transfer. The 8-channel implanted CWRU-VA system enables persons with SCI to exercise, stand, and maneuver in the vicinity of their wheelchairs. Interventions that decrease barriers to mobility and participation can have a significant effect on an individual's perceived quality of life (QOL). This study uses a qualitative research methodology comprised of a series of semi-structured interviews to determine the effects on perceived QOL of an implanted 8-channel functional electrical stimulation (FES) system for standing after SCI. The results reveal that individuals with SCI currently using an implanted FES standing system perceived significant improvements in QOL related to the neuroprosthesis. Implanted neuroprostheses for standing have the potential to improve QOL for veterans living with SCI. PMID- 22773529 TI - Center of mass acceleration feedback control for standing by functional neuromuscular stimulation: a simulation study. AB - The potential efficacy of total body center of mass (COM) acceleration for feedback control of standing balance by functional neuromuscular stimulation (FNS) following spinal cord injury (SCI) was investigated. COM acceleration may be a viable alternative to conventional joint kinematics because of its rapid responsiveness, focal representation of COM dynamics, and ease of measurement. A computational procedure was developed using an anatomically realistic, three dimensional, bipedal biomechanical model to determine optimal patterns of muscle excitations to produce targeted effects upon COM acceleration from erect stance. The procedure was verified with electromyographic data collected from standing nondisabled subjects undergoing systematic perturbations. Using 16 muscle groups targeted by existing implantable neuroprostheses, we generated data to train an artificial neural network (ANN)-based controller in simulation. During forward simulations, proportional feedback of COM acceleration drove the ANN to produce muscle excitation patterns countering the effects of applied perturbations. Feedback gains were optimized to minimize upper-limb (UL) loading required to stabilize against disturbances. Compared with the clinical case of maximum constant excitation, the controller reduced UL loading by 43% in resisting external perturbations and by 51% during simulated one-arm reaching. Future work includes performance assessment against expected measurement errors and development of user-specific control systems. PMID- 22773530 TI - Evaluation of sensation evoked by electrocutaneous stimulation on forearm in nondisabled subjects. AB - Few studies are available in the literature on the sensations artificially created by dual-channel electrocutaneous stimulation. This study assessed the effect of a set of selected stimulation parameters on the sensations evoked by single- or dual-channel electrocutaneous stimulation. The investigated parameters included the stimulation site, the number of pulses, the number of stimulating channels (single- vs dual-channel), and the interleaved time between two channels. The modality, quality, location, and magnitude of the sensations were evaluated when the stimulations were applied on the forearm skin in 16 nondisabled subjects. Tactile perception was found to be induced more easily on the median and ulnar aspect than the dorsal and radial aspect of the forearm. Stimulation site significantly affected the magnitude of the sensation (p < 0.01). Dual-channel stimulation significantly increased the sensation magnitude (p < 0.05) only when the two electrodes were positioned closely. Moreover, a higher number of pulses evoked a movement perception more frequently and the interleaved time showed no significant effect on the magnitude of the sensation. The findings are expected to be useful for sensory substitution and augmentation applications. The results may also help improve users' acceptance of hand prostheses. PMID- 22773531 TI - Human distal sciatic nerve fascicular anatomy: implications for ankle control using nerve-cuff electrodes. AB - The design of neural prostheses to restore standing balance, prevent foot drop, or provide active propulsion during ambulation requires detailed knowledge of the distal sciatic nerve anatomy. Three complete sciatic nerves and branches were dissected from the piriformis to each muscle entry point to characterize the branching patterns and diameters. Fascicle maps were created from serial sections of each distal terminus below the knee through the anastomosis of the tibial and common fibular nerves above the knee. Similar branching patterns and fascicle maps were observed across specimens. Fascicles innervating primary plantar flexors, dorsiflexors, invertors, and evertors were distinctly separate and functionally organized in the proximal tibial, common fibular, and distal sciatic nerves; however, fascicles from individual muscles were not apparent at these levels. The fascicular organization is conducive to selective stimulation for isolated and/or balanced dorsiflexion, plantar flexion, eversion, and inversion through a single multicontact nerve-cuff electrode. These neuroanatomical data are being used to design nerve-cuff electrodes for selective control of ankle movement and improve current lower-limb neural prostheses. PMID- 22773532 TI - Matching initial torque with different stimulation parameters influences skeletal muscle fatigue. AB - A fundamental barrier to using electrical stimulation in the clinical setting is an inability to maintain torque production secondary to muscle fatigue. Electrical stimulation parameters are manipulated to influence muscle torque production, and they may also influence fatigability during repetitive stimulation. Our purpose was to determine the response of the quadriceps femoris to three different fatigue protocols using the same initial torque obtained by altering stimulator parameter settings. Participants underwent fatigue protocols in which either pulse frequency (lowHz), pulse duration (lowPD), or voltage (lowV) was manipulated to obtain an initial torque that equaled 25% of maximum voluntary isometric contraction. Muscle soreness was reported on a visual analog scale 48 h after each fatigue test. The lowHz protocol resulted in the least fatigue (25% +/- 14%); the lowPD (50% +/- 13%) and lowV (48% +/- 14%) protocols had similar levels of fatigue. The lowHz protocol resulted in significantly less muscle soreness than the higher frequency protocols. Stimulation protocols that use a lower frequency coupled with long pulse durations and high voltages result in lesser amounts of muscle fatigue and perceived soreness. The identification of optimal stimulation patterns to maximize muscle performance will reduce the effect of muscle fatigue and potentially improve clinical efficacy. PMID- 22773533 TI - Do diabetic neuropathy patients benefit from balance training? AB - Peripheral neuropathy is a common complaint of diabetes. Peripheral neural damage in turn will cause balance impairments in diabetic patients. The purpose of this study was to investigate the effects of balance exercises on sway indices in diabetic patients with neuropathy. In this clinical trial study, 10 diabetic patients with peripheral neuropathy were recruited through simple nonprobability sampling along with 10 nondisabled aged-matched subjects. Participants in both groups were examined for balance abilities with the Biodex Balance System before intervention. The experimental group was tested again after intervention. Intervention consisted of progressive Biodex stability and rocker and wobble board training for 10 sessions. All tests were done in eyes open and closed conditions with bilateral standing. After intervention, the experimental group was re-examined in the same way. Student and paired t-tests were used for data analysis. The overall stability index and anterior-posterior stability index were significantly decreased after treatment in the experimental group during different conditions. Balance indices in the experimental group were significantly higher than the control group before treatment. There was no significant difference in indices between the two groups after treatment. The results show that balance training can improve stability indices in diabetic patients with neuropathy. PMID- 22773534 TI - Card sort methodology: an objective measure in rehabilitation research. PMID- 22773535 TI - Heat illness surveillance in schoolboys participating in physical education class in tropical climate: an analytical prospective descriptive study. AB - OBJECTIVES: This study aimed to determine thermoregulatory and cardiovascular responses as well as the occurrence of heat illness in children exercising outdoors in physical education class under hot and humid climate. Little information regarding this issue under real-life situation is available, especially in the Southeast Asia. DESIGN: Analytical, prospective descriptive study. SETTING: A primary school in Bangkok, Thailand. PARTICIPANTS: A total of 457 schoolboys (aged 5.5-12 years) were observed while exercising outdoors during their physical education classes throughout the academic year of 2009, including semester 1 (between July and September 2009) and semester 2 (between November 2009 and February 2010). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was tympanic temperature. Secondary outcome measures included blood pressure, heart rate, hydration status and the occurrence of heat-related illness. RESULTS: Outdoor physical activity consisted of skill practice (duration 24.11+/-11.04 min, intensity <3 metabolic equivalent of tasks) and playing sports (duration 11.48+/-5.53 min, intensity 2.6-8.8 metabolic equivalent of tasks). After exercise, tympanic temperature increased by 0.66+/-0.41 degrees C. There were 20 (4.4%) students whose ear temperature exceeded 38 degrees C, 18 of whom did not consume water. The RR of increasing body temperature up to 38 degrees C in overweight students was 2.1-fold higher than normal-weight students. The per cent change in mean arterial pressure and heart rate increased by 20.16+/-15.34% and 23.94+/-19.78%, respectively. Sweat and dehydration rates were 391.16+/ 186.75 ml/h and 0.63+/-0.26%, respectively. No evidence of heat illness was found. Wet bulb globe temperatures of semesters 1 and 2 were 29.95+/-1.87 degrees C and 28.32+/-2.39 degrees C, respectively. CONCLUSIONS: There is an increased risk for heat illness during outdoor activities in physical education class in primary school children, especially those who are overweight and have poor hydration status. PMID- 22773536 TI - A case-control study on risk factors associated with death in pregnant women with severe pandemic H1N1 infection. AB - OBJECTIVES: To describe the risk factors associated with death in pregnant women with severe pandemic H1N1 infection. DESIGN: Case-control study. SETTING: Anhui, China. PARTICIPANTS: A total of 46 pregnant women with severe pandemic H1N1 infection were studied during June 2009-April 2011. PRIMARY AND SECONDARY OUTCOME MEASURES: All the cases were confirmed by the clinicians and epidemiologists together based on the positive laboratory result. RESULTS: Of the seven pregnant women who died of the pandemic H1N1 infection, five (70%) cases were in their third trimester. Twenty-nine (63%) cases from the surviving group were admitted to hospital within 3 days after the onset of symptoms, while only one (2%) case from the death group took the earliest admission 2 days after the onset. There was a significant difference on how soon to be admitted between the death and the surviving groups (OR 0.09, 95% CI 0.01 to 0.68). The median time of administrating corticosteroids was 5 days after the onset in the death group and 3 days in the surviving group showing no significant difference between them (p=0.056). CONCLUSIONS: For the pregnant women with severe p(H1N1) infection, the risk factors associated with death were as follows: the delay of antiviral treatment and being in the third trimester. The corticosteroids therapy appeared to have no effects on preventing the cases from death. PMID- 22773537 TI - Stroke and mortality in patients with incident heart failure: the Diet, Cancer and Health (DCH) cohort study. AB - OBJECTIVE: The objective was to test the hypothesis that the risk of stroke, death and the composite of 'stroke and death' would be increased among patients with incident heart failure (HF). While HF increases the risk of mortality, stroke and thromboembolism in general, the 'extreme high-risk' nature of incident HF is perhaps under-recognised in everyday clinical practice. DESIGN: Prospective cohort study. SETTING: Large Danish prospective epidemiological cohort. PARTICIPANTS: Subjects in the Diet, Cancer and Health study. OUTCOME MEASURES: Stroke, death and the composite of 'stroke and death' among patients with incident cases of HF, without concomitant atrial fibrillation. RESULTS: From the original cohort, 1239 patients with incident HF were identified. Incidence rates show a higher incidence in the initial period following the diagnosis of HF, with a markedly higher rate of death and stroke (ischaemic or haemorrhagic) in the initial 30 days following the diagnosis of incident HF. While lower than the risk at 0-30 days, the higher risk did not return to normal at 6+ months after the diagnosis of incident HF. This risk increase was apparent for the end points of stroke (ischaemic or haemorrhagic or both) whether or not a vitamin K antagonist (VKA) was used. With VKA use, there was a lower adjusted HR for death and the composite of 'death or stroke' compared to non-VKA use at the three time intervals following diagnosis of HF, whether 0-30 days, 30 days to 6 months and 6+ months. On multivariate analysis, previous stroke/transient ischaemic attack/thromboembolism was a predictor of higher risk of stroke, death and the composite of 'stroke and death', while VKA treatment was a highly significant predictor of a lower risk for death (adjusted HR 0.46, 95% CI 0.28 to 0.74, p<0.001) and the combined end point of death or stroke (adjusted HR 0.64, 95% CI 0.43 to 0.96, p=0.003). CONCLUSIONS: Based on relative hazards, incident HF is clearly a major risk factor for stroke, death and the composite of 'stroke and death', especially in the initial 30 days following initial diagnosis. The use of VKA therapy was associated with a lower risk of these end points. These findings would have major implications for the approach to management of patients presenting with incident HF, given the high risk of this population for death and stroke, which may be ameliorated by VKA therapy. PMID- 22773538 TI - Exposure to hot and cold temperatures and ambulance attendances in Brisbane, Australia: a time-series study. AB - OBJECTIVES: To investigate the effect of hot and cold temperatures on ambulance attendances. DESIGN: An ecological time-series study. SETTING AND PARTICIPANTS: The study was conducted in Brisbane, Australia. The authors collected information on 783 935 daily ambulance attendances, along with data of associated meteorological variables and air pollutants, for the period of 2000-2007. OUTCOME MEASURES: The total number of ambulance attendances was examined, along with those related to cardiovascular, respiratory and other non-traumatic conditions. Generalised additive models were used to assess the relationship between daily mean temperature and the number of ambulance attendances. RESULTS: There were statistically significant relationships between mean temperature and ambulance attendances for all categories. Acute heat effects were found with a 1.17% (95% CI 0.86% to 1.48%) increase in total attendances for 1 degrees C increase above threshold (0-1 days lag). Cold effects were delayed and longer lasting with a 1.30% (0.87% to 1.73%) increase in total attendances for a 1 degrees C decrease below the threshold (2-15 days lag). Harvesting was observed following initial acute periods of heat effects but not for cold effects. CONCLUSIONS: This study shows that both hot and cold temperatures led to increases in ambulance attendances for different medical conditions. Our findings support the notion that ambulance attendance records are a valid and timely source of data for use in the development of local weather/health early warning systems. PMID- 22773539 TI - The human salivary RNA transcriptome revealed by massively parallel sequencing. AB - BACKGROUND: Evaluation of the salivary transcriptome is an emerging diagnostic technology with discriminatory power for disease detection. This study explored massively parallel sequencing for providing nucleotide-level sequence information for each RNA in saliva. METHODS: Transcriptome profiling with the SOLiDTM system was applied to RNA isolated from unstimulated cell-free saliva (CFS) and whole saliva (WS) from healthy human volunteers. Sequenced reads were aligned to human genome build 18 and the Human Oral Microbiome Database (HOMD). RESULTS: Massively parallel sequencing enabled the acquisition of complete sequence information for each nucleotide position of the human salivary transcriptome through alignment to multiple sequence databases. Approximately 20%-25% of the sequenced reads from CFS aligned to the human genome, and approximately 30% of the sequenced reads aligned to the HOMD. We detected the expression of >4000 coding and noncoding genes in CFS and WS. Gene expression at different genome loci showed that the structural integrity of the transcripts for the annotated genes was preserved in saliva. CONCLUSIONS: A single measurement provided RNA sequence information of gene transcript abundance for both coding and noncoding RNAs and identified sequences from >400 different microbial species within a single sample. Contrary to previous data suggesting that salivary RNA is highly fragmented, in our study the structural integrity of RNA was preserved. The high degree of sequence alignment to annotated exons and introns for each of the respective reference genomes, with sequence coverage spanning the full length of the genes, provides strong evidence that the salivary transcriptome is a complex RNA network. PMID- 22773541 TI - Longitudinal changes of outcome measures in spinal and bulbar muscular atrophy. AB - Spinal and bulbar muscular atrophy is an adult-onset, hereditary motor neuron disease caused by the expansion of a trinucleotide CAG repeat within the gene encoding the androgen receptor. To date, several agents have been shown to prevent or slow disease progression in animal models of this disease. For the translational research of these agents, it is necessary to perform the detailed analysis of natural history with quantitative outcome measures and to establish sensitive and validated disease-specific endpoints in the clinical trials. To this end, we performed a prospective observation of disease progression over 3 years in 34 genetically confirmed Japanese patients with spinal and bulbar muscular atrophy by using quantitative outcome measures, including functional and blood parameters. The baseline evaluation revealed that CAG repeat length in the androgen receptor gene correlated not only with the age of onset but also with the timing of substantial changes in activity of daily living. Multiple regression analyses indicated that the serum level of creatinine is the most useful blood parameter that reflects the severity of motor dysfunction in spinal and bulbar muscular atrophy. In 3-year prospective analyses, a slow but steady progression was affirmed in most of the outcome measures we examined. In the analyses using random coefficient models that summarize the individual data into a representative line, disease progression was not affected by CAG repeat length or onset age. These models showed large interindividual variation, which was also independent of the differences of CAG repeat size. Analyses using these models also demonstrated that the subtle neurological deficits at an early or preclinical stage were more likely to be detected by objective motor functional tests such as the 6-min walk test and grip power or serum creatinine levels than by functional rating scales, such as the revised amyotrophic lateral sclerosis functional rating scale or modified Norris scale. Categorization of the clinical phenotypes using factor analysis showed that upper limb function is closely related to bulbar function, but not to lower limb function at baseline, whereas the site of onset had no substantial effects on disease progression. These results suggest that patients with spinal and bulbar muscular atrophy show a slow but steady progression of motor dysfunction over time that is independent of CAG repeat length or clinical phenotype, and that objective outcome measures may be used to evaluate disease severity at an early stage of this disease. PMID- 22773542 TI - Antioxidant properties, chemical composition and nutritional value of Terfezia boudieri (Chatin) from Turkey. AB - Our objectives were to investigate the chemical composition, nutritive value and antioxidant activity potentials of Terfezia boudieri Chatin collected from different areas from Southeast of Turkey. The amounts of energy, protein, fat, carbohydrate, crude fibre, moisture and ash were 34.00-65.00 (kcal/100 g), 1.40 2.73, 0.86-1.71, 4.84-11.60, 80.86-90.33 (g/100 g, f.w.) and 1.02-1.98 g/100 g dry mass, respectively. Fatty acids and amino acids analyses revealed that linoleic acid and glutamic acid were, respectively the most abundant. Among the essential amino acids leucine was the highest amount and this was followed by threonine. Magnesium was the most abundant element with a concentration value of 182.30 mg/100 g dry mass. T. boudieri exhibited excellent antioxidant activity when compared with standard compounds. In total antioxidant and chelating effect on ferrous ions activity T. boudieri showed the highest activity against the standards. Additionally, at all studied tests antioxidant activity of the mushroom increased with increasing concentration. The total phenolic content of T. boudieri was found as 8.45 mg/g. PMID- 22773540 TI - Regional fMRI hypoactivation and altered functional connectivity during emotion processing in nonmedicated depressed patients with bipolar II disorder. AB - OBJECTIVE: Although the amygdala and ventrolateral prefrontal cortex have been implicated in the pathophysiology of bipolar I disorder, the neural mechanisms underlying bipolar II disorder remain unknown. The authors examined neural activity in response to negative emotional faces during an emotion perception task that reliably activates emotion regulatory regions. METHOD: Twenty-one nonmedicated depressed bipolar II patients and 21 healthy comparison subjects underwent functional MRI (fMRI) while performing an emotional face-matching task. Within- and between-group whole-brain fMRI activation and seed-based connectivity analyses were conducted. RESULTS: In depressed bipolar II patients, random effects between-group fMRI analyses revealed a significant reduction in activation in several regions, including the left and right ventrolateral prefrontal cortices (Brodmann's area [BA] 47) and the right amygdala, a priori regions of interest. Additionally, bipolar patients exhibited significantly reduced negative functional connectivity between the right amygdala and the right orbitofrontal cortex (BA 10) as well as the right dorsolateral prefrontal cortex (BA 46) relative to healthy comparison subjects. CONCLUSIONS: These findings suggest that bipolar II depression is characterized by reduced regional orbitofrontal and limbic activation and altered connectivity in a fronto-temporal circuit implicated in working memory and emotional learning. While the amygdala hypoactivation observed in bipolar II depression is opposite to the direction seen in bipolar I mania and may therefore be state dependent, the observed orbitofrontal cortex hypoactivation is consistent with findings in bipolar I depression, mania, and euthymia, suggesting a physiologic trait marker of the disorder. PMID- 22773545 TI - Protein, protein everywhere ... but none to keep. PMID- 22773543 TI - Textural, physicochemical and sensory properties compensation of fat replacing in pork liver pate incorporating emulsified canola oil. AB - Saturated animal fat was replaced in pork pate with pre-emulsified canola in a 3% sodium caseinate/0.5% xanthan gum solution in order to obtain a stable oily phase. Fat was replaced with different proportions of emulsified canola oil. The inclusion of emulsified oil in pate enhanced cocking yield and moisture but increased fluids release. Nonetheless, total fat content remained practically constant, meaning no detrimental effect on caloric content. Replacing 50% of lard with emulsified oil did not affect color of the samples. Texture was improved since emulsified oil addition resulted in softer and more spreadable pate. Samples with 50% of emulsified oil were more stable to lipid oxidation at 8 days of storage, with lower thiobarbituric acid-reactive substances and volatile compounds resulting from oxidation reactions. Emulsified canola can be employed to replace fat until 50% in pate or liver sausage with good functional properties, improving texture and reducing lipids rancidity. PMID- 22773546 TI - A systematic approach to therapeutic target selection in oesophago-gastric cancer. AB - OBJECTIVE: The success of personalised therapy depends on identification and inhibition of the oncogene(s) on which that tumour is dependent. We aimed to determine whether a receptor tyrosine kinase (RTK) array could be used to select the most effective therapeutic strategies in molecularly heterogeneous oesophago gastric adenocarcinomas. DESIGN: Gene expression profiling from oesophago-gastric tumours (n=75) and preinvasive stages (n=57) identified the active signalling pathways, which was confirmed using immunohistochemistry (n=434). RTK arrays on a cell line panel (n=14) determined therapeutic targets for in vitro cytotoxic testing. Feasibility of this personalised approach was tested in tumour samples (n=46). RESULTS: MAPK was the most frequently activated pathway (32/75 samples (42.7%)) with progressive enrichment in preinvasive disease stages (p<0.05) and ERK phosphorylation in 148/434 (34.3%) independent samples. Cell lines displayed a range of RTK activation profiles. When no RTKs were activated, tyrosine kinase inhibitors (TKIs) and a Mek inhibitor were not useful (MKN1). In lines with a dominant phosphorylated RTK (OE19, MKN45 and KATOIII), selection of this TKI or Mek in nM concentrations induced cytotoxicity and inhibited Erk and Akt phosphorylation. In cells lines with complex activation profiles (HSC39 and OE33), a combination of TKIs or Mek inhibition (in nM concentrations) was necessary for cytotoxicity and inhibition of Erk and Akt phosphorylation. Human tumours demonstrated diverse activation profiles and 65% of cases had two or more active RTKs. CONCLUSIONS: The MAPK pathway is commonly activated in oesophago gastric cancer following activation of a variety of RTKs. Molecular phenotyping can inform a rational choice of targeted therapy. PMID- 22773547 TI - A novel mouse model of veno-occlusive disease provides strategies to prevent thioguanine-induced hepatic toxicity. AB - OBJECTIVE: The anti-leukemic drugs, azathioprine and 6-mercaptopurine (6MP), are important in the treatment of inflammatory bowel disease but an alternative faster-acting, less-allergenic thiopurine, 6-thioguanine (6TG), can cause hepatic veno-occlusive disease/sinusoidal obstructive syndrome (SOS). Understanding of SOS has been hindered by inability to ethically perform serial liver biopsies on patients and the lack of an animal model. DESIGN: Normal and C57Bl/6 mice with specific genes altered to elucidate mechanisms responsible for 6TG-SOS, were gavaged daily for upto 28d with 6TG, 6MP or methylated metabolites. Animal survival was monitored and at sacrifice a histological score of SOS, haematology and liver biochemistry were measured. RESULTS: Only 6TG caused SOS, which was dose related. 6TG and to a lesser extent 6MP but not methylated metabolites were associated with dose-dependent haematopoietic toxicity. SOS was not detected with non-lethal doses of 6TG. SOS did not occur in hypoxanthine-phosphoribosyl transferase-deficient C57Bl/6 mice, demonstrating that 6TG-SOS requires thioguanine nucleotides. Hepatic inflammation was characteristic of SOS, and C57Bl/6 mice deficient in P- and E-selectins on the surface of vascular endothelial cells showed markedly reduced SOS, demonstrating a major role for leukocytes recruited from blood. Split dosing of 6TG markedly attenuated SOS but still effected immunosuppression and prevented spontaneous colitis in Winnie mice, which have a single nucleotide polymorphism mutation in Muc2. CONCLUSION: This novel model provides clinically relevant insights into how 6TG induces SOS, and how this dangerous adverse drug reaction may be avoided by either inhibition of endothelial activation or simple changes to dosing regimens of 6TG, while still being effective treatment for colitis. PMID- 22773548 TI - Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies. AB - OBJECTIVE: Type 2 diabetes mellitus is associated with a higher risk of hepatocellular carcinoma (HCC), which is attenuated by the use of metformin. However, there are no studies addressing the effect of metformin on hepatocarcinoma cells from the antitumoural perspective. DESIGN: In the nationwide case-control study, the authors recruited 97,430 HCC patients and 19,860 age-, gender- and physician visit date-matched controls. The chemopreventive effects of metformin were examined by multivariate analysis and stratified analysis. The in vitro effects of metformin on cell proliferation and cell cycle were studied in HepG2 and Hep3B hepatoma cell lines. RESULTS: The OR of diabetes in HCC patients was 2.29 (95% CI 2.25 to 2.35, p<0.001). Each incremental year increase in metformin use resulted in 7% reduction in the risk of HCC in diabetic patients (adjusted OR=0.93, 95% CI 0.91 to 0.94, p<0.0001). In the multivariate stratified analysis, metformin use was associated with a reduced risk of HCC in diabetic patients in nearly all subgroups. Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose dependent manner, but independent of p53. Combined treatment of oral metformin with doxorubicin functioned more efficiently than either agent alone, in vivo. CONCLUSIONS: Use of metformin is associated with a decreased risk of HCC in diabetic patients in a dose-dependent manner, via inhibition of hepatoma cells proliferation and induction of cell cycle arrest at G0/G1 phase. PMID- 22773549 TI - Heterogeneity in mouse spasmolytic polypeptide-expressing metaplasia lineages identifies markers of metaplastic progression. AB - OBJECTIVES: Spasmolytic polypeptide-expressing metaplasia (SPEM) develops as a preneoplastic lesion in the stomachs of mice and humans after parietal cell loss. To identify the commonalities and differences between phenotypic SPEM lineages, SPEM were studied from three different mouse models of parietal cell loss: with chronic inflammation with Helicobacter felis infection; with acute inflammation with L635 treatment; and without inflammation following DMP-777 treatment. DESIGN: RNA transcripts from laser capture microdissected normal chief cells and SPEM lineages were compared using gene microarray. Alterations in transcripts were validated by quantitative real-time PCR. Clusterin and cystic fibrosis transmembrane conductance regulator (CFTR) were selected for immunohistochemical analysis in all mouse models as well as in human SPEM, intestinal metaplasia and gastric cancer. RESULTS: Transcript expression patterns demonstrated differences among the phenotypic SPEM models. Clusterin expression was significantly upregulated in all three mouse SPEM models as well as in human SPEM. The highest clusterin expression in human gastric cancers correlated with poor survival. Conversely, CFTR expression was upregulated only in SPEM with inflammation in mice. In humans, intestinal metaplasia, but not SPEM, expressed CFTR. CONCLUSIONS: While markers such as clusterin are expressed in all phenotypic SPEM lineages, distinct patterns of upregulated genes including CFTR are present in murine metaplasia associated with inflammation, indicative of progression of metaplasia towards a more intestinalised metaplastic phenotype. PMID- 22773550 TI - Extrapancreatic necrosis without pancreatic parenchymal necrosis: a separate entity in necrotising pancreatitis? AB - OBJECTIVE: In the revised Atlanta classification of acute pancreatitis, the term necrotising pancreatitis also refers to patients with only extrapancreatic fat necrosis without pancreatic parenchymal necrosis (EXPN), as determined on contrast-enhanced CT (CECT). Patients with EXPN are thought to have a better clinical outcome, although robust data are lacking. METHODS: A post hoc analysis was performed of a prospective multicentre database including 639 patients with necrotising pancreatitis on contrast-enhanced CT. All CECT scans were reviewed by a single radiologist blinded to the clinical outcome. Patients with EXPN were compared with patients with pancreatic parenchymal necrosis (with or without extrapancreatic necrosis). Outcomes were persistent organ failure, need for intervention and mortality. A predefined subgroup analysis was performed on patients who developed infected necrosis. RESULTS: 315 patients with EXPN were compared with 324 patients with pancreatic parenchymal necrosis. Patients with EXPN less often suffered from complications: persistent organ failure (21% vs 45%, p<0.001), persistent multiple organ failure (15% vs 36%, p<0.001), infected necrosis (16% vs 47%, p<0.001), intervention (18% vs 57%, p<0.001) and mortality (9% vs 20%, p<0.001). When infection of extrapancreatic necrosis developed, outcomes between groups were equal (mortality with infected necrosis: EXPN 28% vs pancreatic necrosis 18%, p=0.16). CONCLUSION: EXPN causes fewer complications than pancreatic parenchymal necrosis. It should therefore be considered a separate entity in acute pancreatitis. Outcome in cases of infected necrosis is similar. PMID- 22773552 TI - Constructing the moral body: self-care among older adults with multiple chronic conditions. AB - Older adults are increasingly living with and managing multiple chronic conditions. The self-management of illness occurs in a social and political context in which the responsibility for health has shifted from the State to the individual, who is expected to be an active consumer of health care. Although there has been extensive investigation of the management of single chronic conditions, the realities of living with multiple morbidities have largely been ignored, particularly among older adults. Addressing this gap, our study entailed in-depth interviews with 35 older Canadian adults, aged 73 to 91, who had between three and 14 chronic conditions. Self-care emerged as a primary means by which our participants managed their illnesses. Specifically, all of our participants were engaged in some form of self-care in order to cope with often debilitating physical symptoms and functional losses. They also utilized self-care because they had reached the limits of available medical treatment options. Finally, our participants argued that self-care was a moral responsibility that was underscored by gendered motivations. Whereas the men tended to emphasize the importance of self-care for the achievement of masculine ideals of control and invulnerability, the women suggested that self-care allowed them to maintain feminine norms of selflessness and sensitivity to the needs of others. In this way, self-care enabled the men and women to reframe their aging, chronically ill bodies as moral, socially valued bodies. We discuss our findings in relation to the extant research and theorizing pertaining to self-care, gender, and healthism. PMID- 22773553 TI - 'I was so done in that I just recognized it very plainly, "You need to do something"': Men's narratives of struggle, distress and turning to meditation. AB - Traditional masculinities can mean men are unable or unwilling to deal constructively with distress. However, researchers increasingly acknowledge that men and masculinities (including hegemonic styles) are diverse. Moreover, men can positively manage their well-being, although little research explores how they do so. Uniquely, our study sought to find men who report finding ways to care for themselves to examine narratives about how such self-care originated. We aimed to do this by exploring issues underpinning men's journeys towards meditation, focusing on implications for well-being. In-depth interviews were conducted in 2009 with 30 meditators, selected using principles of maximum variation sampling, and analysed with a modified 'constant comparison' approach. Men's journeys towards meditation were fraught with difficulties. Men described crossing a threshold from boyhood into 'manhood' where they encountered traditional forms of masculinity (e.g. stoicism), and most described subsequent strategies to disconnect from emotions. While men eventually found ways to engage more constructively with their emotions and well-being, this article explores the struggle and distress of their journeys. PMID- 22773551 TI - Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO-PK0104). AB - OBJECTIVE: AIO-PK0104 investigated two treatment strategies in advanced pancreatic cancer (PC): a reference sequence of gemcitabine/erlotinib followed by 2nd-line capecitabine was compared with a reverse experimental sequence of capecitabine/erlotinib followed by gemcitabine. METHODS: 281 patients with PC were randomly assigned to 1st-line treatment with either gemcitabine plus erlotinib or capecitabine plus erlotinib. In case of treatment failure (eg, disease progression or toxicity), patients were allocated to 2nd-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was time to treatment failure (TTF) after 1st- and 2nd-line therapy (TTF2; non inferiority design). KRAS exon 2 mutations were analysed in archival tumour tissue from 173 of the randomised patients. RESULTS: Of the 274 eligible patients, 43 had locally advanced and 231 had metastatic disease; 140 (51%) received 2nd-line chemotherapy. Median TTF2 was estimated with 4.2 months in both arms; median overall survival was 6.2 months with gemcitabine/erlotinib followed by capecitabine and 6.9 months with capecitabine/erlotinib followed by gemcitabine, respectively (HR 1.02, p=0.90). TTF for 1st-line therapy (TTF1) was significantly prolonged with gemcitabine/erlotinib compared to capecitabine/erlotinib (3.2 vs 2.2 months; HR 0.69, p=0.0034). Skin rash was associated with both TTF2 (rash grade 0/1/2-4:2.9/4.3/6.7 months, p<0.0001) and survival (3.4/7.0/9.6 months, p<0.0001). Each arm showed a safe and manageable toxicity profile during 1st- and 2nd-line therapy. A KRAS wild-type status (52/173 patients, 30%) was associated with an improved overall survival (HR 1.68, p=0.005). CONCLUSION: Both treatment strategies are feasible and demonstrated comparable efficacy; KRAS may serve as biomarker in patients with advanced PC treated with erlotinib. PMID- 22773554 TI - Brain-derived neurotrophic factor Val66Met polymorphism predicts worse functional outcome after surgery in patients with unruptured brain arteriovenous malformation. AB - BACKGROUND AND PURPOSE: The Val66Met polymorphism of brain-derived neurotrophic factor is associated with decreased brain-derived neurotrophic factor secretion and poor outcome after acute neurological injury. We hypothesized that the Met allele is associated with worsening of functional outcome after brain arteriovenous malformation resection. METHODS: Three hundred forty-one surgically treated patients with brain arteriovenous malformation with outcome data were genotyped for Val66Met. Outcome was change in modified Rankin Scale preoperatively versus postoperatively, dichotomized into poor (change >0) or good outcome (change <=0). Likelihood ratio tests for interactions and logistic regression analysis were performed. RESULTS: A significant interaction (P=0.03) of Val66Met genotype and hemorrhagic presentation existed; thus, ruptured and unruptured patients were considered separately. The Met allele was associated with increased risk of poor outcome among patients presenting unruptured (OR, 2.15; 95% CI, 1.02-4.55; P=0.045) but not ruptured (OR, 0.54; 95% CI, 0.19-1.53; P=0.25), adjusting for covariates. CONCLUSIONS: The Val66Met polymorphism is associated with worsened surgical outcome in patients with unruptured brain arteriovenous malformation, a group that currently has no good risk predictors. Further studies replicating these findings are needed. PMID- 22773555 TI - Warfarin-associated intracerebral hemorrhage is inadequately treated at community emergency departments. AB - BACKGROUND AND PURPOSE: The purpose of this study was to investigate time delays, adherence to guidelines, and their impact on outcomes in patients with warfarin associated intracerebral hemorrhage transferred from community emergency departments to a comprehensive stroke center. METHODS: We collected demographic, clinical, transfer time, treatment, and outcome data for patients transferred to our institution with warfarin-associated intracerebral hemorrhage from community emergency departments. RESULTS: Among 928 patients with intracerebral hemorrhage, 56 (6%) with warfarin-associated intracerebral hemorrhage (median international normalized ratio, 2.55) were transferred to the comprehensive stroke center. Twenty patients received no acute reversal therapy before transfer, only 4 of whom had international normalized ratios <=1.4 in the community emergency department. Median time of emergency department stay was 3.66 hours and median time to initiation of acute reversal therapy was 4.48 hours. Those who received >=3 U of fresh-frozen plasma or recombinant activated Factor VIIa (11 patients) before transfer had lower repeat international normalized ratios and better discharge dispositions than those treated less aggressively. CONCLUSIONS: Treatment of warfarin-associated intracerebral hemorrhage in community emergency departments is often suboptimal and does not adhere to published guidelines. Treating coagulopathy aggressively before interhospital transfer may improve outcomes and warrants further investigation. PMID- 22773556 TI - Physical therapists' guideline adherence on early mobilization and intensity of practice at dutch acute stroke units: a country-wide survey. AB - BACKGROUND AND PURPOSE: Clinical practice guidelines for patients with stroke recommend early stroke rehabilitation at acute hospital stroke units. The present study aimed to (1) explore the organization of early stroke rehabilitation; (2) investigate current practice with respect to early mobilization and augmented exercise therapy time; and (3) identify the perceived barriers to and facilitators for guideline adherence as reported by physical therapists (PTs) working on acute hospital stroke units. METHODS: All 96 Dutch acute hospital stroke units were requested to assign one PT for participation in the survey. RESULTS: Of the 96 contacted PTs, 91 returned the questionnaire. Seventy-one percent of acute hospital stroke units reported that out-of-bed mobilization of patients was performed within 24 hours. PTs provided a mean of 22 minutes of physical therapy per weekday and weekend therapy was not standard practice. PTs reported having sufficient knowledge of and experience with the clinical practice guidelines for patients with stroke and reported that the clinical practice guidelines for patients with stroke left enough room for them to draw their own conclusions and to take patient preferences into account. PTs perceived insufficient time to comply with the clinical practice guidelines for patients with stroke and a need for financial compensation to realize human resources. CONCLUSIONS: Our national survey among PTs suggests that the organization of early stroke rehabilitation varies considerably and that early mobilization and intensity of practice in early stroke rehabilitation are not optimal. Addressing this problem requires agreement between hospital management boards and insurance companies about minimum services and resources required and the introduction of novel methods of increasing duration of exercise therapy with minimal use of resources. PMID- 22773557 TI - Patients living in impoverished areas have more severe ischemic strokes. AB - BACKGROUND AND PURPOSE: Initial stroke severity is one of the strongest predictors of eventual stroke outcome. However, predictors of initial stroke severity have not been well-described within a population. We hypothesized that poorer patients would have a higher initial stroke severity on presentation to medical attention. METHODS: We identified all cases of hospital-ascertained ischemic stroke occurring in 2005 within a biracial population of 1.3 million. "Community" socioecomic status was determined for each patient based on the percentage below poverty in the census tract in which the patient resided. Linear regression was used to model the effect of socioeconomic status on stroke severity. Models were adjusted for race, gender, age, prestroke disability, and history of medical comorbidities. RESULTS: There were 1895 ischemic stroke events detected in 2005 included in this analysis; 22% were black, 52% were female, and the mean age was 71 years (range, 19-104). The median National Institutes of Health Stroke Scale was 3 (range, 0-40). The poorest community socioeconomic status was associated with a significantly increased initial National Institutes of Health Stroke Scale by 1.5 points (95% confidence interval, 0.5-2.6; P<0.001) compared with the richest category in the univariate analysis, which increased to 2.2 points after adjustment for demographics and comorbidities. CONCLUSIONS: We found that increasing community poverty was associated with worse stroke severity at presentation, independent of other known factors associated with stroke outcomes. Socioeconomic status may impact stroke severity via medication compliance, access to care, and cultural factors, or may be a proxy measure for undiagnosed disease states. PMID- 22773558 TI - Stratification of heterogeneous diffusion MRI ischemic lesion with kurtosis imaging: evaluation of mean diffusion and kurtosis MRI mismatch in an animal model of transient focal ischemia. AB - BACKGROUND AND PURPOSE: Ischemic tissue damage is heterogeneous, resulting in complex patterns in the widely used diffusion-weighted MRI. Our study examined the spatiotemporal characteristics of diffusion kurtosis imaging in an animal model of transient middle cerebral artery occlusion. METHODS: Adult male Wistar rats (N=18) were subjected to 90 minutes middle cerebral artery occlusion. Multiparametric MR images were obtained during middle cerebral artery occlusion and 20 minutes after reperfusion with diffusion-weighted MRI obtained using 8 b values from 250 to 3000 s/mm(2) in 6 diffusion gradient directions. Diffusion and kurtosis lesions were outlined in shuffled images by 2 investigators independently. T(2) MRI was obtained 24 hours after middle cerebral artery occlusion to evaluate stroke outcome. RESULTS: Mean diffusion lesion (23.5%+/ 8.1%, percentage of the brain slice) was significantly larger than mean kurtosis lesion (13.2%+/-2.0%) during middle cerebral artery occlusion. Mean diffusion lesion decreased significantly after reperfusion (13.8%+/-4.3%), whereas mean kurtosis lesion showed little change (13.0%+/-2.5%) with their lesion size difference being insignificant. CONCLUSIONS: We demonstrated that mean diffusion/mean kurtosis mismatch recovered reasonably well on reperfusion, whereas regions with concurrent mean diffusion and mean kurtosis deficits showed poor recovery. Diffusion kurtosis imaging may help stratify heterogeneous diffusion-weighted MRI lesions for enhanced characterization of ischemic tissue injury. PMID- 22773559 TI - Isoflurane attenuates blood-brain barrier disruption in ipsilateral hemisphere after subarachnoid hemorrhage in mice. AB - BACKGROUND AND PURPOSE: We examined effects of isoflurane, volatile anesthetics, on blood-brain barrier disruption in the endovascular perforation model of subarachnoid hemorrhage (SAH) in mice. METHODS: Animals were assigned to sham operated, SAH+vehicle-air, SAH+1%, or 2% isoflurane groups. Neurobehavioral function, brain water content, Evans blue dye extravasation, and Western blotting for sphingosine kinases, occludin, claudin-5, junctional adhesion molecule, and vascular endothelial cadherin were evaluated at 24 hours post-SAH. Effects of sphingosine kinase (N,N-dimethylsphingosine) or sphingosine-1-phosphate receptor 1/3 (S1P1/3) inhibitors (VPC23019) on isoflurane's action were also examined. RESULTS: SAH aggravated neurological scores, brain edema, and blood-brain barrier permeability, which were prevented by 2% but not 1% isoflurane posttreatment. Two percent isoflurane increased sphingosine kinase-1 expression and prevented a post SAH decrease in expressions of the blood-brain barrier-related proteins. Both N,N dimethylsphingosine and VPC23019 abolished the beneficial effects of isoflurane. CONCLUSIONS: Two percent isoflurane can suppress post-SAH blood-brain barrier disruption, which may be mediated by sphingosine kinase 1 expression and sphingosine-1-phosphate receptor-1/3 activation. PMID- 22773560 TI - Overcoming resistance to antiangiogenic therapies. AB - The concept of targeting new blood vessel formation, or angiogenesis, in tumors is an important advancement in cancer therapy, resulting, in part, from the development of such biologic agents as bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor (VEGF)-A. The rationale for antiangiogenic therapy is based on the hypothesis that if tumors are limited in their capacity to obtain a new blood supply, so too is their capacity for growth and metastasis. Additional evidence suggests that pruning and/or "normalization" of irregular tumor vasculature and reduction of hypoxia may facilitate greater access of cytotoxic chemotherapy (CT) to the tumor. Indeed, for metastatic colorectal cancer, bevacizumab in combination with established CT regimens has efficacy superior to that of CT alone. Despite ~2-month longer progression-free and overall survival times than with CT alone, patients still progress, possibly because of alternative angiogenic "escape" pathways that emerge independent of VEGF-A, or are driven by hypoxic stress on the tumor. Other VEGF family members may contribute to resistance, and many factors that contribute to the regulation of tumor angiogenesis function as part of a complex network, existing in different concentrations and spatiotemporal gradients and producing a wide range of biologic responses. Integrating these concepts into the design and evaluation of new antiangiogenic therapies may help overcome resistance mechanisms and allow for greater efficacy over longer treatment periods. PMID- 22773562 TI - Amino acid chloramine damage to proliferating cell nuclear antigen in mammalian cells. AB - Amino acid chloramines (AACLs) are reactive secondary products of activated neutrophils. To understand AACL damage in cell nuclei, we exploited proliferating cell nuclear antigen (PCNA) as a nuclear protein damage reporter, using western blotting and mass spectrometry. Chloramines of proline, arginine, and glycine caused significant damage to PCNA in cells. Chloramines of taurine and histidine caused slight damage to PCNA in cells. Other AACLs caused no PCNA damage in intact cells. Evidence supports a sulfonamide, sulfinamide, or sulfenamide crosslinking mechanism involving cysteine 148 at the PCNA subunit interface, methionine sulfoxide formation as the basis of electrophoretic mobility shifting, and tyrosine and/or methionine residues as the likely targets of AACL damage to the PCNA antibody epitope. An interstitial fluid model experiment showed that physiological amino acids can mediate HOCl damage to PCNA in the presence of proteins that would otherwise completely quench the HOCl. CONCLUSION: PCNA is a sensitive biomarker of AACL damage in cell nuclei. Arginine chloramine and proline chloramine, or reactive species derived from them, were shown to enter cells and damage PCNA. Amino acids were shown to have at least two different mechanisms for suppressing PCNA damage in cells by their corresponding AACLs. Cysteine 148 was shown to be essential for PCNA subunit crosslinking by AACLs, and a crosslinking mechanism was proposed. PMID- 22773563 TI - Review: The effect of insulin-like growth factor II in the regulation of tumour cell growth in vitro and tumourigenesis in vivo. AB - Insulin-like growth factor II (IGF-II) is a protein hormone that has been shown to exert several biological functions in mammals. IGF-II is produced mainly by the liver and to be systemically released to affect both the liver, in an autocrine and paracrine manner, as well as other tissues, through endocrine signaling. Nevertheless, it is also produced locally in various other tissues acting via autocrine and paracrine signalling. Research over the last decades has suggested that IGF-II also has a stimulatory effect on tumour cell growth but there are some notable exceptions to this rule. This conflicting view may have several explanations and hence current research has focused on gaining further insight into the transcriptional regulation and the metabolic pathways of IGF-II, which is hoped will result in greater understanding of the role of IGF-II in tumour development and new cancer therapies. This article aims at reviewing some of the key findings on how IGF-II affects tumour cells in vitro, as well as in vivo. PMID- 22773561 TI - Review: In vivo models for defining molecular subtypes of the primitive neuroectodermal tumor genome: current challenges and solutions. AB - Primitive neuroectodermal tumors (PNET) of the brain include medulloblastoma (MB) and central nervous system primitive neuroectodermal tumor (CNS PNET) subtypes, which share histological features yet differ at the genomic level and in clinical outcome. Delineation of the genetic anomalies between PNET subtypes is a current challenge for establishing effective targeted therapeutic strategies against these aggressive tumors. Current efforts have demonstrated that specific molecular pathways drive a subset of MB and CNS PNET, but the genetic basis for the deadliest forms of these tumors remains poorly understood and anecdotal. This is in part due to an overall lack of biologically relevant in vivo and in vitro model systems capable of direct comparison and identification of the genetic origins among PNET subtypes. Forward genetic, random mutagenesis in mice is an effective phenotype-driven method to model the genetic origins of human disease including cancer. We have applied this method to PNET by developing a single Sleeping Beauty transposon insertional mutagenesis mouse model that recapitulates the morphological similarities and genetic heterogeneity of MB and CNS PNET capable of identifying genetic drivers important for genesis of PNET. Importantly, this model has allowed new PNET phenotypes to be observed and is designed to reveal biologically relevant candidate oncogenes and tumor suppressor genes for MB and CNS PNET molecular subgroups in mice and humans. The ultimate goal of the approach we have taken is to uncover new understanding of the genetic basis for MB and CNS PNET development, how they are distinguished from each other, and offer potential targets for therapeutic testing to improve patient clinical outcome. PMID- 22773564 TI - Review: Exploring anticarcinogenic agents in a rat hepatocarcinogenesis model- focus on selenium and statins. AB - In this review, we describe a rat model for chemically induced hepatocarcinogenesis that can be used for studying the anticarcinogenic effects of different agents. In this model the process of carcinogenesis can be followed through the different stages of initiation, promotion and progression. Mechanistic studies of anticarcinogenic agents can be carried out and two examples are given by studies on selenium and statins as anticarcinogenic agents. These compounds suppress cancer via different mechanisms. In the case of selenium the induction of glutathione peroxidase 4 and inhibition of lipid peroxidation might be a part of the anticarcinogenic effect. In the case of statins, the inhibition of ubiquinone synthesis, as well as of the selenium-containing enzyme thioredoxin reductase 1 (TrxR1) might explain their anticarcinogenic properties. Interestingly, also in the case of selenium the inhibited carcinogenesis was associated with reduced TrxR activity, indicating an important role for this enzyme in carcinogenesis. PMID- 22773565 TI - A comprehensive procedural approach to genotyping KRAS and BRAF from paraffin embedded tissues for diagnostic purposes. AB - BACKGROUND: Mutations in the Kirsten Ras 1 (KRAS) and V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) genes may be predictive of response to drugs directly linked to the Epidermal Growth Factor Receptor (EGFR) signaling pathway. MATERIALS AND METHODS: A total of 230 samples from patients with metastatic colorectal cancer were analyzed for KRAS exon 1 and 2 and for BRAF exon 15 mutations. DNA from paraffin-embedded tumor sections was analyzed using microdissection, direct sequencing analysis and allelic separation by cloning. RESULTS: KRAS mutations were present in 44.3% of the tumor samples. The mutation frequency at hot-spot codons of exon 1 was 84.2%, whereas non-canonical variants had a frequency of 11.8%. Approximately 4% of the cases exhibited concomitant variations. BRAF mutations were present in 3.9% of the tumor samples. CONCLUSION: Our experience suggests that sequential microdissection, direct sequencing and allelic separation by cloning may improve the approach to mutational analysis of KRAS and BRAF in patients with colorectal cancer. PMID- 22773566 TI - Selenite enhances and prolongs the efficacy of cisplatin treatment of human ovarian tumor xenografts. AB - BACKGROUND/AIM: Our earlier studies on ovarian tumor xenografts provide evidence that co-treatment with selenite prevents the development of resistance to single treatment using the drug cisplatin. However, these studies did not reflect the repetitive schedule of clinical chemotherapy. We hypothesized that selenite can enhance the effectiveness of cisplatin during the course of repeated treatments, reflecting clinical practices. MATERIALS AND METHODS: Multiple i.p. injections of cisplatin (5.2 mg/kg) alone, or with selenite (1.5 mg/kg), were administered to mice bearing subcutaneous xenografts of human ovarian tumor (A2780) cells and the tumor volume was recorded. RESULTS: Selenite increased and prolonged the efficacy of multiple cisplatin treatments, although selenite was not an effective inhibitor by itself. In the absence of selenite, the effectiveness of cisplatin decreased. CONCLUSION: The ability of selenite to prolong the effectiveness of repetitive cisplatin treatment, most likely by preventing the development of resistance, makes it a strong candidate for inclusion in clinical trials. PMID- 22773567 TI - Expanded effector memory T-lymphocytes in DBA/2 mice do not inhibit the growth of SL2 tumours. AB - BACKGROUND: The aim of this study was to analyse changes in levels of memory T lymphocytes during growth of SL2 tumours in DBA/2 mice and to evaluate whether these lymphocytes may have an inhibitory effect on tumour growth. MATERIALS AND METHODS: Percentages of naive (CD8+CD44lowCD62L+), central memory (CD8+CD44high CD62L+) and effector memory (CD8+CD44highCD62L-) lymphocytes in the CD8+ subset in peripheral blood, spleen and lymph nodes of tumour-bearing and control mice were analysed by flow cytometry. RESULTS: The percentage of effector memory lymphocytes in the CD8+ subset increased during growth of tumours, whereas that of naive CD8+ lymphocytes decreased. No correlation between the levels of effector memory lymphocytes in peripheral blood and the mass of tumours was found. CONCLUSION: SL2 tumours induce expansion of effector memory lymphocytes in DBA/2 mice. However, expanded effector memory lymphocytes do not inhibit the growth of tumours. PMID- 22773568 TI - Experimental murine model of primary high grade undifferentiated pleomorphic sarcoma not otherwise specified. AB - BACKGROUND: Undifferentiated pleomorphic sarcoma not otherwise specified (NOS) is a malignant neoplasm of uncertain origin arising both in the soft tissue and the bone. The WHO classified this tumour in 2002 but controversy has plagued this entity due to limited availability of tissue for study. The aim of this study was to establish a reproducible xenograft model of primary human undifferentiated pleomorphic sarcoma NOS. MATERIALS AND METHODS: Primary human sarcoma samples were divided into tumour fragments and transplanted subcutaneously in mice. Sarcoma xenografts were analysed histolomorphologically (light/electron microscopy; immunohistochemistry). RESULTS: All tumours resulted in viable sarcoma NOS xenografts demonstrating similar histological patterns. In both the original tumours and the xenografts, tumour necrosis was found ranging from 15% to 25%. The background stroma of the xenografts was hyalinised like the primary sarcoma. Electron microscopical analyses showed good maintenance of ultrastructure. CONCLUSION: Implantation of intact tumor fragments yielded in a complete tumor take rate. The development of new cancer therapeutics requires animal models that closely resemble the human patient. This study provides ideal animal models for the research of pathogenesis and pathobiology of primary human undifferentiated pleomorphic sarcoma NOS. PMID- 22773569 TI - Tumor-educated macrophages promote tumor growth and peritoneal metastasis in an orthotopic nude mouse model of human pancreatic cancer. AB - BACKGROUND: Macrophages promote tumor growth by stimulating tumor-associated angiogenesis, cancer-cell invasion, migration, intravasation, and suppression of antitumor immune responses. MATERIALS AND METHODS: Ten transgenic nude mice, ubiquitously expressing green fluorescent protein (GFP), were injected subcutaneously with the human pancreatic cancer cell line, BXPC3, stably expressing red fluorescent protein (RFP). GFP-expressing macrophages from the GFP mice with the subcutaneous BxPC3-RFP tumor were harvested and defined as "tumor educated macrophages". Macrophages were also harvested from transgenic GFP mice (n=10) without tumors and identified as "naive macrophages." The tumor-educated and naive macrophages were then implanted into BxPC-3-RFP tumor-bearing non transgenic nude mice and compared for their ability to enhance tumor progression. RESULTS: In the control group, without macrophage injection, the average primary tumor weighed 668 mg and only three mice (30%) developed peritoneal metastases, which averaged 72 mg. The naive-macrophage group had an average tumor weight of 823 mg (p=0.51) and 50% developed peritoneal metastases, whose weight averaged 975 mg (p=0.029). The group treated with tumor-educated macrophages had an average primary tumor weight of 2095 mg (p=0.001) and 75% of mice developed peritoneal metastases, whose weight averaged 2135 mg (p=0.008). CONCLUSION: These results suggest that macrophages influence tumors, and tumors influence macrophages, and tumor-educated promote tumor progression. Tumor-educated macrophages may be a target for therapy of metastatic cancer. PMID- 22773571 TI - The effect of automated blood sampling on corticosterone levels, body weight and daily food intake in permanently catheterized male BALB/c mice. AB - BACKGROUND/AIM: Automated blood sampling has the benefit of sampling without human intervention, thus minimizing the associated stress response. Since this technique has not been thoroughly investigated in mice, the present study was designed to evaluate this technology in mice. MATERIALS AND METHODS: Male catheterized BALB/c mice were subjected to automated blood sampling, fecal sampling and daily recording of body weight and food intake for three days post surgery. Corticosterone levels in blood and feces were investigated as biomarkers of stress. RESULTS: Plasma corticosterone levels were elevated, and the circadian rhythm was disrupted as reflected in both plasma and feces. The body weight and daily food intake declined for the first two days post-surgery and increased at day three. DISCUSSION: These results demonstrate that surgery and subsequent automated blood sampling induce a stress response for up to three days post surgery, and it is concluded that further refinement of this technique is essential. PMID- 22773570 TI - Urokinase plasminogen activator, uPAR, MMP-2, and MMP-9 in the C6-glioblastoma rat model. AB - BACKGROUND: In glioblastoma multiforme (GBM), the serine protease urokinase plasminogen activator (uPA), and matrix metalloproteases (MMP-2/MMP-9) contribute to its invasive growth pattern, which is the major obstacle to successful surgical treatment. MATERIALS AND METHODS: The expression of uPA was determined in monolayers and spheroids of the rodent GBM cell line C6 by immunohistochemistry and polymerase chain reaction (PCR). The longitudinal expression of proteases was studied in orthotopically implanted spheroids by semi quantitative immunohistochemistry (IHC) in Sprague Dawley rats (n=40). The tumor volume was monitored by magnetic resonance imaging (MRI). RESULTS: In vitro, the GBM cell line C6 expresses high levels of uPA. In vivo, a continuous increase of uPA, uPA-receptor (uPAR), MMP-2, and MMP-9 expression was found in the infiltration zone. uPA was located exclusively in the infiltration zone and in the vascular basal layers. The mean tumor volume 23 days after implantation was 3.2 mm3. CONCLUSION: uPA, uPAR, MMP-2 and MMP-9 play an important role in GBM growth. Blockade of uPA and interruption of the proteolytic cascade could become a useful tool in the therapy of GBM. PMID- 22773572 TI - Positron-emission tomography (PET) imaging agents for diagnosis of human prostate cancer: agonist vs. antagonist ligands. AB - AIM: The present study adds scientific support to the growing debate regarding the superiority of radiolabeled bombesin-based antagonist peptides over agonists for molecular imaging and therapy of human tumors overexpressing the gastrin releasing peptide receptor (GRPR) and describes a detailed in vitro and in vivo comparison of 64Cu-NODAGA-6-Ahx-BBN(7-14)NH2 agonist and 64Cu-NODAGA-6-Ahx-DPhe6 BBN(6-13)NHEt antagonist ligands. MATERIALS AND METHODS: Conjugates were synthesized by solid-phase peptide synthesis, purified by reversed-phase high performance liquid chromatography, and characterized by electrospray ionization mass spectroscopy. The conjugates were radiolabeled with 64Cu. RESULTS: In vitro and in vivo data support the hypothesis for targeting of the GRPR by these tracer molecules. Maximum-intensity micro Positron Emission Tomography (microPET) imaging studies show the agonist ligand to provide high-quality, high-contrast images with very impressive tumor uptake and background clearance, with virtually no residual gastrointestinal or renal-urinary radioactivity. CONCLUSION: Based on microPET imaging experiments, we conclude the agonist peptide ligand to be a superior molecular imaging agent for targeting GRPR. PMID- 22773573 TI - The challenge of tumor heterogeneity--different phenotypes of cancer stem cells in a head and neck squamous cell carcinoma xenograft mouse model. AB - BACKGROUND/AIM: Besides late diagnosis, tumor metastasis and cancer relapse are the main reasons for the poor prognosis of patients with head and neck cancer. Several investigations have shown that tumor is of heterogeneous molecularity consisting of several subpopulations, with a broad range of biological behaviors. The ability and potential of tumor to infiltrate into vessels and into neighbouring organs, as well as the resistance to chemotherapeutical cancer therapy may be caused by cancer stem cells (CSCs). The aim of the present study was to illuminate the role and behaviour of (CD44) and (ALDH1A1) as tumor stem cell markers in a xenograft mouse model of squamous cell carcinoma. MATERIALS AND METHODS: Five female NMRI-Foxn1nu mice were injected with five million Detroit 562 cells (100 MUl). After sacrifice of the mice, tumors were excised. Then ALDH1A1, CD44, (EGFR), CD31 and Ki 67 were detected as molecular markers for tumor stem cells by immunohistopathology and immunofluorescence. RESULTS: The amount of putative CSC marker proteins CD44 and ALDH1A1 vary. ALDH1A1high tumor cells express low levels of CD44 and EGFR. The CD44+high expressers also exhibit expression of high levels of the EGFR. CSCs must be sub-classified depending on their expression of marker proteins. CONCLUSION: We assume that CSCs can also be sub-classified into migratory and stationary CSCs. ALDH1A1high/CD44low/EGFRlow tumor cells may be stationary and quiescent, whereas ALDH1A1-/CD44high/EGFRhigh expressers have a migratory, invasive nature. It is likely that a regulatory mechanism, as yet unknown, controls this conversion, from quiescent to active cancer stem cells. PMID- 22773574 TI - Review: Fluorescent protein-based tumor models. AB - Numerous animal models have been developed to provide a deeper insight to tumor progression in the search for new therapeutic leverage. The closer the tumor model represents the real tumor disease, the better. The ideal model provides monitoring, tumor cell detection and quantification, and the physiological events involved in tumor progression and tumor dissemination, simultaneously. Sensitive techniques have been developed which involve fluorescent protein-based methods, developed in order to quantify the tumor cells in a whole organ, and in parallel, to visualize the cells. These genetically encoded fluorescent proteins may also be used to develop biological sensors to monitor the physiological reaction of tumor cells within whole organs in living animals. Here, we aim to review past and present work and to show the perspectives of animal models involving fluorescent protein-transfected tumor cells. PMID- 22773575 TI - Antitumor protection by NGcGM3/VSSP vaccine against transfected B16 mouse melanoma cells overexpressing N-glycolylated gangliosides. AB - BACKGROUND: Cancer vaccines are designed to modulate immunological responses against tumor cells through the presentation of tumor antigens. MATERIALS AND METHODS: The mouse mRNA of the cytidine monophospho-N-acetylneuraminic acid hydroxylase (Cmah) gene, the enzyme that catalyzes the synthesis of N glycolylneuraminic acid (NGc), was cloned and transfected into the B16 melanoma cell line. Transfected cells (B16-H) were characterized and used as an NGcGM3 positive primary tumor model for the evaluation of the therapeutic activity of the NGcGM3/VSSP vaccine. RESULTS: The presence of NGcGM3 in B16-H cells promoted proliferation and adhesion in vitro, but resulted in reduced tumorigenicity in vivo. However, B16-H cells developed growing tumors in mice where NGcGM3/VSSP vaccination induced a therapeutic antitumor activity. NGcGM3/VSSP was ineffective in mice inoculated with parental B16 or B16-H cells that had lost NGcGM3 expression. CONCLUSION: The presence of NGcGM3 in tumor cells is critical for the antitumor activity of NGcGM3/VSSP vaccine. PMID- 22773576 TI - Imaging EGFR phosphorylation in intact human pancreatic carcinoma cells. AB - BACKGROUND/AIM: Carcinoma of the pancreatic duct is a highly malignant tumor characterized by aggressive and early metastastatic growth. A high rate of tumor recurrence after surgical resection and the lack of effective chemotherapeutic approaches result in low 5-year survival rates. Overexpression of epidermal growth factor (EGF) and its receptor have been correlated to a higher tumor biological aggressiveness. MATERIALS AND METHODS: We investigated EGFR RNA and protein expressions in different pancreatic carcinoma cell lines. EGFR phosphorylation was determined using acceptor photobleaching fluorescence resonance energy transfer (FRET). RESULTS: The imaging method allowed determination of receptor phorphorylation in intact cells without external calibration. Significant differences between the cell lines were found in EGFR expression but not in phosphorylation of EGFR without EGF stimulation. After stimulation with EGF, significant differences were found in receptor phorphorylation. EGFR expression did not correlate with EGFR phorphorylation. CONCLUSION: Since EGFR phosphorylation conveys signal transduction within cells, this molecular imaging method could be useful for the identification of patients with a high level of EGFR phosphorylation within tumor cells and, thus, to select patients for an EGFR-targeted therapy. PMID- 22773577 TI - Review: Mouse models of inflammatory bowel disease--insights into the mechanisms of inflammation-associated colorectal cancer. AB - The association between chronic inflammation and cancer has been noted for at least a century but the exact molecular mechanisms of cancer initiation and promotion by such inflammation are still poorly understood. The gastrointestinal tract is a unique organ where maintaining a balance between the colonic epithelial cells, the immune system and a fine-tuned response to the resident microflora is crucial for preserving the gut homeostasis. A breakdown of the tight interdependent regulation of the epithelium-immunity-microbiota triangle leads to inflammatory bowel disorders and may promote cancer. This review focuses on inflammation-associated colorectal cancer in mouse models of the disease and highlights emerging research trends. PMID- 22773579 TI - Protection against copper-induced cytotoxicity by inclusion of gold. AB - BACKGROUND: We previously reported that contact with copper (Cu) induced immediate cell death via an oxidation-involved mechanism, and the Cu-induced oxidation and cell death were effectively alleviated under hypoxic conditions. In order to explore alternative strategies for the protection from the Cu-induced cytotoxicity, we investigated whether the inclusion of gold (Au) in the Cu plate, as alloy,has a protective effect. MATERIALS AND METHODS: Human gingival fibroblast (HGF) cells, established from periodontal tissues, were inoculated on Au/Cu alloy of different Au ratios. After incubation at 37 degrees C for different times under normoxic conditions, cellular viability and amino acid consumption were determined. Changes in the elemental composition of the alloy and in the culture medium were chemically analyzed by X-ray photoelectron spectroscopy and by inductively coupled plasma-optical emission spectrometry. RESULTS: Contact with the Cu plate induced cytotoxicity and cystine oxidation in time-dependent manners. Inclusion of Au at more than 10% in the alloy, completely abrogated the cytotoxicity and reduced the oxidation of Cu and the elution of Cu from the alloy. CONCLUSION: Inclusion of Au as a component of alloy reduces the cytotoxicity of the Cu plate, possibly by reducing its oxidation. PMID- 22773578 TI - Review: In vivo models for measuring placental glutatione-S-transferase (GST-P 7 7) levels: a suitable biomarker for understanding cancer pathogenesis. AB - The Glutatione-S-transferases (GSTs) comprise a family of enzymes closely associated with the cell detoxification of xenobiotics. GSTs exist as homo- or heterodimers and have been grouped into at least seven distinct classes. The main function of GSTs is to catalyze the conjugation of reduced glutathione (GSH) to an electrophilic site of a broad range of potentially toxic and carcinogenic compounds, thereby making such compounds less dangerous and enabling their ready excretion. Placental GST, known as GST-P 7-7, is the main isoform found in normal placental tissue and comprises 67% of the total GST concentration in this tissue. During development, GST-P 7-7 decreases in concentration and is absent in adult tissues. Interestingly, GST-P 7-7 expression has been detected in adult tissues after exposure to carcinogenic agents in several experimental test systems, being considered a reliable biomarker of exposure and susceptibility in early phases of carcinogenesis. In this article, we review a series of studies involving GST-P 7 7 expression as a suitable tool for understanding cancer pathogenesis, especially cancer risk. PMID- 22773580 TI - Effect of three fluoride compounds on the growth of oral normal and tumor cells. AB - AIM: Comparative study of the growth inhibition by different types of fluoride compounds used in dentistry has been limited. We investigated the effects of sodium fluoride (NaF), diammine silver fluoride [Ag(NH3)2F] and 5-fluorouracil (5 FU) on the growth of eleven human normal and tumor cells in total. MATERIALS AND METHODS: Viable cell number was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Apoptosis induction was evaluated by caspase-3 activation and DNA fragmentation. Fluoride was determined using a fluoride-specific electrode. RESULTS: All compounds had little or no growth stimulating effect (hormesis) on all cells. Ag(NH3)2F exhibited the highest cytotoxicity towards both normal and tumor cells. 5-FU had the selective cytostatic activity towards oral squamous cell carcinoma cell lines, whereas NaF was selectively cytotoxic towards glioblastoma cell lines. None of the compounds induced internucleosomal DNA fragmentation and only 5-FU induced slight activation of caspase-3 in an oral squamous cell carcinoma cell line (HSC-2). Cytotoxicity of fluoride compounds was not reduced by superoxide dismutase and catalase, reducing the possibility of the involvement of reactive oxygen species in the mechanism of action. Approximately 0.01-0.09% initially added NaF was recovered from the cells, whereas the cellular uptake of Ag(NH3)2F and 5-FU was below the detection limit. CONCLUSION: Cytotoxicity of fluoride compounds may not be directly linked to their tumor specificity nor to their apoptosis-inducing activity. PMID- 22773581 TI - Chrysin, a natural and biologically active flavonoid, influences a murine leukemia model in vivo through enhancing populations of T-and B-cells, and promoting macrophage phagocytosis and NK cell cytotoxicity. AB - Chrysin (5,7-dihydroxyflavone), a natural and biologically active flavonoid found in plants, possesses many biological activities and anticancer effects. However, there is no available evidence regarding the antileukemia responses to chrysin in a mouse model. We hypothesized that chrysin affects murine WEHI-3 leukemia cells in vitro and in vivo. The present study showed that chrysin at concentrations of 5-50 MUM reduced the cell viability in concentration- and time-dependent manners. In an in vivo study, WEHI-3 leukemic BALB/c mice were established in order to determine antileukemia activity of chrysin. Our results revealed that chrysin increased the percentage of CD3 (T-cell maker), CD19 (B-cell maker) and Mac-3 (macrophages) cell surface markers in treated mice as compared with the untreated leukemia group. However, chrysin did not significantly influence the level of CD11b (a monocyte maker) in treated mice. Moreover, there was a significant increase in phagocytosis by macrophages from peripheral blood mononuclear cells, but no effect in those from the peritoneal cavity in leukemic mice after chrysin treatment. Isolated splenocytes from chrysin-treated leukemic mice demonstrated an increase of natural killer (NK) cell cytotoxicity. Based on these observations, chrysin might exhibit antileukemia effects on a murine WEHI-3 cell line-induced leukemia in vivo. PMID- 22773582 TI - Sorafenib inhibits TPA-induced MMP-9 and VEGF expression via suppression of ERK/NF-kappaB pathway in hepatocellular carcinoma cells. AB - Invasion by hepatocellular carcinoma (HCC) has been reported to occur via the up regulation of nuclear factor-kappaB (NF-kappaB). Sorafenib can improve the overall survival in patients with HCC, however, the association of its inhibitory mechanisms with the inactivation of NF-kappaB remains unclear. Here, Huh7 cell line transfected with NF-kappaB-luc2 vector was used to study the effects of sorafenib on NF-kappaB activity, on expressions of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF), which were induced by 12-O tetradecanoylphorbol-13-acetate (TPA). TPA increased the NF-kappaB activity and the expressions of MMP-9 and VEGF significantly, but its effects were suppressed by sorafenib in a dose-dependent manner. Similar results were found with PD98059, an inhibitor of extracellular signal-regulated kinase (ERK). Furthermore, transfection of Huh7 cell with an inhibitor of kappaB-alpha mutant vector, led to reduced TPA-induced MMP-9 and VEGF mRNA expressions. Sorafenib inhibits TPA induced MMP-9 and VEGF expressions via the suppression of ERK/NF-kappaB pathway in HCC cells. PMID- 22773583 TI - Immediately preoperative use of biological therapy does not influence liver regeneration after large resection--porcine experimental model with monoclonal antibody against epidermal growth factor. AB - BACKGROUND: The aim of this work was to study the influence of isolated biological therapy administered immediately before extended liver resection on liver function and regenerative capacity of future liver remnant (FLR) in a large animal experiment. MATERIALS AND METHODS: Nineteen piglets were included in this study (10 in the control group and 9 in the experimental group). A port-a-cath was introduced into the superior caval vein. On days 11 and 4 before liver resection, cetuximab was administered via this port at 400 mg/m2 of piglet body surface. Physiological solution was applied to the control group. Resection of the left lateral, left medial and right medial hepatic lobes was followingly performed (reduction of 50-60% of liver parenchyma). Blood samples were collected at different times before the operation and after liver resection. Serum levels of bilirubin, urea, creatinine, alkaline phosphatase, gamma glutamyltransferase, cholinesterase, aspartate aminotransferase, alanine aminotransferase, albumin, C reactive protein and transforming growth factor-beta1 were assessed. The ultrasonographic examinations at different time points were performed pre operatively and after liver resection in order to assess the liver volume. The biopsies from the liver parenchyma were examined for proliferative activity, binocluated hepatocytes, size of hepatocytes, and the length of the lobuli. The comparison of distribution of the studied parameters between the groups was carried out using the Wilcoxon test. The Spearman rank correlation co-efficient was used because of the non-Gaussian distribution of the parameter values. The whole development of the studied parameters over time was compared between the groups using ANOVA. RESULTS: There were no important complications of administration of biologic therapy during the operation or throughout the peri operative period. There was no statistically significant difference in the regeneration of FLR nor were any differences in biochemical, immunoanalytical and histological parameters detected. CONCLUSION: The achieved results of comparable liver regeneration in both the experimental and control groups confirms the use of biological treatment with cetuximab in the pre-operative period for minimizing the recovery period. PMID- 22773584 TI - Metallothionein colon crypt immuno-positivity as a rapid in vivo essay for drug efficacy studies. AB - Metallothionein immune positivity indices are considered as representative of crypt stem cell mutations. The frequency and size of MT- immunopositive foci, as well as the total number of MT-immunopositive crypts were assessed here in a short term in vivo assay. Drug efficacy was tested on early mutated crypts in colon of Balb-c mice 30 days after induction with a single dose of the mutagen dimethylhydrazine. The different drugs used (MS 275, vioxx, 5-fluorouracil, aminophylline, 5-azadeoxycytine) affected the metallothionein - immunopositive crypt frequency according to their predicted efficacy on this specific model of mouse colon carcinogenesis. This preliminary validation study of metallothionein immunopositive crypt frequency strengthens the evidence that metallothionein immunopositivity indices could be used as short-term markers to assess the capability of different pro-drugs to counteract crypt invasion and clonal expansion of mutated stem cell progeny. This rapid in vivo test (30 days) based on metallothionein immunopositivity indices can be assayed in paraffin-fixed tissue sections and has been validated against the Glucose 6 phosphate Dehydrogenase assay. To quantify metallothionein immunopositivity indices, we devised a novel fast analysis protocol based on the Zeiss Axiovision software for image processing. PMID- 22773585 TI - Bone healing effects of diode laser (808 nm) on a rat tibial fracture model. AB - Low level laser therapies (LLLT) have analgesic, vasodilatory and anti inflammatory effects. The present study investigated the effects of LLLT with a diode laser (808 nm) device on the healing of the rat tibial fracture. Forty eight, 8-week-old, male Sprague-Dawley rats were used for this study. After creating the tibial fracture model, the animals were randomly divided into laser and control groups. The animals were euthanized for histopathological and radiological evaluation. The biomechanical strength of the fractures was evaluated using a bending test. The histopathological and radiological evaluations suggested that the laser group developed new bone formations much earlier than those of the control group. The maximum tolerance force of the laser group was significantly higher than that of the control group (p<0.05). These findings suggest positive effects of LLLT in accelerating the bone healing process, especially in the early stage of bone formation. PMID- 22773586 TI - CXCR4/SDF-1alpha-mediated chemotaxis in an in vivo model of metastatic esophageal carcinoma. AB - BACKGROUND/AIM: The chemokine receptor CXCR4 and its ligand (stromal cell-derived factor-1alpha; SDF-1alpha) play an important role in tumor cell chemotaxis and metastatic homing of esophageal carcinoma. Several methods are available to examine tumor cell migration in vitro. However, in vivo chemotaxis is subject to complex tumor-host interactions. The aim of this study was to establish an in vivo model of chemotaxis for esophageal carcinoma that allows the examination of tumor cell migration and metastatic homing in the complex microenvironment. MATERIALS AND METHODS: CXCR4 expression of OE19 adenocarcinoma cells was determined by immunostaining in an orthotopic esophageal model. SDF-1alpha mediated migration of cells was examined in vitro. An in vivo model of chemotaxis and metastasis was established by subcutaneous injection of OE19 cells into NMRI/nu mice and by daily stimulation with SDF-1alpha. RESULTS: CXCR4 is expressed in the primary tumor and in the metastatic tissue. CXCR4-positive OE19 cells are susceptible to SDF-1alpha-mediated migration. The novel in vivo model leads to developement of metastases in liver, lung, peritoneum and retroperitoneum after stimulation with SDF-1alpha but not with PBS, and revealed an SDF-1alpha dose-dependent migratory effect. CONCLUSION: As metastasis is still the leading cause of tumor-related death, it is essential to investigate the complex tumor-host interactions involved in metastatic homing. We established an in vivo model of chemotaxis and metastasis for esophageal carcinoma, which allows investigation and inhibition of CXCR4/SDF-1alpha-mediated cell survival and proliferation, chemotaxis and homing, adhesion, and tumor angiogenesis. PMID- 22773587 TI - Changes of blood fluidity in the early hepatopathy in rats. AB - The present study was designed to examine the influence of the early stage hepatopathy on blood fluidity by using a rat experimental system. F344 male rats, 4 weeks of age, were fed chow containing 3'-methyl-4-dimethylaminoazobenzene (DAB) at 0.06%. These rats were autopsied 8, 12, 16 and 20 weeks after starting DAB feeding. Blood samples were collected from the inferior vena cava under pentobarbital anesthesia and blood fluidity and platelet aggregation activity were examined by a Micro Channel Array Flow Analyzer and a platelet aggregometer, respectively. We also examined histological changes in the liver after staining with hematoxylin-eosin. Histological observation of the liver revealed early stage hepathopathy when the organs were obtained from rats that fed DAB for more than 16 weeks. Although DAB-feeding of rats for 8 and 12 weeks barely affected blood fluidity, long-term intake (>16 weeks) caused decrease in fluidity. On the other hand, platelet aggregation activity was increased when rats were fed DAB for more than 16 weeks. The present results suggest that assaying for blood fluidity may be useful for the assessment of the degree of hepatopathy. PMID- 22773588 TI - Review: BBN as an urothelial carcinogen. AB - Experimental urinary bladder tumours have been proposed as a useful model for the study of urinary bladder carcinogenesis, as well as for evaluating new therapeutic strategies. Consequently, the administration of chemical carcinogens is one of the most commonly used methods for inducing urinary bladder tumours. N butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is, undoubtedly, the most-used urothelial chemical carcinogen. BBN belongs to the nitrosamine family, a wide group of alkylating agents that are able to induce bladder tumours in laboratory animals. Depending on the animal species, the spectrum of urothelial lesions induced by BBN varies, but is similar to those observed in humans. BBN has a high propensity to induce mutations affecting the expression of genes such as p53, RAS and H19 among others. The aim of this study was to review BBN as a urothelial tumour inducer, taking into consideration its chemical characteristics, properties and spectrum of lesions induced, as well as its possible applications. PMID- 22773593 TI - Hyperkalemia in predialysis patients. PMID- 22773590 TI - Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy. AB - BACKGROUND AND OBJECTIVES: The discovery of different podocyte autoantibodies in membranous nephropathy (MN) raises questions about their pathogenetic and clinical meaning. This study sought to define antibody isotypes and correlations; to compare levels in MN, other glomerulonephritides, and controls; and to determine their association with clinical outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Serum IgG(1), IgG(3), and IgG(4) against aldose reductase (AR), SOD2, and alpha-enolase (alphaENO) were measured at diagnosis in 186 consecutive MN patients, in 96 proteinuric controls (36 with FSGS, and 60 with IgA nephropathy), and in 92 healthy people recruited in four Italian nephrology units. Anti-phospholipase A2 receptor (PLA2r) and anti-neutral endopeptidase (NEP) IgG(4) were titrated in the same specimens. Association with 1-year follow-up clinical parameters was studied in 120 patients. RESULTS: IgG(4) was the most common isotype for all antibodies; IgG(1) and IgG(3) were nearly negligible. IgG(4) levels were positive in a significant proportion of MN patients (AR, 34%; SOD2, 28%; alphaENO, 43%). Antibody titers were higher in MN than in healthy and pathologic controls (P<0.005). Anti-NEP IgG(4) did not differ from normal controls (P=0.12). Anti-PLA2r IgG(4) was detected in 60% of patients and correlated with anti-AR, anti-SOD2, and anti-alphaENO IgG(4) (P<0.001). In MN patients negative for the whole antibody panel (20%), 1-year proteinuria was lower compared with patients with at least one antibody positivity (P<0.05). CONCLUSIONS: Our data suggest that IgG(4) is the prevalent isotype for antibodies against cytoplasmic antigens of podocytes (AR, SOD2, alphaENO). Their levels were higher than in other proteinuric glomerulonephritides and in normal controls and were correlated with anti-PLA2r. Only baseline negativity for all known antibodies predicted lower 1-year proteinuria. PMID- 22773594 TI - To dialyze or not: the patient with metastatic cancer and AKI in the intensive care unit. AB - AKI severe enough to necessitate renal replacement therapy occurs in approximately 5% of patients admitted to the intensive care unit (ICU) and is associated with in-hospital mortality in excess of 50%. Complicating factors, such as cancer, can increase in-hospital mortality to 85%. Intensivists often expect that consulted nephrologists will provide dialysis when asked to do so, without considering whether it is likely to benefit the patient and therefore is medically and ethically appropriate. In this Attending Rounds, on the basis of the evidence and recommendations in Shared Decision-Making in the Appropriate Initiation of and Withdrawal from Dialysis, a clinical practice guideline, a case of anuric AKI in the ICU is presented and analyzed. Woven into the discussion are insights from the clinical and ethics literature on this topic, along with the experience of the author. This Attending Rounds presents an approach to deciding when it is not appropriate to dialyze patients with AKI in the ICU. PMID- 22773591 TI - Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality. AB - BACKGROUND: Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. METHODS: This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. RESULTS: Administration of potassium citrate resulted in persisting normalization of S [HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. CONCLUSIONS: Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage. PMID- 22773596 TI - Televised entertainment-education to prevent adolescent alcohol use: perceived realism, enjoyment, and impact. AB - Alcohol use among adolescents is a concern in the Netherlands because of its high prevalence and risks. To discourage adolescents from drinking alcohol, a televised entertainment-education (E-E) intervention was developed. This study investigated responses of adolescents on perceived realism and enjoyment of the E E intervention, as well as its impact on alcohol drinking behavior. Viewers perceived the E-E narratives to be credible and enjoyable but did not relate to the characters in the narratives. However, exposure to the E-E intervention predicted desired changes in alcohol drinking behavior, intentions to decrease alcohol use, and perceived normative pressure, especially in less educated viewers. These findings demonstrate that E-E is a promising strategy to target adolescent alcohol use. Future research will focus on the individual processes and story elements that account for the positive results. PMID- 22773597 TI - Using active video games for physical activity promotion: a systematic review of the current state of research. AB - This systematic review evaluates interventions using active video games (AVGs) to increase physical activity and summarizes laboratory studies quantifying intensity of AVG play among children and adults. Databases (Cochrane Library, PsychInfo, PubMed, SPORTDiscus, Web of Science) and forward citation and reference list searches were used to identify peer-reviewed journal articles in English through March 2011. Studies that used off-the-shelf AVGs to increase physical activity with quantitative outcomes or studies that quantified intensity of AVG play were included. Information on sample characteristics, AVGs employed, study design and conditions, outcome measures, results, and conclusions was extracted by two researchers. Intervention studies were ranked on design quality. Thirteen interventions and 28 laboratory studies were identified. All laboratory studies demonstrated that AVGs are capable of providing light-to-moderate intensity physical activity. However, only three interventions supported AVGs as an effective tool to significantly increase physical activity or exercise attendance. As AVGs are becoming more popular, additional research is needed to determine how to capitalize on the potential of AVGs to increase physical activity. PMID- 22773598 TI - Perceptions about HIV and condoms and consistent condom use among male clients of commercial sex workers in the Philippines. AB - Because consistent condom use is an effective strategy in the prevention of sexually transmitted infections and HIV transmission, it is important to examine social cognitive influences of consistent condom use not only among female sex workers (FSWs) but also among their male clients, for whom less is known. Because little is known about how HIV knowledge and condom attitudes affect condom use among male clients of FSWs in the Philippines, the main objective was to determine what characteristics (age, education, HIV knowledge, marital status) as well as attributes taken from protection motivation theory (perceived vulnerability, perceived severity, response efficacy) are significantly associated with consistent condom use among male clients of FSWs. Logistic regression analyses showed that the odds of using condoms consistently with an FSW are 13% higher for those with more years of education (adjusted odds ratio [AOR] = 1.13; 95% confidence interval [CI] = 1.03, 1.23), higher versus lower perception of severity of HIV/AIDS (AOR = 1.97; 95% CI = 1.04, 3.73), and had a higher score for response efficacy of condoms (AOR = 1.14; 95% CI = 1.03, 1.27). Future HIV/AIDS prevention interventions that address condom use among male clients should promote educational attainment and focus on awareness of the enduring negative health consequences of acquiring HIV/AIDS, as well as cultivate positive attitudes toward the efficacy of condom use, using creative social marketing strategies. PMID- 22773599 TI - Moderators of youth exercise intention and behavior. AB - This study tested moderators of the theory of planned behavior (TPB) based on geographical region, gender, race, and income among adolescents in an exercise context using multigroup path analyses. Participants were eighth- and ninth-grade students from Louisiana (LA; N = 448, M age = 14.37 years) and Pennsylvania (PA; N = 681, M age = 14.28 years). They completed measures of intention, attitude, subjective norm, perceived behavioral control, and exercise behavior. Based on two path analyses, geographical region was a significant moderator (p < .001); therefore, the moderating effects of gender, race, and income were analyzed separately for each state. Gender was a significant moderator for LA (p < .001) but not for PA (p = .90). Race and income did not moderate the TPB relationships within each state. Findings support the moderating effect of geographical region on the TPB construct relationships and indicate that gender moderates the TPB construct relationships in LA youth. PMID- 22773600 TI - Survival for older patients with acute myeloid leukemia: a population-based study. AB - BACKGROUND: Acute myeloid leukemia is the second most common leukemia among United States adults with a median age of 69 years. We investigated recent clinical practices related to treatments and disease outcomes in older patients with acute myeloid leukemia in the United States. DESIGN AND METHODS: In this retrospective cohort study, we used Surveillance, Epidemiology, and End Results program data from 2000 through 2007 linked to Medicare enrollment and utilization data in the United States. RESULTS: Among 5,480 patients with acute myeloid leukemia (median age 78 years, range 65-93), 38.6% received leukemia therapy within three months of diagnosis (treated group). Practice changed with 16.3% of treated patients receiving hypomethylating agents after 2004 when those agents became available. Median survival was two months in the untreated group versus six months in the treated group (P<0.01) with the biggest improvements seen in those aged 65-69 years (10 months vs. 4 months; P<0.01) and 70-74 years (8 months vs. 3 months; P<0.01). In 46 patients receiving allogeneic hematopoietic cell transplantation (0.8%), the median survival from diagnosis was 22 months. CONCLUSIONS: Therapy for leukemia improves overall survival in older acute myeloid leukemia patients. Based on their comorbidities, most patients up to 80 years of age should be considered for treatment. New therapies including hypomethylating agents and allogeneic hematopoietic cell transplantation are promising and must be compared with other chemotherapy regimens. PMID- 22773601 TI - Effects of switching from a reduced dose imiglucerase to velaglucerase in type 1 Gaucher disease: clinical and biochemical outcomes. AB - This paper describes the effects of a switch to velaglucerase alfa in a group of adult patients with type 1 Gaucher disease, all of whom had previously had their dose reduced as a consequence of the worldwide imiglucerase shortage. Thirty-two patients from two large European Gaucher centers switched to treatment with velaglucerase alfa after 1-8.5 months of dose reduction. The course of important Gaucher disease parameters was studied at four time points: one year before the shortage, just before the shortage, before a switch to velaglucerase and after up to one year of treatment with velaglucerase. These parameters included hemoglobin concentration, platelet count, plasma chitotriosidase activity in all patients, and spleen and liver volumes (as well as bone marrow fat fraction images) in 10 patients. Decreases in platelet counts as a result of reduced treatment with imiglucerase were quickly restored on treatment with velaglucerase alfa. Chitotriosidase activity declined overall after switching. Five out of 10 patients had an increase in liver volume of at least 10% after six months of velaglucerase treatment, which was reversible in 3. Most patients received infusions at home and no important side effects were observed. Velaglucerase alfa appears to be a safe and effective alternative for imiglucerase. PMID- 22773602 TI - Atorvastatin reduces serum cholesterol and triglycerides with limited improvement in vascular function in adults with sickle cell anemia. PMID- 22773603 TI - Spliceosomal gene mutations are frequent events in the diverse mutational spectrum of chronic myelomonocytic leukemia but largely absent in juvenile myelomonocytic leukemia. AB - Chronic myelomonocytic leukemia is a heterogeneous disease with multifactorial molecular pathogenesis. Various recurrent somatic mutations have been detected alone or in combination in chronic myelomonocytic leukemia. Recently, recurrent mutations in spliceosomal genes have been discovered. We investigated the contribution of U2AF1, SRSF2 and SF3B1 mutations in the pathogenesis of chronic myelomonocytic leukemia and closely related diseases. We genotyped a cohort of patients with chronic myelomonocytic leukemia, secondary acute myeloid leukemia derived from chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia for somatic mutations in U2AF1, SRSF2, SF3B1 and in the other 12 most frequently affected genes in these conditions. Chromosomal abnormalities were assessed by nucleotide polymorphism array-based karyotyping. The presence of molecular lesions was correlated with clinical endpoints. Mutations in SRSF2, U2AF1 and SF3B1 were found in 32%, 13% and 6% of cases of chronic myelomonocytic leukemia, secondary acute myeloid leukemia derived from chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia, respectively. Spliceosomal genes were affected in various combinations with other mutations, including TET2, ASXL1, CBL, EZH2, RAS, IDH1/2, DNMT3A, TP53, UTX and RUNX1. Worse overall survival was associated with mutations in U2AF1 (P=0.047) and DNMT3A (P=0.015). RAS mutations had an impact on overall survival in secondary acute myeloid leukemia (P=0.0456). By comparison, our screening of juvenile myelomonocytic leukemia cases showed mutations in ASXL1 (4%), CBL (10%), and RAS (6%) but not in IDH1/2, TET2, EZH2, DNMT3A or the three spliceosomal genes. SRSF2 and U2AF1 along with TET2 (48%) and ASXL1 (38%) are frequently affected by somatic mutations in chronic myelomonocytic leukemia, quite distinctly from the profile seen in juvenile myelomonocytic leukemia. Our data also suggest that spliceosomal mutations are of ancestral origin. PMID- 22773604 TI - Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry. AB - Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8(+) T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes favoring both immune cytotoxicity and recovery of B-cell production and homing, suggesting improved immune surveillance. PMID- 22773605 TI - ALK-positive anaplastic large cell lymphoma limited to the skin: clinical, histopathological and molecular analysis of 6 pediatric cases. A report from the ALCL99 study. AB - Anaplastic large cell lymphomas are peripheral T-cell lymphomas that are characterized by a proliferation of large anaplastic blasts expressing CD30. In children, systemic anaplastic large cell lymphomas often present at advanced clinical stage and harbor translocations involving the anaplastic lymphoma kinase (ALK) gene leading to the expression of chimeric anaplastic lymphoma kinase (ALK) fusion proteins. Primary cutaneous anaplastic large cell lymphoma is regarded as an ALK-negative variant confined to the skin and is part of the spectrum of primary cutaneous CD30-positive T-cell lymphoproliferative disorders. Thirty three of 487 pediatric patients registered within the Anaplastic Large Cell Lymphoma-99 trial (1999 to 2006) presented with a skin limited CD30-positive lympho-proliferative disorder. In 23 of the 33 patients, material for international histopathological review was available, and the cases were studied for histopathological, immunophenotypical and clinical features as well as for breaks within the ALK gene. Five of 23 cases and one additional case (identified after closure of the trial) expressed ALK-protein. Complete staging excluded any other organ involvement in all children. Expression of ALK proteins was demonstrated by immunohistochemistry in all cases and the presence of breaks of the ALK gene was genetically confirmed in 5 evaluable cases. The histopathological and clinical picture of these skin-restricted ALK-positive lymphomas was indistinguishable from that of cutaneous anaplastic large cell lymphoma. Five children presented with a single skin lesion that was completely resected in 4 and incompletely resected in one. Three of these patients received no further therapy, 2 additional local radiotherapy, and one chemotherapy. All children remain in complete remission with a median follow up of seven years (range 1-8 years). We present 6 pediatric cases of ALK-positive primary cutaneous anaplastic large cell lymphomas. After thorough exclusion of systemic involvement, therapy confined to local measures seems to be sufficient to induce cure. PMID- 22773606 TI - Molecular pathogenesis of Waldenstrom's macroglobulinemia. AB - Waldenstrom's macroglobulinemia is an indolent, lymphoproliferative disease, characterized by a heterogeneous lymphoplasmacytic bone marrow infiltrate and high immunoglobulin M production. While technological advances over the past several decades have dramatically improved the possibilities of studying the molecular basis of Waldenstrom's macroglobulinemia, the pathogenesis of the disease remains fragmented. Undoubtedly, research has been successful in uncovering underlying aberrations and deregulated mechanisms in this disease, providing useful information for identifying biomarkers for disease diagnosis, risk stratification and therapeutic intervention, but there is still a long way to go before the pathogenesis of Waldenstrom's macroglobulinemia is fully revealed. In addition, the low number of in vitro or in vivo models significantly challenges extensive analysis. In this manuscript, we review the molecular basis of this disease. PMID- 22773608 TI - Maternal health care amid political unrest: the effect of armed conflict on antenatal care utilization in Nepal. AB - Armed conflicts, which primarily occur in low- and middle-income countries, have profound consequences for the health of affected populations, among them a decrease in the utilization of maternal health care services. The quantitative relationship between armed conflict and maternal health care utilization has received limited attention in the public health literature. We evaluate this relationship for a particular type of health care service, antenatal care, in Nepal. Using count regression techniques, household survey data and sub-national conflict data, we find a negative correlation between the number of antenatal care visits and incidents of conflict-related violence within a respondent's village development committee. Specifically, we find that under high-intensity conflict conditions women receive between 0.3 and 1.5 fewer antenatal care check ups. These findings imply that maternal health care utilization is partially determined by characteristics of the social environment (e.g. political instability) and suggest health care providers need to revise maternal health strategies in conflict-affected areas. Strategies may include decentralization of services, maintaining neutrality among factions, strengthening community-based health services and developing mobile clinics. PMID- 22773607 TI - CYBRD1 as a modifier gene that modulates iron phenotype in HFE p.C282Y homozygous patients. AB - BACKGROUND: Most patients with hereditary hemochromatosis in the Caucasian population are homozygous for the p.C282Y mutation in the HFE gene. The penetrance and expression of hereditary hemochromatosis differ largely among cases of homozygous p.C282Y. Genetic factors might be involved in addition to environmental factors. DESIGN AND METHODS: In the present study, we analyzed 50 candidate genes involved in iron metabolism and evaluated the association between 214 single nucleotide polymorphisms in these genes and three phenotypic outcomes of iron overload (serum ferritin, iron removed and transferrin saturation) in a large group of 296 p.C282Y homozygous Italians. Polymorphisms were tested for genetic association with each single outcome using linear regression models adjusted for age, sex and alcohol consumption. RESULTS: We found a series of 17 genetic variants located in different genes with possible additive effects on the studied outcomes. In order to evaluate whether the selected polymorphisms could provide a predictive signature for adverse phenotype, we re-evaluated data by dividing patients in two extreme phenotype classes based on the three phenotypic outcomes. We found that only a small improvement in prediction could be achieved by adding genetic information to clinical data. Among the selected polymorphisms, a significant association was observed between rs3806562, located in the 5'UTR of CYBRD1, and transferrin saturation. This variant belongs to the same haplotype block that contains the CYBRD1 polymorphism rs884409, found to be associated with serum ferritin in another population of p.C282Y homozygotes, and able to modulate promoter activity. A luciferase assay indicated that rs3806562 does not have a significant functional role, suggesting that it is a genetic marker linked to the putative genetic modifier rs884409. CONCLUSIONS: While our results support the hypothesis that polymorphisms in genes regulating iron metabolism may modulate penetrance of HFE-hereditary hemochromatosis, with emphasis on CYBRD1, they strengthen the notion that none of these polymorphisms alone is a major modifier of the phenotype of hereditary hemochromatosis. PMID- 22773609 TI - The impact of community-based, workshop activities in multiple local dialects on the vaccination coverage, sanitary living and the health status of multiethnic populations in Lao PDR. AB - Studies on effective community-based intervention in areas inhabited by multiple ethnic groups are limited. The present study was performed to evaluate the impact of workshop activities in multiple local dialects guided by lay facilitators on vaccination coverage, sanitary living and health status in a northern district of Lao PDR. In target villages, facilitators were selected and trained to assist at village meetings to discuss health issues and develop and implement action plans. Manuals and posters with graphics were distributed. Skills were taught through demonstrations by specialists. The vaccination coverage among children and women improved significantly after 1 year. Villagers started using toilets, collecting and burning garbage, and isolating animals from human dwellings, and these activities were continued in 76, 84 and 87% of villages, respectively, 5 years after the start of the activities. The frequency of villagers falling ill was reduced in 67% of the villages. After adjustment for sociocultural characteristics and ethnicity, both the continuous sanitary living index and the reduction in the frequency of villagers falling ill were associated with the higher levels of community participation in the workshop activities. The results demonstrated that the community-based workshop activities improved vaccination coverage, sanitary living and health status. Participatory group discussions in local dialects and village activities led by lay facilitators, supervision and consultation by district trainers who were well recognized by villagers, and the distribution of pictorial educational materials can be an effective and sustainable health promotion approaches among multiethnic groups in under resourced areas. PMID- 22773616 TI - From theory to practice: intervention fidelity in a randomized controlled trial aiming to optimize weight development during pregnancy. AB - BACKGROUND: Intervention fidelity is an increasingly important methodological concept in process evaluations. In this article, the authors investigated the intervention fidelity in a randomized controlled trial on excessive weight gain prevention in pregnancy. METHOD: A sample of 109 audiotaped counseling sessions, linked to 65 women in the intervention group of the New Life(style) trial, was drawn. The following criteria were quantitatively evaluated using a fidelity checklist: (a) reach, (b) dose, (c) adherence to study objectives, (d) adherence to underlying problem-solving treatment (PST) theory, and (e) counselor competence. RESULTS: A total of 60.4% received all counseling sessions. The dose of intervention components was generally moderate (50.9% to 60.4%), and the dose of PST components was low (17.3%). Adherence to study objectives was moderate (64.2%) and adherence to PST theory was low (43.2%). The counselors sufficiently stimulated the participant to optimize lifestyle (54.2% of the sessions), provided positive feedback (50.5%), and left the initiative regarding problem solving to the participant (71%). One of the two counselors performed significantly better on all measured criteria (p < .001). CONCLUSIONS: Intervention fidelity in the New Life(style) trial was generally low to moderate. In future interventions, it is recommended to put more emphasis on counselor recruitment, training, and intervention protocol contents. Fellow researchers are encouraged to embed a process evaluation into all study stages, taking into account all essential process elements, and to link process outcomes to more distal, health outcomes. PMID- 22773610 TI - Cardiac adaptation in athletes of black ethnicity: differentiating pathology from physiology. AB - Cardiac adaptation to intense physical exercise is determined by factors including age, gender, body size, sporting discipline and ethnicity. Differentiating physiology from pathological conditions such as hypertrophic cardiomyopathy (HCM) is challenging, but relevant, as HCM remains the commonest cause of sudden death in young athletes. Marked electrocardiographic repolarisation changes and echocardiographic left ventricular hypertrophy have been demonstrated in athletes of black ethnicity. Such changes highlight the overlap between 'athlete's heart' and morphologically mild HCM with potential for false-positive diagnoses and disqualification from competitive sport. The focus of this article is to provide practical considerations in differentiating physiological adaptation to exercise from cardiac pathology in athletes of black ethnicity. PMID- 22773617 TI - Evaluation of field triage decision scheme educational resources: audience research with emergency medical service personnel. AB - In an effort to encourage appropriate field triage procedures, the Centers for Disease Control and Prevention (CDC), in collaboration with the National Highway Traffic Safety Administration and the American College of Surgeons-Committee on Trauma, convened the National Expert Panel on Field Triage to update the Field Triage Decision Scheme: The National Trauma Triage Protocol (Decision Scheme). In support of the Decision Scheme, CDC developed educational resources for emergency medical service (EMS) professionals, one of CDC's first efforts to develop and broadly disseminate educational information for the EMS community. CDC wanted to systematically collect information from the EMS community on what worked and what did not with respect to these educational materials and which materials were of most use. An evaluation was conducted to obtain feedback from EMS professionals about the Decision Scheme and use of Decision Scheme educational materials. The evaluation included a survey and a series of focus groups. Findings indicate that a segment of the Decision Scheme's intended audience is using the materials and learning from them, and they have had a positive influence on their triage practices. However, many of the individuals who participated in this research are not using the Decision Scheme and indicated that the materials have not affected their triage practices. Findings presented in this article can be used to inform development and distribution of additional Decision Scheme educational resources to ensure they reach a greater proportion of EMS professionals and to inform other education and dissemination efforts with the EMS community. PMID- 22773615 TI - Process evaluation of a lifestyle intervention to prevent diabetes and cardiovascular diseases in primary care. AB - Effective, cost-effective, safe, and feasible interventions to improve lifestyle behavior in at-risk populations are needed in primary care. In the Hoorn Prevention Study, the authors implemented a theory-based lifestyle intervention in which trained practice nurses used an innovative combination of motivational interviewing (MI) and problem-solving treatment (PST). This article presents the intervention's reach, effectiveness in terms of process outcomes, adoption, and implementation. Recruitment strategy and participant flow were documented accurately. The effectiveness in terms of determinants of behavioral change was measured using a validated questionnaire. Questionnaires were also used to assess participant satisfaction and compliance, as well as practice nurses' confidence in providing the intervention. Counseling sessions were tape recorded to assess MI, PST, and general counseling competence. The findings indicate that the recruitment strategy was adequate and resulted in a reasonably extensive reach of the target population. Practice nurses were competent and confident in their provision of MI and PST, and participant satisfaction was high. Nevertheless, the number of sessions attended was low, and almost no effects were seen on determinants of behavioral change. The authors conclude that implementing this type of intervention in primary care is feasible, but more is needed to effectively facilitate changes in determinants of lifestyle behavior in this population. PMID- 22773618 TI - "I'm ready to eat and grab whatever I can get": Determinants and patterns of African American men's eating practices. AB - This article examines determinants and patterns of African American men's dietary practices. Thematic content analysis was used to analyze data from nine exploratory focus groups conducted with 83 urban, middle-aged and older African American men from southeast Michigan. The men distinguished between healthy and unhealthy foods and "meals" versus other instances of eating. Eating patterns and content differed depending on the meal, work and family schedules, food availability, and whether it was a weekday or weekend. When eating alone or outside the home, men prioritized convenience and preferences for tasty, unhealthy foods. Men often reported skipping breakfast or lunch and grabbing snacks or fast food during the day. They emphasized sharing dinner with their spouses and families-usually a home-cooked, "healthy" meal. On weekends, spouses often cooked less and men snacked and dined out more frequently. Sunday dinners involving favorite, unhealthy comfort foods were the highlight of men's eating practices. African American men tended not to follow healthy eating recommendations because of their busy lives, reliance on spouses to prepare food, and preferences for unhealthy foods. These findings suggest that healthy eating interventions must consider how the contexts of African American men's lives shape their eating practices. PMID- 22773619 TI - A process evaluation of a social cognitive theory-based childhood obesity prevention intervention: the Comics for Health program. AB - Process evaluations are an often overlooked yet essential component of health promotion interventions. This study reports the results of a comprehensive process evaluation for the "Comics for Health" program, a childhood obesity prevention intervention implemented at 12 after-school programs. Qualitative and quantitative process data were collected using surveys, field notes, and open item questionnaires, which assessed program fidelity, dose delivered, dose received, reach, recruitment, and context. Triangulation of methods was also employed to better understand how the program was implemented and received by the facilitator, staff members, and children in the program. Results indicated that program implementation had an almost perfect rate of fidelity with most lessons recording 100% tasks completed. Lessons were implemented in their intended order and lasted approximately 30 minutes as planned. After-school staff members reported that the program was well received by children, and this program should be replicated in the future. Attendance records showed that a majority of the children attended each lesson on the initial day of delivery (70.4%) and informal make-up lessons were implemented to compensate for the other children. Finally, several known sources of contamination were found such as past and concurrent exposure to similar health promotion interventions, which could potentially influence study outcomes. These findings will be used to help explain the results of this intervention and make recommendations for future intervention efforts. PMID- 22773620 TI - Being part of something: transformative outcomes of a community-based participatory study. AB - OBJECTIVES: Calls for public health practices, including research, to better integrate social theories of power, agency, and social change suggest that increased reflexivity about both the process and outcomes of community engagement is warranted. Yet few community-based participatory research (CBPR) projects specifically report nonresearch outcomes of such projects. The authors analyzed "secondary outcomes" of Protecting the 'Hood Against Tobacco (PHAT), a CBPR project conducted in San Francisco, California. METHODS: Interpretive analysis of quasi-ethnographic project documentation, including meeting minutes, field notes, retrospective observations, and interviews. RESULTS: PHAT participation created "ripple effects," encouraging healthier behaviors and public health promotion among community research partners, prompting academics to confront power asymmetries and recognize community knowledge, and widening social networks. CONCLUSIONS: CBPR benefits both communities and researchers beyond the findings of the research itself. More systematically capturing these effects, perhaps through wider use of ethnographic approaches, could help enhance understanding of CBPR's true contributions. PMID- 22773621 TI - Readiness for smoke-free policy and overall strength of tobacco control in rural tobacco-growing communities. AB - Rural, tobacco-growing areas are disproportionately affected by tobacco use, secondhand smoke, and weak policies. The study determined whether overall strength of Resources, Capacity, and Efforts in tobacco control predicts readiness for smoke-free policy in rural communities, controlling for county population size and pounds of tobacco produced. This was a correlational, cross sectional analysis of data from key informants (n = 148) and elected officials (n = 83) from 30 rural counties who participated in telephone interviews examining smoke-free policy. Six dimensions of community readiness (knowledge, leadership, resources, community climate, existing smoke-free policies, and political climate) were identified and summed to assess overall readiness for smoke-free policy. General strength of overall Resources, Capacity and Efforts in tobacco control at the county level was measured. Readiness for smoke-free policy was lower in communities with higher smoking rates, higher tobacco production, and smaller population. Efforts related to general tobacco control (i.e., media advocacy, training, and technical assistance) predicted readiness for local smoke free policy development (standardized beta = .35, p = .05), controlling for county population size and pounds of tobacco produced. Given that small, rural tobacco-growing communities are least ready for smoke-free policy change, tailoring and testing culturally sensitive approaches that account for this tobacco-growing heritage are warranted. PMID- 22773622 TI - Preparing for bike-sharing: insight from focus groups and surveys, Chattanooga, Tennessee, 2010. AB - OBJECTIVES: To obtain in-depth community input using qualitative and quantitative methods to guide development and marketing of a bike-share program in Chattanooga, Tennessee. METHOD: Focus groups and surveys assessed bicycling attitudes, beliefs, barriers, and behaviors of residents, workers, and university students. The authors completed nine focus groups (N = 56): five sessions with downtown workers, three with downtown residents, and one with university students. RESULTS: Health, recreation and transportation benefits of bicycling were commonly identified. Concerns regarding bicycling in traffic are apparent because of lack of facilities and a need for public education on safe motorist and bicyclist behavior. Practical limitations can inhibit bicycling during the day, including shower access and personal hygiene concerns. CONCLUSIONS: Public desire for environmental, educational, and enforcement tactics to support safe bicycling was noted. Marketing tactics for bike-share usage should emphasize health, recreational, and transportation benefits. Worksites can reduce barriers related to bicycling and encourage bike-share use. Future studies should assess bike-share impact on perceptions and behavior, as well as the resulting policy and environmental changes. PMID- 22773623 TI - Advocacy evaluation: challenges and emerging trends. AB - Devising, promoting, and implementing changes in policies and regulations are important components of population-level health promotion. Whether advocating for changes in school meal nutrition standards or restrictions on secondhand smoke, policy change can create environments conducive to healthier choices. Such policy changes often result from complex advocacy efforts that do not lend themselves to traditional evaluation approaches. In a challenging fiscal environment, allocating scarce resources to policy advocacy may be particularly difficult. A well-designed evaluation that moves beyond inventorying advocacy activities can help make the case for funding advocacy and policy change efforts. Although it is one thing to catalog meetings held, position papers drafted, and pamphlets distributed, it is quite another to demonstrate that these outputs resulted in useful policy change outcomes. This is where the emerging field of advocacy evaluation fits in by assessing (among other things) strategic learning, capacity building, and community organizing. Based on recent developments, this article highlights several challenges advocacy evaluators are currently facing and provides new resources for addressing them. PMID- 22773624 TI - Genetic diversity among Bacillus anthracis soil isolates at fine geographic scales. AB - Environmental samples were collected from carcass sites during and after anthrax outbreaks in 2000 and 2001 in the bison (Bison bison) population within Wood Buffalo National Park and the Hook Lake Region north of Wood Buffalo National Park. Bacillus anthracis spores were isolated from these samples and confirmed using phenotypic characterization and real-time PCR. Confirmed B. anthracis isolates were typed using multiple-locus variable-number tandem repeat analysis (MLVA15) and single-nucleotide-repeat analysis (SNRA). B. anthracis isolates split into two clades based on MLVA15, while SNRA allowed some isolates between carcass sites to be distinguished from each other. SNRA polymorphisms were also present within a single carcass site. Some isolates from different carcass sites having the same SNRA type had divergent MLVA types; this finding leads to questions about hierarchical typing methods and the robustness of the fine-scale typing of Bacillus anthracis. PMID- 22773625 TI - Association of fecal indicator bacteria with human viruses and microbial source tracking markers at coastal beaches impacted by nonpoint source pollution. AB - Water quality was assessed at two marine beaches in California by measuring the concentrations of culturable fecal indicator bacteria (FIB) and by library independent microbial source tracking (MST) methods targeting markers of human associated microbes (human polyomavirus [HPyV] PCR and quantitative PCR, Methanobrevibacter smithii PCR, and Bacteroides sp. strain HF183 PCR) and a human pathogen (adenovirus by nested PCR). FIB levels periodically exceeded regulatory thresholds at Doheny and Avalon Beaches for enterococci (28.5% and 31.7% of samples, respectively) and fecal coliforms (20% and 5.8%, respectively). Adenoviruses were detected at four of five sites at Doheny Beach and were correlated with detection of HPyVs and human Bacteroides HF183; however, adenoviruses were not detected at Avalon Beach. The most frequently detected human source marker at both beaches was Bacteroides HF183, which was detected in 27% of samples. Correlations between FIBs and human markers were much more frequent at Doheny Beach than at Avalon Beach; e.g., adenovirus was correlated with HPyVs and HF183. Human sewage markers and adenoviruses were routinely detected in samples meeting FIB regulatory standards. The toolbox approach of FIB measurement coupled with analysis of several MST markers targeting human pathogens used here demonstrated that human sewage is at least partly responsible for the degradation of water quality, particularly at Doheny Beach, and resulted in a more definitive assessment of recreational water quality and human health risk than reliance on FIB concentrations alone could have provided. PMID- 22773626 TI - Weak transcription of the cry1Ac gene in nonsporulating Bacillus thuringiensis cells. AB - The cry1Ac gene of Bacillus thuringiensis subsp. kurstaki HD-73 (B. thuringiensis HD-73) is a typical example of a sporulation-dependent crystal gene and is controlled by sigma E and sigma K during sporulation. To monitor the production and accumulation of Cry1Ac at the cellular level, we developed a green fluorescent protein-based reporter system. The production of Cry1Ac was monitored in spo0A, sigE, and sigK mutants, and these mutants were able to express the Cry1Ac-green fluorescent protein fusion protein. In nonsporulating B. thuringiensis HD-73 cells, low-level expression of cry1Ac was also observed. Reverse transcription-PCR and Western blotting results confirmed that the cry1Ac promoter has low activity in nonsporulating B. thuringiensis cells. A beta galactosidase assay demonstrated that the transcription of the cry1Ac gene during exponential and transition phases is positively regulated by Spo0A. Additional bioassay results indicated that spo0A and sigE mutants containing the cry1Ac-gfp fusion exhibited insecticidal activity against Plutella xylostella larvae. PMID- 22773627 TI - Dynamic viral populations in hypersaline systems as revealed by metagenomic assembly. AB - Viruses of the Bacteria and Archaea play important roles in microbial evolution and ecology, and yet viral dynamics in natural systems remain poorly understood. Here, we created de novo assemblies from 6.4 Gbp of metagenomic sequence from eight community viral concentrate samples, collected from 12 h to 3 years apart from hypersaline Lake Tyrrell (LT), Victoria, Australia. Through extensive manual assembly curation, we reconstructed 7 complete and 28 partial novel genomes of viruses and virus-like entities (VLEs, which could be viruses or plasmids). We tracked these 35 populations across the eight samples and found that they are generally stable on the timescale of days and transient on the timescale of years, with some exceptions. Cross-detection of the 35 LT populations in three previously described haloviral metagenomes was limited to a few genes, and most previously sequenced haloviruses were not detected in our samples, though 3 were detected upon reducing our detection threshold from 90% to 75% nucleotide identity. Similar results were obtained when we applied our methods to haloviral metagenomic data previously reported from San Diego, CA: 10 contigs that we assembled from that system exhibited a variety of detection patterns on a timescale of weeks to 1 month but were generally not detected in LT. Our results suggest that most haloviral populations have a limited or, possibly, a temporally variable global distribution. This study provides high-resolution insight into viral biogeography and dynamics and it places "snapshot" viral metagenomes, collected at a single time and location, in context. PMID- 22773628 TI - Exploring the natural fungal biodiversity of tropical and temperate forests toward improvement of biomass conversion. AB - In this study, natural fungal diversity in wood-decaying species was explored for biomass deconstruction. In 2007 and 2008, fungal isolates were collected in temperate forests mainly from metropolitan France and in tropical forests mainly from French Guiana. We recovered and identified 74 monomorph cultures using morphological and molecular identification tools. Following production of fungal secretomes under inductive conditions, we evaluated the capacity of these fungal strains to potentiate a commercial Trichoderma reesei cellulase cocktail for the release of soluble sugars from biomass. The secretome of 19 isolates led to an improvement in biomass conversion of at least 23%. Of the isolates, the Trametes gibbosa BRFM 952 (Banque de Ressources Fongiques de Marseille) secretome performed best, with 60% improved conversion, a feature that was not universal to the Trametes and related genera. Enzymatic characterization of the T. gibbosa BRFM 952 secretome revealed an unexpected high activity on crystalline cellulose, higher than that of the T. reesei cellulase cocktail. This report highlights the interest in a systematic high-throughput assessment of collected fungal biodiversity to improve the enzymatic conversion of lignocellulosic biomass. It enabled the unbiased identification of new fungal strains issued from biodiversity with high biotechnological potential. PMID- 22773629 TI - Phosphate starvation promotes swarming motility and cytotoxicity of Pseudomonas aeruginosa. AB - We investigated the transcriptional responses of Pseudomonas aeruginosa under phosphate-deficient (0.2 mM) conditions compared to phosphate sufficiency (1 mM). This elicited enormous transcriptional changes in genes related to phosphate acquisition, quorum sensing, chemotaxis, toxin secretion, and regulation. This dysregulation also led to increased virulence-associated phenotypes, including swarming motility and cytotoxicity. PMID- 22773630 TI - Substrate and inhibitor spectra of ethylbenzene dehydrogenase: perspectives on application potential and catalytic mechanism. AB - Ethylbenzene dehydrogenase (EbDH) catalyzes the initial step in anaerobic degradation of ethylbenzene in denitrifying bacteria, namely, the oxygen independent hydroxylation of ethylbenzene to (S)-1-phenylethanol. In our study we investigate the kinetic properties of 46 substrate analogs acting as substrates or inhibitors of the enzyme. The apparent kinetic parameters of these compounds give important insights into the function of the enzyme and are consistent with the predicted catalytic mechanism based on a quantum chemical calculation model. In particular, the existence of the proposed substrate-derived radical and carbocation intermediates is substantiated by the formation of alternative dehydrogenated and hydroxylated products from some substrates, which can be regarded as mechanistic models. In addition, these results also show the surprisingly high diversity of EbDH in hydroxylating different kinds of alkylaromatic and heterocyclic compounds to the respective alcohols. This may lead to attractive industrial applications of ethylbenzene dehydrogenase for a new process of producing alcohols via hydroxylation of the corresponding aromatic hydrocarbons rather than the customary procedure of reducing the corresponding ketones. PMID- 22773631 TI - The bacterium Pantoea stewartii uses two different type III secretion systems to colonize its plant host and insect vector. AB - Plant- and animal-pathogenic bacteria utilize phylogenetically distinct type III secretion systems (T3SS) that produce needle-like injectisomes or pili for the delivery of effector proteins into host cells. Pantoea stewartii subsp. stewartii (herein referred to as P. stewartii), the causative agent of Stewart's bacterial wilt and leaf blight of maize, carries phylogenetically distinct T3SSs. In addition to an Hrc-Hrp T3SS, known to be essential for maize pathogenesis, P. stewartii has a second T3SS (Pantoea secretion island 2 [PSI-2]) that is required for persistence in its flea beetle vector, Chaetocnema pulicaria (Melsh). PSI-2 belongs to the Inv-Mxi-Spa T3SS family, typically found in animal pathogens. Mutagenesis of the PSI-2 psaN gene, which encodes an ATPase essential for secretion of T3SS effectors by the injectisome, greatly reduces both the persistence of P. stewartii in flea beetle guts and the beetle's ability to transmit P. stewartii to maize. Ectopic expression of the psaN gene complements these phenotypes. In addition, the PSI-2 psaN gene is not required for P. stewartii pathogenesis of maize and is transcriptionally upregulated in insects compared to maize tissues. Thus, the Hrp and PSI-2 T3SSs play different roles in the life cycle of P. stewartii as it alternates between its insect vector and plant host. PMID- 22773632 TI - Fast and sensitive detection of Bacillus anthracis spores by immunoassay. AB - Bacillus anthracis is one of the most dangerous potential biological weapons, and it is essential to develop a rapid and simple method to detect B. anthracis spores in environmental samples. The immunoassay is a rapid and easy-to-use method for the detection of B. anthracis by means of antibodies directed against surface spore antigens. With this objective in view, we have produced a panel of monoclonal antibodies against B. anthracis and developed colorimetric and electrochemiluminescence (ECL) immunoassays. Using Meso Scale Discovery ECL technology, which is based on electrochemiluminescence (ECL) detection utilizing a sulfo-Tag label that emits light upon electrochemical stimulation (using a dedicated ECL plate reader, an electrical current is placed across the microplate with electrodes integrated into the bottom of the plate, resulting in a series of electrically induced reactions leading to a luminescent signal), a detection limit ranging between 0.3 * 10(3) and 10(3) CFU/ml (i.e., 30 to 100 spores per test), depending on the B. anthracis strain assayed, was achieved. In complex matrices (5 mg/ml of soil or simulated powder), the detection level (without any sample purification or concentration) was never altered more than 3-fold compared with the results obtained in phosphate-buffered saline. PMID- 22773633 TI - Novel mutations associated with resistance to Bacillus sphaericus in a polymorphic region of the Culex quinquefasciatus cqm1 gene. AB - Bin toxin from Bacillus sphaericus acts on Culex quinquefasciatus larvae by binding to Cqm1 midgut-bound receptors, and disruption of the cqm1 gene is the major cause of resistance. The goal of this work was to screen for a laboratory selected resistance cqm1(REC) allele in field populations in the city of Recife, Brazil, and to describe other resistance-associated polymorphisms in the cqm1 gene. The cqm1(REC) allele was detected in the four nontreated populations surveyed at frequencies from 0.001 to 0.017, and sequence analysis from these samples revealed a novel resistant allele (cqm1(REC-D16)) displaying a 16 nucletotide (nt) deletion which is distinct from the 19-nt deletion associated with cqm1(REC). Yet a third resistant allele (cqm1(REC-D25)), displaying a 25-nt deletion, was identified in samples from a treated area exposed to B. sphaericus. A comparison of the three deletion events revealed that all are located within the same 208-nt region amplified during the screening procedure. They also introduce equivalent frameshifts in the sequence and generate the same premature stop codon, leading to putative transcripts encoding truncated proteins which are unable to locate to the midgut epithelium. The populations analyzed in this study contained a variety of alleles with mutations disrupting the function of the corresponding Bin toxin receptor. Their locations reveal a hot spot that can be exploited to assess the resistance risk through DNA screening. PMID- 22773634 TI - Lack of Cry1Fa binding to the midgut brush border membrane in a resistant colony of Plutella xylostella moths with a mutation in the ABCC2 locus. AB - Previous studies reported "mode 1" Bacillus thuringiensis resistance in a colony of diamondback moths (NO-QA), and recently, this resistance has been mapped to an ABC transporter (ABCC2) locus. We report the lack of binding of Cry1Fa to insects derived from this colony and compare our data with those from other insects with ABCC2-associated resistance. PMID- 22773635 TI - Evaluation of near-infrared pasteurization in controlling Escherichia coli O157:H7, Salmonella enterica serovar typhimurium, and Listeria monocytogenes in ready-to-eat sliced ham. AB - This study was conducted to investigate the efficacy of near-infrared (NIR) heating to reduce Salmonella enterica serovar Typhimurium, Escherichia coli O157:H7, and Listeria monocytogenes in ready-to-eat (RTE) sliced ham compared to conventional convective heating, and the effect of NIR heating on quality was determined by measuring the color and texture change. A cocktail of three pathogens was inoculated on the exposed or protected surfaces of ham slices, followed by NIR or conventional heating at 1.8 kW. NIR heating for 50 s achieved 4.1-, 4.19-, and 3.38-log reductions in surface-inoculated S. Typhimurium, E. coli O157:H7, and L. monocytogenes, respectively, whereas convective heating needed 180 s to attain comparable reductions for each pathogen. There were no statistically significant (P > 0.05) differences in reduction between surface- and internally inoculated pathogens at the end of NIR treatment (50 s). However, when treated with conventional convective heating, significant (P < 0.05) differences were observed at the final stages of the treatment (150 and 180 s). Color values and texture parameters of NIR-treated (50-s treatment) ham slices were not significantly (P > 0.05) different from those of nontreated samples. These results suggest that NIR heating can be applied to control internalized pathogens as well as surface-adhering pathogens in RTE sliced meats without affecting product quality. PMID- 22773636 TI - Bacterial associates of two Caribbean coral species reveal species-specific distribution and geographic variability. AB - Scleractinian corals harbor microorganisms that form dynamic associations with the coral host and exhibit substantial genetic and ecological diversity. Microbial associates may provide defense against pathogens and serve as bioindicators of changing environmental conditions. Here we describe the bacterial assemblages associated with two of the most common and phylogenetically divergent reef-building corals in the Caribbean, Montastraea faveolata and Porites astreoides. Contrasting life history strategies and disease susceptibilities indicate potential differences in their microbiota and immune function that may in part drive changes in the composition of coral reef communities. The ribotype structure and diversity of coral-associated bacteria within the surface mucosal layer (SML) of healthy corals were assessed using denaturing gradient gel electrophoresis (DGGE) fingerprinting and 454 bar-coded pyrosequencing. Corals were sampled at disparate Caribbean locations representing various levels of anthropogenic impact. We demonstrate here that M. faveolata and P. astreoides harbor distinct, host-specific bacteria but that specificity varies by species and site. P. astreoides generally hosts a bacterial assemblage of low diversity that is largely dominated by one bacterial genus, Endozoicomonas, within the order Oceanospirillales. The bacterial assemblages associated with M. faveolata are significantly more diverse and exhibit higher specificity at the family level than P. astreoides assemblages. Both corals have more bacterial diversity and higher abundances of disease-related bacteria at sites closer to the mainland than at those furthest away. The most diverse bacterial taxa and highest relative abundance of disease-associated bacteria were seen for corals near St. Thomas, U.S. Virgin Islands (USVI) (2.5 km from shore), and the least diverse taxa and lowest relative abundance were seen for corals near our most pristine site in Belize (20 km from shore). We conclude that the two coral species studied harbor distinct bacterial assemblages within the SML, but the degree to which each species maintains specific microbial associations varies both within each site and across large spatial scales. The taxonomic scale (i.e., phylum versus genus) at which scientists examine coral-microbe associations, in addition to host-elicited factors and environmental fluctuations, must be considered carefully in future studies of the coral holobiont. PMID- 22773637 TI - Comparative inactivation of murine norovirus, human adenovirus, and human JC polyomavirus by chlorine in seawater. AB - Viruses excreted by humans affect the commercial and recreational use of coastal water. Shellfish produced in contaminated waters have been linked to many episodes and outbreaks of viral gastroenteritis, as well as other food-borne diseases worldwide. The risk can be reduced by appropriate treatment following harvesting and by depuration. The kinetics of inactivation of murine norovirus 1 and human adenovirus 2 in natural and artificial seawater by free available chlorine was studied by quantifying genomic copies (GC) using quantitative PCR and infectious viral particles (PFU). Human JC polyomavirus Mad4 kinetics were evaluated by quantitative PCR. DNase or RNase were used to eliminate free genomes and assess potential viral infectivity when molecular detection was performed. At 30 min of assay, human adenovirus 2 showed 2.6- and 2.7-log(10) GC reductions and a 2.3- and 2.4-log(10) PFU reductions in natural and artificial seawater, respectively, and infectious viral particles were still observed at the end of the assay. When DNase was used prior to the nucleic acid extraction the kinetic of inactivation obtained by quantitative PCR was statistically equivalent to the one observed by infectivity assays. For murine norovirus 1, 2.5, and 3.5-log(10) GC reductions were observed in natural and artificial seawater, respectively, while no viruses remained infectious after 30 min of contact with chlorine. Regarding JC polyomavirus Mad4, 1.5- and 1.1-log(10) GC reductions were observed after 30 min of contact time. No infectivity assays were conducted for this virus. The results obtained provide data that might be applicable to seawater used in shellfish depuration. PMID- 22773638 TI - Comparative assessment of nitrogen fixation methodologies, conducted in the oligotrophic North Pacific Ocean. AB - Resolution of the nitrogen (N) cycle in the marine environment requires an accurate assessment of dinitrogen (N(2)) fixation. We present here an update on progress in conducting field measurements of acetylene reduction (AR) and (15)N(2) tracer assimilation in the oligotrophic North Pacific Subtropical Gyre (NPSG). The AR assay was conducted on discrete seawater samples using a headspace analysis system, followed by quantification of ethylene (C(2)H(4)) with a reducing compound photodetector. The rates of C(2)H(4) production were measurable for nonconcentrated seawater samples after an incubation period of 3 to 4 h. The (15)N(2) tracer measurements compared the addition of (15)N(2) as a gas bubble and dissolved as (15)N(2) enriched seawater. On all sampling occasions and at all depths, a 2- to 6-fold increase in the rate of (15)N(2) assimilation was measured when (15)N(2)-enriched seawater was added to the seawater sample compared to the addition of (15)N(2) as a gas bubble. In addition, we show that the (15)N(2) enriched seawater can be prepared prior to its use with no detectable loss (<1.7%) of dissolved (15)N(2) during 4 weeks of storage, facilitating its use in the field. The ratio of C(2)H(4) production to (15)N(2) assimilation varied from 7 to 27 when measured simultaneously in surface seawater samples. Collectively, the modifications to the AR assay and the (15)N(2) assimilation technique present opportunities for more accurate and high frequency measurements (e.g., diel scale) of N(2) fixation, providing further insight into the contribution of different groups of diazotrophs to the input of N in the global oceans. PMID- 22773639 TI - Discerning the role of Bacteroides fragilis in celiac disease pathogenesis. AB - Celiac disease (CD) is associated with intestinal dysbiosis, which can theoretically lead to dysfunctions in host-microbe interactions and contribute to the disease. In the present study, possible differences in Bacteroides spp. and their pathogenic features between CD patients and controls were investigated. Bacteroides clones (n = 274) were isolated, identified, and screened for the presence of the virulence genes (bft and mpII) coding for metalloproteases. The proteolytic activity of selected Bacteroides fragilis strains was evaluated by zymography and, after gastrointestinal digestion of gliadin, by high-pressure liquid chromatography/electrospray ionization/tandem mass spectrometry. The effects of B. fragilis strains on Caco-2 cell culture permeability and inflammatory response to digested gliadin were determined. B. fragilis was more frequently identified in CD patients than in healthy controls, in contrast to Bacteroides ovatus. B. fragilis clones carrying virulence genes coding for metalloproteases were more abundant in CD patients than in controls. B. fragilis strains, representing the isolated clones and carrying metalloprotease genes, showed gelatinase activity and exerted the strongest adverse effects on the integrity of the Caco-2 cell monolayer. All B. fragilis strains also showed gliadin-hydrolyzing activity, and some of them generated immunogenic peptides that preserved or increased inflammatory cytokine production (tumor necrosis factor alpha) and showed increased ability to permeate through Caco-2 cell cultures. These findings suggest that increased abundance of B. fragilis strains with metalloprotease activities could play a role in CD pathogenesis, although further in vivo studies are required to support this hypothesis. PMID- 22773640 TI - A convenient and robust in vivo reporter system to monitor gene expression in the human pathogen Helicobacter pylori. AB - Thirty years of intensive research have significantly contributed to our understanding of Helicobacter pylori biology and pathogenesis. However, the lack of convenient genetic tools, in particular the limited effectiveness of available reporter systems, has notably limited the toolbox for fundamental and applied studies. Here, we report the construction of a bioluminescent H. pylori reporter system based on the Photorhabdus luminescens luxCDABE cassette. The system is constituted of a promoterless lux acceptor strain in which promoters and sequences of interest can be conveniently introduced by double homologous recombination of a suicide transformation vector. We validate the robustness of this new lux reporter system in noninvasive in vivo monitoring of dynamic transcriptional responses of inducible as well as repressible promoters and demonstrate its suitability for the implementation of genetic screens in H. pylori. PMID- 22773641 TI - Comparative analysis of mycobacterial truncated hemoglobin promoters and the groEL2 promoter in free-living and intracellular mycobacteria. AB - The success of Mycobacterium tuberculosis depends on its ability to withstand and survive the hazardous environment inside the macrophages that are created by reactive oxygen intermediates, reactive nitrogen intermediates, severe hypoxia, low pH, and high CO(2) levels. Therefore, an effective detoxification system is required for the pathogen to persist in vivo. The genome of M. tuberculosis contains a new family of hemoproteins named truncated hemoglobin O (trHbO) and truncated hemoglobin N (trHbN), encoded by the glbO and glbN genes, respectively, important in the survival of M. tuberculosis in macrophages. Mycobacterial heat shock proteins are known to undergo rapid upregulation under stress conditions. The expression profiles of the promoters of these genes were studied by constructing transcriptional fusions with green fluorescent protein and monitoring the promoter activity in both free-living and intracellular milieus at different time points. Whereas glbN showed an early response to the oxidative and nitrosative stresses tested, glbO gave a lasting response to lower concentrations of both stresses. At all time points and under all stress conditions tested, groEL2 showed higher expression than both trHb promoters and expression of both promoters showed an increase while inside the macrophages. Real-time PCR analysis of trHb and groEL2 mRNAs showed an initial upregulation at 24 h postinfection. The presence of the glbO protein imparted an increased survival to M. smegmatis in THP-1 differentiated macrophages compared to that imparted by the glbN and hsp65 proteins. The comparative upregulation shown by both trHb promoters while grown inside macrophages indicates the importance of these promoters for the survival of M. tuberculosis in the hostile environment of the host. PMID- 22773642 TI - Culture- and quantitative IS900 real-time PCR-based analysis of the persistence of Mycobacterium avium subsp. paratuberculosis in a controlled dairy cow farm environment. AB - The aim of this study was to monitor the persistence of Mycobacterium avium subsp. paratuberculosis in environmental samples taken from a Holstein farm with a long history of clinical paratuberculosis. A herd of 606 head was eradicated, and mechanical cleaning and disinfection with chloramine B with ammonium (4%) was carried out on the farm; in the surrounding areas (on the field and field midden) lime was applied. Environmental samples were collected before and over a period of 24 months after destocking. Only one sample out of 48 (2%) examined on the farm (originating from a waste pit and collected before destocking) was positive for M. avium subsp. paratuberculosis by cultivation on solid medium (Herrold's egg yolk medium). The results using real-time quantitative PCR (qPCR) showed that a total of 81% of environmental samples with an average mean M. avium subsp. paratuberculosis cell number of 3.09 * 10(3) were positive for M. avium subsp. paratuberculosis before destocking compared to 43% with an average mean M. avium subsp. paratuberculosis cell number of 5.86 * 10(2) after 24 months. M. avium subsp. paratuberculosis-positive samples were detected in the cattle barn as well as in the calf barn and surrounding areas. M. avium subsp. paratuberculosis was detected from different matrices: floor and instrument scrapings, sediment, or scraping from watering troughs, waste pits, and cobwebs. M. avium subsp. paratuberculosis DNA was also detected in soil and plants collected on the field midden and the field 24 months after destocking. Although the proportion of positive samples decreased from 64% to 23% over time, the numbers of M. avium subsp. paratuberculosis cells were comparable. PMID- 22773643 TI - Impact of short-term acidification on nitrification and nitrifying bacterial community dynamics in soilless cultivation media. AB - Soilless medium-based horticulture systems are highly prevalent due to their capacity to optimize growth of high-cash crops. However, these systems are highly dynamic and more sensitive to physiochemical and pH perturbations than traditional soil-based systems, especially during nitrification associated with ammonia-based fertilization. The objective of this study was to assess the impact of nitrification-generated acidification on ammonia oxidation rates and nitrifying bacterial community dynamics in soilless growth media. To achieve this goal, perlite soilless growth medium from a commercial bell pepper greenhouse was incubated with ammonium in bench-scale microcosm experiments. Initial quantitative real-time PCR analysis indicated that betaproteobacterial ammonia oxidizers were significantly more abundant than ammonia-oxidizing archaea, and therefore, research focused on this group. Ammonia oxidation rates were highest between 0 and 9 days, when pH values dropped from 7.4 to 4.9. Pyrosequencing of betaproteobacterial ammonia-oxidizing amoA gene fragments indicated that r strategist-like Nitrosomonas was the dominant ammonia-oxidizing bacterial genus during this period, seemingly due to the high ammonium concentration and optimal growth conditions in the soilless media. Reduction of pH to levels below 4.8 resulted in a significant decrease in both ammonia oxidation rates and the diversity of ammonia-oxidizing bacteria, with increased relative abundance of the r-strategist-like Nitrosospira. Nitrite oxidizers (Nitrospira and Nitrobacter) were on the whole more abundant and less sensitive to acidification than ammonia oxidizers. This study demonstrates that nitrification and nitrifying bacterial community dynamics in high-N-load intensive soilless growth media may be significantly different from those in in-terra agricultural systems. PMID- 22773644 TI - Draft genome sequence of a psychrotolerant sulfur-oxidizing bacterium, Sulfuricella denitrificans skB26, and proteomic insights into cold adaptation. AB - Except for several conspicuous cases, very little is known about sulfur oxidizers living in natural freshwater environments. Sulfuricella denitrificans skB26 is a psychrotolerant sulfur oxidizer recently isolated from a freshwater lake as a representative of a new genus in the class Betaproteobacteria. In this study, an approximately 3.2-Mb draft genome sequence of strain skB26 was obtained. In the draft genome, consisting of 23 contigs, a single rRNA operon, 43 tRNA genes, and 3,133 coding sequences were identified. The identified genes include those required for sulfur oxidation, denitrification, and carbon fixation. Comparative proteomic analysis was conducted to assess cold adaptation mechanisms of this organism. From cells grown at 22 degrees C and 5 degrees C, proteins were extracted for analysis by nano-liquid chromatography-electrospray ionization tandem mass spectrometry. In the cells cultured at 5 degrees C, relative abundances of ribosomal proteins, cold shock proteins, and DEAD/DEAH box RNA helicases were increased in comparison to those at 22 degrees C. These results suggest that maintenance of proper translation is critical for growth under low temperature conditions, similar to the case for other cold-adapted prokaryotes. PMID- 22773645 TI - Unexpected specificity of interspecies cobamide transfer from Geobacter spp. to organohalide-respiring Dehalococcoides mccartyi strains. AB - Dehalococcoides mccartyi strains conserve energy from reductive dechlorination reactions catalyzed by corrinoid-dependent reductive dehalogenase enzyme systems. Dehalococcoides lacks the ability for de novo corrinoid synthesis, and pure cultures require the addition of cyanocobalamin (vitamin B(12)) for growth. In contrast, Geobacter lovleyi, which dechlorinates tetrachloroethene to cis-1,2 dichloroethene (cis-DCE), and the nondechlorinating species Geobacter sulfurreducens have complete sets of cobamide biosynthesis genes and produced 12.9 +/- 2.4 and 24.2 +/- 5.8 ng of extracellular cobamide per liter of culture suspension, respectively, during growth with acetate and fumarate in a completely synthetic medium. G. lovleyi-D. mccartyi strain BAV1 or strain FL2 cocultures provided evidence for interspecies corrinoid transfer, and cis-DCE was dechlorinated to vinyl chloride and ethene concomitant with Dehalococcoides growth. In contrast, negligible increase in Dehalococcoides 16S rRNA gene copies and insignificant dechlorination occurred in G. sulfurreducens-D. mccartyi strain BAV1 or strain FL2 cocultures. Apparently, G. lovleyi produces a cobamide that complements Dehalococcoides' nutritional requirements, whereas G. sulfurreducens does not. Interestingly, Dehalococcoides dechlorination activity and growth could be restored in G. sulfurreducens-Dehalococcoides cocultures by adding 10 MUM 5',6'-dimethylbenzimidazole. Observations made with the G. sulfurreducens Dehalococcoides cocultures suggest that the exchange of the lower ligand generated a cobalamin, which supported Dehalococcoides activity. These findings have implications for in situ bioremediation and suggest that the corrinoid metabolism of Dehalococcoides must be understood to faithfully predict, and possibly enhance, reductive dechlorination activities. PMID- 22773646 TI - Temporal dynamics and decay of putatively allochthonous and autochthonous viral genotypes in contrasting freshwater lakes. AB - Aquatic viruses play important roles in the biogeochemistry and ecology of lacustrine ecosystems; however, their composition, dynamics, and interactions with viruses of terrestrial origin are less extensively studied. We used a viral shotgun metagenomic approach to elucidate candidate autochthonous (i.e., produced within the lake) and allochthonous (i.e., washed in from other habitats) viral genotypes for a comparative study of their dynamics in lake waters. Based on shotgun metagenomes prepared from catchment soil and freshwater samples from two contrasting lakes (Cayuga Lake and Fayetteville Green Lake), we selected two putatively autochthonous viral genotypes (phycodnaviruses likely infecting algae and cyanomyoviruses likely infecting picocyanobacteria) and two putatively allochthonous viral genotypes (geminiviruses likely infecting terrestrial plants and circoviruses infecting unknown hosts but common in soil libraries) for analysis by genotype-specific quantitative PCR (TaqMan) applied to DNAs from viruses in the viral size fraction of lake plankton, i.e., 0.2 MUm > virus > 0.02 MUm. The abundance of autochthonous genotypes largely reflected expected host abundance, while the abundance of allochthonous genotypes corresponded with rainfall and storm events in the respective catchments, suggesting that viruses with these genotypes may have been transported to the lake in runoff. The decay rates of allochthonous and autochthonous genotypes, assessed in incubations where all potential hosts were killed, were generally lower (0.13 to 1.50% h(-1)) than those reported for marine virioplankton but similar to those for freshwater virioplankton. Both allochthonous and autochthonous viral genotypes were detected at higher concentrations in subsurface sediments than at the water-sediment interface. Our data indicate that putatively allochthonous viruses are present in lake plankton and sediments, where their temporal dynamics reflect active transport to the lake during hydrological events and then decay once there. PMID- 22773647 TI - Enumerating viruses by using fluorescence and the nature of the nonviral background fraction. AB - Bulk fluorescence measurements could be a faster and cheaper way of enumerating viruses than epifluorescence microscopy, flow cytometry, or transmission electron microscopy (TEM). However, since viruses are not imaged, the background fluorescence compromises the signal, and we know little about its nature. In this paper the size ranges of nucleotides that fluoresce in the presence of SYBR gold were determined for wastewater and a range of freshwater samples using a differential filtration method. Fluorescence excitation-emission matrices (FEEMs) showed that >70% of the SYBR fluorescence was in the <10-nm size fraction (background) and was not associated with intact viruses. This was confirmed using TEM. The use of FEEMs to develop a fluorescence-based method for counting viruses is an approach that is fundamentally different from the epifluorescence microscopy technique used for enumerating viruses. This high fluorescence background is currently overlooked, yet it has had a most pervasive influence on the development of a simple fluorescence-based method for quantifying viral abundance in water. PMID- 22773648 TI - Predicted protein subcellular localization in dominant surface ocean bacterioplankton. AB - Bacteria consume dissolved organic matter (DOM) through hydrolysis, transport and intracellular metabolism, and these activities occur in distinct subcellular localizations. Bacterial protein subcellular localizations for several major marine bacterial groups were predicted using genomic, metagenomic and metatranscriptomic data sets following modification of MetaP software for use with partial gene sequences. The most distinct pattern of subcellular localization was found for Bacteroidetes, whose genomes were substantially enriched with outer membrane and extracellular proteins but depleted of inner membrane proteins compared with five other taxa (SAR11, Roseobacter, Synechococcus, Prochlorococcus, oligotrophic marine Gammaproteobacteria). When subcellular localization patterns were compared between genes and transcripts, three taxa had expression biased toward proteins localized to cell locations outside of the cytosol (SAR11, Roseobacter, and Synechococcus), as expected based on the importance of carbon and nutrient acquisition in an oligotrophic ocean, but two taxa did not (oligotrophic marine Gammaproteobacteria and Bacteroidetes). Diel variations in the fraction and putative gene functions of transcripts encoding inner membrane and periplasmic proteins compared to cytoplasmic proteins suggest a close coupling of photosynthetic extracellular release and bacterial consumption, providing insights into interactions between phytoplankton, bacteria, and DOM. PMID- 22773649 TI - Structure-guided expansion of the substrate range of methylmalonyl coenzyme A synthetase (MatB) of Rhodopseudomonas palustris. AB - Malonyl coenzyme A (malonyl-CoA) and methylmalonyl-CoA are two of the most commonly used extender units for polyketide biosynthesis and are utilized to synthesize a vast array of pharmaceutically relevant products with antibacterial, antiparasitic, anticholesterol, anticancer, antifungal, and immunosuppressive properties. Heterologous hosts used for polyketide production such as Escherichia coli often do not produce significant amounts of methylmalonyl-CoA, however, requiring the introduction of other pathways for the generation of this important building block. Recently, the bacterial malonyl-CoA synthetase class of enzymes has been utilized to generate malonyl-CoA and methylmalonyl-CoA directly from malonate and methylmalonate. We demonstrate that in the purple photosynthetic bacterium Rhodopseudomonas palustris, MatB (RpMatB) acts as a methylmalonyl-CoA synthetase and is required for growth on methylmalonate. We report the apo (1.7-A resolution) and ATP-bound (2.0-A resolution) structure and kinetic analysis of RpMatB, which shows similar activities for both malonate and methylmalonate, making it an ideal enzyme for heterologous polyketide biosynthesis. Additionally, rational, structure-based mutagenesis of the active site of RpMatB led to substantially higher activity with ethylmalonate and butylmalonate, demonstrating that this enzyme is a prime target for expanded substrate specificity. PMID- 22773650 TI - Contribution of surfactin and SwrA to flagellin expression, swimming, and surface motility in Bacillus subtilis. AB - Multicellular communities produced by Bacillus subtilis can adopt sliding or swarming to translocate over surfaces. While sliding is a flagellum-independent motility produced by the expansive forces in a growing colony, swarming requires flagellar functionality and is characterized by the appearance of hyperflagellated swarm cells that associate in bundles or rafts during movement. Previous work has shown that swarming by undomesticated B. subtilis strains requires swrA, a gene that upregulates the expression of flagellar genes and increases swimming motility, and surfactin, a lipopeptide biosurfactant that also facilitates sliding. Through an analysis of swrA(+) and swrA mutant laboratory strains with or without a mutation in sfp (a gene involved in surfactin production), we show that both swrA and surfactin upregulate the transcription of the flagellin gene and increase bacterial swimming. Surfactin also allows the nonswarming swrA mutant strain to efficiently colonize moist surfaces by sliding. Finally, we reconfirm the essential role of swrA in swarming and show that surfactin, which increases surface wettability, allows swrA(+) strains to produce swarm cells on media at low humidity. PMID- 22773651 TI - NasT-mediated antitermination plays an essential role in the regulation of the assimilatory nitrate reductase operon in Azotobacter vinelandii. AB - Azotobacter vinelandii is a well-studied model system for nitrogen fixation in bacteria. Regulation of nitrogen fixation in A. vinelandii is independent of NtrB/NtrC, a conserved nitrogen regulatory system in proteobacteria. Previous work showed that an ntrC mutation in A. vinelandii resulted in a loss of induction of assimilatory nitrate and nitrite reductases encoded by the nasAB operon. In addition to NtrC, several other proteins, including NasT, a protein containing a potential RNA-binding domain ANTAR (AmiR and NasR transcription antitermination regulators), have been implicated in nasAB regulation. In this work, we characterize the sequence upstream of nasA and identify several DNA sequence elements, including two potential NtrC binding sites and a putative intrinsic transcriptional terminator upstream of nasA that are potentially involved in nasAB regulation. Our analyses confirm that the nasAB promoter, P(nasA), is under NtrC control. However, unlike NtrC-regulated promoters in enteric bacteria, P(nasA) shows high activity in the presence of ammonium; in addition, the P(nasA) activity is altered in the nifA gene mutation background. We discuss the implication of these results on NtrC-mediated regulation in A. vinelandii. Our study provides direct evidence that induction of nasAB is regulated by NasT-mediated antitermination, which occurs within the leader region of the operon. The results also support the hypothesis that NasT binds the promoter proximal hairpin of nasAB for its regulatory function, which contributes to the understanding of the regulatory mechanism of ANTAR-containing antiterminators. PMID- 22773652 TI - Genetic diversity and mating type distribution of Tuber melanosporum and their significance to truffle cultivation in artificially planted truffieres in Australia. AB - Tuber melanosporum is a truffle native to Europe and is cultivated in countries such as Australia for the gastronomic market, where production yields are often lower than expected. We assessed the genetic diversity of T. melanosporum with six microsatellite loci to assess the effect of genetic drift on truffle yield in Australia. Genetic diversity as assessed on 210 ascocarps revealed a higher allelic diversity compared to previous studies from Europe, suggesting a possible genetic expansion and/or multiple and diverse source populations for inoculum. The results also suggest that the single sequence repeat diversity of locus ME2 is adaptive and that, for example, the probability of replication errors is increased for this locus. Loss of genetic diversity in Australian populations is therefore not a likely factor in limiting ascocarp production. A survey of nursery seedlings and trees inoculated with T. melanosporum revealed that <70% of seedlings and host trees were colonized with T. melanosporum and that some trees had been contaminated by Tuber brumale, presumably during the inoculation process. Mating type (MAT1-1-1 and MAT1-2-1) analyses on seedling and four- to ten-year-old host trees found that 100% of seedlings but only approximately half of host trees had both mating types present. Furthermore, MAT1-1-1 was detected significantly more commonly than MAT1-2-1 in established trees, suggesting a competitive advantage for MAT1-1-1 strains. This study clearly shows that there are more factors involved in ascocarp production than just the presence of both mating types on host trees. PMID- 22773653 TI - Characterization of a novel microcin that kills enterohemorrhagic Escherichia coli O157:H7 and O26. AB - A novel phenotype was recently identified in which specific strains of Escherichia coli inhibit competing E. coli strains via a mechanism that was designated "proximity-dependent inhibition" (PDI). PDI-expressing (PDI(+)) E. coli is known to inhibit susceptible (PDI(-)) E. coli strains, including several enterohemorrhagic (EHEC) and enterotoxigenic (ETEC) E. coli strains. In this study, every strain from a genetically diverse panel of E. coli O157:H7 (n = 25) and additional strains of E. coli serovar O26 were susceptible to the PDI phenotype. LIVE/DEAD staining was consistent with inhibition by killing of susceptible cells. Comparative genome analysis identified the genetic component of PDI, which is composed of a plasmid-borne (Incl1) operon encoding a putative microcin and associated genes for transport, immunity, and microcin activation. Transfer of the plasmid to a PDI(-) strain resulted in transfer of the phenotype, and deletion of the genes within the operon resulted in loss of the inhibition phenotype. Deletion of chromosomally encoded tolC also resulted in loss of the inhibitory phenotype, and this confirmed that the putative microcin is most likely secreted via a type I secretion pathway. Deletion of an unrelated plasmid gene did not affect the PDI phenotype. Quantitative reverse transcription (RT) PCR demonstrated that microcin expression is correlated with logarithmic-phase growth. The ability to inhibit a diversity of E. coli strains indicates that this microcin may influence gut community composition and could be useful for control of important enteric pathogens. PMID- 22773654 TI - Significance of the bacteriophage treatment schedule in reducing Salmonella colonization of poultry. AB - Salmonella remains the major cause of food-borne diseases worldwide, with chickens known to be the main reservoir for this zoonotic pathogen. Among the many approaches to reducing Salmonella colonization of broilers, bacteriophage offers several advantages. In this study, three bacteriophages (UAB_Phi20, UAB_Phi78, and UAB_Phi87) obtained from our collection that exhibited a broad host range against Salmonella enterica serovar Enteritidis and Salmonella enterica serovar Typhimurium were characterized with respect to morphology, genome size, and restriction patterns. A cocktail composed of the three bacteriophages was more effective in promoting the lysis of S. Enteritidis and S. Typhimurium cultures than any of the three bacteriophages alone. In addition, the cocktail was able to lyse the Salmonella enterica serovars Virchow, Hadar, and Infantis. The effectiveness of the bacteriophage cocktail in reducing the concentration of S. Typhimurium was tested in two animal models using different treatment schedules. In the mouse model, 50% survival was obtained when the cocktail was administered simultaneously with bacterial infection and again at 6, 24, and 30 h postinfection. Likewise, in the White Leghorn chicken specific pathogen-free (SPF) model, the best results, defined as a reduction of Salmonella concentration in the chicken cecum, were obtained when the bacteriophage cocktail was administered 1 day before or just after bacterial infection and then again on different days postinfection. Our results show that frequent treatment of the chickens with bacteriophage, and especially prior to colonization of the intestinal tract by Salmonella, is required to achieve effective bacterial reduction over time. PMID- 22773655 TI - Mercury resistance and mercuric reductase activities and expression among chemotrophic thermophilic Aquificae. AB - Mercury (Hg) resistance (mer) by the reduction of mercuric to elemental Hg is broadly distributed among the Bacteria and Archaea and plays an important role in Hg detoxification and biogeochemical cycling. MerA is the protein subunit of the homodimeric mercuric reductase (MR) enzyme, the central function of the mer system. MerA sequences in the phylum Aquificae form the deepest-branching lineage in Bayesian phylogenetic reconstructions of all known MerA homologs. We therefore hypothesized that the merA homologs in two thermophilic Aquificae, Hydrogenobaculum sp. strain Y04AAS1 (AAS1) and Hydrogenivirga sp. strain 128-5-R1 1 (R1-1), specified Hg resistance. Results supported this hypothesis, because strains AAS1 and R1-1 (i) were resistant to >10 MUM Hg(II), (ii) transformed Hg(II) to Hg(0) during cellular growth, and (iii) possessed Hg-dependent NAD(P)H oxidation activities in crude cell extracts that were optimal at temperatures corresponding with the strains' optimal growth temperatures, 55 degrees C for AAS1 and 70 degrees C for R1-1. While these characteristics all conformed with the mer system paradigm, expression of the Aquificae mer operons was not induced by exposure to Hg(II) as indicated by unity ratios of merA transcripts, normalized to gyrA transcripts for hydrogen-grown AAS1 cultures, and by similar MR specific activities in thiosulfate-grown cultures with and without Hg(II). The Hg(II)-independent expression of mer in the deepest-branching lineage of MerA from bacteria whose natural habitats are Hg-rich geothermal environments suggests that regulated expression of mer was a later innovation likely in environments where microorganisms were intermittently exposed to toxic concentrations of Hg. PMID- 22773656 TI - Acute ill-health in sheep farmers following use of pesticides. AB - BACKGROUND: Sheep farmers often complain of acute ill-health, known colloquially as 'dipper's flu', immediately after treating sheep with pesticides. There have been few prospective epidemiological studies to determine it's nature and incidence. Aims To determine the nature and frequency of symptoms occurring in farmers treating sheep for ectoparasites. METHODS: In a longitudinal study, farmers who planned to treat their sheep for ectoparasites were recruited. Farmers kept a symptom diary for 7 days after starting pesticide treatment. Symptoms reported on days 1-6 were compared to those reported on day 7 via the McNemar's test and with previously published literature definitions of dipper's flu. A principal component analysis (PCA) was carried out on new symptoms occurring on days 1 and 2. RESULTS: Of 781 farmers recruited, 352 farmers (45%) completed the symptom diary. In the 7 days after starting pesticide treatment, symptom complex reporting typically peaked on day 2, but few farmers (7 or less; <2%) were identified as having dipper's flu using literature definitions. However, PCA identified two new patterns of symptom complexes that accounted for 35% of the variance. A pyrexial factor consisted of four symptom complexes (feeling generally ill; feeling sweaty, shivery, feverish, hot or cold; feeling unusually tired; and having a headache) and a respiratory factor consisted of three symptom complexes (runny, stuffy, blocked or irritated nose; cough, shortness of breath or wheeze; and eye irritation). CONCLUSIONS: Existing definitions of dipper's flu do not adequately describe symptoms that occur following the treatment of sheep for ectoparasites. PMID- 22773657 TI - Vaccinating health care workers during an influenza pandemic. AB - BACKGROUND: In response to the 2009 H1N1 influenza pandemic, health care workers (HCWs) were offered immunization with H1N1 vaccine in addition to seasonal flu vaccine. Previously, low rates of influenza vaccine uptake in HCWs have been attributed to concerns about vaccine clinical effectiveness, side effects and access difficulties. AIMS: To explore H1N1 influenza vaccination of HCWs in London during 2009-10 and examine reasons for vaccine refusal. METHODS: An online questionnaire survey of doctors and nurses working in two primary care trust (PCT) areas and one acute trust area was carried out in London. RESULTS: Only 59% of the 221 respondents had been immunized with H1N1 influenza vaccine and 43% with seasonal influenza vaccine. The commonest reasons for remaining unvaccinated were 'side effects', 'swine flu not severe' and 'concerns about clinical effectiveness of the vaccine'. Respondents who had been vaccinated that season gave positive feedback on their experience. CONCLUSIONS: While uptake among HCWs was greater for the pandemic vaccine than is usually seen with seasonal influenza vaccine, this survey suggests that in this area of London during the 2009 pandemic, HCWs refused H1N1 vaccination due to concerns about clinical effectiveness, side effects and perceptions that H1N1 infection was not generally severe. We found no evidence to suggest poor access was a barrier to H1N1 vaccination of HCWs. If good access is maintained, the key barrier to improving seasonal flu vaccine uptake lies with informing the personal risk assessment made by the HCW. PMID- 22773658 TI - Biomarkers of ambient air pollution and lung cancer: a systematic review. AB - The association between ambient air pollution exposure and lung cancer risk has been investigated in prospective studies and the results are generally consistent, indicating that long-term exposure to air pollution may cause lung cancer. Despite the prospective nature and consistent findings of these studies, causality assessment can benefit from biomarker research. In the present systematic review, we assess the contribution of intermediate biomarkers in epidemiological studies, to ascertain whether their measurement reinforces causal reasoning. We have reviewed 524 papers which described the relationships between ambient air pollution and biological markers of dose and early response. The evidence for each marker was evaluated using assessment criteria which rate a group of studies from A (strong) to C (weak) on amount of evidence, replication of findings, and protection from bias. Biomarkers that scored A or B for all three criteria are included here. The markers that fulfilled the inclusion criteria are: 1-hydroxypyrene, DNA adducts, chromosomal aberrations, micronuclei, oxidative damage to nucleobases, and methylation changes. These biomarkers cover the whole spectrum of disease onset and progression from external exposure to tumour formation and some have also been suggested as risk predictors of future cancer, reinforcing causal reasoning. However, methodological issues such as confounding, publication bias and use of surrogate tissues instead of target tissues in studies on these markers are of concern. The identified biological markers have potential to shed light on the pathways of carcinogenesis, thus defining the association more clearly for public health interventions. PMID- 22773659 TI - Comment on "Inflammasome activation of IL-18 results in endothelial progenitor cell dysfunction in systemic lupus erythematosus". PMID- 22773660 TI - Comment on "Expression of Helios in peripherally induced Foxp3+ regulatory T cells". PMID- 22773661 TI - Comment on "Class B scavenger receptor types I and II and CD36 targeting improves sepsis survival and acute outcomes in mice". PMID- 22773662 TI - B cell tolerance and positive selection in lupus. AB - Systemic lupus erythematosus is considered a prototype of systemic autoimmune diseases; however, despite considerable advances in recent years in the understanding of basic mechanisms in immunology, little progress has been made in elucidating the etiology and pathogenesis of this disease. This even holds for inbred mice, such as the lupus-prone New Zealand Black/New Zealand White F(1) mice, which are all genetically programmed to develop lupus at a predetermined age. This frustrating state of affairs calls for a fundamental change in our scientific thinking and the opening of new directions in lupus research. In this study, we suggest that intrinsic B cell tolerance mechanisms are not grossly impaired in lupus-prone mice, but that an unusually strong positive selection event recruits a small number of autoreactive B cells to the germinal centers. This event could be facilitated by nucleic acid-protein complexes that are created by somatic changes in the susceptible animal. PMID- 22773663 TI - Glutamine deprivation enhances antitumor activity of 3-bromopyruvate through the stabilization of monocarboxylate transporter-1. AB - Anticancer drug efficacy might be leveraged by strategies to target certain biochemical adaptations of tumors. Here we show how depriving cancer cells of glutamine can enhance the anticancer properties of 3-bromopyruvate, a halogenated analog of pyruvic acid. Glutamine deprival potentiated 3-bromopyruvate chemotherapy by increasing the stability of the monocarboxylate transporter-1, an effect that sensitized cells to metabolic oxidative stress and autophagic cell death. We further elucidated mechanisms through which resistance to chemopotentiation by glutamine deprival could be circumvented. Overall, our findings offer a preclinical proof-of-concept for how to employ 3-bromopyruvate or other monocarboxylic-based drugs to sensitize tumors to chemotherapy. PMID- 22773665 TI - BMP4 administration induces differentiation of CD133+ hepatic cancer stem cells, blocking their contributions to hepatocellular carcinoma. AB - CD133+ cancer stem cells (CSC) contribute to hepatocellular carcinoma (HCC) progression and resistance to therapy. Bone morphogenetic protein BMP4 plays an important role in hepatogenesis and hepatic stem cell differentiation, but little is known about its function in hepatic CSCs. In this study, we showed that high dose exogenous BMP4 promotes CD133+ HCC CSC differentiation and inhibits the self renewal, chemotherapeutic resistance, and tumorigenic capacity of these cells. Interestingly, we found that low-dose exogenous BMP4 upregulated CD133 protein expression in vitro, and endogenous BMP4 was preferentially expressed in CD133+ HCC CSCs, suggesting that low doses of BMP4 may facilitate CSC maintenance. A reduction in endogenous BMP4 levels decreased CD133 protein expression in vitro. In HCC tissues, expression of the BMP4 signaling target gene SMAD6 was positively correlated with CD133 expression. Activation of the Erk1/2 signaling pathway led to BMP4-mediated reduction in CD133 expression, which was reversed by treatment with MEK inhibitors. Taken together, our findings indicated that BMP4 might be a potent therapeutic agent in HCC that targets CSCs. PMID- 22773664 TI - Concomitant targeting of tumor cells and induction of T-cell response synergizes to effectively inhibit trastuzumab-resistant breast cancer. AB - Trastuzumab is an iconic rationally designed targeted therapy for HER2-positive breast cancers. However, the low response rate and development of resistance call for novel approaches for the treatment of patients. Here, we report that concurrent targeting of tumor cells and activation of T cells in the tumor microenvironment results in a synergistic inhibitory effect on tumor growth and overcomes resistance in two distinct PTEN loss-mediated trastuzumab-resistant mammary tumor mouse models. In vivo combination treatment with HER2/Neu antibody and Akt inhibitor triciribine effectively inhibited tumor growth in both models via inhibiting PI3K/AKT and mitogen-activated protein kinase signaling accompanied by increased T-cell infiltration in the tumor microenvironment. We showed that both CD8(+) and CD4(+) T cells were essential to the optimal antitumor effect of this combination treatment in an IFN-gamma-dependent manner. Importantly, the antitumor activities of HER2/Neu antibody and triciribine combination treatment were further improved when coinhibitory receptor cytotoxic T-lymphocyte-associated antigen 4 was blocked to enhance the T-cell response. Our data indicate that multitargeted combinatorial therapies targeting tumor cells and concomitantly enhancing T-cell response in the tumor microenvironment could cooperate to exert maximal therapeutic activity, suggesting a promising clinical strategy for treating trastuzumab-resistant breast cancers and other advanced malignancies. PMID- 22773666 TI - Death protein 5 and p53-upregulated modulator of apoptosis mediate the endoplasmic reticulum stress-mitochondrial dialog triggering lipotoxic rodent and human beta-cell apoptosis. AB - Environmental factors such as diets rich in saturated fats contribute to dysfunction and death of pancreatic beta-cells in diabetes. Endoplasmic reticulum (ER) stress is elicited in beta-cells by saturated fatty acids. Here we show that palmitate-induced beta-cell apoptosis is mediated by the intrinsic mitochondrial pathway. By microarray analysis, we identified a palmitate-triggered ER stress gene expression signature and the induction of the BH3-only proteins death protein 5 (DP5) and p53-upregulated modulator of apoptosis (PUMA). Knockdown of either protein reduced cytochrome c release, caspase-3 activation, and apoptosis in rat and human beta-cells. DP5 induction depends on inositol-requiring enzyme 1 (IRE1)-dependent c-Jun NH2-terminal kinase and PKR-like ER kinase (PERK)-induced activating transcription factor (ATF3) binding to its promoter. PUMA expression is also PERK/ATF3-dependent, through tribbles 3 (TRB3)-regulated AKT inhibition and FoxO3a activation. DP5(-/-) mice are protected from high fat diet-induced loss of glucose tolerance and have twofold greater pancreatic beta-cell mass. This study elucidates the crosstalk between lipotoxic ER stress and the mitochondrial pathway of apoptosis that causes beta-cell death in diabetes. PMID- 22773667 TI - Cytotoxic mechanisms employed by mouse T cells to destroy pancreatic beta-cells. AB - Several cytotoxic mechanisms have been attributed to T cells participating in beta-cell death in type 1 diabetes. However, sensitivity of beta-cells to these mechanisms in vitro and in vivo is likely to be different. Moreover, CD4+ and CD8+ T cells may use distinct mechanisms to cause beta-cell demise that possibly involve activation of third-party cytotoxic cells. We used the transfer of genetically modified diabetogenic T cells into normal, mutant, and bone marrow chimeric recipients to test the contribution of major cytotoxic mechanisms in beta-cell death. We found that 1) the killing of beta-cells by CD4+ T cells required activation of the recipient's own cytotoxic cells via tumor necrosis factor-alpha (TNF-alpha); 2) CD8+ T-cell cytotoxic mechanisms destroying beta cells were limited to perforin and Fas ligand, as double knockouts of these molecules abrogated the ability of T cells to cause diabetes; and 3) individual CD8+ T-cell clones chose their cytotoxic weaponry by a yet unknown mechanism and destroyed their targets via either Fas-independent or Fas-dependent (~40% of clones) pathways. Fas-dependent destruction was assisted by TNF-alpha. PMID- 22773668 TI - Orthodontics in the 21st century: a view from across the pond. PMID- 22773670 TI - Enamel colour changes after debonding using various bonding systems. AB - OBJECTIVE: To test the possible association between enamel colour alteration and resin tag depth. DESIGN: In vitro laboratory study. SETTING: Department of Orthodontics, Alexandria University, Egypt. MATERIALS AND METHODS: Fifty freshly extracted human premolar teeth were equally divided randomly into a control and four experimental groups. Teeth in group I received only enamel prophylaxis. Teeth in groups II and III were etched with 35% phosphoric acid for 15 and 60 seconds, respectively. Teeth in group IV were conditioned with Prompt L-pop self etching primer and in group V with Xeno III self-etching primer, according to the manufacturer's instructions. Orthodontic brackets were bonded to the teeth in all experimental groups using Transbond XT composite. Following bracket debonding, finishing and polishing were performed. Enamel colour was evaluated spectrophotometrically at baseline and then after debonding, with the corresponding colour differences DeltaE calculated. Resin tags lengths were measured on sectioned teeth in each experimental group under scanning electron microscope. RESULTS: All experimental groups showed clinically perceivable colour change after debonding and finishing as all values were exceeded the clinical colour detection threshold of DeltaE = 3.7 units. Significant differences (P<0.05) in resin tag length were found in all experimental groups. Significant moderate correlation was found between colour change and resin tags length when all teeth were combined and tested, irrespective of group. CONCLUSIONS: Moderate evidence exists that shorter resin tag penetration produces less change in enamel colour following clean-up and polishing. Self-etch primers produce less resin penetration and these systems may produce less iatrogenic colour change in enamel following orthodontic treatment. PMID- 22773671 TI - Investigation of the transmigrated canine in an orthodontic patient population. AB - OBJECTIVE: To investigate the prevalence, demographic and clinical characteristics of transmigrated canines in a south Indian orthodontic patient population. DESIGN: Retrospective observational study. SETTING: Manipal University, Manipal, India. SUBJECTS AND METHODS: Panoramic radiographs of 3500 patients were examined and data collected regarding the number and side of transmigrated canines, sex and age of patients, any other associated pathologies and subsequent treatment. Transmigrated canines were classified according to Mupparapu's classification. RESULTS: The prevalence of transmigrated canines in this population was found to be 0.46% of which, seven were males (age: 17-51 years) and nine were females (age: 17-35 years). All transmigrated canines were unilateral and impacted. Eleven canines migrated from the left to the right side, and five migrated from the right to the left. Of the 16 patients, 13 had retained primary canines and 3 had exfoliated primary canines. Eight canines exhibited a type 1 transmigratory pattern, type 2, type 4 and type 5 transmigratory patterns were exhibited by two canines each. One of the canines was classified as type 3. Three canines were associated with dentigerous cyst formation. Four cases were treated by orthodontic traction, while one was removed surgically. Others were observed periodically. CONCLUSIONS: Diagnosis of transmigration at earlier stages is important to prevent more complex occlusal problems. PMID- 22773672 TI - The effects of facemask and reverse chin cup on maxillary deficient patients. AB - INTRODUCTION: The aim of this randomized clinical trial was to assess differences in the effects of face mask and reverse chin cup therapy on maxillary deficient growing patients. METHODS: The sample consisted of 42 class III patients with maxillary deficiency randomly divided into two equal groups. Twenty-one patients (10 males and 11 females) with a mean age of 8.9 (SD: 1.4) years were treated with a face mask for 18 (SD: 2) months. Twenty-one patients (9 males and 12 females) with the mean age of 9.2 (SD: 1.1) years were treated with a reverse chin cup for 19 (SD: 4) months. Cephalometric radiographs were taken at the beginning and end of treatment and the cephalometric measurements were analysed. Paired t-tests and a Wilcoxon test were used for intra-group evaluations. Mann Whitney test was used for inter-group evaluations. RESULTS: Sella-Nasion-A point (SNA) was increased by 1 degrees (SD: 1.7 degrees ) (P<0.003) and 1.8 degrees (SD: 1.7 degrees ) (P<0.001) in the face mask and reverse chin cup groups, respectively. The IMPA decreased by 4.1 degrees (SD: 6.5 degrees ) in face mask group (P<0.009) and 3.1 degrees (SD: 4.7 degrees ) in the reverse chin cup group (P<0.008). However, no statistically significant differences were seen in changes between the two groups. CONCLUSION: Both face mask and reverse chin cup appliances are successful at moving the maxilla forward. PMID- 22773673 TI - Mini-screw implant or transpalatal arch-mediated anchorage reinforcement during canine retraction: a randomized clinical trial. AB - OBJECTIVE: To compare mesial movement of upper first molars during maxillary canine retraction using a pre-adjusted edgewise appliance provided by anchorage reinforcement and a transpalatal arch or mini-screw implant. DESIGN: Randomized clinical trial. SETTING: Department of Orthodontics and Dentofacial Orthopedics, Armed Forces Medical College, Pune, India. SUBJECTS AND METHODS: From a cohort of subjects requiring the extraction of both upper first premolars and pre-adjusted edgewise appliances to correct their malocclusion, a total of 30 were randomly allocated to receive two different forms of anchorage reinforcement: group A- receiving mini-screw implant and group B--receiving a transpalatal arch Group A subjects received titanium mini-screw implants placed at the start of treatment between the maxillary second premolar and maxillary first molar. Maxillary second premolars were secured to the mini-screw implants using of 0.010-inch stainless steel ligature wire. Group B subjects received a custom-made transpalatal arch which was soldered to maxillary first molar bands. Active canine retraction was initiated in both groups on placement of a 0.019*0.025-inch stainless steel archwire using nickel titanium closed coil springs. OUTCOME MEASURES: Mesial movement of the upper first molars as measured on pre- (T1) and post-treatment (T2) lateral skull radiographs. RESULTS: The results showed that in group A the mean mesial movement of the first molars between T1 and T2 was 0.0 mm (SD 0.02; P = 0.90), whereas in Group B there was a mean forward movement of the first maolars of 2.48 mm (SD 0.71; P<0.001). CONCLUSION: In this trial, mini-screw implants placed prior to levelling and aligning were able to provide absolute anchorage during maxillary canine retraction, in contrast to a transpalatal arch. PMID- 22773674 TI - Comparison of deactivation forces between thermally activated nickel-titanium archwires. AB - OBJECTIVE: The aim of the present study was to investigate and compare load deflection characteristics of commercially available thermally activated nickel titanium archwires using a three-point bending test. MATERIALS AND METHODS: Sixty thermally activated 0.019*0.025-inch nickel-titanium archwires from six different manufacturers were investigated. The superelastic properties of these archwires were evaluated by conducting a three-point bending test under identical testing conditions. Forces generated at deactivation for a deflection of 0.5, 1, 2 and 3 mm at a temperature of 37 degrees C were selected for statistical comparison of the data. The results of forces of deactivation at all deflections applied were compared by two-way analysis of variance and the Tukey test. RESULTS: Statistical differences (P<0.05) were found at all force levels during deactivations. The results showed that the range of forces displayed great variation in quantitative behaviour. None of the archwires showed permanent deformation after the three point bending test. CONCLUSIONS: This study revealed significant differences in deactivation forces among the six types of thermally activated nickel-titanium archwires tested. NiTinol Termoativado (Aditek) and NeoSentalloy F200 (GAC) produced the least amount of force in all four deactivation categories. PMID- 22773675 TI - Coronectomy for infraoccluded lower first permanent molars: a report of two cases. AB - Two cases of infraoccluded lower first permanent molars were treated at Glasgow Dental Hospital and School with a joint orthodontic and surgical approach. Coronectomy, a technique usually reserved for deeply impacted lower third molars, was carried out in both cases; these are discussed. PMID- 22773676 TI - Accelerated osteogenic orthodontics--a case report. AB - This case report outlines the possibility of rapid orthodontic tooth movement with the use of an accelerated osteogenic technique. A 28-year-old female patient presented with a class I malocclusion, bimaxillary proclination, spacing between the maxillary and mandibular incisors and previous extraction of all four first premolars. Orthodontic treatment from appliance placement to debond took 6 months and 2 weeks. PMID- 22773677 TI - Bonded molar tubes: a survey of their use by specialist orthodontists. AB - OBJECTIVE: To investigate the use of bonded molar tubes (BMTs) by specialist orthodontists. DESIGN: Prospective postal questionnaire. SETTING: Ireland. PARTICIPANTS: Registered members of the Orthodontic Society of Ireland. METHODS: A questionnaire was posted to registered members of the Orthodontic Society of Ireland. It investigated demographics, pattern of use, reasons for use and techniques for placement of BMTs. RESULTS: A 74% response rate was obtained. In more than 80% of cases, BMTs were used on first and second permanent molars by 52% and 33% of orthodontists respectively. BMT usage was adopted by 97% of respondents in the previous decade. Direct bonding was used by all for BMT placement. Etch times for molars, compared to other teeth, increased from 15 to 30 seconds by 51% of orthodontists. Of the respondents, 97% used light-cured adhesives and 17% used self-etching primers. Molar tube holders were preferred by 54% for placement. Only with a history of epilepsy, were bands preferred to BMTs. BMTs were regarded as more cost-effective than molar bands by 66% of responding clinicians. CONCLUSIONS: Specialist orthodontists preferred BMTs to bands on first permenent molars. Direct bonding was favoured using a 30-second etch, a light-cured primer and adhesive with specialized molar tube holders. BMTs were perceived to be more cost-effective than molar bands. PMID- 22773680 TI - Plenary perspective: the complexity of constitutive and inducible gene expression in mononuclear phagocytes. AB - Monocytes and macrophages differentiate from progenitor cells under the influence of colony-stimulating factors. Genome-scale data have enabled the identification of the set of genes that distinguishes macrophages from other cell types and the ways in which thousands of genes are regulated in response to pathogen challenge. Although there has been a focus on a small subset of lineage-enriched transcription factors, such as PU.1, more than one-half of the transcription factors in the genome can be expressed in macrophage lineage cells under some state of activation, and they interact in a complex network. The network architecture is conserved across species, but many of the target genes evolve rapidly and differ between mouse and human. The data and publication deluge related to macrophage biology require the development of new analytical tools and ways of presenting information in an accessible form. PMID- 22773681 TI - UV-B irradiation changes specifically the secondary metabolite profile in broccoli sprouts: induced signaling overlaps with defense response to biotic stressors. AB - Only a few environmental factors have such a pronounced effect on plant growth and development as ultraviolet light (UV). Concerns have arisen due to increased UV-B radiation reaching the Earth's surface as a result of stratospheric ozone depletion. Ecologically relevant low to moderate UV-B doses (0.3-1 kJ m(-2) d( 1)) were applied to sprouts of the important vegetable crop Brassica oleracea var. italica (broccoli), and eco-physiological responses such as accumulation of non-volatile secondary metabolites were related to transcriptional responses with Agilent One-Color Gene Expression Microarray analysis using the 2*204 k format Brassica microarray. UV-B radiation effects have usually been linked to increases in phenolic compounds. As expected, the flavonoids kaempferol and quercetin accumulated in broccoli sprouts (the aerial part of the seedlings) 24 h after UV B treatment. A new finding is the specific UV-B-mediated induction of glucosinolates (GS), especially of 4-methylsulfinylbutyl GS and 4-methoxy-indol-3 ylmethyl GS, while carotenoids and Chl levels remained unaffected. Accumulation of defensive GS metabolites was accompanied by increased expression of genes associated with salicylate and jasmonic acid signaling defense pathways and up regulation of genes responsive to fungal and bacterial pathogens. Concomitantly, plant pre-exposure to moderate UV-B doses had negative effects on the performance of the caterpillar Pieris brassicae (L.) and on the population growth of the aphid Myzus persicae (Sulzer). Moreover, insect-specific induction of GS in broccoli sprouts was affected by UV-B pre-treatment. PMID- 22773683 TI - The prediction of adverse cardiac remodelling following myocardial infarction: defining the need for a dynamic multimarker approach. PMID- 22773682 TI - The involvement of Arabidopsis glutathione peroxidase 8 in the suppression of oxidative damage in the nucleus and cytosol. AB - A family of eight genes with homology to mammalian glutathione peroxidase (GPX) isoenzymes, designated AtGPX1-AtGPX8, has been identified in Arabidopsis thaliana. In this study we demonstrated the functional analysis of Arabidopsis AtGPX8 with peroxidase activity toward H(2)O(2) and lipid hydroperoxides using thioredoxin as an electron donor. The transcript and protein levels of AtGPX8 in Arabidopsis were up-regulated coordinately in response to oxidative damage caused by high-light (HL) stress or treatment with paraquat (PQ). Furthermore, the knockout Arabidopsis mutants of AtGPX8 (KO-gpx8) exhibited increased sensitivity to oxidative damage caused by PQ treatment in root elongation compared with the wild-type plants. In contrast, transgenic lines overexpressing AtGPX8 (Ox-AtGPX8) were less sensitive to oxidative damage than the wild-type plants. The levels of oxidized proteins in the KO-gpx8 and Ox-AtGPX8 lines were enhanced and suppressed, respectively, compared with the wild-type plants under HL stress or PQ treatment. The fusion protein of AtGPX8 tagged with green fluorescent protein was localized in the cytosol and nucleus of onion epidermal cells. In addition, the AtGPX8 protein was detected in the cytosolic and nuclear fractions prepared from leaves of Arabidopsis plants using the AtGPX8 antibody. Oxidative DNA damage under treatment with PQ increased in the wild-type and KO-gpx8 plants, while it decreased in the OX-AtGPX8 plants. These results suggest that AtGPX8 plays an important role in the protection of cellular components including nuclear DNA against oxidative stress. PMID- 22773684 TI - Accuracy of aortic annular measurements obtained from three-dimensional echocardiography, CT and MRI: human in vitro and in vivo studies. AB - OBJECTIVES: To determine the accuracy of calcium-containing rings measurements imaged by three-dimensional echocardiography (3DE), multi-slice CT (MSCT) and cardiac magnetic resonance (CMR) under ideal conditions against the true ring dimensions. To compare the accuracy of aortic annulus (AoA) measurements in ex vivo human hearts using 3DE, MSCT and CMR. To determine the accuracy of AoA measurements in an in vivo human model. DESIGN: 3DE, MSCT and CMR imaging were performed on 30 calcium-containing rings and 28 explanted human hearts. Additionally, 15 human subjects with clinical indication for MSCT underwent 3DE. Two experts in each modality measured the images. MAIN OUTCOME MEASURES: Bias and intraclass correlation coefficient for accuracy of imaging measurements when compared with actual ring dimensions. Bias, intraclass correlation coefficient and variability were obtained: (1) when comparing explanted human heart AoA measurements from the two remaining imaging modalities with the most accurate one as determined from the ring measurements and (2) in in vivo human AoA measurements. Analysis was repeated on explanted heart subgroups divided by aortic valve Agatston score. RESULTS: Against the known ring dimensions, CMR had the highest accuracy and the lowest variability. MSCT measurements had high accuracy but wider variability and 3DE had the lowest accuracy with the largest variability. When 3DE and MSCT were compared with CMR, 3DE underestimated and MSCT overestimated AoA dimensions, but inter-measurement variability of 3DE and MSCT were similar. When divided by Agatston score, both 3DE and MSCT measurements were larger and showed greater variability with increasing calcium burden. The in vivo study showed that the correlation between 3DE and MSCT measurements was high; however, 3DE measurements were smaller than those measured with MSCT. CONCLUSIONS: In the in vitro model, CMR measurements were the most accurate for assessing the actual dimensions suggesting that further investigations on its role in AoA measurement in TAVR are needed. However from the in vivo model, MSCT and 3DE are reasonable alternatives with the understanding that they can slightly overestimate and underestimate annular dimensions, respectively. PMID- 22773685 TI - How to establish video assisted, minimally invasive mitral valve surgery. PMID- 22773687 TI - Effects of Therapeutic Lifestyle Change diets high and low in dietary fish derived FAs on lipoprotein metabolism in middle-aged and elderly subjects. AB - The effects of Therapeutic Lifestyle Change (TLC) diets, low and high in dietary fish, on apolipoprotein metabolism were examined. Subjects were provided with a Western diet for 6 weeks, followed by 24 weeks of either of two TLC diets (10/group). Apolipoprotein kinetics were determined in the fed state using stable isotope methods and compartmental modeling at the end of each phase. Only the high-fish diet decreased median triglyceride-rich lipoprotein (TRL) apoB-100 concentration (-23%), production rate (PR, -9%), and direct catabolism (-53%), and increased TRL-to-LDL apoB-100 conversion (+39%) as compared with the baseline diet (all P < 0.05). This diet also decreased TRL apoB-48 concentration (-24%), fractional catabolic rate (FCR, -20%), and PR (-50%) as compared with the baseline diet (all P < 0.05). The high-fish and low-fish diets decreased LDL apoB 100 concentration (-9%, -23%), increased LDL apoB-100 FCR (+44%, +48%), and decreased HDL apoA-I concentration (-15%, -14%) and PR (-11%, -12%) as compared with the baseline diet (all P < 0.05). On the high-fish diet, changes in TRL apoB 100 PR were negatively correlated with changes in plasma eicosapentaenoic and docosahexaenoic acids. In conclusion, the high-fish diet decreased TRL apoB-100 and TRL apoB-48 concentrations chiefly by decreasing their PR. Both diets decreased LDL apoB-100 concentration by increasing LDL apoB-100 FCR and decreased HDL apoA-I concentration by decreasing HDL apoA-I PR. PMID- 22773688 TI - Raft-like microdomains play a key role in mitochondrial impairment in lymphoid cells from patients with Huntington's disease. AB - Huntington's disease (HD) is a genetic neurodegenerative disease characterized by an exceedingly high number of contiguous glutamine residues in the translated protein, huntingtin (Htt). The primary site of cell toxicity is the nucleus, but mitochondria have been identified as key components of cell damage. The present work has been carried out in immortalized lymphocytes from patients with HD. These cells, in comparison with lymphoid cells from healthy subjects, displayed: i) a redistribution of mitochondria, forming large aggregates; ii) a constitutive hyperpolarization of mitochondrial membrane; and iii) a constitutive alteration of mitochondrial fission machinery, with high apoptotic susceptibility. Moreover, mitochondrial fission molecules, e.g., protein dynamin-related protein 1, as well as Htt, associated with mitochondrial raft-like microdomains, glycosphingolipid enriched structures detectable in mitochondria. These findings, together with the observation that a ceramide synthase inhibitor and a raft disruptor are capable of impairing the peculiar mitochondrial remodeling in HD cells, suggest that mitochondrial alterations occurring in these cells could be due to raft-mediated defects of mitochondrial fission/fusion machinery. PMID- 22773689 TI - Quantitation of lysolipids, fatty acids, and phospholipase A2 activity and correlation with membrane polarity. AB - Acrylodan-labeled rat-intestinal fatty acid binding protein, ADIFAB, binds both of lysophosphatidylcholines (LPC) and FA. Binding displaces Acrylodan and its fluorescence peak shifts from 432 to 505 nm. A fluorescence assay that relies on this shift is presented for quantitating LPC, FA, and phospholipase A(2) (PLA(2)) activity in phospholipid bilayers in absolute units of MUM/min/mg of enzyme. This is a development over an earlier assay that took into account only FA binding. Activities of bee venom PLA(2) on dipalmitoylphosphatidylcholine (DPPC) and dioleylphosphatidylcholine (DOPC) bilayers were measured. Standard pH-Stat assays validated the present assay. Products increase linearly with time for about one minute in DOPC and five minutes in DPPC corresponding to completion of 5 to 8% hydrolysis in DOPC and 20% in DPPC. Membrane polarity and microviscosity measured using electron spin resonance (ESR) exhibited discontinuities at compositions that mimicked similar percentages of hydrolysis products in the respective bilayers. The observed hydrolysis rate decrease following the initial linear period thus correlates to changes in membrane polarity. The ability of the assay to yield actual product concentrations, reveal structure in the reaction progress curves, and interpretation in light of the ESR data bring insight into the shape of the reaction curve. PMID- 22773690 TI - IL-13-induced changes in endogenous glucocorticoid metabolism in the lung regulate the proasthmatic response. AB - Endogenous glucocorticoid (GC) activation is regulated by the intracellular GC activating and -inactivating enzymes 11beta-hydroxysteroid dehydrogenase (11beta HSD)1 and 11beta-HSD2, respectively, that catalyze interconversion of inert cortisone and its bioactive metabolite cortisol. Because endogenous GCs are critically implicated in suppressing the asthmatic state, this study examined the roles of the 11beta-HSD enzymes in regulating GC activation and bronchoprotection during proasthmatic stimulation. Airway hyperresponsiveness to methacholine and inflammation were assessed in rabbits following inhalation of the proasthmatic/proinflammatory cytokine IL-13 with and without pretreatment with the 11beta-HSD inhibitor carbenoxolone (CBX). Additionally, IL-13-induced changes in 11beta-HSD isozyme expression and GC metabolism were examined in epithelium intact and -denuded tracheal segments and peripheral lung tissues. Finally, the effects of pretreatment with CBX or 11beta-HSD2-targeted siRNAs were investigated with respect to cortisol prevention of IL-13-induced airway constrictor hyperresponsiveness and eotaxin-3 production by airway epithelial cells. IL-13 exposed rabbits exhibited airway hyperresponsiveness, inflammation, and elevated bronchoalveolar lung fluid levels of eotaxin-3. These responses were inhibited by pretreatment with CBX, suggesting a permissive proasthmatic role for 11beta-HSD2. Supporting this concept, extended studies demonstrated that 1) IL-13-treated tracheal epithelium and peripheral lung tissues exhibit upregulated 11beta-HSD2 activity, 2) the latter impairs cortisone-induced cortisol accumulation and the ability of administered cortisol to prevent both IL-13-induced heightened airway contractility and eotaxin-3 release from epithelial cells, and 3) these proasthmatic responses are prevented by cortisol administration in the presence of 11beta-HSD2 inhibition. Collectively, these data demonstrate that the proasthmatic effects of IL-13 are enabled by impaired endogenous GC activation in the lung that is attributed to upregulation of 11beta-HSD2 in the pulmonary epithelium. PMID- 22773691 TI - miR-140-3p regulation of TNF-alpha-induced CD38 expression in human airway smooth muscle cells. AB - CD38, a membrane protein expressed in airway smooth muscle (ASM) cells, plays a role in cellular Ca(2+) dynamics and ASM contractility. In human ASM (HASM) cells, TNF-alpha induces CD38 expression through activation of MAPKs, NF-kappaB, and AP-1, and its expression is differentially elevated in cells from asthmatic patients compared with cells from nonasthmatic subjects. The CD38 3'-untranslated region (UTR) has targets for miR-140-3p. We hypothesized that miR-140-3p regulates CD38 expression in HASM cells by altering CD38 mRNA stability. Basal and TNF-alpha-induced expression of miR-140-3p was determined in nonasthmatic ASM (NAASM) and asthmatic ASM (AASM) cells. NAASM and AASM cells were transfected with control, miR-140-3p mimic, or miR-140-3p antagomirs, and CD38 expression and CD38 mRNA stability were determined. Luciferase reporter assays were used to determine miR-140-3p binding to the CD38 3'-UTR. Activation of p38, ERK, and JNK MAPKs, NF-kappaB, and AP-1 was determined in miR-140-3p mimic-transfected NAASM. TNF-alpha attenuated miR-140-3p expression in NAASM and AASM cells, but at a greater magnitude in AASM cells. CD38 mRNA expression was attenuated by miR-140 3p mimic at comparable magnitude in NAASM and AASM cells. Mutated miR-140-3p target on the CD38 3'-UTR reversed the inhibition of luciferase activity by miR 140-3p mimic. CD38 mRNA stability was unaltered by miR-140-3p mimic in NAASM or AASM cells following arrest of transcription. TNF-alpha-induced activation of p38 MAPK and NF-kappaB was attenuated by miR-140-3p mimic. The findings indicate that miR-140-3p modulates CD38 expression in HASM cells through direct binding to the CD38 3'-UTR and indirect mechanisms involving activation of p38 MAPK and NF kappaB. Furthermore, indirect mechanisms appear to play a major role in the regulation of CD38 expression. PMID- 22773692 TI - Experimental Pneumocystis lung infection promotes M2a alveolar macrophage-derived MMP12 production. AB - Among several bacterial and viral pathogens, the atypical fungal organism Pneumocystis jirovecii has been implicated as a contributor to the pathogenesis of chronic obstructive pulmonary disease (COPD). In a previous study, we reported that Pneumocystis-colonized HIV-positive subjects had worse obstruction of airways and higher sputum levels of macrophage elastase/matrix metalloproteinase 12 (MMP12), a protease strongly associated with the development of COPD. Here, we examined parameters of Pneumocystis-induced MMP12 in the lungs of mice and its role in the lung immune response to murine Pneumocystis. Initial studies demonstrated that P. murina exposure induced Mmp12 mRNA expression in whole lungs and alveolar macrophages (AMs), which was dependent on the presence of CD4+ T cells as well as signal transducer and activator of transcription 6. Mmp12 mRNA expression was upregulated in AMs by interleukin (IL)-4 treatment, but downregulated by interferon (IFN)-gamma, indicating preferential expression in alternatively activated (M2a) macrophages. IL-4 treatment induced the 54-kDa proenzyme form of MMP12 and the 22-kDa fully processed and active form, whereas IFN-gamma failed to induce either. Despite a reported antimicrobial role in macrophage phagolysosomes, mice deficient in MMP12 were not found to be more susceptible to lung infection with P. murina. Collectively, our data indicate that MMP12 induction is a component of the P. murina-induced M2 response and thus provides insight into the link between Pneumocystis colonization/infection and exacerbations in COPD. PMID- 22773693 TI - Effect of nitric oxide on epithelial ion transports in noncystic fibrosis and cystic fibrosis human proximal and distal airways. AB - The airways of patients with cystic fibrosis (CF) exhibit decreased nitric oxide (NO) concentrations, which might affect airway function. The aim of this study was to determine the effects of NO on ion transport in human airway epithelia. Primary cultures of non-CF and CF bronchial and bronchiolar epithelial cells were exposed to the NO donor sodium nitroprusside (SNP), and bioelectric variables were measured in Ussing chambers. Amiloride was added to inhibit the Na(+) channel ENaC, and forskolin and ATP were added successively to stimulate cAMP- and Ca(2+)-dependent Cl(-) secretions, respectively. The involvement of cGMP was assessed by measuring the intracellular cGMP concentration in bronchial cells exposed to SNP and the ion transports in cultures exposed to 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one, an inhibitor of the soluble guanylate cyclase (ODQ), or to 8Z, a cocktail of 8-bromo-cGMP and zaprinast (phosphodiesterase 5 inhibitor). SNP decreased the baseline short-circuit current (I(sc)) and the changes in I(sc) induced by amiloride, forskolin, and ATP in non-CF bronchial and bronchiolar cultures. The mechanism of this inhibition was studied in bronchial cells. SNP increased the intracellular cGMP concentration ([cGMP](i)). The inhibitory effect of SNP was abolished by 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, an NO scavenger (PTIO) and ODQ and was partly mimicked by increasing [cGMP](i). In CF cultures, SNP did not significantly modify ion transport; in CF bronchial cells, 8Z had no effect; however, SNP increased the [cGMP](i). In conclusion, exogenous NO may reduce transepithelial Na(+) absorption and Cl(-) secretion in human non-CF airway epithelia through a cGMP-dependent pathway. In CF airways, the NO/cGMP pathway appears to exert no effect on transepithelial ion transport. PMID- 22773694 TI - Hypoxia sensitivity of a voltage-gated potassium current in porcine intrapulmonary vein smooth muscle cells. AB - Hypoxia contracts the pulmonary vein, but the underlying cellular effectors remain unclear. Utilizing contractile studies and whole cell patch-clamp electrophysiology, we report for the first time a hypoxia-sensitive K(+) current in porcine pulmonary vein smooth muscle cells (PVSMC). Hypoxia induced a transient contractile response that was 56 +/- 7% of the control response (80 mM KCl). This contraction required extracellular Ca(2+) and was sensitive to Ca(2+) channel blockade. Blockade of K(+) channels by tetraethylammonium chloride (TEA) or 4-aminopyridine (4-AP) reversibly inhibited the hypoxia-mediated contraction. Single-isolated PVSMC (typically 159.1 +/- 2.3 MUm long) had mean resting membrane potentials (RMP) of -36 +/- 4 mV with a mean membrane capacitance of 108 +/- 3.5 pF. Whole cell patch-clamp recordings identified a rapidly activating, partially inactivating K(+) current (I(KH)) that was hypoxia, TEA, and 4-AP sensitive. I(KH) was insensitive to Penitrem A or glyburide in PVSMC and had a time to peak of 14.4 +/- 3.3 ms and recovered in 67 ms following inactivation at +80 mV. Peak window current was -32 mV, suggesting that I(KH) may contribute to PVSMC RMP. The molecular identity of the potassium channel is not clear. However, RT-PCR, using porcine pulmonary artery and vein samples, identified Kv(1.5), Kv(2.1), and BK, with all three being more abundant in the PV. Both artery and vein expressed STREX, a highly conserved and hypoxia-sensitive BK channel variant. Taken together, our data support the hypothesis that hypoxic inhibition of I(KH) would contribute to hypoxic-induced contraction in PVSMC. PMID- 22773695 TI - Adenosine triphosphate regulates NADPH oxidase activity leading to hydrogen peroxide production and COX-2/PGE2 expression in A549 cells. AB - Non-small cell lung carcinoma (NSCLC) accounts for most of all lung cancers, which is the leading cause of mortality in human beings. High level of cyclooxygenase-2 (COX-2) is one of the features of NSCLC and related to the low survival rate of NSCLC. However, whether extracellular nucleotides releasing from stressed resident tissues contributes to the expression of COX-2 remains unclear. Here, we showed that stimulation of A549 cells by adenosine 5'-O-(3 thiotriphosphate) (ATPgammaS) led to an increase in COX-2 gene expression and prostaglandin E(2) (PGE(2)) synthesis, revealed by Western blotting, RT-PCR, promoter assay, and enzyme-linked immunosorbent assay. In addition, ATPgammaS induced intracellular reactive oxygen species (ROS) generation through the activation of NADPH oxidase. The increase of ROS level resulted in activation of the c-Src/epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor (NF)-kappaB cascade. We also found that activated Akt was translocated into the nucleus and recruited with NF-kappaB and p300 to form a complex. Thus, activation of p300 modulated the acetylation of histone H4 via the NADPH oxidase/c-Src/EGFR/PI3K/Akt/NF-kappaB cascade stimulated by ATPgammaS. Our results are the first to show a novel role of NADPH oxidase dependent Akt/p65/p300 complex formation that plays a key role in regulating COX 2/PGE(2) expression in ATPgammaS-treated A549 cells. Taken together, we demonstrated that ATPgammaS stimulated activation of NADPH oxidase, resulting in generation of ROS, which then activated the downstream c-Src/EGFR/PI3K/Akt/NF kappaB/p300 cascade to regulate the expression of COX-2 and synthesis of PGE(2) in A549 cells. Understanding the regulation of COX-2 expression and PGE(2) release by ATPgammaS on A549 cells may provide potential therapeutic targets of NSCLC. PMID- 22773696 TI - Glycogen synthase kinase-3beta/beta-catenin signaling regulates neonatal lung mesenchymal stromal cell myofibroblastic differentiation. AB - In bronchopulmonary dysplasia (BPD), alveolar septa are thickened with collagen and alpha-smooth muscle actin-, transforming growth factor (TGF)-beta-positive myofibroblasts. We examined the biochemical mechanisms underlying myofibroblastic differentiation, focusing on the role of glycogen synthase kinase-3beta (GSK 3beta)/beta-catenin signaling pathway. In the cytoplasm, beta-catenin is phosphorylated on the NH(2) terminus by constitutively active GSK-3beta, favoring its degradation. Upon TGF-beta stimulation, GSK-3beta is phosphorylated and inactivated, allowing beta-catenin to translocate to the nucleus, where it activates transcription of genes involved in myofibroblastic differentiation. We examined the role of beta-catenin in TGF-beta1-induced myofibroblastic differentiation of neonatal lung mesenchymal stromal cells (MSCs) isolated from tracheal aspirates of premature infants with respiratory distress. TGF-beta1 increased beta-catenin expression and nuclear translocation. Transduction of cells with GSK-3beta S9A, a nonphosphorylatable, constitutively active mutant that favors beta-catenin degradation, blocked TGF-beta1-induced myofibroblastic differentiation. Furthermore, transduction of MSCs with DeltaN-catenin, a truncation mutant that cannot be phosphorylated on the NH(2) terminus by GSK 3beta and is not degraded, was sufficient for myofibroblastic differentiation. In vivo, hyperoxic exposure of neonatal mice increases expression of beta-catenin in alpha-smooth muscle actin-positive myofibroblasts. Similar changes were found in lungs of infants with BPD. Finally, low-passage unstimulated MSCs from infants developing BPD showed higher phospho-GSK-3beta, beta-catenin, and alpha-actin content compared with MSCs from infants not developing this disease, and phospho GSK-3beta and beta-catenin each correlated with alpha-actin content. We conclude that phospho-GSK-3beta/beta-catenin signaling regulates alpha-smooth muscle actin expression, a marker of myofibroblast differentiation, in vitro and in vivo. This pathway appears to be activated in lung mesenchymal cells from patients with BPD. PMID- 22773697 TI - Mitochondrial DNA-depleted A549 cells are resistant to bleomycin. AB - Alveolar epithelial cells are considered to be the primary target of bleomycin induced lung injury, leading to interstitial fibrosis. The molecular mechanisms by which bleomycin causes this damage are poorly understood but are suspected to involve generation of reactive oxygen species and DNA damage. We studied the effect of bleomycin on mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) in human alveolar epithelial A549 cells. Bleomycin caused an increase in reactive oxygen species production, DNA damage, and apoptosis in A549 cells; however, bleomycin induced more mtDNA than nDNA damage. DNA damage was associated with activation of caspase-3, cleavage of poly(ADP-ribose) polymerase, and cleavage and activation of protein kinase D1 (PKD1), a newly identified mitochondrial oxidative stress sensor. These effects appear to be mtDNA-dependent, because no caspase-3 or PKD1 activation was observed in mtDNA-depleted (rho(0)) A549 cells. Survival rate after bleomycin treatment was higher for A549 rho(0) than A549 cells. These results suggest that A549 rho(0) cells are more resistant to bleomycin toxicity than are parent A549 cells, likely in part due to the depletion of mtDNA and impairment of mitochondria-dependent apoptotic pathways. PMID- 22773699 TI - Antenatal diagnosis of fetal genotype determines if maternal hyperglycemia due to a glucokinase mutation requires treatment. AB - OBJECTIVE: In women with hyperglycemia due to heterozygous glucokinase (GCK) mutations, the fetal genotype determines its growth. If the fetus inherits the mutation, birth weight is normal when maternal hyperglycemia is not treated, whereas intensive treatment may adversely reduce fetal growth. However, fetal genotype is not usually known antenatally, making treatment decisions difficult. HISTORY AND EXAMINATION: We report two women with gestational diabetes mellitus resulting from GCK mutations with hyperglycemia sufficient to merit treatment. INVESTIGATION: In both women, DNA from chorionic villus sampling, performed after high-risk aneuploidy screening, showed the fetus had inherited the GCK mutation. Therefore, maternal hyperglycemia was not treated. Both offspring had a normal birth weight and no peripartum complications. CONCLUSIONS: In pregnancies where the mother has hyperglycemia due to a GCK mutation, knowing the fetal GCK genotype guides the management of maternal hyperglycemia. Fetal genotyping should be performed when fetal DNA is available from invasive prenatal diagnostic testing. PMID- 22773698 TI - Validation of previous computer models and MD simulations of discoidal HDL by a recent crystal structure of apoA-I. AB - HDL is a population of apoA-I-containing particles inversely correlated with heart disease. Because HDL is a soft form of matter deformable by thermal fluctuations, structure determination has been difficult. Here, we compare the recently published crystal structure of lipid-free (Delta185-243)apoA-I with apoA I structure from models and molecular dynamics (MD) simulations of discoidal HDL. These analyses validate four of our previous structural findings for apoA-I: i) a baseline double belt diameter of 105 A ii) central alpha helixes with an 11/3 pitch; iii) a "presentation tunnel" gap between pairwise helix 5 repeats hypothesized to move acyl chains and unesterified cholesterol from the lipid bilayer to the active sites of LCAT; and iv) interchain salt bridges hypothesized to stabilize the LL5/5 chain registry. These analyses are also consistent with our finding that multiple salt bridge-forming residues in the N-terminus of apoA I render that conserved domain "sticky." Additionally, our crystal MD comparisons led to two new hypotheses: i) the interchain leucine-zippers previously reported between the pair-wise helix 5 repeats drive lipid-free apoA-I registration; ii) lipidation induces rotations of helix 5 to allow formation of interchain salt bridges, creating the LCAT presentation tunnel and "zip-locking" apoA-I into its full LL5/5 registration. PMID- 22773700 TI - Diastolic function is reduced in adolescents with type 1 diabetes in response to exercise. AB - OBJECTIVE: To determine whether adolescents with type 1 diabetes have left ventricular functional changes at rest and during acute exercise and whether these changes are affected by metabolic control and diabetes duration. RESEARCH DESIGN AND METHODS: The study evaluated 53 adolescents with type 1 diabetes and 22 control adolescents. Baseline data included peak exercise capacity and body composition by dual-energy X-ray absorptiometry. Left ventricular functional parameters were obtained at rest and during acute exercise using magnetic resonance imaging. RESULTS: Compared with nondiabetic control subjects, adolescents with type 1 diabetes had lower exercise capacity (44.7 +/- 09 vs. 48.5 +/- 1.4 mL/kg fat-free mass [FFM]/min; P < 0.05). Stroke volume was reduced in the diabetes group at rest (1.86 +/- 0.04 vs. 2.05 +/- 0.07 mL/kg FFM; P = 0.02) and during acute exercise (1.89 +/- 0.04 vs. 2.17 +/- 0.06 mL/kg FFM; P = 0.01). Diabetic adolescents also had reduced end-diastolic volume at rest (2.94 +/- 0.06 vs. 3.26 +/- 0.09 mL/kg FFM; P = 0.01) and during acute exercise (2.78 +/- 0.05 vs. 3.09 +/- 0.08 mL/kg FFM; P = 0.01). End-systolic volume was lower in the diabetic group at rest (1.08 +/- 0.03 vs. 1.21 +/- 0.04 mL/kg FFM; P = 0.01) but not during acute exercise. Exercise capacity and resting and exercise stroke volumes were correlated with glycemic control but not with diabetes duration. CONCLUSIONS: Adolescents with type 1 diabetes have reduced exercise capacity and display alterations in cardiac function compared with nondiabetic control subjects, associated with reduced stroke volume during exercise. PMID- 22773701 TI - Circulating osteocalcin level is not associated with incident type 2 diabetes in middle-aged male subjects: mean 8.4-year retrospective follow-up study. AB - OBJECTIVE: Recent human studies suggested that serum osteocalcin is associated with the cross-talk between bone and energy metabolism. The aim of this study was to determine whether serum osteocalcin level is independently associated with the development of type 2 diabetes. RESEARCH DESIGN AND METHODS: A retrospective cohort study was performed of 1,229 nondiabetic men, aged 25-60 years, who were recruited from the Health Promotion Center, Samsung Medical Center, between January 1997 and December 1997. They were followed regularly at the center on an out-patient basis and during hospitalization for a mean of 8.4 years, and the development of type 2 diabetes was determined. RESULTS: In the baseline analysis, BMI, body fat percentage, triglyceride, homeostasis model assessment of insulin resistance value, and plasminogen activator inhibitor-1 levels varied inversely with the osteocalcin tertiles, and serum high-density lipoprotein cholesterol levels increased with the osteocalcin tertiles. However, no differences were observed in fasting glucose and glycated hemoglobin levels across the osteocalcin tertiles. Incident type 2 diabetes occurred in 90 (7.3%) of the study subjects. In Cox proportional hazards models, however, no statistical differences in the development of type 2 diabetes across the osteocalcin tertiles were evident after adjustment of other risk factors for incident diabetes. CONCLUSIONS: Despite baseline associations with favorable metabolic parameters, the serum osteocalcin level was not associated with the development of type 2 diabetes in middle-aged males. PMID- 22773702 TI - Curcumin extract for prevention of type 2 diabetes. AB - OBJECTIVE: To assess the efficacy of curcumin in delaying development of type 2 diabetes mellitus (T2DM) in the prediabetic population. RESEARCH DESIGN AND METHODS: This randomized, double-blinded, placebo- controlled trial included subjects (n = 240) with criteria of prediabetes. All subjects were randomly assigned to receive either curcumin or placebo capsules for 9 months. To assess the T2DM progression after curcumin treatments and to determine the number of subjects progressing to T2DM, changes in beta-cell functions (homeostasis model assessment [HOMA]-beta, C-peptide, and proinsulin/insulin), insulin resistance (HOMA-IR), anti-inflammatory cytokine (adiponectin), and other parameters were monitored at the baseline and at 3-, 6-, and 9-month visits during the course of intervention. RESULTS: After 9 months of treatment, 16.4% of subjects in the placebo group were diagnosed with T2DM, whereas none were diagnosed with T2DM in the curcumin-treated group. In addition, the curcumin-treated group showed a better overall function of beta-cells, with higher HOMA-beta (61.58 vs. 48.72; P < 0.01) and lower C-peptide (1.7 vs. 2.17; P < 0.05). The curcumin-treated group showed a lower level of HOMA-IR (3.22 vs. 4.04; P < 0.001) and higher adiponectin (22.46 vs. 18.45; P < 0.05) when compared with the placebo group. CONCLUSIONS: A 9-month curcumin intervention in a prediabetic population significantly lowered the number of prediabetic individuals who eventually developed T2DM. In addition, the curcumin treatment appeared to improve overall function of beta-cells, with very minor adverse effects. Therefore, this study demonstrated that the curcumin intervention in a prediabetic population may be beneficial. PMID- 22773703 TI - Adiponectin and all-cause mortality in elderly people with type 2 diabetes. AB - OBJECTIVE: To assess the association between serum adiponectin level and all cause mortality in people with type 2 diabetes. Because of the insulin sensitizing, anti-inflammatory, and antiatherogenic effects of adiponectin, we hypothesized that higher adiponectin level would be associated with lower all cause mortality. RESEARCH DESIGN AND METHODS: A total of 609 men and women aged 72 +/- 6.3 years with type 2 diabetes and information on total and high molecular weight adiponectin were followed for a median of 5 years. The longitudinal association between adiponectin and all-cause mortality was analyzed with Cox proportional hazards models with time from adiponectin measurement to death as the time-to-event variable. Analyses were adjusted for demographic variables and significant diabetes parameters, significant cardiovascular parameters, and significant diabetes medications. RESULTS: Total and high molecular weight adiponectin were highly correlated. The highest adiponectin quartile was strongly associated with higher all-cause mortality compared with the lowest quartile (hazard ratio = 4.0 [95% CI: 1.7-9.2]) in the fully adjusted model. These results did not change in analyses stratified by sex and thiazolidinedione use, after exclusion of people who died within one year of adiponectin measurement, or when change in weight before adiponectin measurement was considered. CONCLUSIONS: Contrary to our hypothesis, higher adiponectin level was related to higher all cause mortality. This association was not explained by confounding by other characteristics, including medications or preceding weight loss. PMID- 22773705 TI - Fasting glucose, obesity, and coronary artery calcification in community-based people without diabetes. AB - OBJECTIVE: Our objective was to assess whether impaired fasting glucose (IFG) and obesity are independently related to coronary artery calcification (CAC) in a community-based population. RESEARCH DESIGN AND METHODS: We assessed CAC using multidetector computed tomography in 3,054 Framingham Heart Study participants (mean [SD] age was 50 [10] years, 49% were women, 29% had IFG, and 25% were obese) free from known vascular disease or diabetes. We tested the hypothesis that IFG (5.6-6.9 mmol/L) and obesity (BMI >=30 kg/m(2)) were independently associated with high CAC (>90th percentile for age and sex) after adjusting for hypertension, lipids, smoking, and medication. RESULTS: High CAC was significantly related to IFG in an age- and sex-adjusted model (odds ratio 1.4 [95% CI 1.1-1.7], P = 0.002; referent: normal fasting glucose) and after further adjustment for obesity (1.3 [1.0-1.6], P = 0.045). However, IFG was not associated with high CAC in multivariable-adjusted models before (1.2 [0.9-1.4], P = 0.20) or after adjustment for obesity. Obesity was associated with high CAC in age- and sex-adjusted models (1.6 [1.3-2.0], P < 0.001) and in multivariable models that included IFG (1.4 [1.1-1.7], P = 0.005). Multivariable-adjusted spline regression models suggested nonlinear relationships linking high CAC with BMI (J-shaped), waist circumference (J-shaped), and fasting glucose. CONCLUSIONS: In this community-based cohort, CAC was associated with obesity, but not IFG, after adjusting for important confounders. With the increasing worldwide prevalence of obesity and nondiabetic hyperglycemia, these data underscore the importance of obesity in the pathogenesis of CAC. PMID- 22773706 TI - Cardiovascular diseases and other evidence for primary care clinical practice. AB - This issue includes several articles about various cardiovascular illnesses.(1-4) and another on a disease with increased risk for heart disease: hereditary hemochromatosis.(5) Yet another explores some myth busting about mortality and diabetes.(6) Two articles provide data with the support of patient and/or family organizations (Parent Heart Watch(1) and the Iron Disorders Institute(5)). Another 2 articles address maternal-child health, one considers treatment of hyperbilirubinemia,(7) and one describes an innovative team structure for pre-, post-, and intrapartum care.(8) We also provide preliminary data on azithromycin for chronic obstructive pulmonary disease. Pop quiz: What is the common contaminant with cocaine that causes serious side effects? What are these side effects? And another: What nonliver disease should be considered for children with elevated transaminase levels? (See the brief reports for answers.) Two reviews provide up-to-the minute practical facts for vaccinations and treatment resistant hypertension that can be immediately incorporated into clinical practice. We also have an update on physician perspectives after 2 years of electronic medical record use and another with insights about the satisfaction of family physicians who are working in health centers in the first few years out of their residency. PMID- 22773704 TI - Glomerular hyperfiltration and renal disease progression in type 2 diabetes. AB - OBJECTIVE: To describe the prevalence and determinants of hyperfiltration (glomerular filtration rate [GFR] >=120 mL/min/1.73 m(2)), GFR decline, and nephropathy onset or progression in type 2 diabetic patients with normo- or microalbuminuria. RESEARCH DESIGN AND METHODS: We longitudinally studied 600 hypertensive type 2 diabetic patients with albuminuria <200 MUg/min and who were retrieved from two randomized trials testing the renal effect of trandolapril and delapril. Target blood pressure (BP) was <120/80 mmHg, and HbA(1c) was <7%. GFR, albuminuria, and glucose disposal rate (GDR) were centrally measured by iohexol plasma clearance, nephelometry in three consecutive overnight urine collections, and hyperinsulinemic euglycemic clamp, respectively. RESULTS: Over a median (range) follow-up of 4.0 (1.7-8.1) years, GFR declined by 3.37 (5.71-1.31) mL/min/1.73 m(2) per year. GFR change was bimodal over time: a larger reduction at 6 months significantly predicted slower subsequent decline (coefficient: 0.0054; SE: 0.0009), particularly among hyperfiltering patients. A total of 90 subjects (15%) were hyperfiltering at inclusion, and 11 of 47 (23.4%) patients with persistent hyperfiltration progressed to micro- or macroalbuminuria versus 53 (10.6%) of the 502 who had their hyperfiltration ameliorated at 6 months or were nonhyperfiltering since inclusion (hazard ratio 2.16 [95% CI 1.13-4.14]). Amelioration of hyperfiltration was independent of baseline characteristics or ACE inhibition. It was significantly associated with improved BP and metabolic control, amelioration of GDR, and slower long-term GFR decline on follow-up. CONCLUSIONS: Despite intensified treatment, patients with type 2 diabetes have a fast GFR decline. Hyperfiltration affects a subgroup of patients and may contribute to renal function loss and nephropathy onset or progression. Whether amelioration of hyperfiltration is renoprotective is worth investigating. PMID- 22773707 TI - The percentage of family physicians attending to women's gender-specific health needs is declining. AB - As the largest and most widely distributed of primary care physicians, family physicians have an important role in providing women's health care, especially in rural and underserved areas. The proportion of family physicians who are attending to women is declining. Policy intervention may be needed to help family physicians maintain the comprehensiveness of care necessary to address the wide range of medical problems of women they encounter within their practices. PMID- 22773708 TI - Warning symptoms and family history in children and young adults with sudden cardiac arrest. AB - BACKGROUND: Children and young adults with undiagnosed cardiovascular disorders at risk for sudden death may have warning symptoms or significant family history that is detectable through screening. The objective of this study was to determine the prevalence of warning symptoms and family history in a cohort of children and young adults who suffered sudden cardiac arrest (SCA). METHODS: A retrospective survey investigating warning symptoms and family history of cardiovascular disease was completed by families with a child or young adult who suffered SCA. RESULTS: Eighty-seven of 146 families (60%) returned a completed survey. The SCA victims were an average age of 16 years (range, <5-29 years), 69% male, and 68% white. Seventy-two percent of SCA victims were reported by their parents to have at least one cardiovascular symptom before SCA, with fatigue (44%) and near-syncope/lightheadedness (30%) the two most common. Twenty-four percent of SCA victims had one or more (average 2.6; range, 1 to 10) events of syncope or unexplained seizure that remained undiagnosed as a cardiac disorder before SCA. Parents reported that cardiovascular symptoms first occurred, on average, 30 months (range, 19 to 71 months) before SCA; a symptom was brought to the attention of the child's physician in 41% of cases. Twenty-seven percent of families reported a family member had suffered sudden death before age 50 because of a heart condition. CONCLUSIONS: Many children and young adults who suffered SCA are reported to have cardiac symptoms or a family history of premature cardiac death. Syncope and unexplained seizure activity are distinct events but often go unrecognized as ominous signs of underlying cardiovascular disease. Physician education and increased public awareness regarding cardiovascular warning signs in the young may improve early detection of those at risk and prevent tragedies. PMID- 22773710 TI - Body mass index, diabetes, hypertension, and short-term mortality: a population based observational study, 2000-2006. AB - BACKGROUND: Published studies about the association of obesity with mortality have used body mass index (BMI) data collected more than 10 years ago, potentially limiting their current applicability, particularly given evidence of a secular decline in obesity-related mortality. The objective of this study was to examine the association between BMI and mortality in a representative, contemporary United States sample. METHODS: This was a population-based observational study of data from 50,994 adults aged 18 to 90 years who responded to the 2000 to 2005 Medical Expenditures Panel Surveys. Cox regression analyses were employed to model survival during up to 6 years of follow-up (ascertained via National Death Index linkage) by self-reported BMI category (underweight, <20 kg/m(2); normal weight, 20-<25 [reference]; overweight, 25-<30; obese, 30-<35; severely obese, >=35), without and with adjustment for diabetes and hypertension. Survival by BMI category also was modeled for diabetic and hypertensive individuals. All models were adjusted for sociodemographics, smoking, and Medical Expenditures Panel Surveys response year. RESULTS: In analyses not adjusted for diabetes or hypertension, only severe obesity was associated with mortality (adjusted hazard ratio, 1.26; 95% confidence interval, 1.00-1.59). After adjusting for diabetes and hypertension, severe obesity was no longer associated with mortality, and milder obesity (BMI 30-<35) was associated with decreased mortality (adjusted hazard ratio, 0.81; 95% confidence interval, 0.68-0.97). There was a significant interaction between diabetes (but not hypertension) and BMI (F [4, 235] = 2.71; P = .03), such that the mortality risk of diabetes was lower among mildly and severely obese persons than among those in lower BMI categories. CONCLUSIONS: Obesity-associated mortality risk was lower than estimated in studies employing older BMI data. Only severe obesity (but not milder obesity or overweight) was associated with increased mortality, an association accounted for by coexisting diabetes and hypertension. Mortality in diabetes was lower among obese versus normal weight individuals. PMID- 22773709 TI - Low education as a risk factor for undiagnosed angina. AB - BACKGROUND: Early awareness, recognition, and treatment of angina can help prevent or delay an acute myocardial infarction and potentially delay death. A patient's educational level may affect a physician's diagnosis of angina and/or a patient's symptom recognition. The objective of this study was to determine whether low education is a risk factor for undiagnosed angina. METHODS: This was a cross-sectional observational study based on data from the National Health and Nutrition Examination Survey 2001 to 2008, providing a nationally representative sample of adults >=40 years of age with angina based on physician diagnosis, presence of angina symptoms based on the Rose Questionnaire, or both. Educational attainment (high school or less vs more than high school) was the independent variable of interest. Undiagnosed angina (angina symptoms in the absence of angina diagnosis) was the dependent variable. We used logistic regression to control for age, sex, race/ethnicity, income, and health care visit during the past year. RESULTS: Low education was associated with undiagnosed angina (odds ratio: 1.43; 95% confidence interval: 1.01-2.03). Other undiagnosed angina predictors included being female, being black, and having no health care visit during the past year. CONCLUSIONS: Low education is associated with undiagnosed angina. These results underscore the need for providers to ask about angina symptoms and confirm patients' understanding of their angina diagnosis among those with low education. PMID- 22773711 TI - A national survey of hemochromatosis patients. AB - BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease in the United States, but little is known about the diagnosis from the patient's perspective. The purpose of this study was to characterize the circumstances surrounding the diagnosis of HH and assess treatments and health information needs. METHODS: We surveyed US adults aged 18 years and older who were diagnosed with HH after 1996. Response rate was 46%, with a total sample size of 979. Respondents were asked about the use of genetic and clinical markers in their diagnosis, current treatments, and health information needs. RESULTS: Results were stratified by age, education, and income status. Total of 90.0% of women and 75.5% of men were genetically tested for HH (P < .01). Approximately half (52.5%) were diagnosed by a gastroenterologist, hematologist, or other specialty physician and half were diagnosed by a primary care provider. Most of the respondents thought their HH had improved with the initial treatment and most patients were still receiving treatment for HH. Patient interest in learning more about specific hemochromatosis topics was generally high. CONCLUSIONS: Since the introduction of genetic identification of HH, these tests have been used in the diagnosis of the majority of patients. Primary care physicians may need to be more aware HH and strategies for diagnosis. PMID- 22773712 TI - Clinician adherence to guideline for phototherapy use in newborns. AB - OBJECTIVES: The objectives of this study were (1) to determine clinician adherence to the 2004 American Academy of Pediatrics guideline for phototherapy use in newborns; (2) to compare adherence to the guideline in 2 different hospitals; and (3) to determine whether adherence to the guideline improved after the phototherapy nomogram was available in newborn charts. METHODS: This study was a retrospective review of medical records of 1160 newborns receiving care at the normal newborn nurseries at 2 Twin City, MN, hospitals. Four hundred thirty six infants received phototherapy. RESULTS: When phototherapy was administered, it was indicated in 37% of cases and not indicated in 8%. In 56% of cases it was considered subthreshold. When phototherapy was not administered, it was appropriate in 99% of cases but was inappropriate or missed in 1% of cases. There was a significant difference in clinician adherence to the phototherapy guidelines between the hospitals. The addition of the phototherapy nomogram to the newborn charts did not change adherence to the guideline. CONCLUSIONS: Clinicians infrequently missed providing phototherapy when it was indicated. Most infants received phototherapy when their bilirubin level was in the "optional" range. The interhospital variability of guideline adherence confirms results found in other studies. Because the addition of the phototherapy nomogram alone did not improve adherence to the guideline, alternative interventions targeted at nurseries should be considered. PMID- 22773713 TI - Azithromycin for bronchial asthma in adults: an effectiveness trial. AB - BACKGROUND: Macrolides have antimicrobial and anti-inflammatory properties that may be useful in the treatment of chronic asthma. METHODS: We performed a randomized, placebo-controlled, double-blinded effectiveness trial of 12 weekly doses of adjunctive azithromycin, with follow-up to 1 year after randomization, in adults with persistent asthma. Measurements included overall asthma symptoms, asthma quality of life (AQL), and asthma control. Eligible subjects who declined to participate in randomization were offered enrollment into a parallel open label (OL) azithromycin treatment arm. RESULTS: Of 304 adult asthma patients screened, 97 (32%) were enrolled: 38 were randomized to azithromycin, 37 were randomized to placebo, and 22 opted in as OL subjects. OL subjects had higher rates of severe persistent asthma compared with randomized subjects (32% vs 8%, respectively; P = .012). At 1 year, compared with the placebo arm, subjects randomized to azithromycin were more likely to have an AQL score >=1 unit increase compared with baseline, but this difference was not statistically significant (36% vs 21% for placebo; P = .335). Compared with placebo, OL subjects had significant improvements in overall asthma symptoms from baseline (P = .0196), AQL (P = .0006), and asthma control (P = .0148). CONCLUSIONS: Adults with asthma who were randomized to azithromycin did not show statistically significant improvement in asthma outcomes, although the study was underpowered to detect clinical improvement in 15% (number needed to treat = 7). Adults with severe persistent asthma who elected OL treatment documented clinical improvements in asthma symptoms, AQL, and asthma control that persisted after completion of OL azithromycin (number needed to treat = 2). PMID- 22773715 TI - Satisfaction of family physicians working in community health centers. AB - BACKGROUND: Community health centers (CHCs) receive $2.9 billion in federal funding to provide primary care to 20 million people annually, and these numbers are increasing. Understanding of physician satisfaction in CHCs may help guide recruitment and retention efforts aimed at expanding CHC programs. The objective of this study was to contrast the satisfaction of family physicians working in CHCs with the satisfaction of family physicians working in other practice settings. METHODS: Analysis of 4 cross-sectional surveys of recent residency graduates from the Washington, Wyoming, Alaska, Montana, and Idaho Family Medicine Residency Network. Surveys were conducted approximately every 3 years from 2000 to 2010. Main outcome measures included self-reported satisfaction with residency training, practice, and specialty on a 1 (low) to 5 (high) scale. RESULTS: Eight hundred ninety-three family physician responded (response rate, 61%), of whom 129 were CHC physicians and 764 were non-CHC physicians. Compared with non-CHC physicians, higher proportions of CHC physicians reported being highly satisfied with their residency training (79% vs 61%; P < .01) and choice of specialty (74% vs 60%; P < .01). In contrast, lower proportions of CHC physicians were highly satisfied with their employers (62% vs 72%; P = .05). [corrected]. There were no differences in satisfaction with practice partners, income, practice location, or work hours. After adjustment for physician, practice, and community characteristics, CHC physicians were more likely to be highly satisfied with their residency training (odds ratio, 2.6; P = .001) and their choice of specialty (odds ratio, 1.7; P = .03). CHC physicians were less likely to be highly satisfied with their employers (odds ratio, 0.5; P < .01). CONCLUSIONS: The lower level of satisfaction reported by CHC physicians has implications for workforce recruitment and retention in CHC settings. In an era of CHC growth, efforts to improve physician relationships with employers may be a potential target for enhancing the physician workforce in CHCs. PMID- 22773714 TI - Cancer screening of long-term cancer survivors. AB - BACKGROUND: Although 64% of cancer survivors are expected to live at least 5 years beyond diagnosis, the receipt of cancer screening by this population is unclear. The objective of this study was to assess the relation between a cancer diagnosis and future cancer screening, exploring provider-, patient-, and cancer specific factors that explain observed relationships. METHODS: The Wisconsin Longitudinal Study (WLS) and Wisconsin Tumor Registry were used to identify 2 participant groups: 415 patients diagnosed with nonmetastatic cancer between 1992 to 1993 (before cancer) and 2003 to 2004 (after cancer) and 4680 controls (no cancer). Adjusted average predicted probabilities of cancer screening were estimated with models that first did not include and then included, provider (provider relationship length), participant (depressive symptoms per the Center for Epidemiologic Studies Depression Scale), and cancer-specific (time since diagnosis) factors. Participants with a history of cancer associated with a given screening test were then excluded to assess whether relationships are explained by screening for recurrence versus second cancers. RESULTS: Female cancer survivors were more likely than no-cancer controls to undergo pelvic/Papanicolaou screening (survivors: 70%, 95% confidence interval [CI]: 63% to 76%; controls: 61%, 95% CI: 59% to 63%) and mammography screening (survivors: 86%, 95% CI: 78% to 90%; controls: 76%, 95% CI: 74% to 77%), though male cancer survivors were not more likely to receive prostate exams (survivors: 76%, 95% CI: 70% to 82%; controls: 69%, 95% CI: 67% to 71%). After excluding people with a history of the cancer being screened for, there were few significant differences in cancer screening between short- or long-term survivors (>=5 years) and no-cancer controls. Relationships were not sensitive to adjustment for provider or participant factors. CONCLUSIONS: The significant positive differences in cancer screening between people with and without cancer can be explained by screening for recurrence. Long-term cancer survivors are not more likely to receive follow up screening for second cancers. This information should be used by providers to ensure patients receive recommended follow-up preventive care. PMID- 22773717 TI - Resistant hypertension. AB - Resistant hypertension (RH) is defined as blood pressure above a goal despite adherence to at least 3 optimally dosed antihypertensive medications of different classes, one of which is a diuretic. Evaluation of possible RH begins with an assessment of adherence to medications. The white-coat effect should be ruled out by out-of-office blood pressure monitoring. Obesity, heavy alcohol intake, and interfering substances all contribute to RH. Dietary sodium restriction is an important part of management. RH may be secondary to problems such as renal disease, obstructive sleep apnea, or aldosteronism, and testing for these conditions should be considered. Adequate diuretic treatment is a key part of therapy. Chlorthalidone is more effective than hydrochlorothiazide in reducing blood pressure because it is more potent and lasts longer. In addition, it may reduce cardiovascular events to a greater extent than hydrochlorothiazide. When glomerular filtration rate is <30 mL/min, a loop diuretic usually is needed. The addition of spironolactone, with careful attention to potassium levels, is an evidence-based strategy for the treatment of RH. Other strategies include use of a vasodilating beta-blocker, adding a long-acting nondihydropyridine calcium channel blocker, or adding clonidine. When blood pressure is not coming under control despite 4 or 5 agents, referral to a hypertension specialist may be warranted. PMID- 22773716 TI - A culture of care: the French approach to cardiovascular risk factor management. AB - OBJECTIVE: The objective of this study was to describe French primary care physicians' beliefs about cardiovascular disease (CVD) risk factors and best practices for managing CVD. METHODS: This study comprised a purposive convenience sample of 656 primary care physicians in France, recruited from contacts made through the French Society of General Medicine. We compiled the physicians' responses to free text questions taken from an Internet-based survey and analyzed them using a qualitative approach. Physician's responses were inductively analyzed using content analysis. Responses were thematically coded, tabulated, and computed for frequencies. Overall themes and verbatim examples are presented in this article. RESULTS: The French physicians in our study are generally happy with their country's health care system and cite equity as the primary reason. Interestingly, along with food and lifestyle differences, they also cite equity of their health system as the reason for the lower CVD death rate in France, Japan, and Israel compared with the United States. The physicians believe that they are successful at managing CVD risk factors by emphasizing aspects of the doctor-patient relationship, including spending more time with patients and focusing on education. CONCLUSIONS: Physicians who are on the front line of care and management offer a fresh perspective on best practices for CVD prevention and management. The equity of the French health care system supports a "culture of care" in France that might lead to better outcomes for CVD risk factor patients than in the United States. PMID- 22773718 TI - Update on adult immunizations. AB - The past few years have seen numerous additions and modifications to the current immunization schedules. Starting with the 2010 to 2011 influenza season, the Centers for Disease Control and Prevention have recommended universal annual influenza vaccination for all persons without a contraindication who are 6 months of age and older, including healthy persons aged 19 to 49 years. Hepatitis B vaccination is now recommended for all susceptible diabetics <=60 years of age. One dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine, adsorbed, is recommended to replace one tetanus and diphtheria toxoids adsorbed (adult) vaccination for all adults, including those 65 years of age or older, who are anticipating contact with infants and unvaccinated pregnant women (preferably during the second or third trimester). All adult vaccines remain underused. This article will summarize the most recent changes in the adult immunization recommendations of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention. PMID- 22773719 TI - How we built our team: collaborating with partners to strengthen skills in pregnancy, delivery, and newborn care. AB - We describe how collaboration with outpatient community health centers and other disciplines resulted in the creation of a novel interdisciplinary inpatient maternal child health system that focuses on safety and collaboration. Our maternal child health faculty team includes a mix of fellowship- and non fellowship-trained, inpatient- and outpatient-based family physicians. Our team provides a sustainable framework for faculty to practice both inpatient and outpatient maternity care and provides strong role models for our trainees. PMID- 22773720 TI - Perspectives on electronic medical record implementation after two years of use in primary health care practice. AB - PURPOSE: This qualitative study explored the experiences of primary health care providers and staff who had moved beyond the stage of implementing electronic medical records (EMRs) in their practices to using this technology on an on-going basis. METHODS: A descriptive qualitative approach was used. Semistructured interviews were conducted with 19 participants. Data analysis was iterative and interpretive. RESULTS: Factors that hindered and motivated ongoing EMR use emerged. Factors that hindered use included (1) information technology challenges such as learning to use the EMR and the computer, electronic connectivity, and scanning; and (2) variability in on-going EMR use. Two factors motivated ongoing use: (1) improved efficiency in patient care, and (2) confidence with computers and EMR software. CONCLUSIONS: Different issues in the use of EMRs surface as primary health care providers and staff mature in their use of this technology. Ongoing use of the EMR may be facilitated by confidence with the technology as well as providers' perceptions of efficiency in patient care. Optimal use of the EMR could be facilitated through assessing and enhancing computer skills, working toward consistent data entry and use of the EMR, and developing strategies to address issues such as scanning and electronic connectivity. PMID- 22773721 TI - Agranulocytosis from levamisole-adulterated cocaine. AB - INTRODUCTION: Afebrile neutropenia with an absolute neutrophil count (ANC) of zero in a nonimmunocompromised individual is unusual. Outlined is a case of agranulocytosis likely due to levamisole laced cocaine. Given recent publications in the news media and medical journals, this is a pertinent issue for primary care providers. CASE: A 57-year-old female presented with painful bowel movements and difficulty eating. Physical examination revealed two exquisitely tender ulcerated lesions on her lower lip and anus. Laboratory data revealed an ANC of 0 and urine drug screen positive for cocaine. She was prophylaxed with acyclovir, diflucan, and ciprofloxacin, and was started on granulocyte colony stimulating factor for four days. Her ANC normalized, but the cause of her severe neutropenia remained unclear. DISCUSSION: Levamisole is a veterinary antihelminthic used for treatment of rheumatoid arthritis and colorectal cancer in humans. 88% of regional cocaine samples are testing positive for levamisole, which is thought to potentiate cocaine's effects but can also cause agranulocytosis. CONCLUSIONS: Our patient did not fit the clinical picture for malignancy, viral infection, or bone marrow pathology. Given the high rate of levamisole adulterated cocaine and an otherwise negative work-up, this is the most likely explanation for her agranulocytosis. PMID- 22773722 TI - Levamisole-adulterated cocaine: a case series. AB - The percentage of cocaine adulterated with levamisole is steadily increasing in the United States. In susceptible persons, this combination of drugs leads to a clinical syndrome that can include leukopenia and cutaneous manifestations. Many patients also demonstrate positive autoimmune markers. Biopsies of skin lesions often reveal a thrombotic pattern, leukocytoclastic vasculitis, or both. We report 2 cases of this clinical phenomenon, one of which was severe enough to require skin grafting. It is important for clinicians be aware of this emerging public health threat. PMID- 22773723 TI - Consider muscle disease in children with elevated transaminase. AB - The transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are markers of hepatocellular injury but are highly concentrated in muscle cells. Consequently, muscular dystrophies such as Duchenne muscular dystrophy, lead to hypertransaminasemia. Elevation in ALT and AST is most striking during the early stages of disease, before onset of or when only subtle signs of muscle disease are present. Thus, the incidental finding of elevated ALT/AST may be the presenting sign of muscle disease in many children and provides an opportunity for early diagnosis. Many physicians, however, pursue extensive workup for liver disease in children who present with the incidental finding of elevated ALT/AST. This results in delayed diagnosis and initiation of treatment and increased expense and may lead to unnecessary invasive procedures. We report 12 patients with muscle disease who presented with a variety of symptoms and were found to have an incidental finding of elevated ALT/AST. We propose a rapid screening process for evaluating children with the incidental finding of elevated ALT/AST to shorten the time to diagnosis of muscle disease. PMID- 22773724 TI - Anomalous coronary artery found in the syncopal workup of an elderly man. AB - Syncope, defined as a transient loss of consciousness, is seen in 1% of all visits to emergency departments and urgent care clinics in the United States. Syncope is categorized as cardiogenic, neurologic, or psychogenic. Anomalies of the coronary arteries are rare, and anomalous coronary arteries present as syncope more often in the young than in the elderly; syncope rarely occurs in patients 65 years of age and older. There are 2 major variants of coronary anomalies. In the first variant, the left main coronary artery arises from the right aortic sinus. In the second variant, the right coronary artery arises from the left aortic sinus. The risk of sudden death is higher in patients with the left coronary artery arising from the right aortic sinus. We present a case of an anomalous coronary artery discovered during the syncopal workup in a 66-year-old man because no such cases have been published in the United States. We will discuss the management of anomalous coronary arteries as well as a systematic approach to the diagnosis and management of syncope. PMID- 22773725 TI - Quiet healing. AB - Both physicians and patients want deeply healing doctor-patient relationships. Too often, though, the ever-expanding demands of medical practice combine with the defenses of the patient to create doctor-patient isolation. Eastern and Western cosmologies and traditions may encourage different approaches to human interaction and healing. At times, probing the patient with more questions may open up a story vital to transformative healing. However, this narrative essay uses a personal experience as a patient of a Japanese traditional healer and Zen practitioner to explore the value of a quiet approach to patient care. PMID- 22773726 TI - American Board of Family Medicine heart failure self-assessment module simulation actions vis-a-vis guideline recommendations. PMID- 22773727 TI - Does patient assessment of the quality of the primary care they receive predict subsequent outcomes?: An Oklahoma Physicians Resource/Research Network (OKPRN) study. AB - BACKGROUND: We analyzed data from a cohort of 782 older patients assembled in 1999 to 2000 to determine whether their baseline assessments of the quality of their primary care measured using the Components of Primary Care Index (CPCI) were associated with subsequent changes in health-related quality of life and/or survival. METHODS: Longitudinal growth curve models were used to analyze changes in Quality of Well-Being scores over an average of 2.07 years. Cox proportional hazards models were used to identify variables associated with mortality over an average of 8.91 years (6,966 person-years). To reduce confounding by severity of illness, subjects were stratified into 3 groups based on disability and use rates. Within subgroups, we controlled for number of chronic illnesses and scores on the General Health subscale of the Medical Outcomes Study Short Form-36. We also controlled for baseline age, gender, marital status, income, body mass index, educational attainment, duration of the relationship with current primary care physician, and number of visits to the primary care physician in the year before enrollment. Analyses took into account clustering of patients within primary care physician. RESULTS: Neither total CPCI nor any CPCI subscale score was associated with Quality of Well-Being Self-administered Scale change over time or survival. CONCLUSIONS: Assuming that effective primary care results in better health-related quality of life and longer survival and that the CPCI captures important primary care attributes, older patients' level of satisfaction with the quality of their primary care may not be a good surrogate measure of effectiveness. PMID- 22773728 TI - Polyclonal CD4+Foxp3+ Treg cells induce TGFbeta-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome. AB - Interplay between Foxp3(+) regulatory T cells (Treg) and dendritic cells (DCs) maintains immunologic tolerance, but the effects of each cell on the other are not well understood. We report that polyclonal CD4(+)Foxp3(+) Treg cells induced ex vivo with transforming growth factor beta (TGFbeta) (iTreg) suppress a lupus like chronic graft-versus-host disease by preventing the expansion of immunogenic DCs and inducing protective DCs that generate additional recipient CD4(+)Foxp3(+) cells. The protective effects of the transferred iTreg cells required both interleukin (IL)-10 and TGFbeta, but the tolerogenic effects of the iTreg on DCs, and the immunosuppressive effects of these DCs were exclusively TGFbeta dependent. The iTreg were unable to tolerize Tgfbr2-deficient DCs. These results support the essential role of DCs in 'infectious tolerance' and emphasize the central role of TGFbeta in protective iTreg/DC interactions in vivo. PMID- 22773730 TI - Can social interventions prevent tuberculosis?: the Papworth experiment (1918 1943) revisited. AB - RATIONALE: There is consensus on the need to address social determinants of tuberculosis (TB) to achieve TB control, but evidence based on interventions is lacking. OBJECTIVES: We reanalyzed data from the sociomedical experiment performed at the Papworth Village Settlement in England, where the impact of stable employment and adequate housing and nutrition on the incidence of TB infection and disease in children living with parents with active TB was documented during 1918-1943. METHODS: Information on 315 children of patients, who lived at Papworth, was abstracted from a published monograph. Overall and age specific occurrence of TB infection, disease, and deaths among children born in the settlement (village-born cohort) were compared with those of children born outside and admitted later (admitted cohort) to Papworth. MEASUREMENTS AND MAIN RESULTS: The annual risks of infection in the village-born and admitted cohorts were 20 and 24%, respectively. Of 24 children who developed TB disease, only one was village-born. Among children 5 years of age or less, there was zero incidence of TB in the village-born, compared with five cases (1,217/100,000 person-years) among children born outside Papworth. In the admitted cohort, among children 13 years of age and older, the incidence of TB before admission to Papworth was 5,263/100,000 person-years, whereas it was 341/100,000 person-years while living in Papworth. CONCLUSIONS: At Papworth social interventions including adequate nutrition did not reduce TB transmission but did reduce the incidence of TB disease in children living with parents with active TB. These results are relevant today for prevention of TB in children of patients with active TB, particularly with multidrug-resistant TB in high-burden settings. PMID- 22773729 TI - Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype. AB - RATIONALE: Obesity is associated with increased prevalence and severity of asthma. Adipose tissue macrophages can contribute to the systemic proinflammatory state associated with obesity. However, it remains unknown whether alveolar macrophages have a unique phenotype in overweight/obese patients with asthma. OBJECTIVES: We hypothesized that leptin levels would be increased in the bronchoalveolar lavage fluid from overweight/obese subjects and, furthermore, that leptin would alter the response of alveolar macrophages to bacterial LPS. METHODS: Forty-two subjects with asthma and 46 healthy control subjects underwent research bronchoscopy. Bronchoalveolar lavage fluid from 66 was analyzed for the level of cellular inflammation, cytokines, and soluble leptin. Cultured primary macrophages from 22 subjects were exposed to LPS, leptin, or leptin plus LPS. Cytokines were measured in the supernatants. MEASUREMENTS AND MAIN RESULTS: Leptin levels were increased in overweight/obese subjects, regardless of asthma status (P = 0.013), but were significantly higher in overweight/obese subjects with asthma. Observed levels of tumor necrosis factor-alpha were highest in overweight/obese subjects with asthma. Ex vivo studies of primary alveolar macrophages indicated that the response to LPS was most robust in alveolar macrophages from overweight/obese subjects with asthma and that preexposure to high-dose leptin enhanced the proinflammatory response. Leptin alone was sufficient to induce production of proinflammatory cytokines from macrophages derived from overweight/obese subjects with asthma. CONCLUSIONS: Ex vivo studies indicate that alveolar macrophages derived from overweight/obese subjects with asthma are uniquely sensitive to leptin. This macrophage phenotype, in the context of higher levels of soluble leptin, may contribute to the pathogenesis of airway disease associated with obesity. PMID- 22773731 TI - Asthmatic granulomatosis: a novel disease with asthmatic and granulomatous features. AB - RATIONALE: Severe asthma represents 5-10% of all asthma, yet remains problematic and poorly understood. Although it is increasingly recognized as consisting of numerous heterogenous phenotypes, their immunopathology, particularly in the distal airways and interstitium, remains poorly described. OBJECTIVES: To identify the pathobiology of atypical difficult asthma. METHODS: We report 10 from a total of 19 patients (17 women and 2 men) meeting asthma and severe asthma definitions, requiring daily systemic corticosteroid (CS) use, with inconsistent abnormalities on chest computed tomography scans, who underwent video-assisted thoracoscopic biopsies for further diagnosis and management. MEASUREMENTS AND MAIN RESULTS: The pathology of 10 of the 19 cases revealed small airway changes consistent with asthma (eosinophilia, goblet cell hyperplasia), but with the unexpected finding of interstitial nonnecrotizing granulomas. These patients had no evidence for hypersensitivity pneumonitis, but 70% of cases had a personal or family history of autoimmune-like disease. The 10 cases were treated with azathioprine, mycophenolic acid, methotrexate, or infliximab. Nine of 10 showed decreased CS requirements and improved or maintained FEV(1) despite lower CS doses. Of the remaining nine patients, six manifested asthmatic small airway disease, alone or in combination with alveolar septal mononuclear cells, but no granulomas, whereas three manifested other pathologic findings (aspiration, pneumonia, or thromboemboli). CONCLUSIONS: These data suggest that a subset of severe "asthma" manifests a granulomatous pathology, which we term "asthmatic granulomatosis." Although identification of this disease currently requires a thorascopic biopsy, alternative approaches to therapy lead to improvement in outcomes. PMID- 22773732 TI - Spatial clusters of nontuberculous mycobacterial lung disease in the United States. AB - RATIONALE: Prevalence of pulmonary nontuberculous mycobacterial (PNTM) disease varies by geographic region, yet the factors driving these differences remain largely unknown. OBJECTIVES: To identify spatial clusters of PNTM disease at the county level and to describe environmental and sociodemographic factors predictive of disease. METHODS: PNTM cases identified from a nationally representative sample of Medicare Part B beneficiaries from 1997 to 2007 were geocoded by county and state of residence. County-level PNTM case counts and Medicare population data were then uploaded into SaTScan to identify significant spatial clusters and low-risk areas of disease. High-risk and low-risk counties were then compared to identify significant sociodemographic and environmental differences. MEASUREMENTS AND MAIN RESULTS: We identified seven significant (P < 0.05) clusters of PNTM cases. These high-risk areas encompassed 55 counties in 8 states, including parts of California, Florida, Hawaii, Louisiana, New York, Oklahoma, Pennsylvania, and Wisconsin. Five low-risk areas were also identified, which encompassed 746 counties in 23 states, mostly in the Midwest. Counties in high-risk areas were significantly larger, had greater population densities, and higher education and income levels than low-risk counties. High-risk counties also had higher mean daily potential evapotranspiration levels and percentages covered by surface water, and were more likely to have greater copper and sodium levels in the soil, although lower manganese levels. CONCLUSIONS: Specific environmental factors related to soil and water exposure appear to increase the risk of PNTM infection. Still, given that environmental sources of NTM are ubiquitous and PNTM disease is rare, both host susceptibility and environmental factors must be considered in explaining disease development. PMID- 22773733 TI - Functional consequences of PRPF39 on distant genes and cisplatin sensitivity. AB - Variation in gene expression has been found to be important in disease susceptibility and pharmacogenomics. Local and distant expression quantitative trait loci (eQTLs) have been identified via genome-wide association study (GWAS); yet the functional analysis of these variants has been challenging. The aim of this study was to unravel the functional consequence of a gene with a local SNP with evidence for local and distant regulatory roles in cellular sensitivity to cisplatin, one of the most widely used chemotherapeutic drugs. To this end, we measured cellular susceptibility to cisplatin in 176 HapMap lymphoblastoid cell lines derived from Yoruba individuals from Ibadan, Nigeria. The 276 cytotoxicity associated SNPs at the suggestive threshold of P <= 0.0001 were significantly enriched for eQTLs. Of these SNPs, we found one intronic SNP, rs17115814, that had a significant relationship with the expression level of its host gene, PRPF39 (P= 0.0007), and a significant correlation with the expression of over 100 distant transcripts (P <= 0.0001). Successful knockdown of PRPF39 expression using siRNA resulted in a significant increase in cisplatin resistance. We then measured the expression of 61 downstream targets after PRPF39 knockdown and found 53 gene targets had significant (P <= 0.05) expression changes. Included in the list of genes that significantly changed after PRPF39 knockdown were MAP3K4 and TFPD2, two important signaling genes previously shown to be relevant in cisplatin response. Thus, modulation of a local target gene identified through a GWAS was followed by a downstream cascade of gene expression changes resulting in greater resistance to cisplatin. PMID- 22773734 TI - Abnormal p38alpha mitogen-activated protein kinase signaling in dilated cardiomyopathy caused by lamin A/C gene mutation. AB - We previously interrogated the transcriptome in heart tissue from Lmna(H222P/H222P) mice, a mouse model of cardiomyopathy caused by lamin A/C gene (LMNA) mutation, and found that the extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase branches of the mitogen-activated protein (MAP) kinase signaling pathway were abnormally hyperactivated prior to the onset of significant cardiac impairment. We have now used an alternative gene expression analysis tool to reanalyze this transcriptome and identify hyperactivation of a third branch of the MAP kinase cascade, p38alpha signaling. Biochemical analysis of hearts from Lmna(H222P/H222P) mice showed enhanced p38alpha activation prior to and after the onset of heart disease as well as in hearts from human subjects with cardiomyopathy caused by LMNA mutations. Treatment of Lmna(H222P/H222P) mice with the p38alpha inhibitor ARRY-371797 prevented left ventricular dilatation and deterioration of fractional shortening compared with placebo-treated mice but did not block the expression of collagen genes involved in cardiac fibrosis. These results demonstrate that three different branches of the MAP kinase signaling pathway with overlapping consequences are involved in the pathogenesis of cardiomyopathy caused by LMNA mutations. They further suggest that pharmacological inhibition of p38alpha may be useful in the treatment of this disease. PMID- 22773735 TI - An ancient founder mutation in PROKR2 impairs human reproduction. AB - Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutation's age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same ~123 kb haplotype whose population frequency is <=10%. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproduction. PMID- 22773739 TI - Complete nucleotide sequence of the multidrug resistance IncA/C plasmid pR55 from Klebsiella pneumoniae isolated in 1969. AB - OBJECTIVES: To determine the complete nucleotide sequence of the multidrug resistance IncA/C plasmid pR55 from a clinical Klebsiella pneumoniae strain that was isolated from a urinary tract infection in 1969 in a French hospital and compare it with those of contemporary emerging IncA/C plasmids. METHODS: The plasmid was purified and sequenced using a 454 sequencing approach. After draft assembly, additional PCRs and walking reads were performed for gap closure. Sequence comparisons and multiple alignments with other IncA/C plasmids were done using the BLAST algorithm and CLUSTAL W, respectively. RESULTS: Plasmid pR55 (170 810 bp) revealed a shared plasmid backbone (>99% nucleotide identity) with current members of the IncA/C(2) multidrug resistance plasmid family that are widely disseminating antibiotic resistance genes. Nevertheless, two specific multidrug resistance gene arrays probably acquired from other genetic elements were identified inserted at conserved hotspot insertion sites in the IncA/C backbone. A novel transposon named Tn6187 showed an atypical mixed transposon configuration composed of two mercury resistance operons and two transposition modules that are related to Tn21 and Tn1696, respectively, and an In0-type integron. CONCLUSIONS: IncA/C(2) multidrug resistance plasmids have a broad host range and have been implicated in the dissemination of antibiotic resistance among Enterobacteriaceae from humans and animals. This typical IncA/C(2) genetic scaffold appears to carry various multidrug resistance gene arrays and is now also a successful vehicle for spreading AmpC-like cephalosporinase and metallo beta-lactamase genes, such as bla(CMY) and bla(NDM), respectively. PMID- 22773738 TI - Novel fragments of clavulanate observed in the structure of the class A beta lactamase from Bacillus licheniformis BS3. AB - OBJECTIVES: Our aim was to unravel the inactivation pathway of the class A beta lactamase produced by Bacillus licheniformis BS3 (BS3) by clavulanate. METHODS: The interaction between clavulanate and BS3 was studied by X-ray crystallography, pre-steady-state kinetics and mass spectrometry. RESULTS: The analysis of the X ray structure of the complex yielded by the reaction between clavulanate and BS3 indicates that the transient inactivated form, namely the cis-trans enamine complex, is hydrolysed to an ethane-imine ester covalently linked to the active site serine and a pentan-3-one-5-ol acid. It is the first time that this mechanism has been observed in an inactivated beta-lactamase. Furthermore, the ionic interactions made by the carboxylic group of pentan-3-one-5-ol may provide an understanding of the decarboxylation process of the trans-enamine observed in the non-productive complex observed for the interaction between clavulanate and SHV-1 and Mycobacterium tuberculosis beta-lactamase (Mtu). CONCLUSIONS: This work provides a comprehensive clavulanate hydrolysis pathway accounting for the observed acyl-enzyme structures of class A beta-lactamase/clavulanate adducts. PMID- 22773736 TI - Excess variants in AFF2 detected by massively parallel sequencing of males with autism spectrum disorder. AB - Autism spectrum disorder (ASD) is a heterogeneous disorder with substantial heritability, most of which is unexplained. ASD has a population prevalence of one percent and affects four times as many males as females. Patients with fragile X E (FRAXE) intellectual disability, which is caused by a silencing of the X-linked gene AFF2, display a number of ASD-like phenotypes. Duplications and deletions at the AFF2 locus have also been reported in cases with moderate intellectual disability and ASD. We hypothesized that other rare X-linked sequence variants at the AFF2 locus might contribute to ASD. We sequenced the AFF2 genomic region in 202 male ASD probands and found that 2.5% of males sequenced had missense mutations at highly conserved evolutionary sites. When compared with the frequency of missense mutations in 5545 X chromosomes from unaffected controls, we saw a statistically significant enrichment in patients with ASD (OR: 4.9; P < 0.014). In addition, we identified rare AFF2 3' UTR variants at conserved sites which alter gene expression in a luciferase assay. These data suggest that rare variation in AFF2 may be a previously unrecognized ASD susceptibility locus and may help explain some of the male excess of ASD. PMID- 22773737 TI - Targeted high-throughput sequencing for diagnosis of genetically heterogeneous diseases: efficient mutation detection in Bardet-Biedl and Alstrom syndromes. AB - BACKGROUND: Bardet-Biedl syndrome (BBS) is a pleiotropic recessive disorder that belongs to the rapidly growing family of ciliopathies. It shares phenotypic traits with other ciliopathies, such as Alstrom syndrome (ALMS), nephronophthisis (NPHP) or Joubert syndrome. BBS mutations have been detected in 16 different genes (BBS1-BBS16) without clear genotype-to-phenotype correlation. This extensive genetic heterogeneity is a major concern for molecular diagnosis and genetic counselling. While various strategies have been recently proposed to optimise mutation detection, they either fail to detect mutations in a majority of patients or are time consuming and costly. METHOD: We tested a targeted exon capture strategy coupled with multiplexing and high-throughput sequencing on 52 patients: 14 with known mutations as proof-of-principle and 38 with no previously detected mutation. Thirty genes were targeted in total including the 16 BBS genes, the 12 known NPHP genes, the single ALMS gene ALMS1 and the proposed modifier CCDC28B. RESULTS: This strategy allowed the reliable detection of causative mutations (including homozygous/heterozygous exon deletions) in 68% of BBS patients without previous molecular diagnosis and in all proof-of-principle samples. Three probands carried homozygous truncating mutations in ALMS1 confirming the major phenotypic overlap between both disorders. The efficiency of detecting mutations in patients was positively correlated with their compliance with the classical BBS phenotype (mutations were identified in 81% of 'classical' BBS patients) suggesting that only a few true BBS genes remain to be identified. We illustrate some interpretation problems encountered due to the multiplicity of identified variants. CONCLUSION: This strategy is highly efficient and cost effective for diseases with high genetic heterogeneity, and guarantees a quality of coverage in coding sequences of target genes suited for diagnosis purposes. PMID- 22773740 TI - Detection of macrolide resistance in Mycoplasma genitalium in France. AB - OBJECTIVES: Mycoplasma genitalium is a sexually transmitted organism associated with non-gonococcal urethritis in men and several inflammatory reproductive tract syndromes in women. Resistance to macrolides has been recently associated with point mutations in the 23S rRNA gene. The aim of this study was to detect these mutations using a large French collection of M. genitalium-positive specimens. We evaluated whether these mutations were related to azithromycin treatment failure and whether macrolide-resistant M. genitalium may be spreading. PATIENTS AND METHODS: A retrospective study conducted in France between 2003 and 2010 included 156 urogenital clinical specimens from 136 patients that were positive for M. genitalium. Mutations in domain V of M. genitalium 23S rRNA were detected using amplification and sequencing. The mutated strains were genotyped by studying single nucleotide polymorphisms in the mgpB gene. RESULTS: We have detected macrolide resistance-associated mutations in M. genitalium since 2006 at a rate of 13.2%, ranging from 10% to 15.4% of patients per year. Nine mutations at position 2059 as well as two A2058G substitutions, one A2062T substitution and one C2038T substitution (Escherichia coli numbering) were identified in M. genitalium. These patients had treatment failure with azithromycin in 75% (6/8) of cases. For one patient, genotyping showed selection for the mutation during treatment with azithromycin. CONCLUSIONS: For the first time, we describe macrolide resistance for M. genitalium in France and demonstrate that its detection has increased since 2006. Epidemiological surveillance of M. genitalium is necessary to adapt treatments to M. genitalium infections. PMID- 22773741 TI - Intrapulmonary penetration of ceftolozane/tazobactam and piperacillin/tazobactam in healthy adult subjects. AB - OBJECTIVES: Appropriate antibiotic exposure at the site of infection is important for clinically effective therapy. This study compared the epithelial lining fluid (ELF) penetration of ceftolozane/tazobactam, which has potent in vitro activity against many Gram-negative pathogens causing nosocomial pneumonia, with that of piperacillin/tazobactam in healthy adult volunteers. METHODS: In this Phase 1, open-label trial, 51 healthy adult subjects were randomized to receive three doses of either ceftolozane/tazobactam 1.5 g administered every 8 h via a 60 min infusion or piperacillin/tazobactam 4.5 g administered every 6 h via a 30 min infusion. Serial blood samples were obtained for determination of plasma drug concentrations. Bronchoscopy and bronchoalveolar lavage were performed at pre specified timepoints in five subjects per timepoint in each treatment group to determine the ELF drug concentration. The penetration of individual analytes into the ELF was determined from the ratio of the area under the plasma concentration time curve in ELF to that in plasma (AUC(ELF)/AUC(plasma)). RESULTS: Plasma and ELF concentrations of ceftolozane, piperacillin and tazobactam increased rapidly, reaching maximal concentrations at the end of the infusion. Mean maximum concentration and AUC from time 0 to the end of the dosing interval (AUC(0-tau)) for ceftolozane in ELF were 21.8 mg/L and 75.1 mg.h/L, respectively. Corresponding values for piperacillin were 58.8 mg/L and 94.5 mg.h/L. The ELF/plasma AUC ratio for ceftolozane was 0.48 compared with 0.26 for piperacillin. CONCLUSION: This study demonstrated that ceftolozane penetrated well into the ELF following parenteral administration of ceftolozane/tazobactam. PMID- 22773742 TI - Pharmacokinetic interaction between maraviroc and etravirine in HIV-infected patients receiving regimens containing both drugs and no ritonavir-boosted protease inhibitor. PMID- 22773743 TI - An auxin influx transporter regulates vascular patterning in cotyledons. PMID- 22773744 TI - Reconstitution of plant alkane biosynthesis in yeast demonstrates that Arabidopsis ECERIFERUM1 and ECERIFERUM3 are core components of a very-long-chain alkane synthesis complex. AB - In land plants, very-long-chain (VLC) alkanes are major components of cuticular waxes that cover aerial organs, mainly acting as a waterproof barrier to prevent nonstomatal water loss. Although thoroughly investigated, plant alkane synthesis remains largely undiscovered. The Arabidopsis thaliana ECERIFERUM1 (CER1) protein has been recognized as an essential element of wax alkane synthesis; nevertheless, its function remains elusive. In this study, a screen for CER1 physical interaction partners was performed. The screen revealed that CER1 interacts with the wax-associated protein ECERIFERUM3 (CER3) and endoplasmic reticulum-localized cytochrome b5 isoforms (CYTB5s). The functional relevance of these interactions was assayed through an iterative approach using yeast as a heterologous expression system. In a yeast strain manipulated to produce VLC acyl CoAs, a strict CER1 and CER3 coexpression resulted in VLC alkane synthesis. The additional presence of CYTB5s was found to enhance CER1/CER3 alkane production. Site-directed mutagenesis showed that CER1 His clusters are essential for alkane synthesis, whereas those of CER3 are not, suggesting that CYTB5s are specific CER1 cofactors. Collectively, our study reports the identification of plant alkane synthesis enzymatic components and supports a new model for alkane production in which CER1 interacts with both CER3 and CYTB5 to catalyze the redox dependent synthesis of VLC alkanes from VLC acyl-CoAs. PMID- 22773745 TI - An essential pentatricopeptide repeat protein facilitates 5' maturation and translation initiation of rps3 mRNA in maize mitochondria. AB - Pentatricopeptide repeat (PPR) proteins are members of one of the largest nucleus encoded protein families in plants. Here, we describe the previously uncharacterized maize (Zea mays) PPR gene, MPPR6, which was isolated from a Mutator-induced collection of maize kernel mutants by a cDNA-based forward genetic approach. Identification of a second mutant allele and cosegregation analysis confirmed correlation with the mutant phenotype. Histological investigations revealed that the mutation coincides with abnormities in the transfer cell layer, retardation of embryo development, and a considerable reduction of starch level. The function of MPPR6 is conserved across a wide phylogenetic distance as revealed by heterologous complementation of the Arabidopsis thaliana mutant in the orthologous APPR6 gene. MPPR6 appeared to be exclusively present in mitochondria. RNA coimmunoprecipitation and in vitro binding studies revealed a specific physical interaction of MPPR6 with the 5' untranslated region of ribosomal protein S3 (rps3) mRNA. Mapping of transcript termini showed specifically extended rps3 5' ends in the mppr6 mutant. Considerable reduction of mitochondrial translation was observed, indicating loss of RPS3 function. This is consistent with the appearance of truncated RPS3 protein lacking the N terminus in mppr6. Our results suggest that MPPR6 is directly involved in 5' maturation and translation initiation of rps3 mRNA. PMID- 22773746 TI - A flavin binding cryptochrome photoreceptor responds to both blue and red light in Chlamydomonas reinhardtii. AB - Cryptochromes are flavoproteins that act as sensory blue light receptors in insects, plants, fungi, and bacteria. We have investigated a cryptochrome from the green alga Chlamydomonas reinhardtii with sequence homology to animal cryptochromes and (6-4) photolyases. In response to blue and red light exposure, this animal-like cryptochrome (aCRY) alters the light-dependent expression of various genes encoding proteins involved in chlorophyll and carotenoid biosynthesis, light-harvesting complexes, nitrogen metabolism, cell cycle control, and the circadian clock. Additionally, exposure to yellow but not far red light leads to comparable increases in the expression of specific genes; this expression is significantly reduced in an acry insertional mutant. These in vivo effects are congruent with in vitro data showing that blue, yellow, and red light, but not far-red light, are absorbed by the neutral radical state of flavin in aCRY. The aCRY neutral radical is formed following blue light absorption of the oxidized flavin. Red illumination leads to conversion to the fully reduced state. Our data suggest that aCRY is a functionally important blue and red light activated flavoprotein. The broad spectral response implies that the neutral radical state functions as a dark form in aCRY and expands the paradigm of flavoproteins and cryptochromes as blue light sensors to include other light qualities. PMID- 22773747 TI - Evidence for a role of Arabidopsis CDT1 proteins in gametophyte development and maintenance of genome integrity. AB - Meristems retain the ability to divide throughout the life cycle of plants, which can last for over 1000 years in some species. Furthermore, the germline is not laid down early during embryogenesis but originates from the meristematic cells relatively late during development. Thus, accurate cell cycle regulation is of utmost importance to avoid the accumulation of mutations during vegetative growth and reproduction. The Arabidopsis thaliana genome encodes two homologs of the replication licensing factor CDC10 Target1 (CDT1), and overexpression of CDT1a stimulates DNA replication. Here, we have investigated the respective functions of Arabidopsis CDT1a and CDT1b. We show that CDT1 proteins have partially redundant functions during gametophyte development and are required for the maintenance of genome integrity. Furthermore, CDT1-RNAi plants show endogenous DNA stress, are more tolerant than the wild type to DNA-damaging agents, and show constitutive induction of genes involved in DNA repair. This DNA stress response may be a direct consequence of reduced CDT1 accumulation on DNA repair or may relate to the ability of CDT1 proteins to form complexes with DNA polymerase epsilon, which functions in DNA replication and in DNA stress checkpoint activation. Taken together, our results provide evidence for a crucial role of Arabidopsis CDT1 proteins in genome stability. PMID- 22773748 TI - Convergent starvation signals and hormone crosstalk in regulating nutrient mobilization upon germination in cereals. AB - Germination is a unique developmental transition from metabolically quiescent seed to actively growing seedling that requires an ensemble of hydrolases for coordinated nutrient mobilization to support heterotrophic growth until autotrophic photosynthesis is established. This study reveals two crucial transcription factors, MYBS1 and MYBGA, present in rice (Oryza sativa) and barley (Hordeum vulgare), that function to integrate diverse nutrient starvation and gibberellin (GA) signaling pathways during germination of cereal grains. Sugar represses but sugar starvation induces MYBS1 synthesis and its nuclear translocation. GA antagonizes sugar repression by enhancing conuclear transport of the GA-inducible MYBGA with MYBS1 and the formation of a stable bipartite MYB DNA complex to activate the alpha-amylase gene. We further discovered that not only sugar but also nitrogen and phosphate starvation signals converge and interconnect with GA to promote the conuclear import of MYBS1 and MYBGA, resulting in the expression of a large set of GA-inducible but functionally distinct hydrolases, transporters, and regulators associated with mobilization of the full complement of nutrients to support active seedling growth in cereals. PMID- 22773749 TI - AUX/LAX genes encode a family of auxin influx transporters that perform distinct functions during Arabidopsis development. AB - Auxin transport, which is mediated by specialized influx and efflux carriers, plays a major role in many aspects of plant growth and development. AUXIN1 (AUX1) has been demonstrated to encode a high-affinity auxin influx carrier. In Arabidopsis thaliana, AUX1 belongs to a small multigene family comprising four highly conserved genes (i.e., AUX1 and LIKE AUX1 [LAX] genes LAX1, LAX2, and LAX3). We report that all four members of this AUX/LAX family display auxin uptake functions. Despite the conservation of their biochemical function, AUX1, LAX1, and LAX3 have been described to regulate distinct auxin-dependent developmental processes. Here, we report that LAX2 regulates vascular patterning in cotyledons. We also describe how regulatory and coding sequences of AUX/LAX genes have undergone subfunctionalization based on their distinct patterns of spatial expression and the inability of LAX sequences to rescue aux1 mutant phenotypes, respectively. Despite their high sequence similarity at the protein level, transgenic studies reveal that LAX proteins are not correctly targeted in the AUX1 expression domain. Domain swapping studies suggest that the N-terminal half of AUX1 is essential for correct LAX localization. We conclude that Arabidopsis AUX/LAX genes encode a family of auxin influx transporters that perform distinct developmental functions and have evolved distinct regulatory mechanisms. PMID- 22773750 TI - Reproductive isolation during domestication. AB - It has been hypothesized that reproductive isolation should facilitate evolution under domestication. However, a systematic comparison of reproductive barrier strength between crops and their progenitors has not been conducted to test this hypothesis. Here, we present a systematic survey of reproductive barriers between 32 economically important crop species and their progenitors to better understand the role of reproductive isolation during the domestication process. We took a conservative approach, avoiding those types of reproductive isolation that are poorly known for these taxa (e.g., differences in flowering time). We show that the majority of crops surveyed are isolated from their progenitors by one or more reproductive barriers, despite the fact that the most important reproductive barrier in natural systems, geographical isolation, was absent, at least in the initial stages of domestication for most species. Thus, barriers to reproduction between crops and wild relatives are closely associated with domestication and may facilitate it, thereby raising the question whether reproductive isolation could be viewed as a long-overlooked "domestication trait." Some of the reproductive barriers observed (e.g., polyploidy and uniparental reproduction), however, may have been favored for reasons other than, or in addition to, their effects on gene flow. PMID- 22773751 TI - Genome-wide identification of regulatory DNA elements and protein-binding footprints using signatures of open chromatin in Arabidopsis. AB - Gene expression and regulation in eukaryotes is controlled by orchestrated binding of regulatory proteins, including both activators and repressors, to promoters and other cis-regulatory DNA elements. An increasing number of plant genomes have been sequenced; however, a similar effort to the ENCODE project, which aimed to identify all functional elements in the human genome, has yet to be initiated in plants. Here we report genome-wide high-resolution mapping of DNase I hypersensitive (DH) sites in the model plant Arabidopsis thaliana. We identified 38,290 and 41,193 DH sites in leaf and flower tissues, respectively. The DH sites were depleted of bulk nucleosomes and were tightly associated with RNA polymerase II binding sites. Approximately 90% of the binding sites of two well-characterized MADS domain transcription factors, APETALA1 and SEPALLATA3, were covered by the DH sites. We demonstrate that protein binding footprints within a specific genomic region can be revealed using the DH site data sets in combination with known or putative protein binding motifs and gene expression data sets. Thus, genome-wide DH site mapping will be an important tool for systematic identification of all cis-regulatory DNA elements in plants. PMID- 22773752 TI - BEX5/RabA1b regulates trans-Golgi network-to-plasma membrane protein trafficking in Arabidopsis. AB - Constitutive endocytic recycling is a crucial mechanism allowing regulation of the activity of proteins at the plasma membrane and for rapid changes in their localization, as demonstrated in plants for PIN-FORMED (PIN) proteins, the auxin transporters. To identify novel molecular components of endocytic recycling, mainly exocytosis, we designed a PIN1-green fluorescent protein fluorescence imaging-based forward genetic screen for Arabidopsis thaliana mutants that showed increased intracellular accumulation of cargos in response to the trafficking inhibitor brefeldin A (BFA). We identified bex5 (for BFA-visualized exocytic trafficking defective), a novel dominant mutant carrying a missense mutation that disrupts a conserved sequence motif of the small GTPase, RAS GENES FROM RAT BRAINA1b. bex5 displays defects such as enhanced protein accumulation in abnormal BFA compartments, aberrant endosomes, and defective exocytosis and transcytosis. BEX5/RabA1b localizes to trans-Golgi network/early endosomes (TGN/EE) and acts on distinct trafficking processes like those regulated by GTP exchange factors on ADP-ribosylation factors GNOM-LIKE1 and HOPM INTERACTOR7/BFA-VISUALIZED ENDOCYTIC TRAFFICKING DEFECTIVE1, which regulate trafficking at the Golgi apparatus and TGN/EE, respectively. All together, this study identifies Arabidopsis BEX5/RabA1b as a novel regulator of protein trafficking from a TGN/EE compartment to the plasma membrane. PMID- 22773753 TI - Zebrafish neurofibromatosis type 1 genes have redundant functions in tumorigenesis and embryonic development. AB - Neurofibromatosis type 1 (NF1) is a common, dominantly inherited genetic disorder that results from mutations in the neurofibromin 1 (NF1) gene. Affected individuals demonstrate abnormalities in neural-crest-derived tissues that include hyperpigmented skin lesions and benign peripheral nerve sheath tumors. NF1 patients also have a predisposition to malignancies including juvenile myelomonocytic leukemia (JMML), optic glioma, glioblastoma, schwannoma and malignant peripheral nerve sheath tumors (MPNSTs). In an effort to better define the molecular and cellular determinants of NF1 disease pathogenesis in vivo, we employed targeted mutagenesis strategies to generate zebrafish harboring stable germline mutations in nf1a and nf1b, orthologues of NF1. Animals homozygous for loss-of-function alleles of nf1a or nf1b alone are phenotypically normal and viable. Homozygous loss of both alleles in combination generates larval phenotypes that resemble aspects of the human disease and results in larval lethality between 7 and 10 days post fertilization. nf1-null larvae demonstrate significant central and peripheral nervous system defects. These include aberrant proliferation and differentiation of oligodendrocyte progenitor cells (OPCs), dysmorphic myelin sheaths and hyperplasia of Schwann cells. Loss of nf1 contributes to tumorigenesis as demonstrated by an accelerated onset and increased penetrance of high-grade gliomas and MPNSTs in adult nf1a(+/-); nf1b(-/ ); p53(e7/e7) animals. nf1-null larvae also demonstrate significant motor and learning defects. Importantly, we identify and quantitatively analyze a novel melanophore phenotype in nf1-null larvae, providing the first animal model of the pathognomonic pigmentation lesions of NF1. Together, these findings support a role for nf1a and nf1b as potent tumor suppressor genes that also function in the development of both central and peripheral glial cells as well as melanophores in zebrafish. PMID- 22773754 TI - Accelerated renal disease is associated with the development of metabolic syndrome in a glucolipotoxic mouse model. AB - Individuals with metabolic syndrome are at high risk of developing chronic kidney disease (CKD) through unclear pathogenic mechanisms. Obesity and diabetes are known to induce glucolipotoxic effects in metabolically relevant organs. However, the pathogenic role of glucolipotoxicity in the aetiology of diabetic nephropathy is debated. We generated a murine model, the POKO mouse, obtained by crossing the peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) knockout (KO) mouse into a genetically obese ob/ob background. We have previously shown that the POKO mice showed: hyperphagia, insulin resistance, hyperglycaemia and dyslipidaemia as early as 4 weeks of age, and developed a complete loss of normal beta-cell function by 16 weeks of age. Metabolic phenotyping of the POKO model has led to investigation of the structural and functional changes in the kidney and changes in blood pressure in these mice. Here we demonstrate that the POKO mouse is a model of renal disease that is accelerated by high levels of glucose and lipid accumulation. Similar to ob/ob mice, at 4 weeks of age these animals exhibited an increased urinary albumin:creatinine ratio and significantly increased blood pressure, but in contrast showed a significant increase in the renal hypertrophy index and an associated increase in p27(Kip1) expression compared with their obese littermates. Moreover, at 4 weeks of age POKO mice showed insulin resistance, an alteration of lipid metabolism and glomeruli damage associated with increased transforming growth factor beta (TGFbeta) and parathyroid hormone-related protein (PTHrP) expression. At this age, levels of proinflammatory molecules, such as monocyte chemoattractant protein-1 (MCP-1), and fibrotic factors were also increased at the glomerular level compared with levels in ob/ob mice. At 12 weeks of age, renal damage was fully established. These data suggest an accelerated lesion through glucolipotoxic effects in the renal pathogenesis in POKO mice. PMID- 22773755 TI - Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice. AB - Mutations in SPG4, encoding the microtubule-severing protein spastin, are responsible for the most frequent form of hereditary spastic paraplegia (HSP), a heterogeneous group of genetic diseases characterized by degeneration of the corticospinal tracts. We previously reported that mice harboring a deletion in Spg4, generating a premature stop codon, develop progressive axonal degeneration characterized by focal axonal swellings associated with impaired axonal transport. To further characterize the molecular and cellular mechanisms underlying this mutant phenotype, we have assessed microtubule dynamics and axonal transport in primary cultures of cortical neurons from spastin-mutant mice. We show an early and marked impairment of microtubule dynamics all along the axons of spastin-deficient cortical neurons, which is likely to be responsible for the occurrence of axonal swellings and cargo stalling. Our analysis also reveals that a modulation of microtubule dynamics by microtubule targeting drugs rescues the mutant phenotype of cortical neurons. Together, these results contribute to a better understanding of the pathogenesis of SPG4-linked HSP and ascertain the influence of microtubule-targeted drugs on the early axonal phenotype in a mouse model of the disease. PMID- 22773757 TI - Reduced bone morphogenetic protein receptor type 1A signaling in neural-crest derived cells causes facial dysmorphism. AB - Bone morphogenetic protein (BMP) receptor type 1A (BMPR1A) mutations are associated with facial dysmorphism, which is one of the main clinical signs in both juvenile polyposis and chromosome 10q23 deletion syndromes. Craniofacial development requires reciprocal epithelial/neural crest (NC)-derived mesenchymal interactions mediated by signaling factors, such as BMP, in both cell populations. To address the role of mesenchymal BMP signaling in craniofacial development, we generated a conditional knockdown mouse by expressing the dominant-negative Bmpr1a in NC-derived cells expressing the myelin protein zero(Mpz)-Cre transgene. At birth, 100% of the conditional mutant mice had wide open anterior fontanelles, and 80% of them died because of cleft face and cleft palate soon after birth. The other 20% survived and developed short faces, hypertelorism and calvarial foramina. Analysis of the NC-derived craniofacial mesenchyme of mutant embryos revealed an activation of the P53 apoptosis pathway, downregulation of both c-Myc and Bcl-XL, a normal growth rate but an incomplete expansion of mesenchymal cells. These findings provide genetic evidence indicating that optimal Bmpr1a-mediated signaling is essential for NC-derived mesenchymal cell survival in both normal nasal and frontal bone development and suggest that our model is useful for studying some aspects of the molecular etiology of human craniofacial dysmorphism. PMID- 22773756 TI - Postnatal maternal separation modifies the response to an obesogenic diet in adulthood in rats. AB - An early-life adverse environment has been implicated in the susceptibility to different diseases in adulthood, such as mental disorders, diabetes and obesity. We analyzed the effects of a high-fat sucrose (HFS) diet for 35 days in adult female rats that had experienced 180 minutes daily of maternal separation (MS) during lactancy. Changes in the obesity phenotype, biochemical profile, levels of glucocorticoid metabolism biomarkers, and the expression of different obesity- and glucocorticoid-metabolism-related genes were analyzed in periovaric adipose tissue. HFS intake increased body weight, adiposity and serum leptin levels, whereas MS decreased fat pad masses but only in rats fed an HFS diet. MS reduced insulin resistance markers but only in chow-fed rats. Corticosterone and estradiol serum levels did not change in this experimental model. A multiple gene expression analysis revealed that the expression of adiponutrin (Adpn) was increased owing to MS, and an interaction between HFS diet intake and MS was observed in the mRNA levels of leptin (Lep) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1a). These results revealed that early life stress affects the response to an HFS diet later in life, and that this response can lead to phenotype and transcriptomic changes. PMID- 22773760 TI - Primary care physicians surveyed in this study mistakenly interpreted improved survival and increased detection with screening as evidence that screening saves lives. PMID- 22773759 TI - The rice monovalent cation transporter OsHKT2;4: revisited ionic selectivity. AB - The family of plant membrane transporters named HKT (for high-affinity K(+) transporters) can be subdivided into subfamilies 1 and 2, which, respectively, comprise Na(+)-selective transporters and transporters able to function as Na(+) K(+) symporters, at least when expressed in yeast (Saccharomyces cerevisiae) or Xenopus oocytes. Surprisingly, a subfamily 2 member from rice (Oryza sativa), OsHKT2;4, has been proposed to form cation/K(+) channels or transporters permeable to Ca(2+) when expressed in Xenopus oocytes. Here, OsHKT2;4 functional properties were reassessed in Xenopus oocytes. A Ca(2+) permeability through OsHKT2;4 was not detected, even at very low external K(+) concentration, as shown by highly negative OsHKT2;4 zero-current potential in high Ca(2+) conditions and lack of sensitivity of OsHKT2;4 zero-current potential and conductance to external Ca(2+). The Ca(2+) permeability previously attributed to OsHKT2;4 probably resulted from activation of an endogenous oocyte conductance. OsHKT2;4 displayed a high permeability to K(+) compared with that to Na(+) (permeability sequence: K(+) > Rb(+) ~ Cs(+) > Na(+) ~ Li(+) ~ NH(4)(+)). Examination of OsHKT2;4 current sensitivity to external pH suggested that H(+) is not significantly permeant through OsHKT2;4 in most physiological ionic conditions. Further analyses in media containing both Na(+) and K(+) indicated that OsHKT2;4 functions as K(+)-selective transporter at low external Na(+), but transports also Na(+) at high (>10 mm) Na(+) concentrations. These data identify OsHKT2;4 as a new functional type in the K(+) and Na(+)-permeable HKT transporter subfamily. Furthermore, the high permeability to K(+) in OsHKT2;4 supports the hypothesis that this system is dedicated to K(+) transport in the plant. PMID- 22773758 TI - Oxidative stress contributes to outcome severity in a Drosophila melanogaster model of classic galactosemia. AB - Classic galactosemia is a genetic disorder that results from profound loss of galactose-1P-uridylyltransferase (GALT). Affected infants experience a rapid escalation of potentially lethal acute symptoms following exposure to milk. Dietary restriction of galactose prevents or resolves the acute sequelae; however, many patients experience profound long-term complications. Despite decades of research, the mechanisms that underlie pathophysiology in classic galactosemia remain unclear. Recently, we developed a Drosophila melanogaster model of classic galactosemia and demonstrated that, like patients, GALT-null Drosophila succumb in development if exposed to galactose but live if maintained on a galactose-restricted diet. Prior models of experimental galactosemia have implicated a possible association between galactose exposure and oxidative stress. Here we describe application of our fly genetic model of galactosemia to the question of whether oxidative stress contributes to the acute galactose sensitivity of GALT-null animals. Our first approach tested the impact of pro- and antioxidant food supplements on the survival of GALT-null and control larvae. We observed a clear pattern: the oxidants paraquat and DMSO each had a negative impact on the survival of mutant but not control animals exposed to galactose, and the antioxidants vitamin C and alpha-mangostin each had the opposite effect. Biochemical markers also confirmed that galactose and paraquat synergistically increased oxidative stress on all cohorts tested but, interestingly, the mutant animals showed a decreased response relative to controls. Finally, we tested the expression levels of two transcripts responsive to oxidative stress, GSTD6 and GSTE7, in mutant and control larvae exposed to galactose and found that both genes were induced, one by more than 40-fold. Combined, these results implicate oxidative stress and response as contributing factors in the acute galactose sensitivity of GALT-null Drosophila and, by extension, suggest that reactive oxygen species might also contribute to the acute pathophysiology in classic galactosemia. PMID- 22773761 TI - A 10-day course of amoxicillin does not reduce symptoms of acute rhinosinusitis at day 3 of treatment. PMID- 22773762 TI - Single-tablet double-dose famotidine plus ibuprofen decreases endoscopic upper GI ulcers compared with ibuprofen alone. PMID- 22773763 TI - Steroid injection and regular shoulder-specific exercises reduce the need for surgery in subacromial impingement syndrome. PMID- 22773764 TI - High-sensitivity troponin useful for diagnosis and prognosis in patients with acute coronary syndrome. PMID- 22773765 TI - Review of evidence concerning PSA screening for prostate cancer has limitations as basis for policy development. PMID- 22773766 TI - Myocardial accumulation and localization of the inducible 70-kDa heat shock protein, Hsp70, following exercise. AB - Exercise increases the 70-kDa heat shock protein (Hsp70) in the myocardium, and this exercise-induced increase is associated with significantly improved cardiac recovery following insult. However, while heat shock has been shown to elevate Hsp70 primarily in the cardiac vasculature of the myocardium, the localization following exercise is unknown. Male Sprague-Dawley rats performed continuous treadmill running at 30 m/min for 60 min (2% incline) on either 1 or 5 consecutive days. At 30 min and 24 h following exercise, hearts were extirpated, and the left ventricle was isolated, OCT-cork mounted, and sectioned for immunofluorescent analysis. Whereas immunofluorescent analysis revealed little to no Hsp70 in control hearts and 30 min postexercise, the accumulation of Hsp70 24 h after a single exercise bout or 5 days of training was predominantly located in large blood vessels and, in particular, colocalized with a marker of smooth muscle. Furthermore, higher core temperatures attained during exercise led to more abundant accumulation in smaller vessels and the endothelium. It is concluded that the accumulation of myocardial Hsp70 following acute exercise predominantly occurs in a cell type-specific manner, such that changes in the cardiac vasculature account for much of the increase. This accumulation appears first in the smooth muscle of larger vessels and then increases in smaller vessels and the endothelium, as core temperature attained during exercise increases. This finding supports the observations after heat shock and further suggests that the vasculature is a primary target in exercise-induced cardioprotection. PMID- 22773768 TI - Dietary nitrate improves muscle but not cerebral oxygenation status during exercise in hypoxia. AB - Exercise tolerance is impaired in hypoxia, and it has recently been shown that dietary nitrate supplementation can reduce the oxygen (O(2)) cost of muscle contractions. Therefore, we investigated the effect of dietary nitrate supplementation on arterial, muscle, and cerebral oxygenation status, symptoms of acute mountain sickness (AMS), and exercise tolerance at simulated 5,000 m altitude. Fifteen young, healthy volunteers participated in three experimental sessions according to a crossover study design. From 6 days prior to each session, subjects received either beetroot (BR) juice delivering 0.07 mmol nitrate/kg body wt/day or a control drink (CON). One session was in normoxia with CON (NOR(CON)); the two other sessions were in hypoxia (11% O(2)), with either CON (HYP(CON)) or BR (HYP(BR)). Subjects first cycled for 20 min at 45% of peak O(2) consumption (VO(2)peak; EX(45%)) and thereafter, performed a maximal incremental exercise test (EX(max)). Whole-body VO(2), arterial O(2) saturation (%SpO(2)) via pulsoximetry, and tissue oxygenation index of both muscle (TOI(M)) and cerebral (TOI(C)) tissue by near-infrared spectroscopy were measured. Hypoxia per se substantially reduced VO(2)peak, %SpO(2), TOI(M), and TOI(C) (NOR(CON) vs. HYP(CON), P < 0.05). Compared with HYP(CON), VO(2) at rest and during EX(45%) was lower in HYP(BR) (P < 0.05), whereas %SpO(2) was higher (P < 0.05). TOI(M) was ~4 5% higher in HYP(BR) than in HYP(CON) both at rest and during EX(45%) and EX(max) (P < 0.05). TOI(C) as well as the incidence of AMS symptoms were similar between HYP(CON) and HYP(BR) at any time. Hypoxia reduced time to exhaustion in EX(max) by 36% (P < 0.05), but this ergolytic effect was partly negated by BR (+5%, P < 0.05). Short-term dietary nitrate supplementation improves arterial and muscle oxygenation status but not cerebral oxygenation status during exercise in severe hypoxia. This is associated with improved exercise tolerance against the background of a similar incidence of AMS. PMID- 22773767 TI - Ventilation-perfusion distribution in normal subjects. AB - Functional values of LogSD of the ventilation distribution (sigma(V)) have been reported previously, but functional values of LogSD of the perfusion distribution (sigma(q)) and the coefficient of correlation between ventilation and perfusion (rho) have not been measured in humans. Here, we report values for sigma(V), sigma(q), and rho obtained from wash-in data for three gases, helium and two soluble gases, acetylene and dimethyl ether. Normal subjects inspired gas containing the test gases, and the concentrations of the gases at end-expiration during the first 10 breaths were measured with the subjects at rest and at increasing levels of exercise. The regional distribution of ventilation and perfusion was described by a bivariate log-normal distribution with parameters sigma(V), sigma(q), and rho, and these parameters were evaluated by matching the values of expired gas concentrations calculated for this distribution to the measured values. Values of cardiac output and LogSD ventilation/perfusion (Va/Q) were obtained. At rest, sigma(q) is high (1.08 +/- 0.12). With the onset of ventilation, sigma(q) decreases to 0.85 +/- 0.09 but remains higher than sigma(V) (0.43 +/- 0.09) at all exercise levels. Rho increases to 0.87 +/- 0.07, and the value of LogSD Va/Q for light and moderate exercise is primarily the result of the difference between the magnitudes of sigma(q) and sigma(V). With known values for the parameters, the bivariate distribution describes the comprehensive distribution of ventilation and perfusion that underlies the distribution of the Va/Q ratio. PMID- 22773769 TI - Effects of transdermal estrogen on collagen turnover at rest and in response to exercise in postmenopausal women. AB - Menopause is associated with loss of collagen content in the skin and tendon as well as accumulation of noncontractile tissue in skeletal muscle. The relative role of hormones and physical activity on these changes is not known. Accordingly, in a randomized, controlled, crossover study we investigated effects of transdermal estrogen replacement therapy (ERT) on type I collagen synthesis in tendon and skeletal muscle in 11 postmenopausal women. Patches with estrogen (Evorel) were placed on the skin above the patellar tendons and compared with no patch (control period). On day 2 all subjects performed one-legged exercise, and thereafter the exercised leg (EX leg) was compared with the nonexercised leg (Rest leg). Microdialysis catheters were placed in front of the patellar tendons and in the vastus lateralis muscle of both legs at days 3 and 5. The collected dialysate was analyzed for procollagen type I NH(2)-terminal propeptide (PINP), insulin-like growth factor I (IGF-I), and interleukin-6 (IL-6). Neither loading (Rest leg vs. EX leg) nor treatment (control vs. ERT) influenced peritendinous PINP, whereas combined exercise and ERT enhanced muscle PINP after 72 h (interaction between loading and treatment P = 0.008). In neither skeletal muscle nor peritendinous fluid were IGF-I and IL-6 influenced by treatment or exercise. In conclusion, ERT was associated with enhanced synthesis of type I collagen in the skeletal muscle in response to acute exercise. In perspective, this indicates that the availability of estrogen in postmenopausal women is important for repair of muscle damage or remodeling of the connective tissue within the skeletal muscle after exercise. PMID- 22773771 TI - Static and dynamic imaging of alveoli using optical coherence tomography needle probes. AB - Imaging of alveoli in situ has for the most part been infeasible due to the high resolution required to discern individual alveoli and limited access to alveoli beneath the lung surface. In this study, we present a novel technique to image alveoli using optical coherence tomography (OCT). We propose the use of OCT needle probes, where the distal imaging probe has been miniaturized and encased within a hypodermic needle (as small as 30-gauge, outer diameter 310 MUm), allowing insertion deep within the lung tissue with minimal tissue distortion. Such probes enable imaging at a resolution of ~12 MUm within a three-dimensional cylindrical field of view with diameter ~1.5 mm centered on the needle tip. The imaging technique is demonstrated on excised lungs from three different species: adult rats, fetal sheep, and adult pigs. OCT needle probes were used to image alveoli, small bronchioles, and blood vessels, and results were matched to histological sections. We also present the first dynamic OCT images acquired with an OCT needle probe, allowing tracking of individual alveoli during simulated cyclical lung inflation and deflation. PMID- 22773770 TI - Chronic intermittent hypoxia exposure improves left ventricular contractility in transgenic mice with heart failure. AB - We previously reported the unexpected finding that 4 wk of exposure to intermittent hypoxia (IH), which simulates the hypoxic stress of obstructive sleep apnea, improved LV cardiac function in healthy, lean C57BL/6J mice. The purpose of the present study was to assess the impact of 4 wk of IH on cardiac function in a transgenic murine model that exhibits a natural history of heart failure. We hypothesized that IH exposure would exacerbate cardiac decompensation in heart failure. Adult male FVB (wild type) and transgenic mice with cardiac overexpression of tumor necrosis factor alpha (TNF-alphaTG) at 10-12 wk of age were exposed to 4 wk of IH (nadir inspired oxygen 5-6% at 60 cycles/h for 12 h during light period) or intermittent air (IA) as control. Cardiac function was assessed by echocardiography and pressure-volume loop analyses, and mRNA and protein expression were performed on ventricular homogenates. TNF-alphaTG mice exposed to IA exhibited impaired LV contractility and increased LV dilation associated with markedly elevated cardiac expression of atrial natriuretic peptide and brain natriuretic peptide compared with wild-type mice. When wild type FVB mice were exposed to IH, they exhibited increases in arterial pressure and dP/dt(max), consistent with our previous report in C57BL/6J mice. Surprisingly, we found that TNF-alphaTG mice exposed to IH showed a reduction in end-diastolic volume (38.7 +/- 3.8 to 22.2 +/- 2.1 ul; P < 0.01) and an increase in ejection fraction (29.4 +/- 2.5 to 41.9 +/- 3.1%; P < 0.05). In contrast to our previous study in C56Bl/6J mice, neither FVB nor TNF-alphaTG mice exhibited an upregulation in beta-adrenergic expression or cAMP in response to IH exposure. We conclude that 4 wk of exposure to IH in mice induces adaptive responses that improve cardiac function in not only healthy animals but also in animals with underlying heart failure. PMID- 22773772 TI - Impact of hydroxyl radical-induced injury on calcium handling and myofilament sensitivity in isolated myocardium. AB - Hydroxyl radicals (OH) are involved in the pathogenesis of reperfusion injury and are observed in acute heart failure, stroke, and myocardial infarction. Two different subcellular defects are involved in the pathogenesis of OH injury, deranged calcium handling, and alterations of myofilament responsiveness, but their temporal impact on contractile function is not resolved. Initially, after brief OH exposure, there is a corresponding marked increase in diastolic calcium and diastolic force. We followed these parameters until a new steady-state level was reached at ~45 min post-OH exposure. At this new baseline, diastolic calcium had returned to near-normal, pre-OH levels, whereas diastolic force remained markedly elevated. An increased calcium sensitivity was observed at the new baseline after OH-induced injury compared with the pre-OH state. The acute injury that occurs after OH exposure is mainly due to calcium overload, while the later sustained myocardial dysfunction is mainly due to the altered/increased myofilament responsiveness. PMID- 22773774 TI - Intracellular Na(+) and metabolic modulation of Na/K pump and excitability in the rat suprachiasmatic nucleus neurons. AB - Na/K pump activity and metabolic rate are both higher during the day in the suprachiasmatic nucleus (SCN) that houses the circadian clock. Here we investigated the role of intracellular Na(+) and energy metabolism in regulating Na/K pump activity and neuronal excitability. Removal of extracellular K(+) to block the Na/K pump excited SCN neurons to fire at higher rates and return to normal K(+) to reactivate the pump produced rebound hyperpolarization to inhibit firing. In the presence of tetrodotoxin to block the action potentials, both zero K(+)-induced depolarization and rebound hyperpolarization were blocked by the cardiac glycoside strophanthidin. Ratiometric Na(+) imaging with a Na(+) sensitive fluorescent dye indicated saturating accumulation of intracellular Na(+) in response to pump blockade with zero K(+). The Na(+) ionophore monensin also induced Na(+) loading and hyperpolarized the membrane potential, with the hyperpolarizing effect of monensin abolished in zero Na(+) or by pump blockade. Conversely, Na(+) depletion with Na(+)-free pipette solution depolarized membrane potential but retained residual Na/K pump activity. Cyanide inhibition of oxidative phosphorylation blocked the Na/K pump to depolarize resting potential and increase spontaneous firing in most cells, and to raise intracellular Na(+) levels in all cells. Nonetheless, the Na/K pump was incompletely blocked by cyanide but completely blocked by iodoacetate to inhibit glycolysis, indicating the involvement of both oxidative phosphorylation and glycolysis in fueling the Na/K pump. Together, the results indicate the importance of intracellular Na(+) and energy metabolism in regulating Na/K pump activity as well as neuronal excitability in the SCN neurons. PMID- 22773773 TI - Central neuromodulatory pathways regulating sympathetic activity in hypertension. AB - The classical neurotransmitters, glutamate and GABA, mediate fast (milliseconds) synaptic transmission and modulate its effectiveness through slow (seconds to minutes) signaling processes. Angiotensinergic pathways, from the lamina terminalis to the paraventricular nucleus (PVN)/supraoptic nucleus and rostral ventrolateral medulla (RVLM), are activated by stimuli such as circulating angiotensin type II (Ang II), cerebrospinal fluid (CSF) sodium ion concentration ([Na(+)]), and possibly plasma aldosterone, leading to sympathoexcitation, largely by decreasing GABA and increasing glutamate release. The aldosterone endogenous ouabain (EO) pathway is a much slower neuromodulatory pathway. Aldosterone enhances EO release, and the latter increases chronic activity in angiotensinergic pathways by, e.g., increasing expression for Ang I receptor (AT(1)R) and NADPH oxidase subunits in the PVN. Blockade of this pathway does not affect the initial sympathoexcitatory and pressor responses but to a large extent, prevents chronic responses to CSF [Na(+)] or Ang II. Recruitment of these two neuromodulatory pathways allows the central nervous system (CNS) to shift gears to rapidly cause and sustain sympathetic hyperactivity in an efficient manner. Decreased GABA release, increased glutamate release, and enhanced AT(1)R activation in, e.g., the PVN and RVLM contribute to the elevated blood pressure in a number of hypertension models. In Dahl S rats and spontaneous hypertensive rats, high salt activates the CNS aldosterone-EO pathway, and the salt-induced hypertension can be prevented/reversed by specific CNS blockade of any of the steps in the cascade from aldosterone synthase to AT(1)R. Further studies are needed to advance our understanding of how and where in the brain these rapid, slow, and very slow CNS pathways are activated and interact in models of hypertension and other disease states associated with chronic sympathetic hyperactivity. PMID- 22773775 TI - Receptive field properties and intensity-response functions of polarization sensitive neurons of the optic tubercle in gregarious and solitarious locusts. AB - Many migrating insects rely on the plane of sky polarization as a cue to detect spatial directions. Desert locusts (Schistocerca gregaria), like other insects, perceive polarized light through specialized photoreceptors in a dorsal eye region. Desert locusts occur in two phases: a gregarious swarming phase, which migrates during the day, and a solitarious nocturnal phase. Neurons in a small brain area, the anterior optic tubercle (AOTu), are critically involved in processing polarized light in the locust brain. While polarization-sensitive intertubercle cells [lobula-tubercle neuron 1 (LoTu1) and tubercle-tubercle neuron 1 (TuTu1)] interconnect the AOTu of both hemispheres, tubercle-lateral accessory lobe tract (TuLAL1) neurons transmit sky compass signals to a polarization compass in the central brain. To better understand the neural network underlying polarized light processing in the AOTu and to investigate possible adaptations of the polarization vision system to a diurnal versus nocturnal lifestyle, we analyzed receptive field properties, intensity-response relationships, and daytime dependence of responses of AOTu neurons in gregarious and solitarious locusts. Surprisingly, no differences in the physiology of these neurons were found between the two locust phases. Instead, clear differences were observed between the different types of AOTu neurons. Whereas TuTu1 and TuLAL1 neurons encoded E-vector orientation independent of light intensity and would thus be operational in bright daylight, LoTu1 neurons were inhibited by high light intensity and provided strong polarization signaling only under dim light conditions. The presence of high- and low-intensity polarization channels might, therefore, allow solitarious and gregarious locusts to use the same polarization coding system despite their different activity cycles. PMID- 22773776 TI - The modulatory influence of end-point controllability on decisions between actions. AB - Recent work has shown that human subjects are able to predict the biomechanical ease of potential reaching movements and use these predictions to influence their choices. Here, we examined how reach decisions are influenced by specific biomechanical factors related to the control of end-point stability, such as aiming accuracy or stopping control. Human subjects made free choices between two potential reaching movements that varied in terms of path distance and biomechanical cost in four separate blocks that additionally varied two constraints: the width of the targets (narrow or wide) and the requirement of stopping in them. When movements were unconstrained (very wide targets and no requirement of stopping), subjects' choices were strongly biased toward directions aligned with the direction of maximal mobility. However, as the movements became progressively constrained, factors related to the control of the end point gained relevance, thus reducing this bias. This demonstrates that, before movement onset, constraints such as stopping and aiming participate in a remarkably adaptive and flexible action selection process that trades off the advantage of moving along directions of maximal mobility for unconstrained movements against exploiting biomechanical anisotropies to facilitate control of end-point stability whenever the movement constraints require it. These results support a view of decision making between motor actions as a highly context dependent gradual process in which the subjective desirability of potential actions is influenced by their dynamic properties in relation to the intrinsic properties of the motor apparatus. PMID- 22773777 TI - Adaptive coding is constrained to midline locations in a spatial listening task. AB - Many neurons adapt their spike output to accommodate the prevailing sensory environment. Although such adaptation is thought to improve coding of relevant stimulus features, the relationship between adaptation at the neural and behavioral levels remains to be established. Here we describe improved discrimination performance for an auditory spatial cue (interaural time differences, ITDs) following adaptation to stimulus statistics. Physiological recordings in the midbrain of anesthetized guinea pigs and measurement of discrimination performance in humans both demonstrate improved coding of the most prevalent ITDs in a distribution, but with highest accuracy maintained for ITDs corresponding to frontal locations, suggesting the existence of a fovea for auditory space. A biologically plausible model accounting for the physiological data suggests that neural tuning is stabilized by inhibition to maintain high discriminability for frontal locations. The data support the notion that adaptive coding in the midbrain is a key element of behaviorally efficient sound localization in dynamic acoustic environments. PMID- 22773778 TI - beta- And gamma-band EEG power predicts illusory auditory continuity perception. AB - Because acoustic landscapes are complex and rapidly changing, auditory systems have evolved mechanisms that permit rapid detection of novel sounds, sound source segregation, and perceptual restoration of sounds obscured by noise. Perceptual restoration is particularly important in noisy environments because it allows organisms to track sounds over time even when they are masked. The continuity illusion is a striking example of perceptual restoration with sounds perceived as intact even when parts of them have been replaced by gaps and rendered inaudible by being masked by an extraneous sound. The mechanisms of auditory filling-in are complex and are currently not well-understood. The present study used the high temporal resolution of EEG to examine brain activity related to continuity illusion perception. Masking noise loudness was adjusted individually for each subject so that physically identical sounds on some trials elicited a continuity illusion (failure to detect a gap in a sound) and on other trials resulted in correct gap detection. This design ensured that any measurable differences in brain activity would be due to perceptual differences rather than physical differences among stimuli. We found that baseline activity recorded immediately before presentation of the stimulus significantly predicted the occurrence of the continuity illusion in 10 out of 14 participants based on power differences in gamma-band EEG (34-80 Hz). Across all participants, power in the beta and gamma (12- to 80-Hz range) was informative about the subsequent perceptual decision. These data suggest that a subject's baseline brain state influences the strength of continuity illusions. PMID- 22773779 TI - Selective bilateral activation of leg muscles after cutaneous nerve stimulation during backward walking. AB - During human locomotion, cutaneous reflexes have been suggested to function to preserve balance. Specifically, cutaneous reflexes in the contralateral leg's muscles (with respect to the stimulus) were suggested to play an important role in maintaining stability during locomotor tasks where stability is threatened. We used backward walking (BW) as a paradigm to induce unstable gait and analyzed the cutaneous reflex activity in both ipsilateral and contralateral lower limb muscles after stimulation of the sural nerve at different phases of the gait cycle. In BW, the tibialis anterior (TA) reflex activity in the contralateral leg was markedly higher than TA background EMG activity during its stance phase. In addition, in BW a substantial reflex suppression was observed in the ipsilateral biceps femoris during the stance-swing transition in some participants, while for medial gastrocnemius the reflex activity was equal to background activity in both legs. To test whether the pronounced crossed responses in TA could be related to instability, the responses were correlated with measures of stability (short-term maximum Lyapunov exponents and step width). These measures were higher for BW compared with forward walking, indicating that BW is less stable. However, there was no significant correlation between these measures and the amplitude of the crossed TA responses in BW. It is therefore proposed that these crossed responses are related to an attempt to briefly slow down (TA decelerates the center of mass in the single-stance period) in the light of unexpected perturbations, such as provided by the sural nerve stimulation. PMID- 22773780 TI - Hand-held tools with complex kinematics are efficiently incorporated into movement planning and online control. AB - Certain hand-held tools alter the mapping between hand motion and motion of the tool end point that must be controlled in order to perform a task. For example, when using a pool cue, the motion of the cue tip is reversed relative to the hand. Previous studies have shown that the time required to initiate a reaching movement (Fernandez-Ruiz J, Wong W, Armstrong IT, Flanagan JR. Behav Brain Res 219: 8-14, 2011), or correct an ongoing reaching movement (Gritsenko V, Kalaska JF. J Neurophysiol 104: 3084-3104, 2010), is prolonged when the mapping between hand motion and motion of a cursor controlled by the hand is reversed. Here we show that these time costs can be significantly reduced when the reversal is instantiated by a virtual hand-held tool. Participants grasped the near end of a virtual tool, consisting of a rod connecting two circles, and moved the end point to displayed targets. In the reversal condition, the rod translated through, and rotated about, a pivot point such that there was a left-right reversal between hand and end point motion. In the nonreversal control, the tool translated with the hand. As expected, when only the two circles were presented, movement initiation and correction times were much longer in the reversal condition. However, when full vision of the tool was provided, the reaction time cost was almost eliminated. These results indicate that tools with complex kinematics can be efficiently incorporated into sensorimotor control mechanisms used in movement planning and online control. PMID- 22773782 TI - Sensitivity to prediction error in reach adaptation. AB - It has been proposed that the brain predicts the sensory consequences of a movement and compares it to the actual sensory feedback. When the two differ, an error signal is formed, driving adaptation. How does an error in one trial alter performance in the subsequent trial? Here we show that the sensitivity to error is not constant but declines as a function of error magnitude. That is, one learns relatively less from large errors compared with small errors. We performed an experiment in which humans made reaching movements and randomly experienced an error in both their visual and proprioceptive feedback. Proprioceptive errors were created with force fields, and visual errors were formed by perturbing the cursor trajectory to create a visual error that was smaller, the same size, or larger than the proprioceptive error. We measured single-trial adaptation and calculated sensitivity to error, i.e., the ratio of the trial-to-trial change in motor commands to error size. We found that for both sensory modalities sensitivity decreased with increasing error size. A reanalysis of a number of previously published psychophysical results also exhibited this feature. Finally, we asked how the brain might encode sensitivity to error. We reanalyzed previously published probabilities of cerebellar complex spikes (CSs) and found that this probability declined with increasing error size. From this we posit that a CS may be representative of the sensitivity to error, and not error itself, a hypothesis that may explain conflicting reports about CSs and their relationship to error. PMID- 22773781 TI - Decreased afferent excitability contributes to synaptic depression during high frequency stimulation in hippocampal area CA1. AB - Long-term potentiation (LTP) is often induced experimentally by continuous high frequency afferent stimulation (HFS), typically at 100 Hz for 1 s. Induction of LTP requires postsynaptic depolarization and voltage-dependent calcium influx. Induction is more effective if the same number of stimuli are given as a series of short bursts rather than as continuous HFS, in part because excitatory postsynaptic potentials (EPSPs) become strongly depressed during HFS, reducing postsynaptic depolarization. In this study, we examined mechanisms of EPSP depression during HFS in area CA1 of rat hippocampal brain slices. We tested for presynaptic terminal vesicle depletion by examining minimal stimulation-evoked excitatory postsynaptic currents (EPSCs) during 100-Hz HFS. While transmission failures increased, consistent with vesicle depletion, EPSC latencies also increased during HFS, suggesting a decrease in afferent excitability. Extracellular recordings of Schaffer collateral fiber volleys confirmed a decrease in afferent excitability, with decreased fiber volley amplitudes and increased latencies during HFS. To determine the mechanism responsible for fiber volley changes, we recorded antidromic action potentials in single CA3 pyramidal neurons evoked by stimulating Schaffer collateral axons. During HFS, individual action potentials decreased in amplitude and increased in latency, and these changes were accompanied by a large increase in the probability of action potential failure. Time derivative and phase-plane analyses indicated decreases in both axon initial segment and somato-dendritic components of CA3 neuron action potentials. Our results indicate that decreased presynaptic axon excitability contributes to depression of excitatory synaptic transmission during HFS at synapses between Schaffer collaterals and CA1 pyramidal neurons. PMID- 22773784 TI - SPARX computerised CBT is as effective as usual care for mild-to-moderate depression in help seeking adolescents. PMID- 22773783 TI - Modular organization of balance control following perturbations during walking. AB - Balance recovery during walking requires complex sensory-motor integration. Mechanisms to avoid falls are active concomitantly with human locomotion motor patterns. It has been suggested that gait can be described by a set of motor modules (synergies), but little is known on the modularity of gait during recovery of balance due to unexpected slips. Our hypothesis was that muscular activation during reactive recovery of balance during gait has a modular organization. The aim of the study was to verify this hypothesis when perturbations were delivered in different directions. Eight healthy men walked on a 7-m walkway, which had a moveable force platform embedded in the middle. Subjects experienced unperturbed walking as well as perturbations delivered in the sagittal (forward and backward) and frontal (leftward and rightward) planes. Bilateral full-body kinematics and surface electromyography (EMG) from lower limbs, trunk, and neck were recorded during walking. Synergies and activation signals were extracted from surface EMG signals. Four modules were sufficient to explain the unperturbed gait and the gait perturbed in any of the perturbation directions. Moreover, three of four modules extracted from the unperturbed gait were the same for gait perturbed forward, leftward, and rightward (similarity in synergies = 0.94 +/- 0.03). On the other hand, the activation signals were different between unperturbed and perturbed gait (average correlation coefficient = 0.55 +/- 0.16). These strategies to recover balance were robust across subjects. In conclusion, changes in lower limb and trunk kinematics provoked by perturbations were reflected in minimal adjustments in the muscular modular organization of walking, with three of four modules preserved from normal walking. Conversely, the activation signals were all substantially influenced by the perturbations, being the result of integration of afferent information and supraspinal control. PMID- 22773785 TI - Nucleotides critical for the interaction of the Streptococcus pyogenes Mga virulence regulator with Mga-regulated promoter sequences. AB - The Mga regulator of Streptococcus pyogenes directly activates the transcription of a core regulon that encodes virulence factors such as M protein (emm), C5a peptidase (scpA), and streptococcal inhibitor of complement (sic) by directly binding to a 45-bp binding site as determined by an electrophoretic mobility shift assay (EMSA) and DNase I protection. However, by comparing the nucleotide sequences of all established Mga binding sites, we found that they exhibit only 13.4% identity with no discernible symmetry. To determine the core nucleotides involved in functional Mga-DNA interactions, the M1T1 Pemm1 binding site was altered and screened for nucleotides important for DNA binding in vitro and for transcriptional activation using a plasmid-based luciferase reporter in vivo. Following this analysis, 34 nucleotides within the Pemm1 binding site that had an effect on Mga binding, Mga-dependent transcriptional activation, or both were identified. Of these critical nucleotides, guanines and cytosines within the major groove were disproportionately identified clustered at the 5' and 3' ends of the binding site and with runs of nonessential adenines between the critical nucleotides. On the basis of these results, a Pemm1 minimal binding site of 35 bp bound Mga at a level comparable to the level of binding of the larger 45-bp site. Comparison of Pemm with directed mutagenesis performed in the M1T1 Mga-regulated PscpA and Psic promoters, as well as methylation interference analysis of PscpA, establish that Mga binds to DNA in a promoter-specific manner. PMID- 22773787 TI - Functional Analysis of Bacillus subtilis Genes Involved in the Biosynthesis of 4 Thiouridine in tRNA. AB - ThiI has been identified as an essential enzyme involved in the biosynthesis of thiamine and the tRNA thionucleoside modification, 4-thiouridine. In Escherichia coli and Salmonella enterica, ThiI acts as a sulfurtransferase, receiving the sulfur donated from the cysteine desulfurase IscS and transferring it to the target molecule or additional sulfur carrier proteins. However, in Bacillus subtilis and most species from the Firmicutes phylum, ThiI lacks the rhodanese domain that contains the site responsible for the sulfurtransferase activity. The lack of the gene encoding for a canonical IscS cysteine desulfurase and the presence of a short sequence of ThiI in these bacteria pointed to mechanistic differences involving sulfur trafficking reactions in both biosynthetic pathways. Here, we have carried out functional analysis of B. subtilis thiI and the adjacent gene, nifZ, encoding for a cysteine desulfurase. Gene inactivation experiments in B. subtilis indicate the requirement of ThiI and NifZ for the biosynthesis of 4-thiouridine, but not thiamine. In vitro synthesis of 4 thiouridine by ThiI and NifZ, along with labeling experiments, suggests the occurrence of an alternate transient site for sulfur transfer, thus obviating the need for a rhodanese domain. In vivo complementation studies in E. coli IscS- or ThiI-deficient strains provide further support for specific interactions between NifZ and ThiI. These results are compatible with the proposal that B. subtilis NifZ and ThiI utilize mechanistically distinct and mutually specific sulfur transfer reactions. PMID- 22773786 TI - TolC-dependent secretion of an ankyrin repeat-containing protein of Rickettsia typhi. AB - Rickettsia typhi, the causative agent of murine (endemic) typhus, is an obligate intracellular pathogen with a life cycle involving both vertebrate and invertebrate hosts. In this study, we characterized a gene (RT0218) encoding a C terminal ankyrin repeat domain-containing protein, named Rickettsia ankyrin repeat protein 1 (RARP-1), and identified it as a secreted effector protein of R. typhi. RT0218 showed differential transcript abundance at various phases of R. typhi intracellular growth. RARP-1 was secreted by R. typhi into the host cytoplasm during in vitro infection of mammalian cells. Transcriptional analysis revealed that RT0218 was cotranscribed with adjacent genes RT0217 (hypothetical protein) and RT0216 (TolC) as a single polycistronic mRNA. Given one of its functions as a facilitator of extracellular protein secretion in some Gram negative bacterial pathogens, we tested the possible role of TolC in the secretion of RARP-1. Using Escherichia coli C600 and an isogenic tolC insertion mutant as surrogate hosts, our data demonstrate that RARP-1 is secreted in a TolC dependent manner. Deletion of either the N-terminal signal peptide or the C terminal ankyrin repeats abolished RARP-1 secretion by wild-type E. coli. Importantly, expression of R. typhi tolC in the E. coli tolC mutant restored the secretion of RARP-1, suggesting that TolC has a role in RARP-1 translocation across the outer membrane. This work implies that the TolC component of the putative type 1 secretion system of R. typhi is involved in the secretion process of RARP-1. PMID- 22773788 TI - Multiple transcription-activating sequences regulate the RsmZ regulatory small RNA of Pseudomonas brassicacearum. AB - The mutS-rpoS region is known to be a highly polymorphic segment of the chromosome owing to horizontal gene transfer and evolutionary processes. In Pseudomonas, mutS-fdxA-rsmZ-rpoS organization is highly conserved, as well as the promoter region of the RsmZ small RNA (sRNA)-encoding gene. One exception to this conservation is in Pseudomonas brassicacearum, where a 308-nucleotide (nt) sequence, predicted to form a hairpin structure in single-stranded DNA (ssDNA), is inserted between the rpoS and rsmZ genes. Using MEME software, we identified nine consensus motifs in the rsmZ promoter region of 16 sequenced Pseudomonas genomes. We observed that an upstream activation sequence (UAS) and an M1 motif (located between the -10 promoter element and the UAS) are shared among examined Pseudomonas genomes. A third motif, the M2 motif, is localized within the coding sequence of the rpoS gene. Constructs fusing the different identified motifs to the lacZ reporter were produced. Our in vivo analysis of the rsmZ-activating elements indicates that the palindromic UAS located 180 bp upstream of the rsmZ transcriptional start in P. brassicacearum NFM 421 is essential, but not sufficient, for full rsmZ expression. Here, we demonstrate a role for the three motifs in the activation of the rsmZ gene, and we hypothesize the role of additional transcriptional factors, along with the DNA structuring role of the hairpin in the complex network controlling the expression of rsmZ. PMID- 22773789 TI - CbrA is a flavin adenine dinucleotide protein that modifies the Escherichia coli outer membrane and confers specific resistance to Colicin M. AB - Colicin M (Cma) is a protein toxin produced by Escherichia coli that kills sensitive E. coli cells by inhibiting murein biosynthesis in the periplasm. Recombinant plasmids carrying cbrA (formerly yidS) strongly increased resistance of cells to Cma, whereas deletion of cbrA increased Cma sensitivity. Transcription of cbrA is positively controlled by the two-component CreBC system. A DeltacreB mutant was highly Cma sensitive because little CbrA was synthesized. Treatment of CbrA-overproducing cells by osmotic shock failed to render cells Cma sensitive because the cells were resistant to osmotic shock. In a natural environment with a growth-limiting nutrient supply, cells producing CbrA defend themselves against colicin M synthesized by competing cells. Isolated CbrA is a protein with noncovalently bound flavin adenine dinucleotide. Sequence comparison and structure prediction assign the closest relative of CbrA with a known crystal structure as digeranylgeranyl-glycerophospholipid reductase of Thermoplasma acidophilum. CbrA is found in Escherichia coli, Citrobacter, and Salmonella bongori but not in other enterobacteria. The next homologs with the highest identity (over 50%) are found in the anaerobic Clostridium botulinum group 1 and a few other Firmicutes. PMID- 22773790 TI - Dual RpoH sigma factors and transcriptional plasticity in a symbiotic bacterium. AB - Sinorhizobium meliloti can live as a soil saprophyte and can engage in a nitrogen fixing symbiosis with plant roots. To succeed in such diverse environments, the bacteria must continually adjust gene expression. Transcriptional plasticity in eubacteria is often mediated by alternative sigma (sigma) factors interacting with core RNA polymerase. The S. meliloti genome encodes 14 of these alternative sigma factors, including two putative RpoH ("heat shock") sigma factors. We used custom Affymetrix symbiosis chips to characterize the global transcriptional response of S. meliloti rpoH1, rpoH2, and rpoH1 rpoH2 mutants during heat shock and stationary-phase growth. Under these conditions, expression of over 300 genes is dependent on rpoH1 and rpoH2. We mapped transcript start sites of 69 rpoH dependent genes using 5' RACE (5' rapid amplification of cDNA ends), which allowed us to determine putative RpoH1-dependent, RpoH2-dependent, and dual promoter (RpoH1- and RpoH2-dependent) consensus sequences that were each used to search the genome for other potential direct targets of RpoH. The inferred S. meliloti RpoH promoter consensus sequences share features of Escherichia coli RpoH promoters but lack extended -10 motifs. PMID- 22773791 TI - Novel listerial glycerol dehydrogenase- and phosphoenolpyruvate-dependent dihydroxyacetone kinase system connected to the pentose phosphate pathway. AB - Several bacteria use glycerol dehydrogenase to transform glycerol into dihydroxyacetone (Dha). Dha is subsequently converted into Dha phosphate (Dha-P) by an ATP- or phosphoenolpyruvate (PEP)-dependent Dha kinase. Listeria innocua possesses two potential PEP-dependent Dha kinases. One is encoded by 3 of the 11 genes forming the glycerol (gol) operon. This operon also contains golD (lin0362), which codes for a new type of Dha-forming NAD(+)-dependent glycerol dehydrogenase. The subsequent metabolism of Dha requires its phosphorylation via the PEP:sugar phosphotransferase system components enzyme I, HPr, and EIIA(Dha)-2 (Lin0369). P~EIIA(Dha)-2 transfers its phosphoryl group to DhaL-2, which phosphorylates Dha bound to DhaK-2. The resulting Dha-P is probably metabolized mainly via the pentose phosphate pathway, because two genes of the gol operon encode proteins resembling transketolases and transaldolases. In addition, purified Lin0363 and Lin0364 exhibit ribose-5-P isomerase (RipB) and triosephosphate isomerase activities, respectively. The latter enzyme converts part of the Dha-P into glyceraldehyde-3-P, which, together with Dha-P, is metabolized via gluconeogenesis to form fructose-6-P. Together with another glyceraldehyde-3-P molecule, the transketolase transforms fructose-6-P into intermediates of the pentose phosphate pathway. The gol operon is preceded by golR, transcribed in the opposite orientation and encoding a DeoR-type repressor. Its inactivation causes the constitutive but glucose-repressible expression of the entire gol operon, including the last gene, encoding a pediocin immunity-like (PedB-like) protein. Its elevated level of synthesis in the golR mutant causes slightly increased immunity against pediocin PA-1 compared to the wild-type strain or a pedB-like deletion mutant. PMID- 22773794 TI - Simplifying guidelines: we only need one adjuvant chemotherapy regimen for breast cancer. PMID- 22773792 TI - Physical interaction between coat morphogenetic proteins SpoVID and CotE is necessary for spore encasement in Bacillus subtilis. AB - Endospore formation by Bacillus subtilis is a complex and dynamic process. One of the major challenges of sporulation is the assembly of a protective, multilayered, proteinaceous spore coat, composed of at least 70 different proteins. Spore coat formation can be divided into two distinct stages. The first is the recruitment of proteins to the spore surface, dependent on the morphogenetic protein SpoIVA. The second step, known as encasement, involves the migration of the coat proteins around the circumference of the spore in successive waves, a process dependent on the morphogenetic protein SpoVID and the transcriptional regulation of individual coat genes. We provide genetic and biochemical evidence supporting the hypothesis that SpoVID promotes encasement of the spore by establishing direct protein-protein interactions with other coat morphogenetic proteins. It was previously demonstrated that SpoVID directly interacts with SpoIVA and the inner coat morphogenetic protein, SafA. Here, we show by yeast two-hybrid and pulldown assays that SpoVID also interacts directly with the outer coat morphogenetic protein, CotE. Furthermore, by mutational analysis, we identified a specific residue in the N-terminal domain of SpoVID that is essential for the interaction with CotE but dispensable for the interaction with SafA. We propose an updated model of coat assembly and spore encasement that incorporates several physical interactions between the principal coat morphogenetic proteins. PMID- 22773793 TI - A Single Amino Acid Substitution Changes the Self-Assembly Status of a Type IV Piliation Secretin. AB - Secretins form large multimeric complexes in the outer membranes of many Gram negative bacteria, where they function as dedicated gateways that allow proteins to access the extracellular environment. Despite their overall relatedness, different secretins use different specific and general mechanisms for their targeting, assembly, and membrane insertion. We report that all tested secretins from several type II secretion systems and from the filamentous bacteriophage f1 can spontaneously multimerize and insert into liposomes in an in vitro transcription-translation system. Phylogenetic analyses indicate that these secretins form a group distinct from the secretins of the type IV piliation and type III secretion systems, which do not autoassemble in vitro. A mutation causing a proline-to-leucine substitution allowed PilQ secretins from two different type IV piliation systems to assemble in vitro, albeit with very low efficiency, suggesting that autoassembly is an inherent property of all secretins. PMID- 22773795 TI - Reaping the benefits of recent advances for adults with acute lymphoblastic leukemia. PMID- 22773796 TI - Ten years of progress in head and neck cancers. PMID- 22773797 TI - Gastric MALT lymphoma treated with primary radiotherapy in the setting of autoimmune disease. AB - Autoimmune and microbial-induced immune reactions are associated with lymphomagenesis, particularly of extranodal marginal zone B-cell lymphomas. This report presents a case of Helicobacter pylori-negative gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the setting of Sjogren syndrome and Hashimoto thyroiditis treated with primary involved-field radiotherapy. This report describes etiologic data, diagnostic and treatment considerations, and sophisticated radiation therapy techniques aimed at reducing long-term toxicity in this indolent disease. PMID- 22773798 TI - Metastatic breast cancer, version 1.2012: featured updates to the NCCN guidelines. AB - These NCCN Guidelines Insights highlight the important updates/changes specific to the management of metastatic breast cancer in the 2012 version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer. These changes/updates include the issue of retesting of biomarkers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2) on recurrent disease, new information regarding first-line combination endocrine therapy for metastatic disease, a new section on monitoring of patients with metastatic disease, and new information on endocrine therapy combined with an mTOR inhibitor as a subsequent therapeutic option. PMID- 22773799 TI - Exocrine pancreas cancer and thromboembolic events: a systematic literature review. AB - Exocrine pancreas cancer continues to represent a significant therapeutic challenge, with high rates of mortality and morbidity, including from thromboembolic events, which have long been described as a frequent complication of the disease. This article provides a systematic and comprehensive review of the literature to address the clinical and pathologic features recognized in pancreas cancer pertaining to thrombosis, and to discuss ongoing investigations of prophylactic anticoagulation in the hopes of improving disease-related outcomes. PMID- 22773800 TI - First-line systemic therapy practice patterns and concordance with NCCN guidelines for patients diagnosed with metastatic NSCLC treated at NCCN institutions. AB - The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) allow many systemic therapy options for patients with metastatic non-small cell lung cancer (NSCLC). This analysis uses the NCCN NSCLC Outcomes Database to report on first line therapy practice patterns and concordance with NCCN Guidelines. The analysis was limited to patients diagnosed with metastatic NSCLC between September 2006 and November 2009 at 1 of 8 participating NCCN Member Institutions. Patient characteristics, regimens used, and guidelines concordance were analyzed. Institutional variation and changes in practice over time were also measured. A total of 1717 patients were included in the analysis. Of these, 1375 (80%) were treated with systemic therapy, most often in the form of a carboplatin-based doublet (51%) or carboplatin-based doublet with targeted therapy (17%). Overall, 76% of patients received care that was concordant with NCCN Guidelines. Among patients with good performance status (n = 167), the most common reasons for not receiving first-line therapy were that therapy was not recommended (39%) or death occurred before treatment (33%). The most common reason for receiving nonconcordant drug therapy was the administration of pemetrexed or erlotinib before its incorporation into the NCCN Guidelines for first-line therapy (53%). Most patients in this cohort received care that was concordant with NCCN Guidelines. The NSCLC Outcomes Database is a valuable resource for evaluating practice patterns and concordance with NCCN Guidelines among patients with NSCLC. PMID- 22773802 TI - The role of the private sector in health care reform. PMID- 22773801 TI - Acute lymphoblastic leukemia. AB - The inaugural NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for acute lymphoblastic leukemia (ALL) were developed as a result of meetings convened by a multi-disciplinary panel of experts in 2011. These NCCN Guidelines provide recommendations on the diagnostic evaluation and workup for ALL, risk assessment, risk-stratified treatment approaches based on the Philadelphia chromosome status and age (adults vs. adolescents/young adults), assessment of minimal residual disease, and supportive care considerations. It is recommended that patients be treated at specialized centers with expertise in the management of ALL. PMID- 22773804 TI - Correspondence. PMID- 22773806 TI - Genetic basis of the "sleeping leaves" revealed. PMID- 22773805 TI - Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation. AB - Topical application of nucleic acids offers many potential therapeutic advantages for suppressing genes in the skin, and potentially for systemic gene delivery. However, the epidermal barrier typically precludes entry of gene-suppressing therapy unless the barrier is disrupted. We now show that spherical nucleic acid nanoparticle conjugates (SNA-NCs), gold cores surrounded by a dense shell of highly oriented, covalently immobilized siRNA, freely penetrate almost 100% of keratinocytes in vitro, mouse skin, and human epidermis within hours after application. Significantly, these structures can be delivered in a commercial moisturizer or phosphate-buffered saline, and do not require barrier disruption or transfection agents, such as liposomes, peptides, or viruses. SNA-NCs targeting epidermal growth factor receptor (EGFR), an important gene for epidermal homeostasis, are > 100-fold more potent and suppress longer than siRNA delivered with commercial lipid agents in cultured keratinocytes. Topical delivery of 1.5 uM EGFR siRNA (50 nM SNA-NCs) for 3 wk to hairless mouse skin almost completely abolishes EGFR expression, suppresses downstream ERK phosphorylation, and reduces epidermal thickness by almost 40%. Similarly, EGFR mRNA in human skin equivalents is reduced by 52% after 60 h of treatment with 25 nM EGFR SNA-NCs. Treated skin shows no clinical or histological evidence of toxicity. No cytokine activation in mouse blood or tissue samples is observed, and after 3 wk of topical skin treatment, the SNA structures are virtually undetectable in internal organs. SNA conjugates may be promising agents for personalized, topically delivered gene therapy of cutaneous tumors, skin inflammation, and dominant negative genetic skin disorders. PMID- 22773807 TI - Phenanthriplatin, a monofunctional DNA-binding platinum anticancer drug candidate with unusual potency and cellular activity profile. AB - Monofunctional platinum(II) complexes of general formula cis-[Pt(NH(3))(2)(N heterocycle)Cl]Cl bind DNA at a single site, inducing little distortion in the double helix. Despite this behavior, these compounds display significant antitumor properties, with a different spectrum of activity than that of classic bifunctional cross-linking agents like cisplatin. To discover the most potent monofunctional platinum(II) compounds, the N-heterocycle was systematically varied to generate a small library of new compounds, with guidance from the X-ray structure of RNA polymerase II (Pol II) stalled at a monofunctional pyriplatin DNA adduct. In pyriplatin, the N-heterocycle is pyridine. The most effective complex evaluated was phenanthriplatin, cis [Pt(NH(3))(2)(phenanthridine)Cl]NO(3), which exhibits significantly greater activity than the Food and Drug Administration-approved drugs cisplatin and oxaliplatin. Studies of phenanthriplatin in the National Cancer Institute 60-cell tumor panel screen revealed a spectrum of activity distinct from that of these clinically validated anticancer agents. The cellular uptake of phenanthriplatin is substantially greater than that of cisplatin and pyriplatin because of the hydrophobicity of the phenanthridine ligand. Phenanthriplatin binds more effectively to 5'-deoxyguanosine monophosphate than to N-acetyl methionine, whereas pyriplatin reacts equally well with both reagents. This chemistry supports DNA as a viable cellular target for phenanthriplatin and suggests that it may avoid cytoplasmic platinum scavengers with sulfur-donor ligands that convey drug resistance. With the use of globally platinated Gaussia luciferase vectors, we determined that phenanthriplatin inhibits transcription in live mammalian cells as effectively as cisplatin, despite its inability to form DNA cross-links. PMID- 22773808 TI - Repetition of Bateman challenges the paradigm. PMID- 22773809 TI - Critical function for the Ras-GTPase activating protein RASA3 in vertebrate erythropoiesis and megakaryopoiesis. AB - Phenotype-driven approaches to gene discovery using inbred mice have been instrumental in identifying genetic determinants of inherited blood dyscrasias. The recessive mutant scat (severe combined anemia and thrombocytopenia) alternates between crisis and remission episodes, indicating an aberrant regulatory feedback mechanism common to erythrocyte and platelet formation. Here, we identify a missense mutation (G125V) in the scat Rasa3 gene, encoding a Ras GTPase activating protein (RasGAP), and elucidate the mechanism producing crisis episodes. The mutation causes mislocalization of RASA3 to the cytosol in scat red cells where it is inactive, leading to increased GTP-bound Ras. Erythropoiesis is severely blocked in scat crisis mice, and ~94% succumb during the second crisis (~30 d of age) from catastrophic hematopoietic failure in the spleen and bone marrow. Megakaryopoiesis is also defective during crisis. Notably, the scat phenotype is recapitulated in zebrafish when rasa3 is silenced. These results highlight a critical, conserved, and nonredundant role for RASA3 in vertebrate hematopoiesis. PMID- 22773811 TI - Heterogeneous networks do not promote cooperation when humans play a Prisoner's Dilemma. AB - It is not fully understood why we cooperate with strangers on a daily basis. In an increasingly global world, where interaction networks and relationships between individuals are becoming more complex, different hypotheses have been put forward to explain the foundations of human cooperation on a large scale and to account for the true motivations that are behind this phenomenon. In this context, population structure has been suggested to foster cooperation in social dilemmas, but theoretical studies of this mechanism have yielded contradictory results so far; additionally, the issue lacks a proper experimental test in large systems. We have performed the largest experiments to date with humans playing a spatial Prisoner's Dilemma on a lattice and a scale-free network (1,229 subjects). We observed that the level of cooperation reached in both networks is the same, comparable with the level of cooperation of smaller networks or unstructured populations. We have also found that subjects respond to the cooperation that they observe in a reciprocal manner, being more likely to cooperate if, in the previous round, many of their neighbors and themselves did so, which implies that humans do not consider neighbors' payoffs when making their decisions in this dilemma but only their actions. Our results, which are in agreement with recent theoretical predictions based on this behavioral rule, suggest that population structure has little relevance as a cooperation promoter or inhibitor among humans. PMID- 22773810 TI - Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. AB - Acquired resistance to EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inevitable in metastatic EGFR-mutant lung cancers. Here, we modeled disease progression using EGFR-mutant human tumor cell lines. Although five of six models displayed alterations already found in humans, one harbored an unexpected secondary NRAS Q61K mutation; resistant cells were sensitive to concurrent EGFR and MEK inhibition but to neither alone. Prompted by this finding and because RAS/RAF/MEK mutations are known mediators of acquired resistance in other solid tumors (colon cancers, gastrointestinal stromal tumors, and melanomas) responsive to targeted therapies, we analyzed the frequency of secondary KRAS/NRAS/BRAF/MEK1 gene mutations in the largest collection to date of lung cancers with acquired resistance to EGFR TKIs. No recurrent NRAS, KRAS, or MEK1 mutations were found in 212, 195, or 146 patient samples, respectively, but 2 of 195 (1%) were found to have mutations in BRAF (G469A and V600E). Ectopic expression of mutant NRAS or BRAF in drug-sensitive EGFR-mutant cells conferred resistance to EGFR TKIs that was overcome by addition of a MEK inhibitor. Collectively, these positive and negative results provide deeper insight into mechanisms of acquired resistance to EGFR TKIs in lung cancer and inform ongoing clinical trials designed to overcome resistance. In the context of emerging knowledge about mechanisms of acquired resistance to targeted therapies in various cancers, our data highlight the notion that, even though solid tumors share common signaling cascades, mediators of acquired resistance must be elucidated for each disease separately in the context of treatment. PMID- 22773812 TI - Efficient and sequence-independent replication of DNA containing a third base pair establishes a functional six-letter genetic alphabet. AB - The natural four-letter genetic alphabet, comprised of just two base pairs (dA-dT and dG-dC), is conserved throughout all life, and its expansion by the development of a third, unnatural base pair has emerged as a central goal of chemical and synthetic biology. We recently developed a class of candidate unnatural base pairs, exemplified by the pair formed between d5SICS and dNaM. Here, we examine the PCR amplification of DNA containing one or more d5SICS-dNaM pairs in a wide variety of sequence contexts. Under standard conditions, we show that this DNA may be amplified with high efficiency and greater than 99.9% fidelity. To more rigorously explore potential sequence effects, we used deep sequencing to characterize a library of templates containing the unnatural base pair as a function of amplification. We found that the unnatural base pair is efficiently replicated with high fidelity in virtually all sequence contexts. The results show that, for PCR and PCR-based applications, d5SICS-dNaM is functionally equivalent to a natural base pair, and when combined with dA-dT and dG-dC, it provides a fully functional six-letter genetic alphabet. PMID- 22773813 TI - Bacterial swimmers that infiltrate and take over the biofilm matrix. AB - Bacteria grow in either planktonic form or as biofilms, which are attached to either inert or biological surfaces. Both growth forms are highly relevant states in nature and of paramount scientific focus. However, interchanges between bacteria in these two states have been little explored. We discovered that a subpopulation of planktonic bacilli is propelled by flagella to tunnel deep within a biofilm structure. Swimmers create transient pores that increase macromolecular transfer within the biofilm. Irrigation of the biofilm by swimmer bacteria may improve biofilm bacterial fitness by increasing nutrient flow in the matrix. However, we show that the opposite may also occur (i.e., swimmers can exacerbate killing of biofilm bacteria by facilitating penetration of toxic substances from the environment). We combined these observations with the fact that numerous bacteria produce antimicrobial substances in nature. We hypothesized and proved that motile bacilli expressing a bactericide can also kill a heterologous biofilm population, Staphylococcus aureus in this case, and then occupy the newly created space. These findings identify microbial motility as a determinant of the biofilm landscape and add motility to the complement of traits contributing to rapid alterations in biofilm populations. PMID- 22773814 TI - Light regulates attachment, exopolysaccharide production, and nodulation in Rhizobium leguminosarum through a LOV-histidine kinase photoreceptor. AB - Rhizobium leguminosarum is a soil bacterium that infects root hairs and induces the formation of nitrogen-fixing nodules on leguminous plants. Light, oxygen, and voltage (LOV)-domain proteins are blue-light receptors found in higher plants and many algae, fungi, and bacteria. The genome of R. leguminosarum bv. viciae 3841, a pea-nodulating endosymbiont, encodes a sensor histidine kinase containing a LOV domain at the N-terminal end (R-LOV-HK). R-LOV-HK has a typical LOV domain absorption spectrum with broad bands in the blue and UV-A regions and shows a truncated photocycle. Here we show that the R-LOV-HK protein regulates attachment to an abiotic surface and production of flagellar proteins and exopolysaccharide in response to light. Also, illumination of bacterial cultures before inoculation of pea roots increases the number of nodules per plant and the number of intranodular bacteroids. The effects of light on nodulation are dependent on a functional lov gene. The results presented in this work suggest that light, sensed by R-LOV-HK, is an important environmental factor that controls adaptive responses and the symbiotic efficiency of R. leguminosarum. PMID- 22773815 TI - TCP transcription factor, BRANCH ANGLE DEFECTIVE 1 (BAD1), is required for normal tassel branch angle formation in maize. AB - In grass inflorescences, a structure called the "pulvinus" is found between the inflorescence main stem and lateral branches. The size of the pulvinus affects the angle of the lateral branches that emerge from the main axis and therefore has a large impact on inflorescence architecture. Through EMS mutagenesis we have identified three complementation groups of recessive mutants in maize having defects in pulvinus formation. All mutants showed extremely acute tassel branch angles accompanied by a significant reduction in the size of the pulvinus compared with normal plants. Two of the complementation groups correspond to mutations in the previously identified genes, RAMOSA2 (RA2) and LIGULELESS1 (LG1). Mutants corresponding to a third group were cloned using mapped-based approaches and found to encode a new member of the plant-specific TCP (TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL NUCLEAR ANTIGEN FACTOR) family of DNA binding proteins, BRANCH ANGLE DEFECTIVE 1 (BAD1). BAD1 is expressed in the developing pulvinus as well as in other developing tissues, including the tassels and juvenile leaves. Both molecular and genetics studies show that RA2 is upstream of BAD1, whereas LG1 may function in a separate pathway. Our findings demonstrate that BAD1 is a TCP class II gene that functions to promote cell proliferation in a lateral organ, the pulvinus, and influences inflorescence architecture by impacting the angle of lateral branch emergence. PMID- 22773816 TI - Mechanism-independent method for predicting response to multidrug combinations in bacteria. AB - Drugs are commonly used in combinations larger than two for treating bacterial infection. However, it is generally impossible to infer directly from the effects of individual drugs the net effect of a multidrug combination. Here we develop a mechanism-independent method for predicting the microbial growth response to combinations of more than two drugs. Performing experiments in both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, we demonstrate that for a wide range of drugs, the bacterial responses to drug pairs are sufficient to infer the effects of larger drug combinations. To experimentally establish the broad applicability of the method, we use drug combinations comprising protein synthesis inhibitors (macrolides, aminoglycosides, tetracyclines, lincosamides, and chloramphenicol), DNA synthesis inhibitors (fluoroquinolones and quinolones), folic acid synthesis inhibitors (sulfonamides and diaminopyrimidines), cell wall synthesis inhibitors, polypeptide antibiotics, preservatives, and analgesics. Moreover, we show that the microbial responses to these drug combinations can be predicted using a simple formula that should be widely applicable in pharmacology. These findings offer a powerful, readily accessible method for the rational design of candidate therapies using combinations of more than two drugs. In addition, the accurate predictions of this framework raise the question of whether the multidrug response in bacteria obeys statistical, rather than chemical, laws for combinations larger than two. PMID- 22773817 TI - A phytochrome-phototropin light signaling complex at the plasma membrane. AB - Phytochromes are red/far-red photochromic photoreceptors central to regulating plant development. Although they are known to enter the nucleus upon light activation and, once there, regulate transcription, this is not the complete picture. Various phytochrome effects are manifested much too rapidly to derive from changes in gene expression, whereas others seem to occur without phytochrome entering the nucleus. Phytochromes also guide directional responses to light, excluding a genetic signaling route and implying instead plasma membrane association and a direct cytoplasmic signal. However, to date, no such association has been demonstrated. Here we report that a phytochrome subpopulation indeed associates physically with another photoreceptor, phototropin, at the plasma membrane. Yeast two-hybrid methods using functional photoreceptor molecules showed that the phytochrome steering growth direction in Physcomitrella protonemata binds several phototropins specifically in the photoactivated Pfr state. Split-YFP studies in planta showed that the interaction occurs exclusively at the plasma membrane. Coimmunoprecipitation experiments provided independent confirmation of in vivo phy-phot binding. Consistent with this interaction being associated with a cellular signal, we found that phytochrome-mediated tropic responses are impaired in Physcomitrella phot(-) mutants. Split-YFP revealed a similar interaction between Arabidopsis phytochrome A and phototropin 1 at the plasma membrane. These associations additionally provide a functional explanation for the evolution of neochrome photoreceptors. Our results imply that the elusive phytochrome cytoplasmic signal arises through binding and coaction with phototropin at the plasma membrane. PMID- 22773818 TI - Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice. AB - Tim-1, a type I transmembrane glycoprotein, consists of an IgV domain and a mucin domain. The IgV domain is essential for binding Tim-1 to its ligands, but little is known about the role of the mucin domain, even though genetic association of TIM-1 with atopy/asthma has been linked to the length of mucin domain. We generated a Tim-1-mutant mouse (Tim-1(Deltamucin)) in which the mucin domain was deleted genetically. The mutant mice showed a profound defect in IL-10 production from regulatory B cells (Bregs). Associated with the loss of IL-10 production in B cells, older Tim-1(Deltamucin) mice developed spontaneous autoimmunity associated with hyperactive T cells, with increased production of IFN-gamma and elevated serum levels of Ig and autoantibodies. However, Tim-1(Deltamucin) mice did not develop frank systemic autoimmune disease unless they were crossed onto the Fas-mutant lpr mice on a C57BL/6 background. Tim-1(Deltamucin)lpr mice developed accelerated and fulminant systemic autoimmunity with accumulation of abnormal double-negative T cells and autoantibodies to a number of lupus associated autoantigens. Thus, Tim-1 plays a critical role in maintaining suppressive Breg function, and our data also demonstrate an unexpected role of the Tim-1 mucin domain in regulating Breg function and maintaining self tolerance. PMID- 22773819 TI - beta-Arrestin2 mediates the initiation and progression of myeloid leukemia. AB - beta-Arrestins were initially discovered as negative regulators of G protein coupled receptor signaling. Although beta-arrestins have more recently been implicated as scaffold proteins that interact with various mitogenic and developmental signals, the genetic role of beta-arrestins in driving oncogenesis is not known. Here we have investigated the role of beta-arrestin in hematologic malignancies and have found that although both beta-arrestin1 and -2 are expressed in the hematopoietic system, loss of beta-arrestin2 preferentially leads to a severe impairment in the establishment and propagation of the chronic and blast crisis phases of chronic myelogenous leukemia (CML). These defects are linked to a reduced frequency, as well as defective self-renewal capacity of the cancer stem-cell population, in mouse models and in human CML patient samples. At a molecular level, the loss of beta-arrestin2 leads to a significant inhibition of beta-catenin stabilization, and ectopic activation of Wnt signaling reverses the defects observed in the beta-arrestin2 mutant cells. These data cumulatively show that beta-arrestin2 is essential for CML disease propagation and indicate that beta-arrestins and the Wnt/beta-catenin pathway lie in a signaling hierarchy in the context of CML cancer stem cell maintenance. PMID- 22773821 TI - Does specialty training prepare doctors for senior roles? A questionnaire study of new UK consultants. AB - AIM: To measure new consultants' perceptions of their preparedness for different clinical and non-clinical aspects of the role of consultant. DESIGN: A cross specialty questionnaire was developed and validated, containing items asking how well specialty training had prepared respondents for the role of consultant in a number of clinical and non-clinical areas. Responses were on a five-point Likert scale with a 'Not relevant/no opinion' box, and one free text section. Analysis was carried out on 10 scales derived from the questionnaire items through exploratory factor analysis. PARTICIPANTS: Consultants who had completed their specialty training in the north of England between 2004 and 2009 and had held a substantive consultant post in the region for <5 years were sent questionnaires in late 2009. RESULTS: The effective response rate was 70.6% (211/299). Ten factors reflecting areas including clinical skills, communication skills, team and resource management were identified. Overall, higher scores were observed on factors relating to 'providing care for individual patients' rather than 'having responsibility for the system of care'. The lowest scoring factors related to resource management and supervision, with mean scores falling below the scale midpoint. There were no significant differences between specialty groups, or on any demographic variables. CONCLUSIONS: A questionnaire to measure new consultants' perceptions of how well their specialty training had prepared them for practice was developed and validated. Findings were similar across specialties, suggesting that training programmes in all areas need to integrate higher-level management skills into their curricula, alongside the development of clinical expertise. PMID- 22773822 TI - Initiation of adjuvant hormone therapy by Medicaid insured women with nonmetastatic breast cancer. AB - Hormone therapy is the mainstay of adjuvant treatment for hormone receptor positive (HR-positive) nonmetastatic breast cancer. We evaluated adjuvant hormone therapy (AHT) initiation among Medicaid-insured women aged 21-64 years with stage I-III HR-positive breast cancer. We used multivariable logistic regression to identify independent predictors of AHT initiation. Within 1 year of diagnosis, 68% (1049/1538) initiated AHT; by 18 months, 80% (1168/1461) initiated AHT. In multivariable analysis, women less likely to initiate AHT had more comorbidity (>= 2 vs none: adjusted odds ratio (AOR) = 0.55; 95% CI = 0.32 to 0.97), more advanced disease (stage III vs I: AOR = 0.27; 95% CI = 0.18 to 0.39), and no radiation after breast conserving surgery (AOR = 0.15; 95% CI = 0.10 to 0.22). Race, age, and history of mental health disorders were not independently associated with initiation of AHT. Among initiators of AHT, 58% (604/1049) were adherent to treatment for the year after initiation. Despite comprehensive prescription coverage, only 39% (604/1538) received optimal AHT including prompt initiation and adherence for the year after treatment. Partnerships between Medicaid programs and cancer registries may help identify at-risk women and facilitate the implementation of quality improvement strategies. PMID- 22773820 TI - HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120. AB - HIV-1 envelope glycoprotein is the primary target for HIV-1-specific antibodies. The native HIV-1 envelope spike on the virion surface is a trimer, but trimeric gp140 and monomeric gp120 currently are believed to induce comparable immune responses. Indeed, most studies on the immunogenicity of HIV-1 envelope oligomers have revealed only marginal improvement over monomers. We report here that suitably prepared envelope trimers have nearly all the antigenic properties expected for native viral spikes. These stable, rigorously homogenous trimers have antigenic properties markedly different from those of monomeric gp120s derived from the same sequences, and they induce potent neutralizing antibody responses for a cross-clade set of tier 1 and tier 2 viruses with titers substantially higher than those elicited by the corresponding gp120 monomers. These results, which demonstrate that there are relevant immunologic differences between monomers and high-quality envelope trimers, have important implications for HIV-1 vaccine development. PMID- 22773824 TI - Breast cancer risk after use of fertility drugs: stimulating new controversy. PMID- 22773825 TI - Fertility drugs and young-onset breast cancer: results from the Two Sister Study. AB - BACKGROUND: Fertility drugs stimulate hyperovulation, which may have implications for breast cancer. We examined the association between use of fertility drugs (clomiphene citrate [CC] and follicle-stimulating hormone [FSH]) and subsequent risk of young-onset (<50 years at diagnosis) breast cancer. METHODS: We conducted the Two Sister Study, a sister-matched case-control study, by enrolling 1422 women between September 2008 and December 2010, who were younger than age 50 years at diagnosis with breast cancer and were enrolled within 4 years of diagnosis, and 1669 breast cancer-free control sisters from the Sister Study. Participants reported their use of fertility drugs (CC and FSH) and ever-users reported whether a pregnancy had resulted that lasted 10 or more (10+) weeks. Conditional logistic regression was used to estimate confounder-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for fertility drug use with or without conception of a 10+ week pregnancy. RESULTS: A total of 288 participants reported having used ovulation-stimulating drugs (193 CC only, 29 FSH only, and 66 both). Overall, women who had used fertility drugs showed a non-statistically significantly decreased risk of breast cancer, compared with nonusers (OR = 0.82, 95% CI = 0.63 to 1.08). Women who had used fertility drugs but had not conceived a 10+ week pregnancy under treatment showed a statistically significantly decreased risk of breast cancer compared with nonusers (OR = 0.62, 95% CI = 0.43 to 0.89). Women who had used fertility drugs and conceived a 10+ week pregnancy under treatment showed a statistically significantly increased risk of breast cancer compared with unsuccessfully treated women (OR = 1.82, 95% CI = 1.10 to 3.00), although their risk was not increased compared with women who had not used fertility drugs (OR = 1.13, 95% CI = 0.78 to 1.64). CONCLUSIONS: In the absence of a 10+ week pregnancy under treatment, exposure to ovulation-stimulating fertility drugs was associated with reduced risk of young-onset breast cancer. This apparent association was absent in women who conceived a 10+ week pregnancy under treatment, for whom risk was higher than that of unsuccessfully treated women, but similar to that of untreated women. PMID- 22773826 TI - Age-specific incidence of breast cancer subtypes: understanding the black-white crossover. AB - BACKGROUND: Breast cancer incidence is higher among black women than white women before age 40 years, but higher among white women than black women after age 40 years (black-white crossover). We used newly available population-based data to examine whether the age-specific incidences of breast cancer subtypes vary by race and ethnicity. METHODS: We classified 91908 invasive breast cancers diagnosed in California between January 1, 2006, and December 31, 2009, by subtype based on tumor expression of estrogen receptor (ER) and progesterone receptor (PR)-together referred to as hormone receptor (HR)-and human epidermal growth factor receptor 2 (HER2). Breast cancer subtypes were classified as ER or PR positive and HER2 negative (HR(+)/HER2(-)), ER or PR positive and HER2 positive (HR(+)/HER2(+)), ER and PR negative and HER2 positive (HR(-)/HER2(+)), and ER, PR, and HER2 negative (triple-negative). We calculated and compared age specific incidence rates, incidence rate ratios, and 95% confidence intervals by subtype and race (black, white, Hispanic, and Asian). All P values are two-sided. RESULTS: We did not observe an age-related black-white crossover in incidence for any molecular subtype of breast cancer. Compared with white women, black women had statistically significantly higher rates of triple-negative breast cancer at all ages but statistically significantly lower rates of HR(+)/HER2(-) breast cancers after age 35 years (all P < .05). The age-specific incidence of HR(+)/HER2(+) and HR(-)/HER2(+) subtypes did not vary markedly between white and black women. CONCLUSIONS: The black-white crossover in breast cancer incidence occurs only when all breast cancer subtypes are combined and relates largely to higher rates of triple-negative breast cancers and lower rates of HR(+)/HER2(-) breast cancers in black vs white women. PMID- 22773827 TI - Growth-dependent podocyte failure causes glomerulosclerosis. AB - Podocyte depletion leads to glomerulosclerosis, but whether an impaired capacity of podocytes to respond to hypertrophic stress also causes glomerulosclerosis is unknown. We generated transgenic Fischer 344 rats that express a dominant negative AA-4E-BP1 transgene driven by the podocin promoter; a member of the mammalian target of rapamycin complex 1 (mTORC1) pathway, 4E-BP1 modulates cap dependent translation, which is a key determinant of a cell's hypertrophic response to nutrients and growth factors. AA-4E-BP1 rat podocytes expressed the transgene and had normal kidney histology and protein excretion at 100 g of body weight but developed ESRD by 12 months. Proteinuria and glomerulosclerosis were linearly related to both increasing body weight and transgene dose. Uni nephrectomy reduced the body weight at which proteinuria first developed by 40% 50%. The initial histologic manifestation of disease was the appearance of bare areas of glomerular basement membrane from the pulling apart of podocyte foot processes, followed by adhesions to the Bowman capsule. Morphometric analysis confirmed the mismatch between glomerular tuft volume and total podocyte volume (number * size) per tuft in relation to weight gain and nephrectomy. Proteinuria and glomerulosclerosis did not develop if dietary calorie restriction prevented weight gain and glomerular enlargement. In summary, failure of podocytes to match glomerular tuft growth in response to growth signaling through the mTORC1 pathway can trigger proteinuria, glomerulosclerosis, and progression to ESRD. Reducing body weight and glomerular growth may be useful adjunctive therapies to slow or prevent progression to ESRD. PMID- 22773828 TI - alpha-Galactosidase aggregation is a determinant of pharmacological chaperone efficacy on Fabry disease mutants. AB - Fabry disease is a lysosomal storage disorder caused by loss of alpha galactosidase function. More than 500 Fabry disease mutants have been identified, the majority of which are structurally destabilized. A therapeutic strategy under development for lysosomal storage diseases consists of using pharmacological chaperones to stabilize the structure of the mutant protein, thereby promoting lysosomal delivery over retrograde degradation. The substrate analog 1 deoxygalactonojirimycin (DGJ) has been shown to restore activity of mutant alpha galactosidase and is currently in clinical trial for treatment of Fabry disease. However, only ~65% of tested mutants respond to treatment in cultured patient fibroblasts, and the structural underpinnings of DGJ response remain poorly explained. Using computational modeling and cell culture experiments, we show that the DGJ response is negatively affected by protein aggregation of alpha galactosidase mutants, revealing a qualitative difference between misfolding associated and aggregation-associated loss of function. A scoring function combining predicted thermodynamic stability and intrinsic aggregation propensity of mutants captures well their aggregation behavior under overexpression in HeLa cells. Interestingly, the same classifier performs well on DGJ response data of patient-derived cultured lymphoblasts, showing that protein aggregation is an important determinant of chemical chaperone efficiency under endogenous expression levels as well. Our observations reinforce the idea that treatment of aggregation-associated loss of function observed for the more severe alpha galactosidase mutants could be enhanced by combining pharmacological chaperone treatment with the suppression of mutant aggregation, e.g. via proteostatic regulator compounds that increase cellular chaperone expression. PMID- 22773829 TI - Glucocorticoid receptor activation inhibits p53-induced apoptosis of MCF10Amyc cells via induction of protein kinase Cepsilon. AB - Glucocorticoid receptor (GR) is a ligand-dependent transcription factor that can promote apoptosis or survival in a cell-specific manner. Activated GR has been reported to inhibit apoptosis in mammary epithelial cells and breast cancer cells by increasing pro-survival gene expression. In this study, activated GR inhibited p53-dependent apoptosis in MCF10A cells and human mammary epithelial cells that overexpress the MYC oncogene. Specifically, GR agonists hydrocortisone or dexamethasone inhibited p53-dependent apoptosis induced by cisplatin, ionizing radiation, or the MDM2 antagonist Nutlin-3. In contrast, the GR antagonist RU486 sensitized the cells to apoptosis by these agents. Apoptosis inhibition was associated with maintenance of mitochondrial membrane potential, diminished caspase-3 and -7 activation, and increased expression at both the mRNA and protein level of the anti-apoptotic PKC family member PKCepsilon. Knockdown of PKCepsilon via siRNA targeting reversed the protective effect of dexamethasone and restored apoptosis sensitivity. These data provide evidence that activated GR can inhibit p53-dependent apoptosis through induction of the anti-apoptotic factor PKCepsilon. PMID- 22773830 TI - Protein disulfide isomerase is required for platelet-derived growth factor induced vascular smooth muscle cell migration, Nox1 NADPH oxidase expression, and RhoGTPase activation. AB - Vascular Smooth Muscle Cell (VSMC) migration into vessel neointima is a therapeutic target for atherosclerosis and postinjury restenosis. Nox1 NADPH oxidase-derived oxidants synergize with growth factors to support VSMC migration. We previously described the interaction between NADPH oxidases and the endoplasmic reticulum redox chaperone protein disulfide isomerase (PDI) in many cell types. However, physiological implications, as well as mechanisms of such association, are yet unclear. We show here that platelet-derived growth factor (PDGF) promoted subcellular redistribution of PDI concomitant to Nox1-dependent reactive oxygen species production and that siRNA-mediated PDI silencing inhibited such reactive oxygen species production, while nearly totally suppressing the increase in Nox1 expression, with no change in Nox4. Furthermore, PDI silencing inhibited PDGF-induced VSMC migration assessed by distinct methods, whereas PDI overexpression increased spontaneous basal VSMC migration. To address possible mechanisms of PDI effects, we searched for PDI interactome by systems biology analysis of physical protein-protein interaction networks, which indicated convergence with small GTPases and their regulator RhoGDI. PDI silencing decreased PDGF-induced Rac1 and RhoA activities, without changing their expression. PDI co-immunoprecipitated with RhoGDI at base line, whereas such association was decreased after PDGF. Also, PDI co-immunoprecipitated with Rac1 and RhoA in a PDGF-independent way and displayed detectable spots of perinuclear co-localization with Rac1 and RhoGDI. Moreover, PDI silencing promoted strong cytoskeletal changes: disorganization of stress fibers, decreased number of focal adhesions, and reduced number of RhoGDI-containing vesicular recycling adhesion structures. Overall, these data suggest that PDI is required to support Nox1/redox and GTPase-dependent VSMC migration. PMID- 22773831 TI - Profilin1 regulates sternum development and endochondral bone formation. AB - Bone development is a dynamic process that requires cell motility and morphological adaptation under the control of actin cytoskeleton. This actin cytoskeleton system is regulated by critical modulators including actin-binding proteins. Among them, profilin1 (Pfn1) is a key player to control actin fiber structure, and it is involved in a number of cellular activities such as migration. During the early phase of body development, skeletal stem cells and osteoblastic progenitor cells migrate to form initial rudiments for future skeletons. During this migration, these cells extend their process based on actin cytoskeletal rearrangement to locate themselves in an appropriate location within microenvironment. However, the role of Pfn1 in regulation of mesenchymal progenitor cells (MPCs) during skeletal development is incompletely understood. Here we examined the role of Pfn1 in skeletal development using a genetic ablation of Pfn1 in MPCs by using Prx1-Cre recombinase. We found that Pfn1 deficiency in MPCs caused complete cleft sternum. Notably, Pfn1-deficient mice exhibited an absence of trabecular bone in the marrow space of appendicular long bone. This phenotype is location-specific, as Pfn1 deficiency did not largely affect osteoblasts in cortical bone. Pfn1 deficiency also suppressed longitudinal growth of long bone. In vitro, Pfn1 deficiency induced retardation of osteoblastic cell migration. These observations revealed that Pfn1 is a critical molecule for the skeletal development, and this could be at least in part associated with the retardation of cell migration. PMID- 22773832 TI - Induction of specific microRNAs inhibits cutaneous wound healing. AB - Chronic nonhealing wounds, such as venous ulcers (VUs), are a widespread and serious medical problem with high morbidity and mortality. The molecular pathology of VUs remains poorly understood, impeding the development of effective treatment strategies. Using mRNA expression profiling of VUs biopsies and computational analysis, we identified a candidate set of microRNAs with lowered target gene expression. Among these candidates, miR-16, -20a, -21, -106a -130a, and -203 were confirmed to be aberrantly overexpressed in a cohort study of 10 VU patients by quantitative PCR and in situ hybridizations. These microRNAs were predicted to target multiple genes important for wound healing, including early growth response factor 3, vinculin, and leptin receptor (LepR). Overexpression of the top up-regulated miRNAs, miR-21 and miR-130a, in primary human keratinocytes down-regulated expression of the endogenous LepR and early growth response factor 3. The luciferase reporter assay verified LepR as a direct target for miR-21 and miR-130a. Both miR-21 and miR-130a delayed epithelialization in an acute human skin wound model. Furthermore, in vivo overexpression of miR-21 inhibited epithelialization and granulation tissue formation in a rat wound model. Our results identify a novel mechanism in which overexpression of specific set of microRNAs inhibits wound healing, resulting in new potential molecular markers and targets for therapeutic intervention. PMID- 22773833 TI - Diindolylmethane-mediated Gli1 protein suppression induces anoikis in ovarian cancer cells in vitro and blocks tumor formation ability in vivo. AB - Anoikis is a cell death that occurs due to detachment of a cell from the extracellular matrix (ECM). Resistance to anoikis is a primary feature of a cell that undergoes metastasis. In this study for the first time, we demonstrated the potential role of Gli1 in anoikis resistance. Treatment of various ovarian cancer cells by different concentrations of diindolylmethane (DIM), an active ingredient of cruciferous vegetables, reduced the anoikis resistance in a concentration dependent manner. Reduction in anoikis resistance was associated with a decrease in the expression of Gli1 and an increase in the cleavage of poly(ADP-ribose) polymerase (PARP). Sonic hedgehog (Shh) treatment not only increased the expression of Gli1, but also blocked anoikis induced by DIM and abrogated the change in the expression of Gli1 and cleaved PARP by DIM. To confirm the role of Gli1, hedgehog inhibitor cyclopamine, Gli1 siRNA and Gli1(-/-) mouse embryonic fibroblasts (MEFs) were used. Cyclopamine treatment alone significantly reduced anoikis resistance in A2780 and OVCAR-429 cells. Cyclopamine-mediated reduction in anoikis resistance was associated with reduced expression of Gli1 and induction of cleaved PARP. Shh treatment blocked cyclopamine-induced anoikis. Silencing Gli1 expression induced anoikis and cleavage of PARP in A2780 and OVCAR 429 cells. Furthermore, Gli1(-/-) MEFs were more sensitive to anoikis compared with Gli1(+/+) MEFs. Our in vivo studies established that DIM- or cyclopamine treated ovarian cancer cells under suspension culture conditions drastically lost their ability of tumor formation in vivo in mice. Taken together, our results establish that Gli1 is a critical player in anoikis resistance in ovarian cancer. PMID- 22773834 TI - Chemoenzymatic synthesis of heparin oligosaccharides with both anti-factor Xa and anti-factor IIa activities. AB - Heparan sulfate (HS) and heparin are highly sulfated polysaccharides. Heparin is a commonly used anticoagulant drug that inhibits the activities of factors Xa and IIa (also known as thrombin) to prevent blood clot formation. Here, we report the synthesis of a series of size-defined oligosaccharides to probe the minimum size requirement for an oligosaccharide with anti-IIa activity. The synthesis was completed by a chemoenzymatic approach involving glycosyltransferases, HS sulfotransferases, and C(5)-epimerase. We demonstrate the ability to synthesize highly purified N-sulfo-oligosaccharides having up to 21 saccharide residues. The results from anti-Xa and anti-IIa activity measurements revealed that an oligosaccharide longer than 19 saccharide residues is necessary to display anti IIa activity. The oligosaccharides also exhibit low binding toward platelet factor 4, raising the possibility of preparing a synthetic heparin with a reduced effect of heparin-induced thrombocytopenia. The results from this study demonstrate the ability to synthesize large HS oligosaccharides and provide a unique tool to probe the structure and function relationships of HS that require the use of large HS fragments. PMID- 22773835 TI - TRAF family member-associated NF-kappaB activator (TANK) is a negative regulator of osteoclastogenesis and bone formation. AB - The differentiation of bone-resorbing osteoclasts is induced by RANKL signaling, and leads to the activation of NF-kappaB via TRAF6 activation. TRAF family member associated NF-kappaB activator (TANK) acts as a negative regulator of Toll-like receptors (TLRs) and B-cell receptor (BCR) signaling by inhibiting TRAF6 activation. Tank(-/-) mice spontaneously develop autoimmune glomerular nephritis in an IL-6-dependent manner. Despite its importance in the TCRs and BCR-activated TRAF6 inhibition, the involvement of TANK in RANKL signaling is poorly understood. Here, we report that TANK is a negative regulator of osteoclast differentiation. The expression levels of TANK mRNA and protein were up-regulated during RANKL-induced osteoclastogenesis, and overexpression of TANK in vitro led to a decrease in osteoclast formation. The in vitro osteoclastogenesis of Tank(-/ ) cells was significantly increased, accompanied by increased ubiquitination of TRAF6 and enhanced canonical NF-kappaB activation in response to RANKL stimulation. Tank(-/-) mice showed severe trabecular bone loss, but increased cortical bone mineral density, because of enhanced bone erosion and formation. TANK mRNA expression was induced during osteoblast differentiation and Tank(-/-) osteoblasts exhibited enhaced NF-kappaB activation, IL-11 expression, and bone nodule formation than wild-type control cells. Finally, wild-type mice transplanted with bone marrow cells from Tank(-/-) mice showed trabecular bone loss analogous to that in Tank(-/-) mice. These findings demonstrate that TANK is critical for osteoclastogenesis by regulating NF-kappaB, and is also important for proper bone remodeling. PMID- 22773837 TI - Constitutive dimerization of glycoprotein VI (GPVI) in resting platelets is essential for binding to collagen and activation in flowing blood. AB - The platelet collagen receptor glycoprotein VI (GPVI) has been suggested to function as a dimer, with increased affinity for collagen. Dissociation constants (K(d)) obtained by measuring recombinant GPVI binding to collagenous substrates showed that GPVI dimers bind with high affinity to tandem GPO (Gly-Pro-Hyp) sequences in collagen, whereas the markedly lower affinity of the monomer for all substrates implies that it is not the collagen-binding form of GPVI. Dimer binding required a high density of immobilized triple-helical (GPO)(10) containing peptide, suggesting that the dimer binds multiple, discrete peptide helices. Differential inhibition of dimer binding by dimer-specific antibodies, m Fab-F and 204-11 Fab, suggests that m-Fab-F binds at the collagen-binding site of the dimer, and 204-11 Fab binds to a discrete site. Flow cytometric quantitation indicated that GPVI dimers account for ~29% of total GPVI in resting platelets, whereas activation by either collagen-related peptide or thrombin increases the number of dimers to ~39 and ~44%, respectively. m-Fab-F inhibits both GPVI dependent static platelet adhesion to collagen and thrombus formation on collagen under low and high shear, indicating that pre-existing dimeric GPVI is required for the initial interaction with collagen because affinity of the monomer is too low to support binding and that interaction through the dimer is essential for platelet activation. These GPVI dimers in resting circulating platelets will enable them to bind injury-exposed subendothelial collagen to initiate platelet activation. The GPVI-specific agonist collagen-related peptide or thrombin further increases the number of dimers, thereby providing a feedback mechanism for reinforcing binding to collagen and platelet activation. PMID- 22773838 TI - Elongation factor G is a critical target during oxidative damage to the translation system of Escherichia coli. AB - Elongation factor G (EF-G), a key protein in translational elongation, is known to be particularly susceptible to oxidation in Escherichia coli. However, neither the mechanism of the oxidation of EF-G nor the influence of its oxidation on translation is fully understood. In the present study, we investigated the effects of oxidants on the chemical properties and function of EF-G using a translation system in vitro derived from E. coli. Treatment of EF-G with 0.5 mM H(2)O(2) resulted in the complete loss of translational activity. The inactivation of EF-G by H(2)O(2) was attributable to the oxidation of two specific cysteine residues, namely, Cys(114) and Cys(266), and subsequent formation of an intramolecular disulfide bond. Replacement of Cys(114) by serine rendered EF-G insensitive to oxidation and inactivation by H(2)O(2). Furthermore, generation of the translation system in vitro with the mutated EF-G protected the entire translation system from oxidation, suggesting that EF-G might be a primary target of oxidation within the translation system. Oxidized EF-G was reactivated via reduction of the disulfide bond by thioredoxin, a ubiquitous protein that mediates dithiol-disulfide exchange. Our observations indicate that the translational machinery in E. coli is regulated, in part, by the redox state of EF-G, which might depend on the balance between the supply of reducing power and the degree of oxidative stress. PMID- 22773836 TI - Angiotensin-II and MARCKS: a hydrogen peroxide- and RAC1-dependent signaling pathway in vascular endothelium. AB - MARCKS is an actin-binding protein that modulates vascular endothelial cell migration and cytoskeleton signaling (Kalwa, H., and Michel, T. (2011) J. Biol. Chem. 286, 2320-2330). Angiotensin-II is a vasoactive peptide implicated in vascular physiology as well as pathophysiology; the pathways connecting angiotensin-II and cytoskeletal remodeling are incompletely understood. Here we show that MARCKS is expressed in intact arterial preparations, with prominent staining of the endothelium. In endothelial cells, angiotensin-II-promoted MARCKS phosphorylation is abrogated by PEG-catalase, implicating endogenous H(2)O(2) in the angiotensin-II response. Studies using the H(2)O(2) biosensor HyPer2 reveal that angiotensin-II promotes increases in intracellular H(2)O(2). We used a Rac1 FRET biosensor to show that angiotensin-II promotes Rac1 activation that is attenuated by PEG-catalase. siRNA-mediated Rac1 knockdown blocks angiotensin-II stimulated MARCKS phosphorylation. Cell imaging studies using a phosphoinositide 4,5-bisphosphate (PIP(2)) biosensor revealed that angiotensin-II PIP(2) regulation depends on MARCKS and H(2)O(2). siRNA-mediated knockdown of MARCKS or Rac1 attenuates receptor-mediated activation of the tyrosine kinase c-Abl and disrupts actin fiber formation. These studies establish a critical role for H(2)O(2) in angiotensin-II signaling to the endothelial cytoskeleton in a novel pathway that is critically dependent on MARCKS, Rac1, and c-Abl. PMID- 22773839 TI - Protein kinase Calpha (PKCalpha) regulates p53 localization and melanoma cell survival downstream of integrin alphav in three-dimensional collagen and in vivo. AB - Protein kinase C alpha (PKCalpha) is overexpressed in numerous types of cancer. Importantly, PKCalpha has been linked to metastasis of malignant melanoma in patients. However, it has been unclear how PKCalpha may be regulated and how it exerts its role in melanoma. Here, we identified a role for PKCalpha in melanoma cell survival in a three-dimensional collagen model mimicking the in vivo pathophysiology of the dermis. A pathway was identified that involved integrin alphav-mediated up-regulation of PKCalpha and PKCalpha-dependent regulation of p53 localization, which was connected to melanoma cell survival. Melanoma survival and growth in three-dimensional microenvironments requires the expression of integrin alphav, which acts to suppress p53 activity. Interestingly, microarray analysis revealed that PKCalpha was up-regulated by integrin alphav in a three-dimensional microenvironment-dependent manner. Integrin alphav was observed to promote a relocalization of endogenous p53 from the nucleus to the cytoplasm upon growth in three-dimensional collagen as well as in vivo, whereas stable knockdown of PKCalpha inhibited the integrin alphav mediated relocalization of p53. Importantly, knockdown of PKCalpha also promoted apoptosis in three-dimensional collagen and in vivo, resulting in reduced tumor growth. This indicates that PKCalpha constitutes a crucial component of the integrin alphav-mediated pathway(s) that promote p53 relocalization and melanoma survival. PMID- 22773840 TI - Inhibition of pokeweed antiviral protein (PAP) by turnip mosaic virus genome linked protein (VPg). AB - Pokeweed antiviral protein (PAP) from Phytolacca americana is a ribosome inactivating protein (RIP) and an RNA N-glycosidase that removes specific purine residues from the sarcin/ricin loop of large rRNA, arresting protein synthesis at the translocation step. PAP is also a cap-binding protein and is a potent antiviral agent against many plant, animal, and human viruses. To elucidate the mechanism of RNA depurination, and to understand how PAP recognizes and targets various RNAs, the interactions between PAP and turnip mosaic virus genome-linked protein (VPg) were investigated. VPg can function as a cap analog in cap independent translation and potentially target PAP to uncapped IRES-containing RNA. In this work, fluorescence spectroscopy and HPLC techniques were used to quantitatively describe PAP depurination activity and PAP-VPg interactions. PAP binds to VPg with high affinity (29.5 nm); the reaction is enthalpically driven and entropically favored. Further, VPg is a potent inhibitor of PAP depurination of RNA in wheat germ lysate and competes with structured RNA derived from tobacco etch virus for PAP binding. VPg may confer an evolutionary advantage by suppressing one of the plant defense mechanisms and also suggests the possible use of this protein against the cytotoxic activity of ribosome-inactivating proteins. PMID- 22773841 TI - Calmodulin-binding locations on the skeletal and cardiac ryanodine receptors. AB - Ryanodine receptor types 1 (RyR1) and 2 (RyR2) are calcium release channels that are highly enriched in skeletal and cardiac muscle, respectively, where they play an essential role in excitation-contraction coupling. Apocalmodulin (apo-CaM) weakly activates RyR1 but inhibits RyR2, whereas Ca(2+)-calmodulin inhibits both isoforms. Previous cryo-EM studies showed distinctly different binding locations on RyR1 for the two states of CaM. However, recent studies employing FRET appear to challenge these findings. Here, using cryo-EM, we have determined that a CaM mutant that is incapable of binding calcium binds to RyR1 at the apo site, regardless of the calcium concentration. We have also re-determined the location of RyR1-bound Ca(2+)-CaM using uniform experimental conditions. Our results show the existence of the two overlapping but distinct binding sites for CaM in RyR1 and imply that the binding location switch is due to Ca(2+) binding to CaM, as opposed to direct effects of Ca(2+) on RyR1. We also discuss explanations that could resolve the apparent conflict between the cryo-EM and FRET results. Interestingly, apo-CaM binds to RyR2 at a similar binding location to that of Ca(2+)-CaM on RyR1, in seeming agreement with the inhibitory effects of these two forms of CaM on their respective receptors. PMID- 22773842 TI - Design of bioactive peptides from naturally occurring MU-conotoxin structures. AB - To date, cone snail toxins ("conotoxins") are of great interest in the pursuit of novel subtype-selective modulators of voltage-gated sodium channels (Na(v)s). Na(v)s participate in a wide range of electrophysiological processes. Consequently, their malfunctioning has been associated with numerous diseases. The development of subtype-selective modulators of Na(v)s remains highly important in the treatment of such disorders. In current research, a series of novel, synthetic, and bioactive compounds were designed based on two naturally occurring MU-conotoxins that target Na(v)s. The initial designed peptide contains solely 13 amino acids and was therefore named "Mini peptide." It was derived from the MU-conotoxins KIIIA and BuIIIC. Based on this Mini peptide, 10 analogues were subsequently developed, comprising 12-16 amino acids with two disulfide bridges. Following appropriate folding and mass verification, blocking effects on Na(v)s were investigated. The most promising compound established an IC(50) of 34.1 +/- 0.01 nM (R2-Midi on Na(v)1.2). An NMR structure of one of our most promising compounds was determined. Surprisingly, this structure does not reveal an alpha helix. We prove that it is possible to design small peptides based on known pharmacophores of MU-conotoxins without losing their potency and selectivity. These data can provide crucial material for further development of conotoxin based therapeutics. PMID- 22773844 TI - Annexin-1-mediated endothelial cell migration and angiogenesis are regulated by vascular endothelial growth factor (VEGF)-induced inhibition of miR-196a expression. AB - Endothelial cell migration induced in response to vascular endothelial growth factor (VEGF) is an essential step of angiogenesis. It depends in part on the activation of the p38/MAPKAP kinase-2/LIMK1/annexin-A1 (ANXA1) signaling axis. In the present study, we obtained evidence indicating that miR-196a specifically binds to the 3'-UTR region of ANXA1 mRNA to repress its expression. In accordance with the role of ANXA1 in cell migration and angiogenesis, the ectopic expression of miR-196a is associated with decreased cell migration in wound closure assays, and the inhibitory effect of miR-196a is rescued by overexpressing ANXA1. This finding highlights the fact that ANXA1 is a required mediator of VEGF-induced cell migration. miR-196a also reduces the formation of lamellipodia in response to VEGF suggesting that ANXA1 regulates cell migration by securing the formation of lamellipodia at the leading edge of the cell. Additionally, in line with the fact that cell migration is an essential step of angiogenesis, the ectopic expression of miR-196a impairs the formation of capillary-like structures in a tissue-engineered model of angiogenesis. Here again, the effect of miR-196a is rescued by overexpressing ANXA1. Moreover, the presence of miR-196a impairs the VEGF-induced in vivo neo-vascularization in the Matrigel Plug assay. Interestingly, VEGF reduces the expression of miR-196a, which is associated with an increased level of ANXA1. Similarly, the inhibition of miR-196a with an antagomir results in an increased level of ANXA1. We conclude that the VEGF induced decrease of miR-196a expression may participate to the angiogenic switch by maintaining the expression of ANXA1 to levels required to enable p38-ANXA1 dependent endothelial cell migration and angiogenesis in response to VEGF. PMID- 22773843 TI - The Wnt receptor Ryk plays a role in mammalian planar cell polarity signaling. AB - Wnts are essential for a wide range of developmental processes, including cell growth, division, and differentiation. Some of these processes signal via the planar cell polarity (PCP) pathway, which is a beta-catenin-independent Wnt signaling pathway. Previous studies have shown that Ryk, a member of the receptor tyrosine kinase family, can bind to Wnts. Ryk is required for normal axon guidance and neuronal differentiation during development. Here, we demonstrate that mammalian Ryk interacts with the Wnt/PCP pathway. In vitro analysis showed that the Wnt inhibitory factor domain of Ryk was necessary for Wnt binding. Detailed analysis of two vertebrate model organisms showed Ryk phenotypes consistent with PCP signaling. In zebrafish, gene knockdown using morpholinos revealed a genetic interaction between Ryk and Wnt11 during the PCP pathway regulated process of embryo convergent extension. Ryk-deficient mouse embryos displayed disrupted polarity of stereociliary hair cells in the cochlea, a characteristic of disturbed PCP signaling. This PCP defect was also observed in mouse embryos that were double heterozygotes for Ryk and Looptail (containing a mutation in the core Wnt/PCP pathway gene Vangl2) but not in either of the single heterozygotes, suggesting a genetic interaction between Ryk and Vangl2. Co immunoprecipitation studies demonstrated that RYK and VANGL2 proteins form a complex, whereas RYK also activated RhoA, a downstream effector of PCP signaling. Overall, our data suggest an important role for Ryk in Wnt/planar cell polarity signaling during vertebrate development via the Vangl2 signaling pathway, as demonstrated in the mouse cochlea. PMID- 22773846 TI - Dogs imitate selectively, not necessarily rationally: reply to. AB - ? We address the authors' criticisms of Range et al. (2007, Curr Biol, 17, 1-5). ? We point at unfavourable methodological differences between the two studies. ? Most critical is a substantial difference in the dogs' baseline performance. ? Priming cannot account for the selective imitation effect. ? We are therefore not surprised that the "replication" failed. PMID- 22773845 TI - The mechanism of pre-transfer editing in yeast mitochondrial threonyl-tRNA synthetase. AB - Accurate translation of mRNA into protein is a fundamental biological process critical for maintaining normal cellular functions. To ensure translational fidelity, aminoacyl-tRNA synthetases (aaRSs) employ pre-transfer and post transfer editing activities to hydrolyze misactivated and mischarged amino acids, respectively. Whereas post-transfer editing, which requires either a specialized domain in aaRS or a trans-protein factor, is well described, the mechanism of pre transfer editing is less understood. Here, we show that yeast mitochondrial threonyl-tRNA synthetase (MST1), which lacks an editing domain, utilizes pre transfer editing to discriminate against serine. MST1 misactivates serine and edits seryl adenylate (Ser-AMP) in a tRNA-independent manner. MST1 hydrolyzes 80% of misactivated Ser-AMP at a rate 4-fold higher than that for the cognate threonyl adenylate (Thr-AMP) while releasing 20% of Ser-AMP into the solution. To understand the mechanism of pre-transfer editing, we solved the crystal structure of MST1 complexed with an analog of Ser-AMP. The binding of the Ser-AMP analog to MST1 induces conformational changes in the aminoacylation active site, and it positions a potential hydrolytic water molecule more favorably for nucleophilic attack. In addition, inhibition results reveal that the Ser-AMP analog binds the active site 100-fold less tightly than the Thr-AMP analog. In conclusion, we propose that the plasticity of the aminoacylation site in MST1 allows binding of Ser-AMP and the appropriate positioning of the hydrolytic water molecule. PMID- 22773847 TI - Synthesis and Characterization of New Trinuclear Copper Complexes. AB - This report describes our approach towards modelling the copper cluster active sites of nitrous oxide reductase and the multicopper oxidases/oxygenases. We have synthesized two mesitylene-based trinucleating ligands, MesPY1 and MesPY2, which employ bis(2-picolyl)amine (PY1) and bis(2-pyridylethyl)amine (PY2) tridentate copper chelates, respectively. Addition of cuprous salts to these ligands leads to the isolation of tricopper(I) complexes [(Mes-PY1)Cu(I) (3)(CH(3)CN)(3)](ClO(4))(3).0.25Et(2)O (1) and [(Mes-PY2)Cu(I) (3)](PF(6))(3) (3) Each of the three copper centers in 1 is most likely four-coordinate, with ligated acetonitrile as the fourth ligand; by contrast, the copper centers in 3 are three-coordinate, as determined by X-ray crystallography The synthesis of [(Mes-PY1)Cu(II) (3)(CH(3)CN)(2)(CH(3)OH)(2)](ClO(4))(6).(CH(3)OH) (2) was accomplished by addition of three equivalents of the copper(II) salt, Cu(ClO(4))(2).6H(2)O, to the ligand. The structure of 2 shows that two of the copper centers are tetracoordinate (with MeCN solvent ligation), but have additional weak axial (fifth ligand) interactions with the perchlorate anions; the third copper is unique in that it is coordinated by two MeOH solvent molecules, making it overall five-coordinate. For complexes 2 and 3, one copper ion center is located on the opposite side of the mesitylene plane as the other two. These observations, although in the solid state, must be taken into account for future studies where intramolecular tricopper(I)/O(2) (or other small molecules of interest) interactions in solution are desirable. PMID- 22773848 TI - Strategies for assessing proton linkage to bimolecular interactions by global analysis of isothermal titration calorimetry data. AB - Isothermal titration calorimetry (ITC) is a traditional and powerful method for studying the linkage of ligand binding to proton uptake or release. The theoretical framework has been developed for more than two decades and numerous applications have appeared. In the current work, we explored strategic aspects of experimental design. To this end, we simulated families of ITC data sets that embed different strategies with regard to the number of experiments, range of experimental pH, buffer ionization enthalpy, and temperature. We then re-analyzed the families of data sets in the context of global analysis, employing a proton linkage binding model implemented in the global data analysis platform SEDPHAT, and examined the information content of all data sets by a detailed statistical error analysis of the parameter estimates. In particular, we studied the impact of different assumptions about the knowledge of the exact concentrations of the components, which in practice presents an experimental limitation for many systems. For example, the uncertainty in concentration may reflect imperfectly known extinction coefficients and stock concentrations or may account for different extents of partial inactivation when working with proteins at different pH values. Our results show that the global analysis can yield reliable estimates of the thermodynamic parameters for intrinsic binding and protonation, and that in the context of the global analysis the exact molecular component concentrations may not be required. Additionally, a comparison of data from different experimental strategies illustrates the benefit of conducting experiments at a range of temperatures. PMID- 22773849 TI - A Robust and Efficient Method for Steady State Patterns in Reaction-Diffusion Systems. AB - An inhomogeneous steady state pattern of nonlinear reaction-diffusion equations with no-flux boundary conditions is usually computed by solving the corresponding time-dependent reaction-diffusion equations using temporal schemes. Nonlinear solvers (e.g., Newton's method) take less CPU time in direct computation for the steady state; however, their convergence is sensitive to the initial guess, often leading to divergence or convergence to spatially homogeneous solution. Systematically numerical exploration of spatial patterns of reaction-diffusion equations under different parameter regimes requires that the numerical method be efficient and robust to initial condition or initial guess, with better likelihood of convergence to an inhomogeneous pattern. Here, a new approach that combines the advantages of temporal schemes in robustness and Newton's method in fast convergence in solving steady states of reaction-diffusion equations is proposed. In particular, an adaptive implicit Euler with inexact solver (AIIE) method is found to be much more efficient than temporal schemes and more robust in convergence than typical nonlinear solvers (e.g., Newton's method) in finding the inhomogeneous pattern. Application of this new approach to two reaction diffusion equations in one, two, and three spatial dimensions, along with direct comparisons to several other existing methods, demonstrates that AIIE is a more desirable method for searching inhomogeneous spatial patterns of reaction diffusion equations in a large parameter space. PMID- 22773850 TI - Value From Adversity: How We Deal With Adversity Matters. AB - Participants in our study worked on an anagram task to win a prize while aversive noise played in the background. They were instructed to deal with the noise either by "opposing" it as an interference or by "coping" with the unpleasant feelings it created. The strength of attention to the opposing or coping response to adversity was measured by poorer recognition of the content of the background noise. For the "opposing" participants, it was predicted that the more they attended to opposing the interference, they stronger they would engage in solving the anagrams to win the prize, which would increase the prize's value. For the "coping" participants, it was predicted that the more they attended to coping with their unpleasant feelings, the weaker they would engage in solving the anagrams to win the prize, which would decrease the prize's value. The results supported both predictions. PMID- 22773851 TI - Neurological picture. Transient high-intensity signal of heterotopia on DWI in an epilepsy patient. PMID- 22773852 TI - Neurological picture. Acquired hepatocerebral degeneration revealed by neurogenic hyperventilation syndrome and myelitis. PMID- 22773853 TI - Classification of familial amyotrophic lateral sclerosis by family history: effects on frequency of genes mutation. AB - OBJECTIVE: To classify familial amyotrophic lateral sclerosis (FALS) on the base of family history, and to determine whether frequency of mutations in major amyotrophic lateral sclerosis (ALS) genes varies in different FALS categories. METHODS: Included in the study are 53 FALS families. Patients were classified as definite, probable and possible FALS, according to recently proposed criteria. Seven ALS-associated genes, including SOD1, TARDBP, FUS, ANG, ATXN2, OPTN and C9ORF72, were analysed. RESULTS: Thirteen patients (24.5%) were included in the definite group. The great majority of our FALS cases (40/53, 75.5%) were families with only two affected relatives; of these, 31 (58.5%) were included in the probable, and 9 (17%) in the possible FALS categories. The percentage of mutations was 61.5% in definite, 41.9% in probable and 11.1% in possible FALS. With respect to probable FALS, if cases with parent-to-child transmission of the disease were considered separately, the mutational load increased to 61.5%, as observed in definite FALS. CONCLUSIONS: Our findings provide evidence that frequency of mutations in currently known ALS genes varies widely among different FALS categories. Families with only two affected relatives have heterogeneous genetic components, the chance to detect mutations being higher in cases with parent-to-child transmission. PMID- 22773854 TI - Neuropsychological outcome after selective amygdalohippocampectomy: subtemporal versus transsylvian approach. AB - OBJECTIVE: In the context of discussions on the optimal cognitive outcome of temporal lobe epilepsy surgery, and stimulated by recent reports on the beneficial effects of a selective subtemporal approach to memory function, this study evaluated the cognitive consequences of subtemporal versus transsylvian selective amygdalohippocampectomy (SAH) in patients with mesial temporal lobe epilepsy, taking verbal/figural memory and language functions into account. METHODS: We contrasted cognitive outcomes of 26 subtemporal SAH patients with those observed in a transsylvian SAH control group. The surgical groups were pairwise matched with regard to clinical and demographic characteristics. Preoperative and 1 year postoperative memory and language evaluations served as within group factors, and surgical approach (transsylvian vs subtemporal) and side of surgery (right vs left) as between group factors. RESULTS: Both surgical approaches caused decline in verbal memory to a similar degree. Differential effects were seen with regard to decline in verbal recognition memory (more affected by left transsylvian SAH) as well as in figural memory and verbal fluency (more affected by subtemporal SAH). INTERPRETATION: Different from previous optimistic reports, this study demonstrates that subtemporal surgery, such as transsylvian surgery, poses similar risks for verbal memory. Differences between the approaches appear to reflect the effect of different collateral temporal lobe lesions due to the approach. Different cognitive outcomes across studies on the subtemporal approach are discussed as being in part due to study design and the chosen dependent functional measures. PMID- 22773856 TI - Adult-onset spinocerebellar ataxia due to MTATP6 mutations: are they more common than previously thought? PMID- 22773855 TI - Risk and outcomes for traumatic brain injury in patients with mental disorders. AB - OBJECTIVE: To investigate the risk of traumatic brain injury (TBI) and post injury mortality in patients with mental disorders. BACKGROUND: Patients with mental disorders are at higher risk of injuries. However, the association between mental disorders and TBI is still not understood. We conducted case-control studies to investigate whether people with pre-existing mental disorders are at higher risk of TBI and post-injury mortality. METHODS: Using reimbursement claims, we analysed 16,635 patients with TBI and 66,540 controls with adjustment of covariates to study the association of mental disorders and TBI. A nested case control study was also conducted to analyse contributory factors for post-injury mortality. RESULTS: People with mental disorders were at increased risk of TBI (odds ratio (OR) 1.94, 95% confidence interval (CI) 1.86 to 2.02). Men, older age, living in highly urbanised areas and patients on low income had a higher risk of TBI and post-injury mortality. Psychiatric medication intensity and frequency of psychiatric visits was significantly correlated with TBI in a severity dependent relationship (p for trend <0.0001). Patients receiving advanced psychiatric healthcare had an increased risk of TBI (OR 2.98, 95% CI 2.67 to 3.33) and post-injury mortality (OR 1.92, 95% CI 1.34 to 2.77). A history of receiving psychiatric related outpatient care (OR 1.77, 95% CI 1.70 to 1.85), hospitalisation (OR 3.21, 95% CI 2.79 to 3.70) or emergency visits (OR 3.53, 95% CI 3.15 to 3.94) were highly associated with subsequent TBI. CONCLUSIONS: Patients with mental disorders have an increased risk of TBI. Intensity of psychiatric medication is associated with increased post-injury mortality. Special attention to prevent TBI among this disabled population is mandatory. PMID- 22773857 TI - Phenotypes and genetic architecture of focal primary torsion dystonia. AB - BACKGROUND: The focal primary torsion dystonias (FPTDs) form a group of clinical heterogeneous syndromes and can be considered a genetic complex disease; it is thought to be primed by genetic variants with variable impact and triggered by non-genetic factors. Thorough clinical description of FPTDs cohorts is sparse but essential for further progress in genetic research. OBJECTIVE: To establish suggested relations between age at onset (AaO), site and family history in a large focal dystonias cohort and gain more insight into familial clustering for genetic research. PATIENTS AND METHODS: A prospective cohort study between March 2008 and March 2011, including 676 FPTD patients attending the botulinum toxin outpatient clinics of six Dutch movement disorder centres. RESULTS AND CONCLUSIONS: Of all of the FPTD patients, 25% had a familial predisposition; in 2.4% a Mendelian inheritance pattern was noted. With a stronger family history, a significantly lower AaO was seen in all focal dystonias. In both the sporadic and familial focal dystonia groups, AaO had an effect on the distribution of dystonia, with a caudal to cranial tendency. In all focal dystonia forms, women were more frequently affected, except for writer's cramp. Careful clinical characterisation will allow the formation of phenotype subgroups. We suggest that genetic research into FPTDs will benefit from this approach and discuss genetic research strategies to decipher the complex background of focal dystonias. PMID- 22773858 TI - Neurological picture. Sub-acute hydrocephalus in a patient with influenza A (H3N2) virus-related cerebellitis. PMID- 22773860 TI - Neurological picture. Nitrous oxide-induced myelopathy with inverted V-sign on spinal MRI. PMID- 22773859 TI - Imaging gait disorders in parkinsonism: a review. AB - Gait difficulties--including freezing of gait--are frequent and disabling symptoms of advanced Parkinson's disease and other parkinsonian syndromes. They respond poorly to current medical and surgical treatments, making patient management very difficult. The underlying pathophysiology remains largely unknown. The late onset of levodopa resistance of Parkinson's disease gait abnormalities has been suggested to result from the progressive extension of the degenerative process to non-dopaminergic structures involved in locomotion, such as cortico-frontal and brainstem networks. Deficiencies in other neurotransmission systems, involving acetylcholine, serotonin or norepinephrine, have also been evoked. Neuroimaging tools appear well suited to decipher the cerebral substrates of parkinsonian gait disorders and their modulation by dopaminergic medication or deep brain stimulation. Here the main functional and metabolic neuroimaging studies aimed at identifying these cerebral networks are reviewed, in both healthy subjects and parkinsonian patients. After a brief overview of the physiology and pathophysiology of gait control, the methodology, main results and limits of the studies published to date are examined. The most promising methods to examine gait difficulties and their response to currently available treatments are then discussed. PMID- 22773861 TI - Computational Optogenetics: A Novel Continuum Framework for the Photoelectrochemistry of Living Systems. AB - Electrical stimulation is currently the gold standard treatment for heart rhythm disorders. However, electrical pacing is associated with technical limitations and unavoidable potential complications. Recent developments now enable the stimulation of mammalian cells with light using a novel technology known as optogenetics. The optical stimulation of genetically engineered cells has significantly changed our understanding of electrically excitable tissues, paving the way towards controlling heart rhythm disorders by means of photostimulation. Controlling these disorders, in turn, restores coordinated force generation to avoid sudden cardiac death. Here, we report a novel continuum framework for the photoelectrochemistry of living systems that allows us to decipher the mechanisms by which this technology regulates the electrical and mechanical function of the heart. Using a modular multiscale approach, we introduce a non-selective cation channel, channelrhodopsin-2, into a conventional cardiac muscle cell model via an additional photocurrent governed by a light-sensitive gating variable. Upon optical stimulation, this channel opens and allows sodium ions to enter the cell, inducing electrical activation. In side-by-side comparisons with conventional heart muscle cells, we show that photostimulation directly increases the sodium concentration, which indirectly decreases the potassium concentration in the cell, while all other characteristics of the cell remain virtually unchanged. We integrate our model cells into a continuum model for excitable tissue using a nonlinear parabolic second order partial differential equation, which we discretize in time using finite differences and in space using finite elements. To illustrate the potential of this computational model, we virtually inject our photosensitive cells into different locations of a human heart, and explore its activation sequences upon photostimulation. Our computational optogenetics tool box allows us to virtually probe landscapes of process parameters, and to identify optimal photostimulation sequences with the goal to pace human hearts with light and, ultimately, to restore mechanical function. PMID- 22773862 TI - Synthesis of Functionalized 4-Methylenetetrahydropyrans by Oxidative Activation of Cinnamyl or Benzyl Ethers. AB - Oxidative activation of benzyl or cinnamyl ether bearing allylsilane derivatives using a catalytic amount of DDQ and 2 equivalents of CAN in the presence of PPTS provided functionalized 4-methylenetetrahydropyrans in good yields and excellent diastereoselectivity. The reaction could be applied to the synthesis of a variety of substituted tetrahydropyran derivatives. PMID- 22773864 TI - Bromination at C-5 of Pyrimidine and C-8 of Purine Nucleosides with 1,3-Dibromo 5,5-dimethylhydantoin. AB - Treatment of the protected and unprotected nucleosides with 1,3-dibromo-5,5- dimethylhydantoin in aprotic solvents such as CH(2)Cl(2), CH(3)CN, or DMF effected smooth bromination of uridine and cytidine derivatives at C-5 of pyrimidine rings as well as adenosine and guanosine derivatives at C-8 of purine rings. Addition of Lewis acids such as trimethylsilyl trifluoromethanesulfonate enhanced efficiency of bromination. PMID- 22773863 TI - Inhibiting glycogen synthase kinase-3 decreases 12-O-tetradecanoylphorbol-13 acetate-induced interferon-gamma-mediated skin inflammation. AB - Glycogen synthase kinase-3 (GSK-3) facilitates interferon (IFN)-gamma signaling. Because IFN-gamma is involved in inflammatory skin diseases, such as psoriasis, the aim of this study was to investigate the pathogenic role of GSK-3 in 12-O tetradecanoylphorbol-13-acetate (TPA)-induced IFN-gamma-mediated ear skin inflammation. TPA (3 MUg per ear) induced acute skin inflammation in the ears of C57BL/6 mice, including edema, infiltration of granulocytes but not T cells, and IFN-gamma receptor 1-mediated deregulation of intercellular adhesion molecule 1 (CD54). TPA/IFN-gamma induced GSK-3 activation, which in turn activated signal transducer and activator of transcription 1. Inhibiting GSK-3 pharmacologically, by administering 6-bromoindirubin-3'-oxime (1.5 MUg per ear), and genetically, with lentiviral-based short-hairpin RNA, reduced TPA-induced acute skin inflammation but not T-cell infiltration. It is noteworthy that inhibiting GSK-3 decreased TPA-induced IFN-gamma production and the nuclear translocation of T-box transcription factor Tbx21, a transcription factor of IFN-gamma, in CD3-positive T cells. In chronic TPA-induced skin inflammation, inhibiting GSK-3 attenuated epidermis hyperproliferation and dermis angiogenesis. These results demonstrate the dual role of GSK-3 in TPA-induced skin inflammation that is not only to facilitate IFN-gamma signaling but also to regulate IFN-gamma production. Inhibiting GSK-3 may be a potential treatment strategy for preventing such effects. PMID- 22773866 TI - Parenthood and host resistance to the common cold. AB - OBJECTIVE: To determine whether parenthood predicts host resistance to the common cold among healthy volunteers experimentally exposed to a common cold virus. METHODS: Participants were 795 healthy volunteers (age range = 18-55 years) enrolled in one of three viral-challenge studies conducted from 1993 to 2004. After reporting parenthood status, participants were quarantined, administered nasal drops containing one of four common cold viruses, and monitored for the development of a clinical cold (infection in the presence of objective signs of illness) on the day before and for 5 to 6 days after exposure. All analyses included controls for immunity to the experimental virus (prechallenge specific antibody titers), viral strain, season, age, sex, race/ethnicity, marital status, body mass, study, employment status, and education. RESULTS: Parents were less likely to develop colds than nonparents were (odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.31-0.73). This was true for both parents with one to two children (OR = 0.52, 95% CI = 0.33-0.83) and three or more children (OR = 0.39, 95% CI = 0.22-0.70). Parenthood was associated with a decreased risk of colds for both those with at least one child living at home (OR = 0.46, 95% CI = 0.24-0.87) and those whose children all lived away from home (OR = 0.27, 95% CI = 0.12-0.60). The relationship between parenthood and colds was not observed in parents aged 18 to 24 years but was pronounced among older parents. CONCLUSIONS: Parenthood was associated with greater host resistance to common cold viruses. PMID- 22773867 TI - Personality and Substance Use in Midlife: Conscientiousness as a Moderator and the Effects of Trait Change. AB - Personality traits predict substance use in adolescence, but less is known about prospective substance use in middle age and beyond. Moreover, there is growing interest in how personality change and the multiplicative effects among personality traits relate to substance use. Participants included approximately 4,000 adults aged 25-74 who participated in two waves of the Midlife in the U.S. (MIDUS) study. Higher levels of neuroticism, extraversion, openness, and lower levels of conscientiousness and agreeableness predicted longitudinal substance use. Increases in neuroticism and openness predicted increased substance use while increases in conscientiousness and agreeableness predicted decreased substance use. Higher levels of conscientiousness moderated two of the other trait main effects. Personality, trait change, and interactions among traits reliably forecasted 10-year substance-use behaviors. PMID- 22773868 TI - Bridging planning and execution: Temporal planning of syllables. AB - This study compares the time to initiate words with varying syllable structures (V, VC, CV, CVC, CCV, CCVC). In order to test the hypothesis that different syllable structures require different amounts of time to prepare their temporal controls, or plans, two delayed naming experiments were carried out. In the first of these the initiation time was determined from acoustic recordings. The results confirmed the hypothesis but also showed an interaction with the initial segment (i.e., vowel-initial words were initiated later than words beginning with consonants, but this difference was much smaller for words starting stops compared to /l/ or /s/). Adding a coda did not affect the initiation time. In order to rule out effects of segment-specific articulatory to acoustic interval differences, a second experiment was performed in which speech movements of the tongue, the jaw and the lips were recorded by means of electromagnetic articulography. Results from initiation time, based on articulatory measurements, showed a significant syllable structure effect with VC words being initiated significantly later than CV(C) words. Only minor effects of the initial segment were found. These results can be partly explained by the amount of accumulated experience a speaker has in coordinating the relevant gesture combinations and triggering them appropriately in time. PMID- 22773869 TI - Identification of Breast Cancer Prognosis Markers via Integrative Analysis. AB - In breast cancer research, it is of great interest to identify genomic markers associated with prognosis. Multiple gene profiling studies have been conducted for such a purpose. Genomic markers identified from the analysis of single datasets often do not have satisfactory reproducibility. Among the multiple possible reasons, the most important one is the small sample sizes of individual studies. A cost-effective solution is to pool data from multiple comparable studies and conduct integrative analysis. In this study, we collect four breast cancer prognosis studies with gene expression measurements. We describe the relationship between prognosis and gene expressions using the accelerated failure time (AFT) models. We adopt a 2-norm group bridge penalization approach for marker identification. This integrative analysis approach can effectively identify markers with consistent effects across multiple datasets and naturally accommodate the heterogeneity among studies. Statistical and simulation studies demonstrate satisfactory performance of this approach. Breast cancer prognosis markers identified using this approach have sound biological implications and satisfactory prediction performance. PMID- 22773870 TI - Physiological and Welfare Consequences of Transport, Relocation, and Acclimatization of Chimpanzees (Pan troglodytes). AB - Manipulations of the environments of captive nonhuman primates often have welfare consequences to the animals, including behavioral effects, and for certain manipulations, physiological effects as well. The processes of transporting, relocating, and acclimatizing nonhuman primates across facilities represent manipulations that are likely to have welfare, behavioral, and physiological consequences to the relocated animals. Seventy-two chimpanzees were relocated from the Primate Foundation of Arizona (PFA) in Arizona to the Keeling Center (KCCMR) in Texas. Animals were transported for approximately 21 h in single cages in a USDA-approved, climate-controlled trailer. Chimpanzees were weighed, anesthetized, and blood samples were collected 1) immediately prior to departure from PFA, 2) immediately upon arrival at the KCCMR, and 3) at additional time point(s) between 3 and 12 weeks after arrival at the KCCMR. Chimpanzees were quarantined in familiar pairs or social groups for 60-90 days at the KCCMR. Blood samples were analyzed for hematological and clinical chemistry parameters and compared across time points. In addition, samples from a subset of animals were assayed for cell-mediated immune parameters. Comparisons of the data obtained just prior to transport, to the data obtained immediately upon arrival, revealed numerous statistically significant differences in hematological, clinical chemistry, and immunological parameters. Some of these were indicative of stress, and thus, changes in welfare state, although many remained within the published normal ranges for chimpanzees. Additional analyses showed that many of the clinical chemistry values collected 3 to 12 weeks after arrival at the KCCMR had returned to pre-transport values. In contrast, of the cell-mediated immune parameters that were affected by transport and relocation, few had returned to pre-transport levels 8 weeks after transport, and three of the four hematology variables analyzed had not returned to pre-transport levels 12 weeks after transport. Comparisons of body weights before and immediately after transport revealed that animals lost an average of 2.5 kg during the 21-h transport, a statistically significant reduction that some animals never regained. These results demonstrate that transport and relocation affect a variety of physiological parameters with potential welfare implications and that some of these effects last as long as 3 months. These findings have important implications for the welfare and use of recently transported nonhuman primates, especially chimpanzees, in biomedical research. In order to allow animals to adapt to their new surroundings and to prevent unwanted confounds from influencing experiments, sufficient time must be provided after transport for chimpanzees to acclimatize. PMID- 22773872 TI - Academic Performance of Subsequent Schools and Impacts of Early Interventions: Evidence from a Randomized Controlled Trial in Head Start Settings. AB - The role of subsequent school contexts in the long-term effects of early childhood interventions has received increasing attention, but has been understudied in the literature. Using data from the Chicago School Readiness Project (CSRP), a cluster-randomized controlled trial conducted in Head Start programs, we investigate whether the intervention had differential effects on academic and behavioral outcomes in kindergarten if children attended high- or low-performing schools subsequent to the preschool intervention year. To address the issue of selection bias, we adopt an innovative method, principal score matching, and control for a set of child, mother, and classroom covariates. We find that exposure to the CSRP intervention in the Head Start year had significant effects on academic and behavioral outcomes in kindergarten for children who subsequently attended high-performing schools, but no significant effects on children attending low-performing schools. Policy implications of the findings are discussed. PMID- 22773871 TI - When zebras become painted donkeys: Grammatical gender and semantic priming interact during picture integration in a spoken Spanish sentence. AB - This study investigates the contribution of grammatical gender to integrating depicted nouns into sentences during on-line comprehension, and whether semantic congruity and gender agreement interact using two tasks: naming and semantic judgement of pictures. Native Spanish speakers comprehended spoken Spanish sentences with an embedded line drawing, which replaced a noun that either made sense or not with the preceding sentence context and either matched or mismatched the gender of the preceding article. In Experiment 1a (picture naming) slower naming times were found for gender mismatching pictures than matches, as well as for semantically incongruous pictures than congruous ones. In addition, the effects of gender agreement and semantic congruity interacted; specifically, pictures that were both semantically incongruous and gender mismatching were named slowest, but not as slow as if adding independent delays from both violations. Compared with a neutral baseline, with pictures embedded in simple command sentences like "Now please say ____", both facilitative and inhibitory effects were observed. Experiment 1b replicated these results with low-cloze gender-neutral sentences, more similar in structure and processing demands to the experimental sentences. In Experiment 2, participants judged a picture's semantic fit within a sentence by button-press; gender agreement and semantic congruity again interacted, with gender agreement having an effect on congruous but not incongruous pictures. Two distinct effects of gender are hypothesised: a "global" predictive effect (observed with and without overt noun production), and a "local" inhibitory effect (observed only with production of gender-discordant nouns). PMID- 22773873 TI - Assessment of anti-recombination and double-strand break-induced gene conversion in human cells by a chromosomal reporter. AB - Gene conversion is one of the frequent end results of homologous recombination, and it often underlies the inactivation of tumor suppressor genes in cancer cells. Here, we have developed an integrated assay system that allows simultaneous examination of double-strand break (DSB)-induced gene conversion events at the site of a DSB (proximal region) and at a surrounding region ~1 kb away from the break (distal region). Utilizing this assay system, we find that gene conversion events at the proximal and distal regions are relatively independent of one another. The results also indicate that synthesis-dependent strand annealing (SDSA) plays a major role in DSB-induced gene conversion. In addition, our current study has demonstrated that hMLH1 plays an essential role in anti-recombination and gene conversion. Specifically, the anti-recombination activity of hMLH1 is partially dependent on its interaction with hMRE11. Our data suggests that the role of hMLH1 and hMRE11 in the process of gene conversion is complex, and these proteins play different roles in DSB-induced proximal and distal gene conversions. In particular, the involvement of hMLH1 and hMRE11 in the distal gene conversion requires both hMSH2 and heteroduplex formation. PMID- 22773875 TI - Contribution of the C-terminal regions of promyelocytic leukemia protein (PML) isoforms II and V to PML nuclear body formation. AB - Promyelocytic leukemia protein (PML) nuclear bodies are dynamic and heterogeneous nuclear protein complexes implicated in various important functions, most notably tumor suppression. PML is the structural component of PML nuclear bodies and has several nuclear splice isoforms that share a common N-terminal region but differ in their C termini. Previous studies have suggested that the coiled-coil motif within the N-terminal region is sufficient for PML nuclear body formation by mediating homo/multi-dimerization of PML molecules. However, it has not been investigated whether any of the C-terminal variants of PML may contribute to PML body assembly. Here we report that the unique C-terminal domains of PML-II and PML-V can target to PML-NBs independent of their N-terminal region. Strikingly, both domains can form nuclear bodies in the absence of endogenous PML. The C terminal domain of PML-II interacts transiently with unknown binding sites at PML nuclear bodies, whereas the C-terminal domain of PML-V exhibits hyperstable binding to PML bodies via homo-dimerization. This strong interaction is mediated by a putative alpha-helix in the C terminus of PML-V. Moreover, nuclear bodies assembled from the C-terminal domain of PML-V also recruit additional PML body components, including Daxx and Sp100. These observations establish the C-terminal domain of PML-V as an additional important contributor to the assembly mechanism(s) of PML bodies. PMID- 22773874 TI - Oxidation of dihydrotestosterone by human cytochromes P450 19A1 and 3A4. AB - Dihydrotestosterone is a more potent androgen than testosterone and plays an important role in endocrine function. We demonstrated that, like testosterone, dihydrotestosterone can be oxidized by human cytochrome P450 (P450) 19A1, the steroid aromatase. The products identified include the 19-hydroxy- and 19-oxo derivatives and the resulting Delta(1,10)-, Delta(5,10)-, and Delta(9,10)-dehydro 19-norsteroid products (loss of 19-methyl group). The overall catalytic efficiency of oxidation was ~10-fold higher than reported for 3alpha-reduction by 3alpha-hydroxysteroid dehydrogenase, the major enzyme known to deactivate dihydrotestosterone. These and other studies demonstrate the flexibility of P450 19A1 in removing the 1- and 2-hydrogens from 19-norsteroids, the 2-hydrogen from estrone, and (in this case) the 1-, 5beta-, and 9beta-hydrogens of dihydrotestosterone. Incubation of dihydrotestosterone with human liver microsomes and NADPH yielded the 18- and 19-hydroxy products plus the Delta(1,10) dehydro 19-nor product identified in the P450 19A1 reaction. The 18- and 19 hydroxylation reactions were attributed to P450 3A4, and 18- and 19 hydroxydihydrotestosterone were identified in human plasma and urine samples. The change in the pucker of the A ring caused by reduction of the Delta(4,5) bond is remarkable in shifting the course of hydroxylation from the 6beta-, 2beta-, 1beta , and 15beta-methylene carbons (testosterone) to the axial methyl groups (18, 19) in dihydrotestosterone and demonstrates the sensitivity of P450 3A4, even with its large active site, to small changes in substrate structure. PMID- 22773876 TI - GATA-binding protein 4 (GATA-4) and T-cell acute leukemia 1 (TAL1) regulate myogenic differentiation and erythropoietin response via cross-talk with Sirtuin1 (Sirt1). AB - Erythropoietin (EPO), the cytokine required for erythrocyte production, contributes to muscle progenitor cell proliferation and delay myogenic differentiation. However, the underlying mechanism is not yet fully understood. Here, we report that EPO changes the skeletal myogenic regulatory factor expression program and delays differentiation via induction of GATA-4 and the basic helix-loop-helix TAL1 and that knockdown of both factors promotes differentiation. EPO increases the Sirt1 level, a NAD(+)-dependent deacetylase, and also induces the NAD(+)/NADH ratio that further increases Sirt1 activity. Sirt1 knockdown reduced GATA-4 and TAL1 expression, impaired EPO effect on delayed myogenic differentiation, and the Sirt1 knockdown effect was abrogated when combined with overexpression of GATA-4 or TAL1. GATA-4 interacts with Sirt1 and targets Sirt1 to the myogenin promoter and represses myogenin expression, whereas TAL1 inhibits myogenin expression by decreasing MyoD binding to and activation of the myogenin promoter. Sirt1 was found to bind to the GATA-4 promoter to directly regulate GATA-4 expression and GATA-4 binds to the TAL1 promoter to regulate TAL1 expression positively. These data suggest that GATA-4, TAL1, and Sirt1 cross-talk each other to regulate myogenic differentiation and mediate EPO activity during myogenic differentiation with Sirt1 playing a role upstream of GATA-4 and TAL1. Taken together, our findings reveal a novel role for GATA-4 and TAL1 to affect skeletal myogenic differentiation and EPO response via cross-talk with Sirt1. PMID- 22773879 TI - Strategies for Longitudinal Research with Youth in Foster Care: A Demonstration of Methods, Barriers, and Innovations. AB - Longitudinal research on youth in foster care is important, but often challenging to accomplish. To assist the field, a thorough description of the development of the SPARK (Studying Pathways to Adjustment and Resilience in Kids) project, a longitudinal research project on the mechanisms of resilience for foster youth and their caregivers, is presented. Authors explain the difficult task for researchers in accessing youth in foster care and suggest strategies for success. Recruitment approaches for foster youth and their families are also provided along with examples of effective techniques. Data collection concerns are discussed, and the authors provide recommendations for researchers to consider when asking youth sensitive questions. Finally, data collection on academic information from teachers and how the SPARK project works with the academic community to gain information on school functioning for youth in the project is described. Suggestions for methodology utilized in future research along with examples of innovative adjustments to typical research procedures are provided as guidance for how research on maltreated youth can be conducted. PMID- 22773878 TI - Fatty acids bind tightly to the N-terminal domain of angiopoietin-like protein 4 and modulate its interaction with lipoprotein lipase. AB - Angiopoietin-like protein 4 (Angptl4), a potent regulator of plasma triglyceride metabolism, binds to lipoprotein lipase (LPL) through its N-terminal coiled-coil domain (ccd-Angptl4) inducing dissociation of the dimeric enzyme to inactive monomers. In this study, we demonstrate that fatty acids reduce the inactivation of LPL by Angptl4. This was the case both with ccd-Angptl4 and full-length Angptl4, and the effect was seen in human plasma or in the presence of albumin. The effect decreased in the sequence oleic acid > palmitic acid > myristic acid > linoleic acid > linolenic acid. Surface plasmon resonance, isothermal titration calorimetry, fluorescence, and chromatography measurements revealed that fatty acids bind with high affinity to ccd-Angptl4. The interactions were characterized by fast association and slow dissociation rates, indicating formation of stable complexes. The highest affinity for ccd-Angptl4 was detected for oleic acid with a subnanomolar equilibrium dissociation constant (K(d)). The K(d) values for palmitic and myristic acid were in the nanomolar range. Linoleic and linolenic acid bound with much lower affinity. On binding of fatty acids, ccd-Angptl4 underwent conformational changes resulting in a decreased helical content, weakened structural stability, dissociation of oligomers, and altered fluorescence properties of the Trp-38 residue that is located close to the putative LPL-binding region. Based on these results, we propose that fatty acids play an important role in modulating the effects of Angptl4. PMID- 22773881 TI - "Raising Him ... to Pull His Own Weight": Boys' Household Work in Single- Mother Households. AB - In this study, the authors examine boys' household work in low- and moderate income single-mother families. Through describing the work that boys do, why they do this work, and the meaning that they and their mothers give to this work, they add to the understanding of housework as an arena for gender role reproduction or interruption. Their data reveal that adolescent boys did a significant amount of work and took pride in their competence. Mothers grounded their expectations of boys' household contributions in life experience. They both needed their sons' day-to-day contributions and wanted their sons to grow into men who were competent around the house and good partners. In demanding household work from their sons, these single mothers themselves work to undermine the traditional gendered division of such labor. PMID- 22773884 TI - Social Quality: A Way to Measure the Quality of Society. AB - In this paper we suggest a way to measure the well-being of society based upon our own development of the Social Quality model. The Social Quality model has the advantage of being sociologically grounded as a measure of the well-being of society and the individuals within it. We test our model of Social Quality against life satisfaction as an indicator of how successful it is in delivering these aspirations. The model was tested on all European countries using the European Quality of Life Surveys in 2003 and 2007 and was found to explain a large amount of variance, which was consistent across time and space. We suggest that it is possible to operationalise this model using small number of variables, ones that are frequently used in comparative surveys and this should enable the quality of society to be measured in a parsimonious and effective way. PMID- 22773880 TI - Self-Serving Bias or Simply Serving the Self? Evidence for a Dimensional Approach to Narcissism. AB - Previous research has suggested that narcissism can be conceptualized as a multidimensional construct consisting of the related, but unique, dimensions of grandiosity and entitlement. The current studies examined the divergent associations of grandiosity and entitlement with respect to different types of self-serving strategies. In Study 1, we found that narcissistic grandiosity, but not entitlement, was positively associated with a self-enhancing strategy of unrealistic optimism. This association was not mediated by self-esteem. In Study 2, narcissistic entitlement, but not grandiosity, was predictive of unethical decision-making, an interpersonal self-promotional strategy that advances the self at the expense of others. Together, both studies support a model of narcissism consisting of a relatively intrapersonal dimension of grandiosity and a relatively interpersonal dimension of entitlement. PMID- 22773877 TI - Identification of Akt-independent regulation of hepatic lipogenesis by mammalian target of rapamycin (mTOR) complex 2. AB - Mammalian target of rapamycin complex 2 (mTORC2) is a key activator of protein kinases that act downstream of insulin and growth factor signaling. Here we report that mice lacking the essential mTORC2 component rictor in liver (Lrictor(KO)) are unable to respond normally to insulin. In response to insulin, Lrictor(KO) mice failed to inhibit hepatic glucose output. Lrictor(KO) mice also fail to develop hepatic steatosis on a high fat diet and manifest half-normal serum cholesterol levels. This is accompanied by lower levels of expression of SREBP-1c and SREBP-2 and genes of fatty acid and cholesterol biosynthesis. Lrictor(KO) mice had defects in insulin-stimulated Akt Ser-473 and Thr-308 phosphorylation, leading to decreased phosphorylation of Akt substrates FoxO, GSK 3beta, PRAS40, AS160, and Tsc2. Lrictor(KO) mice also manifest defects in insulin activated mTORC1 activity, evidenced by decreased S6 kinase and Lipin1 phosphorylation. Glucose intolerance and insulin resistance of Lrictor(KO) mice could be fully rescued by hepatic expression of activated Akt2 or dominant negative FoxO1. However, in the absence of mTORC2, forced Akt2 activation was unable to drive hepatic lipogenesis. Thus, we have identified an Akt-independent relay from mTORC2 to hepatic lipogenesis that separates the effects of insulin on glucose and lipid metabolism. PMID- 22773885 TI - Magnetic Relaxometry with an Atomic Magnetometer and SQUID Sensors on Targeted Cancer Cells. AB - Magnetic relaxometry methods have been shown to be very sensitive in detecting cancer cells and other targeted diseases. Superconducting Quantum Interference Device (SQUID) sensors are one of the primary sensor systems used in this methodology because of their high sensitivity with demonstrated capabilities of detecting fewer than 100,000 magnetically-labeled cancer cells. The emerging technology of atomic magnetometers (AM) represents a new detection method for magnetic relaxometry with high sensitivity and without the requirement for cryogens. We report here on a study of magnetic relaxometry using both AM and SQUID sensors to detect cancer cells that are coated with superparamagnetic nanoparticles through antibody targeting. The AM studies conform closely to SQUID sensor results in the measurement of the magnetic decay characteristics following a magnetization pulse. The AM and SQUID sensor data are well described theoretically for superparamagnetic particles bound to cells and the results can be used to determine the number of cells in a cell culture or tumor. The observed fields and magnetic moments of cancer cells are linear with the number of cells over a very large range. The AM sensor demonstrates very high sensitivity for detecting magnetically labeled cells does not require cryogenic cooling and is relatively inexpensive. PMID- 22773886 TI - Bilingual processing of ASL-English code-blends: The consequences of accessing two lexical representations simultaneously. AB - Bilinguals who are fluent in American Sign Language (ASL) and English often produce code-blends - simultaneously articulating a sign and a word while conversing with other ASL-English bilinguals. To investigate the cognitive mechanisms underlying code-blend processing, we compared picture-naming times (Experiment 1) and semantic categorization times (Experiment 2) for code-blends versus ASL signs and English words produced alone. In production, code-blending did not slow lexical retrieval for ASL and actually facilitated access to low frequency signs. However, code-blending delayed speech production because bimodal bilinguals synchronized English and ASL lexical onsets. In comprehension, code blending speeded access to both languages. Bimodal bilinguals' ability to produce code-blends without any cost to ASL implies that the language system either has (or can develop) a mechanism for switching off competition to allow simultaneous production of close competitors. Code-blend facilitation effects during comprehension likely reflect cross-linguistic (and cross-modal) integration at the phonological and/or semantic levels. The absence of any consistent processing costs for code-blending illustrates a surprising limitation on dual-task costs and may explain why bimodal bilinguals code-blend more often than they code switch. PMID- 22773887 TI - Quality of Language and Literacy Instruction in Preschool Classrooms Serving At Risk Pupils. AB - Policy-makers, administrators, researchers, and teachers are increasingly vested in ensuring the quality of preschool instruction, particularly in the areas of language and literacy. This research was conducted to characterize the quality of language and literacy instruction in 135 publicly-funded preschool classrooms serving at-risk pupils. As all teachers in these classrooms were implementing the same language and literacy curriculum, we also studied the interrelationships among procedural fidelity to a prescribed curriculum and the quality of language and literacy instruction, determining whether procedural fidelity is associated or disassociated with quality instruction. Results showed that the quality of language and literacy instruction in classrooms was low, with few teachers delivering high quality instruction. Although teachers were able to implement a prescribed language and literacy curriculum with a high degree of procedural fidelity, this was not associated with quality instruction. Few structural characteristics of classrooms of teachers were systematically associated with quality of instruction. Findings have important implications for professional development of teachers by suggesting a need for a sustained and coherent focus on the process of instruction to elevate instructional quality in language and literacy. PMID- 22773888 TI - Variation in safety culture dimensions within and between US and Swiss Hospital Units: an exploratory study. AB - BACKGROUND: The purpose of this study was to explore the variability in safety culture dimensions within and between Swiss and US clinical areas. METHODS: Cross sectional design. The 30-item Safety Attitudes Questionnaire (SAQ) was distributed in 2009 to clinicians involved in direct patient care in medical and surgical units of two Swiss and 10 US hospitals. At the unit level, results were calculated as the percentage of respondents within a unit who reported positive perceptions. MANOVA and ANOVA were used to test for differences between and within US and Swiss hospital units. RESULTS: In total, 1370 clinicians from 54 hospital units responded (response rate 84%), including 1273 nurses and 97 physicians. In Swiss hospital units, three SAQ dimensions were lower (safety climate, p=0.024; stress recognition, p<0.001; and perceptions of management, p<0.001) compared with US hospital units. There was significant variability in four out of six SAQ dimensions (teamwork climate, safety climate, job satisfaction and perceptions of unit management) (p<0.001). Moreover, intraclass correlations indicate that these four dimensions vary more at the unit level than hospital level, whereas stress recognition and working conditions vary more at the hospital level. CONCLUSIONS: The authors found differences in SAQ dimensions at the country, hospital and unit levels. The general emphases placed on teamwork and safety climate in quality and safety efforts appear to be highlighting dimensions that vary more at the unit than hospital level. They suggest that patient safety improvement interventions target unit level changes, and they support the emphasis being placed on teamwork and safety climate, as these vary significantly at the unit level across countries. PMID- 22773889 TI - Uncharted territory: measuring costs of diagnostic errors outside the medical record. AB - CONTEXT: In a past study using unannounced standardised patients (USPs), substantial rates of diagnostic and treatment errors were documented among internists. Because the authors know the correct disposition of these encounters and obtained the physicians' notes, they can identify necessary treatment that was not provided and unnecessary treatment. They can also discern which errors can be identified exclusively from a review of the medical records. OBJECTIVE: To estimate the avoidable direct costs incurred by physicians making errors in our previous study. DESIGN: In the study, USPs visited 111 internal medicine attending physicians. They presented variants of four previously validated cases that jointly manipulate the presence or absence of contextual and biomedical factors that could lead to errors in management if overlooked. For example, in a patient with worsening asthma symptoms, a complicating biomedical factor was the presence of reflux disease and a complicating contextual factor was inability to afford the currently prescribed inhaler. Costs of missed or unnecessary services were computed using Medicare cost-based reimbursement data. SETTING: Fourteen practice locations, including two academic clinics, two community-based primary care networks with multiple sites, a core safety net provider, and three Veteran Administration government facilities. MAIN OUTCOME MEASURES: Contribution of errors to costs of care. RESULTS: Overall, errors in care resulted in predicted costs of approximately $174,000 across 399 visits, of which only $8745 was discernible from a review of the medical records alone (without knowledge of the correct diagnoses). The median cost of error per visit with an incorrect care plan differed by case and by presentation variant within case. CONCLUSIONS: Chart reviews alone underestimate costs of care because they typically reflect appropriate treatment decisions conditional on (potentially erroneous) diagnoses. Important information about patient context is often entirely missing from medical records. Experimental methods, including the use of USPs, reveal the substantial costs of these errors. PMID- 22773891 TI - Failures in communication and information transfer across the surgical care pathway: interview study. AB - BACKGROUND AND OBJECTIVES: Effective communication is imperative to safe surgical practice. Previous studies have typically focused upon the operating theatre. This study aimed to explore the communication and information transfer failures across the entire surgical care pathway. METHODS: Using a qualitative approach, semi-structured interviews were conducted with 18 members of the multidisciplinary team (seven surgeons, five anaesthetists and six nurses) in an acute National Health Service trust. Participants' views regarding information transfer and communication failures at each phase of care, their causes, effects and potential interventions were explored. Interviews were recorded, transcribed verbatim, and submitted to emergent theme analysis. Sampling ceased when categorical and theoretical saturation was achieved. RESULTS: Preoperatively, lack of communication between anaesthetists and surgeons was the most common problem (13/18 participants). Incomplete handover from the ward to theatre (12/18) and theatre to recovery (15/18) were other key problems. Work environment, lack of protocols and primitive forms of information transfer were reported as the most common cause of failures. Participants reported that these failures led to increased morbidity and mortality. Healthcare staff were strongly supportive of the view that standardisation and systematisation of communication processes was essential to improve patient safety. CONCLUSIONS: This study suggests communication failures occur across the entire continuum of care and the participants opined that it could have a potentially serious impact on patient safety. This data can be used to plan interventions targeted at the entire surgical pathway so as to improve the quality of care at all stages of the patient's journey. PMID- 22773892 TI - Automated electronic reminders to prevent miscommunication among primary medical, surgical and anaesthesia providers: a root cause analysis. AB - In this case report, the authors present an adverse event possibly caused by miscommunication among three separate medical teams at their hospital. The authors then discuss the hospital's root cause analysis and its proposed solutions, focusing on the subsequent hospital-wide implementation of an automated electronic reminder for abnormal laboratory values that may have helped to prevent similar medical errors. PMID- 22773893 TI - Attenuated total reflectance Fourier-transform infrared spectroscopic imaging for breast histopathology. AB - Histopathology forms the gold standard for the diagnosis of breast cancer. Fourier Transform Infrared (FT-IR) spectroscopic imaging has been proposed to be a potentially powerful adjunct to current histopathological techniques. Most studies using FT-IR imaging for breast tissue analysis have been in the transmission or transmission-reflection mode, in which the wavelength and optics limit the data to a relatively coarse spatial resolution (typically, coarser than 5 MUm * 5 MUm per pixel). This resolution is insufficient to examine many histologic structures. Attenuated Total Reflectance (ATR) FT-IR imaging incorporating a Germanium optic can allow for a four-fold increase in spatial resolution due to the material's high refractive index in the mid-IR. Here, we employ ATR FT-IR imaging towards examining cellular and tissue structures that constitute and important component of breast cancer diagnosis. In particular, we resolve and chemically characterize endothelial cells, myoepithelial cells and terminal ductal lobular units. Further extending the ability of IR imaging to examine sub-cellular structures, we report the extraction of intact chromosomes from a breast cancer cells and their spatially localized analysis as a novel approach to understand changes associated with the molecular structure of DNA in breast cancer. PMID- 22773894 TI - Electromechanical performance of piezoelectric scanning mirrors for medical endoscopy. AB - The electromechanical performance of piezoelectric scanning mirrors for endoscopy imaging is presented. The devices are supported by a single actuating cantilever to achieve a high fill factor, the ratio of mirror area to the combined mirror and actuator area. The largest fill factor devices (74%) achieved 10 degrees mechanical scan range at +/-10V with a 300 MUm long cantilever. The largest angular displacement of 30 degrees mechanical scan range was obtained with a 500 MUm long cantilever device with a 63% fill factor driven at 40 Vpp. A systematic investigation of device performance (displacement and speed) as a function of fabrication and operational parameters including the stress balance in the cantilever revealed unexpectedly large displacements with lack of inversion at the coercive field. An interpretation of the results is presented based on piezoelectric film domain orientation and clamping with supporting piezoelectric film characterization measurements. PMID- 22773895 TI - Computational Analysis of Muscular Dystrophy Sub-types Using A Novel Integrative Scheme. AB - To construct biologically interpretable gene sets for muscular dystrophy (MD) sub type classification, we propose a novel computational scheme to integrate protein protein interaction (PPI) network, functional gene set information, and mRNA profiling data. The workflow of the proposed scheme includes the following three major steps: firstly, we apply an affinity propagation clustering (APC) approach to identify gene sub-networks associated with each MD sub-type, in which a new distance metric is proposed for APC to combine PPI network information and gene gene co-expression relationship; secondly, we further incorporate functional gene set knowledge, which complements the physical PPI information, into our scheme for biomarker identification; finally, based on the constructed sub-networks and gene set features, we apply multi-class support vector machines (MSVMs) for MD sub-type classification, with which to highlight the biomarkers contributing to sub-type prediction. The experimental results show that our scheme can help identify sub-networks and gene sets that are more relevant to MD than those constructed by other conventional approaches. Moreover, our integrative strategy improves the prediction accuracy substantially, especially for those 'hard-to classify' sub-types. PMID- 22773896 TI - Forensic Interviewing Aids: Do Props Help Children Answer Questions About Touching? AB - The belief that props help children report abuse has fostered the widespread use of anatomical dolls and body diagrams in forensic interviews. Yet studies involving alleged abuse victims, children who have experienced medical examinations, and children who have participated in staged events have failed to find consistent evidence that props improve young children's ability to report key information related to bodily contact. Because props elevate the risk of erroneous touch reports, interviewers need to reconsider the belief that props are developmentally appropriate in forensic interviews, and researchers need to explore new approaches for eliciting disclosures of inappropriate touching. PMID- 22773897 TI - The Nature and Organization of Individual Differences in Executive Functions: Four General Conclusions. AB - Executive functions (EFs)-a set of general-purpose control processes that regulate one's thoughts and behaviors-have become a popular research topic lately and have been studied in many subdisciplines of psychological science. This article summarizes the EF research that our group has conducted to understand the nature of individual differences in EFs and their cognitive and biological underpinnings. In the context of a new theoretical framework that we have been developing (the unity/diversity framework), we describe four general conclusions that have emerged from our research. Specifically, we argue that individual differences in EFs, as measured with simple laboratory tasks, (1) show both unity and diversity (different EFs are correlated yet separable); (2) reflect substantial genetic contributions; (3) are related to various clinically and societally important phenomena; and (4) show some developmental stability. PMID- 22773898 TI - On the three-dimensional vortical structure of early diastolic flow in a patient specific left ventricle. AB - We study the formation of the mitral vortex ring during early diastolic filling in a patient-specific left ventricle using direct numerical simulation. The geometry of the left ventricle is reconstructed from Magnetic Resonance Imaging (MRI). The heart wall motion is modeled by a cell-based activation methodology, which yields physiologic kinematics with heart rate equal to 52 beats per minute. We show that the structure of the mitral vortex ring consists of the main vortex ring and trailing vortex tubes, which originate at the heart wall. The trailing vortex tubes play an important role in exciting twisting circumferential instability modes of the mitral vortex ring. At the end of diastole, the vortex ring impinges on the wall and the intraventricular flow transitions to a weak turbulent state. Our results can be used to help interprete and analyze three dimensional in-vivo flow measurements obtained with MRI. PMID- 22773899 TI - Characterizing Fatigue: The Effects of Ethnicity and Acculturation. AB - It is unknown if fatigue measures like the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF; Stein, Jacobsen, Blanchard, & Thors, 2004) appropriately describe fatigue in Hispanics or if acculturation plays a role in fatigue. This study compared fatigue in community samples of Hispanics and Anglos. The MFSI-SF and pertinent questionnaires were administered to adults in San Diego County via telephone survey. Some differences in fatigue were observed in initial comparisons between Hispanics and Anglos, including when acculturation was considered. When age and education were controlled, Hispanics reported less general fatigue than Anglos, regardless of acculturation status, p = < .01. Exploratory factor analyses indicate that the MFSI-SF general-fatigue subscale was problematic for Hispanics. Implications, limitations, and future directions are discussed. PMID- 22773900 TI - Effects of biomarkers of oxidative stress damage on prevalence and severity of visual disability among black Central Africans. AB - BACKGROUND: Because of the demographic transition, lifestyle changes, urbanization, and nutrition transition, Central Africans are at higher risk of ocular diseases associated with oxidative stress and visual disability. This study aimed to estimate the normal values of oxidant status defined by oxidized low-density lipoprotein (Ox-LDL), 8-Isoprostane and 8-hydroxy-deoxyguanosine (8 OHdG) and to determine their pathogenic role in the prevalence and the severity of visual disability among these black Africans. METHODS: This was a cross sectional study, run in a case-control study randomly selected from Kinshasa province, DR Congo. The study included 150 type 2 diabetes mellitus (T2DM) patients (cases) matched for sex and age to 50 healthy non diabetic controls. Logistic regression models were used to identify independent determinants of visual disability. RESULTS: The presence rates were 8.5% for blindness, 20.5% for visual impairment and 29% for visual disability including blindness and visual impairment. After adjusted for taro leaves intake, red beans intake, T2DM, aging, waist circumference, and systolic blood pressure, we identified low education level (OR=3.3 95%CI 1.5-7.2; p=0.003), rural-urban migration (OR=2.6 95% CI 1.2 5.6; p=0.017), and high Ox-LDL (OR=2.3 95% CI 1.1-4.7; p=0.029) as the important independent determinants of visual disability. After adjusted for education, intake of red beans, intake of taro leaves, triglycerides, and T2DM, we identified no intake of safou fruit (OR=50.7 95% CI 15.2-168.5; p<0.0001), rural urban migration (OR=3.9 95%CI 1.213; p=0.012), and high 8-OHdG (OR=14.7 95% CI 3.9-54.5; p<0.0001) as the significant independent determinants of visual disability. After adjusted for education level, no intake of red beans, no intake of Taro leaves, triglycerides, and T2DM, we identified no intake of Safou fruit (OR=43.1 95% CI 13.7-135.4; p<0.0001), age >= 60 years (OR=3.4 95% CI 1.3-9; p=0.024), and high 8-Isoprostane (OR=11 95% CI 3.4-36.1; p<0.0001) as the significant independent determinants of visual disability. CONCLUSIONS: Visual disability remains a public health problem in Central Africa. Antioxidant supplement, fruit intake, nutrition education, control of migration, and blocking of oxidative stress are crucial steps for delayed development of vision loss. PMID- 22773901 TI - SNP rs1533428 at 2p16.3 as a marker for late-onset primary open-angle glaucoma. AB - PURPOSE: To investigate the associations between gene variants in cholesterol 24S hydroxylase (CYP46A1), LIM homeobox transcription factor 1-beta (LMX1B), plexin domain containing 2 (PLXDC2), toll-like receptor 4 (TLR4), transmembrane and tetratricopeptide repeat containing 2 (TMTC2), zona pellucida glycoprotein 4 (ZP4), chromosome 2p16.3, and primary open-angle glaucoma (POAG). METHODS: We studied 462 POAG patients and 577 controls from three cohorts (Hong Kong, Shantou, and Beijing, China). Twelve single-nucleotide polymorphisms (SNPs) were genotyped in the Hong Kong cohort using TaqMan genotyping assay. Significant associations were validated in the Shantou and Beijing cohorts. RESULTS: Association of POAG with TLR4 rs7037117, in a recessive model, was identified in the Hong Kong and Shantou cohorts (both southern Chinese, p(rec)=0.0019) but not the Beijing cohort (northern Chinese). rs1533428 at chromosome 2p16.3 showed a consistent trend of age-specific association in all three cohorts. Genotypes TT + CT conferred a 2.16 fold of significantly increased risk to late-onset POAG (p(dom)=0.00025), but no significant risk to POAG of younger ages of onset in the combined cohort. A joint effect was found between rs7037117 and rs1533428, with carriers of both higher-risk genotypes having a 4.53 fold of increased disease risk (p=0.00028). CONCLUSIONS: Our study reveals discrepant association patterns of 12 candidate SNPs in 7 genes/loci with POAG in Chinese, provides positive replications for POAG markers rs1533428 at 2p16.3 and TLR4 rs7037117, and suggests that rs1533428 is a putative risk variant for late-onset POAG. The identification of an age-specific association between rs1533428 and late-onset POAG highlights a new genotype-phenotype association in POAG. Further studies are warranted to confirm the age-specific association. PMID- 22773903 TI - Phosphomannopentaose sulfate (PI-88) suppresses angiogenesis by downregulating heparanase and vascular endothelial growth factor in an oxygen-induced retinal neovascularization animal model. AB - PURPOSE: Vascular endothelial growth factor (VEGF) is the most potent angiogenic mitogen, and has been associated with angiogenesis. Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains, which can induce VEGF expression. The aims of the present study were to evaluate the heparanase expression and its relationship with VEGF in the retina of oxygen induced retinopathy (OIR) mice, and to investigate the effect of the heparanase inhibitor phosphomannopentaose sulfate (PI-88) in the OIR retinas. METHODS: Seventy-seven newborn C57BL/6 mice were involved in this study. On postnatal day 7 (P7), pups were exposed to a hyperoxia condition (75% oxygen) for 5 days, and on P12, the mice were returned to room air. Control mice were exposed to room air from birth until P17, with normally developing retinal vasculature. PI-88 was administered intraperitoneally to OIR mice at a dose of 35.7 mg/kg/day for 5 consecutive days. The expression level of heparanase and VEGF in the retinas was assayed using immunohistochemistry, Q-RT-PCR, and western blot. RESULTS: The expression levels of heparanase and VEGF were increased in the OIR retinas compared with the control mice. The Q-RT-PCR results showed that the mRNA expression levels of heparanase and VEGF in OIR retina were increased 1.71 fold (p<0.0001) and 4.34 fold (p<0.0001), respectively. The western blot results showed that the protein expression levels of heparanase and VEGF were increased 1.49 fold (p<0.0001) and 1.72 fold (p<0.0001), respectively, in the OIR retinas compared with the normal retinas. The immunohistochemistry analysis revealed that the heparanase and VEGF signals were intense in the retinal vascular endothelia of the OIR mice but faint in those of the normal controls. The increased protein and mRNA expression levels of heparanase and VEGF in the mouse retinas were significantly decreased by PI-88 administration (p<0.0001). CONCLUSIONS: Heparanase expression was upregulated and correlated with an increase in VEGF expression in the OIR mouse retinas, and might be involved in the progress of retinopathy of prematurity. Inhibition of heparanase expression by PI-88 could be used as a novel therapeutic method for retinopathy of prematurity. PMID- 22773902 TI - Effects of melatonin and its receptor antagonist on retinal pigment epithelial cells against hydrogen peroxide damage. AB - PURPOSE: Recently, we reported finding that circulating melatonin levels in age related macular degeneration patients were significantly lower than those in age matched controls. The purpose of this study was to investigate the hypothesis that melatonin deficiency may play a role in the oxidative damage of the retinal pigment epithelium (RPE) by testing the protective effect of melatonin and its receptor antagonist on RPE cells exposed to H(2)O(2) damage. METHODS: Cultured human RPE cells were subjected to oxidative stress induced by 0.5 mM H(2)O(2). Cell viability was measured using the microculture tetrazoline test (MTT) assay. Cells were pretreated with or without melatonin for 24 h. Luzindole (50 MUM), a melatonin membrane-receptor antagonist, was added to the culture 1 h before melatonin to distinguish direct antioxidant effects from indirect receptor dependent effects. All tests were performed in triplicate. RESULTS: H(2)O(2) at 0.5 mM decreased cell viability to 20% of control levels. Melatonin showed dose dependent protective effects on RPE cells against H(2)O(2). Cell viability of RPE cells pretreated with 10(-10), 10(-8), 10(-6), and 10(-4) M melatonin for 24 h was 130%, 160%, 187%, and 230% of cells treated with H(2)O(2) alone (all p<0.05). Using cells cultured without H(2)O(2) as the control, cell viability of cells treated with H(2)O(2) after pretreatment with 10(-10)-10(-4) M melatonin was still significantly lower than that of the controls, suggesting that melatonin significantly decreased but did not completely abolish the in vitro cytotoxic effects of H(2)O(2). Luzindole completely blocked melatonin's protective effects at low concentrations of melatonin (10(-10)-10(-8) M) but not at high concentrations (10(-6)-10(-4) M). CONCLUSIONS: Melatonin has a partial protective effect on RPE cells against H(2)O(2) damage across a wide range of concentrations (10(-10)-10(-4) M). This protective effect occurs through the activation of melatonin membrane receptors at low concentrations (10(-10)-10(-8) M) and through both the direct antioxidant and indirect receptor activation effects at high concentrations (10(-6)-10(-4) M). PMID- 22773904 TI - Sequential in-office vitreous aspirates demonstrate vitreous matrix metalloproteinase 9 levels correlate with the amount of subretinal fluid in eyes with wet age-related macular degeneration. AB - PURPOSE: To evaluate levels of 37 native pathway proteins of the vitreous proteome from a subset of wet age-related macular degeneration (AMD) patients with and without subretinal fluid (SRF). METHODS: A total of 62 consecutive samples were aspirated from 12 patients with AMD, six who had SRF at baseline, and six who did not have SRF at any point during the study. Vitreous levels of the 37 native pathway proteins were analyzed in these patients using reverse phase protein microarray technology. At each visit, at which the 62 samples were taken, SRF and central retinal thickness were measured. These values were then compared to the relative intensity level of the 37 proteins screened. RESULTS: In the subset of AMD patients with SRF, the average matrix metalloproteinase 9 (MMP 9), interleukin (IL)-12, Abelson murine leukemia viral oncogene homolog 1 (cABL) Thr735, heme oxygenase-1, Musashi, platelet-derived growth factor receptor beta Tyr751 (PDGFRbeta), IL-8, and BCL-2 associated death promoter (BAD) Ser112 levels in the vitreous were found to be significantly different with a 21%-82% increase in expression compared to those without SRF (p<0.0001). Within the SRF group, there was a positive correlation between the vitreous MMP-9 levels and the SRF level. MMP-9 levels in the vitreous proteome varied with the level of SRF but not retinal edema. Compared to patients without SRF, the patients with initial SRF had persistent or progressive disease. CONCLUSIONS: This is the first prospective case series sequentially monitoring the vitreous proteome in patients with wet AMD. The results suggest that MMP-9 is a proteomic biomarker of SRF accumulation, separate from macular edema. PMID- 22773905 TI - Mutant NADH dehydrogenase subunit 4 gene delivery to mitochondria by targeting sequence-modified adeno-associated virus induces visual loss and optic atrophy in mice. AB - PURPOSE: Although mutated G11778A NADH ubiquinone oxidoreductase subunit 4 (ND4) mitochondrial DNA (mtDNA) is firmly linked to the blindness of Leber hereditary optic neuropathy (LHON), a bona fide animal model system with mutated mtDNA complex I subunits that would enable probing the pathogenesis of optic neuropathy and testing potential avenues for therapy has yet to be developed. METHODS: The mutant human ND4 gene with a guanine to adenine transition at position 11778 with an attached FLAG epitope under control of the mitochondrial heavy strand promoter (HSP) was inserted into a modified self-complementary (sc) adeno-associated virus (AAV) backbone. The HSP-ND4FLAG was directed toward the mitochondria by adding the 23 amino acid cytochrome oxidase subunit 8 (COX8) presequence fused in frame to the N-terminus of green fluorescent protein (GFP) into the AAV2 capsid open reading frame. The packaged scAAV-HSP mutant ND4 was injected into the vitreous cavity of normal mice (OD). Contralateral eyes received scAAV-GFP (OS). Translocation and integration of mutant human ND4 in mouse mitochondria were assessed with PCR, reverse transcription-polymerase chain reaction (RT-PCR), sequencing, immunoblotting, and immunohistochemistry. Visual function was monitored with serial pattern electroretinography (PERG) and in vivo structure with spectral domain optical coherence tomography (OCT). Animals were euthanized at 1 year and processed for light and transmission electron microscopy. RESULTS: The PCR products of the mitochondrial and nuclear DNA extracted from infected retinas and optic nerves gave the expected 500 base pair bands. RT-PCR confirmed transcription of the mutant human ND4 DNA in mice. DNA sequencing confirmed that the PCR and RT-PCR products were mutant human ND4 (OD only). Immunoblotting revealed the expression of mutant ND4FLAG (OD only). Pattern electroretinograms showed a significant decrement in retinal ganglion cell function OD relative to OS at 1 month and 6 months after AAV injections. Spectral domain optical coherence tomography showed optic disc edema starting at 1 month post injection followed by optic nerve head atrophy with marked thinning of the inner retina at 1 year. Histopathology of optic nerve cross sections revealed reductions in the optic nerve diameters of OD versus OS where transmission electron microscopy revealed significant loss of optic nerve axons in mutant ND4 injected eyes where some remaining axons were still in various stages of irreversible degeneration with electron dense aggregation. Electron lucent mitochondria accumulated in swollen axons where fusion of mitochondria was also evident. CONCLUSIONS: Due to the UGA codon at amino acid 16, mutant G11778A ND4 was translated only in the mitochondria where its expression led to significant loss of visual function, loss of retinal ganglion cells, and optic nerve degeneration recapitulating the hallmarks of human LHON. PMID- 22773906 TI - Upregulation of heparanase in high-glucose-treated endothelial cells promotes endothelial cell migration and proliferation and correlates with Akt and extracellular-signal-regulated kinase phosphorylation. AB - PURPOSE: The objectives of this study were to determine whether high-glucose induced upregulation of heparanase (HPSE) expression and differential heparanase expression in human retinal vascular endothelial cells (HRECs) can alter HREC migration and proliferation. We also aimed to determine whether HREC migration and proliferation correlate with the levels of protein kinase B (Akt) and extracellular-signal-regulated kinase (ERK) phosphorylation and activation. METHODS: HRECs were treated with either 5 mM glucose (Glu5) or high (30 mM) glucose (Glu30) for 48 h. Untransfected HRECs were grown in human endothelial serum-free medium (HE-SFM) in the presence of 5 mM glucose and supplemented with 30 mM mannitol for 48 h as an osmotic control (mannitol). HRECs were also infected with a heparanase small interfering RNA recombinant lentiviral vector (HPSE-LV) or a control vector (Con-LV) at a multiplicity of infection (MOI) of 60 for three days. Then the con-LV and HPSE-LV-infected cells were treated with 30 mM glucose for 48 h (Con-LV-Glu30 and HSPE-LV-Glu30, respectively). The expression levels of heparanase mRNA and protein and HREC proliferation and migration were examined using quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis, 3-(4,5-dimethylthiahiazol-2-y1)-2,5 diphenyltetrazolium bromide assay, bromodeoxyuridine histochemical staining, and the Boyden chamber assay. The expression level of paxillin was examined using immunofluorescent staining. Akt and ERK phosphorylation was evaluated using western blot analysis. RESULTS: We successfully transfected the HPSE RNAi lentiviral vector into HRECs and demonstrated that it can suppress the expression of the heparanase gene in these cells. Western blot and qRT-PCR analyses showed that HRECs treated with a high concentration of glucose exhibited increased heparanase protein and mRNA levels, while the levels were decreased in HRECs that had been infected with HPSE-LV before treatment with high glucose (HPSE-LV-Glu30; p<0.05). The observed increase or decrease in the levels of heparanase correlated with increased or decreased HREC migration and proliferation, respectively (p<0.05). HREC proliferation and migration were found to correlate with Akt and ERK phosphorylation levels (p<0.5). CONCLUSIONS: Our results indicate that heparanase plays a significant role in mediating retinal vascular endothelial cell proliferation and migration after the HRECs are exposed to high levels of glucose. Signaling inducing heparanase-stimulated HREC proliferation and migration appears to be related to the activation of Akt and ERK via their phosphorylation. PMID- 22773908 TI - Semiparametric Estimation Methods for the Accelerated Failure Time Mixture Cure Model. AB - This paper provides an overview of two semiparametric estimation methods recently proposed in the literature for the accelerated failure time mixture cure model. We prove that the two estimation methods are asymptotically equivalent. A simulation is conducted to investigate the rate of convergence of the two methods. We apply these methods to fit the accelerated failure time mixture cure model to the survival times of leukemia patients receiving bone marrow transplantation. PMID- 22773909 TI - Revision of the afrotropical oberthuerellinae (cynipoidea, liopteridae). AB - The Afrotropical Oberthuerellinae are revised, and new dichotomous and multi entry keys to the species of Oberthuerella, Tessmannella, and Xenocynips are provided. All previously described species in these genera are redescribed; descriptions are augmented by color images of the holotype for each species. The following 11 species are described as new: Oberthuerella cyclopia Buffington & van Noort; Oberthuerella eschara Buffington & van Noort; Oberthuerella kibalensis van Noort & Buffington; Oberthuerella pardolatus Buffington & van Noort; Oberthuerella sharkeyi Buffington & van Noort; Oberthuerella simba Buffington & van Noort; Tessmannella copelandi Buffington & van Noort; Tessmannella kiplingi Buffington & van Noort; Tessmannella roberti Buffington & van Noort; Xenocynips rhothion Buffington & van Noort; and Xenocynips ronquisti Buffington & van Noort. We provide identification keys to the genera and species occurring in the Afrotropical region. Online dichotomous and interactive Lucid keys to genera and species are available at http://www.waspweb.org/Cynipoidea/Keys/index.htm. PMID- 22773907 TI - Association between the methylene tetrahydrofolate reductase gene C677T mutation and colchicine unresponsiveness in Behcet's disease. AB - PURPOSE: Behcet's disease (BD) is a multisystemic immunoinflammatory disorder characterized by mucocutaneous, ocular, vascular, and central nervous system manifestations. The common methylene tetrahydrofolate reductase (MTHFR) gene C677T mutation is a known risk factor for thrombosis. The aim of this study was to investigate the MTHFR gene C677 mutation in patients with BD and evaluate if there was an association with clinical features, especially thrombosis, in a relatively large cohort of patients with BD. METHODS: The study included 318 patients with BD and 207 healthy controls. Genomic DNA was isolated and genotyped using PCR-based restriction fragment length polymorphism assay for the MTHFR gene C677T mutation. RESULTS: The genotype and allele frequencies of the C677T mutation showed a statistically significant difference between BD patients and controls (p=0.003 and p=0.001, respectively). There was also a significant association between C677T alteration and response to colchicine in BD patients (p=0.046). CONCLUSIONS: The results of this study showed that there was a high association between the MTHFR gene C677T mutation and BD. Stratification analysis according to clinical features for this disease did not reveal an association except response to colchicine that was shown to be influenced by the MTHFR C677T mutation. PMID- 22773910 TI - A new species of Oxelytrum Gistel (Coleoptera, Silphidae) from southern Argentina, with a key to the species of the genus. AB - A new species of the forensically interesting genus Oxelytrum Gistel (Coleoptera, Silphidae), Oxelytrum selknan, is described from Santa Cruz and Tierra del Fuego provinces, Argentina. The new species resembles Oxelytrum biguttatum (Philippi) in outer aspect, but has different male genitalia, in particular a median lobe longer than the paramera. All the described species of Oxelytrum have the median lobe shorter than the paramera. The internal sac, as far as it could be reconstructed from dry-pinned specimens, also shows differences between the two species. A key to the species of Oxelytrum is given and illustrated. PMID- 22773911 TI - Two new species and one newly recorded species of Elaphropeza Macquart from Taiwan (Diptera, Empididae, Tachydromiinae). AB - Previously 11 Elaphropeza species were known from Taiwan. The following two species of the genus Elaphropeza are described: Elaphropeza flaviscutumsp. n. and Elaphropeza trimaculasp. n. One species, Elaphropeza plumata Yang, Merz & Grootaert, is newly recorded from Taiwan. A key to 14 known species of Elaphropeza from Taiwan is presented. PMID- 22773912 TI - A review of the genus Neopsocopsis (Psocodea, "Psocoptera", Psocidae), with one new species from China. AB - A review of species of the genus Neopsocopsis Badonnel, 1936 is presented. Four species are redescribed, viz. Neopsocopsis hirticornis (Reuter, 1893), Neopsocopsis quinquedentata (Li & Yang, 1988), Neopsocopsis profunda (Li, 1995), and Neopsocopsis flavida (Li, 1989), as well as the description of one new species, Neopsocopsis convexasp. n. Seven new synonymies are proposed as follows: Pentablaste obconica Li syn. n. and Pentablaste clavata Li syn. n. of Neopsocopsis hirticornis, Pentablaste tetraedrica Li syn. n. of Neopsocopsis longiptera, Neoblaste schizopetala Li syn. n. and Neoblaste flavae Li syn. n. of Neopsocopsis profunda, Blastopsocidus pini Li syn. n. and Pentablaste lanceolata Li syn. n. of Neopsocopsis flavida. Neopsocopsis hirticornis (Reuter, 1893) is recorded from Japan and China for the first time, and Neopsocopsis longiptera Vishnyakova, 1986 is newly recorded from China. Illustrated keys to adult males and females are presented. PMID- 22773913 TI - A key to known species of Episcapha (subgenus Ephicaspa Chujo) (Coleoptera, Erotylidae, Megalodacnini), with the description of two new species. AB - Two new species Episcapha (Ephicaspa) lushuiensissp. n. and Episcapha (Ephicaspa) quadriconcavasp. n. are described and illustrated from China. A key to known species of subgenus Ephicaspa is provided. A map of the collecting sites is given. PMID- 22773914 TI - Description of Crassolabium persicum sp. n. (Nematoda, Dorylaimida, Qudsianematidae), an interesting species from Iran. AB - A new species of the genus Crassolabium, Crassolabium persicumsp. n., collected from Arasbaran rangelands of Iran, is described and illustrated. It is characterized by its body 1.92-2.40 mm long, lip region offset by constriction and 17-19 MUm wide, odontostyle 16-19 MUm long with aperture occupying less than one-third (27-30%) its length, neck 428-690 MUm long, pharyngeal expansion 369 390 MUm long or occupying 54-56% of total neck length, female genital system amphidelphic, uterus bipartite and 162-218 MUm long or 2.3-3.5 times as long as body diameter, pars refringens vaginae well developed, V = 54-57.5, vulva longitudinal, prerectum bearing a blind sac, tail conical with rounded tip to conoid (25-36 MUm, c=60-69, c'=0.5-0.9), spicules 68-72 MUm long, precloacal pair of supplements far (22-27 MUm) from cloacal aperture, and 13-17 shortly spaced ventromedian supplements with hiatus. The new taxon is compared in depth to its relatives in Crassolabium as well as other similar species of Aporcelaimellus and Amblydorylaimus. PMID- 22773915 TI - Water mites (Acari, Hydrachnidia) from Baishih River drainage in Northern Taiwan, with description of two new species. AB - NEW RECORDS OF WATER MITES (ACARI: Hydrachnidia) from Baishih River drainage of north Taiwan, are presented. Twelve species are recorded, of which ten are new for Taiwan; two of them, Torrenticola projectura and Hygrobates taiwanicus are described as new for science. PMID- 22773916 TI - Dating Violence Prevention Programming: Directions for Future Interventions. AB - Dating violence among college students is a widespread and destructive problem. The field of dating violence has seen a substantial rise in research over the past several years, which has improved our understanding of factors that increase risk for perpetration. Unfortunately, there has been less attention paid to dating violence prevention programming, and existing programs have been marred with methodological weaknesses and a lack of demonstrated effectiveness in reducing aggression. In hopes of sparking new research on dating violence prevention programs, the current review examines possible new avenues for dating violence prevention programming among college students. We discuss clinical interventions that have shown to be effective in reducing a number of problematic behaviors, including motivational interventions, dialectical behavior therapy, mindfulness, and bystander interventions, and how they could be applied to dating violence prevention. We also discuss methodological issues to consider when implementing dating violence prevention programs. PMID- 22773917 TI - Size-Dependent Rupture Strain of Elastically Stretchable Metal Conductors. AB - Experiments show that the rupture strain of gold conductors on elastomers decreases as the conductors are made long and narrow. Rupture is caused by the irreversible coalescence of microcracks into one long crack. A mechanics model identifies a critical crack length l(cr), above which the long crack propagates across the entire conductor width. l(cr) depends on the fracture toughness of the gold film and the width of the conductor. The model provides guidance for the design of highly stretchable conductors. PMID- 22773918 TI - Introduction to the special issue: Recap of ninth International Conference on Health Policy Statistics. PMID- 22773919 TI - Joint modeling of longitudinal outcomes and survival using latent growth modeling approach in a mesothelioma trial. AB - Joint modeling of longitudinal and survival data can provide more efficient and less biased estimates of treatment effects through accounting for the associations between these two data types. Sponsors of oncology clinical trials routinely and increasingly include patient-reported outcome (PRO) instruments to evaluate the effect of treatment on symptoms, functioning, and quality of life. Known publications of these trials typically do not include jointly modeled analyses and results. We formulated several joint models based on a latent growth model for longitudinal PRO data and a Cox proportional hazards model for survival data. The longitudinal and survival components were linked through either a latent growth trajectory or shared random effects. We applied these models to data from a randomized phase III oncology clinical trial in mesothelioma. We compared the results derived under different model specifications and showed that the use of joint modeling may result in improved estimates of the overall treatment effect. PMID- 22773921 TI - Sodium bicarbonate to reduce contrast-induced nephropathy. PMID- 22773920 TI - A Descriptive, Retrospective Study of After-hours Calls in Hospice and Palliative Care. AB - AIMS: Few studies have described after-hours calls in hospice patient care. This retrospective study examines the timing of after-hours telephone triage services; the reasons for access to after-hours hospice and palliative care services; and the predominant nursing interventions offered in after-hours calls in hospice and palliative care. METHODS: A fixed coding scheme was used to code a de-identified after-hours triage phone log of all calls between July 2005 and June 2006 (n=4,434) from a Pennsylvania hospice and palliative care services organization. Descriptive statistics were used to identify call timing pattern, call reasons, and predominant nursing interventions. RESULTS: Triage services were utilized most frequently to request assistance with signs and symptoms control (25.7%), report death (17.8%), and to request a home visit (15.3%). The top nursing interventions included updating case managers or supervisors about the needs of follow-up (29.5%), coordinating home visits (20.5%), and instructing caregivers or patients on how to control new signs and symptoms (19.8%). CONCLUSIONS: A better understanding of when and why patients and their family caregivers utilize after-hours hospice triage services can assist in the design of future proactive interventions to improve care, and enhance training for new and existing hospice triage nurses. PMID- 22773922 TI - P.U.R.E. Communication: A Strategy to Improve Care-Coordination for High Risk Birth. AB - High-risk birth can be an emotionally-charged and sometimes emergent event that requires a cohesive multidisciplinary team. Communication breakdowns in perinatal emergencies are known to contribute to errors and adverse patient outcomes. One approach to breaching these barriers is the Purposeful, Unambiguous, Respectful, and Effective, P.U.R.E. process. P.U.R.E. is a method of communication that emphasizes coordination and recognizes the contributions of each member of the team. The purpose of this article is to describe how the P.U.R.E. process works and how teamwork strategies, group skills training, and structured communication techniques complement it. PMID- 22773923 TI - RSQRT: AN HEURISTIC FOR ESTIMATING THE NUMBER OF CLUSTERS TO REPORT. AB - Clustering can be a valuable tool for analyzing large datasets, such as in e commerce applications. Anyone who clusters must choose how many item clusters, K, to report. Unfortunately, one must guess at K or some related parameter. Elsewhere we introduced a strongly-supported heuristic, RSQRT, which predicts K as a function of the attribute or item count, depending on attribute scales. We conducted a second analysis where we sought confirmation of the heuristic, analyzing data sets from theUCImachine learning benchmark repository. For the 25 studies where sufficient detail was available, we again found strong support. Also, in a side-by-side comparison of 28 studies, RSQRT best-predicted K and the Bayesian information criterion (BIC) predicted K are the same. RSQRT has a lower cost of O(log log n) versus O(n(2)) for BIC, and is more widely applicable. Using RSQRT prospectively could be much better than merely guessing. PMID- 22773925 TI - New Insights into the Molecular Basis of the Antiphospholipid Syndrome. AB - Antiphospholipid syndrome is an autoimmune disease characterized by the presence of circulating antiphospholipid antibodies (aPL) that promote thrombosis, pregnancy complications and cardiovascular diseases. Alterations in the function of vascular cells induced by aPL underlie these outcomes. This review will discuss recent findings that indicate a novel mechanism by which aPL antagonize endothelial cell production of nitric oxide and thereby promote thrombosis. PMID- 22773924 TI - Quantitative Molecular Imaging of Neuronal Nicotinic Acetylcholine Receptors in the Human Brain with A-85380 Radiotracers. AB - Neuronal nicotinic acetylcholine receptors (nAChRs) have been implicated in a spectrum of cognitive functions as well as psychiatric and neurodegenerative disorders, including tobacco addiction and Alzheimer's Disease. The examination of neuronal nAChRs in living humans is a relatively new field. Researchers have developed brain-imaging radiotracers for nAChRs, with radiolabeled A-85380 compounds having the most widespread use. We provide a brief background on nAChRs, followed by a discussion of the development and application of A-85380 radiotracers in human imaging studies. We describe potential future studies using nicotinic receptor radioligands for the study of tobacco addiction, including the mechanism of action of the smoking-cessation therapy varenicline. Throughout this review, we focus on the significant potential that resides in the identification and quantification of nAChRs in the living human brain. PMID- 22773926 TI - Fibrillized peptide microgels for cell encapsulation and 3D cell culture. AB - One of the advantages of materials produced by self-assembly is that in principle they can be formed in any given container to produce materials of predetermined shapes and sizes. Here, we developed a method for triggering peptide self assembly within the aqueous phase of water-in-oil emulsions to produce spherical microgels composed of fibrillized peptides. Size control over the microgels was achieved by specification of blade type, speed, and additional shear steps in the emulsion process. Microgels constructed in this way could then be embedded within other self-assembled peptide matrices by mixing pre-formed microgels with un assembled peptides and inducing gelation of the entire composite, offering a route towards multi-peptide materials with micron-scale domains of different peptide formulations. The gels themselves were cytocompatible, as was the microgel fabrication procedure, enabling the encapsulation of NIH 3T3 fibroblasts and C3H10T-1/2 mouse pluripotent stem cells with good viability. PMID- 22773927 TI - Memory Interference as a Determinant of Language Comprehension. AB - The parameters of the human memory system constrain the operation of language comprehension processes. In the memory literature, both decay and interference have been proposed as causes of forgetting; however, while there is a long history of research establishing the nature of interference effects in memory, the effects of decay are much more poorly supported. Nevertheless, research investigating the limitations of the human sentence processing mechanism typically focus on decay-based explanations, emphasizing the role of capacity, while the role of interference has received comparatively little attention. This paper reviews both accounts of difficulty in language comprehension by drawing direct connections to research in the memory domain. Capacity-based accounts are found to be untenable, diverging substantially from what is known about the operation of the human memory system. In contrast, recent research investigating comprehension difficulty using a retrieval-interference paradigm is shown to be wholly consistent with both behavioral and neuropsychological memory phenomena. The implications of adopting a retrieval-interference approach to investigating individual variation in language comprehension are discussed. PMID- 22773928 TI - Quality matters! Differences between expressive and receptive non-verbal communication skills in adolescents with ASD. AB - We analyzed several studies of non-verbal communication (prosody and facial expressions) completed in our lab and conducted a secondary analysis to compare performance on receptive vs. expressive tasks by adolescents with ASD and their typically developing peers. Results show a significant between-group difference for the aggregate score of expressive tasks, but not for the aggregate score of receptive tasks. There was also a significant within-group difference among individuals with ASD for expressive vs. receptive performance. Our data indicate that adolescents with ASD can achieve receptive accuracy in non-verbal communication, but show significant qualitative deficits in expressive skills across a range of tasks, which may have a significant negative impact on their success as social communicators. PMID- 22773930 TI - A Mathematical Model of Human Papillomavirus (HPV) in the United States and its Impact on Cervical Cancer. AB - BACKGROUND: Mathematical models can be useful tools in exploring disease trends and health consequences of interventions in a population over time. Most cancers, in particular cervical cancer, have long incubation periods. The time from acquisition of HPV infection to development of invasive cancer can be up to two decades or more. Mathematical models can be used to translate short-term findings from prevention and mitigations trials into predictions of long-term health outcomes. The main objective of this paper is to develop a mathematical model of HPV for African American women (AAW) in the United States and give quantitative insight into current U.S. prevention and mitigations against cervical cancer. METHODS: A compartmental mathematical model of the cycle of HPV that includes the choices individuals make once they become infected; treatment versus no treatment, was developed. Using this mathematical model we evaluated the impact of human papillomavirus (HPV) on a given population and determined what could decrease the rate at which AAW become infected. All state equations in the model were approximated using the Runge-Kutta 4(th) order numerical approximation method using MatLab software. RESULTS: In this paper we found that the basic reproductive number R(OU) is directly proportional to the rate of infectivity of HPV and the contact rate in which a human infects another human with HPV. The R(OU) was indirectly proportional to the recovery rate plus the mortality by natural causes and the disease. The second R(OT) is also directly proportional to the rate of infectivity of HPV and contact rate in which humans infect another human with HPV and indirectly proportional to the recovery rate plus the mortality from HPV related cause and natural causes. Based on the data of AAW for the parameters; we found that R(OU) and R(OT)were 0.519798 and 0.070249 respectively. As both of these basic reproductive numbers are less than one, infection cannot therefore get started in a fully susceptible population, however, if mitigation is to be implemented effectively it should focus on the HPV untreated population as R(OT)is greater than 0.5. CONCLUSION: Mathematical models, from individual and population perspectives, will help decision makers to evaluate different prevention and mitigation measures of HPV and deploy synergistically to improve cancer outcomes. Integrating the best-available epidemiologic data, computer-based mathematical models used in a decision analytic framework can identify those factors most likely to influence outcomes and can help in formulating decisions that need to be made amidst considerable lack of data and uncertainty. Specifically, the model provides a tool that can accommodate new information, and can be modified as needed, to iteratively assess the expected benefits, costs, and cost-effectiveness of different policies in the United States. This model can help show the direct relationship between HPV and cervical cancer. If any of the rates change it will greatly impact the graphs. These graphs can be used to discover new methods of treatment that will decrease the rate of infectivity of HPV and Cervical cancer with time. PMID- 22773929 TI - Role of CT perfusion imaging in the diagnosis and treatment of vasospasm. AB - The current role of CT perfusion (CTP) imaging in the diagnosis and treatment of vasospasm in the setting of aneurysmal subarachnoid hemorrhage is discussed in this article, with specific attention directed towards defining the terminology of vasospasm and delayed cerebral ischemia. A commonly used CTP technique in clinical practice is described. A review of the literature regarding the usefulness of CTP for the diagnosis of vasospasm and its role in guiding treatment are discussed. Recent research advances in the utilization of CTP and associated ongoing challenges are also presented. PMID- 22773932 TI - Analysis of pancreatic cancer microenvironment: role of macrophage infiltrates and growth factors expression. AB - BACKGROUND: Research over the last twenty years has yielded much insight into pancreatic cancer biology, but it has neither improved diagnostics methods nor the way of treatment. The question remains as to what the critical deciding factor is in making pancreatic cancer such an aggressive disease. METHODS: Pancreatic tumor tissue came from 36 patients. To assess lymphatic vessels color lymphangiography and immunohistochemistry were used. Activity of matrix metalloproteinases was studied with gel and in situ zymography. Expression of growth factors and infiltrating immune cells were investigated using immunohistochemistry. RESULTS: Our study revealed that the structures that correspond to lymphatic vessels were not observed in tumor center but only at the edge of the tumor. All studied growth factors were present in tumor tissue. We found that the difference in expression between G2 and G3 stage was statistically relevant in cases of c-Met receptor. Inflammatory cells were present around neoplastic glands and also strongly around nerves infiltrated by cancer cells. The number of infiltrating macrophages in tumor tissue was significantly higher in group with metastases to lymph nodes. CONCLUSION: We showed two factors that influence pancreatic cancer progression and invasion: c-Met receptors and macrophages infiltrating tumor tissue. Based on our analysis, this indicates that epithelial-mesenchymal transition might be crucial in the progression of pancreatic cancer. PMID- 22773933 TI - Trends of incidence and survival of gastrointestinal neuroendocrine tumors in the United States: a seer analysis. AB - OBJECTIVES: To examine trends in detection and survival of hollow viscus gastrointestinal neuroendocrine tumors (NETs) across time and geographic regions of the U.S. METHODS: We used the Surveillance, Epidemiology and End Results (SEER) database to investigate 19,669 individuals with newly diagnosed gastrointestinal NETs. Trends in incidence were tested using Poisson regression. Cox proportional hazards regression was used to examine survival. RESULTS: Incidence increased over time for NETs of all gastrointestinal sites (all P < 0.001), except appendix. Rates have risen faster for NETs of the small intestine and rectum than stomach and colon. Rectal NETs were detected at a faster pace among blacks than whites (P < 0.001) and slower in the East than other regions (P < 0.001). We observed that appendiceal and rectal NETs carry the best prognosis and survival of small intestinal and colon NETs has improved for both men and women. Colon NETs showed different temporal trends in survival according to geographic region (P(interaction) = 0.028). Improved prognosis was more consistent across the country for small intestinal NETs. CONCLUSIONS: Incidence of gastrointestinal NETs has increased, accompanied by inconsistently improved survival for different anatomic sites among certain groups defined by race and geographic region. PMID- 22773931 TI - Identification of Potential Glycoprotein Biomarkers in Estrogen Receptor Positive (ER+) and Negative (ER-) Human Breast Cancer Tissues by LC-LTQ/FT-ICR Mass Spectrometry. AB - Breast cancer is the second most fatal cancer in American women. To increase the life expectancy of patients with breast cancer new diagnostic and prognostic biomarkers and drug targets must be identified. A change in the glycosylation on a glycoprotein often causes a change in the function of that glycoprotein; such a phenomenon is correlated with cancerous transformation. Thus, glycoproteins in human breast cancer estrogen receptor positive (ER+) tissues and those in the more advanced stage of breast cancer, estrogen receptor negative (ER-) tissues, were compared. Glycoproteins showing differences in glycosylation were examined by 2-dimensional gel electrophoresis with double staining (glyco- and total protein staining) and identified by reversed-phase nano-liquid chromatography coupled with a hybrid linear quadrupole ion trap/ Fourier transform ion cyclotron resonance mass spectrometer. Among the identified glycosylated proteins are alpha 1 acid glycoprotein, alpha-1-antitrypsin, calmodulin, and superoxide dismutase mitochondrial precursor that were further verified by Western blotting for both ER+ and ER- human breast tissues. Results show the presence of a possible glycosylation difference in alpha-1-antitrypsin, a potential tumor-derived biomarker for breast cancer progression, which was expressed highest in the ER- samples. PMID- 22773934 TI - Malignant peripheral nerve sheath tumors: differentiation patterns and immunohistochemical features - a mini-review and our new findings. AB - Malignant peripheral nerve sheath tumors (MPNST) represent a group of highly heterogeneous human malignancies often with multiple histological origins, divergent differentiation patterns, and diverse immunohistochemical presentations. The differential diagnosis of MPNST from other spindle cell neoplasms poses great challenges for pathologists. This report provides a mini review of these unique features associated with MPNST and also presents the first cases of MPNST with six differentiation patterns. PMID- 22773935 TI - Chylous ascites occurring after low anterior resection of the rectum successfully treated with an oral fat-free elemental diet (Elental((r))). AB - Chylous ascites occurring after abdominal surgery is rare. Despite being potentially critical, there is no definite treatment guideline because of its rarity. Here we present a case of massive chylous ascites occurring after rectal surgery which was successfully treated with an oral fat-free elemental diet (ED). A 67-year-old man underwent low anterior resection with para-aortic lymphadenectomy for advanced rectal cancer. Early postoperative course was uneventful and the patient was discharged from hospital 10 days after surgery; however, after discharge, abdominal distension rapidly developed. Abdominal computed tomography (CT) performed 3 weeks after surgery revealed massive ascites and laboratory findings showed remarkable hypoproteinemia and lymphopenia. Urgent diagnostic paracentesis showed the ascites to be a white milky fluid containing high levels of triglycerides (564 mg/dl), leading to a diagnosis of chyloperitoneum. Daily nutrition of the patient was entirely with a fat-free ED (30 kcal/kg/day of Elental((r)), Ajinomoto Pharmaceutical Co. Ltd, Tokyo, Japan). After the initiation of oral Elental((r)), abdominal distension, hypoproteinemia, and lymphopenia gradually improved. Abdominal CT performed 7 weeks after surgery showed no ascitic fluid in the abdomen, and thereafter a normal diet was initiated. Since then, no relapse of chyloperitoneum has been proven. As a result, the chylous ascites was successfully treated in the outpatient clinic. PMID- 22773936 TI - Neuregulin-1 effects on endothelial and blood-brain-barrier permeability after experimental injury. AB - Blood-brain-barrier disruption occurs with a high incidence after traumatic brain injury, and is an important contributor to many pathological processes, including brain edema, inflammation, and neuronal cell death. Therefore, blood-brain barrier integrity is an important potential therapeutic target in the treatment of the acute phase of brain trauma. In this short communication, we report our data showing that neuregulin-1 (NRG1), a growth factor with diverse functions in the CNS, ameliorates pathological increases in endothelial permeability and in BBB permeability in experimental models of injury. For in-vitro studies, rat brain endothelial cells were incubated with the inflammatory cytokine IL-1beta, which caused an increase in permeability of the cell layer. Co-incubation with NRG1 ameliorated this permeability increase. For in-vivo studies, C57Bl mice were subjected to controlled cortical impact (CCI) under anesthesia, and BBB permeability was assessed by measuring the amount of Evans blue dye extravasation at 2h. NRG1 administered by tail-vein injection 10 minutes after CCI resulted in a decrease in Evans blue dye extravasation by 35%. Since Evans blue extravasation may result from an increase in BBB permeability or from bleeding due to trauma, hemoglobin ELISA was also performed at the same time point. There was a trend towards lower levels of hemoglobin extravasation in the NRG1 group, but the results did not reach statistical significance. MMP-9 activity was not different between groups at 2h. These data suggest that NRG1 has beneficial effects on endothelial permeability and BBB permeability following experimental trauma, and may have neuroprotective potential during CNS injury. PMID- 22773937 TI - Neurocognitive and clinical dysfunction in adult Chinese, nonpsychotic relatives of patients with schizophrenia: Findings from the Changsha study and evidence for schizotaxia. AB - Many first-degree relatives of patients with schizophrenia demonstrate deficits in neurocognitive, social, clinical and other dimensions, in the absence of psychosis. Based on a reformulation of Meehl's concept of "schizotaxia" as a clinically meaningful syndrome reflecting liability to schizophrenia, we proposed research criteria in relatives focused on negative symptoms and neurocognitive deficits. Here we assess validity of the syndrome in a sample of Chinese adult relatives by assessing measures of concurrent validity, and by using cluster analysis to test the hypothesis that relatives could be grouped into distinct schizotaxic and non-schizotaxic subgroups based on our diagnostic criteria. Thirty community comparison subjects (CCS) and 189 relatives were evaluated with measures of clinical, cognitive, medical and social function at the Mental Health Institute, Second Xiangya Hospital of Central South University, Changsha (Hunan, China), as part of a larger study to identify and ameliorate symptoms of schizotaxia. Using modified research criteria based on negative symptoms and neurocognitive deficits, 103 relatives did not meet criteria for schizotaxia, and 86 did. The cluster analysis confirmed a two-group solution that corresponded to our non-schizotaxic and schizotaxic groups, but it increased the non-schizotaxic group to 135, and reduced the schizotaxic group to 53. Both schizotaxic groups, but especially the cluster-derived group, showed significant impairment in a variety of independent (i.e. non-criterion related) measures of clinical and social function. These findings provide additional validity for a liability syndrome, and for its utility as an intervention target for strategies aimed at ameliorating both its core and its associated symptoms. PMID- 22773938 TI - Remaining Life Expectancy Measurement and PSA Screening of Older Men. AB - BACKGROUND: Guidelines recommend informed decision-making regarding prostate specific antigen (PSA) screening for men with at least 10 years of remaining life expectancy (RLE). Comorbidity measures have been used to judge RLE in previous studies, but assessments based on other common RLE measures are unknown. We assessed whether screening rates varied based on four clinically relevant RLE measures, including comorbidities, in a nationally-representative, community based sample. METHODS: Using the National Social Life, Health and Aging Project (NSHAP), we selected men over 65 without prostate cancer (n=709). They were stratified into three RLE categories (0-7 years, 8-12 years, and 13+ years) based on validated measures of comorbidities, self-rated health status, functional status, and physical performance. The independent relationship of each RLE measure and a combined measure to screening was determined using multivariable logistic regressions. RESULTS: Self-rated health (OR = 6.82; p < 0.01) most closely correlated with RLE-based screening, while the comorbidity index correlated the least (OR = 1.50; p = 0.09). The relationship of RLE to PSA screening significantly strengthened when controlling for the number of doctor visits, particularly for comorbidities (OR= 43.6; p < 0.001). Men who had consistent estimates of less than 7 years RLE by all four measures had an adjusted PSA screening rate of 43.3%. CONCLUSIONS: Regardless of the RLE measure used, men who were estimated to have limited RLE had significant PSA screening rates. However, different RLE measures have different correlations with PSA screening. Specific estimates of over-screening should therefore carefully consider the RLE measure used. PMID- 22773940 TI - Estimation via corrected scores in general semiparametric regression models with error-prone covariates. AB - This paper considers the problem of estimation in a general semiparametric regression model when error-prone covariates are modeled parametrically while covariates measured without error are modeled nonparametrically. To account for the effects of measurement error, we apply a correction to a criterion function. The specific form of the correction proposed allows Monte Carlo simulations in problems for which the direct calculation of a corrected criterion is difficult. Therefore, in contrast to methods that require solving integral equations of possibly multiple dimensions, as in the case of multiple error-prone covariates, we propose methodology which offers a simple implementation. The resulting methods are functional, they make no assumptions about the distribution of the mismeasured covariates. We utilize profile kernel and backfitting estimation methods and derive the asymptotic distribution of the resulting estimators. Through numerical studies we demonstrate the applicability of proposed methods to Poisson, logistic and multivariate Gaussian partially linear models. We show that the performance of our methods is similar to a computationally demanding alternative. Finally, we demonstrate the practical value of our methods when applied to Nevada Test Site (NTS) Thyroid Disease Study data. PMID- 22773939 TI - Visualization of a variety of possible dosimetric outcomes in radiation therapy using dose-volume histogram bands. AB - PURPOSE: Dose-volume histograms (DVH) are the most common tool used in the appraisal of the quality of a clinical treatment plan. However, when delivery uncertainties are present, the DVH may not always accurately describe the dose distribution actually delivered to the patient. We present a method, based on DVH formalism, to visualize the variability in the expected dosimetric outcome of a treatment plan. METHODS: For a case of chordoma of the cervical spine, we compared 2 intensity modulated proton therapy plans. Treatment plan A was optimized based on dosimetric objectives alone (ie, desired target coverage, normal tissue tolerance). Plan B was created employing a published probabilistic optimization method that considered the uncertainties in patient setup and proton range in tissue. Dose distributions and DVH for both plans were calculated for the nominal delivery scenario, as well as for scenarios representing deviations from the nominal setup, and a systematic error in the estimate of range in tissue. The histograms from various scenarios were combined to create DVH bands to illustrate possible deviations from the nominal plan for the expected magnitude of setup and range errors. RESULTS: In the nominal scenario, the DVH from plan A showed superior dose coverage, higher dose homogeneity within the target, and improved sparing of the adjacent critical structure. However, when the dose distributions and DVH from plans A and B were recalculated for different error scenarios (eg, proton range underestimation by 3 mm), the plan quality, reflected by DVH, deteriorated significantly for plan A, while plan B was only minimally affected. In the DVH-band representation, plan A produced wider bands, reflecting its higher vulnerability to delivery errors, and uncertainty in the dosimetric outcome. CONCLUSIONS: The results illustrate that comparison of DVH for the nominal scenario alone does not provide any information about the relative sensitivity of dosimetric outcome to delivery uncertainties. Thus, such comparison may be misleading and may result in the selection of an inferior plan for delivery to a patient. A better-informed decision can be made if additional information about possible dosimetric variability is presented; for example, in the form of DVH bands. PMID- 22773941 TI - MEASURING WORKLOAD OF ICU NURSES WITH A QUESTIONNAIRE SURVEY: THE NASA TASK LOAD INDEX (TLX). AB - High workload of nurses in Intensive Care Units (ICUs) has been identified as a major patient safety and worker stress problem. However, relative little attention has been dedicated to the measurement of workload in healthcare. The objectives of this study are to describe and examine several methods to measure workload of ICU nurses. We then focus on the measurement of ICU nurses' workload using a subjective rating instrument: the NASA TLX.We conducted secondary data analysis on data from two, multi-side, cross-sectional questionnaire studies to examine several instruments to measure ICU nurses' workload. The combined database contains the data from 757 ICU nurses in 8 hospitals and 21 ICUs.Results show that the different methods to measure workload of ICU nurses, such as patient-based and operator-based workload, are only moderately correlated, or not correlated at all. Results show further that among the operator-based instruments, the NASA TLX is the most reliable and valid questionnaire to measure workload and that NASA TLX can be used in a healthcare setting. Managers of hospitals and ICUs can benefit from the results of this research as it provides benchmark data on workload experienced by nurses in a variety of ICUs. PMID- 22773942 TI - Protein Nanospheres: Synergistic Nanoplatform-Based Probes for Multimodality Imaging. AB - No single clinical imaging modality has the ability to provide both high resolution and high sensitivity at the anatomical, functional and molecular level. Synergistically integrated detection techniques overcome these barriers by combining the advantages of different imaging modalities while reducing their disadvantages. We report the development of protein nanospheres optimized for enhancing MRI, CT and US contrast while also providing high sensitivity optical detection. Transferrin protein nanospheres (TfpNS), silicon coated, doped rare earth oxide and rhodamine B isothiocyanate nanoparticles, Si?Gd(2)O(3):Eu,RBITC, (NP) and transferrin protein nanospheres encapsulating Si?Gd(2)O(3):Eu,RBITC nanoparticles (TfpNS-NP) were prepared in tissue-mimicking phantoms and imaged utilizing multiple cross-sectional imaging modalities. Preliminary results indicate a 1:1 NP to TfpNS ratio in TfpNS-NP and improved sensitivity of detection for MRI, CT, US and fluorescence imaging relative to its component parts and/or many commercially available contrast agents. PMID- 22773943 TI - Synthesis of flinderoles B and C by a gold-catalyzed allene hydroarylation(). AB - The recent development of new gold(I) catalysis methodologies has opened the door to new disconnections for the total synthesis of bioactive complex molecules. Below is described the application of a gold(I)-catalyzed hydroarylation of an allene with indole toward the total synthesis of flinderoles B-C, members of a new class of antimalarial bisindole alkaloids isolated from plants of the Flindersia genus. The key gold(I) step establishes both the pyrrolidine and isobutenyl functionalities unique to these compounds. Other important steps of the synthesis include a convergent Horner-Wadsworth-Emmons olefination to construct the bridging alkene and a new strategy for alpha-indole enolate alkylations. PMID- 22773944 TI - The pathophysiology of inhalational brucellosis in BALB/c mice. AB - To characterize the clinical presentation and pathophysiology of inhalational brucellosis, Balb/c mice were challenged with Brucella melitensis 16M in a nose only aerosol exposure chamber. A low dose of 1000 cfu/animal of B. melitensis resulted in 45% of mice with tissue burdens eight weeks post-challenge. The natural history of brucellosis in mice challenged by higher aerosol doses was examined by serial euthanizing mice over an eight week period. Higher challenge doses of 1.00E+05 and 5.00E+05 cfu resulted in positive blood cultures 14 days post-challenge and bacterial burdens were observed in the lung, liver and/or spleens 14 days post-challenge. In addition, the progression of brucellosis was similar between mice challenged by the intranasal and aerosol routes. The results from this study support the use of the Balb/c aerosol nose-only brucellosis mouse model for the evaluation of therapeutics against inhalational brucellosis. PMID- 22773945 TI - T1R3: a human calcium taste receptor. AB - Many animals can detect the taste of calcium but it is unclear how or whether humans have this ability. We show here that calcium activates hTAS1R3-transfected HEK293 cells and that this response is attenuated by lactisole, an inhibitor of hT1R3. Moreover, trained volunteers report that lactisole reduces the calcium intensity of calcium lactate. Thus, humans can detect calcium by taste, T1R3 is a receptor responsible for this, and lactisole can reduce the taste perception of calcium by acting on T1R3. PMID- 22773946 TI - Intersectional Cre driver lines generated using split-intein mediated split-Cre reconstitution. AB - Tissue and cell type highly specific Cre drivers are very rare due to the fact that most genes or promoters used to direct Cre expressions are generally expressed in more than one tissues and/or in multiple cell types. We developed a split-intein based split-Cre system for highly efficient Cre-reconstitution through protein splicing. This split-intein-split-Cre system can be used to intersect the expression patterns of two genes or promoters to restrict full length Cre reconstitution in their overlapping domains. To test this system in vivo, we selected several conserved human enhancers to drive the expression of either Cre-N-intein-N, or intein-C-Cre-C transgene in different brain regions. In all paired CreN/CreC transgenic mice, Cre-dependent reporter was efficiently induced specifically in the intersectional expression domains of two enhancers. This split-intein based method is simpler to implement compared with other strategies for generating highly-restricted intersectional Cre drivers to study complex tissues such as the nervous system. PMID- 22773947 TI - USP11 augments TGFbeta signalling by deubiquitylating ALK5. AB - The TGFbeta receptors signal through phosphorylation and nuclear translocation of SMAD2/3. SMAD7, a transcriptional target of TGFbeta signals, negatively regulates the TGFbeta pathway by recruiting E3 ubiquitin ligases and targeting TGFbeta receptors for ubiquitin-mediated degradation. In this report, we identify a deubiquitylating enzyme USP11 as an interactor of SMAD7. USP11 enhances TGFbeta signalling and can override the negative effects of SMAD7. USP11 interacts with and deubiquitylates the type I TGFbeta receptor (ALK5), resulting in enhanced TGFbeta-induced gene transcription. The deubiquitylase activity of USP11 is required to enhance TGFbeta-induced gene transcription. RNAi-mediated depletion of USP11 results in inhibition of TGFbeta-induced SMAD2/3 phosphorylation and TGFbeta-mediated transcriptional responses. Central to TGFbeta pathway signalling in early embryogenesis and carcinogenesis is TGFbeta-induced epithelial to mesenchymal transition. USP11 depletion results in inhibition of TGFbeta-induced epithelial to mesenchymal transition. PMID- 22773948 TI - Reduced Na(+) and higher K(+) channel expression and function contribute to right ventricular origin of arrhythmias in Scn5a+/- mice. AB - Brugada syndrome (BrS) is associated with ventricular tachycardia originating particularly in the right ventricle (RV). We explore electrophysiological features predisposing to such arrhythmic tendency and their possible RV localization in a heterozygotic Scn5a+/- murine model. Na(v)1.5 mRNA and protein expression were lower in Scn5a+/- than wild-type (WT), with a further reduction in the RV compared with the left ventricle (LV). RVs showed higher expression levels of K(v)4.2, K(v)4.3 and KChIP2 in both Scn5a+/- and WT. Action potential upstroke velocity and maximum Na(+) current (I(Na)) density were correspondingly decreased in Scn5a+/-, with a further reduction in the RV. The voltage dependence of inactivation was shifted to more negative values in Scn5a+/-. These findings are predictive of a localized depolarization abnormality leading to slowed conduction. Persistent Na(+) current (I(pNa)) density was decreased in a similar pattern to I(Na). RV transient outward current (I(to)) density was greater than LV in both WT and Scn5a+/-, and had larger time constants of inactivation. These findings were also consistent with the observation that AP durations were smallest in the RV of Scn5a+/-, fulfilling predictions of an increased heterogeneity of repolarization as an additional possible electrophysiological mechanism for arrhythmogenesis in BrS. PMID- 22773950 TI - Non-invasive prenatal diagnosis by massively parallel sequencing of maternal plasma DNA. AB - The presence of foetal DNA in the plasma of pregnant women has opened up new possibilities for non-invasive prenatal diagnosis. The use of circulating foetal DNA for the non-invasive prenatal detection of foetal chromosomal aneuploidies is challenging as foetal DNA represents a minor fraction of maternal plasma DNA. In 2007, it was shown that single molecule counting methods would allow the detection of the presence of a trisomic foetus, as long as enough molecules were counted. With the advent of massively parallel sequencing, millions or billions of DNA molecules can be readily counted. Using massively parallel sequencing, foetal trisomies 21, 13 and 18 have been detected from maternal plasma. Recently, large-scale clinical studies have validated the robustness of this approach for the prenatal detection of foetal chromosomal aneuploidies. A proof-of-concept study has also shown that a genome-wide genetic and mutational map of a foetus can be constructed from the maternal plasma DNA sequencing data. These developments suggest that the analysis of foetal DNA in maternal plasma would play an increasingly important role in future obstetrics practice. It is thus a priority that the ethical, social and legal issues regarding this technology be systematically studied. PMID- 22773949 TI - Insights into the roles of local translation from the axonal transcriptome. AB - Much of our knowledge on the roles of intra-axonal translation derives from the characterization of a small number of individual mRNAs that were found to be localized in axons. However, two recent studies, using large-scale approaches to provide a more comprehensive characterization of the axonal transcriptome, have led to the discovery of thousands of axonal mRNAs. The apparent abundance of mRNAs in axons raises the possibility that local translation has many more functions than previously thought. Here, we review the recent studies that have profiled axonal mRNAs and discuss how the identification of axonal transcripts might point to unappreciated roles for local translation in axons. PMID- 22773951 TI - Experimental approaches for addressing fundamental biological questions in living, functioning cells with single molecule precision. AB - In recent years, single molecule experimentation has allowed researchers to observe biological processes at the sensitivity level of single molecules in actual functioning, living cells, thereby allowing us to observe the molecular basis of the key mechanistic processes in question in a very direct way, rather than inferring these from ensemble average data gained from traditional molecular and biochemical techniques. In this short review, we demonstrate the impact that the application of single molecule bioscience experimentation has had on our understanding of various cellular systems and processes, and the potential that this approach has for the future to really address very challenging and fundamental questions in the life sciences. PMID- 22773952 TI - Regulation of ASIC channels by a stomatin/STOML3 complex located in a mobile vesicle pool in sensory neurons. AB - A complex of stomatin-family proteins and acid-sensing (proton-gated) ion channel (ASIC) family members participate in sensory transduction in invertebrates and vertebrates. Here, we have examined the role of the stomatin-family protein stomatin-like protein-3 (STOML3) in this process. We demonstrate that STOML3 interacts with stomatin and ASIC subunits and that this occurs in a highly mobile vesicle pool in dorsal root ganglia (DRG) neurons and Chinese hamster ovary cells. We identify a hydrophobic region in the N-terminus of STOML3 that is required for vesicular localization of STOML3 and regulates physical and functional interaction with ASICs. We further characterize STOML3-containing vesicles in DRG neurons and show that they are Rab11-positive, but not part of the early-endosomal, lysosomal or Rab14-dependent biosynthetic compartment. Moreover, uncoupling of vesicles from microtubules leads to incorporation of STOML3 into the plasma membrane and increased acid-gated currents. Thus, STOML3 defines a vesicle pool in which it associates with molecules that have critical roles in sensory transduction. We suggest that the molecular features of this vesicular pool may be characteristic of a 'transducosome' in sensory neurons. PMID- 22773953 TI - Ethical Discourse about the Modification of Food for Therapeutic Purposes: How Patients with Gastrointestinal Diseases View the Good, the Bad, and the Healthy. AB - BACKGROUND: Researchers have the potential to utilize genetic modification (GM) technologies to create a hybrid of "food" and "medicine" that may challenge traditional understandings of what is "natural". Moral and ethical concerns are likely to arise in any discussion of these therapeutic foods and will affect the integration of products into clinical care and daily life. This study examined how patients with chronic gastrointestinal (GI) diseases view probiotics as future bioengineered therapeutic foods. METHODS: A multi-site qualitative study consisting of focus groups with chronic GI diseases was conducted at Cleveland Clinic, Mayo Clinic, and Johns Hopkins University RESULTS: We conducted twenty two focus groups with 136 patients with major GI diseases between March and August 2009. GI patients associated the term "natural" with concepts of diminished risk and morally "good"; conversely, patients associated the term "unnatural" with things that are "risky," "foreign", and morally "bad". Readily available unmodified probiotics were more commonly described as "natural" while genetically modified probiotics were more commonly labeled as "unnatural" and "risky". However, patients acknowledged that not all natural products are safe, nor are unnatural products always harmful. CONCLUSIONS: If GI patient perspectives are indicative of public perceptions of therapeutic foods, our findings suggest that the potential benefits and risks of clinical and public health initiatives employing therapeutic foods will be understood in moralistic terms. Bioethicists and others should be sensitive to the implicit normative appeals that are often embedded in the language of what is "natural" and "unnatural". PMID- 22773954 TI - Epithelial-mesenchymal transition, the tumor microenvironment, and metastatic behavior of epithelial malignancies. AB - OBJECTIVE: The mechanisms of cancer metastasis have been intensely studied recently and may provide vital therapeutic targets for metastasis prevention. We sought to review the contribution of epithelial-mesenchymal transition and the tumor microenvironment to cancer metastasis. SUMMARY BACKGROUND DATA: Epithelial mesenchymal transition is the process by which epithelial cells lose cell-cell junctions and baso-apical polarity and acquire plasticity, mobility, invasive capacity, stemlike characteristics, and resistance to apoptosis. This cell biology program is active in embryology, wound healing, and pathologically in cancer metastasis, and along with the mechanical and cellular components of the tumor microenvironment, provides critical impetus for epithelial malignancies to acquire metastatic capability. METHODS: A literature review was performed using PubMed for "epithelial-mesenchymal transition", "tumor microenvironment", "TGF beta and cancer", "Wnt and epithelial-mesenchymal transition", "Notch and epithelial-mesenchymal transition", "Hedgehog and epithelial-mesenchymal transition" and "hypoxia and metastasis". Relevant primary studies and review articles were assessed. RESULTS: Major signaling pathways involved in epithelial mesenchymal transition include TGF-beta, Wnt, Notch, Hedgehog, and others. These pathways converge on several transcription factors, including zinc finger proteins Snail and Slug, Twist, ZEB 1/2, and Smads. These factors interact with one another and others to provide crosstalk between the relevant signaling pathways. MicroRNA suppression and epigenetic changes also influence the changes involved in epithelial-mesenchymal transition. Cellular and mechanical components of the tumor microenvironment are also critical in determining metastatic potential. CONCLUSIONS: While the mechanisms promoting metastasis are extremely wide ranging and still under intense investigation, the epithelial-mesenchymal transition program and the tumor microenvironment are both critically involved in the acquisition of metastatic potential. As our understanding of these complexities increases, the ability to target these processes for therapy will offer new promise in the treatment of epithelial malignancy and metastasis. PMID- 22773955 TI - The CRM1 nuclear export protein in normal development and disease. AB - CRM1 (Chromosomal Maintenance 1, also known as Exportin 1) is the major mammalian export protein that facilitates the transport of large macromolecules including RNA and protein across the nuclear membrane to the cytoplasm. The gene encoding CRM1 was originally identified in yeast as required to maintain higher order chromosome structure. In mammalian cells, CRM1 was found to bind several nuclear pore proteins hence its role in nuclear-cytosolic transport was discovered. In addition to nuclear-cytosolic transport, CRM1 also plays a role in centrosome duplication and spindle assembly, especially in response to DNA damage. The crystal structure of CRM1 suggests a complex protein that binds the Ran protein bound to GTP, allowing for a conformational change that facilitates binding to different cargo proteins through a nuclear export signal (NES). Included in the cadre of cargo are multiple tumor suppressor and oncoproteins as p53, BRCA1, Survivin, NPM, and APC, which function in the nucleus to regulate transcription or aid in chromosomal assembly and movement. An imbalance in the cytosolic level of these proteins has been observed in cancer cells, resulting in either inactivation (tumor suppressor) or an excess of anti-apoptotic activity (oncoprotein). Thus, the concept of inhibiting CRM1 has been explored as a potential therapeutic intervention. Indeed, inhibition of CRM1 by a variety of small molecules that interfere with cargo-NES binding results in cancer cell death. Whether all of these proteins together are responsible for this phenotype or whether specific proteins are required for this effect is unclear at this time. PMID- 22773956 TI - 14-3-3 proteins in neurological disorders. AB - 14-3-3 proteins were originally discovered as a family of proteins that are highly expressed in the brain. Through interactions with a multitude of binding partners, 14-3-3 proteins impact many aspects of brain function including neural signaling, neuronal development and neuroprotection. Although much remains to be learned and understood, 14-3-3 proteins have been implicated in a variety of neurological disorders based on evidence from both clinical and laboratory studies. Here we will review previous and more recent research that has helped us understand the roles of 14-3-3 proteins in both neurodegenerative and neuropsychiatric diseases. PMID- 22773958 TI - Suppression of survivin promoter activity by YM155 involves disruption of Sp1-DNA interaction in the survivin core promoter. AB - YM155, a novel survivin suppressant, shows potent antitumor activity against various human cancers and is currently in phase II clinical trials. In this study, we investigated whether YM155 selectively inhibits survivin transcription. We hypothesize that inhibition of survivin transcription plays a role in YM155 mediated survivin inhibition. We found that YM155 inhibited survivin promoter activity, while it showed minimal inhibitory effect on four control gene promoters in transfection and luciferase activity assay experiments, indicating its selectivity. Transfection of various survivin promoter-luciferase constructs followed by luciferase assays revealed that the survivin core promoter (269 bp) plays a major role in YM155-mediated inhibitory effects. However, flow cytometry analysis indicated that inhibition of survivin promoter activity by YM155 is cell cycle-independent without G1 cell arrests. Electrophoretic mobility shift assays (EMSA) identified that YM155 abrogates nuclear proteins binding to the region of 149 to -71, in which Sp1 is a major candidate, and that YM155 treatment induces Sp1 re-subcellular localization without inhibiting its expression. Forced expression of Sp1 neutralized YM155-mediated downregulation of survivin promoter activity. Consistently, mutation of the identified Sp1 sites in the oligonucleotide probe diminished DNA-protein interactions in EMSA experiments, and mutation of the Sp1 sites in the survivin promoter-luciferase construct diminished survivin promoter activity. These findings indicate that YM155 inhibition of survivin expression is at least in part through its inhibition of survivin transcription by disruption of Sp1 interaction with the region of -149 to -71 in the survivin core promoter. PMID- 22773957 TI - Targeted genes and interacting proteins of hypoxia inducible factor-1. AB - Heterodimeric transcription factor hypoxia inducible factor-1 (HIF-1) functions as a master regulator of oxygen homeostasis in almost all nucleated mammalian cells. The fundamental process adapted to cellular oxygen alteration largely depends on the refined regulation on its alpha subunit, HIF-1alpha. Recent studies have unraveled expanding and critical roles of HIF-1alpha, involving in a multitude of developmental, physiological, and pathophysiological processes. This review will focus on the current knowledge of HIF-1alpha-targeting genes and its interacting proteins, as well as the concomitant functional relationships between them. PMID- 22773960 TI - Site-directed mutagenesis of a family 42 beta-galactosidase from an antarctic bacterium. AB - Site directed mutagenesis was used to modify the active site of a cold active beta-galactosidase taken from an Antarctic psychrotolerant Planococcus Bacterial isolate. The goal was to modify the active site such that there would be an increase in activity on certain substrates which showed little to no activity with the wild type enzyme. A total of 5 mutant enzymes were constructed with amino acid changes based on an analysis done via homology modeling. All 5 modified enzymes were assayed using 14 different nitrophenol substrates. In most cases there was a loss of activity on substrates that showed activity with the wild type enzymes. None of the expected activity was observed with any of the mutants, possibly in part due to a decrease in hydrogen bonding between the active site and the substrates. With the substrates p-nitrophenyl-beta-d galacturonide and p-nitrophenyl-alpha-d-glucopyranoside we saw increased activity. With one of the mutants we measured a 320% increase in activity on p nitrophenyl-beta-d-galacturonide. Two other mutants showed activity on p nitrophenyl-alpha-d-glucopyranoside, which showed no activity at all with the wild type enzyme. PMID- 22773959 TI - BAR proteins in cancer and blood disorders. AB - Remodeling of the membrane and cytoskeleton is involved in a wide range of normal and pathologic cellular function. These are complex, highly-coordinated biochemical and biophysical processes involving dozens of proteins. Serving as a scaffold for a variety of proteins and possessing a domain that interacts with plasma membranes, the BAR family of proteins contribute to a range of cellular functions characterized by membrane and cytoskeletal remodeling. There are several subgroups of BAR proteins: BAR, N-BAR, I-BAR, and F-BAR. They differ in their ability to induce angles of membrane curvature and in their recruitment of effector proteins. Evidence is accumulating that BAR proteins contribute to cancer cell invasion, T cell trafficking, phagocytosis, and platelet production. In this review, we discuss the physiological function of BAR proteins and discuss how they contribute to blood and cancer disorders. PMID- 22773961 TI - Gastrodia elata Blume (tianma) mobilizes neuro-protective capacities. AB - Tianma (Gastrodia elata Blume) is a traditional Chinese medicine (TCM) often used for the treatment of headache, convulsions, hypertension and neurodegenerative diseases. Tianma also modulates the cleavage of the amyloid precursor protein App and cognitive functions in mice. The neuronal actions of tianma thus led us to investigate its specific effects on neuronal signalling. Accordingly, this pilot study was designed to examine the effects of tianma on the proteome metabolism in differentiated mouse neuronal N2a cells using an iTRAQ (isobaric tags for relative and absolute quantitation)-based proteomics research approach. We identified 2178 proteins, out of which 74 were found to be altered upon tianma treatment in differentiated mouse neuronal N2a cells. Based on the observed data obtained, we hypothesize that tianma could promote neuro-regenerative processes by inhibiting stress-related proteins and mobilizing neuroprotective genes such as Nxn, Dbnl, Mobkl3, Clic4, Mki67 and Bax with various regenerative modalities and capacities related to neuro-synaptic plasticity. PMID- 22773962 TI - Short-term and long-term effects of protein kinase C on the trafficking and stability of human organic anion transporter 3. AB - Human organic anion transporter 3 (hOAT3) belongs to a family of organic anion transporters that play critical roles in the body disposition of numerous clinically important drugs. Therefore, understanding the regulation of this transporter has profound clinical significance. In the current study, we investigated the short-term and long-term regulation of hOAT3 by protein kinase C (PKC). We showed that short-term activation of PKC by phobol 12-Myristate 13 Acetate (PMA) inhibited hOAT3 activity through accelerating its internalization from cell surface to intracellular recycling endosomes. The colocalization of hOAT3 with EEA1-positive recycling endosomes was demonstrated by immunolocalization with confocal microscopy. Furthermore, we showed that long term activation of PKC resulted in the enhanced degradation of cell surface hOAT3. The pathways for hOAT3 degradation were further examined using proteasomal and lysosomal inhibitors. Our results showed that both proteasomal inhibitors and the lysosomal inhibitors significantly blocked hOAT3 degradation. These results demonstrate that PKC plays critical roles in the trafficking and the stability of hOAT3. PMID- 22773964 TI - A motor-driven mechanism for cell-length sensing. AB - Size homeostasis is fundamental in cell biology, but it is not clear how large cells such as neurons can assess their own size or length. We examined a role for molecular motors in intracellular length sensing.Computational simulations suggest that spatial information can be encoded by the frequency of an oscillating retrograde signal arising from a composite negative feedback loop between bidirectional motor-dependent signals. The model predicts that decreasing either or both anterograde or retrograde signals should increase cell length, and this prediction was confirmed upon application of siRNAs for specific kinesin and/or dynein heavy chains in adult sensory neurons. Heterozygous dynein heavy chain 1 mutant sensory neurons also exhibited increased lengths both in vitro and during embryonic development.Moreover, similar length increases were observed in mouse embryonic fibroblasts upon partial downregulation of dynein heavy chain 1.Thus, molecular motors critically influence cell length sensing and growth control. PMID- 22773963 TI - The primate thalamostriatal systems: Anatomical organization, functional roles and possible involvement in Parkinson's disease. AB - The striatum receives glutamatergic inputs from two main thalamostriatal systems that originate either from the centre median/parafascicular complex (CM/PF striatal system) or the rostral intralaminar, midline, associative and relay thalamic nuclei (non-CM/PF-striatal system). These dual thalamostriatal systems display striking differences in their anatomical and, most likely, functional organization. The CM/PF-striatal system is topographically organized, and integrated within functionally segregated basal ganglia-thalamostriatal circuits that process sensorimotor, associative and limbic information. CM/PF neurons are highly responsive to attention-related sensory stimuli, suggesting that the CM/PF striatal system, through its strong connections with cholinergic interneurons, may play a role in basal ganglia-mediated learning, behavioral switching and reinforcement. In light of evidence for prominent CM/PF neuronal loss in Parkinson's disease, we propose that the significant CM-striatal system degeneration, combined with the severe nigrostriatal dopamine loss in sensorimotor striatal regions, may alter normal automatic actions, and shift the processing of basal ganglia-thalamocortical motor programs towards goal-directed behaviors. PMID- 22773966 TI - Towards fast and accurate temperature mapping with proton resonance frequency based MR thermometry. AB - The capability to image temperature is a very attractive feature of MRI and has been actively exploited for guiding minimally-invasive thermal therapies. Among many MR-based temperature-sensitive approaches, proton resonance frequency (PRF) thermometry provides the advantage of excellent linearity of signal with temperature over a large temperature range. Furthermore, the PRF shift has been shown to be fairly independent of tissue type and thermal history. For these reasons, PRF method has evolved into the most widely used MR-based thermometry method. In the present paper, the basic principles of PRF-based temperature mapping will be reviewed, along with associated pulse sequence designs. Technical advancements aimed at increasing the imaging speed and/or temperature accuracy of PRF-based thermometry sequences, such as image acceleration, fat suppression, reduced field-of-view imaging, as well as motion tracking and correction, will be discussed. The development of accurate MR thermometry methods applicable to moving organs with non-negligible fat content represents a very challenging goal, but recent developments suggest that this goal may be achieved. If so, MR-guided thermal therapies may be expected to play an increasingly-important therapeutic and palliative role, as a minimally-invasive alternative to surgery. PMID- 22773965 TI - Degrees of chloroquine resistance in Plasmodium - is the redox system involved? AB - Chloroquine (CQ) was once a very effective antimalarial drug that, at its peak, was consumed in the hundreds of millions of doses per year. The drug acts against the Plasmodium parasite during the asexual intraerythrocytic phase of its lifecycle. Unfortunately, clinical resistance to this drug is now widespread. Questions remain about precisely how CQ kills malaria parasites, and by what means some CQ-resistant (CQR) parasites can withstand much higher concentrations of the drug than others that also fall in the CQR category. In this review we investigate the evidence for and against the proposal that CQ kills parasites by generating oxidative stress. Further, we examine a long-held idea that the glutathione system of malaria parasites plays a role in CQ resistance. We conclude that there is strong evidence that glutathione levels modulate CQ response in the rodent malaria species P. berghei, but that a role for redox in contributing to the degree of CQ resistance in species infectious to humans has not been firmly established. PMID- 22773967 TI - Future perspectives of prostate cancer therapy. AB - We summarize several recent laboratory advances to tackle the problem of tumor stroma-immune cell microenvironment interaction with the hope of developing and advancing new concepts and therapeutic strategies for prostate cancer therapy by improving bone and soft tissue metastases in prostate cancer patients. Given the emerging enthusiasm for immunotherapy in prostate cancer due to (I) improved understanding of the role of immune cells in the tumor microenvironment, (II) approval by the FDA of an immunotherapeutic drug to treat prostate cancer, and (III) recognition of immunotherapy as a novel approach to treat solid tumors by the Nobel Prize Committee (for discovery of dendritic cells that are used in immunotherapy), the field of tumor immunology is poised for growth in the next decade with the hope of developing new immunomodulatory drugs which will compliment and perhaps eventually replace traditional chemotherapeutic drugs. In this article, we provide a timely review of recent advances in the field of immunotherapy for prostate cancer, lessons learned from successes and failures, the contributory factors in the tumor microenvironment that could be rendered hostile to cancer cells, an exciting area of future research. PMID- 22773968 TI - Inhibitory effect of CCR3 signal on alkali-induced corneal neovascularization. AB - AIM: To investigate the effect of CC chemokine receptor 3 (CCR3) signal on corneal neovascularization (CRNV) induced by alkali burn and to explore its mechanism. METHODS: Specific pathogen-free male BALB/C mice (aged 6-8 weeks) were randomly divided into CCR3-antagonist treated group (experimental group) and control group. CRNV was induced by alkali burn in mice. The time kinetic CCR3 expression in injured corneas was examined by reverse transcription polymerase chain reaction (RT-PCR). CCR3-antagonist (SB-328437 at different concentration of 125ug/mL, 250ug/mL, and 500ug/mL) was locally administrated after alkali injury. The formation of CRNV was assessed by CD31 corneal whole mount staining at two weeks after injury. Monocyte chemotactic protein 1 (MCP-1), monocyte chemotactic protein 3 (MCP-3) expressions in the early phase after injury were quantified and compared by RT-PCR. Macrophage intracorneal accumulation in the early phase after injury was evaluated and compared by immunohistochemistry. RESULTS: Alkali injury induced the time kinetic intracorneal CCR3 expression. 500ug/mL of CCR3 antagonist treatment in the early phase but not the late phase resulted in significant impaired CRNV as compared to control group (P<0.05). CCR3-antagonist treatment in the early phase significantly reduced the intracorneal MCP-1 and MCP 3 enhancement compare to control group at day 2 and day 4 (P<0.05). Moreover, the number of intracorneal macrophage infiltration in the experimental group was reduced than those in control group at day 4 (P<0.05). CONCLUSION: CCR3 signal is involved in alkali-induced CRNV. CCR3-antagonist can inhibit alkali-induced CRNV by reducing the intracorneal MCP-1 and MCP-3 mRNA expression and the intracorneal macrophage infiltration. PMID- 22773969 TI - External sclerostomy with the femtosecond laser versus a surgical knife in rabbits. AB - AIM: To experimentally compare the external sclerostomy produced using a femtosecond laser with that made by a surgical knife and to evaluate the healing patterns, efficacy and technical advantages of femtosecond laser sclerostomy. METHODS: In a prospective randomized, controlled, masked-observer study, 10 pigmented rabbits underwent external sclerostomy with a femtosecond laser in the right eye; 10 additional rabbits underwent sclerostomy with a surgical superblade in the right eye. Clinical characteristics, which included bleb morphology and intraocular pressure, were recorded for 1 month after surgery. Six additional rabbits underwent external femtosecond laser sclerostomy in the right eye and mechanical sclerostomy in the left eye and were killed at day 14 after surgery. Histologic staining, immunohistochemistry and scanning electron microscopy were subsequently performed to assess the morphology of the filtering fistula. The titanium-sapphire femtosecond laboratory laser was operating at a repetition rate of 1 kHz, 0.4 mJ pulse energy, a central wavelength of 800nm and a pulse duration of 50 femtoseconds. Mann-Whitney and Kaplan-Meier tests were used for statistical analysis. RESULTS: Successful complete sclerostomy was achieved in each laser treated eye which was hit only once by the laser. The laser treated time was approximately 15s-16s. In the laser-treated group (n=16), 2 eyes (12%) developed mild hyphema at the site of entry and 8 eyes (50%) showed transient edema in the corneal periphery adjacent to the laser impact zone. The differences between the groups in duration of function blebs and pressure reduction were statistically significant (P=0.025 and 0.016, respectively). The success rate of the laser treated group was significantly higher than the knife group (P=0.005). Histologically, the subconjunctival connective tissue was loosely arranged with partially patent sclerostomy in the laser-treated eyes at postoperative day 14. This contrasted with the completely scarred sclerostomy tract in the knife group. The mean numbers of fibroblasts and new vessels as well as the amount of new collagen deposition at bleb site were significantly decreased in the laser group (P=0.045, 0.013 and 0.036, respectively). CONCLUSION: The current study demonstrates that external femtosecond laser sclerostomy may offer a safe and effective alternative for the minimally invasive surgical management of glaucoma. PMID- 22773970 TI - Effect of brain-derived neurotrophic factor on c-jun expression in the rd mouse retina. AB - AIM: To determine the location of c-jun protein, dynamic changes in c-jun mRNA and protein expression, and ultrastructure characteristics in the rd mouse retina, following a single dose of brain-derived neurotrophic factor (BDNF) in a short period of time. METHODS: A single intravitreal injection of BDNF at two dosages (25ug/L or 50ug/L) was given to the right eye of the rd mouse at age 2 and 3 weeks respectively. Two weeks after injection, the location of c-jun protein in the retina was observed by immunofluorescence detection, c-jun mRNA and protein expression in retinas were detected by quantitative real time polymerase chain reaction (RT-PCR) and western immunoblotting analysis, ultrastructure characteristics of retinas were detected by transmission electron microscope (TEM) observation. RESULTS: c-jun protein was expressed in the inner nuclear layer (INL) of retina. BDNF at two dosages (25ug/L and 50ug/L) increased c-jun mRNA expression at PN-4 weeks respectively (P(1)=0.019, P(2)=0.021). 50ug/L BDNF increased c-jun protein expression at PN-4 weeks (P =0.000). The retinal ultrastructure was improved. CONCLUSION: The effects of BDNF exerts on the c-jun expression in the retina are dose-dependent and time-dependent, which may mediate photoreceptor rescue indirectly in the pathological process of retinitis pigmentosa (RP) at early stage. PMID- 22773971 TI - Effects of salvianolic acid B on in vitro growth inhibition and apoptosis induction of retinoblastoma cells. AB - AIM: To observe the effects of salvianolic acid B (SalB) on in vitro growth inhibition and apoptosis induction of retinoblastoma HXO-RB44 cells. METHODS: The effects of SalB on the HXO-RB44 cells proliferation in vitro were observed by MTT colorimetric method. The morphological changes of apoptosis before and after the treatment of SalB were observed by Hoechst 33258 fluorescent staining method. Apoptosis rate and cell cycle changes of HXO-RB44 cells were detected by flow cytometer at 48 hours after treated by SalB. The expression changes of Caspase-3 protein in HXO-RB44 cells were detected by Western Blot. RESULTS: SalB significantly inhibited the growth of HXO-RB44 cells, while the inhibition was in a concentration-and time-dependent manner. The results of fluorescent staining method indicated that HXO-RB44 cells showed significant phenomenon of apoptosis including karyorrhexis, fragmentation and the formation of apoptotic bodies, etc. after 24, 48 and 72 hours co-culturing of SalB and HXO-RB44 cells. The results of flow cytometer showed that the apoptosis rate and the proportion of cells in S phase were gradually increased at 48 hours and 72 hours after treated by different concentrations of SalB. Western Blot strip showed that the expression of Caspase-3 protein in HXO-RB44 cells was gradually increased with the increase of the concentration of SalB. CONCLUSION: SalB can significantly affect on HXO RB44 cells growth inhibition and apoptosis induction which may be achieved through the up-regulation of Caspase-3 expression and the induction of cell cycle arrest. PMID- 22773972 TI - Experimental Tibetan monkey domestication and its application for intraocular pressure measurement. AB - AIM: To train Tibetan monkey (Macaca thibetana) for intraocular pressure (IOP) measurement in conscious state and obtain normal IOP in conscious Tibetan Macaque. METHODS: The training was based on award-conditioned behavior. Food stimulation and human-animal interaction were used in this training. RESULTS: Trained Tibetan monkeys calmly accepted IOP measurement by the TonoVet(r) rebound tonometer without sedation or anesthesia and their IOP values were similar to other primates. CONCLUSION: Human-cultivated Thibetan monkeys are tamable, and can be used for biomedical research such as ophthalmic research without anesthesia. PMID- 22773973 TI - In vitro reconstruction and characterization of tissue-engineered human corneal epithelium with seeder cells from an untransfected human corneal epithelial cell line. AB - AIM: To demonstrate the morphology and structure of in vitro reconstructed tissue engineered human corneal epithelium (TE-HCEP) with seeder cells from an untransfected HCEP cell line. METHODS: The TE-HCEPs were reconstructed in vitro with seeder cells from an untransfected HCEP cell line, and scaffold carriers of denuded amniotic membrane (dAM) in air-liquid interface culture for 3, 5, 7 and 9 days, respectively. The specimens were examined with hematoxylin-eosin (HE) staining of paraffin-section, immunocytochemical staining, scanning and transmission electron microscopy. RESULTS: During in vitro reconstruction of TE HCEP, HCEP cells formed a 3-4, 6-7 and 8-10 layers of an HCEP-like structure on dAMs in air-liquid interface culture for 3, 5 and 7 days, respectively. But the cells deceased to 5-6 layers and the structure of straified epithelium became loose at day 9. And the cells maintained positive expression of marker proteins (keratin 3 and keratin 12), cell-junction proteins (zonula occludens-1, E cadherin, connexin 43 and integrin beta1) and membrane transport protein of Na(+) K(+) ATPase. The HCEP cells in TE-HCEP were rich in microvilli on apical surface and established numerous cell-cell and cell-dAM junctions at day 5. CONCLUSION: The morphology and structure of the reconstructed TE-HCEP were similar to those of HCEP in vivo. The HCEP cells in the reconstructed TE-HCEP maintained the properties of HCEP cells, including abilities of forming intercellular and cell extracellular matrix junctions and abilities of performing membrane transportation. The untransfected HCEP cells and dAMs could promisingly be used in reconstruction HCEP equivalent for clinical corneal epithelium transplantation. PMID- 22773974 TI - Establishment of an untransfected human corneal stromal cell line and its biocompatibility to acellular porcine corneal stroma. AB - AIM: To establish an untransfected human corneal stromal (HCS) cell line and characterize its biocompatibility to acellular porcine corneal stroma (aPCS). METHODS: Primary culture was initiated with a pure population of HCS cells in DMEM/F12 media (pH 7.2) containing 20% fetal bovine serum and various necessary growth factors. The established cell line was characterized by growth property, chromosome analysis, tumorigenicity assay, expression of marker proteins and functional proteins. Furthermore, the biocompatibility of HCS cells with aPCS was examined through histological and immunocytochemistry analyses and with light, electron microscopies. RESULTS: HCS cells proliferated to confluence 2 weeks later in primary culture and have been subcultured to passage 140 so far. A continuous untransfected HCS cell line with a population doubling time of 41.44 hours at passage 80 has been determined. Results of chromosome analysis, morphology, combined with the results of expression of marker protein and functional proteins suggested that the cells retained HCS cell properties. Furthermore, HCS cells have no tumorigenicity, and with excellent biocompatibility to aPCS. CONCLUSION: An untransfected and non-tumorigenic HCS cell line has been established, and the cells maintained positive expression of marker proteins and functional proteins. The cell line, with excellent biocompatibility to aPCS, might be used for in vitro reconstruction of tissue engineered HCS. PMID- 22773975 TI - Expressions of survivin and vascular endothelial growth factor in a Murine model of proliferative retinopathy. AB - AIM: To examine the expression of survivin and vascular endothelial growth factor(VEGF) during the development of retinal neovascularization (NV) in a mouse model. METHODS: A well-characterized murine model of retinal NV was used to study the expression of survivin and VEGF. NV of the retina was induced in mice by exposure to 75% O(2) from postnatal day P7 to P12, followed by return to room air from P12 to P17. Expression of survivin and VEGF protein was analyzed by Immunohistochemistry. In addition, mouse model of proliferative retinopathy was analyzed by retinal fluorescein angiography and quantification analysis. RESULTS: The normal mice had both superfiekal and deep vascular layers that extended from the optic nerve to the periphery. In intraocular pressure(IOP) mice were characterized by represent a typical pattern of pathological retinal NV. There are less or little nuclei of new vessels vascular endothelial cell breaking through the inner retinal than in retinopathy of prematurity (ROP) mice, large clusters of blood vessels were adherent to the internal limiting membrane(ILM) (0.27+/-0.20 vs 23.38+/-1.027, t=9.454, P<0.001). During the angiogenic period from P13 to P17, survivin and VEGF protein expression increased in experimental retinas compared with control samples(2.56+/-0.46 vs 3.34+/-0.40, t=17.43, P<0.01: 2.18+/-0.75 vs 4.34+/-0.25, t=19.61, P<0.01). Protein levels of VEGF and survivn has significantly positive correlation (P<0.05, r=0.411). CONCLUSION: Correlation was made at the protein levels of survivin expression compared with that of VEGF in a murine model of retinal NV, which suggests a temporal role for survivin and VEGF in new vessel formation in response to hypoxic stimulation. PMID- 22773976 TI - Early expression of surfactant proteins D in Fusarium solani infected rat cornea. AB - AIM: To investigate the early expression of surfactant proteins D(SP-D) in Fusarium solani infected rat cornea. METHODS: Wistar rats were divided into group A, B and C randomly. The right eyes were chosen as the experiment one. Group A was control group. Group B was not inoculated with Fusarium solani. Group C was taken as fusarium solani keratitis model. Five rats in group B and C were executed randomly at 6, 12, 24, 48 and 96 hours respectively after the experimental model being established. The expression of SP-D was assessed through immunohistochemistry and reverse transcription polymerase chain reaction(RT-PCR). RESULTS: RT-PCR detected that the SP-D mRNA expression was low in the corneal of normal rats and group B. The expression of fungal infected cornea increased gradually and reached the peak at 24 hours in group C. The synchronous expression of group B and C were in significant difference (P<0.01). Immunohistochemisty discovered the protein of SP-D expression was increased gradually from 12 hours and reached the peak at 48 hours in group C. The synchronous expression of group B and C were also in significant difference (P<0.01). CONCLUSION: There exists SP D in rat corneal tissue and the expression is significantly increased at the early period of fusarium solani infected cornea. SP-D may play a role in the early innate immunity response of the corneal resistance to Fusarium solani infection. PMID- 22773977 TI - TGFBI and CHST6 gene analysis in Chinese stromal corneal dystrophies. AB - AIM: To investigate whether mutations in TGFBI gene or CHST6 gene correlated with stromal corneal dystrophies (CD) in 8 Chinese probands. METHODS: Eight unrelated patients with stromal corneal dystrophies were recruited in this study; all affected members were assessed by completely ophthalmologic examinations. Genomic DNA was extracted from peripheral leukocytes, 17 exons of TGFBI gene and the exon of CHST6 gene were amplified by polymerase chain reaction (PCR), sequenced directly and compared with the reference database. RESULTS: Three heterozygous mutations in TGFBI gene were identified in six patients: c. 370C>T (p.Arg124Cys) was found in exon 4 of TGFBI gene in three members, c. 371G>A (p.Arg124His) was found in one patient; c. 1663C>T (p.Arg555Trp) was found in exon 12 in other two members. In addition, four polymorphisms with the nucleotide changes rs1442, rs1054124, rs4669, and rs35151677 were found in TGFBI gene. Mutations were not identified in the rest of 2 affected individuals in TGFBI gene or CHST6 gene. CONCLUSION: Within these patients, R124C, R124H and R555W mutations were co segregated with the disease phenotypes and were specific mutations for lattice corneal dystrophy type I (LCD I), Avellino corneal dystrophy (ACD, GCD II), granular corneal dystrophy type I (GCD I), respectively. Our study highlights the prevalence of codon 124 and codon 555 mutations in the TGFBI gene among the Chinese stromal corneal dystrophies patients. PMID- 22773978 TI - Transforming growth factor-beta neutralizing antibodies inhibit subretinal fibrosis in a mouse model. AB - AIM: To determine the involvement of the transforming growth factor (TGF)-beta with the development of experimental subretinal fibrosis in a mouse model. METHODS: Subretinal fibrosis was induced by subretinal injection of macrophage rich peritoneal exudate cells (PECs) and the local expression of TGF-beta isoforms was assessed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at various time points. In addition, we investigated the effect of TFG-beta-neutralizing antibodies (TGF-beta NAb) on subretinal fibrosis development. RESULTS: TGF-beta1 and TGF-beta2 mRNA level was significantly elevated at day 2 after subretinal fibrosis induction and increased further to 5 and 6.5-fold respectively at day 5, reaching the peak. TGF-beta3 mRNA was not detected in the present study. The result of ELSIA showed that active TGF-beta1 and TGF-beta2 levels were upregulated to 10-fold approximately, while total TGF-beta1 and TGF-beta2 levels were even upregulated more than 10-fold and more than 20-fold respectively in subretinal fibrosis mice in comparison with naive mice at day 5. TGF-beta NAb resulted in a reduced subretinal fibrosis areas by 65% compared to animals from control group at day 7. CONCLUSION: Our results indicate that TGF-beta signaling may contribute to the pathogenesis of subretinal fibrogenesis and TGF-beta inhibition may provide an effective, novel treatment of advanced and late-stage neovascular age-related macular degeneration. PMID- 22773979 TI - Relations between lymphangiogenesis and the size of pterygium. AB - AIM: To examine the relations between lymphangiogenesis and the size of pterygium. METHODS: Tissues from 88 primary and 34 recurrent pterygia were evaluated, and those from 7 nasal epibulbar conjunctiva segments were used as controls. Pterygium slices from each patient were stained with LYVE-1 monoclonal antibodies to identify lymphatic microvessel for calculating lymph-vascular area (LVA), lymph-microvascular density (LMD) and lymph-vascular luminal diameter (LVL). Also, the relations between lymphangiogenesis (measuring by LVA, LMD and LVL) and the size of pterygium (extension, width and area) were explored. RESULTS: There were a few LYVE-1((+)) lymphatic vessels in normal epibulbar conjunctiva segments. However, the number of lymphatic vessels slightly increased in primary pterygia and dramatically increased in recurrent pterygia. LVA, LMD and LVL significantly increased in recurrent pterygia in comparison with primary pterygia (all P<0.05). Both LMD and LVA were correlated with the width and area of pterygia (both P< 0.05), and LVA was also correlated with the extension of pterygia(P<0.05). CONCLUSION: Lymphangiogenesis is correlated with the size of pterygium. The outgrowth of lymphatic vessels might contribute to the development of pterygia. PMID- 22773980 TI - Cigarette smoking, body mass index associated with the risks of age-related cataract in male patients in northeast China. AB - AIM: To determine the association between cigarettes smoking, body mass index (BMI) and the risk of age-related cataract (ARC) in middle-aged and elderly men in Northeast China. METHODS: A hospital-based case control study was conducted. Cases (n =362) were men who had surgically treated ARC, 45-85 years old; controls frequency-matched (n =362) were men who had been admitted to the same hospital as cases for other diseases not related with eye diseases. Cases and controls were matched with 1:1. The cases and controls were interviewed during their hospital stay, using a structured interviewer-administrated questionnaire that included information on sociodemographic characteristics, socioeconomic, lifestyle habits (tobacco smoking and alcohol consumption, etc.), anthropometric measures, personal medical history, and family history of ARC in first-degree relatives, and simultaneously BMI was calculated. The odds ratios (OR) and 95% confidence intervals (CI) of ARC were estimated using multiple logistic regression models. RESULTS: After adjusting for age and multiple potential confounders, higher BMI was associated with an increased risk of ARC. Cigarette smoking, years smoking or moderate cigarette smoking (1-29 cigarettes per day) had no relation with the risk of ARC (P>0.05), although patients smoking >=30 cigarettes per day had an elevated risk of ARC as compared with the non-smokers (OR=1.55, 95% CI; 1.16 2.85, P=0.026). Higher BMI was associated with an increased risk of ARC. Both overweight and obesity was associated with an obviously increased risk for surgically ARC (OR=1.55, 95% CI: 1.02-1.98, P=0.015 and OR=1.71, 95% CI: 1.32 2.39, P=0.013 respectively) compared to normal BMI. Then participants were grouped into quartiles of BMI (Q1 to Q4), compared to controls in the lowest quartile, the OR for cases in the highest quartile of BMI was 1.54 (OR=1.54, 95% CI: 1.08-2.46, P=0.022). The results of univariate analysis showed cigarette smoking was not associated with ARC formation for men with lower or normal BMI (P>0.05). Compared to the non-smokers, for men of overweight or obesity, cigarette smoking was associated with a significantly increased risk for surgically ARC (OR=2.00, 95% CI: 1.49-6.65, P=0.003 and OR=1.66, 95% CI: 1.63 13.21, P=0.002 respectively). Similarly, smokers in the highest quartile of BMI had approximately 1.5 times the risk of ARC as non-smokers in the lowest quartile (OR=1.46, 95% CI: 1.06-5.29, P<0.001). Followed multivariate models revealed that the association had never changed. CONCLUSION: Current cigarette smoking is positively related to ARC only among those who smoking 30 or more cigarettes per day. For men who are both overweight and obesity, cigarette smoking is associated with a significantly increased risk for ARC. PMID- 22773981 TI - Visual and optical performance of eyes with different corneal spherical aberration implanted with aspheric intraocular lens. AB - AIM: To compare the visual and optical performance of eyes with different corneal spherical aberration (SA) implanted with spherical aberration-free intraocular lens (IOLs). METHODS: Thirty-six patients with different corneal SA had phacoemulsification with implantation of spherical aberration-free IOLs. Patients were divided into 3 groups according to the value of preoperative corneal SA. Eyes with corneal SA <0.10um were assigned to group A, those with 0.10 <=corneal SA <0.20um to Group B, and those with 0.20<= corneal SA <0.35um to Group C. Best corrected visual acuity (BCVA), contrast sensitivity, corneal SA, total ocular aberrations, and depth of focus were recorded 3 months postoperatively. Distance corrected near and intermediate visual acuity was studied to measure depth of focus. RESULTS: BCVA and contrast sensitivity were similar between groups. There were no significant differences in distance-corrected near or intermediate visual acuity. Corneal SA was similar before and 3 months after surgery in the 3 groups. With a 5.0mm pupil diameter, root mean square values for total ocular higher order aberrations (HOAs) were lower in groups A and B than in group C. Total ocular SA was lower in group A than in groups B and C. SA was also lower in group B than in group C. Coma and trefoil were similar between the groups. CONCLUSION: Implantation of spherical aberration-free IOLs in eyes with different corneal SA results in similar visual performance at BCVA, contrast sensitivity and depth of focus. PMID- 22773983 TI - Transepithelial photorefractive keratectomy mode using SCHWIND-ESIRIS excimer laser: initial clinical results. AB - AIM: To evaluate postoperative pain, uncorrected visual acuity (UCVA), and cornea haze value after transepithelial photorefractive keratectomy (T-PRK) performed with aspherical ablation profile using SCHWIND ESIRIS excimer laser. METHODS: Retrospective case series. Fifty-nice eyes (32 patients) with myopia associated with or without astigmatism underwent phototherapeutic keratectomy (PTK) followed by photorefractive keratectomy (PRK) which performed by Optimized Refractive Keratecomy (ORK)-CAM software based on aspherical ablation profile using SCHWIND ESIRIS excimer laser. Postoperative pain scale was measured on a questionnaire through five levels. Haze was graded by five grades, and UCVA, manifest refraction spherical equivalent (MRSE) were analyzed. RESULTS: Mean pain level was (1.37+/-0.613) (range: 1 to 3), the mean time picking out the soft contact lens was (6.22+/-1.73) days, at 3 months, UCVA was 1.0 for 40 eyes (67.8%), 0.5 for all eyes (100.0%). The UCVA was significantly less than the preoperative best spectacle corrected visual acuity (BSCVA) (t=-2.84, P=0.006), haze value was (0.27+/-0.25), no patients had a haze grade up to 2. Mean MRSE was (0.76+/-0.96) diopter(D) by 3 months. CONCLUSION: The outcomes from this study show that using the SCHWIND ESIRIS aspherical ablation profile for transepithelial PRK has a good visual result. The primary advantage is related to a spherical ablation profile, automatically considers the ablation volume of the stroma and the accurate and smooth removal of the epithelium with PTK. Additional studies are needed to determine long-term outcomes. PMID- 22773982 TI - Repeatability and agreement of CCT measurement in myopia using entacam and ultrasound pachymetry. AB - AIM: To evaluate the repeatability of central corneal thickness (CCT) measurement by entacam, and agreement of CCT measured by Pentacam and ultrasound pachymetry (USP) in Chinese myopia. Thereby investigate the possibility of Pentacam as a substitute for USP in CCT measurement before refractive surgery. The effects of corneal curvature measured by Pentacam on CCT were also evaluated. METHODS: One hundred and forty-eight right eyes of 148 individual with myopia were included in this study. Three successive Pentacam CCT measurements followed by 10 successive ultrasound pachymetry were carried out in the 148 eyes. Mean of CCT taken by each device was calculated for comparison. According to the CCT measured by USP, all the 148 eyes were divided into 3 groups: <520um, 520-560um, >560um. For all eyes and each group the CCT obtained by Pentacam and USP were compared. Anterior corneal curvature of the 148 eyes was also adopted for correlation analysis with CCT obtained by ultrasound pachymetry. In addition, CCT measurement using 60 random selected Scheimpflug images was performed by 3 skilled investigators at different time, and this was repeated for 3 times by a forth investigator to assess repeatability of Pentacam CCT measurement using Scheimpflug images. RESULTS: Intraclass correlation coefficient (ICC) analysis revealed high intraobserver repeatability (ICC=0.994, F=158.60, P<0.001) for CCT measurement by Pentacam. The interobserver (ICC=0.998, F=494.73, P<0.001) and intraobserver (ICC=0.997, F=383.98, P<0.001) repeatability for Pentacam CCT measurements using Scheimpflug images were also excellent. There was high positive correlation between the CCT values measured by Pentacam and ultrasound pachymetry (r=0.963, P<0.001). Bland-altman plots showed that the Pentacam underestimate the CCT by 8.02um compared with ultrasouond pachymetry. The differences between Pentacam and USP increased as the CCT readings by USP increased (Pentacam vs USP: slope=-0.04, P<0.05). The 95% upper and lower limits of agreement between CCT values obtained from the two devices were +9.33um and -25.37um. No significant association could be found between CCT and anterior corneal curvature. CONCLUSION: Inter- and intraobserver variability for CCT measurements by Pentacam was considerably below clinically significant levels. CCT of myopia obtained by Scheimpflug camera, Pentacam, were highly correlated to that by ultrasound pachymetry. However, the values obtained are not directly interchangeable between Pentacam and ultrasound pachymetry as the 95% limits of agreement are relatively wide. Pentacam can be a useful instrument for measuring CCT in candidates to refractive surgery in clinic. PMID- 22773984 TI - Comparisons of morphologic characteristics between thin-flap LASIK and SBK. AB - AIM: To compare the morphologic characteristics between thin-flap laser in situ keratomileusis (LASIK) and Sub-Bowman keratomileusis (SBK), and to evaluate the uniformity of flap and to explore the correlative factors of corneal flap thickness. METHODS: A prospective, randomized, comparative clinical study was performed in Department of Ophthalmology, West Hospital of China, Chengdu, Sichuan Province, China. Totally 59 patients 114 eyes underwent LASIK or SBK to correct myopia, 29 patients 57 eyes underwent SBK, 30 patients 57 eyes underwent LASIK. Anterior optical coherence tomography(OCT) was used to measure corneal flap thickness in all the patients 1 week after surgeries, 16 positions were set to be measured in each eye. Comparisons of flap thickness in each group and between 2 groups were evaluated. Correlative factors of flap thickness were evaluated. RESULTS: Coefficient of variation (CV, s/*%) in SBK group were lesser than that in LASIK group, t test showed there was significant statistical difference between 2 groups(P=0.000). Comparisons of the difference of 2 paired positions(temporal-nasal; superior-inferior) showed there were no significant differences in each group, but between 2 groups, there were statistical significance of value of difference (D-value) of superior and inferior positions between SBK and LASIK group(P=0.036). Linear regression analysis of correlative factors of flap thickness showed there were no statistic significances related to central corneal thickness(CCT)(P=0.060, t=1.921) and corneal curvature(P=0.083, t=1.766). CONCLUSION: SBK is better than LASIK in creating much uniform corneal flap. There was no evidence showing correlations between flap thickness and CCT or corneal curvature. PMID- 22773985 TI - Comparative study of bacterial status from conjunctival sac of the elder Qiang minority and Han people with dry eye in Sichuan, China. AB - AIM: To compare the status of bacteria in the conjunctival sac from the elder Qiang minority and Han people with dry eyes in Sichuan, China. METHODS: Total of 54 elder Qiang people with dry eyes (108 eyes) were examined by cluster sampling. In the similar habitation region of Han people, 80 (160 dry eyes) Han people were analyzed as the control group. The bacteria was separated from the inferior palpebral conjunctiva, then inoculated on blood plate for 48 hours and identified. RESULTS: Totally 24 strains of bacteria were cultured in either Qiang minority or Han c populations with 3 strains of them existed in both ethnic groups. The commonest bacteria in conjunctival sac in two ethnic groups were non pathogenic bacterium. The composition of Corynebacterium in Han people (54.1%) was significantly higher than that in Qiang minority (27.4%) (chi(2)=11.6721, P=0.0006). The percentage of Sphingomonas Paucimobilis in Qiang people was higher than that in Han people (chi(2)=18.6442, P=0.0000). However, there was no significant difference between Qiang minority and Han people either in bacterial positive rate in conjunctival sac, or the composition of bacteria species and strains, or the composition of staphylococcus epidemids between two ethnic populations. CONCLUSION: There was no significant difference of bacterial positive rate in conjunctival sac from the elder of Qiang minority and Han people with dry eye, but the species of bacteria were different. PMID- 22773986 TI - Comparison of choroidal thickness measured by two methods. AB - AIM: To examine the profile of the choroidal thickness (CT) in healthy myopia subjects and emmetropic participants by Heidelberg Eye explore software and Image J software so as to compare the agreement and reproducibility of the two methods. METHODS: Thirty-six study participants (36 eyes) were enrolled in this research. The fovea and parafoveal region (the region of 6mm diameter of the fovea as center) of the images were selected by spectral domain optic coherence tomography (SD-OCT). The choroidal thickness was measured manually by the Heidelberg Eye explore software (version 5.3.3.0, Heidelberg Engineering) with a vertical line and the Image J software with a line vertical to the retinal pigment epithelial layer. The agreement and reproducibility of the two methods were described by the Bland-Altmann analysis. RESULTS: As compared with Heidelberg Eye explore software (39.9186), the repeatability coefficient is lower calculated by Image J software (27.3525). The Bland-Altmann analysis showed that the limits of 95% CI of agreement analysis is -18.437-63.949um and the upper limits of the precision of the 95% CI of agreement is between 16.102 and 111.796um and the lower limits is range from -66.29-21.41um, which reflected a great variations of the difference. CONCLUSION: The repeatability and agreement of measurement implied by Image J software was better than the Heidelberg Eye explore software. The Image J software should be used for measuring the choroidal thickness in future study in China. PMID- 22773987 TI - Comparison of central macular thickness between two spectral-domain optical coherence tomography in elderly non-mydriatic eyes. AB - AIM: To compare central macular thickness (CMT) measurements obtained by two spectral-domain optical coherence tomography (SD-OCT) exams, and to evaluate measurement reproducibility and agreement between these two exams, and to investigate the relationship between CMT and possible influencing factors such as age, sex, eye (OD/OS), and operators in elderly non-mydriatic eyes. METHODS: Seventy-two normal subjects were included. Every subject underwent CMT measurement twice using one of two SD-OCT (OSE-2000, Moptim, Shenzhen, China & 3 D OCT-1000, Topcon, Tokyo, Japan) instruments respectively where we randomly chose one eye in each patient for the test; these exams were performed by two operators over an hour period with a brief rest between sessions. Comparison of the OSE-2000 and 3-D OCT-1000 CMT measurements was based on paired-t test. The mean difference between the CMT measurements was calculated. General linear model analyzed the relationships among eye (OD/OS), operator, sex, and CMT values using age as co-variant. All tests were considered statistically significant at P<0.05. The main outcome measures included CMT. RESULTS: When evaluated with general linear model analysis, CMT measurements were found to have high reproducibility across the two instruments between the two operators for the OSE-2000 single line scan and 3-D OCT-1000 macular scans (P=0.731; P=0.443). There was statistically significant difference in CMT values between the two instruments (P<0.001) and the mean difference was -46.83um at 95% confidence limits (-49.15,-44.51). Age was positively correlated with CMT (beta coefficient = 0.516, P=0.001; beta coefficient = 0.453, P=0.009) and sex was correlated with CMT from the OSE-2000 (P=0.021) but not with the 3-D OCT-1000 (P=0.056). According to the actual thickness measurements, the CMT of the male was thicker than the female's but there was no statistical difference. There was interaction between sex and eye in OSE-2000 and not in 3-D OCT-1000 (P=0.02; P=0.374). No significant correlation was found between CMT and the influencing factor of eye in both of the instruments (P=0.884; P=0.492). CONCLUSION: Reproducibility of CMT measurement using the two SD-OCTs is excellent in normal eyes according to the operator factor analysis. OSE-2000 has a different posterior retinal boundary of CMT measurement, which results in the CMT value differences, compared with the 3-D OCT-1000. Age is positively correlated with CMT measurement while sex is correlated with CMT in the OSE-2000 but not in the 3-D OCT-1000 and eye (OD/OS) had no correlation with CMT values. Mydriatic drops may not be necessary for CMT measurement using high scan rate SD-OCT in normal eyes in dark room. PMID- 22773988 TI - AcrySof phakic angle-supported intraocular lens for the correction of high to extremely high myopia: one-year follow-up results. AB - AIM: To assess the safety, efficacy and predictability of the AcrySof phakic angle-supported intraocular lens (IOL) (Alcon Inc., U.S.A.) for correction of high-to-extremely high myopia in adults. METHODS: In this prospective study performed in Tianjin Medical University Eye Center & College of Optometry, Tianjin, China, 25 eyes of 13 patients were implanted with AcrySof phakic angle supported IOLs and followed for 1 year postoperatively. Preoperative manifest refractive sphere was (-12.08+/-2.44) diopters (D) and cylinder was (-1.35+/ 0.62)D. Visual acuity, predictability and stability of manifest refraction spherical equivalent (MRSE), adverse events, and endothelial cell density were analyzed during 1-year of follow-up. RESULTS: After 1 year of follow-up, no eyes lost>=1 line (best spectacle-corrected visual acuity)BSCVA; an uncorrected visual acuity (UCVA) of 20/20 or better was achieved in 60% of eyes; 100% had an UCVA of 20/40 or better; a BSCVA of 20/30 or better was achieved by 100% of eyes; 84% had a BSCVA of 20/20 or better. The overall mean percentage change in endothelial cell density 1 year after surgery was (-0.27+/-3.60)%. Two eyes (8%) had increased intraocular pressure (IOP) on the day of surgery. No pupil ovalization, pupillary block, or retinal detachment events were observed. CONCLUSION: After 1 year of follow-up, the implantation of AcrySof phakic angle-supported IOL is proved to be safe, effective and predictable with minimal complications in patients with high-to-extremely high myopia. Due to the limitation of visiting time, long-term of clinical investigation is necessary to verify the safety and efficacy of this IOL. PMID- 22773989 TI - Data analysis of low dose multislice helical CT scan in orbital trauma. AB - AIM: To explore the optimal low dose of MSCT in orbital trauma examination. METHODS: Sixty transverse images of the fracture layer were selected. Low-dose images acquired at 30, 70, 100, 140, 170, and 200 milliampere (mA) were simulated by adding noise to the image space using software. After assessing the images according to the conditions of image quality and fracture, we found the optimal tube current that met diagnostic requirements and then applied it to clinical use. The CT Dose Index volume (CTDIvol), dose length product (DLP) and effective dose (ED) were recorded. The image quality was classified as good, fairly good, ordinary, poor, or very poor according to image level, noise, anatomic structure and whether the diagnostic requirements were met or not. The rank-sum test was used to perform statistical analysis on the ranked data. The Chi-square test was used for the numerical data. RESULTS: Under the scan conditions of a conventional dose of 300 mA, 60 cases of orbital fracture, 38 cases of orbital emphysema, 25 cases of ocular damage, and 3 cases of intraorbital foreign body were demonstrated in the images of the 60 orbital trauma patients. Among the low dose simulated images, the image quality difference of the different doses was of statistical significance (chi(2)=15.678, P=0.016). When the dose was lowered to 70 mA, the above mentioned clinical signs were still clear and diagnostic, however the image quality assessment results indicated that 2 cases were good, 16 cases were fairly good, and 42 cases were ordinary, poor or very poor. When the simulated dose tube current was 100mA, the image quality assessment results were 18 cases good, 34 cases fairly good, and 8 cases ordinary, poor and very poor; compared with the conventional dose, there was no statistical significance (P>0.05). When using a 100 mA tube current to examine 40 cases of orbital trauma patients in the clinic, the acquired image quality was 10 cases good, 26 cases fairly good and 4 cases ordinary, without any cases of poor or very poor. The CTDIvol, DLP and ED were 20.72mGy, 124.97 mGy.cm and 0.26mSv, respectively, while the CTDIvol, DLP and ED were 62.53mGy, 375.18 mGy*GTtl and 0.86mSv, respectively, when using a conventional dose of 300 mA. Compared with the tube current of 100 mA for scanning, the ED declined 70%. CONCLUSION: When conducting an MSCT scan for orbital trauma, the acquired images using the 100 mA tube current can meet the clinical diagnostic requirements, and the radiation dose to the patients can be decreased. PMID- 22773990 TI - Analysis of the relationship between postoperative ophthalmic complications and dialysis time of pre-kidney transplantation. AB - AIM: To determine the influence of the dialysis time before kidney transplantation on postoperative ophthalmic complications. METHODS: One hundred and eighty three patients who were given the follow-up after kidney transplantation were selected, including 124 males and 59 females. The dialysis time before kidney transplantation was (2.9+/-2.1) years. Among them, there were 93 cases having cadaveric renal transplantation and 90 cases having living relative renal transplantation. The conditions of ophthalmic complications in all the patients after kidney transplantation were investigated and the incidence rate on ophthalmic complications having different dialysis time before kidney transplantation was given Chi-square test and Chi-square linear trend test. RESULTS: Among 183 patients with kidney transplantation, 95 patients (51.9%) had at least one ophthalmic complication and the rest 88 patients (48.1%) had no significant abnormality at the eye region. The most common ophthalmic complications were pinguecula/conjunctival degeneration (31 cases), the following was caligo lentis (24 cases). The main manifestations were grayish white granule and plaque turbidity occurred in posterior capsule at the posterior pole of crystaline lens. The angulus iridocornealis of 5 patients (5.3%) with cataract and glaucoma were all open-angle through the detection by gonioscope. Through visual field examination, there were 2 patients with paracentral scotoma, 2 patients with arcuate scotoma and one case with nasal step. CONCLUSION: The experiments verify that the incidence of glaucomawas relates to the dialysis time before kidney transplantation, and the incidence rate might be higher if the dialysis time is longer. PMID- 22773991 TI - Effect of silicone oil removal on central corneal thickness. AB - AIM: To evaluate the effect of silicone oil removal(SOR) on central corneal thickness(CCT) in aphakic and pseudophakic eyes prospectively. METHODS: Patients who underwent SOR surgery between June 2005 - August 2007 were included in this study. Silicon oil was actively removed behind the posterior capsule through the pars plana sclerotomy site (posterior approach) in pseudophakic eyes and through the pupil and the corneal tunnel incision (anterior approach) in aphakic eyes with the 18-gauge cannula. CCT was assessed with Orbscan II corneal topography system preoperatively and at one month and three months postoperatively. A total of 34 eyes of 34 patients (26 males, 8 females) comprised the study group. Mean age was (55.6+/-12.3) years (Range: 25-80 years). Twenty-six eyes (76.5%) were pseudophakic and 8 (23.5%) aphakic. Mean time between silicone oil injection and removal was (15.1+/-13.6) months (Range: 5-54 months). At baseline, CCT was 576.4+/-46.0um in pseudophakic eyes and 611.6+/-36.2um in aphakic eyes. RESULTS: At the first postoperative month CCT was (573.3+/-40.1)um and (630.9+/-72.9)um in pseudophakic and aphakic eyes respectively. At the third postoperative month, CCT was (582.7+/-49.5)um and (614.5+/-82.4)um in pseudophakic and aphakic eyes respectively. There was no statistically significant difference in CCT measurements one month and 3 months after SOR when compared to preoperative values in both aphakic and pseudophakic eyes (P>0.05). CONCLUSION: Active SOR either by anterior or posterior approach did not affect the CCT. PMID- 22773992 TI - Low-fluence photodynamic therapy combinations in the treatment of exudative age related macular degeneration. AB - AIM: To compare the efficacy of low-fluence photodynamic therapy (PDT) combinations in the treatment of age-related macular degeneration (AMD). METHODS: Forty-five previously untreated eyes of 45 patients with exudative AMD whose best corrected visual acuity (BCVA) was >=0.3 (Snellen) were enrolled. 15 patients in Group I underwent low-fluence PDT (25J/cm(2)-300mW/cm(2)-83sec) and intravitreal pegaptanib combination, 15 patients in Group II underwent PDT (50J/cm(2) 600mW/cm(2)-83sec) and intravitreal pegaptanib combination while, 15 patients in Group III underwent intravitreal pegaptanib monotherapy. Complete ophthalmologic examinations were performed in pre and post treatment visits, and the results were statistically analised. A clinical activity score (CAS) was calculated by using changes in lesion size, amount of hemorrhage, staining pattern in FA and OCT measurement of intra/subretinal fluid. <= 3 logMAR lines of decrease in BCVA and decrease in CAS were considered as successful treatment. RESULTS: The mean age of 19 female (42.2%) and 26 male (57.8%) patients was 72.82+/-8.02 years. Mean follow-up was 13.93+/-5.87 months. Lesion type was occult in 28 eyes (62.2%). Treatment success rates according to BCVA assessments were 86.7%, 80%, 60% and mean BCVA decrease were 0.3, 1.0, 2.2 logMAR lines in Group I, II and III, respectively (P>0.05). According to the changes in central macular thickness and CAS, no difference was found among the study groups (P=0.850 and P=0.811, respectively). Patients treated with combination regimens had lower intravitreal injection frequencies (P=0.015). CONCLUSION: Combination regimen with intravitreal pegaptanib and low-fluence PDT seems to be safe and effective in stabilizing the clinical activity and BCVA in exudative AMD. PMID- 22773993 TI - Outcome of trabeculectomy in hospital Melaka, Malaysia. AB - AIM: To study the success and outcome of trabeculectomy in Hospital Melaka. METHODS: Medical records of all patients who underwent trabeculectomy between January 1, 2007 and October 31, 2010 whom were followed up for at least 6 months postoperatively in Hospital Melaka were retrospectively reviewed. RESULTS: A total number of 117 eyes of 91 patients with the age range between 12 to 84 years underwent primary trabeculectomy (n=20, 17.1%), combine trabeculectomy with cataract surgery (n=90, 76.9%), repeat trabeculectomy (n=5, 4.3%), and combine repeat trabeculectomy with cataract surgery (n=2, 1.7%). The disease spectrum includes primary open-angle glaucoma (POAG) (54 patients, 59.3%), priamry angle closure glaucoma (PACG) (14 patients, 15.4%), secondary glaucomas (19 patients, 20.9%) and juvenile glaucomas (4 patients, 4.4%). Preoperative mean intraocular pressure (IOP) was (24.69+/-8.67)mmHg as compared to postoperative mean IOP of (15.81+/-6.66)mmHg, (15.07+/-4.72)mmHg and (15.68 +/-3.65)mmHg at 6-month, 12 month and 24-month respectively. Eighty-two point one percent of eyes (n=96) achieved complete success (CS), 12.8% (n=15) with qualified success (QS) and only 5.1% (n=6) failed at 6 month with two of them warrant other filtering surgery. At twelve months, trabeculectomy with CS was 71.6% (n=63), QS in 22.7% (n=20) and failure in 5.7% (n=5). Sixty-seven point five percent (n=27) attained CS, 20.0% (n=8) with QS while 12.5% (n=5) failed at 24 month postoperative. CONCLUSION: As the understanding of the lower the IOP, the better the patients retaining the visual function, trabeculectomy is significantly a choice of treatment in uncontrolled glaucoma. This study concluded that trabeculectomy performed in Hospital Melaka has produced significant success as compared to other studies. PMID- 22773994 TI - Hyaluronidase in sub-Tenon's anesthesia for phacoemulsification, a double-blind randomized clinical trial. AB - AIM: To investigate the effect of hyaluronidase use on the quality of sub-Tenon's anaesthesia for phacoemulsification. METHODS: This was a randomized, double-blind clinical trial which was conducted at Nikookari Eye Hospital for 5 months. Forty two eyes of candidates for phacoemulsification under sub-Tenon's anaesthesia were randomly allocated to two equal groups and received either 2 mL of lidocaine 2% solution with (LH), or without (L) addition of hyaluronidase (150IU/mL). Akinesia was assessed 15 minutes after sub-Tenon's injection. Patients and surgeon's satisfaction, as well as the postoperative pain (the visual analogue scale, VAS) were investigated after operation. The contingency tables (including the Chi square or Fisher's exact tests, when appropriate) and parametric analysis (the independent samples t test) were used for statistical analysis. RESULTS: Complete akinesia (33.3% vs 4.8%, P=0.04), as well as the patients (85.7% vs 57.1%, P=0.04) and surgeon's satisfaction (87.5% vs 52.4%, P=0.02) were significantly more frequent in LH than in L group. The mean VAS was significantly lower in the same group (1.90+/-1.45 vs 3.00+/-1.55, P=0.04). CONCLUSION: Addition of hyaluronidase to lidocaine solution for sub-Tenon's anesthesia significantly improves the ocular akinesia, enhances the intra-operative patients and surgeons' satisfaction, and attenuates the postoperative pain. PMID- 22773995 TI - Sensory-neural hearing loss in pseudoexfoliation syndrome. AB - AIM: To evaluate relationship between ocular pseudoexfoliation syndrome(PXF) and sensory-neural hearing loss (SNHL). METHODS: This prospective case-control study was designed on patients who referred to a general ophthalmic clinic at Imam Khomeini Medical Center, Urmia, Iran (March 2010 through November 2010). On routine ophthalmic examination, patients diagnosed with ocular PXF were referred to the ENT department and, selected cases (after evaluating inclusion and exclusion criteria) were referred to Audiometric Department. Pure tone hearing threshold level(HTL) was measured at 1, 2, 3 kHz for each ear and was compared with International Standard (ISO 7029) median age associated hearing loss at 1, 2, 3 kHz (AAHL). RESULTS: Overall 21 of 50 patients (42.0%) had a higher HTL than the ISO 7029 median AAHL at 1, 2 and 3kHz, which included 14 ears of 23 patients in the male group (30.4%) and 21 ears of 27 patients in the female group (38.8%). Approximately 12.0% of patients had glaucoma at the same time, however; no significant correlation was found in SNHL prevalence and severity between PXF patient and patients with simultaneous glaucoma. SNHL was more common in patients with ocular PXF compared to their age- sex matched controls (P <0.05). CONCLUSION: Most of patients with ocular PXF had SNHL compared to their age-sex matched controls, which could be due to PXF fibrils in the inner ear. These findings suggest PXF could be a systemic disease. PMID- 22773996 TI - Meta analysis on the relationship between gene polymorphisms of vascular endothelial growth factor and retinal prognosis risk of prematurity. AB - AIM: To explore the relationship between gene polymorphisms of vascular endothelial growth factor (VEGF) and retinopathy of prematurity (ROP). METHODS: Literature materials related to gene polymorphisms of VEGF and ROP in PubMed, EMBASE, Cochrane and CBM database were retrieved. These materials were screened according to inclusion and exclusion standards. Patients diagnosed with ROP in clinic were regarded as control group and ROP patients who were in treatment were regarded as observation group. The indexes in two groups were matched except birth weight (BW), gender and gestational weeks. Meta5.1 was used to analyze the relationship between gene polymorphisms of VEGF and ROP. RESULTS: Four random control tests (RCT) were included in this research, including 2611 patients. Meta analysis results showed that VEGF affected ROP, having statistical significance. The combined ratio was 0.44 (95%CI, 0.07, 0.80), 0.42 (95%CI, 0.09, 0.74) and 0.75 (95%CI, 0.02, 1.49), respectively. Carrying +405 allele might increase the premature infants' risk of having ROP. CONCLUSION: ROP may be related to its carrying of +405 allele. Large-scale, multi-factor RCT researches are still needed in order to identify the relation between VEGF and ROP. PMID- 22773997 TI - Optical coherence tomography assessed retinal nerve fiber layer thickness in patients with Alzheimer's disease: a meta-analysis. AB - AIM: To investigate the difference of retinal nerve fiber layer (RNFL) thickness between Alzheimer's disease patients and normal people, so as to provide clue for the early diagnosis of Alzheimer's disease. METHODS: The articles on the association of RNFL thickness and Alzheimer's disease were retrieved by searching international and national databases. The qualified articles were assessed by meta analysis with Stata11.0 software. The results were pooled using weighted mean difference (WMD) with a corresponding 95% confidence interval (CI). RESULTS: Totally 7 studies enrolled 324 eyes were included in the meta-analysis. The results of meta analysis showed that in AD patients, there was a significant average RNFL thickness reduction compared with the control group [WMD=-17.561, 95%CI: (-23.971, -11.151)]. There were significant differences in superior, inferior, nasal and temporal RNFL thickness between the two groups. WMD with a 95%CI were [-18.829, 95%CI:(-25.915, -11.743); P<0.05], [-25.775, 95%CI:(-34.304, -17.247); P<0.05], [-16.877, 95%CI: (-29.141, -4.613); P<0.001] and [-14.565, 95%CI:(-28.002, -1.128); P<0.001] respectively. Begg's test and Egger's test did not show significant difference, funnel plot was basically symmetrical, indicating that there was no publication bias existed. CONCLUSION: There are significant differences in the RNFL thickness in all quadrants between the two groups. RNFL thickness is reduced in AD patients compared with the control group. PMID- 22773998 TI - Bilateral capsule contraction syndrome following pathological myopic cataract surgeries. PMID- 22773999 TI - Simple and covalent fabrication of a paper device and its application in sensitive chemiluminescence immunoassay. AB - In this paper, chemiluminescence immunoassay (CLIA) was introduced into the recently proposed microfluidic paper-based analytical devices (MUPADs) through covalent fabrication strategy for the first time. This novel paper-based CLIA, with high-throughput, rapid, stable and reusable CL response to trace amounts of analyte in real biological samples, combines the simplicity and low-cost of the MUPADs with the high sensitivity and selectivity of CLIA. Periodate oxidation, which can form covalent bonds between polysaccharides and proteins, was used for activation of MUPADs to covalently immobilize antibodies on MUPADs in this work for the first time. Thus, the paper-based sandwich CLIA and regeneration of it can be easily realized for further development of this technique in sensitive, specific and low-cost applications. The application test of this paper-based CLIA was successfully performed, as a model, through the determination of biomarkers in human serum on paper microzone plate. The paper-based CLIA will be very useful when the level of an analyte in real biological sample is important for point-of care testing, public health and environmental monitoring in remote regions, developing or developed countries. PMID- 22774001 TI - Fabrication of glutathione photoelectrochemical biosensor using graphene-CdS nanocomposites. AB - A novel glutathione (GSH) photoelectrochemical biosensor was fabricated using the newly synthesized graphene-CdS (GR-CdS) nanocomposites. The GR-CdS nanocomposites were prepared by a fast, one-step, aqueous reaction. The as-prepared GR-CdS structure inherited the excellent electron transport of GR and facilitated the spatial separation of photo-generated charge carrier, therefore resulting in the enhanced photocurrent, and making it a promising candidate for developing photoelectrochemical biosensors. The proposed GSH sensor displays satisfactory analytical performance with an acceptable linear range from 0.01 to 1.5 mmol L( 1) with a detection limit of 0.003 mmol L(-1) at a signal-to-noise ratio of 3, and also shows an excellent specificity against anticancer drugs and can be successfully applied for GSH detection in real samples. The as-synthesized GR-CdS nanocomposites exhibited obviously enhanced photovoltaic properties, which could be extended to the detection of other enzymes and biomolecules, thus providing a promising platform for the development of photoelectrochemical biosensors. PMID- 22774000 TI - Electrochemical analysis based on nanoporous structures. AB - Analytical applications and the underlying principles of unique electrochemistry in nanoporous structures are reviewed and discussed. In addition to the conventional concept of enlarged surface area, the structural effects of nanoporous materials can play significant roles such as discriminative electrokinetics, the nano-confinement effect, electrical double layer overlapping, ion-selective impedance, etc. The applications described in this review article include solid-state pH sensors, miniaturized pseudo-reference electrodes, nonenzymatic glucose monitoring, ion diodes, transistors, extracellular neural probes, and a few more. Further intensive research is required to develop creative analytical tools based on nanoporous structures and to unravel the underlying physicochemical principles. PMID- 22774003 TI - Bonding between strongly repulsive metal atoms: an oxymoron made real in a confined space of endohedral metallofullerenes. AB - Endohedral metallofullerenes (EMFs) are able to encapsulate up to four metal atoms. In EMFs, metal atoms are positively charged because of the electron transfer from the endohedral metal atoms to the carbon cage. It results in the strong Coulomb repulsion between the positively charged ions trapped in the confined inner space of the fullerene. At the same time, in many EMFs, such as Lu(2)@C(76), Y(2)@C(79)N, M(2)@C(82) (M = Sc, Y, Lu, etc.), Y(3)@C(80), or Sc(4)O(2)@C(80), metals do not adopt their highest oxidation states, thus yielding a possibility of the covalent metal-metal bonding. In some other EMFs (e.g., La(2)@C(80)), metal-metal bonding evolves as the result of the electrochemical or chemical reduction, which leads to the population of the metal based LUMO with pronounced metal-metal bonding character. This article highlights different aspects of the metal-metal bonding in EMFs. It is concluded that the valence state of the metal atoms in dimetallofullerenes is not dependent on their third ionization potential, but is determined by their ns(2)(n- 1)d(1)->ns(1)(n- 1)d(2) excitation energies. Peculiarities of the metal-metal bonding in EMFs are described in terms of molecular orbital analysis as well as topological approaches such as Quantum Theory of Atoms in Molecules and Electron Localization Function. Interplay of Coulomb repulsion and covalent bonding is analyzed in the framework of the Interacting Quantum Atom approach. PMID- 22774002 TI - Tuning delamination of layered covalent organic frameworks through structural design. AB - Exfoliation of a family of polyacetylenic porous layered covalent organic frameworks by means of a simple sonication procedure results in the obtention of nanolayer structures as observed by AFM and TEM measurements. Systematic AFM analysis of the isolated nanostructures reveals that the degree of exfoliation depends on the polymer architecture, thinner layers being observed when the pore size decreases. PMID- 22774004 TI - A proteogenomic survey of the Medicago truncatula genome. AB - Peptide sequencing by computational assignment of tandem mass spectra to a database of putative protein sequences provides an independent approach to confirming or refuting protein predictions based on large-scale DNA and RNA sequencing efforts. This use of mass spectrometrically-derived sequence data for testing and refining predicted gene models has been termed proteogenomics. We report herein the application of proteogenomic methodology to a database of 10.9 million tandem mass spectra collected over a period of two years from proteolytically generated peptides isolated from the model legume Medicago truncatula. These spectra were searched against a database of predicted M. truncatula protein sequences generated from public databases, in silico gene model predictions, and a whole-genome six-frame translation. This search identified 78,647 distinct peptide sequences, and a comparison with the publicly available proteome from the recently published M. truncatula genome supported translation of 9,843 existing gene models and identified 1,568 novel peptides suggesting corrections or additions to the current annotations. Each supporting and novel peptide was independently validated using mRNA-derived deep sequencing coverage and an overall correlation of 93% between the two data types was observed. We have additionally highlighted examples of several aspects of structural annotation for which tandem MS provides unique evidence not easily obtainable through typical DNA or RNA sequencing. Proteogenomic analysis is a valuable and unique source of information for the structural annotation of genomes and should be included in such efforts to ensure that the genome models used by biologists mirror as accurately as possible what is present in the cell. PMID- 22774005 TI - Technics of touch in the neonatal intensive care. AB - Medical technologies, although often crucial for the provision of healthcare, may carry unintended significance for patients and their families. The highly technicised neonatal intensive care unit (NICU) is the place where parents of hospitalised baby have their early encounters with their child. The aim of this study is to investigate phenomenologically how the contact and relation between parent and child may be affected by the mediating presence and use of the techno medical features and equipments of the NICU. Three common technologies are examined for the ways they condition the kinds of contact afforded between parents and child: the isolette, the feeding tube and the brain imaging equipment. The concluding recommendations speak of the need for understanding the relational experiences of parents of hospitalised babies, and the tactful sensitivities required of the healthcare teams who provide care to these families. PMID- 22774205 TI - The critical role of amino acid residue at position 117 of mouse UDP glucuronosyltransfererase 1a6a and 1a6b in resveratrol glucuronidation. AB - Mouse UDP-glucuronosyltransferase 1a6 (Ugt1a6) contains two functional copies of 1a6a and 1a6b that share high sequence homology (98%). Only 10 amino acids located around the substrate recognition region are different out of 531 total residues. Although Ugt1a6 plays important roles in conjugating phenolic compounds, the functional characteristics of these isozymes are unclear. We performed functional analyses of mouse Ugt1a6a and Ugt1a6b using two isomeric polyphenols (trans- and cis-resveratrol). The cDNAs of mouse Ugt1a6a and Ugt1a6b were cloned and constructed as recombinant proteins using a yeast expression system, and kinetic parameters were evaluated. The wild-type Ugt1a6a and Ugt1a6b proteins catalysed trans- and cis-resveratrol 3-O-glucuronidation. Although the K(m) value for trans-resveratrol was significantly lower for Ugt1a6a compared with Ugt1a6b, the K(m) values for cis-resveratrol were comparable for the isozymes. Despite high sequence homology, significant kinetic differences were observed between the isozymes. To identify the critical residues for resveratrol glucuronidation, we constructed 10 variants of Ugt1a6a (T81P, N96R, H98Q, L100V, S104P, N115S, I117L, V118T, V119L and D120E). The I117L variant had Ugt1a6b-like enzymatic properties of K(m) in trans-resveratrol, and V(max) and K(si) in cis form, suggesting that the residues located at position 117 of Ugt1a6a and Ugt1a6b play an important role in resveratrol glucuronidation. PMID- 22774206 TI - A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer. AB - CONTEXT/OBJECTIVES: Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC). DESIGN/SETTING/PATIENTS/INTERVENTIONS/OUTCOME MEASURES: Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90% chance of detecting a response rate of >20% at the 0.10 significance level when the true response rate is >5%), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response. RESULTS: Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7% were female, median age was 66 yr (range 45-77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13%) and pharyngolaryngeal pain (13%). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatment-related tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease. CONCLUSIONS: Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC. PMID- 22774207 TI - GLP-1 and glucagon secretion from a pancreatic neuroendocrine tumor causing diabetes and hyperinsulinemic hypoglycemia. AB - CONTEXT: Glucagon-like peptide-1 (GLP-1) is a gut peptide that promotes insulin release from pancreatic beta-cells and stimulates beta-cell hyperplasia. GLP-1 secretion causing hypoglycemia has been described once from an ovarian neuroendocrine tumor (NET) but has not been reported from a pancreatic NET (pNET). OBJECTIVE: A 56-yr-old male with a previous diagnosis of diabetes presented with fasting hypoglycemia and was found to have a metastatic pNET secreting glucagon. Neither the primary tumor nor metastases stained for insulin, whereas the resected normal pancreas showed histological evidence of islet cell hyperplasia. We provide evidence that GLP-1 secretion from the tumor was the cause of hyperinsulinemic hypoglycemia. METHODS: GLP-1 levels were determined in the patient, and immunohistochemistry for GLP-1 was performed on the tumor metastases. Ex vivo tissue culture and a bioassay constructed by transplantation of tumor into nude mice were performed to examine the tumor secretory products and their effects on islet cell function. RESULTS: The patient had high levels of glucagon and GLP-1 with an exaggerated GLP-1 response to oral glucose. Immunohistochemistry and primary tissue culture demonstrated secretion of glucagon and GLP-1 from the tumor metastases, whereas insulin secretion was almost undetectable. Ex vivo coculture of the tumor with normal human islets resulted in inhibition of insulin release, and transplanted mice developed impaired glucose tolerance. CONCLUSIONS: This is the first description of glucagon and GLP-1 secretion from a metastatic pNET causing sequential diabetes and hypoglycemia. Hypoglycemia was caused by insulin secretion from hyperplastic beta-cells stimulated by tumor-derived GLP-1. PMID- 22774208 TI - Approach to the patient with persistent hyperprolactinemia and negative sellar imaging. AB - Hyperprolactinemia is a common cause of menstrual disturbances affecting young women. There is a diversity of causes, from physiological, such as pregnancy, to pharmacological and pathological, such as hypothyroidism. Renal and hepatic failure, intercostal nerve stimulation by trauma or surgery, prolactinomas, other tumors in the hypothalamus-pituitary region, as well as macroprolactinemia can also be considered. Identifying the correct cause is important to establish the correct treatment. Should all these causes be ruled out and pituitary imaging revealed as negative, idiopathic hyperprolactinemia is therefore diagnosed. In symptomatic patients, treatment with dopaminergic agonists is indicated. As for the asymptomatic hyperprolactinemic individuals, macroprolactinemia should be screened, and once it is detected, there is no need for pituitary imaging study or for dopaminergic agonist use. PMID- 22774209 TI - What is "metabolically healthy obesity"?: from epidemiology to pathophysiological insights. PMID- 22774211 TI - Antithyroid drug treatment in pregnancy. PMID- 22774210 TI - Persistence pays off for PCOS gene prospectors. PMID- 22774212 TI - Disorders of sex development: challenges for the future. PMID- 22774219 TI - Death certification: do consultant pathologists do it better? AB - The completion of the medical certificate of cause of death is required for registration of a death, and this data helps plan healthcare services for the country. Many audits have shown them to be inaccurately completed by junior doctors, but the authors examined whether advice from consultant pathologists could improve this. Using the Office for National Statistics guidelines, the authors found that only 56% of the certificates were appropriately completed. The planned introduction of medical examiners to England and Wales is aimed at improving this situation, but consultant pathologists will still issue causes of death following postmortems, and it would seem prudent to train pathologists as well. PMID- 22774213 TI - BRAFV600E mutation and papillary thyroid cancer: chicken or egg? PMID- 22774220 TI - Familial haemophagocytic lymphohistiocytosis-related plasma cell neoplasm: a case report. PMID- 22774221 TI - Professor Bryan F Warren: an appreciation (15 April 1958-28 March 2012). PMID- 22774224 TI - Retraction: Shang E, Hasenberg T. Aerobic endurance training improves weight loss, body composition, and co-morbidities in patients after laparoscopic Roux-en Y gastric bypass. Surg Obes Relat Dis 2010;6:260-6. PMID- 22774222 TI - Retrospective review of diagnostic histopathology samples in research projects: transparency should be the practice with respect to diagnostic discordance. AB - Retrospective review of diagnostic histopathology samples in secondary research projects may generate cases with discordance in diagnosis between the pathologist originally signing out the sample and the reviewer. In this article the authors discuss ethical and legal issues involved in secondary review and propose how diagnostic discrepancies in research projects can be handled. Research participants have the right to know about and control the handling of personal data. Researchers have a duty to inform research participants about research findings of relevance to the current or future health or quality of life. Such feedback is to be provided within a healthcare framework. The authors recommend that pathology laboratories should require researchers to provide feedback on diagnostic discrepancies of potentially clinical significance in secondary research projects using retrospective review of diagnostic histopathology material. The pathology laboratory in charge of the archival material should be responsible for the follow-up on such cases. PMID- 22774225 TI - Analytic solutions and universal properties of sugar loading models in Munch phloem flow. AB - The transport of sugars in the phloem vascular system of plants is believed to be driven by osmotic pressure differences according to the Munch hypothesis. Thus, the translocation process is viewed as a passive reaction to the active sugar loading in the leaves and sugar unloading in roots and other places of growth or storage. The modelling of the loading and unloading mechanism is thus a key ingredient in the mathematical description of such flows, but the influence of particular choices of loading functions on the translocation characteristics is not well understood. Most of the work has relied on numerical solutions, which makes it difficult to draw general conclusions. Here, we present analytic solutions to the Munch-Horwitz flow equations when the loading and unloading rates are assumed to be linear functions of the concentration, thus allowing them to depend on the local osmotic pressure. We are able to solve the equations analytically for very small and very large Munch numbers (e.g., very small and very large viscosity) for the flow velocity and sugar concentration as a function of the geometric and material parameters of the system. We further show, somewhat surprisingly, that the constant loading case can be solved along the same lines and we speculate on possible universal properties of different loading and unloading functions applied in the literature. PMID- 22774226 TI - A general ploidy model for the evolution of helping in viscous populations. AB - There is growing interest in understanding how kin selection drives the evolution of social behaviours in viscous populations. A key result, that has inspired much work on this topic, is the exact cancellation of the genetic relatedness and kin competition effects of dispersal in the simplest models of population viscosity, such that a reduction in the rate of dispersal neither promotes nor inhibits the evolution of helping behaviour. This theoretical result has been demonstrated for populations characterised by haploid, diploid and haplodiploid modes of inheritance. Here we develop a model of general ploidy that recovers these three scenarios as special cases and allows examination of scenarios that have not been considered previously. Specifically, we: clarify the importance of the implicit assumption of monandry in previous models; show that the cancellation result obtains in some models of ploidy but not in others; and reveal that the cancellation result obtains for different reasons in different models of ploidy. The cancellation result therefore hinges upon a population's genetic system as well as its demography. PMID- 22774227 TI - Neuropharmacological specificity of brain structures involved in soman-induced seizures. AB - Pharmacological control of seizure activity following nerve agent exposure is critical in reducing neuropathology and improving survival in casualties. Three classes of drugs, anticholinergics, benzodiazepines and excitatory amino acid (EAA) antagonists, have been shown to be effective at moderating nerve agent induced seizures. However, little is known about which brain structures are involved in producing the anticonvulsant response. This study evaluated drugs from each class, injected directly into one of three specific brain structures, the perirhinal cortex, the entorhinal cortex, or the mediodorsal thalamus, for their ability to modulate seizures induced by the nerve agent soman. The drugs evaluated were the anticholinergic scopolamine, the benzodiazepine midazolam, and the EAA antagonist MK-801. For each drug treatment in each brain area, anticonvulsant ED50 values were calculated using an up-down dosing procedure over successive animals. There was no statistical difference in the anticonvulsant ED50 values for scopolamine and MK-801 in the perirhinal and entorhinal cortices. MK-801 pretreatment in the mediodorsal thalamus had a significantly lower anticonvulsant ED50 value than any other treatment/injection site combination. Midazolam required significantly higher doses than scopolamine and MK-801 in the perirhinal and entorhinal cortices to produce an anticonvulsant response and was ineffective in the mediodorsal thalamus. These findings support the contention that specific neuroanatomical pathways are activated during nerve agentinduced seizures and that the discrete brain structures involved have unique pharmacological thresholds for producing an anticonvulsant response. This study is also the first to show the involvement of the mediodorsal thalamus in the control of nerve agent-induced seizures. PMID- 22774228 TI - Parkinson's disease and the environment: beyond pesticides. PMID- 22774229 TI - Efficacy of biomarkers and personalized cancer therapeutics. Abstracts of the 4th WIN Symposium. June 28-29, 2012. Paris, France. PMID- 22774231 TI - Abstracts of the ESMO (European Society for Medical Oncology) 14th World Congress on Gastrointestinal Cancer. June 27-30, 2012. Barcelona, Spain. PMID- 22774230 TI - Abstracts of the 57th Annual Meeting of the Plastic Surgery Research Council. June 14-16, 2012. Ann Arbor, Michigan, USA. PMID- 22774232 TI - Cancer stem cells and metastasis. AB - Cancer stem cells (CSCs) represent a subpopulation of tumour cells endowed with self-renewal and multi-lineage differentiation capacity but also with an innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in cancer patients. Operationally, CSCs are defined by their tumour-propagating ability when serially transplanted into immune-compromised mice and by their capacity to fully recapitulate the original heterogeneity of cell types observed in the primary lesions they are derived from. CSCs were first identified in haematopoietic malignancies and later in a broad spectrum of solid tumours including those of the breast, colon and brain. Notably, several CSC characteristics are relevant to metastasis, such as motility, invasiveness and, as mentioned above, resistance to DNA damage-induced apoptosis. Here, we have reviewed the current literature on the relation between CSCs and metastasis formation. Preliminary studies on cancer cell lines and patient-derived material suggest a rate-limiting role for stem-like cells in the processes of tumour cell dissemination and metastasis formation. However, additional studies are needed to deliver formal proof of their identity as the cell of origin of recurrences at distant organ sites. Nevertheless, several studies have already provided pre clinical evidence of the efficacy of novel therapies directed against disseminated CSCs. PMID- 22774233 TI - Partial benefit of anastrozole in the long-term treatment of precocious puberty in McCune-Albright syndrome. AB - We report a long-term follow-up on the use of anastrozole in the treatment of peripheral precocious puberty (PP) in McCune-Albright syndrome (MAS). A girl, age 3 years and 9 months, was diagnosed with MAS due to PP, cafe-au-lait spots, and polyostotic fibrous dysplasia. Serum estradiol was elevated, and gonadotropins were suppressed. Pelvic ultrasound showed an enlarged uterus and a follicle cyst (13 mm) in the left ovary. Bone scintigraphy showed osteogenic lesions on the skull, humerus, tibia, and acetabulum. Bone age was 3 years and 5 months at the chronological age of 3 years. After 36 months of treatment with anastrozole (1 mg/day), there was suppression of breast growth, normalization of growth velocity and serum estradiol, and disappearance of ovarian cysts. However, there was increase in uterine volume, advancement of bone age, and two episodes of vaginal bleeding (18th and 24th months). This report shows the partial benefit of anastrozole in the treatment of peripheral PP of girls with MAS. PMID- 22774234 TI - Worker injuries and safety equipment in Ohio nursing homes. AB - A survey of Ohio nursing homes was conducted in 2007 to examine whether injury rates were related to facility characteristics and availability of safety equipment. The median rate of injury in the 898 facilities was 5.7 injuries per 100 workers per year. Although 95% of the facilities had written resident lift ing policies, only 22% of these were zero-lift policies. Gait transfer belts(99%) and portable total-lift hoists(96%) were common, whereas ceiling-mounted total lift hoists were rarely reported (7%). In a multivariable analysis, injury rate ratios increased with the proportion of residents using wheel-chairs and were lower in smaller facilities. Facilities without a lifting policy had a higher estimated injury rate than facilities without such a policy; however, none of the safety equipment was associated with significant changes in injury rates. More information, such as frequency of use and access to ver-sus availability of equipment, may be needed to better understand the im-pact of safety equipment on nursing home worker injury rates. PMID- 22774235 TI - [Increase in incidence of drug treatments, ethical principles and conflict of interest in cooperation with the pharmaceutical industry]. PMID- 22774236 TI - Atrial fibrillation. Prevent stroke, stop symptoms. PMID- 22774237 TI - Health tips. Changes in stool cooler. PMID- 22774238 TI - A high-fiber diet may help you live longer. PMID- 22774239 TI - More on red wine and breast cancer risk. PMID- 22774240 TI - Palliative care. More than hospice. PMID- 22774241 TI - Stopping smoking. Risks and rewards. PMID- 22774243 TI - I read that one good thing about being overweight or obese is that you don't have to worry about having a bone fracture from osteoporosis. Is this true? PMID- 22774242 TI - Coffee and health. The latest buzz. PMID- 22774244 TI - What is a PET scan? PMID- 22774245 TI - Major fat-burning discovery. Harvard researchers discover a hormone released by exercise. PMID- 22774246 TI - Ask the doctor. My lower leg hurts when I walk. Could it be peripheral artery disease? PMID- 22774247 TI - Ask the doctor. Brown age spot on my face seems to be getting larger. Should I be concerned? PMID- 22774248 TI - Overeating may reduce brain function. High caloric intake could raise the risk of memory loss. PMID- 22774249 TI - Grieving may trigger heart attack. PMID- 22774250 TI - New knee helps your heart. Today's high-tech procedure offers more benefits. PMID- 22774252 TI - Sex after heart attack. The American Heart Association says it's safe. PMID- 22774251 TI - Dieting? Have some cake. Could your favorite treat help you lose weight? PMID- 22774253 TI - Triglycerides may predict stroke. This lipid plays a bigger part than you realize. PMID- 22774254 TI - Eve surgery and post-op pain. Contact lenses with vitamin E deliver long-lasting anesthetic. PMID- 22774255 TI - Better way to apply sun screen. A Harvard expert says most people don't use enough. PMID- 22774256 TI - Beta blockers. What you need to know about these blood pressure drugs. PMID- 22774257 TI - Flavonoids may help protect against Parkinson's disease. PMID- 22774258 TI - Metal-on-metal hip replacements don't increase cancer risk. PMID- 22774259 TI - Low blood pressure when standing could signal heart failure. PMID- 22774261 TI - New study highlights value of colon cancer screenings. PMID- 22774260 TI - Combination therapy no advantage in Alzheimer's treatment. PMID- 22774262 TI - FDA calls for voluntary label changes,increased veterinarian oversight. PMID- 22774263 TI - Improving the safety of pet food: new efforts emphasize preventive measures in manufacturing. PMID- 22774264 TI - BSE found in dairy cow. PMID- 22774265 TI - Experience with Western University CVM graduates. PMID- 22774266 TI - Support for AVMA position on animal welfare standards. PMID- 22774267 TI - Pet owner's pledge. PMID- 22774268 TI - Spotted hemlock poisoning in a herd of Angus cattle. PMID- 22774269 TI - Qualitative benefits of screening for intimate partner violence. PMID- 22774271 TI - Room for improvement. PMID- 22774272 TI - Texts put more pressure on overstretched school nurses. PMID- 22774274 TI - Inspired to take up nursing abroad. PMID- 22774273 TI - Lessons learned from bacteria outbreak. PMID- 22774275 TI - Multiprofessional education: improving care for acutely ill children. AB - A three-year programme was established for practitioners who work with acutely ill and injured children and young people. Courses were held in urban and rural areas of Scotland and more than 2,000 NHS staff, including nurses, paramedics, doctors and allied health professionals, took part. Three-day training comprised clinical skills updates, scenario-based teaching and observed structural clinical examinations. As a result, NHS Scotland says care delivery to children, young people and their families has improved in community and hospital environments. PMID- 22774276 TI - Caring for a child with Down's syndrome in the acute care setting. AB - This article discusses Down's syndrome and its effect on the child. Some common medical conditions that may necessitate a child with Down's syndrome attending hospital either as an inpatient or an outpatient are identified. These include cardiac disease, atlantoaxial instability, growth, thyroid function and eye, ear, nose and throat issues. The nurse's role in minimising the stress involved for the child and the family is discussed. Practical suggestions are offered for ways of enhancing practice and improving outcomes, specifically in the area of communicating with the child and family. PMID- 22774277 TI - Exploring the experiences and expectations of year 1 children's nursing students. AB - BACKGROUND: Attrition among children's nursing students remains high despite the field of practice attracting large numbers of applicants. While previous studies have examined nursing students as a group, this study specifically examines the children's nursing student experience. AIM: To explore the expectations and early experiences of children's nursing students. METHOD: A phenomenological approach was adopted. Four focus groups were conducted at the beginning and end of the first year of a three-year programme. FINDINGS: The students defined children's nursing by the age and needs of the client group. They had expected practice experience would solely be within the acute setting. The acquisition and confidence in undertaking psychomotor skills was of importance to this group of students. CONCLUSION: The students' unmet expectations may have a negative effect on their experience of the programme and therefore potentially on their decision to continue on the programme. PMID- 22774278 TI - Maintaining good practice in the administration of medicines to children. AB - This article discusses the role of the children's nurse in the administration of medicines to children. What is meant by the phrase 'off label' is explained, along with the legal processes involved in ensuring medicines are safe to be administered to children, and the ethical issues behind the practice of crushing and disguising medication. Areas where errors can occur are identified and the importance of assessing each child and minimising harm are emphasised. PMID- 22774279 TI - Who's in the driver's seat? PMID- 22774280 TI - Celebrating innovation in palliative care. PMID- 22774281 TI - Strategically managing health care costs. PMID- 22774282 TI - Sounding the alarm. Alarm fatigue to get heightened attention. PMID- 22774283 TI - Healthy staff. Walking off the pounds... right to the bank. PMID- 22774284 TI - Right care, right place. Hospitals expand progressive care. PMID- 22774285 TI - Back to school. Leadership academy gives doctors skills for a new era. PMID- 22774286 TI - Keeping tabs on IT projects. PMID- 22774287 TI - The mental health crisis. AB - Public funding for behavioral health care continues to dwindle, and the number of psych facilities and providers can't meet the demand. What are some hospitals doing to avert a growing crisis? PMID- 22774288 TI - Transforming care delivery. Interview by Bob Kehoe. PMID- 22774289 TI - CNO. Focus on the C-suite: frontliner-in-chief. PMID- 22774290 TI - Hospital engagement networks: 10 big goals in 2 short years. AB - The national HEN project and its 3,900 hospitals take the quality and safety movement to a whole new level, proponents say. Everyone hopes the $200 million investment pays off handsomely in a short time. PMID- 22774291 TI - Antimicrobial stewardship: it's time to step it up. AB - Hospitals that use antibiotics wisely can reduce lengths of stay and morbidity and mortality, and save on costs. Here are keys to an antimicrobial stewardship program. PMID- 22774292 TI - Reinvention. Health care organizations start overhauls for a new delivery model. PMID- 22774293 TI - Managing the transition. The role of governance. PMID- 22774294 TI - The hospital of the future. Strategies for success. PMID- 22774295 TI - The capital challenge. Think outside the box. PMID- 22774296 TI - Committing to change. Enabling accountable care. PMID- 22774297 TI - Physician engagement. Partnering for collaboration. PMID- 22774298 TI - Clinical integration. The foundation of our future. PMID- 22774299 TI - Where need--and appreciation--overwhelm. A New Jersey hospitalist brings a kind of Christmas in July to his native Nigerian village. PMID- 22774300 TI - Seeing device costs clearly. PMID- 22774301 TI - Prevalence of metabolic syndrome among hypertensive patients in Abuja, Nigeria. AB - BACKGROUND: It is well known that factors like high blood pressure, hyperglycemia, dyslipidemia, obesity and hyperuricemia tend to cluster together giving rise to what is called metabolic syndrome. In spite of the high prevalence of hypertension in Nigeria, there is a dearth of data describing the prevalence of metabolic syndrome in Nigerian hypertensive patients. We therefore set out to look at the prevalence of metabolic syndrome in hypertensive patients presenting to the cardiology clinic of a tertiary institution in Abuja, Nigeria. METHODS: Metabolic syndrome was defined in patients according to the World Health Organisation's definition. RESULTS: Of the 362 patients studied, 56.9% were male and 43.1% were female. The mean age was 51.80 +/- 11.63 years, mean duration of hypertension was 8.90 +/- 3.95 years, mean body mass index was 29.36 +/- 6.12 kg/m2 and mean arterial blood pressure was 110.28 +/- 18.17 mm Hg. Overall, 13.0% of the study population had metabolic syndrome; 16.7% of females and 10.2% of males. CONCLUSION: The prevalence of metabolic syndrome among hypertensive patients in Abuja, Nigeria is comparable to rates observed in some general populations in Europe. This might imply the epidemiological transition in disease pattern already being experienced in many parts of sub-Saharan Africa. PMID- 22774302 TI - Cardiovascular and diabetes risk perception in a Hispanic community sample. AB - PURPOSE: We examined perceptions of 10-year coronary heart disease (CHD) risk or likelihood of having undiagnosed diabetes or impaired fasting glucose (IFG) with actual risk in a community sample of Hispanic adults. METHODS: We conducted a survey of 183 Hispanic adults (> or =18 years) recruited at community events around Charleston, SC. Likelihood of having undiagnosed diabetes/IFG as well as 10-year CHD risk were calculated. Perceived risk was assessed with questions based on the Risk Perception Survey-Diabetes Mellitus. RESULTS: Over half of respondents (54.8%) underestimated their likelihood of undiagnosed diabetes/IFG and 14.8% underestimated their 10-year CHD risk. Older and overweight respondents were more likely to underestimate their likelihood of undiagnosed diabetes/IFG. Respondents with family history of diabetes were the least likely to underestimate their likelihood of current undiagnosed diabetes/IFG. Respondents with diagnosed hypertension, diabetes, high cholesterol or a family history of heart attack were more likely to underestimate their 10-year CHD risk. Men were more likely to underestimate their risk for diabetes/IFG and CHD risk. CONCLUSIONS: Health education to improve accurate risk perception could improve health promotion for this population. PMID- 22774303 TI - Coronary angiographic findings and conventional coronary artery disease risk factors of Indo-Guyanese immigrants with stable angina pectoris and acute coronary syndromes. AB - BACKGROUND: The prevalence of coronary artery disease (CAD) among migrant Indian populations exceeds that of Caucasians. Migrant Indians also suffer from more premature, clinically aggressive and angiographically extensive, (i.e., 3-vessel disease). It is not known whether the extent of angiographic CAD or the conventional CAD risk factors of Indo-Guyanese (IG) immigrants differs from that of Caucasians. METHODS: We reviewed the conventional CAD risk factors and angiographic findings of 198 IG and 191 Caucasians who were consecutively referred for cardiac catheterization with a diagnosis of stable angina pectoris or acute coronary syndrome. RESULTS: Three-vessel CAD was approximately 1.5 times more common among IG than Caucasians (34.8% vs. 24.0%; P = .02). Age (P = .01), male sex (P = .03) and diabetes mellitus (P = .05) were independently associated with an increased likelihood of 3-vessel CAD and there was a trend towards IG ethnicity predicting 3-vessel disease (P = .13). The frequency of diabetes mellitus (51.5% vs. 30.9%; P <.001), hypertension (82.3% vs. 67.0%; P < .001) and dyslipidemia (75.5% vs. 60.2%; P = .001) were significantly greater among IG, however, that of smoking was not. While IG were significantly leaner than Caucasians (27.7 kg/m2 vs. 30.0 kg/m2 ; P < .001), their mean body mass index fell within the ethnic-specific range for obesity. CONCLUSIONS: We conclude that IG immigrants presenting for coronary angiography have significantly higher rates of 3-vessel CAD as well as higher rates of diabetes mellitus, hypertension and dyslipidemia than Caucasians. Aggressive screening, prevention and treatment may be warranted in this cohort. PMID- 22774304 TI - Racial/ethnic disparities, social support, and depression: examining a social determinant of mental health. AB - OBJECTIVE: We examined the risk of depression as it relates to social support among individuals from African American, Caribbean black, and non-Hispanic White backgrounds. METHODS: 6,082 individuals participated in the national survey of American life (NSAL), a nationally representative, psychiatric epidemiological, cross-sectional survey of household populations. The survey is designed to explore racial and ethnic differences in mental disorders. NSAL survey questions were used as a proxy for social support. Logistic regression analysis was used to examine the correlates between having a DSM-IV diagnosis of major depressive disorder in the past year, demographic variables, and social support. RESULTS: African American race/ethnicity was associated with decreased odds of depression when compared to non-Hispanic whites, even when controlling for social support variables and demographics (OR = 0.51, 95% CI = 0.43-0.60). We found a three-fold increase in risk of depression among individuals who reported feeling "not very close at all" with family members compared to those who reported feeling "very close" to family (OR = 3.35, 95% CI = 1.81-6.19). CONCLUSIONS: These findings reinforce previous research documenting the important relationship between social support and depression, and perhaps should lead us to reexamine the individualistic models of treatment that are most evaluated in United States. The lack of evidence-based data on support groups, peer counseling, family therapy, or other social support interventions may reflect a majority-culture bias toward individualism, which belies the extensive body of research on social support deficits as a major risk factor for depression. PMID- 22774305 TI - The impact of goal-striving stress on physical health of white Americans, African Americans, and Caribbean blacks. AB - OBJECTIVE: To contribute to the growing understanding of U.S. black-white health disparities by examining psychosocial stress as an important contributor to physical health problems. METHODS: Data are from the National Survey of American Life, an integrated national household probability sample of White Americans, African Americans, and Caribbean blacks. Regression analysis was used to assess associations between goal-striving stress and hypertension, BMI, physical health problems, and self-rated health. RESULTS: After accounting for sociodemographic factors and three additional stressors--personal problems, lifetime racial discrimination, and everyday racial discrimination-goal-striving stress was a significant predictor of hypertension, physical health problems, and diminished self-rated health. Ethnicity moderated the relationship; the negative association between goal-striving stress and physical health problems was strongest for Caribbean blacks. CONCLUSIONS: This study extends the research on goal-striving stress and adds to a growing literature documenting relationships between social processes and disease. PMID- 22774306 TI - Demographic differences in the treatment and control of glucose in type 2 diabetic patients: implications for health care practice. AB - OBJECTIVE: Identifying modifiable covariables that reduce demographic disparities in controlling type 2 diabetes could inform efforts to improve health equity. RESEARCH DESIGN AND METHODS: This retrospective study utilized electronic health record data on 22,285 adults with type 2 diabetes seen at 110 outpatient clinics in the Southeast U.S. from 2004-2008. Demographic differences in diabetes control and modifiable covariables which reduce those disparities were quantified using descriptive and logistic regression analysis. RESULTS: Patients were 55.8 +/- 14.6 (SD) years old, 57.5% women, 61.0% white: 39.0% black and had baseline body mass index 34. +/- .3 kg/ m2 and HbA1c 7.61 +/- 1.9%. The percentage with HbAlc <7% was higher in Whites than blacks (55.6% vs. 44.7%, P < .0001) and rose with age in all patients from 45.3% at <50, to 50.0% at 50-64, and 59.6% at > or =65 years, P < .001. white vs. black race (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.51-1.68) and age/ 10 years (OR 1.20/10 years, 95% CI 1.17-1.22) were predictors of HbAlc <7% in univariable logistic regression. In multivariable analysis, three modifiable covariables (initial HbAlc, therapeutic inertia, visit frequency) accounted for 47.9% of variance in diabetes control. When accounting for these modifiable covariables, the independent impact of race/ethnicity (OR 1.21, 95% CI 1.13-1.30) and age (OR 1.13, 95% Cl 1.11-1.16) on HbA1c control declined. CONCLUSIONS: Race and age-related difference in diabetes control declined significantly when modifiable covariates were considered. Greater attention to early diagnosis and treatment, ensuring regular healthcare visits and overcoming therapeutic inertia could improve diabetes control and health equity. PMID- 22774307 TI - Type 2 diabetes and ethnic disparities in cognitive impairment. AB - OBJECTIVES: We explored whether ethnic differences in type 2 diabetes (T2D) explain ethnic disparities in cognitive impairment. DESIGN: Longitudinal study. SETTING: A cohort study of multiethnic community-dwelling elderly persons in Northern Manhattan, New York. PARTICIPANTS: 941 participants aged > or =65 years without prevalent cognitive impairment or dementia (CID) were followed for a median of 7.1 years. MAIN OUTCOMES MEASURES: CID was defined by a clinical dementia rating > or = .5. CID risk attributable to T2D was estimated for each ethnic group using the hazard ratio (HR) relating T2D and CID and the ethnic prevalence of T2D. RESULTS: 448 participants developed CID; 69 (31.4%) non Hispanic whites (whites); 152 (48.6%) non-Hispanic-blacks (blacks); 227 (55.6%) Hispanics, P < .001. T2D prevalence was 8.2% in Whites, 20.1% in blacks, and 19.6% in Hispanics, P < .001. Controlling for age, sex, education, and APOE E4, the HR relating T2D and CID was 1.63 (95% CI 1.26, 2.09). CID attributable to T2D was higher in blacks and Hispanics compared to Whites (11.4% vs. 4.9%; P = .06). We estimated that reducing the ethnic disparities in diabetes prevalence could reduce the CID ethnic disparities by 17%. CONCLUSIONS: Reducing ethnic differences in T2D prevalence could partially reduce ethnic differences in incident CID. PMID- 22774308 TI - Descriptive profile of people with diabetes who use the Puerto Rico Quitline. AB - OBJECTIVE: To provide a descriptive profile of the people with diabetes (PWD) who received the services of the Puerto Rico Quitline (PRQ) during 2008, compared to non-diabetic people (NDP) to establish a significant statistical difference. METHODS: Using a cross-sectional study methodology, the Quitline database was analyzed. Ninety-four percent of the 1,137 people who received the services of the PRQ during 2008 and completed all the interviews were included in the analysis. Frequency distributions and means calculation were performed to describe the PWD. Chi-square tests, odds ratio, t test and 95% confidence intervals were calculated to identify statistically significant differences between the PWD and NDP. RESULTS: Nearly 11 percent (10.9%) of the people who received the services of the PRQ during 2008 and completed all the interviews reported a diabetes diagnosis. Health conditions were reported by 95.7% of PWD vs. 62.3% of NDP (P < .01). People with diabetes were more likely to have hypertension (P < .01), circulatory problems (P < .01), and respiratory infections (P = .02) than NDP. They also reported a higher mean number of smoking years than the NDP (P < .01), but the PWD were less likely to use menthol cigarettes Sthan NDP (P =.01). A physician's recommendation is the only reason for trying to quit smoking with a statically significant difference between the PWD and the NDP (P = .02). The mean number of alcoholic beverages consumed per day for the PWD was 8 and for the NDP it was 5 (P < .01). CONCLUSION: This study provides important evidence that can help increase the chances of success in the smoking cessation process in the PWD who access the services of the Quitline program. PMID- 22774309 TI - The Latino Health Project: pilot testing a culturally adapted behavioral weight loss intervention in obese and overweight Latino adults. AB - OBJECTIVE: To pilot test a culturally adapted behavioral weight loss intervention in obese and overweight Latino adults. DESIGN: Pilot study. SETTING: Latino community organization in Durham, North Carolina. PARTICIPANTS: Overweight and obese, self-identified Latinos > or =18 years old. INTERVENTION: Intervention consisted of 20 weekly group sessions (90-120 minutes each) incorporating motivational interviewing techniques. The intervention goal was weight loss by adopting the Dietary Approach to Stop Hypertension (DASH) dietary pattern, increasing physical activity, and reducing caloric intake. The cultural adaptation included foods and physical activities commonly used in the Latino culture, using a Spanish-speaking interventionist, and conducting the intervention at a local Latino community organization. MAIN OUTCOME MEASURES: Weight, body mass index (BMI), blood pressure, dietary pattern, and physical activity were measured at baseline and at 20 weeks. RESULTS: A total of 56 participants are included in the final analysis. The average weight loss was 5.1 lbs (95% CI -8.7 to -1.5; P = .006); and there was a reduction in BMI of 1.3 kg/m2 (95% CI -2.2 to -0.5; P =.002) at 20 weeks. Systolic blood pressure decreased by 2.6 mm Hg (95% CI -4.7 to -0.6; P = .013). CONCLUSION: A culturally adapted behavioral intervention for the treatment of overweight and obesity is potentially effective in a diverse group of Latino adults. PMID- 22774310 TI - The relation of acculturation to overweight, obesity, pre-diabetes and diabetes among U.S. Mexican-American women and men. AB - OBJECTIVE: To estimate and compare the prevalences of overweight, obesity, pre diabetes and diabetes among a nationally representative sample of Mexican American, non-Latino white and black adults, and by acculturation for Mexican Americans. DESIGN, SETTINGS AND PARTICIPANTS: The NHANES 1999-2008 data sets were used. Binomial regression models were used to compute prevalence ratios and their respective 95% confidence intervals to assess the relationships of race/ethnicity and acculturation with obesity, overweight, pre-diabetes and diabetes. MAIN OUTCOME MEASURES: Overweight, obesity, pre-diabetes, and diabetes. RESULTS: Mexican Americans had a higher prevalence of overweight than white non-Latinos and Black non-Latinos. Obesity was significantly more prevalent among the most acculturated Mexican Americans but not the least acculturated. In contrast, the least acculturated Mexican Americans had the highest prevalence of overweight. The prevalence of pre-diabetes was higher among Mexican Americans than white non Latinos and black non-Latinos. The most acculturated Mexican Americans had a higher prevalence of diabetes and the prevalence of pre-diabetes was elevated in less acculturated Mexican Americans. In both unadjusted and adjusted models, the less acculturated were significantly more likely to be overweight and significantly less likely to be obese, compared to more acculturated Mexican Americans, and acculturation was not associated with diabetes or prediabetes in adjusted models. CONCLUSION: Our results suggest that obesity was less prevalent among the least acculturated Mexican-Americans but overweight was more prevalent. PMID- 22774313 TI - Exploratory study on the international medical graduate-patient relationship: patient's perceptions of the quality of care delivered by his or her non-native doctor. AB - OBJECTIVE: This study examined the influence of social distance upon the patients' perceptions of the quality of care delivered by their non-native international medical graduates (NNIMGs) in an inner-city primary care residency program. Within the inner city, there is a growing trend of NNIMGs providing health care services, thereby creating a situation of maximal social distance with respect to nativity, race, and socioeconomic status. DESIGN: Two female NNIMG residents, one from India and one from China, were the focus of ten hour long in-depth interviews with patients who participated in this exploratory qualitative research. RESULTS AND CONCLUSIONS: Structural supports, communication processes, and status equalization effects emerged as three self-reported influences on the assessment of care that were particular to their physician's NNIMG status. The physician's NNIMG status seemed to exert a status equalization effect that reduced social distance and subsequently increased the perception of the quality of care. PMID- 22774311 TI - Exploring differences in adiposity in two U.S. Hispanic populations of Mexican origin using social, behavioral, physiologic and genetic markers: the IRAS Family Study. AB - OBJECTIVE: The census classification of Hispanic origin is used in epidemiological studies to group individuals, even though there is geographical, cultural, and genetic diversity within Hispanic Americans of purportedly similar backgrounds. We observed differences in our measures of adiposity between our two Mexican American populations, and examined whether these differences were attributed to social, behavioral, physiologic or genetic differences between the two populations. RESEARCH DESIGN AND METHODS: In the IRAS Family Study, we examined 478 Hispanics from San Antonio, Texas and 447 Hispanics from the San Luis Valley, Colorado. Associations with body mass index (BMI), visceral adipose tissue area (VAT), and subcutaneous adipose tissue area (SAT) using social, behavioral, physiologic and genetic variables were examined. RESULTS: Hispanics of Mexican origin in our clinic population in San Antonio had significantly higher mean BMI (31.09 vs. 28.35 kg/m2), VAT (126.3 vs. 105.5 cm2), and SAT (391.6 vs. 336.9 cm2), than Hispanics of Mexican origin in the San Luis Valley. The amount of variation in adiposity explained by clinic population was 4.5% for BMI, 2.8% for VAT, and 2.7% for SAT. After adjustment, clinic population was no longer associated with VAT and SAT, but remained associated with BMI, although the amount of variation explained by population was substantially less (1.0% for BMI). CONCLUSION: Adiposity differences within this population of Mexican origin can be largely explained by social, behavioral, physiologic and genetic differences. PMID- 22774312 TI - Sex and ethnic differences in validity of self-reported adult height, weight and body mass index. AB - OBJECTIVES: Describe self-reported and measured height, weight, and body mass index (BMI) stratified by sex and ethnicity in the United States, explore ethnic variations in the likelihood of under-reporting BMI, and investigate pathways linking race/ethnicity to the underassessment of BMI. DESIGN: An observational study. SETTING: The entire United States. PATIENTS OR PARTICIPANTS: Data were from the 2007-2008 National Health and Nutrition Examination Survey, a nationally representative sample of non-institutionalized civilian Americans. MAIN OUTCOME: Objectively measured and subjectively reported BMI. MEASURES: Independent variables include race/ethnicity (non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and others), sex, age groups (age 20-29, 30-49, 50-69, and > or =70), marital status (currently married vs other marital categories), education (less than high school, high school graduate or equivalent, some college, college graduate or above), and poverty income ratio (PIR). RESULTS: This study confirmed that the use of reported BMI led to underestimates of the population prevalence of overweight and obesity due to the general tendency towards over-reporting height and under-reporting weight. Women were more likely than men to under report BMI. And whites were more likely than Blacks and Hispanics to under-report BMI. Other factors positively associated with higher likelihood of under reporting of BMI included overweight and obese weight status, aged > or =60 years, and college education. Among women, family income was an additional positive covariate. CONCLUSIONS: The results from this study underscore the need for frequently monitoring ethnic differences in validity of reported BMI and highlight the care which needs to be taken in making comparisons across sociodemographic groups based on reported BMI. PMID- 22774314 TI - Maternal health prior to pregnancy and preterm birth among urban, low income black women in Baltimore: the Baltimore Preterm Birth Study. AB - OBJECTIVES: Black women have increased risk of preterm birth compared to white women, and overall black women are in poorer health than white women. Recent recommendations to reduce preterm birth have focused on preconception health care. We explore the associations between indicators of maternal prepregnancy health with preterm birth among a sample of black women. DESIGN: The current study was prospective. SETTING: Enrollment occurred in prenatal clinics in Baltimore. PARTICIPANTS: Women (N=922) aged > or =18 were enrolled in the study. Data on maternal health, behaviors, and pregnancy outcome were abstracted from clinical records. MAIN OUTCOME MEASURE: Logistic regression was used to evaluate associations between behavioral and health status variables with preterm birth. RESULTS: In bivariate analysis, alcohol use, drug use and chronic diseases were associated with preterm birth. In the logistic regression analysis, drug use and chronic diseases were associated with preterm birth. CONCLUSIONS: These results demonstrate an association between maternal health and behaviors prior to pregnancy with preterm birth among black women. Providing access to health care prior to pregnancy to address behavioral and health risks may improve pregnancy outcomes among low-income black women. PMID- 22774316 TI - Characterization of clinical study populations by race and ethnicity in biomedical literature. AB - OBJECTIVE: The importance of race and ethnicity in biomedical research has long been a subject of debate, recently heightened by data revealed by the completion of the sequencing of the human genome and the mapping of human genetic variation. We aimed to determine whether and how the reporting of race has changed over the last three decades and how the practice may differ given study location, where the journal of publication is based, and decade of publication. DESIGN: We analyzed a sample of studies published in the Journal of the American Medical Association, The Lancet, and the Canadian Medical Association Journal from 1980 to 2009. MAIN OUTCOME MEASURES: The number of articles that reported race by journal and decade and the descriptors used. RESULTS: Of 1867 articles analyzed, 17.30% reported race. The reporting of race and number of populations reported increased over time for all three journals. In addition, the diversity of race/ethnicity descriptors increased, with increased use of race/ethnicity combinations and nationality of research subjects. CONCLUSION: Though it has increased over the past few decades, the reporting of race/ethnicity of study populations is relatively low, ambiguous and inconsistent, likely influenced by the uncertain relevance of these variables to the study's outcomes, study location, researcher views, and the policies of journals and funding agencies. Thus, due to the inconsistent and ambiguous practice of reporting race/ethnicity, comparison of study outcomes can result in misleading conclusions. Improvements in standardization of terms and new approaches to characterize research participants related to race/ethnicity are imperative. PMID- 22774315 TI - Racial and ethnic disparities in lifetime risk of corpus uterine cancer: a comparative study of Puerto Rico and the United States SEER population. AB - BACKGROUND: Corpus uterine cancer is the most common gynecologic malignancy in Puerto Rico and the United States. METHODS: We assessed the lifetime risk of developing and dying of corpus uterine cancer in women living in Puerto Rico (PR) and among Hispanics, non-Hispanic whites (NHW), and non-Hispanic blacks (NHB) in the United States. Data from the PR Central Cancer Registry and the Surveillance, Epidemiology, and End Results program were analyzed from 1993-2004. RESULTS: In PR, the probability of developing corpus uterine cancer increased from 1.21% in 1993-1995 to 1.69% in 2002-2004. The probability of developing this malignancy from 2002-2004 was 1.59% for NHB, 1.80% for Hispanics and 2.54% for NHW. The ratio of estimated probabilities only showed significant lower risk in PR as compared to NHW (.67, 95% CI = .59-.74). The probability of dying from corpus uterine cancer during 2002-2004 was .47% for Hispanics, .49% for NHW, .53% for PR and .76% for NHB. The ratio of estimated probabilities only showed significant lower risk of death in PR as compared to NHB (.70, 95% CI = .54-.85). CONCLUSIONS: The lifetime risk of developing corpus uterine cancer has increased in PR, suggesting higher exposure to risk factors in this population. Despite the lower lifetime risk of this malignancy in PR as compared to NHW, the similar lifetime risk of death in these groups suggests a disparity that may be influenced by differences in disease etiology and/or access or response to treatment. Assessment of risk factors, in addition to access to health services, is required to further understand these patterns. PMID- 22774317 TI - Biochemical differences in ethnic groups in Durango, Mexico. AB - OBJECTIVE: The aim of this study was to assess biochemical differences between Tepehuano indigenous people, and Mennonite and Mestizo populations of Durango, Mexico. METHODS: Our study involved 334 volunteers aged 15 to 80 years; 132 Mennonite and 130 Mestizo individuals from Nuevo Ideal Municipality and 72 Tepehuano indigenous people from Mezquital Durango were evaluated. A clinical history and fast determination of aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid, urea and creatinine were performed on each studied case. RESULTS: Statistically significant differences between the three studied groups were found for age, weight and height (P < .05), with higher values observed in men. The highest plasma urea levels were found in Mennonite compared to Mestizo people, followed by the Tepehuano indigenous. Higher biochemical parameters were found in men (vs women) in the studied groups. The percentage of individuals with abnormal levels for AST, ALT and uric acid were higher in Tepehuano indigenous people than in Mestizo, whereas the urea and creatinine percentages were higher in Mestizo people. CONCLUSION: The differences found on biochemical tests, could be explained by differences in lifestyle such as diet and sanitary habits. PMID- 22774318 TI - Total vascular risk as a strong correlate of severity of diabetic peripheral neuropathy in Nigerian Africans. AB - OBJECTIVES: HbA1c, commonly utilised in Caucasian studies, is an inconsistent risk marker for the severity of diabetic peripheral neuropathy (DPN) severity. Other vascular risk factors have been shown to affect DPN. However, no study has examined the relative impact of HbA1c and total cardiovascular risk load (TCRL) on DPN severity. Using the United Kingdom Prospective Diabetes Study cardiovascular risk engine as a measure of TCRL, we sought to determine if TCRL is a better correlate of DPN severity than HbA1c alone. METHODS: We studied 277 consecutive consenting black type 2 diabetes mellitus (DM) patients in Nigeria. We defined DPN using Michigan Neuropathy Screening Instrument thresholds defined by prior validation studies. Severity of DPN was measured using the modified Dyck's grading, which had been previously validated in Nigeria. Patients with non diabetic causes of neuropathy were excluded. RESULTS: 197 (71.1%) patients had DPN. The mean HbA1c value was 6.9%. The HbA1c correlated significantly to the fasting plasma glucose (r = .36), but did not correlate significantly to the DPN severity (P = .304, rho = .075). The TCRL had the strongest significant correlation to DPN severity (P = < .001, rho = .285). Age and dyslipidemia, which are also components of the TCRL, emerged as independent statistical predictors of DPN severity in multivariate analysis. CONCLUSIONS: In Nigerian Africans, TCRL was a stronger statistical correlate of DPN severity than HbA1c. In the setting of multiracial studies, the development of a special risk engine for monitoring the risk of DPN is recommended as a substitute for HbA1c alone. PMID- 22774319 TI - Leading to a future of better health and health care for Tennesseans. PMID- 22774320 TI - Is bedside manner or technical expertise more important? PMID- 22774321 TI - That pivotal moment. PMID- 22774322 TI - Safe and effective pain management in elders. AB - The elderly are often either untreated or undertreated for pain. The consequences of undertreatment for pain can have a devastating impact on health and quality of life, resulting in depression, anxiety, social isolation, cognitive impairment, immobility, and sleep disturbances. Reasons cited by healthcare professionals for inadequate pain control include lack of training, inappropriate pain assessment, and reluctance to prescribe opioids, however, the undertreatment of pain can be legally considered to constitute neglect, abuse, or negligence. The appropriate treatment of pain is humane and with good diagnostic efforts, proper consideration of appropriate medications and monitoring for adverse effects, healthcare providers can help to successfully control pain. PMID- 22774323 TI - Comparison of load-fatigue performance of posterior ceramic onlay restorations under different preparation designs. AB - OBJECTIVE: The objective of this study was to evaluate the load-fatigue performance of posterior ceramic onlay restorations relative to two variables: preparation design (with or without buccal veneers); and the existing amount of tooth structure (non-worn tooth, worn tooth). METHODS: Sixty extracted third molars were divided into five groups. One group received a mesial-occlusal-distal (MOD) gold onlay restoration (control). The other four experimental groups were prepared for ceramic onlay restorations. Two of the groups additionally received 2-mm occlusal reduction to simulate occlusal wear. All restored teeth were subjected to thermocycling prior to fatigue testing. A fatigue load of 150 N was applied on the occlusal surface at a frequency of 1.2 hz, at an angle of 135 degrees to the long axis of the tooth. Specimen failure was defined as the occurrence of crack propagation in the luting cement layer. This was monitored by the strain gauge on the specimen. RESULTS: All specimens restored on worn tooth had significantly lower fatigue failure cycle counts than those of non-worn tooth. The fracture mode analysis revealed that ceramic fracture tended to be demonstrated only in the group of worn tooth groups. CONCLUSIONS: The addition of a buccal veneer component had no significant effect on the load-fatigue performance of posterior ceramic onlay restorations, but the existing amount of tooth structure did have a significant effect on the load-fatigue performance of posterior ceramic onlay restorations. Catastrophic failures (ceramic fracture) occurred only in the group of worn tooth. PMID- 22774325 TI - A clinical investigation of the Rescue internal implant. AB - INTRODUCTION: Immediate implant placements in molar sites have been problematic. This report describes the use of a novel dental implant placed immediately in first and second molar sites. METHODS: Implants were inserted for 19 patients in molar sites immediately after tooth extraction. Patients were followed for 1 year post-insertion, with radiographs obtained and periodontal parameters recorded every 6 months. RESULTS: The implant success rate was 95.24%. Esthetics generally was acceptable in the posterior quadrants. Crestal bone die-back in most cases only extended to the crest of the implant. The periodontal parameters recorded at the 6- and 12-month recalls were consistent with periodontal health. CONCLUSIONS: Use of this novel implant system can be successful if the guidelines for its use are followed. It is best utilized by experienced implantologists. PMID- 22774326 TI - Patient communications in the digital age. PMID- 22774324 TI - Innovations for combating dentin hypersensitivity: current state of the art. AB - Dentin hypersensitivity is a common dental complaint, and in severe cases it can impair eating, drinking, and even speaking, thus interfering with the normal daily life of an individual. Throughout years of research, there has been significant advancement in understanding dentin hypersensitivity, and various treatment regimens have been developed for combating the problem. The continued efforts have recently resulted in a novel technology that uses 8% arginine and calcium carbonate for treating dentin hypersensitivity. Formulations of oral care products using this technology--including toothpaste and prophylactic pastes- have demonstrated not only their effectiveness but also their ability to provide instant relief. This paper provides an overview of the etiology of dentin hypersensitivity, the discovery and development of measures for combating the problem, and the available data on the clinical efficacy of products based on 8% arginine and calcium carbonate. PMID- 22774327 TI - The AHA scientific statement on periodontal disease and ASVD: how should clinicians respond? PMID- 22774328 TI - Proactive intervention dentistry: a model for oral care through life. AB - Tools and techniques are available to oral care providers that have been found to be effective in reversing and controlling the caries process. In addition to fluoride, these tools include new remineralization therapies that can be incorporated into solutions, creams, and dentifrices, and bioactive restorative materials that work effectively with dental hard tissues. By incorporating such "proactive interventions" into their practice and educating patients on maintaining a daily oral hygiene regimen, clinicians can inhibit the multifactorial disease process of demineralization and caries before more extensive treatment becomes necessary. PMID- 22774329 TI - The oral-medical disease connection: pregnancy, cardiovascular disease, and diabetes. AB - There is considerable perplexity regarding the oral-systemic connection. Existing research, including epidemiologic findings, interventional studies, and a smaller number of reports seeking to elucidate mechanisms of action, have been somewhat contradictory. Of importance to the practicing clinician is how to gain understanding of this abundance of emerging scientific evidence, synthesize it, and integrate it into clinical practice. In essence, clinicians need to be able to authoritatively respond to their patients' inquiries regarding relationships between oral and systemic disease. This article seeks to provide insights to this issue with regards to pregnancy, cardiovascular disease, and diabetes. PMID- 22774330 TI - Enhancing extraction socket therapy with a biphasic calcium sulfate. AB - Studies have shown that tooth extraction results in loss of bone volume, which compromises dental implant placement. Prevention of site collapse at the time of extraction is recommended. In this 4-month case series, 40 patients were treated with an innovative biphasic calcium sulfate graft, demonstrating its ability to preserve or augment socket volume and resorb in the time period desired between extraction and implant placement. Some representative samples were retrieved at the time of implant placement and evaluated histologically and morphometrically for vital bone formation. PMID- 22774331 TI - Cosmetic concerns provide opportunity for comprehensive dentistry. AB - This case involved a woman with occlusal dysfunction who was dissatisfied with her smile because of the unsightly display of gold crowns in her posterior and unattractive mottling on her anterior teeth. Factors such as a significant history of clenching and grinding, the management of active disease and infection, and the patient's desire for an ideal or "media-generated" smile increased the difficulty of the case. As part of a comprehensive restorative plan that included disease control treatment, root canal therapy, and orthodontics to idealize tooth positioning, a Kois deprogrammer was used to evaluate the patient's increasingly symptomatic, unacceptable function. In addition to reducing functional and biomechanical risks, the case resulted in improved esthetics with which the patient was highly pleased. PMID- 22774333 TI - Bright future ahead for 3M ESPE curing lights. PMID- 22774332 TI - High demand for composites a driving force for curing light advancements. PMID- 22774334 TI - CAO Group's curing lights deliver ergonomics, controlled power. PMID- 22774336 TI - Versatility, durability are hallmarks of Ultradent's VALO curing lights. PMID- 22774335 TI - Ivoclar Vivadent's bluephase style offers clinicians convenience, comfort. PMID- 22774337 TI - A direct technique for fabricating esthetic anterior fixed provisional restorations using polycarbonate veneers. AB - Fabrication of esthetic interim restorations by a chairside technique often challenges the clinician with regard to the required time and skills, as well as meeting the expectations of the patient. Autopolymerizing polymethyl methacrylate resin has been reported to be the most popular material for fabricating provisional restorations. However, this material does not routinely yield esthetic provisional restorations via a chairside technique. This article describes a simple technique to overcome some of the disadvantages of this material by using prefabricated polycarbonate facings backed with autopolymerizing acrylic resin. This technique can be used chairside for fabricating esthetic anterior interim restorations, utilizing the beneficial properties of both materials. It exploits the manufactured smooth-surface finish, superior esthetics, color stability, and durability of polycarbonate facings, as well as the marginal adaptation, strength, and low cost of autopolymerizing acrylic resin. PMID- 22774338 TI - For survivors, the battle has been hard but the triumphs are frequent. PMID- 22774339 TI - Survivorship wellness: as survivors live longer, care focuses on long-term wellness. PMID- 22774340 TI - How do you use running to raise awareness of cancer survivorship? PMID- 22774341 TI - Pamphlet may help patients with breast cancer learn about treatment-focused genetic testing. PMID- 22774342 TI - The case of the harrowing hot flashes. PMID- 22774343 TI - ONS reaches out to CMS about clinical trial access. PMID- 22774344 TI - How far has the war on cancer come in the past 40 years? PMID- 22774345 TI - Cancer cell line encyclopedia will help researchers match drugs to patients in clinical trials. PMID- 22774346 TI - Successful associations are volunteer led, staff run. PMID- 22774347 TI - Doing the simple things well. PMID- 22774348 TI - A conversation about practice development and knowledge translation as mechanisms to align the academic and clinical contexts for the advancement of nursing practice. AB - Practice development (PD) and knowledge translation (KT) have emerged recently as methodologies which assist advancement in gathering and using evidence in practice. For nursing to benefit from these methodologies there is a need to advance the dialogue between academia and the service sector concerning the use and further development of these methodologies as well as how we create the most effective partnerships between academia and practice. To advance this dialogue and to gain insights into the similarities and differences between KT and PD and between the academic and the service sectors, four conversations from different leaders in these sectors have been gathered and are presented here. These four discrete narratives are presented to showcase the diversity of sector contexts in relation to PD and KT methodologies. Narrative One focuses on some of the theoretical and policy issues related to creating partnerships between traditional "knowledge creation systems" (universities) and "knowledge utilization systems" Narrative Two discusses how a large school of nursing responded to the challenge of creating partnerships for practice development in an attempt to bridge the academic/service divide and produce benefits to both organisations. Narratives Three and Four describe the view of practice development from the service side. The final section of the paper presents an agenda for discussion and action based on the emerging set of principles. PMID- 22774349 TI - High fidelity patient silicone simulation: a qualitative evaluation of nursing students' experiences. AB - Clinical experience is recognised as a source of fear and anxiety for undergraduate nursing students. Simulated learning experiences have been identified as potentially increasing confidence, however most techniques do not always reflect clinical reality or are too costly. The aim of the current study is to explore nursing students' perceptions of the use of High Fidelity Silicone Simulation, developed by one university academic to overcome these limitations. A simulated patient with a personal and medical history is developed and brought to life through wearing life-like silicone props including face, hands and torso. The academic is able to adapt responses to direct student learning. This paper presents the findings from a qualitative exploratory study of nursing students' responses to this technique. Twenty-one students in second or third year of the nursing program participated in one of three focus groups to discuss their experiences. Data were analysed using a thematic approach. Data analysis revealed three main themes: preparation for clinical reality, reducing fear/increasing confidence, and taking out of comfort zone. These findings suggest that this technique has the potential to increase nursing students' sense of preparedness for their clinical experience, thus reducing the negative impact of fear and apprehension. PMID- 22774350 TI - The management of behavioural problems associated with dementia in rural aged care. AB - BACKGROUND: In Australia 60-80% of all residents in aged care facilities have a cognitive impairment related to dementia with this figure predicted to increase. The associated behavioural and psychological disorders associated with dementia frequently result in the prescription of antipsychotic drugs to assist in limiting disruptive or concerning unmet needs behaviour. Antipsychotic prescription rates in aged care facilities are estimated to be as high as 80% despite the well known adverse effects in this population. Person centred care approaches to management of behavioural and psychological symptoms of dementia (BPSD) has not been widely implemented despite its reported effectiveness. Other interventions aimed at reducing antipsychotic use in aged care has been limited and the barriers to the use of non pharmacological strategies are poorly researched. METHODOLOGY: In this study a 43 point questionnaire was distributed to 6 rural aged care facilities to assess nurses' knowledge of non pharmacological and pharmacological interventions, and the frequency, perceived barriers and efficacy of both strategies. Resources and information bases utilised in behaviour management was also explored. FINDINGS: The results indicated that staff have a good knowledge of possible underlying causes of BPSD, but a poor understanding of appropriate methods of management and resources available to assist them. Time constraints were frequently cited by respondents as problematic in managing behavioural problems. The results of this study suggest the need for utilisation of tools to assist nurses to identify target behaviours, implementation of appropriate management and access to the resources available. PMID- 22774351 TI - Supporting rural and remote area nurses to utilise and conduct research: an intervention study. AB - BACKGROUND: Nurses are expected to embrace research and evidence-based practice but in rural/remote facilities it is particularly difficult to develop and utilise research skills. OBJECTIVES: This collaborative study aimed to explore nurses' orientation to research and address known inhibitors to engagement with research in rural/remote north Queensland locations. PARTICIPANTS: The sample comprised nurses from two rural/remote areas within a regional health service. Methods A pre-test post-test intervention study with two levels of data collection: responses to Edmonton Research Orientation Scale administered 3 times to all nurses, and number of research proposals developed. This intervention comprised provision of face-to-face workshops, paper-based resources, and informal videoconference, email and telephone contact. RESULTS: Survey response rates varied from 56% to 34%. Two-thirds of respondents were over 40 years old; 75% were Registered Nurses. One quarter rated understanding of journal articles as poor or very poor and 50% rated their knowledge of research similarly. However, 50% said research had changed the way they practiced. Older nurses, nurses with tertiary qualifications and those with senior appointments had more positive orientation to research scores. Several locally relevant research proposals were developed from one site; two received internal funding for further development and implementation. The intervention also led to increased utilisation of library resources which has continued past this study's end. CONCLUSIONS: The variation in uptake between sites reinforces the need for locally targeted support. This study has gone beyond measuring research utilisation by including evaluation of support mechanisms to engage nurses in developing research proposals. PMID- 22774353 TI - Celebrating 25 years of excellence and professional connectedness: the Association of Black Nursing Faculty. PMID- 22774352 TI - Change for the better: an innovative model of care delivering positive patient and workforce outcomes. AB - OBJECTIVE: To evaluate patient and workforce outcomes following the implementation of the Practice Partnership Model of Care. DESIGN: Pre-test-post test design. SETTING: A 29-bed surgical ward at a tertiary-level regional hospital. SUBJECTS: Summary de-identified data from all patients and ward nursing staff in the study period. INTERVENTIONS: The Practice Partnership Model of Care has four main components: working in partnership; clinical handover at the bedside; comfort rounds; and environmental modifications. These reflect patient centered and quality focused initiatives and use a total quality improvement framework that aims to transform care at the bedside. MAIN OUTCOME MEASURES: Patient outcomes: changes in patient safety (measured by numbers of medication errors and patient falls); satisfaction with care (use of the call bell system, number of complaints and compliments). Workforce outcomes: changes in staff satisfaction (measured through staff sick leave). RESULTS: A statistically significant reduction in use of nurse call bells (p=<0.001) post-implementation. Medication errors and patient falls reduced, with an overall reduction of 4% in staff sick leave. CONCLUSIONS: The Practice Partnership Model of Care positively affected patient and workforce outcomes, suggesting further exploration of this model in other hospital contexts is warranted. PMID- 22774354 TI - The nurse faculty shortage. PMID- 22774355 TI - Systematic review of the literature on simulation in nursing education. AB - Simulation-based learning is an educational intervention which creates an environment that is conducive to experiential learning. Despite the prevalence of research on the influence of simulation on nursing education, there is a dearth of literature on the effectiveness of simulation-based learning. This systematic review examines literature on simulation outcomes in nursing education from the years 2000-2010. The electronic databases reviewed for the systematic review of the literature included: CINAHL Plus, Medline, Health Source: Nursing/Academic Education, Google Scholar, and Digital Dissertations and Theses through ProQuest. The MeSH search terms included "simulation outcomes measurement" and "nursing education". Seventeen studies were included in the review of the literature. The literature was categorized into three themes; internal outcomes, external outcomes, and clinical evaluation. The available literature on simulation and nursing education provides evidence that that simulation is useful in creating a learning environment which contributes to knowledge, skills, safety, and confidence. This systematic review of the literature revealed a gap in the literature pertaining to the transfer of these outcomes to the clinical setting, and lays a foundation for further research on outcomes specific to simulation and nursing education. PMID- 22774356 TI - African American present perceptions of organ donation: a pilot study. AB - PURPOSE: The purpose of this pilot research project is to explore each of the five general areas of reluctance associated with organ donation among African Americans. These areas include: (1) a lack of awareness, (2) lack of trust by the medical profession, (3) fear of premature death, (4) discrimination, and (5) religious beliefs and misconceptions. Strategies will be explored that may help dispel the misconceptions about organ donation, and, at the same, increase awareness of the need for African Americans to become organ donors. METHOD: A culturally sensitive 10-item survey was administered online to 70 African Americans to identify their perceptions about the five concerns related to participation in the organ donation program. Participants were recruited from clergy and sororities. RESULTS: Of the 70 African Americans who were sent the survey, 55 of the respondents completed the survey to yield a 78.6% rate of return. Most participants reported having some reservation concerning organ donation, and many of them reported that their reservations were related to their mistrust of the medical profession. CONCLUSION: The perceptions of African Americans concerning organ donation remain an issue. The 5 areas of reluctance remain at the forefront for decision making in terms of becoming an organ donor. Continued education is needed in order to help dispel these issues. PMID- 22774357 TI - Partnering with the black church: recipe for promoting heart health in the stroke belt. AB - Health disparities related to cardiovascular disease (e.g., heart disease, high blood pressure, diabetes, and stroke) have remained higher in the African American community than in other populations. African Americans living in the stroke belt are at an even higher risk for these conditions. Recently, increasing numbers of health agencies and researchers have successfully partnered with the black church to respond to the troubling statistics regarding these health disparities. Because the black church has a long history of being in the forefront of addressing critical social, economic, political, and health issues of African Americans, it is clear they are the principal gatekeepers in reversing these negative health trends. Working with churches to reduce cardiovascular disease is not a new concept. Hypertension screening programs were established at churches approximately 30 years ago. This article shares findings of elements to improve relations between community agencies and pastors, explores the strengths and challenges of working with churches, examines the role of the pastors in establishing successful programs, and identifies model programs. This article will identify key factors that are essential to cardiovascular health programs that purport to reach high-risk populations for cardiovascular disease with life saving environmental policies and behavior change strategies. Suggestions are provided for working with pastors, churches, and church resources to maximize the desired outcomes of future health promotion interventions. Examples of strategies include serving healthier choices during church meals; the inclusion of relevant scriptural citations in promotional materials; the implementation of instruction, training, and exercise programs; and, the provision of tangible compensation to the churches and congregants facilitating the health initiatives. PMID- 22774359 TI - "Lansley must listen to nurses on the front line". PMID- 22774358 TI - Visiting the USSR: a trip of a lifetime. AB - To Russia, who me? That is actually how it all began. A decade or more ago, I had the opportunity to visit what was then known as the Union of Soviet Socialist Republics (USSR), Russia. Although, this place held high priority on my list of places to go, I never thought such a trip was within my reach. This idea was quite fascinating to me because of the events that did happen there, including the Russian space ship Sputnik and the dog, the high stepping military officers, Red Square and the St. Basil's Cathedral. After reading a lot about Russia, I thought it would be great to see a clean place, where it was unlawful to throw paper on the streets, and ride in public transportation such as the buses, taxis and the subway system, which were immaculately clean. It was an exciting trip, one, I will always remember, but would be a difficult adjustment to make, to live. PMID- 22774360 TI - Fury over steep rise in NMC fees... PMID- 22774361 TI - "We must develop leaders in learning disability nursing". PMID- 22774362 TI - "See the big picture and stay vigilant over patient safety". PMID- 22774363 TI - Medication errors in patients with dysphagia. AB - BACKGROUND: The administration of medicines to patients with dysphagia is complex and prone to errors. AIM: To determine the medicine administration error (MAE) rate for those with dysphagia in acute hospitals. METHOD: Data was collected on the preparation and administration of oral medicines to patients with and without dysphagia, including those with enteral feeding tubes, using direct observation of 65 nurse-led medicine administration rounds at four acute general hospitals. RESULTS: Excluding time errors, the normalised frequency of MAEs for patients with dysphagia was 21.1% compared with 5.9% for those without the condition. CONCLUSION: The increased MAE rate in patients with dysphagia means extra care is needed when prescribing, dispensing and administering medicines to this group. PMID- 22774364 TI - Drug administration guides in dysphagia. AB - BACKGROUND: Patients with dysphagia are more likely to suffer medication administration errors than those without swallowing difficulties. AIM: To evaluate the use of individualised medication administration guides (I-MAGs) for patients with dysphagia on one stroke ward over six months. METHOD: A specialist pharmacist in dysphagia designed a software package supported with data on national guidelines on administering medicines to this group, which enabled the pharmacist to create I-MAGs. Once the pilot was completed, a questionnaire was given to all nurses, pharmacists and speech and language therapists who had used the guides. RESULTS: Of 26 health professionals approached, 19 returned questionnaires. Eight (62%) nurses felt more confident in their practice when I MAGs were in place. CONCLUSION: I-MAGs were well received and supported individualised care. However, they needed additional pharmacist input and greater nursing time. Research to determine the guides' cost-effectiveness is needed. PMID- 22774367 TI - The appliance of science. PMID- 22774365 TI - Preparing leaders for safeguarding children. AB - The purpose of child safeguarding is to identify children at risk of abuse or neglect and to reduce this risk. NHS trusts are required to have named and designated safeguarding children clinicians, who need strong leadership skills. This article presents the design and implementation of a leadership training programme developed for these professionals, and an evaluative research study of the programme. PMID- 22774368 TI - Using clinical practice as the basis for research. PMID- 22774366 TI - Preventing malaria in travellers: an overview. AB - Malaria is a common, potentially fatal infection found in more than 100 countries. Nurses play an important role in advising travellers about the risk of malaria, methods of prevention and in recognising the disease in returning travellers. This article provides an overview and outlines key areas of knowledge that are essential for nurses involved in giving pre- and post-travel malaria advice. PMID- 22774369 TI - The 12 points of the dental law. PMID- 22774370 TI - Grow your practice using social media: if you aren't online, do patients know you exist? PMID- 22774371 TI - Patient communication goes beyond flossing. PMID- 22774372 TI - When do you need an informed consent form? PMID- 22774374 TI - It's never too early to develop good habits. PMID- 22774373 TI - Volunteers wanted: CommunityHealth clinics look to expand services following grant from Cook County. PMID- 22774375 TI - The fox circling the hen house isn't a mid-level provider. PMID- 22774376 TI - Reducing deaths from smoking. PMID- 22774377 TI - Identifying patients at risk of perinatal mood disorders. AB - Perinatal mental illness influences obstetric outcomes, mother-baby interactions and longer term emotional and cognitive development of the child. Psychiatric disorders have consistently been found to be one of the leading causes of maternal deaths, often through suicide. Postnatal depression and puerperal psychosis are two disorders most commonly associated with the perinatal period. The most efficient strategy to identify patients at risk relies on focussing on clinically vulnerable subgroups: enquiries about depressive symptoms should be made at the usual screening visits. Attention should be paid to any sign of poor self-care, avoidance of eye contact, overactivity or underactivity, or abnormalities in the rate of speech. Particular care should be taken to ask about suicidal ideation and thoughts of harming others, including the baby. One of the most important risk factors is a previous history of depression. The degree of risk is directly correlated with severity of past episodes. Both antenatal and postnatal depression are being increasingly recognised in men. Puerperal psychosis is rare (1 to 2 per 1,000). Sixty per cent of women with puerperal psychosis already have a diagnosis of bipolar disorder or schizoaffective disorder. Women with a personal history of postpartum psychosis or bipolar affective disorder should be considered as high risk for postpartum psychosis. All pregnant women who are identified as being at high risk should have a shared care plan for their late pregnancy and early postnatal psychiatric management. Women with current mood disorder of mild or moderate severity who have a first degree relative with a history of bipolar disorder or postpartum psychosis should be referred for psychiatric assessment. PMID- 22774378 TI - Primary care management of patients who self-harm. AB - Self-harm is best defined as 'any act of self-poisoning or self-injury carried out by an individual irrespective of motivation'. With a 10.5% lifetime risk, self-reported self-harm is common in the community. Self-harm can occur at any age but is most common in young people. Prior self-harm is the key risk factor both for repeated self-harm and also for subsequent suicide. The presence of depressive symptoms predicts repeated self-harm, as does any history of psychiatric illness. Assessment of self-harm (actual or planned) should include: details of preplanning; final acts; the event itself; what happened afterwards; as well as broader psychosocial risk factors. Patients should be asked to reflect on the episode to consider whether they regret it, or whether they are likely to repeat it. Patients should be screened for depression, anxiety, psychosis and history of self-harm. Physical illness and substance misuse increase risk. Referral to secondary care community mental health teams should be considered for patients who present in primary care with a history of self-harm and a risk of repetition. Patients with continuing thoughts or serious intent of self-harm, where supportive or protective factors cannot be identified, may need urgent referral to secondary care. Prediction of further episodes of self-harm is difficult. Some clinicians may find the use of standardised rating scales, such as the SAD PERSONS scale, a useful way to identify patients who warrant referral and further assessment. The GP should provide long-term continuity of care, and maintain a holistic awareness of a patient's life events enabling discussion of the patient's emotional problems at an early stage with the aim of intervening before a crisis. PMID- 22774380 TI - Scalp and hair conditions. PMID- 22774379 TI - GPs have key role in helping patients to stop smoking. AB - Eighteen per cent of all deaths in adults aged 35 or over in England are still attributable to smoking. Almost all these premature deaths could be avoided if smokers stopped before their mid-thirties but only a quarter of people who have ever smoked regularly manage to quit by this age. Advice from the patient's GP is one of the most important triggers to a smoker making an attempt to quit. All patients attending a surgery for any reason who have smoked within the past three years should be offered advice on stopping smoking. Smokers without smoking related diseases are just as likely to respond to advice as those with them. It is also important to re-assess the status of former smokers who were recorded as having stopped within the past three years. Half of those who stopped six months ago will relapse at some point as will 40% of those who stopped a year ago. Offer help with stopping to all smokers. The National Centre for Smoking Cessation and Training has launched a new online training module on how GPs can best deliver smoking cessation support to their patients. Optimum treatment involves behavioural support plus one of the smoking cessation medications. Behavioural support includes a number of specific behaviour change techniques that enhance the smoker's chances of remaining abstinent. These include: measurement of carbon monoxide in expired air; advice on best use of medication and helping smokers to put in place a clear 'not a puff' rule. PMID- 22774381 TI - Therapeutic use of mud. 1912. PMID- 22774382 TI - Nursing home patients are falling through the net. PMID- 22774383 TI - Characterization of metabolically unhealthy overweight/obese African American women: significance of insulin-sensitive and insulin-resistant phenotypes. AB - BACKGROUND: Obesity is often associated with high cardiovascular disease risk factors. Obesity is common in African American women. We investigated the characteristics of metabolically healthy and metabolically unhealthy overweight/obese African American women based on the presence of insulin resistance. MATERIALS/METHODS: We studied 196 apparently healthy overweight/obese African American women with family history of type 2 diabetes. Waist circumference, fasting glucose, insulin, c-peptide, lipids and lipoproteins, and systolic and diastolic blood pressure were obtained in each subject. In addition, insulin sensitivity was calculated using Bergman's Minimal Model Method. We defined insulin-sensitive metabolically healthy African American women as individuals with insulin sensitivity greater than 2.7 x 10(-4) x min(-1) (uU/ mL)(-1) and insulin resistant, metabolically unhealthy as insulin sensitivity less than 2.7 x 10(-4) x min(-1) (uU/mL)(-1). RESULTS: Thirty-three percent of our subjects were metabolically healthy African American women, while 67% were metabolically unhealthy African American women. The metabolically healthy subjects were significantly younger and less obese than the metabolically unhealthy subgroup. Mean fasting serum glucose, insulin, and c-peptide were significantly lower (P = .001) in the metabolically healthy than in metabolically unhealthy subjects. However, the mean blood pressures were within normal in both subgroups. Mean serum cholesterol (p < .05) and triglyceride (p < .001) levels were significantly lower, whereas high-density lipoprotein cholesterol (p < .03) was significantly higher in the metabolically healthy than in the metabolically unhealthy subjects. We found 25.5% of our subjects had metabolic syndrome (30.3% metabolically unhealthy and 15.6% metabolically healthy). CONCLUSION: We concluded that: (1) despite obesity, metabolically healthy African American women appear to be less prone to type 2 diabetes and cardiovascular disease and (2) in view of the higher prevalence of metabolic syndrome, metabolically unhealthy African American women should be targeted for primary prevention of type 2 diabetes and cardiovascular disease. PMID- 22774384 TI - Association of hypertension and bone mineral density in an elderly African American female population. AB - BACKGROUND: Recent studies have shown that hypertension is inversely correlated with bone mineral density (BMD) as determined by dual energy x-ray absorptiometery (DXA) in different ethnic groups. But in most published studies, either the sample size was small or the study was limited by different measurement methods. These limitations leave this association controversial and inconclusive. The current study utilizes a sample of African American females referred for clinical screening of osteoporosis in our center to find out if any association of high blood pressure and BMD in this ethnic group exists. The secondary endpoint was to determine the effect of thiazide diuretics on BMD of the elderly African American females because, theoretically, thiazides are considered to have a positive impact on BMD. METHODS: In this retrospective, cross-sectional study, 10 years of data were reviewed from 1113 medical records of African American females aged 65 years and older whose BMD values were measured by DXA at the lumbar spine (L1-L4) and both femoral necks (the standard sites for BMD determination) along with their T scores and Z scores (used to determine osteopenia vs osteoporosis). Our exclusion criteria included patients who: (1) were current smokers, (2) had a previous oophorectomy, (3) had a history of corticosteroid use, (4) had a history of biphosphonate use, (5) were on hormone replacement therapy, and (6) were diabetic and taking either pioglitazones or roziglitazones. A total of 148 patients were excluded from the analysis due to either incomplete data or exclusion criteria. The remaining sample was then divided into 2 groups based on their hypertensive status. For the subanalysis, the hypertensive group was further divided into 2 additional groups based on their thiazide usage. RESULTS: We had complete data on 965 participants, of which 631 (65.3%) had a history of hypertension and 334 (34.7%) did not. Out of 631 hypertensive patients, 173 were found to be using thiazide diuretics as antihypertensive medication, while 458 were without thiazide diurectic use. The proportion of patients with both osteopenia and osteoporosis was similar in those with and without hypertension (50% vs 50%, p = .95 for osteopenia; 18% vs 19%, p = .95 for osteoporosis). There was no significant difference between the BMD at the lumbar spine, and right and left femoral necks between patients with and without hypertension. This lack of association held true when comparing the mean T scores and Z scores at the above sites. Within patients with a history of hypertension, there were no significant differences in the BMD, T score or Z score at any site with and without a history of thiazide diuretic use. CONCLUSION: Hypertension in elderly African American females aged at least 65 years was not found to be correlated with low BMD at either the lumbar spine (L1 L4) or both femoral necks when confounding factors were taken into consideration. Mean BMD of the hypertensive cohort taking thiazide diuretics was found lower at the lumbar spine as compared to the hypertensive patients not taking thiazide diuretics. PMID- 22774386 TI - Promoting heart health: an HBCU collaboration with the Living Heart Foundation and the National Football League Retired Players Association. AB - INTRODUCTION: Cardiovascular disease continues to be the leading cause of death in the United States and African Americans are disproportionately affected. Cardiovascular disease risk factors such as obesity, hypertension, family history of heart disease, and physical inactivity are often higher in African American young adults. The aim of the current study was to assess cardiovascular disease risk factors at a historically black college and university (HBCU) in North Carolina. METHODS: A collaborative partnership was established that included Living Heart Foundation, the NFL Retired Players Association and a HBCU. Ninety one students (77 females and 14 males) aged 18 to 55 years (mean, 24 y, SD = 9 y) were recruited via dissemination of flyers, brochures, mass e-mailing, and announcements. Demographic and medical history data were collected. Stata version 10.1 was used for all analyses. RESULTS: Fifty-three percent of the participants reported having experienced a chronic health condition, 32% were overweight (body mass index [BMI], 25-29.9 kg/m2) and 31% obese (BMI > or = 30 kg/m2). Five percent of females and 23% of males had high-density lipoprotein cholesterol of 40 mg/dL or less, indicative of a risk for developing heart disease. CONCLUSION: There is an urgent need to intervene among African American college students and address behavioral risk factors for cardiovascular disease. Such interventions may have a major impact on their overall and future health outcomes. Strategies to be employed need to focus on the integration of culturally appropriate healthy lifestyle programs into the curriculum and university health centers. Consultations with stakeholders for ideas and resources should be encouraged. PMID- 22774385 TI - Increasing knowledge of cardiovascular risk factors among African Americans by use of community health workers: the ABCD community intervention pilot project. AB - African Americans have higher rates of cardiovascular disease (CVD) and poorer outcomes compared to others. The American Diabetes Association and the National Diabetes Education Program have promoted use of the ABC approach (glycated hemoglobin A1c, blood pressure, cholesterol) for identifying and controlling the leading indicators of CVD risk. In the present study, researchers added a D factor, for depression, because this disorder is common and also predictive of CVD risk and of control of diabetes. Particularly among low-income African Americans, depression is frequently not targeted or treated. The current study tests the effectiveness of recruiting African Americans in churches and training community health workers (CHWs) to educate their peers about CVD and risk reduction. For the intervention group, CHWs participated in a 16-hour training session and delivered a 6-week tailored educational program with counseling sessions and demonstrations. The control group received a weekly lecture by clinical experts. The CHW active-learning intervention was more effective than lectures by clinical experts in increasing the knowledge of CVD risk. The only significant difference in clinical measures reflected a worsening of HbA1c levels in the control group; the CHW intervention group showed a slight improvement. Participants also learned self-management skills, such as taking blood pressure, measuring glucose, and reading labels. Nevertheless, more longitudinal research and a larger sample size are needed to confirm the impact of CHWs in community settings to change factors associated with CVD risk. PMID- 22774387 TI - The females against cancer educational series: a qualitative evaluation of mother/daughter knowledge and perceptions of human papillomavirus and its related cancers. AB - OBJECTIVE: To evaluate the knowledge, perceptions, and effectiveness of an human papillomavirus (HPV)/cervical cancer education/prevention program. METHODS: Approximately 50 middle and high school girls and their mothers participated in the 7-part educational series. Qualitative pre-evaluations and postevaluations were completed for every session, followed by culminating focus groups with mothers and daughters separately. RESULTS: Common themes included lack of basic knowledge about HPV and its related cancers. Additionally, mothers and daughters expressed difficulty in communicating with one another about healthy relationships; however, during the focus groups, both mothers and daughters discussed how they had utilized effective communication tools to discuss sensitive topics and make informed decisions together. CONCLUSIONS: Despite recent HPV prevention campaigns, more innovative strategies must be implemented to educate more mothers and daughters of HPV and its dangers. Additionally, in educating communities about HPV and associated cancers, more innovative strategies should be mobilized to trigger discussions regarding protective behaviors against HPV. PMID- 22774388 TI - Renal allograft capsular repair surgical technique to reduce allograft discard rates of kidneys with capsular injury. PMID- 22774390 TI - A case of malignancy in a thyroglossal duct cyst--recommendations for management. AB - Thyroglossal duct cyst carcinomas are rare tumors with just more than 200 cases published to date. This is a case report of a thyroglossal duct cyst harboring an occult carcinoma for which a Sistrunk operation was performed. Histopathological examination revealed a papillary carcinoma arising from a thyroglossal duct cyst after which the patient underwent a total thyroidectomy. With current evidence based guidelines lacking, we discussed some of the issues relevant to the surgical planning and postoperative management of such a patient. PMID- 22774389 TI - Staged laparoscopic ventral and incisional hernia repair when faced with enterotomy or suspicion of an enterotomy. AB - Enterotomy is a significant complication of laparoscopic ventral or incisional hernia repair (LVHR) and can be devastating if missed. Enterotomy occurs in 2.6% of patients undergoing LVHR and is missed 21.8% of the time. Controversy exists regarding the management of known or potential enterotomies. Approaches for managing recognized enterotomies during hernia repair are usually employed immediately; in a nonstaged fashion; and include laparoscopic enterotomy repair with immediate LVHR, laparotomy for repair of enterotomy with concomitant LVHR, or conversion to laparotomy for both enterotomy and hernia repair. The staged approach for managing recognized or potential enterotomies is less commonly employed and involves laparoscopic repair of enterotomy, admission, and delayed but definitive laparoscopic hernia repair in the same hospitalization. The presence of known or potential enterotomies during LVHR presents a difficult problem and may be a contraindication for immediate placement of prosthetic because of increased risks posed for abdominal infection, reoperation, prosthetic removal, hernia recurrence, and death. The staged approach--with a 2- to 5-day delay--represents a safe solution to this challenging problem. We present 4 cases managed via staged approach due to an enterotomy, risk factors, and suspicion for missed or delayed enterotomies augmented by a review of the literature. PMID- 22774391 TI - The optimal management of patients with systemic scleroderma and coronary artery disease. PMID- 22774392 TI - Just saying no to NOTA: court permits the sale of hematopoietic stem cells. PMID- 22774393 TI - The forgotten MASH surgeon: the story of Alvin Vincent Blount Jr, MD. PMID- 22774394 TI - Verina Morton Jones, MD. AB - The purpose of this historical article is to demonstrate, as the biography of Verina Morton Jones, MD, is uncovered, the difficulties inherent in researching original source material on the lives of 19th- and early 20th-century African American physicians as well as the great benefits derived from doing this research. The procedures used include basic archival research and close examination of published materials about her in the past, in conjunction with oral history. Original correspondence from Dr Morton Jones to her niece and nephew is used to illustrate events in her life and the thoughts and attitudes she expressed. Some of these thoughts and attitudes reflect those current situations in which African Americans found themselves, and others are quite unique, no doubt owing to her privileged position in the African American community. The principle conclusions reached include the great benefits derived from doing this kind of research, as difficult and time-consuming as that may be, with the enhanced knowledge and appreciation of the heritage of African American physicians, and insights into American social history during this period. PMID- 22774396 TI - The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. AB - BACKGROUND: PCOS is the main cause of infertility due to metabolic, hormonal and ovarian dysfunctions. Women affected by PCOS often suffer of insulin resistance and of a compensatory hyperinsulinemia. These conditions put the patients at risk of developing several metabolic disorders. Both myo-inositol (MI) and D-chiro inositol (DCI) glycans administration has been reported to exert beneficial effects at metabolic, hormonal and ovarian level. Beside these common features, MI and DCI are indeed different molecules: they belong to two different signal cascades and regulate different biological processes. AIM: In this study, we aim to verify whether the two molecules have a synergistic action by acting on their specific cellular pathways. The effectiveness in reducing the risk of metabolic syndrome as well as in enhancing the ovarian functions of a combined therapy with MI and DCI was compared to a mono therapy in a randomized controlled trial. METHODS: Fifty overweight women with PCOS were enrolled and divided in two groups to receive MI and DCL (MI+DCI group) or MI alone (MI group) for a period of six months. Baseline measurements were repeated at three months (T1) and at the end of the treatment (T2). RESULTS: At the end of the treatment, both MI and MI+DCI groups showed an improvement of the metabolic parameters and no significant differences were found. As expected, the combined supplementation with MI and DCI resulted to be more effective, compared to the MI group, after three months of treatment. CONCLUSIONS: The combined administration of MI and DCI in physiological plasma ratio (40:1) should be considered as the first line approach in PCOS overweight patients, being able to reduce the metabolic and clinical alteration of PCOS and, therefore, reduce the risk of metabolic syndrome. PMID- 22774395 TI - Comparison of the potency of 10 different brands of Serenoa repens extracts. AB - BACKGROUND: The extract of Serenoa repens is the phytopharmaceutical product most often used for the treatment of urological symptoms associated with benign prostatic hyperplasia (BPH). Several extracts are commercially available but extraction processes vary between manufacturers and thus not all these products are equivalent in terms of active ingredient content and composition of preparations. AIM: As there is a paucity of comparative studies, we compared the activity of different extracts of Serenoa repens widely available on the world market. MATERIALS AND METHODS: Beltrax Uno, Permicaps, Permixon, Prostadyn, Prostagutt, Prostamen, Prostamol Uno, ProstaX, Urocaps and Urogutt were assayed for 5-alpha-reductase activity on 10 day fibroblasts and epithelial cells cocultures. Human fibroblast growth factor (hFGF)-induced-proliferation inhibition was also assayed. RESULTS: As to extract activity, differences were observed between the tested extracts, but all were able to inhibit 5-a-reductase types I and II isoenzymes (5alphaR-I and 5alphaR-II) as well as fibroblast proliferation. CONCLUSIONS: Extract potency differs between products and so does proliferation inhibition potency. Quantitative and qualitative variations in the active ingredient are likely to account for these differences. PMID- 22774397 TI - Effects of melatonin on testis histology, oxidative stress and spermatogenesis after experimental testis ischemia-reperfusion in rats. AB - BACKGROUND: Testicular torsion due to oxidative stress results in infertility and testicular damage which can be preventable an important health problem worldwide. AIM: The purpose of the present study was to investigate the changes of malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS) levels; histopathological alterations; morphology, concentration and motilities of the sperm in post ischemic reperfused (I/R) testis tissue. MATERIALS AND METHODS: Forty adult male Wistar rats were carried out and were randomized to five groups; (1) Control group, (2) Ipsilateral left testis ischemia, (3) Melatonin plus ipsilateral left testis ischemia, (4) Contralateral right testis ischemia, 5. Melatonin plus contralateral right testis ischemia. After 1 h ischemia and 24 h perfusion; MDA, TAS and TOS levels were measured, histopathological alterations were determined using by Johnsen's score (JS) and sperm morphology, concentration, motility were examined. RESULTS: MDA, TAS and TOS levels of the testis tissue did not change in all groups (p > 0.05 for all). JS was decreased in I/R group and melatonin treatment reversed histopathological changes and increased JS both in ipsilateral and contralateral testis. Abnormal sperm rate significantly increased in I/R group and melatonin administration changed abnormal sperm rate to normal. CONCLUSIONS: As a result, the present study demonstrated that testicular damage occurs following I/R without an increase of MDA, TAS and TOS levels. Our results also suggested that melatonin is a potent antioxidant agent in preventing testicular I/R injury, as shown by increased JS and changed abnormal sperm rate. PMID- 22774398 TI - Modulation of the platelet serotonin transporter by thermal balneotherapy: a study in healthy subjects. AB - BACKGROUND: Although the beneficial effects of balneotherapy have been recognized since a long time, a few information is available on the biological mechanisms underlying them and the subjective feelings of increased well-being and mood. AIM: The links between the serotonin (5-HT) system and mood prompted us to investigate the 5-HT platelet transporter (SERT), which is considered a reliable, peripheral marker of the same structure present in presynaptic neurons, in 30 healthy volunteers before (t0) and 30 minutes after (t1) thermal balneotherapy with ozonized water, as compared with a similar group who underwent a bath in non mineral water. MATERIALS AN METHODS: The SERT was evaluated by means of the specific binding of 3H-paroxetine (3H-Par) to platelet membranes. Equilibrium saturation binding data, the maximal binding capacity (Bmax) and the dissociation constant (Kd), were obtained by means of the Scatchard analysis. RESULTS: The results showed that, while Bmax values did not change in both groups, the Kd values decreased significantly at t1 only in those subjects who bathed in ozonized water. CONCLUSIONS: The results of this study, while showing a decrease of the dissociation constant (Kd) which is the inverse of affinity constant, of 3H-Par binding to SERT in all subjects after balneotherapy and not in those bathing in normal water, suggest that SERT modifications may be related to a specific effect of ozonized water and, perhaps, also to the increased sense of well-being. PMID- 22774399 TI - The effect of day and night shifts on oxidative stress and anxiety symptoms of the nurses. AB - BACKGROUND: Oxidative stress is believed to have a role in the development of chronic diseases. It is also known that long-term night and shift work in nurses might be associated with many health-related problems like fatigue, sleep problems, anxiety and difficulties in maintaining regular lifestyles. AIM: In this study, we aimed to evaluate the changes of oxidative stress parameters and anxiety indexes of the nurses on day and night shifts. MATERIALS AND METHODS: One hundred and twenty nurses in ordinary service and intensive care unit (ICU) were enrolled to the study. Subjects were divided into 2 groups; group 1 (n = 60) consisted of nurses working in a day shift and group 2 (n = 60) as working in the night shift. Further, both groups were divided in to 2 groups again; group la and 2a (both n = 30) who working in the ICU, group 1b and 2b (both n = 30) in the ordinary service. Just before and the end of the shifts, blood samples were obtained to measure total antioxidant status (TAS) and total oxidant status (TOS). Oxidative stress index (OSI) was calculated. Anxiety index were determined at the end of the shift using State-Trait Anxiety Inventory index. RESULTS: Oxidative stress parameters were increased in all nurses at the end of the day and night shifts (p < 0.05). However, both in service and ICU nurses TAS, TOS, and OSI levels were not significantly different at the beginning and the end of the shifts (p > 0.05). Anxiety indexes of each ordinary service and ICU nurses were found to be similar (p > 0.05). CONCLUSIONS: Ordinary service and ICU nurses' oxidative stress parameters and anxiety indexes were not different and all nurses suffer the similar effects of the shifts both in day and night. PMID- 22774400 TI - Renoprotective activity of telmisartan versus pioglitazone on ischemia/reperfusion induced renal damage in diabetic rats. AB - OBJECTIVES: Diabetes mellitus (DM) causes organ dysfunction and increases the sensitivity of organs to damages.To test this hypothesis, we used renal ischemia/reperfusion (I/R) experiment to evaluate the renoprotective activity of telmisartan versus pioglitazone on I/R induced renal damage in diabetic rats. MATERIALS AND METHODS: Renal I/R was performed in both normal and diabetic rats. The protocol comprised ischemia for 45 minutes followed by the reperfusion for 24 hours and a treatment period of two weeks before induction of ischemia. RESULTS: Renal I/R in both control and diabetic rats induced marked renal dysfunction associated with a significant increase in the arterial pressure, tumor necrosis factor alpha (TNF-alpha) levels, and the malondialdehyde formation (MDA). The activities of the anti-oxidant enzymes such as reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were found to be decreased significantly compared to control rats. Diabetic animals that underwent renal I/R exhibited a significant increase in all the studied parameters with a reduction in the anti-oxidant enzymes as compared to non-diabetic rats. Histo-pathological studies confirm these results. Treatment with pioglitazone or telmisartan demonstrated a significant improvement in the reperfusion-induced renal injury in comparison with diabetic I/R group, without difference between the two treated groups. Therefore, the treatment with pioglitazone or telmisartan have the same corrective effect. CONCLUSIONS: Type 2 diabetes had exaggerated renal I/R injury in STZ-NAD induced diabetes. Telmisartan treatment is equieffective as pioglitazone in attenuating acute I/R-induced renal injury in diabetic rats by a modification in the oxidative stress and the inflammation. PMID- 22774401 TI - Interaction of -55CT polymorphism of UCP3 gene with Trp64Arg polymorphism of beta3adrenoreceptor gene on insulin resistance in obese patients. AB - BACKGROUND: The aim of our study was to investigate the interaction of tryptophan to-arginine (Trp64Arg) missense mutation in the beta3 adrenoreceptor (Beta3AR) with polymorphism in the UCP3 promotor (-55C->T) on insulin resistance in obese patients. DESIGN: A population of 212 obese patients was analyzed. A bipolar electrical bioimpedance, a biochemical analysis and concentrations of adipocytokines were assessed. RESULTS: One hundred and sixty-two patients (76.4%) had the genotype Trp64/Trp64 (wild type group) and 50 patients Trp64/Arg64 (23.6%) (mutant type group). One hundred and seventy five (87.2%) had the genotype -55CC (wild type group) and 27 patients (22.8%) -55CT (mutant type group). Five patients (2.4%) had both polymorphisms Trp64/Arg64 and -55CT. Patients with one or both mutant genotypes had higher BMI, weight, fat mass, systolic blood pressure and waist circumference than wild type patients. Patients with 55CT or 55CT and Trp64Arg genotype had higher BMI, weight, fat mass, waist circumference, waist to hip ratio glucose, insulin, triglycerides and HOMA than wild type or Trp64Arg mutation. CONCLUSION: Higher concentrations of insulin, HOMA, triglycerides, glucose, BMI, weight, fat mass, waist to hip ratio and waist circumference were observed in patients with -55CT genotype alone or -55CT plus Trp64Arg genotypes than in patients without mutation or only Trp64Arg mutation. PMID- 22774402 TI - Effect of hypoglycemic drugs on aspirin resistance in patients with diabetes mellitus. AB - BACKGROUND: Aspirin reduces the odds of an arterial thrombotic event in high-risk patients. However, 10%-20% of patients with an arterial thrombotic event who are treated with aspirin have a recurrent arterial thrombotic event during long-term followup. Aspirin resistance has been described in some patient populations such as those with an acute coronary syndrome, ischemic stroke, percutaneous coronary intervention with drug-eluting stent, stent re-stenosis, and diabetes mellitus (DM). The aim of this study was to assess aspirin resistance and to compare it to the use of oral anti-diabetic drugs and insulin in patients with diabetes. METHODS AND RESULTS: Platelet aggregation was measured after aspirin treatment in 101 diabetic patients undergoing percutaneous coronary intervention. Two patient populations were included in the investigation: use of insulin (group 1) and use of oral anti-diabetic agents (OAD) (group 2) in diabetic patients. Platelet aggregation was determined using a multichannel Multiplate analyzer. Among group 1 patients, 4.7% were aspirin non-responders and among group 2 patients, 8.6% were aspirin non-responders. Statistical differences were not found between the groups (p = 0.359). CONCLUSIONS: This study demonstrated that there was no significant difference in aspirin resistance between type 2 diabetes mellitus patients on insulin treatment and type 2 diabetes mellitus patients on OAD treatment. PMID- 22774403 TI - The role of 99mTc-MIBI scintigraphy in the management of patients with pulmonary tuberculosis. AB - BACKGROUND: This study aimed to determine whether 99mTc-methoxyisobutylisonitrile (MIBI) scanning could improve diagnostic accuracy of pulmonary tuberculosis (PTB) and help clinical decision making for an accurate management. MATERIAL AND METHODS: 99mTc-MIBI scintigraphy was performed in 62 cases of PTB 34 cases had active pulmonary tuberculosis (APTB) and were at the beginning of antituberculosis medication (group 1) as well as 28 cases had inactive pulmonary tuberculosis (IPTB) and were post antituberculosis medication (group 2). The qualitative and semiquantitative findings of both scanning methods were assessed. For semiquantitative evaluation, regions of interest (ROIs) were drawn over the lesion (L), non-lesion (NL) and neck soft tissue (NST). The mean count values of ROIs were obtained and L/NL and L/NST were calculated. RESULTS: Thirty-four patients with APTB (15 males and 19 females; mean age of 47.85 +/- 1.91 yrs) and 28 cases with IPTB (9 male and 19 females; mean age of 53.96 +/- 2.33 yrs) were included in this study. The sensitivity, specificity, accuracy, positive and negative predictive (PPV and NPV) values of 99mTc-MIBI were 88.2%, 75%, 82.2%, 81.1% and 84% respectively. The mean value of L/NL in the APTB for 99mTc-MIBI was 1.45 +/- 0.18 and L/NST was 1.57 +/- 0.26 which was significant statistically (p < 0.00). CONCLUSIONS: The study demonstrated that 99mTc-MIBI scanning can be complementary to other diagnostic techniques especially in patients with indeterminate APTB and those in whom recurrent disease is suspected. In addition, because of its availability, rather low costs, easy performance, and objective semiquantitative information supplied, 99mTc-MIBI scanning might be establish in routine imaging center to assess the pulmonary tuberculosis. However, further exploration is needed to validate its clinical role. PMID- 22774404 TI - Interleukin-8 induces the endothelial cell migration through the Rac 1/RhoA p38MAPK pathway. AB - BACKGROUND AND OBJECTIVES: Endothelial cell migration is essential for tumor angiogenesis, and interleukin-8 (IL-8) has been shown to play an important role in tumor growth, angiogenesis, and metastasis. The objective of this study was to investigate the molecular mechanism of IL-8 induced endothelial cell migration in vitro. MATERIAL AND METHODS: Fluorescence microscope was used to study the distribution of cytoskeleton. The expression of Rac1 and RhoA protein was detected by western blotting. After endothelial cells were transfected by lipofectamine 2000 reagent, the Transwell chamber motility assay was applied to observe the migration of endothelial cells induced by IL-8. The active p38MAPK (mitogen-activated protein kinase) was evaluated by the p38MAPK activation assay. RESULTS: We demonstrated that IL-8 activated cell migration can be impaired by p38MAPK inhibitor, suggesting the participation of p38MAPK in the cell migration. Our results indicated that p38MAPK signaling is required for membrane ruffles, lamellipodia extensions, and actin stress fibers formation induced by IL-8. Furthermore, p38MAPK inhibitor led to increased Rac1 and RhoA expression in IL-8 treated EA.hy926 cells. In addition, IL-8 induced p38MAPK activation was suppressed by dominant-negative mutant for Rac1 and RhoA. CONCLUSIONS: Our study demonstrates that IL-8-Rac1/RhoA-p38MAPK signaling pathway plays a vital role in the IL-8-induced endothelial cell migration, and it provides new insight into the molecular mechanisms by which IL-8 contributes to tumor angiogenesis and metastasis. PMID- 22774405 TI - Can we decrease the acute proctitis in prostate cancer patients using hyaluronic acid during radiation therapy: a prospective historically controlled clinical study. AB - BACKGROUND: The purpose of this study was to evaluate the ability of rectal suppository of hyaluronic acid to limit symptoms of acute radiation proctitis in patients with prostate cancer (PC). MATERIALS AND METHODS: From January 2011 to October 2011, 50 consecutive patients, undergoing radiotherapy with radical or adjuvant intent for PC, were invited to use rectal suppository of hyaluronic acid (HA: Cicatridina suppository, Farma-Derma s.r.l., Sala Bolognese, BO, Italy) daily, before radiation delivering. An historical group was used as an external control. Acute rectal toxicity was scored weekly according to RTOG criteria. Time to occurrence of acute rectal toxicity was taken as endpoint. RESULTS: Compliance was good. Only 2% of HA treated patients had a G2 acute proctitis versus 7% of historical group, globally a difference was observed in rate of acute proctitis between the experimental arm and the control group: 32% in experimental arm versus 45% in control group (p = 0.08). A delay in the onset of acute rectal toxicity in patients treated with HA (p = 0.04) was showed. CONCLUSIONS: Our findings suggested the role of HA in reducing acute proctitis in prostate cancer patients treated with radiotherapy. Further trials are needed to confirm these results. PMID- 22774406 TI - A novel approach to study oxidative stress in thyroid diseases: a preliminary study. AB - BACKGROUND AND OBJECTIVES: Recently, several Authors have emphasized the relationship between oxidative stress and thyroid tumors. Several methods have been proposed in the literature for the measurement of oxidative stress in human tissues, although the high reactivity and short half life of reactive oxygen and nitrogen species make difficult their direct determination. Here we propose a novel approach for the determination of oxidative stress in human tissues, taking into account the relationship between free radicals and thyroid diseases. MATERIALS AND METHODS: Our goal in this preliminary study, was to demonstrate the opportunity to use the coupling of the EPR-spin trapping technique with the hydroxylamine 1-hydroxy-3-carboxy-pyrrolidine, to detect oxidative stress in the human blood of patients with thyroid disease. RESULTS: Our preliminary findings confirm that this is a sensible, precise and valid method to study the oxidative stress and encourage us to continue the project. CONCLUSIONS: Our next goal will be to enroll patients affected by different thyroid diseases and to study the effect of some antioxidants in the management of the disease. This will allow to better understand the pathological path that binds the formation of reactive oxidizing species to the thyroid cancer and eventually to take into account the antioxidant therapy, as a possible additional "therapeutic weapon". PMID- 22774407 TI - Reduction of the morning blood pressure surge treated with olmesartan in Chinese patients with mild to moderate essential hypertension--a multicenter, open-label, single treatment group clinical study. AB - OBJECTIVE: To investigate the morning blood pressure surge (MBPS) in Chinese patients with mild to moderate essential hypertension treated with long-term administration of olmesartan, an angiotensin II receptor antagonist according to ambulatory blood pressure monitoring (ABPM). MATERIALS AND METHODS: In a multi center, prospective study, we investigated the long-term efficacy of olmesartan by ABPM in 18-75 years-old Chinese patients with mild to moderate hypertension (clinic diastolic blood pressure [DBP] 90-109 mm Hg and systolic blood pressure [SBP] < 180 mmHg). After a 1 week placebo runin, 87 patients were treated with olmesartan 20 mg once daily in the morning for 24 weeks. Ambulatory blood pressure monitoring was conducted at baseline and at the end of 24 weeks. At baseline, patients with an MBPS > or = 23 mmHg were classified as the MBPS group (n = 41), and all other patients were classified as the non-MBPS group (n = 46). RESULTS: The mean systolic and diastolic blood pressures (SBP/DBP) over 24 hours were reduced from 141.78 +/- 12.8/91.17 +/- 7.34 to 128.35 +/- 15.86/83.58 +/- 9.53 mmHg (p < 0.01). The mean blood pressure in the final 6 hours of the dosing interval dropped from 135.75 +/- 5.84/87.29 +/- 4.80 mmHg to 122.98 +/- 6.46/80.49 +/- 4.31 mmHg (p < 0.01). The MBPS for SBP/ DBP were reduced from 35.68 +/- 8.85/29.77 +/- 17.19 mmHg to 28.62 +/- 15.08/19.08 +/- 11.01 mmHg in the MBPS group (p < 0.05). The reductions in MBPS after treament with olmesartan were significantly different between the two groups (p < 0.01). CONCLUSIONS: Olmesartan effectively reduces blood pressure in patients with essential hypertension, and olmesartan especially reduces the MBPS in MBPS-prone patients. PMID- 22774408 TI - Assesment of correlation between bispectral index and four common sedation scales used in mechanically ventilated patients in ICU. AB - PURPOSE: The aim of this study was to compare the correlation between bispectral index (BIS) monitor and four commonly used subjective clinical scales (Ramsay Sedation Scale (RSS), Richmond Agitation Sedation Scale (RASS), Sedation Agitation Scale, Adaptation to Intensive Care Environment scale) in mechanically ventilated patients in intensive care unit (ICU). In addition, comparison of responsiveness of the clinical scales in respect to BIS changes is another goal of this study. MATERIALS AND METHODS: Mechanically ventilated thirty patients who required sedation for any reason were enrolled to study. Patients who needed neuromuscular blockade, patients with known hearing and visual problems, neurological diseases, anoxic encephalopathy, mental retardation and who developed hemodynamic instability (mean arterial pressure below 60 mmHg) and hypoxemia (sPO2 below 90%) during follow-up were excluded. Starting before the initiation of sedation, first BIS scores then clinical sedation scales were evaluated. This procedure is repeated every 2 hours for 24 hours. RESULTS: All of the four clinical scales were significantly correlated with BIS. BIS and clinical scale values, except Adaptation to Intensive Care Environment scale, showed significant changes compared to baseline after the initiation of sedation. Ramsay and Richmond scales showed the highest correlation with BIS (respectively, r = 0.758, r = 0.750). Adaptation to Intensive Care Environment revealed the lowest correlation (r = 0.565). CONCLUSIONS: All of the scales were significantly correlated with BIS. RSS and RASS showed higher correlation than other scales. As a conclusion: RSS and RASS can be used for monitoring the depth of sedation in mechanically ventilated patients in ICU. PMID- 22774409 TI - A review on an update of NS5B polymerase hepatitis C virus inhibitors. AB - BACKGROUND: Hepatitis C virus (HCV) infection is widespread, abhorrently under diagnosed, and radically under-treated. Globally, infection with HCV is a major cause of acute hepatitis and chronic liver disease. Therefore, novel HCV inhibitors are required for the treatment of the HCV infected patients. OBJECTIVE AND PERSPECTIVES: This review gives the detailed knowledge of upcoming therapy such as NS5B polymerase inhibitors that are urgently needed. CONCLUSION: In the past decade, intensive hard work has focused on the discovery of both structural and nonstructural inhibitors of the HCV NS5B polymerase. These demanding efforts have resulted in various promising agents advancing in clinical development with emphasis on clinical efficacy and impact for future combination studies. PMID- 22774410 TI - Assessment of immunochemotherapy and stem cell transplantation on EBV-associated hemophagocytic lymphohistiocytosis in children: a systematic review and meta analysis. AB - BACKGROUND AND OBJECTIVES: Although immunochemotherapy had been reported to be effective initial treatment for patients with Epstein Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH), and stem cell transplantation (SCT) was employed for patients with refractory disease, the long-term outcome of these patients underwent such treatment remained uncertain. The main purpose of this study was to make a primary system review on the outcome of EBV-HLH patients treated with immunochemotherapy and/or SCT. MATERIAL AND METHODS: A system review and meta analysis was conducted on studies which collected from published PubMed and China Knowledge Resource Integrated Database (CNKI). The analysis was based on clinical characteristics and follow-up. Search strategy and selection criteria were identified by relevant articles, the period was defined from January 1990 to October 2010. Search terms included all relevant terms. English and Chinese language papers were reviewed. RESULTS: A total of 11 articles include 342 EBV HLH patients that were identified with our search terms fulfilled the eligibility criteria. Overall 104/342 patients (30.4%) died at the end of respective study. In 288 patients who did not receive SCT, 93/288 patients (32.3%) patients died. While in 54 patients who underwent SCT, 11/54 patients (20.4%) died at the end of respective study. Four articles had the contents both of immunochemotherapy and SCT. When using a meta analysis compared the mortality between immunochemotherapy and SCT groups, there was no statistical significance could be found, the Odds Ratio is 1.10 (0.43-2.84), (p = 0.84). When compared the mortality between SCT group and total EBV-HLH patients, there was still no statistical significance could be found, the Odds Ratio is 0.99 (0.39-2.53), (p = 0.98). CONCLUSION: Etoposide-containing immunochemotherapy and SCT both decreased the mortality in EBV-HLH patients in the past decade. There was not enough evidence to suggest that SCT is better than immunochemotherapy in children with EBV-HLH. And such result may justify further research. PMID- 22774411 TI - Effects of mesenchymal stem cells in critical size bone defect. AB - BACKGROUND AND OBJECTIVES: The aim of this study was to compare culture-expanded, bone marrow-derived mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) loaded to biphasic calcium phosphate (BCP) bone ceramic in the repair of rat calvarial bone. MATERIALS AND METHODS: Critical-size (7 mm dia.) calvarial defects were prepared in the frontal-parietal bones of 90 adult female Sprague Dawley rats. Rats were randomly divided into 5 groups, according to defect filling, as follows: Group I (n = 21), BCP; Group II (n = 21), BCP+PRP; Group III (n = 21), BCP+MSC; Group IV (n = 21), BCP+PRP+MSC; Group V (n = 6) (control), no treatment. Animals were sacrificed at 2, 8 and 12 weeks postsurgery and bone regeneration was evaluated both histologically and immunohistochemically. RESULTS: Statistically significant differences were observed in bone osteoblastic activity in calvarial defects among the groups (p < 0.05). PRP and MSC used in combination with BCP as a defect filling resulted in greater osteoblastic bone formation activity when compared to the use of BCP alone. CONCLUSIONS: The combination of mesenchymal stem cells, platelet rich plasma and synthetic bone substitute was found to be more effective in inducing new bone formation (osteogenesis) than the use of platelet rich plasma combined with synthetic bone substitute and the use of synthetic bone substitute alone. PMID- 22774413 TI - A mass in the posterior mediastinum; extramedullary haemopoietic tissue. AB - Extramedullary haematopoiesis is a very rare cause of a posterior mediastinal tumour and may be clinically confused with many other mediastinal tumours; benign or malignant. Extramedullary haematopoiesis is a really rare cause of haemothorax and usually it is diagnosed incidentally. Extramedullary masses complicating thalassemias, apart from the known complications, may also bleed and produce acute manifestations like dyspnoea and fatigue. Pathologically, the masses are soft, deep red, and resemble spleen tissue on the cut surface. Histologically, they are formed of hematopoietic tissue mixed with adipose elements. The mass is extremely vascular and contains some fibrous tissue. This particular structure renders the mass prone to haemorrhage. We report a case of posterior mediastinal extramedullary haematopoietic mass in a 56-year-old man who presented with non specific symptomatology and a paravertebral mass on chest X-ray and in the chest computed tomography. A percutaneous biopsy approach could be technically difficult due to the special location of the mass. Video assisted thoracic surgery (VATS), is a minimal invasive and alternative way of diagnosis, biopsy and treatment of these cases. Diagnosis was achieved in our patient by mini thoracotomy and open biopsy in order to prevent bleeding or neurological damage. PMID- 22774412 TI - Laparoscopic vs. open appendicectomies: results obtained by junior surgeons at a British University Hospital. AB - BACKGROUND: The laparoscopic approach for appendicectomies remains a frequent topic of debate. In this study we report the experience with laparoscopic (LA) and open appendicectomies (OA) achieved in a British University Hospital over one year where most of these operations have been conducted by junior trainees. METHODS: Retrospective review of LA and OA performed at the Whipps Cross University Hospital of London (U.K.). Outcomes measured were the operating time, length of hospital stay and post-operative complications. RESULTS: Between January and December 2008 205 appendicectomies have been performed on adult patients. Eighty-eight per cent of the procedures were conducted by junior surgeons. The operating time was significantly shorter for the OA vs. LA patients (55 +/- 26.8 vs. 83 +/- 26.9 min, p < 0.01). The hospital stay confirmed a significant advantage for LA (2.2 vs. 3.7 days, p = 0.02). No significant differences were present among techniques for the overall morbidity, post operative intra-abdominal abscesses and rate of readmissions. CONCLUSIONS: Under adequate supervision LA can be safely performed by junior surgeons and reduces the hospital stay. PMID- 22774414 TI - A 9-year follow-up of a girl with pyridoxine (vitamin B6)-dependent seizures: magnetic resonance spectroscopy findings. AB - Being an extremely rare condition makes the diagnosis of pyridoxine-dependent seizures (PDS) difficult. Early diagnosis of PDS is very important to prevent unwanted clinical outcomes. Elevated levels of glutamate and decreased levels of y-aminobutyric acid (GABA) in the frontal and parietal cortices are detected in this disorder. Here we present an 18 year old girl with PDS, who was reported 9 years ago with Magnetic Resonance Spectroscopy (MRS) findings. Present and past MRS findings showed a decrease in N-acetyl-aspartate-to creatine ratio on MRS. In this case it is surprising that neuronal damage has been preceded despite the administration of accurate treatment. That can be because of delay in treatment and/or under treatment. PMID- 22774415 TI - A congenital tympanic membrane cholesteatoma (CTMC) in the adult: a case report. AB - OBJECTIVE: We present an additional very rare case of a congenital tympanic membrane cholesteatoma (CTMC) in the adult. METHOD: Case report and literature review of CTMC. CASE REPORT: A 54-year old man was referred to us by his primary care physician who noted a white mass on the right tympanic membrane without prior history of otorrhea, tympanic perforations or previous otologic procedures. The pearl was about 5 mm diameter, centered on the umbo of a normal tympanic membrane (TM). The audiogram and the tympanogram was absolutely normal. CT confirmed a soft round shape tissue mass, located in the centre of the TM near umbo. The mass protruded both in the auditory canal and in the middle ear space, touching the malleus extremity, without any relationship with medial wall of the cavum tympani. A surgical excision was performed using a "minimal" retroauricolar transcanalar approach: the CTMC was located into the thickness of the TM, between epidermic and mucous layers. The ossicular chain was preserved intact. A partial myringoplasty (underlay technique) using a temporalis fascia graft was necessary. Histopathology confirmed a cystic cholesteatoma. After two months and one year follow-up, otoendoscopy showed a well-healed TM with a preserved normal audiogram and tympanogram. DISCUSSION: This exceptional (probably the first reported) case showed the possible localization of the CC in the TM, also in the adult. Criteria for classification of a TM cholesteatoma as congenital and possible pathogenetic mechanisms are discussed. PMID- 22774416 TI - An unusual bilateral fibroepithelial pharyngeal polyps: report of a case. AB - Fibroepithelial polyps are benign polypoid lesions arising from the mesodermal tissue and composed of varying amounts of stroma covered by squamous epithelium. We report the unusual case of a 57 years old man who visited our Hospital with complains of airway obstruction and uneasy feeling like a foreign body deep in his throat. After medical examination we find a large mass on the right side of his hypopharinx and we resected tumour as an emergency procedure. Postoperative recovery was good. After two years patient came again in our Hospital with the same feeling and we found another lesion on the left side of his hypopharynx. We repeated the same surgical procedure like the first time. In medical review that is a rare lesion with small number of references. In this case, fibroepithelial polyps arose from the hypopharynx and these potentially fatal lesions may have resulted in complete airway obstruction. PMID- 22774417 TI - Hematemesis from esophageal varices associated with esophageal perforation: sclerotherapy and endoscopic clipping. AB - A 46-year-old man was referred to our Unit for hematemesis. The medical history of the patient revealed an HCV-related cirrhosis, a human immunodeficiency virus (HIV) infection and recent and persistent episodes of emesis. An urgent gastroscopy disclosed evidence of active bleeding from varices of the lower third of the esophagus and a concomitant laceration of the esophageal wall due to the emesis. These two conditions have been endoscopically diagnosed and successfully treated by sclerotherapy and endoscopic clipping. PMID- 22774418 TI - Non-invasive blood pressure cuff induced lower extremity wound in a diabetic patient. PMID- 22774420 TI - Working memory capacity and individual differences in the making of reinstatement and elaborative inferences. AB - This study investigated the role of working memory capacity on the making of reinstatement and causal elaborative inferences during the reading of natural texts. In order to determine participants' working memory capacity, they were asked to take the reading span task before they took part in the study. Those participants that were identified as high or low working memory capacity readers were asked to perform a lexical decision task in two conditions: pre-inference and inference. In the pre-inference condition, target words representing reinstatement or causal elaborative inferences were presented immediately before the sentences that were predicted to prompt them. In the inference condition, the target words were presented immediately after the sentences that were predicted to prompt the inferences. Results indicated that, for the high working memory capacity readers, lexical decision times were faster at the inference compared to the pre-inference locations for both types of inferences. In the case of low working capacity readers, lexical decision times were faster at the inference compared to the pre-inference locations only for reinstatement inferences. These findings suggest that working memory capacity plays a role in the making of causal inferences during the comprehension of natural texts. PMID- 22774419 TI - Basic color terms use by aged observers: lens aging and perceptual compensation. AB - Basic Color Terms (BCTs) use by aged people (normal and tritanomalous) was analysed on the basis of the results provided by two visual search tasks. One task (mapping) required participants to select every stimulus that could be included in a specific BCT. Another task (best representative) required participants to select the stimulus that most accurately identified a BCT. Both tasks' results were used for two different goals. First (descriptive level), to specify the main differences between aged and young people in their use of BCTs (dimensions provided by multidimensional scaling, confusions between specific pairs of BCTs). Second (explicative level), to compare the accuracy of three models for predicting aged people's performance. Model A (filtering without compensation) assumed that aged people must use BCTs as young people do when responding to stimuli similar to the ones produced by lens aging. On the contrary, model B (filtering with compensation) assumed that lens aging effects were partially compensated by a von Kries-type mechanism (white normalisation). Finally, model C (tritan lines) assumed that ocular aging only influences S cone responses (tritan responses). Results showed that model B was the most accurate with the percentage of explained variance over 90% for both aged groups. PMID- 22774421 TI - The effect of age on decision making according to the Iowa gambling task. AB - Aging has been associated with several brain changes that often affect the cognitive functioning of adults, but changes in executive functions, particularly in the field of decision making, have not been fully investigated. The Iowa Gambling Task (IGT) is a widely used tool to evaluate decision making, but little is known about the effect of age on its results. This study used the IGT and compared healthy young (n = 40) and elderly (n = 40) adults to evaluate their decision making processes. There were significant differences in the learning curve of the two age groups, but no difference in overall IGT performance. The results for the first IGT block were different from those of the rest of the task, and the group of elderly adults had a better performance in this block. Elderly adults also showed a preference for deck A, the one that resulted in greater losses. Findings confirmed the results of other studies, which reported that the IGT block score is the variable with the greatest sensitivity to age in this instrument. PMID- 22774422 TI - Acoustic markers associated with impairment in language processing in Alzheimer's Disease. AB - This study broaches in a novel way the analysis of cognitive impairment characteristic of the early stages of Alzheimer's Disease (AD). Specifically, we attempt to determine the acoustic speech parameters that are sensitive to the onset of the disease, and their association with the language deficit characteristic of AD. Speech analysis was carried out on 21 elderly patients with AD using Praat software, which analyzes the acoustic components of speech. The data obtained were subjected to stepwise regression, using the overall scores obtained in the test as the criterion variable, and the scores on the frequency, amplitude and periodicity variables as predictors of performance. We found that the percentage of voiceless segments explains a significant portion of the variance in the overall scores obtained in the neuropsychological test. This component seems to be related mainly to the patient's ability in phonological fluency. This finding could permit the creation of a diagnostic test for AD through analysis of the acoustic speech parameters at very low cost in terms of both time and resources. PMID- 22774424 TI - The effects of base frequency and affix productivity in Spanish. AB - In this study we present the results of a lexical decision experiment where the variables manipulated are Base frequency and Affix productivity. The results show significant main effects for both variables for the first time in Spanish, as well as for the interaction between the two. However, pair analysis shows that the Base Frequency effect is not significant when the Affix Productivity is low, while the Affix Productivity effect is produced regardless of the Base Frequency. The results for the main effects show a morphological representation in the lexicon, whilst the results of pair comparisons suggest a different representation of stems and affixes in the lexicon. These results support the idea that complex words incorporating unproductive affixes are processed differently from words incorporating productive affixes. The results are finally explained in terms of a hierarchical model of morphological processing. PMID- 22774423 TI - Differential diagnosis between apraxia and dysarthria based on acoustic analysis. AB - Acoustic analysis provides objective quantitative measures of speech that enable a comprehensive and accurate understanding of motor disorders and complement the traditional measures. This paper aims to distinguish between normal and pathological speech, more specifically between apraxia of speech and spastic dysarthria in native Spanish speaking patients using acoustic parameters. Participants (4 aphasic with apraxia of speech, 4 with spastic dysarthria, and 15 without speech disorders) performed three different tasks: repeating the syllable sequence [pa-ta-ka], repeating the isolated syllable [pa] and repeating the vowel sequence [i-u]. The results showed that the normative values of motor control, in general, coincide with those obtained in previous research on native English speakers. They also show that damage to motor control processes results in a decrease in the rate of alternating and sequential movements and an increase in the inter-syllabic time for both types of movements. A subset of the acoustic parameters analyzed, those that measure motor planning processes, enable differentiation between normal population and apraxic and dysarthric patients, and between the latter. The differences between the pathological groups support the distinction between motor planning and motor programming as described by van der Merwe's model of sensorimotor processing (1997). PMID- 22774425 TI - Number processing and calculation in Brazilian children aged 7-12 years. AB - Numerical cognition is based on two components - number processing and calculation. Its development is influenced by biological, cognitive, educational, and cultural factors. The objectives of the present study were to: i) assess number processing and calculation in Brazilian children aged 7-12 years from public schools using the Zareki-R (Battery of neuropsychological tests for number processing and calculation in children, Revised; von Aster & Dellatolas, 2006) in order to obtain normative data for Portuguese speakers; ii) identify how environment, age, and gender influences the development of these mathematical skills; iii) investigate the construct validity of the Zareki-R by the contrast with the Arithmetic subtest of WISC-III. The sample included 172 children, both genders, divided in two groups: urban (N = 119) and rural (N = 53) assessed by the Zareki-R. Rural children presented lower scores in one aspect of number processing; children aged 7-8 years demonstrated an inferior global score than older; boys presented a superior performance in both number processing and calculation. Construct validity of Zareki-R was demonstrated by high to moderate correlations with Arithmetic subtest of WISC-III. The Zareki-R therefore is a suitable instrument to assess the development of mathematical skills, which is influenced by factors such as environment, age, and gender. PMID- 22774426 TI - A comparative study of general intelligence in Spanish and Moroccan samples. AB - The aim of this study is to fill a gap in intelligence research by presenting data for the average IQ in Morocco and for a comparable sample in Spain. Adult samples were administered the Raven Standard Progressive Matrices (SPM) (Raven, Court, & Raven, 2001) and scored for the total test and for the three sub-factors of gestalt continuation, verbal-analytical reasoning and visuospatial ability identified by Lynn, Allik, and Irwing (2004). The total test and the three factors have shown satisfactory reliability. Our results for the Moroccan sample show significant relationship between general intelligence factor, gestalt continuation and visuospatial ability with education level and income. Conversely, these variables have been shown to be independent for the Spanish sample. This sample obtained significantly higher scores for the four factors assessed than the Moroccan one. These differences have been found also comparing samples with the same education levels. Finally, the errors percentage for Moroccans has been higher than for Spaniards in all the items, suggesting that the level of difficulty was higher for the Moroccan sample. PMID- 22774427 TI - Text anxiety in adolescents: the role of self-criticism and acceptance and mindfulness skills. AB - The current study sets out to explore test anxiety in adolescent students. The effect of sociodemographic variables on test anxiety was controlled for and the relationship between test anxiety and other psychological constructs, such as self-criticism, social anxiety, acceptance and mindfulness, was examined. In addition, the predictive effect/power of these variables was analyzed and a comparative study between high and low test anxiety adolescents was conducted. Participants in this study were 449 high school students, 211 boys and 238 girls, with a mean age of 16.28 years. These participants completed a battery of self report questionnaires composed by the Portuguese versions of Test Anxiety Inventory (TAI), Child Acceptance and Mindfulness Measure (CAMM), Forms of Self Criticizing/Attacking and Self-Reassuring Scale (FSCRS), and the Social Anxiety and Avoidance Scale for Adolescents (SAASA). Results showed that gender, self criticism and competencies for acceptance and mindfulness had a significant and an independent contribution on the prediction of test anxiety. The comparative study revealed that adolescents with high test anxiety score significantly higher in negative forms of self-criticism, social anxiety and lower in self reassurance, acceptance and mindfulness, when compared to those with low test anxiety. Despite its exploratory nature, the current study adds to the existing knowledge on the influence of psychological processes, such as self-criticism and acceptance, on test anxiety. These findings might constitute a relevant contribution to psychological intervention with adolescents. PMID- 22774428 TI - Research participation improves student's exam performance. AB - Although there have been several attempts to explore for beneficial effects of research participation in social sciences, most of them have mainly explored satisfaction and students learning perceptions (e.g., Bowman & Waite, 2003). Very few works have studied learning by measuring exam performance. Moreover, participation has been usually conceptualized as a mixture of active and passive participation, including in the same measure different practices such as filling up questionnaires, running experiments or reading and answering questions about a journal article or a scientific conference. The present work tries to determine if there is an advantage due to research participation comparing exam performance, satisfaction and perceived learning of the matter Research Methods in Psychology, in three different groups (non-participating, passive and active participating). As we can see in the results, the mere participation benefits exam performance. Results are discussed in terms of the use of research participation as a new powerful active method in education. PMID- 22774429 TI - The benefits of chess for the intellectual and social-emotional enrichment in schoolchildren. AB - This paper examines the benefits of regularly playing chess for the intellectual and social-emotional enrichment of a group of 170 schoolchildren from 6-16 years old. It is based on a quasi-experimental design, where the independent variable was the extracurricular activity of chess (n = 170) versus extracurricular activities of soccer or basketball (n = 60). The dependent variable was intellectual and socio-affective competence, which was measured by an IQ test (WISC-R), a self-report test (TAMAI) and a hetero-report questionnaire (teacher tutor's criterion) applied at the beginning and the end of the academic year. In contrast to the comparison group, it was found that chess improves cognitive abilities, coping and problem-solving capacity, and even socioaffective development of children and adolescents who practice it. The results are modulated, particularly in the area socioaffective, by the personal profile of students who choose practice this activity. PMID- 22774430 TI - Assessment of a sexual coercion prevention program for adolescents. AB - This study's focus is to evaluate a sexual coercion prevention program in adolescents. Using a before-and-after design with both a treatment group (n = 93) and a control group (n = 76), an intervention of seven sessions was completed. Said sessions included such content as conceptualizing sexual freedom, sexual coercion and voluntary consent, analyzing different sexual coercion tactics and the contexts in which they occur, empathy toward the victim, and developing abilities to avoid risky situations. Other risk factors for coercive behavior and sexual victimization are explored as well, such as alcohol use, sexist attitudes and inadequate communication, among others. The intervention's results include a decrease in stereotypical beliefs about the opposite sex and increased empathy toward victims of sexual coercion. These changes were maintained with the passage of time. Also, in the treatment group, a more acute decline was observed in the proportion of young people engaging in sexually coercive behaviors, This article emphasizes the importance, necessity and efficacy of such interventions, and discusses and analyzes possible improvements to the program for its future implementation. PMID- 22774431 TI - Variables associated with the nature of sexual abuse to minors. AB - This study analyzes the prevalence and characteristics of childhood and adolescence sexual abuse suffered by a sample of university students, as well as the variables associated with the nature of abuse. Participants anonymously completed the Questionnaire on Child Sexual Abuse, in order to obtain information about experience of sexual abuse. Of a total of 2,375 students, 289 (12.2%) declared having suffered sexual abuse before the age of 18. The invasiveness, continuity, and severity of abuse was related to the location where the abuse took place (the more severe cases were committed in the homes of the victim and perpetrator) and to the circumstances of abuse (relationships with partners/at a party or while caring for a child predicted more severe abuse). The age of the victim (preschool) and an intrafamilial relationship between victim and perpetrator were also related to more invasive, continuous, and severe sexual abuse. The knowledge of characteristics of perpetrator and victim and the context in which sexual abuse occurs can help to better comprehend the nature and correlates of sexual abuse. The results of the present study may contribute to the design of programs for the prevention of sexual abuse to minors. PMID- 22774432 TI - Parent involvement in school: English speaking versus Spanish speaking families. AB - The purpose of the present study was to explore the relationships between three predictor variables (attitude toward school, parent-child communication, and school commitment action) and the criterion variable (parent involvement) in a representative sample and to examine if these relationships were consistent across three groups (English speaking Caucasian family, English speaking Latino family, and Spanish speaking Latino families). Using a national database (N = 9.841), multi-group SEM analyses were conducted to investigate the relationship between three predictor variables and the criterion variable in three family groups. While all three predictor variables significantly predicted parent involvement in English speaking Caucasian and Latino families, only two variables (parent-child communication and school commitment actions), significantly predicted parent involvement in Spanish speaking Latino families. The results of this study suggest that when administrators, teachers and counselors in school strive to share specific school-related information with Latino families, Spanish speaking families are more likely to become involved with schools. PMID- 22774433 TI - Parental socialization styles, parents' educational level, and sexist attitudes in adolescence. AB - The aims of this study were to analyze the differences in the mothers' and fathers' socialization styles depending on their children's sex; whether there are differences in hostile, benevolent, and ambivalent sexism, and neosexism as a function of both parents' socialization styles; and whether the parents' educational level affects their level of sexism and their children's sexism. The sample included 1,455 adolescents and their parents (764 mothers and 648 fathers). The results showed no differences in the socialization style of the father with his children's sexism, but the mother used a more authoritarian style with her daughters. The parents' socialization style had little influence on their children's sexism, although it had a higher impact on the sons' sexism. The father's style had less influence than the mother's on their sons' sexism, and it had no influence on their daughters' sexism. The indulgent style of both parents had the highest relation with a low level of sexism. Moreover, a negative correlation was found between the parents' educational level and their level of sexism, as well as between the mother's educational level and her daughters' sexism. To conclude, the indulgent style and the mother's high educational level promote fewer sexist attitudes. PMID- 22774434 TI - Self-recognition and self-regulation: the relationship with socialization trajectories and children's sex. AB - The initial process of self development involves interaction with others and the establishment of relationships taking different paths depending on the socio cultural context. Self-recognition and self-regulation are considered manifestations of this development between 18 and 24 months of age. This study aimed at analyzing the relationship between these two aspects, maternal beliefs about autonomy and relatedness, as well as identifying differences between boys and girls in this developmental stage. Participants were 94 mothers of different educational levels and their children of 17-22 months of age in two Brazilian cities. Socialization Goals Inventory and Parental Practices in the First Year Inventory were used to collect data on mothers' beliefs. Children performed tasks related to self-recognition (the mirror test) and self-regulation (compliance to requests). The group of mothers studied valued both autonomy and interdependence. Children's responses are consistent with a perspective of relational autonomy, which value both independence and interdependence. Differences were found in relation to sex in both self-recognition and self-regulation, and baby girls showed superior performance than boys in both tasks. PMID- 22774435 TI - Morningness-eveningness and health-related quality of life among adolescents. AB - Accumulating evidence suggests that evening-type adolescents are exposed to a number of determinants that might have a negative impact on their health condition. Given that few studies have investigated the association between chronotype and quality of life measures in large samples of adolescents, the aim of this study was to assess the relationship between morningness-eveningness and health-related quality of life among 1600 adolescents (aged 12-16 years). Adolescents completed the Vecu et Sante Percue de L'adolescent (VSP-A) and the Morningness-Eveningness Scale for Children (MESC). Girls and older adolescents reported worse health indicators and were more evening oriented. Evening-type adolescents obtained lower scores on vitality, physical and psychological well being, body image, relations with parents, relations with teachers, school work and global health scale. PMID- 22774436 TI - Self-perceptions, self-worth and sport participation in adolescents. AB - The purpose of this study was to study the associations between specific self perceptions and global self-worth with different frequency levels of sport participation among Spanish boys and girls adolescents. Students (457 boys and 460 girls) completed the Self Perception Profile for Children (Harter, 1985) and items assessing sport engagement from The Health Behavior in School Children Questionnaire (Wold, 1995). Results showed that some specific dimensions of self perception were related to different frequency of sport participation whereas overall judgments of self-worth did not. Specifically, for boys and girls, higher levels of sport participation were positively associated to Athletic Competence, and for boys were also associated with Physical Appearance and Social Acceptance. The potential implications of domain specific socialisation processes on the configuration of self-perceptions are highlighted. PMID- 22774437 TI - Perceived control and anxiety in Portuguese children. AB - The central role of perceived control in the development of anxiety disorders is proposed by several theoretical models. The main objective of the present study was to examine the relation between perceived control and anxiety in Portuguese school-age children. To accomplish this objective we developed the Portuguese short form of the Anxiety Control Questionnaire for Children (ACQ-C, Weems, 2005; Pereira & Barros, 2010), whose psychometric studies are presented. The sample comprised 238 children, aged 8 to 15 years, from the general population attending Portuguese schools. Children completed measures of perceived control (ACQ-C) and their anxiety (Screen for Child Anxiety Related Emotional Disorders--Revised, SCARED-R). The psychometric studies indicate good psychometric characteristics of the Portuguese ACQ-C short form, in particular a high internal consistency (a = .85) and an adequate temporal stability (r = .60, p = .002). Results show a significant negative association between perceived control and anxiety symptomatology, providing partial support for models that assign a central role to control beliefs in explaining the development of anxiety disorders. These results also suggest the importance of considering the perception of control as a prime target for preventive actions and intervention aimed at reducing anxiety in school aged children. PMID- 22774438 TI - Spanish young adults' perceptions of the costs and benefits of risky driving behaviors. AB - We used an open-ended survey to elicit Spanish young adults' perceptions of the benefits and drawbacks of speeding and not wearing a seatbelt (or helmet). Around half of the sample reported past engagement in these two risky behaviors, although forecasted engagement was low. Past and forecasted risk taking were positively correlated. Participants provided more drawbacks than benefits of each risky behavior. Drawbacks typically referred to a combination of behavioral acts and social reactions (e.g., accident, punishment) that occurred during the journey. By contrast, benefits largely referred to personal effects (e.g., save time, comfort) that occurred after the journey had ended (speeding) or during the journey (not wearing a seatbelt/helmet). These findings contribute to our theoretical understanding of young adults' risk taking on the road, and to the development of road safety programs. PMID- 22774439 TI - A motivational model for environmentally responsible behavior. AB - This paper presents a study examining whether self-efficacy and intrinsic motivation are related to environmentally responsible behavior (ERB). The study analysed past environmental behavior, self-regulatory mechanisms (self-efficacy, satisfaction, goals), and intrinsic and extrinsic motivation in relation to ERBs in a sample of 156 university students. Results show that all the motivational variables studied are linked to ERB. The effects of self-efficacy on ERB are mediated by the intrinsic motivation responses of the participants. A theoretical model was created by means of path analysis, revealing the power of motivational variables to predict ERB. Structural equation modeling was used to test and fit the research model. The role of motivational variables is discussed with a view to creating adequate learning contexts and experiences to generate interest and new sensations in which self-efficacy and affective reactions play an important role. PMID- 22774440 TI - Elucidating the role of recovery experiences in the job demands-resources model. AB - Based on the Job Demands-Resources (JD-R) model, the current study examined the moderating role of recovery experiences (i.e., psychological detachment from work, relaxation, mastery experiences, and control over leisure time) on the relationship between one job demand (i.e., role conflict) and work- and health related outcomes. Results from our sample of 990 employees from Spain showed that psychological detachment from work and relaxation buffered the negative impact of role conflict on some of the proposed outcomes. Contrary to our expectations, we did not find significant results for mastery and control regarding moderating effects. Overall, findings suggest a differential pattern of the recovery experiences in the health impairment process proposed by the JD-R model. PMID- 22774441 TI - "Having it all": women's perception of impact of female promotion on threat of domestic violence. AB - This study involved 219 women participants. The main aim of the present study is to examine the perceived consequences of a work-related promotion for the female partner in a heterosexual relationship. The impact of the promotion was manipulated - both partners share paid and domestic work, the male partner taking responsibility for all the domestic work - or female partner continuing to do all the domestic work, as well as the male partner's sexist ideology. Finally, the study examined gender ideology of participants. The results showed that participants felt that violence was more likely when the male partner was presented as sexist and that this was due to a perception of threat on the part of the male partner. PMID- 22774442 TI - The role of personality and intelligence in assortative mating. AB - Assortative mating is the individuals' tendency to mate with those who are similar to them in some variables, at a higher rate than would be expected from random. This study aims to provide empirical evidence of assortative mating through the Big Five model of personality and two measures of intelligence using Spanish samples. The sample consisted of 244 Spanish couples. It was divided into two groups according to relationship time. The effect of age, educational level and socioeconomic status was controlled. The results showed strong assortative mating for intelligence and moderate for personality. The strongest correlations for Personality were found in Openness, Agreeableness and Conscientiousness. PMID- 22774443 TI - About the dark and bright sides of self-efficacy: workaholism and work engagement. AB - Taking the Resources-Experiences-Demands Model (RED Model) by Salanova and colleagues as our starting point, we tested how work self-efficacy relates positively to negative (i.e., work overload and work-family conflict) and positive outcomes (i.e., job satisfaction and organizational commitment), through the mediating role of workaholism (health impairment process) and work engagement (motivational process). In a sample of 386 administrative staff from a Spanish University (65% women), Structural Equation Modeling provided full evidence for the research model. In addition, Multivariate Analyses of Variance showed that self-efficacy was only related positively to one of the two dimensions of workaholism, namely, working excessively. Finally, we discuss the theoretical and practical contributions in terms of the RED Model. PMID- 22774444 TI - Evaluation of the effectiveness of minimum intervention measures on young offenders. AB - The goal of this study was to analyze the recidivism rate in minor offenders to whom a minimum intervention measure was applied after their first felony or misdemeanor, and to determine the variables associated with recidivism. The sample was made up of 154 minors from the province of Santa Cruz of Tenerife (Canary Islands, Spain). The information was collected from the database of the Minors' Court. The recidivism rate depends on the measure imposed, ranging between 14 and 40.6%. The degree of agreement between the Technical Team's proposal and the court decision was 70%. With regard to the variables associated with recidivism, a model was obtained through logistic regression that correctly classified 83.7% of the cases, and was made up of the variables perception of parenting problems, intervention of social services, and social isolation. PMID- 22774445 TI - Screening utility of the social anxiety screening scale in Spanish speaking adolescents. AB - The aim of this study was to analyse the screening utility of the Social Anxiety Screening Scale (SASS/EDAS) in a sample of 227 adolescents with social anxiety disorder and 156 Without it (14-17 years). Results showed that the EDAS subscales (Avoidance, Distress and Interference) scores were reliable in terms of internal consistency (alpha > .80). All the subscales discriminated between adolescents with and without the disorder. They also showed a positive and significant correlation with other empirically validated measures of social anxiety. The three subscales indicated relevant sensitivity (69.16-84.14%), specificity (63.46 66.03%) and areas under the curve (.74-.81%). Binary logistic regression analyses indicated the adequate predictive utility of EDAS subscales, with the Distress subscale as the best diagnostic predictor. The data provide empirical evidence of the usefulness of EDAS as a screener for adolescent social anxiety disorder in terms of reliability, convergent and discriminant validity, diagnostic accuracy and clinical usefulness. PMID- 22774446 TI - The use of a screening device to assess psychopathy in young offenders. AB - The aim of this research was to determine to what extent a psychopath screening device (the APSD) is useful in forensic assessments to predict general and violent offending. For this purpose, a cross-sectional study was done and 238 young people serving a sentence were assessed. The gold standard instrument used to measure psychopathy was the Psychopathy Checklist: Youth Version (PCL:YV; Forth, Kosson & Hare, 2003). The results indicate that the association found between the screening device scores and several indicators of risk is low if compared with those obtained with the PCL:YV, suggesting that it is less useful as a tool in order to predict offending or violent offences. However, an Area Under the Curve of .784 and a validity index of 62.5 support its use as a screening device or as a preliminary approach to assess psychopathy in this population. The usefulness of this instrument to make assessments with young people in the forensic setting is discussed. PMID- 22774447 TI - Risk and protective factors of dissocial behavior in a probability sample. AB - The aims of this study were to know risk and protective factors for dissocial behavior keeping in mind that the self-report of dissocial behavior is biased by the impression management. A probability sample of adolescents that lived in two neighborhoods with high indexes of gangs and offenses (112 male and 86 women) was collected. The 27-item Dissocial Behavior Scale (ECODI27; Pacheco & Moral, 2010), Balanced Inventory of Desirable Responding, version 6 (BIDR-6; Paulhus, 1991), Sensation Seeking Scale, form V (SSS-V; Zuckerman, Eysenck, & Eysenck, 1978), Parent-Adolescent Communication Scale (PACS; Barnes & Olson, 1982), 30-item Rathus Assertiveness Schedule (RAS; Rathus, 1973), Interpersonal Reactivity Index (IRI; Davis, 1983) and a social relationship questionnaire (SRQ) were applied. Binary logistic regression was used for the data analysis. A third of the participants showed dissocial behavior. Belonging to a gang in the school (schooled adolescents) or to a gang out of school and job (total sample) and desinhibition were risk factors; being woman, perspective taking and open communication with the father were protective factors. School-leaving was a differential aspect. We insisted on the need of intervention on these variables. PMID- 22774449 TI - Personality, emotions and coping styles: predictive value for the evolution of cancer patients. AB - This study had a twofold goal: to define differences in psychological aspects between cancer patients and a control group and to explore the predictive value of such aspects for the evolution of the disease two years later. Firstly, personality, anxiety, anger and depression were assessed in both groups. Results of t-analyses revealed significant group differences. In personality, cancer patients had higher levels of neuroticism and lower levels of extraversion, agreeableness and conscientiousness than the control group. In emotional variables, cancer patients had higher levels of anxiety and some aspects of anger, but there were no group differences in depression levels. Secondly, applying a quasi-prospective design, the predictive value of personality, emotions and coping styles for the evolution of cancer (favourable or unfavourable) was explored using generalized linear models and logistic regression. A four-predictor logistic model was fitted: Anger Expression-In, Resignation, Self-blame and Conscientiousness, indicating that the higher Anger Expression-in, Resignation, and Self-blame scores together with a lower Conscientiousness score, the more likely it is for patients' cancer to evolve unfavourably. These results indicate the crucial role of psychological aspects for the evolution of the disease and the need to include such aspects in the design of clinical interventions. PMID- 22774448 TI - Psychosocial predictors of relapse in cocaine-dependent patients in treatment. AB - Relapses in cocaine abusers in treatment are an important problem. The majority of patients are incapable of sustaining abstinence over any length of time. To identify the factors associated to relapses risk in the cocaine use can be an optimal choice to improve the treatment strategies. The aim of this study was to analyze relapse-risk factors in cocaine-dependent patients on treatment. Participants were 102 patients who had begun outpatient treatment at a public health center in Spain. Some functional areas and cocaine use are evaluated for a period of six months. A structural equations model was used to identify possible predictive variables. The results show that social-family environment and economic-employment situation were associated with greater risk of relapse. Likewise, the social-family environment was related to severity of addiction. It is concluded that the incorporation of family intervention strategies and vocational/employment counseling may help to reduce relapse rates in cocaine addicts receiving treatment. PMID- 22774450 TI - The memory failures of everyday questionnaire (MFE): internal consistency and reliability. AB - The Memory Failures of Everyday Questionnaire (MFE) is one of the most widely used instruments to assess memory failures in daily life. The original scale has nine response options, making it difficult to apply; we created a three-point scale (0-1-2) with response choices that make it easier to administer. We examined the two versions' equivalence in a sample of 193 participants between 19 and 64 years of age. The test-retest reliability and internal consistency of the version we propose were also computed in a sample of 113 people. Several indicators attest to the two forms' equivalence: the correlation between the items' means (r = .94; p < .001) and the order of the items' frequencies (r = .92; p < .001). However, the correlation between global scores on the two forms was not very high (r = .67; p < .001). The results indicate this new version has adequate reliability and internal consistency (r(xx) = .83; p < .001; alpha = .83; p < .001) equivalent to those of the MFE 1-9. The MFE 0-2 provides a brief, simple evaluation, so we recommend it for use in clinical practice as well as research. PMID- 22774451 TI - Brazilian-Portuguese empathy quotient: evidences of its construct validity and reliability. AB - Empathy is the ability to read other's mind and understand their intentions. This paper examines the psychometric properties of the Brazilian-Portuguese version of a short form of the empathy quotient (EQ, 15 items). The EQ-15 was administered to 237 participants from the general population from Joao Pessoa, Brazil. Confirmatory factor analyses supported the tripartite model with cognitive, emotional and social empathy factors. In line with other studies, gender differences were only observed for the first two factors, with female participants scoring higher on both, which suggests that the social factor might not constitute a truly dimension of empathy. Strong evidence for convergent and discriminant validity was only observed for the cognitive factor. The poor psychometric parameters of the emotional and social factors are argued to reflect the complexity and contrasting ideas of their items. The possibility of elaborating specific items for the emotional and social factors is also discussed. PMID- 22774452 TI - Cross-cultural confirmatory factor analysis of the CES-D in Spanish and Mexican dementia caregivers. AB - The Center for Epidemiologic Studies-Depression Scale (CES-D) is the most frequently used scale for measuring depressive symptomatology in caregiving research. The aim of this study is to test its construct structure and measurement equivalence between caregivers from two Spanish-speaking countries. Face-to-face interviews were carried out with 595 female dementia caregivers from Madrid, Spain, and from Coahuila, Mexico. The structure of the CES-D was analyzed using exploratory and confirmatory factor analysis (EFA and CFA, respectively). Measurement invariance across samples was analyzed comparing a baseline model with a more restrictive model. Significant differences between means were found for 7 items. The results of the EFA clearly supported a four-factor solution. The CFA for the whole sample with the four factors revealed high and statistically significant loading coefficients for all items (except item number 4). When equality constraints were imposed to test for the invariance between countries, the change in chi-square was significant, indicating that complete invariance could not be assumed. Significant between-countries differences were found for three of the four latent factor mean scores. Although the results provide general support for the original four-factor structure, caution should be exercised on reporting comparisons of depression scores between Spanish-speaking countries. PMID- 22774453 TI - Spanish adaptation of the scale of psychological empowerment in the workplace. AB - The objective of this study is to adapt and translate into Spanish Spreitzer's Psychological Empowerment Scale (1995a). A process of translation and reverse translation was applied to the scale's items, whose psychometric properties were then examined using a sample of 272 professional nurses at public hospitals in the province of Seville. The data were subjected to confirmatory factor analysis. The significance of the factor loadings demonstrated the need to create a new model eliminating one item. The 11-item model was shown to possess adequate construct validity and internal consistency. The results confirm the original, four-factor structure obtained by Spreitzer, with the exception of item 10, and support the utilization of the Spanish version of this scale in the workplace. Future research should more extensively investigate its construct validity, and test the nomological network of the operationalized construct within the field of psychological well-being and in the context of the workplace. PMID- 22774454 TI - Development and validation of the theory of planned behavior questionnaire in physical activity. AB - The Theory of Planned Behavior (TPB) is one of the main theoretical models in the study of the different variables, which influence in the practise of physical activity. The aim in this study was to develop a questionnaire based on TPB in physical activity context providing evidence for the validity of the obtained measures. The instrumental project included three independent studies. The first study entailed the construction and qualitative assessment of the items. In the second study, the analysis of factorial structure was performed by means of exploratory measures, and it showed that the reliability of measures was adequate. The third study provided evidence on the dimensionality of the scale. The confirmatory factorial analysis guaranteed the stability of factorial structure proposed by the TPB and provided evidence for the internal validity of the inventory. Moreover, this study provided evidence of its external validity. PMID- 22774455 TI - Validation of eating disorder examination questionnaire (EDE-Q)--Spanish version- for screening eating disorders. AB - This research examines the internal consistency, convergent validity, and sensitivity, specificity, and positive and negative predictive value of the Spanish version of the Eating Disorder Examination-Self-Report Questionnaire (S EDE-Q), as a screening questionnaire for eating disorders (ED) in a community sample. Participants were 1543 male and female Spanish-speaking students (age range: 12-21 years), who volunteered to complete the S-EDE-Q and the EAT-40. The Spanish version of the Eating Disorders Examination (S-EDE) interview, 12th edition, was administered to 602 of the students. Acceptable internal consistency for the four subscales of the S-EDE-Q was obtained (alpha > or = .74). Corrected point-biserial correlation performed with the 22 items included in the S-EDE-Q subscales showed acceptable values for all the items. The EAT-40 Dieting subscale correlated highly and positively with the four S-EDE-Q subscales (r > or = .70). Acceptable results in sensitivity, specificity, and positive and negative predictive value when compared with the EDE were found. Correlation between S-EDE and S-EDE-Q diagnoses was positive and significant. Overall, results support the psychometric adequacy of the S-EDE-Q as a screening questionnaire for ED in community samples. PMID- 22774456 TI - The Spanish validation of level of expressed emotion scale for relatives of people with eating disorders. AB - Expressed emotion (EE) is considered a general predictor of poor outcome across a range of conditions, including eating disorders, and is valuable in measuring the effect of family interventions. There are no self-report questionnaires validated in Spanish to measure EE among relatives of patients with a psychiatric condition. The aim of this study was to examine the psychometric properties of the Spanish version of the Level of Expressed Emotion scale (LEE) among relatives of eating disorder patients. A cross-sectional study of 270 relatives of patients with an eating disorder was conducted to examine the factor structure, reliability and validity of the LEE scale. Results indicated that the LEE-S (Spanish version) did not correspond to the a priori subscales described in the original version. The refined 45-item LEE-S scale consisted of four factors which explained 25.5% of variance in EE for relatives. Reliability was acceptable (alpha ranged from .73 to .86). The discriminant validity of the subscales was moderately supported by correlations with psychological distress (GHQ-12; rho = .34) and specific caregiving experience (EDSIS; rho = .39). The LEE-S instrument has adequate psychometric properties and may be of value to assess families at risk of a negative emotional climate at home. PMID- 22774457 TI - Reliability and sources of validity evidence of the Oviedo Schizotypy Assessment Questionnaire-Abbreviated (ESQUIZO-Q-A). AB - The main goal of this research was to examine the reliability and different sources of validity evidence of the Oviedo Schizotypy Assessment Questionnaire Abbreviated (ESQUIZO-Q-A) in nonclinical adolescents. The final sample was made up of 1,455 participants, 705 males (48.5%), with a mean age of 15.92 years (SD = 1.18). The internal consistency of the subscales ranged from .62 to .75. The analysis of its internal structure yielded a three-dimensional solution based on the dimensions: Reality Distortion, Anhedonia, and Interpersonal Disorganization. Likewise, the goodness-of-fit indices derived from the Confirmatory Factor Analysis for the hypothesized three-factor model were adequate. The three dimensions of the ESQUIZO-Q-A were significantly correlated with the subscales of the Strengths and Difficulties Questionnaire. The ESQUIZO-Q is a brief and simple self-report with adequate psychometric properties for the assessment of schizotypal traits in nonclinical adolescent populations. Future research should continue to explore the metric quality of the ESQUIZO-Q-A (e.g., sensitivity and specificity) and incorporate the new advances in psychological and educational assessment such as Computerized Adaptive Testing. PMID- 22774458 TI - Changing the general factor of personality and the c-fos gene expression with methylphenidate and self-regulation therapy. AB - A deepening in the biological nature of the general factor of personality (GFP) is suggested: the activation level of the stress system is here represented by the gene expression of c-fos. The results of a single case experimental design are reported. A model of four coupled differential equations that explains the human personality dynamics as a consequence of a single stimulant drug intake has been fitted to psychological and biological experimental data. The stimulant-drug conditioning and its adaptation to the considered mathematical model is also studied for both kinds of measures. The dynamics of the c-fos expression presents a similar pattern to the dynamics of the psychological measures of personality assessed by the GFP-FAS (Five-Adjective Scale of the General Factor of Personality) as a consequence of a single dose of stimulant drug (methylphenidate). The model predicts similar dynamic patterns for both psychological and biological measures. This study proves that describing mathematically the dynamics of the effects of a stimulant drug as well as the effects of a conditioning method on psychological or subjective variables and on gene expression is possible. It verifies the existence of biological mechanisms underlying the dynamics of the General Factor of Personality (GFP). PMID- 22774459 TI - Fungal aerosol in the process of poultry breeding--quantitative and qualitative analysis. AB - BACKGROUND: The aim of this study was to assess fungal air contamination in the processes associated with poultry breeding depending on the season. The evaluation was based on the determined concentrations of fungi and qualitative identification of isolated microorganisms. MATERIALS AND METHODS: The study covered 2 hatcheries and 3 hen buildings. The air was sampled in spring, summer and autumn directly onto a filter using air aspirator. For the quantitative analysis of fungi, the medium MEA with chloramphenicol and streptomycin was used. The qualitative identification of fungi was carried out based on macro- and microscopic analysis. RESULTS: The concentrations of total airborne mesophilic fungi in breeding facilities ranged from 1.22 x 10(3) to 5.87 x 10(5) cfu/m3 with the arithmetic mean value 1.60 x 10(5) cfu/m5. In 45% of the taken samples, these levels exceeded the reference value recommended in Poland for occupational environment exposure. The fungi concentration in the air of poultry houses was significantly modified by season (p = 0.04). A higher concentration of fungi occurred in autumn (p = 0.05). The dominant fungal microflora in the air was composed of molds (88%), with the most prevalent genus Acremonium. Yeasts constituted another 10% of bioaerosol and were mainly represented by genus Candida. The fungal aerosol contained two species qualified to the 2 group of risk--Aspergillus fumigatus and Candida tropicalis. CONCLUSIONS: Facilities of poultry farms are contaminated with high concentrations of fungal aerosols, especially in a colder season, often exceeding the recommended limits. Among the fungi, there are also present pathogenic microorganisms that may pose a risk to farm workers' health. PMID- 22774460 TI - [Assessment of occupational exposure to HBV, HCV and HIV in gynecologic and obstetric staff]. AB - BACKGROUND: The aim of the study was to assess the occupational risk for hepatitis B, C and HIV in gynecologic and obstetric staff in the context of the number of sharps injuries, HBV immunization coverage, compliance with personal protective equipment (PPE) use and reporting of exposures. METHODS: A voluntary anonymous survey was carried out between January-June 2009 in 15 ran domly selected hospitals in West Pomerania, Poland. RESULTS: There were 110 participants (response rate 72%), 88.2% females, 11.8 males (aged 21-60 years; mean, 42 years); 80.9% nurses, 19.1% doctors. Among those 60.9% reported at least one sharps injury in the preceding year (Me = 1, range 1-12), 43.6% worked at least once a year with a recent abrasion or cut on their hands. The respondents reported the most recent injuries being caused by a hollow-bore needle (54.4%), a suture needle (26.5%), and an instrument (19.1%); 82.5% of such incidents went unreported. Compliance with PPE use was high for glove use (92.7%), much lower for protective eyewear (28.7%). Except one participant who reported acute symptomatic hepatitis B in the past (possibly due to previous surgery), all participants reported being immunized with HBV vaccine: 46.8%--took three doses, 48.6%-- a booster and 4.6% ended the regimen on two doses. CONCLUSIONS: Frequent sharps injuries, mostly unreported, work with unprotected recent abrasion or hands' cuts and lack of compliance with PPE use are important risk factors contributing to occupational HBV, HCV and HIV infections among gynecologic and obstetric staff. The risk of HBV infection has been significantly reduced by a complete immunization coverage observed among participants. PMID- 22774461 TI - [The health condition of forest workers exposed to noise and vibration produced by chain saws]. AB - BACKGROUND: Lumberjacks' working conditions are difficult due to the presence of numerous occupational hazards. Physical factors that pose a health risk are noise and vibration produced by chain saws. Excessive exposure of lumberjacks to noise and vibration can lead to the development of hand-arm vibration syndrome and hearing loss. The aim of the work was to analyze the health condition of forestry workers exposed to occupational physical hazards. MATERIAL AND METHODS: A preliminary, questionnaire-based assessment of health status was conducted in 22 chain saw operators. In a group of 15 forestry workers audiometry, vibrotactile perception thresholds and cold provocation test were performed. X-ray diagnostic imaging of upper limbs was also done. At the same time noise and vibration produced by chain saws used in forestry was measured. RESULTS: Vascular or neurological disorders were found in nearly half of tested workers with seniority from 2 to 20 years; 40% of the surveyed was diagnosed with hearing impairment. An 8-hour energy equivalent vibration level measured on chain saws was 4.6 m/s2. An 8-hour equivalent sound pressure level was 99.1 dB(A). CONCLUSIONS: The threshold limit values for noise and vibration are exceeded at woodcutters' posts. There are changes in lumberjacks' health resulting from exposure to harmful physical agents. Preventive actions are urgently needed to be addressed, especially to people employed in single-handed forestry companies. PMID- 22774462 TI - [Chemical hazards when working with solvent glues]. AB - BACKGROUND: Solvent glues are used in a wide variety of industries, e.g., textile, footwear and rubber. The problem of workers' exposure to solvent vapors is rarely tackled within the area of occupational safety and health in small and medium-sized enterprises. MATERIALS AND METHODS: In order to assess exposure to solvents, organic solvents emitted by glues were identified in the samples of workplace air. The concentration of acetone, benzene, cyclohexane, ethylbenzene, n-hexane, methylcyclohexane, butyl acetate and toluene were determined. RESULTS AND CONCLUSIONS: The obtained results evidenced the presence of cyclohexane, ethylbenzene, ethylcyclohexane, heptane, n-hexane, o-xylene, methylcyclohexane, methylcyclopentane, butyl acetate and toluene in workplace air. The concentration of those compounds in workplace air was low, usually below 0.15 of MAC. At some workstations the presence of benzene was also observed. Occupational risk was assessed at workstations where gluing took place. It showed that the risk at those workstations was medium or low. PMID- 22774463 TI - [Analysis of workers' exposure to dust in various chemical industry plants based on measurements conducted by work environment reseach laboratories in Poland in 2001-2005]. AB - BACKGROUND: The aim of this publication is to present the results of a detailed analysis of dust exposure in the production and processing of chemical substances, including the kind of produced materials, workposts and type of emitted dusts. MATERIAL AND METHODS: Data on dust exposure were based on measurements of dust concentrations performed by industrial hygiene laboratories. Their results were obtained from sanitary and epidemiological stations operating throughout Poland. Average concentrations ofinhalable and respirable dust at specific workposts in the chemical industry (including 7 groups) were calculated and the percentage of surveys exceeding hygiene standards was estimated. RESULTS: The analysis included 2800 results of dust concentration measurements. The highest concentrations of inhalable and respirable dust (containing a few percent of silica) and the highest percentage of the results above hygiene standards were observed in the manufacture of basic chemicals The concentration of inhalable dust in this group was 2.83 mg/m3, and the percentage of measurements above hygiene standards--16.57%, while for respirable dust, these values were respectively 0.75 mg/m3 and 27.32%. CONCLUSIONS: Exposure to dust in the chemical industry differs, depending on the type of production. Particularly high concentrations, very often above hygiene standards, were observed in factories manufacturing basic chemicals. PMID- 22774464 TI - [Employees health education--challenges according to the educational level]. AB - BACKGROUND: Article addresses the problem of increasing Polish employees health education effectiveness according to the differences in educational level. MATERIALS AND METHODS: Research model assume that effective method of developing recommendations improving the health education will synthesise scientific findings regarding methodology of conducting such education and knowledge about needs of two target groups: low and high educated employees. Educational solutions were searched in publications related to: health education, andragogy, propaganda and direct marketing. The empirical material used to characterize two target groups came from four research (qualitative and quantitative) conducted by the National Centre for Workplace Health Promotion (Nofer Institute of Occupational Medicine) in 2007-2010. RESULTS: Low educated employees' health education should be focused on increasing responsibility for health and strengthening their self-confidence according to the introduction of healthy lifestyle changes. To achieve these goals, important issue is to build their motivation to develop knowledge about taking care of health. In providing such information we should avoid the methods associated with school. Another important issue is creating an appropriate infrastructure and conditions facilitating the change of harmful behaviors undertaken at home and in the workplace. According to high-educated employees a challenge is to support taking health behaviors- although they are convinced it is important for their health, such behaviors are perceived as a difficult and freedom restriction. Promoting behavior change techniques, avoiding prohibitions in the educational messages and creating favorable climate for taking care of health in groups they participate are needed. PMID- 22774465 TI - [Factors enhancing teachers' occupational wellbeing scale: psychometric analysis]. AB - BACKGROUND: The aim of this work was to elaborate the Factors Enhancing Teachers' Occupational Wellbeing Scale for use with teachers from health promoting schools and to provide its psychometric analysis. MATERIAL AND METHODS: The sample consisted of 270 teachers from the health promoting schools. The instrument consisted of 45 statements divided into five subscales (working conditions, teachers' community, students and parents' community, organization and workload, professional competences), which are measured from two points of view: assessment of a current situation (a 5-point rating scale from 5 (strongly yes) to 1 (strongly no)) and assessment of needs for the improvement (a 5-point rating scale from 1 (no need) do 5 (very strong need)). Psychometric analysis included the assessment of: reliability (using Cronbach-alpha coefficient), theoretical validity (factor analysis with principal axis extraction) and construct validity (using data concerning self-assessment of general occupational being and assessment of general occupational being of other teachers at school, two hypothesis were tested) and unidimensionality (principal component analysis). RESULTS: Cronbach's a for subscales, assessment of a current situation: 0.75 0.86, and for subscales assessment of needs for the improvement: 0.80-0.93. Factor structure of the scale was convergent with the expected one. Construct validity of the subscales was satisfactory--all hypotheses were confirmed. All subscales were also unidimensional. CONCLUSIONS: Psychometric analysis of the scale gave satisfactory results concerning its quality. The scale can be used as a tool in staffs health promotion, especially in the health promoting schools. PMID- 22774466 TI - [Assessment of the Polish occupational medicine service (oms) system made by OMS nurses]. AB - This paper presents the results of an assessment of the Polish occupational medicine service (OMS) system made by OMS nurses. MATERIALS AND METHODS: The survey was carried out on a random group of OMS nurses. RESULTS: OMS nurses form a professional group comprised of rather experienced personnel. In the opinion of almost 70% of respondents the system guarantees good occupational heath care, whereas 20% took the opposite view. The great majority of respondents think that all employees have to undergo mandatory prophylactic examinations. The nurses have rather critical opinion about the legal regulations pertaining to occupational health care--their number and complexity, and also express negative opinion about the quality of cooperation with employers (who are contractors for OMS units). OMS nurses believe that prophylactic examinations are the strongest point of the system. They are often the only opportunity for establishing contact between an employee and a physician and learning about diseases he or she was previously unaware of. CONCLUSIONS: Although the general assessment of the OMS system is rather positive, it is not free of shortcomings. Improvements in such fields as legislation, financing of service, professional attitude towards responsibilities of the OMS staff, cooperation with employers (contractors) and primary health care units would undoubtedly result in even better assessment, and what is more important in better functioning of the Polish OMS system. PMID- 22774467 TI - [Bacillus subtilis a legislative health problem in Poland]. AB - The aim of the paper was to discuss the problems related to the classification of B. subtilis and B. thuringiensis bacteria to the 2nd risk group under the 2005 decree of the Ministry of Health on hazardous biological agents (Law Gazette No. 81, item 716 with later amendments). The decree is a Polish implementation of the Directive 2000/54/EC generally consistent with its recommendations, but in the case of certain microorganisms a separate decision has been taken and having in mind the health of workers, changes in the list of hazardous agents existing in Poland have been made. The paper presents in detail the legal situation in this field, as well as current knowledge about the biology of these microorganisms, their use in the biotechnology industry and related production of allergenic proteins, and their effect on the human health. Placement ofB. subtilis and B. thuringiensis in the 2nd risk group resulted in the interpretative difficulties encountered by employers who use products containing these bacteria, institutions involved in such products trade and inspectorates supervising working conditions. Based on the literature review it is suggested to initiate actions leading to the development of hygiene norms for certain enzymes/bioinsecticides present in the air, the more that the tests to assess air concentrations of some of them are available. This solution would permit to remove B. subtilis and B. thuringiensis bacteria from the 2nd risk group without the risk for the care of workers' health. PMID- 22774468 TI - [Pathogenetic and clinical aspects of diisocyanate asthma]. AB - Diisocyanates are currently the most common cause of occupational asthma in industrialized countries, where its prevalence ranges from less than 5% to 15%. They are mainly used in the production of polyurethane foam, plastic packagings, laminates and polyurethane paints. The diagnosis of diisocyanate asthma is often problematic due to the lack of simple diagnostic or screening tests, uncertainty of underlying mechanisms, and a multitude of other potential occupational and environmental causes of asthma. At present, only a specific standardized challenge test with diisocyanates in concentrations not exceeding the adopted hygiene standards has been found to show a real diagnostic value. The diisocyanate-inducedsensitization, is associated with the recruitment of CD4 T lymphocytes to the lungs and the production of Th2-type cytokines, including IL 4, IL-5 and IL-13. However, clinical studies have suggested that an immunological response to diisocyanates may involve both Th1 and Th2 cells. The development of animal models has been instrumental in furthering the understanding of the pathogenesis of many diseases, including bronchial asthma. Murine models of diisocyanate-induced asthma have proved to be the most useful. Mouse models offer distinct advantages of a better-defined genome than that of guinea pigs or rats and the availability of antibody reagents and transgenic strains to investigate detailed mechanistic pathways. A better understanding of the immunopathogenesis of diisocyanate asthma will hopefully lead to early markers of sensitization and asthma, as well as to a profound comprehension of exposure and host risk factors, both of them should greatly facilitate the development of much-needed diagnostic and preventive strategies for diisocyanate asthma. PMID- 22774469 TI - [Barriers to professional activity among people with cardiovascular diseases]. AB - Cardiovascular diseases (CVD) are a very important issue for the health care system. They are usually chronic diseases widespread in the society that require costly treatment and cause long-term sick absenteeism and partial or total incapacity for work. CVD are one of the most common cause of disability in Poland, therefore they constitute a medical, social and economic problem. Low occupational activity of people with CVD at working age requires special effort to develop and implement methods of their professional activation. A key role in this process should be played by physicians of occupational health services (OHS). In the case of disabled workers with cardiovascular disease, the decision about avoiding professional activity is often medically unjustified. It arises from a lack of sufficient knowledge ofjurisprudence and the fear of both the physician and the employee ofpatient's health deteriorations. Therefore, educational actions addressed to OHS physicians and to the patients are needed to enable the patients with CVD to remain at or to return to work. PMID- 22774470 TI - [XVIII International Symposium on Ergonomics, Work Safety and Occupational Hygiene: "he human factor and work safety and hygiene in agriculture"]. PMID- 22774472 TI - [Body composition and energy metabolism at rest]. AB - Indicators of body composition determined by bioelectrical impedance analysis (total body water, extracellular water mass, intracellular water mass, skeletal muscle mass, soft lean mass, protein, mineral mass, fat mass) were compared with the resting metabolic rate values (RMR). Studies were conducted in adults of different occupations, gender, age, weight and height. In total, the survey involved 180 people, residents of Nizhny Novgorod (70 men and 110 women) aged 17 to 63 years. It was shown that the normalization of the RMR with the parameters of the bioelectrical impedance analysis reduced the scatter of individual values. Comparison of the normalization results allowed us to estimate the interconnection between the RMR and the body composition. It was obtained statistical formulas for the relation of the RMR with the bioelectrical impedance. The greatest effect was found with the normalization of lean mass, as well as intracellular and extracellular water masses. The smallest effect was detected with the normalization of body fat. We obtained statistical formulas for the relation of the RMR with the bioelectrical impedance parameters. The highest correlations were found between the RMR and the lean mass, muscle mass and total water mass, the lowest with the fat mass. Role of the metabolically active tissue in energy metabolism, including the role of the intracellular and extracellular water is discussed. The results confirm the importance of the metabolically active tissues in the formation of the value of the RMR. Identified dependencies and high correlation between the RMR and the bioelectrical impedance parameters allows us to use these as a fast and convenient method for the approximate estimation of the RMR. PMID- 22774471 TI - [Methods of nanoparticles control in food and biological objects. Report 1. Use of microscopic and chromatography investigation methods]. AB - One of the promising applications of modern nanotechnology are food productions, which includes the improvement of food packaging, creation of new forms of nutrients that are characterized by improved assimilation and technological characteristics, quality control through the creation of compact and cheap test kits. All these applications of nanomaterials related to the risks of the possibility of receipt of potentially toxic nanoparticles in the diet. The task of regulation and hygienic standardization requires developing of the methods, their qualitative and quantitative analysis for such complex, multicomponent systems, which are the agricultural commodities and food products. The best hope in this plan are assigned to a group of approaches related to the microscopic visualization of artificial nanoparticles in the biological objects. While the typical size of nanoparticles (<100 nm) are below the theoretical maximum resolution light optical methods, transmission electron microscopy often allows not only to identify nanoparticles on their size and shape, but also a qualitative and quantitative analysis their chemical composition with the use of additional analytical options. Another group of elaborate methods used in solving the problems of qualitative and quantitative analysis of nanoparticles are chromatographic methods, in particular, the exclusion, hydrodynamic, high performance liquid chromatography, and the flow-field fractionation. Limitation of chromatographic approaches related with the need of complex sample preparation, as well as specific difficulties in nanoparticles detecting in chromatographic fractions. Transmission electron microscopy and high-performance liquid chromatography methods are officially recommended in Russia for the analysis of artificial nanoparticles in natural biological systems, including food products. PMID- 22774473 TI - [Effect of titanium dioxide nanoparticles on protein expression profiles in rat liver microsomes]. AB - There was studied an influence of intragastric administration of titanium dioxide (anatase form) nanoparticles (NP) on protein expression profiles in rat's liver microsomes by methods of proteomics. Animals received water suspension of NP in doses from 0,1 to 10 mg per kg body weight intragastrically daily during 28 days. Microsomes were isolated from liver by means of preparative ultracentrifugation. Proteins composition was studied by 2D-electrophoresis in acrylamide gel. Protein spots were identified by MALDI-TOF analysis. The results demonstrated appearance of 53 new protein spots and disappearance of 19 spots in animals subjected to NP irrespective of their dose. In addition 25 new spots appeared and 3 disappeared in higher doses of NP when compared to low dose group and control animals. Mass spectrum analysis showed presence of few polypeptides registered in international database among proteins expressed under influence of NP. One of this dominant expressed proteins corresponded to enzyme glutathione transpherase Mu 2 isoform (M=41,55 kD, pI=8,0). The conclusion was made of well advances of proteomic analysis in artificial NP influences on biosynthetic processes estimation. PMID- 22774474 TI - [The Trp64Arg polymorphism of beta3-adrenoreceptor gene study in persons with overweight and obesity]. AB - The development of obesity is determined by lifestyle and genetic mechanisms. In particular, the polymorphisms in the adrenergic receptor genes (ADRB) have been extensively studied for association with obesity-related phenotypes. ADRB3 is an obvious candidate gene given its involvement in the regulation of lipolysis and thermogenesis. ADRB3 Trp64Arg polymorphism, a missense mutation in the first transmembrane domain of the R3-adrenergic receptor is associated with visceral obesity and insulin resistance in the Pima Indian, French, and Finnish populations. The recent meta-analysis that combined data of 6582 individuals from Japanese populations showed significant association the Arg64 allele with increased BMI. There are tested the polymorphisms in the beta3-Adrenoreceptor (ADRB3) gene in associated with body mass index (BMI), fat mass and biochemical parameters.We have been examined 91 persons from Moscow region with BMI >25 kg/m2. The Trp64Arg polymorphism of ADRB3 genes were genotyped with the use of an allelic discrimination assay. The TaqMan-based real-time PCR method was applied. There have been estimated of anthropometric and biochemicalparameters. The frequencies of the Trp64Trp and Trp64Arggenotypes of ADRB3 gene were 82% and 12%, respectively, the frequencies of mutant allele was 6%. Trp64Arg genotypes of ADRB3 compared to Trp64Trp genotypes had significantly higher body fat percentage (respectively 48,6 +/- 0,96% and 43,8 +/- 1,72%, p<0,05), serum glucose (6,51 +/- 0,18 mmol/l and 5,67 +/- 0,09 mmol/l, p<0,01) and uric acid concentrations (0,46 +/- 0,02 mmol/l and 0,38 +/- 0,01 mmol/l, p<0,05). The test of the ADRB3 gene polymorphisms can be used for the personalization of diet in persons with obesity. PMID- 22774475 TI - [Effects of polyvitamin deficiency on the activity of xenobiotic-metabolizing enzymes in rat liver]. AB - The activity of xenobiotic-metabolizing enzymes was studied in the liver of male Wistar rats, which were fed for 4 weeks diets, containing 100 (control), 50 and 20% of vitamin adequate level. Moderate (50%) polyvitamin deficiency increased activity of EROD (by 13%), MROD (by 34%; p<0,05), 4-nitrophenol hydroxylase (by 16%), 6beta-testosterone hydroxylase (by 17%), UDP-glucuronosyle transferase (by 26%, p<0,05) and quinone reductase (by 55%, p<0,05). Deep (20%) polyvitamin deficiency decreased in liver activity of MROD (to 78% of control level, p<0,05), 4-nitrophenol hydroxylase (to 74%, p<0,05), heme oxygenase-1 (to 83%, p<0,05) and quinone reductase (to 60%, p<0,05). At the same time a 22% increase in the UDP glucuronosyle transferase activity compared to the control group was found; activities of EROD, PROD, 6beta-testosterone hydroxylase and the total activity of glutathione S-transferase were unchanged. Deep polyvitamin deficiency had no significant effect on CYP1A1 mRNA and AhR mRNA level, whereas the expression of CYP1A2 mRNA and CYP3A1 mRNA were decreased to 62 and 79%, respectively, as compared with control. PMID- 22774477 TI - [Dietary fiber content in the various groups of foods of plant origin]. AB - The article presents data on the content of soluble, insoluble and total dietary fiber in foods Russian and CIS countries of origin (528 samples (47 types) of food). Conducted a comparative analysis of these data with data on the content of dietary fiber in analogous products on the European market. Statistical analysis of the results was conducted on a PC program designed to package "Microsoft Excel office 2003", using the library of statistical functions. Comparative analysis revealed significant differences in content of various fractions of dietary fiber in plant food of domestic production compared to similar products of the production of the European Union, particularly Germany, more than 1/3 of the time. These differences can't be explained by analytical errors, because, for the purposes of these studies used the method recommended by the Codex Alimentarius Commission to conduct similar studies. Consequently, the results are directly related to differences in the chemical composition of domestic food products, compared with foreign counterparts, which determines the further development and refinement of existing tables of chemical composition. Thus, our data on the content of soluble, insoluble and total dietary fiber can enhance the chemical composition of Russian food. In addition, studies show once again the need for the Russian Federation of their own, national tables of chemical composition of foods, consistent with modern scientific and technological level of development. PMID- 22774476 TI - [Characterization of silver nanoparticles migration from package materials destined for contact with foods]. AB - There was studied migration of artificial silver nanoparticles from polyethylene films destined for package of such foods as bread and poultry into model media reproducing physico-chemical properties and composition of said products. Modification of films was performed by 5- or 10-fold spraying of silver nanoparticles on the surface of package material. Model media were composed from water, alcohol and plant oil according to US FDA and Russian Federal Service for Surveillance of Consumer Rights Protection and Human Well-Being official recommendation. Nanoparticles were detected in model media by means of transmission electron and atomic force microscopy. Quantification of silver in nanoparticles migrating from films was performed by mass-spectrometry with inductively coupled plasma. The results obtained showed that silver migrated from films into test media in form of nanoparticles with mean diameter close to 10-20 nm. Migrated particles were partially aggregated to complexes with dimension about 50 nm with degree of aggregation depending on media composition. Quantification showed that amounts of silver nanoparticles migrating in foods did not exceed save level of this nanomaterial consumption even in aggravated conditions when almost all volume of product was consumed in form packaged in films modified with nanosilver. PMID- 22774478 TI - [Hygienic assessment of food products in Krasnoyrsk region]. AB - This article presents data on the prevalence of different types of sanitary violations, caused by failure to comply with sanitary regulations, on 573 enterprises that produce bakery products, confectionery, dairy, meat and fish products, drinks in the Krasnoyarsk Territory. It is shown that the greatest number of sanitary offenses are committed at manufactures of milk, fish and meat products. Finished goods at 21-37% of these enterprises do not meet the requirements of hygiene standards. The proportion of deposits of factors (such as type of food product, a form of ownership of the enterprise, the type of locality, where manufacture is) in the frequency of sanitary violations has been determined. PMID- 22774479 TI - [The experimental model of alimentary polyhypovitaminosis of different degree in rats]. AB - A model of the alimentary polyhypovitaminosis varying degrees basing on partitive simultaneous reduction of all vitamins in rats diet has been proposed. The model has a principal difference from other experimental models, based on complete exclusion of 1 or 2 vitamins from animal diet. The proposed model allows you to get as close to the actually observed combined deficiency of several vitamins among the population. 5-fold decrease of vitamin mixture resulted in the fact that animals received 20-23% of vitamins D, A, B2, 33% of vitamin B1 and 57% of vitamin E from the content of these vitamins in the diet of animals from control group because of some nature vitamins contained in such diet basic components as casein (vitamins D, A, B1, B2) and sunflower oil (vitamin E). After one month treatment a deep deficiency of all vitamins has developed in rats from this group. Liver level of vitamin A decreased 8,5-fold, vitamins E and B1 - approximately 2-fold, vitamins C and B2 by 22%. Urinary excretion of vitamin B1 and B2 declined 2 and 5,3 fold. Blood plasma concentration of vitamin A decreased 1,9 fold, and E - 1,4 fold, B2 - by 30%. Activities of blood plasma vitamin B6 dependent enzymes reduced 1,4-fold. 2-fold decrease in the amount of vitamin mixture ensured intake about 50-59% of vitamins D, A, B2, and B1 and about 71% of vitamin E of those contained in the diet of animals from control group. Vitamin status indexes of these animals occupied an intermediate position. They have developed a moderate deficit of these essential micronutrients. The proposed model may be useful for metabolic disorders identification, the study of vitamins and minerals assimilation, investigations of the influence of biologically active components of food on these processes, as well as the development of personalized approaches to the correction of vitamin insufficient accuracy. PMID- 22774480 TI - [Clinical analysis of effectiveness of nutritional factor utilization in patients after operation on the gastrointestinal tract]. AB - The analysis of use of a basic clinical nutrition with inclusion to its structure of nutritious mixes after operation on a gastroenteric path at patients is carried out. He allows to predict possible consequences stressful impacts of surgical intervention and an alimentary deprivation, and also to develop ways of their elimination and regulation in an organism. The prognostic interrelation between level of survival rate and indicators of clinical, biochemical and anhropometric researches is established. Clinical manifestations of the postresection diseases, being characterized permanent diverse functional changes, are connected not only with operational intervention and length of rehabilitation period, but also with nutritional disorder of the patient that leads to albuminous, lipid and mineral disorder, vitamin insufficiency and lengthening of rehabilitation period. The correlation analysis showed that decrease in level of a visceral pool of serum proteins in patients after operations on a gastrointestinal tract associated with the high risk of complications, increases of lethality and duration of rehabilitation period. Inclusion of nutritious mixes in a basic clinical nutrition allows to do leveling the deficiency of energy and plastic substances which is observed in the operated. PMID- 22774481 TI - [Medical-biological approach to development of feeding ration for sportswomen- members of Russia weight lifting team]. AB - Physical status of 12 sportswomen - member of Russia weight lifting team during training period was analiysed. Anthropometric, bioimpedance methods with analyzer ABC-01 "Medass" in observation [body weight Index (index Ketle-2), waist circle/hip circle index] and body compositions were used (adipose, bone and muscle tissues masse). Data obtained when bioimpedance method was used indicated: normal body weight and relative adipose mass to body weight - in 92%, surplus - in 8% of cases; body weight Index and normal level of adipose mass - in 75%, surplus - in 25%; active cellular mass and bone mass and general body liquid were found to be normal. 14-day feeding ration for sportswomen were analysed and 3 times per day food intakes was found to be not optimal. Data obtained let to recommend set of daily food products to compose optimal ration for present sportswomen group when energetic value of 4500 kKal and high nutritional value would be provided. PMID- 22774482 TI - [Immune dysfunction in highly skilled athletes and nutritional rehabilitation]. AB - The present review examines the effects of strenuous and moderate exercise on various components of the immune system including humoral and cell immunity. Acute exercise have been found to affect lymphocyte subsets, immunoglobulin levels, the activity of mononuclear phagocytic system, polymorphonuclear leukocytes and cytokine levels, especially IL-1, IL-2, IL-6 and TNF. The extreme type of immune deficiency in sportsmen, in which there are not determine different isotypes of immunoglobulins, there are described as phenomenon of Ig disappearance. The immune suppression is associated with an increased risk of subclinical and clinical infection in athletes. The mechanisms immunodeficiency are multifactorial and include neuroendocrinologocal and metabolic disorders. The immunosuppression in sportsmen may be prevented by use of special diets. Although athletes need to eat a well-balanced basic diet, there are several nutritional factors that are difficult to obtain at a sufficient level from a normal diet since athletes require more nutrients than the recommended daily allowances. Thus, appropriate nutrition enrichment of special products and food supplements containing proteins, amino acids, carbohydrates, vitamins, minerals, antioxidants, probiotics is an essential prerequisite for effective improvement of athletic performance, recovery from fatigue after exercise and ward off immunodeficiency. PMID- 22774483 TI - [Current approaches to assessment of left ventricular hypertrophy. Aspects of differential diagnosis]. AB - Recommendations are proposed how to assess left ventricular hypertrophy (LVH) as well as a complex approach to examination of the heart structure and function in patients with different diseases accompanied with LVH development. LVH differential diagnosis is considered in arterial hypertension (AH), hypertrophic cardiomyopathy (HCMP), accumulation myocardial diseases, non-compact myocardium, valvular and combined cardiac pathology, compensatory LVH in athletes. Novel echocardiological techniques are recommended for use in complicated diagnostic cases. Normal parameters and criteria of LVH severity by thickness of the wall and left ventricular indexed mass according to the latest recommendations of the European and American echocardiology associations are listed. PMID- 22774485 TI - [Pulmonary artery thromboembolism: factors of prehospital overdiagnosis]. AB - AIM: Detection and analysis of factors of pulmonary artery thromboembolism (PATE) overdiagnosis in a prehospital setting. MATERIAL AND METHODS: A total of 102 patients with prehospital diagnosis of PATE entered the study. Prehospital clinical and ECG picture was compared in groups of verified PATE (n=61) and rejected PATE (n=41). Clinical probability of PATE was assessed retrospectively according to Revised Geneva Score (RGS) scale. In 47 cases the analysis was made in dynamics (in 92 +/- 42.1 min, on the average). RESULTS: In the group of patients with false-positive PATE diagnosis we significantly more frequently observed angina-like chest pain and satisfactory condition at examination, ECG evidence for right heart overloading (the most significant marker S(I)-Q(III); p=0.009) occurred less often, mean heart rate was significantly lower than in patients with verified PATE (85 +/- 23,8 and 100 +/- 23,0 b/min, respectively; p = 0,007). Low probability of PATE by the RGS scale was stated in 37% patients from the group with false-positive diagnosis and only in 8% patients with a verified diagnosis of PATE (p = 0.0005). CONCLUSION: Prehospital PATE overdiagnosis can be explained by non-specificity of clinical and ECG picture of the disease in acute period. Application of the RGS scale is effective for objective assessment of the condition and accurate diagnosis. PMID- 22774484 TI - [Community-acquired pneumonia: comparison of etiological diagnostic methods in clinical practice]. AB - AIM: Comparison of different methods of community-acquired pneumonia (CAP) etiological diagnosis. MATERIAL AND METHODS: A total of 20 male and 10 females patients 21 to 75 years of age entered the trial. All of them had CAP running a non-severe course. Microbiological and molecular-genetic methods were used to examine the patients' sputum, blood serum serological tests were made to measure the level of IgM and IgG antibodies (AB) to Chlamydophila pneumoniae and Mycoplasma pneumoniae. RESULTS: Pathogens were detected in 23 (76.7%) patients. Microbiological examination (MBE) detected monobacterial contamination in 19 patients, polymerase chain reaction (pCR) identified monobacterial infection in 10 patients, mixed bacterial infection in 5 and viral-bacterial mixed contamination in 4 patients. MBE provided 19 positive results, PCR - 30 ones. Serological examination detected IgM AB to Mycoplasma pneumoniae in 6 patients, sputum investigation with PCR detected the pathogen only in 2 patients. IgM AB to Chlamydophila pneumoniae were detected in 4 patients, PCR failed to detect infection agent. CONCLUSION: Current etiological diagnosis can be made with the highest efficacy with combination of three methods: microbiological -for detection of bacterial pathogens (except atypical agents), molecular-genetic--for identification of both bacterial and viral pathogens and serological--for diagnosis of atypical pathogens. PMID- 22774486 TI - [Left atrial deformation in hypertensive patients with aortic stenosis and left ventricular hypertrophy of different severity]. AB - AIM: To study left atrial (LA) deformation in patients with arterial hypertension, aortic stenosis (AS) and left ventricular hypertrophy (LVH) of different severity. MATERIAL AND METHODS: LA deformation was studied in 20 healthy subjects and 68 patients. Of them 30 patients had AH and mild LVH, 22-AH and manifest LVH, 16 patients had AS. Standardechocardiography (EchoCG) was made and then analysed with the method of two-dimentional seroscale deformation (TDSD). Segmentory maximal deformation was estimated in 5 middle segments of left atrial walls, middle maximal deformation was determined in 4- and 2-chamber positions, global maximal deformation were evaluated in left atrial contraction and accumulation phases. RESULTS: Due to pressure-induced overloading, LVH was accompanied with abnormal left atrial deformation, AH patients demonstrated decreased deformation even in mild LVH. AS was associated with most pronounced changes of left atrial deformation. Abnormal left atrial deformation in AH and AS was more significant in accumulation phase. In contraction phase, left atrial deformation deterioration occurred only in AS. CONCLUSION: Conduction of TDSD enables analysis of atrial deformation and opens wide perspectives for further investigations aimed at better understanding of changes in the atria. PMID- 22774487 TI - [Characteristics of diagnostic approach to erythrocytosis of different genesis]. AB - AIM: To show distribution of the investigated patients into diagnostic groups, find out the diagnostic value of the levels of hemoglobin and packed cell volume as possible markers of absolute erythrocytosis in the group of patients with polycythaemia. MATERIAL AND METHODS: We evaluated 61 patients, mean age was 46 years (18-82), 9 females and 52 males before treatment. Mean levels of hemoglobin in females - 171 g?l (143-190), packed cell volume 52% (49-61). Mean levels of hemoglobin and packed cell volume for males were 187 g/l (168-196) and 57,8% (49 65), respectively. All blood samples were taken in the morning. Full blood picture of venous blood was determined by Coulter principle on Gen S ("Beckman Coulter", USA) blood analyzer with preserving agent (ethylene diamine tetraacetate, EDTA). Red cell mass and plasma volume were measured by the radionuclide method (Cr-51). Results were performed with an allowance for patient's surface area and were interpreted according to International Council for Standardization in Haematology guidelines (ICSH) (Pearson et al. 1995). RESULTS: Polycythaemia vera was detected only in 19 (31%) among 61 patients, 15 patients refused from further investigation. Among others 46 patients 14 subjects had secondary erythrocytosis, among them 9 were diagnosed with absolute erythrocytosis (hypoxic) and 5 with idiopathic erythrocytosis. Relative ("apparent") erythrocytosis was detected in 13 cases. Measurement of red cell mass allowed us to divide patients into groups with absolute and relative erythrocytosis. Such laboratory parameters as hemoglobin, number of red blood cells and packed cell volume do not always completely show the level of red cell mass due to possible variations of the plasma volume and can not be the reason for diagnosis of haematological disorder. It is shown that hemoglobin level over 185 g/l confirms the presence of absolute erythrocytosis only in 50% of males with polycythaemia, 15% of males with secondary erythrocytosis might have incorrect diagnosis as though increased red cell mass. Statistically defined highly significant (p=0,001) difference of the level of red cell mass in males with polycythaemia and patients with "apparent" polycythaemia turned out to 166% and 111%, respectively. The levels of red cell mass in patients with polycythaemia confirm absolute erythrocytosis over superior normal limit (more then 25%) in comparison with secondary erythrocytosis where red cell mass rate remained normal. Average plasma volume measurements in the same groups of patients were at normal range - 95% u 81%, respectively. Difference between these mean values was authentically significant. CONCLUSION: Red cell mass and plasma volume measurement is easy and necessary procedure for estimation absolute and "apparent" polycythaemia. Rather common occurrence of different forms of erythrocytosis and in particular "apparent" erythrocytosis must determine certain diagnostic approach according to specific clinical case. PMID- 22774488 TI - [The role of duplex scanning of the carotid arteries in detection of correlations between carotid and coronary atherosclerosis by the results of coronaroangiography in patients with stable angina]. AB - AIM: To determine probability of detection of coronary artery atherosclerotic lesion in coronaroangiography (CAG) depending on the presence or absence of carotid artery (CA) atherosclerosis according to findings of duplex scanning (DS). MATERIAL AND METHODS: Of 851 patients admitted to hospital for coronary heart disease (CHD), 67 entered the trial. The patients were examined with DS of CA, exercise test, CAG. Analysis was made of correlations between detection of atherosclerosis in DS of CA and coronary atherosclerosis in CAG. Odds ratio and their confidential intervals were estimated. RESULTS: Probability of coronary atherosclerosis detection in patients with CA atherosclerosis was much higher than in the absence of CA atherosclerosis by DS findings. CONCLUSION: It is recommended to use CA DS data in selection of anginal patients for CAG especially in cases when exercise test cannot be conducted or is not informative. PMID- 22774489 TI - [Trimetazidine addition to antianginal therapy: effects on efficacy and quality of life in patients with stable angina treated outpatiently]. AB - AIM: To compare effects of original trimetazidine versus its generics addition to antianginal treatment efficacy and quality of life in patients with stable angina (SA). MATERIAL AND METHODS: Twenty patients aged 37-74 years with SA of functional class (FC) II-III received standard SA treatment with addition of trimetazidine generics which were later changed for original trimetazidine. Original trimetazidine effects were examined by frequency of anginal attacks and use of short-acting nitrates, changes in anginal FC and chronic cardiac failure, in quality of the patients' life. RESULTS: SA treatment with hemodynamic drugs in combination with trimetazidine generics was insufficiently effective. Change of the generics for an original drug (preductal MB) raised antianginal treatment efficacy as shown by less frequent anginal attacks (reduction from 9.0 +/- 6.9 to 0.3 +/- 0.6 per a week) and by reduced need in short-acting nitrates (from 9.1 +/ 6.9 to 0.4 +/- 0.6 per week) and significant improvement of the patients' quality of life. CONCLUSION: In combined treatment of SA patients it is more effective to use preductal MB which is an original trimetazidine drug than trimetazidine generics. PMID- 22774490 TI - [Choice of treatment of patients with arterial hypertension: symptomatic and basic, standard and situational]. AB - The article analyses cardiovascular morbidity and mortality with consideration of arterial hypertension (AH) involvement in terms of pathogenesis, chronicity of AH and its complications, causes of target organs affection. Such methods of treatment as symptomatic, basic, standard and situational are reviewed. PMID- 22774491 TI - [Variants of orthostatic hypotension. New classification and diagnostic methods]. AB - The article presents a new classification of postural hypotension (pH) and PH detailed characteristics by parameters of arterial pressure, central and peripheral hemodynamics including cerebral circulation; describes methods of detection of different PH variants; gives original data on modified diagnostic criteria and diagnosis of one of the least studied variants of PH - initial PH. PMID- 22774492 TI - [Wireless ECG transfer and centralized system of ECG analysis and storage. Experience with easy ECG usage in the Russian Cardiological Research Center]. AB - Methods of wire and wireless ECG remote registration anda centralized system of ECG reception, analysis and storage are outlined in the context of setting up computer case history. Qualitative assessment of an algorithm of computer syndromal diagnosis used in the Easy ECG system is presented. The system comprises an ECG recorder digital amplifier and software. The system is easy to use and is recommended for introduction into wide medical practice. PMID- 22774493 TI - [Current recommendations on diagnosis and treatment of pulmonary arterial hypertension]. AB - Pulmonary hypertension is a rather frequent pathophysiological and hemodynamic condition detectable in many clinical situations including pulmonary and cardiac diseases. Pulmonary arterial hypertension (pAH) is a specific clinical group of severe and rare diseases with similar morphological, hemodynamic and therapeutic characteristics. PAH diagnosis is confirmed by catheterization of the right heart. Special pharmacotherapy has been developed of late for PAH-oriented treatment. PAH is a progressive disease and therefore demands continuous monitoring and escalation of pharmacotherapy if therapeutic targets fail to be achieved with monotherapy. Combined treatment of PAH seems to be optimal now. PMID- 22774494 TI - [Exercise tests in unstable angina suspects]. AB - The review is devoted to exercise tests (ET) potential in patients with different forms of coronary heart disease (CHD) exacerbation and suspected unstable angina. It is well known that unstable angina untreated pharmacologically is a contraindication for ET. Of interest in clinical practice is diagnosis, risk assessment and treatment policy in patients with chest pain. The main focus is on ET conduction in unstable angina suspects with low and intermediate risk, on safety and validity of ET conduction in these patients. PMID- 22774495 TI - [Pharmacological correction of heart rate in myocardial ischemia]. AB - Cardiovascular diseases is one of the key causes of lethality in developed countries. Coronary heart disease and arterial hypertension make significant contribution to this lethality. The above two diseases are often accompanied with compensatory acceleration of the heart rate (HR). At the same time long-term tachycardia is an independent risk factor of complications resultant from high consumption of oxygen, disturbed energy metabolism in cardiomyocytes, regress of heart contractility, development of cardiac failure. Heart contraction rhythm depends on electric activity of the sinus node cells which spontaneously generate action potentials (4P) present in all heart compartments and triggering contractile activity of cardiomyocytes. The study of the pacemaker cells (pC) discovered not only mechanisms responsible for AP rise and HR physiological regulation but revealed new ionic channels -f-channels involved in acceleration and lowering of the heart rate. Reduction of current along the f-channels (If current) lowers AP generation in PC and, therefore, HR. Three groups of medicines are now used for HR lowering: beta-adrenoblockers, non-dihydropyridine calcium antagonists and recently introduced into clinical practice innovative drug ivabradin (coraxan) selectively suppressing activity of f-channels of sinus node cells and thus lowering HR. The review analyses differences in mechanisms of a negative chronotropic effect of these drugs. PMID- 22774496 TI - [Role of autoimmune reactions in development of cardiac arrhythmia and conduction disturbances]. AB - Cardiac arrhythmias and conduction disturbances are an important cause of morbidity and mortality in many countries all over the world Etiology of these disorders remains unclear in many patients. Experimental and clinical studies show that autoimmune reactions may be involved in development of arrhythmias and cardiac blocks. Precise identification of an autoantibody-mediated mechanism opens new perspectives in the treatment and prevention of cardiac arrhythmias including use of immunosuppressive agents or removal of autoantibodies by absorption technique. The review focuses on cardiac autoantigens, autoantibodies and their interactions that may be involved in development of cardriac arrhythmias. PMID- 22774497 TI - [The environmental conditions and predictors of formation of the bases for a combination of Diphyllobothrium dendriticum and Triaenophorus nodulosus foci in the flood-river ecosystem of the Angara River]. AB - Investigations were conducted in the context of the landscape-biocenological concept. The formation of water-storage basins in the valley of the Angara River was shown to give rise to the transformation of the morphological structure and hydrological regimen of a landscape, which determined a change in some environmental conditions and factors of a combination of foci and the emergence of others. The morphological structure and hydrological regimen of a landscape, the species composition of ecosystems, the populations of hosts, and their biocenotic relations were transformed due to the direct anthropogenic impact on the landscape. There was an emergence of populations of pathogens, parasitic systems of foci, their functional and spatial structures and a formation of invasion foci as the ecosystems of water-storage basins were transformed. There changes were responsible for the formation of an anthropurgic focus of D. dendriticum and a two-host population-combined natural-anthropurgic focus of diphyllobothriasis - Triaenophorus infection. The susceptibility of hosts, the polyhostality of pathogens, and the mechanisms of their transmission are environmental factors that predetermine the formation of epizootic bases for a combination of foci and, being evolutionally formed and relatively strictly determined, have not undergone cardinal changes in the anthropologically transformed landscape. PMID- 22774498 TI - [Nosoareas of clonorchiasis in the Primorye Territory]. AB - The mammalian liver parasite (Clonorchis sinensis flukes) has spread in the Primorye Territory. The areas of the first intermediate hosts for the parasite mollusks of the genus Parafossarulus have been found to recently become wider south-western predominantly due to lotus acclimatization, resulting in the expansion of a parasite habitation area. The intensity of newly formed foci of clonorchiasis is an order of magnitude greater than that of natural ones and they are a higher hazard since they have formed in the recreation areas used by the population for rest and fishing. The carp is the second intermediate host of trematodes. Patients' medical history data show that European and crucian carps (less frequently skygazer, rudd, gudgeon, minnow) have served as the main sources of human infection with trematodes. PMID- 22774499 TI - [New data on the Irkutsk focus of opisthorchiasis and on the need for its investigation]. AB - The paper gives data on an opisthorchiasis focus in the Taishetsky district, Irkutsk Region. The species affiliation of Bithynia from the Biryusa River basin was established. These mollusks are morphologically close to Opisthorchophorus hispanica (= Bithynia inflata). No O. felineus trematodes were found in the snails examined. Roach, dace, and bream were the second intermediate hosts. Analysis of long-term data revealed that fish and human infection rates have remained comparatively high for almost 20 years. The peak for Opisthorchis infestation in carps were in 1982 (9.3%), 1983 (2.9%), 1998 (5.5%), 2000 (2.5%), and 2007 (5.9%). In other years, fish infection ranged from 0.4 to 1.6%. The performed investigations showed that dace and bream were most infected. Data on the focus area that was 1500 km2 are first presented. The Irkutsk focus of opisthorchiasis is considered to be little studied since there is no evidence (infection rate, prevalence) for mollusks, wild (muskrat, otter, bank vole, fox, wolf) and domestic (dog, pig) animals. The considerable pathogenicity of the parasite and the natural focal pattern of the disease call for regular investigations at all stages of its life cycle: mollusks, fishes, fish-eating mammals, local residents, as well as for comprehensive analysis and elaboration of preventive and controlling measures. PMID- 22774501 TI - [Prevalence of anthropozoonosis in circus animals, birds, and reptiles]. PMID- 22774500 TI - [Dirofilariasis in the Nizhny Novgorod Region]. AB - The paper describes cases of dirofilariasis in the Nizhny Novgorod Region in 2006 2010. During this period 26 patients with dirofilariasis were registered. Their age was 20 to 68 years; the maximum cases (26.9%) were among those aged 50-59 years. Females constituted most cases (70%). In 73% of patients, the helminth was found in different areas of the head, with the predominant involvement of eye lesion (34.6%), in the temple (11.5%), cheek (8%), and nose (8%). Dirofilaria were randomly detected in 2 patients. Helminth migration occurred in 15.3% of cases. No clear seasonality for this helminthiasis was found. Local dirofilariasis was noted in most cases (92.3%). This infection was observed in 13 of 49 districts of the region and in 3 of 8 districts of Nizhny Novgorod. The Nizhny Novgorod Region is situated in a low infection transmission risk area (latitude 54-58 degrees North). However, among 11 areas located in this zone, the Nizhny Novgorod Region registered the maximum cases of dirofilariasis. Dirofilariasis in the Nizhny Novgorod Region shares the manifestations of this helminthiasis in the Russian Federation. PMID- 22774502 TI - [Natural focal tick-borne transmissive infections in the children of Perm Territory: differential diagnosis algorithm]. PMID- 22774503 TI - [Problems in the organization of epidemiological surveillance of natural focal infections and ways of their solution]. AB - The spread of natural focal infections is determined by a set of interrelated and interdependent populations of warm-blooded animals, arthropods, and microorganisms. Real danger to humans makes their foci be included into environmental risk factors in this or that area. PMID- 22774504 TI - [Algorithm for the coproscopic diagnosis of human intestinal parasites]. AB - The purpose of the study was to elaborate a detection algorithm for human intestinal helminth eggs. There is a broad spectrum ofcoproscopic methods recommended for the detection of Opisthorchis eggs in man and animals; these include Fulleborn's method, formalin-ether method, Goryachev's, Katoh's, Kalantaryan's, Shcherbovich's, and Kotelnikov-Varenichev methods. Combined coproscopic methods are significantly more effective in detecting the causative agents of enteric parasitoses than is Katoh's method. Among the considered coproscopic techniques for the diagnosis of human ascariasis, it is most rational to use a combined method for fecal examination, the basis for which is a multicomponent flotation system (such as the author's one). The Kotelnikov Varenichev method is optimal for diagnosing opisthorchiasis. It is optimal to use 2-3 methods of different groups simultaneously for the screening diagnosis of intestinal parasitoses. PMID- 22774505 TI - [Thrombocytic and coagulation hemostasis in pregnant women living in the Ob Irtysh river basin with chronic opisthorchiasis]. AB - Opisthorchiasis that is widely spreading in Russia and CIS countries was and remains a serious social, medical, and scientific problem. Local or imported cases of opisthorchiasis have been notified in 87.6% of the administrative territories of Russia. The world's largest focus of opisthorchiasis is the Ob Irtysh river basin with natural preconditions for its high infection in fish. The main clinical manifestations of Opisthorchis infestation are associated with liver damage caused by the obligate presence of Opisthorchis in the bile capillaries with evolving cholangitis, cholangiocholecystitis, and cholangiopancreatitis. Opisthorchis complicates the course of many diseases, affecting gestation, labor, and postpartum. The state of thrombocytic and coagulation hemostasis was analyzed in different period of pregnancy and postpartum (days 2-4), by using the course of pregnancy in the inhabitants of the hyperendemic focus of Opisthorchis infestation (the Ob-Irtysh basin) as an example. In the newcomers, pregnancy develops in the presence of platelet hyperaggregation and accelerated continuous blood clotting. In pregnant women who belong to native little peoples (Khanty, Mansi), opisthorchiasis induces no significant changes in the hemostatic potential. PMID- 22774506 TI - [The agent Latrodectus and canine paecilomycotic eclampsia as a laboratory model in the survey of treatment for mycoses and parasitic diseases]. AB - The extragent used to prepare a Latrodectus mactans hydrocarbon extract is a multicomponent system composed of alkanes, alkenes, and arenes. More than 100 compounds were identified in the hydrocarbon extract (petroleum). The petroleum matrix of Latrodectus mactans was first obtained to manufacture homeopathic remedies. The authors could prepare the first Russian homeopathic medicine from Latrodectus mactans, which proved to be effective in treating canine eclampsia. Canine experiments provide a rationale for the authors' choice as the only homeopathic remedy among thousand known drugs to treat female eclampsia. It is Latrodectus mactans that is in the list of homeopathic medicines permitted for use in accordance with Order No. 335 (Supplement 2) of the Ministry of Health and Medical Industry of Russia, issued on November 29, 1995. It is manufactured from Latrodectus mactans living in the USA. PMID- 22774508 TI - [Malaria in Greece]. PMID- 22774507 TI - [Procedure for Latrodectus reproduction in the laboratory setting and the preparation of the first Russian matrix from its venom to manufacture homeopathic remedies with antiparasitic activity]. AB - The investigation was undertaken to study the biology and ecology of Latrodectus, the possibilities of its importation to Russia from other countries, to breed Latrodectus in the laboratory setting, and to design the first homeopathic matrix of Latrodectus to manufacture homeopathic remedies. The authors were the first to devise a method for Latrodectus breeding in the laboratory setting of Moscow and its vicinities. The Latrodectus bred in the laboratory is suitable to manufacture drugs and in captivity they do not lose its biological activity. The authors were the first to prepare a homeopathic Latrodectus matrix for homeopathic medicines, by using the new Russian extragent petroleum. Chromatography mass spectrometry was used to identify more than a hundred chemical compounds in the Russian petroleum. The biological activity of the petroleum Latrodectus matrix for the manufacture of homeopathic remedies was highly competitive with that of the traditional Latrodectus venom matrix made using ethyl alcohol. The homeopathic Latrodectus matrix made using glycerol lost its biological activity because of glycerol. The biological activity of homeopathic matrixes made from Latrodectus inhabiting the USA, Uzbekistan, and the south of Russia and from that bred in the laboratory was studied. The homeopathic matrix made from the Latrodectus living in the Samarkand Region, Republic of Uzbekistan, has the highest biological activity. PMID- 22774509 TI - [Mixed infection in Plasmodium falciparum malaria]. PMID- 22774510 TI - [A dirofilariasis focus in the Tula Region in 2011]. PMID- 22774511 TI - [Preparation of a prototype of the anthelmintic mitranox (MCT-31) and evaluation of its therapeutic efficacy in sheep moniesiosis and strongyloidiasis]. PMID- 22774512 TI - [Acute toxicity of salicylanilides having anthelmintic activity]. PMID- 22774514 TI - [Use of an aerosol generator (Guard) to control injurious insects in forestry, agriculture, and medical disinsection]. AB - The Guard aerosol generator is a universal multioperational device without a field-of-use restriction in the application of permitted chemical and biological substances, by combining the function of a controlled dispersion aerosol generator and a remote small- and large-drop sprayer in one mechanism and can use aerosol pesticides. The drop fractionation range is as follows: 3-50, 50-100, 100 300, and 200-400 microm for aerosol, dead water, small-drop, and large-drop spraying, respectively, with smooth and step control of working liquid drops. Treatment using the Guard generator has been shown to be highly effective against agricultural and forestry pests. This paper describes the advantages of the Guard sprayer over those of the conventional air and ground ones. The long-term use of the Guard generator to control mosquitoes and ticks in the Tyumen region could substantially improve the epidemiological situation of tick-borne infections and protect children's recreation centers from attacks of bloodsuckers. PMID- 22774513 TI - [Efficacy of anthelmintic mitranox paste against helminthiasis in sheep]. PMID- 22774515 TI - [The 85th anniversary of N. N. Petrov Research Institute of Oncology]. PMID- 22774516 TI - [N. N. Petrov Research Institute of Oncology: present and future]. PMID- 22774517 TI - [Strategic and practical approaches to solving the problem of breast cancer]. PMID- 22774518 TI - [Molecular diagnostics in oncology]. PMID- 22774519 TI - [Waterborne carcinogens and the problems of cancer prevention]. PMID- 22774520 TI - [Methodologic aspects of assessing the performance of cancer care based on the new developments in information technology]. PMID- 22774521 TI - [Geographical and economic determinants of life expectancy and cancer morbidity in the male population]. PMID- 22774522 TI - [Nuclear medicine in radiotherapy planning for patients with malignant neoplasms of different locations]. AB - The performance of nuclear medicine methods in radiation therapy tactics determination was analyzed in patients receiving therapy for Hodgkin lymphoma (HL, n=556), breast cancer (BC, n=230), treatment-naive patients with non-small cell lung cancer (NSCLC, n=86). In HL patients the nuclear medicine methods were used to determine the irradiation fields for spleen irradiation (67%) and abdominal lymph nodes (27%). The bone marrow scan data had significant influence on radiation therapy tactics in 10-27% of cases. The visualization of primary tumor lymphatic drainage lead to changing the irradiation field topography in 75% cases of external BC and 85% of internal BC localization. Tumorotropic isotope mammal scan data lead to the changes in planned irradiation volume in 16% of BC patietns. In NSLC patients the results of "positive" scintigraphy with lipophilic 99mTc-marked cations lead to the change in irradiation tactics in 16% of cases. Therefore, the results of diagnostic investigations suggest the important role of nuclear medicine diagnostic methods in patients with various tumors of different localizations. PMID- 22774523 TI - [Metformin does not suppress the aromatase expression in breast cancer tissue of patients with concurrent type 2 diabetes]. AB - Although there is data suggesting the in vitro inhibition of aromatase in cell lines by antidiabetic biguanide metformin (MF), there is no data on the intratumoral breast cancer (BC) aromatase expression in patients already receiving therapy for type II diabetes. Paraffinized tumor samples obtained from 57 BC pts aged 48-77 yrs, >80% of pts had stage T1-2N0-3M0 BC. Thirteen of the pts didn't have diabetes, 44 pts were previously diagnosed type II diabetes and reseaved the following therapy for at least 1 year: diet only (n=14), sulphonylurea (SU, n=14), metformin (MF, n=9) or MF with SU (n=7). Tumor samples were deparaffinized in xylene and treated with the monoclonal aromatase antibody 677. The rate and intensity of tissue staining was then analyzed by semi quantitative method using conventional scores. Negative controls were processed with 0.01 M PBS instead of the specific antibody. For positive control paraffin embedded human placenta samples were used. By conventional scores method the following values were obtained: 1.31 (pts without diabetes), 1.47 (all diabetic patients), 2.22 (MF), 1.50 (SU), 1.29 (MF+SU), 1.81 (MF and MF+SU), 1.07 (diet). Allred scores for progesterone receptor (PR) were the highest in the samples from pts treated with MF or MF+SU and the lowest in the samples obtained from SU treated pts. Thus, in contrast to previous findings suggesting the suppressive effect of MF on aromatase in vitro, no such trend was discovered for aromatase expression in tumor samples from diabetic patients treated with MF. Although the investigated patients population is still small, this data combined with clinical data (higher PR levels) may suggest the better responses to hormonal therapy in MF-treated diabetic patients. PMID- 22774524 TI - [Conservative treatment of locally advanced and inoperable esophageal cancer: possible methods and future directions]. AB - This is an analysis of treatment results data for conservative (endosurgical and radiation therapy) treatment of patients with inoperable locally advanced esophageal cancer receiving therapy in 1990-2011. The original treatment tactics including recanalization of tumor-compressed esophageal lumen (argon plasma coagulation +/- high-frequency surgery or chemical tumor necrolysis) with consequent combined radiotherapy resulted in clinical response in 79,5% of cases, 89,3% of patients retained the possibility of enteral nutrition. One-year overall survival (OS) was 68,9% (58,8% in patients receiving combined radiotherapy), 2 year OS was 22,7% and 21,2% respectively. PMID- 22774525 TI - [Current principles and approaches to the treatment for patients with locally advanced rectal cancer]. AB - The short-term treatment results of 91 patients with locally advanced rectal cancer are presented. All patients received surgical treatment and neoadjuvant chemotherapy. The chemoradiotherapy effect was evaluated by comparison of pre- and post-therapeutic MRI data. MRI data was also compared with post-operation tumor morphology data. In 23% of resected tumor samples complete tumor regression was evident, in 47.2% of cases partial regression was revealed. Lymph node metastases were found in 21.9% of cases. The discrepancy in MRI and morphology data can be explained by the limited ability of MRI in differentiation between viable tumor, fibronecrotic tissue and inflammatory reaction after chemoradiotherapy. PMID- 22774526 TI - [Sonographic imaging of soft tissue tumors]. AB - In the course of this study 651 patients with morphologically confirmed soft tissue tumors of different localizations underwent gray-scale sonography, Doppler sonography and energetic Doppler carting. Hitachi HI Vision 900, Logiq-400, Aloka 650, Aloka-2000 scanners wih 5-13 MHz sensors were used. Lipomas, fibrolipomas, benign angioneoplasms and some of the desmoids were shown to have a characteristic sonographical picture. The potential sonographic symptom complexes were determined. Among the malignant tumors the distinct sonographic features were observed in liposarcoma and peripheral nerve sheath tumors. The other soft tissue sarcomas have no characteristic sonographic pattern. In this cases the differential diagnosis could be assisted by clinical signs and medical history analysis. PMID- 22774528 TI - [The role of laparoscopic interventions in diagnosis and treatment of patients with locally advanced cervical cancer]. AB - The efficiency of laparoscopic para-aortic lymphadenectomy and radiodiagnostic methods in pre-treatment clarification of tumor lesion extent in stage IB2-III cervical cancer patients was compared. The Magnetic Resonance or sonographic imaging data was found to be inferior to lymph nodes morphological investigation followed by morphological study of distant lymph nodes. The results demonstrate the adequacy of surgical staging by laparoscopic para-aortic lymphadenectomy in patients with locally advanced cervical cancer for therapy tactics decision making. PMID- 22774529 TI - [Verification of histologic diagnosis in cervical carcinoma in situ with contradictory morphological data]. AB - The medical technology of in situ cervical carcinoma cytological verification using computer-assisted morphometric and density analysis of atypical cells nuclei was developed. The technology is aimed at diagnosis verification in cases with contradictory morphological data. The malignant transformation of cervical epithelium undetectable by conventional morphology methods can be diagnosed using the Felgen-stained samples nuclear DNA distribution data. The right DNA distribution diagram shift with modal class 4C or higher, mean DNA contents higher than 4C, the ratio between aneuploidic and polyploidic cells higher than 0.2 are the signs of cervical epithelium malignant transformation. PMID- 22774527 TI - [Phase II clinical trial of autologous dendritic cell vaccine with immunologic adjuvant in cutaneous melanoma patients]. AB - This paper describes the clinical results and immunologic changes in cutaneous melanoma patients receiving active specific immunotherapy with autologous dendritic cell vaccine (DCV) in combination with cyclophosphamide used as immunologic adjuvant. Twenty eight patients with morphologically verified stage III-IV cutaneous melanoma receiving therapy in N. N. Petrov Research Institute of Oncology between 2008 and 2011 were included in the study. All patients signed an informed consent form. Nineteen patients (67,9%) received DCV in therapeutic setting, 9 (32,1%) received it in adjuvant setting. DCV therapy was well tolerated. No serious adverse events were registered. Frequent adverse events included Grade 1-2 unspecific symptoms (fever, fatigue, flu-like symptoms) observed in 22% patients after 3,5% of vaccinations. In therapeutic settings the use DCV lead to clinical effect (PR+SD) in 36,6% of patients. PR was observed in 5% of (95% CI 0-15%) patients, SD in 31,6% (95% CI 13-56%). Duration of the objective responses was 168-965+days. Addition of immunologic adjuvant (cyclophosphamide 300 mg/m2 IV 2 hours) 3 days before vaccination increased its efficacy. In this patients group (n=12) the therapy lead to clinical benefit in 42% (95% CI 17-69%) of cases, median time to progression was 91 (95% CI 55-126) days. This regimen was selected for adjuvant therapy. In the adjuvant therapy group (n=9) the median time to progression was 112 (95% CI 58-166) days. Immunologic monitoring showed correlation ofT- and B-cell immune response with DCV clinical efficacy (p<0,05), no correlation with delayed hypersensivity reaction was observed (p>0,1). DCV is well tolerated and shows immunological and clinical response in stage III-IV skin melanoma patients. PMID- 22774530 TI - [Prognostic value of human papilloma virus DNA test in patients surgically treated for squamous cell cervical cancer]. AB - The human papilloma virus (HPV) DNA test was performed in paraffinized biopsy samples of iliac lymph nodes obtained from 98 patients with cervical cancer receiving therapy in N. N. Petrov Research Institute of Oncology in 2000 to 2007. The data obtained was compared to patients clinical course. The HPV DNA was detected in 29 of 98 patients samples (29,6%), 27 of those patients had metastatic disease. These patients had significantly higher metastasis rate than HPV DNA-negative patients (p < or = 0,05). The following highly oncogenic genotypes of HPV DNA were detected: type 16 in 15 patients (51,72%), type 18 in 4 patients (13,79%), type 31 in 5 patients (17,24%) and type 33 in 5 patients (17,24%). In all the cases the HPV type detected in the lymph nodes corresponded to the one detected in the primary tumor. The relapse-free survival of HPV DNA positive patients with iliac lymph nodes metastases (N1) was significantly lower than in HPV DNA-negative patients (p < or = 0,05). The iliac lymph nodes HPV DNA detection had 43,6% sensitivity (95% CI: 28/60%) and 79,7% specificity (95% CI: 67/89%) for relapse prediction. The test results had diagnostic value in 65,3% of cases, the test was false-negative in 56,4% and false-positive in 20,3% of cases. PMID- 22774531 TI - [Testicular germ cell tumors, the state of diagnostics and staging in Saint Petersburg]. AB - In the last 25 years germ cell tumors have become one of the few cancers with high cure rate. However, there is a lack of information on testicular germ cell tumors in the male population and even among general practitioners leading to late or false diagnoses. The shortening of timespan between the first clinical signs appearance and diagnoses can result in earlier diagnosis, fewer therapy interventions and better overall survival rates. PMID- 22774532 TI - [The effect of SSH&H on the lifespan and spontaneous cancer development in transgenic mice with HER-2/neu mutation]. AB - 10 months old mice receiving SSH&H with daily food increased the lifespan in comparison to the control group. The maximal lifespan was increased by 1,6 months. For the long-living 10% group the mean lifespan increased by 8,7% compared to the control group (p<0,05). The mammary gland neoplasia rate was the same in both groups. The mean latent tumor development period duration, number and size of the tumors were also similar. There was a tendency to lower lung metastases rate in the experimental group. The cumulative neoplastic frequency curve for the experimental group was shifted to the right in comparison to the control group curve giving evidence to the inhibitory effect of SSH&H on the neoplastic rate in transgenic mice with HER-2/neu mutation. PMID- 22774533 TI - [Inhibitory effect of bioginseng on radiation-induced carcinogenesis in rats]. AB - Influence of bioginseng (biotechnological pharmaceutical drug from ginseng radix culture) on radiation-induced carcinogenesis has been studied. LIO female rats were divided into 3 groups. Rats of the first group (n=25) were used as intact control and weren't exposed to any influence. Rats of the second (n=50) and third (n=50) groups were exposed to single total body gamma-irradiation at a dose of 4 Gy. Animals of the 2nd group weren't exposed to any influence after irradiation, while animals of the 3rd group were given bioginseng with tap water (20 ml/l) until the end of study (438 days). In the control group 22,7% of animals developed tumors. In the 2nd group (irradiated control) 70% of animals were bearing multiple tumors one third of which were malignant. Mammary gland tumors were most frequent. Compared to the 2nd group the 3rd group receiving irradiation and bioginseng demonstrated the decrease in tumor incidence by 24.5% and 2,4 rate of decrease in tumors number. For the malign tumors was observed the decrease by 26.8% and 2,9 times, accordingly. For the mammary tumors the decrease was by 23.0% and 2,0 times, for mammary adenocarcinomas by 23.4% and 3,5 times, accordingly. The incidence and number of endocrine and reproductive organs tumors was 20,9% and 5,6 times, accordingly. Therefore, bioginseng effectively inhibits carcinogenesis induced by ionizing radiation in female rats. PMID- 22774534 TI - [Current problems in the combined therapy of lung cancer]. AB - The paper describes the general experience of modern lung cancer treatment methods application. Neoadjuvant therapy was shown to improve the long-term results of stage III patients increasing the 5-year overall survival by 7,8% (p=0,012). The special diagnostic algorithm for treatment results evaluation including autofluorescence spectrometry with 97,1% sensitivity and 88,3% specificity was developed. The adjuvant external-beam radiotherapy in patients with mediastinal lymph nodes metastases was shown to increase the 5-year overall survival (14,7% versus 19,7%) (p=0,01). The combination of endotracheobronchial surgery with chemoradiotherapy allowed to increase the median survival time of patients with inoperable lung cancer to 17 months. Isolated lung chemoperfusion was shown to increase the overall (p=0,019) and relapse-free (p=0,005) survival in patients with lung metastases. PMID- 22774535 TI - [Concurrent chemoradiotherapy with moderate dose brachytherapy as remission induction for patients surgically treated for esophageal cancer]. AB - The locally advanced cancer of thoracic esophagus was treated by induction chemo irradiation therapy (IHRT) with intraluminal medium dose-rate brachytherapy (IMBT). From July 2009 to February 2012 twenty five patients (mean age 54.3 +/- 1.3 years) were included in the study. The length of the primary tumor was up to 6 cm in 10 pts and more than 6 cm in 15 pts. Induction therapy consisted of three IMBT sessions (7 Gy X 3; q7d) and two cycles of chemotherapy (PF; q28d), 26-31 days later the surgery was performed. Subtotal resection of the esophagus type of I Lewis was performed in 23 pts, transtracheal extirpation of the esophagus was performed in 2 pts.In all the cases 3F lymphodissection was performed. After IHRT in 15 of 25 pts. was obtained complete or partial response, in 10 of 25 pts was obtained disease stabilization. Perioperative complications occurred in 17 (68%) patients receiving conservative treatment, one patient (4%) died of treatment complications. In 6 cases (24%) morphology had shown the complete regression of primary tumor. Thus, the combination of intraluminal medium dose-rate brachytherapy and chemotherapy lead to reduction of primary tumor local spread and can be an efficient factor in improving the results of surgical treatment. PMID- 22774536 TI - [Relapse in Hodgkin lymphoma]. AB - The retrospective study revealed the 15% relapse rate in patients with stage II IV unfavorable prognosis Hodgkin lymphoma, 5-year OS in relapsed patients was 84%. Karnofsky score less than 80 (p=0,0001), more than 1 extranodal lesion (p=0,0004), extensive (equal to stage III-IV) involvement on relapse (p=0,001), b symptoms on relapse (p=0,023), more than 5 lymph nodal lesions (p=0,027), albumin level less than 40 g per liter (p=0,037), detection of new nodal lesions (p=0,041) were shown by discriminative analysis as the therapy effect predictors in patients with Hodgkin lymphoma relapse. In patients with second-line therapy failure the actuarial survival rate was lower by 55% in comparison to patients with chemosensitive relapses (40% and 95%). The secondary therapy resistance was shown to be an unfavorable prognosis predictive factor (p=0,0001). The multifactorial overall survival analysis revealed the following adverse prognostic factors: failure of second-line treatment (p=0,0001), first early relapse (p=0,01), albumin level on relapse less than 40 g per liter (p=0,02), use of standard chemotherapy instead of irradiation (p=0,02). The relapse patients with 1 or less risk factors had 95% 5-year OS, the patients with 3 or more adverse risk factors had 70% OS (p=0,0002). The lowest 10-year OS was observed in patients with 2 or more adverse risk factors, 48% and 28% accordingly. Adverse risk factors must be considered while choosing the optimal treatment strategy aimed at better survival rate. PMID- 22774538 TI - [Perspectives of development in anesthesiology and intensive care in oncology]. AB - Despite of anaesthesiology and intensive care progress in oncology there are some problems that need to be solved. These include low individual significance of perioperative risk scale, the lack of approaches for postoperative correction of risk value, estimation of surgical stress value, approach to detection of pain mechanisms etc. The studies which will resolve these problems allow improving the quality of medical care for cancer patients. PMID- 22774539 TI - [Cutaneous melanoma: clinico-morphological analysis of current diagnostics]. PMID- 22774537 TI - [Organ-preserving interventions in combined therapy of children and adolescents with osteosarcoma]. AB - An analyzed cohort consists of 50 pediatric patients with osteosarcoma receiving combined therapy in N. N. Petrov Research Institute for Oncology (1999-2010). Thirty nine of them had localized disease, 11 patients had distant metastases. The treatment scheme included neoadjuvant therapy with cisplatin and doxorubicin, surgical treatment and adjuvant therapy depended on initial response and could include cisplatin, doxorubicin, high-dose methotrexate, ifosfamide, etoposide. Four-year overall and relapse-free survival in children with localized disease was 74.3% and 69.2% accordingly. In 62% of patients were performed organ preserving surgical interventions, in 22 patients was performed endoprosthetics, in 4 patients the defect was replaced by a bone autograft on a vascular bundle. The effectiveness of initial treatment and secondary endoprosthetics were analyzed. Six patients with lung metastases received normotermic lung chemoperfusion, 4 of them are alive and disease-free for 8 to 24 months. PMID- 22774540 TI - [Immediate results of regional chemoperfusion in treatment of patients with cutaneous melanoma or soft tissue sarcoma of the extremities]. PMID- 22774541 TI - [Morphological and molecular basis for individualized therapy in brain tumor]. PMID- 22774542 TI - [Specific features of the technique of performing coronary bypass operations on the beating heart]. AB - The article presents a technique of performing coronary bypass operations on the beating heart used by the authors in 847 patients which is based on high thoracic epidural anesthesia, primary formation of proximal anastomoses of the aorto coronary bypasses and specified succession of the formation of distal, stabilization of the local part of the heart in the field of placing distal anastomosis and access to the lateral and posterior surface of the heart with vacuum stabilizers, using blower-humidifier and intracoronary shunts. PMID- 22774543 TI - [A comparative assessment of immediate results of correction of mitral insufficiency from the left-auricular and transventruicular accesses in patients with postinfarction aneurysm]. AB - Reconstruction of postinfarction aneurysm of the left ventricle (LV) and plasty of the mitral valve without implantation in combination with coronary shunting or without it were used in 81 patients with ischemic heart disease. Correction of mitral insufficiency was fulfilled in 40 patients by an access via the left atrium, in 41 patients--from the LV in its reconstruction. Lethality in the nearest postoperative period was 3.7%. Mitral insufficiency after operation was absent in 70% of patients with the left atrium access and in 58.5% with the transventricular access, in the rest of the patients the mitral insufficiency was not more than of the II degree. Significant differences between the immediate results depending on the access to the mitral valve were not found. PMID- 22774544 TI - [Ultrasonography in the diagnosis of cholelithiasis and its complications]. AB - The author presents the results of ultrasound investigation (USI) of 419 patients with cholecystocholedocholithiasis. The diagnostic accuracy of USI methods in patients with calculous cholecystitis was 98.8%. Direct signs of visualization of concrements in the common bile duct (CBD) were found but in 68.5% of patients. On the basis of USI results the common bile stones were found in 287 (68.5%) patients. The concrements omitted in transabdominal USI were diagnosed using endoscopic retrograde cholangiopancreaticography, magnetic resonance cholangio pancreaticography, endoscopic ultrasonography as well as in operative intervention. PMID- 22774545 TI - [Balloon-assisted enteroscopy in surgical practice]. AB - The authors analyze their experience with video-capsular enteroscopy and balloon assisted enteroscopy in 184 patients. High diagnostic significance of enteroscopy and the possibility to perform minimally invasive operations are shown. PMID- 22774547 TI - [Urgent operations for diseases of the thyroid gland and postoperative complications]. AB - Anasplastic carcinoma of the thyroid gland (243 cases), polinodous goiter of cervical retrosternal localization (25 cases), acute purulent strumitis or thyroiditis (9 cases) induced disturbance of aero-digestive organs of the neck and resulted in the necessary urgent surgical care. The most dangerous complications after 23777 operations on the TG requiring repeated surgical intervention were bilateral lesion of the recurrent nerves (1% of observations), hemorrhages in the TG bed (0.38% of observations). Timely surgical treatment as well as exact knowledge of the neck anatomy, visual control of the recurrent laryngeal nerves, cover of the nerves and lessening the TG bed volume with a part of the parietal leaf of the 4th fascia of the neck in each thyroid operation considerably decreased the danger of asphyxia and the appearance of life threatening complications at the early postoperative period. PMID- 22774546 TI - [Choice of the method of minimally invasive treatment of high venovenous blood reflux in patients with varicose disease of the lower extremity veins]. AB - An analysis of complex examination and the following treatment of 337 patients with varicose disease was made. According to the results of the examination three groups of patients were established: the first group--of low intensive, the second group--of mean intensive, the third group--of highly intensive blood reflux. The patients of the first group were treated by the method of injection sclerosing therapy. In the second group the sclero-surgical technology was used: after crossectomy into the lumen of the varicosity altered part of the great subcutaneous vein the sclerosing substance was administered through a catheter. In the third group ablation of the great subcutaneous vein of the femur was performed and obturation of the varicosity altered veins of the crus with the autovein ablated from the femur. In the first group recurrent diseases were noted in 9.1%, in the second group--in 9.4%, in the third--in 3% of the patients. PMID- 22774548 TI - [Clinical-radiologic diagnostics of cranio-cerebral injuries in polytrauma]. AB - A retrospective analysis of clinical-radial examination was made in 1946 patients with polytrauma. In 82% of them severe cranio-cerebral traumas and extracranial injuries were revealed. The diagnosis of fractures of the skull bones on the basis of survey radiography was possible but in 2% of the patients. Cranio cerebral and craniofacial traumas appeared much more often than injuries of other anatomical areas, reaching 79.4%. Spiral computed tomography was the main method of early diagnosing polytrauma which allowed detecting the character, localization and volume of traumatic injuries of the skull bones, facial skeleton and brain in shorter terms. The information value of the method was 97%. PMID- 22774549 TI - [Endovideosurgical interventions for thoracoabdominal wounds]. AB - The authors presented results of examination and treatment of 1347 patients with different injuries of the chest and abdomen. Medico-diagnostic measures used in treatment of such kind of patients with rational application of endovideosurgical techniques such as thoraco- and laparoscopy are described which proved to be the final kind of operative treatment. PMID- 22774550 TI - [Specific features of wounds with a self-defense traumatic weapon "Osa"]. AB - Specific features and outcomes of wounds with a traumatic weapon of self-defense "Osa" were analyzed in 24 patients. Mean age of the wounded was from 21 to76 years. In 20 patients there was a single wound, in 4 patients it was multiple, in 7--blunt, in 12--perforating and 5 patients had gutter wounds. All the patients were treated according to the principles of field military surgery. Five patients had severe wounds: penetrating fracture of the skull (2 of them died), fracture of the shoulder (1 case), injury of the main artery (1 case), of the pleura (1 case). The wounds were closed up by primary intention in 19 patients, by second intention in 4 patients. The authors' experience shows that a traumatic weapon of self-defense "Osa" rather often caused permanent harm to health and can be mortal. Active surgical strategy in treatment of such patients prevents the development of serious infectious complications. PMID- 22774552 TI - [Experience with surgical treatment of newborns with necrotizing enterocolitis]. AB - At the period from 1984 through 2010 there were 306 patients with necrotizing enterocolitis aged from 1 to 13 days. Conservative therapy in 214 (70%) cases resulted in favorable outcome of the disease. Operative treatment was necessary in 92 (30%) neonates. In 26 of them double entero-, colostomies were performed, in 7 patients ulcer defects were sutured, in 6 patients parts of intestinal necroses were resected with applying primary end-to-end anastomoses, in 15 patients--laparostomas in combination with intestinal stomas, in 13 patients isolated laparostomas, in 8 patients diagnostic laparotomies. PMID- 22774551 TI - [Endoscopic treatment of children with esophagus stenoses of different etiology]. AB - Nowadays not only diagnostic but also therapeutic interventions are widely used in pediatric endoscopy. The authors analyze 25 cases of esophageal stenosis of different genesis (caustic, peptic, anastomotic and congenital esophageal obstructions) in children aged from 1.6 to 15 years. The endoscopic treatment was successfully performed by mechanical dilators with a guidewire and balloon dilator in all patients. The age less than 2 years, previous complications, subtotal stenosis can not be considered absolute contraindication for endoscopic treatment. PMID- 22774554 TI - [Application of a device for determination of the transplant length during operation of the aorta-coronary bypass]. AB - Determination of the necessary length of the bypass is one of the principal stages of operation of the aorta-coronary bypass. The greatest difficulty of the determination of the bypass length is the first-priority applying of proximal anastomoses. It requires the surgeon to have great experience, the operation to be longer. It also makes it necessary to prepare a conduit of deliberately excessive length. A device is proposed for the determination of the necessary bypass length during operation of aorta-coronary bypass consisting of a crocodile grip with a fixed to it polymer tube. PMID- 22774553 TI - [Method of plasty of defects of a hairy part of the head skin after tumor excision]. AB - Results of operative treatment of 8 patients with cellular basal cancer of the hairy part of the head are presented. The patients were operated by an original worked out method of plastic reconstruction of skin defects of the head hairy part after tumor excision. The mathematical substantiation of the surgical method was stated. The technique of operative intervention is described. The clinical course and illustration of the long-term results are given. PMID- 22774555 TI - [Application of a device for evacuation of fragments of biological tissue and uroliths in endoscopic operations]. AB - The proposed evacuator allows prevention of regurgitation of fragments of resected tissue of destructed bladder stones from the lower cavity of the device to the upper one, and then to the urinary bladder and, thus, it reduces loss of the biological material fragment for morphological investigation as well as the bladder stones fragments for an analysis of their chemical composition and structure, more effectively and quicklywash off the urinary bladder during endoscopic operations. PMID- 22774556 TI - [An experience with cardiac transplantation with a single stage reduction of the left atrium cavity and correction of valvular disease]. AB - The immediate and long-term results of cardiac transplantation with a reduction of the left atrium and correction of valvular diseases were performed on 4 patients with atriomegalia and associated valvular disease of the heart. There were no cases of hospital lethality. Within 7 days after operation the patients had a tendency to reducing the mean value of the left atrium. Within 38 months the tendency to normalization of the sizes, volumes and ejection fraction of the left atrium persisted. Cardiac autotransplantation is an effective method of a single stage reduction of the left atrium and correction of valvular diseases. PMID- 22774557 TI - [An experience with 100 cadaveric transplantations of the liver in the Russian Research Center of Radiology and Surgical Technologies]. AB - The authors made an analysis of their first 100 transplantations of cadaveric liver made at the period from 1998 through 2011. Postoperative complications and long-term results of transplantations at the period to 13 years are described. Cumulative survival up to 12 months was 91%, to 36 months--83%. Retransplantation of the liver was performed on 5 patients, 2 of them being successful. PMID- 22774558 TI - [Compliance predictors of patients with pulmonary tuberculosis needing phthisiological treatment]. AB - The factors predicting initial readiness of patients with infiltrative pulmonary tuberculosis to give their consent to transthoracic interventions were investigated. It was shown that initial readiness of patients to give their consent to phthisiological treatment directly depended on the indices of "social functioning" and lymphocyte percentage in leukogram. The total prognosis algorithm with 94.1% sensitivity and 75% specificity is presented as discriminative function estimated by "social functioning" data, lymphocyte percentage in leukogram and ordinal evaluation of complaints to sweating. PMID- 22774559 TI - [Minimally invasive operations for varicose disease of lower extremities]. AB - The authors discuss specific using minimally invasive surgical technique of ablation of the saphenous vein trunks by a modified Oesch PIN stripper method proposed by the authors. An experience with surgical treatment of 245 patients with varicose veins using the same modified technique is analyzed. Postoperative complications and medium-term results are evaluated. PMID- 22774563 TI - [Spontaneous combined incomplete transhepatic fistula of the gall bladder]. PMID- 22774560 TI - [Combined endovascular and surgical treatment of hemangioma of the tongue base]. PMID- 22774561 TI - [Giant chondrosarcoma of the anterior chest wall]. PMID- 22774562 TI - [Successful correction of biliary stricture after orthotopic transplantation of the liver]. PMID- 22774564 TI - [Use of delayed intestinal anastomosis in multisegmentary ulcer-necrotic lesion of the intestine in a newborn]. PMID- 22774565 TI - [Up-to-date approaches to prognozing and correction of intraoperative hemolysis in cardiosurgery]. PMID- 22774566 TI - [Tourniquet syndrome in children]. PMID- 22774567 TI - [Laboratory-based evaluation of "INOVA/QUANTA Lite" to determine antinuclear antibodies (ANA) and autoantibodies to double-stranded DNA, SS-A and SS-B]. AB - We evaluated QUANTA Lite reagent series (INOVA Diagnostics, CA, USA) to determine antinuclear antibodies (ANA) and autoantibodies to double-stranded (ds) DNA, SS-A and SS-B, in parallel with MESACUP (Medical & Biological Laboratories, Nagoya). Overall agreements between two reagents for qualitative interpretation ranged from 77.5% (ANA) to 99.0%(anti-SS-B antibodies). When we compared to the results by indirect fluorescent antibody (IFA) test on HEp-2 cells, QUANTA Lite ANA demonstrated better sensitivity and specificity; 92.2% versus 76.5% in sensitivity and 92.1% versus 86.8% in specificity. Also, determining anti chromatin antibodies and IFA test onto Chrithidia luciliae demonstrated greater interpretive correlation to detect anti-ds DNA by QUANTA Lite than by MESACUP. All the discrepant sera to which QUANTA Lite SS-A gave positive interpretations were confirmed to contain the antibodies specific to SS-A 52kDa antigen, which is supplemented to QUANTA Lite capture-probes. With these results, we can conclude that QUANTA Lite has superiorities over MESACUP; (1) to detect a variety of autoantibodies consisting of ANA, (2) to have a better correlation with confirmatory tests to detect anti-ds DNA antibodies, (3)to detect additional autoantibodies specific to SS-A 52kDa antigen, and (4) to have an enough compatibility in determining anti-SS-B antibodies. PMID- 22774568 TI - [Performance and clinical utility of a high-sensitivity troponin T assay]. AB - In the present study, we evaluated the performance and clinical utility of a high sensitivity troponin T (hs-cTnT) assay. The within- and between-assay variations (coefficients of variation: CV) in the low and high concentrations of troponin T in serum samples were 0.84% to 3.34%, respectively. Analysis of interferents showed that only hemoglobin negatively influenced the assay results. Blank assay was < 0.001 ng/mL, and a limit of quantification (10% CV) was found at 0.005 ng/mL. The correlation coefficient (r) between hs-cTnT and the conventional assay was 0.997 (p < 0.000). The high-sensitivity assay system could detect cTnT in 88% of samples in which the conventional assay could not detect any immunoreactivity. The 99th percentile in healthy subjects, determined using 559 samples from medical checkups, was 0.011 ng/mL. There was a gender difference (hs-cTnT levels were higher in men than in women), and hs-cTnT levels increased with age. Because hs-cTnT level exceeded 0.011 ng/mL approximately 2 hours after the onset of chest pain in patients with acute myocardial infarction, hs-cTnT can serve as a biomarker for early detection of myocardial infarction. There was a positive correlation (r = 0.491, p < 0.001) between hs-cTnT and NT-proBNP, and hs-cTnT levels increased with the progression of the disease state, as assessed using New York Heart Association (NYHA) classification. These findings indicate that the hs cTnT assay is sensitive enough to diagnose early-stage acute myocardial infarction and congestive heart failure. PMID- 22774569 TI - [Improvement in peripheral blood T cell subset imbalance in a house with an elimination system for various allergens]. AB - We analyzed the change of peripheral blood T cell subsets after moving into a house with a Healthy Air system (HAS) elimination system for various allergens, e.g. pollens, house dusts, etc. The 20 subjects were divided into an allergic group (13 subjects) and control group (7 subjects). We measured complete blood counts (CBC), white blood cell differentiation (DIFF), CD4/CD8 ratio, Th1/Th2 ratio, and percentage of CD4+CD25+T-cells and regulatory T-cells in peripheral blood, and these data were compared before and 3 and 6 months after moving into the HAS house. There was no significant difference in CBC, DIFF, CD4/CD8 ratio, and Th1/Th2 ratio before and after the move. The mean levels and 95% confidence interval of CD4+CD25+T-cells in the allergic group were as follows: before, 16.66% (12.99-20.34%); at 3 months, 13.86% (10.49-17.22%); and at 6 months, 12.66% (9.28-16.05%), respectively. Those in the control group were as follows: before, 13.60% (5.27-21.93%); at 3 months, 12.51%(5.41-19.61%); and at 6 months, 11.77% (3.93-19.61%), respectively. CD4+CD25+T-cells were significantly decreased at 6 months after the move compared to before the move in the allergic group (p < 0.01). However, there was no significant difference between before and after the move in the control group. The mean levels of regulatory T-cells were not different between before and after the move in both groups. The mean level of CD4+CD25+T-cells in subjects that had improved allergic condition was significantly decreased at 6 months after the move compared to before the move (p < 0.05). These results suggest that decreases in allergens in the home environment may affect lymphocyte subsets. PMID- 22774570 TI - [The performance of the automated immune chemiluminescent system "IMMULITE 2000XPi for the measurement of serum soluble IL-2 receptor in clinical samples]. AB - The performance of a chemical luminescence test reagent "Immulyze IL-2R II" with an automated immune chemiluminescent system "IMMULITE 2000XPi" for the measurement of serum soluble IL-2 receptor in clinical samples was investigated. The satisfactory results were obtained for the reproducibility, precision, linearity, and sensitivity, and no interference with hemolysis, bilirubin, chyle or intrafat was observed. A significant correlation was found between the values of sIL-2R measured by the Cell-free N IL-2R and those obtained by the IMMULYZE IL 2R II. The measurements were stable regardless of the methods of sample preservation, or repeated freeze-thawing procedures. Elevated concentrations of sIL-2R over 1,000 U/mL were found in multiple types of collagen diseases or severe cases of allergic diseases, indicative that sIL-2R levels might correlate with the severity of autoimmune diseases. In patients with lymphoma, sIL-2R levels correlated with the lactate dehydrogenase (LD) activity. Among the lymphoma cases with sIL-2R levels over 1,000 U/mL, the majority (84%) had significantly higher levels of LD, and among them, 81% were at the clinical stage IV. We observed that sIL-2R levels increased from the early stages of lymphoma, while LD activities increased at the advanced stages. Our present findings suggest that sIL-2R is a promising marker for the diagnosis of autoimmune and allergic diseases, and also for the diagnosis and staging of lymphomas. PMID- 22774571 TI - [Utility of rapid on-site cytology in endoscopic ultrasonography-guided fine needle aspiration of pancreatic masses]. AB - BACKGROUND: Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is a safe and effective method for obtaining samples for cytological diagnosis. Pancreatic cancer is extremely serious and often extremely aggressive, so early detection and diagnosis is important. Therefore, we actively perform EUS FNA for pathological diagnosis of cancer of digestive organs, especially the pancreas. MATERIALS AND METHODS: EUS-FNA was performed in 67 patients (39 male, 28 female, median age 63.3 years) from January 2007 to December 2010 in Kyoto University Hospital. To eliminate both quantitatively and qualitatively inadequate samples, we performed EUS-FNA with rapid on-site cytology. Two squash preparations of the collected cells from biopsy were retrieved. One was stained on-site with Giemsa for rapid cytology to evaluate the quantity and quality of the cell collection. If necessary, second or third trials were carried out to obtain appropriate samples for final cytology diagnosis. The other was wet-fixed and used for Papanicolaou staining. RESULTS: All 11 cases of inflammatory disease were diagnosed as negative on cytology. Solid-pseudopapillary neoplasm (1 case) and Endocrine neoplasms (3 cases) were correctly diagnosed on cytology. In pancreatic cancer, 49 of 52 cases (94%) were diagnosed as positive, but 3 cases (6%) were false-negative on cytology. The number of centesis for sampling was once in 21 cases, twice in 26 cases and more than twice in 20 cases. In this study of EUS FNA, sensitivity was 94% and specificity was 100%. CONCLUSION: Results of our examination suggest that the combination of EUS-FNA and rapid on-site cytology is a highly specific and sensitive test for detection of pancreatic cancer, and may contribute to reduce excessive centesis. PMID- 22774572 TI - [Construction and clinical evaluation of novel methods for detecting autoinomic dysfunction]. AB - The autonomic nervous system innervates every organ in the body. Since autonomic disturbances affect patient survival, an understanding of and recognition of these disturbances are important. We adopted several new methods to evaluate autonomic function accurately for detecting the onset of small-fiber neuropathy, such as laser-Doppler flowmetry, ultrasonography, 123I-MIBG scintigraphy, electrogastrography, cystometry, glucose-tolerance test, near-infrared spectrophotoscopy, blood pressure tests, and evaluation of sweating. After these examinations, we applied potential effective treatments to improve the survival and daily activity of these patients. We also evaluated the effect of liver transplantation on autonomic dysfunction of familial amyloidotic polyneuropathy (FAP) patients using our tools. Liver transplantation not only prevents the progression of autonomic dysfunction in these patients but also improves some autonomic symptoms in the early stage after the operation. As all domino-liver transplantation-induced amyloid neuropathies, including our cases, were of the sensory type rather than with autonomic involvement, assessment of the pain threshold by preferential stimulation of A delta fibers is a particularly useful tool for diagnosing the onset of small-fiber neuropathies in these patients in addition to autonomic testing. Analyses and comparison of patients with FAP and domino-liver-transplanted patients with autonomic, sensory and motor dysfunction may give a clue to elucidate the pathogenesis and treatment of neuropathy in FAP. As autonomic disturbances play an important role in the symptomatology of small fiber neuropathy, liver-transplanted FAP, and domino-liver-transplanted patients, further studies of autonomic dysfunction in these patients may lead to the pathogenesis of the disease. PMID- 22774573 TI - [Antibiotic-resistant bacteria and new directions of antimicrobial chemotherapy]. AB - The emergence and spread of antibiotic-resistant organisms are becoming more and more serious and are a worldwide problem. Recent trends in new antibiotic resistant organisms include multiple-drug resistant Pseudomonas aeruginosa (MDRP), MDR-Acinetobacter baumannii (MDR-AB) and New Deli metallo beta-lactamase 1 (NDM-1) -producing bacteria. Antibiotic combination therapy is an option to overcome these MDR organisms. A breakpoint checkerboard plate was created to measure antibiotic combination effects at breakpoint concentrations, making it possible to evaluate the synergy of antibiotic combination within 24 hours. In this article, recent topics regarding antibiotic-resistant organisms are briefly reviewed and the directions of antibiotic chemotherapy against these organisms are discussed. PMID- 22774574 TI - [Recognition of the importance of reversed CPC in CPC]. AB - Clinicopathological conferences (CPC) are one of the most important clinical conferences, and processes of both diagnosis and treatment performed in an autopsy case are retrospectively and finely checked to offer better medical treatment in the future. In CPC, the medical history, physical findings, laboratory data, image findings, diagnosis and treatment are discussed in the order that a physician examines a patient. Differential diagnoses usually decrease and several important diagnoses remain as the CPC discussion progresses. Medical treatment is also reexamined to identify a better approach. In this CPC, several medical doctors in various special fields try to understand the detailed state of the patient from each standpoint, and such a CPC is called an Expert CPC at Shinshu University School of Medicine. This CPC is carried out followed by reversed-CPC (R-CPC) of the same case. The purpose of this CPC is to understand the importance of R-CPC and to understand the correct interpretation of routine laboratory data. PMID- 22774575 TI - [Reversed clinicopathological conference (R-CPC)--interpreting laboratory data in the same way as physical findings]. AB - Routine laboratory data are discussed by time series analysis in reversed clinicopathological conferences (R-CPC) at Shinshu University School of Medicine. We can identify fine changes in the laboratory data and the importance of negative data (without any changes) using time series analysis. Routine laboratory tests can be performed repeatedly and relatively cheaply, and time series analysis can be performed. The examination process of routine laboratory data in the R-CPC is almost the same as the process of taking physical findings. Firstly, general findings are checked and then the state of each organ is examined. Although routine laboratory data are cheap, we can obtain much more information about a patient's state than from physical examinations. In this R CPC, several specialists in the various fields of laboratory medicine discussed the routine laboratory data of a patient, and we tried to understand the detailed state of the patient. R-CPC is an educational method to examine laboratory data and we, reconfirmed the usefulness of R-CPC to elucidate the clinical state of the patient. PMID- 22774576 TI - [Novel biomarker for pathological immature cells--soluble form of LR11]. AB - LR11 (also called SorLA or SORL1), a member of the LDL receptor family, was originally discovered in 1996 from genes specifically expressed in the intimal smooth muscle cells of atherosclerotic plaques. The soluble form of LR11 (sLR11) as well as the membrane-bound form plays a key role in the phenotype conversion of medial smooth muscle cells into intimal smooth muscle cells through the activation of urokinase receptor/integrin-mediated intracellular pathways. The levels of sLR11 in serum or CSF are increased in patients with atherosclerotic diseases, Alzheimer's disease or malignant diseases including acute leukemias. The recently developed ELISA system using two specific antibodies against LR11 made it possible to measure sLR11 quantitatively and stably for many samples. Thus, a novel clinical examination is expected to detect the pathological immature cells important for the pathophysiology of the above diseases. The soluble receptor-based clinical approach, together with basic studies about the structure-function relationship, may shed light on the development of novel target therapy against pathological immature cells in the science fields of so far independently categorized diseases. PMID- 22774577 TI - [Japan Surgical Society and Japanese Association of Anatomists: guidelines for cadaver dissection in education and research of clinical medicine]. PMID- 22774578 TI - [Japanese Association of Anatomists: a view on guidelines for cadaver dissection in education and research of clinical medicine]. PMID- 22774579 TI - [Self-introduction and my aspirations for anatomical education]. PMID- 22774580 TI - [Self-introduction of new professors (my profile and on hard tissue research)]. PMID- 22774581 TI - [Brain, mind and anatomy]. PMID- 22774582 TI - [Self-introduction and myambitions to the research]. PMID- 22774583 TI - [Inappropriate use of over-the-counter (OTC) drugs and their administration]. PMID- 22774584 TI - [Over-the-counter (OTC) drug poisoning in children and prevention strategies]. PMID- 22774585 TI - [Clinical presentation of over-the counter drug overdose]. PMID- 22774586 TI - [Administrative problem with OTC medications: a toxicologic perspective]. PMID- 22774587 TI - [Processing of hemolyzed blood with an ultrafiltration device for drug screening kits]. PMID- 22774588 TI - [Aggressive endoscopic removal of bezoars effective for the treatment of acute poisoning]. AB - A 37-year-old female presented with acute chlorpromazine and phenobarbital poisoning. Contrast enhanced abdominal CT on admission revealed a high density area at the gastric fundus and residual drugs were suspected. Activated charcoal and cathartics were administered following the gastric lavage under the intubation. As the plasma concentration of phenobarbital was high, urinary alkalinization and crystalloid infusion were carried out to reduce it. However, at 3 days after admission, the plasma concentration level had increased and the consciousness disturbance and respiratory depression continued. Abdominal CT was performed again and bezoars formation was suspected. Endoscopy was carried out to remove the bezoars. After the removal, the plasma concentration level significantly decreased. Her consciousness disturbance and respiratory depression also improved and high density area at the gastric fundus disappeared. Acute endoscopy is seldom advocated in cases of drug overdose. However, aggressive endoscopic removal should be considered in the case of acute poisoning of drugs with form bezoars. PMID- 22774589 TI - [Psychotropic drugs: Anxiolytics and hypnotics]. PMID- 22774591 TI - [News from the Japan Poison Information Center: 2011 annual report by JPIC]. PMID- 22774590 TI - [Accidental ingestion of chemical substances in the elderly]. PMID- 22774592 TI - [HLA and susceptibility to adverse drug reactions]. PMID- 22774593 TI - [Towards the elimination of onchocerciasis at the global scale: history, challenges and future prospects]. AB - The total number of patients with onchocerciasis on the African continent was estimated in 2008 at 25720000. The control strategy for onchocerciasis has dramatically changed during the last 30 years, resulting in a decrease of patients. Vector control was mainly used until around 1990. Since then, the strategy has been transferred to "Mass Drug Administration using Ivermectin". An "Integrated Approach" for several endemic diseases has become a popular control strategy since 2005. Several tasks remain for eliminating onchocerciais: improvement of the population coverage of drug distribution, construction of monitoring systems to inspect the emergence of drug resistance, invention of anti macrofilarial drugs to replace anti-microfilarial drugs, and reinforcement of the health authorities in African countries. The possible elimination of onchocerciasis also depends on the continued political commitment to the program by the Ministry of Health. If the ongoing control program keeps producing results at the current pace, the elimination of onchocerciasis could be achieved in the near future. PMID- 22774594 TI - [Causes of gelatinous material on ocular surface of a patient using timolol maleate long-acting eye drops]. AB - PURPOSE: To ascertain the causes of the formation of gelatinous material observed on the ocular surface of a patient using a betamethasone sodium phosphate ophthalmic solution containing fradiomycin sulfate (Rinderon-A) together with a timolol maleate long-acting ophthalmic gel-forming solution (Timoptol-XE). METHODS: The gellan gum in the Timoptol-XE was suspect as it might have been gelatinized by the fradiomycin sulfate in the Rinderon-A. Mixtures of the chemical compounds such as fradiomycin sulfate with the Timoptol-XE was tested in vitro to find out whether any resulted in gelation. RESULTS: It was confirmed that Timoptol-XE was gelatinized by the aminoglycoside drugs in vitro. The density of the aminoglycoside drugs needed for the gelation was only about 0.2 mM on average. Gelation was also observed with benzalkonium chloride and vancomycin. CONCLUSION: The results suggest that the gellan gum in the Timoptol-XE gelatinized by the fradiomycin sulfate in the Rinderon-A and that aminoglycocide compounds act strongly on gellan gum as polycation. PMID- 22774595 TI - [Long-term prognosis of 5 cases with stage 3A Coats disease after vitrectomy]. AB - PURPOSE: The effectiveness of laser photocoagulation and/or cryopexy to the abnormal retinal vessels for the treatment of eyes with Coats disease is reported. However, in Coats cases with serous detachment laser photocoagulation and/or cryopexy is sometimes not enough to coagulate and consecutively scar the abnormal vessels, leading to persistent subretinal fluid and multiple courses of treatment. Therefore, we investigated the long-term prognosis of Stage 3A Coats cases with macular detachment which underwent vitrectomy. METHODS: Five eyes of 5 cases (all men) with Stage 3A Coats disease, which underwent primary vitrectomy between 1999 and 2009, were investigated retrospectively. The average age at vitrectomy was 13.8 years (range; 6-21 years) and the average preoperative visual acuity in decimal equivalent was 0.1 (range; 0.04-0.5). The average follow-up period after vitrectomy was 83 months (range; 13-137 months). In the vitrectomy, posterior vitreous detachment either occurred or was confirmed. An intentional retinal hole was made and the subretinal fluid was drained through the hole. The abnormal vessels were coagulated by endo-diathermy and/or laser photocoagulation. The vitreous fluid was replaced with long-lasting gas or air. The visual acuity and the findings from the ocular fundus both before and after the vitrectomy were investigated. RESULTS: The average best-corrected visual acuities in decimal equivalent before, 3 and 12 months after the vitrectomy, and at the final visit were 0.1, 0.2, 0.2, 0.4, respectively. There was a statistically significant (p = 0.007) difference between the 4 time points, and the visual acuities at 12 months after vitrectomy and the final visit were significantly (p < 0.05) better than before the vitrectomy. The macular part of the retina in all 5 cases was attached once the gas in the vitreous cavity had disappeared. The foveal exudation which was observed before the vitrectomy in all 5 cases was completely absorbed after the vitrectomy. The average period from the vitrectomy to the complete absorption of the exudation was 20 months. Subfoveal fibrosis was observed in 4 of the 5 eyes and chorioretinal atrophy occurred in 3. CONCLUSIONS: Vitrectomy for eyes with Stage 3A Coats disease may be effective for visual prognosis compared to conventional therapy, i.e., laser photocoagulation and cryopexy, by enabling retinal attachment in the early postoperative period and by causing the foveal exudation to disappear. PMID- 22774596 TI - [Subthreshold micropulse diode laser photocoagulation combined with direct photocoagulation for diabetic macular edema in Japanese patients]. AB - PURPOSE: To investigate the efficacy of subthreshold micropulse diode laser photocoagulation (SMDLP) combined with direct photocoagulation. METHODS: Twenty one eyes of 20 patients with diabetic macular edema were treated with SMDLP and direct photocoagulation for microaneurysms within 1 month after SMDLP. The mean visual acuity in logMAR units and central macular thickness (CMT) were evaluated both before and after laser treatment by retrospective chart review and optical coherence tomography (OCT). RESULTS: The mean visual acuity did not change significantly at 3 and at 6 months. The mean CMT was significantly reduced at 3 and 6 months (3 months: p = 0.018, 6 months: p = 0.004). Visual acuity improved or maintained for 6 months in all of the patients (100%, 20 eyes of 20 patients). CONCLUSION: SMDLP combined with direct photocoagulation maintains visual acuity and improves diabetic macular edema for at least 6 months. PMID- 22774597 TI - [Analysis of retinal nerve fiber layer thickness in superior segmental optic hypoplasia (SSOH)]. AB - PURPOSE: To evaluate the clinical characteristics of patients with superior segmental optic hypoplasia (SSOH) and quantitatively assess the structural characteristics using optical coherence tomography (OCT). METHODS: Forty-three eyes of 43 subjects with SSOH and 30 eyes of 30 normal subjects as controls (mean age; 40.2 +/- 14.1, 42.9 +/- 9.9 years, mean refraction; - 4.6 +/- 3.7 D, -3.6 +/ 2.7 D, mean intraocular pressure; 14.6 +/- 2.5 mmHg, 14.3 +/- 3.2 mmHg, Humphrey visual field mean deviation; -4.31 +/- 4.3 dB, 0.01 +/- 1.2 dB) were enrolled. Forty-three eyes of the 43 patients with SSOH were examined by OCT for the quantitative assessment of the RNFL thickness (RNFLT). For the comparison of RNFLT, total average thickness, four quadrants and clock hour-based (12 equal 30 degree sectors) RNFLT were analyzed using OCT. RESULTS: OCT showed that the eyes with SSOH had significantly thinner RNFL than the normal subjects in total average thickness (SSOH 81.2 mm vs. 105.0 mm, p < 0.0001). Except for the temporal guadrant (p = 0.31), RNFL was thinner in superior, nasal(both p < 0.0001) and inferior (p = 0.002) guadrant. A comparison between the SSOH group and the normal control group for the 12 clock-hour segments in the OCT demonstrated that the patients with SSOH had decreased peripapillary RNFL thickness; the difference was statistically significant, except for the 7, 8, 9 and 10 o'clock segments. The area under the receiver operator characteristic curve (AUC) was greatest for the RNFL thickness of the 12 o'clock segment (AUC = 0.93), followed by the 1 o'clock segment (AUC = 0.90), and the 2 o'clock segment (AUC- = 0.87), as measured by the OCT. CONCLUSIONS: More generalized thinning of the RNFL and decreasing total average thickness except for the RNFL from 7 o'clock to 10 o'clock were identified in the eyes with SSOH with a relatively superior entrance of the central retinal artery and thinning of the superior retinal nerve fiber layer. It was also demonstrated that segments 12, 1 and 2 o'clock of the SSOH were highly useful for differential diagnosis. PMID- 22774598 TI - [HLA-class I gene polymorphisms in Japanese Stevens-Johnson syndrome patients with ocular surface complications]. AB - PURPOSE: Our previous study of polymorphisms in the HLA-class I genes of 71 Japanese SJS/TEN patients with ocular surface complications and 113 Japanese healthy controls showed that in the Japanese, HLA-A*0206 was strongly associated with SJS/ TEN. In this study, we examined 118 Japanese SJS/ TEN patients with ocular surface complications and a new control group consisting of 220 healthy Japanese volunteers, and investigated the association between HLA class I antigens, HLA-A, B, C, and the SJS/ TEN. METHODS: For HLA genotyping we enrolled 118 Japanese patients with SJS/TEN in the chronic or sub-acute phase at Kyoto Prefectural University of Medicine; all presented with ocular surface complications. We also enrolled 220 healthy Japanese volunteers. We performed polymerase chain reaction amplification followed by hybridization with sequence specific oligonucleotide probes (PCR-SSO). Results : HLA-A*0206 was most strongly associated with Japanese SJS/TEN patients with ocular surface complications (carrier frequency: p = 0.0000000002, OR = 5.2; gene frequency : p = 0.000000007, OR = 4.2). CONCLUSION: HLA-A* 0206 is strongly associated with Japanese SJS/TEN patients with ocular surface complications. PMID- 22774599 TI - [Establishment of a CMTM2 transgenic mouse model and the alteration of its serum testosterone level]. AB - OBJECTIVE: To establish a transgenic mouse model systemically expressing the CMTM2 gene and study the effect of the CMTM2 expression on the reproductive system of mice in vivo. METHODS: Transgenic mice were generated by microinjection of pRevTRE-CMTM2 and the genotype was detected by PCR. The expression of CMTM2 was determined by RT-PCR, Western blot and immunohistochemistry, and the serum testosterone level was measured by radioimmunoassay. RESULTS: The CMTM2 gene was highly expressed in the testis of the transgenic mouse models and in their offspring as well. The level of serum testosterone was significantly increased in the transgenic models as compared with the wild-type mice ([46.04 +/- 3.72] vs [42.43 +/- 3.80] nmol/L, P < 0.05). CONCLUSION: The transgenic mouse model was established successfully, which could highly express the CMTM2 gene. It is indicated that CMTM2 may influence steroidogenesis and testosterone secretion in transgenic mice. PMID- 22774600 TI - [Expression of iNOS in the testis of Fmr1 knockout mice in different developmental stages]. AB - OBJECTIVE: To analyze the expression of inducible nitric oxide synthase (iNOS) in the testis tissues of Fmr1 (fragile X mental retardation 1) knockout and wild type male mice in different developmental stages, and provide background information for researches on fragile X syndrome. METHODS: This study included 4, 6, 8 and 10 weeks old Fmr1 knockout and wild-type male mice, 6 in each age group. We identified the genotype of the mice by PCR, and detected and compared the expression of iNOS in the testis tissues of the Fmr1 knockout and wild-type mice by immunohistochemistry. RESULTS: The iNOS expression was weakly positive in the Leydig cells of the 4-week-old mice, moderately positive in the 6-week-old ones, and strongly positive in 8- and 10-week-old ones, significantly weaker in the Fmr1 knockout than in the wild-type ones. CONCLUSION: The expression of iNOS significantly decreases in the testis of Fmr1 knockout mice, suggesting that iNOS may be involved in the pathogenesis of fragile X syndrome. PMID- 22774601 TI - [Diagnostic value of MRI in testicular tumor]. AB - OBJECTIVE: To study the MRI manifestation of testicular tumor and the value of MRI in the diagnosis of the disease. METHODS: We retrospectively analyzed 23 cases of pathologically confirmed testicular tumor, and observed the morphological characteristics, signals and surrounding conditions of the tumor using plain and enhanced MRI scanning. RESULTS: Of the 23 cases, seminoma was identified in 7, mixed germinoma in 3, teratoma in 3, endodermal sinus tumor in 2, epidermoid in 1, Leydig cell tumor in 1, leucoma in 1, nonspecific inflammatory mass in 3, and tuberculosis in 2. MRI revealed the precise locations and specific characteristics of CONCLUSION: Based on MRI findings and clinical manifestation, most testicular tumors can be diagnosed correctly. PMID- 22774603 TI - [Establishment of an animal model of prostate cancer metastasis to the lung traced by AsRed2]. AB - OBJECTIVE: To establish an animal model of prostate cancer (PCa) metastasis to the lung using PCa PR7 (PCa PC-3 cells stably expressing red fluorescent protein AsRed2) cell lines that can be monitored by in vivo fluorescence imaging technology. METHODS: MTT and Transwell assay were used to compare the abilities of proliferation, migration and invasion of PC-3 and PR7 cells. Twenty BALB/c nude mice were equally randomized to 4 groups to receive tail vein injection of PR7 cell suspension at the concentration of 1 x 107/ml (group A), 2.5 x 107/ml (group B), 5 x 107/ml (group C) and 2.5 x 107/ml followed by the same dose 1 week later (group D). PCa metastasis to the lung was then monitored by in vivo fluorescence imaging technology at the end of 2, 4, 6 and 8 weeks. RESULTS: There were no statistically significant differences between PC-3 and PR7 cells in their abilities of proliferation, migration and invasion (P > 0.05). At the end of 4 weeks, lung metastasis was observed in 40% of the mice in group D, and at the end of 8 weeks, it was detected in 20% in group A, 60% in group B, 100% in group C, and 100% in group D, all confirmed by pathological examination. CONCLUSION: The animal model of PCa metastasis to the lung that can be monitored by in vivo fluorescence imaging technology was established successfully by tail vein injection of PR7 cells carrying red fluorescent protein. PMID- 22774602 TI - [Expressions of E-cadherin and alpha-catenin in benign, malignant and metastatic prostate tumors]. AB - OBJECTIVE: To investigate the expressions of E-cadherin (E-cd) and alpha-catenin (alpha-cat) proteins in benign and malignant prostate tumors, and determine whether they could be used as molecular markers for the prognosis of prostate cancer (PCa). METHODS: We detected the expressions of E-cd and alpha-cat in the prostatic tissues from 45 cases of PCa and 10 cases of benign prostatic hyperplasia (BPH) by immunohistochemical Elivision staining, and analyzed the relationships of E-cd and alpha-cat expressions with the PCa stage, PCa grade, preoperative PSA, results of endocrine therapy and prognosis. RESULTS: The E-cd protein was abnormally expressed in 86.7% of the PCa and 10.0% of the PSA patients, and the E-cd expression was significantly lower in the former than in the latter (P < 0.05). The abnormal expressions of E-cd in the PCa patients with metastasis, non-metastasis, Gleason score < or = 7 and > 7 were 85.0, 87.5, 100.0 and 86.7%, respectively, with no significant between-group differences (P > 0.05), those in the PCa patients with PSA < or = 10 and > 10 microg/L were 40.0 and 97.1%, respectively, significantly higher in the former than in the latter (P < 0.05), and those in the PCa patients with and without response to endocrine therapy were 93.8 and 72.7%, respectively, with no significant differences between the two groups (P > 0.05). The alpha-cat protein was abnormally expressed in 93.3% of the PCa and 30.0% of the BPH patients, respectively, and the alpha cat expression was significantly lower in the former than in the latter (P < 0.05). The abnormal alpha-cat expressions in the PCa patients with metastasis, non-metastasis, Gleason score > 7 and < or = 7 were 90.0, 100.0, 90.0 and 100.0%, respectively, with no significant between-group differences (P > 0.05), those in the PCa patients with PSA < or = 10 and > 10 microg/L were 40.0 and 94.3%, respectively, significantly higher in the former than in the latter (P < 0.05), and those in the PCa patients with and without response to endocrine therapy were 100.0 and 81.8%, respectively, with no significant differences between the two groups (P > 0.05). CONCLUSION: The expressions of E-cd and alpha-cat are significantly lower in PCa than in BPH, and they are not associated with cancerous metastasis, but negatively correlated with the PSA level in PCa patients. PMID- 22774604 TI - [Transrectal ultrasound-guided puncture and anhydrous alcohol sclerotherapy for Mullerian duct cyst]. AB - OBJECTIVE: To explore the effect of anhydrous alcohol sclerotherapy following transrectal ultrasound-guided puncture in the treatment of Mulllerian duct cyst. METHODS: Totally 44 patients with Mullerian duct cyst underwent transrectal ultrasound-guided puncture and sclerotherapy, 21 injected with anhydrous alcohol of half the volume of the aspirated cystic fluid followed by aspiration of all the fluid 5 minutes later (treatment group) , and the other 23 treated by cystic fluid aspiration only (control group). The clinical effects of the two methods were compared. RESULTS: The response rate and cure rate were 80.95 and 52.38% in the treatment group, as compared with 56.52 and 26.09% in the control (P < 0.001). No adverse events were observed in either of the two groups. CONCLUSION: Transrectal ultrasound-guided puncture and anhydrous alcohol sclerotherapy is a safe and effective approach to the treatment of Mulllerian duct cyst. PMID- 22774605 TI - [Expression of TEKT4 protein decreases in the ejaculated spermatozoa of idiopathic asthenozoospermic men]. AB - OBJECTIVE: To investigate the role of the TEKT4 protein in the pathogenesis of idiopathic asthenozoospermia. METHODS: We separated and purified the ejaculated sperm from idiopathic asthenozoospermia patients and normozoospermic men by Percoll discontinuous density gradients, and detected the distribution and the expressions of TEKT4 mRNA and TEKT4 protein by RT-PCR and Western blot. RESULTS: RT-PCR revealed that the expression of TEKT4 mRNA was significantly lower in the sperm of the idiopathic asthenozoospermia patients than in those of the normozoospermic men (0.59 +/- 0.13 vs 0.75 +/- 0.15, t = 4.325, P < 0.05), and Western blot confirmed the results of RT-PCR (0.48 +/- 0.14 vs 0.69 +/- 0.13, t = 5.939, P < 0.05). CONCLUSION: The expression of TEKT4 is significantly decreased in the ejaculated sperm of idiopathic asthenozoospermia patients, which might be one of the causes of idiopathic asthenozoospermia. PMID- 22774606 TI - [Microanatomy of blood vessels in spermatic cords and its clinical implication]. AB - OBJECTIVE: Both microsurgical subinguinal varicocelectomy (MSIV) and microsurgical high inguinal varicocelectomy (MHIV) are recommended for the treatment of varicocele, but they differ in technical complexity. This study aimed to determine the microanatomy of spermatic blood vessels in the two surgical approaches. METHODS: We recorded the numbers of spermatic veins, arteries and lymphatics in 80 cases of MSIV and 20 cases of MHIV. We also examined the spermatic cords from 10 adult male cadavers by histological staining. RESULTS: The numbers of medium spermatic veins (2 -5 mm in diameter) were 1.80 +/- 0.83 and 3.98 +/- 1. 99 in MHIV and MSIV, respectively, with significant difference between the two groups (t = -7.536, P < 0.01), and the total numbers of spermatic veins were 6.40 +/- 1.67 and 9.01 +/- 2.70, also with significant difference between the two (t = -4.071, P < 0.01). However, there were no significant differences between MHIV and MSIV in the numbers of small spermatic veins (diameter < or = 2 mm), large spermatic veins (diameter > or = 5 mm), arteries and lymphatics, nor in the numbers of spermatic veins and arteries of the cadavers. CONCLUSION: The total number of spermatic veins and the number of medium spermatic veins may be larger in MSIV than in MHIV, but the medium spermatic veins do not increase surgical difficulty, and MSIV is not more complicated than MHIV. PMID- 22774607 TI - [Pregnancy outcomes of day-2 versus day-3 embryo transfer in poor responders]. AB - OBJECTIVE: To investigate whether the day of embryo transfer (day 2 or day 3) affects clinical pregnancy outcomes in poor responder patients. METHODS: We retrospectively analyzed the pregnancy rates of 265 initial fresh cycles of in vitro fertilization-embryo transfer (IVF-ET), all transferred on day 2 (n = 169) or day 3 (n = 96) irrespective of quality because of an extremely low number of available embryos. RESULTS: Among the poor responders aged < 35 years, a higher rate of clinical pregnancy was achieved in the day-3 than in the day-2 group (50% vs 32.43% ; RR = 0.65, 95% CI: 0.43 - 0.99), and among those aged years, the two groups showed similar pregnancy outcomes. CONCLUSION: Shortening the time of embryo culture has no obvious benefit for the pregnancy outcome. For the poor responders under 35 years of age, day-3 embryo transfer may afford an even higher rate of clinical pregnancy. PMID- 22774608 TI - [Outcomes of IVF-ET and percentage of morphologically normal sperm before and after swim-up treatment]. AB - OBJECTIVE: To study the relationship between sperm morphology and the outcomes of in vitro fertilization-embryo transfer (IVF-ET) before and after swim-up treatment of sperm on the day of oocyte retrieval. METHODS: This study included 94 couples to be treated by IVF-ET for tubal factor infertility. Sperm samples were collected on the day of oocyte retrieval and sperm morphology evaluated according to the Kruger criteria before and after swim-up treatment. Based on the results of morphological evaluation, the sperm samples were divided into groups A1 (morphologically normal sperm > or = 10% after swim-up treatment), A2 (morphologically normal sperm < 10% after swim-up treatment), B1 (morphologically normal sperm > or = 10% before swim-up treatment) and B2 (morphologically normal sperm < 10% before swim-up treatment). The outcomes of IVF-ET treatment were compared between groups A1 and A2 as well as between B1 and B2. RESULTS: After swim-up treatment, the rates of fertilization, cleavage, good quality embryo, clinical pregnancy and embryo implantation of group A1 were (72.72 +/- 3.35)%, (95.64 +/- 2.04)%, (24.39 +/- 4.57)%, 50.00% and 23.87%, respectively, while those of group A2 were (70.27 +/- 8.82)%, (94.82 +/- 4.94)%, (13.45 +/- 7.39)%, 9.52% and 6.25%, respectively, the latter three indexes remarkably higher in A1 than in A2 (P < 0.05), but the differences in the former two not statistically significant (P > 0.05). Before swim-up treatment, the above five indexes were (72.90 +/- 4.23)%, (95.20 +/- 2.61)%, (23.35 +/- 5.19)%, 39.58% and 18.35% in group B1, as compared with (71.33 +/- 5.10)%, (95.71 +/- 2.88)%, (20.18 +/- 6.15)%, 41.86% and 21.28% in group B2, with no statistically significant differences between the two groups (P > 0.05). CONCLUSION: The percentage of morphologically normal sperm after swim-up treatment on the day of oocyte retrieval may be a valuable predictor of the outcomes of IVF-ET. PMID- 22774609 TI - [Vitrification of oocytes for in vitro fertilization and embryo transfer]. AB - OBJECTIVE: To explore the feasibility, indication and method of oocyte vitrification during the IVF - ET procedure, so as to increase the utilization of oocytes and reduce oocyte waste. METHODS: This study included the patients whose husbands failed to provide sperm samples at the time of oocyte pickup or from whom more than 25 oocytes were obtained. With the patients' consent, some of their oocytes were subjected to cryopreservation by vitrification, and used for IVF - ET after thawed. RESULTS: Totally, 53 oocytes from 7 patients were thawed, and 44 (83.02%) survived, of which 41 M II oocytes were subjected to ICSI and 32 (72.73%) were fertilized. Thirty embryos were formed, with a cleavage rate of 93.75%. Sixteen embryos were transferred in 9 cycles, with achievement of 2 clinical pregnancies and delivery of 3 healthy babies. The implantation rate was 18.75% and the live birth rate 22.22%. Seven of the embryos were still cryopreserved. CONCLUSION: Cryopreservation of oocytes by vitrification effects satisfactory rates of survival and fertilization, and that of surplus oocytes can increase oocyte utilization and adds to the alternatives for IVF - ET. PMID- 22774610 TI - [IFN-gamma enzyme-linked immunospot assay versus PPD tuberculin skin test in the diagnosis of tuberculous epididymitis]. AB - OBJECTIVE: To explore the potential application of IFN-gamma enzyme-linked immunospot (ELISPOT) assay in the diagnosis of tuberculous epididymitis (TE) by comparing ELISPOT assay with the traditional purified protein derivative (PPD) tuberculin skin test. METHODS: We examined 13 TE patients using an in-house ELISPOT kit, another 11 TE patients by PPD skin testing, and 57 healthy male volunteers by parallel test with both the methods. RESULTS: Twelve (92.3%) of the 13 TE cases were positive on ELISPOT assay, and 10 (90.9%) of the 11 TE cases positive on PPD skin test, with no statistically significant differences between the two groups (P > 0.05). Among the 57 healthy male volunteers, 8 (14.0%) were positive on ELISPOT, and 28 (49.1%) positive on PPD test, the latter significantly higher than the former (P < 0.001). CONCLUSION: In terms of sensitivity, ELISPOT assay is similar to PPD test in the examination of tuberculous epididymitis. As for specificity, ELISPOT assay seems better than PPD test in differentiating tuberculous epididymitis patients from healthy males. PMID- 22774611 TI - [Half-gloving cordectomy: a modified procedure for concealed penis]. AB - OBJECTIVE: To search for a simple surgical procedure for the treatment of concealed penis that may have better effect and less complications. METHODS: We used a modified surgical method in the treatment of 58 patients with concealed penis aged from 3 to 15 (mean 6.8) years. The operation was simplified and involved the following steps: wholly unveiling the penis glans, half-degloving the foreskins, cutting off all the adhesive fibers up to the penile suspensory ligaments, and liberating the external penis. RESULTS: The operation was successful in all the patients, with the operative time of 15 -45 (mean 33) minutes, hospital stay of 2 - 5 (mean 3.5) days, but no complications except mild foreskin edema in 5 cases. The external penis was prolonged from 0.5 - 2.8 (mean 1.4) cm preoperatively to 3.2 - 8.5 (mean 3.9) cm postoperatively. The patients were followed up for 1 -3 years, all satisfied with the length and appearance of the penis, and their sexual and reproductive functions were normal. CONCLUSION: The modified surgical procedure for concealed penis is simple and effective, with desirable outcomes, few postoperative complications and no damage to sexual and reproductive functions. PMID- 22774612 TI - [Radioiodine-131 therapy improves sex hormones and sexual function in male patients with Graves' disease]. AB - OBJECTIVE: To observe the changes of sex hormones and sexual function in male patients with Graves' disease (GD) after Radioiodine-131 (I-131) therapy. METHODS: Thirty-four male GD patients, aged 21 -40 (32.3 +/- 6.7) years, were treated with I-131 at the dose of 111 - 407 (237.8 +/- 51.8) MBq. The levels of serum sex hormones were measured, and the patients'scores on erectile function (IIEF-5) were obtained before and 3 and 6 months after the treatment. Another 20 healthy men aged 25 - 37 (31 +/- 3.1) years were enlisted as controls. RESULTS: The baseline levels of estrogen (E2), testosterone (T) and luteinizing hormone (LH) were (132.5 +/- 40.4) pmol/L, (21.6 +/- 4.6) nmol/L and (10.1 +/- 4.4) IU/L in the GD patients, significantly higher than (80.4 +/- 31.2) pmol/L, (14.5 +/- 4.2) nmol/L and (6.2 +/- 1.9) IU/L in the healthy controls (P < 0.05). The E2, T and LH levels showed a significant decrease in the GD patients after 3 months of treatment ([110.2 +/- 20.6] pmol/L, [17.7 +/- 5.5] nmol/L and (9.4 +/- 3.9) IU/L, P < 0.05), but exhibited no statistically significant differences from the healthy controls at 6 months ([82.6 +/- 30.1] pmol/L, [13.8 +/- 3.4 ] nmol/L and [6.6 +/- 1.5] IU/L, P > 0.05). The IIEF-5 score of the GD patients was 5 - 25 (15.5 +/- 3.5) before I-131 treatment, significantly lower than that of the controls (19 - 25, 24 +/- 0.5) (P < 0.05), and it was 8 - 25 (19.5 +/- 1.0) at 3 months and 10 - 25 (23.5 +/- 1.5) at 6 months, significantly higher in the latter than in the former (P < 0.05), and with no significant difference between the 6 month treated patients and the healthy controls (P > 0.05). CONCLUSION: The E2, T and LH levels are increased while the IIEF-5 score decreased markedly in male GD patients. Six-month treatment with I-131 can not only restore the E2, T and LH levels to normal but also significantly improve the patient's sexual function. PMID- 22774613 TI - [Cytogenetics and Y chromosome AZF microdeletions in infertile patients with mosaic karyotype Klinefelter syndrome (46,XY/47,XXY/48, XXYY/49,XXXXY)]. AB - OBJECTIVE: To observe peripheral blood chromosome abnormality and microdeletions of the SRY and AZF genes on the Y chromosome in patients with chimera Klinefelter syndrome. METHODS: We analyzed the cytogenetic karyotype of the peripheral blood chromosome in 1 infertile patient with mosaic karyotype Klinefelter syndrome and his parents. We identified 9 sequence tagged sites (STS) by multiplex PCR: sY84, sY86, sY127, sY129, sY134, sY254, sY255, sY242, and sY152. Meanwhile we detected the SRYgene and the microdeletion of AZF using ZFX/ZFY as the internal control gene. RESULTS: The karyotype of the patient was 46,XY (12%)/47,XXY (30%)/48,XXYY (56%)/49,XXXXY (2%). The karyotypes of his parents were normal. Consistency was found between the SRY gene and the chromosome gender in the patient and his parents. Y chromosome AZF microdeletion was observed in the patient. The deletion sites were sY86 and sY127, and the deletion type was AZFa + AZFb. CONCLUSION: AZF microdeletion of the Y chromosome exists in patients with Klinefelter syndrome. Chromosome karyotype and Y-chromosome AZF microdeletion are important criteria for the genetic diagnosis of Klinefelter syndrome. PMID- 22774614 TI - [Microdissection testicular sperm extraction for non-obstructive azoospermia]. AB - Patients with non-obstructive azoospermia was once considered to be infertile due to impaired testicular spermatogenesis and consequent absence of sperm in the ejaculate. With the advent of intracytoplasmic sperm injection (ICSI), various testicular sperm retrieval techniques have been introduced recently, including fine needle aspiration, testicular sperm extraction, microdissection testicular sperm extraction, and so on. A large number of studies show that sperm can be retrieved in non-obstructive azoospermia patients, even in those with Klinefelter syndrome, because of the existence of isolated regions of spermatogenic tissue within the testis. 2010 EAU guidelines on male infertility recommend testicular sperm extraction or microdissection testicular sperm extraction for sperm retrieval from non-obstructive azoospermia. However, compared with testicular sperm extraction, the latter has a higher sperm retrieval rate with minimal postoperative complications. This article presents an overview on the prediction, operative procedure, sperm retrieval rate and postoperative complications of microdissection testicular sperm extraction. PMID- 22774615 TI - [Shengjing tablets for semen non-liquefaction: a clinical study of 100 cases]. AB - OBJECTIVE: To investigate the efficacy and action mechanism of Shengjing Tablets in the treatment liquefaction. METHODS: We randomly assigned 150 patients with semen non-liquefaction to receive Shengjing Tablets group, n = 100) and vitamin E capsules (control group, n = 50) for 2 courses of 45 days each, followed by observation liquefaction time and other semen parameters. RESULTS: After the first course, 68 of the patients in the treatment group 20 responded and 12 failed to respond; and after the second course, 84 were cured, 9 responded and 7 failed to respond, effective rate of 93.0%. In comparison, only 8 of the controls were cured, 8 responded and 34 failed to respond after medication. There were statistically significant differences between the two groups (P < 0.01). Meanwhile, the treatment showed obvious improvement in sperm motility and concentration. CONCLUSION: Shengjing Tablets may shorten the time liquefaction, and can be used as a safe and effective therapy for semen non-liquefaction. PMID- 22774616 TI - Validity evaluation of in-house preparation kit, vaginal pH paper test combined amine tube test, for the simple diagnosis of bacterial vaginosis. AB - OBJECTIVE: Determine the positive in-house preparation kit for suggested bacterial vaginosis (BV) for both elevated vaginal pH > 4.5 and positive amine test, as well as evaluate for validity of sensitivity, specificity, positive predictive value, and negative predictive value against Chandeying criteria for confirmed BV. MATERIAL AND METHOD: A cross-sectional study among the women who presented with an abnormal vaginal discharge (AVD) or asymptomatic annual cervical cytology screening was done. Each vaginal discharge was divided into two parts of investigation. The first part included the clinical criteria of confirmed BV, based on at least three out of five indicators, the vaginal pH > 4.5, homogeneous and thin discharge (milky discharge), positive sniff/amine test, clue cell > 20% of total vaginal epithelial cells, and scanty or absence lactobacilli. The second part included the in-house preparation kit of suggestive BV relied on elevated vaginal pH > 4.5 and positive amine tube test. RESULTS: Twenty-six women were enrolled. Of the complaint of AVD/asymptomatic had 2/10 of confirmed BV (12 cases), and 1/13 of confirmed non-BV (14 cases). The in-house preparation kit, compared with the clinical criteria, had sensitivity of 91%, specificity of 71%, positive predictive value of 73%, and negative predictive value of 90%. There were false negative of 1/12 cases (8.3%), and false positive of 4/14 cases (28.5%). CONCLUSION: The in-house preparation kit favorably compared with the clinical criteria and has the advantage of being simple, rapid, and easily performed in resource poor setting. Further development on sensitivity and specificity of the test is suggested. PMID- 22774617 TI - Cuff leak volume as a clinical predictor for identifying post-extubation stridor. AB - BACKGROUND: Post-extubation stridor occurs after translaryngeal intubation results to re-intubation in a number of patients. OBJECTIVE: To determine the cut off value of the cuff leak volume test among Thai patients as a predictor for post-extubation stridor MATERIAL AND METHOD: Demographic data and cuff leak volume were collected from patients who had been intubated with planned extubation. Clinical stridor was observed and identified after extubation. RESULTS: Among 115 patients, the cuff leak volume of less than 114 ml was used to predict post-extubation stridor with the sensitivity of 89%, specificity of 90%, positive predictive value of 65%, and negative predictive value of 98%, respectively. Among the stridor group, 12 of 19 cases (63.2%) needed re intubation. CONCLUSION: The cuff leak volume of less than 114 ml can be used as a clinical predictor for identifying post-extubation stridor PMID- 22774618 TI - Outcome of neonates exposed to active pulmonary tuberculosis. AB - OBJECTIVE: To determine the incidence of tuberculosis infection and disease in neonates exposed to an active pulmonary tuberculosis patient in a nursery and maternity ward. MATERIAL AND METHOD: Descriptive cohort study was carried out in Srinagarind Hospital, Khon Kaen University, North-East Thailand. A smear positive pulmonary tuberculosis mother with productive cough was diagnosed on the fifth day of admission. The authors urged parents of all exposed neonates to accept isoniazid (INH) prophylaxis for their infants for six months. All neonates underwent chest x ray (AP, lateral view) and tuberculin skin test on the 24 months follow-up. RESULTS: The 48 neonates were identified as exposed. The age of follow-up ranged from 30 to 32 months. Only three were lost to follow-up. Of the remaining 45 neonates, six refused to take INH prophylaxis. Complete six months of LNH prophylaxis were observed in 27 (60%) of 39 contacts. Tuberculin skin tests (TST) were performed in all of 45 contacts. No cases were positive for TST. Abnormal chest radiographies were found in nine of INH group, three patients had hilar lymphadenopathy and six had pneumonia. The repeat chest x ray, two weeks later was normal in all cases. After 30 to 32 months follow-up, none of the 39 neonates who received INH prophylaxis or the six neonates progressed to have active tuberculosis. CONCLUSION: In exposed neonate identified as the high-risk group, appropriate INH prophylaxis, and long-term follow-up, especially in the first-2 years, seemed to be effective in preventing the development of active tuberculosis. PMID- 22774620 TI - Single-incision versus conventional multiple-incision laparoscopic cholecystectomy at Hat Yai Hospital. AB - OBJECTIVE: To compare single-incision laparoscopic cholecystectomy (SILC) with conventional multiple-incision laparoscopic cholecystectomy (CMILC). MATERIAL AND METHOD: The data were retrospectively collected for patients undergoing SILC, and CMILC at Hat Yai Hospital between September 2009 and October 2011. The operative time, hospital stay, postoperative pain, number of narcotic doses, conversion to open surgery, and postoperative complication were analyzed. RESULTS: Of SILC/CMILC groups, 107/108 subjects, the mean operative time was 81.1/74.4 minutes, and SILC was statistically longer (p < 0.001). Among SILC/CMILC group, 9/0 cases required the extra ports, as well as 2/5 cases of conversion to open surgery. The mean length of stay of SILC/CMILC was statistically longer of 4.6/3.7 days (p = 0.04), in contrast with the mean postoperative pain at 8 hours was statistically lower of 3.4/4.2 (p = 0.03). Both groups, the postoperative complication had similar proportion. CONCLUSION: Preliminary results of the present study showed SILC to be safe compared with CMILC, although operative times were longer. PMID- 22774619 TI - Postoperative fever and major infections after pediatric cardiac surgery. AB - OBJECTIVE: 1) to identify the current status of major infections and other etiologies of postoperative fever from pediatric cardiac surgery 2) to determine the risk factors of major infections. MATERIAL AND METHOD: Databases of pediatric cardiac surgery patients in 2005 were retrospectively reviewed. The main outcomes of interest were postoperative fever and its etiologies. Potential predictors were analyzed by comparing patients who developed or did not have infections. RESULTS: Two hundred thirty patients, 43% (n = 99) developed postoperative fever. Major infections occurred in 13.5% (n = 31), and postpericardiotomy syndrome (PPS) was seen in 8.7% (n = 20) of the patients. The infection rate was 16.9/100 procedures, including pneumonia (29 episodes) and bloodstream infection (6 episodes). Risk factors were infancy, prolonged ventilator support > 2 days, hospital length of stay (LOS) > 14 days, intensive care unit (ICU) LOS > 3 days, re-open procedure, and extubation failure rate. Conversely, cyanosis and high complexity operations were not associated. Positive erythrocyte sedimentation rate was related to infections or to PPS (the area under the ROC = 0.72). CONCLUSION: Following pediatric cardiac surgery major infections are still problematic. The risks increase with infancy, prolonged ventilator support, prolonged hospital and ICU LOS, re-open procedure, and extubation failure. PMID- 22774621 TI - Skin sparing mastectomy with immediate reconstruction in early breast carcinoma: a preliminary study. AB - BACKGROUND AND OBJECTIVE: Surgical treatment for breast cancer has some special aspects different from other cancers, since surgeons have to concern of both oncologic safety and esthetic outcome. Modified radical mastectomy (MRM) can give the oncologic safety but not esthetic outcome. Breast conserving therapy improves cosmetic but results in more local recurrence than modified radical mastectomy. Skin sparing mastectomy (SSM) with immediate reconstruction for early breast cancer has been reported by several investigators to have comparable outcome with MRM and better esthetic result. The purpose of the present study was to examine patients who underwent SSM with immediate reconstruction at King Chulalongkorn Memorial Hospital. MATERIAL AND METHOD: Patients who underwent SSM with immediate reconstruction by the authors at King Chulalongkorn Memorial Hospital, Bangkok Thailand between May 2007 and January 2011 were studied. The immediate reconstruction was performed with transverse rectus abdominis musculocutaneous flaps or latissimus dorsi flaps. Postoperative early and late complications as well as local recurrence were studied to examine the oncologic safety and esthetic outcome. RESULTS: Fourteen patients were enrolled into the present study. The age ranged from 33 to 59 years (mean 47 years). The follow up time ranged from six to 50 months (mean 26.5 months). Postoperative complications included wound infection in one patient (7%), seroma at donor site of latissimus dorsi flaps in two patients (40%) and fat necrosis in five patients (55%). There was no skin flap necrosis, no hematoma, no arm numbness, no wound dehiscense, no abdominal wall hernia, and no lymphedema of the arm. No local recurrence was detected CONCLUSION: This preliminary report shows that skin-sparing mastectomy with immediate reconstruction is a good alternative in management of early breast cancer. There was no serious postoperative complication. The esthetic result was acceptable. No local recurrence was observed. Long-term follow up with more patients are required to confirm its applicability in early breast cancer patients. PMID- 22774622 TI - Surgical outcome of the non-shunt carotid endarterectomy. AB - BACKGROUND AND OBJECTIVE: Nearly 60 years after the advent of carotid endarterectomy (CEA), controversy continues regarding the necessity of an indwelling shunt during carotid reconstruction. Reasonable arguments have been made for monitoring-dependent shunting, and remarks can be made in favor of non shunt procedure. Based on the results of several studies, most strokes after CEA are thromboembolic and result from technical failures e.g. residual plaque fragments, and stenosis during arterial repair. The objective of the present study is to present the details and results of CEA without an intraluminal shunt. MATERIAL AND METHOD: A retrospective study was performed to determine the efficacy of non-shunt CEA. During a four-year period, 25 patients, ranging from 49 to 81 years underwent 25 consecutive CEA. RESULTS: The clinical presentations were previous minor stroke in 12, reversible ischemic neurological deficit in eight, and TIA in five. There was no early post-operative mortality. Neither carotid clamp time nor the presence of contralateral disease correlated with the occurrence of post-operative stroke. CONCLUSION: Although the authors' experience may be limited in terms of numbers of patients, satisfactory results in carotid reconstruction could be obtained using safe performance of CEA without intraluminal shunt. PMID- 22774623 TI - Femoral head-neck diameter and ratio in Thais: a cadaveric study. AB - OBJECTIVE: To report the femoral head and neck diameter in both coronal and sagittal planes, the femoral head-neck ratio, and the difference between sex in a normal Thai population. MATERIAL AND METHOD: One hundred two femoral bones without visible previous disease or deformity of the head, neck, and shaft that included 50 male donors and 52 female donors, with an average age of 58.8 years (range 25 to 85) were included in the present study. The measurement of the femoral head and neck diameters was performed by using Vernier calipers (scale 150 x 0.02 mm). RESULTS: The mean head and neck diameters in coronal and sagittal planes in male and female are 45.25, 45.23, 40.28, 40.13 mms (p = 0.000), and 30.80, 25.65, 27.79, 22.08 mms (p = 0.000), respectively. The head-neck ratio in each plane in both male and female are 1.47, 1.45 (p = 0.257), and 1.77, 1.83 (p = 0.016), respectively. CONCLUSION: The very small average diameter of femoral head, especially in Thai females, should warn surgeons to carefully consider and then, perform hip resurfacing arthroplasty to avoid early complication from neck notching and mal-position. The head-neck ratio of the present study group is high enough to anticipate that postoperative anterior impingement of the neck and acetabulum or limiting hip flexion is unlikely to occur. PMID- 22774624 TI - Clinical characteristics of Thai patients with psoriasis. AB - OBJECTIVE: To reveal the clinical manifestations, aggravating factors, factor associated with severity, and treatment of psoriasis in Thai patients. MATERIAL AND METHOD: The data of psoriasis patients who had been visited Dermatologic outpatient clinic, Siriraj Hospital between July 2002 and July 2008 were retrospectively reviewed. RESULTS: One thousand eighty two patients were studied. The male to female ratio was 1.2:1 and the peak age of onset was in the 40 to 49 year-old age group. The most common aggravating factor was stress (50%), followed by trauma (39%) and weather condition (35%). The majority of patients had plaque type (72.8%). Male gender, smoking, alcohol intake, and nail abnormalities were related to severe psoriasis (PASI > 10). CONCLUSION: The present study demonstrated the demographic data of Thai psoriasis patients in a large number of population. These data would be beneficial for national public health development of Thailand in order to provide the better care for Thai psoriasis patients. PMID- 22774625 TI - Comparison between the radiographic findings in pulmonary tuberculosis of children with or without HIV infection. AB - OBJECTIVE: Identify the difference between radiographic findings in children with pulmonary tuberculosis with and without HIV infection. MATERIAL AND METHOD: The authors retrospectively reviewed the chest radiography of 93 children (under 15 years of age) with pulmonary tuberculosis between January 2000 and June 2005. Fifty-two of the children had an HIV co-infection while the remaining 41 children did not. The chest radiographic findings were assessed for parenchymal changes, lymphadenopathy, and pleural effusion. RESULTS: The radiographic manifestations in the HIV-infected group included interstitial infiltration in 39 patients (75%), alveolar infiltration in five patients (9.6%), combined interstitial and alveolar infiltration in seven patients (13.4%), miliary infiltration in one patient (1.9%), and hilar/mediastinal lymphadenopathy in 17 patients (32.6%). One patient had extensive alveolar infiltration in conjunction with multiple cavitatary formations. The findings in the non-HIV-infected group were interstitial infiltration in 30 patients (73.1%), hilar/mediastinal lymphadenopathy in 13 patients (31.7%, 3 of whom had adenopathy without parenchymal infiltration), and pleural effusion in two patients (4.8%). Other less frequent abnormalities included bronchiectasis, peribronchial thickening in the HIV-infected group, and atelectasis and granuloma in the non-HIV-infected group. There was no statistically significant difference in the radiographic findings between the two groups, except the association of hilar/mediastinal lymphadenopathy and pulmonary infiltration. Regarding hilar/mediastinal lymphadenopathy with or without pulmonary infiltration between the two groups, all cases in the HIV-infected group with hilar/mediastinal lymphadenopathy were significantly more associated with pulmonary infiltration (17 patients) than the other group (8 patients) (p = 0.009). CONCLUSION: Hilar/mediastinal lymphadenopathy with pulmonary infiltration strongly suggests the presence of HIV infection in children with pulmonary tuberculosis. PMID- 22774626 TI - Accuracy and precision evaluation of Thai plastic microhematocrit tubes: the first product from Thailand. AB - BACKGROUND: In Thailand, the spun microhematocrit method is usually performed using glass microhematocrit tubes even though broken glass tube during use may result in a risk of injury and blood-borne infection. The main reason is that the safer product alternatives such as plastic microhematocrit tubes are more expensive. Now, plastic tubes for hematocrit determination can be produced in Thailand at a much cheaper price. However precision and accuracy studies are necessary before being able to use them. OBJECTIVE: To compare the accuracy and precision of Thai plastic microhematocrit tubes against the routinely used glass microhematocrit tubes and imported plastic microhematocrit tubes using spun microhematocrit method. MATERIALS AND METHOD: One hundred residual EDTA blood samples from the Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand along with the three level hematology control materials were measured with spun microhematocrit values using three different types of plastic microhematocrit tubes. This was compared to the routinely used glass microhematocrit tubes as a gold standard. RESULTS: The repeated measures one-way ANOVA found no significant difference between the hematocrit values from each type of tubes with an F(1,99) = 0.667 and p-value = 0.574. Intraclass correlation coefficient (ICC) between four types of microhematocrit tubes ranged from 0.996-0.998 (p-value < 0.001). Correlation coefficients (r) between four types of microhematocrit tubes ranged from 0.996 0.998 (p-value < 0.05). Coefficient of variation (CV) for precision of both within run and between run of Thai plastic microhematocrit tubes ranged from 1.44 to 2.17% compared to 1.39 to 4.01% of the imported plastic microhematocrit tubes. CONCLUSION: The hematocrit values determined by all plastic microhematocrit tubes can be considered relatively equivalent to those of glass microhematocrit tubes in terms of accuracy and precision. The Thai plastic microhematocrit tubes are economical and with the cost-benefit over other plastic tubes of about 12 to 16 times. Therefore, the Thai plastic microhematocrit tubes should be the choice for glass tube replacement. PMID- 22774627 TI - Androgen-producing adrenocortical carcinoma: report of 3 cases with different clinical presentations. AB - Adrenocortical carcinoma is extremely rare in children. The majority of cases presented with a combination of clinical features of Cushing syndrome and hyperandrogenism. The authors report three cases of isolated androgen-producing adrenocortical carcinoma with different clinical presentations. The two cases had clinical manifestations of hyperandrogenism: one boy with isosexual pseudoprecocity and one girl with heterosexual pseudoprecocity, both of whom underwent complete tumor removal and were well after surgery. The third patient presented with a huge abdominal mass and weight loss. Local and distant metastases (both lungs) were detected at the time of diagnosis. The patient expired after 36 days of hospitalization. The pathological section in all three patients demonstrated highly pleomorphism, increased mitoses, and scattered areas of necrosis. All cases had high levels of 1 7-hydroxyprogesterone, dehydroepiandrosterone-sulphate, and testosterone. PMID- 22774628 TI - Pediatric fatality from gun bluing solution: the need for a chemical equivalent of the one-pill-can-kill list. AB - Gun bluing solution is commonly used to polish guns and prevent rusting. The authors report a case of a 2-year-old boy who inadvertently ingested approximately 15 ml of his father's Fox Gun Blue solution. The patient subsequently developed acidosis, hypotension, and coma. He died within four hours after ingestion. His plasma selenium level was 857 ng/ml. A brief review of other reported ingestion of gun bluing liquid in both adults and children is also included. PMID- 22774629 TI - Three-day unrecognized cefazolin anaphylaxis in a case undergoing coronary bypass graft surgery. AB - Cephalosporin anaphylaxis is rare but the diagnosis is usually not delayed when the catastrophic reaction occurs shortly after cephalosporin injection. The authors wish to report a patient who had never had a history of beta-lactam hypersensitivity and developed the first episode of cefazolin anaphylaxis during coronary artery bypass surgery. Hypotension developed during the operation but it was immediately corrected by volume infusion and inotrope administration. Shaking chills, drenching sweats, and tingling sensation on the head developed when she regained consciousness from general anesthesia. The adverse reaction disappeared soon and was thought to be the side effects of anesthetic drugs, morphine administrations, and/or blood transfusion. Similar reactions, together with hypotension and oxygen desaturation, recurred each time cefazolin was infused but it took three days and doses of 12 grams of cefazolin administration before a correct diagnosis was reached. The present case report would remind surgeons and anesthesiologists of cefazolin as a potential cause of anaphylaxis during peri- and post-operative periods. PMID- 22774630 TI - Endogenous Klebsiella panophthalmitis: atypical presentation. AB - Endogenous endophthalmitis caused by K. pneumoniae was considered to be a rare cause of endogenous endophthalmitis. Most of the patients had prior medical conditions, and diabetes is the most common underlying condition. Patients with a K. pneumoniae liver abscess are at risk of developing endogenous Klebsiella pneumoniae endophthalmitis (EKE). Clinical manifestation of K. pneumoniae endophthalmitis are unique with posterior chamber becomes full of pus while anterior segment seem quiet. The authors presented a case of extremely rare presentation of endogenous bacterial endophthalmitis, who presented with choroidal mass. After receiving pars plana vitrectomy and intravitreal antibiotic injection, clinical condition improved. Despite aggressive treatment, the final visual outcome was generally poor. PMID- 22774631 TI - Mycobacterium fortuitum cutaneous infection from amateur tattoo. AB - A case of cutaneous Mycobacterium fortuitum infection after receiving an amateur tattoo is reported. A few days after tattooing, an otherwise healthy 25-year-old Thai male presented with multiple discrete erythematous papules confined to the tattoo area. He was initially treated with topical steroid and oral antihistamine without improvement. Skin biopsy was carried out, and the histopathology showed mixed cell granuloma with a foreign body reaction (tattoo color pigments). The acid-fast bacilli stain was positive. The tissue culture grew M. fortuitum two weeks later. He was treated with clarithromycin 1,000 mg/day and ciprofloxacin 1,000 mg/day for 10 months with complete response. From the clinical aspect, tattoo-associated rapidly growing mycobacterium infection might be difficult to differentiate from the pigment-based skin reactions. Skin biopsy for histopathology and tissue culture for Mycobacterium probably will be needed in arriving at the diagnosis. PMID- 22774632 TI - Orthostatic headache from spontaneous spinal cerebrospinal fluid leakage; diagnosed by heavily T2-weighted magnetic resonance myelography. AB - Orthostatic headache is derived from low cerebrospinal fluid (CSF) pressure as evidenced by cranial magnetic resonance myelography (MRM). This reports three cases of patients coming with orthostatic headache without previous obvious spine trauma. The first two cases had headache with radiating neck pain while the third case had headache with radiating pain to the eye sockets or occasional nausea. The third case was diagnosed from cranial MR imaging. The three cases were not done for CSF opening pressure measuring or criterion's method myelography, but had done T2-weighted MR. All of three cases had spinal epidural collections. The second case had meningeal diverticula. The present report found a possible site of leak in all cases. In the present report, T2-weighted MR myelography could avoid dural puncture. It was used as a non-radiation exposure investigating technique. This technique can be used as the first line of investigation prior to CTM, guiding a radiologist to seek the most likely site of leak during CTM study. PMID- 22774633 TI - Coexisting vulvar Paget's disease and mucinous carcinoma of the breast: a case report and review of the literature. AB - Vulvar Paget 'disease is the most common site of extramammary Paget's disease (EMPD). The disease frequently associated with the underlying invasive skin adnexal carcinoma or representing the migration of underlying internal malignancy, especially anorectal and genitourinary cancer, but the coexisting with primary breast cancer is rare. Herein, the authors report a case of a 46 year-old Thai woman who had vulvar Paget's disease with subsequent development of mucinous carcinoma of the breast. Interestingly, the overexpression of HER-2/neu in vulvar Paget's disease raises the additional option of anti-HER-2/neu antibody therapy in highly aggressive or recurrent disease. In conclusion, primary breast cancer should be of concern in patients with vulva Paget's disease, even though it is an uncommon association. PMID- 22774634 TI - [My life, my science]. PMID- 22774635 TI - [Research advances on aquaporins and vascular function regulation and related diseases]. AB - Aquaporins (AQPs), mainly distributed in epithelial and endothelial cells, are a family of channel-forming membrane proteins, originally confirmed to mediate the cellular water-transportation. AQPs are essential for maintaining homeostasis of the body water. Recently, studies have shown that AQPs may be involved in vascular function regulation and the development of related diseases, especially in cerebral ischemia, congestion heart failure, hypertension and tumor angiogenesis. Therefore, further studies are needed to elucidate mechanism accounting for the association between AQPs and vascular function related diseases, which may lead to novel approaches to the prevention and treatment of these diseases. In this review, we will discuss the expression and physiological roles of AQPs in vascular tissues and summarize recent progress in the relationship between AQPs and vascular function related diseases. PMID- 22774636 TI - [Microparticles, stem cells' new mechanism for tissue repair?]. AB - Though stem cell transplantation has been confirmed to be useful in repairing aging and diseased tissues, the underlying mechanism remains elusive. In addition to soluble molecules, cells-derived membrane microparticles (MPs) are considered as new mediators served in cross-talk communication among cells. MPs are tiny membrane coated subcellular vesicles released by a variety of cell types including stem cells. MPs may interact with target cells through specific receptor-ligand interactions and transfering proteins, bioactive lipids, mRNA and miRNA. Composition and function of stem cells derived MPs are highlighted in recent years. Here, we give an overview of MPs'composition, vesiculation and liberation mechanism, roles involved in communication exchages, and research progress in stem cells derived MPs. The report here might provide some novel information to highlight the stem cells therapy. PMID- 22774637 TI - [Progress in biological functions of nuclear receptors in Drosophila melanogaster]. AB - Nuclear receptors (NRs) belong to a superfamily of ligand-activated transcription factors that can bind directly to DNA and regulate expression of downstream target genes involved in avariety of important biological processes in organism, such as metabolism, reproduction and development. Drosophila have 21 NRs. They play crucial roles for Drosophila in regulating embryonic development, molting, metamorphosis, reproduction and metabolism. Here, we summarize the constitution of nuclear receptors,focusing on biological functions of themselve and their interactions. All these investigations will potentially supply new understanding of endocrine mechanism in insect. PMID- 22774638 TI - [Neurokinkin B and it's function on reproductive endocrine]. AB - Neurokinkin B (NKB) is a member of tachykinin family and plays a role mainly through its receptor NK3R. NKB and NK3R are wide spread through the neural system. Studies revealed that NKB has kinds of biological functions such as constringing the smooth muscle of hollow viscus, relaxing blood vessels, reducing mean arterial pressure, slowing heart rate, exciting in vitro spinal cord neurons of rats and astringing sphincter pupillae. For the past few years, people pay more and more attentions to the regulating action of NKB on reproductive endocrine and a lot of research are made to discuss the function of NKB in HPGA. This article summarizes the distribution and physiological function of NKB and NK3R, discusses their functions in reproductive endocrine. Future studies will be needed to determine the precise mechanism of NKB. PMID- 22774640 TI - [Progress of demyelinating animal models in the central nervous system]. PMID- 22774639 TI - [Hydrogen sulfide--a novel cardiac disease protector]. PMID- 22774641 TI - [Update on research of growth arrest-specific gene 6]. PMID- 22774642 TI - [Temperature-sensitive TRP ion channels as drug targets for neuropathic pain]. PMID- 22774643 TI - [Electrophysiological research of hypoxic pulmonary arterial hypertension]. PMID- 22774644 TI - [Obesity and related metabolic disease with the gut microflora]. PMID- 22774645 TI - [Recent advances in the molecular mechanisms of CIP2A]. PMID- 22774646 TI - [Angiotensin-converting enzyme 2 in the kidney]. PMID- 22774647 TI - [Research progress of the novel CO-donor CORMs and its bioactive properties]. PMID- 22774649 TI - [Decline of physiology]. PMID- 22774648 TI - [Relationship of beclin1 with autophagy and tumor]. PMID- 22774650 TI - What price ignorance? PMID- 22774651 TI - Diamond celebrations. PMID- 22774652 TI - Minimising the spread of infection in the operating department. AB - We live in a world of continuing advances in technology, surgical techniques and rapidly improving medicine. Despite these advances, diseases are continuing to thrive and cause infection both in the community and, more disturbingly, in hospitals. Damani (2003) states that medical care is more complex than ever before, and this has resulted in hospital acquired infections (HAls) increasing due to organisms which are resistant to antibiotics such as: methicillin resistant staphylococcus aureus (MRSA) and vancomyan resistant enterococci (VRE). Wilson (2006) explains that hospitals provide a particularly fertile breeding ground for resistant micro-organisms, due to the widespread exposure to antibiotics and the many opportunities that hospitals provide to transfer MRSA between vulnerable patients and into sites which are susceptible to infection, such as wounds and invasive devices. Damani (2003) emphasises again that the key to successful control of antimicrobial resistant pathogens in hospitals is good isolation techniques, and especially rigorous attention to hand hygiene by all members of staff who are in contact with patients affected or colonised with resistant pathogens. The aim should be to eliminate the infection as quickly as possible and to ensure that the patient's period of isolation is kept to a minimum. Advice and knowledge about the control of infection is therefore imperative. PMID- 22774653 TI - The story of anterior cruciate ligament reconstruction--part 2. AB - The first part of The story of anterior cruciate ligament reconstruction, was published in the previous issue of this journal, and the reader is encouraged to study both parts in order to become better acquainted with the subject. Those who have read the first part will remember that it concerned the historical developments surrounding the ligament's discovery, the acknowledgement of its function and the appreciation of the detrimental effects once it becomes damaged. It also described the efforts of the early pioneers who recognised the need to reestablish ligament function by ways of ligament repair or reconstruction with autologous tissue. The second part, presented here, explores the surgeons' quests to find the ideal graft material by experimenting with various synthetic materials, as well as those derived from animals (xenografts) and other human beings (allografts). It looks at historic efforts to stabilise an unstable knee by means of extra-articular reinforcements which were popular until not too long ago and reviews the developments of the various graft fixation methods available today. Furthermore it evaluates the influence of arthroscopy which revolutionised not just the procedure of ACL reconstruction but knee surgery in general, and also focuses on the more recent developments of double bundle techniques and the recreation of the ligament's native anatomy. PMID- 22774654 TI - The impact of late-starts and overruns on theatre utilisation rates. AB - The NHS Management Executive recommends that hospitals should aim to use 90% of planned theatre time and that theatre utilisation should be used as a key performance indicator. This study aims to investigate the impact of late-starts and overruns on theatre utilisation rates. Data were retrieved from a prospectively updated theatre database for all elective plastic surgical main theatre operating sessions carried out over a one year period. Theatre list utilisation was calculated as the percentage of the total allocated session time that was used for anaesthesia and operating. A total of 2,944 elective main theatre operations were performed in one year. Total theatre utilisation was 90.9%. Utilisation of lists starting less than one hour after the scheduled start time was similar to the utilisation of sessions starting more than one hour late (90.1% versus 91.7% respectively, p = 0.527). In contrast, overrunning lists demonstrated much higher utilisation rates than those that finished before the end of the session (96.7% versus 76.6% respectively, p < 0.001). The study shows that late-starts and overruns represent obvious sources of theatre inefficiency yet their impact on utilisation is misleading: overruns exaggerate theatre usage and late-starts have little impact upon it. We conclude that the use of utilisation as a marker of theatre performance requires caution. PMID- 22774655 TI - Targeted distribution of National Patient Agency Safer Practice Notice on throat packs. AB - Using an electronic questionnaire, we tested the effectiveness of professional networks for distributing a National Patient Safety Agency Safer Practice Notice, 'Reducing the risk of retained throat packs after surgery', issued in April 2009. Using professional networks for the targeted distribution of guidance to specific professional groups was found to be effective. PMID- 22774656 TI - Reducing mortality for high risk surgical patients in the UK. AB - Over 40 million surgical procedures are performed per annum in the USA and Europe, including several million patients who are considered to be high risk (Bennett-Guerrero et al 2003). Overall, the risk of death or major complications after surgery in the general surgical patient population is low, with a post operative mortality rate of less than1% during the same hospital admission (Niskanen et al 2001). PMID- 22774657 TI - Burrill Bernard Crohn. PMID- 22774658 TI - 'The sooner the better' for feeding milk to preterms. PMID- 22774659 TI - From iron lungs to family-centred care. PMID- 22774660 TI - Emotional labour: the challenges of working with children and cancer. AB - This article explains the concept of emotional labour and applies it to working with children with cancer. Emotional labour describes active management of the emotions, and the use of emotion as part of the work that is required in many jobs, particularly nursing. Although emotional labour is an important part of nursing work, it is often neglected or taken for granted. PMID- 22774661 TI - An account of nursing a child with complex needs in the home. AB - A children's nurse in the Republic of Ireland describes her experience working with children with complex needs in their homes, the preferred setting for their care. The varied duties involved in meeting essential, often complicated, requirements and gradually improving the quality of life of child and family are explored using Peplau's model of care. Career pathways for children's nurses in Ireland now include the development of community posts and planned support in the home for children with long-term illnesses and their caregivers. PMID- 22774662 TI - Providing information to children before and during venepuncture. AB - AIM: To explore the nature, process and consequences of giving information to children aged three to 11 years before and during venepuncture. METHOD: This was a non-participant, observational, qualitative study of 11 children and four healthcare professionals before and during venepuncture. The healthcare professionals were: a sister, a healthcare assistant, a junior doctor and a staff nurse. FINDINGS: There was little assessment of children's levels of knowledge of venepuncture and they received no information before the procedure. During the procedure, the children under six years of age only received information about the local anaesthetic cream during the application of the cream, not the venepuncture; the older children received information about the application of the cream and the venepuncture during both procedures. Practitioners used different language with the younger children when applying the local anaesthetic cream. Although the younger children did not appear distressed by the application of the cream, they appeared to be distressed by the venepuncture--more so than the older children--protesting and crying during the procedure. CONCLUSION: Some of the distress associated with venepuncture can be avoided if children are given information about the procedure in a way they can understand. PMID- 22774663 TI - Understanding care closer to home for ill children and young people. AB - AIM: To gather evidence to support the implementation of standard six of the National Service Framework for Children, Young People and Maternity Services (Department of Health and Department for Education and Skills 2004), which states that care should be provided as close to home as possible. METHODS: A mixed methods study comprising of a systematic review, a national survey of provision of care closer to home (CCTH), four in-depth, qualitative case studies and a cost analysis. FINDINGS: The systematic review suggests that CCTH is no less clinically effective than hospital care. Services identified by the survey fall into three distinct models of provision. Case study data show that families preferred CCTH, but staff face difficulties at organisational and practice levels. Cost analysis suggests there can be cost savings with CCTH, but several factors influence these. CONCLUSION: CCTH may be an effective and feasible option for children and young people who are ill. PMID- 22774665 TI - "Surprise" rise in agency nurse use. PMID- 22774664 TI - "Stop the blame game to raise standards of care". PMID- 22774667 TI - "HCAs deserve clarity over their role before mandatory regulation". PMID- 22774666 TI - Training innovation boosts basic care skills. PMID- 22774669 TI - "Embrace the opportunities that advanced practice offers". PMID- 22774668 TI - Get on the right side of the sharps practice law. PMID- 22774670 TI - Exploring the benefits and challenges of telehealth. AB - Technology is likely to transform the way care is delivered at home and in the community. This article outlines its benefits for patients and challenges for nurses. PMID- 22774671 TI - Advanced nursing. Part 1: The development of advanced nursing roles. AB - This first in a three-part series on advanced nursing practice reviews its historical evolution. Part 2, to be published next week, reviews the introduction of a governance framework, while part 3 explores the future of advanced practice and how it may shape nursing career structures. PMID- 22774672 TI - Health checks for people with learning disabilities. PMID- 22774673 TI - Using reflective practice in frontline nursing. AB - Reflection on practice is a key skill for nurses. Engaging in regular reflection enables practitioners to manage the personal and professional impact of addressing their patients' fundamental health and wellbeing needs on a daily basis. This article briefly reviews the theoretical background underpinning the idea of reflective practice. A simple, three-step model for practical reflection is presented, which is based on theory and grounded in practice. The three-stage cycle is illustrated with a fictional clinical example to show how this reflective method can make a difference in busy practice settings. PMID- 22774674 TI - Managing osteoporosis in a rural community. AB - Managing long-term conditions, such as osteoporosis in a rural community, presents particular challenges. This article describes how a specialist service identified patients at high risk of fragility fracture and raised awareness of bone health. PMID- 22774676 TI - How models help staff to plan care. PMID- 22774675 TI - Out of Africa: contrast of care. PMID- 22774677 TI - The one-trial learning controversy and its aftermath: remembering Rock (1957). AB - In 1957 Irvin Rock published an article in the American Journal of Psychology igniting a controversy that dominated the field of verbal learning for the next 8 years before mostly burning out. Rock published 2 paired-associate learning experiments in which he compared performance of a control group that learned a constant list of pairs to the criterion of one perfect trial with an experimental group in which forgotten pairs on each trial were dropped and replaced on the next trial with new pairs. That is, on each trial for experimental subjects, pairs that were correctly recalled were maintained in the next trial, whereas pairs that were not recalled were dropped and replaced randomly with new pairs from a large pool. Surprisingly, Rock found that the 2 groups took the same number of trials to reach criterion. He concluded that learning occurred not with a gradual, incremental increase in strength of memory traces but rather in an all or-none fashion. Rock's conclusions rocked the world of verbal learning, because all theories followed a gradualist assumption. However, Estes (1960) published research that led him to the same conclusion shortly thereafter. We recount these developments and discuss how the verbal learning establishment rose up to smite down these new ideas, with particular ferocity directed at Rock. Echoing G.A. Miller (1963), we conclude with a note of sympathy for Rock's and Estes's positions and muse about why their work was so summarily dismissed. The important question they raised--the nature of how associations are learned--remains unanswered. PMID- 22774678 TI - 125 years of intelligence in the American Journal of Psychology. AB - A survey is made of intelligence research in the 125 years of The American Journal of Psychology. There are some major articles of note on intelligence, especially Spearman's (1904a) article that discovered general cognitive ability (g). There are some themes within intelligence on which articles appeared over the years, such as processing speed, age, and group differences. Intelligence has not been a major theme of the journal, nor has a differential approach to psychology more generally. There are periods of time--especially the 1970s- during which almost no articles appeared on intelligence. The key articles and themes on intelligence differences are discussed in detail. PMID- 22774679 TI - Research in visual pattern recognition: the enduring legacy of studies from the 1960s. AB - This article highlights some research in visual pattern perception that was published in the American Journal of Psychology in the 1960s. Although visual perception research has changed substantially since then, and the term visual pattern recognition is no longer in widespread use, the six articles presented here are some of the most influential of those published by the Journal in its long history. The research is described with an emphasis on how a particular publication influenced others and the field in general. PMID- 22774680 TI - The standard model for perceived magnitude: a framework for (almost) everything known about it. AB - The psychophysics of perceived magnitude entails three aspects of sensory systems: range of sensitivity (dynamic range [DR]), resolving power (the capacity to resolve small changes in stimulus intensity), and the form of the function relating perceived magnitude to signal strength throughout the DR. A simple model is proposed that integrates what is known about all three aspects into a single framework. According to the model, perceived magnitude is a power function of stimulus strength (S. S. Stevens, 1956), and both the exponent of that function and a measure of resolving power are inversely related to the log of DR (R. Teghtsoonian, 1971). The DR is thought to have a characteristic value for each sensory system and may be estimated directly by measurement of upper and lower limits, or indirectly by estimating the exponent of the power function under optimal conditions. A central feature of the model is that all DRs are assumed to be subjectively equal. It is also suggested that the impression of perceived magnitude may be mediated by a single mechanism, regardless of the sensory system that is activated. It remains to be seen whether brain science is able to identify a neural basis for such a mechanism. PMID- 22774681 TI - Recommending action more than inaction when either decision fails: which norm underlies this process? AB - Norm theorists' assumption that action is abnormal compared with inaction was revisited. Two experiments tested the opposite prediction, that action is construed as the descriptive norm and therefore is less mutable than inaction and should be more recommended for undoing a negative outcome. Participants both undid a person's negative outcome by recommending an alternative decision and rated the intensity of regret he or she was likely to feel. The focal outcomes were categorized as resulting from a conjunction of 4 decisions, including action, inaction, or a combination of both. An abnormality index was constructed based on the distance between the decision implemented and the decision recommended. Overall, action was most frequently recommended as an alternative to most of the other decisions. Mixed action-inaction instead of inaction was highly recommended as an alternative when action failed (Experiment 1), but when explicitly presented as the descriptive norm, inaction was highly recommended as an alternative to action (Experiment 2). The numeric distance between action and the recommended alternatives was shorter than that between inaction and its alternatives, suggesting that the former is normal. However, the actor was expected to experience regret of equal intensity regardless of how the outcome originated. The recommendation responses support the descriptive norm perspective. PMID- 22774682 TI - Effect of context on performance approach orientation. AB - We proposed and tested a theoretical model that argues that different work contexts influence the relationship between performance approach orientation and work performance. Across three studies and three different types of work performance, results consistently supported a theorized interaction between performance approach orientation and rewarding climate. Two self-rating studies showed generally similar interactions, with some important differences in the significance of the simple slopes. Larger differences emerged between the self rating and a supervisor rating study. The present research supports a model in which type of work (part time vs. full time), rewarding climate, the criterion of performance (supervisor vs. self-rating), and type of work performance are important contextual components of a model relating performance approach orientation to work performance. PMID- 22774683 TI - Transference in view of a classical conditioning model. AB - This article presents a qualitative metasynthetic study, addressing 33 transference case studies, that investigates the interrelationship of the transference concept from psychoanalysis and cognitive-behavioral concepts in an attempt to construct a theoretical platform for clinical integration. Relationship between categories analysis was used to compare Luborsky's (1998) transference components (wish, response from other, and response of self) and cognitive-behavioral ones. Results showed reciprocal relations between transference and classical conditioning. Furthermore, explicit occurrences of distorted thinking due to overgeneralization were found in more than 90% of the cases. A conceptual model describes transference as a conditioned response activated by thematic conditioning, a particular case of classical conditioning that repeatedly pairs a given interpersonal situation with internal thematic stimuli, thus shaping the person's narrative. Theoretical and practical implications are discussed as well. PMID- 22774684 TI - Building false memories without suggestions. AB - People can come to remember doing things they have never done. The question we asked in this study is whether people can systematically come to remember performing actions they never really did, in the absence of any suggestion from the experimenter. People built LEGO vehicles, performing some steps but not others. For half the people, all the pieces needed to assemble each vehicle were laid out in order in front of them while they did the building; for the other half, the pieces were hidden from view. The next day, everyone returned for a surprise recognition test. People falsely and confidently remembered having carried out steps they did not; those who saw all the pieces while they built each vehicle were more likely to correctly remember performing steps they did perform but equally likely to falsely remember performing steps they did not. We explain our results using the source monitoring framework: People used the relationships between actions to internally generate the missing, related actions, later mistaking that information for genuine experience. PMID- 22774685 TI - Legionella pneumonia and dental unit waterlines. PMID- 22774687 TI - Ionizing radiation regulations and the dental practitioner: 2. Regulations for the use of X-rays in dentistry. AB - The first article in this series covered radiation hazards and protection. To minimize the potential harmful effects of X-rays, legislation has been introduced by a number of countries including the European Union. PMID- 22774688 TI - Invisalign, an innovative invisible orthodontic appliance to correct malocclusions: advantages and limitations. AB - Tooth movement may be achieved by the use of sequential positioners made by altering tooth positions on set-up models to simulate progress of treatment. The principle is based upon Kesling's positioner concept of 1945, though its subsequent application to splint therapy was labour intensive and did not result in precise tooth movement. Invisalign was developed by Align Technology, Inc (Santa Clara, CA, USA) in 1997 by applying 3-D imaging technology to overcome these problems, and permitting customization on a large scale. Their system offers significant advantages, but still suffers from limitations which are discussed in this article. PMID- 22774686 TI - Endodontic 'solutions' part 1: a literature review on the use of endodontic lubricants, irrigants and medicaments. AB - Endodontic lubricants, irrigants and medicaments help prepare and disinfect root canal systems (RCS) but primary and secondary cases involve different microbes and therefore it is unlikely that one protocol will be effective for both case types. Each individual 'solution' or sequence of'solutions' could play a significant role in each case type, but there are no detailed published guidelines in existence. To help inform clinical practice it was decided to undertake a literature review followed by a UK and Republic of Ireland wide audit on current endodontic'solution' usage within dental schools. The literature review was undertaken under the following headings: pre-op oral rinse; file lubricants; root canal irrigants and intracanal medicaments and provides an evidence base for protocol development for both primary and retreatment cases.The audit project and the protocols developed from the findings of both the literature review and audit will be presented in Part 2. PMID- 22774689 TI - The talon cusp--an uncommon anomaly. AB - Talon cusps are an uncommon dental anomaly of odontogenic origin. Talon cusps can also present with other dental anomalies, however these have been infrequently reported in the literature.The following is a report of two cases in which talon cusps were detected in combination with two distinct dental anomalies: an ectopic canine and transposition. PMID- 22774691 TI - Ozone and caries: a review of the literature. AB - Ozone, either in gaseous form or as ozonated water, has been available for use as a treatment for dental caries for a decade. This paper reviews the literature on the subject by examining the findings of publications in the peer review literature. Eighteen papers were identified by a literature search. From the review of these, it was concluded that, while some laboratory studies and some short duration clinical studies have suggested that ozone may be effective in the treatment of root caries or killing of oral micro-organisms, the clinical evidence for the use of ozone in treatment of caries is not compelling. PMID- 22774690 TI - Bleeding disorders seen in the dental practice. AB - Dentists may encounter patients with various types of bleeding disorders in their daily practice. Initial recognition of such bleeding disorders and their possible systemic causes, as well as knowing when to refer those cases to secondary care, plays a crucial and important role in reducing potential complications and negative side-effects. This article will give an account of the most common bleeding disorders that dentists might find in their daily dental practice. This will be followed by another article that will cover the management of congenital and acquired disorders found in the dental practice. PMID- 22774692 TI - Interdisciplinary management in the paediatric patient: restoration of a complicated crown-root fracture. AB - Complicated crown-root fractures in permanent teeth present both patient-centred and restorative problems when treating the adolescent. This case highlights an alternative and conservative technique for the management of a traumatically involved maxillary left central incisor in a 12-year-old boy. The injury was successfully managed through an interdisciplinary approach using a combination of endodontics, minor oral surgery and orthodontics. The approach resulted in utilizing the patient's own tooth fragment to facilitate restoration back into successful function and aesthetics with the absence of any pathological changes. PMID- 22774693 TI - Recurrent exophytic growth on maxillary posterior edentulous alveolar ridge--a diagnostic challenge. AB - Accurate diagnosis of recurrent intra-oral exophytic lesions require a thorough history, meticulous clinical examination and the experience of assessing these lesions, because they are not commonplace. Despite this, instituting the correct diagnosis tests the skills of an oral medicine expert. Therefore, the same is all the more challenging for a general practitioner who may encounter these lesions without any significant experience. The importance of diagnosing such lesions cannot be understated, as they may represent a myriad of conditions ranging from seemingly innocuous benign pathologic processes to much more sinister ones, like oral malignancy; occasionally some of these lesions may manifest atypically. Such atypical presentations may cloud the diagnostic process. Here a case uncharacteristic of the condition it represented is reported with the aim of increasing awareness of the diagnosis of such lesions. PMID- 22774694 TI - Prosthodontic rehabilitation of patients with orofacial defects. AB - In 2007 in the UK, 5410 people were diagnosed with an oral cancer. It is therefore imperative that all dentists, medical practitioners and dental care practitioners are vigilant when examining the oral cavity so that any suspicious ulcers, swellings or changes in colour of the mucosa are referred at the earliest stage. To give the patient the best prognosis with an orofacial defect following tumour removal or trauma, it is most important to have the appropriate skills in a multidisciplinary team. The management of patients comprises pre-surgical, surgical and post-surgical phases. PMID- 22774695 TI - Oral cancer: comprehending the condition, causes, controversies, control and consequences: 16. Infections. PMID- 22774696 TI - Technique tips--a 'get out of jail' material. PMID- 22774697 TI - Physical signs for the general dental practitioner. Case 94. Systemic sclerosis (scleroderma). PMID- 22774698 TI - IJOM celebrates the 40th anniversary of the International Association of Orofacial Myology (IAOM). PMID- 22774699 TI - International Association of Orofacial Myology History: origin - background - contributors. AB - These milestones of the history of the International Association of Orofacial Myology (IAOM), its founders and many of the major contributors are presented in this article. Personal reflections are provided by individuals who were instrumental in the formation of IAOM. PMID- 22774700 TI - Myths that persist about orofacial myology. AB - This article addresses many myths that have persisted over the years in dentistry and orofacial myology regarding the nature of orofacial myofunctional disorders (OMD's). Myths include 1) the concept that the term "tongue thrusting" includes the rest posture; 2) that there is an excessive amount of pressure exerted against the anterior teeth in swallows, that swallowing pressures add up, and the frequency of swallowing has an impact on the dentition; 3) the idea that the tongue is the strongest muscle in the body; 4) the view that a muscle will be the winner in any tug of war between muscle and bone; 5) the claim that a tongue thrust can cause an open bite malocclusion; 6) the claim that a tongue thrust can cause a Class II malocclusion; 7) the claim that the tongue molds the palatal vault; 8) the notion that a low tongue tip posture at rest presents a problem; and 9) the claim that OMD's represent a muscle imbalance that can be brought into balance with therapy. Each of these false claims or "myths" is discussed and corrected, with the positive acknowledgement that clinicians are abandoning the incorrect notion of muscle balance and imbalance as had been claimed previously. PMID- 22774701 TI - Influence of mandibular morphology on the hyoid bone in atypical deglutition: a correlational study. AB - OBJECTIVE: evaluate the possible correlation with the radiographic position of the hyoid bone and mandibular angle in lateral radiographs of children with atypical deglutition. STUDY DESIGN: This was an observational study using cephalometric analysis of lateral teleradiographs for the distances of H-MP (hyoid to mandibular plane). Spearman's correlation analysis was performed with MA (mandibular angle) in two groups: the experimental group with atypical deglutition and the control group normal deglutition. Both groups included subjects in mixed dentition stage. RESULTS: there was a significant moderate negative correlation between MA (mandibular angle) and hyoid bone (H-MP) in the normal group (R = -0.406, p = 0.021). However, there was no significant correlation between the MA and H-MP (R = 0.029, p = 0.83) in the group with atypical deglutition. CONCLUSION: there is a moderate negative correlation between the position of the hyoid bone and mandibular angle in the group of normal swallowing and there is no correlation between variables H-MP and MA in the group of atypical swallowing. PMID- 22774702 TI - Standardization of the registration and analysis of mastication: proposal for clinical application. AB - The purpose of this study was to verify the inter-rater agreement level as a means of obtaining an efficiency measure of a standard mastication evaluation through video recordings. The studied population included oral breathing children and teenagers with maxillary atresia. The chewing aspects studied were mode of chewing and preferential chewing side. A white tag was placed on half the subjects' chins while the recordings were made. Two expert evaluators analyzed 54 video recordings at regular viewing speed. The lead author analyzed the same video recordings both at reduced speed and at reduced speed linked through graphical computing techniques. The analysis was conducted on chewing cycles with the viewing angle of the frontal plane. Findings indicated that when comparing the data for the three manners of watching the video recordings, the agreement level was higher for videos with the tag on the chin watched at reduced speed. It was also determined that alternating and bilateral mastication modes were prevalent (64.7%) in this sample. PMID- 22774703 TI - Feeding therapy for children with food refusal. AB - Disabled children suffer not only from their primary disease, but also from other complications, including food refusal. The purpose of this study was to elucidate the relationship between these conditions and food refusal in disabled children. The effectiveness of feeding therapy in treating food refusal was also examined. The study subjects were 67 disabled children (35 boys and 32 girls; mean age at initial examination: 6.5 years, SD: 6.0 years) who attended the Nippon Dental University Hospital between April 2004 and August 2008. Of them, the 13 subjects who were diagnosed as those who refused food received feeding therapy combined with desensitization therapy for hypersensitivity. Approximately 20% of the subjects showed food refusal symptoms. Primary disease, respiratory impairment and gastroesophageal reflux were not causes of food refusal in this population. There was a significant relationship between food refusal and hypersensitivity (p = 0.021). After receiving feeding therapy, six of the seven subjects with hypersensitivity but without dysphagia at initial examination recovered from food refusal. Food refusal did not significantly correlate with tube feeding. Hypersensitivity and/or tube feeding may induce food refusal. For subjects with these conditions, feeding therapy combined with desensitization therapy is effective in achieving recovery from food refusal. PMID- 22774704 TI - Horns, whistles, bite blocks, and straws: a review of tools/objects used in articulation therapy by Van Riper and other traditional therapists. AB - The use of tools and other objects in articulation therapy has been bundled into new groups of activities called "nonspeech oral motor exercises" (NSOME) and 'nonspeech oral motor treatments' (NSOMT) by some authors. The purveyors of these new terms suggest that there is no proof that such objects aid speech learning, and they have cautioned students and professionals about their use. Speech language pathologists are trying to reconcile these cautions with basic Van Riper type therapy routines. The purpose of this literature review was to summarize the ways in which tools/objects were used by Van Riper and other speech professionals between 1939 and 1968. Fourteen textbooks were selected for review. Van Riper and other developers of traditional articulation therapy regularly used a wide variety of tools/objects in articulation therapy. Tools/objects were used when other auditory, linguistic, and cognitive means failed to stimulate correct phoneme productions. To call these activities "non-speech" methods seems to misrepresent the historic purpose objects have served in articulation therapy. More empirical research is required in this area. PMID- 22774705 TI - The MMPI-2 L scale, reporting uncommon virtue, and predicting police performance. AB - The present study investigated the use of the Minnesota Multiphasic Personality Inventory (MMPI)-2 L (Lie) scale in the preemployment selection of police officers. In a prior article, Weiss, Davis, Rostow, and Kinsman (2003) found that high L scale scores are associated with a number of performance problems in law enforcement officers. These investigators recommended a L scale raw score cutoff of 8 when making hiring decisions. The present study sought to explore the usefulness of this recommendation by analyzing data from 4348 officers who had taken the MMPI-2 as a condition of preemployment and had follow-up data on performance provided by their supervisors. Results indicated that officers with L scale raw scores of 8 or higher had significantly more performance problems than those who had scores of 7 or below. Similar results were obtained when cut points of 7 and 9 were used. These results were robust insofar as they remained significant when other factors potentially related to the L scale, particularly level of education, ethnicity, and scores on the 10 MMPI-2 Clinical Scales, were controlled for in the analyses. Implications of these findings for police psychological evaluations are discussed. PMID- 22774758 TI - Long-lived charge-separated states in ligand-stabilized silver clusters. AB - Recently developed synthesis methods allow for the production of atomically monodisperse clusters of silver atoms stabilized in solution by aromatic thiol ligands, which exhibit intense absorption peaks throughout the visible and near IR spectral regions. Here we investigated the time-dependent optical properties of these clusters. We observed two kinetic processes following ultrafast laser excitation of any of the absorption peaks: a rapid decay, with a time constant of 1 ps or less, and a slow decay, with a time constant that can be longer than 300 ns. Both time constants decrease as the polarity of the solvent increases, indicating that the two processes correspond to the formation and recombination, respectively, of a charge-separated state. The long lifetime of this state and the broad optical absorption spectrum mean that the ligand-stabilized silver clusters are promising materials for solar energy harvesting. PMID- 22774759 TI - Repopulation of ganciclovir-resistant cytomegalovirus by wild-type virus. AB - We report a patient in whom ganciclovir (GCV)-resistant cytomegalovirus (CMV) was replaced by wild-type virus after discontinuation of GCV/valganciclovir and review other similar cases. Repopulation by wild-type virus may occur soon after discontinuation and may be fostered by discontinuing GCV altogether rather than continuing it in combination with foscarnet when treating patients with GCV resistant CMV disease. PMID- 22774760 TI - The efficacy of positive behavioural support with the most challenging behaviour: the evidence and its implications. AB - BACKGROUND: Positive behaviour support (PBS) is behaviour analysis applied in support of people with challenging behaviour. Questions have been raised as to PBS effectiveness, costs, and accessibility. METHOD: Outcome studies meeting specified criteria for PBS were selected for review. All told, 12 outcome studies encompassing 423 cases were included. RESULTS: This review showed that PBS was effective with both severe and high-rate behaviour problems, was cost-effective, used a methodology that was easily trained and widely disseminated, and worked in institutional settings in which the most difficult problems are thought to be, as well as in the community. CONCLUSIONS: The major implication of this review is that practitioners may be obligated to use PBS when faced with the need to develop a plan of support given the ethical principle of using the least restrictive method consistent with the right to effective treatment. PMID- 22774761 TI - Preparation of copolymer paclitaxel covalently linked via a disulfide bond and its application on controlled drug delivery. AB - A novel controlled drug delivery system based on copolymer covalently linked paclitaxel via a disulfide bond was constructed. Copolymer with poly(ethylene glycol) (PEG) side chains and carboxyl groups on the backbone was prepared by radical copolymerization of tert-butyl acrylate and poly(ethylene glycol) methyl ether acrylate, followed by selectively hydrolyzing tert-butyl groups to carboxyl groups. Utilizing the carboxyl group as an active reaction site, paclitaxel, a well-known chemotherapeutic drug, could be covalently linked to the backbone of a copolymer via a disulfide bond, and the loading content of paclitaxel could reach up to 32 wt %. In aqueous solution, this drug-loaded copolymer could self assemble into a spherical micelle, with the hydrophobic drug as the core and hydrophilic PEG as the shell. The mean diameter of the micelles evaluated by transmission electron microscopy (TEM) and dynamic light scattering (DLS) was approximately 60 nm. The in vitro cytotoxicity experiments showed that the copolymer was biocompatible and suitable to use as a drug carrier. After covalently loading the drug, the copolymer showed apparent cytotoxicity to OS-RC 2 cells (kidney tumor cells) and low cytotoxicity to macrophage cells (human normal cells), indicating that the disulfide bond was stable in human normal cells, but would be broken in tumor cells. This selective bond scission behavior is potentially favorable for reducing the toxic and side effects of chemotherapeutic drugs. PMID- 22774762 TI - Psychosocial and somatic outcomes of sleep problems in children: a 4-year follow up study. AB - BACKGROUND: Inadequate sleep in children relates to medical and psychosocial problems. However, not much is known about the effects of sleep problems persisting from pre-school to school age on somatic and psychosocial symptoms. OBJECTIVES: To examine the associations between sleep disturbances and psychosocial symptoms, somatic complaints, medical problems at school age. METHODS: This was a population-based 4-year follow-up study of sleep problems in Finnish children (n = 470). Parents filled in Sleep Disturbance Scale for Children during pre-school and school years. Children were categorized into four groups: no sleep problems, sleep problems only at pre-school or only at school age, and persistent sleep problems. At follow-up the parents filled in Child Behavior Checklist and a background questionnaire. RESULTS: The children with persistent sleep problems (9%) had a 16-fold risk of having psychosocial symptoms on subclinical/clinical range compared with the children without sleep problems. The psychosocial symptoms that were related strongest to prolonged sleep problems were aggression, social and attention problems, and anxious/depressed mood. Also, somatic complaints (ninefold risk) and medical problems (P < 0.001) were typical for children with persistent sleep problems. CONCLUSIONS: Persistent sleep problems in children associate with high levels of psychosocial, somatic and medical problems. In paediatric health care more attention should be paid to recognizing, monitoring of the persistence and treatment of sleep problems before school transition period. PMID- 22774763 TI - Systematic review of reviews of behavioural HIV prevention interventions among men who have sex with men. AB - Men who have sex with men (MSM) remain one of the groups most at risk of HIV. The growing evidence-base on behavioural HIV prevention interventions includes systematic review-level evidence, including reviews specific to MSM populations. Here, we provide an up-to-date review of these systematic reviews in which we examined the effectiveness of behavioural HIV prevention interventions among MSM. A systematic search of electronic databases, including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, PsycInfo, from January 2000 to October 2010, along with hand searches of the reference lists of retrieved documents were conducted. Inclusion criteria included: study design limited to systematic reviews and meta-analyses; methodological quality; and review to focus on MSM and behavioural interventions. A narrative synthesis was conducted. Across the four included meta-analyses (102 studies; 52 independent studies), there was strong and consistent evidence for group- and community-level interventions being associated with reductions in UAI (27-30% and 30%, respectively) and increases in condom use amongst MSM, but inconsistent evidence for the effectiveness of individual-level interventions. Skills-building, trained professionals delivering the training and theory-based interventions were also consistently effective. The inherent limitations of the review of review method within a changing health domain meant it was difficult to develop contemporary and directly transferable guidance to HIV prevention policy development. However, the analysis does demonstrate a need for a step change in the kinds of data that are collated in the development of future systematic reviews of HIV prevention interventions among MSM. PMID- 22774764 TI - Fostering team creativity: perspective taking as key to unlocking diversity's potential. AB - Despite the clear importance of team creativity for organizations, the conditions that foster it are not very well understood. Even though diversity, especially diversity of perspectives and knowledge, is frequently argued to stimulate higher creativity in teams, empirical findings on this relationship remain inconsistent. We have developed a theoretical model in which the effect of a team's diversity on its creativity is moderated by the degree to which team members engage in perspective taking. We propose that perspective taking helps realize the creative benefits of diversity of perspectives by fostering information elaboration. Results of a laboratory experiment support the hypothesized interaction between diversity and perspective taking on team creativity. Diverse teams performed more creatively than homogeneous teams when they engaged in perspective taking, but not when they were not instructed to take their team members' perspectives. Team information elaboration was found to mediate this moderated effect and was associated with a stronger indirect effect than mere information sharing or task conflict. Our results point to perspective taking as an important mechanism to unlock diversity's potential for team creativity. PMID- 22774767 TI - A photochemical route to 2-substituted benzo[b]furans. AB - 2-Substituted benzo[b]furans were synthesized by a one-step metal-free photochemical reaction between 2-chlorophenol derivatives and terminal alkynes by tandem formation of an aryl-C and a C-O bond via an aryl cation intermediate. The mild conditions and the application to chlorophenols rather of the more expensive bromo or iodo analogues makes this procedure environmentally convenient. PMID- 22774769 TI - Rictor regulates phosphorylation of the novel protein kinase C Apl II in Aplysia sensory neurons. AB - Rapamycin-insensitive companion of TOR (Rictor) is a conserved component of target of rapamycin complex 2 (TORC2), a complex implicated in phosphorylation of a number of signal transduction-related kinases, including protein kinase Cs (PKCs) at their 'hydrophobic' site in the carboxy-terminal extension domain. In the marine mollusk, Aplysia californica, an increase in phosphorylation of the novel PKC, Apl II, at the hydrophobic site is associated with a protein synthesis dependent increase in synaptic strength seen after continuous application of serotonin. To determine if Rictor plays a role in this increase, we cloned the Aplysia ortholog of Rictor (ApRictor). An siRNA-mediated decrease in ApRictor levels in Aplysia sensory neurons led to a decrease in the phosphorylation of PKC Apl II at the hydrophobic site suggesting a role for ApRictor in hydrophobic site phosphorylation. However, over-expression of ApRictor was not sufficient to increase phosphorylation of PKC Apl II. Continuous application of serotonin increased phosphorylation of PKC Apl II at the hydrophobic site in cultured sensory neurons, and this was blocked by Torin, which inhibits both TORC1 and TORC2. Over-expression of ApRictor did not lead to change in the magnitude of serotonin-mediated phosphorylation, but did lead to a small increase in the membrane localization of phosphorylated PKC Apl II. In conclusion, these studies implicate Rictor in phosphorylation of a novel PKC during synaptic plasticity and suggest an additional role for Rictor in regulating the localization of PKCs. PMID- 22774768 TI - The role of macrophages in healing the wounded lung. AB - Acute tissue injury is often considered in the context of a wound. The host response to wounding is an orchestrated series of events, the fundamentals of which are preserved across all multicellular organisms. In the human lung, there are a myriad of causes of injury, but only a limited number of consequences: complete resolution, persistent and/or overwhelming inflammation, a combination of resolution/remodelling with fibrosis or progressive fibrosis. In all cases where complete resolution does not occur, there is the potential for significant ongoing morbidity and ultimately death through respiratory failure. In this review, we consider the elements of injury, resolution and repair as they occur in the lung. We specifically focus on the role of the macrophage, long considered to have a pivotal role in regulating the host response to injury and tissue repair. PMID- 22774770 TI - Effect of different anticoagulants on multiple electrode platelet aggregometry after clopidogrel and aspirin administration in patients undergoing coronary stent implantation: a comparison between citrate and hirudin. AB - Outcomes of platelet function tests are highly dependent on the type of blood anticoagulant used. The primary objective of this study was to clinically evaluate the platelet function after dual antiplatelet therapy using two different types of anticoagulant (citrate and hirudin). We compared data obtained from multiple electrode platelet aggregometry (MEA) with reference to light transmission aggregometry (LTA) and VerifyNow (VN) assays. Blood samples were obtained from 119 patients on dual antiplatelet therapy at the time of PCI (PCI) and the following morning (post-PCI). The platelet function tests were performed using two anticoagulated (citrate or hirudin) blood types for MEA as well as citrated blood for LTA and VerifyNow assays. ADP-induced MEA values at PCI for citrated and hirudinated anticoagulants were 36.5 +/- 14.3 AUC and 41.4 +/- 18.2 AUC (p = 0.021) and post-PCI values were 28.2 +/- 11.9 AUC and 28.3 +/- 12.8 AUC (p = 0.95). Additionally, AA-induced MEA values at PCI by citrated and hirudinated blood was 13.4 +/- 7.3 AUC and 17.6 +/- 13.4 AUC (p < 0.01). Post-PCI AA-induced MEA values were 12.0 +/- 6.7 AUC and 13.5 +/- 8.5 AUC (p = 0.12), respectively. Significant correlations were observed between the two anticoagulants used for MEA and LTA or VN values under ADP-induced platelet stimulation. Citrate tubes are clinically adequate for MEA assays and provide a more economical alternative to hirudin for early and/or delayed phases after clopidogrel-loading doses. PMID- 22774771 TI - A relatively brief exposure to environmental enrichment after experimental traumatic brain injury confers long-term cognitive benefits. AB - It is well established that a relatively brief exposure to environmental enrichment (EE) enhances motor and cognitive performance after experimental traumatic brain injury (TBI), but it is not known whether the benefits can be sustained after EE is discontinued. To address this important rehabilitation relevant concern, anesthetized rats received a controlled cortical impact (CCI) or sham injury, and for phase 1 of the experiment were randomly assigned to either 3 weeks of EE or standard (STD) housing. Neurobehavioral outcome was assessed by established motor and cognitive tests on postoperative days 1-5 and 14-18, respectively. Beam-balance and spatial learning were facilitated in the TBI + EE more than the TBI + STD group (p<0.0001). In phase 2 of the experiment, half of the rats in EE were transferred to STD conditions (TBI + EE + STD and sham + EE + STD), and neurobehavior was re-assessed once per month for 6 months. The TBI + EE and TBI + EE + STD groups performed markedly better in the water maze than the TBI + STD group (p<0.0001), and did not differ from one another (p=0.53). These data replicate those of several studies from our laboratory showing that EE enhances recovery after CCI injury, and extend those findings by demonstrating that the cognitive benefits are maintained for at least 6 months post-rehabilitation. The persistent benefits shown with this paradigm provide further support for EE as a pre-clinical model of rehabilitation that can be further explored, either alone or in combination with pharmacotherapies, for optimal neurorehabilitation after TBI. PMID- 22774773 TI - Health impact assessment of liquid biofuel production. AB - Bioethanol and biodiesel as potential substitutes for fossil fuels in the transportation sector have been analyzed for environmental suitability. However, there could be impacts on human health during the production, therefore adverse health effects have to be analyzed. The aim of this study is to analyze to what health risk factors humans are exposed to in the production of biofuels and what the size of the health effects is. A health impact assessment expressed as disability adjusted life years (DALYs) was conducted in SimaPro 7.1 software. The results show a statistically significant lower carcinogenic impact of biofuels (p < 0.05) than fossil fuels. Meanwhile, the impact of organic respirable compounds is smaller for fossil fuels (p < 0.05) than for biofuels. Analysis of inorganic compounds like PM10,2.5, SO2 or NO(x) shows some advantages of sugar beet bioethanol and soybean biodiesel production (p < 0.05), although production of sugarcane bioethanol shows larger impacts of respirable inorganic compounds than for fossil fuels (p < 0.001). Although liquid biofuels are made of renewable energy sources, this does not necessary mean that they do not represent any health hazards. PMID- 22774772 TI - Pharmacological characterization of the peripheral FAAH inhibitor URB937 in female rodents: interaction with the Abcg2 transporter in the blood-placenta barrier. AB - BACKGROUND AND PURPOSE: URB937 is a peripherally restricted inhibitor of the anandamide-deactivating enzyme fatty-acid amide hydrolase (FAAH). Despite its limited access to the CNS, URB937 produces marked antinociceptive effects in rodents. URB937 is actively extruded from the CNS by the ATP-binding cassette (ABC) membrane transporter, Abcg2. Tissue Abcg2 levels are markedly different between males and females, and this transporter is known to limit the access of xenobiotics to the fetoplacental unit in gestating female rodents. In the present study, we investigated the tissue distribution and antinociceptive properties of URB937 in female mice and rats. EXPERIMENTAL APPROACH: We studied the systemic disposition of URB937 in female mice and the antinociceptive effects of this compound in models of visceral (acetic acid-induced writhing) and inflammatory nociception (carrageenan-induced hyperalgesia) in female mice and rats. Furthermore, we evaluated the interaction of URB937 with the blood-placenta barrier in gestating mice and rats. KEY RESULTS: Abcg2 restricted the access of URB937 to the CNS of female mice and rats. Nevertheless, URB937 produced a high degree of antinociception in female mice and rats in models of visceral and inflammatory pain. Moreover, the compound displayed a restricted access to placental and fetal tissues in pregnant mice and rats. CONCLUSIONS AND IMPLICATIONS: Peripheral FAAH blockade with URB937 reduces nociception in female mice and rats, as previously shown for males of the same species. In female mice and rats, Abcg2 limits the access of URB937, not only to the CNS, but also to the fetoplacental unit. LINKED ARTICLES This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue-8. PMID- 22774774 TI - Comparison of the response to treatment between Asian and Caucasian men with benign prostatic hyperplasia: long-term results from the combination of dutasteride and tamsulosin study. AB - The Combination of Avodart and Tamsulosin study was a 4-year, randomized, double blind study of the efficacy and safety of dutasteride and tamsulosin, alone or in combination, in men with moderate-to-severe benign prostatic hyperplasia. In this post-hoc investigation, we analyzed primary and secondary end-points from the Combination of Avodart and Tamsulosin study in Asian (n = 325) and Caucasian men (n = 4259). The incidence of acute urinary retention or benign prostatic hyperplasia-related surgery did not differ significantly between treatment groups in the Asian subpopulation. In Caucasian men, the incidence of acute urinary retention/benign prostatic hyperplasia-related surgery was significantly lower in the combination therapy group compared with the tamsulosin monotherapy group (P < 0.001), but not compared with dutasteride monotherapy. Combination therapy significantly increased the time to benign prostatic hyperplasia clinical progression and resulted in improved International Prostate Symptom Score, maximum urinary flow rate, quality of life, and reduced prostate volume in Asian and Caucasian men who received combination therapy compared with tamsulosin monotherapy. Combination therapy also significantly improved (P < 0.05) time to benign prostatic hyperplasia clinical progression, International Prostate Symptom Score, maximum urinary flow rate and quality of life versus dutasteride in the Caucasian subpopulation. The adverse-event profile was comparable between subpopulations. In conclusion, Asian and Caucasian men respond similarly to these treatments, despite apparent racial differences in 5alpha-reductase activity. PMID- 22774775 TI - Vaginal hysterectomy, an outpatient procedure. AB - OBJECTIVE: To report our experience of treating women undergoing vaginal hysterectomy in an outpatient setting and to identify risk factors for hospital admission and women dissatisfied with care. DESIGN: Prospective observational report. SETTING: department of obstetrics and gynecology, university hospital in Norway. SAMPLE: 150 women who underwent vaginal hysterectomy at the outpatient clinic from February 2009 to April 2010. METHODS: Perioperative data were collected prospectively and case notes were searched for complications. On the first postoperative day all women were contacted by telephone by a nurse. A visual analogue scale (VAS) was used to monitor pain and nausea during the stay at the outpatient clinic and the day after surgery. VAS was also used to specify the women's degree of satisfaction with care the day after surgery. MAIN OUTCOME MEASURE: The number of women who could be discharged from the outpatient unit and had a satisfaction score of >=7 the day after surgery. RESULTS: Of the 150 women, 84% could be discharged after a mean observation period of 276 min (SD +/- 80 min). The mean satisfaction score was 9.0, SD +/- 1.4, and 92.6% of the women reported >=7 points in the satisfaction score. No women with serious complications were sent home. Using a multivariable logistic regression model only pain at discharge was found as significant (p= 0.009) for admittance to hospital. CONCLUSIONS: Vaginal hysterectomy is a feasible outpatient procedure and the majority of women were satisfied with the care they received. PMID- 22774777 TI - Ultrastructural and enzymatic activity of membranous vesicles isolated from canine seminal plasma. AB - The objectives of this study were to verify the presence of membranous vesicles (MV) in canine seminal plasma by mean of transmission electron microscopy (TEM), to describe the ultrastructural characteristics and to identify some enzymatic activity associated with them. Semen samples, collected by digital manipulation from dogs with proven fertility, were pooled and used for membrane vesicles preparation according to conventional procedures. TEM observations showed the existence of vesicular membranous structures of more or less spherical shape with different sizes. These vesicles were surrounded by a single-, double- or multiple layered laminar membranes. The mean vesicle diameter was 117.6 +/- 86.9 nm ranging from 24.4 to 716.6 nm. Enzyme activity determinations showed the presence of adenosine deaminase, 5'-nucleotidase, ADPase, ATPase, dipeptilpeptidase IV, alkaline phosphatase, total acid phosphatase and prostatic acid phosphatase, while the aminopeptidase activity was absent. In conclusion, results of this study, compatible with results from other mammals, showed for the first time the presence of MV, their ultrastructural and enzymatic characteristics in dog seminal plasma. PMID- 22774776 TI - Evolution of gene expression and expression plasticity in long-term experimental populations of Drosophila melanogaster maintained under constant and variable ethanol stress. AB - Gene expression responds to the environment and can also evolve rapidly in response to altered selection regimes. Little is known, however, about the extent to which evolutionary adaptation to a particular type of stress involves changes in the within-generation ('plastic') responses of gene expression to the stress. We used microarrays to quantify gene expression plasticity in response to ethanol in laboratory populations of Drosophila melanogaster differing in their history of ethanol exposure. Two populations ('R' populations) were maintained on regular medium, two ('E') were maintained on medium supplemented with ethanol, and two ('M') were maintained in a mixed regime in which half of the population was reared on one medium type, and half on the other, each generation. After more than 300 generations, embryos from each population were collected and exposed to either ethanol or water as a control, and RNA was extracted from the larvae shortly after hatching. Nearly 2000 transcripts showed significant within generation responses to ethanol exposure. Evolutionary history also affected gene expression: the E and M populations were largely indistinguishable in expression, but differed significantly in expression from the R populations for over 100 transcripts, the majority of which did not show plastic responses. Notably, in no case was the interaction between selection regime and ethanol exposure significant after controlling for multiple comparisons, indicating that adaptation to ethanol in the E and M populations did not involve substantial changes in gene expression plasticity. The results give evidence that expression plasticity evolves considerably more slowly than mean expression. PMID- 22774778 TI - The atypical antipsychotic class of psychotropic agents. Foreword. PMID- 22774780 TI - A putative functional vomeronasal system in anuran tadpoles. AB - We investigated the occurrence and anatomy of the vomeronasal system (VNS) in tadpoles of 13 different anuran species. All of the species possessed a morphologically fully developed VNS with a highly conserved anatomical organisation. We found that a bean-shaped vomeronasal organ (VNO) developed early in the tadpoles, during the final embryonic stages, and was located in the anteromedial nasal region. Histology revealed the presence of bipolar chemosensory neurones in the VNO that were immunoreactive for the Galphao protein. Tract-tracing experiments demonstrated that chemosensory neurones from the VNO reach specific areas in the brain, where a discernible accessory olfactory bulb (AOB) could be observed. The AOB was located in the ventrolateral side of the anterior telencephalon, somewhat caudal to the main olfactory bulb. Synaptophysin-like immunodetection revealed that synaptic contacts between VNO and AOB are established during early larval stages. Moreover, using lectin staining, we identified glomerular structures in the AOB in most of the species that we examined. According to our findings, a significant maturation in the VNS is achieved in anuran larvae. Recent published evidence strongly suggests that the VNS appeared early in vertebrate evolution and was already present in the aquatic last common ancestor of lungfish and tetrapods. In this context, tadpoles may be a good model in which to investigate the anatomical, biochemical and functional aspects of the VNS in an aquatic environment. PMID- 22774781 TI - Measuring student engagement among elementary students: pilot of the Student Engagement Instrument--Elementary Version. AB - Early school withdrawal, commonly referred to as dropout, is associated with a plethora of negative outcomes for students, schools, and society. Student engagement, however, presents as a promising theoretical model and cornerstone of school completion interventions. The purpose of the present study was to validate the Student Engagement Instrument-Elementary Version (SEI-E). The psychometric properties of this measure were assessed based on the responses of an ethnically diverse sample of 1,943 students from an urban locale. Exploratory and confirmatory factor analyses indicated that the 4-factor model of student engagement provided the best fit for the current data, which is divergent from previous SEI studies suggesting 5- and 6-factor models. Discussion and implications of these findings are presented in the context of student engagement and dropout prevention. PMID- 22774782 TI - Longitudinal predictors of high school completion. AB - This longitudinal study examined predictors of dropout assessed in elementary school. Student demographic data, achievement, attendance, and ratings of behavior from the Behavior Assessment System for Children were used to predict dropout and completion. Two models, which varied on student sex and race, predicted dropout at rates ranging from 75% to 88%. Model A, which included the Behavioral Symptoms Index, School Problems composite, Iowa Tests of Basic Skills battery, and teacher ratings of student work habits, best predicted female and African American dropouts. Model B, which comprised the Adaptive Skills composite, the Externalizing composite, the School Problems composite, referral for a student support team meeting, and sex, was more accurate for predicting Caucasian dropouts. Both models demonstrated the same hit rates for predicting male dropouts. Recommendations for early warning indicators and linking predictors with interventions are discussed. PMID- 22774783 TI - Criterion-related validity of curriculum-based measurement in writing with narrative and expository prompts relative to passage copying speed in 10th grade students. AB - We investigated the criterion-related validity of four indicators of curriculum based measurement in writing (WCBM) when using expository versus narrative writing prompts as compared to the validity of passage copying speed. Specifically, we compared criterion-related validity of production-dependent (total words written, correct word sequences), accurate-production (correct minus incorrect word sequences [CIWS]), and production-independent (percent of correct word sequences [%CWS]) scoring methods on narrative and expository writing probes in relation to a state-mandated writing assessment. Participants included all tenth grade students (N=163) from a rural high school in the Midwest. Results indicated that the more complex indicators of writing, %CWS (when taking into account passage copying speed), and CIWS (when passage copying speed was not considered) on narrative probes explained the greatest amount of variance in the criterion measure. None of the WCBM indicators, alone or in combination with passage copying speed, explained more than 25% of the variance in the state writing assessment, suggesting that WCBM may have limitations as a universal screening measure for high school students. PMID- 22774784 TI - Perfectionism in gifted students: moderating effects of goal orientation and contingent self-worth. AB - We examined the moderating effects of mastery goals and academic contingency of self-worth (CSW-A) on how perfectionistic discrepancy associates with academic efficacy and satisfaction with life among gifted students in middle and high school. Participants in this study were 144 gifted students from 6th to 12th grade in a suburban Midwest U.S. school district. A significant three-way interaction effect was found among discrepancy, mastery goals, and CSW-A on academic self-efficacy. The findings suggest that having high mastery goals served as a protective factor against the negative impact of discrepancy on academic efficacy for gifted students, but only for those with low CSW-A. For gifted students with elevated CSW-A, discrepancy was not negatively associated with academic self-efficacy, regardless of their level of mastery goals. The implications for these findings are discussed. PMID- 22774785 TI - The association between sexual assault and suicidal activity in a national sample. AB - Sexual violence is a potential key risk factor for adolescent suicidal behavior but has not been studied extensively. Thus, the current study examined the extent to which sexual assault predicted suicide attempts among adolescent students in the national Youth Risk Behavior Surveillance System survey (2007 data). Gender differences in suicidal behavior overall and among sexual assault victims were examined. The results supported that students with sexual assault histories were significantly more likely (odds ratio [OR]=6.4) to have reported at least one suicide attempt in the past year than students who did not report sexual assault histories. Male students with a sexual assault history reported suicide attempts requiring medical attention more frequently than male attempters without sexual assault histories, as well as both groups of female suicide attempters. Implications of the findings for suicide prevention and intervention programs are discussed. PMID- 22774786 TI - The effectiveness of test-enhanced learning depends on trait test anxiety and working-memory capacity. AB - Despite being viewed as a better way to enhance learning than repeated study, it has not been clear whether repeated testing is equally effective for students with a wide range of cognitive abilities. The current study examined whether test enhanced learning would be equally beneficial to participants with varied working memory capacity (WMC) and trait test anxiety (TA). Chinese-English bilingual undergraduates in Hong Kong were recruited as participants. They acquired Swahili English word pairs (half via repeated study and half via repeated testing) and performed a delayed cued-recall test for all pairs about one week after the acquisition phase. Their WMC and TA were estimated by Unsworth, Heitz, Schrock, and Engle's (2005) operation-span task and the Chinese version of Spielberger's (1980) Test Anxiety Inventory, respectively. We replicated the typical testing effect: Participants performed better for pairs in the repeated-testing condition than those in the repeated-study condition. Regression analyses showed that, (a) relative to other participants, those with lower WMC and higher TA made more intralist intrusion errors (i.e., recalling a wrong English translation to a Swahili word cue) during the acquisition phase, and (b) the testing effect was negatively correlated with TA for participants with lower WMC, but was not correlated with TA for participants with higher WMC. This demonstrates a boundary condition for the use of test-enhanced learning. Implications of these findings for theories of the testing effect (e.g., Pyc & Rawson's, 2010, mediator effectiveness hypothesis) and their application in classroom settings are discussed. PMID- 22774787 TI - Can evolutionary principles explain patterns of family violence? AB - The article's aim is to evaluate the application of the evolutionary principles of kin selection, reproductive value, and resource holding power to the understanding of family violence. The principles are described in relation to specific predictions and the mechanisms underlying these. Predictions are evaluated for physical violence perpetrated by (a) parents to unrelated children, (b) parents to genetic offspring, and (c) offspring to parents and between (d) siblings and (e) sexual partners. Precise figures for risks have been calculated where possible. The major conclusions are that most of the evidence is consistent with evolutionary predictions derived from kin selection and reproductive value: There were (a) higher rates of violence to stepchildren, (b) a decline in violence with the age of offspring, and (c) an increase in violence with parental age, while (d) violence between siblings was generally at a low level and concerned resource disputes. The issue of distinguishing evolutionary from alternative explanations is addressed throughout and is problematic for predictions derived from reproductive value. The main evolutionary explanation for male partner violence, mate guarding as a result of paternity uncertainty, cannot explain Western studies where sex differences in control and violence between partners were absent, although other aspects of male partner violence are consistent with it, and it may explain sex differences in traditional cultures. Recurrent problems in evaluating the evidence were to control for possible confounds and thus to distinguish evolutionary from alternative explanations. Suggestions are outlined to address this and other issues arising from the review. PMID- 22774788 TI - Bayesian estimation supersedes the t test. AB - Bayesian estimation for 2 groups provides complete distributions of credible values for the effect size, group means and their difference, standard deviations and their difference, and the normality of the data. The method handles outliers. The decision rule can accept the null value (unlike traditional t tests) when certainty in the estimate is high (unlike Bayesian model comparison using Bayes factors). The method also yields precise estimates of statistical power for various research goals. The software and programs are free and run on Macintosh, Windows, and Linux platforms. PMID- 22774789 TI - Mere exposure to money increases endorsement of free-market systems and social inequality. AB - The present research tested whether incidental exposure to money affects people's endorsement of social systems that legitimize social inequality. We found that subtle reminders of the concept of money, relative to nonmoney concepts, led participants to endorse more strongly the existing social system in the United States in general (Experiment 1) and free-market capitalism in particular (Experiment 4), to assert more strongly that victims deserve their fate (Experiment 2), and to believe more strongly that socially advantaged groups should dominate socially disadvantaged groups (Experiment 3). We further found that reminders of money increased preference for a free-market system of organ transplants that benefited the wealthy at the expense of the poor even though this was not the prevailing system (Experiment 5) and that this effect was moderated by participants' nationality. These results demonstrate how merely thinking about money can influence beliefs about the social order and the extent to which people deserve their station in life. PMID- 22774790 TI - Exaggerated, mispredicted, and misplaced: when "it's the thought that counts" in gift exchanges. AB - Gift-giving involves both the objective value of a gift and the symbolic meaning of the exchange. The objective value is sometimes considered of secondary importance as when people claim, "It's the thought that counts." We evaluated when and how mental state inferences count in gift exchanges. Because considering another's thoughts requires motivation and deliberation, we predicted gift givers' thoughts would increase receivers' appreciation only when triggered to consider a giver's thoughts, such as when a friend gives a bad gift. Because gift givers do not experience this trigger, we expected they would mispredict when their thoughts count and when they do not. Three experiments support these predictions. A final experiment demonstrated that thoughts "count" for givers by increasing social connection to the receiver. These results suggest that mental state inferences are not automatic in social interactions and that inferences about how much thoughts count are systematically miscalibrated. PMID- 22774791 TI - The process of change in cognitive therapy for depression when combined with antidepressant medication: Predictors of early intersession symptom gains. AB - OBJECTIVE: Previous studies of cognitive therapy (CT) for depression have examined therapist adherence and the therapeutic alliance as predictors of subsequent symptom change. However, little is known about these CT process variables when CT is delivered in combination with antidepressant medication. METHOD: In a sample of 176 depressed outpatients randomized to the combined condition of a clinical trial, we examined ratings of adherence and alliance as predictors of subsequent session-to-session symptom change across early CT sessions. RESULTS: Both adherence to Behavioral Methods/Homework and the therapeutic alliance significantly predicted session-to-session symptom change. In models in which patients' medication regimen and prior symptom change were covaried, only Behavioral Methods/Homework remained a significant predictor of subsequent symptom change. CONCLUSIONS: Our findings highlight the utility of Behavioral Methods/Homework in combined treatment for promoting early session-to session symptom change. PMID- 22774793 TI - Ferdinando (Nando) Dianzani (1932-2012). PMID- 22774794 TI - Microencapsulation of alpha interferons in biodegradable microspheres. AB - The immunomodulatory, antiproliferative, and antiviral properties of interferons alpha (IFN-alpha) have made these cytokines attractive for numerous clinical applications. However, most of the current available IFN pharmaceutical dosage forms need to be injected frequently and may provoke adverse reactions in patients. This problem might be overcome by using biodegradable microspheres loaded with IFN. The encapsulation of IFN-alpha in microspheres and the current status of this technology are the main subjects reviewed here. To this end, we describe (i) the main methods and experimental parameters used to obtain IFN loaded microspheres and (ii) characterization of these microspheres in terms of morphology, particle size, loading/encapsulation efficiency, residual water content, residual solvent content, release profile, and sterility. Also, we discuss both the characterization of the encapsulated IFN and the stabilization/protection of IFN during microencapsulation. Finally, a brief overview of preclinical and clinical studies using IFN-containing microspheres is given. PMID- 22774792 TI - When diagnosing ADHD in young adults emphasize informant reports, DSM items, and impairment. AB - OBJECTIVE: This study examined several questions about the diagnosis of attention deficit/hyperactivity disorder (ADHD) in young adults using data from a childhood diagnosed sample of 200 individuals with ADHD (age M = 20.20 years) and 121 demographically similar non-ADHD controls (total N = 321). METHOD: We examined the use of self- versus informant ratings of current and childhood functioning and evaluated the diagnostic utility of adult-specific items versus items from the Diagnostic and Statistical Manual of Mental Disorders (DSM). RESULTS: Results indicated that although a majority of young adults with a childhood diagnosis of ADHD continued to experience elevated ADHD symptoms (75%) and clinically significant impairment (60%), only 9.6%-19.7% of the childhood ADHD group continued to meet DSM-IV-TR (DSM, 4th ed., text rev.) criteria for ADHD in young adulthood. Parent report was more diagnostically sensitive than self-report. Young adults with ADHD tended to underreport current symptoms, while young adults without ADHD tended to overreport symptoms. There was no significant incremental benefit beyond parent report alone to combining self-report with parent report. Non-DSM-based, adult-specific symptoms of ADHD were significantly correlated with functional impairment and endorsed at slightly higher rates than the DSM-IV-TR symptoms. However, DSM-IV-TR items tended to be more predictive of diagnostic group membership than the non-DSM adult-specific items due to elevated control group item endorsement. CONCLUSIONS: Implications for the assessment and treatment of ADHD in young adults are discussed (i.e., collecting informant reports, lowering the diagnostic threshold, emphasizing impairment, and cautiously interpreting retrospective reports). PMID- 22774798 TI - Perceptual grouping in haptic search: the influence of proximity, similarity, and good continuation. AB - We conducted a haptic search experiment to investigate the influence of the Gestalt principles of proximity, similarity, and good continuation. We expected faster search when the distractors could be grouped. We chose edges at different orientations as stimuli because they are processed similarly in the haptic and visual modality. We therefore expected the principles of similarity and good continuation to be operational in haptics as they are in vision. In contrast, because of differences in spatial processing between vision and haptics, we expected differences for the principle of proximity. In haptics, the Gestalt principle of proximity could operate at two distinct levels-somatotopic proximity or spatial proximity-and we assessed both possibilities in our experiments. The results show that the principles of similarity and good continuation indeed operate in this haptic search task. Neither of our proximity manipulations yielded effects, which may suggest that grouping by proximity must take place before an invariant representation of the object has formed. (PsycINFO Database Record (c) 2012 APA, all rights reserved). PMID- 22774796 TI - Mediators of antiretroviral adherence: a multisite international study. AB - The purpose of this study was to investigate the effects of stressful life events (SLE) on medication adherence (3 days, 30 days) as mediated by sense of coherence (SOC), self-compassion (SCS), and engagement with the healthcare provider (eHCP) and whether this differed by international site. Data were obtained from a cross sectional sample of 2082 HIV positive adults between September 2009 and January 2011 from sites in Canada, China, Namibia, Puerto Rico, Thailand, and US. Statistical tests to explore the effects of stressful life events on antiretroviral medication adherence included descriptive statistics, multivariate analysis of variance, analysis of variance with Bonferroni post-hoc analysis, and path analysis. An examination by international site of the relationships between SLE, SCS, SOC, and eHCP with adherence (3 days and 30 days) indicated these combined variables were related to adherence whether 3 days or 30 days to different degrees at the various sites. SLE, SCS, SOC, and eHCP were significant predictors of adherence past 3 days for the United States (p = < 0.001), Canada (p = 0.006), and Namibia (p = 0.019). The combined independent variables were significant predictors of adherence past 30 days only in the United States and Canada. Engagement with the provider was a significant correlate for antiretroviral adherence in most, but not all, of these countries. Thus, the importance of eHCP cannot be overstated. Nonetheless, our findings need to be accompanied by the caveat that research on variables of interest, while enriched by a sample obtained from international sites, may not have the same relationships in each country. PMID- 22774799 TI - Prediction during language processing is a piece of cake--but only for skilled producers. AB - Are there individual differences in children's prediction of upcoming linguistic input and what do these differences reflect? Using a variant of the preferential looking paradigm (Golinkoff, Hirsh-Pasek, Cauley, & Gordon, 1987), we found that, upon hearing a sentence like, "The boy eats a big cake," 2-year-olds fixate edible objects in a visual scene (a cake) soon after they hear the semantically constraining verb eats and prior to hearing the word cake. Importantly, children's prediction skills were significantly correlated with their productive vocabulary size-skilled producers (i.e., children with large production vocabularies) showed evidence of predicting upcoming linguistic input, while low producers did not. Furthermore, we found that children's prediction ability is tied specifically to their production skills and not to their comprehension skills. Prediction is really a piece of cake, but only for skilled producers. PMID- 22774800 TI - Acute coronary syndromes related to bio-climate in a Mediterranean area. The case of Ierapetra, Crete Island, Greece. AB - The occurrence of non-fatal acute coronary syndromes (ACS) is examined in relation with the local bioclimatic conditions in the Ierapetra area, in the southernmost part of Crete Island, Greece, during the period 2004-2007. Daily ACS counts and corresponding meteorological parameters, such as maximum and minimum air temperature, relative humidity, wind speed and cloudiness, were analyzed. Besides, the daily values of the human thermal index, physiologically equivalent temperature (PET) was evaluated. Pearson's chi(2) test and generalized linear models (GLM) with Poisson distribution were applied. The ACS syndromes present a multiple variation within the year, with the primary maximum in August and the secondary in May, while relative high ACS frequencies exist in early winter time. The impact of the weather variability on the ACS incidence is not statistically significant (C.L. 95%). PMID- 22774801 TI - Brain representations of negative numbers. AB - Participants performed a physical comparison task of pairs of positive and pairs of negative one-digit numbers while their electrophysiological brain activity was measured. The numerical value of the presented digits was either congruent or incongruent with the physical size of the digits. Analysis has shown that the earliest event-related potential (ERP) difference between positive and negative numbers was found in the P300 ERP component peak, where there was an inverse effect of congruity in the negative pairs, compared with the positive ones. This pattern of results supports the idea that natural numbers serve as primitives of the human cognitive system, whereas negative numbers are apparently generated if needed. PMID- 22774802 TI - Individual differences and emotional inferences during reading comprehension. AB - This study investigated readers' representations of the main protagonist's emotional status in short narratives, as well as several mental factors that may affect these representations. General and visuospatial working memory, empathy, and simulation were investigated as potential individual differences in generating emotional inferences. Participants were confronted with narratives conveying information about the protagonist's emotional state. We manipulated each narrative's target sentence according to its content (emotional label vs. description of the behaviour associated to the emotion) and its congruence to the story (matching vs. mismatching). The results showed that globally the difference between reading times of congruent and incongruent target sentences was bigger in the behavioural than in the emotional condition. This pattern was accentuated for high visuospatial working memory participants when they were asked to simulate the stories. These results support the idea that mental models may be of a perceptual nature and may more likely include behavioural elements than emotion labels per se, as suggested earlier by Gygax et al. (2007). PMID- 22774803 TI - Differential involvement of knowledge representation and executive control in episodic memory performance in young and older adults. AB - Craik and Bialystok (2006, 2008) postulated that examining the evolution of knowledge representation and control processes across the life span could help in understanding age-related cognitive changes. The present study explored the hypothesis that knowledge representation and control processes are differentially involved in the episodic memory performance of young and older adults. Young and older adults were administered a cued-recall task and tests of crystallized knowledge and executive functioning to measure representation and control processes, respectively. Results replicate the classic finding that executive and cued-recall performance decline with age, but crystallized-knowledge performance does not. Factor analysis confirmed the independence of representation and control. Correlation analyses showed that the memory performance of younger adults was correlated with representation but not with control measures, whereas the memory performance of older adults was correlated with both representation and control measures. Regression analyses indicated that the control factor was the main predictor of episodic-memory performance for older adults, with the representation factor adding an independent contribution, but the representation factor was the sole predictor for young adults. This finding supports the view that factors sustaining episodic memory vary from young adulthood to old age; representation was shown to be important throughout adulthood, and control was also important for older adults. The results also indicated that control and representation modulate age-group-related variance in episodic memory. PMID- 22774804 TI - An investigation of the time course of category congruence and priming distance effects in number classification tasks. AB - The issue investigated in the present research is the nature of the information that is responsible for producing masked priming effects (e.g., semantic information or stimulus-response [S-R] associations) when responding to number stimuli. This issue was addressed by assessing both the magnitude of the category congruence (priming) effect and the nature of the priming distance effect across trials using single-digit primes and targets. Participants made either magnitude (i.e., whether the number presented was larger or smaller than 5) or identification (i.e., press the left button if the number was either a 1, 2, 3, or 4 or the right button if the number was either a 6, 7, 8, or 9) judgments. The results indicated that, regardless of task instruction, there was a clear priming distance effect and a significantly increasing category congruence effect. These results indicated that both semantic activation and S-R associations play important roles in producing masked priming effects. PMID- 22774805 TI - Do kidney histology lesions predict long-term kidney function after liver transplantation? AB - Histological renal lesions observed after liver transplantation are complex, multifactorial, and interrelated. The aims of this study were to determine whether kidney lesions observed at five yr after liver transplantation can predict long-term kidney function. Ninety-nine liver transplant patients receiving calcineurin inhibitor (CNI)-based immunosuppression, who had undergone a kidney biopsy at 60+/-48 months post-transplant, were included in this follow up study. Kidney biopsies were scored according to the Banff classification. Estimated glomerular filtration rate (eGFR) was assessed at last follow-up, that is, 109+/-48 months after liver transplantation. eGFR decreased from 92+/-33 mL/min at transplantation to 63+/-19 mL/min after six months, to 57+/-17 mL/min at the kidney biopsy, to 54+/-24 mL/min at last follow-up (p<0.0001). At last follow-up, only three patients required renal replacement therapy. After the kidney biopsy, 13 patients were converted from CNIs to mammalian target of rapamycin inhibitors, but no significant improvement in eGFR was observed after conversion. Elevated eGFR at six months post-transplant and a lower fibrous intimal thickening score (cv) observed at five yr post-transplant were the two independent predictive factors for eGFR>=60 mL/min at nine yr post-transplant. Long-term kidney function seems to be predicted by the kidney vascular lesions. PMID- 22774840 TI - Shoaling as an antiparasite defence in minnows (Pimephales promelas) exposed to trematode cercariae. AB - 1. Individuals that live in groups benefit from increased foraging success and decreased predation. Protection from some types of parasites may provide an additional benefit of group-living. For fish, the extent to which shoaling can reduce an individual's risk of exposure to the infective stages of parasites is unknown. 2. We tested for antiparasite benefits of shoaling in fathead minnows exposed to larvae (cercariae) of two of their most common species of trematode, Ornithodiplostomum ptychocheilus and Posthodiplostomum minimum. As developing stages (metacercariae) of these trematodes cause reductions in minnow activity, growth and survival, natural selection should favour the evolution of cercariae avoidance behaviours. 3. We evaluated shoal dimensions in groups of minnows exposed to O. ptychocheilus and to other chemical/physical stimuli within aquaria. To compare risk of exposure in shoaling vs. non-shoaling fish, we confined groups of minnows into mesh cages in outdoor mesocosms, exposed them to cercariae, then compared mean worm numbers in grouped vs. solitary fish. Lastly, we tested whether fish located within the centre of an artificial shoal reduced their risk of cercariae exposure compared with those along peripheral edges. 4. Minnows distinguished infective cercariae from other potential aquatic threats and responded with activity that reduced the 2-dimensional area of their shoals 15-fold compared with water-only controls. Fish confined within artificial shoals had 3-fold fewer worms than single fish and minnows located within the centre of artificial shoals had significantly fewer worms than those without peripheral minnows. 5. These results show that shoaling reduces a minnows' risk of exposure to cercariae, either directly via detection of cercariae in the water column followed by behavioural avoidance or indirectly via behaviour-mediated differences in exposure between shoaling vs. non-shoaling fish. PMID- 22774807 TI - The new iminothiadiazole derivative VP1.14 ameliorates hippocampal damage after an excitotoxic injury. AB - Increased levels of glutamate causing excitotoxic damage accompany many neurological disorders. A well-characterized model of excitotoxic damage involves administration of kainic acid (KA), which causes limbic seizure activity and subsequent neuronal death, particularly in the CA1 and CA3 areas of the hippocampus. Inhibition of the enzyme glycogen synthase kinase-3 (GSK-3) and cAMP levels might play an important role in neuroprotection. As intracellular cAMP levels depend, in part, on the activity of the phosphodiesterase enzymes (PDEs), these enzymes have recently emerged as potential therapeutic targets for the treatment of several diseases. In previous works, we have shown a potent anti inflammatory and neuroprotective effect of GSK-3 inhibition in a model of excitotoxicity, as well as a reduction of nigrostriatal dopaminergic neuronal cell death after phosphodiesterase 7 inhibition, which leads to an increase in cAMP levels. This study was undertaken to determine whether simultaneous inhibition of GSK-3 and PDE-7 by a novel 5-imino-1,2,4-thiadiazole compound, named VP1.14, could prevent the massive neuronal loss in the hippocampus evoked by intrahippocampal injection of KA. Here, we show that rats treated with VP1.14 showed a reduced inflammatory response after KA injection, and exhibited a significant reduction in pyramidal cell loss in the CA1 and CA3 areas of the hippocampus. Studies with hippocampal HT22 cells in vitro also showed a clear neuroprotective effect of VP1.14 and an anti-inflammatory effect shown by a decrease in the nitrite liberation and in the expression of pro-inflammatory cytokines by primary cultures of astrocytes treated with lipopolysaccharide. PMID- 22774841 TI - Common local founder effects for Wilson's disease and hereditary hemochromatosis; mutation studies of a large family. AB - Wilson's disease (WND) and hereditary hemochromatosis (HH) are two metal loading diseases of copper and iron, respectively, and are both recessively inherited. In central Sweden, where HH is common, 9 Wilson kindred (14 members) were identified. Aims of the study were to test whether nine WND families shared a common origin, a common mutation and if carrying HFE mutations affected their phenotype. RESULTS: The nine families were traced through 13 generations to a common founder origin in the mid-seventeenth century. Despite identity of descent, four different ATP7B mutations appeared with homozygosity in four, with two different mutations, W779X and T977M. There were three compound heterozygotes, W779X/T977M, R1319X/H1069Q and one T977M combined with a new, previously not described mutation, probably of Finnish origin. The founder family also included 26 descendant kindred (55 members) with HH as shown by HFE mutations. This admixture coincided with a migration out of the original parish into hemochromatosis-rich localities. One WND patient had iron overload (serum ferritin 672 ug/l and raised liver enzymes), but lacked HFE mutations. In another family with serious hemochromatosis (two sons dying from bronze diabetes), the coinheritance of congenital spherocytosis was probably the cause rather than an additional effect of WND. CONCLUSIONS: WND though a rare disease may become aggregated like HH in certain areas due to local founder effects. Despite extensive pedigree studies leading back to the local founder family, the authors were unable to find a single defining mutation of the ATP7B gene. PMID- 22774842 TI - Validation of a brief stigma-by-association scale for use with HIV/AIDS-affected youth in South Africa. AB - This study validated a brief stigma-by-association scale for use with South African youth (adapted from the HIV Stigma-by-Association Scale for Adolescents). Participants were 723 youth (364 male, 359 female) from poor urban communities around Cape Town. Youths completed the brief stigma-by-association scale and measures of bullying victimisation and peer-problems, as well as inventories measuring symptoms of depression and anxiety. Exploratory analyses revealed that the scale consists of two subscales: (1) experience of stigma-by-association and (2) consequences of stigma-by-association. This two factor structure was obtained in the full sample and both the HIV/AIDS-affected and unaffected subgroups. The full stigma-by-association scale showed excellent reliability (alpha = 0.89-0.90) and reliabilities for both subscales were also good (alpha = 0.78-0.87). As predicted, children living in HIV/AIDS-affected households obtained significantly higher stigma-by-association scores than children in non-affected households [F(1, 693) = 46.53, p<0.001, partial eta(2)=0.06] and hypothesized correlations between stigma-by-association, bullying, peer problems, depression and anxiety symptoms were observed. It is concluded that the brief stigma-by-association scale is a reliable and valid instrument for use with South African youth; however, further confirmatory research regarding the structure of the scale is required. PMID- 22774843 TI - Real time monitoring of propofol blood concentration in ponies anaesthetized with propofol and ketamine. AB - This study examined the pharmacokinetics of propofol by infusion in ponies using an analyser for the rapid measurement of propofol concentrations. The analyser (Pelorus 1000; Sphere Medical Ltd., Cambridge, UK) has a measurement cycle of approximately five minutes. Ten Welsh-cross ponies (weighing 135-300 kg) undergoing minor procedures were studied after premedication with acepromazine 0.03 mg/kg and detomidine 0.015 mg/kg. Anaesthesia was induced with ketamine 2 mg/kg and diazepam 0.03 mg/kg, and maintained with an infusion of propofol at an initial rate of 0.16 mg/kg/min for the first thirty minutes, after a bolus of 0.3 mg/kg; and ketamine by infusion (20-40 MUg/kg/min). Blood samples (<2 mL) were collected prior to, during and after the infusion, and on assuming standing position. Anaesthesia was uneventful; with the duration of infusion 31-89 min. Blood propofol concentrations during the infusion ranged between 1.52 and 7.65 MUg/mL; pseudo-steady state concentrations 3.64-6.78 MUg/mL, and concentrations on assuming standing position 0.75-1.40 MUg/mL. Propofol clearance and volume of distribution were 31.4 (SD 6.1) mL/min/kg and 220.7 (132.0) mL/kg, respectively. The propofol analyser allows titration of propofol to a given concentration; and may be useful for anaesthesia in animals where kinetics are unknown; in disease states; and where intercurrent therapies affect propofol disposition. PMID- 22774845 TI - Structural and spectroscopic features of mixed valent Fe(II)Fe(I) complexes and factors related to the rotated configuration of diiron hydrogenase. AB - The compounds of this study have yielded to complementary structural, spectroscopic (Mossbauer, EPR/ENDOR, IR), and computational probes that illustrate the fine control of electronic and steric features that are involved in the two structural forms of (MU-SRS)[Fe(CO)2PMe3]2(0,+) complexes. The installation of bridgehead bulk in the -SCH2CR2CH2S- dithiolate (R = Me, Et) model complexes produces 6-membered FeS2C3 cyclohexane-type rings that produce substantial distortions in Fe(I)Fe(I) precursors. Both the innocent (Fc(+)) and the noninnocent or incipient (NO(+)/CO exchange) oxidations result in complexes with inequivalent iron centers in contrast to the Fe(I)Fe(I) derivatives. In the Fe(II)Fe(I) complexes of S = 1/2, there is complete inversion of one square pyramid relative to the other with strong super hyperfine coupling to one PMe3 and weak SHFC to the other. Remarkably, diamagnetic complexes deriving from isoelectronic replacement of CO by NO(+), {(MU-SRS)[Fe(CO)2PMe3] [Fe(CO)(NO)PMe3](+)}, are also rotated and exist in only one isomeric form with the -SCH2CR2CH2S- dithiolates, in contrast to R = H ( Olsen , M. T. ; Bruschi , M. ; De Gioia , L. ; Rauchfuss , T. B. ; Wilson , S. R. J. Am. Chem. Soc. 2008 , 130 , 12021 -12030 ). The results and redox levels determined from the extensive spectroscopic analyses have been corroborated by gas-phase DFT calculations, with the primary spin density either localized on the rotated iron in the case of the S = 1/2 compound, or delocalized over the {Fe(NO)} unit in the S = 0 complex. In the latter case, the nitrosyl has effectively shifted electron density from the Fe(I)Fe(I) bond, repositioning it onto the spin coupled Fe-N-O unit such that steric repulsion is sufficient to induce the rotated structure in the Fe(II) {Fe(I)((*)NO)}(8) derivatives. PMID- 22774846 TI - Higher glycosylated hemoglobin levels increase the risk of overactive bladder syndrome in patients with type 2 diabetes mellitus. AB - OBJECTIVES: To assess overactive bladder and its component symptoms among patients with type 2 diabetes mellitus and to explore whether higher glycosylated hemoglobin and other factors increase the risk of overactive bladder symptoms. METHODS: A total of 279 diabetes mellitus patients from our outpatient clinic, and 578 age- and sex-matched subjects without diabetes mellitus from public health centers were enrolled from May to September of 2010. The collected data included overactive bladder and its component symptoms measured by using the Overactive Bladder Symptom Score, and collecting demographic and clinical data. Overactive bladder was defined as total Overactive Bladder Symptom Score >=3 and urgency score >=2 (once a week or more). RESULTS: Diabetes mellitus patients had a significantly higher proportion of overactive bladder symptoms/urgency compared with the controls (28.0% vs 16.3%, odds ratio 2.03, 95% confidence interval 1.44 2.86), as well as nocturia (48.0% vs 39.1%, odds ratio 1.44, 95% confidence interval 1.08-1.93). There were no significant effects of diabetes mellitus on urge urinary incontinence (14.0% vs 10.9%, odds ratio 1.32, 95% confidence interval 0.86-2.04) and daytime frequency (26.9% vs 32.4%, odds ratio 0.77, 95% confidence interval 0.56-1.05). After adjusting for all variables, high glycosylated hemoglobin levels were significantly associated with overactive bladder/urgency (odds ratio 1.24, 95% confidence interval 1.06-1.45), urge urinary incontinence (odds ratio 1.20, 95% confidence interval 1.00-1.45) and nocturia (odds ratio 1.17, 95% confidence interval 1.01-1.35). CONCLUSIONS: Patients with type 2 mellitus present more overactive bladder symptoms/urgency and nocturia than controls. Among diabetic patients, higher glycosylated hemoglobin level represents an independent predictor of overactive bladder /urgency, urge urinary incontinence and nocturia. PMID- 22774844 TI - Contemporary cryptic sexuality in Trypanosoma cruzi. AB - Clonal propagation is considered to be the predominant mode of reproduction among many parasitic protozoa. However, this assumption may overlook unorthodox, infrequent or cryptic sexuality. Trypanosoma cruzi, which causes Chagas disease, is known to undergo non-Mendelian genetic exchange in the laboratory. In the field, evidence of extant genetic exchange is limited. In this study, we undertook intensive sampling of T. cruzi Discrete Typing Unit I in endemic eastern Colombia. Using Fluorescence-activated cell sorting, we generated 269 biological clones from 67 strains. Each clone was genotyped across 24 microsatellite loci. Subsequently, 100 representative clones were typed using 10 mitochondrial sequence targets (3.76 Kbp total). Clonal diversity among humans, reservoir hosts and vectors suggested complex patterns of superinfection and/or coinfection in oral and vector-borne Chagas disease cases. Clonal diversity between mother and foetus in a congenital case demonstrates that domestic TcI genotypes are infective in utero. Importantly, gross incongruence between nuclear and mitochondrial markers is strong evidence for widespread genetic exchange throughout the data set. Furthermore, a confirmed mosaic maxicircle sequence suggests intermolecular recombination between individuals as a further mechanism of genetic reassortment. Finally, robust dating based on mitochondrial DNA indicates that the emergence of a widespread domestic TcI clade that we now name TcI(DOM) (formerly TcIa/VEN(Dom)) occurred 23 000 +/- 12 000 years ago and was followed by population expansion, broadly corresponding with the earliest human migration into the Americas. PMID- 22774847 TI - Validation of MALDI-TOF MS for rapid classification and identification of lactic acid bacteria, with a focus on isolates from traditional fermented foods in Northern Vietnam. AB - AIMS: To evaluate the potential use of MALDI-TOF MS for fast and reliable classification and identification of lactic acid bacteria (LAB) from traditional fermented foods. METHODS AND RESULTS: A total of 119 strains of LAB from fermented meat (nem chua) were analysed with both (GTG)(5)-PCR fingerprinting and MALDI-TOF MS. Cluster analysis of the profiles revealed five species represented by a single isolate both in (GTG)(5)-PCR and in MALDI-TOF MS; five species grouped alike for (GTG)(5)-PCR and for MALDI-TOF MS; however, differences in minimal similarity between the delineated (GTG)(5)-PCR and MALDI-TOF MS clusters could be observed; three species showed more heterogeneity in their MALDI-TOF MS profiles compared to their (GTG)(5)-PCR profiles; two species, each represented by a single MALDI-TOF cluster, were subdivided in the corresponding (GTG)(5)-PCR dendrogram. As proof of the identification potential of MALDI-TOF MS, LAB diversity from one fermented mustard sample was analysed using MALDI-TOF MS. PheS gene sequencing was used for validation. CONCLUSIONS: MALDI-TOF MS is a powerful, fast, reliable and cost-effective technique for the identification of LAB associated with the production of fermented foods. SIGNIFICANCE AND IMPACT OF THE STUDY: Food LAB can be identified using MALDI-TOF MS, and its application could possibly be extended to other food matrices and/or other food-derived micro organisms. PMID- 22774849 TI - Fungal food choices of Dermatophagoides farinae affect indoor fungi selection and dispersal. AB - House dust mite (HDM) feces and molds are the main allergens involved in allergic asthma. Differences exist between the housing fungal biome of allergic patients and standard or unhealthy housing. House dust mite (HDM) feed off spores and transport them on their bodies, but do they have fungal food preferences? We observed Dermatophagoides farinae in vitro with 16 mold menus and repeated the experiment 10 times. This observation led us to define Alternaria alternata, Cladosporium sphaerospermum, and Wallemia sebi as "tasty" molds and Penicillium chrysogenum, Aspergillus versicolor, and Stachybotrys chartarum as "repulsive" molds. The food preferences of D. farinae may play a role in the following two phenomena: a decrease in spore numbers due to HDM consumption and a scattering of spores that stick to the bodies of HDMs. The extent of these two phenomena should be estimated in future studies for other common domestic HDM species. PMID- 22774850 TI - The role of rehearsal on the output order of immediate free recall of short and long lists. AB - Participants tend to initiate immediate free recall (IFR) of short lists of words with the very first word on the list. Three experiments examined whether rehearsal is necessary for this recent finding. In Experiment 1, participants were presented with lists of between 2 and 12 words for IFR at a fast, medium, or slow rate, with and without articulatory suppression (AS). The tendency to initiate output with the first item for short lists (a) did not change greatly when presentation rate was increased from a medium to a fast rate under normal conditions, (b) was reduced but not eliminated by AS, and (c) was maintained at slower rates when rehearsal was allowed but decreased at slower rates when rehearsal was prevented. In Experiment 2, the overt rehearsal methodology was used, and the tendency to initiate output with the first item for short lists was present even in the absence of overt rehearsal. Experiment 3 re-examined IFR under normal encoding conditions and replicated the main findings from the normal encoding conditions of Experiment 1 while using the presentation rates and list lengths of Experiment 2. We argue that rehearsal is not strictly necessary for the tendency to initiate recall with the first item under normal conditions, but rehearsal nevertheless contributes to this effect at slower rates. PMID- 22774851 TI - Dissociative contributions of semantic and lexical-phonological information to immediate recognition. AB - Several neuropsychological studies have reported that patients with memory deficits exhibit a dissociation of effects attributed to semantic and lexical phonological information in verbal working memory (e.g., Reilly, Martin, & Grossman, 2005; Romani & Martin, 1999). The present study reports on 3 experiments conducted with individuals without memory problems to examine the dissociation between the word imageability effect (WIE) and the word frequency effect (WFE). Experiment 1 used a modified semantic recognition task, in which participants were presented with 10-item lists and selected synonyms of list words from among 5 words. This task led to a significant WIE but no WFE. On the other hand, Experiment 2 used a modified recognition task in which targets were homophones, to promote the usage of phonological information while minimizing the potential impact of semantic information. There was no WIE but a significant WFE in Experiment 2. Experiment 3 replicated the results of Experiment 1 using 5-item lists and a 2-alternative forced choice procedure. Taken together, these results systematically replicate the double dissociation observed in neuropsychological studies. These findings suggest that semantic information can contribute to successful retrieval from verbal working memory without mediation from lexical phonological information. PMID- 22774853 TI - Prosodic boundaries delay the processing of upcoming lexical information during silent sentence reading. AB - Prosodic boundaries can be used to guide syntactic parsing in both spoken and written sentence comprehension, but it is unknown whether the processing of prosodic boundaries affects the processing of upcoming lexical information. In 3 eye-tracking experiments, participants read silently sentences that allow for 2 possible syntactic interpretations when there is no comma or other cue specifying which interpretation should be taken. In Experiments 1 and 2, participants heard a low-pass filtered auditory version of the sentence, which provided a prosodic boundary cue prior to each sentence. In Experiment 1, we found that the boundary cue helped syntactic disambiguation after the cue and led to longer fixation durations on regions right before the cue than on identical regions without prosodic boundary information. In Experiments 2 and 3, we used a gaze-contingent display-change paradigm to manipulate the parafoveal visibility of the first constituent character of the target word after the disambiguating position. Results of Experiment 2 showed that previewing the first character significantly reduced the reading time of the target word, but this preview benefit was greatly reduced when the prosodic boundary cue was introduced at this position. In Experiment 3, instead of the acoustic cues, a visually presented comma was inserted at the disambiguating position in each sentence. Results showed that the comma effect on lexical processing was essentially the same as the effect of prosodic boundary cue. These findings demonstrate that processing a prosodic boundary could impair the processing of parafoveal information during sentence reading. PMID- 22774852 TI - Test-potentiated learning: distinguishing between direct and indirect effects of tests. AB - The facilitative effect of retrieval practice, or testing, on the probability of later retrieval has been the focus of much recent empirical research. A lesser known benefit of retrieval practice is that it may also enhance the ability of a learner to benefit from a subsequent restudy opportunity. This facilitative effect of retrieval practice on subsequent encoding is known as test-potentiated learning. Thus far, however, the literature has not isolated the indirect effect of retrieval practice on subsequent memory (via enhancing the effectiveness of restudy) from the direct effects of retrieval on subsequent memory. The experiment presented here uses conditional probability to disentangle test potentiated learning from the direct effects of retrieval practice. The results indicate that unsuccessful retrieval attempts enhance the effectiveness of subsequent restudy, demonstrating that tests do potentiate subsequent learning. PMID- 22774848 TI - CD47 update: a multifaceted actor in the tumour microenvironment of potential therapeutic interest. AB - CD47 is a ubiquitous 50 kDa five-spanning membrane receptor that belongs to the immunoglobulin superfamily. This receptor, also known as integrin-associated protein, mediates cell-to-cell communication by ligation to transmembrane signal regulatory proteins SIRPalpha and SIRPgamma and interacts with integrins. CD47 is also implicated in cell-extracellular matrix interactions via ligation with thrombospondins. Furthermore, CD47 is involved in many and diverse cellular processes, including apoptosis, proliferation, adhesion and migration. It also plays a key role in many immune and cardiovascular responses. Thus, this multifaceted receptor might be a central actor in the tumour microenvironment. Solid tumours are composed of not only cancer cells that actively proliferate but also other cell types including immune cells and fibroblasts that make up the tumour microenvironment. Tumour cell proliferation is strongly sustained by continuous sprouting of new vessels, which also represents a gate for metastasis. Moreover, infiltration of inflammatory cells is observed in most neoplasms. Much evidence has accumulated indicating that infiltrating leukocytes promote cancer progression. Given its ubiquitous expression on all the different cell types that compose the tumour microenvironment, targeting CD47 could represent an original therapeutic strategy in the field of oncology. We present a current overview of the biological effects associated with CD47 on cancer cells and stromal cells. PMID- 22774854 TI - Lexical integration of novel words without sleep. AB - Learning a new word involves integration with existing lexical knowledge. Previous work has shown that sleep-associated memory consolidation processes are important for the engagement of novel items in lexical competition. In 3 experiments we used spaced exposure regimes to investigate memory for novel words and whether lexical integration can occur within a single day. The degree to which a new spoken word (e.g., cathedruke) engaged in lexical competition with established phonological neighbors (e.g., cathedral) was employed as a marker for lexical integration. We found evidence for improvements in recognition and cued recall following a time period including sleep, but we also found lexical competition effects emerging within a single day. Spaced exposure to novel words on its own did not bring about this within-day lexical competition effect (Experiment 2), which instead occurred with either spaced or massed exposure to novel words, provided that there was also spaced exposure to the phonological neighbors (Experiments 1 and 3). Although previous studies have indicated that sleep-dependent memory consolidation may be sufficient for lexical integration, our results show it is not a necessary precondition. PMID- 22774855 TI - Pitfall or scaffolding? Starting-point pull in configuration tasks. AB - In configuration problems, such as the construction of a weekly study schedule, decision makers must assemble a combination of parts under a set of constraints. Interactions may be present between the parts, and more than a single objective function may exist, such as minimizing the number of days on campus and maximizing the interest level of the courses. Little is known about the decision making processes involved in configuration tasks. Building on problem-solving and resource-allocation literature, the current study examines the effect of the starting points on performance in these tasks. We predicted that task constraints serve as starting points for the construction process that pull the entire configuration toward them. In 2 experiments, we asked participants to construct a weekly course schedule. We manipulated the course-offering sets so that starting the configuration with one of the task constraints (mandatory courses or a requirement to be on campus on specific days) and myopically building the configuration around it would either help or hinder the effort to reach a good schedule. By several convergent measures, participants succeeded more with the "Asset" course-offering sets than with the "Obstacle" sets. Think-aloud protocol analysis also supported this starting-point pull effect. The results of Experiment 3 show that for a starting point to pull the configuration, it has to be a constraint on the task. All 3 experiments show how building the configuration myopically around the starting points unduly affects the end result. PMID- 22774856 TI - Modulation of additive and interactive effects in lexical decision by trial history. AB - Additive and interactive effects of word frequency, stimulus quality, and semantic priming have been used to test theoretical claims about the cognitive architecture of word-reading processes. Additive effects among these factors have been taken as evidence for discrete-stage models of word reading. We present evidence from linear mixed-model analyses applied to 2 lexical decision experiments indicating that apparent additive effects can be the product of aggregating over- and underadditive interaction effects that are modulated by recent trial history, particularly the lexical status and stimulus quality of the previous trial's target. Even a simple practice effect expressed as improved response speed across trials was powerfully modulated by the nature of the previous target item. These results suggest that additivity and interaction between factors may reflect trial-to-trial variation in stimulus representations and decision processes rather than fundamental differences in processing architecture. PMID- 22774857 TI - Trend damping: Under-adjustment, experimental artifact, or adaptation to features of the natural environment? AB - People's forecasts from time series underestimate future values for upward trends and overestimate them for downward ones. This trend damping may occur because (a) people anchor on the last data point and make insufficient adjustment to take the trend into account, (b) they adjust toward the average of the trends they have encountered within the experiment, or (c) they are adapted to an environment in which natural trends tend to be damped. Two experiments eliminated the first account: For series that are negatively accelerated or have shallow slopes, people showed anti-damping (the opposite of damping), a phenomenon that cannot be interpreted in terms of under-adjustment. These experiments also produced results consistent with the second account: Forecasts for a given function clearly depended on the other functions that were forecast within the same experiment. However, this second account was itself eliminated by a third experiment demonstrating both damping and, to a lesser degree, anti-damping when people forecast from a single series. We conclude that people have adapted to degrees of growth and decay that are representative of their environment: Damping occurs when trends in presented series are steeper than this and anti-damping occurs when they are shallower. PMID- 22774858 TI - Working memory capacity and Stroop interference: global versus local indices of executive control. AB - Two experiments examined the relations among working memory capacity (WMC), congruency-sequence effects, proportion-congruency effects, and the color-word Stroop effect to test whether congruency-sequence effects might inform theoretical claims regarding WMC's prediction of Stroop interference. In Experiment 1, subjects completed either a high-congruency or low-congruency Stroop task that restricted trial-to-trial repetitions of stimulus dimensions to examine WMC's relation to congruency-sequence effects while minimizing bottom-up, stimulus-driven contributions. Congruency-sequence effects and congruency proportion effects were significant but did not interact. WMC predicted global Stroop interference under low-congruency conditions but neither local congruency sequence effects nor global Stroop interference under high-congruency conditions, contrary to previous studies (e.g., Kane & Engle, 2003). A high-congruency Stroop task in Experiment 2 removed the Experiment 1 task constraints, and, here, we obtained the typical, global association between WMC and Stroop interference but still no relation between WMC and congruency-sequence effects. We thus examined the methodological differences between Experiments 1 and 2 to determine whether any of these were locally responsible for the global WMC-related differences. They were not, suggesting that the changes between Experiments 1 and 2 created a general task context that engaged (or disengaged) the executive processes associated with WMC. PMID- 22774859 TI - Predictive value of ultrasound assessed fetal head position in primiparous women with prolonged first stage of labor. AB - OBJECTIVE: To examine how well ultrasound-assessed occipitoposterior (OP) position or high sagittal (HS) position in primiparous women with a prolonged first stage of labor predicts a vaginal delivery and the duration of labor. DESIGN: Prospective observational study. SETTING: Stavanger University Hospital, a secondary referral center in Norway. POPULATION: 105 primiparous women with prolonged first stage of labor. METHODS: Ultrasound assessment of fetal head position. Main outcome measures. Vaginal delivery vs. cesarean section and duration of labor. RESULTS: Twenty-five fetuses (24%) were delivered with cesarean section (CS), 45 (43%) had an operative vaginal delivery and 35 (33%) delivered spontaneously. Eleven (27%) of 41 fetuses in OP position at the time of inclusion were born in OP position. Ten (24%) of the 41 fetuses in OP position at inclusion were delivered with CS compared with 15/64 (23%) fetuses in other positions (p= 0.91). Twenty-eight fetuses were in sagittal position and 12 in HS position, assessed with ultrasound at the time of diagnosed prolonged labor. Seven (58%) of 12 in HS position delivered vaginally and five (42%) had a CS (p= 0.89). Time from inclusion to labor was not significant longer either for fetuses in OP compared with non-OP positions or for fetuses in HS compared with non-HS positions. CONCLUSIONS: Most fetuses in OP or HS positions in the first stage of labor will rotate spontaneously and have a high probability of being delivered vaginally. PMID- 22774860 TI - Nanoparticle surface charge mediates the cellular receptors used by protein nanoparticle complexes. AB - Nanoparticles are increasingly important for biological applications ranging from drug delivery to cellular imaging. In the course of these applications, nanoparticles are exposed to a complex environment of extracellular proteins that can be adsorbed onto the surface of the nanoparticle, altering nanoparticle-cell interactions. We have investigated how proteins found in blood serum affect the binding of nanoparticles to the surface of cells. Using fluorescence microscopy, we find that the cellular binding of cationic nanoparticles is enhanced by the presence of serum proteins, while the binding of anionic nanoparticles is inhibited. We have determined that this difference in cellular binding is due to the use of distinct cellular receptors. Competition assays, quantified with flow cytometry, show that the protein-nanoparticle complex formed from the cationic nanoparticles binds to scavenger receptors on the cell surface. Interestingly, the protein-nanoparticle complex formed from anionic nanoparticles binds to native protein receptors. As nanoparticles become increasingly important for in vivo applications, we expect these results will inform the design of nanoparticles with improved cellular binding. PMID- 22774861 TI - Palladium-catalyzed borylation of primary alkyl bromides. AB - A mild Pd-catalyzed process for the borylation of alkyl bromides has been developed using bis(pinacolato)diboron as a boron source. This process accommodates the use of a wide range of functional groups on the alkyl bromide substrate. Primary bromides react with complete selectivity in the presence of a secondary bromide. The generality of this approach is demonstrated by its extension to the use of alkyl iodides and alkyl tosylates, as well as borylation reactions employing bis(neopentyl glycolato)diboron as the boron source. PMID- 22774862 TI - Significant impact of recurrent respiratory tract infections in children with Down syndrome. AB - OBJECTIVE: Parents and health professionals believe that recurrent respiratory tract infections (RRTI) have a large impact on children with Down syndrome (DS). We studied the relation between parent-reported RRTI and development, behaviour and health-related quality of life (HRQoL) in 8-year-old children with DS. METHOD: During a 3-year period, 325 children with DS were recruited for inclusion in this observational study. Parents were asked to fill in the Child Behavior Checklist and TNO-AZL Children's Quality of Life Parent Form. A psychological assistant administrated the McCarthy Scales of Children's Abilities. The children were divided into a group with presence of RRTI (RRTI (+) ) and a group without RRTI (RRTI (-) ), on the basis of parental report. Linear regression analyses were performed to assess the effect of RRTI, while correcting for the influence of confounders. RESULTS: Compared with RRTI (-) children (n = 176), RRTI (+) children (n = 149, 46%) showed decreased mental and motor development (mean developmental age 3.67 vs. 4.08 years), more behavioural problems and lower scores on most HRQoL scales (P < 0.05). Moreover, school enrolment is less favourable in RRTI (+) children. CONCLUSION: In 8-year-olds with DS, the children with parent-reported RRTI show more delayed development, more behavioural problems and lower HRQoL compared with the children without RRTI. Although this association does not prove a causal relationship, further studies should focus on this, because RRTI are potentially preventable. PMID- 22774863 TI - A role for reactive oxygen species in the antibacterial properties of carbon monoxide-releasing molecules. AB - Carbon monoxide-releasing molecules (CO-RMs) are, in general, transition metal carbonyl complexes that liberate controlled amounts of CO. In animal models, CO RMs have been shown to reduce myocardial ischaemia, inflammation and vascular dysfunction, and to provide a protective effect in organ transplantation. Moreover, CO-RMs are bactericides that kill both Gram-positive and Gram-negative bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. Herein are reviewed the microbial genetic and biochemical responses associated with CO-RM mediated cell death. Particular emphasis is given to the data revealing that CO RMs induce the generation of reactive oxygen species (ROS), which contribute to the antibacterial activity of these compounds. PMID- 22774865 TI - Relationships among client and counselor agreement about the working alliance, session evaluations, and change in client symptoms using response surface analysis. AB - Two studies explored how counselor and client agreement on the therapy alliance, at the beginning of treatment, influenced early session evaluations and symptom change. Unlike prior studies that operationalized alliance convergence as either a profile similarity correlation or a difference score, the present study used polynomial regression and response surface analysis to examine agreement. Study 1 explored the impact of working alliance congruence on session depth and smoothness at the 3rd session of treatment with 36 client-counselor dyads. Results revealed that session smoothness was greater when clients' and therapists' perceptions of the working alliance were in agreement and high compared with when they were in agreement and low. In addition, clients rated sessions less smooth when their ratings of the alliance were lower than their therapists' ratings of the alliance, and they rated sessions as more smooth when their ratings of the alliance were higher than their therapists' ratings of the alliance. The authors did not find a significant relationship with session depth. In Study 2, the authors explored the impact of working alliance congruence, at the 3rd session of therapy, on symptom change for 63 client-counselor dyads. Results revealed that as the therapist and client have more positive agreement on the perceived alliance at the beginning of the treatment, there is greater symptom change. The authors also found that the consequences of alliance disagreement are the same regardless of who rated the alliance higher than the other. Implications and recommendations for future research are discussed. PMID- 22774864 TI - Differences in phosphorylation patterns of intracellular signaling proteins in T cells from kidney transplant patients with different outcomes. AB - Transplant patients with long-term graft survival (LTS) may have developed mechanisms that prevent rejection and allow graft function under low or no immunosuppressive therapy. In murine models, T cell tolerance is associated with alterations in the expression/activation of proteins involved in T cell signaling. These alterations have not been reported in transplanted patients with different outcomes. This study aimed to evaluate calcium mobilization, the phosphorylation of different proteins involved in T cell signaling and the expression of molecules associated with anergy, in T cells from kidney transplant patients. No differences were observed in calcium mobilization, although transplanted patients had a tendency toward augmented calcium flux. Chronic rejection patients (ChrRx) displayed lower Lck basal phosphorylation levels compared with LTS patients, and the phosphorylation profile of proteins evaluated was different. Among the groups, phosphorylation of Zap-70 was higher in LTS patients compared with ChrRx, and LAT phosphorylation was lower in LTS and ChrRx patients compared with healthy controls. The expression of molecules related to the anergic phenotype was similar among the study groups. Results suggest that phosphorylation patterns, rather than phosphorylation levels, may correlate with transplant outcome and that anergy may not be the main mechanism mediating LTS. PMID- 22774866 TI - The meaning of work among Chinese university students: findings from prototype research methodology. AB - This study examined Chinese university students' conceptualization of the meaning of work. One hundred and ninety students (93 male, 97 female) from Beijing, China, participated in the study. Prototype research methodology (J. Li, 2001) was used to explore the meaning of work and the associations among the identified meanings. Cluster analysis was used to organize the identified meanings into a structure consisting of lateral and hierarchical levels. The themes that emerged fell into 2 large categories named "ideal" and "reality." A series of superordinate-level and basic-level prototypes were found under each of these 2 categories. These prototypes reflected influences from both Chinese traditional and Western value orientations, as well as perceptions that are to be understood in the contemporary social and economic contexts of China. Implications for career development theory, research, and practice are discussed. PMID- 22774867 TI - Advisory working alliance, perceived English proficiency, and acculturative stress. AB - The aim of this study was to examine the moderators of (a) general or cross cultural advisory working alliances and (b) perceived English proficiency on the association between acculturative stress and psychological distress. A total of 143 East Asian international students completed an online survey. Results from a hierarchical regression indicated significant three-way interactions of (a) General Advisory Working Alliances * Perceived English Proficiency * Acculturative Stress on Psychological Distress and (b) Cross-Cultural Advisory Working Alliances * Perceived English Proficiency * Acculturative Stress on Psychological Distress. Specifically, the present results indicated that acculturative stress was significantly associated with psychological distress only when students perceived lower English proficiency and had a stronger general or cross-cultural advisory working alliance. However, acculturative stress was not significantly related to psychological distress when these students perceived lower English proficiency and had a weaker advisory working alliance (i.e., general or cross-cultural). In addition, acculturative stress was also not significantly related to psychological distress when these students perceived higher English proficiency and had a stronger or weaker advisory working alliance (i.e., general or cross-cultural). PMID- 22774868 TI - "HIV testing is so gay": the role of masculine gender role conformity in HIV testing among men who have sex with men. AB - Men who have sex with men (MSM) account for more than half of all new cases of HIV infection in the United States. Yet, many MSM are unaware of their HIV serostatus. Consistent with research indicating that gender role conformity impacts health behaviors, this study examined how masculine norms may influence HIV testing among MSM in the United States. Data from 170 self-identified MSM (age M = 46.45, SD = 12.18) of self-reported negative or unknown HIV serostatus living in the United States were used in this study. About half (52%) of participants reported that they had been tested for HIV within the past 12 months; 48% reported that they had not. Logistic regression was used to examine the association between domains of masculine gender role conformity and HIV testing within the past 12 months, controlling for number of sexual partners in the last 12 months. The masculine norm of heterosexual self-presentation (i.e., desire to be perceived by others as heterosexual) was negatively associated with HIV testing (B = -0.74, SE B = 0.36, O.R. = 0.48, 95% CI [0.24, 0.96]), after controlling for the effect of number of sexual partners. Psychologists and other health professionals may remain mindful of potential implications of HIV testing among MSM, including potential for MSM to view HIV testing as an "outing" procedure. PMID- 22774869 TI - Bibliotherapy for low sexual desire: evidence for effectiveness. AB - This study examines the effectiveness of bibliotherapy for low sexual desire among women, which is the most frequent sexual concern brought to counselors. Forty-five women responded to an advertisement for participation in a study on low sexual desire and were assigned to either the intervention or the wait-list control group. The intervention group completed the Hurlbert Index of Sexual Desire (HISD; Apt & Hurlbert, 1992) and the Female Sexual Function Index (FSFI; R. Rosen et al., 2000), read the self-help book under study in 6 weeks, and completed the measures a second time. The control group completed the same measures 6 weeks apart. Results demonstrated that the intervention group made statistically greater gains over time as compared with the control group on measures of sexual desire (HISD and FSFI Desire subscale), sexual arousal (FSFI Arousal subscale), sexual satisfaction (FSFI Satisfaction subscale), and overall sexual functioning (FSFI Total Score). A subset of participants in the intervention group participated in a 7-week follow-up study, and these participants maintained their gains in sexual desire and overall sexual functioning. Findings have important implications for future research on the efficacy of bibliotherapy generally and for low sexual desire specifically. Results also have vital implications for the treatment of low sexual desire. PMID- 22774870 TI - Callings and work engagement: moderated mediation model of work meaningfulness, occupational identity, and occupational self-efficacy. AB - Scholarly interest in callings is growing, but researchers' understanding of how and when callings relate to career outcomes is incomplete. The present study investigated the possibility that the relationship of calling to work engagement is mediated by work meaningfulness, occupational identity, and occupational self efficacy--and that this mediation depends on the degree of perceived person-job fit. I examined a highly educated sample of German employees (N = 529) in diverse occupations and found support for 2 of the 3 hypothesized mediators-work meaningfulness and occupational identity--after controlling for the relation of core self-evaluations to work engagement. Contrary to expectations, the mediated relations of callings to work engagement were not conditional upon the degree of person--job fit. The findings are considered in terms of the pathways through which callings may relate to work engagement and other career development outcomes. PMID- 22774871 TI - Ethnic and mainstream social connectedness, perceived racial discrimination, and posttraumatic stress symptoms. AB - Carter (2007) proposed the notion of race-based traumatic stress and argued that experiences of racial discrimination can be viewed as a type of trauma. In a sample of 383 Chinese international students at 2 predominantly White midwestern universities, the present results supported this notion and found that perceived racial discrimination predicted posttraumatic stress symptoms over and above perceived general stress. Furthermore, Berry (1997) proposed an acculturation framework and recommended that researchers advance the literature by examining the moderation effects on the association between racial discrimination and outcomes. The present results supported the moderation effect for Ethnic SC (i.e., social connectedness in the ethnic community), but not for Mainstream SC (i.e., social connectedness in mainstream society). A simple effects analysis indicated that a high Ethnic SC weakened the strength of the association between perceived racial discrimination and posttraumatic stress symptoms more than a low Ethnic SC. Moreover, although Mainstream SC failed to be a moderator, Mainstream SC was significantly associated with less perceived general stress, less perceived racial discrimination, and less posttraumatic stress symptoms. PMID- 22774872 TI - Molecular basis for the differential sensitivity of rat and human alpha9alpha10 nAChRs to alpha-conotoxin RgIA. AB - The alpha9alpha10 nicotinic acetylcholine receptor (nAChR) may be a potential target in pathophysiology of the auditory system, chronic pain, and breast and lung cancers. Alpha-conotoxins, from the predatory marine snail Conus, are potent nicotinic antagonists, some of which are selective for the alpha9alpha10 nAChR. Here, we report a two order of magnitude species difference in the potency of alpha-conotoxin RgIA for the rat versus human alpha9alpha10 nAChR. We investigated the molecular mechanism of this difference. Heterologous expression of the rat alpha9 with the human alpha10 subunit in Xenopus oocytes resulted in a receptor that was blocked by RgIA with potency similar to that of the rat alpha9alpha10 nAChR. Conversely, expression of the human alpha9 with that of the rat alpha10 subunit resulted in a receptor that was blocked by RgIA with potency approaching that of the human alpha9alpha10 receptor. Systematic substitution of residues found in the human alpha9 subunit into the homologous position in the rat alpha9 subunit revealed that a single point mutation, Thr56 to Ile56, primarily accounts for this species difference. Remarkably, although the alpha9 nAChR subunit has previously been reported to provide the principal (+) binding face for binding of RgIA, Thr56 is located in the (-) complementary binding face. PMID- 22774873 TI - Photodynamic inactivation of planktonic cultures and biofilms of Candida albicans mediated by aluminum-chloride-phthalocyanine entrapped in nanoemulsions. AB - New drug delivery systems, such as nanoemulsions (NE), have been developed to allow the use of hydrophobic drugs on the antimicrobial photodynamic therapy. This study evaluated the photodynamic potential of aluminum-chloride phthalocyanine (ClAlPc) entrapped in cationic and anionic NE to inactivate Candida albicans planktonic cultures and biofilm compared with free ClAlPc. Fungal suspensions were treated with different delivery systems containing ClAlPc and light emitting diode. For planktonic suspensions, colonies were counted and cell metabolism was evaluated by XTT assay. Flow cytometry evaluated cell membrane damage. For biofilms, the metabolic activity was evaluated by XTT and ClAlPc distribution through biofilms was analyzed by confocal laser scanning microscopy (CLSM). Fungal viability was dependent on the delivery system, superficial charge and light dose. Free ClAlPc caused photokilling of the yeast when combined with 100 J cm(-2). Cationic NE-ClAlPc reduced significantly both colony counts and cell metabolism (P < 0.05). In addition, cationic NE-ClAlPc and free ClAlPc caused significant damage to the cell membrane (P < 0.05). For the biofilms, cationic NE-ClAlPc reduced cell metabolism by 70%. Anionic NE-ClAlPc did not present antifungal activity. CLSM showed different accumulation on biofilms between the delivery systems. Although NE system showed a lower activity for planktonic culture, cationic NE-ClAlPc showed better results for Candida biofilms. PMID- 22774874 TI - Editorial comment to higher glycosylated hemoglobin levels increase the risk of overactive bladder syndrome in patients with type 2 diabetes mellitus. PMID- 22774875 TI - The Turkish version of the family impact of assistive technology scale: a validity and reliability study. AB - OBJECTIVE: The purpose of the current study is to estimate the preliminary measurement properties of the Turkish version of Family Impact of assistive technology scale (FIATS-tr). METHOD: The validity and reliability of the scale was performed in two phases. Phase I focused on construction of the Turkish version of the instrument and pilot testing. The scale was translated using the back-translation technique. The comprehensiveness and clarity of the scale was assessed with 20 participants. Phase II included psychometric assessment of the scale using a classical test theory approach. The final version of the scale was pretested with Turkish-speaking parents (46 mothers, four fathers and five caregivers) of 55 chronically disabled children. RESULTS: Test-retest reliability was found to be ICC = 0.931 (95% CI 0.881-0.960) for FIATS-tr total. Cronbach's alpha for the overall FIATS-tr was 0.858. Individual alpha values for FIATS-tr subscales ranged from 0.199 to 0.838. The FIATS-tr total was moderately correlated with the functional independence measure for children (WeeFIM) total (r = 0.688, p < 0.001). CONCLUSIONS: This study showed that overall FIATS-tr appears to have acceptable levels of validity and reliability when used to measure the functional impact of assistive devices. Further study of the constructs and homogeneity of its total and subscales may further improve the internal consistency, validity, and other measurement properties of the FIATS-tr. PMID- 22774876 TI - Direct and indirect effects of perceived social support on health-related quality of life in persons living with HIV/AIDS. AB - Research has established a link between perceived social support and health related quality of life (HRQOL) among persons living with HIV/AIDS. However, little is known about the ways through which social support influences HRQOL. This study examined the direct and indirect effects of perceived social support on physical and mental HRQOL in a sample of 602 adults living with HIV in Ontario, Canada. Participants completed the Medical Outcomes Study-HIV (MOS-HIV) health survey, the MOS-HIV Social Support Scale (MOS-HIV-SSS), and the Center for Epidemiological Studies Depression-Revised scale. Data on demographic and clinical characteristics were also collected. The direct and indirect effects of social support on the two MOS-HIV HRQOL summary measures, that is, physical health summary (PHS) and mental health summary (MHS), were estimated in multiple linear regression analyses. Perceived social support had significant direct effects on PHS (B=0.04, p<0.01) and MHS (B=0.05, p<0.01). It also had significant indirect effect on both PHS (B=0.04, p<0.01) and MHS (B=0.11, p<0.01), mediated by depressive symptoms. Interventions that enhance social support have the potential to contribute to better HRQOL either directly or indirectly by decreasing the deleterious effect of depressive symptoms on HRQOL. PMID- 22774877 TI - Sleep and health: beyond sleep duration and sleepiness? PMID- 22774918 TI - Serum soluble urokinase plasminogen activator receptor (suPAR) in early pregnancy prior to clinical onset of preeclampsia. AB - OBJECTIVE: To examine whether soluble urokinase plasminogen activator receptor (suPAR) in early pregnancy could be a risk marker for later development of preeclampsia. DESIGN: Case-control study. SETTING: Hospital-based. POPULATION: The study comprised 43 pregnant women developing preeclampsia (cases) and 86 pregnant women not developing the disorder (controls). Each case was matched with two controls with respect to pre-pregnancy body mass index, gestational age at time of blood collection, storage time of blood samples and maternal age. METHODS: The samples had been taken predominantly in the first trimester as part of a routine serological screening for rubella, HIV and toxoplasmosis of Norwegian pregnant women, and were analyzed by a commercially available enzyme linked immunosorbent suPARnostic(r) assay kit (ELISA, Virogates, Copenhagen, Denmark). RESULTS: There was no significant difference between median suPAR levels in women who subsequently developed preeclampsia and those who did not (4.5 in the case group vs. 4.3 ng/mL in the control group, p= 0.49). The suPAR levels were relatively high compared with levels in non-pregnant women, reflecting some general physiological responsiveness associated with pregnancy irrespective of preeclampsia. The suPAR level was not related to maternal body mass index, maternal age or sample storage time, nor did it show any association with the following fetal characteristics: body weight, body length, placental weight, delivery method or gender. CONCLUSION: suPAR did not appear to be a useful early pre-clinical marker of preeclampsia. PMID- 22774919 TI - Mesenteric arteries responsiveness to acute variations of wall shear stress is impaired in rats with liver cirrhosis. AB - OBJECTIVE: In liver cirrhosis, excessive splanchnic vasodilation is due to abnormal synthesis of endogenous vasodilators and to decreased sensitivity to vasoconstrictors. The role of mechanical stimuli such as wall shear stress (WSS) on splanchnic circulation remains unclear. The aim of this study was to assess the vasodilation induced by wall shear stress (WSS) and acute changes in blood flow in the mesenteric arteries in an experimental model of liver cirrhosis. MATERIALS AND METHODS: The effect of acute changes in intraluminal flow (0, 10, and 20 MUl/min) and WSS on the diameter of the mesenteric arteries (diameters <500 MUm) of control and cirrhotic rats was assessed, at baseline and after the inhibition of nitric oxide synthase, cyclooxygenase and hemeoxygenase. Concentration-response curves to phenylephrine were also obtained. RESULTS: In controls, the increase in intraluminal flow led to a significant increase in arterial diameter (p < 0.05), while WSS remained stable; the effect was maintained in vessels pre-constricted with phenylephrine, blocked by the exposure to indomethacin and L-NAME and restored by the subsequent addition of chromium mesoporphyrin (p < 0.05). In cirrhotic arteries, arterial diameters did not change in response to acute increase in flow, neither at baseline nor after exposure to indomethacin and L-NAME, while WSS increased (p < 0.01). Responsiveness to flow was partially restored (p < 0.05) after exposure of the arteries to chromium mesoporphyrin in addition to indomethacin and L-NAME. CONCLUSIONS: Arteries from cirrhotic rats showed an abolished responsiveness to acute variations in flow, which exposes the mesenteric endothelium to sudden variations in WSS. PMID- 22774920 TI - Considerations for the optimal use of immunoglobulin. AB - Immunoglobulins are large Y-shaped proteins produced by B-cells and plasma cells that are used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. Immunoglobulin G (IgG) preparations are approved by the US Food and Drug Administration for the treatment of primary immunodeficiency disease, idiopathic thrombocytopenic purpura, Kawasaki disease, chronic lymphocytic leukemia with frequent infections, bone marrow transplantation, to prevent infection in pediatric human immunodeficiency virus, and chronic inflammatory demyelinating polyneuropathy. However, IgG products are frequently used off label in many autoimmune conditions. The advent of numerous intravenous and subcutaneous formulations of IgG presents new opportunities impacting patient preferences, site of care, and costs. The appropriate and optimal use of IgG is reviewed based on discussions from an expert roundtable panel and review of the scientific literature. Clinicians and payers should consider patient preferences, evidence- based guidelines, and policies when selecting an IgG product. PMID- 22774921 TI - Finger tapping-related activation differences in treatment-naive pediatric Tourette syndrome: a comparison of the preferred and nonpreferred hand. AB - BACKGROUND: Disturbances of motor circuitry are commonly encountered in Tourette syndrome (TS). The aim of this study was to investigate simple motor performance differences between boys with TS and healthy controls. METHODS: We attempted to provide insight into motor network alterations by studying a group of treatment naive patients suffering from 'pure' TS, i.e., without comorbid symptomatology at an early stage of disease. We used functional MRI to compare activation patterns during right (preferred) and left (nonpreferred) index finger tapping between 22 TS boys (12.6 +/- 1.7 years) and 22 age-matched healthy control boys. RESULTS: Boys with TS revealed altered motor network recruitment for right (dominant) and left (nondominant) index finger tapping. Brain activation patterns in response to index finger tapping of the nonpreferred left hand reflected the most prominent differences, including activation decrease in contralateral sensorimotor cortex while recruiting premotor and prefrontal regions along with the left inferior parietal lobule to a greater extent. CONCLUSIONS: This study demonstrates clear functional differences of simple index finger tapping in early-stage TS. We suggest that this reflects the requirement for additional brain networks to keep a normal performance level during the actual task and adaptive mechanisms due to continuous tic suppression and performance in TS. PMID- 22774923 TI - Inhibition of Sporosarcina pasteurii under anoxic conditions: implications for subsurface carbonate precipitation and remediation via ureolysis. AB - The use of Sporosarcina pasteurii to precipitate calcium carbonate in the anoxic subsurface via ureolysis has been proposed for reducing porosity and sealing fractures in rocks. Here we show that S. pasteurii is unable to grow anaerobically and that the ureolytic activity previously shown under anoxic conditions is a consequence of the urease enzyme already present in the cells of the aerobically grown inoculum. The implications are discussed, suggesting that de novo synthesis of urease under anoxic conditions is not possible and that ureolysis may decline over time without repeated injection of S. pasteurii as the urease enzyme degrades and/or becomes inhibited. Augmentation with a different ureolytic species that is able to grow anaerobically or stimulation of natural communities may be preferable for carbonate precipitation over the long term. PMID- 22774922 TI - Exendin-4 reverts behavioural and neurochemical dysfunction in a pre-motor rodent model of Parkinson's disease with noradrenergic deficit. AB - BACKGROUND AND PURPOSE Parkinson's disease (PD) is characterized by progressive dopaminergic cell loss; however, the noradrenergic system exhibits degeneration as well. Noradrenergic deficit in PD may be responsible for certain non-motor symptoms of the pathology, including psychiatric disorders and cognitive decline. The aim of this study was to generate a pre-motor rodent model of PD with noradrenergic denervation, and to assess whether treatment with exendin-4 (EX-4), a glucagon-like peptide 1 receptor agonist, could reverse impairment exhibited by our model. EXPERIMENTAL APPROACH We generated a model of PD utilizing N-(2 chloroethyl)-N-ethyl-2-bromobenzylamine and 6-hydroxydopamine to create partial lesions of both the noradrenergic and dopaminergic systems respectively. We then assessed the validity of our model using an array of behavioural paradigms and biochemical techniques. Finally, we administered EX-4 over a 1 week period to determine therapeutic efficacy. KEY RESULTS Our model exhibits anhedonia and decreased object recognition as indicated by a decrease in sucrose preference, increased immobility in the forced swim test and reduced novel object exploration. Tissue and extracellular dopamine and noradrenaline were reduced in the frontal cortex and striatum. TH+ cell counts decreased in the locus coeruleus and substantia nigra. Treatment with EX-4 reversed behavioural impairment and restored extracellular/tissue levels of both dopamine and noradrenaline and TH+ cell counts. CONCLUSION AND IMPLICATIONS We conclude that early treatment with EX 4 may reverse certain neuropsychiatric dysfunction and restore dopamine and noradrenaline content. PMID- 22774925 TI - Catch the wave! Time-window sequential analysis of alertness stimulation in individuals with profound intellectual and multiple disabilities. AB - BACKGROUND: While optimally activities are provided at those moments when the individual with profound intellectual and multiple disabilities (PIMD) is 'focused on the environment' or 'alert', detailed information about the impact that the design and timing of the activity has on alertness is lacking. Therefore, the aim of the present study is to shed light on the sequential relationship between different stimuli and alertness levels in individuals with PIMD. METHOD: Video observations were conducted for 24 participants during one-on one interactions with a direct support person in multisensory environments. Time window sequential analyses were conducted for the 120 s following four different stimuli. RESULTS: For the different stimuli, different patterns in terms of alertness became apparent. Following visual stimuli, the alertness levels of the individuals with PIMD changed in waves of about 20 s from 'active alert' to 'passive alert'. While auditory and tactile stimuli led to 'alert' reactions shortly after the stimulation, alertness levels decreased between seconds 20 and 120. Reactions to vestibular stimuli were only visible after 60 s; these were 'active alert' or 'withdrawn'. CONCLUSIONS: The results of the present study show that individuals with PIMD show their reactions to stimuli only slightly, so that 'waves' might reflect the optimal alertness pattern for learning and development. Consequently, it is especially important that direct support persons follow and stimulate these individual 'waves' in the activities they provide to their clients. PMID- 22774926 TI - Sarcosaprophagous Diptera assemblages in natural habitats in central Spain: spatial and seasonal changes in composition. AB - The composition and spatial distribution of sarcosaprophagous Diptera assemblages were studied using carrion-baited traps along a bioclimatic gradient of natural habitats in central Spain throughout the different seasons during 1 year. Calliphoridae and Muscidae were the most abundant families, accounting for, respectively, 41.9% and 35.1% of all Diptera specimens collected. Other abundant families were Heleomyzidae (8.4%), Sarcophagidae (6.9%) and Piophilidae (5.1%). Fly assemblage compositions differed among bioclimatic levels, with Chrysomya albiceps (Wiedemann) (Diptera: Calliphoridae) being the dominant species in mesomediterranean habitats, Muscina levida (Harris) (Diptera: Muscidae) the dominant species in supramediterranean habitats, and Prochyliza nigrimana (Meigen) (Diptera: Piophilidae) the dominant species in oromediterranean habitats. Differences in assemblage composition were also found among seasons. Thermophobic species such as Calliphora vicina Robineau-Desvoidy (Diptera: Calliphoridae) and some species of Heleomyzidae were well represented during autumn, winter and spring in the three bioclimatic levels sampled. By contrast, thermophilic species such as Ch. albiceps and Lucilia sericata (Meigen) (Diptera: Calliphoridae) and most Muscidae and Sarcophagidae species were more abundant during summer and in mesomediterranean habitats located at lower elevations. Knowledge of the preferences of some species for certain habitats may be of ecological and forensic value and may establish a starting point for further research. PMID- 22774927 TI - Computer-assisted analysis of spontaneous speech: quantification of basic parameters in aphasic and unimpaired language. AB - Although generally accepted as an important part of aphasia assessment, detailed analysis of spontaneous speech is rarely carried out in clinical practice mostly due to time limitations. The Aachener Sprachanalyse (ASPA; Aachen Speech Analysis) is a computer-assisted method for the quantitative analysis of German spontaneous speech that allows for a detailed assessment by means of linguistic basic parameters in an acceptable amount of time. It has previously been proven sensitive for monitoring changes over time. In this study, we present data of 52 aphasic participants whose spontaneous speech was analyzed retrospectively before and after an intensive therapy program. The measured changes are evaluated with reference to normative data of 60 non-brain-damaged speakers. Results confirm good sensitivity to document changes over time. Clinical relevance of changes is assessed with reference to critical score ranges derived from the normative data. Findings provide further evidence of the clinical applicability and usefulness of ASPA. PMID- 22774928 TI - Intensive treatment of dysarthria secondary to stroke. AB - This study investigated the impact of a well-defined behavioral dysarthria treatment on acoustic and perceptual measures of speech in four adults with dysarthria secondary to stroke. A single-subject A-B-A experimental design was used to measure the effects of the Lee Silverman Voice Treatment (LSVT((r)) LOUD) on the speech of individual participants. Dependent measures included vocal sound pressure level, phonatory stability, vowel space area, and listener ratings of speech, voice and intelligibility. Statistically significant improvements (p < 0.05) in vocal dB SPL and phonatory stability as well as larger vowel space area were present for all participants. Listener ratings suggested improved voice quality and more natural speech post-treatment. Speech intelligibility scores improved for one of four participants. These data suggest that people with dysarthria secondary to stroke can respond positively to intensive speech treatments such as LSVT. Further studies are needed to investigate speech treatments specific to stroke. PMID- 22774930 TI - Between-word processes in children with speech difficulties: insights from a usage-based approach to phonology. AB - There are some children with speech and/or language difficulties who are significantly more difficult to understand in connected speech than in single words. The study reported here explores the between-word behaviours of three such children, aged 11;8, 12;2 and 12;10. It focuses on whether these patterns could be accounted for by lenition, as suggested by a usage-based approach to phonology. The children carried out a repetition task, with sentences containing environments that can trigger assimilation and elision. Speech elicited was examined using a combination of perceptual and electropalatographic (EPG) analysis. All of the children produced instances of word boundary behaviours reported in adult speech, as well as some which are considered to be atypical. It is argued that all of these phenomena can be viewed as lenition, and that a usage based approach to phonology has potential for providing a valuable framework for the description of between-word processes in disordered speech. PMID- 22774929 TI - Dramatic effects of speech task on motor and linguistic planning in severely dysfluent parkinsonian speech. AB - In motor speech disorders, dysarthric features impacting intelligibility, articulation, fluency and voice emerge more saliently in conversation than in repetition, reading or singing. A role of the basal ganglia in these task discrepancies has been identified. Further, more recent studies of naturalistic speech in basal ganglia dysfunction have revealed that formulaic language is more impaired than novel language. This descriptive study extends these observations to a case of severely dysfluent dysarthria due to a parkinsonian syndrome. Dysfluencies were quantified and compared for conversation, two forms of repetition, reading, recited speech and singing. Other measures examined phonetic inventories, word forms and formulaic language. Phonetic, syllabic and lexical dysfluencies were more abundant in conversation than in other task conditions. Formulaic expressions in conversation were reduced compared to normal speakers. A proposed explanation supports the notion that the basal ganglia contribute to formulation of internal models for execution of speech. PMID- 22774931 TI - Development of 14 English grammatical morphemes in Spanish-English preschoolers. AB - Previous research in the USA studying Spanish-English bilingual children's language development has largely focused on children's developing abilities in Spanish. However, relatively little research has been conducted on children's English grammatical development. Therefore, the purpose of this study was to examine the English grammatical development of bilingual (Spanish-English) Head Start children during the preschool years. The goals were to determine (a) whether there are differences in children's productions of English grammatical morphemes based on timing of English exposure and (b) which morphological structures met mastery, emerging and early emerging levels of production by bilingual children. These aims were accomplished through in-depth analyses of spontaneous language samples collected over a two-year period in Head Start. Comparisons were made between Spanish-speaking children who were exposed to English at home from birth (home English communication (HEC)) and Spanish speaking children who were not expected to communicate in English until their entry into Head Start (school English communication (SEC)). Results indicated that children in the HEC group mastered more morphemes earlier than the children in the SEC group; however, by the end of children's second year in Head Start both groups had mastered a similar number of morphemes. Additionally, the children in both groups differed in which morphemes were mastered at the end of Head Start when compared to monolingual English-speaking children. The results of this investigation provide information to clinicians about typical English grammatical development of Spanish-English preschool children. PMID- 22774932 TI - Functional expression of the multi-subunit type calcium/proton antiporter from Thermomicrobium roseum. AB - Multiple resistance and pH adaptation (Mrp) antiporters are widely distributed in various prokaryotes and have been reported to function as a hetero-oligomeric monovalent cation/proton antiporter, which exchanges a cytoplasmic monovalent cation (Na(+), Li(+), and/or K(+)) with extracellular H(+). In many organisms, they are essential for survival in alkaline or saline environments. Here, we report that the Mrp antiporter from the thermophilic gram-negative bacterium, Thermomicrobium roseum, does not catalyze monovalent cation/proton antiport like the Mrp antiporters studied to date, but catalyzes Ca(2+)/H(+) antiport in Escherichia coli membrane vesicles. PMID- 22774933 TI - Hydrogen peroxide and nitric oxide mediated cold- and dehydration-induced myo inositol phosphate synthase that confers multiple resistances to abiotic stresses. AB - myo-Inositol phosphate synthase (MIPS) is the key enzyme of myo-inositol synthesis, which is a central molecule required for cell metabolism and plant growth as a precursor to a large variety of compounds. A full-length fragment of MfMIPS1 cDNA was cloned from Medicago falcata that is more cold-tolerant than Medicago sativa. While MfMIPS1 transcript was induced in response to cold, dehydration and salt stress, MIPS transcript and myo-inositol were maintained longer and at a higher level in M. falcata than in M. sativa during cold acclimation at 5 degrees C. MfMIPS1 transcript was induced by hydrogen peroxide (H(2) O(2)) and nitric oxide (NO), but was not responsive to abscisic acid (ABA). Pharmacological experiments revealed that H(2) O(2) and NO are involved in the regulation of MfMIPS1 expression by cold and dehydration, but not by salt. Overexpression of MfMIPS1 in tobacco increased the MIPS activity and levels of myo-inositol, galactinol and raffinose, resulting in enhanced resistance to chilling, drought and salt stresses in transgenic tobacco plants. It is suggested that MfMIPS1 is induced by diverse environmental factors and confers resistance to various abiotic stresses. PMID- 22774934 TI - Hydrogen-bonded double-proton transfer in five guanine-cytosine base pairs after hydrogen atom addition. AB - The double-proton transfer reactions in Watson-Crick guanine-cytosine (GC) base pairs after hydrogen atom addition are studied theoretically. The structural changes and energy differences among the structures are compared to explore the double-proton transfer mechanisms, concerted and stepwise. The concerted mechanism is found in all five radicals (GC+H)(*) considered, while the stepwise mechanism is predicted only for structures G-H(*)C(C6) and H(*)G(N7)-C. The geometrical features have been found to change regularly in the concerted double proton transfer. This is different from the single-proton transfer, for which the structural perturbations are dispersed throughout the GC base pair. The energy analyses demonstrate that the concerted double-proton transfer mechanism is more favorable in the gas phase, while the stepwise mechanism dominates in water. The structures of proton transfer products become less favored energetically. PMID- 22774935 TI - Mitochondrial dysfunction is involved in P2X7 receptor-mediated neuronal cell death. AB - P2X7 receptor (P2X7R) is known to be a 'death receptor' in immune cells, but its functional expression in non-immune cells such as neurons is controversial. Here, we examined the involvement of P2X7R activation and mitochondrial dysfunction in ATP-induced neuronal death in cultured cortical neurons. In P2X7R- and pannexin-1 expressing neuron cultures, 5 or more mM ATP or 0.1 or more mM BzATP induced neuronal death including apoptosis, and cell death was prevented by oxATP, P2X7R selective antagonists. ATP-treated neurons exhibited Ca(2+) entry and YO-PRO-1 uptake, the former being inhibited by oxATP and A438079, and the latter by oxATP and carbenoxolone, while P2X7R antagonism with oxATP, but not pannexin-1 blocking with carbenoxolone, prevented the ATP-induced neuronal death. The ATP treatment induced reactive oxygen species generation through activation of NADPH oxidase and activated poly(ADP-ribose) polymerase, but both of them made no or negligible contribution to the neuronal death. Rhodamine123 efflux from neuronal mitochondria was increased by the ATP-treatment and was inhibited by oxATP, and a mitochondrial permeability transition pore inhibitor, cyclosporine A, significantly decreased the ATP-induced neuronal death. In ATP-treated neurons, the cleavage of pro-caspase-3 was increased, and caspase inhibitors, Q-VD-OPh and Z-DEVD-FMK, inhibited the neuronal death. The cleavage of apoptosis-inducing factor was increased, and calpain inhibitors, MDL28170 and PD151746, inhibited the neuronal death. These findings suggested that P2X7R was functionally expressed by cortical neuron cultures, and its activation-triggered Ca(2+) entry and mitochondrial dysfunction played important roles in the ATP-induced neuronal death. PMID- 22774936 TI - Staff's perception of adolescent aggressive behaviour in four European forensic units: a qualitative interview study. AB - BACKGROUND: Aggressive behaviour among patients is extremely common in forensic adolescent psychiatry compromising the safety of the treatment milieu and posing a treatment challenge to the staff. The staff's perception of aggression is likely to contribute to the aggression management practices among disturbed adolescents. AIMS: To examine staff's perceptions of adolescent aggressive behaviour and factors contributing it. METHODS: Qualitative interviews were conducted in four adolescent forensic units in four European countries. Data was analysed using qualitative content analysis. FINDINGS: Aggressive behaviour was perceived to be verbal and physical in nature with various levels of severity. Several factors were perceived to contribute to aggressive acts, including adolescents' early life experiences. Participants mainly shared perceptions of adolescent aggressive behaviour in the four units studied. CONCLUSIONS: The study provides new international knowledge about how staff perceive adolescent aggressive behaviour in the forensic setting. The shared understanding of adolescents' aggressive behaviour enables the implementation of safe, ethically sound and more consistent aggression management in clinical forensic practice. Reduced occurrence of aggression may improve the therapeutic milieu of the unit and may strengthen the staff's occupational health. PMID- 22774937 TI - Stabilization of ferromagnetic order in La(0.7)Sr(0.3)MnO3-SrRuO3 Superlattices. AB - The study of spatially confined complex oxides is of wide interest, since correlated electrons at interfaces might form exotic phases. Here La(0.7)Sr(0.3)MnO(3)/SrRuO(3) superlattices with coherently grown interfaces were studied by structural techniques, magnetization, and magnetotransport measurements. Magnetization measurements showed that ferromagnetic order in ultrathin La(0.7)Sr(0.3)MnO(3) layers is stabilized in the superlattices down to layer thicknesses of at least two unit cells. This stabilization is destroyed, if the ferromagnetic layers are separated by two unit cell thick SrTiO(3) layers. The resistivity of the superlattices showed metallic behavior and was dominated by the conducting SrRuO(3) layers, the off-diagonal resistivity showed an anomalous Hall effect from both SrRuO(3) and La(0.7)Sr(0.3)MnO(3) layers. This shows that the La(0.7)Sr(0.3)MnO(3) layers are not only ferromagnetic but also highly conducting; probably a conducting hole gas is induced at the interfaces that stabilizes the ferromagnetic order. This result opens up an alternative route for the fabrication of two-dimensional systems with long-range ferromagnetic order. PMID- 22774938 TI - Panoramic radiographic evaluation of the mandibular morphological changes in elderly dentate and edentulous subjects. AB - OBJECTIVE: The aim of the present study was to analyze the changes in the gonial angle, ramus height, condyle height and cortical bone thickness in relation to gender and dental status in elderly patients. MATERIALS AND METHODS: The study population comprised 240 patients (age ranged from 60-69 years) who had digital panoramic radiographs taken for various purposes. One group consisted of 120 patients, 60 men and 60 women, who had all natural teeth present except for third molars. The second group consisted of the remaining 120 patients (60 men and 60 women) who were in a completely edentulous state (maxilla and mandible). The gonial angle, ramus height, condylar height and cortical bone thickness of the mandible were measured by computer software on their panoramic radiographs. RESULTS: Women showed larger gonial angles than men, while men had greater cortical bone thickness and ramus height (p < 0.05). However, no significant difference in condylar height was found between both genders (p > 0.05). Edentulous subjects had a larger gonial angle than dentate subjects, while dentate subjects had greater cortical bone thickness on both sides and left side of condylar height (p < 0.05). The gonial angle had statistically negative correlations with cortical bone thickness and ramus height, regardless of gender. CONCLUSIONS: The outcomes of the present study indicate that the edentulous women undergo morphological changes of the mandible influenced by the dental status more than men. PMID- 22774939 TI - Photophysical properties of sol-gel derived luminescent silicone hybrids synthesized via facile amino-ene reaction. AB - Novel luminescent silicone hybrids (LSHs) containing lanthanide ions were prepared via different sol-gel processes. The precursor, dimethyl ester functionalized silane, was synthesized via a facile amino-ene reaction. The coordinated assembly of the ester ligands and lanthanide ions (Eu(3+), Tb(3+) and Dy(3+)) occurred. The ester ligands were immobilized onto the Si-O network backbone during the preparation of the silicone hybrid materials. The particle size can be controlled to ca 50 nm by adjusting the solvent ratio. The obtained materials were characterized by Fourier transform infrared, (1)H nuclear magnetic resonance spectroscopy (NMR), (13)C NMR, (28)Si NMR, X-ray diffraction, X-ray photoelectron spectroscopy, thermogravimetric analysis, high-resolution scanning electronic microscopy and luminescent (excitation and emission) spectroscopy. The coordination state and photophysical performance of the compounds were studied in detail. The terbium- and europium-containing materials show sharp green and red emissions, respectively, which indicate that efficient intramolecular energy transfer took place in these LSHs. PMID- 22774940 TI - General practitioners' views on perceived and actual gains, benefits and barriers associated with the implementation of an Australian health assessment for people with intellectual disability. AB - BACKGROUND: Health assessments for people with intellectual disability have been implemented in the UK, New Zealand and Australia, and have led to improved health outcomes. The Comprehensive Health Assessment Program (CHAP) has been shown to improve the health of people with intellectual disability. Similar to other health assessments, it is designed to address healthcare needs, many of which are often overlooked in this population, through better communication between the general practitioner (GP), support worker and the person with intellectual disability. This study investigates GP views of the perceived and actual benefits, gains and barriers associated with its uptake and use in practice. METHOD: As part of a larger randomised controlled trial of the CHAP, 46 GPs in Queensland, Australia, completed two telephone interviews that included open ended questions about their perceptions of the health assessment. The GPs were enrolled in the intervention arm of the trial. Interviews took place at commencement and conclusion of the trial to gain the views of GPs as they experienced using the CHAP. Thematic analysis was used to identify key themes and patterns from the GP responses. RESULTS: Four themes were identified: better healthcare and uncertain benefits captured GP perceptions of the potential gains associated with use of the CHAP, while two further themes, organisational barriers in the general practice setting and engagement across the healthcare triad highlighted strengths and barriers related to implementation. Anticipated concerns about time raised by GPs at commencement of the trial were borne out in practice, but concerns about communication and cooperation of people with disabilities were not. Matters associated with support worker engagement emerged as an area of concern. CONCLUSIONS: GPs perceive the CHAP as a structured and comprehensive approach to the detection of medical problems as well as an aid in overcoming communication barriers between the doctor and the person with disability. Our findings suggest that some GPs may find it difficult to predict the benefits of using health assessments such as the CHAP. Achieving optimal uptake is likely to require attention at policy and systems levels to address: GP time constraints in providing healthcare to this population; enhancement of support worker training and organisational structures to encourage comprehensive health assessment and follow-up activities; and GP awareness of the improved health outcomes shown to derive from the use of comprehensive health assessments. PMID- 22774941 TI - Discriminating primary clinical states in bipolar disorder with a comprehensive symptom scale. AB - OBJECTIVE: We assessed the spectrum and severity of bipolar symptoms that differentiated bipolar disorder (BD) clinical states, employing the Bipolar Inventory of Symptoms Scale (BISS) which provides a broader item range of traditional depression and mania rating scales. We addressed symptoms differentiating mixed states from depression or mania/hypomania. METHOD: One hundred and sixteen subjects who met DSM-IV-TR criteria for BD and were currently in a depressed, manic/hypomanic, mixed episode, or recovered state were interviewed using the BISS. RESULTS: A subset of manic items differed between mixed episodes and mania/hypomania or depression. Most anxiety items were more severe in mixed subjects. BISS Depression and Manic subscales differentiated episodes from recovered status. The majority of depression and manic symptoms differentiated mood states in the predicted direction. Mixed episodes had overall greater mood severity than manic/hypomanic episodes or depressed episodes. CONCLUSION: These results indicate that a small subset of symptoms, several of which are absent in DSM-IV-TR criteria and traditional rating scales for bipolar studies, aid in distinguishing mixed episodes from depressive or manic/hypomanic episodes. The results also support the utility of a comprehensive BD symptom scale in distinguishing primary clinical states of BD. PMID- 22774942 TI - The habenula couples the dopaminergic and the serotonergic systems: application to depression in Parkinson's disease. AB - A high percentage of patients with Parkinson's disease suffer from depression in addition to their motor disabilities. However, the etiology of this depression and its relation to Parkinson's disease are unknown. Within the framework of the monoamine deficiency hypothesis of depression, we propose that the dopaminergic and serotonergic systems are coupled by the lateral habenula, and argue that altered basal ganglia activity leads to lateral habenula hyperactivity, which in turn down-regulates the serotonergic system, resulting in depressive symptoms in patients with Parkinson's disease. We tested this hypothesis using the unilateral 6-hydroxydopamine hemiparkinsonian rat model of Parkinson's disease. Behavior was assessed using the novelty suppressed feeding and forced swim tests, and the effective connectivity of the serotonergic system was estimated by manganese enhanced magnetic resonance imaging of the raphe nuclei. The results show depression-like behaviors and reduced raphe connectivity with the lateral habenula, dentate gyrus of the hippocampus, thalamus and hypothalamus in the 6 hydroxydopamine rat groups. More importantly, partial restoration of the raphe connectivity and partial normalization of behavior were achieved by dopamine replacement therapy (apomorphine, 10 mg/kg, s.c. daily). Furthermore, nearly complete behavioral normalization was reached after a bilateral electric lesion of the lateral habenula. These findings provide a plausible link between Parkinson's disease and depression and open up avenues for new therapeutic interventions in depression and possibly in Parkinson's disease. PMID- 22774978 TI - Enhanced photocatalytic activity of ZnO microspheres via hybridization with CuInSe2 and CuInS2 nanocrystals. AB - ZnO microspheres sensitized by CuInSe(2) and CuInS(2) nanoparticles, which were synthesized by a solvothermal method and have a size about 20 and 3.5 nm, respectively, were used to a photodegradation of rhodamine B under an irradiation of mercury lamp. Results show that the photocatalytic activities of the ZnO/CuInSe(2) and the ZnO/CuInS(2) are much higher than that of the ZnO microspheres because of a formation of the heterojunction in two systems. It is also noted that the ZnO/CuInS(2) exhibits a higher photocatalytic activity than the ZnO/CuInSe(2), which is probably related to more suitable band gap to sunlight for CuInS(2) nanocrystals and the larger specific surface due to a small size. Particularly, the ZnO/CuInSe(2)/CuInS(2) shows the highest photocatalytic activities in all measured photocatalysts, which should be attributed to the formation of double heterojunctions among ZnO, CuInSe(2), and CuInS(2). PMID- 22774979 TI - An index for staging facial lipoatrophy and evaluation of the efficacy of the treatment with polymethylmethacrylate in HIV/AIDS patients: a pilot study. AB - BACKGROUND: Treatment of facial lipoatrophy of HIV/AIDS patients is mandatory by law in Brazil due to its negative impact on their quality of life. The index for facial lipoatrophy (ILA) is used as one of the inclusion criteria for patient treatment. OBJECTIVES: To define a correct diagnosis and staging of facial lipoatrophy, by employing the ILA. PATIENTS AND METHODS: This is an observational study of a series of case reports from patients submitted to facial lipoatrophy evaluation through ILA and treated with polymethylmethacrylate (PMMA) fillers. Facial lipoatrophy was classified in grades from I to IV, corresponding to mild, moderate, severe and very severe stage, according to ILA. Response to the treatment was defined as excellent (>= 91%), good (71-90%), moderate (51-70%) and insufficient (<= 50%). RESULTS: A total of 20 patients were included in this study: 18 men and two women. Median age was 49 years (35-61) and average ILA was 9.9 (7.2-16.8). Ten patients presented facial lipoatrophy grade II (moderate), 5 grade III (severe) and 5 grade IV (very severe). The average volume of PMMA used was 13 mL (5.5-22 mL). All patients showed good or excellent response, with a median of 86% (74-100%). The most typical adverse effect was local oedema but there were no late adverse effects. CONCLUSION: The ILA is an excellent method for evaluation of facial lipoatrophy and also for the assessment of the response to therapy. Facial filling with PMMA showed efficacy and safety in the treatment of facial lipoatrophy in HIV/AIDS patients. PMID- 22774980 TI - Early origins of heart disease: low birth weight and the role of the insulin-like growth factor system in cardiac hypertrophy. AB - Epidemiological studies indicate that poor growth before birth is associated with left ventricular hypertrophy and an increased risk of death from heart disease later in life. In fetal life, the insulin-like growth factor (IGF) system has been implicated in physiological growth of the heart, whereas in postnatal life IGFs can be involved in both physiological and pathological cardiac hypertrophy. A reduction in substrate supply in fetal life, resulting in chronic hypoxaemia and intrauterine growth restriction, results in increased cardiac IGF-1R, IGF-2 and IGF-2R gene expression; and there is also evidence for a role of the IGF-2 receptor in the ensuing cardiac hypertrophy. The persistent high level of cardiac IGF-2R gene expression from fetal to postnatal life may be due to epigenetic changes in key cardiac hypertrophy regulatory pathways. PMID- 22774981 TI - K/B*N serum transfer arthritis is delayed and less severe in leukaemia inhibitory factor (LIF)-deficient mice. AB - This study is investigating the role of leukaemia inhibitory factor (LIF) in the development of inflammation and joint damage in the mouse K/B*N serum transfer arthritis model. LIF knock-out (LIF(-/-)) mice were generated by mating heterozygote females (LIF(+/-)) with heterozygote males. Arthritis was induced in 8-20-week-old LIF knock-out mice (LIF(-/-)) by intraperitoneal injection of pooled K/B*N sera (50 ul) on days 0 and 2. Clinical disease was scored daily for 6 days. Safranin-O and haematoxylin-stained sections were scored for synovitis, joint space exudate, cartilage degradation and bone damage. RNA was extracted from ankle joints and used to investigate gene expression levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1, LIF, LIF receptor, oncostatin M (OSM), OSM receptor, IL-6 and their common receptor subunit gp130 by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results show that wild-type mice developed severe clinically overt polyarthritis. In contrast, LIF( /-) mice showed a more than 50% reduction in clinical arthritis severity. Significantly lower histological scores were observed in LIF(-/-) mice compared to wild-type disease controls. LIF(-/-) mice had histopathological scores that were similar to normal healthy mice. IL-6 subfamily cytokine and receptor subunit expression remained unchanged. The expression levels for IL-6 were reduced significantly in all the diseased mice, whether wild-type or LIF(-/-) mice (P < 0.001), compared to healthy wild-type mice. We conclude that LIF contributes to the development of disease in the K/B*N serum transfer model of arthritis. These results provide further evidence for the role of LIF in inflammation and cartilage bone resorption and provide impetus to test the effects of LIF blockade as a therapeutic strategy in rheumatoid arthritis. PMID- 22774982 TI - Susceptibility to autoimmune myocarditis is associated with intrinsic differences in CD4(+) T cells. AB - A.SW and B10.S mice share the same major histocompatibility complex (MHC) haplotype (H-2(s)). However, A.SW mice are susceptible to experimental autoimmune myocarditis (EAM) and develop severe disease after immunization with myosin, whereas B10.S mice are resistant. We found that naive A.SW mice have intrinsically increased total CD4(+) T cell counts and increased proportions of CD4(+) T cells in their spleens compared to B10.S mice. Among total CD4(+) T cells, naive A.SW mice have a lower relative frequency of forkhead box protein 3 (FoxP3(+))CD25(+) regulatory T cells (T(regs)). A.SW mice also had a higher proportion of CD4(+) T cells and a lower proportion of T(regs) in their hearts and spleen during EAM, with greater T cell activation and proliferation, compared to B10.S mice. These differences in the T cell compartment were not antigen specific, as ovalbumin/complete Freund's adjuvant (OVA/CFA) or CFA immunization elicited the same differences in CD4(+) T cells and T(regs) between A.SW and B10.S mice. Moreover, A.SW mice had more T helper type 17 (Th17) cells and B10.S had more Th1 cells in their hearts. The higher percentage of CD4(+) T cells and their enhanced potential to differentiate towards the Th17 pathway was also observed in naive A.SW mice. Interleukin (IL)-6 is required for Th17 induction. Interestingly, IL-6Ralpha expression was greater on naive A.SW CD4(+) T cells, compared to B10.S CD4(+) T cells, indicating that this intrinsic difference, together with a relatively lower T(reg) proportion of CD4(+) T cells, might lead to heightened Th17 responses and greater susceptibility to autoimmunity in A.SW mice. PMID- 22774983 TI - Selective localization of T helper subsets in labial salivary glands from primary Sjogren's syndrome patients. AB - The aim of this study was to investigate the initiation and progression of autoimmune damage in the lesions of labial salivary glands (LSGs) from primary Sjogren's syndrome (SS) patients by examining the selective localization of T helper (Th) subsets such as Th1, Th2, Th17 regulatory T cells (T(regs)) and follicular T helper cells (Tfh). The expression of cytokines and transcription factors associated with these Th subsets in the LSGs from 54 SS patients and 16 healthy controls was examined using real-time polymerase chain reaction (PCR) and immunostaining. Additionally, infiltrating lymphocytes without germinal centre (GC(-)) and with GC (GC(+)) in the LSGs specimens from eight SS patients were extracted selectively by laser capture microdissection (LCM). The mRNA expression of these molecules was compared between the two sample groups of GC(-) and GC(+) by real-time PCR. The mRNA expression of cytokines and transcription factors of all T helper (Th) subsets in the LSGs from the SS patients was increased significantly in comparison with controls. In LSGs from the SS patients, Th2 and Tfh was associated closely with strong lymphocytic infiltration; however, Th1, Th17 and T(regs) was not. In the selectively extracted lesions of LSGs, Th1 and Th17-related molecules were detected strongly in the GC(-), while Th2 and Tfh related molecules were detected in the GC(+). In contrast, no significant association with strong lymphocytic infiltration was observed in T(reg)-related molecules. These results indicate that SS has selective localization of Th subsets such as Th1, Th2, Th17 and Tfh in the LSGs, which is associated closely with disease severity and/or status. SS might be initiated by Th1 and Th17 cells, and then progressed by Th2 and Tfh cells via GC formation. PMID- 22774984 TI - Sublytic complement protects prostate cancer cells from tumour necrosis factor alpha-induced cell death. AB - Inflammation is a critical component of tumour progression. Although complement and tumour necrosis factor (TNF)-alpha potentially exert significant anti-tumour effects, both mediators may also promote tumour progression. It has been demonstrated that sublytic complement confers resistance on tumour cells not only against lytic complement, but also other danger molecules such as perforin. In low concentrations, TNF promotes survival of malignant cells rather than exerting cytotoxic activity. In this study, we tested if sublytic complement is able to interfere with TNF-mediated tumour cell killing. Our results demonstrate that either subcytotoxic concentrations of TNF or sublytic complement rescue prostate carcinoma cells (DU145) from TNF-alpha-mediated cell death. Upon pretreatment with low-dose TNF-alpha, but not upon pre-exposure to sublytic complement, TNF resistance was associated with the down-regulation of TNF receptor 1 (TNF-R1) expression. Complement-induced protection against TNF-mediated apoptosis accompanied the induction of anti-apoptotic proteins [B cell leukaemia/lymphoma (Bcl)-2 and Bcl-xL] at an early stage followed by inhibition of the TNF-induced decrease in the amount of Bcl-2 and Bcl-xL. Cell protection also accompanied the inhibition of caspase-8 activation, poly (ADP-ribose) polymerase (PARP)-1 cleavage and the activation of nuclear factor (NF)-kappaB. Our data extend our current view on the induction of tumour cell resistance against cytotoxic mediators supporting the role of the tumour microenvironment in mediating protection against the anti-cancer immune response. PMID- 22774985 TI - Highly conserved CDR3 region in circulating CD4(+)Vbeta5(+) T cells may be associated with cytotoxic activity in Chagas disease. AB - Human infection with Trypanosoma cruzi leads to Chagas disease, which presents as several different clinical conditions ranging from an asymptomatic form to a severe dilated cardiomyopathy. Several studies have demonstrated that T cells play a critical role in the development of cardiac pathology, as well as in immunoregulation during chronic disease. However, the mechanisms that drive protective or pathogenic T cell response are not known. We have shown that CD4(+) T cells from chagasic patients preferentially express T cell receptor (TCR) beta chain variable region (Vbeta) 5. The aim of this work was to determine whether T cells expressing this particular Vbeta region displayed variable or restricted CDR3 sequences, as an indicator of the nature of the stimulus leading to the activation of these T cells in vivo. Additionally, we aimed to evaluate phenotypic characteristics of these cells that might be associated with pathology. CDR3 junctional region sequencing of Vbeta5.1 expressing CD4(+) T cells revealed the occurrence of a highly homologous CDR3 region with conserved TCR Jbeta region usage among patients with cardiac, but not indeterminate, Chagas disease. Moreover, correlation analysis indicated that the frequency of CD4(+)Vbeta5.1(+) cells is associated with granzyme A expression, suggesting that these cells might display cytotoxic function. Together these results provide new insight into T cell recognition of antigens involved in Chagas disease and suggest that these cells may be implicated in the pathogenesis of chagasic cardiomyopathy. PMID- 22774986 TI - Effect of hypoxia and dexamethasone on inflammation and ion transporter function in pulmonary cells. AB - Dexamethasone has been found to reduce the incidence of high-altitude pulmonary oedema. Mechanisms explaining this effect still remain unclear. We assessed the effect of dexamethasone using established cell lines, including rat alveolar epithelial cells (AEC), pulmonary artery endothelial cells (RPAEC) and alveolar macrophages (MAC), in an environment of low oxygen, simulating a condition of alveolar hypoxia as found at high altitude. Inflammatory mediators and ion transporter expression were quantified. Based on earlier results, we hypothesized that hypoxic conditions trigger inflammation. AEC, RPAEC and MAC, pre-incubated for 1 h with or without dexamethasone (10(-7) mol/l), were subsequently exposed to mild hypoxia (5% O(2), or normoxia as control) for 24 h. mRNA and protein levels of cytokine-induced neutrophil chemoattractant-1, monocyte chemoattractant protein-1 and interleukin-6 were analysed. mRNA expression and functional activity of the apical epithelial sodium channel and basolateral Na(+)/K(+) ATPase were determined using radioactive marker ions. In all three types of pulmonary cells hypoxic conditions led to an attenuated secretion of inflammatory mediators, which was even more pronounced in dexamethasone pretreated samples. Function of Na(+)/K(+)-ATPase was not significantly influenced by hypoxia or dexamethasone, while activity of epithelial sodium channels was decreased under hypoxic conditions. When pre-incubated with dexamethasone, however, transporter activity was partially maintained. These findings illustrate that long-term hypoxia does not trigger an inflammatory response. The ion transport across apical epithelial sodium channels under hypoxic conditions is ameliorated in cells treated with dexamethasone. PMID- 22774987 TI - Short wheat challenge is a reproducible in-vivo assay to detect immune response to gluten. AB - It has been reported that interferon (IFN)-gamma-secreting T cells reactive to gluten can be detected in the peripheral blood of individuals with treated coeliac disease (CD) after a short consumption of wheat-containing food. By contrast, very little is known about the reproducibility of this in-vivo procedure in the same patient cohort which underwent two, or more, gluten consumptions. Fourteen coeliac patients in remission consumed wheat bread for 3 days; 13 underwent a second gluten challenge after a wash-out of 3-10 months on a strict gluten-free diet. Immune reactivity to gluten was analysed in peripheral blood by detecting IFN-gamma before and 6 days after commencing a gluten diet. Gliadin-specific IFN-gamma-secreting CD4(+) T cells increased significantly on day 6 of the first challenge. These cells resulted as prevalently human leucocyte antigen (HLA)-DQ restricted and with a phenotype of gut homing, as suggested by the expression of beta7-integrin. Similarly, reactiveness to gliadin was observed after the second wheat consumption, although with an individual variability of responses at each challenge. Our findings confirmed that the short wheat challenge is a non-invasive approach to investigate the gluten-related immune response in peripheral blood of subjects intolerant to gluten. Furthermore, we demonstrated that the in-vivo procedure can be reproduced in the same subject cohort after a gluten wash-out of at least 3 months. Our study has important implications for the application of this procedure to clinical practice. PMID- 22774988 TI - Altered immunoregulatory profile during anti-tumour necrosis factor treatment of patients with inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) can be treated effectively by anti-tumour necrosis factor (TNF) therapy. We set out to investigate the unclear immunoregulatory mechanisms of the treatment. Thirty-four patients with IBD treated with anti-TNF were included. Lymphocytes from peripheral blood and intestinal biopsies were analysed by flow cytometry. Regulation of antigen stimulated proliferation was analysed by blocking of interleukin (IL)-10, transforming growth factor (TGF)-beta or depletion of CD25(+) cells in peripheral blood mononuclear cell cultures. No changes in CD4(+)CD25(+), CD25(+)TNF-RII(+) or CD4(+)CD25(+) forkhead box protein 3 (FoxP3(+)) T cells could be observed in peripheral blood after, in comparison to before, 6 weeks of treatment. The suppressive ability of CD4(+)CD25(+) cells did not change. There was an initial decrease of CD4(+)CD25(+) cells in intestinal mucosa after 2 weeks of treatment, followed by an increase of these cells from weeks 2 to 6 of treatment (P < 0.05). This was accompanied by an increased percentage of CD69(+) cells among these cells after 6 weeks of treatment compared to before treatment (P < 0.01). There was also an increase of mucosal T helper type1 cells from weeks 2 to 6 (P < 0.05). In addition, CD25(+)TNF-RII(+) cells in the mucosa were decreased after 6 weeks of treatment compared to before treatment (P < 0.05). Before treatment, peripheral blood mononuclear cell baseline proliferation was increased when IL-10 was blocked (P < 0.01), but not after. In CD25(+) cell-depleted cultures proliferation increased after treatment (P < 0.05). Our data indicate that anti TNF treatment leads to an induction of effector T cells. Anti-TNF therapy has no significant impact on regulatory T cells in IBD, although the composition of regulatory T cell subsets may change during treatment. PMID- 22774989 TI - Urinary mannose-binding lectin is a biomarker for predicting the progression of immunoglobulin (Ig)A nephropathy. AB - Complement system activation is associated with immunoglobulin A nephropathy (IgAN) activity and progression. The aim of the present study was to investigate the importance of urinary mannose-binding lectin (MBL), at the time of renal biopsy, for evaluating disease severity and predicting the progression of IgAN. A total of 162 patients with biopsy-proven IgAN were enrolled and 50 healthy individuals were selected as normal controls. Urinary MBL was measured by sandwich enzyme-linked immunosorbent assay (ELISA) and normalized for urinary creatinine concentration. Urinary MBL was significantly higher in IgAN patients than that in normal controls, and elevated as histopathological phenotypes upgraded. Urinary MBL was correlated significantly with the well-known clinical predictors for the prognosis of IgAN; that is, renal function (represented by serum creatinine and estimated glomerular filtration rate), proteinuria and arterial hypertension. Urinary MBL was demonstrated to be correlated with the histopathological parameters which have independent value in predicting renal outcome of IgAN according to the Oxford classification; that is, mesangial hypercellularity, segmental glomerulosclerosis, endocapillary hypercellularity and tubular atrophy/interstitial fibrosis. More importantly, non-remission patients at the end of follow-up had significantly higher levels of urinary MBL compared with patients in remission. In conclusion, urinary MBL can be a reliable non-invasive biomarker for evaluating disease severity and predicting the prognosis of IgAN. This is the first report on this issue. However, our conclusions should be verified further in large-scale studies with long-term follow-up. PMID- 22774990 TI - Macrophage migration inhibitory factor deficiency protects pancreatic islets from cytokine-induced apoptosis in vitro. AB - During pathogenesis of diabetes, pancreatic islets are exposed to high levels of cytokines and other inflammatory mediators that induce deterioration of insulin producing beta cells. Macrophage migration inhibitory factor (MIF) plays a key role in the onset and development of several immunoinflammatory diseases and also controls apoptotic cell death. Because the occurrence of apoptosis plays a pathogenetic role in beta cell death during type 1 diabetes development and MIF is expressed in beta cells, we explored the influence of MIF deficiency on cytokine-induced apoptosis in pancreatic islets. The results indicated clearly that elevated MIF secretion preceded C57BL/6 pancreatic islets death induced by interferon (IFN)-gamma + tumour necrosis factor (TNF)-alpha + interleukin (IL) 1beta. Consequently, MIF-deficient [MIF-knock-out (KO)] pancreatic islets or islet cells showed significant resistance to cytokine-induced death than those isolated from C57BL/6 mice. Furthermore, upon exposure to cytokines pancreatic islets from MIF-KO mice maintained normal insulin expression and produced less cyclooxygenase-2 (COX-2) than those from wild-type C57BL6 mice. The final outcome of cytokine-induced islet apoptosis in islets from wild-type mice was the activation of mitochondrial membrane pore-forming protein Bcl-2-associated X protein and effector caspase 3. In contrast, these apoptotic mediators remained at normal levels in islets from MIF-KO mice suggesting that MIF absence prevented initiation of the mitochondrial apoptotic pathway. Additionally, the protection from apoptosis was also mediated by up-regulation of prosurvival kinase extracellular-regulated kinase 1/2 in MIF-KO islets. These data indicate that MIF is involved in the propagation of pancreatic islets apoptosis probably via nuclear factor-kappaB and mitochondria-related proteins. PMID- 22774991 TI - Inhibitory receptor expression on neonatal immune cells. AB - Neonates are born with quantitative and qualitative defects in both adaptive and innate immune responses. The immune system is regulated by several mechanisms, including the signalling of inhibitory receptors. Increased expression of inhibitory receptors may result in a higher threshold for activation and suppressed function of neonatal cells. The aim of this study was to determine whether the expression of seven inhibitory receptors is increased on neonatal immune cells compared to adult immune cells. In a healthy birth cohort, we examined the expression of seven inhibitory immune receptors on neonatal neutrophils, monocytes, natural killer (NK) cells, CD4(+) and CD8(+)T cells. The expression of leucocyte-associated immunoglobulin (Ig)-like receptor-1 (LAIR-1), signal inhibitory receptor on leucocytes-1 (SIRL-1), CD31, signal-regulatory protein alpha (SIRPalpha), Siglec-9, CD200R, immune receptor expressed on myeloid cells-1 (IREM-1) and the membrane-bound ligand CD200 was studied by flow cytometry on leucocytes in cord blood (n = 14), neonatal venous blood (n = 24) and adult venous blood (n = 22). Expression of LAIR-1, CD31 and CD200 was increased consistently across all neonatal T cell subsets. Neonatal monocytes exhibited decreased expression of LAIR-1 and IREM-1 compared to adults. Furthermore, cord blood and neonatal venous blood samples contained a distinct LAIR-1-positive neutrophil population, which was not detected in adult blood. We demonstrated distinct expression of inhibitory receptors on neonatal peripheral blood immune cells in a healthy birth cohort. This is the first evidence that inhibitory receptors play a role in regulation of the neonatal immune system. Consistently increased inhibitory receptor expression on T cells may be an important mechanism in preventing the development of allergy and autoimmunity. PMID- 22774992 TI - Evaluation of correlation between dose and clinical outcomes in subcutaneous immunoglobulin replacement therapy. AB - The importance of serum immunoglobulin (Ig)G concentration in IgG replacement therapy for primary immunodeficiency diseases is established in certain settings. Generally, IgG is infused via the intravenous (IVIG) or subcutaneous (SCIG) route. For IVIG infusion, published data demonstrate that higher IgG doses and trough levels provide patients with improved protection from infection. The same conclusions are not yet accepted for SCIG; data from two recent Phase III studies and a recent post-hoc analysis, however, suggest the same correlation between higher SCIG dose and serum IgG concentration and decreased incidence of infection seen with IVIG. Other measures of clinical efficacy have not been considered similarly. Thus, combined analyses of these and other published SCIG studies were performed; a full comparison of the 13 studies was, however, limited by non standardized definitions and reporting. Despite these limitations, our analyses indicate that certain clinical outcomes improve at higher SCIG doses and associated higher serum IgG concentrations, and suggest that there might be opportunity to improve patient outcomes via SCIG dose adjustment. PMID- 22774993 TI - Lenalidomide enhancement of human T cell functions in human immunodeficiency virus (HIV)-infected and HIV-negative CD4 T lymphocytopenic patients. AB - Suppressed T cell functions in human immunodeficiency virus (HIV) infection were identified and corrected by lenalidomide in middle-aged HIV-infected patients. Chemotaxis of T cells from HIV-infected men (n = 6, mean 43 years) to sphingosine 1-phosphate (S1P) and CCL21 was significantly lower than that of HIV-negative men (n = 6, mean 41 years), and was enhanced significantly up to control levels by 100 and 1000 nM lenalidomide. Generation of interleukin (IL)-2, but not interferon (IFN)-gamma, by T cells of middle-aged HIV-infected men was significantly lower than that for controls and was increased significantly by 10 1000 nM lenalidomide up to a maximum of more than 300%. CD4 and CD8 T cells isolated from healthy middle-aged men and reconstituted in vitro at a low CD4 : CD8 ratio typical of HIV infection had depressed chemotaxis to S1P, but not CCL21, and generation of IL-2, but not IFN-gamma. Significant enhancement of chemotaxis to S1P and CCL21 was induced by 100-1000 nM lenalidomide only for normal T cells at a low CD4 : CD8 ratio. T cells from HIV-negative middle-aged CD4 T lymphocytopenic patients (n = 3), with a CD4 : CD8 ratio as low as that of HIV-infected patients, had similarly diminished chemotaxis to S1P and CCL21, and depressed generation of IL-2, but not IFN-gamma. Lenalidomide at 30-1000 nM significantly enhanced chemotaxis to S1P and IL-2 generation for T cells from HIV negative CD4 T lymphocytopenic patients as from HIV-infected patients, with less effect on CCL21-elicited chemotaxis and none for IFN-gamma generation. Defects in functions of T cells from middle-aged HIV-infected men are partially attributable to CD4 T lymphocytopenia and are corrected by lenalidomide. PMID- 22774995 TI - Developing a science of infrastructure ecology for sustainable urban systems. PMID- 22774994 TI - Immune responses against islet allografts during tapering of immunosuppression--a pilot study in 5 subjects. AB - Transplantation of isolated islet of Langerhans cells has great potential as a cure for type 1 diabetes but continuous immune suppressive therapy often causes considerable side effects. Tapering of immunosuppression in successfully transplanted patients would lower patients' health risk. To identify immune biomarkers that may prove informative in monitoring tapering, we studied the effect of tapering on islet auto- and alloimmune reactivity in a pilot study in five transplant recipients in vitro. Cytokine responses to the graft were measured using Luminex technology. Avidity of alloreactive cytotoxic T Lymphocytes (CTL) was determined by CD8 blockade. The influence of immunosuppression was mimicked by in vitro replenishment of tacrolimus and MPA, the active metabolite of mycophenolate mofetil. Tapering of tacrolimus was generally followed by decreased C-peptide production. T-cell autoreactivity increased in four out of five patients during tapering. Overall alloreactive CTL precursor frequencies did not change, but their avidity to donor mismatches increased significantly after tapering (P = 0.035). In vitro addition of tacrolimus but not MPA strongly inhibited CTL alloreactivity during tapering and led to a significant shift to anti-inflammatory graft-specific cytokine production. Tapering of immunosuppression is characterized by diverse immune profiles that appear to relate inversely to plasma C-peptide levels. Highly avid allospecific CTLs that are known to associate with rejection increased during tapering, but could be countered by restoring immune suppression in vitro. Immune monitoring studies may help guiding tapering of immunosuppression after islet cell transplantation, even though we do not have formal prove yet that the observed changes reflect direct effects of immune suppression on immunity. PMID- 22774997 TI - Thromboembolism prophylaxis in medical inpatients: effect on outcomes and costs. AB - OBJECTIVES: To evaluate the real-world use of venous thromboembolism (VTE) prophylaxis among medical inpatients and the impact of VTE prophylaxis on outcomes and cost. STUDY DESIGN: Retrospective analysis of patientlevel administrative claims data for medical inpatients at risk of VTE and linked outpatient data. METHODS: Data were analyzed from patients admitted to the hospital from 2005 to 2007 (calendar years) with a primary diagnosis of chronic heart failure, thromboembolic stroke, severe lung disease, acute infection, or cancer (index hospitalization), according to whether they received VTE prophylaxis or not. The number of VTE events, time to VTE event, length of hospital stay, and number of major or minor bleeding events were analyzed from the index date until the end of follow-up (180 days postdischarge) or death. RESULTS: Overall, 7127 of 13,293 patients (53.6%) received VTE prophylaxis. Prophylaxis significantly reduced the incidence of VTE compared with no prophylaxis (0.06% vs 3.44%, respectively; P <.00001) and increased the median time to VTE (182 vs 27 days, respectively). Prophylaxis also significantly reduced the incidence of VTE in the 180 days postdischarge. Readmission rates were similar between groups. Major bleeding occurred in 1.57% of patients receiving low molecular weight heparin + warfarin versus <.6% receiving any other form of prophylaxis. The development of VTE or major or minor bleeding events significantly increased total medical costs versus no VTE events (P <.0001) or no bleeding events (P <.0003). CONCLUSIONS: This real-world analysis showed that thromboprophylaxis was underutilized in medical patients, even though the clinical and economic impact of VTE was significant. PMID- 22774996 TI - Urocortin 3 elevates cytosolic calcium in nucleus ambiguus neurons. AB - Urocortin 3 (also known as stresscopin) is an endogenous ligand for the corticotropin-releasing factor receptor 2 (CRF(2)). Despite predominant G(s) coupling of CRF(2), promiscuous coupling with other G proteins has been also associated with the activation of this receptor. As urocortin 3 has been involved in central cardiovascular regulation at hypothalamic and medullary sites, we examined its cellular effects on cardiac vagal neurons of nucleus ambiguus, a key area for the autonomic control of heart rate. Urocortin 3 (1 nM-1000 nM) induced a concentration-dependent increase in cytosolic Ca(2+) concentration that was blocked by the CRF(2) antagonist K41498. In the case of two consecutive treatments with urocortin 3, the second urocortin 3-induced Ca(2+) response was reduced, indicating receptor desensitization. The effect of urocortin 3 was abolished by pre-treatment with pertussis toxin and by inhibition of phospolipase C with U-73122. Urocortin 3 activated Ca(2+) influx via voltage-gated P/Q-type channels as well as Ca(2+) release from endoplasmic reticulum. Urocortin 3 promoted Ca(2+) release via inositol 1,4,5 trisphosphate receptors, but not ryanodine receptors. Our results indicate a novel Ca(2+) -mobilizing effect of urocortin 3 in vagal pre-ganglionic neurons of nucleus ambiguus, providing a cellular mechanism for a previously reported role for this peptide in parasympathetic cardiac regulation. PMID- 22774999 TI - Automating care quality measurement with health information technology. AB - OBJECTIVES: To assess the performance of a health information technology platform that enables automated measurement of asthma care quality using comprehensive electronic medical record (EMR) data, including providers' free-text notes. STUDY DESIGN: Retrospective data study of outpatient asthma care in Kaiser Permanente Northwest (KPNW), a midsized health maintenance organization (HMO), and OCHIN, Inc, a group of Federally Qualified Health Centers. METHODS: We created 22 automated quality measures addressing guideline-recommended outpatient asthma care. We included EMRs of asthma patients aged >12 years during a 3-year observation window and narrowed this group to those with persistent asthma (13,918 KPNW; 1825 OCHIN). We validated our automated quality measures using chart review for 818 randomly selected patients, stratified by age and sex for each health system. In both health systems, we compared the performance of these measures against chart review. RESULTS: Most measures performed well in the KPNW system, where accuracy averaged 88% (95% confidence interval [CI] 82%-93%). Mean sensitivity was 77% (95% CI 62%-92%) and mean specificity was 84% (95% CI 75% 93%). The automated analysis was less accurate at OCHIN, where mean accuracy was 80% (95% CI 72%-89%) with mean sensitivity and specificity 52% (95% CI 35%-69%) and 82% (95% CI 69%-95%) respectively. CONCLUSIONS: To achieve comprehensive quality measurement in many clinical domains, the capacity to analyze text clinical notes is required. The automated measures performed well in the HMO, where practice is more standardized. The measures need to be refined for health systems with more diversity in clinical practice, patient populations, and setting. PMID- 22774998 TI - Racial disparities in lipid control in patients with diabetes. AB - OBJECTIVES: To describe lipid management over time in a cohort of insured patients with diabetes and evaluate differences between African American and white patients. STUDY DESIGN: Automated claims data were used to identify a cohort of 11,411 patients with diabetes in 1997 to 1998. Patients were followed through 2007. METHODS: Rates of hypercholesterolemia testing, treatment, and goal attainment were measured annually. Treatment was determined by a claim for lipid lowering agents, and goal attainment was defined as a low-density lipoprotein cholesterol (LDL-C) level <100 mg/dL. RESULTS: During the study period, LDL-C testing increased from 48% to 70% among African American patients and from 61% to 77% among white patients. Treatment with lipid-lowering drugs increased from 23% to 56% among African American patients and 33% to 61% among white patients. The proportion at goal increased from 35% to 76% and from 24% to 59% among white and African American patients, respectively. African American patients were less likely to be tested for LDL-C (odds ratio [OR] 0.79; 95% confidence interval [CI] 0.73-0.86), treated with lipidlowering agents (OR 0.72; 95% CI 0.65-0.80), have their medication dosage altered (OR 0.65; 95% CI 0.59-0.73), or attain LDL-C goal (OR 0.59; 95% CI 0.56-0.63) compared with white patients. CONCLUSIONS: Although rates of LDL-C testing, treatment, and goal attainment improved over time, racial disparities in dyslipidemia management continued to exist. Further studies to determine the causes of differences in management by race are warranted. PMID- 22775000 TI - Role of insurance, income, and affordability in human papillomavirus vaccination. AB - OBJECTIVES: To examine knowledge of and financial barriers to early adoption of human papillomavirus (HPV) vaccination, specifically the role played by insurance, income, and affordability (measured by forgoing or delaying needed medical care due to cost/no insurance). STUDY DESIGN: We used the 2007 California Health Interview Survey. Females aged 18 to 26 years (n = 1840) and parents with daughters aged 8 to 17 years (n = 5765) were analyzed separately. METHODS: Logistic regression models were used with the following dependent variables: (1) heard of the HPV vaccine, (2) received 1 dose only, (3) completed the series, (4) have not previously heard of HPV vaccine but interested in receiving it, and (5) interested and willing to pay $360 for it. RESULTS: Individuals enrolled in private health maintenance organizations (HMOs) were more likely to have heard of the vaccine compared with the uninsured and those enrolled in public HMOs. Young adults enrolled in private HMOs were also more likely to have initiated HPV vaccination or completed the series compared with uninsured young adults or those insured in non-HMO plans. Higher income parents were more willing to pay the cost of the vaccine. Forgoing needed care due to costs led to lower odds of initiating HPV vaccination among parents and completing the series among young adults. CONCLUSIONS: Strategies to increase HPV vaccination rates should consider insurance or cost barriers for adults and those with high medical care expenditures. Disparities in receipt of the HPV vaccine are likely to continue without targeted outreach to more vulnerable populations. PMID- 22775001 TI - Polymorphisms in Fas gene is associated with HIV-related lipoatrophy in Thai patients. AB - The present study aimed to evaluate the role of genetic polymorphisms in the emergence of lipoatrophy or lipodystrophy in HIV-infected patients with antiretroviral therapy (ART) in Thailand. Position 455 upstream of the Apolipoprotein C3 gene (ApoC3 T-455C, rs2854116), codon 64 of the Beta3 adrenergic receptor gene (ARbeta3 Tcod64C, rs4994), and position 670 upstream of the Fas gene (Fas A-670G, rs1800682) were genotyped in 829 HIV-infected Thai patients who had started ART. Crude and adjusted incidence rate ratios (IRR) were calculated using Poisson regression. The serum levels of cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also analyzed. Multivariate analysis revealed an association between the Fas -670AA genotype, but not the ApoC3 -455 or ARbeta3 cod64 genotypes, with the incidence of lipoatrophy after adjusting for gender and stavudine (d4T) containing regimens (IRR=1.72, 95% CI=1.20-2.45, p=0.003). However, ApoC3 -455C homozygous patients showed elevated serum levels of triglycerides, while this genotype did not affect serum total cholesterol, HDL, or LDL levels in patients with lipoatrophy or lipodystrophy. In contrast, the ARbeta3 cod64 genotype did not show any significant association with the serum levels of cholesterol, triglycerides, HDL, or LDL. In conclusion, Fas -670AA affected the incidence of lipoatrophy in HIV-1-infected Thai patients, while the ApoC3 -455C allele affected the serum levels of triglycerides. These results confirmed the role of genetics in the development of ART-related metabolic disorders. PMID- 22775002 TI - Comparison of binding ability and location of two mesoporphyrin derivatives in liposomes explored with conventional and site-selective fluorescence spectroscopy. AB - Application of porphyrins as photosensitizers is based on their light-triggered generation of reactive oxygen species (ROS) that may cause oxidative tissue damage and ultimately kill cells. Cellular membranes are the action grounds of many sensitizers due to their hydrophobic or amphiphilic character as well as the location of many of the targets attacked by ROS. Hence, the binding ability and location of porphyrins in liposomes as simple models of cellular membranes are of outstanding interest. Here we compare mesoporphyrin IX dimethyl ester (MPE) and its nonesterified form, mesoporphyrin IX dihydrochloride (MPCl). Monocomponent small unilamellar vesicles formed of various saturated phosphatidylcholines with incorporated mesoporphyrins were investigated. We determined the binding parameters and the inhomogeneous distribution functions (IDFs) by different fluorescence techniques. We found in general that the binding ability of MPE is considerably greater than that of MPCl. In the case of MPCl, the IDFs suggest that only one of the two binding site types identified earlier for MPE ("site II") exists; the other one ("site I") vanishes while a new one appears ("site III"). We can confirm that "site I" is located between the two lipid layers, "site II" is situated between the hydrocarbon chains, while the location of the novel "site III" is along the outer part of the hydrocarbon chains partially inserted between the lipid head groups. PMID- 22775003 TI - Structural mechanism for alteration of collagen gel mechanics by glutaraldehyde crosslinking. AB - Soft collagenous tissues that are loaded in vivo undergo crosslinking during aging and wound healing. Bioprosthetic tissues implanted in vivo are also commonly crosslinked with glutaraldehyde (GA). While crosslinking changes the mechanical properties of the tissue, the nature of the mechanical changes and the underlying microstructural mechanism are poorly understood. In this study, a combined mechanical, biochemical and simulation approach was employed to identify the microstructural mechanism by which crosslinking alters mechanical properties. The model collagenous tissue used was an anisotropic cell-compacted collagen gel, and the model crosslinking agent was monomeric GA. The collagen gels were incrementally crosslinked by either increasing the GA concentration or increasing the crosslinking time. In biaxial loading experiments, increased crosslinking produced (1) decreased strain response to a small equibiaxial preload, with little change in response to subsequent loading and (2) decreased coupling between the fiber and cross-fiber direction. The mechanical trend was found to be better described by the lysine consumption data than by the shrinkage temperature. The biaxial loading of incrementally crosslinked collagen gels was simulated computationally with a previously published network model. Crosslinking was represented by increased fibril stiffness or by increased resistance to fibril rotation. Only the latter produced mechanical trends similar to that observed experimentally. Representing crosslinking as increased fibril stiffness did not reproduce the decreased coupling between the fiber and cross-fiber directions. The study concludes that the mechanical changes in crosslinked collagen gels are caused by the microstructural mechanism of increased resistance to fibril rotation. PMID- 22775005 TI - Comparative effect of lens care solutions on blink rate, ocular discomfort and visual performance. AB - PURPOSE: To help maintain clear vision and ocular surface health, eye blinks occur to distribute natural tears over the ocular surface, especially the corneal surface. Contact lens wearers may suffer from poor vision and dry eye symptoms due to difficulty in lens surface wetting and reduced tear production. Sustained viewing of a computer screen reduces eye blinks and exacerbates such difficulties. The present study evaluated the wetting effect of lens care solutions (LCSs) on blink rate, dry eye symptoms, and vision performance. METHODS: Sixty-five adult habitual soft contact lens wearers were recruited to adapt to different LCSs (Opti-free, ReNu, and ClearCare) in a cross-over design. Blink rate in pictorial viewing and reading (measured with an eyetracker), dry eye symptoms (measured with the Ocular Surface Disease Index questionnaire), and visual discrimination (identifying tumbling E) immediately before and after eye blinks were measured after 2 weeks of adaption to LCS. Repeated measures anova and mixed model ancova were conducted to evaluate effects of LCS on blink rate, symptom score, and discrimination accuracy. RESULTS: Opti-Free resulted in lower dry eye symptoms (p = 0.018) than ClearCare, and lower spontaneous blink rate (measured in picture viewing) than ClearCare (p = 0.014) and ReNu (p = 0.041). In reading, blink rate was higher for ClearCare compared to ReNu (p = 0.026) and control (p = 0.024). Visual discrimination time was longer for the control (daily disposable lens) than for Opti-Free (p = 0.007), ReNu (p = 0.009), and ClearCare (0.013) immediately before the blink. CONCLUSIONS: LCSs differently affected blink rate, subjective dry eye symptoms, and visual discrimination speed. Those with wetting agents led to significantly fewer eye blinks while affording better ocular comfort for contact lens wearers, compared to that without. LCSs with wetting agents also resulted in better visual performance compared to wearing daily disposable contact lenses. These presumably are because of improved tear film quality. PMID- 22775004 TI - Transitions to adulthood: examining the influence of initiation rites on the HIV risk of adolescent girls in Mangochi and Thyolo districts of Malawi. AB - Although some cultural practices have been identified as a determinant of HIV transmission, research investigating how specific practices affect HIV risk is lacking. In Malawi, initiation rites, in which young people attend ceremonies around the time of puberty, have received little attention. In this qualitative study, we explored whether communities in southern Malawi perceive initiation rites to be an HIV risk factor for girls. Twelve focus group discussions were held with adolescents and adults in a rural community of Thyolo district and a peri-urban community of Mangochi district. Community members observed that certain aspects of traditional initiation rites propel girls into sexual roles expected of adulthood, without facilitating their adaption to the emerging landscape of HIV, thereby increasing HIV risk. HIV prevention programming needs to address the role of initiation rites in adolescent girls' vulnerability to HIV and help young girls navigate the conflicting messages they receive from a wide range of channels about expected sexual behavior. PMID- 22775006 TI - Urgent endoscopy in severe non-variceal upper gastrointestinal hemorrhage: does the Glasgow-Blatchford score help endoscopists? AB - OBJECTIVE: The Glasgow-Blatchford score (GBS) has been validated to select severe patients with non-variceal upper gastrointestinal hemorrhage (UGIH). The aim was to compare the yield of the triage based on the GBS with an endoscopist' decision to perform an urgent upper gastrointestinal endoscopy (UGIE) in newly admitted patients and inpatients with UGIH in the setting of an endoscopy on-duty service in 13 tertiary care centers. MATERIAL AND METHODS: During a 6-month period, GBS and patient data were collected for all patients with non-variceal UGIH for whom an UGIE was requested in emergency. If patients experienced severe endoscopic lesion, surgery or death, they were categorized as patients who had been at need for urgent UGIE. RESULTS: The 102 UGIH patients included (mean age 62, men 73%) had a median GBS of 12 (range 0-21), significantly lower for new patients compared with inpatients (11, range 0-21 vs. 14, range 2-21, respectively, p = 0.001). If triage for urgent UGIE had followed the GBS, no more patients would have had an urgent UGIE compared with what endoscopists performed (99/102 (97%) vs. 92/102 (90%), respectively, p = 0.09). Sensitivity for the detection of patients who needed an UGIE was no different with the GBS than endoscopists (98% vs. 98%, respectively, p = 0.10) and both showed insufficient specificity (4% and 19%, respectively). CONCLUSIONS: The GBS does not detect more patients at need for urgent UGIE than on-duty endoscopists. Both methods lead to numerous unjustified UGIEs. A score that would equally help endoscopists in their decision to intervene urgently is still warranted. PMID- 22775008 TI - Characterization and application of calcium-dependent beta-propeller phytase from Bacillus amyloliquefaciens DS11. AB - The enzyme phytase has broad biotechnological applications, especially in the reduction of phytate, antinutritional factors that chelate essential minerals, in human and animal food. We investigated the enzymatic properties of beta-propeller phytase (BPP) from Bacillus amyloliquefaciens DS11. Thermal refolding analysis demonstrated that BPP can remarkably restore its enzymatic activity in the presence of 5 mM Ca(2+) to 87% of its original activity after heating to 100 degrees C and subsequent cooling, indicating that the enzyme requires Ca(2+) for appropriate refolding. Furthermore, pH-dependent kinetic studies showed that BPP required excess Ca(2+) for its enzymatic activity as the pH decreased, suggesting that the optimal Ca(2+)-phytate ratio for enzymatic catalysis depends on the pH value of the environment. Finally, we verified the practical application of BPP at two different pH's using soybean meal as a natural source of phytate. As compared to a commercial phytase, BPP efficiently hydrolyzed food phytate over neutral pH ranges. PMID- 22775057 TI - Health care in adults with Down syndrome: a longitudinal cohort study. AB - BACKGROUND: Individuals with Down syndrome increasingly survive into adulthood, yet little is known about their healthcare patterns as adults. Our study sought to characterise patterns of health care among adults with Down syndrome based on whether they had fully transitioned to adult-oriented providers by their inception in this cohort. METHODS: In this retrospective observational cohort study, healthcare utilisation and annualised patient charges were evaluated in patients with Down syndrome aged 18-45 years who received care in a single academic health centre from 2000 to 2008. Comparisons were made based on patients' provider mix (only adult-focused or 'mixed' child- and adult-focused providers). RESULTS: The cohort included 205 patients with median index age = 28 years; 52% of these adult patients had incompletely transitioned to adult providers and received components of their care from child-focused providers. A higher proportion of these 'mixed' patients were seen exclusively by subspecialty providers (mixed = 81%, adult = 46%, P < 0.001), suggesting a need for higher intensity specialised services. Patients in the mixed provider group incurred higher annualised charges in analyses adjusted for age, mortality, total annualised encounters, and number of subspecialty disciplines accessed. These differences were most pronounced when stratified by whether patients were hospitalised during the study period (e.g., difference in adjusted means between mixed versus adult provider groups: $571 without hospitalisation, $19,061 with hospitalisation). CONCLUSIONS: In this unique longitudinal cohort of over 200 adults aged 18-45 years with Down syndrome, over half demonstrated incomplete transition to adult care. Persistent use of child-focused care, often with a subspecialty emphasis, has implications for healthcare charges. Future studies must identify reasons for distinct care patterns, examine their relationship with clinical outcomes, and evaluate which provider types deliver the highest quality care for adults with Down syndrome and a wide variety of comorbidities. PMID- 22775058 TI - Selective and regulated gene expression in murine Purkinje cells by in utero electroporation. AB - Cerebellar Purkinje cells, which convey the only output from the cerebellar cortex, play an essential role in cerebellar functions, such as motor coordination and motor learning. To understand how Purkinje cells develop and function in the mature cerebellum, an efficient method for molecularly perturbing them is needed. Here we demonstrate that Purkinje cell progenitors at embryonic day (E)11.5 could be efficiently and preferentially transfected by spatially directed in utero electroporation (IUE) with an optimized arrangement of electrodes. Electrophysiological analyses indicated that the electroporated Purkinje cells maintained normal membrane properties, synaptic responses and synaptic plasticity at postnatal days 25-28. By combining the L7 promoter and inducible Cre/loxP system with IUE, transgenes were expressed even more specifically in Purkinje cells and in a temporally controlled manner. We also show that three different fluorescent proteins could be simultaneously expressed, and that Bassoon, a large synaptic protein, could be expressed in the electroporated Purkinje cells. Moreover, phenotypes of staggerer mutant mice, which have a deletion in the gene encoding retinoid-related orphan receptor alpha (RORalpha1), were recapitulated by electroporating a dominant-negative form of RORalpha1 into Purkinje cells at E11.5. Together, these results indicate that this new IUE protocol, which allows the selective, effective and temporally regulated expression of multiple foreign genes transfected into Purkinje cell progenitors in vivo, without changing the cells' physiological characteristics, is a powerful tool for elucidating the molecular mechanisms underlying early Purkinje cell developmental events, such as dendritogenesis and migration, and synaptic plasticity in mature Purkinje cells. PMID- 22775059 TI - Kinetic evaluation of removal of odorous contaminants in a three-stage biological air filter. AB - Biofiltration is a cost-effective technology for removing air contaminants from animal facilities. Kinetic analysis can be helpful in understanding and designing the process but has not been performed on full-scale filters treating complex mixtures. In this study, kinetics was investigated in a full-scale biological filter treating air pollutants from a pig facility. Due to the high air flow rates used in the filter, both a plug flow model and a model based on complete mixing were tested with respect to kinetic order and Michaelis-Menten kinetics. Application of these models only gave poor to moderate agreement with air filter removal data. Two alternative kinetic models (Stover-Kincannon model and Grau second-order model) adopted from wastewater biofiltration process analysis were introduced to analyze contaminant removal in the biological air filter. Data analysis demonstrated the applicability of these two models with a high degree of precision on contaminant removal in the biological air filter. Whereas the Stover Kincannon model demonstrated that pollutant removal rates were related to the mass loading rates, the Grau second-order kinetic model indicated that the removal efficiencies were dependent on air loading rates. Therefore, the kinetic data can be used for comparing biofilter performances and for design purposes. PMID- 22775060 TI - Clinical prediction in group psychotherapy. AB - Prior research in individual therapy has provided evidence that therapists are poor predictors of client outcome and often misjudge clients' perceptions of the therapeutic relationship. The focus of the current research was to conduct a similar predictive study in a group setting. Group therapists were recruited from a university counseling center and a state psychiatric hospital; 64 group members and 10 group leaders participated in the study. We tested therapist accuracy in predicting client outcome and perceived quality of therapeutic relationship. Results suggested that therapists underestimate the number of clients who deteriorate during therapy and were unable to accurately predict client perceptions of the group relationship, replicating findings from larger samples in the individual literature. Results suggest that using outcome and process measures as feedback tools may be also useful for clinicians leading groups. PMID- 22775061 TI - Oxidation-resistant acidic resins prepared by partial carbonization as cocatalysts in synthesis of adipic acid. AB - The oxidation-resistant acidic resins are of great importance for the catalytic oxidation systems. In this paper, the oxidatively stable acidic resins are obtained from the cation ion exchange resins (CIERs) through the thermal treatment in N(2) atmosphere. The structure and properties of the thermally treated CIERs were characterized by chemical analysis, Fourier transform infrared (FT-IR) spectra, acid capacity measurement and scanning electron microscope (SEM). The thermally treated CIERs possess high acid capacity up to 4.09 mmol g( 1). A partial carbonization is observed in the thermal treatment process of CIERs, but the morphology of resin spheres maintains well. The as-prepared CIERs are used as solid acids to assist the hydrogen peroxide oxidation of cyclohexene to adipic acid (ADA) with tungstic acid as the catalyst precursor. The improved yields of ADA in the recycling reaction are obtained in the presence of acidic CIERs. Meanwhile, the unproductive decomposition of H(2)O(2) is effectively suppressed. The high yields of ADA (about 81%) are kept by the thermally treated CIERs even after the fifth cycle. The thermally treated CIERs exhibit excellent acid-catalytic performance and possess remarkable oxidation-resistant capability. PMID- 22775062 TI - Effect of hyperbaric oxygen on Vibrio vulnificus and murine infection caused by it. AB - Vibrio vulnificus is a bacterium known to cause fatal necrotizing soft tissue infection in humans. Here, a remarkable therapeutic effect of hyperbaric oxygen (HBO) on V. vulnificus infection provoked by its injection into mouse footpads is described. HBO was shown to be bactericidal to this bacterium in vitro as well as in the infected tissue. The bactericidal activity of HBO was shown to be due to reactive oxygen species (ROS), the efficacy of HBO against V. vulnificus infection being accounted for by the high sensitivity of this bacterium to ROS. Besides being somewhat weak in ROS-inactivating enzyme activities, this bacterium is also unusually sensitive to ultraviolet light and other DNA-damaging agents. It seems likely that the sensitivity of V. vulnificus to HBO is mainly due to its poor ability to repair oxidative damage to DNA. These findings encourage clinical application of HBO against potentially fatal V. vulnificus infection in humans. PMID- 22775063 TI - Clinical and histological evaluation of subepithelial connective tissue after collagen sponge implantation in the human palate. AB - BACKGROUND AND OBJECTIVE: Successful root-coverage treatment depends on the thickness of the donor tissue. This study aimed to evaluate the thickness of donor tissue after augmentation of the connective tissue in the palatal area by implantation of lyophilized collagen sponge (Hemospon((r)) ). MATERIAL AND METHODS: Ten patients with an indication for root coverage, whose palate was deficient in adequate connective tissue, were recruited. The procedure was carried out in two stages. In the first stage, the palatal thickness in the donor site was measured at three standardized points (points 1, 2 and 3), from the distal of the canine to the distal of the first molar, and the lyophilized collagen sponge was inserted. In the second stage, the palatal thickness over the implant was measured (at points 1, 2 and 3), two biopsies of the palatal mucosa were collected - one over the implant (experimental sample) and the other on the contralateral side (control sample) - and then root-coverage treatment was performed. Analyses consisted of clinical assessment of the palatal measurements before and after sponge implantation, and histological assessment of the experimental and control biopsy samples. Data were analyzed using the Wilcoxon test. RESULTS: Both analyses showed a significant increase in mean thickness, of 1.08 mm of neoformed tissue in the clinical analysis (the tissue at point 2 was the thickest of the three points) and of 0.53 mm in the histological analysis. CONCLUSION: The insertion of lyophilized collagen sponge induced a significant increase in the thickness of palatal connective tissue. PMID- 22775064 TI - Evaluation of tourists' UV exposure in Paris. AB - BACKGROUND: Ultraviolet (UV) exposure is one of the most important risk factor for skin cancers. If UV hazard has been evaluated in tropical countries or in some population - children, outdoor activities - little information is available about UV hazard in high latitude towns like Paris, considered as the most 'charismatic city' in the world. OBJECTIVE: To evaluate UV exposure in Paris in spring, in sun and shade, in real life conditions. METHODS: We evaluated erythemal UV exposure, during four sunny days in May-June in eight Paris touristic sites during peak hours (2 days), and during two walks in touristic downtown of Paris. Measures were performed in sun and shade. UV radiation exposure was evaluated with UV index performed with a 'Solarmeter ultraviolet index (UVI)' and UV dose with 'standard erythema dose' (SED) and 'minimal erythema dose' (MED) calculations. RESULTS: Despite 'average' UVI in sunny conditions, a 4-h sun exposure reaches 13-20 SED and 3-10 MED according to phototype. Clouds were inefficient to protect against UV. Shade of places reduces moderately UVI (50-60%) in forecourts. Exposure during 1-h walk reach at least one MED in real life conditions for skin phototypes I-IV. CONCLUSIONS: UV risk for tourist is quite high in spring in Paris. UVI remains high despite high cloud fraction. Shade reduces UVI, but UV protection factor is only 2-3 in large places such as Place Notre Dame and Place Charles de Gaulle. So sun protection campaigns should be proposed, and sun protective strategies could be integrated in urban planning. PMID- 22775065 TI - Evaluation of ocular manifestations and blindness in HIV/AIDS patients in a tertiary care hospital in South India. AB - PURPOSE: To report the prevalence of ocular manifestations in patients with HIV/AIDS and their correlation with the clinical stage of disease as well as the CD4 cell count. METHODS: 100 HIV-positive patients, who presented to a tertiary care hospital, were included. The WHO clinical staging of HIV/AIDS, CD4 count, duration of disease, and presence and type of ocular manifestations were noted. RESULTS: Overall, 46 patients (46%) had ocular manifestations related to HIV/AIDS. The most common manifestations were HIV retinopathy (12%) and cytomegalovirus (CMV) retinitis (7%). The prevalence of ocular manifestations correlated significantly with the WHO clinical stages 3 and 4 of HIV/AIDS (p = .001) and with low CD4 count (p = .001). CONCLUSIONS: CD4 cell counts and WHO clinical stage of HIV disease are important predictors for the occurrence of ocular morbidity in HIV-positive individuals. Routine comprehensive ophthalmic screening and appropriate initiation of therapy in these patients can potentially decrease ocular morbidity. PMID- 22775066 TI - Community perspectives on parental influence on engagement in multiple concurrent sexual partnerships among youth in Tanzania: implications for HIV prevention programming. AB - Although concurrent sexual partnerships (CPs) have been hypothesized to be an important risk factor for HIV in sub-Saharan Africa, the social and cultural factors that encourage CPs are not well understood. This study explored the community's perspectives on the role that parents can play in influencing their children's decision to engage in CPs. We conducted 16 in-depth interviews, 32 focus group discussions, and 16 key informant interviews with 280 adult participants in Tanzania. Data were coded; findings and conclusions were developed based on themes that emerged from coding. Three parental influences on CPs emerged: parent-child communication about sex, both silent and explicit encouragement of CPs, and parental behavior modeling. Parents are typically either too busy or too "embarrassed" to talk with their children about sex and CPs. The information parents do give is often confusing, fear-based, inadequate, and/or only focused on daughters. Parents themselves also encourage CPs through complicity of silence when their daughters come home with extra cash or consumer goods. In some cases, parents overtly encourage their children, particularly daughters, to practice CPs due to the promise of money from wealthy partners. Finally, when parents engage in CPs, the children themselves learn to behave similarly. These results suggest that parents can influence their children's decision to engage in CPs. HIV prevention interventions should address this by promoting parent-child communication about sexuality; associated disease risks and gender-equitable relationships; promoting positive parental role modeling; and educating parents on the implications of encouragement of CPs in their children. PMID- 22775068 TI - Luminescence quantum yield of single gold nanorods. AB - We study the luminescence quantum yield (QY) of single gold nanorods with different aspect ratios and volumes. Compared to gold nanospheres, we observe an increase of QY by about an order of magnitude for particles with a plasmon resonance >650 nm. The observed trend in QY is further confirmed by controlled reshaping of a single gold nanorod to a spherelike shape. Moreover, we identify two spectral components, one around 500 nm originating from a combination of interband transitions and the transverse plasmon and one coinciding with the longitudinal plasmon band. These components are analyzed by correlating scattering and luminescence spectra of single nanorods and performing polarization sensitive measurements. Our study contributes to the understanding of luminescence from gold nanorods. The enhanced QY we report can benefit applications in biological and soft matter studies. PMID- 22775069 TI - Risk: benefit of treating high blood pressure in older adults. AB - Older people (those aged 65 years or over) comprise over 15% of the UK's population and this cohort is growing. Whilst at greatest risk from systemic arterial hypertension (hypertension), its resultant end organ damage and clinically significant cardiovascular disease, this group was initially neglected in clinical trials and thereby denied treatment, with the lack of evidence cited as justification. However since the 1960s, when the first landmark trials in severe diastolic hypertension were published, there has been a progressive attempt to understand the pathophysiology of hypertension and to expand the evidence base for treatment in older adults. In contrast to the participants of the very first randomized trials who had a mean age of 51 years, the recent Hypertension in the Very Elderly Trial demonstrated significant mortality and morbidity benefits from the treatment of both mixed systolic and diastolic hypertension, as well as isolated systolic hypertension in octogenarians. This review highlights the progressive evidence base behind the relative risks and benefits of treating hypertension in older adults. PMID- 22775070 TI - Computer-related visual symptoms in office workers. AB - PURPOSE: Many individuals report visual symptoms during office work and specifically computer use. This study determined the prevalence of symptoms in a population of office workers, and examined the association between these symptoms and both dry eye disease and other demographic factors. METHOD: A written questionnaire was used to quantify the prevalence of symptoms in 520 New York City office workers, and to determine the effect of risk factors including gender, ethnicity, age, smoking, type of refractive correction and hours spent doing computer work. The questionnaire also examined the prevalence of ocular surface disease. RESULTS: A significant positive correlation was observed between the symptom score and the number of hours spent working on a computer in a typical day. The most prevalent symptom was tired eyes, which was reported by approximately 40% of subjects as occurring 'at least half the time'. 32% and 31% of subjects reported symptoms of dry eye and eye discomfort, respectively. Symptoms varied significantly with gender (being greater in females), ethnicity (being greater in Hispanics) and the use of rewetting drops. A significant positive correlation was observed between computer-related visual symptoms and the Ocular Surface Disease Index (OSDI), a measure of dry eye. CONCLUSIONS: Visual symptoms associated with computer use occur frequently in the general population producing discomfort for extended periods of time. They are strongly associated with ocular surface disease. Therapeutic regimens need to be developed for this widespread condition. PMID- 22775071 TI - Bowling alone, healing together: the role of social capital in delivery reform. PMID- 22775072 TI - Quality care opportunities: refining physician performance measurement in ambulatory care. AB - Accurately measuring the quality of care that ambulatory care physicians provide is an important endeavor. Current measurement instruments, while offering useful information about care systems, remain suboptimal for the measurement of individual physician performance. We offer the quality care opportunities model of ambulatory care physician performance measurement, which may address issues with current instruments while also offering useful information about efficiency and productivity for individual physicians and delivery systems from a patient centered perspective. PMID- 22775073 TI - Unintended consequences of a quality measure for acute bronchitis. AB - OBJECTIVES: To determine whether diagnostic coding shifts might undermine apparent improvements resulting from the 2007 Healthcare Effectiveness Data and Information Set (HEDIS) measure on avoidance of antibiotics for the treatment of adults with acute bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 466.0). STUDY DESIGN: Time series analysis within a primary care network for 3 successive winter seasons from 2006 to 2009. METHODS: All initial adult visits with a primary diagnosis code of 466.0 or 490 (bronchitis, not otherwise specified) were analyzed. Multivariable analysis accounted for clustering of observations by physician. RESULTS: The percentage of visits treated with antibiotics declined significantly for code 466.0 (76.8% to 74.4% to 27.0% of visits over the 3-year study period; P <.0001 for trend) but did not decline for code 490 (86.6% to 87.6% to 82.1% of visits; P = .33 for trend). Use of the 490 code rose significantly over the study period, from 1.5% of total bronchitis visits in year 1 to 84.6% of total bronchitis visits in year 3. As a result, the odds of an antibiotic prescription for codes 466 and 490 combined decreased slightly in year 3 compared with year 1 (odds ratio 0.88; 95% confidence interval 0.78-0.99). CONCLUSIONS: While performance on the specific HEDIS measure improved dramatically during this study period, overall antibiotic prescribing did not decline substantially. Quality measures that assess performance on specific diagnosis codes are imperfect and do not account for shifts in diagnosis coding. PMID- 22775074 TI - Impact of positive airway pressure among obstructive sleep apnea patients. AB - OBJECTIVES: To evaluate the clinical and economic impact of positive airway pressure (PAP) among patients with obstructive sleep apnea (OSA). STUDY DESIGN: Retrospective claims-based analysis of OSA patients diagnosed with polysomnography (PSG) between January 1, 2005, and April 30, 2008. METHODS: Patients were required to have 2 or more claims for OSA diagnosis within 1 year after their first PSG test, and a minimum of 12 months' baseline and 24 months' follow-up continuous health plan enrollment. Patients with pulmonary disease or PAP use before the first PSG test were excluded. Outcomes included all-cause and sleep apnea-related hospitalization and healthcare costs. Multivariable analyses were performed to adjust for baseline characteristics. RESULTS: Of the 15,424 patients identified, 90.7% used PAP and 9.3% did not. The PAP group had lower all cause (19.0% vs 24.2%, P <.001) and sleep apnea-related (8.0% vs 11.3%, P <.001) hospitalization rates than the non-PAP group during the follow-up period. After adjusting for baseline characteristics, patients in the PAP group were less likely to have an all-cause (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.61-0.80]) or sleep apnea-related (OR 0.69; 95% CI 0.58-0.83) hospitalization than non-PAP patients. PAP users on average incurred 10% lower all-cause costs than non-PAP patients ($705 per member per month vs $786 per member per month, P <.001) in multivariable analysis. CONCLUSIONS: Among OSA patients in real-world practice, PAP users had significantly lower hospitalization risks and all-cause healthcare costs. PMID- 22775075 TI - Barriers to transition of obese patients from hospital to community. AB - OBJECTIVES: To identify barriers encountered by case managers in hospitals, home care agencies, and nursing homes in the transition of the obese patient from the hospital to the community. STUDY DESIGN: Exploratory descriptive design was used. Hospital case managers, nursing home administrators, and Medicare-certified home healthcare agency administrators were surveyed to identify barriers. METHODS: Hospital case managers in each licensed acute care hospital, directors of licensed nursing homes, and administrators of the Medicarecertified home healthcare agencies in 1 southern state were surveyed. The survey instrument was designed by the investigators based on variables identified in the literature or encountered within their practice. Instruments consisted of items related to the respondent's experience with barriers such as patient size, degree of patient independence, patient care requirements, staffing levels, and the need for assistive equipment, as well as items used to collect basic demographic information. RESULTS: Both hospital case managers and nursing home directors reported as major barriers the equipment, the size of the patient, patient independence, and finances. Home care agency directors reported that the presence or absence of a competent caregiver was the major factor in the decision to accept or not accept an obese patient. CONCLUSIONS: Transition of the obese patient presents major challenges. Further exploration is needed to identify the extent of problems and make policy recommendations toward a solution. PMID- 22775076 TI - The impact and control of biofouling in marine aquaculture: a review. AB - Biofouling in marine aquaculture is a specific problem where both the target culture species and/or infrastructure are exposed to a diverse array of fouling organisms, with significant production impacts. In shellfish aquaculture the key impact is the direct fouling of stock causing physical damage, mechanical interference, biological competition and environmental modification, while infrastructure is also impacted. In contrast, the key impact in finfish aquaculture is the fouling of infrastructure which restricts water exchange, increases disease risk and causes deformation of cages and structures. Consequently, the economic costs associated with biofouling control are substantial. Conservative estimates are consistently between 5-10% of production costs (equivalent to US$ 1.5 to 3 billion yr(-1)), illustrating the need for effective mitigation methods and technologies. The control of biofouling in aquaculture is achieved through the avoidance of natural recruitment, physical removal and the use of antifoulants. However, the continued rise and expansion of the aquaculture industry and the increasingly stringent legislation for biocides in food production necessitates the development of innovative antifouling strategies. These must meet environmental, societal, and economic benchmarks while effectively preventing the settlement and growth of resilient multi-species consortia of biofouling organisms. PMID- 22775077 TI - Intercellular cytosolic transfer correlates with mesenchymal stromal cell rescue of umbilical cord blood cell viability during ex vivo expansion. AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSC) have been observed to participate in tissue repair and to have growth-promoting effects on ex vivo co culture with other stem cells. METHODS: In order to evaluate the mechanism of MSC support on ex vivo cultures, we performed co-culture of MSC with umbilical cord blood (UCB) mononuclear cells (MNC) (UCB-MNC). RESULTS: Significant enhancement in cell growth correlating with cell viability was noted with MSC co-culture (defined by double-negative staining for Annexin-V and 7-AAD; P < 0.01). This was associated with significant enhancement of mitochondrial membrane potential (P < 0.01). We postulated that intercellular transfer of cytosolic substances between MSC and UCB-MNC could be one mechanism mediating the support. Using MSC endogenously expressing green fluorescent protein (GFP) or labeled with quantum dots (QD), we performed co-culture of UCB-MNC with these MSC. Transfer of these GFP and QD was observed from MSC to UCB-MNC as early as 24 h post co-culture. Transwell experiments revealed that direct contact between MSC and UCB-MNC was necessary for both transfer and viability support. UCB-MNC tightly adherent to the MSC layer exhibited the most optimal transfer and rescue of cell viability. DNA analysis of the viable, GFP transfer-positive UCB-MNC ruled out MSC transdifferentiation or MSC-UCB fusion. In addition, there was statistical correlation between higher levels of cytosolic transfer and enhanced UCB-MNC viability (P < 0.0001). CONCLUSIONS: Collectively, the data suggest that intercellular transfer of cytosolic materials could be one novel mechanism for preventing UCB cell death in MSC co-culture. PMID- 22775115 TI - High levels of alpha-tocopherol in Norwegian alpine grazing plants. AB - Antioxidants prevent oxidation of fatty acids in milk and meat. In the present study, the content of tocopherol antioxidants (vitamin E) in vegetative and reproductive parts of 22 grazing plants was estimated in two alpine areas used for summer farming. The overall mean content of alpha-tocopherol was 135 +/- 34 MUg g(-1) DW, and grasses had much lower content (28 +/- 11 MUg g(-1) DW) than herbs (215 +/- 94 MUg g(-1) DW), sedges (186 +/- 78 MUg g(-1) DW), and woody species (178 +/- 52 MUg g(-1) DW). Highest and lowest species-specific levels were 649 +/- 91 and 2 +/- 1 MUg g(-1) DW, respectively. Plants from light and shady habitats did not differ in their alpha-tocopherol content, which was idiosyncratic as indicated by significant interactions between species, sampling occasion, site, and tissue type. Our results show that alpine ranges provide fodder with high levels of alpha-tocopherol. PMID- 22775116 TI - Assessing sustainability in real urban systems: the Greater Cincinnati Metropolitan Area in Ohio, Kentucky, and Indiana. AB - Urban systems have a number of factors (i.e., economic, social, and environmental) that can potentially impact growth, change, and transition. As such, assessing and managing these systems is a complex challenge. While, tracking trends of key variables may provide some insight, identifying the critical characteristics that truly impact the dynamic behavior of these systems is difficult. As an integrated approach to evaluate real urban systems, this work contributes to the research on scientific techniques for assessing sustainability. Specifically, it proposes a practical methodology based on the estimation of dynamic order, for identifying stable and unstable periods of sustainable or unsustainable trends with Fisher Information (FI) metric. As a test case, the dynamic behavior of the City, Suburbs, and Metropolitan Statistical Area (MSA) of Cincinnati was evaluated by using 29 social and 11 economic variables to characterize each system from 1970 to 2009. Air quality variables were also selected to describe the MSA's environmental component (1980 2009). Results indicate systems dynamic started to change from about 1995 for the social variables and about 2000 for the economic and environmental characteristics. PMID- 22775078 TI - Evaluation of very high- and very low-dose intravitreal aflibercept in patients with neovascular age-related macular degeneration. AB - PURPOSE: To determine bioactivity and duration of effect of intravitreal aflibercept injection (also known as vascular endothelial growth factor Trap-Eye) for neovascular age-related macular degeneration (AMD). METHODS: In this double masked, phase 1 study, 28 patients with lesions <=12 disc areas, >=50% active choroidal neovascularization (CNV), and best corrected visual acuity (BCVA) <=20/40 were randomized 1:1 to a single intravitreal injection of aflibercept 0.15 or 4 mg. The primary end point was the change from baseline in central retinal/lesion thickness (CR/LT) at week-8. Secondary outcomes were the change from baseline BCVA, the change in CNV lesion size and area of leakage, and proportion of patients requiring repeat injection at 8 weeks. RESULTS: Mean percent decrease in CR/LT for the 4-mg and 0.15-mg groups was, respectively, 34.2 versus 13.3 at week 4 (P=0.0065), 23.8 versus 5.9 at week 6 (P=0.0380), and 25.2% versus 11.3% at week 8 (P=0.150). The 4-mg group gained a mean of 4.5 letters in BCVA (6/14 patients gaining >=10 letters) versus 1.1 letters in 0.15-mg group (1/14 gaining >=10 letters) at week 8. Fewer patients needed retreatment in the 4 mg group at week 8. No serious adverse event or ocular inflammation was reported in either group. CONCLUSIONS: Intravitreal aflibercept 4 mg had a safety profile similar to that of the very low dose 0.15 mg, and was well-tolerated. The 4-mg dose significantly reduced foveal thickening at weeks 4 and 6, significantly improved BCVA at weeks 6, and reduced the need for repeat injection after 8 weeks compared with intravitreal aflibercept 0.15 mg in neovascular AMD patients. PMID- 22775117 TI - First assessment at home of amyotrophic lateral sclerosis (ALS) patients by a nutrition network in the French region of Limousin. AB - Malnutrition is associated with poor survival among patients with amyotrophic lateral sclerosis (ALS). This study aimed to evaluate nutritional assessment by a network during first consultations in patients' homes. Patients identified by the regional ALS centre gave their informed consent. Assessment included functional, nutritional issues, evaluation of the need for help, whether personal or the use of aids, and noted any dietary supplementation and modification of the texture of food. Forty patients were seen a mean of 7.4 months after diagnosis; 52.5% had bulbar disease, 7.5% were malnourished; 29.4 +/- 10.1 kcal/kg/day were consumed and protein intake was 1.3 +/- 0.5 g/kg/day. Thirty-five percent of patients were anorexic, 43.8% reported taste disorders, and 70% had dysphagia, significantly associated with salivary stasis. Only 30% of dysphagic patients ate texture modified food, and 90% of patients with problems drinking liquids did not use a thickener. In conclusion, assessment at home by a nutritional network can be conducted promptly. Malnutrition is rare in early disease, despite the fact that patients' diets are often low in energy and dysphagia is common. Unexpected taste disorders are detected. Dysphagia is very common but inadequately addressed. Consequently, home assessment by the network led several beneficial interventions. PMID- 22775118 TI - The role of melanin-concentrating hormone in conditioned reward learning. AB - The orexigenic neuropeptide melanin-concentrating hormone (MCH) is well positioned to play a key role in connecting brain reward and homeostatic systems due to its synthesis in hypothalamic circuitry and receptor expression throughout the cortico-striatal reward circuit. Here we examined whether targeted-deletion of the MCH receptor (MCH-1R) in gene-targeted heterozygote and knockout mice (KO), or systemic treatment with pharmacological agents designed to antagonise MCH-1R in C57BL/6J mice would disrupt two putative consequences of reward learning that rely on different neural circuitries: conditioned reinforcement (CRf) and Pavlovian-instrumental transfer (PIT). Mice were trained to discriminate between presentations of a reward-paired cue (CS+) and an unpaired CS-. Following normal acquisition of the Pavlovian discrimination in all mice, we assessed the capacity for the CS+ to act as a reinforcer for new nose-poke learning (CRf). Pharmacological disruption in control mice and genetic deletion in KO mice impaired CRf test performance, suggesting MCH-1R is necessary for initiating and maintaining behaviors that are under the control of conditioned reinforcers. To examine a dissociable form of reward learning (PIT), a naive group of mice were trained in separate Pavlovian and instrumental lever training sessions followed by the PIT test. For all mice the CS+ was capable of augmenting ongoing lever responding relative to CS- periods. These results suggest a role for MCH in guiding behavior based on the conditioned reinforcing value of a cue, but not on its incentive motivational value. PMID- 22775119 TI - Immunomodulating and anti-infective effects of a novel strain of Lactobacillus paracasei that strongly induces interleukin-12. AB - Several studies have demonstrated that some strains of lactic acid bacteria (LAB) can elicit natural killer (NK) cell activities via interleukin-12 (IL-12) induction and protect against influenza virus (IFV) infection. LAB strains that strongly induce IL-12 are expected to be effective in protecting against IFV infection. In this study, we screened 85 strains for their ability to induce the in vitro production of IL-12, and Lactobacillus paracasei MoLac-1 most strongly induced IL-12. To examine the immunomodulating effects of MoLac-1, we have performed in vitro studies using murine splenocytes. Heat-killed MoLac-1 cells induced IL-12 and interferon-gamma (IFN-gamma) production by murine splenocytes. Experiments using splenocytes depleted of various cell populations indicated that macrophages might be a major source of MoLac-1-induced IL-12 secretion. Intracellular staining of IFN-gamma suggested that MoLac-1 activated NK cells and induced IFN-gamma production by NK cells in vitro. Oral administration of heat killed MoLac-1 increased the proportion of NK cells in spleen, and ameliorated the symptoms of IFV infection in mice. These results suggest that heat-killed MoLac-1 has the potential to modulate innate immunity and is useful for alleviation of the symptoms of IFV infection. PMID- 22775121 TI - Quasi-classical theory of electronic flux density in electronically adiabatic molecular processes. AB - The standard Born-Oppenheimer (BO) description of electronically adiabatic molecular processes predicts a vanishing electronic flux density (EFD). A previously proposed "coupled-channels" theory permits the extraction of the EFD from the BO wave function for one-electron diatomic systems, but attempts at generalization to many-electron polyatomic systems are frustrated by technical barriers. An alternative "quasi-classical" approach, which eliminates the explicit quantum dynamics of the electrons within a classical framework, yet retains the quantum character of the nuclear motion, appears capable of yielding EFDs for arbitrarily complex systems. Quasi-classical formulas for the EFD in simple systems agree with corresponding coupled-channels formulas. Results of the application of the new quasi-classical formula for the EFD to a model triatomic system indicate the potential of the quasi-classical scheme to elucidate the dynamical role of electrons in electronically adiabatic processes in more complex multiparticle systems. PMID- 22775120 TI - Generalized spinous follicular lichen nitidus with perifollicular granulomas. AB - The first report of spinous follicular lichen nitidus with perifollicular granulomas was by Madhok and Winkelmann in 1988. Since this report, a few cases of follicular or periappendageal lichen nitidus have been described, in a more localized form or without perifollicular granulomas. We describe a 5-year-old girl with the rare generalized spinous follicular variant of lichen nitidus with perifollicular granulomas. PMID- 22775122 TI - Posttraumatic stress disorder, depression, executive functioning, and autobiographical remembering in individuals with HIV and in carers of those with HIV in Iran. AB - Two studies examined autobiographical remembering in those with HIV (Study 1) and in carers of those with HIV (Study 2) in Iran. Study 1 investigated posttraumatic stress disorder (PTSD) and depression symptoms, executive control, and autobiographical remembering in those with HIV. Individuals with HIV (n = 34) and healthy controls (n = 34) completed the Impact of Event Scale-Revised, Beck's Depression Inventory-II, Beck's Anxiety Inventory, Autobiographical Memory Interview, Autobiographical Memory Test, Wisconsin Card Sorting Test, and Tower of London. The results indicated higher PTSD and depression symptoms among the HIV group. The findings also showed that those with HIV had lower levels of executive functioning, deficits in autobiographical remembering (semantic and episodic) and retrieved less specific autobiographical memories than the control group. Study 2 examined depression, executive functioning, and autobiographical memory performance among carers of those with HIV (n = 26) and healthy controls (n = 26). The same measures were completed as in Study 1. The results indicated higher depression among the carers group but the groups did not differ in terms of executive functioning or semantic recollection. The carers had lower episodic recall scores and less specific memories than the control group. The findings are discussed in terms of the processes involved in nonspecific retrieval of autobiographical material in relation to HIV. PMID- 22775123 TI - Reduced risk-taking behavior as a trait feature of anxiety. AB - Affect can have a significant influence on decision-making processes and subsequent choice. One particularly relevant type of negative affect is anxiety, which serves to enhance responses to threatening stimuli or situations. In its exaggerated form, it can lead to psychiatric disorders, with detrimental consequences for quality of life, including the ability to make choices. This study investigated, for the first time, how pathological anxiety affects risk taking behavior. In this study, 20 anxious participants meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for either generalized anxiety disorder (n = 10) and for panic attack disorder (n = 10), as well as 20 matched nonanxious controls, performed a gambling task. To investigate the tendency toward either a risk-seeking or a risk-averse behavior, we employed a task that did not allow for learning from outcomes. Anxious participants made significantly fewer risky choices than matched nonanxious participants. Specifically, they become risk-avoidant after gains. Moreover, anxious participants not only were less happy after gains but were also less sad after losses, and they also evinced less desire to change their choices after losses than did nonanxious participants. Importantly, whereas the desire to switch choice was followed by actual choice switch for all participants, happiness directly predicted subsequent risky choices, particularly in the nonanxious participants. Further analyses revealed that the anxious participants' risk avoidance behavior was independent of different types of anxiety disorder (panic attack disorder and generalized anxiety disorder) as well as of the effects of psychotropic drugs treatment. This study demonstrates a specific role for anxiety in individual decision making. In particular, hypersensitivity to potential threats and pessimistic evaluation of future events reduced risk-taking behavior. PMID- 22775124 TI - Experiential versus analytical emotion regulation and sleep: breaking the link between negative events and sleep disturbance. AB - Despite a long history of interest in emotion regulation as well as in the mechanisms that regulate sleep, the relationship between emotion regulation and sleep is not yet well understood. The present study investigated whether "an experiential approach"-defined by coping through affectively acknowledging, understanding, and expressing actual emotional experience and affective feeling about a situation-compared with a "cognitive analytical approach"-defined by the cognitive analysis of the causes, meanings and implications of the situation for the own self-would buffer the impact of an emotional failure experience on (1) emotional experience and (2) sleep structure assessed by EEG polysomnography. Twenty-eight healthy volunteers participated in this study. A direct comparison of the two emotion regulation strategies revealed that participants who were instructed to apply an experiential approach showed less fragmentation of sleep than participants who were instructed to apply an analytical approach. The use of an experiential approach resulted in a longer sleep time, higher sleep efficiency, fewer awakenings, less % time awake, and fewer minutes wake after sleep onset. Implications of the differential effects of these two forms of emotion regulation on sleep are discussed. PMID- 22775125 TI - Durable effects of cognitive restructuring on conditioned fear. AB - Studies of cognitive reappraisal have demonstrated that reinterpreting a stimulus can alter emotional responding, yet few studies have examined the durable effects associated with reinterpretation-based emotion regulation strategies. Evidence for the enduring effects of emotion regulation may be found in clinical studies that use cognitive restructuring (CR) techniques in cognitive-behavioral therapy (CBT) to alleviate anxiety. These techniques are based on cognitive theories of anxiety that suggest these disorders arise from biased cognitions; therefore, changing a person's thoughts will elicit durable changes in an individual's emotional responses. Despite the considerable success of CBT for anxiety disorders, durable effects associated with emotion regulation have not been thoroughly examined in the context of a laboratory paradigm. The goal of this study was to determine whether CR, a technique used in CBT and similar to cognitive reappraisal, could attenuate conditioned fear responses, and whether the effect would persist over time (24 hr). We conditioned participants using images of snakes or spiders that were occasionally paired with a mild shock to the wrist while we obtained subjective fear reports and electrodermal activity (EDA). After conditioning, half of the participants were randomly assigned to CR training aimed at decreasing their emotional response to the shock and the conditioned stimuli, while the other half received no such training. All participants returned 24 hr later to repeat the conditioning session. Compared with control participants, CR participants demonstrated a reduction in fear and EDA across sessions. These findings suggest that CR has durable effects on fear responding. PMID- 22775128 TI - Intergroup anxiety effects on implicit racial evaluation and stereotyping. AB - How does intergroup anxiety affect the activation of implicit racial evaluations and stereotypes? Given the common basis of social anxiety and implicit evaluative processes in memory systems linked to classical conditioning and affect, we predicted that intergroup anxiety would amplify implicit negative racial evaluations. Implicit stereotyping, which is associated primarily with semantic memory systems, was not expected to increase as a function of intergroup anxiety. This pattern was observed among White participants preparing to interact with Black partners, but not those preparing to interact with White partners. These findings shed new light on how anxiety, often elicited in real-life intergroup interactions, can affect the operation of implicit racial biases, suggesting that intergroup anxiety has more direct implications for affective and evaluative forms of implicit bias than for implicit stereotyping. These findings also support a memory-systems model of the interplay between emotion and cognition in the context of social behavior. PMID- 22775126 TI - Interpreting infant vocal distress: the ameliorative effect of musical training in depression. AB - An infant's cry is one of the most emotionally salient sounds in our environment. Depression is known to disrupt a mother's ability to respond to her infant, but it is not well-understood why such difficulties arise. One reason might be that depression disrupts the perceptual abilities necessary to interpret infant's affective cues. Given that musicians are known to have enhanced auditory perception, we assessed whether depression and previous musical training can impact on the ability to interpret distress in infant cries, as manipulated by changes in pitch. Depressed participants with musical training demonstrated better discriminative acuity of distress in infant cry bursts compared to those without. Non-depressed participants, with and without musical training, had levels comparable to musicians with depression. We suggest that previous musical training may act as a protective factor that maintains auditory perceptual abilities in the context of depression. These findings have potential implications for the development of novel training interventions to maintain sensitivity to infant vocal cues in individuals with postnatal depression. PMID- 22775127 TI - Correlates and characteristics of adolescents' encoded emotional arousal during family conflict. AB - Associations between adolescents' range of fundamental frequency, cortisol output, and self-reported emotional experience were examined during problem discussions with parents. Participants are a community-based sample of 56 boys and girls in a longitudinal study on conflict exposure. Results reveal that higher aggregate levels of range of fundamental frequency are associated with higher cortisol output and higher levels of self-reported negative emotions for boys and girls. Additionally, greater cortisol output is significantly associated with a slower time-to-peak of range of fundamental frequency for girls and with significantly less variability in range of fundamental frequency for boys. Implications of results for emotional development in adolescents, measurement, and modeling are discussed. PMID- 22775129 TI - Startle response and anxiety sensitivity: subcortical indices of physiologic arousal and fear responding. AB - There is a well-established and clinically meaningful relation between the cognitive-affective-based construct of anxiety sensitivity (AS) and risk for the development and maintenance of anxiety psychopathology (B. J. Cox, Fuentes, Borger, & Taylor, 2001). Research findings within this area have revealed mixed results; however, there is evidence to suggest that some individuals with anxiety disorder diagnoses may demonstrate enhanced subcortical arousal (e.g., exaggerated startle response to unexpected, aversive stimuli [A. M. Waters et al., 2008], and deficient prepulse inhibition [PPI; S. Ludewig, Ludewig, Geyer, Hell, & Vollenweider, 2002]), it is presently unclear whether these differences are found within the general population. To address this gap in the extant literature, the current investigation examined the impact of AS on acoustic startle response magnitude and PPI. Results indicated that individuals high and low in AS differ with regard to subcortical measures of arousal, with individuals expressing high levels of AS demonstrating enhanced startle response and deficient PPI. Results are discussed in terms of the role of the cognitive affective-based factor of AS in the context of physiologic markers for vulnerability for anxiety psychopathology. PMID- 22775130 TI - Rumination moderates the effects of daily events on negative mood: results from a diary study. AB - Rumination describes a detrimental response to distress that involves repetitive thoughts about one's emotional state and its causes and potential consequences. Many experimental studies have shown that induced state rumination exacerbates the effect of laboratory stressors on negative affect. The current study examines whether use of rumination in response to specific real-life events moderates the association between unpleasant daily events and negative mood. One hundred fifty seven undergraduate participants completed daily diaries for six consecutive days. The daily diaries assessed current mood, a survey of unpleasant daily events, and use of rumination in response to the most unpleasant daily event. Data were analyzed with a multilevel random coefficient modeling (MRCM) approach. It was predicted and found that use of rumination in daily life moderates the relation between unpleasant daily events and negative mood. On days when participants reported intense rumination use, higher levels of unpleasant daily events predicted higher levels of negative mood. By contrast, on days when participants reported lower use of rumination, higher levels of unpleasant events were not associated with higher levels of negative mood. This study is the first to demonstrate that real-life use of rumination moderates the relation between unpleasant events and mood in daily life. (PsycINFO Database Record (c) 2012 APA, all rights reserved). PMID- 22775131 TI - Not all collectivisms are equal: opposing preferences for ideal affect between East Asians and Mexicans. AB - Previous research has revealed differences in how people value and pursue positive affect in individualistic and collectivistic cultural contexts. Whereas Euro-Americans place greater value on high activation positive affect (HAP; e.g., excitement, enthusiasm, elation) than do Asian Americans and Hong Kong Chinese, the opposite is true for low activation positive affect (LAP; e.g., calmness, serenity, tranquility). Although the form of collectivism present in East Asia dictates that individuals control and subdue their emotional expressions so as to maintain harmonious relationships, the opposite norm emerges in Mexico and other Latin American countries, in that the cultural script of simpatia promotes harmony through the open and vibrant expression of positive emotion. Across two studies, we found that Mexicans display a pattern of HAP/LAP preference different from those from East Asian collectivistic cultures, endorsing HAP over LAP. PMID- 22775132 TI - Saccadic latency is modulated by emotional content of spatially filtered face stimuli. AB - Models of attention and emotion assign a special status to the processing of threat. While evidence for threat-related attentional bias in highly anxious individuals is robust, effects in the normal population are mixed. An important explanation for the absence of threat-related attentional bias in nonanxious individuals may relate to the spatial frequency components of stimuli. Here we report behavioral data from two experiments examining the relationship between spatial frequency components of emotional and neutral faces and fast saccadic orienting behavior. In Experiment 1 participants had to saccade toward a single face, filtered to include mostly low, high or broad spatial frequencies (LSF, HSF or BSF), posing a fearful, happy or neutral expression presented for 20 ms in the periphery. At BSF a general emotional effect was found whereby saccadic responses were faster for fearful and happy faces relative to neutral, with no significant differences between fearful and happy faces. At LSF both fearful and happy faces had shorter saccadic latencies in comparison to neutral, demonstrating an emotional bias consistent with the BSF data. However, at LSF fearful faces resulted in significantly faster saccades than happy faces indicating that this bias was stronger for threat-related faces. There was no difference in saccadic responses between any emotions at HSF. Experiment 2 showed that the emotional bias diminished for inverted stimuli suggesting that the results were not attributable to low-level image properties. The findings suggest an overall advantage in the oculomotor system for orientation to emotional stimuli and at LSF in particular, a significantly faster localization of threat conveyed by the face stimuli in all individuals. PMID- 22775133 TI - The emotional eyewitness: the effects of emotion on specific aspects of eyewitness recall and recognition performance. AB - The present set of experiments aimed to investigate the effects of negative emotion on specific aspects of eyewitness recall and recognition performance. The experience of emotion was manipulated between subjects, with participants either viewing a crime scenario (a mugging) or a neutral scenario (a conversation). Eyewitness recall was categorized into descriptions of the perpetrator, critical incident, victim, and environmental details. The completeness and accuracy of eyewitness recall across categories of detail were measured in Experiment 1. A significant main effect of negative emotion was found for the completeness of recall. Furthermore, a significant main effect of the completeness of eyewitness statements was found, but not for their accuracy. However, these main effects were qualified by a significant interaction between emotion and category of detail recalled. Specifically, emotional participants provided a more complete description of the perpetrator than neutral participants; however, they were less able than their neutral counterparts to describe what the perpetrator did to the victim. In light of these findings, Experiment 2 investigated whether enhanced completeness of perpetrator descriptions during recall translated into an enhanced ability to recognize the perpetrator from a photographic lineup by emotional compared with neutral participants. Results from Experiment 2 suggest that while emotional participants again provide a more complete description of the perpetrator, they are less able than their neutral counterparts to recognize the perpetrator from a photographic lineup. Results are discussed in terms of a retrieval motivation hypothesis of negative emotional experience and the possible consequences for eyewitness testimony. PMID- 22775134 TI - Higher sensitivity for low spatial frequency expressions in social anxiety: evident in indirect but not direct tasks? AB - We tested whether socially anxious individuals perform better in processing facial information with low spatial frequencies (LSFs). For this, we presented socially anxious and nonanxious participants with hybrid face stimuli that contained independent facial expressions in high (HSF) and LSF bands. In two tasks, participants either rated the images according to "angriness" or had to learn how hybrid facial expressions predicted the location of an upcoming target. We found mostly additive effects of LSF and HSF information in the rating task for both groups. In contrast, socially anxious participants showed better prediction performance for LSF expressions in the implicit learning task. We conclude that socially anxious participants are more sensitive to facial information within LSFs, but this higher sensitivity may become mostly evident in indirect tasks. PMID- 22775135 TI - Active control of approach-oriented posture is influenced by emotional reactions. AB - Emotions adaptively prepare the body to interact with the environment through execution of motor actions, but the extent to which emotional states modulate force control during directionally targeted movement tasks remains unknown. We sought to determine how emotions influence active control of approach-oriented posture. Participants (N = 43; 25 females) stood on a force plate and displaced their center of pressure (COP) anteriorly to a target at 50% of their maximum voluntary lean. After 7 s of real-time COP feedback, a picture representing 6 discrete categories (attack, mutilation, contamination, erotic couples, happy faces, and neutral objects) replaced the target and remained on the screen. Participants were instructed to maintain the target COP position throughout the trial. Deviation of the COP position relative to the target (root-mean-square error; RMSE) and error direction (constant error; CE) were evaluated during the feedback and picture portions of the trial. RMSE increased for all affective conditions following feedback occlusion. Following picture onset, lean error exhibited when viewing attack pictures was more anterior (i.e., greater CE) compared with the mutilation, contamination, and erotica conditions. Additionally, participants leaned more anteriorly (i.e., greater CE) during the happy faces condition compared with the mutilation and erotica conditions. Collectively, results indicate that the maintenance of an anterior COP position in the anterior direction is primarily modulated by the motivational direction of emotional stimuli. PMID- 22775136 TI - The regulatory benefits of high levels of affect perception accuracy: a process analysis of reactions to stressors in daily life. AB - Individuals attuned to affective signals from the environment may possess an advantage in the emotion-regulation realm. In two studies (total n = 151), individual differences in affective perception accuracy were assessed in an objective, performance-based manner. Subsequently, the same individuals completed daily diary protocols in which daily stressor levels were reported as well as problematic states shown to be stress-reactive in previous studies. In both studies, individual differences in affect perception accuracy interacted with daily stressor levels to predict the problematic outcomes. Daily stressors precipitated problematic reactions--whether depressive feelings (study 1) or somatic symptoms (study 2)--at low levels of affect perception accuracy, but did not do so at high levels of affect perception accuracy. The findings support a regulatory view of such perceptual abilities. Implications for understanding emotion regulation processes, emotional intelligence, and individual differences in reactivity are discussed. PMID- 22775137 TI - Effects of EMD in combination with bone swaging and calcium phosphate bone cement on periodontal regeneration in one-wall intrabony defects in dogs. AB - BACKGROUND AND OBJECTIVE: Although the application of EMD is a widely accepted periodontal-regenerative therapy, its effects on noncontained intrabony defects are unpredictable because of the lack of a space-making property. The combined use of EMD and autogenous bone grafts reportedly stimulates significant periodontal regeneration in intrabony defects. The aim of the present study was to evaluate the effects of EMD in combination with bone swaging (BS) and injectable calcium phosphate bone cement (CPC), which was placed into the spaces between the grafted swaged bone and the proximal host bone, on periodontal healing in one-wall intrabony defects in dogs. MATERIAL AND METHODS: One-wall intrabony defects (3 mm wide and 5 mm deep) were surgically created on the mesial and distal sides of the bilateral mandibular premolars in four dogs. The 16 defects were assigned to one of the following treatments: EMD only, BS only, EMD with BS (EMD + BS), or EMD with BS and CPC (EMD + BS + CPC). The animals were killed 8 wk after surgery for histologic evaluation. RESULTS: The height of newly formed bone was significantly greater in the EMD + BS + CPC group (3.73 +/- 0.30 mm) than in the BS-only (2.74 +/- 0.33 mm; p < 0.05) and EMD + BS (2.88 +/- 0.98 mm; p < 0.05) groups. The area of newly formed bone was significantly larger in the EMD + BS + CPC group (5.68 +/- 1.66 mm(2)) than in the EMD-only (3.68 +/- 0.33 mm(2); p < 0.05), BS-only (3.48 +/- 1.26 mm(2); p < 0.05) and EMD + BS (3.38 +/- 1.37 mm(2); p < 0.05) groups. The EMD-only (4.63 +/- 0.42 mm), EMD + BS (4.67 +/- 0.30 mm) and EMD + BS + CPC (4.78 +/- 0.54 mm) groups showed significantly greater cementum formation than did the BS-only group (3.93 +/- 0.56 mm; p < 0.05). CONCLUSION: These results indicate that treatment with EMD + BS + CPC promotes favorable periodontal healing in one-wall intrabony defects in dogs. PMID- 22775138 TI - Psychometric properties of the 'Spanish burnout inventory' among employees working with people with intellectual disability. AB - BACKGROUND: Burnout has been recognised as an important stress-related problem for employees working with people with intellectual disability. Researchers have been troubled by some of the psychometric limitations of the questionnaires developed to evaluate burnout. This study was designed to assess the psychometric properties of the Spanish Burnout Inventory. METHOD: The sample consisted of 697 Spanish employees working in intellectual disability services. The instrument is composed of 20 items distributed in four dimensions: Enthusiasm towards the job, Psychological exhaustion, Indolence and Guilt. The psychometric properties were examined through the following analyses: confirmatory factor analysis and reliability. To assess the factorial validity of the Spanish Burnout Inventory, four alternative models were tested. RESULTS: The four-factor model obtained an adequate data fit for the sample. The four sub-scales exhibited high reliability, with Cronbach alphas exceeding the critical value of 0.70. CONCLUSIONS: This study provides evidence showing the adequate psychometric properties of an alternative burnout measure that could facilitate the diagnosis of individuals with burnout. It recommends taking feelings of guilt into consideration in interventions designed to improve staff burnout. PMID- 22775140 TI - Binocular coordination in response to two-dimensional, three-dimensional and stereoscopic visual stimuli. AB - PURPOSE: We were particularly interested in whether binocular coordination when viewing stereoscopic images would be more comparable to when viewing a 2D representation, or when viewing a real stimulus array in depth. METHODS: Data are reported from an experiment examining binocular coordination in response to stereoscopically presented stimuli. Movements of both eyes were recorded as participants viewed LED stimuli in a real scene with depth, a 2D image of the scene, and a stereoscopic image of the scene. RESULTS: When viewing real LEDs, vergence during saccades re-aligned the eyes in depth where necessary, with smaller adjustments during the following fixation. In contrast, when viewing the stereoscopic representation, vergence during saccades did not re-align the eyes in depth. The only effect of target depth on vergence occurred during the following fixation. CONCLUSIONS: We conclude that disparity in parafoveal objects, in isolation from other depth cues (and, minimally, conflicting with blur), was insufficient for the visual system to target saccades appropriately in depth. PMID- 22775141 TI - Tracing and quantifying lake water and groundwater fluxes in the area under mining dewatering pressure using coupled O and H stable isotope approach. AB - Oxygen and hydrogen stable isotopic compositions of precipitation, lake water and groundwater were used to quantitatively asses the water budget related to water inflow and water loss in natural lakes, and mixing between lake water and aquifer groundwater in a mining area of the Lignite Mine Konin, central Poland. While the isotopic composition of precipitation showed large seasonal variations (delta(2)H from-140 to+13 0/00 and delta(18)O from-19.3 to+7.6 0/00), the lake waters were variously affected by evaporation (delta(2)H from-44 to-21 0/00 and delta(18)O from-5.2 to-1.7 0/00) and the groundwater showed varying contribution from mixing with surface water (delta(2)H from-75 to-39 0/00 and delta(18)O from-10.4 to-4.8 0/00). The lake water budget was estimated using a Craig-Gordon model and isotopic mass balance constraint, which enabled us to identify various water sources and to quantify inflow and outflow for each lake. Moreover, we documented that a variable recharge of lake water into the Tertiary aquifer was dependent on mining drainage intensity. A comparison of coupled delta(2)H-delta(18)O data with hydrogeological results indicated better precision of the delta(2)H-based calculations. PMID- 22775139 TI - Comparative proteomic profiling of dystroglycan-associated proteins in wild type, mdx, and Galgt2 transgenic mouse skeletal muscle. AB - Dystroglycan is a major cell surface glycoprotein receptor for the extracellular matrix in skeletal muscle. Defects in dystroglycan glycosylation cause muscular dystrophy and alterations in dystroglycan glycosylation can impact extracellular matrix binding. Here we describe an immunoprecipitation technique that allows isolation of beta dystroglycan with members of the dystrophin-associated protein complex (DAPC) from detergent-solubilized skeletal muscle. Immunoprecipitation, coupled with shotgun proteomics, has allowed us to identify new dystroglycan associated proteins and define changed associations that occur within the DAPC in dystrophic skeletal muscles. In addition, we describe changes that result from overexpression of Galgt2, a normally synaptic muscle glycosyltransferase that can modify alpha dystroglycan and inhibit the development of muscular dystrophy when it is overexpressed. These studies identify new dystroglycan-associated proteins that may participate in dystroglycan's roles, both positive and negative, in muscular dystrophy. PMID- 22775142 TI - The detection of periapical pathosis using digital periapical radiography and cone beam computed tomography - part 2: a 1-year post-treatment follow-up. AB - AIM: Part 2 of this clinical study aims to compare the radiographic change in periapical status of individual roots determined using digital periapical radiographs versus cone beam computed tomography (CBCT) 1year after primary root canal treatment and to determine the radiological outcome of treatment for each tooth. METHODOLOGY: Periapical radiographs and CBCT scans of 123 teeth in 99 patients assessed 1year after completion of primary root canal treatment by a single operator were compared with their respective pre-treatment (diagnostic) periapical radiographs and CBCT scans. The presence or absence as well as the increase or decrease in size of existing periapical radiolucency was assessed by a consensus panel consisting of two calibrated examiners. The panel viewed the images under standardized conditions. Paired comparison of the outcome diagnosis of individual roots and teeth was performed using generalized McNemar's or Stuart Maxwell test of symmetry analysis. RESULTS: The 'healed' rate (absence of periapical radiolucency) for all roots combined was 92.7% using periapical radiographs and 73.9% for CBCT (P<0.001). This rate increased to 97.2% and 89.4%, respectively, when the 'healing' group (reduced size of periapical radiolucency) was included (P<0.001). A statistically significant difference in outcome diagnosis of single roots was observed between DPA and CBCT in single-rooted teeth and the buccal or mesio-buccal roots of multi-rooted teeth (P<0.05). Analysis by tooth revealed that the 'healed' rate (absence of periapical radiolucency) was 87% using periapical radiographs and 62.5% using CBCT (P<0.001). This increased to 95.1% and 84.7%, respectively, when the 'healing' group (reduced size of periapical radiolucency) was included (P<0.002). Outcome diagnosis of teeth showed a statistically significant difference between systems (P<0.001). Reconstructed CBCT images revealed more failures (17.6%) in teeth with no pre-operative periapical radiolucencies compared with periapical radiographs (1.3%) (P=0.031). In teeth with existing pre-operative periapical radiolucencies, reconstructed CBCT images also showed more failures (13.9%) compared with periapical radiographs (10.4%). CONCLUSION: Diagnosis using CBCT revealed a lower healed and healing rate for primary root canal treatment than periapical radiographs, particularly in roots of molars. There was a 14 times increase in failure rate when teeth with no pre-operative periapical radiolucencies were assessed with CBCT compared with periapical radiographs at 1year. PMID- 22775143 TI - Embedded surface relief gratings by a simple method to improve absorption and electrical properties of polymer solar cells. AB - We demonstrate a simple rubbing hole injection layer (HIL) to form surface relief gratings (SRGs) on the functional layers of polymer solar cells (PSCs). PSCs studied in this work consist of an ITO/PEDOT:PSS(HIL)/P3HT:PCBM(photoactive layer)/LiF/Al structure. SRGs are successfully formed on HIL in an effective rubbing process, and are over printed on the photoactive layer and cathode consequently. These triplet SRGs change the morphologies of interfaces of PSCs, which can increase optical path lengths, interaction between HIL and P3HT chains, and interface areas between electrode and photoactive layer. Both light trapping and electrical improvement are confirmed by theory and experiments, which lead to overall increase in short-circuit current density, fill factor, and power conversion efficiency (PCE) of PSCs. An average PCE of 3.8% is achieved from PSCs with SRGs without thermal annealing. Different from the directly rubbing the donor polymer film, a suitable degree of orientation of P3HT presents a lower dichroic ratio and higher photovoltaic response in our work. PMID- 22775145 TI - Effect of UV and UV/H2O2 in the presence of chloramines on NDMA formation potential of tramadol. AB - This study evaluates the effect of UV-C and UV-C/H(2)O(2) in the presence of chloramines on the N-nitrosodimethylamine formation potential (NDMA FP) of tramadol as a model precursor. The experiments were performed at high initial concentrations of TMDL (i.e., 20 mg/L) in order to elucidate the structures of TMDL byproducts. Twenty-four byproducts were identified in UV-C, UV C/monochloramine, and UV/H(2)O(2)/monochloramine oxidation of tramadol using MS(3) capabilities of a hybrid quadrupole-linear ion trap mass spectrometer, combined with online hydrogen/deuterium (H/D) exchange experiments. Oxidative cleavage of methoxy and methoxybenzene moiety, O-demethylation, hydroxylation, and cyclohexane ring-opening were identified as major reaction mechanisms of tramadol in UV oxidation. Addition of monochloramine decreased the degradation rates of tramadol and its byproducts and yielded several monochlorinated derivatives. The oxidation rates were significantly enhanced in the presence of H(2)O(2), and byproducts of oxidative benzene ring-opening were detected. The majority of the identified byproducts are likely to have a higher NDMA FP than the parent compound due to a reduced steric hindrance and/or insertion of electron-donating hydroxyl groups in the N,N-dimethylamine side chain. This was confirmed by the results of NDMA FP tests, which showed that the formation of NDMA was enhanced up to four times depending on the process conditions in UV alone and in UV and UV/H(2)O(2) in the presence of monochloramine. Prolonged oxidation by hydroxyl radicals in UV/H(2)O(2)/monochloramine process mineralized some of the byproducts and slightly reduced the NDMA FP at the end of the treatment. The obtained degradation pathway of tramadol allowed the correlation of changes in NDMA FP during oxidation with its major oxidative transformation reactions. This manuscript demonstrates the significance of oxidation byproducts as NDMA precursors and emphasizes the need for their consideration when evaluating the evolution of NDMA FP during oxidative treatment. PMID- 22775144 TI - In vitro suppression of growth of murine WEHI-3 leukemia cells and in vivo promotion of phagocytosis in a leukemia mice model by indole-3-carbinol. AB - Indole-3-carbinol (I3C), a potential anticancer substance, can be found in cruciferous (cabbage family) vegetables, mainly cauliflower and Chinese cabbage. However, the bioactivity of I3C on the apoptotic effects of murine leukemia WEHI 3 cells and promotion of immune responses in leukemia mice model are unclear. In this study, we investigated the effect of I3C on cell-cycle arrest and apoptosis in vitro and immunomodulation in vivo. I3C decreased the viable WEHI-3 cells and caused morphological changes in a concentration- and time-dependent manner. I3C also led to G0/G1 phase arrest, decreased the levels of cyclin A, cyclin D, and CDK2, and increased the level of p21(WAF1/CIP1). Flow cytometric analyses further proved that I3C promoted ROS and intracellular Ca(2+) production and decreased the levels of DeltaPsi(m) in WEHI-3 cells. Cells after exposure to I3C for 24 h showed DNA fragmentation and chromatin condensation. Comet assay also indicated that I3C induced DNA damage in examined cells. I3C increased the levels of cytochrome c, FADD, GADD153, GRP78, and caspase-12 as well as induced activities of caspase-3, -8, and -9. Moreover, I3C attenuated NF-kappaB DNA binding activity in I3C-treated WEHI-3 cells as shown by EMSA and Western blotting analyses. In the in vivo study, we examined the effects of I3C on WEHI-3 leukemia mice. Results showed that I3C increased the level of T cells and decreased the level of macrophages. I3C also reduced the weights of liver and spleen, and it promoted phagocytosis by macrophages as compared to the nontreated leukemia mice group. On the basis of our results, I3C affects murine leukemia WEHI-3 cells both in vitro and in vivo. PMID- 22775146 TI - Insight into mammalian mitochondrial DNA segregation. AB - Mitochondrial DNA (mtDNA) is essential for aerobic energy production in eukaryotic cells, and mutations in this genome can lead to mitochondrial dysfunction. Human mtDNA mutations are typically heteroplasmic, a mix of mutant and wild-type genomes, which can present as a heterogeneous group of disorders ranging in severity from mild to fatal, and commonly affecting highly aerobic tissues such as heart, skeletal muscle, and neurons. During the 1990s, many research groups started to notice that mtDNA mutations could segregate depending upon the mutation and tissue. This segregation pattern can have a direct effect on the onset and severity of these mutations. However, these segregation patterns could not be easily explained by respiratory chain function, implying that there is regulation of mtDNA independent of its bioenergetic role. A lot of research on this topic has been largely descriptive, but over the last several years advances in mitochondrial biology have provided some mechanistic insight into the regulation of the organelle and its genome. This review addresses these advances with respect to somatic segregation of mtDNA in mammals. PMID- 22775147 TI - Increased frequencies of Th17 and Th22 cells in the peripheral blood of patients with secondary syphilis. AB - T-helper (Th) 17 and the more recently identified Th22 cells are of great importance in host defense against pathogens, but can also be responsible for chronic inflammatory disorders. However, the roles of the two cell subsets in syphilis remain elusive. In this study, we show that the frequencies of Th17 and Th22 cells are significantly increased in the peripheral blood of patients with secondary syphilis (SS). A significant positive correlation is observed between Th17 and Th22 cells, whereas a negative correlation exists between Th17 and Th1 cells. Moreover, the frequency of Th17 cells has a significant positive correlation with the plasma interleukin 6 (IL-6) or IL-1beta levels, and the frequency of Th22 cells is positively correlated with the IL-6 or IL-23 levels. Finally, the elevated frequencies of Th17 and Th22 cells are positively associated with plasma C-reactive protein levels. Our results suggest that Th17 and Th22 cells may be implicated in the pathogenesis of the SS. PMID- 22775149 TI - Intersublevel spectroscopy on single InAs-quantum dots by terahertz near-field microscopy. AB - Using scattering-type near-field infrared microscopy in combination with a free electron laser, intersublevel transitions in buried single InAs quantum dots are investigated. The experiments are performed at room temperature on doped self assembled quantum dots capped with a 70 nm GaAs layer. Clear near-field contrast of single dots is observed when the photon energy of the incident beam matches intersublevel transition energies, namely the p-d and s-d transition of conduction band electrons confined in the dots. The observed room-temperature line width of 5-8 meV of these resonances in the mid-infrared range is significantly below the inhomogeneously broadened spectral lines of quantum dot ensembles. The experiment highlights the strength of near-field microspectroscopy by demonstrating signals from bound-to-bound transitions of single electrons in a probe volume of the order of (100 nm)(3). PMID- 22775148 TI - Human breath gas analysis in the screening of gestational diabetes mellitus. AB - BACKGROUND: We present a pilot study on the feasibility of the application and advantages of online, noninvasive breath gas analysis (BGA) by proton transfer reaction quadrupole mass spectrometry for the screening of gestational diabetes mellitus (GDM) in 52 pregnant women by means of an oral glucose tolerance test (OGTT). SUBJECTS AND METHODS: We collected and identified samples of end-tidal breath gas from patients during OGTT. Time evolution parameters of challenge responsive volatile organic compounds (VOCs) in human breath gas were estimated. Multivariate analysis of variance and permutation analysis were used to assess feasibility of BGA as a diagnostic tool for GDM. RESULTS: Standard OGTT diagnosis identified pregnant women as having GDM (n = 8), impaired glucose tolerance (n = 12), and normal glucose tolerance (n = 32); a part of this latter group was further subdivided into a "marginal" group (n = 9) because of a marginal high 1-h or 2-h OGTT value. We observed that OGTT diagnosis (four metabolic groups) could be mapped into breath gas data. The time evolution of oxidation products of glucose and lipids, acetone metabolites, and thiols in breath gas after a glucose challenge was correlated with GDM diagnosis (P = 0.035). Furthermore, basal (fasting) values of dimethyl sulfide and values of methanol in breath gas were inversely correlated with phenotype characteristics such as homeostasis model assessment of insulin resistance index (R = -0.538; P = 0.0002, P(corrected) = 0.0034) and pregestational body mass index (R = -0.433; P = 0.0013, P(corrected) = 0.022). CONCLUSIONS: Noninvasive BGA in challenge response studies was successfully applied to GDM diagnosis and offered an insight into metabolic pathways involved. We propose a new approach to the identification of diagnosis thresholds for GDM screening. PMID- 22775150 TI - Identification of SRC as a potent drug target for asthma, using an integrative approach of protein interactome analysis and in silico drug discovery. AB - Network-biology inspired modeling of interactome data and computational chemistry have the potential to revolutionize drug discovery by complementing conventional methods. We consider asthma, a complex disease characterized by intricate molecular mechanisms, for our study. We aim to integrate prediction of potent drug targets using graph-theoretical methods and subsequent identification of small molecules capable of modulating activity of the best target. In this work, we construct the protein interactome underlying this disease: Asthma Protein Interactome (API). Using a strategy based on network analysis of the interactome, we identify a set of potential drug targets for asthma. Topologically and dynamically, v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC) emerges as the most central target in API. SRC is known to play an important role in promoting airway smooth muscle cell growth and facilitating migration in airway remodeling. From interactome analysis, and with the reported role in respiratory mechanisms, SRC emerges as a promising drug target for asthma. Further, we proceed to identify leads for SRC from a public database of small molecules. We predict two potential leads for SRC using ligand-based virtual screening methodology. PMID- 22775151 TI - Safety and tolerability of a body wash and moisturizer when applied to infants and toddlers with a history of atopic dermatitis: results from an open-label study. AB - Improving skin barrier function and moisturizing without irritation are important components of managing patients with atopic dermatitis. This study evaluated the safety and tolerability of a body wash and moisturizer regimen for infants and toddlers with atopic dermatitis. This was an open-label study involving 56 children (3-36 months old) with a history of atopic dermatitis. The skin care regimen (Cetaphil Restoraderm Skin Restoring Body Wash and Cetaphil Restoraderm Skin Restoring Moisturizer; Galderma Laboratories, L.P.) was used at least once daily, but no more than twice daily, for 4 weeks. The primary variable of interest was the worst postbaseline scores for local tolerability (expressed as success or failure) using a 4-point scale for each component (erythema, edema, scaling and dryness, rash, and signs of discomfort upon application). Assessments of moisture content of the stratum corneum and transepidermal water loss were also performed. Fifty-three children completed the study. The percentage of subjects with no erythema increased from 33.9% to 50.0% by Week 4. The percentage of subjects with no scaling or dryness increased from 58.9% to 85.2% at Week 4. A statistically significant increase in corneometry from baseline (p < 0.001) and a statistically significant decrease in transepidermal water loss (p = .009) were observed. The body wash and moisturizer regimen was safe and well tolerated and improved hydration and skin barrier function in infants and toddlers as young as 3 months of age with a history of atopic dermatitis. PMID- 22775152 TI - Tropicamide 1% mydriatic effect: comparison between spray in closed eyes and eye drops in open eyes. AB - PURPOSE: The aim of this study was to evaluate by serial measurements, pupil mydriasis produced by topical application of tropicamide 1% using a spray in a closed eye or instillation in an open eye in adult and elderly populations. METHODS: The research was done from February to April of 2011 in the Policlinica Ronaldo Gazolla, located in the Arcos da Lapa Campus of Estacio de Sa University, RJ- Brazil. It was a clinical trial, controlled and randomized, made in a series of 50 patients that were being prepared for ophthalmoscopy examination. They were submitted to eye drop administration of 1% tropicamide in an open eye and to eyelid margin vaporization in a closed eye. The eyes were chosen for the administration of drops or spray according to a pseudo-random numbers table from Excel (2007) before application. The pupil diameter was measured before instillation and after 10, 20, and 30 min in both eyes, with a millimeter ruler. Biostat 5.0 software was used for statistical calculations. RESULTS: Tropicamide 1% was vaporized in a group that presented the following average pupil diameters: 3 mm before the application; 4.16 mm in 10 min; 5 mm in 20 min; and 5.35 mm in 30 min. The group in which tropicamide 1% was instilled presented 2.96 mm of average pupil diameter before the application; 4.22 mm at 10 min; 5.02 mm at 20 min; and 5.44 at 30 min. The two way analysis of variance showed P<0.0001, and the Tukey test performed for comparisons among the groups showed statistical significant differences among all groups except when the measurements were done at the same time. CONCLUSION: The vaporized tropicamide 1% mydriatic effect in closed eyes was clinically equivalent to the instillation effect of eye drop in open eyes. Other mydriatic drugs sprayed in closed eyes may not have the same effect. PMID- 22775197 TI - Reduced and exact quantum dynamics of the vibrational relaxation of a molecular system interacting with a finite-dimensional bath. AB - We investigate the vibrational relaxation of a Morse oscillator, nonlinearly coupled to a finite-dimensional bath of harmonic oscillators at zero temperature, using two different approaches: Reduced dynamics with the help of the Lindblad formalism of reduced density matrix theory in combination with Fermi's Golden Rule, and exact dynamics (within the chosen model) with the multiconfiguration time-dependent Hartree (MCTDH) method. Two different models have been constructed, the situation where the bath spectrum is exactly resonant with the anharmonic oscillator transition frequencies, and the case for which the subsystem is slightly off-resonant with the environment. At short times, reduced dynamics calculations describe the relaxation process qualitatively well but fail to reproduce recurrences observed with MCTDH for longer times. Lifetimes of all the vibrational levels of the Morse oscillator have been calculated, and both Lindblad and MCTDH results show the same dependence of the lifetimes on the initial vibrational state quantum number. A prediction, which should be generic for adsorbate systems is a striking, sharp increase of lifetimes of the subsystem vibrational levels close to the dissociation limit. This is contradictory with harmonic/linear extrapolation laws, which predict a monotonic decrease of the lifetime with initial vibrational quantum number. PMID- 22775198 TI - Sibling differences in parent-child conflict and risky behavior: a three-wave longitudinal study. AB - To better understand why siblings growing up in the same family are often as different as unrelated individuals, this study explored the role of differential experiences with parents in the development of sibling differences. Cross-lagged models tested directions of effect by examining whether differential parent-child conflict predicted sibling differences in risky behavior over time, or vice versa. Participants were mothers, fathers, and the 2 eldest adolescent siblings (mean ages at Time 1 = 15.12 and 12.58 years) from 355 European American, working and middle-class families. On 3 occasions over a 2-year period, mothers and fathers reported on their conflict with each of the 2 siblings, and siblings reported on their own risky behavior. Results revealed that, controlling for sibling age differences and average levels of conflict and risky behavior at Time 1, youths who had more conflict with their mothers and fathers in relation to their siblings subsequently engaged in relatively more risky behavior. Also, youths who engaged in more risky behavior in relation to their siblings experienced relatively more conflict with their fathers, but not mothers, at later time points. Findings highlight the importance of examining both family dynamics and child characteristics in understanding sibling differentiation, and illuminate potential differences in parenting processes involving mothers versus fathers. PMID- 22775199 TI - Insulin at normal physiological levels does not prolong QT(c) interval in thorough QT studies performed in healthy volunteers. AB - AIMS: Food is known to shorten the QT(c) (QT(c)I and QT(c)F) interval and has been proposed as a non-pharmacological method of confirming assay sensitivity in thorough QT (TQT) studies and early phase studies in medicines research. Intake of food leads to a rise in insulin levels together with the release of C-peptide in equimolar amounts. However, it has been reported that euglycaemic hyperinsulinemia can prolong the QT(c) interval, whilst C-peptide has been reported to shorten the QT(c) interval. Currently there is limited information on the effects of insulin and C-peptide on the electrocardiogram (ECG). This study was performed to assess the effect of insulin, glucose and C-peptide on the QT(c) interval under the rigorous conditions of a TQT study. METHODS: Thirty-two healthy male and female, Caucasian and Japanese subjects were randomized to receive six treatments: (1) placebo, (2) insulin euglycaemic clamp, (3) carbohydrate rich 'continental' breakfast, (4) calorie reduced 'American' FDA breakfast, (5) moxifloxacin without food, and (6) moxifloxacin with food. Measurements of ECG intervals were performed automatically with subsequent adjudication in accordance with the ICH E14 guideline and relevant amendments. RESULTS: No effect was observed on QT(c)F during the insulin euglycaemic clamp period (maximal shortening of QT(c) F by 2.6 ms, not significant). Following ingestion of a carbohydrate rich 'continental' breakfast or a calorie reduced 'American' FDA standard breakfast, a rapid increase in insulin and C-peptide concentrations were observed. Insulin concentrations showed a peak response after the 'continental' breakfast observed at the first measurement time point (0.25 h) followed by a rapid decline. Insulin concentrations observed with the 'American' breakfast were approximately half of those seen with the 'continental' breakfast and showed a similar pattern. C-peptide concentrations showed a peak response at the first measurement time point (0.25 h) with a steady return to baseline at the 6 h time point. The response to the 'continental' breakfast was approximately double that of the 'American' FDA breakfast. A rapid onset of the effect on QT(c) F was observed with the 'continental' breakfast with shortening by >5 ms in the time interval from 1 to 4 h. After the 'American' FDA breakfast, a similar but smaller effect was seen. CONCLUSIONS: The findings of this study demonstrate that there was no change in QT(c) during the euglycaemic clamp. Given that insulin was raised to physiological concentrations comparable with those seen after a meal, whilst the release of C-peptide was suppressed, insulin appears to have no effect on the QT(c) interval in either direction. The results suggest a relationship exists between the shortening of QT(c) and C-peptide concentrations and indicate that glucose may have a QT(c) prolonging effect, which will require further research. PMID- 22775200 TI - Pseudoknot preorganization of the preQ1 class I riboswitch. AB - To explore folding and ligand recognition of metabolite-responsive RNAs is of major importance to comprehend gene regulation by riboswitches. Here, we demonstrate, using NMR spectroscopy, that the free aptamer of a preQ(1) class I riboswitch preorganizes into a pseudoknot fold in a temperature- and Mg(2+) dependent manner. The preformed pseudoknot represents a structure that is close to the ligand-bound state and that likely represents the conformation selected by the ligand. Importantly, a defined base pair mutation within the pseudoknot interaction stipulates whether, in the absence of ligand, dimer formation of the aptamer competes with intramolecular pseudoknot formation. This study pinpoints how RNA preorganization is a crucial determinant for the adaptive recognition process of RNA and ligand. PMID- 22775201 TI - Relaxation practice and physiologic regulation in a national sample of older Taiwanese. AB - OBJECTIVES: To compare the effects of relaxation practice and other exercise on a multisystem measure of physiologic dysregulation in a national sample of older Taiwanese. DESIGN: The study was a cross-sectional survey. SETTINGS/LOCATION: The study was conducted in Taiwan. SUBJECTS: A population-based sample of 1036 adults aged 53 and older completed an in-home interview and in-hospital physical examination. The final model is based on 934 respondents with complete data. OUTCOME MEASURES: The outcome measures were overall dysregulation, based on 26 biomarkers, and subscores for cardiovascular/metabolic risk factors and inflammatory markers. RESULTS: After adjustment for age and sex, overall dysregulation is 0.35 of a standard deviation (SD) lower for practitioners of relaxation techniques compared with nonpractitioners. The effect of exercise is smaller: 0.19 SD difference between those who exercise regularly and those who do not exercise. Similar effects of relaxation practice and regular exercise were found on inflammation, but smaller effects for cardiovascular/metabolic risk factors. In the presence of controls for sociodemographic characteristics, medication use, and a wide range of self-reported and interviewer-assessed health indicators, the effect of relaxation practice is attenuated but remains sizable ( 0.19 of a SD for overall dysregulation); regular exercise has a comparable effect (-0.16 of a SD). The effects are similar for the inflammation subscore, but not significant for cardiovascular/metabolic risk factors after adjusting for health status. CONCLUSIONS: The physiologic benefits of relaxation practice that have been demonstrated in small experimental studies are also evident in the general population of older Taiwanese who practice these techniques in everyday life. Relaxation practice is associated with lower levels of physiologic dysregulation, particularly with respect to inflammation. Among this sample of older adults, the effect appears to be at least as large as that for exercise. Older people with limited ability to engage in vigorous exercise may especially welcome such information. PMID- 22775202 TI - Measurement of air and VOC vapor fluxes during gas-driven soil remediation: bench scale experiments. AB - In this laboratory study, an experimental method was developed for the quantitative analyses of gas fluxes in soil during advective air flow. One dimensional column and two- and three-dimensional flow chamber models were used in this study. For the air flux measurement, n-octane vapor was used as a tracer, and it was introduced in the air flow entering the physical models. The tracer (n octane) in the gas effluent from the models was captured for a finite period of time using a pack of activated carbon, which then was analyzed for the mass of n octane. The air flux was calculated based on the mass of n-octane captured by the activated carbon and the inflow concentration. The measured air fluxes are in good agreement with the actual values for one- and two-dimensional model experiments. Using both the two- and three-dimensional models, the distribution of the air flux at the soil surface was measured. The distribution of the air flux was found to be affected by the depth of the saturated zone. The flux and flux distribution of a volatile contaminant (perchloroethene) was also measured by using the two-dimensional model. Quantitative information of both air and contaminant flux may be very beneficial for analyzing the performance of gas driven subsurface remediation processes including soil vapor extraction and air sparging. PMID- 22775203 TI - Conyzagenin-A and B, two new epimeric lanostane triterpenoids from Conyza canadensis. AB - Two new epimeric lanostane triterpenoids Conyzagenin-A and Conyzagenin-B were isolated from roots of Conyza canadensis, along with nine known compounds. The structures of these triterpenoids were elucidated by detailed spectral methods and chemical derivatisation. PMID- 22775204 TI - Changes in hope and health-related quality of life in couples following acute myocardial infarction: a quantitative longitudinal study. AB - BACKGROUND: Acute myocardial infarction (AMI) is a life-changing event that affects both the patient and the family and can have an influence on hope as well as HRQoL during the recovery period. AIMS: To compare self-rated scores of hope and health-related quality of life (HRQoL) 1, 7, 13 and 25 months, after an AMI with regard to (i) differences across time, and (ii) differences between patients and their partners. DESIGN: Explorative and longitudinal study. METHODS: In this nonrandomized study, Short Form 36 Health Questionnaire (SF-36) and Herth Hope Index-Swedish (HHI-S) questionnaires were completed by thirteen post-AMI patients and their partners. Data were collected on four occasions. RESULTS: In general, hope as well as HRQoL scores increased over time. A 2 (groups) * 4 (times) anova for mixed design showed significant changes in mental as well as in physical health over time but no significant effect of group on mental or physical health. Calculation of the minimum detectable change (MDC-index) for HHI-S and SF-36 revealed that scores between data collection points were not stable. conclusion: Our results show that although hope and HRQoL scores increased, only a few of the changes were statistically significant. Neither HHI-S nor SF-36 seems to measure stable states. Changes in hope and HRQoL levels may be due to participants striving to adapt to the current situation. RELEVANCE TO CLINICAL PRACTICE: These results can be used in the training of nursing staff to enhance their understanding of the significance of a family-centred approach after an AMI. PMID- 22775205 TI - The firing patterns of spinal neurons: in situ patch-clamp recordings reveal a key role for potassium currents. AB - Neuron firing patterns underpin the detection and processing of stimuli, influence synaptic interactions, and contribute to the function of networks. To understand how intrinsic membrane properties determine firing patterns, we investigated the biophysical basis of single and repetitive firing in spinal neurons of hatchling Xenopus laevis tadpoles, a well-understood vertebrate model; experiments were conducted in situ. Primary sensory Rohon-Beard (RB) neurons fire singly in response to depolarising current, and dorsolateral (DL) interneurons fire repetitively. RB neurons exhibited a large tetrodotoxin-sensitive sodium current; in DL neurons, the sodium current density was significantly lower. High voltage-activated calcium currents were similar in both neuron types. There was no evidence of persistent sodium currents, low-voltage-activated calcium currents, or hyperpolarisation-activated currents. In RB neurons, the potassium current was dominated by a tetraethylammonium-sensitive slow component (I(Ks) ); a fast component (I(Kf) ), sensitive to 4-aminopyridine, predominated in DL neurons. Sequential current-clamp and voltage-clamp recordings in individual neurons suggest that high densities of I(Ks) prevent repetitive firing; where I(Ks) is small, I(Kf) density determines the frequency of repetitive firing. Intermediate densities of I(Ks) and I(Kf) allow neurons to fire a few additional spikes on strong depolarisation; this property typifies a novel subset of RB neurons, and may activate escape responses. We discuss how this ensemble of currents and firing patterns underpins the operation of the Xenopus locomotor network, and suggest how simple mechanisms might underlie the similar firing patterns seen in the neurons of diverse species. PMID- 22775206 TI - Synthesis and photocatalytic activity of titania monoliths prepared with controlled macro- and mesopore structure. AB - Herein, we report a one-pot synthesis of crack-free titania monoliths with hierarchical macro-mesoporosity and crystalline anatase walls. Bimodal macroporosity is created through the polymer-induced phase separation of poly(furfuryl alcohol). The cationic polymerization of furfuryl alcohol is performed in situ and subsequently the polymer becomes immiscible with the aqueous phase, which includes titanic acid. Addition of template, Pluronic F127, increases the mesopore volume and diameter of the resulting titania, as the poly(ethylene glycol) block interacts with the titania precursor, leading to assisted assembly of the metal oxide framework. The hydrophobic poly(propylene glycol) micelle core could itself be swollen with monomeric and oligomeric furfuryl alcohol, allowing for mesopores as large as 18 nm. Variations in synthesis parameters affect porosity; for instance furfuryl alcohol content changes the size and texture of the macropores, water content changes the grain size of the titania and Pluronic F127 content changes the size and volume of the mesopore. Morphological manipulation improves the photocatalytic degradation of methylene blue. Light can penetrate several millimeters into the porous monolith, giving these materials possible application in commercial devices. PMID- 22775207 TI - Serine-proteases as plasminogen activators in terms of fibrinolysis. AB - OBJECTIVES: This review should give an overview about the natural human plasminogen activators and their various modified variants as well as similar substances isolated from animals, microorganisms and plants. When a blood clot is formed in a blood vessel, it avoids the oxygen supply of the surrounding tissue. A fast fibrinolytic therapy should redissolve the blood vessel and reduce the degradation of the tissue. All proteases that are part of the human blood coagulation and fibrinolytic system belong to the serine protease family. t-PA (tissue plasminogen activator) and u-PA (urokinase plasminogen activator) are the naturally occurring fibrinolytic agents that are also used in therapy. KEY FINDINGS: Despite many years of research, t-PA is still the gold standard in fibrinolytic therapy. But it has to be given as an infusion, which needs time. Modified fibrinolytic substances are, were, or perhaps will be in the market. They have different advantages over t-PA, but often the disadvantages predominate. CONCLUSION: Many substances have been developed but an optimal fibrinolytic agent combined with a simple administration is not in therapeutic use to date. PMID- 22775208 TI - Novel actions of progesterone: what we know today and what will be the scenario in the future? AB - OBJECTIVES: This article is aimed to review the novel actions of progesterone, which otherwise is considered as a female reproductive hormone. The article focuses on its important physiological actions in males too and gives an overview of its novel perspectives in disorders of central and peripheral nervous system. KEY FINDINGS: Progesterone may have a potential benefit in treatment of traumatic brain injury, various neurological disorders and male related diseases like benign prostatic hypertrophy (BPH), prostate cancer and osteoporosis. Norethisterone (NETA), a progesterone derivative, decreases bone mineral loss in male castrated mice suggesting its role in osteoporosis. In the future, progesterone may find use as a male contraceptive too, but still needs confirmatory trials for safety, tolerability and acceptability. Megestrol acetate, a progesterone derivative is preferred in prostatic cancer. Further, it may find utility in nicotine addiction, traumatic brain injury (recently entered Phase III trial) and Alzheimer's disease, diabetic neuropathy and crush injuries. Studies also suggest role of progesterone in stroke, for which further clinical trials are needed. The non genomic actions of progesterone may be in part responsible for these novel actions. SUMMARY: Although progesterone has shown promising role in various non-hormonal benefits, further clinical studies are needed to prove its usefulness in conditions like stroke, traumatic brain injury, neuropathy and crush injury. In male related illnesses like BPH and prostatic Ca, it may prove a boon in near future. New era of hormonal male contraception may be initiated by use of progesterone along with testosterone. PMID- 22775209 TI - Targeted gene delivery to hepatocytes with galactosylated amphiphilic cyclodextrins. AB - OBJECTIVES: Achieving targeted delivery of gene medicines is desirable to maximise activity. Here, galactosylated amphiphilic cyclodextrins (CDs) are examined in terms of their ability to transfect asialoglycoprotein receptor bearing HepG2 cells. METHODS: Cationic amphiphilic CDs were synthesised as well as amphiphilic CDs bearing galactose-targeting ligands with different linker lengths. Binding of galactosylated CDs to a galactose-specific lectin was examined by surface plasmon resonance. CDs were formulated with and without the helper lipid DOPE and complexed with plasmid DNA. Transfection was evaluated by luciferase assay. Intracellular trafficking was assessed by confocal microscopy. KEY FINDINGS: Binding of targeted CDs to a galactose-specific lectin was achieved. Binding decreased with linker length between the galactosyl group and the CD core. Contrary to the lectin binding results, transfection levels increased with an increase in linker length from 7 atoms to 15. Compared to non targeted formulations, a significant increase in transfection was observed only in the presence of the helper lipid DOPE. Confocal microscopy revealed that DOPE caused a pronounced effect on cellular distribution. CONCLUSIONS: The galactose targeting ligand induced substantial increases in transfection over non-targeted formulations when DOPE was included, indicating the potential for targeted gene delivery using CD-based delivery systems. PMID- 22775210 TI - Characterization of efflux transport of the PDE5 inhibitors, vardenafil and sildenafil. AB - OBJECTIVES: We aimed to characterize the efflux transport properties of vardenafil and sildenafil, and to compare the kinetics of these compounds via efflux transporters such as P-gp, BCRP and MRP2. METHODS: We measured the basal to-apical and apical-to-basal transport of vardenafil and sildenafil within the concentration range of 1-100 um using MDCKII cells overexpressing P-gp, BCRP and MRP2, and Caco-2 cells. KEY FINDINGS: Vardenafil had a much greater basal-to apical than apical-to-basal transport rate in MDCKII cells overexpressing P-gp, BCRP and MRP2. Sildenafil showed P-gp- and BCRP-mediated efflux transport, but did not seem to be pumped out via MRP2 transporters. Consequently, the absorptive transport of vardenafil and sildenafil in Caco-2 cells increased linearly over the concentration range of 1-100 um, whereas the secretory transport of these drugs was saturable and inhibited by the presence of specific inhibitors of P-gp and BCRP. MK571, a representative MRP2 inhibitor, inhibited the basal-to-apical transport of vardenafil, but not of sildenafil. CONCLUSION: The involvement of P gp, BCRP and MRP2 for vardenafil and the involvement of P-gp and BCRP for sildenafil in the secretory transport with linear absorptive transport may contribute to the limited intestinal absorption of these drugs. PMID- 22775211 TI - delta-Opioid receptor agonist SNC80 induces central antinociception mediated by Ca2+ -activated Cl- channels. AB - OBJECTIVES: The aim of this study was to determine whether Ca(2+)-activated Cl(-) channels (CaCCs) are involved in central antinociception induced by the activation of u-, delta- and kappa-opioid receptors. METHODS: The nociceptive threshold for thermal stimulation was measured using the tail-flick test in Swiss mice. The drugs were administered via the intracerebroventricular route. Probabilities values of P < 0.05 were considered to be statistically significant (analysis of variance/Bonferroni test). KEY FINDINGS: The results demonstrate that exposure to the CaCC blocker niflumic acid (2, 4 and 8 ug) partially reverses the central antinociception induced by the delta-opioid receptor agonist SNC80 ((+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3 methoxybenzyl]-N,N-diethylbenzamide; 4 ug). In contrast, niflumic acid did not modify the antinociceptive effect of the u-opioid receptor agonist [D-Ala(2), N Me-Phe(4), Gly(5)-ol]-enkephalin (0.5 ug) or kappa-opioid receptor agonist bremazocine (4 ug). CONCLUSIONS: These data provide evidence for the involvement of CaCCs in delta-opioid receptor-induced central antinociception resulting from receptor activation by the agonist SNC80. CaCC activation does not appear to be involved when u- and kappa-opioid receptors are activated. PMID- 22775212 TI - EP4 receptor signalling in immature B cells involves cAMP and NF-kappaB dependent pathways. AB - OBJECTIVES: Delineation of EP4 receptor signalling properties in immature B cells. METHODS: WEHI 231 cells were used as a model of immature B lymphocytes. The effects of PGE2, EP4 receptor antagonist, EP4 receptor agonist, forskolin and adenylate cyclase inhibitor on proliferation of WEHI 231 cells were examined by MTS assay. Cyclic adenosine monophosphate (cAMP) levels were examined by ELISA, whereas phosphorylation of vasodilator-stimulated phosphoprotein (VASP), kinase, extracellular signal-regulated kinase1/2, IkappaB-alpha and nuclear factor (NF) kappaB subunit p105 were subjected to Western blot analysis. Translocation of NF kappaB subunit p65 and EPRAP (EP4 receptor associated protein) was examined by fluorescence microscopy. Levels of early growth response factor (Egr)-1 mRNA were determined by quantitative PCR. KEY FINDINGS: We identified the EP4 receptor as the principal molecule mediating the growth-suppressive effect of prostaglandin E2 in WEHI 231 cells. EP4 receptor activation results in cAMP formation and the activation of protein kinase A, NF-kappaB1 p105 subunit stabilization and inhibition of IkappaBalpha phosphorylation, followed by the accumulation of NF kappaB p65 subunit in the cell cytoplasm, whereas the activation of PI3K is not involved in EP4 receptor signalling. Elevation of cAMP and inhibition of NF kappaB activation are two possible mechanisms by which the EP4 receptor inhibits the proliferation of immature B lymphocytes. CONCLUSIONS: Modulation of the EP4 receptor on immature B lymphocytes provides important insight into the observed action of PGE2 and opens new possibilities for the development of therapies for autoimmune diseases, leukaemia and lymphomas. PMID- 22775213 TI - Assessment of the pharmacological properties of 5-methoxyindole derivatives at 5 HT4 receptors. AB - OBJECTIVES: The aim was to examine the biological activity of 5-methoxytryptamine derivatives at the 5-hydroxytryptamine (5-HT)(4) receptor to explore the effect of substitution on the aliphatic amine of the 5-methoxyamine scaffold. METHODS: Three compounds were tested for affinity at the 5-HT(4) receptor by radioligand binding and functional activity using guinea-pig ileum and human colon circular muscle preparations and also in the mouse whole gut transit test. KEY FINDINGS: The three compounds all had agonist properties at the 5-HT(4) receptor but their efficacy differed in the different functional tests. Compound 3 had the highest affinity for the 5-HT(4) receptor and was a full agonist at relaxing human colon circular muscle with efficacy closest to 5-HT. Compounds 1 and 2 were partial agonists in this assay with lower efficacies; compound 2 was a full agonist in the guinea-pig ileum assay whereas compound 3 was a partial agonist. Compounds 1 and 2 also showed activity in the mouse gut transit assay while compound 3 had no activity. CONCLUSIONS: Of the compounds tested, compound 3 was the most promising 5-HT(4) receptor agonist and the results highlight the value of using human tissue in functional tests when assessing compounds for potential activity. PMID- 22775214 TI - Regulation of endothelial nitric oxide synthase and asymmetric dimethylarginine by matrine attenuates isoproterenol-induced acute myocardial injury in rats. AB - OBJECTIVES: This study was designed to investigate the cardioprotective effects of matrine on regulation of endothelial nitric oxide synthase (eNOS) and asymmetric dimethylarginine (ADMA) in isoproterenol-induced acute myocardial ischaemic rats. METHODS: Male Sprague-Dawley rats were pretreated with matrine (200, 100 and 50 mg/kg) orally for 10 days. Acute myocardial injury was induced in rats by subcutaneous injection of isoproterenol. Serum and haemodynamic parameters, histopathological variables and expression of protein levels were analysed. KEY FINDINGS: Oral administration of matrine (200, 100 and 50 mg/kg) significantly attenuated isoproterenol-induced cardiac necrosis and left ventricular dysfunction. Matrine treatment restored impaired ventricular Akt and eNOS protein expression with concomitant increased phosphorylation of Akt (Ser473) and eNOS (Ser1177), and also restored glycogen synthase kinase 3beta activity, as indicated by increased phosphorylation at Ser 9. Moreover, treatment with matrine had no effect on the isoproterenol-induced elevated protein arginine methyltransferase 1 protein expression, but could significantly normalize the reduced dimethylarginine dimethylaminohydrolase 2 expression and attenuate the increased serum level of ADMA. The expression of catechol-o-methyltransferase and monoamine oxidase did not differ among all groups (all P > 0.05). CONCLUSIONS: Our results suggested that matrine protects against isoproterenol-induced myocardial ischaemia via eNOS and ADMA pathway. PMID- 22775215 TI - Therapeutic properties of quercetin on monosodium urate crystal-induced inflammation in rat. AB - OBJECTIVES: Gouty arthritis is characterized by intense, acute inflammatory reactions that occur in response to articular deposits of monosodium urate crystals. In this study we have assessed the effects of the flavonoid, quercetin, on monosodium urate crystal-induced inflammation in rats, an experimental model for gouty arthritis. METHODS: Gouty arthritis was induced by intra-articular injection of monosodium urate crystal suspension inside the ankle joint of the rat right hind limb. Circumference was assessed at 2, 4, 8, 12, 24, and 48 h after monosodium urate crystal injection. Histopathological analysis of joint synovial tissue, inflammatory mediator levels, lipid peroxidation, and antioxidant status in serum, liver and joint synovial tissue were determined in control and monosodium urate crystal-treated rats at the end of experiment. KEY FINDINGS: Quercetin treatment attenuated oedema in a dose-dependent manner and decreased histological signs of acute inflammation in the treated animals. In addition, quercetin treatment suppressed leucocyte recruitment, decreased chemokine levels, decreased levels of the lipid peroxidation end-product malondialdehyde, and increased antioxidant enzyme activity in treated rats. CONCLUSIONS: These results indicated that quercetin exerted a strong anti inflammatory effect that may be useful for the treatment of acute gouty arthritis. PMID- 22775216 TI - The chick chorioallantoic membrane imaging method as a platform to evaluate vasoactivity and assess irritancy of compounds. AB - OBJECTIVE: To determine if the chick chorioallantoic membrane (CAM) is a potential alternative that is capable of screening test substances for vasoactivity in terms of vessel diameter changes. The CAM was also evaluated as a tool for irritancy screening. METHODS: Visual assessment of the CAM for irritancy after the application of the test substance or solvent to its surface was made. An imaging based-in-vivo CAM model was developed by imaging CAM blood vessels in a pre-defined area using a semi-automatic image processing and analysis technique to measure blood vessel diameters. Solvents and drugs such as 70% v/v ethanol, normal saline, 5% w/v glucose monohydrate, glycerin, glucagon, N methylpyrrolidone, nicotine, glyceryl trinitrate, glucagon, propranolol and caffeine were tested on the CAM. KEY FINDINGS: Propranolol, nicotine and glycerin were irritants on CAM. Changes in the diameters of fine blood vessels were accurately measured by high resolution image analysis. Vasoconstriction was seen with 70% v/v ethanol while vasodilation was displayed with glucagon and caffeine. The results reflected expected trends with evidence of feedback mechanisms ensuring homeostasis. CONCLUSION: The CAM model can be applied to assess pharmaceutical and cosmetic formulations in early development work to gain useful insights to potential irritancy and biological effects of components and formulations. PMID- 22775217 TI - Activation of AQP4, p66Shc and endoplasmic reticulum stress is involved in inflammation by carrageenan and is suppressed by argirein, a derivative of rhein. AB - OBJECTIVES: We investigated the effect of argirein on acute inflammation edema and examined that aquaporin 4 (AQP4), p66Shc and activating transcription factor (ATF-6) might be involved in carrageenan-induced rat paw inflammation and be reversed by argirein, rhein and indometacin, but not L-arginine. METHODS: Inflammation was produced by carrageenan injected into rat paw and treated orally with argirein (100 mg/kg), rhein (100 mg/kg), L-arginine (100 mg/kg) or indometacin (5 mg/kg). Inflammatory oedema and biomarkers were examined. KEY FINDINGS: Swelling was reduced by argirein, rhein and indometacin; argirein was more effective than rhein at 1 h following medication. Activation of AQP4, p66Shc, ATF-6, NADPH oxidase subunits p22phox, gp91phox and matrix metalloproteinase 2 (P < 0.01) was significant and was suppressed by arginine, rhein and indometacin but not by l-arginine. CONCLUSIONS: Activated AQP4, endoplasmic reticulum stress and p66Shc were actively implicated in the inflammation and these were suppressed by argirein, and its activity is favorable due to synergism in combination with L-arginine. PMID- 22775218 TI - Anti-tumour effects of elatol, a marine derivative compound obtained from red algae Laurencia microcladia. AB - OBJECTIVES: This paper aims to evaluate the anti-tumour properties of elatol, a compound (sesquiterpene) isolated from algae Laurencia microcladia. METHODS: In vitro and in-vivo anti-tumour properties of elatol were investigated using: MTT assays to assess the cytotoxic effects; flow cytometry analysis to examine the cell cycle and apoptosis; Western blot analysis for determination of the expression of cell cycle and apoptosis proteins; and study of in-vivo tumour growth in mice (C57Bl6 mice bearing B16F10 cells). KEY FINDINGS: Elatol exhibited a cytotoxic effect, at least in part, by inducing cell cycle arrest in the G(1) and the sub-G(1) phases, leading cells to apoptosis. Western blot analysis demonstrated that elatol reduced the expression of cyclin-D1, cyclin-E, cyclin dependent kinase (cdk)2 and cdk4. A decrease in bcl-xl and an increase in bak, caspase-9 and p53 expression was also observed. In the in-vivo experiment, treatment with elatol was able to reduce tumour growth in C57Bl6 mice. CONCLUSIONS: Elatol promotes a delay in the cell cycle, probably in the G(1)/S transition, activating the apoptotic process and this could be responsible, at least in part, for the in-vivo effects observed. Taken together, the in-vitro and in-vivo experiments suggested that elatol has anti-tumour properties. Further studies should be conducted to clarify the mechanism of action. PMID- 22775219 TI - Antispasmodic effects of a new kaurene diterpene isolated from Croton argyrophylloides on rat airway smooth muscle. AB - OBJECTIVES: The effects of rel-(1S,4aS,7S,8aS)-7-(1-vinyl)-tetradecahydro-1,4a dimethylphenanthrene-7,8a-carbolactone-1-carboxylic acid (TCCA), a new ent kaurene diterpene isolated from Croton argyrophylloides, on rat tracheal preparations were investigated. METHODS: Tracheae were removed and cut into two cartilage segments that were mounted in organ baths containing Tyrode's solution. RESULTS: TCCA reduced the contractions induced by electrical field stimulation, relaxed K(+)-induced contractions, and inhibited both phasic and tonic components of the K(+)- and ACh-induced contractions. TCCA reduced the serotonin-induced contraction, abolished that evoked by K(+) in the presence of epinephrine, and also reduced the ACh-induced contractions under Ca(2+)-free conditions. TCCA blocked contractions that depend on divalent cation inflow through voltage operated Ca(2+) channels (VOCCs) and receptor-operated Ca(2+) channels (ROCCs), but had greater potency to block VOCC- than ROCC-dependent contractions or contractions induced by ACh in Ca(2+)-free conditions. TCCA relaxed the phorbol 12,13 dibutyrate (1 um) induced contraction, but with slight potency. CONCLUSIONS: TCCA induces an antispasmodic effect through several mechanisms including blockade of either VOCCs (with greater potency) or ROCCs, blockade of IP(3)-induced Ca(2+) release from sarcoplasmic reticulum (with intermediate potency) and reduction of the sensitivity of contractile proteins to Ca(2+). PMID- 22775220 TI - beta-Cryptoxanthin suppresses UVB-induced melanogenesis in mouse: involvement of the inhibition of prostaglandin E2 and melanocyte-stimulating hormone pathways. AB - OBJECTIVE: beta-cryptoxanthin (beta-CPX) is a carotenoid that is widely contained in the fruits of citrus plants. We evaluated the effect of beta-CPX on UVB induced pigmentation and mRNA expression related to melanogenesis in mouse skin. In addition, changes in melanogenic molecules were evaluated in cultured melanocytes stimulated with prostaglandin (PG) E(2), melanocyte-stimulating hormone (MSH) and endothelin (ET)-1. METHODS: Mice were irradiated with UVB and were given beta-CPX (0.1, 1 and 10 mg/kg) orally for 14 days. Pigmentation was evaluated by skin colour change and microscopic observation. Total RNA was obtained from the skin and the expression of melanogenic mRNA was evaluated by RT PCR. In cell culture studies, human melanocytes were cultured with beta-CPX and melanogenic stimulants (PGE(2), MSH and ET-1) for 6-10 days. Melanin contents, dendricity, melanogenic mRNA and phosphorylation of cyclic AMP response element binding protein (CREB) were evaluated. KEY FINDINGS: beta-CPX (10 mg/kg) significantly suppressed skin pigmentation and mRNA expression of cyclooxygenase 2, ET-1 receptors, low-affinity neurotrophin receptor, PGE(2) receptor (EP1), melanocortin 1 receptor (MC1R), tyrosinase (Tyr), tyrosinase-related protein (Tyrp) 1 and microphthalmia transcription factor. beta-CPX (10 ug/ml) suppressed melanogenesis induced by PGE(2), MSH and ET-1. In the PGE(2)-stimulated melanocytes, mRNA expressions of EP-1, Tyr and Tyrp1 and phosphorylation of CREB protein were suppressed. In the ET-1-stimulated cells, only expression of CREB protein was suppressed. In the MSH-induced cells, mRNA expression of MC1R and Tyrp1 and protein expression of CREB were suppressed. CONCLUSION: Oral administration of beta-CPX was found to suppress UVB-induced melanogenesis. Suppression of melanogenic enzymes, receptors of melanogenic stimulators, expression and phosphorylation of CREB are thought to be involved in the mechanism. PMID- 22775221 TI - Hydroxyl scavenging activity accounts for differential antioxidant protection of Plantago major against oxidative toxicity in isolated rat liver mitochondria. AB - OBJECTIVES: The aim of this work was to study the effects of P. major against the oxidative damage of isolated rat liver mitochondria. METHODS: The extracts were obtained using methanol (MeOH), ethyl acetate (EAc), dichloromethane (DCM), and hexane (Hex) as solvents. KEY FINDINGS: Hex, DCM, and EAc totally, and MeOH partially, inhibited ROS generation and lipid peroxidation of membranes induced by Fe(2+) or t-BOOH. However, only MeOH was able to prevent the t-BOOH-induced glutathione and NAD(P)H oxidation. All extracts chelated Fe(2+) and reduced DPP Hradicals. EPR analysis revealed that P. major exhibited potent scavenger activity for hydroxyl radicals. CONCLUSIONS: The potent antioxidant activity exhibited by P. major was able to prevent oxidative mitochondrial damage, contributing to the understanding of its hepatoprotective action against ROS mediated toxicity. PMID- 22775222 TI - Ajuga iva aqueous extract improves reverse cholesterol transport in streptozotocin-induced diabetic rat. AB - OBJECTIVES: The aim of this study was to determine the effects of Ajuga iva aqueous extract on lecithin : cholesterol acyltransferase (LCAT) activity and amount and composition of high-density lipoprotein (HDL)(2) and (HDL)(3), in streptozotocin (STZ)-induced diabetic rats. METHODS: Diabetes was induced in male Wistar rats by intraperitoneal injection of STZ (60 mg/kg body weight). Diabetic rats (n = 12) were divided into two groups. The diabetic control group (D) received a 20% casein diet and the diabetic treated group received the same diet supplemented with A. iva aqueous extract (0.5 g/100 g diet) (DAi), for 4 weeks. KEY FINDINGS: Total cholesterol and HDL(3) -C were respectively decreased by 32% and 55% in the DAi group compared with the D group, whereas HDL(2)-C was increased by 30%. The amounts of HDL(2) and HDL(3), which were the sum of apolipoproteins, unesterified cholesterol (UC), cholesteryl esters (CEs), triacylglycerols (TGs) and phospholipids (PLs), showed no significant difference. A. iva treatment increased LCAT by 33% and its cofactor-activator, apolipoprotein A-I, by 58%. HDL(3)-PL (enzyme substrate) and HDL(3)-UC (acyl group acceptor) were respectively decreased by 70% and 57%, whereas HDL(2)-CE (product of LCAT reaction) was enhanced by 30%. CONCLUSIONS: In STZ-induced diabetic rats, A. iva improves reverse cholesterol transport by enhancing LCAT activity, leading to anti-atherogenic effects. PMID- 22775223 TI - Chemopreventive evaluation of Tephrosia purpurea against N-nitrosodiethylamine induced hepatocarcinogenesis in Wistar rats. AB - OBJECTIVES: The chemopreventive potential of Tephrosia purpurea extract (TPE) on N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma (HCC) in Wistar rats was assessed. METHODS: HCC was induced by a single intraperitoneal injection of NDEA (200 mg/kg) followed by subcutaneous injections of CCl(4) (3 ml/kg per week) for six weeks. After administration of the carcinogen, 200 and 400 mg/kg TPE were administered orally once a day throughout the study. KEY FINDINGS: The levels of liver cancer markers, including alpha-fetoprotein and carcinoembryonic antigen, were substantially increased by NDEA treatment. TPE treatment significantly reduced liver injury and restored the entire liver cancer markers. Additionally, TPE markedly normalized the activity of antioxidant enzymes, namely lipid peroxidation, reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase in the liver of NDEA-treated rats. Treatment with TPE significantly reduced the nodule incidence and multiplicity in the carcinogen-bearing rats. Histological observations of the liver tissues correlated with the biochemical observations. CONCLUSIONS: These findings powerfully support that T. purpurea prevented lipid peroxidation, suppressed the tumour burden, and promoted enzymatic and nonenzymatic antioxidant defence systems during NDEA-induced hepatocarcinogenesis. This might have been due to modulating the antioxidant defence status, which contributed to its anticarcinogenic potential. PMID- 22775224 TI - Enteroaggregative Escherichia coli pathotype: a genetically heterogeneous emerging foodborne enteropathogen. AB - Until now, a common feature that defines the enteroaggregative Escherichia coli (EAEC) strains is the ability to produce a 'stacked-brick' appearance on epithelial cells, but it does not distinguish between pathogenic and nonpathogenic strains. Numerous adhesins, toxins, and proteins associated with virulence have been described, as well as multiple factors contributing to EAEC induced inflammation. None of these factors are found in all EAEC isolates, and no single factor has ever been implicated in EAEC virulence. The European outbreak of Shiga-toxin-producing EAEC raises its pathogenic potential and interest on finding the true pathogenic factors that may define this pathotype. EAEC were first associated with persistent diarrhea in infants from developing countries, since then they have increasingly been linked as a cause of acute and persistent diarrhea in young infants and children in developing and industrialized countries, individuals infected with human immunodeficiency virus, as a cause of acute diarrhea in travelers from industrialized regions, and with foodborne outbreaks. A major effect of EAEC infection is on the malnourished children in developing countries. Here, we will discuss the EAEC public health relevance and their complexity because of the strain heterogeneity regarding their pathogenesis, identification, diagnosis, lineage, epidemiology, and clinical manifestations. PMID- 22775225 TI - High frequency of CAM use among children in Germany. PMID- 22775226 TI - A longitudinal study of the intra-country variations in the provision of residential care for adult persons with an intellectual disability. AB - BACKGROUND: Small-scale community accommodation is the preferred alternative internationally to the institutional and congregated services that previously dominated residential care for persons with intellectual disability. The strategies required for changing to new service models are not well researched. METHOD: The National Intellectual Disability Database in Ireland provided the data to explore the changes in provision that occurred over a 10-year period and the extent of the intra-country variation across eight administrative areas for health services. Data were extracted for 2 years, 1999 and 2009, for over 7000 adult persons resident in either congregated or community-based accommodation. Comparative indicators were calculated for the eight areas as well as nationally. In addition, over 4000 persons living in congregated settings were tracked over the 10 years to ascertain relocations as well as gathering information on the numbers of people newly admitted to each type of accommodation. RESULTS: Marked variations across the eight areas were found in the overall numbers of people in residential accommodation, the proportion of persons living in congregated settings and the extent of changes in the numbers of people in each type of accommodation. Moreover, fewer than 15% of people had relocated nationally from congregated settings over the 10-year period and the number of new admissions to this form of provision remained high in certain areas. CONCLUSIONS: The implementation of new forms of provision was not uniform across Ireland and possible reasons are proposed. Among the wider lessons internationally is the need for robust systems to monitor service provision nationally and locally if equity of access is to be achieved. PMID- 22775228 TI - Synthesis and ultrafast excited-state dynamics of zinc and palladium triply fused diporphyrins. AB - We report the synthesis and ultrafast excited-state dynamics of two new meso meso, beta-beta, beta-beta triply fused diporphyrins, Zn-3DP and Pd-3DP. Both compounds were found to have short excited-state lifetimes: Zn-3DP possessed an average S1 lifetime of 14 ps before nonradiative deactivation to the ground state, whereas Pd-3DP displayed a longer average S1 lifetime of 18 ps before crossing to the T1 state, which itself possessed a very short triplet lifetime of 1.7 ns. The excited-state dynamics of Zn-3DP, compared to similar zinc(II) diporphyrins reported in the literature, suggests that a conical intersection of the S1 and S0 potential energy surfaces plays a major role as a deactivation pathway of these molecules. Furthermore, the short triplet lifetime of Pd-3DP, compared to other diporphyrins that also exploit the intramolecular heavy atom effect, reveals that the position of the heavy atom within the diporphyrin framework influences the strength of spin-orbit coupling. The implications for employing triply fused diporphyrins as NIR-absorbing triplet sensitizers are discussed. PMID- 22775227 TI - The influence of elastic modulus mismatch between tooth and post and core restorations on root fracture. AB - AIM: To investigate the influence of elastic modulus mismatch between tooth and post and core restorations on mechanisms of root fracture. METHODOLOGY: Three dimensional mathematical models of a root filled maxillary premolar tooth with supporting periodontium were constructed. The tooth was restored with a cast Ni Cr alloy or fibre-reinforced composite post and core that was bonded or nonbonded to dentine. In the nonbonded simulation, a nonlinear contact analysis was executed to simulate a friction and a potential sliding phenomenon in the interface between tooth and post and core. Risks of root fracture and debonding at the bonded interface were estimated based on the principal stress of the root and the shear stress on the interface, respectively. RESULTS: The fracture risk of the bonded cast post and core was lower than that of the composite post and core, although the cast restoration exhibited eight times greater stress than the composite. The risk of root fracture based on the tensile stress of the tooth structures was higher with the bonded composite post and core than that with the cast post and core. These stresses doubled when the restorations were not bonded to the tooth structures. The risk of debonding of the cast post and core based on the shear stress was approximately twice that of the composite post and core. CONCLUSIONS: The elastic modulus mismatch appears to be a factor responsible for the debonding of post and cores from root canals, with the potential to increase the risk of root fracture indirectly. PMID- 22775229 TI - A double-masked randomized crossover study comparing the effect of latanoprost/timolol and brimonidine/timolol fixed combination on intraocular pressure and ocular blood flow in patients with primary open-angle glaucoma or ocular hypertension. AB - PURPOSE: Ocular blood flow dysregulation has been implicated in the pathogenesis of glaucoma. Whereas the effect of single antiglaucoma substances on ocular blood flow has been addressed in various experiments, evidence for fixed combinations is sparse. In the present study, we set out to compare the effects of latanoprost 0.005%/timolol 0.5% (LT) fixed combination and brimonidine 0.2%/timolol 0.5% (BT) fixed combination on intraocular pressure (IOP) and ocular blood flow. METHODS: In the present study, which followed a randomized, double-masked 2-way crossover design, 16 patients with primary open-angle glaucoma and 2 patients with ocular hypertension were included. The patients underwent a 6-week treatment with LT and a 6-week treatment with BT after a washout for previous antiglaucoma medication. Optic nerve head blood flow (ONHBF) was measured using laser Doppler flowmetry; retrobulbar flow velocities were measured using color Doppler imaging in the ophthalmic artery, the central retinal artery, and the posterior ciliary arteries. IOP was measured at 8 AM, 12 PM, and 4 PM. RESULTS: The mean baseline IOP was 25.3+/-2.8 mmHg. Both drugs were equally effective in reducing IOP (LT: 35.0%+/-10.0%; BT: -33.6%+/-8.8%, P=0.463 between groups). In addition, no difference in ocular perfusion pressure was observed between the 2 treatment groups (P=0.1, between groups). Neither LT nor BT altered ONHBF (P=0.4, baseline vs. treatment) and no effect on flow velocities in the retrobulbar vessels was seen with either of the 2 treatments. CONCLUSIONS: In the present study, a 6-week treatment with LT or BT was equally effective in reducing IOP. In addition, none of the administered drugs induced a significant effect on ocular blood flow parameters. PMID- 22775230 TI - Irradiation induced grain boundary flow--a new creep mechanism at the nanoscale. AB - A new mechanism of irradiation enhanced creep is proposed for nanocrystalline materials. It derives from local relaxations within the grain boundaries as they absorb point defects produced by irradiation. The process is studied by inserting point defects into the grain boundaries and following the materials response by molecular dynamics. Calculated creep compliances are found in good agreement with those measured in dilute nanocrystalline Cu-W alloys [Tai, K.; Averback, R. S.; Bellon, P.; Ashkenazy Y. Scr. Mater.2011, 65, 163]. The simulations provide a direct link between irradiation induced creep in nanocrystalline materials with radiation-induced viscous flow in amorphous materials, suggesting that grain boundaries in these materials can be treated as an amorphous phase. We provide a simple analytic model based on this assumption that reproduces the main features of the observed creep rates, a linear dependence on stress, inverse dependence of grain size, a weak dependence on temperature, and a reasonable estimate of the absolute creep rate. PMID- 22775231 TI - Rationale and pitfalls of noninvasive coronary flow reserve estimation in assessment of microvascular disease. PMID- 22775233 TI - XVII World Congress of Echocardiography, Vascular Ultrasound and Allied Techniques March 8-10, 2012 Sao Paulo, Brazil. PMID- 22775234 TI - Childhood physical abuse is associated with incident metabolic syndrome in mid life women. AB - OBJECTIVE: Previous research has suggested that childhood emotional abuse, physical abuse, and sexual abuse are associated with an increased risk for ischemic heart disease. Our objective was to examine whether childhood abuse predicted incident metabolic syndrome, a precursor to heart disease, in midlife women. METHODS: Participants were 342 (114 Black, 228 White) women from the Pittsburgh site of the Study of Women's Health Across the Nation (SWAN). SWAN included a baseline assessment of premenopausal or early perimenopausal women in midlife (mean age = 45.7), and women were evaluated for presence of the metabolic syndrome over 7 annual follow-up visits. Women were classified as having metabolic syndrome if they met 3 of the following criteria: waist circumference >88 cm, triglycerides >=150 mg/dl, HDL <50 mg/dl, SBP >=130 or DBP >=85 mmHg or on blood pressure medication, and fasting glucose >=110 mg/dl or diabetic. The Childhood Trauma Questionnaire is a standardized measure that retrospectively assesses 3 domains of abuse in childhood and adolescence: emotional, physical, and sexual abuse. RESULTS: Approximately 34% of the participants reported a history of abuse. Cox model survival analysis showed that physical abuse was associated with incident metabolic syndrome over the course of 7 years (HR = 2.12, p = .02), adjusted for ethnicity, age at baseline, and time-dependent menopausal status. Sexual abuse and emotional abuse were unrelated to the metabolic syndrome. CONCLUSION: This is the first study to show that a history of childhood abuse, specifically physical abuse, is related to the development of metabolic syndrome in midlife women. PMID- 22775236 TI - Smoker identity and smoking escalation among adolescents. AB - OBJECTIVE: We investigated whether there is a positive, unique relation between smoker identity and smoking escalation. METHODS: Adolescents from the Chicago area (n = 1263) completed paper-and-pencil questionnaires and in-person interviews at baseline, 6 months, 15 months, and 24 months of a longitudinal study. Smoking behavior, smoker identity, nicotine dependence, smoking expectancies, smoking motives, and novelty seeking were assessed. RESULTS: There was a unique relation between smoker identity and smoking escalation. The more that adolescents thought smoking was a defining aspect of who they were, the more likely their smoking escalated. CONCLUSIONS: The findings suggest that smoker identity could be targeted for preventing escalation. Research on its development is needed. PMID- 22775237 TI - Operationalizing treatment as prevention in Los Angeles County: antiretroviral therapy use and factors associated with unsuppressed viral load in the Ryan White system of care. AB - Despite extensive prevention efforts, an estimated 21% of individuals with HIV/AIDS in the United States are unaware of their status, placing them at greater risk for spreading the virus to others. HIV treatment as prevention (TasP) is rapidly becoming an important public health strategy to reduce HIV transmission at the population level. Data for this study were collected on a sample of 11,397 HIV-positive individuals in the Ryan White system, a publicly funded system of care for HIV-positive individuals in Los Angeles County who are uninsured, in 2009 to examine two components of TasP: baseline rates and factors associated with antiretroviral therapy (ART) use and viral load (VL) suppression in a publicly funded system of care. ART coverage among our sample was 90%. In multivariate analyses, those with a higher odds of having unsuppressed VL included: females compared to males (adjusted odds ratio [AOR]=1.25; 95% confidence interval [CI]=1.06, 1.47); African Americans compared to whites (AOR=1.42; 95% CI=1.24, 1.62); men who have sex with men compared to heterosexuals (AOR=1.15; 95% CI=1.00, 1.32); recent substance abusers compared to nonsubstance abusers (AOR=1.35; 95% CI=1.17, 1.55); those recently incarcerated or ever incarcerated compared to those never incarcerated (AOR=1.37; 95% CI=1.15, 1.63; and AOR=1.28; 95% CI=1.09, 1.50); and those retained in care compared to those not retained in care (AOR=1.98; 95% CI=1.76, 2.22). Understanding the key sociodemographic, geographic and behavioral factors associated with ART use as well as HIV VL suppression will be useful for informing the development and deployment of targeted programming and policies that may further enhance the implementation of the TasP approach in communities across the United States. PMID- 22775239 TI - An oral TRPV1 antagonist attenuates laser radiant-heat-evoked potentials and pain ratings from UV(B)-inflamed and normal skin. AB - AIMS: Laser (radiant-heat) evoked potentials (LEPs) from vertex-EEG peak-to-peak (PtP) amplitude were used to determine acute antinociceptive/antihyperalgesic efficacy of ABT-102, a novel TRPV1 antagonist efficacious in preclinical pain models, compared with active controls and placebo in normal and UV(B)-inflamed skin. METHODS: This was a randomized, placebo- and active-controlled, double blind, intra-individual, crossover trial. Twenty-four healthy subjects received six sequences of single doses of ABT-102 (0.5, 2, 6 mg), etoricoxib 90 mg, tramadol 100 mg and placebo. Painful stimuli were induced by CO(2) -laser on normal and UV(B) -inflamed skin. LEPs and visual analogue scale (VAS-pain) ratings were taken at baseline and hourly up to 8 h post-dose from both skin types. RESULTS: Compared with placebo, significant mean decreases in the primary variable of LEP PtP-amplitude from UV(B)-inflamed skin were observed with ABT-102 6 mg (P < 0.001), ABT-102 2 mg (P = 0.002), tramadol 100 mg (P < 0.001), and etoricoxib 90 mg (P = 0.001) over the 8 h period; ABT-102 0.5 mg was similar to placebo. ABT-102 6 mg was superior to active controls over the 8 h period (P < 0.05) whereas ABT-102 2 mg was comparable. Improvements in VAS scores compared with placebo were observed with ABT-102 6 mg (P < 0.001) and ABT-102 2 mg (P = 0.002). ABT-102 average plasma concentrations were 1.3, 4.4 and 9.4 ng ml(-1) for the 0.5, 2 and 6 mg doses, respectively. There were no clinically significant safety findings. CONCLUSIONS: TRPV-1 antagonism appears promising in the management of clinical pain, but requires further investigation. PMID- 22775241 TI - What is wrong with quantitative structure-property relations models based on three-dimensional descriptors? AB - Quantitative structure-property relations (QSPR) employing descriptors derived from the three-dimensional (3D) molecular structure are frequently applied for property prediction in various fields of research. However, there is no common understanding of the necessary degree of detail to which molecular structure has to be known for reliable descriptor evaluation, but computational methods used vary from simplified molecular mechanics up to rigorous ab initio programs. In order to quantify the yet unknown error due to this heterogeneity, widely used 3D molecular descriptors from diverse fields of application are evaluated for molecular structures computed by different computational methods. The results clearly indicate that the widespread, exclusive use of the most stable molecular conformation as well as too simplistic computational methods yield systematically erroneous descriptor values with misleading information for the inferred structure-property relations. Thus, generating an awareness and understanding of this fundamental problem is considered an important first step to make 3D QSPR a generally accepted property prediction method. PMID- 22775240 TI - The association of self-monitoring of blood glucose use with medication adherence and glycemic control in patients with type 2 diabetes initiating non-insulin treatment. AB - BACKGROUND: The value of self-monitoring of blood glucose (SMBG) for persons with type 2 diabetes who do not use insulin remains controversial. This observational study compares the likelihood of medication adherence and change in glycated hemoglobin (A1C) for non-insulin-using patients using SMBG versus those not using SMBG. The study also assessed the association between diabetes medication adherence and SMBG use. PATIENTS AND METHODS: Data were extracted on 5,172 patients who began non-insulin diabetes medication between October 1, 2006, and March 31, 2009. The study assessed change in A1C associated with SMBG use and testing frequency at different categorical levels of baseline A1C. The likelihood of medication adherence for SMBG users was compared with that for non-SMBG users at different categorical levels of baseline A1C. The study further explored the interactions between SMBG use and medication adherence on change in A1C. RESULTS: SMBG users had greater reductions in A1C compared with nonusers when the baseline A1C was >= 7%. Increasing SMBG frequency was associated with greater reductions in A1C. The study also examined the associations among SMBG use, medication adherence, and change in A1C. SMBG users had greater decreases in A1C for both medication-adherent and -nonadherent patients. As expected, medication adherence was associated with greater reductions in A1C for both SMBG nonusers and users. It is interesting that medication-nonadherent SMBG users had similar reductions in A1C compared with medication-adherent non-SMBG users. CONCLUSIONS: Both SMBG use and medication adherence were associated with similar degrees of A1C reduction after controlling for baseline A1C, suggesting that both factors may be important for attaining glycemic control. PMID- 22775242 TI - Living kidney donor relationship in Caucasian and African American populations and implications for targeted donor education programs. AB - PURPOSE: The opportunities for living kidney donation vary greatly among socioeconomic and racial groups. We reviewed our series of living donors to evaluate donor relationships in various groups. MATERIALS AND METHODS: Donor and recipient records for 1000 patients were reviewed. An additional 857 records of potential recipients presenting with a donor were analyzed. We compared the relationship of the recipient to initial donor and individual who underwent nephrectomy. RESULTS: There were 693 CC and 263 AA live kidney donors. In the AA population donors were first-degree 71%, second-degree 10%, and unrelated 19%. In the CC population donors were first-degree 57%, second-degree 6%, and unrelated 37% (p < 0.0001 for unrelated CC vs. AA). Spousal donation is more common in CC donors (13%) than AA donors (6%), p = 0.001. Donation from child to parent is more common in AA (33%) than CC donors (15%), p < 0.0001. AA recipients predominantly identified a child as a donor in 63% and 48% were cleared for donation. In contrast, 69% of CC recipients identified a spouse as a donor yet only 23% became donors, p < 0.001 and p < 0.001. CONCLUSIONS: There is a higher incidence of unrelated donors in the caucasian population, vs. first degree relatives often being living donors in the AA population. PMID- 22775238 TI - Quantitative- and phospho-proteomic analysis of the yeast response to the tyrosine kinase inhibitor imatinib to pharmacoproteomics-guided drug line extension. AB - Imatinib mesylate (IM) is a potent tyrosine kinase inhibitor used as front-line therapy in chronic myeloid leukemia, a disease caused by the oncogenic kinase Bcr Abl. Although the clinical success of IM set a new paradigm in molecular-targeted therapy, the emergence of IM resistance is a clinically significant problem. In an effort to obtain new insights into the mechanisms of adaptation and tolerance to IM, as well as the signaling pathways potentially affected by this drug, we performed a two-dimensional electrophoresis-based quantitative- and phospho proteomic analysis in the eukaryotic model Saccharomyces cerevisiae. We singled out proteins that were either differentially expressed or differentially phosphorylated in response to IM, using the phosphoselective dye Pro-Q((r)) Diamond, and identified 18 proteins in total. Ten were altered only at the content level (mostly decreased), while the remaining 8 possessed IM-repressed phosphorylation. These 18 proteins are mainly involved in cellular carbohydrate processes (glycolysis/gluconeogenesis), translation, protein folding, ion homeostasis, and nucleotide and amino acid metabolism. Remarkably, all 18 proteins have human functional homologs. A role for HSP70 proteins in the response to IM, as well as decreased glycolysis as a metabolic marker of IM action are suggested, consistent with findings from studies in human cell lines. The previously-proposed effect of IM as an inhibitor of vacuolar H(+)-ATPase function was supported by the identification of an underexpressed protein subunit of this complex. Taken together, these findings reinforce the role of yeast as a valuable eukaryotic model for pharmacological studies and identification of new drug targets, with potential clinical implications in drug reassignment or line extension under a personalized medicine perspective. PMID- 22775243 TI - Substituted Iboga-alkaloids and their model receptor interactions - theoretical and experimental studies. PMID- 22775244 TI - Pyrolysis for biochar purposes: a review to establish current knowledge gaps and research needs. AB - According to the International Biochar Initiative (IBI), biochar is a charcoal which can be applied to soil for both agricultural and environmental gains. Biochar technology seems to have a very promising future. Nevertheless, the further development of this technology requires continuing research. The present paper provides an updated review on two subjects: the available alternatives to produce biochar from a biomass feedstock and the effect of biochar addition to agricultural soils on soil properties and fertility. A high number of previous studies have highlighted the benefit of using biochar in terms of mitigating global warning (through carbon sequestration) and as a strategy to manage soil processes and functions. Nevertheless, the relationship between biochar properties (mainly physical properties and chemical functionalities on surface) and its applicability as a soil amendment is still unclear and does not allow the establishment of the appropriate process conditions to produce a biochar with desired characteristics. For this reason, the need of enhancing the collaboration among researchers working in different fields of study is highlighted: production and characterization of biochar on one hand, and on the other measurement of both environmental and agronomical benefits linked to the addition of biochar to agricultural soils. In this sense, when experimental results concerning the effect of the addition of biochar to a given soil on crop yields and/or soil properties are published, details regarding the properties of the used biochar should be well reported. The inclusion of this valuable information seems to be essential in order to establish the appropriate process conditions to produce a biochar with more suitable characteristics. PMID- 22775245 TI - Disruption of neuropsin mRNA expression via RNA interference facilitates the photoinduced increase in thyrotropin-stimulating subunit beta in birds. AB - It has long been known that the avian brain is capable of light detection independently of the eyes. The photoreceptive molecule neuropsin (OPN5) was identified in mammalian and avian brains, and shown to respond to biologically relevant light wavelengths. Whether OPN5 is functionally involved in light detection is unknown. Daylength plays a critical role in regulating the neuroendocrine control of reproduction in birds. The presence of light during a 'photoinducible' phase of the circadian cycle, which occurs 12-16 h after dawn, results in marked changes in hypothalamic gene expression. These changes ultimately control gonadotropin release from the pituitary gland that, in turn, stimulates gonadal development. In this study, we first measured OPN5 expression in the mediobasal hypothalamus (MBH) in border canaries during the photoinducible period in relation to thyrotropin (TSH) beta-subunit mRNA expression, which is implicated in the control of avian reproduction. Second, the knockdown of OPN5 via small interfering RNA antisense in the MBH revealed that there is an inhibitory input in the photoinduced regulation of TSHbeta mRNA expression. Our data indicate that a decrease in OPN5 mRNA expression is associated with the facilitation in TSHbeta mRNA expression in the MBH, a critical step for the light induced increase in gonadal recrudescence. We hypothesise that the removal of an inhibitory input by OPN5 in birds may be a step that occurs during the photoinducible period. Given the distribution of OPN5 in the brain and periphery, this suggests a possible multifunctional role for light information in regulating other physiological processes. PMID- 22775246 TI - Effectiveness of psychiatric inpatient care. AB - There is a growing demand for evaluating the process and outcome of mental health care. Most healthcare providers routinely collect and register data related to the process of treatment, and it is important to acquire more knowledge about how to make use of these databases. The aim of this study was to investigate the outcome of psychiatric inpatient care in relation to different clinical factors, using the Global Assessment of Functioning Scale (GAF) as a measure of outcome. Another objective was to explore the ability of routinely collected and registered data to provide valuable information about patients and their care. The studied psychiatric inpatient sample consisted of 816 care episodes with GAF ratings made both at admission and at discharge for 648 patients. Variables used in the study included GAF score at admission and at discharge, age, gender, diagnosis, length of stay and ward affiliation. The overall mean GAF change was 20.74, and the overall effect size Cohen's d 1.67, which corresponds to a large effect. The mean GAF change for women was 21.6, with an effect size of 1.80, and for men 19.4 with an effect size of 1.52. The effect size spectra including all groups of diagnoses ranged from 1.03 (substance-related disorders) to 2.33 (other mood disorders). Length of stay and ward affiliation also showed significant results concerning GAF change. Some limitations in this study could depend on the absence of randomization procedures and a control group. Another limitation concerns the insufficient control of the inpatient care interventions performed. The results support the capacity of the GAF to function as a measure of outcome in relation to different clinical factors, such as length of stay and diagnosis. Support was also found for the importance and usefulness of routinely collected and registered data. PMID- 22775247 TI - The functional fitness capacity of adults with Down syndrome in South Africa. AB - BACKGROUND: It is well established that there is a relationship between physical inactivity and increased risk for diseases of lifestyle. Persons with Down syndrome (DS) are especially at risk because of physical and health impairments, as well as perceived and real barriers to participation in exercise. The purpose of the study was to establish the functional fitness capacity and predictors of performance of DS adults. METHODS: Data were collected at various intellectual disability centres and private homes in seven provinces of South Africa. Three hundred and seventy-one DS individuals (199 men and 172 women) from 18 to 66 years were tested for balance, flexibility, coordination, muscular strength and endurance, aerobic capacity and functional ability. Data were categorised according to gender and age groups (18-25, 26-35, 36-45, and >45 years). Multiple regression analysis was performed to determine the relationship between the functional task and physical test items. RESULTS: Down syndrome men performed significantly better on all but two tests compared with the women (P < 0.05). DS women performed better on the sit-and-reach flexibility item and the chair stand test; however, differences were not statistically significant from the men. Significant differences across age groups were observed for nine of the 13 functional fitness tests (P < 0.05). Muscular strength items, especially leg strength, significantly predicted functional performance in DS men and women. Aerobic capacity only predicted functional performance in DS men and sit-and reach flexibility and dynamic balance only in DS women. CONCLUSIONS: Findings of this study provide important information on the functional capacity of DS adults and show which physical attributes contribute to functional performance. Consequently appropriate training programmes can be tailored for this population whom is known to have poor functional fitness. PMID- 22775248 TI - Variation in russet sparrow (Passer cinnamomeus) breeding biology in relation to small-scale altitudinal differences in China. AB - Evolution of avian life histories is typically strongly influenced by both altitude and latitude. To date, most studies have investigated the effects of extreme differences in altitude and latitude on variation in reproductive traits. Studies based on small altitude and latitude spans are needed to better understand the resolution of selective pressures. We compared several aspects of russet sparrow (Passer cinnamomeus) breeding biology between a low-altitude (200 m) and a high-altitude (1,500 m) population in China, representing a relatively small altitudinal gradient (1,300 m). High-altitude birds initiated breeding significantly later compared to their low-altitude counterparts. Interestingly, breeding season was significantly longer in the high-altitude site (57 vs. 84 d). Lowland sparrows laid larger clutches (4.92 vs. 4.09 eggs) and showed greater fledging success (4.20 vs. 3.46 fledgings) than did upland birds. Variation in life history traits thus appears to occur even along a small scale altitudinal gradient. We suggest that the longer breeding season and smaller clutch size in the highland population may be an adaptation or acclimation to compensate for the reduced annual productivity resulting from unfavourable or sub-optimal habitats for these sparrows. PMID- 22775249 TI - Alarm signals of the Sichuan sika deer Cervus nippon sichuanicus. AB - Sichuan sika deer (Cervus nippon sichuanicus) is an endangered and endemic subspecies of sika deer to Sichuan Province, China. According to our observations in the wild, the Sichuan sika deer makes alarm signals in the presence of actual or potential predators. In order to test the variation of the rhythmic alarm calls in some sex/age classes and different risk contexts, we recorded alarm calls of Sichuan sika deer from 2 October to 30 November 2008 and from 4 April to 5 September 2009 in the Tiebu Nature Reserve, Zoige County, Sichuan Province, China, and made acoustic analysis of these alarm calls. The results showed that the fundamental frequencies of alarm signals of Sichuan sika deer tended to decrease with age, and were significantly higher for females than for males. Duration tended to increase with age, and was significantly longer for males than for females. The fundamental frequencies and duration of alarm calls in adults were significantly higher and shorter respectively in high-risk than in moderate risk contexts. PMID- 22775250 TI - Mating behavior and the function of the male genital spine in the ground beetle Carabus clathratus. AB - The morphologies of male genitalia often appear harmful or aggressive, as if they may inflict physical damage upon females during copulation. Such male genitalia are often thought to function in intra- and intersexual interactions during mating. In the carabid genus Carabus, division Spinulati, males possess a spine (spinula) on the intromittent organ, of which function is unknown. To reveal the function of the spinula, we studied the mating behavior and genital coupling of a Spinulati species, Carabus (Limnocarabus) clathratus. The males positioned the spinula along the inner wall of the vaginal opening throughout copulation. This placement created a small dent and subsequently a melanized patch (wound) on the vaginal wall, but the spinula rarely penetrated the vaginal wall. The spinula did not reach the innermost part of the vagina where the spermatophore is deposited. These results suggest that the spinula is not used for inflicting damage on female genitalia or manipulating spermatophores of rival males. During spermatophore formation, the male partially withdrew the aedeagus, and only the aedeagal tip and endophallus remained within the female. By placing the spinula against the vaginal wall, the male could hold the endophallus within the vaginal chamber in the unstable copulatory posture. Thus, our observations suggest that the spinula primarily functions as an "anchor" to maintain the coupling of the male and female genitalia and thereby ensure insemination. PMID- 22775251 TI - Genetic variation and population structure of the Japanese sika deer (Cervus nippon) in the Tohoku District based on mitochondrial D-loop sequences. AB - The sika deer (Cervus nippon) once inhabited the entire Tohoku District, the northeastern part of the main island of Japan. Currently, they are isolated as three discontinuous populations on Mt. Goyo, the Oshika Peninsula, and Kinkazan Island. To assess the genetic diversity and relationships among the sika deer populations in the Tohoku District, we analyzed the mitochondrial DNA D-loop sequences from 177 individuals. We detected a total of five haplotypes. Three haplotypes were present in the population from Mt. Goyo at a haplotype diversity of 0.235 +/- 0.061, two haplotypes in the population from the Oshika Peninsula at 0.171 +/- 0.064, and only one haplotype was detected in the population from the Kinkazan Island. A significant genetic differentiation was observed among all population pairs. Collectively, our data supports the observed population bottlenecks in the past. Four of the five haplotypes were specific to one of the three populations, whereas only one haplotype was shared between the Mt. Goyo and the Oshika Peninsula populations. This common haplotype may indicate a common ancestral population in the Tohoku District. Conversely, the D-loop haplotypes were completely different among the Kinkazan Island and Oshika Peninsula populations. The lack of a shared haplotype indicates that female gene flow between the two populations is very limited and that the 0.6 km strait acts as a strong barrier. PMID- 22775252 TI - Microvascularization on collared peccary placenta: a microvascular cast study [corrected] in late pregnancy. AB - The microvascularization of the collared peccary (Tayassu tajacu) placenta was studied by vascular casts and immunolocalization of alpha-smooth muscle actin and vimentin, to identify the three dimensional organization and vascular flow interrelation in the microvasculature between the maternal and fetal compartments of the placentae. The immunolocalization of vimentin in the vascular endothelium and in the smooth muscle cells of blood vessels showed indented capillaries along the uterine epithelium and the trophoblast at the sides of complementary maternal and fetal microfolds, or rugae. This confers the three-dimensional structure observed in vascular casts. On the maternal side, casts demonstrated uterine folds coated by with primary and secondary ridges, and by areolae dispersed between these ridges. The arteriole runs through the center/middle of ridges, branching at the top into a microvascular network wall in a basket-like fashion. At the base of these baskets venules were formed. On the fetal side, arterioles branched centrally in the fetal rugae into a capillary network in a bulbous form, complementary to the opposite maternal depressions forming the baskets. At the base of the bulbous protrusions, the fetal venules arise. The blood vessel orientation in the materno-fetal interface of the placentae of collared peccaries suggests a blood flow pattern of the type countercurrent to cross current. The same pattern has been reported in domestic swine demonstrating that, even after 38 million years, the Tayassuidae and Suidae families exhibit similar placental morphology, which is here characterized at the microvascular level. PMID- 22775253 TI - Morphological responses of mitochondria-rich cells to hypersaline environment in the Australian mudskipper, Periophthalmus minutus. AB - A population of the Australian mudskipper, Periophthalmus minutus, was found to inhabit mudflat that remained uncovered by tide for more than 20 days in some neap tides. During these prolonged emersion periods, P. minutus retreated into burrows containing little water, with a highest recorded salinity of 84 +/- 7.4 psu (practical salinity unit). To explore the mechanical basis for this salinity tolerance in P. minutus, we determined the densities of mitochondria-rich cells (MRCs) in the inner and outer opercula and the pectoral fin skin, in comparison with P. takita, [corrected] from an adjacent lower intertidal habitat, and studied morphological responses of MRCs to exposure to freshwater (FW), and 100% (34-35 psu) and 200% seawater (SW). Periophthalmus minutus showed a higher density of MRCs in the inner operculum (3365 +/- 821 cells mm(-2)) than in the pectoral fin skin (1428 +/- 161) or the outer operculum (1100 +/- 986), all of which were higher than the MRC densities in p. takita. [corrected]. No mortality occurred in 100% or 200% SW, but half of the fish died within four days in FW. Neither 200% SW nor FW exposure affected MRC density. Transfer to 200% SW doubled MRC size after 9-14 days with no change in the proportion of MRCs with apical pits or plasma sodium concentration. In contrast, transfer to FW resulted in a rapid closing of pits and a significant reduction in plasma sodium concentration. These results suggest that P. minutus has evolved morphological and physiological mechanisms to withstand hypersaline conditions that they may encounter in their habitat. PMID- 22775254 TI - Histochemical analyses of hepatic architecture of the hagfish with special attention to periportal biliary structures. AB - The hagfish liver was histochemically examined with special attention to biliary structures around the portal veins. Hepatocytes were organized into tubular structures surrounded by sinusoids. Biliary ductule structures, which resemble the ductal plates transiently appearing in mammalian liver development, were observed around the portal veins, but they did not appear around central veins. Thus, the hagfish liver demonstrates the same basic structure as the mammalian liver; that is, a vascular system from portal to central veins via sinusoids, and portal triad structures consisting of portal veins, hepatic arteries, and intrahepatic bile ducts. The epithelial cells of the ductal platelike structures strongly expressed cytokeratin, had some lectin-binding sites, and were delineated by the basal lamina, which was reactive for periodic acid-Schiff (PAS) staining and Iectin histochemistry. The lumina of the ductal plate-like structures were comparatively small and heterogeneous in diameter around the portal veins, suggesting that the biliary structures may not be efficient for bile secretion. The epithelial cells of the gall bladder had a simple columnar shape and were a PAS-positive cytoplasm. Those of bile ducts near the hilus, including extrahepatic and hepatic ducts, were simple columnar or cuboidal cells, and had large lumina. The cytoplasm in these cells was PAS-positive. These phenotypes with the expression of lectin-binding sites were clearly different from those of the ductal plate-like structures in the liver proper, suggesting that the extrahepatic and intrahepatic biliary structures may have different developmental origins. PMID- 22775255 TI - A special construction of subepidermal capillary loops in the hippopotamus (Hippopotamus amphibius). AB - Based on LM, TEM, and histochemical methods, the study describes the specific structure of subepidemal capillary loops in the integument of the hippopotamus (Hippopotamus amphibius). At 25- 60 um, the diameter of the capillaries was more than twenty times larger than those found in other mammals, as was the diameter of the epidermal contact area of the hairpin turn, which had enlarged up to 200 400 um(2). At about 13,400, the number of loops per cm(2) was three times higher than in the few other mammalian species measured to date. The remarkable sheath (thickness 2- 20 um) of the capillary loops consists of a multitude of fine collagen IV fibres, which were in direct contact with the epidermal stratum (str.) basale, emphasizing an origin from the lamina fibroreticularis of the basement membrane. Additionally, the sheath contained many regions filled with free fatty acids. All observations confirmed the view that the walls of the subepidermal capillaries in the hippopotamus are adapted to withstand high blood pressure, permitting a high rate of blood vesselbased heat transfer from the periphery of the body. Until now this function is only known as an important thermoregulatory response in highly active mammals, e.g. dolphins. However, under hot climatic conditions but without strong exercise for cooling, such ability could be an effective and energy-saving procedure in semi-aquatic mammals. PMID- 22775256 TI - External morphology of adult Libythea celtis (Laicharting [1782]) (Lepidoptera: Nymphalidae). AB - Libytheinae is a morphologically unusual group of butterflies whose external anatomy has never been described in detail. The subfamily is considered basal within the diverse family Nymphalidae, and libytheines retain many plesiomorphic features, such as a functional female foreleg and smooth larva. In this paper, we describe and illustrate the adult morphology of Libythea celtis Laicharting, make comparisons to other nymphalid subfamilies, and homologize terms whenever possible. We describe major sclerites, sulci, and the presence of cranial and lateral pits on the tibia, the latter which appear to be previously unreported from the lepidopteran literature. When present, sexual dimorphism and geographic variation are noted. It is hoped that the present paper will help stabilize inconsistencies in morphological terms in nymphalid butterflies. PMID- 22775257 TI - Coalescence theory in livestock breeding. PMID- 22775258 TI - Estimation of historical effective population size using linkage disequilibria with marker data. AB - Theory hypothesizes that the rate of decline in linkage disequilibrium (LD) as a function of distance between markers, measured by r(2), can be used to estimate effective population size (N(e)) and how it varies over time. The development of high-density genotyping makes feasible the application of this theory and has provided an impetus to improve predictions. This study considers the impact of several developments on the estimation of N(e) using both simulated and equine high-density single-nucleotide polymorphism data, when N(e) is assumed to be constant a priori and when it is not. In all models, estimates of N(e) were highly sensitive to thresholds imposed upon minor allele frequency (MAF) and to a priori assumptions on the expected r(2) for adjacent markers. Where constant N(e) was assumed a priori, then estimates with the lowest mean square error were obtained with MAF thresholds between 0.05 and 0.10, adjustment of r(2) for finite sample size, estimation of a [the limit for r(2) as recombination frequency (c) approaches 0] and relating N(e) to c (1 - c/2). The findings for predicting N(e) from models allowing variable N(e) were much less clear, apart from the desirability of correcting for finite sample size, and the lack of consistency in estimating recent N(e) (<7 generations) where estimates use data with large c. The theoretical conflicts over how estimation should proceed and uncertainty over where predictions might be expected to fit well suggest that the estimation of N(e) when it varies be carried out with extreme caution. PMID- 22775259 TI - Founder and present maternal diversity in two endangered Spanish horse breeds assessed via pedigree and mitochondrial DNA information. AB - Pedigree information and 179 mtDNA sequences from two endangered Spanish horse breeds, the Asturcon pony (143) and the Mallorqui horse (36), were analysed to asses: (i) the pedigree and molecular maternal genetic diversity of the two breeds; (ii) the concordance between the dam lines recorded in the corresponding studbooks and the mtDNA haplotypes identified; and (iii) to assess the losses of maternal genetic variability occurred from the foundation of the studbooks to present. Up to 50 Asturcon and 18 Mallorqui founder dam lines were identified in the studbooks analysed. Up to 315 Asturcon mares and 51 Mallorqui mares that foaled in the last 5 years of recording formed a reference population. Only 35 Asturcon and 13 Mallorqui founder dam lines were represented in their reference populations. Sequences from a total of 38 Asturcon and 12 Mallorqui dam lines could be obtained. The 179 sequences obtained gave 15 different haplotypes, 11 and 9 of them being identified, respectively, in the Asturcon pony and in the Mallorqui horse. Five different haplotypes (roughly two-thirds of the sequences) were shared by the two horse breeds. Most dam lines analysed had a single mtDNA haplotype. However, more than one haplotype was detected within eight of the dam lines in Asturcon pony. The found inconsistencies are likely to result from deficiencies in genebank management. The maternal N(e) (mN(e)) computed using the dam line information was higher in the Asturcon pony (20.5) than in the Mallorqui horse (15.9), while these figures were on the opposite direction for the haplotypic line information (6.4 and 9.4, respectively). The ratio of the computed mN(e) values to the actual number of founder dam lines were always higher in the Mallorqui horse probably due to a more balanced distribution of individuals kept for reproduction among studs. Consequences for the conservation programmes of the analysed breeds are discussed. PMID- 22775260 TI - Genetic parameters for energy balance, fat /protein ratio, body condition score and disease traits in German Holstein cows. AB - Various health problems in dairy cows have been related to the magnitude and duration of the energy deficit post partum. Energy balance indicator traits like fat/protein ratio in milk and body condition score could be used in selection programmes to help predicting breeding values for health traits, but currently there is a lack of appropriate genetic parameters. Therefore, genetic correlations among energy balance, fat/protein ratio, and body condition score, and mastitis, claw and leg diseases, and metabolic disorders were estimated using linear and threshold models on data from 1693 primiparous cows recorded within the first 180 days in milk. Average daily energy balance, milk fat/protein ratio and body condition score were 8 MJ NEL, 1.13 and 2.94, respectively. Disease frequencies (% cows with at least one case) were 24.6% for mastitis, 9.7% for metabolic disorders and 28.2% for claw and leg diseases. Heritability estimates were 0.06, 0.30 and 0.34 for energy balance, fat/protein ratio and body condition score, respectively. For the disease traits, heritabilities ranged between 0.04 and 0.15. The genetic correlations were, in general, associated with large standard errors, but, although not significant, the results suggest that an improvement of overall health can be expected if energy balance traits are included into future breeding programmes. A low fat/protein ratio might serve as an indicator for metabolic stability and health of claw and legs. Between body condition and mastitis, a significant negative correlation of -0.40 was estimated. The study provides a new insight into the role energy balance traits can play as auxiliary traits for robustness of dairy cows. It was concluded that both, fat/protein ratio and body condition score, are potential variables to describe how well cows can adapt to the challenge of early lactation. However, the genetic parameters should be re-estimated on a more comprehensive data set. PMID- 22775261 TI - The relationship between feed intake behaviour with intramuscular fat, cholesterol and fatty acid composition in pork. AB - The aim of this study was to investigate the phenotypic relationship between feed intake (FI) characteristics with intramuscular fat, cholesterol and fatty acid composition in pork. Data were available on 202 Duroc barrows. Intramuscular fatness was positively correlated with a higher percentage of saturated (SFA) and monounsaturated fatty acids (MUFA), a lower percentage of polyunsaturated (PUFA), omega-3 (omega3) and omega-6 (omega6) fatty acids, and a lower omega6/omega3 and P:S ratio (p < 0.05). Faster growth resulted in a higher level of SFA and a lower level of omega3 fatty acids (p < 0.05). Increased FI, residual feed intake (RFI) and feed intake time (TIME) and a decreased feed intake frequency (FREQ) resulted in an increase in MUFA, a decrease in PUFA, omega3 and omega6 fatty acids and a lower P:S ratio (p < 0.05). In addition, increased FI and RFI and a decreased FREQ resulted in an increase in SFA (p < 0.05). Most of the correlations were a result of a concomitant relationship with intramuscular fatness and disappeared after correction for that trait. Serum total, high-density lipoprotein and low density lipoprotein cholesterol levels were positively correlated with SFA and MUFA, and negatively with PUFA, omega-3 and omega-6 fatty acids, and the P:S ratio (p < 0.05). These results have implications for programmes aimed at improving meat quality through selection. PMID- 22775262 TI - Genetic correlation between growth and female and male contributions to fertility in rabbit. AB - A Bayesian bivariate Linear-Threshold Animal Model was implemented to determine the genetic correlation between fertility (F), defined as success or failure to conceive, and average daily gain (ADG) in a rabbit line selected for ADG. A total of 27 234 records of F from 7895 females and 1293 males, and 114 135 records of ADG were used for the analysis. The pedigree included 114 485 animals. The model used for ADG included the systematic effects of year-season, parity order and number of kids born alive, the animal additive effect, the maternal and paternal permanent environmental effects, the common litter permanent environmental effect and the residual. The model for the liability of F included the systematic effects of year-season and physiological status of the female, the female and male additive genetic effects, the female and male permanent environmental effects and the residual, which was divided into a permanent environmental effect related to the common litter effect for ADG, and an independent term. The estimated heritabilities were 0.15 for ADG and 0.07 and 0.04 for the female and male contributions to F, respectively. Male and female contributions to F had a positive genetic correlation (0.34). The genetic correlation between ADG and the female component of F was low to moderate and negative (-0.31), whereas it was null for the male contribution to F. Thus, it is expected that only the female contribution to reproductive performance may be impaired by selection for ADG in rabbit lines. PMID- 22775263 TI - Genetic variation of adaptation to heat stress in two Spanish dairy goat breeds. AB - Monthly test-day records of milk yield and composition in Murciano-Granadina (MG) and Payoya (PYA) dairy goats were combined with weather data from meteorological stations, to analyse the effects of heat stress on dairy traits, measured with an index of temperature and relative humidity (THI). A 'repeatability animal model' and a 'reaction norm animal model' were used to estimate genetic (co)variance components. Estimates obtained with both models were very similar. The h(2) of daily yields in MG did not vary throughout the THI scale, but the pattern of variation of content traits showed negative trends for increasing THI values. In PYA, a slight positive tendency throughout the THI scale was observed for the same traits. The genetic correlations between subsequent points in the THI scale were lower than 0.80 when they were computed between low and high THI points. The same reaction norm was observed for all traits. Using the 'reaction norm animal model', it was possible to identify those animals that show the same performance throughout the THI trajectory (robust) and those with varying performances (tolerant and non-tolerant to heat stress). Results in this study also show that heat tolerance decreases, while the genetic level for milk traits increases. Losses because of heat stress were equivalent to 1.9 and 3.1% in the yearly yield of fat and protein for MG and PYA, respectively. PMID- 22775264 TI - Towards candidate genes affecting body fatness at the SSC7 QTL by expression analyses. AB - A quantitative trait locus (QTL) affecting fatness in a way opposite to expectations based on breed means was mapped to swine chromosome 7 (SSC7) using crosses between Large White (LW) and Meishan (MS) founders. Defining the molecular fatness trait more explicitly would allow deducing positional candidate genes, for which expression differences must be analysed in experimental populations. First, mRNA levels of genes representing sequential steps in adipogenesis or involved in lipid metabolism were studied in backfat of pigs having homozygous LW(QTL7)/LW(QTL7) or heterozygous LW(QTL7)/MS(QTL7) alleles and considered at two ages. mRNA level of DLK1 expressed in preadipocytes was greater in MS(QTL7)/LW(QTL7) pigs than in homozygous pigs at 28 days. Transcript abundances of CEBPA involved in differentiation, the prolipogenic FASN gene and the adipocyte-specific marker FABP4 were lower in MS(QTL7)/LW(QTL7) pigs compared with LW(QTL7)/LW(QTL7) pigs at 150 days. Because these results suggest a lag time in terminal differentiation associated with the MS allele, seven genes in the QTL interval were deduced as promising candidates for the QTL effect by bioinformatics analysis. Among them, PPARD and CDKN1A had lower expression levels in MS(QTL7)/LW(QTL7) pigs at both ages. Genotype-related differences were observed in mRNA levels of PPARD target genes involved in cell differentiation (FZD7) or fatty acid oxidation (ACADL and ACOX1) at 150 days. These results re evaluate the potential of PPARD to explain part of variation in pig adiposity. PMID- 22775265 TI - Molecular characterization of the porcine TEAD3 (TEF-5) gene: examination of a promoter mutation as the causal mutation of a quantitative trait loci affecting the androstenone level in boar fat. AB - A quantitative trait loci (QTL) for accumulation of androstenone in fat has been identified in an Large White * Meishan cross in a region of SSC7-containing TEAD3. In humans, TEAD3 is a transcription activator, known to be able to regulate the transcription of HSD3B. This enzyme is involved in the degradation of androstenone in the liver. In this study, porcine transcripts of TEAD3 were characterized and compared with mammalian transcripts. The complete structure of porcine TEAD3 gene was characterized including two 5' non-coding exons and one exon 5 not used in porcine transcripts. Variations were screened in sequences related to TEAD3: in exons, in flanking sequences of exons and in the promoter region. A SNP characterized at 726 bp at 5' of the first exon was tested on several pig populations without coherent and convincing results concerning its association with androstenone levels. We showed that in the liver of adult boars, the transcripts levels of TEAD3 and HSD3B were correlated. As in humans, it is possible that HSD3B is a target gene of TEAD3 in porcine liver. Nevertheless, no expression variation was observed for TEAD3 or HSD3B in liver between animals with different genotypes at the SNP. We concluded that this SNP was not the causal mutation of this QTL. PMID- 22775266 TI - QTL detection from regression analysis of 'generalized de-regressed proof' information. AB - QTL detection using the regression of phenotypes on transmission probability is largely used when large families are available. In three generations designs, the use of a 'de-regressed proof' as a phenotype to be analysed was proposed by Weller et al. (1990) and Tribout et al. (2008). Our work generalizes this approach. A score (that we define as a 'generalized de-regressed proof') is described, which combines performance phenotypes recorded in multigenerational offspring of genotyped individuals. Estimation of the QTL effect on this score with a simple regression is unbiased. The link between this score and the BLUP animal model of the polygenic effect is demonstrated. The theory is developed and two simple examples illustrate how this technique can be implemented. PMID- 22775267 TI - Use of mind-body complementary therapies (MBCTs) in patients with cancer. PMID- 22775268 TI - Directionality of inter- and intramolecular OHO hydrogen bonds: DFT study followed by AIM and NBO analysis. AB - The directionality of inter- and intramolecular OHO hydrogen bonds has been compared. For intramolecular bridges it is determined by an orbital formed in the proton transfer process. For intermolecular bonds, the hydrogen-bonded proton is attached to two lone pairs of the acceptor and the OHO angle is not fixed but can change in a broad range. Depending on the OHO angle, the interaction changes continuously from electrostatic interaction to strong OHO hydrogen bond. PMID- 22775269 TI - Outside case review of surgical pathology for referred patients: the impact on patient care. AB - CONTEXT: Original surgical pathology materials from external sources are reviewed by our pathologists for referred patients before their clinical evaluation and treatment. OBJECTIVE: To identify the rate of major disagreements with diagnoses from external institutions and to characterize the nature and impact of discordant diagnoses on patient care. DESIGN: We identified and reviewed all surgical pathology cases, except for medical liver, medical renal, and cardiac pathology cases, for the period between January 1, 2005, and December 31, 2010, to determine the overall frequency of major disagreements, defined as any change in diagnosis having a substantial impact on patient management. RESULTS: Our review of 71 811 cases initially examined between 2005 and 2010 identified 457 major disagreements (0.6%). The most frequent areas of disagreement were gastrointestinal (80 cases; 17.5%), lymph node (73; 16.0%), bone/soft tissue (47; 10.3%), and genitourinary (43; 9.4%). For a subset of 166 cases reviewed between July 1, 2009, and December 31, 2010, follow-up data were available for 140 (84.3%). Treatment was affected by a changed diagnosis in 126 cases (90.0%), and prognosis was affected in 129 cases (92.1%). For 86 (51.8%) of the 166 cases, additional tissue was obtained. Revised diagnoses concurred with follow-up tissue diagnosis in 84.9% (73 cases), whereas they differed from follow-up tissue diagnosis in 15.1% (13 cases). CONCLUSIONS: Our findings demonstrate the value of outside case review of pathology materials for referred patients, and suggest that it decreases the likelihood of diagnostic errors and provides better protection for patients. PMID- 22775270 TI - Determination of work function of graphene under a metal electrode and its role in contact resistance. AB - Although the work function of graphene under a given metal electrode is critical information for the realization of high-performance graphene-based electronic devices, relatively little relevant research has been carried out to date. In this work, the work function values of graphene under various metals are accurately measured for the first time through a detailed analysis of the capacitance-voltage (C-V) characteristics of a metal-graphene-oxide-semiconductor (MGOS) capacitor structure. In contrast to the high work function of exposed graphene of 4.89-5.16 eV, the work function of graphene under a metal electrode varies depending on the metal species. With a Cr/Au or Ni contact, the work function of graphene is pinned to that of the contacted metal, whereas with a Pd or Au contact the work function assumes a value of ~4.62 eV regardless of the work function of the contact metal. A study of the gate voltage dependence on the contact resistance shows that the latter case provides lower contact resistance. PMID- 22775271 TI - The flame retardant beta-1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane: fate, fertility, and reproductive success in American kestrels (Falco sparverius). AB - Captive American kestrels (Falco sparverius) were exposed via diet during reproduction to an environmentally relevant concentration of beta-1,2-dibromo-4 (1,2-dibromoethyl)cyclohexane (beta-TBECH). The beta-TBECH isomer was injected into the food source at a daily dosing concentration of 0.239 ng/g kestrel/day (22 pairs); control birds were exposed via diet to the safflower oil vehicle only (24 pairs). Eight pairs in each group were exposed for four weeks and sacrificed for tissue analysis; the remaining pairs completed their breeding cycle, with exposure ceasing at the end of incubation (82 days). alpha- and beta-TBECH appeared to be rapidly metabolized and/or eliminated from fat, liver, and plasma; both isomers and potential hydroxylated metabolites of beta-TBECH (plasma) were undetected. Notwithstanding, compared to controls, pairs exposed to beta-TBECH laid fewer eggs (p = 0.019) and laid lighter eggs (successful eggs: p = 0.009). Exposed pairs also demonstrated poorer egg fertility (p = 0.035) although testis mass and histology were similar among males. Reductions in egg production and fertility resulted in decreased hatchling success (p = 0.023). The beta-TBECH exposed pairs also produced fewer males overall (p = 0.009), which occurred concurrently with increased estradiols maternally deposited in eggs (p = 0.039). These findings demonstrate that beta-TBECH may be detrimental for breeding in wild birds receiving similar exposure levels. PMID- 22775272 TI - Influence of heme post-translational modification and distal ligation on the backbone dynamics of a monomeric hemoglobin. AB - The cyanobacterium Synechococcus sp. PCC 7002 uses a hemoglobin of the truncated lineage (GlbN) in the detoxification of reactive species generated in the assimilation of nitrate. In view of a sensing or enzymatic role, several states of GlbN are of interest with respect to its structure-activity relationship. Nuclear magnetic resonance spectroscopy was applied to compare the structure and backbone dynamics of six GlbN forms differing in their oxidation state [Fe(II) or Fe(III)], distal ligand to the iron (histidine, carbon monoxide, or cyanide), or heme post-translational modification (b heme or covalently attached heme). Structural properties were assessed with pseudocontact shift calculations. (15)N relaxation data were analyzed by reduced spectral density mapping (picosecond to nanosecond motions) and by inspection of elevated R(2) values (microsecond to millisecond motions). On the picosecond to nanosecond time scale, GlbN exhibited little flexibility and was unresponsive to the differences among the various forms. Regions of slightly higher mobility were the CE turn, the EF loop, and the H-H' kink. In contrast, fluctuations on the microsecond to millisecond time scale depended on the form. Cyanide binding to the ferric state did not enhance motions, whereas reduction to the ferrous bis-histidine state resulted in elevated R(2) values for several amides. This response was attributed, at least in part, to a weakening of the distal histidine coordination. Carbon monoxide binding quenched some of these fluctuations. The results emphasized the role of the distal ligand in dictating backbone flexibility and illustrated the multiple ways in which motions are controlled by the hemoglobin fold. PMID- 22775273 TI - Computer use among patients with age-related macular degeneration. AB - PURPOSE: Age-related macular degeneration (AMD) is the leading cause of incurable vision loss in older adults in industrialized countries and is on a trajectory to disable a growing number of persons as societies age. To assess the potential of using telemedicine for expansion of an in-person AMD self-management program, we examined the extent of computer use in a sample of older adults with AMD. METHODS: 160 older adult volunteers (mean age = 76 years; female = 51%) with AMD (mean visual acuity in better eye: 20/40; worse eye: 20/90) were randomly selected from members of the San Diego County AMD Registry. Computer use was assessed with a Health and Impact Questionnaire. Dependent measures were Snellen visual acuity, National Eye Institute-Visual Function Questionnaire, the AMD Self Efficacy Questionnaire, and the Geriatric Depression Scale. RESULTS: Overall 70.6% reported computer use at least once per month. By age and gender stratum, 76.5% of men aged 60-74 years, 73.3% of men aged 75 years and over, 74.3% of women aged 60-74 years, and 60.9% of women aged 75 years and over used computers. In logistic regression analyses controlling for age and gender, computer use was associated with better visual acuity (P = 0.029), higher education (P = 0.002), and self-efficacy for communication (P = 0.027). CONCLUSION: The majority of older adults with AMD in our sample used computers, with use highest among more educated and visually intact patients. Computer use to access the Internet is feasible in AMD patients and should be encouraged. The inclusion of computer use in measures of AMD-related functioning appears warranted. PMID- 22775274 TI - Relationship between retinopathy severity, visual impairment and depression in persons with long-term type 1 diabetes. AB - PURPOSE: Our aim was to investigate the proportion of individuals with depression and its association with diabetic retinopathy and visual impairment in a cohort with 25 or more years of type 1 diabetes. METHODS: This was a cross-sectional analysis at the 25-year follow-up of the population-based cohort of the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Examinations followed standardized protocols and included clinical and ophthalmic evaluations and questionnaires to assess current and past medical history, use of medications, and cigarette smoking. The Center for Epidemiologic Studies Depression Scale (CES-D) was administered to all participants. Depression was defined as use of antidepressant or CES-D score >=16. RESULTS: A total of 484 individuals were included in the analysis. The proportion of depression was 37.8% (95% confidence interval 33.4 42.3%). A higher proportion of individuals with depression was observed among those with more severe diabetic retinopathy and visual impairment. However these associations were not statistically significant while controlling for other factors in the multivariable analyses. CONCLUSIONS: Diabetic retinopathy severity and visual acuity in persons with long duration of type 1 diabetes were not cross sectionally associated with depression in this cohort. PMID- 22775275 TI - Onchocerciasis as a risk factor for night blindness. AB - PURPOSE: In the Kaduna State Nigeria Onchocerciasis focus, the prevalence of reported night blindness (RNB) was 12.9%, higher than the national average (1%), and a control non-onchocercal community (0.83%, P < 0.0001). Risk factors for RNB were explored. METHODS: This was an analysis of baseline data from the phase three ivermectin trials in Kaduna (1988-1995). 6831 subjects in the onchocercal zone and 1563 in the control zone were examined. Ordinal logistic regression was used to assess the relationship between microfilaria load (uninfected, low (<10 mf/mg), moderate (10-49 mf/mg) and high (50+ mf/mg)) and likelihood of RNB. RESULTS: Ocular evidence of vitamin A deficiency (Bitot spots or xerophthalmia) was absent in both populations. The excess risk of nightblindness attributable to domicile in this onchocerciasis-endemic area was 11.9% with a population attributable fraction of 92.2%. The prevalence of RNB and age-adjusted odds ratio increased with higher microfilaria load (P < 0.0027.) Subjects with onchocerciasis-related ocular lesions such as optic nerve disease (OND; age adjusted OR 2.29, 95% confidence interval, CI, 1.86-2.83), sclerosing keratitis (OR 2.75, 95% CI 2.10-3.50), and onchocercal chorioretinitis (OR 1.66, 95% CI 1.22-2.26) were significantly more likely to report night blindness. Overall, subjects with a primary diagnosis of 'ocular onchocerciasis' were 50% more likely to report night blindness. OND, cataract and trachoma together accounted for 52% of all RNB but OND (onchocerciasis-related in 80% of cases) emerged as the single most common associated pathology in 30% of cases. CONCLUSIONS: Onchocercal infection probably accounted for the excess of RNB in this focus. PMID- 22775276 TI - Rapid assessment of avoidable blindness in two northern provinces of Burundi without eye services. AB - PURPOSE: To determine the prevalence and causes of blindness, severe visual impairment and visual impairment as well as cataract surgical coverage in two northern provinces of Burundi for the purpose of planning eye services. METHODS: The population-based Rapid Assessment of Avoidable Blindness survey methodology was used. RESULTS: Of 3800 people enrolled, 3684 (97%) were examined. The sample prevalences of blindness, severe visual impairment, and visual impairment were 1.1% (95% confidence interval, CI 0.8-1.4), 0.6% (95% CI 0.4-0.9), and 1.7% (95% CI 1.3-2.1), respectively. The leading causes of blindness were cataract (55%) and posterior segment causes (37%). Severe visual impairment was mainly due to cataract (43%) and refractive error (39%), and visual impairment was mainly due to refractive error (67%) and cataract (18%). Cataract surgical coverage by person at the level of <6/60 was 15%. CONCLUSIONS: The low prevalence of vision loss in this area with no eye services and a low cataract surgical coverage rate is surprising and possibly due to the effects of the previous years of conflict in which those with decreased vision may have been most likely to perish. If this explanation is correct, then Burundi needs to plan to deal with a markedly increasing prevalence of cataract in future. PMID- 22775277 TI - Trachoma prevalence in women living in rural northern India: rapid assessment findings. AB - PURPOSE: Rapid assessment of cicatricial trachoma in adult females aged over 15 years in a previously hyperendemic rural area in Haryana, North India. METHODS: Ten disadvantaged villages each with a population of 3000-5000 were chosen by cluster random sampling. One thousand females, 500 between 15-30 years and the rest over 30 years in the underdeveloped parts of the villages, identified by observation and consultation, were examined for signs of trachomatous scarring (TS), trachomatous trichiasis (TT) and trachomatous corneal opacity (TCO). Examinations of both eyes were performed with the aid of a binocular loupe (2.5x magnification) for signs of trachoma, its complications and other ocular morbidities. RESULTS: Bilateral examination was carried out in all participants. About two-thirds (n = 650; 65%) of subjects did not have any signs of trachoma. The percentages of trachoma stages TS, TT and TCO were found to be 26.4%, 5.4% and 3.2% respectively. Trichiasis was observed in 54 subjects, all in the age group >30 years, and highest in the age group 66-75 years (22.8%). Females in the age group >30 years had significantly higher cicatricial trachoma compared to females <30 years (p < 0.001). Overall 59.3% of affected females had not received any treatment. Epilation and entropion surgery had been performed in 30.3% and 10.4% of affected females, respectively. CONCLUSION: The results of our rapid assessment suggest that the presence of cicatricial trachoma remains an important health issue in females over 15 years of age. PMID- 22775278 TI - Acanthamoeba keratitis: the persistence of cases following a multistate outbreak. AB - PURPOSE: To describe the trend of Acanthamoeba keratitis case reports following an outbreak and the recall of a multipurpose contact lens disinfection solution. Acanthamoeba keratitis is a serious eye infection caused by the free-living amoeba Acanthamoeba that primarily affects contact lens users. METHODS: A convenience sample of 13 ophthalmology centers and laboratories in the USA, provided annual numbers of Acanthamoeba keratitis cases diagnosed between 1999 2009 and monthly numbers of cases diagnosed between 2007-2009. Data on ophthalmic preparations of anti-Acanthamoeba therapies were collected from a national compounding pharmacy. RESULTS: Data from sentinel site ophthalmology centers and laboratories revealed that the yearly number of cases gradually increased from 22 in 1999 to 43 in 2003, with a marked increase beginning in 2004 (93 cases) that continued through 2007 (170 cases; p < 0.0001). The outbreak identified from these sentinel sites resulted in the recall of a contact lens disinfecting solution. There was a statistically significant (p <= 0.0001) decrease in monthly cases reported from 28 cases in June 2007 (following the recall) to seven cases in June 2008, followed by an increase (p = 0.0004) in reported cases thereafter; cases have remained higher than pre-outbreak levels. A similar trend was seen in prescriptions for Acanthamoeba keratitis chemotherapy. Cases were significantly more likely to be reported during summer than during other seasons. CONCLUSION: The persistently elevated number of reported cases supports the need to understand the risk factors and environmental exposures associated with Acanthamoeba keratitis. Further prevention efforts are needed to reduce the number of cases occurring among contact lens wearers. PMID- 22775279 TI - Spectacle dispensing in Timor-Leste: tiered-pricing, cross-subsidization and financial viability. AB - PURPOSE: To examine the financial viability of the Timor-Leste National Spectacle Program as it increases spectacle availability, affordability and uptake, particularly for Timor's poor. METHODS: In rural areas, three models of ready made spectacles were dispensed according to a tiered pricing structure of US$3.00, 1.00, 0.10 and 0.00. In addition, custom-made spectacles were available in the capital, Dili. Spectacle costs, dispensing data and income for the National Spectacle Program for 18 months from March 2007 were analyzed. RESULTS: Rural services dispensed 3415 readymade spectacles: 47.1% to women, and 51.4% at subsidized prices, being 39.8% at US$0.10 and 11.6% free. A profit of US$1,529 was generated, mainly from the sale of US$3.00 spectacles. Women (odds ratio, OR, 1.3, 95% confidence interval, CI, 1.1-1.4) and consumers aged >=65 years (OR 2.1; 95% CI 1.7-2.6) were more likely to receive subsidized spectacles. Urban services dispensed 2768 spectacles; mostly US$3.00 readymade (52.8%) and custom-made single vision (29.6%) units. Custom-made spectacles accounted for 36.7% of dispensing, but 73.1% of the US$12,264 urban profit. The combined rural and urban profit covered all rural costs, leaving US$2,200 to meet administration and other urban expenses. CONCLUSION: It is instructive and encouraging that a national spectacle dispensing program in one of the ten poorest countries of the world can use tiered-pricing based on willingness-to-pay information to cover spectacle stock replacement costs and produce profit, while using cross-subsidization to provide spectacles to the poor. PMID- 22775280 TI - Self-medication in ophthalmology: a questionnaire-based study in an Argentinean population. AB - PURPOSE: The aim of this study was to identify practices of self-medication in the treatment of ocular conditions and to identify a profile of patients who self medicate. METHODS: We conducted a cross-sectional descriptive survey of patients, over the age of 17 years seen in our ophthalmology practice in Cordoba, Argentina. Self-medication was defined as the use of ophthalmic medicines which had not been prescribed by a health care specialist in the previous year. RESULTS: The sample included 379 subjects, 162 males (43%) and 217 females (57%); mean age 46.8 years. Prior to looking for medical attention in our institution, 97 patients (25.6%) reported self-medicating. The most frequently employed products included non-steroidal anti-inflammatory drops in combination with a vasoconstrictive agent (32%) followed by a combination of antibiotics and steroids (9%), however, 14% of patients did not remember the name or type of medication applied. A total of 31% of patients used drugs recommended by a pharmacist; 25% used drugs of their own choosing and 24% followed suggestions from a friend or family member. Only 12% of patients knew the drug's components and only 3% were aware of any possible side effects. There was no difference in behavior patterns related to educational level or age, however, there was a significant difference related to gender, with males misusing ophthalmic drops more frequently than women (P = 0.004). CONCLUSIONS: Patients commonly attempt to treat conditions that require ophthalmologic care by self-medicating with over the-counter eye drops. Educational efforts to inform patients of the consequences of self-medication are necessary. PMID- 22775282 TI - Optic nerve complex imaging in glaucoma Medicare beneficiaries. AB - PURPOSE: To assess the frequency of fundus photography and scanning computerized ophthalmic diagnostic imaging (SCODI) on patients receiving glaucoma care under Medicare. METHODS: In this retrospective, observational, Medicare claims-based study, we used a 5% random sample, from 2006-2008, of Medicare beneficiaries, selected for International Classification of Diseases, 9th Revision (ICD-9) diagnoses of glaucoma or glaucoma suspect, who had greater than one year of follow up (N = 143,374). The proportion of patients with an ICD-9 diagnosis of glaucoma or glaucoma suspect who received fundus photography (Physicians' Current Procedural Terminology, CPT 99250) or scanning computerized ophthalmic diagnostic imaging (SCODI; CPT 92135) was determined. RESULTS: A total of 48% of patients did not have any form of imaging during the study period. Among those who were imaged, 27% were imaged only once. The use of fundus photography was significantly lower than the use of SCODI (p < 0.00005). A total of 75% of those imaged once received SCODI while only 25% were photographed. Analysis of optic nerve complex imaging over time revealed that 20% received SCODI and 6% were photographed in the first quarter of appearance of the glaucoma or suspect diagnosis code in the dataset, with a decline thereafter. CONCLUSIONS: Optic disc imaging in patients diagnosed with glaucoma or glaucoma suspect may not meet guidelines set by the American Academy of Ophthalmology. While both modalities are underused, optic disc photos are performed less often and repeated less frequently when compared to SCODI. Underuse of imaging may negatively impact detection of disease progression over time in glaucoma patients. PMID- 22775281 TI - The role of demographic characteristics in the outcomes of cataract surgery and gender roles in the uptake of postoperative eye care: a hospital-based study. AB - PURPOSE: To explore the effect of demographic characteristics on the outcomes of cataract surgery in terms of visual acuity and patient satisfaction, and gender role in the uptake of postoperative care. METHODS: Comprehensive ocular examinations were performed on 478 subjects (558 eyes) over the age of 50 years who underwent surgery for age-related cataract at the largest eye hospital in Iran. Demographic characteristics were obtained and surgical records were reviewed. RESULTS: Male subjects had significantly better outcomes in terms of uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA) (mean difference 0.12 and 0.13 logMAR; p = 0.004 and p < 0.001, respectively). Women were significantly less satisfied than men (73.2% vs. 83.6%; p = 0.011). Postoperative UCVA and BSCVA were better in patients with higher levels of education (both p < 0.001). Age had an inverse association with UCVA (p = 0.004) and BSCVA (p < 0.001). Women were twice as likely to need capsulotomy (p = 0.002). Men's uptake of postoperative refractive care was 4-fold that of women's (31% vs. 7%). In multivariable analyses, age, sex, education, presence of ocular comorbidity and need for capsulotomy, spectacle prescription and other care were associated with postoperative UCVA (all p < 0.05; adjusted R(2) = 0.256). CONCLUSION: Female patients were shown to be at a clear disadvantage in cataract surgery; outcomes of the procedure and postoperative care were both poorer. Older age, lower level of education, ocular comorbidity and unmet postoperative need were also associated with a poorer outcome. PMID- 22775283 TI - Association of His1085His INSR gene polymorphism with type 2 diabetes in South Indians. AB - BACKGROUND AND OBJECTIVE: The INSR gene, which encodes the insulin receptor, is a candidate gene for type 2 diabetes (T2D). The objective of the present study was to sequence some of the crucial exons in the INSR gene such as exon 2, which encodes the insulin-binding domain of the INSR protein, and exons 17-21, which encode the protein tyrosine kinase domain for mutations/polymorphisms, and to study their association with T2D in the South Indian population. SUBJECTS AND METHODS: The INSR gene was sequenced in 25 normal glucose-tolerant (NGT) and 25 T2D subjects, and the variant found was genotyped by polymerase chain reaction restriction fragment length polymorphism in 1,016 NGT and 1,010 T2D subjects, randomly selected from the Chennai Urban Rural Epidemiology Study. RESULTS: Only one previously reported polymorphism, His1085His [rs1799817, (C->T)], in exon 17 was detected by sequencing. The frequency of the "T" allele of the His1085His polymorphism was significantly lower in the T2D subjects (31%) compared with the NGT subjects (35%) and showed significant protection against diabetes (odds ratio 0.85, 95% confidence interval 0.75-0.97, P=0.019). Regression analysis according to a recessive model taking the CC+CT genotype as the reference showed that the TT genotype was protective against diabetes (odds ratio 0.71, 95% confidence interval 0.50-0.99, P=0.048). Adjusting this P value by the number of competing models (three) using Bonferroni's correction, we found that the association finding did not remain significant. CONCLUSIONS: The "T" allele of the His1085His polymorphism in the INSR gene shows significant protection against diabetes. This study gains importance because there are no data available to date on the role of INSR variants in T2D in the Indian population. PMID- 22775284 TI - Flavonol-containing phosphorylated pullulan may attenuate pulp inflammation. AB - AIM: To find possible reagents to minimize inflammatory responses by using an established pulpitis models for the purpose of developing new pulp-capping materials, and to test the possible use of phosphorylated pullulan as a carrier for such an anti-inflammatory reagent. METHODOLOGY: Co-culturing was performed using transwell systems. Inflammatory responses were evaluated by measuring cytokines produced by the cells. The effects of two flavonoids, luteolin and quercetin, as anti-inflammatory reagents, and phosphorylated pullulan, which potentially achieves a sufficient marginal sealing to hydroxyapatite and slowly releases luteolin, as a carrier for flavonoids, were tested. RESULTS: Flavonols, particularly luteolin, dramatically attenuated inflammatory cytokine production, which was augmented by co-cultures. Luteolin was successfully enclosed by phosphorylated pullulan. Finally, it was confirmed that luteolin released from phosphorylated pullulan was effective in reducing cytokine production by co cultures. CONCLUSIONS: Combination of phosphorylated pullulan and luteolin could be potentially used in the treatment of dental pulp inflammation. PMID- 22775285 TI - Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction. AB - Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie the maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) that was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both the function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. PMID- 22775286 TI - Negative regulation of CCaMK is essential for symbiotic infection. AB - One of the earliest responses of legumes to symbiotic signalling is oscillation of the calcium concentration in the nucleoplasm of root epidermal cells. Integration and decoding of the calcium-spiking signal involve a calcium- and calmodulin-dependent protein kinase (CCaMK) and its phosphorylation substrates, such as CYCLOPS. Here we describe the Lotus japonicus ccamk-14 mutant that originated from a har1-1 suppressor screen. The ccamk-14 mutation causes a serine to asparagine substitution at position 337 located within the calmodulin binding site, which we determined to be an in vitro phosphorylation site in CCaMK. We show that ccamk-14 exerts cell-specific effects on symbiosis. The mutant is characterized by an increased frequency of epidermal infections and significantly compromised cortical infections by Mesorhizobium loti and also the arbuscular mycorrhiza fungus Rhizophagus irregularis. The S337 residue is conserved across angiosperm CCaMKs, and testing discrete substitutions at this site showed that it participates in a negative regulation of CCaMK activity, which is required for the cell-type-specific integration of symbiotic signalling. PMID- 22775287 TI - Periodontitis associated with chronic kidney disease among Mexican Americans. AB - OBJECTIVE: In comparison to non-Hispanic whites, a number of health-care disparities, including poor oral health, have been identified among Hispanics in general and Mexican Americans in particular. We hypothesized that Mexican Americans with chronic kidney disease (CKD) would have higher prevalence of chronic periodontitis compared with Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. METHODS: We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) data set. We followed the American Academy of Periodontology/Center for Disease Control and Prevention case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. RESULTS: Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose response association (P<0.001). Mexican Americans with reduced kidney function were twofold more likely to have periodontitis compared with Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes, and socioeconomic status. Multivariate adjusted odds ratio for periodontitis significantly increased with 1, 5, and 10 mL/minute estimated glomerular filtration rate reduction from the mean. CONCLUSION: This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. PMID- 22775288 TI - Normal vs. disordered bereavement-related depression: are the differences real or tautological? AB - OBJECTIVE: To evaluate whether the DSM distinction between uncomplicated (normal) and complicated (disordered) bereavement-related depression (BRD) has discriminant validity on a range of pathology indicators. The DSM's major depression bereavement exclusion (BE) excludes BRDs from diagnosis when they are uncomplicated (defined by brief duration, non-severe impairment, and lack of certain pathosuggestive symptoms) but classifies all other ("complicated") BRDs as major depression. A previous report seemed to support the uncomplicated/complicated distinction's discriminant validity. However, those arguing for eliminating the BE from DSM-5 dismiss the findings as 'tautological,' attributing the validator differences to definitional biases (e.g. 'uncomplicated' requires 'no suicidal ideation,' yet 'lifetime suicide attempt' was a validator). This study empirically tests whether the uncomplicated/complicated differences are real or tautological. METHOD: Using National Comorbidity Survey data, confounds between definitional criteria for 'uncomplicated' and pathology validators were identified and corrected by deleting the biasing criteria and recalculating the corresponding validator's outcome. RESULTS: Six validators (interference with life, suicide attempt, melancholic depression, duration, hospitalization, and number of symptoms) were reanalyzed using unbiased definitions for 'uncomplicated.' All still yielded significantly lower pathology levels for uncomplicated BRDs, disconfirming the 'tautology' hypothesis. Regression analysis revealed that 'uncomplicated' offered incremental validity over severity alone in predicting pathology, so 'uncomplicated' cannot be equated with 'mild.' CONCLUSION: Uncomplicated BRDs' lower pathology validator levels are because of real syndromal differences, not definitional tautologies, supporting the BE's validity. PMID- 22775289 TI - The neural signatures of distinct psychopathic traits. AB - Recent studies suggest that psychopathy may be associated with dysfunction in the neural circuitry supporting both threat- and reward-related processes. However, these studies have involved small samples and often focused on extreme groups. Thus, it is unclear to what extent current findings may generalize to psychopathic traits in the general population. Furthermore, no studies have systematically and simultaneously assessed associations between distinct psychopathy facets and both threat- and reward-related brain function in the same sample of participants. Here, we examined the relationship between threat-related amygdala reactivity and reward-related ventral striatum (VS) reactivity and variation in four facets of self-reported psychopathy in a sample of 200 young adults. Path models indicated that amygdala reactivity to fearful facial expressions is negatively associated with the interpersonal facet of psychopathy, whereas amygdala reactivity to angry facial expressions is positively associated with the lifestyle facet. Furthermore, these models revealed that differential VS reactivity to positive versus negative feedback is negatively associated with the lifestyle facet. There was suggestive evidence for gender-specific patterns of association between brain function and psychopathy facets. Our findings are the first to document differential associations between both threat- and reward related neural processes and distinct facets of psychopathy and thus provide a more comprehensive picture of the pattern of neural vulnerabilities that may predispose to maladaptive outcomes associated with psychopathy. PMID- 22775290 TI - Concordance of outcomes of pairs of kidneys transplanted into different recipients. AB - Kidney transplant outcomes are influenced by donor characteristics, including age and gender. Additional donor factors, both genetic and environmental, also influence graft outcome. We aim to assess the strength of donor factors in determining kidney transplant outcomes by comparing paired kidneys from a single donor transplanted into different recipients. We conducted a retrospective cohort study of outcomes of pairs of deceased donor kidneys transplanted in our centre between 1992 and 2008. We examined the relationship within pairs for eGFR at 1 year and at 5 years post-transplant using Spearman's Correlation and the concordance of pairs of transplant kidneys with respect to the occurrence of acute rejection and delayed graft function (DGF). A total of 652 recipient pairs were analysed. Spearman's correlation for eGFR was 0.36 at 1 year and 0.36 at 5 years post-transplant. The incidence of DGF was 11%. The odds ratio of DGF occurring if the contralateral kidney had DGF was 5.99 (95% CI, 3.19-11.25). There is a significant degree of relationship within pairs of kidneys transplanted from the same donor for serum creatinine at 1 year and 5 years post transplant and also for the occurrence of delayed graft function. PMID- 22775292 TI - Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. AB - Melatonin is a synchronizer of many physiological processes. Abnormal melatonin signaling is associated with human disorders related to sleep, metabolism, and neurodevelopment. Here, we present the X-ray crystal structure of human N-acetyl serotonin methyltransferase (ASMT), the last enzyme of the melatonin biosynthesis pathway. The polypeptide chain of ASMT consists of a C-terminal domain, which is typical of other SAM-dependent O-methyltransferases, and an N-terminal domain, which intertwines several helices with another monomer to form the physiologically active dimer. Using radioenzymology, we analyzed 20 nonsynonymous variants identified through the 1000 genomes project and in patients with neuropsychiatric disorders. We found that the majority of these mutations reduced or abolished ASMT activity including one relatively frequent polymorphism in the Han Chinese population (N17K, rs17149149). Overall, we estimate that the allelic frequency of ASMT deleterious mutations ranges from 0.66% in Europe to 2.97% in Asia. Mapping of the variants on to the 3-dimensional structure clarifies why some are harmful and provides a structural basis for understanding melatonin deficiency in humans. PMID- 22775291 TI - Prospective effects of traumatic event re-exposure and post-traumatic stress disorder in syringe exchange participants. AB - AIM: Determine the effect of traumatic event re-exposure and post-traumatic stress disorder (PTSD) symptom severity on proximal drug use and drug abuse treatment-seeking in syringe exchange participants. DESIGN: Prospective longitudinal 16-month cohort study of new syringe exchange registrants enrolled in a parent study of methods to improve treatment engagement. SETTING: Data were collected in a research van next to mobile syringe exchange distribution sites in Baltimore, Maryland. PARTICIPANTS: Male and female (n = 162) injecting drug users (IDUs) registered for syringe exchange. MEASUREMENTS: Traumatic event re-exposure was identified each month with the Traumatic Life Events Questionnaire. PTSD symptoms were measured with the Modified PTSD Symptom Scale-Revised, given every 4 months. Outcome measures collected monthly were days of drug use (heroin, cocaine) and drug abuse treatment-seeking behavior (interest, calls to obtain treatment, treatment participation). FINDINGS: Each traumatic event re-exposure was associated with about 1 more day of cocaine use after accounting for the previous month's cocaine use [same month adjusted B, standard error = 1.16 (0.34); 1 month later: 0.99 (0.34)], while PTSD symptoms had no effect. Traumatic event re-exposure increased interest in drug abuse treatment [same month adjusted odds ratios with 95% confidence intervals = 1.34 (1.11-1.63)] and calling to obtain treatment [same month 1.58 (1.24-2.01); 1 month later 1.34 (1.03-1.75)]. Each 10% increase in PTSD symptom severity was associated with persistent increased interest in treatment [same month 1.25 (1.10-1.42); 1 month later 1.16 (1.02-1.32); 2 months later 1.16 (1.02-1.32)] and calling to obtain treatment [same month 1.16 (1.02-1.32)]. Neither traumatic events nor PTSD symptoms were associated with participants receiving treatment. CONCLUSIONS: Becoming exposed again to traumatic events among injecting drug users is associated with an increase in cocaine use up to 1 month later, but drug use is not related to post traumatic stress disorder symptoms. Both traumatic event re-exposure and post traumatic stress disorder symptoms predict drug abuse treatment-seeking behavior for up to 2 months. PMID- 22775293 TI - Periodic DFT study of acidic trace atmospheric gas molecule adsorption on Ca- and Fe-doped MgO(001) surface basic sites. AB - The electronic properties of undoped and Ca- or Fe-doped MgO(001) surfaces, as well as their propensity toward atmospheric acidic gas (CO2, SO2, and NO2) uptake was investigated with an emphasis on gas adsorption on the basic MgO oxygen surface sites, O(surf), using periodic density functional theory (DFT) calculations. Adsorption energy calculations show that MgO doping will provide stronger interactions of the adsorbate with the O(surf) sites than the undoped MgO for a given adsorbate molecule. Charge transfer from the iron atom in Fe doped MgO(001) to NO2 was shown to increase the binding interaction between adsorbate by an order of magnitude, when compared to that of undoped and Ca-doped MgO(001) surfaces. Secondary binding interactions of adsorbate oxygen atoms were observed with surface magnesium sites at distances close to those of the Mg-O bond within the crystal. These interactions may serve as a preliminary step for adsorption and facilitate further adsorbate transformations into other binding configurations. Impacts on global atmospheric chemistry are discussed as these adsorption phenomena can affect atmospheric gas budgets via altered partitioning and retention on mineral aerosol surfaces. PMID- 22775295 TI - Conformation and energy transfer in single conjugated polymers. AB - In contrast to the detailed understanding of inorganic materials, researchers lack a comprehensive view of how the properties of bulk organic materials arise from their individual components. For conjugated polymers to eventually serve as low cost semiconductor layers in electronic devices, researchers need to better understand their functionality. For organics, traditional materials science measurements tend to destroy the species of interest, especially at low concentrations. However, fluorescence continues to be a remarkably flexible, relatively noninvasive tool for probing the properties of individual molecules and allows researchers to carry out a broad range of experiments based on a relatively simple concept. In addition, the sensitivity of single-molecule spectroscopy allows researchers to see the properties of an individual component that would be masked in the bulk phase. In this Account, we examine several photophysical properties of different conjugated polymers using single-molecule spectroscopy. In these experiments, we probed the relationship between the conformation of single conjugated polymer chains and the distance scale and efficiency of energy transfer within the polymer. Recent studies used polarization anisotropy measurements on single polymer chains to study chain folding following spin-casting from solution. This Account summarizes the effects of monomer regioregularity and backbone rigidity, by comparing a regiorandom phenylene vinylene (MEH-PPV) with both a regiorandom and regioregular thiophene (P3HT). Synthesis of novel polymers allowed us to explore the role of different conformation-directing inclusions in a PPV backbone. We showed that these inclusions control the conformation of individual chains and that molecular dynamics can predict these structural effects. In situ solvent vapor annealing studies explored the dynamics of polymer chains as well as the effect of solvent evaporation on the structural equilibrium of the polymer. We observed that a slower rate of solvent evaporation results in a narrow population of highly ordered polymer chains. These highly ordered single chains serve as a model system to probe the effect of conformation on energy transfer following excitation in single MEH-PPV polymer chains in two distinct experiments. In the first, we correlated the anisotropy of the fluorescence emission of individual chains with the anisotropy of their fluorescence excitation. Using this data, we derived a model for energy transfer in a conjugated polymer, simulating chromophores along a chain, coupled via Forster energy transfer. In the second experiment, super-resolution measurements demonstrated the ability of single molecule spectroscopy to directly visualize energy transfer along a polymer chain embedded in a model device environment. A capacitive device allowed for controlled localization of hole polarons onto the polymer chain. These positive charges subsequently quenched local excitations, providing insight into the range of energy transfer in these single polymer molecules. As researchers continue to characterize conjugated polymer films and develop methods for creating multichain systems, single-molecule techniques will provide a greater understanding of how polymer morphology influences interchain interactions and will lead to a richer description of the electronic properties of bulk conjugated polymer films. PMID- 22775296 TI - Evaluation of partial-mouth recording systems of gingival parameters in a Portuguese adult population. AB - OBJECTIVE: To analyze the diagnostic reliability of various partial-mouth recording systems (PMRS) for the simultaneous assessment of supragingival plaque, calculus, and gingival inflammation in a population of Portuguese adults. METHODS: A single examiner determined the levels of plaque, calculus, and gingival inflammation in 108 subjects using quantitative and dichotomous indices. Half-mouth and <= 10-tooth PMRS were compared with full-mouth examination (FME). RESULTS: On comparison with FME, Q1+Q3, Q1+Q4, Q2+Q3, Q2+Q4 combinations and the Ramfjord teeth did not show statistically significant differences in the simultaneous assessment of plaque, calculus, and gingival inflammation using both quantitative and dichotomous indices. Comparison of the prevalence of subjects that presented discrepancy in the three clinical parameters between FME and PMRS, Q1+Q3 combination was associated with lower percentages of discrepancy (range of discrepancies=0.9-6.4 percent) and a higher specificity (>= 0.90) and sensitivity (>= 0.89). CONCLUSIONS: The Q1+Q3 combination could be particularly applicable in studies investigating relationships between the state of gingival health and environmental or patient-related systemic factors, as well as in the development of oral health scales that include gingival parameters. PMID- 22775294 TI - Colorectal cancer screening and physical activity promotion among obese women: an online evaluation of targeted messages. AB - Obese women are at higher risk for several cancers, but are less likely than normal weight women to engage in cancer prevention behaviors such as screening and physical activity. Targeted health messages may help increase healthy behaviors among vulnerable groups such as obese women. Using findings from focus groups with obese women, the authors created targeted messages to promote colorectal cancer screening and physical activity among obese women. The messages addressed psychosocial constructs, such as benefits and barriers to colorectal cancer screening and exercise, which were relevant to the target population. Messages were tested online with women age 50 years and older (N = 181). Participants were stratified by weight (obese vs. nonobese) and randomized to review either 10 targeted (intervention) or 10 generic (control) messages. Study outcomes included elaboration about the messages, message relevance and trustworthiness, and behavioral intentions. The authors used moderation and subgroup analyses to determine whether the intervention messages were better received by certain women. They found no differences in elaboration, behavioral intentions, relevance, or trustworthiness between intervention and control for either weight group. However, exercise intentions increased more (p = .06) among inactive obese women who received intervention messages (+2.9) compared with those who were in the control group (+1.2). Intervention messages also produced more elaboration among women who viewed their weight as a barrier to screening or exercise. Tailoring intervention messages for obese women on the basis of behavior and barriers may improve outcomes more than giving the same messages to all obese women. PMID- 22775297 TI - Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-alpha) pathways. AB - Eugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro-inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3 300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 +/- 10% and 90 +/- 6% of the acetic acid-induced nociception, with ID50 values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3-100 mg/kg, i.p.) reduced the response behavior by 62 +/- 5% with an ID50 of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 +/- 9%), kainic (acid kainite) (41 +/- 12%), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (55 +/- 5%), and substance P (SP) (39 +/- 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF-alpha, 65 +/- 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF-alpha. Thus, eugenol could represent an important compound in the treatment for acute pain. PMID- 22775298 TI - Phenotypic heterogeneity and full penetrance in a family with dopa-responsive dystonia. PMID- 22775299 TI - Flight of a cytidine deaminase complex with an imperfect transition state analogue inhibitor: mass spectrometric evidence for the presence of a trapped water molecule. AB - Cytidine deaminase (CDA) binds the inhibitor zebularine as its 3,4-hydrate (K(d) ~ 10(-12) M), capturing all but ~5.6 kcal/mol of the free energy of binding expected of an ideal transition state analogue (K(tx) ~ 10(-16) M). On the basis of its entropic origin, that shortfall was tentatively ascribed to the trapping of a water molecule in the enzyme-inhibitor complex, as had been observed earlier for product uridine [Snider, M. J., and Wolfenden, R. (2001) Biochemistry 40, 11364-11371]. Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) of CDA nebularized in the presence of saturating 5-fluorozebularine reveals peaks corresponding to the masses of E(2)Zn(2)W(2) (dimeric Zn-CDA with two water molecules), E(2)Zn(2)W(2)Fz, and E(2)Zn(2)W(2)Fz(2), where Fz represents the 3,4 hydrate of 5-fluorozebularine. In the absence of an inhibitor, E(2)Zn(2) is the only dimeric species detected, with no additional water molecules. Experiments conducted in H(2)(18)O indicate that the added mass W represents a trapped water molecule rather than an isobaric ammonium ion. This appears to represent the first identification of an enzyme-bound water molecule at a subunit interface (active site) using FTICR-MS. The presence of a 5-fluoro group appears to retard the decomposition of the inhibitory complex kinetically in the vapor phase, as no additional dimeric complexes (other than E(2)Zn(2)) are observed when zebularine is used in place of 5-fluorozebularine. Substrate competition assays show that in solution zebularine is released from CDA (k(off) > 0.14 s(-1)) much more rapidly than is 5-fluorozebularine (k(off) = 0.014 s(-1)), despite the greater thermodynamic stability of the zebularine complex. PMID- 22775300 TI - The Strauss and Carpenter Prognostic Scale in subjects clinically at high risk of psychosis. AB - OBJECTIVE: To investigate the predictive value of the Strauss and Carpenter Prognostic Scale (SCPS) for transition to a first psychotic episode in subjects clinically at high risk (CHR) of psychosis. METHOD: Two hundred and forty-four CHR subjects participating in the European Prediction of Psychosis Study were assessed with the SCPS, an instrument that has been shown to predict outcome in patients with schizophrenia reliably. RESULTS: At 18-month follow-up, 37 participants had made the transition to psychosis. The SCPS total score was predictive of a first psychotic episode (P < 0.0001). SCPS items that remained as independent predictors in the Cox proportional hazard model were as follows: most usual quality of useful work in the past year (P = 0.006), quality of social relations (P = 0.006), presence of thought disorder, delusions or hallucinations in the past year (P = 0.001) and reported severity of subjective distress in past month (P = 0.003). CONCLUSION: The SCPS could make a valuable contribution to a more accurate prediction of psychosis in CHR subjects as a second-step tool. SCPS items assessing quality of useful work and social relations, positive symptoms and subjective distress have predictive value for transition. Further research should focus on investigating whether targeted early interventions directed at the predictive domains may improve outcomes. PMID- 22775301 TI - Dihydrophenanthrene-based metal-free dyes for highly efficient cosensitized solar cells. AB - Metal-free dyes (BP-1 to BP-3) containing a 9,10-dihydrophenanthrene unit in the spacer have been synthesized. The dye with the highest cell efficiency, BP-2, was used in combination with SQ2 for cosensitized DSSCs. The cosensitized DSSC in which the ratio of BP-2 and SQ2 is 8:2 (v/v) has a record high efficiency of 8.14% among cosensitized systems using all metal-free sensitizers. Dye distribution along the TiO2 film depth was analyzed by an Auger electron spectroscopy technique. PMID- 22775303 TI - Economic and environmental evaluation model for selecting the optimum design of green roof systems in elementary schools. AB - Green-roof systems offer various benefits to man and nature, such as establishing ecological environments, improving landscape and air quality, and offering pleasant living environments. This study aimed to develop an optimal-scenario selection model that considers both the economic and the environmental effect in applying GRSs to educational facilities. The following process was carried out: (i) 15 GRSs scenarios were established by combining three soil and five plant types and (ii) the results of the life cycle CO(2) analyses with the GRSs scenarios were converted to an economic value using certified emission reductions (CERs) carbon credits. Life cycle cost (LCC) analyses were performed based on these results. The results showed that when considering only the currently realized economic value, the conventional roof system is superior to the GRSs. However, the LCC analysis that included the environmental value, revealed that compared to the conventional roof system, the following six GRSs scenarios are superior (cost reduction; reduction ratio; in descending order): scenarios 13 ($195,229; 11.0%), 3 ($188,178; 10.6%), 8 ($181,558; 10.3%), 12 ($130,464; 7.4%), 2 ($124,566; 7.0%), and 7 ($113,931; 6.4%). Although the effect is relatively small in terms of cost reduction, environmental value attributes cannot be ignored in terms of the reduction ratio. PMID- 22775302 TI - Cortical silent period duration and its implications for surround inhibition of a hand muscle. AB - Surround inhibition is a neural mechanism that assists in the focusing of excitatory drive to muscles responsible for a given movement (agonist muscles) by suppressing unwanted activity in muscles not relevant to the movement (surround muscles). The purpose of the study was to determine the contribution of gamma aminobutyric acid(B) receptor-mediated intracortical inhibition, as assessed by the cortical silent period (CSP), to the generation of surround inhibition in the motor system. Eight healthy adults (five women and three men, 29.8 +/- 9 years) performed isometric contractions with the abductor digiti minimi (ADM) muscle in separate conditions with and without an index finger flexion movement. The ADM motor evoked potential amplitude and CSP duration elicited by transcranial magnetic stimulation were compared between a control condition in which the ADM was activated independently and during conditions involving three phases (pre motor, phasic, and tonic) of the index finger flexion movement. The motor evoked potential amplitude of the ADM was greater during the control condition compared with the phasic condition. Thus, the presence of surround inhibition was confirmed in the present study. Most critically, the CSP duration of the ADM decreased during the phasic stage of finger flexion compared with the control condition, which indicated a reduction of this type of intracortical inhibition during the phasic condition. These findings indicate that gamma-aminobutyric acid(B) receptor-mediated intracortical inhibition, as measured by the duration of the CSP, does not contribute to the generation of surround inhibition in hand muscles. PMID- 22775304 TI - How reliable are forensic evaluations of legal sanity? AB - When different clinicians evaluate the same criminal defendant's legal sanity, do they reach the same conclusion? Because Hawaii law requires multiple, independent evaluations when questions about legal sanity arise, Hawaii allows for the first contemporary study of the reliability of legal sanity opinions in routine practice in the United States. We examined 483 evaluation reports, addressing 165 criminal defendants, in which up to three forensic psychiatrists or psychologists offered independent opinions on a defendant's legal sanity. Evaluators reached unanimous agreement regarding legal sanity in only 55.1% of cases. Evaluators tended to disagree more often when a defendant was under the influence of drugs or alcohol at the time of the offense. But evaluators tended to agree more often when they agreed about diagnosing a psychotic disorder, or when the defendant had been psychiatrically hospitalized shortly before the offense. In court, judges followed the majority opinion among evaluators in 91% of cases. But when judges disagreed with the majority opinion, they usually did so to find defendants legally sane, rather than insane. Overall, this study indicates that reliability among practicing forensic evaluators addressing legal sanity may be poorer than the field has tended to assume. Although agreement appears more likely in some cases than others, the frequent disagreements suggest a need for improved training and practice. PMID- 22775305 TI - A trap for the unwary: jury decision making in cases involving the entrapment defense. AB - This article examines the opinions of jury-eligible participants regarding entrapment-related issues in online sex offender sting operations. Participants provided lower guilt ratings when the undercover officer initiated the online sexual solicitation than when the defendant initiated the online sexual solicitation. This effect was mediated by the causal attributions (situational vs. dispositional) made by mock jurors for the defendant's actions. The results also suggested that the entrapment defense was less successful for participants with a crime control orientation than for participants with a due process orientation. Based on the results, it is implied that law enforcement should exercise caution when performing these types of sting operations. Furthermore, defense and prosecuting attorneys should take into account the originators of the sexual solicitation when deciding whether to plea bargain or take a case to trial. PMID- 22775306 TI - The microRNA miR171h modulates arbuscular mycorrhizal colonization of Medicago truncatula by targeting NSP2. AB - Most land plants live symbiotically with arbuscular mycorrhizal fungi. Establishment of this symbiosis requires signals produced by both partners: strigolactones in root exudates stimulate pre-symbiotic growth of the fungus, which releases lipochito-oligosaccharides (Myc-LCOs) that prepare the plant for symbiosis. Here, we have investigated the events downstream of this early signaling in the roots. We report that expression of miR171h, a microRNA that targets NSP2, is up-regulated in the elongation zone of the root during colonization by Rhizophagus irregularis (formerly Glomus intraradices) and in response to Myc-LCOs. Fungal colonization was much reduced by over-expressing miR171h in roots, mimicking the phenotype of nsp2 mutants. Conversely, in plants expressing an NSP2 mRNA resistant to miR171h cleavage, fungal colonization was much increased and extended into the elongation zone of the roots. Finally, phylogenetic analyses revealed that miR171h regulation of NSP2 is probably conserved among mycotrophic plants. Our findings suggest a regulatory mechanism, triggered by Myc-LCOs, that prevents over-colonization of roots by arbuscular mycorrhizal fungi by a mechanism involving miRNA-mediated negative regulation of NSP2. PMID- 22775307 TI - Visceral and somatic disorders: tissue softening with frequency-specific microcurrent. AB - Frequency-specific microcurrent (FSM) is an emerging technique for treating many health conditions. Pairs of frequencies of microampere-level electrical stimulation are applied to particular places on the skin of a patient via combinations of conductive graphite gloves, moistened towels, or gel electrode patches. A consistent finding is a profound and palpable tissue softening and warming within seconds of applying frequencies appropriate for treating particular conditions. Similar phenomena are often observed with successful acupuncture, cranial-sacral, and other energy-based techniques. This article explores possible mechanisms involved in tissue softening. In the 1970s, neuroscientist and osteopathic researcher Irvin Korr developed a "gamma-loop hypothesis" to explain the persistence of increased systemic muscle tone associated with various somatic dysfunctions. This article summarizes how physiologists, neuroscientists, osteopaths, chiropractors, and fascial researchers have expanded on Korr's ideas by exploring various mechanisms by which injury or disease increase local muscle tension or systemic muscle tone. Following on Korr's hypothesis, it is suggested that most patients actually present with elevated muscle tone or tense areas due to prior traumas or other disorders, and that tissue softening indicates that FSM or other methods are affecting the cause of their pathophysiology. The authors believe this concept and the research it has led to will be of interest to a wide range of energetic, bodywork, and movement therapists. PMID- 22775308 TI - Dynamic changes in MELD score not only predict survival on the waiting list but also overall survival after liver transplantation. AB - The predictive value of MELD score for post-transplant survival has been under constant debate since its implementation in 2001. Aim of this study was to assess the impact of alterations in MELD score throughout waiting time (WT) on post transplant survival. A single-centre retrospective analysis of 1125 consecutive patients listed for liver transplantation between 1997 and 2009 was performed. The impact of MELD score and dynamic changes in MELD score (DeltaMELD), as well as age, sex, year of listing and WT were evaluated on waiting list mortality and post-transplant survival. In this cohort, 539 (60%) patients were transplanted, 223 (25%) died on list and 142 (15%) were removed from the waiting list during WT. One-, three- and five-year survival after liver transplantation were 83%, 78% and 76% respectively. DeltaMELD as a continuous variable proved to be the only significant risk factor for overall survival after liver transplantation (hazard ratio (HR): 1.06, 95% confidence interval (CI) 1.02-1.1, P = 0.013). The highest risk of post-transplant death could be defined for patients with a DeltaMELD > 10 (HR: 4.87, 95% CI 2.09-11.35, P < 0.0001). In addition, DeltaMELD as well as MELD at listing showed a significant impact on waiting list mortality. DeltaMELD may provide an easy evaluation tool to identify patients on the liver transplant waiting list with a high mortality risk after transplantation in the current setting. Temporarily withholding and re-evaluating these patients might improve overall outcome after liver transplantation. PMID- 22775309 TI - Effects of a multi-component responsible beverage service programme on violent assaults in Sweden. AB - AIM: A multi-component Responsible Beverage Service (RBS) programme has been disseminated in Swedish municipalities. The aim of the programme is to reduce violence associated with consumption of alcohol at on-licensed premises. This study aimed to analyse the effect of the programme on police-recorded assaults after the dissemination of the programme in Swedish municipalities, 1996-2009. DESIGN: This study is a natural experiment that uses variation in the level of implementation of the RBS programme to predict change in the rate of police recorded assaults. SETTING: Swedish municipalities. PARTICIPANTS: The municipalities included in the study initiated the RBS programme no later than 2008. On-licensed premises open during the evenings must exist. Of 290 municipalities, 237 fulfilled these requirements. MEASUREMENT: Programme fidelity was studied by means of several surveys. Yearly data on police-recorded assaults, per 100,000 inhabitants aged 15 and above, committed on weekend nights, were used as dependent variable. A fixed-effects panel data regression model was used to examine the effect of the programme. FINDINGS: Each extension of the programme, by one component, was associated with a significant 3.1% reduction in assaults. However, this effect was seen mainly in smaller municipalities. Of the different components of the programme, the presence of a community coalition steering group had a significant effect on assaults. No significant effect was found regarding RBS training or supervision of on-licensed premises. CONCLUSION: Multi-component Responsible Beverage Service programmes can have a significant effect on police recorded assaults even when implemented on a large scale in many communities. PMID- 22775310 TI - Compartmentalization and spatiotemporal organization of macromolecules in bacteria. AB - For many years, the bacterial cells were regarded as tiny vessels lacking internal organization. This view, which stemmed from the scarcity of membrane bounded organelles, has changed considerably in recent years, mainly due to advancements in imaging capabilities. Consequently, despite the rareness of conventional organelles, bacteria are now known to have an intricate internal organization, which is vital for many cellular processes. The list of bacterial macromolecules reported to have distinct localization patterns is rapidly growing. Moreover, time-lapse imaging revealed the spatiotemporal dynamics of various bacterial macromolecules. Although the regulatory mechanisms that underlie macromolecules localization in bacterial cells are largely unknown, certain strategies elucidated thus far include the establishment of cell polarity, the employment of cytoskeletal proteins, and the use of the membrane properties, that is, curvature, electric potential, and composition, as localization signals. The most surprising mechanism discovered thus far is targeting of certain mRNAs to the subcellular domains where their protein products are required. This mechanism relies on localization features in the mRNA itself and does not depend on translation. Localization of other mRNAs near their genetic loci suggests that the bacterial chromosome is involved in organizing gene expression. Taken together, the deep-rooted separation between cells with nucleus and without is currently changing, highlighting bacteria as suitable models for studying universal mechanisms underlying cell architecture. PMID- 22775311 TI - Associations between complications and health-related quality of life in individuals with diabetes. AB - OBJECTIVE: Type 2 diabetes and associated complications adversely affect health related quality of life (HRQoL). However, it is unclear whether different complications have the same or different associations with HRQoL. We examined associations between retinopathy, nephropathy, peripheral neuropathy (microvascular), coronary heart disease, stroke and peripheral arterial disease (macrovascular) in diabetes and HRQoL. DESIGN: This study was a follow-up examination between 2004 and 2007 of participants from four previous cross sectional population-based studies in Singapore. METHODS: Health-related quality of life was assessed through self-administered SF-36 health survey version 2. Diabetes and complications status were assessed through self-report, clinical and laboratory examinations. About 2601 individuals, 2205 healthy and 396 with diabetes, were studied. RESULTS: Lower physical component scores (PCS) were associated with microvascular (2.96 points, P < 0.001) and both macro- and microvascular complications (4.67 points, P < 0.001), but not diabetes alone. Coronary heart disease (3.86 points, P = 0.007), peripheral neuropathy (11.46 points, P < 0.001) and severe retinopathy (4.46 points, P < 0.001) were associated with lower PCS. The greatest reduction in scores was seen in peripheral neuropathy. CONCLUSIONS: Quality of life in patients with diabetes is affected mainly by presence of complications, and not diabetes per se. Peripheral neuropathy was associated with the greatest reduction in quality of life. Improved management to prevent or delay onset of complications may reduce the effect on quality of life in patients with diabetes. PMID- 22775312 TI - Porous Pr(OH)3 nanostructures as high-efficiency adsorbents for dye removal. AB - Herein we report the electrochemical synthesis of porous Pr(OH)(3) nanobelt arrays (NBAs), nanowire arrays (NWAs), nanowire bundles (NWBs), and nanowires (NWs) and their applications as dye absorbents in water treatment. These Pr(OH)(3) nanostructures exhibit high efficient and selective adsorption of the dyes with amine (-NH(2)) functional groups such as Congo red, reactive yellow, and reactive blue. The high efficiency and selectivity is attributed to the large effective surface area of the porous structure, plentiful hydroxyl groups, and basic sites on the Pr(OH)(3) surface. Furthermore, the toxicity studies of these porous Pr(OH)(3) nanostructure show a negligible effect on seed germination, indicating that they hold great potential as environmentally friendly absorbents in water treatment. PMID- 22775313 TI - Refining the prognostic importance of the diversity of FLT3 internal tandem duplications. PMID- 22775314 TI - Pilot study of dacetuzumab in combination with rituximab and gemcitabine for relapsed or refractory diffuse large B-cell lymphoma. AB - Dacetuzumab, a CD40-targeted, humanized antibody, mediates antitumor activity through effector cell functions and direct apoptotic signal transduction. Preclinical studies demonstrated synergistic activity between dacetuzumab, gemcitabine and rituximab against non-Hodgkin lymphoma in vivo. A phase 1b safety/efficacy study of dacetuzumab in combination with rituximab and gemcitabine was conducted in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received dacetuzumab at doses of 8 or 12 mg/kg IV weekly with rituximab (375 mg/m(2) IV weekly in cycle 1, then every 28 days) and gemcitabine (1000 mg/m(2) IV, days 1, 8 and 15, or days 1 and 15). Thirty-three patients with a median age of 67 years were enrolled. Common adverse events (>= 15%) were grade 1/2 cytokine release syndrome, nausea, fatigue, thrombocytopenia, headache, decreased appetite, dyspnea, neutropenia, pyrexia, anemia, diarrhea, edema, constipation and cough. Dacetuzumab-related grade 3/4 adverse events occurred infrequently. Six of 30 evaluable patients achieved a complete response (CR) and eight a partial response (PR) per investigator assessment for an overall response rate (ORR) of 47%. PMID- 22775316 TI - Media portrayals of the female condom. AB - This study examines newspaper and broadcast news depictions of the female condom from 1993 to 2009 in the three major television networks (ABC, CBS, and NBC), and in 8 of 10 top daily newspapers and 3 of 4 national newspapers published in the United States, according to circulation figures as of September 30, 2008. Given the high rates of sexually transmitted infections in the United States and their effect on women, particularly those between 15 and 24 years of age, it is important to examine media sources and the health information that the public is or is not receiving through these sources. This study (a) examines whether the female condom was depicted positively or negatively in broadcast and newspaper coverage, (b) determines the ways in which the female condom was compared with the male condom and with other contraceptives, and (c) identifies the sources used by journalists in female condom portrayals. The authors discuss the implications of the coverage of the female condom by broadcast and print news. PMID- 22775318 TI - Double-headed sulfur-linked amino acids as first inhibitors for betaine homocysteine S-methyltransferase 2. AB - Betaine-homocysteine S-methyltransferase 2 (BHMT-2) catalyzes the transfer of a methyl group from S-methylmethionine to l-homocysteine, yielding two molecules of l-methionine. It is one of three homocysteine methyltransferases in mammals, but its overall contribution to homocysteine remethylation and sulfur amino acid homeostasis is not known. Moreover, recombinant BHMT-2 is highly unstable, which has slowed research on its structural and catalytic properties. In this study, we have prepared the first series of BHMT-2 inhibitors to be described, and we have tested them with human recombinant BHMT-2 that has been stabilized by copurification with human recombinant BHMT. Among the compounds synthesized, (2S,8RS,11RS)-5-thia-2,11-diamino-8-methyldodecanedioic acid (11) was the most potent (K(i)(app) ~77 nM) and selective inhibitor of BHMT-2. Compound 11 only weakly inhibited human BHMT (IC(50) about 77 MUM). This compound (11) may be useful in future in vivo studies to probe the physiological significance of BHMT 2 in sulfur amino acid metabolism. PMID- 22775317 TI - Add-on therapies to metformin in type 2 diabetes: what modulates the respective decrements in postprandial and basal glucose? AB - BACKGROUND: Oral hypoglycemic agents (OHAs) are usually divided into postprandial and basal drugs. As their actions are probably more complex, it is important to ascertain which factors can modulate their effects. SUBJECTS AND METHODS: Thirty one type 2 diabetes patients treated with metformin (glycosylated hemoglobin [HbA1c] 6.5-9%; median, 7.3%) and enrolled in two randomized controlled studies were allocated to either rosiglitazone (Group 1, n = 8) or glimepiride (Group 2, n = 7) and to either vildagliptin or sitagliptin (Group 3 considered as a whole, n = 16). All patients were investigated using continuous glucose monitoring at baseline and after 8-12 weeks of add-on therapy. Areas under the 24-h glycemic profile curves (AUCs) were determined for assessing postprandial (AUCpp), basal (AUCb), and total (AUCtotal) hyperglycemia. After calculation of decrements in AUCs (?AUCs) from baseline to end of treatment periods, the following contribution ratios of postprandial and basal decrements to the overall glucose decrement were determined: ?AUCpp/?AUCtotal and ?AUCb/?AUCtotal (%). RESULTS: ?AUCpp/?AUCtotal and ?AUCb/?AUCtotal were negatively and positively, respectively, associated (R(2) = 0.195, P = 0.013) with baseline HbA1c. ?AUCpp/?AUCtotal was significantly higher (50.8 +/- 4.8%) in patients with HbA1c <7.3% than in those with HbA1c >= 7.3% (27.0 +/- 4.4%) (P = 0.001). After adjustment on baseline HbA1c, ?AUCpp/?AUCtotal was greater in Group 3 (44.0 +/- 1.6%) than in Group 1 (32.1 +/- 4%) and 2 (37.0 +/- 3.1%) (P = 0.007). CONCLUSIONS: Gliptins, glitazones and sulfonylureas concomitantly act on basal and postprandial glucose even though gliptins are more efficient on postprandial glucose. HbA1c appears as a reliable factor for predicting the respective decrements of these two parameters and thus for guiding the choice between the aforementioned drugs. PMID- 22775320 TI - A case of Pyrola plantlets with picky palates leads to new insights on mycoheterotrophic seedlings and the fungi that feed them. PMID- 22775321 TI - Like a jungle sometimes: how leaves survive in the rainforest understory. PMID- 22775322 TI - What you smell is more important than what you see? Natural selection on floral scent. PMID- 22775323 TI - Integrating empirical-modeling approaches to improve understanding of terrestrial ecology processes. PMID- 22775324 TI - Residues required for activity in Escherichia coli o-succinylbenzoate synthase (OSBS) are not conserved in all OSBS enzymes. AB - Understanding how enzyme specificity evolves will provide guiding principles for protein engineering and function prediction. The o-succinylbenzoate synthase (OSBS) family is an excellent model system for elucidating these principles because it has many highly divergent amino acid sequences that are <20% identical, and some members have evolved a second function. The OSBS family belongs to the enolase superfamily, members of which use a set of conserved residues to catalyze a wide variety of reactions. These residues are the only conserved residues in the OSBS family, so they are not sufficient to determine reaction specificity. Some enzymes in the OSBS family catalyze another reaction, N-succinylamino acid racemization (NSAR). NSARs cannot be segregated into a separate family because their sequences are highly similar to those of known OSBSs, and many of them have both OSBS and NSAR activities. To determine how such divergent enzymes can catalyze the same reaction and how NSAR activity evolved, we divided the OSBS family into subfamilies and compared the divergence of their active site residues. Correlating sequence conservation with the effects of mutations in Escherichia coli OSBS identified two nonconserved residues (R159 and G288) at which mutations decrease efficiency >=200-fold. These residues are not conserved in the subfamily that includes NSAR enzymes. The OSBS/NSAR subfamily binds the substrate in a different orientation, eliminating selective pressure to retain arginine and glycine at these positions. This supports the hypothesis that specificity-determining residues have diverged in the OSBS family and provides insight into the sequence changes required for the evolution of NSAR activity. PMID- 22775325 TI - From mouse to humans: discovery of the CACNG2 pain susceptibility gene. AB - Chronic pain is a major healthcare problem affecting the daily lives of millions with enormous financial costs. The notorious variability and lack of efficient pain relief pharmaceuticals provide both genetic and therapeutic challenge. There are several genetic approaches that aim to uncover the molecular nature of pain phenotypes into their genetic components. Gene mapping using model organisms for various pain phenotypes has led to the identification of novel genes affecting susceptibility and response to pain stimuli. Translational studies have succeeded to tie those genes to human pain syndromes, thus suggesting new targets for drug discovery. In this short review, a perspective on pain genetics and the trajectory from pain phenotype to pain gene involving fine-mapping strategies, bioinformatic analysis and microarray profiling alongside human association analysis will be introduced. This integrated approach has led to identification of CACNG2 as a novel neuropathic pain gene affecting pain susceptibility both in mice and humans. It also serves as a prototype for efficient and economic discovery of pain genes. Comparisons to other methods as well as future directions of pain genetics will be discussed as well. PMID- 22775326 TI - Octopaminergic modulation of contrast gain adaptation in fly visual motion sensitive neurons. AB - Locomotor activity like walking or flying has recently been shown to alter visual processing in several species. In insects, the neuromodulator octopamine is thought to play an important role in mediating state changes during locomotion of the animal [K.D. Longden & H.G. Krapp (2009) J. Neurophysiol., 102, 3606-3618; (2010) Front. Syst. Neurosci., 4, 153; S.N. Jung et al. (2011)J. Neurosci., 31, 9231-9237]. Here, we used the octopamine agonist chlordimeform (CDM) to mimic effects of behavioural state changes on visual motion processing. We recorded from identified motion-sensitive visual interneurons in the lobula plate of the blowfly Calliphora vicina. In these neurons, which are thought to be involved in visual guidance of locomotion, motion adaptation leads to a prominent attenuation of contrast sensitivity. Following CDM application, the neurons maintained high contrast sensitivity in the adapted state. This modulation of contrast gain adaptation was independent of the activity of the recorded neurons, because it was also present after stimulation with visual motion that did not result in deviations from the neurons' resting activity. We conclude that CDM affects presynaptic inputs of the recorded neurons. Accordingly, the effect of CDM was weak when adapting and test stimuli were presented in different parts of the receptive field, stimulating separate populations of local presynaptic neurons. In the peripheral visual system adaptation depends on the temporal frequency of the stimulus pattern and is therefore related to pattern velocity. Contrast gain adaptation could therefore be the basis for a shift in the velocity tuning that was previously suggested to contribute to state-dependent processing of visual motion information in the lobula plate interneurons. PMID- 22775327 TI - Cradle-to-gate life cycle assessment for a cradle-to-cradle cycle: biogas-to bioplastic (and back). AB - At present, most synthetic organic materials are produced from fossil carbon feedstock that is regenerated over time scales of millions of years. Biobased alternatives can be rapidly renewed in cradle-to-cradle cycles (1-10 years). Such materials extend landfill life and decrease undesirable impacts due to material persistence. This work develops a LCA for synthesis of polyhydroxybutyrate (PHB) from methane with subsequent biodegradation of PHB back to biogas (40-70% methane, 30-60% carbon dioxide). The parameters for this cradle-to-cradle cycle for PHB production are developed and used as the basis for a cradle-to-gate LCA. PHB production from biogas methane is shown to be preferable to its production from cultivated feedstock due to the energy and land required for the feedstock cultivation and fermentation. For the PHB-methane cycle, the major challenges are PHB recovery and demands for energy. Some or all of the energy requirements can be satisfied using renewable energy, such as a portion of the collected biogas methane. Oxidation of 18-26% of the methane in a biogas stream can meet the energy demands for aeration and agitation, and recovery of PHB synthesized from the remaining 74-82%. Effective coupling of waste-to-energy technologies could thus conceivably enable PHB production without imported carbon and energy. PMID- 22775328 TI - Quantum dot cytotoxicity and ways to reduce it. AB - The dramatic increase in the use of nanoparticles (NP) in industry and research has raised questions about the potential toxicity of such materials. Unfortunately, not enough is known about how the novel, technologically attractive properties of NPs correlate with the interactions that may take place at the nano/bio interface. The academic, industrial, and regulatory communities are actively seeking answers to the growing concerns on the impact of nanotechnology on humans. In this Account we adopt quantum dots (QDs) as an illustrative example of the difficulties associated with the development of a rational science-based approach to nanotoxicology. The optical properties of QDs are far superior to those of organic dyes in terms of emission and absorption bandwidths, quantum yield, and resistance to photobleaching. Moreover, QDs may be decorated with targeting moieties or drugs and, therefore, are candidates for site-specific medical imaging and for drug delivery, for example in cancer treatment. Earlier this year researchers demonstrated that QD-based imaging using monkeys caused no adverse effects although QDs accumulated in lymph nodes, bone marrow, liver, and spleen for up to 3 months after injection. Such persistence of QDs in live animals does, however, raise concerns about the safety of using QDs both in the laboratory and in the clinic. Researchers anticipate that QDs will be increasingly used not only in clinical applications but also in various manufactured products. For example, QD-solar cells have emerged as viable contenders to complement or replace dye-sensitized solar cells; CdTe/CdS thin film cells have already captured approximately 10 percent of the global market, and in addition, QDs can serve as components of sensors and as emitting materials in LEDs. Given the clear indications that QDs will inevitably become components of a wide range of manufactured and consumer products, researchers and policy makers need to understand the possible health risks associated with exposure to QDs. In this Account, we initially review the known mechanisms by which QDs can damage cells, including oxidative stress elicited by reactive oxygen species (ROS). We discuss lesser-known impairments induced in cells by nanomolar to picomolar concentrations of QDs, which imply that cadmium-containing QDs can exert genotoxic, epigenetic, and metalloestrogenic effects. These observations strongly suggest that minute concentrations of QDs could be sufficient to cause long lasting, even transgenerational, effects. We also consider various modes by which humans could be exposed to QDs in their work or through the environment. Although considerable advances have been made in enhancing the stability and overall quality of QDs, over time they can partially degrade in the environment or in biological systems, and eventually cause small, but cumulative undesirable effects. A combination of toxicological, genetic, epigenetic and imaging approaches is required to create comprehensive guidelines for evaluating the nanotoxicity of nanomaterials, including QDs. Prior to biological investigations with these materials, an indispensible step must be the full characterization of NPs by complementary techniques. Specifically, the concentration, size, charge, and ligand stability of NPs in biological media must be known if we are to understand fully how the properties of nanoparticles and of their biological environment contribute to cytotoxicity. PMID- 22775329 TI - An adjunct intervention for management of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). AB - OBJECTIVES: Application of transcutaneous electrical nerve stimulation over acupuncture points (Acu-TENS) is a noninvasive intervention that has recently been shown to alleviate dyspnea in patients with stable chronic obstructive pulmonary disease (COPD). This case report aims to explore the role of Acu-TENS in patients diagnosed with COPD during the acute exacerbation. STUDY DESIGN: The study design was a case report. SETTING: The study was conducted in an inpatient setting. SUBJECT: The subject was a 74-year-old man admitted to the hospital due to acute exacerbation of COPD (AECOPD). INTERVENTION: Treatment consisted of application of TENS on EX-B1 (Dingchuan) for 45 minutes. OUTCOME MEASURES: Oxygen saturation, heart rate, and dyspnea score were measured before, immediately after, and 45 minutes after Acu-TENS intervention. Other than the physiologic measures, 10 mL of venous blood was taken from the cubital vein for assessment of beta-endorphin level, white blood cell count, tumor necrosis factor-alpha (TNF alpha), and C-reactive protein (CRP) level before and immediately postintervention. RESULTS: Postintervention, improved oxygen saturation, and reduction in heart rate and dyspneic sensation were observed accompanied by a raised blood beta-endorphin level but the level of white blood cell count, TNF alpha, and CRP remain unchanged. CONCLUSIONS: Application of 45 minutes Acu-TENS appeared to alleviate symptoms in a patient with AECOPD. The role of adjunctive Acu-TENS therapy during acute exacerbation warrants further investigation. PMID- 22775330 TI - Kinetic analysis of porcine fibroblast reprogramming toward pluripotency by defined factors. AB - Induced pluripotent stem cells (iPSCs) are generated from somatic cells through ectopic expression of defined transcription factors. So far, many iPSC lines have been established in various species, including porcine. However, the molecular events during somatic cell reprogramming in pig are largely unknown. The aim of this study was to carry out porcine embryonic fibroblast (PEF) reprogramming by using mouse transcription factors and to monitor morphological and biological progress systematically at an early stage of cell reprogramming. The retrovirus infected PEF cells retained the four transgenes used and showed morphological changes and alkaline phosphatase staining at day 5 after infection. The endogenous OCT4, NANOG, and TERT genes were activated, and their expression levels were increased significantly. BAX gene expression, a proapoptotic member of the BCL-2 family, was also increased at day 5, suggesting that c-Myc might trigger cell apoptosis. Omission of c-Myc from the cocktail of factors then greatly influenced the reprogramming efficiency and lowered the formation of iPSC colonies. The expression of paternally imprinted DLK1 and DIO3 was slightly downregulated after infection, but then recovered within 2 weeks. However, the expression of maternally imprinted GTL2 was silenced aberrantly at a very early stage of infection and did not recover. Together, these observations illustrated that upregulation of pluripotent-related gene expression, stabilizing the imprinted Dlk1-Dio3 domain, and inhibition of apoptotic events might be conductive to the promotion of the reprogramming process to produce complete porcine iPSCs. PMID- 22775331 TI - The Arabidopsis B-type response regulator 18 homomerizes and positively regulates cytokinin responses. AB - In higher plants, the two-component system (TCS) is a signaling mechanism based on a His-to-Asp phosphorelay. The Arabidopsis TCS involves three different types of proteins, namely the histidine kinases (AHKs), the histidine phosphotransfer proteins (AHPs) and the response regulators (ARRs). The ARRs comprise three different families, namely A, B and C types, according to their protein structure. While some members of the B-type family of ARRs have been studied extensively and reported to act as DNA-binding transcriptional regulators, very limited information is available for other B-type ARRs such as ARR18. In this study, we characterize in detail the molecular and functional properties of ARR18. ARR18 acts as a transcriptional regulator in plant cells and forms homodimers in planta as shown by FRET-FLIM studies. As demonstrated by mutational analysis, the aspartate at position 70 (D70) in the receiver domain of ARR18 acts as crucial phosphorylation site. The modification of D70 affects the response regulator's ability to homodimerize and to activate its target genes. Furthermore, physiological investigations of Arabidopsis lines ectopically expressing ARR18 introduce ARR18 as a new member within the cytokinin-regulated response pathway regulating root elongation. PMID- 22775332 TI - Development of dependence following treatment with opioid analgesics for pain relief: a systematic review. AB - AIMS: To assess the incidence or prevalence of opioid dependence syndrome in adults (with and without previous history of substance abuse) following treatment with opioid analgesics for pain relief. METHODS: Medline, Embase, CINHAL and the Cochrane Library were searched up to January 2011. Systematic reviews and primary studies were included if they reported data about incidence or prevalence of opioid dependence syndrome (as defined by DSM-IV or ICD-10) in patients receiving strong opioids (or opioid-type analgesics) for treatment of acute or chronic pain due to any physical condition. The data were abstracted, and the methodological quality was assessed using validated checklists. RESULTS: Data were extracted from 17 studies involving a total of 88 235 participants. The studies included three systematic reviews, one randomized controlled trial, eight cross-sectional studies and four uncontrolled case series. Most studies included adult patients with chronic non-malignant pain; two also included patients with cancer pain; only one included patients with a previous history of dependence. Incidence ranged from 0 to 24% (median 0.5%); prevalence ranged from 0 to 31% (median 4.5%). CONCLUSIONS: The available evidence suggests that opioid analgesics for chronic pain conditions are not associated with a major risk for developing dependence. PMID- 22775333 TI - Improved GFR and renal plasma perfusion following remote ischaemic conditioning in a porcine kidney transplantation model. AB - Delayed graft function (DGF) complicates approximately 25% of kidney allografts donated after brain death (DBD). Remote ischaemic conditioning (rIC) involves brief, repetitive, ischaemia in a distant tissue in connection with ischaemia/reperfusion in the target organ. rIC has been shown to induce systemic protection against ischaemic injuries. Using a porcine kidney transplantation model with donor (63 kg) recipient (15 kg) size mismatch, we investigated the effects of recipient rIC on early renal plasma perfusion and GFR. Brain death was induced in donor pigs (n = 8) and kidneys were removed and kept in cold storage until transplantation. Nephrectomized recipient pigs were randomized to rIC (n = 8) or non-rIC (n = 8) with one kidney from the same donor in each group. rIC consisted of 4 * 5 min clamping of the abdominal aorta. GFR was significantly higher in the rIC group compared with non-rIC (7.2 ml/min vs. 3.4 ml/min; DeltaGFR = 3.7 ml/min, 95%-CI: 0.3-7.2 ml/min, P = 0.038). Renal plasma perfusion in both cortex and medulla measured by dynamic contrast-enhanced magnetic resonance imaging (MRI) was significantly higher over time in the rIC group compared with non-rIC. This experimental study demonstrated a positive effect of rIC on early graft perfusion and function in a large animal transplantation model. PMID- 22775334 TI - Spectroscopic and calorimetric evaluation of chemically induced protein denaturation in HuH-7 liver cancer cells and impact on cell survival. AB - Solid tumors such as hepatocellular carcinoma are very often not amenable to chemotherapy and radiotherapy. Local ablation methods, including chemical ablation with absolute ethanol, are therefore an option for treatment but lack of information about the mechanism of devitalization leading to cell death is a hindrance to further adoption. Systemic toxicity also has limited the amount of ethanol that can be used in a single treatment session. Therefore we evaluated the mechanism of urea, a denaturant with little or no systemic toxicity, for potential use in chemical ablation. In this study we report on the use of three methods to analyze the effects in cell culture with a view towards eventual clinical application. Human hepatoma HuH-7 cells were analyzed at several time points after treatment using FTIR, DSC, and Raman microspectroscopy based on MTT and PI-exclusion viability assays. Time course fractional denaturation data plotted against viability show that a 50% viability drop occurs after only a 10 20% drop in overall protein denaturation. Other methods of cell death such as apoptosis may also be operative, but this result implies that protein denaturation is one of the major mechanisms of cell death. This is in line with what has been previously suggested for purely thermal methods, and opens the way to mechanism-based improvements in chemical ablation of solid tumors. PMID- 22775335 TI - Ovarian tumor characterization using 3D ultrasound. AB - Among gynecological malignancies, ovarian cancer is the most frequent cause of death. Preoperative determination of whether a tumor is benign or malignant has often been found to be difficult. Because of such inconclusive findings from ultrasound images and other tests, many patients with benign conditions have been offered unnecessary surgeries thereby increasing patient anxiety and healthcare cost. The key objective of our work is to develop an adjunct Computer Aided Diagnostic (CAD) technique that uses ultrasound images of the ovary and image mining algorithms to accurately classify benign and malignant ovarian tumor images. In this algorithm, we extract texture features based on Local Binary Patterns (LBP) and Laws Texture Energy (LTE) and use them to build and train a Support Vector Machine (SVM) classifier. Our technique was validated using 1000 benign and 1000 malignant images, and we obtained a high accuracy of 99.9% using a SVM classifier with a Radial Basis Function (RBF) kernel. The high accuracy can be attributed to the determination of the novel combination of the 16 texture based features that quantify the subtle changes in the images belonging to both classes. The proposed algorithm has the following characteristics: cost effectiveness, complete automation, easy deployment, and good end-user comprehensibility. We have also developed a novel integrated index, Ovarian Cancer Index (OCI), which is a combination of the texture features, to present the physicians with a more transparent adjunct technique for ovarian tumor classification. PMID- 22775336 TI - A bio-mathematical model for parallel organs and its use in ranking radiation treatment plans. AB - To develop a new bio-mathematical model, named LQ-based parallel-organ model, that can overcome the limitation of interpreting the simple dose-volume information so as to rank the radio- toxicity of parallel organs in the same patient. A parallel organ consists of Function Subunits (FSUs), with each FSU being equal and representative in functional status. Based on the Linear Quadratic model (LQ model), we had derived a bio-mathematical model to calculate the survival cell number for radiation dose response. We then compared the cell survival number for the ranking of treatment plans for the same patient. Ninety 3D plans from forty-five randomly selected lung cancer patients were generated using the ELEKTA precise 2.12 treatment planning system. The LQ-based parallel organ model was tested against the widely used Lyman-Kutcher-Burman model (LKB model). There was no distinct statistical difference in plan ranking between using the LQ-based parallel-organ model and the LKB model (P = 0.475). Ranking plans by the V(x), Mean Lung Dose (MLD) and the LQ-based parallel-organ model shows that there was no distinct statistical difference between V(5), V(10), V(20), MLD and the LQ-based parallel-organ model, respectively (all Ps > 0.05). The proposed LQ-based parallel-organ model was found to be efficient and reliable for ranking treatment plans for the same patient. PMID- 22775337 TI - Radiobiological evaluation of breast cancer radiotherapy accounting for the effects of patient positioning and breathing in dose delivery. A meta analysis. AB - In breast cancer radiotherapy, significant discrepancies in dose delivery can contribute to underdosage of the tumor or overdosage of normal tissue, which is potentially related to a reduction of local tumor control and an increase of side effects. To study the impact of these factors in breast cancer radiotherapy, a meta analysis of the clinical data reported by Mavroidis et al. (2002) in Acta Oncol (41:471-85), showing the patient setup and breathing uncertainties characterizing three different irradiation techniques, were employed. The uncertainties in dose delivery are simulated based on fifteen breast cancer patients (5 mastectomized, 5 resected with negative node involvement (R-) and 5 resected with positive node involvement (R1)), who were treated by three different irradiation techniques, respectively. The positioning and breathing effects were taken into consideration in the determination of the real dose distributions delivered to the CTV and lung in each patient. The combined frequency distributions of the positioning and breathing distributions were obtained by convolution. For each patient the effectiveness of the dose distribution applied is calculated by the Poisson and relative seriality models and a set of parameters that describe the dose-response relations of the target and lung. The three representative radiation techniques are compared based on radiobiological measures by using the complication-free tumor control probability, P(+) and the biologically effective uniform dose, (BEUD)concepts. For the Mastectomy case, the average P(+) values of the planned and delivered dose distributions are 93.8% for a (BEUD)(CTV) of 51.8 Gy and 85.0% for a (BEUD)(CTV) of 50.3 Gy, respectively. The respective total control probabilities, P(B) values are 94.8% and 92.5%, whereas the corresponding total complication probabilities, P(1) values are 0.9% and 7.4%. For the R- case, the average P(+) values are 89.4% for a (BEUD)(CTV) of 48.9 Gy and 88.6% for a (BEUD)(CTV) of 49.2 Gy and 85.5% for a (BEUD)(CTV) of 49.1 Gy, respectively. The respective PB values are 90.2% and 90.1%, whereas the corresponding P(+) values are 4.1% and 4.6%. The combined effects of positioning uncertainties and breathing can introduce a significant deviation between the planned and delivered dose distributions in lung in breast cancer radiotherapy. The positioning and breathing uncertainties do not affect much the dose distribution to the CTV. The simulated delivered dose distributions show larger lung complication probabilities than the treatment plans. This means that in clinical practice the true expected complications are underestimated. Radiation pneumonitis of Grade 1-2 is more frequent and any radiotherapy optimization should use this as a more clinically relevant endpoint. PMID- 22775338 TI - Dielectrophoretic separation of prostate cancer cells. AB - Separation of cancer cells from other biological materials is significant for circulating tumor cell detection in cancer diagnosis and treatment. However, separation of one type of cancer cell from other types of cancer cells can be difficult, since they share similar morphology and biomarkers. In the present work, we have successfully manipulated and isolated LNCaP prostate cancer cells from HCT116 colorectal cancer cells, by dielectrophoresis (DEP) in a microfluidic platform in a continuous operation. In this cell sorter, the prostate cancer cells were treated as target cells and were deflected to a side channel from a main channel as they experienced a negative DEP force, when an AC electric field at the cross-over frequency of the HCT116 cells was supplied. This motion consequently led to the separation of the prostate cancer cells from the colorectal cancer cells. In this manuscript, we report the flow conditions, DEP spectra of the cancer cells and the isolation of LNCaP cells from HCT116 cells. The separation and enrichment factor have been investigated as well. PMID- 22775339 TI - A comparison of critical structure dose and toxicity risks in patients with low grade gliomas treated with IMRT versus proton radiation therapy. AB - Proton therapy offers dosimetric advantage of decreased dose to non-target tissues. This study explored the potential benefits of proton radiation therapy versus photon based intensity modulated radiation therapy (IMRT) for patients with low grade gliomas (LGG) through dosimetric comparison and biological modeling of potential radiation-induced toxicities. Eleven patients were treated with fractionated proton radiation therapy on a prospective protocol assessing for feasibility and treatment toxicity of proton radiation therapy in patients with LGG. IMRT treatment plans were created for each patient using the same CT planning data set and defined structures. The prescription dose to clinical target volume (CTV) was 54 Gy(RBE). The toxicity risk of IMRT and protons was estimated based upon equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) modeling. The risk of secondary tumors for each modality was estimated. Proton EUD for most immediate normal tissue structures was between 10 20 Gy lower than the EUD delivered by IMRT. However, the difference in NTCP was negligible for both modalities. The mean excess risk of proton radiation-induced second tumor in the brain per 10,000 cases per year is 47 (range 11-83), while the mean risk for IMRT is 106 (range 70-134). The mean ratio of excess risk IMRT/protons is 2.2 (range 1.6-6.5), demonstrating that the risk of secondary tumors is consistently higher for IMRT. Proton therapy effectively reduces the dose to surrounding normal tissues in LGG patients. IMRT has a twofold higher risk of secondary intracranial tumors as compared to proton therapy. In most cases, NTCP is negligible for both modalities. The benefit of proton therapy over IMRT may be more substantial in patients with tumors in proximity to critical structures. PMID- 22775340 TI - Glioma stem-like cells are less susceptible than glioma cells to sonodynamic therapy with photofrin. AB - Despite remarkable progress in diagnosis and treatment, malignant glioma, a highly lethal cancer of the central nervous system, remains incurable. Although glioma stem-like cells (GSCs) represent a relatively small fraction of the cells in malignant glioma, they can proliferate and self renew extensively, being crucial for tumor recurrence. Cancer treatment by sonodynamic therapy (SDT) chiefly depends on antitumor effects of reactive oxygen species (ROS) generated from a sonosensitizer activated by ultrasound. Although SDT effectively kills glioma cells, its efficiency against GSCs is not established. We attempted to compare the susceptibility of GSCs to SDT, using Photofrin, a porphyrin derivative photosensitizer, with that of glioma cells. Cell viability and apoptosis assays showed that SDT damaged both GSCs and U251 glioma cells, but GSCs were significantly less susceptible to SDT (p < 0.01). To elucidate the mechanism of the antitumor effects of SDT, we evaluated intracellular ROS production and Photofrin uptake: ROS production and Photofrin content were significantly lower (p < 0.01) in GSCs than in U251 glioma cells. Thus, cellular differences in sonosensitizer uptake and ROS production influence the antitumor effects of SDT. Furthermore, the resistance of GSCs may be caused by decreased sonosensitizer uptake due to ABCG2 overexpression. PMID- 22775341 TI - Common mental disorders and long-term sickness absence in a general working population. The Hordaland Health Study. AB - OBJECTIVE: To examine and compare the prospective effect of the common mental disorders (CMD) anxiety and depression on duration and recurrence of sickness absence (SA), and to investigate whether the effect of CMD on SA is detectable over time. METHOD: Information from a large epidemiological health study (N = 13 436) was linked with official records of SA episodes lasting >=16 days up to 6 years after participation. Common mental disorders were assessed with the Hospital Anxiety and Depression Scale (HADS). Associations were analysed with Cox regression and multinomial logistic regression models controlling for potential covariates. RESULTS: Comorbid anxiety and depression, and anxiety only were significant risk factors for SA after adjusting for covariates, whilst depression only was not. Anxiety and depression were stronger predictors for longer duration of SA episodes compared with shorter duration and associated with more frequent recurrence of SA. There was a general trend toward the effect of CMD on SA becoming weaker over time; however, the effect of anxiety only on SA remained stable throughout the follow-up. CONCLUSION: Common mental disorders are long lasting predictors of onset, duration and recurrence of SA. Anxiety appears to be a more important contributor to long-term SA than previously described in the literature. PMID- 22775342 TI - The association between neurocognitive functioning and smoking in adolescence: the TRAILS study. AB - OBJECTIVE: This study examines the association between neurocognitive functioning and tobacco smoking in adolescence. METHOD: Data from three measurements of the longitudinal Tracking Adolescents' Individual Lives Survey (TRAILS), a large regional population-based cohort study of Dutch adolescents, were used. The first measurement took place in 2001-2002 (T1) when participants were age 11, with two follow-up measurements (2003-2004 and 2005-2007; T2 and T3, respectively). A total of 1,797 adolescents participated in all three waves. At T1, they performed a selection of tasks from the Amsterdam Neuropsychological Tasks program (De Sonneville, 1999), which enabled the assessment of the main aspects of neurocognitive functioning. Smoking was assessed with a self-report questionnaire at T1, T2, and T3. In the multivariate analyses we controlled for gender, age, socioeconomic status (SES) and baseline speed. RESULTS: Multivariate logistic regression analyses showed that poor sustained attention increased the likelihood that the adolescent would initiate smoking between T1 and T2. Low inhibition of prepotent responses increased the likelihood of smoking initiation between T1 and T3. An increased ability to inhibit biased response tendencies reduced the likelihood of being a daily smoker at T2. Poor sustained attention increased the likelihood of being a daily smoker at T3. CONCLUSION: Poor sustained attention and low inhibition predicted adolescent smoking. However, the proportion of the variance in smoking risk accounted for by these neurocognitive predictors proved to be small. Thus, although neurocognitive functioning is related to adolescent smoking, it seems to explain only a small part of why adolescents initiate and continue smoking. PMID- 22775343 TI - Spatial neglect and perseveration in visuomotor exploration. AB - OBJECTIVE: Right-brain-damaged patients with left spatial neglect make perseveration errors in target cancellation tasks. A recent study (Ronchi, Posteraro, Fortis, Bricolo, & Vallar, 2009) showed that perseveration occurred more frequently in star than in letter cancellation, possibly due to different stimulus disposition. In this study we investigated the role of the spatial organization of targets (scattered vs. arranged) of the star and letter cancellation tasks in eliciting omission and perseveration errors; the role of impairments of divided attentional resources; and the lesion correlates of perseveration. METHOD: Thirty-three right-brain-damaged patients (27 with neglect, and six without neglect; 17 showing perseveration, 16 of them with spatial neglect) were given two versions of the star and letter cancellation tasks (with stimuli scattered or in rows), and a dual task. RESULTS: A scattered target disposition increased omission and perseveration errors. Target type modulated differently omission and perseveration, with the former being more elicited by verbal targets, and the latter occurring more frequently in the star cancellation task, with scattered stimuli. Perseveration behavior was unrelated to deficits of divided attention, as assessed by the dual task. Lesion analysis indicated damage to the right insula as a neural correlate of perseveration. CONCLUSIONS: A display including nonverbal (star) and scattered targets brings about more perseveration errors. Target type and organization modulate in a different fashion omission and perseveration, suggesting the involvement of independent pathological mechanisms, which, however, do not implicate deficits of divided attention. The role of insular damage in motor perseveration in spatial neglect is discussed. PMID- 22775345 TI - Development of potent carbonic anhydrase inhibitors incorporating both sulfonamide and sulfamide groups. AB - A series of compounds incorporating both sulfonamide and sulfamide as zinc binding groups (ZBGs) are reported as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Crystallographic studies on the complex of hCA II with the lead compound of this series, namely, 4-sulfamido-benzenesulfonamide, revealed the binding of two molecules in the enzyme active site cavity, the first one canonically coordinated to the zinc ion by means of the sulfonamide group and the second one located at the entrance of the cavity. This observation led to the design of elongated molecules incorporating these two ZBGs, separated by a linker of proper length, to allow the simultaneous binding to these different sites. The "long" inhibitors indeed showed around 10 times better enzyme inhibitory properties as compared to the shorter molecules against four physiologically relevant human (h) isoforms, hCA I, II, IX, and XII. PMID- 22775344 TI - Emotion regulation characteristics and cognitive vulnerabilities interact to predict depressive symptoms in individuals at risk for bipolar disorder: a prospective behavioural high-risk study. AB - Recent work has identified behavioural approach system (BAS) sensitivity as a risk factor for the first onset and recurrence of mood episodes in bipolar disorder, but little work has evaluated risk factors for depression in individuals at risk for, but without a history of, bipolar disorder. The present study evaluated cognitive styles and the emotion-regulatory characteristics of emotional clarity and ruminative brooding as prospective predictors of depressive symptoms in individuals with high versus moderate BAS sensitivity. Three separate regressions indicated that the associations between dysfunctional attitudes, self criticism, and neediness with prospective increases in depressive symptoms were moderated by emotional clarity and brooding. Whereas brooding interacted with these cognitive styles to exacerbate their impact on depressive symptoms, emotional clarity buffered against their negative impact. These interactions were specific to high-BAS individuals for dysfunctional attitudes, but were found across the full sample for self-criticism and neediness. These results indicate that emotion-regulatory characteristics and cognitive styles may work in conjunction to confer risk for and resilience against depression, and that some of these relationships may be specific to individuals at risk for bipolar disorder. PMID- 22775346 TI - Fliposomes: pH-triggered conformational flip of new trans-2-aminocyclohexanol based amphiphiles causes instant cargo release in liposomes. AB - A new type of pH-sensitive liposomes (fliposomes) was designed based on the amphiphiles that are able to perform a pH-triggered conformational flip (flipids). This flip disrupts the liposome membrane and causes rapid release of the liposome cargo, specifically in response to lowered pH. The flipids (1) and (2) are equipped with a trans-2-aminocyclohexanol conformational switch. pH sensitive fliposomes containing one or both of these flipids, as well as POPC and PEG ceramide, were constructed and characterized. These compositions were stable at 4 degrees C and pH 7.4 for several months. Fliposomes loaded with ANTS/DPX performed an unusually quick content release within a few seconds at pH below 8.5 (in case of 2) and 6.0 (in case of 1). This difference in pH sensitivity demonstrates a potential for the custom design of flipids by variation of the amino group to target areas with specific pH values. The pH titration curves for the fliposome leakage parallel the curves for the acid-induced conformational flip of 1 and 2 studied by 1H NMR. A plausible mechanism of pH sensitivity starts with an acid-triggered conformational flip of 1 or 2, which changes the molecular size and shape, shortens the lipid tails, and perturbs the liposome membrane, resulting in the content leakage. PMID- 22775347 TI - Transfusion practice and complications after laparotomy--an observational analysis of a randomized clinical trial. AB - BACKGROUND: Transfusion of allogeneic red blood cells (RBC) may be associated with side effects. This study aimed to assess whether an association could be detected between transfusion practice and the occurrence of complications after laparotomy. STUDY DESIGN AND METHODS: This study is an observational analysis of data from a randomized trial in 1400 patients who underwent laparotomy. A subgroup of 224 transfused patients with an intraoperative blood loss >=200 ml were included in the analysis. Logistic regression analysis was used to investigate risk factors for postoperative complications. The ratio of intraoperative RBC transfusion to blood loss was computed, and patients grouped by the median into a liberal transfusion practice (ratio equal to or above the median) and a restrictive transfusion practice group (ratio below the median). RESULTS: Surgical site infection occurred in 27% of patients in the liberal group vs. 20% of patients in the restrictive group with an OR of 1.5 [95% CI: 0.8-2.9] (P=0.18) and an OR of 1.2 [95% CI: 0.5-2.9] (P=0.73) when adjusting for known confounding variables. Pneumonia occurred in 14% vs. 8% in the liberal and restrictive group, respectively (adjusted P=0.07), and admission to the intensive care unit was 15% vs. 7%, respectively (adjusted P=0.02), but no other significant differences were found. CONCLUSION: A liberal transfusion practice was not significantly associated with postoperative complications, but pneumonia tended to be more common in the liberal group, which was more often admitted to the intensive care unit. PMID- 22775348 TI - Anionic polymerization mechanism of acrylonitrile trimer anions: key branching point between cyclization and chain propagation. AB - A cluster anion of vinyl compounds in the gaseous phase has served as one of the simplest microscopic models of the initial stages of anionic polymerization. Herein, we describe our investigations into the initial stage mechanisms of anionic polymerization of acrylonitrile (AN; CH2?CHCN) trimer anions. While the cyclic oligomer is found in mass and photoelectron spectroscopic studies of (AN)3(-), only the chain oligomer is found in the infrared photodissociation (IRPD) spectrum of Ar-tagged (AN)3(-). On the basis of the calculated polymerization pathway of (AN)3(-), we consider that the chain oligomers are the reaction intermediates in the cyclization of (AN)3(-). The rotational isomerization of the (AN)3(-) chain oligomer is found to be the bottleneck in the cyclization of (AN)3(-). To form the (AN)4(-) chain oligomer by chain propagation, the addition of an AN molecule to (AN)3(-) should occur prior to the rotational isomerization. We conclude that the rotational isomerization in the (AN)3(-) chain oligomer is the key branching point between cyclization (termination) or chain propagation in the anionic polymerization. PMID- 22775350 TI - Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype. AB - The 15q13.3 microdeletion syndrome (OMIM #612001) is characterized by a wide range of phenotypic features, including intellectual disability, seizures, autism, and psychiatric conditions. This deletion is inherited in approximately 75% of cases and has been found in mildly affected and normal parents, consistent with variable expressivity and incomplete penetrance. The common deletion is approximately 2 Mb and contains several genes; however, the gene(s) responsible for the resulting clinical features have not been clearly defined. Recently, four probands were reported with small deletions including only the CHRNA7 gene. These patients showed a wide range of phenotypic features similar to those associated with the larger 15q13.3 microdeletion. To further correlate genotype and phenotype, we queried our database of >15,000 patients tested in the Mayo Clinic Cytogenetics Laboratory from 2008 to 2011 and identified 19 individuals (10 probands and 9 family members) with isolated heterozygous CHRNA7 gene deletions. All but two infants displayed multiple features consistent with 15q13.3 microdeletion syndrome. We also identified the first de novo deletion confined to CHRNA7 as well as the second known case with homozygous deletion of CHRNA7 only. These results provide further evidence implicating CHRNA7 as the gene responsible for the clinical findings associated with 15q13.3 microdeletion. PMID- 22775349 TI - Multivariate analysis of physiological parameters reveals a consistent O3 response pattern in leaves of adult European beech (Fagus sylvatica). AB - * Increasing atmospheric concentrations of phytotoxic ozone (O(3) ) can constrain growth and carbon sink strength of forest trees, potentially exacerbating global radiative forcing. Despite progress in the conceptual understanding of the impact of O(3) on plants, it is still difficult to detect response patterns at the leaf level. * Here, we employed principal component analysis (PCA) to analyse a database containing physiological leaf-level parameters of 60-yr-old Fagus sylvatica (European beech) trees. Data were collected over two climatically contrasting years under ambient and twice-ambient O(3) regimes in a free-air forest environment. * The first principal component (PC1) of the PCA was consistently responsive to O(3) and crown position within the trees over both years. Only a few of the original parameters showed an O(3) effect. PC1 was related to parameters indicative of oxidative stress signalling and changes in carbohydrate metabolism. PC1 correlated with cumulative O(3) uptake over preceding days. * PC1 represents an O(3) -responsive multivariate pattern detectable in the absence of consistently measurable O(3) effects on individual leaf-level parameters. An underlying effect of O(3) on physiological processes is indicated, providing experimental confirmation of theoretical O(3) response patterns suggested previously. PMID- 22775351 TI - Neurodevelopmental investigation of the mirror neurone system in children of women receiving opioid maintenance therapy during pregnancy. AB - AIMS: Opioid maintenance therapy (OMT) is generally recommended for pregnant opioid-dependent women. Previous studies investigating the long-term effects of OMT on children's cognitive development found that children of women in OMT have an increased risk of developing deficits in motor and visual perceptual skills, which are important aspects of the mirror neurone system (MNS), a complex neural circuit involved in learning and social interactions. The aim of the current study was to investigate aspects of the MNS in children of women in OMT. DESIGN: A 2 (control group versus OMT group) * 2 (human versus mechanic) mixed factorial design. SETTING: The Cognitive Developmental Research Unit at the University of Oslo, Norway. PARTICIPANTS: Fifteen children of women in OMT and 15 non-exposed children participated. MEASUREMENTS: Goal-directed eye movements were recorded using a Tobii 1750 eye tracker. Neurocognitive tests were employed to map children's cognitive development. FINDINGS: The OMT group made fewer proactive goal-directed eye movements [mean = -37.73, standard deviation (SD) = 208.56] compared to the control group (mean = 181.47, SD = 228.65), F((1,28)) = 7.53, P = 0.01, eta(2) = 0.21. No differences were found on tests of visual perception or goal understanding. CONCLUSIONS: Use of opioid maintenance therapy during pregnancy appears to be associated with impaired goal-directed eye movements in the 4-year-old infant which may affect later social adjustment adversely. PMID- 22775352 TI - Discriminatory value of signs and symptoms in Cushing's syndrome revisited: what has changed in 30 years? PMID- 22775353 TI - Human mesenchymal stem cells derived from limb bud can differentiate into all three embryonic germ layers lineages. AB - Mesenchymal stem cells (MSCs) have been isolated from many sources, including adults and fetuses. Previous studies have demonstrated that, compared with their adult counterpart, fetal MSCs with several remarkable advantages may be a better resource for clinical applications. In this study, we successfully isolated a rapidly proliferating cell population from limb bud of aborted fetus and termed them "human limb bud-derived mesenchymal stem cells" (hLB-MSCs). Characteristics of their morphology, phenotype, cell cycle, and differentiation properties were analyzed. These adherent cell populations have a typically spindle-shaped morphology. Flow cytometry analysis showed that hLB-MSCs are positive for CD13, CD29, CD90, CD105, and CD106, but negative for CD3, CD4, CD5, CD11b, CD14, CD15, CD34, CD45, CD45RA, and HLA-DR. The detection of cell cycle from different passages indicated that hLB-MSCs have a similar potential for propagation during long culture in vitro. The most novel finding here is that, in addition to their mesodermal differentiation (osteoblasts and adipocytes), hLB-MSCs can also differentiated into extramesenchymal lineages, such as neural (ectoderm) and hepatic (endoderm) progenies. These results indicate that hLB-MSCs have a high level of plasticity and can differentiate into cell lineages from all three embryonic layers in vitro. PMID- 22775355 TI - A sugar beet (Beta vulgaris L.) reference FISH karyotype for chromosome and chromosome-arm identification, integration of genetic linkage groups and analysis of major repeat family distribution. AB - We developed a reference karyotype for B. vulgaris which is applicable to all beet cultivars and provides a consistent numbering of chromosomes and genetic linkage groups. Linkage groups of sugar beet were assigned to physical chromosome arms by FISH (fluorescent in situ hybridization) using a set of 18 genetically anchored BAC (bacterial artificial chromosome) markers. Genetic maps of sugar beet were correlated to chromosome arms, and North-South orientation of linkage groups was established. The FISH karyotype provides a technical platform for genome studies and can be applied for numbering and identification of chromosomes in related wild beet species. The discrimination of all nine chromosomes by BAC probes enabled the study of chromosome-specific distribution of the major repetitive components of sugar beet genome comprising pericentromeric, intercalary and subtelomeric satellites and 18S-5.8S-25S and 5S rRNA gene arrays. We developed a multicolor FISH procedure allowing the identification of all nine sugar beet chromosome pairs in a single hybridization using a pool of satellite DNA probes. Fiber-FISH was applied to analyse five chromosome arms in which the furthermost genetic marker of the linkage group was mapped adjacently to terminal repetitive sequences on pachytene chromosomes. Only on two arms telomere arrays and the markers are physically linked, hence these linkage groups can be considered as terminally closed making the further identification of distal informative markers difficult. The results support genetic mapping by marker localization, the anchoring of contigs and scaffolds for the annotation of the sugar beet genome sequence and the analysis of the chromosomal distribution patterns of major families of repetitive DNA. PMID- 22775356 TI - Membrane inlet mass spectrometer for the quasi-continuous on-site analysis of dissolved gases in groundwater. AB - We developed a stand-alone system based on a membrane inlet mass spectrometer (MIMS) for measuring dissolved gas concentrations in groundwater under field conditions. The system permits the concentrations of dissolved gases (He, Ar, Kr, N(2), and O(2)) in groundwater to be determined quasi-continuously (every 12 min) with a precision of better than 4% for He and Kr, and with a precision of 1% for Ar, N(2), and O(2) in air-saturated water. The detection limits are below 3 * 10( 9) cm(3)(STP)(g) for the noble gases and below 400 * 10(-9)cm(3)(STP)(g) for N(2) and O(2). The results of a first deployment of the system in the field indicate that changes in the concentration of Ar that result from diel fluctuations of 3 degrees C in the river water temperature were still able to be resolved in groundwater, although the corresponding temperature signal almost vanished. PMID- 22775354 TI - Steady-state pharmacokinetics of gabapentin after administration of a novel gastroretentive extended-release formulation in postmenopausal women with vasomotor symptoms. AB - BACKGROUND AND OBJECTIVE: Approximately 75% of postmenopausal women experience vasomotor symptoms (hot flashes). Currently, hormone replacement therapy is the only approved treatment for hot flashes. However, its use has been associated with an increased risk of invasive breast cancer, coronary heart disease, stroke and venous thromboembolic disease. Gabapentin has also been demonstrated to be efficacious in the treatment of vasomotor symptoms in postmenopausal women when administered three times a day. A gastroretentive extended-release formulation of gabapentin (gabapentin-ER) has recently been demonstrated to be efficacious in the treatment of postmenopausal hot flashes. The objective of this paper is to report the steady-state pharmacokinetics and safety of gabapentin with different dosing regimens of gabapentin-ER in postmenopausal women with hot flashes. METHODS: This was a multicentre, randomized, double-blind, dose-escalating, placebo-controlled, parallel group study in 124 postmenopausal women experiencing >=7 moderate to severe hot flashes per day. The study consisted of two 5-week treatment periods, with each one preceded by a 1-week titration to the assigned dose. Groups A, B and C received gabapentin-ER 600 mg evening (pm), 600 mg morning (am)/600 mg pm and 1200 mg pm in the first period, and then 600 mg am/1200 mg pm, 600 mg am/1800 mg pm and 1200 mg am/1800 mg pm in the second period, respectively. The tablets were taken after a non-specified meal. Pharmacokinetic sampling was conducted over a 24-hour period at the end of each study period. Plasma samples were analysed by a validated liquid chromatography tandem mass spectrometry method. Non-compartmental pharmacokinetic analysis was performed on the concentration-time data to determine area under the plasma concentration versus time curve from time zero to 24 hours (AUC(24)). Maximum (C(max)), minimum (C(min)) and average (C(avg)) drug concentration and time to reach C(max) (t(max)) were determined by inspection of the data. Tolerability was evaluated by physical examination, clinical laboratory measurements and adverse events monitoring. RESULTS: Gabapentin exposure at steady state, as measured by AUC(24), increased with doses from 600 mg/day to 3000 mg/day, although there was a slight decrease in gabapentin's relative bioavailability with increasing dose compared with the 600 mg dose. The relative bioavailability compared with the 600 mg dose was 86-88% for the 1200 mg/day doses, 75% for the 1800 mg/day dose, 84% for the 2400 mg/day dose, and 73% for the 3000 mg/day dose. C(max) generally increased with increasing dose as did C(min) and C(avg) for the various treatments in a manner that was consistent with the dosing regimen. The values of t(max) were not different between the various doses, with the median t(max) values relative to the most recent dose ranging from 6 to 8 hours for all dose levels. Gabapentin-ER was generally well tolerated at all doses studied. The most common AEs were headache, dizziness and somnolence, with most being mild in intensity. Seven patients withdrew from the study due to AEs. CONCLUSION: The pharmacokinetic profile of gabapentin-ER may allow for once- or twice-daily dosing while maintaining bioavailability and thus efficacy. Gabapentin-ER was well tolerated. CLINICAL TRIAL REGISTRATION: Registered as ClinicalTrials.gov Identifier: NCT00511953. PMID- 22775357 TI - Transient enhancement of inhibition following visual cortical lesions in the mouse superior colliculus. AB - Numerous studies have investigated the effects of lesions of the primary visual cortex (V1) on visual responses in neurons of the superficial layer of the superior colliculus (sSC), which receives visual information from both the retina and V1. However, little is known about the changes in the local circuit dynamics of the sSC after receiving V1 lesions. Here, we show that surround inhibition of sSC neurons is transiently enhanced following V1 lesions in mice and that this enhancement may be attributed to alterations in the balance between excitatory and inhibitory inputs to sSC neurons. Extracellular recordings in vivo revealed that sSC neuronal responses to large visual stimuli were transiently reduced at about 1 week after visual cortical lesions compared with normal mice and that this reduction was partially recovered at about 1 month after the lesions. By using whole-cell patch-clamp recordings from sSC neurons in slice preparations obtained from mice that had received visual cortical lesions at 1 week prior to the recordings, we found cell type-dependent changes in the balance between excitation and inhibition. In non-GABAergic cells, inhibition predominated over excitation, whereas the excitation-inhibition balance did not change in GABAergic neurons. These results suggest that enhanced inhibition may be partially responsible for the reduced responses to large visual stimuli in some sSC neurons. Thus, we propose that the enhanced surround inhibition shortly after visual cortical lesions may prevent hyperexcitability in the sSC local circuit, contributing to reconstructing the finely tuned receptive field organization of sSC neurons after the visual cortical lesions. PMID- 22775358 TI - Identification of critical steps governing the two-component alkanesulfonate monooxygenase catalytic mechanism. AB - The alkanesulfonate monooxygenase enzyme (SsuD) catalyzes the oxygenolytic cleavage of a carbon-sulfur bond from sulfonated substrates. A mechanism involving acid-base catalysis has been proposed for the desulfonation mechanism by SsuD. In the proposed mechanism, base catalysis is involved in abstracting a proton from the alkane peroxyflavin intermediate, while acid catalysis is needed for the protonation of the FMNO(-) intermediate. The pH profiles of k(cat) indicate that catalysis by SsuD requires a group with a pK(a) of 6.6 +/- 0.2 to be deprotonated and a second group with a pK(a) of 9.5 +/- 0.1 to be protonated. The upper pK(a) value was not present in the pH profiles of k(cat)/K(m). Several conserved amino acid residues (His228, His11, His333, Cys54, and Arg226) have been identified as having potential catalytic importance due to the similar spatial arrangements with close structural and functional relatives of SsuD. Substitutions to these amino acid residues were generated, and the pH dependencies were evaluated and compared to wild-type SsuD. Although a histidine residue was previously proposed to be the active site base, the His variants possessed similar steady-state kinetic parameters as wild-type SsuD. Interestingly, R226A and R226K SsuD variants possessed undetectable activity, and there was no detectable formation of the C4a-(hydro)peroxyflavin intermediate for the Arg226 SsuD variants. Guanidinium rescue with the R226A SsuD variant resulted in the recovery of 1.5% of the wild-type SsuD k(cat) value. These results implicate Arg226 playing a critical role in catalysis and provide essential insights into the mechanistic steps that guide the SsuD desulfonation process. PMID- 22775359 TI - Revealing charge-transfer effects in gas-phase water chemistry. AB - An understanding of the interactions involving water and other small hydrogenated molecules such as H(2)S and NH(3) at the molecular level is an important and elusive scientific goal with potential implications for fields ranging from biochemistry to astrochemistry. One longstanding question about water's intermolecular interactions, and notably hydrogen bonding, is the extent and importance of charge transfer (CT) , which can have important implications for the development of reliable model potentials for water chemistry, among other applications. The weakly bound adducts, commonly regarded as pure van der Waals systems, formed by H(2)O, H(2)S, and NH(3) with noble gases or simple molecules such as H(2), provide an interesting case study for these interactions. Their binding energies are approximately 1 or 2 kJ/mol at most, and CT effects in these systems are thought to be negligible. Our laboratory has performed high resolution molecular-beam scattering experiments that probe the (absolute scale) intermolecular potential of various types of these gas-phase binary complexes with extreme sensitivity. These experiments have yielded surprising and intriguing quantitative results. The key experimental measurable is the "glory" quantum interference shift that shows a systematic, anomalous energy stabilization for the water complexes and clearly points to a significant role for CT effects. To investigate these findings, we have performed very accurate theoretical calculations and devised a simple approach to study the electron displacement that accompanies gas-phase binary intermolecular interactions in extreme detail. These calculations are based on a partial progressive integration of the electron density changes. The results unambiguously show that water's intermolecular interactions are not typical van der Waals complexes. Instead, these interactions possess a definite, strongly stereospecific CT component, even when very weak, where a water molecule may act as electron donor or acceptor depending on its orientation. CT is mediated by an asymmetric role played by the two hydrogen atoms, which causes strong orientation effects. The careful comparison of these calculations with the experimental results shows that the stabilization energy associated to CT is approximately 2-3 eV per electron transferred and may make up for a large portion of the total interaction energy. A simple electron delocalization model helps to validate and explain these findings. PMID- 22775361 TI - An exploratory analysis of aging expectations and health care behavior among aging adults. AB - This study explored the associations between general and specific expectations regarding aging (ERA) and having received a complete physical examination (PE) in the previous 2 years among community-dwelling middle-aged and older adults (M = 70.8 years). Results showed that general-ERA was related to PE after adjusting for covariates (odds ratio = 1.05, p = .04); however, an identical model including the ERA subscales discovered that neither physical- nor cognitive-ERA were related to PE and that mental-ERA was the main independent variable contributing to the association between general-ERA and PE (odds ratio = 1.06, p = .02). Overall, greater scores of general-ERA, but especially mental-ERA, were associated with an increased likelihood of having received a PE in the previous 2 years. PMID- 22775360 TI - Ambivalent versus problematic social ties: implications for psychological health, functional health, and interpersonal coping. AB - Older adults often seek to manage their social networks to foster positive interactions, but they nonetheless sometimes experience negative interactions that detract from their health and well-being. Negative interactions may occur with ambivalent social partners (i.e., partners involved in both positive and negative exchanges) or exclusively problematic social partners (i.e., partners involved in negative exchanges only), but conflicting views exist in the literature regarding which type of social partner is likely to be more detrimental to older adults' physical and emotional health. This study examined the implications of the two kinds of network members for physical and psychological health and interpersonal coping responses in a representative sample of 916 older adults. Analyses revealed that ambivalent social ties were more strongly related to functional health limitations than were exclusively problematic social ties, whereas problematic ties were more consistently related to psychological health than were ambivalent ties. Furthermore, negative exchanges that occurred with exclusively problematic social ties, compared to those that occurred with ambivalent social ties, were associated with more avoidant and fewer conciliatory coping responses, stronger and longer-lasting negative emotions, and lower perceived coping effectiveness. Within this elderly sample, older age was associated with having fewer ambivalent and exclusively problematic kin ties. A comprehensive understanding of the significance of social network ties in older adults' lives may benefit not only from attention to sources of social support but also from efforts to distinguish between different sources of conflict and disappointment. PMID- 22775362 TI - Stability and change in the Big Five personality domains: evidence from a longitudinal study of Australians. AB - Longitudinal data from a nationally representative sample of Australians were used to evaluate mean-level differences and rank-order stability in personality traits assessed twice over a 4-year time span (n = 13,134). Extraversion, Neuroticism, and Openness declined over the life span, whereas Agreeableness increased among young cohorts, was stable among middle-aged cohorts, and declined among the oldest old. Cross-sectional analyses suggested an increase in Conscientiousness throughout the life span, though longitudinal analyses suggested a slight decline in late life. There was an inverted U-shaped pattern for rank-order stability, with peak stability occurring in middle age. For three of the Big Five domains (Extraversion, Agreeableness, and Conscientiousness), age related differences appeared to be somewhat more pronounced before age 30 than after age 30. PMID- 22775363 TI - To predict or not to predict: age-related differences in the use of sentential context. AB - Older adults (as a group) are less likely than younger adults to engage in an anticipatory mode of language comprehension, failing to successfully preactivate information about upcoming likely (predictable) words during online processing. To assess (within one set of materials) age-related changes in the use of sentential context to affect processing of predictable words and in the consequences of violating predictions, event-related brain potentials were recorded while older adults read sentences that varied in sentence-level constraint and expectancy of sentence-final words. Strongly constraining sentences were completed by their most expected, predictable words and weakly constraining sentences were completed by their most expected, less predictable words. Both types of sentences also were completed by unexpected (but plausible) words. Older adults showed reduced and delayed effects of sentential context on processing predictable words. Whereas younger adults elicit an enhanced positive ERP (starting around 500 ms poststimulus onset, largest over prefrontal electrode sites), specifically for unexpected words that violate strong expectancies for a different word, older adults as a group did not exhibit this neural consequence of disconfirmed predictions. Older adults were instead more likely to show a left lateralized frontal negativity for predictable items. This ERP response has been attributed to processes needed to revisit contextual material in forming an interpretation of message-level meaning, which may be more likely when anticipatory modes of comprehension are not engaged. Taken together, the results suggest that normal aging can affect allocation of resources to different cognitive and neural pathways in achieving comprehension outcomes. PMID- 22775364 TI - Mediating processes in an effective life-review intervention. AB - Life review has been established as an evidence-based treatment for depression and anxiety. This paper addresses an important gap in the existing evidence of the working mechanisms of life review. We were able to longitudinally investigate possible mediators of a life-review intervention on depression and anxiety in the context of a large randomized controlled trial. A total of 202 older Dutch adults living in the community participated in this study. They were randomly assigned to either life review or care as usual. Participants were measured in terms of their depressive and anxiety symptoms, reminiscence functions, meaning in life, mastery and positive thoughts at study entry (t0), postintervention (t1; 3 months after study entry), and follow-up (t2; 3 months after the end of the intervention). Findings suggest that processes which have been theoretically and empirically proposed as important processes of change in life review therapy, that is, bitterness revival and boredom reduction reminiscence, mastery and positive thoughts, are indeed mediating the effects of life review on depression and anxiety. It is now recommended to measure these processes during the intervention in order to shed light on the exact process of change and direction of causality. PMID- 22775365 TI - Health is health is health? Age differences in intraindividual variability and in within-person versus between-person factor structures of self-reported health complaints. AB - The variability of health complaints within individuals across time has rarely been studied, and the question whether between- and within-person factor structures of health-related variables are equivalent has not been tested so far. We examined self-reported health complaints in 101 younger (20-31 years) and 103 older adults (65-80 years) over a period of 100 daily assessments. Data were analyzed with confirmatory two-level factor analysis. One-factor structures of health complaints provided an acceptable fit at the between- and average within person levels in both age groups, supporting the assumption of equivalent average within- and between-person factor structures for health complaints. Age differences in loading patterns indicated that subjective health may be experienced differently by younger and older adults. Small age differences in mean levels of health symptoms were observed. Intraindividual variability in health complaints was reliable. Older adults fluctuated less from day to day than younger adults, presumably reflecting less fluctuation in objective health, differences in response styles, situational influences, or habituation processes. We conclude that future research should consider intraindividual variability as being descriptive of a person's health status, and take possible differences between within- and between-person factor structures of subjective health into account. PMID- 22775366 TI - Implications of t'ai chi for smoking cessation. AB - OBJECTIVES: The objective of this study was to identify underlying mechanisms affecting smoking cessation among smokers taking t'ai chi classes. Smokers from t'ai chi classes had attributed t'ai chi practice as the primary reason for quitting smoking. METHODS: Two (2) students from the community college population who had taken a t'ai chi class completed an open-ended questionnaire, to identify possible variables involved in motivations for smoking cessation. An Internet search identified a third student from a university program who had posted observations of how t'ai chi affected her efforts at smoking cessation. The three written responses were evaluated for correlating comments, to identify possible theoretical aspects of why t'ai chi would impact smoking cessation. All three identified increased awareness of smoking habits due to t'ai chi as the primary reason for quitting smoking. A review of literature was conducted to clarify the role of enhanced awareness as a mediator in modifying destructive behavior and addiction. Results from an unpublished study of a t'ai chi smoking cessation program were utilized as supporting data. RESULTS: Two (2) primary areas of behavior modification focusing on the role of enhanced self-awareness are identified from the review of literature: Mindfulness Meditation (MM), and traditional Zen practice. Zen and MM are identified as readily adaptable to using t'ai chi as a form of moving meditation for dealing with addiction. CONCLUSIONS: T'ai chi, as a more dynamic form of meditation, can be an effective method for enhancing mindfulness and awareness for breaking cycles of addiction and habit. Possible effects on physical cravings were also identified. As a novel and unusual form of mind/body exercise, t'ai chi may be a particularly appealing adjunct to smoking cessation programs, particularly in light of the many ancillary health benefits of t'ai chi. PMID- 22775367 TI - Evaluation of a new reusable insulin pen (ClikSTAR) in Canadian patients with type 1 and type 2 diabetes mellitus receiving insulin glargine. AB - BACKGROUND: The objective of this Canadian observational study was to assess the safety and patient satisfaction with the ClikSTAR((r)) (sanofi-aventis, Frankfurt am Main, Germany) reusable insulin pen in clinical practice. SUBJECTS AND METHODS: Patients with diabetes (n=2,517) were recruited from 103 sites, provided with the ClikSTAR pen, and instructed to report product technical complaints (PTCs), product technical failures (PTFs), and adverse events (AEs) over 6-12 weeks of use. A patient subgroup (n = 301) completed a pen use questionnaire at 12 weeks. The risk acceptance criterion was that no validated PTF led to a serious AE (SAE). PTFs were PTCs having a confirmed technical deficiency. RESULTS: Patients (68.5% with type 2 diabetes) had a mean age of 56.2 years, and 92.5% were insulin pen users. In total, 84 PTCs were reported by 79 (3.1%) patients. Most PTCs were due to pen handling errors. PTCs from 12 patients were possibly related to AEs, three of which were SAEs; none was confirmed to be due to a PTF. The single reported PTF was not related to an AE/SAE. In the substudy, 97.0% and 95.3% of patients rated "ease of learning" and "ease of use" of the ClikSTAR pen as excellent or good, respectively. Mean scores for patient satisfaction, convenience, flexibility, and recommendations of current treatment on the Diabetes Treatment Satisfaction Questionnaire (change version) had positive changes ranging from 1.0 to 1.8. CONCLUSIONS: With ClikSTAR, PTCs were infrequent, and there were no PTFs associated with AEs, demonstrating that the pen is reliable and safe with high levels of patient acceptance and satisfaction. PMID- 22775368 TI - Size matters: choosing the right tracheal tube. PMID- 22775369 TI - Wash & go--but with what? Skin antiseptic solutions for central neuraxial block. PMID- 22775370 TI - Extubation guidelines: anaesthetists' experience and confidence. PMID- 22775371 TI - Extubation guidelines: use of airway exchange catheters. PMID- 22775372 TI - Extubation guidelines: Guedel oropharyngeal airways should not be used as bite blocks. PMID- 22775373 TI - Extubation guidelines. PMID- 22775374 TI - Extubation guidelines: management of laryngospasm. PMID- 22775376 TI - Jet ventilator failure. PMID- 22775377 TI - Response from VBM Medizintechnik GmbH. PMID- 22775378 TI - Response from Freelance Surgical Ltd. PMID- 22775379 TI - Satisfaction guaranteed? PMID- 22775380 TI - Ethylene glycol poisoning and the osmolal gap. PMID- 22775382 TI - A complication with an intubating introducer and a double-lumen tube: tip of the iceberg? PMID- 22775383 TI - Epidural volume extension in combined spinal-epidural anaesthesia. PMID- 22775384 TI - The importance of the anaesthetic machine check. PMID- 22775386 TI - EVAR fever. PMID- 22775387 TI - 'Reverse flow' during spinal anaesthesia injections. PMID- 22775388 TI - Recurrent unilateral negative pressure pulmonary oedema. PMID- 22775389 TI - Equivalent air elimination capability does not mean equivalent fluid warming capability. PMID- 22775390 TI - Bladder pain syndrome/interstitial cystitis ESSIC type 3C: high expression of inducible nitric oxide synthase in inflammatory cells. AB - OBJECTIVE: Bladder pain syndrome/interstitial cystitis (BPS/IC) includes a heterogeneous collection of underlying pathological conditions. Compared to the classic IC with a Hunner lesion, now denominated ESSIC type 3C, the non-Hunner type of BPS/IC appears different in a number of respects. In a previous study, measuring luminal nitric oxide (NO) in the bladder of patients with BPS/IC, it was reported that all patients with ESSIC type 3C had high levels of NO. The aim of the present study was to investigate the source of inducible nitric oxide synthase (iNOS) and thereby the cellular origin of NO production via iNOS. MATERIAL AND METHODS: Immunohistochemistry, with two different anti-iNOS antibodies, was used to study 10 patients with BPS/IC ESSIC type 3C who expressed high levels of intraluminal NO. These results were compared with four patients with non-Hunner BPS/IC. To substantiate further the involvement of iNOS in this condition, the protein expression of nitrotyrosine, a marker for iNOS activation, was also assessed. RESULTS: On routine histopathology, the tissues of type 3C patients exhibited inflammatory infiltrates of varying intensity. Strong immunoreactivity for both iNOS and nitrotyrosine was noted within the urothelium but also within the inflammatory infiltrates in the lamina propria of these subjects. CONCLUSIONS: The findings of a clearly detectable protein expression of iNOS in both the urothelium and the inflammatory infiltrates in bladder biopsies from patients with BPS/IC ESSIC type 3C suggest that the production of NO, in this entity, may occur in different tissue compartments. PMID- 22775391 TI - Telomere shortening and karyotypic alterations in hepatocytes in long-term transplanted human liver allografts. AB - The long-term fate of aged liver allografts in young recipients who received grafts from older donors is unknown. We evaluated graft aging by analyzing hepatocytic telomere length and karyotypic changes. Seventeen pediatric individuals who underwent living-donor liver transplantation for congenital biliary diseases were selected. At a median of 10.4 years post-transplant, ten had tolerated grafts with weaned off immunosuppressants, and seven had idiopathic post-transplantation hepatitis. Fluorescence in situ hybridization was used to evaluate the telomere signal intensity (TI) and karyotypic changes. First, we measured predictive age-dependent TI decline with regression analysis of donor livers. The mean TI at the earliest (within a year) and latest biopsies was significantly lower than the predicted TI of the studied allografts. With univariate analysis, a higher abnormal karyotype ratio in the donor liver was correlated with development of idiopathic post-transplantation hepatitis. With multivariate analysis that included clinical parameters, a greater TI decline at the earliest biopsy was correlated with the development of idiopathic post transplantation hepatitis. In conclusion, graft aging as measured by TI decline and donor abnormal karyotype ratio was associated with idiopathic post transplantation hepatitis of long-term transplanted liver allografts. PMID- 22775393 TI - Structure and dynamics of 1-butyl-3-methylimidazolium hexafluorophosphate phases on silica and laponite clay: from liquid to solid behavior. AB - Solid-state NMR experiments show that the behavior of supported 1-butyl-3 methylimidazolium hexafluorophosphate ionic liquid phases depends on the type of support and the phase thickness. A mobile nearly liquid phase is obtained on silica, on the basis of the line widths of the bands in (1)H, (31)P, and (13)C spectra. However, the mobility is somehow restricted, as shown by the possibility of using the cross-polarization technique, although with slow dynamics. On laponite clay, a layered material with a negatively charged surface, a truly solid phase is obtained at low coverage, whereas the increase in ionic liquid loading leads to a second liquid phase, as shown by the presence of two contributions with very different line widths. These two phases seem to coexist without exchange in the NMR time frame. Heteronuclear correlation experiments evidence different relative dispositions of the imidazolium-surface-PF(6) system, with only aromatic protons involved in all the interactions on silica but participation of the benzylic groups (N-CH(3) and/or N-CH(2)) in the case of laponite clay. PMID- 22775392 TI - Response of complex immune-mediated thrombocytopenia to romiplostim in the setting of allogeneic stem cell transplantation for chronic myelogenous leukemia. PMID- 22775394 TI - Anxious ultimatums: how anxiety disorders affect socioeconomic behaviour. AB - Although the role of emotion in socioeconomic decision making is increasingly recognised, the impact of specific emotional disorders, such as anxiety disorders, on these decisions has been surprisingly neglected. Twenty anxious patients and twenty matched controls completed a commonly used socioeconomic task (the Ultimatum Game), in which they had to accept or reject monetary offers from other players. Anxious patients accepted significantly more unfair offers than controls. We discuss the implications of these findings in light of recent models of anxiety, in particular the importance of interpersonal factors and assertiveness in an integrated model of decision making. Finally, we were able to show that pharmacological serotonin used to treat anxious symptomatology tended to normalise decision making, further confirming and extending the role of serotonin in co-operation, prosocial behaviour, and social decision making. These results show, for the first time, a different pattern of socioeconomic behaviour in anxiety disordered patients, in addition to the known memory, attentional and emotional biases that are part of this pathological condition. PMID- 22775395 TI - Platelet transfusions in haematology patients: are we using them appropriately? AB - BACKGROUND AND OBJECTIVES: A large proportion of all platelet components are given to haematology patients. As there are risks associated with their transfusion, costs associated with production, and shortages may occur, it is important that their use is appropriate. STUDY DESIGN AND METHODS: The study was split into two parts, a survey to assess local practice guidelines and an assessment of platelet usage. A total of 123 hospitals completed the survey and 168 hospitals submitted data of 40 haematology patients over a 3-month period. RESULTS: The organizational survey found that 36% of hospitals routinely give prophylactic platelet transfusions to patients with long-term bone-marrow failure. Also, a significant minority of hospitals administer platelet transfusions if the platelet count is below a certain threshold prior to performing a bone-marrow aspirate (11%) or a bone-marrow aspirate and trephine (23%); both of these are contrary to UK platelet transfusion guidelines. Data were collected on a total of 3402 patients, of which 3296 cases were eligible for analysis. They received approximately 46% of all platelet components issued to participating hospitals in England during the study period. The majority (69%) of platelet transfusions were prophylactic; of these only 33% were given when the platelet count was <=10*10(9)/l. Using an algorithm, based on current UK guidelines, 60% of prophylactic transfusions were appropriate, 6% could not be assessed and 34% were inappropriate. A total of 10% of all prophylactic transfusions were double the standard adult dose. CONCLUSIONS: There is considerable potential for decreased use of platelet transfusions with a consequent improvement in their appropriate use and cost reduction. PMID- 22775396 TI - Prolactin signalling in the mouse hypothalamus is primarily mediated by signal transducer and activator of transcription factor 5b but not 5a. AB - Prolactin acts at multiple targets throughout the body, including the mammary gland, heart, liver, muscle and brain. Upon binding to its receptors, prolactin signals through the phosphorylation and thus activation of signal transducer and activator of transcription 5 (STAT5). There are two very similar STAT5 isoforms, termed STAT5a and STAT5b, which are selectively activated by prolactin in specific tissues. Various brain regions, including the hypothalamus, are prolactin responsive, although the STAT5 isoform involved in these actions is unknown. Immunohistochemical and western blot analysis were used to determine the expression and activation of STAT5a and STAT5b throughout the hypothalamus in adult wild-type and STAT5b-deficient mice. Both groups were pretreated with bromocriptine to suppress endogenous prolactin levels followed by the administration of ovine prolactin (10 mg/kg) for 45 min. STAT5a and STAT5b were expressed throughout the hypothalamus of wild-type mice. As expected, only STAT5a was detected in STAT5b-deficient mice, although, unexpectedly, there was a marked reduction in its expression compared to wild-type mice. When stimulated with prolactin, phosphorylated STAT5 was observed in the hypothalamus of wild-type but not STAT5b-deficient mice. By contrast, phosphorylated STAT5 was detected in mammary gland epithelial cells and adipocytes of STAT5b-deficient animals. Thus, although STAT5a was still expressed in the STAT5b-deficient mice, it was not phosphorylated in the hypothalamus in response to prolactin. These observations indicate that STAT5b but not STAT5a is the primary mediator of the action of prolactin in the hypothalamus. Despite the similarity between the two STAT5 isoforms, STAT5a was unable to compensate for the absence of STAT5b, suggesting that each isoform exhibits a unique biological activity. PMID- 22775397 TI - 6-Trifluoromethylpyridoxine: novel (19)F NMR pH indicator for in vivo detection. AB - pH plays an important role in tumor proliferation, angiogenesis, metabolic control, and the efficacy of cytotoxic therapy, and accurate noninvasive assessment of tumor pH promises to provide insight into developmental processes and prognostic information. In this paper, we report the design, synthesis, and characterization of two novel pH indicators 6-trifluoromethylpyridoxine 8 and alpha(4),alpha(5)-di-O-[3'-O-(beta-d-glucopyranosyl)propyl]-6 trifluoromethylpyridoxine 17 and demonstrate 8 as an extracellular (19)F NMR pH probe to assess pH(e) of various tumors in vivo. PMID- 22775398 TI - Chinese patients with Huntington's disease initially presenting with spinocerebellar ataxia. AB - Recent studies have described Huntington's disease (HD) patients with atypical onset of ataxia. Symptoms in these patients can overlap with those of spinocerebellar ataxia (SCA). We retrospectively examined clinical data for 82 HD probands and found 7 had initially been clinically diagnosed as SCA cases. Clinical features in these patients were further investigated and the number of CAG repeats in the huntingtin (HTT) gene was determined by direct sequencing. Genetic screenings for SCAs in the 7 patients were all negative. By contrast, HTT was heterozygous in each patient. The distribution of CAG number in the 7 patients was statistically the same as that in the other 75 patients. Each of 7 HD patients had presented with atypical onset of ataxia. The mean time from onset to HTT genetic testing was 5.6 +/- 5.52 years. Three of the patients developed chorea, but the others did not. Our observations confirm the clinical heterogeneity of HD in Han Chinese. Based on these findings, testing for HTT expansions should be considered for clinically diagnosed SCA patients who test negatively in genetic screening of SCA genes. PMID- 22775399 TI - Separation of early and late responses to herbivory in Arabidopsis by changing plasmodesmal function. AB - Herbivory results in an array of physiological changes in the host that are separable from the associated physical damage. We have made the surprising observation that an Arabidopsis line (pdko3) mutated in genes encoding plasmodesmal proteins is defective in some, but not all, of the typical plant responses to herbivory. We tested the responses of plasma transmembrane potential (Vm) depolarization, voltage gated K(+) channel activity, cytosolic calcium [Ca2+]cyt and reactive oxygen species (ROS) (H2 O2 and NO) release, shoot-to-root signaling, biosynthesis of the phytohormone jasmonic acid (JA) and the elicitation of volatile organic compounds (VOCs). Following herbivory and the release of factors present in insect oral secretions (including a putative beta galactofuranose polysaccharide), both the pdko3 and wild type (WT) plants showed a increased accumulation of [Ca2+]cyt , NO and H2 O2 . In contrast, unlike WT plants, the mutant line showed an almost complete loss of voltage gated K(+) channel activity and Vm depolarization, a loss of shoot-induced root-Vm depolarization, a loss of activation and regulation of gene expression of the JA defense pathway, and a much diminished release and altered profile of VOCs. The mutations in genes for plasmodesmal proteins have provided valuable genetic tools for the dissection of the complex spectrum of responses to herbivory and shown us that the responses to herbivory can be separated into a calcium-activated oxidative response and a K(+) -dependent Vm-activated jasmonate response associated with the release of VOCs. PMID- 22775401 TI - Modeling environmental impacts of urban expansion: a systematic method for dealing with uncertainties. AB - In a rapidly transitioning China, urban land use has changed dramatically, both spatially and in terms of magnitude; these changes have significantly affected the natural environment. This paper reports the development of an Integrated Environmental Assessment of Urban Land Use Change (IEA-ULUC) model, which combines cellular automata, scenario analysis, and stochastic spatial sampling with the goal of exploring urban land-use change, related environmental impacts, and various uncertainties. By applying the IEA-ULUC model to a new urban development area in Dalian in northeastern China, the evolution of spatial patterns from 1986 to 2005 was examined to identify key driving forces affecting the changing trajectories of local land use. Using these results, future urban land use in the period 2005-2020 was projected for four scenarios of economic development and land-use planning regulation. A stochastic sampling process was implemented to generate industrial land distributions for each land expansion scenario. Finally, domestic and industrial water pollution loads to the ocean were estimated, and the environmental impacts of each scenario are discussed. The results showed that the four urban expansion scenarios could lead to considerable differences in environmental responses. In principle, urban expansion scenarios along the intercity transportation rail/roadways could have higher negative environmental impacts than cluster-developing scenarios, while faster economic growth could more intensely aggravate the environment than in the moderate growth scenarios. PMID- 22775400 TI - Obestatin does not modify weight and nutritional behaviour but is associated with metabolic syndrome in old women. AB - OBJECTIVE: Ghrelin and obestatin have apparent opposite orexigenic and anorexigenic effects, although the latter has not been firmly demonstrated in humans. So far, little data have been reported in relation to its potential association with metabolic syndrome (MS). The objective was to study obestatin concentrations in relation to nutritional parameters and eating behaviours in old women. DESIGN, PATIENTS AND MEASUREMENTS: Prospective study; a total of 110 women (age: 76.93 +/- 6.32) from the Mataro Ageing Study were included. Individuals were characterized by anthropometric variables, lipids, glucose, blood pressure, MS components (Adult Treatment Panel III criteria), anorexia and nutritional status by Mini Nutritional Assessment Short Form (MNA-SF) and re-evaluated at 2 year follow-up. Obestatin was measured by IRMA. RESULTS: 58.2% of the subjects had MS; at 2-year follow-up 24.1% had a weight loss >5%, 7.2% >10%, and 26.4% changed their MNA-SF score to risk of malnutrition category. Anorexia was present in 38.4%. Obestatin levels were not related to either change of weight, MNA-SF or anorexia, but a positive correlation was found with the absolute difference between basal and 2-year waist circumference (WC) (r = 0.429; P < 0.001) and relative difference between basal and 2-year WC (r = 0.420; P < 0.001); both remained significant after adjusting for age and body mass index. When obestatin was divided into quartiles, a significant lineal trend was observed in relation to WC (P = 0.049), absolute and relative difference between basal and 2-year WC (both P < 0.001). Obestatin was associated with glucose impairment (69.0% in 4th quartile vs 47.5% in 1st to 3rd, P = 0.047; after adjustment, P = 0.098) and MS (77.8% in 4th vs 51.3% in 1st to 3rd, P = 0.017; after adjustment, P = 0.046, OR 2.90 (1.02-8.25) 4th vs 1st to 3rd). CONCLUSIONS: Obestatin is elevated in aged women bearing MS but is otherwise not associated with other nutritional parameters, weight loss or anorexia. PMID- 22775402 TI - Introduction to the Symposium-in-Print: 21st Conference of the Inter-American Photochemical Society, Mendoza, Argentina, May 2011. PMID- 22775403 TI - Crystal structures of substrate-free and nitrosyl cytochrome P450cin: implications for O(2) activation. AB - The crystal structure of the P450cin substrate-bound nitric oxide complex and the substrate-free form have been determined revealing a substrate-free structure that adopts an open conformation relative to the substrate-bound structure. The region of the I helix that forms part of the O(2) binding pocket shifts from an alpha helix in the substrate-free form to a pi helix in the substrate-bound form. Unique to P450cin is an active site residue, Asn242, in the I helix that H-bonds with the substrate. In most other P450s this residue is a Thr and plays an important role in O(2) activation by participating in an H-bonding network required for O(2) activation. The pi/alpha I helix transition results in the carbonyl O atom of Gly238 moving in to form an H-bond with the water/hydroxide ligand in the substrate-free form. The corresponding residue, Gly248, in the substrate-free P450cam structure experiences a similar motion. Most significantly, in the oxy-P450cam complex Gly248 adopts a position midway between the substrate-free and -bound states. A comparison between these P450cam and the new P450cin structures provides insights into differences in how the two P450s activate O(2). The structure of P450cin complexed with nitric oxide, a close mimic of the O(2) complex, shows that Gly238 is likely to form tighter interactions with ligands than the corresponding Gly248 in P450cam. Having a close interaction between an H-bond acceptor, the Gly238 carbonyl O atom, and the distal oxygen atom of O(2) will promote protonation and hence further reduction of the oxy complex to the hydroperoxy intermediate resulting in heterolytic cleavage of the peroxide O-O bond and formation of the active ferryl intermediate required for substrate hydroxylation. PMID- 22775404 TI - A crossover comparison of glycemic variations in Japanese patients with type 1 diabetes receiving insulin glargine versus insulin detemir twice daily using continuous glucose monitoring (CGM): J COLLECTION (Jikei COmparison of Lantus and LEvemir with Cgm for Thinking Insulin OptimizatioN). AB - BACKGROUND: This study aimed to compare glycemic variations seen among Japanese patients with type 1 diabetes treated with insulin glargine versus insulin detemir using continuous glucose monitoring (CGM) in a crossover design. SUBJECTS AND METHODS: Twenty-three patients with type 1 diabetes were enrolled in this study. The subjects were on either insulin glargine followed by insulin detemir twice daily, or vice versa, with no change in the timing of injections. The glycemic variations during 4-day hospitalizations were monitored by CGM while the patients were on either regimen, with a second hospitalization scheduled more than 1 month after the change of the long-acting insulin analogs. CGM data obtained on Day 3 of both hospitalizations were compared. RESULTS: The subjects had a median age of 44.0 years, a median body mass index of 22.2 kg/m(2), and a median glycosylated hemoglobin of 7.3%. There was no significant difference between the two treatments with a mean glucose level of 156 mg/dL with the insulin glargine treatment versus 150 mg/dL with the insulin detemir treatment; their SD values were 60 versus 51 mg/dL, their mean amplitude of glycemic excursions values were 121 versus 105 mg/dL, and their mean of daily differences values were 45.7 versus 41.4 mg/dL, respectively. In addition, the insulin detemir treatment was associated with a narrower range of postprandial glucose increases after lunch (80 vs. 59 mg/dL; P=0.007). CONCLUSIONS: A comparison of the long-acting insulin analogs administered twice daily in type 1 diabetes demonstrated that insulin detemir may potentially offer better glycemic control after lunch than insulin glargine. PMID- 22775405 TI - What constitutes uncertainty in systemic lupus erythematosus and rheumatoid arthritis? AB - Patient uncertainty is associated with conditions with no known cause or cure, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and despite its potential role in chronic illness management, it is still a poorly understood concept. This study constitutes an in-depth investigation of patient uncertainty in SLE and RA. We conducted (i) structured interviews with a sample of rheumatology health care professionals (HCPs) (n = 8) and (ii) in-depth, semi structured interviews with a sample of SLE (n = 17) and RA (n = 15) patients. Interviews were audio-taped, transcribed verbatim and analysed thematically using detailed line-by-line coding. Patient uncertainty was conceptualised in a framework of five domains: symptoms and prognosis, medical management, self management, impact and social functioning. Even though these five domains were present in both the SLE and RA data, there were some differences at the sub domain level. Several sources of uncertainty were put forward by the HCPs and subsequently confirmed in the patient interviews including the illness trajectory, age, gender and timing. Patients reported uncertainty relative to various aspects of their illness, its management and impact. Finally, HCPs discussed the behavioural and psychosocial impact of uncertainty, which further suggests its important role in patient management. PMID- 22775407 TI - Clonal chromosome anomalies affecting FLI1 mimic inherited thrombocytopenia of the Paris-Trousseau type. AB - INTRODUCTION: The thrombocytopenia of the Paris-Trousseau (TCPT) type is a contiguous gene syndrome characterized by mild bleeding tendency, variable thrombocytopenia (THC), abnormal giant alpha-granules in platelets and dysmegakaryopoiesis: it derives from a constitutional deletion of chromosome 11 leading to the loss of FLI1, a transcription factor involved in megakaryocyte differentiation and maturation. CASE REPORT: A women with an acquired, isolated THC developing over 10 yr showed morphological features typical of TCPT in platelets and bone marrow (BM). Twenty years after the onset of THC, the other hematological parameters are still normal and the patient is well. RESULTS: Clonal hemopoiesis was shown and chromosome analyses performed on BM revealed a clone with 45 chromosomes and a complex unbalanced translocation involving chromosomes 2, 3, and 11. The anomaly was present in the majority of bone marrow cells but only in a few peripheral blood elements. A microarray-based comparative genomic hybridization defined the deleted region of chromosome 11 including the FLI1 locus that was missing. CONCLUSION: Although our patient presented with nearly all the characteristics of TCPT, her illness was acquired instead of being inherited and the most appropriate diagnosis is that of the unilineage dysplasia 'refractory THC.' This observation suggests that appropriate cytogenetic investigations should be always considered in patients with acquired THC of unknown origin. PMID- 22775406 TI - Effects of independent and substance-induced major depressive disorder on remission and relapse of alcohol, cocaine and heroin dependence. AB - AIMS: Little is known about the differential effects of independent and substance induced major depression on the longitudinal course of alcohol, cocaine and heroin disorders when studied prospectively. DESIGN: Consecutively admitted in patients, evaluated at baseline, 6-, 12- and 18-month follow-ups. SETTING: Baseline evaluations in a short-stay in-patient urban community psychiatric hospital unit. PARTICIPANTS: Adults (n = 250) with current DSM-IV cocaine, heroin and/or alcohol dependence at baseline. MEASUREMENTS: The Psychiatric Research Interview for Substance and Mental Disorders (PRISM), used to evaluate independent and substance-induced major depression, alcohol, cocaine and heroin dependence, and other psychiatric disorders. Outcomes for each substance: (i) time (weeks) from hospital discharge to first use; (ii) time from discharge to onset of sustained (>=26 weeks) remission from dependence; (iii) time from onset of sustained remission to relapse. FINDINGS: Substance-induced major depression significantly predicted post-discharge use of alcohol, cocaine and heroin (hazard ratios 4.7, 5.3 and 6.5, respectively). Among patients achieving stable remissions from dependence, independent major depression predicted relapse to alcohol and cocaine dependence (hazard ratios 2.3 and 2.7, respectively). CONCLUSIONS: Substance-induced and independent major depressions were both related to post-discharge use of alcohol, cocaine and heroin. The findings suggest the importance of clinical attention to both types of depression in substance abusing patients. PMID- 22775408 TI - The psychometric properties of the Inventory of Callous-Unemotional Traits in an undergraduate sample. AB - In the present study, the psychometric properties and factor structure of the 24 item Inventory of Callous-Unemotional Traits (ICU) were tested in a sample of 687 college students. Results support a similar 3-factor structure to that identified in samples of youths, in whom this measure was previously validated. Correlations with external variables support the convergent and discriminant validity of the ICU total score and Uncaring and Callousness factor scores. The ICU was moderately to strongly correlated with the total score and the Coldheartedness and Self-Centered Impulsivity factors of the Psychopathic Personality Inventory Revised, and the total score of Levenson's Self-Report Psychopathy Scale, and also predicted incremental variance in several external variables beyond these existing self-report psychopathy measures. Together, these findings suggest that with a few modifications, the ICU may hold promise as a brief self-report measure for assessing traits reflecting callousness and "meanness" in adults. High scores identified college students who tended to show antisocial tendencies consistent with diagnostic criteria for antisocial personality disorder, while also exhibiting low levels of empathy. Recommendations for future research with the ICU are discussed. PMID- 22775409 TI - Factor structure of the B-Scan 360: a measure of corporate psychopathy. AB - Psychopathy is a clinical construct defined by a cluster of personality traits and behaviors, including grandiosity, egocentricity, deceptiveness, shallow emotions, lack of empathy or remorse, irresponsibility, impulsivity, and a tendency to ignore or violate social norms. The majority of empirical research on psychopathy involves forensic populations most commonly assessed with the Psychopathy Checklist-Revised (PCL-R), a 20-item rating scale that measures 4 related factors or dimensions (Interpersonal, Affective, Lifestyle, and Antisocial) that underpin the superordinate construct of psychopathy. Recently, researchers have turned their attention to the nature and implications of psychopathic features in the workplace. This research has been hampered by the lack of an assessment tool geared to the corporate/organizational world. Here we describe the B-Scan 360, an instrument that uses ratings of others to measure psychopathic features in workplace settings. In this study, large samples of participants used an online survey system to rate their supervisors on the B-Scan 360. Exploratory and confirmatory factor analyses supported a reliable 20-item, 4 factor model that is consistent with the PCL-R 4-factor model of psychopathy. Although more research is needed before the B-Scan 360 can be used in organizational settings, we believe that these results represent an important step forward in the study of corporate psychopathy. PMID- 22775410 TI - Internal structure of the Reflective Functioning Scale. AB - The Reflective Functioning Scale (RFS) was developed to assess individual differences in the ability to mentalize attachment relationships. The RFS assesses mentalization from transcripts of the Adult Attachment Interview (AAI). A global score is given by trained coders on an 11-point scale ranging from antireflective to exceptionally reflective. Coding procedures rely on a distinction of demand and permit questions during the AAI. Demand questions directly probe for reflective functioning (RF), whereas permit questions do not. Coding focuses on detecting qualitative markers of RF and qualitative markers of absent RF, respectively. Despite its relevant empirical contributions in clinical research, several psychometric properties of the RFS are still unclear. In this article, we present data on the reliability and internal structure of the RFS based on a combined sample of 196 subjects. We were able to show that (a) the global score can be assessed with good interrater reliability, is relatively stable across time, and is significantly reduced in persons with mental disorders; (b) demand questions are based on a single latent factor; (c) demand questions do not differ in terms of difficulty; (d) all demand questions but 1 are incrementally predictive of the global score; (e) 5 permit questions contribute to the global score over and above demand questions; and (f) the number of qualitative markers of RF is also predictive of the global score. Our results have important conceptual and methodological implications for future studies using the RFS. PMID- 22775411 TI - Recombinant rabbit leukemia inhibitory factor and rabbit embryonic fibroblasts support the derivation and maintenance of rabbit embryonic stem cells. AB - The rabbit is a classical experimental animal species. A major limitation in using rabbits for biomedical research is the lack of germ-line-competent rabbit embryonic stem cells (rbESCs). We hypothesized that the use of homologous feeder cells and recombinant rabbit leukemia inhibitory factor (rbLIF) might improve the chance in deriving germ-line-competent rbES cells. In the present study, we established rabbit embryonic fibroblast (REF) feeder layers and synthesized recombinant rbLIF. We derived a total of seven putative rbESC lines, of which two lines (M5 and M23) were from culture Condition I using mouse embryonic fibroblasts (MEFs) as feeders supplemented with human LIF (hLIF) (MEF+hLIF). Another five lines (R4, R9, R15, R21, and R31) were derived from Condition II using REFs as feeder cells supplemented with rbLIF (REF+rbLIF). Similar derivation efficiency was observed between these two conditions (8.7% vs. 10.2%). In a separate experiment with 2*3 factorial design, we examined the effects of feeder cells (MEF vs. REF) and LIFs (mLIF, hLIF vs. rbLIF) on rbESC culture. Both Conditions I and II supported satisfactory rbESC culture, with similar or better population doubling time and colony-forming efficiency than other combinations of feeder cells with LIFs. Rabbit ESCs derived and maintained on both conditions displayed typical ESC characteristics, including ESC pluripotency marker expression (AP, Oct4, Sox2, Nanog, and SSEA4) and gene expression (Oct4, Sox2, Nanog, c-Myc, Klf4, and Dppa5), and the capacity to differentiate into three primary germ layers in vitro. The present work is the first attempt to establish rbESC lines using homologous feeder cells and recombinant rbLIF, by which the rbESCs were derived and maintained normally. These cell lines are unique resources and may facilitate the derivation of germ-line-competent rbESCs. PMID- 22775413 TI - Convective rolls and hydrothermal waves in evaporating sessile drops. AB - Recent experiments on the evaporation of sessile droplets have revealed the spontaneous formation of various patterns including the presence of hydrothermal waves. These waves had previously been observed, in the absence of evaporation, in thin liquid layers subjected to an imposed, uniform temperature gradient. This is in contrast to the evaporating droplet case wherein these gradients arise naturally due to evaporation and are spatially and temporally varying. In the present paper, we present a theory of evaporating sessile droplets deposited on a heated surface and propose a candidate mechanism for the observed pattern formation using a linear stability analysis in the quasi-steady-state approximation. A qualitative agreement with experimental trends is observed. PMID- 22775412 TI - Diabetes mellitus reduces the clearance of atorvastatin lactone: results of a population pharmacokinetic analysis in renal transplant recipients and in vitro studies using human liver microsomes. AB - BACKGROUND AND OBJECTIVE: Patients with diabetes mellitus might be at a higher risk of HMG-CoA reductase inhibitor (statin)-induced myotoxicity, possibly because of reduced clearance of the statin lactone. The present study was designed to investigate the effect of diabetes on the biotransformation of atorvastatin acid, both in vivo in nondiabetic and diabetic renal transplant recipients, and in vitro in human liver samples from nondiabetic and diabetic donors. SUBJECTS AND METHODS: A total of 312 plasma concentrations of atorvastatin acid and atorvastatin lactone, from 20 nondiabetic and 32 diabetic renal transplant recipients, were included in the analysis. Nonlinear mixed effects modelling was employed to determine the population pharmacokinetic estimates for atorvastatin acid and atorvastatin lactone. In addition, the biotransformation of these compounds was studied using human liver microsomal fractions obtained from 12 nondiabetic and 12 diabetic donors. RESULTS: In diabetic patients, the plasma concentration of atorvastatin lactone was significantly higher than that of atorvastatin acid throughout the 24-hour sampling period. The optimal population pharmacokinetic model for atorvastatin acid and atorvastatin lactone consisted of a two- and one-compartment model, respectively, with interconversion between atorvastatin acid and atorvastatin lactone. Parent drug was absorbed orally with a population estimate first-order absorption rate constant of 0.457 h(-1). The population estimates of apparent oral clearance (CL/F) of atorvastatin acid to atorvastatin lactone, intercompartmental clearance (Q/F), apparent central compartment volume of distribution after oral administration (V(1)/F) and apparent peripheral compartment volume of distribution after oral administration (V(2)/F) for atorvastatin acid were 231 L/h, 315 L/h, 325 L and 4910 L, respectively. The population estimates of apparent total clearance of atorvastatin lactone (CL(M)/F), apparent intercompartmental clearance of atorvastatin lactone (Q(M)/F) and apparent volume of distribution of atorvastatin lactone after oral administration (V(M)/F) were 85.4 L/h, 166 L/h and 249 L, respectively. The final covariate model indicated that the liver enzyme lactate dehydrogenase was related to CL/F and alanine aminotransferase (ALT) was related to Q/F. Importantly, diabetic patients have 3.56 times lower CL(M)/F than nondiabetic patients, indicating significantly lower clearance of atorvastatin lactone in these patients. Moreover, in a multivariate population pharmacokinetics model, diabetes status was the only significant covariate predicting the values of the CL(M)/F. Correspondingly, the concentration of atorvastatin acid remaining in the microsomal incubation was not significantly different between nondiabetic and diabetic liver samples, whereas the concentration of atorvastatin lactone was significantly higher in the samples from diabetic donors. In vitro studies, using recombinant enzymes, revealed that cytochrome P450 (CYP) 3A4 is the major CYP enzyme responsible for the biotransformation of atorvastatin lactone. CONCLUSIONS: These studies provide compelling evidence that the clearance of atorvastatin lactone is significantly reduced by diabetes, which leads to an increased concentration of this metabolite. This finding can be clinically valuable for diabetic transplant recipients who have additional co-morbidities and are on multiple medications. PMID- 22775414 TI - Antioxidative and cardiovascular-protective activities of metabolite usnic acid and psoromic acid produced by lichen species Usnea complanata under submerged fermentation. AB - CONTEXT: Lichens have been used for various purposes such as dyes, perfumes and remedies in folk medicine indicating the pharmaceutical potential of lichens. OBJECTIVE: Lichen growth in nature is very slow. To overcome this major drawback, we standardized the culture media to culture the lichen Usnea complanata (Mull.Arg.) Motyka (Parmeliaceae) for (1) in vitro synthesis of natural lichen substances, and (2) determination of antioxidative and cardiovascular-protective activity of usnic acid and psoromic acid. MATERIALS AND METHODS: Lichen U. complanata has been cultured in fermentor under submerged condition. Antioxidative and cardiovascular-protective activity of the extract and the purified lichen substances usnic and psoromic acid have been determined. RESULTS: Except methanol, all other extracts exhibited antioxidative action in terms of free radical scavenging activity (FRSA) with a half-inhibiting concentration (IC50) value of 22.86 to 25.0 ug/mL, nitric oxide radical scavenging activity (NORSA) 141.3 to 149.1 ug/mL and for lipid peroxidation inhibition (LPI) 125 to 157.9 ug/mL. Usnic acid or psoromic acid showed antioxidative action with IC50 values ranging from 0.174 to 0.271 mg/mL. Methanol and ethyl acetate extract showed hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) inhibition of 65.18 to 74.81%. Only 43.47% inhibition of angiotensin converting enzyme (ACE) was shown by methanol extract. Usnic acid showed noncompetitive type of HMGR inhibition and uncompetitive type of ACE inhibition. Psoromic acid exhibited competitive type of HMGR inhibition and mixed type of ACE inhibition. DISCUSSION: U. complanata showed both cardiovascular-protective and antioxidant properties. The lichen species U. complanata may be a natural bioresource for possible pharmaceutical applications. PMID- 22775415 TI - Involvement of intrinsic mitochondrial pathway in neosergeolide-induced apoptosis of human HL-60 leukemia cells: the role of mitochondrial permeability transition pore and DNA damage. AB - CONTEXT: Quassinoids are biologically active secondary metabolites found exclusively in the Simaroubaceae family of plants. These compounds generally present important biological properties, including cytotoxic and antitumor properties. OBJECTIVE: In the present study, the cytotoxic effects of neosergeolide, a quassinoid isolated from Picrolemma sprucei Hook. f., were evaluated in human promyelocytic leukemia cells (HL-60). MATERIALS AND METHODS: Cytotoxicity and antiproliferative effects were evaluated by the MTT assay, May Grunwald-Giemsa's staining, BrdU incorporation test, and flow cytometry procedures. The comet assay and micronuclei analysis were applied to determine the genotoxic and mutagenic potential of neosergeolide. RESULTS: After 24 h exposure, neosergeolide strongly inhibited cancer cell proliferation (IC50 0.1 uM), and its activity seemed to be selective to tumor cells because it had no antiproliferative effect on human peripheral blood mononuclear cells (PBMC) at tested concentrations. Apoptosis was induced at submicromolar concentrations (0.05, 0.1, and 0.2 uM) as evidenced by morphological changes, mitochondrial depolarization, phosphatidylserine externalization, caspases activation, and internucleosomal DNA fragmentation. Additionally, neosergeolide effects were prevented by cyclosporine A (CsA), an inhibitor of the mitochondrial permeability transition (MPT) pore, which reinforced the participation of intrinsic pathways in the apoptotic process induced by this natural quassinoid. Direct DNA damage was further confirmed by comet assay and cytokinesis-block micronucleus test. DISCUSSION AND CONCLUSION: The present study provided experimental evidence to support the underlying mechanism of action involved in the neosergeolide-mediated apoptosis. In addition, no antiproliferative effect or DNA damage effect of neosergeolide was evident in PBMC, highlighting its therapeutic potential. PMID- 22775416 TI - Sub-chronic toxicity study of the methanol root extract of Cnestis ferruginea. AB - CONTEXT: Cnestis ferruginea (CF) Vahl ex DC (Connaraceae) is a shrub abundant in West Africa. Root preparations are used in traditional medicine to treat diverse conditions. OBJECTIVE: To evaluate the sub-chronic toxicological effects of the methanol root extract of CF. MATERIALS AND METHODS: Groups of adult rats of both sexes were treated daily with distilled water (DW) and CF at doses of 80 (sub therapeutic dose), 400 (therapeutic dose), and 1000 (supra-therapeutic dose) mg/kg orally for 90 days. Animals were weighed weekly and observed for behavioral and morphological changes. At the end, rats were sacrificed and blood samples collected for hematological and biochemical analysis. Vital organs were harvested, weighed, and assessed for in vivo antioxidants and histopathological changes. Sperm analysis and reversibility study were done, and mortality was recorded. RESULTS: CF at the therapeutic dose did not produce any significant irreversible deleterious effects on the weight of animals and vital organs, in vivo antioxidants, histopathological presentation, hematological, biochemical, and sperm parameters. Platelet anomaly was elicited as a delayed effect. Effects at the sub- and supra-therapeutic doses were similar but with delayed anemia in females and weight reduction and sterility in males as possible side effects. CF generally showed a potential to induce in vivo antioxidants. DISCUSSION AND CONCLUSION: Findings suggest that CF given over an extended period possess the potential to cause induction of in vivo antioxidants especially in the ovary. Possible side effects identified with CF, which necessitate caution, include delayed platelet anomaly and anemia in females, weight reduction, and sterility in males. PMID- 22775417 TI - Alteration of hepatic glutathione peroxidase and superoxide dismutase expression in streptozotocin-induced diabetic mice by berberine. AB - CONTEXT: Diabetes mellitus (DM), a chronic disease, has been increasing and subsequently devastates the quality of life and economic status of the patients. Oxidative stress participates in development and progression of diabetes, in which levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were changed in diabetic mice. Berberine has been widely used as an alternative medicine and proved to be effective for treatment of DM and dyslipidemia. OBJECTIVE: Impacts of berberine on regulation of GPx and SOD messenger RNAs (mRNAs), and glutathione (GSH) content were examined in diabetic mice to clarify its antioxidative stress potential. MATERIALS AND METHODS: Noninsulin-dependent diabetes was induced in mice by a single intraperitoneal streptozotocin injection. Diabetic mice were daily treated with metformin (100 mg/kg/d) or berberine (200 mg/kg/d) for 2 weeks. The fasting blood glucose and GSH content were monitored. GPx and SOD mRNA expression were semi-quantified by reverse transcription-polymerase chain reaction. RESULTS: Berberine showed the same hypoglycemic potential as metformin, a hypoglycemic drug. Interestingly, berberine did not change levels of GPx, copper-zinc SOD (CuZn-SOD), and manganese SOD (Mn-SOD) mRNA in the normal mice but significantly recovered these levels in the diabetic mice to nearly the same levels as the normal. The GSH contents, including total GSH and reduced/oxidized GSH contents, were restored to the normal level by berberine, corresponded to GPx levels. DISCUSSION AND CONCLUSION: Berberine conveyed antioxidative effect via down- and up-regulation of GPx and CuZn-SOD expression, respectively. Therefore, use of berberine as a hypoglycemic compound for alternative treatment of DM could bring extra-beneficent consequence according to its antioxidative stress. PMID- 22775418 TI - Antioxidant and cytotoxic potential of a new thienyl derivative from Tagetes erecta roots. AB - CONTEXT: The search for newer compounds against pathogenic species continues unabated due to drug resistance. Traditionally, Tagetes erecta Linn. (Compositae) has been used for the treatment of various parasitic and microbial diseases. OBJECTIVE: To evaluate the antioxidant activity of the ethanol extract of Tagetes erecta roots and its cytotoxicity against prostate and HeLa cancer cell lines followed by activity-guided isolation. MATERIALS AND METHODS: The antioxidant screening was carried out using diphenylpicrylhydrazyl (DPPH) radical scavenging assay with serial concentrations ranging from 2 to 100 ug/mL, and cytotoxicity was evaluated against prostate (PC-3) and HeLa cell lines using microculture tetrazolium test (MTT) assay with concentrations ranging from 500 to 1.89 ug/mL. Isolation of the ethanol extract was carried out using column chromatography whereby 21 isolates were obtained (T1-T21), and the most active isolate was subjected for characterization using ultraviolet (UV), infrared (IR), nuclear magnetic resonance (NMR), and mass spectroscopic techniques. RESULTS: The ethanol extract scavenged DPPH free radicals thereby exhibiting antioxidant activity with an IC50 of 35.9 ug/mL. In addition, the extract conferred noticeable cytotoxicity against the HeLa (LD50 of 164.28 ug/mL) and PC-3 cell lines (LD50 of 407.3 ug/mL). Among all the isolates, T3 showed antioxidant activity with IC50 of 11.56 ug/mL and cytotoxicity with LD50 of 12.5 ug/mL against HeLa and 30.25 ug/mL against PC-3 cell lines and was characterized as 2-ethynyl-5-(thiophen-2-yl) thiophene. DISCUSSION: The new thienyl compound (T3) exhibited profound antioxidant activity and cytotoxicity at relatively lower concentrations than the extract. CONCLUSION: The observations provide support for the ethnobotanical use of the plant. PMID- 22775419 TI - Protective effect of dietary flavonoid quercetin against lipemic-oxidative hepatic injury in hypercholesterolemic rats. AB - CONTEXT: Quercetin, a dietary-derived flavonoid, is ubiquitous in fruits and vegetables and plays important roles in human health by virtue of its antioxidant activity. OBJECTIVE: This study was conducted to investigate the possible modulatory effect of quercetin against hepatic lipemic-oxidative injury in rats fed with a high cholesterol diet (HCD), and to highlight the underlying mechanisms of such effect. MATERIALS AND METHODS: Different groups of male Sprague-Dawley rats were used; one group was treated by gavage with HCD cocktail (1 mL/100 g) whereas another group was orally administered HCD-enriched with quercetin (15 mg/kg). Corresponding control animals were also used. RESULTS: Quercetin administration significantly decreased liver triglycerides (24%), liver total cholesterol (TC) (22%), serum TC (20%), serum low-density lipoprotein cholesterol (31%), and duplicated serum high-density lipoprotein cholesterol (HDL C). This study also revealed that quercetin administration significantly reduced the activity of serum alanine aminotransferase (41%), aspartate aminotransferase (51%), and gamma-glutamyl transpeptidase (G-GT) (35%). Significant inhibition of thiobarbituric acid-reacting substances (40%), together with a valuable enhancement of reduced glutathione (GSH) content (53%) in the liver homogenates, was observed. In addition, quercetin-treated hypercholesterolemic animals exhibited a reasonable improvement of hepatic antioxidant enzymes. Moreover, serum and liver content of nitric oxide (NO) were markedly decreased in this model (26 and 25%, respectively), and were almost normalized following quercetin administration. DISCUSSION AND CONCLUSION: These data revealed that quercetin has the ability to ameliorate HCD-induced lipemic-oxidative injury in rat liver possibly through its antioxidant potential and/or increased NO bioavailability. PMID- 22775421 TI - The evaluation of topical administration of Bellis perennis fraction on circular excision wound healing in Wistar albino rats. AB - CONTEXT: Bellis perennis L. (Asteraceae) has been used traditionally in the treatment of bruises, broken bones, and wounds by European people. OBJECTIVE: To investigate the wound healing activity of B. perennis flowers in Wistar albino rats. MATERIALS AND METHODS: Dried B. perennis flowers were extracted with ethanol, then fractioned with n-butanol and an oinment was prepared. Twelve male adult Wistar rats were used. Six wounds were created for each animal by using circular excision wound model. The first two wounds were treated topically with HOTBp (hydrophilic ointment treatment containing n-butanol fraction). The second two wounds were control group and not treated with anything. The third two wounds were treated only with HOT (hydrophilic ointment treatment without n-butanol fraction). Treatments were applied once a day and lasted for 30 days. Wound samples were excised on days 5(th), 10(th) and 30(th). The percentage of wound healing was calculated by Walker's formula after measurement of the wound area and the tissue samples were examined histopathologically. RESULTS: The percentages of wound closure (HOTBp: 100%; HOT: 85% and control: 87%) and histopathological observations showed that there were statistically significant differences between HOTBp, HOT and control groups (p < 0.05) at 30(th) day. DISCUSSION AND CONCLUSION: Topically administered ointment prepared from the n butanol fraction of B. perennis flowers has a wound healing potential without scar formation in circular excision wound model in rats. Thus, traditional usage of wound healing activity of B. perennis was scientifically verified for the first time. PMID- 22775420 TI - Investigation of the cytocidal potential of Rhinella jimi skin methanol extracts. AB - CONTEXT: Amphibian skins have wide variety of biologically active compounds associated with the natural defenses of these animals. OBJECTIVES: To study the in vitro anticancer activity of methanol extracts of the skin of Rhinella jimi Stevaux (Anura: Bufonidae). MATERIAL AND METHODS: The extract was obtained by cold methanol extraction for 96 h using dried skins (295 mg). The methanol skin extract was dried under reduced pressure, giving a 5.5% yield. In order to test for growth-inhibitory activity, in vitro tests were performed with the following cancer cell lines using concentrations ranging between 0.25-250 ug/mL of the extract by 48 h: K562 (leukemia), MCF-7 (breast), NCI-ADR (breast with MDR phenotype), UACC-62 (melanoma), NCI460 (lung), PCO3 (prostate), HT-29 (colon), OVCAR (ovary), and 786-0 (kidney). RESULTS: The methanol extract of R. jimi produced a growth inhibition in a dose-dependent manner against the most of the assayed cell lines. In addition to the growth inhibition, the extract induced the cell death in the ovary and colon lines (EC50 0.125 and 0.2 ug/mL, respectively), demonstrating 100% of inhibition with 2.5 ug/mL. However, prostate and leukemia cell lines demonstrated less sensitivity, with EC50 of 24 and 235 ug/mL, respectively. This is the first report about the anticancer activity by natural products from the skin of R. jimi. CONCLUSIONS: The methanol extracts of R. jimi significantly affected the growth of several cell lines, demonstrating that these compounds are a potential source of substances that could be utilized in cancer treatments. PMID- 22775422 TI - Sinomenium acutum: a review of chemistry, pharmacology, pharmacokinetics, and clinical use. AB - CONTEXT: Sinomenium acutum (Thumb.) Rehd. et Wils. (Menispermaceae, SA) has been used as a traditional Chinese medicine in the treatment of various diseases for hundreds of years; it possesses favorable effects against autoimmune diseases, especially rheumatoid arthritis (RA). A great number of investigations have been done on SA in the last decade, but they are usually scattered across various publications. OBJECTIVE: The purpose of this article is to summarize and review the published scientific information about the chemical constituents, pharmacological effects, pharmacokinetics, and clinic applications of this plant since 2000. RESULTS: The information for 89 cases included in this review was compiled. The SA contains alkaloids, sterols, phospholipids, and some other components. A great deal of pharmacological and clinic research has been done on sinomenine, a main compound from SA, which mainly focuses on the immune system, cardiovascular system, and nervous system. CONCLUSION: Previous studies strongly support its potential as an effective adaptogenic herbal remedy. There is no doubt that SA is being widely used now and will have extraordinary potential for the future. PMID- 22775423 TI - Biological activities of ethyl acetate extract of different parts of Hyssopus angustifolius. AB - CONTEXT: Hyssopus angustifolius M. Bieb. (Lamiaceae) is one of the most important medicinal plants in Iranian traditional medicine for the treatment of lung inflammation, laryngitis and cough relief. Much attention has been paid to this medicinal plant because of its traditional uses. OBJECTIVE: The present study examined the antioxidant and antihemolytic activities of ethyl acetate extract of stems, leaf and flowers of Hyssopus angustifolius. MATERIALS AND METHODS: Antioxidant activity of extracts was evaluated by employing six different models, i.e., DPPH, nitric oxide and hydrogen peroxide scavenging, metal chelating and reducing power activities and hemoglobin-induced linoleic acid system. Also, antihemolytic activity was evaluated against hydrogen peroxide-induced hemolysis. RESULTS: Flowers extract showed the better activity than leaf and stems extracts in DPPH radical scavenging activity (IC50 was 275.4 +/- 7.6 MUg mL-1). Leaf, stems and flowers extracts showed good nitric oxide scavenging activity (IC50 were 376.6 +/- 11.4 ug mL-1 for flowers, 297.6 +/- 9.6 MUg mL-1 ug mL-1 for leaves and 837.8 +/- 19.2 ug mL-1 for stems). The leaf extract exhibited better hydrogen peroxide scavenging and Fe2+ chelating activity than stems and flowers extracts. In hemoglobin-induced linoleic acid system, all of the extracts exhibited very good activity. Also, extracts show weak reducing power activity. The ethyl acetate extract of leaf showed better antihemolytic activity than the flower and stems (IC50 was 94.0 +/- 2.4 MUg mL-1). DISCUSSION AND CONCLUSION: These findings give a scientific basis to the traditional usage of Hyssopus angustifolius, also showing its potential as rich sources of natural antioxidant compounds. PMID- 22775424 TI - Yoga training improves quality of life in women with asthma. AB - OBJECTIVES: Individuals with asthma frequently suffer with a decrease in quality of life. Yoga has been shown to improve autonomic function in the healthy population and has been used as an alternative therapy to help improve symptoms associated with various diseases. PURPOSE: The purpose of this study was to assess whether 10 weeks of yoga training can improve quality of life and heart rate variability (HRV) in patients with asthma. DESIGN: Nineteen (19) females were randomly assigned to a yoga group or a control group for a 10-week intervention while still following guidelines established by their physician. All subjects answered the St. George's Respiratory Questionnaire (SGRQ) to assess quality of life and performed an isometric handgrip exercise test to assess HRV. RESULTS: Based on the SGRQ, significant improvements (45%, p < 0.05) in quality of life were observed with the yoga training, while no changes were found in the control group. Resting hemodynamic measures improved significantly in the yoga group compared to the control group (p < 0.05). The yoga group decreased parasympathetic modulation (HFnu [normalized units]) pre- to postintervention (0.45 +/- 0.60 to 0.35 +/- 0.06 nu, p<0.05, respectively) in response to the isometric forearm exercise (IFE), whereas the control group did not change. Additionally, the yoga group increased sympathetic (LFnu) (pre 0.47 +/- 0.07 to post 0.60 +/- 0.07 nu, p < 0.05) and sympathovagal modulation (logLF/HF) (pre 4.61 +/- 0.39 to post 5.31 +/- 0.44, p < 0.05, respectively) during IFE with no change in the control group. CONCLUSIONS: Yoga training improved quality of life in women with mild-to-moderate asthma and resulted in decreased parasympathetic and increased sympathetic modulation in response to an IFE. PMID- 22775425 TI - Persistently low transplantation rate of ABO blood type O and highly sensitised patients despite alternative transplantation programs. AB - ABO blood type O and highly sensitised patients have the smallest chance to receive kidney transplantation. Do alternative donation programs increase this chance? In the period studied: 2323 patients were enlisted on the Rotterdam waiting list for a renal transplantation: 435 patients still waiting (WL), 464 delisted without transplantation (DWT). 1424 received deceased donor (DD, 535) or living donor (LD, 889, including 204 alternative) transplantation. Alternative LD programs in our centre are: paired kidney-exchange, altruistic with domino-paired donation and ABO-incompatible donation (ABOi). Compared to populations not transplanted, blood type O recipients are significantly underrepresented in DD and all LD transplantation populations, except the ABOi program. Highly sensitised patients are overrepresented in DD, but underrepresented in all LD transplantation populations. The high transplantation rate of highly sensitised patients was the result of Eurotransplant Acceptable mismatch program (AM). The LD ABOi and DD AM programs are the only alternative donation programs favourable for patients with low chances. While the contribution of direct LD transplantations will increase in time, the relative success rate of low-chance patients will decrease. Beside increasing LD ABOi transplantation, a new DD allocation model favouring both highly immunised and blood type O patients is essential. PMID- 22775426 TI - The complete mitochondrial genome of the giant pill millipede, Sphaerotheriidae sp. (Myriapoda: Diplopoda: Sphaerotheriida). AB - The complete mitochondrial genome (mitogenome) of the millipede Sphaerotheriidae sp. has been studied. The genome is 14,970 bp long and contains the typical complement of 13 protein-coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes. Gene order in Sphaerotheriidae sp. mitogenome is assumed to represent the myriapod ground pattern, which is shared by myriapod-chelicerate clade. PMID- 22775427 TI - The complete mitochondrial genome of the large white-bellied rat, Niviventer excelsior (Rodentia: Muridae). AB - The first complete mitochondrial genome of the large white-bellied rat (Niviventer excelsior) was sequenced and annotated in order to provide a source of phylogenetic characters including an assessment of gene order arrangement. The mitochondrial genome sequence (16,298 bp) of N. excelsior contains 13 protein coding, 2 rRNA and 22 tRNA genes as well as 1 typical control region (D-Loop), which are shared by other mammalian mitochondrial genomes. The codon usage also followed the typical vertebrate pattern except for an unusual CCA stop codon, which was termination codon of Cyt b. The 16 nucleotide insertion was detected in the central conserved domain of d-Loop. The 12 heavy-strand encoded protein coding genes were used to reconstruct the phylogenetic relationships by the Bayesian inference and maximum likelihood methods. Topologies revealed that N. excelsior clustered together with the species in genus Rattus, indicating their closer phylogenetic relationship. PMID- 22775428 TI - The complete mitochondrial genome of scimitar-horned oryx (Oryx dammah). AB - In this study, a blood sample was obtained from a scimitar-horned oryx in Jinan Paomaling World of Wildlife and the complete nucleotide sequence of scimitar horned oryx mitochondrial genome was determined. Sequence analysis showed that the genome structure was in accordance with other bovid species that it contained 22 tRNA genes, 12S rRNA gene, 16S rRNA gene, 13 protein-coding genes and 1 control region. PMID- 22775429 TI - Circulating cell-free mitochondrial DNA as a novel cancer biomarker: opportunities and challenges. AB - The unique characteristics of the mitochondrial genome, such as short length, simple molecular structure, and high copy number, have made monitoring aberrant changes of mitochondrial DNA (mtDNA) quantity an interesting molecular tool for early tumor detection with many advantages over the nuclear genome-based methods. Recently, circulating cell-free (ccf) mtDNA in blood has emerged on the platform as a non-invasive diagnostic and prognostic biomarker for many forms of solid tumors. Accumulating evidence demonstrate that plasma or serum ccf mtDNA levels are significantly different between cancer patients and healthy individuals. Furthermore, quantification of ccf mtDNA levels in circulation may assist in identifying patients from cancer-free healthy population. This minireview attempts to summarize our recent findings in this very promising field of cancer research. The potential technical challenges that we have encountered during the quantitative analysis of ccf mtDNA and mtDNA in general are also briefly discussed. Prospective studies with a larger cohort of patients in various cancer entities are beneficial to precisely define the clinical importance of assessing the ccf mtDNA amount for diagnosing and tracking malignant diseases and their progression. PMID- 22775430 TI - The complete mitogenome sequence of a cave loach Triplophysa rosa (Teleostei, Balitoridae, Nemacheilinae). AB - China is very rich in cavefishes and some detailed studies on their taxonomy and biology have been carried out, but many other aspects such as genetics and evolution need further investigation. Here, we sequenced the complete mitogenome sequence of the Rose Blind Plateau Loach, Triplophysa rosa, and combined with other 27 ostariophysan complete mitogenome sequences, the phylogenetic position of T. rosa was estimated. The 16,585 bp mitogenome of T. rosa was a typical vertebrate mitochondrial genome containing 13 protein-coding, 2 rRNA, 22 tRNA genes, and 1 control region (CR). The CR of T. rosa was characterized by one termination-associated sequence and seven conserved sequence blocks (CSB-B, D, E, F, and CSB I, II, III). Phylogenetic analyses showed that T. rosa belongs to the subfamily Nemacheilinae and formed a sister-group relationship with the genus Barbatula. Further analyses based on the concatenated mitochondrial cyt b and D loop sequences showed that T. rosa clustered with other Triplophysa species, and it was located in the basal position within the genus. In addition, the molecular clock estimations showed that T. rosa might have diverged from other Triplophysa species at about 48.3 million years ago during the rapid uplift period of the Qinghai-Tibetan Plateau. PMID- 22775431 TI - Influence of regression model and incremental test protocol on the relationship between lactate threshold using the maximal-deviation method and performance in female runners. AB - This study examined the influence of the regression model and initial intensity of an incremental test on the relationship between the lactate threshold estimated by the maximal-deviation method and the endurance performance. Sixteen non-competitive, recreational female runners performed a discontinuous incremental treadmill test. The initial speed was set at 7 km . h-1, and increased every 3 min by 1 km . h-1 with a 30-s rest between the stages used for earlobe capillary blood sample collection. Lactate-speed data were fitted by an exponential-plus-constant and a third-order polynomial equation. The lactate threshold was determined for both regression equations, using all the coordinates, excluding the first and excluding the first and second initial points. Mean speed of a 10-km road race was the performance index (3.04 +/- 0.22 m . s-1). The exponentially-derived lactate threshold had a higher correlation (0.98 <= r <= 0.99) and smaller standard error of estimate (SEE) (0.04 <= SEE <= 0.05 m . s-1) with performance than the polynomially-derived equivalent (0.83 <= r <= 0.89; 0.10 <= SEE <= 0.13 m . s-1). The exponential lactate threshold was greater than the polynomial equivalent (P < 0.05). The results suggest that the exponential lactate threshold is a valid performance index that is independent of the initial intensity of the incremental test and better than the polynomial equivalent. PMID- 22775432 TI - Recipient and donor risk factors for surgical complications following kidney transplantation. AB - OBJECTIVE: The aim of this study was to evaluate recipient and donor risk factors that are related to surgical complications after renal transplantation. MATERIAL AND METHODS: In total, 419 kidney transplantations were analysed with regard to the influence of recipient and donor risk factors on the main postoperative surgical complications. RESULTS: The mean follow-up for the entire group was 72.8 months (+/- 54.2 SD). Vascular complications were independently associated with donor age; and urological complications with recipient age >65 years and cyclosporine rather than tacrolimus therapy. Wound complications were independently associated with recipient age, preoperative dialysis time, recipient body mass index (BMI) and cyclosporine rather than tacrolimus therapy. Collections were independently associated with retransplantation, type 2 diabetes mellitus and wound complications. Overall surgical complications were associated with donor age and delayed graft function. In terms of severity, grade I complications were independently associated with recipient age and surgical revision, grade II with recipient age >50 years, grade III with recipient BMI, and grade IV with donor age. CONCLUSIONS: Recipient characteristics are the primary determinants of wound, urological and minor (Clavien grades I, II and III) complications; however, graft or donor characteristics are the primary risk factors for vascular, overall and major (Clavien grade IV) surgical complications. PMID- 22775433 TI - The yield of temporary exclusion of blood donors, exposed to emerging infections abroad. AB - BACKGROUND AND OBJECTIVES: Emerging infections abroad pose a threat to the safety of blood, donated by travelling blood donors. In this study, the yield of donor deferral after travelling was evaluated, by comparing the estimated numbers of infected donors returning from various affected areas. METHODS: A deterministic model was applied to calculate the number of infected donors, returning from six areas affected by outbreaks: Greece - Macedonia (West Nile fever), Italy - Emilia Romagna (West Nile fever), Thailand (chikungunya), Latvia (hepatitis A), central Turkey (Sicilian sandfly fever) and Italy - Tuscany (Toscana sandfly fever). RESULTS: The estimated number of infections among returning blood donors was surprisingly low, ranging from 0.32 West Nile virus-infected donors per year returning from Macedonia (Greece) to approximately 0.005 infected donors per year returning respectively from Tuscany (sandfly fever), Latvia (hepatitis A) and central Turkey (sandfly fever). CONCLUSION: The yield of the temporary exclusion of blood donors travelling to a specific, affected area is low, but the continuous monitoring of emerging infections and the timely assessment of new threats are laborious and imperfect. Safety measures may be instituted after the greatest threat of a new outbreak has passed. A general deferral of travelling donors may be more appropriate than targeted measures. It can be argued that all donors who stayed outside their country or continent of residency should be deferred for 4 weeks. PMID- 22775435 TI - Locked nucleic acid-based in situ hybridisation reveals miR-7a as a hypothalamus enriched microRNA with a distinct expression pattern. AB - MicroRNAs (miRNAs) are short (~22 nucleotides) noncoding RNA molecules that post transcriptionally repress the expression of protein-coding genes by binding to 3' untranslated regions of the target mRNAs. To identify miRNAs selectively expressed within the hypothalamus, a part of the brain that controls vital bodily functions, we employed locked nucleic acid (LNA)-fluorescent in situ hybridisation (FISH). The expression pattern of the mature miRNAs miR-7a, miR-7b, miR-137 and miR-153 in mouse brain tissue sections was investigated. Although all studied miRNAs were present in the hypothalamus, miR-7a, was the only miRNA found to be enriched in the hypothalamus, with low or no expression in other parts of the central nervous system (CNS). Within the hypothalamus, strong miR-7a expression was distinct and restricted to some hypothalamic nuclei and adjacent areas. miR-7a expression was particularly prominent in the subfornical organ, as well as the suprachiasmatic, paraventricular, periventricular, supraoptic, dorsomedial and arcuate nuclei. Identical expression patterns for miR-7a were seen in mouse and rat hypothalamus. By combining LNA-FISH with immunohistochemistry, it was shown that miR-7a was preferentially present in small orexigenic neuropeptide Y/agouti-related protein-containing-neurones located in the ventromedial aspect of the arcuate nucleus but not in large pro opiomelanocortin/cocaine- and amphetamine-regulated transcript-containing anorexigenic neurones of the ventrolateral part of the arcuate nucleus. The limited and distinct expression of miR-7a in the CNS suggests that miR-7a has a role in post-transcriptional regulation in hypothalamic neurones. Particularly strong expression of miR-7a in neurones located in the ventromedial division of the arcuate nucleus, a subregion with a weak blood-brain barrier, raises the possibility that miR-7a is influenced by circulating hormones and is a regulator of the genes involved in body weight control. PMID- 22775436 TI - Synthesis and investigation of [B20H17O(CH2)5]3-, a novel solvent complex of the [B20H18]4- ion. AB - Reaction of the [trans-B(20)H(18)](2-) ion with the n-butoxide ion, formed in situ from reaction of n-butanol and NaH, in tetrahydropyran (THP) produces in good yield an unexpected and isolable solvent-coordinated polyhedral borane anion, [ae-B(20)H(17)O(CH(2))(5)](3-). The anticipated product of nucleophilic attack, [ae-B(20)H(17)On-Bu](4-), is not observed under the reaction conditions. The solvent-coordinated product is also formed in the presence of either ethoxide or carbamate ion but is not observed if the ethoxide or carbamate ion is not present in stoichiometric amounts. In the presence of the n-butanethiol anion, the coordinated THP ring undergoes a ring-opening reaction, yielding the [ae B(20)H(17)O(CH(2))(5)Sn-Bu](4-) anion. Ring opening is also observed in the presence of the ethoxide ion in refluxing THP. Isolation of the previously proposed analogous solvent-coordinated tetrahydrofuran (THF) product, [ae B(20)H(17)O(CH(2))(4)](3-), was unsuccessful; however, the product resulting from ring opening of THF by the n-butanethiol anion is reported. PMID- 22775434 TI - The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. AB - Cocoa powder and chocolate contain numerous substances among which there is a quite large percentage of antioxidant molecules, mainly flavonoids, most abundantly found in the form of epicatechin. These substances display several beneficial actions on the brain. They enter the brain and induce widespread stimulation of brain perfusion. They also provoke angiogenesis, neurogenesis and changes in neuron morphology, mainly in regions involved in learning and memory. Epicatechin improves various aspects of cognition in animals and humans. Chocolate also induces positive effects on mood and is often consumed under emotional stress. In addition, flavonoids preserve cognitive abilities during ageing in rats, lower the risk for developing Alzheimer's disease and decrease the risk of stroke in humans. In addition to their beneficial effects on the vascular system and on cerebral blood flow, flavonoids interact with signalization cascades involving protein and lipid kinases that lead to the inhibition of neuronal death by apoptosis induced by neurotoxicants such as oxygen radicals, and promote neuronal survival and synaptic plasticity. The present review intends to review the data available on the effects of cocoa and chocolate on brain health and cognitive abilities. PMID- 22775437 TI - Large deletions and splicing-site mutations in the STK11 gene in Peutz-Jeghers Chilean families. AB - Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by mucocutaneous melanocytic macules, gastrointestinal hamartomatous polyposis and an increased risk of various neoplasms. Germline mutations in the serine/threonine kinase 11 (STK11) gene have been identified as a cause for PJS. The aim of this study was to characterize the genotype of Chilean PJS patients. Mutation screening of 13 patients from eight PJS families was performed using a single strand conformation polymorphism analysis, DNA sequencing and multiplex ligation-dependent probe amplification assay. The breakpoints of the genomic rearrangements were assessed by a long-range polymerase chain reaction and sequencing. The results revealed the existence of seven different pathogenic mutations in STK11 gene in seven unrelated families, including three point mutations and four large genomic deletions. Three of these point mutations (43%, 3/7) may be considered as novel. Our results showed that a germline mutation is present in STK11 in 88% of probands fulfilling the diagnostic criteria of PJS. In this study, the combination of two different experimental approaches in the screening of the STK11 in PJS, led to a higher percentage of mutation detection. PMID- 22775438 TI - Role of Met80 and Tyr67 in the low-pH conformational equilibria of cytochrome c. AB - The low-pH conformational equilibria of ferric yeast iso-1 cytochrome c (ycc) and its M80A, M80A/Y67H, and M80A/Y67A variants were studied from pH 7 to 2 at low ionic strength through electronic absorption, magnetic circular dichroism, and resonance Raman spectroscopies. For wild-type ycc, the protein structure, axial heme ligands, and spin state of the iron atom convert from the native folded His/Met low-spin (LS) form to a molten globule His/H(2)O high-spin (HS) form and a totally unfolded bis-aquo HS state, in a single cooperative transition with an apparent pK(a) of ~3.0. An analogous cooperative transition occurs for the M80A and M80A/Y67H variants. This is preceded by protonation of heme propionate-7, with a pK(a) of ~4.2, and by an equilibrium between a His/OH(-)-ligated LS and a His/H(2)O-ligated HS conformer, with a pK(a) of ~5.9. In the M80A/Y67A variant, the cooperative low-pH transition is split into two distinct processes because of an increased stability of the molten globule state that is formed at higher pH values than the other species. These data show that removal of the axial methionine ligand does not significantly alter the mechanism of acidic unfolding and the ranges of stability of low-pH conformers. Instead, removal of a hydrogen bonding partner at position 67 increases the stability of the molten globule and renders cytochrome c more susceptible to acid unfolding. This underlines the key role played by Tyr67 in stabilizing the three-dimensional structure of cytochrome c by means of the hydrogen bonding network connecting the Omega loops formed by residues 71-85 and 40-57. PMID- 22775439 TI - BRAF mutation analysis of only one metastatic lesion can restrict the treatment of melanoma: a case report. PMID- 22775440 TI - High throughput synthesis of extended pyrazolo[3,4-d]dihydropyrimidines. AB - Thirteen 5-hetarylaminopyrazoles were synthesized in 62-93% yield through the arylation of 1-isopropyl- and 1-phenyl-5-aminopyrazoles with electrophilic hetarylhalides under optimized conditions. Condensation of 5 hetarylaminopyrazoles with carbonyl compounds facilitated by AcOH or Me(3)SiCl furnished 23 pyrazolo[3,4-d]dihydropyrimidines in 69-86% yield. The target compounds were isolated through simple crystallization. The scope and limitation of the method are discussed. PMID- 22775441 TI - 3-Hydroxy-3-methylglutaryl flavonol glycosides from Oxytropis falcata. AB - Five new 3-hydroxy-3-methylglutaryl (HMG) flavonol 3-O-glycosides, named oxytroflavosides A-E (1-5), and two new rhamnocitrin 3-O-glycosides, oxytroflavosides F and G (6 and 7) were isolated from the n-BuOH-soluble fraction of an EtOH extract of Oxytropis falcata together with seven known kaempferol glycosides (8-14), of which six were isolated from the genus Oxytropis for the first time. The structures of these compounds were elucidated by spectroscopic techniques and chemical methods. The absolute configuration of HMG in compounds 1 5 was determined to be S through spectroscopic analysis of the mevalonamide obtained by amidation and reduction of the HMG moiety. Compounds 1-10 were evaluated for anti-inflammatory activities using lipopolysaccharide-induced RAW 264.7 cells, but none of them showed inhibitory effects on NO production. PMID- 22775442 TI - Regulation of the Arabidopsis anther transcriptome by DYT1 for pollen development. AB - Several genes encoding transcription factors have been shown to be essential for male fertility in plants, suggesting that transcriptional regulation is a major mechanism controlling anther development in Arabidopsis. DYSFUNCTIONAL TAPETUM 1 (DYT1), a putative bHLH transcription factor, plays a critical role in regulating tapetum function and pollen development. Here, we compare the transcriptomes of young anthers of wild-type and the dyt1 mutant, demonstrating that DYT1 is upstream of at least 22 genes encoding transcription factors and regulates the expression of a large number of genes, including genes involved in specific metabolic pathways. We also show that DYT1 can bind to DNA in a sequence-specific manner in vitro, and induction of DYT1 activity in vivo activated the expression of the downstream transcription factor genes MYB35 and MS1. We generated DYT1 SRDX transgenic plants whose fertility was dramatically reduced, implying that DYT1 probably acts as a transcriptional activator. Furthermore, we used yeast two hybrid assays to show that DYT1 forms homodimers and heterodimers with other bHLH transcription factors. Our results demonstrate the important role of DYT1 in regulating anther transcriptome and function, and supporting normal pollen development. PMID- 22775443 TI - Nicotine behavioral sensitization in Lewis and Fischer male rats. AB - Individuals with greater nicotine-reactivity may be more likely to initiate and maintain cigarette-smoking behavior than individuals with less nicotine reactivity. In rats, behavioral sensitization reflects a progressive increase in the psychomotor response to drugs of abuse thought to result from neuroplasticity in brain regions that mediate their motivational effects. Studying nicotine behavioral sensitization in rats with differential nicotine preference and intake, such as Lewis and Fischer rats, may provide clues about the role of nicotine-reactivity in tobacco use. Rat strain differences in nicotine behavioral sensitization may contribute to strain differences in nicotine preference, sensitivity, and intake. In the present research, nicotine behavioral sensitization to multiple doses was examined in Lewis and Fischer rats. Subjects were 96 late adolescent male (48 Fischer, 48 Lewis) rats. Rats received subcutaneous injections of nicotine (0.2, 0.4, 0.7, 1.4, 2.8 mg/kg) or saline daily, and locomotor activity was measured immediately following injections on alternating days to examine sensitization. Behavioral sensitization occurred in both rat strains at the 0.2, 0.4, 0.7, and 1.4 mg/kg nicotine doses, but did not differ between Lewis and Fischer rats. The pattern of horizontal activity that occurred in response to the 2.8 mg/kg nicotine dose did not reflect behavioral sensitization. Results indicate that nicotine behavioral sensitization occurred in Lewis and Fischer rats, and did not differ between the two rat strains. It can be concluded that reported rat strain differences in nicotine intake, sensitivity, and preference do not result from rat strain differences in nicotine behavioral sensitization. PMID- 22775444 TI - Influence of ethanol on swelling and release behaviors of Carbopol((r))-based tablets. AB - The aim of this work was to investigate the effect of ethanol on the in vitro swelling and release behaviors of Carbopol((r))-based tablets. The swelling behavior of drug-free compacts and the release of model drugs (metformin HCl, caffeine and theophylline) from matrix tablets were evaluated in acidic and buffered media with 0, 20 and 40% (v/v) ethanol. Release data were analyzed by fitting to Higuchi and Peppas models and calculation of similarity factor (f2). ANOVA tests were performed to determine significant factors on swelling and release. It was found that ethanol affects swelling and erosion of drug-free Carbopol((r)) compacts, and the effect was highly dependent on medium pH. For matrix tablets, no dose dumping due to ethanol was manifested. The release rate and mechanism, however, were significantly affected by ethanol concentration as indicated by ANOVA applied to the constant, KH, from Higuchi model and the exponent, n, from Peppas model, respectively. The effect of ethanol on release was further confirmed by similarity factor results, which indicated that ethanol led to different release profiles (f2 < 50) in seven of eight cases for matrices containing metformin HCl and in three of eight cases for matrices containing caffeine and theophylline. PMID- 22775445 TI - Limitations on diversity in basic science departments. AB - It has been over 30 years since the beginning of efforts to improve diversity in academia. We can identify four major stages: (1) early and continuing efforts to diversify the pipeline by increasing numbers of women and minorities getting advanced degrees, particularly in science, technology, engineering, and math (STEM); (2) requiring academic institutions to develop their own "affirmative action plans" for hiring and promotion; (3) introducing mentoring programs and coping strategies to help women and minorities deal with faculty practices from an earlier era; (4) asking academic institutions to rethink their practices and policies with an eye toward enabling more faculty diversity, a process known as institutional transformation. The thesis of this article is that research intensive basic science departments of highly ranked U.S. medical schools are stuck at stage 3, resulting in a less diverse tenured and tenure-track faculty than seen in well-funded science departments of major universities. A review of Web-based records of research-intensive departments in universities with both medical school and nonmedical school departments indicates that the proportion of women and Black faculty in science departments of medical schools is lower than the proportion in similarly research-intensive university science departments. Expectations for faculty productivity in research-intensive medical school departments versus university-based departments may lead to these differences in faculty diversity. PMID- 22775446 TI - Patterns and predictors of use of warfarin and other common long-term medications in patients with atrial fibrillation. AB - BACKGROUND AND OBJECTIVE: No study has been published that compared persistence and discontinuation of warfarin with other long-term medications in patients with atrial fibrillation (AF). The objective of this study was to evaluate persistence and discontinuation patterns in AF patients taking warfarin and other common long term medications and identify predictors of persistence and discontinuation in this population. METHODS: Patients with warfarin prescription within 3 months after AF hospitalization discharge and 12-month data before and after the first prescription were evaluated using administrative claims data (1 January 2005 - 31 December 2007). For comparison, persistence patterns for other long-term medications for treatment of hypertension, hyperglycemia, heart disease, and dyslipidemia, including once- (od) and twice- (bid) daily medications, were evaluated. Non-persistence was defined as the presence of a >=60-day gap in medication use. Permanent discontinuation was defined as no use of the medication for >=90 days until the end of the follow-up period. Multivariate analysis was conducted to identify predictors of warfarin non-persistence and discontinuation. RESULTS: 28 384 patients with AF were identified; 16 036 (56.5%) had a warfarin prescription following AF hospitalization. 53.5% of warfarin users were persistent for at least 1 year, similar to other long-term medications commonly prescribed to the AF population (ranging between 45.2% and 61.3%). 42.6% of warfarin users permanently discontinued warfarin within 1 year, also consistent with the discontinuation rate of 32.9-52.0% of other long-term medications. Residence in the South and West regions of the US, history of cardiac dysrhythmias, and warfarin cost-sharing significantly decreased the likelihood of warfarin persistence and increased the likelihood of discontinuation, while older age, history of ischemic stroke, and warfarin use before hospitalization significantly increased warfarin persistence and decreased the likelihood of discontinuation. Adherence of od and bid medications was similar. CONCLUSION: Persistence and discontinuation with warfarin in patients with AF is consistent with other long-term medications. Identifying factors associated with non persistence and discontinuation with long-term medications can help in developing targeted adherence programs. PMID- 22775447 TI - The persistence of the association between adolescent cannabis use and common mental disorders into young adulthood. AB - AIMS: Debate continues about whether the association between cannabis use in adolescence and common mental disorders is causal. Most reports have focused on associations in adolescence, with few studies extending into adulthood. We examine the association from adolescence until the age of 29 years in a representative prospective cohort of young Australians. DESIGN: Nine-wave, 15 year representative longitudinal cohort study, with six waves of data collection in adolescence (mean age 14.9-17.4 years) and three in young adulthood (mean age 20.7, 24.1 and 29.1 years). PARTICIPANTS: Participants were a cohort of 1943 recruited in secondary school and surveyed at each wave when possible from mid teen age to their late 20s. SETTING: Victoria, Australia. MEASUREMENTS: Psychiatric morbidity was assessed with the Revised Clinical Interview Schedule (CIS-R) at each adolescent wave, and as Composite International Diagnostic Interview (CIDI)-defined ICD-10 major depressive episode and anxiety disorder at 29 years. Frequency of cannabis use was measured in the past 6 months in adolescence. Cannabis use frequency in the last year and DSM-IV cannabis dependence were assessed at 29 years. Cross-sectional and prospective associations of these outcomes with cannabis use and dependence were estimated as odds ratios (OR), using multivariable logistic regression models, with the outcomes of interest, major depressive episode (MDE) and anxiety disorder (AD) at 29 years. FINDINGS: There were no consistent associations between adolescent cannabis use and depression at age 29 years. Daily cannabis use was associated with anxiety disorder at 29 years [adjusted OR 2.5, 95% confidence interval (CI):< 1.2-5.2], as was cannabis dependence (adjusted OR 2.2, 95% CI: 1.1-4.4). Among weekly+ adolescent cannabis users, those who continued to use cannabis use daily at 29 years remained at significantly increased odds of anxiety disorder (adjusted OR 3.2, 95% CI: 1.1-9.2). CONCLUSIONS: Regular (particularly daily) adolescent cannabis use is associated consistently with anxiety, but not depressive disorder, in adolescence and late young adulthood, even among regular users who then cease using the drug. It is possible that early cannabis exposure causes enduring mental health risks in the general cannabis-using adolescent population. PMID- 22775449 TI - Endothelial function measured using flow-mediated dilation in polycystic ovary syndrome: a meta-analysis of the observational studies. AB - OBJECTIVE: Women with polycystic ovary syndrome (PCOS) demonstrate an increased prevalence of cardiovascular disease (CVD) risk factors. Previous researchers have compared flow-mediated dilation (FMD), an early marker of CVD, in women with and without PCOS. Evidence for a PCOS-mediated reduction in FMD remains equivocal, potentially because of study differences in cohort-matching and measurement approaches. The aims of this systematic review and meta-analysis were to examine to what extent FMD is impaired in PCOS and to explore the influence of potential moderators of FMD reduction, such as age and BMI. DESIGN: A systematic review and meta-analysis of published observational studies comparing FMD in PCOS with control women. PATIENTS: Twenty-one published studies were included (PCOS, n = 908; controls, n = 566). A subanalysis, using tighter inclusion criteria, involved seven studies (PCOS, n = 402; control, n = 251). MEASUREMENTS: Mean differences in FMD between PCOS and controls were synthesized. The subanalysis was delimited to the inclusion of age and BMI-matched controls. These factors were then explored as moderators using meta-regression. RESULTS: The pooled mean FMD was 3.4% (95% CI=1.9, 4.9) lower in PCOS compared with control women, with substantial heterogeneity between studies. In the subanalysis, the PCOS-mediated reduction in FMD was 4.1% (95% CI=2.7, 5.5). Heterogeneity remained substantial (I(2) =81%). Subsequent meta-regression indicated that the magnitude of FMD difference was not influenced by BMI (P = 0.17) nor age (P = 0.38). CONCLUSIONS: This systematic research synthesis indicates that endothelial function is compromised in PCOS women, even if they are young and nonobese. PMID- 22775450 TI - Photoluminescence and trans -> cis photoisomerization of aminostyrene-conjugated phenylpyridine C^N ligands and their complexes with platinum(II): the styryl position and the amino substituent effects. AB - The synthesis, electronic spectra, photochemical properties, and DFT calculations of four phenylpyridine (ppy)-derived C^N ligands and their cyclometalated [(C^N)Pt(II)(acac)] (C^N = trans-n-(4-NR2-styryl)-2-phenylpyridine, where n = 3' or 4 and R = Me or Ph, and acac = acetylacetonate) complexes are reported. The results allow one to address the effects of the styryl position (n = 3' or 4) and the amino N-substituents (N-Me or N-Ph) on the photoluminescence and trans -> cis photoisomerization quantum efficiencies (Phif and Phitc) of the free ligands and the Pt complexes. In general, the styryl position effect is more significant than the amino substituent effect. The relative Phif and Phitc values are distinct between the free ligands and the corresponding Pt complexes. However, the phenomenon of Phif + 2Phitc ~ 1.0 is observed for all cases in solutions at room temperature. This phenomenon is interpreted by the conventional one-bond-twist mechanism for photoisomerization, which is an activated process in S1 but barrierless in T1. We conclude that ca. 50% of the C?C bond torsion in the excited-state manifold leads to the cis isomer and the excited-state deactivations are dominated by fluorescence and trans -> cis isomerization for both the ligands and the complexes. PMID- 22775448 TI - A preliminary study of the effects of repeated massage on hypothalamic-pituitary adrenal and immune function in healthy individuals: a study of mechanisms of action and dosage. AB - OBJECTIVES: This study gathers preliminary data about the biologic effects of repeated Swedish massage therapy compared to a light-touch control condition. DESIGN: The study design was a 5-week comparison of repeated Swedish massage and light touch on oxytocin (OT), arginine-vasopressin (AVP), adrenal corticotropin hormone (ACTH), cortisol (CORT), circulating phenotypic lymphocyte markers, and mitogen-stimulated cytokine function. SETTING: The setting was an outpatient research unit in an academic medical center. PARTICIPANTS: The study subjects were medically and psychiatrically healthy young adults. INTERVENTION: The study comprised 45 minutes of Swedish massage or light touch, using highly specified and identical protocols, either weekly or twice weekly for 5 weeks. OUTCOME MEASURES: The outcome measures were mean differences between massage and light touch on OT, AVP, ACTH, CORT, lymphocyte markers, and cytokine levels. RESULTS: Compared to the touch control condition, weekly Swedish massage stimulated a sustained pattern of increased circulating phenotypic lymphocyte markers and decreased mitogen-stimulated cytokine production, similar to what was previously reported for a single massage session, while having minimal effect on hypothalamic-pituitary-adrenal function. Twice-weekly massage produced a different response pattern with increased OT levels, decreased AVP, and decreased CORT but little effect on circulating lymphocyte phenotypic markers and a slight increase in mitogen-stimulated interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-1b and IL-2 levels, suggesting increased production of pro inflammatory cytokines. CONCLUSIONS: There are sustained cumulative biologic actions for the massage and touch interventions that persist for several days or a week, and these differ profoundly depending on the dosage (frequency) of sessions. Confirmatory studies in larger samples are needed. PMID- 22775451 TI - A protein disulfide isomerase/thioredoxin-1 complex is physically attached to exofacial membrane tumor necrosis factor receptors: overexpression in chronic lymphocytic leukemia cells. AB - AIMS: The 3D structures and functions of cysteine-rich receptors such as tumor necrosis factor receptors (TNFRs) are redox-modulated by dithiol-disulfide exchange. TNFR superfamily members participate in growth regulation in B-cell chronic lymphocytic leukemia (CLL), and tissue stromal cells interact with leukemia cells, profoundly affecting their viability via release of redox-active components, including cysteine, thioredoxin-1 (Trx1), and Trx reductase. Trx1 was previously shown to enhance release of TNF, which acts as an autocrine/paracrine growth factor in CLL. The nature of the mechanism is not known, however. Here, we investigated whether Trx1 and protein disulfide isomerase (PDI), a chaperone and Trx-family member, may interact with TNFRs. RESULTS: We found direct physical association between PDI and TNFR1 or TNFR2 by coclustering and affinity isolation. PDI (57 kDa) formed covalent/reduction-sensitive 69-kDa complexes with Trx1 (12 kDa) in a majority of CLL cell samples, detected at low levels only in control B-cells. Functionally, the TNF/TNFR signaling via the nuclear factor kappa B-driven autocrine loop was disrupted in a dose-dependent fashion by PDI inhibitors bacitracin, anti-PDI, or anti-Trx1 antibodies, resulting in reduced viability. PDI was significantly overexpressed in immunoglobulin heavy-chain variable (IGHV) unmutated versus mutated CLL (p=0.0102), and amplified TNF release was observed in the former group. INNOVATION: This study points out a previously unrecognized physical and functional association of TNFRs with the redox-active proteins PDI and Trx1. CONCLUSION: We describe here a new level of TNF regulation, in which membrane TNFRs are redox controlled at the exofacial surface by PDI/Trx1. These findings shed new light on the observed survival benefit in CLL B-cells exerted by TNFR-superfamily ligands and point at potential therapeutic strategies. PMID- 22775452 TI - A fluorescence light-up Ag nanocluster probe that discriminates single-nucleotide variants by emission color. AB - Rapid and precise screening of small genetic variations, such as single nucleotide polymorphisms (SNPs), among an individual's genome is still an unmet challenge at point-of-care settings. One crucial step toward this goal is the development of discrimination probes that require no enzymatic reaction and are easy to use. Here we report a new type of fluorescent molecular probe, termed a chameleon NanoCluster Beacon (cNCB), that lights up into different colors upon binding SNP targets. NanoCluster Beacons (NCBs) are collections of a small number of Ag atoms templated on single-stranded DNA that fluoresce strongly when placed in proximity to particular DNA sequences, termed enhancers. Here we show the fluorescence emission color of a NCB can change substantially (a shift of 60-70 nm in the emission maximum) depending upon the alignment between the silver nanocluster and the DNA enhancer sequence. Chameleon NCBs exploit this color shift to directly detect SNPs, based on the fact that different SNPs produce a different alignment between the Ag nanocluster and the enhancer. This SNP detection method has been validated on all single-nucleotide substitution scenarios in three synthetic DNA targets, in six disease-related SNP targets, and in two clinical samples taken from patients with ovarian serous borderline tumors. Samples with single-nucleotide variations can be easily identified by the naked eye under UV excitation, making this method a reliable and low-cost assay with a simple readout format. PMID- 22775453 TI - Copy neutral LOH of FANC F gene: implication on differential diagnosis and treatment of aplastic anemia: letter. PMID- 22775454 TI - A molecular simulation based assessment of binding of metal ions on micelles. AB - An assessment of the ability of a micellar surface to bind different metal ions using molecular simulation is presented in this study. Sodium dodecyl sulfate (SDS) is considered as the anionic surfactant. Various relevant characteristics of SDS-metal ion systems are estimated to quantify preferential binding of metal ions. These are electrostatic energy, total potential energy of the system, radial distribution function, and entropy and free energy change of the system. By examining these parameters, the relative extents of binding of different metal ions to the micellar surface are assessed. PMID- 22775455 TI - Lactate dehydrogenase in hypothermia-treated newborn infants with hypoxic ischaemic encephalopathy. AB - AIMS: We investigated whether plasma lactate dehydrogenase (LDH) predicts outcome in hypothermia (HT)-treated term infants with moderate/severe hypoxic ischaemic encephalopathy (HIE) and additionally whether LDH differs between infants with evidence for acute and nonacute perinatal insults and postnatal collapse (PNC). METHODS: Data from HT-treated infants with HIE (n = 39) were analysed retrospectively. Adverse outcome was defined as a Mental and/or Psychomotor Developmental Index (Bayley Scales of Infant Development II), at 18 months <70. The likely timing of insult onset was assessed in infants with an LDH sample obtained within 6 h of birth or PNC (n = 20). RESULTS: LDH differed between the favourable/adverse outcome groups at the end of HT treatment (median (IQR) 1540 (1400-1950)U/L vs. 3555 (3003-8705)U/L, (p < 0.01)). All infants (n = 22) with LDH <2085U/L had a favourable outcome while 6 of 11 infants with LDH >= 2085U/L had an adverse outcome. LDH in those who died (n = 4) was higher than the favourable outcome group (5090 (2915-12222)U/L, (p < 0.01)) but sampled earlier. Early LDH differed significantly (p < 0.01) between infants with evidence for acute or nonacute insults or PNC. CONCLUSION: THESE results offer a biomarker, with high negative predictive value in the assessment of outcome in HT-treated term infants, needing prospective validation. PMID- 22775456 TI - Methylenetetrahydrofolate reductase polymorphisms C677T and risk of autism in the Chinese Han population. AB - Causes of autism are still unknown. Some studies have shown that autism might be associated with metabolic abnormalities in the folate/homocysteine pathway, which is involved in DNA methylation, thus altering gene expression. The association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms and the risk of autism is still controversial and ambiguous. The purpose of this study was to examine the effect of the MTHFR C677T polymorphism on the autism risk in the Chinese Han population. A population-based case-control study was conducted in 186 children with autism and 186 controls. The MTHFR C677T polymorphisms were determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of genotype MTHFR 677TT in children with autism (16.1%) was significantly higher (odds ratio [OR]=2.04; 95% confidence interval [CI]=1.07, 3.89; p=0.03] than those in controls (8.6%). When stratifying by select-item scores on the Autism Diagnostic Interview-Revised, it was found that children with current overactivity had a significantly higher frequency of the MTHFR 677TT genotype (OR=2.77, 95% CI=1.17, 6.60; p=0.02) than those without. This study suggested that MTHFR C677T is a risk factor of autism in Chinese Han children. PMID- 22775457 TI - Proliferative capacity and pluripotent characteristics of porcine adult stem cells derived from adipose tissue and bone marrow. AB - Direct reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) provides an invaluable resource for regenerative medicine. Because of some ethical and logistical barriers, human iPSCs cannot be used to generate a chimera, which is one of markers representing pluripotency. As the most attractive model for preclinical studies, pigs offer another path to improve clinical medicine. In this study, porcine adult stem cells (pASCs), including adipose mesenchymal stem cells (AMSCs) and bone marrow mesenchymal stem cells (BMSCs), were collected and cultured under the same conditions in vitro. Real time PCR, immunocytochemical staining, apoptosis analysis, and induced differentiation and reprogramming techniques were used to investigate the proliferative capacity and pluripotent characteristics of pASCs. Our results showed that both AMSCs and BMSCs displayed a similar immunophenotype, and their proliferative capacity appeared as a downward trend as the cell passage number increased. The cell proliferative capacity of AMSCs was significantly lower than that of BMSCs (p<0.05). Moreover, each type of pASCs went through 20 passages without undergoing alterations in the expression of reprogramming transcriptional factors (Oct4, Sox2, c-Myc, and Nanog). All pASCs had adipogenic and osteogenic differentiation potential. In addition, they also could be reprogrammed to pig induced pluripotent stem cells (piPSCs) with similar time and efficiency. In conclusion, porcine BMSCs had a higher proliferative capacity than AMSCs, and the pluripotency of pASCs was stable in long-term culture. PMID- 22775458 TI - Conformational selection or induced fit? A critical appraisal of the kinetic mechanism. AB - For almost five decades, two competing mechanisms of ligand recognition, conformational selection and induced fit, have dominated our interpretation of ligand binding in biological macromolecules. When binding-dissociation events are fast compared to conformational transitions, the rate of approach to equilibrium, k(obs), becomes diagnostic of conformational selection or induced fit based on whether it decreases or increases, respectively, with the ligand concentration, [L]. However, this simple conclusion based on the rapid equilibrium approximation is not valid in general. Here we show that conformational selection is associated with a rich repertoire of kinetic properties, with k(obs) decreasing or increasing with [L] depending on the relative magnitude of the rate of ligand dissociation, k(off), and the rate of conformational isomerization, k(r). We prove that, even for the simplest two-step mechanism of ligand binding, a decrease in k(obs) with [L] is unequivocal evidence of conformational selection, but an increase in k(obs) with [L] is not unequivocal evidence of induced fit. Ligand binding to glucokinase, thrombin, and its precursor prethrombin-2 are used as relevant examples. We conclude that conformational selection as a mechanism for a ligand binding to its target may be far more common than currently believed. PMID- 22775459 TI - Impact of gynecological screening in Lynch syndrome carriers with an MSH2 mutation. AB - Lifetime risk of developing endometrial cancer in Lynch syndrome carriers is very high and females are also at an increased risk of developing ovarian cancer. The aim of the study was to determine the impact of gynecological screening in MSH2 mutation carriers. Gynecological cancer incidence and overall survival was compared in female mutation carriers who received gynecological screening (cases) and in matched controls. Controls were randomly selected from non-screened mutation carriers who were alive and disease-free at the age the case entered the screening program. Median age to diagnosis of gynecological cancer was 54 years in the screened group compared to 56 years in controls (p = 0.50). Stage I or II cancer was diagnosed in 92% of screened patients compared to 71% in the control group (p = 0.17). Two of three deaths in the screened group were the result of ovarian cancer. Mean survival in the screened group was 79 years compared to 69 years in the control group (p = 0.11), likely associated with concomitant colonoscopy screening. Gynecological screening did not result in earlier gynecologic cancer detection and despite screening two young women died from ovarian cancer suggesting that prophylactic hysterectomy with bilateral salpingo oophorectomy be considered in female mutation carriers who have completed childbearing. PMID- 22775460 TI - Syntheses and luminescent properties of 3,5-diphenylpyrazolato-bridged heteropolynuclear platinum complexes. The influence of chloride ligands on the emission energy revealed by the systematic replacement of chloride ligands by 3,5 dimethylpyrazolate. AB - Heteropolynuclear Pt(II) complexes with 3,5-diphenylpyrazolate [Pt(2)Ag(4)(MU Cl)(2)(MU-Ph(2)pz)(6)] (3), [Pt(2)Ag(2)Cl(2)(MU-Ph(2)pz)(4)(Ph(2)pzH)(2)] (4), [Pt(2)Cu(2)Cl(2)(MU-Ph(2)pz)(4)(Ph(2)pzH)(2)] (5), [Pt(2)Ag(4)(MU-Cl)(MU Me(2)pz)(MU-Ph(2)pz)(6)] (7), and [Pt(2)Ag(4)(MU-Me(2)pz)(2)(MU-Ph(2)pz)(6)] (8) have been prepared and structurally characterized. These complexes are luminescent except for 5 in the solid state at an ambient temperature with emissions of red-orange (3), orange (4), yellow-orange (7), and green (8) light, respectively. Systematic red shift of the emission energies with the number of chloride ligands was observed for 3, 7, and 8. DFT calculations indicate that the highest occupied molecular orbital (HOMO) as well as HOMO-1 of the heterohexanuclear complexes, 3, 7, and 8, having Pt(2)Ag(4) core, mainly consist of ddelta orbital of Pt(II) and pi orbitals of Ph(2)pz ligands, while the lowest unoccupied molecular orbital (LUMO) of these complexes mainly consists of in phase combination of 6p of two Pt(II) centers and 5p of four Ag(I) centers. It is likely that the emissions of 3, 7, and 8 are attributed to emissive states derived from the Pt(2)(d)/pi -> Pt(2)Ag(4) transitions, the emission energy of which depends on the ratio of chloride ligands to pyrazolate ligands. PMID- 22775461 TI - The effect of glucose concentrations in the medium on expression of insulin receptors in human lymphocytes B and T: an in vitro study. AB - CONTEXT: Insulin is one of the most-known factors that influence the intensity of cell-bound glucose transport. However, in order to react to this hormone, a cell needs specific receptors present in its membrane. The aim of this work was to investigate the insulin receptor expression in B and T cells under incubation with pathological glucose concentrations, respond hyperglycemia and hypoglycemia. MATERIALS AND METHODS: Isolated B and T cells were cultivated in different concentrations of glucose (high, low and normal). The expression of insulin receptors was investigated using methods of immunocytochemistry and flow cytometry. RESULTS: Incubation for 24 h of lymphocytes in pathological glucose concentrations seems to only have a slight influence on the expression of insulin receptors. No insulin receptor expression has been found in lymphocytes T incubated in both pathological concentrations of glucose. Different concentrations of glucose in the incubation medium were found to only marginally influence expression of insulin receptors in lymphocytes B. CONCLUSIONS: Pathological concentrations of glucose in medium cause a decrease in the percent of cells which show expression of insulin receptors in comparison with normal glucose concentration. Thus, it appears highly probable that the insulin receptors did not arise under pathological glucose concentration in these cells de novo, but in little percent lymphocytes have existed there earlier, before the incubation. PMID- 22775462 TI - Platelet-associated antibodies, cellular immunity and FCGR3a genotype influence the response to rituximab in immune thrombocytopenia. AB - Rituximab is widely used in autoimmune diseases including immune thrombocytopenia (ITP), although the mechanism of effect remains unclear. This study describes the effects of rituximab on platelet-associated antibodies (PA-APAs), B and T cell counts and clonality ( IGHV and TRG@ gene rearrangements), FCGR3A (FcgammaRIIIa) and FCGR2A (FcgammaRIIa) polymorphisms and correlation to anti-CD40 ligand (CD40L) response. PA-APA levels fell more frequently in responders (6/8) than in non-responders (2/10: P = 0.08-0.15). Two responders had no PA-APAs. Two non responders with a fall in PA-APAs had very high CD8 levels. One non-responder had a B cell clone, one responder and one non-responder had a T cell clone. 15/16 patients had the same responses to rituximab and antiCD40L. Patients with FCGR3A V/V polymorphisms were more likely to respond to rituximab (P = 0.03). In summary, the fall in PA-APAs in responders confirms the humoural effect of rituximab. Failure to respond in patients with very high CD8 levels, despite PA APA fall indicates a role for T cell-mediated platelet/megakaryocyte destruction. Concordance of response to anti-CD40L suggests autoantibody-producing cells are under T cell control. Finally, the effect of FCGR polymorphisms on response confirms the importance of FCGR-mediated depletion of B cells in autoimmunity. This has implications on the pathology of ITP as well as the immunological effect of B cell depletion. PMID- 22775463 TI - Use of the Peng flap for philtrum reconstruction after surgery for skin cancer: a modified flap technique for philtrum reconstruction. PMID- 22775464 TI - Hantaan virus triggers TLR4-dependent innate immune responses. AB - The innate immune response induced by Hantavirus is responsible for endothelial cell dysfunction and viral pathogenicity. Recent studies demonstrate that TLR4 expression is upregulated and mediates the secretion of several cytokines in Hantaan virus (HTNV)-infected endothelial cells. To examine viral interactions with host endothelial cells and characterize the innate antiviral responses associated with Toll-like receptors, we selected TLR4 as the target molecule to investigate anti-hantavirus immunity. TLR4 mRNA-silenced EVC-304 (EVC-304 TLR4-) cells and EVC-304 cells were used to investigate signaling molecules downstream of TLR4. The expression of the adaptor protein TRIF was higher in HTNV-infected EVC-304 cells than in EVC-304 TLR4- cells. However, there was no apparent difference in the expression of MyD88 in either cell line. The transcription factors for NF-kappaB and IRF-3 were translocated from the cytoplasm into the nucleus in HTNV-infected EVC-304 cells, but not in HTNV-infected EVC-304 TLR4- cells. Our results demonstrate that TLR4 may play an important role in the antiviral immunity of the host against HTNV infection through an MyD88 independent signaling pathway. PMID- 22775465 TI - HLA match in operational tolerance after pediatric living-donor liver transplantation. PMID- 22775466 TI - Intra-articular lornoxicam loaded PLGA microspheres: enhanced therapeutic efficiency and decreased systemic toxicity in the treatment of osteoarthritis. AB - The aim of this study was to investigate the joint tissue distribution and pharmacodynamics of Lornoxicam (Lnxc) following intra-articular injection of either Lnxc suspensions or sustained release Lnxc-loaded PLGA microspheres (Lnxc MS), as well as the biocompatibility of PLGA microspheres with or without drugs. In this study, Lnxc suspensions or Lnxc-loaded PLGA microspheres was injected into the knee joint cavity of rats. Blood samples were taken at predetermined times from the jugular vein and the joint tissue (cartilage and synovial membrane) were removed from the rats. Biocompatibility and pharmacodynamics were evaluated by observing the swelling of the joints of the rats and histological analysis following the injection of the microspheres. The plasma drug concentration decreased in rats and retention time increased in rats' joint with intra-articular injections of microspheres, revealing good targeting efficiency and decreased systemic toxicity. After 30 days of intra-articular injection with Lnxc-loaded or blank microspheres, the filtration liquid accumulation, blood vessels and fibrous proliferation were not detected, showing their good compatibility. Furthermore, the articular cartilage damage by papain could also be repaired by the Lnxc-loaded PLGA microspheres. In conclusion, intra-articular Lnxc-MS have considerable potential for creating a sustained release Lnxc delivery system and providing effective healing to Osteoarthritis. PMID- 22775467 TI - Efficiency of low-level laser therapy in reducing pain induced by orthodontic forces. AB - OBJECTIVE: The aim of this study was to investigate the effect of low-level laser therapy (LLLT) on reducing post-adjustment orthodontic pain via evaluation of gingival crevicular fluid (GCF) composition changes at the level of prostaglandin E(2) (PGE(2)) and visual analogue scale (VAS). BACKGROUND DATA: LLLT has been found to be effective in pain relief. PGE(2) has the greatest impact on the process of pain signals and can be detected in GCF in order to investigate the response of dental and periodontal tissues in a biochemical manner. MATERIALS AND METHODS: Nineteen patients (11 females and 8 males; mean age 13.9 years) were included in this study. Maxillary first molars were banded and then a randomly selected first molar at one side was irradiated (lambda820 nm; continuous wave; output power: 50 mW; focal spot: 0.0314 cm(2); exposure duration: 5 sec; power density: 1.59 W/cm(2); energy dose: 0.25 J; energy density: 7.96 J/cm(2) for each shot), while the molar at the other side was served as placebo control. The GCF was collected from the gingival crevice of each molar to evaluate PGE(2) levels, before band placement, 1 and 24 h after laser irradiation. Pain intensity was analyzed at 5 min, 1 h, and 24 h after band placement by using VAS. RESULTS: Although no difference was found in pain perception at 5 min and 1 h, significant reduction was observed with laser treatment 24 h after application (p<0.05). The mean PGE(2) levels were significantly elevated in control group, whereas a gradual decrease occurred in laser group. The difference in PGE(2) levels at both 1 and 24 h were statistically significant between two groups (p<0.05). CONCLUSIONS: The significant reductions in both pain intensity and PGE(2) levels revealed that LLLT was efficient in reducing orthodontic post-adjustment pain. PMID- 22775468 TI - Role of self-assembled monolayer passivation in electrical transport properties and flicker noise of nanowire transistors. AB - Semiconductor nanowires have achieved great attention for integration in next generation electronics. However, for nanowires with diameters comparable to the Debye length, which would generally be required for one-dimensional operation, surface states degrade the device performance and increase the low-frequency noise. In this study, single In(2)O(3) nanowire transistors were fabricated and characterized before and after surface passivation with a self-assembled monolayer of 1-octadecanethiol (ODT). Electrical characterization of the transistors shows that device performance can be enhanced upon ODT passivation, exhibiting steep subthreshold slope (~64 mV/dec), near zero threshold voltage (~0.6 V), high mobility (~624 cm(2)/V.s), and high on-currents (~40 MUA). X-ray photoelectron spectroscopy studies of the ODT-passivated nanowires indicate that the molecules are bound to In(2)O(3) nanowires through the thiol linkages. Device simulations using a rectangular geometry to represent the nanowire indicate that the improvement in subthreshold slope and positive shift in threshold voltage can be explained in terms of reduced interface trap density and changes in fixed charge density. Flicker (low-frequency, 1/f) noise measurements show that the noise amplitude is reduced following passivation. The interface trap density before and after ODT passivation is profiled throughout the band gap energy using the subthreshold current-voltage characteristics and is compared to the values extracted from the low-frequency noise measurements. The results indicate that self-assembled monolayer passivation is a promising optimization technology for the realization of low-power, low-noise, and fast-switching applications such as logic, memory, and display circuitry. PMID- 22775469 TI - Changes in hematological and serum biochemical parameters in common marmosets (Callithrix jacchus) after inoculation with dengue virus. AB - BACKGROUND: Marmosets are susceptible to dengue virus (DENV) infection. However, blood parameter data and clinical signs of DENV-infected marmosets are limited. METHODS: Blood hematological and serum biochemical values were obtained from twelve DENV-inoculated and four mock-infected marmosets. Additionally, body temperature and activity level were determined. RESULTS: Five DENV-inoculated marmosets demonstrated thrombocytopenia, nine demonstrated leucopenia, and five demonstrated an increase in the levels of AST, ALT, LDH, and BUN. Additionally, seven DENV-inoculated marmosets demonstrated clinical signs including fever and decreases in activity. None of the four mock-inoculated marmosets demonstrated changes in either hematological or biochemical parameters. CONCLUSIONS: Marmosets inoculated with DENV exhibited clinical signs and changes in hematological and biochemical parameters. The results suggest that blood parameter data and clinical signs could potentially be useful markers for understanding the progress of DENV infection in studies using marmosets. PMID- 22775470 TI - Gonadotrophin-releasing hormone signalling downstream of calmodulin. AB - Gonadotrophin-releasing hormone (GnRH) regulates reproduction via binding a G protein coupled receptor on the surface of the gonadotroph, through which it transmits signals, mostly via the mitogen-activated protein (MAPK) cascade, to increase synthesis of the gonadotrophin hormones: luteinising hormone (LH) and follicle-stimulating hormone (FSH). Activation of the MAPK cascade requires an elevation in cytosolic Ca(2+) levels, which is a result of both calcium influx and mobilisation from intracellular stores. However, Ca(2+) also transmits signals via an MAPK-independent pathway, through binding calmodulin (CaM), which is then able to bind a number of proteins to impart diverse downstream effects. Although the ability of GnRH to activate CaM was recognised over 20 years ago, only recently have some of the downstream effects been elucidated. GnRH was shown to activate the CaM-dependent phosphatase, calcineurin, which targets gonadotrophin gene expression both directly and indirectly via transcription factors such as nuclear factor of activated T-cells and Nur77, the Transducer of Regulated CREB (TORC) co-activators and also the prolyl isomerase, Pin1. Gonadotrophin gene expression is also regulated by GnRH-induced CaM-dependent kinases (CaMKs); CaMKI is able to derepress the histone deacetylase-inhibition of beta-subunit gene expression, whereas CaMKII appears to be essential for the GnRH activation of all three subunit genes. Asides from activating gonadotrophin gene expression, GnRH also exerts additional effects on gonadotroph function, some of which clearly occur via CaM, including the proliferation of immature gonadotrophs, which is dependent on calcineurin. In this review, we summarise these pathways, and discuss the additional functions that have been proposed for CaM with respect to modifying GnRH-induced signalling pathways via the regulation of the small GTP-binding protein, Gem, and/or the regulator of G-protein signalling protein 2. PMID- 22775471 TI - Notable effects of metal salts on UV-vis absorption spectra of alpha-, beta-, gamma-, and delta-tocopheroxyl radicals in acetonitrile solution. The complex formation between tocopheroxyls and metal cations. AB - The measurements of the UV-vis absorption spectra of alpha-, beta-, gamma-, and delta-tocopheroxyl (alpha-, beta-, gamma-, and delta-Toc(*)) radicals were performed by reacting aroxyl (ArO(*)) radical with alpha-, beta-, gamma-, and delta-tocopherol (alpha-, beta-, gamma-, and delta-TocH), respectively, in acetonitrile solution including three kinds of alkali and alkaline earth metal salts (LiClO(4), NaClO(4), and Mg(ClO(4))(2)) (MX or MX(2)), using stopped-flow spectrophotometry. The maximum wavelengths (lambda(max)) of the absorption spectra of the alpha-, beta-, gamma-, and delta-Toc(*) located at 425-428 nm without metal salts increased with increasing concentrations of metal salts (0 0.500 M) in acetonitrile and approached some constant values, suggesting (Toc(*)...M(+) (or M(2+))) complex formations. Similarly, the values of the apparent molar extinction coefficient (epsilon(max)) increased drastically with increasing concentrations of metal salts in acetonitrile and approached some constant values. The result suggests that the formations of Toc(*) dimers were suppressed by the metal ion complex formations of Toc(*) radicals. The stability constants (K) were determined for Li(+), Na(+), and Mg(2+) complexes of alpha-, beta-, gamma-, and delta-Toc(*). The K values increased in the order of NaClO(4) < LiClO(4) < Mg(ClO(4))(2), being independent of the kinds of Toc(*) radicals. Furthermore, the K values increased in the order of delta- < gamma- < beta- < alpha-Toc(*) radicals for each metal salt. The alkali and alkaline earth metal salts having a smaller ionic radius of the cation and a larger charge of the cation gave a larger shift of the lambda(max) value, a larger epsilon(max) value, and a larger K value. The result of the DFT molecular orbital calculations indicated that the alpha-, beta-, gamma-, and delta-Toc(*) radicals were stabilized by the (1:1) complex formation with metal cations (Li(+), Na(+), and Mg(2+)). Stabilization energy (E(S)) due to the complex formation increased in the order of Na(+) < Li(+) < Mg(2+) complexes, being independent of the kinds of Toc(*) radicals. The calculated result also indicated that the metal cations coordinate to the O atom at the sixth position of alpha-, beta-, gamma-, and delta-Toc(*) radicals. PMID- 22775472 TI - The preference for potential. AB - When people seek to impress others, they often do so by highlighting individual achievements. Despite the intuitive appeal of this strategy, we demonstrate that people often prefer potential rather than achievement when evaluating others. Indeed, compared with references to achievement (e.g., "this person has won an award for his work"), references to potential (e.g., "this person could win an award for his work") appear to stimulate greater interest and processing, which can translate into more favorable reactions. This tendency creates a phenomenon whereby the potential to be good at something can be preferred over actually being good at that very same thing. We document this preference for potential in laboratory and field experiments, using targets ranging from athletes to comedians to graduate school applicants and measures ranging from salary allocations to online ad clicks to admission decisions. PMID- 22775473 TI - Pranic meditation affects phagocyte functions and hormonal levels of recent practitioners. AB - OBJECTIVES: Despite the recognized importance of phagocytes in the maintenance and recovery of health, the influence of meditation on their functions is not properly established. This investigation aimed at evaluating the influence of pranic meditation on the functions of phagocytes, and on the levels of hormones that influence them. DESIGN: A pre-post design was adopted. SETTING: The investigation was carried out at a university research laboratory. SUBJECTS AND METHODS: Twenty-nine (29) healthy individuals of both sexes, 24-67 years old (median 45), with no previous experience in meditation, received 3-hour-duration weekly training on pranic meditation during 10 weeks and agreed to engage in daily home practice for 20 minutes. Pranic meditation is a novel method of meditation, based on the Vedic tradition, which uses techniques of breathing and visualization for quieting the mind, and for capturing and intentionally directing prana ("vital energy") wherever necessary. For assessing phagocytosis, the production of hydrogen peroxide and nitric oxide by monocytes, and the concentrations of corticotrophin and cortisol, blood was collected at the beginning (week 1), at the middle (week 5), and by the end (week 10) of the practice period. At the same intervals, melatonin concentrations were evaluated in the saliva. RESULTS: Those who meditated for more than 980 minutes showed increased phagocytosis, their monocytes produced higher concentrations of hydrogen peroxide, and their plasma levels of corticotrophin were reduced. The production of nitric oxide by monocytes, and the levels of cortisol and melatonin were not modified by meditation. CONCLUSIONS: This is the first study to show that a short program of pranic meditation practice was able to upregulate the function and metabolism of phagocytes, in parallel with the reduction of the plasma levels of corticotrophin. The results of this study point to a possible causal effect between these events, and indicate that pranic meditation could be useful for stimulating the function and metabolism of phagocytes. PMID- 22775474 TI - Geranylphenazinediol, an acetylcholinesterase inhibitor produced by a Streptomyces species. AB - Geranylphenazinediol (1), a new phenazine natural product, was produced by the Streptomyces sp. strain LB173, which was isolated from a marine sediment sample. The structure was established by analysis of NMR and MS data. 1 inhibited the enzyme acetylcholinesterase in the low micromolar range and showed weak antibacterial activity. In order to get a more detailed picture of the activity profile of 1, its inhibitory potential was compared to that of related structures. PMID- 22775476 TI - History of non-fatal cardiovascular disease in a cohort of Dutch and British patients with haemophilia. AB - OBJECTIVE: Cardiovascular disease (CVD) mortality is reported to be lower in haemophilia patients than in the general population, but information on the occurrence of non-fatal CVD is lacking. The aim of our study was to assess CVD history in a cohort of living haemophilia patients. METHODS: Retrospective data on the occurrence of myocardial infarction, angina pectoris, ischaemic stroke and intracranial bleeding in 709 living Dutch and British haemophilia patients aged 30 yr or older were analysed and compared with the general age-matched male population. RESULTS: There was a trend towards a lower cumulative incidence of myocardial infarction (1.7% vs. 4.0%) and ischaemic stroke (0% vs. 1.5%) in patients with severe haemophilia than in the general population, while the occurrence of angina pectoris was similar (3.2 vs. 3.7%). As expected, the cumulative incidence of intracranial bleeding was, on the other hand, significantly increased in haemophilia patients (1.6% vs. 0.4% in the general population). CONCLUSION: Our results suggest a protective effect of severe haemophilia against acute ischaemic CVD. PMID- 22775475 TI - Factors associated with pathways toward concurrent sex work and injection drug use among female sex workers who inject drugs in northern Mexico. AB - AIMS: To identify factors associated with time to initiation of (i) sex work prior to injecting drugs initiation; (ii) injection drug use prior to sex work initiation; and (iii) concurrent sex work and injection drug use (i.e. initiated at the same age) among female sex workers who currently inject drugs (FSW-IDU). DESIGN: Parametric survival analysis of baseline data for time to initiation event. SETTING: Tijuana and Ciudad Juarez situated on the Mexico-US border. PARTICIPANTS: A total of 557 FSW-IDUs aged >=18 years. MEASUREMENTS: Interview administered surveys assessing context of sex work and injection drug use initiation. FINDINGS: Nearly half (n = 258) initiated sex work prior to beginning to inject, a third (n = 163) initiated injection first and a quarter (n = 136) initiated both sex work and injection drug use concurrently. Low education and living in Ciudad Juarez accelerated time to sex work initiation. Being from a southern Mexican state and initiating drug use with inhalants delayed the time to first injection drug use. Having an intimate partner encourage entry into sex work and first injecting drugs to deal with depression accelerated time to initiating sex work and injection concurrently. Early physical abuse accelerated time to initiating sex work and injection, and substantially accelerated time to initiation of both behaviors concurrently. CONCLUSIONS: Among female sex workers who currently inject drugs in two Mexican-US border cities, nearly half appear to initiate sex work prior to beginning to inject, nearly one-third initiate injection drug use before beginning sex work and one-quarter initiate both behaviors concurrently. Predictors of these three trajectories differ, and this provides possible modifiable targets for prevention. PMID- 22775477 TI - Adverse drug reactions in a population of hospitalized very elderly patients. AB - OBJECTIVES: The aims of the study were to determine the rates, types, severity and preventability of adverse drug reactions (ADRs) in a hospitalized population of very elderly patients (over 80 years of age) and to identify factors that predispose the very elderly to an ADR. METHODS: An observational study was conducted in patients over 80 years of age admitted to four care of the elderly wards in Brighton and Sussex University Hospitals NHS Trust. The main outcome measures were the incidence of ADRs during inpatient stay in older patients and the identification of the major drug classes involved and the risk factors contributing to the occurrence of ADRs. RESULTS: A total of 560 very elderly patients were recruited, 74 of whom experienced one or more ADR (83 in total), representing an incidence of 13.2% (95% CI 10.4, 16). Sixty-three percent of all ADRs were considered preventable, with 57 classified as serious and three as life threatening. The drug classes frequently implicated in ADRs were cardiovascular agents (34%), analgesic medications (18%) and anti-diabetic drugs (10%). Five variables were established as independent predictors of ADRs: number of medications, use of hypoglycaemic agents, history of hyperlipidaemia, raised white cell count on admission, and length of stay. CONCLUSIONS: The ADR incidence reported in this population was no greater than that seen in other studies for both general medical patients and those elderly patients over 65 years of age. A significant proportion of ADRs were preventable, and this suggests that closer monitoring of high-risk elderly patients is needed to address this problem. PMID- 22775479 TI - Placebo controlled evaluation of Xilei San, a herbal preparation in patients with intractable ulcerative proctitis. AB - BACKGROUND AND AIM: Topical mesalamine or corticosteroid has shown efficacy in patients with ulcerative proctitis, but patients often become refractory to these interventions. Xilei San is a herbal preparation with evidence of anti inflammatory effects. We evaluated the efficacy of topical Xilei San in ulcerative proctitis patients. METHODS: In a double blind setting, 30 patients with intractable ulcerative proctitis despite >= 4 weeks of topical mesalamine or corticosteroid were randomly assigned to True (n = 15) and placebo (n = 15). Patients in True received suppository Xilei San (0.1 g/dose per day of Xilei San), the other 15 received placebo suppository. The initial efficacy was evaluated on day 14. Primary endpoint of the trial was avoiding relapse during 180 days, relapse meant recurrence of active disease. Riley's index was applied for endoscopic and histological evaluations, while patients' quality of life was evaluated by an inflammatory bowel disease questionnaire. RESULTS: On day 14, the number of patients who achieved remission, clinical activity index <= 4 in True was significantly higher versus placebo (P < 0.04). Likewise, at day 180, an 81.8% of patients in True were without relapse versus 16.7% in placebo (P < 0.001). Further, significant endoscopic (P < 0.01), histological (P < 0.02) and inflammatory bowel disease questionnaire (P < 0.04) improvements were observed in True, but not in placebo. CONCLUSIONS: This is the first controlled investigation showing significant clinical and endoscopic efficacy for Xilei San in patients with intractable ulcerative proctitis. Topical Xilei San was well tolerated, and was without safety concerns. PMID- 22775480 TI - Dye bonding to TiO2: in situ attenuated total reflection infrared spectroscopy study, simulations, and correlation with dye-sensitized solar cell characteristics. AB - Processing dye-sensitized solar cells gains more and more importance as interest in industrial applications grows daily. For large-scale processing and optimizing manufacturing in terms of environmental acceptability as well as time and material saving, a detailed knowledge of certain process steps is crucial. In this paper we concentrate on the sensitizing step of production, i.e., the anchoring of the dye molecules onto the TiO(2) semiconductor. A vacuum-tight attentuated total reflection infrared (ATR-IR) flow-through cell was developed, thus allowing measurements using a vacuum spectrometer to monitor infiltration of dye molecules into the porous TiO(2) film in situ at high sensitivity. In particular, the influence of the anchor and backbone of perylene dye molecules as well as the influence of solvents on the adsorption process was investigated. The experiments clearly show that an anhydride group reacts much slower than an acid group. A significantly lower amount of anhydride dye can be adsorbed on the films. Ex situ transmission experiments furthermore indicate that the availability of OH groups on the TiO(2) surface may limit dye adsorption. Also the backbone and base frame of the dye can influence the adsorption time drastically. Electrical cell characteristics correlate with the amount of adsorbed dye molecules determined by in situ ATR-IR measurements. The latter is also sensitive toward the diffusion of the dye through the porous layer. To gain a deeper understanding of the interplay between diffusion and adsorption, simulations were performed that allowed us to extract diffusion and adsorption constants. Again it was demonstrated that the anchoring group has a strong effect on the adsorption rate. The influence of the solvent was also studied, and it was found that both adsorption and desorption are affected by the solvent. Protic polar solvents are able to remove bound dye molecules, which is a possible pathway of cell degradation. Most importantly, the analysis shows the potential of this approach for the evaluation of molecules or additives concerning their characteristics important for cell processing. PMID- 22775478 TI - Inappropriate prescribing of proton pump inhibitors in older patients: effects of an educational strategy. AB - BACKGROUND: An increasing number of older patients are prescribed proton pump inhibitors (PPIs). However, the extent of inappropriate PPI prescribing in this group is largely unknown. OBJECTIVE: We sought to identify clinical and demographic factors associated with inappropriate PPI prescribing in older patients and to assess the effects of a targeted educational strategy in a controlled hospital environment. METHODS: Clinical and demographic characteristics and full medication exposure on admission were recorded in 440 consecutive older patients (mean +/- SD age 84 +/- 7 years) admitted to a teaching hospital between 1 February 2011 and 30 June 2011. A 4-week educational strategy to reduce inappropriate PPI prescribing during hospital stay, either by stopping or reducing PPI doses, was conducted within the study period. The main outcome measures of the study were the incidence of inappropriate PPI prescribing and the effects of interventions to reduce it. RESULTS: On admission, PPIs were established therapy in 164 patients (37%). This was considered inappropriate in 100 patients (61%). Lower Charlson Comorbidity Index score (odds ratio [OR] 0.76; 95% CI 0.57, 0.94; p = 0.006) and history of dementia (OR 1.65; 95% CI 1.28, 1.83; p = 0.005) were independently associated with inappropriate PPI prescribing. Interventions to reduce inappropriate PPI prescribing occurred more frequently during and after the education phase (frequency of interventions in patients with inappropriate PPI prescribing: pre-education phase 9%, during education phase 43%, and post-education phase 46%, p = 0.006). Prescribing interventions were not associated with acid rebound symptoms. CONCLUSIONS: Inappropriate PPI prescribing in older patients is frequent and independently associated with co-morbidities and dementia. A targeted in-hospital educational strategy can significantly and safely reduce inappropriate PPI prescribing in the short term. PMID- 22775481 TI - Effects of tibolone or continuous combined oestradiol/norethisterone acetate on glucose and insulin metabolism. AB - OBJECTIVE: To determine the effects of tibolone or oestradiol (E(2) )/norethisterone acetate (NETA) hormone replacement therapy on glucose and insulin metabolism in postmenopausal women. DESIGN: Single-centre double-blind placebo-controlled randomized clinical trial. SUBJECTS/METHODS: We randomized 105 healthy postmenopausal women to tibolone 2.5 mg daily, continuous combined oral E(2) 2 mg/NETA 1 mg daily or placebo over a 2-year study. We performed intravenous glucose tolerance tests (IVGTT) with measurements of plasma glucose, insulin and C-peptide concentrations and the IVGTT glucose elimination rate, k. Mathematical modelling was performed to determine measures of insulin sensitivity, S(i) , pancreatic insulin secretion and hepatic and plasma insulin elimination. RESULTS: Tibolone decreased S(i) to 53-63% and k to 72-79% of baseline values but increased IVGTT phase 2 C-peptide concentrations 1.6-1.8-fold and pancreatic insulin secretion 2.2-2.4-fold, so overall IVGTT glucose concentrations were unaffected. Similar, but for k, significantly smaller changes in insulin and C-peptide secretion were seen with E(2) /NETA, also with no effect on overall IVGTT glucose concentrations. CONCLUSIONS: Tibolone reduces insulin sensitivity. Healthy postmenopausal women seem able to compensate for this and maintain normal postload glucose concentrations, but it may not be advisable to prescribe tibolone to women with, or at increased risk for, diabetes. PMID- 22775482 TI - Local and systemic regulation of sulfur homeostasis in roots of Arabidopsis thaliana. AB - Nutrients are limiting for plant growth and vigour. Hence, nutrient uptake and homeostasis must be adjusted to the needs of the plant according to developmental stages and environmental conditions. A split-root system was applied to analyse the systemic and local response of Arabidopsis thaliana to sulfur starvation. Arabidopsis thaliana plants in which only one root half was starved while the other root half was supplied with sulfate were analysed at the metabolic and transcriptional level. No systemic induction of sulfate uptake or expression of sulfate starvation marker genes was observed in split-roots sufficiently supplied with sulfate. Our data suggest that no activation of sulfur uptake takes part in sulfur-supplied root patches when the general sulfur status declines. When comparing roots of fully sulfate-starved plants with sulfate-starved split-root roots, expression of several potentially OAS responsive genes was attenuated in split-roots depending on the shoot sulfate status and the local root O acetylserine concentration. In contrast, high-affinity sulfate transporters displayed similar expression in sulphate-starved split-roots and the corresponding controls. Feeding of (35) SO(4) (2-) to the shoot or to either part of a split-root system revealed that sulfate is the most prominent mobile sulfur containing compound within the plant. Hence, we postulate a model whereby the soil sulfate availability regulates the sulfate uptake system of roots while the shoot sulfur status modulates the local O-acetylserine response in the root by passive 'plant sulfur status-dependent' transport of sulfate. PMID- 22775483 TI - Genetic heterogeneity in Pakistani microcephaly families. AB - Autosomal recessive primary microcephaly (MCPH) is caused by mutations in at least eight different genes involved either in cell division or DNA repair. Most mutations are identified in consanguine families from Pakistan, Iran and India. To further assess their genetic heterogeneity and mutational spectra, we have analyzed 57 consanguine Pakistani MCPH families. In 34 MCPH families, we detected linkage to five out of the eight well-characterized disease loci and identified mutations in 27 families, leaving seven families without mutations in the coding exons of the presumably underlying MCPH genes. In the MCPH cohort 23 families could not be linked to any of the known loci, pointing to remarkable locus heterogeneity. The majority of mutations were found in ASPM followed by WDR62, CENPJ, CEP152 and MCPH1. One ASPM mutation (p.Trp1326*) was found in as many as eight families suggesting a Pakistani founder mutation. One third of the families were linked to ASPM followed by WDR62 confirming previous data. We identified three novel ASPM mutations, four novel WDR62 mutations, one novel MCPH1 mutation and two novel CEP152 mutations. CEP152 mutations have not been described before in the Pakistani population. PMID- 22775484 TI - alpha1,3-galactosyltransferase deficiency in germ-free miniature pigs increases N glycolylneuraminic acids as the xenoantigenic determinant in pig-human xenotransplantation. AB - In this study, we examined whether Hanganutziu-Deicher (H-D) antigens are important as an immunogenic non-alpha1,3-galactose (Gal) epitope in pigs with a disrupted alpha1,3-galactosyltransferase gene. The targeting efficiency of the AO blood genotype was achieved (2.2%) in pig fibroblast cells. A total of 1800 somatic cell nuclear transfer (SCNT) embryos were transferred to 10 recipients. One recipient developed to term and naturally delivered two piglets. The alpha1,3 galactosyltransferase activity in lung, liver, spleen, and testis of heterozygote alpha1,3-galactosyltransferase gene knockout (GalT-KO) pigs was significantly decreased, whereas brain and heart showed very low decreasing levels of alpha1,3 galactosyltransferase activity when compared to those of control. Enzyme-linked lectinosorbent assay showed that the heterozygote GalT-KO pig had more sialylalpha2,6- and sialylalpha2,3-linked glycan than the control. Furthermore, the heart, liver, and kidney of the heterozygote GalT-KO pig had a higher N glycolylneuraminic acid (Neu5Gc) content than the control, whereas the lung of the heterozygote GalT-KO pig had Neu5Gc content similar to the control. Collectively, the data strongly indicated that Neu5Gc is a more critical xenoantigen to overcoming the next acute immune rejection in pig to human xenotransplantation. PMID- 22775485 TI - Good advice from the deputy editors of Medical Education. PMID- 22775486 TI - Dealing with the uncertain risk of variant Creutzfeldt-Jakob disease transmission by coagulation replacement products. AB - The identification of variant Creutzfeldt-Jakob disease (vCJD) in the UK in 1996 led to significant concerns about the possibility of secondary transmission, however the prevalence of subclinical vCJD and risks of vCJD transmission by plasma are not known. In the UK, public health precautions have been implemented in all recipients of coagulation factor concentrates manufactured from UK plasma pools between 1980 and 2001. The recent demonstration of abnormal prion protein in a spleen sample at autopsy of a UK haemophilic patient who received coagulation factor concentrates to which a donor incubating vCJD had contributed most likely represents the first case of vCJD transmission by coagulation factor concentrates. We review the uncertainties that surround risk of vCJD transmission by coagulation factor concentrates, the challenges in dealing with undefined risks, the rationale behind current policies and the implementation of vCJD surveillance and risk management measures in bleeding disorder patients in the UK. PMID- 22775487 TI - Hospitalization for physical illness and risk of subsequent suicide: a population study. AB - OBJECTIVE: To examine suicide risk in relation to physical illness across a broad range of illnesses, including hospitalization history, specific organ or system illness and comorbidity. DESIGN: A nested case-control study. SETTING: Data were retrieved from five Danish national registers. SUBJECTS: On the basis of the entire population of Denmark, this study included 27 262 suicide cases, and 468 007 live controls matched for sex and date of birth. MAIN OUTCOME MEASURES: Risk of suicide was assessed using conditional logistic regression. RESULTS: In the study population, 63.5% of suicide cases and 44.5% of comparison controls had a history of hospitalization for physical illness. A physical illness significantly increased the risk of subsequent suicide (incidence rate ratios 2.13, 95% CI 2.07 2.18) with a substantially greater effect in women than in men (P < 0.01). The elevated risk increased progressively with frequency and recency of hospitalization and was significant for diseases occurring in all organs or systems of the body. Comorbidity involving several organs or systems increased the risk substantially. The associated estimates were to some extent reduced but remained highly significant after adjustment for psychiatric history and socio economic status. Taking into account both prevalence and adjusted effect size, physical illness accounted for 24.4%, 21.0% and 32.3% of population attributable risk for suicide in total, male and female populations, respectively. CONCLUSIONS: Physical illness constitutes a significant risk factor for suicide independent of psychiatric and socio-economic factors. Clinicians treating physically ill patients should be aware of the risk, especially amongst those with multiple or recent hospitalizations, or multiple comorbidities. PMID- 22775488 TI - The carbonate-silicate cycle and CO2/climate feedbacks on tidally locked terrestrial planets. AB - Atmospheric gaseous constituents play an important role in determining the surface temperatures and habitability of a planet. Using a global climate model and a parameterization of the carbonate-silicate cycle, we explored the effect of the location of the substellar point on the atmospheric CO(2) concentration and temperatures of a tidally locked terrestrial planet, using the present Earth continental distribution as an example. We found that the substellar point's location relative to the continents is an important factor in determining weathering and the equilibrium atmospheric CO(2) level. Placing the substellar point over the Atlantic Ocean results in an atmospheric CO(2) concentration of 7 ppmv and a global mean surface air temperature of 247 K, making ~30% of the planet's surface habitable, whereas placing it over the Pacific Ocean results in a CO(2) concentration of 60,311 ppmv and a global temperature of 282 K, making ~55% of the surface habitable. PMID- 22775489 TI - Effect of 635 nm light-emitting diode irradiation on intracellular superoxide anion scavenging independent of the cellular enzymatic antioxidant system. AB - OBJECTIVE: The aim of this study was to examine the reactive oxygen species (ROS) that are dissipated by 635 nm irradiation, and the effect of 635 nm irradiation on ROS scavenging system. BACKGROUND DATA: Intracellular ROS are produced in the form of superoxide anion by either nicotinamide adenine dinucleotide phosphate (NADPH) oxidase or xanthine oxidase in response to a number of stimuli. Low-level light irradiation decreases the intracellular ROS level and has been used in clinical situations for reducing the level of oxidative stress. METHODS: Human epithelial cells were exposed to exogenous and endogenous oxidizing agents that promote the generation of harmful ROS. These were then irradiated with 635 nm LED light, 5 mW/cm(2) for 1 h, 18 J/cm(2) or by 470 nm LED light, also 5 mW/cm(2) for 1 h, 18 J/cm(2) on a 9 cm cell culture dish. After irradiation, the MTT reduction method and malondialdehyde (MDA) colorimetric assay were performed in xanthine/xanthine oxidase (XXO)- or hydrogen peroxide (H(2)O(2))-treated HaCaT cells. The superoxide anion was detected by an electron spin resonance (ESR) spectrometer using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the spin trap and H(2)O(2) was assayed by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCF-DA). RESULTS: Irradiation at 635 nm enhanced cell viability in the XXO-treated HaCaT cells. Also, irradiation had a much lesser effect on cell viability in the HaCaT cells treated with exogenous H(2)O(2) as compared with that in cells treated with N-acetyl-L-cysteine. The level of the superoxide anion increased in response to XXO treatment, and then decreased after 635 nm irradiation. Irradiation with 635 nm led to a decrease in superoxide anion and lipid peroxidation levels in the presence or absence of diethyldithiocarbamate. CONCLUSIONS: These results highlight the potential role of 635 nm irradiation in protection against oxidative stress by scavenging superoxide anions. Also, a pathway that is independent of the activities of intracellular enzymatic ROS scavengers, such as superoxide dismutase, glutathione peroxidase and catalase might be involved in its mechanism of action. PMID- 22775490 TI - Bioactivation of chlorpyrifos by CYP2B6 variants. AB - Chlorpyrifos (CPF), an organophosphorus (OP) pesticide, is bioactivated by cytochrome P450s (CYPs) to the active metabolite chlorpyrifos oxon (CPF-O). Given that human CYP2B6 has the highest intrinsic clearance (CL(int)) for CPF bioactivation, CYP2B6 polymorphisms may impact human susceptibility to CPF at real world environmental and occupational CPF exposure levels. CYP2B6.4,.5,.7, and .18 were over-expressed in mammalian COS-1 cells to assess the impact of CYP2B6 variants on the K(m) and V(max) for bioactivation of CPF. Cell lysates were incubated with CPF (0-100 MUM) and the production of CPF-O was measured via HPLC analysis. CYP2B6 content was determined by western blot. CYP2B6.18 had neither detectable protein nor activity levels. The V(max) value for each remaining variant was significantly higher than wild-type (CYP2B6.1, V(max) 4.13 * 10(4) pmol/min/nmol CYP2B6), with CYP2B6.4,.5, and .7 having V(max) values of 4.52 * 10(5), 1.82 * 10(5), and 9.60 * 10(4) pmol/min/nmol CYP2B6, respectively. The K(m) values for these variants ranged from 0.39 to 1.09 MUM and were not significantly different from wild-type. All active variants examined had significantly higher CL(int) than CYP2B6.1. Variants of CYP2B6 have altered capacity to bioactivate CPF and may affect individual susceptibility by altering the V(max) for CPF-O formation. PMID- 22775491 TI - Isoreticular two-dimensional covalent organic frameworks synthesized by on surface condensation of diboronic acids. AB - On-surface self-condensation of 1,4-benzenediboronic acid was previously shown to yield extended surface-supported, long-range-ordered two-dimensional covalent organic frameworks (2D COFs). The most important prerequisite for obtaining high structural quality is that the polycondensation (dehydration) reaction is carried out under slightly reversible reaction conditions, i.e., in the presence of water. Only then can the subtle balance between kinetic and thermodynamic control of the polycondensation be favorably influenced, and defects that are unavoidable during growth can be corrected. In the present study we extend the previously developed straightforward preparation protocol to a variety of para-diboronic acid building blocks with the aim to tune lattice parameters and pore sizes of 2D COFs. Scanning tunneling microscopy is employed for structural characterization of the covalent networks and of noncovalently self-assembled structures that form on the surface prior to the thermally activated polycondensation reaction. PMID- 22775493 TI - Measuring the patient health, societal and economic benefits of US pediatric therapeutics legislation. AB - Through at least the mid-1990s, children were often referred to as 'therapeutic orphans' for whom many treatments were administered without the benefit of appropriate studies to guide drug labeling for dosing and other critical therapeutic decisions. At that time, there were no incentives for manufacturers to pursue such work, nor regulatory requirements to compel these studies. Congress addressed this by including an important provision titled the Best Pharmaceuticals for Children Act (BPCA) in the 1997 Food and Drug Administration Modernization and Accountability Act. This was complemented by another key piece of legislation, the Pediatric Research Equity Act (PREA) in 2003. The former Act and its successors created an incentive for firms to study on-patent drugs in pediatric populations by extending the market exclusivity of a medicine by 6 months. The latter was a requirement that provided the US FDA with the authority to require studies of drugs in children if an adult indication also occurs in children. In the current paper, we consider the effects of both pieces of legislation in terms of the health, societal, and economic benefits they have likely imparted and will continue to provide in the future. We conclude that the gains have been substantial - both in terms of safer and more effective use of medicines in children and in terms of new research that has been incentivized by the BPCA exclusivity provision. We estimate the gross economic benefits from the latter alone to be approximately $US360 billion. PMID- 22775494 TI - Spheres growing on a sphere: a model to predict the morphology yields of colloidal molecules obtained through a heterogeneous nucleation route. AB - Through the heterogeneous nucleation of polymer nodules on a surface-modified silica particle, the high-yield achievement of hybrid colloidal molecules with a well-controlled multipod-like morphology was recently demonstrated. However, as the formation mechanism of these colloidal molecules has not been completely understood yet, some opportunities remain to reduce the tedious empirical process needed to optimize the chemical recipes. In this work, we propose a model to help understand the formation mechanism of almost pure suspensions of well-defined colloidal molecules. The outcomes of the model allow proposing probable nucleation growth scenario able to explain the experimental results. Such a model should make easier the determination of the optimal recipe parameters for a targeted morphology. The reasonably good agreements between the model and the experimental results show that the most important processes have been captured. It is thus a first step toward the rational design of large quantities of chemically prepared colloidal molecules. PMID- 22775495 TI - A review of corneal melting following kerato-refractive surgery. AB - Corneal melting is a rare complication that may occur following a number of different types of surgery. Keratolysis may lead to scarring, irregular astigmatism, photophobia and decreased vision. This article reviews the incidence, pathophysiology and treatment of this condition in kerato-refractive surgery. PMID- 22775497 TI - An accuracy-response time capacity assessment function that measures performance against standard parallel predictions. AB - Measures of human efficiency under increases in mental workload or attentional limitations are vital in studying human perception, cognition, and action. Assays of efficiency as workload changes have typically been confined to either reaction times (RTs) or accuracy alone. Within the realm of RTs, a nonparametric measure called the workload capacity coefficient has been employed in many studies (Townsend & Nozawa, 1995). However, the contribution of correct versus incorrect responses has been unavailable in that context. A nonparametric statistic that is capable of simultaneously taking into account accuracy as well as RTs would be highly useful. This theoretical study develops such a tool for two important decisional stopping rules. Preliminary data from a simple visual identification study illustrate one potential application. PMID- 22775498 TI - Social class, solipsism, and contextualism: how the rich are different from the poor. AB - Social class is shaped by an individual's material resources as well as perceptions of rank vis-a-vis others in society, and in this article, we examine how class influences behavior. Diminished resources and lower rank create contexts that constrain social outcomes for lower-class individuals and enhance contextualist tendencies--that is, a focus on external, uncontrollable social forces and other individuals who influence one's life outcomes. In contrast, abundant resources and elevated rank create contexts that enhance the personal freedoms of upper-class individuals and give rise to solipsistic social cognitive tendencies--that is, an individualistic focus on one's own internal states, goals, motivations, and emotions. Guided by this framework, we detail 9 hypotheses and relevant empirical evidence concerning how class-based contextualist and solipsistic tendencies shape the self, perceptions of the social environment, and relationships to other individuals. Novel predictions and implications for research in other socio-political contexts are considered. PMID- 22775500 TI - Bayesian analogy with relational transformations. AB - How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy problems. We introduce Bayesian analogy with relational transformations (BART) and apply the model to the task of learning first-order comparative relations (e.g., larger, smaller, fiercer, meeker) from a set of animal pairs. Inputs are coded by vectors of continuous valued features, based either on human magnitude ratings, normed feature ratings (De Deyne et al., 2008), or outputs of the topics model (Griffiths, Steyvers, & Tenenbaum, 2007). Bootstrapping from empirical priors, the model is able to induce first-order relations represented as probabilistic weight distributions, even when given positive examples only. These learned representations allow classification of novel instantiations of the relations and yield a symbolic distance effect of the sort obtained with both humans and other primates. BART then transforms its learned weight distributions by importance-guided mapping, thereby placing distinct dimensions into correspondence. These transformed representations allow BART to reliably solve 4-term analogies (e.g., larger:smaller::fiercer:meeker), a type of reasoning that is arguably specific to humans. Our results provide a proof-of-concept that structured analogies can be solved with representations induced from unstructured feature vectors by mechanisms that operate in a largely bottom-up fashion. We discuss potential implications for algorithmic and neural models of relational thinking, as well as for the evolution of abstract thought. PMID- 22775503 TI - The spotlight of attention illuminates failed feature-based expectancies. AB - A well-replicated finding is that visual stimuli presented at an attended location are afforded a processing benefit in the form of speeded reaction times and increased accuracy (Mangun, ; Posner,). This effect has been described using a spotlight metaphor, in which all stimuli within the focus of spatial attention receive facilitated processing, irrespective of other stimulus parameters. However, the spotlight metaphor has been brought into question by a series of combined expectancy studies that demonstrated that the behavioral benefits of spatial attention are contingent on secondary feature-based expectancies (Kingstone,). The present work used an event-related potential (ERP) approach to reveal that the early neural signature of the spotlight of spatial attention is not sensitive to the validity of secondary feature-based expectancies. PMID- 22775501 TI - Principles of contour information: Reply to Lim and Leek (2012). AB - Lim and Leek (2012) presented a formalization of information along object contours, which they argued was an alternative to the approach taken in our article (Feldman & Singh, 2005). Here, we summarize the 2 approaches, showing that--notwithstanding Lim and Leek's (2012) critical rhetoric--their approach is substantially identical to ours, except for the technical details of the formalism. Following the logic of our article point by point, Lim and Leek (a) defined probabilistic expectations about the geometry of smooth contours (which they based on differential contour geometry, while we used a discrete approximation--the only essential difference in their approach), (b) assumed that information along the contour was proportional to the negative logarithm of probability, following standard information theory, and then (c) extended this formulation to closed contours. We analyze what they described as errors in our approach, all of which rest on mathematical misunderstandings or bizarre misreadings of our article. We also show that their extension to 3-dimensional surfaces and their "modified minima rule" contain fatal deficiencies. PMID- 22775499 TI - Generalization through the recurrent interaction of episodic memories: a model of the hippocampal system. AB - In this article, we present a perspective on the role of the hippocampal system in generalization, instantiated in a computational model called REMERGE (recurrency and episodic memory results in generalization). We expose a fundamental, but neglected, tension between prevailing computational theories that emphasize the function of the hippocampus in pattern separation (Marr, 1971; McClelland, McNaughton, & O'Reilly, 1995), and empirical support for its role in generalization and flexible relational memory (Cohen & Eichenbaum, 1993; Eichenbaum, 1999). Our account provides a means by which to resolve this conflict, by demonstrating that the basic representational scheme envisioned by complementary learning systems theory (McClelland et al., 1995), which relies upon orthogonalized codes in the hippocampus, is compatible with efficient generalization-as long as there is recurrence rather than unidirectional flow within the hippocampal circuit or, more widely, between the hippocampus and neocortex. We propose that recurrent similarity computation, a process that facilitates the discovery of higher-order relationships between a set of related experiences, expands the scope of classical exemplar-based models of memory (e.g., Nosofsky, 1984) and allows the hippocampus to support generalization through interactions that unfold within a dynamically created memory space. PMID- 22775505 TI - Primary events in the blue light sensor plant cryptochrome: intraprotein electron and proton transfer revealed by femtosecond spectroscopy. AB - Photoreceptors are chromoproteins that undergo fast conversion from dark to signaling states upon light absorption by the chromophore. The signaling state starts signal transduction in vivo and elicits a biological response. Therefore, photoreceptors are ideally suited for analysis of protein activation by time resolved spectroscopy. We focus on plant cryptochromes which are blue light sensors regulating the development and daily rhythm of plants. The signaling state of these flavoproteins is the neutral radical of the flavin chromophore. It forms on the microsecond time scale after light absorption by the oxidized state. We apply here femtosecond broad-band transient absorption to early stages of signaling-state formation in a plant cryptochrome from the green alga Chlamydomonas reinhardtii. Transient spectra show (i) subpicosecond decay of flavin-stimulated emission and (ii) further decay of signal until 100 ps delay with nearly constant spectral shape. The first decay (i) monitors electron transfer from a nearby tryptophan to the flavin and occurs with a time constant of tau(ET) = 0.4 ps. The second decay (ii) is analyzed by spectral decomposition and occurs with a characteristic time constant tau(1) = 31 ps. We reason that hole transport through a tryptophan triad to the protein surface and partial deprotonation of tryptophan cation radical hide behind tau(1). These processes are probably governed by vibrational cooling. Spectral decomposition is used together with anisotropy to obtain the relative orientation of flavin and the final electron donor. This narrows the number of possible electron donors down to two tryptophans. Structural analysis suggests that a set of histidines surrounding the terminal tryptophan may act as proton acceptor and thereby stabilize the radical pair on a 100 ps time scale. PMID- 22775504 TI - Induction of palate epithelial mesenchymal transition by transforming growth factor beta3 signaling. AB - Transforming growth factor (TGFbeta)3 is essential for palate development, particularly during the late phase of palatogenesis when the disintegration of the palatal medial edge seam (MES) occurs resulting in mesenchymal confluence. The MES is composed of medial-edge epithelium (MEE) of opposite palatal shelves; its complete disintegration is essential for mediating correct craniofacial morphogenesis. This phenomenon is initiated by TGFbeta3 upon adherence of opposing palatal shelves, and subsequently epithelial-mesenchymal transition (EMT) instigates the loss of E-Cadherin, causing the MES to break into small epithelial islands forming confluent palatal mesenchyme; however, apoptosis and cell migration or in combination of all are other established mechanisms of seam disintegration. To investigate the molecular mechanisms that cause this E Cadherin loss, we isolated and cultured murine embryonic primary MES cells from adhered palates and employed several biological approaches to explore the mechanism by which TGFbeta3 facilitates palatal seam disintegration. Here, we demonstrate that TGFbeta3 signals by activating both Smad-dependent and Smad independent pathways. However, activation of the two most common EMT related transcription factors, Snail and SIP, was facilitated by Smad-independent pathways, contrary to the commonly accepted Smad-dependent pathway. Finally, we provide the first evidence that TGFbeta3-activated Snail and SIP1, combined with Smad4, bind to the E-Cadherin promoter to repress its transcription in response to TGFbeta3 signaling. These results suggest that TGFbeta3 uses multiple pathways to activate Snail and SIP1 and these transcription factors repress the cell-cell adhesion protein, E-Cadherin, to induce palatal epithelial seam EMT. Manipulation and intervention of the pathways stimulated by TGFbeta3 during palate development may have a significant therapeutic potential. PMID- 22775507 TI - Bevacizumab treatment of prostate cancer. AB - INTRODUCTION: Angiogenesis plays an important role in the development and progression of prostate cancer. Vascular endothelial growth factor (VEGF) is a primary mediator of this process and is a target for novel therapies. Bevacizumab is a recombinant anti-VEGF monoclonal antibody that has demonstrated antitumor activity in a variety of cancers. AREAS COVERED: In this review, we present the results of several clinical trials for bevacizumab in prostate cancer. Overall, these trials have shown improvements in progression-free survival but no changes in overall survival. Ongoing clinical trials are testing bevacizumab in combination with novel cytotoxic drugs and targeted therapies in metastatic and localized settings. EXPERT OPINION: Bevacizumab has biological activity in prostate cancer. However, the mixed clinical trial results support the theory that prostate cancers may be driven only in part by angiogenesis. Questions remain about the future role of bevacizumab in the treatment of prostate cancer. PMID- 22775506 TI - Allelic variants of XRCC1 and XRCC3 repair genes and susceptibility of oral cancer in Brazilian patients. AB - BACKGROUND: The capacity for DNA repair is essential in maintaining cellular functions and homeostasis; however, this capacity can be altered based on DNA sequence variations in DNA repair genes, which may contribute to the onset of cancer. Many single-nucleotide polymorphisms (SNPs) in repair genes have been found to be associated with oral cancer. The aim of this study was to investigate the relationship between the presence of allelic variants Arg194Trp (rs:1799782) and Arg399Gln (rs: 25487) of XRCC1 gene and Thr241Met (rs: 861539) of XRCC3 gene and susceptibility to oral cancer. We also attempted to correlate the frequencies obtained for each of the SNPs to histopathological parameters. METHODS: A case control study was conducted with genomic DNA from 150 patients with oral squamous cell carcinomas and 150 controls. SNPs were genotyped by RFLP-PCR. RESULTS: The presence of the polymorphic variants of the XRCC1 gene within codon 194 (OR 0.82, 95% CI: 0.44-1.51) and codon 399 (OR 0.94, 95% CI: 0.59-1.50) and within the XRCC3 gene (OR 0.72; 95% CI: 0.45-1.16) were not associated with an increased risk of oral cancer. A combinational analysis of SNPs in both genes indicated no association. The presence of the allelic variants of these two genes had no statistically significant effect on tumor differentiation, lymph node invasion or tumor size. CONCLUSIONS: These results suggest that allelic variants of XRCC1 and XRCC3 are not suitable markers for susceptibility to carcinomas of the oral cavity and are also not related to the later stages of such tumors. PMID- 22775509 TI - Influence of stem-cell cycle time on accelerated re-population during radiotherapy in head and neck cancer. AB - OBJECTIVES: Tumour re-population during radiotherapy was identified as an important reason for treatment failure in head and neck cancers. The process of re-population is suggested to be caused by various mechanisms, one of the most plausible one being accelerated division of stem-cells (i.e. drastic shortening of cell cycle duration). However, the literature lacks quantitative data regarding the length of tumour stem-cell cycle time during irradiation. MATERIALS AND METHODS: The presented work suggests that if accelerated stem-cell division is indeed a key mechanism behind tumour re-population, the stem-cell cycle time can drop below 10 h during radiotherapy. To illustrate the possible implications, the mechanism of accelerated division was implemented into a Monte Carlo model of tumour growth and response to radiotherapy. Tumour response to radiotherapy was simulated with different stem-cell cycle times (between 2 and 10 h) after the initiation of radiotherapy. RESULTS: It was found that very short stem-cell cycle times lead to tumour re-population during treatment, which cannot be overcome by radiation-induced cell kill. Increasing the number of radiation dose fractions per week might be effective, but only for longer cell cycle times. CONCLUSION: It is of crucial importance to quantitatively assess the mechanisms responsible for tumour re-population, given that conventional treatment regimens are not efficient in delivering lethal doses to advanced head and neck tumours. PMID- 22775508 TI - Risk of injury after alcohol consumption from case-crossover studies in five countries from the Americas. AB - AIMS: This study aimed to: (i) provide relative risk (RR) estimates between acute alcohol use and injuries from emergency departments (EDs) in the Dominican Republic, Guatemala, Guyana, Nicaragua and Panama, and (ii) test whether the RR differs if two control periods for the estimates were used. DESIGN: Case crossover methodology was used to obtain estimates of the RR of having an injury within 6 hours after drinking alcohol, using a pair-matching design with control periods of the same time of day on the day prior to injury, and the same time of day and day of week during the week prior to injury. SETTING: EDs. PARTICIPANTS: A total of 2503 injured patients from EDs were interviewed between 2010 and 2011, with a response rate of 92.6%. MEASUREMENTS: Number of drinks consumed within 6 hours prior to the injury and in the two control periods. FINDINGS: The RR of injury after drinking alcohol was 4.38 [95% confidence interval (CI): 3.29-5.84] using the prior week as the control period, and 5.35 (CI: 3.50-8.17) using the prior day as a control period. The RR was 5.08 (CI: 4.15-6.23) in multiple matching. Those drinking one to two drinks had a RR of 4.85 (CI: 3.12-7.54); those drinking three to five drinks an RR of 5.00 (CI: 3.47-7.18); those drinking six to 15 drinks an RR of 4.54 (CI: 3.36-6.14); and those drinking 16 or more drinks an RR of 10.42 (CI: 4.38-24.79). CONCLUSIONS: As in other countries, drinking alcohol is an important trigger for an injury in the Dominican Republic, Guatemala, Guyana, Nicaragua and Panama. PMID- 22775510 TI - The syntheses and electrochemical studies of a ferrocene substituted diiminopyridine ligand and its P, S, Se, and Te complexes. AB - A new reversible, redox active diiminopyridine ligand (1Fc) containing pendant ferrocene functionalities was isolated and fully characterized. The reaction of 1Fc with chalcogen pseudohalides of sulfur, selenium, and tellurium yielded the respective N,N',N"-chelated chalcogen dications. Phosphorus chemistry proceeded in a related manner but, in this case, by the direct addition of 1Fc with PI(3) to yield the N,N',N"-chelated P(I) cation. These species represent the first synthesized main group complexes involving a redox active diiminopyridine ligand containing pendant ferrocenes. Electrochemical studies of the free ligand shows a reversible two-electron process. The chelated phosphorus cation, however, displayed three events, the first being a quasi-reversible two-electron process, involving the oxidation at the P(I) center, resulting in a P(III) cation. The subsequent reversible one- and two-electron processes arise from the ligand framework and pendant ferrocenes, respectively. PMID- 22775511 TI - ZNF804A rs1344706 variant and schizophrenia in a Romanian population from Cluj Napoca. AB - The ZNF804A rs1344706 variant was the first risk factor to be identified through genome-wide association studies and follow-up studies with meta-analysis for schizophrenia as well as bipolar disorders; we investigated 231 schizophrenia and 222 controls to see whether this particular variant was associated with schizophrenia in a Romanian population from Cluj Napoca. Clearly, there was no association between the ZNF804A rs1344706 variant and schizophrenia. Our study provides evidence for those that found no association with schizophrenia. A surprising result of our study was that the T allele frequency is the highest, thus far among the ethnic groups studied. We used a PCR-RFLP method that had been recently developed in our laboratory to the genotype ZNF804A rs1344706 variant. In conclusion, the ZNF804A rs1344706 variant was not associated with schizophrenia in the Romanian population from Cluj Napoca (chi(2)=0.734, p=0.693). PMID- 22775512 TI - Nuclear dynamics of histone H3 trimethylated on lysine 9 and/or phosphorylated on serine 10 in mouse cloned embryos as new markers of reprogramming? AB - Somatic cell nuclear transfer (SCNT) is the injection of a donor nucleus into an enucleated egg. Despite the use of this technology for many years in research, it is still quite inefficient. One of the causes for this is thought to be incorrect or incomplete genome reprogramming. Embryos produced by nuclear transfer (cloned embryos) very often present abnormal epigenetic signatures and irregular chromatin reorganization. Of these two issues, the issue of chromatin rearrangements within the nuclei after transfer is the least studied. It is known that cloned embryos often present pericentromeric heterochromatin clumps very similar to the chromocenters structures present in the donor nuclei. Therefore, it is believed that the somatic nuclear configuration of donor nuclei, especially that of the chromocenters, is not completely lost after nuclear transfer, in other words, not well reprogrammed. To further investigate pericentromeric heterochromatin reorganization after nuclear transfer, we decided to study its rearrangements in cumulus-derived clones using several related epigenetic markers such as H3S10P, H3K9me3, and the double marker H3K9me3S10P. We observed that two of these markers, H3S10P and H3K9me3S10P, are the ones found on the part of the pericentromeric heterochromatin that is remodeled correctly, resembling exactly the embryonic heterochromatin configuration of naturally fertilized embryos. Conversely, H3K9me3 and heterochromatin protein 1 beta (HP1beta)-associated protein were also detected in the perinuclear clumps of heterochromatin, making obvious the maintenance of the somatic epigenetic signature within these nuclear regions. Our results demonstrate that H3S10P and H3K9me3S10P could be good candidates for evaluating heterochromatin reorganization following nuclear reprogramming. PMID- 22775513 TI - Patterns of subsequent malignancies after Hodgkin lymphoma in children and adults. AB - To evaluate the impact of reduced radiation and combined modality therapy (CMT) in the treatment of Hodgkin lymphoma, we assessed the risk of second malignant neoplasms (SMNs) in patients who received extended-field radiotherapy only and patients who underwent CMT. Among 404 patients treated at Yale during 1970-2004, the risk of solid SMNs was elevated in the radiotherapy only group (n = 198, median follow-up = 21.1 years) compared to the general population, with a standardized incidence ratio (SIR) of 1.85 [95% confidence interval (CI): 1.17 2.78]. No increase was observed in the CMT group (n = 206, median follow-up = 14.3 years), although potential differences in SMN risk were indicated across the age spectrum in subgroup analysis. Patients who received mustard-containing regimens had increased risks for haematological SMNs (SIR = 8.74) and all SMNs (SIR = 1.85). When the analysis was stratified by age at diagnosis, children (0 20 years) had a significantly higher risk of SMNs (SIR = 5.24, 95% CI: 2.26 10.33), regardless of the treatment received. These findings suggest that recent treatment options utilizing lower dose radiation and less intense alkylator chemotherapy might be associated with lower incidences of SMNs among adults but not necessarily children. PMID- 22775514 TI - Open access musings. PMID- 22775516 TI - What is keeping us busy in the Pharmacy? PMID- 22775517 TI - Home medicines reviews: a quantitative study of the views of recipients and eligible non-recipients. AB - OBJECTIVE: There is a lack of knowledge regarding recipients' experiences with, perceptions of, and willingness to reuse the Home Medicines Review (HMR) programme in Australia. In addition, little is known about eligible non recipients' awareness of and willingness to use the HMR service. The aim of the study was therefore to explore perceptions of, and willingness to use, HMRs. METHODS: A cross-sectional questionnaire was conducted with recipients and eligible non-recipients of HMRs. Eligible non-recipients were defined as those who had not had an HMR and were at risk of medication misadventure. The questionnaire was distributed by 264 practising pharmacists throughout Australia. RESULTS: A total of 595 out of 1893 (31%) HMR recipients and 293 out of 1829 (16%) eligible non-recipients completed the questionnaires. Overall, 91% of recipients were satisfied with the service. Compared with eligible non recipients, recipients were more willing to have an HMR if their general practitioner (GP) suggested it (91% versus 71%, P < 0.001) and more willing to ask for an HMR if they were having concerns about their medicines (82% versus 63%, P < 0.001). Among eligible non-recipients, 23% were aware of HMRs. Predominantly pharmacists (68%) and GPs (36%) provided awareness of HMRs, which was associated with increased willingness to have an HMR if their GP suggested it (83% versus 67%, P < 0.014). CONCLUSIONS: An overwhelming majority of patients were satisfied with the HMR programme. Experience with HMR, and to a lesser extent, prior awareness, increased willingness to use HMR. Therefore, pharmacists and GPs who introduce HMR to eligible non-recipients may increase their willingness to use this service. PMID- 22775518 TI - Community pharmacy services in the United Arab Emirates. AB - OBJECTIVES: To identify the type and frequency of services provided through community pharmacies in the United Arab Emirates (UAE). METHODS: A survey was conducted using an anonymous questionnaire distributed by hand to 700 community pharmacies. Items included information about the pharmacists and pharmacies, type of products sold, type and extent of enhanced services provided and perceived barriers to providing these services. KEY FINDINGS: Most pharmacies provided a wide range of medicinal and non-medicinal products. The frequency with which services were provided was assessed on a scale of 1 (never) to 5 (always). Enhanced professional services were not provided to a large extent in most pharmacies. Fewer than one-third (29%) reported they always supplied printed information to patients (mean = 3.37, 95% confidence interval = 3.23-3.52); fewer than one-third (28%) counselled patients on a regular basis (3.25, 3.09-3.40); nearly two-thirds (62%) reported monitoring patients' adherence to therapy at least sometimes (2.96, 2.81-3.10). Most pharmacies (92%) in the UAE did not routinely keep patient records (2.09, 1.96-2.32). While just over a quarter of respondents claimed that they always reported medication errors (27%) and adverse drug reactions (28%), these activities were not often performed in around 40% of pharmacies. CONCLUSIONS: This is the first study to explore the type and extent of professional services provided through community pharmacies in the UAE and provides baseline data critical to inform the development of strategies to improve the quality of community pharmacy services. PMID- 22775519 TI - Patient-specific factors relating to medication adherence in a post-percutaneous coronary intervention cohort. AB - OBJECTIVE: To explore the association between medication adherence and qualitatively characterised patient-specific themes relating to medication adherence in patients following percutaneous coronary intervention (PCI). METHODS: Data-collection questionnaires and qualitative topic guides were piloted in two patients. A validated questionnaire generated an adherence score for a convenience sample of 20 patients within 7 days of PCI. Semi-structured qualitative interviews were subsequently carried out with all patients to explore patient-specific themes relating to measured medication adherence. KEY FINDINGS: Fourteen out of 20 patients (70%) had scores indicative of good adherence. Key factors associated with good adherence included having a good relationship with the doctor, having an understanding of the condition, knowledge of the indications and consequences of non-adherence, perceived health benefits and medications eliciting tangible symptom control. There were misconceptions of concern regarding adverse drug reactions and the importance of aspirin, both of which had a negative effect on adherence. The role of the community pharmacist was sometimes, although not always, misunderstood. CONCLUSION: This study suggests there is an association between patients' beliefs, knowledge, understanding and misconceptions about medication and their adherence in a post PCI cohort. To optimise medication adherence it is vital for prescribers to remain patient-focused and cognisant of patient-specific themes relating to medication adherence. PMID- 22775520 TI - A clinical knowledge measurement tool to assess the ability of community pharmacists to detect drug-related problems. AB - INTRODUCTION: Drug-related problems (DRPs) are associated with significant morbidity and mortality, with most DRPs thought to be preventable. Community pharmacists can detect and either prevent or resolve many of these DRPs. A survey based clinical knowledge measurement tool was designed and validated to estimate a community pharmacist's clinical knowledge and ability to detect and appropriately resolve DRPs. METHODS: Nine clinical cases with seven multiple choice statements (63 statements in total) were constructed, based on scenarios that were found to occur frequently in Australian community pharmacies. The statements aimed to assess a pharmacist's ability to identify, gather relevant information about and make appropriate recommendations to resolve, a DRP. The survey was pilot tested with 18 academics at three Australian pharmacy schools, resulting in the removal of 23 statements. The survey was then administered to undergraduate pharmacy students (28 fourth-year, 41 third-year and 42 first-year students) and to 433 Australian community pharmacists who were participating in an intervention documentation trial. The pharmacists' resultant survey scores were correlated against their actual rate of documenting clinical interventions. RESULTS: The tool had relatively good internal consistency. Significant differences were seen between the three groups of students (P < 0.01). Community pharmacists with additional clinical qualifications had a significantly higher score than other participating pharmacists (P < 0.01). A moderate, but significant, correlation was seen between the pharmacists' survey score and their clinical intervention rate in practice during the trial (P < 0.01). CONCLUSION: The clinical knowledge measurement tool appeared to estimate a pharmacist's ability to detect and resolve DRPs within the community pharmacy environment. PMID- 22775521 TI - Exploring stakeholder perspectives on medication review services for older residents in retirement villages. AB - OBJECTIVE: To explore stakeholder perspectives on a government-subsidised Home Medicines Review (HMR) service and factors affecting the uptake of HMRs for older residents of retirement villages in Australia. METHODS: Thirty-two in-depth interviews and four focus groups were undertaken with a purposive sample of 32 residents of retirement villages, 10 pharmacists, nine general practitioners (GPs) and a general practice nurse. Data were transcribed verbatim and analysed using the framework approach. KEY FINDINGS: Three major themes were identified: participants' perceptions of the HMR service, barriers to the uptake of HMRs and strategies for increasing the uptake of HMR. Residents had positive, negative or mixed perceptions, whereas health professionals were generally positive about the benefits of the service. Barriers to the uptake of HMRs were related to GPs, pharmacists, patients and the healthcare system. A strategy recommended by multiple stakeholders for increasing the uptake of HMRs was to use a multi faceted intervention targeting residents and their health professionals. CONCLUSIONS: Multiple barriers to the uptake of HMRs and multiple strategies for increasing the uptake of HMRs were identified. These findings could inform the design of interventions to improve uptake of HMRs by residents and health professionals, in turn leading to better medicine use and safety. PMID- 22775522 TI - Workload and its impact on community pharmacists' job satisfaction and stress: a review of the literature. AB - OBJECTIVE: The objective was to identify, review and evaluate published literature on workloads of pharmacists in community pharmacy. It included identification of research involving the measurement of pharmacist workload and its impact on stress levels and job satisfaction. The review focused on literature relating to practice in the UK. METHODS: Electronic databases were searched from 1995 to May 2011. In addition, manual searches were completed for documents not available electronically. The findings were analysed with specific focus on research methodology, workload and its impact on pharmacist job satisfaction and stress levels. KEY FINDINGS: Thirteen relevant studies relating to workload in community pharmacy alone or in conjunction with job satisfaction and stress were identified. One utilised both qualitative and quantitative methods to identify differences in pharmacist workload in retail pharmacy businesses before and after the implementation of the 2005 English and Welsh community pharmacy contractual framework. This indicated that pharmacists spend most of their working day dispensing. The majority of studies suggested community pharmacists generally perceived that workload levels were increasing. Several also stated that increased workload contributed to increasing job-related stress and decreasing job satisfaction. No studies reporting dispensing rates for community pharmacies in the UK were identified and there was limited evidence concerning time devoted to non-dispensing services. One study investigated the differences between self-estimated and actual workload. CONCLUSIONS: Whilst there is a clear perception that the type and amount of work output expected from individual community pharmacists has been changing and increasing over the last few decades, pharmacists are viewed as continuing to remain based in the dispensary. The impact of such changes to the practice of community pharmacy in the UK is poorly defined, although links have been made to increasing levels of pharmacist job dissatisfaction and stress. PMID- 22775523 TI - Does the clinical clerkship course improve students' attitudes towards pharmaceutical care? AB - OBJECTIVE: The clinical clerkship course undertaken by final year pharmacy students to improve their pharmacotherapeutic knowledge and professional competence was tested in this study to see its effect on students' attitudes towards pharmaceutical care. METHODS: A 13-item Pharmaceutical Care Attitude Survey (PCAS) questionnaire was administered to final year pharmacy students at the University of Nigeria, before and after the 8-week-long clinical clerkship course. Statistical analyses were conducted on retrieved data. RESULTS: One hundred and five students (95% of the sample) completed the pre-clerkship phase and 97 students (92% of pre-clerkship students) completed the post-clerkship phase. Of the 13 items, three increased significantly (P < 0.05)--that is, improved--and there were indications that a further six improved, with two having no change and two items getting worse after the clerkship course. CONCLUSION: This study showed that the clerkship course improved students' attitudes towards areas concerning professional duty but not those relating to benefit and responsibility. The importance of professional benefit needs to be emphasized by preceptors. PMID- 22775525 TI - Langmuir. Biographical sketches. PMID- 22775524 TI - Clinical development of IMOJEV (r)--a recombinant Japanese encephalitis chimeric vaccine (JE-CV). AB - INTRODUCTION: Japanese encephalitis (JE) is a disease of the central nervous system (CNS) caused by Japanese encephalitis virus (JEV). JE is endemic in most of the South-East Asian countries and in some parts of the Western Pacific. As mosquito control is ineffective, currently vaccination is the only available control measure. A mouse brain-derived inactivated JE vaccine (MBDV) has been in use for a long time; however, it is not feasible for mass vaccination due to the ethical and safety issues. With the World Health Organization (WHO) appealing for the development of novel, safe and affordable JE vaccines, several vaccine candidates have been developed in the recent times and IMOJEV (r) is one among them. AREAS COVERED: This review presents a brief account of various developmental, immunological and ethical issues related to IMOJEV(r) and provides an in-depth account of its clinical development and efficacy in comparison to other JE vaccines. EXPERT OPINION: IMOJEV(r) is a safe and efficacious vaccine. If made affordable through financial assistance from health agencies or by its production in set ups where operational costs are lower, it may become an ideal vaccine for mass vaccination in JE endemic regions. PMID- 22775526 TI - Factors contributing to false-negative and potential false-negative cytology reports in SurePathTM liquid-based cervical cytology. AB - OBJECTIVES: The characteristics of false-negative conventional cervical cytology smears have been well documented, but there is limited literature available for liquid-based cytology (LBC), especially SurePathTM samples. We aimed to assess the characteristics of false-negative SurePath LBC samples. METHODS: Over a period of 5 years, an audit of false-negative reports in SurePath cervical cytology was undertaken. In a workload of 183, 112 samples, 481 (0.3%) false negatives were identified using two routes: those detected by routine laboratory internal quality control (rapid pre-screening) (n = 463) and those reported as normal (true false negatives) with concurrent high-grade cervical histology (n = 18). Ninety-five false-negative cases with a subsequent biopsy reported as at least cervical intraepithelial neoplasia grade 2 (CIN2+) were reviewed for a number of different cytomorphological features. RESULTS: Of 95 samples with subsequent CIN2+, 30.5% predominately contained microbiopsies/hyperchromatic crowded cell groups (HCGs), 27.3% sparse dyskarytotic cells, 4.2% pale cell dyskaryosis, 6.3% small dyskaryotic cells; 3.2% were misinterpreted cells, 8.4% contained other distracting cells, 7.4% were low contrast, 5.3% were unexplained and 7.4% were true negatives. The mean number of microbiopsies/HCGs in that category was 4.6. The mean number of abnormal cells in the sparse dyskaryotic cell category was 13.8. CONCLUSIONS: Microbiopsies/HCGs were the commonest reason for false negatives. They were usually present in sufficient numbers to be detected but interpretation could be problematic. Dispersed single abnormal cells were usually not identified because of their scarcity or the presence of distracters. PMID- 22775527 TI - Assessment of marginal adaptation after apicoectomy and apical sealing with Nd:YAG laser. AB - OBJECTIVE: Recurrent periapical disease poses a substantial challenge to the dental practitioner. However, the use of novel methods and materials in periapical surgery has increased the success rates of treatment. The objective of this study was to assess the effects of mineral trioxide aggregate (MTA) retrofilling and apical sealing with Nd:YAG laser (at 10 Hz, 150 mJ, 1.5 W, in 60 sec pulses) as adjuncts to apicoectomy. METHODS: Perpendicular root end resection was performed with diamond-coated burs on 40 canine teeth previously subjected to endodontic treatment. Teeth were randomly allocated into four groups: group A, apicoectomy alone; group B, apicoectomy+Nd:YAG laser; group C, apicoectomy+MTA retrofilling; group D, apicoectomy+MTA retrofilling+Nd:YAG laser. Specimens were embedded in epoxy resin and sliced lengthwise and crosswise. RESULTS: Scanning electron microscopy (SEM) analysis showed more homogeneous and canaliculi-free apical surfaces in groups B and D (p<0.01). Marginal gaps between the dentin surface and filling material were observed in decreasing order of gap size in groups B, A, D, and C (p<0.01) for cross-sectional analysis. Energy-dispersive X ray spectrometry (EDS) revealed greater phosphorus (p<0.01) and lower calcium (p<0.01) ion content in the Nd:YAG-irradiated groups. CONCLUSIONS: In this study, Nd:YAG laser irradiation had a positive effect on dentin surface sealing, despite an untoward dimensional effect when associated with MTA retrofilling. PMID- 22775528 TI - Camouflage through an active choice of a resting spot and body orientation in moths. AB - Cryptic colour patterns in prey are classical examples of adaptations to avoid predation, but we still know little about behaviours that reinforce the match between animal body and the background. For example, moths avoid predators by matching their colour patterns with the background. Active choice of a species specific body orientation has been suggested as an important function of body positioning behaviour performed by moths after landing on the bark. However, the contribution of this behaviour to moths' crypticity has not been directly measured. From observations of geometrid moths, Hypomecis roboraria and Jankowskia fuscaria, we determined that the positioning behaviour, which consists of walking and turning the body while repeatedly lifting and lowering the wings, resulted in new resting spots and body orientations in J. fuscaria and in new resting spots in H. roboraria. The body positioning behaviour of the two species significantly decreased the probability of visual detection by humans, who viewed photographs of the moths taken before and after the positioning behaviour. This implies that body positioning significantly increases the camouflage effect provided by moth's cryptic colour pattern regardless of whether the behaviour involves a new body orientation or not. Our study demonstrates that the evolution of morphological adaptations, such as colour pattern of moths, cannot be fully understood without taking into account a behavioural phenotype that coevolved with the morphology for increasing the adaptive value of the morphological trait. PMID- 22775529 TI - Characterization and immunosuppressive properties of mesenchymal stem cells from periapical lesions. AB - AIM: Mesenchymal stem cells (MSCs) isolated from healthy dental tissues are being investigated as an alternative source of MSCs for the treatment of damaged tissues and inflammatory diseases. Here we investigated whether MSCs from periapical lesions (PL-MSCs) also possess multi-lineage differentiation capacity and immunomodulatory properties. MATERIAL & METHODS: PL-MSCs, isolated by collagenase/DNAse digestion from surgically extracted PLs, were compared with MSCs from non-inflamed dental pulp (DP-MSCs) and dental follicle (DF-MSCs) for their phenotype and multi-potent differentiation potential. The anti-inflammatory and immunomodulatory effects of PL-MSCs were studied in co-culture with peripheral blood mononuclear cells (PB-MNCs) and PL-inflammatory cells (PL-ICs). RESULTS: PL-MSCs were characterized by typical MSCs phenotype, lower clonogenicity and self-renewal rate, compared to DF-MSCs and DP-MSCs. These cells possess the potential to differentiate into adipocyte-, osteoblast- and chondrocyte-like cells in vitro, which differs from that of DP-MSCs and DF-MSCs. PL-MSCs inhibited phytohemaglutinine-induced proliferation of PB-MNCs and production of IL-2, IFNgamma and IL-5 in the co-culture, probably via TGF-beta dependent mechanisms. These cells also suppressed the production of IL-1beta, IL 6, and TNF-alpha by PL-ICs via soluble mediators, whereas the suppression of IL-8 production required a direct cell-to-cell contact. CONCLUSION: The differentiation potential of PL-MSCs and their immunosuppressive/anti inflammatory properties could be beneficial for the treatment of chronic periodontal diseases. PMID- 22775531 TI - Cure neurodevelopmental genetic disorders, please. PMID- 22775530 TI - Postischemic brain infiltration of leukocyte subpopulations differs among murine permanent and transient focal cerebral ischemia models. AB - Cellular and humoral inflammations play important roles in ischemic brain injury. The effectiveness of immunomodulatory therapies may critically depend on the chosen experimental model. Our purpose was to compare the post-ischemic neuroinflammation among murine permanent and transient middle cerebral artery occlusion (MCAO) models. Permanent MCAO was induced by transtemporal electrocoagulation and 30 minutes or 90 minutes transient MCAO was induced by intraluminal filament in C57BL/6 mice. Infiltration of leukocyte subpopulations was quantified by immunohistochemistry and fluorescence-activated cell sorting. Cerebral cytokine and adhesion molecule expression was measured by real-time polymerase chain reaction (RT-PCR). Neutrophil infiltration was noted at 24 h after transient MCAO, but did not further increase until 5 days in the permanent MCAO model. Few T cells were observed in both MCAO models at 24 h, but permanent MCAO demonstrated much more infiltrating T cells at 5 days. Pronounced microglial activation was evident at 24 h and 5 days after permanent but not after transient MCAO. The number of invading NK cells and expression of MHCII on CD11b+ cells did not differ among the three groups. Five days after MCAO, the expression of IL-1, TNF-alpha and IFN-gamma and of the adhesion molecules ICAM-1 and VCAM-1 was significantly higher in the permanent than in the transient MCAO groups. Cellular and humoral inflammation differs substantially among commonly used MCAO models. Neuroinflammation is more pronounced after permanent electrocoagulatory MCAO compared with 30 minutes and 90 minutes filament-MCAO. PMID- 22775532 TI - The AmpliChip(r) CYP450 test and response to treatment in schizophrenia and obsessive compulsive disorder: a pilot study and focus on cases with abnormal CYP2D6 drug metabolism. AB - AIM: Genetic factors can result in variance in drug metabolism enzyme function, which is one major mechanism impacting on interindividual variability in response and side effects. We therefore performed a pilot study to investigate genetic variants in the drug metabolizing enzymes CYP2D6 and CYP2C19. METHODS: We evaluated 35 schizophrenic and 39 obsessive compulsive disorder (OCD) patients treated with various antipsychotics and antidepressants. Patients were assessed for treatment response and side effects. Genotyping for CYP2D6 and CYP2C19 was performed using the AmpliChip((r)). Statistical analysis was performed using analysis of variance and Fisher's exact test. Cases of poor metabolizers (PMs) or ultrarapid metabolizers (UMs) were examined in further detail to assess medication outcomes. RESULTS: Statistical analysis identified no overall significant association of CYP2D6 metabolizer status with treatment response or occurrence of side effects. Nonetheless, case reports of PM and UM individuals indicated lack of response and/or occurrence of side effects in most of these patients. A secondary analysis comparing OCD subjects with impaired 2D6 function to extensive metabolizers was significant (p=0.021). CONCLUSION: Although not conclusive, there was some association between CYP2D6 impaired metabolic status and medication response. Our case reports suggest a potential clinical benefit of CYP genotyping for specific patients. Further validation of CYP2D6 and CYP2C19 testing in prospective, randomized trials is warranted. PMID- 22775533 TI - Influence of solvent on polymer prequaternization toward anion-conductive membrane fabrication for all-vanadium flow battery. AB - Triethylamine- (TEA-) enabled prequaternization of a polymer for nonalkaline anion-exchange membrane (AEM) fabrication is more facile and environmentally benign than the conventional trimethylamine-based postquaternization route. It is also more compatible with forming a microphase-separated membrane morphology that can facilitate ion transport. However, most studies of TEA-quaternized AEMs have reported unsatisfactory conductivities, and no examples of their application in all-vanadium flow batteries (VFBs) have been reported. In this work, we aim to address this issue and demonstrate that, by employing a favorable solvent, polysulfone can be prequaternized to a high level with TEA and further fabricated into an AEM showing good conductivity (18.2 mS cm(-1) at room temperature) and impressive VFB performance (Coulombic efficiency above 98% and energy efficiency above 80% at 80 mA cm(-2)). In contrast, when an unfavorable solvent is used, membrane quaternization does not occur significantly. This contrast is shown to result from the absence or presence of solvent-TEA competition during quaternization, which is related to the the electron-donating or -withdrawing properties of the solvents used. Our study adds new understanding to the quaternization chemistry of AEMs and also represents the first example, to our knowledge, of a TEA-quaternized AEM yielding high VFB efficiencies. PMID- 22775535 TI - Can zinc really exist in its oxidation state +III? AB - Very recently, a thermochemically stable Zn(III) complex has been predicted by Samanta and Jena (J. Am. Chem. Soc. 2012, 134, 8400-8403). In contrast to their conclusions we show here by quantum chemical calculations that (a) Zn(AuF(6))(3) is not a thermochemically feasible compound, and (b) even if it could be made, it would not represent a Zn(III) oxidation state by any valid definition. PMID- 22775534 TI - Patients' willingness to accept the risks and benefits of new treatments for chronic hepatitis C virus infection. AB - BACKGROUND: Some patients with chronic hepatitis C virus (HCV) infection forego treatment due to concerns about treatment efficacy, treatment duration, and side effects. OBJECTIVE: The purpose of this study was to quantify patient preferences among possible outcomes associated with new, direct-acting antiviral agents (DAAs) for the treatment of HCV infection and determine which treatment features are most important to patients in making treatment decisions. METHODS: Adult participants with a self-reported physician diagnosis of HCV infection in five countries completed a web-enabled, choice-format conjoint analysis survey. The survey presented participants with 20 treatment-choice questions. Each treatment choice question included a pair of hypothetical treatment profiles with varying levels of six attributes: treatment duration; chance of getting rid of the virus completely (i.e. likelihood of a sustained virologic response [SVR]); weeks on an additional, third medicine (i.e. a DAA); risk of a severe rash; risk of severe anemia; and number of times a day the third medicine is taken. Treatment-choice questions were based on a pre-determined experimental design with known statistical properties. Random-parameters logit was used to estimate preference weights for all attribute levels and the mean relative importance of each attribute. RESULTS: 284 participants completed the survey. Likelihood of an SVR was the most important outcome to participants, followed by severe anemia risk, severe rash risk, therapy type (a combination of total weeks of treatment and weeks on the third medicine), and dosing of the third medicine. Controlling for other factors, preferences were similar across all therapy types examined. CONCLUSION: Patients with HCV infection indicate a willingness to accept an increased risk of side effects for sufficient improvement in the likelihood of treatment response. PMID- 22775536 TI - Identification of a haem domain in human soluble adenylate cyclase. AB - The second messengers cAMP and cGMP mediate a multitude of physiological processes. In mammals, these cyclic nucleotides are formed by related Class III nucleotidyl cyclases, and both ACs (adenylate cyclases) and GCs (guanylate cyclases) comprise transmembrane receptors as well as soluble isoforms. Whereas sGC (soluble GC) has a well-characterized regulatory HD (haem domain) that acts as a receptor for the activator NO (nitric oxide), very little is known about the regulatory domains of the ubiquitous signalling enzyme sAC (soluble AC). In the present study, we identify a unique type of HD as a regulatory domain in sAC. The sAC-HD (sAC haem domain) forms a larger oligomer and binds, non-covalently, one haem cofactor per monomer. Spectral analyses and mutagenesis reveal a 6-fold co ordinated haem iron atom, probably with non-typical axial ligands, which can bind both NO and CO (carbon monoxide). Splice variants of sAC comprising this domain are expressed in testis and skeletal muscle, and the HD displays an activating effect on the sAC catalytic core. Our results reveal a novel mechanism for regulation of cAMP signalling and suggest a need for reanalysis of previous studies on mechanisms of haem ligand effects on cyclic nucleotide signalling, particularly in testis and skeletal muscle. PMID- 22775538 TI - Technetium tetrachloride revisited: a precursor to lower-valent binary technetium chlorides. AB - Technetium tetrachloride has been prepared from the reaction of technetium metal with excess chlorine in sealed Pyrex ampules at elevated temperatures. The product was characterized by single-crystal and powder X-ray diffraction, transmission electron microscopy, scanning electron microscopy, and alternating current magnetic susceptibility. Solid TcCl(4) behaves as a simple paramagnet from room temperature down to 50 K with MU(eff) = 3.76 MU(B). Below 25 K, TcCl(4) exhibits an antiferromagnetic transition with a Neel temperature (T(N)) of ~24 K. The thermal behavior of TcCl(4) was investigated under vacuum at 450 degrees C; the compound decomposes stepwise to alpha-TcCl(3) and TcCl(2). PMID- 22775537 TI - Nucleostemin in injury-induced liver regeneration. AB - The high regenerative capacity of liver contributes to the maintenance of its size and function when injury occurs. Partial hepatectomy induces division of mature hepatocytes to maintain liver function, whereas severe injury stimulates expansion of undifferentiated hepatic precursor cells, which supply mature cells. Although several factors reportedly function in liver regeneration, the precise mechanisms underlying regeneration remain unclear. In this study, we analyzed expression of nucleostemin (NS) during development and in injured liver by using transgenic green fluorescent protein reporter (NS-GFP Tg) mice. In neonatal liver, the hepatic precursor cells that give rise to mature hepatocytes were enriched in a cell population expressing high levels of NS. In adult liver, NS was abundantly expressed in mature hepatocytes and rapidly upregulated by partial hepatectomy. Severe liver injury promoted by a diet containing 3,5 diethoxycarbonyl-1,4-dihydrocollidine induced the emergence of NS-expressing ductal epithelial cells as hepatic precursor cells. NS knockdown inhibited both hepatic colony formation in vitro and proliferation of hepatocytes in vivo. These data strongly suggest that NS plays a critical role in regeneration of both hepatic precursor cells and hepatocytes in response to liver injury. PMID- 22775539 TI - Pterygium after hyperopic laser-assisted sub-epithelial keratomileusis (LASEK). AB - A 61-year-old Caucasian woman with hyperopia presented for laser refractive surgery. She had healthy eyes with the exception of a less than 0.5 mm Salzmann's nodule at 5 o'clock near the limbus of the right eye. She underwent bilateral hyperopic laser-assisted sub-epithelial keratomileusis (LASEK) combined with removal of the Salzmann's nodule. At six months, she was emmetropic with unaided vision of 6/6; however, at 10 months, she noticed a reduction of acuity in her right eye and was found to have a pterygium at 5 o'clock, encroaching 3.5 mm onto the corneal surface. She underwent excision biopsy, local application of mitomycin-C (0.2 mg/ml for two minutes) and conjunctival auto-grafting. Following surgery for the pterygium, vision returned to 6/6 unaided but six months later, there was limited recurrence (1.5 mm) of the pterygium reducing unaided vision to 6/9, due to the induction of astigmatism of -1.25 dioptres. This has remained stable for 14 months. Pterygium growth may be associated with surface excimer laser surgery and the presence of peripheral Salzmann's nodules might be a risk factor. PMID- 22775540 TI - Photodegradable iron(III) cross-linked alginate gels. AB - Biocompatible photoresponsive materials are of interest for targeted drug delivery, tissue engineering, 2D and 3D protein patterning, and other biomedical applications. We prepared light degradable hydrogels using a natural alginate polysaccharide cross-linked with iron(III) cations. The "hard" iron(III) cations used to cross-link the alginate hydrogel were found to undergo facile photoreduction to "soft" iron(II) cations in the presence of millimolar concentrations of sodium lactate. The "soft" iron(II) cations have a decreased ability to cross-link the alginate which results in dissolution of the hydrogel and the formation of a homogeneous solution. The photodegradation is done using long wave UV or visible light at neutral pH. The very mild conditions required for the photodegradation and the high rate at which it occurs suggest applications for iron(III) cross-linked alginate hydrogels as light-controlled biocompatible scaffolds. PMID- 22775541 TI - Photoreduction of SERS-active metallic nanostructures on chemically patterned ferroelectric crystals. AB - Photodeposition of metallic nanostructures onto ferroelectric surfaces is typically based on patterning local surface reactivity via electric field poling. Here, we demonstrate metal deposition onto substrates which have been chemically patterned via proton exchange (i.e., without polarization reversal). The chemical patterning provides the ability to tailor the electrostatic fields near the surface of lithium niobate crystals, and these engineered fields are used to fabricate metallic nanostructures. The effect of the proton exchange process on the piezoelectric and electrostatic properties of the surface is characterized using voltage-modulated atomic force microscopy techniques, which, combined with modeling of the electric fields at the surface of the crystal, reveal that the deposition occurs preferentially along the boundary between ferroelectric and proton-exchanged regions. The metallic nanostructures have been further functionalized with a target probe molecule, 4-aminothiophenol, from which surface-enhanced Raman scattering (SERS) signal is detected, demonstrating the suitability of chemically patterned ferroelectrics as SERS-active templates. PMID- 22775542 TI - Cell counts and survival to vitrification of bovine in vitro produced blastocysts subjected to sublethal high hydrostatic pressure. AB - This work analyses the effects of a high hydrostatic pressure (HHP) treatment on in vitro survival of in vitro produced (IVP) bovine embryos vitrified with the Cryologic Vitrification Method (CVM). Consequences on embryo quality in terms of cell proliferation and differentiation, and levels of embryonic Heat Shock Protein 70 (Hsp-70) were also examined. Day 7 and 8 bovine in vitro-produced blastocysts were submitted to an HHP treatment (60 MPa, at 32 degrees C for 1 h) and allowed to recover for 1 or 2 h in culture medium. The HHP treatment did not improve blastocyst survival rates after vitrification/warming. Survival (24 h post-warming) and hatching (48 h post-warming) rates were 79.3 +/- 4.9 and 51.8 +/- 4.2 vs 73.9 +/- 4.2 and 44.7 +/- 4.1 for untreated controls and HHP-treated embryos, respectively. Total cell numbers measured in fresh embryos were reduced after 1 h at 32 degrees C, with or without HHP treatment, indicating that cell proliferation was stopped as a result of stress. Vitrified HHP-treated embryos that hatched at 48 h after warming showed increased cell numbers in their ICM compared with untreated controls (50.2 +/- 3.1 vs 38.8 +/- 2.7), indicating higher embryo quality. Treatment of blastocysts with HHP did not alter the level of the Hsp-70 protein. In our conditions, HHP treatment did not affect the cryoresistance of these embryos. However, combination of HHP treatment and vitrification in fibreplugs resulted in an increase in the ICM cell number of hatched embryos 48 h post-warming. PMID- 22775543 TI - Allergic nickel dermatitis caused by playing the guitar: case report and assessment of nickel release from guitar strings. PMID- 22775544 TI - Dipyridamole-induced eczematous drug eruption with positive patch test reaction. PMID- 22775545 TI - Allergic contact dermatitis caused by polyester-8 (Polycrylene(r)) in a sunscreen moisturizer. PMID- 22775546 TI - Airborne allergic contact dermatitis in a parquet fitter. PMID- 22775547 TI - Variability in patch test reactivity over time, falsely indicating patch test sensitization, in a patient tested with palladium salts. PMID- 22775548 TI - Occupational irritant contact dermatitis caused by Lobelia richardii in an Ethiopian flower farm. PMID- 22775549 TI - Contact sensitization to dittany of Crete (Origanum dictamnus) in a herbal remedy. PMID- 22775550 TI - Occupational contact allergy to a Phalaenopsis orchid cultivar. PMID- 22775551 TI - Measuring and modelling body mass index among a cohort of urban children living with disadvantage. AB - AIM: To report on baseline outcomes of body mass index, eating habits and physical activity of a cohort of urban disadvantaged children from a longitudinal evaluation of a school based, health promoting initiative. BACKGROUND: The healthy schools programme was developed for implementation in schools located in disadvantaged areas of Dublin, Ireland. DESIGN: A prospective, cohort study design was implemented. METHOD: A 3-year longitudinal evaluation was conducted in five intervention and two comparison schools between 2009-2011. Data were collected on each participating child to determine their eating habits, levels of physical activity and body mass index at year 1 (baseline), year 2 and year 3. Independent t-tests were used to compare mean values, chi-square and Fishers exact tests were used to compare proportions at baseline. RESULTS: Participation rates were over 50%. Older children reported eating on average more fruit and vegetables than younger children; breakfast was often eaten on the way to, or in school and in one age group 16.7% of intervention children reported they did not eat breakfast that day. Levels of physical activity varied with over 70% of younger children stating they never played a sport. In intervention schools over one quarter of all children were either overweight or obese. A comparison was conducted between the proportion of 9-year olds overweight and obese in our disadvantaged cohort and a national random sample of 8500 9-year olds and no important differences were observed. CONCLUSION: Baseline results indicate that body mass index rates particularly among pre adolescent, urban disadvantaged girls are of concern. PMID- 22775552 TI - Effect of increased pCO(2) on bacterial assemblage shifts in response to glucose addition in Fram Strait seawater mesocosms. AB - Ocean acidification may stimulate primary production through increased availability of inorganic carbon in the photic zone, which may in turn change the biogenic flux of dissolved organic carbon (DOC) and the growth potential of heterotrophic bacteria. To investigate the effects of ocean acidification on marine bacterial assemblages, a two-by-three factorial mescosom experiment was conducted using surface sea water from the East Greenland Current in Fram Strait. Pyrosequencing of the V1-V2 region of bacterial 16S ribosomal RNA genes was used to investigate differences in the endpoint (Day 9) composition of bacterial assemblages in mineral nutrient-replete mesocosms amended with glucose (0 MUM, 5.3 MUM and 15.9 MUM) under ambient (250 MUatm) or acidified (400 MUatm) partial pressures of CO(2) (pCO(2)). All mesocosms showed low richness and diversity by Chao1 estimator and Shannon index, respectively, with general dominance by Gammaproteobacteria and Flavobacteria. Nonmetric multidimensional scaling analysis and two-way analysis of variance of the Jaccard dissimilarity matrix (97% similarity cut-off) demonstrated that the significant community shift between 0 MUM and 15.9 MUM glucose addition at 250 MUatm pCO(2) was eliminated at 400 MUatm pCO(2). These results suggest that the response potential of marine bacteria to DOC input may be altered under acidified conditions. PMID- 22775553 TI - Intermittent preventive treatment of malaria in pregnant women and infants: making best use of the available evidence. AB - INTRODUCTION: Malaria continues to represent a huge global health burden on the most vulnerable populations. The Intermittent Preventive Treatment (IPT) strategy has been shown to be an efficacious intervention in preventing most of the deleterious effects of malaria in pregnant women and infants. Yet, the effectiveness of the IPT strategy may be impaired by the increasing resistance to sulfadoxine-pyrimethamine (SP), and the scarcity of alternative antimalarial drugs. AREAS COVERED: This review examines all the available information on IPT, in an aim to provide the scientific community with a framework to understand the benefits and limitations of this malaria control strategy. It includes the understanding of the historical background of the IPT strategy, the drug's mechanisms of actions, updated information on current available evidence, the implications of drug resistance and choice of alternative drugs, and a comprehensive discussion on the perspectives of IPT for malaria control in pregnant women and infants. EXPERT OPINION: IPT in pregnancy and infants is a cost-effective strategy that can contribute significantly to the control of malaria in endemic areas. Monitoring its effectiveness will allow tracking of progress, evaluation of the adequacy of currently used drugs and will highlight the eventual need for new therapies or alternative interventions. PMID- 22775554 TI - Elevated plasma levels and platelet-associated expression of the pro-thrombotic and pro-inflammatory protein, TNFSF14 (LIGHT), in sickle cell disease. AB - Chronic vascular inflammation and endothelial activation may initiate vaso occlusion in sickle cell disease (SCD). TNFSF14 (CD258; LIGHT), a recently identified pro-thrombotic and pro-inflammatory tumour necrosis factor (TNF) superfamily cytokine, has a potent activating effect on endothelial cells. We evaluated whether TNFSF14 production is altered in SCD and whether platelets contribute to this production. TNFSF14 was measured in platelet-free plasma from healthy-control individuals (CON), steady-state sickle cell anaemia (SCA), SCA on hydroxycarbamide therapy (SCAHC) and haemoglobin SC (HbSC) patients. Mean plasma TNFSF14 was significantly increased in SCA, SCAHC and HbSC, compared to CON individuals. In SCA/SCAHC patients, plasma TNFSF14, showed no correlation with haematological variables, but was significantly correlated with serum lactate dehydrogenase and inflammatory markers (CD40LG , IL8 and ICAM1). Platelet membrane TNFSF14 expression was significantly augmented on SCA platelets, and correlated with platelet activation; furthermore, measurement of platelet TNFSF14 release indicated that platelets may be a major source of circulating TNFSF14 in SCA. Interestingly, high plasma TNFSF14 was significantly associated with elevated tricuspid regurgitant velocity (>=2.5 m/s) in a population of SCA/SCAHC patients. The pro-inflammatory and atherogenic cytokine, TNFSF14, could contribute to endothelial activation and inflammation in SCA; future investigations may confirm whether this protein contributes to major clinical complications of the disease, such as pulmonary hypertension, and represents a potential therapeutic target. PMID- 22775555 TI - In vitro biocompatibility of a platinum-electrode embedded photosensitive polyimide (Durimide) retinal prosthesis. AB - PURPOSE: The photosensitive polyimide film, Durimide, is a common component of retinal prostheses; however, retinal cell response to Durimide has not been effectively studied This work assessed the in vitro biocompatibility of a retinal prosthesis containing platinum-electrode embedded Durimide film. MATERIALS AND METHODS: Biocompatibility evaluation assessed cytotoxicity, attachment, and proliferation of two cell lines: a human retinal pigmented epithelium cell line (CRL) and a rhesus monkey choroid- retinal endothelial cell line (RF/6A). Cells were cultured with the platinum-electrode embedded Durimide film, with tissue culture treated polystyrene plates (TCPS) used as a control substrate for cell growth. The effect of a Durimide-exposed medium on cell apoptosis and life cycle was assessed using flow cytometry (FCM). RESULTS: The indirect cytotoxicity evaluation revealed no toxic effect of the prosthesis on cells. The attachment and proliferation of CRL and RF/6A cells cultured with the Durimide prostheses showed no significant differences to the control. The FCM experiments demonstrated a liquid medium exposed to the prosthesis had no effects on apoptosis or cell life cycle in comparison with the control (p > 0.05). CONCLUSIONS: The results demonstrate that Durimide has good biocompatibility with retinal cell lines CRL and RF/6A. In conclusion, while further in vitro and in vivo studies are required to clarify long-term effects, Durimide is indicated as a promising material with suitable biocompatibility for retinal implants. PMID- 22775556 TI - Virtual reality as a screening tool for sports concussion in adolescents. AB - PRIMARY OBJECTIVE: There is controversy surrounding the cognitive effects of sports concussion. This study aimed to verify whether the technique of virtual reality could aid in the identification of attention and inhibition deficits in adolescents. STUDY DESIGN: A prospective design was used to assess 25 sports concussed and 25 non-sports-concussed adolescents enrolled in a sport and education programme. METHODS AND PROCEDURES: Participants were evaluated in immersive virtual reality via ClinicaVR: Classroom-CPT and in real life via the traditional VIGIL-CPT. MAIN OUTCOMES AND RESULTS: The neuropsychological assessment using virtual reality showed greater sensitivity to the subtle effects of sports concussion compared to the traditional test, which showed no difference between groups. The results also demonstrated that the sports concussion group reported more symptoms of cybersickness and more intense cybersickness than the control group. CONCLUSIONS: Sports concussion was associated with subtle deficits in attention and inhibition. However, further studies are needed to support these results. PMID- 22775557 TI - Conformation and chiral effects in alpha,beta,alpha-tripeptides. AB - Short alpha,beta,alpha-tripeptides comprising a central chiral trisubstituted beta(2,2,3)*-amino acid residue form unusual gamma-turns and delta-turns in CDCl(3) and DMSO-d(6) solutions but do not form beta-turns. Thermal coefficients of backbone amide protons, 2D-NMR spectra, and molecular modeling revealed that these motifs were strongly dependent on the configuration (chiral effect) of the central beta-amino acid residue within the triad. Accordingly, SSS tripeptides adopted an intraresidual gamma-turn like (C6) arrangement in the central beta amino acid, whereas SRS diastereomers preferred an extended delta-turn (C9) conformation. A different SRS-stabilizing bias was observed in the crystal structures of the same compounds, which shared the extended delta-turn (C9) found in solution, but incorporated an additional extended beta-turn (C11) to form an overlapped double turn motif. PMID- 22775558 TI - The genetics of primary and secondary sexual character trade-offs in a horned beetle. AB - When structures compete for shared resources, this may lead to acquisition and allocation trade-offs so that the enlargement of one structure occurs at the expense of another. Among the studies of morphological trade-offs, their importance has been demonstrated primarily through experimental manipulations and comparative analyses. Relatively, a few studies have investigated the underlying genetic basis of phenotypic patterns. Here, we use a half-sibling breeding design to determine the genetic underpinnings of the phenotypic trade-off between head horns and the male copulatory organ or aedeagus that has been found in the dung beetle Onthophagus taurus. Instead of the predicted negative genetic covariance among characters that trade-off, we find positive genetic covariance between absolute horn and aedeagus length and zero genetic covariance between relative horn and aedeagus length. Therefore, although the genetic covariance between absolute horn and aedeagus length would constrain the independent evolution of primary and secondary sexual characters in this population, there was no evidence of a trade-off. We discuss alternative hypotheses for the observed patterns of genetic correlation between traits that compete for resources and the implications that these have for selection and the evolution of such traits. PMID- 22775559 TI - Dispositional mindfulness moderates the effects of stress among adolescents: rumination as a mediator. AB - Recent research has demonstrated that higher levels of mindfulness are associated with greater psychological and physical health. However, the majority of this research has been conducted with adults; research is only beginning to examine the effects of mindfulness among adolescents. Further, research into adolescent mindfulness has typically conceptualized mindfulness as a unidimensional phenomenon and has not yet examined multidimensional models of mindfulness that have emerged in the adult literature. Further, the mechanisms through which mindfulness influences these outcomes are presently unclear. The present study examined the effects of three facets of mindfulness among adolescents. Seventy eight adolescents (61% female, 94% Caucasian, M age = 16) completed a measure of dispositional mindfulness at baseline. Participants then completed measures of daily stress, dysphoric affect, and state rumination over a 7-day period. Multilevel modeling analyses revealed that facets of mindfulness (i.e., nonreactivity and nonjudgment) were associated with lower levels of dysphoric mood. Mindfulness interacted with daily stress to predict later dysphoria; less mindful individuals were particularly vulnerable to the negative effects of stress. Finally, analyses demonstrated that the effect of the Mindfulness * Stress Moderation was significantly mediated by increases in daily rumination. These findings support the importance of mindfulness among adolescents and help to elucidate the mechanisms through which mindfulness influences psychological health. PMID- 22775560 TI - Sinonasal non-keratinizing squamous cell carcinoma with nasal skin extension as the initial presentation. AB - Sinonasal non-keratinizing squamous cell carcinoma (SCC), previously designated as transitional cell carcinoma or cylindrical cell carcinoma, is an uncommon malignant neoplasm with distinct histopathological features, considered to be a low-grade malignancy that usually occurs in elderly patients. Extensive local invasion is uncommon. Here we report a case of 90-year-old woman whose original presentation was as erythematous nasal skin nodules, biopsy of which showed a dermal tumor with features of sinonasal non-keratinizing SCC. No epidermal dysplasia was present. A subsequent computed tomography scan confirmed the presence of an endophytic tumor on the nasal sidewall. The initial presentation of sinonasal non-keratinizing SCC as a skin lesion is previously unreported to our knowledge. Diagnosis in this context requires accurate evaluation of the histopathology as well as a comprehensive knowledge of pathology specific to this anatomic location. PMID- 22775561 TI - Nanoglue: an alternative way to display cell-internalizing peptide at the spikes of hepatitis B virus core nanoparticles for cell-targeting delivery. AB - Cell-internalizing peptides (CIPs) can be used to mediate specific delivery of nanoparticles across cellular membrane. The objective of this study was to develop a display technique using hepatitis B virus (HBV) capsid-binding peptide as a "nanoglue" to present CIPs on HBV nanoparticles for cell-targeting delivery. A CIP was selected from a phage display library and cross-linked specifically at the tips of the spikes of the HBV capsid nanoparticle via the "nanoglue" by using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N hydroxysulfosuccinimide (sulfo-NHS). Fluorescent oligonucleotides packaged in the nanoparticles and the fluorescein molecules conjugated on the nanoparticles were delivered to cells by using this display technique. This study demonstrated a proof of principle for cell-targeting delivery via "nanoglue" bioconjugation. PMID- 22775562 TI - Clinical experience of tigecycline treatment in infections caused by extensively drug-resistant Acinetobacter spp. AB - BACKGROUND: Tigecycline has broad spectrum antimicrobial activity and is approved for complicated intra-abdominal infections, complicated skin and soft tissue infections, and community-acquired pneumonia. There are few data on clinical experience of tigecycline in hospital-acquired pneumonia (HAP) and Acinetobacter spp. infection. METHODS: A retrospective study was performed at eight hospitals in Korea from May 2009 to January 2010. Adult patients treated with tigecycline regardless of their source of infection or pathogens were enrolled. RESULTS: Tigecycline was administered in 108 patients. Pneumonia was the most common infection (43.5%), followed by skin and soft tissue infections (20.4%). Acinetobacter baumannii was isolated from 83 patients (76.9%) accounting for 50.3% of isolated pathogens, showing a resistance rate of 67.5% to carbapenems. Superinfection was identified in 32 patients (29.6%). Pseudomonas aeruginosa was most common microorganism causing superinfection (46.9%). Overall 30-day mortality rate was 52.9%. Thirty-day mortality rate of HAP and Acinetobacter spp. infection was 60.5% and 59.4%, respectively. CONCLUSION: Tigecycline can be considered as an alternative therapy in patients with HAP or infections caused by Acinetobacter spp., especially extensively drug-resistant A. baumannii. PMID- 22775563 TI - Proton NMR relaxation study on the nematic-nematic phase transition in A131 liquid crystal. AB - A study of the proton NMR spin-lattice relaxation time, T(1), of the A131 liquid crystal compound as a function of temperature and Larmor frequency, using a combination of fast field-cycling and standard NMR techniques, is presented. The frequency dispersion in a wide range (from 10 kHz to 300 MHz) at different temperatures and the temperature variation of T(1), in several frequency conditions, were analyzed considering the contributions of the molecular movements generally detected in liquid crystals. In the case of nematic phases of calamitic liquid crystals, the nuclear spin relaxation is dominated by collective movements and local molecular reorientations. The experimental results clearly show a transition within the nematic range of this compound, previously identified as one from the uniaxial to the biaxial phase. This transition can be associated with a slowing down of the molecular rotations around the long molecular axis, where the preferred orientation defines the principal director as detected in the T(1) dispersion analysis. PMID- 22775564 TI - Proton-coupled mechanochemical transduction: a mechanogenerated acid. AB - A novel mechanophore with acid-releasing capability is designed to produce a simple catalyst for chemical change in materials under mechanical stress. The mechanophore, based on a gem-dichlorocyclopropanated indene, is synthesized and used as a cross-linker in poly(methyl acrylate). Force-dependent rearrangement is demonstrated for cross-linked mechanophore samples loaded in compression, while the control shows no significant response. The availability of the released acid is confirmed by exposing a piece of insoluble compressed polymer to a pH indicator solution. The development of this new mechanophore is the first step toward force-induced remodeling of stressed polymeric materials utilizing acid catalyzed cross-linking reactions. PMID- 22775565 TI - Impaired function of gamma-delta lymphocytes in melanoma patients. AB - BACKGROUND: Melanoma is an immunogenic tumour but, despite the wide range of immunotherapies tested, only few promising results have been reported to date. Both in vitro and in xenograft models, gammadelta lymphocyte-mediated cytotoxicity against melanoma cells has been reported. IL-2/zoledronate treatment can expand gammadelta cells in vitro and in animal models. This could represent an immunotherapeutic strategy against melanoma. To evaluate the feasibility of this approach, we studied gammadelta lymphocyte phenotype from patients with melanoma, their ability to be expanded by IL-2/zoledronate and their cytotoxic activity against SK-MEL-30 cell line. MATERIALS AND METHODS: Peripheral blood samples were collected from 30 patients with melanoma and 10 healthy donors. Percentage of gammadelta lymphocytes and CD45RO+CD27+, CD45RA+CD27-, CD57+, Vgamma9Vdelta2 subpopulations were evaluated by flow cytometry. IL-2/zoledronate gammadelta cell expansion rate and their cytotoxicity against SK-MEL-30 cell line were studied. RESULTS: A percentage decrease in circulating Vgamma9Vdelta2 and an increase in CD45RA+CD27- and CD57+ gammadelta lymphocytes were observed in melanoma. IL-2/zoledronate expansion rate did not differ between controls and patients with melanoma but cytotoxicity against SK-MEL-30 appeared reduced. CONCLUSIONS: Our results show that gammadelta cell function is impaired in patients with advanced melanoma and suggest a possible role in tumour progression. PMID- 22775567 TI - Inhibition of GSK-3beta enhances neural differentiation in unrestricted somatic stem cells. AB - GSK-3beta is a key molecule in several signalling pathways, including the Wnt/beta-catenin signalling pathway. There is increasing evidence suggesting Wnt/beta-catenin signalling is involved in the neural differentiation of embryonic, somatic and neural stem cells. However, a large body of evidence indicates that this pathway maintains stem cells in a proliferative state. To address this controversy, we have investigated whether the Wnt/beta-catenin pathway is present and involved in the neural differentiation of newly introduced USSCs (unrestricted somatic stem cells). Our results indicate that the components of Wnt/beta-catenin signalling are present in undifferentiated USSCs. We also show that the treatment of neurally induced USSCs with BIO (6-bromoindirubin-3' oxime), a specific GSK-3beta inhibitor and Wnt activator, for 5 and 10 days results in increased expression of a general neuronal marker (beta-tubulin III). Moreover, the expression of pGSK-3beta and stabilized beta-catenin increased by BIO in neurally induced USSCs, indicates that the Wnt pathway is activated and functional in these cells. Thus, inhibition of GSK-3beta in USSCs enhances their neural differentiation, which suggests a positive role of the Wnt/beta-catenin signalling pathway towards neural fate. PMID- 22775566 TI - Reactive nitrogen species reactivities with nitrones: theoretical and experimental studies. AB - Reactive nitrogen species (RNS) such as nitrogen dioxide ((*)NO(2)), peroxynitrite (ONOO(-)), and nitrosoperoxycarbonate (ONOOCO(2)(-)) are among the most damaging species present in biological systems due to their ability to cause modification of key biomolecular systems through oxidation, nitrosylation, and nitration. Nitrone spin traps are known to react with free radicals and nonradicals via electrophilic and nucleophilic addition reactions and have been employed as reagents to detect radicals using electron paramagnetic resonance (EPR) spectroscopy and as pharmacological agents against oxidative stress mediated injury. This study examines the reactivity of cyclic nitrones such as 5,5-dimethylpyrroline N-oxide (DMPO) with (*)NO(2), ONOO(-), ONOOCO(2)(-), SNAP, and SIN-1 using EPR. The thermochemistries of nitrone reactivity with RNS and isotropic hfsc's of the addition products were also calculated at the PCM(water)/B3LYP/6-31+G**//B3LYP/6-31G* level of theory with and without explicit water molecules to rationalize the nature of the observed EPR spectra. Spin trapping of other RNS such as azide ((*)N(3)), nitrogen trioxide ((*)NO(3)), amino ((*)NH(2)) radicals and nitroxyl (HNO) were also theoretically and experimentally investigated by EPR spin trapping and mass spectrometry. This study also shows that other spin traps such as 5-carbamoyl-5-methyl-pyrroline N oxide, 5-ethoxycarbonyl-5-methyl-pyrroline N-oxide, and 5-(diethoxyphosphoryl)-5 methyl-1-pyrroline N-oxide can react with radical and nonradical RNS, thus making spin traps suitable probes as well as antioxidants against RNS-mediated oxidative damage. PMID- 22775569 TI - Cytology of a thyroid metastasis from an endometrial sarcoma: a case report. PMID- 22775568 TI - Serum biomarkers are similar in Churg-Strauss syndrome and hypereosinophilic syndrome. AB - RATIONALE: Churg-Strauss syndrome (CSS) and hypereosinophilic syndrome (HES) overlap considerably in clinical presentation. A reliable means of distinguishing between these groups of patients is needed, especially in the setting of glucocorticoid therapy. METHODS: A retrospective chart review of 276 adult subjects referred for evaluation of eosinophilia > 1500/MUl was performed, and subjects with a documented secondary cause of eosinophilia or a PDGFR -positive myeloproliferative neoplasm were excluded. The remaining subjects were assessed for the presence of American College of Rheumatology (ACR) criteria. Laboratory and clinical parameters were compared between subjects with biopsy-proven vasculitis (CSS; n = 8), >=4 ACR criteria (probable CSS; n = 21), HES with asthma and/or sinusitis without other CSS-defining criteria (HESwAS; n = 20), HES without asthma or sinusitis (HES; n = 18), and normal controls (n = 8). Serum biomarkers reported to be associated with CSS were measured using standard techniques. RESULTS: There were no differences between the subjects with definite or probable CSS or HES with respect to age, gender, or maintenance steroid dose. Serum CCL17, IL-8, and eotaxin levels were significantly increased in eosinophilic subjects as compared to normal controls, but were similar between the eosinophilic groups. Serum CCL17 correlated with eosinophil count (P < 0.0001, r = 0.73), but not with prednisone dose. CONCLUSIONS: In patients with a history of asthma and sinusitis, distinguishing between ANCA-negative CSS and PDGFR-negative HES is difficult because of significant overlap in clinical presentation and biomarker profiles. PMID- 22775570 TI - Dilated unroofed coronary sinus mimicking cor triatriatum in cardiac-type total anomalous pulmonary venous connection. AB - We present a rare case of a patient with a dilated unroofed coronary sinus mimicking cor triatriatum that altered mitral inflow in a cardiac-type total anomalous pulmonary venous connection. The membranous tissue in the left atrium, thought to be cor triatriatum tissue preoperatively, was actually a remnant of a dilated coronary sinus tissue. Although this tissue did not create a significant pressure gradient and merely induced a turbulent mitral inflow, we resected it to avoid future problems with mitral leaflet function. PMID- 22775571 TI - Infiltrating Foxp3+ regulatory T cells and histopathological features in canine classical and spermatocytic seminomas. AB - In humans, regulatory T (T reg) cells are known to play a critical role in both the regulation of immune homoeostasis and the progression of cancer. However, there is little information about the identification, characterization and the function of T reg cells in canine tumours. We identified T reg cells in 28 canine seminoma samples using a Forkhead box P3 (Foxp3) antibody and investigated the relationship between T reg cell infiltration and histopathological features of classical and spermatocytic seminomas (SE and SS, respectively). The Foxp3 protein showed nuclear immunostaining in infiltrating lymphocytes, and Foxp3+ cells were diffused or focally distributed in seminoma tissues. Foxp3+ cells were frequently present in the SS histotype, in seminomas that showed no evidence of tumour cell invasion into the vessels and in seminomas showing a diffuse growth pattern with three cell types. Neither the SE/SS histotype nor the histopathological features of the tumour correlated with Foxp3+ cell counts. These results indicate that Foxp3+ T reg cells may be associated with a less malignant histological phenotype or may not play a critical role in the immune response of canine seminomas. Moreover, Foxp3+ T reg cells may be associated with SS seminoma, but further studies, involving a larger number of samples, are required to better understand whether these cells play a critical role in the immune response in canine seminomas. This is the first report to demonstrate the characteristics of T reg cell infiltration in canine seminoma. PMID- 22775572 TI - Elevated TRIB2 with NOTCH1 activation in paediatric/adult T-ALL. AB - TRIB2 is a potent oncogene, elevated in a subset of human acute myeloid leukaemias (AML) with a mixed myeloid/lymphoid phenotype and NOTCH1 mutations. Although rare in AML, activating NOTCH1 mutations occur in 50% of all T cell acute lymphoblastic leukaemias (T-ALL). TRIB2 is a NOTCH1 target gene that functions in the degradation of key proteins and modulation of MAPK signalling pathways, implicated in haematopoietic cell survival and proliferation. This study showed that TRIB2 expression level is highest in the lymphoid compartment of normal haematopoietic cells, specifically in T cells. Analysis of TRIB2 expression across 16 different subtypes of human leukaemia demonstrated that TRIB2 expression was higher in ALL phenotypes versus all other phenotypes including AML, chronic lymphocytic leukaemia (CLL), myelodysplastic syndrome (MDS) and chronic myeloid leukaemia (CML). A T cell profile was distinguished by high TRIB2 expression in normal and malignant haematopoiesis. High TRIB2 expression was seen in T-ALL with normal karyotype and correlated with NOTCH signalling pathways. High TRIB2 expression correlated with NOTCH1/FBXW7 mutations in a paediatric T-ALL cohort, strongly linking NOTCH1 activation and high TRIB2 expression in paediatric T-ALL. The relationship between TRIB2 and T cell signalling pathways uniquely identifies leukaemia subtypes and will be useful in the advancement of our understanding of T cell and ALL biology. PMID- 22775573 TI - Letter to the editor. PMID- 22775574 TI - Linking fungal communities in roots, rhizosphere, and soil to the health status of Pisum sativum. AB - Changes in fungal communities associated with healthy and diseased pea roots were investigated using deep amplicon pyrosequencing in three spatial compartments: roots, rhizosphere, and surrounding soil. Thirty root systems were collected from three fields, half of which showing clear symptoms of root rot. In total, 500,461 internal transcribed spacer-1 sequences were obtained that were clustered into 123 (roots), 271 (rhizosphere), and 440 (bulk soil) nonsingleton operational taxonomic units (OTUs). Species richness was highest in bulk soils and lowest in roots; however, no notable differences in richness were observed between samples associated with diseased and healthy roots. Health status and field both had significant effects on fungal community structures in roots, whereas only field had significant effects on communities in rhizosphere and bulk soils. Indicator species analysis across the three fields identified a number of OTUs that were more abundant in healthy roots. Pathogens such as Fusarium oxysporum were abundant in diseased roots in some fields. Patterns of disease and causal agents of root rot were different among the three fields, which were also reflected in fungal communities. In conclusion, health status of roots was only vaguely reflected in rhizosphere and bulk soil fungal communities, whereas health status was more important for shaping root communities. PMID- 22775575 TI - Treatment strategies for myasthenia gravis: an update. AB - INTRODUCTION: New treatments for immune mediated diseases have increased notably in the last 10 years. Monoclonal antibodies directed against different components of the immune system have appeared, along with new drugs from the haematology field. In the case of myasthenia gravis (MG), many of these new treatments have been used in experimental animal models and also in patients. AREAS COVERED: This manuscript reviews the progress in the field of MG treatment achieved in the last 5 years. Firstly, our current treatment protocol is introduced. Secondly, new data from recent randomized trials and case series of patients treated with methotrexate, cyclophosphamide, rituximab or improved systems of apheresis is reported. Finally, all future treatments are discussed that are currently under evaluation in preclinical animal models of experimental autoimmune MG. EXPERT OPINION: Evidence supporting the use of methotrexate and rituximab in MG has been published recently, in addition to conflicting randomized trials that were not successful, evaluating the use of tacrolimus as a steroid sparing agent. New promising treatments are currently under evaluation in clinical trials, such as belimumab and eculizumab. PMID- 22775576 TI - Institutional peer support mediates the impact of physical declines on depressive symptoms of nursing home residents. AB - AIMS: This paper tests the mediating effect of institutional peer support on the relationship between physical declines and depressive symptoms among nursing home residents. BACKGROUND: As the number of older adults living in nursing homes increases, peer support received from other residents in the institutions is critical to the psychological well-being of residents who face physical declines and reduction in family support. This study tested whether institutional peer support would account for the detrimental effect of physical declines on depressive symptoms of Chinese older people residing in nursing homes. DESIGN: A cross-sectional design was used. METHOD: The study was conducted between January March 2009 by convenience sampling. The sample consisted of 187 nursing home residents, with 54 men and 133 women. Interviews were conducted by an experienced research assistant, and responses on physical abilities and institutional peer support were collected. Geriatric Depression Scale was used to assess depressive symptoms of each participant. RESULTS: Participants with poor physical abilities reported more depressive symptoms. Institutional peer support was negatively correlated with physical declines and depressive symptoms. Results of the regression analysis showed that the effect of physical declines on depressive symptoms was no longer significant when the influence of institutional peer support was statistically controlled, indicating a full mediation of institutional peer support on depression of older people. CONCLUSION: Findings of this study reveal that institutional peer support positively contributes to the psychological well-being of nursing home residents. PMID- 22775577 TI - Complex patterns of local adaptation in heat tolerance in Drosophila simulans from eastern Australia. AB - Latitudinal clines are considered a powerful means of investigating evolutionary responses to climatic selection in nature. However, most clinal studies of climatic adaptation in Drosophila have involved species that contain cosmopolitan inversion polymorphisms that show clinal patterns themselves, making it difficult to determine whether the traits or inversions are under selection. Further, although climatic selection is unlikely to act on only one life stage in metamorphic organisms, a few studies have examined clinal patterns across life stages. Finally, clinal patterns of heat tolerance may also depend on the assay used. To unravel these potentially confounding effects on clinal patterns of thermal tolerance, we examined adult and larval heat tolerance traits in populations of Drosophila simulans from eastern Australia using static and dynamic (ramping 0.06 degrees C min(-1)) assays. We also used microsatellites markers to clarify whether demographic factors or selection are responsible for population differentiation along clines. Significant cubic clinal patterns were observed for adult static basal, hardened and dynamic heat knockdown time and static basal heat survival in larvae. In contrast, static, hardened larval heat survival increased linearly with latitude whereas no clinal association was found for larval ramping survival. Significant associations between adult and larval traits and climatic variables, and low population differentiation at microsatellite loci, suggest a role for climatic selection, rather than demographic processes, in generating these clinal patterns. Our results suggest that adaptation to thermal stress may be species and life-stage specific, complicating our efforts to understand the evolutionary responses to selection for increasing thermotolerance. PMID- 22775578 TI - Cooperative catalysis approach to intramolecular hydroacylation. AB - Prior examples of hydroacylation to form six- and seven-membered ring ketones require either embedded chelating groups or other substrate design strategies to circumvent competitive aldehyde decarbonylation. A cooperative catalysis strategy enabled intramolecular hydroacylation of disubstituted alkenes to form seven- and six-membered rings without requiring substrate-embedded chelating groups. PMID- 22775580 TI - Anxiety and quality of life: clinically anxious children with and without autism spectrum disorders compared. AB - Comorbid anxiety disorders are common in children with autism spectrum disorders (ASD). However, studies comparing children with ASD to clinically anxious children are rare. This study investigated anxiety problems and health-related quality of life in children with high-functioning ASD and comorbid anxiety disorders (referred to as the ASD group), compared with children with anxiety disorders (referred to as the AD group). In total, 237 families participated; 115 children were in the ASD group (90 boys and 25 girls, M age = 11.37 years), and 122 children were in the AD group (62 boys and 60 girls, M age = 12.79 years). Anxiety disorders, anxiety symptoms, ASD-like symptoms, and health-related quality of life were assessed with the ADIS-C/P, SCARED-71, CSBQ, and EuroQol-5D, respectively. The number and types of anxiety disorders, as well as their severity, were similar in the ASD and AD groups; however, specific phobias were more common in the ASD group than in the AD group. As compared to the AD group, parents from the ASD group reported their children to have higher scores for total anxiety, social anxiety disorder, and panic disorder. More ASD-like behaviors and higher anxiety severity predicted a lower quality of life, irrespective of group. The results of this study support a highly similar phenotype of anxiety disorders in children with ASD; however, additional research is needed to examine the etiology and treatment effectiveness of anxiety disorders in children with ASD. PMID- 22775581 TI - Molecular characterization of Staphylococcus aureus in the United States 2004 2008 reveals the rapid expansion of USA300 among inpatients and outpatients. AB - To assess the clonal structure of Staphylococcus aureus in the United States, we performed a molecular epidemiological study of 1,055 S. aureus isolates from a nationally representative clinical isolate collection from 2004-2008. Resistant and susceptible isolates were typed with multilocus sequence typing, tested for the presence of Panton-Valentine leukocidin (PVL), and serotyped. USA300 (multilocus sequence typing clonal complex 8, PVL positive, and methicillin resistant) was the most frequently isolated clone, expanding from 12% of all isolates in 2004 to 38% in 2006. The USA300 clone increased significantly in frequency among both outpatients and inpatients. USA300 increased in both skin and soft-tissue and invasive infection isolates. The second most frequently observed clone was clonal complex 5, PVL-negative, and methicillin-resistant, and its frequency was stable from 2004-2008. The methicillin-susceptible S. aureus in the study was polyclonal, and decreased in frequency as it was replaced by USA300. PMID- 22775582 TI - Elevated left mid-frontal cortical activity prospectively predicts conversion to bipolar I disorder. AB - Bipolar disorder is characterized by a hypersensitivity to reward-relevant cues and a propensity to experience an excessive increase in approach-related affect, which may be reflected in hypo/manic symptoms. The present study examined the relationship between relative left-frontal electroencephalographic (EEG) activity, a proposed neurophysiological index of approach-system sensitivity and approach/reward-related affect, and bipolar course and state-related variables. Fifty-eight individuals with cyclothymia or bipolar II disorder and 59 healthy control participants with no affective psychopathology completed resting EEG recordings. Alpha power was obtained and asymmetry indices computed for homologous electrodes. Bipolar spectrum participants were classified as being in a major/minor depressive episode, a hypomanic episode, or a euthymic/remitted state at EEG recording. Participants were then followed prospectively for an average 4.7-year follow-up period with diagnostic interview assessments every 4 months. Sixteen bipolar spectrum participants converted to bipolar I disorder during follow-up. Consistent with hypotheses, elevated relative left-frontal EEG activity at baseline (a) prospectively predicted a greater likelihood of converting from cyclothymia or bipolar II disorder to bipolar I disorder over the 4.7-year follow-up period, (b) was associated with an earlier age-of-onset of first bipolar spectrum episode, and (c) was significantly elevated in bipolar spectrum individuals in a hypomanic episode at EEG recording. This is the first study to our knowledge to identify a neurophysiological marker that prospectively predicts conversion to bipolar I disorder. The fact that unipolar depression is characterized by decreased relative left-frontal EEG activity suggests that unipolar depression and vulnerability to hypo/mania may be characterized by different profiles of frontal EEG asymmetry. PMID- 22775583 TI - Effort-based decision-making in major depressive disorder: a translational model of motivational anhedonia. AB - Anhedonia is a core feature of major depressive disorder (MDD), but the precise nature of anhedonic symptoms is unknown. Whereas anhedonia has traditionally been viewed as a deficit in the experience of pleasure, more recent evidence suggests that reduced anticipation and motivation may also be a core feature of this symptom. Here, we provide data from a study in MDD patients and healthy controls using a translational measure of reward motivation, the Effort Expenditure for Rewards Task (EEfRT or "effort"). This task offers subjects a series of trials where they may choose to expend more or less effort for the opportunity to win varying amounts of monetary rewards. We found that MDD patients were less willing to expend effort for rewards than controls. Additionally, we observed that patients were less able to effectively use information about magnitude and probability of rewards to guide their choice behavior. Finally, within the MDD patient group, duration of the current episode was a significant negative predictor of EEfRT task performance. These findings offer novel support for theoretical models proposing that anhedonia in MDD may reflect specific impairments in motivation and reward-based decision-making. PMID- 22775584 TI - Desmin and CD34 positivity in cellular fibrous histiocytoma: an immunohistochemical analysis of 100 cases. AB - BACKGROUND: Cellular benign fibrous histiocytoma (CBFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH). Because of its relative monomorphism and frequent fascicularity, CBFH can easily be mistaken for a malignancy. In fact, CD34, often used to distinguish CBFH from dermatofibrosarcoma protuberans (DFSP), can also be positive. To add to the confusion, desmin positivity may also be observed in a subset of CBFH. Desmin and CD34 expression often cause interpretative difficulty which may lead to misdiagnosis. Our aim was to examine the incidence of desmin and CD34 expression in CBFH. METHODS: One hundred consecutive cases of morphologically typical CBFH were retrieved from consultation files. Clinicopathologic and immunohistochemical features were evaluated. RESULTS: SMA positivity was found in tumor cells in 93 of 100 cases (93%). Desmin positivity was found in 32 of 100 cases (32%). CD34 was positive in 6 of 100 cases (6%). There was no evident correlation between immunophenotype and anatomic site or other clinical variables. CONCLUSION: Frequent desmin (32%) and occasional CD34 (6%) expression are encountered in CBFH. Desmin positivity can be explained on the basis of myofibroblastic differentiation. The occasional CD34 positivity in a subset of CBFH should not be a deterrent from making the correct pathologic diagnosis, based on characteristic morphologic features. PMID- 22775585 TI - Binding of the J-binding protein to DNA containing glucosylated hmU (base J) or 5 hmC: evidence for a rapid conformational change upon DNA binding. AB - Base J (beta-D-glucosyl-hydroxymethyluracil) was discovered in the nuclear DNA of some pathogenic protozoa, such as trypanosomes and Leishmania, where it replaces a fraction of base T. We have found a J-Binding Protein 1 (JBP1) in these organisms, which contains a unique J-DNA binding domain (DB-JBP1) and a thymidine hydroxylase domain involved in the first step of J biosynthesis. This hydroxylase is related to the mammalian TET enzymes that hydroxylate 5-methylcytosine in DNA. We have now studied the binding of JBP1 and DB-JBP1 to oligonucleotides containing J or glucosylated 5-hydroxymethylcytosine (glu-5-hmC) using an equilibrium fluorescence polarization assay. We find that JBP1 binds glu-5-hmC DNA with an affinity about 40-fold lower than J-DNA (~400 nM), which is still 200 times higher than the JBP1 affinity for T-DNA. The discrimination between glu-5 hmC-DNA and T-DNA by DB-JBP1 is about 2-fold less, but enough for DB-JBP1 to be useful as a tool to isolate 5-hmC-DNA. Pre-steady state kinetic data obtained in a stopped-flow device show that the initial binding of JBP1 to glucosylated DNA is very fast with a second order rate constant of 70 MUM(-1) s(-1) and that JBP1 binds to J-DNA or glu-5-hmC-DNA in a two-step reaction, in contrast to DB-JBP1, which binds in a one-step reaction. As the second (slower) step in binding is concentration independent, we infer that JBP1 undergoes a conformational change upon binding to DNA. Global analysis of pre-steady state and equilibrium binding data supports such a two-step mechanism and allowed us to determine the kinetic parameters that describe it. This notion of a conformational change is supported by small-angle neutron scattering experiments, which show that the shape of JBP1 is more elongated in complex with DNA. The conformational change upon DNA binding may allow the hydroxylase domain of JBP1 to make contact with the DNA and hydroxylate T's in spatial proximity, resulting in regional introduction of base J into the DNA. PMID- 22775586 TI - Flawed processing of airborne EM data affecting hydrogeological interpretation. AB - Airborne electromagnetics (AEMs) is increasingly being used across the globe as a tool for groundwater and environmental management. Focus is on ensuring the quality of the source data, their processing and modeling, and the integration of results with ancillary information to generate accurate and relevant products. Accurate processing and editing of raw AEM data, the topic of this article, is one of the crucial steps in obtaining quantitative information for groundwater modeling and management. In this article, we examine the consequences that different levels of processing of helicopter transient electromagnetic method data have on the resulting electrical models and subsequently on hydrogeological models. We focus on different approaches used in the industry for processing of the raw data and show how the electrical resistivity-depth models, which is the end "geophysical" product (after data inversion) of an AEM survey, change with different levels of processing of the raw data. We then extend the study to show the impact on some of the hydrogeological parameters or models, which can be derived from the geophysical results. The consequences of improper handling of raw data to groundwater and environmental management can be significant and expensive. PMID- 22775587 TI - Optimization of a nanomedicine-based silicon phthalocyanine 4 photodynamic therapy (Pc 4-PDT) strategy for targeted treatment of EGFR-overexpressing cancers. AB - The current clinical mainstays for cancer treatment, namely, surgical resection, chemotherapy, and radiotherapy, can cause significant trauma, systemic toxicity, and functional/cosmetic debilitation of tissue, especially if repetitive treatment becomes necessary due to tumor recurrence. Hence there is significant clinical interest in alternate treatment strategies like photodynamic therapy (PDT) which can effectively and selectively eradicate tumors and can be safely repeated if needed. We have previously demonstrated that the second-generation photosensitizer Pc 4 (silicon phthalocyanine 4) can be formulated within polymeric micelles, and these micelles can be specifically targeted to EGFR overexpressing cancer cells using GE11 peptide ligands, to enhance cell-specific Pc 4 delivery and internalization. In the current study, we report on the in vitro optimization of the EGFR-targeting, Pc 4 loading of the micellar nanoformulation, along with optimization of the corresponding photoirradiation conditions to maximize Pc 4 delivery, internalization, and subsequent PDT-induced cytotoxicity in EGFR-overexpressing cells in vitro. In our studies, absorption and fluorescence spectroscopy were used to monitor the cell-specific uptake of the GE11-decorated Pc 4-loaded micelles and the cytotoxic singlet oxygen production from the micelle-encapsulated Pc 4, to determine the optimum ligand density and Pc 4 loading. It was found that the micelle formulations bearing 10 mol % of GE11-modified polymer component resulted in the highest cellular uptake in EGFR-overexpressing A431 cells within the shortest incubation periods. Also, the loading of ~ 50 MUg of Pc 4 per mg of polymer in these micellar formulations resulted in the highest levels of singlet oxygen production. When formulations bearing these optimized parameters were tested in vitro on A431 cells for PDT effect, a formulation dose containing 400 nM Pc 4 and photoirradiation duration of 400 s at a fluence of 200 mJ/cm(2) yielded close to 100% cell death. PMID- 22775588 TI - Assessment of executive functioning in brain injury: collaboration between speech language pathology and neuropsychology for an integrative neuropsychological perspective. AB - BACKGROUND: Executive functioning (EF) deficits are common sequelae of traumatic brain injury (TBI). These deficits extend beyond the acute stages of recovery and pose a significant challenge in rehabilitation efforts. Current theories of EF propose a multidimensional construct. This paper provides an integrative theoretical framework with interactive dimensions for the assessment and treatment of EF that can assist the interdisciplinary team to successfully manage EF deficits secondary to TBI. METHODS: This paper is a review of pertinent literature related to assessment of EF. It concludes with a case presentation that illustrates the utility of the proposed theoretical framework in the rehabilitation context. CONCLUSIONS: Formal neuropsychological, standardized psychometric measures and informal clinical observations, particularly as they relate to contextual assessment, should be incorporated in order to effectively assess EF difficulties in survivors of TBI. The paper concludes with recommendations for effective assessment and treatment of EF by the interdisciplinary team consisting of speech-language pathologists and neuropsychologists. PMID- 22775589 TI - Can platelet BACE1 levels be used as a biomarker for Alzheimer's disease? Proof of-concept study. AB - To date there is no validated peripheral biomarker to assist with the clinical diagnosis of Alzheimer's disease (AD). Platelet proteins have been studied as AD biomarkers with relative success. In this study, we investigated whether platelet BACE1 levels differ between AD and cognitively normal (CN) control patients. Using a newly developed ELISA method, we found that BACE1 levels were significantly lower in AD compared to CN subjects. These data were supported by the observation that several BACE1 isoforms, identified by Western blotting, were also lower in AD platelets. This proof-of-concept study provides evidence for testing platelet BACE1 levels as a peripheral AD biomarker using a novel, sensitive and inexpensive method. PMID- 22775590 TI - Immediate placement and restoration of implants in the aesthetic zone with a trimodal approach: soft tissue alterations and its relation to gingival biotype. AB - PURPOSE: The aim of this prospective study was to evaluate the soft tissue changes around implants in the aesthetic zone, placed under a trimodal approach (immediate post-extraction placement, flapless, and immediate provisional restoration) and its relationship to gingival/periodontal biotype of the patient. MATERIALS AND METHODS: The sample consisted of 14 patients from two private practices that were in need of a tooth extraction in the anterior maxillary region (cuspid to cuspid) and were candidates to a replacement with a dental implant. An initial measurement (baseline) of the position or the mesial and distal papillae and gingival zenith was made at this time, with a rigid dental supported stent and an electronic precision caliper, able to the second tenth of a millimeter; after careful tooth extraction, the periodontal thickness, at a point 5 mm apical to de gingival buccal margin, with an analogical thickness gauge, able to one tenth of a millimeter. Once the implant was inserted an immediate provisional restoration was delivered. To evaluate the soft tissue changes measurements were repeated at 3, 6, and 12 months. A statistical analysis was performed to evaluate the changes in the gingival margin around the implant restorations and to identify a possible correlation to patient's periodontal thickness. RESULTS: All 14 patients received Straumann ((r)) implants (9 Tissue Level [TL] Regular Neck [RN], 2 TL Narrow Neck [NN], 2 Bone Level [BL] Narrow Crossfit [NC], and 1 BL Regular Crossfit [RC]). All implants integrated and none had any biological complications. Three provisional restorations presented screw loosening and retightened once and one loss retention and was recemented once. In one patient, with a severe bruxing habit, the final restoration suffered screw loosening and was retightened. Of the final restorations, 12 were screw-retained and 2 cemented on custom-made Zirconia abutments. A mean recession of the buccal margin of 0.45 mm was recorded at 12 months ( +/- 0.25 mm). An acceptable papilla level was present in all cases at 1 year, with mean changes of 0.38 mm ( +/- 0.60) for the mesial and 0.80 mm ( +/- 0.90) of the distal papilla, respectively. No correlation could be established between the soft tissue changes and the periodontal biotype of the patient. CONCLUSIONS: Within the limitations of this study, the good aesthetic outcome and minimal complications seem to validate the trimodal approach protocol as a reliable and simple protocol to place and restore immediate implants in the aesthetic zone. No correlation between the patient's gingival biotype and the soft tissue alterations could be established. Additional studies are needed to verify long-term aesthetic results with this approach and to better define and quantify biotypes. PMID- 22775591 TI - Training and tailored outreach support to improve alcohol screening and brief intervention in Aboriginal Community Controlled Health Services. AB - INTRODUCTION AND AIMS: Aboriginal Community Controlled Health Services (ACCHSs) are often the primary point of contact for Indigenous Australians experiencing alcohol-related harms. Screening and brief intervention (SBI) is a cost-effective treatment for reducing these harms. Factors influencing evidence-based alcohol SBI delivery in ACCHSs have been identified. Evaluations of strategies targeting these factors are required. The aim of this paper is to quantify the effect of training and tailored outreach support on the delivery of alcohol SBI in four Aboriginal Community Controlled Health Services (ACCHSs). DESIGN AND METHODS: A pre- post- assessment of alcohol information recorded in computerised patient information systems of four ACCHSs. RESULTS: For ACCHSs combined there was a statistically significant increase in the proportion of eligible clients with an electronic record of any alcohol information (3.2% to 7.5%, P < 0.0001) and a valid alcohol screen (1.6% to 6.5%, P < 0.0001), and brief intervention (25.75% to 47.7%, P < 0.0001). All four ACCHSs achieved statistically significant increases in the proportion of clients with a complete alcohol screen (10.3%; 7.4%; 2%, P < 0.0001 and 1.3%, P < 0.05), and two in the proportion with a heavy drinking screen (7% and 3.1%, P < 0.0001). DISCUSSION AND CONCLUSIONS: Implementing evidence-based alcohol SBI in ACCHSs is likely to require multiple strategies tailored to the characteristics of specific services. Outreach support provided by local drug and alcohol practitioners and a one item heavy drinking screen offer considerable promise for increasing routine alcohol SBI delivery in ACCHSs. Training and outreach support appear to be effective for achieving modest improvements in alcohol SBI delivery in ACCHSs. PMID- 22775755 TI - Nuclear morphology and c-Jun N-terminal kinase 1 expression differentiate serum starved oxidative stress signalling from hydrogen peroxide-induced apoptosis in retinal neuronal cell line. AB - Oxidative stress induced by serum starvation and H2O2 exposure, both triggers apoptosis in retinal neuronal cell line RGC-5 (retinal ganglion cell-5). We have examined whether, despite excess generation of ROS (reactive oxygen species) and apoptosis induction, there is any dissimilarity in nuclear morphology and apoptotic signalling pathway in RGC-5 under these conditions. Sub-confluent cells were treated either with H2O2 or maintained in SFM (serum-free medium). ROS level was detected along with nuclear morphology and ultrastructural analysis. Generation of excess intracellular ROS, nuclear localization of Bax and caspase 3 activation along with decrease of cellular viability, confirmed apoptosis induction in RGC-5 by 72 h serum starvation and 500 M H2O2 exposure for 1 h. Nuclear swelling as supported by nuclear cytoplasmic ratio and conspicuous black spots with nuclear remodelling were observed only upon SFM, but not with H2O2 treatment. Serum starvation did not alter JNK1 (c-Jun N-terminal kinase 1) expression, although nuclear translocation and higher level of pJNK (phospho-JNK) was evident. Conversely, H2O2 exposure blocked the expression and activation of JNK1 to phospho-JNK as a negligible level of pJNK was present in the cytoplasm. Despite similar ROS generation in both the conditions, difference in nuclear morphology and JNK1 expression leads to the hypothesis that RGC-5 cells may follow different signalling pathways when challenged with serum starvation and H2O2. PMID- 22775756 TI - Dynamical features in cationic micelles of varied chain length. AB - Chain length is one of the parameters controlling the structural arrangement of micelle monomers, such that one can tailor the monomers for different applications, but the effect of chain length on the dynamical behavior of micelles is unknown. In this article, we report a study on the effect of varying chain length on the dynamical behavior of alkyltrimethylammonium bromide (C(n)TAB) micelles (n = 10, 12, 14, and 16) using incoherent quasielastic neutron scattering (QENS). The data analysis clearly shows the presence of two distinct motions: global motion of whole micelles and faster internal motions of the C(n)TAB monomers. The global diffusion is Fickian in nature, whereas the internal motions can be described with a model that considers the motions of the headgroup and the hydrophobic alkyl chain separately. Methyl groups in the headgroup undergo 3-fold jump rotations, and the hydrogen atoms belonging to the alkyl chain undergo localized translational diffusion. The hydrogen atoms belonging to the alkyl chain are confined within spherical volumes that increase linearly along the C(n)TAB chain: the hydrogen atoms closer to the headgroup move within smaller spheres with lower diffusion coefficients than those farther from the headgroup. The main result is that, with increasing chain length, the dynamics of the C(n)TAB monomer is greatly affected: diffusion is reduced and occurs in smaller spheres, and residence times are increased. Global motion is also hindered with increased chain length. PMID- 22775757 TI - What we can learn from sushi: a review on seaweed-bacterial associations. AB - Many eukaryotes are closely associated with bacteria which enable them to expand their physiological capacities. Associations between algae (photosynthetic eukaryotes) and bacteria have been described for over a hundred years. A wide range of beneficial and detrimental interactions exists between macroalgae (seaweeds) and epi- and endosymbiotic bacteria that reside either on the surface or within the algal cells. While it has been shown that these chemically mediated interactions are based on the exchange of nutrients, minerals, and secondary metabolites, the diversity and specificity of macroalgal-bacterial relationships have not been thoroughly investigated. Some of these alliances have been found to be algal or bacterial species-specific, whereas others are widespread among different symbiotic partners. Reviewing 161 macroalgal-bacterial studies from the last 55 years, a definite bacterial core community, consisting of Gammaproteobacteria, CFB group, Alphaproteobacteria, Firmicutes, and Actinobacteria species, seems to exist which is specifically (functionally) adapted to an algal host-associated lifestyle. Because seaweed-bacterial associations are appealing from evolutionary and applied perspectives, future studies should integrate the aspects of diverse biological fields. PMID- 22775758 TI - Overview of metformin: special focus on metformin extended release. AB - INTRODUCTION: Diabetes is characterized by chronic hyperglycemia and vascular alterations, leading to micro-vascular and macro-vascular complications, which account for increased morbidity and mortality associated with the disease. Cardiovascular complications are the leading cause of death in patients with diabetes. Due to its cardio-protective effects, metformin is recommended as the initial agent of choice in the treatment of T2DM. Results of UKPDS, one of the largest and longest studies, showed reductions in cardiovascular mortality in patients using metformin. AREAS COVERED: This article reviews the history, structure, pharmacokinetics, clinical efficacy, and safety of extended-release metformin (XR). It also highlights fact that its use has been shown to have the same clinical and metabolic benefits as standard metformin, but also improved adherence and reduced side effects. The paper provides a side-by-side comparison of the main differences in the use of metformin XR versus metformin IR, i.e., their effect on lipids, and gastrointestinal (GI) side effects. Studies included in this review were selected from PUBMED and Embase databases. EXPERT OPINION: Given the chronic nature of diabetes, patient's adherence to therapy is very important in preventing complications of the disease. Compliance with the standard metformin formulation can be poor, due to multiple daily dosing and frequent GI side effects. Metformin XR can be given once daily and is associated with less GI side effects compared to immediate release metformin (IR); This leads to increased compliance, improved glycemic control and hence decreased risk of the associated micro- and macro-vascular complications. PMID- 22775759 TI - Determining behavioral factors for interventions to increase safe water consumption: a cross-sectional field study in rural Ethiopia. AB - In developing countries, the lack of safe water options leads to many health risks. In the Ethiopian Rift Valley, most water sources are contaminated with an excess of fluoride. The consumption of fluoride-contaminated water leads to dental and skeletal fluorosis. The article presents an approach to designing community interventions based on evidence from quantitative data. After installing a community filter, a baseline study was conducted in 211 households to survey the acceptance and usage of the filter. To identify important psychological factors that lead to health behavior change, the Risk, Attitude, Norm, Ability, Self-regulation (RANAS) model was taken into account. Descriptive statistics were calculated for behavioral determinants, and their influence on consumption was analyzed with a linear regression. For every behavioral factor, an intervention potential (IP) was calculated. It was found that perceived distance, factual knowledge, commitment, and taste strongly influenced participants' consumption behavior and therefore should be tackled for interventions. PMID- 22775761 TI - Variation: use it or misuse it - replication and its variants. PMID- 22775760 TI - Erythrocyte-derived ATP and perfusion distribution: role of intracellular and intercellular communication. AB - In complex organisms, both intracellular and intercellular communication are critical for the appropriate regulation of the distribution of perfusion to assure optimal O(2) delivery and organ function. The mobile erythrocyte is in a unique position in the circulation as it both senses and responds to a reduction in O(2) tension in its environment. When erythrocytes enter a region of the microcirculation in which O(2) tension is reduced, they release both O(2) and the vasodilator, ATP, via activation of a specific and dedicated signaling pathway that requires increases in cAMP, which are regulated by PDE3B. The ATP released initiates a conducted vasodilation that results in alterations in the distribution of perfusion to meet the tissue's metabolic needs. This delivery mechanism is modulated by both positive and negative feedback regulators. Importantly, defects in low O(2) -induced ATP release from erythrocytes have been observed in several human disease states in which impaired vascular function is present. Understanding of the role of erythrocytes in controlling perfusion distribution and the signaling pathways that are responsible for ATP release from these cells makes the erythrocyte a novel therapeutic target for the development of new approaches for the treatment of vascular dysfunction. PMID- 22775762 TI - Differential concentration and time dependent effects of progesterone on kinase activity, hyperactivation and acrosome reaction in human spermatozoa. AB - Progesterone has been identified to be one of the physiological regulators of sperm hyperactivation and acrosome reaction. However, the high sensitivity of human spermatozoa to progesterone implies that many may undergo premature hyperactivation and acrosome reaction thereby compromising their ability to fertilize. We hypothesized that if a spermatozoon has to preclude the occurrence of these events prematurely, there should be differential dose- and time dependent effects on motility and acrosome reaction. We observed that low concentrations of progesterone (10 and 100 nm) induce sperm motility and activate tyrosine kinase; higher concentrations (1-10 MUm) are required to induce extracellular signal regulated kinases 1/2 (Erk1/2), p90 ribosomal S6 kinase (p90RSK), p38 mitogen-activated protein kinase (p38MAPK), c-Jun N-terminal kinase (JNK1) and AKT phosphorylation, hyperactivation and acrosome reaction. The induction of acrosome reaction and tyrosine phosphorylation in response to higher concentration of progesterone is not absolutely dependent on activation of T-type voltage-gated Ca(2+) channel or CatSper as Mibefradil did not completely abrogate progesterone-mediated effects. These results imply that although the spermatozoa are sensitive to low concentrations of progesterone, they only activate motility and tyrosine kinase activation; higher concentrations are required to induce hyperactivation and acrosome reaction probably by activating multiple kinase pathways including the MAPK and AKT. PMID- 22775763 TI - Inadequacy of cardiovascular risk factor management in chronic kidney transplantation - evidence from the FAVORIT study. AB - BACKGROUND: Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD). Our objective is to describe the prevalence of CVD risk factors applying standard criteria and use of CVD risk factor-lowering medications in contemporary KTRs. METHODS: The Folic Acid for Vascular Outcome Reduction in Transplantation study enrolled and collected medication data on 4107 KTRs with elevated homocysteine and stable graft function an average of five yr post-transplant. RESULTS: CVD risk factors were common (hypertension or use of blood pressure (BP) lowering medication in 92%, borderline or elevated low density lipoprotein (LDL) or use of lipid-lowering agent in 66%, history of diabetes mellitus in 41%, and obesity in 38%); prevalent CVD was reported in 20% of study participants. National Kidney Foundation BP guidelines (BP <130/80 mmHg) were not met by 69% of participants. Uncontrolled hypertension (BP of 140/90 mmHg or higher) was present in 44% of those taking antihypertension medication; 18% of participants had borderline or elevated LDL, of which 60% were untreated, and 31% of the participants with prevalent CVD were not using an antiplatelet agent. CONCLUSION: There is opportunity to improve treatment and control of traditional CVD risk factors in kidney transplant recipients. PMID- 22775764 TI - Immunohistochemical, tomographic, and histological study on onlay bone graft remodeling. Part III: allografts. AB - OBJECTIVE: In the last decades aroused the interest for bone tissue bank as an alternative to autogenous grafting, avoiding donor sites morbidity, surgical time, and costs reduction. The purpose of the study was to compare allografts (ALg) with autografts (AUg) using histology, immunochemistry, and tomographic analysis. MATERIAL AND METHODS: Fifty-six New Zealand White rabbits were submitted to surgical procedures. Twenty animals were donors and 36 were actually submitted to onlay grafting with ALg (experimental group) and AUg (control group) randomly placed bilaterally in the mandible. Six animals of each group were sacrificed at 3, 5, 7, 10, 20, and 60 postoperative days. Immunolabeling was accomplished with osteoprotegerin (OPG); receptor activator of nuclear factor-k ligand (RANKL); alkaline phosphatase (ALP); osteopontin (OPN); vascular endothelial growth factor (VEGF); tartrate-resistant acid phosphatase (TRAP); collagen type I (COL I); and osteocalcin (OC). Density and volume of the grafts was evaluated on tomography obtained at the surgery and sacrifice. RESULTS: The ALg and AUg exhibited similar patterns of density and volume throughout the experiments. The intra-group data showed statistical differences at days 7 and 60 in comparison with other time points (P = 0.001), in both groups. A slight graft expansion from fixation until day 20 (P = 0.532) was observed in the AUg group and then resorbed significantly at the day 60 (P = 0.015). ALg volume remained stable until day 7 and decreased at day 10 (P = 0.045). The light microscopy analysis showed more efficient incorporation of AUg onto the recipient bed if compared with the ALg group. The immunohistochemical labeling picked: at days 10 and 20 with OPG in the AUg group and at day 7 with TRAP in the ALg group (P = 0.001 and P = 0.002, respectively). CONCLUSIONS: ALg and AUg were not differing in patterns of volume and density during entire experiment. Histological data exhibit more efficient AUg incorporation into recipient bed compared with the ALg group. Immunohistochemistry outcomes demonstrated similar pattern for both ALg and AUg groups, except for an increasing resorption activity in the ALg group mediated by TRAP and in the AUg group by higher OPG labeling. However, this latter observation does not seem to influence clinical outcomes. PMID- 22775765 TI - Vitrification of immature feline oocytes with a commercial kit for bovine embryo vitrification. AB - The aim of this study was to evaluate the suitability of a commercial kit for bovine embryo vitrification for cryopreserving cat oocytes and to evaluate comparatively the effects of its use with slow freezing procedure on cryotolerance in terms of morphology and oocyte resumption of meiosis. Germinal vesicle stage oocytes isolated from cat ovaries were either vitrified (n = 72) using a vitrification kit for bovine embryo or slow frozen (n = 69) by exposing oocyte to ethylene glycol solution before being transferred to a programmable embryo freezer. After thawing and warming, oocytes were cultured for 48 h and then were examined for meiosis resumption using bisbenzimide fluorescent staining (Hoechst 33342). Fresh immature oocytes (n = 92) were used as the control group. The proportion of oocytes recovered in a morphologically normal state after thawing/warming was significantly higher in frozen oocytes (94.5%) than in the vitrified ones (75%, p < 0.01). Morphological integrity after culture was similar in vitrified (73.6%) and slow frozen oocytes (76.8%); however, only 37.5% of the morphologically normal oocytes resumed meiosis after vitrification compared to 60.9% of those submitted to slow freezing procedure (p < 0.01). Fresh oocytes showed higher morphological integrity (91.3%) and meiosis resumption rates (82.6%, p < 0.002) than cryopreserved oocytes, irrespective of the procedure used. These results suggest that immature cat oocytes vitrified with a kit for bovine embryos retain their capacity to resume meiosis after warming and culture, albeit at lower rates than slow frozen oocytes. Vitrification and slow freezing methods show similar proportions of oocytes with normal morphology after culture, which demonstrate that thawed and warmed oocytes that resist to cryodamage have the same chances to maintain their integrity after 48 h of culture. PMID- 22775766 TI - Generational diversity: what nurse managers need to know. AB - AIM: This article presents a discussion of generational differences and their impact on the nursing workforce and how this impact affects the work environment. BACKGROUND: The global nursing workforce represents four generations of nurses. This generational diversity frames attitudes, beliefs, work habits and expectations associated with the role of the nurse in the provision of care and in the way the nurse manages their day-to-day activities. DATA SOURCES: An electronic search of MEDLINE, PubMed and Cinahl databases was performed using the words generational diversity, nurse managers and workforce. The search was limited to 2000-2012. DISCUSSION: Generational differences present challenges to contemporary nurse managers working in a healthcare environment which is complex and dynamic, in terms of managing nurses who think and behave in a different way because of disparate core personal and generational values, namely, the three Cs of communication, commitment and compensation. IMPLICATIONS FOR NURSING: An acceptance of generational diversity in the workplace allows a richer scope for practice as the experiences and knowledge of each generation in the nursing environment creates an environment of acceptance and harmony facilitating retention of nurses. CONCLUSION: Acknowledgement of generational characteristics provides the nurse manager with strategies which focus on mentoring and motivation; communication, the increased use of technology and the ethics of nursing, to bridge the gap between generations of nurses and to increase nursing workforce cohesion. PMID- 22775767 TI - An accurate and reliable real time SNP genotyping assay for the HLA-G +3142 bp C>G polymorphism. AB - Human leukocyte antigen (HLA)-G is a non classical HLA class I antigen with immuno-modulatory functions. The HLA-G gene is characterized by a +3142C>G variant in the 3' untranslated region which is suggested to control protein production and to be associated with pathological conditions. DNAs form 221 randomly selected healthy subjects were genotyped for HLA-G +3142C>G polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) (BaeGI), real-time PCR and sequencing. The 19% of the PCR-RFLP heterozygous samples were genotyped as 3142GG by real-time PCR and sequencing. This disagreement is caused by digestion efficiency in PCR-RFLP. This real-time PCR method will guarantee an accurate genotyping for future research and clinical purposes, where large cohorts should be tested. PMID- 22775769 TI - Neurocognitive development in 5- to 16-year-old North American children: a cross sectional study. AB - Executive functions are thought to be the latest functions to mature. However, this view has not been tested by assessing simultaneously memory, perception of emotions, visuospatial perception, and visuoconstructional skills. NEPSY II norm data from 1000 5- to 16-year-old U.S. children were obtained. Fifteen NEPSY II subtests with no floor or ceiling effects in any age group and no major changes in task type were selected. The 16-year level was attained at age 12 to 13 in all subtests with two exceptions: social perception (age 10 to 11) and narrative memory (age 14). Trend analyses showed that development was rapid in the age range 5 to 9 years followed by a deceleration in the rate of development. Peak performances were reached at 14 to 16 years but later in some subtests representing executive functions, verbal memory, and visuospatial performance. Thus, the study specified developmental time tables of neurocognitive functions. It demonstrated that not only executive functions but also verbal memory and visuospatial performance continue to develop beyond age 16. PMID- 22775770 TI - Regioselective double hydrophosphination of terminal arylacetylenes catalyzed by an iron complex. AB - The first catalytic double hydrophosphination of alkynes was achieved by reaction with diarylphosphines in the presence of an iron catalyst. The double hydrophosphination proceeded regioselectively and effectively for various secondary arylphosphines and terminal alkynes to give 1,2-bisphosphinoethane derivatives. PMID- 22775771 TI - Profiles of executive functioning: associations with substance dependence and risky sexual behavior. AB - The present investigations applied a theoretical perspective regarding the impact of executive functioning (EF) on sexual risk among substance users, using a methodological approach designed to examine whether EF subtypes differentially predict behavior patterns. Participants included 104 substance-using HIV-negative gay and bisexual men. Participants completed 5 neuropsychological assessment tasks selected to tap discrete EF components, and these data were linked to data on substance dependence and behavioral reports of substance use and sexual risk in the past 30 days. Cluster analysis identified 3 EF subtypes: (a) high performing (good performance across all measures); (b) low performing (poor performance across all measures); and (c) poor IGT performance (impairment on the Iowa Gambling Task [IGT] and its variant, but good performance on all other tasks). The 3 subtypes did not differ in amount of substance use, but the low performing subtype was associated with greater rates of substance dependence. The low-performing subtype reported the highest rates of sexual behavior and risk, while the poor-IGT-performance subtype reported the lowest rates of sexual risk taking. Global associations between substance use and sexual risk were strongest among the low-performing subtype, but event-level associations appeared strongest among individuals in the high-performing subtype. These data suggest complex associations between EF and sexual risk among substance users, and suggest that the relationship between substance use and sexual risk may vary by EF subtypes. PMID- 22775774 TI - Tandem ring-opening decarboxylation of cyclopropane hemimalonates with sodium azide: a short route to gamma-aminobutyric acid esters. AB - Cyclopropane hemimalonates, when treated with sodium azide, undergo a tandem ring opening decarboxylation to produce gamma-azidobutyric acids in good yields. These adducts were hydrogenated to form gamma-aminobutyric acid (GABA) methyl esters. PMID- 22775772 TI - Functional brain networks associated with cognitive control, cocaine dependence, and treatment outcome. AB - Individuals with cocaine dependence often evidence poor cognitive control. The purpose of this exploratory study was to investigate networks of functional connectivity underlying cognitive control in cocaine dependence and examine the relationship of the networks to the disorder and its treatment. Independent component analysis (ICA) was applied to fMRI data to investigate if regional activations underlying cognitive control processes operate in functional networks, and whether these networks relate to performance and treatment outcome measures in cocaine dependence. Twenty patients completed a Stroop task during fMRI prior to entering outpatient treatment and were compared to 20 control participants. ICA identified five distinct functional networks related to cognitive control interference events. Cocaine-dependent patients displayed differences in performance-related recruitment of three networks. Reduced involvement of a "top-down" fronto-cingular network contributing to conflict monitoring correlated with better treatment retention. Greater engagement of two "bottom-up" subcortical and ventral prefrontal networks related to cue-elicited motivational processing correlated with abstinence during treatment. The identification of subcortical networks linked to cocaine abstinence and cortical networks to treatment retention suggests that specific circuits may represent important, complementary targets in treatment development for cocaine dependence. PMID- 22775775 TI - Pulmonary embolism and intra-aortic thrombosis in essential thrombocythaemia. PMID- 22775773 TI - Retraining the addicted brain: a review of hypothesized neurobiological mechanisms of mindfulness-based relapse prevention. AB - Addiction has generally been characterized as a chronic relapsing condition (Leshner, 1999). Several laboratory, preclinical, and clinical studies have provided evidence that craving and negative affect are strong predictors of the relapse process. These states, as well as the desire to avoid them, have been described as primary motives for substance use. A recently developed behavioral treatment, mindfulness-based relapse prevention (MBRP), was designed to target experiences of craving and negative affect and their roles in the relapse process. MBRP offers skills in cognitive-behavioral relapse prevention integrated with mindfulness meditation. The mindfulness practices in MBRP are intended to increase discriminative awareness, with a specific focus on acceptance of uncomfortable states or challenging situations without reacting "automatically." A recent efficacy trial found that those randomized to MBRP, as compared with those in a control group, demonstrated significantly lower rates of substance use and greater decreases in craving following treatment. Furthermore, individuals in MBRP did not report increased craving or substance use in response to negative affect. It is important to note, areas of the brain that have been associated with craving, negative affect, and relapse have also been shown to be affected by mindfulness training. Drawing from the neuroimaging literature, we review several plausible mechanisms by which MBRP might be changing neural responses to the experiences of craving and negative affect, which subsequently may reduce risk for relapse. We hypothesize that MBRP may affect numerous brain systems and may reverse, repair, or compensate for the neuroadaptive changes associated with addiction and addictive-behavior relapse. PMID- 22775776 TI - New insights into family functioning and quality of life after pediatric liver transplantation. AB - Thorough research of the medical aspects of pediatric liver transplantation has given way to recent interest in the impact of the transplantation process on the QOL of recipients and their families. In this cross-sectional study, we compared the family functioning and QOL of children (n = 30) aged between three and 16 yr (M = 10.10, s.d. = 3.62) who had received a liver transplant in the previous 1-12 yr (M = 5.31, s.d. = 3.44) with non-transplant children (n = 33), as reported via parent proxy. Results showed that parents of pediatric liver transplant recipients made significantly more adjustments to family routines to accommodate their children, particularly in relation to childcare. Impaired family functioning was also found to be associated with decreased QOL. These preliminary findings of relative deficits in family functioning may inform psychosocial interventions to assist pediatric liver transplant patients and their families. Further investigation beyond a single-center study incorporating subjective information from pediatric patients and their parents is recommended. PMID- 22775777 TI - Hepatitis C RNA clearance after treatment with ezetimibe. PMID- 22775778 TI - Investigation of intracellular signalling cascades mediating stimulatory effect of a Gymnema sylvestre extract on insulin secretion from isolated mouse and human islets of Langerhans. AB - AIM: Traditional plant-based remedies such as Gymnema sylvestre (GS) extracts have been used to treat diabetes mellitus for many centuries. We have shown previously that a novel GS extract, OSA(r), has a direct effect on insulin secretion but its mode of action has not been studied in detail Thus this study investigated the possible underlying mechanism(s) by which OSA(r) exerts its action. METHODS: The effects of OSA(r) on [Ca(2+)]i and K(+) conductances were assessed by Ca(2+) microfluorimetry and electrophysiology in dispersed mouse islets and MIN6 beta-cells, respectively. Isolated mouse (from 20 to 25 mice) and human (from 3 donors) islets, and MIN6 beta-cells, were used to investigate whether the stimulatory effect of OSA(r) on insulin secretion was dependent on the presence of extracellular calcium and protein kinase activation. RESULTS: OSA (r)-induced insulin secretion from mouse islets and MIN6 beta-cells was inhibited by nifedipine, a voltage-gated Ca(2+) channel blocker, and by the removal of extracellular Ca(2+), respectively. OSA(r) did not affect the activities of KATP channels or voltage-dependent K(+) channels in MIN6 beta-cells but it caused an increase in intracellular Ca(2+) ([Ca(2+)]i) concentrations in Fura-2-loaded mouse islet cells. The insulin secretagogue effect of OSA(r) was dependent, in part, on protein kinase activation since incubating mouse or human islets with staurosporine, a general protein kinase inhibitor, resulted in partial inhibition of OSA(r)-induced insulin secretion. Experiments using permeabilized, Ca(2+) clamped MIN6 beta-cells revealed a Ca(2+)-independent component action of OSA(r) at a late stage in the stimulus-response coupling pathway. OSA(r)-induced insulin secretion was unexpectedly associated with a decrease in intracellular cAMP levels. CONCLUSIONS: These data indicate that the GS isolate OSA(r) stimulates insulin secretion from mouse and human islets in vitro, at least in part as a consequence of Ca(2+) influx and protein kinase activation. PMID- 22775779 TI - Post-hatching parental care masks the effects of egg size on offspring fitness: a removal experiment on burying beetles. AB - Parents can increase the fitness of their offspring by allocating nutrients to eggs and/or providing care for eggs and offspring. Although we have a good understanding of the adaptive significance of both egg size and parental care, remarkably little is known about the co-evolution of these two mechanisms for increasing offspring fitness. Here, we report a parental removal experiment on the burying beetle Nicrophorus vespilloides in which we test whether post hatching parental care masks the effect of egg size on offspring fitness. As predicted, we found that the parent's presence or absence had a strong main effect on larval body mass, whereas there was no detectable effect of egg size. Furthermore, egg size had a strong and positive effect on offspring body mass in the parent's absence, whereas it had no effect on offspring body mass in the parent's presence. These results support the suggestion that the stronger effect of post-hatching parental care on offspring growth masks the weaker effect of egg size. We found no correlation between the number and size of eggs. However, there was a negative correlation between larval body mass and brood size in the parent's presence, but not in its absence. These findings suggest that the trade off between number and size of offspring is shifted from the egg stage towards the end of the parental care period and that post-hatching parental care somehow moderates this trade-off. PMID- 22775780 TI - Comparing a script concordance examination to a multiple-choice examination on a core internal medicine clerkship. AB - BACKGROUND: Script concordance (SC) questions, in which a learner is given a brief clinical scenario then asked if additional information makes one hypothesis more or less likely, with answers compared to a panel of experts, are designed to reflect a learner's clinical reasoning. PURPOSE: The purpose is to compare reliability, validity, and learner satisfaction between a three-option modified SC examination to a multiple-choice question (MCQ) examination among medical students during a 3rd-year internal medicine clerkship, to compare reliability and learner satisfaction of SC between medical students and a convenience sample of house staff, and to compare learner satisfaction with SC between 1st- and 4th quarter medical students. METHODS: Using a prospective cohort design, we compared the reliability of 20-item SC and MCQ examinations, sequentially administered on the same day. To measure validity, scores were compared to scores on the National Board of Medical Examiners (NBME) subject examination in medicine and to a clinical performance measure. SC and MCQ were also administered to a convenience sample of internal medicine house staff. Medical student and house staff were anonymously surveyed regarding satisfaction with the examinations. RESULTS: There were 163 students who completed the examinations. With students, the initial reliability of the SC was half that of MCQ (KR20 0.19 vs. 0.41), but with house staff (n = 15), reliability was the same (KR20 = 0.52 for both examinations). SC performance correlated with student clinical performance, whereas MCQ did not (r = .22, p = .005 vs. .11, p = .159). Students reported that SC questions were no more difficult and were answered more quickly than MCQ questions. Both exams were considered easier than NBME, and all 3 were considered equally fair. More students preferred MCQ over SC (55.8% vs. 18.0%), whereas house staff preferred SC (46% vs. 23%; p = .03). CONCLUSIONS: This SC examination was feasible and was more valid than the MCQ examination because of better correlation with clinical performance, despite being initially less reliable and less preferred by students. SC was more reliable and preferred when administered to house staff. PMID- 22775781 TI - The impact of two clinical shift allocation models on student experiences in an emergency medicine clerkship. AB - BACKGROUND: Medical students on Emergency Medicine (EM) clerkships are traditionally assigned work shifts in a manner that provides a mix of daytime, evening, overnight, and weekend shifts. Whether or not this shift allocation model provides the optimal educational experience remains unclear. PURPOSE: The purpose of this study was to compare the impact of two different shift allocation models on the student's clerkship experience. Specifically, we set out to compare the traditional shift allocation model to a novel model designed to maximize teacher-learner continuity. METHODS: This was a prospective, crossover, cohort study of medical students participating in an EM clerkship at one institution from January 1 through April 31, 2010. All students completed 2 weeks of shifts under the "traditional shift model" and 2 weeks of shifts under the "continuity based shift model." In the latter, the guiding principle of student shift allocation was continuity between teacher and learner. Students completed coded surveys after each 2-week block that were later matched and analyzed using 2-way ANOVAs with 1 repeated measure. In addition, all students participated in a semistructured group interview at the completion of both blocks. The interviews were recorded, transcribed, and analyzed using qualitative methods. Themes and subthemes that emerged were assessed for frequency of occurrence. RESULTS: Eighteen medical students consented to participate. Students rated the continuity based shift model higher on all 10 survey items. However, only the items that asked specifically about "faculty"-faculty teaching, faculty interaction, frequency and quality of faculty feedback-were rated significantly higher when students worked under the continuity-based shift model. Qualitative analysis of group interviews revealed 6 major themes and 16 subthemes. Students described feedback (N = 16/117) and the teacher-learner relationship (N = 21/117) as superior under the continuity-based shift model. CONCLUSIONS: Changes in shift allocation affects student experience in an EM clerkship. A shift allocation model that maximizes the continuity between teacher and learner is perceived by students to improve feedback and the teacher-learner relationship. PMID- 22775782 TI - A replicable model of a health literacy curriculum for a third-year clerkship. AB - Contrary to recommendations from national medical organizations, medical school education often fails to train students to interact effectively with patients with limited health literacy. The objectives of a new health literacy curriculum in a family medicine clerkship were to increase students' knowledge of health literacy and develop comfort with specific communication skills. Instructional strategies included lectures, practice with standardized patients (SPs), and a facilitated discussion board. At the end of the first year of the curriculum, there was a statistically significant increase in students' knowledge of health literacy. During the final testing with SPs, students achieved high scores for health literacy related communication skills. The curriculum is replicable at other universities and was an effective and efficient way for medical students to learn about health literacy and to acquire valuable skills to improve their patients' understanding of health information. PMID- 22775783 TI - Medical students hierarchy of values and sense of responsibility. AB - BACKGROUND: Ethical skills and personal values contribute to making students competent and humane physicians. However, there is not much research done on medical students' personal values and sense of responsibility. PURPOSES: The study was designed to examine differences in personal values and sense of responsibility between medical students and their peers. METHODS: The students performed demographic survey and reliable tests: Scheler's Value Scale and Responsibility Scale. RESULTS: Medical students scored higher in responsibility, also in values of hedonism and truth, and scored lower in values of holy, both religion and secularism. They did not differ from the control group in values of vitality, aesthetics, morals, physical fitness as well as strength and stamina. CONCLUSION: Medical students differ from their peers from other faculties at the level of responsibility and hierarchy of values. They rate higher at such values as hedonism and truth and lower values of holy. PMID- 22775784 TI - A low-cost method for performing a curriculum gap-analysis in developing countries: medical school competencies in Ghana. AB - BACKGROUND: In this study, we undertook a comparison of the international, national, and local curricula of Ghanaian medical schools in order to identify any gaps. PURPOSE: To identify gaps in the Ghanaian medical school curriculum. METHODS: The Ministry of Health and the two major sites for medical education in Ghana (UGMS, KNUST) participated using the only internationally accepted and validated set of outcome standards for medical education, the Global Minimum Essential Requirements. The competencies were reviewed by two U.S. consultants (DS, SR) and then edited, revised, and validated by individuals who are deeply involved in medical education in Ghana. RESULTS: The KNUST team validated 6 gaps in their curriculum, and the team from UGMS identified 5. The standards were found by the U.S.-based consultants and validated by the Ghanaian team to have 6 gaps, many of which overlapped with those found in the Ghanaian medical school curricula. CONCLUSIONS: This analysis is a first step to determining physician training competency and an inexpensive method for identifying agreed-upon gaps in the current national requirements and local curriculum. PMID- 22775785 TI - Opportunities and challenges in integrating electronic health records into undergraduate medical education: a national survey of clerkship directors. AB - BACKGROUND: Few studies have reported on the utilization and the effect of electronic health records on the education of medical students. PURPOSE: The purpose of this study was to describe the current use of electronic health records by medical students in the United States and explore the opportunities and challenges of integrating electronic health records into daily teaching of medical students. METHODS: A survey with 24 questions regarding the use of electronic health records by medical students was developed by the Alliance for Clinical Educators and sent to clerkship directors across the United States. Both quantitative and qualitative responses were collected and analyzed to determine current access to and use of electronic health records by medical students. RESULTS: This study found that an estimated 64% of programs currently allow student use of electronic health records, of which only two thirds allowed students to write notes within the electronic record. Overall, clerkship directors' opinions on the effects of electronic health records on medical student education were neutral, and despite acknowledging many advantages to electronic health records, there were many concerns raised regarding their use in education. CONCLUSIONS: Medical students are using electronic health records at higher rates than physicians in practice. Although this is overall reassuring, educators have to be cautious about the limitations being placed on student's documentation in electronic health records as this can potentially have consequences on their training, and they need to explore ways to maximize the benefits of electronic health records in medical education. PMID- 22775786 TI - Assessing physician leadership styles: application of the situational leadership model to transitions in patient acuity. AB - BACKGROUND: The situational leadership model suggests that an effective leader adapts leadership style depending on the followers' level of competency. PURPOSE: We assessed the applicability and reliability of the situational leadership model when observing residents in simulated hospital floor-based scenarios. METHODS: Resident teams engaged in clinical simulated scenarios. Video recordings were divided into clips based on Emergency Severity Index v4 acuity scores. Situational leadership styles were identified in clips by two physicians. Interrater reliability was determined through descriptive statistical data analysis. RESULTS: There were 114 participants recorded in 20 sessions, and 109 clips were reviewed and scored. There was a high level of interrater reliability (weighted kappa r = .81) supporting situational leadership model's applicability to medical teams. A suggestive correlation was found between frequency of changes in leadership style and the ability to effectively lead a medical team. CONCLUSIONS: The situational leadership model represents a unique tool to assess medical leadership performance in the context of acuity changes. PMID- 22775787 TI - Implementing faculty evaluation of written sign-out. AB - PURPOSE: Recently the Accreditation Council for Graduate Medical Education mandated decreased shift duration for intern physicians to no more than 16 hours. Such work-hour restrictions are likely to increase patient care hand-offs. It is well accepted that sign-out (i.e., hand-off) processes are error prone and lack standardization. Moreover, many residency programs do not evaluate sign-out. We designed and tested whether a sign-out evaluation process could be implemented to improve written sign-out. METHOD: Based on observed sign-out deficiencies at our institution we adapted a simple curriculum incorporating the SIGNOUT mnemonic, which we paired with weekly faculty member evaluation and feedback on sign-out using a structured sign-out evaluation tool. Later in the week, written sign-out was independently scored by 2-blinded senior resident reviewers who compared the inclusion of sign-out content, organization, and readability. RESULTS: Compared to baseline data in 128 written sign-outs, the pairing of a 1-page curriculum with weekly faculty member evaluation of written sign-out improved the inclusion of advanced directives from 38% to 69% (p < .001) and anticipatory guidance from a mean score of 1.8 (SD = 1.2) to 2.3 (SD = 1.5) on a 5-point scale (p = .01) in 177 written sign-outs. Readability and organization were unchanged. CONCLUSIONS: A simple curriculum paired with structured faculty evaluation and feedback can improve some parameters of sign-out. Structured evaluative sign-out tools may be useful to improve and teach sign-out skills. PMID- 22775788 TI - Morning report blog: a web-based tool to enhance case-based learning. AB - BACKGROUND: Morning report is an interactive case-based teaching session common to internal medicine training programs across North America. DESCRIPTION: We report here on a morning report web log ("blog"), created and updated after morning report sessions by the Chief Medical Resident with pertinent clinical topics, links to journal articles, and medical images. Trainees on their internal medicine rotation were e-mailed a web link with each posting. The aim was to enhance learning on clinical topics discussed at morning report by reinforcing topics and promoting further reading. EVALUATION: The educational impact of the blog was evaluated using detailed web metrics and surveys of attendees. The intended audience spent on average more than 5 min reading the blog and viewed more than 3 pages per visit. Almost half of attendees accessed the blog after completing their internal medicine rotation. The blog was also accessed by a global audience. Trainees rated the blogs a useful learning tool and cited it to be among the top 3 educational resources accessed during their rotation. CONCLUSIONS: In summary, a morning report blog was perceived by learners to be an effective complement to case-based teaching sessions. The combination of novel web metrics and survey data allowed for a multifaceted evaluation of the educational impact of the blog. PMID- 22775789 TI - Faculty development as transformation: lessons learned from a process-oriented program. AB - BACKGROUND: Faculty development programs tend to be oriented around content, yet many have produced positive outcomes unrelated to the content. We describe a faculty development program that utilized the processes of shared reading and guided reflection espoused by narrative medicine. DESCRIPTION: To date, 25 preceptors in the Foundations of Clinical Medicine course have participated. The program consists of weekly seminars in which participants actively engage with text as a basis for conversation around content as well as teaching strategies. EVALUATION: Using qualitative methods, we examined notes from seminars, in-depth interviews, and review of curricular documents; we used conceptual frameworks from education as interpretive lenses. Participants recognized both personal growth and transformation in relationships with each other, which created the opportunity, and the means, to address and reshape norms and teaching practices at the institution. CONCLUSIONS: Process-oriented faculty development programs may foster growth of individuals, contribute to transformation in relationships, and ultimately influence teaching practices. PMID- 22775790 TI - An innovative process for faculty development in residency training. AB - BACKGROUND: For programs to accomplish the goals of the Accreditation Council of Graduate Medical Education (ACGME) Outcome Project, faculty must be trained to deliver and assess education that is level-specific, competency-based, standardized, integrated, and easily accessible. DESCRIPTION: An innovative faculty development model that accomplishes these goals is described. This model trained faculty to analyze curricular needs and then to design, disseminate, and evaluate their curricula. This model utilized guided experiential learning that promoted the creation of residency program curricula and faculty buy-in. EVALUATION: Key outcomes included high levels of resident satisfaction and use of the curricula, improved tracking of rotation progress, improved faculty satisfaction with their role as educators, perceived improvement in resident evaluations, and increased involvement of faculty in creating and teaching to the curriculum. CONCLUSION: This process may be adapted by other programs based on their available resources to address faculty development needs. The process serves as a model for meeting ACGME requirements. PMID- 22775791 TI - Medical student documentation in electronic health records: a collaborative statement from the Alliance for Clinical Education. AB - PURPOSE: The electronic health record (EHR) is an important advancement in health care. It facilitates improvement of health care delivery and coordination of care, but it creates special challenges for student education. This article represents a collaborative effort of the Alliance for Clinical Education (ACE), a multidisciplinary group formed in 1992. ACE recognizes the importance of medical student participation in patient care including the ability of documentation. This article proposes guidelines that can be used by educators to establish expectations on medical student documentation in EHRs. SUMMARY: To provide the best education for medical students in the electronic era, ACE proposes to use the following as practice guidelines for medical student documentation in the EHR: (a) Students must document in the patient's chart and their notes should be reviewed for content and format, (b) students must have the opportunity to practice order entry in an EHR--in actual or simulated patient cases--prior to graduation, (c) students should be exposed to the utilization of the decision aids that typically accompany EHRs, and (d) schools must develop a set of medical student competencies related to charting in the EHR and state how they would evaluate it. This should include specific competencies to be documented at each stage, and by time of graduation. In addition, ACE recommends that accreditation bodies such as the Liaison Committee for Medical Education utilize stronger language in their educational directives standards to ensure compliance with educational principles. This will guarantee that the necessary training and resources are available to ensure that medical students have the fundamental skills for lifelong clinical practice. CONCLUSIONS: ACE recommends that medical schools develop a clear set of competencies related to student in the EHR which medical students must achieve prior to graduation in order to ensure they are ready for clinical practice. PMID- 22775792 TI - Obesity educational interventions in U.S. medical schools: a systematic review and identified gaps. AB - BACKGROUND: Obesity is the second leading cause of preventable death in the United States. However, physicians feel poorly trained to address the obesity epidemic. This article examines effective training methods for overweight and obesity intervention in undergraduate medical education. Using indexing terms related to overweight, obesity, and medical student education, we conducted a literature searched PubMed PsycINFO, Cochrane, and ERIC for relevant articles in English. References from articles identified were also reviewed to located additional articles. SUMMARY: We included all studies that incorporated process or outcome evaluations of obesity educational interventions for U.S. medical students. Of an initial 168 citations, 40 abstracts were retrieved; 11 studies were found to be pertinent to medical student obesity education, but only 5 included intervention and evaluation elements. Quality criteria for inclusion consisted of explicit evaluation of the educational methods used. Data extraction identified participants (e.g., year of medical students), interventions, evaluations, and results. These 5 studies successfully used a variety of teaching methods including hands on training, didactic lectures, role-playing, and standardized patient interaction to increase medical students' knowledge, attitudes, and skills regarding overweight and obesity intervention. Two studies addressed medical student bias toward overweight and obese patients. No studies addressed health disparities in the epidemiology and bias of obesity. CONCLUSIONS: Despite the commonly cited "obesity epidemic," there are very few published studies that report the effectiveness of medical school obesity educational programs. Gaps still exist within undergraduate medical education including specific training that addresses obesity and long-term studies showing that such training is retained. PMID- 22775797 TI - Microbialite genetic diversity and composition relate to environmental variables. AB - Microbialites have played an important role in the early history of life on Earth. Their fossilized forms represent the oldest evidence of life on our planet dating back to 3500 Ma. Extant microbialites have been suggested to be highly productive and diverse communities with an evident role in the cycling of major elements, and in contributing to carbonate precipitation. Although their ecological and evolutionary importance has been recognized, the study of their genetic diversity is yet scanty. The main goal of this study was to analyse microbial genetic diversity of microbialites living in different types of environments throughout Mexico, including desert ponds, coastal lagoons and a crater-lake. We followed a pyrosequencing approach of hypervariable regions of the 16S rRNA gene. Results showed that microbialite communities were very diverse (H' = 6-7) and showed geographic variation in composition, as well as an environmental effect related to pH and conductivity, which together explained 33% of the genetic variation. All microbialites had similar proportions of major bacterial and archaeal phyla. PMID- 22775798 TI - Simple and highly sensitive measurement method for detection of glass transition temperatures of polymers: application of ESR power saturation phenomenon with conventional spin-probe technique. AB - A combination of the microwave power saturation (MPS) method of electron spin resonance (ESR) and spin probing is proposed as a simple and practical technique for detecting the glass transition temperatures, T(g), of polymers with high sensitivity. Effects of the spin-probe size and concentration on the T(g) value of polystyrene (PS) determined by MPS, T(g,ESR), were first evaluated. Spin probed PS with four types of nitroxides, namely, di-tert-butyl nitroxide (DBN), 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), 4-benzoyloxy-2,2,6,6 tetramethylpiperidine-1-oxyl (BZONO), and 4',4'-dimethyl-spiro(5alpha-cholestane 3,2'-oxazolidin)-3'-yloxy free radical (CHOL), having molecular weights of 144, 156, 276, and 473, respectively, and spin-labeled PS with TEMPO were prepared. The T(g,ESR) values for the spin-probed PS with DBN, TEMPO, BZONO, and CHOL and spin-labeled PS were determined to 360, 363, 374, 374, and 375 K, respectively, within experimental uncertainties of 2 K, whereas the glass transition temperature determined by DSC, T(g,DSC), was 375 K for all samples. A significant decrease in T(g,ESR) for small spin probes was shown to be due to decoupling between the mobilities of small spin probes and PS segments. Concerning the concentration, a decrease in the saturation factor, S, induced by shortening of the spin-spin relaxation time was observed for the spin-probed PS with CHOL when the concentration of CHOL was more than 1.0 wt %. Furthermore, T(g,ESR) decreased slightly with increasing weight fraction of CHOL because of the "plasticizer effect" of CHOL. However, the T(g,ESR) and T(g,DSC) values corresponded for each concentration. Thus, large spin probes, such as CHOL and BZONO, are appropriate for the determination of T(g,ESR) values; the concentration of the spin probes does not affect the T(g,ESR) value unless the overall T(g) value is reduced by blending of excess spin probes. Finally, measurements of T(g,ESR) in PS/silica composites containing more than 95 wt % silica are shown as an application example of the present method. T(g,ESR) was clearly determined even for the PS/silica composites with 98 wt % silica; a decrease in T(g,ESR) with increasing silica content was observed. PMID- 22775800 TI - On simulation and analysis of variable-rate pumping tests. AB - Analytical solutions for constant-rate pumping tests are widely used to infer aquifer properties. In this note, we implement a methodology that approximates the time-varying pumping record as a series of segments with linearly varying pumping rates. We validate our approach using an analytical solution for a sinusoidally varying pumping test. We also apply our methodology to analyze synthetic test data and compare the results with those from a commonly used method where rate variations are represented by a series of constant-rate steps. PMID- 22775799 TI - A cross-over study of effects on the hypothalamus-pituitary-adrenal (HPA) axis and the sympathoadrenergic system in magnetic field strength exposure from 0 to 7 T. AB - The concept of stress is relevant to magnetic resonance imaging (MRI) examination in various ways. First, levels of stress to staff and patients have not been quantified in ultra-high magnetic fields. Second, research is increasingly interested in experimentally defining regional brain activity during stress. It is therefore important to know whether exposure to the ultra-high static magnetic fields per se might also lead to neurohormonal responses in the hypothalamus pituitary-adrenal axis and the sympathoadrenal systems. In the present blinded case cross-over study with 41 healthy participants, we measured cortisol not only before and after but also during static magnetic field exposure in MRI scanners. Measures of catecholamines before and after exposure were also part of the study protocol. Using three different field strengths (1.5, 3 and 7 T) and a mock scanner (0 T), we examined whether not only the MRI procedure but also the static magnetic field per se has an influence on the neuroendocrine responses. We found no significant differences in the course of cortisol or catecholamine concentrations between the different static magnetic fields. Our study suggests that the results of MRI studies using stress-paradigms are not influenced by the static magnetic field itself. PMID- 22775801 TI - Primary cutaneous anaplastic large-cell lymphoma occurring in a case of chronic myeloid leukemia in remission. PMID- 22775966 TI - Haemorrhoids are associated with erectile dysfunction: a population-based study. AB - Haemorrhoids are associated with regional vascular abnormalities and rectal pain, which are hypothesized to increase the risk of erectile dysfunction (ED); however, few studies have investigated the association between ED and haemorrhoids. This case-control study aimed to estimate the association between haemorrhoids and ED by using a population-based data in Taiwan. We identified 6,310 patients with ED as cases and randomly selected 31,550 controls. Conditional logistic regression was performed to compute the odds ratio (OR) for having been previously diagnosed with haemorrhoids between cases and controls. The results show that haemorrhoids were found to be present among 1,572 (24.9%) cases and 4,491 (14.20%) controls. The OR for prior haemorrhoids among cases was 1.90 (95% CI = 1.78-2.03) when compared with controls after adjusting for monthly income, geographical location, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity and alcohol abuse/alcohol dependence syndrome. Younger cases demonstrated a higher risk for prior haemorrhoids when compared with controls. In particular, the adjusted OR among cases <30 years old was 3.71 (95% CI = 2.74-5.02) when compared with controls. We concluded that there was an association between ED and a prior diagnosis of haemorrhoids. PMID- 22775967 TI - Colloidal centrifugation of stallion semen results in a reduced rate of sperm DNA fragmentation. AB - Stallion spermatozoa recovered and examined immediately after colloidal centrifugation resulted in a higher straight-line velocity (VSL) than sperm processed using direct conventional centrifugation (p = 0.000), but there was no differences in the progressive motility or sperm DNA fragmentation (SDF) as determined by the sperm chromatin dispersion assay. However, when centrifuged spermatozoa were incubated at 37 degrees C for 24 h to determine the rate of SDF (r-SDF), a lower r-SDF (p = 0.0011) was observed in those sperm recovered after colloidal separation (0.5 +/- 0.1%/h) compared to direct (1.2 +/- 0.4%/h) or no centrifugation (r-SDF = 1.2 +/- 0.3%/h). These results confirm that colloidal separation of stallion spermatozoa results in prolonged sperm DNA longevity, but these differences were only apparent following a period of incubation and dynamic assessment. Consequently, we strongly recommend the use of the dynamic form of the SDF assay for evaluating centrifugation and/or other ex vivo procedures, as a single basal assessment of SDF may inadvertently result in a false-positive evaluation of DNA quality. PMID- 22775968 TI - Behaviour of soft tissues healing around single bone-level-implants placed immediately after tooth extraction A 1 year prospective cohort study. AB - AIM: The aim of this study was to verify if the three-dimensional implant position in fresh alveolar socket may influence the maintenance of stable gingival margins around single premolar restorations with immediate implant placement. METHODS: After 16 weeks of healing, implants were loaded with single crowns. Documentation consisted in peri-apical radiographs taken: before treatment; at the time of implant placement; at the time of prosthetic rehabilitation and 12 months after the start of prosthetic function. Parameters assessed were: the presence/absence of inter-proximal papilla; the inter-implant tooth distance (ITD); the distance from the base of the crown contact-point to the inter-dental bone crest (CPB); and the buccal-gingival tissue modifications. ITD, CPB values and the modification of buccal-gingival tissue were determined using an image processing software. RESULTS: Twenty-one healthy patients with thick gingival biotype, with a total of 21 maxillary premolars scheduled for extractions were enrolled. Following extraction, implants were immediately positioned. A 100% of implant survival rate was observed after 12 months of function. The presence of the mesial papilla was significantly correlated with the mean mesial CPB value (P = 0.0519 by means of two-tailed Mann-Whitney U test). No significant correlation was found between the mesial papilla presence and the mean mesial ITD score (P = 0.7722 by means of two-tailed Mann-Whitney U test). Furthermore, the presence of the distal papilla was not significantly correlated with the mean distal ITD and CPB values: scores of 0.7195 and 0.8225 were calculated respectively. CONCLUSION: In the premolar area, the relationship between the presence of a complete inter-proximal papilla and ITD parameter was not significant (P > 0.05). The relationship between the presence of a complete inter-proximal papilla and CPB parameter still remain unclear. Nevertheless, a more large sample size is required to confirm this trend. Moreover, it was observed that the buccal-gingival tissue withdrew in the range 0-1 mm after 1 year of prosthetic function. PMID- 22775969 TI - Exploring reflection as a process embedded in experienced nurses' practice: a qualitative study. AB - AIM: This article is a report of a study aimed at obtaining an in-depth description of how experienced acute care staff nurses perceive and use reflection in clinical practice. BACKGROUND: Reflection is viewed as a critical component of professional practice. The basic assumption is that reflection involves a deliberate process of thinking about a clinical situation which leads to insight and a subsequent change in practice. Several prescriptive models for reflection exist to provide a guide for reflection, however, few are grounded from an empirical examination of reflection in practice. There is a dearth of empirical data on what is actually happening in practice. DESIGN: Descriptive, qualitative. METHODS: In-depth interviews with 12 experienced acute care staff nurses in a community hospital in Northeastern USA was used to address the study aims. Data were collected between November 2009-May 2010. RESULTS/FINDINGS: Examples of reflection were embedded in patient situations needing immediate nursing intervention. Reflection was a process involving four phases: Framing of the Situation, Pausing, Engaging in Reflection, and Emerging Intentions. CONCLUSION: Experienced nurses used a process of reflection-on-action in practice. They gained insight and formulated intentions for change in nursing practice. Structured facilitated reflection might assist nurses in achieving a depth of reflection necessary to move from their intentions to changes in practice. PMID- 22775970 TI - Sirolimus use and incidence of venous thromboembolism in cardiac transplant recipients. AB - Sirolimus is an immunosuppressive agent increasingly used in cardiac transplant recipients in the setting of allograft vasculopathy or worsening renal function. Recently, sirolimus has been associated with increased risk of venous thromboembolism (VTE) in lung transplant recipients. To investigate whether this association is also present in cardiac transplant recipients, we retrospectively reviewed the charts of 67 cardiac transplant recipients whose immunosuppressive regimen included sirolimus and 134 matched cardiac transplant recipients whose regimen did not include sirolimus. Rates of VTE were compared. Multivariable Cox proportional hazards models tested the association of sirolimus use with VTE. A higher incidence of VTE was seen in patients treated with vs. without sirolimus (8/67 [12%] vs. 9/134 [7%], log-rank statistic: 4.66, p=0.03). Lower body mass index (BMI) and total cholesterol levels were also associated with VTE (p<0.05). The association of sirolimus with VTE persisted when adjusting for BMI (hazard ratio [95% confidence interval]: 2.96 [1.13, 7.75], p=0.03) but not when adjusting for total cholesterol (p=0.08). These data suggest that sirolimus is associated with an increased risk of VTE in cardiac transplant recipients, a risk possibly mediated through comorbid conditions. Larger, more conclusive studies are needed. Until such studies are completed, a heightened level of awareness for VTE in cardiac transplant recipients treated with sirolimus appears warranted. PMID- 22775971 TI - Reassessing specimen number and diagnostic yield of ultrasound guided breast core biopsy. AB - To reassess the minimum number of specimens required for an accurate diagnosis compared to the standard acquisition of five specimens. A total of 190 consecutive breast mass biopsies were performed using a 14-gauge core biopsy needle under ultrasound guidance. Two to six specimens were obtained from each mass and placed in sequential containers. Each specimen was evaluated by a pathologist in the order it was obtained and was labeled as "diagnostic' or 'non diagnostic'. During the biopsy procedure, the radiologist indicated after which number biopsy he was confident that an adequate diagnostic specimen had been obtained. This was based upon real-time visualization of the needle passing through the lesion and whether the specimen sank or floated in formalin. These observations were compared with the pathologic diagnostic yield according to specimen number. Fifty-eight lesions (30.5%) were malignant, four (2.1%) were atypical, and 128 (67.4%) were benign. Histologic diagnosis was obtained after the first specimen in 157 (82.6%) lesions, the second specimen in 172 (90.5%) lesions, the third specimen in 186 (97.9%) lesions, the fourth specimen in 188 (98.9%) lesions, and the fifth specimen in 190 (100%) lesions. A histologic diagnosis was made in 90% of the malignant lesions after the first biopsy pass, 95% after the second pass, 98% after the third pass, and 100% after the fourth and fifth passes. Nine (4.7%) lesions showed discrepancy between the radiologist's confidence of diagnosis and pathologic diagnostic yield. Of these lesions, seven were benign and two were malignant. A diagnostic yield of 95% was obtained based on operator estimate of the minimum number of required core biopsies. A high diagnostic yield of 98% was achieved after three biopsy passes and 100% after five passes. PMID- 22775972 TI - Sex differences in the renal vascular response to angiotensin II involves the Mas receptor. AB - AIM: The renin-angiotensin system (RAS) depressor arm, particularly renal angiotensin type 2 receptor (AT(2) R) and Mas receptor (masR) expression, is enhanced in females, which may contribute to renal and cardiovascular protection. We examined the hypotheses that masR activation increases renal blood flow (RBF) at rest and attenuates the reduction in RBF in response to angiotensin II (AngII) infusion in female rats. Furthermore, we postulated that combined activation of the AT(2) R and masR would produce a greater response than masR activation alone. METHODS: In anaesthetized male and female Wistar rats, mean arterial pressure (MAP) and RBF responses during graded AngII infusion (30-1000 ng kg(-1) min(-1) i.v.) were assessed following pre-treatment with vehicle, the masR antagonist A779, or A779 plus the AT(2) R antagonist PD123319. RESULTS: Basal MAP was not altered by any pre-treatment. Basal RBF decreased approx. 20% in female (P < 0.05), but not male rats in response to A779. However, basal RBF was not altered by A779 + PD123319. AngII infusion reduced RBF in a dose-related fashion (P(dose) < 0.0001) and masR blockade did not alter the RBF response to AngII infusion in male or female rats. However, A779 + PD123319 attenuated the reduction in RBF response to AngII in females (P(group) < 0.005), but not males. CONCLUSION: The impact of the masR on renal haemodynamics appears to be sexually dimorphic, with greater effects in female than male rats. However, the paradoxical effects of dual AT(2) R and masR blockade suggest that a greater understanding of the complex interactions between RAS components is required before the therapeutic opportunities of AT(2) R and/or masR stimulation can be advanced. PMID- 22775973 TI - Seroprevalence of antibodies against the excreted antigen superoxide dismutase by Trypanosoma cruzi in dogs from the Yucatan Peninsula (Mexico). AB - Numerous studies have shown the role of dogs as a reservoir for the American trypanosomiasis, as the bridge connecting sylvatic and peridomestic cycles. The objective of this study was to determine the prevalence of American trypanosomiasis in the dog population (630 sera) from seven localities in the Yucatan Peninsula (city of Merida and the towns of Molas, Playa del Carmen, Akumal, Xcalacoop, Xcalac and Xahuachol). These data are key for developing control measures for the disease. The sera were analysed to detect antibodies against Trypanosoma cruzi, using Fe-SOD excreted as the antigenic fraction by ELISA and Western blot as confirmation. The total prevalence found in the Yucatan Peninsula was some 14.76%, with 10.74% in the state of Yucatan (city of Merida, towns of Molas and Xcalacoop) and 21.34% in the state of Quintana Roo (towns of Playa del Carmen, Akumal, Xcalac and Xahuachol). However, a more thorough epidemiological study of the dog population, both wild and urban, in the Yucatan Peninsula will be required to design a control strategy for these diseases, paying particular attention to the population affected and even broadening the study to other Mexican states as well as neighbouring countries. These results again confirm that iron-superoxide dismutase excreted by T. cruzi constitutes a good source of antigen for serodiagnosis in epidemiological studies. PMID- 22775974 TI - Detection of a novel HLA-DQB1 allele, designated DQB1*06:49. AB - We report a novel allele HLA-DQB1*06:49 with a G->T transversion, most closely resembling HLA-DQB1*06:02:01. PMID- 22775975 TI - Successful unrelated bone marrow transplantation in two siblings with alpha mannosidosis. AB - Alpha-mannosidosis is a rare lysosomal storage disorder with an autosomal recessive inheritance. Deficient alpha-mannosidase activity leads to lysosomal accumulation of mannose-rich oligosaccharides. The disease characterized by mental retardation, skeletal changes, hearing impairment, and recurrent infections. Stem cell transplantation has been shown to be an effective treatment. It works by providing increased levels of alpha-mannosidase in the localized extracellular milieu to provide improvements in skeletal malformations, neurocognitive, and sensorineural function. In this case report, we describe a pair of siblings with alpha-mannosidosis who successfully underwent HSCT from matched unrelated donors. In both siblings, enzyme levels reached to normal limits and improvements in clinical symptoms were recognized early after HSCT. We conclude that HSCT should be considered as a therapeutic approach in patients with alpha-mannosidosis before disease-related complications have developed. PMID- 22775976 TI - Safety, pharmacokinetics and pharmacodynamics of multiple-ascending doses of the novel glucokinase activator AZD1656 in patients with type 2 diabetes mellitus. AB - AIMS: To assess the safety, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel glucokinase activator AZD1656 in patients with type 2 diabetes mellitus (T2DM). METHODS: This randomized, single-blind, placebo controlled, monotherapy study was carried out in two parts. In part A, 32 patients received AZD1656 (7, 20, 40 or 80 mg) twice daily or placebo for 8 days in hospital. In part B, another 20 patients received, as outpatients, individually titrated AZD1656 15-45 mg twice daily or placebo for 28 days. Safety, pharmacokinetics and pharmacodynamic variables were evaluated. RESULTS: AZD1656 was generally well tolerated. Pharmacokinetics of AZD1656 were virtually dose- and time-independent. AZD1656 was rapidly absorbed and eliminated. An active metabolite was formed which had a longer half-life than AZD1656, but showed ~15% of the area under the plasma concentration versus time curve from 0 to 24 h compared with that of AZD1656. Renal excretion of AZD1656 and the metabolite was low. In part A, fasting plasma glucose (FPG) was reduced by up to 21% and mean 24-h plasma glucose was reduced by up to 24% with AZD1656 versus placebo, depending on dose. No dose-related changes in serum insulin or C-peptide were observed with AZD1656 at the end of treatment. Results in part B confirmed the glucose-lowering effect of AZD1656 versus placebo. CONCLUSIONS: AZD1656 was well tolerated with predictable pharmacokinetics in patients with T2DM. Dose dependent reductions in plasma glucose were observed. PMID- 22775978 TI - Effects of G250 promoter controlled conditionally replicative adenovirus expressing Ki67-siRNA on renal cancer cell. AB - Replication-competent adenovirus (RCAd) has been used extensively in cancer gene therapy, and tumor-selection is critical for the use of replication-competent adenovirus. Here we investigated the anti-tumor characterization of oncolytic virus, whose E1A gene is under the control of a renal cell carcinoma specific promoter - the G250 promoter. The constructed oncolytic virus G250-Ki67 is armed with transgene of Ki67-siRNA, and G250-ZD55-Ki67 also with E1B-55 KD deleted. The tumor-specific expression of E1A and Ki67 was demonstrated by Western blot and immunohistochemistry staining, and the tumor-specific cytotoxicity was assessed by crystal violet staining and cell viability assays. The G250-Ki67 and G250-ZD55 Ki67 adenoviruses could express E1A protein in 786-O and OSRC cell lines but not in ACHN and HK-2 cell lines. The expression of Ki67 gene in 786-O and OSRC cell lines were suppressed by these adenoviruses. The cytotoxic effects induced by G250-ZD55-Ki67 and G250-Ki67 were more obvious on the 786-O cell lines than on the OSRC cell lines. Each group of adenoviruses could inhibit the proliferation of the 786-O cells and OSRC cells. However, the effects induced by G250-ZD55-Ki67 and G250-Ki67 on 786-O cells were stronger than on OSRC cells. Moreover, G250 ZD55-Ki67 had enhanced antitumor activities in these renal cancer cells compared with G250-Ki67. G250 promoter-derived CRAds carrying Ki67-siRNA could highly amplify and express Ki67-siRNA in renal cancer cells with expression of G250 antigen, inhibit renal cancer cells proliferation and induce apoptosis. These results demonstrated that the G250-specific oncolytic adenovirus expressing Ki67 siRNA is applicable for human renal clear cell cancer therapy. PMID- 22775977 TI - Omega-3 fatty acids status in human subjects estimated using a food frequency questionnaire and plasma phospholipids levels. AB - BACKGROUND: Intakes of omega-3 (n-3) fatty acids (FA) are associated with several health benefits. The aim of this study was to verify whether intakes of n-3 FA estimated from a food frequency questionnaire (FFQ) correlate with n-3 FA levels measured in plasma phospholipids (PL). METHODS: The study sample consisted of 200 French-Canadians men and women aged between 18 to 55 years. Dietary data were collected using a validated FFQ. Fasting blood samples were collected and the plasma PL FA profile was measured by gas chromatography. RESULTS: Low intakes of n-3 long-chain FA together with low percentages of n-3 long-chain FA in plasma PL were found in French-Canadian population. Daily intakes of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) were similar between men and women. Yet, alpha-linolenic acid (ALA) and total n-3 FA intakes were significantly higher in men compared to women (ALA: 2.28 g and 1.69 g, p < 0.0001, total n-3 FA: 2.57 g and 1.99 g, p < 0.0001; respectively). In plasma PL, DPA and DHA percentages were significantly different between men and women (DPA: 1.03% and 0.88%, p < 0.0001, DHA: 3.00% and 3.43%, p = 0.0005; respectively). Moreover, DHA (men: r = 0.52, p < 0.0001; women: r = 0.57, p < 0.0001) and total n-3 FA (men: r = 0.47, p < 0.0001; women: r = 0.52, p < 0.0001) intakes were positively correlated to their respective plasma PL FA levels. In women, EPA (r = 0.44, p < 0.0001) and DPA (r = 0.23, p = 0.02) intakes were also correlated respectively with EPA and DPA plasma PL FA percentages. CONCLUSION: Estimated n-3 long-chain FA intake among this young and well-educated French-Canadian population is lower than the recommendations. Further, FFQ data is comparable to plasma PL results to estimate DHA and total n-3 FA status in healthy individuals as well as to evaluate the EPA and DPA status in women. Overall, this FFQ could be used as a simple, low-cost tool in future studies to rank n-3 FA status of individuals. PMID- 22775979 TI - Group therapist as social scientist, with special reference to the psychodynamically oriented psychotherapist. AB - The recent literature suggests a lowering of tensions between psychotherapy practitioners and researchers in the decades-long "psychotherapy war." The author analyzes reasons for the thawing and suggests that the time is ripe for clinicians to assume greater authority in the work of developing models of the psychotherapy change process. The article highlights the unique positioning of the psychodynamic group psychotherapist for advancing this work. PMID- 22775980 TI - Ammonia-oxidizing archaea and nitrite-oxidizing nitrospiras in the biofilter of a shrimp recirculating aquaculture system. AB - This study analysed the nitrifier community in the biofilter of a zero discharge, recirculating aquaculture system (RAS) for the production of marine shrimp in a low density (low ammonium production) system. The ammonia-oxidizing populations were examined by targeting 16S rRNA and amoA genes of ammonia-oxidizing bacteria (AOB) and archaea (AOA). The nitrite-oxidizing bacteria (NOB) were investigated by targeting the 16S rRNA gene. Archaeal amoA genes were more abundant in all compartments of the RAS than bacterial amoA genes. Analysis of bacterial and archaeal amoA gene sequences revealed that most ammonia oxidizers were related to Nitrosomonas marina and Nitrosopumilus maritimus. The NOB detected were related to Nitrospira marina and Nitrospira moscoviensis, and Nitrospira marina-type NOB were more abundant than N. moscoviensis-type NOB. Water quality and biofilm attachment media played a role in the competitiveness of AOA over AOB and Nitrospira marina-over N. moscoviensis-type NOB. PMID- 22775981 TI - Treatment of Haemophilus bacteremia with benzylpenicillin is associated with increased (30-day) mortality. AB - BACKGROUND: Optimal antibiotic treatment strategies of Haemophilus infections are still needed. Therefore, 30-day case fatality rate (CFR) of Haemophilus bacteremia and efficacy of various antibiotic treatment regimes were studied. METHODS: All episodes of Haemophilus bacteremia in the former Copenhagen County during the period 2000-9 were included in the study. Clinical and biochemical findings and outcome were collected retrospectively from medical records. RESULTS: 105 consecutive episodes were identified (median age: 69 years, with only 4 children <16 years), 72% were due to non-typeable -, 16% to typeable H. influenzae, and 11% to other Haemophilus species. Pneumonia was the most common primary focus (in 48%), and 58% of the patients had Charlson comorbidity index > 1. Definitive antibiotic therapy was in 26 cases benzylpenicillin, in 12 cases aminopenicillins, in 50 cases cefuroxime and in 16 cases broadspectrum antibiotics, whereas 1 palliative case died without start of therapy. Whereas the use of broadspectrum antibiotics was related to the severity of the disease (admittance to ICU, need for assisted ventilation or hemodialysis, septic shock), no significant difference in clinical features was demonstrated for therapy with benzylpenicillin, aminopenicillin or cefuroxime, except benzylpenicillin was rarely administered to immunosuppressed patients. The CFR was 22% (23/105). The choice of empiric antibiotic therapy was not significantly associated with mortality (adequate vs. inadequate treatment: 23% (21/93) vs. 17% (2/12), respectively, P > 0.05). In contrast, definite antibiotic therapy with cefuroxime or aminopenicillins resulted in a significantly lower CFR than treatment with benzylpenicillin (12% (6/50) or 0% (0/12) vs. 39% (10/26), respectively, Log rank test P < 0.02). When adjustments were made for other identified risk factors in bivariate logistic regression analysis, treatment with cefuroxime was still were found to be associated with a significantly lower CFR than for benzylpenicillin: OR: 0.21 (0.06-0.69), P = 0.01 (hospital-acquired bacteremia), OR: 0.27 (0.08 0.91), P = 0.04 (polymicrobial episodes), OR: 0.16 (0.04-0.59), P = 0.006 (admittance at intensive care unit), OR: 0.22 (0.06-0.82), P = 0.02 (alcohol abuse), OR: 0.15 (0.04-0.60), P = 0.008 (altered mental state), OR: 0.22 (0.07 0.71), P = 0.01 (temperature < 38 degrees C), OR: 0.23 (0.07-0.79), P = 0.02 (septic shock), OR: 0.21 (0.06-0.69), P = 0.01 (mechanical ventilation). CONCLUSION: Our results suggest that, after susceptibility testing, cefuroxime or aminopenicillins are preferable to benzylpenicillins as definitive therapy for Haemophilus bacteremia. PMID- 22775982 TI - Using virtual reality driving simulators in persons with spinal cord injury: three screen display versus head mounted display. AB - PURPOSE: Virtual reality (VR) is a relatively new technology that is currently utilized in a wide variety of settings to test and train individuals in specialized skills. This study examines methods for improving driver retraining protocols for persons with spinal cord injury (SCI). METHOD: We compared a VR driving simulator, under two different display conditions, a head mounted display (HMD) and a three screen display (TSD) to identify the best method for retraining driving skills following SCI. RESULTS: Although there was minimal evidence for driving performance difficulties in the HMD condition relative to the TSD condition (e.g. greater number of times for being off course and longer stopping latencies for the HMD condition), rates of simulator sickness did not differ between display conditions. CONCLUSIONS: Taken together, findings suggest that both the HMD and the TSD are reasonable simulator options for driver retraining in SCI. PMID- 22775983 TI - Sudden generalized lung atelectasis during thoracotomy following thoracic lavage in 3 dogs. AB - OBJECTIVE: To describe sudden onset of generalized pulmonary atelectasis following thoracic lavage in 3 dogs. SERIES SUMMARY: Thoracic lavage was performed following ligation of a patent ductus arteriosus in case 1, prior to closure of a large traumatic full thickness wound in the chest wall in case 2, and during investigation of an idiopathic spontaneous pneumothorax in case 3. In each case anesthesia and surgery were uneventful until thoracic lavage was performed, after which sudden generalized pulmonary atelectasis was observed. The atelectasis was visualized and was associated with oxyhemoglobin desaturation, decreased end-tidal carbon dioxide partial pressure (ETCO(2)), and a marked increase in the peak inspiratory pressure (PIP) required to achieve visible lung inflation. Occlusion of the endotracheal tube and cervical trachea was directly eliminated as the cause of atelectasis in cases 1 and 2, and indirectly eliminated in case 3. Improvement in pulmonary function occurred in all cases in response to increased PIP +/- positive end expiratory pressure (PEEP). NEW OR UNIQUE INFORMATION PROVIDED: Generalized atelectasis should be considered a possible complication of thoracic lavage performed during thoracotomy. In the cases presented here, it is suspected that pre-existing reduction in lung volume (due to inadequate ventilation, surgical compression, absorption atelectasis) was exacerbated by the addition of the lavage fluid to the thoracic cavity. This pre existing lung collapse is believed to have resulted in reduction of lung volume and that further reduction below the critical closing volume occurred following instillation of saline into the thorax resulting in the subsequent development of generalized atelectasis. The performance of regular arterial blood gas analyses and different ventilation protocols may have prevented the marked atelectasis that was observed in these cases. PMID- 22775984 TI - A cafeteria diet modifies the response to chronic variable stress in rats. AB - Stress is known to lead to metabolic and behavioral changes. To study the possible relationships between stress and dietary intake, male Sprague-Dawley rats were fed one of three diets for 6 weeks: high carbohydrate (HC), high fat (HF), or "Cafeteria" (CAF) (Standard HC plus a choice of highly palatable cafeteria foods: chocolate, biscuits, and peanut butter). After the first 3 weeks, half of the animals from each group (experimental groups) were stressed daily using a chronic variable stress (CVS) paradigm, while the other half of the animals (control groups) were kept undisturbed. Rats were sacrificed at the end of the 6-week period. The effects of stress and dietary intake on animal adiposity, serum lipids, and corticosterone were analyzed. Results showed that both chronic stress and CAF diet resulted in elevated total cholesterol, increased low-density lipoprotein (LDL), and lower high-density lipoprotein (HDL). In addition, increases in body weight, food intake, and intra-abdominal fat were observed in the CAF group compared with the other dietary groups. In addition, there was a significant interaction between stress and diet on serum corticosterone levels, which manifest as an increase in corticosterone levels in stressed rats relative to non-stressed controls in the HC and HF groups but not in the CAF group. These results show that a highly palatable diet, offering a choice of food items, is associated with a reduction in the response to CVS and could validate a stressor-induced preference for comfort food that in turn could increase body weight. PMID- 22775985 TI - High frequency of copy number alterations in myeloid leukaemia of Down syndrome. PMID- 22775986 TI - A framework for production of systematic review based briefings to support evidence-informed decision-making. AB - BACKGROUND: We have developed a framework for translating existing sources of synthesized and quality-assessed evidence, primarily systematic reviews, into actionable messages in the form of short accessible briefings. The service aims to address real-life problems in response to requests from decision makers.Development of the framework was based on a scoping review of existing resources and our initial experience with two briefing topics, including models of service provision for young people with eating disorders. We also drew on previous experience in dissemination research and practice. Where appropriate, we made use of the SUPporting POlicy relevant Reviews and Trials (SUPPORT) tools for evidence-informed policymaking. FINDINGS: To produce a product that it is fit for this purpose it has been necessary to go beyond a traditional summary of the available evidence relating to effectiveness. Briefings have, therefore, included consideration of cost effectiveness, local applicability, implications relating to local service delivery, budgets, implementation and equity. Our first evidence briefings produced under this framework cover diagnostic endoscopy by specialist nurses and integrated care pathways in mental healthcare settings. CONCLUSIONS: The framework will enable researchers to present and contextualize evidence from systematic reviews and other sources of synthesized and quality-assessed evidence. The approach is designed to address the wide range of questions of interest to decision-makers, especially those commissioning services or managing service delivery and organization in primary or secondary care. Evaluation of the use and usefulness of the evidence briefings we produce is an integral part of the framework and will help to fill a gap in the literature. PMID- 22775987 TI - A fast thermal-curing nanoimprint resist based on cationic polymerizable epoxysiloxane. AB - We synthesized a series of epoxysiloxane oligomers with controllable viscosity and polarity and developed upon them a thermal-curable nanoimprint resist that was cross-linked in air at 110 degrees C within 30 s if preexposed to UV light. The oligomers were designed and synthesized via hydrosilylation of 4-vinyl cyclohexane-1,2-epoxide with poly(methylhydrosiloxane) with tunable viscosity, polarity, and cross-linking density. The resist exhibits excellent chemical and physical properties such as insensitivity toward oxygen, strong mechanical strength, and high etching resistance. Using this resist, nanoscale patterns of different geometries with feature sizes as small as 30 nm were fabricated via a nanoimprint process based on UV-assisted thermal curing. The curing time for the resist was on the order of 10 s at a moderate temperature with the help of UV light preexposure. This fast thermal curing speed was attributed to the large number of active cations generated upon UV exposure that facilitated the thermal polymerization process. PMID- 22775988 TI - Thermodynamic and spectroscopic identification of guest gas enclathration in the double tetra-n-butylammonium fluoride semiclathrates. AB - The precise nature and unique pattern of the double tetra-n-butylammonium fluoride (TBAF) semiclathrates with a guest gas (CH(4) or CO(2)) was closely investigated through thermodynamic and spectroscopic analyses. The three-phase equilibria of semiclathrate (H), liquid water (L(W)), and vapor (V) for the ternary CH(4) + TBAF + water and CO(2) + TBAF + water mixtures with various TBAF concentrations were experimentally measured in order to determine the stability conditions of the double TBAF semiclathrates. The double CH(4) (or CO(2)) + TBAF semiclathrates showed remarkably enhanced thermal stability when compared with pure CH(4) (or CO(2)) hydrate. The highest stabilization effect was observed at the stoichiometric concentration of pure TBAF semiclathrate, which is 3.3 mol %. Gas uptake measurements were undertaken in order to estimate the amount of gas consumed during double semiclathrate formation. CH(4) was found to be a relatively more favorable guest for the 5(12) cages of the double TBAF semiclathrate than CO(2). From the results of the NMR and Raman spectroscopic analyses it was identified that the guest gas molecules (CH(4) or CO(2)) were enclathrated in the 5(12) cages of the double TBAF semiclathrates. The overall results given in this study are useful for understanding the fundamental guest gas enclathration behavior in the double semiclathrates. PMID- 22775989 TI - Inhibition of renin and the (pro)renin receptor system. AB - Renin is the rate-limiting step of the renin-angiotensin system (RAS) and can induce hypertension and cardiovascular diseases (CVDs) through the over-activated renin-angiotensin-converting enzyme (ACE)-angiotensin (Ang) II-Ang II type 1 receptor (AT(1)R) axis. Prorenin and renin bound to the (pro)renin receptor [(P)RR] not only increase the catalytic conversion of angiotensinogen (AGT) to Ang I, but also upregulate the expression of profibrotic genes. This review will discuss the inhibition of renin and the (P)RR system pharmacologically and nutritionally. PMID- 22775990 TI - Expressed emotion as an assessment of family environment with mothers and fathers of 1-year-old children. AB - BACKGROUND: High levels of expressed emotion (EE) in parents have been found to put children at risk for emotional and behavioural problems. However, the majority of existing studies have focused on mothers of school-aged children and adolescents rather than younger children, and have only rarely included fathers. METHODS: The present study examined the reliability of EE in mothers and fathers of 1-year old children. It also investigated whether depression and marital problems in the postnatal period predicted EE toward the child at 12 months. EE was assessed with the Preschool Five Minute Speech Sample in 163 families. RESULTS: The rater-interrater and code-recode reliability was high for most EE dimensions. Mothers and fathers were found to display quite similar EE scores. Regression analyses showed that depression and couple relationship significantly predicted EE in mothers, but not fathers. CONCLUSIONS: The findings suggest that EE provides a reliable and useful assessment of the family environment in families of young children. PMID- 22775991 TI - Review of ethnic disparities in access to renal transplantation. AB - Renal transplantation is the gold standard treatment for patients with end-stage renal disease and is associated with several advantages over dialysis, including increased quality of life, reduced morbidity and mortality, and lower healthcare costs. Barring the constraints of a limited organ supply, the goals of the patient care should focus on attaining renal transplantation while minimizing, or even eliminating, time spent on dialysis. Disparities in access to renal transplantation between African Americans and Caucasians have been extensively documented, with African Americans having significantly poorer access. There is a growing corpus of literature examining the determinants of reduced access among other racial ethnic minority groups, including Hispanics. These determinants include patient and physician preference, socioeconomic status, insurance type, patient education, and immunologic factors. We review these determinants in access to renal transplantation in the United States among all races and ethnicities. PMID- 22775992 TI - Human skin cancer stem cells: a tale of mice and men. AB - Carcinomas, cancers of epithelial tissues, are the commonest malignancies and cause the greatest cancer mortality worldwide. Among these, the incidence of keratinocyte-derived non-melanoma skin cancers (NMSC), by far the greatest, is increasing rapidly. Yet despite access to tumor tissue, acceptance of human NMSC as a model carcinoma has been hindered by the lack of a reliable xenograft model. Instead, we have relied on the murine two-step carcinogenesis protocol as a reproducible squamous cell carcinoma (SCC) model, but this differs from their human counterpart in cause, site, genetic basis and biological behaviour. By xeno engraftment of primary human SCC, we were recently successful in demonstrating the presence of primary human SCC cancer stem cells or tumor-initiating cells. These findings once more align the study human SCC as the archetypal carcinoma model. In this review, we describe the evidence for the existence of tumor initiating cells, with emphasis on skin cancer, limiting our discussions to primary human cancer studies where possible. PMID- 22775993 TI - Animal models of wound repair: Are they cutting it? AB - Current understanding of the complex process of wound repair is based on decades of study. Integral to this understanding has been the use of in vitro and in vivo models to uncover the key molecular players. Now that major wound processes are more fully understood, therapeutic strategies can be developed to manipulate wound repair. Particularly important areas for future research include developing therapies to aid treatment of healing pathologies such as chronic wounds, and manipulating the normal healing processes to drive a more regenerative phenotype in adults. Here, we discuss the benefits and limitations of current animal-based models and highlight the urgent need for improved predictive preclinical models for wound healing research. We conclude by suggesting directions where more robust models of chronic wound pathologies may arise, expediting the development of novel therapies. PMID- 22775994 TI - The absence of Brm exacerbates photocarcinogenesis. AB - Brm is an ATPase subunit of the SWI/SNF chromatin-remodelling complex. Previously, we identified a novel hotspot mutation in Brm in human skin cancer, which is caused by exposure to ultraviolet radiation (UVR). As SWI/SNF is involved in DNA repair, we investigated whether Brm-/- mice had enhanced photocarcinogenesis. P53+/- and Brm-/-p53+/- mice were also examined as the p53 tumor suppressor gene is mutated early during human skin carcinogenesis. Mice were exposed to a low-dose irradiation protocol that caused few skin tumors in wild-type mice. Brm-/- mice with both p53 alleles intact had an increased incidence of skin and ocular tumors compared to Brm+/+p53+/+ controls. Brm loss in p53+/- mice did not further enhance skin or ocular cancer incidence beyond the increased photocarcinogenesis in p53+/- mice. However, the skin tumors that arose early in Brm-/- p53+/- mice had a higher growth rate. Brm-/- did not prevent UVR induced apoptotic sunburn cell formation, which is a protective response. Unexpectedly, Brm-/- inhibited UVR-induced immunosuppression, which would be predicted to reduce rather than enhance photocarcinogenesis. In conclusion, the absence of Brm increased skin and ocular photocarcinogenesis. Even when one allele of p53 is lost, Brm has additional tumor suppressing capability. PMID- 22775995 TI - Collagen XVII (BP180) modulates keratinocyte expression of the proinflammatory chemokine, IL-8. AB - Collagen XVII (COL17), a transmembrane protein expressed in epidermal keratinocytes (EK), is targeted by pathogenic autoantibodies in bullous pemphigoid. Treatment of EK with anti-COL17 autoantibodies triggers the production of proinflammatory cytokines. In this study, we test the hypothesis that COL17 is involved in the regulation of the EK proinflammatory response, using IL-8 expression as the primary readout. The absence of COL17 in EK derived from a junctional epidermolysis bullosa patient or shRNA-mediated knockdown of COL17 in normal EK resulted in a dysregulation of IL-8 responses under various conditions. The COL17-deficient cells showed an abnormally high IL-8 response after treatment with lipopolysaccharide (LPS), ultraviolet-B radiation or tumor necrosis factor, but exhibited a blunted IL-8 response to phorbol 12-myristate 13 acetate exposure. Induction of COL17 expression in COL17-negative EK led to a normalization of the LPS-induced proinflammatory response. Although alpha6beta4 integrin was found to be up-regulated in COL17-deficient EK, siRNA-mediated knockdown of the alpha6 and beta4 subunits revealed that COL17's effects on the LPS IL-8 response are not dependent on this integrin. In LPS-treated cells, inhibition of NF-kappa B activity in COL17-negative EK resulted in a normalization of their IL-8 response, and expression of an NF-kappa B-driven reporter was shown to be higher in COL17-deficient, compared with normal EK. These findings support the hypothesis that COL17 plays an important regulatory role in the EK proinflammatory response, acting largely via NF-kappa B. Future investigations will focus on further defining the molecular basis of this novel control network. PMID- 22775996 TI - The G60S Cx43 mutant enhances keratinocyte proliferation and differentiation. AB - Transient knock-down of the gap junction protein Cx43 by antisense and siRNA, or gap junction block with mimetic peptides, have been shown to enhance epidermal wound healing. However, patients with oculodentodigital dysplasia (ODDD) express mutant Cx43 that leads to a chronic reduction in gap junctional intercellular communication. To determine whether mutant Cx43 in keratinocytes would impact upon the wound healing process, we localized Cx43 in human and mouse skin tissue expressing mutant Cx43 and assessed the ability of primary keratinocytes derived from a mouse model of ODDD to proliferate, migrate and differentiate. In the epidermis from an ODDD patient and in the epidermis of mice expressing the G60S mutant or in keratinocytes obtained from mutant mice, Cx43 was frequently found within intracellular compartments and rarely localized to punctate sites of cell cell apposition. Primary keratinocytes derived from G60S mutant mice proliferated faster but migrated similarly to keratinocytes derived from wild-type control mice. Keratinocytes derived from mutant mice expressed abundant Cx43 and higher levels of involucrin and loricrin under low calcium conditions. However, after calcium-induced differentiation, similar levels of Cx43, involucrin and loricrin were observed. Thus, we conclude that during wound healing, mutant Cx43 may enhance keratinocyte proliferation and promote early differentiation of keratinocytes. PMID- 22775997 TI - Light-activated nanofibre textiles exert antibacterial effects in the setting of chronic wound healing. AB - The maintenance of an aseptic environment for chronic wounds is one of the most challenging tasks in the wound-healing process. Furthermore, the emergence of antibiotic-resistant bacterial strains is on the rise, rendering conventional treatments less effective. A new antibacterial material consisting of a polyurethane Tecophilic(TM) nanofibre textile (NT) that was prepared by electrospinning and doped by a tetraphenylporphyrin (TPP) photosensitizer activated by visible light was tested for use in wound beds and bandages. In vitro experiments were performed to assess the antibacterial activity of the textile against three bacterial strains. Furthermore, the new textile was tested in 162 patients with chronic leg ulcers. A complete inhibition of in vitro growth of the three tested bacterial strains was observed on the surface of NTs that had been illuminated with visible light and was clinically demonstrated in 89 patients with leg ulcers. The application of the textiles resulted in a 35% decrease in wound size, as assessed via computer-aided wound tracing. Wound related pain, which was estimated using a visual analogue scale, was reduced by 71%. The results of this trial reveal that the photoinactivation of bacteria through the photosensitized generation of short-lived, highly reactive singlet oxygen O(2) ((1) Delta(g) ) results in relatively superficial antibacterial effects in comparison with standard antiseptic treatment options. Thus, such treatment does not interfere with the normal healing process. This method therefore represents a suitable alternative to the use of topical antibiotics and antiseptics and demonstrates potentially broad applications in medicine. PMID- 22775998 TI - Identification and validation of reference genes for expression studies in human keratinocyte cell lines treated with and without interferon-gamma - a method for qRT-PCR reference gene determination. AB - Based on the exquisite sensitivity, reproducibility and wide dynamic range of quantitative reverse-transcription real-time polymerase chain reaction (qRT-PCR), it is currently the gold standard for gene expression studies. Target gene expression is calculated relative to a stably expressed reference gene. An ideal reference should be uniformly expressed during all experimental conditions within the given experimental system. However, no commonly applicable 'best' reference gene has been identified. Thus, endogenous controls must be determined for every experimental system. As no appropriate reference genes have been reported for immunological studies in keratinocytes, we aimed at identifying and validating a set of endogenous controls for these settings. An extensive validation of sixteen possible endogenous controls in a panel of 8 normal and transformed keratinocyte cell lines in experimental conditions with and without interferon-gamma was performed. RNA and cDNA quality was stringently controlled. Candidate reference genes were assessed by TaqMan((r)) qRT-PCR. Two different statistical algorithms were used to determine the most stably and reproducibly expressed housekeeping genes. mRNA abundance was compared and reference genes with widely different ranges of expression than possible target genes were excluded. Subsequent geNorm and NormFinder analyses identified GAPDH, PGK1, IPO8 and PPIA as the most stably expressed genes in the keratinocyte panel under the given experimental conditions. We conclude that the geometric means of expression values of these four genes represents a robust normalization factor for qRT-PCR analyses in interferon-gamma-dependent gene expression studies in keratinocytes. The methodology and results herein may help other researchers by facilitating their choice of reference genes. PMID- 22775999 TI - Protective effect of chromene isolated from Sargassum horneri against UV-A induced damage in skin dermal fibroblasts. AB - Skin homoeostasis is interrupted during UV-A irradiation. How the UV-A-altered skin components influences photoageing of skin should be investigated using human in vitro models that are important for understanding skin ageing. In this study, chromene compound, sargachromenol, was isolated from Sargassum horneri, and its potency on inhibition of photoageing was investigated in UV-A-irradiated dermal fibroblasts. Effects of sargachromenol on the prevention of photoageing were evaluated by measuring ROS production, membrane protein oxidation, lipid peroxidation and ageing-related gene expression in UV-A-irradiated human skin dermal fibroblasts. The results indicated that treatment with sargachromenol suppressed the collagenase matrix metalloproteinases (MMPs), MMP-1, MMP-2 and MMP 9 expression without any cytotoxicity and phototoxicity. It was further found that these inhibitions were because of increase in the expression of TIMP-1 and TIMP-2 genes. Furthermore, we confirmed that the UV-A-induced transcriptions of AP-1 signalling pathway were regulated by sargachromenol treatment in UV-A irradiated dermal fibroblasts. PMID- 22776000 TI - Primary cutaneous anaplastic large cell lymphoma shows a distinct miRNA expression profile and reveals differences from tumor-stage mycosis fungoides. AB - The miRNA expression profiles of skin biopsies from 14 primary cutaneous anaplastic large cell lymphoma (C-ALCL) patients were analysed with miRNA microarrays using the same control group of 12 benign inflammatory dermatoses (BID) as previously used to study the miRNA expression profile of tumor-stage mycosis fungoides (MF). We identified 13 differentially expressed miRNAs between C-ALCL and BID. The up-regulation of miR-155, miR-27b, miR-30c and miR-29b in C ALCL was validated by miRNA-Q-PCR on independent study groups. Additionally, the miRNA expression profiles of C-ALCL were compared with those of tumor-stage MF. Although miRNA microarray analysis did not identify statistically significant differentially expressed miRNAs, miRNA-Q-PCR demonstrated statistically significantly differential expression of miR-155, miR-27b, miR-93, miR-29b and miR-92a between tumor-stage MF and C-ALCL. This study, the first describing the miRNA expression profile of C-ALCL, reveals differences with tumor-stage MF, suggesting a different contribution to the pathogenesis of these lymphomas. PMID- 22776001 TI - Up-regulation of melanin synthesis by the antidepressant fluoxetine. AB - Fluoxetine, a member of the class of selective serotonin reuptake inhibitors, is a potent antidepressant commonly used in clinical practice. Here, we report that fluoxetine increases cellular tyrosinase (TYR) activity, enhances the protein levels of microphthalmia-associated transcription factor (MITF), TYR and tyrosinase-related protein-1 (TRP-1) and eventually leads to a dramatic increase in melanin production in both murine B16F10 melanoma cells and normal human melanocytes (NHMCs). In well-characterized C57BL/6 mouse models, systemic application of fluoxetine increased hair pigmentation by up-regulating hair follicular MITF, TYR, TRP-1 and tyrosinase-related protein-2 (TRP-2) protein levels. Using a serotonin 1A receptor (SR1A) antagonist and RNA interference (RNAi) technique, we revealed that SR1A appears to be one of the involved pathways in the fluoxetine-induced melanogenesis in B16F10 cells. These results suggest that fluoxetine may hold a significant therapeutic potential for treating skin hypopigmentation disorders, and SR1A may serve as a novel target in modulating melanogenesis. PMID- 22776002 TI - Polypodium leucotomos decreases UV-induced epidermal cell proliferation and enhances p53 expression and plasma antioxidant capacity in hairless mice. AB - A single dose of ultraviolet radiation (UVR) induces significant changes in blood and skin of hairless mice. Oral administration of a hydrophilic extract of the fern Polypodium leucotomos (PL, 300 mg/kg during 5 days before UVR and for two additional days after irradiation) modulates some of the effects of UVR. Most significantly, PL administration reduced the number of proliferating cells by 13%, increased the number of p53(+) cells by 63%, enhanced the antioxidant plasma capacity (ORAC) by 30% and reinforced the network of dermal elastic fibres. Western blot analysis of skin antioxidant-related enzymes failed to demonstrate significant changes caused by PL. Thus, the beneficial effect of PL likely owes to its antioxidant and anti-ROS properties rather than its modulation of the expression of endogenous antioxidant systems. These data provide mechanistic clues for its efficacy as a systemic photoprotective agent with antioxidant and anti-photo-ageing properties. PMID- 22776004 TI - Smoking among troops deployed in combat areas and its association with combat exposure among navy personnel in Sri Lanka. AB - BACKGROUND: Among military personnel alcohol consumption and binge-drinking have increased but cigarette smoking has declined in the recent past. Although there is a strong association between smoking and PTSD the association between combat exposure and smoking is not clear. METHODS: This cross sectional study was carried out among representative samples of SLN Special Forces and regular forces deployed in combat areas. Both Special Forces and regular forces were selected using simple random sampling. Only personnel who had served continuously in combat areas during the one year period prior to end of combat operations were included in the study. Females were not included in the sample. The study assessed several mental health outcomes as well as alcohol use, smoking and cannabis use. Sample was classified according to smoking habits as never smokers, past smokers (those who had smoked in the past but not within the past year) and current smokers (those smoking at least one cigarette within the past 12 months). RESULTS: Sample consisted of 259 Special Forces and 412 regular navy personnel. Prevalence of current smoking was 17.9% (95% CI 14.9-20.8). Of the sample 58.4% had never smoked and 23.7% were past smokers. Prevalence of current smoking was significantly higher among Special Forces personnel compared to regular forces. (OR 1.90 (95% CI 1.20-3.02). Personnel aged >= 35 years had the lowest prevalence of smoking (14.0%). Commissioned officers had a lower prevalence (12.1%) than non commissioned officers or other ranks. After adjustment for demographic variables and service type there was significant association between smoking and combat experiences of seeing dead or wounded [OR 1.79 (95%CI 1.08-2.9)], handling dead bodies [OR 2.47(95%CI 1.6-3.81)], coming under small arms fire [OR 2.01(95%CI 1.28-3.15)] and coming under mortar, missile and artillery fire [OR 2.02(95%CI 1.29-3.17)]. There was significant association between the number of risk events and current smoking [OR 1.22 (95%CI1.11-1.35)]. CONCLUSIONS: There was significant association between current smoking and combat experiences. Current smoking was strongly associated with current alcohol use. Prevalence of current smoking was less among military personnel than in the general population. Prevalence of smoking was significantly higher among Special Forces personnel. PMID- 22776003 TI - Lipid rafts association and anti-apoptotic function of prohibitin in ultraviolet B light-irradiated HaCaT keratinocytes. AB - Upon UVB irradiation, an alternation of major lipid raft components can lead to the recruitment/activation of rafts-associated proteins and initiation of downstream apoptotic signalling pathways. We used two-dimensional gel electrophoresis (2-DE) to identify potential regulators of UVB-induced apoptosis and mass spectrometry fingerprint analysis to identify proteins that are altered in the rafts after UVB irradiation. Our data show that levels of several proteins, including prohibitin (PHB), were changed in lipid rafts after UVB irradiation. We also demonstrate that while total PHB expression was not changed, the protein was enriched in lipid rafts after UVB irradiation. Reduced expression of PHB using siRNA knockdown resulted in an increase in cellular apoptosis after UVB irradiation. Based on these results, we propose that PHB protects keratinocytes from UVB-induced apoptosis. PMID- 22776006 TI - Effect of L-ascorbic Acid on the climbing ability and protein levels in the brain of Drosophila model of Parkinson's disease. AB - In the present study, the effect of l-ascorbic acid (AA) was studied on the climbing ability of the Parkinson's disease (PD) model Drosophila expressing normal human alpha synuclein (h-alphas) in the neurons. These flies show locomotor dysfunction as the age progresses. AA at final concentration of 11.35 * 10(-5) M, 22.71 * 10(-5) M, 45.42 * 10(-5) M, and 68.13 * 10(-5) M was added to the diet, and the flies were allowed to feed for 21 days. AA at 11.35 * 10(-5) M did not show any significant delay in the loss of climbing ability of PD model flies. However, AA at 22.71 * 10(-5) M, 45.42 * 10(-5) M, and 68.13 * 10(-5) M showed a dose dependent significant (p < .05) delay in the loss of climbing ability of PD model flies as compared to the untreated PD flies. The total protein concentration in brain homogenate was measured in treated as well as control groups after 21 days, no significant difference was obtained between treated as well as control (PD flies and l-dopa) groups. The results suggest that AA is potent in delaying the climbing disability of the PD model flies expressing h-alphas in the neurons. PMID- 22776007 TI - The dissonant care management of illicit drug users in medical wards, the views of nurses and patients: a grounded theory study. AB - AIMS: The aim of this study was to explore how registered nurses manage and deliver care to patients admitted to medical wards and Medical Assessment Units with complications of drug use and to elicit the experiences and views of those receiving that care. BACKGROUND: Illicit drug use is a major public health problem worldwide. The physical complications of problem drug use often result in admission to medical wards. Registered nurses working in these settings have been reported as possessing negative attitudes towards patients who use illicit drugs and lacking preparation to provide problem drug use-related care needs. DESIGN: Grounded theory. METHODS: A grounded theory approach was used to collect and analyse 41 semi-structured interviews. Data collection and analysis were undertaken in nine medical wards in the Northwest of England in 2008. A combination of purposive and theoretical sampling was adopted to recruit registered nurses (n=29) and medical ward patients (n=12) admitted for physical complications of problem drug use. Data were subjected to constant comparative analysis. FINDINGS: Two sub-categories emerged: 'Lack of knowledge to care' and 'Distrust and detachment' and these formed the core category 'Dissonant care'. The combination of lack of educational preparation, negative attitudes and experience of conflict, aggression, and untrustworthiness appeared to affect negatively the nurse-patient relationship. CONCLUSIONS: This study illuminated interplay of factors that complicated the delivery of care. The complexity of caring for patients who are pre-judged negatively by nurses appears to engender dissonance and disparities in care delivery. Better education and training, coupled with role support about problem drug use may reduce conflict, disruption, and violence and facilitate competent care for these patients. PMID- 22776008 TI - The frequencies of human neutrophil alloantigens among the Japanese population. AB - Human neutrophil antigens (HNAs) play an important role in a variety of clinical conditions including immune-mediated neutropenia, non-hemolytic transfusion reactions, and transfusion-related acute lung injury. The aim of this study was to investigate the frequency distribution of HNAs-1 to -5 among the Japanese population. We analyzed samples from 570 healthy Japanese by molecular and serologic techniques to estimate the gene frequencies of HNAs-1 to -5. DNA samples were obtained and typed for the HNA-1 (n = 523), -3 (n = 570), -4 (n = 570), and -5 (n = 508), by molecular techniques. The HNA-1 genotype was determined by using a commercial polymerase chain reaction-reverse sequence specific oligonucleotide probes (PCR-rSSOP) kit. The HNA-3 to -5 genotypes were determined by the PCR-sequence specific primer (PCR-SSP), previously described, with a small modification. The HNA-2a phenotype was determined in 301 donors by granulocyte immunofluorescence test. In Japanese, the gene frequencies of HNA-1a, -1b, and -1c were 0.623, 0.377, and 0.000, respectively. The frequency of HNA-2a phenotype was 0.987, and the gene frequencies of HNA-3a and -3b were 0.654 and 0.346, respectively. HNA-4a and -4b were found at 1.000 and 0.000, respectively, and HNA-5a and -5b at 0.840 and 0.160, respectively. We describe, for the first time, the frequencies of all HNAs (HNA-1 to -5) among the Japanese population. This study will be helpful for the prediction of the risk of alloimmunization to HNA, especially to determine the risk of HNA alloantibody production by transfusion of HNA incompatible blood and feto-maternal incompatibility. PMID- 22776009 TI - Development of a suspension microarray for the genotyping of African swine fever virus targeting the SNPs in the C-terminal end of the p72 gene region of the genome. AB - African swine fever virus (ASFV) causes one of the most dreaded transboundary animal diseases (TADs) in Suidae. African swine fever (ASF) often causes high rates of morbidity and mortality, which can reach 100% in domestic swine. To date, serological diagnosis has the drawback of not being able to differentiate variants of this virus. Previous studies have identified the 22 genotypes based on sequence variation in the C-terminal region of the p72 gene, which has become the standard for categorizing ASFVs. This article describes a genotyping assay developed using a segment of PCR-amplified genomic DNA of approximately 450 bp, which encompasses the C-terminal end of the p72 gene. Complementary paired DNA probes of 15 or 17 bp in length, which are identical except for a single nucleotide polymorphism (SNP) in the central position, were designed to either individually or in combination differentiate between the 22 genotypes. The assay was developed using xMAP technology; probes were covalently linked to microspheres, hybridized to PCR product, labelled with a reporter and read in the Luminex 200 analyzer. Characterization of the sample was performed by comparing fluorescence of the paired SNP probes, that is, the probe with higher fluorescence in a complementary pair identified the SNP that a particular sample possessed. In the final assay, a total of 52 probes were employed, 24 SNP pairs and 4 for general detection. One or more samples from each of the 22 genotypes were tested. The assay was able to detect and distinguish all 22 genotypes. This novel assay provides a powerful novel tool for the simultaneous rapid diagnosis and genotypic differentiation of ASF. PMID- 22776010 TI - Testosterone replacement therapy improves erythrocyte membrane lipid composition in hypogonadal men. AB - AIM: The aim of this study was to investigate the effects of testosterone replacement therapy (TRT) on erythrocyte membrane (EM) lipid composition and physico-chemical properties in hypogonadal men. METHODS: EM isolated from three patients before and after TRT with injectable testosterone undecanoate or testosterone gel were used for analysis of the phospholipid and fatty acid composition, cholesterol/phospholipid ratio, membrane fluidity, ceramide level and enzyme activities responsible for sphingomyelin metabolism. RESULTS: TRT induced increase of phosphatidylethanolamine (PE) in the EMs and sphingomyelin. Reduction of the relative content of the saturated palmitic and stearic fatty acids and a slight increase of different unsaturated fatty acids was observed in phosphatidylcholine (PC). TRT also induced decrease of the cholesterol/total phospholipids ratio and fluidization of the EM. DISCUSSION: The TRT induced increase of PE content and the reduction of saturation in the PC acyl chains induced alterations in the structure of EM could result in higher flexibility of the erythrocytes. The increase of the SM-metabolizing enzyme neutral sphingomyelinase, which regulates the content of ceramide in membranes has a possible impact on the SM signaling pathway. CONCLUSION: We presume that the observed effect of TRT on the composition and fluidity of the EM contributes for improvement of blood rheology and may diminish the thrombosis risk. Larger studies are needed to confirm the findings of this pilot study. PMID- 22776011 TI - An expanded view of self-management: patients' perceptions of education and support in an intervention for chronic musculoskeletal pain. AB - OBJECTIVES: Chronic pain is prevalent, costly, and is associated with profound psychological effects. Although pain is prevalent in returning veterans of the recent military conflicts in Afghanistan and Iraq (Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn [OEF/OIF/OND] Veterans), little is known about chronic pain in these patients. This study's objective was to ascertain perceptions of a multicomponent intervention tested in a randomized controlled trial for OEF/OIF/OND veterans with chronic musculoskeletal pain (Evaluation of Stepped Care for Chronic Pain [ESCAPE]). DESIGN: Qualitative interviews were conducted with 26 patients in the intervention arm of ESCAPE (21% of total intervention patients) to determine patients' experiences with and perceptions of the intervention. Patients were purposefully sampled to include treatment responders (defined as >=30% reduction in pain-related disability or pain severity), nonresponders, and noncompleters (completed <50% of trial). Qualitative analysis was guided by grounded theory. RESULTS: Both responders and nonresponders discussed the importance of the self-management education they received. Of particular significance, patients identified the nurse care manager who administered the intervention as being integral to patients' ability to self manage their chronic pain. Patients described important ways in which the nurse facilitated their self-management, reported under three themes: 1) helping patients find what works for their pain; 2) holding patients accountable for their pain management; 3) motivating and providing emotional support to patients. CONCLUSIONS: Results corroborate previous work and suggest that current conceptualizations of self-management are incomplete. A model is proposed that not only depicts self-management as involving more than activities and strategies, but also acknowledges the central role of relationships and support in pain self-management. PMID- 22776012 TI - Tumor growth inhibitory effect of ADAMTS1 is accompanied by the inhibition of tumor angiogenesis. AB - Angiogenesis plays an important role in tumor progression. Several reports have demonstrated that a disintegrin and metalloproteinase with thrombospondin motifs1 (ADAMTS1) inhibited angiogenesis via multiple mechanisms. The aim of this study was to investigate the effect of ADAMTS1 on endothelial cells in vitro and on tumor growth with regard to angiogenesis in vivo. We examined the effects of the transfection of ADAMTS1 using two constructs, full-length ADAMTS1 (full ADAMTS1) and catalytic domain-deleted ADAMTS1 (delta ADAMTS1). Transfection of both the full ADAMTS1 and delta ADAMTS1 gene constructs demonstrated the secretion of tagged-ADAMTS1 protein into the conditioned medium, so we examined the effects of ADAMTS1-containing conditioned medium on endothelial cells. Both types of conditioned media inhibited endothelial tube formation, and this effect was completely abolished after immunoprecipitation of the secreted protein from the medium. Both types of conditioned media also inhibited endothelial cell migration and proliferation. We then examined the impact of ADAMTS1 on endothelial cell apoptosis. Both conditioned media increased the number of Annexin V-positive endothelial cells and caspase-3 activity and this effect was attenuated when z vad was added. These results indicated that ADAMTS1 induced endothelial cell apoptosis. We next examined the effects of ADAMTS1 gene transfer into tumor bearing mice. Both full ADAMTS1 and delta ADAMTS1 significantly inhibited the subcutaneous tumor growth. Collectively, our results demonstrated that ADAMTS1 gene transfer inhibited angiogenesis in vitro and in vivo, likely as a result of the induction of endothelial cell apoptosis by ADAMTS1 that occurs independent of the protease activity. PMID- 22776013 TI - Cerebrospinal fluid viral breakthrough in two HIV-infected subjects on darunavir/ritonavir monotherapy. AB - Darunavir/ritonavir monotherapy maintains HIV suppression in most patients who have achieved an undetectable viral load on combination antiretroviral treatment, and is increasingly used in the clinic. However, concerns have been raised about the effectiveness of ritonavir-boosted protease inhibitor (PI/r) monotherapy in the prevention of HIV replication in the central nervous system (CNS). Here we report the cases of 2 patients on darunavir/r maintenance monotherapy with cerebrospinal fluid viral breakthrough together with increased immunoactivation and biomarker signs of neuronal injury. These 2 cases raise concerns about the effectiveness of darunavir/ritonavir monotherapy in HIV CNS infection. Thus, we recommend caution with protease inhibitor monotherapy until CNS results have been obtained from clinical studies. PMID- 22776014 TI - Effects of once-daily teneligliptin on 24-h blood glucose control and safety in Japanese patients with type 2 diabetes mellitus: a 4-week, randomized, double blind, placebo-controlled trial. AB - AIM: To assess blood glucose control over 24 h and the safety of teneligliptin 10 and 20 mg, a novel dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. METHODS: Ninety-nine patients were administered teneligliptin 10 or 20 mg or placebo before breakfast for 4 weeks in a randomized, double-blind, placebo-controlled, parallel-group study. RESULTS: Both teneligliptin-treated groups showed significantly smaller 2-h postprandial glucose (2-h PPG), 24-h mean glucose and fasting plasma glucose values than the placebo group. The differences between the teneligliptin 10 mg and placebo groups in changes in 2-h PPG after each meal were -50.7 +/- 7.8, -34.8 +/- 9.2 and -37.5 +/- 7.5 mg/dl at breakfast, lunch and dinner, respectively [least-squares (LS) means +/- standard error (s.e.), all, p < 0.001]. The corresponding LS means +/- s.e. for teneligliptin 20 mg versus placebo were -38.1 +/- 7.8, -28.6 +/- 9.2 and -36.1 +/- 7.5 mg/dl, respectively (p < 0.001, p < 0.01, p < 0.001, respectively). Both doses of teneligliptin increased postprandial plasma active glucagon-like peptide-1 concentrations compared with placebo. The incidence of adverse events and drug-related adverse events was similar among groups. There were no hypoglycaemic symptoms or serious adverse events. CONCLUSIONS: Once-daily teneligliptin improved blood glucose levels over 24 h without hypoglycaemia. PMID- 22776015 TI - A prospective analysis of implementation of multi-disciplinary team decisions in breast cancer. AB - Multi-disciplinary teams (MDTs) management of patients with cancer is mandatory in the United Kingdom, and auditing team decision-making by examining rates of decision implementation and reasons for nonimplementation may inform this practice. Consecutive breast cancer MDT decisions, subsequent decision implementation, and reasons for nonimplementation were prospectively recorded. Factors associated with nonimplementation of the MDT decision were analyzed with logistic regression. Of 289 consecutive MDT decisions involving 210 women, 20 (6.9%, 95% CIs 4.3%-10.5%) were not implemented. Most changed MDT decisions did so because of patient preferences (n = 13, 65%), with the discovery of new clinical information (n = 3) and individual doctor's views (n = 4) also leading to decision nonimplementation. MDT decisions were significantly less likely to be adhered to in patients with confirmed malignant disease compared to those with benign or 'unknown' disease categories (p < 0.001) and MDT decisions in older patients were significantly more likely not to be implemented than in younger patients (p = 0.002). Auditing nonimplementation of MDT recommendations and examining reasons for changed decisions is a useful process to monitor team performance and to identify factors that need more attention during the MDT meeting to ensure that the process makes optimal patient centered decisions. PMID- 22776016 TI - Should recipients with obstructive uropathy undergo close surveillance for BK virus infection post-transplant? PMID- 22776017 TI - Protein modification as oxidative stress marker in normal and pathological human seminal plasma. AB - OBJECTIVE: Our study aims to assess the oxidative stress status of seminal plasma from normozoospermic, azoospermic, and leukocytospermic males, since abnormal sperm and leukocytes in human ejaculates are the main source of reactive oxygen species (ROS) which lead to oxidative damages. For this purpose we applied a biochemical approach to the assessment of the oxidative stress status by using two-dimensional (2D) electrophoresis to check the level of protein oxidation after specific labeling of free thiol (-SH) groups. METHODS: Seminal plasma samples from normal and pathological males were analyzed by a luminol-based chemiluminescent assay. The same samples after specific labeling of free -SH groups with 3-N-maleimidopropionyl biocytin, were analyzed by 2D electrophoresis and computer-assisted semiquantitative determination of the amount of free -SH groups. RESULTS: Using a standard chemiluminescence assay, we demonstrated a high, low and normal level of ROS, respectively, in seminal plasma from leukocytospermic, azoospermic, and normozoospermic subjects. By 2D electrophoresis and streptavidin blotting of specifically labeled free -SH groups of proteins, we detected in the same samples a higher level of oxidated SH groups comparable between azoospermic and leukocytospermic samples, whereas a significantly higher level of free -SH groups was detected in normozoospermic subjects. DISCUSSION: Our results demonstrated that a pathological oxidative stress status in seminal plasma may be revealed by the levels of the protein free -SH groups, both in the presence or absence of cells. PMID- 22776018 TI - Variation: use it or misuse it--replication and its variants. PMID- 22776019 TI - Bell's palsy - the effect of prednisolone and/or valaciclovir versus placebo in relation to baseline severity in a randomised controlled trial. AB - OBJECTIVES: To evaluate the treatment effect of prednisolone and/or valaciclovir in Bell's palsy patients with different baseline severity of palsy. DESIGN: Patient data were collected from the Scandinavian Bell's Palsy Study, a prospective, randomised, double-blind, placebo-controlled, multi-centre trial. SETTING: Sixteen otorhinolaryngological centres in Sweden and one in Finland. PARTICIPANTS: Altogether, 829 patients aged 18-75 years were treated within 72 h of palsy onset. Patients were randomly assigned to treatment with prednisolone plus placebo (n = 210), valaciclovir plus placebo (n = 207), prednisolone plus valaciclovir (n = 206), placebo plus placebo (n = 206). Follow-up was 12 months. MAIN OUTCOME MEASURES: Facial function was assessed using the Sunnybrook grading scale at baseline and at 12 months. Complete recovery was defined as Sunnybrook score = 100. RESULTS: All patients, regardless of baseline severity, showed significantly higher complete recovery rates if treated with prednisolone compared with no prednisolone. In patients with severe palsy, recovery at 12 months was 51% with prednisolone treatment versus 31% without prednisolone (P = 0.02). Corresponding results were 68%versus 51% (P = 0.004) for moderate, and 83%versus 73% (P = 0.02) for mild palsy. In patient groups with moderate and mild palsy at baseline, significantly fewer prednisolone-treated patients had synkinesis at 12 months (P = 0.04 and P < 0.0001, respectively). For patients with severe palsy at baseline, prednisolone versus no prednisolone made no significant difference regarding synkinesis at 12 months. Valaciclovir did not add any significant effect to prednisolone regarding recovery rate or synkinesis at 12 months. CONCLUSION: Prednisolone treatment resulted in higher complete recovery rates, regardless of severity at baseline. Prednisolone treatment should be considered in all patients irrespective of degree of palsy. PMID- 22776020 TI - Diagnosis of BCC by multiphoton laser tomography. AB - BACKGROUND/PURPOSE: Multiphoton Laser Tomography (MPT) is a non-linear optical technique that gives access to morphology and structure of both cells and extracellular matrix of the skin through the combination of autofluorescence imaging and second harmonic generation (SHG). The aim of this study was to identify MPT descriptors on ex vivo specimens of basal cell carcinoma (BCC) to assess the sensitivity and specificity of these criteria for the diagnosis of BCC and its differentiation from other skin tumours, inflammatory diseases and healthy skin. METHODS: In the preliminary study, MPT images referring to 24 BCCs and 24 healthy skin samples were simultaneously evaluated by three observers for the identification of features characteristic of BCC. In the main study, the presence/absence of the descriptors identified in the preliminary study was blindly evaluated on a test set, comprising 66 BCCs, 66 healthy skin samples and 66 skin lesions, including 23 nevi, 8 melanomas, 17 skin tumours and other skin lesions by 3 independent observers. RESULTS: In the preliminary study, three epidermal descriptors and six descriptors for BCC were identified. The latter included aligned elongated cells, double alignment of cells, cell nests with palisading and phantom islands. From the test set, 56 BCCs were correctly diagnosed, whereas in 10 cases the diagnosis was 'other lesions'. However, it was always possible to exclude the diagnosis of BCC in healthy skin and other lesion samples. Thus, overall sensitivity of the method was 84.85, whereas a specificity of 100% was observed with respect to both healthy skin and 'other lesions'. CONCLUSIONS: This study describes new morphological descriptors of BCC enabling its characterization and its distinction from healthy skin and other skin lesions in ex vivo samples, and demonstrates for the first time that MPT represents a sensitive and specific technique for the diagnosis of BCC. PMID- 22776021 TI - Use of complementary and alternative therapy among patients with rheumatoid arthritis and osteoarthritis. AB - AIMS AND OBJECTIVES: We wanted to assess the prevalence of complementary and alternative therapy use among patients suffering from rheumatoid arthritis or osteoarthritis in the Lebanese population and to determine the perceived efficacy and side effects of complementary and alternative therapy in the treatment of these diseases. BACKGROUND: Complementary and alternative therapy has become popular among patients with chronic illnesses because of its widespread use. Rheumatoid arthritis and osteoarthritis are two diseases associated with severe pain, inflammation and limited activity. Although both are quite common in Lebanon, no studies were conducted in our country to portray complementary and alternative therapy use in their treatment. DESIGN: Descriptive cross-sectional study. METHODS: Conducted individualised questionnaire-based interviews among 250 adult patients, ranging between the ages of 20-90 years and diagnosed with either rheumatoid arthritis or osteoarthritis. The questionnaire included demographic information, clinical information, use of conventional therapies and complementary and alternative therapy, and the disease status before and after complementary and alternative therapy use. RESULTS: Fifty-eight (23.2%) patients used complementary and alternative therapy in addition to their conventional medications in the treatment of either rheumatoid arthritis or osteoarthritis. Most herbal medicine users (63.8%) believed that complementary and alternative therapy was beneficial. The disease status measured by the intensity of pain, sleeping pattern and level of activities was significantly improved after using complementary and alternative therapy (p =0.01). Forty-eight (82.75%) patients were using herbals as complementary and alternative therapy, 14 (24.1%) of whom have sought medical care because of potential concomitant drug-complementary and alternative therapy side effects. However, these side effects were not serious and reversible. CONCLUSION AND RECOMMENDATIONS: Although complementary and alternative therapy might have beneficial effects in rheumatoid arthritis and osteoarthritis, patients should be cautious about their use and should necessarily inform their health care providers about the consumption of any products other than their conventional medicines. RELEVANCE TO CLINICAL PRACTICE: It is quite essential for health care professionals to be knowledgeable about the use of complementary and alternative medicine therapies when providing medical care to patients with arthritis. PMID- 22776022 TI - In vivo differentiation of human amniotic epithelial cells into cardiomyocyte like cells and cell transplantation effect on myocardial infarction in rats: comparison with cord blood and adipose tissue-derived mesenchymal stem cells. AB - Human amniotic epithelial cells (h-AECs), which have various merits as a cell source for cell therapy, are known to differentiate into cardiomyocytes in vitro. However, the ability of h-AECs to differentiate into cardiomyocytes in vivo and their cell transplantation effects on myocardial infarction are still unknown. In this study, we assessed whether h-AECs could differentiate into cardiomyocytes in vivo and whether h-AECs transplantation can decrease infarct size and improve cardiac function, in comparison to transplantation of cord blood-derived mesenchymal stem cells (MSCs) or adipose tissue-derived MSCs. For our study, we injected h-AECs, cord blood-derived MSCs, adipose tissue-derived MSCs, and saline into areas of myocardial infarction in athymic nude rats. After 4 weeks, 3% of the surviving h-AECs expressed myosin heavy chain, a marker specific to the myocardium. Compared with the saline group, all cell-implanted groups showed a higher ejection fraction, lower infarct area by positron emission tomography and histology, and more abundant myocardial gene and protein expression in the infarct area. We showed that h-AECs can differentiate into cardiomyocyte-like cells, decrease infarct size, and improve cardiac function in vivo. The beneficial effects of h-AECs were comparable to those of cord blood and adipose tissue-derived MSCs. These results support the need for further studies of h-AECs as a cell source for myocardial regeneration due to their plentiful availability, low immunity, and lack of ethical issues related to their use. PMID- 22776024 TI - Histamine in brain development. AB - The function of histamine in the adult central nervous system has been extensively studied, but data on its actions upon the developing nervous system are still scarce. Herein, we review the available information regarding the possible role for histamine in brain development. Some relevant findings are the existence of a transient histaminergic neuronal system during brain development, which includes serotonergic neurons in the midbrain and the rhombencephalon that coexpress histamine; the high levels of histamine found in several areas of the embryo nervous system at the neurogenic stage; the presence of histaminergic fibers and the expression of histamine receptors in various areas of the developing brain; and the neurogenic and proliferative effects on neural stem cells following histamine H(1) - and H(2) -receptor activation, respectively. Altogether, the reviewed information supports a significant role for histamine in brain development and the need for further research in this field. PMID- 22776023 TI - The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by tbx5 deficiency in zebrafish (Danio rerio) embryos. AB - BACKGROUND: Dysmorphogenesis and multiple organ defects are well known in zebrafish (Danio rerio) embryos with T-box transcription factor 5 (tbx5) deficiencies, mimicking human Holt-Oram syndrome. METHODS: Using an oligonucleotide-based microarray analysis to study the expression of special genes in tbx5 morphants, we demonstrated that GH and some GH-related genes were markedly downregulated. Zebrafish embryos microinjected with tbx5-morpholino (MO) antisense RNA and mismatched antisense RNA in the 1-cell stage served as controls, while zebrafish embryos co-injected with exogenous growth hormone (GH) concomitant with tbx5-MO comprised the treatment group. RESULTS: The attenuating effects of GH in tbx5-MO knockdown embryos were quantified and observed at 24, 30, 48, 72, and 96 h post-fertilization. Though the understanding of mechanisms involving GH in the tbx5 functioning complex is limited, exogenous GH supplied to tbx5 knockdown zebrafish embryos is able to enhance the expression of downstream mediators in the GH and insulin-like growth factor (IGF)-1 pathway, including igf1, ghra, and ghrb, and signal transductors (erk1, akt2), and eventually to correct dysmorphogenesis in various organs including the heart and pectoral fins. Supplementary GH also reduced apoptosis as determined by a TUNEL assay and decreased the expression of apoptosis-related genes and proteins (bcl2 and bad) according to semiquantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis, respectively, as well as improving cell cycle related genes (p27 and cdk2) and cardiomyogenetic genes (amhc, vmhc, and cmlc2). CONCLUSIONS: Based on our results, tbx5 knockdown causes a pseudo GH deficiency in zebrafish during early embryonic stages, and supplementation of exogenous GH can partially restore dysmorphogenesis, apoptosis, cell growth inhibition, and abnormal cardiomyogenesis in tbx5 knockdown zebrafish in a paracrine manner. PMID- 22776026 TI - Exploring conflict between caregiving and work for caregivers of elders with dementia: a cross-sectional, correlational study. AB - AIM: To report the moderating effects of work-related conditions and interactive family-care-giving variables, including mutuality and preparedness, on caregiver role strain and mental health for family caregivers of patients with dementia. BACKGROUND: Few studies have examined the interrelationships among caregivers' working conditions, care-giving dynamics and caregiver well-being. DESIGN: Cross sectional, correlational study. METHODS: Data were collected by self-completed questionnaires from 176 primary family caregivers of patients with dementia in Taiwan from May 2005-January 2006. Caregiver role strain and mental health were analysed by multiple regressions using a hierarchical method to enter independent variables and two- and three-way interaction terms after controlling for caregiver age and gender, employment status, and work flexibility and the simple effect of each independent variable. RESULTS: More preparedness was associated with less role strain for family caregivers with less work/care-giving conflict. More care-giving demand was associated with poorer mental health only for caregivers with low work/care-giving conflict and with average and low preparedness, but not high preparedness. For family caregivers with less work/care-giving conflict, more preparedness decreased role strain and maintained mental health even when care-giving demand was high. CONCLUSION: These results provide a knowledge base for understanding complex family caregiver phenomena and serve as a guide for developing interventions. Future studies with longitudinal follow-ups are suggested to explore actual causal relationships. PMID- 22776025 TI - Calpastatin overexpression protects axonal transport in an in vivo model of traumatic axonal injury. AB - Traumatic brain injury (TBI) causes substantial morbidity and mortality worldwide. A key component of both mild and severe TBI is diffuse axonal injury. Except in cases of extreme mechanical strain, when axons are torn at the moment of trauma, axonal stretch injury is characterized by early cytoskeletal proteolysis, transport disruption, and secondary axotomy. Calpains, a family of Ca(2+)-dependent proteases, have been implicated in this pathologic cascade, but direct in vivo evidence is lacking. To test the hypothesis that calpains play a causal role in axonal stretch injury in vivo, we used our rat optic nerve stretch model following adeno-associated viral (AAV) vector-mediated overexpression of the endogenous calpain inhibitor calpastatin in optic nerve axons. AAV vectors were designed for optimal expression of human calpastatin (hCAST) in retinal ganglion cells (RGCs). Calpain inhibition by the expressed protein was then confirmed in primary cortical cultures. Finally, we performed bilateral intravitreal injections of AAV vectors expressing hCAST or the reporter protein ZsGreen 3 weeks prior to unilateral optic nerve stretch. Immediately after stretch injury, Fluoro-Gold was injected into the superior colliculi for assessment of retrograde axonal transport. Rats were euthanized 4 days after stretch injury. Both hCAST and ZsGreen were detected in axons throughout the optic nerve to the chiasm. Calpastatin overexpression partially preserved axonal transport after stretch injury (58.3+/-15.6% reduction in Fluoro-Gold labeling relative to uninjured contralateral controls in ZsGreen-expressing RGCs, versus 33.8+/-23.9% in hCAST-expressing RGCs; p=0.038). These results provide direct evidence that axonal calpains play a causal role in transport disruption after in vivo stretch injury. PMID- 22776027 TI - Testosterone deficiency in male heart failure patients and its effect on endothelial progenitor cells. AB - BACKGROUND: Endothelial progenitor cells (EPCs) are thought to contribute to reendothelialization and neoangiogenesis. Since it is known that EPCs express a testosterone receptor, we wanted to assess the prevalence of testosterone deficiency in patients with CHF and its impact on circulating EPCs. METHODS: 137 male patients with chronic heart failure (CHF) were included (age 61 +/- 13 years; BMI 29 +/- 5 kg/m(2); New York Heart Association classification (NYHA) I: n = 47, NYHA II: n = 51, NYHA III: n = 39). Numbers of different populations of circulating EPCs were quantified using flow cytometry. Levels of free testosterone and EPC-regulating cytokines were determined using ELISA. RESULTS: The prevalence of testosterone deficiency in our University CHF clinic was 39%. However, there was no difference between patients with and without testosterone deficiency regarding their levels of EPCs. Testosterone levels were inversely correlated with age (R(2) = -0.32, p = 0.001) and NYHA status (R(2) = 0.28, p = 0.001) and correlated with cardiorespiratory capacity (R(2) = 0.26, p = 0.03). CONCLUSION: Testosterone deficiency is frequent in male patients with CHF but does not appear to impact the regenerative EPCs. PMID- 22776028 TI - Does assisted reproductive treatment increase the risk of birth defects in the offspring? PMID- 22776029 TI - Variation in the level of aggression, chemical and genetic distance among three supercolonies of the Argentine ant in Europe. AB - In their invasive ranges, Argentine ant populations often form one geographically vast supercolony, genetically and chemically uniform within which there is no intraspecific aggression. Here we present regional patterns of intraspecific aggression, cuticular hydrocarbons (CHCs) and population genetics of 18 nesting sites across Corsica and the French mainland. Aggression tests confirm the presence of a third European supercolony, the Corsican supercolony, which exhibits moderate to high levels of aggression, depending on nesting sites, with the Main supercolony, and invariably high levels of aggression with the Catalonian supercolony. The chemical analyses corroborated the behavioural data, with workers of the Corsican supercolony showing moderate differences in CHCs compared to workers of the European Main supercolony and strong differences compared to workers of the Catalonian supercolony. Interestingly, there were also clear genetic differences between workers of the Catalonian supercolony and the two other supercolonies at both nuclear and mitochondrial markers, but only very weak genetic differentiation between nesting sites of the Corsican and Main supercolonies (F(ST) = 0.06). A detailed comparison of the genetic composition of supercolonies also revealed that, if one of the last two supercolonies derived from the other, it is the Main supercolony that derived from the Corsican supercolony rather than the reverse. Overall, these findings highlight the importance of conducting more qualitative and quantitative analyses of the level of aggression between supercolonies, which has to be correlated with genetic and chemical data. PMID- 22776030 TI - Associations between spousal or significant other solicitous responses and opioid dose in patients with chronic pain. AB - OBJECTIVE: The primary aim of this study was to determine the effects of spouse or significant other solicitous responses on morphine equivalent dose among adults with chronic pain. DESIGN: Retrospective design. SETTING: Multidisciplinary pain rehabilitation center. PATIENTS: The cohort included 466 consecutively admitted patients who had a spouse or significant other and were using daily opioids. Intervention. Three-week outpatient pain rehabilitation program. OUTCOME MEASURES: Solicitous subscale of the Multidimensional Pain Inventory and morphine equivalent dose upon admission. RESULTS: The mean solicitous subscale score and morphine equivalent dose were 49.8 (standard deviation [SD] = 8.7) and 118mg/day (SD =149), respectively. Univariate linear regression analysis showed that greater subscale scores were associated with greater doses of opioids (P = 0.007). In a multivariate model adjusted for age, sex, ethnicity, years of education, employment status, pain duration, depression, and pain severity, the association retained significance (P = 0.007). CONCLUSIONS: These findings suggest solicitous responses from a spouse or significant other may have an important influence on opioid dose among adults with chronic pain. PMID- 22776031 TI - Commentary on a GWAS: HDAC9 and the risk for ischaemic stroke. AB - Modifiable risk factors like obesity, hypertension, smoking, physical inactivity or atrial fibrillation account for a significant proportion of the risk for ischaemic stroke, but genetic variation is also believed to contribute to the risk, although few genetic risk variants were identified to date. Common clinical subtypes of stroke are caused by cardiac embolism, large artery atherosclerosis and small cerebral vessel disease. Each of these underlying pathologies may have a specific genetic architecture.Previous genome-wide association studies (GWAS) showed association of variants near PITX2 and ZFHX3 with atrial fibrillation and stroke. ANRIL (antisense Non-coding RNA in the INK4 Locus (harboring the CDKN2A/B genes)) variants were related to a variety of vascular diseases (myocardial infarction, aortic and intracranial aneurysm), including ischaemic stroke. Now a recent GWAS published in Nature Genetics confirmed these previous associations, analyzed the specificity of the previous associations with particular stroke subtypes and identified a new association between HDAC9 and large vessel stroke. The findings suggest that well-recognized clinical stroke subtypes correspond to distinct aetiological entities. However, the molecular pathways that are affected by the identified genetic variants are not yet pinpointed, and the observed associations apply only for some, but not all victims of a specific stroke aetiology. PMID- 22776032 TI - Use new PLGL-RGD-NGF nerve conduits for promoting peripheral nerve regeneration. AB - BACKGROUND: Nerve conduits provide a promising strategy for peripheral nerve injury repair. However, the efficiency of nerve conduits to enhance nerve regeneration and functional recovery is often inferior to that of autografts. Nerve conduits require additional factors such as cell adhesion molecules and neurotrophic factors to provide a more conducive microenvironment for nerve regeneration. METHODS: In the present study, poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} (PLGL) was modified by grafting Gly-Arg-Gly-Asp-Gly (RGD peptide) and nerve growth factor (NGF) for fabricating new PLGL-RGD-NGF nerve conduits to promote nerve regeneration and functional recovery. PLGL-RGD-NGF nerve conduits were tested in the rat sciatic nerve transection model. Rat sciatic nerves were cut off to form a 10 mm defect and repaired with the nerve conduits. All of the 32 Wistar rats were randomly divided into 4 groups: group PLGL-RGD-NGF, group PLGL-RGD, group PLGL and group autograft. At 3 months after surgery, the regenerated rat sciatic nerve was evaluated by footprint analysis, electrophysiology, and histologic assessment. Experimental data were processed using the statistical software SPSS 10.0. RESULTS: The sciatic function index value of groups PLGL-RGD-NGF and autograft was significantly higher than those of groups PLGL-RGD and PLGL. The nerve conduction velocities of groups PLGL-RGD-NGF and autograft were significantly faster than those of groups PLGL-RGD and PLGL. The regenerated nerves of groups PLGL-RGD-NGF and autograft were more mature than those of groups PLGL-RGD and PLGL. There was no significant difference between groups PLGL-RGD-NGF and autograft. CONCLUSIONS: PLGL-RGD-NGF nerve conduits are more effective in regenerating nerves than both PLGL-RGD nerve conduits and PLGL nerve conduits. The effect is as good as that of an autograft. This work established the platform for further development of the use of PLGL-RGD-NGF nerve conduits for clinical nerve repair. PMID- 22776033 TI - Rapid genetic targeting of pial surface neural progenitors and immature neurons by neonatal electroporation. AB - BACKGROUND: Recent findings have indicated the presence of a progenitor domain at the marginal zone/layer 1 of the cerebral cortex, and it has been suggested that these progenitors have neurogenic and gliogenic potential. However, their contribution to the histogenesis of the cortex remains poorly understood due to difficulties associated with genetically manipulating these unique cells in a population-specific manner. RESULTS: We have adapted the electroporation technique to target pial surface cells for rapid genetic manipulation at postnatal day 2. In vivo data show that most of these cells proliferate and progressively differentiate into both neuronal and glial subtypes. Furthermore, these cells localize to the superficial layers of the optic tectum and cerebral cortex prior to migration away from the surface. CONCLUSIONS: We provide a foundation upon which future studies can begin to elucidate the molecular controls governing neural progenitor fate, migration, differentiation, and contribution to cortical and tectal histogenesis. Furthermore, specific genetic targeting of such neural progenitor populations will likely be of future clinical interest. PMID- 22776034 TI - Visceral analgesia induced by acute and repeated water avoidance stress in rats: sex difference in opioid involvement. AB - BACKGROUND: Chronic psychological stress-induced alterations in visceral sensitivity have been predominantly assessed in male rodents. We investigated the effect of acute and repeated water avoidance stress (WAS) on the visceromotor response (VMR) to colorectal distension (CRD) and the role of opioids in male and cycling female Wistar rats using a novel non-invasive manometric technique. METHODS: After a baseline VMR (1st CRD, day 0), rats were exposed to WAS (1 h day(-1) ) either once or for four consecutive days, without injection or with naloxone (1 mg kg(-1) ) or saline injected subcutaneously before each WAS session. KEY RESULTS: The VMR to CRD recorded on day 1 or 4 immediately after the last WAS was reduced in both females and males. The visceral analgesia was mainly naloxone-dependent in females, but naloxone-independent in males. In non-injected animals, on days 2 and 5, VMR was not significantly different from baseline in males whereas females exhibited a significant VMR increase at 60 mmHg on day 5. Basal CRD and CRD on days 1, 2, and 5 in both sexes without WAS induced similar VMR. CONCLUSIONS & INFERENCES: When monitored non-invasively, psychological stress induces an immediate poststress visceral analgesia mediated by an opiate signaling system in females while naloxone-independent in males, and hyperalgesia at 24 h after repeated stress only in females. These data highlight the importance of sex-specific interventions to modulate visceral pain response to stress. PMID- 22776035 TI - Protective effects of salidroside from Rhodiola rosea on LPS-induced acute lung injury in mice. AB - Salidroside is a major component extracted from Rhodiola rosea. In this study, we investigated protective effects of salidroside on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice. In the mouse model, we found that pretreatment with a single 120 mg/kg dose of salidroside prior to the administration of intratracheal LPS induced a significant decrease in the W/D ratio and mouse myeloperoxidase activity of lung, reduction protein concentration, the number of total cells, neutrophils and macrophages in the bronchoalveolar lavage fluid. In addition, salidroside also inhibited the production of several inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6 (IL-6) and IL-1beta, and the NF-kappaB DNA-binding activation after LPS challenge. These results indicated that salidroside possess a protective effect on LPS-induced ALI in mice. PMID- 22776037 TI - Evaluating the effect of disturbed ensemble distributions on SCFG based statistical sampling of RNA secondary structures. AB - BACKGROUND: Over the past years, statistical and Bayesian approaches have become increasingly appreciated to address the long-standing problem of computational RNA structure prediction. Recently, a novel probabilistic method for the prediction of RNA secondary structures from a single sequence has been studied which is based on generating statistically representative and reproducible samples of the entire ensemble of feasible structures for a particular input sequence. This method samples the possible foldings from a distribution implied by a sophisticated (traditional or length-dependent) stochastic context-free grammar (SCFG) that mirrors the standard thermodynamic model applied in modern physics-based prediction algorithms. Specifically, that grammar represents an exact probabilistic counterpart to the energy model underlying the Sfold software, which employs a sampling extension of the partition function (PF) approach to produce statistically representative subsets of the Boltzmann weighted ensemble. Although both sampling approaches have the same worst-case time and space complexities, it has been indicated that they differ in performance (both with respect to prediction accuracy and quality of generated samples), where neither of these two competing approaches generally outperforms the other. RESULTS: In this work, we will consider the SCFG based approach in order to perform an analysis on how the quality of generated sample sets and the corresponding prediction accuracy changes when different degrees of disturbances are incorporated into the needed sampling probabilities. This is motivated by the fact that if the results prove to be resistant to large errors on the distinct sampling probabilities (compared to the exact ones), then it will be an indication that these probabilities do not need to be computed exactly, but it may be sufficient and more efficient to approximate them. Thus, it might then be possible to decrease the worst-case time requirements of such an SCFG based sampling method without significant accuracy losses. If, on the other hand, the quality of sampled structures can be observed to strongly react to slight disturbances, there is little hope for improving the complexity by heuristic procedures. We hence provide a reliable test for the hypothesis that a heuristic method could be implemented to improve the time scaling of RNA secondary structure prediction in the worst-case - without sacrificing much of the accuracy of the results. CONCLUSIONS: Our experiments indicate that absolute errors generally lead to the generation of useless sample sets, whereas relative errors seem to have only small negative impact on both the predictive accuracy and the overall quality of resulting structure samples. Based on these observations, we present some useful ideas for developing a time-reduced sampling method guaranteeing an acceptable predictive accuracy. We also discuss some inherent drawbacks that arise in the context of approximation. The key results of this paper are crucial for the design of an efficient and competitive heuristic prediction method based on the increasingly accepted and attractive statistical sampling approach. This has indeed been indicated by the construction of prototype algorithms. PMID- 22776036 TI - Prevalence, determinants and co-morbidities of chronic kidney disease among First Nations adults with diabetes: results from the CIRCLE study. AB - BACKGROUND: Indigenous peoples worldwide are experiencing elevated rates of type 2 diabetes and its complications. To better understand the disproportionate burden of diabetic end stage renal disease (ESRD) among Canadian First Nations people (FN), we examined prevalence, determinants, and co-morbidities of chronic kidney disease (CKD) within this population. METHODS: The 2007 Canadian FN Diabetes Clinical Management and Epidemiologic (CIRCLE) study conducted a cross sectional national medical chart audit of 885 FN adults with type 2 diabetes to assess quality of diabetes care. In this sub-study, participants were divided by estimated glomerular filtration rate (eGFR in ml/min/1.73 m2), as well as by albuminuria level in those with eGFRs = > 60. Those with eGFRs = > 60 and negative albuminuria were considered to have normal/near normal kidney function (non-CKD). Using univariate and logistic regression analysis, they were compared with participants having eGFRs = > 60 plus albuminuria (CKD-alb) and with participants having eGFRs <60 (CKD-eGFR <60). RESULTS: While 84.5% of total CIRCLE participants had eGFRs = > 60, almost 60% of the latter had CKD-alb. Of the 15.5% of total participants with CKD-eGFR <60, 80% had eGFRs 30-60 (Stage 3 CKD) but over 10% (1.6% of total participants) had ESRD. Independent determinants of CKD-alb were male gender and increasing diabetes duration, systolic BP, A1C and total cholesterol. These plus smoking rates also discriminated between FN with micro- and macro-albuminuria. Independent determinants of CKD-eGFR <60 were increasing age at diabetes diagnosis, diabetes duration, total cholesterol and systolic BP. However, participants with CKD-eGFR <60 also displayed a decreasing mean age of diabetes diagnosis as eGFR declined. Micro-vascular co-morbidities were significantly associated with CKD-alb but both micro- and macro-vascular co morbidities were associated with CKD-eGFR <60. Only 35-40% of participants with CKD used insulin. CONCLUSIONS: High prevalences of CKD-alb and early CKD-eGFR <60 among diabetic FN were largely related to modifiable and treatable risk factors. However, an earlier age of diabetes diagnosis and longer duration of diabetes characterized those with ESRD. These findings suggest that a failure to meet current standards of diabetes care interacting with an age-related survival benefit contribute to the disproportionate burden of ESRD among FN and possibly other Indigenous peoples. PMID- 22776038 TI - Prevalence of sinonasal outcome test (SNOT-22) symptoms in patients undergoing surgery for chronic rhinosinusitis in the England and Wales National prospective audit. AB - OBJECTIVES: Review and evaluate the prevalence and severity of individual symptoms in patients with chronic rhinosinusitis (CRS) with or without nasal polyposis. DESIGN AND SETTING: Retrospective analysis of data from the National Comparative Audit of Surgery for Nasal Polyposis and CRS, carried out across 87 hospitals in England and Wales between 2000 and 2001. PARTICIPANTS: A total of 2573 patients with CRS (1784 had CRS with nasal polyposis, 789 without nasal polyposis) who had undergone sinus surgery. MAIN OUTCOME MEASURES: Severity of clinical symptoms scores was graded on the Sino-Nasal Outcome Test 22 questionnaire. Prevalence of these symptoms and mean symptom scores were calculated for each group of patients at baseline and 3 months after surgery. RESULTS: In both groups, nasal blockage/congestion had the highest mean symptom score, followed by altered smell/taste and then the need to blow nose. These three symptoms were the most prevalent in the group with nasal polyposis. In the group without nasal polyposis, nasal blockage was also the most prevalent individual symptom (93.5%) followed by altered smell/taste (75.7%). The third most prevalent symptom was waking up tired (69.9%). The average test score preoperatively was 41.5 (group with nasal polyposis) and 44.4 (group without nasal polyposis). This decreased to 18.3 and 14.1, respectively, 3 months after surgery (P < 0.001). CONCLUSION: The leading three symptoms were nasal blockage/congestion, altered taste/smell and the need to blow the nose in terms of severity and prevalence. The total Sino-Nasal Outcome Test 22 and all individual symptom scores improved significantly after surgery. PMID- 22776040 TI - Utilization of vinasse for production of poly-3-(hydroxybutyrate-co hydroxyvalerate) by Haloferax mediterranei. AB - Vinasse, a highly polluting waste of the ethanol industry was utilized for the production of polyhydroxyalkanoate (PHA) by the extremely halophilic archaeon, Haloferax mediterranei in shake-flasks. Following pre-treatment through adsorption on activated carbon, 25%-50% (v/v) pre-treated vinasse was utilized leading to 70% maximum accumulation of PHA. Maximum PHA concentration of 19.7 g/l, product yield coefficient (based on total carbohydrates) of 0.87 and 0.21 g/l h volumetric productivity were achieved. Concomitant lowering of BOD5 of pre treated vinasse by at least 78% and COD by at least 80% was attained at the end of this process. The PHA was recovered by osmotic lysis of the cells and purification by sodium hypochlorite and organic solvents. Through UV-vis spectroscopy, gas chromatography, differential scanning calorimetry and nuclear magnetic resonance spectroscopy, the PHA was identified as poly-3 (hydroxybutyrate-co-hydroxyvalerate). The 3-hydroxyvalerate content was 12.36 mol % (utilizing 25% pre-treated vinasse) and 14.09 mol % (utilizing 50% pre-treated vinasse). High salt concentration in the medium allowed this process without sterile conditions and thus reduction in costs of sterilization can be envisaged. Activated charcoal pre-treatment of vinasse is economical than competing processes such as ultrafiltration of whey, extrusion and enzymatic treatment of rice and corn starch. Without impacting sugar prices, this process can easily be integrated into a distillery that has fermentation equipment and trained personnel. High PHA content, productivity, zero-cost carbon source, low-cost isolation of a high-purity product and potential integration into ethanol manufacturing unit with concomitant wastewater treatment should merit further development of this process to higher scales. PMID- 22776041 TI - Ions, equations and electrons: the evolving role of computer simulations in cardiac electrophysiology safety evaluations. AB - Reliable preclinical cardiac safety evaluations of drug candidates are essential for selecting the best therapeutic agents. Advanced automated patch clamp technologies now allow for characterizing drug effects on multiple cardiac currents, enabling subsequent simulations of integrated electrophysiological responses on cellular, tissue and organ levels. In this issue, Mirams et al. summarize the strengths and limitations of models and simulations predicting drug induced electrophysiological responses, emphasizing delayed repolarization and Torsades de Pointes pro-arrhythmia. The utility of computational approaches is contingent upon realistic models of ventricular electrophysiology, robust characterization of drug-channel interactions and an understanding of channel myocyte interactions and pro-arrhythmic mechanisms. Simulations evaluating effects on repolarization (hazard identification) should aid in selecting safer drug candidates early in drug discovery, while simulations evaluating risk of Torsades de Pointes (incorporating known risk factors) should quantify pro arrhythmic risk and reduce the need for costly clinical QT studies later in development. The wider adoption of realistic models and simulation studies will depend on simulation performance compared with 'gold standard' clinical findings. PMID- 22776039 TI - GLP-1 receptor activated insulin secretion from pancreatic beta-cells: mechanism and glucose dependence. AB - The major goal in the treatment of type 2 diabetes mellitus is to control the hyperglycaemia characteristic of the disease. However, treatment with common therapies such as insulin or insulinotrophic sulphonylureas (SU), while effective in reducing hyperglycaemia, may impose a greater risk of hypoglycaemia, as neither therapy is self-regulated by ambient blood glucose concentrations. Hypoglycaemia has been associated with adverse physical and psychological outcomes and may contribute to negative cardiovascular events; hence minimization of hypoglycaemia risk is clinically advantageous. Stimulation of insulin secretion from pancreatic beta-cells by glucagon-like peptide 1 receptor (GLP-1R) agonists is known to be glucose-dependent. GLP-1R agonists potentiate glucose stimulated insulin secretion and have little or no activity on insulin secretion in the absence of elevated blood glucose concentrations. This 'glucose-regulated' activity of GLP-1R agonists makes them useful and potentially safer therapeutics for overall glucose control compared to non-regulated therapies; hyperglycaemia can be reduced with minimal hypoglycaemia. While the inherent mechanism of action of GLP-1R agonists mediates their glucose dependence, studies in rats suggest that SUs may uncouple this dependence. This hypothesis is supported by clinical studies showing that the majority of events of hypoglycaemia in patients treated with GLP-1R agonists occur in patients treated with a concomitant SU. This review aims to discuss the current understanding of the mechanisms by which GLP-1R signalling promotes insulin secretion from pancreatic beta-cells via a glucose dependent process. PMID- 22776042 TI - Lymphatic space invasion is not an independent predictor of outcomes in early stage breast cancer treated by breast-conserving surgery and radiation. AB - To study the prognostic importance of lymphovascular invasion (LVI) in early stage breast cancer after conservative surgery and radiation. From 2/80 to 8/07, 1,478 patients were treated with breast-conserving surgery and radiation with or without systemic therapy. Study eligibility included breast conservation, whole breast postoperative radiation, T1-T2 disease, and known LVI status. Endpoints were 5- and 10-year actuarial outcomes for local control and survival. LVI was present in 427 patients and absent in 1,051 patients. Median follow-up was 68 and 69 months, respectively. Patients with LVI had a younger median age, were more often pre- or perimenopausal, T2, physically palpable, invasive ductal, node positive, grade 3, and treated with chemotherapy compared with patients without LVI. The 5- and 10-year local-regional recurrence was 4.5% and 9.6% with LVI compared with 1.6% and 5.6% without LVI (p = 0.01). The 5- and 10-year overall survival was 83% and 68% for LVI and 91% and 80% for no LVI, respectively (p < 0.0001). Multivariate analysis showed that LVI was not an independent predictor of local-regional control (p = 0.0697) or survival (p = 0.1184). LVI in breast cancer is found in association with other worse prognostic factors for outcome, is associated with a modest increase in local-regional recurrence, but is not an independent predictor of local-regional recurrence or survival on multivariate analysis. PMID- 22776043 TI - Health comorbidities and cognition in 1948 patients with idiopathic Parkinson's disease. AB - BACKGROUND: Health comorbidities, particularly cardiovascular factors, are well known to pose risks for cognitive decline in older adults. This study examined the prevalence and contribution of comorbidities on cognitive performance in a large cohort of Parkinson patients. METHODS: Data on 1948 PD patients were obtained from the National Parkinson Foundation Quality Improvement Initiative (NPF-QII) registry, a multi-site initiative from NPF Centers of Excellence. Available comorbidity data included six common conditions (heart/circulation problems, diabetes, arthritis, cancer, respiratory disease, and other neurologic disease) that were clinician-rated for presence and severity. Available cognitive measures included semantic fluency and a 5-word recall memory task. The unique effects of comorbidities on cognition were analyzed (multiple hierarchical regression) controlling for demographic, PD disease severity (duration, Hoehn Yahr), and medication status. RESULTS: The two most reported comorbidities were arthritis (46.6%) and heart/circulation problems (36.3%), with diabetes affecting 9% of the sample. Severity of heart/circulation problems independently contributed to worse delayed recall performance (p = 0.03). A trend emerged for more severe diabetes as contributing to worse semantic fluency scores (p = 0.06). CONCLUSIONS: This study with a large cohort of PD patients provides evidence for a small detrimental influence of specific health comorbidities, particularly heart/circulatory and diabetes, on general measures of cognition. This effect is present, above and beyond the influences of basic demographic information (age), duration and staging of PD, and medication status. Future studies involving more refined cognitive indices and direct assessment of comorbidities are warranted. PMID- 22776044 TI - What are the issues facing Parkinson's disease patients at ten years of disease and beyond? Data from the NPF-QII study. AB - BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative syndrome, classically characterized by levodopa-responsive motor features accompanied by non-motor mood, cognitive, sensory and autonomic issues. Over time, disease burden slowly accumulates resulting in diminished health status. Many clinicians consider the 10 year disease duration mark as significant, however the clinical status and health-related quality of life of patients reaching this milestone have not been well documented. METHODS: A cross-sectional study was performed on PD patients with >= 10 years disease duration (PD-10) (n = 1835) included in the multicenter National Parkinson's Foundation Quality Improvement Initiative (NPF-QII). Demographic, clinical and health-related quality of life data was analyzed. RESULTS: PD-10 patients (62.2% male) had a mean age of 67.8 years (+/- 9.5) with a mean age of PD onset of 52.7 years (+/- 10.6), and median disease duration 14.3 years (interquartile range 11.5-18.1). Many were minimally disabled with Hoehn and Yahr stage 1 or 2 (44.0%) or experiencing postural instability (HY stage 3, 40.3%). Most (88.2%) were able to stand unaided, but falls were common (54.8%). Almost all were living at home (93.1%) with a family member as a regular caregiver (83.8%). PD-10 patients had an average of 1.9 (+/- 1.4) co-morbidities, with arthritis (48.9%) and heart problems (31.7%) most commonly encountered. The majority (86.7%) took at least 2 medications: levodopa (95.7%), dopamine agonists (45.6%) and antidepressants (37.3%) were most commonly recorded. Most PD-10 patients were not currently utilizing physical, occupational or speech therapy, although two-thirds reported engaging in physical activity. Deep brain stimulation was documented in 22.4%. Overall the mean health-related quality of life and caregiver burden was impaired in all domains. CONCLUSIONS: Our data on PD patients with at least 10 years disease duration confirmed the younger age of onset of PD, but not the higher proportion of females or rest tremor, or the lower proportion of Caucasians seen in other aged PD cohorts. PD-10 patients had increased disease burden, increased caregiver burden, and impaired health-related quality of life. Although subjects mostly remained independently mobile, balance could be impaired with frequent falls identified. The prevalence of PD-10 patients living at home (93%) was very high in our sample which was drawn from specialty clinics, compared to prior studies reporting up to 27% PD patients institutionalized at 10 years duration. Thus policies to improve in-home support and caregiver support will be crucial in efforts aimed at maintaining patients in a home setting. PMID- 22776045 TI - Carbohydrate counting with a bolus calculator improves post-prandial blood glucose levels in children and adolescents with type 1 diabetes using insulin pumps. AB - AIM: Carbohydrate counting (CC) is widely used in insulin pumps. The primary objectives of this study were improvement of HbA1c and meal-related plasma glucose (PG) levels when using CC. METHODS: Forty patients with pump treatment, aged 13.8 +/- 3.4 yr (range 5.0-19.5) and diabetes duration 8.0 +/- 3.8 (1.8 16.8) years completed a 1-yr multi-center study. HbA1c at start was 7.6 +/- 0.9% Diabetes Control and Complications Trial (DCCT), 59 +/- 10 mmol/mol International Federation for Clinical Chemistry and Laboratory Medicine (IFCC). They were randomized into (A) control group, (B) manual CC, and (C) CC with a bolus calculator in the pump for calculations. (B) and (C) received education in CC while (A) received equal hours of traditional dietary education. Glucose meters were downloaded at visits and the standard deviation (PG-SD) calculated. PG measurements from before and 2 h after meals were registered separately. RESULTS: We found no difference in HbA1c between the groups. Group C had a non-significant decrease in PG-SD (p = 0.056) compared to start, and a significantly higher number of post-meal PG between 4 and 8 mmol/L at 12 months compared to group A (55.3% vs. 30.6%, p = 0.014). The frequency of hypoglycemia was reduced for the whole study group (p = 0.01), but with no significant difference between groups. (A) significantly increased their basal-insulin dosage at 12 months. In (C), all subjects wanted to continue CC after the study. The insulin:carbohydrate ratio correlated significantly to the insulin-dose/24 h (p = 0.003) and the correction factor to the insulin-dose/24 h (p = 0.035) and age (p < 0.001). CONCLUSIONS: We conclude that CC using a bolus calculator may help decrease PG-fluctuations and increase post-meal PG values within target. PMID- 22776047 TI - Opinions on the preclinical evaluation of novel therapies for spinal cord injury: a comparison between researchers and spinal cord-injured individuals. AB - We previously conducted a survey to gather the opinions and perspectives of scientific and clinical researchers on what levels of preclinical evidence were needed to justify translating a promising neuroprotective or neuroregenerative therapy in spinal cord injury (SCI) into a human clinical trial (Kwon et al., 2010 ). Here we conducted an analogous survey of individuals living with SCI in which we gathered their expectations for the levels of preclinical evidence achieved by researchers in substantiating the neuroprotective and neuroregenerative therapies being offered to them in clinical trials. In total, 214 individuals with SCI completed the survey, and their responses were compared to the responses of the 235 scientists and clinicians who completed our previous survey. SCI individuals were more likely than SCI researchers to opine that demonstrating efficacy and safety in rodent models of SCI alone is sufficient to proceed with clinical trials. However, SCI individuals also reported strong support for large animal and primate model studies, and in the case of the latter, were actually more in agreement for the need for primate studies than researchers. SCI individuals also reported strong support for independent replication studies. In general, individuals with SCI had high expectations for the levels of preclinical evidence required to justify translating novel therapies into clinical trials. These expectations should be considered in the decisions to translate specific experimental therapies for SCI. PMID- 22776046 TI - Chronic exposure to corticosterone enhances the neuroinflammatory and neurotoxic responses to methamphetamine. AB - Up-regulation of proinflammatory cytokines and chemokines in brain ("neuroinflammation") accompanies neurological disease and neurotoxicity. Previously, we documented a striatal neuroinflammatory response to acute administration of a neurotoxic dose of methamphetamine (METH), i.e. one associated with evidence of dopaminergic terminal damage and activation of microglia and astroglia. When we used minocycline to suppress METH-induced neuroinflammation, indices of dopaminergic neurotoxicity were not affected, but suppression of neuroinflammation was incomplete. Here, we administered the classic anti-inflammatory glucocorticoid, corticosterone (CORT), in an attempt to completely suppress METH-related neuroinflammation. METH alone caused large increases in striatal proinflammatory cytokine/chemokine mRNA and subsequent astrocytic hypertrophy, microglial activation, and dopaminergic nerve terminal damage. Pre-treatment of mice with acute CORT failed to prevent neuroinflammatory responses to METH. Surprisingly, when mice were pre-treated with chronic CORT in the drinking water, an enhanced striatal neuroinflammatory response to METH was observed, an effect that was accompanied by enhanced METH-induced astrogliosis and dopaminergic neurotoxicity. Chronic CORT pre-treatment also sensitized frontal cortex and hippocampus to mount a neuroinflammatory response to METH. Because the levels of chronic CORT used are associated with high physiological stress, our data suggest that chronic CORT therapy or sustained physiological stress may sensitize the neuroinflammatory and neurotoxicity responses to METH. PMID- 22776048 TI - Ulcerative dermatitis in C57BL/6 mice exhibits an oxidative stress response consistent with normal wound healing. AB - Ulcerative dermatitis (UD) is a common syndrome of unknown etiology that results in profound morbidity in C57BL/6 mice and lines on a C57BL/6 background. The lesions are due to severe pruritus-induced self-trauma, progressing from superficial excoriations to deep ulcerations. UD may be behavioral in origin, with ulcerative lesions resulting from self-mutilating behavior in response to unresolved inflammation or compulsion. Alternatively, abnormal oxidative damage may be a mechanism underlying UD. To evaluate whether UD behaves similarly to normal wounds, consistent with a secondary self-inflicted lesion, or is a distinct disorder with abnormal wound response, we evaluated expression levels of genes representing various arms of the oxidative stress response pathway UD affected and unwounded C57BL/6J mice. No evidence indicated that UD wounds have a defect in the oxidative stress response. Our findings are consistent with an understanding of C57BL/6 UD lesions as typical rather than atypical wounds. PMID- 22776049 TI - Markers for heightened monitoring, imminent death, and euthanasia in aged inbred mice. AB - The goal of this study was to identify objective criteria that would reliably predict spontaneous death in aged inbred mice. We evaluated male and female AKR/J mice, which die at a relatively young age due to the development of lymphoma, as well as male C57BL/6J and BALB/cByJ mice. Mice were implanted subcutaneously with an identification chip that also allowed remote measurement of body temperature. Temperatures and body weights were measured weekly until spontaneous death occurred or until euthanasia was performed for humane reasons. In AKR/J mice, hypothermia and weight loss began about 4 wk prior to death and increased gradually during that antemortem interval. In C57BL/6J and BALB/cByJ mice, these declines began earlier and were more prolonged prior to death. However, C57BL/6J and BALB/cByJ mice developed a relatively precipitous hypothermia during the 2 wk prior to death. For all 3 strains, the derived composite score of temperature * weight, expressed as a percentage of stable values for each mouse, was similarly informative. These changes in individual and composite measures can signal the need for closer observation or euthanasia of individual mice. Validated markers of clinical decline or imminent death can allow the use of endpoints that reduce terminal distress, do not significantly affect longevity or survival data, and permit timely collection of biologic samples. PMID- 22776050 TI - Expression of maspin in the early pregnant mouse endometrium and its role during embryonic implantation. AB - Maspin (serpin B5), a tumor-suppressing member of the serine protease inhibitor family, participates in cell migration, adhesion, invasion, and apoptosis. These processes are also critical for embryo implantation, but the role of maspin in embryo implantation remains poorly understood. The aim of the present study was to investigate the spatiotemporal expression of maspin in early pregnant mouse endometrium and its role in embryo implantation. Real-time quantitative PCR analysis, immunohistochemistry, and Western blotting were used to detect mRNA and protein expression of maspin in the endometria of nonpregnant and early pregnant (days 0 to 7) mice. On day 3 of pregnancy, mice in the treated group (n = 20) were injected in the left uterine horn with antimaspin polyclonal antibody and in the right horn with purified rabbit IgG; control mice (n = 20) were injected only with purified rabbit IgG in the right uterine horn. Implanted embryos were counted on pregnant day 8. The mRNA and protein expressions of maspin were higher in the endometria of pregnant mice than nonpregnant mice; these levels gradually increased from day 1 of pregnancy, peaked on day 5, and then decreased on days 6 and 7. The mice treated with antimaspin polyclonal antibody group had far fewer implanted embryos than did the control group. Taken together, these results suggest that maspin, a tumor suppressor, may play an important role in embryo implantation. PMID- 22776051 TI - Genomic analysis and pathogenic characteristics of lymphocytic choriomeningitis virus strains isolated in Japan. AB - Lymphocytic choriomeningitis virus (LCMV) is a zoonotic pathogen of which mice are the natural reservoir. Different strains and clones of LCMV show different pathogenicity in mice. Here we determined the complete genomic sequences of 3 LCMV strains (OQ28 and BRC which were isolated from mice in Japan and WE(ngs) which was derived from strain WE). Strains OQ28 and BRC showed high sequence homology with other LCMV strains. Although phylogenetic analyses placed these 2 Japanese strains in different subclusters, they belonged to same cluster of LCMV isolates. WE(ngs) and WE had many sequence substitutions between them but fell into same subcluster. The pathogenicity of the 3 new LCMV isolates was examined by inoculating ICR mice with 102 and 104 TCID50 of virus. ICR mice infected with OQ28 or WE(ngs) exhibited severe clinical signs, and some of the infected mice died. In contrast, all ICR mice infected with BRC showed no clinical signs and survived infection. Virus was detected in the blood, organs, or both of most of the surviving ICR mice inoculated with either OQ28 or WE(ngs). However, virus was below the level of detection in all ICR mice surviving infection with strain BRC. Therefore, LCMV strains OQ28 and BRC were genetically classified in the same cluster of LCMV strains but exhibited very different pathogenicity. PMID- 22776052 TI - Modeling perimenopause in Sprague-Dawley rats by chemical manipulation of the transition to ovarian failure. AB - Various age-related diseases increase in incidence during perimenopause. However, our understanding of the effects of aging compared with hormonal changes of perimenopause in mediating these disease risks is incomplete, in part due to the lack of an experimental perimenopause model. We therefore aimed to determine whether manipulation of the transition to ovarian failure in rats via the use of 4-vinylcyclohexene diepoxide (VCD) could be used to model and accelerate hormonal changes characteristic of perimenopause. We examined long-term (11 to 20 mo), dose-dependent effects of VCD on reproductive function in 1- and 3-mo-old female Sprague-Dawley rats. Twenty-five daily doses of VCD (80 or 160 mg/kg daily compared with vehicle alone) depleted ovarian follicles in a dose-dependent fashion in rats of both ages, accelerated the onset of acyclicity, and caused dose-dependent increases in follicle-stimulating hormone that exceeded those naturally occurring with age in control rats but left serum levels of 17beta estradiol unchanged, with continued ovarian production of androstenedione. High dose VCD caused considerable nonovarian toxicities in 3-mo-old Sprague-Dawley rats, making this an unsuitable model. In contrast, 1-mo-old rats had more robust dose-dependent increases in follicle-stimulating hormone without evidence of systemic toxicity in response to either VCD dose. Because perimenopause is characterized by an increase in follicle-stimulating hormone with continued secretion of ovarian steroids, VCD acceleration of an analogous hormonal milieu in 1-mo-old Sprague-Dawley rats may be useful for probing the hormonal effects of perimenopause on age-related disease risk. PMID- 22776053 TI - Use of 18F-fluorodeoxyglucose positron emission tomography-computed tomography in a miniature pig (Sus scrofa domestica) with pneumonia. AB - A 1-y-old male miniature pig housed in our laboratory facility was evaluated for weight loss and rough coat condition. CBC results revealed neutrophilia. Radiography of the thoracic area showed increased opacity throughout the thoracic cavity except for the right caudal lobe. 18F-labeled fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) revealed elevated standard uptake values in the area corresponding to the radiologic findings. Follow-up thoracic radiography taken 2 wk after FDG-PET-CT showed several interval changes, including markedly decreased opacity throughout the entire thoracic cavity. Necropsy revealed adhesions between the upper portion of the caudal lobe of the left lung and thoracic wall. ELISA for several closely related infectious species confirmed the presence of antibody to Actinobacillus pleuropneumoniae serovar V. PMID- 22776054 TI - Effects of extended-release injectable naltrexone on self-injurious behavior in rhesus macaques (Macaca mulatta). AB - Self-injurious behavior (SIB) is a spontaneous behavior that threatens the health and wellbeing of multiple species. In humans, the opioid antagonist naltrexone hydrochloride has been used successfully to modulate the endogenous opioid system and reduce the occurrence of SIB. This study is the first to assess the efficacy of extended-release naltrexone in the pharmacologic treatment of SIB in rhesus macaques (Macaca mulatta). In an acute pharmacokinetic study of 4 macaques, we determined the mean naltrexone plasma concentration was maintained above the therapeutic level (2 ng/mL) after administration of a single dose (20 mg/kg) of 28-d extended-release naltrexone throughout the release period. For a subsequent treatment study, we selected 8 singly housed macaques known to engage in SIB. The study comprised a 4-wk baseline phase; an 8-wk treatment phase, during which each macaque received 2 doses of extended-release naltrexone 28 d apart; and a 4 wk posttreatment phase. Plasma samples were collected and analyzed weekly for naltrexone concentrations throughout the treatment and posttreatment phases. In addition, total of 6 h of video was analyzed per animal per phase of the study. Compared with baseline phases, both the frequency and the percentage of time spent displaying SIB decreased during the treatment phase, and the percentage of time remained decreased during the posttreatment phase. In contrast, extended release naltrexone did not alter the expression of other abnormal, anxiety related, or agonistic behaviors nor were levels of inactivity affected. The present study supports the use of naltrexone in the treatment of SIB in rhesus macaques. PMID- 22776055 TI - Variation in CCL3L1 copy number in rhesus macaques (Macaca mulatta). AB - We used real-time quantitative PCR (qPCR) methodology to examine copy number variation (CNV) of the CCL3L1 gene among pure Indian-origin, pure Chinese-origin, and hybrid Indian-Chinese rhesus macaques (Macaca mulatta). CNV among purebred macaques fell within expected ranges, with Indian macaques having lower copy numbers than those of Chinese macaques. Compared with the purebred macaques, Indian-Chinese hybrid rhesus macaques showed much greater variance in copy number and an intermediate average copy number. Copy numbers of CCL3L1 in rhesus macaque trios (sire, dam, and offspring) were consistent with Mendelian inheritance. PMID- 22776056 TI - Septic tularemia in 2 cottontop tamarins(Sanguinus oedipus). AB - Two captive cottontop tamarins (Sanguinus oedipus) died within 5 d of each other from systemic infection by Francisella tularensis (tularemia). One tamarin experienced mild clinical signs, including malaise, anorexia, and a mucoid nasal discharge for 4 d before death, whereas the other experienced a more rapid progression of disease that lasted less than 24 h. Differential diagnoses included gram-negative septicemia by an organism such as Escherichia coli, Salmonella, or Yersinia; protozoal infection such as Toxoplasma gondii or an acute viral infection such as lymphocytic choriomeningitis. F. tularensis infection was identified by F. tularensis-specific PCR in both primates. Possible sources of infection include aerosol, biting arthropod vectors, and transmission via a rodent reservoir. This case report highlights the importance of tularemia as a differential diagnosis in acute febrile illness in captive nonhuman primates. PMID- 22776057 TI - Acquired amegakaryocytic thrombocytopenia purpura in a Rhesus macaque (Macaca mulatta). AB - A 10-y-old multiparous rhesus macaque presented for an annual routine physical examination. Clinically, the animal had pale mucous membranes, petechial and ecchymotic hemorrhages in multiple sites, and a laceration at the tail base. Severe pancytopenia was noted on hematologic evaluation. The monkey was seronegative for SIV, simian T-lymphotropic virus, simian retrovirus type D, and Macacine herpesvirus 1. Bone marrow evaluation revealed a paucity of megakaryocytic precursors in a hypercellular marrow with marked erythroid hyperplasia. In light of these findings, the diagnosis was acquired amegakaryocytic thrombocytopenia purpura. Due to the poor prognosis of the syndrome and clinical deterioration of the monkey, euthanasia was elected. A definitive cause of the thrombocytopenia was not identified; however, the syndrome may have developed secondary to a recent spontaneous abortion. To our knowledge, this case represents the first reported observation of acquired amegakaryocytic thrombocytopenia purpura in a rhesus monkey. PMID- 22776058 TI - Successful reversal of complex regional pain syndrome type 1 of both upper extremities in five patients. PMID- 22776059 TI - Biracial couples and adverse birth outcomes: a systematic review and meta analyses. AB - BACKGROUND: Differences in birth outcomes such as low birthweight (LBW), preterm births (PTB), stillbirth, differences in birthweight in Black vs. White race are well known. Infants born to biracial parents (mother and father from either Black or White races) also experience higher adverse birth outcomes. OBJECTIVE: To systematically review and meta-analyze birth outcomes among parents of mixed racial background compared to parents of same race. SEARCH STRATEGY: Medline, Embase, CINAHL and bibliographies of identified articles were searched for English language studies. SELECTION CRITERIA: Studies reporting association between parental mixed racial status and LBW, PTB, or small-for-gestational age (SGA) outcomes were included. DATA COLLECTION AND ANALYSES: After exclusion of duplicate cohorts in different publications, data from White mother-Black father (WMBF), Black mother-White father (BMWF) and Black mother-Black father (BMBF) groups were compared with the White mother-White father (WMWF) group. RESULTS: Eight English language studies from of 26 335 596 singleton births were included and reviewed. Compared to the WMWF group, the adjusted odds ratio (95% confidence intervals) were: (a) low birthweight; 1.21 (1.10-1.33) for WMBF, 1.75(1.64-1.87) for BMWF, and 2.08 (1.81-2.38) for BMBF; (b) preterm births; 1.17 (1.05-1.31) for WMBF, 1.37 (1.18-1.59) for BMWF, and 1.78 (1.59-2.00) for BMBF; and (c) stillbirths; 1.43 (0.92-2.21) for WMBF, 1.51 (1.09-2.08) for BMWF, and 1.85 (1.47 2.32) for BMBF. CONCLUSION: Biracial status of parents was associated with higher risk for adverse pregnancy outcomes than both White parents but lower than both Black parents, with maternal race having a greater influence than paternal race on pregnancy outcomes. PMID- 22776060 TI - Sharing the trousers: gender roles and relationships in an HIV-prevention trial in Zimbabwe. AB - Male and female gender roles and inequalities are important in contributing to the disproportionate burden of HIV experienced by women in sub-Saharan Africa. Within the context of an HIV prevention trial, we aimed to describe and understand male partner influence on women's use of HIV-prevention methods. Our presumption was not that regressive gender norms prevailed - rather, that a wide range of gendered attitudes and dynamics would be expressed among couples. Data from 16 focus groups with Zimbabwean female trial participants and their male partners and 4 in-depth couples interviews were collected, and form the basis of the analysis. Findings offer descriptions of how couples have adapted techniques for negotiating modern household economies and sexual decision-making in a manner that both preserves traditional gender roles, while accommodating women's entrance into new domains such as the workforce or an HIV-prevention trial. Women's agency to introduce novel female-initiated-method use into her intimate relationships is described. Men and women's accounts of method introduction and use suggest different perceptions about the locus of sexual decision making. The study provides unique insight into a gendered context that is dynamic yet sensitive to change, which in turn can provide useful information to more appropriately guide HIV-prevention activities in this setting. PMID- 22776061 TI - Time-dependent effects of hypothermia on microglial activation and migration. AB - BACKGROUND: Therapeutic hypothermia is one of the neuroprotective strategies that improve neurological outcomes after brain damage in ischemic stroke and traumatic brain injury. Microglial cells become activated following brain injury and play an important role in neuroinflammation and subsequent brain damage. The aim of this study was to determine the time-dependent effects of hypothermia on microglial cell activation and migration, which are accompanied by neuroinflammation. METHODS: Microglial cells in culture were subjected to mild (33 degrees C) or moderate (29 degrees C) hypothermic conditions before, during, or after lipopolysaccharide (LPS) or hypoxic stimulation, and the production of nitric oxide (NO), proinflammatory cytokines, reactive oxygen species, and neurotoxicity was evaluated. Effects of hypothermia on microglial migration were also determined in in vitro as well as in vivo settings. RESULTS: Early-, co-, and delayed-hypothermic treatments inhibited microglial production of inflammatory mediators to varying degrees: early treatment was the most efficient, and delayed treatment showed time-dependent effects. Delayed hypothermia also suppressed the mRNA levels of proinflammatory cytokines and iNOS, and attenuated microglial neurotoxicity in microglia-neuron co-cultures. Furthermore, delayed hypothermia reduced microglial migration in the Boyden chamber assay and wound healing assay. In a stab injury model, delayed local hypothermia reduced migration of microglia toward the injury site in the rat brain. CONCLUSION: Taken together, our results indicate that delayed hypothermia is sufficient to attenuate microglial activation and migration, and provide the basis of determining the optimal time window for therapeutic hypothermia. Delayed hypothermia may be neuroprotective by inhibiting microglia-mediated neuroinflammation, indicating the therapeutic potential of post-injury hypothermia for patients with brain damages exhibiting some of the inflammatory components. PMID- 22776063 TI - Patient safety in psychiatric inpatient care: a literature review. AB - Patient safety is widely discussed, but little has been written from the perspective of psychiatric inpatient care, nor on which factors create its patient safety. This paper seeks to understand the concept of patient safety and its intension in psychiatric inpatient care, and to identify factors in organization management, staff and patients' roles which constitute patient safety in such units. A literature search was conducted, and the articles selected were analysed by identifying factors defined to be connected to patient safety and classifying them according to their connection to organization management, staff and patient roles. According to the literature, organization safety culture is present in all aspects of patient safety. Organization management has the main role in patient safety within the organization culture, for example, through leadership, safety practices and creating good working conditions and environment for the staff. Staff's role is influenced by management, but has more individual input in different areas, while the patient's role is more that of an informant so that care can be planned according to the patient's preferences. When developing patient safety it is important to remember the diversity of the concept so that all areas are considered in the developmental work. PMID- 22776062 TI - Environmental exposure to arsenic may reduce human semen quality: associations derived from a Chinese cross-sectional study. AB - BACKGROUND: Recent observations in in vitro and in vivo models suggest that arsenic (As) is an endocrine disruptor at environmentally-relevant levels. When exposed to As, male rats and mice show steroidogenic dysfunction that can lead to infertility. However, the possible effects of As on human male semen quality remain obscure. METHODS: We monitored the profile of As species in the urine of a reproductive-age human cohort and assessed its association with semen quality. Men (n = 96) were recruited in an infertility clinic from July 2009 to August 2010 in the Affiliated Hospital of Chongqing Institute for Population and Family Planning. Five urinary As species were analyzed by high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC ICP-MS). Clinical information on the semen volume, sperm concentration and motility was employed to catalogue and evaluate semen quality according to WHO guidelines. As species concentrations in addition to other continuous variables were dichotomized by the medians and modelled as categorical variables in order to explore using the binary logistic regression possible associations between As exposure and semen quality. RESULTS: Urinary concentrations (geometric mean +/- SD, MUg g(-1) creatinine) of different As species were 7.49 (+/- 24.8) for AsB, 20.9 (+/- 13.7) for DMA, 2.77 (+/- 3.33) for MMA, and 4.03 (+/- 3.67) for Asi (Asi(III )and Asi(V)). DMA concentrations above the median were significantly associated with below-reference sperm concentrations (P = 0.02) after adjusting for age, body mass index (BMI), abstinence, smoking and drinking habits. In addition, smoking was positively associated with MMA. CONCLUSION: Reduced parameters in human semen quality are positively associated with As exposure in a reproductive-age Chinese cohort. PMID- 22776064 TI - Early islet damage after direct exposure of pig islets to blood: has humoral immunity been underestimated? AB - Currently, islet transplantation as a cell therapeutic option for type 1 diabetes occurs via islet injection into the portal vein. Direct contact between islets and blood is a pathophysiological "provocation" that results in the instant blood mediated inflammatory reaction (IBMIR) and is associated with early islet loss. However, the nature of the various insults on the islets in the blood stream remains mostly unknown. To gain insight into the mechanisms, we utilized a simplified in vitro model in which islets were exposed to blood in different clinically relevant but increasingly challenging, autologous, allogeneic, and xenogeneic combinations. Irrespective of the blood type and species compatibility, islets triggered blood clotting. Islet damage was worse as islet, and blood compatibility diminished, with substantial islet injury after exposure of porcine islets to human blood. Islet damage involved membrane leakage, antibody deposition, complement activation, positive staining for the membrane attack complex, and mitochondrial dysfunction. Islet damage occurred even after exposure to plasma only, and specific complement inactivation and neutralization of IgM substantially prevented islet damage, indicating the importance of humoral immunity. Efficacious measures are needed to reduce this injury, especially in view of a potential clinical use of porcine islets to treat diabetes. PMID- 22776065 TI - Synthesis and evaluation of 2-chloro N-[(S)-{(S)-1-[11 C]methylpiperidin-2-yl} (phenyl)methyl]3-trifluoromethyl-benzamide ([11 C]N-methyl-SSR504734) as a PET radioligand for glycine transporter 1. AB - BACKGROUND: Dysfunction of the glycine transporter 1 (GlyT1) has been suggested to be involved in psychiatric disorders such as schizophrenia. GlyT1 inhibitors have therefore been considered to have antipsychotic therapeutic potential. Positron emission tomography (PET) imaging probes for GlyT1 are, consequently, expected to be useful for investigating the mechanism of such disease conditions and for measuring occupancy of GlyT1 inhibitors in vivo. The aim of this study was to assess the potential of 2-chloro N-[(S)-{(S)-1-[11 C]methylpiperidin-2-yl} (phenyl)methyl] 3-trifluoromethyl-benzamide ([11 C]N-methyl-SSR504734) as a PET imaging agent for GlyT1. METHODS: [11 C]N-methyl-SSR504734 was synthesized by N [11 C]methylation of SSR504734 via [11 C]CH3OTf. In vitro brain distribution of [11 C]N-methyl-SSR504734 was tested in whole-hemisphere autoradiography (ARG) on human brain slices. Initial PET studies were performed using a cynomolgus monkey at baseline and after pretreatment with 0.1 to 1.5 mg/kg of SSR504734. Then, PET studies using rhesus monkeys were performed with arterial blood sampling at baseline and after pretreatment with 1.5 to 4.5 mg/kg SSR504734. Distribution volumes (VT) were calculated with a two-tissue compartment model, and GlyT1 occupancy by SSR504734 was estimated using a Lassen plot approach. RESULTS: [11 C]N-methyl-SSR504734 was successfully synthesized in moderate radiochemical yield and high specific radioactivity. In the ARG experiments, [11 C]N-methyl-SSR504734 showed specific binding in the white matter and pons. In the initial PET experiments in a cynomolgus monkey, [11 C]N-methyl-SSR504734 showed high brain uptake and consistent distribution with previously reported GlyT1 expression in vivo (thalamus, brainstem > cerebellum > cortical regions). However, the brain uptake increased after pretreatment with SSR504734. Further PET studies in rhesus monkeys showed a similar increase of brain uptake after pretreatment with SSR504734. However, the VT of [11 C]N-methyl-SSR504734 was found to decrease after pretreatment of SSR504734 in a dose-dependent manner. GlyT1 occupancy was calculated to be 45% and 73% at 1.5 and 4.5 mg/kg of SSR504734, respectively. CONCLUSIONS: [11 C]N-methyl-SSR504734 is demonstrated to be a promising PET radioligand for GlyT1 in nonhuman primates. The present results warrant further PET studies in human subjects. PMID- 22776066 TI - A cluster randomised controlled trial of an occupational therapy intervention for residents with stroke living in UK care homes (OTCH): study protocol. AB - BACKGROUND: The occupational therapy (OT) in care homes study (OTCH) aims to investigate the effect of a targeted course of individual OT (with task training, provision of adaptive equipment, minor environmental adaptations and staff education) for stroke survivors living in care homes, compared to usual care. METHODS/DESIGN: A cluster randomised controlled trial of United Kingdom (UK) care homes (n = 90) with residents (n = 900) who have suffered a stroke or transient ischaemic attack (TIA), and who are not receiving end-of-life care. Homes will be stratified by centre and by type of care provided and randomised (50:50) using computer generated blocked randomisation within strata to receive either the OT intervention (3 months intervention from an occupational therapist) or control (usual care). Staff training on facilitating independence and mobility and the use of adaptive equipment, will be delivered to every home, with control homes receiving this after the 12 month follow-up.Allocation will be concealed from the independent assessors, but the treating therapists, and residents will not be masked to the intervention. Measurements are taken at baseline prior to randomisation and at 3, 6 and 12 months post randomisation. The primary outcome measure is independence in self-care activities of daily living (Barthel Activities of Daily Living Index). Secondary outcome measures are mobility (Rivermead Mobility Index), mood (Geriatric Depression Scale), preference based quality of life measured from EQ-5D and costs associated with each intervention group. Quality adjusted life years (QALYs) will be derived based on the EQ-5D scores. Cost effectiveness analysis will be estimated and measured by incremental cost effectiveness ratio. Adverse events will be recorded. DISCUSSION: This study will be the largest cluster randomised controlled trial of OT in care homes to date and will clarify the currently inconclusive literature on the efficacy of OT for stroke and TIA survivors residing in care homes. TRIAL REGISTRATION: ISRCTN00757750. PMID- 22776067 TI - ParticleCall: a particle filter for base calling in next-generation sequencing systems. AB - BACKGROUND: Next-generation sequencing systems are capable of rapid and cost effective DNA sequencing, thus enabling routine sequencing tasks and taking us one step closer to personalized medicine. Accuracy and lengths of their reads, however, are yet to surpass those provided by the conventional Sanger sequencing method. This motivates the search for computationally efficient algorithms capable of reliable and accurate detection of the order of nucleotides in short DNA fragments from the acquired data. RESULTS: In this paper, we consider Illumina's sequencing-by-synthesis platform which relies on reversible terminator chemistry and describe the acquired signal by reformulating its mathematical model as a Hidden Markov Model. Relying on this model and sequential Monte Carlo methods, we develop a parameter estimation and base calling scheme called ParticleCall. ParticleCall is tested on a data set obtained by sequencing phiX174 bacteriophage using Illumina's Genome Analyzer II. The results show that the developed base calling scheme is significantly more computationally efficient than the best performing unsupervised method currently available, while achieving the same accuracy. CONCLUSIONS: The proposed ParticleCall provides more accurate calls than the Illumina's base calling algorithm, Bustard. At the same time, ParticleCall is significantly more computationally efficient than other recent schemes with similar performance, rendering it more feasible for high-throughput sequencing data analysis. Improvement of base calling accuracy will have immediate beneficial effects on the performance of downstream applications such as SNP and genotype calling. PMID- 22776068 TI - Predicting the risk of psychosis onset: advances and prospects. AB - AIM: To conduct a systematic review of the methods and performance characteristics of models developed for predicting the onset of psychosis. METHODS: We performed a comprehensive literature search restricted to English articles and identified using PubMed, Medline and PsychINFO, as well as the reference lists of published studies and reviews. Inclusion criteria included the selection of more than one variable to predict psychosis or schizophrenia onset, and selection of individuals at familial risk or clinical high risk. Eighteen studies met these criteria, and we compared these studies based on the subjects selected, predictor variables used and the choice of statistical or machine learning methods. RESULTS: Quality of life and life functioning as well as structural brain imaging emerged as the most promising predictors of psychosis onset, particularly when they were coupled with appropriate dimensionality reduction methods and predictive model algorithms like the support vector machine (SVM). Balanced accuracy ranged from 100% to 78% in four studies using the SVM, and 67% to 81% in 14 studies using general linear models. CONCLUSIONS: Performance of the predictive models improves with quality of life measures, life functioning measures, structural brain imaging data, as well as with the use of methods like SVM. Despite these advances, the overall performance of psychosis predictive models is still modest. In the future, performance can potentially be improved by including genetic variant and new functional imaging data in addition to the predictors that are used currently. PMID- 22776070 TI - Risk of invasive breast cancer and ductal carcinoma in situ in women with atypical papillary lesions of the breast. AB - Benign papillary lesions of the breast include papilloma and papillomatosis. A retrospective analysis of patients with a papillary breast lesion diagnosed between October 1992 and December 2009 was performed. Patients were excluded if they had a previous or concurrent diagnosis of invasive or in situ cancer or less than 6 months of follow-up. The Kaplan-Meier method was used to determine the risk of developing subsequent malignancy. The log rank test was used to compare groups of patients. Median follow-up for the 167 patients included in the study was 4.6 years. Fifty-one patients had a papillary lesion with atypia and 116 patients had a papillary lesion without atypia. Patients with a papillary lesion with atypia were more likely to develop invasive or in situ breast cancer with a 5 year risk of 13.0% versus 4.6% in patients with no atypia (p = 0.03). PMID- 22776069 TI - Inhibition of CD200R1 expression by C/EBP beta in reactive microglial cells. AB - BACKGROUND: In physiological conditions, it is postulated that neurons control microglial reactivity through a series of inhibitory mechanisms, involving either cell contact-dependent, soluble-factor-dependent or neurotransmitter-associated pathways. In the current study, we focus on CD200R1, a microglial receptor involved in one of these cell contact-dependent mechanisms. CD200R1 activation by its ligand, CD200 (mainly expressed by neurons in the central nervous system),is postulated to inhibit the pro-inflammatory phenotype of microglial cells, while alterations in CD200-CD200R1 signalling potentiate this phenotype. Little is known about the regulation of CD200R1 expression in microglia or possible alterations in the presence of pro-inflammatory stimuli. METHODS: Murine primary microglial cultures, mixed glial cultures from wild-type and CCAAT/enhancer binding protein beta (C/EBPbeta)-deficient mice, and the BV2 murine cell line overexpressing C/EBPbeta were used to study the involvement of C/EBPbeta transcription factor in the regulation of CD200R1 expression in response to a proinflammatory stimulus (lipopolysaccharide (LPS)). Binding of C/EBPbeta to the CD200R1 promoter was determined by quantitative chromatin immunoprecipitation (qChIP). The involvement of histone deacetylase 1 in the control of CD200R1 expression by C/EBPbeta was also determined by co-immunoprecipitation and qChIP. RESULTS: LPS treatment induced a decrease in CD200R1 mRNA and protein expression in microglial cells, an effect that was not observed in the absence of C/EBPbeta. C/EBPbeta overexpression in BV2 cells resulted in a decrease in basal CD200R1 mRNA and protein expression. In addition, C/EBPbeta binding to the CD200R1 promoter was observed in LPS-treated but not in control glial cells, and also in control BV2 cells overexpressing C/EBPbeta. Finally, we observed that histone deacetylase 1 co-immunoprecipitated with C/EBPbeta and showed binding to a C/EBPbeta consensus sequence of the CD200R1 promoter in LPS-treated glial cells. Moreover, histone deacetylase 1 inhibitors reversed the decrease in CD200R1 expression induced by LPS treatment. CONCLUSIONS: CD200R1 expression decreases in microglial cells in the presence of a pro-inflammatory stimulus, an effect that is regulated, at least in part, by C/EBPbeta. Histone deacetylase 1 may mediate C/EBPbeta inhibition of CD200R1 expression, through a direct effect on C/EBPbeta transcriptional activity and/or on chromatin structure. PMID- 22776071 TI - Non-immersive, virtual reality mirror visual feedback for treatment of persistent idiopathic facial pain. PMID- 22776073 TI - Computed tomography and cross-sectional anatomy of the metatarsus and digits of the one-humped camel (Camelus dromedarius) and buffalo ( Bos bubalis). AB - The purpose of the present study was to provide a detailed computed tomography (CT) and cross-sectional anatomic reference of the normal metatarsus and digits for the camel and buffalo, as well as to compare between metatarsus and digits in these animals to outstand a basis for diagnosis of their diseases. Advantages, including depiction of detailed cross-sectional anatomy, improved contrast resolution and computer reformatting, make it a potentially valuable diagnostic technique. The hind limbs of 12 healthy adult camel and buffalo were used. Clinically relevant anatomic structures were identified and labelled at each level in the corresponding images (CT and anatomic slices). CT images were used to identify the bony and soft tissue structures of the metatarsus and digits. The knowledge of normal anatomy of the camel and buffalo metatarsus and digits would serve as initial reference to the evaluation of CT images in these species. PMID- 22776072 TI - Assessment of the structural and functional impact of in-frame mutations of the DMD gene, using the tools included in the eDystrophin online database. AB - BACKGROUND: Dystrophin is a large essential protein of skeletal and heart muscle. It is a filamentous scaffolding protein with numerous binding domains. Mutations in the DMD gene, which encodes dystrophin, mostly result in the deletion of one or several exons and cause Duchenne (DMD) and Becker (BMD) muscular dystrophies. The most common DMD mutations are frameshift mutations resulting in an absence of dystrophin from tissues. In-frame DMD mutations are less frequent and result in a protein with partial wild-type dystrophin function. The aim of this study was to highlight structural and functional modifications of dystrophin caused by in frame mutations. METHODS AND RESULTS: We developed a dedicated database for dystrophin, the eDystrophin database. It contains 209 different non frame shifting mutations found in 945 patients from a French cohort and previous studies. Bioinformatics tools provide models of the three-dimensional structure of the protein at deletion sites, making it possible to determine whether the mutated protein retains the typical filamentous structure of dystrophin. An analysis of the structure of mutated dystrophin molecules showed that hybrid repeats were reconstituted at the deletion site in some cases. These hybrid repeats harbored the typical triple coiled-coil structure of native repeats, which may be correlated with better function in muscle cells. CONCLUSION: This new database focuses on the dystrophin protein and its modification due to in frame deletions in BMD patients. The observation of hybrid repeat reconstitution in some cases provides insight into phenotype-genotype correlations in dystrophin diseases and possible strategies for gene therapy. The eDystrophin database is freely available: http://edystrophin.genouest.org/. PMID- 22776074 TI - rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes. AB - OBJECTIVE: To evaluate UBASH3A (rs11203203) as a predictor of persistent islet autoimmunity (IA) and type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The Diabetes Autoimmunity Study in the Young (DAISY) followed prospectively for development of persistent IA (autoantibodies to insulin, GAD65, IA-2, or ZnT8 on at least two consecutive exams) and diabetes 1715 non-Hispanic white children at increased genetic risk for T1D. The DAISY participants were genotyped for rs11202203 (UBASH3A). RESULTS: UBASH3A allele A was associated with development of IA [hazard ratio (HR) = 1.46, 95%CI = 1.11-1.91, p = 0.007] and diabetes (HR = 1.84, 95%CI = 1.28-2.64, p = 0.001), controlling for presence of HLA DR3/4,DQB1*0302 and having a first-degree relative (FDR) with T1D. The UBASH3A AA genotype conferred higher risk of persistent IA (12.7%) and diabetes (6.1%) by age 10 than for AG (7.7 and 3.1%, respectively) or GG (5.3 and 2.0%) genotype (p = 0.009 for IA, p = 0.0004 for diabetes). Among children with no family history of T1D, but HLA-DR3/4,DQB1*0302 and UBASH3A AA genotype, 35.9% developed IA and 50.6% developed diabetes by age 15. CONCLUSIONS: UBASH3A appears to be an independent predictor of IA and T1D in children, including those free of family history of T1D but carrying the HLA-DR3/4,DQB1*0302 genotype. If confirmed, UBASH3A may prove useful in T1D risk prediction and pre-screening of the general population children for clinical trials. PMID- 22776075 TI - Land-use and land-cover assessment for the study of lifestyle change in a rural Mexican community: the Maycoba project. AB - BACKGROUND: In 1995, a study was conducted to identify the effects of traditional and westernized environments on the prevalence of type 2 diabetes in Pima Indians (Pimas) in Mexico and the United States. The study concluded that the more traditional lifestyle in Mexico had a protective effect against this metabolic disorder. In the ensuing 15 years, the environmental circumstances of the Mexican Pimas changed, and a follow-up study was conducted to determine the role environmental change plays in the development of diabetes in this genetically susceptible population. A major element of environmental transition relates to land-use and land-cover (LULC) changes that could affect physical activity and promote an obesogenic environment. This study examined changes in the region's LULC to determine whether there have been transitions in agricultural land use and urbanization that would be consistent with a more sedentary lifestyle. Changes were assessed from 1994 aerial photographs and 2007 satellite images. RESULTS: The land-cover analysis showed that mixed vegetation and dense trees cover most of the study area. It suggested a rural environment that includes a low percentage of impermeable areas, and it indicated that the area experiencing human intervention covers 7% of the total area. The land-use-change findings showed a decrease or no change in agricultural or ranching areas and a decrease in farmland due to reforestation or revegetation. Three variables from the land use-change analysis were examined as proxies for lifestyle change: urban development, dwelling-unit density, and variation in the road network. Two of the measures -the amount of urbanization and the number and density of dwelling units showed increases, most notably in the town of Maycoba. There were only minor changes in the road network: most of the road segments are short and concentrated in Maycoba where most of the buildings, points of interest (e.g., church, stores), and cars are located. CONCLUSIONS: The LULC in Maycoba and surrounding settlements had changed during the study period. LULC change was used as a proxy to examine lifestyle changes that can affect levels of physical activity. PMID- 22776076 TI - Multidisciplinary management of patients with haemophilia with inhibitors undergoing surgery in the United States: perspectives and best practices derived from experienced treatment centres. AB - Since the 1980s, major surgical interventions in patients with congenital haemophilia with inhibitors have been performed utilizing bypassing agents for haemostatic coverage. While reports have focused on perioperative management and haemostasis, the US currently lacks consensus guidelines for the management of patients with inhibitors during the surgical procedure, and pre- and postoperatively. Many haemophilia treatment centres (HTCs) have experience with surgery in haemophilia patients, including those with inhibitors, with approximately 50% of these HTCs having performed orthopaedic procedures. The aim of this study was to present currently considered best practices for multidisciplinary care of inhibitor patients undergoing surgery in US HTCs. Comprehensive haemophilia care in the US is provided by ~130 federally designated HTCs staffed by multidisciplinary teams of healthcare professionals. Best practices were derived from a meeting of experts from leading HTCs examining the full care spectrum for inhibitor patients ranging from identification of the need for surgery through postoperative rehabilitation. HTCs face challenges in the care of inhibitor patients requiring surgery due to the limited number of surgeons willing to operate on this complex population. US centres of excellence have developed their own best practices around an extended comprehensive care model that includes preoperative planning, perioperative haemostasis and postoperative rehabilitation. Best practices will benefit patients with inhibitors and allow improvement in the overall care of these patients when undergoing surgical procedures. In addition, opportunities for further education and outcomes assessment in the care of this patient population have been identified. PMID- 22776077 TI - Male sexual function after laparoscopic total mesorectal excision. AB - AIM: The aim of this prospective study was to clarify the frequency of male sexual dysfunction after laparoscopic total mesorectal excision (LTME) and to examine the relationship between pelvic autonomic nerve (PAN) preservation status and functional outcomes. METHOD: Candidates for LTME were included in this study. PAN preservation status after LTME was examined in detail by video review. Patients completed a functional questionnaire (the International Index of Erectile Function) before and 3, 6 and 12 months after the operation. RESULTS: Twenty-six patients who underwent LTME were assessable. Detailed video reviews identified inadvertent PAN damage during surgery. PAN injury was observed in 11 cases (41%), including eight cases (32%) of inadvertent PAN damage (incomplete preservation group). There was a trend toward increasing inadvertent PAN injury rate in patients with high body mass index and large tumours. The results from all patients who underwent LTME showed no deterioration in total International Index of Erectile Function or its domain scores 12 months after surgery. In the incomplete preservation group, these scores temporarily decreased (3 and 6 months after surgery), but such deterioration was not observed in the complete preservation group. Most of the 12 patients with potentially active erectile function before the operation recovered this function, and only one patient (7%) with PAN injury was still judged as inactive 12 months after surgery. CONCLUSION: The proportion of patients with sexual dysfunction after LTME is low. With the enhanced visibility of the laparoscope, inadvertent PAN injury was detected in a significant number of cases and associated with transient deterioration of sexual function. PMID- 22776078 TI - Corticospinal tract integrity and motor function following neonatal stroke: a case study. AB - BACKGROUND: New MRI techniques enable visualisation of corticospinal tracts and cortical motor activity. The objective of this case study was to describe the magnetic resonance evidence of corticospinal pathway reorganisation following neonatal stroke. CASE PRESENTATION: An 11 year old boy with a neonatal right middle cerebral artery territory ischaemic stroke was studied. Functional MRI was undertaken with a whole hand squeezing task, comparing areas of cortical activation between hands. White matter tracts, seeded from the area of peak activation in the cortex, were visualised using a diffusion weighted imaging probabilistic tractography method. Standardised evaluations of unilateral and bilateral motor function were undertaken. Clinically, the child presented with a left hemiparesis. Functional MRI demonstrated that movement of the hemiparetic hand resulted in activation in the ipsi-lesional (right) hemisphere only. Diffusion tractography revealed pathways in the right (lesioned) hemisphere tracked perilesionally to the cortical area identified by functional MRI. CONCLUSION: Our case demonstrates that neonatal stroke is associated with maintenance of organization of corticospinal pathways sufficient to maintain some degree of hand function in the affected hemisphere. Functional MRI and diffusion weighted imaging tractography may inform our understanding of recovery, organisation and reorganisation and have the potential to monitor responses to intervention following neonatal stroke. PMID- 22776079 TI - Concept annotation in the CRAFT corpus. AB - BACKGROUND: Manually annotated corpora are critical for the training and evaluation of automated methods to identify concepts in biomedical text. RESULTS: This paper presents the concept annotations of the Colorado Richly Annotated Full Text (CRAFT) Corpus, a collection of 97 full-length, open-access biomedical journal articles that have been annotated both semantically and syntactically to serve as a research resource for the biomedical natural-language-processing (NLP) community. CRAFT identifies all mentions of nearly all concepts from nine prominent biomedical ontologies and terminologies: the Cell Type Ontology, the Chemical Entities of Biological Interest ontology, the NCBI Taxonomy, the Protein Ontology, the Sequence Ontology, the entries of the Entrez Gene database, and the three subontologies of the Gene Ontology. The first public release includes the annotations for 67 of the 97 articles, reserving two sets of 15 articles for future text-mining competitions (after which these too will be released). Concept annotations were created based on a single set of guidelines, which has enabled us to achieve consistently high interannotator agreement. CONCLUSIONS: As the initial 67-article release contains more than 560,000 tokens (and the full set more than 790,000 tokens), our corpus is among the largest gold-standard annotated biomedical corpora. Unlike most others, the journal articles that comprise the corpus are drawn from diverse biomedical disciplines and are marked up in their entirety. Additionally, with a concept-annotation count of nearly 100,000 in the 67-article subset (and more than 140,000 in the full collection), the scale of conceptual markup is also among the largest of comparable corpora. The concept annotations of the CRAFT Corpus have the potential to significantly advance biomedical text mining by providing a high-quality gold standard for NLP systems. The corpus, annotation guidelines, and other associated resources are freely available at http://bionlp-corpora.sourceforge.net/CRAFT/index.shtml. PMID- 22776080 TI - Pain mechanisms in multiple sclerosis. PMID- 22776081 TI - Red blood cell transfusion is associated with troponin release after elective off pump coronary artery bypass surgery. AB - BACKGROUND: Increased troponin levels after coronary artery bypass surgery are associated with increased risk of early and late mortality. We hypothesized that perioperative blood transfusion is associated with increased postoperative troponin release. METHODS: Complete data on perioperative blood transfusion and troponin I were available for 140 patients who underwent isolated, elective off pump coronary artery bypass graft surgery. RESULTS: Linear regression analysis showed that red blood cell (RBC) transfusion (p=0.007) was an independent predictor of troponin I levels on the first postoperative day. The RBC transfusion was associated with a high risk of type V myocardial infarction as indicated by troponin I levels greater than 6.6 MUg/L on the first postoperative day (9 of 58 patients [15.5%] versus 1 of 82 patients [1.2%], p=0.002; adjusted analysis odds ratio 14.878, 95% confidence interval: 1.829 to 121.033). This finding did not change when hemoglobin and hematocrit nadirs were included in the analysis. Repeated-measure test showed that any blood product transfusion (p=0.040), any blood product transfusion on the operation day (p=0.025), any RBC transfusion (p=0.014), and RBC transfusion on the operation day (p=0.026) were associated with increased postoperative troponin I release. These findings persisted even after adjusting for hemoglobin and hematocrit nadirs. CONCLUSIONS: Red blood cell transfusion is associated with increased troponin I release after elective off-pump coronary artery bypass graft surgery independently of hemoglobin and hematocrit nadirs. These findings suggest that prevention of major bleeding requiring blood transfusion may be cardioprotective during coronary surgery. Further studies are needed to verify whether troponin release is affected simply by RBC transfusion or by unstable hemodynamic conditions in presence of mild and severe anemia. PMID- 22776082 TI - Sternotomy versus nonsternotomy LIMA-LAD grafting for single-vessel disease. AB - BACKGROUND: Single-vessel disease of the left anterior descending (LAD) coronary artery may be surgically revascularized by left internal mammary artery (LIMA) grafting either through a sternotomy or a nonsternotomy approach. Nonsternotomy approaches are used in the hope of achieving a less invasive operation. It is unknown whether nonsternotomy approaches impact in-hospital or midterm outcomes. METHODS: The institutional Society of Thoracic Surgeons (STS) database at a single US academic center was reviewed for 597 consecutive patients treated surgically for single-vessel LAD disease from January 1, 2002 to June 30, 2011. In-hospital adverse events and length of stay (LOS) were compared between patients who had LIMA-LAD grafting performed through a sternotomy (sternotomy patients) versus patients who had this procedure performed through a nonsternotomy approach (nonsternotomy patients), adjusted for propensity score (likelihood of receiving sternotomy, calculated on 33 variables). Midterm survival between groups was compared using Kaplan-Meier and Cox regression analysis by referencing the National Social Security Death Index. RESULTS: There were 597 consecutive patients who underwent single-vessel grafting by LIMA-LAD coronary artery grafting. Of these patients, 234 underwent sternotomy, whereas 363 patients had nonsternotomy procedures: 239 patients had endoscopic LIMA harvest and left anterolateral thoracotomy, 106 patients had robot LIMA harvest and left anterolateral thoracotomy, and 18 patients had minimally invasive direct coronary artery bypass. There were no strokes in the nonsternotomy group and 3 (1.3%) in the sternotomy group (p = 0.031). Thirty-day mortality, incidence of myocardial infarction, hospital LOS, and midterm survival were similar between groups. Operative time was significantly longer in the nonsternotomy group (1.8 hours, 95% confidence interval [CI], 1.5-2.1). CONCLUSIONS: In this propensity adjusted comparison, sternal-sparing incisions were associated with similar 30 day adverse events and midterm survival compared with sternotomy for single vessel LIMA-LAD artery grafting. PMID- 22776083 TI - Complete thoracic mediastinal lymphadenectomy leads to a higher rate of pathologically proven N2 disease in patients with non-small cell lung cancer. AB - BACKGROUND: The American College of Surgery Oncology Group Z0030 study was a prospective randomized study that showed that mediastinal lymph node sampling (MLNS) offered similar results to mediastinal lymph node dissection (MLND) in patients with non-small cell lung cancer (NSCLC). However, that study only randomized patients after thorough samplings that were negative on frozen section in several N2 and N1 nodal stations. The purpose of this study was to evaluate the effect of MLND to the more common practice of ruling out N2 disease preoperatively and then resection without sending lymph nodes for frozen section. METHODS: This is a retrospective study of patients clinically staged as N0 with NSCLC. The incidence of pathologic N2 disease reported by the Society of Thoracic Surgeons (STS) database was considered to represent MLNS and it was compared with our patients who underwent complete MLND. RESULTS: Between January 2002 and December 2009, 1,358 patients clinically staged as N0 underwent lobectomy or segmentectomy and MLND (not MLNS). Our incidence of pathologic N2 disease in 1,107 patients who underwent lobectomy was 10.6% compared with 9.4% in the 24,896 STS lobectomy patients (p=0.196). Our incidence of pathologic N2 disease in 251 patients who underwent segmentectomy was 13.0% compared with 5.3% in the 2,150 STS segmentectomy patients (p<0.001). CONCLUSIONS: When complete MLND is performed in patients during pulmonary resection who are clinically node negative (have benign N2 nodes after selective endobronchial or esophageal ultrasound or mediastinoscopy) without using intraoperative frozen section of N2 or N1, more patients are pathologically staged with N2 disease; thus, more are considered for adjuvant chemotherapy. The impact on survival in these patients is unproven. PMID- 22776084 TI - Transcatheter-based aortic valve implantations at midterm: what happened to our initial patients? AB - BACKGROUND: This report analyzes a single institution's results with transapical aortic valve implantation (TAVI) from an initial series of patients over 5 years. METHODS: A series of 100 patients underwent TAVI at our institution between January 2005 and December 2008. The mean patient age was 85 +/- 6 years. All patients had a high perioperative risk for aortic valve replacement (mean logistic EuroSCORE of 36% +/- 12%; Society of Thoracic Surgeons [STS] score 16% +/- 3%). Clinical and echocardiographic variables were entered prospectively into a database. Late follow-up for survival, clinical outcomes including the New York Heart (NYHA) Association functional class, and echocardiographic assessment was 100% complete. RESULTS: After a mean follow-up of 3.8 +/- 2 years, overall mortality was 13% (n = 13/100), 30-day mortality was 8% (8/100), and late mortality was 5% (5/100). There were 2 perioperative repeated thoracotomies for bleeding, 2 intraoperative conversions, 1 prosthesis embolization, and 2 cases of impairment of coronary arteries. The causes of late mortality were cardiac failure (n = 2), respiratory failure (n = 1), renal failure (n = 1), and cancer (n = 1). At late follow-up there were no cases of endocarditis or stroke in any of the patients. None of the valves showed structural valve degeneration. NYHA functional class improved from 3.4 +/- 0.4 before operation to 1.9 +/- 0.5 at late follow-up (p = 0.02). Only 4 patients did not improve in functional class. CONCLUSIONS: Midterm outcomes after TAVI in high-risk patients at our institution show an improvement in functional capacity, with a good survival rate. Valve degeneration is not an issue at midterm follow-up. PMID- 22776085 TI - Aortic expansion after acute type B aortic dissection. AB - BACKGROUND: A considerable number of patients with acute type B aortic dissection (ABAD) treated with medical management alone will exhibit aortic enlargement during follow-up, which could lead to aortic aneurysm and rupture. The purpose of this study was to investigate predictors of aortic expansion among ABAD patients enrolled in the International Registry of Acute Aortic Dissection. METHODS: We analyzed 191 ABAD patients treated with medical therapy alone enrolled in the registry between 1996 and 2010, with available descending aortic diameter measurements at admission and during follow-up. The annual aortic expansion rate was calculated for all patients, and multivariate regression analysis was used to investigate factors affecting the expansion rate. RESULTS: Aortic expansion was observed in 59% of ABAD patients; mean expansion rate was 1.7+/-7 mm/y. In multivariate analysis, white race (regression coefficient [RC], 4.6; 95% confidence interval [CI], 1.4 to 7.7) and an initial aortic diameter less than 4.0 cm (RC, 6.3; 95% CI, 4.0 to 8.6) were associated with increased aortic expansion. Female sex (RC, -3.8; 95% CI, -6.1 to -1.4), intramural hematoma (RC, 3.8; 95% CI, -6.5 to -1.1), and use of calcium-channel blockers (RC, -3.8; 95% CI, -6.2 to -1.3) were associated with decreased aortic expansion. CONCLUSIONS: White race and a small initial aortic diameter were associated with increased aortic expansion during follow-up, and decreased aortic expansion was observed among women, patients with intramural hematoma, and those on calcium-channel blockers. These data raise the possibility that the use of calcium-channel blockers after ABAD may reduce the rate of aortic expansion, and therefore further investigation is warranted. PMID- 22776086 TI - Bronchovascular reconstruction for lung cancer: does induction chemotherapy influence the outcomes? AB - BACKGROUND: Bronchoangioplastic interventions (BAIs) for lung cancer are challenging procedures associated with a high risk of postoperative morbidity and mortality. The role of induction chemotherapy (IC) in these patients is debated. METHODS: We reviewed clinical records of patients who underwent a BAI between 1998 and 2009 using a prospective clinical and operative database. RESULTS: Among 47 patients (39 men; mean age, 66 years) who underwent BAI, 26 (55.3%) received IC for N2 disease or for locally advanced lung cancer. We performed 35 pulmonary artery (PA) sleeve resections (31 partial and 4 circumferential), 10 PA reconstructions with a pericardial patch (8 autologous, and 2 heterologous), and 2 PA reconstructions using heterologous conduit. The 30-day mortality rate was 4.2% (n=2). Morbidity occurred in 19 (40.4%) patients; 5 patients (10.6%) had major complications (3 [6.4%] patients with fatal bronchovascular fistulas and 1 patient each with cardiac dislocation and acute respiratory distress syndrome) (2.2%). Fourteen patients (29.8%) had minor complications: 6 (12.7%) cardiac, 7 (14.9%) pulmonary, and 1 (2.2%) stroke. IC did not influence the complication rate. Overall 5-year survival and disease-free survival was 39.2% and 36.9%, respectively. Early pathologic stage and the absence of nodal involvement significantly influenced survival (p=0.005 and p=0.002, respectively). Patients receiving IC had a better prognosis (62.7% versus 10.7%; p=0.0003). At multivariate analysis, IC influenced long-term survival (p=0.003 [95% CI, 2.92 8.56]). CONCLUSIONS: BAIs are feasible and effective surgical procedures with acceptable morbidity and mortality. IC does not influence morbidity and allows good long-term outcomes. PMID- 22776088 TI - Tissue-engineered bone grafts for osteoplasty in patients with cleft alveolus. AB - Alveolar bone grafting is an integral part of the treatment concept in cleft palate patients. As an alternative to autogenous bone, tissue-engineered grafts have found some clinical application. The aim of the present study has been to compare ossification in the cleft area using tissue-engineered grafts in a case series of patients with ossification after transplantation of autogenous spongious bone as the gold standard in alveoloplasty. Eight children with complete cleft lips and cleft palates were included in the study. In four children (group A), the cleft defect was filled with tissue-engineered bone (autogenous osteoblasts cultured on demineralized bone matrix Osteovit((r))); as control in another 4 children (group B), the alveoloplasty was performed using spongious iliac bone. Preoperative and 6 months postoperative cone-beam computed tomography was performed, and volumes of the remaining cleft defects were calculated using 3D navigation software. Wound healing was uneventful in both groups. Six months postoperatively the mean volume of the cleft was 0.55+/ 0.24cm(3) after grafting of tissue-engineered bone (group A) and 0.59+/-0.23cm(3) after transplantation of autogenous spongiosa. In group A, 40.9% of the cleft defect was ossified; in the control group (group B), 36.6%. Tissue-engineered bone is a promising alternative in alveolar bone grafting and no disadvantages were observed in comparison to the gold standard. PMID- 22776087 TI - Whole genome expression profile in neuroblastoma cells exposed to 1-methyl-4 phenylpyridine. AB - Mitochondrial dysfunction and subsequent energy failure is a contributing factor to degeneration of the substantia nigra pars compacta associated with Parkinson's disease (PD). In this study, we investigate molecular events triggered by cell exposure to the mitochondrial toxin 1-methyl-4-phenylpyridine (MPP+) using whole genome-expression microarray, Western Blot and metabolic studies. The data show that MPP+ (500 MUM) obstructs mitochondrial respiration/oxidative phosphorylation (OXPHOS) in mouse neuroblastoma Neuro-2a cells, juxtaposing accelerated glucose consumption and production of lactic acid. While additional glucose concentrations restored viability in the presence of MPP+ (500 MUM), the loss of OXPHOS was sustained, suggesting that compensatory anaerobic metabolic systems were fulfilling required energy needs. Under these conditions, MPP+ initiated significant changes to the transcription of 439 genes of which 287 DAVID IDs were identified and subsequent functional annotation clusters identified. Prominent changes were as follows; MPP+ initiated loss of mRNA for mitochondrial encoded 3 hydroxybutyratedehydrogenase, type 2(Bdh2), tv1, NADH dehydrogenase 4,5 genes, cytochrome b and NADH dehydrogenase (ubiquinone) flavoprotein 3, concomitant to rise in a mitochondrial fission gene; ganglioside-induced differentiation associated-protein 1 (GDAP1). The negative changes to OXPHOS components were accompanied by protective forces within the mitochondria espousing elevated ratio of anti/pro-apoptotic processes. These included a loss of apoptotic Bcl 2/adenovirus E1B 19-kDa-interacting protein (BNIP3) and family with sequence similarity 162, member A (FAM162a) and rise of heat shock protein 1 and Lon peptidase 1. There were no changes indicative of free radical damage (e.g. SOD, GSH-Px), rather MPP+ initiated significant elevation in G protein signaling components (which trigger catabolic processes) and anaerobic metabolic systems involving carboxylic acid/transamination reactions (e.g. glutamate oxaloacetate transaminase 1 (GOT1), glutamic pyruvate-alanine transaminase 2 (GPT2), cystathionase and redox proteins such as cytochrome b5 reductase 1 and ferredoxin reductase. Counter-intuitively, the data show reduction of mRNA in glycolytic processes [DAVID enrichment score 9.96 p value 1.90E-19], some corroborated by Western Blot, bringing in to question the sources of lactate observed in the presence of MPP+. Examining this aspect, the data show that diverse carboxylic acids (succinate, oxaloacetate and a-ketoglutarate) are capable of contributing to the lactate pool in addition to phosph(enolpyruvate) or pyruvate in the absence of glucose by this cell line. In conclusion, these findings show that MPP+ negatively affects the transcriptome involved with complex I, but initiated an elevation of G protein signaling and anaerobic metabolic systems involved with nitrogen/carboxylic acid metabolism. Future research will be required to elucidate the survival pathways that drive anaerobic substrate level phosphorylation, and define functional ramification to the loss of mitochondrial FAM162a and BNIP3 proteins. PMID- 22776089 TI - Complement receptor-3 negatively regulates the phagocytosis of degenerated myelin through tyrosine kinase Syk and cofilin. AB - BACKGROUND: Intact myelin, which normally surrounds axons, breaks down in Wallerian degeneration following axonal injury and during neurodegenerative diseases such as multiple sclerosis. Clearance of degenerated myelin by phagocytosis is essential since myelin impedes repair and exacerbates damage. CR3 (complement receptor-3) is a principal phagocytic receptor in myelin phagocytosis. We studied how tyrosine kinase Syk (spleen tyrosine kinase) and cofilin control phagocytosis of degenerated myelin by CR3 in microglia and macrophages. Syk is a non-receptor tyrosine kinase that CR3 recruits to convey cellular functions. Cofilin is an actin-depolymerizing protein that controls F actin (filamentous actin) remodeling (i.e., disassembly and reassembly) by shifting between active unphosphorylated and inactive phosphorylated states. RESULTS: Syk was continuously activated during prolonged phagocytosis. Phagocytosis increased when Syk activity and expression were reduced, suggesting that normally Syk down regulates CR3-mediated myelin phagocytosis. Levels of inactive p-cofilin (phosphorylated cofilin) decreased transiently during prolonged phagocytosis. In contrast, p-cofilin levels decreased continuously when Syk activity and expression were continuously reduced, suggesting that normally Syk advances the inactive state of cofilin. Observations also revealed inverse relationships between levels of phagocytosis and levels of inactive p-cofilin, suggesting that active unphosphorylated cofilin advances phagocytosis. Active cofilin could advance phagocytosis by promoting F-actin remodeling, which supports the production of membrane protrusions (e.g., filopodia), which, as we also revealed, are instrumental in myelin phagocytosis. CONCLUSIONS: CR3 both activates and downregulates myelin phagocytosis at the same time. Activation was previously documented. We presently demonstrate that downregulation is mediated through Syk, which advances the inactive phosphorylated state of cofilin. Self negative control of phagocytosis by the phagocytic receptor can be useful in protecting phagocytes from excessive phagocytosis (i.e., "overeating") during extended exposure to particles that are destined for ingestion. PMID- 22776090 TI - Molecular regulation of seed and fruit set. AB - Seed and fruit set are established during and soon after fertilization and determine seed and fruit number, their final size and, hence, yield potential. These processes are highly sensitive to biotic and abiotic stresses, which often lead to seed and fruit abortion. Here, we review the regulation of assimilate partitioning, including the potential roles of recently identified sucrose efflux transporters in seed and fruit set and examine the similarities of sucrose import and hydrolysis for both pollen and ovary sinks, and similar causes of abortion. We also discuss the molecular origins of parthenocarpy and the central roles of auxins and gibberellins in fruit set. The recently completed strawberry (Fragaria vesca) and tomato (Solanum lycopersicum) genomes have added to the existing crop databases, and new models are starting to be used in fruit and seed set studies. PMID- 22776091 TI - Nonenzymatic release of free reducing glycans from glycosphingolipids. AB - A major limitation in studying the structures and functions of glycans in glycosphingolipids is the difficulty in releasing free glycans for analysis and derivatization. Here we show that reducing glycans can be released nonenzymatically from glycosphingolipids after a brief treatment with ozone followed by heating in neutral aqueous buffer (pHs 6.0-8.0). The released free reducing glycans are then available for glycomic analyses, including fluorescent labeling, permethylation, and mass spectrometry. This procedure is simple and highly efficient, with no base-catalyzed "peeling" reaction by-products observed. PMID- 22776092 TI - RNA extraction from human articular cartilage by chondrocyte isolation. AB - We report an optimized method for RNA extraction from human articular cartilage that does not require the use of specialized equipment or column purification. To maximize RNA yield while minimizing degradation and contamination, chondrocytes are isolated from the extracellular matrix and the traditional TRIzol protocol is modified to include two RNA-DNA-protein phase separations. We compared RNA extracted using this modified method with the traditional TRIzol method by spectrophotometry, Bioanalyzer, and real-time polymerase chain reaction (PCR). With the modified method, RNA recovery is increased by nearly 1MUg per 100mg of cartilage, and RNA integrity number (RIN) is improved from 2.0 to 7.5. PMID- 22776093 TI - High UV-A exposure from sunbeds. PMID- 22776094 TI - The SYK side of TLR4: signalling mechanisms in response to LPS and minimally oxidized LDL. AB - Spleen tyrosine kinase (SYK) is the best known for its involvement in immune receptor signalling, mediated by binding of SYK tandem Src-homology 2 domains to tandem phosphotyrosine in immunoreceptor tyrosine-based activation motifs (ITAMs). ITAM adaptors or ITAM-containing receptor tails mediate signalling from B- and T-cell receptors, Fc receptors and many C-type lectins, including dectin 1. Recent data point to constitutive binding of SYK to the cytoplasmic domain of toll-like receptor-4 (TLR4). This SYK-TLR4 binding increases upon TLR4 dimerization and phosphorylation, and SYK plays a prominent role in TLR4 signalling in response to LPS in neutrophils and monocytes. SYK also plays an important role in TLR4-mediated macrophage responses to minimally oxidized low density lipoprotein (mmLDL), which is a form of oxidized LDL relevant to development of human atherosclerosis. Interestingly, mmLDL-induced effects in macrophages, which occur via TLR4, are predominantly MyD88 independent. This unmasks the role of the SYK branch of TLR4 signalling, which mediates modest cytokine release via activation of AP-1 transcription and robust reactive oxygen species generation and cytoskeletal rearrangements. The latter results in extensive membrane ruffling and macropinocytosis, leading to lipoprotein uptake and foam cell formation, a hallmark of atherosclerotic lesions. Because inhibitors of SYK activity, such as fostamatinib, are in advanced clinical trials for rheumatoid arthritis and other autoimmune diseases, understanding the role of SYK in signalling via TLR4 is of immediate importance. This signalling pathway seems to be particularly important in TLR4 activation by host-derived, damage associated molecular pattern ligands, such as mmLDL, relevant to development of atherosclerosis and other chronic inflammatory diseases. PMID- 22776095 TI - Changes in pain and insulin-like growth factor 1 in fibromyalgia during exercise: the involvement of cerebrospinal inflammatory factors and neuropeptides. AB - INTRODUCTION: Fibromyalgia (FM) is characterized by chronic pain. Impaired growth hormone responses and reduced serum insulin-like growth factor 1 (IGF-1) are common in FM. The aim was to examine changes in serum IGF-1, cerebrospinal fluid (CSF), neuropeptides, and cytokines during aerobic exercise in FM patients. METHODS: In total, 49 patients (median age, 52 years) with FM were included in the study. They were randomized to either the moderate- to high-intensity Nordic Walking (NW) program (n = 26) or the supervised low-intensity walking (LIW) program (n = 23). Patients participated in blood tests before and after 15 weeks of aerobic exercise. Changes in serum levels of free IGF-1, pain rating on a 0- to 100-mm scale, pain threshold, and 6-minute walk test (6MWT) were examined. CSF, neuropeptides, matrix metalloproteinase 3 (MMP-3), and inflammatory cytokines were determined. Nonparametric tests were used for group comparisons and correlation analyses. RESULTS: Serum free IGF-1 levels did not change during 15 weeks of exercise between the two groups, although the 6MWT significantly improved in the NW group (p = 0.033) when compared with LIW. Pain did not significantly change in any of the groups, but tended to decrease (p = 0.052) over time in the total group. A tendency toward a correlation was noted between baseline IGF-1 and a decrease of pain in response to exercise (r = 0.278; p = 0.059). When adjusted for age, this tendency disappeared. The change in serum free IGF-1 correlated positively with an alteration in CSF substance P (SP) levels (rs = 0.495; p = 0.072), neuropeptide Y (NPY) (rs = 0.802; p = 0.001), and pain threshold (rs = 0.276; p = 0.058). Differing CSF SP levels correlated positively to a change in pain threshold (rs = 0.600; p = 0.023), whereas the shift in CSF MMP-3 inversely correlated with an altered pain threshold (rs = 0.569; p = 0.034). CONCLUSIONS: The baseline level of serum free IGF-1 did not change during high or low intensity of aerobic exercise. Changes in IGF-1 correlated positively with a variation in CSF SP, NPY, and pain threshold. These data indicate a beneficial role of IGF-1 during exercise in FM. PMID- 22776097 TI - OnabotulinumtoxinA for treatment of focal cancer pain after surgery and/or radiation. AB - OBJECTIVE: To report the relief from refractory focal post-radiation and/or postsurgical cancer pain after local treatment with onabotulinumtoxinA. SETTING AND DESIGN: We studied the effect of onabotulinumtoxinA in seven cancer patients who suffered from severe focal pain (visual analog scale >5) at the site of local surgery or radiotherapy or both. OnabotulinumtoxinA (20-100 units) was injected into the focal pain areas (skin or muscle or both). Five of seven patients were followed beyond 1 year (1.5-5 years) with repeat treatment. RESULTS: All seven patients reported a significant improvement in pain (mean drop in visual analog scale score of 5.1). They described their response on the patient global assessment as satisfactory (two patients) or very satisfactory (five patients). Six of seven patients found the pain relief associated with significant improvement in quality of life. One patient developed weakness of jaw muscles after bilateral masseter injection that was not observed during second injection (reduced dose). Improvements with treatment persisted with repeat injections during long-term follow-up (five patients). CONCLUSION: Local treatment with onabotulinumtoxinA can significantly reduce pain and improve quality of life in cancer patients suffering from pain in the area of surgery and radiation and was well tolerated in cancer patients. PMID- 22776096 TI - Dominant optic atrophy. AB - DEFINITION OF THE DISEASE: Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC) and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. EPIDEMIOLOGY: The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. CLINICAL DESCRIPTION: DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. AETIOLOGY: Two genes (OPA1, OPA3) encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8) are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7) are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. DIAGNOSIS: Patients are usually diagnosed during their early childhood, because of bilateral, mild, otherwise unexplained visual loss related to optic discs pallor or atrophy, and typically occurring in the context of a family history of DOA. Optical Coherence Tomography further discloses non-specific thinning of retinal nerve fiber layer, but a normal morphology of the photoreceptors layers. Abnormal visual evoked potentials and pattern ERG may also reflect the dysfunction of the RGCs and their axons. Molecular diagnosis is provided by the identification of a mutation in the OPA1 gene (75% of DOA patients) or in the OPA3 gene (1% of patients). PROGNOSIS: Visual loss in DOA may progress during puberty until adulthood, with very slow subsequent chronic progression in most of the cases. On the opposite, in DOA patients with associated extra-ocular features, the visual loss may be more severe over time. MANAGEMENT: To date, there is no preventative or curative treatment in DOA; severely visually impaired patients may benefit from low vision aids. Genetic counseling is commonly offered and patients are advised to avoid alcohol and tobacco consumption, as well as the use of medications that may interfere with mitochondrial metabolism. Gene and pharmacological therapies for DOA are currently under investigation. PMID- 22776098 TI - Structural analysis of trimeric phospholipase A2 neurotoxin from the Australian taipan snake venom. AB - Snake pre-synaptic neurotoxins endowed with phospholipase A(2) activity are potent inducers of paralysis through the specific disruption of the neuromuscular junction pre-synaptic membrane and represent a valuable tool for investigating neuronal degeneration and recovery. They have different structural complexity and a wide range of lethal potency and enzymatic activity, although they share a similar mechanism of action. Although no correlation has been reported between neurotoxicity and enzymatic activity, toxicity increases with structural complexity and phospholipase A(2) oligomers show 10-fold lower LD(50) values compared to their monomeric counterparts. To date, no structural study has been performed on multimeric SPANs with the aim of shedding light on the correlation between structural complexity and neurotoxicity. In the present study, we investigated the structure of taipoxin, a trimeric phospholipase A(2) neurotoxin, as well as that of its subunits, by X-ray crystallography and small angle X-ray scattering analysis. We present the high-resolution structure of two isoforms of the taipoxin beta subunit, which show no neurotoxic activity but enhance the activity of the other subunits in the complex. One isoform shows no structural change that could justify the lack of activity. The other displays three point mutations in critical positions for the catalytic activity. Moreover, we designed a model for the quaternary structure of taipoxin under physiological conditions, in which the three subunits are organized into a flat holotoxin with the substrate binding sockets exposed on the same side of the complex, which suggests a role for this interface in the toxin-membrane interaction. PMID- 22776100 TI - Beneficial effects of early pulsed dye laser therapy in individuals with infantile hemangiomas. PMID- 22776099 TI - Hypovitaminosis D and osteopenia/osteoporosis in a haemophilia population: a study in HCV/HIV or HCV infected patients. AB - Recent reports show a correlation between haemophilia and osteoporosis. HIV, HCV and their treatments are independently associated with an increased risk of osteoporosis. Vitamin D plays a pivotal role in bone mineralization. The aim of our study was to compare Vitamin D levels, bone metabolism markers and bone mineral density (BMD) in patients with haemophilia with or without co-infections. Seventy-eight adult patients with severe or moderate haemophilia A or B were subdivided into three groups of 26 patients each (HIV-HCV co-infected, HCV mono infected and uninfected). The BMD was measured by dual energy X-ray absorptiometry (DXA) at both the femoral area (F) and lumbar spine (L). This was correlated to laboratory values and haemophilic arthropathy was assessed using validated clinical and radiological scores. The DXA showed a homogeneous F-BMD reduction in all the three groups, whereas L-BMD was significantly lower in co infected patients (P < 0.05). The clinical score was higher in co-infected (P < 0.002) and mono-infected (P < 0.006). The radiological score was higher in mono infected than in the other two groups (P < 0.001). Overall 25-hydroxyvitamin D (25-OH Vit D) was reduced (87%). Bone-specific alkaline phosphatase (b-ALP) and telopeptide were increased in co-infected (P < 0.001 and P < 0.01) and mono infected (P < 0.001 and P < 0.02). The result of the homogeneous F-BMD reduction in all groups could be explained by the pivotal role of arthropathy; the lower L BMD in co-infected and the increase of b-ALP and telopeptide in co-infected and mono-infected groups suggest faster bone metabolism in case of infections. PMID- 22776101 TI - Systematic review of the management of ischaemic colitis. AB - AIM: The study reviews the literature related to ischaemic colitis (IC) to establish an evidence base for its management and to identify factors predicting severity and mortality. METHOD: A systematic review of the English language literature was conducted according to recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. MEDLINE, Embase and Cochrane Library databases were searched using the keyword search 'ischaemic colitis OR colon ischaemia OR colonic ischaemia OR management ischaemic colitis'. IC is often misdiagnosed so only studies where the diagnosis was supported by histopathology in every case were included. Critical appraisal was performed of included studies using predefined quality assessment checklists and narrative data synthesis. RESULTS: In all, 2610 publications were identified. Of these, eight retrospective case series and three case controlled studies describing 1049 patients were included. Medical management was used in 80.3% patients of whom 6.2% died. Surgery was required in 19.6% of whom 39.3% died. The overall mortality of IC was 12.7%. Lack of rectal bleeding, peritonism and renal dysfunction were commonly quoted predictors of severity; however, right sided IC appeared to be the most significant predictor of outcome. CONCLUSION: Most patients with IC can be managed conservatively. Right sided IC may be the most significant predictor of severity. PMID- 22776103 TI - Improving outcomes of preschool language delay in the community: protocol for the Language for Learning randomised controlled trial. AB - BACKGROUND: Early language delay is a high-prevalence condition of concern to parents and professionals. It may result in lifelong deficits not only in language function, but also in social, emotional/behavioural, academic and economic well-being. Such delays can lead to considerable costs to the individual, the family and to society more widely. The Language for Learning trial tests a population-based intervention in 4 year olds with measured language delay, to determine (1) if it improves language and associated outcomes at ages 5 and 6 years and (2) its cost-effectiveness for families and the health care system. METHODS/DESIGN: A large-scale randomised trial of a year-long intervention targeting preschoolers with language delay, nested within a well documented, prospective, population-based cohort of 1464 children in Melbourne, Australia. All children received a 1.25-1.5 hour formal language assessment at their 4th birthday. The 200 children with expressive and/or receptive language scores more than 1.25 standard deviations below the mean were randomised into intervention or 'usual care' control arms. The 20-session intervention program comprises 18 one-hour home-based therapeutic sessions in three 6-week blocks, an outcome assessment, and a final feed-back/forward planning session. The therapy utilises a 'step up-step down' therapeutic approach depending on the child's language profile, severity and progress, with standardised, manualised activities covering the four language development domains of: vocabulary and grammar; narrative skills; comprehension monitoring; and phonological awareness/pre literacy skills. Blinded follow-up assessments at ages 5 and 6 years measure the primary outcome of receptive and expressive language, and secondary outcomes of vocabulary, narrative, and phonological skills. DISCUSSION: A key strength of this robust study is the implementation of a therapeutic framework that provides a standardised yet tailored approach for each child, with a focus on specific language domains known to be associated with later language and literacy. The trial responds to identified evidence gaps, has outcomes of direct relevance to families and the community, includes a well-developed economic analysis, and has the potential to improve long-term consequences of early language delay within a public health framework. TRIAL REGISTRATION: Current Controlled Trials ISRCTN03981121. PMID- 22776102 TI - Associations between demographic, disease related, and treatment pathway related variables and health related quality of life in primary care patients with coronary heart disease. AB - BACKGROUND: Coronary heart disease (CHD) is a common medical problem worldwide that demands shared care of general practitioners and cardiologists for concerned patients. In order to improve the cooperation between both medical specialists and to optimize evidence-based care, a treatment pathway for patients with CHD was developed and evaluated in a feasibility study according to the recommendation for the development and evaluation of complex interventions of the British Medical Research Council (MRC). In the context of this feasibility study the objective of the present research was to investigate the contributions of different disease related (e.g. prior myocardial infarction), pathway related (e.g. basic medication) and demographic variables on patients' perceived health related quality of life (HRQoL) as a relevant and widely used outcome measure in cardiac populations. METHODS: Data assessing demographic, disease and pathway related variables of CHD patients included in the study were collected in a quasi experimental design with three study arms (pathway developers, users, control group) via case record forms and questionnaires at baseline and after 6 and 12 (intervention groups), and 9 months (control group), respectively after the initial implementation on GP level. Additionally, at the same measuring points the CHD patients participating in the study were interviewed by phone regarding their perceived HRQoL, measured with the EuroQol EQ-5D as an index-based health questionnaire. Due to the hierarchical structure of the data, we performed cross sectional and longitudinal linear mixed models to investigate the impact of disease related, pathway related and demographic variables on patients' perceived HRQoL. RESULTS: Of 334 initially recruited patients with CHD, a total of 290 were included in our analysis. This was an average 13.2% dropout rate from baseline assessment to the 12-month follow-up. At all assessment points, patients' HRQoL was associated with a variety of sociodemographic variables (e.g. gender, employment, education) in each study group, but there was no association with pathway related variables. In both cross-sectional and longitudinal analyses highest HRQoL values in patients were reported in the physician group that had developed the pathway. In the longitudinal analyses there were no significant changes in the reported HRQoL values of the three groups over time. CONCLUSIONS: The found associations between sociodemographic variables and the perceived HRQoL of patients with CHD are in line with other research. As there are no associations of HRQoL with pathway related variables like the basic medication, possible weaknesses in the study design or the choice of outcome have to be considered before planning and conducting an evaluation study according to the MRC recommendations. Additionally, as patients in the developer group reported the highest HRQoL values over time, a higher commitment of the GPs in the developer group can be assumed and should be considered in further research. PMID- 22776104 TI - Effect of subinihibitory and inhibitory concentrations of Plectranthus amboinicus (Lour.) Spreng essential oil on Klebsiella pneumoniae. AB - We evaluated the antimicrobial activity and some mechanisms used by subinhibitory and inhibitory concentrations of the essential oil, obtained from leaves of Plectranthus amboinicus, against a standard strain of Klebsiella pneumoniae and 5 multiresistant clinical isolates of the bacteria. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), the rate of kill and the pH sensitivity of the essential oil were determined by microdilution tests performed in 96-well plates. Subinhibitory and inhibitory concentrations of the essential oil were tested in order to check its action on K. pneumoniae membrane permeability, capsule expression, urease activity and cell morphology. The MIC and MBC of the essential oil were 0.09+/-0.01%. A complete inhibition of the bacterial growth was observed after 2 h of incubation with twice the MIC of the essential oil. A better MIC was found when neutral or alkaline pH broth was used. Alteration in membrane permeability was found by the increase of crystal violet uptake when the bacteria were incubated with twice the MIC levels of the essential oil. The urease activity could be prevented when all the subinhibitory concentrations were tested in comparison to the untreated group (p<0.001). Alteration of the bacterial morphology besides inhibition of the capsule expression was verified by atomic force microscopy, and Anthony's stain method, respectively. Our data allow us to conclude that the essential oil of P. amboinicus can be a good candidate for future research. PMID- 22776105 TI - Climate warming and the decline of Taxus airborne pollen in urban pollen rain (Emilia Romagna, northern Italy). AB - Woody plant performance in a changing global environment has always been at the centre of palaeoenvironmental and long-term climate reconstructions carried out by means of pollen analysis. In Mediterranean regions, Taxus constitutes the highest percentage in past pollen diagrams from cold or cool periods, and therefore it is generally considered a good index to infer climate features from past records. However, a comparison of these inferences with the true current trends in pollen production has not been attemped until now. This study reports the decline of airborne pollen of Taxus observed in Emilia Romagna, a region of northern Italy, during the period 1990-2007. Phenological observations on four male specimens and microscopic examination of fresh pollen were made in order to check Taxus flowering time and pollen morphology. Airborne pollen was monitored through continuous sampling with a Hirst volumetric sampler. In the 18-year long period of investigation, Taxus pollen production has decreased, while total woody pollen abundance in air has increased. The trend of the Taxus pollen season shows a delay at the beginning, a shortening of the pollen period, and an advance of the end of the pollen season. This was interpreted as a response to climate warming. In particular, Taxus follows the behaviour of winter-flowering plants, and therefore earlier pollination is favoured at low autumn temperatures, while late pollination occurs more often, most likely after warm autumn temperatures. PMID- 22776106 TI - Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up. AB - BACKGROUND: Expression of inflammatory cytokines in cerebrospinal fluid (CSF) has led to the hypothesis of intrathecal chronic inflammation to explain the denervation observed in post-polio syndrome (PPS). It has been shown that therapy with intravenous immunoglobulin (IVIG) improves physical performance and dampens down the inflammatory process at 6 months in PPS patients. We here examined the effects of IVIG on cytokine expression and clinical outcome one year after IVIG treatment. METHODS: From a previous study with 135 PPS patients included, 41 patients were further evaluated before un-blinding for one year (21 placebo and 20 treated with IVIG, Xepol(r) 50 mg/ml), and were assessed for clinical variables by performing the Short Form-36 survey (SF-36) questionnaire assessment, the 6 minute walk distance test (6MWT) and registering pain level by Visual Analogue Scale (VAS) after IVIG treatment. A separate cohort of 37 PPS patients went through lumbar puncture (LP) at baseline and 20 patients, treated with IVIG, repeated the LP one year later. Thirty patients affected with other neurological diseases (OND) were used as control group. Inflammatory cytokines TNF, TGFbeta, IFNgamma, IL-23, IL-13 and IL-10 were measured in blood cells and CSF cells with RT-PCR. RESULTS: Scores of the physical components of SF-36 were significantly higher at the one year follow up time-point in the IVIG-treated patients when compared to baseline as well as to the control subjects. Pain VAS score and 6MWT improved significantly in the IVIG-treated patients when compared with baseline Relative expression of TNF and IFN-gamma in both PBMCs and CSF from PPS patients were increased compared to OND subjects at baseline (p < 0.05). One year after IVIG-treatment a decreased expression of IFN-gamma and IL23 was found in CSF of PPS patients, while anti-inflammatory IL-13 was increased (p < 0.05). CONCLUSIONS: IVIG has effects on relevant QoL variables and inflammatory cytokines up to one year in patients with PPS. This gives a basis for scheduling IVIG in upcoming trials with this therapy. PMID- 22776108 TI - Association between occlusal curvature and food comminution and mixing in human young adults with permanent dentitions. AB - OBJECTIVE: Occlusal curvatures in human adult dentition such as the curve of Spee, curve of Wilson and Monsons's sphere provide clinical guidance for prosthetic rehabilitation and orthodontic treatment. However, association between occlusal curvature and masticatory function is not known. The aim of this study was to investigate the association between occlusal curvature and food comminuting and food mixing ability in human young adults with permanent dentitions. DESIGN: Fifty young adults with complete dentitions (mean age, 25.0 years) participated in the study. Occlusal curvature was determined by a three dimensional analysis of the mandibular arch according to the Broadrick flag method. Food comminuting ability was assessed using a masticatory performance test with peanuts as test food and it was scored as median particle size. Food mixing ability was assessed using a mixing ability test with a two-coloured wax cube and it was scored as mixing ability index. RESULTS: A linear regression analysis identified the sphere radius of occlusal curvature as significant predictor for both median particle size and mixing ability index after controlling for maximum bite force (P<0.001). These results indicated that subjects with a flatter curvature (larger sphere) in the mandibular arch showed better food comminuting and mixing ability. Coefficient of determination (R(2)) of occlusal curvature related to median particle size and mixing ability index was comparable to that of maximum bite force. CONCLUSION: Occlusal curvature seems to be associated with food comminuting and mixing ability in human young adults with permanent dentitions. PMID- 22776107 TI - Variation in the ITS-1 and ITS-2 rRNA genomic regions of Cytauxzoon felis from bobcats and pumas in the eastern United States and comparison with sequences from domestic cats. AB - Cytauxzoon felis, a tick-borne protozoan parasite, is the causative agent of cytauxzoonosis in domestic cats in the United States. The natural reservoir for this parasite is the bobcat (Lynx rufus), which typically does not develop clinical signs. Although not likely important reservoirs, C. felis has also been detected in pumas (Puma concolor) in Florida and Louisiana. Recent studies suggest that specific genotypes of C. felis that circulate in domestic cats may be associated with variable clinical outcomes and specific spatial locations. In the current study, we investigated the intraspecific variation of the C. felis internal transcribed spacer (ITS)-1 and ITS-2 rRNA regions from 145 wild felids (139 bobcats and six pumas) from 11 states (Florida, Georgia, Kansas, Kentucky, Louisiana, Missouri, North Carolina, North Dakota, South Carolina, Oklahoma, and Pennsylvania). Unambiguous ITS-1 and ITS-2 data were obtained for 144 and 112 samples, respectively, and both ITS-1 and ITS-2 sequences were obtained for 111 (77%) samples. For the ITS-1 region, sequences from 65 samples collected from wild felids were identical to those previously reported in domestic cats, while the other 79 sequences were unique. C. felis from 45 bobcats and one puma had ITS 1 sequences identical to the most common sequence reported from domestic cats. Within the ITS-2 region, sequences from 49 bobcats were identical to those previously reported in domestic cats and 63 sequences were unique (with some occurring in more than one bobcat). The most common ITS-2 sequence from domestic cats was also common in wild felids (31 bobcats and a puma). Samples from three pumas from Florida and two bobcats from Missouri had a 40- or 41-bp insert in the ITS-2 similar to one described previously in a domestic cat from Arkansas. Additionally, a previously undescribed 198- or 199-bp insert was detected in the ITS-2 sequence from four bobcats. Collectively, based on combined ITS-1 and ITS-2 sequences, five different genotypes were detected in the wild felids. Genotype ITSa was the most common genotype (11 bobcats and one puma) and fewer numbers of ITSb, ITSe, ITSg, and ITSi were detected in bobcats. These data indicate that, based on ITS-1 and ITS-2 sequences, numerous C. felis strains may circulate in wild felids. PMID- 22776109 TI - Apigenin prevents deregulation in the expression pattern of cell-proliferative, apoptotic, inflammatory and angiogenic markers during 7,12 dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. AB - OBJECTIVE: Malignant tumour arises due to abnormal cell proliferation, chronic inflammation, defect in apoptotic pathway and unwanted angiogenesis. The present study has investigated the modulating effect of apigenin on expression pattern of apoptotic (p53, Bcl-2, Bax, Caspase-3 and 9) cell proliferative (PCNA, Cyclin D1, c-fos), angiogenic (VEGF) and inflammatory (NFkappaB, COX-2) markers during 7,12 dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. MATERIALS AND METHODS: Oral squamous cell carcinoma was developed in the buccal pouches of golden Syrian hamsters by painting with 0.5% DMBA three times a week for 14 weeks. Deregulation in the expression of the cell proliferation, apoptosis, inflammation and angiogenesis markers was noticed in hamsters treated with DMBA alone. RESULTS: Oral administration of apigenin at a dose of 2.5mg/kgbw prevented the deregulation of the above mentioned molecular markers in hamsters treated with DMBA. CONCLUSION: Our results thus suggest that apigenin exhibited anti-cell proliferative, anti-inflammatory, anti-angiogenic and apoptotic potential during DMBA-induced hamster buccal pouch carcinogenesis. PMID- 22776111 TI - Sub-viral imaging of vaccinia virus using super-resolution microscopy. AB - The study of host-pathogen interactions over past decades has benefited from advances in microscopy and fluorescent imaging techniques. A particularly powerful model in this field is vaccinia virus (VACV), which due to its amenability to genetic manipulation has been a productive model in advancing the understanding of the transport of subcellular cargoes. Conventional light microscopy imposes an upper limit of resolution of ~250nm, hence knowledge of events occurring at the sub-viral resolution is based predominantly on studies utilising electron microscopy. The development of super-resolution light microscopy presents the opportunity to bridge the gap between these two technologies. This report describes the analysis of VACV replication using fluorescent recombinant viruses, achieving sub-viral resolution with three dimensional structured illumination microscopy. This is the first report of successfully resolving poxvirus particle morphologies at the scale of single virus particles using light microscopy. PMID- 22776110 TI - Histone modification pattern evolution after yeast gene duplication. AB - BACKGROUND: Gene duplication and subsequent functional divergence especially expression divergence have been widely considered as main sources for evolutionary innovations. Many studies evidenced that genetic regulatory network evolved rapidly shortly after gene duplication, thus leading to accelerated expression divergence and diversification. However, little is known whether epigenetic factors have mediated the evolution of expression regulation since gene duplication. In this study, we conducted detailed analyses on yeast histone modification (HM), the major epigenetics type in this organism, as well as other available functional genomics data to address this issue. RESULTS: Duplicate genes, on average, share more common HM-code patterns than random singleton pairs in their promoters and open reading frames (ORF). Though HM-code divergence between duplicates in both promoter and ORF regions increase with their sequence divergence, the HM-code in ORF region evolves slower than that in promoter region, probably owing to the functional constraints imposed on protein sequences. After excluding the confounding effect of sequence divergence (or evolutionary time), we found the evidence supporting the notion that in yeast, the HM-code may co-evolve with cis- and trans-regulatory factors. Moreover, we observed that deletion of some yeast HM-related enzymes increases the expression divergence between duplicate genes, yet the effect is lower than the case of transcription factor (TF) deletion or environmental stresses. CONCLUSIONS: Our analyses demonstrate that after gene duplication, yeast histone modification profile between duplicates diverged with evolutionary time, similar to genetic regulatory elements. Moreover, we found the evidence of the co-evolution between genetic and epigenetic elements since gene duplication, together contributing to the expression divergence between duplicate genes. PMID- 22776112 TI - Changes in blood parameters and the expression of coagulation-related genes in lactating Sprague-Dawley rats. AB - This study measured blood parameters, particularly those related to coagulation, and alterations in the expression levels of blood-coagulation-related genes in lactating Sprague-Dawley rats. The day of delivery was designated as lactation day 0 (LD 0). On the day after delivery (LD 1), prothrombin time and overall activity of vitamin-K-dependent coagulation factors were decreased, whereas fibrinogen contents, platelet counts and antithrombin III concentrations were increased as compared with those in nonpregnant rats. In addition, hepatic expression of blood-coagulation-related genes in the liver was increased at LD 0 as compared with that in nonpregnant rats. These changes may be physiologic responses to prevent prolonged bleeding at delivery. Except for fibrinogen content, which remained elevated, the described changes returned to baseline on and after LD 7. Activities of AST, ALT, and ALP were increased on LD 7, 14, and 21 as compared with nonpregnant rats. In contrast, total protein, albumin, Cl, and Ca were consistently lower on LD 7, 14, or 21 as compared with levels in nonpregnant rats. These results provide background data for evaluation of nursing rats. PMID- 22776113 TI - Normal hematologic and serum biochemical values of cotton-top tamarins (Saguinus oedipus). AB - We obtained whole-blood hematologic and serum biochemical values from 38 captive bred cotton-top tamarins (Saguinus oedipus). Data were analyzed to determine the effect of sex on blood parameters. Significant differences between either the means or medians of male and female tamarins were found for creatinine, hematocrit, hemoglobin, RBC count, and PCV. These results establish baseline hematologic and serum biochemical values and provide a useful resource not previously available in the peer-reviewed literature for the clinical care of cotton-top tamarins, a critically endangered New World primate, in a captive setting. PMID- 22776114 TI - Carbon dioxide and oxygen levels in disposable individually ventilated cages after removal from mechanical ventilation. AB - Disposable individually ventilated cages have lids that restrict air exchange when the cage is not mechanically ventilated. This design feature may cause intracage CO2 to increase and O2 to decrease (hypercapnic and hypoxic conditions, respectively) when the electrical supply to the ventilated rack fails, the ventilated rack malfunctions, cages are docked in the rack incorrectly, or cages are removed from the ventilated rack for extended periods of time. We investigated how quickly hypercapnic and hypoxic conditions developed within disposable individually ventilated cages after removal from mechanical ventilation and compared the data with nondisposable static cages, disposable static cages, and unventilated nondisposable individually ventilated cages. When disposable individually ventilated cages with 5 adult mice per cage were removed from mechanical ventilation, CO2 concentrations increased from less than 1% at 0 h to approximately 5% at 3 h and O2 levels dropped from more than 20% at 0 h to 11.7% at 6 h. The breathing pattern of the mice showed a prominent abdominal component (hyperventilation). Changes were similar for 4 adult mice per cage, reaching at least 5% CO2 at 4 h and 13.0% O2 at 6 h. For 3 or 2 mice per cage, values were 4.6% CO2 and 14.7% O2 and 3.04% CO2 and 17.1% O2, respectively, at 6 h. These results document that within disposable individually ventilated cages, a hypercapnic and hypoxic microenvironment develops within hours in the absence of mechanical ventilation. PMID- 22776115 TI - Processing and treatment of corncob bedding affects cage-change frequency for C57BL/6 mice. AB - The goal of this study was to evaluate the effectiveness of a new proprietary processed corncob bedding material (PCC)compared with standard corncob in ventilated and static mouse housing systems. Intracage ammonia levels, bacterial growth, and absorptive capacity of bedding were measured for cages of C57BL/6 mice under nonautoclaved and autoclaved conditions on static and ventilated racks in a barrier facility. Ammonia concentration was measured daily, and cages were removed from the study when measurements reached or exceeded 25 ppm. Bacterial growth in bedding was quantified and speciated before exposure to mice and at the time of cage removal. The absorptive capacity of all bedding material was determined under autoclaved and nonautoclaved conditions. Ventilated cages with PCC or autoclaved corncob took longer to reach ammonia concentrations of 25 ppm than did those with corncob or autoclaved PCC; PCC-filled cages remained below 25 ppm NH3 for at least 3 wk. The type of bedding material did not affect the number of days required to reach 25 ppm in static cages. Compared with other bedding types in the absence of mice, 1/4-in. PCC had a lower and 1/8-in. corncob a higher bacterial load. Autoclaving altered the absorptive capacity of 1/4-in. bedding materials, and for 1/8-in. bedding, corncob was more absorptive than PCC regardless of autoclaving. The results of this study indicate that PCC is comparable to autoclaved corncob in controlling intracage ammonia levels, and a cage-change interval of 3 wk is possible when ventilated cages are used with this bedding. PMID- 22776116 TI - The effect of different working definitions on behavioral research involving stereotypies in Mongolian gerbils (Meriones unguiculatus). AB - Many sources of variation in animal experiments are related to characteristics of the animal or its husbandry conditions. In ethologic studies, observational methods can also affect interexperimental variation. Different descriptions for a behavior can lead to divergent findings that may be incorrectly attributed to other factors if not recognized as stemming from a classification dissonance. Here we discuss 2 observational studies in Mongolian gerbils (Meriones unguiculatus). The first study describes how data vary when 2 different working definitions are used for stereotypic digging: WD(mor), a definition based on a morphologic description of the behavior, and WD(12), a definition that relies mainly on a duration criterion of digging bouts (greater than 12 s). The total duration and number of stereotypic bouts were 22.0% and 63.1% lower, respectively, when WD(12) was applied compared with WD(mor). However, strong correlations existed between data generated by WD(mor) and WD(12), indicating that the 2 definitions yielded qualitatively similar results. The second study provides the first report that laboratory gerbils develop stereotypic behavior that is characterized by alternating bouts of digging and bar-gnawing. Of the 1685 stereotypy bouts investigated, 9.1% comprised both stereotypies, 87.6% consisted of digging only, and 3.3% consisted of bar gnawing only. Working definitions that neglect combined stereotypies can result in considerable underestimation of stereotypic behavior in Mongolian gerbils. PMID- 22776117 TI - Mouse housing system using pressurized cages intraventilated by direct-current microfans. AB - We performed the initial assessment of an alternative pressurized intraventilated (PIV) caging system for laboratory mice that uses direct-current microfans to achieve cage pressurization and ventilation. Twenty-nine pairs of female SPF BALB/c mice were used, with 19 experimental pairs kept in PIV cages and 10 control pairs kept in regular filter-top (FT) cages. Both groups were housed in a standard housing room with a conventional atmospheric control system. For both systems, intracage temperatures were in equilibrium with ambient room temperature. PIV cages showed a significant difference in pressure between days 1 and 8. Air speed (and consequently airflow rate) and the number of air changes hourly in the PIV cages showed decreasing trends. In both systems, ammonia concentrations increased with time, with significant differences between groups starting on day 1. Overall, the data revealed that intracage pressurization and ventilation by using microfans is a simple, reliable system, with low cost, maintenance requirements, and incidence of failures. Further experiments are needed to determine the potential influence of this system on the reproductive performance and pulmonary integrity in mice. PMID- 22776118 TI - Effectiveness of shoe covers for bioexclusion within an animal facility. AB - The personal protective equipment (PPE) required for entry into rodent barrier rooms often includes a hair bonnet, face mask, disposable gown, gloves, and shoe covers. Traditionally, shoe covers have been considered essential PPE for maintaining a 'clean' animal room. The introduction of microisolation caging and ventilated rack housing prompted us to reevaluate the contribution of shoe covers to bioexclusion. Contamination powder that fluoresces under black light was to track particle dispersal on the floor and personnel. The test mouse room contained a ventilated microisolation rack and biosafety cabinet. Powder was applied directly inside or outside the animal room doorway. PPE with or without shoe covers was donned outside of the animal room doorway and discarded on exiting. Participants either were scanned on entry into the room for the presence of florescence or asked to complete a simulated standard animal room activity while wearing full PPE. Animal rooms were scanned for florescence after exit of participants. All participants donning shoe covers fluoresced in multiple areas, primarily on gloves and gowns. Shoe covers had no effect on the spread of powder in normal traffic patterns, with no powder detected within caging. Powder also was used to determine the distance substances could be carried on the floor from building entry points. Results indicate that shoe covers do not improve (and actually may compromise) bioexclusion. Donning of shoe covers offers a potential for contamination of personnel from contact with shoe bottoms. PMID- 22776119 TI - Corynebacterium bovis: epizootiologic features and environmental contamination in an enzootically infected rodent room. AB - Corynebacterium bovis is a common pathogen in athymic nude mouse colonies. Control and eradication of the organism are challenging because depopulation and restricted colony access are often not options within vivaria. We evaluated potential sources and dissemination routes of C. bovis in an enzootically infected colony. Immunocompetent mice and personnel were evaluated for their potential to carry C. bovis, and husbandry and sanitation methods were evaluated for their efficacy in preventing cross-contamination. C. bovis was detected in furred immunocompetent mice previously exposed to infected athymic nude mice and in the nasopharynx of humans. Microisolation cages were not effective in maintaining athymic nude mice C. bovis-free when they were housed in a room known to contain immunodeficient mice with C. bovis infections. A tunnel washer that provided a >=180 degrees F final rinse provided effective elimination of C. bovis from cage components. Passive and active air sampling techniques showed airborne dispersal of C. bovis despite the use of individually ventilated caging systems and stringent operational standards. Bacterial growth was not observed in settle plates placed inside autoclaved individually ventilated microisolation cages on various ventilated racks for 24-h periods. C. bovis aerosolization was shown to be a means of spread of the bacterium during cage-change procedures inside a class II type A2 biosafety cabinet. Our findings indicate that C. bovis can be a pervasive environmental contaminant in infected rodent holding rooms and successful eradication strategies must include environmental decontamination and attention to air quality. PMID- 22776122 TI - Voluntary ingestion of antiparasitic drugs emulsified in honey represents an alternative to gavage in mice. AB - The oral route is the most frequently used method of drug intake in humans. Oral administration of drugs to laboratory animals such as mice typically is achieved through gavage, in which a feeding needle is introduced into the esophagus and the drug is delivered directly into the stomach. This method requires technical skill, is stressful for animals, and introduces risk of injury, pain and morbidity. Here we investigated another method of drug administration. The benzimidazole derivative albendazole was emulsified in commercially available honey and administered to mice by voluntary feeding or gavage. Mice that received albendazole by either gavage or honey ingestion had virtually identical levels of serum albendazole sulfoxide, indicating that uptake and metabolism of albendazole was similar for both administration techniques. In addition, dosing mice with the albendazole-honey mixture for 8 wk had antiparasitic activity comparable to earlier studies using gavage for drug administration. Compared with gavage, voluntary ingestion of a drug in honey is more rapid, less stressful to the animal, and less technically demanding for the administrator. Because of its low cost and ready availability, honey presents a viable vehicle for drug delivery. PMID- 22776120 TI - Total IgE as a serodiagnostic marker to aid murine fur mite detection. AB - Mites of 3 genera-Myobia, Myocoptes, and Radfordia -continue to plague laboratory mouse facilities, even with use of stringent biosecurity measures. Mites often spread before diagnosis, predominantly because of detection difficulty. Current detection methods have suboptimal sensitivity, are time-consuming, and are costly. A sensitive serodiagnostic technique would facilitate detection and ease workload. We evaluated whether total IgE increases could serve as a serodiagnostic marker to identify mite infestations. Variables affecting total IgE levels including infestation duration, sex, age, mite species, soiled-bedding exposure, and ivermectin treatment were investigated in Swiss Webster mice. Strain- and pinworm-associated effects were examined by using C57BL/6 mice and Swiss Webster mice dually infested with Syphacia obvelata and Aspiculuris tetraptera, respectively. Mite infestations led to significant increases in IgE levels within 2 to 4 wk. Total IgE threshold levels and corresponding sensitivity and specificity values were determined along the continuum of a receiver operating characteristic curve. A threshold of 81 ng/mL was chosen for Swiss Webster mice; values above this point should trigger screening by a secondary, more specific method. Sex-associated differences were not significant. Age, strain, and infecting parasite caused variability in IgE responses. Mice exposed to soiled bedding showed a delayed yet significant increase in total IgE. Treatment with ivermectin reduced total IgE levels within 2 wk. Our data suggest that increases in total IgE in Swiss Webster and C57BL/6 mice warrant investigation, especially because mite infestations can rapidly elevate total IgE levels. We propose that using total IgE levels routinely in serologic panels will enhance biosecurity. PMID- 22776121 TI - Combining sevoflurane anesthesia with fentanyl-midazolam or s-ketamine in laboratory mice. AB - Laboratory mice typically are anesthetized by either inhalation of volatile anesthetics or injection of drugs. Here we compared the acute and postanesthetic effects of combining both methods with standard inhalant monoanesthesia using sevoflurane in mice. After injection of fentanyl-midazolam or S-ketamine as premedication, a standard 50-min anesthesia was conducted by using sevoflurane. Addition of fentanyl-midazolam (0.04 mg/kg-4 mg/kg) induced sedation, attenuation of aversive behaviors at induction, shortening of the induction phase, and reduced the sevoflurane concentration required by one third (3.3% compared with 5%), compared with S-ketamine (30 mg/kg) premedication or sevoflurane alone. During anesthesia, heart rate and core body temperature were depressed significantly by both premedications but in general remained within normal ranges. In contrast, with or without premedication, substantial respiratory depression was evident, with a marked decline in respiratory rate accompanied by hypoxia, hypercapnia, and acidosis. Arrhythmia, apnea, and occasionally death occurred under S-ketamine-sevoflurane. Postanesthetic telemetric measurements showed unchanged locomotor activity but elevated heart rate and core body temperature at 12 h; these changes were most prominent during sevoflurane monoanesthesia and least pronounced or absent during fentanyl-midazolam sevoflurane. In conclusion, combining injectable and inhalant anesthetics in mice can be advantageous compared with inhalation monoanesthesia at induction and postanesthetically. However, adverse physiologic side effects during anesthesia can be exacerbated by premedications, requiring careful selection of drugs and dosages. PMID- 22776123 TI - Use of fenbendazole-containing therapeutic diets for mice in experimental cancer therapy studies. AB - Pinworm infection (oxyuriasis) is a common problem in rodent colonies. Facility wide prophylactic treatment of all mice with a diet containing therapeutic levels of fenbendazole for several weeks is often used to control pinworm outbreaks. We examined the effect of feeding a therapeutic diet containing 150 ppm fenbendazole on the growth of EMT6 mouse mammary tumors implanted into BALB/c Rw mice. Mice were randomized to receive either a fenbendazole-containing or control diet for 1 wk before tumor cells were injected intradermally in the flanks and throughout tumor growth. Tumor growth was monitored by serial measurements of tumor diameters from the time tumors became palpable until they reached 1000 mm3. The medicated diet did not alter tumor growth, invasion, or metastasis. When tumors reached volumes of approximately 100 mm3, some were irradiated locally with 10 Gy of X-rays. Irradiation significantly delayed tumor growth; fenbendazole did not alter the radiation-induced growth delay. However, cell culture studies showed that fenbendazole concentrations not far above those expected in the tissues of mice on this diet altered the growth of the tumor cells in culture. Recent data from other laboratories also have demonstrated effects of fenbendazole that could complicate experiments. Care should therefore be exercised in deciding whether chow containing fenbendazole should be administered to mouse colonies being used in cancer research. PMID- 22776124 TI - Simultaneous pulmonary and systemic blood pressure and ECG Interval measurement in conscious, freely moving rats. AB - Here we evaluated the ability of a new, dual blood-pressure telemetry transmitter to simultaneously measure pulmonary and systemic blood pressure and the electrocardiogram in rats. The transmitter was implanted in normotensive and monocrotaline-induced pulmonary hypertensive Wistar rats, with sensing catheters placed in the pulmonary artery (channel 1) and descending aorta (channel 2). Biopotential electrodes were positioned to record an apex-based lead II electrocardiogram. Pulmonary and systemic arterial blood pressure and electrocardiographic waveforms were recorded between 2 and 12 wk after implantation of the transmitter. During this period, pulmonary arterial pressure progressively increased in monocrotaline-treated compared with saline-treated rats. The pharmacologic response of rats to reference compounds was measured by using the transmitter to validate the technique and to evaluate the ability of the device to transmit changes in blood pressure and the electrocardiogram. Validation against 2 Millar high-fidelity blood-pressure catheters confirmed the accuracy of the blood pressure data recorded with the transmitter. In addition, local tolerance of the associated catheters was confirmed by histologic examination. PMID- 22776125 TI - Alternatives to retroorbital blood collection in hispid cotton rats (Sigmodon hispidus). AB - Cotton rats (Sigmodon hispidus) are a valuable animal model for many human viral diseases, including polio virus, measles virus, respiratory syncytial virus, and herpes simplex virus. Although cotton rats have been used in research since 1939, few publications address handling and sampling techniques for this species, and the retroorbital sinus remains the recommended blood sampling site. Here we assessed blood sampling methods that are currently used in other species and a novel subzygomatic sampling site for their use in S. hispidus. The subzygomatic approach accesses a venous sinus that possibly is unique to this species and that lies just below the zygomatic arch of the maxilla and deep to the masseter muscle. We report that both the novel subzygomatic approach and the sublingual vein method can be used effectively in cotton rats. PMID- 22776127 TI - Mortality and morbidity in African clawed frogs (Xenopus laevis) associated with construction noise and vibrations. AB - In Spring 2008, 175 adult female Xenopus laevis were exposed to construction related vibrations that caused overt water rippling in the frog tanks. The 3 affected tanks were custom-built static, 300-gal 'pond-style' tanks that sat on the floor of the housing room. The water in the tank developed visible ripples as a result of the vibrations transmitted through the floor during jack-hammering in an adjacent room that was approximately 10 ftaway. All frogs in the tanks displayed buoyancy problems, excessive air gulping, and skin sloughing; ultimately 7 frogs died. In addition, these 7 animals were bloated, and 5 of these 7 had regurgitated and everted their stomach and distal esophagus into the oral cavity, resulting in airway obstruction and death. Gross pathologic findings included regurgitation and eversion of the stomach of the distal portion of the esophagus into the oral cavity, obstruction of the airway, and lung overinflation. No significant histologic lesions were observed. Construction vibrations transmitted through the water appeared to have disrupted the mechanoreceptive function of the lateral line system, resulting in overstimulation of the noxious feeding response, regurgitation, and eversion of the stomach and distal esophagus into the oral cavity and subsequent suffocation due to airway obstruction. After immediate cessation of the jack-hammering and relocation of the remaining frogs, no additional morbidities or mortalities occurred. PMID- 22776126 TI - Effects of various anesthetic protocols on 18F-flurodeoxyglucose uptake into the brains and hearts of normal miniature pigs (Sus scrofa domestica). AB - This study used positron emission tomography-computed tomography (PET-CT) to evaluate the effects of 4 anesthetic protocols on 2-deoxy-2-[18F]-fluoro-D glucose (18F-FDG) accumulation in the brains and hearts of miniature pigs (Sus scrofa domestica). The 18F-FDG standard uptake value was quantified by dividing the brain into 6 regions: cerebellum, brainstem, and frontal, parietal, temporal, and occipital lobes. Five (2 female and 3 male) clinically normal miniature pigs were premedicated with medetomidine (200 MUg/kg IM) after which the following 4 anesthetic protocols were administered by using a crossover design: 1) propofol (4 mg/kg IV)-isoflurane inhalation; 2) propofol (4 mg/kg IV); 3) ketamine (5 mg/kg IV); 4) tiletamine-zolazepam (4.4 mg/kg IM). Compared with levels after other protocols, brain accumulation of 18F-FDG increased during propofol anesthesia but decreased with tiletamine-zolazepam. Relative to that due to other protocols, heart accumulation of 18F-FDG increased with propofol-isoflurane anesthesia but decreased with tiletamine-zolazepam. Comparing glucose accumulation in the brain and heart of miniature pigs by using PET-CT, we found that glucose accumulation varied according to the anesthetic protocol and between the 2 organs. These results can be used to evaluate how different anesthetic agents affect glucose metabolism in brain and heart of miniature pigs. Furthermore, these data should be considered when selecting an anesthetic agent for miniature pigs that will undergo PET-CT imaging with 18F-FDG. PMID- 22776128 TI - Characterization of newly established oral squamous cell carcinoma; 33-bp deletion in exons 3-4 of the p53 tumor suppressor gene. PMID- 22776129 TI - Prognostic value of the chemokine receptor CXCR4 and epithelial-to-mesenchymal transition in patients with squamous cell carcinoma of the mobile tongue. AB - OBJECTIVE: The aim of this study was to evaluate the expression and the prognostic value of chemokine receptor 4 (CXCR4), its cognate ligand the CXCL12, and markers of epithelial-to-mesenchymal transition (EMT) in squamous cell carcinoma (SCC) of the mobile tongue. PATIENTS AND METHODS: Patients with primary SCC of the mobile tongue who underwent surgery in our center were screened retrospectively. Patients without prior treatment, who had pre-surgery TNM staging and available tumor samples, were eligible. Protein expression of CXCL12, CXCR4, CA9, E-cadherin, and vimentin was determined by immunohistochemical staining, scored, and correlated with clinical and pathological parameters and overall survival. Multivariate and Cox proportional hazards analyses were performed. RESULTS: Among 160 patients treated and screened, 47 were analyzed. CXCR4 and CXCL12 expression was high in tumor cells. CXCR4 expression in primary tumor samples was significantly higher in patients with high-grade tumors, lymph node metastases, and microscopic nerve invasion (p <= 0.05). There was a non significant trend towards a correlation between high CXCL12 expression and pathologic tumor stage (p=0.07). Tumors with high CXCR4 expression correlated with poor overall survival (hazard ratio=3.6, 95% confidence interval 1.3-9.7; p=0.011), notably in the CXCR4(high)/vimentin-positive subgroup. Vimentin positive tumors, characterizing EMT, were associated with lower survival (hazard ratio=4.5, 95% confidence interval 1.6-12.3; p=0.0086). Multivariate analysis confirmed vimentin (but not CXCR4) expression as an independent prognostic factor of poor overall survival (p=0.016). CONCLUSION: Our results suggest that CXCR4 is a marker of tumor aggressiveness and vimentin is an important and independent prognostic factor in patients with SCC of the mobile tongue. PMID- 22776131 TI - The epidemic of oral cancer in India continues unabated: need for new policy initiatives. PMID- 22776130 TI - Polymorphism of angiotensin I-converting enzyme gene is related to oral cancer and lymph node metastasis in male betel quid chewers. AB - OBJECTIVES: Angiotensin I-converting enzyme (ACE), a type I cell surface zinc metallopeptidase, is differentially expressed in several malignancies and plays a role in tumor cell proliferation, tumor cell migration, angiogenesis, and metastatic behavior. We aimed to investigate the effects of ACE gene (rs1799752) variants on oral cancer risk. MATERIALS AND METHODS: Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) 32 was used to measure ACE gene polymorphisms in 88 patients with oral precancerous lesion (OPL), 186 33 patients with oral cancer, and 120 control subjects without any oral lesions. All study subjects were male 34 betel quid chewers. RESULTS: Patients with oral cancer or OPL had a higher frequency of the DD genotype than the control patients did. Oral cancer patients with the DD genotype had a significantly higher prevalence of lymph node metastases than patients with the II/ID genotype did. After adjusting for age, smoking, drinking, and betel quid chewing status, we found that individuals with the DD genotype of the ACE gene had a 5.46-fold and 3.13-fold higher risk of developing oral cancer or OPL, respectively, than those with the II genotype did. Furthermore, oral cancer patients with the DD genotype of the ACE gene had a 2.16-fold higher likelihood of lymph node metastasis. CONCLUSION: Our data suggest that the ACE gene polymorphisms may be associated with increased susceptibility to OPL and oral cancer and lymph node metastasis from oral cancer. PMID- 22776132 TI - Modulating cognitive deficits and tau accumulation in a mouse model of aging Down syndrome through neonatal implantation of neural progenitor cells. AB - Although Down syndrome (DS) is primarily considered as a pediatric disorder, all DS patients incur Alzheimer's disease (AD)-like pathology and about 60% develop an additional AD-like dementia by 30-40 years of age. Cognitive and neuroanatomical changes in DS are least compromised perinatally, indicating there may be an opportunity to modulate their cognitive and neuroanatomical development during aging, preventing or postponing the onset of AD. To this end, neural progenitor cells (NPC) or saline were implanted into the hippocampus of neonatal DS-modeling (trisomic Ts65Dn) mice and non-DS (disomic Ts65Dn) age-matched mice. Twelve months later, implanted and unimplanted mice were assessed for long-term survival of NPC, for cognitive function, hippocampal cell density, and the presence of extracellular tau accumulation. Implantation of NPC in trisomic mice improved learning and memory as assessed by conditioned taste aversion testing, but not on the novel object recognition task. Trisomic mice given saline control injections improved performance on both cognitive tasks compared to unimplanted trisomic mice. In contrast, disomic mice, implanted with either saline or NPC, were impaired in both tasks. Long-term surviving NPC were found in 7 out of 11 disomic brains and 4 out of 5 trisomic brains, with an average survival rate of 3.1% and 5.9% respectively. Extracellular tau aggregations were elevated in trisomic mice, but implantation with NPC was associated with significantly fewer aggregations. This was also seen in disomic mice. Saline injections significantly elevated tau presence in both karyotypes. Based on these results, we conclude that the modest effects of a few surviving NPC cannot be distinguished from those induced by the implant procedure. However, the changes prompted by neonatal treatment were detectable in aged animals. Collectively, our data are consistent with the hypothesis that neonatal therapeutic intervention in DS has the potential to exert positive lasting effects in the later stages of life but that NPC or the implantation approach may not be the most effective strategy and alternative stem cell types or delivery systems merit further investigation. PMID- 22776133 TI - Age-related differences in the effects of alpha and gamma peroxisome proliferator activated receptor subtype agonists on endothelial vasodilation in human microvessels. AB - Endothelial vasodilation in human vessels is impaired by aging and other cardiovascular risk factors (CVRF) but the differential impact of aging and CVRF in human endothelial function is not completely elucidated. The aim of this work was to evaluate the influence of aging on the effects of peroxisome proliferator activated receptor (PPAR)-alpha and -gamma subtype agonists on endothelium dependent vasodilation of isolated human vessels from subjects with or without CVRF. Human mesenteric microarteries were dissected from omentum specimens obtained from subjects younger or older than 60 years having or not CVRF and mounted in wire myographs to evaluate endothelium-dependent relaxation to bradykinin (BK). Aging and CVRF independently reduced endothelium-dependent relaxations. An additional impairment was produced when aging and CVRF co-existed (p<0.001). In vessels from adult subjects PPARgamma agonist, GW1929 (1 MUM) improved BK-induced responses only in those obtained from subjects with CVRF. By contrast, GW1929 improved the responses in vessels from elderly subjects having or not CVRF. PPARalpha agonist, GW7647 (1 MUM), enhanced endothelial vasodilation in adults with CVRF (p<0.001) but lack any effect in vessels from older subjects having or not CVRF. In vessels from subjects with CVRF, superoxide dismutase (SOD; 100 U/ml) improved BK-induced responses only in elderly subjects (p<0.001). Vascular aging negatively impacts endothelial function independently of the presence of additional CVRF through specific molecular mechanisms involving superoxide generation. While PPARgamma activation remains effective, the improving effects of PPARalpha agonists on endothelial responses disappear in aged human vessels. PMID- 22776134 TI - Graphical and demographic synopsis of the captive cohort method for estimating population age structure in the wild. AB - The purpose of this paper is to complement the literature concerned with the captive cohort method for estimating age structure including (1) graphic techniques to visualize and thus better understand the underlying life table identity in which the age structure of a stationary population equals the time-to death distribution of the individuals within it; (2) re-derive the basic model for estimating age structure in non-stationary population in demographic rather than statistical notation; and (3) describe a simplified method for estimating changes in the mean age of a wild population. PMID- 22776136 TI - Identification and characterization of an adenine to guanine transition within intron 10 of the factor VIII gene as a causative mutation in a patient with mild haemophilia A. AB - Haemophilia A is caused by various genetic mutations in the factor VIII gene (F8). However, after conventional analysis, no candidate mutation could be identified in the F8 of about 2% of haemophilia A patients. The F8 of a patient with mild congenital haemophilia A, in whom no candidate mutation was found in the exons or their flanking regions, was analysed in detail to identify the patient's aetiological genetic abnormality. We also characterized anti-FVIII antibody (inhibitor) development in this patient. Genomic DNA analysis revealed an adenine to guanine transition deep inside intron 10 (c.1478 + 325A>G) of F8 as a causative mutation. Analysis of the transcripts demonstrated that the majority of the patient's transcript was abnormal, with 226 bp of the intronic sequence inserted between exon 10 and 11. However, the analysis also indicated the existence of a small amount of normal transcript. Semi-quantification of ectopic F8 mRNA showed that about one-tenth of the normal mRNA level was present in the patient. After the use of a recombinant FVIII concentrate, the presence of an inhibitor was confirmed. The inhibitor was characterized as oligoclonal immunoglobulin IgG4 directed against both the A2 domain and light chain of the FVIII molecule with type I reaction kinetics of inhibition of FVIII activity. When no mutations are found by conventional analysis, deep intronic nucleotide substitutions may be responsible for mild haemophilia. The inhibitor development mechanism of the patient producing some normal FVIII was thought to be of interest. PMID- 22776135 TI - Lack of spontaneous venous pulsation: possible risk indicator in normal tension glaucoma? AB - PURPOSE: Recently, the absence of spontaneous venous pulsation (SVP) has been suggested as a vascular risk factor for primary open-angle glaucoma (POAG). As the mechanism behind this phenomenon is still unknown, the authors have studied this vascular component using colour Doppler imaging (CDI). METHODS: A total of 236 patients were divided into three diagnostic groups: healthy controls (81), POAG (86) and normal tension glaucoma (NTG; 69). All subjects were submitted to CDI studies of the retrobulbar circulation, intraocular pressure measurements and assessment of SVP existence. Mann-Whitney, chi-square contingency tables and Spearman correlations were used to explore differences and correlations between variables in the diagnostic groups. RESULTS: Eighty-two percent of healthy controls had SVP (66/81), while a smaller numbers were registered in both glaucoma groups: POAG - 50% (43/86); NTG - 51% (35/69). In NTG patients, but not in POAG patients, the prevalence of the SVP phenomenon decreases with increased glaucoma damage (p = 0.04; p = 0.55, respectively). Overall glaucoma patients from both groups had lower central retinal vein (CRV) velocities than the healthy controls (p < 0.05). NTG patients with SVP had less severe visual field defects (mean defect -6.92 versus -11.1, p < 0.05), higher [correction added after online publication 21 September 2012; the word 'higher' has been inserted to replace the word 'lower'] peak systolic and mean flow velocities in the central retinal artery (p < 0.01; p < 0.05, respectively) as well as higher [correction added after online publication 21 September 2012; the word higher has been inserted to replace the word lower] maximal velocities and RI of the CRV (p < 0.02; p < 0.05, respectively). CONCLUSIONS: Glaucoma patients have a decrease in CRV velocities. SVP is less prevalent in glaucoma patients than in healthy individuals. This phenomenon apparently reflects different hemodynamic patterns in the central retinal vessels. This variable may be of particular importance in NTG patients, where it may be associated with more advanced functional damage. PMID- 22776137 TI - Ankle joint mobilization decreases hypersensitivity by activation of peripheral opioid receptors in a mouse model of postoperative pain. AB - OBJECTIVE: Investigate whether ankle joint mobilization (AJM) decreases hypersensitivity in the mouse plantar incision (PI) model of postoperative pain as well as to analyze the possible mechanisms involved in this effect. DESIGN: Experiment 1: PI male Swiss mice (25-35 g, N = eight animals per group) were subjected to five sessions of AJM, each lasting either 9 or 3 minutes. AJM movement was applied at a grade III as defined by Maitland. Paw withdrawal frequency to mechanical stimuli was assessed before realization of PI and before and after daily AJM sessions. Mechanical hypersensitivity was also assessed following systemic (intraperitoneal [i.p.]) and local (intraplantar) injection of naloxone (a nonselective opioid receptor antagonist; 1 mg/kg, i.p.; 5 ug/paw, respectively, experiment 2); and systemic injection of fucoidin (100 ug/mouse, i.p., an inhibitor of leukocyte rolling, experiment 3) in different groups of mice. RESULTS: Nine but not 3 minutes of AJM reduced mechanical hypersensitivity caused by PI, an effect that was prevented by systemic and local administrations of naloxone but not by fucoidin. CONCLUSIONS: Our results indicate that joint mobilization reduces postoperative pain by activation of the peripheral opioid pathway. However, antihypersensitivity induced by AJM is apparently not limited by the number of opioid-containing leukocytes but by opioid receptors availability in sensory neurons. A better understanding of the peripheral mechanisms of AJM could stimulate therapists to integrate joint mobilization with strategies also known to influence endogenous pain control, such as exercise, acupuncture, and transcutaneous electrical nerve stimulation to potentiate endogenous analgesia. PMID- 22776138 TI - Impact of vitamin D supplementation on markers of bone mineral metabolism in term infants. AB - 25-Hydroxyvitamin D (25OHD) may influence bone turnover. We compared the dynamics of bone markers in 30 infants on vitamin D supplementation (?550 IU/day) with different degrees of hypovitaminosis D (25OHD <11 ng/ml - deficiency vs. >= 11 <20 ng/ml - insufficiency). Baseline and follow-up (after 10 weeks), 25OHD, 1,25 dihydroxyvitamin D (1,25(OH)(2)D), alkaline phosphatase (ALP), PTH, osteocalcin (OC), N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX), and amino-terminal propeptide of C-type natriuretic peptide (NT-proCNP) were measured. None of the newborns had craniotabes, hypocalcemia or hyperparathyroidism. The median (Q1;Q3) 25OHD increased from a baseline of 8.45 (7;11.9) ng/ml to 54.6 (34.7;67.3) ng/ml (p<0.001). The baseline 25OHD negatively correlated with total increment of 25OHD (r=-0.54; p=0.002). There were changes in ALP (241 vs. 331 IU; p<0.001), 1,25(OH)(2)D (48 vs. 95.5 pg/ml, p<0.001), OC (88.8 vs. 159.1 ng/ml, p<0.001), PINP (3886 vs. 2409 ng/ml; p<0.001), CTX (1.6 vs. 1.1 ng/ml; p<0.001), and NT-proCNP (75.1 vs. 35.1 pmol/l; p<0.001). Vitamin D deficient infants at baseline, compared to the insufficient group, revealed significantly higher percentage changes for 25OHD (745% vs. 167%, p<0.0001), OC (113% vs. 40%, p<0.05) and 1,25(OH)(2)D (95% vs. 58%, p<0.05). CONCLUSIONS: Vitamin D supplements had little to no impact on markers of bone turnover in term infants in the first few months of life, with the exception of osteocalcin. Ten weeks of cholecalciferol supplementation at a dose of 550 IU/day led to a marked increase of 25OHD concentration. The magnitude of 25OHD increment was inversely related to vitamin D status at baseline. Irrespective of the severity of vitamin D deficiency, a secondary hyperparathyroidism with elevated iPTH, ALP, phosphaturia or hypophosphatemia was not observed in the studied neonates. PMID- 22776139 TI - IL-4 inhibits TNF-alpha-mediated osteoclast formation by inhibition of RANKL expression in TNF-alpha-activated stromal cells and direct inhibition of TNF alpha-activated osteoclast precursors via a T-cell-independent mechanism in vivo. AB - It has been reported that osteoclastogenesis is induced by tumor necrosis factor (TNF)-alpha. Interleukin (IL)-4 is the most important cytokine involved in humoral immunity. However, no studies have investigated the effect of IL-4 on TNF alpha-mediated osteoclast formation in vivo. In this study, we investigated the effect of IL-4 on TNF-alpha-mediated osteoclast formation in vivo. TNF-alpha was administered with and without IL-4 into the supracalvariae of mice. The number of osteoclasts and the levels of mRNA for cathepsin K and tartrate-resistant acid phosphate, both osteoclast markers, in mice administered TNF-alpha and IL-4 were lower than those in mice administered TNF-alpha alone. The level of tartrate resistant acid phosphatase form 5b (TRACP5b) as a marker of bone resorption in mice administered both TNF-alpha and IL-4 was also lower. We showed that IL-4 inhibited TNF-alpha-mediated osteoclast formation in osteoclast precursors in vitro. Expression of receptor activator of NF-kappaB ligand (RANKL) in TNF-alpha activated stromal cells was also inhibited. Furthermore, we investigated whether IL-4 had effects on both stromal cells and osteoclast precursors in TNF-alpha mediated osteoclast formation in vivo. Using mice whose stromal cells and osteoclast precursors were chimeric for the presence of TNF receptors, IL-4 inhibited TNF-alpha-mediated osteoclast formation in the presence of TNF-alpha responsive stromal cells, and TNF-alpha-responsive osteoclast precursors in vivo. IL-4 also inhibited TNF-alpha-induced RANKL expression in the presence of TNF alpha-responsive stromal cells in vivo. This event is dependent on p38 inhibition in vitro. Additionally, IL-4 inhibited TNF-alpha-mediated osteoclast formation in T cell-depleted mice. In summary, we conclude that IL-4 inhibited TNF-alpha mediated osteoclast formation by inhibiting expression of RANKL in TNF-alpha activated stromal cells, and directly inhibited TNF-alpha-activated osteoclast precursors in vivo via a T cell-independent mechanism. PMID- 22776140 TI - Estimation of dynamic flux profiles from metabolic time series data. AB - BACKGROUND: Advances in modern high-throughput techniques of molecular biology have enabled top-down approaches for the estimation of parameter values in metabolic systems, based on time series data. Special among them is the recent method of dynamic flux estimation (DFE), which uses such data not only for parameter estimation but also for the identification of functional forms of the processes governing a metabolic system. DFE furthermore provides diagnostic tools for the evaluation of model validity and of the quality of a model fit beyond residual errors. Unfortunately, DFE works only when the data are more or less complete and the system contains as many independent fluxes as metabolites. These drawbacks may be ameliorated with other types of estimation and information. However, such supplementations incur their own limitations. In particular, assumptions must be made regarding the functional forms of some processes and detailed kinetic information must be available, in addition to the time series data. RESULTS: The authors propose here a systematic approach that supplements DFE and overcomes some of its shortcomings. Like DFE, the approach is model-free and requires only minimal assumptions. If sufficient time series data are available, the approach allows the determination of a subset of fluxes that enables the subsequent applicability of DFE to the rest of the flux system. The authors demonstrate the procedure with three artificial pathway systems exhibiting distinct characteristics and with actual data of the trehalose pathway in Saccharomyces cerevisiae. CONCLUSIONS: The results demonstrate that the proposed method successfully complements DFE under various situations and without a priori assumptions regarding the model representation. The proposed method also permits an examination of whether at all, to what degree, or within what range the available time series data can be validly represented in a particular functional format of a flux within a pathway system. Based on these results, further experiments may be designed to generate data points that genuinely add new information to the structure identification and parameter estimation tasks at hand. PMID- 22776141 TI - Breast cancer metastatic to the pituitary gland: a case report. AB - BACKGROUND: Metastases to the pituitary gland are rare events, and usually indicate widespread malignant disease. The lung and the breast are the most common sites of primary tumors that metastasize to the pituitary gland.Metastases are more frequent in older patients and the most common symptoms at presentation are diabetes insipidus and visual alterations. CASE PRESENTATION: 72-year-old white woman was treated for a breast carcinoma with right superoexternal quadrantectomy, radiotherapy, and hormone therapy. Twelve years later, the patient presented with bone pain, bilateral progressive visual decline, and onset of hypopituitarism. A diagnosis of secondary bone involvement and pituitary metastasis was made. CONCLUSION: This was an unusual disease course, and stresses the importance of intensive follow-up in patients with breast cancer even many years after the initial diagnosis This case emphasizes that diagnosis can be difficult and controversial when relapse occurs at uncommon sites. PMID- 22776142 TI - Safety and short-term effectiveness of EEA stapler vs PPH stapler in the treatment of degree III haemorrhoids: prospective randomized controlled trial. AB - AIM: Stapled haemorrhoidopexy has gained wide acceptance due to less postoperative pain although postoperative bleeding and prolapse recurrence are among the major drawbacks of this technique compared with the standard Milligan Morgan hemorrhoidectomy. The aim was to investigate a new stapler device designed to overcome these side effects. METHOD: In all, 135 patients (71 men, mean age 42 years) with degree III haemorrhoids were randomly allotted to stapled haemorrhoidopexy with PPH(r) staplers (Ethicon EndoSurgery) (63 patients) or with an EEA(r) stapler (Covidien) (72 patients) in four referral colorectal centres. The number of haemostatic overstitches apposed on the stapled suture, the area of the resected mucosa (in square centimetres) and any postoperative bleeding within 30 days were recorded. RESULTS: The mean area of the resected mucosa was significantly wider in EEA than PPH patients (35.75 +/- 17.51 vs 28.05 +/- 10.23 cm(2), P = 0.002). The median number of haemostatic stitches apposed in the EEA group was significantly lower than in the PPH groups (median value 1, vs 3, interquartile range 0-2, vs 2-5, P < 0.0001). Intraoperative haemostasis was better in the EEA group compared with the PPH01 and PPH03 groups. Postoperative bleeding occurred only in two PPH patients. CONCLUSION: Data suggest that the EEA stapler has better haemostatic properties than the PPH stapler and allows resection of a larger area of mucosal prolapse with potential benefits over the recurrence rate of haemorrhoid prolapse. PMID- 22776143 TI - Stem cell therapy for the spinal cord. AB - Injury and disease of the spinal cord are generally met with a poor prognosis. This poor prognosis is due not only to the characteristics of the diseases but also to our poor ability to deliver therapeutics to the spinal cord. The spinal cord is extremely sensitive to direct manipulation, and delivery of therapeutics has proven a challenge for both scientists and physicians. Recent advances in stem cell technologies have opened up a new avenue for the treatment of spinal cord disease and injury. Stem cells have proven beneficial in rodent models of spinal cord disease and injury. In these animal models, stem cells have been shown to produce their effect by the dual action of cell replacement and the trophic support of the factors secreted by these cells. In this review we look at the main clinical trials involving stem cell transplant into the spinal cord, focusing on motor neuron diseases and spinal cord injury. We will also discuss the major hurdles in optimizing stem cell delivery methods into the spinal cord. We shall examine current techniques such as functional magnetic resonance imaging guidance and cell labeling and will look at the current research striving to improve these techniques. With all caveats and future research taken into account, this is a very exciting time for stem cell transplant into the spinal cord. We are only beginning to realize the huge potential of stem cells in a central nervous system setting to provide cell replacement and trophic support. Many more trials will need to be undertaken before we can fully exploit the attributes of stem cells. PMID- 22776145 TI - Treatment choices for managing hyperglycaemia in patients with type 2 diabetes and moderate to severe renal disease. PMID- 22776144 TI - Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions. AB - INTRODUCTION: Lobular carcinoma in situ (LCIS) has been accepted as a marker of risk for the development of invasive breast cancer, yet modern models of breast carcinogenesis include LCIS as a precursor of low-grade carcinomas. We provide evidence favoring a clonal origin for LCIS and synchronous estrogen receptor positive malignant lesions of the ductal and lobular phenotype. METHODS: Patients with prior LCIS undergoing mastectomy were identified preoperatively from 2003 to 2008. Specimens were widely sampled, and frozen blocks were screened for LCIS and co-existing malignant lesions, and were subject to microdissection. Samples from 65 patients were hybridized to the Affymetrix SNP 6.0 array platform. Cases with both an LCIS sample and an associated ductal carcinoma in situ (DCIS) or invasive tumor sample were evaluated for patterns of somatic copy number changes to assess evidence of clonal relatedness. RESULTS: LCIS was identified in 44 of the cases, and among these a DCIS and/or invasive lesion was also identified in 21 cases. A total of 17 tumor pairs had adequate DNA/array data for analysis, including nine pairs of LCIS/invasive lobular cancer, four pairs of LCIS/DCIS, and four pairs of LCIS/invasive ductal cancer. Overall, seven pairs (41%) were judged to be clonally related; in five (29%) evidence suggested clonality but was equivocal, and five (29%) were considered independent. Clonal pairs were observed with all matched lesion types and low and high histological grades. We also show anecdotal evidence of clonality between a patient-matched triplet of LCIS, DCIS, and invasive ductal cancer. CONCLUSION: Our results support the role of LCIS as a precursor in the development of both high-grade and low-grade ductal and lobular cancers. PMID- 22776146 TI - The VINCat Program: quality and safety improvements in Catalonia. Editorial. PMID- 22776147 TI - The development and successful implementation of the VINCat Program. AB - In 2006 the VINCat Program was established in order to develop and support a standardized surveillance system of hospital-acquired infections (HAI). All acute care hospitals included in the public health system network of Catalonia (Spain) were invited to participate. The aim was to provide risk-adjusted, procedure specific rates for most relevant infections. Data are collected by the local multidisciplinary infection control teams and transmitted electronically to the Coordinating Centre, which acts as the core of a network of infection control committees and has the support of a Technical Advisory Committee. The program website provides updated information on program activities, training workshops, aggregated data on past infection rates and access to databases, manuals and protocols. During the period 2007-2011, 64 hospitals have joined the program: 9 tertiary, 16 district and 39 small hospitals, providing records on 4.044 episodes of catheter-related blood stream infections, 14.389 elective colorectal surgical interventions, 14.214 hip and 29.599 knee arthroplasties, among the most significant indicators. Nowadays, it appears that VINCat has been successfully implemented and is well established as the official HAI surveillance program in Catalonia. Determinants for success have been: the maintenance of a close contact between the hospitals and the coordinating center, the timely and regular data feedback to institutions, the program's contribution towards reducing HAIs, the ongoing efforts to improve performance and, a key factor, the perception among the infection control professionals of the value added by the program to their daily work in different ways. Adequate funding, commitment of infection control teams and the generous collaboration of experts from different specialties are essential for maintaining the success of the VINCat Program. PMID- 22776148 TI - Prevalence of nosocomial infections in acute care hospitals in Catalonia (VINCat Program). AB - The first objective of the Catalonian Nosocomial Infection Surveillance Program (VINCat) is to monitor the prevalence (%) of patients with nosocomial infections (NI), patients undergoing urinary catheterization with closed circuit drainage (%) and patients undergoing antibiotic treatment (%). We present the results for the period 2008-2010. Comprehensive and point annual prevalence surveys were conducted that included conventionally hospitalized patients in acute care hospitals belonging to the VINCat Program. The number of participating hospitals was 46 (2008), 48 (2009) and 61 (2010), most belonging to the Network of Public Use Hospitals of Servei Catala de la Salut. The results are presented globally and by hospital size (<200 beds, 200-500 beds, >500 beds). The prevalence of patients with active NI acquired during the current or the previous hospitalization (global NI/P%) was 7.6 (2008), 6.2 (2009) and 6.3 (2010). The prevalence of patients with active NI acquired during the current (actual NI/P%) was 6.2 (2008), 4.7 (2009) and 4.6 (2010).The results by hospital size shows that the variation occurred mainly in <200 beds hospitals. The proportion of closed circuit urinary catheterization use was 90.2%. The use of antibiotics varied between 34.6% and 37.6%, with no differences due to hospital size. The global prevalence of NI provides information on the burden of NI at the institutional and regional level. Between 17.3% and 26.9% of patients with NI at the time of the study had acquired it in a previous hospitalization at the same institution. PMID- 22776149 TI - Laboratory-based surveillance of hospital-acquired catheter-related bloodstream infections in Catalonia. Results of the VINCat Program (2007-2010). AB - The VINCat Program is an institutional surveillance program for hospital-acquired infections developed in the healthcare institutions of Catalonia, Spain. The program includes the monitoring of various components of hospital-acquired infection, among which is catheter-related bloodstream infection (CRBSI). The aim of this study was to describe the frequency of CRBSI in hospitals participating in the VINCat Program over a period of 4 years (2007-2010). The monitoring of the CRBSI component is carried out continuously in all inpatient units by performing a daily assessment of all blood culture results issued by the Microbiology Laboratories. Precise definitions are used for CRBSI, and adjusted rates are expressed per 1,000 days of hospitalization, hospital size and type of catheter. The rates of CRBSI in catheters used for parenteral nutrition are adjusted and expressed per 1,000 days of device use. The aggregate data of the total period are shown in percentiles (10%, 25%, 50% or median, 75%, and 90%). From 2007 to 2010, a total of 2977 episodes of CRBSI were reported in 40 hospitals participating in the VINCat Program. The cumulative incidence of CRBSI has been 0.26 episodes per 1,000 days of hospitalization (CI95% 0.2 to 0.3). The overall incidence varied depending on hospital size: 0.36 0/00 for hospitals in Group I (>500 beds), 0.17 0/00 for Group II (200-500 beds), and 0.09 0/00 for Group III (<200 beds). 76% of the episodes were associated with central venous catheters (CVC), 19% of the episodes with peripheral venous catheters (PVC), and the remaining 5% with peripherally inserted CVCs (PICC). The most common organisms causing CRBSI were staphylococci, the group Klebsiella, Serratia and Enterobacter, Candida spp., and Pseudomonas aeruginosa. There are important differences in the etiology of CRBSI in relation to these variables. During the reporting period, a significant reduction (38.1%, CI95%, 29.0-46.0%) of CRBSI rates have been observed in Group I hospitals. CRBSI surveillance is an important element of the VINCat Program, offering to us the possibility of establishing standard values for this component and implementing intervention strategies for its reduction. PMID- 22776150 TI - Surveillance of surgical site infections in elective colorectal surgery. Results of the VINCat Program (2007-2010). AB - The VINCat Program is a standardized surveillance program of healthcare infections in Catalonia, Spain. This program includes monitoring of surgical site infections (SSI) of elective colorectal surgery. The aim of this study was to define SSI rates in colorectal surgery among VINCat hospitals over a period of 4 years. We included consecutive elective colorectal interventions performed in VINCat hospitals from 2007 to 2010. Follow-up visits were performed 30 days after surgery. Prospective monitoring of SSI in colorectal surgery was performed according to standardized VINCat methodology. SSI was defined according to the Centers for Disease Control (CDC) and surgical risk factors according to the National Healthcare Safety Network (NHSN) classification. From 2007 to 2010, 49 centers performed 10,104 surgical procedures. The cumulative incidence of SSI was 20.8% (95% CI: 20.03-21.63). The annual cumulative SSI incidence rate did not vary significantly over the study period; however, there were significant differences among hospital infection rates. The relative frequency of organ-space infection increased from 25% in 2007 to 40% in 2010 (p<0.001). Laparoscopic surgery also increased (28% in 2007 to 42% in 2010, p<0.001). However, no changes were observed in mean surgery duration, ASA score and degree of surgical contamination. The VINCat Program incorporated a large number of Catalan hospitals that participated in standardized monitoring of colorectal surgery. The cumulative incidence rate of SSI for colorectal surgery was 20.8%, although there were large variations between hospitals. PMID- 22776151 TI - Epidemiology of surgical site infections after total hip and knee joint replacement during 2007-2009: a report from the VINCat Program. AB - The VINCat Program is a system for epidemiological surveillance of healthcare related infections in which the majority of Catalan hospitals participate. It has a specific module for surgical site infections (SSI) surveillance. Primary hip and knee arthroplasties are basic indicators of the program due to their high frequency and the important morbidity of SSI of these sites. Results are presented for surgical site infection (SSI) surveillance of primary hip and knee arthroplasties for the first three years of the VINCat Program. The program requires SSI surveillance to be performed in a standardized, prospective and continuous manner by an infection control team from the centers. With primary arthroplasties, as with all procedures involving implants, the surveillance is maintained for 1 year after the intervention. The VINCat Program uses the SSI definitions of the Centers for Disease Control (CDC) and patients are stratified by surgical risk, following the classification of the National Healthcare Safety Network (NHSN). During the period 2007-2009, 51 Catalan hospitals participated in the SSI surveillance of prosthetic orthopedic surgery. The overall SSI rate in the interventions for total primary hip prosthesis (7,804 procedures) was 3.0% (IC 95%: 2.6-3.4) and for total primary knee prosthesis (16,781 procedures) was 3.3% (IC95%: 3.0-3.6). During the period 2007-2009, the overall SSI rates for total primary hip and knee arthroplasty were higher than those published by some surveillance systems in our environment. There were significant differences in the infection rates by procedure and in those adjusted by risk among the different hospitals. PMID- 22776152 TI - Device-associated infection rates in Adult Intensive Care Units in Catalonia: VINCat Program findings. AB - Hospital-acquired infections are a leading cause of morbidity and mortality, especially in the intensive care unit (ICU). Surveillance of device-associated infections plays a major role in infection control programs. In 2006, the Surveillance Program of Nosocomial Infections in Catalonia (VINCat Program) was started, with the major aim of reducing infection rates through a process of active monitoring. The study period comprised calendar years 2008 (with 21 ICUs participating), 2009 (with 21 ICUs participating), and 2010 (with 28 ICUs participating). Each participating hospital was required to have an infection control team made up of at least one physician, an infection surveillance nurse, and a microbiology laboratory. Hospitals were classified into three groups according to their size. Central venous catheter-associated bloodstream infection (CVC-BSI) and ventilator-associated pneumonia (VAP) were chosen as the device associated infections to analyze. Incidence rates of device-associated infections were calculated by dividing the total number of device-associated infection (VAP or CVC-BSI) days by the total number of days use for the relevant device. Mechanical ventilation use ranged from 0.10 to 0.85 days (overall, 0.35), and central venous catheter use ranged from 0.18 to 0.98 days (overall, 0.65). Incidence rates of VAP ranged from 7.2 +/- 3.7 to 10.7 +/- 9.6 episodes of VAP/1000 ventilator days. Incidence rates of CVC-BSl ranged from 1.9 +/- 1.6 to 2.7 +/- 2.0 episodes of CVC-associated bloodstream infection/1000 central venous catheter days. The implementation of the VINCat Program allowed monitoring of nosocomial device-associated infections in ICUs in Catalonia and enabled corrective measures in ICUs with increased incidences of device-associated infections. PMID- 22776153 TI - Surveillance of methicillin-resistant Staphylococcus aureus (MRSA) in acute care hospitals. Results of the VINCat Program (2008-2010). AB - Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of healthcare-related infection. Surveillance and prevention of MRSA is a priority in infection control programs. The aim of this study was to describe rates and trends of MRSA colonization or infection in 40 hospitals participating in the VINCat Program from 2008 to 2010. The study included all patients treated in acute care areas of participating hospitals. Hospitals were stratified into 3 groups based on size. The following annual indicators were reported: Methicillin resistance rate, incidence density of new cases of MRSA and incidence density of MRSA bacteremia. Between 2008 and 2010, the yearly mean rate of resistance to methicillin remained stable for the study period (24%-25%), while the mean incidence of new cases of MRSA decreased from 0.65 to 0.54 cases per 1000 patient days (p=NS) and the mean incidence of MRSA bacteremia decreased from 0.06 to 0.05 cases per 1,000 patient-days (p=NS). The implementation of a MRSA surveillance system in hospitals that participated in the VINCat Program provides information on the situation of each institution and facilitated interhospital comparisons in order to establish appropriate preventive measures. PMID- 22776154 TI - Antibiotic consumption at 46 VINCat hospitals from 2007 to 2009, stratified by hospital size and clinical services. AB - The aim of the study was to assess the evolution of antibiotic consumption in acute care hospitals in Catalonia (population 7.5 million), according to hospital size and department, during the period 2007-2009. The methodology used for monitoring antibiotic consumption was the ATC/DDD system, and the unit of measurement was DDD/100 occupied bed-days (DDD/100 OBD). Hospitals were stratified according to size: I) large university hospitals (with more than 500 beds); II) medium-sized hospitals (between 200 and 500 beds); and III) small hospitals (fewer than 200 beds). The consumption was also analyzed and stratified according to department: medical, surgical and intensive care unit (ICU). Specific training in data management on antibiotic consumption was given to all participant hospitals before the implementation of the program. The mean antibiotic (J01) consumption, calculated in DDD/100 OBD, increased although without statistical significance (p=0.640): 74.68 (2007), 75.13 (2008) and 78.04 (2009). The values of the medians expressed in DDD/100 OBD in group I were 83.27 (in 2007), 82.16 (2008) and 86.93 (2009), in group II 72.60 (2007), 70.78 (2008) and 75.17 (2009) and in group III 65.66 (2007), 69.32 (2008) and 72.39 (2009). Antibiotic consumption was higher in large hospitals than in medium-sized or small hospitals. Catalan hospitals recorded an increase of 4.49% from 2007 to 2009, especially due to the rising use of carbapenems, cephalosporins, monobactams and the other antibiotic groups. PMID- 22776155 TI - Sonoelastographic evaluation of medial gastrocnemius muscles intrinsic stiffness after rehabilitation therapy with botulinum toxin a injection in spastic cerebral palsy. AB - OBJECTIVE: To investigate intrinsic stiffness changes using real-time sonoelastography (RTS) in the medial gastrocnemius muscle (GCM) after rehabilitation therapy with botulinum toxin type A (BTA) injection in spastic cerebral palsy (CP). DESIGN: Prospective study using ultrasonography and RTS. SETTING: An inpatient rehabilitation clinic. PARTICIPANTS: Children (N=17) with spastic CP (mean age, 57+/-22y, age range, 26-110mo). INTERVENTION: Rehabilitation therapy and intramuscular injection of BTA in both medial and lateral GCMs. MAIN OUTCOME MEASURES: RTS was obtained on the medial GCM, and the elastic pattern of the medial GCM was graded from RTS 1 (purple to green: soft) to RTS 4 (red: stiff) on the basis of color-scaled RTS. RTS score, color histogram, Modified Ashworth Scale (MAS) score of the ankle plantar flexor muscles, and Gross Motor Function Measure (GMFM) score were obtained before intervention and 4 weeks after intervention. The correlations among RTS score, GMFM, and MAS score were determined. Intrarater reliability was also evaluated. RESULTS: Before and at 4 weeks after intervention, the mean RTS score decreased from 3.4 to 1.5 (P<.05), median red pixel intensity decreased from 112.5 to 101.3 (P<.05), median blue pixel intensity increased from 82.6 to 90.4 (P<.05), mean MAS score of the ankle decreased from 2.7 to 1.3 (P<.05), and mean GMFM score increased from 54.55% to 62.32%. Significant correlations were observed between the RTS score and the MAS score. Intrarater reliability was high. CONCLUSIONS: Our results suggest that more information about the change of spastic muscle in CP after rehabilitation treatment with BTA may be gained by estimating muscle stiffness using RTS combined with clinical scale measurements. PMID- 22776156 TI - Enzymatic synthesis of valerena-4,7(11)-diene by a unique sesquiterpene synthase from the valerian plant (Valeriana officinalis). AB - Valerian (Valeriana officinalis) is a popular medicinal plant in North America and Europe. Its root extract is commonly used as a mild sedative and anxiolytic. Among dozens of chemical constituents (e.g. alkaloids, iridoids, flavonoids, and terpenoids) found in valerian root, valerena-4,7(11)-diene and valerenic acid (C15 sesquiterpenoid) have been suggested as the active ingredients responsible for the sedative effect. However, the biosynthesis of the valerena-4,7(11)-diene hydrocarbon skeleton in valerian remains unknown to date. To identify the responsible terpene synthase, next-generation sequencing (Roche 454 pyrosequencing) was used to generate ~ 1 million transcript reads from valerian root. From the assembled transcripts, two sesquiterpene synthases were identified (VoTPS1 and VoTPS2), both of which showed predominant expression patterns in root. Transgenic yeast expressing VoTPS1 and VoTPS2 produced germacrene C/germacrene D and valerena-4,7(11)-diene, respectively, as major terpene products. Purified VoTPS1 and VoTPS2 recombinant enzymes confirmed these activities in vitro, with competent kinetic properties (K(m) of ~ 10 MUm and k(cat) of 0.01 s(-1) for both enzymes). The structure of the valerena-4,7(11) diene produced from the yeast expressing VoTPS2 was further substantiated by (13) C-NMR and GC-MS in comparison with the synthetic standard. This study demonstrates an integrative approach involving next-generation sequencing and metabolically engineered microbes to expand our knowledge of terpenoid diversity in medicinal plants. PMID- 22776157 TI - Trends in socioeconomic inequalities in anthropometric status in a population undergoing the nutritional transition: data from 1982, 1993 and 2004 Pelotas birth cohort studies. AB - BACKGROUND: Socioeconomic inequalities in child nutrition may change rapidly over time, particularly in populations undergoing the nutrition transition. Yet, the few available studies are repeated cross-sectional surveys. By studying three prospective birth cohorts in the same city over a period of more than two decades, we describe secular trends in overweight and stunting at different ages, according to socioeconomic position. METHODS: Population-based birth cohort studies were launched in the city of Pelotas (Brazil) in 1982, 1993 and 2004, with follow-up visits at twelve, 24 and 48 months. Children were weighed and measured at every visit. Z-scores of length/height-for-age and body mass index for-age were calculated using the WHO Child Growth Standards. The slope and relative indices of inequality, based on family income quintiles, were estimated for each follow-up visit. RESULTS: Between the 1982 and 2004 cohorts, stunting among four-year-olds declined (from 10.9% to 3.6%), while overweight increased (from 7.6% to 12.3%). In every visit, stunting prevalence was inversely related to income. Both absolute and relative inequalities declined over time; among four year-olds stunting dropped from 26.0% in the 1982 cohort to 6.7% in the 2004 cohort in the poorest group, while in the richest group stunting prevalence dropped from 2.7% in 1982 to 1.1% in the 2004 cohort study. The secular trend towards increased overweight was evident for four-year-olds, in almost all socioeconomic groups, but not among one and two-year-olds. Among four-year old children, overweight prevalence increased in all income quintiles, by 130% in the middle-income group, 64% in the poorest and 41% in the richest group. CONCLUSIONS: The decline in stunting is remarkable, but the increase in overweight among four-year olds - particularly among the poorest and the middle income groups- requires concerted efforts to prevent the long term consequences of child overweight. PMID- 22776159 TI - The dopamine D1 but not D3 receptor plays a fundamental role in spatial working memory and BDNF expression in prefrontal cortex of mice. AB - Although dopamine within the prefrontal cortex has been implicated in working memory, how different dopamine receptor subtypes contribute to this process need to be further characterized. Previous studies have suggest the importance of dopamine receptors signaling in regulating the brain-derived neurotrophic factor (BDNF) function that is associated with synaptic plasticity underlying normal memory formation. Changes in BDNF expression through the dopamine receptors within the prefrontal cortex may accompany and mediate the spatial working memory. To test the possibility, dopamine D1 and D3 receptor mutant mice were tested in Morris water maze for spatial working memory. We found that trial dependent, matching-to-sample, learning of the platform location, an index of short-term spatial working memory in mice, was significantly impaired in D1 receptor knockout mice compared to wild-type mice, and regular performance of D3 receptor mutants was observed in the similar working memory task. BDNF protein was significantly decreased in prefrontal cortex, though not in hippocampus, of the D1 receptor knockout mice, whereas no changes were found in both prefrontal cortex and hippocampus of D3 receptor knockout mice. These data suggest that dopamine D1 but not D3 receptors are critical for prefrontal cortex BDNF expression which may be related to spatial working memory processes. PMID- 22776160 TI - Prenatal ethanol exposure impairs passive avoidance acquisition and enhances unconditioned freezing in rat offspring. AB - Previous studies have suggested that ethanol exposure during brain development affects responses to fear and anxiety after maturity. To clarify in detail the impaired behavior related to fear and anxiety seen in rat offspring prenatally exposed to ethanol, their behaviors were observed using an elevated T-maze (ETM) test, which allows assessment of passive avoidance acquisition and one-way escape separately, and an elevated open platform (EOP) test for the assessment of unconditioned freezing against innate fear. The ETM test revealed that acquisition of passive avoidance was significantly inhibited in prenatally ethanol-exposed rats, while their escape behavior was not altered. In the EOP test, the duration of the freezing behavior was significantly elongated in prenatally ethanol-exposed offspring. Thus, we concluded that prenatal ethanol exposure could impair acquisition of passive avoidance, while it could facilitate a response related to unconditioned fears in rat offspring. PMID- 22776158 TI - Tissue-specific differential induction of duplicated fatty acid-binding protein genes by the peroxisome proliferator, clofibrate, in zebrafish (Danio rerio). AB - BACKGROUND: Force, Lynch and Conery proposed the duplication-degeneration complementation (DDC) model in which partitioning of ancestral functions (subfunctionalization) and acquisition of novel functions (neofunctionalization) were the two primary mechanisms for the retention of duplicated genes. The DDC model was tested by analyzing the transcriptional induction of the duplicated fatty acid-binding protein (fabp) genes by clofibrate in zebrafish. Clofibrate is a specific ligand of the peroxisome proliferator-activated receptor (PPAR); it activates PPAR which then binds to a peroxisome proliferator response element (PPRE) to induce the transcriptional initiation of genes primarily involved in lipid homeostasis. Zebrafish was chosen as our model organism as it has many duplicated genes owing to a whole genome duplication (WGD) event that occurred ~230-400 million years ago in the teleost fish lineage. We assayed the steady state levels of fabp mRNA and heterogeneous nuclear RNA (hnRNA) transcripts in liver, intestine, muscle, brain and heart for four sets of duplicated fabp genes, fabp1a/fabp1b.1/fabp1b.2, fabp7a/fabp7b, fabp10a/fabp10b and fabp11a/fabp11b in zebrafish fed different concentrations of clofibrate. RESULT: Electron microscopy showed an increase in the number of peroxisomes and mitochondria in liver and heart, respectively, in zebrafish fed clofibrate. Clofibrate also increased the steady-state level of acox1 mRNA and hnRNA transcripts in different tissues, a gene with a functional PPRE. These results demonstrate that zebrafish is responsive to clofibrate, unlike some other fishes. The levels of fabp mRNA and hnRNA transcripts for the four sets of duplicated fabp genes was determined by reverse transcription, quantitative polymerase chain reaction (RT-qPCR). The level of hnRNA coded by a gene is an indirect estimate of the rate of transcriptional initiation of that gene. Clofibrate increased the steady-state level of fabp mRNAs and hnRNAs for both the duplicated copies of fabp1a/fabp1b.1, and fabp7a/fabp7b, but in different tissues. Clofibrate also increased the steady state level of fabp10a and fabp11a mRNAs and hnRNAs in liver, but not for fabp10b and fabp11b. CONCLUSION: Some duplicated fabp genes have, most likely, retained PPREs, but induction by clofibrate is over-ridden by an, as yet, unknown tissue specific mechanism(s). Regardless of the tissue-specific mechanism(s), transcriptional control of duplicated zebrafish fabp genes by clofibrate has markedly diverged since the WGD event. PMID- 22776161 TI - From plant biomass to bio-based chemicals: latest developments in xylan research. AB - For a hundred years or more, oil and natural gas has supplied fuel and other raw chemicals to support economic growth. In the last decades their shrinking reservoirs and the increasing cost of production has become obvious, leading researchers to look for alternative substitutes of all the chemical materials presently derived from oil and gas. This review is focused on xylan, the second most abundant plant polysaccharide on our planet. Some xylan-derived products have already found commercial applications (ethanol, xylitol, xylo oligosaccharides) while others could have a great future in a wide range of industries. The chemical and structural variations of xylans produced by different plants, and the concentration of xylan in various plant resources are summarized. This review discusses the latest research developments in extraction and purification methodologies, and chemical modification, as well as the analytical methods necessary for xylan related research. PMID- 22776162 TI - Norovirus outbreak of probable waterborne transmission with high attack rate in a Guatemalan resort. AB - BACKGROUND: In February 2009, a group of Guatemalan school children developed acute gastroenteritis (AGE) after participating in a school excursion. OBJECTIVES: We conducted a retrospective cohort investigation to characterize the outbreak and guide control measures. STUDY DESIGN: A case was defined as an illness with onset of diarrhea or vomiting during February 25-March 5, 2009. Participants were interviewed using a standardized questionnaire, and stool specimens were collected. We inspected the excursion site and tested water samples for total coliforms and Escherichia coli. RESULTS: We identified 119 excursion participants, of which 92 (77%) had been ill. Fifty-six (62%) patients sought care for their illness, and three (3%) were hospitalized. Eighteen (90%) of the 20 specimens from ill children tested positive for norovirus. Among these, 16 (89%) were of the genogroup I (GI.7) and two (11%) were genogroup II (GII.12 and GII.17). One (8%) of the 12 food handlers had norovirus (GI.7). Drinking water samples had 146 most probable numbers (MPN)/100ml of total coliforms and five MPN/100ml of E. coli. CONCLUSION: We describe the first laboratory-confirmed norovirus outbreak in Guatemala. The high illness attack rate, detection of multiple norovirus strains in sick persons, and presence of fecal contamination of drinking water indicate likely waterborne transmission. PMID- 22776163 TI - Evaluation of blood collection filter papers for HIV-1 DNA PCR. AB - BACKGROUND: The collection of dried blood spots (DBS) on Whatman 903 cards has facilitated for years the detection of HIV-1 in infants by DNA PCR as early as 4 6 weeks after birth in resource-limited settings (RLS), but alternate blood collection devices are proving to be necessary. OBJECTIVES: The qualitative detection of HIV-1 DNA by PCR from DBS prepared on three commercially available blood collection cards was evaluated at the Centers for Disease Control and Prevention (CDC) and in four laboratories in Africa. STUDY DESIGN: DBS were prepared on Ahlstrom grade 226, Munktell TFN and Whatman 903, and stored under a variety of conditions. DBS were stored at ambient temperature (RT), 37 degrees C with high humidity, and -20 degrees C for varying lengths of time. The presence of HIV-1 DNA was tested using Roche Amplicor HIV-1 DNA (v 1.5) weekly for 4 weeks and at weeks 8 and 12 (RT and 37 degrees C), at weeks 4, 8, and 18 (-20 degrees C) of storage. DBS specimens were also tested after international shipment at RT. In addition, after nearly 3 years storage at -20 degrees C, DBS were also evaluated independently using the COBAS Ampliprep/TaqMan HIV-1 Qual and Abbott RealTime HIV-1 Qualitative tests. RESULTS: HIV-1 DNA was detected equally well on the three blood collection cards regardless of storage conditions and PCR assay. CONCLUSIONS: Ahlstrom 226 and Munktell TFN papers were comparable to Whatman 903 for HIV-1 DNA detection and may be considered as optional blood collection devices in resource-limited countries. PMID- 22776164 TI - Human menstrual blood-derived mesenchymal cells as a cell source of rapid and efficient nuclear reprogramming. AB - Induced pluripotent stem cells (iPSCs) were originally generated by forced ectopic expression of four transcription factors genes-OCT4, KLF4, SOX2, and c MYC-in fibroblasts. However, the efficiency of iPSCs obtention is extremely low, and reprogramming takes about 20 days. We reasoned that adult cells showing basal expression of core embryonic stem (ES) cell regulator genes could be a better cell source for reprogramming. Menstrual blood-derived mesenchymal cells (MBMCs) are multipotent cells that show detectable levels of some of the core ES cells regulators. The aim of this study was to determine whether reprogramming efficiency could be increased by using MBMCs as a cell source to generate iPSCs. MBMCs were transduced with recombinant retroviruses expressing the coding regions of OCT4, SOX2, and KLF4 genes. Cells with high nucleus/cytoplasm ratio can be detected about 5 days of posttransduction, and colonies of typical ES-like cells begun to appear after 7 days. At day 15, colonies were picked up and expanded for characterization. Most of the clones were morphologically identical to ES cells and positive at the mRNA and protein levels for all pluripotency markers tested. The clones are capable of forming embryoid bodies and to differentiate in vitro into cells of the three germ cell layers. Our results show that the reprogramming was faster and with efficiency around 2-5%, even in the absence of ectopic expression of c-MYC. To date, this is the first study showing MBMCs as a cell source for nuclear reprogramming. PMID- 22776166 TI - Outcome of laparoscopic surgery for colon cancer in elderly patients. AB - INTRODUCTION: The aim of this study was to evaluate whether elderly patients with colorectal cancer benefit from laparoscopic colon surgery (LAC) in comparison to open colon surgery (OC). METHODS: Patients with colon cancer were divided into four groups; >75 years (CC(>75) ) [LAC(>75) (n=36), OC(>75) (n=15)] and <=75 years [LAC(<=75) (n=90), OC(<=75) (n=26)]. Differences in postoperative short term outcomes were analyzed among the age and procedure groups. RESULTS: Intraoperative blood loss was significantly less in the LAC(>75) group (68 +/- 168 ml) than in the OC(>75) group (118 +/- 130 ml, P=0.040). The C-reactive protein of patients in the OC(>75) group (5.4 +/- 2.2 mg/dl) tended to be less than that of the LAC(>75) group (6.1 +/- 2.8 mg/dl, P=0.080) on postoperative day 1. The time to the first passage of flatus was significantly shorter in the LAC(>75) group (2.0 +/- 0.7 days) than in the OC(>75) group (2.7 +/- 0.8 days, P=0.003). Postoperative hospital stays were also shorter in the LAC(>75) group (14.2 +/- 9.4 days) than in the OC(>75) group (18.0 +/- 8.3 days, P=0.038). No mortality was registered in the LAC(>75) group, while one patient in the OC(>75) group died during the postoperative course. The rate of postoperative morbidity was similar between the LAC(>75) and OC(>75) groups [13.9% (5/36) versus 20.0% (3/15), P=0.679]. CONCLUSION: LAC provides some advantages over OC in patients with colon cancer aged >75 years as well as in those aged <=75 years. LAC can be safely performed in very elderly patients with colon cancer. PMID- 22776167 TI - Novel procedure, SILSOID colectomy, is a bridge between conventional and single incisional laparoscopic colectomy. AB - INTRODUCTION: Laparoscopic colectomy (LC) is a widely accepted treatment for various diseases of the colon. Transumbilical single-incisional laparoscopic surgery (SILS) offers excellent cosmetic results compared with standard multi port laparoscopic surgery. We describe a new hybrid laparoscopic procedure, SILSOID colectomy, which combines conventional LC with SILS. METHODS: We performed SILSOID colectomy to treat four patients with colorectal disease. Three ports were inserted through the single transumbilical incision, and an additional port was inserted in the flank at a site that depended on the location of the lesion. Division and anastomosis of the colon were performed extracorporeally. RESULTS: SILSOID colectomy was carried out uneventfully in all four cases. The median operation time was 220 minutes (range, 179-320 min), and the median blood loss was negligible (range, negligible-285 mL), respectively. Although one patient experienced a postoperative wound infection, no other postoperative complications occurred. CONCLUSION: SILSOID colectomy is safe and feasible and it can be used as an alternative to conventional LC. We consider this procedure to be a bridge between conventional LC and more advanced laparoscopic procedures, such as SILS. PMID- 22776165 TI - Identification of multiple RIG-I-specific pathogen associated molecular patterns within the West Nile virus genome and antigenome. AB - The ability of viruses to control and/or evade the host antiviral response is critical to the establishment of a productive infection. One of the strategies utilized by West Nile virus (WNV) to circumvent the host response is to evade detection by the pathogen recognition receptor RIG-I early in infection. To begin elucidating the mechanisms by which WNV eludes detection, we undertook a systematic analysis of the WNV genome and antigenome to identify RIG-I-specific pathogen associated molecular patterns (PAMPs). Multiple segments of the WNV genome and anitigenome induced a RIG-I-specific antiviral response. However, incorporation of the stimulatory regions into larger RNAs substantially reduced their capacity to activate RIG-I. These results suggested that WNV evades the host response by sequestering RIG-I-specific PAMPs within the complete genome and antigenome at early times post-infection. Furthermore, activation of the RIG-I pathway may require the liberation of PAMPs by the cell's normal RNA processing pathways. PMID- 22776168 TI - Laparoscopy-assisted appendectomy through an umbilical port in children. AB - INTRODUCTION: We report surgical techniques for single-incision laparoscopy assisted surgery (SILAS) in the treatment of pediatric acute appendicitis. METHODS: We performed SILAS in 15 cases of acute appendicitis between January and September of 2009. SILAS is a surgical method that involves making the incision at the umbilicus, inserting a wound retractor XS, suspending the abdominal wall with a hook, and appendectomy with the same procedures as conventional appendectomy. RESULTS: SILAS appendectomy was performed in all 15 cases with the exception of one case where one 3-mm port was added. Compared to open appendectomy, blood loss was significantly lower and postoperative hospitalization time was shorter, although there was no significant decrease in operative time, or postoperative fasting time. No postoperative complications, such as wound infection, intestinal obstruction, intra-abdominal abscess, or bleeding, were encountered. CONCLUSION: SILAS was safely performed and is superior to open appendectomy with regard to cosmetic outcome. PMID- 22776169 TI - Laparoscopic adrenalectomy by general surgeons familiar with laparoscopic surgical skills: experiences of a single center. AB - INTRODUCTION: Laparoscopic adrenalectomy (LA) is still considered an advanced procedure requiring a high level of skills with potentially lethal pitfalls. We report our clinical outcomes of 50 cases of LA, and discuss whether a general surgeon is suitable to perform LA, and the effect of mentor-initiated training on improving outcomes. METHODS: Patients' age and sex, size of tumor, preoperative diagnosis, procedure details, intra- and postoperative complications, operation time, final histological diagnosis, and length of stay of 50 consecutive cases of LA were collected through a review of hospital charts. These cases were divided into two equal consecutive groups. The first 25 cases were named Group A, and the latter 25 cases were named Group B, and two groups were compared. RESULTS: Median operation time in Group B (110 min) was significantly shorter than that in Group A (125 min) (P=0.021). Mean postoperative hospital stay in Group B (7.0 +/- 2.8 days) was significantly shorter than that in Group A (10.9 +/- 8.8 days) (P=0.019). Only one case (Group B) of 50 LA (2%) required a conversion to open adrenalectomy because of failure to control bleeding during dissection. CONCLUSION: Under mentor-initiated training, general surgeons with experience of more than 50 cases of laparoscopic cholecystectomies can attain favorable clinical outcomes in LA. PMID- 22776170 TI - Vaginal cuff dehiscence after total laparoscopic hysterectomy: examination on 677 cases. AB - INTRODUCTION: Total laparoscopic hysterectomy has been reported as having a higher incidence of vaginal cuff dehiscence compared with the abdominal and/or vaginal hysterectomy. The cause of vaginal cuff dehiscence after total laparoscopic hysterectomy is not specified, but possible causes may be the use of thermal energy for vaginal incision, reduced suturing width due to magnification, low quality of laparoscopic suturing skills and early resumption of regular activities after surgery. METHODS: We performed 677 cases of total laparoscopic hysterectomy for benign diseases, such as fibroids or adenomyosis, from January 2007 to December 2008 in our institute. We experienced four cases (0.6%) of vaginal cuff dehiscence. We checked the operative parameters for these cases, such as whether the retroperitoneum was sutured or not and intrapelvic adhesion, as well as examined operative duration, blood loss, weight of removed organs, and body mass index. RESULTS: Sexual intercourse was the triggering event for three cases (96 days, 103 days and 47 days after total laparoscopic hysterectomy) and the other case occurred during defecation (18 days and no sexual intercourse after total laparoscopic hysterectomy). There were no significant differences in vaginal cuff dehiscence with or without retroperitoneum suture and intrapelvic adhesion. CONCLUSION: After these four cases of vaginal cuff dehiscence, we recognized the need to review these cases carefully in order to discover the cause and how to prevent this from occurring in other patients. We do not have the answers to prevent this complication at present, but reducing the power source and attempting different suturing techniques may be important steps. PMID- 22776171 TI - Revisional bariatric surgery for failed gastric banding in Asia: a review of choice of revisional procedure, surgical technique and postoperative complication rates. AB - INTRODUCTION: In Asia, long-term weight loss results of gastric banding have been unsatisfactory. Bands are associated with higher complication rates, which result in a high reoperation rate. The aim of this paper is to discuss the choice of revisional procedure, operative technique and evaluate the postoperative complication rates. METHODS: Between January 2007 and January 2010, we operated on 41 patients who were included retrospectively in this series. The most common reason for band removal was failure to lose adequate weight. Of those patients, 40 underwent band removal and conversion to a revisional bariatric surgery concomitantly; one patient's procedure was deferred to a later date. LSG was performed in 26 and LRYGB in 15. The highlights of the operative technique were meticulous dissection, complete removal of the pseudocapsule, choosing the right stapler cartridge, oversewing and inverting the entire staple line, and complete dissection of the left crus and pars flaccid. RESULT: The median duration of surgery was 85 min (range, 55-180 min). There was no conversion to open surgery. The median stay in the hospital was 4 d (range, 2-7 d). There were no leaks or any other major complications in the postoperative period. CONCLUSION: Concomitant revisional procedure after removal of gastric band is safe and feasible. The operative technique followed at our center has had an extremely low postoperative morbidity rate and a 0% leak rate. PMID- 22776172 TI - A case of Helicobacter pylori infection complicated with gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma, and idiopathic thrombocytopenic purpura successfully treated with laparoscopy-assisted total gastrectomy and splenectomy. AB - Helicobacter pylori infection plays a key role in the pathogenesis of H. pylori associated diseases, including gastroduodenal and non-gastroduodenal diseases. A 71-year-old man was evaluated for a positive fecal occult blood test by upper gastrointestinal endoscopy, which revealed H. pylori infection, two adenocarcinomas and two gastric mucosa-associated lymphoid tissue lymphomas. Hematological examination revealed low platelet-count, elevated platelet associated immunoglobulin G and anti-H. pylori immunoglobulin G antibodies. We diagnosed H. pylori infection complicated by simultaneous occurrence of gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma, and idiopathic thrombocytopenic purpura. These diseases were successfully treated with laparoscopy-assisted total gastrectomy and splenectomy, and there was no evidence of recurrence for about 2 years. This is the first reported case of H. pylori infection complicated by these three diseases and cured with laparoscopic surgery. PMID- 22776173 TI - Endoscopic removal of herniated nucleus pulposus migrated dorsally to the dural sac. AB - A herniated nucleus pulposus (HNP) migrated dorsally to the dural sac is a rare condition. Here, we present a case, in which the HNP was removed with minimally invasive spinal endoscopy. A 54-year-old man presented complaining of left leg pain and paresis. Neurologic findings and an MRI suggested an epidural tumor or a dorsally migrated HNP compressing the S1 nerve root and dural sac. With a spinal endoscope, careful laminotomy of caudal L5 and cranial S1 was made. En bloc flavectomy exposed a mass covered with a thin capsule. The mass was identified as a dorsally migrated HNP. After complete HNP fragment removal, the dural sac and S1 nerve root were decompressed. Immediately postoperative, the leg pain subsided and motor function normalized, although the patient complained of numbness at the S1 dermatome area. In summary, a large HNP that had migrated dorsally to the dural sac was successfully removed endoscopically. PMID- 22776174 TI - Remote access laparoscopic (REAL) surgery: a novel approach for single-port surgery without a visible scar. AB - INTRODUCTION: Single-port laparoscopic surgery usually uses the transumbilical approach. However, the transumbilical incision may be associated with a high frequency of wound-related complications, including trocar site hernia and infection. Therefore, we developed remote access laparoscopic (REAL) surgery, a new access technique for single-port surgery within the pubic hairline. This study reports on a technique developed at our institution and describes our preliminary results. MATERIALS AND SURGICAL TECHNIQUE: Ten patients with cholecystolithiasis underwent REAL surgery. A single 2.5-cm transverse incision was made medially within the pubic hairline area, and a SILS Port was inserted. A 5-mm flexible endoscope and an articulating grasper or a long laparoscopic grasper were used. Dissection of the gallbladder was achieved with laparoscopic ultrasonic shears just as in the conventional laparoscopic cholecystectomy. All procedures were successfully performed without conversion to conventional laparoscopic technique. There were no postoperative complications, and outpatient evaluation showed a clean scar within the pubic hair area in all patients. DISCUSSION: Our early experience shows that REAL surgery is feasible and safe. This novel access technique can preserve the native umbilicus and provides an invisible scar that is concealed within the pubic hair. PMID- 22776175 TI - Re: Bowel obstruction associated with endoscopic tattooing of the colon with India ink (Asian J Endosc Surg 3 (2010) 150-152). PMID- 22776176 TI - Histone deacetylase inhibitors promote mice corneal allograft survival through alteration of CD4+ effector T cells and induction of Foxp3+ regulatory T cells. AB - Trichostatin A (TSA) is classical Histone deacetylase inhibitors (HDACIs) II which is used in treatment of advanced cutaneous T-cells lymphoma. Our works focused on the roles of TSA on immuno-modulatory. We found that the TSA could induce resting Teff cells into apoptotic cell death and inhibit Teff cells proliferation in a dose-dependent manner. We also observed down-regulation effects of various costimulatory/adhesion molecules on Teff cells and up regulation of Foxp3 expression on CD4+ CD25+ T cells. Treatment with TSA could improve mice corneal allograft survival by promoting the proportions and allosuppressive function of CD4+ CD25+ regulatory T cells. Our findings suggest that the use of TSA allows the beneficial pharmacological effect on CD4+ CD25- T activation in vitro and enhancement of Foxp3+ Treg cells in vivo. PMID- 22776178 TI - Electrospun polystyrene-poly(styrene-co-maleic anhydride) nanofiber as a new aptasensor platform. AB - Here, we report the use of an aptamer-immobilized electrospun polystyrene poly(styrene-co-maleic anhydride) (PS-PSMA) nanofiber as a new aptasensor platform for protein detection. Two thrombin-binding aptamers (TBA29 and TBA15) were used as a model platform to facilitate efficient detection of thrombin in a sandwich manner. Thrombin concentration was measured by fluorescence microscopy and spectroscopy, in which aptamers were labeled with either fluorescein dye or quantum dots. The results indicated that thrombin was captured uniformly on the surface of the nanofiber. Using this sandwich-type biosensor, the minimum detectable concentration of thrombin was 10 pM, with a dynamic range of 0.1-50 nM, when quantum dots were used for labeling. In contrast, the limit of detection was 1 nM, with a dynamic range of 10-200 nM, when using fluorescein dye labeling. This aptamers-on-nanofiber-based biosensor showed 2500-fold higher sensitivity than a 96-microwell plate format, attributed mainly to the large surface area of the nanofibers. In addition, this novel platform also exhibited similar high sensitivity in the detection of exogenously added thrombin in diluted human serum. This aptamers-on-nanofiber system, which is competitive with other sensing platforms and clinically meaningful in terms of its detection limit, is expected to be useful for the detection of various other targets because of its ease of application and manipulation. PMID- 22776177 TI - DNAzyme-functionalized Pt nanoparticles/carbon nanotubes for amplified sandwich electrochemical DNA analysis. AB - A novel DNAzyme-functionalized Pt nanoparticles/carbon nanotubes (DNAzyme/Pt NPs/CNTs) bioconjugate was fabricated as trace tag for ultrasensitive sandwich DNA detection. The Pt NPs/CNTs were prepared via layer-by-layer (LBL) assembly of the Pt NPs and polyelectrolyte on the carboxylated CNTs, followed by the functionalization with the DNAzyme and reporter probe DNA through the platinum sulfur bonding. The subsequent sandwich-type DNA specific reaction would confine numerous DNAzyme/Pt NPs/CNTs bioconjugate onto the gold electrode surface for amplifying the signal. In the presence of 3,3',5,5' tetramethylbenzidine (TMB) which could be oxidized by the DNAzyme, electrochemical signals could be generated by chronoamperometry via the interrogation of reduction electrochemical signal of oxidized TMB. The constructed DNA sensor exhibited a wide linear response to target DNA ranging from 1.0 fM to 10 pM with the detection limit down to 0.6 fM and exhibited excellent selectivity against even a single base mismatch. In addition, this novel DNA sensor showed fairly good reproducibility, stability, and reusability. PMID- 22776179 TI - X-ray enabled detection and eradication of circulating tumor cells with nanoparticles. AB - The early detection and eradication of circulating tumor cells (CTCs) play an important role in cancer metastasis management. This paper describes a new nanoparticle-enabled technique for integrated enrichment, detection and killing of CTCs by using magnetic nanoparticles and bismuth nanoparticles, X-ray fluorescence spectrometry, and X-ray radiation. The nanoparticles are modified with tumor targeting agents and conjugated with tumor cells through folate receptors over-expressed on cancer cells. A permanent micro-magnet is used to collect CTCs suspended inside a flowing medium that contains phosphate buffered saline (PBS) or whole blood. The characteristic X-ray emissions from collected bismuth nanoparticles, upon excitation with collimated X-rays, are used to detect CTCs. Results show that the method is capable of selectively detecting CTCs at concentrations ranging from 100-100,000 cells/mL in the buffer solution, with a detection limit of ~ 100 CTCs/mL. Moreover, the dose of primary X-rays can be enhanced to kill the localized CTCs by radiation induced DNA damage, with minimal invasiveness, thus making in vivo personalized CTC management possible. PMID- 22776180 TI - Electrochemical immunoassay on expression of integrin beta1 on tumor cells and drug-resistant tumor cells. AB - An electrochemical indirect competitive immunoassay protocol as a promising cytosensing strategy was developed to detect integrin beta1 expression on human breast cancer MCF-7 cells and adriamycin-resistant human breast cancer MCF-7 (MCF 7/ADR) cells and quantify the cell number. Integrin alpha5beta1 was adsorbed on the gold-nanoparticle modified glassy carbon electrode to bind integrin beta1 monoclonal antibody (anti-CD29 mAb). A sandwich structure was then formed using nanocomposites which consisted of horseradish peroxidase (HRP) labeled anti antibody and gold nanoparticles. HRP bound on the electrode surface could cause an amperometric response of the hydroquinone-H(2)O(2) system. The assembly of the sandwich structure was inhibited by tumor cells to give decreased enzyme catalytic signals due to the capture of anti-CD29 mAb by integrin beta1 on cell membranes. Under optimal conditions the relative current change (S) was proportional to the cell concentration from 1.6 * 10(3) to 2.0 * 10(6) cells mL( 1) with a detection limit of 700 cells mL(-1). Integrin beta1 expression in MCF 7/ADR cells was found to be significantly higher than that in MCF-7 cells, indicating the increased adhesion ability of MCF-7/ADR cells. PMID- 22776181 TI - Electrochemical based detection of microRNA, mir21 in breast cancer cells. AB - In this work, a novel electrochemical microRNA (miRNA) detection method based on enzyme amplified biosensing of mir21 from cell lysate of total RNA was demonstrated. The proposed enzymatic detection method was detailed and compared with the conventional guanine oxidation based assay in terms of detection limit and specificity. For the detection of mir21, capture probes and/or cell lysates were covalently attached onto the pencil graphite electrode (PGE) by coupling agents of N-(dimethylamino)propyl-N'-ethylcarbodiimide hydrochloride (EDC) and N hydroxysulfosuccinimide (NHS). Having immobilized the capture probe onto the surface of PGE, hybridization was achieved with a biotinylated (from its 3' end) complementary target. Extravidin labeled alkaline phosphatase (Ex-Ap) binds to the biotinylated target due to the interaction between biotin-avidin and the enzyme converts electro-inactive alpha naphtyl phosphate (the substrate) to electro-active alpha naphtol (alpha-NAP, the product). alpha-NAP was oxidized at +0.23 V vs Ag/AgCl and this signal was measured by Differential Pulse Voltammetry (DPV). The signals obtained from alpha-NAP oxidation were compared for the probe and hybrid DNA. The specificity of the designed biosensor was proved by using non complementary sequences instead of complementary sequences and the detection limit of the assay was calculated to be 6 pmol for cell lysates. PMID- 22776182 TI - One more idea on preventable ICU deaths ... PMID- 22776184 TI - The evolution and adoption of standards used by AAALAC. AB - The Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) has operated its accreditation program for more than 45 y by using the Guide for the Care and Use of Laboratory Animals (the Guide) as a basic guide in the generation of accreditation standards. AAALAC supplements its reliance on the Guide with a number of documents, referred to as reference resources, that undergo a formal review and adoption process by AAALAC. Two reference resources have grown in importance to the accreditation process over the past decade as institutions from outside of the United States have increasingly sought accreditation and as greater numbers of agricultural animals are used in research programs. These 2 reference resources were the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, Council of Europe (ETS 123), and the Guide for the Care and Use of Agricultural Animals in Research and Teaching (Ag Guide). During the past 2 y, the Guide, Ag Guide, and ETS 123 were revised, prompting AAALAC to reevaluate these resources to determine the role each should play in the development of standards used for accreditation by AAALAC. As a result of AAALAC's review and analysis, the organization has adopted these 3 documents as primary standards. This article summarizes AAALAC's processes for the review, adoption, and implementation of these standards offering insights into the application of these standards in the accreditation process. PMID- 22776185 TI - Review of the third edition of the Guide for the Care and Use of Agricultural Animals in Research and Teaching. AB - The third edition (January 2010) of the Guide for the Care and Use of Agricultural Animals in Research and Teaching (the Ag Guide) was the collaborative effort of a group of 64 authors and provides a science-based reference and performance-based guidelines for institutions that use agricultural species in research and teaching. The adoption of the Ag Guide by the AAALAC Board of Trustees as a primary standard signifies its importance in the AAALAC accreditation process. PMID- 22776186 TI - The Animal Welfare Act: from enactment to enforcement. AB - Originally enacted in 1966, the Laboratory Animal Welfare Act has been amended several times and renamed the Animal Welfare Act. Responsibility for administering the Animal Welfare Act was delegated within the United States Department of Agriculture to the Administrator of the Animal and Plant Health Inspection Service, and regulations and standards have been developed to implement the intent of Congress conveyed in the language of the Act. In our opinion, the key to compliance with the Animal Welfare Act and its regulations and standards is to have in place a proactive, progressive Animal Care and Use Program that uses the semiannual inspection and programmatic review process to improve the day-to-day management of the program. Successfully managing the inspection process has taken on new meaning in what has recently become known as the 'Age of Enforcement.' As part of this approach, the Animal and Plant Health Inspection Service made changes to the inspection process and issued an Enhanced Animal Welfare Enforcement Plan, which included the development of an Inspection Requirements Handbook. The Inspection Requirements Handbook provides inspectors with information on conducting inspections and includes as an attachment a flow chart for Enforcement Action Guidance. The chart describes 4 types of actions that may occur as part of the enforcement process and the steps that will be followed if noncompliant items are documented during an inspection. PMID- 22776187 TI - The effect of public disclosure laws on biomedical research. AB - The Freedom of Information Act (FOIA) and state 'open-records' laws govern access to records in the possession of federal agencies and state entities, such as public universities. Although these laws are intended to promote 'open government' and to assure the existence of an informed citizenry capable of holding government officials accountable for their decisions, an inherent tension exists between the public's access to information and biomedical research institutions' need to ensure the confidentiality of proprietary records and to protect the personal safety of employees. Recognizing these and other conflicts, the federal FOIA and state public-disclosure laws contain express exemptions to protect sensitive information from disclosure. Although some state open-records laws are modeled after the federal FOIA, important differences exist based on the language used by the state law, court interpretations, and exemptions. Two specific types of exemptions are particularly relevant to research facilities: exemptions for research information and exemptions for personal information. Responding to FOIA and state open-records requests requires knowledge of relevant laws and the involvement of all interested parties to facilitate a coordinated and orderly response. PMID- 22776188 TI - FELASA guidelines and recommendations. AB - The Federation of European Laboratory Animal Science Associations (FELASA) has been releasing guidelines and recommendations on several laboratory animal science disciplines for more than 15 y. The Working Groups producing these documents comprise specialists in each of the addressed topics, are nominated by the FELASA constituent associations, and are elected by the FELASA Board of Management. The FELASA guidelines and recommendations are not regulatory but rather are proposals based on scientific knowledge and the state of the art of laboratory animal science activities. Because they are supported by laboratory animal science associations that represent the vast majority of European professionals, these guidelines and recommendations have influenced the development of various regulatory requirements in Europe, including those related to education and training, routine laboratory animal activities, and animal health monitoring. Some reports fill existing gaps in the European legal framework or complement it. The Working Groups occasionally collaborate with other European organizations, thus enhancing the professional input and effect of the documents produced. The recently established AALAS-FELASA Liaison Body may result in future international cooperation that benefits laboratory animal science and welfare in a global context. PMID- 22776189 TI - Pain management standards in the eighth edition of the Guide for the Care and Use of Laboratory Animals. AB - The eighth edition Guide for the Care and Use of Laboratory Animals sets standards for diverse laboratory animal care and use practices. It frames its standards as performance, engineering, and practice standards, with a strong emphasis on performance standards, allowing for multiple routes to clearly defined outcomes. Standards intended to be upheld rigorously are indicated through the use of must in the description, and those accommodating more flexibility are indicated through may and should statements. With respect to pain management standards, a fourth type of standard-the jurisdictional standard-has been prevalent through all 8 editions of the Guide. Under jurisdictional standards, specific methods and outcomes for measuring, preventing, or alleviating pain are not detailed, but the various jurisdictions of veterinarian, investigator, and IACUC are elaborated. Although data on pain management in laboratory animals has expanded greatly since the 1996 Guide, the eighth (2011) edition does not contain major new standards or guidance regarding animal pain management. Requirements for veterinary and IACUC involvement remain as in prior editions, and the duty of veterinarians and scientists to stay abreast of new developments is expected to drive refinement of animal pain management institution by institution. The current article details selected specific pain management standards in the 2011 Guide, lists topics in pain management for which the Guide does not set clear standards, and suggests possible standards for those topics. PMID- 22776190 TI - Aquatic environment, housing, and management in the eighth edition of the Guide for the Care and Use of Laboratory Animals: additional considerations and recommendations. AB - The eighth edition of the Guide for the Care and Use of Laboratory Animals recognizes the widespread use of aquatic and semiaquatic research animals by including, among other references, an entire section on aquatic animals in its chapter on environment, housing, and management. Recognizing the large number of aquatic and semiaquatic species used in research and the inherent diversity in animal needs, the Guide refers the reader to texts and journal reviews for specific recommendations and suggests consultations with persons experienced in caring for aquatic species. Here we present considerations that may add to the basic information presented in the Guide and offer some recommendations that may be useful for aquatic animal model caregivers and researchers. PMID- 22776191 TI - Select agent and toxin regulations: beyond the eighth edition of the Guide for the Care and Use of Laboratory Animals. AB - In the interval between the publication of the seventh and eighth editions of the Guide for the Care and Use of Laboratory Animals (Guide), much has changed with regard to the regulation and funding of highly pathogenic biologic agents and toxins (Select Agents). Funding of research involving highly pathogenic agents has increased dramatically during this time, thus increasing the demand for facilities capable of supporting this work. The eighth edition of the Guide briefly mentions Select Agents and provides a limited set of references. Here we provide some background information regarding the relevant laws and regulations, as well as an overview of the programmatic requirements pertaining to the use of Select Agents, with a focus on use in animals. PMID- 22776192 TI - Effects of cage enrichment on heart rate, blood pressure, and activity of female Sprague-Dawley and spontaneously hypertensive rats at rest and after acute challenges. AB - Here we sought to determine whether a nonsocial cage enrichment program, identical to one we previously used with male rats, was effective in reducing heart rate or systolic blood pressure (SBP) in female Sprague-Dawley rats and spontaneously hypertensive rats (SHR). Young adult rats, each instrumented with a radiotelemetry pressure transmitter, were housed individually under enriched or nonenriched conditions. Heart rate and SBP were monitored at 5- and 1-min intervals, respectively, when the rats were undisturbed or after several different types of experimental manipulations some of which are considered stressful. Cage enrichment did not significantly alter heart rate or SBP of undisturbed rats in either strain at any time during the day or night. However, activity of female SHR was increased in the afternoon and at night under enriched conditions compared with nonenriched conditions. The enrichment program did not significantly reduce heart rate or SBP responses to most acute manipulations in either strain. However, cage enrichment increased the responses to some procedures (Sprague-Dawley: handling, 1-h restraint; SHR: subcutaneous injection, tail-vein injection, handling). We conclude that a nonsocial cage enrichment program did not reduce physiologic indicators of stress in female Sprague-Dawley rats or SHR. PMID- 22776193 TI - Validation studies on blood collection from the jugular vein of conscious mice. AB - A method for blood collection from the jugular vein of mice without anesthesia was compared with a tail-incision technique. Jugular vein blood collection allowed withdrawal of almost 15% of the circulating blood volume at a time in less than 1 min. Hemolysis, hematocrit, and plasma thrombin-antithrombin complexes (a marker of blood coagulation) were higher in samples collected from the tail vein than the jugular vein. Mice produced similar plasma corticosterone levels after serial blood collection by either method. Tail incision led to a slight but significant increase in C-reactive protein levels. Using the jugular venipuncture technique, we then performed a pharmacokinetic study and an oral glucose tolerance test. Plasma concentrations of levofloxacin, an antimicrobial agent, were dose-dependently elevated after oral administration, and linear increases in C(max) and AUC were observed. We also confirmed that overall glucose excursion is significantly decreased in mice treated with exendin 4, a glucagon like peptide 1 agonist. These results indicate that the jugular venipuncture is a useful technique from the point of view of no requirement for anesthetics, serial blood collection at short intervals, large volume of blood collection, quality of sample and animal welfare. This technique is of particular interest for studies that examine time-dependent changes in blood variables. PMID- 22776194 TI - Assessing cervical dislocation as a humane euthanasia method in mice. AB - Research investigators often choose to euthanize mice by cervical dislocation (CD) when other methods would interfere with the aims of a research project. Others choose CD to assure death in mice treated with injected or inhaled euthanasia agents. CD was first approved for mouse euthanasia in 1972 by the AVMA Panel on Euthanasia, although scientific assessment of its humaneness has been sparse. Here we compared 4 methods of spinal dislocation--3 targeting the cervical area (CD) and one the thoracic region--in regard to time to respiratory arrest in anesthetized mice. Of the 81 mice that underwent CD by 1 of the 3 methods tested, 17 (21%) continued to breathe, and euthanasia was scored as unsuccessful. Postmortem radiography revealed cervical spinal lesions in 5 of the 17 cases of unsuccessful CD euthanasia. In addition, 63 of the 64 successfully euthanized mice had radiographically visible lesions in the high cervical or atlantooccipital region. In addition, 50 of 64 (78%) mice euthanized successfully had radiographically visible thoracic or lumbar lesions or both. Intentionally creating a midthoracic dislocation in anesthetized mice failed to induce respiratory arrest and death in any of the 18 mice subjected to that procedure. We conclude that CD of mice holds the potential for unsuccessful euthanasia, that anesthesia could be valuable for CD skills training and assessment, and that postmortem radiography has minimal promise in quality-control assessments. PMID- 22776196 TI - Evaluation of the safety and efficacy of recombinant factor IX (nonacog alfa) in minimally treated and previously treated Chinese patients with haemophilia B. PMID- 22776195 TI - Effects of buprenorphine on a cecal ligation and puncture model in C57BL/6 mice. AB - Sepsis research relies heavily on animal models. One of the most frequently used models, cecal ligation and puncture (CLP), involves surgery, and animal use committees may require the use of analgesics after CLP. However, some analgesics are immunomodulatory and may affect research outcomes. In addition, both septic inflammation and responses to opioids may vary with the sex of the subject. Therefore, we investigated the effects of buprenorphine in inbred mice of both sexes undergoing CLP. We hypothesized that buprenorphine would not significantly change the outcome or patterns of inflammation in C57BL/6 mice after CLP. Male and female C57BL/6 mice underwent CLP surgery and were randomized into 2 groups to receive either buprenorphine or saline. Three-week survival studies were performed (n = 20 per group). Survival did not differ between groups of female mice, but male mice that received buprenorphine had decreased survival compared with that of controls. Reducing the dose of buprenorphine in male mice ameliorated the difference in survival. To examine inflammation, mice (n = 10 per group) were euthanized at 12, 24, or 48 h after CLP. Cell counts and cytokines were measured in the blood and peritoneal lavage fluid. In female and male C57BL/6 mice, buprenorphine treatment resulted in few differences in inflammatory parameters, although peripheral neutrophil counts were decreased transiently in male mice. The findings suggest that the effects of buprenorphine on sepsis models in C57BL/6 mice may be sex-specific. Consequently the use of analgesics must be assessed on a study-by-study basis, and investigators should define analgesic regimens when publishing sepsis studies. PMID- 22776197 TI - Socioeconomic conditions of elderly people in Kosovo: a cross-sectional study. AB - BACKGROUND: Kosovo is the newest state in Europe facing a particularly difficult socioeconomic and political transition. The available evidence on socioeconomic conditions and quality of life of elderly people in Kosovo is scarce notwithstanding the ageing trend due to lowering of fertility rates and a higher life-expectancy. In this context, the aim of our study was to assess the socioeconomic conditions of elderly people in post-war Kosovo. METHODS: A cross sectional study was conducted in Kosovo in January-March 2011 including an age- sex-and residence (urban vs. rural)-stratified sample of 1,890 individuals (83.5% response) aged 65 years and over. A structured questionnaire included assessment of socio-demographic and socioeconomic characteristics including educational level and self-perceived poverty. Binary logistic regression was used to assess the association of self-perceived poverty with socio-demographic and socioeconomic factors. RESULTS: The educational level in this representative sample of elderly people in Kosovo was quite low, particularly among women. About 47% of respondents perceived themselves as poor, or extremely poor (41% of men and 52% of women). In multivariable-adjusted models, self-perceived poverty was higher among older women, low educated individuals, urban residents, and elderly individuals living alone. CONCLUSIONS: Findings from this study indicate that the socioeconomic situation of the elderly population in Kosovo is rather challenging. Demographic trends coupled with the economic and political transition raise serious concerns about increasing needs for socioeconomic support of elderly people in Kosovo. Specific policies and actions should be considered by a number of stakeholders, including government and civil society in transitional Kosovo. PMID- 22776198 TI - Moving forward in support of the IOM recommendations. PMID- 22776199 TI - Neurocardiogenic pulmonary oedema: initial presentation of multiple sclerosis. AB - A previously healthy 20 year-old male presented with headache, acute pulmonary oedema and left ventricular dysfunction requiring intensive care admission. Cardiorespiratory symptoms resolved within three days; however, the patient complained of persistent headache and had gait unsteadiness. Magnetic resonance imaging showed a large demyelinating lesion in the caudal medulla with scattered cerebral plaques. The patient was subsequently diagnosed with multiple sclerosis. This case describes a rare initial presentation of multiple sclerosis with acute pulmonary oedema and cardiac dysfunction secondary to a lower brainstem lesion. PMID- 22776200 TI - Impaired insulin signaling in an animal model of Niemann-Pick Type C disease. AB - Studies have shown similarities between the histopathological characteristics of NPC and Alzheimer's disease (AD) including amyloid and tau pathologies. While dysfunction in insulin signaling was widely detected in AD brain, the function of insulin signaling proteins has not been examined in NPC disease. In this study, we have examined the expression and phosphorylation of proteins linked to the insulin signaling pathway in the brain of 9 weeks old NPC(nih) mice. Our results showed lower expression of insulin receptor substrate 2 (IRS2) in the NPC(nih) mice, and insulin receptor substrate 1 (IRS1) expression was almost non detectable in this NPC mouse model. This reduction was associated with the loss of expression for the regulatory p85 subunit of phosphatidylinositol 3-kinase (p85/PI3K). Interestingly, the impairment was observed to link to a greater reduction of Akt phosphorylation at residue T308 than S473. This aberrant Akt phosphorylation could be contributing to lower GSK3beta phosphorylation detected in the NPC(nih) mouse brain. To our knowledge, this is the first report documenting impaired insulin signaling in the brain of a NPC mouse model. PMID- 22776201 TI - Phosphorylation of alpha-synuclein is crucial in compensating for proteasomal dysfunction. AB - alpha-Synuclein can be degraded by both the ubiquitin-proteasomal system and the chaperone-lysosomal system. However, the switching mechanism between the two pathways is not clearly understood. In our study, we investigated the mutual association between the binding of alpha-synuclein to heat shock cognate 70 and the lysosomal translocation of alpha-synuclein. Tyrosine phosphorylation of Y136 on alpha-synuclein increased when it bound to heat shock protein 70. We also found that tyrosine phosphorylation of alpha-synuclein can be regulated by focal adhesion kinase pp125 and protein tyrosine phosphatase 1B. Furthermore, protein tyrosine phosphatase 1B inhibitor protected dopaminergic neurons against cell death and rescued rotarod performance in a Parkinson's disease animal model. This study provides evidence that the regulation of Y136 phosphorylation of alpha synuclein can improve behavioral performance and protect against neuronal death by promoting the turnover of lysosomal degradation of alpha-synuclein. As a result, protein tyrosine phosphatase 1B inhibitor may be used as a potential therapeutic agent against Parkinson's disease. PMID- 22776202 TI - 3-O-sulfated glucuronide derivative as a potential anti-dengue virus agent. AB - A series of 12 carbohydrate compounds were synthesized by introduction of a sulfated group at specific positions and evaluated for their activities against dengue virus (DENV) infection as well as binding to BHK-21 cells. 3-O-sulfated GlcA was active against DENV infection, whereas 2-O-sulfated GlcA and 3,6-di-O sulfated Glc showed negligible activity. Persulfated compounds did not inhibit DENV infection. These results provided a rationale for designing sulfated carbohydrate compounds with low molecular mass as anti-DENV agents targeting E protein functions. 3-O-Sulfated GlcA showed no significant cytotoxicity at 1mM. The EC(50) value (120 MUM) was lower than that of sucrose octasulfate (SOS), a small molecular weight inhibitor of DENV infection. Two negatively charged groups, 3-O-sulfate and 6-C-carboxylic acid, appear to be essential for anti-DENV activity. We performed docking study to investigate the binding potential of 3-O sulfated GlcA with respect to DENV E protein. The docking study showed that distance and conformation of these negative charges on the carbohydrate may be suitable for association with three amino acid residues of E protein critically involved in virus adsorption (Lys295, Ser145, and Gly159). This interaction may competitively prevent functional DENV binding to receptor(s) on host cells. In conclusion, 3-O-sulfated GlcA is a chemical probe that may facilitate exploration of the molecular mechanisms underlying manifestations of dengue diseases. PMID- 22776203 TI - Diverse lectin-binding specificity of four ZP3 glycoprotein isoforms with a discrete isoelectric point in chicken egg coat. AB - The vertebrate egg coat corresponding to mammalian zona pellucida is a filamentous matrix composed of highly and heterogeneously glycosylated proteins designated ZP glycoproteins including ZP1 to 4, ZPD and ZPAX, and play important roles in species-specific egg-sperm interactions. Recent advance in structural biology of chicken ZP3 provided new insights into molecular mechanisms of the egg coat function involving its carbohydrate moieties. In this study, chicken ZP3 was separated into four major and distinct isoforms with different pI in 2D-PAGE. To investigate the meanings of the ZP3 heterogeneity in egg-sperm interactions, we preliminary analyzed glycan diversity on the molecules by using lectin-staining assays. The four major ZP3 isoforms 4-7 (from acidic to basic) were recognized equally with PNA (Galbeta1-3GalNAc), but the isoforms 5-7 were recognized dominantly with WGA ((beta-GlcNAc)n, clustered Sia), PHA-E (bi- and triantennary N-glycan containing Galbeta1-4GlcNAcbeta1-2Manalpha1-6) and RCA I (terminal Galbeta1-4GlcNAc), respectively. Despite such sugar chain diversity among the ZP3 isoforms, a partner in the egg coat, ZP1, showed specific binding to each isoform equally. Localization of ZP1 and ZP3 in the egg-coat matrix were also analyzed. PMID- 22776204 TI - Inhibition of histone acetylation by curcumin reduces alcohol-induced expression of heart development-related transcription factors in cardiac progenitor cells. AB - Alcohol exposure during pregnancy may cause congenital heart disease (CHD). In our previous studies, we found that alcohol selectively increased acetylation of histone H3 at lysine 9 (H3K9) and enhanced the expression of heart development related genes in cardiac progenitor cells. The objective of this study is to investigate the protective effects of histone acetyltransferases (HATs) inhibitor, curcumin, on histone hyperacetylation and the over-expression of heart development genes induced by alcohol. Western blot analysis was employed to detect the acetylation levels of histone H3K9 and real-time PCR was applied to measure the expressions of heart development-related transcription factors, GATA4, Mef2c and Tbx5 (GMT). Our results showed that alcohol increased the acetylation of H3K9 by 2.76-fold (P<0.05) and significantly enhanced the expression of GATA4 and Mef2c (P<0.05). When cells were treated with alcohol plus 25 MUM curcumin, the hyperacetylation of H3K9 and over-expression of GATA4 and Mef2c by alcohol was reversed. These data indicate that curcumin can correct the over-expression of cardiac genes by reversing the alcohol induced hyperacetylation of histone H3 at lysine 9 in cardiac progenitor cells, suggesting that curcumin is protective against alcohol-induced cardiac gene over expression that may result in heart malformations. PMID- 22776205 TI - Angiotensin II induces apoptosis in intestinal epithelial cells through the AT2 receptor, GATA-6 and the Bax pathway. AB - Angiotensin II (Ang II) has been shown to play an important role in cell apoptosis. However, the mechanisms of Ang-II-induced apoptosis in intestinal epithelial cells are not fully understood. GATA-6 is a zinc finger transcription factor expressed in the colorectal epithelium, which directs cell proliferation, differentiation and apoptosis. In the present study we investigated the underlying mechanism of which GATA-6 affects Ang-II induced apoptosis in intestinal epithelial cells. The in vitro intestinal epithelial cell apoptosis model was established by co-culturing Caco-2 cells with Ang II. Pretreatment with Angiotensin type 2 (AT2) receptor antagonist, PD123319, significantly reduced the expression of Bax and prevented the Caco-2 cells apoptosis induced by Ang II. In addition, Ang II up-regulated the expression of GATA-6. Interestingly, GATA-6 short hairpin RNA prevented Ang II-induced intestinal epithelial cells apoptosis and reduced the expression of Bax, but not Bcl-2. Taken together, the present study suggests that Angiotensin II promotes apoptosis in intestinal epithelial cells through GATA-6 and the Bax pathway in an AT2 receptor-dependent manner. PMID- 22776206 TI - Mesenchymal stem cells for cartilage repair in osteoarthritis. AB - Osteoarthritis (OA) is a degenerative disease of the connective tissue and progresses with age in the older population or develops in young athletes following sports-related injury. The articular cartilage is especially vulnerable to damage and has poor potential for regeneration because of the absence of vasculature within the tissue. Normal load-bearing capacity and biomechanical properties of thinning cartilage are severely compromised during the course of disease progression. Although surgical and pharmaceutical interventions are currently available for treating OA, restoration of normal cartilage function has been difficult to achieve. Since the tissue is composed primarily of chondrocytes distributed in a specialized extracellular matrix bed, bone marrow stromal cells (BMSCs), also known as bone marrow-derived 'mesenchymal stem cells' or 'mesenchymal stromal cells', with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. BMSCs can be easily isolated and massively expanded in culture in an undifferentiated state for therapeutic use. Owing to their potential to modulate local microenvironment via anti-inflammatory and immunosuppressive functions, BMSCs have an additional advantage for allogeneic application. Moreover, by secreting various bioactive soluble factors, BMSCs can protect the cartilage from further tissue destruction and facilitate regeneration of the remaining progenitor cells in situ. This review broadly describes the advances made during the last several years in BMSCs and their therapeutic potential for repairing cartilage damage in OA. PMID- 22776207 TI - Repeat 2-week wait referrals for colorectal cancer. AB - AIM: The inappropriate use of the '2-week wait' pathway for suspected colorectal cancer (CRC2ww) may overload urgent clinics and delay the assessment and investigation of other patients. Those who have been previously referred and investigated for suspected colorectal cancer may present one group that does not warrant repeat urgent referral. This paper aims to identify the incidence and diagnostic yield of repeat CRC2ww referrals. METHOD: All CRC2ww patients referred to our unit over a 4-year period were identified retrospectively. Referral indication, outcome and instances of repeat referral were identified from multidisciplinary team, endoscopy and imaging databases. RESULTS: In all, 2735 CRC2ww referrals were made over the study period. Of these, 122 were repeated CRC2ww referrals, with the incidence increasing from 2% in 2008 to 6% in 2010 (P = 0.0006). The median time to repeat referral was 1070 days. After initial referral 267 cancers were detected, including 212 colorectal cancers. The diagnostic yield was lower but not significantly so after repeated referral (six cancers) compared with initial referral (5%vs 10%, P = 0.07). CONCLUSION: The incidence of repeat referral is low but the diagnostic yield is not insignificant. Exclusion of these patients from urgent assessment and investigation will not significantly reduce workload and may risk missing some patients with cancer. PMID- 22776208 TI - Trypanosoma brucei transferrin receptor can bind C-lobe and N-lobe fragments of transferrin. AB - Transferrin (Tf) is a dumbbell-shaped iron transport protein composed of two homologous lobes (C-lobe and N-lobe) and is an essential growth factor for the protozoan parasite Trypanosoma brucei. The trypanosomal receptor for Tf uptake (TbTfR) is a heterodimeric complex that bears no structural similarity with the human Tf receptor. As a first step in identifying the region of Tf involved in binding to the TbTfR, C-lobe and N-lobe fragments were assessed for their capability to interact with the receptor. Preparations of C-lobe and N-lobe fragments were obtained by digestion of iron-loaded bovine Tf with proteinase K agarose. The individual fragments were then purified by concanavalin A affinity chromatography. Uptake experiments with bloodstream forms of T. brucei demonstrated that both C-lobe and N-lobe fragments were ingested by the parasites. The uptake of the isolated lobes could be inhibited by an excess of Tf and vice versa. Dot blot binding assays showed that both C-lobe and N-lobe fragments were capable of binding to the TbTfR. Both isolated lobes were also able to support the growth of bloodstream forms of T. brucei when cultured in Tf depleted medium. However, the C-lobe fragment was more efficiently taken up and more potent in supporting parasite growth. The results indicate that the interaction of Tf with the TbTfR is different from that with the human Tf receptor. This difference may be exploited for the development of agents specifically interfering with the binding of Tf to the TbTfR. PMID- 22776209 TI - Mass transfer in a membrane aerated biofilm. AB - We present experimental results of mass transfer of a non reactive tracer gas (neon) measured in aerobic heterotrophic biofilm developed from activated sludge. Biofilms are grown in various hydrodynamic conditions and the effective diffusivity is used to quantify the mass transfer through the biofilm. Beyond some cross-flow conditions, the effective diffusivity through the biofilm seems larger than in the bulk. This can be explained by a dispersion generated by convection inside the biofilm, as supported by an analytical flow model and in accordance to the numerical simulation proposed by Aspa et al. (2011). PMID- 22776210 TI - Aerobic sludge granulation: a tale of two polysaccharides? AB - Aerobic sludge granules are suspended biofilms with the potential to reduce the cost and footprint of secondary wastewater treatment. Attempts to answer how and why they form leads to a consideration of the role of their extracellular polymeric substances (EPS) in determining their physical and microbiological properties. The exopolysaccharide components of this matrix, in particular, have received attention as putative structural, gel-forming agents. Two quite different exopolysaccharides have been proposed as the gel-forming constituents, with their gel properties clearly different from those of activated sludge EPS. This review aims to address the question of whether more than one gel-forming exopolysaccharide exist in granules. Based on the available structural data, it seems likely that they are different gel-forming polymers and their differences are not artifacts of the analytical methods used. Nonetheless, both proposed structural gel polymers are extracted and purified based on procedures selecting for anionic polar polysaccharides soluble at high pH, and both contain hexuronic acids. Granulation does not result from EPS synthesis by any single microbial population, nor from production of a single exopolysaccharide. Future studies using solvents suitable for recalcitrant polysaccharides are likely to reveal important structural roles for other polysaccharides. It is hoped that this article will serve as a guide for subsequent studies into understanding the roles of exopolysaccharides in aerobic granular sludge. PMID- 22776212 TI - New fossil species of ommatids (Coleoptera: Archostemata) from the Middle Mesozoic of China illuminating the phylogeny of Ommatidae. AB - BACKGROUND: Ommatidae is arguably the "most ancestral" extant beetle family. Recent species of this group are only found in South America and Australia, but the fossil record reveals a much broader geographical distribution in the Mesozoic. Up to now, thirteen fossil genera with more than 100 species of ommatids have been described. However, the systematic relationships of the extant and extinct Ommatidae have remained obscure. Three constraint topologies were designed based on Kirejtshuk's hypothesis, enforced the monophyly of Tetraphalerus + Odontomma, Pareuryomma + Notocupes and both respectively. RESULTS: In this study, four new species, Pareuryomma ancistrodonta sp. nov., Pareuryomma cardiobasis sp. nov., Omma delicata sp. nov., and Tetraphalerus decorosus sp. nov., are described. Based on well-preserved fossil specimens and previously published data the phylogenetic relationships of extant and extinct lineages of Ommatidae were analyzed for the first time cladistically. Based on the results we propose a new classification with six tribes of Ommatidae: Pronotocupedini, Notocupedini, Lithocupedini, Brochocoleini, Ommatini and Tetraphalerini. These taxa replace the traditional four subfamilies. CONCLUSION: There is good support for the monophyly of the ingroup. Notocupedini, as defined by Ponomarenko, are paraphyletic. Notocupoides + Eurydictyon are the sister group of the remaining fossil and extant ommatids. Together they form the clade Pronotocupedini. Notocupedini and Lithocupedini are the next two branches. The tribe Brochocoleini is the sister group of a clade comprising Tetraphalerini and Ommatini. PMID- 22776211 TI - Oncocytic-type intraductal papillary mucinous neoplasm (IPMN)-derived invasive oncocytic pancreatic carcinoma with brain metastasis - a case report. AB - Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC) and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis. PMID- 22776213 TI - Anti-inflammatory activity of sublingual immunoglobulin (SLIG) in a murine model of allergen-driven airway inflammation. AB - AIM: Intravenous immunoglobulin (IVIG) displays anti-inflammatory activities in many diseases. Subcutaneous administration of anti-IgE in humans provides benefit in severe persistent allergic asthma. Given the well established efficacy of sublingual allergen immunotherapy in respiratory type I allergies, we investigated the therapeutic potential of sublingual immunoglobulin (SLIG), most particularly anti-IgE SLIG, in a murine model of allergen-driven airway inflammation. METHODS: BALB/c mice sensitized with ovalbumin (OVA) were treated sublingually with rat monoclonal IgG1 or IgG2a, either directed to mouse IgE or with no reported specificity. Airway hyperresponsiveness (AHR) was assessed by whole body plethysmography, and eosinophil infiltrates were characterized in bronchial alveolar lavages (BAL). OVA-specific antibody and T cell responses were analyzed in sera and saliva or lung and draining lymph nodes, by ELISA or CBA measurement of cytokine production, respectively. RESULTS: AHR and BAL eosinophil infiltrates were substantially decreased in mice treated sublingually with particulate OVA (positive control), as well as in animals receiving various rat IgG1, irrespective of their specificity for murine IgE. In contrast, no improvement was observed in mice treated with PBS (negative control) or various rat IgG2a. SLIG anti-inflammatory activity is not related to a downregulation of Th2, Th17 or an induction of Foxp3(+) CD4(+) regulatory T cell responses. Mass spectrometry analysis of glycan moieties, such as sialic acid, suggests that the differential efficacy of rat IgG1 and IgG2a is not related to their capacity to interact with lectins borne by oral immune cells. CONCLUSIONS: In a murine model of allergen-driven airway inflammation, SLIG exhibits an anti-inflammatory activity irrespective of the immunoglobulin specificity, and in the absence of allergen. As a noninvasive approach, SLIG deserves to be further studied as a treatment for other inflammatory diseases beyond allergic asthma. PMID- 22776215 TI - Risk factors for low vaccination coverage among Roma children in disadvantaged settlements in Belgrade, Serbia. AB - BACKGROUND: Full vaccination coverage for children under 59 months of age in Serbia is over 90%. This study assesses vaccination coverage and examines its association with birth registration among Roma children who resided in disadvantaged settlements in Belgrade, Serbia. METHODS: The First Roma Health and Nutrition Survey in Belgrade settlements, 2009, was conducted among households of 468 Roma children between the ages of 6-59 months. The 2005 WHO Immunization Coverage Cluster Survey sampling methodology was employed. Vaccinations were recorded using children's vaccination cards and through verification steps carried out in the Primary Health Care Centers. For those who had health records the information on vaccination was recorded. RESULTS: About 88% of children had vaccination cards. The mean rate of age appropriate full immunization was 16% for OPV and DTP and 14.3% for MMR. Multivariate analyses indicated that children whose births were registered with the civil authorities were more likely to have their vaccination cards [OR=6.1, CI (2.5, 15.0)] and to have their full, age appropriate, series vaccinations for DTP, OPV, MMR and HepB [OR=3.8, CI (1.5, 10.0), OR=3.2, CI (1.5, 6.6), OR=4.8, CI (1.1, 21.0), OR=5.4, CI (1.4, 21.6), respectively]. CONCLUSIONS: The immunization coverage among Roma children in settlements is far below the WHO/UNICEF MDG4 target in achieving prevention and control of vaccine preventable diseases. It demonstrates the need to include "invisible" populations into the health systems in continuous, integrated, comprehensive, accessible and sensitive modes. PMID- 22776214 TI - Live attenuated rubella viral vectors stably express HIV and SIV vaccine antigens while reaching high titers. AB - Live attenuated viruses make potent and effective vaccines. Despite the urgent need for an HIV vaccine, this approach has not been feasible, since it has not been possible to attenuate the virus reliably and guarantee vaccine safety. Instead, live viral vectors have been proposed that could present HIV vaccine antigens in the most immunogenic way, in the context of an active infection. We have adapted the rubella vaccine strain RA27/3 as a vector to express HIV and SIV antigens, and tested the effect of insert size and composition on vector stability and viral titer. We have identified an acceptor site in the rubella nonstructural gene region, where foreign genes can be expressed as a fusion protein with the nonstructural protein P150 without affecting essential viral functions. The inserts were expressed as early genes of rubella, under control of the rubella genomic promoter. At this site, HIV and SIV antigens were expressed stably for at least seven passages, as the rubella vectors reached high titers. Rubella readily infects rhesus macaques, and these animals will provide an ideal model for testing the new vectors for replication in vivo, immunogenicity, and protection against SIV or SHIV challenge. PMID- 22776217 TI - An investigation of the affinities, specificity and kinetics involved in the interaction between the Yin Yang 1 transcription factor and DNA. AB - Human transcription factor Yin Yang 1 (YY1) is a four zinc-finger protein that regulates a large number of genes with various biological functions in processes such as development, carcinogenesis and B-cell maturation. The natural binding sites of YY1 are relatively unconserved and have a short core sequence (CCAT). We were interested in determining how YY1 recognizes its binding sites and achieves the necessary sequence selectivity in the cell. Using fluorescence anisotropy, we determined the equilibrium dissociation constants for selected naturally occurring YY1 binding sites that have various levels of similarity to the consensus sequence. We found that recombinant YY1 interacts with its specific binding sites with relatively low affinities from the high nanomolar to the low micromolar range. Using a fluorescence anisotropy competition assay, we determined the affinity of YY1 for non-specific DNA to be between 30 and 40 MUm, which results in low specificity ratios of between 3 and 220. Additionally, surface plasmon resonance measurements showed rapid association and dissociation rates, suggesting that the binding strength is regulated through changes in both k(a) and k(d). In conclusion, we propose that, in the cell, YY1 may achieve higher specificity by associating with co-regulators or as a part of multi subunit complexes. PMID- 22776216 TI - A randomised, double-blind, non-inferiority clinical trial on the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis (TdaP) vaccine in comparison to a tetanus and diphtheria (Td) vaccine when given as booster vaccinations to healthy adults. AB - BACKGROUND: Increasing incidence of pertussis in adolescents and adults has stimulated the development of safe and immunogenic acellular pertussis vaccines for booster vaccination of adolescents and adults. PURPOSE: To obtain clinical documentation of the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis combination vaccine (TdaP), when given as a booster vaccination to adults. METHODS: The trial was double-blind, controlled and randomised. 802 healthy adults, aged 18-55 years who had completed childhood vaccination with diphtheria, tetanus and whole cell pertussis vaccine (DTwP), were booster vaccinated with TdaP or Td. Blood samples were taken before and one month after the vaccination for serological analysis and adverse events were recorded during the one-month-follow-up period. RESULTS: The monocomponent acellular pertussis vaccine (aP) in the TdaP vaccine was immunogenic in adults with 92.0% of TdaP vaccinated subjects obtaining an anti-pertussis toxin (anti PT) antibody booster response. TdaP was non-inferior to Td in eliciting seroprotective anti-tetanus and diphtheria antibody concentrations with more than 98% of subjects obtaining post-vaccination seroprotective concentrations (>= 0.1 IU/mL). T and d booster response rates were 93.0% and 97.5%, respectively. The frequencies of solicited local adverse reactions were low and comparable between TdaP and Td vaccinees. In the TdaP group, 30.7% reported pain, 4.2% swelling and 2.0% erythema at the injection site. The most frequent solicited general symptoms were headache (20.4%), fatigue (17.0%) and myalgia (10.0%). In the Td group, 35.7% reported pain, 2.5% swelling and 3.2% erythema at the injection site, whereas headache, fatigue and myalgia were reported by 15.7%, 14.5% and 12.5%, respectively. In conclusion, TdaP Vaccine SSI was safe and immunogenic when given as a booster vaccination to adults. PMID- 22776218 TI - Antiproliferative effects of lectins from Canavalia ensiformis and Canavalia brasiliensis in human leukemia cell lines. AB - The antiproliferative activity of lectins Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr) were studied using human leukemia MOLT-4 and HL-60 cell lines. It was revealed that both ConA and ConBr were markedly cytotoxic to cells using MTT and NAC assays. The IC(50) values were approximately 3 and 20 MUg/mL for ConA and ConBr, respectively, for both MOLT-4 and HL-60 cells. However, in normal human peripheral blood lymphocytes, the lectins were not cytotoxic, even when tested at concentrations as high as 200 MUg/ml. Using comet assay, the lectins produced a rate of DNA damage exceeding 80% in MOLT-4 and HL 60 cells. Fluorescence analysis revealed the morphology characteristic of apoptosis, with low concentrations of apoptotic bodies and fragmented DNA (5 MUg/ml). Flow cytometric analysis demonstrated an accumulation of cells in the sub-G1 cell cycle that is characteristic of DNA fragmentation, and a decrease in membrane integrity at high concentrations. Lastly, we evaluated the alterations in mitochondrial potential that reduced after treatment with lectins. Our results indicate that ConA and ConBr inhibited cell proliferation selectively in tumor cells and that apoptosis was the main death mechanism. Therefore, lectins can be considered a class of molecules with a high antitumor activity potential. PMID- 22776219 TI - Intraarticular hemorrhage due to bevacizumab in a patient with metastatic colorectal cancer: a case report. AB - INTRODUCTION: Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. It is widely used in the treatment of metastatic colorectal cancer. It has some specific side effects including severe bleeding, wound healing problems, gastrointestinal perforation, proteinuria and hypertension. CASE PRESENTATION: We present the case of a 65-year old Asian man with synovial metastasis of the knee who experienced intraarticular hemorrhage after bevacizumab treatment. He presented with monoarthritis of the left knee. CONCLUSION: Bevacizumab-related hemorrhage can cause serious morbidity and unusual sites of hemorrhage may be seen. PMID- 22776220 TI - Overview of methods for flexible endoscopic training and description of a simple explant model. AB - The question of how to train surgeons in flexible endoscopy has been debated over the years as these skills have become an essential part of residency and practice. As many as two-thirds of surgeons perform flexible endoscopy, and for many, endoscopy represents up to 50% of their practice. Training in flexible endoscopy has evolved over many decades from an apprenticeship-type model to a more formal training program. Surgical residencies vary widely in their approach, with some having dedicated endoscopy rotations and others using an integrated approach. Innate to a good training program are faculty dedicated to teaching, an established curriculum, and adequate exposure of residents to proper training tools, whether as patient-based learning or supplemented by simulators. Hands-on models for teaching surgical endoscopy include mechanical, animal, and computer based platforms. Herein, we describe our experience with a low-cost approach using porcine stomach explants that offers a breadth of endoscopic training including scope navigation, band ligation, endoscopic mucosal resection, hemostasis management, esophageal stenting, foreign body extraction, and ERCP. Simulation-based learning must be validated from a construct and internal validity perspective to be considered useful. Correlation between simulator learning and improvement in clinically relevant skills must then be shown using a validated scale, such as the Global Assessment of Gastrointestinal Endoscopy Skills. Competency in flexible endoscopy, which is currently measured by case volume, may be replaced by objective programs, such as Fundamentals of Endoscopic Surgery, that combine didactic teaching, cognitive assessment, and hands-on technical skills evaluation to determine a minimum level of proficiency. PMID- 22776221 TI - Managing concomitant gallbladder stones and common bile duct stones in the laparoscopic era: a systematic review. AB - BACKGROUND: There is still no consensus on the ideal management of common bile duct (CBD) stones. This article aims to review the management of concomitant gallbladder stones and CBD stones in the laparoscopic era. METHOD: A PubMed database search was performed to identify MEDLINE articles from 1986 to 2010 using the key terms "common bile duct stones,""cholecystectomy,""bile duct exploration,""ERCP" (endoscopic retrograde cholangiography), and "endoscopic sphincterotomy." RESULTS: There were five randomized comparative trials (RCT) comparing sequential preoperative ERCP and laparoscopic cholecystectomy (LC) to laparoscopic common bile duct exploration (LCBDE). Two RCTs showed similar stone clearance rates and shorter hospital stays in the LCBDE group, while three RCTs showed similar stone clearance rates and hospital stays in sequential preoperative ERCP, LC and LCBDE groups. There were two RCTs comparing LCBDE to sequential LC and postoperative ERCP. One showed similar stone clearance rate and shorter hospital stay in LCBDE group, while the other showed similar stone clearance rate and hospital stay. There were three RCTs comparing sequential preoperative ERCP and LC against LC with intraoperative ERCP. All three studies showed similar stone clearance rates and shorter hospital stays in the intraoperative ERCP group. There was only one RCT comparing sequential preoperative ERCP and LC against sequential LC and postoperative ERCP. This showed a similar stone clearance rate and shorter hospital stay in the postoperative ERCP group. CONCLUSION: Different management approaches of concomitant gallbladder stones and CBD stones were equivalent in efficacy. However, one-stage management had the advantage of providing a shorter hospital stay. PMID- 22776222 TI - Single-incision laparoscopic surgery: hernia repair. AB - In most countries, inguinal hernia repair is the most frequent procedure performed in a surgical practice. Different approaches have been developed during the last decades, with a strong tendency towards tension-free techniques. The laparoscopic approach offers advantages in terms of less postoperative pain and faster recovery with a low incidence in recurrence. In the last few years, single incision laparoscopic surgery (SILS) has been introduced to further improve surgical outcome and cosmetic results. For SILS inguinal hernia repair, there is little data available so far, but both totally extraperitoneal hernia repair and transabdominal preperitoneal hernia repair have been succesfully performed without complications in a limited number of patients. In our experience, totally extraperitoneal hernia repair seems to be an ideal indication for the application of SILS. PMID- 22776223 TI - Routine drainage is not necessary after laparoscopic gastric bypass. AB - INTRODUCTION: Routine intra-abdominal drainage has been recommended for detecting surgical complications, such as anastomotic leaks or intra-abdominal hemorrhage, after laparoscopic gastric bypass for morbid obesity. The aim of this study was to determine whether routine drainage after laparoscopic gastric bypass is indeed necessary. METHODS: Patients undergoing laparoscopic gastric bypass with intra abdominal drainage (D-group) were compared with those without drainage (N-group) in a retrospective study. The main outcome measures were postoperative course and complications. RESULTS: No differences were observed in the postoperative complications. Both groups had one major complication of leakage (1/90, 1.1%). Minor complications occurred in six D-group patients (6/90, 6.7%) and eight N group patients (8/90, 8.9%) (P=0.578). No difference was observed in postoperative analgesic dose usage (mean +/- SD: 63 +/- 37 mg vs 60 +/- 31 mg; P=0.963) or length of stay hospital (5.2 +/- 2.6 d vs 4.7 +/- 1.8 d; P=0.135). However, the N-group had a shorter time to flatus passage compared to the D-group (1.6 +/- 0.7 d vs 1.2 +/- 0.5 d; P=0.006). CONCLUSION: Routine abdominal drainage is not necessary after a successful laparoscopic gastric bypass for morbidly obese patients. Drainage omission may contribute to a quicker recovery without additional surgical complications. PMID- 22776224 TI - Safe anastomosis in laparoscopic low anterior resection for rectal cancer. AB - INTRODUCTION: In laparoscopic rectal surgery, there are some limitations on a surgeon's ability to maneuver, especially in transection of the lower rectum. To achieve minimally invasive surgery, safe anastomosis, including proper rectal transaction, is necessary. METHODS: To overcome the difficulty in lower rectal resection, we followed a series of steps. First, we completely mobilized the rectum to the pelvic bottom, just above the anal canal, making the lower rectum mobile and allowing for an easy rectal transection. To secure the transaction, the mesorectum around the transection must be properly divided. We recommend placing the lower right quadrant port as caudal as possible to properly staple the rectum. We found a 60 mm compression-type stapler most suitable for rectal transection. To wash and flatten the rectum, a detachable intestinal clip is quite useful because of its flexibility. Finally, in addition to conventional abdominal drains around the anastomotic site, we employed transanal tube to actively decompress rectal pressure inside the anastomotic site. RESULTS: Between August 2009 and July 2010, 101 patients underwent laparoscopic low anterior resection using this technique. Most patients, 98.0% (99/101), underwent lower rectum transection using a single-fire cartridge. The anastomotic leakage rate was only 1.0% (1/101) in total and 1.3% (1/78), when not including patients with diverting stoma. CONCLUSION: We have to follow up with more patients to conclude whether our technique is effective in the long term. However, this step-by-step technique could lead to safe anastomosis in laparoscopic low anterior resection for rectal cancer. PMID- 22776225 TI - Feasibility of fibrin glue versus endoclips to close the transgastric peritoneal access site in NOTES in a survival porcine study. AB - INTRODUCTION: Safe peritoneal access and gastric closure are the most important concerns in clinical applications of NOTES. Our past study demonstrated usefulness of the submucosal tunnel technique for safe peritoneal access and closure with endoclips. However, such closure is sometimes difficult and time consuming. This study investigated the feasibility of fibrin glue for submucosal tunnel closure in a NOTES porcine model. METHODS: In 10 female pigs each weighing 40 kg, transgastric peritoneoscopy was performed through a 60 mm-long submucosal tunnel created using the endoscopic submucosal dissection technique. After transgastric peritoneoscopy for 30 min, the submucosal tunnel was closed with endoclips in five pigs and fibrin glue in five pigs. After a 7 d follow-up period, the pigs were euthanized for post-mortem examination. Outcome measures included (a) technical feasibility of closure with endoclips versus fibrin glue, (b) clinical monitoring for 7 d, (c) follow-up necropsy at 7 d, and (d) histopathologic examination of the peritoneal access site. RESULTS: Transgastric peritoneoscopy with submucosal tunnel technique was successful in all pigs. Mean time required to close the mucosal incision site with fibrin glue was 1.6 +/- 0.5 versus 19 +/- 18.7 min with endoclips. All pigs survived well without complications. Necropsy revealed no peritonitis. There were no differences in transgastric peritoneal access sites between endoclips and fibrin glue. Histopathologic examination of the submucosal tunnel demonstrated wound healing with transmural fibrosis. No adverse effects from fibrin glue were noted. CONCLUSION: Compared with endoclips, the application of fibrin glue is easy and simple in the closure of transgastric peritoneal access in NOTES. PMID- 22776226 TI - Colonic cavernous hemangiomas: a report of two cases treated by laparoscopic surgery. AB - Hemangiomas are rare vascular tumors. They most commonly appear in the small bowel, as well as the colon and the rectum. Here, we report two cases of male patients who were admitted to our hospital for low rectal painless bleeding, misdiagnosed of hemorrhoid bleeding. Colonoscopy reported vascular tumors in both cases, which we surgically removed. PMID- 22776227 TI - Laparoscopic-assisted management of severe necrotizing pancreatitis with obstructive jaundice: a case report. AB - We report a severely infected necrotizing pancreatitis managed with hand-assisted laparoscopic necrosectomy along with a review of the relevant literature. Minimally invasive necrosectomy has been shown to be efficient and advantageous in managing necrotizing pancreatitis. Multiple techniques have been advocated over the last decade. Laparoscopic pancreatic debridement is a feasible option for some patients with necrotizing pancreatitis. We selected hand-assisted laparoscopic pancreatic necrosectomy, which has gained some favor over open necrosectomy because of the morbidity and mortality associated with laparotomy. We report on an Indian male patient who presented with acute abdomen and severe jaundice. A CT scan of the abdomen showed severe necrotizing pancreatitis. After conservative management failed, a hand-assisted laparoscopic pancreatic necrosectomy was performed. The patient recovered and was discharged 4 weeks after surgery. PMID- 22776228 TI - A case of thyroid-type papillary carcinoma derived from ovarian mature cystic teratoma, resected by laparoscopic surgery. AB - Follicular variant thyroid-type papillary carcinoma (FVTPC) arising from thyroid tissue in mature cystic teratoma of the left ovary is extremely rare, and it is not easy to diagnose preoperatively. However, with reports of an early postoperative death, we must prudently select the strategy for this lesion. A 50 year-old woman had a uterine fibroid with hypermenorrhea and a left ovarian tumor measuring approximately 8 cm diameter. Serum thyroid-stimulating hormone level was within the normal limit. A laparoscopic hysterectomy and left salpingo oophorectomy were performed. During surgery, there were no signs of invasion or metastasis, and there was no spillage in the abdomen. On histopathological examination of the left ovary, we diagnosed FVTPC arising from thyroid tissue in mature cystic teratoma of the left ovary. FVTPC in ovarian struma is a rare malignant transformation. We must be aware of the possibility of such a rare malignant disease when treating teratoma laparoscopically. PMID- 22776229 TI - Laparoscopy-assisted surgery for neonatal intestinal atresia: single-center experience(*). AB - INTRODUCTION: Neonatal intestinal atresia surgery requires careful assessment of bowel patency, resection of the affected bowel and a diligent anastomosis. Traditional anastomosis with sutures via a laparoscopic approach would lengthen the surgical time. Various minimally invasive techniques have been reported for neonatal surgery. Our technique offers improved benefits of laparoscopy while observing good principles of surgery. MATERIALS AND SURGICAL TECHNIQUE: Using a three-port approach to aid careful laparoscopic inspection of the bowel, we performed laparoscopy-assisted neonatal intestinal atresia repair in three term neonates with no cardiorespiratory compromise. Anastomosis was manually performed after exteriorzation of the bowel via the umbilical port site without any extension of the original port-site incision. There were no complications or conversions to open approach. DISCUSSION: Our technique is an improvement over previously reported limited/umbilical laparotomy approaches and blends the benefits of laparoscopy and open surgery most effectively. Careful bowel inspection and assessment of patency could be safely and systematically performed laparoscopically with limited exteriorization of the bowel for rapid hand-sewn anastomosis and without compromising bowel viability. A multicenter randomized trial will be useful to compare the open laparotomy approach with our technique. PMID- 22776230 TI - New minimally invasive discectomy technique through the interlaminar space using a percutaneous endoscope. AB - INTRODUCTION: The serial dilating technique used to access herniated discs at the L5-S1 space using percutaneous endoscopic discectomy (PED) via an 8 mm skin incision can possibly injure the S1 nerve root. In this paper, we describe in detail a new surgical procedure to safely access the disc and to avoid the nerve root damage. This small-incision endoscopic technique, small-incision microendoscopic discectomy (sMED), mimics microendoscopic discectomy and applies PED. MATERIALS AND SURGICAL TECHNIQUE: The sMED approach is similar to the well established microendoscopic discectomy technique. To secure the surgical field, a duckbill-type PED cannula is used. Following laminotomy of L5 using a high-speed drill, the ligamentum flavum is partially removed using the Kerrison rongeur. Using the curved nerve root retractor, the S1 nerve root is gradually and gently moved caudally. Following the compete retraction of the S1 nerve root to the caudal side of the herniated nucleus pulposus (HNP), the nerve root is retracted safely medially and caudally using the bill side of the duckbill PED cannula. Next, using the HNP rongeur for PED, the HNP is removed piece by piece until the nerve root is decompressed. A total of 30 patients with HNP at the L5-S1 level underwent sMED. In all cases, HNP was successfully removed and patients showed improvement following surgery. Only one patient complained of moderate radiculopathy at the final visit. No complications were encountered. DISCUSSION: We introduced a minimally invasive technique to safely remove HNP at the L5-S1 level. sMED is possibly the least invasive technique for HNP removal at the L5-S1 level. PMID- 22776232 TI - Role of chemotherapy in stage IIb nasopharyngeal carcinoma. AB - The efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy on stage IIb nasopharyngeal carcinoma(NPC) remains unclear. Conventional two-dimensional radiotherapy combined with concurrent chemotherapy can improve the overall survival, progression-free survival, recurrence-free survival, and distant metastasis-free survival of patients with stage IIb NPC. Intensity-modulated radiotherapy without concurrent chemotherapy also provides good outcomes for patients with stage IIb NPC. This article summarizes the features of stage IIb NPC and reviews the role of chemotherapy in this subgroup of NPC. PMID- 22776231 TI - Interest of a simple on-line screening registry for measuring ICU burden related to an influenza pandemic. AB - INTRODUCTION: The specific burden imposed on Intensive Care Units (ICUs) during the A/H1N1 influenza 2009 pandemic has been poorly explored. An on-line screening registry allowed a daily report of ICU beds occupancy rate by flu infected patients (Flu-OR) admitted in French ICUs. METHODS: We conducted a prospective inception cohort study with results of an on-line screening registry designed for daily assessment of ICU burden. RESULTS: Among the 108 centers participating to the French H1N1 research network on mechanical ventilation (REVA) - French Society of Intensive Care (SRLF) registry, 69 ICUs belonging to seven large geographical areas voluntarily participated in a website screening-registry. The aim was to daily assess the ICU beds occupancy rate by influenza-infected and non infected patients for at least three weeks. Three hundred ninety-one critically ill infected patients were enrolled in the cohort, representing a subset of 35% of the whole French 2009 pandemic cohort; 73% were mechanically ventilated, 13% required extra corporal membrane oxygenation (ECMO) and 22% died. The global Flu OR in these ICUs was only 7.6%, but it exceeded a predefined 15% critical threshold in 32 ICUs for a total of 103 weeks. Flu-ORs were significantly higher in University than in non-University hospitals. The peak ICU burden was poorly predicted by observations obtained at the level of large geographical areas. CONCLUSIONS: The peak Flu-OR during the pandemic significantly exceeded a 15% critical threshold in almost half of the ICUs, with an uneven distribution with time, geographical areas and between University and non-University hospitals. An on-line assessment of Flu-OR via a simple dedicated registry may contribute to better match resources and needs. PMID- 22776233 TI - Fumarate hydratase inactivation in renal tumors: HIF1alpha, NRF2, and "cryptic targets" of transcription factors. AB - Biallelic inactivation of fumarate hydratase(FH) causes type 2 papillary renal cell carcinoma (PRCC2), uterine fibroids, and cutaneous leimyomas, a condition known as hereditary leiomyomatosis and renal cell cancer(HLRCC). The most direct effect of FH inactivation is intracellular fumarate accumulation. A majority of studies on FH inactivation over the past decade have focused on the theory that intracellular fumarate stabilizes hypoxia-inducible factor 1alpha(HIF1A) through competitive inhibition of HIF prolyl hydroxylases. Recently, a competing theory that intracellular fumarate activates nuclear factor (erythroid-derived 2)-like 2(NRF2) through post-translational modification of its negative regulator. Kelch like ECH-associated protein 1(KEAP1) has emerged from a computational modeling study and mouse model studies. This review dissects the origin of these two governing theories and highlights the presence of chromatin-structure-regulated targets of transcription factors, which we refer to as "cryptic targets" of transcription factors. One such cryptic target is heme oxygenase I(HMOX1), the expression of which is known to be modulated by the gene product of SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4, also known as BRG1). PMID- 22776234 TI - The genetics and biology of KRAS in lung cancer. AB - Mutational activation of KRAS is a common oncogenic event in lung cancer and other epithelial cancer types. Efforts to develop therapies that counteract the oncogenic effects of mutant KRAS have been largely unsuccessful, and cancers driven by mutant KRAS remain among the most refractory to available treatments. Studies undertaken over the past decades have produced a wealth of information regarding the clinical relevance of KRAS mutations in lung cancer. Mutant Kras driven mouse models of cancer, together with cellular and molecular studies, have provided a deeper appreciation for the complex functions of KRAS in tumorigenesis. However, a much more thorough understanding of these complexities is needed before clinically effective therapies targeting mutant KRAS-driven cancers can be achieved. PMID- 22776235 TI - Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients. AB - Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7Ralpha (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous, with the leukemic cell population differing from case to case. Through the comprehensive analysis of immunophenotypic patterns, the profiles of patient specific composite leukemia cell populations could provide detailed information helpful for the diagnosis, therapeutic monitoring, and individualized therapies for common ALL. PMID- 22776236 TI - Coupled action of gamma-glutamyl transpeptidase-glutathione and keratinase effectively degrades feather keratin and surrogate prion protein, Sup 35NM. AB - Recombinant Escherichia coli HB101 harboring keratinase rKP2 from Pseudomonas aeruginosa KS-1 degraded 2% chicken feather in LB-Amp medium in 24h. SEM analysis and detailed studies revealed that bacterial colonization of feather was a pre requisite for degradation of feather by keratinase. The mechanism of sulfitolysis revealed involvement of free cystinyl group as a source of redox during colonization as DTNB inhibited feather degradation by rKP2. Involvement of GGT GSH system in contribution of free cystinyl group for redox was established by using GGT knockout recombinant E. coli strain that failed to degrade feather inspite of successful colonization and keratinase production. Short term experiments further confirmed enhanced protein release from feather keratin in presence of GGT-GSH redox. In the presence of similar redox, rKP2 also degraded surrogate prion protein, Sup 35NM in 15 min at 37 degrees C, pH 7.0. PMID- 22776237 TI - Effective catalytic conversion of cellulose into high yields of methyl glucosides over sulfonated carbon based catalyst. AB - An amorphous carbon based catalyst was prepared by sulfonation of the bio-char obtained from fast pyrolysis (N(2) atm; ~ 550 degrees C) of biomass. The sulfonated carbon catalyst contained high acidity of 6.28 mmol/g as determined by temperature programmed desorption of ammonia of sulfonated carbon catalyst and exhibited high catalytic performance for the hydrolysis of cellulose. Amorphous carbon based catalyst containing -SO(3)H groups was successfully tested and the complete conversion of cellulose in methanol at moderate temperatures with high yields ca. >= 90% of alpha, beta-methyl glucosides in short reaction times was achieved. The methyl glucosides formed in methanol are more stable for further conversion than the products formed in water. The carbon catalyst was demonstrated to be stable for five cycles with slight loss in catalytic activity. The utilization of bio-char as a sulfonated carbon catalyst provides a green and efficient process for cellulose conversion. PMID- 22776239 TI - Privileged detection of conspecifics: evidence from inversion effects during continuous flash suppression. AB - The rapid visual detection of other people in our environment is an important first step in social cognition. Here we provide evidence for selective sensitivity of the human visual system to upright depictions of conspecifics. In a series of seven experiments, we assessed the impact of stimulus inversion on the detection of person silhouettes, headless bodies, faces and other objects from a wide range of animate and inanimate control categories. We used continuous flash suppression (CFS), a variant of binocular rivalry, to render stimuli invisible at the beginning of each trial and measured the time upright and inverted stimuli needed to overcome such interocular suppression. Inversion strongly interfered with access to awareness for human faces, headless human bodies, person silhouettes, and even highly variable body postures, while suppression durations for control objects were not (inanimate objects) or only mildly (animal faces and bodies) affected by inversion. Furthermore, inversion effects were eliminated when the normal body configuration was distorted. The absence of strong inversion effects in a binocular control condition not involving interocular suppression suggests that non-conscious mechanisms mediated the effect of inversion on body and face detection during CFS. These results indicate that perceptual mechanisms that govern access to visual awareness are highly sensitive to the presence of conspecifics. PMID- 22776238 TI - Guidelines for the management of hemophilia. AB - Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence-based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion-transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies. PMID- 22776240 TI - In situ electrostimulation drives a regenerative shift in the zone of infarcted myocardium. AB - Electrostimulation represents a well-known trophic factor for different tissues. In vitro electrostimulation of non-stem and stem cells induces myogenic predifferentiation and may be a powerful tool to generate cells with the capacity to respond to local areas of injury. We evaluated the effects of in vivo electrostimulation on infarcted myocardium using a miniaturized multiparameter implantable stimulator in rats. Parameters of electrostimulation were organized to avoid a direct driving or pacing of native heart rhythm. Electrical stimuli were delivered for 14 days across the scar site. In situ electrostimulation used as a cell-free, cytokine-free stimulation system, improved myocardial function, and increased angiogenesis through endothelial progenitor cell migration and production of vascular endothelial growth factor (VEGF). In situ electrostimulation represents a novel means to stimulate repair of the heart and other organs, as well as to precondition tissues for treatment with cell-based therapies. PMID- 22776242 TI - Special Issue: Short cervix and the risk of preterm birth. Introduction. PMID- 22776241 TI - Pulmonary tuberculosis diagnostic delays in Chad: a multicenter, hospital-based survey in Ndjamena and Moundou. AB - BACKGROUND: Tuberculosis remains one of the leading causes of morbidity and mortality in low-resource countries. One contagious patient can infect 10 to 20 contacts in these settings. Delays in diagnosing TB therefore contribute to the spread of the disease and sustain the epidemic. OBJECTIVES: The aim of this study was to assess delays in diagnosing tuberculosis and the factors associated with these delays in the public hospitals in Moundou and Ndjamena, Chad. METHODS: A structured questionnaire was administered to 286 new tuberculosis patients to evaluate patient delay (time from the onset of symptoms to the first formal or informal care), health-care system delay (time from the first health care to tuberculosis treatment) and total delay (sum of the patient and system delays). Logistic regression was used to identify risk factors associated with long diagnostic delays (defined as greater than the median). RESULTS AND DISCUSSION: The median [interquartile range] patient delay, system delay and total delay were 15 [7-30], 36 [19-65] and 57.5 [33-95] days, respectively. Low economic status (aOR [adjusted odds ratio] =2.38 [1.08-5.25]), not being referred to a health service (aOR = 1.75 [1.02- 3.02]) and a secondary level education (aOR = 0.33 [0.12-0.92]) were associated with a long patient delay. Risk factors for a long system delay were a low level of education (aOR = 4.71 [1.34-16.51]) and the belief that traditional medicine and informal care can cure TB (aOR = 5.46 [2.37 12.60]). CONCLUSION: Targeted strengthening of the health-care system, including improving patient access, addressing deficiencies in health-related human resources, and improving laboratory networks and linkages as well as community mobilization will make for better outcomes in tuberculosis diagnosis. PMID- 22776243 TI - Assessment of cervical length and the relationship between short cervix and preterm birth. AB - Premature effacement of the cervix, or short cervix, in the midtrimester of pregnancy currently represents the strongest predictor of spontaneous preterm birth. Numerous studies have examined the relationship between short cervix and preterm birth, and although differences in sensitivity and predictive value exist, the overwhelming consensus indicates that the risk of preterm birth increases with decreasing cervical length. Cutoff values for cervical length range from less than 25 mm to less than 15 mm depending on patient characteristics and gestational age. Importantly, short cervix is more sensitive for predicting earlier forms of prematurity (at <32 weeks) than later forms of prematurity (>32 weeks). Cervical length measured at 18 to 24 weeks' gestation appears to be the most valuable measurement. Cervical length assessments can be performed by digital examination, a cervical measurement device, transabdominal ultrasound, or transvaginal ultrasound. Transvaginal ultrasound is the most reliable method to evaluate cervical length, but it is not available in all locations. Current clinical practice standards do not recommend universal screening for cervical length; however, results of randomized controlled clinical trials provide evidence to support expanded screening programs by individual practitioners. PMID- 22776244 TI - Treatment options and recommendations to reduce preterm births in women with short cervix. AB - Premature shortening of the cervix, or short cervix, is the most predictive risk factor for preterm birth. Results of clinical studies of interventions to prevent preterm birth have shown that identifying at-risk women on the basis of cervical length versus obstetric history alone improves the likelihood of timely interventions with cervical cerclage or progesterone supplementation, improving outcomes. Debate continues over the use of cerclage; however, results of a meta analysis of randomized controlled trials provide evidence to support its use in women who have history of prior preterm birth and who develop short cervix before 24 weeks' gestation. Results of the recent PREGNANT trial, consistent with the earlier Fetal Medicine Foundation study, support the use of vaginal progesterone for prevention of preterm birth. In women identified by transvaginal ultrasound to have short cervix (10-20 mm) in midtrimester, daily vaginal progesterone gel reduced the risk of preterm birth before 33 weeks' gestation by 45% and before 28 weeks' gestation by 50%. Occurrence of any morbidity and mortality event also was significantly reduced by 43%, with a 61% reduction in the rate of respiratory distress syndrome in infants born to women receiving vaginal progesterone gel versus those receiving placebo. The safety profile of progesterone treatment in early pregnancy is well established, and studies of vaginal progesterone for prevention of preterm birth have identified no additional safety issues. Adverse events were comparable between women receiving progesterone and those receiving placebo. Recent guidelines issued by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recommend vaginal progesterone in women with no prior spontaneous preterm birth and cervical length of 20 mm or less at 24 weeks' gestation or earlier. Future studies will refine strategies for prevention of preterm birth to address other risk factors and determine the role of other interventions. PMID- 22776245 TI - Short cervix and the risk of preterm birth. PMID- 22776246 TI - The Aastrom experience. AB - Aastrom Biosciences has developed a proprietary cell-processing technology that enables the manufacture of ixmyelocel-T, a patient-specific multicellular therapy expanded from a small sample of a patient's own bone marrow. Ixmyelocel-T is produced under current good manufacturing practices (cGMP) in a fully closed, automated system that expands mesenchymal stem cells (MSCs) and macrophages. While the cell types in ixmyelocel-T are the same as those found in the bone marrow, the numbers of MSCs and alternative macrophages are greater in ixmyelocel T. We propose that the mixture of expanded MSCs and alternatively activated macrophages promote long-term tissue repair of ischemic tissue. The multiple cell types in ixmyelocel-T have a range of biological activities that are likely to contribute to a complex mechanism of action. Clinical trial data collected to date support the potential for ixmyelocel-T as an efficacious and safe treatment for ischemic cardiovascular indications, including critical limb ischemia (CLI) and a severe form of heart failure, dilated cardiomyopathy (DCM). The CLI clinical program has completed phase 2 and has reached concurrence with the Food and Drug Administration (FDA) on a phase 3 study (REVIVE) through the Special Protocol Assessment (SPA) process. The phase 3 study began screening patients in February 2012. The DCM clinical program will initiate phase 2b in 2012. PMID- 22776247 TI - Higher rate of colorectal cancer among patients with pyogenic liver abscess with Klebsiella pneumoniae than those without: an 11-year follow-up study. AB - AIM: Pyogenic liver abscess (PLA) has been reported as an early manifestation of colorectal cancer (CRC) in adults, but few studies have investigated this relationship. It is unclear if patients with Klebsiella pneumoniae PLA are at increased risk of subsequent CRC. Our aims were to estimate the incidence of CRC among patients with PLA and to compare the incidence of CRC between K. pneumoniae PLA and non-K. pneumoniae PLA groups. METHOD: We conducted a retrospective study of patients with PLA diagnosed between 2000 and 2009 at a medical centre in northern Taiwan. CRC status and survival status were determined until December 2010. Incidence data from the general population were retrieved from the Taiwan Cancer Registry. Outcome measures were defined as standardized incidence ratio and the incidence rate per 100,000 person-years. RESULTS: This study included 2294 patients, of whom 1194 (52%) had K. pneumoniae infection. During the follow up period, 54 (2.3%) patients were diagnosed with CRC, corresponding to an overall incidence rate of 669.1 (95% CI, 490.7-847.6) per 100,000 person-years. The adjusted hazard ratio of CRC was 2.68 times greater for patients with K. pneumoniae PLA than for those with non-K. pneumoniae PLA (95% CI, 1.40-5.11). CONCLUSION: Patients with K. pneumoniae PLA had a significantly higher rate of subsequent CRC than did patients with non-K. pneumoniae PLA. Colonoscopy is recommended to detect occult colonic malignancy in patients with PLA, particularly for patients over 60 years of age and with K. pneumoniae. PMID- 22776248 TI - Antioxidant sulforaphane and sensitizer trinitrobenzene sulfonate induce carboxylesterase-1 through a novel element transactivated by nuclear factor-E2 related factor-2. AB - Carboxylesterase-1 (CES1), the most versatile human carboxylesterase, plays critical roles in drug metabolism and lipid mobilization. This enzyme is highly induced by antioxidants and sensitizers in various cell lines. These compounds are known to activate nuclear factor-E2 related factor-2 (Nrf2) by reacting to kelch-like ECH-associated protein-1 (Keap1). The aims of this study were to determine whether antioxidant sulforaphane (SFN) and sensitizer trinitrobenzene sulfonate (TNBS) target Keap1 similarly and whether they use the same element for CES1 induction. Cells over-expressing Keap1 were treated with TNBS or SFN and the formation of disulfide bonds among Keap1 molecules were determined. SFN promoted intramolecular disulfide formation whereas TNBS promoted intermolecular disulfide formation of Keap1. Two elements, sensitizing/antioxidant response element (S/ARE) and ARE4, were identified to support Nrf2 in the regulated expression of CES1A1. Both elements were bound by Nrf2, however, the S/ARE element supported, whereas the ARE4 element repressed Nrf2 transactivation. The repression required higher amounts of Nrf2, suggesting that the transactivation through the S/ARE element dominates the trans-repression through the ARE4 element under normal antioxidative condition. These findings conclude that compounds, although triggering the Keap1-Nrf2 pathway, may differ in the mode of reacting with Keap1. These findings also conclude that both positive and negative Nrf2 elements exist even within the same gene, and such opposing mechanisms provide fine-tuning in transcriptional regulation by the Keap1-Nrf2 pathway. High levels of CES1 are linked to lipid retention. Excessive induction of CES1 by antioxidants and sensitizers likely provides a mechanism for potential detrimental effect on human health. PMID- 22776249 TI - A new complication of retained surgical gauze: development of malignant fibrous histiocytoma--report of a case with a literature review. AB - BACKGROUND: Primary visceral malignant fibrous histiocytoma (MFH) is a rare disease, and few cases have been reported in the English literature. However, retained foreign bodies in the abdomen after surgical procedures are important causes of intra-abdominal infections. For legal and ethical reasons, there are few publications in the literature. In this article, we describe for the first time a case of malign abdominal fibrous histiocytoma associated with a surgical sponge forgotten in the abdominal cavity a long time ago. CASE PRESENTATION: A 64 year-old male presented to our surgical department with cachexia, abdominal pain, distention and pyrexia of unknown origin. He had a medical history of abdominal surgery for peptic ulcer perforation 32 years ago. Clinical examination revealed fever with a distended and painful abdominal wall. Radiological imaging of the abdomen showed multiple heterogeneous masses in one large cystic cavityalmost completely filling the abdomen. The patient underwent a laparotomy, and interestingly, opening the cyst revealed retained surgical gauze (RSG). The origin of the tumor was the visceral peritoneum, and it was excised totally. CONCLUSIONS: Primary intra-abdominal MFH can present as a complication of long lasting RSG. Therefore, clinicians must remember this while establishing the differential diagnosis for patients with a history of previous abdominal surgery and presenting with symptoms associated with both the tumor and systemic inflammatory response. PMID- 22776250 TI - De novo transcriptome sequencing in a songbird, the dark-eyed junco (Junco hyemalis): genomic tools for an ecological model system. AB - BACKGROUND: Though genomic-level data are becoming widely available, many of the metazoan species sequenced are laboratory systems whose natural history is not well documented. In contrast, the wide array of species with very well characterized natural history have, until recently, lacked genomics tools. It is now possible to address significant evolutionary genomics questions by applying high-throughput sequencing to discover the majority of genes for ecologically tractable species, and by subsequently developing microarray platforms from which to investigate gene regulatory networks that function in natural systems. We used GS-FLX Titanium Sequencing (Roche/454-Sequencing) of two normalized libraries of pooled RNA samples to characterize a transcriptome of the dark-eyed junco (Junco hyemalis), a North American sparrow that is a classically studied species in the fields of photoperiodism, speciation, and hormone-mediated behavior. RESULTS: From a broad pool of RNA sampled from tissues throughout the body of a male and a female junco, we sequenced a total of 434 million nucleotides from 1.17 million reads that were assembled de novo into 31,379 putative transcripts representing 22,765 gene sets covering 35.8 million nucleotides with 12-fold average depth of coverage. Annotation of roughly half of the putative genes was accomplished using sequence similarity, and expression was confirmed for the majority with a preliminary microarray analysis. Of 716 core bilaterian genes, 646 (90 %) were recovered within our characterized gene set. Gene Ontology, orthoDB orthology groups, and KEGG Pathway annotation provide further functional information about the sequences, and 25,781 potential SNPs were identified. CONCLUSIONS: The extensive sequence information returned by this effort adds to the growing store of genomic data on diverse species. The extent of coverage and annotation achieved and confirmation of expression, show that transcriptome sequencing provides useful information for ecological model systems that have historically lacked genomic tools. The junco-specific microarray developed here is allowing investigations of gene expression responses to environmental and hormonal manipulations - extending the historic work on natural history and hormone mediated phenotypes in this system. PMID- 22776251 TI - New horizons for host defense peptides and lantibiotics. AB - Antimicrobial peptides from either microbial sources, or based on host defense peptides (HDPs) from higher organisms, show promising activity against human pathogens. Lantibiotics have been extensively engineered by either molecular biology approaches or chemistry and both natural and modified entities have been shown to have good efficacy in animal models of infection. Amongst HDPs either truncated peptides or non-peptide mimetic molecules show substantial promise both for their direct antibiotic action and also modulation of host functions. Members of both classes have reached clinical development for therapy of systemic infections and Clostridium difficile infection of the gastrointestinal tract. PMID- 22776252 TI - NF-kappaB signalling is attenuated by the E7 protein from cutaneous human papillomaviruses. AB - The high-risk Alpha-types of human papillomavirus (HPV) are the causative agent of cervical cancer, which is the second major cause of death among women worldwide. Recent investigations have shown that E7 from the Alpha-papillomavirus HPV-16 interacts with IKKalpha and IKKbeta of the IKK complex in the NF-kappaB pathway leading to an attenuation of the activity. There is a possible link between development of non-melanoma skin cancer and cutaneous Beta-papillomavirus but if these HPV types attenuate the NF-kappaB pathway is unclear. Seven different E7 proteins, representing four out of the five different species of the Beta genus (HPV-20, -37, -38, -92, -93 and -96) and one from the Gamma genus (HPV 4) were investigated for potential modulation of the NF-kappaB pathway in U2OS cells. Our results demonstrate that E7 from all the cutaneous HPV types were capable of inhibiting the NF-kappaB activity as well as E7 from HPV-16. In addition, E7 proteins from the cutaneous HPV types demonstrated interaction with IKKalpha but not with IKKbeta. The deregulation of the NF-kappaB pathway by cutaneous HPVs might contribute to the pathogenesis of non-melanoma skin cancers and its precursors. PMID- 22776253 TI - Improving bioavailability of phosphorous from cattle dung by using phosphatase immobilized on natural clay and nanoclay. AB - The high P retention of acidic Andisols makes necessary to increase our technological approaches in pasture management in the animal system production. Here, we evaluated the clay- or nanoclay-acid phosphatase complexes for improving phosphorus mineralization from degraded cattle dung. We implemented an immobilization mechanism of acid phosphatase (AP) using natural clays (allophanic and montmorillonite) and nanoclays as support materials. Also, we evaluated the mineralization of organic P containing in decomposed cattle dung with clay- and nanoclay-AP complexes by incubation studies. Clays and nanoclays were characterized by microscopy techniques as atomic force and confocal-laser scanning microscopy. We found that these support materials stabilized AP by encapsulation. Our results showed that immobilization on allophanic or montmorillonite materials improved both the specific activity (4-48%) and the V(max) (28-38%) of AP. Moreover, the enzyme had a better performance when immobilized on clay and nanoclay from Andisol than on montmorillonite materials. Phosphorous mineralization of cattle dung was regulated by water-soluble P present in the dung and P re-adsorption on allophanic materials. However, we were able to detect a potential capacity of AP immobilized on allophanic nanoclays as the best alternative for P mineralization. Further research with initially low water-soluble P containing organic materials is required to quantify the P mineralization potential and bioavailability of P from dung. PMID- 22776255 TI - Total arsenic and selenium analysis in Marcellus shale, high-salinity water, and hydrofracture flowback wastewater. AB - Trace levels of arsenic and selenium can be toxic to living organisms yet their quantitation in high ionic strength or high salinity aqueous media is difficult due to the matrix interferences which can either suppress or enhance the analyte signal. A modified thiol cotton fiber (TCF) method employing lower flow rates and centrifugation has been used to remove the analyte from complex aqueous media and minimize the matrix interferences. This method has been tested using a USGS (SGR 1b) certified reference shale. It has been used to analyze Marcellus shale samples following microwave digestion as well as spiked samples of high salinity water (HSW) and flow back wastewater (WRF6) obtained from an actual gas well drilling operation. Quantitation of arsenic and selenium is carried out by graphite furnace atomic spectroscopy (GFAAS). Extraction of arsenic and selenium from Marcellus shale exposed to HSW and WRF6 for varying lengths of time is also reported. PMID- 22776254 TI - Evaluation of methane oxidation activity in waste biocover soil during landfill stabilization. AB - Biocover soil has been demonstrated to have high CH(4) oxidation capacity and is considered as a good alternative cover material to mitigate CH(4) emission from landfills, yet the response of CH(4) oxidation activity of biocover soils to the variation of CH(4) loading during landfill stabilization is poorly understood. Compared with a landfill cover soil (LCS) collected from Hangzhou Tianziling landfill cell, the development of CH(4) oxidation activity of waste biocover soil (WBS) was investigated using simulated landfill systems in this study. Although a fluctuation of influent CH(4) flux occurred during landfill stabilization, the WBS covers showed a high CH(4) removal efficiency of 94-96% during the entire experiment. In the LCS covers, the CH(4) removal efficiencies varied with the fluctuation of CH(4) influent flux, even negative ones occurred due to the storage of CH(4) in the soil porosities after the high CH(4) influent flux of ~137 gm(-2) d(-1). The lower concentrations of O(2) and CH(4) as well as the higher concentration of CO(2) were observed in the WBS covers than those in the LCS covers. The highest CH(4) oxidation rates of the two types of soil covers both occurred in the bottom layer (20-30 cm). Compared to the LCS, the WBS showed higher CH(4) oxidation activity and methane monooxygenase activity over the course of the experiment. Overall, this study indicated the WBS worked well for the fluctuation of CH(4) influent flux during landfill stabilization. PMID- 22776256 TI - Use of thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) on identification of odorant emission focus by volatile organic compounds characterisation. AB - Volatile organic compounds (VOCs) from several different municipal solid wastes' treatment plants in Mallorca (Spain) have been analysed by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). Ambient (immission) air was collected during February and March 2011 by active sampling onto sorbents TenaxTM TA and CarboxenTM 1000. The study presents the chemical characterisation of 93 volatile organic compounds (VOCs) from an overall set of 84 immission air samples. 70 VOCs were positively identified. The linear fit for all 93 external standard calibration, from 10 mg L(-1) to 150 mg L(-1) (n=4), was within the range 0.97490% within 7 d. These results support the use of slow-release persulfate and ZVI candles as a means of treating BTEX compounds in contaminated groundwater. PMID- 22776258 TI - Effect of dissolved oxygen concentration (microaerobic and aerobic) on selective enrichment culture for bioaugmentation of acidic industrial wastewater. AB - The successful application of bioaugmentation is largely dependent on the selective enrichment of culture with regards to pH, temperature, salt, or specific toxic organic pollutants. In this study, we investigated the effect of dissolved oxygen (DO) concentrations (aerobic, >2 mg L(-1); microaerobic, <1 mg L(-1)) on yeast enrichment culture for bioaugmentation of acidic industrial wastewater (pH 3.9-4.7). Clone library analyses revealed that the yeast community shifted in response to different DO levels, and that Candida humilis and Candida pseudolambica were individually dominant in the aerobic and microaerobic enrichment cultures. This would significantly influence the isolation results, and further hinder bioaugmentation due to differences in DO environments during the enrichment and application periods. However, differences in the selective enrichment culture cannot be predicted based on differences in pollutant removal performance. Thus, DO concentrations (aerobic/microaerobic) should be considered a secondary selective pressure to achieve successful bioaugmentation. PMID- 22776259 TI - Biofuel production from crude palm oil with supercritical alcohols: comparative LCA studies. AB - A recent life cycle assessment (LCA) reported that biodiesel production in supercritical alcohols (SCA) produces a higher environmental load than the homogeneous catalytic process because an enormous amount of energy is required to recover excess alcohol. However, the excess alcohol could be dramatically reduced by increasing the operating temperature to 400 degrees C; although the product would have to be considered as an alternative biofuel instead of biodiesel. A comparative LCA of the biodiesel production in two SCA at 300 degrees C (C-SCA) and novel biofuel production in the same two SCA at 400 degrees C (N-SCA) is presented. It was clear that the N-SCA process produces a dramatically reduced environmental load over that of the C-SCA process due to a lower amount of excess alcohol being used. The N-SCA process could be improved in terms of its environmental impact by changing from fossil fuel to biomass-based fuels for the steam generation. PMID- 22776260 TI - Hydrothermal pretreatment of microalgae for production of pyrolytic bio-oil with a low nitrogen content. AB - Microalgae can be converted to an energy-dense bio-oil via pyrolysis; however, the relatively high nitrogen content of this bio-oil presents a challenge for its direct use as fuels. Therefore, hydrothermal pretreatment was employed to reduce the N content in Nannochloropsis oculata feedstock by removing proteins without requiring significant energy inputs. The effects of reaction conditions on the yield and composition of pretreated algae were investigated by varying the temperature (150-225 degrees C) and reaction time (10-60 min). Compared with untreated algae, pretreated samples had higher carbon contents and enhanced heating values under all reaction conditions and 6-42% lower N contents at 200 225 degrees C for 30-60 min. The pyrolytic bio-oil from pretreated algae contained less N-containing compounds than that from untreated samples and the bio-oil contained mainly (44.9% GC-MS peak area) long-chain fatty acids (C14-C18) which can be more readily converted into hydrocarbon fuels in the presence of simple catalysts. PMID- 22776261 TI - Process optimization for microwave-assisted direct liquefaction of Sargassum polycystum C.Agardh using response surface methodology. AB - Response surface methodology (RSM) was used to optimize the microwave-assisted direct liquefaction of Sargassum polycystum C.Agardh in ethylene glycol (EG) with H(2)SO(4) as a catalyst. Based on the results of single factor experiments, EG-to feedstock ratio, temperature and catalyst content were chosen as independent variables for a central composite rotatable design (CCRD). The optimal liquefaction conditions were estimated as: the EG-to-feedstock ratio of 18.50:1 (w/w), the temperature of 170 degrees C, the reaction time of 15 min, catalyst content of 9.6% (catalyst/EG, w/w%) and microwave power of 400 W with the liquefaction yield of 87.70%. The bio-oils were mainly composed of fatty acid methyl ester and alkane with a long chain from C(17) to C(20). PMID- 22776262 TI - Effect of fermented wastewaters from butter production on phosphates removal in a sequencing batch reactor. AB - This study determined the potential for fermented wastewaters from butter production plant to act as a carbon source to facilitate phosphates removal. Synthetic dairy wastewaters were treated using SBR, with doses of fermented wastewaters. An increase in the fermented wastewater doses were found to improve the effluent quality in respect of phosphates and nitrates. The lowest concentrations of phosphate and nitrates, respectively 0.10 +/- 0.04 mg PO(4)-PL( 1) and 1.03 +/- 0.22 mg NO(3)-NL(-1), were noted in the effluent from the reactor fed with fermented wastewaters in a dose of 0.25 L d(-1) per 0.45 L d(-1) of wastewaters fed to the reactor. In the case of the two highest doses, an increase in effluent COD was stated. The higher effectiveness resulted from the fact that the introduction of fermented wastewaters caused an increase in the easily available carbon compounds content and the predominance of acetic acid amongst VFAs available to dephosphatating and denitrifying bacteria. PMID- 22776263 TI - Stimulation of bone formation in the expanding premaxillary suture with a GSK 3beta inhibitor. AB - OBJECTIVES: Glycogen synthase kinase-3beta (GSK-3beta)/beta-catenin signaling mediates osteogenesis in response to mechanical loading. We tested the hypothesis that local administration of a GSK-3beta inhibitor could stimulate new bone formation in the expanding premaxillary suture. MATERIALS AND METHODS: Thirty five Sprague-Dawley rats were subjected to premaxillary suture expansion using a helix spring. The experimental rats were given one or two local injections of SB 415286, a small-molecule GSK-3beta inhibitor. Animals were administered calcein and sacrificed on day 7 to quantify new bone formation. To evaluate the proliferation and differentiation of osteoblasts, rats were labeled with bromodeoxyuridine on day 1 and sacrificed on day 2 or 4. beta-catenin expression was evaluated by immunohistochemical staining. RESULTS: Two injections of SB 415286 led to an elevation of beta-catenin expression and an increase in the number of proliferating osteoblasts in expanding sutures on day 2 and day 4. Consequently, new bone formation in the suture increased significantly on day 7. CONCLUSIONS: These results suggest that local delivery of a GSK-3beta inhibitor could stimulate bone formation in the expanding premaxillary suture by eliciting beta-catenin signaling. GSK-3beta could be a pharmaceutical target for improving the effect of orthodontic treatments such as rapid palatal expansion. PMID- 22776264 TI - The measurement of relative efficiency of general practice and the implications for policy makers. AB - PURPOSE: This study aimed to compare technical efficiency of general practice (GP) delivered by the twenty Regions of Italy's decentralized healthcare system and to determine if it was affected by contextual factors. METHODS: First, we calculated the Regional efficiency scores by means of Data Envelopment Analysis. Then we carried out a regression analysis to investigate the influence of contextual factors on the efficiency in the provision of GP services. RESULTS: Six Northern Regions were identified as efficient using the best combinations of general practitioners to deliver a given level of GP outcomes. Compared with peer benchmarks, inefficient Regions used more (on-call and regular) general practitioners with important underproductions of outputs (e.g. avoidable hospitalizations). The regression analysis showed a negative relationship between efficiency and the Regional total health care expenditures as percentage of its Gross Domestic Product. DISCUSSION: Improving efficiency of GP services delivery is likely to result in reduced health expenditures. Since there is a general tendency in Europe to decentralize governmental systems of countries and Italy can be seen as an extreme example of this trend, we consider our findings of high relevance for international comparative studies on performance of primary care systems. PMID- 22776265 TI - Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. AB - Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA H19 is up-regulated in hypoxic stress and in some tumors. However, the contributions of H19 to gastric cancer remain largely unknown. In this study, we assayed the H19 expression level in gastric cancer tissues by real-time PCR, and defined the biological functions by flow cytometry and RNA immunoprecipitation. We demonstrated that H19 levels were markedly increased in gastric cancer cells and gastric cancer tissues compared with normal controls. Moreover, ectopic expression of H19 increased cell proliferation, whereas H19 siRNA treatment contributed to cell apoptosis in AGS cell line. We further verified that H19 was associated with p53, and that this association resulted in partial p53 inactivation. These data suggest an important role for H19 in the molecular etiology of gastric cancer and potential application of H19 in gastric cancer therapy. PMID- 22776266 TI - Activity-based fluorescent probes for monitoring sulfatase activity. AB - A small-molecule probe for sulfatase is developed that shows a significant change in fluorescence upon reaction with sulfatase in an activity-based manner. As this probe is free from interference from background fluorescence caused by an unreacted probe, it could be a simple and efficient tool for the study of sulfatase activity. PMID- 22776267 TI - Central vein stenosis in a dialysis patient: a case report. AB - INTRODUCTION: Central vein stenosis is not a rare problem in patients on dialysis. Placement of a central vein catheter for dialysis access substantially increases the risk of central vein stenosis. However, even in patients without a previous history of central vein catheter placement, a stenosis can be found in up to 40% of patients. CASE PRESENTATION: We report the case of a 60-year-old male Caucasian German dialysis patient who complained of dry cough, swelling of his right arm and facial edema. Computed tomography venography showed a near total stenosis of his brachiocephalic vein. We discuss the incidence and risk of central vein stenosis in patients on dialysis and report on a successful minimally invasive interventional treatment. CONCLUSION: Central vein stenosis is not a rare problem in patients on hemodialysis and can even occur without previous placement of central venous catheters. High shunt volumes seem to increase the risk associated with central vein catheters. PMID- 22776269 TI - Effect of penguin and seal excrement on mercury distribution in sediments from the Ross Sea region, East Antarctica. AB - Total mercury (Hg) concentration and several other geochemical parameters were determined for five sediment profiles from the Antarctic Ross Sea region. Our data exhibit significant positive correlations between Hg concentration and total organic carbon (TOC) content in all profiles, suggesting the predominant role of organic matter (OM) as a Hg carrier. The OM in the sediments originates primarily from penguin guano and algae. High Hg content in guano and a positive correlation between Hg and a guano bio-element (phosphorus, P) in the ornithogenic sediment profiles (MB6, BI and CC) indicate that Hg was strongly influenced by guano input. The bottom sediments of MB6 with seal hairs contain relatively high Hg. This increase is attributed to the input of seal excrement, suggesting that sedimentary Hg may be an effective trophic-level indicator from seals to penguins. The enrichment factor (EF) for Hg was calculated and the results indicated apparent Hg enrichment in the sediment profiles from the Ross Sea region caused by bio-vectors such as penguins and seals. Compared with typical sediments from other sites in Antarctica and the SQGs (sediment quality guidelines), the total amount of Hg in our study area is still not considered to be adversely high. PMID- 22776271 TI - Laparoscopic total mesorectal excision: early and late results. AB - BACKGROUND: Laparoscopic colectomy is superior to open colectomy in terms of short-term surgical outcomes. There is solid evidence indicating that laparoscopic and open surgery are equally effective for colon cancer, but for rectal cancer, the issues of neoadjuvant treatment, the need for total mesorectal excision and autonomic nerve preservation, and the technical demands of a well constructed low colorectal or coloanal anastomosis challenge even the most specialized surgeons. This review discusses the available evidence on short-term and long-term outcomes after laparoscopic total mesorectal excision for rectal cancer. DATA SOURCES: Systematic MEDLINE and Embase searches of outcomes on laparoscopic total mesorectal excision were conducted and data were retrieved. CONCLUSIONS: Information on short-term and long-term outcomes after laparoscopic total mesorectal excision remains limited. Data are mainly retrospective and from randomized studies based on few cases that had minimal follow-up. Early non oncologic surgical outcomes seem improved after laparoscopy, but an increased rate of positive circumferential resection margins has been detected. Though scarce, the available evidence on recurrence and survival does not indicates disadvantages to the laparoscopic approach. PMID- 22776270 TI - Results of a questionnaire on the treatment of patients with Behcet's syndrome: a trend for more intensive treatment. AB - OBJECTIVES: To determine the preferred treatment for patients with Behcet's syndrome. METHODS: A questionnaire was given to all participants of the 2010 meeting of the International Society for Behcet's Disease. RESULTS: Forty-one respondents from 6 different subspecialties. In the case of a patient with (severe) posterior uveitis or parenchymal central nervous system (CNS) disease no consensus was seen. A diffuse spectrum of different schedules were given. In both uveitis and CNS disease the majority of respondents preferred treatment options consisting of combination systemic therapy and systemic corticosteroids. TNF was preferred as first line drug in uveitis in 7.5% and in severe uveitis in 32.5% of respondents. In parenchymal CNS disease TNF blockage was given by 17% of the respondents. EULAR guidelines regarding uveitis were followed by 12/40 physicians. In patients with a new deep vein thrombosis, 90% of respondents would intensify immunosuppression. More than half would also anticoagulate. CONCLUSIONS: Although consensus about how to treat patients with Behcet syndrome in different clinical situations is far from present, treatment has become more intensive when compared to 10-20 years ago. More uniformity should be sought for in the decision process in individual patients with Behcet's syndrome, regarding their treatment, as well as adhering to evidence, as presented in the EULAR guidelines, when present. PMID- 22776268 TI - Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications. AB - Fatigue is one of the most common and distressing side effects of cancer and its treatment, and may persist for years after treatment completion in otherwise healthy survivors. Guided by basic research on neuro-immune interactions, a growing body of research has examined the hypothesis that cancer-related fatigue is driven by activation of the pro-inflammatory cytokine network. In this review, we examine the current state of the evidence linking inflammation and cancer related fatigue, drawing from recent human research and from experimental animal models probing effects of cancer and cancer treatment on inflammation and fatigue. In addition, we consider two key questions that are currently driving research in this area: what are the neural mechanisms of fatigue, and what are the biological and psychological factors that influence the onset and/or persistence of inflammation and fatigue in cancer patients and survivors? Identification of the mechanisms driving cancer-related fatigue and associated risk factors will facilitate the development of targeted interventions for vulnerable patients. PMID- 22776273 TI - The Endoscopic Surgical Skill Qualification System for gastric surgery in Japan. AB - INTRODUCTION: Laparoscopic surgery has been increasing in popularity in recent years. In 2004, the Japan Society for Endoscopic Surgery developed its Endoscopic Surgical Skill Qualification System (ESSQS) to assess surgeons. METHODS: To earn the ESSQS accreditation, applicants must submit an unedited operative video in which they perform either a distal gastrectomy or pylorus-preserving gastrectomy with lymph node dissection for gastric cancer. The videos are assessed by two separate judges based on detailed criteria for common and procedure-specific technical-grade slips. Common criteria from all fields of gastrointestinal and general surgery are used to evaluate the basic laparoscopic surgical skills and autonomy of the operator. The target organ determines the procedure-specific criteria are set to assess whether or not adequate oncological clearance has been achieved. RESULTS: Between 2004 and 2009, 154 (44.6%) out of 345 applicant surgeons assessed under the ESSQS for gastric surgery have been accredited. Interrater agreement was acceptable and ranged between 0.21 and 0.59. CONCLUSION: The ESSQS system may facilitate improvement in surgical technique and the standardization of laparoscopic surgery in Japan. PMID- 22776272 TI - Endoscopy-assisted anastomosis: a modified technique for laparoscopic side-to side esophagojejunostomy following a total gastrectomy. AB - INTRODUCTION: Esophagojejunostomy with a circular stapling device is sometimes difficult to perform in a laparoscopic setting. On the other hand, a side-to-side anastomosis with a linear stapling device is technically challenging. METHODS: Between June 2002 and March 2008, 10 consecutive patients underwent a laparoscopy assisted total gastrectomy using a side-to-side anastomosis technique. Of these patients, four underwent a laparoscopy-assisted total gastrectomy with a modified anastomosis technique. A small wound was created on the antimesenteric side of the jejunum 5 cm distal to the resected portion and then in the lower esophagus. A peroral endoscope was advanced to the hole, and the cartridge fork was introduced into the lower esophagus under endoscopic guidance. The device (45 mm, blue) was fired to create an antiperistaltic side-to-side anastomosis. The common entry hole was closed by transecting the jejunum and the esophagus with another linear stapler and by using an endoscope as a stent. RESULTS: Four patients underwent the modified procedure and did not require an open procedure. One patient developed a pancreatic fistula, which was treated conservatively. The average operative time, reconstruction time and blood loss were 483 +/- 133 minutes, 139 +/- 31 minutes, and 199 +/- 121 mL, respectively. An introduction of the stapler into the lower esophagus and a closure of the common entry hole were performed safely without any stress. CONCLUSION: Although several techniques must be compared to determine the ideal procedure for laparoscopic esophagojejunostomy, the modified side-to-side anastomosis technique may be useful in clinical settings. PMID- 22776274 TI - Appendiceal stump closure in children with complicated appendicitis: a prospective analysis of endoloops versus endostaples. AB - INTRODUCTION: Laparoscopic appendectomy (LA) can be performed safely and effectively using endoloops (EL) or endostaples (ES). We compared EL and ES for stump closure during LA for complicated appendicitis in children. METHODS: All LA for complicated appendicitis performed between July 2005 and August 2009 were assessed prospectively. EL were used in 37 procedures and ES in 31. Apart from choice of technique which was the personal preference of the attending surgeon, all patients were managed according to the same intraoperative and postoperative protocols. RESULTS: There was no significant difference between mean age at operation; gender ratio; mean preoperative and postoperative white blood cell; mean preoperative and postoperative white blood cell C-reactive protein; histopathology; mean operating time (EL: 71 minutes; ES: 64 minutes); mean hospitalization (EL: 5.3 days; ES: 5.1 days); febrile period (EL: 2.1 days; ES: 1.9 days); white blood cell normalization (EL: 2.6 days; ES: 2.4 days); and intravenous antibiotic usage (EL: 3.8 days; ES: 3.7 days). There were no intraoperative complications or ICU admissions in either group, but two EL cases required conversion to open surgery (P=NS). Incidences of intra-abdominal abscess (EL: n=1 or 2.7%; ES: n=1 or 3.2%), transient ileus (EL: n=2 or 5.4%; ES: n=2 or 6.4%), small bowel obstruction (EL: n=0; ES: n=0), and wound infection (EL: n=1 or 2.7%; ES: n=1 or 3.2 %) were not significantly different. Rate of rehospitalization for EL was 2.7% (n=1; colitis), and for ES, it was 3.2% (n=1; intra-abdominal abscess) (P=NS). Mean cost for EL was US$890, and for ES, it was US$1300. CONCLUSION: This is the first prospective study comparing EL and ES during LA for complicated appendicitis in children. ES is more expensive, but there was no significant difference in morbidity for this technique, particularly with regard to incidence of postoperative intra-abdominal abscess. PMID- 22776275 TI - Single-port versus needlescopic versus conventional laparoscopic cholecystectomy: a comparative study. AB - INTRODUCTION: Single-port laparoscopic cholecystectomy (LC) has been recently introduced to achieve clinical benefits over standard LC. However, surgical outcomes of this operation have been poorly described compared with current techniques. The purpose of this study is to evaluate the surgical outcomes of single-port LC compared with needlescopic and conventional LC. METHODS: We reviewed the surgical outcomes of consecutive patients with symptomatic gallbladder stone disease who underwent single-port LC (31 cases), needlescopic LC (26 cases) and conventional LC (32 cases) from March 2009 to January 2010. Operation time, hospital stay, conversion, complications, and postoperative pain using visual analog scale were analyzed. In addition, patients were interviewed for overall satisfaction and cosmetic results. RESULTS: BMI in the single-port group was significantly lower than in the conventional group (26.0 +/- 4.0 vs 30.8 +/- 7.3 kg/m(2) , P=0.0017). Operation time in the single-port group was significantly longer than in the conventional group (65.1 +/- 20.1 minutes vs 52.2 +/- 19.6 minutes, P=0.012). There was one conversion in the single-port group. In nine cases in the single-port group (29%), a Kirschner wire or a suture retractor helped visualization. There was one complication in the single-port group (wound infection) and one in the needlescopic group (bile leak, requiring laparoscopy). Hospital stay, visual analog scale scores, and overall satisfaction did not vary among these groups. Greater cosmetic satisfaction was shown in the single-port group compared with the conventional group (P=0.039). CONCLUSION: Single-port LC is feasible and secure, with better cosmetic results than conventional LC. Further prospective randomized studies are still required to show its superiority over current LC techniques. PMID- 22776276 TI - Implementation and learning of laproscopic donor nephrectomy by a non-transplant general surgeon with advanced laparoscopic skills. AB - INTRODUCTION: Traditionally performed by vascular surgeons or urologists, laparoscopic nephrectomy for live kidney donor transplantation has emerged as a new effective and safe technique. This study examines the implementation of this technique at our centre, as performed by a single general surgeon with expertise in advanced laparoscopic surgery. METHODS: Patient records for 78 live donor transplants performed between February 2002 and September 2008 were divided into two groups (with 39 patients each) analyzed. A variety of outcome variables were compared. The same individual surgeon performed all laparoscopic donor nephrectomy (LDN) procedures. RESULTS: A significant advantage was noted for LDN with respect to hospital stay (LDN 5.1 +/- 1.1 days vs open donor nephrectomy [ODN] 6.4 +/- 2.6 days, P=0.01) while ODN had a significant advantage with respect to operative time (LDN 241.1 +/- 55.7 min vs ODN 152.0 +/- 27.7 min, P<0.01). Within the LDN group, we noted a significant shortening in the operation time with each case as experience increased (see graph; P<0.01). The total postoperative complication rate was similar in both groups (LDN: 31% vs ODN: 44%, P=0.25). There was a trend towards more respiratory complications in ODN (ODN 11/39 [28%] vs LDN 5/39 [13%], P=0.09). CONCLUSION: While implementing a new procedure may result in longer operative times initially, these improve with time, and our data demonstrates no compromise in patient safety or outcomes. The LDN procedure proved to be a desirable alternative to ODN, with shorter hospital stay and improved operator skills with each case, and without significant compromise in allograft recovery. PMID- 22776277 TI - Gasless laparoscopically assisted myomectomy using a wound retraction system. AB - INTRODUCTION: The purpose of this study was to elucidate the feasibility of gasless laparoscopically assisted myomectomy (LAM) using a wound retraction system. This method treats symptomatic uterine myomas by combining laparoscopy with a mini-laparotomy to enucleate myoma nodules and to close the uterine myometrium. METHODS: This study includes 275 patients who underwent gasless LAM. For patients with fewer than three myoma nodules, the location of the largest nodule was classified as anterior, fundal, or posterior. The operative outcomes, intraoperative and postoperative courses, and complications were examined. RESULTS: All operations were performed satisfactorily, and no conversions to laparotomy were required. None of the patients developed serious complications. The mean blood loss and operating time were 190.3 mL and 152.2 minutes, respectively. The mean myoma size was 8.9 cm, and the mean number of myomas per patient was 2.8. The average postoperative hospital stay was 5.7 days. There were no significant differences in resected myoma size, blood loss, and surgical duration with respect to the location of the largest nodule. CONCLUSION: Gasless LAM with a wound retractor is feasible and allows surgeons to perform myomectomy safely and cost-effectively, without requiring advanced laparoscopic surgical skills and while maintaining minimum invasiveness. PMID- 22776278 TI - Results of a national survey on laparoscopic bariatric surgery in Japan, 2000 2009. AB - INTRODUCTION: In Japan, laparoscopic bariatric surgery has not been popular until recently because morbidly obese patients were infrequently encountered previous and Japanese health insurance does not cover this type of surgery. In 2010, the Japan Research Society for Endoscopic and Laparoscopic Treatments of Obesity undertook the first nationwide survey on laparoscopic bariatric surgery to evaluate its current status and outcomes. METHODS: A mail survey was sent to the society's 64 member institutions, which included almost all institutions in Japan actively performing laparoscopic gastrointestinal surgery. RESULTS: From 2000 to 2009, 340 laparoscopic bariatric procedures, in total, were performed in nine of the 64 institutions (14%). The most popular procedure was laparoscopic Roux-en-Y gastric bypass (LRYGB, n=147), second was laparoscopic sleeve gastrectomy (LSG, n=102), and third was laparoscopic adjustable gastric banding (LAGB, n=55). However, the number of LRYGB procedures has decreased while the number of LSG procedures has rapidly increased. Total morbidity rates were 12.2% for LRYGB, 10.9% for LAGB, and 7.8% for LSG. Percent excess weight loss was 78% at 5 years after LRYGB, 52% at 4 years after LAGB, and 68% at 2 years after LSG. Although the bariatric procedures frequently resolved or improved obesity-related comorbidities, LRYGB appears to be superior to LAGB, as was previously reported. CONCLUSION: The first nationwide survey of laparoscopic bariatric surgery in Japan clearly showed the current status and outcomes of this group of procedures. The Japanese results appear to be comparable to similarly undertaken surveys in Europe and the USA. PMID- 22776279 TI - Pure laparoscopic hepatectomy for hepatocellular carcinoma patients with severe liver cirrhosis. AB - Hepatocellular carcinoma often arises in cirrhotic livers. Patients with severe liver cirrhosis who undergo hepatectomy often develop postoperative liver failure, even if the hepatectomy is limited. Here, we report six patients with severe liver cirrhosis (Child-Pugh B/C and indocyanine green retention rate at 15 min >= 40%) who underwent pure laparoscopic hepatectomy. Their perioperative course was favorable and comparable to that of other hepatocellular carcinoma patients with mild-moderate liver cirrhosis. In patients with severe liver cirrhosis, pure laparoscopic hepatectomy minimizes the disturbance in collateral blood and lymphatic flow caused by laparotomy and liver mobilization, as well as the mesenchymal injury caused by compression of the liver. It limits complications such as massive ascites, which can lead to severe postoperative liver failure. Good candidates for the procedure include patients with severe liver cirrhosis who have tumors on the liver surface and in whom adaptation to ablation therapy is difficult and/or who experience local recurrence after repeat treatments. PMID- 22776280 TI - Intrapulmonary schwannoma in the right middle lobe: a case report. AB - Herein, we report a patient with a rare disease, intrapulmonary schwannoma. The patient was a 61-year-old woman who had a 20 mm * 18 mm nodule, with a clear boundary and homogeneous content, on the central side of S4 in the right lung on chest CT. On PET with 18- fluorodeoxyglucose scanning, 18-fluorodeoxyglucose accumulations with a maximal standardized uptake value of 2.5 and 3.3 were observed in the early and late phases, respectively, suggesting a malignant tumor. A thoracoscopic right middle lobectomy was performed because the tumor was present in the segmental bronchial region of the middle lobe. Intrapulmonary schwannoma accounts for 0.2% of lung tumor cases, and cases involving patients who have undergone preoperative PET with 18- fluorodeoxyglucose scanning have rarely been reported. PMID- 22776281 TI - Novel technique for total laparoscopic myomectomy: the "bottom-up suture". AB - INTRODUCTION: As more women with symptomatic uterine myomas undergo laparoscopic management without hysterectomy, we increasingly encounter many difficult situations, such as of the need to extract large intramural myomas. Even for a skilled surgeon, laparoscopic myomectomy in such a situation is difficult. We have established a new technique for laparoscopic myomectomy to solve these issues called the "bottom-up suture" method. MATERIALS AND SURGICAL TECHNIQUE: Before complete removal of the myoma, countertraction is applied by an assistant with a claw forceps, elevating the bed of the myoma to make suturing easy. The deep myometrium can be sutured while the myoma is still attached to the uterus. DISCUSSION: This technique, the "bottom-up suture," may improve the suturing of laparoscopic myomectomies. The advantages of this technique are that it is easy to control unexpected bleeding, and dead space formation can be prevented even when the myomas have grown deep into the uterine myometrium. This technique will become a reliable standard for laparoscopic myomectomy. PMID- 22776282 TI - Video-assisted neck surgery for thyroid tumor: gasless lateral approach. AB - A 27-year-old woman with a thyroid tumor underwent right hemithyroidectomy to rule out malignancies such as follicular carcinoma of thyroid. A subplatysmal skin flap was dissected after making an incision in the anterior aspect of the neck, and the thyroid gland was exposed through the avascular space between the heads of the sternocleidomastoid muscle. After the insertion of the original retractor, video-assisted hemithyroidectomy was performed using ultrasonic surgical devices and conventional endoscopic forceps. Pathological examination of the resected specimen revealed follicular adenoma, and the postoperative course was uneventful. A lateral gasless approach for video-assisted thyroidectomy enables visualization of an adequate operative field and appears to be a safe and effective method. PMID- 22776283 TI - Cross-cultural adaptation to the Dutch language of the PainDETECT-Questionnaire. AB - BACKGROUND: The PainDETECT-Questionnaire (PDQ) helps to identify neuropathic components in patients suffering from pain. It can be used by clinicians in daily practice and in clinical trials. AIM: The aim of this study is to perform a translation and cross-cultural adaptation of the PDQ for use in the Netherlands and Belgium. METHODS: The first phase was to translate and cross-culturally adapt the PDQ to Dutch. The second phase was to assess the face validity in the Netherlands and Belgium using qualitative and quantitative data collection. RESULTS: The length, the readability, and the clarity of the questionnaire were good for all patients. The questionnaire was judged to have a good layout and to be clearly organized. CONCLUSION: The PDQ Dutch language Version is a well translated and cross-culturally adapted questionnaire, which might be useful for screening for neuropathic components of pain in the Netherlands and Belgium. PMID- 22776284 TI - Evaluation of a patient-initiated review system in rheumatoid arthritis: an implementation trial protocol. AB - BACKGROUND: Rheumatoid arthritis is a chronic inflammatory condition that affects the joints causing unpredictable episodes of pain, stiffness and disability. People with rheumatoid arthritis usually require lifelong specialist follow-up but frequently have periods when their disease can be managed through self-care or that provided by their general practitioner. Compared to the traditional clinician-driven care in rheumatoid arthritis, patient-initiated care has proven to be more beneficial in terms of reducing unnecessary medical reviews, providing greater satisfaction to patients and staffs and maintaining the patient's physical and psychological status. We aim to evaluate the implementation of a patient-initiated review system in a routine secondary care rheumatology service in a public hospital in England, where patients get the opportunity to self manage their disease by requesting specialist reviews at times of need instead of clinician-scheduled appointments. METHODS/DESIGN: Three hundred and eighty patients attending routine review at Plymouth Hospitals NHS Trust will be randomised to either enrol immediately into a patient-initiated review system (direct access group), or to be seen regularly by a clinician at the hospital (regular clinician-initiated group). Patients (or their general practitioner) in the direct access group can arrange a review by calling a rheumatology nurse-led advice line that enables telephone delivered clinical advice, or where appropriate, an appointment with a rheumatologist within 10 working days. Patients in the regular clinician-initiated group will attend their planned appointments at regular intervals during the intervening period of 12 months. The primary outcome of interest is patient satisfaction; secondary outcomes include service use, waiting times and clinical measures. Semi-structured, in-depth interviews will be conducted with a subset of patients and staff with the aim of identifying facilitators/barriers in implementing patient-initiated clinics. DISCUSSION: The implementation of a patient-initiated review system in routine care rheumatology will replace the fixed clinician-driven review system with a more flexible patient-driven system where patients usually self-manage their disease, but can request prompt help when required. We believe that this study will enable a comparison of the changes in local services and will be helpful in exploring the benefits/drawbacks of such implementation, thus providing lessons for implementation in other hospitals and for other chronic diseases. PMID- 22776286 TI - Stem cells and regenerative medicine. AB - The remarkable speed with which the field of stem cell biology has evolved is unprecedented and has already changed the way we do science. In this series of articles we have invited leading experts to present their efforts in moving from the bench to the bedside, with the hope that we can learn from the experiences of the pioneers. PMID- 22776285 TI - Prognostic impact of fecal pH in critically ill patients. AB - INTRODUCTION: We have reported that altered gut flora is associated with septic complications and eventual death in critically ill patients with systemic inflammatory response syndrome. It is unclear how fecal pH affects these patients. We sought to determine whether fecal pH can be used as an assessment tool for the clinical course of critically ill patients. METHODS: Four hundred ninety-one fecal samples were collected from 138 patients who were admitted to the Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Japan. These patients were treated in the intensive care unit for more than 2 days. Fecal pH, fecal organic acids, and fecal bacteria counts were measured and compared by survived group and nonsurvived group, or nonbacteremia group and bacteremia group. Logistic regression was used to estimate relations between fecal pH, age, sex, or APACHE II score and mortality, and incidence of bacteremia. Differences in fecal organic acids or fecal bacteria counts among acidic, neutral, and alkaline feces were analyzed. RESULTS: The increase of fecal pH 6.6 was significantly associated with the increased mortality (odds ratio, 2.46; 95% confidence interval, 1.25 to 4.82) or incidence of bacteremia (3.25; 1.67 to 6.30). Total organic acid was increased in acidic feces and decreased in alkaline feces. Lactic acid, succinic acid, and formic acid were the main contributors to acidity in acidic feces. In alkaline feces, acetic acid was significantly decreased. Propionic acid was markedly decreased in both acidic and alkaline feces compared with neutral feces. No differences were noted among the groups in bacterial counts. CONCLUSIONS: The data presented here demonstrate that the fecal pH range that extended beyond the normal range was associated with the clinical course and prognosis of critically ill patients. PMID- 22776287 TI - Teratocarcinoma formation in embryonic stem cell-derived neural progenitor hippocampal transplants. AB - Embryonic stem cells (ESCs) hold great therapeutic potential due to their ability to differentiate into cells of the three primary germ layers, which can be used to repopulate disease-damaged tissues. In fact, two cell therapies using ESC derivatives are currently in phase I clinical trials. A main concern in using ESCs and their derivatives for cell transplantation is the ability of undifferentiated ESCs to generate tumors in the host. Positive selection steps are often included in protocols designed to generate particular cell types from ESCs; however, the transition from ESC to progenitor cell or terminally differentiated cell is not synchronous, and residual undifferentiated cells often remain. In our transplants of ESC-derived neural progenitors (ESNPs) into the adult mouse hippocampus, we have observed the formation of teratocarcinomas. We set out to reduce teratocarcinoma formation by enrichment of ESNPs using fluorescence-activated cell sorting (FACS) and have found that, although enrichment prior to transplant reduces the overall rate of teratocarcinoma formation, the tumorigenicity of cell batches can vary widely, even after FACS enrichment to as much as 95% ESNPs. Our data suggest that this variability may be due to the percentage of residual ESCs remaining in the transplant cell population and to the presence of pluripotent epiblast-like cells, not previously identified in transplant batches. Our data emphasize the need for stringent characterization of transplant cell populations that will be used for cell replacement therapies in order to reduce the risk of tumor formation. PMID- 22776288 TI - Single-incision right hemicolectomy for malignancy: a feasible technique with standard laparoscopic instrumentation. AB - AIM: Single-incision laparoscopy is a rapidly evolving technique in the spectrum 'standard laparoscopy-natural orifice transluminal endoscopic surgery (NOTES)'. From a commercial perspective, purchase of articulating instruments is advised. However, here we present our early experience with single-incision laparoscopy for right hemicolectomy with standard laparoscopic instrumentation. METHOD: Between June 2010 and December 2011, 25 patients presenting with malignant disease underwent single-incision laparoscopy for right hemicolectomy. Four different ports (SILSTM port, Covidien; SSL((r)) Access system, Ethicon; X-Cone/S Portal((r)) , Storz; and OCTOTM port, AFS Medical) were used. Patients were recruited prospectively and all data were processed retrospectively. RESULTS: Twenty-five patients were included in our study (and their characteristics, described later in this paragraph, are expressed as median (range)). Four conversions to standard laparoscopy were performed. The age of patients was 69 (36-89) years, and they had a body mass index (BMI) of 24.5 (19.1-34.2). The duration of surgery was 110 (70-148) min with a healed skin incision length of 35 (20-60) mm. Hospital stay was 5 (2-15) days. In four patients discharge was delayed because of comorbidity. One patient suffered an overwhelming pneumonia. CONCLUSION: Single-incision laparoscopy using standard laparoscopic instruments appears to be a safe and feasible technique for malignant disease requiring right hemicolectomy. Randomized, prospective trials are ongoing to prove the benefits of this technique and to compare its oncological outcome measures with those of conventional laparoscopy. In our experience, a low-profile port with a wide intra abdominal range of motion is most preferable. PMID- 22776289 TI - Identifying characteristics associated with performing recommended practices in maternal and newborn care among health facilities in Rwanda: a cross-sectional study. AB - BACKGROUND: Although rates of maternal and neonatal mortality have decreased in many countries over the last two decades, they remain unacceptably high, particularly in sub-Saharan Africa. Nevertheless, we know little about the quality of facility-based maternal and newborn care in low-income countries and little about the association between quality of care and health worker training, supervision, and incentives in these settings. We therefore sought to examine the quality of facility-based maternal and newborn health care by describing the implementation of recommended practices for maternal and newborn care among health care facilities. We also aimed to determine whether increased training, supervision, and incentives for health workers were associated with implementing these recommended practices. We chose to study these aims in the Republic of Rwanda, where rates of maternal and newborn mortality are high and where substantial attention is currently focused on strengthening health workforce capacity and quality. METHODS: We used data from the 2007 Rwanda Service Provision Assessment. Using observations from 455 facilities and interviews from 1357 providers, we generated descriptive statistics to describe the use of recommended practices and frequencies of provider training, supervision, and incentives in the areas of antenatal, delivery, and newborn care. We then constructed multivariable regression models to examine the associations between using recommended practices and health provider training, supervision, and incentives. RESULTS: Use of recommended practices varied widely, and very few facilities performed all recommended practices. Furthermore, in most areas of care, less than 25% of providers reported having had any pre-service or in service training in the last 3 years. Contrary to our hypotheses, we found no evidence that training, supervision, or incentives were consistently associated with using recommended practices. CONCLUSION: Our findings highlight the need to improve facility-based maternal and newborn care in Rwanda and suggest that current approaches to workforce training, supervision, and incentives may not be adequate for improving these critical practices. PMID- 22776290 TI - Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture. AB - Over the recent years, various materials have been introduced as potential 3D cell culture scaffolds. These include protein extracts, peptide amphiphiles, and synthetic polymers. Hydrogel scaffolds without human or animal borne components or added bioactive components are preferred from the immunological point of view. Here we demonstrate that native nanofibrillar cellulose (NFC) hydrogels derived from the abundant plant sources provide the desired functionalities. We show 1) rheological properties that allow formation of a 3D scaffold in-situ after facile injection, 2) cellular biocompatibility without added growth factors, 3) cellular polarization, and 4) differentiation of human hepatic cell lines HepaRG and HepG2. At high shear stress, the aqueous NFC has small viscosity that supports injectability, whereas at low shear stress conditions the material is converted to an elastic gel. Due to the inherent biocompatibility without any additives, we conclude that NFC generates a feasible and sustained microenvironment for 3D cell culture for potential applications, such as drug and chemical testing, tissue engineering, and cell therapy. PMID- 22776292 TI - Co-evolution of departmental research collaboration and scholarly outcomes. AB - RATIONALE: Understanding scientific collaboration networks can assist research centres to develop strategies to maximize productivity, and help diagnose the causes of low system productivity. The purpose of this study was to use social network analysis to better understand how research collaboration within a productive department impacts scholarly productivity individually and departmentally. METHODS: Over a 13-year period, departmental faculty completed an annual survey describing their research collaborations and scholarly productivity. Data were analyzed using social network analysis. Quadratic assignment procedure regression assessed the predictive value that an individual's measures of centrality within the network and effective size of their own network (egonet) had each year in predicting each scholarly outcome. Simulation Investigation for Empirical Network Analysis software assessed the co evolution of the collaborative network and scholarship. RESULTS: While no consistent patterns for individual's presentations were seen, individual's publications were associated with betweenness and eigenvector centrality, and effective egonet size. Grant submissions were associated with degree and eigenvector centrality, as well as effective egonet size. Departmentally, network dynamics depended upon the scholarship of those around you, but none of the forms of scholarship depended upon network characteristics. Of the three forms of scholarship, network dynamics depended primarily on publications in others. CONCLUSION: Although individual scholarship was dependent upon individual centrality and effective egonet size, research collaboration within the department depended upon reciprocity, transitivity and scholarly productivity of its constituent investigators. Scholarly dynamics, at a departmental level, did not depend upon network characteristics. PMID- 22776291 TI - The cargo of CRPPR-conjugated liposomes crosses the intact murine cardiac endothelium. AB - Ligand-conjugated liposomes and other nano-sized constructs are attractive drug carriers due to their extended plasma circulation; however, limited data are available as to whether their cargo can traverse the endothelium of solid organs. To determine whether the cargo of endothelially targeted liposomes is internalized by endothelial cells and transported into tissue, and to evaluate whether such liposomes can accumulate in models of cardiovascular disease, we tracked the fate of the cargo (a hydrophilic fluorescent dye) and shell (conjugated with a radioisotope) of a heart-homing liposome (CRPPR-conjugated). The ex vivo heart was imaged with confocal microscopy and the in vivo heart with positron emission tomography in sham-treated mice and models of ischemia/reperfusion (I/R) and myocardial infarction (MI). Within 30 min of injection of 20mg/kg CRPPR liposomes, fluorescence increased by 47 fold in the tissue surrounding the vascular lumen, as compared with non-targeted liposomes. Both the accumulation on the endothelium and the interstitial fluorescence saturated at an injected dose of 20mg/kg. In both I/R and MI models, CRPPR liposomes accumulated in diseased sites, although less than in surrounding healthy tissue. The accumulation in the diseased sites increased with time post injury: the ratio of accumulated radioactivity in the diseased and healthy cardiac tissue increased from 0.20+/-0.04, to 0.58+/-0.12 and 0.61+/-0.19 for 1, 7, and 99 days post-MI, indicating the potential for adequate delivery and therapeutic efficacy if the targeted particles are injected at 7 or more days post-MI. In summary, CRPPR- liposomes accumulated in normal and diseased hearts, and the cargo accumulated in the tissue within minutes and remained detectable after 24 h. PMID- 22776293 TI - Electrical synapses between AII amacrine cells in the retina: Function and modulation. AB - Adaptation enables the visual system to operate across a large range of background light intensities. There is evidence that one component of this adaptation is mediated by modulation of gap junctions functioning as electrical synapses, thereby tuning and functionally optimizing specific retinal microcircuits and pathways. The AII amacrine cell is an interneuron found in most mammalian retinas and plays a crucial role for processing visual signals in starlight, twilight and daylight. AII amacrine cells are connected to each other by gap junctions, potentially serving as a substrate for signal averaging and noise reduction, and there is evidence that the strength of electrical coupling is modulated by the level of background light. Whereas there is extensive knowledge concerning the retinal microcircuits that involve the AII amacrine cell, it is less clear which signaling pathways and intracellular transduction mechanisms are involved in modulating the junctional conductance between electrically coupled AII amacrine cells. Here we review the current state of knowledge, with a focus on the recent evidence that suggests that the modulatory control involves activity-dependent changes in the phosphorylation of the gap junction channels between AII amacrine cells, potentially linked to their intracellular Ca(2+) dynamics. This article is part of a Special Issue entitled Electrical Synapses. PMID- 22776294 TI - Role of gamma-delta T cells in host response against Staphylococcus aureus induced pneumonia. AB - BACKGROUND: Staphylococcus aureus is the major cause of hospital-acquired and community-acquired pneumonia. Host defense to S.aureus infection is largely mediated by the innate immune system. gammadelta T cells play an important role in innate immunity to many infectious diseases. However, less is known about the role of these cells during S.aureus-induced pneumonia. In this study, we examined the response and the role of gammadelta T cells to pulmonary S.aureus infection. RESULTS: Mice infected with S. aureus intranasally showed rapid gammadelta T cells accumulation in the lung. Deficiency of gammadelta T cells led to attenuated bacterial clearance and less tissue damage in lung compared with WT mice. Moreover, TCR-delta-/- mice exhibited impaired neutrophil recruitment and reduced cytokine production at the site of infection. The gammadelta T cells in response to pulmonary S. aureus infection mainly secreted IL-17 and gammadelta T cells deficiency reduced IL-17 production, which might regulate the production of neutrophil-inducing cytokine/chemokine in the S. aureus-infected lungs. CONCLUSIONS: Accumulation of gammadelta T cells in the lungs to S. aureus infection is beneficial for bacteria clearance and also contributes to the tissue damage. These cells were the primary source of IL-17, which might influence the recruitment of neutrophils at the early stage of infection. PMID- 22776295 TI - Efficient oxidative folding and site-specific labeling of human hepcidin to study its interaction with receptor ferroportin. AB - Hepcidin is a small disulfide-rich peptide hormone that plays a key role in the regulation of iron homeostasis by binding and mediating the degradation of the cell membrane iron efflux transporter, ferroportin. Since it is a small peptide, chemical synthesis is a suitable approach for the preparation of mature human hepcidin. However, oxidative folding of synthetic hepcidin is extremely difficult due to its high cysteine content and high aggregation propensity. To improve its oxidative folding efficiency, we propose a reversible S-modification approach. Introduction of eight negatively charged sulfonate moieties into synthetic hepcidin significantly decreased its aggregation propensity and, under optimized conditions, dramatically increased the refolding yield. The folded hepcidin displayed a typical disulfide-constrained beta-sheet structure and could induce internalization of enhanced green fluorescent protein (EGFP) tagged ferroportin in transfected HEK293 cells. In order to study interactions between hepcidin and its receptor ferroportin, we propose a general approach for site-specific labeling of synthetic hepcidin analogues by incorporation of an L propargylglycine during chemical synthesis. Following efficient oxidative refolding, a hepcidin analogue with Met20 replaced by L-propargylglycine was efficiently mono-labeled by a red fluorescent dye through click chemistry. The labeled hepcidin was internalized into the transfected cells together with the EGFP-tagged ferroportin, suggesting direct binding between hepcidin and ferroportin. The labeled hepcidin was also a suitable tool to visualize internalization of overexpressed or even endogenously expressed ferroportin without tags. We anticipate that the present refolding and labeling approaches could also be used for other synthetic peptides. PMID- 22776296 TI - Total hip arthroplasty in a patient with congenital insensitivity to pain: a case report. AB - INTRODUCTION: Congenital insensitivity to pain, a rare neurological entity, is characterized by varying degrees of sensory loss and autonomic dysfunction. Orthopedic manifestations of congenital insensitivity to pain include delayed diagnosis of fractures, nonunions, malunions, Charcot arthropathy, acro osteolysis, avascular necrosis, osteomyelitis, heterotopic ossification and joint dislocations. We here report the case of a patient with congenital insensitivity to pain who had multiple lower extremity fractures at varying intervals, the most recent being a femoral neck fracture managed by total hip replacement. To the best of our knowledge, this is the first report of cementless hip arthroplasty in such a patient. CASE PRESENTATION: A 37-year-old Caucasian woman was admitted to our hospital complaining of painless swellings in her lower limb and limping. She had been diagnosed with multiple lower extremity fractures at different times. On physical examination, we found multiple perioral mucosal ulcers, shortening of her nails and acro-osteolysis, a prematurely aged facial appearance, undersized skeletal structure, Charcot arthropathy of her right ankle, anosmia, insensitivity to temperature differences and evidence of mild intellectual disability. A right subtrochanteric femur fracture was treated with an intramedullary nail. Eighteen months later, she presented with similar symptoms and we diagnosed a right femoral neck fracture. We removed the nail and performed cementless total right hip arthroplasty. CONCLUSIONS: Congenital insensitivity to pain is a rare condition that is associated with severe orthopedic problems. This case report, which will be of particular interest to orthopedic surgeons, presents several difficulties in the management of patients with congenital insensitivity to pain and notes the importance of close follow-up and early recognition of complications. Cementless total hip arthroplasty may be a good therapeutic option for femoral neck fracture in these patients. PMID- 22776297 TI - The cell adhesion and proliferation activities of a peptide derived from human tenascin-C are dependent on two Ile residues. AB - A tenascin-C derived peptide (TNIIIA2 peptide, 1) stimulated beta1 integrin mediated cell adhesion via binding to syndecan-4. Ala-substituted peptides were synthesized to understand the structure-activity relationship. Peptides in which basic amino acids were substituted showed reduced cell adhesion activity, but their proliferation activities were similar to or higher than those mediated by peptide 1. In contrast, peptides in which the Ile residues of peptide 1 were replaced were inactive, indicating that the Ile residues are critical for the peptide's activity. CD analysis suggested that the Ile residues are necessary for the formation of a specific conformation required for binding to syndecan-4. PMID- 22776298 TI - Anti-proliferative effects of a novel isoflavone derivative in medullary thyroid carcinoma: an in vitro study. AB - Currently available treatments for patients with medullary thyroid carcinoma (MTC) with residual or recurrent disease after primary surgery have low efficacy rates. In view of the possible role of estrogen in the development of thyroid neoplasia, we explored whether proliferation of the human MTC TT cell line, might be curbed by carboxy-daidzein-tBoc (cD-tBoc), a novel isoflavone derivative. Estrogen receptor (ER) alpha mRNA expression in TT cells was more abundant than ERbeta, with a ratio of 48:1. Estradiol-17beta (E2) increased DNA synthesis in a dose dependent manner. [(3)H]-thymidine incorporation was also stimulated by the ERbeta agonist DPN and the ERalpha agonist PPT. cD-tBoc inhibited TT cell growth as assessed by thymidine incorporation, XTT assay, and microscopic analysis of culture wells. Creatine kinase specific activity, a marker of the modulatory effects of estrogen on cell energy metabolism, was likewise inhibited. The inhibitory effect of cD-tBoc on [(3)H]-thymidine incorporation could be blocked by the ERbeta antagonist PTHPP but not by the ERalpha antagonist MPP, suggesting that the antiproliferative effect of cD-tBoc on these cells is mediated through ERbeta. Furthermore, cD-tBoc potently increased apoptosis and cell necrosis. Co incubation with the antiapoptotic agent Z-VAD-FMK reversed the growth inhibitory effect elicited by cD-tBoc. These results support the hypothesis that estrogens are involved in the proliferation of MTC. The potent anti-proliferative effects mediated by isoflavone derivatives in the human MTC cell line TT suggest and that this property may be utilized to design effective anti-neoplastic agents. PMID- 22776299 TI - Video-assisted thoracic surgery for lung cancer in hemodialysis patients. AB - INTRODUCTION: In recent years, the number of hemodialysis patients has been continuously increasing. At the same time, the use of video-assisted thoracic surgery (VATS) for lung cancer has also increased. However, reports of the outcome of VATS in hemodialysis patients are still quite rare. METHODS: From 1995 to 2011, 14 patients with non-small cell lung cancer who were also receiving hemodialysis underwent lung resection by open thoracotomy or VATS at our institution. These patients were divided into two groups as follows: open (five men and four women, mean age: 68.7 years) and (2) VATS (three men and two women, mean age: 64.0 years). We compared the clinical outcomes of these two groups. RESULTS: Lobectomy was performed in eight patients in the open group, including one patient who also underwent a pneumonectomy, and in four patients in the VATS group, including one who also underwent a wedge resection. There were no significant difference between the groups' operation times, intraoperative blood loss, length of postoperative chest drainage, and length of postoperative hospitalization. There were no hospital deaths in either group. The 5-year survival rate was 42.9% in the open group and 37.5% in the VATS group. This difference was not significant (P=0.73). CONCLUSION: VATS lung resection for lung cancer patients on hemodialysis is considered an acceptable treatment modality, though the long-term survival rate of such patients is relatively low, which can be attributed to the diseases underlying the need for hemodialysis. PMID- 22776300 TI - Total abdominal hysterectomy versus laparoscopically-assisted vaginal hysterectomy versus total vaginal hysterectomy. AB - INTRODUCTION: While total abdominal hysterectomy (TAH) and total vaginal hysterectomy (TVH) are conventional procedures, we have actively introduced laparoscopically-assisted vaginal hysterectomy (LAVH) since its advent. This study was the first attempt to retrospectively compare the surgical results, including invasiveness, among the three methods of performing a hysterectomy. METHODS: The subjects included 1181 patients who underwent total hysterectomies (TAH, n=465; LAVH, n=629; TVH, n=87) due to uterine fibroids or uterine adenomyosis at our hospital between January 1995 and December 2009. The mean age, parity, weight of the removed uterus, operative time, blood loss, rates of intra- and post-operative complications, length of post-operative hospital stay, leukocyte count, and CRP and hemoglobin levels were compared. RESULTS: The operative time was significantly longer in the LAVH group than the other two groups. Blood loss was significantly greater in the TAH group than the LAVH and TVA groups. The rates of intra- and post-operative complications were significantly higher in the TAH group than the LAVH group. The CRP level and leukocyte count were significantly lower in the LAVH group than the TAH and TVH groups. CONCLUSION: LAVH can be applied to nulligravidas or patients with relatively large uteri and it is proved less invasive than TAH and TVH in this study. We recommend active application of LAVH. PMID- 22776301 TI - Single-incision transabdominal preperitoneal and totally extraperitoneal repair for inguinal hernia: early experience from a single center in Asia. AB - INTRODUCTION: Laparoscopic inguinal hernia repair is currently one of the most commonly performed minimally invasive surgical procedures. In recent years, single-incision operations have been developed to further reduce the invasiveness of the surgery. Herein, we report our early experience with single-incision laparoscopic inguinal hernia repair in Asia, with both the transabdominal preperitoneal (TAPP) and totally extraperitoneal (TEP) approaches. METHODS: This is a retrospective review of prospectively collected data on a cohort of consecutive patients with inguinal hernia who underwent single-incision laparoscopic inguinal hernia repair in a minimal access surgical center in Hong Kong between January 2010 and January 2011. RESULTS: Our cohort consists of 15 patients who underwent single-incision laparoscopic inguinal hernia; 13 were unilateral and two were bilateral hernias. The mean age was 59.8 years old (range, 28-74 years). The overall mean operative time was 59.53 min (range, 25 120 min). For unilateral hernia repair, the mean operative time was 56 min (range, 25-75 min) and 48.5 min (range, 41-55 min) for TAPP and TEP, respectively. In all cases single-incision laparoscopic hernia repair was successfully performed, no additional trocars were required, and there were no conversions to conventional laparoscopic or open inguinal hernia repair. All patients were discharged on the same day as the procedure. CONCLUSION: Single incision laparoscopic inguinal hernia is feasible in both TEP and TAPP approaches. The procedure should be performed by laparoscopic surgeons with a high level of experience in single-incision surgery. Further randomized trials should be performed to evaluate the full potential and clinical application of single-incision TAPP and TEP. PMID- 22776302 TI - A case report of small bowel perforation at colonoscopy. AB - The most dreaded complication of a colonoscopy is colonic perforation. Perforation of the small bowel following colonoscopy is extremely rare, especially if the procedure was performed without any therapeutic intervention. Herein we report a case of jejunal perforation following a routine surveillance colonoscopy. A literature review focusing on the proposed mechanism of perforation is included. PMID- 22776303 TI - Rectal duplication cyst successfully treated by laparoscopic total mesorectal excision using the prolapsing technique. AB - Congenital alimentary tract duplication is a rare disease. It most frequently occurs in the ileum, with the rectum being the rarest site. Herein, we report a 38-year-old woman who was referred to our hospital because of severe anal pain. On digital examination, a smooth, round, rubbery mass was palpable; it was located 5 cm from the anal verge in the posterior rectal wall. A CT scan demonstrated a 5-cm cystic lesion located anterior to the sacrum that was displacing the rectum anteriorly. Spontaneous remission of the tumor was evident; however, after 5 months of follow-up, the patient experienced the same severe anal pain. MRI demonstrated a recurrent cystic lesion. To prevent further complications and to confirm or deny malignancy, laparoscopic total mesorectal excision using the prolapsing technique was performed. Pathologically, the cystic lesion was diagnosed as a rectal duplication cyst. This is the first report of a rectal duplication cyst successfully treated by laparoscopic total mesorectal excision. PMID- 22776304 TI - Cecal schwannoma with laparoscopic wedge resection: report of a case. AB - Schwannomas of the large intestine are relatively rare. Here, we present a case of schwannoma of the cecum in a 59-year-old woman that was successfully resected by laparoscopic wedge resection. In a medical checkup, a colonoscopy revealed a 2 cm submucosal lesion, without mucosal changes, located in the cecum wall contralateral to Bauhin's valve. Abdominal contrast CT and contrast MRI indicated a smooth-surfaced, semi-round tumor of about 2 cm that gave an enhanced homogeneous signal in the cecum. Laparoscopic wedge resection was performed after the diagnosis of benign submucosal tumor. The lesion was 2.5 * 2.0 cm, was histologically composed of spindle neoplastic cells arranged in cords, was positive for S-100 and vimentin, and was diagnosed as schwannoma. The details of this case are reported herein and focus on the successful application of laparoscopic wedge resection for treatment of the colonic submucosal lesion. PMID- 22776305 TI - Inflammatory pseudotumor of the liver in association with spilled gallstones 3 years after laparoscopic cholecystectomy: report of a case. AB - We report on a case of a female patient diagnosed with inflammatory pseudotumor of the liver in association with spilled gallstones 3 years after laparoscopic cholecystectomy for calculous acute cholecystitis. She was asymptomatic, but CT revealed an intrahepatic mass and two other extrahepatic masses between the liver and the diaphragm. Furthermore, diffusion-weighted MRI and PET suggested all three lesions could be malignant tumors. As the preoperative diagnosis was intrahepatic cholangiocellular carcinoma with peritoneal disseminations, we performed a posterior segmentectomy of the liver combined with partial resection of the diaphragm. Histological examination showed the intrahepatic tumor was an inflammatory granuloma with abscess formations. There were bilirubin stones between the liver and the diaphragm. Therefore, the tumor was diagnosed as inflammatory pseudotumor of the liver in association with spilled gallstones. In conclusion, the liver tumor emerged after laparoscopic cholecystectomy and may involve inflammatory pseudotumor of the liver in association with spilled gallstones. PMID- 22776306 TI - Laparoscopy-assisted spleen-preserving pancreatic resection for epidermoid cyst in an intrapancreatic accessory spleen. AB - A rare case of an epidermoid cyst originating in an intrapancreatic accessory spleen in a 50-year-old Japanese female is reported. A hypoechoic cystic tumor was detected incidentally by abdominal ultrasonography. It appeared to be a single cyst in the pancreatic tail with a contrasted mass lesion beside it. Laparoscopy-assisted spleen-preserving pancreatic tail resection was performed. Microscopic examination revealed that the cyst was surrounded by fibrous tissue and a thin layer of splenic tissue, adjacent to normal pancreatic parenchyma. The inner surface of the cyst was lined with non-keratinizing squamous epithelium. The diagnosis of an epidermoid cyst occurring in an intrapancreatic accessory spleen was confirmed. Laparoscopy-assisted spleen-preserving pancreatic resection is a safe and effective procedure for benign or low-grade malignant cystic diseases in the pancreas. PMID- 22776307 TI - Laparoscopic Roux-en-Y gastric bypass in a morbidly obese patient with renal transplant: a case report. AB - Renal transplant is the only curative treatment for end-stage renal disease. As diabetes and obesity are the major causes of graft failure and post-transplant complication, it is important to manage obesity in patients with renal transplant. Herein, we report a case of a morbidly obese renal-transplant patient with poorly controlled diabetes who received bariatric surgery. A 34-year-old obese Taiwanese man with type 2 diabetes had end-stage renal disease that had progressed since 2008, when he had commenced hemodialysis (January 2008) and had a renal transplant (July 2008). Because of persistent obesity and poorly controlled diabetes, he received LRYGB at Chiayi Christian hospital on 18 August 2010. In the month that followed, he lost 10 kg. His serum creatinine decreased to 1.11 mg/dL (1.4 mg/dL, preoperative) and his hemoglobin A1c decreased to 8.5% (10.4%, preoperative). These results indicate that, in obese renal transplant patients, LRYGB may be employed to treat obesity, control diabetes and stabilize or improve the renal function. PMID- 22776308 TI - Delayed left traumatic diaphragmatic hernia repaired by laparoscopic surgery. AB - A 77-year-old man injured himself when he fell heavily on the left side of his chest. He had massive subcutaneous emphysema, bleeding, and left hemopneumothorax. He also fractured his seventh through tenth ribs; a fragment of the ninth rib was displaced into the thoracic cavity. The severity of the damage and the patient's pain was assessed using the Abbreviated Injury Scale 1990 (1998 update) as level 3. He was treated with conservative therapy and discharged on the 16 days after the injury. However, the following day, he had acute upper abdominal pain, his blood pressure dropped to 40 s, and he was readmitted. A chest CT showed the transverse colon was prolapsed in the thoracic cavity. The patient was diagnosed as having a delayed traumatic diapharagmatic hernia. A laparoscopic repair was performed. The rupture was classified as a IIIb-type diaphragmatic injury according to the Japanese Association for the Surgery of Trauma's classification system. It is believed that a fragment of a fractured rib that had been displaced in the thoracic cavity ruptured the diaphragm sharply. Since traumatic diapharagmatic hernia rarely occurs, it is relatively difficult to diagnose at the first examination. This condition has a high mortality rate because of the associated injuries. Surgery is the only treatment, but it should only be considered after a second examination. Herein, I report my experience with a case of delayed diaphragmatic hernia repaired by laparoscopic surgery. PMID- 22776309 TI - Transanal radical endoscopic resection of the rectum on a swine model: a surviving model. AB - INTRODUCTION: This multimedia video is the second part of our study on transanal endoscopic radical resection of the rectum, which we have previously described (http://links.lww.com/DCR/A4). In this present study, we hypothesized that this procedure is not only technically feasible but also safe. MATERIALS AND SURGICAL TECHNIQUE: This procedure was performed on two swine as a surviving model. After radical resection of the rectum and primary anastomosis, the two swine were monitored in an animal holding area for a period of 1 week, and the anastomoses were inspected after that period. The lower rectum was transected, and retroperitoneal dissection was performed transanally using flexible endoscopic equipment to achieve high ligation of the caudal mesenteric vessels. After rectal resection, hand-sewn coloanal anastomosis was performed. DISCUSSION: Both swine had good postoperative outcomes, and the postoperative period was captured on video. Transanal radical endoscopic resection of the rectum is not only technically feasible, but it can can be safely performed on swine. PMID- 22776310 TI - Laparoscopic common hepatic artery ligation and staging followed by distal pancreatectomy with en bloc resection of celiac artery for advanced pancreatic cancer. AB - INTRODUCTION: Adeno-carcinomas of pancreatic body are usually asymptomatic and progress to advanced stage with involvement of major arteries. Resection of advanced cancer along with en bloc resection of a common hepatic artery and celiac trunk enables a "curative" resections and only possible treatment. However, the celiac axis resection always has a risk of compromising blood supply to liver, resulting in the hepatic insufficiency. We evaluated practicability of a two-stage procedure for the advanced pancreases body cancer, laparoscopic clamping of a common hepatic artery followed by open distal pancreatectomy with en bloc celiac arterial resection to prevent the hepatic insufficiency. MATERIALS AND SURGICAL TECHNIQUE: Seventy-five-year-old woman diagnosed with a 50-mm pancreatic body mass, invading splenic artery, common hepatic artery, splenic vein, and portal vein at the confluence. STAGE-1: At laparoscopy, after confirming absence of the peritoneal, superficial liver metastases and negative peritoneal cytology; we approached the common hepatic artery through the lesser sac and ligated. STAGE-2: Her liver function tests were normal after 2 weeks, and CT angiography showed complete blockage of the common hepatic artery with sufficient collateral circulation to the liver through inferior pancreatico duodenal artery and gastro-duodenal artery. We performed an open distal pancreatectomy with en bloc resection of celiac artery. Histopathology examination confirmed R0 resection. DISCUSSION: The celiac axis resection with distal pancreatectomy improves the chance of R0 resection and potentially, survival of the patient. Preoperative laparoscopic ligation of the common hepatic artery is a safe, effective, and in-expensive technique to prevent postoperative hepatic insufficiency and improves the safety of en bloc celiac artery resection with a distal pancreatectomy. Also these patients have high risk of peritoneal dissemination. Diagnostic laparoscopy is useful to detect occult metastasis, which are missed by per-operative CT scan. PMID- 22776311 TI - An evaluation of the effectiveness of information literacy training for undergraduate midwives to improve their ability to access evidence for practice. AB - BACKGROUND: Several authors have suggested that computer skills should be taught within the undergraduate curriculum. In this paper, the focus is mainly on the results of an examination of midwifery students' search strategy in response to a specific question undertaken before and after training session in the first, second and third years of the undergraduate programme. METHODS: The intervention allocated 16 h of library-based instruction over the first three years of the programme focussing specifically on the skills required to utilise electronic resources effectively. Following ethical approval by the university, 108 undergraduates took part from 2008 to 2011. RESULTS: The data obtained from the search history files were categorised as either poor, fair or good. The primary analyses compared the pre and post-instruction categories in each year, within each student, with a comparison of each student's post-instruction category one year and the pre-instruction category the following year. The data indicated that the sessions in the first and second years of the programmes resulted in improvements in the ability to search, with less improvement in third year. CONCLUSIONS: As with any complex intervention, it is not possible to tease out which elements of the session were most beneficial. We will try to identify ways in which midwifery students' search skills could be strengthened further. PMID- 22776312 TI - Exosomes are endogenous nanoparticles that can deliver biological information between cells. AB - Exosomal particular size of 30-100 nm matches the size criterion for nanoparticles, and opens up the possibility of using exosomes as a nanoparticle drug carrier. More importantly, exosomes released from different types of host cells have different biological effects and targeting specificities. Therefore, depending on the therapeutic goal, different types of exosomes can be combined with specific drugs and serve as carriers so that personalized medicine needs are met. In addition, exosomes do not appear to have cytotoxicity. Based on the perceived advantages of exosomes, they may well serve as a next generation drug delivery mechanism that combines nanoparticle size with a non-cytotoxic effect, target specificity, and a high drug carrying capacity, to make them useful in the treatment of a variety of diseases. This review will focus on exosomes as a biological nanoparticle drug carrier with emphasis on their immune-regulatory activities. PMID- 22776313 TI - An approach towards realizing the intelligent sphygmogram sampling for e-home healthcare. AB - Pulse wave transit time (PWTT) method has been widely used in continuous blood pressure estimation by simultaneously measuring electrocardiogram and pulse signals in most researches [1]. Comparing with the morphological characteristic of photoplethysmograph (PPG) [2], the alternative sphygmogram (SPG) signal is much sharper and promising to improve the accuracy of onset point detection in PWTT estimation. Consequently, a hardware and software close-loop control scheme for SPG sampling with less distortion is proposed, through which the signal amplitude and baseline self-adjustment is realized such that the resulted SPG signal is more properly suitable for onset point detection. Testing results show out its superior features for adapting PWTT in e-home healthcare. PMID- 22776314 TI - Ex vivo Akt/HO-1 gene therapy to human endothelial progenitor cells enhances myocardial infarction recovery. AB - The aim of this study was to evaluate the overexpression of genes central to cell survival and angiogenesis to enhance the function of human late outgrowth endothelial progenitor cells (EPCs) and their utility for infarct recovery. Ischemic myocardial injury creates a hostile microenvironment, which is characterized by hypoxia, oxidative stress, and inflammation. The infarct microenvironment prevents adhesion, survival, and integration of cell transplants that promote neovascularization. EPCs are dysfunctional as a result of risk factors in cardiovascular patients. Protein kinase B (Akt) and heme-oxygenase-1 (HO-1) are intracellular proteins that play an important role in angiogenesis and cell survival. Late outgrowth EPCs transduced ex vivo with Akt and HO-1 demonstrate improved adhesion to extracellular matrix, improved migration toward human cardiomyocytes, and an improved paracrine profile under stress. Enhanced late outgrowth EPCs reduce the tumor necrosis factor-alpha (TNF-alpha) burden both in vitro and in vivo, attenuating nuclear factor-kappaB (NF-kappaB) activity and promoting cell survival. Akt and HO-1 enhance late outgrowth EPC neovascularization, resulting in improved cardiac performance and reduced negative remodeling after myocardial infarction in nude mice. Alteration of the infarct microenvironment through gene modification of human late outgrowth EPCs enhances the function and integration of transplanted cells for restoration of cardiac function. PMID- 22776315 TI - The most reliable probe position in the ultrasonographic examination of the wrist in rheumatoid arthritis. AB - OBJECTIVES: This study aims to evaluate the inter-observer reliability of the ultrasonographic examination of the wrist in RA patients between 3 examiners and 3 probe positions. METHODS: Fifty-three RA patients were recruited at the University Clinical Hospital of Santiago de Compostela in Spain for ultrasonographic examination of the wrist. Ultrasonography (US) was performed on both wrists using a GE LOGIQ 9 machine, using three probe positions: Lister's Tubercle to digit II (position 1), Lister's Tubercle to digit III (position 2) and ulnocarpal (position 3), from the anatomic medial orientation. Three examiners (2 experienced ultrasonographers and 1 junior ultrasonographer) scored synovitis according to a 0-3 semiquantitative scoring system. Inter-observer reliability was expressed using the ICC (A,1). RESULTS: For grey-scale ultrasound (GSUS) the inter-observer reliability (ICC(A,1)) (single measure, agreement definition) ranged from 0.35 for the ulnocarpal joint, position 3, to 0.60 in both position 1 for the radiocarpal joint and position 2 for the inter-carpal joint. Using power Doppler ultrasound (PDUS) the inter-observer reliability (ICC(A,1)) ranged from 0.36 in position 3, to 0.52 both in position 1 and 2 for the radiocarpal joint. CONCLUSIONS: The reliability of the GSUS-examination of the wrist joints of RA patients with GSUS shows highest, moderate reliability using the anatomical landmarks Tubercle of Lister and digit III (position 2). The reliability of the PDUS examination was similar and moderate in both position 1 (Lister's Tubercle to digit II) and position 2 (Lister's Tubercle to digit III). The reliability was poorest for position 3 (the anatomic medial view of the ulnocarpal joint) in both the GSUS and PDUS examination. This study suggests that position 2 should be used in clinical trials and daily practice. PMID- 22776316 TI - Health workers' attitudes toward immigrant patients: a cross-sectional survey in primary health care services. AB - BACKGROUND: Health workers' attitudes toward immigrant patients influence behaviour, medical decisions, quality of care and health outcomes. Despite the increasing number of immigrant patients in health services and the potential influence of health workers' attitudes, there is little research in this area. This study aimed to examine attitudes of different health workers' groups toward immigrant patients and to identify the associated factors. METHODS: This cross sectional study was conducted with a random sample of 400 health workers from primary health care services in the Lisbon region, Portugal. Among those, 320 completed a structured questionnaire. Descriptive analysis and multiple linear regression analysis were used for the evaluation of data. RESULTS: Most participants did not agree that immigrant patients tend to behave like victims, but about half considered that some are aggressive and dangerous. Doctors and nurses showed more positive attitudes than office workers. Among doctors, the older ones reported less positive attitudes compared to the younger ones. Health workers who have less daily contact with immigrants revealed more positive attitudes. Most participants evaluated their knowledge and competencies to work with immigrants as moderate or low. CONCLUSIONS: Although health workers reveal positive attitudes, this study reinforces the need to develop strategies that prevent negative attitudes and stereotyping in health services. Efforts should be made to improve workers' competencies to deal with culturally diverse populations, in order to promote quality of health care and obtain positive health outcomes among immigrant populations. PMID- 22776317 TI - Evaluation of risk equations for prediction of short-term coronary heart disease events in patients with long-standing type 2 diabetes: the Translating Research into Action for Diabetes (TRIAD) study. AB - BACKGROUND: To evaluate the U.K. Prospective Diabetes Study (UKPDS) and Framingham risk equations for predicting short-term risk of coronary heart disease (CHD) events among adults with long-standing type 2 diabetes, including those with and without preexisting CHD. METHODS: Prospective cohort of U.S. managed care enrollees aged >= 18 years and mean diabetes duration of more than 10 years, participating in the Translating Research into Action for Diabetes (TRIAD) study, was followed for the first occurrence of CHD events from 2000 to 2003. The UKPDS and Framingham risk equations were evaluated for discriminating power and calibration. RESULTS: A total of 8303 TRIAD participants, were identified to evaluate the UKPDS (n = 5914, 120 events), Framingham-initial (n = 5914, 218 events) and Framingham-secondary (n = 2389, 374 events) risk equations, according to their prior CHD history. All of these equations exhibited low discriminating power with Harrell's c-index <0.65. All except the Framingham initial equation for women and the Framingham-secondary equation for men had low levels of calibration. After adjsusting for the average values of predictors and event rates in the TRIAD population, the calibration of these equations greatly improved. CONCLUSIONS: The UKPDS and Framingham risk equations may be inappropriate for predicting the short-term risk of CHD events in patients with long-standing type 2 diabetes, partly due to changes in medications used by patients with diabetes and other improvements in clinical care since the Frmaingham and UKPDS studies were conducted. Refinement of these equations to reflect contemporary CHD profiles, diagnostics and therapies are needed to provide reliable risk estimates to inform effective treatment. PMID- 22776318 TI - Genome-wide study identifies the regulatory gene networks and signaling pathways from chondrocyte and peripheral blood monocyte of Kashin-Beck disease. AB - This investigation was designed to unravel gene networks in Kashin-Beck disease (KBD) and better identify target genes of KBD for gene therapy development. RNA was isolated separately from cartilage and peripheral blood samples of patients with KBD and healthy controls. Agilent 44K human whole-genome oligonucleotide microarrays were used to detect differentially expressed genes. Three significant canonical pathways and nine chondrocyte networks from chondrocytic gene expression profiles were screened using ingenuity pathway analysis (IPA), but only one network and no canonical pathways from peripheral blood monocytic gene profile were identified. Bak1, APAF-1, CASP6, IGFBP2, Col5a2 and TGFBI extracted from significant genes that involved in chondrocytic canonical pathways and networks may have closer relationship with the etiopathogenesis of KBD. Those genes may be potential targets for gene diagnosis and treatment. Six physiological functions were predominant and unique to the chondrocytic genes, whereas two were unique to peripheral blood monocytic genes. The identified genes may represent a source of potentially novel molecular targets, which may provide a better understanding of the molecular details in KBD pathogenesis and also provide useful pathways and network maps for the future research in osteochondrosis. PMID- 22776319 TI - Multiple granulomatous lung lesions in a patient with Epstein-Barr-virus-induced mononucleosis and new-onset systemic lupus erythematosus: a case report. AB - INTRODUCTION: Granulomatous lesions are commonly encountered abnormalities in pulmonary pathology, and often pose a diagnostic challenge. We report an unusual case of granulomatous lung disease with uncommon characteristics, which developed following Epstein-Barr-virus-induced mononucleosis and new-onset systemic lupus erythematosus. We aim to highlight a diagnostic approach for the condition and to raise awareness of the possibility of it being related to the immunological reaction caused by Epstein-Barr virus infection. CASE PRESENTATION: A 36-year-old Japanese man, who had been diagnosed with Epstein-Barr-virus-induced infectious mononucleosis, new-onset systemic lupus erythematosus, and secondary Sjogren's syndrome three weeks previously, presented to our facility with fever and diffuse pulmonary infiltrates. A computed tomography scan of the chest revealed multiple small nodules in both lungs. Fiberoptic bronchoscopy with bronchoalveolar lavage revealed lymphocytosis with predominance of T lymphocytes. A histological examination of a lung biopsy taken during video-assisted thoracic surgery showed randomly distributed tiny granulomatous lesions with infiltration of eosinophils. The differential diagnoses included hypersensitivity pneumonitis, sarcoidosis, and pulmonary involvement of Crohn's disease, systemic lupus erythematosus, and Sjogren's syndrome, but the clinical and pathological findings were not consistent with any of these. Our patient's condition did not improve; therefore, prednisolone therapy was started because of the possibility of specific immunological reactions associated with Epstein-Barr virus infection. After steroid treatment, our patient showed radiological and clinical improvement. CONCLUSIONS: To the best of our knowledge, this is the first case of a patient developing randomly distributed multiple granulomatous lung lesions with eosinophilic infiltrates after Epstein-Barr virus infection and systemic lupus erythematosus. On the basis of our data, we hypothesize that Epstein-Barr virus infection altered the immune response of our predisposed patient and contributed to the pathogenesis of the lung lesions. Our patient's clinical response to steroid treatment was excellent. PMID- 22776320 TI - Comparative analysis of diguanylate cyclase and phosphodiesterase genes in Klebsiella pneumoniae. AB - BACKGROUND: Klebsiella pneumoniae can be found in environmental habitats as well as in hospital settings where it is commonly associated with nosocomial infections. One of the factors that contribute to virulence is its capacity to form biofilms on diverse biotic and abiotic surfaces. The second messenger Bis (3'-5')-cyclic dimeric GMP (c-di-GMP) is a ubiquitous signal in bacteria that controls biofilm formation as well as several other cellular processes. The cellular levels of this messenger are controlled by c-di-GMP synthesis and degradation catalyzed by diguanylate cyclase (DGC) and phophodiesterase (PDE) enzymes, respectively. Many bacteria contain multiple copies of these proteins with diverse organizational structure that highlight the complex regulatory mechanisms of this signaling network. This work was undertaken to identify DGCs and PDEs and analyze the domain structure of these proteins in K. pneumoniae. RESULTS: A search for conserved GGDEF and EAL domains in three sequenced K. pneumoniae genomes showed that there were multiple copies of GGDEF and EAL containing proteins. Both single domain and hybrid GGDEF proteins were identified: 21 in K. pneumoniae Kp342, 18 in K. pneumoniae MGH 78578 and 17 in K. pneumoniae NTUH-K2044. The majority had only the GGDEF domain, most with the GGEEF motif, and hybrid proteins containing both GGDEF and EAL domains were also found. The I site for allosteric control was identified only in single GGDEF domain proteins and not in hybrid proteins. EAL-only proteins, containing either intact or degenerate domains, were also identified: 15 in Kp342, 15 in MGH 78578 and 10 in NTUH-K2044. Several input sensory domains and transmembrane segments were identified, which together indicate complex regulatory circuits that in many cases can be membrane associated. CONCLUSIONS: The comparative analysis of proteins containing GGDEF/EAL domains in K. pneumoniae showed that most copies were shared among the three strains and that some were unique to a particular strain. The multiplicity of these proteins and the diversity of structural characteristics suggest that the c-di-GMP network in this enteric bacterium is highly complex and reflects the importance of having diverse mechanisms to control cellular processes in environments as diverse as soils or plants and clinical settings. PMID- 22776321 TI - Cell-free expression of disulfide-containing eukaryotic proteins for structural biology. AB - We describe Escherichia coli based cell-free production of milligram quantities of eukaryotic proteins containing native disulfide bonds. Using a previously described expression system, we systematically investigated the influence of redox potential variation in the reaction mixture and the impact of adding disulfide bond catalysts on soluble protein production. It is then shown that the optimized reaction conditions for native disulfide bond formation can be combined with the use of N-terminal fusion constructs with the GB1 domain for increased expression yields. The resulting cell-free system is suitable for stable-isotope labeling and does not require chemical pretreatment of the cell extract to stabilize the redox potential. For the human doppel protein, the mouse doppel protein and mouse interleukin-22 we obtained 0.3-0.7 mg of purified native protein per milliliter of reaction mixture. Formation of disulfide bonds was validated using the Ellman assay, and native folding of the three proteins was monitored by NMR and CD spectroscopy. PMID- 22776323 TI - Structural complexity in isoprenoid glycerol dialkyl glycerol tetraether lipid cores of Sulfolobus and other archaea revealed by liquid chromatography-tandem mass spectrometry. AB - Liquid chromatography-tandem mass spectrometry of membrane lipid cores from Sulfolobus species reveals isomeric forms of ring-containing isoprenoid glycerol dialkyl glycerol tetraether components not previously recognised via the use of NMR and liquid chromatography-mass spectrometry techniques. Equivalent isomerism was confirmed for the components in other hyperthermophilic genera and in sediments which contain the lipids of mesophilic archaea. The recognition of the isomeric structures in distinct archaeal clades suggests that profiles of tetraether lipids reported previously may have oversimplified the true lipid complexity in archaeal cultures and natural environments. Accordingly, the extent of variation in tetraether structures revealed by the work should direct more informative interpretations of lipid profiles in the future. Moreover, the results emphasise that tandem mass spectrometry provides a unique capability for assigning the structures of intact tetraether lipid cores for co-eluting species during chromatographic separation. PMID- 22776322 TI - Sphincter-sparing anal-fissure surgery: a 1-year prospective, observational, multicentre study of fissurectomy with anoplasty. AB - AIM: Internal sphincterotomy is the standard surgical treatment for chronic anal fissure, but is frequently complicated by anal incontinence. Fissurectomy is proposed as an alternative technique to avoid sphincter injury. We describe 1 year outcomes of fissurectomy. METHOD: This was a prospective, multicentre, observational study. All patients with planned surgery for chronic anal fissure were included and had fissurectomy. Data were collected before surgery, at healing, and 1 year after fissurectomy. Patient self-assessed anal symptoms and quality of life (using the 36-item short-form health survey [SF-36] questionnaire). Presurgical and postsurgical variables were compared using the Wilcoxon signed-rank test for paired samples. RESULTS: Two-hundred and sixty-four patients were included (median age, 45 years; 52% women). Anoplasty was associated with fissurectomy in 83% of the 257 documented cases. The main complications were urinary retention (n = 3), local infection (n = 4) and faecal impaction (n = 1). Healing was achieved in all patients at a median of 7.5 weeks after surgery. No recurrence occurred. At 1 year, 210 (79%) questionnaires were returned. Median anal pain had dropped from 7.3/10 to 0.1/10 (P < 0.001), anal discomfort had decreased from 5.0/10 to 0.1/10 (P < 0.001) and the Knowles Eckersley-Scott Symptom constipation score had decreased from 9/45 to 5/45 (P < 0.001). There was a nonsignificant increase in the Wexner anal incontinence score, from 1/20 to 2/20. De-novo clinically significant anal incontinence (Wexner score > 5) affected 7% of patients at 1 year, but presurgical incontinence had disappeared in 15% of patients. All SF-36 domains significantly improved. Anoplasty did not impact any result. CONCLUSION: Given its high rate of healing and low rate of de-novo anal incontinence, fissurectomy with anoplasty is a valuable sphincter-sparing surgical treatment for chronic anal fissure. PMID- 22776324 TI - The impact of a dam on the helminth fauna and health of a neotropical fish species Salminus brasiliensis (Cuvier 1816) from the upper Parana River, Brazil. AB - The aim of the present study was to detect changes in the structure of the helminth parasite infracommunities in Salminus brasiliensis (Cuvier 1816) from the floodplain of the upper Parana River after construction of the Porto Primavera Hydroelectric Plant. A total of 126 fish in the period before the dam's construction and 56 specimens 10 years after this event were analysed. Three species of parasites were collected before the construction of the dam: Prosthenhystera obesa Diesing, 1850 (Digenea), Cladocystis intestinalis Vaz, 1932 (Digenea) and Monticellia coryphicephala Monticelli, 1892 (Cestoda), and one nematode species in the larval stage, whose identification was not possible. After dam construction, the following helminth parasites were found: C. intestinalis, M. coryphicephala, Octospiniferoides incognita, Contracaecum spp. larvae and Contracaecum sp. type 2 larvae Moravec, Kohn & Fernandes 1993. The diversity of helminth parasites measured by the Brillouin diversity index (HB) differed significantly between the pre- and post-dam periods (mean HB = 0.069 and HB = 0.2, respectively; P= 0.0479; Mann-Whitney U test). The parasite community of S. brasiliensis before the construction of the dam showed concentration of dominance (C) of P. obesa (C = 0.38), while there was no concentration of dominance of any species of parasite (C = 0.22) after the dam's construction. Before the Porto Primavera dam the relative condition factor of fish was 1.0; after the dam's construction it was 0.93 (P < 0.0001; Mann-Whitney U test). This study records the disappearance of the species P. obesa and suggests that there has been local extinction of this parasite. The results show that the anthropic influence on natural systems is interfering with the welfare and health of S. brasiliensis, reflected by its fauna of helminth parasites. PMID- 22776325 TI - Long term exposure to organochlorine pesticides and thyroid function in children from Cidade dos Meninos, Rio de Janeiro, Brazil. AB - A pesticide factory in Cidade dos Meninos village, Duque de Caxias County, Rio de Janeiro, Brazil, ended its activity in 1961, leading to widespread contamination of the environment by several organochlorine pesticides. The aim of this study was to investigate the effects of chronic exposure to organochlorine pesticides on thyroid hormone levels in children residing in Cidade dos Meninos. In a population-based survey carried out between 2003 and 2004, serum concentration of 19 pesticides and levels of free thyroxine (T4), total triiodothyronine (T3) and thyroid-stimulating hormone (TSH) were determined in 193 children younger than 15 years old. Multivariate linear regression was conducted to examine thyroid hormone levels according to quintiles of organochlorine exposure, controlling for age, gender and serum lipid content. Free T4 and TSH levels were within reference values (0.7-1.8 ng/dl and 0.35-5.5 mU/l), whereas total T3 was above the reference range (80-180 ng/dl) in 28% of children. More than 60% of the children had detectable levels of most organochlorine pesticides. With the exception of heptachlor and methoxychlor, total T3 levels showed a significant increasing linear trend regardless of pesticide type to which children were exposed. Free T4 levels were positively and significantly associated only with exposure to p,p' DDD, endosulfan 1, and dieldrin. No significant trend was found for TSH. Data showed that exposure of children to organochlorine pesticides produced a significant increase in serum total T3 concentrations. The clinical implications of such a total T3 elevation and subsequent development are uncertain and warrant the need for health monitoring of these children. PMID- 22776326 TI - Persistence of the bovine spongiform encephalopathy infectious agent in sewage. AB - Horizontal transmission of prion diseases through the environment represents a considerable concern. Prions are extremely resistant to inactivation and are thought to enter the environment after burial of animal mortalities or through biosolids from wastewater treatment plants. In addition, deposition of prions in the environment through biological fluids and/or faeces has been proved in the last years. Little is known about the behaviour of prion infectivity in the environment. In this study, the persistence of BSE infectious agent in sewage has been assessed by both PrP(Res) immunoblotting and mouse bioassay in a long-term incubation study. Results indicated that no PrP(Res) was detected after 150 day of incubation and consistent with this, a statistical regression model estimated 2-logs decay in 151 day. In contrast, no reduction in infectivity was observed during this period. Similarly, BSE infectivity remained unaltered after incubation in PBS for 265 day, whereas PrP(Res) levels dropped progressively over the length of the study. These results indicate that in sewage and PBS, prion infectivity persists longer and with different dynamics than its commonly used marker PrP(Res). Thus, mathematical models computed on the basis of PrP(Res) detection were unable to predict inactivation of prion infectivity. It is also reasonable to assume that conventional wastewater treatments with low retention times could have a very limited impact on prion infectivity. This data is essential for the development of accurate risk assessment analysis for BSE and other prion diseases in the environment. PMID- 22776327 TI - Personal exposure to specific volatile organic compounds and acute changes in lung function and heart rate variability among urban cyclists. AB - BACKGROUND: Few studies have examined the acute cardiorespiratory effects of specific volatile organic compound (VOC) exposures from traffic pollution. METHODS: A cross-over study was conducted among 42 healthy adults during summer 2010 in Ottawa, Canada. Participants cycled for 1-h along high and low-traffic routes and VOC exposures were determined along each route. Lung function, exhaled nitric oxide, and heart rate variability were monitored before cycling and 1-4h after the start of cycling. Bayesian hierarchical models were used to examine the relationship between 26 VOCs and acute changes in clinical outcomes adjusted for potential confounding factors. RESULTS: Each inter-quartile range (IQR) increase in propane/butane exposure was associated with a 2.0 millisecond (ms) (95% CI: 0.65, 3.2) increase in SDNN (standard deviation of normal-to-normal intervals), a 24 ms(2) (95% CI: 6.6, 41) increase in HF (high frequency power), and a 65 ms(2) (95% CI: 11, 118) increase in LF (low frequency power) in the hours following cycling. IQR increases in ethane and isoprene were associated with a 5.8 ms (95% CI: -9.8, -1.7): decrease in SDNN and a 24 ms(2) (95% CI: -44, -7.9) decrease in HF, respectively. IQR increases in benzene exposure were associated with a 1.7 ppb (95% CI: 1.1, 2.3) increase in exhaled nitric oxide and each IQR increase in 3-methylhexane exposure was associated with a 102 mL (95% CI: -157, -47) decrease in forced expiratory volume in 1-s. CONCLUSIONS: Exposure to traffic-related VOCs may contribute to acute changes in lung function, inflammation, or heart rate variability. PMID- 22776328 TI - Mineral image enhancement based on sequential combination of toggle and top-hat based contrast operator. AB - Enhancing mineral image especially making mineral image details clear is very useful for mineral analysis. To effectively enhance mineral image, an algorithm based on the toggle contrast operator and top-hat based contrast operator is proposed in this paper. Sequentially combining the toggle contrast operator and top-hat based contrast operator could be used to identify image features especially the image details. So, appropriately exacting the identified image features by the sequentially combined toggle and top-hat based contrast operator is important for mineral image enhancement, which is analyzed firstly in this paper. After that, the multi-scale extension of feature extraction is given and used to construct the final features for mineral image enhancement. By importing the final extracted image features into the original mineral image through contrast enlargement, the original mineral image is well enhanced and the mineral image details are very clear. Experimental results on different types of mineral images verified the effective performance of the proposed algorithm. PMID- 22776329 TI - Exendin-4, a glucagon-like peptide-1 receptor agonist, inhibits cell apoptosis induced by lipotoxicity in pancreatic beta-cell line. AB - Lipotoxicity plays an important role in the underlying mechanism of type 2 diabetes mellitus. Prolonged exposure of pancreatic beta-cells to elevated concentrations of fatty acid is associated with beta-cell apoptosis. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have been reported to have direct beneficial effects on beta-cells, such as anti-apoptotic effects, increased beta-cell mass, and improvement of beta-cell function. The mechanism of GLP-1 receptor agonists' protection of pancreatic beta-cells against lipotoxicity is not completely understood. We investigated whether the GLP-1 receptor agonist exendin-4 promoted cell survival and attenuated palmitate-induced apoptosis in murine pancreatic beta-cells (MIN6). Exposure of MIN6 cells to palmitate (0.4mM) for 24h caused a significant increase in cell apoptosis, which was inhibited by exendin-4. Exposure of MIN6 cells to exendin-4 caused rapid activation of protein kinase B (PKB) under lipotoxic conditions. Furthermore, LY294002, a PI3K inhibitor, abolished the anti-lipotoxic effect of exendin-4 on MIN6 cells. Exendin-4 also inhibited the mitochondrial pathway of apoptosis and down regulated Bax in MIN6 cells. Exendin-4 enhanced glucose-stimulated insulin secretion in the presence of palmitate. Our findings suggest that exendin-4 may prevent lipotoxicity-induced apoptosis in MIN6 cells through activation of PKB and inhibition of the mitochondrial pathway. PMID- 22776330 TI - Unraveling the peptidome of the South African cone snails Conus pictus and Conus natalis. AB - Venoms from cone snails (genus Conus) can be seen as an untapped cocktail of biologically active compounds, being increasingly recognized as an emerging source of peptide-based therapeutics. Cone snails are considered to be specialized predators that have evolved the most sophisticated peptide chemistry and neuropharmacology system for their own biological purposes by producing venoms which contains a structural and functional diversity of neurotoxins. These neurotoxins or conotoxins are often small cysteine-rich peptides which have shown to be highly selective ligands for a wide range of ion channels and receptors. Local habitat conditions have constituted barriers preventing the spreading of Conus species occurring along the coast of South Africa. Due to their scarceness, these species remain, therefore, extremely poorly studied. In this work, the venoms of two South African cone snails, Conus pictus, a vermivorous snail and Conus natalis, a molluscivorous snail, have been characterized in depth. In total, 26 novel peptides were identified. Comparing the venoms of both snails, interesting differences were observed regarding venom composition and molecular characteristics of these components. PMID- 22776331 TI - Gene-environment interactions in Parkinson's disease: specific evidence in humans and mammalian models. AB - Interactions between genetic factors and environmental exposures are thought to be major contributors to the etiology of Parkinson's disease. While such interactions are poorly defined and incompletely understood, recent epidemiological studies have identified specific interactions of potential importance to human PD. In this review, the most current data on gene-environment interactions in PD from human studies are critically discussed. Animal models have also highlighted the importance of genetic susceptibility to toxicant exposure and data of potential relevance to human PD are discussed. Goals and needs for the future of the field are proposed. PMID- 22776332 TI - Sleep disturbance induces neuroinflammation and impairment of learning and memory. AB - Hospitalized patients can develop cognitive function decline, the mechanisms of which remain largely to be determined. Sleep disturbance often occurs in hospitalized patients, and neuroinflammation can induce learning and memory impairment. We therefore set out to determine whether sleep disturbance can induce neuroinflammation and impairment of learning and memory in rodents. Five to 6-month-old wild-type C57BL/6J male mice were used in the studies. The mice were placed in rocking cages for 24 h, and two rolling balls were present in each cage. The mice were tested for learning and memory function using the Fear Conditioning Test one and 7 days post-sleep disturbance. Neuroinflammation in the mouse brain tissues was also determined. Of the Fear Conditioning studies at one day and 7 days after sleep disturbance, twenty-four hour sleep disturbance decreased freezing time in the context test, which assesses hippocampus-dependent learning and memory; but not the tone test, which assesses hippocampus independent learning and memory. Sleep disturbance increased pro-inflammatory cytokine IL-6 levels and induced microglia activation in the mouse hippocampus, but not the cortex. These results suggest that sleep disturbance induces neuroinflammation in the mouse hippocampus, and impairs hippocampus-dependent learning and memory in mice. Pending further studies, these findings suggest that sleep disturbance-induced neuroinflammation and impairment of learning and memory may contribute to the development of cognitive function decline in hospitalized patients. PMID- 22776333 TI - The scaffold protein MEK Partner 1 is required for the survival of estrogen receptor positive breast cancer cells. AB - MEK Partner 1 (MP1 or MAPKSP1) is a scaffold protein that has been reported to function in multiple signaling pathways, including the ERK, PAK and mTORC pathways. Several of these pathways influence the biology of breast cancer, but MP1's functional significance in breast cancer cells has not been investigated. In this report, we demonstrate a requirement for MP1 expression in estrogen receptor (ER) positive breast cancer cells. MP1 is widely expressed in both ER positive and negative breast cancer cell lines, and in non-tumorigenic mammary epithelial cell lines. However, inhibition of its expression using siRNA duplexes resulted in detachment and apoptosis of several ER-positive breast cancer cell lines, but not ER-negative breast cancer cells or non-tumorigenic mammary epithelial cells. Inhibition of MP1 expression in ER-positive MCF-7 cells did not affect ERK activity, but resulted in reduced Akt1 activity and reduced ER expression and activity. Inhibition of ER expression did not result in cell death, suggesting that decreased ER expression is not the cause of cell death. In contrast, pharmacological inhibition of PI3K signaling did induce cell death in MCF-7 cells, and expression of a constitutively active form of Akt1 partially rescued the cell death observed when the MP1 gene was silenced in these cells. Together, these results suggest that MP1 is required for pro-survival signaling from the PI3K/Akt pathway in ER-positive breast cancer cells. PMID- 22776334 TI - "Obama system:" a new easy, safe, and economical technique for laparoscopic single-port surgery. AB - INTRODUCTION: Various approaches to laparoscopic single-site surgery (LESS) have been developed to reduce pain and other complications, promote recovery, and improve cosmetic outcomes, particularly relative to conventional open or laparoscopic surgery. Three-port procedures for LESS have been reported to be superior to single-port access, but they usually require expensive, technically sophisticated instruments. To avoid these problems, we have developed a modified procedure for performing LESS with a single port, referred to as the "Obama system." METHODS: From January 2009 through December 2010, we performed laparoscopic cholecystectomy (LC) in 61 patients. Conventional LC with three ports was performed in 39 patients, LESS with a SILS Port was performed in 4 patients, and modified LESS was performed using the Obama system in 18 patients. The operative results were compared. RESULTS: LC was successfully completed in all 61 patients, with no postoperative complications. The mean operating time was 102.3 min (C-reactive protein [CRP] <= 2) and 160.1 min (CRP > 2) in the 39 patients who underwent conventional LC, 108.3 min (CRP <= 2) in the 4 patients who underwent LESS with a SILS Port, and 116.5 min (CRP <= 2) and 186.5 min (CRP > 2) in the 18 patients who underwent LESS using the Obama system. No morbidity or mortality was associated with any technique. CONCLUSION: The Obama system is easier to use and more efficient and reliable than any other technique currently available for LESS. This system is expected to greatly contribute to the further development and wider acceptance of LESS. PMID- 22776335 TI - Standard of practice on laparoscopic gastric cancer surgery in Korea and Japan: experts' survey. AB - INTRODUCTION: As the laparoscopic approach has become a popular gastric cancer treatment in Korea and Japan, the need for sharing current practices of surgeons who are experienced in laparoscopic gastric cancer surgery has increased. METHODS: We sent a questionnaire on laparoscopic instruments, image documentation, preoperative evaluation, surgical indication, operative methods, and postoperative management to laparoscopic experts in Korea and Japan, and 24 (14 from Korea and 10 from Japan) responded. RESULTS: Endoscopic ultrasound and preoperative endoscopy-guided clipping are routinely employed, respectively, by 14 (58%) and 20 (83%) of the surgeons. Surgeons perform laparoscopy-assisted distal gastrectomy (LADG) based on varying indications. Five surgeons (21%) performed LADG only for cases of stage T1 cancer, 15 (63%) performed LADG on patients with less than T2 lesions, and 4 (17%) performed LADG on patients with less than T3 lesions. With regard to postoperative anastomosis, 18 surgeons (75%) preferred extracorporeal anastomosis and 6 (25%) preferred intracorporeal anastomosis. The mean postoperative hospital stay was 6.5 days in Korea and 10.1 days in Japan (P < 0.001). CONCLUSION: This survey can help to inform the current practice of laparoscopic gastric cancer surgery in Korea and Japan, where laparoscopic surgery is frequently performed. PMID- 22776336 TI - Comparing three different surgical techniques used in adult bilateral varicocele. AB - INTRODUCTION: Varicocele is a common disease in adult men that can be treated with one of several surgical methods. Each technique has advantages and disadvantages, and conflicting results have been obtained by different studies. To evaluate the most effective surgical techniques used in adult bilateral varicocele, including minimally invasive procedures, we compared the outcomes of three common surgical approaches in this prospective randomized study. METHODS: The study included 153 patients with bilateral varicoceles who underwent varicocelectomy. These patients were randomly divided into three equal groups according to surgical approach used - open inguinal, retroperitoneal or laparoscopic. The assessment included operative time, length of hospital stay, clinical outcome and, in cases of infertility, semen analysis. The mean follow-up was 12 months (range, 8 to 15 months). RESULTS: The operative time and hospital stay in the laparoscopic group were significantly shorter than in the other groups (P < 0.01). Of the 51 cases in each group, there were seven cases (13.73%) of recurrence in the open inguinal group, six cases (11.76%) in the retroperitoneal group, and one case (1.96%) in the laparoscopic group. This lower rate of recurrence was statistically significant in the laparoscopic group (P < 0.05). Among the three groups, comparisons between preoperative and postoperative semen parameters showed visible improvements in sperm concentration and motility (P < 0.01), but there were no significant differences between the three groups for postoperative changes in semen parameters (P > 0.05). CONCLUSIONS: Compared with open inguinal and retroperitoneal varicocelectomy, laparoscopic varicolerectomy offers the best outcome. PMID- 22776337 TI - Incidence of complications in patients with benign gynecological diseases by BMI and level of complexity of laparoscopic surgery. AB - INTRODUCTION: Laparoscopic surgery has become a standard surgical method for benign gynecological diseases, but the technique can still be accompanied, albeit infrequently, by intraoperative or postoperative complications. It has been postulated that the frequency of complications differs according to patient body habitus or surgical challenge level. We evaluated the relationship between the complication rate at different levels of surgery and BMI in patients with benign gynecological diseases who have undergone laparoscopic surgery at our hospital. METHODS: A total of 3231 patients who underwent laparoscopic surgery between 1989 and 2010 were enrolled in this study retrospectively. They were classified into four groups by surgery level (diagnostic laparoscopy or minor, major, or advanced laparoscopic surgery). At each challenge level, patients were classified into three groups based on BMI (as defined by the WHO): A group (underweight), BMI < 18.5; B group (healthy), BMI >= 18.5 and < 25; and C group (overweight), BMI >= 25. We compared the complication rates between the groups at each level of surgical challenge. RESULTS: There was no difference in the complication rate between groups A, B and C at any of the surgical challenge levels. However, at the higher surgical difficulty levels, a higher incidence of overall complications was observed. CONCLUSION: The complication rate differs between surgical levels, and complications can occur in any type of surgery, irrespective of the body habitus of the patient. The complication rate is higher when difficult surgical methods are employed, and extra caution is needed. PMID- 22776338 TI - Clinical and safety profiles of bipolar transurethral vaporization of the prostate in saline: a preliminary report. AB - Transurethral vaporization of the prostate in saline (TURisV) is an innovative endoscopic surgical modality for the treatment of benign prostatic hyperplasia (BPH) that vaporizes prostate tissue using a uniquely designed mushroom electrode. TURisV promises instant hemostatic tissue ablation under saline irrigation and offers clinical advantages for endoscopic BPH operations. From July 2008 to February 2009, TURisV was performed in 17 cases with clinically significant BPH. Median operation time was 127.0 min and median volume of vaporized prostate tissue was 41.1 g. Median International Prostate Symptom Score improved from 20 to 4 after 12 months. Median maximum flow rate increased from 5.3 mL/s to 13.8 mL/s after 12 months. Postoperative median residual urine improved from 48.0 mL to 7.0 mL after 12 months. No changes in hemoglobin or electrolyte levels were seen postoperatively. Our results suggest that TURisV is a safe and efficacious treatment for BPH. PMID- 22776339 TI - Laparoscopic resection of a retroperitoneal schwannoma. AB - Herein is a report of a case of a 34-year-old man whose chief complaint was right lower abdominal pain. He was diagnosed with acute appendicitis. Additionally, an abdominal CT scan found retroperitoneal tumor approximately 5 cm in size, with an imaging effect, located adjacent to the dorsal side of the inferior vena cava. For this suspected neurogenic tumor, laparoscopic appendectomy and retroperitoneal tumorectomy were performed after conservative treatment of appendicitis. The retroperitoneal tumor was 5.5 * 3.5 cm in size, had a capsule, smooth surface and soft elasticity, and the divided face was solid white. The histopathological work-up revealed that the tumor was a benign mixed-type schwannoma, in which spindle cells were arranged. The patient's postoperative course was uneventful, and he was discharged from the hospital 7 days after the surgery. In general, retroperitoneal schwannoma is not associated with any symptoms, so it is often discovered accidentally, as in this case. The appropriate treatment for the condition is surgical resection of the tumor including the capsule. However, the use of laparoscopic surgery has been reported in recent years. Although the majority of the cases are benign, there have been some reports of local recurrence. As such, this case will required careful follow ups. PMID- 22776340 TI - Coexistent dermoid cysts of the pouch of the Douglas and ovary resected by laparoscopy. AB - Dermoid cysts of the ovary are one of the most common ovarian neoplasms, but parasitic dermoid cysts as well as coexistent dermoid cysts are unusual. Almost all reports of coexistent dermoid cysts involve the omentum and ovary, but our case involved the pouch of Douglas and ovary. We managed this case by laparoscopy. PMID- 22776341 TI - Minimally invasive removal of a recurrent lumbar herniated nucleus pulposus by the small incised microendoscopic discectomy interlaminar approach. AB - In this report, we introduce two cases of recurrent herniated nucleus pulposus (HNP) at L5-S1 that were successfully removed using the small incised microendoscopic discectomy (sMED) technique, proposed by Dezawa and Sairyo in 2011. sMED was performed via the interlaminar approach with a percutaneous endoscope. The patients had previously underdone microendoscopic discectomy for HNP. For the recurrent HNP, the sMED interlaminar approach was selected because the HNP occurred at the level of L5-S1; the percutaneous endoscopic transforaminal approach was not possible for anatomical reasons. To perform sMED via the interlaminar approach, we employed new, specially made devices to enable us to use this technique. In conclusion, sMED is the most minimally invasive approach available for HNP, and its limitations have been gradually eliminated with the introduction specially made devices. In the near future, percutaneous endoscopic surgery could be the gold standard for minimally invasive disc surgery. PMID- 22776342 TI - Stomach hanging technique using gauze during laparoscopic gastrectomy. AB - INTRODUCTION: Lifting the stomach using laparoscopic instruments during laparoscopic gastrectomy is difficult and increases the risk of crushing the tumor. In this study, we present a stomach hanging technique using gauze pieces that reduces the risk to the tumor. MATERIALS AND SURGICAL TECHNIQUE: After a partial omentectomy and the opening of the lesser sac, the antrum was wrapped with a 15-20-cm gauze piece. Next, a straight needle with 2-0 monofilament suture material pierced the abdominal cavity through the right subcostal area on the mid clavicular line, and the gauze was then sutured twice in a figure of eight manner. The needle was removed percutaneously through the right middle quadrant of the abdomen. Another suture was applied to wrap the left side of the stomach. The stomach was easily lifted and positioned by pulling the four suture strings in different directions. After the suture materials were fastened to the abdominal wall using hemostat forceps, the surgical field was sufficiently exposed, facilitating lymph node dissection on the superior surface of the pancreas. This method freed the assistant from holding the stomach and enabled this individual to assist the operation in other ways. DISCUSSION: This stomach lifting technique using gauze is a good option for exposing the surgical field, enables the assistant to perform other tasks, and reduces the risk of crushing the tumor during laparoscopic gastrectomy. PMID- 22776343 TI - Retroperitoneal approach for laparoscopic nephroureterectomy with stripping technique: extracorporeal ligation of ureter and ureteral catheter. AB - INTRODUCTION: The pluck and stripping techniques are used for lower ureter management in renal pelvic cancer patients. Herein, we report our experience of extracorporeal ligation of the ureter and the ureteral catheter through the trocar port, which differs from conventional laparoscopic ligation in the retroperitoneal space. This technique was selected to reduce the time needed for ureter management using the stripping technique and to provide secure ligation. MATERIALS AND SURGICAL TECHNIQUE: We performed this stripping technique in patients with T1 and T2 stage renal pelvic cancer without imaging-evident lymph node metastasis. After transurethrally placing a ureteral catheter, we resected the circumference of the ureteral orifice. After laparoscopic nephrectomy via a retroperitoneal approach, the ureteral catheter and distal ureter were ligated extracorporeally. The catheter was pulled to invaginate the ureter so it could then be pulled through the external urethral orifice. DISCUSSION: This technique of extracorporeal ligation ensures more a secure ligation of the ureter and ureteral catheter. This modified stripping technique does not require lower ureter management with laparotomy, and it is also useful in shortening the operative time. This method is effective for relatively early stage renal pelvic cancer. PMID- 22776344 TI - Hybrid NOTES colectomy for right-sided colonic tumors. AB - INTRODUCTION: Given the limitation of surgical access and instrumentation, pure NOTES technique currently appears challenging for colorectal surgery. As such, we would like to determine the technical feasibility and clinical results of hybrid NOTES right hemicolectomy with transrectal extraction of specimen. MATERIALS AND SURGICAL TECHNIQUE: After the right-sided colon was fully mobilized and vessels ligated, bowel resection and intracorporeal side-to-side ileocolic anastomosis were performed with endostaplers. The Transanal Endoscopic Operations device was inserted transanally. The resected specimen was removed via the Transanal Endoscopic Operations device through an enterotomy made over the anterior wall of the upper rectum. DISCUSSION: The operation was performed on a 42-year-old woman and lasted 120 minutes; blood loss was 30 mL. The patient had an uneventful recovery and was discharged on postoperative day 5. The median pain score was 2 (range, 2-3). Our preliminary experience shows that hybrid NOTES right hemicolectomy is safe and feasible. The technique eliminates the need for mini laparotomy in patients undergoing laparoscopic right hemicolectomy, and it offers promise in this era of minimally invasive surgery. PMID- 22776345 TI - Transumbilical laparoscopic surgery using GelPort through an umbilical zigzag skin incision. AB - INTRODUCTION: We report herein a new method of transumbilical laparoscopic surgery using a GelPort through an umbilical zigzag skin incision. The method involves collaborating with plastic surgeons to ensure the procedure was minimally invasive. MATERIALS AND SURGICAL TECHNIQUE: After marking a zigzag skin incision in the umbilical region, the skin was incised along this line. Then, a GelPort double-ring wound retractor was inserted through the incision, which enlarged the diameter of the fascial opening to 6 cm. The Gelport was latched on the wound retractor ring, following the inflation of the pneumoperitoneum by CO (2). One or more additional ports were inserted as necessary. All operations were performed in the standard fashion. The specimen was easily extracted from the abdomen through the umbilical incision, and anastomosis was performed. Using the above method, we performed the following procedures: one total gastrectomy, one distal gastrectomy, three gastric local resections, five right hemicolectomies, two high anterior resections, three cholecystectomies, and seven transabdominal preperitoneal hernioplasties. All cases were accomplished without any complications using this method. The wounds of the umbilical region were almost "scarless" in all cases. DISCUSSION: We developed an umbilical zigzag skin incision technique to perform abdominal laparoscopic operations using a GelPort, with a minimal number of skin incisions. We consider that our method reduces the technical difficulties associated with laparoscopic surgery and maintains cosmesis. PMID- 22776346 TI - Long-term clinical outcomes and risk factors for the occurrence of post-operative complications after cardiovascular surgery in patients with Behcet's disease. AB - OBJECTIVES: Cardiovascular surgery in patients with Behcet's disease (BD) frequently leads to postoperative complications such as anastomotic leakage, occlusion or pseudoaneurysm. We evaluated the clinical outcomes and related risk factors of postoperative complications in BD patients undergoing cardiovascular surgeries, as well as the long-term efficiency of postoperative immunosuppressive treatment. METHODS: Forty-one patients with BD who had undergone cardiovascular surgery between 1990 and 2009 were studied. We evaluated the patients' clinical data, postoperative complications, and survival rate. Risk factors related to the occurrence of postoperative complications were identified by univariate analysis using the Kaplan-Meier method with the log-rank test and multivariate analysis using the Cox proportional hazards regression model. RESULTS: Fifty-nine operations were performed in 41 patients. During the mean follow-up period of 65.3+/-48.1 months, complications such as paravalvular leakage, dehiscence, fistula, graft occlusion, or pseudoaneurysm occurred in 29 operations (49.2%). The cumulative occurrence rate of postoperative complication was 10.2% at three months, 32.8% at 12 months, and 43.8% at 24 months. Upon univariate analysis, young age, high Creactive protein levels, lack of postoperative immunosuppression, and short disease duration were identified as significant factors responsible for the occurrence of postoperative complications. In multivariate analysis, postoperative immunosuppression was found to independently lower the risk of complications. The 5-year survival rate was significantly higher in patients with postoperative immunosup immunosuppression than in those without (84.5% vs. 45.0%, p=0.011). CONCLUSIONS: The present study suggests that postoperative immunosuppressive therapy after cardiovascular surgeries in BD patients is important for reducing the development of serious postoperative complications. PMID- 22776347 TI - Cartilage tissue formation from dedifferentiated chondrocytes by codelivery of BMP-2 and SOX-9 genes encoding bicistronic vector. AB - Articular cartilage, when damaged by degenerative disease or trauma, has limited ability for self-repair. Recently, many trials have demonstrated that gene therapy combined with tissue engineering techniques would be a promising approach for cartilage regeneration. Bone morphogenetic protein 2 (BMP-2) is an important signal for upregulation of osteogenesis and chondrogenesis of stem cells. Sex determining region Y box gene 9 (SOX-9) has also been reported as one of the key transcription factors for chondrogenesis. We hypothesized that codelivery of BMP 2 and SOX-9 genes would result in improved efficiency of recovery of normal chondrogenic properties in dedifferentiated chondrocytes. To this aim, we constructed a bicistronic vector encoding the BMP-2 and SOX-9 genes linked to the "self-cleaving" 2A peptide sequence. After gene delivery to dedifferentiated chondrocytes using a microporator transfection system, we confirmed over 65% delivery efficiency of the BMP-2 and SOX-9 genes. According to RT-PCR analysis and Alcian blue staining, simultaneous delivery of BMP-2/SOX-9 resulted in significantly increased expression of chondrogenesis-related markers (type II collagen and aggrecan) and GAG matrix formation compared with individual delivery of the BMP-2 or SOX-9 gene. Six weeks after in vivo transplantation, BMP-2/SOX-9 genes also showed a significant increase in cartilage formation compared with the BMP-2 or SOX-9 gene. These results demonstrate that codelivery of two chondrogenic lineage-determining genes can enhance normal chondrogenic properties of dedifferentiated chondrocytes followed by improved cartilage formation. PMID- 22776348 TI - A group-theoretical notation for disease states: an example using the psychiatric rating scale. AB - BACKGROUND: While many branches of natural science have embraced group theory reaping enormous advantages for their respective fields, clinical medicine lacks to date such applications. Here we intend to explain a prototypal model based on the postulates of groups that could have potential in categorizing clinical states. METHOD: As an example, we begin by modifying the original 'Brief Psychiatric Rating Scale' (BPRS), the most frequently used standards for evaluating the psychopathology of patients with schizophrenia. We consider a presumptively idealized (virtually standardized) BPRS (denoted BPRS-I) with assessments ranging from '0' to '6' to simplify our discussion. Next, we introduce the modulo group Z7 containing elements {0,1,2,...,6} defined by composition rule, 'modulo 7 addition', denoted by *. Each element corresponds to a score resulting from grading a symptom under the BPRS-I assessment. By grading all symptoms associated with the illness, a Cartesian product, denoted Aj, constitutes a summary of a patient assessment. By considering operations denoted A(j->k) that change state Aj into state Ak, a group M (that itself contains Aj and Ak as elements) is also considered. Furthermore, composition of these operations obey modulo 7 arithmetic (i.e., addition, multiplication, and division). We demonstrate the application with a simple example in the form of a series of states (A4 = A1*A(1->2)*A(2->3)*A(3->4)) to illustrate this result. RESULTS: The psychiatric disease states are defined as 18-fold Cartesian products of Z7, i.e., Z7*18 = Z7*...*Z7 (18 times). We can construct set G = {a(m)i| m = 1,2,3,...(the patient's history of the i-th symptom)} and M = {Am | Am ? Z7*18 (the set of all possible assessments of a patient)} simplistically, at least, in terms of modulo 7 addition that satisfies the group postulates. CONCLUSIONS: Despite the large limitations of our methodology, there are grounds not only within psychiatry but also within other medical fields to consider more generalized notions based on groups (if not rings and fields). These might enable through some graduated expression a systematization of medical states and of medical procedures in a manner more aligned with other branches of natural science. PMID- 22776349 TI - Cannabinoids: a new hope for breast cancer therapy? AB - Breast cancer is a very common disease that affects approximately 1 in 10 women at some point in their lives. Importantly, breast cancer cannot be considered a single disease as it is characterized by distinct pathological and molecular subtypes that are treated with different therapies and have diverse clinical outcomes. Although some highly successful treatments have been developed, certain breast tumors are resistant to conventional therapies and a considerable number of them relapse. Therefore, new strategies are urgently needed, and the challenge for the future will most likely be the development of individualized therapies that specifically target each patient's tumor. Experimental evidence accumulated during the last decade supports that cannabinoids, the active components of Cannabis sativa and their derivatives, possess anticancer activity. Thus, these compounds exert anti-proliferative, pro-apoptotic, anti-migratory and anti invasive actions in a wide spectrum of cancer cells in culture. Moreover, tumor growth, angiogenesis and metastasis are hampered by cannabinoids in xenograft based and genetically-engineered mouse models of cancer. This review summarizes our current knowledge on the anti-tumor potential of cannabinoids in breast cancer, which suggests that cannabinoid-based medicines may be useful for the treatment of most breast tumor subtypes. PMID- 22776350 TI - Seasonal photosynthetic responses of European oaks to drought and elevated daytime temperature. AB - Oaks are commonly considered as drought- and heat-tolerant trees that might benefit from a warmer and drier climate. Their tolerance to drought has been frequently studied in the past, whereas studies dealing with elevated temperature or its combination with drought are very limited in number. In this study we investigated seasonal photosynthetic patterns in three European oak species (Quercus robur, Q. petraea, Q. pubescens) exposed in lysimeter-based open-top chambers (OTC) to elevated daytime temperature, drought and their combination. Stomatal and non-stomatal traits of photosynthesis were followed over an entire growing season and related to changes in daytime temperature, soil moisture and pre-dawn leaf water potential (Psi(PD) ). Elevated daytime temperature enhanced net photosynthesis (P(N) ) in a season-dependent manner, with higher mid-summer rates than in controls exposed to ambient temperature. Drought imposed in early and mid-summer reduced the soil moisture content and caused a gradual decline in Psi(PD) , stomatal conductance (g(S) ) and P(N) . Drought effects on Psi(PD) and P(N) were exacerbated when drought was combined with elevated daytime temperature. In general, P(N) tended to be more affected by low soil moisture content or low Psi(PD) in Q. robur than in Q. petraea and Q. pubescens. Non stomatal limitations may have contributed to the drought-induced decline of P(N) in Q. robur, as indicated by a down-regulation of PSII photochemistry (F(V) /F(M) ) and decreased chlorophyll content. Taken together, our findings show that European oaks may benefit from elevated temperature, but detrimental effects can be expected when elevated temperature occurs simultaneously with drought. PMID- 22776351 TI - Perioperative outcomes of severely obese children undergoing tonsillectomy. AB - BACKGROUND: Sleep-disordered breathing, a common condition in obese children, is a frequent indication for tonsillectomy. OBJECTIVE: The purpose of this study was to examine the association between obesity and perioperative complications in children undergoing tonsillectomy. METHODS/MATERIALS: A sample of 100 severely obese children (body mass index for age [BMIA], >= 98 th percentile) between ages 2 and 18 years who underwent tonsillectomy at Mayo Clinic Rochester was randomly selected. Each severely obese child was age (+/- 2 years) and sex matched to two normal weight children (BMIA between 25th and 75th percentiles) undergoing tonsillectomy during the study period, and their medical records were reviewed. RESULTS: Severely obese children had a significantly higher incidence of comorbid conditions including respiratory disorders and severe systemic disorders or syndromes. Severely obese children had a higher frequency of perioperative airway complications (15.0% vs 2.0%). From posthoc analyses, severe obesity remained a significant risk factor for perioperative adverse events after adjusting for the presence of severe systemic disorders or syndromes (OR 8.8; 95% CI 2.8-27.5, P < 0.001) and also after adjusting for preoperative respiratory disorders (OR 7.7; 95% CI 2.5-24.3, P < 0.001). When children with planned admissions were excluded from the analysis, severe obesity was associated with an increased rate of unplanned hospital admission (OR 3.80, 95% CI 1.8-7.9, P < 0.001). CONCLUSIONS: Severe obesity in children undergoing tonsillectomy is independently associated with an increased risk of perioperative complications. It appears that both severe obesity and systemic comorbid condition contribute to higher proportions of inpatient tonsillectomies performed in our institution. PMID- 22776352 TI - Evaluating components of dental care utilization among adults with diabetes and matched controls via hurdle models. AB - BACKGROUND: About one-third of adults with diabetes have severe oral complications. However, limited previous research has investigated dental care utilization associated with diabetes. This project had two purposes: to develop a methodology to estimate dental care utilization using claims data and to use this methodology to compare utilization of dental care between adults with and without diabetes. METHODS: Data included secondary enrollment and demographic data from Washington Dental Service (WDS) and Group Health Cooperative (GH), clinical data from GH, and dental-utilization data from WDS claims during 2002-2006. Dental and medical records from WDS and GH were linked for enrollees continuously and dually insured during the study. We employed hurdle models in a quasi-experimental setting to assess differences between adults with and without diabetes in 5-year cumulative utilization of dental services. Propensity score matching adjusted for differences in baseline covariates between the two groups. RESULTS: We found that adults with diabetes had lower odds of visiting a dentist (OR = 0.74, p < 0.001). Among those with a dental visit, diabetes patients had lower odds of receiving prophylaxis (OR = 0.77), fillings (OR = 0.80) and crowns (OR = 0.84) (p < 0.005 for all) and higher odds of receiving periodontal maintenance (OR = 1.24), non surgical periodontal procedures (OR = 1.30), extractions (OR = 1.38) and removable prosthetics (OR = 1.36) (p < 0.001 for all). CONCLUSIONS: Patients with diabetes are less likely to use dental services. Those who do are less likely to use preventive care and more likely to receive periodontal care and tooth extractions. Future research should address the possible effectiveness of additional prevention in reducing subsequent severe oral disease in patients with diabetes. PMID- 22776353 TI - Rapid identification of Leishmania spp. in formalin-fixed, paraffin-embedded tissue samples by fluorescence in situ hybridization. AB - OBJECTIVE: To describe and validate fluorescence in situ hybridization (FISH), a new method of Leishmania spp. identification. FISH allows for a rapid detection of target organisms by specific binding of fluorescently labelled oligonucleotide probes to ribosomal RNA. METHODS: Two genus-specific, fluorescently labelled Leishmania spp. FISH probes were designed and evaluated with a panel of 18 Leishmania spp. and six Trypanosoma spp. including well-defined strains and clinical isolates. In addition, the FISH probes were tested in comparison with Giemsa staining in formalin-fixed, paraffin-embedded tissues of five mice that had been artificially infected with Leishmania major strains, leading to concordant results. Finally, 11 tissue samples of patients with cutaneous leishmaniasis, four tissue samples of patients with visceral leishmaniasis, and one native bone marrow sample of a patient with visceral leishmaniasis were analysed with FISH and Giemsa staining. RESULTS: Concordant results were achieved by FISH and Giemsa staining in 15/16 specimens. CONCLUSION: This analysis provides proof of principle that FISH is a suitable method for the rapid and easy detection of Leishmania spp. in formalin-fixed, paraffin-embedded tissue samples. Because of the good contrast of Leishmania spp. in tissue, FISH facilitates the identification of these organisms in tissue samples even by less experienced investigators. PMID- 22776354 TI - CHILDHOOD DEPRESSION. Exploring the association between family violence and other psychosocial factors in low-income Brazilian schoolchildren. AB - BACKGROUND: Childhood depression affects the morbidity, mortality and life functions of children. Individual, family and environmental factors have been documented as psychosocial risk factors for childhood depression, especially family violence, which results in inadequate support, low family cohesion and poor communication. This study investigates the association between psychosocial depression factors in low-income schoolchildren and reveals the potential trouble spots, highlighting several forms of violence that take place within the family context. METHODS: The study was based on a cross-sectional analysis of 464 schoolchildren aged between 6 and 10, selected by random sampling from a city in the state of Rio de Janeiro, Brazil. Socio-economic, family and individual variables were investigated on the strength of the caregivers' information and organized in blocks for analysis. A binary logistic regression model was applied, according to hierarchical blocks. RESULTS: The final hierarchical regression analysis showed that the following variables are potential psychosocial factors associated with depression in childhood: average/poor relationship with the father (OR 3.24, 95% CI 1.32-7.94), high frequency of victimization by psychological violence (humiliation) (OR 6.13, 95% CI 2.06-18.31), parental divorce (OR 2.89, 95% CI 1.14-7.32) and externalizing behavior problems (OR 3.53 IC 1.51-8.23). CONCLUSIONS: The results point to multiple determinants of depressive behavior in children, as well as the potential contribution of psychological family violence. The study also reveals potential key targets for early intervention, especially for children from highly vulnerable families. PMID- 22776355 TI - Bacteroides thetaiotaomicron VPI-5482 glycoside hydrolase family 66 homolog catalyzes dextranolytic and cyclization reactions. AB - Bacteroides thetaiotaomicron VPI-5482 harbors a gene encoding a putative cycloisomaltooligosaccharide glucanotransferase (BT3087) belonging to glycoside hydrolase family 66. The goal of the present study was to characterize the catalytic properties of this enzyme. Therefore, we expressed BT3087 (recombinant endo-dextranase from Bacteroides thetaiotaomicron VPI-5482) in Escherichia coli and determined that recombinant endo-dextranase from Bacteroides thetaiotaomicron VPI-5482 preferentially synthesized isomaltotetraose and isomaltooligosaccharides (degree of polymerization > 4) from dextran. The enzyme also generated large cyclic isomaltooligosaccharides early in the reaction. We conclude that members of the glycoside hydrolase 66 family may be classified into three types: (a) endo dextranases, (b) dextranases possessing weak cycloisomaltooligosaccharide glucanotransferase activity, and (c) cycloisomaltooligosaccharide glucanotransferases. PMID- 22776357 TI - F-actin accumulates in the vulva of female Strongyloides venezuelensis. AB - Little is known about the actin cytoskeleton architecture in female Strongyloides venezuelensis and thus to investigate the distribution and concentration of actin, female worms were labelled with phalloidin-rhodamine and visualized under confocal microscopy. Our results demonstrate that filamentous actin accumulates in the vulva and the concentration of F-actin at this site suggests its important role, especially during oviposition, in the life cycle of S. venezuelensis. PMID- 22776358 TI - Anorectal function after partial intersphincteric resection in ultra-low rectal cancer. AB - AIM: To investigate the feasibility and efficacy of intersphincteric resection (ISR), in terms of postoperative anorectal function, for ultra-low rectal cancer in mainland China. METHOD: A total of 43 patients who consecutively underwent curative partial ISR for ultra-low rectal cancer between 2006 and 2009 were enrolled in the study. Defaecatory function was assessed, using detailed questionnaires, 3, 6 and 12 months after surgery. The Wexner score was used to assess faecal continence, and anal manometry studies were performed to analyse anal sphincter function. RESULTS: Overall defaecatory function was assessed as being satisfactory in 41 of 43 patients. Twelve months after surgery, the mean Wexner score was 4.0 +/- 3.6. Anal manometry studies showed a significant change at 3 months and further, gradual, improvement over the following year. During the postoperative period, maximum squeeze pressure reached a normal value of 174.1 +/ 19.5 mmHg (P = 0.041) by 6 months and resting pressure was 42.4 +/- 5.6 mmHg by 12 months, which was close to the preoperative level (P = 0.038). CONCLUSION: Because of the satisfactory recovery of defaecatory function and good oncological results, partial ISR may be recommended as an effective sphincter-preserving operation for patients with ultra-low rectal cancer. PMID- 22776359 TI - Potential impact of curcumin and taurine on human hepatoma cells using Huh-7 cell line. AB - OBJECTIVES: This study aimed at exploring the role of curcumin and taurine alone or in combination against cultured human hepatoma cells (Huh-7 cells). DESIGN AND METHODS: Huh-7 cells were plated and treated with various concentrations of curcumin and/or taurine. Hemocytometer cell count, cell viability, quantification of gamma-IFN concentrations, and flow cytometric analyses for CD4, CD8, and CD25 were carried out. RESULTS: There were significant increases in the levels of cell density, gamma-IFN, and CD8, accompanied with significant decrease in the level of CD4, when comparing cultured cells treated with curcumin and taurine with control cultured cells. CONCLUSION: Curcumin/taurine in combination formula is better treatment than single therapy, with respect to cell density and gamma-IFN. Moreover, curcumin/taurine combined therapy enhances immunity by stimulating the CD4(+) T-helper cells with consequent induction of CD8 T-cell responses to lyse tumor cells. PMID- 22776356 TI - Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia. AB - BACKGROUND: Mitochondrial dysfunction is one of the major events responsible for activation of neuronal cell death pathways during cerebral ischemia. Trace element selenium has been shown to protect neurons in various diseases conditions. Present study is conducted to demonstrate that selenium preserves mitochondrial functional performance, activates mitochondrial biogenesis and prevents hypoxic/ischemic cell damage. RESULTS: The study conducted on HT22 cells exposed to glutamate or hypoxia and mice subjected to 60-min focal cerebral ischemia revealed that selenium (100 nM) pretreatment (24 h) significantly attenuated cell death induced by either glutamate toxicity or hypoxia. The protective effects were associated with reduction of glutamate and hypoxia induced ROS production and alleviation of hypoxia-induced suppression of mitochondrial respiratory complex activities. The animal studies demonstrated that selenite pretreatment (0.2 mg/kg i.p. once a day for 7 days) ameliorated cerebral infarct volume and reduced DNA oxidation. Furthermore, selenite increased protein levels of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) and nuclear respiratory factor 1 (NRF1), two key nuclear factors that regulate mitochondrial biogenesis. Finally, selenite normalized the ischemia-induced activation of Beclin 1 and microtubule-associated protein 1 light chain 3-II (LC3-II), markers for autophagy. CONCLUSIONS: These results suggest that selenium protects neurons against hypoxic/ischemic damage by reducing oxidative stress, restoring mitochondrial functional activities and stimulating mitochondrial biogenesis. PMID- 22776360 TI - Iron and holotransferrin induce cAMP-dependent differentiation of Schwann cells. AB - The differentiation of myelin-forming Schwann cells (SC) is completed with the appearance of myelin proteins MBP and P(0) and a concomitant downregulation of markers GFAP and p75NTR, which are expressed by immature and adult non-myelin forming SC. We have previously demonstrated that holotransferrin (hTf) can prevent SC dedifferentiation in culture (Salis et al., 2002), while apotransferrin (aTf) cannot. As a consequence, we used pure cultured SC and submitted them to serum deprivation in order to promote dedifferentiation and evaluate the prodifferentiating ability of ferric ammonium citrate (FAC) through the expression of MBP, P(0), p75NTR and c-myc. The levels of cAMP, CREB and p CREB were also measured. Results show that Fe(3+), either in its free form or as hTf, can prevent the dedifferentiation promoted by serum withdrawal. Both FAC and hTf were proven to promote differentiation, probably through the increase in cAMP levels and CREB phosphorylation, as well as levels of reactive oxygen species. This effect was inhibited by deferroxamine (Dfx, an iron chelator), H9 (a cAMP PKA antagonist) and N-acetylcysteine (NAC, a powerful antioxidant). PMID- 22776361 TI - The ASP3 locus in Saccharomyces cerevisiae originated by horizontal gene transfer from Wickerhamomyces. AB - The asparagine degradation pathway in the S288c laboratory strain of Saccharomyces cerevisiae is comprised of genes located at two separate loci. ASP1 is located on chromosome IV and encodes for cytosolic l-asparaginase I, whereas ASP3 contains a gene cluster located on chromosome XII comprised of four identical genes, ASP3-1, ASP3-2, ASP3-3, and ASP3-4, which encode for cell wall associated l-asparaginase II. Interestingly, the ASP3 locus appears to be only present, in variable copy number, in S. cerevisiae strains isolated from laboratory or industrial environments and is completely absent from the genomes of 128 diverse fungal species. Investigation of the evolutionary history of ASP3 across these 128 genomes as well as across the genomes of 43 S. cerevisiae strains shows that ASP3 likely arose in a S. cerevisiae strain via horizontal gene transfer (HGT) from, or a close relative of, the wine yeast Wickerhamomyces anomalus, which co-occurs with S. cerevisiae in several biotechnological processes. Thus, because the ASP3 present in the S288c laboratory strain of S. cerevisiae is induced in response to nitrogen starvation, its acquisition may have aided yeast adaptation to artificial environments. Our finding that the ASP3 locus in S. cerevisiae originated via HGT further highlights the importance of gene sharing between yeasts in the evolution of their remarkable metabolic diversity. PMID- 22776362 TI - Chromosome conformation capture assays in bacteria. AB - Bacterial chromosomes must be compacted by three-orders of magnitude to fit within the cell. While such compaction could in theory yield disordered structures, it is becoming increasingly clear that bacterial chromosomes are in fact arranged in regular and reproducible fashions and that their configurations are tightly connected to fundamental processes such as chromosome segregation. Nonetheless, due to throughput and resolution limitations associated with traditional assays, many question regarding bacterial chromosome structure and its relation to genome function remain. Here, I review the related technologies, chromosome conformation capture (3C) and chromosome conformation capture carbon copy (5C), which my collaborators and I recently introduced as tools to probe the high-resolution folding of entire bacterial genomes. These technologies utilize covalent cross-linking and proximity ligation to facilitate the measurement of the spatial positioning of hundreds of genomic loci, thereby opening the door to high-throughput studies of bacterial chromosome structure. Hence, 3C and 5C represent powerful new tools for assaying the three-dimensional architecture of bacterial genomes. PMID- 22776364 TI - Clinical outcomes of laparoscopic adhesiolysis for mechanical small bowel obstruction. AB - INTRODUCTION: Laparoscopy for small bowel obstruction (SBO) has increasingly been performed for the advantages minimally invasive surgery provides. However, its benefit remains unclear. METHODS: From January 2004 to July 2011, we enrolled 28 consecutive patients who underwent a laparoscopic operation for SBO, secondary to postoperative adhesions. We compared the results of SBO patients treated laparoscopically with those of 25 patients who underwent conventional open laparotomy in a retrospective matched-pair analysis. RESULTS: Laparoscopic treatment was completed in 25 patients (89%), including 17 laparoscopic-assisted cases. The mean procedural time was 112 minutes in the laparoscopic group and 79 minutes in the open group (P < 0.05). Patients resumed oral intake after a mean of 3 days in the laparoscopic group compared with a mean of 6.5 days in the open group (P < 0.05). The length of hospital stay was 11 and 22 days (P < 0.05), respectively, in the laparoscopic and open groups. Postoperative complications occurred in two patients in the laparoscopy group and 14 patients in the open group (P < 0.05). CONCLUSION: The laparoscopic approach was effective for the management of mechanical SBO in selected patients. Furthermore, minimally invasive laparoscopic adhesiolysis is also feasible and brings the benefit of cosmetic results. PMID- 22776363 TI - A genome-wide 3C-method for characterizing the three-dimensional architectures of genomes. AB - Accumulating evidence demonstrates that the three-dimensional (3D) organization of chromosomes within the eukaryotic nucleus reflects and influences genomic activities, including transcription, DNA replication, recombination and DNA repair. In order to uncover structure-function relationships, it is necessary first to understand the principles underlying the folding and the 3D arrangement of chromosomes. Chromosome conformation capture (3C) provides a powerful tool for detecting interactions within and between chromosomes. A high throughput derivative of 3C, chromosome conformation capture on chip (4C), executes a genome wide interrogation of interaction partners for a given locus. We recently developed a new method, a derivative of 3C and 4C, which, similar to Hi-C, is capable of comprehensively identifying long-range chromosome interactions throughout a genome in an unbiased fashion. Hence, our method can be applied to decipher the 3D architectures of genomes. Here, we provide a detailed protocol for this method. PMID- 22776365 TI - Intraoperative colonoscopy facilitates safe dissection of the rectal pouch in a case of male imperforate anus. AB - INTRODUCTION: In an imperforate anus, colostography often fails to identify recto urethral fistula (RUF). Thus, surgeons must always assume an RUF is present, despite colostography findings, and dissect the distal rectal pouch (RP) with caution. We report the usefulness of intraoperative colonoscopy (IOC) for excluding RUF and, thus, facilitating safe dissection of the RP. METHODS: We used IOC in six cases of imperforate anus. All had right transverse colostomy initially after birth. Distal colostography excluded RUF in five cases and was inconclusive in one. Laparoscopy was used to free the RP carefully from the bladder neck in all cases. Near the prostate, a 4-mm fine, flexible colonoscope was inserted into the RP through the anterior rectal wall to observe the laparoscopic dissection of the RP, which was attached closely to the prostate/bulbar urethra intraluminally to prevent injury to the urethra. The mucosa of the distal end of the RP was mucosectomized or diathermied, and the colon was pulled-through. Mean age at surgery was 11 months. RESULTS: IOC excluded RUF under direct vision in all cases, which enabled the dissection of the RP to be monitored and to proceed smoothly. At follow-up (mean: 31 months), all cases were well. CONCLUSIONS: IOC can be used to exclude RUF and facilitate safe dissection of the RP in imperforate anus. PMID- 22776366 TI - Laparoscopic splenectomy using pneumoperitoneum or gasless abdominal wall lifting: a 15-year single institution experience. AB - INTRODUCTION: Laparoscopic splenectomy using pneumoperitoneum has been performed since 1992. The gasless abdominal wall-lifting method for laparoscopic splenectomy was introduced as an alternative. This retrospective study was undertaken to compare results using the two techniques. METHODS: Between 1995 and 2010, 54 patients underwent laparoscopic splenectomy at a single institution; 30 underwent the procedure using the gasless technique and 24 using pneumoperitoneum. There were no significant differences between the two groups regarding age, sex or BMI, but more patients underwent concurrent operations in the pneumoperitoneum group. The abdominal wall-lift system with subcutaneous K wires was used for the gasless method. RESULTS: Intraoperative blood loss was similar in the two groups (193.0 +/- 196.7 mL gasless, 217.3 +/- 296.6 mL pneumoperitoneum; P > 0.05), but operative time (182.1 +/- 92.1 min, 135.1 +/- 46.1 min; P < 0.05), and resected spleen weight (306.1 +/- 297.7 g, 138 +/- 81.0 g; P < 0.05) were significantly different. In the gasless group, additional procedures included conversion (n = 1), mini-laparotomy (n = 2), and CO(2) insufflation (n = 2). Excluding the concurrent living-related kidney donor patients, hospital stay was similar (6.9 +/- 2.5 days, 6.3 +/- 2.0 days, P > 0.05). CONCLUSION: Although gasless laparoscopic splenectomy is feasible, there are disadvantages, particularly the restricted operative working space in some patients. These results suggest that either technique may be used on an individual basis in patients undergoing laparoscopic splenectomy. PMID- 22776367 TI - Unanticipated troubles in video-assisted thoracic surgery: a proposal for the classification of troubleshooting. AB - INTRODUCTION: Most thoracic surgeons encounter atypical cases or unexpected situations that usually lead them to convert minimally invasive surgery to open thoracotomy. But are there other options besides open surgery? The purpose of this study was to suggest a video-assisted thoracic surgery (VATS) classification system and present tips for the application of VATS to atypical cases or unexpected situations. We have categorized VATS procedures for atypical cases or unexpected situations into two groups: the modification of techniques/instruments and the creation of additional access incisions. METHODS: We retrospectively reviewed VATS with optional additional techniques. We used direct visualization or monitoring as the situation demanded, switching back and forth between the monitor and direct vision. RESULTS: Of the 33 cases we reviewed, 27 patients had malignant lung disease and 6 had benign lung disease. All patients underwent lobectomies including one or more of the following: bronchoplasty (n = 12), control of the main pulmonary artery (n = 9), total adhesiotomy (n = 7), combined resection with the diaphragm (n = 3), and separation of totally fused fissures (n = 2). The mean length of the skin incision was 8 cm, the mean total operating time was 208 min, and the mean blood loss was 173 mL No operative or hospital deaths occurred. CONCLUSIONS: Veteran surgeons can instinctively deal with intraoperative variance, but we frequently see inexperienced surgeons panic and change the course of their procedures. A VATS classification system may have educational benefits for newer surgeons. We believe that the creation of a categorized coping plan will help inexperienced surgeons deal with unanticipated problems. PMID- 22776368 TI - Percutaneous drainage of gastric remnant dilatation after laparoscopic Roux-en-Y gastric bypass. AB - Roux-en-Y gastric bypass is a commonly performed bariatric procedure worldwide. Gastric remnant dilatation is an uncommon early complication of this procedure that can be fatal if treatment is delayed, as it can cause peritonitis and death. Herein we report a gastric bypass patient who presented with profound shock 3 months after the surgery. After resuscitation and evaluation, she was diagnosed as having a massive dilatation of gastric remnant, which we managed with percutaneous drainage. PMID- 22776369 TI - Successful treatment of duodenal carcinoid tumor by laparoscopy-assisted endoscopic full-thickness resection with lymphadenectomy. AB - Reports on endoscopic full-thickness resection of the duodenum using the endoscopic submucosal dissection technique are rare. Here we present a case of a duodenal bulb carcinoid tumor successfully treated by laparoscopy-assisted endoscopic full-thickness resection (LAEFR). An asymptomatic 65-year-old woman had a 10-mm, submucosal tumor on the anterior wall of the duodenal bulb. Abdominal CT revealed an enlarged lymph node adjacent to the duodenum and pancreas. Although we informed the patient of the need for pancreatoduodenectomy with a lymphadenectomy, the patient expressly requested LAEFR. After negative nodal metastasis was confirmed by an intraoperative frozen section of the enlarged nodes, LAEFR was performed using the endoscopic submucosal dissection technique under the laparoscopic assistance. The duodenal wall defect was closed by laparoscopy with an Albert anastomosis. The entire circumferential margin of the specimen was histopathologically negative for carcinoid tumor cells. In summary, LAEFR enables en bloc and whole-layer excision of nonperiampullary duodenal lesions with a sufficient surgical margin, both vertically and laterally. LAEFR is a minimally invasive and effective treatment for selected patients with duodenal carcinoid tumor. PMID- 22776370 TI - Pneumothorax following endoscopic submucosal dissection of a rectal tumor. AB - Endoscopic submucosal dissection is a useful alternative to endoscopic mucosal resection and surgery for en bloc resection of colorectal tumors. However, the technique is considered to be difficult, and potential complications include perforation and postoperative bleeding. In this case report, we present a case of a 63-year-old woman who developed pneumothorax after endoscopic submucosal dissection of a rectal tumor. PMID- 22776371 TI - Thoracic empyema due to migrated endoclips after laparoscopic cholecystectomy. AB - We describe the case of a patient who developed right thoracic empyema 1 year after laparoscopic cholecystectomy. The patient experienced right chest pain and swelling; radiography and CT showed an intrathoracic abscess penetrating the extrathoracic space and the presence of metal clips over the diaphragm. After drainage of the subcutaneous abscess, fluid accumulation decreased; bacterial examination showed no positive findings. Another year later, the patient's condition relapsed. We thought that the empyema may have been caused by endoclips that had migrated. We performed thoracoplasty and retrieved three endoclips from the intrathoracic empyema cavity. The patient showed good recovery after the operation. PMID- 22776372 TI - Case of thoracoscopic right upper lobectomy for lung cancer with tracheal bronchus and a pulmonary vein variation. AB - A 58-year-old woman visited our hospital with the chief complaint of an abnormal chest shadow. Chest CT showed an 18-mm ground-glass opacity in the right upper lobe, which became enlarged over time, and lung cancer was suspected. At the same time, a tracheal bronchus originating directly from the trachea was observed. She underwent thoracoscopic right upper lobectomy and mediastinal lymph node dissection. During surgery, in addition to the tracheal bronchus, a pulmonary vein variation was seen running dorsal to the pulmonary artery. Her postoperative course was uneventful. Tracheal bronchus is a rare anomaly, with an incidence of 0.1%-5%. Since tracheal bronchus is often accompanied by pulmonary vessel variations and may be associated with repeated previous infections, care should be taken when performing thoracoscopic lung resection. PMID- 22776373 TI - Lung cancer associated with an azygos lobe successfully treated with video assisted thoracoscopic surgery. AB - Primary lung cancer associated with an azygos lobe is extremely rare. Herein, we report the case of a 64-year-old woman with lung adenocarcinoma arising in the right upper lobe with an azygos lobe. The patient underwent a right upper lobectomy and lymph node dissection with video-assisted thoracoscopic surgery. Video-assisted thoracoscopic surgery lobectomy for lung cancer of this variant has yet to be reported. We demonstrate the intraoperative findings and the resected pulmonary lobe. This is the first case of primary lung cancer associated with the azygos lobe treated by lobectomy with video-assisted thoracoscopic surgery. PMID- 22776374 TI - Laparoendoscopic single-site surgery for urachal remnants. AB - INTRODUCTION: Urachal remnants are relatively rare but may potentially cause various symptoms and an increased risk for developing adenocarcinoma. Open or laparoscopic surgery is usually used for their resection. Laparoendoscopic single site surgery has been recently applied in several surgical procedures. This report describes two cases of vesicourachal diverticulum treated by resection using laparoendoscopic single-site surgery. MATERIALS AND SURGICAL TECHNIQUE: In each case, laparoendoscopic single-site surgery was performed transperitoneally via one port at a subumbilical semicircular incision. Except for a flexible camera and SILS Port, traditional, non-flexible laparoscopic instruments were used. After the induction of general anesthesia, the patient was placed in a supine position (or lithotomy position). A 2.0-cm incision was made semicircumferentially following the natural subumbilical folds. After the umbilical ligament was cut under direct vision, a SILS Port was placed at the incision. The urachus was liberated distally down to the roof of the urinary bladder using 0 degrees 5-mm flexible camera. Vesicourachal diverticulum with a bladder cuff was completely excised under the supporting view of cystoscopy. Both patients' perioperative days were uneventful. DISCUSSION: Our findings suggest that the laparoendoscopic single-site surgery procedure is safe, minimally invasive and cosmetically acceptable. Therefore, this procedure is an excellent option for the radical resection of urachal remnants. PMID- 22776375 TI - Effects of wet heat treatment on the germination of individual spores of Clostridium perfringens. AB - AIM: To analyse the effect of wet heat treatment on nutrient and non-nutrient germination of individual spores of Clostridium perfringens. METHODS AND RESULTS: Raman spectroscopy and differential interference contrast (DIC) microscopy were used to monitor the dynamic germination of individual untreated and wet heat treated spores of Cl. perfringens with various germinants. When incubated in water at 90-100 degrees C for 10-30 min, more than 90% of spores were inactivated but 50-80% retained their Ca(2+) -dipicolinic acid (CaDPA). The wet heat-treated spores that lost CaDPA exhibited extensive protein denaturation as seen in the 1640-1680 cm(-1) (amide I) and 1230-1340 cm(-1) (amide III) regions of Raman spectra, while spores that retained CaDPA showed partial protein denaturation. Wet heat-treated spores that retained CaDPA germinated with KCl or l-asparagine, but wet heat treatment increased values of T(lag) , DeltaT(release) and DeltaT(lys) , during which spores initiated release of the majority of their CaDPA after mixing with germinant, released >90% of their CaDPA and completed the decrease in their DIC intensity because of cortex hydrolysis, respectively. Untreated Cl. perfringens spores lacking the essential cortex-lytic enzyme (CLE), SleC, exhibited longer T(lag) and DeltaT(release) values during KCl germination than wild-type spores and germinated poorly with CaDPA. Wet heat-treated wild type spores germinating with CaDPA or dodecylamine exhibited increased T(lag) , DeltaT(release) and DeltaT(lys) values, as did wet heat-treated sleC spores germinating with dodecylamine. CONCLUSIONS: (i) Some proteins important in Cl. perfringens spore germination are damaged by wet heat treatment; (ii) the CLE SleC or the serine protease CspB that activates SleC might be germination proteins damaged by wet heat; and (iii) the CaDPA release process seems likely to be damaged by wet heat. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides information on the germination of individual Cl. perfringens spores and improves the understanding of effects of wet heat treatment on spores. PMID- 22776376 TI - Development and validation of a fast HPLC/photodiode array detection method for the measurement of voriconazole in human serum samples. A reference laboratory experience. AB - The aim of this study was the development and validation of a fast and simple high performance liquid chromatography method for measuring voriconazole in human serum using ravuconazole as an external standard. The experience of the reference laboratory in therapeutic drug monitoring of voriconazole is also reported. This method is based on the precipitation of proteins in human serum and detection by HPLC/UV. Chromatographic separation is achieved using an isocratic solvent delivery with detection at 255 nm and a run time of 7 min. The assay was validated according to international guidelines and was also applied to the analysis of 141 trough serum samples from patients treated with voriconazole. All validation parameters met the criteria set out in FDA guidelines for bioanalytical methods. A high interpatient and intrapatient variability was observed in clinical samples. This method is accurate enough to perform therapeutic drug monitoring in patients receiving voriconazole treatment. PMID- 22776377 TI - Type I interferon and pattern recognition receptor signaling following particulate matter inhalation. AB - BACKGROUND: Welding, a process that generates an aerosol containing gases and metal-rich particulates, induces adverse physiological effects including inflammation, immunosuppression and cardiovascular dysfunction. This study utilized microarray technology and subsequent pathway analysis as an exploratory search for markers/mechanisms of in vivo systemic effects following inhalation. Mice were exposed by inhalation to gas metal arc - stainless steel (GMA-SS) welding fume at 40 mg/m3 for 3 hr/d for 10 d and sacrificed 4 hr, 14 d and 28 d post-exposure. Whole blood cells, aorta and lung were harvested for global gene expression analysis with subsequent Ingenuity Pathway Analysis and confirmatory qRT-PCR. Serum was collected for protein profiling. RESULTS: The novel finding was a dominant type I interferon signaling network with the transcription factor Irf7 as a central component maintained through 28 d. Remarkably, these effects showed consistency across all tissues indicating a systemic type I interferon response that was complemented by changes in serum proteins (decreased MMP-9, CRP and increased VCAM1, oncostatin M, IP-10). In addition, pulmonary expression of interferon alpha and beta and Irf7 specific pattern recognition receptors (PRR) and signaling molecules (Ddx58, Ifih1, Dhx58, ISGF3) were induced, an effect that showed specificity when compared to other inflammatory exposures. Also, a canonical pathway indicated a coordinated response of multiple PRR and associated signaling molecules (Tlr7, Tlr2, Clec7a, Nlrp3, Myd88) to inhalation of GMA-SS. CONCLUSION: This methodological approach has the potential to identify consistent, prominent and/or novel pathways and provides insight into mechanisms that contribute to pulmonary and systemic effects following toxicant exposure. PMID- 22776379 TI - Are expedition medical kits too dangerous to carry? PMID- 22776378 TI - Discontinuities in Rap1 activity determine epithelial cell morphology within the developing wing of Drosophila. AB - Mechanisms that govern cell-fate specification within developing epithelia have been intensely investigated, with many of the critical intercellular signaling pathways identified, and well characterized. Much less is known, however, about downstream events that drive the morphological differentiation of these cells, once their fate has been determined. In the Drosophila wing-blade epithelium, two cell types predominate: vein and intervein. After cell proliferation is complete and adhesive cell-cell contacts have been refined, the vast majority of intervein cells adopt a hexagonal morphology. Within vein territories, however, cell-shape refinement results in trapezoids. Signaling events that differentiate between vein and intervein cell fates are well understood, but the genetic pathways underlying vein/intervein cyto-architectural differences remain largely undescribed. We show here that the Rap1 GTPase plays a critical role in determining cell-type-specific morphologies within the developing wing epithelium. Rap1, together with its effector Canoe, promotes symmetric distribution of the adhesion molecule DE-cadherin about the apicolateral circumference of epithelial cells. We provide evidence that in presumptive vein tissue Rap1/Canoe activity is down-regulated, resulting in adhesive asymmetries and non-hexagonal cell morphologies. In particular Canoe levels are reduced in vein cells as they morphologically differentiate. We also demonstrate that over expression of Rap1 disrupts vein formation both in the developing epithelium and the adult wing blade. Therefore, vein/intervein morphological differences result, at least in part, from the patterned regulation of Rap1 activity. PMID- 22776380 TI - Targeting public health events on ships. PMID- 22776381 TI - Physiological and psychological illness symptoms at high altitude and their relationship with acute mountain sickness: a prospective cohort study. AB - BACKGROUND: The aim of this prospective observational cohort study was to investigate relationships between acute mountain sickness (AMS) and physical and mental health during a high altitude expedition. METHODS: Forty-four participants (mean age, 34 +/- 13 y; body mass index, 23.6 +/- 3.5 kg.m(2) ; 57% male) completed the Dhaulagiri base camp trek in Nepal, a 19-day expedition attaining 5,372 m. Participants self-reported the following daily physical and mental health: AMS (defined by Lake Louise diagnosis and individual and total symptom scores), upper respiratory symptoms, diarrhea, and anxiety, plus physiological and behavioral factors. RESULTS: The rate of Lake Louise-defined AMS per 100 person days was 9.2 (95% CI: 7.2-11.7). All investigated illnesses except diarrhea increased with altitude (all p < 0.001 by analysis of variance). Total AMS symptom score was associated with a lower arterial oxygen saturation, higher resting heart rate, more upper respiratory and diarrhea symptoms, greater anxiety, and lower fluid intake (all p < 0.02 by longitudinal multiple regression analyses). However, only upper respiratory symptoms, heart rate, arterial oxygen saturation, and fluid intake predicted future AMS symptoms [eg, an increase in upper respiratory symptoms by 5 units predicted an increase in the following day's AMS total symptom score by 0.72 units (0.54-0.89)]. CONCLUSIONS: Upper respiratory symptoms and anxiety increasingly contributed to symptom burden as altitude was gained. Data were consistent with increased heart rate, decreased arterial oxygen saturation, reduced fluid intake, and upper respiratory symptoms being causally associated with AMS. Upper respiratory symptoms and fluid intake are the simplest targets for intervention to reduce AMS during high altitude exposure. PMID- 22776382 TI - Acute mountain sickness impact among travelers to Cusco, Peru. AB - BACKGROUND: Increasing numbers of travelers are visiting high altitude locations in the Andes. The epidemiology of acute mountain sickness (AMS) among tourists to high altitude in South America is not well understood. METHODS: A cross-sectional study to evaluate the epidemiology, pre-travel preparation, and impact of AMS among travelers to Cusco, Peru (3,400 m) was performed at Cusco's International Airport during June 2010. Foreign travelers, 18 years or older, staying 15 days or less, departing Cusco were invited to participate. Demographic, itinerary, and behavioral data were collected. The Lake Louise Clinical score (LLCS) was used to assess AMS symptoms. RESULTS: In total, 991 travelers participated, median age 32 years (interquartile range 25-49), 55.5% female, 86.7% tourists, mostly from the United States (48.2%) and England (8.1%). Most (76.7%) flew from sea level to Cusco and 30.5% visited high altitude in the previous 2 months. Only 29.1% received AMS advice from a physician, 19% recalled advice on acetazolamide. Coca leaf products (62.8%) were used more often than acetazolamide (16.6%) for prevention. AMS was reported by 48.5% and 17.1% had severe AMS. One in five travelers with AMS altered their travel plans. Travelers older than 60 years, with recent high altitude exposure, who visited lower cities in their itinerary, or used acetazolamide were less likely to have AMS. Using coca leaf products was associated with increased AMS frequency. CONCLUSIONS: AMS was common and adversely impacted plans of one in five travelers. Acetazolamide was associated with decreased AMS but was prescribed infrequently. Other preventive measures were not associated with a decrease in AMS in this population. Pre-travel preparation was suboptimal. PMID- 22776384 TI - Measles, rubella, and varicella among the crew of a cruise ship sailing from Florida, United States, 2006. AB - BACKGROUND: Cruise ship outbreaks of vaccine-preventable diseases (VPD) such as rubella and varicella have been previously associated with introduction and spread among susceptible crew members originating from countries with endemic transmission of these diseases. METHODS: During February to April 2006, we investigated a cluster of rash illnesses due to measles, rubella, or varicella on a cruise ship sailing from Florida to the Caribbean. Case-finding measures included review of medical logs, active surveillance for rash illness among crew members, and passive surveillance for rash illness in the ship's infirmary lasting two incubation periods from the last case of measles. Passengers with potential exposure to these VPD were notified by letters. All susceptible crew members with potential exposure were administered the measles, mumps, and rubella vaccine after informed consent. RESULTS: A total of 16 cases were identified only among crew members: 1 rubella, 3 measles (two-generation spread), 11 varicella (three-generation spread), and 1 unknown diagnosis. Of 1,197 crew members evaluated, 4 had proof of immunity to measles and rubella. Based on passive surveillance, no cases were identified among passengers, the majority of whom resided in the United States. CONCLUSION: The international makeup of the population aboard cruise ships combined with their semi-enclosed environment has the potential to facilitate introduction and spread of VPD such as measles, rubella, and varicella onboard and into communities. Cruise lines should ensure crew members have evidence of immunity to these diseases. Passengers should be up to date with all vaccinations, including those that are travel-specific, prior to embarking on cruise travel. PMID- 22776383 TI - Management and control of varicella on cruise ships: a collaborative approach to promoting public health. AB - BACKGROUND: In most years varicella is the vaccine-preventable disease most frequently reported to Centers for Disease Control and Prevention (CDC) by cruise ships. Since 2005, CDC has received numerous isolated case reports of varicella among crew members and has investigated varicella outbreaks aboard vessels sailing into and from US seaports. METHODS: CDC investigators reviewed electronic varicella case reports from 2005 to 2009 and outbreak reports from 2009 to characterize the response and control efforts implemented by cruise ships in accordance with CDC protocols. Outbreak reports from 2009 were manually reviewed for details of case identification, contact investigations, isolation and restriction of cases and contacts, respectively, and number of contacts administered varicella vaccine post-exposure by cruise lines. RESULTS: During 2005 to 2009, cruise ships reported 278 cases of varicella to CDC among predominantly male (80%) crew members, three-quarters of whom were residents of Caribbean countries, Indonesia, the Philippines, or India, and whose median age was 29 years. Cases were more commonly reported during spring and winter months. During 2009, cruise ships reported 94 varicella cases among crew members of which 66 (70%) were associated with 18 reported varicella outbreaks. Outbreak response included isolation of 66 (100%) of 66 cases, restriction of 66 (26%) of 255 crew contacts, and administration of post-exposure vaccine to 522 close contacts and other susceptible crew members per standard CDC recommendations. DISCUSSION: Most cases reported to CDC during 2005 to 2009 were among non-US resident crew members. Overall, cruise lines sailing into North America have the onboard capability to manage varicella cases and outbreaks and appear responsive to CDC recommendations. Cruise lines should continue to implement CDC-recommended response protocols to curtail outbreaks rapidly and should consider whether pre placement varicella immunity screening and vaccination of crew members is a cost effective option for their respective fleet operations. PMID- 22776385 TI - Outbreak of ciguatera fish poisoning on a cargo ship in the port of hamburg. AB - BACKGROUND: Ciguatera fish poisoning is a travel-related illness characterized by a combination of gastrointestinal and neurological symptoms in persons who eat ciguatoxic seafood in endemic areas. METHODS: In 2009, an outbreak of the disease on a refrigerator vessel in the port of Hamburg was investigated. The ship's crew fell ill after they ate fish from a catch in the Caribbean 2 weeks earlier. All 15 sailors on board were examined by port medical officers. Samples of blood and stool specimens were taken from symptomatic sailors. The frozen fish was secured for the prevention of further disease spreading and additional diagnostic tests. RESULTS: All but one sailor ate the fish. The intoxication resulted in gastrointestinal or neurological symptoms in all 14 sailors who consumed the fish and persisted in varying degrees in 93% of sailors over at least 14 days. No fatality occurred, but two seamen were "unfit for duty" on the ship due to severity of symptoms. The diagnosis was supported by the fact that all seafarers who consumed the same reef fish, experienced typical signs, symptoms, and time course consistent with ciguatera fish poisoning. The fish from the catch in the Caribbean was identified as Caranx sexfasciatus (Bigeye Trevally) and Cephalopholis miniata (Red Grouper). An experimental assay later confirmed presence of the ciguatoxin in the fish. CONCLUSIONS: Sailors are an occupational group at risk for ciguatera fish poisoning due to potentially unsafe food sources during international travel. Even if no fatality occurred, the disease affected marine operations due to high attack rates and chronicity of symptoms. Medical doctors must be aware that ciguatera fish poisoning is a risk for seafarers traveling in tropical and subtropical areas. Stocking of food in affected ports from safe sources, adequate training of ship cooks, and informing sailors about the risk of fishing are needed to prevent disease occurrence in seafarers in international trade and traffic. PMID- 22776386 TI - Travel-related change of residence leads to a transitory stress reaction in humans. AB - OBJECTIVE: It is well known that animals show a stress response when confronted with a novel environment. The aim of the this study was to investigate whether humans show a similar response by studying the reaction to a travel-related transitory change of residence. METHOD: Forty-eight individuals (32 women, 16 men, age 40-83 years) traveling to a health resort approximately 120 km from their home town participated in the study. Individuals monitored their blood pressure (BP) twice a day 3 weeks before (baseline) and during the stay and filled out a diary stating their mood and sleep. The change of the variables relative to baseline on the day before departure, the travel day, and the day after arrival as well as 5 days after arrival were determined. RESULTS: Systolic and diastolic BPs were increased on the day before travel and diastolic BP remained increased on the travel day and the day after arrival. Sleep was poorer during the first night at the new residence. All three variables had returned to baseline level 5 days into the stay. Mood was not affected by the change of residence. CONCLUSION: The results indicate that not only the change of residence but also its anticipation affects individuals in a transient way. The findings are relevant not only for the basic understanding of the reaction to novel environments but also to travel, tourism as well as rehabilitation, and spa research. PMID- 22776387 TI - Do British commercial mountaineering expeditions carry drugs to treat high altitude illnesses? AB - High altitude commercial expeditions are increasingly popular. As high altitude illnesses are common on ascent to altitude, this study aimed to ascertain whether medications for these conditions were carried by commercial operators who run high altitude expeditions. Despite recommendations, it appears that drugs to treat high altitude illnesses are not routinely carried by commercial operators. PMID- 22776388 TI - Ascent to altitude: a benign cause of splinter hemorrhages. AB - Splinter hemorrhages appear in a variety of conditions. One identified cause is ascent to altitude, but trauma and extreme conditions have been thought to be responsible. We document the appearance of splinter hemorrhages in a group of adults during several days of easy touring at an altitude of 11,000 feet (3,350 m). PMID- 22776389 TI - Dengue virus type-3 infection in a traveler returning from Benin to Japan. AB - Dengue virus (DENV) infection is a major health threat for travelers. We describe here a case of dengue virus serotype-3 (DENV-3) infection in a traveler returning to Japan from the Republic of Benin. The isolated DENV-3 genotype 3 strain exhibited high sequence similarity to those from neighboring regions. PMID- 22776390 TI - Shigella flexneri bacteremia in two immune-competent adult travelers. AB - Shigella bacteremias are uncommon in immune-competent adults. We report two cases of Shigella flexneri bacteremia that occurred in healthy young travelers, who recovered. Self-medication with loperamide and ibuprofen without antibiotics (case 1) and concomitant falciparum malaria (case 2) were the only co-morbidities found in our two patients. PMID- 22776391 TI - Tick-borne relapsing fever with cutaneous eschar and radiculopathy, Ethiopia. AB - We report the first confirmed case of tick-borne borreliosis by molecular tools in a French traveler returning from Ethiopia with unusual presentation: the presence of cutaneous eschar after a hard tick-bite suggesting firstly to clinicians a diagnosis of tick-borne rickettsiosis. PMID- 22776392 TI - Acute febrile respiratory reaction after praziquantel treatment during asymptomatic late form of acute schistosomiasis. AB - Paradoxical reactions (Jarish Herxheimer-like reactions) have been described in patients treated with praziquantel (PZQ) during acute schistosomiasis (infected<= 3 mo), while PZQ treatment of chronic schistosomiasis is generally considered to be safe. We report an acute febrile reaction with respiratory decompensation following PZQ treatment in a 17-year-old male patient who had no potential (re)exposure to infection for at least 5 months and was therefore considered to have reached the chronic stage of disease. We speculate that the clinical manifestations in our patient constitute a very late paradoxical reaction in an unusually long acute phase of infection. PMID- 22776393 TI - Differential diagnosis of dengue fever: beware of measles! AB - Febrile exanthema is a common symptom in returning travelers. In addition to cosmopolitan diseases, etiologies specific to the visited country must be considered. As an accurate diagnosis is important, clinical suspicion should be confirmed by laboratory tests. The case reports of three brothers returning from Indonesia highlight the possibility of misdiagnosis due to the clinical similarity and serological cross reactivity of dengue fever and measles. PMID- 22776395 TI - Pre-exposure rabies vaccination in travelers: flexibility not rigidity. PMID- 22776397 TI - Neurocysticercosis and international traveling. PMID- 22776398 TI - Source of clinical malaria in mixed-species infections. PMID- 22776400 TI - Response to artificial drying until drought-induced death in different elevation populations of a high-mountain plant. AB - Climate change is imposing warmer and more arid conditions on high-mountain Mediterranean pastures. The severity of these conditions is more intense in lower elevation populations and may be critical for their survival. In this context, we asked whether local adaptation plays an important role in the response of these populations to climate change, and if so, what mechanisms are involved. Previous works, involving reciprocal sowings suggested the existence of local adaptation in lower elevation populations of Silene ciliata, a perennial representative of high-mountain Mediterranean pastures. To determine if this local advantage is due to better adaptation to more intense water stress conditions, an experiment was conducted in which S. ciliata plants from three populations located at different elevations (Low, Intermediate and High) were subjected to severe artificial water stress. Results showed that plants from the Low population had greater tolerance to water stress than plants from the High population in the earliest stages of water shortage. Furthermore, responses of proteins to specific antibodies related to drought were evaluated. Two representative late-embryogenesis abundant (LEA) proteins known to play a role in water stress tolerance were expressed throughout the drought treatment in plants from the three populations, with some pattern differences among individuals within populations. This study detected slight evidence of local adaptation to water stress in populations from different elevations. PMID- 22776401 TI - Differential expression of PDZ domain-containing proteins in human diseases - challenging topics and novel issues. AB - The general features of the PDZ domain structure and functions have been extensively studied during the last decade. PDZ domains are generally present in proteins that are involved in multiple interactions to assemble functional protein complexes that control key cellular processes. One of the best characterized functions of PDZ domain-containing proteins is control of epithelial cell polarity and cell-cell contacts. In the present review, we summarize the current knowledge on regulation of expression of certain PDZ polarity proteins localized at the intercellular junctions. In addition, we provide a critical overview of recent findings regarding the role of these proteins during development of human diseases. Complete understanding of these issues is valuable for the design of novel therapeutic intervention for common pathologies, such as cancer. PMID- 22776402 TI - Features of cancer management in obese patients. AB - There is worldwide increased in obesity prevalence and statistical almost half of United-States, including children, could be obese by 2050. Obesity in cancer patients is a major issue in oncology because weight gain and obesity account for approximately 20% of all cancer cases. Indeed, increased obesity is linked with higher risk of various types of cancer and a poorer survival. Although biological mechanisms underlying how obesity causes an increased risk of cancer are suggested, overweight as a putative direct cause of death is still debated. Numerous confounding factors may impact on survival, including comorbidities and imaging limitations. Moreover, difficulties to achieve the standard oncologic care with surgery, chemotherapy and/or radiation may also be concerned. Herein, we examined the specific features and potential adaptation of the cancer management in overweighed patients. Then, we reviewed how implicated molecular pathways may provide new strategies to decrease cancer risk and predict toxicities in an increasingly obese population. PMID- 22776399 TI - Validity of activity monitors in health and chronic disease: a systematic review. AB - The assessment of physical activity in healthy populations and in those with chronic diseases is challenging. The aim of this systematic review was to identify whether available activity monitors (AM) have been appropriately validated for use in assessing physical activity in these groups. Following a systematic literature search we found 134 papers meeting the inclusion criteria; 40 conducted in a field setting (validation against doubly labelled water), 86 in a laboratory setting (validation against a metabolic cart, metabolic chamber) and 8 in a field and laboratory setting. Correlation coefficients between AM outcomes and energy expenditure (EE) by the criterion method (doubly labelled water and metabolic cart/chamber) and percentage mean differences between EE estimation from the monitor and EE measurement by the criterion method were extracted. Random-effects meta-analyses were performed to pool the results across studies where possible. Types of devices were compared using meta-regression analyses. Most validation studies had been performed in healthy adults (n=118), with few carried out in patients with chronic diseases (n=16). For total EE, correlation coefficients were statistically significantly lower in uniaxial compared to multisensor devices. For active EE, correlations were slightly but not significantly lower in uniaxial compared to triaxial and multisensor devices. Uniaxial devices tended to underestimate TEE (-12.07 (95%CI; -18.28 to -5.85) %) compared to triaxial (-6.85 (95%CI; -18.20 to 4.49) %, p=0.37) and were statistically significantly less accurate than multisensor devices (-3.64 (95%CI; -8.97 to 1.70) %, p<0.001). TEE was underestimated during slow walking speeds in 69% of the lab validation studies compared to 37%, 30% and 37% of the studies during intermediate, fast walking speed and running, respectively. The high level of heterogeneity in the validation studies is only partly explained by the type of activity monitor and the activity monitor outcome. Triaxial and multisensor devices tend to be more valid monitors. Since activity monitors are less accurate at slow walking speeds and information about validated activity monitors in chronic disease populations is lacking, proper validation studies in these populations are needed prior to their inclusion in clinical trials. PMID- 22776403 TI - Relations between professional medical associations and healthcare industry, concerning scientific communication and continuing medical education: a policy statement from the European Society of Cardiology. AB - Physicians have an ethical duty to keep up-to-date with current knowledge. Professional medical associations such as the European Society of Cardiology (ESC) support these obligations. In Europe, the costs of continuing medical education (CME) are insufficiently supported from governments and employers; however, medical associations have been criticized for accepting alternative financial support from industry. Medical education and training in research include learning how to assess the quality and reliability of any information. There is some risk of bias in any form of scientific communication including intellectual, professional, and financial and it is essential that in particular, the latter must be acknowledged by full disclosure. It is essential that there is strong collaboration between basic and clinical researchers from academic institutions on the one hand, with engineers and scientists from the research divisions of device and pharmaceutical companies on the other. This is vital so that new diagnostic methods and treatments are developed. Promotion of advances by industry may accelerate their implementation into clinical practice. Universities now frequently exhort their academic staff to protect their intellectual property or commercialize their research. Thus, it is not commercial activity or links per se that have become the target for criticism but the perceived influence of commercial enterprises on clinical decision-making or on messages conveyed by professional medical organizations. This document offers the perspective of the ESC on the current debate, and it recommends how to minimize bias in scientific communications and CME and how to ensure proper ethical standards and transparency in relations between the medical profession and industry. PMID- 22776404 TI - Role of oxidative stress and apoptosis in the cellular response of murine macrophages upon Leishmania infection. AB - Leishmania parasites are able to survive in the macrophage, one of the most hostile environments of the vertebrate host. The present study investigated how Leishmania infection influences these host cell defence mechanisms. Macrophages were infected with antimony-susceptible and -resistant Leishmania strains. Free radical production in Leishmania-infected macrophages was measured by electron paramagnetic resonance. Apoptosis was detected with fluorescence microscopy using Annexin-V FITC labelling and with Western blotting to detect caspase-3 cleavage. Independent of their drug susceptibility profile or species background, all studied Leishmania strains induced a similar increase in free radical production in macrophages. O2 ?- production was significantly elevated during phagocytosis of the stationary phase promastigotes. Conversely, NO levels increased later in the infection and none of the strains induced capsase-3 cleavage. Leishmania donovani infection led to phosphatidylserine externalization only in RAW 264.7 cells. After an initial burst of O2 ?- during phagocytosis of promastigotes, amastigotes protect themselves by decreasing the O2 ?- production to the basal level. An increased NO production was observed 6 h after infection. Finally, induction of cell death is probably not essential in the survival of the parasite within the macrophage. PMID- 22776405 TI - A genetic bistable switch utilizing nonlinear protein degradation. AB - BACKGROUND: Bistability is a fundamental property in engineered and natural systems, conferring the ability to switch and retain states. Synthetic bistable switches in prokaryotes have mainly utilized transcriptional components in their construction. Using both transcriptional and enzymatic components, creating a hybrid system, allows for wider bistable parameter ranges in a circuit. RESULTS: In this paper, we demonstrate a tunable family of hybrid bistable switches in E. coli using both transcriptional components and an enzymatic component. The design contains two linked positive feedback loops. The first loop utilizes the lambda repressor, CI, and the second positive feedback loop incorporates the Lon protease found in Mesoplasma florum (mf-Lon). We experimentally tested for bistable behavior in exponential growth phase, and found that our hybrid bistable switch was able to retain its state in the absence of an input signal throughout 40 cycles of cell division. We also tested the transient behavior of our switch and found that switching speeds can be tuned by changing the expression rate of mf-Lon. CONCLUSIONS: To our knowledge, this work demonstrates the first use of dynamic expression of an orthogonal and heterologous protease to tune a nonlinear protein degradation circuit. The hybrid switch is potentially a more robust and tunable topology for use in prokaryotic systems. PMID- 22776407 TI - Comparison of single-incision laparoscopic high anterior resection with standard laparoscopic high anterior resection. AB - AIM: Single-incision laparoscopic surgery (SILS) is gaining momentum. The aim of the present study was to compare the outcome of SILS for high anterior resection with that of standard laparoscopic resection (StdLS). METHOD: Patients undergoing laparoscopic high anterior resection were prospectively entered into an institutional approved database. Patients treated with SILS were compared with those undergoing StdLS. RESULTS: Between April 2000 and April 2009, 327 (143 cancer) consecutive unselected patients underwent StdLS; there were three (1%) conversions and 12 (3.6%) covering ileostomies. After April 2009, 55 (29 cancer) consecutive, unselected patients underwent SILS; there were two conversions to a three-port technique (3.6%), no conversions to open resection and two (3.6%) covering ileostomies. There were no significant differences in age, sex, body mass index, hospital of operation or American Society of Anesthesiology (ASA) grade between the two groups. The operating time for SILS was significantly shorter (113 +/- 44 min for StdLS vs 79 +/- 37 min for SILS; P < 0.0001). SILS patients tolerated a normal diet earlier [10 (2-24) h for SILS vs 18 (2-96) h for StdLS] and were discharged faster [1 (1-8) days for SILS vs 3 (1-24) days for StdLS]. There were no significant differences in return to theatre, readmissions or 30-day mortality. CONCLUSION: SILS for high anterior resection is feasible, safe and quicker to perform than standard three-port laparoscopic colectomy. It seems to be associated with a faster recovery and earlier discharge. PMID- 22776406 TI - Characterization of a set of novel meiotically-active promoters in Arabidopsis. AB - BACKGROUND: Homologous recombination, together with selection, laid the foundation for traditional plant breeding. The recombination process that takes place during meiotic cell division is crucial for the creation of novel variations of highly desired traits by breeders. Gaining control over this process is important for molecular breeding to achieve more precise, large-scale and quicker plant improvement. As conventional ubiquitous promoters are neither tissue-specific nor efficient in driving gene expression in meiocytes, promoters with high meiotic activities are potential candidates for manipulating the recombination process. So far, only a few meiotically-active promoters have been reported. Recently developed techniques to profile the transcriptome landscape of isolated meiocytes provided the means to discover promoters from genes that are actively expressed in meiosis. RESULTS: In a screen for meiotically-active promoters, we examined ten promoter sequences that are associated with novel meiotic candidate genes. Each promoter was tested by expressing a GFP reporter gene in Arabidopsis. Characterization of regulatory regions revealed that these meiotically-active promoters possessed conserved motifs and motif arrangement. Some of the promoters unite optimal properties which are invaluable for meiosis directed studies such as delivering specific gene expression in early meiosis I and/or meiosis II. Furthermore, the examination of homologs of the corresponding genes within green plants points to a great potential of applying the information from Arabidopsis to other species, especially crop plants. CONCLUSIONS: We identified ten novel meiotically-active promoters; which, along with their homologs, are prime candidates to specifically drive gene expression during meiosis in plants and can thus provide important tools for meiosis study and crop breeding. PMID- 22776408 TI - Enhanced de novo alloantibody and antibody-mediated injury in rhesus macaques. AB - Chronic allograft rejection is a major impediment to long-term transplant success. Humoral immune responses to alloantigens are a growing clinical problem in transplantation, with mounting evidence associating alloantibodies with the development of chronic rejection. Nearly a third of transplant recipients develop de novo antibodies, for which no established therapies are effective at preventing or eliminating, highlighting the need for a nonhuman primate model of antibody-mediated rejection. In this report, we demonstrate that depletion using anti-CD3 immunotoxin (IT) combined with maintenance immunosuppression that included tacrolimus with or without alefacept reliably prolonged renal allograft survival in rhesus monkeys. In these animals, a preferential skewing toward CD4 repopulation and proliferation was observed, particularly with the addition of alefacept. Furthermore, alefacept-treated animals demonstrated increased alloantibody production (100%) and morphologic features of antibody-mediated injury. In vitro, alefacept was found to enhance CD4 effector memory T cell proliferation. In conclusion, alefacept administration after depletion and with tacrolimus promotes a CD4+memory T cell and alloantibody response, with morphologic changes reflecting antibody-mediated allograft injury. Early and consistent de novo alloantibody production with associated histological changes makes this nonhuman primate model an attractive candidate for evaluating targeted therapeutics. PMID- 22776409 TI - Associations between vitamin D, disease activity, and clinical response to therapy in rheumatoid arthritis. AB - OBJECTIVES: Vitamin D deficiency is a potential risk factor for autoimmunity. Prior studies of the association between vitamin D levels and rheumatoid arthritis (RA) disease activity have yielded conflicting results. METHODS: Serum 25(OH)vitamin D levels were measured at baseline in 499 participants with active RA, ages 18-85 years, enrolled in a randomised clinical trial of golimumab (Go Before Trial). Subjects were methotrexate and biologic therapy naive. Multivariable linear regression was used to assess associations between vitamin D levels and disease activity scores (DAS28), van der Heijde-Sharp (vdHS) erosion scores, and serum inflammatory markers. Generalised estimating equations were used to evaluate the associations between vitamin D status and the response to therapy over 52 weeks, using the DAS28 and ACR response. RESULTS: Forty-eight percent of participants were vitamin D deficient, defined as serum 25(OH)vitamin D <20 ng/mL. Deficiency was not associated with greater DAS28 (beta-0.021 [95% CI -0.22, 0.18]), adjusted for age, race, sex, BMI, disease duration and glomerular filtration rate. Vitamin D deficiency was not associated with baseline vdHS scores or inflammatory markers in adjusted or unadjusted models. There was no association between baseline vitamin D deficiency and change in DAS28 (beta = 0.024 [-0.30, 0.25]), proportion meeting ACR response (OR 0.82 [0.56, 1.20]), or radiographic progression at 52 weeks (OR 0.91 [0.59-1.40]). CONCLUSIONS: Vitamin D levels were not associated with RA disease activity, inflammatory markers, or vdHS scores at baseline. Furthermore, there was no association between baseline vitamin D level and response to therapy or radiographic progression. PMID- 22776410 TI - Early fetal anatomical sonography. AB - Over the past decade, prenatal screening and diagnosis has moved from the second into the first trimester, with aneuploidy screening becoming both feasible and effective. With vast improvements in ultrasound technology, sonologists can now image the fetus in greater detail at all gestational ages. In the hands of experienced sonographers, anatomic surveys between 11 and 14 weeks can be carried out with good visualisation rates of many structures. It is important to be familiar with the normal development of the embryo and fetus, and to be aware of the major anatomical landmarks whose absence or presence may be deemed normal or abnormal depending on the gestational age. Some structural abnormalities will nearly always be detected, some will never be and some are potentially detectable depending on a number of factors. PMID- 22776411 TI - Corticosteroid treatment inhibits airway hyperresponsiveness and lung injury in a murine model of chemical-induced airway inflammation. AB - CONTEXT: Exposure to toxic alkylating mustard agents causes both acute and long term effects to the lungs as indicated by increased number of inflammatory cells in airways, lung edema and lung tissue fibrosis. We have previously demonstrated that treatment with the corticosteroid dexamethasone 1 h after lung exposure to the nitrogen mustard analog melphalan protects mice from acute and sub-acute inflammatory responses, as well as from lung tissue fibrosis. OBJECTIVE: In order to address the importance of early anti-inflammatory treatment, we investigated the therapeutic effect of dexamethasone administered 1, 2 or 6 h following exposure to melphalan. METHODS: C57BL/6 mice were exposed to melphalan and treated with dexamethasone 1, 2 or 6 h after exposure. Twenty hours or 14 days post exposure mice were subjected to analysis of respiratory mechanics where the effects of incremental doses of methacholine on central and peripheral lung components were measured. We also determined the amount of inflammatory cells in the bronchoalveolar lavage fluid and measured the amount of collagen content in the lungs. RESULTS: Melphalan exposure increased airway hyperresponsiveness in both central and peripheral airways and induced an airway inflammation dominated by infiltration of macrophages and neutrophils. Dexamethasone given 1 h after exposure to melphalan provided better protection against airway inflammation than administration 2 or 6 h after exposure. Collagen deposition 14 days after exposure was decreased due to dexamethasone treatment. CONCLUSION: Early treatment with dexamethasone is important in order to reduce the airway hyperresponsiveness and inflammation caused by toxic alkylating mustards such as melphalan. PMID- 22776412 TI - Comparative structure and function analyses of native and his-tagged forms of dihydrodipicolinate reductase from methicillin-resistant Staphylococcus aureus. AB - Given the rise of multi drug resistant bacterial strains, such as methicillin resistant Staphylococcus aureus (MRSA), there is an urgent need to discover new antimicrobial agents. A validated but as yet unexplored target for new antibiotics is dihydrodipicolinate reductase (DHDPR), an enzyme that catalyzes the second step of the lysine biosynthesis pathway in bacteria. We report here the cloning, expression and purification of N-terminally his-tagged recombinant DHDPR from MRSA (6H-MRSA-DHDPR) and compare its secondary and quaternary structure with the wild type (MRSA-DHDPR) enzyme. Comparative analyses demonstrate that recombinant 6H-MRSA-DHDPR is folded and adopts the native tetrameric quaternary structure in solution. Furthermore, kinetic studies show 6H MRSA-DHDPR is functional, displaying parameters for K(m)(NADH) of 6.0 MUM, K(m)(DHDP) of 22 MUM, and k(cat) of 21s(-1), which are similar to those reported for the native enzyme. The solution properties and stability of the 6H-MRSA-DHDPR enzyme are also reported in varying physicochemical conditions. PMID- 22776413 TI - Stem cell therapy for craniofacial bone regeneration: a randomized, controlled feasibility trial. AB - Stem cell therapy offers potential in the regeneration of craniofacial bone defects; however, it has not been studied clinically. Tissue repair cells (TRCs) isolated from bone marrow represent a mixed stem and progenitor population enriched in CD90- and CD14-positive cells. In this phase I/II, randomized, controlled feasibility trial, we investigated TRC cell therapy to reconstruct localized craniofacial bone defects. Twenty-four patients requiring localized reconstruction of jawbone defects participated in this longitudinal trial. For regenerative therapy, patients were randomized to receive either guided bone regeneration (GBR) or TRC transplantation. At 6 or 12 weeks following treatment, clinical and radiographic assessments of bone repair were performed. Bone biopsies were harvested and underwent quantitative micro-computed tomographic (MUCT) and bone histomorphometric analyses. Oral implants were installed, subsequently restored, and functionally loaded with tooth restorations. Reconstructed sites were assessed for 1 year following therapy. No study-related, serious adverse events were reported. Following therapy, clinical, radiographic, tomographic, and histological measures demonstrated that TRC therapy accelerated alveolar bone regeneration compared to GBR therapy. Additionally, TRC treatment significantly reduced the need for secondary bone grafting at the time of oral implant placement with a five fold decrease in implant bony dehiscence exposure (residual bone defects) as compared to GBR-treated sites(p < 0.01). Transplantation of TRCs for treatment of alveolar bone defects appears safe and accelerates bone regeneration, enabling jawbone reconstruction with oral implants. The results from this trial support expanded studies of TRC therapy in the treatment of craniofacial deformities (ClinicalTrials.gov number CT00755911). PMID- 22776415 TI - Estimation of preoperative uterine weight in uterine myoma and uterine adenomyosis. AB - INTRODUCTION: Uterine myoma and uterine adenomyosis frequently occur in sexually mature women. Total hysterectomy is the treatment of choice when the symptoms are severe. To select an operative procedure from abdominal, vaginal, and laparoscopic methods, precise estimation of the preoperative uterine weight is desired. In this study, we estimated the preoperative uterine weight with preoperative images in cases of uterine myoma and uterine adenomyosis. METHODS: We evaluated 403 patients with uterine myoma or uterine adenomyosis (uterus < 1000 g) between 1996 and 2010. All patients underwent a preoperative MRI and received a hysterectomy with the uterine weight recorded. Based on MR images, we measured (in centimeters) the maximum longitudinal diameter in the sagittal section (a), the maximum lateral diameter (b) and the maximum longitudinal diameter in the transverse section (c) of each uterus. A correlation coefficient was calculated between the weight of the removed uterus and the value of a * b * c for each individual uterus. Also, a regression analysis was performed between x (the value of a * b * c) and y (weight of the removed uterus). RESULTS: A strong correlation was shown between the weight of the removed uterus and the value of a * b * c (r = 0.81, P < 0.01). As a result of the regression analysis, the regression equation y = 0.35x + 107 (R(2) = 0.66, P < 0.01) was obtained. CONCLUSION: In this study, the estimated weight of the uterus was calculated by the formula y = 0.35x + 107 (x = a * b * c), and this could be the determining factor in choosing a surgical method for hysterectomy. PMID- 22776414 TI - Sesquiterpene lactones isolated from indigenous Middle Eastern plants inhibit tumor promoter-induced transformation of JB6 cells. AB - BACKGROUND: Sesquiterpene lactones (SL) are plant secondary metabolites that are known for their anti-fungal, anti-bacterial, anti-inflammatory, and anti-tumor properties. Considering that several SL-derived drugs are currently in cancer clinical trials, we have tested two SL molecules, 3-beta-methoxy-iso-seco tanapartholide (beta-tan) isolated from Achillea falcata and salograviolide A (Sal A) isolated from Centaurea ainetensis, for their anti-tumor properties. We used the mouse epidermal JB6P + cells as a model for tumor promotion and cellular transformation. Key players that are involved in cellular transformation and tumorigenesis are the AP-1 and NF-kappaB transcription factors; therefore, we assessed how beta-tan and Sal A modulate their signaling pathways in JB6P + cells. METHODS: The effects of beta-tan and Sal A on the growth of normal and neoplastic keratinocytes and on the tumor promotion-responsive JB6P + cells were determined using the MTT assay. Anchorage-independent cell growth transformation assays were used to evaluate the anti-tumor promoting properties of these SL molecules in JB6P + cells and dual luciferase reporter assays and western blot analysis were used to investigate their effects on tumor promoter-induced AP-1 and NF-kappaB activities and protein levels of key AP-1 and NF-kB target genes. RESULTS: beta-tan and Sal A selectively inhibited tumor promoter-induced cell growth and transformation of JB6P + cells at concentrations that do not affect JB6P + and primary keratinocytes basal cell growth. In addition, both molecules reduced basal and tumor promoter-induced NF-kappaB transcriptional activities, differentially regulated basal and tumor promoter-induced AP-1 transcriptional activities, and modulated key players of the AP-1 and NF-kappaB signaling pathways. CONCLUSIONS: These results highlight the anti-tumor promoting properties of beta-tan and Sal A. These SL molecules isolated from two plant species native to the Middle East may provide opportunities for complementary medicine practices. PMID- 22776416 TI - Cocultivation of phytopathogenic Fusarium and Alternaria strains affects fungal growth and mycotoxin production. AB - AIMS: A laboratory study was conducted to evaluate the influence of cocultivation of toxigenic Fusarium (F.) and Alternaria (A.) fungi with respect to growth and mycotoxin production. METHODS AND RESULTS: Fusarium culmorum Fc13, Fusarium graminearum Fg23 and two Alternaria tenuissima isolates (At18 and At220) were simultaneously or consecutively co-incubated on wheat kernels in an in vitro test system. Fungal biomass was quantified by determining ergosterol content. Three Fusarium toxins (DON, NIV and ZON) and three Alternaria toxins (AOH, AME and ALT) were analysed by a newly developed HPLC/MS/MS method. In simultaneous cocultures, the fungal biomass was enhanced up to 460% compared with individual cultures; Alternaria toxins were considerably depressed down to <5%. Combining At18 and At220 with Fg23 inhibited the toxin production of both fungal partners. In contrast, Fc13 increased its DON and ZON production in competitive interaction with both A. strains. CONCLUSIONS: The interfungal competitive effects aid the understanding of the processes of competition of both fungi in natural environments and the involvement of mycotoxins as antifungal factors. SIGNIFICANCE AND IMPACT OF STUDY: Cocultivation significantly affects fungal growth and mycotoxin production of phytopathogenic Alternaria and Fusarium strains. The impact of mycotoxins on the interfungal competition is highlighted. PMID- 22776417 TI - Synthesis and biological evaluation of novel unsaturated carboxysteroids as human 5alpha-reductase inhibitors: a legitimate approach. AB - In the present study, novel steroidal 17a-substituted 3-cyano-17a-aza-D-homo-3,5 androstadien-17-ones (12-19) and 17a-substituted 17-oxo-17a-aza-D-homo-3,5 androstadien-3-oic acids (20-26) were synthesized from dehydroepiandrosterone acetate (6) along with 17-oxo-19-nor-3,5-androstadien-3-oic acid (30) through a multistep synthesis. Compounds were evaluated for their in vitro 5alpha-reductase inhibitory activity by measuring the conversion of [(3)H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5alpha-reductase inhibitory activity was also determined using rat prostate weighing method. Compounds 21-23 and 25 showed potent inhibition of 5alpha-reductase II enzyme with IC(50) values of 54.1 +/- 9.5, 22.1 +/- 2.4, 72.8 +/- 2.3 and 26.5 +/- 4.4 nM respectively as compared to Finasteride (30.3 nM) along with a significant (p < 0.05) reduction in rat prostate weight. PMID- 22776419 TI - Anxiety disorders and salivary cortisol levels in older adults: a population based study. AB - CONTEXT: The hypothalamic-pituitary-adrenal (HPA) axis is one of the body's main systems that controls response to stress. It acts through the hormone cortisol. While the dysregulation of cortisol has been associated with anxiety disorders, the evidence is inconsistent. Moreover, only a few small studies have assessed this relationship in older adults. OBJECTIVE: To determine whether in adults aged 65 years and over there is a difference in daily cortisol pattern between those with and without an anxiety disorder. METHODS: The study population comprised 1788 older adults from a population-based cohort. The Munich version of the Composite International Diagnostic Interview was used to diagnose anxiety disorders (generalized anxiety disorder, social phobia, specific phobia, agoraphobia and panic disorder). The cortisol awakening response and total cortisol secretion over the day were calculated from cortisol levels in four saliva samples taken over the course of one day (at awakening, 30min after awakening, at 1700h, at bedtime). RESULTS: Older adults with an anxiety disorder (n=145, median duration since first symptoms 41 years) had a lower cortisol awakening response (p=0.02) than those without such a disorder (n=1643). This association was most prominent in those with generalized anxiety disorder (p=0.008), but was not associated with the extent of chronicity of anxiety disorders. CONCLUSION: Older adults from the general population with long-lasting anxiety disorders had a lower cortisol awakening response than those without. This is consistent with the notion that chronic anxiety may result in downregulation of HPA-axis activity. Longitudinal studies are needed to confirm this mechanism. PMID- 22776418 TI - Role of capsaicin-sensitive C-fiber afferents in neuropathic pain-induced synaptic potentiation in the nociceptive amygdala. AB - BACKGROUND: Neurons in the capsular part of the central nucleus of the amygdala (CeC), a region also called "nociceptive amygdala," receive nociceptive information from the dorsal horn via afferent pathways relayed from the lateral parabrachial nucleus (LPB). As the central amygdala is known to be involved in the acquisition and expression of emotion, this pathway is thought to play central roles in the generation of affective responses to nociceptive inputs. Excitatory synaptic transmission between afferents arising from the LPB and these CeC neurons is potentiated in arthritic, visceral, neuropathic, inflammatory and muscle pain models. In neuropathic pain models following spinal nerve ligation (SNL), in which we previously showed a robust LPB-CeC potentiation, the principal behavioral symptom is tactile allodynia triggered by non-C-fiber low-threshold mechanoreceptor afferents. Conversely, recent anatomical studies have revealed that most of the spinal neurons projecting to the LPB receive C-fiber afferent inputs. Here, we examined the hypothesis that these C-fiber-mediated inputs are necessary for the full establishment of robust synaptic potentiation of LPB-CeC transmission in the rats with neuropathic pain. RESULTS: Postnatal capsaicin treatment, which has been shown to denervate the C-fibers expressing transient receptor potential vanilloid type-1 (TRPV1) channels, completely abolished eye wiping responses to capsaicin eye instillation in rats, but this treatment did not affect mechanical allodynia in the nerve-ligated animals. However, the postnatal capsaicin treatment prevented LPB-CeC synaptic potentiation after SNL, unlike in the vehicle-treated rats, primarily due to the decreased incidence of potentiated transmission by elimination of TRPV1-expressing C-fiber afferents. CONCLUSIONS: C-fiber-mediated afferents in the nerve-ligated animals may be a required facilitator of the establishment of nerve injury-evoked synaptic potentiation in the CeC. These inputs might play essential roles in the chronic pain-induced plastic changes in the central network linking nociception and negative emotion. PMID- 22776420 TI - Sympathetic activity and hypothalamo-pituitary-adrenal axis activity during sleep in post-traumatic stress disorder: a study assessing polysomnography with simultaneous blood sampling. AB - BACKGROUND: Nightmares and insomnia in PTSD are hallmark symptoms, yet poorly understood in comparison to the advances toward a biological framework for the disorder. According to polysomnography (PSG), only minor changes in sleep architecture were described. This warrants alternative methods for assessing sleep regulation in PTSD. METHODS: After screening for obstructive sleep apnea and period limb movement disorder, veterans with PTSD (n=13), trauma controls (TCs, n=17) and healthy controls (HCs, n=15) slept in our sleep laboratory on two consecutive nights with an IV catheter out of which blood was sampled every 20min from 22:00h to 08:00h. Nocturnal levels of plasma adrenocorticotropic hormone (ACTH), cortisol, melatonin were assessed in conjunction with PSG registration, as well as subjective sleep parameters. RESULTS: PTSD patients showed a significant increase in awakenings during sleep in comparison to both control groups. These awakenings were correlated with ACTH levels during the night, and with the subjective perception of sleep depth. Also, heart rate (HR) was significantly increased in PTSD patients as compared with both control groups. The diurnal regulation of ACTH, cortisol and melatonin appeared undisturbed. PTSD patients exhibited lower cortisol levels at borderline significance (p=0.056) during the first half of the night. ACTH levels and cortisol levels during the first half of the night were inversely related to slow wave sleep (SWS). CONCLUSION: This study suggests that hypothalamo-pituitary-adrenal (HPA) axis activity is related to sleep fragmentation in PTSD. Also, activity of the sympathetic nervous system (SNS) is increased during sleep in PTSD. Further research is necessary to explore the potential causal relationship between sleep problems and the activity of the HPA-axis and SNS in PTSD. PMID- 22776421 TI - Long-term stability of the cortisol awakening response over adolescence. AB - The cortisol awakening response (CAR) has been widely assessed as a measure of hypothalamic-pituitary-adrenal (HPA) axis activity. Short-term stability is high; however, little is known about the long-term stability of the CAR. Because there are indications that development in adolescence influences HPA axis activity, this study investigated the stability of the CAR over adolescence. Participants were 229 boys and 181 girls from an adolescent general population sample who were assessed in three consecutive years, at mean ages of 15.0 (SD=0.4), 16.0 (SD=0.4) and 17.0 (SD=0.4) years. Cortisol was analyzed in saliva sampled at awakening, and 30 and 60min later. Stability was investigated both as rank-order and as mean level stability. Effects of physical development during adolescence on stability were investigated as well. Rank-order stability was moderate to low, with tracking coefficients (interpretable as stability coefficients over time) of .15 (p<.001) for cortisol at awakening and .24 (p<.001) for cortisol 30 and 60min after awakening. Mean-levels of cortisol at awakening did not change, while the response to awakening increased over the years (linear slopes for cortisol 30 and 60min after awakening all p<.01). The increase may reflect the physical development of the adolescents. This is the first study, in a large population based sample, indicating that the rank-order of the CAR is stable over the course of several years. Interestingly, mean-levels of the cortisol response to awakening increased over the years, suggesting a maturation of HPA axis reactivity in relation to physical development over adolescence. Physical development should therefore be taken into account when investigating the CAR as a measure of HPA axis activity in adolescence. PMID- 22776422 TI - Stress induced hippocampal mineralocorticoid and estrogen receptor beta gene expression and long-term potentiation in male adult rats is sensitive to early life stress experience. AB - Glucocorticoid hormones and their receptors have been identified to be involved in emotional and cognitive disorders in early stressed subjects during adulthood. However, the impact of other steroid hormones and receptors has been considered less. Especially, functional roles of estrogen and estrogen receptors in male subjects are largely unknown. Therefore, we measured hippocampal concentrations of 17beta-estradiol, corticosterone and testosterone, as well as the gene expression of estrogen receptor alpha and beta (ERalpha, beta), androgen receptor (AR), glucocorticoid (GR) and mineralocorticoid (MR) receptors after stress in adulthood in maternally separated (MS+; at postnatal days 14-16 for 6h each day) and control (MS-) male rats. In vivo hippocampal long-term potentiation (LTP) serves as a cellular model of learning and memory formation. Population spike- (PSA) and the fEPSP-LTP within the dentate gyrus (DG) were reinforced by elevated platform-stress (EP-stress) in MS- but not in MS+ rats. MR- and ERbeta-mRNA were upregulated 1h after EP-stress in MS- but not in MS+ rats as compared to non stressed littermates. Infusion of an MR antagonist before LTP induction blocked early- and late-PSA- and -fEPSP-LTP, whereas blockade of ERbeta impaired only the late PSA-LTP. Application of a DNA methyltransferase (DNMT) inhibitor partly restored the LTP-reinforcement in MS+ rats, accompanied by a retrieval of ERbeta- but not MR-mRNA upregulation. Basal ERbeta gene promoter methylation was similar between groups, whereas MS+ and MS- rats showed different methylation patterns across CpG sites after EP-stress. These findings indicate a key role of ERbeta in early-stress mediated emotionality and emotion-induced late-LTP in adult male rats via DNA methylation mechanisms. PMID- 22776424 TI - Evaluation of implementation of sentinel node biopsy in Australia. AB - BACKGROUND: Sentinel node biopsy (SNB) has been a major change in surgical technique for the management of early breast cancer. In June 2008, the National Breast and Ovarian Cancer Centre (NBOCC) released evidence-based guidelines for the use of SNB in Australia. During 2010, NBOCC undertook a cohort study to identify the extent to which clinical practice in Australia reflected the recommendations for use of SNB in the 6 months after release of the guidelines. METHODS: Records obtained from four datasets, Royal Australasian College of Surgeons National Breast Cancer Audit, New South Wales Central Cancer Registry, Victorian Cancer Registry and Medicare Benefits Schedule records, were analysed to determine the extent to which the four key guideline recommendations had been implemented. This was supplemented by an audit of written SNB protocols of a sample of pathology laboratories in Australia. RESULTS: ACROSS all cohorts, between 78 and 83% of women in Australia with tumours <=3 cm had an SNB. Data were not available to indicate whether nodes were clinically negative. The likelihood of women having an SNB decreased outside the metropolitan regions, for women treated as public patients compared with private patients and as the size of the tumour increased. In 90% of procedures both preoperative lymphoscintigraphy with isotope and blue dye were used. CONCLUSION: The findings from the study confirm that best practice recommendations from the NBOCC guidelines for SNB were largely being implemented for women with early breast cancer in Australia within 6 months of their release. PMID- 22776423 TI - Regional distribution of 5alpha-reductase type 2 in the adult rat brain: an immunohistochemical analysis. AB - The enzyme 5alpha-reductase (5alphaR) catalyzes the conversion of testosterone and other Delta(4)-3-ketosteroids into their 5alpha-reduced metabolites. Of the five members of the 5alphaR family, the type 2 enzyme (5alphaR2) plays a key role in androgen metabolism, and is abundantly distributed in the urogenital system. Although 5alphaR2 has been reported to be highly expressed in the brain during early developmental stages, little is currently known on its anatomical and cellular distribution in the adult brain. Thus, the present study was designed to determine the detailed localization of 5alphaR2 in the adult rat brain, using a highly specific polyclonal antibody against this isoform. Parasagittal and coronal sections revealed 5alphaR2 immunoreactivity throughout most brain regions, with strong immunolabeling in the layers III and VI of the prefrontal and somatosensory cortex, olfactory bulb, thalamic nuclei, CA3 field of hippocampus, basolateral amygdala and Purkinje cell layer of cerebellum. Lower 5alphaR2 levels were detected in the hypothalamus and midbrain. Moreover, double labeling fluorescence with confocal laser scanning microscopy (CLSM) revealed that 5alphaR2 is localized in neurons, but not in glial cells. Specifically, the enzyme was documented in the pyramidal neurons of the cortex by CLSM analysis of simultaneous Golgi-Cox and immunofluorescent staining. Finally, low levels of 5alphaR2 expression were identified in GABAergic cells across the cortex, hippocampus and striatum. These findings show that, in the adult brain, 5alphaR2 is distributed in critical regions for behavioral regulation, suggesting that the functional role of this isoform is present throughout the entire lifespan of the individual. PMID- 22776425 TI - Age-dependent decline of motor neocortex but not hippocampal performance in heterozygous BDNF mice correlates with a decrease of cortical PSD-95 but an increase of hippocampal TrkB levels. AB - Brain-derived neurotrophic factor (BDNF) is a key player in learning and memory processes. However, little is known about brain area-specific functions of this neurotrophin. Here we investigated whether BDNF could differently affect motor neocortical and hippocampal-related cognitive and plastic morphologic changes in young (12-week-old) and middle-aged (30-week-old) BDNF heterozygous (BDNF+/-) and wild type (wt) mice. We found that at 30 weeks of age, BDNF+/- mice showed impaired performance in accelerating rotarod and grasping tests while preserved spatial learning in a T-maze and recognition memory in an object recognition task compared with wt mice suggesting a specific neocortical dysfunction. Accordingly, a significant reduction of synaptic markers (PSD-95 and GluR1) and corresponding puncta was observed in motor neocortex but not in hippocampus of BDNF+/- mice. Interestingly, 30-week-old BDNF+/- mice displayed increased TrkB levels in the hippocampus but not in the motor neocortex, which suggests specific hippocampal compensatory mechanisms as a consequence of BDNF decrease. In conclusion, our data indicates that BDNF could differentially regulate the neuronal micro structures and cognition in a region-specific and in an age-dependent manner. PMID- 22776427 TI - Toxoplasmosis in humans and animals in Brazil: high prevalence, high burden of disease, and epidemiology. AB - Infections by the protozoan parasite Toxoplasma gondii are widely prevalent in humans and animals in Brazil. The burden of clinical toxoplasmosis in humans is considered to be very high. The high prevalence and encouragement of the Brazilian Government provides a unique opportunity for international groups to study the epidemiology and control of toxoplasmosis in Brazil. Many early papers on toxoplasmosis in Brazil were published in Portuguese and often not available to scientists in English-speaking countries. In the present paper we review prevalence, clinical spectrum, molecular epidemiology, and control of T. gondii in humans and animals in Brazil. This knowledge should be useful to biologists, public health workers, veterinarians, and physicians. Brazil has a very high rate of T. gondii infection in humans. Up to 50% of elementary school children and 50 80% of women of child-bearing age have antibodies to T. gondii. The risks for uninfected women to acquire toxoplasmosis during pregnancy and fetal transmission are high because the environment is highly contaminated with oocysts. The burden of toxoplasmosis in congenitally infected children is also very high. From limited data on screening of infants for T. gondii IgM at birth, 5-23 children are born infected per 10 000 live births in Brazil. Based on an estimate of 1 infected child per 1000 births, 2649 children with congenital toxoplasmosis are likely to be born annually in Brazil. Most of these infected children are likely to develop symptoms or signs of clinical toxoplasmosis. Among the congenitally infected children whose clinical data are described in this review, several died soon after birth, 35% had neurological disease including hydrocephalus, microcephaly and mental retardation, 80% had ocular lesions, and in one report 40% of children had hearing loss. The severity of clinical toxoplasmosis in Brazilian children may be associated with the genetic characteristics of T. gondii isolates prevailing in animals and humans in Brazil. PMID- 22776428 TI - Detecting and investigating substrate cycles in a genome-scale human metabolic network. AB - Substrate cycles, also known as futile cycles, are cyclic metabolic routes that dissipate energy by hydrolysing cofactors such as ATP. They were first described to occur in the muscles of bumblebees and brown adipose tissue in the 1970s. A popular example is the conversion of fructose 6-phosphate to fructose 1,6 bisphosphate and back. In the present study, we analyze a large number of substrate cycles in human metabolism that consume ATP and discuss their statistics. For this purpose, we use two recently published methods (i.e. EFMEvolver and the K-shortest EFM method) to calculate samples of 100,000 and 15,000 substrate cycles, respectively. We find an unexpectedly high number of substrate cycles in human metabolism, with up to 100 reactions per cycle, utilizing reactions from up to six different compartments. An analysis of tissue specific models of liver and brain metabolism shows that there is selective pressure that acts against the uncontrolled dissipation of energy by avoiding the coexpression of enzymes belonging to the same substrate cycle. This selective force is particularly strong against futile cycles that have a high flux as a result of thermodynamic principles. PMID- 22776426 TI - Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens. AB - BACKGROUND: Since a phase I clinical trial using three HLA-A24-binding peptides from TTK protein kinase (TTK), lymphocyte antigen-6 complex locus K (LY6K), and insulin-like growth factor-II mRNA binding protein-3 (IMP3) had been shown to be promising for esophageal squamous cell carcinoma (ESCC), we further performed a multicenter, non-randomized phase II clinical trial. PATIENTS AND METHODS: Sixty ESCC patients were enrolled to evaluate OS, PFS, immunological response employing ELISPOT and pentamer assays. Each of the three peptides was administered with IFA weekly. All patients received the vaccination without knowing an HLA-A type, and the HLA types were key-opened at the analysis point. Hence, the endpoints were set to evaluate differences between HLA-A*2402-positive (24(+)) and -negative (24(-)) groups. RESULTS: The OS in the 24 (+) group (n = 35) tended to be better than that in the 24(-) group (n = 25) (MST 4.6 vs. 2.6 month, respectively, p = 0.121), although the difference was not statistically significant. However, the PFS in the 24(+) group was significantly better than that in the 24(-) group (p = 0.032). In the 24(+) group, ELISPOT assay indicated that the LY6K-, TTK-, and IMP3-specific CTL responses were observed after the vaccination in 63%, 45%, and 60% of the 24(+) group, respectively. The patients having LY6K-, TTK-, and IMP3 specific CTL responses revealed the better OS than those not having CTL induction, respectively. The patients showing the CTL induction for multiple peptides have better clinical responses. CONCLUSIONS: The immune response induced by the vaccination could make the prognosis better for advanced ESCC patients. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00995358. PMID- 22776430 TI - Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency. AB - This randomized, comparative, multinational phase 3b/4 study of patients 1-8 years postcardiac transplantation (mean 3.9 years) evaluated the effect of conversion from a calcineurin inhibitor (CNI) to sirolimus on renal function in patients with renal insufficiency. In total, 116 patients on CNI therapy with GFR 40-90 mL/min/1.73 m(2) were randomized (1:1) to sirolimus (n = 57) or CNI (n = 59). Intent-to-treat analysis showed the 1-year adjusted mean change from baseline in creatinine clearance (Cockcroft-Gault) was significantly higher with sirolimus versus CNI treatment (+3.0 vs. -1.4 mL/min/1.73 m(2) , respectively; p = 0.004). By on-therapy analysis, values were +4.7 and -2.1, respectively (p < 0.001). Acute rejection (AR) rates were numerically higher in the sirolimus group; 1 AR with hemodynamic compromise occurred in each group. A significantly higher treatment discontinuation rate due to adverse events (AEs; 33.3% vs. 0%; p < 0.001) occurred in the sirolimus group. Most common treatment-emergent AEs significantly higher in the sirolimus group were diarrhea (28.1%), rash (28.1%) and infection (47.4%). Conversion to sirolimus from CNI therapy improved renal function in cardiac transplant recipients with renal impairment, but was associated with an attendant AR risk and higher discontinuation rate attributable to AEs. PMID- 22776429 TI - Induction of anti-Ro60/anti-La by immunisation with spectrin and induction of anti-spectrin by immunisation with Ro60 and 4-hydroxy-2-nonenal-modified Ro60 immunisation. AB - OBJECTIVES: The Ro ribonucleoprotein particle, targeted in systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS), includes Ro60 (SSA) and La (SSA) autoantigens. Anti-Ro60 occurs in SLE and SS. The importance of alpha-fodrin and spectrin as well as anti-Ro and anti-fodrin/spectrin antibodies in SS and SLE, led us to hypothesise that rabbit immunisation with Ro60 or 4-hydroxy-2-nonenal modified Ro60 would induce anti-spectrin. In addition, we hypothesised that antibodies to Ro60 and La will develop in animals immunised with spectrin. METHODS: Two NZW rabbits each were immunised with 4-hydroxy-2-nonenal-modified Ro60 or unmodified Ro60. Methods used included ELISA, including an inside-out RBC membrane ELISA, and Crithidia lucilae assays. RESULTS: Commercial anti-spectrin sera bound significantly to Ro60 (OD 2.6 +/- 0.1), Ro60 multiple antigenic peptides (MAPs) (3 out of 21 Ro60 MAPs), La (OD 4.4+/-0.5), and La fragments as well as to double stranded DNA but not to BSA (OD 0.6+/-0.1). Anti-spectrin binding to purified spectrin could be inhibited by spectrin (>95%), and Ro60 or La (70%). When the binding of anti-spectrin was tested against a nested set of La fragments we found that a N4 fragment representing the C-terminal 250 aa (aa 159 to 408) bound the strongest (OD=4.12) followed by a N9 fragment (the C-terminal 36aa; aa373 to 408 (OD=1.36). Also, significant anti-spectrin antibody levels were induced by Ro60 and HNE-modified Ro60 immunisation. CONCLUSIONS: We found intermolecular epitope spreading from Ro60/La to spectrin and vice versa, and this may have pathological significance in these animal models of autoimmunity. PMID- 22776431 TI - Current outbreak of Staphylococcus aureus. PMID- 22776433 TI - Local and systemic changes in expression of resistance genes, NB-LRR genes and their putative microRNAs in Norway spruce after wounding and inoculation with the pathogen Ceratocystis polonica. AB - BACKGROUND: NB-LRR resistance proteins are involved in recognizing pathogens and other exogenous stressors in plants. Resistance proteins are the first step in induced defence responses and a better understanding of their regulation is important to understand the mechanisms of plant defence. Much of the post transcriptional regulation in plants is controlled by microRNAs (miRNA). We examined the expression of five Norway spruce miRNA that may regulate NB-LRR related transcripts in secondary phloem (bark) of resistant Norway spruce after wounding and inoculation with the necrotrophic blue stain fungus Ceratocystis polonica. RESULTS: The plants of this clone recovered from both the pathogen inoculations and wounding alone. We found local and systemic induction of the resistance marker genes PaChi4, PaPAL and PaPX3 indicative of an effective induced host defence response. There were minor local and systemic changes in the expression of five miRNAs and 21 NB-LRRs between healthy and treated plants. Only five putative NB-LRRs (PaLRR1, PaLRR3, PaLRR14, PaLRR15 and PaLRR16) showed significant increases greater than two-fold as a local response to C. polonica. Of all NB-LRRs only PaLRR3, the most highly differentially regulated NB-LRR, showed a significant increase also due to wounding. The five miRNAs showed indications of an initial local and systemic down-regulation at day 1, followed by a later increase up to and beyond the constitutive levels at day 6. However, the initial down-regulation was significant only for miR3693 and miR3705. CONCLUSIONS: Overall, local and systemic expression changes were evident only for the established resistance marker genes and PaLRR3. The minor expression changes observed both for the followed miRNAs and their predicted NB-LRR targets suggest that the expression of most NB-LRR genes are maintained close to their constitutive levels in stressed and healthy Norway spruce plants. PMID- 22776434 TI - Carbamoylated free amino acids in uremia: HOCl generates volatile protein modifying and cytotoxic oxidant species from N-carbamoyl-threonine but not threonine. AB - N-carbamoylation is the non-enzymatic reaction of cyanate with amino groups. Due to urea-formed cyanate in uremic patients beside carbamoylated proteins also free amino acid carbamoylation has been detected, a modification which has been linked to disturbed protein synthesis as NH(2)-derivatisation interferes with peptide bond formation. HOCl the product of the activated MPO/H(2)O(2)/Cl(-) system is known to react with the NH(2)-group of free amino acids to form chloramines which could exert some protective effect against protein modification and cytotoxicity induced by HOCl. As N-carbamoylation may inhibit formation of chloramines we have used N-carbamoyl-threonine as a model amino acid to study its ability to limit the reactivity of HOCl with proteins (LDL and human serum albumin) and cells (THP 1 monocytes and coronary artery endothelial cells). The data indicate that N carbamoylation completely abolished the protein- and cell-protective effect of threonine against HOCl attack. In contrast to threonine the reaction of HOCl with carbamoyl-threonine resulted in the formation of volatile oxidant species with protein modifying and cytotoxic potential. The volatile lipophilic inorganic monochloramine (NH(2)Cl) was identified as a breakdown product of this reaction. PMID- 22776435 TI - Factors influencing circumferential resection margin in rectal cancer. AB - AIM: Abdominoperineal excision (APR) has been associated with higher circumferential resection margin (CRM) involvement and local recurrence rates than extralevator APR for low rectal cancer. This study aimed to evaluate the CRMs in APR and low anterior resection (LAR) specimens and to identify factors influencing CRM involvement. METHOD: All pathological specimens from consecutive patients with rectal cancer who underwent curative resection at the Cleveland Clinic Florida, from January 2000 to July 2010, were reviewed by two pathologists. Demographics, tumour characteristics, operative data, postoperative pathology and Dworak's tumour regression grade were compared between specimens with positive and negative CRMs. RESULTS: One-hundred and fifty-four patients underwent curative APR (n = 65) or LAR (n = 69). Mean tumour size was 3.6 cm, and mean distance from the dentate line was 5.4 cm. Nine (6.8%) patients had a positive CRM (n = 6 APR, n = 3 LAR), which was associated with tumour size > 5.9 cm (P = 0.002), a distance of <= 2.6 cm from the dentate line (P = 0.013), microvascular invasion (P = 0.009), perineural invasion (P < 0.001), number of positive lymph nodes (P = 0.046) and incomplete total mesorectal excision (TME) (P < 0.001). APR specimens were three times more likely than LAR specimens to have an incomplete mesorectum (9.8%vs 2.9%, P = 0.322). CONCLUSIONS: Factors associated with a positive CRM were tumour size > 5.9 cm, a distance of <= 2.6 cm from the dentate line, incomplete TME, number of positive nodes and microvascular and perineural invasion. The incidence of a positive CRM was not significantly different between LAR and APR (n = 3 LAR and n = 6 APR). PMID- 22776436 TI - Hepatoprotective activity of Sonchus asper against carbon tetrachloride-induced injuries in male rats: a randomized controlled trial. AB - BACKGROUND: Sonchus asper (SAME) is used as a folk medicine in hepatic disorders. In this study, the hepatoprotective effects of the methanol extract of SAME was evaluated against carbon tetrachloride (CCl4)-induced liver injuries in rats. METHODS: To evaluate the hepatoprotective effects of SAME, 36 male Sprague-Dawley rats were equally divided into 6 groups. Rats of Group I (control) were given free access to approved feed and water. Rats of Group II were injected intraperitoneally with CCl4 (3 ml/kg) as a 30% solution in olive oil (v/v) twice a week for 4 weeks. Animals of Groups III (100 mg/kg) and IV (200 mg/kg) received SAME, whereas those of Group V were given silymarin via gavage (100 mg/kg) after 48 h of CCl4 treatment. Group VI received SAME (200 mg/kg) twice a week for 4 weeks without CCl4 treatment. Various parameters, such as the serum enzyme levels, serum biochemical marker levels, antioxidant enzyme activities, and liver histopathology were used to estimate the hepatoprotective efficacy of SAME. RESULTS: The administration of SAME and silymarin significantly lowered the CCl4 induced serum levels of hepatic marker enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), cholesterol, low-density lipoprotein, and triglycerides while elevating high-density lipoprotein levels. The hepatic contents of glutathione and activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase were reduced. The levels of thiobarbituric acid-reactive substances that were increased by CCl4 were brought back to control levels by the administration of SAME and silymarin. Liver histopathology showed that SAME reduced the incidence of hepatic lesions induced by CCl4 in rats. CONCLUSION: SAME may protect the liver against CCl4-induced oxidative damage in rats. PMID- 22776438 TI - Patients' perception of surgical training in private hospitals. AB - INTRODUCTION: Surgical training is traditionally a public hospital-based practice. At Epworth Private Hospital, Richmond, Victoria, there are three accredited surgical training positions and one fellowship position. We conducted a patient survey to review the patients' perspective of surgical trainees in private hospitals. METHODS: Over 6 weeks, 100 patients admitted under the surgical units with full-time surgical registrars were given a survey to complete in two parts on the training of surgeons in private hospitals. RESULTS: Seventy per cent of surveys were returned completed. Ninety per cent of respondents agreed that private hospitals should be involved in surgical training and 85.7% of patients were agreeable to having trainees involved in their operation. Only 1.4% of patients were not in agreement with surgical training in private and 8.6% of patients were neutral in their opinion. CONCLUSION: Our results clearly show that private hospital patients are generally favourably disposed to the presence and participation of surgical trainees in the private hospital setting. PMID- 22776437 TI - Augmenter of liver regeneration. AB - 'Augmenter of liver regeneration' (ALR) (also known as hepatic stimulatory substance or hepatopoietin) was originally found to promote growth of hepatocytes in the regenerating or injured liver. ALR is expressed ubiquitously in all organs, and exclusively in hepatocytes in the liver. ALR, a survival factor for hepatocytes, exhibits significant homology with ERV1 (essential for respiration and viability) protein that is essential for the survival of the yeast, Saccharomyces cerevisiae. ALR comprises 198 to 205 amino acids (approximately 22 kDa), but is post-translationally modified to three high molecular weight species (approximately 38 to 42 kDa) found in hepatocytes. ALR is present in mitochondria, cytosol, endoplasmic reticulum, and nucleus. Mitochondrial ALR may be involved in oxidative phosphorylation, but also functions as sulfhydryl oxidase and cytochrome c reductase, and causes Fe/S maturation of proteins. ALR, secreted by hepatocytes, stimulates synthesis of TNF-alpha, IL-6, and nitric oxide in Kupffer cells via a G-protein coupled receptor. While the 22 kDa rat recombinant ALR does not stimulate DNA synthesis in hepatocytes, the short form (15 kDa) of human recombinant ALR was reported to be equipotent as or even stronger than TGF-alpha or HGF as a mitogen for hepatocytes. Altered serum ALR levels in certain pathological conditions suggest that it may be a diagnostic marker for liver injury/disease. Although ALR appears to have multiple functions, the knowledge of its role in various organs, including the liver, is extremely inadequate, and it is not known whether different ALR species have distinct functions. Future research should provide better understanding of the expression and functions of this enigmatic molecule. PMID- 22776440 TI - On the predictive validity of automatically activated approach/avoidance tendencies in abstaining alcohol-dependent patients. AB - BACKGROUND: Prominent addiction models posit that automatically activated approach/avoidance tendencies play a critical role in addiction. Nevertheless, only a limited number of studies have actually documented the relationship between relapse and automatically activated approach/avoidance tendencies. We compared automatically activated approach/avoidance tendencies towards alcohol in 40 abstaining alcohol-dependent patients and 40 controls. We also examined whether individual differences in automatically activated approach/avoidance tendencies towards alcohol are predictive of relapse in patients. METHODS: A Relevant Stimulus Response Compatibility task was used to measure relative approach/avoidance tendencies. In one block of trials, participants were asked to approach alcohol-related pictures and to avoid alcohol-unrelated pictures (i.e., compatible block). In a second block of trials, participants were asked to approach alcohol-unrelated pictures and to move away from alcohol-related pictures (i.e., incompatible block). Patients were tested between 18 and 21 days after they quit drinking. Relapse was assessed 3 months after patients were discharged from the hospital. RESULTS: Whereas abstaining alcohol-dependent patients were faster to respond to incompatible trials as compared to compatible trials, participants in the control group showed the exact opposite pattern. Within the patient group, the likelihood of relapse increased as participants were faster to respond to incompatible trials relative to compatible trials. CONCLUSIONS: Unlike controls, abstaining alcohol-dependent patients revealed a relative avoidance bias rather than relative approach bias. Moreover, relapse rates were found to increase as the relative tendency to avoid alcohol increased. This finding suggests that an avoidance orientation towards alcohol can potentially be harmful in clinical samples. PMID- 22776439 TI - A histone-like protein of Helicobacter pylori protects DNA from stress damage and aids host colonization. AB - Genomic DNA in a bacterial cell is folded into a compact structure called a nucleoid, and nucleoid-associated proteins are responsible for proper assembly of active higher-order genome structures. The human gastric pathogen Helicobacter pylori express a nucleoid-associated protein encoded by the hup gene, which is the homolog to the Escherichia coli histone-like protein HU. An H. pylori hup mutant strain (X47 hup:cat) showed a defect in stationary phase survival. The X47 hup:cat mutant was more sensitive to the DNA damaging agent mitomycin C, and displayed a decreased frequency of DNA recombination, indicating Hup plays a significant role in facilitating DNA recombinational repair. The X47 hup:cat mutant was also sensitive to both oxidative and acid stress, conditions that H. pylori commonly encounters in the host. The hup mutant cells survived significantly (7-fold) less upon exposure to macrophages than the wild type strain. In a mouse infection model, the hup mutant strain displayed a greatly reduced ability to colonize host stomachs. The geometric means of colonization number for the wild type and hup mutant were 6*10(5) and 1.5*10(4)CFU/g stomachs, respectively. Complementation of the hup strain by chromosomal insertion of a functional hup gene restored oxidative stress resistance, DNA transformation frequency, and mouse colonization ability to the wild type level. We directly demonstrated that the purified His-tagged H. pylori Hup protein can protect (in vitro) an H. pylori-derived DNA fragment from oxidative damage. PMID- 22776441 TI - The efficacy of Familias Unidas on drug and alcohol outcomes for Hispanic delinquent youth: main effects and interaction effects by parental stress and social support. AB - INTRODUCTION: Drug and alcohol use disproportionately affect Hispanic youth. Despite these disparities, few empirically supported preventive interventions are available to ameliorate this public health concern among Hispanic youth. This study examined the effects of Familias Unidas, relative to Community Practice, in reducing past 90-day substance use, alcohol and marijuana dependence, and having sex while under the influence of alcohol or drugs. Additionally, this study explored whether Familias Unidas' effects varied by environmental context, namely parental stress and social support for parents. METHODS: A total of 242 delinquent Hispanic youth aged 12-17 years and their primary caregivers were randomized to either Familias Unidas or Community Practice and assessed at three time points. RESULTS: Familias Unidas was efficacious in reducing past 90-day substance use, illicit drug use, and in reducing the proportion of youth with an alcohol dependence diagnosis, relative to Community Practice. Results also showed a reduction in the proportion of youth who reported having sex while under the influence of alcohol or drugs. No differences between conditions were observed in past 90-day alcohol use or marijuana dependence. Intervention effects on illicit drug use and alcohol dependence varied by environmental context. For example, Familias Unidas was most efficacious for adolescents with parents exhibiting high stress and lower levels of social support. CONCLUSIONS: Familias Unidas was efficacious in reducing some drug and alcohol related outcomes. The findings also support the concept of targeting family-based interventions, such as Familias Unidas, for adolescents with parents exhibiting high stress and low levels of social support. PMID- 22776442 TI - Inhalation exposure to smoke from synthetic "marijuana" produces potent cannabimimetic effects in mice. AB - BACKGROUND: Use of synthetic "marijuana" has increased in recent years, produced adverse effects and prompted the temporary DEA ban of five specific cannabinoid analogs, including JWH-018. The objectives of the current study include determining the chemical content of the herbal product, Buzz, assessing its behavioral effects upon inhalation exposure to mice, determining whether CB(1) receptors mediate its pharmacological activity, and ascertaining its biodisposition in blood and various organs. METHODS: Using a nose-only exposure system, mice were exposed to smoke produced from combustion of an herbal incense product, Buzz, which contained 5.4% JWH-018. Cannabimimetic effects following smoke exposure were evaluated using the tetrad procedure, consisting of the following indices: hypomotility, antinociception, catalepsy, and hypothermia. Additionally, blood and tissues were collected for JWH-018 quantification. RESULTS: Inhalation exposure to Buzz produced dose-related tetrad effects similar to marijuana as well as dose-related increased levels of JWH-018 in the blood, brain, heart, kidney, liver, lung, and spleen. The behavioral effects were blocked by rimonabant, a CB(1) receptor antagonist. Effects produced by Buzz were similar in magnitude and time-course to those produced by marijuana, though equipotent doses of Buzz and marijuana yielded considerably lower brain levels of JWH-018 than THC for the respective materials. CONCLUSIONS: Inhalation exposure to a product containing JWH-018 penetrates into the brain and other organs and produces CB(1) receptor-mediated behavioral pharmacological effects in mice. The increased potency of JWH-018 compared to THC, the variable amount of drug added to various herbal products, and unknown toxicity, undoubtedly contribute to public health risks of synthetic cannabinoids. PMID- 22776443 TI - A profile on HIV prevalence and risk behaviors among injecting drug users in Nigeria: should we be alarmed? AB - OBJECTIVE: Injecting drug use is now recognized as a significant risk factor for HIV in sub-Saharan Africa. We evaluated prevalence and correlates of HIV among injecting drug users (IDUs) in Nigeria. METHODS: A cross sectional design using respondent driven sampling was conducted in six states in 2010. Weighted HIV prevalence and injecting risk behaviors calculated using RDS analytic tool. Logistic regression was used to determine correlates of HIV infection, stratified by state. RESULTS: Total numbers of IDUs ranged from 197 in Lagos to 273 in Cross River and Oyo states. HIV prevalence was highest in Federal Capital Territory (FCT) at 9.3%, Kaduna 5.8%, Oyo 5.1%, Kano 4.9%, CR 3.3% and Lagos 3.0%. Although >90% of participants were male, females had higher HIV prevalence in all states surveyed except FCT (range: 7.4% in CR to 37.7% in Kano). Logistic regression showed that females were significantly more likely to be HIV positive in Kano [OR=33.2, 95% CI: 6.8-160.4], Oyo [AOR=15.9, 95% CI: 3.69-68.51], Lagos [OR=15.5, 95% CI: 2.41-99.5] and Kaduna states [AOR=19.6, 95% CI: 4.4-87.6]. For injecting risk behavior, only receptive sharing was associated with HIV [AOR=7.6, 95% CI: 1.2-48.7] and [AOR=0.2, 95% CI: 0.04-0.92] in Oyo and Kaduna states respectively. CONCLUSIONS: Considerable heterogeneity in the prevalence of HIV and associated risk behaviors exist among IDUs across Nigeria. Females had higher HIV prevalence among IDUs in five of six states, suggesting a need for targeted interventions for this hidden subgroup. Further research is needed to understand HIV transmission dynamics of IDUs in Nigeria. Community-based opioid substitution therapy and needle exchange programs should be implemented without delay. PMID- 22776444 TI - Metabolomic profiling in blood from umbilical cords of low birth weight newborns. AB - BACKGROUND: Low birth weight has been linked to an increased risk to develop obesity, type 2 diabetes, and hypertension in adult life, although the mechanisms underlying the association are not well understood. The objective was to determine whether the metabolomic profile of plasma from umbilical cord differs between low and normal birth weight newborns. METHODS: Fifty healthy pregnant women and their infants were selected. The eligibility criteria were being born at term and having a normal pregnancy. Pairs were grouped according to their birth weight: low birth weight (LBW, birth weight < 10th percentile, n = 20) and control (control, birth weight between the 75th-90th percentiles, n = 30). Nuclear Magnetic Resonance (NMR) was used to generate metabolic fingerprints of umbilical cord plasma samples. Simultaneously, the metabolomic profiles of the mothers were analysed. The resulting data were subjected to chemometric, principal component and partial least squares discriminant analyses. RESULTS: Umbilical cord plasma from LBW and control newborns displayed a clearly differentiated metabolic profile. Seven metabolites were identified that discriminate the LBW from the control group. LBW newborns had lower levels of choline, proline, glutamine, alanine and glucose than did the control newborns, while plasma levels of phenylalanine and citrulline were higher in LBW newborns (p < 0.05). No significant differences were found between the two groups of mothers. CONCLUSIONS: Low birth weight newborns display a differential metabolomic profile than those of normal birth weight, a finding not present in the mothers. The meaning and the potential utility of the findings as biomarkers of risk need to be addressed in future studies. PMID- 22776445 TI - Ghrelin does not affect gastrointestinal contractility in rainbow trout and goldfish in vitro. AB - Ghrelin has been identified in rainbow trout and goldfish, and it has been shown to regulate growth hormone release and food intake in these species as seen in mammals. The aim of this study was to investigate the functional role of ghrelin in regulation of gastrointestinal contractility in both fishes. Neither rainbow trout ghrelin nor rat ghrelin affected the contractility of gastrointestinal strips of rainbow trout. Similarly, goldfish ghrelin-17 and rat ghrelin did not cause marked contraction in the goldfish intestinal bulb. Detail examinations using the goldfish intestine revealed that human neurotensin, substance-P, goldfish neuromedine-U and carbachol showed apparent contractile activities in the intestinal strips. Electrical field stimulation (EFS, 1-20 Hz) caused a frequency-dependent contraction of the intestinal bulb. Atropine partially inhibited and tetrodotoxin abolished the EFS-induced contraction. Pretreatments with goldfish ghrelin-17 and rat ghrelin did not modify the EFS-induced contraction. The mRNAs of two types of growth hormone secretagogue receptor (GHS R), GHS-R1a-1 and GHS-R1a-2, were detected in the goldfish intestine, and the expression level of GHS-R1a-2 was 4-times higher than that of GHS-R1a-1. The expression levels of GHS-R1a-1 and GHS-R1a-2 in four regions of the goldfish intestine (intestinal bulb, intestine-1, intestine-2 and intestine-3) were almost the same. In conclusion, ghrelin does not affect gastrointestinal contractility of the rainbow trout and goldfish, although GHSR-like receptor/GHS-R1a is expressed entire intestine. These results suggest diversity of ghrelin function in vertebrates. PMID- 22776447 TI - Suppression of premotor cortex disrupts motor coding of peripersonal space. AB - Peripersonal space (PPS) representation depends on the activity of a fronto parietal network including the premotor cortex (PMc) and the posterior parietal cortex (PPc). PPS representation has a direct effect on the motor system: a stimulus activating the PPS around the hand modulates the excitability of hand representation in the primary motor cortex. However, to date, direct information about the involvement of the PMc-PPc network in the motor mapping of sensory events occurring within PPS is lacking. To address this issue, we used a 'perturb and-measure' paradigm based on the combination of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) techniques. Cathodal tDCS was applied to transiently suppress neural activity in PMc, PPc and primary visual cortex (V1; serving as an active control site); single-pulse TMS was used to induce motor-evoked potentials (MEPs) from hand muscles and so to measure the excitability of the hand motor representation. MEPs were compared when a sound was presented either near the hand or at a distance. In experimental sessions performed after sham-tDCS and after tDCS over the control area V1, we found a spatially dependent modulation of the hand motor representation: sounds presented near the hand induced an inhibitory motor response as compared to sounds presented far apart. Critically, this effect was selectively abolished after tDCS suppression of neural activity in PMc, but not when perturbing the activity of PPc. These findings suggest that PMc has a critical role in mapping sensory representations of space onto the motor system. PMID- 22776446 TI - The majority of dorsal spinal cord gastrin releasing peptide is synthesized locally whereas neuromedin B is highly expressed in pain- and itch-sensing somatosensory neurons. AB - BACKGROUND: Itch is one of the major somatosensory modalities. Some recent findings have proposed that gastrin releasing peptide (Grp) is expressed in a subset of dorsal root ganglion (DRG) neurons and functions as a selective neurotransmitter for transferring itch information to spinal cord interneurons. However, expression data from public databases and earlier literatures indicate that Grp mRNA is only detected in dorsal spinal cord (dSC) whereas its family member neuromedin B (Nmb) is highly expressed in DRG neurons. These contradictory results argue that a thorough characterization of the expression of Grp and Nmb is warranted. FINDINGS: Grp mRNA is highly expressed in dSC but is barely detectable in DRGs of juvenile and adult mice. Anti-bombesin serum specifically recognizes Grp but not Nmb. Grp is present in a small number of small-diameter DRG neurons and in abundance in layers I and II of the spinal cord. The reduction of dSC Grp after dorsal root rhizotomy is significantly different from those of DRG derived markers but similar to that of a spinal cord neuronal marker. Double fluorescent in situ of Nmb and other molecular markers indicate that Nmb is highly and selectively expressed in nociceptive and itch-sensitive DRG neurons. CONCLUSION: The majority of dSC Grp is synthesized locally in dorsal spinal cord neurons. On the other hand, Nmb is highly expressed in pain- and itch-sensing DRG neurons. Our findings provide direct anatomic evidence that Grp could function locally in the dorsal spinal cord in addition to its roles in DRG neurons and that Nmb has potential roles in nociceptive and itch-sensitive neurons. These results will improve our understanding about roles of Grp and Nmb in mediating itch sensation. PMID- 22776448 TI - Rapid whole cerebrum myelin water imaging using a 3D GRASE sequence. AB - Myelin water imaging, a magnetic resonance imaging technique capable of resolving the fraction of water molecules which are located between the layers of myelin, is a valuable tool for investigating both normal and pathological brain structure in vivo. There is a strong need for pulse sequences which improve the quality and applicability of myelin water imaging in a clinical setting. In this study, we validated the use of a fast multi echo T(2) relaxation sequence for myelin water imaging. Using a multiple combined gradient and spin echo (GRASE) technique, we attain whole cerebrum myelin water images in under 15 minutes. Region of interest analysis indicates that this fast GRASE imaging sequence produces results which are in good agreement with pure spin echo measurements (R(2)=0.95, p<0.0001). This drastic improvement in speed and brain coverage compared to current spin echo standards will allow increased inclusion of myelin water imaging in neurological research protocols and opens up the possibility of applications in a clinical setting. PMID- 22776449 TI - Deformation-based brain morphometry in rats. AB - Magnetic resonance imaging (MRI)-based morphometry provides in vivo evidence for macro-structural plasticity of the brain. Experiments on small animals using automated morphometric methods usually require expensive measurements with ultra high field dedicated animal MRI systems. Here, we developed a novel deformation based morphometry (DBM) tool for automated analyses of rat brain images measured on a 3-Tesla clinical whole body scanner with appropriate coils. A landmark-based transformation of our customized reference brain into the coordinates of the widely used rat brain atlas from Paxinos and Watson (Paxinos Atlas) guarantees the comparability of results to other studies. For cross-sectional data, we warped images onto the reference brain using the low-dimensional nonlinear registration implemented in the MATLAB software package SPM8. For the analysis of longitudinal data sets, we chose high-dimensional registrations of all images of one data set to the first baseline image which facilitate the identification of more subtle structural changes. Because all deformations were finally used to transform the data into the space of the Paxinos Atlas, Jacobian determinants could be used to estimate absolute local volumes of predefined regions-of interest. Pilot experiments were performed to analyze brain structural changes due to aging or photothrombotically-induced cortical stroke. The results support the utility of DBM based on commonly available clinical whole-body scanners for highly sensitive morphometric studies on rats. PMID- 22776450 TI - Automatic prediction error responses to hands with unexpected laterality: an electrophysiological study. AB - Little is known about how the human brain keeps track of body parts in the visual field. Here we show that unattended images of right/left hands elicit a mismatch response when they violate a regularity established by repeated visual presentations of the other hand. In a visual oddball experiment we found mismatch responses to hands with unexpected laterality (e.g. left versus predicted right hand) in the periphery of the visual field. Unexpected left hands were processed predominantly in the contralateral superior parietal cortex, whereas unexpected right hands evoked differential activity in the contralateral superior parietal, ventral premotor, prefrontal and temporal areas, indicating a more elaborate automatic processing of the dominant hand. The amplitude of the differential activity to the right hand correlated with handedness test scores. Our results reveal the continuous monitoring of the left or right identity of hands, which is prerequisite to the ability to automatically transform observed actions into the observer's ego-centric spatial reference frame. PMID- 22776451 TI - Endotoxin-induced systemic inflammation activates microglia: [11C]PBR28 positron emission tomography in nonhuman primates. AB - Microglia play an essential role in many brain diseases. Microglia are activated by local tissue damage or inflammation, but systemic inflammation can also activate microglia. An important clinical question is whether the effects of systemic inflammation on microglia mediate the deleterious effects of systemic inflammation in diseases such as Alzheimer's dementia, multiple sclerosis, and stroke. Positron Emission Tomography (PET) imaging with ligands that bind to Translocator Protein (TSPO) can be used to detect activated microglia. The aim of this study was to evaluate whether the effect of systemic inflammation on microglia could be measured with PET imaging in nonhuman primates, using the TSPO ligand [(11)C]PBR28. METHODS: Six female baboons (Papio anubis) were scanned before and at 1h and/or 4h and/or 22 h after intravenous administration of E. coli lipopolysaccharide (LPS; 0.1mg/kg), which induces systemic inflammation. Regional time-activity data from regions of interest (ROIs) were fitted to the two-tissue compartmental model, using the metabolite-corrected arterial plasma curve as input function. Total volume of distribution (V(T)) of [(11)C]PBR28 was used as a measure of total ligand binding. The primary outcome was change in V(T) from baseline. Serum levels of tumor necrosis factor alpha (TNFalpha), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) were used to assess correlations between systemic inflammation and microglial activation. In one baboon, immunohistochemistry was used to identify cells expressing TSPO. RESULTS: LPS administration increased [(11)C]PBR28 binding (F(3,6)=5.1, p=.043) with a 29 +/- 16% increase at 1h (n=4) and a 62 +/- 34% increase at 4h (n=3) post-LPS. There was a positive correlation between serum IL 1beta and IL-6 levels and the increase in [(11)C]PBR28 binding. TSPO immunoreactivity occurred almost exclusively in microglia and rarely in astrocytes. CONCLUSION: In the nonhuman-primate brain, LPS-induced systemic inflammation produces a robust increase in the level of TSPO that is readily detected with [(11)C]PBR28 PET. The effect of LPS on [(11)C]PBR28 binding is likely mediated by inflammatory cytokines. Activation of microglia may be a mechanism through which systemic inflammatory processes influence the course of diseases such as Alzheimer's, multiple sclerosis, and possibly depression. PMID- 22776453 TI - Increased sensory feedback in Tourette syndrome. AB - Tourette syndrome (TS) is a neuro-psychiatric disorder being characterized by motor and phonic tics typically preceded by sensory urges. Given the latter the role of the sensory system and sensorimotor interaction in TS has recently gained increased attention. 12 TS patients and 12 matched control subjects performed two tasks, requiring simple finger movements: a Go/NoGo task and a self paced movement task. Neurophysiological data was recorded using magnetoencephalography (MEG). Event related responses around movement onset, i.e. motor field (MF) occurring directly prior to the movement and movement evoked field (MEF) immediately after movement onset were analyzed using dipole modeling. MF peak amplitudes did not differ between groups in either task. In contrast, in both tasks MEF peak amplitudes were increased in TS patients. Moreover, larger MEF amplitudes during self paced movements were inversely correlated with motor tic frequency and severity. Enlarged MEF amplitudes as a marker of early sensory feedback of one's own movements probably represent enlarged sensory input from the periphery resulting from altered subcortical gating. We conclude that TS patients exhibit altered sensory-motor processing involved in voluntary movement control, which might also be successful in tic control. PMID- 22776452 TI - Visual short-term memory: activity supporting encoding and maintenance in retinotopic visual cortex. AB - Recent studies have demonstrated that retinotopic cortex maintains information about visual stimuli during retention intervals. However, the process by which transient stimulus-evoked sensory responses are transformed into enduring memory representations is unknown. Here, using fMRI and short-term visual memory tasks optimized for univariate and multivariate analysis approaches, we report differential involvement of human retinotopic areas during memory encoding of the low-level visual feature orientation. All visual areas show weaker responses when memory encoding processes are interrupted, possibly due to effects in orientation sensitive primary visual cortex (V1) propagating across extrastriate areas. Furthermore, intermediate areas in both dorsal (V3a/b) and ventral (LO1/2) streams are significantly more active during memory encoding compared with non memory (active and passive) processing of the same stimulus material. These effects in intermediate visual cortex are also observed during memory encoding of a different stimulus feature (spatial frequency), suggesting that these areas are involved in encoding processes on a higher level of representation. Using pattern classification techniques to probe the representational content in visual cortex during delay periods, we further demonstrate that simply initiating memory encoding is not sufficient to produce long-lasting memory traces. Rather, active maintenance appears to underlie the observed memory-specific patterns of information in retinotopic cortex. PMID- 22776454 TI - Hypothalamic-pituitary-adrenal axis tonus is associated with hippocampal microstructural asymmetry. AB - It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is growing evidence for hemispheric lateralization in brain systems regulating arousal and emotion. Here we tested the hypotheses that individual variations in basal morning and afternoon/evening cortisol levels would be associated with the degree of hemispheric asymmetry in hippocampal microstructure. Fifty healthy adults aged 19 to 86 years were included in the analyses. Diffusion-weighted imaging was acquired from all subjects. Hippocampal mean diffusivity (MD) and volume was extracted. Cortisol measures were based on 5 morning and 3 afternoon/evening saliva samples. Higher left relative to right hippocampus MD was associated with higher basal cortisol levels. Associations were anatomically specific and not attributable to hippocampal volume asymmetry. No correlation between hippocampal volume and MD was observed, suggesting that MD and volume index distinct biological properties of the hippocampus. Observed associations raise a number of possibilities, among them an asymmetric role of the hippocampus on HPA-axis regulation, or conversely, that individual variations in secreted cortisol, perhaps associated with stress, may have lateralized effects on hippocampal microstructure. Our results point to an important relationship between the limbic system and neuroendocrine function in terms of left-right asymmetries, raising additional questions about how the limbic system is related to neuroendocrine functions. PMID- 22776455 TI - The impact of aging on gray matter structural covariance networks. AB - Previous anatomical volumetric studies have shown that healthy aging is associated with gray matter tissue loss in specific cerebral regions. However, these studies may have potentially missed critical elements of age-related brain changes, which largely exist within interrelationships among brain regions. This magnetic resonance imaging research aims to assess the effects of aging on the organization of gray matter structural covariance networks. Here, we used voxel based morphometry on high-definition brain scans to compare the patterns of gray matter structural covariance networks that sustain different sensorimotor and high-order cognitive functions among young (n=88, mean age=23.5+/-3.1 years, female/male=55/33) and older (n=88, mean age=67.3+/-5.9 years, female/male=55/33) participants. This approach relies on the assumption that functionally correlated brain regions show correlations in gray matter volume as a result of mutually trophic influences or common experience-related plasticity. We found reduced structural association in older adults compared with younger adults, specifically in high-order cognitive networks. Major differences were observed in the structural covariance networks that subserve the following: a) the language related semantic network, b) the executive control network, and c) the default mode network. Moreover, these cognitive functions are typically altered in the older population. Our results indicate that healthy aging alters the structural organization of cognitive networks, shifting from a more distributed (in young adulthood) to a more localized topological organization in older individuals. PMID- 22776457 TI - Evidence for structural plasticity in humans: comment on Thomas and Baker (2012). AB - Thomas and Baker (2012) have provided a balanced and critical review of the scientific evidence claiming that training interventions have the capacity to alter the structural morphology of the brain. Here I provide some additional considerations when reading and interpreting both the review and the original empirical articles. Research proposing to examine the capacity for structural brain plasticity needs to contemplate methodological issues and factors that could moderate or mask potentially interesting effects. Overall, although this area of research is in need of circumspection, it also could have transformative implications if structural brain plasticity in humans is possible. PMID- 22776458 TI - Developmental changes in patterns of brain activity associated with moment-to moment adjustments in control. AB - The current study investigated age-related changes in patterns of brain activity associated with moment-to-moment adjustments in control through the use of fMRI. Fifty-eight participants ranging continuously in age from 9 to 32 years were scanned as they performed a task in which the need for rapid adjustments in control was greater in one condition than another. Despite comparable behavioral performance across ages, moment-to-moment adjustments were associated with stronger engagement of anterior cingulate, anterior insula, lateral prefrontal cortex and the intraparietal sulcus in older than in younger participants. The findings confirm the importance of cingulo-insular and fronto-parietal cortices for moment-to-moment adjustments in control, and suggest continuous increases in the utilization of these networks over development. PMID- 22776456 TI - Selection and inhibition mechanisms for human voluntary action decisions. AB - One can choose between action alternatives that have no apparent difference in their outcomes. Such voluntary action decisions are associated with widespread frontal-parietal activation, and a tendency to inhibit the repetition of a previous action. However, the mechanism of initiating voluntary actions and the functions of different brain regions during this process remains largely unknown. Here, we combine computational modeling and functional magnetic resonance imaging to test the selection and inhibition mechanisms that mediate trial-to-trial voluntary action decisions. We fitted an optimized accumulator model to behavioral responses in a finger-tapping task in which participants were instructed to make chosen actions or specified actions. Model parameters derived from each individual were then applied to estimate the expected accumulated metabolic activity (EAA) engaged in every single trial. The EAA was associated with blood oxygenation level-dependent responses in a decision work that was maximal in the supplementary motor area and the caudal anterior cingulate cortex, consistent with a competitive accumulation-to-threshold mechanism for action decision by these regions. Furthermore, specific inhibition of the previous action's accumulator was related to the suppression of response repetition. This action-specific inhibition correlated with the activity of the right inferior frontal gyrus, when the option to repeat existed. Our findings suggest that human voluntary action decisions are mediated by complementary processes of intentional selection and inhibition. PMID- 22776459 TI - Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment. AB - Abnormalities of functional connectivity in the default mode network (DMN) recently have been reported in patients with amnestic mild cognitive impairment (aMCI), Alzheimer's disease (AD) or other psychiatric diseases. As such, these abnormalities may be epiphenomena instead of playing a causal role in AD progression. To date, few studies have investigated specific brain networks, which extend beyond the DMN involved in the early AD stages, especially in aMCI. The insula is one site affected by early pathological changes in AD and is a crucial hub of the human brain networks. Currently, we explored the contribution of the insula networks to cognitive performance in aMCI patients. Thirty aMCI and 26 cognitively normal (CN) subjects participated in this study. Intrinsic connectivity of the insula networks was measured, using the resting-state functional connectivity fMRI approach. We examined the differential connectivity of insula networks between groups, and the neural correlation between the altered insula networks connectivity and the cognitive performance in aMCI patients and CN subjects, respectively. Insula subregional volumes were also investigated. AMCI subjects, when compared to CN subjects, showed significantly reduced right posterior insula volumes, cognitive deficits and disrupted intrinsic connectivity of the insula networks. Specifically, decreased intrinsic connectivity was primarily located in the frontal-parietal network and the cingulo-opercular network, including the anterior prefrontal cortex (aPFC), anterior cingulate cortex, operculum, inferior parietal cortex and precuneus. Increased intrinsic connectivity was primarily situated in the visual-auditory pathway, which included the posterior superior temporal gyrus and middle occipital gyrus. Conjunction analysis was performed; and significantly decreased intrinsic connectivity in the overlapping regions of the anterior and posterior insula networks, including the bilateral aPFC, left dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, and anterior temporal pole was found. Furthermore, the disrupted intrinsic connectivity was associated with episodic memory (EM) deficits in the aMCI patients and not in the CN subjects. These findings demonstrated that the functional integration of the insula networks plays an important role in the EM process. They provided new insight into the neural mechanism underlying the memory deficits in aMCI patients. PMID- 22776461 TI - Nucleus accumbens response to food cues predicts subsequent snack consumption in women and increased body mass index in those with reduced self-control. AB - Individuals have difficulty controlling their food consumption, which is due in part to the ubiquity of tempting food cues in the environment. Individual differences in the propensity to attribute incentive (motivational) salience to and act on these cues may explain why some individuals eat more than others. Using fMRI in healthy women, we found that food cue related activity in the nucleus accumbens, a key brain region for food motivation and reward, was related to subsequent snack food consumption. However, both nucleus accumbens activation and snack food consumption were unrelated to self-reported hunger, or explicit wanting and liking for the snack. In contrast, food cue reactivity in the ventromedial prefrontal cortex was associated with subjective hunger/appetite, but not with consumption. Whilst the food cue reactivity in the nucleus accumbens that predicted snack consumption was not directly related to body mass index (BMI), it was associated with increased BMI in individuals reporting low self control. Our findings reveal a neural substrate underpinning automatic environmental influences on consumption in humans and demonstrate how self control interacts with this response to predict BMI. Our data provide support for theoretical models that advocate a 'dual hit' of increased incentive salience attribution to food cues and poor self-control in determining vulnerability to overeating and overweight. PMID- 22776462 TI - Striatal dopamine D2/D3 receptor binding in pathological gambling is correlated with mood-related impulsivity. AB - Pathological gambling (PG) is a behavioural addiction associated with elevated impulsivity and suspected dopamine dysregulation. Reduced striatal dopamine D(2)/D(3) receptor availability has been reported in drug addiction, and may constitute a premorbid vulnerability marker for addictive disorders. The aim of the present study was to assess striatal dopamine D(2)/D(3) receptor availability in PG, and its association with trait impulsivity. Males with PG (n=9) and male healthy controls (n=9) underwent [11C]-raclopride positron emission tomography imaging and completed the UPPS-P impulsivity scale. There was no significant difference between groups in striatal dopamine D(2)/D(3) receptor availability, in contrast to previous reports in drug addiction. However, mood-related impulsivity ('Urgency') was negatively correlated with [11C]-raclopride binding potentials in the PG group. The absence of a group difference in striatal dopamine binding implies a distinction between behavioural addictions and drug addictions. Nevertheless, our data indicate heterogeneity in dopamine receptor availability in disordered gambling, such that individuals with high mood-related impulsivity may show differential benefits from dopamine-based medications. PMID- 22776460 TI - Development of BOLD signal hemodynamic responses in the human brain. AB - In the rodent brain the hemodynamic response to a brief external stimulus changes significantly during development. Analogous changes in human infants would complicate the determination and use of the hemodynamic response function (HRF) for functional magnetic resonance imaging (fMRI) in developing populations. We aimed to characterize HRF in human infants before and after the normal time of birth using rapid sampling of the blood oxygen level dependent (BOLD) signal. A somatosensory stimulus and an event related experimental design were used to collect data from 10 healthy adults, 15 sedated infants at term corrected post menstrual age (PMA) (median 41+1 weeks), and 10 preterm infants (median PMA 34+4 weeks). A positive amplitude HRF waveform was identified across all subject groups, with a systematic maturational trend in terms of decreasing time-to-peak and increasing positive peak amplitude associated with increasing age. Application of the age-appropriate HRF models to fMRI data significantly improved the precision of the fMRI analysis. These findings support the notion of a structured development in the brain's response to stimuli across the last trimester of gestation and beyond. PMID- 22776464 TI - Adipose-derived stem cells can abrogate chemical-induced liver fibrosis and facilitate recovery of liver function. AB - Adipose-derived stem cells (ADSCs) are easy to harvest and have the ability for self-renewal and to differentiate into various cell types, including those of the hepatic lineage. Studies on the use of ADSCs for liver transplantation are, however, limited. The objective of this study was to investigate the feasibility of using human ADSCs and to better understand their mechanism of action for the repair of liver damage in a thioacetamide (TAA)-induced model of chronic liver damage in the rat. To induce liver damage, 200 mg/kg TAA was injected intraperitoneally into Wistar rats every 3 days for 60 days. For cell therapy, 1 * 10(6) human ADSCs suspended in 300 MUl of phosphate-buffered saline were transplanted into each experimental rat by direct liver injection. Immunohistochemistry showed that the transplanted ADSCs differentiated into albumin- and alpha-fetoprotein-secreting liver-like cells 1 week after transplantation. In addition, liver function recovered significantly, as determined by biochemical analyses that analyzed total bilirubin, prothrombin time, and albumin levels. The Metavir score, derived from histopathological analysis, also showed a significant decrease in liver fibrosis and inflammatory activity after ADSC transplantation. Finally, we found a reduction in the expression of alpha-smooth muscle actin, a marker of hepatic stellate cells, which produce collagen fiber, and an increase in the expression of matrix metalloproteinase-9, which degrades collagen fiber, after ADSC transplantation. These findings are consistent with abrogation of liver fibrosis in the ADSC therapy group. Consequently, these results suggest that ADSC transplantation may facilitate recovery from chronic liver damage and thus may have clinical applications. PMID- 22776463 TI - Reduction of physiological noise with independent component analysis improves the detection of nociceptive responses with fMRI of the human spinal cord. AB - The evaluation of spinal cord neuronal activity in humans with functional magnetic resonance imaging (fMRI) is technically challenging. Major difficulties arise from cardiac and respiratory movement artifacts that constitute significant sources of noise. In this paper we assessed the Correction of Structured noise using spatial Independent Component Analysis (CORSICA). FMRI data of the cervical spinal cord were acquired in 14 healthy subjects using gradient-echo EPI. Nociceptive electrical stimuli were applied to the thumb. Additional data with short TR (250 ms, to prevent aliasing) were acquired to generate a spatial map of physiological noise derived from Independent Component Analysis (ICA). Physiological noise was subsequently removed from the long-TR data after selecting independent components based on the generated noise map. Stimulus evoked responses were analyzed using the general linear model, with and without CORSICA and with a regressor generated from the cerebrospinal fluid region. Results showed higher sensitivity to detect stimulus-related activation in the targeted dorsal segment of the cord after CORSICA. Furthermore, fewer voxels showed stimulus-related signal changes in the CSF and outside the spinal region, suggesting an increase in specificity. ICA can be used to effectively reduce physiological noise in spinal cord fMRI time series. PMID- 22776465 TI - Intelligence quotient in childhood and the risk of illegal drug use in middle age: the 1958 National Child Development Survey. AB - PURPOSE: High childhood IQ test scores have been associated with increased alcohol dependency and use in adult life, but the relationship between childhood IQ and illegal drug use in later life is unclear. METHODS: Participants were 6713 members of the 1958 National Child Development Survey whose IQ was assessed at 11 years and had their lifetime illegal drug use measured at 42 years of age. RESULTS: In analyses adjusted for a range of covariates, a 1 SD (15-point) increase in IQ scores was associated with an increased risk of illegal drug use in women: ever using cannabis (odds ratio [OR], 1.30; 95% confidence interval [95% CI], 1.16-1.45), cocaine (OR, 1.66; 95% CI, 1.21-2.27), amphetamines (OR, 1.50; 95% CI, 1.22-1.83), amyl nitrate (OR, 1.79; 95% CI, 1.30-2.46) and "magic mushrooms" (OR, 1.52; 95% CI, 1.18-1.98). Associations were of lower magnitude in men. CONCLUSIONS: In this cohort, high childhood IQ was related to illegal drug use in adulthood. PMID- 22776466 TI - Evaluation of the effect of appropriate antimicrobial therapy on mortality associated with Acinetobacter nosocomialis bacteraemia. AB - Appropriate antimicrobial therapy is effective for severe infections caused by Acinetobacter baumannii, but efficacy for other Acinetobacter species remains to be established. The current study was designed to determine whether appropriate antimicrobial therapy reduces the mortality of patients with Acinetobacter nosocomialis bacteraemia. A 9-year retrospective study of 266 patients with monomicrobial A. nosocomialis bacteraemia was conducted at a large teaching hospital in Taiwan. Multivariable analysis was performed to evaluate the impact on 14-day mortality according to clinical characteristics, severity of disease and use of appropriate antimicrobial therapy. The influence of APACHE II score on the impact of appropriate antimicrobial therapy was analysed by including an interaction term. The overall 14-day mortality was 9.4%. Multivariable analysis revealed that APACHE II score was the only factor significantly associated with mortality (odds ratio, 1.18; 95% confidence interval, 1.11-1.25; p <0.001). Appropriate antimicrobial therapy was not associated with reduced mortality regardless of disease severity. In the subgroup analyses in patients with different clinical conditions, APACHE II score was consistently an independent factor for 14-day mortality, and appropriate antimicrobial therapy did not affect the mortality in any group. In conclusion, severity of disease, based on the APACHE II score, was the independent risk factor for 14-day mortality for patients with monomicrobial A. nosocomialis bacteraemia, even in different clinical conditions. In contrast, appropriate antimicrobial therapy did not reduce the 14-day mortality. The result highlighted a different effect of appropriate antimicrobial therapy on infections caused by two phenotypically undifferentiated Acinetobacter. PMID- 22776467 TI - Age at onset of rheumatoid arthritis: association with polymorphisms in the vascular endothelial growth factor A(VEGFA) gene and an intergenic locus between matrix metalloproteinase (MMP) 1 and 3 genes. AB - OBJECTIVES: The present paper aims to investigate whether polymorphisms in the vascular endothelial growth factor A (VEGFA) gene and the loci of matrix metalloproteinase (MMP) 1 and 3 genes are associated with age at onset of RA. METHODS: A sample of 413 hospital-based RA patients of Caucasian origin was studied. Common single-nucleotide polymorphisms (SNP) with likely importance were typed, including rs699947, rs833061, rs2010963 and rs3025039 in VEGFA, and rs1799750 in the MMP1 gene, rs3025058, rs679620 in the MMP3 gene and rs495366 located within the region between the MMP1 and MMP3 genes. Age at onset of RA was obtained on each patient. Demographic variables, smoking information, and a core set of clinical characteristics measured at recruitment were recorded. Hazard ratios (HR) that measured the effect size of genetic risk on age at RA onset were computed using Cox regression models. RESULTS: The T allele at rs3025039 was associated with an increased risk of early onset (HR=1.25 [95% CI 1.0-1.58] for the risk over time; HR=1.84 [95% CI 1.20-2.83] for the risk of onset <40 years old). The AA genotype at rs495366 was also associated with an increased risk (HR=1.92 [95% CI 1.27-2.89] over time; HR=2.54 [95% CI 1.30-4.95] for onset <40 years old). These associations were independent of other risk factors such as sex, smoking and anti-CCP status. CONCLUSIONS: Polymorphisms in the VEGFA gene and the MMP1-3 intergenic locus may influence age at onset of RA. PMID- 22776468 TI - Presentations delivered during the 12th Symposium of the International Society for Invertebrate Neurobiology. Preface. PMID- 22776470 TI - The anti-intuitive visual system of the honey bee. AB - Because bees fly around, visit flowers and chase mates, we conclude intuitively that they see things as we do. But their vision is unexpectedly different, so we say it is anti-intuitive. Detailed tests have demonstrated separate detectors for modulation of blue and green receptors, edge orientation (green only), and areas of black. The edge detectors are about 3 degrees across, independent, and not re assembled to make lines, shapes or textures. Instead, the detectors of each type are summed quantitatively to form cues in each local region with an order of preference for learning the cues. Trained bees remember the positions of the total modulation (preferred), the average edge orientation, areas of black or colour, and positions of hubs of radial and circular edges in each local region, but not the original responses, so the pattern is lost. When presented with a yellow spot on a blue background with no UV reflected, the preferred cue is not the colour, but a measure of the modulation detected by the green and separately by the blue receptors. PMID- 22776469 TI - Phylogenomics meets neuroscience: how many times might complex brains have evolved? AB - The origin of complex centralized brains is one of the major evolutionary transitions in the history of animals. Monophyly (i.e. presence of a centralized nervous system in urbilateria) vs polyphyly (i.e. multiple origins by parallel centralization of nervous systems within several lineages) are two historically conflicting scenarios to explain such transitions. However, recent phylogenomic and cladistic analysis suggests that complex brains may have independently evolved at least 9 times within different animal lineages. Indeed, even within the phylum Mollusca cephalization might have occurred at least 5 times. Emerging molecular data further suggest that at the genomic level such transitions might have been achieved by changes in expression of just a few transcriptional factors - not surprising since such events might happen multiple times over 700 million years of animal evolution. Both cladistic and genomic analyses also imply that neurons themselves evolved more than once. Ancestral polarized secretory cells were likely involved in coordination of ciliated locomotion in early animals, and these cells can be considered as evolutionary precursors of neurons within different lineages. Under this scenario, the origins of neurons can be linked to adaptations to stress/injury factors in the form of integrated regeneration-type cellular response with secretory signaling peptides as early neurotransmitters. To further reconstruct the parallel evolution of nervous systems genomic approaches are essential to probe enigmatic neurons of basal metazoans, selected lophotrochozoans (e.g. phoronids, brachiopods) and deuterostomes. PMID- 22776471 TI - Plausible neural circuitry for photoperiodism in the blow fly, Protophormia terraenovae. AB - Photoperiodism is important for seasonal adaptation in insects. Although photoreceptors and endocrine outputs for photoperiodism have been investigated, its neural mechanisms are less studied. This paper proposes three groups of neurons involved in photoperiodic control of adult diapause in the blow fly, Protophormia terraenovae. Ablation experiments showed that pars lateralis neurons in the dorsal protocerebrum are important for diapause induction under short-days and low temperature, the pars intercerebralis neurons for ovarian development under long-days and high temperature. When regions containing pigment-dispersing factor and PERIOD immunoreactive s-LNvs were bilaterally ablated, flies became arrhythmic in locomotor activities, and did not discriminate photoperiod for diapause induction, suggesting that s-LNvs are important for circadian rhythm and photoperiodism. In the s-LNvs, PERIOD-immunoreactivity in the nucleus was highest at 12 h after lights-off and lowest 12 h after lights-on regardless of photoperiod. Thus, as in D. melanogaster, it is possible that PERIOD nuclear translocation entrains to photoperiod, and day-length information seems to be encoded in s-LNvs. Immunoelectronmicroscopy revealed synaptic connections from s LNvs to the pars lateralis neurons, suggesting that circadian clock neurons, s LNvs, are involved in time measurements and may synaptically signal day-length information to the pars lateralis neurons. PMID- 22776472 TI - SIFamide in the brain of the sphinx moth, Manduca sexta. AB - SIFamides form a group of highly conserved neuropeptides in insects, crustaceans, and chelicerates. Beyond their biochemical commonalities, the neuroanatomical distribution of SIFamide in the insect nervous system also shows a remarkable degree of conservation. Thus, expression of SIFamide has been found to be restricted to four neurons of the pars intercerebralis in different holometabolous species. By means of immunohistological stainings, we here show that in Manduca sexta, those four cells are complemented by additional immunoreactive cells located in the vicinity of the mushroom body calyx. Immunopositive processes form arborizations throughout the brain, innervating major neuropils like the antennal lobes, the central complex, and the optic neuropils. PMID- 22776473 TI - Identification and expression analyses of a novel serotonin receptor gene, 5 HT2beta, in the field cricket, Gryllus bimaculatus. AB - Biogenic amine serotonin (5-HT) modulates various aspects of behaviors such as aggressive behavior and circadian behavior in the cricket. In our previous report, in order to elucidate the molecular basis of the cricket 5-HT system, we identified three genes involved in 5-HT biosynthesis, as well as four 5-HT receptor genes (5-HT1A, 5-HT1B, 5-HT2alpha, and 5-HT7) expressed in the brain of the field cricket Gryllus bimaculatus DeGeer [7]. In the present study, we identified Gryllus 5-HT2beta gene, an additional 5-HT receptor gene expressed in the cricket brain, and examined its tissue-specific distribution and embryonic stage-dependent expression. Gryllus 5-HT2beta gene was ubiquitously expressed in the all examined adult tissues, and was expressed during early embryonic development, as well as during later stages. This study suggests functional differences between two 5-HT2 receptors in the cricket. PMID- 22776474 TI - Octopaminergic system in the brain controls aggressive motivation in the ant, Formica japonica. AB - The ant, Formica japonica, is polyphagous and workers hunt other insects as foods. In this study, interspecific aggression was examined in the workers and queens. Behavior experiments demonstrated that interspecific aggressiveness was significantly higher in workers than queens. Workers showed predatory aggressive behavior towards crickets, on the other hand, queens elicited threat behavior but they didn't attack crickets. In order to investigate neuronal mechanisms underlying regulation of aggressive motivation, the role of biogenic amine in the brain in evoking aggressive behavior was examined by measuring biogenic amine using high-performance liquid chromatography (HPLC) with electrochemical detection (ECD). No significant difference in the octopamine (OA) level was found between workers and queens, but the level of N-acetyloctopamine (NacOA) in the brain of queens was significantly higher than that of workers. This study suggests that OAergic system in the brain must involve in controlling aggressive motivation in the ants. PMID- 22776475 TI - Aggressive behavior of the white-eye mutant crickets, Gryllus bimaculatus. AB - Aggressive behavior of white-eye mutant crickets was investigated and compared with that of wild-type crickets. In the dark, wild-type pairs performed long lasting fights with significantly higher aggressive levels compared to those in the light. In contrast, fights between two white-eye mutants were not significantly different with those between two wild-type crickets both in duration and the aggressive levels. Ethograms of aggressive behavior showed that the mutants could show typical sequentially escalating fight with the same behavioral categories as the wild-type crickets. These results indicate that the white-eye mutants are able to express normal aggressive behavior. PMID- 22776476 TI - Mathematical analysis of the honeybee waggle dance. AB - A honeybee informs her nestmates of the location of a flower by doing a waggle dance. The waggle dance encodes both the direction of and distance to the flower from the hive. To reveal how the waggle dance benefits the colony, we created a Markov model of bee foraging behavior and performed simulation experiments by incorporating the biological parameters that we obtained from our own observations of real bees as well as from the literature. When two feeders were each placed 400 m away from the hive in different directions, a virtual colony in which honeybees danced and correctly transferred information (a normal, real bee colony) made significantly greater numbers of successful visits to the feeders compared to a colony with inaccurate information transfer. Howerer, when five feeders were each located 400 m from the hive, the inaccurate information transfer colony performed better than the normal colony. These results suggest that dancing's ability to communicate accurate information depends on the number of feeders. Furthermore, because non-dancing colonies always made significantly fewer visits than those two colonies, we concluded that dancing behavior is beneficial for hives' ability to visit food sources. PMID- 22776477 TI - Behavioral evidence for internal factors affecting duration of conglobation in pill bugs (Armadillidium vulgare, Isopoda, Crustacea). Short communication. AB - Pill bugs individually walked an experimental pathway, then were induced to conglobate with a puff of air. After recovering, they were stimulated again. Sixty of 80 pill bugs conglobated both times, first moving either antennae (A) or legs (L) during recovery. Both AA and LL groups showed a significant positive correlation between first (t1) and second (t2) conglobation times. In the AL group, pathway locomotion time (t0) was significantly positively correlated to both t1 and t2. We conclude that pill bugs determine conglobation time based partly on their previous states. PMID- 22776478 TI - Some aspects of the immunolocalization of FMRFamide in the nervous system of turbellarians, Polycelis tenuis and Girardia tigrina. Short communication. AB - The details of the morphology of the nervous system has been investigated in two turbellarian species Polycelis tenuis and Girardia tigrina using confocal laser scanning microscopy and immunostaining to neuropeptide FMRFamide. Abundant FMRFamide immunoreactivity (FMRF-IR) has been observed in central and peripheral nervous systems of both species. Intensive staining has been found in the sensory elements: cells and fibres surrounded the mouth opening, in the fibres enclosed the photoreceptors, triangular auricles in the head region of G. tigrina. The possible function of FMRF-IR neurons in the realization of sensory function in turbellarians is discussed. PMID- 22776479 TI - The structure of Archiannelid Dinophilus gyrociliatus ventral nerve cords. AB - Dinophilus gyrociliatus is a typical representative of the synthetic group Archiannelida. Here we describe the structure of Dinophilus young adults ventral nerve cords. Five nerve cords, irregular commissures and intersegmental nerves are revealed by tubulin and FMRFamide immunostaining. 5-HT-stainning marks the complex varicose nerve plexus with numerous irregularly distributed small perikarya. Four nerve cords and solitary cell bodies occur after clyoxylic induced reaction for catecholamines visualization. Altogether, our results indicated that morphology of Dinophilus ventral nerve cords differs from the Polychaetes archetype in many respects. PMID- 22776480 TI - GABAergic effects on the slow oscillatory neural activities in the procerebrum of Limax valentianus. Short communication. AB - We examined GABAergic modulation on "slow" oscillation (<1.0 Hz) of the procerebrum in the terrestrial mollusk, Limax valentianus. Short application of GABA-receptor agonists slightly increased the frequency of a periodic oscillation in the procerebrum, whereas persistent application decreased it. GABA-receptor antagonists decreased the oscillatory frequency. The GABA-like immunoreactivities were found in the neuropil and the cell body layers of the procerebrum. Because GABAergic inhibition is known to be essential for the generation of "fast" synchronous neuronal oscillation in the CNSs in othre many animals, our present findings are first evidence suggesting that GABA modulates 'slow' oscillation in the CNS. PMID- 22776481 TI - The 5-HT immunoreactive innervation of the Helix procerebrum. AB - In the procerebrum of terrestrial snails, 5-HT is a key modulatory substance of the generation of synchronous oscillatory activity and odor learning capability. In this study, we have analyzed the characteristics of the 5-HT-immunoreactive (5 HT-IR) innervation of the distinct anatomical regions of the procerebrum of Helix pomatia, applying correlative light- and electron microscopic immunocytochemistry. A dense network of 5-HT-IR innervation was demonstrated in the cell body layer, meanwhile a varicose fiber system of different density occurred in the different neuropil regions. At the ultrastructural level, labeled varicosities were found to contact both procerebral cell bodies, and different unlabeled axon profiles in the neuropils. The labeled structures established mostly close non-specialized membrane contacts with the postsynaptic profiles. The overall dense distribution of 5-HT-IR innervation supports a general modulatory role of 5-HT in processing different olfactory events. PMID- 22776482 TI - Immunodetection and localization of nitric oxide synthase in the olfactory center of the terrestrial snail, Helix pomatia. AB - The procerebrum of stylommatophoran snails produces nitric oxide (NO)-modulated oscillatory local field potentials which are considered the basis of olfactory information processing. Although the function of NO is well characterized in the PC, the identification and distribution of NO synthase (NOS) has not known completely. In the present study, applying a mammalian anti-NOS antibody, a 170 kDa molecular weight NOS-like protein was demonstrated in the procerebrum homogenate of Helix pomatia. NOS-like immunolabeling of the globuli cells, the internal and terminal neuropils displayed an identical distribution compared to that of NADPH-diaphorase reactive material, confirming the specificity of immunohistochemistry. The detailed characteristics of the immunostaining (different intensity of the neural perikarya, a gradual appearance in the terminal neuropil and in the axon bundles of the tentacular nerve, as well as an intense, homogeneous distribution of NOS-like immunoreactivity in the internal neuropil) suggest that NOS is expressed constitutively, maintaining a high level of the enzyme in neuropil areas. NOS accumulation in the internal neuropil suggests that NO plays an important role in delivering olfactory signals extrinsic to the procerebrum, and integrating them with other sensory modalities, respectively. Our results are the first, demonstrating unequivocally the presence of NOS and resolving its differential distribution in the Helix procerebrum. PMID- 22776483 TI - High resolution spatial distribution of neuropeptides by MALDI imaging mass spectrometry in the terrestrial snail, Helix pomatia. AB - Imaging mass spectrometry (IMS) is a powerful technique that combines the chemical and spatial analysis of surface materials. It allows spatial localization of peptides, proteins or lipids that are recorded in parallel without the need of a label. It is currently one of the most rapidly developing techniques in the proteomics toolbox. In the present study, accurate mass matrix assisted laser desorption/ionization imaging mass spectrometry (MALD IMS) was used for direct molecular mapping of nervous tissue at micrometer spatial resolution. Cryosections of the whole brain of the terrestrial snail, Helix pomatia, were placed on indium-tin-oxide (ITO)-coated conductive glass slides and covered with a thin layer of alpha-cyano-4-hydroxycinnamic acid (CHCA) matrix by electro spray deposition. High-resolution molecular ion maps of well-known neuropeptides, such as FMRFamide were constructed. FMRFamide is known to exert powerful modulatory effect on synaptic transmission in molluscs. FMRFamide was predominantly localized in the cluster of neurons in the pro-, meso- and postcerebral regions of cerebral ganglia, pedal ganglia and right parietal ganglia of the central nervous system. Our present study, using MALDI IMS confirmed the distribution of FMRFamide containing cells in the Helix central nervous system previously detected by antibody dependent immunohistochemistry. PMID- 22776484 TI - Novel triplet of flexor muscles in the posterior tentacles of the snail, Helix pomatia. AB - The anatomy of three novel flexor muscles in the posterior tentacles of Helix pomatia is described. The muscles originate from the ventral side of the sensory pad and are anchored at different sites in the base of the tentacle stem. The muscles span the tentacle and always take the length of the stem which depends on the rate of tentacle protrusion indicating that the muscles are both contractile and extremely stretchable. The three anchoring points at the base of the stem determine three space axes along which the contraction of a muscle or the synchronous contraction of the muscles can move the tentacle in space. PMID- 22776486 TI - Multistable coordination of feeding motor rhythms in semi-intact preparation of Lymnaea stagnalis. Short communication. AB - It is well known that most rhythm-generating neuronal ensembles are multifunctional and can generate different motor rhythms in different contexts. This implies that coordination of multifunctional networks must also be flexible or multistable. Coordination of radula movements and gut contractions was studied in semi-intact preparations of L. stagnalis using video registration and an event recorder. Several context-dependent stable variants of radula-gut coordination were detected. Our data suggest that this preparation is a promising model for studying mechanisms of multistable motor rhythm coordination. PMID- 22776485 TI - Morphology, ultrastructure and contractile properties of muscles responsible for superior tentacle movements of the snail. AB - Bending, twitching and quivering are different types of tentacle movements observed during olfactory orientation of the snail. Three recently discovered special muscles, spanning along the length of superior tentacles from the tip to the base, seem to be responsible for the execution of these movements. In this study we have investigated the ultrastructure, contractile properties and protein composition of these muscles. Our ultrastructural studies show that smooth muscle fibers are loosely embedded in a collagen matrix and they are coupled with long sarcolemma protrusions. The muscle fibers apparently lack organized SR and transverse tubular system. Instead subsarcolemmal vesicles and mitochondria have been shown to be possible Ca2+ pools for contraction. It was shown that external Ca2+ is required for contraction elicited by high (40 mM) K+ or 10-4 M ACh. Caffeine (5 mM) induced contraction in Ca2+-free solution suggesting the presence of a substantial intracellular Ca2+ pool. High-resolution electrophoretic analysis of columellar and tentacular muscles did not reveal differences in major contractile proteins, such as actin, myosin and paramyosin. Differences were observed however in several bands representing presumably regulatory enzymes. It is concluded that, the ultrastructural, biochemical and contractile properties of the string muscles support their special physiological function. PMID- 22776487 TI - Potassium channels in the Helix central nervous system: preliminary immunohistochemical studies. Short communication. AB - Distribution of the potassium channel of Kv4.3 type was investigated in the central nervous system (CNS) of Helix pomatia by immunohistochemistry. Immunopositive neurons were found widely distributed in the CNS, present mostly in smaller groups in the different central ganglia but not in the visceral ganglion. Labeled fibers were characteristic for not only the neuropils of all ganglia but also the connective tissue sheath around the CNS and the aorta wall were richly innervated. Western blot analysis revealed a clear identity with the mammalian Kv4.3 subunit, suggesting an evolutionary conserved structure of this channel type. Our preliminary results provide a steady basis for further experiments aiming partly at the identification of other potassium channel types and partly the ultrastructural localization of Kv4.3. PMID- 22776488 TI - Immunological and pharmacological identification of the dopamine D1 receptor in the CNS of the pond snail, Lymnaea stagnalis. AB - We investigated the presence and distribution of the D1 dopamine receptor in the CNS of Lymnaea stagnalis applying immunobloting and immunocytochemistry. We also investigated the effect of dopamine as well as the specific D1 receptor blocker, SCH23390, on the firing activity of the feeding modulator serotonergic neuron, CGC, which displayed D1 immunoreactivity. Immunoblot experiments showed one specifically labeled band with 62 kDa mw which is close to that of the mammalian D1 receptor. Neurons displaying D1-like immunoreactivity can be observed in each ganglion of the CNS but particularly in the pedal ganglia which are the center for locomotion. Dopamine regularly evokes burst activity in the serotonergic CGC at 1 mM and this effect could be antagonized by SCH23390. These observations suggest that a D1-like receptor molecule is present in the CNS of Lymnaea. PMID- 22776489 TI - Neurotoxic effects evoked by cyanobacterial extracts suggest multiple receptors involved in electrophysiological responses of molluscan (CNS, heart) models. AB - The responses of the snail central neurons (Helix pomatia, Lymnaea stagnalis) and the isolated Helix heart were characterized evoked by cyanobacterial extracts (Cylindrospermopsis raciborskii ACT strains) isolated from Lake Balaton (Hungary). The nicotinergic acetylcholine (ACh) receptors in the CNS (both excitatory and inhibitory) were blocked by the extracts of ACT 9502 and ACT 9505 strains and the anatoxin- a (homoanatoxin-a) producing reference strain of Oscillatoria sp. (PCC 6506), similar to the inhibitory effects of the pure anatoxin-a. The enhancement of the ACh responses by the ACT 9504 extract suggests additional, probably acetylcholine esterase inhibitory mechanisms. On the isolated Helix heart the crude ACT 9505 and PCC 6506 extracts evoked frequency increase and transient twitch contraction, opposite to the ACh evoked heart relaxation. Anatoxin-a similarly contracted the heart but did not increase its contration frequency. These data suggest the involvement of some non-cholinergic mechanisms, acting very likely by direct modulation of the electrical or contractile system of the isolated heart. Diversity of the effects evoked by the cyanobacterial extracts in the CNS and heart suggest pharmacologically different neuroactive components among the secondary metabolites of the cyanobacteria acting on both (anatoxin-a like) cholinergic and (unidentified) non-cholinergic receptors. PMID- 22776490 TI - Analysis of DNA endoreplication in the brain neurons in the terrestrial slug, Limax valentianus. AB - DNA endoreplication is the DNA synthesis without cell division, resulting in the generation of a nucleus containing a larger amount of genomic DNA compared to a normal diploid genome. There are many such giant neurons in the molluscan brain that are generated as a result of repeated endoreplication. However, it has been controversial whether the endoreplication is the whole genome replication (polyploidy) or the local amplification of the genes that are necessary for the neuron's function (polyteny/polysomy). Here in this study, we investigated these two possibilities by (1) immunohistochemical analysis of the distribution of 5' bromodeoxyuridine incorporated into the nuclei of the brain neurons, and by (2) quantitative genomic PCR directed to two different genes expressed in specific brain regions. Our data supported the view that the DNA endoreplication is the whole genome replication rather than the local amplification of a specific genomic region. PMID- 22776491 TI - Repetitive noxious stimulus altered the shadow-induced withdrawal behavior in Lymnaea. AB - Stress alters adaptive behaviors including vigilance behaviors. In Lymnaea one of these vigilance behavior is a heightened withdrawal response to a shadow. The shadow withdrawal response (SWR) is mediated by dermal photoreceptors located primarily on the foot, mantle cavity, and skin around the pneumostome area. Here we asked whether we could obtain a neural correlate of the heightened SWR and other essential behaviors following traumatic stress. We measured the electrophysiological properties of 'Right Pedal Dorsal 11 (RPeD11)', the interneuron that plays a major role in mediating the whole-body withdrawal response. In traumatized snails 24 hours after the trauma they responded not only to a shadow stimulus with an augmented withdrawal response, but suppressed in locomotive, feeding and respiratory behavior. Their behavioral change lasted at least one week. Accompanying the behavioral change in these 'traumatized' preparations there are a number of significant changes in the neuronal properties of RPeD11 compared to naive preparations. For example, RPeD11 is significantly more depolarized (~10 mV) has significantly larger input resistance, and the duration of the response elicited by the shadow persists longer. All these changes result in an increased RPeD11 response and seem to raise their defensive alert level. PMID- 22776492 TI - In vitro aversion conditioning in Lymnaea. Short communication. AB - In an in vitro semi-intact Lymnaea preparation we were successful in using a training procedure to bring about Conditioning Taste Aversion (CTA ). Following paired presentation of the CS (sucrose) and US (tactile), the CS no longer elicits feeding. We can use sucrose to the lips in the semi-intact preparation as the CS; while we use direct current injection to depolarize RPeD11 as the US. Following pairing of these stimuli, the CS no longer elicits fictive feeding. We can determine the changes in synaptic input to neurons that play key roles in controlling feeding behavior. PMID- 22776493 TI - Insulin and memory in Lymnaea. AB - The pond snail, Lymnaea stagnalis, is capable of learning conditioned taste aversion (CTA) and consolidating this CTA into long-term memory (LTM). The DNA microarray experiments showed that some of molluscan insulin-related peptides (MIPs) were up-regulated in snails exhibiting CTA-LTM. On the other hand, the electrophysiological experiments showed that application of secretions from the MIPs-containing cells evoked long-term potentiation (LTP) at the synapses between the cerebral giant cell (a key interneuron for CTA) and the B1 motoneuron (a buccal motoneuron). We thus hypothesized that MIPs and MIP receptors play an important role at the synapses, probably underlying the CTA-LTM consolidation process. To examine this hypothesis, we applied the antibody, which recognizes the binding site of mammalian insulin receptors and is thought to cross-react MIP receptors, to the Lymnaea CNS. Our present data showed that an application of the antibody for insulin receptors to the isolated CNS blocked LTP, and that an injection of the antibody into the Lymnaea abdominal cavity inhibited LTM consolidation, but not CTA formation. PMID- 22776494 TI - Origin of automaticity and neural regulation of peristalsis in the gastrointestinal tract of Aplysia and Lymnaea. Short communication. AB - We examined whether the enteric nervous system (ENS) is capable of controlling autonomous peristalsis, which occurs in the crop of Aplysia as well as in the esophagus of Lymnaea. Interestingly, "pacemaker neurons", which lead peristaltic rhythm, were found in the gizzard in Aplysia and in the crop in Lymnaea; both of these structures are located distal to the regions exhibiting peristalsis. Thus, the bursting activity of the ENS first occurred in lower regions and then progressed in an ascending direction (i.e. in the opposite direction of peristalsis). The two species are thought to differ in terms of the mechanisms involved in producing peristalsis. PMID- 22776495 TI - Pharmacological analysis of locomotion and heart contraction during the development of Helisoma (Mollusca: Gastropoda). Short communication. AB - We investigated involvement of different 5-HT receptors in regulation of ciliary rotation, gliding locomotion and heartbeat of Helisoma embryo at pre- and post metamorphic stages. Pharmacological analysis suggested that activation of 5-HT1 receptor enhance ciliary rotation but do not affect gliding locomotion. Activation of 5-HT4 receptor depresses both types of locomotion. Before metamorphosis heart contraction is depressed by activation of 5-HT4 and enhanced by activation of 5-HT7 receptor. However, the heart became insensitive to all agonists by hatching. We hypothesized that alterations in affinity or expression of particular 5-HT receptors can underlie the well-coordinated character of serotonin-dependent larval behavior. PMID- 22776496 TI - Delayed action of serotonin in molluscan development. AB - Serotonin (5-HT) is known to induce a wide range of short-term and long-term (or delayed) effects. In the present paper we demonstrated that short time-window application of the 5-HT precursor 5-hydroxytryptophan during early cleavage stages results in both irreversible morphological malformation (exogastrulation) and distinct changes in behavior of young animals of the freshwater snail, Lymnaea stagnalis (Mollusca: Gastropoda). Pharmacological and immunocytochemical analysis confirmed that both the increase of intracellular 5-HT level within the cleaved blastomers and activation of membrane 5-HT2-like type receptors are required for the appearence of these phenomena. PMID- 22776497 TI - Serotonin transport and synthesis systems during early development of invertebrates: functional analysis on a bivalve model. Short communication. AB - Serotonin (5.HT) is known to be functionally active during early development in both vertebrates and invertebrates. However, the presence of 5-HT and its synthesis and transport system has not yet been demonstrated in bivalve early development. The presence of 5-HT was immunochemically demonstrated at the cleavage stage of bivalve Mytilus trossulus. 5-HT level dramatically increased within all embryonic cells after incubation with 5-HTP but not after incubation with tryptophan and 5-HT. The first 5-HT uptake by specific transporter was detected at 13 hpf blastula stage only and it was restricted to one distinct cell. PMID- 22776498 TI - Innervation of bivalve larval catch muscles by serotonergic and FMRFamidergic neurons. AB - Bivalve larvae use catch muscles for rapid shell closure and maintenance of the closed condition. We used specific antibodies against the muscle proteins together with phalloidin and neuronal markers, FMRFamide and serotonin (5-HT), to analyze mutual distribution of muscle and neuronal elements in larvae of the mussel, Mytilus trossulus, and the oyster, Crassostrea gigas. At trochophore and early veliger stages no anatomical connections between muscular and nervous system were detected. By the pediveliger stage the 5-HT innervation of the anterior adductor developed in oyster only, while rich FMRFa innervation of the adductor muscles developed in both species. Possible roles and mechanisms of FMRFamide and serotonin in the regulation of the catch state are discussed. PMID- 22776499 TI - Modulation of Mytilus trossulus (Bivalvia: Mollusca) larval survival and growth in culture. Short communication. AB - Commercial importance and ability to live in a wide range of salinities have made the common mussel, Mytilus trossulus, a relevant model to study modulation of larval growth and development. We investigated the effects of various salinities combined with neomycin and ampicillin application on Mytilus larvae survival and growth. Both neomycin and ampicillin enhanced trochophore and veliger survival under condition of low salinity. The average veliger size was increasing in accordance with the increase of salinity. In case of neomycin treatment 3.6% of the larvae reached the pediveliger stage. No abnormalities of larval morphology of the FMRFamide and 5-HT systems occurred after 7 days of culturing with both antibiotics. PMID- 22776500 TI - Poikiloderma-like primary cutaneous amyloidosis confined to the calves in a Chinese man. PMID- 22776501 TI - Feasibility of thoracoscopic esophagectomy after neoadjuvant chemotherapy. AB - INTRODUCTION: Minimally invasive esophagectomy has been increasingly accepted to treat esophageal cancer. In Japan, neoadjuvant chemotherapy followed by surgery has become the standard procedure for advanced esophageal cancer. A randomized control study has shown neoadjuvant chemotherapy's survival benefits, but it is unknown whether minimally invasive esophagectomy after chemotherapy is viable. This study investigated the feasibility of thoracoscopic esophagectomy after neoadjuvant chemotherapy. METHODS: From a database of patients with esophageal cancer, 105 patients who had undergone thoracoscopic esophagectomy with radical lymphadenectomy were analyzed retrospectively. Among them, 51 patients had received neoadjuvant chemotherapy with 5-fluorouracil and cisplatin (NAC group). Their operative outcomes, including operative duration, blood loss, the number of dissected lymph nodes, and postoperative morbidity and mortality, were compared with those of 54 patients who underwent surgery without neoadjuvant chemotherapy (control group). The efficacy of neoadjuvant chemotherapy was also assessed. RESULTS: The operating time in the NAC group was significantly longer than in the control group (543 vs 472 min, P < 0.001), but the blood loss was less (323 vs 528 mL, P < 0.001). Recurrent laryngeal nerve palsy was the most frequently observed complication in both groups (27% vs 32%, P = 0.65). No significant differences were observed in the frequency of postoperative complications. There was no mortality in either group. In the NAC group, 43 patients (84.3%) underwent curative resection, and response of more than two-thirds of the pathological tumor was achieved in 11 patients (21.6%), including complete response in one patient (2.0%). CONCLUSION: Thoracoscopic esophagectomy following neoadjuvant chemotherapy could be safely adopted for patients with advanced esophageal cancer. PMID- 22776502 TI - Age effects on survival from early breast cancer in clinical settings in Australia. AB - BACKGROUND: The study aim was to determine whether age is an independent risk factor for survival from early invasive breast cancer in contemporary Australian clinical settings. METHODS: The study included 31 493 breast cancers diagnosed in 1998-2005. Risk of death from breast cancer was compared by age, without and with adjustment for clinical risk factors, using Cox proportional hazard regression. RESULTS: Risk of breast cancer death was elevated for cancers of larger size, higher grade, positive nodal status, oestrogen receptor negative status, vascular invasion and multiple foci. Ductal lesions presented a higher risk than other lesions. Adjusting for these factors, the relative risk of breast cancer death (95% confidence limits) was lower for 40-49-year-olds at 0.80 (0.66, 0.96) than for the reference category under 40 years, but higher for 70-79-year olds at 1.64 (1.36, 1.98) and women aged 80 years or more at 2.19 (1.79, 2.69). The risk for 50-69-year-olds and women under 40 years was similar. Risk-factor adjustment reduced the difference in risk between the reference category under 40 years and 40-49-year-olds, largely eliminated the lower relative risk for 50-69 year-olds, and increased the relative risks for women aged 70-79 years and older. DISCUSSION: Survivals in women under 40 and over 70 years of age are poorer than for 40-69-year-olds. Research is needed into the best treatment modalities for younger women and older women with co-morbidity. PMID- 22776503 TI - Development of a colloidal gold immunochromatographic test strip for detection of lymphocystis disease virus in fish. AB - AIMS: To develop a gold immunochromatographic test strip for on-site rapid detection of lymphocystis disease virus (LCDV). METHODS AND RESULTS: Monodispersional colloidal gold and gold-labelled anti-LCDV monoclonal antibody (McAb) 2D11 were prepared and characterized by UV-visible spectroscopy and transmission electron microscopy. Gold-labelled probe was used as the detection antibody, and goat anti-mouse IgG at the control line and anti-LCDV McAb 1A8 at the test line of the test strip served as the capture antibody. The positive results could be easily judged by the presence of a red test line with naked eye within 10 min. The test strip, in good agreement with enzyme-linked immunosorbent assay and dot-blotting in sensitivity and LCDV detection, gave a detection limit of 1 MUg ml(-1) of LCDV and was stable for 6 months at room temperature and 12 months at 4 degrees C. CONCLUSIONS: The test strip was specific, simple and convenient for rapid detection of LCDV presenting good stability and reproducibility. SIGNIFICANCE AND IMPACT OF THE STUDY: This ready-to-use test strip allows on-site rapid detection of LCDV in fish without the requirement of specialized equipments and professional personnel, which could augment the practical application for diagnosis of LCDV even in disadvantage areas. PMID- 22776504 TI - Hypotheses on the stability and variation of human sex ratios at birth. AB - Human sex ratios at birth simultaneously show both significant variation with a number of variables, and striking stability across time. Hypotheses on these features are discussed here. A) The causes of the stability are not established. B) There are several hypotheses which purport to explain sex ratio variation. 1. The Trivers-Willard hypothesis has had only limited success. This may be because (from a methodological standpoint) it has an unusual provenance in that it is not a response to a perceived need for explanation of an observed phenomenon. At present there seems too much evidence in its favour for this hypothesis to be rejected, and too much against it, for it to be accepted. 2. My hypothesis proposes that hormone concentrations (of both parents) around the time of conception partially control the sex of the zygote. A substantial quantity of data has been adduced in favour of this hypothesis. But it cannot explain all types of variation of sex ratios at birth. 3. It has been proposed by Catalano that other variation in sex ratios at birth is associated with maternal stress during pregnancy. He and his co-workers have adduced substantial quantities of data to support this hypothesis too. PMID- 22776505 TI - Optimization of the visco-elastic parameters describing the heel-region of a prosthesis. AB - Although compliance (visco-elasticity) of a prosthesis has the potential to affect clinically relevant aspects of a lower extremity amputee's gait, it is currently unknown what the compliant parameter values should be. Here, a simple dynamical model is used to approximate walking with a compliant prosthesis. An exhaustive search is used to identify the optimal compliant element parameter set in terms of the model's stability as measured by the reciprocal of the gait sensitivity norm (rGSN). We identified a parameter set yielding a 17% larger rGSN than the best commercially available prosthesis; however, this is unlikely to be the global optimum for the physically realizable visco-elastic parameter space. Due to the nonlinear effects of the compliant elements, it is difficult to make generalizations about speed and step length, such difficulties are not present with simpler contact models. However, there is some evidence to support a possible trade-off between efficiency and stability. PMID- 22776506 TI - Anthelmintic metabolism in parasitic helminths: proteomic insights. AB - Anthelmintics are the cornerstone of parasitic helminth control. Surprisingly, understanding of the biochemical pathways used by parasitic helminths to detoxify anthelmintics is fragmented, despite the increasing global threat of anthelmintic resistance within the ruminant and equine industries. Reductionist biochemistry has likely over-estimated the enzymatic role of glutathione transferases in anthelmintic metabolism and neglected the potential role of the cytochrome P-450 superfamily (CYPs). Proteomic technologies offers the opportunity to support genomics, reverse genetics and pharmacokinetics, and provide an integrated insight into both the cellular mechanisms underpinning response to anthelmintics and also the identification of biomarker panels for monitoring the development of anthelmintic resistance. To date, there have been limited attempts to include proteomics in anthelmintic metabolism studies. Optimisations of membrane, post translational modification and interaction proteomic technologies in helminths are needed to especially study Phase I CYPs and Phase III ABC transporter pumps for anthelmintics and their metabolites. PMID- 22776507 TI - Nicotine improves performance in an attentional set shifting task in rats. AB - A large number of studies in both humans and experimental animals have demonstrated nicotine-induced improvements in various aspects of cognitive function, including attention and memory. The prefrontal cortex (PFC) is thought to be critically involved in the modulation of executive function and these attentional processes are enhanced by nicotine acting at nicotinic acetylcholine receptors. The involvement of nicotinic processes on cognitive flexibility in particular has not been specifically investigated. The effects of nicotine on attentional flexibility were therefore evaluated using the rodent attentional set shifting task in rats. Nicotine injected both acutely and following repeated pre exposure significantly improved both intradimensional and extradimensional set shifting performance in the task. Further investigation of the acute effects of nicotine demonstrated this improvement in attentional flexibility to be dose dependent. These results implicate the nicotinic receptor system in the mediation of processes underlying cognitive flexibility and suggest that nicotine improves attentional flexibility in rats, both within and between perceptual dimensions of a compound stimulus. Nicotine-induced alterations in prefrontal circuitry may underlie these effects on cognitive flexibility. This article is part of a Special Issue entitled 'Cognitive Enhancers'. PMID- 22776509 TI - High-frequency mini-probe ultrasound as a useful adjunct in the management of patients with malignant colorectal polyps. AB - AIM: Colorectal polyps with a focus of malignancy, identified postpolypectomy, pose a management challenge of whether endoscopic treatment is adequate or whether further surgical resection is required. This study assessed 12- and 20 MHz colonoscopic ultrasound to evaluate the presence of residual disease and local lymph nodes. METHOD: Consecutive cases of all colorectal polyps with a focus of malignancy were included. Colonoscopic high-frequency ultrasound was performed (20-MHz mini-probes for residual polyps and 12-MHz ultrasound for local lymph nodes) in the region of previous polypectomy. Biopsies were taken of the polypectomy site if any abnormalities were seen. RESULTS: Twenty-one malignant polyps (sigmoid, n = 10; rectum, n = 8; transverse colon, n = 1; ascending colon, n = 1; and caecum, n = 1) were identified. All were invasive adenocarcinomas; 12 were intramucosal and nine were submucosal (seven sm1 lesions in the upper third of the submucosa; and two sm2 lesions in the middle third of the submucosa). Excision was histologically complete in 12 patients, four had involved margins and histology was uncertain in five owing to diathermy artefacts. Further colonoscopy revealed a residual abnormality in eight patients. The 12- and 20-MHz ultrasound imaging revealed mucosal irregularity with normal bowel-wall layers and no lymph-node involvement, with normal histology. High-frequency ultrasound was normal in the remaining 13 patients. At the time of writing, 15 (72%) of the 21 patients were disease free without further surgery. Six of the 21 patients underwent surgery, despite normal high-frequency ultrasound findings, because of submucosal invasion (sm1 or sm2) and uncertain completeness of resection. The specimens were free of cancer in all six patients. CONCLUSION: High-frequency ultrasound is feasible for the assessment of colorectal malignant polyps. PMID- 22776508 TI - Genome-wide analysis of the MYB transcription factor superfamily in soybean. AB - BACKGROUND: The MYB superfamily constitutes one of the most abundant groups of transcription factors described in plants. Nevertheless, their functions appear to be highly diverse and remain rather unclear. To date, no genome-wide characterization of this gene family has been conducted in a legume species. Here we report the first genome-wide analysis of the whole MYB superfamily in a legume species, soybean (Glycine max), including the gene structures, phylogeny, chromosome locations, conserved motifs, and expression patterns, as well as a comparative genomic analysis with Arabidopsis. RESULTS: A total of 244 R2R3-MYB genes were identified and further classified into 48 subfamilies based on a phylogenetic comparative analysis with their putative orthologs, showed both gene loss and duplication events. The phylogenetic analysis showed that most characterized MYB genes with similar functions are clustered in the same subfamily, together with the identification of orthologs by synteny analysis, functional conservation among subgroups of MYB genes was strongly indicated. The phylogenetic relationships of each subgroup of MYB genes were well supported by the highly conserved intron/exon structures and motifs outside the MYB domain. Synonymous nucleotide substitution (dN/dS) analysis showed that the soybean MYB DNA-binding domain is under strong negative selection. The chromosome distribution pattern strongly indicated that genome-wide segmental and tandem duplication contribute to the expansion of soybean MYB genes. In addition, we found that ~ 4% of soybean R2R3-MYB genes had undergone alternative splicing events, producing a variety of transcripts from a single gene, which illustrated the extremely high complexity of transcriptome regulation. Comparative expression profile analysis of R2R3-MYB genes in soybean and Arabidopsis revealed that MYB genes play conserved and various roles in plants, which is indicative of a divergence in function. CONCLUSIONS: In this study we identified the largest MYB gene family in plants known to date. Our findings indicate that members of this large gene family may be involved in different plant biological processes, some of which may be potentially involved in legume-specific nodulation. Our comparative genomics analysis provides a solid foundation for future functional dissection of this family gene. PMID- 22776511 TI - Experimental infection with equid herpesvirus 3 in seronegative and seropositive mares. AB - Equine coital exanthema (ECE), caused by equid herpesvirus 3 (EHV-3), has been recognized as an economically significant venereal disease for years. However, no infection models on the natural host have been established. In order to set up an experimental infection protocol, seronegative and seropositive mares were topically inoculated in the perineal region with 4 * 10(6)TCID(50)/ml of EHV-3. Clinical signs were then evaluated by means of a designed scoring system, and body temperature was recorded daily. Virological, and serological studies were also performed. Typical ECE lesions, with clinical scores of 90, 92, 160 and 172, were observed in the four seronegative animals. Only mild ECE lesions were observed in the two seropositive mares, being the clinical scores 53 and 41. Both groups of mares shed the virus, but the duration of virus shedding was shorter and its intensity was lower in seropositive mares than in seronegative ones. Moreover, EHV-3 antibody response was detected in both seronegative and seropositive mares after experimental infection and re-infection, being more moderate in seropositive ones. As a conclusion, EHV-3 infection of mares was experimentally achieved in a reproducible manner. The typical lesions of ECE were observed after topical EHV-3 infection in seronegative mares, in association with virus excretion and neutralizing antibody kinetics. PMID- 22776510 TI - Correlation between the functional impairment of bone marrow-derived circulating progenitor cells and the extend of coronary artery disease. AB - BACKGROUND: Bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with coronary heart disease are impaired with respect to number and functional activity. However, the relation between the functional activity of BM CPCs and the number of diseased coronary arteries is yet not known. We analyzed the influence of the number of diseased coronary arteries on the functional activity of BM-CPCs in peripheral blood (PB) in patients with ischemic heart disease (IHD). METHODS: The functional activity of BM-CPCs was measured by migration assay and colony forming unit in 120 patients with coronary 1 vessel (IHD1, n = 40), coronary 2 vessel (IHD2, n = 40), coronary 3 vessel disease (IHD3, n = 40) and in a control group of healthy subjects (n = 40). There was no significant difference of the total number of cardiovascular risk factors between IHD groups, beside diabetes mellitus (DM), which was significantly higher in IHD3 group compared to IHD2 and IHD1. RESULTS: The colony-forming capacity (CFU-E: p < 0.001, CFU-GM: p < 0.001) and migratory response to stromal cell-derived factor 1 (SDF-1: p < 0.001) as well as vascular endothelial growth factor (VEGF: p < 0001) of BM-CPCs were reduced in the group of patients with IHD compared to control group. The functional activity of BM-CPCs was significantly impaired in patients with IHD3 as compared to IHD1 (VEGF: p < 0.01, SDF-1: p < 0.001; CFU-E: p < 0.001, CFU-GM: p < 0.001) and to IHD2 (VEGF: p = 0.003, SDF-1: p = 0.003; CFU-E: p = 0.001, CFU-GM: p = 0.001). No significant differences were observed in functional activity of BM-CPCs between patients with IHD2 and IHD1 (VEGF: p = 0.8, SDF-1: p = 0.9; CFU-E: p = 0.1, CFU-GM: p = 0.1). Interestingly, the levels of haemoglobin AIc (HbAIc) correlated inversely with the functional activity of BM-CPCs (VEGF: p < 0.001, r = -0.8 SDF-1: p < 0.001, r = -0.8; CFU-E: p = 0.001, r = -0.7, CFU-GM: p = 0.001, r = -0.6) in IHD patients with DM. CONCLUSIONS: The functional activity of BM-CPCs in PB is impaired in patients with IHD. This impairment increases with the number of diseased coronary arteries. Moreover, the regenerative capacity of BM-CPCs in ischemic tissue further declines in IHD patients with DM. Furthermore, monitoring the level of BM-CPCs in PB may provide new insights in patients with IHD. PMID- 22776512 TI - Expression patterns of five polymorphic membrane proteins during the Chlamydia abortus developmental cycle. AB - It has been suggested that polymorphic membrane proteins (Pmps) belonging to the Type V autotransporter protein family play an important role in the pathogenesis of Chlamydia abortus (C. abortus; formerly Chlamydophila abortus) infection. In a previous study we demonstrated the expression of all the pmps at the transcriptional level. The purpose of this study was to measure the number of Pmp positive inclusions throughout the C. abortus developmental cycle to investigate heterogeneity in expression patterns. McCoy cells were infected with C. abortus and analysed for Pmp expression over a 72 h period by fluorescent immunocytochemistry. Pmp18D could be detected at all analysed time points, and could only be accurately quantified from 36 hpi while Pmp10G positive inclusions could be visualised from 36hpi. Expression of Pmps 13G, 16G and 17G could only be visualised later in the cycle and within less than half of visualised inclusions. These results indicate that while expression of specific Pmps is constitutive (Pmp18D), the pattern of expression of other Pmps is more variable. This suggests that different members of the Pmp family may play different roles within the developmental cycle of the organism, with some (Pmps10G and 18D) having roles throughout the cycle, while the heterogeneity of expression of others may aid in antigenic variation. PMID- 22776513 TI - Seroprevalence and risk factors associated to West Nile virus in horses from Andalusia, Southern Spain. AB - West Nile virus (WNV) is recognized as an emerging zoonotic pathogen, whose incidence in horses, humans and birds has increased significantly in different European countries in the last decade. A serosurvey study was carried out in non vaccinated horses to determine the geographical distribution of WNV in Andalusia (Southern Spain), and to assess the factors that influence the risk of WNV infection in horses. Antibodies to WNV were detected in 54 out of 510 horses analyzed by a blocking ELISA, of which 36 were confirmed by micro virus neutralization test (7.1%; CI(95%): 4.9-9.3). A total of 28 out of the 348 equine herds (8.3%; CI(95%): 5.4-11.2) had at least one seropositive animal. A generalized estimating equations model showed that the main risk factors associated to WNV seroprevalence were: number of horses within the holding (low), transport of the horse within the last six months (Yes) and presence of mosquitoes in the holding (Yes). The results demonstrated that WNV circulation in Andalusia was more widespread than previously reported. Besides, the distribution of WNV infections was not homogeneous as significant differences among provinces were observed. The results show the need to improve the active surveillance in Spain, so that the early detection of WNV circulation allows the establishment control measures such as vaccination and implementation of vector control programs during the risk period. PMID- 22776514 TI - An experimental Helicobacter suis infection causes gastritis and reduced daily weight gain in pigs. AB - Helicobacter suis is a zoonotically important bacterium, that has been associated with gastritis and ulcerative lesions of the pars oesophagea of the stomach in pigs. Its exact role in these pathologies, however, still remains controversial. Therefore, a total of 29 medicated early weaned piglets were inoculated intragastrically or orally, with a total of 2 * 10(9) viable H. suis bacteria and the effect on gastric pathology and weight gain was determined. Twenty-three medicated early weaned piglets were inoculated with a sterile culture medium and used as sham-inoculated controls. The animals were euthanized between 28 and 42 days after inoculation. Infected animals showed a more severe gastritis compared to the control group. There was also a significant reduction of approximately 60 g per day (10%) in weight gain in H. suis inoculated animals compared to the sham inoculated control animals. In conclusion, this study demonstrates for the first time that a pure in vitro culture of H. suis not only causes gastritis but also a marked decrease of the daily weight gain in experimentally infected pigs. PMID- 22776515 TI - Comparison of computed tomography and autopsy in detection of injuries after unsuccessful cardiopulmonary resuscitation. AB - AIM: Computed tomography (CT) has been suggested as an aid or even a replacement for autopsy. The aim of this trial was to study the conformity of the two methods in finding injuries in non-surviving patients after unsuccessful cardiopulmonary resuscitation. METHODS: In this prospective study, 31 patients were submitted to a CT prior to autopsy after unsuccessful resuscitation attempts. Pathological findings were noted by both the radiologist and the pathologists in a specified protocol. The pathologists and radiologist were blinded from each other's results. RESULTS: CT and autopsy revealed rib fractures in 22 and 24 patients respectively (kappa=0.83). In 8 patients, CT revealed more rib fractures than autopsy; and in 12 patients, autopsy revealed more rib fractures than CT. In 7 patients, neither method showed any rib fractures. The mean difference between the two methods in detecting rib fractures was 0.16 (S.D.: +/- 3.174, limits of agreement: -6.19 to 6.51). The kappa value for sternal fractures was 0.49. A total of 260 pathological findings were noted by CT and 244 by autopsy. The average patient showed a median of 9 injuries (every fracture counted as one injury), independent of the method used in detecting the injuries. CONCLUSIONS: There was a strong concordance between the two methods in finding rib fractures but not sternal fractures and these results support the concept of CT as a valuable complement to autopsy in detecting rib fractures after unsuccessful cardiopulmonary resuscitation but not as a replacement. Other injuries did not show the same concordance. PMID- 22776517 TI - Transportability of tertiary qualifications and CPD: a continuing challenge for the global health workforce. AB - BACKGROUND: In workforces that are traditionally mobile and have long lead times for new supply, such as health, effective global indicators of tertiary education are increasingly essential. Difficulties with transportability of qualifications and cross-accreditation are now recognised as key barriers to meeting the rapidly shifting international demands for health care providers. The plethora of mixed education and service arrangements poses challenges for employers and regulators, let alone patients; in determining equivalence of training and competency between individuals, institutions and geographical locations. DISCUSSION: This paper outlines the shortfall of the current indicators in assisting the process of global certification and competency recognition in the health care workforce. Using Organisation for Economic Cooperation and Development (OECD) data we highlight how International standardisation in the tertiary education sector is problematic for the global health workforce. Through a series of case studies, we then describe a model which enables institutions to compare themselves internally and with others internationally using bespoke or prioritised parameters rather than standards. SUMMARY: The mobility of the global health workforce means that transportability of qualifications is an increasing area of concern. Valid qualifications based on workplace learning and assessment requires at least some variables to be benchmarked in order to judge performance. PMID- 22776516 TI - Medical emergency team response for the non-hospitalized patient. AB - OBJECTIVES: Rapid response systems (RRS) evolved to care for deteriorating hospitalized patients outside of the ICU. However, emergent critical care needs occur suddenly and unexpectedly throughout the hospital campus, including areas with non-hospitalized persons. The efficacy of RRS in this population has not yet been described or tested. We hypothesize that non-hospitalized patients accrue minimal benefit from ICU physician participation in the RRS. DESIGN: A retrospective review of all RRS events in non-hospitalized patients for a 28 month period was performed in a large, urban university medical center. Location, patient type and age, activation trigger, interventions performed, duration of event and disposition were recorded. Admission diagnosis and length of stay were also recorded for patients admitted to the hospital. SETTING: Academic medical center. PATIENTS: Non-hospitalized persons requiring evaluation by the medical emergency team. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were a total of 1778 RRS activations during the study period. 232 (13%) of activations were for non-hospitalized patients. The patient cohort consisted of outpatients, visitors, and staff. Triggers for RRS activation were neurologic change (42%), cardiac (27%), respiratory (16%), and staff concerns (16%). The mean duration of the response was 38 min. The most common interventions performed included administration of oxygen (46%), intravenous fluids (13%) and dextrose (6%). 82% of patients were taken to the emergency department and 32% of the ED cohort were admitted to the hospital. CONCLUSIONS: Perceived emergencies in non-hospitalized patients occur commonly but require minimal emergent intervention. Restriction of critical care physician involvement to inpatient deteriorations should be considered when designing a RRS. Future studies are needed to evaluate the utility of non-physician provider led rapid response teams with protocol-driven interventions for similar populations. PMID- 22776518 TI - Early oral intake after reconstruction with a free flap for cancer of the oral cavity. AB - To allow healing of the surgical wound patients are traditionally given nothing by mouth for 6-12 days after resection and reconstruction of a cancer of the oral cavity. Our aim was to assess the impact of introducing oral intake within 6 days postoperatively. Consecutive patients who had resection and reconstruction of a cancer of the oral cavity with a free flap within an 8-year period were selected from the head and neck database. Personal and social data; type, stage, and site of the tumour; type of resection and free flap; postoperative complications; and duration of hospital stay were recorded, supplemented by review of casenotes for the time that oral intake was started, duration of nasogastric and tracheostomy intubation, and changes in body weight. Patients in the early oral intake group started oral intake within 5 days postoperatively, and those in the late group began feeding from postoperative day 6. The duration of hospital stay in the early group was significantly shorter than that in the late group. There was, however, no difference in the morbidity, including orocutaneous fistula, between the two groups. The duration of nasogastric and tracheostomy intubation was shorter, and weight loss was less, in the early group than in the late group, but not significantly so. Early oral feeding does not increase the morbidity for patients having resection and reconstruction with free flaps for cancers of the oral cavity. Early oral intake is associated with a shorter hospital stay, and this may have implications for improved postoperative outcome. PMID- 22776519 TI - Influence of various treatments including povidone-iodine and healing stimulatory reagents in a rabbit ear wound model. AB - Selecting an appropriate treatment for a given case of skin wound is crucial for inducing optimal healing. We used an animal model developed from normal rabbit ears in order to assess the efficacy of treatments for skin wounds with or without a wet dressing, anti microbial reagent or topical wound-stimulatory reagents. The degree of healing in each group was evaluated and compared using four histological parameters: (i) degree of reepithelialisation, (ii) amount of granulation tissue formation, and (iii) the number of capillary lumens and (iv) fibroblasts in the granulation tissue. Treatment using wet dressings resulted in an increase in capillary number compared with the open dry wound. Although the retention of povidone-iodine (PI) in wound tissue after application significantly inhibited reepithelialisation (P < 0.05), rinsing PI off with saline was comparable in effect to using only a wet dressing. The three topical reagents, namely, basic fibroblast growth factor, prostaglandin E1 and dibutyryl cyclic adenosine monophosphate, significantly improved reepithelialisation (P < 0.05). In conclusion, wounds should be kept hydrated by applying topical reagents. If there are any signs of bacterial infection, PI can be applied and rinsed later with saline in order to minimise its cytotoxic effects. PMID- 22776520 TI - Vector capacity of Anopheles sinensis in malaria outbreak areas of central China. AB - BACKGROUND: Both falciparum and vivax malaria were historically prevalent in China with high incidence. With the control efforts, the annual incidence in the whole country has reduced to 0.0001% except in some areas in the southern borders after 2000. Despite this, the re-emergence or outbreak of malaria was unavoidable in central China during 2005-2007. In order to understand the role of the vector in the transmission of malaria during the outbreak period, the vector capacity of An. sinensis in Huanghuai valley of central China was investigated. FINDINGS: The study was undertaken in two sites, namely Huaiyuan county of Anhui province and Yongcheng county of Henan province. In each county, malaria cases were recorded for recent years, and transmission risk factors for each study village including anti-mosquito facilities and total number of livestock were recorded by visiting each household in the study sites. The specimens of mosquitoes were collected in two villages, and population density and species in each study site were recorded after the identification of different species, and the blood-fed mosquitoes were tested by ring precipitation test. Finally, various indicators were calculated to estimate vector capacity or dynamics, including mosquito biting rate (MBR), human blood index (HBI), and the parous rates (M). Finally, the vector capacity, as an important indicator of malaria transmission to predict the potential recurrence of malaria, was estimated and compared in each study site.About 93.0% of 80 households in Huaiyuan and 89.3% of 192 households in Yongcheng had anti-mosquito facilities. No cattle or pigs were found, only less than 10 sheep were found in each study village. A total of 94 and 107 Anopheles spp. mosquitos were captured in two study sites, respectively, and all of An. sinensis were morphologically identified. It was found that mosquito blood-feeding peak was between 9:00 pm and 12:00 pm. Man biting rate of An. sinensis was 6.0957 and 5.8621 (mosquitoes/people/night) estimated by using half-night human bait trap method and full-capture method, respectively. Human blood indexes (HBI) were 0.6667 (6/9) and 0.6429 (18/28), and man-biting habits were 0.2667 and 0.2572 in two sites, respectively. Therefore, the expectation of infective life and vector capacity of An. sinensis was 0.3649-0.4761 and 0.5502-0.7740, respectively, in Huanhuai valley of central China where the outbreak occurred, which is much higher than that in the previous years without malaria outbreak. CONCLUSIONS: This study suggests that vivax malaria outbreak in Huanhuai valley is highly related to the enhancement in vector capacity of An. sinensis for P. vivax, which is attributed to the local residents' habits and the remarkable drop in the number of large livestock leading to disappearance of traditional biological barriers. PMID- 22776521 TI - [Changing trends in obstetrics in the last decade]. AB - The author (who has four decades of clinical and managerial practice) analyses the changing trends in obstetrics that occurred in the last decade. He focuses on the main points where the most significant professional developments have happened (prenatal care, new professional guidelines, and integrated services). This work covers the principles of prevention and the advanced diagnostics in the field of prenatal and obstetrical care. Finally, the author describes the need for structural and functional reorganization in obstetrics. PMID- 22776522 TI - [An overview on envenomings inflicted by the Common adder (Vipera berus) and their treatment in Hungary. Facts and beliefs -- part I]. AB - Consequences of bites by the Common adder (Vipera berus) were reviewed in this study. Patients bitten by snakes from different populations may develop variable symptoms due to geographical venom variation. The correct diagnosis of snake bites and the knowledge of the distribution of venomous snake taxa have a crucial impact on snake bite therapy. The characteristic symptoms of patients bitten by V. berus in Hungary are highlighted. The habitat characteristics, seasonal activity and the Hungarian distribution of the adder are described based on literature data, museum specimens and field observations. However, envenomings are uncommon in Hungary, the annual 3 to 4 incidents have to be taken seriously, regardless of the age and actual health condition of the patients. Contrary to beliefs persisting both among laymen and professionals, the venom of V. berus is powerful. Medical observation of the patients is necessary in the first 5 to 6 hours. Any systemic symptom or progression of the edema requires hospital admission. PMID- 22776523 TI - [Hungarian Diet and Nutritional Status Survey -- the OTAP2009 study. III. Vitamin intake of the Hungarian population]. AB - For the healthy status the adequate intake of vitamins is essential. AIM AND METHOD: The Hungarian Diet and Nutritional Status Survey - joining to the European Health Interview Survey - studied the dietary habits of the Hungarian population. This work presents the vitamins intake. RESULTS: The intake of all water soluble vitamins, vitamin E and D were significantly higher in men than in women. Favourable phenomena were the increased beta-carotene and vitamin C intakes in men and women compared to the earlier data. Intakes of vitamin C, B1-, B2-, B6- and B12, and niacin meet the recommendations. Crucially low intakes of vitamin D and folate were calculated in both genders, particularly in the elders, mainly in case of vitamin D. Imperfect intakes of panthotenic acid and biotin were also observed. CONCLUSIONS: For maintaining the adequate vitamin supply and for prevention of vitamin deficiency, diversified nutrition, information of the population on the basic principles of healthy nutrition and availability of healthy food are essential. PMID- 22776524 TI - [The beginnings of learning about traditional Chinese medicine in Hungary in the 18-19th centuries]. PMID- 22776526 TI - Introduction to Journal of Nursing and Human Sciences. PMID- 22776527 TI - The Asian Research & Collaboration Center for Nursing & Cultural Studies in Japan. AB - The purpose of this paper is to describe current cultural issues in Japanese health-care services that have resulted from the increased immigration. Also described is the establishment of a new academic research centre that will focus on culturally appropriate nursing care. There are many health-care issues in Japan caused by a shortage of health-care workers and disparities in access to health care. The major issues are an increase in the number of foreign patients, foreign nurses and care workers. Despite the occurrence of similar issues in other countries, Japan's situation and the causes are different. In response to dynamic demographic and health-care changes in Japan, we launched the Asian Research & Collaboration Center for Nursing & Cultural Studies at Chiba University Graduate School of Nursing. PMID- 22776528 TI - Factors influencing Thai parent-child interaction in a rapidly changing industrial environment. AB - This paper explores factors influencing parent-child interaction of parents with children age 13-36 months old and working in the industrial setting in the eastern region of Thailand. An ethnographic study was conducted with 22 families. Data were collected through in-depth interviews, participant observation, audiotape/videotape recording and field notes from October 2008 to September 2009. The data were analyzed by means of (i) quantitative data using frequency and percentage and (ii) qualitative data using Roper and Shapira's strategies of content analysis. The factors influencing parent-child interaction include the parental knowledge about child development, their intention and time availability. Other influences noted were economic burdens and support from parents, the factory and the community. These findings provide a greater understanding of the factors influencing parent-child interaction among Thai families with young children. Also, the findings may be useful in the development of effective interventions and/or guidelines that improve the quality of parent child interaction. PMID- 22776529 TI - Comparing child-care values in Japan and China among parents with infants. AB - The purpose of this project was to identify parental child-care values in Japan and China. Participants were 667 parents (432 Japanese and 235 Chinese) of newborn babies. A questionnaire, the Child-care Value Scale, was used to collect the data. Japanese parents' mean scores were significantly higher (indicating more agreement) for parental responsibilities listed in the subscale 'Views about parental role' than those for Chinese parents. The mean scores for 'Negative impressions of child-care' and 'Need for support from others in the parents' environment' subscales for Japanese fathers were significantly lower than for Chinese fathers. Japanese parents believed that mothers were responsible for taking care of their children. This was an obstacle to getting support from people outside the family. Chinese couples believed that parents should share housekeeping and child-care, and obtained public and private support from their community. Findings suggest that parents of infants need community and health care support. PMID- 22776530 TI - Cross-cultural research: challenge and competence. AB - Increasing globalization, population diversity and health disparities among non dominant cultures necessitate cross-cultural research. Research with other cultures is fraught with challenges that must be addressed by the competent cross cultural researcher. Areas for consideration include choice of research foci, ethical concerns, cultural adaptation of research measurements and interventions, participant recruitment and retention, strategies for data collection and analysis, dissemination of findings and perspectives of time. Approaches to dealing with these challenges are addressed, with an emphasis on community-based participatory research. PMID- 22776531 TI - Effects of familiar voices on brain activity. AB - This study aimed to examine the extent to which a familiar voice influences brain activity. Participants were nine healthy female volunteers aged 21-34 years old (with a mean age of 25.78 +/- 4.04 years). Brain activity was recorded during periods of silence, familiar and unfamiliar voices. Electroencephalographic data were collected and analyzed using a frequency rate set at 5 min. To account for emotional influences imbedded into the contents of the voice stimuli, both the voice of a familiar family member and the voice of a stranger were used to record a well-known Japanese fairy tale, 'Momotaro'. Results revealed that listening to familiar voices increased the rate of the beta band (13-30 Hz) in all four brain areas (F3, F4, C3 and C4). In particular, increased activity was observed at F4 and C4. Findings revealed that in study, participants' familiar voices activated cerebral functioning more than unfamiliar voices. PMID- 22776532 TI - Evaluation of the training course for a nursing intervention programme to promote maternal role attainment in pregnant Japanese women who have undergone assisted reproductive technology. AB - This study evaluated the effectiveness of a 2 day training course for a nursing intervention programme to promote maternal role attainment in pregnant Japanese women who have undergone assisted reproductive technology. Participants were 12 Japanese nurses with more than 3 years of clinical experience at reproductive institutions. The effectiveness of the training course was evaluated by assessing the following: (i) understanding of the nursing intervention programme; (ii) attitudes of nurses towards women who are pregnant following assisted reproductive technology; and (iii) self-efficacy for implementing the programme. The training course was effective in increasing basic understanding of the programme and in assisting self-evaluation of the attitudes of participants towards pregnant women. However, acquisition of effective interview skills and changes to make the programme clinically feasible are still needed. Findings suggest that researchers who use this training programme may need to evaluate and include training of nurses in interview skills suitable for their working environments. PMID- 22776533 TI - Promoting cultural awareness in nursing education through international videoconferences. AB - This paper describes a highly successful, 10 year long international videoconference exchange between nursing students in Iwate Prefectural University in northern Japan and the University of North Carolina Wilmington in the United States. A summary of the literature on the use of videoconferencing in nursing education is presented, as well as a brief overview of the collaborative partnership that led to the development of the annual videoconference series. A description of the process for conducting the annual real-time sessions is included along with student perspectives about their experiences. Planning, support and open-mindedness on the part of both students and nursing faculty have contributed to the success of this collaborative effort. PMID- 22776535 TI - Fractional photothermolysis for the treatment of facial wrinkles - searching for optimal treatment parameters in a randomized study in the split-face design. AB - BACKGROUND: Fractionated photothermolysis (FP) is used for the treatment of facial wrinkles. OBJECTIVES: Investigation of effects of different FP treatment parameters in the treatment of facial wrinkles. PATIENTS AND METHODS: In a randomized split-face controlled study 11 patients received 3 FP sessions in 4 week intervals. Keeping the total energy input for each facial side constant, one side was treated with 6 mJ/MTZ with relatively high MTZ density (up to 2,625 MTZ/cm(2) ) and the contralateral side with 70 mJ/MTZ with lower MTZ density (up to 230 MTZ/cm(2) ). Follow-up (FU) visits were performed 1, 3, and 6 months after the last treatment. The cosmetic evaluation was done by the patient self assessments and by assessment of standardized photographs by 3 independent, blinded investigators. Post-treatment side effects were documented daily in a patient diary up to 7 days after the procedure. RESULTS: After 6 months, the patient self-assessments indicated significant improvements (p < 0.005) in wrinkle severity from 5.2 +/- 1.5 to 3.8 +/- 1.3 and 3.7 +/- 1.3 for 6 and 70 mJ/MTZ, respectively, but without significant difference between the energy levels. In contrast, the photographic evaluation by the blinded investigators showed that wrinkle severity was rated significantly better at the sites treated with 70 mJ/MTZ than at the sites treated with 6 mJ/MTZ (p < 0.01). Treatment with 70 mJ/MTZ was significantly more painful than treatment with 6 mJ/MTZ. The typical local reactions to FP, erythema and edema, were also significantly more intense after 70 mJ/MTZ and lasted longer. CONCLUSIONS: FP with higher energy per MTZ at constant total energy input is more effective in the treatment of facial wrinkles than lower energy. The gain in effectiveness is, nonetheless, accompanied by an increase in adverse reactions. The treating physician may use this information to adjust treatment to the preferences of the individual patient. PMID- 22776541 TI - Single-fulcrum laparoscopic cholecystectomy: a single-incision and multi-port technique. AB - BACKGROUND: Single-incision laparoscopic cholecystectomy (LC) is still technically demanding and usually requires specially designed instruments. This article describes our own technique, a single-fulcrum LC using only standard ports and instruments. METHODS: Between March 2009 and December 2010, 130 consecutive patients, all scheduled to undergo elective LC, underwent this single fulcrum LC for benign gallbladder disease. Perioperative surgical outcomes were retrospectively evaluated. RESULTS: One hundred and ten patients (84.6%) underwent successful single-fulcrum LC, and 20 patients (15.4%) were converted to conventional surgery (n= 18) or required additional trocars (n= 2) during the procedure because of umbilical hernia (n= 3), severe inflammation or adhesion (n= 9), impacted cystic duct stone (n= 3), anatomical anomaly (n= 3) and iatrogenic injury (n= 2). Two intraoperative complications (iatrogenic injury) were securely managed using additional trocars and there was no post-operative morbidity or mortality. This single-fulcrum LC could be performed with comparable cost to conventional LC, and the sequential operative time showed reasonable learning curve. CONCLUSION: Single-fulcrum LC is feasible, safe and quite reproducible. The surgical wound can be dramatically reduced at a similar cost to conventional LC. It may be an alternative procedure for most uncomplicated benign gallbladder disease. PMID- 22776542 TI - Successful use of canakinumab in a patient with resistant Behcet's disease. PMID- 22776543 TI - A comparative study of single-incision versus conventional multiport laparoscopic ileocecal resection for Crohn's disease with strictures. AB - INTRODUCTION: Single-incision laparoscopic surgery (SILS) offers excellent cosmetic results compared with conventional multiport laparoscopic surgery. Recently, this technique has been applied to colorectal disease. However, there have been few reports about its application to Crohn's disease (CD) in the literature. The aim of this study is to describe our early experience with SILS for 11 patients with CD and make comparisons with the conventional multiport laparoscopic surgery. METHODS: We reviewed all patients with CD who underwent laparoscopic surgery for the presence of ileocolic strictures at our institution between January 2006 and March 2011. Data from consecutive patients undergoing SILS were analyzed and compared with those from conventional multiport laparoscopic surgeries. RESULTS: During the study period, 11 patients underwent SILS. All surgeries were completed with SILS. Operative time, blood loss and conversions were not significantly different between the two groups. Postoperative complications and length of hospital stay also had no significant difference. CONCLUSION: In conclusion, SILS for CD may be safe and feasible in selected patients, and have better cosmetic results than conventional multiport laparoscopic surgery. Further studies are needed to evaluate the outcome of SILS compared to that of conventional laparoscopic surgery. PMID- 22776534 TI - Predictors of remission in depression to individual and combined treatments (PReDICT): study protocol for a randomized controlled trial. AB - BACKGROUND: Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impact clinical practice. One major confound in previous studies examining predictors of treatment response is the patient's treatment history, which may affect both the predictor of interest and treatment outcomes. Moreover, prior treatment history provides an important source of selection bias, thereby limiting generalizability. Consequently, we initiated a randomized clinical trial designed to identify factors that moderate response to three treatments for MDD among patients never treated previously for the condition. METHODS/DESIGN: Treatment-naive adults aged 18 to 65 years with moderate-to-severe, non-psychotic MDD are randomized equally to one of three 12 week treatment arms: (1) cognitive behavior therapy (CBT, 16 sessions); (2) duloxetine (30-60 mg/d); or (3) escitalopram (10-20 mg/d). Prior to randomization, patients undergo multiple assessments, including resting state functional magnetic resonance imaging (fMRI), immune markers, DNA and gene expression products, and dexamethasone-corticotropin-releasing hormone (Dex/CRH) testing. Prior to or shortly after randomization, patients also complete a comprehensive personality assessment. Repeat assessment of the biological measures (fMRI, immune markers, and gene expression products) occurs at an early time-point in treatment, and upon completion of 12-week treatment, when a second Dex/CRH test is also conducted. Patients remitting by the end of this acute treatment phase are then eligible to enter a 21-month follow-up phase, with quarterly visits to monitor for recurrence. Non-remitters are offered augmentation treatment for a second 12-week course of treatment, during which they receive a combination of CBT and antidepressant medication. Predictors of the primary outcome, remission, will be identified for overall and treatment specific effects, and a statistical model incorporating multiple predictors will be developed to predict outcomes. DISCUSSION: The PReDICT study's evaluation of biological, psychological, and clinical factors that may differentially impact treatment outcomes represents a sizeable step toward developing personalized treatments for MDD. Identified predictors should help guide the selection of initial treatments, and identify those patients most vulnerable to recurrence, who thus warrant maintenance or combination treatments to achieve and maintain wellness. PMID- 22776544 TI - Does interictal synchronization influence ictogenesis? AB - The EEG recorded from epileptic patients presents with interictal discharges that are not associated with detectable clinical symptoms but are valuable for diagnostic purposes. Experimental studies have shown that interictal discharges and ictal events (i.e., seizures) are characterized intracellularly by similar (but for duration) neuronal depolarizations leading to sustained action potential firing, thus indicating that they may share similar cellular and pharmacological mechanisms. It has also been proposed that interictal discharges may herald the onset of electrographic seizures, but other studies have demonstrated that interictal events interfere with the occurrence of ictal activity. The relationship between interictal and ictal activity thus remains ambiguous. Here we will review this issue in animal models of limbic seizures that are electrographically close to those seen in TLE patients. In particular we will: (i) focus on the electrophysiological and pharmacological characteristics of, at least, two types of interictal discharge; (ii) propose that they play opposite roles in leading to ictogenesis; and (iii) discuss the possibility that mimicking one of these two types of interictal activity by low frequency repetitive stimulation can control ictogenesis. Finally, we will also review evidence indicating that specific types of interictal discharge may play a role in epileptogenesis. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'. PMID- 22776545 TI - Co-learning facilitates memory in mice: a new avenue in social neuroscience. AB - Social context affects brain function but our understanding of its neurobiology is at an early stage. The mere presence of one individual can alter the cognitive capacities of another and social learning has been demonstrated in many species, including the mouse. We asked several questions: 1. How can active engagement of two familiar mice in the same learning activity (co-learning) alter their memory? 2. Under which environmental conditions (aversive vs non-aversive) can we expect the memory to be enhanced, impaired, or not affected? 3. Can a genetic factor modify the co-learning effect on memory? More specifically, can co-learning correct memory deficits in autistic-like BTBR inbred mice with deficient sociability? We demonstrated that pairs of familiar inbred mice of the same or different genotypes (C57BL/6J and BTBR) that were habituated to new objects and their spatial location, had enhanced episodic memory in the spatial object recognition test, whereas individually-trained animals failed to solve this task. Notably, the co-learning effect was genotype-dependent. BTBR mice paired with BTBR cage-mates in the habituation session modestly ameliorated their performance in the object recognition test but co-learning with a familiar C57BL/6J mouse completely normalized episodic memory deficit. Next, we explored the co-learning effect on fear memory in these inbred strains. Interestingly, mice of both genotypes displayed significantly enhanced contextual fear memory once they had been conditioned together with BTBR animals. The same influence of BTBR presence was observed on cued fear memory in C57BL/6J mice, whereas a modest co-learning effect was found on cued fear conditioning in the BTBR strain. Taken together, we demonstrated for the first time the co-learning effect on cognitive capacities in mice, which can be modified by genetic background and environmental conditions. The possible implications of this methodological approach in social neuroscience are discussed. This article is part of a Special Issue entitled 'Cognitive Enhancers'. PMID- 22776546 TI - Tadalafil crosses the blood-brain barrier and reverses cognitive dysfunction in a mouse model of AD. AB - Previous studies have demonstrated that cognitive function can be restored in mouse models of Alzheimer's disease (AD) following administration of sildenafil, a specific PDE5 inhibitor (Puzzo et al., 2009; Cuadrado-Tejedor et al.). Another very potent PDE5 inhibitor with a longer half-life and safe in chronic treatments, tadalafil, may represent a better alternative candidate for AD therapy. However, tadalafil was proven unable to achieve similar benefits than those of sildenafil in AD animal models (Puzzo et al., 2009). The lack of efficacy was attributed to inability to cross the blood-brain barrier (BBB). In this paper we first measured the blood and brain levels of tadalafil to prove that the compound crosses BBB and that chronic treatment leads to accumulation in the brain of the J20 transgenic mouse model of AD. We demonstrated the presence of PDE5 mRNA in the brain of the mice and also in the human brain. After a 10 week treatment with either of these PDE5 inhibitors, the performance of the J20 mice in the Morris water maze test improved when compared with the transgenic mice that received vehicle. Biochemical analysis revealed that neither sildenafil nor tadalafil altered the amyloid burden, although both compounds reduced Tau phosphorylation in the mouse hippocampus. This study provides evidence of the potential benefits of a chronic tadalafil treatment in AD therapy. This article is part of a Special Issue entitled 'Cognitive Enhancers'. PMID- 22776547 TI - Phylogeny, biogeography, and evolution of sex expression in the southern hemisphere genus Leptinella (Compositae, Anthemideae). AB - Leptinella is exceptional in the Anthemideae (Compositae) in its evolution of dimorphic sex expression. A molecular phylogeny including 40 of its 42 described taxa based on nucleotide sequences from two plastid regions (psbA-trnH and trnC petN spacers) and one nuclear marker (nrDNA ITS) is presented. Phylogenetic reconstruction was hampered by inadequate phylogenetic signal indicating recent radiation of species during the last 5 Ma and high level of reticulate evolution presumably caused by hybridisation and polyploidisation. Nevertheless, Leptinella is nested within a paraphyletic genus Cotula that also engulfs the South American genus Soliva. Within Leptinella, the highly polyploid and sexually polymorphic subgenus Leptinella is monophyletic, while subgenus Oligoleima as well as subgenus Radiata are polyphyletic. We found a basal split between a lineage of Australian and New Guinean taxa and one of largely New Zealand taxa. At least five long-distance dispersal events have to be assumed in order to explain the distribution pattern in Leptinella. Among those, one is from New Zealand to Australia, while the others are dispersals to South America and to several subantarctic islands. The phylogeny presented here indicates that the ancestral sex expression in Leptinella is monoecy and that dioecy and paradioecy are derived conditions. High ploidy is especially common in the dioica-group, where dioecy is also common. However, the occurrence of a dioecious sex expression in tetraploid representatives of this group and of polyploidy in other clades that only exhibit monoecious or paradioecious conditions indicate that there is no consistent correlation between these two characters. PMID- 22776548 TI - Diversification in North American arid lands: niche conservatism, divergence and expansion of habitat explain speciation in the genus Ephedra. AB - A lineage of 12 arid land shrubby species in the gymnosperm genus Ephedra (Gnetales) from North America is used to evaluate the influence of climate on speciation. With a long evolutionary history, and a well documented fossil record this lineage is an ideal model for understanding the process of speciation under a niche conservatism scenario. Using seven DNA molecular markers, Bayesian inference is carried out to uncover sister species and to estimate time of divergence of the lineages. Ecological niche models are generated for four parapatric and sympatric sister species and two analyses of niche evolution are performed, one based on ecological niche models and another using raw data and multivariate analysis. As previous analyses suggest, the diversification of North America Ephedra species may be the result of a recent secondary radiation. Both parapatric and sympatric species diverged mostly in a scenario of climatic niche conservatism. However, we also found strong evidence for niche divergence for one of the sister species pairs (E. californica-E. trifurca). Moreover, the multivariate analysis found environmental differences for some variables between sister species. The estimated divergence time of three pairs of sister species distributed in southwestern North America (E. cutleri-E. aspera, E. californica E. trifurca and E. torreyana-E. viridis) is inferred to have occurred in the Late Miocene to Pliocene and for the sister species pair E. antisyphilitica-E. coryi distributed in the southern United States and northeastern Mexico, it was inferred from the Pliocene to Pleistocene. The orogenetic and climatic changes documented for these regions related to expansion of arid lands, may have contributed to the diversification in North American Ephedra, rather than adaptations to new climatic conditions. PMID- 22776549 TI - A mapping of an ensemble of mitochondrial sequences for various organisms into 3D space based on the word composition. AB - To visualize a bird's-eye view of an ensemble of mitochondrial genome sequences for various species, we recently developed a novel method of mapping a biological sequence ensemble into Three-Dimensional (3D) vector space. First, we represented a biological sequence of a species s by a word-composition vector x(s), where its length [absolute value]x(s)[absolute value] represents the sequence length, and its unit vector x(s)/[absolute value]x(s)[absolute value] represents the relative composition of the K-tuple words through the sequence and the size of the dimension, N=4(K), is the number of all possible words with the length of K. Second, we mapped the vector x(s) to the 3D position vector y(s), based on the two following simple principles: (1) [absolute value]y(s)[absolute value]=[absolute value]x(s)[absolute value] and (2) the angle between y(s) and y(t) maximally correlates with the angle between x(s) and x(t). The mitochondrial genome sequences for 311 species, including 177 Animalia, 85 Fungi and 49 Green plants, were mapped into 3D space by using K=7. The mapping was successful because the angles between vectors before and after the mapping highly correlated with each other (correlation coefficients were 0.92-0.97). Interestingly, the Animalia kingdom is distributed along a single arc belt (just like the Milky Way on a Celestial Globe), and the Fungi and Green plant kingdoms are distributed in a similar arc belt. These two arc belts intersect at their respective middle regions and form a cross structure just like a jet aircraft fuselage and its wings. This new mapping method will allow researchers to intuitively interpret the visual information presented in the maps in a highly effective manner. PMID- 22776550 TI - Cascade control of superheated steam temperature with neuro-PID controller. AB - In this paper, an improved cascade control methodology for superheated processes is developed, in which the primary PID controller is implemented by neural networks trained by minimizing error entropy criterion. The entropy of the tracking error can be estimated recursively by utilizing receding horizon window technique. The measurable disturbances in superheated processes are input to the neuro-PID controller besides the sequences of tracking error in outer loop control system, hence, feedback control is combined with feedforward control in the proposed neuro-PID controller. The convergent condition of the neural networks is analyzed. The implementation procedures of the proposed cascade control approach are summarized. Compared with the neuro-PID controller using minimizing squared error criterion, the proposed neuro-PID controller using minimizing error entropy criterion may decrease fluctuations of the superheated steam temperature. A simulation example shows the advantages of the proposed method. PMID- 22776551 TI - Efficacy of reduction therapy of natural human beta-interferon and ribavirin in elderly patients with chronic hepatitis C, genotype 2 and high virus load. AB - AIM: To evaluate the efficacy of natural human interferon (IFN)-beta and ribavirin in elderly patients infected with hepatitis C virus (HCV) genotype 2 and high virus load. METHODS: Inclusion criteria were age of 65 years or older, HCV genotype 2 and serum HCV RNA level of 5.0 logIU/mL or more. A total of 33 were enrolled in this retrospective cohort study. IFN-beta was administrated i.v. at a dose of 6 million units daily for 4 weeks initially, followed by three times a week for 20 weeks. Ribavirin was given daily for 24 weeks at the dose described based on bodyweight. Fifteen patients were given a standard dose of ribavirin (standard group). Eighteen patients were given a reduction dose of ribavirin that decreased by one tablet per day compared to the standard group (reduction group). RESULTS: Of the 33 study patients, no patient stopped the treatment due to treatment-related adverse events. The dose of IFN-beta was reduced in three patients: Two patients belonged to the standard group and one patient belonged to the reduction group. The dose of ribavirin was reduced in 11 patients during combination therapy: nine patients belonged to the standard group and two patients belonged to the reduction group. The sustained virological response (SVR) was 72.2% (13/18) in the reduction group and 80.0% (12/15) in the standard group. There was no significant difference in SVR rate between the reduction and standard groups (P = 0.699). CONCLUSION: The reduction therapy of IFN-beta and ribavirin in elderly chronic hepatitis C patients with genotype 2 and high virus load is one selection of treatment. PMID- 22776552 TI - Hepatitis A outbreak associated with a revolving sushi bar in Chiba, Japan: Application of molecular epidemiology. AB - AIM: The number of hepatitis A cases in Japan as well as in other developed countries has been progressively decreasing during the last several years. There is no universal hepatitis A vaccination program in Japan, and a hepatitis A virus (HAV) epidemic in Japan is not unlikely. In 2011, a hepatitis A outbreak associated with a revolving sushi bar occurred in Chiba, Japan. We aimed to analyze this outbreak. METHODS: Twenty-seven patients associated with this outbreak were admitted to the National Hospital Organization Chiba Medical Center. Molecular epidemiologic investigations were conducted. RESULTS: Twenty six of the 27 patients had gone to the same revolving sushi bar, and then clinical symptoms appeared. HAV RNA was detected by reverse transcription polymerase chain reaction in 23 of the 27 (85.1%) patients whose sera had tested positive for anti-HAV immunoglobulin M. All isolates from this outbreak were clustered within subgenotype IA, displaying 100% sequence homology with each other in 232 bp from all 23 patients. All isolates belong to the IA-1 sublineage, which is endemic to Japan. CONCLUSION: A revolving sushi bar was associated with a hepatitis A outbreak, and molecular epidemiological investigations proved useful. PMID- 22776553 TI - Acute presentation of autoimmune hepatitis in a patient with myasthenia gravis, thymoma, Hashimoto thyroiditis and connective tissue disorder. AB - Myasthenia gravis is an antibody-mediated autoimmune disease at the neuromuscular junctions. It can be associated with many other autoimmune diseases. We report a case of acute presentation of autoimmune hepatitis with myasthenia gravis, thymoma, Hashimoto thyroiditis and connective tissue disorder. PMID- 22776554 TI - E-Rehabilitation - an Internet and mobile phone based tailored intervention to enhance self-management of cardiovascular disease: study protocol for a randomized controlled trial. AB - BACKGROUND: Cardiac rehabilitation is very important for the recovery and the secondary prevention of cardiovascular disease, and one of its main strategies is to increase the level of physical activity. Internet and mobile phone based interventions have been successfully used to help people to achieve this. One of the components that are related to the efficacy of these interventions is tailoring of content to the individual. This trial is studying the effect of a longitudinally tailored Internet and mobile phone based intervention that is based on models of health behaviour, on the level of physical activity and the adherence to the intervention, as an extension of a face-to-face cardiac rehabilitation stay. METHODS/DESIGN: A parallel group, cluster randomized controlled trial. The study population is adult participants of a cardiac rehabilitation programme in Norway with home Internet access and mobile phone, who in monthly clusters are randomized to the control or the intervention condition. Participants have access to a website with information regarding cardiac rehabilitation, an online discussion forum and an online activity calendar. Those randomized to the intervention condition, receive in addition tailored content based on models of health behaviour, through the website and mobile text messages. The objective is to assess the effect of the intervention on maintenance of self-management behaviours after the rehabilitation stay. Main outcome is the level of physical activity one month, three months and one year after the end of the cardiac rehabilitation programme. The randomization of clusters is based on a true random number online service, and participants, investigators and outcome assessor are blinded to the condition of the clusters. DISCUSSION: The study suggests a theory-based intervention that combines models of health behaviour in an innovative way, in order to tailor the delivered content. The users have been actively involved in its design, and because of the use of Open-Source software, the intervention can easily and at low-cost be reproduced and expanded by others. Challenges are the recruitment in the elderly population and the possible underrepresentation of women in the study sample. Funding by Northern Norway Regional Health Authority. TRIAL REGISTRATION: Trial registry http://www.clinicaltrials.gov: NCT01223170. PMID- 22776555 TI - Expression and inhibition of ADAMDEC1 in craniopharyngioma cells. AB - BACKGROUND AND PURPOSE: Craniopharyngioma is a common intracranial tumor characterized by high recurrence rate and poor prognosis in spite of multidisciplinary approaches. The ADAM-like decysin 1 (ADAMDEC1) is a member of a disintegrin and metalloprotease (ADAM) family which correlates with tumor progression and aggressive behavior. This study aimed to detect and inhibit expression of ADAMDEC1 in order to see whether craniopharyngioma cell growth could be suppressed. METHODS: ADAMDEC1 expression was detected by Western Blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). Craniopharyngioma cells, which were obtained from tumor samples after surgical removal, were cultured with or without tamoxifen. MTT assay was used to examine tumor cell growth. RESULTS: ADAMDEC1 mRNA was expressed in craniopharyngioma cell cultures, but it was not shown in normal brain tissue. Tamoxifen not only reduced ADAMDEC1 mRNA and protein expression, but also inhibited craniopharyngioma cell proliferation. CONCLUSIONS: ADAMDEC1 may serve as a novel marker for craniopharyngiomas, and tamoxifen could inhibit craniopharyngioma cell growth and ADAMDEC1 expression. PMID- 22776556 TI - Reliability of computer designed surgical guides in six implant rehabilitations with two years follow-up. AB - OBJECTIVE: To evaluate the reliability and accuracy of computer-designed surgical guides in osseointegrated oral implant rehabilitation. MATERIALS AND METHODS: Six implant rehabilitations, with a total of 17 implants, were completed with computer-designed surgical guides, performed with the master model developed by muco-compressive and muco-static impressions. In the first case, the surgical guide had exclusively mucosal support, in the second case exclusively dental support. For all six cases computer-aided surgical planning was performed by virtual analyses with 3D models obtained by dental scan DICOM data. The accuracy and stability of implant osseointegration over two years post surgery was then evaluated with clinical and radiographic examinations. Radiographic examination, performed with digital acquisitions (RVG - Radio Video graph) and parallel techniques, allowed two-dimensional feedback with a margin of linear error of 10%. RESULTS: Implant osseointegration was recorded for all the examined rehabilitations. During the clinical and radiographic post-surgical assessments, over the following two years, the peri-implant bone level was found to be stable and without appearance of any complications. The margin of error recorded between pre-operative positions assigned by virtual analysis and the post-surgical digital radiographic observations was as low as 0.2mm. SIGNIFICANCE: Computer guided implant surgery can be very effective in oral rehabilitations, providing an opportunity for the surgeon: (a) to avoid the necessity of muco-periosteal detachments and then (b) to perform minimally invasive interventions, whenever appropriate, with a flapless approach. PMID- 22776557 TI - Stimulation of a pulse of LH and reduction in PRL concentration by a physiologic dose of GnRH before, during, and after luteolysis in heifers. AB - A single physiologic dose (5.0 MUg) of GnRH was given to 9 heifers each day (Hour 0) beginning on Day 15 postovulation until regression of the corpus luteum. Blood samples were taken each day for Hours -3, -2, -1, 0, 0.25, 0.5, 0.75, 1, 1.25, 1.50, 1.75, 2, 3, 4, and 5. Based on daily progesterone concentrations, data were grouped into phases of before (n=4), during (n=8), and after (n=7) luteolysis. The number of LH pulses with a peak at pretreatment Hours -2 or -1 (0.35 +/- 0.12 pulses/sampling session) was less (P<0.0001) than for a pulse peak at posttreatment Hours 1 or 2 (1.0 +/- 0.0 pulses/session). The characteristics and effects of LH pulses on progesterone and estradiol were similar between natural (pretreatment) and primarily induced (posttreatment) LH pulses. The same dose of GnRH stimulated an LH pulse with greater (P<0.05) amplitude after luteolysis than during luteolysis. Concentrations of PRL and number and prominence of PRL pulses decreased (P<0.05) between Hours 0 and 2 within each of the phases of before, during, and after luteolysis. The hypothesis that a physiologic dose of GnRH increases the concentration of PRL was not supported; instead, GnRH reduced the concentration of PRL. Results supported the hypotheses that an appropriate dose of GnRH stimulates an LH pulse during luteolysis that is similar to a natural pulse in characteristics and in the effects on progesterone and estradiol. PMID- 22776558 TI - Motile sperm subpopulations in frozen-thawed dog semen: changes after incubation in capacitating conditions and relationship with sperm survival after osmotic stress. AB - In this study we investigated the changes that in vitro incubation under capacitating conditions could induce on the motile sperm subpopulations present in frozen-thawed dog semen samples. In addition, cryopreserved dog spermatozoa were exposed to CCM (canine capacitating medium) solutions of 300, 150, 100 and 75 mOsm and the proportions of live spermatozoa with swollen tails were recorded (HOST+). Finally, frozen-thawed dog semen samples were submitted to a second cycle of freezing and thawing and the overall sperm motility, as well as the motile sperm subpopulations structure, was determined. Cryopreserved dog semen samples were structured in four sperm subpopulations with different motility characteristics: Subpopulation (Sp) 1 contained moderately rapid and progressive spermatozoa (25.2 +/- 8.5%), Sp 2 included poorly motile and non progressive sperm (15.3 +/- 8.1%), Sp 3 was represented by moderately slow non progressive sperm (14.9 +/- 5.9%), and Sp 4 contained the most rapid and progressive sperm (20.8 +/- 14.7%). After 3h of incubation under capacitating conditions, percentages of spermatozoa assigned to Sp 2 (6.1 +/- 3.4%) and 3 (4.9 +/- 2.8%) significantly decreased, whereas those assigned to Sp 1 (17.0 +/- 11.2%) and 4 (16.2 +/- 12.8%) did not significantly change. Significant correlations were found between percentages of HOST+, for the 3 osmolarities tested, and percentages of spermatozoa included in Sp 1 and 4 after 3 h of incubation in capacitating conditions or in Sp 4 after double freezing and thawing. These results indicated that subpopulations with the most rapid and progressive sperm seemed to be highly resistant to in vitro incubation in capacitating conditions and to osmotic stress, suggesting they are likely to be the source of the fertilizing population. PMID- 22776559 TI - Copper-selective electrochemical filling of macropore arrays for through-silicon via applications. AB - In this article, the physico-chemical and electrochemical conditions of through silicon via formation were studied. First, macropore arrays were etched through a low doped n-type silicon wafer by anodization under illumination into a hydrofluoric acid-based electrolyte. After electrochemical etching, 'almost' through-silicon macropores were locally opened by a backside photolithographic process followed by anisotropic etching. The 450 * 450-MUm2 opened areas were then selectively filled with copper by a potentiostatic electrochemical deposition. Using this process, high density conductive via (4.5 * 105 cm-2) was carried out. The conductive paths were then electrically characterized, and a resistance equal to 32 mOmega/copper-filled macropore was determined. PMID- 22776561 TI - Biological significance of HORMA domain containing protein 1 (HORMAD1) in epithelial ovarian carcinoma. AB - The present study was undertaken to determine the expression and biological significance of HORMAD1 in human epithelial ovarian carcinoma. We found that a substantial proportion of human epithelial ovarian cancers expressed HORMAD1. In vitro, HORMAD1 siRNA enhanced docetaxel induced apoptosis and substantially reduced the invasive and migratory potential of ovarian cancer cells (2774). In vivo, HORMAD1 siRNA-DOPC treatment resulted in reduced tumor weight, which was further enhanced in combination with cisplatin. HORMAD1 gene silencing resulted in significantly reduced VEGF protein levels and microvessel density compared to controls. Our data suggest that HORMAD1 may be an important therapeutic target. PMID- 22776560 TI - Mammary fibroblasts regulate morphogenesis of normal and tumorigenic breast epithelial cells by mechanical and paracrine signals. AB - Stromal factors play a critical role in the development of the mammary gland. Using a three dimensional-coculture model we demonstrate a significant role for stromal fibroblasts in the regulation of normal mammary epithelial morphogenesis and the control of tumor growth. Both soluble factors secreted by fibroblasts and fibroblast-derived modifications of the matrix compliance contribute to the regulation of epithelial cell morphogenesis. Readjustment of matrix tension by fibroblasts can even induce a phenotypic reversion of breast carcinoma cells. These data offer a basis to develop new strategies for the normalization of the tumor stroma as an innovative target in cancer therapy. PMID- 22776562 TI - Pulling the plug on a cancer cell by eliminating XIAP with AEG35156. AB - XIAP, the X-linked inhibitor of apoptosis, is the best example of an endogenous cellular suppressor of apoptosis. XIAP is effective because it directly limits the activity of several critical death-inducing caspases, notably caspase-3, -7 and -9, either by direct enzyme inhibition or through ubiquitin-mediated proteasomal degradation. Furthermore, XIAP acts simultaneously at several nodes in the apoptotic cascade, blocking both the intrinsic and extrinsic death pathways, and thereby preventing feed-forward amplification loops that would otherwise lead to cell death. XIAP over-expression, or increased activity, is associated with cancer progression, resistance to therapy and poor prognosis. Targeting XIAP gene expression by antisense oligonucleotides, or other approaches, demonstrates anti-cancer effects with XIAP down-regulation. These early preclinical studies led to the development of a clinical candidate mixed backbone antisense oligonucleotide, AEG35156, against XIAP for the treatment of cancer. Published clinical results for the first-in-class and first-in-human trials of AEG35156 are summarized herein, including single agent and combination chemotherapy phase-I or -II trials for solid tumors, lymphoma, and acute myeloid leukemia. These trials demonstrate the safety of AEG35156, as well as some initial promising signs of anti-cancer activity. PMID- 22776563 TI - Hyaluronic acid-coated nanostructured lipid carriers for targeting paclitaxel to cancer. AB - The aim of our study was to develop hyaluronic acid-coated, paclitaxel-loaded, nanostructured lipid carriers (HA-NLCs) prepared via electrostatic attraction for delivering paclitaxel (PTX) to tumors overexpressing CD44. First, cationic PTX NLC was prepared by melt emulsion technology. Then, PTX-NLC were coated with hyaluronic acid (HA). The in vitro release of PTX was evaluated by the dialysis method. This analysis showed that PTX was released more slowly from HA-NLC than from Taxol(r). The in vitro cytotoxicity of HA-NLC was investigated using the MTT method in B16, CT26 and HCT116 cell lines. The results showed that the cytotoxicity of HA-NLC against these three cancer cell lines was superior to that of Taxol(r). The in vivo antitumor effect, the pharmacokinetics and the tissue distribution of HA-NLC were all evaluated in B16-bearing Kunming mice. The results showed that HA-NLC was better tolerated and had increased antitumor activity in B16-bearing Kunming mice compared with Taxol(r). Furthermore, HA-NLC could prolong the circulation time of PTX in blood and increase the accumulation of PTX in the tumor. Therefore, HA-NLC prepared via electrostatic attraction was an effective carrier for delivering PTX to tumors overexpressing CD44. PMID- 22776564 TI - Estimating the re-identification risk of clinical data sets. AB - BACKGROUND: De-identification is a common way to protect patient privacy when disclosing clinical data for secondary purposes, such as research. One type of attack that de-identification protects against is linking the disclosed patient data with public and semi-public registries. Uniqueness is a commonly used measure of re-identification risk under this attack. If uniqueness can be measured accurately then the risk from this kind of attack can be managed. In practice, it is often not possible to measure uniqueness directly, therefore it must be estimated. METHODS: We evaluated the accuracy of uniqueness estimators on clinically relevant data sets. Four candidate estimators were identified because they were evaluated in the past and found to have good accuracy or because they were new and not evaluated comparatively before: the Zayatz estimator, slide negative binomial estimator, Pitman's estimator, and mu-argus. A Monte Carlo simulation was performed to evaluate the uniqueness estimators on six clinically relevant data sets. We varied the sampling fraction and the uniqueness in the population (the value being estimated). The median relative error and inter quartile range of the uniqueness estimates was measured across 1000 runs. RESULTS: There was no single estimator that performed well across all of the conditions. We developed a decision rule which selected between the Pitman, slide negative binomial and Zayatz estimators depending on the sampling fraction and the difference between estimates. This decision rule had the best consistent median relative error across multiple conditions and data sets. CONCLUSION: This study identified an accurate decision rule that can be used by health privacy researchers and disclosure control professionals to estimate uniqueness in clinical data sets. The decision rule provides a reliable way to measure re identification risk. PMID- 22776565 TI - Evaluation of the Essen Rotary as a new technique for bacterial swabs: results of a prospective controlled clinical investigation in 50 patients with chronic leg ulcers. AB - Most chronic wounds are colonised with different microorganisms, especially problematic bacteria like methicillin-resistant Staphylococcus aureus (MRSA), which represent an increasing therapeutic challenge in the modern wound therapy regimen. Therefore, it is essential to specify the bacteria in wounds for an individual-specific treatment. In most patients, an exemplary bacterial swab is taken from the centre of the wound surface. This so-called Levine technique is propagated currently as the gold standard. The aim of our clinical investigation was to compare the results of different swab techniques to the new established Essen Rotary. In this monocentric prospective investigation, 50 patients with chronic leg ulcers were examined consecutively. The results of our clinical study show that bacteria are heterogeneously spread on wound surfaces. The analysis of the semiquantitative measured results showed that the Essen Rotary could detect significant more bacteria with a total amount of 111 bacteria (P = 0.049) compared to usual swab techniques. Considerably, only the Essen Rotary identified five compared to three MRSA-patients detected by other techniques. The Essen Rotary is an efficient, economic and uncomplicated modification of bacteriological swab techniques which detects significant more bacteria compared to other conventional swab techniques. Therefore, the Essen Rotary may become the new gold standard in routinely taken bacteriological swabs especially for MRSA screenings in patients with chronic leg ulcers. PMID- 22776566 TI - Development and validation of IIKC: an interactive identification key for Culicoides (Diptera: Ceratopogonidae) females from the Western Palaearctic region. AB - BACKGROUND AND METHODS: The appearance of bluetongue virus (BTV) in 2006 within northern Europe exposed a lack of expertise and resources available across this region to enable the accurate morphological identification of species of Culicoides Latreille biting midges, some of which are the major vectors of this pathogen. This work aims to organise extant Culicoides taxonomic knowledge into a database and to produce an interactive identification key for females of Culicoides in the Western Palaearctic (IIKC: Interactive identification key for Culicoides). We then validated IIKC using a trial carried out by six entomologists based in this region with variable degrees of experience in identifying Culicoides. RESULTS: The current version of the key includes 98 Culicoides species with 10 morphological variants, 61 descriptors and 837 pictures and schemes. Validation was carried out by six entomologists as a blind trial with two users allocated to three classes of expertise (beginner, intermediate and advanced). Slides were identified using a median of seven steps and seven minutes and user confidence in the identification varied from 60% for failed identifications to a maximum of 80% for successful ones. By user class, the beginner group successfully identified 44.6% of slides, the intermediate 56.8% and the advanced 74.3%. CONCLUSIONS: Structured as a multi-entry key, IIKC is a powerful database for the morphological identification of female Culicoides from the Western Palaearctic region. First developed for use as an interactive identification key, it was revealed to be a powerful back-up tool for training new taxonomists and to maintain expertise level. The development of tools for arthropod involvement in pathogen transmission will allow clearer insights into the ecology and dynamics of Culicoides and in turn assist in understanding arbovirus epidemiology. PMID- 22776568 TI - Poor quality of antenatal care services--is lack of competence and support the reason? An observational and interview study in rural areas of Lao PDR. AB - OBJECTIVE: to explore the health-care providers' performance and their own perceptions of the ANC services they provide. DESIGN, SETTING AND PARTICIPANTS: this cross-sectional exploratory survey was carried out in 2009 at four district hospitals and 18 health centres in Khammouane and Champasack provinces in rural areas of Laos. MEASUREMENTS AND FINDINGS: combinations of quantitative and qualitative methods were used: (i) 59 observations of ANC sessions (components performed and equipment used); (ii) 26 semi-structured interviews with health care providers engaged in ANC services, interpreted through content analysis. The findings indicated an overall poor quality and performance of ANC services in rural health facilities with lack of routines, scarce or insufficient equipment and limited skills among providers. The health-care providers gave an often pessimistic picture of their competence and motivation to work with ANC. Some articulated a resignation due to lack of feedback from the patients and they expressed a need for support from health-care superiors. Compared to the district hospitals, the health centres were less well-equipped and supplied, and the providers had a heavier workload, because all activities including ANC were carried out by the same provider. The average consultation time for each woman was 5mins. CONCLUSIONS: the quality of ANC services in rural health facilities in Laos was poor due to lack of resources, the providers' limited skills concurrent with inadequate routines and insufficient backup from superiors. IMPLICATIONS FOR PRACTICE: to comply with national and international recommendations for ANC services, our suggestion is to improve the quality of the rural health facilities in Laos by providing basic equipment, support from experienced superiors and in service training. PMID- 22776569 TI - Elective induction of labour: the problem of interpretation and communication of risks. PMID- 22776570 TI - Two-stage hypospadias repair with inner preputial layer Wolfe graft (Aivar Bracka repair). PMID- 22776567 TI - The optimized acupuncture treatment for neck pain caused by cervical spondylosis: a study protocol of a multicentre randomized controlled trial. AB - BACKGROUND: Neck pain is one of the chief symptoms of cervical spondylosis (CS). Acupuncture is a well-accepted and widely used complementary therapy for the management of neck pain caused by CS. In this paper, we present a randomized controlled trial protocol evaluating the use of acupuncture for CS neck pain, comparing the effects of the optimized acupuncture therapy in real practice compared with sham and shallow acupuncture. METHODS/DESIGN: This trial uses a multicentre, parallel-group, randomized, sham acupuncture and shallow acupuncture, controlled single-blind design. Nine hospitals are involved as trial centres. 945 patients who meet inclusion criteria are randomly assigned to receive optimized acupuncture therapy, sham acupuncture or shallow acupuncture by a computerized central randomization system. The interventions past for 4 weeks with eight to ten treatments in total. The group allocations and interventions are concealed to patients and statisticians. The Northwick Park Neck Pain Questionnaire (NPQ) is used as the primary outcome measure, and the McGill Pain Questionnaire (MPQ) and The Short Form (36) Health Survey (SF-36) are applied as secondary outcome measures. The evaluation is performed at baseline, at the end of the intervention, and at the end of the first month and the third month during follow-up. The statistical analyses will include baseline data comparison and repeated measures of analysis of variance (ANOVA) for primary and secondary outcomes of group and time differences. Adverse events (AEs) will be reported if they occur. DISCUSSION: This trial is a multicentre randomized control trial (RCT) on the efficacy of acupuncture for CS neck pain and has a large sample size and central randomization in China. It will strictly follow the CONSORT statement and STRICTA extension guideline to report high-quality study results. By setting the control groups as sham and shallow acupuncture, this study attempts to reveal the effects of real acupuncture versus placebo or non-classic acupuncture treatment and evaluate whether classic Chinese medical acupuncture is effective on CS neck pain. This study will provide evidence for the effects of acupuncture on CS neck pain. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC 00000184. PMID- 22776571 TI - Single-stage reconstruction of complex anterior urethral strictures using overlapping dorsal and ventral buccal mucosal grafts. PMID- 22776572 TI - Boyle and hill's circumcision 'Phallusies'. PMID- 22776573 TI - Penile Doppler sonographic and clinical characteristics in Peyronie's disease and/or erectile dysfunction: an analysis of 1500 men with sexual dysfunction. PMID- 22776575 TI - Paul Epstein (1943-2011): a life of commitment to health and social justice. PMID- 22776576 TI - Migrant farmworker housing. PMID- 22776577 TI - The sustainability solutions agenda. AB - Progress toward a more sustainable society is usually described in a "knowledge first" framework, where science characterizes a problem in terms of its causes and mechanisms as a basis for subsequent action. Here we present a different approach-A Sustainability Solutions Agenda (SSA)-which seeks from the outset to identify the possible pathways to solutions. SSA focuses on uncovering paths to sustainability by improving current technological practice, and applying existing knowledge to identify and evaluate technological alternatives. SSA allows people and organizations to transition toward greater sustainability without sacrificing essential technological functions, and therefore does not threaten the interests that depend on those functions. Whereas knowledge-first approaches view scientific information as sufficient to convince people to take the right actions, even if those actions are perceived as against their immediate interests, SSA allows values to evolve toward greater attention to sustainability as a result of the positive experience of solving a problem. PMID- 22776578 TI - Safety, security, hygiene and privacy in migrant farmworker housing. AB - Safety, security, hygiene, and privacy in migrant farmworker housing have not previously been documented, yet these attributes are important for farmworker quality of life and dignity. This analysis describes the safety, security, hygiene, and privacy of migrant farmworker housing and delineates camp characteristics that are associated with these attributes, using data collected in 183 eastern North Carolina migrant farmworker camps in 2010. Migrant farmworker housing is deficient. For example, 73.8 percent of housing had structural damage and 52.7 percent had indoor temperatures that were not safe. Farmworkers in 83.5 percent of the housing reported that they did not feel they or their possessions were secure. Bathing or toileting privacy was absent in 46.2 percent of the housing. Camps with residents having H-2A visas or North Carolina Department of Labor certificates of inspection posted had better safety, security, and hygiene. Regulations addressing the quality of migrant farmworker housing are needed. PMID- 22776579 TI - Employer provision of personal protective equipment to Latino workers in North Carolina residential construction. AB - Despite federal regulations requiring provision of personal protective equipment (PPE) without cost to workers in the United States, very little is known about whether immigrant Latino construction workers receive no-cost PPE from their employers, and the role that employer provision plays in regular use of PPE. This study used cross-sectional data from a community-based sample of 119 Latino construction workers in western North Carolina to document receipt of employer provided PPE by construction workers, investigate sources of variation in the receipt of employer-paid PPE, and delineate associations of employer-paid PPE with workers' regular use of PPE. The results suggest that the residential construction subsector generally fails to provide workers with PPE at no cost, as is required by regulation. Analyses also suggest that recent immigrants are least likely to receive no-cost, employer-provided PPE, and that when employers do provide no-cost PPE, Latino construction workers are more likely to use it regularly. PMID- 22776580 TI - A collaborative effort to address the distribution of plutonium-contaminated sludge in Livermore, California. AB - Plutonium releases from the U.S. nuclear weapons laboratory in Livermore, California resulted in the contamination of sewage sludge. Two research models to address the potential public health impacts of plutonium-contaminated sludge distribution were undertaken. One model was a collaborative approach that emphasized incorporating local knowledge into the scientific analysis and fostering the growth of mutually respectful relationships between scientists, governmental, and non-governmental collaborators. The second was a dose assessment approach that utilized existing data to estimate radiological doses from exposure to plutonium contaminated sewage sludge and compared the estimated doses with those that have caused sickness or death. The two models reached different conclusions; neither addressed issues of intergenerational equity and primary prevention of exposure. Advancing an ethical research agenda will involve looking upstream of the contamination and working toward sustainable solutions to security that do not involve the public health threats embedded in the global embrace of nuclear weapons. PMID- 22776581 TI - A complaint from Citizens for Sludge-Free Land. PMID- 22776582 TI - North Carolina's Farmworker Advocacy Network demands a Harvest of Dignity. PMID- 22776583 TI - Health disparities or inequality? PMID- 22776588 TI - Roots and fungi accelerate carbon and nitrogen cycling in forests exposed to elevated CO2. AB - A common finding in multiple CO(2) enrichment experiments in forests is the lack of soil carbon (C) accumulation owing to microbial priming of 'old' soil organic matter (SOM). However, soil C losses may also result from the accelerated turnover of 'young' microbial tissues that are rich in nitrogen (N) relative to bulk SOM. We measured root-induced changes in soil C dynamics in a pine forest exposed to elevated CO(2) and N enrichment by combining stable isotope analyses, molecular characterisations of SOM and microbial assays. We find strong evidence that the accelerated turnover of root-derived C under elevated CO(2) is sufficient in magnitude to offset increased belowground inputs. In addition, the C losses were associated with accelerated N cycling, suggesting that trees exposed to elevated CO(2) not only enhance N availability by stimulating microbial decomposition of SOM via priming but also increase the rate at which N cycles through microbial pools. PMID- 22776591 TI - Choline reverses scopolamine-induced memory impairment by improving memory reconsolidation. AB - It is widely known that pre-training systemic administration of the muscarinic antagonist scopolamine (SCP) (0.5mg/kg, i.p.) leads to anterograde memory impairment in retention tests. The administration of the alpha(7)-nicotinic receptor agonist choline (Ch) in the dorsal hippocampus (0.8MUg/hippocampus) immediately after memory reactivation allowed recovery from scopolamine-induced memory impairment. This effect of Ch was time-dependent, and retention performance was not affected in drug-treated mice that were not subjected to memory reactivation, suggesting that the performance effects are not due to non specific effects of the drug. The effects of Ch also depended on the age of the reactivated memory. Altogether, our results suggest that Ch exerts its effects by modulating memory reconsolidation, and that the memory impairment induced by low doses of SCP is a memory expression failure and not a storage deficit. Therefore, reconsolidation, among other functions, might serve to change memory expression in later tests. Summarizing, our results open new avenues about the behavioral significance and the physiological functions of memory reconsolidation, providing new strategies for recovering memories from some types of amnesia. PMID- 22776592 TI - [Application of intraoperative spinal ultrasonography in thoracic spinal decompressive operations]. AB - OBJECTIVE: To investigate the feasibility and clinical value of intraoperative ultrasonography (IOUS) in thoracic spinal decompression surgery. METHODS: Ten patients with confirmed thoracic spinal stenosis underwent thoracic spinal decompression in our center from August 2009 to December 2010. The appearance of the compressed section of spinal cord was observed with IOUS. Before and after the decompression operation, the diameters of dural sac and the spinal cord were recorded respectively. The location and nature of the compression-causing mass were confirmed. RESULTS: IOUS clearly showed the shape of the normal and the compressed sections of dural sac and spinal cord. In the 14 thoracic spinal cord sections of these 10 patients, the anteroposterior diameter, horizontal diameter, and their ratio were bigger than those before decompression. The values of anteroposterior diameter and anteroposterior/horizontal diameter ratio showed significant differences(the P value of dural sac anteroposterior diameter comparison was 0.008, which of spinal cord was 0.007; the P values of these two structures ratio comparison were both 0.002 before and after decompression), while the horizontal diameter presented no significant differences (the P values of both structures were 0.270 and 0.195 respectively before and after decompression). CONCLUSIONS: IOUS can clearly show the morphological changes of the dural sac and spinal cord before and after the decompression. In addition, it helps surgeons to locate and specify the nature of the compression-causing mass on the ventral side of dural sac. Furthermore, IOUS can suggest whether the decompression is sufficient in a real-time manner. PMID- 22776593 TI - [CT findings of ovarian fibroma in 9 patients]. AB - OBJECTIVE: To study the value of multislice spiral computed tomography (CT) in the diagnosis of ovarian fibroma. METHOD: The CT findings of 9 cases with pathologically confirmed ovarian fibroma were retrospectively analyzed by two radiologists. RESULTS: All of the 9 cases showed unilateral adnexal mass with demarcated boundary. There were three different types of ovarian fibroma according to the CT appearances simple type(n=4), degeneration type(n=3) and the ovarian fibroma with ascites(n=2). The simple type showed homogeneous-density solid tumor with no enhancement; two of them diagnosed as uterine leiomyomas and the other two as benign tumor originated from the ovary. The degeneration type showed irregular or round hypodensity inside the tumor with no enhancement; one of them was diagnosed as malignant tumor and the other two as intrapelvic mass. The ovarian fibroma with ascites showed homogeneous density with no enhancement; one with ascites and pelvic effusion and the other one with pleural effusion, ascites and pelvic effusion, both of whom were diagnosed as malignant tumor that possibly originated from the ovary. CONCLUSIONS: The ovarian fibroma has diverse CT findings. They often appear as a unilateral adnexal solid tumor without obvious enhancement. A diagnosis of Meigs's syndrome may be made when it is accompanied with ascites and pleural effusion. PMID- 22776594 TI - [Creation of an animal model for post-operative adhesion prevention]. AB - OBJECTIVE: To establish a rabbit double uterine horn model for assessing the time course of pelvic adhesions and evaluating the effectiveness of different anti adhesive materials in reducing adhesions. METHODS: A total of 330 Japanese white rabbits underwent laparotomy, followed by uterine horn incision. Animals were euthanized after 3, 7, 14, 28, and 42 days, respectively. RESULTS: The surgical procedure was smooth. Rabbit double uterine horn model was applied for the evaluation of pelvic adhesions in a three-dimension fashion. Each of the three means-gauze abrasion, needle holder clamping, and direct uterine incision induced postoperative pelvic adhesions, among which direct uterine incision was the best to mimic conditions after gynecological operations. Under normal circumstances, degradation of filmy fibrinous adhesions by locally released proteases of the fibrinolytic system occurred within 3 days of injury. The regeneration of the mesothelium was completed within 7 days. Collagen reached its peak by day 14. Anti-adhesive materials were supposed to be completely absorbed by day 28, and their effectiveness in preventing pelvic adhesions was confirmed at this time point. Whether their effect can be maintained after the absorption of the anti adhesive materials was investigated in 42 days. CONCLUSIONS: The animal model was successfully established. It well mimics the postoperative pelvic adhesions after direct uterine horn injury and thus is a suitable model for studying site specific adhesions. Observations on the 3rd, 7th, 14th, 28th, and 42nd post operative days provided a full picture of the adhesion formation process. PMID- 22776590 TI - Ferritin above 100 mcg/L could rule out colon cancer, but not gastric or rectal cancer in patients with involuntary weight loss. AB - BACKGROUND: A tenth of patients with involuntary weight loss (IWL) have gastrointestinal cancer. Ferritin is the first parameter to be modified during the process leading to iron deficiency anaemia, therefore it should be the most sensitive. The aim of this study was to assess the ability of ferritin to rule out gastrointestinal cancer in patients with involuntary weight loss. METHODS: All consecutive patients with IWL admitted in a secondary care university hospital were prospectively studied. Ferritin, haemoglobin with erythrocyte indices and serum iron were recorded for all patients. The reference standard was bidirectional endoscopy and/or 6 months follow-up. RESULTS: 290 patients were included, a quarter had cancer, of which 22 (7.6%) had gastrointestinal cancer (8 gastric cancer, 1 ileum cancer, 13 colorectal cancer). Ferritin had the best area under the curve (AUC), both for gastrointestinal cancer (0.746, CI: 0.691-0.794), and colorectal cancer (0.765, CI: 0.713-0.813), compared to the other parameters of iron deficiency. In the diagnosis of colorectal cancer, ferritin with a cut off value of 100 mcg/L had a sensitivity of 93% (CI: 69-100%), and negative likelihood ratio of 0.13, with a negative predictive value of 99% (96-100%), while for gastrointestinal cancer, the sensitivity was lower (89%, CI: 67-95%), with a negative likelihood ratio of 0.24. There were three false negative patients, two with gastric cancer, and one with rectal cancer. CONCLUSION: In patients with involuntary weight loss, a ferritin above 100mcg/L could rule out colon cancer, but not gastric or rectal cancer. PMID- 22776595 TI - [Item selection analysis based on quality of life scale in patients with viral myocarditis]. AB - OBJECTIVE: To further select the items based on the pre-test version of quality of life scale in patients with viral myocarditis. METHODS: Totally 100 patients with viral myocarditis were enrolled in this study. Methodologies including frequency distribution, discrete trend, t-test, Cronbach's alpha coefficient, correlation coefficient and factor analysis were applied to select items from different perspectives. RESULTS: A total of 17 items were selected by frequency distribution method from the perspective of central tendency, 15 items were selected by discrete trend method from the perspective of sensitivity, 16 items were selected by t-test method from the perspective of sensitivity and discrimination, 16 items were selected by Cronbach's alpha coefficient method from the perspective of internal consistency, 12 items were selected by correlation coefficient method from the perspective of representation and independence, and 18 items were selected by factor analysis method from the perspective of representation. CONCLUSION: Item selection of quality of life scale in patients with viral myocarditis was successfully conducted based on the clinical epidemiological data using a variety of statistical methods. PMID- 22776596 TI - [The in-vitro effects of arbidol hydrochloride against 2009 new influenza virus A (H1N1)]. AB - OBJECTIVE: To detect the in-vitro effects of arbidol hydrochloride against 2009 new influenza virus A (H1N1). METHODS: The activity of arbidol hydrochloride against 2009 new influenza virus A (H1N1) was determined in MDCK cell cultures. Hemagglutination assay, observation of cytopathic effects, RT-PCR and quantitative RT-PCR tests were performed for determination of virus titers. Inhibition concentration 50% and cytotoxic concentration 50% were calculated with Chou's Menu of Dose-Effect Program. RESULTS: Arbidol hydrochloride showed low cytotoxicity (cytotoxic concentration 50%>100 MUmol/L)and significant anti-2009 new influenza virus A (H1N1) activity in cell cultures. Inhibition concentration 50% were (5.5 +/- 0.9), (3.4 +/- 0.8), and (1.5 +/- 0.2) MUmol/L in hemagglutination assay, cytopathic effect test, and quantitative RT-PCR assay, respectively. CONCLUSION: Arbidol has low cytotoxicity and high anti-virus activity and can effectively trigger the activities of interferon and immune response, and therefore can be a valuable anti-influenza virus drug. PMID- 22776597 TI - [Correlation between blood eosinophil level and steroid doses in patients with bullous pemphigoid]. AB - OBJECTIVE: To evaluate the correlation between blood eosinophil (EOS)level and steroid doses in patients of bullous pemphigoid (BP). METHODS: A total of 82 untreated BP inpatients (n=49) and outpatients (n=33) were enrolled in this study. The blood EOS level and the steroid doses before and after treatment were recorded. The correlation between EOS level and steroid doses was analyzed retrospectively. RESULTS: EOS increased in 69 BP patients (84.15%); on the contrary, only 10% of normal controls had increased EOS (t=1.99,P<0.001). In 44 inpatients, the blood EOS remained high before steroid treatment, and quickly returned to normal level after the disease became stable. There was a linear correlation between EOS and steroid doses (Spearman analysis,r=0.496,P<0.001). In 5 patients who were treated by non-steroid approach, EOS level also declined after the disease was resolved. CONCLUSION: EOS can be one of useful indicators for the application of steroids in the treatment of BP. PMID- 22776598 TI - [Establishment of a rat model of low calcium diet related hyperoxaluria]. AB - OBJECTIVE: To establish a rat model of low calcium diet related hyperoxaluria and explore its features. METHODS: By means of randomized blocks design, totally 24 SD male rats were divided into low calcium diet group, medium calcium diet group, and high calcium diet group. Each group was sequentially fed on different calcium diets for 3 days. The urinary volume within 24 hours was recorded, the consistency of urinary oxalate by high-efficiency liquid chromatography, and the consistency of urine creatinine by automatic biochemical analyzer. The consistency was corrected to the output of urinary oxalate of rats in 24 hours, and the results were evaluated by repeated measurement of variance analysis and multivariate analysis of variance. RESULTS: The output of urinary oxalate of rats in 24 hours varied with time (F=7.893, P0.05). The output of urinary oxalate of rats in 24 hours varied with group division (F=3.565, P<0.05). The output of urinary oxalate in 24 hours in three groups on the third day was significantly higher than that on the first day (P<0.05). CONCLUSION: By controlling the calcium intake, we successfully established the model of low calcium diet related hyperoxaluria in rat. PMID- 22776599 TI - [Value of 3T magnetic resonance dynamic contrast-enhanced and diffusion-weighted imaging in differential diagnosis of musculoskeletal tumors]. AB - OBJECTIVE: To evaluate the value of magnetic resonance dynamic contrast-enhanced (MR-DCE) and magnetic resonance diffusion-weighted imaging (MR-DWI) in the differentiation of benign and malignant musculoskeletal tumors. METHODS: Sixty three patients with pathologically confirmed musculoskeletal tumors were examined with MR-DCE and MR-DWI. Using single shot spin echo planar imaging sequence and different b values of 400, 600, 800 and 1000 s/mm(2), we obtained the apparent diffusion coefficient (ADC) of the lesions. ADC values were measured before and after MR-DCE, with a b value of 600 s/mm(2). The 3D fast acquired multiple phase enhanced fast spoiled gradient recalled echo sequence was obtained for multi slice of the entire lesion. The time-signal intensity curve (TIC), dynamic contrast-enhanced parameters, maximum slope of increase (MSI), positive enhancement integral, signal enhancement ratio, and time to peak (T(peak)) were also recorded. RESULTS: ADC showed no significant difference between benign and malignant tumors when the b value was 400, 600, 800, or 1000 s/mm(2), and it was not significantly different between benign and malignant tumors in both pre-MR DCE and post-MR-DCE with b value of 600 s/mm(2). TIC were classified into four types type1 showed rapid progression and gradual drainage; type2 showed rapid progression but had no or slight progression; type 3 showed gradual progression; and type 4 had no or slight progression. Most lesions of type1 or type2 were malignant, whereas most lesions of type 3 or type 4 were benign. When using type1 and type 2 as the standards of malignancy, the diagnostic sensitivity and specificity was 87.23% and 50.00%, respectively. The types of TIC showed significant difference between benign and malignant musculoskeletal tumors(chi(2)=17.009,P=0.001). When using MSI 366.62 +/- 174.84 as the standard of malignancy, the diagnostic sensitivity and specificity was 86.78% and 78.67%, respectively. When using T(peak)<=70s as the standard of malignancy, the diagnostic sensitivity and specificity was 82.89%and 85.78%, respectively. Positive enhancement integral and signal enhancement ratio showed no significant difference between benign and malignant musculoskeletal tumors. CONCLUSIONS: TIC, MSI and T(peak) of MR-DCE are valuable in differentiating benign from malignant musculoskeletal tumors. T(peak) has the highest diagnostic specificity, and TIC has the highest diagnostic sensitivity. The mean ADC value are no significant difference between benign and malignant tumors. PMID- 22776600 TI - [Molecular mechanism of hydroxyurea enhances K562 cell apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand]. AB - OBJECTIVE: To explore the molecular mechanism via which the chemotherapeutic drug hydroxyurea (HU) enhances K562 cell apoptosis induced by tumor necrosis factor related apoptosis-inducing ligand (TRAIL). METHODS: Chronic myelogenous leukemia derived K562 and SVT-35 cells were treated with recombinant soluble TRAIL (rsTRAIL) alone or combined with HU for a time course, and the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-4 sulfophenyl-2H-tetrazolium-phenazine methosulphate assay. Western blot was performed to analyze the activation of apoptosis-related protein kinases and the expression of apoptosis inhibitor molecules. RESULTS: The survival rates of SVT 35 and K562 cells treated with 1 MUg/ml rsTRAIL for 24 hours were 32% and 93%, respectively. HU significantly increased the sensitivity of K562 cells to rsTRAIL cytotoxicity. Combination of rsTRAIL and HU resulted in the phosphorylation of rat sarcoma (RAS), mitogen-activated protein kinase/extracellular signal regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), and c Jun N-terminal kinase and in the significant reduction of apoptosis-inhibited molecule Fas associated death domain protein-like interleukin-1 beta-convening enzyme inhibitory protein and cellular inhibitor of apoptosis protein-1 in K562 cells. CONCLUSIONS: HU enhanced K562 cell sensitivity to rsTRAIL is mediated by Ras-MEK-ERK signaling pathway. Expression of antiapoptotic proteins cellular Fas associated death domain protein-like interleukin-1 beta-convening enzyme inhibitory protein and cellular inhibitor of apoptosis protein-1 is also down regulated during this process. These results may through light on the therapeutic study of human chronic myelogenous leukemia. PMID- 22776601 TI - [Clinical and pathological analyses of bevacizumab-induced renal impairment in four patients]. AB - OBJECTIVE: To investigate the clinical and pathological characteristics of bevacizumab-induced renal impairment. METHOD: The clinical and pathological data of 4 patients with bevacizumab-induced renal impairment in Peking Union Medical College Hospital was retrospectively analyzed. RESULTS: There were 2 men and 2 women aged (56.5+/-11.5) years. Before bevacizumab treatment, three non-small cell lung cancer patients (75%) had normal renal function and only one pancreatic cancer patient (25%) had mild renal impairment. After 2-14 cycles of bevacizumab treatment, the most common clinical manifestation of bevacizumab-induced renal injury was proteinuria (>3.5 g/d) (n=4, 100%). Other clinical symptoms included microscopic hematuria (n=2, 50%), malignant hypertension (n=1, 25%), elevated serum creatinine level as accompanied with acute renal failure (n=1, 25%), and anuria (n=1, 25%). Thrombotic microangiopathy was the main pathological type (n=2, 50%), whereas other pathological types included membranoproliferative glomerulonephritis (n=1, 25%) and benign arteriolar nephrosclerosis (n=1, 25%). After the detection of renal impairment, bevacizumab therapy was stopped in all 4 cases (100%). Hemodialysis was performed in the patient with acute renal failure. The prognosis was relatively good. The renal function and proteinuria was completely recovered in one patient (25%), whereas the other three patients (75%) presented with persistent alleviated proteinuria but normal renal function. CONCLUSIONS: Bevacizumab may cause renal injury via complex mechanisms. Therefore, urine protein excretion and renal function should be closely monitored during bevacizumab treatment to identify any renal injury. The prognosis is relatively good after discontinuation of bevacizumab. PMID- 22776602 TI - [Laparoscopic and endoscopic cooperative partial gastrectomy in the treatment of submucosal gastric neoplasms]. AB - OBJECTIVE: To evaluate the feasibility of laparoscopic and endoscopic cooperative partial gastrectomy,a minimally invasive surgery, in treating gastric submucosa lesion. METHODS: We retrospectively analyzed 63 patients [34 women and 29 men, aged (52.8+/-18.1) years (range:14 to 78 years)] who had undergone laparoscopic and endoscopic cooperative partial gastrectomy with preserving cardia and pylorus for gastric submucosal tumor in the past 6 years. All of the patients were followed up for 2-69 months (average 35 months). The clinicopathological data, surgical approaches, and follow-up results were analyzed. RESULTS: The surgery was successfully performed in all these 63 patients, among whom 61 were assisted by endoscopy. The most common symptom was dyspepsia. The mean distance from the lesions locating at fundus or antrum to cardia or pylorus was(2.9+/-1.1)cm. The minimum distance from tumor edge to cardia was 1cm. The diseases included gastrointestinal stromal tumor (n=54), carcinoid tumors (n=3), ectopic pancreas (n=2), lipoma (n=2), and leiomyoma (n=2). The tumor size ranged from 0.8 to 8.2cm, with 44 lesions (69.8%) less than 2cm. Forty-five lesions(71.4%) were located at fundus, 12 (19.0%) at body, and 6 (9.6%) at antrum. No recurrence or death was noted during follow-up. CONCLUSIONS: Laparoscopic and endoscopic cooperative partial gastrectomy is feasible for treating gastric submucosal tumor. Endoscopy is useful for intraoperative localization and supporting, and therefore is especially helpful for preserving cardia and pylorus. PMID- 22776603 TI - [Detection of red fluorescence in the facial skin of healthy individuals and patients with seborrheic dermatitis]. AB - OBJECTIVE: To detect red fluorescence in the facial skin of healthy individuals and patients with seborrheic dermatitis (SD). METHOD: Skin analysis was performed to obtain the ultraviolet images of the facial skins of 61 healthy individuals and 64 SD patients, and the detection rate of red fluorescence was calculated. RESULTS: The detection rate of the red fluorescence was 36.06% in healthy individuals and 70.31% in SD patients (chi(2)=14.728, P<0.005). Additionally, it was significantly higher in T zone, where sebum secretion is high, than in U zone, where sebum secretion is lower (chi(2)=11.529,P<0.05;chi(2)=23.757,P<0.05,respectively). CONCLUSIONS: Red fluorescence exist in both healthy individuals and SD patients, and the detection rate is especially high in the latter. Meanwhile, red fluorescence may be related with sebum secretion. PMID- 22776604 TI - [Toll-like receptor 4: the potential therapeutic target for neuropathic pain]. AB - Activation of microglia plays a vital role in the initiation and maintenance of specific neuropathic pain states. By activating microglia in central nervous system, Toll-like receptor 4 (TLR4) can promote the release of proinflammatory cytokines and neuroactive compounds, participate in the initiation and maintenance of neuropathic pain, and trigger the opiate side effects. Therefore, TLR4 may be a potential therapeutic target for neuropathic pain. Inhibition of TLR4 has shown some biological effects in neuropathic pain models and ibudilast (the TLR4 pathway-inhibiting agent) has been approved for for phase 2 clinical trials. This article briefly reviews the structure, function, and mechanism of TLR4 as well as the development of TLR4-targeted drugs. PMID- 22776605 TI - [Roles of MicroRNAs in cancer stem cells]. AB - Cancer stem cells are cells with stem cell characteristics within a tumor. With increased proliferative capabilities, they are able to self-renew and develop into various cell types, and thus play important roles in the formation, development, metastasis, and recurrence of tumors. MicroRNAs are a class of endogenous, small non-protein coding RNA molecules. Through regulating the expression of genes depending on the complementation between the microRNAs and their targets, microRNAs play important roles in various human cancers. This article summarizes recent research advances in the roles of microRNAs in cancer stem cells. PMID- 22776606 TI - [Research advances in suppressor of cytokine signaling 3]. AB - Suppressor of cytokine signaling(SOCS) 3, a novel type of cytokine signal transduction inhibitory molecules in family of SOCS, is mainly involved in Janus protein tyrosine kinase/signal transducer andantivator of transcription signaling pathway negative feedback regulation. It is involved in inflammation, oxidative stress, cell damage, and apoptosis. Meanwhile, it is closely related to atherosclerosis, obesity, glucose metabolism, insulin resistance, leptin, cancer, asthma, and rheumatic diseases. Therefore, SOCS-3 may become a therapeutic target of these diseases. PMID- 22776607 TI - [Research advances in B-type natriuretic peptide and its clinical application in the patients with cardiovascular diseases]. AB - B-type natriuretic peptide (BNP) is a plasma marker of left ventricular dysfunction and cardiac volume overload. Currently it is mainly used in the cardiovascular field. BNP is an intrinsic regulator of the embryonic stem cell proliferation, and the reduction in BNP can increase the apoptosis rate. The epitope of N terminal pro-brain natriuretic peptide-BNP is most stable. BNP1-32 has the strongest biological activity but with lower plasma level in heart failure patients. The plasma BNP level plays an important role in the diagnosis, prognosis, hospital admission and mortality of heart failure, and can be used as a monitoring indicator in the treatment of heart failure. The deficiency of corin enzyme in patients with heart failure can cause the increase of cracking pro-BNP. BNP can also provide diagnostic and prognostic information for other populations and diseases. Genetic studies on BNP and its receptors also provide important information. Nesiritide, neutral endopeptidase inhibitors, and vasopeptidase inhibitors of the natriuretic peptide synthesis have been used for the treatment of cardiovascular disorders. However, more reliable and accurate approaches for detecting BNP and N terminal pro-brain natriuretic peptide-BNP require further investigations. PMID- 22776608 TI - Role of prophylactic ureteric stents in colorectal surgery. AB - Ureteric injury is a feared complication in colorectal surgery, with a reported incidence of 0.2%-7.6%. Prophylactic ureteric catheter placement has the advantage of facilitating intraoperative ureter identification and assisting in immediate injury recognition and repair. However, its use has been controversial because of fear of ureteric damage during catheter insertion and postoperative urinary complications such as obstructive oliguria and urinary tract infection. Although the exact indications for prophylactic catheter placement are not clearly defined, it is generally used for reoperative cases, large tumors, previous radiation therapy, diverticulitis, fistulas, Crohn's disease and obesity. Herein, we review the incidence and risk factors for ureteric injury, the role of prophylactic ureteric stents and the complications and costs associated with its use in both open and laparoscopic colorectal surgery. PMID- 22776609 TI - Inferior pubic ramus fracture in a child with an associated fracture-haematoma induced inflammatory response. PMID- 22776610 TI - Popliteal vasculature injuries in paediatric trauma patients. AB - Popliteal-artery injuries in the paediatric-trauma patient are uncommon, difficult to diagnose and with prolonged ischaemia lead to substantial complications. We report three cases of popliteal-vasculature injury in paediatric-trauma patients with diverse mechanisms of injury: blunt trauma, penetrating injury and a Salter-Harris I fracture. We present a range of the significant sequelae that can result from paediatric popliteal-artery injury, both physically and psychologically. It is imperative that clinicians have a high index of suspicion when confronted with paediatric patients with trauma around the knee and that popliteal-vasculature injuries are diagnosed early. If insufficiencies are detected, further imaging should be considered, but surgical exploration should not be delayed in the presence of ischaemia. PMID- 22776611 TI - Differential effects of dopaminergic medication on basic motor performance and executive functions in Parkinson's disease. AB - BACKGROUND: Patients with Parkinson's disease (PD) often show deficits in the self-initiation and selection of movements, which can be partly compensated for by external cues. We here investigated impairments in the initiation and selection of self-initiated or externally cued movements in PD. Specifically, we assessed how behavioral changes relate to medication, disease severity, and basic motor or cognitive deficits. METHODS: Seventeen akinetic-rigid PD patients and 16 healthy controls (HC) performed a computerized motor task assessing differences between internally and externally triggered movements and reaction times. Patients performed the task twice in a randomized fashion, once with their regular dopaminergic medication and once 12h after withdrawal of medication. Additionally, all subjects underwent comprehensive neuropsychological and motor assessments. RESULTS: Compared to HC, patients showed a significant slowing across all tasks. Furthermore, patients showed a selective deficit of movement initiation as indexed by longer reaction times when movement lateralization was internally chosen as opposed to being externally cued. This deficit correlated significantly with motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS). Notably, there was no main effect of dopaminergic medication ("ON"/"OFF") on internally and externally triggered movements despite significant improvement of UPDRS and maximum finger tapping frequency in the "ON" state. DISCUSSION: Our results suggest that disease severity in PD patients is related to disturbances in internal action initiation, selection and simple decision processes. Moreover, the data add further support to the notion that dopaminergic medication differentially affects motor and cognitive performance in PD. These findings imply that disturbances in executive functions in PD are also influenced by factors other than reduced dopaminergic activity. PMID- 22776613 TI - Characterization of Er in porous Si. AB - The fabrication of porous Si-based Er-doped light-emitting devices is a very promising developing field for all-silicon light emitters. However, while luminescence of Er-doped porous silicon devices has been demonstrated, very little attention has been devoted to the doping process itself. We have undertaken a detailed study of this process, examining the porous silicon matrix from several points of view during and after the doping. In particular, we have found that the Er-doping process shows a threshold level which, as evidenced by the cross correlation of the various techniques used, does depend on the sample thickness and on the doping parameters. PMID- 22776612 TI - Tensiomyography of selected lower-limb muscles in professional soccer players. AB - Tensiomyography is a non-invasive method of neuromuscular assessment used to measure muscle action characteristics, muscle tone, and muscle fiber type, and provides information on acute and chronic responses of muscle to different training loads. The aims of the present study were: to analyse differences in muscle response and mechanical characteristics of two major muscles of the lower extremity in a large group of Spanish soccer players according to playing position, and to provide group norms against which clinical findings may be compared. Data were collected from 78 professional soccer players (age 26.6 +/- 4.4 years; height: 179.2 +/- 5.3 cm; body mass: 75.8 +/- 5.3 kg). Tensiomyography was recorded from the rectus femoris (RF) and biceps femoris (BF) muscles after 2 days without take part in any strenuous exercise or training. Five tensiomyographic parameters were analyzed: maximal displacement (D(m)), contraction time (T(c)), sustain time (T(s)), delay time (T(d)), and half relaxation time (T(r)). A good to excellent intra-session reliability was found for all contractile parameters (ICC ranged from 0.78 to 0.95). No significant differences between players of any position were observed in absolute values of BF. However, significant differences were observed for T(c), T(r) and T(s) between the different playing positions on RF (P < 0.05, effect size ranged from 1.3 to 1.6). Professional soccer players showed muscles with ability to rapidly generate force during contractions. The neuromuscular profile provided could help in identifying the normative data that are important for the different positions in order to optimize the training and recovery process of each individual player. PMID- 22776614 TI - Protein expression from zooplankton communities in a metal contaminated NW mediterranean coastal ecosystem. AB - Bidimensional and monodimensional polyacrylamide gel electrophoresis were used to study protein expression from zooplankton collected in thirteen stations of Toulon Bay (NW Mediterranean). In this ecosystem, Little Bay showed higher trace metal concentrations (13.5-23.8 nM for Cu, 0.73-1.24 nM for Pb, 27.8-58.7 nM for Zn) than Large Bay (Cu 2.2-15.6 nM; Pb 0.19-0.78 nM; Zn 9.0-38.8 nM). Trace metals positively correlated (p < 0.05) with expression of four zooplankton proteins (MW in kDa/pI: 25.0/5.6; 48.8/4.1; 38.2/4.4; 38.3/5.8) and with biomass of Oithona nana, predominant copepod in Little Bay. Sequencing by LC-MS/MS putatively provided zooplankton identity of these proteins: they were cytoskeleton actin, except one protein that was the chaperone calreticulin. We suggest that actin and calreticulin could be regarded as zooplankton markers of metal stress and be involved in a possible tolerance of O. nana to contamination, contributing to its development in a marine perturbed ecosystem. PMID- 22776615 TI - The effect of monochromatic infrared energy on diabetic wound healing. AB - This study examined the effect of monochromatic infrared energy (MIRE) on diabetic wound healing. Fifteen diabetic rats were given MIRE intervention on their skin wounds located on the dorsum and compared with 15 control diabetic rats. Assessments were conducted for each group at weeks 1, 2 and 4 post wounding (five rats at each time point) by calculating the percentage of wound closures (WCs) and performing histological and immunohistochemical staining on sections of wound tissue. Evaluations of WCs and histological examinations of reepithelialisation, cellular content and granulation tissue formation showed no significant difference between the MIRE and the control group at each time point. Through semi-quantitative immunohistochemical staining, the deposition of type I collagen in the MIRE group was found to have improved when compared with the control group at the end of week 2 (P = 0.05). No significant differences in the myofibroblast population were detected between the two groups. In conclusion, MIRE appeared to promote collagen deposition in the early stage of wound healing in diabetic rats, but the overall wound healing in the MIRE group was not significantly different from that of the control group. PMID- 22776616 TI - A multi-perspective cost-effectiveness analysis comparing rivaroxaban with enoxaparin sodium for thromboprophylaxis after total hip and knee replacement in the German healthcare setting. AB - BACKGROUND: Patients undergoing major orthopaedic surgery (MOS), such as total hip (THR) or total knee replacement (TKR), are at high risk of developing venous thromboembolism (VTE). For thromboembolism prophylaxis, the oral anticoagulant rivaroxaban has recently been included in the German diagnosis related group (DRG) system. However, the cost-effectiveness of rivaroxaban is still unclear from both the German statutory health insurance (SHI) and the German hospital perspective. OBJECTIVES: To assess the cost-effectiveness of rivaroxaban from the German statutory health insurance (SHI) perspective and to analyse financial incentives from the German hospital perspective. METHODS: Based on data from the RECORD trials and German cost data, a decision tree was built. The model was run for two settings (THR and TKR) and two perspectives (SHI and hospital) per setting. RESULTS: Prophylaxis with rivaroxaban reduces VTE events (0.02 events per person treated after TKR; 0.007 after THR) compared with enoxaparin. From the SHI perspective, prophylaxis with rivaroxaban after TKR is cost saving (?27.3 saving per patient treated). However, the cost-effectiveness after THR (?17.8 cost per person) remains unclear because of stochastic uncertainty. From the hospital perspective, for given DRGs, the hospital profit will decrease through the use of rivaroxaban by ?20.6 (TKR) and ?31.8 (THR) per case respectively. CONCLUSIONS: Based on our findings, including rivaroxaban for reimbursement in the German DRG system seems reasonable. Yet, adequate incentives for German hospitals to use rivaroxaban are still lacking. PMID- 22776617 TI - Inhibition of p38 MAPK reduces loss of primary sensory neurons after nerve transection. AB - OBJECTIVE: p38 member of mitogen-activated protein kinase (MAPK) family has been shown to participate in neuropathic pain and axonal regeneration after nerve injury. However, its role in axotomy-induced neuronal apoptosis remains unclear. This study was aimed to examine p38 phosphorylation in the dorsal root ganglia (DRG) and its role in DRG neuronal loss after axotomy. METHODS: Left sciatic nerve transection was performed in all rats. For the temporal study of p38 phosphorylation, the rats were sacrificed at 1 day, 2 weeks, and 2 months after injury. In the second experiment, the rats were divided into control and inhibitor groups receiving vehicle and p38 inhibitor (SB203580, 200 MUg/kg/day intraperitoneally once daily), respectively, for 2 weeks. RESULTS: The p38 phosphorylation was increased in L4/5 DRG at 2 weeks after transection. Immunoreactivity of phospho-p38 was mainly observed in the cytoplasm of small neurons with additional nuclear localization in the axotomized neurons at 2 weeks. SB203580 could reduce the phosphorylation of p38 and its substrate, ATF2, including the upregulation of total caspase-3 expression in the DRG. Moreover, count of L4/5 DRG neurons revealed significantly decreased cell loss in the inhibitor than control groups (17.4% versus 32.5%). CONCLUSION: These data suggest the role of p38 in sensory neuronal loss after nerve transection. Future studies should be done to confirm the apoptotic role of p38 in this condition. PMID- 22776618 TI - Heartworms, macrocyclic lactones, and the specter of resistance to prevention in the United States. AB - In order to provide a background to current concerns relative to the possible resistance of heartworms to macrocyclic lactones, this review summarizes various studies in which lack of efficacies (LOEs) have been observed in dogs on macrocyclic lactone preventives relative to the United States of America. Some of these studies have been published in the peer-reviewed literature, others have appeared in various reports to the Center for Veterinary Medicine (CVM) of the Food and Drug Administration (FDA) of the USA as New Animal Drug Application (NADA) summaries, and one appeared as a letter to US veterinarians. This review also discusses reports relating to the potential problem of heartworm resistance in microfilariae and third-stage larvae, as well as molecular markers associated with resistance to macrocyclic lactones within Dirofilaria immitis. As more work is being done in this area of great concern relative to the protection of dogs from infection using this class of preventives, it seems timely to summarize what is known about heartworms, their potential resistance to treatment, and the means of selecting for resistance genes in populations of this helminth in the laboratory and in the field. PMID- 22776619 TI - Association of an NFKB1 intron SNP (rs4648068) with gastric cancer patients in the Han Chinese population. AB - BACKGROUND: Hyperactivation of nuclear factor-kappaB (NF-kappaB) is associated with various types of tumors. This study investigated the susceptibility of the rs4648068 A/G genotype in the intron region of NFKB1 to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients. METHODS: A hospital-based case-control study of 248 gastric cancer patients and 192 control individuals was conducted in Fudan University Shanghai Cancer Center (Shanghai, China). Single nucleotide polymorphism (SNP) rs4648068 genotype in NFKB1 from blood samples of a total of 440 people was analyzed by polymerase chain reaction-based genotyping. RESULTS: The frequencies of the AA, AG, and GG genotypes of the rs4648068 polymorphism were 31.5%, 47.2%, and 21.3% in the gastric cancer patients and 29.7%, 59.9%, and 10.4% in the control individuals, respectively. We found that the GG genotype was associated with a significantly increased risk of gastric cancer (P = 0.042). Furthermore, among the gastric cancer cases, the rs4648068 GG genotype was associated with high clinical stage (AOR = 2.27, 95% CI: 1.11- 4.66), lymph node involvement (AOR = 2.90, 95% CI = 1.40- 6.03) and serosa invasion (AOR = 2.78, 95% CI = 1.34- 5.75). However, rs4648068 genotypes were not associated with tumor differentiation in gastric cancer patients. CONCLUSIONS: Homozygous rs4648068 GG was associated with an increased risk of gastric cancer, especially for the lymph node status and serosa invasion in Han Chinese population. PMID- 22776621 TI - Sex comparison on long-lasting behavioral and physiological disturbances induced by single shock experience in rats. AB - Enhanced female vulnerability and symptom severity are described in post traumatic stress disorder (PTSD). It remains largely unknown whether females present with more pronounced PTSD-like symptoms than males in rodent models of PTSD. A model of single electric foot-shock followed by situational reminders was used to investigate in rats the impact of sex on potential long-lasting changes in anxiety-like behavior, and in endocrine and physiological responses to stress and fearful situations. Three weeks after single shock exposure (in the dark side of a shuttle box) both male and female rats spent less time in the dark compartment of a dark-light box and in the closed arms of an elevated plus maze than non-shocked controls. Both behaviors were likely due to avoidance of places reminiscent of the initial shock context. The shock exposure had no long-term impact on social interaction behavior or on basal and restraint stress-induced increases in plasma corticosterone. Shock exposure increased sudden silence induced freezing responses and hyperthermia during novelty stress and fear to a similar extent in both males and females and left heart rate responses unaffected. Non-shocked females generally showed a reduced response or faster recovery to baseline under stress- or fearful test conditions as compared to non shocked males, which was likely due to differential sex-specific coping strategies. Taken together, our results suggest that, despite some baseline sex differences, both male and female rats are similarly affected in the long-term by the initial foot-shock exposure used in this particular simulation of PTSD. PMID- 22776622 TI - Individual housing and handling procedures modify anxiety levels of Tg2576 mice assessed in the zero maze test. AB - The zero maze is an unconditioned anxiety test for mice, in which a number of environmental variables can modify the anxiety levels of the animals. In the present study, we have assessed how individual housing, handling procedure and interaction between individual housing and handling procedure affect the baseline anxiety of mice. Thirty-seven wild type mice and eighteen Tg2576 mice were used (obtained from crossing APPSWE hemizygous male C57BL6/SJL background with C57BL6/SJL female). Wild type mice were randomly assigned to four experimental groups: 1) group housed and unhandled, 2) group housed but handled, 3) individually housed, unhandled, and 4) individually housed and handled. In turn, Tg2576 mice were randomly assigned to two experimental groups: 1) individually housed, unhandled, and 2) individually housed and handled. The results show that individually housed mice exhibited more anxiety-related behaviors over a 5 min testing period than the other experimental groups. Use of the handling procedure was associated with a statistically significant reduction in anxiety-related behaviors among individually housed mice. No effects on anxiety-related behavior levels were observed when group housed animals were handled. When activity levels were significantly increased, a new parameter, "Time by Entries", helped to prevent activity from influencing anxiety parameters such as time in the open section of the zero maze test. This knowledge can help to design more efficient experiments without bias from data obtained by means of unconditioned tests. PMID- 22776620 TI - Effects of CB1 and CRF1 receptor antagonists on binge-like eating in rats with limited access to a sweet fat diet: lack of withdrawal-like responses. AB - Positive reinforcement (e.g., appetitive, rewarding properties) has often been hypothesized to maintain excessive intake of palatable foods. Recently, rats receiving intermittent access to high sucrose diets showed binge-like intake with withdrawal-like signs upon cessation of access, suggesting negative reinforcement mechanisms contribute as well. Whether intermittent access to high fat diets also produces withdrawal-like syndromes is controversial. The present study therefore tested the hypothesis that binge-like eating and withdrawal-like anxiety would arise in a novel model of binge eating based on daily 10-min access to a sweet fat diet (35% fat kcal, 31% sucrose kcal). Within 2-3 weeks, female Wistar rats developed binge-like intake comparable to levels seen previously for high sucrose diets (~40% of daily caloric intake within 10 min) plus excess weight gain and adiposity, but absent increased anxiety-like behavior during elevated plus-maze or defensive withdrawal tests after diet withdrawal. Binge-like intake was unaffected by pretreatment with the corticotropin-releasing factor type 1 (CRF(1)) receptor antagonist R121919, and corticosterone responses to restraint stress did not differ between sweet-fat binge rats and chow-fed controls. In contrast, pretreatment with the cannabinoid type 1 (CB(1)) receptor antagonist SR147778 dose-dependently reduced binge-like intake, albeit less effectively than in ad lib chow or sweet fat controls. A priming dose of the sweet fat diet did not precipitate increased anxiety-like behavior, but rather increased plus-maze locomotor activity. The results suggest that CB(1)-dependent positive reinforcement rather than CRF(1)-dependent negative reinforcement mechanisms predominantly maintain excessive intake in this limited access model of sweet-fat diet binges. PMID- 22776623 TI - Translating laboratory discovery to the clinic: from nicotine and mecamylamine to Tourette's, depression, and beyond. AB - The early development of novel nicotinic drugs for Tourette's and depression was a very long journey in discovery, which began with basic behavioral neuroscience studies aimed at understanding how cholinergic and dopaminergic systems interact in the basal ganglia to control goal directed movement. These early rodent studies with nicotine and dopamine antagonists formed the basis for investigating a potentially improved treatment for children suffering from Tourette's syndrome (TS). Clinically, the research trajectory first focused on studies employing the use of nicotine gum to potentiate the therapeutic effect of the dopamine receptor antagonist, haloperidol, in patients with TS. These projects led to the discovery of a new use for a decades-old blood pressure medication, mecamylamine, a nicotine antagonist, which also appeared to provide symptomatic relief in some TS patients when used clinically and was found to reduce symptoms of mood instability and depression. This unexpected discovery led to a new hypothesis regarding the mechanism of action of antidepressants as well as a series of successful independent trials employing mecamylamine, and its active enantiomer, TC5214, as an augmenting agent in the treatment of major depression. This article is a chronological mini review of these basic and clinical translational studies on nicotinic therapeutics for Tourette's syndrome and depression over the past 25 years. PMID- 22776624 TI - Evaluation of smoking on olfactory thresholds of phenyl ethyl alcohol and n butanol. AB - The effect of smoking on the sense of smell remains inconclusive. Previous research suggests that this is due to idiosyncratic acuity dependent on the odorants used in testing. Specifically, it appears that smokers have reduced olfactory acuity to odorants found within cigarettes compared with odorants not within cigarettes. Given that some of these odorants are used in tomography and magnetic resonance imaging, an in-depth understanding of this phenomenon in smoking individuals is crucial. This study assesses the variation of olfactory thresholds in smokers based on selective impairment to two odors commonly used in olfactory testing - n-butanol and phenyl ethyl alcohol (PEA). We presented to 46 participants an 18 step, forced choice, three choice ascending staircase method sniff bottle threshold test using n-butanol and PEA. PEA is present in cigarettes while n-butanol is not. Therefore n-butanol is used as a covariate to control for variance explained by any general olfactory dysfunction. Using this method, we can focus solely on selective impairment. We discovered that n-butanol threshold scores were significantly different between smokers and nonsmokers. In addition, after using n-butanol as covariate, phenyl ethyl alcohol scores remained significantly different between groups. This data suggests that there is an extended impairment to odors within tobacco and this may explain a cause of the inconclusiveness of past research. PMID- 22776625 TI - MSG intake and preference in mice are influenced by prior testing experience. AB - Monosodium glutamate (MSG), the prototypical umami substance, is used as a flavor enhancer in many foods, but when presented alone is often only weakly attractive. Yet with experience mice will develop strong preferences for MSG solution over water. The present experiments explored the conditions that change indifference to preference for MSG. C57BL/6J mice were given a series of 2-day two-bottle tests with water vs. an ascending series of MSG concentrations (0.1-450 mM) to assess preference and intake. Naive mice were indifferent to all concentrations, but following forced one-bottle exposure to 300 mM MSG they preferred most concentrations and consumed more MSG. Exposure to 100mM MSG also increased subsequent MSG preference but not intake. Experience with other nutritive solutions (8% sucrose, 8% Polycose, 8% casein hydrolysate, and isocaloric 3.5% soybean oil emulsion) also enhanced subsequent MSG preference and intake. Polycose and sucrose experience were almost as effective as MSG experience. However, not all sapid solutions were effective; 0.8% sucralose and 10mM MSG exposure did not alter subsequent MSG preference. The generality of the preexposure effect was tested by offering an ascending series (0.1-100 mM) of inosine monophosphate (IMP), another umami substance; initial indifference was converted to preference after forced exposure to 300 mM MSG. Together these results suggest that a combination of oral and post-oral effects may be responsible for the experience effect, with MSG itself the most potent stimulus. A final experiment revealed that MSG preference in naive mice is enhanced by presenting the MSG and water drinking spouts far apart rather than side by side. Thus the preferences for umami solutions in mice are subject to influence from prior tastant experience as well spout position, which should be taken into account when studying acceptance of taste solutions in mice. PMID- 22776626 TI - Photovoltaic properties of PSi impregnated with eumelanin. AB - A bulk heterojunction of porous silicon and eumelanin, where the columnar pores of porous silicon are filled with eumelanin, is proposed as a new organic inorganic hybrid material for photovoltaic applications. The addition of eumelanin, whose absorption in the near infrared region is significantly higher than porous silicon, should greatly enhance the light absorption capabilities of the empty porous silicon matrix, which are very low in the low energy side of the visible spectral range (from about 600 nm downwards). The experimental results show that indeed the photocarrier collection efficiency at longer wavelengths in eumelanin-impregnated samples is clearly higher with respect to empty porous silicon matrices. PMID- 22776627 TI - HElmet therapy Assessment in infants with Deformed Skulls (HEADS): protocol for a randomised controlled trial. AB - BACKGROUND: In The Netherlands, helmet therapy is a commonly used treatment in infants with skull deformation (deformational plagiocephaly or deformational brachycephaly). However, evidence of the effectiveness of this treatment remains lacking. The HEADS study (HElmet therapy Assessment in Deformed Skulls) aims to determine the effects and costs of helmet therapy compared to no helmet therapy in infants with moderate to severe skull deformation. METHODS/DESIGN: Pragmatic randomised controlled trial (RCT) nested in a cohort study. The cohort study included infants with a positional preference and/or skull deformation at two to four months (first assessment). At 5 months of age, all children were assessed again and infants meeting the criteria for helmet therapy were asked to participate in the RCT. Participants were randomly allocated to either helmet therapy or no helmet therapy. Parents of eligible infants that do not agree with enrolment in the RCT were invited to stay enrolled for follow up in a non randomisedrandomised controlled trial (nRCT); they were then free to make the decision to start helmet therapy or not. Follow-up assessments took place at 8, 12 and 24 months of age. The main outcome will be head shape at 24 months that is measured using plagiocephalometry. Secondary outcomes will be satisfaction of parents and professionals with the appearance of the child, parental concerns about the future, anxiety level and satisfaction with the treatment, motor development and quality of life of the infant. Finally, compliance and costs will also be determined. DISCUSSION: HEADS will be the first study presenting data from an RCT on the effectiveness of helmet therapy. Outcomes will be important for affected children and their parents, health care professionals and future treatment policies. Our findings are likely to influence the reimbursement policies of health insurance companies.Besides these health outcomes, we will be able to address several methodological questions, e.g. do participants in an RCT represent the eligible target population and do outcomes of the RCT differ from outcomes found in the nRCT? TRIAL REGISTRATION: ISRCTN18473161. PMID- 22776628 TI - Guess what? Implicit motivation boosts the influence of subliminal information on choice. AB - When is choice affected by subliminal messages? This question has fascinated scientists and lay people alike, but it is only recently that reliable empirical data began to emerge. In the current paper we bridge the literature on implicit motivation and that on subliminal persuasion. We suggest that motivation in general, and implicit motivation more specifically, plays an important role in subliminal persuasion: It sensitizes us to subliminal cues. To examine this hypothesis we developed a new paradigm that allows powerful tests of subliminal influences as well as stringent assessments of subliminality. The results of two experiments suggest that implicit motivation can enhance the effects of subliminal priming on choice. PMID- 22776631 TI - Highlights from the 2012 Schizophrenia International Research Society Conference, April 14-18, 2012. AB - The 2012 Schizophrenia International Research Society (SIRS) Conference, held in Florence, Italy, attracted more than 1,600 attendees from 53 countries to the stately Firenze Fiera Conference Center from April 14-18, 2012. Providing four major plenary sessions, thirty-five symposia sessions and six workshops, this 3rd Biennial SIRS Conference was jointly sponsored by Vanderbilt University School of Medicine, Department of Psychiatry and SIRS. In conjunction with the Schizophrenia Research Forum, a Web project of the Brain and Behavior Research Foundation, and with our thanks to the SIRS organizers and staff, we bring you the following report on the meeting's discussions concerning drug therapy development for schizophrenia, psychological and social treatment for schizophrenia, and the challenges of predicting psychosis with brain imaging. PMID- 22776629 TI - Subcellular targeting of an evolutionarily conserved plant defensin MtDef4.2 determines the outcome of plant-pathogen interaction in transgenic Arabidopsis. AB - The Medicago truncatula gene encoding an evolutionarily conserved antifungal defensin MtDef4.2 was cloned and characterized. In silico expression analysis indicated that MtDef4.2 is expressed in many tissues during the normal growth and development of M. truncatula. MtDef4.2 exhibits potent broad-spectrum antifungal activity against various Fusarium spp. Transgenic Arabidopsis thaliana lines in which MtDef4.2 was targeted to three different subcellular compartments were generated. These lines were tested for resistance to the obligate biotrophic oomycete Hyaloperonospora arabidopsidis Noco2 and the hemibiotrophic fungal pathogen Fusarium graminearum PH-1. MtDef4.2 directed to the extracellular space, but not to the vacuole or retained in the endoplasmic reticulum, conferred robust resistance to H. arabidopsidis. Siliques of transgenic Arabidopsis lines expressing either extracellularly or intracellularly targeted MtDef4.2 displayed low levels of resistance to F. graminearum, but accumulated substantially reduced levels of the mycotoxin deoxynivalenol. The data presented here suggest that extracellularly targeted MtDef4.2 is sufficient to provide strong resistance to the biotrophic oomycete, consistent with the extracellular lifestyle of this pathogen. However, the co-expression of extracellular and intracellular MtDef4.2 is probably required to achieve strong resistance to the hemibiotrophic pathogen F. graminearum which grows extracellularly and intracellularly. PMID- 22776632 TI - One-year treatment continuation in patients prescribed risperidone long-acting injection in New Zealand: a retrospective study. AB - OBJECTIVE: Treatment discontinuation is a major problem in routine clinical settings and is associated with poorer outcomes for conditions like schizophrenia. Risperidone long-acting injection (RLAI) has shown low discontinuation and good tolerability in long-term clinical trials. This retrospective study investigated RLAI continuation in a naturalistic clinical setting in New Zealand. METHODS: Those starting publicly funded RLAI between October 1, 2005 and October 31, 2006 in five public mental health services were included in the study. Data were retrospectively collected for 443 patients 12 months pre- and post-RLAI initiation. Patient demographics, diagnosis, antipsychotic treatment and treatment setting were obtained from clinical files and patient information systems. RESULTS: Patients were mostly male (64%), the mean age was 35.9 years, and were predominantly European (43%) or Maori (29%). Most started RLAI due to adherence issues (77%). Adverse events due to RLAI were reported by 39%; most commonly, extrapyramidal side effects. Fifty-eight percent of patients continued treatment 12 months after starting; patient choice (either refusal or failure to turn up) was the most common reason for discontinuation (54%), followed by lack of efficacy (29%). Alternative antipsychotic treatment was prescribed for 79% of those who discontinued. Regression analysis found continuation was more common for people started in the community, on a compulsory treatment order, with a dose of >25 mg and for non-Maori. CONCLUSIONS: RLAI appears well-tolerated and over half the patients continued treatment for one year or more. Using treatment continuation as an indicator of effectiveness, RLAI appears to be an effective treatment for people with adherence problems in this real world practice setting. PMID- 22776633 TI - Self-esteem and insight as predictors of symptom change in schizophrenia: a longitudinal study. AB - Though it is known that symptom profiles in schizophrenia change throughout the course of the illness, it is not yet clear which psychological antecedents predict these changes. The purpose of the present study was to explore "level of insight into mental illness" and "self-esteem" as predictors of positive symptom change in schizophrenia patients. Fifty-seven schizophrenia patients completed assessments of self-esteem, insight into mental illness, positive symptoms and paranoia once every four weeks for a total of eight individual testing sessions. Hierarchical linear regression analysis revealed that changes in self-esteem predicted future changes in paranoia as well as positive symptoms more broadly; decreases in self-esteem at any given time point were associated with an increase in persecutory beliefs and other positive symptoms at the following assessment. On the other hand, decreases in insight were not significantly associated with paranoia or positive symptoms, either as a stable trait of the mental illness or as a predictor of change over time. Taken together, these results suggest that change in self-esteem, but not insight, has a significant and unique association with positive symptoms of schizophrenia, and may be a valuable target for future treatment. PMID- 22776634 TI - Lurasidone for the acute treatment of adults with schizophrenia: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? AB - OBJECTIVE: To describe the efficacy, safety and tolerability of lurasidone for the acute treatment of schizophrenia using the metrics number needed to treat (NNT) and number needed to harm (NNH). METHODS: Study data were pooled from six Phase II and III, 6-week, randomized, placebo-controlled trials that were conducted to test the efficacy and safety of lurasidone for the acute treatment of schizophrenia. Included were the following interventions: fixed doses of lurasidone 20, 40, 80, 120 and 160 mg/d; haloperidol 10 mg/d; olanzapine 15 mg/d; quetiapine extended-release 600 mg/d; placebo. The following outcomes were assessed: responder rates as defined by a reduction of >=20, 30, 40 or 50% from baseline on the Positive and Negative Syndrome Scale (PANSS) total score; study completion; discontinuation due to an adverse event (AE); weight gain >=7% from baseline; incidence of spontaneously reported AEs; incidence of total cholesterol >=240 mg/dL, low-density lipoprotein cholesterol >=160 mg/dL, fasting triglycerides >=200 mg/dL and glucose >=126 mg/dL at endpoint. NNT for the efficacy outcomes were calculated after excluding one failed study. NNH for the safety/tolerability outcomes were calculated using all six studies. Likelihood of being helped or harmed (LHH) was also calculated to illustrate trade-offs between outcomes of improvement >=30% on the PANSS vs. incidence of akathisia, nausea, sedation, somnolence and parkinsonism. RESULTS: NNT vs. placebo for PANSS reductions >=30% were 6, 6, 7 and 4 for lurasidone doses of 40, 80, 120 and 160 mg/d, respectively, and 4 and 3 for olanzapine 15 mg/d and quetiapine extended release 600 mg/d, respectively. Lurasidone was not associated with any statistically significant disadvantages over placebo for weight gain or metabolic abnormalities; NNH vs. placebo for weight gain >=7% from baseline was 4 for olanzapine and 9 for quetiapine extended-release in contrast to a NNH for this outcome ranging from 43 to 150 for lurasidone 40-160 mg/d. The 5 most consistently encountered adverse events attributable to lurasidone were akathisia, nausea, sedation, somnolence and parkinsonism, with NNH vs. placebo for lurasidone 40-120 mg/d ranging from 6 (akathisia with 120 mg/d) to 30 (parkinsonism with 80 mg/d). Lurasidone 160 mg/d appeared better tolerated than doses of 40, 80 or 120 mg/d for akathisia, nausea, sedation or somnolence, with no NNH values for these adverse events for 160 mg/d vs. placebo being statistically significant. LHH was favorable for lurasidone when contrasting PANSS reductions vs. adverse events. CONCLUSIONS: NNT and NNH can help quantify efficacy, safety and tolerability outcomes and place lurasidone into clinical perspective. Advantages for lurasidone include a low propensity for weight gain and metabolic abnormalities. More commonly encountered adverse events include akathisia, nausea, sedation, somnolence and parkinsonism, but NNH values are generally in the double digits, reflecting an overall tolerable profile. Individual patient characteristics, values and preferences will need to be considered when selecting lurasidone over other antipsychotics. PMID- 22776635 TI - Antipsychotic dosing: extended, and transient. PMID- 22776636 TI - K(+) uptake systems in the yeast Hansenula polymorpha. Transcriptional and post translational mechanisms involved in high-affinity K(+) transporter regulation. AB - We have identified the two main K(+) transporters in the yeast Hansenula polymorpha. So far this is the only yeast with these transporters amenable to molecular genetic analysis. Two ORF-encoding permeases with high similarity to Trk1 and Hak1 are present in the genome of this yeast. Deletion of either of these genes led to defective growth in low K(+). The K(+) and Rb(+) uptake rates showed high affinity of Hak1 for K(+), while the affinity estimated for Trk1 was two orders of magnitude lower. TRK1 was not transcriptionally regulated and HAK1 was strongly induced in response to very low K(+) and down-regulated by the presence of K(+). This process is clearly dependent on calcineurin. The use of a set of strains carrying mutations affecting intracellular protein trafficking revealed that in response to K(+), Hak1 is endocytosed and degraded in the vacuole, this depending on the ubiquitin ligase Rsp5. This is a first insight into the transcriptional and post-translational mechanisms regulating a high affinity K(+) transporter (HAK-type transporter) that allows cells to respond and adapt to K(+) availability. PMID- 22776637 TI - Toward a nonhuman primate model of fetal programming: phenotypic plasticity of the common marmoset fetoplacental complex. AB - Nonhuman primates offer unique opportunities as animal models in the study of developmental programming and the role of the placenta in developmental processes. All primates share fundamental similarities in life history and reproductive biology. Thus, insights gleaned from studies of nonhuman primates have a higher degree of biological salience to human biology than do studies of rodents or agricultural animals. The common marmoset monkey is a small-bodied primate from South America that produces litters of dizygotic fetuses that share a single placental mass. This natural variation allows us to model different intrauterine conditions and associated fetoplacental phenotypes. The marmoset placenta is phenotypically plastic according to litter size. Triplet litters are characterized by low individual fetal weights and significantly more efficient placentas and attendant alterations to the microscopic architecture and endocrine function, thus modeling a nutrient restricted intrauterine environment. Consistent with this model, triplet neonates experience a higher risk of perinatal mortality and an increased likelihood of elevated adult weight. Recent evidence has shown that the intrauterine experience of females has an impact on their own pregnancy outcomes in adulthood: triplet females experience significantly greater pregnancy loss than do twin females. The marmoset monkey thus represents a potential powerful nonhuman primate model of multiple pregnancies, restrictive prenatal experiences, and differential reproductive outcomes in adulthood, which may have important implications for studying the impact of in vitro fertilization on adult reproductive health. It is still too early to determine exactly what developmental pathways lead to this disparity or what specific role the placenta plays; future work on this front will be critical to establish the marmoset as an important model of fetal programming of reproductive function in adulthood and across generations. PMID- 22776638 TI - Membrane transporters in drug development. AB - Membrane transporters have wide, but specific tissue distributions. They can impact on multiple endogenous and xenobiotic processes. Knowledge and awareness within the pharmaceutical industry of their impact on drug absorption, distribution, metabolism and elimination (ADME) and drug safety is growing rapidly. Clinically important transporter-mediated drug-drug interactions (DDIs) have been observed. Up to nine diverse transporters are implicated in the DDIs of a number of widely prescribed drugs, posing a significant challenge to the pharmaceutical industry. There is a complex interplay between multiple transporters and/or enzymes in the ADME and pharmacogenomics of drugs. Integrating these different mechanisms to understand their relative contributions to ADME is a key challenge. Many different factors complicate the study of membrane transporters in drug development. These include a lack of specific substrates and inhibitors, non-standard in vitro tools, and competing/complementary mechanisms (e.g. passive permeability and metabolism). Discovering and contextualizing the contribution of membrane transporters to drug toxicity is a significant new challenge. Drug interactions with key membrane transporters are routinely assessed for central nervous system (CNS) drug discovery therapies, but are not generally considered across the wider drug discovery. But, there is interest in utilizing membrane transporters as drug delivery agents. Computational modeling approaches, notably physiology based/pharmacokinetic (PB/PK) modeling are increasingly applied to transporter interactions, and permit integration of multiple ADME mechanisms. Because of the range of tissues and transporters of interest, robust transporter, in vitro to in vivo, scaling factors are required. Empirical factors have been applied, but absolute protein quantitation will probably be required. PMID- 22776639 TI - The Keap1-Nrf2 cell defense pathway--a promising therapeutic target? AB - By regulating the basal and inducible expression of an abundance of detoxification enzymes, antioxidant proteins, xenobiotic transporters and other stress response proteins, the Keap1-Nrf2 pathway plays a crucial role in determining the sensitivity of mammalian cells to chemical and oxidative insults that have the capacity to provoke cellular harm. This review highlights historical and recent advances in our understanding of the molecular mechanisms that regulate the activity of the Keap1-Nrf2 pathway. The important role of Nrf2 in protecting against the onset of specific diseases and drug-induced toxicities is also examined, alongside the emerging role of Nrf2 in promoting oncogenesis and chemotherapeutic drug resistance. A particular emphasis is placed on the potential for translation of this mechanistic understanding into clinical strategies that can improve human health, with consideration of the potential applications of targeting Nrf2 therapeutically. PMID- 22776640 TI - Animal models of idiosyncratic drug reactions. AB - If we could predict and prevent idiosyncratic drug reactions (IDRs) it would have a profound effect on drug development and therapy. Given our present lack of mechanistic understanding, this goal remains elusive. Hypothesis testing requires valid animal models with characteristics similar to the idiosyncratic reactions that occur in patients. Although it has not been conclusively demonstrated, it appears that almost all IDRs are immune-mediated, and a dominant characteristic is a delay between starting the drug and the onset of the adverse reaction. In contrast, most animal models are acute and therefore involve a different mechanism than idiosyncratic reactions. There are, however, a few animal models such as the nevirapine-induced skin rash in rats that have characteristics very similar to the idiosyncratic reaction that occurs in humans and presumably have a very similar mechanism. These models have allowed testing hypotheses that would be impossible to test in any other way. In addition there are models in which there is a delayed onset of mild hepatic injury that resolves despite continued treatment similar to the "adaptation" reactions that are more common than severe idiosyncratic hepatotoxicity in humans. This probably represents the development of immune tolerance. However, most attempts to develop animal models by stimulating the immune system have been failures. A specific combination of MHC and T cell receptor may be required, but it is likely more complex. Animal studies that determine the requirements for an immune response would provide vital clues about risk factors for IDRs in patients. PMID- 22776641 TI - Genetic polymorphisms affecting drug metabolism: recent advances and clinical aspects. AB - Though current knowledge of pharmacogenetic factors relevant to drug metabolism is fairly comprehensive and this should facilitate translation to the clinic, there are a number of gaps in knowledge. Recent studies using both conventional and novel approaches have added to our knowledge of pharmacogenetics of drug metabolism. Genome-wide association studies have provided new insights into the major contribution of cytochromes P450 to response to therapeutic agents such as coumarin anticoagulants and clopidogrel as well as to caffeine and nicotine. Recent advances in understanding of factors affecting gene expression, both regulation by transcription factors and by microRNA and epigenetic factors, have added to understanding of variation in expression of genes such as CYP3A4 and CYP2E1. The implementation of testing for pharmacogenetic polymorphisms in prescription of selected anticancer drugs and cardiovascular agents is considered in detail, with current controversies and barriers to implementation of pharmacogenetic testing assessed. Though genotyping for thiopurine methyltransferase is now common prior to prescription of thiopurines, genotyping for other pharmacogenetic polymorphisms prior to drug prescription remains uncommon. However, it seems likely that it will become more widespread as both increased evidence that certain pharmacogenetic tests are valuable and cost effective and more accessible genotyping methods become available. PMID- 22776642 TI - Arylamine N-acetyltransferases--from drug metabolism and pharmacogenetics to identification of novel targets for pharmacological intervention. AB - Arylamine N-acetyltransferases (NATs) are defined as xenobiotic metabolizing enzymes, adding an acetyl group from acetyl coenzyme A (CoA) to arylamines and arylhydrazines. NATs are found in organisms from bacteria and fungi to vertebrates. Several isoenzymes, often polymorphic, may be present in one organism. There are two functional polymorphic NATs in humans and polymorphisms in NAT2 underpinned pharmacogenetics as a discipline. NAT enzymes have had a role in important metabolic concepts: the identification of acetyl-CoA and endogenous metabolic roles in bacteria and in eukaryotic folate metabolism. In fungi, NAT is linked to formation of unique metabolites. A broad and exciting canvas of investigations has emerged over the past five years from fundamental studies on NAT enzymes. The role of human NAT1 in breast cancer where it is a biomarker and possible therapeutic target may also underlie NAT's early appearance during mammalian fetal development. Studies of NAT in Mycobacterium tuberculosis have identified potential therapeutic targets for tuberculosis whilst the role of NATs in fungi opens up potential toxicological intervention in agriculture. These developments are possible through the combination of genomics, enzymology and structural data. Strong binding of CoA to Bacillis anthracis NAT may point to divergent roles of NATs amongst organisms as does differential control of mammalian NAT gene expression. The powerful combination of phenotypic investigation following genetic manipulation of NAT genes from mice to mycobacteria has been coupled with generation of isoenzyme-specific inhibitors. This battery of molecular and systems biology approaches heralds a new era for NAT research in pharmacology and toxicology. PMID- 22776643 TI - Human pluripotent stem cells for modeling toxicity. AB - The development of xenobiotics, driven by the demand for therapeutic, domestic and industrial uses continues to grow. However, along with this increasing demand is the risk of xenobiotic-induced toxicity. Currently, safety screening of xenobiotics uses a plethora of animal and in vitro model systems which have over the decades proven useful during compound development and for application in mechanistic studies of xenobiotic-induced toxicity. However, these assessments have proven to be animal-intensive and costly. More importantly, the prevalence of xenobiotic-induced toxicity is still significantly high, causing patient morbidity and mortality, and a costly impediment during drug development. This suggests that the current models for drug safety screening are not reliable in toxicity prediction, and the results not easily translatable to the clinic due to insensitive assays that do not recapitulate fully the complex phenotype of a functional cell type in vivo. Recent advances in the field of stem cell research have potentially allowed for a readily available source of metabolically competent cells for toxicity studies, derived using human pluripotent stem cells harnessed from embryos or reprogrammed from mature somatic cells. Pluripotent stem cell-derived cell types also allow for potential disease modeling in vitro for the purposes of drug toxicology and safety pharmacology, making this model possibly more predictive of drug toxicity compared with existing models. This article will review the advances and challenges of using human pluripotent stem cells for modeling metabolism and toxicity, and offer some perspectives as to where its future may lie. PMID- 22776644 TI - Disposition of biologics. AB - Drug development is a complex process, requiring scientific and regulatory input at almost all stages from multiple groups of expertise. Small molecule development issues are covered in other parts of this volume. This chapter is devoted to discussing the large molecules, or biologics, and the particular nuances involved in developing these molecules as medicines. Our definition of biologic, for the purposes of this chapter, differs from that described by the regulatory bodies. Where regulators state that a biologic is a molecule produced by a living organism, be it a mammalian, insect, yeast or bacteria cell, or whole animal, we prefer to include molecules such as oligonucleotides and peptides here, which are usually chemically synthesized. So our definition is that of a molecule whose composition mostly entails naturally occurring amino acids, sugars or nucleotide bases. There are modifications made chemically to oligonucleotides and peptides to improve their drug-like properties, but for this volume, we class them as biologics. The aim of this chapter is to describe some of the differences, complexities and paradoxically, simplifications in the pharmacokinetics and ADME sciences during drug development of biologics when compared to the more familiar small molecule drug development process. The impact of the particular pharmacokinetics and ADME sciences of biologics on toxicological and pharmacological end points will be discussed. PMID- 22776645 TI - Lack of an association between Paraoxonase 1 gene polymorphisms (Q192R, L55M) and Alzheimer's disease: a meta-analysis. AB - The association between Paraoxonase 1 (PON1) gene polymorphisms (Q192R, L55M) and Alzheimer's disease (AD) risk has been reported inconsistent results. To assess the association between PON1 polymorphisms and AD risk, a meta-analysis was performed. Based on comprehensive searches of the PubMed, Embase, Web of Science, Weipu, and CBM databases, a total of 10 studies including 3081 AD cases and 3054 controls were identified. The pooled odds ratio (OR) with 95% confidence interval (95% CI) were performed. There was no significant association between PON1 Q192R polymorphism and AD risk in all comparison models (R vs. Q, OR=0.89, 95% CI=0.82 0.96; RR vs. QQ, OR=0.83, 95% CI=0.68-1.01; RR+RQ vs. QQ, OR=0.86, 95% CI=0.75 0.97; and RR vs. QR+QQ, OR=0.94, 95% CI=0.81-1.11). For the PON1 L55M polymorphism, lack of an association was also found (L vs. M, OR=0.95, 95% CI=0.86-1.05; LL vs. MM, OR=0.67, 95% CI=0.51-0.88; LL vs. ML+MM, OR=0.82, 95% CI=0.69-0.98; and LL+ML vs. MM, OR=0.75, 95% CI=0.58-0.96). On subgroup analysis by ethnicity, similar results were found. Conclusively, the present meta-analysis revealed that PON1 gene polymorphisms (Q192R, L55M) were unlikely to contribute to AD susceptibility. PMID- 22776647 TI - Permissive role of miR-663 in induction of VEGF and activation of the ATF4 branch of unfolded protein response in endothelial cells by oxidized phospholipids. AB - OBJECTIVE: Atherosclerotic lesions contain high concentrations of oxidized phospholipids (OxPLs) known to induce VEGF via the ATF4 arm of unfolded protein response (UPR), and to promote angiogenic reactions thus potentially contributing to the progression and destabilization of atherosclerotic plaques. In order to get further insights into the mechanisms of cellular stress-induced angiogenesis we studied the role of a specific microRNA (miR-663) in the mechanisms of VEGF induction by OxPLs and inducers of UPR. METHODS: miRNA and mRNA levels were determined using microarray profiling and qRT-PCR methods. Proteins were analyzed by Western blotting. miR-663 levels were changed by transfecting cells with synthetic oligonucleotides. RESULTS: OxPAPC elevated miR-663 in two types of human endothelial cells (ECs). Knockdown of miR-663 inhibited upregulation of VEGF mRNA in ECs treated by OxPAPC, OxPAPS or OxPAPA. In addition, silencing of miR-663 suppressed upregulation by OxPAPC of ATF4 mRNA and protein, as well as a downstream gene TRIB. Similarly to the inhibition of OxPAPC effects, knockdown of miR-663 suppressed elevation of ATF4, VEGF and TRIB in response to another inducer of UPR, tunicamycin. Overexpression of miR-663 reversed the inhibition of VEGF induction by miR-663 inhibitor. CONCLUSION: miR-663 is critically important for 2 key events induced in ECs by stress agents and oxidized lipids, namely induction of transcription factor ATF4 and its downstream gene VEGF. These findings allow hypothesizing that miR-663 plays a general role in control of the ATF4 branch of UPR induced by different agents. PMID- 22776646 TI - A model of nitric oxide induced alpha-synuclein misfolding in Parkinson's disease. AB - Inducible nitric oxide synthase (iNOS) upregulation and consequent NO formation are well-recognized neuroinflammatory responses associated with Parkinson's disease (PD). These contribute to nitrosative protein modifications affecting neuronal injury and cell death. Indeed, a pathobiologic signature for PD is Lewy body formation containing misfolded and aggregated forms of alpha-synuclein (alpha-syn). Moreover, nitration of alpha-syn promotes protein aggregation in disease. To model such pathological events, we constructed controllable iNOS and bicistronic alpha-syn-IRES-tTA adeno-associated virus (AAV) expression vectors. Transduction of iNOS and alpha-syn AAV constructs led to nitration of alpha-syn in neurons and overexpression of iNOS promoted protein aggregation. We posit that this AAV system mimics critical protein misfolding events associated with the pathogenesis of PD. PMID- 22776648 TI - Inhibitory effect of a Ras homologue member I on pancreatic cancer and its modulation on epithelium growth factor receptor-Ras-Raf-mitogen-activated protein kinase/extracellular regulated protein kinase/1/2 pathway. AB - OBJECTIVE: To investigate the regulation of epithelium growth factor receptor (EGFR), pan-Ras, and extracellular regulated protein kinase (ERK) with both a ras homologue member I (ARHI) suppression and epithelium growth factor (EGF) stimulation. METHODS: After identification and implication, the constructed plasmid pIRES2-EGFP-ARHI was transfected into Panc-1. The untransfected cell was also explored as controls. The growth curve was drawn to indicate the proliferation effect of ARHI. EGFR-ELISA was performed to investigate the expression of EGFR. Western blot analysis was used to investigate the expression of protein MAPK/ERK1/2, pan-Ras in Panc-1. RESULTS: The proliferation rate of Panc-1 was inhibited by ARHI compared with both empty plasmid and untransfected cell. The amount of EGFR was parallel in both transfected and untransfected cell but affected by EGF stimulation. The amount of pan-Ras was decreased after ARHI transfection. The optimum concentration of EGF effect on P-ERK was 50 ng/ml. CONCLUSION: Both ARHI and EGF play roles in the EGF-EGFR-Ras-Raf-MAPK/ERK1/2 pathway. PMID- 22776649 TI - Role of microenvironment in the process of expansion of late endothelial progenitor cell in vitro. AB - OBJECTIVE: To study the role of the feeder layer cells as niche in the process of expansion of late endothelial progenitor cell in vitro. METHODS: We cultured mononuclear cells (MNC)from human peripheral blood (PB)on the plate with the feeder layer cells which were irradiated late endothelial progenitor cells(EPC)or human umbilical vein endothelial cells (HUVEC) by EGM-2. After 21 days, the numbers of obtained late EPC colonies were counted separately, and their surface antigen of the late EPC was verified by fluorescence-activated cell sorter (FACS) analysis, and their ability of forming vessel structure with Matrigel in vitro. The differentiation of single stem cell on the feeder layer cell was traced by video-microscopy. RESULTS: After 21 days of culture,(40.0+/-3.9)and(39.3+/ 3.1)late EPC colonies that MNC of a hundred milliliter PB were cultured, respectively, on the feeder layer cells of EPC and HUVEC were much more than (2.0+/-1.3) colonies cultured on without the feeder layer cells (all P <0.05). These cells also expressed CD31,CD34,eNOS,FLt-1,P1H12,Sendo,VE cadherin,and CD117, as shown by FACS analysis. Furthermore, they formed vessel structure with Matrigel in vitro. The video-microscopy showed the asymmetric cell division was participated by the feeder layer cell during the expansion of single stem cell. CONCLUSION: The massive expansion of late EPC can be achieved by the provision of the feeder layer cells, which may be involved in the stem cell asymmetric cell division. PMID- 22776650 TI - Effect of fluid flow-induced shear stress on osteoclast formation induced by osteocyte. AB - OBJECTIVE: To study the role of osteocyte in bone remodeling due to mechanical loading in vitro. METHODS: MLO-Y4 osteocyte-like cells were exposed to fluid flow induced shear stress(12dyn/cm(2))for 0, 1, 2, 4, 6, 12, and 24 hours. Osteocyte exposed to shear stress at different time points were used in co-culture system for 9 days, and then the cells were stained with tartrate-resistant acid phosphatase on the 9(th) day and the amount of positively stained osteoclasts were counted and compared. The expressions of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa (RANKL) were detected by semi-quantitative reverse transcription polymerase chain reaction (semi-quantitative RT-PCR). RESULTS: Compared with bone cells without stimulation with fluid flow-induced shear stress, the amount of osteocytes significantly decreased at all time points after the application of fluid flow-induced shear stress (all P<0.05). The OPG expression at mRNA levels was significantly up-regulated in the first 12 hours (P<0.001), the RANKL mRNA expression was significantly down-regulated in the first 4 hours (P<0.05), and the RANKL/OPG ratio significantly decreased within 12 hours (P<0.01). However, all these indicators showed no significant difference at 24 hours when compared with the pre-stimulation level. CONCLUSION: Osteocytes may act as mechanosensors that are able to inhibit bone resorption after mechanical loading; however, such effect shows certain adaptation ability to shear stress as time goes. PMID- 22776651 TI - Expression of gene associated with retinoid-interferon-induced mortality-19 in preimplantation embryo of mice. AB - OBJECTIVE: To study the expression of gene associated with retinoid-interferon induced mortality-19(GRIM-19) in preimplantation embryo of mice and explore its role in embryonic development. METHODS: The protein and mRNA expressions of GRIM 19 in 2-cell, 4-cell, 8-cell, morula, and blastocyst phases of mice preimplantation embryo were detected by Western blot analysis and Real-time polymerase chain reaction (PCR). RESULTS: GRIM-19 was continuously expressed in every stage of preimplantation embryo of mice. Western blot analysis and Real time PCR demonstrated a gradual increase of GRIM-19 expression from 2-cell, which reached a peak in 8-cell phase and then decreased progressively. CONCLUSIONS: The expression of GRIM-19 in mouse preimplantation embryos changes as at different developmental phases. GRIM-19 may play an important role during embryonic development. PMID- 22776652 TI - Effect of electroconvulsive shock on the glutamate level and the hyperphosphorylation of protein tau in depression rat models whose olfactory bulbs were removed. AB - OBJECTIVE: To explore the effect of the electroconvulsive shock (ECS) on the glutamate level and the hyperphosphorylation of tau protein in depressed rats. METHODS: The depression rat models whose olfactory bulbs were removed were established. Using the analysis of variance of factorial design, we set up two intervention factors including electric current (three levels: 25, 50, and 75 mA) and duration (three levels: 3, 6, and 9 times), which constituted 9 combinations (n=6). Fifty-four adult depression rat models whose olfactory bulbs were removed were randomly divided into nine experimental groups (n=6 in each group). The hippocampus was removed within 12 hours after the ECS finished. The level of glutamate in the hippocampus was detected by high-performance liquid chromatography, and that of Tau protein, which includes p-PHF-1(Ser396/404), p AT8(Ser199/202), and p-12E8(Ser262), in the hippocampus with Western blot analysis. RESULTS: The glutamate level and the hyperphosphorylation of tau protein in the hippocampus of depressed rats remarkably increased. The changes of the hyperphosphorylation of tau protein were correlated with the electric current and duration of ECS, and these two factors showed an synergic effect. CONCLUSION: ECS enhances the hyperphosphorylation of tau protein in the hippocampus of depressed rats by up-regulating the glutamate level. PMID- 22776653 TI - Effects of propofol on brain activation in respond to mechanical stimuli. AB - OBJECTIVE: To observe the effects of different concentrations of propofol on brain regions activated by mechanical stimuli, and then to investigate the analgesic effect of propofol. METHODS: Twenty healthy male volunteers were randomly divided into two groups: light anesthesia group (group L) (BIS 60-80) and deep anesthesia group (group D)(BIS 40-60). Propofol was administrated by target controlled infusion system in pilot study. The target effect site concentration (ESC) of propofol was defined as the average of the ESC from BIS 80 to 60 or BIS 60 to 40 in group L or group D respectively. Mechanical stimuli were applied using von Frey filaments at the center of the left foot, and the pain threshold and VAS scores were evaluated. fMRI examinations were taken 1 week after pilot study with the following sequences: structure imaging+ functional imaging: functional imaging=stimulus sequence+propofol sequence, in which the stimulus sequence was 6 * (20 s on + 20 s off). This sequence was repeated after propofol sequence. RESULTS: As shown by fMRI, in group L, active brain regions of (the second stimulation-the first stimulation, P2-P1) were seen in cingulate gyrus, thalamus, and cerebellum, while active brain regions of (P1-P2) were seen in temporal lobe, frontal gyrus, and occipital lobe. In group D, the active brain region of (P2-P1) was only seen in cerebellum, while active brain regions of (P1 P2) were seen in cingulate gyrus and thalamus. Active brain regions of (deep-low) with propofol infusion in response to vFFs stimulation were observed in cerebellum. CONCLUSIONS: Propofol at different concentrations has different effect on the activation of brain regions. It may exert its analgesic effect via different mechanisms. PMID- 22776654 TI - Clinicopathologic features of gastrointestinal tract involvement of anaplastic large cell lymphoma. AB - OBJECTIVE: To investigate the clinicopathological characteristics of gastrointestinal tract involvement of anaplastic large cell lymphoma (ALCL). METHODS: The clinicopathological features of four patients with ALCL that involved gastrointestinal tract were retrospectively analyzed using immunohistochemical study, T-cell receptor gene rearrangement analysis, and evaluation for Epstein Barr virus infection status. RESULTS: Most tumor cells in all these four cases are large and highly pleomorphic, and all four cases were classified as the common pattern ALCL. Tumor cells in all four tumors expressed CD30, and expressed at least one cytotoxic maker. Two patients were confirmed to be with anaplastic lymphoma kinase (ALK)-positive ALCL, and four patients were negative during in situ hybridization for Epstein-Barr virus-encoded RNA but showed clonal T-cell receptor gene rearrangement. CONCLUSION: Gastrointestinal tract involvement of ALCL has the unique clinicopathological features. PMID- 22776655 TI - Detection of T lymphocyte subsets in the peripheral blood of patients with advanced lung adenocarcinoma. AB - OBJECTIVE: To evaluate the CD4+CD25+ regulatory T cells (Treg) and other lymphocyte subsets in the peripheral blood of patients with advanced lung adenocarcinoma. METHODS: Peripheral blood samples were obtained from 64 patients with advanced lung adenocarcinoma (case group) and analyzed by flow cytometry. The ratios of CD4+CD25+Treg T cells and other T lymphocyte subsets in peripheral blood were compared with those from 33 healthy controls (control group). RESULTS: The percentages of CD3+ and CD3+CD4+ were (66.5+/-11.0)% and (37.7+/-10.6)% respectively in the peripheral blood of the case group, which were significantly lower than those [(72.0+/-6.0)% and (42.0+/-6.4)%] in the control group (t=-3.2, 2.4; P=0.020, 0.015, respectively). The ratio of CD4+ CD25+ Treg cells in case group (10.5+/-4.0)% was significantly higher than that [(8.4+/-3.5)%] in the control group (t=-2.2, P=0.013). CD4+/CD8+ value of case group (1.4+/-0.8) was significantly lower than that (1.8+/-0.7) in control group(t=-2.2, P=0.029). CD3+CD8+, CD8+CD28-, and CD8+CD28+ showed no significant differences (all P>0.05). Smoking, differentiation grade, and size of the tumor showed no association with the function damage of T lymphocyte subsets, while the carcino embryonic antigen level did. CONCLUSIONS: In patients with advanced lung adenocarcinoma, Treg increases and CD4+/CD8+ decreases, suggesting remarkably suppressed immune functions. However, more research is warranted to validate the association of T cells subset dysfunction with smoking, differentiation grade, and size of tumor. PMID- 22776656 TI - Effect of fenofibrate on the secretion of endothelium-derived contracting factors in hypertensive rats. AB - OBJECTIVE: To evaluate the effect of peroxisome proliferator-activated receptor (PPAR)alpha agonist fenofibrate on the secretion of endothelium-derived contracting factors in hypertensive rats. METHODS: The changes of vascular tension in SHR rats after having been incubated with 0.1, 1.0, or 10.0 MUmol/L fenofibrate or 10.0 MUmol/L fenofibrate and PPARalpha antagonist MK866 or PPARgamma antagonist GW9662 for one hour were observed, and the findings were compared with those in WKY rats (control group). The serum levels of vascular endothelial contraction factor prostacyclin (PGF) 1alpha, 2alpha, and thromboxane B2 (TXB2) were determined by enzyme-linked immunosorbent assay (ELISA). The expression of COX-1 protein was determined by Western blot analysis. RESULTS: Compared with the control group, fenofibrate significantly reduced the vasoconstriction ability of the SHR rats(P=0.013). PPARalpha antagonist MK866 significantly improved the vascular contractility of SHR rats that had been incubated with 10.0 MUmol/L fenofibrate (P=0.021). PPARgamma antagonist GW9662 had no significant effect on the vascular contractility of SHR rats after having been incubated with 10.0 MUmol/L fenofibrate (P=0.071). The serum levels of PGF1alpha(P=0.014), 2alpha(P=0.023), and TXB2 (P=0.017) in SHR rats incubated with 10.0 MUmol/L fenofibrate were significantly lower than in the control group. With the presence of vascular endothelium, the expression of COX-1 in SHR rats incubated with fenofibrate was significantly lower than that in SHR rats incubated without fenofibrate (P=0.027). CONCLUSION: Fenofibrate reduces the secretion of endothelium-dependent contracting factors in SHR rats through lowering the expression of COX-1. PMID- 22776657 TI - Identification and expression of a tumor-associated antigen in esophageal squamous cell carcinoma. AB - OBJECTIVE: To search for novel tumor associated antigens (TAA) in esophageal squamous cell carcinoma (ESCC). METHODS: The proteins extracted from tissues of ESCC were separated by two dimensional polyacrylamide gel electrophoresis and transferred to PVDF membrane. Sera from ESCC patients and healthy individuals were used for primary antibodies for Western blot analysis. The differential spots were excised for trypsin hydrolysis and the tryptic peptides were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The identified TAA of ESCC was validated by immunohistochemical staining (IHC). RESULTS: Sera from ESCC patients yielded multiple positive spots, and one 28 800 Da protein that exhibited positive reactivity with 60% (12/20) sera of ESCC patients and only 5% (1/20) sera of healthy controls (P<0.01). The 28 800 Da protein was identified as phosphoglycerate mutase 1 (PGAM1) by MALDI TOF-MS. Immunohistochemical analysis showed that PGAM1 was located in both cytoplasm and nucleus, and had a higher expression in cancer tissues. CONCLUSION: PGAM1 maybe a candidate of ESCC. PMID- 22776658 TI - Marginal and internal fit of two different zirconium copings fabricated on the implant abutment. AB - OBJECTIVE: To evaluate the accuracy of marginal and internal fit of the zirconium copings manufactured by two different computer-aided design(CAD)/computer-aided manufacturing(CAM)system on the implant abutment. METHODS: Using different scanning mode,five Procera((r)) zirconium copings and five Lava zirconium copings were fabricated on the same implant abutment, and then compared with five precious metal copings fabricated by traditional method. Fifteen abutment replica were made with die-stone and the copings were randomly cemented on them, then they were sectioned and invested. The marginal, shoulder, occlusal, and axial fit of each sample was measured by scanning electron microscopy (SEM). RESULTS: There was no significant difference in marginal and axial fit among the three groups(P>0.05). Significant difference in occlusal fit was found among the three groups(P<0.05): Lava group showed better fit than the others(P<0.05)and Procera((r)) group showed better fit than the control(P<0.05). CONCLUSIONS: These two types of zirconium coping have clinically acceptable marginal and internal fit. The internal fit of zirconium coping may be affected by different manufacturing techniques. PMID- 22776659 TI - Correlation of T lymphocyte subsets with blood glucose level and the first-phase insulin secretion in patients with type 2 diabetes mellitus. AB - OBJECTIVE: To explore the relationship between the T cell subsets and glucose level and first-phase insulin secretion function in patients with type 2 diabetes mellitus (T2DM). METHODS: We determined the oral glucose tolerance (OGTT), insulin release test(IRT), body mass index(BMI), glycohemoglobin A1c (HbA1c), T lymphocyte subsets (CD4(+),CD8(+)), and activity of natural kill(NK) cell and ?I(30)/?G(30) in 78 newly diagnosed T2DM patients, 60 impaired glucose tolerance (IGT) patients, and 60 normal controls. RESULTS: DM and IGT patients had significantly lower levels of CD4(+), CD4(+)/CD8(+)ratio, activity of NK cell, and ?I(30)/?G(30) and significantly higher levels of HbA1c and CD8(+)compared with normal controls(all P<0.05). Patients in DM group had significantly lower level of CD4(+),?I(30)/?G(30) and significantly higher levels of FBG and HbA1c compared with IGT group. There was no significant difference in terms of CD8(+), CD4(+)/CD8(+)ratio, and activity of NK cell between IGT and DM groups, whereas CD4(+) T cells were negatively correlated with FBG and HbA1c and positively with ?I(30)/?G(30) . Multiple regression stepwise analysis showed that CD4(+) was independently associated with HbA1c and ?I(30)/?G(30). CONCLUSION: T2DM patients tends to have disorders in cellular immunity, which is correlated with blood glucose level and the insulin secretion function. PMID- 22776660 TI - Time to disappearance of thyroglobulin antibodies and influencing factors in patients with papillary thyroid carcinoma. AB - OBJECTIVE: To investigate the time to disappearance of thyroglobulin antibodies (TgAb) and its influencing factors in papillary thyroid carcinoma (PTC) patients with positive TgAb after radioiodine ((131)I) ablation. METHODS: We retrospectively analyzed the clinical data of 64 PTC patients who had undergone a total thyroidectomy and subsequent (131)I therapy. Patients were divided into two groups according to the presence of concurrent Hashimoto thyroiditis (HD). TgAb1 (TgAb levels determined before (131)I therapy) were above the normal thresholds in all patients. The method of survival analysis (including Life tables and Cox Regression analysis) was used to assess the time to disappearance of TgAb and its influencing factors. RESULTS: The median time to disappearance of positive TgAb (9.0 months vs. 10.4 months, P=0.923) showed no significant difference between these two groups. Cox Regression analysis showed that, among the potential influencing factors including TgAb [partial regression coefficient (B)=-0.004, P=0.001], age(B=-0.018, P=0.362), sex (B=0.644, P=0.320) and HD (B=0.341, P=0.372), only TgAb1 was correlated with the TgAb negative conversion time. CONCLUSIONS: TgAb1 has remarked influence on the time to disappearance of positive TgAb in PTC patients. Patients with a higher TgAb need longer time to achieve negative conversion. PMID- 22776661 TI - Validity of auditory verbal learning test in diagnosis of Alzheimer's disease. AB - OBJECTIVE: To assess the validity of World Health Organization-University of California-Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT) in the diagnosis of Alzheimer's disease (AD). METHODS: Using WHO-UCLA AVLT, we assessed 183 AD patients (AD group),1283 subjects with normal cognitive status (normal control group), and 134 individuals suffered from other diseases easy to be confused with AD (confused control group). RESULTS: The AVLT score was 40.9?0.3 in normal control group, 30.7?0.9 in confused control group, 16.6?1.0 in mild AD group, and 10.2?1.2 in moderate AD group after adjustment for educational level, age, sex, and rural/urban residence (all P<0.05). With the 5th percentage of the overall score as the cutoff point, this tool showed a sensitivity of 86.3% and a specificity of 93.3%. CONCLUSION: WHO-UCLA CVLT is highly sensitive and specific in the diagnosis of AD. PMID- 22776662 TI - Roles of Rho-associated coiled-coil protein kinase in multiple cell behaviors. AB - Rho-associated coiled-coil protein kinase (ROCK) is a serine/threonine kinase that belongs to AGC family of kinases. By inducing the formation of stress fibers and reorganizing the cytoskeleton, it is involved in many biological behaviors of cells including cell contraction, cell migration, cell division, and morphological changes, and thus exerts important roles in regulating the multiple functions of cells. PMID- 22776663 TI - Polycomb group proteins and their roles in regulating stem cell development. AB - Polycomb group (PcG) proteins are a family of epigenetic regulators responsible for the repression of genes in proliferation and differentiation of stem cells. PcG protein complex consists of two important epigenetic regulators: PRC1 (polycomb repressive complex 1) and PRC2 (polycomb repressive complex 2). In order to further understand the functions of PcG proteins in stem cell growth and differentiation, we review the PcG protein composition, PcG protein localization in the target gene, PcG protein recruitment, and the functions of PcG proteins in the development of stem cells. PMID- 22776664 TI - TAR DNA binding protein-43 and fused in sarcoma/translocated in liposarcoma protein in two neurodegenerative diseases. AB - TAR DNA binding protein-43(TDP-43) and fused in sarcoma/translocated in liposarcoma protein (FUS/TLS) have been found to be associated with two neurodegenerative diseases - amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations in TDP-43 and FUS/TLS lead to abnormal protein expressions, which result in altered RNA processing. The pathological changes of TDP-43 and FUS/TLS-associated ALS and FTD are similar. Although the interactions between ALS and FTD remain unknown, it is speculated that TDP-43 and FUS/TLS-associated neurodegenerative diseases may share similar pathogenesis. PMID- 22776665 TI - Molecular biology and clinical features of hereditary non-polyposis colorectal cancer. AB - Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited disease associated with germ-line mutations in mismatch repair genes and microsatellite instability. This article reviews the molecular biology and clinical pathology of HNPCC. PMID- 22776666 TI - Advances in medical treatment of clinically nonfunctioning pituitary adenomas. AB - Clinically nonfunctioning pituitary adenomas are the most common types among pituitary adenomas. These tumors are usually diagnosed in their later stages due to the absence of clinical symptoms and detectable hormonal hypersecretion. Although these tumors are benign, they are hard to be completely removed during neurosurgery due to the massive invasion into the surrounding tissues at diagnosis. Furthermore, relapse is common. In recent years, medical treatment of pituitary adenomas has witnessed a rapid development. New medications have shown certain effectiveness in reducing the tumor size and improving the clinical symptoms. PMID- 22776667 TI - Advances in anti-adhesive materials in preventing pelvic and abdominal post operative adhesions. AB - Post-operative adhesions are a common complication of pelvic and abdominal surgeries. Many approaches for preventing post-operative adhesions have been developed. This review summarizes the recent advances in this topic. PMID- 22776668 TI - Laparoscopic versus open repair for strangulated groin hernias: 188 cases over 4 years. AB - INTRODUCTION: Currently transabdominal pre-peritoneal and totally extraperitoneal repairs are the two standard laparoscopic approaches for groin hernia repair. However, they are still largely reserved for uncomplicated elective cases. To determine whether laparoscopic groin hernia repair can achieve similar results for acute strangulated hernias as laparoscopic cholecystectomy for acute cholecystitis, we analyzed and compared the results of emergency laparoscopic surgery and open repair for strangulated groin hernias performed by our team over the past 4 years. METHODS: This is a retrospective analysis of prospectively collected data. We analyzed the results of patients admitted between January 2007 and January 2011 who were diagnosed with acute strangulated groin hernia and underwent emergency open or laparoscopic hernia repair during the same admission. Patients' demographic details, mode of presentation, type of hernia, intraoperative findings, operative time, postoperative course and complications were compared. RESULTS: In total, 188 patients fulfilled the criteria for emergency surgical repair of strangulated groin hernias; 57 received laparoscopic and 131 received open repairs. The mean operative time was 79.82 +/- 29.571 min and 80.75 +/- 35.161 min, respectively. More laparotomies were performed in the open group (19 vs 0). The wound infection rate was significantly higher in the open group (12 vs 0). The mean hospital stay was shorter in the laparoscopic group (4.39 days vs 7.34 days). There was no mesh infection in either group. Recurrence occurred one case in the laparoscopic group and in three cases in the open group. CONCLUSIONS: Emergency laparoscopic repair for strangulated groin hernias is feasible and appears to have a lower morbidity relative to open repair. Further study should be performed to evaluate its full potential. PMID- 22776669 TI - The total release of xenon-133 from the Fukushima Dai-ichi nuclear power plant accident. AB - The accident at the Fukushima Dai-ichi nuclear power plant (FD-NPP) on 11 March 2011 released large amounts of radioactivity into the atmosphere. We determine the total emission of the noble gas xenon-133 ((133)Xe) using global atmospheric concentration measurements. For estimating the emissions, we used three different methods: (i) using a purely observation-based multi-box model, (ii) comparisons of dispersion model results driven with GFS meteorological data with the observation data, and (iii) such comparisons with the dispersion model driven by ECMWF data. From these three methods, we have obtained total (133)Xe releases from FD-NPP of (i) 16.7 +/- 1.9 EBq, (ii) 14.2 +/- 0.8 EBq, and (iii) 19.0 +/- 3.4 EBq, respectively. These values are substantially larger than the entire (133)Xe inventory of FD-NPP of about 12.2 EBq derived from calculations of nuclear fuel burn-up. Complete release of the entire (133)Xe inventory of FD-NPP and additional release of (133)Xe due to the decay of iodine-133 ((133)I), which can add another 2 EBq to the (133)Xe FD-NPP inventory, is required to explain the atmospheric observations. Two of our three methods indicate even higher emissions, but this may not be a robust finding given the differences between our estimates. PMID- 22776671 TI - Reproductive skew can provide a net advantage in both conditional and unconditional social interactions. AB - We revisit a model for the evolution of costly social behaviour in the presence of reproductive skew. The model population is structured into groups, and reproductive skew is captured by assuming individuals adopt one of two social roles (dominant/subordinate). Unlike previous work, we adopt an ultimate perspective by tracking a mutant allele over the entire course of an invasion. Our main analysis applies the theory of branching processes, but a parallel analysis using the inclusive-fitness approach is also provided. Our first two results are modifications of known inequalities describing selective advantages for behaviours expressed conditional upon social status. We find that altruistic subordinate individuals are favoured more readily than previously thought; spiteful dominant individuals, however, are favoured less readily. Secondly, we identify the condition under which unconditional altruism (performed by both dominant and subordinate) will be adaptive. Our third main result shows that increasing the strength of selection can also change the range of parameters over which costly social behaviours are favoured. We find that stronger selection makes it relatively easier for subordinate altruism to emerge, but more difficult for dominant spite and unconditional altruism to occur. We discuss the possible implications of our results for human social evolution. PMID- 22776670 TI - Development of a community-based model for respiratory care services. AB - BACKGROUND: Chronic respiratory diseases are a major cause of mortality and morbidity, and represent a high chronic disease burden, which is expected to rise between now and 2020. Care for chronic diseases is increasingly located in community settings for reasons of efficiency and patient preference, though what services should be offered and where is contested. Our aim was to identify the key characteristics of a community-based service for chronic respiratory disease to help inform NHS commissioning decisions. METHODS: We used the Delphi method of consensus development. We derived components from Wagner's Chronic Care Model (CCM), an evidence-based, multi-dimensional framework for improving chronic illness care. We used the linked Assessment of Chronic Illness Care to derive standards for each component.We established a purposeful panel of experts to form the Delphi group. This was multidisciplinary and included national and international experts in the field, as well as local health professionals involved in the delivery of respiratory services. Consensus was defined in terms of medians and means. Participants were able to propose new components in round one. RESULTS: Twenty-one experts were invited to participate, and 18 agreed to take part (85.7% response). Sixteen responded to the first round (88.9%), 14 to the second round (77.8%) and 13 to the third round (72.2%). The panel rated twelve of the original fifteen components of the CCM to be a high priority for community-based respiratory care model, with varying levels of consensus. Where consensus was achieved, there was agreement that the component should be delivered to an advanced standard. Four additional components were identified, all of which would be categorised as part of delivery system design. CONCLUSIONS: This consensus development process confirmed the validity of the CCM as a basis for a community-based respiratory care service and identified a small number of additional components. Our approach has the potential to be applied to service redesign for other chronic conditions. PMID- 22776672 TI - Presence of thoracic duct abnormalities in patients with primary lymphoedema of the extremities. AB - OBJECTIVES: Primary lymphoedema is said to be caused by lymph duct malformations, lymphatic hypoplasia or lymphatic agenesis, but no definite treatment has been established. In this study, we used magnetic resonance thoracic ductography (MRTD) to assess the morphology of the thoracic duct in patients with primary lymphoedema. METHODS: The study was conducted on nine patients with primary lymphoedema who were hospitalised at the Department of Plastic and Reconstructive Surgery (University of Tokyo Hospital) from September 2007 through April 2011. RESULTS: The patients consisted of five men and four women, aged 20-54 years (mean age: 31.1 years). Five of them were in early-onset group and the rest were in late-onset group. In the 6 months prior to the onset of oedema, three of the four patients in the late-onset group had episodes of trauma near the areas which would later be affected by lymphoedema. MRTD showed no clear image of the thoracic duct in four of five patients in the early-onset group. CONCLUSIONS: MRTD assessment of patients diagnosed as 'primary lymphoedema' indicates that the pathogenetic mechanisms seen in late-onset patients are completely different from those found in early-onset patients, and may be classified as 'traumatic lymphoedema.' PMID- 22776673 TI - The Newcastle flip operation for bilateral cleft lip muscle repair. AB - Repair of bilateral cleft lip is a challenging operation as the prolabium and premaxilla can be very protrusive. We present a simple one stage technique allowing functional repair of bilateral cleft lip. PMID- 22776674 TI - Making an impact: the Journal of Foot and Ankle Research. PMID- 22776675 TI - Diffusion properties of molecules at the blood-brain interface: potential contributions of astrocyte endfeet to diffusion barrier functions. AB - Molecular diffusion in the extracellular space (ECS) plays a key role in determining tissue physiology and pharmacology. The blood-brain barrier regulates the exchange of substances between the brain and the blood, but the diffusion properties of molecules at this blood-brain interface, particularly around the astrocyte endfeet, are poorly characterized. In this study, we used 2-photon microscopy and acute brain slices of mouse neocortex and directly assessed the diffusion patterns of fluorescent molecules. By observing the diffusion of unconjugated and 10-kDa dextran-conjugated Alexa Fluor 488 from the ECS of the brain parenchyma to the blood vessels, we find various degrees of diffusion barriers at the endfeet: Some allow the invasion of dye inside the endfoot network while others completely block it. Detailed analyses of the time course for dye clearance support the existence of a tight endfoot network capable of acting as a diffusion barrier. Finally, we show that this diffusion pattern collapses under pathological conditions. These data demonstrate the heterogeneous nature of molecular diffusion dynamics around the endfeet and suggest that these structures can serve as the diffusion barrier. Therefore, astrocyte endfeet may add another layer of regulation to the exchange of molecules between blood vessels and brain parenchyma. PMID- 22776676 TI - Complex epileptic palilalia: a case report. AB - Palilalia is a kind of motor perseveration involving speech, consisting in the continuous repetition of words or phrases, or both. Rarely it occurs in seizure disorders as ictal or post-ictal manifestation. We report a case of epileptic palilalia in a 71-year-old patient with a previous history of intracerebral haemorrhage in the left frontal region, characterized by the continuous repetition of the same speech sequence for few minutes. EEG recordings during NREM sleep and wakefulness showed recurrent and prolonged focal subclinical epileptiform paroxysms in the left mesial frontal region. Our case confirms the role of the left frontal lobe, reliably of the supplementary motor area (SMA), as neuroanatomic origin of ictal palilalia. PMID- 22776677 TI - Severity of anxiety and depression are related to a higher perception of adverse effects of antiepileptic drugs. AB - After reviewing the negative effects of antiepileptic drugs (AEDs) on general health and quality of life, the Commission on Outcome Measurement from the International League Against Epilepsy (ILAE) recommended incorporating reliable and valid tools in clinical essays in order to achieve a more accurate assessment of the subjective adverse effects rate and disease severity when using AEDs. PURPOSE: The aim of this study was to correlate the severity of adverse effects of AEDs, with the presence of anxiety and depression in patients with epilepsy. METHODS: The Spanish version of the Liverpool Adverse Events Profile (LAEP) and the hospital anxiety and depression scale (HADS) were applied on 130 consecutive outpatients with epilepsy from the epilepsy clinic at the Mexico's National Institute of Neurology and Neurosurgery. A correlation analysis was carried out to determine if the presence of depression and anxiety was related to the adverse effects of AEDs. The relation between LAEP scores with other epidemiological variables was also assessed. RESULTS: Our study found a positive correlation between the LAEP and the HADS scores (p < or = 0.01). The most common adverse effects were drowsiness (81.5% [n=106]), difficulty in concentrating (76% [n=99]), and nervousness and/or agitation (75% [n=97]). Female gender, a history of febrile seizures, persistent seizures and polytherapy were associated with a higher toxicity on LAEP. In our study, age at epilepsy onset, duration of epilepsy, type of epilepsy and patients' age were not related to higher LAEP scores. CONCLUSION: Adverse effects to AEDs can be related with the presence of psychiatric disorders such as anxiety and depression in patients with epilepsy. PMID- 22776678 TI - Occupational lead exposure among automotive garage workers - a case study for Jimma town, Ethiopia. AB - BACKGROUND: In Ethiopia, although there are numerous small-scale and medium industries which use lead-based raw materials that may pose health risks to workers, there are no workplace regulations for lead exposure. Moreover, there are no studies carried out on the blood lead levels (BLLs) of workers or on the contribution of common workplace practices to lead poisoning. METHOD: A cross sectional study on the BLLs of 45 automotive garage workers and 40 non-garage workers was carried out in the town of Jimma, Ethiopia. In addition to BLL analysis, data on some risk factors such as smoking, and chewing 'khat' (the leaves of Catha adulis) were gathered through structured questionnaires and interviews and data analysis was performed using SPSS (version 16). The t-test was used to compare mean BLLs of study groups. The analysis of variance (ANOVA), Kruskal-Wallis, Pearson chi-square and odds ratio tests were used to investigate the associations between specific job type, smoking and/or 'khat' chewing, service years and occurrence of non-specific symptoms with BLLs. RESULTS: The mean BLL of the automotive-garage workers was found to be significantly greater than that of the controls. The BLLs of all the lead-exposed individuals were found to be over 10 MUg/dL, and 53% of them had BLLs ranging 12 - 20 MUg/dL, with the remaining 47% having over 20 MUg/dL. The BLL of the workers increased with the duration of working in an automotive garage.Individuals involved in manual car painting comprise a larger percentage (58%) of those with the highest BLLs (>= 20 MUg/dL). Lead accumulation in individuals who chew 'khat' in the work place was found to be faster than in those who are not used to chewing 'khat'. 'Khat' is an evergreen shrub native to tropical East Africa, with dark green opposite leaves which are chewed when fresh for their stimulating effects. CONCLUSION: The findings of the study have clearly demonstrated that the BLLs of automotive-garage workers in Jimma town are considerably high with a range of 11.73 - 36.52 MUg/dL and the workers are in danger of impending lead toxicity. The BLLs of the workers are influenced by their occupational practices, chewing Catha adulis leaves at the workplace, and the time spent working in an automotive garage. PMID- 22776679 TI - The Longitudinal Urban Cohort Ageing Study (LUCAS): study protocol and participation in the first decade. AB - BACKGROUND: We present concept, study protocol and selected baseline data of the Longitudinal Urban Cohort Ageing Study (LUCAS) in Germany. LUCAS is a long running cohort study of community-dwelling seniors complemented by specific studies of geriatric patients or diseases. Aims were to (1) Describe individual ageing trajectories in a metropolitan setting, documenting changes in functional status, the onset of frailty, disability and need of care; (2) Find determinants of healthy ageing; (3) Assess long-term effects of specific health promotion interventions; (4) Produce results for health care planning for fit, pre-frail, frail and disabled elderly persons; (5) Set up a framework for embedded studies to investigate various hypotheses in specific subgroups of elderly. METHODS/DESIGN: In 2000, twenty-one general practitioners (GPs) were recruited in the Hamburg metropolitan area; they generated lists of all their patients 60 years and older. Persons not terminally ill, without daily need of assistance or professional care were eligible. Of these, n = 3,326 (48 %) agreed to participate and completed a small (baseline) and an extensive health questionnaire (wave 1). In 2007/2008, a re-recruitment took place including 2,012 participants: 743 men, 1,269 women (647 deaths, 197 losses, 470 declined further participation). In 2009/2010 n = 1,627 returned the questionnaire (90 deaths, 47 losses, 248 declined further participation) resulting in a good participation rate over ten years with limited and quantified dropouts. Presently, follow-up data from 2007/2008 (wave 2) and 2009/2010 (wave 3) are available. Data wave 4 is due in 2011/2012, and the project will be continued until 2013. Information on survival and need of nursing care was collected continuously and cross-checked against official records. We used Fisher's exact test and t-tests. The study served repeatedly to evaluate health promotion interventions and concepts. DISCUSSION: LUCAS shows that a cohort study of older persons is feasible and can maintain a good participation rate over ten years, even when extensive self-reported health data are collected repeatedly through self-filled questionnaires. Evidently individual health developments of elderly persons can be tracked quantifying simultaneously behaviour, co-morbidity, functional competence and their changes. In future, we expect to generate results of significance about the five study aims listed above. PMID- 22776681 TI - Visiting Caribbean bioethicists. PMID- 22776680 TI - Ca(2+) influx and neurotransmitter release at ribbon synapses. AB - Ca(2+) influx through voltage-gated Ca(2+) channels triggers the release of neurotransmitters at presynaptic terminals. Some sensory receptor cells in the peripheral auditory and visual systems have specialized synapses that express an electron-dense organelle called a synaptic ribbon. Like conventional synapses, ribbon synapses exhibit SNARE-mediated exocytosis, clathrin-mediated endocytosis, and short-term plasticity. However, unlike non-ribbon synapses, voltage-gated L type Ca(2+) channel opening at ribbon synapses triggers a form of multiquantal release that can be highly synchronous. Furthermore, ribbon synapses appear to be specialized for fast and high throughput exocytosis controlled by graded membrane potential changes. Here we will discuss some of the basic aspects of synaptic transmission at different types of ribbon synapses, and we will emphasize recent evidence that auditory and retinal ribbon synapses have marked differences. This will lead us to suggest that ribbon synapses are specialized for particular operating ranges and frequencies of stimulation. We propose that different types of ribbon synapses transfer diverse rates of sensory information by expressing a particular repertoire of critical components, and by placing them at precise and strategic locations, so that a continuous supply of primed vesicles and Ca(2+) influx leads to fast, accurate, and ongoing exocytosis. PMID- 22776683 TI - A novel DCAF1-binding motif required for Vpx-mediated degradation of nuclear SAMHD1 and Vpr-induced G2 arrest. AB - HIV-2 and closely related SIV Vpx proteins are essential for viral replication in macrophages and dendritic cells. Vpx hijacks DCAF1-DDB1-Cul4 E3 ubiquitin ligase to promote viral replication. DCAF1 is essential for cell proliferation and embryonic development and is responsible for the polyubiquitination of poorly defined cellular proteins. How substrate receptors recruit the DCAF1-containing E3 ubiquitin ligase to induce protein degradation is still poorly understood. Here we identify a highly conserved motif (Wx4Phix2Phix3APhixH) that is present in diverse Vpx and Vpr proteins of primate lentiviruses. We demonstrate that the Wx4Phix2Phix3APhixH motif in SIVmac Vpx is required for both the Vpx-DCAF1 interaction and/or Vpx-mediated degradation of SAMHD1. DCAF1-binding defective Vpx mutants also have impaired ability to promote SIVDeltaVpx virus infection of myeloid cells. Critical amino acids in the Wx4Phix2Phix3APhixH motif of SIV Vpx that are important for DCAF1 interaction maintained the ability to bind SAMHD1, indicating that the DCAF1 and SAMHD1 interactions involve distinctive interfaces in Vpx. Surprisingly, VpxW24A mutant proteins that were still capable of binding DCAF1 and SAMHD1 lost the ability to induce SAMHD1 degradation, suggesting that Vpx is not a simple linker between the DCAF1-DDB1-Cul4 E3 ubiquitin ligase and its substrate, SAMHD1.VpxW24A maintained the ability to accumulate in the nucleus despite the fact that nuclear, but not cytoplasmic, mutant forms of SAMHD1 were more sensitive to Vpx-mediated degradation. The Wx4Phix2Phix3APhixH motif in HIV 1 Vpr is also required for the Vpr-DCAF1 interaction and Vpr-induced G2 cell cycle arrest. Thus, our data reveal previously unrecognized functional interactions involved in the assembly of virally hijacked DCAF1-DDB1-based E3 ubiquitin ligase complex. PMID- 22776682 TI - Impact of community-based support services on antiretroviral treatment programme delivery and outcomes in resource-limited countries: a synthetic review. AB - BACKGROUND: Task-shifting to lay community health providers is increasingly suggested as a potential strategy to overcome the barriers to sustainable antiretroviral treatment (ART) scale-up in high-HIV-prevalence, resource-limited settings. The dearth of systematic scientific evidence on the contributory role and function of these forms of community mobilisation has rendered a formal evaluation of the published results of existing community support programmes a research priority. METHODS: We reviewed the relevant published work for the period from November 2003 to December 2011 in accordance with the guidelines for a synthetic review. ISI Web of Knowledge, Science Direct, BioMed Central, OVID Medline, PubMed, Social Services Abstracts, and Sociological Abstracts and a number of relevant websites were searched. RESULTS: The reviewed literature reported an unambiguous positive impact of community support on a wide range of aspects, including access, coverage, adherence, virological and immunological outcomes, patient retention and survival. Looking at the mechanisms through which community support can impact ART programmes, the review indicates that community support initiatives are a promising strategy to address five often cited challenges to ART scale-up, namely (1) the lack of integration of ART services into the general health system; (2) the growing need for comprehensive care, (3) patient empowerment, (4) and defaulter tracing; and (5) the crippling shortage in human resources for health. The literature indicates that by linking HIV/AIDS care to other primary health care programmes, by providing psychosocial care in addition to the technical-medical care from nurses and doctors, by empowering patients towards self-management and by tracing defaulters, well-organised community support initiatives are a vital part of any sustainable public-sector ART programme. CONCLUSIONS: The review demonstrates that community support initiatives are a potentially effective strategy to address the growing shortage of health workers, and to broaden care to accommodate the needs associated with chronic HIV/AIDS. The existing evidence suggests that community support programmes, although not necessarily cheap or easy, remain a good investment to improve coverage of communities with much needed health services, such as ART. For this reason, health policy makers, managers, and providers must acknowledge and strengthen the role of community support in the fight against HIV/AIDS. PMID- 22776684 TI - Efficacy and safety of bipolar electrode grasping forceps for laparoscopic myomectomy in uterine cervical myoma. AB - INTRODUCTION: Myomectomy for cervical myoma is problematic because cervical myomas are very close to neighboring structures, such as the ureters, uterine artery, bladder and rectum. There are a few reports on laparoscopic myomectomy for cervical myomas to avoid blood loss, such as occlusion of iliac arteries and clipping of the uterine artery. We evaluated the efficacy and safety of bipolar electrode grasping forceps for laparoscopic myomectomy in uterine cervical myoma. METHODS: From November 2006 to May 2009, eight women with uterine cervical myoma underwent laparoscopic myomectomy. We employed electrode grasping forceps with a combination of two tenaculums for separating and securing hemostatsis. RESULTS: Seven of eight cases were successfully treated by laparoscopic myomectomy, but one patient, with a large 900-g myoma was converted to the laparotomy as a result of blood loss (1800 mL). Among the other seven cases, the average weight of the myoma was 132 g (range, 16-310 g) and the operating time was 176 min. (range, 125 255 min). No complications occurred. Of the four cases who wanted to become pregnant postoperatively, two became pregnant and delivered by Caesarean section. CONCLUSION: These findings indicate that bipolar electrode grasping forceps using two tenaculums for traction of the myoma are useful for laparoscopic myomectomy in cervical myomas. PMID- 22776685 TI - Phase-dependent changes in local dynamic stability of human gait. AB - Several methods derived from nonlinear time series analysis have been suggested to quantify stability in human gait kinematics. One of these methods is the definition of the maximum finite time Lyapunov exponent (lambda) that quantifies how the system responds to infinitesimal perturbations. However, there are fundamental limitations to the conventional definition of lambda for gait kinematics. First, exponential increase in initial perturbations cannot be assumed since real-life perturbations of gait kinematics are finite sized. Second, the transitions between single and double support phase within each stride cycle define two distinct dynamical regimes that may not be captured by a single lambda. The present article presents a new method to quantify intra-stride changes lambda(t) in local dynamical stability and employs the method to 3D lower extremity gait kinematics in 10 healthy adults walking on a treadmill at 3 different speeds. All participants showed an intra-stride change in lambda(t) in the transition between single and double support phase. The intra-stride change reflected an both a increase and decrease in lambda(t) at heel strike and toe off, respectively, with increased gait speed. Furthermore, a close relationship was found between the intra-stride change in standard deviation of foot velocity in the anterior-posterior direction and the intra-stride change of the initial perturbations. The present results indicate that local dynamical stability has gait phase-dependent changes that are not identified by conventional computation of a single lambda. PMID- 22776686 TI - Spatial distribution of tissue level properties in a human femoral cortical bone. AB - The mechanical properties of cortical bone are determined by a combination bone tissue composition, and structure at several hierarchical length scales. In this study the spatial distribution of tissue level properties within a human femoral shaft has been investigated. Cylindrically shaped samples (diameter: 4.4mm, N=56) were prepared from cortical regions along the entire length (20-85% of the total femur length), and around the periphery (anterior, medial, posterior and lateral quadrants). The samples were analyzed using scanning acoustic microscopy (SAM) at 50MHz and synchrotron radiation micro computed tomography (SRMUCT). For all samples the average cortical porosity (Ct.Po), tissue elastic coefficients (c(ij)) and the average tissue degree of mineralization (DMB) were determined. The smallest coefficient of variation was observed for DMB (1.8%), followed by BV/TV (5.4%), c(ij) (8.2-45.5%), and Ct.Po (47.5%). Different variations with respect to the anatomical position were found for DMB, Ct.Po and c(ij). These data address the anatomical variations in anisotropic elastic properties and link them to tissue mineralization and porosity, which are important input parameters for numerical multi-scale bone models. PMID- 22776687 TI - A new bi-axial cantilever beam design for biomechanics force measurements. AB - The demand for measuring forces exerted by animals during locomotion has increased dramatically as biomechanists strive to understand and implement biomechanical control strategies. In particular, multi-axial force transducers are often required to capture animal limb coordination patterns. Most existing force transducers employ strain gages arranged in a Wheatstone bridge on a cantilever beam. Bi-axial measurements require duplicating this arrangement in the transverse direction. In this paper, we reveal a method to embed a Wheatstone bridge inside another to allow bi-axial measurements without additional strain gages or additional second beams. This hybrid configuration resolves two force components from a single bridge circuit and simplifies fabrication for the simultaneous assessment of normal and transverse loads. This design can be implemented with two-dimensional fabrication techniques and can even be used to modify a common full bridge cantilever force transducer. As a demonstration of the new design, we built a simple beam which achieved bi-axial sensing capability that outperformed a conventional half-bridge-per-axis bi-axial strain gage design. We have used this design to measure the ground reaction forces of a crawling caterpillar and a caterpillar-mimicking soft robot. The simplicity and increased sensitivity of this method could facilitate bi-axial force measurements for experimental biologists. PMID- 22776688 TI - Characterizing local collagen fiber re-alignment and crimp behavior throughout mechanical testing in a mature mouse supraspinatus tendon model. AB - BACKGROUND: Collagen fiber re-alignment and uncrimping are two postulated mechanisms of tendon structural response to load. Recent studies have examined structural changes in response to mechanical testing in a postnatal development mouse supraspinatus tendon model (SST), however, those changes in the mature mouse have not been characterized. The objective of this study was to characterize collagen fiber re-alignment and crimp behavior throughout mechanical testing in a mature mouse SST. METHOD OF APPROACH: A tensile mechanical testing set-up integrated with a polarized light system was utilized for alignment and mechanical analysis. Local collagen fiber crimp frequency was quantified immediately following the designated loading protocol using a traditional tensile set up and a flash-freezing method. The effect of number of preconditioning cycles on collagen fiber re-alignment, crimp frequency and mechanical properties in midsubstance and insertion site locations were examined. RESULTS: Decreases in collagen fiber crimp frequency were identified at the toe-region of the mechanical test at both locations. The insertion site re-aligned throughout the entire test, while the midsubstance re-aligned during preconditioning and the test's linear-region. The insertion site demonstrated a more disorganized collagen fiber distribution, lower mechanical properties and a higher cross sectional area compared to the midsubstance location. CONCLUSIONS: Local collagen fiber re-alignment, crimp behavior and mechanical properties were characterized in a mature mouse SST model. The insertion site and midsubstance respond differently to mechanical load and have different mechanisms of structural response. Additionally, results support that collagen fiber crimp is a physiologic phenomenon that may explain the mechanical test toe-region. PMID- 22776689 TI - Sexual dimorphism in human browridge volume measured from 3D models of dry crania: a new digital morphometrics approach. AB - Sex estimation from the human skull is often a necessary step when constructing a biological profile from unidentified human remains. Traditional methods for determining the sex of a skull require observers to rank the expression of sexually dimorphic skeletal traits by subjectively assessing their qualitative differences. One of these traits is the prominence of the glabellar region above the browridge. In this paper, the volume of the browridge region was measured from digital 3D models of 128 dry crania (65 female, 63 male). The 3D models were created with a desktop laser scanner, and the browridge region of each 3D model was isolated using geometric planes defined by cranial landmarks. Statistical analysis of browridge-to-cranium volume ratios revealed significant differences between male and female crania. Differences were also observed between geographically distinct populations, and between temporally distinct populations from the same locale. The results suggest that in the future, sex determination of human crania may be assisted by quantitative computer-based volume calculations from 3D models, which can provide increased objectivity and repeatability when compared to traditional forensic techniques. The method presented in this paper can easily be extended to other volumetric regions of the human cranium. PMID- 22776690 TI - Radiological status of the marine environment in the Barents Sea. AB - This paper presents the results of Norwegian radiological monitoring of the Barents Sea in 2007, 2008 and 2009. Activity concentrations of the anthropogenic radionuclides (137)Cs, (90)Sr, (239,240)Pu and (241)Am in seawater were low and up to an order of magnitude lower than in previous decades. Activity concentrations of (99)Tc in seawater were low but remain elevated compared to levels prior to the increased discharge of this radionuclide from Sellafield in the 1990s. Activity concentrations of the naturally occurring radionuclide (226)Ra in seawater were comparable to expected background values. Activity concentrations of (137)Cs in surface sediments were low, with higher values observed in sediments from coastal areas along the Norwegian mainland than from locations in the open sea. Activity concentrations of (137)Cs and (99)Tc in marine biota were low and up to an order of magnitude lower than in previous decades. Committed effective dose rates to man from anthropogenic radionuclides via the consumption of seafood from the Barents Sea were low and are not a cause for concern. Weighted absorbed dose rates to biota from anthropogenic radionuclides were low and orders of magnitude below a predicted no effect screening level of 10 MUGy/h. Dose rates to man from consumption of seafood and dose rates to biota in the marine environment are dominated by the contribution from naturally occurring radionuclides. PMID- 22776691 TI - 240Pu/239Pu mass ratio in environmental samples in Finland. AB - The (240)Pu/(239)Pu mass ratio was determined with SF-ICP-MS in lichen, peat, grass, air filter, and hot particle samples obtained in Finland. The main part of the air filters were sampled in northern Finland in 1963, whereas all the other samples were collected in southern and central Finland immediately after the Chernobyl accident in 1986. The (240)Pu/(239)Pu mass ratio varied between 0.13 +/ 0.01 and 0.53 +/- 0.03 in the environmental samples analyzed. The values for the (240)Pu/(239)Pu ratio confirm previous estimations, based on the (238)Pu/(239+240)Pu alpha activity ratio in the same samples, that global fallout from nuclear weapons testing and deposition from the Chernobyl accident have been the main Pu contamination sources in the environment in Finland. PMID- 22776692 TI - P2P watch: personal health information detection in peer-to-peer file-sharing networks. AB - BACKGROUND: Users of peer-to-peer (P2P) file-sharing networks risk the inadvertent disclosure of personal health information (PHI). In addition to potentially causing harm to the affected individuals, this can heighten the risk of data breaches for health information custodians. Automated PHI detection tools that crawl the P2P networks can identify PHI and alert custodians. While there has been previous work on the detection of personal information in electronic health records, there has been a dearth of research on the automated detection of PHI in heterogeneous user files. OBJECTIVE: To build a system that accurately detects PHI in files sent through P2P file-sharing networks. The system, which we call P2P Watch, uses a pipeline of text processing techniques to automatically detect PHI in files exchanged through P2P networks. P2P Watch processes unstructured texts regardless of the file format, document type, and content. METHODS: We developed P2P Watch to extract and analyze PHI in text files exchanged on P2P networks. We labeled texts as PHI if they contained identifiable information about a person (eg, name and date of birth) and specifics of the person's health (eg, diagnosis, prescriptions, and medical procedures). We evaluated the system's performance through its efficiency and effectiveness on 3924 files gathered from three P2P networks. RESULTS: P2P Watch successfully processed 3924 P2P files of unknown content. A manual examination of 1578 randomly selected files marked by the system as non-PHI confirmed that these files indeed did not contain PHI, making the false-negative detection rate equal to zero. Of 57 files marked by the system as PHI, all contained both personally identifiable information and health information: 11 files were PHI disclosures, and 46 files contained organizational materials such as unfilled insurance forms, job applications by medical professionals, and essays. CONCLUSIONS: PHI can be successfully detected in free-form textual files exchanged through P2P networks. Once the files with PHI are detected, affected individuals or data custodians can be alerted to take remedial action. PMID- 22776693 TI - Emerging mediators of airway smooth muscle dysfunction in asthma. AB - Phenotypic changes in airway smooth muscle are integral to the pathophysiological changes that constitute asthma - namely inflammation, airway wall remodelling and bronchial hyperresponsiveness. In vitro and in vivo studies have shown that the proliferative, secretory and contractile functions of airway smooth muscle are dysfunctional in asthma. These functions can be modulated by various mediators whose levels are altered in asthma, derived from inflammatory cells or produced by airway smooth muscle itself. In this review, we describe the emerging roles of the CXC chemokines (GROs, IP-10), Th17-derived cytokines (IL-17, IL-22) and semaphorins, as well as the influence of viral infection on airway smooth muscle function, with a view to identifying new opportunities for therapeutic intervention in asthma. PMID- 22776694 TI - Passive stiffness of airway smooth muscle: the next target for improving airway distensibility and treatment for asthma? AB - Reduced airway distensibility due to increased airway stiffness is a characteristic of asthma. Airway stiffness is determined by the property and structural organization of the various elements of the airway wall, and is often divided into active and passive components. Active stiffness is thought to be associated with activation of muscle cells in the airway wall. This component of stiffness can be inhibited when active force produced by the muscle is abolished. Passive stiffness, on the other hand, is thought to stem from non-muscle component of the airway wall, especially the collagen/elastin fibrous network of the extracellular matrix within which the muscle cells are embedded. In this brief review, the notion that passive stiffness is exclusively extracellular in origin is challenged. Recent evidence suggests that a substantial portion of the passive stiffness of an in vitro preparation of tracheal smooth muscle is calcium sensitive and is regulated by Rho-kinase, although the underlying mechanism and the details of regulation for the development of this intracellular passive stiffness are still largely unknown. To reduce airway stiffness different lines of attack must be tailored to different components of the stiffness. The regulatable passive stiffness is distinct from the relatively permanent stiffness of the extracellular matrix and the stiffness associated with active muscle contraction. To improve airway distensibility during asthma exacerbation, a comprehensive approach to reduce overall airway stiffness should therefore include a strategy for targeting the regulatable passive stiffness. PMID- 22776695 TI - Essential role of NR2B-containing NMDA receptor-ERK pathway in nucleus accumbens shell in morphine-associated contextual memory. AB - Learned associations between the rewarding effect of addictive drugs and drug paired contexts resist extinction and contribute to the high rate of relapse observed in drug addicts. Although it has been shown that extracellular signal regulated kinase 1/2 (ERK1/2) activity in the nucleus accumbens (NAc) is modulated by the primary rewarding effect of opiates, little is known as to its role in the morphine-associated contextual memory. In the present study, we investigated the ERK1/2 activity indicated by phosphorylated ERK1/2 (pERK1/2) levels in rats using a morphine-induced conditioned place preference (CPP) procedure. Our results showed that, in rats that had undergone morphine conditioning, after testing (expression phase) pERK1/2 in the NAc shell but not the NAc core or the adjacent caudate putamen was specifically increased. pERK1/2 levels in several other parts of the brain involved in drug-seeking, such as the medial prefrontal cortex, dorsal hippocampus, and basolateral amygdala, showed no significant changes. A significant positive correlation was observed between the elevated pERK1/2 level in the NAc shell and the degree of conditioned preference for morphine-associated contexts. Bilateral injection of an inhibitor of ERK activation into the NAc shell attenuated ERK1/2 phosphorylation and prevented the expression of morphine CPP, but injections into the core did not. Selective inhibition of NR2B-containing NMDA receptor in the NAc shell by ifenprodil prevented CPP expression and down-regulated local ERK1/2 phosphorylation. These findings collectively suggest that recall of morphine-associated contextual memory depends specifically upon ERK1/2 activation in the NAc shell and that ERK1/2 phosphorylation is regulated by the upstream NR2B-containing NMDA receptor. PMID- 22776696 TI - Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-alpha and interleukin-18 along with an inactivated vaccine. AB - BACKGROUND: Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI) H9N2 is a major concern for both animal and human health. Thus, an improved LPAI H9N2 vaccination strategy is needed to induce complete immunity in chickens against LPAI H9N2 virus strains. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. To improve the efficacy of inactivated LPAI H9N2 vaccine, attenuated Salmonella enterica serovar Typhimurium was used for oral co-administration of chicken interferon-alpha (chIFN-alpha) and chicken interleukin-18 (chIL-18) as natural immunomodulators. RESULTS: Oral co administration of S. enterica serovar Typhimurium expressing chIFN-alpha and chIL 18, prior to vaccination with inactivated AI H9N2 vaccine, modulated the immune response of chickens against the vaccine antigen through enhanced humoral and Th1 biased cell-mediated immunity, compared to chickens that received single administration of S. enterica serovar Typhimurium expressing either chIFN-alpha or chIL-18. To further test the protective efficacy of this improved vaccination regimen, immunized chickens were intra-tracheally challenged with a high dose of LPAI H9N2 virus. Combined administration of S. enterica serovar Typhimurium expressing chIFN-alpha and chIL-18 showed markedly enhanced protection compared to single administration of the construct, as determined by mortality, clinical severity, and feed and water intake. This enhancement of protective immunity was further confirmed by reduced rectal shedding and replication of AIV H9N2 in different tissues of challenged chickens. CONCLUSIONS: Our results indicate the value of combined administration of chIFN-alpha and chIL-18 using a Salmonella vaccine strain to generate an effective immunization strategy in chickens against LPAI H9N2. PMID- 22776697 TI - Porous silicon bulk acoustic wave resonator with integrated transducer. AB - : We report that porous silicon acoustic Bragg reflectors and AlN-based transducers can be successfully combined and processed in a commercial solidly mounted resonator production line. The resulting device takes advantage of the unique acoustic properties of porous silicon in order to form a monolithically integrated bulk acoustic wave resonator. PMID- 22776698 TI - A comparison of two methods in acquiring stimulus-response curves with transcranial magnetic stimulation. AB - BACKGROUND: The stimulus-response (S-R) curve is a well accepted constituent in transcranial magnetic stimulation (TMS) studies. However, it has been suggested that parameters of the S-R curve differ when stimuli are provided in a "ramped" (measured steps from low to high intensity), or "random" fashion. HYPOTHESIS: We hypothesized that there would be no difference in the parameters of the S-R curve between either methodologies. METHODS: Using a randomised cross-over design, 10 healthy participants (29.6 +/- 6.4 yrs, 3 f) completed "ramped" or "random" curves in biceps brachii (BB) and first dorsal interosseous (FDI) muscles of both limbs. Curves were compared using mixed-factor ANOVA and correlated between limbs and methodologies. RESULTS: No differences (P > 0.05) and high correlations (range 0.71-0.97; P < 0.001) were observed in BB and FDI data between curves. CONCLUSIONS: This study demonstrated that either methodology provides similar parameters of the S-R curve in healthy participants. PMID- 22776699 TI - Focus and selectivity in transcranial magnetic stimulation. PMID- 22776700 TI - Mapping early changes of cortical motor output after subcortical stroke: a transcranial magnetic stimulation study. AB - After acute stroke several changes in cortical excitability occur involving affected (AH) and unaffected hemisphere (UH) but whether they contribute to motor recovery is still controversial. We performed transcranial magnetic stimulation mapping of several upper limb muscles over the two hemispheres in thirteen patients at 4-12 days from subcortical stroke and after 1 month. The occurrence of mirror movements (MMs) on the healthy side during contraction of paretic muscles was measured. At baseline, cortical excitability parameters over the AH decreased in comparison with controls, while excitability over the UH increased correlating with severity of motor deficits of the affected arm at baseline as well as with poor recovery. At follow-up, map parameters of the UH became closer to those of controls independently from recovery, while for the AH the number of responsive sites increased significantly. Ipsilateral motor evoked responses (iMEPs) in the affected arm were never elicited. We observed an early impairment in dexterity of the ipsilesional hand that recovered over-time but persistently differed in comparison with controls. MMs occurrence increased at baseline correlating with reduced cortical excitability of the AH as well as with increased map density over the UH. The acute increased excitability of the UH after stroke has a negative prognostic value on recovery and negatively affects motor performance of the ipsilesional hand. Moreover, the absence of iMEPs and the normalization of motor cortical excitability at follow-up indicate that the UH primary motor area does not contribute to recovery. PMID- 22776701 TI - The relationship of global form and motion detection to reading fluency. AB - Visual motion processing in typical and atypical readers has suggested aspects of reading and motion processing share a common cortical network rooted in dorsal visual areas. Few studies have examined the relationship between reading performance and visual form processing, which is mediated by ventral cortical areas. We investigated whether reading fluency correlates with coherent motion detection thresholds in typically developing children using random dot kinematograms. As a comparison, we also evaluated the correlation between reading fluency and static form detection thresholds. Results show that both dorsal and ventral visual functions correlated with components of reading fluency, but that they have different developmental characteristics. Motion coherence thresholds correlated with reading rate and accuracy, which both improved with chronological age. Interestingly, when controlling for non-verbal abilities and age, reading accuracy significantly correlated with thresholds for coherent form detection but not coherent motion detection in typically developing children. Dorsal visual functions that mediate motion coherence seem to be related maturation of broad cognitive functions including non-verbal abilities and reading fluency. However, ventral visual functions that mediate form coherence seem to be specifically related to accurate reading in typically developing children. PMID- 22776703 TI - An analysis of Euroqol EQ-5D and Manchester Oxford Foot Questionnaire scores six months following podiatric surgery. AB - BACKGROUND: In the United Kingdom patient-reported outcome measures (PROMS) have been adopted as a key measure of foot surgery outcomes. The intention of this study was to evaluate the responsiveness of a regional outcome measure; the Manchester Oxford Foot Questionnaire (MOXFQ) and a generic measure; the EuroQol EQ-5D, in the context of day care Podiatric Surgery. METHODS: A prospective audit of 375 consecutive day care surgical admissions was undertaken. All patients attending for surgery, who agreed to participate, were included. Pre operation patients completed the MOXFQ and the EQ-5D. Both questionnaires were completed again at 6 months post operation. Additional data was collected on patient demographics, surgical procedures and complications. RESULTS: Few complications were encountered and most patients (84%) returned for a final review 6 months post operation. Mean MOXFQ scores improved for each domain: pain; 51.7 pre operation, reduced to 16.5 post-operation, walking; 50.2 reduced to 14.1 and social interaction; 45.7 reduced to 10.6. The minimal clinically important differences (MCID) estimates for the pain domain were exceeded by 82.6% of patients, while 74.8% exceeded the MCID for walking and 68.5% exceeded the MCID for social interaction. A small number of patients (2.9%) deteriorated across all three MOXFQ domains.The EQ-5D Index, summary of health related quality of life, improved from 0.66 pre-operation to 0.86 post operation. The EQ-5D index MCID was exceeded by 79.2% of patients. Index scores deteriorated for 1.8% of patients following surgery. Effect sizes measured following surgery were largest for the MOXFQ domains: Walking; 1.39, Pain; 1.52 and Social Interaction: 1.39. The EQ-5D index effect size was 0.83. The EQ-5D visual analogue scale (VAS) was not influenced by surgery. CONCLUSION: Both the MOXFQ and EQ-5D index (but not the VAS) appear sensitive to changes in health status at 6 months following elective foot surgery. Both instruments were particularly responsive to changes in pain, mobility and activity or social interaction following treatment. The MOXFQ was developed specifically for foot surgery and as such appears to be the more sensitive instrument. However the generic EQ-5D may allow comparison of general health states in the wider health community. Both instruments when used together appear well suited to the measurement of change in perceived health status following foot surgery. PMID- 22776704 TI - Neuroprotective effect of alpha-mangostin and curcumin against iodoacetate induced cell death. AB - Curcumin is a phenolic yellow curry pigment with anti-inflammatory and antioxidant activities and alpha-mangostin is a xanthone isolated from mangosteen fruit with antioxidant properties. Iodoacetate (IAA) is an inhibitor of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase that induces a model of metabolic inhibition in neurons where reactive oxygen species (ROS) production is a significant mechanism. Furthermore, it has been shown that the induction of heme oxygenase-1 (HO-1) protects against IAA-induced neuronal death. OBJECTIVES: To study the effects of alpha-mangostin and curcumin against the IAA-induced cell death and on HO-1 expression in primary cultures of cerebellar granule neurons (CGNs). METHODS: CGNs were treated with curcumin or alpha-mangostin before the addition of IAA. Cell viability and ROS production were measured 24 and 4 hours after IAA addition, respectively. HO-1 expression was measured by western blot. RESULTS: Both alpha-mangostin and curcumin pretreatment ameliorated the neuronal death induced by IAA in a concentration-dependent way, which was associated with an amelioration of IAA-induced ROS formation. In addition, it was found that alpha-mangostin and curcumin induced HO-1 expression. DISCUSSION: Treatment with alpha-mangostin and curcumin provided a neuroprotective effect against IAA in primary cultures of CGNs, an effect associated with an amelioration of the IAA-induced ROS production. HO-1 induced by these antioxidants may also be involved in the neuroprotective effect. Future work will be required to determine whether alpha-mangostin may cross the blood-brain barrier and achieve enough bioavailability to elicit a protective response in the brain being an effective nutraceutical compound for preventive therapy of neurodegenerative diseases. PMID- 22776705 TI - An evaluation study of EGFR mutation tests utilized for non-small-cell lung cancer in the diagnostic setting. AB - BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is predictive for the efficacy of EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer (NSCLC) treatment. We evaluated the performance, sensitivity, and concordance between five EGFR tests. MATERIALS AND METHODS: DNA admixtures (n = 34; 1%-50% mutant plasmid DNA) and samples from NSCLC patients [116 formalin fixed paraffin-embedded (FFPE) tissue, 29 matched bronchofiberscopic brushing (BB) cytology, and 20 additional pleural effusion (PE) cytology samples] were analyzed. EGFR mutation tests were PCR-Invader, peptide nucleic acid-locked nucleic acid PCR clamp, direct sequencing, Cycleave, and Scorpion Amplification Refractory Mutation System (ARMS). Analysis success, mutation status, and concordance rates were assessed. RESULTS: All tests except direct sequencing detected four mutation types at >=1% mutant DNA. Analysis success rates were 91.4%-100% (FFPE) and 100% (BB and PE cytology), respectively. Inter-assay concordance rates of successfully analyzed samples were 94.3%-100% (FFPE; kappa coefficients: 0.88-1.00), 93.1%-100% (BB cytology; 0.86-1.00), and 85.0%-100% (PE cytology; 0.70-1.00), and 93.1%-96.6% (0.86-0.93) between BB cytology and matched FFPE. CONCLUSIONS: All EGFR assays carried out comparably in the analysis of FFPE and cytology samples. Cytology-derived DNA is a viable alternative to FFPE samples for analyzing EGFR mutations. PMID- 22776706 TI - Multifocality and multicentricity in breast cancer and survival outcomes. AB - BACKGROUND: The clinicopathological characteristics and the prognostic significance of multifocal (MF) and multicentric (MC) breast cancers are not well established. PATIENTS AND METHODS: MF and MC were defined as more than one lesion in the same quadrant or in separate quadrants, respectively. The Kaplan-Meier product limit was used to calculate recurrence-free survival (RFS), breast cancer specific survival (BCSS), and overall survival (OS). Cox proportional hazards models were fit to determine independent associations of MF/MC disease with survival outcomes. RESULTS: Of 3924 patients, 942 (24%) had MF (n = 695) or MC (n = 247) disease. MF/MC disease was associated with higher T stages (T2: 26% versus 21.6%; T3: 7.4% versus 2.3%, P < 0.001), grade 3 disease (44% versus 38.2%, P < 0.001), lymphovascular invasion (26.2% versus 19.3%, P < 0.001), and lymph node metastases (43.1% versus 27.3%, P < 0.001). MC, but not MF, breast cancers were associated with a worse 5-year RFS (90% versus 95%, P = 0.02) and BCSS (95% versus 97%, P = 0.01). Multivariate analysis shows that MF or MC did not have an independent impact on RFS, BCSS, or OS. CONCLUSIONS: MF/MC breast cancers were associated with poor prognostic factors, but were not independent predictors of worse survival outcomes. Our findings support the current TNM staging system of using the diameter of the largest lesion to assign T stage. PMID- 22776707 TI - Centralised multidisciplinary re-evaluation of diagnostic procedures in patients with newly diagnosed Hodgkin lymphoma. AB - BACKGROUND: Hodgkin Lymphoma (HL) is highly curable when treated accurately. The challenge is to cure patients with the minimal risk of long-term complications. For that, optimal initial diagnostics are required to determine the optimal treatment plan. We offer non-academic hospitals in our Regional Comprehensive Cancer Centre network a centralised review of all diagnostic procedures from patients with newly diagnosed HL. We report our experience on concordances and discrepancies between local findings and central review results. PATIENTS AND METHODS: A haematologist and radiation oncologist at the Hodgkin Radboud University Nijmegen Medical Centre outpatient clinic examined all patients with newly diagnosed HL between February 2006 and May 2010. In a multidisciplinary lymphoma conference, diagnostic information is reviewed and treatment advice formulated. Discordant findings in pathology, staging and therapy were recorded as 'minor', no therapeutic consequences or 'major', adapted therapy advice. RESULTS: Altogether, 125 patients were included. Pathology review showed 86% concordance, with 4% major discordance, mainly nodular lymphocyte predominant sub type. Revision of initial staging was concordant in 77%; however 15% major discordance of which most were upstaged. This resulted in 19% treatment adaption. CONCLUSION: Our findings highlight the discrepancies in interpretation of diagnostic tests. We advocate centralised review process for all newly diagnosed patients with HL. PMID- 22776709 TI - The combined expression of Pdx1 and MafA with either Ngn3 or NeuroD improves the differentiation efficiency of mouse embryonic stem cells into insulin-producing cells. AB - The use of pancreatic beta-cells differentiated from embryonic stem (ES) cells or induced pluripotent stem (iPS) cells is a promising strategy in cell therapy. Pancreatic beta-cell development is regulated by the sequential expression of a molecular network of transcription factors. In this experiment, we adopted a three-step differentiation protocol to differentiate mES (mouse ES) cells into insulin-secreting cells and overexpressed transcription factors by adenoviral vectors at various combinations at different time of differentiation. We found that the coexpression of Pdx1 and MafA with either Ngn3 or NeuroD, especially at the final stage of the three-step differentiation, significantly increased the differentiation efficiency. It also increased the glucose-stimulated insulin and C-peptide secretion in insulin-secreting cells derived from mES cells compared to the control green fluorescent protein (GFP) vector-transduced group. For the first time, we have demonstrated that the coexpression of Pdx1 and MafA during a specific time window of development can act synergistically with either Ngn3 or NeuroD to promote the differentiation of mES cells into insulin-secreting cells. PMID- 22776708 TI - Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report. AB - BACKGROUND: Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). PATIENTS AND METHODS: Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. RESULTS: Ten-year cumulative incidence for chest wall recurrence of >15% was seen in patients aged <40 years (16.1%), with >=4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures >10%: >=4 positive nodes (10.2%); for axillary failures of >5%: aged <40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of >15% were age <40, peritumoral vessel invasion or 0 7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. CONCLUSION: PMRT to the chest wall and supraclavicular fossa is supported in patients with >=4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged <40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla. PMID- 22776710 TI - Effect of biochar amendment on the bioavailability of pesticide chlorantraniliprole in soil to earthworm. AB - To evaluate the effect of biochar amendment on the bioavailability of chlorantraniliprole (CAP) in soils with different physico-chemical properties, the uptake of CAP from various soils by earthworms was studied. It was observed that the biochar amendment of the soils affected the sorption of CAP, but the magnitude of the sorption enhancement by biochar amendment among the soils was varied, presumably due to the attenuation of the sorptivity of the biochar when amended in the soil. The amendment with biochars leads to a decrease in the bioavailability of CAP in the soils to earthworms, and more prominent for biochar BC850 amendment. In the soil with a CAP concentration of 10 mg kg(-1), the residue of CAP in the earthworm tissues was found to be 9.65 mg kg(-1), in comparison with that the CAP residue was 4.05 mg kg(-1) in BC450 amended soil and 0.59 mg kg(-1) in BC850, respectively. The degree of bioavailability reduction by same level of biochar amendment was different among soils with different properties. The results demonstrate that the properties of soils are important to performance of biochar in soil. PMID- 22776711 TI - Use of duckweed (Lemna disperma) to assess the phytotoxicity of the products of Fenton oxidation of metsulfuron methyl. AB - Because of pressure on water supplies world-wide, there is increasing interest in methods of remediating contaminated ground waters. However, with some remediation processes, the breakdown products are more toxic than the original contaminant. Organic matter and salinity may also influence degradation efficiency. This study tested the efficiency of Fenton oxidation in degrading the sulfonylurea herbicide metsulfuron methyl (MeS), and tested the reaction products for phytotoxicity with the Lemna (duckweed) bioassay. The efficiency of degradation by Fenton's reagent (Fe(2+)=0.09 mM; H(2)O(2)=1.76 mM, 4h) decreased with increasing initial MeS concentration, from 98% with 5 mg/L MeS, to 63% with 70 mg/L MeS. Addition of NaCl (10mM) and organic matter (humic acid at 0.2 and 2.0mg C/L as Total Organic Carbon) reduced the efficiency of degradation at low initial MeS concentrations (5 and 10 mg/L), but had no effect at high concentrations. The residual Fenton's reagent after Fenton's oxidation was toxic to Lemna. After removal of residual iron and H(2)O(2), the measured toxicity to Lemna in the treated samples could be explained by the concentrations of MeS as measured by HPLC/UV detection, so there was no evidence of additional toxicity or amelioration due to the by-products or formulation materials. PMID- 22776712 TI - The implementation of unit-based perinatal mortality audit in perinatal cooperation units in the northern region of the Netherlands. AB - BACKGROUND: Perinatal (mortality) audit can be considered to be a way to improve the careprocess for all pregnant women and their newborns by creating an opportunity to learn from unwanted events in the care process. In unit-based perinatal audit, the caregivers involved in cases that result in mortality are usually part of the audit group. This makes such an audit a delicate matter. METHODS: The purpose of this study was to implement unit-based perinatal mortality audit in all 15 perinatal cooperation units in the northern region of the Netherlands between September 2007 and March 2010. These units consist of hospital-based and independent community-based perinatal caregivers. The implementation strategy encompassed an information plan, an organization plan, and a training plan. The main outcomes are the number of participating perinatal cooperation units at the end of the project, the identified substandard factors (SSF), the actions to improve care, and the opinions of the participants. RESULTS: The perinatal mortality audit was implemented in all 15 perinatal cooperation units. 677 different caregivers analyzed 112 cases of perinatal mortality and identified 163 substandard factors. In 31% of cases the guidelines were not followed and in 23% care was not according to normal practice. In 28% of cases, the documentation was not in order, while in 13% of cases the communication between caregivers was insufficient. 442 actions to improve care were reported for 'external cooperation' (15%), 'internal cooperation' (17%), 'practice organization' (26%), 'training and education' (10%), and 'medical performance' (27%). Valued aspects of the audit meetings were: the multidisciplinary character (13%), the collective and non-judgmental search for substandard factors (21%), the perception of safety (13%), the motivation to reflect on one's own professional performance (5%), and the inherent postgraduate education (10%). CONCLUSION: Following our implementation strategy, the perinatal mortality audit has been successfully implemented in all 15 perinatal cooperation units. An important feature was our emphasis on the delicate character of the caregivers evaluating the care they provided. However, the actual implementation of the proposed actions for improving care is still a point of concern. PMID- 22776713 TI - Rubrobacter bracarensis sp. nov., a novel member of the genus Rubrobacter isolated from a biodeteriorated monument. AB - Three actinobacteria strains isolated from a green biofilm covering the biodeteriorated interior walls of Vilar de Frades Church (Portugal) were studied using a polyphasic approach. The three strains were aerobic, non-spore forming and Gram-positive. Phylogenetically, the most closely related described species was Rubrobacter radiotolerans (94.2-94.3% and 81.9-82.5% similarities for the 16S rRNA and rpoB gene sequences, respectively). The fatty acid profile was dominated by anteiso-C(17:1) omega9c, and MK-8 was the only menaquinone present. These data clearly showed that the three strains could represent a new species, for which we propose the name Rubrobacter bracarensis sp. nov., with strain VF70612_S1(T) (=CECT 7924=DSMZ 24908) as the type strain. PMID- 22776714 TI - Simultaneous infection of pigs and people with triple-reassortant swine influenza virus H1N1 at a U.S. county fair. AB - Influenza-like illness was noted in people and pigs in attendance at an Ohio county fair in August 2007. The morbidity rate in swine approached 100% within 1 2 days of initial clinical signs being recognized, and approximately two dozen people developed influenza-like illness. Triple-reassortant swine H1N1 influenza viruses were identified in both pigs and people at the fair. The identified viruses (A/Sw/OH/511445/2007, A/Ohio/01/2007, and A/Ohio/02/2007) were similar to H1N1 swine influenza viruses currently found in the U.S. swine population. This case illustrates the possibility of transmission of swine influenza in settings where there is close human/swine interaction. PMID- 22776715 TI - Structural basis for chirality and directional motility of Plasmodium sporozoites. AB - Plasmodium sporozoites can move at high speed for several tens of minutes, which is essential for the initial stage of a malaria infection. The crescent-shaped sporozoites move on 2D substrates preferably in the same direction on circular paths giving raise to helical paths in 3D matrices. Here we determined the structural basis that underlies this type of movement. Immature, non-motile sporozoites were found to lack the subpellicular network required for obtaining the crescent parasite shape. In vitro, parasites moving in the favoured direction move faster and more persistent than the few parasites that move in the opposite direction. Photobleaching experiments showed that sporozoites flip their ventral side up when switching the direction of migration. Cryo-electron tomography revealed a polarized arrangement of microtubules and polar rings towards the substrate in Plasmodium sporozoites, but not in the related parasite Toxoplasma gondii. As a consequence, secretory vesicles, which release proteins involved in adhesion, migration and invasion at the front end of the parasite, are delivered towards the substrate. The resulting chiral structure of the parasite appears to determine the unique directionality of movement and could explain how the sporozoite achieves rapid and sustained directional motility in the absence of external stimuli. PMID- 22776716 TI - Modeling and validation of on-road CO2 emissions inventories at the urban regional scale. AB - On-road emissions are a major contributor to rising concentrations of atmospheric greenhouse gases. In this study, we applied a downscaling methodology based on commonly available spatial parameters to model on-road CO(2) emissions at the 1 * 1 km scale for the Boston, MA region and tested our approach with surface-level CO(2) observations. Using two previously constructed emissions inventories with differing spatial patterns and underlying data sources, we developed regression models based on impervious surface area and volume-weighted road density that could be scaled to any resolution. We found that the models accurately reflected the inventories at their original scales (R(2) = 0.63 for both models) and exhibited a strong relationship with observed CO(2) mixing ratios when downscaled across the region. Moreover, the improved spatial agreement of the models over the original inventories confirmed that either product represents a viable basis for downscaling in other metropolitan regions, even with limited data. PMID- 22776717 TI - In contrast to sheep, goats adapt to dietary calcium restriction by increasing intestinal absorption of calcium. AB - Many studies aimed at understanding calcium homeostasis in the cow use sheep or goats as ruminant models. However, the comparability of relevant homeostatic processes between ruminant species has not been assessed. Therefore, we investigated whether the mechanisms of maintaining calcium homeostasis are similar in different ruminant species. Dietary calcium of goats was restricted along with treatment with calcitriol in a similar protocol to that in a recent study with sheep. Plasma calcium and phosphate and parameters of bone metabolism were analysed. Gastrointestinal calcium transport was characterised in vitro in Ussing chambers. The expression of apical epithelial calcium channels, calbindin D(9K), and the basolateral plasma membrane Ca(2+)-ATPase was determined by quantitative RT-PCR and Western blot analysis. In contrast to sheep, the goats were able to compensate for low dietary calcium supply by increasing active calcium absorption in the small intestine, especially in the jejunum. As in sheep, the observed ruminal calcium transport of goats was affected neither by the calcium restricted diet nor by the calcitriol treatment, thus indicating the presence of an alternative, vitamin D-independent mechanism of calcium transport in the forestomachs. These results demonstrate that mechanisms for maintaining calcium homeostasis differ significantly between ruminant species. PMID- 22776718 TI - Electrochemical and galvanic fabrication of a magnetoelectric composite sensor based on InP. AB - : A process chain for a magnetoelectric device based on porous InP will be presented using only chemical, electrochemical, photoelectrochemical, photochemical treatments and the galvanic deposition of metals in high-aspect ratio structures. All relevant process steps starting with the formation of a self-ordered array of current-line oriented pores followed by the membrane fabrication and a post-etching step, as well as the galvanic metal filling of membrane structures are presented and discussed. The resistivity of a porous InP structure could be drastically increased and, thus, the piezoelectric performance of the porous InP structure. The developed galvanic Ni filling process is capable to homogeneously fill high aspect-ratio membranes. PMID- 22776719 TI - In vitro intestinal transport of oligomeric procyanidins (DP 2 to 4) across monolayers of Caco-2 cells. AB - Extracts from hawthorn leafs and flowers (Crataegus sp., Rosaceae) are widely used as a rational based phytomedicine for declining cardiac performance. According to present literature C-glycosylated flavones and oligomeric procyanidins are considered to be the active ingredients, despite the fact that no systematic data are available on systemic bioavailability of proanthocyanidins after oral intake. The present study aims to review the actual state of literature in this field and to investigate the intestinal absorption mechanisms of defined hawthorn PAs with different degrees of polymerization by validated in vitro Caco-2 monolayer permeation system. Hawthorn OPCs with DP 2 to 6 were isolated as defined clusters. Procyanidin B2 and the procyanidin clusters DP 4, 5 and 6 had very low P(app) values between 0.6 and 6*10-7 cm/s for apical to basolateral permeation. The higher the molecular weight the lower permeation coefficients were calculated. The observed low-level transport was mainly due to passive paracellular permeation. Additionally cellular uptake of OPCs by transcellular permeation was possible; on the other side procyanidins were shown to be p-glycoprotein substrates, which leads to subsequent excretion of PAs by the efflux pump to the apical side. Mixtures of the different OPCs did not have an increased permeation. Transport experiments of complex OPC mixtures together with hawthorn flavonoids did not indicate any improved permeation or synergistic effects. In principle this raises the question if systemic pharmacological activities of hawthorn extracts, can really be attributed to OPCs with very low systemic bioavailability. PMID- 22776720 TI - Lathyrane diterpenes from Euphorbia prolifera and their inhibitory activities on LPS-induced NO production. AB - A new lathyrane diterpene (1), an unreported spectroscopic data lathyrane diterpenene (2), and two known analaogues (3 and 4) have been isolated from Euphorbia prolifera. Their structures were elucidated as (12E,2S,3S,4R,5R,6S,9S,11S,15R)-3-butyryloxy-5,15-diacetoxy-6,17-epoxylathyra- 12 en-14-one (1), (12E,2S,3S,4R,5R,6S,9S,11S,15R)-3-propionyloxy-5,15-diacetoxy-6,17 epoxylathyra-12-en-14-one (2), (12E,2S,3S,4R,5R,6S,9S,11S,15R)-3-benzoyloxy-5,15 diacetoxy -6,17-epoxylathyra-12-en-14-one (3), and 15-O-acetyl-17-hydroxyjolkinol (4) by spectroscopic methods (IR, ESIMS, HR-ESIMS, NMR, and X-ray crystallography). The inhibitory activities on LPS-induced NO production of these diterpenes were evaluated and compounds 1, 3 and 4 showed inhibitory effects. PMID- 22776721 TI - Feasibility study of EUS-NOTES as a novel approach for pancreatic cancer staging and therapy: an international collaborative study. AB - BACKGROUND/AIMS: EUS guided Natural Orifice Transluminal Endoscopic Surgery (NOTES) could be a potentially viable approach for pancreatic surgery. EUS-guided access through the stomach wall may prove to be a safe and effective method for accessing the pancreas. The aim of the study was to assess the EUS-guided diagnostic and therapeutic procedures during NOTES for both anterior and posterior approach of the pancreas. METHODOLOGY: The feasibility of peritoneoscopy through an anterior EUS-guided transgastric approach, as well as direct access to the pancreas through a posterior EUS-guided transgastric approach was tested for ease of access to the tail of the pancreas. Gastric wound closure was finally performed in several animals using various commercial and prototype endoscopic accessories. RESULTS: The results showed the ability of EUS NOTES technology to facilitate a transgastric approach and provide both an anterior and posterior access the pancreas. Identification the pancreatic tail by EUS with the aid of EUS-guided T-tag insertion, as well as posterior access and subsequent inspection/dissection of the pancreatic tail may also be possible. CONCLUSIONS: It is technically possible by EUS-guided NOTES procedures to achieve a systematic anterior and posterior access for NOTES transgastric peritoneoscopy and direct pancreatic endoscopic procedures. PMID- 22776722 TI - The Morphology Index: predictive value of malignancy among clinicians at various levels of training. AB - OBJECTIVE: To determine whether clinicians at various levels of training can reproduce and apply the Morphology Index when compared to Ueland's Morphology Index data, and to determine intra-observer variability when applied by observers at various levels of training. METHODS: One hundred four transvaginal ultrasound images of adnexal masses obtained at Indiana University between 1991 and 2003 were identified which had correlating surgical pathology. The images were scored by four investigators at four different levels of training. Scoring was based upon the revised University of Kentucky Morphology Index by Ueland. Each mass received 0-5 points for its structure, and 0-5 points for tumor volume. Each total score was then correlated with the surgical pathology. Sensitivity, specificity, positive predictive value and negative predictive value for each investigator were determined. All images were reviewed independently by each investigator; each was blinded to scores given by the other investigators and to final pathology. RESULTS: Nine malignant and 95 benign masses were noted on final pathology. Ranges for statistical values were: positive predictive value (PPV) 15 18%, negative predictive value (NPV) 93-98%, sensitivity 44-89%, and specificity 52-76%. CONCLUSION: The Morphology Index is a consistent and reliable tool for predicting benign disease demonstrating a high negative predictive value with little intra-observer variability. However, when predicting malignancy, the results showed more intra-observer variability and a positive predictive value half of that previously reported. This study confirms the clinical utility of the Morphology Index when utilized for its NPV and demonstrates its widespread application even among clinicians with minimal ultrasound training. PMID- 22776723 TI - Forage preservation (grazing vs. hay) fed to ewes affects the fatty acid profile of milk and CPT1B gene expression in the sheep mammary gland. AB - BACKGROUND: Alterations in lipid metabolism occur when animals are exposed to different feeding systems. In the last few decades, the characterisation of genes involved in fat metabolism and technological advances have enabled the study of the effect of diet on the milk fatty acid (FA) profile in the mammary gland and aided in the elucidation of the mechanisms of the response to diet. The aim of this study was to evaluate the effect of different forage diets (grazing vs. hay) near the time of ewe parturition on the relationship between the fatty acid profile and gene expression in the mammary gland of the Churra Tensina sheep breed. RESULTS: In this study, the forage type affected the C18:2 cis-9 trans-11 (CLA) and long-chain saturated fatty acid (LCFA) content, with higher percentages during grazing than during hay feeding. This may suggest that these FAs act as regulatory factors for the transcriptional control of the carnitine palmitoyltransferase 1B (CPT1B) gene, which was more highly expressed in the grazing group (GRE). The most highly expressed gene in the mammary gland at the fifth week of lactation is CAAT/ enhancer- binding protein beta (CEBPB), possibly due to its role in milk fat synthesis in the mammary gland. More stable housekeeping genes in the ovine mammary gland that would be appropriate for use in gene expression studies were ribosomal protein L19 (RPL19) and glyceraldehyde- 3- phosphate dehydrogenase (GAPDH). CONCLUSIONS: Small changes in diet, such as the forage preservation (grazing vs. hay), can affect the milk fatty acid profile and the expression of the CPT1B gene, which is associated with the oxidation of fatty acids. When compared to hay fed indoors, grazing fresh low mountain pastures stimulates the milk content of CLA and LCFA via mammary uptake. In this sense, LCFA in milk may be acting as a regulatory factor for transcriptional control of the CPT1B gene, which was more highly expressed in the grazing group. PMID- 22776725 TI - Analysis of alkyl phosphates in petroleum samples by comprehensive two dimensional gas chromatography with nitrogen phosphorus detection and post-column Deans switching. AB - Alkyl phosphate based gellants used as viscosity builders for fracturing fluids used in the process of hydraulic fracturing have been implicated in numerous refinery-fouling incidents in North America. In response, industry developed an inductively coupled plasma optical emission spectroscopy (ICP-OES) based method for the analysis of total volatile phosphorus in distillate fractions of crude oil; however, this method is plagued by poor precision and a high limit of detection (0.5+/-1MUg phosphorus mL(-1)). Furthermore this method cannot provide speciation information, which is critical for developing an understanding of the challenge of alkyl phosphates at a molecular level. An approach using comprehensive two-dimensional gas chromatography with nitrogen phosphorus detection (GC*GC-NPD) and post-column Deans switching is presented. This method provides qualitative and quantitative profiles of alkyl phosphates in industrial petroleum samples with increased precision and at levels comparable to or below those achievable by ICP-OES. A recovery study in a fracturing fluid sample and a profiling study of alkyl phosphates in four recovered fracturing fluid/crude oil mixtures (flowback) are also presented. PMID- 22776724 TI - Current management of massive hemorrhage in trauma. AB - Hemorrhage remains a major cause of potentially preventable deaths. Trauma and massive transfusion are associated with coagulopathy secondary to tissue injury, hypoperfusion, dilution, and consumption of clotting factors and platelets. Concepts of damage control surgery have evolved prioritizing early control of the cause of bleeding by non-definitive means, while hemostatic control resuscitation seeks early control of coagulopathy.Hemostatic resuscitation provides transfusions with plasma and platelets in addition to red blood cells in an immediate and sustained manner as part of the transfusion protocol for massively bleeding patients. Although early and effective reversal of coagulopathy is documented, the most effective means of preventing coagulopathy of massive transfusion remains debated and randomized controlled studies are lacking. Viscoelastical whole blood assays, like TEG and ROTEM however appear advantageous for identifying coagulopathy in patients with severe hemorrhage as opposed the conventional coagulation assays.In our view, patients with uncontrolled bleeding, regardless of it's cause, should be treated with hemostatic control resuscitation involving early administration of plasma and platelets and earliest possible goal directed, based on the results of TEG/ROTEM analysis. The aim of the goal directed therapy should be to maintain a normal hemostatic competence until surgical hemostasis is achieved, as this appears to be associated with reduced mortality. PMID- 22776726 TI - Magnetic molecularly imprinted polymer for the detection of rhaponticin in Chinese patent medicines. AB - The magnetic molecularly imprinted polymers (MMIPs) had been synthesized for the selective extraction and clean-up of rhaponticin in Chinese patent medicines (CPM). The MMIPs were prepared via suspension polymerization, using Fe(3)O(4) as magnetically component, rhaponticin as template molecule, acrylamide (AM) as functional monomers, styrene (St) as copolymer monomer and ethylene glycol dimethacrylate (EGDMA) as a cross-linker in dimethyl sulfoxide porogen. The obtained MMIPs were characterized using scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). High performance liquid chromatography (HPLC) was used for analysis the target analytes. The polymers were evaluated further by batch rebinding experiments. From the derived Freundlich isotherm (FI) equation their binding capacity and binding strength were determined. Structurally similar compound resveratrol and a reference compound kirenol were used for investing the selective recognition capability of MMIPs. The MMIPs were used as sorbents for selective pre-concentration of rhaponticin from CPM samples. The contents of rhaponticin for the four CPM samples were found to be 11.84, 3.35, 4.47, and 7.57MUg g(-1), respectively, and the recoveries of spiked samples ranged from 77.82% to 91.00%. The prepared MMIPs could be applied to selectively pre concentrate and determine rhaponticin in CPM samples. PMID- 22776727 TI - Exploring the human urine metabolomic potentialities by comprehensive two dimensional gas chromatography coupled to time of flight mass spectrometry. AB - Metabolomics represents an emerging issue that can aid in the diagnosis and/or prognosis of different diseases. Metabolomic study of urine is particularly interesting as it can be on the base of the developing of new faster and non invasive methodologies. In response to this actual trend, comprehensive two dimensional gas chromatography-time of flight mass spectrometry (GC*GC-ToFMS) combined with headspace solid phase microextraction (HS-SPME) is applied, for the first time to our knowledge, to the untargeted and comprehensive study of the volatile composition of human urine. From a total of ca. 700 compounds detected per sample, 294 were tentatively identified and distributed over the chemical families of hydrocarbons, amines, amides, esters, ketones, aldehydes, alcohols, carboxylic acids, ethers, nitriles, halides, sulfides, thiols, terpenoids, and heterocyclic compounds. To our knowledge, this is the most complete information available so far about whole human urine volatile composition, which represents a valuable data for future advanced studies in the clinical field based on urine fingerprinting. Relevant SPME and GC*GC parameters were considered. Complex sample characterization of human urine is significantly simplified due to the structured GC*GC chromatogram that produces distinct spaces for metabolite chemical families. Furthermore, the potential of this methodology in health related applications was explored by comparing the urinary volatile profiles between smoker (high-risk population for lung cancer) vs. non-smoker adults, focusing on metabolites related to oxidative stress (aliphatic alkanes and aldehydes). In spite of the small sample numbers considered, the results suggest that the urinary volatile profiles may be useful for differentiating subjects with different physiological conditions, thus making it worth to further explore its diagnostic potential. PMID- 22776728 TI - Surgical management of solitary venous malformation in the midcheek region. AB - OBJECTIVE: The aim of this study was to analyze a single institution's experience of solitary venous malformation (VM) in the midcheek region. STUDY DESIGN: From 2002 to 2009, a total of 10 consecutive patients with solitary venous malformation in the midcheek region were retrospectively analyzed. Clinical records were reviewed for patient demographic data, presenting symptoms and signs, imaging modalities used, histologic and immunohistochemical results, surgical data, and clinical outcomes. RESULTS: The sample consisted of 5 males and 5 females with a mean age of 42.8 years. The course of disease ranged from 0.5 to 144.0 months with a mean time of 64.9 months. The mean size of the masses was 1.7 * 1.5 cm (range 1.0 * 0.8 cm to 2.5 * 2.5 cm). Investigations included Doppler ultrasonography (US) and computed tomography (CT) scanning. Surgical excision using various surgical approaches was performed in all patients. Postoperative pathologic examination confirmed the diagnosis of VM. The mean follow-up period was 41.2 months (range 2 months to 94 months) with no recurrence reported. CONCLUSIONS: For solitary VM in the midcheek region, investigations, such as Doppler US or CT scanning or the use of fine-needle aspiration cytology, may aid in clinical diagnosis. The primary treatment of these lesions is surgical excision, and in our sample, the prognosis of such treatment was good with no recurrence reported. PMID- 22776729 TI - The 3D CT superimposition method using image fusion based on the maximum mutual information algorithm for the assessment of oral and maxillofacial surgery treatment results. AB - OBJECTIVE: The usefulness of image fusion based on the maximum mutual information algorithm was investigated for the assessment of oral and maxillofacial surgery treatment results. STUDY DESIGN: Superimposition was performed using image fusion of 25 CBCT images of a human skull under the assumption of different spatial conditions and 41 patients' image data. Errors were measured using distances between titanium markers on the skull. The degree of shared image information was defined as normalized mutual information (NMI) value to assess robustness of image fusion. RESULTS: The mean error was 0.396 mm (+/- 0.142 mm) and was not affected by positional change (P > .05). Mandibular shifts showed significantly different (P = .000) NMI values but shared information was not significantly affected by the degree of surgical changes in patients' CT (P = .176). CONCLUSIONS: For the evaluation of surgical treatment results, image fusion is an accurate and reliable method that is not affected by spatial or surgical changes. PMID- 22776731 TI - Combination of intermittent hydrostatic pressure linking TGF-beta1, TNF-alpha on modulation of proteoglycan 4 metabolism in rat temporomandibular synovial fibroblasts. AB - OBJECTIVE: This study was designed to evaluate the combined effects of intermittent hydrostatic pressure (IHP) and TGF-beta1 or TNF-alpha on proteoglycan4 (PRG4) expression in rat temporomandibular synovial fibroblasts (SFs). STUDY DESIGN: Rat SFs were isolated and expanded in monolayer cultures and subjected to IHP in the presence of TGF-beta1 or TNF-alpha. Quantitative real time RT-PCR was applied to analyze the PRG4 expression levels. Enzyme-linked immunosorbent assay was also used for the quantification of PRG4 accumulation in the culture medium while immunofluorescence staining was used to detect intracellular PRG4 protein expression. RESULTS: The combination of IHP and TGF beta1 induced greater PRG4 expression than either stimulus alone. In contrast, TNF-alpha inhibited PRG4 expression, and this was partially alleviated by IHP. CONCLUSIONS: Our study demonstrates a beneficial role of IHP, which can be used successfully in combination with TGF-beta1 to enhance PRG4 production, and can partially counteract TNF-alpha-induced PRG4 inhibition in isolated rat SFs. PMID- 22776730 TI - Using computer simulation and stereomodel for accurate mandibular reconstruction with vascularized iliac crest flap. AB - OBJECTIVES: The aim of this study was to examine our patients who underwent accurate mandibular reconstruction with vascularized iliac crest flap using computer simulation and stereomodel and assess the postoperative results. STUDY DESIGN: Fourteen patients were reviewed in this study. Bilateral iliac crests were automatically superimposed on the mandibular defects to select the optimal matching donor region in computer simulation. Operation was performed using stereomodels to replicate the preoperative planning. Actual reconstruction result was compared with computer simulation. The patients were asked to assess their satisfaction with facial appearance at 1 year after surgery. RESULTS: Bony unions and good occlusion were observed, and actual results were basically in accordance with computer simulation in 14 patients. Fourteen patients reported their facial appearance to be excellent or good at 1 year after surgery. CONCLUSIONS: Accurate mandibular reconstruction with vascularized iliac crest flap using computer simulation and stereomodel may achieve the ideal contour of neomandible and good function after dental rehabilitation. PMID- 22776732 TI - Ossifying fibroma of the jaws: a clinical study of 14 cases and review of the literature. AB - OBJECTIVE: The purpose of this study was to evaluate the clinical outcomes of ossifying fibroma (OF) in a group of 14 patients treated in our clinic and discuss the management and the prognosis of this tumor. STUDY DESIGN: The study included 14 consecutive patients with OF of the jaws with ages ranging from 7 to 55 years. Primary site distribution was maxilla (1), maxilla, maxillary sinus (1), and mandible (12). All of the patients treated by surgery (curettage, enucleation, or radical surgery). RESULTS: The mean follow-up range was 2-18 years. All of the patients were alive and disease free. CONCLUSIONS: OF is a benign slow-growing tumor of the jaws. Early tumors that are small or well demarcated are treated by curettage or enucleation. For aggressive tumors that show rapid enlargement, radical resection (maxillectomy or segmental mandibulectomy) is used. By either method of treatment, the recurrence rate is extremely low. PMID- 22776733 TI - Is atopy the common factor mediating changes in the prevalence of different allergic diseases? PMID- 22776734 TI - White-tailed deer (Odocoileus virginianus) as a potential sentinel for human Lyme disease in Indiana. AB - We assessed the potential of white-tailed deer (WTD) (Odocoileus virginianus) to be a sentinel for human cases of Lyme disease (LD) in Indiana using location data from a 3-year survey of approximately 3400 hunted deer with associated tick Ixodes scapularis and Borrelia burgdorferi (Bb) data. Data on human LD cases at the county level were obtained from the Indiana Department of Health. All data were assigned to county centroids to match the resolution of the LD data before creating optimized trend surfaces for LD incidence, hunted deer count, Ixodes scapularis and Bb prevalence. To determine whether LD was spatially associated with the areas of high densities of deer, deer with Ixodes scapularis and deer with ticks infected with Bb, we used spatial analysis with distance indices (SADIE). The SADIE analysis found significant spatial association between LD and the distribution of three organismal predictor variables, that is, WTD, Ixodes ticks and Bb. Lyme disease incident rate varied between 0.08 cases per 10,000 habitants (Johnson county) and 5.9 cases per 10,000 habitants (Warren county). In conclusion, WTD can be used as an accurate and cost-effective sentinel for human LD. This method will permit public health workers to identify potentially endemic areas independently of human case reports. PMID- 22776735 TI - The X-ray crystal structure of a pseudoazurin from Sinorhizobium meliloti. AB - The X-ray crystal structure of oxidised pseudoazurin from the denitrifying plant symbiotic bacterium Sinorhizobium meliloti (SmPAz2) has been solved to a resolution of 2.0 A. The pseudoazurin from Sinorhizobium sp. is unusual as it forms an operon with a sulfite dehydrogenase enzyme, rather than a Cu nitrite reductase. Examination of the structure reveals that the geometric parameters of the Type I Cu site in SmPAz2 correlate with observed features in the electronic spectrum of the protein. Comparison of the structure of SmPAz2 with those of pseudoazurins from five other bacterial species shows that the surface of SmPAz2 bears a conserved hydrophobic patch encircled by positively-charged residues, which may serve as a recognition site for its redox partners. PMID- 22776736 TI - Application of a design of experiment approach in the development of a sensitive bioanalytical assay in human plasma. AB - To support a first-in-human (FIH) clinical study in healthy volunteers, a human plasma assay, a 20-fold more sensitive method than the validated non-clinical LC MS/MS assays, was requested. For the clinical assay, a LLOQ of 0.050 ng/mL for Compound A and 0.100 ng/mL for Compound B was desired to accurately determine the analyte concentrations in human plasma samples across all treatment groups. A design of experiment (DOE) investigation was performed in an effort to optimize the extraction procedure of the bioanalytical assay used to support the first in human study and future clinical studies. Three factors, extraction buffer pH (two pHs), volume ratio of organic solvent to plasma (two ratios), and extraction shake time (three times), were selected for the DOE. Both analytes were analyzed at a low concentration, 0.150 ng/mL, and a stable isotope label internal standard was used for each analyte. To estimate the recovery of each analyte from the extraction, the response ratio of each analyte over the respective internal standard was used, and to estimate matrix effects, the absolute response (peak area) of each analyte was used. The results of the DOE indicated that the three factors tested had a more significant effect on the extraction of the metabolite, Compound B, compared to that of the parent, Compound A. The extraction buffer pH had the greatest influence on Compound B and the volume of extraction solvent had an influence on both analytes. Unexpectedly, a longer extraction time caused an apparent decrease in the overall recovery for both analytes. This was presumably due to an increased extraction of interfering matrix components. Optimal conditions were achieved for the combined analysis of both compounds using the DOE approach. PMID- 22776738 TI - Study on the adsorption property of lysozyme on weak cation exchanger based on monodisperse poly(glycidymethacrylate-co-ethylenedimethacrylate) beads. AB - A type of weak cation exchanger was prepared based on poly(glycidylmethacrylate co-ethylenedimethacrylate). The effects of pH and ionic strength on the adsorption behavior were studied, and the results suggested that the adsorption of lysozyme onto a weak cation exchanger is electrostatic interaction, and that the adsorption behavior is in accordance with the Langmuir adsorption model with a correlation coefficient greater than 0.99. It was also found that increasing ionic strength led to a decrease of the adsorption of lysozyme from 49.50 to 28.09 mg/g. Preliminary chromatographic experiments were conducted to test the separation properties of the weak cation exchanger, and the results demonstrated that the retention time of different proteins could be predicted in order of their isoelectric point. PMID- 22776737 TI - Monitoring batch-to-batch reproducibility of liquid-liquid extraction process using in-line near-infrared spectroscopy combined with multivariate analysis. AB - Traditional Chinese medicine (TCM) products are usually manufactured through batch processes. To improve batch-to-batch reproducibility, the feasible approaches for real-time monitoring of batch evolution need to be developed. In line near-infrared (NIR) spectroscopy combined with multivariate data analysis as an efficient process analytical technology (PAT) tool, is presented in this study for real-time batch process monitoring. Liquid-liquid extraction is a widely used purification technology in the TCM manufacture, and selected as the example to demonstrate the effectiveness of this PAT tool. Multi-way partial least squares (MPLS) model was developed based on in-line measured NIR spectral data of ten normal operation condition (NOC) batches. Three kinds of multivariate control charts (scores, Hotelling T(2) and DModX) were used to monitor the evolution of six test batches with artificial batch variations, including the change of starting material quality attributes and abnormal operation conditions. The approach was found very effective for real-time monitoring of process deviations from NOC batches. It is an alternative promising tool for monitoring batch reproducibility of the unit operations during the manufacture of TCM. PMID- 22776739 TI - Determination of polycyclic aromatic hydrocarbons in fresh milk by hollow fiber liquid-phase microextraction-gas chromatography mass spectrometry. AB - In this work, a two-phase hollow fiber liquid-phase microextraction (HF-LPME) method combined with gas chromatography-mass spectrometry (GC-MS) is developed to provide a rapid, selective and sensitive analytical method to determine polycyclic aromatic hydrocarbons (PAHs) in fresh milk. The standard addition method is used to construct calibration curves and to determine the residue levels for the target analytes, fluorene, phenanthrene, fluoranthene, pyrene and benzo[a]pyrene, thus eliminating sample pre-treatment steps such as pH adjustment. The HF-LPME method shows dynamic linearity from 5 to 500 ug/L for all target analytes with R(2) ranging from 0.9978 to 0.9999. Under optimized conditions, the established detection limits range from 0.07 to 1.4 ug/L based on a signal-to-noise ratio of 3:1. Average relative recoveries for the determination of PAHs studied at 100 ug/L spiking levels are in the range of 85 to 110%. The relative recoveries are slightly higher than those obtained by conventional solvent extraction, which requires saponification steps for fluorene and phenanthrene, which are more volatile and heat sensitive. The HF-LPME method proves to be simple and rapid, and requires minimal amounts of organic solvent that supports green analysis. PMID- 22776740 TI - Rationale for mitochondria-targeting strategies in cancer bioenergetic therapies. AB - In the 1920s, Otto Warburg first hypothesized that mitochondrial impairment is a leading cause of cancer although he recognized the existence of oxidative tumors. Likewise, Weinhouse and others in the 50s found that deficient mitochondrial respiration is not an obligatory feature of cancer and Peter Vaupel suggested in the 1990s that tumor oxygenation rather than OXPHOS capacity was the limiting factor of mitochondrial energy production in cancer. Recent studies now clearly indicate that mitochondria are highly functional in mice tumors and the field of oncobioenergetic identified MYC, Oct1 and RAS as pro-OXPHOS oncogenes. In addition, cancer cells adaptation to aglycemia, metabolic symbiosis between hypoxic and non-hypoxic tumor regions as well the reverse Warburg hypothesis support the crucial role of mitochondria in the survival of a subclass of tumors. Therefore, mitochondria are now considered as potential targets for anti-cancer therapy and tentative strategies including a bioenergetic profile characterization of the tumor and the subsequent adapted bioenergetic modulation could be considered for cancer killing. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. PMID- 22776741 TI - Cardiac mitochondrial dysfunction during hyperglycemia--the role of oxidative stress and p66Shc signaling. AB - Diabetes mellitus is a chronic disease caused by a deficiency in the production of insulin and/or by the effects of insulin resistance. Insulin deficiency leads to hyperglycemia which is the major initiator of diabetic cardiovascular complications escalating with time and driven by many complex biochemical and molecular processes. Four hypotheses, which propose mechanisms of diabetes associated pathophysiology, are currently considered. Cardiovascular impairment may be caused by an increase in polyol pathway flux, by intracellular advanced glycation end-products formation or increased flux through the hexosamine pathway. The latter of these mechanisms involves activation of the protein kinase C. Cellular and mitochondrial metabolism alterations observed in the course of diabetes are partially associated with an excessive production of reactive oxygen species (ROS). Among many processes and factors involved in ROS production, the 66 kDa isoform of the growth factor adaptor shc (p66Shc protein) is of particular interest. This protein plays a key role in the control of mitochondria-dependent oxidative balance thus it involvement in diabetic complications and other oxidative stress based pathologies is recently intensively studied. In this review we summarize the current understanding of hyperglycemia induced cardiac mitochondrial dysfunction with an emphasis on the oxidative stress and p66Shc protein. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. PMID- 22776742 TI - QT interval prolongation by acute gastrointestinal bleeding in patients with cirrhosis. AB - BACKGROUND & AIMS: QT interval prolongation is frequent in cirrhosis, and stressful conditions could further prolong QT. We aimed to test this hypothesis and, if it proved correct, to assess its prognostic meaning. METHODS: We reviewed the clinical records of 70 consecutive cirrhotic and 40 non-cirrhotic patients with acute gastrointestinal bleeding. All patients had been evaluated before bleeding (T0) and were re-evaluated at the time of bleeding (T1) and 6 weeks afterwards (T2). RESULTS: QT corrected by heart rate (QTc) lengthened at T1, returning towards baseline values at T2 (mean +/- SEM; from 415.9 +/- 4.3 to 453.4 +/- 4.3 to 422.2 +/- 5.7 ms, P < 0.001) in cirrhotics; contrariwise, QTc did not change in non-cirrhotic patients. The 6-week mortality was 29.6% among cirrhotic patients, while no control patient died. At T1, patients who died had longer QTc (P = 0.001) and higher model of end-stage liver disease (MELD) score (P < 0.001) than survivors. MELD and QTc independently predicted survival. Their areas under the ROC curve were 0.88 (CI 95% 0.78-0.95) and 0.75 (CI 95% 0.63 0.85) respectively; the best cut-off values were MELD >=20 and QTc >= 460 ms. Based on these factors, the 6-week mortality was: 0% for patients without risk factors, 32.1% for those with one risk factor and 70.6% for those with both (P < 0.001). CONCLUSIONS: Acute gastrointestinal bleeding further prolongs QTc in cirrhosis. This abnormality independently predicts bleeding-induced mortality. The combined measurement of QTc interval and MELD can clearly identify three patient strata at increasing risk of bleeding-related mortality, thus improving the decision-making for these patients. PMID- 22776743 TI - STR and mitochondrial DNA SNP typing of a bone marrow transplant recipient after death in a fire. AB - Personal identification of a house fire victim is described. About 5 years prior to death, the victim had been underwent bone marrow transplantation (BMT) with a graft from an unrelated donor as treatment for acute myelogenous leukemia. Clinically, the victim had been in remission at the time of death. Typing of STRs and sequencing of mitochondrial DNA (mtDNA) were performed using blood from the heart as well as several soft (psoas major muscle, uterine muscle and mucous membrane of the urinary bladder) and hard (costal cartilage and nail) tissues. STR genotypes and amelogenin from each of the tissue samples were successfully typed, and the parentage was identified. The blood STR types demonstrated no relationship with those from other tissues. None of the blood STR loci showed extra peaks arising from those of the recipient. Therefore, the blood stem cells were assumed to have been altered to those of the donor. The genotypes of mtDNA control regions were also examined. The electropherogram of hypervariable region II (nucleotide positions 29-408) obtained from the blood revealed a similar length heteroplasmy, suggesting microchimerism of the blood. Sequence analysis of mtDNA might be applicable as a more sensitive method for determination of chimerisms after BMT. PMID- 22776744 TI - Improved cell survival and paracrine capacity of human embryonic stem cell derived mesenchymal stem cells promote therapeutic potential for pulmonary arterial hypertension. AB - Although transplantation of adult bone marrow mesenchymal stem cells (BM-MSCs) holds promise in the treatment for pulmonary arterial hypertension (PAH), the poor survival and differentiation potential of adult BM-MSCs have limited their therapeutic efficiency. Here, we compared the therapeutic efficacy of human embryonic stem cell-derived MSCs (hESC-MSCs) with adult BM-MSCs for the treatment of PAH in an animal model. One week following monocrotaline (MCT)-induced PAH, mice were randomly assigned to receive phosphate-buffered saline (MCT group); 3.0*10(6) human BM-derived MSCs (BM-MSCs group) or 3.0*10(6) hESC-derived MSCs (hESC-MSCs group) via tail vein injection. At 3 weeks post-transplantation, the right ventricular systolic pressure (RVSP), degree of RV hypertrophy, and medial wall thickening of pulmonary arteries were lower=, and pulmonary capillary density was higher in the hESC-MSC group as compared with BM-MSC and MCT groups (all p < 0.05). At 1 week post-transplantation, the number of engrafted MSCs in the lungs was found significantly higher in the hESC-MSC group than in the BM-MSC group (all p < 0.01). At 3 weeks post-transplantation, implanted BM-MSCs were undetectable whereas hESC-MSCs were not only engrafted in injured pulmonary arteries but had also undergone endothelial differentiation. In addition, protein profiling of hESC-MSC- and BM-MSC-conditioned medium revealed a differential paracrine capacity. Classification of these factors into bioprocesses revealed that secreted factors from hESC-MSCs were preferentially involved in early embryonic development and tissue differentiation, especially blood vessel morphogenesis. We concluded that improved cell survival and paracrine capacity of hESC-MSCs provide better therapeutic efficacy than BM-MSCs in the treatment for PAH. PMID- 22776745 TI - Improving data quality and supervision of antiretroviral therapy sites in Malawi: an application of Lot Quality Assurance Sampling. AB - BACKGROUND: High quality program data is critical for managing, monitoring, and evaluating national HIV treatment programs. By 2009, the Malawi Ministry of Health had initiated more than 270,000 patients on HIV treatment at 377 sites. Quarterly supervision of these antiretroviral therapy (ART) sites ensures high quality care, but the time currently dedicated to exhaustive record review and data cleaning detracts from other critical components. The exhaustive record review is unlikely to be sustainable long term because of the resources required and increasing number of patients on ART. This study quantifies the current levels of data quality and evaluates Lot Quality Assurance Sampling (LQAS) as a tool to prioritize sites with low data quality, thus lowering costs while maintaining sufficient quality for program monitoring and patient care. METHODS: In January 2010, a study team joined supervision teams at 19 sites purposely selected to reflect the variety of ART sites. During the exhaustive data review, the time allocated to data cleaning and data discrepancies were documented. The team then randomly sampled 76 records from each site, recording secondary outcomes and the time required for sampling. RESULTS: At the 19 sites, only 1.2% of records had discrepancies in patient outcomes and 0.4% in treatment regimen. However, data cleaning took 28.5 hours in total, suggesting that data cleaning for all 377 ART sites would require over 350 supervision-hours quarterly. The LQAS tool accurately identified the sites with the low data quality, reduced the time for data cleaning by 70%, and allowed for reporting on secondary outcomes. CONCLUSIONS: Most sites maintained high quality records. In spite of this, data cleaning required significant amounts of time with little effect on program estimates of patient outcomes. LQAS conserves resources while maintaining sufficient data quality for program assessment and management to allow for quality patient care. PMID- 22776746 TI - Response to novelty in the laboratory Wistar rat, wild-captive WWCPS rat, and the gray short-tailed opossum (Monodelphis domestica). AB - Behavior of the laboratory gray short-tailed opossums (Monodelphis domestica), Warsaw Wild Captive Pisula Stryjek rats (WWCPS) and laboratory rats (Wistar) has been registered in the period of familiarization with a new environment and consecutive confrontation with a novel, innocuous object placed in that familiarized environment. In the new environment the sequence of anxiety, investigation, and habituation was shortest in the opossum, longer in the laboratory rat and longest in the WWCPS rat. When placed in it, gray short-tailed opossums investigated the new environment with the shortest delay and most intensity. In reaction to novel objects, opossums and laboratory rats prolonged the time spent in the proximity of the new object, while the WWCPS rat did not show that reaction. Both opossums and laboratory rats increased the number of contacts with the new object, whereas WWCPS rats reduced those contacts. Behavior of all three species and lines grouped in different clusters. Some other quantitative and qualitative differences in behavior of the investigated animals are also described, showing a higher level of anxiety in both lines of rats than in the opossum. Behavioral differences between species and lines of animals used in this study may be attributed to different ecological adaptations of rats and opossums and to the effect of domestication in the laboratory rats. These behavioral differences make comparisons of opossums vs rat, and wild rat vs laboratory rat interesting models for studying the brain mechanisms of anxiety and neotic motivations. PMID- 22776747 TI - Modification of cellulosic fibers by UV-irradiation. Part II: after treatments effects. AB - This work presents the comparative study on the dyeing behavior of cellulose fibers in alkaline solutions and under the influence of UV radiation. The cellulosic fabrics were pretreated followed by conventional mercerization technique or treatment with UV irradiation. For different time duration the reorganization of cellulose fibers by swelling treatments in alkaline solutions results in numerous structural modifications, causing changes of their accessibility and/or reactivity. The results revealed that the swelling of the cellulosic fibers depends on type of pre-treatment, dose of the radiation and the concentration of alkaline solution used. SEM analysis confirmed that UV irradiation of the cellulosic fibers leads to a higher swelling in comparison with any concentration of NaOH treatment. In comparison of both the treatments, the mercerized cellulosic fibers have shown better tear and tensile strength as compared to the untreated and UV irradiated one. There is adverse effect of UV radiation on the mechanical properties of UV radiation. Moreover, no loss in weight was observed after exposing the cellulose fabrics surface to UV radiation. PMID- 22776748 TI - Advances in biomedical applications of pectin gels. AB - Pectin, due to its simple and cytocompatible gelling mechanism, has been recently exploited for different biomedical applications including drug delivery, gene delivery, wound healing and tissue engineering. Recent studies involving pectin for the biomedical field are reviewed, with the aim to capture the state of art on current research about pectin gels for biomedical applications, moving outside the traditional fields of application such as the food industry or pharmaceutics. Pectin structure, sources and extraction procedures have been discussed focussing on the properties of the polysaccharide that can be tuned to optimize the gels for a desired application and possess a fundamental role in application of pectin in the biomedical field. PMID- 22776749 TI - Molecular epidemiology of canine norovirus in dogs from Portugal, 2007-2011. AB - BACKGROUND: Canine noroviruses (NoVs) have been recently described in south European countries and associated with outbreaks of diarrhea in kennels. Unlike human NoV which are known as an important cause of acute gastroenteritis, little is known about the role of canine NoV as pathogens in dogs as well as its epidemiological features. RESULTS: From 2007-2011, 256 stool samples were collected from dogs across Portugal and tested by RT-PCR for canine NoV. Viral fecal shedding was found to be 23% (60/256). All sequences contained the GLPSG amino acid motif characteristic of the RNA-dependent RNA-polymerase gene of NoVs and had a high nucleotide identity (range 98%-100%) to the canine NoV first described in Portugal. The highest shedding rate was detected during the winter months. CONCLUSIONS: This study shows that canine NoV infection is endemic in the dog population of Portugal. Peak shedding was detected in the winter months, a well-known epidemiologic feature of human NoV infections. PMID- 22776750 TI - Follicular fluid concentrations of IGF-I, IGF-II, IGFBP-3, VEGF, AMH, and inhibin B in women undergoing controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist. AB - OBJECTIVE: To compare follicular fluid concentrations of IGF-I, IGF-II, IGFBP-3, inhibin-B, VEGF, and AMH in women undergoing controlled ovarian hyperstimulation with a long-luteal GnRH agonist protocol or multiple-dose GnRH antagonist protocol. STUDY DESIGN: A total of 80 cycles were included; long-luteal GnRH agonist group (n=40) and multiple dose GnRH antagonist group (n=40). All follicular fluid samples were obtained from mature follicles during oocyte retrieval. IGF-I and IGFBP-3 concentrations were measured by immunoradiometric assay. IGF-II, VEGF, AMH, and inhibin-B concentrations were measured by enzyme linked immunosorbent assay. RESULTS: There were no significant differences in the concentrations of the studied follicular fluid markers, cycle parameters, and treatment outcomes between GnRH agonist and GnRH antagonist protocols. CONCLUSIONS: The long-luteal GnRH agonist protocol and multiple-dose GnRH antagonist protocol seem to have similar effects on the follicular microenvironment in women undergoing controlled ovarian hyperstimulation. PMID- 22776751 TI - The strategies that peanut and nut-allergic consumers employ to remain safe when travelling abroad. AB - BACKGROUND: An understanding of the management strategies used by food allergic individuals is needed as a prerequisite to improving avoidance and enhancing quality of life. Travel abroad is a high risk time for severe and fatal food allergic reactions, but there is paucity of research concerning foreign travel. This study is the first to investigate the experiences of, and strategies used by peanut and tree nut allergic individuals when travelling abroad. METHODS: Thirty two adults with a clinical history of reaction to peanuts or tree nuts consistent with IgE-mediated allergy participated in a qualitative interview study. RESULTS: Travel abroad was considered difficult with inherent risks for allergic individuals. Many participants recounted difficulties with airlines or restaurants. Inconsistency in managing allergen avoidance by airlines was a particular risk and a cause of frustration to participants. Individuals used a variety of strategies to remain safe including visiting familiar environments, limiting their activities, carrying allergy information cards in the host language, preparing their own food and staying close to medical facilities. CONCLUSIONS: Participants used a variety of allergen avoidance strategies, which were mostly extensions or modifications of the strategies that they use when eating at home or eating-out in the UK. The extended strategies reflected their recognition of enhanced risk during travel abroad. Their risk assessments and actions were generally well informed and appropriate. A need for airline policy regarding allergy to be declared and adhered to is needed, as is more research to quantify the true risks of airborne allergens in the cabin. Recommendations arising from our study are presented. PMID- 22776752 TI - Diagnostic value of 13N-ammonia myocardial perfusion PET: added value of myocardial flow reserve. AB - The ability to obtain quantitative values of flow and myocardial flow reserve (MFR) has been perceived as an important advantage of PET over conventional nuclear myocardial perfusion imaging (MPI). We evaluated the added diagnostic value of MFR over MPI alone as assessed with (13)N-ammonia and PET/CT to predict angiographic coronary artery disease (CAD). METHODS: Seventy-three patients underwent 1-d adenosine stress-rest (13)N-ammonia PET/CT MPI, and MFR was calculated. The added value of MFR as an adjunct to MPI for predicting CAD (luminal narrowing >= 50%) was evaluated using invasive coronary angiography as a standard of reference. RESULTS: Per patient, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MPI for detecting significant CAD were 79%, 80%, 91%, 59%, and 79%, respectively. Adding a cutoff of less than 2.0 for global MFR to MPI findings improved the values to 96% (P < 0.005), 80%, 93%, 89% (P < 0.005), and 92% (P < 0.005), respectively. CONCLUSION: The quantification of MFR in (13)N-ammonia PET/CT MPI provides a substantial added diagnostic value for detection of CAD. Particularly in patients with normal MPI results, quantification of MFR helps to unmask clinically significant CAD. PMID- 22776753 TI - Journal of Pediatric Urology. Editorial. PMID- 22776754 TI - Impaired facial emotion recognition in a ketamine model of psychosis. AB - OBJECTIVE: Social cognitive disabilities are a common feature in schizophrenia. Given the role of glutamatergic neurotransmission in schizophrenia-related cognitive impairments, we investigated the effects of the glutamatergic NMDA receptor antagonist ketamine on facial emotion recognition. METHODS: Eighteen healthy male subjects were tested on two occasions, one without medication and one after administration with subanesthetic doses of intravenous ketamine. Emotion recognition was examined using the Ekman 60 Faces Test. In addition, attention was measured by the Continuous Performance Test (CPT), and psychopathology was rated using the Psychotomimetic States Inventory (PSI). RESULTS: Ketamine produced a non-significant deterioration of global emotion recognition abilities. Specifically, the ability to correctly identify the facial expression of sadness was significantly reduced in the ketamine condition. These results were independent of psychotic symptoms and selective attention. CONCLUSION: Our results point to the involvement of the glutamatergic system in the ability to recognize facial emotions. PMID- 22776755 TI - Interpersonal reassurance seeking in obsessive-compulsive disorder and its relationship with checking compulsions. AB - This study aimed to examine interpersonal reassurance seeking (IRS) in obsessive compulsive disorder (OCD) and the relationship between IRS and checking compulsions. One hundred and forty adults with OCD underwent a comprehensive assessment, which included obtaining information on seeking reassurance from others because of their obsessions. Sixty-seven (47.9%) participants reported IRS. They exhibited more psychopathology than participants without IRS, tended to have a greater overall severity of OCD and were far more likely to have checking compulsions. Participants with IRS also had more severe obsessions, suggesting that IRS plays a role as an additional coping strategy when obsessions are more prominent. The severity of obsessions and the absence of obsessions about a need to collect and keep objects were independent predictors of IRS, whereas the presence of obsessions about unintentional harm and not being married or in a de facto relationship independently predicted checking compulsions. Although a close relationship exists between IRS and checking compulsions, these results suggest important differences, with implications for understanding the factors that contribute to IRS and checking compulsions. PMID- 22776756 TI - Optimization of water quality monitoring network in a large river by combining measurements, a numerical model and matter-element analyses. AB - A monitoring network that resolves the spatial and temporal variations of the water quality is essential in the sustainable management of water resources and pollution control. Due to cost concerns, it is important to optimize the monitoring locations so to use the least number of stations required to obtain the most comprehensive monitoring. The optimal design of monitoring networks is commonly based on the limited data available from existing measuring stations. The main contribution of this paper is the use of a numerical water quality model, calibrated with the available data. This model yields information on the water quality in any cross-section along the river, including the river reaches that are not monitored. Another contribution of the paper is the use of a matter element analysis that allows for an objective division of the river in reaches that are homogeneous with respect to the water quality as assessed from multiple water quality parameters. The optimal monitoring network consists of one measuring station in each of these homogeneous reaches. The method has been applied to optimize the water quality monitoring network on the 1890 km long upper and middle reaches of the Heilongjiang River in Northeast China. The results suggest that the monitoring network improves considerably by relocating three stations, and not by adding extra stations. PMID- 22776757 TI - The intrinsic features of Environmental Management Systems that facilitate adoption and encourage innovation in primary industries. AB - This paper examines the theoretical underpinnings of the adoption of innovations, and applies this knowledge to the uptake of Environmental Management Systems (EMS) amongst Australian farmers. We examine the specific features of the EMS process that might encourage or inhibit EMS adoption. We also consider elements of the EMS process to assess their utility in promoting adoption of various other innovations. We evaluate the EMS process in the light of two characteristics previously found to influence adoption of improved natural resource management practices - 'relative advantage' and 'trialability'. Drawing on literature, and our research and experience with farmers, we conclude that there are inherent features of EMS that promote the adoption of new practices, and that the elements of the EMS process actually create an on-going process of culture change as it is implemented. We believe that the EMS process offers significant advantages to farmers seeking to improve production whilst simultaneously meeting societal expectations for enhanced natural resource management. PMID- 22776758 TI - Environmental improvement of product supply chains: proposed best practice techniques, quantitative indicators and benchmarks of excellence for retailers. AB - Retailers are strategically positioned to leverage environmental improvement over product supply chains through actions targeted at suppliers and consumers. Informed by scientific evidence on environmental hotspots and control points across 14 priority product groups, and a review of 25 major European retailers' actions, this paper proposes a framework to guide and assess retailer best practice in supply chain environmental improvement. Commonly used product standards and improvement measures are classified into "basic" or "good" levels of environmental protection. A hierarchy of eight Best Environmental Management Practices (BEMPs) is proposed to systematically identify and improve the most environmentally damaging supply chains across retail assortments. Widespread third party environmental certification is the most transparent and verifiable mechanism of improvement but may not be appropriate for some supply chains. The enforcement of retailer-defined environmental requirements, and supplier improvement programmes based on performance benchmarking and dissemination of better management practices, are alternative BEMPs that may be used in combination with third party certification. Facilitating consumer selection of frontrunner ecological products is a lower priority BEMP owing to the well documented limitations of this approach. From available data, the highest current or credible-target sales shares of products improved according to the highest priority BEMP and environmental protection level were used to derive "benchmarks of excellence" for each of the 14 product groups. The assessment framework is demonstrated through application to three retailers. PMID- 22776759 TI - Computer-based identification of a novel LIMK1/2 inhibitor that synergizes with salirasib to destabilize the actin cytoskeleton. AB - Neurofibromin regulates cell motility via three distinct GTPase pathways acting through two different domains, the Ras GTPase-activating protein-related domain (GRD) and the pre-GRD domain. First, the GRD domain inhibits Ras-dependent changes in cell motility through the mitogen activated protein cascade. Second, it also regulates Rho-dependent (Ras-independent) changes by activating LIM kinase 2 (LIMK2), an enzyme that phosphorylates and inactivates cofilin (an actin depolymerizing factor). Third, the pre-GRD domain acts through the Rac1 GTPase, that activate the P21 activated kinase 1 (PAK1)-LIMK1-cofilin pathway. We employed molecular modeling to identify a novel inhibitor of LIMK1/2. The active sites of an ephrin-A receptor (EphA3) and LIMK2 showed marked similarity (60%). On testing a known inhibitor of EphA3, we found that it fits to the LIMK1/2-ATP binding site and to the latter's substrate-binding pockets. We identified a similar compound, T56-LIMKi, and found that it inhibits LIMK1/2 kinase activities. It blocked the phosphorylation of cofilin which led to actin severance and inhibition of tumor cell migration, tumor cell growth, and anchorage-independent colony formation in soft agar. Because modulation of LIMK by neurofibromin is not affected by the Ras inhibitor Salirasib, we examined the combined effect of Salirasib and T56-LIMKi each of which can affect cell motility by a distinct pathway. We found that their combined action on cell proliferation and stress-fiber formation in neurofibromin-deficient cells was synergistic. We suggest that this drug combination may be developed for treatment of neurofibromatosis and cancer. PMID- 22776760 TI - Novel uromodulin mutation in familial juvenile hyperuricemic nephropathy. AB - BACKGROUND: Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder characterized by early onset of hyperuricemia, decreased fractional renal urate excretion and progressive interstitial nephropathy. Mutations in the uromodulin (UMOD) gene encoding uromodulin/Tamm-Horsfall, a glycosylphosphatidylinositol (GPI)-anchored protein, cause this disease. METHODS: One Chinese family with 13 FJHN-affected individuals is described. Clinical data, blood and urine samples of 7 affected members (all alive patients in this family) and 15 unaffected members were collected. Mutation analysis of the UMOD gene was performed by polymerase chain reaction and direct sequencing. Urinary uromodulin from affected or unaffected members of this family and healthy controls was examined by enzyme-linked immunosorbent assay kit. Expression of uromodulin in renal tissue was shown with immunofluorescence. RESULTS: A novel mutation (p.T605G) within the uromodulin GPI anchor signal segment was identified in the affected individuals of this FJHN family. There was a markedly increased expression of uromodulin in renal tissue and significantly decreased urinary excretion of uromodulin in affected patients with an estimated glomerular filtration rate <60 ml/min/1.73 m(2). CONCLUSIONS: The present study reported a novel mutation in exon 9 of UMOD in the Chinese Han population, within the GPI anchor signal segment of uromodulin. Since the GPI anchor is linked with the release or secretion of proteins, our finding may provide further evidence for the underlying mechanism of decreased urinary excretion of uromodulin in FJHN. PMID- 22776761 TI - Decision support by telephone: randomized controlled trial in a rural community setting. AB - OBJECTIVE: Our community-based participatory research partnership previously evaluated Consultation Planning (CP), a question-listing intervention delivered in-person. We now report on effectiveness, cost, and value of delivering CP by telephone (Tele-CP). METHODS: Between 2007 and 2010, we randomly assigned rural women with a diagnosis of breast cancer to receive Tele-CP or In-Person CP. We compared ratings of decision self-efficacy (0 minimum to 4 maximum) with a pre specified non-inferiority margin of 15%. We also explored psychosocial and economic outcomes. RESULTS: Tele-CP (n=35) recipients reported mean decision self efficacy ratings of 3.53 versus 3.44 for in-person (n=32). Under intent-to-treat analysis, we rejected the null hypothesis of greater than 0.52 inferiority for Tele-CP (95% CI for difference: -0.44 to 0.13, p=0.006). The intervention costs averaged $48 for Tele-CP versus $78 in-person (95% CI for difference: -$63 to $2). Mean willingness-to-pay was $154 for Tele-CP and $144 for in-person (95% CI for difference: -$88 to $108). CONCLUSION: Tele-CP was non-inferior to In-Person CP, cost no more, and was equally valued by patients. PRACTICE IMPLICATIONS: Telephone delivery of Consultation Planning can achieve comparable quality, cost, and value as in-person. Organizations offering Consultation Planning or similar question-listing interventions should consider adopting telephone delivery. PMID- 22776762 TI - Patients, providers, and relationships in healthcare: investigations from the ICCH 2011 conference in Chicago. PMID- 22776765 TI - ABC transporters, CYP1A and GSTalpha gene transcription patterns in developing stages of the Nile tilapia (Oreochromis niloticus). AB - In fish, some ABC transporters are implicated in a multixenobiotic resistance (MXR) mechanism to deal with the presence of xenobiotics, by effluxing them, or their metabolites, from inside the cells. These efflux transporters have been considered an integral part of cellular detoxification pathways, acting in coordination with phase I and II detoxification enzymes. However, the full characterization of this detoxification system is still incomplete, especially during the developmental stages of aquatic organisms, which are particularly sensitive periods to the presence of anthropogenic contamination. The goal of this study was to evaluate the mRNA expression dynamics of putatively important MXR proteins (ABCB1b, ABCB11, ABCC1, ABCC2 and ABCG2a) and phase I (CYP1A) and II (GSTalpha) biotransformation enzymes, during the embryonic and larval developments of the specie Oreochromis niloticus (Nile tilapia). Our results showed that ABCB1b, ABCC1, CYP1A and GSTalpha transcripts are maternally transmitted. Transcripts for ABCB11, ABCC2 and ABCG2a were only detected after the pharyngula period, which precedes a highly sensitive stage in the embryonic development, the hatching. This study has shown, for the first time, very distinct expression patterns of genes encoding for proteins involved in protection mechanisms against pollutants during the development of Nile tilapia. Moreover, the temporal pattern of gene expression suggests that increased intrinsic protection levels are required at specific developmental stages. PMID- 22776766 TI - An improved heuristic for haplotype inference. AB - Haplotypes include essential SNP information used for a variety of purposes such as investigating potential links between certain diseases and genetic variations. Given a set of genotypes, the haplotype inference problem based on pure parsimony is the problem of finding a minimum set of haplotypes that explains all the given genotypes. The problem is especially important because, while it is fairly inexpensive to obtain genotypes, other approaches to obtaining haplotypes are significantly expensive. There are two types of methods proposed for the problem, namely exact and inexact methods. Existing exact methods guarantee obtaining purely parsimonious solutions but have exponential time-complexities and are not practical for large number or length of genotypes. However, inexact methods are relatively fast but do not always obtain optimum solutions. In this paper, an improved heuristic is proposed, based on which new inexact and exact methods are provided. Experimental results indicate that the proposed methods replace the state-of-the-art inexact and exact methods for the problem. PMID- 22776767 TI - Diffusion-weighted MRI of the testis in hydrocele: a pilot study. AB - OBJECTIVE: To investigate the effects of increased pressure due to the accumulated fluid around testis in hydrocele on testis diffusion and whether this effect (if any) is correlated with the amount of fluid and duration of hydrocele. PATIENTS AND METHOD: 49 patients with unilateral hydrocele were evaluated by magnetic resonance diffusion-weighted imaging. RESULTS: In the study group, while the apparent diffusion coefficient (ADC) values of the testicles with hydrocele differed significantly before and 3 months after the hydrocelectomy (p = 0.001), the ADC values of the testicles without hydrocele were not statistically different (p = 0.101). There was a significant negative correlation between the ADC values of the testicles with hydrocele and the amount of the liquid aspirated during the hydrocelectomy (r = -0.615, p = 0.001). There was no correlation between the ADC values of testis and the duration of hydrocele (r = -287, p = 0.156). This is supported by the findings of the present study of reduced ADC values of testis, meaning reduced diffusion of the testis, with an increasing amount of fluid. CONCLUSION: The pressure of the fluid was suggested to show a mechanical effect that plays an important role in the dysfunction of the testis. The possible dysfunctions of the testicular tissue suggest that they may have a negative effect on fertility. PMID- 22776768 TI - Lack of CYP1A responsiveness in species inhabiting chronically contaminated habitats: two varieties of resistance? AB - Organisms chronically exposed to organic pollutants such as polychlorinated biphenyls (PCBs) can develop resistance to these chemicals, a condition associated with reduced inducibility of the biomarker enzyme cytochrome P450 1A (CYP1A). This study addresses the CYP1A response of members of the families Ictaluridae and Centrarchidae, two fish families found throughout much of the United States. We measured CYP1A expression, PCB body burdens, and conducted CYP1A challenge experiments in species from these families residing in the Town Branch/Mud River system (Logan County, KY, USA), a stream system historically contaminated with high levels of PCBs. Despite PCB concentrations in muscle tissue typically associated with elevated CYP1A (16.7 to 75.2MUgPCB/g wet edible flesh), resident fish in the contaminated Town Branch/Mud River sites (yellow bullhead [Ameiurus natalis], green sunfish [Lepomis cyanellus], and spotted bass [Micropterus punctulatus]) had hepatic CYP1A activity levels similar to, rather than higher than, those in reference fish, suggesting reduced sensitivity to CYP1A induction. Lack of CYP1A expression following direct contaminant exposure has often been associated with resistance to those contaminants. To determine if CYP1A in resident populations was resistant to induction by PCBs, we exposed resident fish to a single, intraperitoneal injection with a potent CYP1A inducer, 3,4,3',4'-tetrachlorobiphenyl (PCB 77). PCB 77 treatment significantly induced hepatic CYP1A activity and protein in yellow bullhead from reference, but not contaminated, sites and had no effect on CYP1A in green sunfish from either site. The low CYP1A expression levels in resident fish with elevated PCB body burdens, together with the failure of PCB injection to induce CYP1A in certain populations, indicate an acclimatory CYP1A response in yellow bullheads and likely an inherently resistant CYP1A in green sunfish. This work demonstrates for the first time acclimation of CYP1A to PCBs in a species within the family Ictaluridae and provides further support for our previous work indicating an apparent inherent lack of CYP1A sensitivity to chlorinated inducers in Centrarchids. These traits may explain, at least in part, the common association of these families with degraded habitats and indicate Lepomis members are likely to be excellent candidates for exploring the mechanistic basis of 'inherent' CYP1A resistance. This study also underlines to the need for thorough characterization of the CYP1A responsivity of a population and/or species prior to using CYP1A as a reliable biomonitoring tool. PMID- 22776769 TI - Alginate scaffolds for mesenchymal stem cell cardiac therapy: influence of alginate composition. AB - Despite the success of alginate scaffolds and mesenchymal stem cells (MSCs) therapy in cardiac failure treatment, the impact of the physicochemical environment provided by alginate matrices on cell behavior has never been investigated. The purpose of this work was double: to determine the alginate composition influence on (1) encapsulated rat MSC viability, paracrine activity, and phenotype in vitro and (2) cardiac implantability and in vivo biocompatibility of patch shape scaffolds. Two alginates, differing in composition and thus presenting different mechanical properties when hydrogels, were characterized. In both cases, encapsulated MSC viability was maintained at around 75%, and their secretion characteristics were retained 28 days postencapsulation. In vivo study revealed a high cardiac compatibility of the tested alginates: cardiac parameters were maintained, and rats did not present any sign of infection. Moreover, explanted hydrogels appeared surrounded by a vascularized tissue. However, scaffold implantability was highly dependent on alginate composition. G-type alginate patches, presenting higher elastic and Young moduli than M-type alginate patches, showed a better implantation easiness and were the only ones that maintained their shape and morphology in vivo. As a consequence of alginate chemical composition and resulting hydrogel structuration, G-type alginate hydrogels appear to be more adapted for cardiac implantation. PMID- 22776770 TI - Transcriptome analysis of head kidney in grass carp and discovery of immune related genes. AB - BACKGROUND: Grass carp (Ctenopharyngodon idella) is one of the most economically important freshwater fish, but its production is often affected by diseases that cause serious economic losses. To date, no good breeding varieties have been obtained using the oriented cultivation technique. The ability to identify disease resistance genes in grass carp is important to cultivate disease resistant varieties of grass carp. RESULTS: In this study, we constructed a non normalized cDNA library of head kidney in grass carp, and, after clustering and assembly, we obtained 3,027 high-quality unigenes. Solexa sequencing was used to generate sequence tags from the transcriptomes of the head kidney in grass carp before and after grass carp reovirus (GCRV) infection. After processing, we obtained 22,144 tags that were differentially expressed by more than 2-fold between the uninfected and infected groups. 679 of the differentially expressed tags (3.1%) mapped to 483 of the unigenes (16.0%). The up-regulated and down regulated unigenes were annotated using gene ontology terms; 16 were annotated as immune-related and 42 were of unknown function having no matches to any of the sequences in the databases that were used in the similarity searches. Semi quantitative RT-PCR revealed four unknown unigenes that showed significant responses to the viral infection. Based on domain structure predictions, one of these sequences was found to encode a protein that contained two transmembrane domains and, therefore, may be a transmembrane protein. Here, we proposed that this novel unigene may encode a virus receptor or a protein that mediates the immune signalling pathway at the cell surface. CONCLUSION: This study enriches the molecular basis data of grass carp and further confirms that, based on fish tissue-specific EST databases, transcriptome analysis is an effective route to discover novel functional genes. PMID- 22776771 TI - Assessment of an uncalibrated pressure waveform device's ability to track cardiac output changes due to norepinephrine dose adjustments in patients with septic shock: a comparison with Doppler echocardiography. AB - OBJECTIVES: The FloTrac Vigileo (FTV) estimates cardiac output (CO) on the basis of an uncalibrated arterial pressure waveform. To assess the ability of the third generation of FTV (v.3.02) to track changes in CO following norepinephrine dose adjustment in patients with septic shock, we performed a comparative study using Doppler echocardiography (DE). STUDY DESIGN: Prospective observational study. PATIENTS: We prospectively included 20 mechanically ventilated patients receiving norepinephrine and monitored with the FTV. Five minutes after each change in norepinephrine dose (decided by the attending physician), CO was measured simultaneously with the FTV (CO(FTV)) and DE (CO(DE)). The changes in CO were compared. ROC curves were built to assess the ability of FTV to detect significant changes in CO(DE) of at least 15%. RESULTS: Ninety pairs of CO variations measurements were made. The intertechnique correlation coefficient for changes in CO of at least 15% was r=0.59; P=0.0009. The AUC of a ROC curve built to test the FTV's ability to detect a CO(DE) increase of 15% or more was 0.783 (+/-0.083) (P=0.005). A CO(FTV) threshold value of 15% had a sensitivity of 54% (25-81) and a specificity of 87% (77-94). For a CO(DE) decrease of 15% or more, the ROC curve had an AUC of 0.616 (+/-0.075) (P=0.12) and a CO(FTV) threshold value of 13% yielded a sensitivity of 53% (27-79) and a specificity of 72% (60 82). CONCLUSIONS: The FTV was unable to accurately track changes in CO following norepinephrine dose adjustments in critically ill patients with septic shock. PMID- 22776772 TI - [General anaesthesia in children: a French survey of practices]. AB - INTRODUCTION: The practice of pediatric anesthesia requires a regular update of scientific knowledge and technical skills. To provide the most adequate Continuing Medical Education programs, it is necessary to assess the practices of pediatric anesthesiologists. Thus, the objective of this survey was to draw a picture of the current clinical practices of general anesthesia in children, in France. MATERIAL AND METHODS: One thousand one hundred and fifty questionnaires were given to anesthesiologists involved in pediatric cases. These questionnaires collected information on various aspects of clinical practice relative to induction, maintenance, recovery from general anaesthesia and also classical debated points such as children with Upper Respiratory Infection (URI), emergence agitation, epileptoid signs or anaesthetic management of adenoidectomy. Differences in practices between CHG (general hospital), CHU (teaching hospital), LIBERAL (private) and PSPH (semi-private) hospitals were investigated. RESULTS: There were 1025 questionnaires completed. Fifty-five percent of responders worked in public hospitals (CHG and CHU); 77% had a practice that was 25% or less of pediatric cases. In children from 3 to 10 years: 72% of respondents used always premedication and two thirds performed inhalation induction in more than 50% of cases. For induction, 53% used sevoflurane (SEVO) at 7 or 8%. Respondents from LIBERAL used higher SEVO concentrations. Tracheal intubation was performed with SEVO alone (37%), SEVO and propofol (55%) and SEVO with myorelaxant (8%), 93% of respondents used a bolus of opioid. For maintenance, the majority of respondents used SEVO associated with sufentanil; desflurane and remifentanil were more frequently used in CHU. Two thirds of respondents used N(2)O. Depth of anesthesia was commonly assessed by hemodynamic changes (52%), end tidal concentration of halogenated (38%) or automated devices based on EEG (7%). In children with URI, 98% of respondents used SEVO for anesthesia. To control the airway 42% used a tracheal tube, 30% a laryngeal mask and 20% a facial mask. Emergence agitation was an important concern for two thirds of respondents, while epileptoid signs were considered as important by only 20%. Eighty-nine percent of respondents practiced anesthesia for adenoidectomy. Anesthesia was induced by inhalation of SEVO 7-8% (41%), 6% (39%) or 4% (12%), 66% put an intravenous line (less frequently in LIBERAL). 67% of the responders managed adenoidectomy without any device to control the airway (more frequently in LIBERAL), 32% administrated a bolus of opioid (less frequently in LIBERAL). DISCUSSION: This survey demonstrated that the practices regarding general anesthesia in children are relatively homogenous. Most of the differences appeared between LIBERAL and the others structures; the anaesthetic management for adenoidectomy illustrates these findings. PMID- 22776773 TI - Hydrogen-rich water inhibits glucose and alpha,beta -dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Leprcp/NDmcr rat kidney. AB - BACKGROUND: Reactive oxygen species (ROS) production induced by alpha,beta dicarbonyl compounds and advanced glycation end products causes renal dysfunction in patients with type 2 diabetes and metabolic syndrome. Hydrogen-rich water (HRW) increases the H2 level in blood and tissues, thus reducing oxidative stress in animals as well as humans. In this study, we investigated the effects of HRW on glucose- and alpha,beta-dicarbonyl compound-induced ROS generation in vitro and in vivo. METHODS: Kidney homogenates from Wistar rats were incubated in vitro with glucose and alpha,beta-dicarbonyl compounds containing HRW, following which ROS levels were measured. In vivo animal models of metabolic syndrome, SHR.Cg Leprcp/NDmcr rats, were treated with HRW for 16 weeks, following which renal ROS production and plasma and renal alpha,beta-dicarbonyl compound levels were measured by liquid chromatograph mass spectrometer. RESULTS: HRW inhibited glucose- and alpha,beta-dicarbonyl compound-induced ROS production in kidney homogenates from Wistar rats in vitro. Furthermore, SHR.Cg-Leprcp/NDmcr rats treated with HRW showed a 34% decrease in ROS production. Moreover, their renal glyoxal, methylglyoxal, and 3-deoxyglucosone levels decreased by 81%, 77%, and 60%, respectively. Positive correlations were found between renal ROS levels and renal glyoxal (r = 0.659, p = 0.008) and methylglyoxal (r = 0.782, p = 0.001) levels. CONCLUSION: These results indicate that HRW inhibits the production of alpha,beta-dicarbonyl compounds and ROS in the kidneys of SHR.Cg-Leprcp/NDmcr rats. Therefore, it has therapeutic potential for renal dysfunction in patient with type 2 diabetes and metabolic syndrome. PMID- 22776763 TI - Neurobiology of chronic mild stress: parallels to major depression. AB - The chronic mild (or unpredictable/variable) stress (CMS) model was developed as an animal model of depression more than 20 years ago. The foundation of this model was that following long-term exposure to a series of mild, but unpredictable stressors, animals would develop a state of impaired reward salience that was akin to the anhedonia observed in major depressive disorder. In the time since its inception, this model has also been used for a variety of studies examining neurobiological variables that are associated with depression, despite the fact that this model has never been critically examined to validate that the neurobiological changes induced by CMS are parallel to those documented in depressive disorder. The aim of the current review is to summarize the current state of knowledge regarding the effects of chronic mild stress on neurobiological variables, such as neurochemistry, neurochemical receptor expression and functionality, neurotrophin expression and cellular plasticity. These findings are then compared to those of clinical research examining common variables in populations with depressive disorders to determine if the changes observed following chronic mild stress are in fact consistent with those observed in major depression. We conclude that the chronic mild stress paradigm: (1) evokes an array of neurobiological changes that mirror those seen in depressive disorders and (2) may be a suitable tool to investigate novel systems that could be disturbed in depression, and thus aid in the development of novel targets for the treatment of depression. PMID- 22776774 TI - Flow cytometric analysis of lymphocyte subset kinetics in Bali cattle experimentally infected with Jembrana disease virus. AB - Jembrana disease virus (JDV) is an unusual bovine lentivirus that causes an acute and sometimes fatal disease after a short incubation period in Bali cattle (Bos javanicus). The pathological changes occur primarily in lymphoid tissues, which feature proliferating lymphoblastoid-like cells predominantly throughout parafollicular (T-cell) areas, and atrophy of follicles (B-cell) areas. Five Bali cattle were experimentally infected with JDV and all developed typical clinical signs of Jembrana disease characterised by a transient febrile response, enlargement of superficial lymph nodes and a significant leukopenia. Flow cytometric analysis of PBMC during the acute (febrile) disease phase showed that the reduced number of lymphocytes was due to a significant decrease in both the proportion and absolute numbers of CD4(+) T cells, but not CD8(+) T-cells or CD21(+) B-cells. At the end of the febrile phase, total numbers of both CD8(+) T cells and CD21(+) B-cells increased significantly, while CD4(+) T-cell numbers remained below normal values, resulting in a significantly reduced CD4(+):CD8(+) ratio. We speculate that the persistent depletion of CD4(+) T cells following JDV infection, through lack of CD4(+) T cell help to B cells, may explain the lack of production of JDV-specific antibodies for several weeks after recovery despite an increase in CD21(+) B cell numbers. Further, our previous data showing that IgG(+) plasma cells are targets for JDV infection, correlated with our current data demonstrating an increase in CD8(+) T cell numbers, supports the suggestion that anti-viral cytotoxic T cell or other cell-mediated immune responses may be critical in the recovery process, although this remains to be formally demonstrated for JDV. PMID- 22776775 TI - Facts not fiction: Fake Botox((r)), omega-3 fatty acids are good for you and the "Toxic Tush" syndrome. PMID- 22776776 TI - Man-induced hydrological changes, metazooplankton communities and invasive species in the Berre Lagoon (Mediterranean Sea, France). AB - The Berre Lagoon has been under strong anthropogenic pressure since the early 1950s. The opening of the hydroelectric EDF power plant in 1966 led to large salinity drops. The zooplankton community was mainly composed of two common brackish species: Acartia tonsa and Brachionus plicatilis. Since 2006, European litigation has strongly constrained the input of freshwater, maintaining the salinity above 15. A study was performed between 2008 and 2010 to evaluate how these modifications have impacted the zooplankton community. Our results show that the community is more diverse and contains several coastal marine species (i.e., Centropages typicus, Paracalanus parvus and Acartia clausi). A. tonsa is still present but is less abundant, whereas B. plicatilis has completely disappeared. Strong predatory marine species, such as chaetognaths, the large conspicuous autochtonous jellyfish Aurelia aurita and the invasive ctenophore Mnemiopsis leidyi, are now very common as either seasonal or permanent features of the lagoon. PMID- 22776777 TI - Oxidative stress responses and biological indices in the giant clam Tridacna maxima and the reef fish Epinephelus merra from the French Polynesian Moorea Island. AB - Responses of biological indices and oxidative stress biomarkers were studied in the giant clam Tridacna maxima and in the fish Epinephelus merra collected from two sites differing by their level of contamination in the French Polynesian Moorea island. Higher levels of catalase (CAT), glutathione-S-transferases (GST) and thiobarbituric acid reactive substances (TBARs) were observed in the hepatopancreas of T. maxima and in the liver of E. merra compared to muscle. CAT and TBARs levels were significantly higher in the hepatopancreas of clams collected from the impacted site (Vaiare) compared to the reference site (bay of Cook). The same pattern was observed for TBARs levels in the liver of E. merra. These results indicate that both organisms from the impacted site were exposed to contaminants leading to an oxidative stress and demonstrate, for the first time, the usefulness of T. maxima and E. merra as sentinel species for biomonitoring reef environments. PMID- 22776778 TI - Effect of saxagliptin on the pharmacokinetics of the active components of Ortho Cyclen((r)), a combined oral contraceptive containing ethinyl estradiol and norgestimate, in healthy women. AB - Saxagliptin (OnglyzaTM) is a dipeptidyl peptidase-4 (DPP4) inhibitor for treating type 2 diabetes mellitus. This open-label, randomized, two-way crossover study in 20 healthy female subjects investigated the effect of saxagliptin on the pharmacokinetics (PK) of the active components of a combined oral contraceptive (COC). Subjects received either COC (Ortho-Cyclen((r))) once daily (QD) for 21 days, then 5 mg saxagliptin QD + COC QD for 21 days, or vice versa. Coadministration of saxagliptin and COC did not alter the steady-state PK of the primary active oestrogen (ethinyl estradiol) or progestin (norelgestromin) COC components. The area under the concentration-time curve (AUC) and peak plasma concentration (Cmax) of an active metabolite of norelgestromin (norgestrel) were increased by 13 and 17%, respectively, a magnitude that was not considered clinically meaningful. Coadministration of saxagliptin and COC in this study was generally well-tolerated. Saxagliptin can be co-prescribed with an oestrogen/progestin combination for women taking oral contraceptive. PMID- 22776779 TI - Comparative assessment of two commonly used commercial ELISA tests for the serological diagnosis of contagious agalactia of small ruminants caused by Mycoplasma agalactiae. AB - BACKGROUND: Contagious agalactia (CA) of sheep and goats caused by Mycoplasma agalactiae is a widely occurring economically important disease that is difficult to control. The ELISA is commonly used for the serological detection of CA but it has some limitations and the performance of the available tests have not been properly evaluated.Two commercial ELISA kits are widely used, one involving a fusion protein as target antigen and the other a total antigen. The objectives were to compare these tests by evaluating:i. Their diagnostic sensitivity and specificity, the relevance of the recommended cut-off points, the correlation between the two tests, and, the correlation between serology data and the milk shedding of M. agalatiae;ii. The influence of extrinsic factors such as the targeted animal species, geographical origin of the samples, intra-specific variability of M. agalactiae and concurrent mycoplasma infections.A sample of 5900 animals from 211 farms with continuous CA monitoring for 20 years and no prior vaccination history was used. The infection status was known from prior bacteriological, epidemiological and serological monitoring with a complementary immunoblotting test. RESULTS: The average diagnostic sensitivity was 56% [51.8 59.8] for the fusion protein ELISA and 84% [81.3-87.2] for the total antigen ELISA, with noteworthy flock-related variations. The average diagnostic specificity for the fusion protein ELISA was 100% [99.9-100], and for the total antigen ELISA differed significantly between goats and sheep: 99.3% [97.4-99.9] and 95.7% [93.8-97.2] respectively.Experimental inoculations with different M. agalactiae strains revealed that the ELISA kits poorly detected the antibody response to certain strains. Furthermore, test performances varied according to the host species or geographical origin of the samples.Finally, the correlation between milk shedding of M. agalactiae and the presence of detectable antibodies in the blood was poor. CONCLUSIONS: These serological tests are not interchangeable. The choice of a test will depend on the objectives (early detection of infection or disease control program), on the prevalence of infection and the control protocol used. Given the variety of factors that may influence performance, a preliminary assessment of the test in a given situation is recommended prior to widespread use. PMID- 22776780 TI - Type-1 cannabinoid receptor signaling in neuronal development. AB - The type-1 cannabinoid receptor (CB1R) was initially identified as the neuronal target of Delta(9)-tetrahydrocannabinol (THC), the major psychoactive substance of marijuana. This receptor is one of the most abundant G-protein-coupled receptors in the adult brain, the target of endocannabinoid ligands and a well characterized retrograde synaptic regulator. However, CB1Rs are also highly and often transiently expressed in neuronal populations in the embryonic and early postnatal brain, even before the formation of synapses. This suggests important physiological roles for CB1Rs during neuronal development. Several recent reviews have summarized our knowledge about the role of the endocannabinoid (eCB) system in neurodevelopment and neurotransmission by focusing on the metabolism of endocannabinoid molecules. Here, we review current knowledge about the effects of the modulation of CB1R signaling during the different phases of brain development. More precisely, we focus on reports that directly implicate CB1Rs during progenitor cell migration and differentiation, neurite outgrowth, axonal pathfinding and synaptogenesis. Based on theoretical considerations and on the reviewed experimental data, we propose a new model to explain the diversity of experimental findings on eCB signaling on neurite growth and axonal pathfinding. In our model, cell-autonomus and paracrine eCBs acting on CB1Rs are part of a global inhibitory network of cytoskeletal effectors, which act in concert with positive-feedback local-excitation loops, to ultimately yield highly polarized neurons. PMID- 22776781 TI - Psychosocial impact on anophthalmic patients wearing ocular prosthesis. AB - The aim of this study was to assess the improvement in psychosocial awareness of anophthalmic patients wearing ocular prostheses and its relationship with demographic characteristics, factors of loss/treatment, social activity, and relationship between professional and patient. Surveys including a form for evaluation of psychosocial pattern were conducted with 40 anophthalmic patients rehabilitated with ocular prosthesis at the Center of Oral Oncology in the authors' dental school from January 1998 to November 2010. The improvement in psychosocial awareness was assessed by comparing the perception of some feelings reported in the period of eye loss and currently. Wilcoxon tests were applied for comparison of patients' perception between the periods. chi(2) tests were used to assess the relationship between the improvement in psychosocial awareness and the variables of the study. In addition, the logistic regression model measured this relationship with the measure of odds ratio. The feelings of shame, shyness, preoccupation with hiding it, sadness, insecurity and fear were significant for improvement in psychosocial awareness. It was concluded that the anophthalmic patients wearing an ocular prosthesis has significant improvement in psychosocial awareness after rehabilitation. PMID- 22776782 TI - Phosphate mass removal during hemodialysis: a comparison between eKT/V-matched conventional and extended dialysis. AB - BACKGROUND AND OBJECTIVES: The control of hyperphosphatemia is an unmet need in dialysis care. Compared to conventional hemodialysis (cHD), extended hemodialysis (eHD) appears to more easily control blood phosphate levels in chronically dialyzed patients. Here, we sought to compare eKT/V-matched cHD and eHD procedures in order to quantify the contribution of dialysis prescription and time in the mass removal of phosphate. METHODS: Eight stable hemodialysis patients with negligible residual renal function underwent cHD and eHD sessions adjusted to provide the same eKT/V(urea). Total dialysate, total and hourly partial dialysate and blood samples were collected for comparison of mass extraction of urea, creatinine, and phosphate. RESULTS: Mean eKT/V(urea) was similar in eHD and cHD (1.30 vs. 1.28, p = nonsignificant). Likewise, mass removal of urea and creatinine during cHD and eHD were not significantly different. Conversely, phosphate mass removal was 40% higher with eHD as compared to cHD (1,219 +/- 262 vs. 858 +/- 186 mg, p = 0.015). Although hourly mass removal of phosphate was higher during cHD, the prolonged period of lesser but continuous removal was responsible for higher total phosphate elimination during eHD. CONCLUSION: In dialysis sessions matched to provide a similar eKT/V(urea), removal of phosphate increases by 40% when time is extended from 4 to 8 h. Urea based adequacy models cannot be used to predict the amount of phosphorus removal during hemodialysis. PMID- 22776783 TI - Evidence-Based Laboratory Medicine (EBLM) in autoimmunity. PMID- 22776784 TI - Diagnostic accuracy and predictive value of extended autoantibody profile in systemic sclerosis. AB - Systemic sclerosis (SSc) is a heterogeneous autoimmune disorder characterized by microvascular injury, fibrosis of the skin and other organs, and presence of antinuclear autoantibodies (ANA) with a prevalence varying from 80 to 98%. The ANA classically detected in SSc include anti-centromere (ACA) and anti topoisomerase I (ATA), which are positive in 50-60% of the patients. Even if other autoantibodies, such as anti-fibrillarin (AFA), anti-RNA polymerase III (RNAP III), anti-PMScl, anti-Th/To, and anti-hUF/NOR-90, are almost specific for SSc, until recently they were not routinely looked for, since the techniques for their identification were not suitable for routine use. In recent years, the advances in the knowledge of the biochemistry and of the immunoreactive sites of the autoantigens led to the development of new immunoassays using recombinant proteins as autoantigens. We evaluated a new multiplex line immunoblot assay (LIA) for the simultaneous detection of 13 different SSc-associated autoantibodies, in a cohort of 210 SSc Italian patients. The sensitivity and the specificity of this assay were as follows: 30.5% and 97.3% for ACA (anti-CENP-B), 29.5% and 96% for ACA (anti-CENP-A), 20% and 99.3% for ATA, 5.7% and 99.3% for anti-RNAP III (RP-155), 5.2% and 100% for anti-RNP III (RP-11), 6.7% and 98% for anti-PMScl (PMScl-100), 10.9% and 93.3% for anti-PMScl (PMscl-75), 3.3% and 98.7% for anti-Th/To, 0.48% and 100% for AFA, 4.8% and 96.7% for anti-hUF/NOR-90, 4.7% and 96% for anti-Ku, 0.95% and 100% for anti-Platelet-Derived Growth Factor Receptor, and 18.1% and 50% for anti-Ro-52, respectively. These results, which are similar to those obtained in other studies using traditional techniques, show that the LIA assay can be considered a more rapid and a more practical method than immunoprecipitation assays for studying SSc-related antibodies in the diagnostic work-up of SSc patients. PMID- 22776785 TI - Exercise as a therapeutic tool to counteract inflammation and clinical symptoms in autoimmune rheumatic diseases. AB - Chronic inflammation is a common feature shared by several autoimmune rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathies, systemic sclerosis, and ankylosing spondylitis. Therefore, blocking or reducing inflammation is one of the major treatment strategies in these diseases. In this context, exercise training has emerged as a potential therapeutic tool in counteracting systemic inflammation, thereby leading to better clinical outcomes. The aims of this review are i) to provide a summary of the clinical effects of exercise training in selected autoimmune rheumatic diseases; and ii) to discuss the potential anti-inflammatory role of exercise training in autoimmune rheumatic diseases, stressing the gaps in literature and the clinical and scientific perspectives in the field. PMID- 22776786 TI - TSH receptor autoantibody immunoassay in patients with Graves' disease: improvement of diagnostic accuracy over different generations of methods. Systematic review and meta-analysis. AB - BACKGROUND: TSH receptor antibodies (TRAb) are the diagnostic hallmark of Graves' disease (GD) and immunoassays for their detection have been available for more than 30 years over three generations of laboratory methods. Despite a growing body of data produced by clinical and laboratory research which demonstrates its elevated sensitivity and specificity, TRAb testing is poorly used for diagnosing GD. The aim of our systematic review and meta-analysis is to verify the diagnostic performance of TRAb detected with 2nd and 3rd generation immunoassay methods. METHODS: We searched for English articles using MEDLINE with the search terms "TSH receptor antibody assay", "TSH Receptor antibody tests" and "Graves' disease". We analyzed studies reporting on TSH receptor antibody tests performed by quantitative immunoassays, on untreated patients with GD as the index disease (sensitivity) and on a control group of either healthy subjects or patients affected by other thyroid diseases (specificity). A total of 681 titles were initially identified with the search strategy described. 560 publications were excluded based on abstract and title. Full-text review was undertaken as the next step on 111 publications providing data on TRAb testing; 58 articles were subsequently excluded because they did not include untreated GD patients, or used either bioassays or 1st generation immunoassays. 32 were also excluded because they included data only on sensitivity or only on specificity of the assay, or were duplicates. Finally, 21 articles were selected for meta-analysis. Extraction of data from selected articles was performed by two authors independently, using predefined criteria: the number of patients with GD and the number of healthy or diseased controls; specification of the analytical method used to detect TRAb; sensitivity and specificity of the assay. RESULTS: The meta-analysis showed that the overall pooled sensitivity and specificity of the 2nd and 3rd generation TRAb assays are 97.1% and 97.4%, and 98.3% and 99.2%, respectively, with little difference between the types of immunoassay methods employed (human or porcine receptor, manual or automated procedure). The likelihood of a TRAb-positive individual to have GD is 1367- to 3420-fold greater (depending upon the type of assay) compared to a TRAb-negative person. CONCLUSIONS: Data from the meta analysis showed that TRAb measured with 2nd and 3rd generation immunoassay methods have very high sensitivity and specificity in the diagnosis of GD. The difference between 2nd and 3rd generation methods is small and is equally useful. In contrast with recommendations made by clinical endocrinologists who are not familiar with the state of the art in diagnostic technologies of autoimmunology laboratories, we propose a wide application of these tests in clinical practice to screen all hyperthyroid patients. PMID- 22776787 TI - Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. AB - OBJECTIVE: To evaluate whether vitamin D levels are related to the risk of developing autoimmune diseases and whether supplementation with vitamin D can modify the course of the diseases. METHODS: We reviewed the most relevant papers published from January 1973 to October 2011, using Medline and EMBASE and the search terms "vitamin D"; "autoimmune disease"; "autoimmunity"; "rheumatoid arthritis"; "systemic lupus erythematosus"; "scleroderma"; "systemic sclerosis"; "type 1 diabetes"; "multiple sclerosis"; and "undifferentiated connective tissue disease". We selected studies on the environmental, genetic and epidemiologic association of vitamin D with autoimmune diseases. Using the strategy described, we identified 1268 articles. 331 articles were eliminated on the basis of the title and another 703 on the basis of the abstract, since they were considered irrelevant for the purposes of the study. Full-text examination was performed on the remaining 234 studies, and a further 15 studies were excluded from the review, since the results had been confirmed or superseded by more recent research. Finally, a systematic review was conducted on 219 articles concerning cross-sectional data on: vitamin D levels and autoimmune diseases; interventional data on vitamin D supplementation in autoimmune diseases; prospective data linking vitamin D level or intake to autoimmune disease risk. RESULTS: Physiopathology studies confirm that hypovitaminosis D, in genetically predisposed subjects, can impair self tolerance by compromising the regulation of dendritic cells, of regulatory T-lymphocytes and of Th1 cells. Cross-sectional studies show that levels of vitamin D <30 ng/mL are present in a significant percentage, not only in patients with autoimmune disease, but also in healthy subjects (30-77%), and link profound deficiency (<10 ng/mL) with aggravation of symptomatology, while genetic studies associate polymorphism of vitamin D receptors to various autoimmune diseases. Among experimental studies on humans, only those on type-1 diabetes prove that the risks are significantly reduced in infants treated with vitamin D after the 7th month (OR 0.71, 95% CI, 0.60 to 0.84) and that a dose-response effect exists. CONCLUSIONS: Basic, genetic, and epidemiological studies indicate a potential role of vitamin D in the prevention of autoimmune diseases, but randomized and controlled trials are necessary to establish the clinical efficacy of vitamin D supplementation in ill or at-risk subjects. PMID- 22776788 TI - Asymptomatic synchronous quintuple primary cancers. AB - We encountered a 46-year-old woman with synchronous quintuple primary cancers. She did not present with any symptoms, and her tumors were discovered at a gynecological screening. She had clear cell adenocarcinoma of the right ovary, moderately differentiated endometrioid adenocarcinoma of the endometrium, moderately differentiated adenocarcinoma of the ascending colon, well differentiated adenocarcinoma of the rectum, and poorly differentiated papillary adenocarcinoma of the left lung. A fluorodeoxyglucose-positron emission tomography and other imaging techniques were extremely useful for the diagnosis of multiple primary cancers. Moreover, MSH2 protein expression was absent in the tumors of the ovary, endometrium, ascending colon, and rectum, while the rectal cancer also lacked MLH1 protein. These findings suggested that an abnormality of DNA mismatch repair genes was responsible for carcinogenesis. PMID- 22776789 TI - Objectives and applications of phenotyping network set-up for livestock. AB - Providing phenotypic information, which is accurate, reliable, repeatable and comparable across countries or laboratories, is critical to gain a better understanding of the relationship between genes and phenotypes. So far, it is indeed extremely difficult to combine different sources of phenotypic data from multiple origins, partly because of the variability in the methods of phenotyping. The phenotyping program of livestock involves the definition of complex phenotypes obtained from data integration at different levels (from molecules to herds), the implementation of the latest technologies to accurately characterize at high speed and low cost, the greatest number of animals in a better characterized environment, and the development and sharing of large databases for data analysis and modeling. Such a program also involves the construction of a coordinated network of research and professional facilities and a common language with shared definition of unambiguous animal traits and of methods to assess them. To this end, it will build on the 'Animal Trait Ontology of Livestock' (ATOL) project with the objective of defining precisely the phenotypes of interest for farm animals. Then, it will be necessary to combine an environmental information system related to animal husbandry and associated methods to capture the phenotypic differences between animals. PMID- 22776790 TI - Effect of estrus synchronization treatment after luteolysis on Holstein heifers as embryo transfer recipients. AB - This study was designed to evaluate the effect of estrus synchronization treatments on recipient heifers for embryo transfer (ET). Holstein heifers were separated into the following three groups: (i) an administration of 50 ug GnRH (gonadotropin-releasing hormone) analog was given to heifers at a random stage of the estrus cycle, followed 7 days later by two administrations of 7.5 mg prostaglandin F2 alfa analog (PG) as control; (ii) another administration of 100 ug GnRH was given to the control group at 48 h after the administration of PG as the second GnRH group; and (iii) an administration of 0.75 mg estradiol benzoate (E2) was given to the control group at 24 h after the administration of PG as the E2 group. Each method caused estrus synchronization. Fresh embryos were nonsurgically transferred into the suitable recipients that had a functional corpora lutea (CL) 7 days after estrus. The E2 group showed a significantly higher (P < 0.01) rate of estrus synchronization (98.9%) at 1-3 days after PG administration and the final pregnancy rate of the E2 group (50.6%) was also significantly higher than the other groups (37.1%, P < 0.05 and 30.9%, P < 0.01, respectively). These findings demonstrate that E2 administration 24 h after PG protocol is effective for estrus synchronization of Holstein heifers, thus improving the productivity of ET. PMID- 22776791 TI - Immunolocalization of steroidogenic enzymes and their expression during the breeding season in the testes of wild raccoon dogs (Nyctereutes procyonoides). AB - The objective of this study was to investigate immunolocalization of steroidogenic enzymes 3betaHSD, P450c17 and P450arom and their expression during the breeding season in wild male raccoon dogs. The testicular weight, size and seminiferous tubule diameters were measured, and histological and immunohistochemical observations of testes were performed. The messenger RNA expression (mRNA) of 3betaHSD, P450c17 and P450arom was measured in the testes during the breeding season. 3betaHSD was found in Leydig cells during the breeding and non-breeding seasons with more intense staining in the breeding season. P450c17 was identified in Leydig cells and spermatids in the breeding season, whereas it was present only in Leydig cells in the non-breeding season. The localization of P450arom changed seasonally: no immunostaining in the non breeding season; more extensive immunostaining in Leydig cells, Sertoli cells and elongating spermatids in the breeding season. In addition, 3betaHSD, P450c17 and P450arom mRNA were also expressed in the testes during the breeding season. These results suggested that seasonal changes in testicular weight, size and seminiferous tubule diameter in the wild raccoon dog were correlated with spermatogenesis and immunoreactivity of steroidogenic enzymes and that steroidogenic enzymes may play an important role in the spermatogenesis and testicular recrudescence and regression process. PMID- 22776792 TI - Effect of iodine, selenium and cobalt rumen boluses given to dry dairy cows on the immunoglobulin and thyroid hormone status of calves. AB - The objective was to determine the effect of rumen boluses containing 6800 mg iodine, 1000 mg selenium and 1000 mg cobalt given to dry dairy cows on the efficiency of colostral immunoglobulin G (IgG) absorption in calves. Thirteen cows received the bolus approximately 58 days before calving. A further 12 cows received no bolus and were used as controls. The cows were housed as one group. Calves were prevented from suckling for the first 24 h of life, and were given three feeds of a fixed quantity of colostrum. At 24 h, the average plasma concentrations of IgG in the calves were 15.5 and 13.4 g/L for the control and bolus groups, respectively; these were not significantly different (P = 0.212). Bolus treatment was associated with higher levels of free and total tri iodothyronine (T3) and thyroxine (T4) in the dams (all P < 0.001), although it had no effect on thyroid hormone levels in the calves. There were nevertheless positive and negative relationships between the efficiency with which colostral IgG was absorbed at 24 h and, respectively, total T3 at 24 h (P < 0.05) and total T4 at 1 h of age (P < 0.05). The underlying basis for these relationships remains to be established. PMID- 22776793 TI - Differences in adipose tissue inflammation and oxidative status in C57BL/6 and ApoE-/- mice fed high fat diet. AB - Apolipoprotein E deficient (Apo E-/-) mice are more resistant to the development of obesity compared to C57BL/6 wild type mice. They also hold a high basal oxidative status due to the loss of antioxidant action of apolipoprotein E. Since obesity is also an inducer of inflammation, we studied the effect of high-fat diet on obesity and oxidative stress in C57BL/6 and Apo E-/- mice for 9 weeks. The results confirmed that Apo E-/- mice fed high-fat diet are more resistant to the increase of both body weight and adiposity compared to C57BL/6 mice. Despite this, Apo E-/- mice presented a higher basal oxidative stress that was enhanced by high-fat diet. Macrophage infiltration, macrophage forming crown-like structures and proinflammatory adipokines (interleukin 6 and tumor necrosis factor alpha) were all higher in adipose tissue from Apo E-/- compared to C57BL/6 mice, regardless of diet type. In conclusion, although Apo E-/- mice are more resistant to becoming obese, they develop more severe adipose tissue inflammation companied by its consequences. PMID- 22776794 TI - Regional and circadian variations of sweating rate and body surface temperature in camels (Camelus dromedarius). AB - It was the aim of this study to investigate the regional variations in surface temperature and sweating rate and to visualize body thermal windows responsible for the dissipation of excess body heat in dromedary camels. This study was conducted on five dromedary camels with mean body weight of 450 +/- 20.5 kg and 2 years of age. Sweating rate, skin and body surface temperature showed significant (P < 0.001) circadian variation together with the variation in ambient temperature. However, daily mean values of sweating rate, skin and body surface temperature measured on seven regions of the camel body did not significantly differ. The variation in body surface temperature compared to the variation in skin temperature was higher in the hump compared to the axillary and flank regions, indicating the significance of camel's fur in protecting the skin from daily variation in ambient temperature. Infrared thermography revealed that flank and axillary regions had lower thermal gradients at higher ambient temperature (T(a) ) and higher thermal gradients at lower T(a) , which might indicate the working of flank and axillary regions as thermal windows dissipating heat during the night. Sweating rate showed moderate correlation to skin and body surface temperatures, which might indicate their working as potential thermal drivers of sweating in camels. PMID- 22776795 TI - Effects of daily management changes on behavioral patterns of a solitary female African elephant (Loxodonta africana) in a zoo. AB - This study investigated the effects of changes in daily management on behavior of a solitary female elephant in a zoo. The activity budget and space utilization of the subject and the management changes were recorded for 1 year after the conspecific male died. The observation days could be categorized into five clusters (C1-C5) by the characteristic behavioral pattern of each day. C1 had the highest percentage of resting of all clusters, and was observed after the loss of the conspecific and the beginning of use of the indoor exhibition room at night. C2, which had the highest percentage of stereotypy of any cluster, was observed after the beginning of habituation to the indoor exhibition room. Also, when the time schedule of management was changed irregularly, the subject frequently exhibited stereotypic pacing (C2, C4). The subject tended to rest when exhibiting lameness in the left hind limb (C3). In C5, activity reached a high level when she could utilize a familiar place under a stable management schedule. These results indicate that management changes affected the mental stability of an elephant in the early stage of social isolation. PMID- 22776796 TI - Ammonia-oxidizing Archaea in laboratory-scale activated sludge systems for wastewater of low- or high-ammonium concentration. AB - Ammonia-oxidizing bacteria (AOB) is known as ammonia-oxidizer in wastewater treatment systems. However, ammonia-oxidizing Archaea (AOA) is found from various environments, including wastewater treatment systems. In this study, to investigate the relationships between AOA population and ammonia concentration, AOA was monitored in two laboratory-scale reactors treating artificial wastewater of different ammonium concentrations by denaturing gradient gel electrophoresis targeting ammonia monooxygenase genes. At day 60 of the operation, AOA populations dominant in each reactor differed, suggesting the importance of influent ammonia concentration in dominant AOA selection. PMID- 22776797 TI - The cure fraction of glioblastoma multiforme. AB - BACKGROUND AND PURPOSE: This study presents a statistical model to explore the presence of a population-based cure fraction in populations with a GBM. PATIENTS AND METHODS: Data for this study was obtained from the Surveillance, Epidemiology and End-Results (SEER) database. Relative survival measures were modelled using non-mixture cure fraction models. RESULTS: The extraction and subsequent period modeling of the dataset resulted in a final total of 11,189 patients and a total of 10,289 years of patient follow-up (between 2001 and 2006). The cure fraction of young adults is expected to be 12% (95% CI 7-16), which is estimated to occur at a minimum time of 10 years post diagnosis. INTERPRETATION: The data, using population-based cure fraction models, indicate that a possibility for cure appears to be present in the young adult population, and occurs at 10 years after diagnosis. Because of the biological and statistical features of this patient population, it is appropriate to study GBM populations using cure fraction models. PMID- 22776798 TI - Descriptive epidemiology of pediatric intracranial neoplasms in Egypt. AB - OBJECTIVE: The characteristics of 451 Egyptian children (aged 0-14 years) with primary intracranial neoplasms were investigated for demographic, clinical, topographical and pathological features using the most recent 2007 Classification of Central Nervous System Tumors. PATIENTS AND METHODS: This was a retrospective study performed in the Departments of Pediatric Neurosurgery of the Cairo University Hospitals from 2005 to 2008. RESULTS: There was a slight male predominance (51.4%) observed in our study, and the most affected age group was 5 9 years old (43.2%). Most of the tumors were confined to a single compartment (infratentorial in 49.7%, supratentorial in 46.6%), while 3.8% of the tumors involved multiple compartments. The most common intracranial tumors were astrocytomas (35%), medulloblastomas (18.8%), craniopharyngiomas (11.3%) and ependymomas (10%). Pilocytic astrocytomas constituted 55% of all astrocytomas and 19.3% of all brain tumors, only slightly ahead of medulloblastomas. Less common types were primitive neuroectodermal tumors (2.7%), followed by meningiomas, germ cell tumors and choroid plexus tumors (2.4% each). According to the International Classification of Diseases for Oncology Coding (ICD-O-4), benign, borderline and malignant tumors constituted 7.54, 36.14 and 56.32%, respectively. CONCLUSION: The characteristics of pediatric intracranial tumors in Egypt are generally similar to those reported in the literature, with only minor differences. PMID- 22776800 TI - Beyond waist circumference in an adult male population of Southern Italy: Is there any role for subscapular skinfold thickness in the relationship between insulin-like growth factor-I system and metabolic parameters? AB - BACKGROUND: Apart from waist circumference, other adiposity measures, such as subscapular skin fold (SST), arouse growing interest due to their relationship to metabolic complications and cardiovascular risk. The IGF-I system is deregulated in obese subjects in proportion to their degree of visceral adiposity. AIM: To examine the association among IGF-I, IGF-binding protein (BP)-1 and -3 levels and different measures of adiposity in a sample of adult male population in Southern Italy. MATERIALS AND METHODS: A complete database for this analysis was available for 229 (age range 50-82 yr) participating at 2002-2004 Olivetti Heart Study follow-up. RESULTS: After adjustment for age, IGF-I was inversely associated with body mass index (BMI) and waist circumference (p<0.05). IGFBP-1 was inversely associated with BMI, waist circumference, SST, homeostasis model assessment (HOMA) index, fat mass. HOMA index, age, and SST significantly predicted the IGFBP-1 plasma levels, with 24% of IGFBP-1 variability explained at a linear regression analysis. CONCLUSIONS: IGFBP-1 inversely correlated to adiposity and HOMA index. Among adiposity indexes, SST was the best predictor of IGFBP-1 levels. The evaluation of some components of the IGF system, and simple measures of body adiposity, such as SST, may represent a further tool to better evidence phenotype profiles associated to the pathogenetic mechanism of cardiovascular risk factor clustering in male adults. PMID- 22776801 TI - Ultrastructural analysis of vascular features in cerebral cavernous malformations. AB - OBJECTIVE: Investigation of the structure of vascular malformations highlights the pathogenic mechanisms underlying their clinical behavior. One of the vascular malformations is called cerebral cavernous malformation (CCM). However, the ultrastructural features of the vascular malformations are not defined in detail. METHODS: We aimed to investigate the ultrastructural features of CCMs using transmission (TEM), scanning (SEM) electron microscopy, and also immunohistochemistry methods with antibodies against CCM proteins such as CCM2 and CCM3. CCM tissues (n=6) microsurgically excised from patients for conventional indications. RESULTS: CCM2 and CCM3 were strongly detected in the vascular endothelium. However, there was a very weak immunostaining in stroma. SEM observations revealed that there were ruptures and damages in the luminal endothelium, possibly due to the damage of intercellular junctions. TEM observations also showed a few ruptures and detachments between the endothelium and basal lamina as observed with partially damages and disconnections. The architecture of pericytes showed protrusions and shrinkages. Our results suggest that the thin vessel walls of CCMs were lacking of subendothelial support and intact basal lamina underlying the endothelial cells. CONCLUSION: This study is so far the first study attempting to show human CCM lesions with SEM. We believe that an understanding of the ultrastructural features of these lesions by light and electron microscopy techniques would help to understand the pathology of these diseases. PMID- 22776802 TI - Transsphenoidal removal of huge pituitary adenomas with marked suprasellar extension: results with modified surgical technique. AB - OBJECTIVE: A modified transsphenoidal technique to remove huge pituitary adenomas with marked suprasellar extension (4.5-8 cm of maximum diameter) is presented. METHODS: The technique allowed to avoid the occurrence of a precocious descent of the suprasellar cisternal plane into the sellar plane during tumour removal and its related consequences (incomplete tumour removal, occurrence of cerebrospinal fluid leak, prolonged time of postoperative stay in hospital). Technique is performed opening at the beginning only the lateral parts of peritumoral dura mater, leaving the central part of the dura mater in support of the central part of tumour and suprasellar cisternal plane. After removal of lateral parts of the tumour, the central part of peritumoral dura mater is opened and the central intra- and supra-sellar parts of the tumour are removed. RESULTS: Total removal was accomplished in 64% and 45% in groups two and one respectively. Intraoperative CSF leak occurred in 2.4% and 22.5% respectively in groups two and one. Postoperative CSF fistula did not occur in group two, while it occurred in 7.4% of patients of group one. Average time of postoperative stay in hospital was 4.3 and 8.2 days in groups two and one respectively. CONCLUSION: The presented modified transsphenoidal microsurgical technique for removal of huge pituitary adenomas allowed to achieve better results than patients operated by standard transsphenoidal surgery. PMID- 22776803 TI - Methods for the practical determination of the mechanical strength of tablets- from empiricism to science. AB - This review aims to awake an interest in the determination of the tensile strength of tablets of various shapes using a variety of direct and indirect test methods. The United States Pharmacopoeia monograph 1217 (USP35/NF30, 2011) has provided a very good approach to the experimental determination of and standards for the mechanical strength of tablets. Building on this monograph, it is hoped that the detailed account of the various methods provided in this review will encourage industrial and academic scientists involved in the development and manufacture of tablet formulations to take a step forward and determine the tensile strength of tablets, even if these are not simply flat disc-shaped or rectangular. To date there are a considerable number of valid test configurations and stress equations available, catering for many of the various shapes of tablets on the market. The determination of the tensile strength of tablets should hence replace the sole determination of a breaking force, because tensile strength values are more comparable and suggestions for minimum and/or maximum values are available. The review also identifies the gaps that require urgent filling. There is also a need for further analysis using, for example, Finite Element Method, to provide correct stress solutions for tablets of differing shapes, but this also requires practical experiments to find the best loading conditions, and theoretical stress solutions should be verified with practical experiments. PMID- 22776804 TI - Sarcoptic-mange detector dogs used to identify infected animals during outbreaks in wildlife. AB - BACKGROUND: One of the main aims of forensic investigation is the detection and location of people and substances of interest, such as missing people and illegal drugs. Dogs (Canis lupus var. familiaris) have had an important role in legal and forensic investigations for decades; nonetheless canines' keen sense of smell has never been utilized in either the surveillance or control of wildlife diseases. The rapid removal and treatment of infected carcasses and/or sick animals is a key task in the management of infectious diseases, but it is usually difficult or impractical to carry out in the wild. RESULTS: In this paper we report on a study running over a period of 15 years, in which - for the first time to our knowledge - two disease-detector dogs were trained to follow the scent of Sarcoptes infected animals and to find carcasses, even under the snow, and apparently no false positives were detected in fieldwork. Sarcoptic mange-detector dogs were used to collect the carcasses of 292 mangy wild animals and to identify, separate from their herd, and capture 63 mange-infected wild animals in the Italian Alps. CONCLUSIONS: Properly trained disease-detector dogs are an efficient and straightforward tool for surveillance and control of sarcoptic mange in affected wild animal populations. PMID- 22776805 TI - Health effects of occupational exposure in a dairy food industry, with a specific assessment of exposure to airborne lactic acid bacteria. AB - OBJECTIVE: Lactic acid bacteria (LAB) are used in food industries as probiotic agents. The aim of this study is to assess the potential health effects of airborne exposure to a mix of preblend (LAB and carbohydrate) and milk powder in workers. METHODS: A medical questionnaire, lung function tests, and immunologic tests were carried out on 50 workers. Occupational exposure to inhalable dust and airborne LAB was measured. RESULTS: Workers not using respiratory masks reported more symptoms of irritation than workers using protection. Workers from areas with higher levels of airborne LAB reported the most health symptoms and the immune responses of workers to LAB was higher than the immune responses of a control population. CONCLUSIONS: Measures to reduce exposure to airborne LAB and milk powder in food industries are recommended. PMID- 22776807 TI - Analysis of ethnic disparities in workers' compensation claims using data linkage. AB - OBJECTIVE: The overall goal of this research project was to assess ethnic disparities in monetary compensation among construction workers injured on the job through the linkage of medical records and workers' compensation data. METHODS: Probabilistic linkage of medical records with workers' compensation claim data. RESULTS: In the final multivariable robust regression model, compensation was $5824 higher (P = 0.030; 95% confidence interval: 551 to 11,097) for white non-Hispanic workers than for other ethnic groups when controlling for injury severity, affected body region, type of injury, average weekly wage, weeks of temporary total disability, percent permanent partial disability, death, or attorney use. CONCLUSIONS: The analysis indicates that white non-Hispanic construction workers are awarded higher monetary settlements despite the observation that for specific injuries the mean temporary total disability and permanent partial disability were equivalent to or lower than those in Hispanic and black construction workers. PMID- 22776806 TI - Developing alternative methods for determining the incidence, prevalence, and cost burden of coronary heart disease in a corporate population. AB - OBJECTIVE: To determine the most appropriate methods for estimating the prevalence and incidence of coronary heart disease (CHD), the associated risk factors, and health care costs in a corporate setting. METHODS: Using medical insurance claims data for the period of 2005-2009 from 18 companies in the Thomson Reuters MarketScan reg database, we evaluated three alternative methods. RESULTS: Prevalence of CHD ranged from 2.1% to 4.0% using a method requiring a second confirmatory claim. Annual incidence of CHD ranged from 1.0% to 1.6% using a method requiring 320 days of benefits enrollment in the previous year, and one claim for a diagnosis of CHD. CONCLUSION: Alternative methods for determining the epidemiologic and cost burden of CHD using insurance claims data were explored. These methods can inform organizations that want to quantify the health and cost burden of various diseases common among an employed population. PMID- 22776808 TI - The effects of workplace occupational mental health and related activities on psychological distress among workers: a multilevel cross-sectional analysis. AB - OBJECTIVE: To investigate the association of workplace occupational mental health (OMH) and related activities with psychological distress of workers in Japan. METHODS: A total of 121 workplaces and their 3540 workers were surveyed using questionnaires assessing selected workplace OMH activities, demographic characteristics, psychological distress, and psychosocial work environment of the workers. A multilevel analysis was conducted. RESULTS: Promotion of communication correlated significantly and negatively with psychological distress among workers after adjusting for the covariates (P < 0.01). Occupational mental health activities correlated marginally significantly and negatively with psychological distress (P = 0.06). Their moderating effect for the worker-level association between psychosocial work environment and psychological distress was not significant. CONCLUSIONS: The findings suggest that promotion of communication in the workplace is associated with reduced psychological distress among workers. In addition, OMH activities may also be useful in reducing psychological distress. PMID- 22776809 TI - Speech perception and production in children with inner ear malformations after cochlear implantation. AB - OBJECTIVE: The aim of this study was to assess the speech perception and speech intelligibility outcome after cochlear implantation in children with malformed inner ear and to compare them with a group of congenitally deaf children implantees without inner ear malformation. METHODS: Six deaf children (five boys and one girl) with inner ear malformations who were implanted and followed in our clinic were included. These children were matched with six implanted children with normal cochlea for age at implantation and duration of cochlear implant use. All subjects were tested with the internationally used battery tests of listening progress profile (LiP), capacity of auditory performance (CAP), and speech intelligibility rating (SIR). A closed and open set word perception test adapted to the Modern Greek language was also used. In the dysplastic group, two children suffered from CHARGE syndrome, another two from mental retardation, and two children grew up in bilingual homes. RESULTS: At least two years after switch-on, the dysplastic group scored mean LiP 62%, CAP 3.8, SIR 2.1, closed-set 61%, and open-set 49%. The children without inner ear dysplasia achieved significantly better scores, except for CAP which this difference was marginally statistically significant (p=0.009 for LiP, p=0.080 for CAP, p=0.041 for SIR, p=0.011 for closed-set, and p=0.006 for open-set tests). CONCLUSION: All of the implanted children with malformed inner ear showed benefit of auditory perception and speech production. However, the children with inner ear malformation performed less well compared with the children without inner ear dysplasia. This was possibly due to the high proportion of disabilities detected in the dysplastic group, such as CHARGE syndrome and mental retardation. Bilingualism could also be considered as a factor which possibly affects the outcome of implanted children. Therefore, children with malformed inner ear should be preoperatively evaluated for cognitive and developmental delay. In this case, counseling for the parents is mandatory in order to explain the possible impact of the diagnosed disabilities on performance and habilitation. PMID- 22776810 TI - Vasoconstrictive and analgesic efficacy of locally infiltrated levobupivacaine in tonsillectomy patients. AB - OBJECTIVES: The use of preincisional plain levobupivacaine, lidocaine adrenaline and saline for perioperative blood loss and postoperative analgesia in pediatric tonsillectomy patients are compared. METHODS: Ninety patients were randomly assigned into one of the 3 groups to receive preincisional peritonsillar infiltration of levobupivacaine 0.25% (group LB), lidocaine-adrenaline 1% with 1:200,000 (group LA) and saline (group S) under general anesthesia. Intraoperative blood loss, pre- and postoperative hemoglobin (hb) and haematocrit (htc) values, hemostasis time, operation duration, number of cautery used (20 W, 1s) and heart rates were recorded. Pain scores in PACU, at 6th, 12th and 24th hours postoperatively and the number of the patients requiring analgesic treatment for first 24h was also recorded. RESULTS: There was a 30% reduction in perioperative blood loss in group LB and 63% reduction in group LA compared to group S (39 +/- 6, 21 +/- 4 and 55 +/- 7 ml respectively) (p<0.001). Even though all three groups have significantly lower postoperative hb and htc values with respect to preoperative levels both local anesthetic groups had significantly higher postoperative hb and htc values than saline (p<0.001). Time required for hemostasis, the number of cautery used for haemostasis and operation duration were lower in groups LB and LA with respect to group S. Pain scores of the group LB revealed a significantly lower score throughout 24h. Only 14 patients in group LB demanded additional analgesic where as all patients in the other groups had. Adding adrenaline to the local anesthetic solution showed no side effects. Also we did not happened to see any complications related to local anesthetic injections. There was no postoperative major bleeding in groups. CONCLUSION: Levobupivacaine has a vasoconstrictive effect in 0.25% concentrations that may be beneficial in tonsillectomy patients and has a consistent analgesic effect. PMID- 22776811 TI - A simple law governing coupled magnetic orders in perovskites. AB - An energetic expression containing four different macroscopic terms is proposed to explain and understand coupled magnetic orders (and the directions of the simultaneously occurring ferromagnetic and/or antiferromagnetic vectors) in terms of anti-phase and/or in-phase tilting of oxygen octahedra in magnetic and multiferroic perovskites. This expression is derived from a suggested simple microscopic formula, and has its roots in the Dzyaloshinsky-Moriya interaction. Comparison with data available in the literature and with first-principles calculations we conduct here confirms the validity of such a simple and general law for any tested structural paraelectric and even ferroelectric phase, and for any chosen direction of any selected primary magnetic vector. PMID- 22776813 TI - Prevalence of bone marrow necrosis in Egyptian cancer patients referring to the National Cancer Institute. AB - BACKGROUND: Bone marrow necrosis is a relatively rare entity which has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders and severe infections. METHODS: The study comprised examination of 5043 bone marrow biopsy specimens performed at the National Cancer Institute, Cairo University, over 7 years period (March 2004-March 2011). It included 5 years retrospective (2867 archived samples) and 2 years prospective (2176 samples). RESULTS: Bone marrow necrosis was diagnosed in fifteen out of 5043 examined specimens with a percentage of 0.3% and ranged from mild to massive according to semiquantitative estimation. Prognosis of all patients was poor with survival not exceeding 6 months from the date of marrow necrosis diagnosis. CONCLUSION: In Egyptian patients, bone marrow necrosis in association with malignancy is a rare disorder which is accompanied by a poor outcome. PMID- 22776812 TI - Stereotactic radiosurgery and radiotherapy in benign intracranial meningioma. AB - PURPOSE: To investigate the role of stereotactic radio surgery (SRS) and hypo fractionated stereotactic radiotherapy (SRT) in treatment of benign intracranial meningioma. PATIENTS AND METHODS: Between 2003 and 2010, 32 patients with a median age of 44 years (range 21-67 years) were treated with SRS (n=19), and hypo fractionated SRT (n=13) for intracranial meningioma. Fourteen patients underwent SRS or SRT as their primary treatment, while 18 patients underwent post operative SRS or SRT (PORT). Cumulative progression free survival, overall cumulative survival, toxicity and symptomatology were evaluated. RESULTS: The median follow up period was 39 months (range 6-72 months). The 5 year overall survival and progression free survival were 90 +/- 5% and 94 +/- 4% after SRT or SRS respectively. Symptoms were improved or stable in 94% of patients. Acute toxicity was mild, and was seen in 41% of patients. Clinically significant late morbidity or new cranial nerve palsies did not occur. CONCLUSION: Stereotactic radio surgery (SRS) and hypo-fractionated stereotactic radiotherapy (SRT) are effective and safe treatment modality for local control of meningioma with low risk of significant late toxicity. In case of large tumor size and adjacent critical structures, hypo-fractionated SRT is highly recommended. PMID- 22776814 TI - Laparoscopic hysterectomy in the treatment of endometrial cancer: NCI experience. AB - BACKGROUND: The standard treatment for women with endometrial cancer is total abdominal hysterectomy and pelvic lymphadenectomy for surgical staging. Total laparoscopic radical hysterectomy (TLH) is an alternative approach providing surgical and patient related advantages to laparoscopy. METHODS: Twenty female patients with early stage endometrial cancer were operated upon by TLH and pelvic lymphadenectomy, aiming to assess the safety and efficacy of TLH. RESULTS: The mean operative time was 296.8 min conversion to laparotomy was done in one patient due to bleeding from the uterine vessels. The mean blood loss was 517.5 cc. The uterus was removed transvaginally in 18 patients (90%) and via a small Pfannenstiel incision in two patients (10%). The mean number of pelvic lymph nodes retrieval was 21.2. Postoperative bleeding occurred in one patient (5%) which necessitated exploration. One patient (5%) suffered a pulmonary embolism. Four patients (20%) developed pyrexia, and one patient (5%) suffered from a chest infection. One patient (5%) had wound infection. The mean hospital stay was 4.5 days (range 3-10). CONCLUSION: TLH with pelvic lymphadenectomy is a safe and effective approach in the treatment of early endometrial carcinoma. PMID- 22776815 TI - Reliability of fine needle aspiration cytology (FNAC) as a diagnostic tool in cases of cervical lymphadenopathy. AB - PURPOSE: The aim of this work is to evaluate the reliability and diagnostic accuracy of fine needle aspiration cytology (FNAC) of cervical lymph nodes with an emphasis on discordant cases between the cytology and the histopathology. PATIENTS AND METHODS: This retrospective study was conducted on 157 selected patients with cervical lymphadenopathy that had undergone FNAC. Cervical nodal enlargement was the first clinical manifestation of the patients in all cases. Hypocelluar slides were excluded from the current study. The cytopathological diagnoses were compared with the histopathological results of the same excised nodes. For all discordant cases, special attention was focused on the cytomorphological features. Diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and discordance rate were calculated. RESULTS: The cytological diagnoses were found to be benign in 48 cases (30.6%) and malignant in 109 cases (69.4%). The overall diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of FNAC of cervical lymph nodes were 90.9%, 67.2%, 82.6%, and 81.3%, respectively. The overall diagnostic accuracy was 82.2% (129/157), while the overall discordance rate was 17.8% (28/157). The diagnostic accuracy of reactive lymphoid hyperplasia, chronic necrotizing lymphadenitis, chronic granulomatous lymphadenitis, metastatic carcinoma, Hodgkin lymphoma, and Non Hodgkin lymphoma was 85%, 83.3%, 70%, 100%, 77.8%, and 75%, respectively. CONCLUSION: The overall diagnostic accuracy of FNAC of cervical lymph nodes was 82.2% while the overall discordance rate was 17.8%. The evaluation of FNA in patients with no previously diagnosed malignancy should be interpreted by an experienced cytopathologist in the context of clinical, radiological, and laboratory finding and if any of these findings is suspicious, further investigation is justified to overcome the limitations and pitfalls of the cytomorphological features when applied alone. PMID- 22776816 TI - Epidemiology and management of breast carcinoma in Egyptian males: experience of a single Cancer Institute. AB - OBJECTIVE: To assess the epidemiological and clinico-pathological features, surgical and reconstructive techniques, adjuvant treatments and clinical outcome of breast carcinoma in males (BCM) at the Egyptian National Cancer Institute (NCI). PATIENTS AND METHODS: Thirty-two males with breast carcinoma presented to NCI between January 2000 and December 2002. They were evaluated by complete history, physical examination, laboratory and radiological investigations. RESULTS: Median age was 59 years. Left sided and retroareolar breast lumps were the commonest presentations. Grade II tumors positive for hormone receptors were very common. Stages I, II, III and IV of the disease were encountered in 6.2%, 34.4%, 34.4% and 25.0% of patients, respectively. Curative surgery was done in 22 patients; they received adjuvant hormonal therapy, chemotherapy and radiotherapy in 22, 16 and 10 patients, respectively. Eight metastatic patients were treated with palliative measures. Surgery was done in 25 patients; the most common procedure was modified radical mastectomy (40.6%). Primary closure was feasible in 17 patients (68%), local flaps were needed in 4 cases (16%), while myocutaneous flap was done in 3 cases (12%). The commonest complication was the development of seroma (9 cases). The overall survival (OS) at 5 years was 65.4%. The disease free survival (DFS) at 5 years was 53.9%. Stage and curative surgery significantly affected OS, while type of surgery was the only variable significantly affecting DFS. CONCLUSION: Male breast carcinoma occurs at older ages than females, usually in advanced stage. This necessitates directing attention of males and awareness on the prevalence and risk factors for this disease. PMID- 22776817 TI - Deletion of cognate CD8 T cells by immature dendritic cells: a novel role for perforin, granzyme A, TREM-1, and TLR7. AB - Immature dendritic cells (imDCs) can have a tolerizing effect under normal conditions or after transplantation. However, because of the significant heterogeneity of this cell population, it is extremely difficult to study the mechanisms that mediate the tolerance induced or to harness the application of imDCs for clinical use. In the present study, we describe the generation of a highly defined population of imDCs from hematopoietic progenitors and the direct visualization of the fate of TCR-transgenic alloreactive CD4(+) and CD8(+) T cells after encountering cognate or noncognate imDCs. Whereas CD4(+) T cells were deleted via an MHC-independent mechanism through the NO system, CD8(+) T-cell deletion was found to occur through a unique MHC-dependent, perforin-based killing mechanism involving activation of TLR7 and signaling through Triggering Receptor-1 Expressed on Myeloid cells (TREM-1). This novel subpopulation of perforin-expressing imDCs was also detected in various lymphoid tissues in normal animals and its frequency was markedly enhanced after GM-CSF administration. PMID- 22776818 TI - Clinical characteristics and outcome of refractory/relapsed myeloid leukemia in children with Down syndrome. AB - Myeloid leukemia in Down syndrome (ML-DS) is associated with good response to chemotherapy and favorable prognosis. Because little research has been focused on refractory/relapsed (R/R) cases, we conducted a retrospective analysis for R/R ML DS. Among ML-DS patients diagnosed between 2000 and 2010 in Japan, 26 relapsed (25 in the BM and 1 in the skin), and 3 refractory patients were enrolled. The male/female ratio was 18/11. The median age at initial diagnosis of ML-DS was 2 years, and the median time to relapse was 8.6 months. Each patient initially had been treated with ML-DS-specific protocols. Thirteen of the 26 patients achieved complete remission with various kinds of reinduction chemotherapies; 2 of 8 survived without further recurrence after receiving allogeneic hematopoietic stem cell transplantation, and 4 of 5 maintained complete remissions with chemotherapy alone. Treatment failures mostly were associated with disease progression rather than treatment-related toxicities. The 3-year OS rate was 25.9% +/- 8.5%. A longer duration from initial diagnosis to relapse was a significant favorable prognostic factor (P < .0001). We conclude that clinical outcome for patients with R/R ML-DS generally are unfavorable, even in those receiving hematopoietic stem cell transplantation. Novel methods to identify poor prognostic factors for ML-DS are necessary. PMID- 22776819 TI - Chronic estradiol treatment reduces platelet responses and protects mice from thromboembolism through the hematopoietic estrogen receptor alpha. AB - Although estrogens are known to have a deleterious effect on the venous thrombosis risk and a preventive action on the development of arterial atheroma, their effect on platelet function in vivo remains unclear. Here, we demonstrate that a chronic high physiologic level of estradiol (E2) in mice leads to a marked decrease in platelet responsiveness ex vivo and in vivo compared with ovariectomized controls. E2 treatment led to increased bleeding time and a resistance to thromboembolism. Hematopoietic chimera mice harboring a selective deletion of estrogen receptors (ERs) alpha or beta were used to demonstrate that the effects of E2 were exclusively because of hematopoietic ERalpha. Within ERalpha the activation function-1 domain was not required for resistance to thromboembolism, as was previously shown for atheroprotection. This domain is mandatory for E2-mediated reproductive function and suggests that this role is controlled independently. Differential proteomics indicated that E2 treatment modulated the expression of platelet proteins including beta1 tubulin and a few other proteins that may impact platelet production and activation. Overall, these data demonstrate a previously unrecognized role for E2 in regulating the platelet proteome and platelet function, and point to new potential antithrombotic and vasculoprotective therapeutic strategies. PMID- 22776820 TI - Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells. AB - We recently defined a critical role for p53 in regulating the quiescence of adult hematopoietic stem cells (HSCs) and identified necdin as a candidate p53 target gene. Necdin is a growth-suppressing protein and the gene encoding it is one of several that are deleted in patients with Prader-Willi syndrome. To define the intrinsic role of necdin in adult hematopoiesis, in the present study, we transplanted necdin-null fetal liver cells into lethally irradiated recipients. We show that necdin-null adult HSCs are less quiescent and more proliferative than normal HSCs, demonstrating the similar role of necdin and p53 in promoting HSC quiescence during steady-state conditions. However, wild-type recipients repopulated with necdin-null hematopoietic stem/progenitor cells show enhanced sensitivity to irradiation and chemotherapy, with increased p53-dependent apoptosis, myelosuppression, and mortality. Necdin controls the HSC response to genotoxic stress via both cell-cycle-dependent and cell-cycle-independent mechanisms, with the latter occurring in a Gas2L3-dependent manner. We conclude that necdin functions as a molecular switch in adult hematopoiesis, acting in a p53-like manner to promote HSC quiescence in the steady state, but suppressing p53-dependent apoptosis in response to genotoxic stress. PMID- 22776822 TI - Using virtual reality environment to improve joint attention associated with pervasive developmental disorder. AB - The focus of this study is using data glove to practice Joint attention skill in virtual reality environment for people with pervasive developmental disorder (PDD). The virtual reality environment provides a safe environment for PDD people. Especially, when they made errors during practice in virtual reality environment, there is no suffering or dangerous consequences to deal with. Joint attention is a critical skill in the disorder characteristics of children with PDD. The absence of joint attention is a deficit frequently affects their social relationship in daily life. Therefore, this study designed the Joint Attention Skills Learning (JASL) systems with data glove tool to help children with PDD to practice joint attention behavior skills. The JASL specifically focus the skills of pointing, showing, sharing things and behavior interaction with other children with PDD. The system is designed in playroom-scene and presented in the first person perspectives for users. The functions contain pointing and showing, moving virtual objects, 3D animation, text, speaking sounds, and feedback. The method was employed single subject multiple-probe design across subjects' designs, and analysis of visual inspection in this study. It took 3 months to finish the experimental section. Surprisingly, the experiment results reveal that the participants have further extension in improving the joint attention skills in their daily life after using the JASL system. The significant potential in this particular treatment of joint attention for each participant will be discussed in details in this paper. PMID- 22776821 TI - Parent report of antidepressant, anxiolytic, and antipsychotic medication use in individuals with Williams syndrome: effectiveness and adverse effects. AB - Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage regarding their child or adult with WS. Twenty-four percent (24%) of the individuals had been prescribed an SSRI medication, while 12% had been prescribed another type of antidepressant or anxiolytic. Overall, 81% of respondents indicated that SSRI medications were either "Helpful" or "Somewhat Helpful", with paroxetine reported to be the least helpful. Sixty-four percent (64%) of survey participants reported that non-SSRI antidepressants and anxiolytics were either "Helpful" or "Somewhat Helpful" in treating symptoms of anxiety. Side effects for the antidepressants and anxiolytics were typically neurological in nature. Ten percent (10%) of the survey participants reported taking an antipsychotic medication, with risperidone and quetiapine described as more helpful than aripiprazole. Medication effectiveness may be related to the impact on serotonin levels. These findings call for further studies of medication usage in WS in order to improve their quality of life. PMID- 22776823 TI - Parallel versus sequential processing in print and braille reading. AB - In the current study we investigated word, pseudoword and story reading in Dutch speaking braille and print readers. To examine developmental patterns, these reading skills were assessed in both children and adults. The results reveal that braille readers read less accurately and fast than print readers. While item length has no impact on word reading accuracy and speed in the group of print readers, it has a significant impact on reading accuracy and speed in the group of braille readers, particularly in the younger sample. This suggests that braille readers rely more strongly on an enduring sequential reading strategy. Comparison of the different reading tasks suggests that the advantage in accuracy and speed of reading in adult as compared to young braille readers is achieved through semantic top-down processing. PMID- 22776824 TI - Dapagliflozin monotherapy in drug-naive patients with diabetes: a randomized controlled trial of low-dose range. AB - AIMS: Many patients with type 2 diabetes are suboptimally managed with currently available therapies. Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, has shown efficacy in reducing diabetic hyperglycaemia. This study assessed efficacy of three lower doses in recently diagnosed patients. METHODS: This phase 3, randomized, double-blind, placebo-controlled study assigned treatment-naive patients to placebo or dapagliflozin monotherapy (1, 2.5 or 5 mg) daily for 24 weeks. Patients were antidiabetic drug-naive with inadequate glycaemic control [haemoglobin A1c (HbA1c) >=7.0 and <=10.0%]. The primary efficacy endpoint was change in HbA1c from baseline. Secondary endpoints included changes in body weight and fasting plasma glucose (FPG), and proportions achieving HbA1c <7%. RESULTS: A total of 282 patients with type 2 diabetes were randomly assigned to one of four treatment groups. Baseline characteristics were similar across groups. At week 24, mean HbA1c reduction was significantly greater with dapagliflozin: -0.68% for 1 mg, -0.72% for 2.5 mg, -0.82% for 5 mg, versus 0.02% for placebo (p < 0.0001); compared to mean baseline values of 7.8-8.1%. Mean FPG reduction was significantly greater for all dapagliflozin groups versus placebo (p < 0.02), as was mean weight reduction (p < 0.003). During the treatment period, 19.1% of placebo-treated patients received rescue medication or discontinued because of poor glycaemic control versus 6.9, 4.1 and 5.9% for dapagliflozin 1, 2.5 and 5 mg, respectively. Percentages of patients experiencing >=1 adverse event were similar across groups. CONCLUSION: Dapagliflozin at doses of 1, 2.5 and 5 mg/day is effective in reducing glycaemic levels and body weight in treatment-naive patients with type 2 diabetes. Dapagliflozin was generally well tolerated. This insulin-independent mechanism suggests a new treatment for type 2 diabetes. PMID- 22776825 TI - The translational imperative: making cell therapy simple and effective. AB - The current practice of cell therapy, in which multipotent or terminally differentiated cells are injected into tissues or intravenously, is inefficient. Few therapeutic cells are retained at the site of administration and engraftment is low. An injectable and biologically appropriate vehicle for delivery, retention, growth and differentiation of therapeutic cells is needed to improve the efficacy of cell therapy. We focus on a hyaluronan-based semi-synthetic extracellular matrix (sECM), HyStem(r), which is a manufacturable, approvable and affordable clinical product. The composition of this sECM can be customized for use with mesenchymal stem cells as well as cells derived from embryonic or induced pluripotent sources. In addition, it can support therapeutic uses of progenitor and mature cell populations obtained from skin, fat, liver, heart, muscle, bone, cartilage, nerves and other tissues. This overview presents four pre-clinical uses of HyStem(r) for cell therapy to repair injured vocal folds, improve post-myocardial infarct heart function, regenerate damaged liver tissue and restore brain function following ischemic stroke. Finally, we address the real-world limitations - manufacture, regulation, market acceptance and financing - surrounding cell therapy and the development of clinical combination products. PMID- 22776826 TI - Month of birth does not seem to interfere with the development of multiple sclerosis later in life in Brazilian patients. PMID- 22776827 TI - Reduced folate, increased vitamin B(12) and homocysteine concentrations in women delivering preterm. AB - BACKGROUND AND AIM: Maternal nutrition is an important determinant of the duration of pregnancy and fetal growth, and thereby influences pregnancy outcome. Folic acid and vitamin B(12) are involved in one-carbon metabolism and are reported to underlie intrauterine programming of adult diseases. METHODS: In the present study, the levels of folate, vitamin B(12) and homocysteine were measured in mothers delivering preterm (PT; gestation <37 weeks; n = 67), those delivering preterm due to preeclampsia (PT-PE; n = 49) and women delivering at term (control group; n = 76). RESULTS: Increased vitamin B(12) and homocysteine levels (p < 0.05 for both) were seen in the PT-PE and PT groups as compared to the controls. In addition, reduced folate levels (p < 0.05) were observed in the PT group. A negative association of maternal plasma homocysteine with birth weight was seen in the idiopathic preterm group. CONCLUSIONS: Altered maternal micronutrients and resultant increased homocysteine concentrations exist in women delivering preterm. These alterations may also be partly associated with other factors such as undiagnosed inflammatory conditions or inadequate placentation in some women. Since these micronutrients play an important role in epigenetic regulation of vital genes involved in the fetal programming of adult diseases, further studies need to be undertaken to understand their role in preterm deliveries. PMID- 22776828 TI - Clinical efficacy and safety of the newer antiepileptic drugs as adjunctive treatment in adults with refractory partial-onset epilepsy: a meta-analysis of randomized placebo-controlled trials. AB - OBJECTIVE: To evaluate the clinical efficacy and safety of the newer antiepileptic drugs (AEDs), namely, Eslicarbazepine (ESL), Retigabine/Ezogabine (RTG), Carisbamate (CAR), Lacosamide (LAC), Brivaracetam (BRI) or Perampanel (PER) as adjunctive therapy for adults with partial-onset seizures (POS). METHODS: A systematic review of Randomized placebo-controlled Trials (RCTs) of newer AEDs was conducted. Electronic databases and identified bibliographies were searched to retrieve RCTs. The primary outcomes were responder rates and withdrawal rates, adverse effects. Pooled effects of odds ratio (OR), risk ratio (RR) and risk differences (RD) were derived from meta-analysis implemented in Revmen 5.1. RESULTS: In total, 15 RCTs were included. All the studies contained a baseline and treatment phase. The pooled OR of all newer AEDs vs placebo was 2.16 (95% CI: 1.82, 2.57) for responder rates, 1.54 (1.12, 2.10) for withdrawal rates, 1.67 (1.34, 2.08) for adverse effects. The indirect comparisons between individual newer AED and all other newer AEDs suggested the similar results in responder rates (ORs, BRI 1.79 [-1.50, 5.08], RTG 1.41 [0.49, 2.33]). CONCLUSIONS: The pooled ORs suggested newer AEDs might be more effective than placebo while with higher incidence of adverse effects. The indirect comparisons suggested BRI, followed by RTG, might be more effective than all other newer AEDs, which could be confirmed by future clinical studies. PMID- 22776829 TI - Effects of iron oxide nanoparticle labeling on human endothelial cells. AB - Iron oxide nanoparticles (INOPS) are a potential contrast agent for magnetic resonance (MR) tracking of transplanted endothelial cells. The objective of this study was to examine the effect of INOPS labeling on endothelial cells. The mixture of INOPS and poly-l-lysine (PLL) was used to label human endothelial cells. Labeling efficiency was examined by Prussian blue staining, transmission electron microscopy, and atomic absorption spectrometry. The effect of iron oxide concentration on cell viability and proliferation were determined. The correlation of reactive oxygen species (ROS) and apoptosis was also examined. In vitro MRI scanning was carried out using a 1.5T MR system. INOPS-PLL could be readily taken up by endothelial cells and subsequently induce MRI signal intensity changes. However, higher labeling concentration (>50 ug/ml) and longer incubation (48 h) can affect cell viability and proliferation. Mitochondrial damage, apoptosis, and autolysosmes were observed under high INOPS-PLL concentrations, which were correlated to ROS production. INOPS-PLL nanoparticles can be used to label transplanted endothelial cells. However, high concentration of INOPS can impair cell viability, possibly through ROS-mediated apoptosis and autophagy. PMID- 22776830 TI - Fetal presentation of long QT syndrome--evaluation of prenatal risk factors: a systematic review. AB - OBJECTIVE: This systematic review evaluated the existence of risk factors for the fetal manifestation of long QT syndrome (LQTS). METHODS: Prenatal cardiac findings suggestive of fetal LQTS were studied using 30 English literature reports extracted from the Pubmed database (1979 to December 2011) using the search terms 'long QT syndrome', 'fetal arrhythmia' and 'congenital heart disease'. RESULTS: LQTS accounted for 15-17% of fetal bradycardias <110 bpm among fetuses with a normally structured heart. Of the patients with significant prenatal findings of LQTS, 17-35% exhibited a reduced baseline fetal heart rate (FHR) of 110-120 bpm on electronic cardiotocography. Other prenatal signs were sinus or intermittent bradycardia <110 bpm arising from atrioventricular block, tachyarrhythmias, pleural effusion and hydrops. More than 30% of Japanese infants with LQTS born at or after the mid-1980s exhibited the above-mentioned in utero signs. CONCLUSIONS: Fetal factors including a slightly reduced baseline FHR of 110-120 bpm, bradycardia <110 bpm, tachyarrhythmias or clinical signs of heart failure, such as pleural effusion and hydrops, were associated with a higher frequency of LQTS. The use of these signs may help to increase the perinatal diagnosis of LQTS. PMID- 22776831 TI - Effect of solution chemistry on multi-walled carbon nanotube deposition and mobilization in clean porous media. AB - There are increasing concerns over the environmental impact and health risks of carbon nanotubes (CNTs) because they may be released into soil and groundwater systems. The present work systematically investigated the transport, deposition, and mobilization behaviors of multi-walled carbon nanotubes (MWNTs) in saturated columns packed with acid-cleaned glass beads and quartz sand of two different grain sizes. Combined effects of pH (5.6 and 10) and ionic strength (IS: DI water, 1mM, and 10mM) on the fate and transport of the MWNTs in the columns were examined. MWNTs were relatively mobile in all the tested conditions with DI water as the experimental solution. Their deposition in the saturated porous media, however, was very sensitive to solution chemistry, particularly IS. Slight increase in solution IS (1 mM) caused strong deposition of MWNTs in both quartz sand (>44%) and glass beads (>39%). Mobilization experimental results indicated that most of the MWNT attachment (>73%) to the porous media was irreversible and reduction in solution IS only caused a small portion of re-entrainment (<27%) of deposited MWNT for all the tested conditions. This indicates that more MWNTs are trapped in the primary minimum, although the deposition of MWNTs in saturated porous media occurs in both primary and secondary minimum. It is suggested that, under unfavorable conditions, weak associated MWNTs in the secondary minimum may be transferred into the primary minimum due to the effect of hydrodynamic force and/or local favorable sites associated with surface heterogeneity. PMID- 22776832 TI - Estimation of contaminant subslab concentration in vapor intrusion. AB - This study is concerned with developing a method to estimate subslab perimeter crack contaminant concentration for structures built atop a vapor source. A simple alternative to the widely-used but restrictive one-dimensional (1-D) screening models is presented and justified by comparing to predictions from a three-dimensional (3-D) CFD model. A series of simulations were prepared for steady-state transport of a non-biodegradable contaminant in homogenous soil for different structure construction features and site characteristics. The results showed that subslab concentration does not strongly depend on the soil diffusivity, indoor air pressure, or foundation footprint size. It is determined by the geometry of the domain, represented by a characteristic length which is the ratio of foundation depth to source depth. An extension of this analytical approximation was developed for multi-layer soil cases. PMID- 22776833 TI - MDG-1, a polysaccharide from Ophiopogon japonicus exerts hypoglycemic effects through the PI3K/Akt pathway in a diabetic KKAy mouse model. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ophiopogon japonicus is a traditional Chinese medicine that might be helpful for the treatment of type 2 diabetes. Recent studies have confirmed its beneficial properties, but not the mechanism of action. AIM OF STUDY: In this study, we examined the effects of a water-soluble beta-d-fructan (MDG-1) from O. japonicus on type 2 diabetes through the PI3K/Akt pathway in a diabetic KKAy mouse model. MATERIALS AND METHODS: MDG-1 was extracted from the tube root of O. japonicus and purified as described previously (Xu et al., 2005). The KKAy mice were gavaged once daily with either distilled water, MDG-1or rosiglitazonefor 8 weeks. Blood glucose levels were tested regularly for the fed and fasted mice. In order to evaluate the effect of MDG-1 on disease progression, the proteins of InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 were detected by Western blotting and serum TG, TC, HDL-C, LDL-C were also dertermined. RESULTS: MDG-1 reduced the hyperglycemia, hyperinsulinemia and hyperlipidemia in the KKAy mice. The oral glucose tolerance test (OGTT) and the level of insulin in the serun showed that insulin resistance in KKAy mice was ameliorated after MDG-1 treated. After 8 weeks treatment with 300mg/kg MDG-1, the content of triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) the serum decreased significantly. Meanwhile high density lipoprotein cholesterol (HDL-C) content increased notably. MDG-1 did not have any effect on total cholesterol (TC) content in the serum, whereas rosiglitazone significantly decreased the TC content. In addition, MDG-1 upregulates the phosphoinositide 3 kinase p85 subunit, Akt, insulin receptor (InsR), insulin receptor substrate-1 (IRS-1) and Glut-4 expression, but downregulates glycogen synthase kinase 3beta expression. CONCLUSIONS: These data indicate that MDG-1 has remarkable anti diabetic activity through the InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 signaling pathway. We believe that MDG-1 is a promising anti-diabetic compound that will be helpful for the treatment of T2DM. PMID- 22776835 TI - Clinical use of placental hormones in pregnancy management. AB - Across human pregnancy, placenta represents a transit of oxygen and nutrients from the mother to the fetus and actively produces a large number of hormones that serve to regulate and balance maternal and fetal physiology. An abnormal secretion of placental hormones may be part of the pathogenesis of the main obstetric syndrome, from early to late pregnancy, in particular chromosomopathies, miscarriage, gestational trophoblastic diseases, preeclampsia, gestational diabetes, and pre-term delivery. The possibility to measure placental hormones represents an important tool not only for the diagnosis and management of gestational disorders, but it is also fundamental in the early identification of women at risk for these pregnancy complications. In the last decades, the use of ultrasound examination has provided additional biophysical markers, improving the early diagnosis of gestational diseases. In conclusion, while few placental hormones have sufficient sensitivity for clinical application, there are promising new biochemical and biophysical markers that, if used in combination, may provide a valid screening tool. PMID- 22776834 TI - Antinociceptive, anti-inflammatory and wound healing features in animal models treated with a semisolid herbal medicine based on Aleurites moluccana L. Willd. Euforbiaceae standardized leaf extract: semisolid herbal. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Aleurites moluccana L. (Willd) Euforbiaceae is a native tree of Indonesia and India that has become acclimatized and well-adapted to the South and Southwest of Brazil. It is commonly used in traditional medicine to treat pain, fever, inflammation, asthma, hepatitis, headache, gastric ulcer, cuts, skin sores and other ailments. The oral antinociceptive effects of standardized 70:30 (v/v) ethanol:water spray dried extract of A. moluccana leaf, as well as its flavonoids 2"-O-rhamnosylswertisin (I) and swertisin (II), have previously been reported. AIM: The aim of this study was to develop a stable and effective semisolid herbal medicine for topical use in the treatment of pain, inflammation and wound healing, containing 0.5 and 1.0% of standardized dried extract of A. moluccana. MATERIALS AND METHODS: The chemical markers I and II were assayed by HPLC-UV analysis after extraction by matrix solid dispersion phase (MSDP) followed analytical validation as ICH Guidelines. The semisolid preparations of Hostacerin CG((r)) vehicle containing 0.5 and 1.0% of dried extract of A. moluccana were submitted to stability studies (180 day of accelerated and long-term studies). The phytomedicine semisolid was analysed in croton oil-induced ear oedema model in mice, in the healing process, using the excisional wound model in rats, and to prevent mechanical sensitization following plantar incision in rats in the postoperative model of pain. RESULTS: The MSDP method showed average recovery of 101.6 and 105.7% for I and II, respectively, with good precision (RSD<2.0%) and selectivity, without interference of the excipients. The formulations were approved in the stability studies, maintaining conformity after 180 day of accelerated and long-term studies, with variation<10% in the analytical parameters. The phytomedicine reduced the ear oedema in 37.6+/ 5.7% and 64.8+/-6.2%, for 0.5 and 1.0% of dried extract, respectively. The formulation also accelerated the healing process by up to 50.8+/-4.1% and 46.0+/ 4.0% at 0.5 and 1.0% of extract, respectively, and both amounts were capable of preventing the development of mechanical sensitization following plantar incision in rats. CONCLUSIONS: The MSDP followed by HPLC-UV analytical method was appropriate for the quality control of the topical phytomedicine based on A. moluccana. The formulation developed at 0.5 and 1.0% of A. moluccana dried extract proved to be effective as an analgesic, anti-inflammatory and wound healing in the pre-clinical studies, which is in agreement with the ethnopharmacological data. PMID- 22776836 TI - Volumetric analysis of cranial vault distraction for cephalocranial disproportion. AB - The purpose of this study was to provide an objective analysis and quantify the intracranial volume change produced by cranial vault distraction osteogenesis. We recently published a technique to expand the cranial vault by distraction in symptomatic patients with findings of cephalocranial disproportion. Resolution of symptoms was documented in that publication. In this current study, we analyzed postdistraction intracranial volume changes in 11 consecutive patients retrospectively from 10/2001 to 11/2010 with institutional review board approval. These 11 patients were treated by cranial vault distraction osteogenesis for symptomatic cephalocranial disproportion. Pre- and postoperative CT DICOM data were analyzed using specialized software to generate finite element models. Intracranial and ventricular volumes were calculated. Topographical surface maps were generated to document and quantify areas of change. Possible effects on brain physiology are discussed. Pre- and postoperative CT scans were obtained at an average of 3.5 months prior to, and 4.2 months following distraction, respectively. Average age at distraction was 55.72 months (range 26-104 months). Operative time averaged 2 h 44 min (range 127-198 min, SD = 30.6). Intracranial and ventricular volumes increased by an average of 77.01 and 4.85 ml, respectively. Nonventricular intracranial volumes increased by 5.91%, 71.67 ml following distraction. All postoperative volume changes were statistically significant (p <= 0.000025). The ability to use the same methodology to quantify ventricular volume changes was unexpected. The fact that all ventricles expanded after distraction at approximately 10% of the total intracranial volume increase indicates that compensatory mechanisms had been activated. We conclude that this occurs at the expense of cerebral blood flow. PMID- 22776837 TI - On the magnetic structure of Sr3Ir2O7: an x-ray resonant scattering study. AB - This report presents azimuthal dependent and polarization dependent x-ray resonant magnetic scattering at the Ir L(3) edge for the bilayered iridate compound Sr(3)Ir(2)O(7). The two magnetic wave vectors, k1 = (1/2, 1/2, 0) and k2 = (1/2, -1/2, 0), result in domains of two symmetry-related G-type antiferromagnetic structures, denoted A and B, respectively. These domains are approximately 0.02 mm(2) and are independent of the thermal history. An understanding of this key aspect of the magnetism is necessary for an overall picture of the magnetic behaviour in this compound. The azimuthal and polarization dependence of the magnetic reflections, relating to both magnetic wavevectors, show that the Ir magnetic moments in the bilayer compound are oriented along the c axis. This contrasts with single layer Sr(2)IrO(4) where the moments are confined to the ab plane. PMID- 22776839 TI - Predictive value of immunohistochemical expression of claudin-1 in colonic carcinoma. AB - OBJECTIVE: Colonic carcinoma is one of the most common cancers worldwide. Recently, the possible involvement of claudin-1, one of the major tight junction proteins, in the process of tumorigenesis has been suggested. Also, claudin-1 has emerged as a potential prognostic factor in different types of tumors. The aim of this study was to detect caludin-1 expression in colonic carcinoma and to correlate its expression with clinicopathological variables in an attempt to delineate its role as a potential new prognostic marker. MATERIAL AND METHODS: Immunohistochemical expression of claudin-1 was assessed in 50 Egyptian patients with colonic adenocarcinoma. The predictive performance of claudin-1 expression was statistically evaluated. RESULTS: Decreased claudin-1 expression was found in 62% of colonic adenocarcinoma cases while similar expression was found in 38% of the cases. Statistical analysis showed a statistically significant inverse correlation between claudin-1 expression and tumor grade, depth of invasion, lymph node involvement, and tumor stage. Regression analysis showed that claudin 1 decreased expression significantly predicts that the tumor is of a high grade, high stage, and is associated with lymph node involvement. ROC curve analysis showed that claudin-1 had a sensitivity of 88.24% and a specificity of 81.25% for the prediction of tumor stage and a sensitivity of 73.33% and a specificity of 82.86% for the prediction of lymph node involvement. CONCLUSIONS: Claudin-1 decreased expression in colonic carcinoma contributes to tumor dedifferentiation, invasion and metastasis. Claudin-1 expression could be used as a predictor of colonic carcinoma stage and lymph node status with a high sensitivity and specificity. PMID- 22776840 TI - Orthotopic neobladder reconstruction after radical cystectomy in patients with a solitary functioning kidney: clinical outcome and evaluation. AB - OBJECTIVE: To evaluate, in a prospective study, the clinical outcome of orthotopic neobladder reconstruction after radical cystectomy in patients with a solitary functioning kidney at the time of surgery. PATIENTS AND METHODS: This study included a total of 28 patients (25 males and three females) with muscle invasive bladder cancer and a solitary functioning kidney at the time of surgery who underwent radical cystectomy (anterior pelvic excentration for females) and urinary reconstruction using orthotopic neobladder at The National Cancer Institute, Cairo University between February 2004 and April 2009. The surgical procedures included ileocaecal neobladder in 19 patients, ileal neobladder (Studer) in five and sigmoid neobladder in four. All perioperative and long-term complications were recorded. The renal functions were evaluated using mainly serum creatinine level, abdominal ultrasonography and intravenous urography (IVU). RESULTS: The mean age of patients was 51.4years (range of 38-62years) while the mean follow-up period was 41.4months (range 18-62months). Early complications included wound infections in five patients, urine leakage in six, abdominal dehiscence with deep venous thrombosis in two, intestinal obstruction and prolonged ileus in three. During the follow-up period, 21 renal units (75%) remained stable with normal serum creatinine level and normal radiological configuration of the kidney. The remaining seven patients (25%) developed varying degrees of renal deterioration either due to uretero-intestinal stricture in three patients (10.7%), who were all treated by open surgical revision of the anastomotic sites or due to stricture at the vesico-urethral anastomosis in four patients (14.3%) that had been successfully managed by endoscopic dilatation and internal urethrotomy with stabilization of renal function. Severe metabolic acidosis occurred in one patient while mild forms occurred in three. These four patients required sodium bicarbonate therapy and their metabolic status was normalized thereafter. CONCLUSION: Selecting the type of urinary diversion is important in patients with a solitary functioning kidney after radical cystectomy. Orthotopic neobladder reconstruction is a good choice in properly selected patients and could provide comparatively satisfactory results. Accordingly, a solitary functioning kidney should not be regarded as a contraindication for neobladder reconstruction after radical cystectomy. PMID- 22776841 TI - Laparoscopy with laparoscopic ultrasound for pretreatment staging of hepatic focal lesions: a prospective study. AB - INTRODUCTION: The need for accurate intrahepatic staging is crucial for patients with primary or secondary hepatic malignancies. Currently available data indicate that laparoscopy with laparoscopic ultrasound provides information similar to that obtained by intraoperative ultrasound and that it is able to identify small intrahepatic lesions not diagnosed by preoperative conventional imaging techniques. OBJECTIVE: To determine the role of preoperative laparoscopy and laparoscopic ultrasonography in patients with potentially resectable hepatic focal lesion or candidate for radiofrequency ablation based on preoperative imaging. MATERIAL AND METHODS: From March 2004 to March 2007, 55 patients with potentially resectable hepatic focal lesions were candidates for exploratory laparotomy based on preoperative abdominal ultrasonography and triphasic spiral CT. All cases were then reevaluated prior to surgery using laparoscopy and laparoscopic ultrasound. All these procedures were performed within a time period of no more than 4 weeks. The data obtained were compared to those obtained by the preoperative conventional imaging studies as regards the presence of satellites, subcentimetric lesions, newly discovered deep parynchymatous lesions, liver condition, portal vein thrombosis, nodal metastases, ascites, peritoneal implants, size and site of the primary lesion. RESULTS: After performing ultrasound-guided laparoscopy, fourteen patients proved to be unfit for surgical resection or ablation, seven patients showed newly discovered focal lesions, five patients proved to have satellites around the tumor and peritoneal deposits, one patient had ascites and one patient had been falsely diagnosed as HCC, proved to have had a liver abscess. CONCLUSION: Preoperative laparoscopy and laparoscopic ultrasonography as an adjunct to preoperative imaging techniques provide more accurate staging for patients with potentially resectable hepatic focal lesions. PMID- 22776842 TI - High expression of LMO2 in Hodgkin, Burkitt and germinal center diffuse large B cell lymphomas. AB - BACKGROUND AND AIM: The LMO2 gene encodes a transcription factor that regulates key events in erythropoiesis, angiogenesis, and embryogenesis and is highly expressed at the most immature stages of lymphopoiesis. Its implication in Hodgkin lymphoma (HL), Burkitt lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) is limited in the literature. MATERIAL AND METHODS: An immunohistochemical study was performed on 68 lymphoma specimens showing different types including Hodgkin lymphoma (23), Burkitt lymphoma (10) and diffuse large B cell lymphoma (35). Also, seven specimens of the reactive nodal tissue were included as control. A monoclonal anti-human antibody has been used to detect LMO2. RESULTS: LMO2 was detected in all cases of HL (100%), in nine cases of BL (90%) and in all cases of DLBCL of germinal center (GC) subtype 20/35 (57.1%) but is completely negative in non-germinal center (NGC) DLBCL. In normal control of reactive nodes, LMO2 was expressed in germinal center area but not expressed in other areas including mantle, marginal, or T cell zones. In DLBCL; there was no statistically significant relation between LMO2 positive cases and the studied clinicopathological parameters including patient's age, sex and tumor site, stage and histological subtype. On the other hand, it was statistically significant regarding immunophenotyping of GC versus NGC. CONCLUSIONS: LMO2 expression is a special feature of GC DLBCL which can be used as a diagnostic marker and therapeutic target. Further studies regarding its prognostic role in patients are recommended. PMID- 22776843 TI - Diagnostic value of p53 and ki67 immunostaining for distinguishing benign from malignant serous effusions. AB - BACKGROUND: The differentiation of benign mesothelial cells from malignant tumor cells, primary, or metastatic, in serous effusions based on cytomorphologic features alone can be problematic. PURPOSE: This study was conducted to evaluate the utility of p53 and ki67 immunocytochemical markers in differentiating benign from malignant tumor cells in serous effusions. PATIENTS AND METHODS: Archival Papanicolaou-stained smears of 91 pleural and peritoneal effusions were retrieved from Cytology Unit, Pathology Department, NCI, Cairo University between 2008 and 2010. Forty-one cases were positive for malignant cells and 50 cases were benign based on cytomorphologic features. Cases having doubt were excluded from the study. The slides were destained and subjected to immunocytochemical staining for p53 and ki67. Histologic sections of colonic carcinoma and tonsillar tissue were used as positive control for p53 and ki67, respectively. Smears having >5% positively stained nuclei for p53 were taken as positive and labeling index ?10% of ki67 was considered positive. Frequencies of the individual immunocytochemical stains; p53 and ki67, in benign and malignant effusion as well as the combination of both stains were calculated. RESULTS: p53 immunostaining showed nuclear positivity in 31 out of 41 malignant effusions (75.6%) and in 3 out of 50 benign effusions (6%), p<0.005. p53 had 75.6% sensitivity, 94% specificity, 91.2% PPV, and 82.5% NPV. ki67 immunostaining was positive in 30 out of 41 malignant effusions (73.2%) and in 17 out of 50 benign effusions (34%), p<0.05. ki67 had 73.2% sensitivity, 66% specificity, 63.8% PPV, and 75% NPV. Cases were then analyzed for combined immunoprofile of p53 and ki67. Among the 24 cases that coexpressed both antigens, 22 cases (91.7%) were malignant. Thirty two out of 34 cases (94.1%) that showed negative results for both antigens were benign. For the cases that showed p53 immunostaining only, 9 out of 10 cases (90%) were malignant. Fifteen out of 23 cases (65.2%) that showed ki67 immunostaining were benign. CONCLUSION: Benign and malignant effusions showed significantly different staining pattern for p53 and ki67. When used individually, p53 immunostaining can truly diagnose 75.6% and 94% of the malignant and benign cases, respectively. ki67 immunostaining can correctly identify 73.2% and 66% of the malignant and benign cases, respectively. When used in combination, 91.7% of p53 and ki67 positive cases were malignant while 94% of p53 and ki67 negative cases were benign. Hence they could be used when the cytomorphology fails to provide a definitive diagnosis. PMID- 22776844 TI - Oncoplastic volume replacement with latissimus dorsi myocutaneous flap in patients with large ptotic breasts. Is it feasible? AB - BACKGROUND: Oncoplastic breast conservative surgery has evolved as a safe alternative to the standard mastectomy in the treatment of early breast cancer. The procedure involves tumour resection with an adequate safety margin and either breast reshaping with volume displacement procedures (large or ptotic breasts) or volume replacement with latissimus dorsi myocutaneous flap (LDF) (small to medium sized non-ptotic breasts). A contra lateral mastopexy procedure is usually necessary with the volume displacement oncoplastic surgery, a procedure that is often rejected by a significant number of patients. This limits the choice of the reconstruction of breast defects in such patients to autologous tissues i.e. LDF. AIM: Aim is to evaluate the feasibility of volume replacement oncoplastic breast conservative surgery with latissimus dorsi myocutaneous flaps for patients with large ptotic breasts. This involves testing the oncologic safety in terms of adequate safety margin, the complications rate and the final cosmetic outcome. The loco regional recurrence rate will be recorded and compared with oncoplastic volume displacement for similar sized breast defects. PATIENTS AND METHODS: A group of 50 female patients with early breast cancers (T2) who presented to the department of surgery at the National Cancer Institute, Cairo, Egypt in the period between January 2004 and November 2009 were included in the study. Bilateral soft tissue mammography was carried out in all patient groups and was used to annually follow up the patients. All patients were detected with T2 N0 breast cancer by both clinical and radiological examinations. All patients underwent partial mastectomy and reconstruction with LDFs. RESULTS: The average age at presentation was 46.5+/-9years and the range was 26-65years. Most of the patients were subjected to partial mastectomy in 30 patients (60%), excision of a single quadrant from the four major quadrants was carried out in 15 patients (30%) where skin sparing wide local excision was carried out in only five patients (10%). The safety margin ranged from 1.1 to 3.2cm with an average of 1.8+/-0.5cm. There was no total flap loss in any patient where as we reported partial flap loss in two patients. Nipple and areola sloughing were reported in two patients, wound infection in five patients, haematoma in four patients, seroma in 16 patients, and donor site morbidity in six patients. The vast majority of patients were either satisfied (score >3 out of 5) (62%) or very satisfied (score 4 or more) (18%) with the results of reconstruction. CONCLUSION: The results of the current study showed the feasibility and the versatility of volume replacement oncoplastic surgery in patients with large ptotic breasts with myocutaneous flaps. The adequacy of safety margin and the acceptable complications rate as well as the comparable local recurrence rate to volume displacement oncoplastic surgery, make it a suitable alternative in a subset of patients who object an immediate contra lateral mastopexy procedure. PMID- 22776845 TI - Differential expression of cyclin D1 in human pituitary tumors: relation to MIB-1 and p27/Kip1 labeling indices. AB - BACKGROUND: Pituitary tumors are a common form of endocrine neoplasia. However few studies assessed the expression of the principal cyclin regulating checkpoint exit, cyclin D1. Cyclin D1 expression in pituitary tumors and its possible relation to MIB-1 and p27/Kip1 labeling indices (LIs) was explored. DESIGN: We studied a total of 199 pituitaries, including normal pituitaries (n=7), pituitary adenomas (n=187), and pituitary carcinoma (n=5). All tissues were tested as cores of archived tissue microarrays that were immunostained for cyclin D1, MIB-1 and p27 using a standard technique. Tissue cores were subjected to automated analysis to evaluate the staining LIs. RESULTS: No cyclin D1 positive cells in the normal anterior pituitary gland was found. Sparse nuclear staining was noted in pituitary tumors. Higher expression of cyclin D1 was noted in pituitary carcinomas compared to adenomas (p<0.001), in non-functioning adenomas compared to functioning ones (p<0.001) in macroadenomas versus microadenomas (p=0.017) and in recurrent non recurrent adenomas (p<0.001). Cyclin D1 LI and MIB-1 LI were related among adenomas (p<0.001) and carcinomas (p=0.041). p27 LI was neither related to pituitary adenoma recurrence nor invasion. CONCLUSIONS: Expression of cyclin D1 in pituitary tumors is related to cell proliferation, recurrence, and metastatic potential. Nuclear cyclin D1 expression is a good marker of aggressive behavior in pituitary tumors. PMID- 22776846 TI - Classification images and bubbles images in the generalized linear model. AB - Classification images and bubbles images are psychophysical tools that use stimulus noise to investigate what features people use to make perceptual decisions. Previous work has shown that classification images can be estimated using the generalized linear model (GLM), and here I show that this is true for bubbles images as well. Expressing the two approaches in terms of a single statistical model clarifies their relationship to one another, makes it possible to measure classification images and bubbles images simultaneously, and allows improvements developed for one method to be used with the other. PMID- 22776847 TI - The role of crowding in contextual influences on contour integration. AB - Dakin and Baruch (2009) investigated how context influences contour integration, specifically reporting that near-perpendicular surrounding-elements reduced the exposure-duration observers required to localize and determine the shape of contours (compared to performance with randomly oriented surrounds) while near parallel surrounds increased this time. Here, we ask if this effect might be a manifestation of visual crowding (the disruptive influence of "visual clutter" on object recognition). We first report that the effect generalizes to simple contour-localization (without explicit shape-discrimination) and influences tolerance to orientation jitter in the same way it affects threshold exposure duration. We next directly examined the role of crowding by quantifying observers' local uncertainty (about the orientation of the elements that comprised our contours), showing that this largely accounts for the effects of context on global contour integration. These findings support the idea that context influences contour integration at a predominantly local stage of processing and that the local effects of crowding eventually influence downstream stages in the cortical processing of visual form. PMID- 22776848 TI - Fixation-related potentials in visual search: a combined EEG and eye tracking study. AB - We report a study of concurrent eye movements and electroencephalographic (EEG) recordings while subjects freely explored a search array looking for hidden targets. We describe a sequence of fixation-event related potentials (fERPs) that unfolds during ~ 400 ms following each fixation. This sequence highly resembles the event-related responses in a replay experiment, in which subjects kept fixation while a sequence of images occurred around the fovea simulating the spatial and temporal patterns during the free viewing experiment. Similar responses were also observed in a second control experiment where the appearance of stimuli was controlled by the experimenters and presented at the center of the screen. We also observed a relatively early component (~150 ms) that distinguished between targets and distractors only in the freeviewing condition. We present a novel approach to match the critical properties of two conditions (targets/distractors), which can be readily adapted to other paradigms to investigate EEG components during free eye-movements. PMID- 22776849 TI - A decade after the Women's Health Initiative--the experts do agree. PMID- 22776850 TI - Effect of the intake of resveratrol, resveratrol phosphate, and catechin-rich grape seed extract on markers of oxidative stress and gene expression in adult obese subjects. AB - BACKGROUND: The preventive effect of resveratrol (RES) on the development of human diseases has been verified by numerous epidemiological studies. Resveratrol triphosphate (RTP) is a stable derivative of RES in which phosphate groups protect the phenolic groups. AIMS: This study compared the effect of RTP on biochemical and molecular markers of oxidative stress to equimolar doses (0.66 mmol) of RES and catechin-rich grape seed extract (CGSE) in a model of oxidative and metabolic stress associated with obesity in humans. METHODS: Thirty-two obese subjects (BMI between 30 and 40) were enrolled. They all received 1 capsule of placebo/day for 28 days before being randomly devised into three arms receiving 1 capsule/day of RES, CGSE, or RTP during the following consecutive 28 days. Blood samples were collected at baseline, after the end of placebo intake, and after the end of the investigational product intake. Biochemical parameters of oxidative stress and blood expression of 200 redox-related genes were determined at each time point. RESULTS: RTP and CGSE showed better antioxidant activities compared to RES and induced important modulations of gene expression. CONCLUSION: The results suggest that RTP and CGSE could contribute to a significant reduction of oxidative stress in obese subjects. PMID- 22776852 TI - Low serum adiponectin levels in Korean children with a family history of type 2 diabetes mellitus. AB - BACKGROUND/AIMS: The current worldwide increases of type 2 diabetes mellitus (T2DM) in children coincide with increases in the prevalence of obesity. We investigated the insulin resistance and adiponectin levels of children and adolescents with a family history of T2DM (FHD). METHODS: Our sample included 131 children and adolescents aged 8-15 years. Fasting plasma glucose, lipids, fasting insulin, adiponectin levels and HOMA-IR were analyzed according to FHD and obesity. Oral glucose tolerance tests were performed in all subjects except non obese subjects without FHD. RESULTS: Adiponectin levels of subjects with FHD were significantly lower than those of subjects without FHD in both the obese and nonobese groups. HOMA-IR was significantly higher in obese subjects with FHD than in those without FHD. Adiponectin levels were found to be independently associated with FHD and Matsuda index. The frequency of impaired glucose tolerance in obese subjects with FHD was more than four times higher compared to obese subjects without FHD. CONCLUSION: Our results suggest that FHD could be a risk factor of T2DM in obese Korean children, especially with low serum levels of adiponectin. PMID- 22776851 TI - The rising challenge of non-AIDS-defining cancers in HIV-infected patients. AB - Since the advent of HAART, patients with HIV infection have seen a significant improvement in their morbidity, mortality, and life expectancy. The incidence of AIDS-defining illnesses, including AIDS-defining malignancies, has been on the decline. However, deaths due to non-AIDS-defining illnesses have been on the rise. These so-called non-AIDS-defining cancers (NADCs) include cancers of the lung, liver, kidney, anus, head and neck, and skin, as well as Hodgkin's lymphoma. It is poorly understood why this higher rate of NADCs is occurring. The key challenge facing oncologists is how to administer chemotherapy effectively and safely to patients on antiretroviral therapy. The challenge to clinicians caring for HIV-infected patients is to develop and implement effective means to screen, treat, and prevent NADCs in the future. This review presents data on the epidemiology and etiology of NADCs, as well as ongoing research into this evolving aspect of the HIV epidemic. PMID- 22776854 TI - SU-75: a disordered Ge10 germanate with pcu topology. AB - A disordered open-framework germanate, denoted as SU-75, was synthesized under hydrothermal conditions using diethylenetriamine (dien) or alternatively 1,4 diaminobutane (dab) as the structure directing agent (SDA). SU-75 crystallizes in a tetragonal space group I42d (No. 122) with a = 18.145(3) A and c = 41.701(9) A. The three-dimensional (3D) framework is built from Ge(10)(O,OH)(28) (Ge(10)) clusters that are connected following the pcu (primitive cubic) net topology. SU 75 has 10-, 11- and 12-ring channels along the a- and b-axes and channels with alternating 8-, 10-, 12-, 10-ring openings along the c-axis. The framework exhibits a serious disorder, resulted from two possible connectivities between the units of four Ge(10) clusters (4Ge(10) unit). The chemical formula of SU-75 is |(H(2)SDA)(2)(H(2)O)(n)|[Ge(10)O(21)(OH)(2)] (SDA = dien or dab, n = 5-6), determined by combining single crystal synchrotron X-ray diffraction, thermogravimetric analysis (TGA) and CHN elemental analysis. A superoctahedron is introduced to simplify the description of the connectivity of the Ge(10) clusters and to illustrate the disorder. This is also used to compare the structure of SU 75 with those of related Ge(10) germanates. PMID- 22776853 TI - Cryptic del/dup aberration of 60.6 Mb at 5q15-5q23.3 predicting adult-onset leukodystrophy. AB - We report on a de novo interstitial del/dup aberration consisting of a 13.3 Mb deletion of 5q15-5q21.3 (92.1-105.4 Mb, hg19) and a 23.6 Mb tandem direct duplication of 5q21.3-5q23.3 (106.1-129.7 Mb, hg19). Although the aberration covered a total of 60.6 Mb, it was cryptic, i.e., not detectable by karyotyping at a resolution of 430 bands. Array-CGH indicated a diploid region of 0.6 Mb between the duplicated and the deleted segment. The aberration affected a 14 month-old boy conceived after intracytoplasmic sperm injection who presented with developmental delay, muscular hypotonia, partial agenesis of the corpus callosum, prominent forehead, low set ears, hypertelorism, hyperopia, wide-bridged nose, retrognathia, high palate, and cryptorchidism. The duplicated segment comprised the LMNB1 gene, thus predicting adult-onset autosomal-dominant leukodystrophy and revealing a temporal dimension of the phenotype. Counseling problems implicated by this prediction include "the right not to know" that the patient might want to exercise when coming of age. PMID- 22776856 TI - Fingerprints of spin-orbital entanglement in transition metal oxides. AB - The concept of spin-orbital entanglement on superexchange bonds in transition metal oxides is introduced and explained on several examples. It is shown that spin-orbital entanglement in superexchange models destabilizes the long-range (spin and orbital) order and may lead either to a disordered spin-liquid state or to novel phases at low temperature which arise from strongly frustrated interactions. Such novel ground states cannot be described within the conventionally used mean field theory which separates spin and orbital degrees of freedom. Even in cases where the ground states are disentangled, spin-orbital entanglement occurs in excited states and may become crucial for a correct description of physical properties at finite temperature. As an important example of this behaviour we present spin-orbital entanglement in the RV O(3) perovskites, with R = La,Pr,...,Y b,Lu, where the finite temperature properties of these compounds can be understood only using entangled states: (i) the thermal evolution of the optical spectral weights, (ii) the dependence of the transition temperatures for the onset of orbital and magnetic order on the ionic radius in the phase diagram of the RV O(3) perovskites, and (iii) the dimerization observed in the magnon spectra for the C-type antiferromagnetic phase of Y V O(3). Finally, it is shown that joint spin-orbital excitations in an ordered phase with coexisting antiferromagnetic and alternating orbital order introduce topological constraints for the hole propagation and will thus radically modify the transport properties in doped Mott insulators where hole motion implies simultaneous spin and orbital excitations. PMID- 22776855 TI - Assessment of sleep apnea syndrome in treated acromegalic patients and correlation of its severity with clinical and laboratory parameters. AB - BACKGROUND: Sleep apnea syndrome (SAS) is a frequent disorder in acromegalic patients and its frequency ranges from 45 to 87.5% of patients. Obstructive SAS is the prevailing form in acromegaly and its pathogenesis is based on craniofacial deformations and thickening of soft tissues and mucosas of upper airways and bronchi. Central and mixed types are less frequent. Respiratory complications, and SAS in particular, may contribute to the increased mortality observed in acromegaly. AIM: Aim of the present study is to assess the presence of SAS in acromegalic patients, its features and to correlate the severity of SAS with factors such as disease duration, body mass index (BMI), smoking, GH/IGF-I serum levels, associated comorbidities. SUBJECTS AND METHODS: Polygraphy (SOMNOcheck Effort Weinmann V2.05) was performed in 25 consecutive acromegalic patients (9 men and 16 women). Statistical analysis was performed with Mann Whitney's test and Spearman coefficient. RESULTS: Fourteen out of 25 patients (56%) were affected by SAS. The prevailing form was obstructive SAS (12/14 patients). Smoking, female gender, and presence of lung disease appear to lead to a more severe form. We also found that the prevalence of hypertension was significantly higher in the group of patients with SAS, whereas no correlation was proved among SAS and disease duration, GH/IGF-I serum levels, somatostatin analogs treatment, BMI, and associated comorbidities. CONCLUSIONS: SAS is a frequent complication of acromegaly. Severe forms seem to be correlated with smoking and lung disease. Therefore, all acromegalic patients should be subjected to a polygraphic study for an early diagnosis and treatment and smoking should be discouraged. PMID- 22776858 TI - Porous graphitic carbon nitride synthesized via direct polymerization of urea for efficient sunlight-driven photocatalytic hydrogen production. AB - Energy captured directly from sunlight provides an attractive approach towards fulfilling the need for green energy resources on the terawatt scale with minimal environmental impact. Collecting and storing solar energy into fuel through photocatalyzed water splitting to generate hydrogen in a cost-effective way is desirable. To achieve this goal, low cost and environmentally benign urea was used to synthesize the metal-free photocatalyst graphitic carbon nitride (g C3N4). A porous structure is achieved via one-step polymerization of the single precursor. The porous structure with increased BET surface area and pore volume shows a much higher hydrogen production rate under simulated sunlight irradiation than thiourea-derived and dicyanamide-derived g-C3N4. The presence of an oxygen atom is presumed to play a key role in adjusting the textural properties. Further improvement of the photocatalytic function can be expected with after-treatment due to its rich chemistry in functionalization. PMID- 22776859 TI - Erythrocyte n-3 polyunsaturated fatty acid and seafood intake decrease the risk of depression: case-control study in Korea. AB - BACKGROUND/AIMS: Low intake or tissue levels of n-3 polyunsaturated fatty acids (PUFA) have been associated with an increased risk of depression, but some studies do not support the association. The purpose of the present study was to evaluate the hypothesis that erythrocyte levels of n-3 PUFA and intake of seafood are negatively associated with the risk of depression in Koreans. METHODS: We investigated 80 patients diagnosed with a score >=25 on the Center for Epidemiological Studies Depression Scale, Korean version, and confirmed by a psychiatrist. Eighty-eight controls without a chronic disease were matched to the cases for age and sex. RESULTS: Multivariate-adjusted regression analysis showed that the risk of depression was significantly and negatively associated with erythrocyte levels of 20:5 n-3, 22:6 n-3, 16:0 and 18:0, but positively associated with erythrocyte levels of 18:2t and 16:1 after adjusting for confounding factors. In addition, the risk of depression was negatively associated with the intake of energy, carbohydrate, seafood and grains, but positively with the intake of fat and meat after adjustment for confounding factors. CONCLUSIONS: The risk of depression could be decreased with increased erythrocyte levels of n-3 PUFA and saturated fatty acids, as well as seafood intake, but decreased erythrocyte levels of trans fatty acids in Koreans. PMID- 22776860 TI - Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial. AB - In a phase 2 study, continued denosumab treatment for up to 8 years was associated with continued gains in bone mineral density and persistent reductions in bone turnover markers. Denosumab treatment was well tolerated throughout the 8 year study. INTRODUCTION: The purpose of this study is to present the effects of 8 years of continued denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTM) from a phase 2 study. METHODS: In the 4-year parent study, postmenopausal women with low BMD were randomized to receive placebo, alendronate, or denosumab. After 2 years, subjects were reallocated to continue, discontinue, or discontinue and reinitiate denosumab; discontinue alendronate; or maintain placebo for two more years. The parent study was then extended for 4 years where all subjects received denosumab. RESULTS: Of the 262 subjects who completed the parent study, 200 enrolled in the extension, and of these, 138 completed the extension. For the subjects who received 8 years of continued denosumab treatment, BMD at the lumbar spine (N = 88) and total hip (N = 87) increased by 16.5 and 6.8 %, respectively, compared with their parent study baseline, and by 5.7 and 1.8 %, respectively, compared with their extension study baseline. For the 12 subjects in the original placebo group, 4 years of denosumab resulted in BMD gains comparable with those observed during the 4 years of denosumab in the parent study. Reductions in BTM were sustained over the course of continued denosumab treatment. Reductions also were observed when the placebo group transitioned to denosumab. Adverse event profile was consistent with previous reports and an aging cohort. CONCLUSION: Continued denosumab treatment for 8 years was associated with progressive gains in BMD, persistent reductions in BTM, and was well tolerated. PMID- 22776862 TI - Association of P2X7 receptor polymorphisms with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients. AB - The P2X7 receptor is thought to be involved in bone physiology in a pro osteogenic manner. Therefore, we examined associations between genetic variations in the P2X7 receptor gene and bone mineral density (BMD). We found an association between four non-synonymous polymorphism of the human P2X7 receptor and the risk of osteoporosis. INTRODUCTION: The purpose of this study was to determine whether genetic variation in the P2X7 receptor gene (P2RX7) is associated with decreased BMD and risk of osteoporosis in fracture patients. METHODS: Six hundred ninety women and 231 men aged>=50 years were genotyped for 15 non-synonymous P2RX7 SNPs. BMD was measured at the total hip, lumbar spine and femoral neck. RESULTS: Four non-synonymous SNPs were associated with BMD. The Ala348Thr gain-of-function polymorphism was associated with increased BMD values at the lumbar spine (p=0.012). Decreased hip BMD values were associated with two loss-of-function SNPs in the P2RX7, i.e., in subjects homozygous for the Glu496Ala polymorphism as well as in subjects carrying at least one variant allele of the Gly150Arg polymorphism (p=0.018 and p=0.011; respectively). In men, we showed that subjects either heterozygous or homozygous for the Gln460Arg gain-of-function polymorphism in the P2RX7 had a significantly 40% decrease in risk of a lower T-score value (OR=0.58 [95%CI, 0.33-1.00]). CONCLUSION: Thus, genetic aberrations of P2X7R function are associated with lower BMD and increased osteoporosis risk. Therefore, detection of non-synonymous SNPs within the P2RX7 might be useful for osteoporosis risk estimation at an early stage, potentially enabling better osteoporosis prevention and treatment. PMID- 22776861 TI - Sarcopenia and its relationship with bone mineral density in middle-aged and elderly European men. AB - The aim of this study was to determine the relationship between reduced muscle mass (sarcopenia) and areal bone mineral density (BMD(a)) in middle-aged and elderly community-dwelling European men. Men with sarcopenia had significantly lower BMD(a) and were more likely to have osteoporosis compared with men without sarcopenia. INTRODUCTION: In men, the relationship between reduced muscle mass (sarcopenia) and BMD(a) is unclear. This study aimed to determine this relationship in middle-aged and elderly community-dwelling men. METHODS: Men aged 40-79 years from the Manchester (UK) and Leuven (Belgium) cohorts of the European Male Ageing Study were invited to attend for assessment including dual-energy X ray absorptiometry, from which appendicular lean mass (aLM), fat mass (FM) and whole-body, spine and hip BMD(a) were determined. Relative appendicular skeletal muscle mass (RASM) was calculated as aLM/height2. Muscle strength was assessed in subjects from Leuven. Sarcopenia was defined by RASM at <7.26 kg/m2 and by the recent definition of the European Working Group on Sarcopenia in Older People (RASM at <7.26 kg/m(2) plus low muscle function). Linear regression was used to determine the associations between aLM, FM, muscle strength and BMD(a) and logistic regression to determine the association between sarcopenia and osteoporosis. RESULTS: Six hundred seventy-nine men with a mean age of 59.6 (SD = 10.7), contributed data to the analysis; 11.9 % were sarcopenic by the conventional definition. After adjustment for age and centre, aLM, RASM and FM were positively associated with BMD(a). Men with RASM at <7.26 kg/m2 had significantly lower BMD(a) compared with those with RASM at >=7.26 kg/m(2). In a multivariable model, aLM was most consistently associated with BMD(a). Men with sarcopenia were more likely to have osteoporosis compared with those with normal RASM (odds ratio = 3.0; 95 % CI = 1.6-5.8). CONCLUSIONS: Sarcopenia is associated with low BMD(a) and osteoporosis in middle-aged and elderly men. Further studies are necessary to assess whether maintaining muscle mass contributes to prevent osteoporosis. PMID- 22776863 TI - Hip fracture and other predictors of anti-osteoporosis drug use in Norway. AB - This study aims to find predictors of anti-osteoporosis drug (AOD) use. Known risk factors of osteoporosis, i.e., age, hip fracture, and corticosteroid use were found to be predictors of AOD use, in addition to a number of other drugs used. Higher socioeconomic position did not favor the use of AOD. INTRODUCTION: This study deals with studying predictors of anti-osteoporosis drug treatment in Norwegian women and men. METHODS: All Norwegian women and men>=50 years were included (n=1,407,392). Data were taken from different data sources, (1) the Norwegian Prescription Database (drug use in 2004-2005); (2) the Nationwide Census 2001 (marital status, education and resident county); (3) the National Hip Fracture Database (hip fractures 2003-2005); and (4) the National Population Register (date of death/emigration). We estimated the hazard ratios (HR) for incident treatment by Cox proportional hazard regression. RESULTS: In 2005, 10,332 women (1.5%) and 1,387 men (0.2%) were new users of anti-osteoporosis drugs (incident treatment). Age was a statistically significant predictor of incident treatment in both women and men, with HR ranging from 1.7 to 3.2 (per 10 years). A middle educational level in men strongly predicted incident treatment [HR 2.0 (CI 1.1-3.8)], but not in women after full adjustment. A previous hip fracture, increasing number of drugs used and use of corticosteroids were all predictors of incident treatment in both genders after adjustments. Corticosteroid use [HRwomen=4.0 (CI 3.8-4.2)] had a higher HR for incident treatment than hip fracture [HRwomen=2.0 (CI 1.8-2.3)]. Marital status and area of residency were not predictors of incident treatment in either gender, after adjustments. The predictors of prevalent treatment were only slightly different from incident treatment in 2005. CONCLUSIONS: Age, previous hip fracture, number of drugs used, and use of corticosteroids were positively related to treatment in both genders. In men, a middle educational level predicted treatment. PMID- 22776864 TI - Cost and management of males with closed fractures. AB - The purpose of this study was to examine the medical costs and the management of osteoporosis in the 12 months after a closed fracture for men aged >= 45 years. The mean medical cost per fracture was high ($6,078-$30,900), and osteoporosis management post fracture was inadequate in the majority of men. INTRODUCTION: This study was conducted in order to examine the medical costs following fracture in males and the management of osteoporosis post fracture. METHODS: Administrative claims from a large, national health plan were analyzed. Men >= 45 years were included if they had >= 1 medical claim for a new closed fracture between January 1, 2005 and December 31, 2008. Commercially insured (COM) and Medicare Advantage Plan (MAP) members were analyzed separately. Costs were calculated as paid amounts and adjusted to 2010 dollars. Both the differences between the individual patients' 12-month pre-fracture and 12-month post-fracture costs and the costs directly attributed to the fracture were reported. The prevalence of dual-energy X-ray absorptiometry (DXA) scan and/or osteoporosis pharmacotherapy treatment was evaluated in the 12 months post fracture. RESULTS: We identified 18,917 (COM, 16,191; MAP, 2,726) men with new closed fractures. Non hip, non-vertebral fractures (NHNV) were the most common fracture in both COM and MAP populations. Fracture costs ranged from $7,121 to $15,830 for vertebral fractures, from $22,601 to $30,900 for hip fractures, and from $6,078 to $8,344 for NHNV fractures. In the COM and MAP populations, respectively, 8.5 and 15.5 % had a DXA scan and/or osteoporosis pharmacotherapy in the 12 months following the fracture. CONCLUSIONS: Healthcare costs associated with fractures in men are substantial. About 1 in 12 men >= 45 years in the COM population were provided adequate follow-up for osteoporosis post fracture. While this rate improved to about one in six men in the MAP population, osteoporosis management in men post fracture is far from optimal. PMID- 22776865 TI - Association of bone turnover markers with mortality in men referred to coronary angiography. AB - We aimed to examine the association of fatal events with osteocalcin (OC) and beta-crosslaps (beta-CTX) levels in men. We observed a U-shaped association of OC and beta-CTX levels with fatal events in a large cohort of men at high cardiovascular risk. INTRODUCTION: Accumulating evidence suggests an association of low OC levels with metabolic disturbances. Whether OC levels are related to fatal events is, however, less clear. Further, high beta-CTX levels are linked to increased mortality. We aimed to examine the association of fatal events with both OC and beta-CTX in men. METHODS: We measured OC and beta-CTX in 2,271 men referred to coronary angiography (1997-2000). RESULTS: We observed a U-shaped association of OC and beta-CTX with fatal events. Crude hazard ratios (HRs) for all-cause and non-cardiovascular mortality in the highest OC quintile were 1.38 (1.04-1.83) and 1.47 (0.89-2.40), respectively, and 2.11 (1.61-2.75) and 2.06 (1.29-3.29) for men in the lowest compared to the third OC quintile. In multivariate-adjusted models, HRs for all-cause, and non-cardiovascular mortality in the lowest OC quintile were 1.63 (1.23-2.16) and 1.79 (1.10-2.92), respectively, compared to the third OC quintile, whereas the association of high OC with mortality lost its significance. Crude and multivariate-adjusted HRs for cardiovascular mortality in the lowest OC quintile compared to the third OC quintile were 2.08 (1.49-2.90) and 1.74 (1.24-2.46), respectively. Moreover, high as well as low beta-CTX levels were independently associated with all-cause (quintile 1 vs. quintile 3: HR 1.42 (1.05-1.92); quintile 5 vs. quintile 3: HR 1.79 (1.31-2.45)) and cardiovascular mortality (quintile 1 vs. quintile 3: HR 1.55 (1.05-2.28); quintile 5 vs. quintile 3: HR 1.85 (1.23-2.77)). CONCLUSIONS: We observed a U-shaped association of OC and beta-CTX with fatal events in a large cohort of men at high cardiovascular risk. PMID- 22776867 TI - Giant encephalocele: a study of 14 patients. AB - BACKGROUND: Giant encephalocele is a rare condition and few published reports are available in the English literature. It is a challenge to neurosurgeons, even today. This series consists of 14 patients with giant encephaloceles treated at our institute. MATERIAL AND OBSERVATION: Over a period of 8 years, from 2002 to 2009, 110 patients with encephaloceles were managed at our institute. Amongst them, 14 were children with giant encephaloceles. All patients had CT/MRI or both prior to surgery, and all were operated upon. Four patients were neonates, under 1 month of age, and 9/14 patients (64%) were under 3 months. The youngest child was a newborn baby aged 2 days. Except for 1 with an anterior encephalocele, the rest were patients with occipital encephaloceles. A CT scan was performed on 5 and an MRI on 1 patient. Both CT and MRI scans were performed on the other 8 patients. MRI/CT showed hydrocephalus in 10/14 patients. Of these, 7 required ventriculoperitoneal (VP) shunt, and the remaining 3 with mild to moderate hydrocephalus did not. Of the 7 patients who underwent VP shunt, 5 had a shunt during the encephalocele repair and 2 had a postoperative shunt for increasing hydrocephalus. RESULTS: Other associated anomalies recorded were acquired Chiari malformation in 3 patients, secondary craniostenosis with microcephaly in 5, and syringomyelia in 1 patient. All the patients underwent repair of encephalocele and 4 had suturectomy of coronal suture for the secondary craniostenosis. There were 2 postoperative deaths due to hypothermia. Among the 12 surviving patients, 9 had a good outcome and 3 had poor mental development. The present study shows overall good outcomes in 9/14 (66%) patients. PMID- 22776868 TI - Estimating energy expenditure from raw accelerometry in three types of locomotion. AB - PURPOSE: Accuracy of estimating activity-related energy expenditure (AEE) from raw body acceleration may improve by using prediction equations that are specific for the type of activity. The current study aims to improve published equations by deriving an equation for overground walking and to evaluate whether overground cycling and stair walking require specific prediction equations. METHODS: Participants (91 male/95 female, 8-81 yr old) were equipped with a triaxial accelerometer (DynaPort MiniMod; McRoberts BV, The Hague, The Netherlands) on their lower back. Total energy expenditure (TEE) was measured using a mobile oxygen analyzer (MetaMax 3b; Cortex Biophysik, Leipzig, Germany). Resting energy expenditure (REE) was measured for 30 min, following which a physical activity course was completed involving walking on level ground at slow (8 min), normal (8 min), and fast speed (3 min), stair walking (3 min), and cycling (8 min). AEE was calculated as TEE - REE, expressed in both absolute (kJ.min) and relative (J.min.kg) units. Mixed linear regression analysis was used for developing regression equations for walking, stair walking, and cycling. RESULTS: Acceleration contributed 76% and 93% (P < 0.001) to explained variance in walking AEE for absolute and relative AEE models, respectively. Age and gender improved estimation accuracy by <1%. Applying a conservative walking equation, AEE (J.min.kg) = -40.19 + 816.11 acceleration (g) (root-mean-square error = 34.00 J.min.kg), to cycling and stair walking resulted in mean bias (95% limits of agreement) of -253 (-449, 46) and -276 (-442, 109) J.min.kg, respectively (approximately 50% bias). Acceleration added 35% and 42% to explained variance in relative AEE (J.min.kg) during cycling and stair walking, respectively; this fraction was approximately 20% for absolute AEE (kJ.min) in both activities. CONCLUSION: AEE during walking can be predicted across a wide age range using raw acceleration, but activity-specific equations are needed for cycling and stair walking. PMID- 22776869 TI - Cardiorespiratory fitness, LDL cholesterol, and CHD mortality in men. AB - INTRODUCTION: There are no published data regarding the joint association of cardiorespiratory fitness (CRF) and LDL cholesterol concentration with subsequent CHD mortality in men. METHODS: A total of 40,718 healthy men received a comprehensive baseline clinical examination between 1971 and 2006. CRF was determined from a maximal treadmill exercise test. Participants were divided into categories of low (quintile 1), moderate (quintiles 2-3), and high (quintiles 4 5) CRF by age group, as well as by Adult Treatment Panel III-defined LDL categories. HRs for CHD mortality were computed with Cox regression analysis. RESULTS: A total of 557 deaths due to CHD occurred during 16.7 +/- 9.0 yr (681,731 man-years) of follow-up. After adjustment for age, examination year, smoking status, family history, and body mass index, a significant positive trend in CHD mortality was shown across decreasing categories of CRF. HRs with 95% confidence interval were 1.0 (referent), 1.18 (0.94-1.47), and 2.10 (1.65-2.67) for high, moderate, and low fit groups, P trend <0.0001. Adjusted HRs were significantly higher across increasing LDL categories: 1.0 (referent), 1.30 (0.87 1.95), 1.54 (1.04-2.28), 2.16 (1.45-3.21), and 2.02 (1.31-3.13), P trend <0.0001. When grouped by CRF category as well as by LDL category, there was a significant positive trend (P < 0.02) in adjusted mortality across decreasing categories of CRF within each LDL category. CONCLUSIONS: CRF is strongly and inversely associated with CHD mortality in men. Compared with men with low CRF, at a moderate to high level of CRF, the risk of mortality within each LDL category is significantly attenuated. This study suggests that measurement of CRF should be considered for routine cardiovascular risk assessment and risk management. PMID- 22776870 TI - Exercise performance over the menstrual cycle in temperate and hot, humid conditions. AB - PURPOSE: This study investigated the effects of the menstrual cycle on prolonged exercise performance both in temperate (20 degrees C, 45% relative humidity) and hot, humid (32 degrees C, 60% relative humidity) conditions. METHODS: For each environmental condition, 12 recreationally active females were tested during the early follicular (day 3-6) and midluteal (day 19-25) phases, verified by measurement of estradiol and progesterone. For all four tests, thermoregulatory, cardiorespiratory, and perceptual responses were measured during 60 min of exercise at 60% of maximal oxygen consumption followed by an incremental test to exhaustion. RESULTS: No differences in exercise performance between menstrual cycle phases were found during temperate conditions (n = 8) despite a higher resting and submaximal exercise core temperature (Tc) in the luteal phase. In hot, humid conditions (n = 8), however, prolonged exercise performance, as exercise time to fatigue, was significantly reduced during the luteal phase. This finding was not only accompanied by higher resting and submaximal exercise Tc but also a higher rate of increase in Tc during the luteal phase. Furthermore, submaximal exercise HR, minute ventilation, and RPE measures were higher during the luteal phase in hot, humid conditions. No significant differences were found over the menstrual cycle in heat loss responses (partitional calorimetry, sweat rate, upper arm sweat composition) and Tc at exhaustion. CONCLUSION: In temperate conditions, no changes in prolonged exercise performance were found over the menstrual cycle, whereas in hot, humid conditions, performance was decreased during the luteal phase. The combination of both exercise and heat stress with the elevated luteal phase Tc at the onset of exercise resulted in physiological and perceptual changes and a greater thermosensitivity, which may explain the decrease in performance. PMID- 22776871 TI - Aggravation of exercise-induced intestinal injury by Ibuprofen in athletes. AB - INTRODUCTION: Nonsteroidal anti-inflammatory drugs are commonly used by athletes to prevent anticipated exercise-induced pain, thereby putatively improving physical performance. However, these drugs may have potentially hazardous effects on the gastrointestinal (GI) mucosa during strenuous physical exercise. The aim of the current study was to determine the effect of oral ibuprofen administration before exercise on GI integrity and barrier function in healthy individuals. METHODS: Nine healthy, trained men were studied on four different occasions: 1) 400 mg ibuprofen twice before cycling, 2) cycling without ibuprofen, 3) 400 mg ibuprofen twice at rest, and 4) rest without ibuprofen intake. To assess small intestinal injury, plasma intestinal fatty acid binding protein (I-FABP) levels were determined, whereas urinary excretion of orally ingested multisugar test probes was measured using liquid chromatography and mass spectrometry to assess GI permeability. RESULTS: Both ibuprofen consumption and cycling resulted in increased I-FABP levels, reflecting small intestinal injury. Levels were higher after cycling with ibuprofen than after cycling without ibuprofen, rest with ibuprofen, or rest without ibuprofen (peak I-FABP, 875 +/- 137, 474 +/- 74, 507 +/- 103, and 352 +/- 44 pg.mL, respectively, P < 0.002). In line, small intestinal permeability increased, especially after cycling with ibuprofen (0-2 h urinary lactulose/rhamnose ratio, 0.08 (0.04-0.56) compared with 0.04 (0.00 0.20), 0.05 (0.01-0.07), and 0.01 (0.01-0.03), respectively), reflecting loss of gut barrier integrity. Interestingly, the extent of intestinal injury and barrier dysfunction correlated significantly (RS = 0.56, P < 0.001). CONCLUSION: This is the first study to reveal that ibuprofen aggravates exercise-induced small intestinal injury and induces gut barrier dysfunction in healthy individuals. We conclude that nonsteroidal anti-inflammatory drugs consumption by athletes is not harmless and should be discouraged. PMID- 22776872 TI - Effects of noradrenaline and dopamine on supraspinal fatigue in well-trained men. AB - PURPOSE: Prolonged exhaustive exercise induces a failure of the nervous system to activate the involved muscles maximally (i.e., central fatigue). Part of central fatigue may reflect insufficient output from the motor cortex (i.e., supraspinal fatigue), but the cause is unresolved. To investigate the potential link between supraspinal fatigue and changes in brain concentration of dopamine and noradrenaline in temperate environment, we combined neurophysiological methods and pharmacological manipulation of these two neurotransmitters. METHODS: Changes in performance of a cycling exercise (time trial [TT]) were tested after oral administration of placebo (Pla), dopamine, or noradrenaline reuptake inhibitors (methylphenidate and reboxetine [Rebox], respectively) in well-trained male subjects. Changes in voluntary activation, corticospinal excitability, and muscle contractile properties were tested in the knee extensors using transcranial magnetic stimulation and motor nerve electrical stimulation before and after exercise. A psychomotor vigilance task (PVT) was also performed. RESULTS: Compared with Pla, methylphenidate did not affect exercise performance (P = 0.19), but more time was needed to complete the TT after administration of Rebox (approximately 9%, P < 0.05). For the latter condition, the reduced performance was accompanied by a central/supraspinal fatigue (5%-6%, P < 0.05) and worsened PVT performance (7%, P < 0.05). For the three conditions, corticospinal excitability was unchanged, and peripheral fatigue was similar. Because the ingestion of Rebox induced a greater decrease in voluntary activation and PVT performance after the TT than Pla, with no modification in corticospinal excitability, the noradrenaline reuptake inhibitor likely affected supraspinal circuits located before the motor cortex. CONCLUSION: These results suggest that noradrenaline, but not dopamine reuptake inhibition, contributes to the development of central/supraspinal fatigue after a prolonged cycling exercise performed in temperate conditions. PMID- 22776873 TI - Assessing volume of accelerometry data for reliability in preschool children. AB - PURPOSE: This study examines what volume of accelerometry data (h.d) is required to reliably estimate preschool children's physical activity and whether it is necessary to include weekday and weekend data. METHODS: Accelerometry data from 493 to 799 (depending on wear time) preschool children from the Melbourne-based Healthy Active Preschool Years study were used. The percentage of wear time each child spent in total (light-vigorous) physical activity was the main outcome. Hourly increments of daily data were analyzed. t-tests, controlling for age and clustering by center of recruitment, assessed the differences between weekday and weekend physical activity. Intraclass correlation coefficients estimated reliability for an individual day. Spearman-Brown prophecy formula estimated the number of days required to reach reliability estimates of 0.7, 0.8, and 0.9. RESULTS: The children spent a significantly greater percentage of time being physically active on weekend compared with weekdays regardless of the minimum number of hours included (t = 12.49-16.76, P < 0.001 for all). The number of days required to reach each of the predetermined reliability estimates increased as the number of hours of data per day decreased. For instance, 2.7-2.8 d of data were required to reach a reliability estimate of 0.7 with 10 or more hours of data per day; 3.3-3.4 d were required to meet the same reliability estimate for days with 7 h of data. CONCLUSIONS: Future studies should ensure they include the minimum amount of data (hours per day and number of days) as identified in this study to meet at least a 0.7 reliability level and should report the level of reliability for their study. In addition to weekdays, at least one weekend day should be included in analyses to reliably estimate physical activity levels for preschool children. PMID- 22776874 TI - Effects of fractionized and continuous exercise on 24-h ambulatory blood pressure. AB - PURPOSE: The objective of this study is to compare the effects of fractionized aerobic exercise (three 10-min exercise sessions) and continuous exercise (one 30 min exercise session) on 24-h ambulatory blood pressure (ABP). METHODS: Eleven healthy prehypertensive subjects (28.3 +/- 8.0 (SD) yr) completed three randomly assigned conditions: 1) three 10-min sessions of aerobic exercise (3 * 10 min), 2) one continuous 30-min session of aerobic exercise (1 * 30 min), and 3) a nonexercise control trial (control). The mode of exercise was walking on a motor driven treadmill at 75%-79% of maximum heart rate (HRmax) (60%-65% VO2peak). Twenty-four-hour ABP was monitored with an automated ABP device (Oscar 2TM; SunTech Medical, Morrisville, NC). Linear mixed models were used to compare 24-h ABP responses between trials. RESULTS: The mean +/- SD 24-h systolic blood pressure (SBP) was significantly lower during the 3 * 10-min trial (127 +/- 15 mm Hg) compared with control (130 +/- 15 mm Hg) (P < 0.001). Although both 3 * 10 min and 1 * 30-min trials reduced SBP compared with control during daytime/evening (1300-2300 h), only the 3 * 10-min trial reduced SBP during nighttime (2300-0800 h, 118 +/- 16 vs 122 +/- 14 mm Hg, P = 0.024) and the following morning (0800-1200 h, 127 +/- 15 vs 131 +/- 15 mm Hg, P = 0.016). For 24 h, 26.7% of SBP values during 3 * 10 min were normal (i.e., <120 mm Hg) compared with 18.3% for 1 * 30 min and 19.4% for control (P < 0.001). CONCLUSIONS: In prehypertensive individuals, fractionized exercise (e.g., three 10-min aerobic exercise sessions spread and effective exercise alternative to continuous exercise for cardiovascular risk reduction in this population. PMID- 22776875 TI - Reduced satellite cell numbers with spinal cord injury and aging in humans. AB - INTRODUCTION: Both sarcopenia and spinal cord injury (SCI) are characterized by the loss of skeletal muscle mass and function. Despite obvious similarities in atrophy between both models, differences in muscle fiber size and satellite cell content may exist on a muscle fiber type-specific level. METHODS: In the present study, we compared skeletal muscle fiber characteristics between wheelchair dependent young males with SCI (n = 8, 32 +/- 4 yr), healthy elderly males (n = 8, 75 +/- 2 yr), and young controls (n = 8, 31 +/- 3 yr). Muscle biopsies were collected to determine skeletal muscle fiber type composition, fiber size, and satellite cell content. RESULTS: Severe atrophy and a shift toward approximately 90% Type II muscle fibers were observed in muscle obtained from males with SCI. Muscle fiber size was substantially smaller in both the SCI (Types I and II fibers) and elderly subjects (Type II fibers) when compared with the controls. Satellite cell content was substantially lower in the wheelchair-dependent SCI subjects in both the Types I and II muscle fibers (0.049 +/- 0.019 and 0.050 +/- 0.005 satellite cells per fiber, respectively) when compared with the young controls (0.104 +/- 0.011 and 0.117 +/- 0.009 satellite cells per fiber, respectively). In the elderly, the number of satellite cells was lower in the Type II muscle fibers only (0.042 +/- 0.005 vs 0.117 +/- 0.009 satellite cells per fiber in the elderly vs young controls, respectively). CONCLUSION: This is the first study to show that muscle fiber atrophy as observed with SCI (Types I and II fibers) and aging (Type II fibers) is accompanied by a muscle fiber type specific reduction in satellite cell content in humans. PMID- 22776876 TI - Relationship between physical activity and brain atrophy progression. AB - INTRODUCTION: Brain atrophy is associated with impairment in cognitive function and learning function. The aim of this study was to determine whether daily physical activity prevents age-related brain atrophy progression. METHODS: The participants were 381 men and 393 women who had participated in both the baseline and the follow-up surveys (mean duration = 8.2 yr). Magnetic resonance imaging of the frontal and temporal lobes was performed at the time of the baseline and follow-up surveys. The daily physical activities and total energy expenditures of the participants were recorded at baseline with uniaxial accelerometry sensors. Multiple logistic regression models were fit to determine the association between activity energy expenditure, number of steps, and total energy expenditure variables and frontal and temporal lobe atrophy progression while controlling for possible confounders. RESULTS: In male participants, the odds ratio of frontal lobe atrophy progression for the fifth quintile compared with the first quintile in activity energy expenditure was 3.408 (95% confidence interval = 1.205-9.643) and for the number of steps was 3.651 (95% confidence interval = 1.304-10.219). Men and women with low total energy expenditure were at risk for frontal lobe atrophy progression. There were no significant differences between temporal lobe atrophy progression and physical activity or total energy expenditure. CONCLUSION: The results indicate that physical activity and total energy expenditure are significant predictors of frontal lobe atrophy progression during an 8-yr period. Promoting participation in activities may be beneficial for attenuating age-related frontal lobe atrophy and for preventing dementia. PMID- 22776877 TI - Carotid inflammation is unaltered by exercise in hypercholesterolemic Swine. AB - INTRODUCTION: Reduction of vascular inflammation might contribute to the beneficial effects of exercise. We hypothesized that 1) exercise would reduce carotid endothelial vascular cell adhesion molecule-1 (VCAM-1) and that 2) in vivo detection of carotid inflammation can be achieved in a large animal model using contrast-enhanced ultrasound (CEU) with VCAM-1-targeted microbubbles (MBs). METHODS: Familial hypercholesterolemic (FH) swine were divided into sedentary (Sed) and exercise-trained (Ex) groups. Ex pigs underwent 16-20 wk of treadmill aerobic exercise. At the end of the study, in vivo CEU with VCAM-1-targeted MBs and assessment of endothelial-dependent dilation (EDD) were performed in carotid arteries. VCAM-1 mRNA and protein expression were compared with markers of atherosclerotic disease and health, and in vitro EDD was assessed in carotid arteries. RESULTS: Exercise training neither reduced inflammation nor improved EDD in carotid arteries of FH swine. Markers of atherosclerosis including VCAM-1 were prominent in the bifurcation compared with the proximal or distal common carotid artery and inversely associated with phosphorylated and total endothelial nitric oxide synthase. Signal intensity from VCAM-1-to-control MBs positively correlated with carotid VCAM-1 protein expression, validating our technique. CONCLUSION: These results first demonstrate that aerobic exercise has no effect on carotid endothelial inflammatory markers and EDD in FH swine. Second, our findings indicate that CEU using VCAM-1-targeted MBs can detect inflammation in vivo, providing strong foundations for longitudinal studies examining the effect of therapeutic interventions on the inflammatory status of the endothelium. PMID- 22776879 TI - Basal, circadian, and acute inflammation in normal versus overweight men. AB - Increased inflammation is present in obese compared with normal weight individuals, but inflammation characteristics of nonobese, overweight individuals are less clear. PURPOSE: The objective of this study was to determine whether basal, circadian, and posteccentric exercise inflammation levels differ between normal and overweight men. METHODS: Men (18-35 yr old) classified as normal weight (body mass index <=25 kg.m, n = 20) and overweight (body mass index = 25 30 kg.m, n = 10) completed exercise (EX) and control (CON) conditions in random order. Maximal voluntary effort and eccentric actions (3 * 15) using the elbow flexor muscles of one arm were performed, and blood was collected preexercise and 4, 8, 12, and 24 h postexercise at 7:00 a.m., 12:00 p.m., 4:00 p.m., 8:00 p.m., and 7:00 a.m. Blood was collected on a time-matched schedule without exercise for CON. Soluble tumor necrosis factor receptor-1, interleukin-6, C-reactive protein (CRP), and cortisol responses (EX value - time-matched CON value) were measured. RESULTS: Basal CRP was higher in the overweight compared with normal weight group (mean +/- SD, 0.542 +/- 0.578 vs 1.395 +/- 1.041 mg.L). Soluble tumor necrosis factor receptor-1 increased (P < 0.05) 8 h postexercise in both groups, and the response was greater 12 and 24 h postexercise in the overweight compared with normal weight groups. Interleukin-6 increased (P < 0.05) 8 h postexercise, with a trend (P = 0.09) to be greater in the overweight group. CRP and cortisol responses were not detected. CONCLUSIONS: The low-grade inflammation state in overweight compared with normal weight men includes both higher basal CRP concentrations and enhanced acute inflammation, but not in changes to the circadian patterns of cortisol and inflammation variables. PMID- 22776878 TI - Genetic variation of SCNN1A influences lung diffusing capacity in cystic fibrosis. AB - INTRODUCTION: Epithelial Na channels (ENaCs) play a crucial role in ion and fluid regulation in the lung. In cystic fibrosis (CF), Na hyperabsorption results from ENaC overactivity, leading to airway dehydration. Previous work has demonstrated functional genetic variation of SCNN1A (the gene encoding the ENaC alpha subunit), manifesting as an alanine (A) to threonine (T) substitution at amino acid 663, with the alphaT663 variant resulting in a more active channel. METHODS: We assessed the influence of genetic variation of SCNN1A on the diffusing capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO), together with alveolar-capillary membrane conductance (DM), pulmonary capillary blood volume, and alveolar volume (VA) at rest and during peak exercise in 18 patients with CF (10 homozygous for alphaA663 (AA group) and 8 with at least one T663 allele (AT/TT group)). Because of the more active channel, we hypothesized that the AT/TT group would show a greater increase in DLCO, DLNO, and DM with exercise because of exercise-mediated ENaC inhibition and subsequent attenuation of Na hyperabsorption. RESULTS: The AT/TT group had significantly lower pulmonary function, weight, and body mass index than the AA group. Both groups had similar peak workloads, relative peak oxygen consumptions, and cardiopulmonary responses to exercise. The AT/TT group demonstrated a greater increase in DLNO, DLNO/VA, and DM in response to exercise (% increases: DLNO = 18 +/- 11 vs 41 +/- 38; DLNO/VA = 14 +/- 21 vs 40 +/- 37; DM = 15 +/- 11 vs 41 +/- 38, AA vs AT/TT, respectively). There were no differences between groups in absolute diffusing capacity measures at peak exercise. CONCLUSION: These results suggest that genetic variation of the alpha-subunit of ENaC differentially affects the diffusing capacity response to exercise in patients with CF. PMID- 22776880 TI - Effect of BMI on prediction of accelerometry-based energy expenditure in youth. AB - PURPOSE: The objective of this study is to determine the effect of body mass index (BMI) on level of agreement between six previously established prediction equations for three commonly used accelerometers to predict summary measures of energy expenditure (EE) in youth. METHODS: One hundred and thirty-one youth between the ages of 10-17 yr and BMI from 15 to 44 kg.m were outfitted with hip worn ActiGraph GT1M (Pensacola, FL), Actical (MiniMiter/Respironics, Bend, OR), and RT3 (StayHealthy, Monrovia, CA) accelerometers and spent approximately 24 h in a whole-room indirect calorimeter while performing structured and self selected activities. Five commonly used regression and one propriety equations for each device were used to predict the minute-to-minute EE (normalized to METs), daily physical activity level (PAL), and time spent in sedentary, light, moderate, and vigorous physical activity intensity categories. The calculated values were compared with criterion measurements obtained from the room calorimeter. RESULTS: All predictive equations, except RT3, significantly over- or underpredicted daily PAL (P < 0.001), with large discrepancies observed in the estimate of sedentary and light activity. Discrepancies between actual and estimated PAL ranged from 0.05 to 0.68. In addition, BMI represented a modifier for two ActiGraph predictive equations (AG1 and AG2), affecting the accuracy of physical activity-related EE predictions. CONCLUSION: ActiGraph (AG3) and the RT3 closely predicted overall PAL (within 4.2% and 6.8%, respectively) as a group. When adjusting for age, sex, and ethnicity, Actical (AC1 and AC2) and ActiGraph (AG3) were not influenced by BMI. However, a gap between some hip-worn accelerometer predictive and regression equations was demonstrated compared with both criterion measurement and each other, which poses a potential difficulty for interstudy (e.g., different accelerometers) and intrastudy (e.g., BMI and adiposity) comparisons. PMID- 22776882 TI - A competition-based design to assess performance of a squad of elite athletes. AB - There is need for valid and powerful research designs to assess performance effects of interventions in squads of elite athletes. PURPOSE: The objective of this study is to develop a design for investigating effects on competition performance using performance of athletes in other squads as a control. METHODS: We used competition swim times downloaded from USAswimming.org for a season ending in the US Open and assumed an intervention had been applied to athletes in one of the larger squads (Ford) at one competition (Santa Clara). Data were included only for swimmers who achieved >900 Hy-Tek points at the USA Swimming Nationals. Each swimmer's points were used to select their best event. Times for the resulting 368 best-event swims in seven competitions by 148 swimmers in 19 squads were analyzed to determine the uncertainty (90% confidence interval) of the effect of the hypothetical intervention. Further analyses were performed with other selection criteria. Uncertainties were compared with those in other recent studies of competitive senior swimmers. RESULTS: Uncertainty in the effect of an intervention applied to Ford for Santa Clara would have been +/-0.8%. Applying other data-selection criteria resulted in generally more uncertainty. Uncertainties in recent studies of competitive swimmers using conventional designs ranged between +/-0.7% and +/-2.2%. CONCLUSION: For the sport of swimming, the effects with this new design are at least as precise as those of conventional research designs using performance tests, and the outcomes are likely to have higher validity. The new design should be useful for assessing the effect of an intervention representing a substantial change from a baseline of usual practice in any sport where athletes compete often against athletes of other squads. PMID- 22776881 TI - Expiratory loading improves cardiac output during exercise in heart failure. AB - PURPOSE: The objective of this study was to investigate the effect of changes in expiratory intrathoracic pressure on stroke volume (SV) at rest and during moderate exercise in patients with heart failure versus healthy individuals. METHODS: SV was obtained by echocardiography during spontaneous breathing and during expiratory loads of 5 and 10 cm H2O produced by a ventilator in 11 patients with heart failure (61 +/- yr, ejection fraction: 32 +/- 4%, New York Heart Association, 32% +/- 4%; NYHA class I-II) and 11 age-matched healthy individuals at rest and during exercise at 60% of aerobic capacity on a semirecumbent cycle ergometer. RESULTS: At rest, expiratory loading did not change HR, SV index (SVI), or cardiac index (CI) in either group. During moderate exercise, expiratory loading increased SVI and CI in patients with heart failure but decreased SVI and CI in healthy individuals. There was a negative correlation between changes in gastric pressure and SVI (r = -0.51, P < 0.05) in healthy individuals, whereas there was a positive correlation between changes in gastric pressure accompanying expiratory loading and CI (r = 0.83, P < 0.01) in patients with heart failure. CONCLUSION: Expiratory loading during moderate exercise elicited increases in SVI and CI in patients with heart failure but decreased SVI and CI in healthy individuals. Improvements in cardiac function during submaximal exercise in patients with heart failure may be caused by a beneficial reduction in left ventricular preload. PMID- 22776883 TI - Gas exchange threshold in male speed-power versus endurance athletes ages 20-90 years. AB - PURPOSE: This cross-sectional study compared the oxygen uptake at the gas exchange threshold (GET) and its relation to age between highly trained competitive speed-power athletes (SP), endurance athletes, and untrained participants. METHODS: A total of 199 men ages 20-90 yr were examined: 51 SP, 87 endurance runners (ER), and 61 untrained individuals (UT). Physiological parameters at GET were obtained during a graded treadmill test until exhaustion: oxygen uptake (VO2GET), HRGET, and oxygen pulse (O2 PulseGET). Information about training history and volume was collected. A linear model of regression was adopted. RESULTS: Average VO2GET was lower in the SP than that in ER group but significantly higher in the SP than that in UT group across the whole age range. Absolute rate of decline in VO2GET was smaller in the SP than ER group and smallest in the UT group (0.38, 0.56, and 0.22 mL.kg.min.yr, respectively). Percentage decline per decade did not differ between groups (7.9%-8.7%). Above the age of 50 yr, absolute and percentage rates of decline were considerably lower in the SP than ER group (0.24 vs 0.65 mL.kg.min.yr and 7.2% vs 13.4% per decade, respectively). About the age of 85, the predicted level of VO2GET in the SP group was close to that of the ER group. The training volume correlated significantly with VO2GET in athletes (r = 0.67-0.70). Main predictors of O2GET were VO2 PulseGET and HRGET (89.9%-95.6% and 4.1%-9.8% of explained variance, respectively). CONCLUSIONS: Our results suggest that the "speed-power model" of lifelong physical activity is associated with an elevated level of VO2GET and its relatively slow age-related decline. PMID- 22776884 TI - Bone density, structure and strength, and their determinants in aging sprint athletes. AB - PURPOSE: This study was undertaken to examine bone properties in masters sprinters of different ages and younger reference subjects. In addition, the association of sport-specific ground reaction force, muscle, training, and hormone characteristics with the bone parameters was evaluated in the athletes. METHODS: Bone densitometric, structural, and strength parameters were assessed by peripheral quantitative computed tomography at the distal and midtibia in 83 male sprinters (40-85 yr) and 19 physically active referents (31-45 yr). Between-group differences were analyzed by ANCOVA with body mass and height as covariates. RESULTS: Bone values were generally greater in athletes than referents, the greatest differences being in bending strength of the tibia shaft as estimated by maximum moment of inertia (Imax). Among athletes, trabecular volumetric bone mineral density of distal tibia was 12% (P < 0.05) lower in the oldest (>=70 yr) versus youngest group, whereas the total bone mineral content, total cross sectional area, and compressive bone strength index did not differ between the groups. At midtibia, no age group differences were present in the total bone mineral content, total cross-sectional area, cortical wall thickness, cortical volumetric bone mineral density, polar mass distribution, minimum moment of inertia, or maximum moment of inertia. After controlling for age, body mass, and height, most loading-related characteristics, knee extensor muscle thickness, and hormone concentrations correlated with the bone parameters. Multivariate regression models explained 12%-67% (mean, 47.5%) of the variance of the bone parameters. Mechanical power in the eccentric phase of the hopping and body mass were consistently the strongest independent predictors in the models. CONCLUSION: The results suggest that regular sprint training has positive (direction specific) effects on bone strength and structure in middle- and older-aged athletes. Interindividual differences in bone traits seem to be due to combined effects of exercise loading, body size, and hormonal characteristics. PMID- 22776885 TI - Depression and social support between China' rural and urban empty-nest elderly. AB - This study compared levels of depression and social support among empty-nest elderly who living in the rural and urban area of Hunan province, China. This cross-sectional study enrolled 809 empty-nest elderly living throughout the province as the study respondents. The general information, depression conditions and social supports were investigated by using the self-made General Information Questionnaire, Geriatric Depression Scale (GDS) and Social Support Rating Scale (SSRS). Variables are presented as mean +/- standard deviation (SD) or frequency. Independent t-test and chi(2)-tests were used to compare the socio-demographic factors, depression score and social support scores of the rural empty-nest elderly to the urban empty-nest ones; multilevel modeling was used to analyze the socio-demographic factors and social support predicted the level of depression among the empty-nest old subjects. The differences in gender, education level, marital status, economic status, self-perceived income, insurance, children visit frequency and religious beliefs factors between rural and urban empty-nester old people were statistically significant (p<0.05). The average GDS score of rural group was (14.57 +/- 5.43), which was higher than the average GDS score (13.18 +/ 6.51) of urban group (p<0.01). Objective support scores showed statistical significance between the rural and urban empty-nest elderly (p<0.05). There are differences between rural and urban empty-nest elderly in the aspects of general data, depression status, social support and so on, we should intervene them effectively according to their different characteristics. PMID- 22776886 TI - Imaging mass spectrometry to visualize biomolecule distributions in mouse brain tissue following hemispheric cortical spreading depression. AB - MALDI mass spectrometry can simultaneously measure hundreds of biomolecules directly from tissue. Using essentially the same technique but different sample preparation strategies, metabolites, lipids, peptides and proteins can be analyzed. Spatially correlated analysis, imaging MS, enables the distributions of these biomolecular ions to be simultaneously measured in tissues. A key advantage of imaging MS is that it can annotate tissues based on their MS profiles and thereby distinguish biomolecularly distinct regions even if they were unexpected or are not distinct using established histological and histochemical methods e.g. neuropeptide and metabolite changes following transient electrophysiological events such as cortical spreading depression (CSD), which are spreading events of massive neuronal and glial depolarisations that occur in one hemisphere of the brain and do not pass to the other hemisphere , enabling the contralateral hemisphere to act as an internal control. A proof-of-principle imaging MS study, including 2D and 3D datasets, revealed substantial metabolite and neuropeptide changes immediately following CSD events which were absent in the protein imaging datasets. The large high dimensionality 3D datasets make even rudimentary contralateral comparisons difficult to visualize. Instead non-negative matrix factorization (NNMF), a multivariate factorization tool that is adept at highlighting latent features, such as MS signatures associated with CSD events, was applied to the 3D datasets. NNMF confirmed that the protein dataset did not contain substantial contralateral differences, while these were present in the neuropeptide dataset. PMID- 22776887 TI - Interaction of SLC1A1 gene variants and life stress on pharmacological resistance in obsessive-compulsive disorder. AB - Genetic and environmental factors seem to interact and influence both the onset and the course of obsessive-compulsive disorder (OCD), but the role of glutamate transporter variants (SLC1A1) in pharmacological resistance is not known. We aimed to assess whether genetic variants in SLC1A1 and life stress at onset of the disorder interact and modulate pharmacological resistance in OCD. A single marker association study of several single-nucleotide polymorphisms in the SLC1A1 genomic region was performed in a sample of 238 OCD patients. For the most strongly associated SNP (rs3087879), one copy of the risk allele increased the probability of higher treatment resistance (odds ratio=2.42; 95% confidence interval=1.39-4.21; P=0.0018), but only in OCD patients without life stress at onset of the disorder. These results suggest a gene-by-environment interaction effect on treatment resistance in OCD and strengthen the existing evidence of the role of the glutamatergic system in the phenomenology of OCD. PMID- 22776889 TI - Sequential decision tree using the analytic hierarchy process for decision support in rectal cancer. AB - OBJECTIVE: The aim of the study is to determine the most appropriate method for construction of a sequential decision tree in the management of rectal cancer, using various patient-specific criteria and treatments such as surgery, chemotherapy, and radiotherapy. METHODS: An analytic hierarchy process (AHP) was used to determine the priorities of variables. Relevant criteria used in two decision steps and their relative priorities were established by a panel of five general surgeons. Data were collected via a web-based application and analyzed using the "Expert Choice" software specifically developed for the AHP. Consistency ratios in the AHP method were calculated for each set of judgments, and the priorities of sub-criteria were determined. A sequential decision tree was constructed for the best treatment decision process, using priorities determined by the AHP method. RESULTS: Consistency ratios in the AHP method were calculated for each decision step, and the judgments were considered consistent. The tumor-related criterion "presence of perforation" (0.331) and the patient surgeon-related criterion "surgeon's experience" (0.630) had the highest priority in the first decision step. In the second decision step, the tumor-related criterion "the stage of the disease" (0.230) and the patient-surgeon-related criterion "surgeon's experience" (0.281) were the paramount criteria. The results showed some variation in the ranking of criteria between the decision steps. In the second decision step, for instance, the tumor-related criterion "presence of perforation" was just the fifth. CONCLUSION: The consistency of decision support systems largely depends on the quality of the underlying decision tree. When several choices and variables have to be considered in a decision, it is very important to determine priorities. The AHP method seems to be effective for this purpose. The decision algorithm developed by this method is more realistic and will improve the quality of the decision tree. PMID- 22776888 TI - In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice. AB - BACKGROUND: Interventions to increase brown adipose tissue (BAT) volume and activation are being extensively investigated as therapies to decrease the body weight in obese subjects. Noninvasive methods to monitor these therapies in animal models and humans are rare. We investigated whether contrast ultrasound (CU) performed in mice could detect BAT and measure its activation by monitoring BAT blood flow. After validation, CU was used to study the role of uncoupling protein 1 and nitric oxide synthases in the acute regulation of BAT blood flow. METHODS AND RESULTS: Blood flow of interscapular BAT was assessed in mice (n=64) with CU by measuring the signal intensity of continuously infused contrast microbubbles. Blood flow of BAT estimated by CU was 0.5+/-0.1 (mean+/-SEM) dB/s at baseline and increased 15-fold during BAT stimulation by norepinephrine (1 ug.kg(-1).min(-1)). Assessment of BAT blood flow using CU was correlated to that performed with fluorescent microspheres (R(2)=0.86, P<0.001). To evaluate whether intact BAT activation is required to increase BAT blood flow, CU was performed in uncoupling protein 1-deficient mice with impaired BAT activation. Norepinephrine infusion induced a smaller increase in BAT blood flow in uncoupling protein 1 deficient mice than in wild-type mice. Finally, we investigated whether nitric oxide synthases played a role in acute norepinephrine-induced changes of BAT blood flow. Genetic and pharmacologic inhibition of nitric oxide synthase 3 attenuated the norepinephrine-induced increase in BAT blood flow. CONCLUSIONS: These results indicate that CU can detect BAT in mice and estimate BAT blood flow in mice with functional differences in BAT. PMID- 22776893 TI - Volume 52 of the Journal. Editorial. PMID- 22776890 TI - Thoughts on Sec14-like nanoreactors and phosphoinositide signaling. PMID- 22776894 TI - The Symposium. Foreword. PMID- 22776895 TI - Anthropometric, penile and testis measures in post-pubertal Italian males. AB - BACKGROUND: Relationships between anthropometric measures, body proportions, weight and penile dimensions in young adult males have not been previously analyzed. Furthermore, although male fertility has declined in last decades, no data on testicular volume (the best surrogate measure for spermatogenic potential) are available for the general population of young men in Italy. AIM: To analyze anthropometric measures and proportions, testicular volumes, and penile dimensions in a large cohort from the general population of young Italian men aged 18-19 yr. MATERIALS/SUBJECTS: We analyzed 2019 students aged 18-19 years for height, weight, body mass index (BMI), waist circumference, arm span, pubis to-floor and crown-to-pubis length, and penile dimensions. Testicular volumes were measured by ultrasound in 776 subjects. RESULTS: Thirty-six percent of the subjects had a pathological arm span-height difference (>3 cm) and 44.7% had a pathological pubis-to-floor/ crown-to-pubis ratio (<= 0.92). The mean penis length was 8.9 +/- 1.4 cm and the penis circumference was 9.5 +/- 1.0 cm. BMI was positively associated with arm span-height difference and negatively with penis length; 23.2% of the subjects had low mean testicular volume (<12 ml). CONCLUSIONS: The findings highlight a strong influence of BMI on skeletal proportions and penis length, identify a large proportion of subjects with testicular hypotrophy at risk for future fertility, and suggest to consider worldwide studies to redefine normal values for arm span-height difference and upper/ lower body segment ratio. PMID- 22776896 TI - Tuning the size of gold nanoparticles in the citrate reduction by chloride ions. AB - A new approach was developed to control the size of gold nanoparticles in citrate reduction by altering the concentration of chloride ions. The size of the as prepared gold nanoparticles could be tuned in the range 19-47 nm at a specific molar ratio of citrate and tetrachloroauric acid (5:1) by simply changing the concentration of chloride ions from 0 to 20 mM. UV-visible spectra and TEM observations showed that the increased size of the gold particles was primarily related to the promoted aggregation of the primary gold particles. The aggregation was attributed to their decreased surface charge as the chloride ion concentration in the reaction solutions increased. This approach could also be extended to other reaction systems, for example, the size of gold nanoparticles prepared by NaBH(4) reduction increased from 3 to 12 nm as the chloride ion concentration was increased from 0 to 20 mM. PMID- 22776897 TI - Elevated acetoacetate and monocyte chemotactic protein-1 levels in cord blood of infants of diabetic mothers. AB - BACKGROUND: Infants of diabetic mothers (IDMs) are at increased risk for metabolic complications. Type 1 and some type 2 diabetic patients have elevated levels of the ketone bodies acetoacetate (AA) and beta-hydroxybutyrate (BHB). OBJECTIVE: The aim of this study was to examine how hyperketonemia in diabetic mothers affects markers of inflammation and oxidative stress in their offspring. METHODS: Blood was obtained from 23 diabetic mothers and 13 healthy mothers and their infants' umbilical cords at delivery. Interleukin-8, monocyte chemotactic protein-1 (MCP-1) and protein carbonyl (protein oxidation) levels were determined by ELISA. U937 human monocyte cell culture was used to examine the effect of AA and BHB on secretion of MCP-1. RESULTS: There was a significant increase in the levels of AA in cord blood of IDMs compared with cord blood of infants of healthy mothers. A significant increase in the levels of protein oxidation (p < 0.05) and MCP-1 levels (p < 0.05) was observed in the cord blood of IDMs. The level of MCP 1 correlated significantly (r = 0.51, p = 0.01) with the concentration of AA in the IDMs. In further experiments with cultured monocytes treated with exogenous AA (0-4 mM), a significant increase in MCP-1 secretion was observed in AA- but not BHB-treated monocytes. CONCLUSION: Blood levels of AA and MCP-1 are elevated in IDMs, which may contribute to the development of the metabolic complications seen in IDMs. PMID- 22776898 TI - Unusual oxidation state distributions observed for two mixed-valence heptanuclear manganese disc-like clusters. AB - The synthesis, structures and magnetic properties of two new mixed-valence heptanuclear manganese clusters are described. Both complexes utilize triethanolamine (teaH(3)) as a bridging ligand, displaying near planar, disc-like metal topologies and are of formulae [Mn(II)(4)Mn(IV)(3)(tea)(teaH(2))(3)(peolH)(4)](BF(4))(2).solv (1) and [Mn(II)(4)Mn(III)(3)F(3)(tea)(teaH)(teaH(2))(2)(piv)(4)(Hpiv)(chp)(3)].0.5MeCN (2). Compound 1 is a rare mixed-valence compound containing Mn(II) and Mn(IV) ions only and is the first example of a heptanuclear disc with a {Mn(II)(4)Mn(IV)(3)} oxidation state distribution. Compound 2 is a {Mn(II)(4)Mn(III)(3)} complex and displays a unique arrangement of oxidation states within the disc, when compared to other known {Mn(II)(4)Mn(III)(3)} examples. Variable temperature DC and AC magnetic susceptibility studies were carried out for 1 and 2 in the 2-300 K temperature range. Compound 1 displayed an increase in the chi(M)T susceptibility values as the temperature is decreased indicating dominant ferromagnetic interactions are present within the cluster. Fits of the chi(M)T vs. T data reveals an S = 23/2 ground state, with several close lying excited states within 1 cm(-1). Compound 2 displays an overall decrease in the chi(M)T value as the temperature is decreased down to 2 K indicating dominant antiferromagnetic interactions present with a probable S = 4 ground state as determined from the DC and AC susceptibility data. PMID- 22776899 TI - PAC1 receptor (ADCYAP1R1) genotype is associated with dark-enhanced startle in children. PMID- 22776902 TI - Trauma-induced expression of astrocytic thrombospondin-1 is regulated by P2 receptors coupled to protein kinase cascades. AB - Thrombospondin-1 (TSP-1) is an extracellular matrix protein produced by astrocytes, which can promote synaptogenesis. The regulation of astrocytic TSP-1 involves extracellular ATP through the activation of P2Y receptors coupled to various protein kinase signaling pathways. However, not much is known about the mechanisms regulating TSP-1 expression in primary cortical astrocytes after a traumatic brain injury. Using an in-vitro model of central nervous system trauma that stimulates the release of ATP, we found that trauma-induced expression and release of TSP-1 involved purinergic signaling as both expression and release were significantly attenuated by pyridoxalphosphate-6-azophenyl-2'-4'-disulfonic acid, a P2 receptor antagonist. Further antagonist studies with reactive blue 2 point to a role for P2Y4, as reactive blue 2 is a potent antagonist for rat P2Y4 receptors. In addition, the injury-induced expression of TSP-1 was significantly attenuated by the inhibition of extracellular signal-regulated kinase and p38/mitogen-activated protein kinase, whereas injury-induced release of TSP-1 was significantly blocked by the inhibition of extracellular signal-regulated kinase and Akt. Using an in-vivo model of a moderate parasagittal fluid-percussion brain injury, we found that TSP-1 levels were increased when compared with those in sham animals in the cortex, thalamus, and hippocampus. We conclude that TSP-1 expression after injury can be regulated by the activation of P2 receptors coupled with protein kinase signaling pathways and suggest that purinergic signaling, by regulating TSP expression, may play an important role in cell matrix and cell-cell interactions such as those occurring during central nervous system repair. PMID- 22776900 TI - Disruption of fatty acid amide hydrolase activity prevents the effects of chronic stress on anxiety and amygdalar microstructure. AB - Hyperactivation of the amygdala following chronic stress is believed to be one of the primary mechanisms underlying the increased propensity for anxiety-like behaviors and pathological states; however, the mechanisms by which chronic stress modulates amygdalar function are not well characterized. The aim of the current study was to determine the extent to which the endocannabinoid (eCB) system, which is known to regulate emotional behavior and neuroplasticity, contributes to changes in amygdalar structure and function following chronic stress. To examine the hypothesis, we have exposed C57/Bl6 mice to chronic restraint stress, which results in an increase in fatty acid amide hydrolase (FAAH) activity and a reduction in the concentration of the eCB N arachidonylethanolamine (AEA) within the amygdala. Chronic restraint stress also increased dendritic arborization, complexity and spine density of pyramidal neurons in the basolateral nucleus of the amygdala (BLA) and increased anxiety like behavior in wild-type mice. All of the stress-induced changes in amygdalar structure and function were absent in mice deficient in FAAH. Further, the anti anxiety effect of FAAH deletion was recapitulated in rats treated orally with a novel pharmacological inhibitor of FAAH, JNJ5003 (50 mg per kg per day), during exposure to chronic stress. These studies suggest that FAAH is required for chronic stress to induce hyperactivity and structural remodeling of the amygdala. Collectively, these studies indicate that FAAH-mediated decreases in AEA occur following chronic stress and that this loss of AEA signaling is functionally relevant to the effects of chronic stress. These data support the hypothesis that inhibition of FAAH has therapeutic potential in the treatment of anxiety disorders, possibly by maintaining normal amygdalar function in the face of chronic stress. PMID- 22776901 TI - Reduced cannabinoid CB1 receptor binding in alcohol dependence measured with positron emission tomography. AB - Brain cannabinoid CB1 receptors contribute to alcohol-related behaviors in experimental animals, but their potential role in humans with alcohol dependence is poorly understood. We measured CB1 receptors in alcohol dependent patients in early and protracted abstinence, and in comparison with control subjects without alcohol use disorders, using positron emission tomography and [(18)F]FMPEP-d2, a radioligand for CB1 receptors. We scanned 18 male in-patients with alcohol dependence twice, within 3-7 days of admission from ongoing drinking, and after 2 4 weeks of supervised abstinence. Imaging data were compared with those from 19 age-matched healthy male control subjects. Data were also analyzed for potential influence of a common functional variation (rs2023239) in the CB1 receptor gene (CNR1) that may moderate CB1 receptor density. On the first scan, CB1 receptor binding was 20-30% lower in patients with alcohol dependence than in control subjects in all brain regions and was negatively correlated with years of alcohol abuse. After 2-4 weeks of abstinence, CB1 receptor binding remained similarly reduced in these patients. Irrespective of the diagnostic status, C allele carriers at rs2023239 had higher CB1 receptor binding compared with non-carriers. Alcohol dependence is associated with a widespread reduction of cannabinoid CB1 receptor binding in the human brain and this reduction persists at least 2-4 weeks into abstinence. The correlation of reduced binding with years of alcohol abuse suggests an involvement of CB1 receptors in alcohol dependence in humans. PMID- 22776903 TI - Novel tactile feedback to reduce overt stuttering. AB - Stuttering is generally considered to be a speech disorder that affects ~1% of the global population. Various forms of speech feedback have been shown to reduce overt stuttered speaking, and in particular, second speech signal through speech feedback has drastically reduced utterances of stuttered speech in adults with persistent stuttering. This study reports data for increased overt fluency of speech in an adult stuttering population, whereby the vocalization of the speaker is captured by a microphone or an accelerometer, signal processed, and returned as mechanical tactile speech feedback to the speaker's skin. A repeated measures analysis of variance was used to show that both the microphone and the accelerometer speaking conditions were significantly more fluent than a control (no feedback) condition, with the microphone-driven tactile feedback reducing instances of stuttering by 71% and the accelerometer-driven tactile feedback reducing instances of stuttering by 80%. It is apparent that self-generated tactile feedback can be used to enhance fluency significantly in those who stutter. PMID- 22776904 TI - Amphetamines modulate prefrontal gamma oscillations during attention processing. AB - Amphetamine-based medications robustly suppress symptoms of attention deficit/hyperactivity disorder (ADHD), but their exact mechanisms remain poorly understood. Recent hemodynamic imaging studies have suggested that amphetamines may modulate the prefrontal and anterior cingulate brain regions, although few studies have been published and the results have not been entirely consistent. Meanwhile, several electrophysiological studies have shown that abnormal fast oscillations (in the gamma range) may be closely linked to inattention and other cardinal symptoms of ADHD. In this study, we utilized magnetoencephalography to examine how amphetamines modulate high-frequency brain activity in adults with ADHD. Participants performed an auditory attention task, which required sustained attention in one block and passive listening in a separate block. Participants completed the task twice in the on-medication and off-medication states. All data were analyzed using beamforming techniques to resolve cortical regions showing event-related synchronizations and desynchronizations. Our primary findings indicated that oral administration of amphetamine decreased gamma-band event related desynchronization activity significantly in the medial prefrontal area and decreased event-related synchronization in bilateral superior parietal areas, left inferior parietal, and the left inferior frontal gyrus. These results suggest that psychostimulants strongly modulate gamma activity in frontal and parietal cortical areas, which are known to be central to the brain's core attentional networks. PMID- 22776905 TI - Intracortical convergence of layer 6 neurons. AB - Axonal branches from a subset of neurons in cerebral cortical layer 6 innervate both cortical layer 4 and the thalamus. As such, these neurons are poised to modulate thalamocortical transmission at multiple forebrain sites. Here, we examined the functional organization of the layer 6 intracortical projections in auditory, somatosensory, and visual cortical areas using an optogenetic approach to specifically target these neurons. We characterized the anatomical and physiological organization of these projections using laser-scanning photostimulation to functionally map the elicited postsynaptic responses in layer 4. We found that these responses originated from regions over 1 mm in width, eliciting short-term facilitating responses. These results indicate that intracortical modulation of layer 4 occurs through widespread layer 6 projections in each sensory cortical area. PMID- 22776907 TI - The effects of protection from fishing on species richness: distinguishing between alternative explanations. AB - Marine reserves that prohibit fishing often result in greater densities of individuals and more species than adjacent fished areas. However, simple conclusions about their effects on species richness are confounded, because more species are expected to occur wherever there are more individuals. Here, there is an important distinction between the number of species per sampling unit (species density), and species richness measured as the number of species per given number of individuals. When conservation of species richness is an important goal, analyses need to discriminate between the alternative explanations for differences in the number of species. We used rarefaction to test whether species richness was higher in two 'no-take' marine reserves after controlling for differences in the density of individuals. We surveyed each reserve in three different years. There was a higher density of individuals and species in each reserve than in adjacent fished areas. However, rarefaction analyses indicated that effects on species richness were weak after controlling for the number of individuals: slightly higher species richness was recorded inside each reserve in one of three surveys, but the difference was small, and was apparent only when the maximum number of individuals was approached. Our results therefore indicate that patterns in species density were not reflected by patterns in species richness-the application of rarefaction methods is needed to determine the responses of species richness to protection elsewhere. The distinction between species density and species richness will not be important in all situations, but when it is important, inferences about species richness cannot be reliably deduced from measurements of species density. PMID- 22776906 TI - Inter- and intra-specific patterns of density dependence and population size variability in Salmoniformes. AB - Population dynamics are typically affected by a combination of density independent and density-dependent factors, the latter of which have been conceptually and theoretically linked with how variable population sizes are over time-which in turn has been tied to how prone populations are to extinction. To address evidence for the occurrence of density dependence and its relationship with population size variability (pv), we quantified each of these for 126 populations of 8 species of Salmoniformes. Using random-effects models, we partitioned variation in the strength of density dependence and the magnitude of pv between and within species and estimated the correlation of density dependence and population size variability at both the between- and within-species levels. We found that variation in the strength of density dependence was predominately within species (I(2) = 0.12 [corrected] variation in population size variability was distributed both between and within species (I(2) = 0.40). Contrary to theoretical and conceptual expectations, the strength of density dependence and the magnitude of population size variability were positively correlated at the between species level (r = 0.90), although this estimate had 95 % credibility intervals (Bayesian analogues to confidence intervals) that overlapped zero. The within-species correlation between density dependence and population size variability was not distinguishable from zero. Given that density dependence for Salmoniformes was highly variable within species, we next determined the joint effects of intrinsic (density-dependent) and extrinsic (density-independent) factors on the population dynamics of a threatened salmonid, the Lahontan cutthroat trout (Oncorhynchus clarkii henshawi). We found that density-dependent and -independent factors additively contributed to population dynamics. This finding suggests that the observed within-species variability in density dependence might be attributable to local differences in the strength of density independent factors. PMID- 22776908 TI - A comparative meta-analysis of maximal aerobic metabolism of vertebrates: implications for respiratory and cardiovascular limits to gas exchange. AB - Maximal aerobic metabolic rates (MMR) in vertebrates are supported by increased conductive and diffusive fluxes of O(2) from the environment to the mitochondria necessitating concomitant increases in CO(2) efflux. A question that has received much attention has been which step, respiratory or cardiovascular, provides the principal rate limitation to gas flux at MMR? Limitation analyses have principally focused on O(2) fluxes, though the excess capacity of the lung for O(2) ventilation and diffusion remains unexplained except as a safety factor. Analyses of MMR normally rely upon allometry and temperature to define these factors, but cannot account for much of the variation and often have narrow phylogenetic breadth. The unique aspect of our comparative approach was to use an interclass meta-analysis to examine cardio-respiratory variables during the increase from resting metabolic rate to MMR among vertebrates from fish to mammals, independent of allometry and phylogeny. Common patterns at MMR indicate universal principles governing O(2) and CO(2) transport in vertebrate cardiovascular and respiratory systems, despite the varied modes of activities (swimming, running, flying), different cardio-respiratory architecture, and vastly different rates of metabolism (endothermy vs. ectothermy). Our meta analysis supports previous studies indicating a cardiovascular limit to maximal O(2) transport and also implicates a respiratory system limit to maximal CO(2) efflux, especially in ectotherms. Thus, natural selection would operate on the respiratory system to enhance maximal CO(2) excretion and the cardiovascular system to enhance maximal O(2) uptake. This provides a possible evolutionary explanation for the conundrum of why the respiratory system appears functionally over-designed from an O(2) perspective, a unique insight from previous work focused solely on O(2) fluxes. The results suggest a common gas transport blueprint, or Bauplan, in the vertebrate clade. PMID- 22776909 TI - Lateral migration and focusing of colloidal particles and DNA molecules under viscoelastic flow. AB - Much difficulty has been encountered in manipulating small-scale materials, such as submicron colloidal particles and macromolecules (e.g., DNA and proteins), in microfluidic devices since diffusion processes due to thermal (Brownian) motion become more pronounced with decreasing particle size. Here, we present a novel approach for the continuous focusing of such small-scale materials. First, we successfully focused fluorescent submicron polystyrene (PS) beads along equilibrium positions in microchannels through the addition of a small amount water-soluble polymer [500 ppm poly(ethylene oxide) (PEO)]. Lateral migration velocity significantly depends upon the viscoelastic effect (Weissenberg number: Wi) and the aspect ratio of particle size to channel height (a/h). Interestingly, focusing using viscoelastic flows was also observed for flexible DNA molecules (lambda-DNA and T4-DNA), which have radii of gyration (R(g)) of approximately 0.69 MUm and 1.5 MUm, respectively. This small-scale material manipulation using medium viscoelasticity will contribute to the design of nanoparticle separation and genomic mapping devices. PMID- 22776911 TI - Depressive-like behavior in adolescents after maternal separation: sex differences, controllability, and GABA. AB - Exposure to adversity during development is an identified risk factor for depression later in life. In humans, early adversity accelerates the onset of depressive symptoms, which manifest during adolescence. Animal studies have used maternal separation as a model of early adversity to produce adult depressive like behaviors, but have yet to examine these behaviors during adolescence. Moreover, the nature of depressive-like behaviors has not been well characterized in this model. Here, we used the triadic model of learned helplessness to understand controllability, helplessness, and motivational factors following maternal separation in male and female adolescent rats. We found sex-dependent changes in the effects of separation, with males demonstrating loss of controllability in an escapable shock condition, whereas females demonstrated motivational impairment in a no-shock condition. The effect, however, did not endure as adult females were no longer helpless. Reductions in parvalbumin, a GABAergic marker, in the prefrontal cortex of separated subjects relative to age matched controls were evident and paralleled depressive-like behavior. Understanding the risk factors for depression, the nature of depressive-like behaviors, and their unique sex dependency may ultimately provide insight into improved treatments. PMID- 22776912 TI - A comparative study of histopathological analysis of filum terminale in patients with tethered cord syndrome and in normal human fetuses. AB - BACKGROUND: The structural changes in filum terminale (FT) may be responsible for tethered cord syndrome (TCS) in children. Although the histological changes in FT related to TCS are well-known, there is no comparative study of the changes which occur in TCS and normal fetal FT samples. The aims of this study are to compare the histological changes which occurred in FT samples of TCS and in fetuses, and to point out these changes. METHODS: During the last 2 years, 14 cases of TCS were operated on, the FT was cut and the spinal cord was released. Among them, 6 samples of FT were obtained for histopathological examination. Moreover, 1 FT from an adult cadaver and 4 samples from fetal FT were obtained for the same examination. RESULTS: While adipose tissue, fibrosis, hyalinization, and meningothelial proliferation were observed in FT samples of TCS, none of these findings were observed in fetal samples. Elastic fibers were present in all TCS specimens and the adult cadaver, but were not observed in fetuses. Peripheral nerves, ganglion cells and ependymal cells were observed in fetal FT samples. CONCLUSION: These changes probably begin at birth. PMID- 22776913 TI - Dementia resulting from traumatic brain injury: what is the pathology? AB - Traumatic brain injury (TBI) is among the earliest illnesses described in human history and remains a major source of morbidity and mortality in the modern era. It is estimated that 2% of the US population lives with long-term disabilities due to a prior TBI, and incidence and prevalence rates are even higher in developing countries. One of the most feared long-term consequences of TBIs is dementia, as multiple epidemiologic studies show that experiencing a TBI in early or midlife is associated with an increased risk of dementia in late life. The best data indicate that moderate and severe TBIs increase risk of dementia between 2- and 4-fold. It is less clear whether mild TBIs such as brief concussions result in increased dementia risk, in part because mild head injuries are often not well documented and retrospective studies have recall bias. However, it has been observed for many years that multiple mild TBIs as experienced by professional boxers are associated with a high risk of chronic traumatic encephalopathy (CTE), a type of dementia with distinctive clinical and pathologic features. The recent recognition that CTE is common in retired professional football and hockey players has rekindled interest in this condition, as has the recognition that military personnel also experience high rates of mild TBIs and may have a similar syndrome. It is presently unknown whether dementia in TBI survivors is pathophysiologically similar to Alzheimer disease, CTE, or some other entity. Such information is critical for developing preventive and treatment strategies for a common cause of acquired dementia. Herein, we will review the epidemiologic data linking TBI and dementia, existing clinical and pathologic data, and will identify areas where future research is needed. PMID- 22776914 TI - Dynamics of MRSA carriage in veal calves: a longitudinal field study. AB - Colonization of Methicillin-Resistant Staphylococcus aureus (MRSA) in food producing animals has public health implications, but intervention targets have not yet been identified. In this field study occurrence and dynamics of MRSA in veal calves were investigated longitudinally on three farms. Determinants generally associated with MRSA carriage, such as environmental exposure and antimicrobial use, were explored. In addition, the reliability and reproducibility of MRSA detection in nasal samples from veal calves were investigated as well as the additional value of rectal samples to establish MRSA status of an individual animal. On these three farms, MRSA prevalence and MRSA air loads in stables rapidly increased during the production cycle, especially after releasing calves from their individual houses, but not simultaneously with or directly after treatment with antimicrobials. These observations constitute the hypothesis that antimicrobial use may not necessarily be the only condition for MRSA transmission in veal calves, but indicate that other factors may contribute to transmission as well. MRSA in calves was present both nasally and rectally. The reproducibility and repeatability of the nasal samples were moderate. The results of this study give a better understanding of the dynamics of MRSA in a field situation. PMID- 22776915 TI - The tall cell variant of papillary thyroid carcinoma: clinical and pathological features and outcomes. AB - BACKGROUND: The tall cell variant (TCV) is a relatively rare variant of papillary thyroid cancer. Since a controversy exists whether or not the TCV has a worse outcome, the aim of our study was to retrospectively compare the clinicopathological features and outcomes in a group of TCV patients and a larger group of patients with classical papillary thyroid carcinoma (cPTC). SUBJECTS AND METHODS: Data from 30 TCV and 293 cPTC patients were analyzed. Among the 293 cPTC, we also selected a "high-risk" cPTC group (no.=103) that was treated with the same protocol used for the TCV patients. All data were managed by Cox analysis. RESULTS: Compared to all cPTC patients, TCV subjects displayed only a significantly higher rate of extrathyroid extension. At multivariate analysis, TCV was not an independent variable for the prediction of a high risk of persistent/recurrent disease. At the last follow-up observation, there was no difference in the disease status between the TCV and all cPTC patients. Moreover, "high-risk" cPTC patients had a significant increase in persistent/recurrent disease. CONCLUSIONS: In our study, although the TCV histotype is associated with a higher prevalence of extrathyroid extension, it is characterized by an outcome that is not significantly different from that of all cPTC patients and is more favorable than that of "high-risk" cPTC patients. Only those TCV patients classified as "high risk" based on specific pathological and clinical features, according to current guidelines, should be treated aggressively, such as with a total thyroidectomy, neck lymph node dissection or ablative radioiodine treatment. PMID- 22776916 TI - ACS chemical neuroscience molecule spotlight on Saredutant. AB - Saredutant (SR48968), a potentially novel treatment option for major depressive disorders (MDD) and generalized anxiety disorder (GAD), is a drug from Sanofi Aventis currently in phase III clinical trials. MDD is a common mental disorder that affects 121 million people worldwide, nearly 4% of the adult population (www.who.int/mental_health/management/depression/definition/en/). MDD continues to be one of the leading causes of disability with more than three quarters of the diagnosed cases having effective treatments available (www.who.int/mental_health/management/depression/definition/en/). However, even though MDD affects a large portion of the population, effective treatment options with low incidence of adverse events remain a major concern for the pharmaceutical industry. Adverse events (GI side effects1, weight gain, somnolence/insomnia, etc. (Demyttenaere K. (2003) Risk factors and predictors of compliance in depressionEur. Neuropshychopharm.13S69-S75)) from the typical treatments remain the major reason for premature stopping or poor compliance of treatment. New treatments to the market must bear in mind these adverse events, and the pharmaceutical industry is currently looking for drugs with new mechanisms of action and those that are better tolerated. PMID- 22776917 TI - Molecular phylogeny of Anaphalis (Asteraceae, Gnaphalieae) with biogeographic implications in the Northern Hemisphere. AB - Anaphalis is the largest Asian genus in the tribe Gnaphalieae (Asteraceae) and has its greatest species diversity in the eastern Himalayas. The nuclear internal and external transcribed spacers were sequenced for Anaphalis species, with an emphasis on the eastern Himalayan taxa to examine the monophyly and construct the phylogenetic relationships of and within the genus. The results suggest that all species of Anaphalis are nested with Helichrysum, showing a close relationship with a Mediterranean-Asian group of Helichrysum. Although the monophyly of Anaphalis is only weakly supported, two clades within the genus are well recognized, each consisting of two subgroups. The inferred phylogenetic relationships within Anaphalis correspond to the shape of leaf base, rather than the morphology of the capitula and phyllaries that are usually used for species delimitation and classification in the genus. All four subgroups of Anaphalis are common and diversified in the eastern Himalayas with multiple dispersals out of this region. The sole North American species of Anaphalis is best hypothesized to be the result of long-distance dispersal or overland migration via Bering land bridge from Asia. Our analyses suggest that the extant distribution of Anaphalis has most likely resulted one radiation into the eastern Himalayas followed by repeated independent dispersals and/or radiations mostly into eastern Asia but also into the western Himalayas, North America, and southeast Asia. PMID- 22776919 TI - Longitudinal structure-function relationships with scanning laser ophthalmoscopy and standard achromatic perimetry. AB - OBJECTIVE: To explore longitudinal correlations between structural and functional rates of glaucoma progression with confocal scanning laser ophthalmoscopy and standard achromatic perimetry. METHODS: In this retrospective longitudinal study, 108 eyes with suspected or established glaucoma and 5 or more good-quality scanning laser ophthalmoscopy examinations (global pixel SD<50 MUm) and 6 or more reliable visual field (VF) examinations were included. Global and regional rates of progression for VF sensitivity and rim area (RA) were calculated with linear regression analysis. Correlations of global and regional rates of progression were calculated with bivariate correlation analyses. Linear mixed models were built to determine predictive factors for functional and structural changes over time. RESULTS: The mean (SD) baseline mean deviation was -4.6 (4.9) decibels. The inferotemporal and superotemporal RAs had the highest overall rates of decay (0.0018 mm2/y). Glaucoma progressed in 38 (35.2%) and 20 (18.5%) eyes based on event and trend mean deviation criteria, respectively. The highest correlations of rates were observed between the superonasal or superotemporal RA and inferior VF clusters (rho=0.25-0.39; P<=.03). Follow-up time, baseline RA, and their interaction were the only significant predictors for RA change; belonging to the group with progression was not associated with higher rates of RA progression. CONCLUSIONS: Longitudinal structure-function relationships are fair at best in eyes with suspected or established glaucoma. Eyes with progressing disease according to VF criteria do not show significantly higher rates of RA progression. Both structural and functional outcomes need to be monitored to detect glaucoma progression in a timely manner. PMID- 22776921 TI - Enhanced depth imaging optical coherence tomography of small choroidal melanoma: comparison with choroidal nevus. AB - OBJECTIVE: To evaluate characteristics of small choroidal melanoma using enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT). DESIGN: Retrospective comparative analysis. RESULTS: Of 37 eyes with small choroidal melanoma imaged using EDI-OCT, the mean tumor thickness was 1025 MUm by EDI-OCT compared with 2300 MUm by ultrasonography. By EDI-OCT, choroidal features included optical shadowing in 36 (100%) and overlying choriocapillaris thinning in 37 (100%). Outer retinal features included shaggy photoreceptors in 18 (49%), as well as absence (structural loss) of photoreceptors in 9 (24%), inner segment outer segment junction in 24 (65%), external limiting membrane in 16 (43%), outer nuclear layer in 6 (16%), and outer plexiform layer in 4 (11%). Inner retinal features included irregularity of inner nuclear layer in 3 (8%), inner plexiform layer in 3 (8%), ganglion cell layer in 3 (8%), and nerve fiber layer in 2 (5%). Also identified were subretinal fluid in 34 (92%), subretinal lipofuscin deposition in 35 (95%), and intraretinal edema in 6 (16%). Using EDI-OCT, a comparison with similar-sized choroidal nevus revealed that small choroidal melanoma showed increased tumor thickness, subretinal fluid, subretinal lipofuscin deposition, and retinal pigment epithelium atrophy. Statistically significant EDI-OCT features for small choroidal melanoma included intraretinal edema (P=.003), shaggy photoreceptors or loss of photoreceptors (P=.005), loss of external limiting membrane (P=.008), loss of inner segment-outer segment junction (P=.02), irregularity of inner plexiform layer (P=.04), and irregularity of ganglion cell layer (P=.04) (t test and chi2 test). Shaggy photoreceptors were found overlying small choroidal melanoma in 18 (49%) but were not observed overlying choroidal nevus (P<.001). CONCLUSIONS: Small choroidal melanoma tumor thickness was overestimated by 55% on ultrasonography compared with EDI-OCT. The EDI-OCT features of small choroidal melanoma compared with choroidal nevus include increased tumor thickness, subretinal fluid, subretinal lipofuscin deposition, and retinal irregularities, including shaggy photoreceptors. PMID- 22776923 TI - Treatment of optic neuritis by plasma exchange (add-on) in neuromyelitis optica. AB - OBJECTIVE: To assess the contribution of plasma exchange (PE) in association (add on) with pulsed intravenous corticosteroids in acute optic neuritis of neuromyelitis optica (NMO) and limited forms of NMO. METHODS: Thirty-six patients with optic neuritis were treated from January 1, 1995, through December 31, 2010, with pulsed intravenous corticosteroids and 16 with pulsed intravenous corticosteroids plus PE. The ophthalmologic examination was performed at least 6 months after optic neuritis treatment. Visual acuity and visual field assessed with the Snellen scale and the logarithmic scale of the Early Treatment Diabetic Retinopathy Study were measured using standard automated perimetry and frequency doubling technology perimetry. Retinal peripapillary fiber thickness was measured using optical coherence tomography. RESULTS: Final visual acuity was 20/400 in the corticosteroid group and 20/50 in the PE group (P=.04). The gain in visual acuity was 20/200 in the corticosteroid group and 20/30 in the PE group (P=.01). A poor final visual acuity outcome (<=20/200) was found in 19 of 36 patients (53%) in the corticosteroid group and 2 of 16 patients (13%) in the PE group (P=.008). Mean (SD) thickness of peripapillary retinal nervous fibers was 63.1 (20.4) MUm in the corticosteroid group and 70.3 (20.3) MUm in the PE group (P=.16). The mean (SD) thickness in the temporal quadrant was 38.5 (14.1) MUm in the corticosteroid group and 44.5 (12.7) MUm in the PE group (P=.02). In multivariate analysis, PE treatment was the only independent factor associated with a visual acuity greater than 20/200. CONCLUSION: In optic neuritis associated with NMO, sequential treatment with pulsed intravenous corticosteroids and PE is more effective than standard monotherapy with corticosteroids on visual acuity outcome. PMID- 22776920 TI - Understanding disparities among diagnostic technologies in glaucoma. AB - OBJECTIVE: To investigate causes of disagreement among 3 glaucoma diagnostic techniques: standard automated achromatic perimetry (SAP), the multifocal visual evoked potential technique (mfVEP), and optical coherence tomography (OCT). METHODS: In a prospective cross-sectional study, 138 eyes of 69 patients with glaucomatous optic neuropathy were tested using SAP, the mfVEP, and OCT. Eyes with the worse and better mean deviations (MDs) were analyzed separately. If the results of 2 tests were consistent for the presence of an abnormality in the same topographic site, that abnormality was considered a true glaucoma defect. If a third test missed that abnormality (false-negative result), the reasons for disparity were investigated. RESULTS: Eyes with worse MD (mean [SD], -6.8 [8.0] dB) had better agreements among tests than did eyes with better MD (-2.5 [3.5] dB, P<.01). For the 94 of 138 hemifields with abnormalities of the more advanced eyes, the 3 tests were consistent in showing the same hemifield abnormality in 50 hemifields (53%), and at least 2 tests were abnormal in 65 of the 94 hemifields (69%). The potential explanations for the false-negative results fell into 2 general categories: inherent limitations of each technique to detect distinct features of glaucoma and individual variability and the distribution of normative values used to define statistically significant abnormalities. CONCLUSIONS: All the cases of disparity could be explained by known limitations of each technique and interindividual variability, suggesting that the agreement among diagnostic tests may be better than summary statistics suggest and that disagreements between tests do not indicate discordance in the structure-function relationship. PMID- 22776924 TI - Bilateral sequential nonarteritic anterior ischemic optic neuropathy: a comparison of visual outcomes in fellow eyes using quantitative analysis of goldmann visual fields. AB - OBJECTIVE: To better define the concordance of visual loss in patients with nonarteritic anterior ischemic optic neuropathy (NAION). METHODS: The medical records of 86 patients with bilateral sequential NAION were reviewed retrospectively, and visual function was assessed using visual acuity, Goldmann visual fields, color vision, and relative afferent papillary defect. A quantitative total visual field score and score per quadrant were analyzed for each eye using the numerical Goldmann visual field scoring method. RESULTS: Outcome measures were visual acuity, visual field, color vision, and relative afferent papillary defect. A statistically significant correlation was found between fellow eyes for multiple parameters, including logMAR visual acuity (P=.01), global visual field (P<.001), superior visual field (P<.001), and inferior visual field (P<.001). The mean deviation of total (P<.001) and pattern (P<.001) deviation analyses was significantly less between fellow eyes than between first and second eyes of different patients. CONCLUSIONS: Visual function between fellow eyes showed a fair to moderate correlation that was statistically significant. The pattern of vision loss was also more similar in fellow eyes than between eyes of different patients. These results may help allow better prediction of visual outcome for the second eye in patients with NAION. PMID- 22776925 TI - Ciliary body medulloepithelioma in a 10-year-old boy. PMID- 22776926 TI - Risk for retinal detachment after phacoemulsification: a whole-population study of cataract surgery outcomes. AB - OBJECTIVES: To estimate the long-term cumulative incidence of and risk factors for retinal detachment (RD) after phacoemulsification using linked administrative medical data. METHODS: We used the Western Australian Data Linkage System to identify patients who underwent phacoemulsification in Western Australia between January 1989 and December 2001. Retinal detachment cases were those patients requiring admission for RD surgery after phacoemulsification that were validated by medical record review. Kaplan-Meier analysis was used to calculate a cumulative incidence. Cox proportional hazards regression modeling was used to determine the association between RD and risk factors, including patient demographics and operative and hospital factors. Some important risk factors, including axial length and Nd:YAG laser capsulotomy, were not examined. RESULTS: We identified 237 RD cases following 65 055 phacoemulsification procedures, with a 10-year cumulative incidence of 0.68% (95% CI, 0.56%-0.83%). Significant risk factors were year of surgery (hazard ratio [HR], 0.43; 95% CI, 0.28-0.66 [1999 2001 compared with 1989-1993] for each 5-year period after 1985), age younger than 60 years (3.76; 2.83-5.00), male sex (1.91; 1.45-2.51), and anterior vitrectomy (27.60; 19.27-39.52). Hospital location, patient rural or remote locality, hospital cataract surgery volume, failed intraocular lens insertion, length of stay, and patient insurance status were not significantly associated with RD. CONCLUSIONS: Risk for RD after phacoemulsification has almost halved for each 5-year period since its adoption in the mid 1980s. Younger patient age and male sex at surgery significantly increased risk for RD. Phacoemulsification requiring anterior vitrectomy vastly increased risk for RD. PMID- 22776927 TI - Incidence and clinical characteristics of periocular infantile hemangiomas. AB - OBJECTIVE: To report the incidence, demographics, and clinical findings among a population-based cohort of children with periocular infantile hemangiomas. METHODS: The medical records of all patients (<19 years of age) diagnosed as having periocular infantile hemangiomas while residing in Olmsted County, Minnesota, from January 1, 1965, through December 31, 2004, were retrospectively reviewed. RESULTS: Forty-three children were diagnosed as having periocular infantile hemangiomas during the 40-year period, yielding an incidence of 5.4 per 100,000 individuals younger than 19 years (95% CI, 3.8-7.1) or a birth prevalence of 1 in 1586 live births. Thirty children (70%) were female (P<.001). There was a history of maternal infertility in approximately 1 in 5 children and premature birth in 1 in 8 children. Twenty-six children (61%) had other abnormalities, including secondary hemangiomas in 9 (21%). Forty-one patients (95%) had unilateral disease, and 37 hemangiomas (86%) were located on the upper eyelid. CONCLUSIONS: In this population-based study, periocular infantile hemangiomas occurred in 1 in 1586 live births and were most prevalent on the unilateral upper eyelid of white female patients. Prevalent associations included maternal infertility and premature birth. Other abnormalities, including secondary hemangiomas in 1 in 5 children, were common in this cohort. PMID- 22776929 TI - Cotton-wool spot and optical coherence tomography of a retinal nerve fiber layer defect. PMID- 22776928 TI - Combined posterior chamber intraocular lens, vitrectomy, Retisert, and pars plana tube in noninfectious uveitis. AB - OBJECTIVE: To assess the safety and efficacy of combined cataract extraction, posterior chamber intraocular lens placement, pars plana vitrectomy, fluocinolone acetonide intravitreal implant (Retisert), and Ahmed valves with pars plana tube (CPR-PT) in eyes with chronic, posterior, noninfectious uveitis. METHODS: Retrospective study of patients who underwent CPR-PT. Outcome measures included visual acuity, intraocular pressure, inflammation, and complications. RESULTS: Eight eyes were included, with a mean follow-up of 18 months. Mean visual acuity improved from 1.89 to 0.14 logMAR (Snellen, counting fingers at 2 ft [0.6 m]) to 20/30; P=.01). Mean intraocular pressure remained stable at 16 to 17 mm Hg (P=.35). The number of glaucoma medications per eye decreased from 2.9 to 0.25 (P=.01). Systemic prednisone therapy was discontinued in all patients by 9 months postoperatively. Inflammation was well controlled in all eyes. CONCLUSION: The CPR-PT procedure allows rapid visual rehabilitation without major short-term complications. PMID- 22776930 TI - February 2012 archives web quiz winner. Answer: Shaken baby syndrome/nonaccidental injury. PMID- 22776931 TI - Patient consent for resident involvement in surgical care. PMID- 22776932 TI - On seeing yellow: the case for, and against, short-wavelength light-absorbing intraocular lenses. AB - The normal human crystalline lens absorbs UV and short-wavelength visible electromagnetic radiation. Early intraocular lenses (IOLs) permitted the transmission of such radiation to the retina following cataract extraction. Experimental studies of the absorption profile of the crystalline lens and animal studies demonstrating the deleterious effects of short-wavelength radiation on the retina led to the development of UV-absorbing, and later, short-wavelength light-absorbing (SLA) IOLs. Short-wavelength light-absorbing IOLs were designed to mimic the absorption properties of the normal crystalline lens by absorbing some short-wavelength light in addition to UV radiation; however, debate continues regarding the relative merits of such lenses over UV-absorbing IOLs. Advocates of SLA IOLs suggest that they may theoretically offer increased photoprotection and decreased glare sensitivity and draw on in vitro, animal, and limited clinical studies that infer possible benefits. Detractors suggest that there is no direct evidence supporting a role for SLA IOLs in preventing retinal dysfunction in humans and suggest that they may have negative effects on color perception, scotopic vision, and circadian rhythms. This article examines the theoretical and empirical evidence for, and against, such lenses. PMID- 22776933 TI - Corneal edema after descemet membrane stripping automated endothelial keratoplasty with the use of gentian violet staining. PMID- 22776934 TI - Lagophthalmos in severe anorexia nervosa: a case series. PMID- 22776935 TI - Bevacizumab therapy for tamoxifen-induced crystalline retinopathy and severe cystoid macular edema. PMID- 22776936 TI - Disclosure of resident involvement in ophthalmic surgery. PMID- 22776937 TI - Intravitreal bevacizumab in advanced-stage neovascular age-related macular degeneration with visual acuity lower than 20/200. PMID- 22776938 TI - Mortality from cerebral vasculitis associated with rapid steroid taper during treatment of acute posterior multifocal placoid pigment epitheliopathy. PMID- 22776939 TI - Orange pigment sediment overlying small choroidal melanoma. PMID- 22776940 TI - Nonmydriatic digital ocular fundus photography on the iPhone 3G: the FOTO-ED study. PMID- 22776941 TI - Intravitreal daptomycin in a case of bilateral endogenous endophthalmitis. PMID- 22776942 TI - Conjunctival pediatric follicular lymphoma. PMID- 22776943 TI - Rate of amblyopia in periocular infantile hemangiomas. PMID- 22776944 TI - Penetrating ocular trauma from airsoft gun. PMID- 22776945 TI - Refractive outcomes for toric intraocular lenses. PMID- 22776946 TI - Exact toric intraocular lens calculations using currently available lens constants. PMID- 22776947 TI - Toric intraocular lens calculations. PMID- 22776949 TI - Discussion of changes in intraocular pressure and anterior segment morphometry following phacoemulsification cataract surgery. PMID- 22776951 TI - Obviating endophthalmitis after cataract surgery: the role of the paracentesis. PMID- 22776953 TI - Talking to patients. PMID- 22776955 TI - In vitro evaluation of major in vivo drug metabolic pathways using primary human hepatocytes and HepaRG cells in suspension and a dynamic three-dimensional bioreactor system. AB - Major human specific metabolites, not detected during in vivo and in vitro preclinical studies, may cause unexpected drug interactions and toxicity in human and delays in clinical programs. Thus, reliable preclinical tools for the detection of major human metabolites are of high importance. The aim of this study was to compare major drug metabolic pathways in HepaRG cells, a human hepatoma cell line, to fresh human hepatocytes, cryopreserved human hepatocytes, and human in vivo data. Furthermore, the maintenance of cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT) activities in a dynamic three-dimensional (3D) bioreactor were evaluated over time by using HepaRG cells and human hepatocytes. (14)C-diclofenac and a candidate from AstraZeneca's drug development program, (14)C-AZD6610, which are metabolized by P450 and UGT in vivo, were used as model substrates. The proportion of relevant biotransformation pathways of the investigated drug was clearly different in the various cell systems. The hydroxylation route was favored in primary human hepatocytes, whereas the glucuronidation route was favored in HepaRG cells. The human in vivo metabolite profile of AZD6610 was best represented by human hepatocytes, whereas all major diclofenac metabolites were detected in HepaRG cells. Moreover, the metabolite profiles in cryopreserved and fresh human hepatocytes were essentially the same. The liver bioreactor using both fresh human hepatocytes and HepaRG cells retained biotransformation capacity over 1 week. Thus, the incubation time can be increased from a few hours in suspension to several days in 3D cultures, which opens up for detection of metabolites from slowly metabolized drugs. PMID- 22776957 TI - High-performance liquid chromatographic analysis of as-synthesised N,N' dimethylformamide-stabilised gold nanoclusters product. AB - Reverse-phase high-performance liquid chromatographic (RP-HPLC) separation and analysis of polydisperse water-soluble gold nanoclusters (AuNCs) stabilised with N,N'-dimethylformamide (DMF) were investigated. Under optimal elution gradient conditions, the separation of DMF-AuNCs was monitored by absorption and fluorescence spectroscopy. The UV-vis spectral characteristics of the separated DMF-AuNCs have been captured and they do not possess distinct surface plasmon resonance bands, indicating that all DMF-AuNCs are small AuNCs. The photoluminescence emission spectra of the separated DMF-AuNCs are in the blue light region. Moreover, cationic DMF-AuNCs are for the first time identified by ion chromatography. Our proposed RP-HPLC methodology has been successfully applied to separate AuNCs of various Au atoms as well as DMF-stabilised ligands. Finally, the composition of the separated DMF-AuNCs was confirmed by matrix assisted laser desorption/ionisation time-of-flight mass spectrometry and electrospray ionisation mass spectrometry, proving that the as-synthesised DMF AuNCs product consists of Au10+, Au10, Au11, Au12, Au13, and Au14 NCs stabilised with various numbers of DMF ligands. PMID- 22776956 TI - Cannabinoid receptor activation correlates with the proapoptotic action of the beta2-adrenergic agonist (R,R')-4-methoxy-1-naphthylfenoterol in HepG2 hepatocarcinoma cells. AB - Inhibition of cell proliferation by fenoterol and fenoterol derivatives in 1321N1 astrocytoma cells is consistent with beta(2)-adrenergic receptor (beta(2)-AR) stimulation. However, the events that result in fenoterol-mediated control of cell proliferation in other cell types are not clear. Here, we compare the effect of the beta(2)-AR agonists (R,R')-fenoterol (Fen) and (R,R')-4-methoxy-1 naphthylfenoterol (MNF) on signaling and cell proliferation in HepG2 hepatocarcinoma cells by using Western blotting and [(3)H]thymidine incorporation assays. Despite the expression of beta(2)-AR, no cAMP accumulation was observed when cells were stimulated with isoproterenol or Fen, although the treatment elicited both mitogen-activated protein kinase and phosphatidylinositol 3 kinase/Akt activation. Unexpectedly, isoproterenol and Fen promoted HepG2 cell growth, but MNF reduced proliferation together with increased apoptosis. The mitogenic responses of Fen were attenuated by 3-(isopropylamino)-1-[(7-methyl-4 indanyl)oxy]butan-2-ol (ICI 118,551), a beta(2)-AR antagonist, whereas those of MNF were unaffected. Because of the coexpression of beta(2)-AR and cannabinoid receptors (CBRs) and their impact on HepG2 cell proliferation, these Galpha(i)/Galpha(o)-linked receptors may be implicated in MNF signaling. Cell treatment with (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3 de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone (WIN 55,212-2), a synthetic agonist of CB(1)R and CB(2)R, led to growth inhibition, whereas inverse agonists of these receptors blocked MNF mitogenic responses without affecting Fen signaling. MNF responses were sensitive to pertussis toxin. The beta(2)-AR deficient U87MG cells were refractory to Fen, but responsive to the antiproliferative actions of MNF and WIN 55,212-2. The data indicate that the presence of the naphthyl moiety in MNF results in functional coupling to the CBR pathway, providing one of the first examples of a dually acting beta(2)-AR-CBR ligand. PMID- 22776958 TI - Urinary erythropoietin concentrations after early short-term infusion of high dose recombinant epo for neuroprotection in preterm neonates. AB - BACKGROUND: High-dose recombinant human erythropoietin (rEpo) has first been administered in clinical trials for neuroprotection in very preterm neonates at high risk of brain injury and in (near-) term neonates with hypoxic-ischemic encephalopathy. However, recent trials in adults raised concerns about the safety of high-dose rEpo for neuro- and cardioprotection. OBJECTIVES: To evaluate the putative accumulation or renal leakage of Epo as a function of developmental stage after repetitive early short-term infusion of high-dose rEpo (3 * 3,000 U/kg within 42 h after birth; NCT00413946) for neuroprotection in very preterm infants. METHODS: Epo concentrations were measured using the ELISA technique in the first two consecutive urine specimens after each rEpo infusion. RESULTS: Renal Epo excretion was significantly higher in preterm infants with gestational ages <29 weeks than in more mature infants and reached up to 23% of the administered rEpo within 8 h after each infusion. The urinary Epo concentration did not increase after three repetitive infusions of high-dose rEpo. The ratio of urinary Epo to total protein concentrations was the same in infants with gestational ages <29 weeks and in those with gestational ages >=29 weeks. CONCLUSIONS: Our data suggest that the higher renal Epo excretion in more immature infants may be attributed to a higher glomerular filtration leakage due to the lower maturation of the kidneys and argue against saturation kinetics after multiple doses of 3,000 U/kg rEpo. This information should be considered in future trials on the use of rEpo for neuroprotection in neonates. PMID- 22776960 TI - Self-assembly of block copolymers. AB - Block copolymer (BCP) self-assembly has attracted considerable attention for many decades because it can yield ordered structures in a wide range of morphologies, including spheres, cylinders, bicontinuous structures, lamellae, vesicles, and many other complex or hierarchical assemblies. These aggregates provide potential or practical applications in many fields. The present tutorial review introduces the primary principles of BCP self-assembly in bulk and in solution, by describing experiments, theories, accessible morphologies and morphological transitions, factors affecting the morphology, thermodynamics and kinetics, among others. As one specific example at a more advanced level, BCP vesicles (polymersomes) and their potential applications are discussed in some detail. PMID- 22776961 TI - Germline BRCA1 and BRCA2 mutations in ovarian cancer: utility of a histology based referral strategy. AB - OBJECTIVE: To estimate the frequency of BRCA1 and BRCA2 germline mutations in women with nonmucinous epithelial ovarian carcinoma unselected for a family history of breast or ovarian cancer. METHODS: From 2004 to 2009, women undergoing surgical staging for nonmucinous epithelial ovarian carcinoma, including fallopian tube and primary peritoneal carcinoma, were invited to participate in tumor banking and genetic counseling for BRCA1 and BRCA2 mutations. Pathology and family history obtained by the gynecologic oncology surgeon and genetic counselors were reviewed. RESULTS: Of 131 women fulfilling entry criteria, germline BRCA1 and BRCA2 mutations were found in 20% (26/131) and were exclusively associated with high-grade serous histology (26/103 [25%]). Restricting BRCA1 and BRCA2 testing to women with family histories of hereditary breast and ovarian cancer, as ascertained by the surgeon, missed 14 mutation carriers, lowering detection rates to 9% (12/131) or 11.6% (12/103) if only considering the patients with high-grade serous histology. This improved to 16% (21/131) or 20.4% (21/103) when ascertained by the genetic counselor; however, 5 of 26 (19%) mutation carriers did not have a family history of hereditary breast or ovarian cancer. CONCLUSION: Germline BRCA1 and BRCA2 mutations in ovarian (pelvic) cancer are associated with high-grade serous histology. The high incidence (25%) of germline BRCA1 and BRCA2 mutations specific to the high-grade serous subtype suggests that genetic assessment of all women diagnosed with high grade serous ovarian (pelvic) carcinoma will improve detection rates and capture mutation carriers otherwise missed by referral based on family history alone. LEVEL OF EVIDENCE: II. PMID- 22776959 TI - Retargeting sleeping beauty transposon insertions by engineered zinc finger DNA binding domains. AB - The Sleeping Beauty (SB) transposon is a nonviral, integrating vector system with proven efficacy in preclinical animal models, and thus holds promise for future clinical applications. However, SB has a close-to-random insertion profile that could lead to genotoxic effects, thereby presenting a potential safety issue. We evaluated zinc finger (ZF) DNA-binding domains (DBDs) for their abilities to introduce a bias into SB's insertion profile. E2C, that binds a unique site in the erbB-2 gene, mediated locus-specific transposon insertions at low frequencies. A novel ZF targeting LINE1 repeats, ZF-B, showed specific binding to an 18-bp site represented by ~12,000 copies in the human genome. We mapped SB insertions using linear-amplification (LAM)-PCR and Illumina sequencing. Targeted insertions with ZF-B peaked at approximately fourfold enrichment of transposition around ZF-B binding sites yielding ~45% overall frequency of insertion into LINE1. A decrease in the ZF-B dataset with respect to transposon insertions in genes was found, suggesting that LINE1 repeats act as a sponge that "soak up" a fraction of SB insertions and thereby redirect them away from genes. Improvements in ZF technology and a careful choice of targeted genomic regions may improve the safety profile of SB for future clinical applications. PMID- 22776962 TI - Noninvasive single-exon fetal RHD determination in a routine screening program in early pregnancy. AB - OBJECTIVE: To develop a simple and robust assay suitable for fetal RHD screening in first-trimester pregnancy and to estimate the sensitivity and specificity of the test after its implementation in an unselected pregnant population. METHODS: Pregnant women attending their first antenatal visit were included, and fetal RHD determination was performed for all women who typed RhD-negative by routine serology. DNA was extracted by an automated system and quantitative polymerase chain reaction was done by an assay based on exon 4. Reporting criteria were simple and strict. RESULTS: Four thousand one hundred eighteen pregnancies, with a median gestational age of 10 weeks, were included. After 211 (5.1%) reanalyses, fetal RHD was reported positive in 2,401 (58.3%), negative in 1,552 (37.7%), and inconclusive in 165 (4.0%) based on the first sample. After a second sample in 147 of 165, only 14 remained inconclusive, all resulting from a weak or silent maternal RHD gene. Using blood group serology of the newborns as the gold standard, the false-negative rate was 55 of 2,297 (2.4%) and the false-positive rate was 15 of 1,355 (1.1%). After exclusion of samples obtained before gestational week 8, the false-negative rate was 23 of 2,073 (1.1%) and the false positive rate was 14 of 1,218 (1.1%). Both sensitivity and specificity were close to 99% provided samples were not collected before gestational week 8. From gestational week 22, sensitivity was 100%. CONCLUSION: Fetal RHD detection in early pregnancy using a single-exon assay in a routine clinical setting is feasible and accurate. LEVEL OF EVIDENCE: I. PMID- 22776964 TI - Systems biology meets toxicology. PMID- 22776965 TI - Early increases in soluble amyloid-beta levels coincide with cholinergic degeneration in 3xTg-AD mice. AB - Accumulation of amyloid-beta peptides (Abeta) and cholinergic degeneration are hallmarks of Alzheimer's disease (AD). In a triple transgenic mouse model of AD (3xTg-AD), soluble Abeta42 levels were detected in the septum by 2 months of age, reaching their highest levels at 3-6 months and decreasing at 12 months. Deficits in the number of septal cholinergic neurons and the length of hippocampal cholinergic axons were observed starting at 4 months in 3xTg-AD mice. Our results show that septal Abeta and septohippocampal cholinergic pathology in 3xTg-AD mice occur at an early stage of disease. PMID- 22776966 TI - Focal adhesion kinase activates NF-kappaB via the ERK1/2 and p38MAPK Pathways in amyloid-beta25-35-induced apoptosis in PC12 cells. AB - Increasing evidence supports that amyloid plaques, comprised of amyloid-beta (Abeta), are a key feature of Alzheimer's disease (AD). But the mechanism of Abeta in AD is not yet fully understood. Previous studies have demonstrated that in Abeta-induced apoptosis of nerve cells, differentiated rat pheochromocytoma (PC12) cells, and microglia, nucleus factor kappa B (NF-kappaB) is activated. Meanwhile, focal adhesion kinase (FAK) is also activated. However, the relationship between NF-kappaB and FAK remains unclear. Using differentiated PC12 cells, we investigated this relationship in Abeta(25-35)-induced apoptosis. The results showed that FAK phosphorylation increased at 6-9 hours after Abeta treatment, slightly shorter than the activation of NF-kappaB (6-12 hours). In this process, both extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation levels were increased. After FAK expression was inhibited by its siRNA, the activities of ERK1/2, p38MAPK, and NF-kappaB were all suppressed. When ERK1/2 and p38MAPK expressions were inhibited by their siRNAs respectively, NF-kappaB activity was also suppressed. But FAK phosphorylation was not affected. When NF-kappaB expression was inhibited, all of the phosphorylation levels of FAK, ERK1/2, and p38MAPK were not affected. These phenomena indicated that FAK is upstream of ERK1/2, p38MAPK, and NF-kappaB, and meanwhile both of ERK1/2 and p38MAPK are upstream of NF kappaB. Co-immunoprecipitation results demonstrated that it is ERK1/2, but not p38MAPK, which directly interacts with IkappaB kinase. Taken together, our results suggest that FAK activates NF-kappaB via ERK1/2 and p38MAPK pathways in Abeta(25-35)-induced apoptosis of differentiated PC12 cells. PMID- 22776967 TI - Emotional decoding abilities in Alzheimer's disease: a meta-analysis. AB - Studies on emotional processing in Alzheimer's disease (AD) have reported abnormalities in emotional decoding. However, it remains unclear whether the impairment depends on a general cognitive decline that characterizes these patients or is an independent deficit. We conducted a comprehensive meta-analysis of existing studies that compared AD patients with age-matched healthy older adults (HOA) on measures of emotional decoding abilities. Our first goal was to quantify the magnitude of the AD patients' deficit. The second goal was to identify variables that may modulate the deficit, including emotional task design and participants' characteristics. The random-effects model analysis on 212 effect sizes indicated that AD patients showed significant impairment in emotional decoding abilities. This deficit is consistent regardless of the emotional task, stimuli, type of emotion considered, or disease severity. After we controlled for cognitive status, the emotional performance in AD patients was still poorer than that in HOA. The effect size of emotional performance was significantly lower when the cognitive status was considered than when it was not. Thus, our results suggest that impaired emotion processing in AD patients cannot be solely explained by the cognitive deficit. These findings provide evidence that progressive neuropathological changes characterizing the disease could affect emotional processing, which may suggest that clinicians should be sensitive to the emergence of impairments in emotional decoding. Further research that addresses the limitations of existing studies is needed to draw conclusions about methodological issues and the impact of the AD patient's depression symptoms on emotional decoding. PMID- 22776969 TI - Dendritic spine abnormalities in hippocampal CA1 pyramidal neurons underlying memory deficits in the SAMP8 mouse model of Alzheimer's disease. AB - SAMP8 is a strain of mice with accelerated senescence. These mice have recently been the focus of attention as they show several alterations that have also been described in Alzheimer's disease (AD) patients. The number of dendritic spines, spine plasticity, and morphology are basic to memory formation. In AD, the density of dendritic spines is severely decreased. We studied memory alterations using the object recognition test. We measured levels of synaptophysin as a marker of neurotransmission and used Golgi staining to quantify and characterize the number and morphology of dendritic spines in SAMP8 mice and in SAMR1 as control animals. While there were no memory differences at 3 months of age, the memory of both 6- and 9-month-old SAMP8 mice was impaired in comparison with age matched SAMR1 mice or young SAMP8 mice. In addition, synaptophysin levels were not altered in young SAMP8 animals, but SAMP8 aged 6 and 9 months had less synaptophysin than SAMR1 controls and also less than 3-month-old SAMP8 mice. Moreover, while spine density remained stable with age in SAMR1 mice, the number of spines started to decrease in SAMP8 animals at 6 months, only to get worse at 9 months. Our results show that from 6 months onwards SAMP8 mice show impaired memory. This age coincides with that at which the levels of synaptophysin and spine density decrease. Thus, we conclude that together with other studies that describe several alterations at similar ages, SAMP8 mice are a very suitable model for studying AD. PMID- 22776971 TI - HO-1/BVR-a system analysis in plasma from probable Alzheimer's disease and mild cognitive impairment subjects: a potential biochemical marker for the prediction of the disease. AB - Several studies showed increased oxidative and nitrosative stress in plasma from patients with Alzheimer's disease (AD), however, little and controversial knowledge has emerged about the antioxidant functionality of the heme oxygenase 1/biliverdin reductase-A (HO-1/BVR-A) system in blood. The current study reports increased levels of both HO-1 and BVR-A in plasma from probable AD patients, as a result of the increased oxidative environment. However, the increase of oxidative stress in plasma result also in the increase of BVR-A 3-nitrotyrosine levels and the decrease of BVR-A phosphotyrosine levels and reductase activity, suggesting that nitrosative stress play the prominent oxidative role in plasma during AD. Our data on HO-1/BVR-A status in plasma closely correlate with recent reports in hippocampus of subjects with AD and arguably its early form, mild cognitive impairment. Moreover, we show that alterations on HO-1/BVR-A system are tightly connected with cognitive decline indexed by Mini-Mental Status Exam scores. We hypothesize that the HO-1/BVR-A system status in plasma might reflect the ongoing situation in the brain, offering an important biochemical tool for the potential prediction of AD at the earliest stages of the disease. PMID- 22776970 TI - The effects of ramipril in individuals at risk for Alzheimer's disease: results of a pilot clinical trial. AB - Research shows that certain antihypertensives taken during midlife confer Alzheimer's disease (AD) related benefits in later life. We conducted a clinical trial to evaluate the extent to which the angiotensin converting enzyme inhibitor (ACE-I), ramipril, affects AD biomarkers including cerebrospinal fluid (CSF) amyloid-beta (Abeta) levels and ACE activity, arterial function, and cognition in participants with a parental history of AD. This four month randomized, double blind, placebo-controlled, pilot clinical trial evaluated the effects of ramipril, a blood-brain-barrier crossing ACE-I, in cognitively healthy individuals with mild, or Stage I hypertension. Fourteen participants were stratified by gender and apolipoprotein E epsilon4 (APOE epsilon4) status and randomized to receive 5 mg of ramipril or matching placebo daily. Participants were assessed at baseline and month 4 on measures of CSF Abeta(1-42) and ACE activity, arterial function, and cognition. Participants were middle-aged (mean 54 y) and highly educated (mean 15.4 y), and included 50% men and 50% APOE epsilon4 carriers. While results did not show a treatment effect on CSF Abeta(1 42) (p = 0.836), data revealed that ramipril can inhibit CSF ACE activity (p = 0.009) and improve blood pressure, however, there were no differences between groups in arterial function or cognition. In this study, ramipril therapy inhibited CSF ACE activity and improved blood pressure, but did not influence CSF Abeta1-42. While larger trials are needed to confirm our CSF Abeta results, it is possible that prior research reporting benefits of ACE-I during midlife may be attributed to alternative mechanisms including improvements in cerebral blood flow or the prevention of angiotensin II-mediated inhibition of acetylcholine. PMID- 22776972 TI - Improvement of glucose tolerance by rhein with restored early-phase insulin secretion in db/db mice. AB - AIMS: In the present study, we investigated whether rhein exerted hypoglycemic action and rhein's effect on the pancreatic beta cell in db/db mice. MATERIALS AND METHODS: Thirty 4-week-old db/db mice were randomized to treatment with rhein (120 mg/kg) (no.=15) and placebo (1% natrium cellulose solution) (no.=15) for 8 weeks, respectively. Fifteen age-matched non-diabetic littermates db/m mice treated with placebo were studied as non-diabetic control. After an 8-week treatment, ip glucose tolerance test (IPGTT) and arginine tolerance test were performed. Area under curve (AUC) of insulin levels in IPGTT was calculated to evaluate insulin secretory function. Immunohistochemical staining of insulin was performed to estimate beta cell mass. TUNEL assay was performed to determine beta cell apoptosis. Islet isolation and perifusion were performed to evaluate kinetics of insulin release in vitro, especially first-phase insulin. RESULTS: Compared with control group, AUC of glucose concentrations significantly decreased in the rhein-treated group (p<0.05). Simultaneously, AUC of insulin levels increased in the rhein-treated group (p<0.05), especially in the first 30 min after glucose load. Perifusion showed that the rhein-treated group manifested a significantly increase of first-phase insulin secretion. Immunohistochemical study and TUNEL assay showed that rhein treatment greatly preserved beta cell mass and inhibited beta cell apoptosis. CONCLUSIONS: Rhein treatment significantly improved glucose- dependent and independent insulin secretion by preservation of beta cell mass and inhibition of beta cell apoptosis in db/db mice. The characteristics of rhein may make it a novel therapeutic means for preventing from or curing diabetes in the near future. PMID- 22776973 TI - Pre-surgical treatment with somatostatin analogues in patients with acromegaly: the case for. PMID- 22776974 TI - Pre-surgical treatment with somatostatin analogues in patients with acromegaly: the case against. PMID- 22776975 TI - Endocrinology and art. Judith and Holofernes--Anonymous (XVII century). PMID- 22776976 TI - Benign neurological recovery with low recurrence and low peridural fibrosis rate in pediatric disc herniations after lumbar microdiscectomy. AB - Lumbar disc herniation (LDH) is a very rare clinical entity in the pediatric age group, therefore only a few clinical studies have until now investigated the clinical behavior of pediatric LDH. The natural clinical history, postoperative neurological recovery with radiological follow-up and quality of life related to the disorder continue to be unknown. We prospectively planned and designed two groups of LDH patients scheduled for surgery in this study. The operations were performed by the same surgeon in a randomized fashion. The first group consisted of pediatric patients and the second group of adult patients. Both groups contained 32 cases. Postoperative neurological recovery was assessed using the visual analog scale and Aberdeen Low Back Pain Scale. Postoperative peridural fibrosis was also evaluated in postcontrast magnetic resonance sections. After 3 years of follow-up, all parameters were significantly better in the pediatric LDH group with no recurrence of the disease. The pediatric LDH group was postoperatively better than the adult group both clinically and radiologically. Although LDH seems a catastrophic disease in the pediatric age group, the clinical picture and neurological recovery have a significantly more benign course than in adult patients even in operated cases. PMID- 22776978 TI - Malignant transformation in pediatric spinal intramedullary tumors: case-based update. AB - BACKGROUND: In children, intramedullary spinal cord neoplasms are rare. These are typically low-grade neuroepithelial tumors, most commonly astrocytomas, ependymomas, and gangliogliomas. Malignant transformation, while common in recurrent adult low-grade gliomas, is an unusual event in pediatric low-grade neoplasms, specifically in intramedullary spinal cord tumors. ILLUSTRATIVE CASES: We report two cases of malignant transformation in low-grade neuroepithelial tumors of the pediatric intramedullary spinal cord. Two children with intramedullary tumors, one with a WHO grade I ganglioglioma and one with a low grade astrocytoma, were treated surgically, diagnosed histologically, and followed through the course of their disease. Both patients' tumors transformed to higher grades without prior irradiation or chemotherapy, and without a genetic predisposition to tumorigenesis. DISCUSSION: Malignant transformation can occur in low-grade intramedullary neoplasms in children. This is a novel documented event for pediatric intramedullary spinal cord tumors and a rare event for all pediatric low-grade neuroepithelial tumors without induction by irradiation. A survey of the relevant literature reveals an underwhelming number of studies focusing on malignant transformation in children's CNS tumors relative to adults. Further investigation into molecular mechanisms of pediatric low-grade neoplasms may reveal more aggressive tumor sub-variants predisposed to malignant degeneration. PMID- 22776979 TI - Widely metastatic meningioma. PMID- 22776980 TI - Probiotics modulate host-microbe interaction in the placenta and fetal gut: a randomized, double-blind, placebo-controlled trial. AB - BACKGROUND: Early host-microbe interaction provides important maturational stimuli for the developing immune system. The role of prenatal microbial contact remains elusive. OBJECTIVES: Our aim was to investigate whether microbes in placenta or amniotic fluid affect fetal innate immune gene expression during late pregnancy and whether innate immune gene expression profiles in the placenta and the fetal gut may be modulated by dietary supplementation with specific probiotics. METHODS: Altogether 43 pregnant women were randomized to receive (1) Bifidobacterium lactis, (2) B. lactis in combination with Lactobacillus rhamnosus GG (LGG) or (3) placebo for 14 days before elective cesarian section at full term in a double-blind clinical trial. Bacteria in amniotic fluid and placenta were detected by quantitative (q)PCR. The expression of Toll-like receptor (TLR) related genes in the placenta and meconium samples was assessed by qPCR. Gene expression patterns in meconium were interpreted to reflect immune physiology in the fetal gut. RESULTS: The study was completed by 29 mother-infant pairs. Bacterial DNA was detected in all placenta samples. Microbial DNA in amniotic fluid and placenta was associated with changes in TLR-related gene expression in the fetal intestine. Maternal probiotic supplementation significantly modulated the expression of TLR-related genes both in the placenta and in the fetal gut. CONCLUSIONS: Microbial contact in utero is associated with changes in fetal intestinal innate immune gene expression profile. Fetal and placental immune physiology may be modulated by maternal dietary intervention using specific probiotics. PMID- 22776981 TI - A confidence set inference method for identifying SNPs that regulate quantitative phenotypes. AB - AIMS: We introduce a family-based confidence set inference (CSI) method that can be used in preliminary genome-wide association studies to obtain confidence sets of SNPs that contribute a specific percentage to the additive genetic variance of quantitative traits. METHODS: Developed in the framework of generalized linear mixed models, the method utilizes data from outbred families of arbitrary size and structure. Through our own simulation study and analysis of the Genetics Analysis Workshop 16 simulated data, we study the properties of our method and compare its performance to that of the family association method described by Chen and Abecasis [Am J Hum Genet 2007;81:913-926]. We also analyze the Framingham Heart Study data to identify SNPs regulating high-density lipoprotein levels. RESULTS: The simulation studies demonstrated that CSI yields confidence sets with correct coverage and that it can outperform the method introduced by Chen and Abecasis [Am J Hum Genet 2007;81:913-926]. Furthermore, we identified five SNPs that potentially regulate high-density lipoprotein levels: rs9989419, rs11586238, rs1754415, rs9355648, and rs9356560. CONCLUSION: The CSI method provides confidence sets of SNPs that contribute to the genetic variance of quantitative traits and is a competitive alternative to currently used family association methods. The approach is particularly useful in genome-wide association studies as it significantly reduces the number of SNPs investigated in follow-up studies. PMID- 22776983 TI - Tunable wrinkling pattern in annular graphene under circular shearing at inner edge. AB - This work is concerned with the wrinkling phenomenon observed in an annular graphene sheet under circular shearing at its inner edge. By performing molecular mechanics simulations on the aforementioned loaded annular graphene sheet, it is observed that the unusual wrinkles formed are confined to within an annulus that hugs the perimeter of the inner radius. This confined wrinkling pattern is in contrast to the wrinkling patterns that spread throughout rectangular graphene sheets under tension or shear. The present wrinkling pattern is characterized by a wave number and wrinkle profile. The wave number at the bifurcation wrinkle is found to depend only on the inner radius of the annular graphene and it increases almost linearly with increasing inner radius. The orientation of these developed waves is found to be at a constant angle and independent from the radii ratio of annular graphene. The wrinkle profile in terms of wave amplitude and wavelength depends on the magnitude of the circular shearing. The predictable formation of wrinkles in annular graphene can be exploited for applications in nano-force sensors, tunable magnetic or electronic devices, as well as patterned stretchable electronics. PMID- 22776984 TI - Coronary artery disease: the 6-min walk test is useful for assessing prognosis in stable, ambulatory patients. PMID- 22776985 TI - Atrial fibrillation: Is short-term antiarrhythmic therapy an option? PMID- 22776986 TI - Risk factors: Calcium supplements and cardiovascular risk. PMID- 22776988 TI - Antiplatelet therapy: Treatment with ticagrelor for 12 months after ACS is cost effective. PMID- 22776990 TI - Acoustofluidics 16: acoustics streaming near liquid-gas interfaces: drops and bubbles. AB - In this sixteenth part of the series on "Acoustofluidics-exploiting ultrasonic standing waves forces and acoustic streaming in microfluidic systems for cell and particle manipulation," we continue our discussion on the analytical aspects of the streaming phenomenon. In particular, the use of the singular perturbation technique for this class of problems is delineated with a set of examples where fluid-fluid interaction takes place. In this category, we focus on drops and bubbles, and deal specifically with the effect of interfacial mobility on the streaming flow. PMID- 22776987 TI - Secondary revascularization after CABG surgery. AB - CABG surgery is an effective way to improve symptoms and prognosis in patients with advanced coronary atherosclerotic disease. Despite multiple improvements in surgical technique and patient treatment, graft failure after CABG surgery occurs in a time-dependent fashion, particularly in the second decade after the intervention, in a substantial number of patients because of atherosclerotic progression and saphenous-vein graft (SVG) disease. Until 2010, repeat revascularization by either percutaneous coronary intervention (PCI) or surgical techniques was performed in these high-risk patients in the absence of specific recommendations in clinical practice guidelines, and within a culture of inadequate communication between cardiac surgeons and interventional cardiologists. Indeed, some of the specific technologies developed to reduce procedural risk, such as embolic protection devices for SVG interventions, are largely underused. Additionally, the implementation of secondary prevention, which reduces the need for reintervention in these patients, is still suboptimal. In this Review, graft failure after CABG surgery is examined as a clinical problem from the perspective of holistic patient management. Issues such as the substrate and epidemiology of graft failure, the choice of revascularization modality, the specific problems inherent in repeat CABG surgery and PCI, and the importance of secondary prevention are discussed. PMID- 22776989 TI - Bethesda criteria for microsatellite instability testing: impact on the detection of new cases of Lynch syndrome. AB - In 1997 Bethesda Guidelines (BG) were established and in 2004 those criteria were revised (RBG), with the main goal of selecting colorectal cancers (CRC) that should be subjected to microsatellite instability (MSI) testing. High microsatellite instability (MSI-H) is an intermediate marker for mutational analysis of the mismatch repair (MMR) genes involved in the genesis of Lynch Syndrome (LS). We aimed to evaluate and compare BG/RBG in the detection of MSI-H and subsequent identification of pathogenic MMR genes mutations. We included 174 patients with CRC and indication for MSI analysis according to BG or RBG. MSI testing was performed with the Bethesda markers and mutational analysis of MLH1, MSH2 and MSH6 genes undertaken with DGGE, MLPA and direct sequencing. One hundred fourteen of 174 patients (65.5 %) fulfilled BG and all of them RBG. With the BG, MSI-H was detected in 37/114 (32.5 %) CRCs and mutational analysis was positive in 14/37 (37.8 %) patients. The RBG led to detection of MSI-H in 49/174 (28.2 %) of the CRCs, having the mutational analysis been positive in 16/49 (32.7 %) patients. We could identify 14/114 (12.3 %) new cases of LS, through BG and 16/174 (9.2 %) via RBG. BG presented a similar overall percentage for the detection of MSI-H and mutations when compared with RBG. RBG implicated the analysis of more patients, though they gave rise to detection of two additional LS cases. This difference has a significant impact on the establishment of preventive measures, mainly for CRC, in all the mutation-carriers belonging to these families. PMID- 22776991 TI - Association between evidence-based standardized protocols in emergency departments with childhood asthma outcomes: a Canadian population-based study. AB - OBJECTIVE: To determine whether children treated in emergency departments (EDs) with evidence-based standardized protocols (EBSPs) containing evidence-based content and format had lower risk of hospital admission or ED return visit and greater follow-up than children treated in EDs with no standardized protocols in Ontario, Canada. DESIGN: Retrospective population-based cohort study of children with asthma. We used multivariable logistic regression to estimate risk of outcomes. SETTING: All EDs in Ontario (N = 146) treating childhood asthma from April 2006 to March 2009. PARTICIPANTS: Thirty-one thousand one hundred thirty eight children (aged 2 to 17 years) with asthma. MAIN EXPOSURE Type of standardized protocol (EBSPs, other standardized protocols, or none). MAIN OUTCOME MEASURES: Hospital admission, high-acuity 7-day return visit to the ED, and 7-day outpatient follow-up visit. RESULTS The final cohort made 46 510 ED visits in 146 EDs. From the index ED visit, 4211 (9.1%) were admitted to the hospital. Of those discharged, 1778 (4.2%) and 7350 (17.4%) had ED return visits and outpatient follow-up visits, respectively. The EBSPs were not associated with hospitalizations, return visits, or follow-up (adjusted odds ratio, 1.17 [95% CI, 0.91-1.49]; adjusted odds ratio, 1.10 [95% CI, 0.86-1.41]; and adjusted odds ratio, 1.08 [95% CI, 0.87-1.35], respectively). CONCLUSIONS: The EBSPs were not associated with improvements in rates of hospital admissions, return visits to the ED, or follow-up. Our findings suggest the need to address gaps linking improved processes of asthma care with outcomes. PMID- 22776992 TI - Engineering a homobutanol fermentation pathway in Escherichia coli EG03. AB - A homobutanol fermentation pathway was engineered in a derivative of Escherichia coli B (glucose [glycolysis] => 2 pyruvate + 2 NADH; pyruvate [pyruvate dehydrogenase] => acetyl-CoA + NADH; 2 acetyl-CoA [butanol pathway enzymes] + 4 NADH => butanol; summary stoichiometry: glucose => butanol). Initially, the native fermentation pathways were eliminated from E. coli B by deleting the genes encoding for lactate dehydrogenase (ldhA), acetate kinase (ackA), fumarate reductase (frdABCD), pyruvate formate lyase (pflB), and alcohol dehydrogenase (adhE), and the pyruvate dehydrogenase complex (aceEF-lpd) was anaerobically expressed through promoter replacement. The resulting strain, E. coli EG03 (DeltafrdABCD DeltaldhA DeltaackA DeltapflB Delta adhE DeltapdhR ::pflBp6-aceEF lpd DeltamgsA), could generate 4 NADH for every glucose oxidized to two acetyl CoA through glycolysis and the pyruvate dehydrogenase complex. However, EG03 lost its ability for anaerobic growth due to the lack of NADH oxidation pathways. When the butanol pathway genes that encode for acetyl-CoA acetyltransferase (thiL), 3 hydroxybutyryl-CoA dehydrogenase (hbd), crotonase (crt), butyryl-CoA dehydrogenase (bcd, etfA, etfB), and butyraldehyde dehydrogenase (adheII) were cloned from Clostridium acetobutylicum ATCC 824, and expressed in E. coli EG03, a balanced NADH oxidation pathway was established for homobutanol fermentation (glucose => 4 NADH + 2 acetyl-CoA => butanol). This strain was able to convert glucose to butanol (1,254 mg l(-1)) under anaerobic condition. PMID- 22776993 TI - Redefining XynA from Penicillium funiculosum IMI 378536 as a GH7 cellobiohydrolase. AB - The secretome of Penicillium funiculosum contains two family GH7 enzymes, one of which (designated XynA) has been described as a xylanase. This is unusual because it is the only xylanase in family GH7, which is mainly composed of cellobiohydrolases and endoglucanases, and also because XynA is highly similar to the cellobiohydrolase I from Talaromyces emersonii and Trichoderma reesei (72 and 65 % identity, respectively). To probe this enigma, we investigated the biochemical properties of XynA, notably its activity on xylans and beta-D glucans. A highly pure sample of XynA was obtained and used to perform hydrolysis tests on polysaccharides. These revealed that XynA is 100-fold more active on beta-1,4-glucan than on xylan. Likewise, XynA was active on both 4-nitrophenyl beta-D-lactopyranoside (pNP-beta-D-Lac) and 4-nitrophenyl-beta-D-cellobioside (pNP-cellobiose), which shows that XynA is principally an exo-acting type 1 cellobiohydrolase enzyme that displays 5.2-fold higher performance on pNP cellobiose than on pNP-beta-D-Lac. Finally, analyses performed using cellodextrins as substrate revealed that XynA mainly produced cellobiose (C2) from substrates containing three or more glucosyl subunits, and that C2 inhibits XynA at high concentrations (IC(50) (C2) = 17.7 MUM). Overall, this study revealed that XynA displays typical cellobiohydrolase 1 activity and confirms that the description of this enzyme in public databases should be definitively amended. Moreover, the data provided here complete the information provided by a previous proteomics investigation and reveal that P. funiculosum secretes a complete set of cellulose-degrading enzymes. PMID- 22776994 TI - Immediate use of an arteriovenous prosthetic graft for life-saving dialysis in a child. AB - BACKGROUND: Autologous arteriovenous fistulas (AVFs) are the current gold standard for vascular access in hemodialysis (HD). However, in pediatric patients, specific clinical settings may contraindicate the procedure, thus mandating the use of a prosthetic graft (PG). CASE-DIAGNOSIS/TREATMENT: We report a case of successful polycarbonate urethane graft implantation and subsequent resumption of HD 12 h after the procedure in a young girl with end-stage renal disease (ESRD), challenging vascular anatomy and the absence of vascular access. CONCLUSIONS: The use of polycarbonate urethane PGs in children with ESRD and difficult vascular accesses may represent a valid alternative for early resumption of HD. PMID- 22776995 TI - A polymorphism in the gene of the endocannabinoid-degrading enzyme FAAH (FAAH C385A) is associated with emotional-motivational reactivity. AB - RATIONALE: The endocannabinoid (eCB) system is implicated in several psychiatric disorders. Investigating emotional-motivational dysfunctions as underlying mechanisms, a study in humans revealed that in the C385A polymorphism of the fatty acid amide hydrolase (FAAH), the degrading enzyme of the eCB anandamide (AEA), A carriers, who are characterized by increased signaling of AEA as compared to C/C carriers, exhibited reduced brain reactivity towards unpleasant faces and enhanced reactivity towards reward. However, the association of eCB system with emotional-motivational reactivity is complex and bidirectional due to upcoming compensatory processes. OBJECTIVES: Therefore, we further investigated the relationship of the FAAH polymorphism and emotional-motivational reactivity in humans. METHODS: We assessed the affect-modulated startle, and ratings of valence and arousal in response to higher arousing pleasant, neutral, and unpleasant pictures in 67 FAAH C385A C/C carriers and 45 A carriers. RESULTS: Contrarily to the previous functional MRI study, A carriers compared to C/C carriers exhibited an increased startle potentiation and therefore emotional responsiveness towards unpleasant picture stimuli and reduced startle inhibition indicating reduced emotional reactivity in response to pleasant pictures, while both groups did not differ in ratings of arousal and valence. CONCLUSIONS: Our findings emphasize the bidirectionality and thorough examination of the eCB system's impact on emotional reactivity as a central endophenotype underlying various psychiatric disorders. PMID- 22776996 TI - In vitro antioxidant and antiproliferative potential of medicinal plants used in traditional Indian medicine to treat cancer. AB - OBJECTIVE: The goal of this study was to evaluate the antioxidant and antiproliferative activities of 10 traditional medicinal plants, Asclepias curassavica, Ophiorrhiza mungos Linn., Cynodon dactylon (L.) Pers, Costus speciosus (J. Koenig.) Smith Costaceae, Achyranthes aspera L., Amaranthus tristis Roxb., Blepharis maderaspatensis L., Merremia emerginata Hall.f., Aegle marmelos Corr., and Tabernaemontana heyneana Wall., used in the traditional Indian system of medicine as a cure for cancer. The present study focuses on the anticancer potential of traditional medicinal plants to induce apoptosis in cancer cell lines. METHODS: Plants were sequentially extracted with hexane, ethyl acetate, and methanol. The extract was concentrated to yield the crude extract, which was tested for antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl, nitric oxide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays on four cancer cell lines and a normal cell line. The anticancer potential of cytotoxic extracts was determined by the Annexin-fluorescein isothiocyanate-conjugated assay in human colon adenocarcinoma cell lines (COLO 320 DM). RESULTS: All the tested extracts showed significant antioxidant and antiproliferative activities in a concentration- and time-dependant manner in the following descending order: A. curassavica > C. dactylon > C. speciosus root > A. tristis > M. emarginata > O. mungos > T. Heyneana > B. maderaspatensis > A. marmelos > A. aspera. CONCLUSION: The results of the present study support the need of further studies to isolate potential anticancer drug with cancer cell-specific cytotoxicity. Additionally, the study supports the anticancer property of medicinal plants used in the traditional Indian medicine system and further evaluation of the selected medicinal plants for an effective anticancer drug with minimal side effects. PMID- 22776997 TI - Thermally induced [3+2] cyclization of aniline-tethered alkylidenecyclopropanes: a facile synthetic protocol of pyrrolo[1,2-a]indoles. AB - A facile synthetic method of functionalized pyrrolo[1,2-a]indoles has been developed via a thermally-induced ring-opening and cyclization reaction from aniline-tethered alkylidenecyclopropanes with aldehydes. PMID- 22776998 TI - High-grade glioma motility reduced by genetic knockdown of KCC3. AB - Cell motility is dependent on a coordinated reorganization of the cytoskeleton, membrane recycling, and focal adhesion to the extracellular matrix. Each of these cellular processes involves re-distribution of cell water, which is facilitated by the transport of inorganic ions (with obligatory water movement). Scratch wound healing assays of Wistar C6 glioblastoma cells demonstrated cell motility in advance of cell proliferation. Although bumetanide inhibition of Na-K-2Cl cotransport activity did not affect cell motility, treatment of glioma cells with furosemide to inhibit K-Cl cotransport activity prevented ~75% of wound closure in a reversible reaction. Genetic silencing of KCC3 with short hairpin interfering RNA reduced protein expression by 40 - 60%, K(+) influx by ~50%, and cell motility by ~50%. Appearance of KCC1 mRNA and KCC3 mRNA at 25 PCR cycles versus KCC4 mRNA at 35 PCR cycles, suggests more KCC1/KCC3 expression in both primary rat astrocytes and C6 glioma cells. Altogether, these experiments suggest that the presence/function of multiple isoforms of the Na(+-)independent K-Cl cotransporter may have a role in glioma cell motility. PMID- 22776999 TI - Perioperative factors associated with prolonged intensive care unit and hospital length of stay after pediatric neurosurgery. AB - OBJECTIVES: This study aims to describe the association between different postoperative complications and the length of hospital stay among children undergoing neurosurgical procedures. METHODS: A retrospective cohort study was carried out between May 2004 and May 2009 in a tertiary community hospital. All postoperative complications following neurosurgical procedures and their association with the main outcomes [length of intensive care unit (ICU) and hospital stay] were investigated in a univariate and multivariate analysis. RESULTS: The medical records of 198 patients treated during the study period were reviewed. The most frequently performed surgeries were ventriculoperitoneal shunting (16.7%), correction of craniosynostosis (30%) and brain tumor resections (28.3%). Of the 198 patients eligible for this analysis, 79 (39.9%) suffered from at least one complication. The most frequent complications were fever (30.3%), hypothermia (16%), postextubation laryngitis (15.1%) and postoperative bleeding (7%). Factors independently associated with a longer pediatric ICU stay were fever (odds ratio 1.39, 95% confidence interval 1.1-3.2; p = 0.001), laryngitis (odds ratio 2.24, 95% confidence interval 1.8-5.2; p = 0.001), postoperative bleeding requiring reoperation (odds ratio 1.8, 95% confidence interval 1.4-3.9; p < 0.001) and infection (odds ratio 3.71, 95% confidence interval 1.8-12.4; p = 0.033). Fever (odds ratio 2.54, 95% confidence interval 2-7.4; p = 0.001) and infection (odds ratio 11.23, 95% confidence interval 4-22.4; p = 0.003) were related to the total length of the patient's hospital stay. CONCLUSIONS: In this study population, most elective neurosurgical procedures were not associated with significant complications, and morbidity and mortality were low. Some complications significantly influenced patients' outcomes and should be monitored for early diagnosis. This study may improve our understanding and identification of postoperative outcomes in pediatric neurosurgery. PMID- 22777000 TI - Synergistical toll-like receptors activated dendritic cells induce antitumor effects against carcinoembryonic antigen-expressing colon cancer. AB - PURPOSE: Dendritic cell (DC)-based cancer vaccine represents a promising immunotherapy against cancer. There has been recent evidence which have suggested that toll-like receptor (TLR) ligands may be critical for DC preparation; this was usually omitted in the past. Our study is designed to investigate if the vaccination of synergistical toll-like receptors activated DCs can induce more potent cytotoxic T Lymphocytes (CTL) responses and antitumor activity in carcinoembryonic antigen (CEA) transgenic mouse tumor models. METHODS: We involved combination of TLR3 and TLR7/8 ligands in culture protocol of DCs. The DCs' surface molecules expression, IL-12 secretion and proliferation capacity of lymphocytes were tested. We also investigate the CTL activity against MC38-CEA colon tumor cells and the prophylactic and therapeutic effects of DC vaccination in subcutaneous mouse colon tumor models. RESULTS: Compared with conventionally generated DCs, we showed synergistic TLR-activated DCs exhibited higher surface molecule expression, significantly higher secretion of IL-12 and more potent proliferating capacity of lymphocytes. Synergistic TLR-activated DCs were also able to induce lymphocytes possessing the specific cytotoxicity against MC38-CEA cells in vitro. Vaccination with CEA epitope pulsed TLR-activated DCs elicited antigen-specific preventive effect on MC38-CEA tumors, but failed to cure the tumor-bearing mice, that may be due to the suboptimal epitope selected and host immunosuppression. CONCLUSIONS: Our results have proved that combined activation of TLRs can lead to better maturation status of DCs and also induce more effective antitumor immune responses against colon cancer, suggesting this may be a potential strategy to develop more powerful DC cancer vaccines. PMID- 22777002 TI - Ultrafast charge-transfer dynamics of donor-substituted truxenones. AB - The photophysics of two donor-substituted truxenone derivatives has been studied by femtosecond time-resolved transient absorption spectroscopy. The systems consist of a central truxenone acceptor with three triarylamine (TARA) branches which act as electron donors. Upon excitation in the visible regime an electron is transferred from the donor to the acceptor, generating a charge-separated state. This state can be probed via the characteristic absorption of the TARA radical cation around 700 nm. A second absorption band around 420 nm exhibits the same kinetics and is assigned to an absorption of the radical anion of the truxenone moiety. The back electron transfer and the recovery of the ground state can be interpreted within the framework of Marcus theory. To study the dependence of the back electron transfer on the electronic coupling, the distance between the donor and the acceptor was adjusted. Two solvents were employed, dimethylsulfoxide and dichloroethane. A biexponential decay of the bands assigned to the charge-separated state was observed, with time constants in the picosecond range. Surprisingly, the rates for electron back transfer do not follow the simple picture of the donor-acceptor distance being the determining factor. The observations are explained within a model that additionally takes steric interactions between the donor and the acceptor into account. PMID- 22777001 TI - Possibility of ex vivo animal training model for colorectal endoscopic submucosal dissection. AB - PURPOSE: Colorectal endoscopic submucosal dissection (ESD) has not been standardized due to technical difficulties and requires extensive training for reliability. Ex vivo animal model is convenient, but has no blood flow. The objective of this study is to evaluate the characteristics of various ex vivo animal models including a blood flow model for colorectal ESD training and the usefulness of practicing endoscopic hemostasis and closure using an animal model. METHODS: Harvested porcine cecum, rectum, and stomach and bovine cecum and rectum were analyzed regarding ease of mucosal injection, degree of submucosal elevation, and status of the proper muscle layer. Ex vivo animal model with blood flow was made using the bovine cecum. The vessel around the cecum was detached, and red ink was injected. Endoscopic hemostasis for perioperative hemorrhage and endoscopic closure for perforation were performed in this model. RESULTS: Mucosal injection was easily performed in the bovine cecum and rectum. Submucosal elevation was low in the bovine cecum, while the proper muscle layer was not tight in the porcine rectum and bovine cecum. Endoscopic hemostasis were accomplished in six (60 %) out of ten procedures of the ex vivo blood flow model. In two non-experts, the completion rates of endoscopic closure were 40 and 60 % in the first five procedures. These rates became 100 % in the last five procedures. CONCLUSIONS: We have evaluated the characteristics of various ex vivo animal models and shown the possibility of training for endoscopic hemostasis and endoscopic closure in the ex vivo animal model. PMID- 22777003 TI - Brain growth of the domestic pig (Sus scrofa) from 2 to 24 weeks of age: a longitudinal MRI study. AB - An animal model with brain growth similar to humans, that can be used in MRI studies to investigate brain development, would be valuable. Our laboratory has developed and validated MRI methods for regional brain volume quantification in the neonatal piglet. The aim of this study was to utilize the MRI-based volume quantification technique in a longitudinal study to determine brain growth in domestic pigs from 2 to 24 weeks of age. MRI data were acquired from pigs 2-24 weeks of age using a 3-dimensional magnetization-prepared gradient echo sequence on a Magnetom Trio 3-tesla imager. Manual segmentation was performed for volume estimates of total brain, cortical, diencephalon, brainstem, cerebellar and hippocampal regions. Logistic modeling procedures were used to characterize brain growth. Total brain volume increased 130% (+/-12%) and 121% (+/-7%) from 2 to 24 weeks in males and females, respectively. The maximum increase in total brain volume occurred about the age of 4 weeks and 95% of whole brain growth occurred by the age of 21-23 weeks. Logistical modeling suggests there are sexually dimorphic effects on brain growth. For example, in females, the cortex was smaller (p = 0.04). Furthermore, the maximum growth of the hippocampus occurred about 5 weeks earlier in females than males, and the window for hippocampal growth was significantly shorter in females than males (p = 0.02, p = 0.002 respectively). These sexual dimorphisms are similar to what is seen in humans. In addition to providing important data on brain growth for pigs, this study shows pigs can be used to obtain longitudinal MRI data. The large increase in brain volume in the postnatal period is similar to that of human neonates and suggests pigs can be used to investigate brain development. PMID- 22777004 TI - Mitofusin 2-containing mitochondrial-reticular microdomains direct rapid cardiomyocyte bioenergetic responses via interorganelle Ca(2+) crosstalk. AB - RATIONALE: Mitochondrial Ca(2+) uptake is essential for the bioenergetic feedback response through stimulation of Krebs cycle dehydrogenases. Close association of mitochondria to the sarcoplasmic reticulum (SR) may explain efficient mitochondrial Ca(2+) uptake despite low Ca(2+) affinity of the mitochondrial Ca(2+) uniporter. However, the existence of such mitochondrial Ca(2+) microdomains and their functional role are presently unresolved. Mitofusin (Mfn) 1 and 2 mediate mitochondrial outer membrane fusion, whereas Mfn2 but not Mfn1 tethers endoplasmic reticulum to mitochondria in noncardiac cells. OBJECTIVE: To elucidate roles for Mfn1 and 2 in SR-mitochondrial tethering, Ca(2+) signaling, and bioenergetic regulation in cardiac myocytes. METHODS AND RESULTS: Fruit fly heart tubes deficient of the Drosophila Mfn ortholog MARF had increased contraction-associated and caffeine-sensitive Ca(2+) release, suggesting a role for Mfn in SR Ca(2+) handling. Whereas cardiac-specific Mfn1 ablation had no effects on murine heart function or Ca(2+) cycling, Mfn2 deficiency decreased cardiomyocyte SR-mitochondrial contact length by 30% and reduced the content of SR-associated proteins in mitochondria-associated membranes. This was associated with decreased mitochondrial Ca(2+) uptake (despite unchanged mitochondrial membrane potential) but increased steady-state and caffeine-induced SR Ca(2+) release. Accordingly, Ca(2+)-induced stimulation of Krebs cycle dehydrogenases during beta-adrenergic stimulation was hampered in Mfn2-KO but not Mfn1-KO myocytes, evidenced by oxidation of the redox states of NAD(P)H/NAD(P)(+) and FADH(2)/FAD. CONCLUSIONS: Physical tethering of SR and mitochondria via Mfn2 is essential for normal interorganelle Ca(2+) signaling in the myocardium, consistent with a requirement for SR-mitochondrial Ca(2+) signaling through microdomains in the cardiomyocyte bioenergetic feedback response to physiological stress. PMID- 22777005 TI - S-Nitrosation of beta-catenin and p120 catenin: a novel regulatory mechanism in endothelial hyperpermeability. AB - RATIONALE: Endothelial adherens junction proteins constitute an important element in the control of microvascular permeability. Platelet-activating factor (PAF) increases permeability to macromolecules via translocation of endothelial nitric oxide synthase (eNOS) to cytosol and stimulation of eNOS-derived nitric oxide signaling cascade. The mechanisms by which nitric oxide signaling regulates permeability at adherens junctions are still incompletely understood. OBJECTIVE: We explored the hypothesis that PAF stimulates hyperpermeability via S nitrosation (SNO) of adherens junction proteins. METHODS AND RESULTS: We measured PAF-stimulated SNO of beta-catenin and p120-catenin (p120) in 3 cell lines: ECV eNOSGFP, EAhy926 (derived from human umbilical vein), and postcapillary venular endothelial cells (derived from bovine heart endothelium) and in the mouse cremaster muscle in vivo. SNO correlated with diminished abundance of beta catenin and p120 at the adherens junction and with hyperpermeability. Tumor necrosis factor-alpha increased nitric oxide production and caused similar increase in SNO as PAF. To ascertain the importance of eNOS subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced SNO of beta catenin and p120 and significantly diminished association between these proteins in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Inhibitors of nitric oxide production and of SNO blocked PAF induced SNO and hyperpermeability, whereas inhibition of the cGMP pathway had no effect. Mass spectrometry analysis of purified p120 identified cysteine 579 as the main S-nitrosated residue in the region that putatively interacts with vascular endothelial-cadherin. CONCLUSIONS: Our results demonstrate that agonist induced SNO contributes to junctional membrane protein changes that enhance endothelial permeability. PMID- 22777007 TI - The field of microcirculation and vascular biology. PMID- 22777006 TI - LRP1-dependent endocytic mechanism governs the signaling output of the bmp system in endothelial cells and in angiogenesis. AB - RATIONALE: Among the extracellular modulators of Bmp (bone morphogenetic protein) signaling, Bmper (Bmp endothelial cell precursor-derived regulator) both enhances and inhibits Bmp signaling. Recently we found that Bmper modulates Bmp4 activity via a concentration-dependent, endocytic trap-and-sink mechanism. OBJECTIVE: To investigate the molecular mechanisms required for endocytosis of the Bmper/Bmp4 and signaling complex and determine the mechanism of Bmper's differential effects on Bmp4 signaling. METHODS AND RESULTS: Using an array of biochemical and cell biology techniques, we report that LRP1 (LDL receptor-related protein 1), a member of the LDL receptor family, acts as an endocytic receptor for Bmper and a coreceptor of Bmp4 to mediate the endocytosis of the Bmper/Bmp4 signaling complex. Furthermore, we demonstrate that LRP1-dependent Bmper/Bmp4 endocytosis is essential for Bmp4 signaling, as evidenced by the phenotype of lrp1-deficient zebrafish, which have abnormal cardiovascular development and decreased Smad1/5/8 activity in key vasculogenic structures. CONCLUSIONS: Together, these data reveal a novel role for LRP1 in the regulation of Bmp4 signaling by regulating receptor complex endocytosis. In addition, these data introduce LRP1 as a critical regulator of vascular development. These observations demonstrate Bmper's ability to fine-tune Bmp4 signaling at the single-cell level, unlike the spatial regulatory mechanisms applied by other Bmp modulators. PMID- 22777008 TI - Dying for the weekend: a retrospective cohort study on the association between day of hospital presentation and the quality and safety of stroke care. AB - OBJECTIVE: To examine the association between day of admission and measures of the quality and safety of the care received by patients with stroke. DESIGN: Retrospective cohort study of patients admitted to hospitals with stroke (codes I60-I64 from the International Statistical Classification of Diseases and Related Health Problems, Tenth Version) from April 1, 2009, through March 31, 2010. SETTING: English National Health Service public hospitals. PATIENTS: PATIENTS during the study period accounted for 93 621 admissions. We used logistic regression to adjust the outcome measures for case mix. MAIN OUTCOME MEASURES: Quality and safety measurements using 6 indicators spanning the hospital care pathway, from timely brain scans to emergency readmissions after discharge. RESULTS: Performance across 5 of the 6 measures was significantly lower on weekends (confidence level, 99%). One of the largest disparities was seen in rates of same-day brain scans, which were 43.1% on weekends compared with 47.6% on weekdays (unadjusted odds ratio, 0.83 [95% CI, 0.81-0.86]). In particular, the rate of 7-day in-hospital mortality for Sunday admissions was 11.0% (adjusted odds ratio, 1.26 [95% CI, 1.16-1.37], with Monday used as a reference) compared with a mean of 8.9% for weekday admissions. CONCLUSIONS: Strong evidence suggests that, nationally, stroke patients admitted on weekends are less likely to receive urgent treatments and have worse outcomes across a range of indicators. Although we adjusted the results for case mix, we cannot rule out some of the effect being due to unmeasured differences in patients admitted on weekends compared with weekdays. The findings suggest that approximately 350 in-hospital deaths each year within 7 days are potentially avoidable, and an additional 650 people could be discharged to their usual place of residence within 56 days if the performance seen on weekdays was replicated on weekends. PMID- 22777009 TI - Ultrasound confirmation of endotracheal tube position in neonates. AB - BACKGROUND: The placement of the endotracheal tube (ETT) in neonates is a challenging procedure that currently requires timely confirmation of tip placement by radiographic imaging. OBJECTIVE: We sought to determine if bedside ultrasound (US) could demonstrate ETT tip location in preterm and term newborns and offer a quick alternative method of ETT positioning. METHODS: We conducted a prospective pilot study of 30 newborns admitted to the UC San Diego Medical Center who had their ETT placement confirmed by chest radiographs. After a radiograph, each infant had a US exam with a 13-MHz linear transducer on a portable US machine. To assist localization, gentle longitudinal movement of the ETT of less than 0.5 cm was performed. Measurements from the tip of the ETT tip to the carina were made on chest radiograph and midsagittal US images. RESULTS: Study infants had a mean gestational age of 30.2 +/- 4.9 (SD) weeks and mean birth weight of 1,595.2 +/- 862 g. US images were taken a mean 2.9 +/- 2.2 h after radiographs. Data from 2 infants were excluded for poor radiograph image quality and extreme outlier values. The ETT was visualized by US in all newborns examined. We observed a good correlation between ETT tip-to-carina distance on US and radiograph (r(2) = 0.68) with minimal bias. Each study took less than 5 min to obtain without any clinical deterioration. CONCLUSIONS: Bedside US can visualize the anatomic position of the ETT position in preterm and term infants but further validation is required before routine clinical implementation. PMID- 22777010 TI - Interfacial growth behavior of SnO2 nanorods on {11 20} and {10 10} facets of alpha-Fe2O3. AB - SnO(2) nanorods with specific growth directions, [101] or [001], were fabricated on alpha-Fe(2)O(3) substrates via a simple hydrothermal method. The growth behavior of SnO(2) nanorods is facet-selective. Both {11 20} and {10 10} facets of alpha-Fe(2)O(3) are favorable to direct the growth of SnO(2) nanorods. The correlation between the crystallographic orientation of SnO(2) and the facets of alpha-Fe(2)O(3) is characterized by TEM observations and investigated on the basis of the interfacial lattice compatibility. Furthermore, the distribution and coordination of oxygen atoms at the interface of alpha-Fe(2)O(3)-SnO(2) heterostructure are analyzed, which reveals that only slight deviations from their original equilibrium positions are allowed for the formation of heterogeneous interface. And this lower energy activated interfacial construction is beneficial to the feasibility and stability of heterostructures. PMID- 22777011 TI - The proteoglycan repertoire of lymphoid cells. AB - Proteoglycans have been studied to a limited extent in lymphoid cells. In this study we have investigated the expression of proteoglycans in B-cells, CD4+ T cells, CD8+ T-cells, natural killer cells, as well as in nine different cell lines established from patients with lymphoid malignancies. Serglycin was the major proteoglycan expressed at mRNA level by the primary lymphocytes. None of the syndecans or glycpicans was detected at mRNA level in the primary lymphocytes, except for syndecan-4 in CD4+ T-cells and CD8+ T-cells. All lymphoid cell lines expressed serglycin mRNA, as well as one or several members of the syndecan and glypican families. Further, increased synthesis of proteoglycans was found in the cell lines compared to the primary lymphocytes, as well as the presence of heparan sulfate on the cell surface of five of the cells lines. Western blot analysis showed a close correlation between serglycin mRNA level and expression of serglycin core protein. Our results show that serglycin is a major proteoglycan in all the normal lymphoid cells and that these cells carry little, or none, proteoglycans on the cell surface. Serglycin was also a major proteoglycan in the malignant lymphoid cells, but these also expressed one or more types of cell surface proteoglycans. Thus, malignant transformation of lymphoid cells may be followed by increased synthesis of proteoglycans and expression of cell surface proteoglycans. PMID- 22777012 TI - Microfluidically-unified cell culture, sample preparation, imaging and flow cytometry for measurement of cell signaling pathways with single cell resolution. AB - We have developed a microfluidic platform that enables, in one experiment, monitoring of signaling events spanning multiple time-scales and cellular locations through seamless integration of cell culture, stimulation and preparation with downstream analysis. A combination of two single-cell resolution techniques-on-chip multi-color flow cytometry and fluorescence imaging provides multiplexed and orthogonal data on cellular events. Automated, microfluidic operation allows quantitatively- and temporally-precise dosing leading to fine time-resolution and improved reproducibility of measurements. The platform was used to profile the toll-like receptor (TLR4) pathway in macrophages challenged with lipopolysaccharide (LPS)-beginning with TLR4 receptor activation by LPS, through intracellular MAPK signaling, RelA/p65 translocation in real time, to TNF alpha cytokine production, all in one small macrophage population (< 5000 cells) while using minute reagent volume (540 nL/condition). The platform is easily adaptable to many cell types including primary cells and provides a generic platform for profiling signaling pathways. PMID- 22777013 TI - Sexual and social competition: broadening perspectives by defining female roles. AB - Males figured more prominently than females in Darwin's view of sexual selection. He considered female choice of secondary importance to male-male competition as a mechanism to explain the evolution of male ornaments and armaments. Fisher later demonstrated the importance of female choice in driving male trait evolution, but his ideas were largely ignored for decades. As sexual selection came to embrace the notions of parent-offspring and sexual conflict, and experimental tests of female choice showed promise, females began to feature more prominently in the framework of sexual selection theory. Recent debate over this theory has centred around the role of females, not only over the question of choice, but also over female-female competition. Whereas some have called for expanding the sexual selection framework to encompass all forms of female-female competition, others have called for subsuming sexual selection within a broader framework of social selection, or replacing it altogether. Still others have argued for linking sexual selection more clearly to other evolutionary theories such as kin selection. Rather than simply debating terminology, we must take a broader view of the general processes that lead to trait evolution in both sexes by clearly defining the roles that females play in the process, and by focusing on intra- and inter-sexual interactions in males and females. PMID- 22777014 TI - Aesthetic evolution by mate choice: Darwin's really dangerous idea. AB - Darwin proposed an explicitly aesthetic theory of sexual selection in which he described mate preferences as a 'taste for the beautiful', an 'aesthetic capacity', etc. These statements were not merely colourful Victorian mannerisms, but explicit expressions of Darwin's hypothesis that mate preferences can evolve for arbitrarily attractive traits that do not provide any additional benefits to mate choice. In his critique of Darwin, A. R. Wallace proposed an entirely modern mechanism of mate preference evolution through the correlation of display traits with male vigour or viability, but he called this mechanism natural selection. Wallace's honest advertisement proposal was stridently anti-Darwinian and anti aesthetic. Most modern sexual selection research relies on essentially the same Neo-Wallacean theory renamed as sexual selection. I define the process of aesthetic evolution as the evolution of a communication signal through sensory/cognitive evaluation, which is most elaborated through coevolution of the signal and its evaluation. Sensory evaluation includes the possibility that display traits do not encode information that is being assessed, but are merely preferred. A genuinely Darwinian, aesthetic theory of sexual selection requires the incorporation of the Lande-Kirkpatrick null model into sexual selection research, but also encompasses the possibility of sensory bias, good genes and direct benefits mechanisms. PMID- 22777015 TI - Sexual selection is a form of social selection. AB - Social selection influences the evolution of weapons, ornaments and behaviour in both males and females. Thus, social interactions in both sexual and non-sexual contexts can have a powerful influence on the evolution of traits that would otherwise appear to be detrimental to survival. Although clearly outlined by West Eberhard in the early 1980s, the idea that social selection is a comprehensive framework for the study of ornaments and weapons has largely been ignored. In West-Eberhard's view, sexual selection is a form of social selection-a concept supported by several lines of evidence. Darwin's distinction between natural and sexual selection has been useful, but recent confusion about the limits of sexual selection suggests that some traits are not easily categorized as naturally or sexually selected. Because social selection theory has much to offer the current debates about both sexual selection and reproductive competition in females, it is sometimes viewed, narrowly, to be most useful when considering female roles. However, social selection theory encompasses much more than female reproductive competition. Our goal here was to provide that broader perspective. PMID- 22777017 TI - The social selection alternative to sexual selection. AB - Social selection offers an alternative to sexual selection by reversing its logic. Social selection starts with offspring production and works back to mating, and starts with behavioural dynamics and works up to gene pool dynamics. In social selection, courtship can potentially be deduced as a negotiation, leading to an optimal allocation of tasks during offspring rearing. Ornaments facilitate this negotiation and also comprise 'admission tickets' to cliques. Mating pairs may form 'teams' based on the reciprocal sharing of pleasure. The parent-offspring relation can be managed by the parent considered as the owner of a 'family firm' whose product is offspring. The cooperation in reproductive social behaviour evolves as a mutual direct benefit through individual selection rather than as some form of altruism requiring kin or multi-level selection. PMID- 22777016 TI - The evolution of female ornaments and weaponry: social selection, sexual selection and ecological competition. AB - Ornaments, weapons and aggressive behaviours may evolve in female animals by mate choice and intrasexual competition for mating opportunities-the standard forms of sexual selection in males. However, a growing body of evidence suggests that selection tends to operate in different ways in males and females, with female traits more often mediating competition for ecological resources, rather than mate acquisition. Two main solutions have been proposed to accommodate this disparity. One is to expand the concept of sexual selection to include all mechanisms related to fecundity; another is to adopt an alternative conceptual framework-the theory of social selection-in which sexual selection is one component of a more general form of selection resulting from all social interactions. In this study, we summarize the history of the debate about female ornaments and weapons, and discuss potential resolutions. We review the components of fitness driving ornamentation in a wide range of systems, and show that selection often falls outside the limits of traditional sexual selection theory, particularly in females. We conclude that the evolution of these traits in both sexes is best understood within the unifying framework of social selection. PMID- 22777018 TI - Family feuds: social competition and sexual conflict in complex societies. AB - Darwin was initially puzzled by the processes that led to ornamentation in males what he termed sexual selection-and those that led to extreme cooperation and altruism in complex animal societies-what was later termed kin selection. Here, I explore the relationships between sexual and kin selection theory by examining how social competition for reproductive opportunities-particularly in females-and sexual conflict over mating partners are inherent and critical parts of complex altruistic societies. I argue that (i) patterns of reproductive sharing within complex societies can drive levels of social competition and reproductive conflict not only in males but also in females living in social groups, and ultimately the evolution of female traits such as ornaments and armaments; (ii) mating conflict over female choice of sexual partners can influence kin structure within groups and drive the evolution of complex societies; and (iii) patterns of reproductive sharing and conflict among females may also drive the evolution of complex societies by influencing kin structure within groups. Ultimately, complex societies exhibiting altruistic behaviour appear to have only arisen in taxa where social competition over reproductive opportunities and sexual conflict over mating partners were low. Once such societies evolved, there were important selective feedbacks on traits used to regulate and mediate intra-sexual competition over reproductive opportunities, particularly in females. PMID- 22777019 TI - The sociobiology of sex: inclusive fitness consequences of inter-sexual interactions. AB - The diversity of social interactions between sexual partners has long captivated biologists, and its evolution has been interpreted largely in terms of 'direct fitness' pay-offs to partners and their descendants. Inter-sexual interactions also have 'indirect effects' by affecting the fitness of relatives, with important consequences for inclusive fitness. However, inclusive fitness arguments have received limited consideration in this context, and definitions of 'direct' and 'indirect' fitness effects in this field are often inconsistent with those of inclusive fitness theory. Here, we use a sociobiology approach based on inclusive fitness theory to distinguish between direct and indirect fitness effects. We first consider direct effects: we review how competition leads to sexual conflict, and discuss the conditions under which repression of competition fosters sexual mutualism. We then clarify indirect effects, and show that greenbeard effects, kin recognition and population viscosity can all lead to episodes of indirect selection on sexual interactions creating potential for sexual altruism and spite. We argue that the integration of direct and indirect fitness effects within a sociobiology approach enables us to consider a more diverse spectrum of evolutionary outcomes of sexual interactions, and may help resolving current debates over sexual selection and sexual conflict. PMID- 22777020 TI - The limits of sexual conflict in the narrow sense: new insights from waterfowl biology. AB - Sexual conflict occurs when the evolutionary interests of the sexes differ and it broadly applies to decisions over mating, fertilization and parental investment. Recently, a narrower view of sexual conflict has emerged in which direct selection on females to avoid male-imposed costs during mating is considered the distinguishing feature of conflict, while indirect selection is considered negligible. In this view, intersexual selection via sensory bias is seen as the most relevant mechanism by which male traits that harm females evolve, with antagonistic coevolution between female preferences and male manipulation following. Under this narrower framework, female preference and resistance have been synonymized because both result in a mating bias, and similarly male display and coercion are not distinguished. Our recent work on genital evolution in waterfowl has highlighted problems with this approach. In waterfowl, preference and resistance are distinct components of female phenotype, and display and coercion are independent male strategies. Female preference for male displays result in mate choice, while forced copulations by unpreferred males result in resistance to prevent these males from achieving matings and fertilizations. Genital elaborations in female waterfowl appear to function in reinforcing female preference to maintain the indirect benefits of choice rather than to reduce the direct costs of coercive mating. We propose a return to a broader view of conflict where indirect selection and intrasexual selection are considered important in the evolution of conflict. PMID- 22777021 TI - The evolution of optimal female mating rate changes the coevolutionary dynamics of female resistance and male persistence. AB - Mating decisions usually involve conflict of interests between sexes. Accordingly, males benefit from increased number of matings, whereas costs of mating favour a lower mating rate for females. The resulting sexual conflict underlies the coevolution of male traits that affect male mating success ('persistence') and female traits that affect female mating patterns ('resistance'). Theoretical studies on the coevolutionary dynamics of male persistence and female resistance assumed that costs of mating and, consequently, the optimal female mating rate are evolutionarily constant. Costs of mating, however, are often caused by male 'persistence' traits that determine mating success. Here, we present a model where the magnitude of costs of mating depend on, and evolve with, male persistence. We find that allowing costs of mating to depend on male persistence results in qualitatively different coevolutionary dynamics. Specifically, we find that male traits such as penis spikes that harm females are not predicted to exhibit runaway selection with female resistance, in contrast to previous theory that predicts indefinite escalation. We argue that it is essential to determine when and to what extent costs of mating are caused by male persistence in order to understand and accurately predict coevolutionary dynamics of traits involved in mating decisions. PMID- 22777022 TI - Looking for sexual selection in the female brain. AB - Female mate choice behaviour has significant evolutionary consequences, yet its mechanistic origins are not fully understood. Recent studies of female sensory systems have made great strides in identifying internal mechanisms governing female preferences. Only recently, however, have we begun to identify the dynamic genomic response associated with mate choice behaviour. Poeciliids provide a powerful comparative system to examine genomic responses governing mate choice and female preference behaviour, given the great range of mating systems: from female mate choice taxa with ornamental courting males to species lacking male ornamentation and exhibiting only male coercion. Furthermore, they exhibit laboratory-tractable preference responses without sexual contact that are decoupled from reproductive state, allowing investigators to isolate mechanisms in the brain without physiological confounds. Early investigations with poeciliid species (Xiphophorus nigrensis and Gambusia affinis) have identified putative candidate genes associated with female preference response and highlight a possible genomic pathway underlying female social interactions with males linked functionally with synaptic plasticity and learning processes. This network is positively correlated with female preference behaviour in the female mate choice species, but appears inhibited in the male coercive species. This behavioural genomics approach provides opportunity to elucidate the fundamental building blocks, and evolutionary dynamics, of sexual selection. PMID- 22777024 TI - Efficient scrambling-free synthesis of heteroleptic terbium triple-decker (porphyrinato)(crown-phthalocyaninates). AB - New heteroleptic triple-decker terbium complexes of general structure [Br(4)TPP]Tb[(15C5)(4)Pc]Tb[Br(4)TPP] (Tb-TD) and [Br(4)TPP]Tb[(15C5)(4)Pc]Tb[(15C5)(4)Pc] (Tb-TD*) (Br(4)TPP = tetrakis-meso-(4 bromophenyl)-porphyrin, (15C5)(4)Pc = tetra-(15-crown-5)-phthalocyanine) are synthesized with 48% and 57% yields, respectively. The triple-decker complexes were prepared by interaction of generated in situ terbium monoporphyrinate [Br(4)TPP]Tb(acac) and corresponding double-decker precursors. The heteroleptic double-decker precursor [Br(4)TPP]Tb[(15C5)(4)Pc] was prepared for the first time in a two step one-pot synthesis. No ligand scrambling was observed in the synthesis of Tb-TD, while 4% scrambling was determined in the case of Tb-TD*. High yields of target triple-decker complexes were achieved despite the presence of electron-donating crown-ether fragments with low thermal stability at the phthalocyanine deck. Analysis of lanthanide-induced paramagnetic shifts of protons of Tb-TD together with data of previously reported La, Pr, Nd and Eu analogues allowed precise separation of contributions of contact and dipolar lanthanide terms as well as verification of isostructurality of complexes within the series. PMID- 22777023 TI - Gene duplication, tissue-specific gene expression and sexual conflict in stalk eyed flies (Diopsidae). AB - Gene duplication provides an essential source of novel genetic material to facilitate rapid morphological evolution. Traits involved in reproduction and sexual dimorphism represent some of the fastest evolving traits in nature, and gene duplication is intricately involved in the origin and evolution of these traits. Here, we review genomic research on stalk-eyed flies (Diopsidae) that has been used to examine the extent of gene duplication and its role in the genetic architecture of sexual dimorphism. Stalk-eyed flies are remarkable because of the elongation of the head into long stalks, with the eyes and antenna laterally displaced at the ends of these stalks. Many species are strongly sexually dimorphic for eyespan, and these flies have become a model system for studying sexual selection. Using both expressed sequence tag and next-generation sequencing, we have established an extensive database of gene expression in the developing eye-antennal imaginal disc, the adult head and testes. Duplicated genes exhibit narrower expression patterns than non-duplicated genes, and the testes, in particular, provide an abundant source of gene duplication. Within somatic tissue, duplicated genes are more likely to be differentially expressed between the sexes, suggesting gene duplication may provide a mechanism for resolving sexual conflict. PMID- 22777027 TI - A few hours from disaster. PMID- 22777025 TI - Lay perspectives on hypertension and drug adherence: systematic review of qualitative research. AB - OBJECTIVE: To synthesise the findings from individual qualitative studies on patients' understanding and experiences of hypertension and drug taking; to investigate whether views differ internationally by culture or ethnic group and whether the research could inform interventions to improve adherence. DESIGN: Systematic review and narrative synthesis of qualitative research using the 2006 UK Economic and Social Research Council research methods programme guidance. DATA SOURCES: Medline, Embase, the British Nursing Index, Social Policy and Practice, and PsycInfo from inception to October 2011. STUDY SELECTION: Qualitative interviews or focus groups among people with uncomplicated hypertension (studies principally in people with diabetes, established cardiovascular disease, or pregnancy related hypertension were excluded). RESULTS: 59 papers reporting on 53 qualitative studies were included in the synthesis. These studies came from 16 countries (United States, United Kingdom, Brazil, Sweden, Canada, New Zealand, Denmark, Finland, Ghana, Iran, Israel, Netherlands, South Korea, Spain, Tanzania, and Thailand). A large proportion of participants thought hypertension was principally caused by stress and produced symptoms, particularly headache, dizziness, and sweating. Participants widely intentionally reduced or stopped treatment without consulting their doctor. Participants commonly perceived that their blood pressure improved when symptoms abated or when they were not stressed, and that treatment was not needed at these times. Participants disliked treatment and its side effects and feared addiction. These findings were consistent across countries and ethnic groups. Participants also reported various external factors that prevented adherence, including being unable to find time to take the drugs or to see the doctor; having insufficient money to pay for treatment; the cost of appointments and healthy food; a lack of health insurance; and forgetfulness. CONCLUSIONS: Non-adherence to hypertension treatment often resulted from patients' understanding of the causes and effects of hypertension; particularly relying on the presence of stress or symptoms to determine if blood pressure was raised. These beliefs were remarkably similar across ethnic and geographical groups; calls for culturally specific education for individual ethnic groups may therefore not be justified. To improve adherence, clinicians and educational interventions must better understand and engage with patients' ideas about causality, experiences of symptoms, and concerns about drug side effects. PMID- 22777026 TI - Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis. AB - OBJECTIVE: To determine the diagnostic accuracy of two "spot urine" tests for significant proteinuria or adverse pregnancy outcome in pregnant women with suspected pre-eclampsia. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Searches of electronic databases 1980 to January 2011, reference list checking, hand searching of journals, and contact with experts. INCLUSION CRITERIA: Diagnostic studies, in pregnant women with hypertension, that compared the urinary spot protein to creatinine ratio or albumin to creatinine ratio with urinary protein excretion over 24 hours or adverse pregnancy outcome. Study characteristics, design, and methodological and reporting quality were objectively assessed. DATA EXTRACTION: Study results relating to diagnostic accuracy were extracted and synthesised using multivariate random effects meta analysis methods. RESULTS: Twenty studies, testing 2978 women (pregnancies), were included. Thirteen studies examining protein to creatinine ratio for the detection of significant proteinuria were included in the multivariate analysis. Threshold values for protein to creatinine ratio ranged between 0.13 and 0.5, with estimates of sensitivity ranging from 0.65 to 0.89 and estimates of specificity from 0.63 to 0.87; the area under the summary receiver operating characteristics curve was 0.69. On average, across all studies, the optimum threshold (that optimises sensitivity and specificity combined) seems to be between 0.30 and 0.35 inclusive. However, no threshold gave a summary estimate above 80% for both sensitivity and specificity, and considerable heterogeneity existed in diagnostic accuracy across studies at most thresholds. No studies looked at protein to creatinine ratio and adverse pregnancy outcome. For albumin to creatinine ratio, meta-analysis was not possible. Results from a single study suggested that the most predictive result, for significant proteinuria, was with the DCA 2000 quantitative analyser (>2 mg/mmol) with a summary sensitivity of 0.94 (95% confidence interval 0.86 to 0.98) and a specificity of 0.94 (0.87 to 0.98). In a single study of adverse pregnancy outcome, results for perinatal death were a sensitivity of 0.82 (0.48 to 0.98) and a specificity of 0.59 (0.51 to 0.67). CONCLUSION: The maternal "spot urine" estimate of protein to creatinine ratio shows promising diagnostic value for significant proteinuria in suspected pre-eclampsia. The existing evidence is not, however, sufficient to determine how protein to creatinine ratio should be used in clinical practice, owing to the heterogeneity in test accuracy and prevalence across studies. Insufficient evidence is available on the use of albumin to creatinine ratio in this area. Insufficient evidence exists for either test to predict adverse pregnancy outcome. PMID- 22777028 TI - Magnetic resonance imaging of the lumbar spine. PMID- 22777029 TI - Should we screen for type 2 diabetes: Yes. PMID- 22777031 TI - Defeat of antipiracy treaty is hailed as victory for generic drugs. PMID- 22777030 TI - Should we screen for type 2 diabetes? No. PMID- 22777032 TI - Disruption to NHS could force doctors and managers to operate more sustainably, conference is told. PMID- 22777033 TI - Development and validation of two multiresidue liquid chromatography tandem mass spectrometry methods based on a versatile extraction procedure for isolating non steroidal anti-inflammatory drugs from bovine milk and muscle tissue. AB - The main difficulties in analysing non-steroidal anti-inflammatory drugs (NSAIDs) in food and biological samples are due to the tight non-covalent interactions established with matrix proteins and the amount of occurring fatty material. The present paper describes an effective extraction procedure able to isolate fifteen NSAIDs (acetaminophen, salicylic acid, ibuprofen, diclofenac, flunixin and its metabolite 5-hydroxy-flunixin, nimesulide, phenylbutazone, meclofenamic acid, tolfenamic acid, meloxicam, carprofen, ketoprofen, naproxen and etodolac) from bovine milk and muscle tissue through two succeeding steps: (a) deproteinisation/extraction with organic solvent, essential to lower the medium dielectric constant and, therefore, to release the analytes from matrix; (b) SPE clean-up on OASIS cartridges. Lipids were easily removed during low-temperature centrifugations. The advantages of the developed procedure pertain to the efficient removal of the fat substances (very low matrix effect and high recovery yields) and its versatility, since it can be applied both to milk and muscle with few adjustments due to the diversity of the two matrices. Ion-pairing reversed phase chromatography combined with the negative electrospray detection was able to achieve low detection capabilities (CCbetas) for all analytes and, in particular, for diclofenac whose Maximum Residue Limit (MRL) in milk is 0.1 MUg kg(-1). The methods were validated according to the guidelines of the Commission Decision 2002/657/EC and then applied for a small monitoring study. A number of samples showed traces of salicylic acid (SA), but its occurrence was not ascribed to a misuse of drugs (aspirin, salicylic acid) since SA, accumulating in plants in response to a pathogen attack, may be introduced into the food chain. PMID- 22777035 TI - Sensory reconstruction of a finger pulp defect using a dorsal homodigital island flap. AB - BACKGROUND: This article reports sensory reconstruction of a finger pulp defect using a dorsal homodigital island flap including double dorsal branches of the proper digital nerves. METHODS: From February of 2008 to December of 2009, the dorsal homodigital island flap was used in 15 fingers in 15 patients. The average patient age was 32 years. The injured digits included six index, six long, and three ring fingers. The mean size of the finger pulp defects was 2.4 * 2.0 cm, the mean flap size was 2.5 * 2.1 cm, and the mean pedicle length was 1.2 cm. Neurorrhaphy was performed between the dorsal branches of the proper digital nerves and the proper digital nerves at the recipient site. Flap sensation was assessed using static two-point discrimination and Semmes-Weinstein monofilament testing. For comparison, 28 patients treated using a cross-finger flap including a single nerve branch from February of 2005 to October of 2007 were included. RESULTS: In the study group, all flaps survived completely. At a mean follow-up of 19 months, the mean static two-point discrimination and Semmes-Weinstein monofilament scores on the pulp were 5.8 mm and 3.94, respectively. In the comparison group, the scores were 8.4 mm and 4.11, respectively. There was a significant difference between the two groups in static two-point discrimination and no significant difference in Semmes-Weinstein monofilament scores. CONCLUSIONS: The dorsal homodigital island flap is an alternative for finger pulp reconstruction. The authors suggest performing double neurorrhaphies to improve flap sensation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 22777036 TI - Intrinsic dynamics of the fat graft: in vitro interactions between the main cell actors. AB - BACKGROUND: Successful soft-tissue reconstruction requires autologous tissue transfer in respect to the increasingly important "replace like-with-like" principle. Autologous lipoaspirate material for fat grafting can easily be obtained in large amounts without substantial donor-site morbidity. The exact nature and fate of the different cells in the transplanted fat graft and their contribution to tissue reconstruction, however, remain largely unknown. METHODS: Adipose tissue was harvested from healthy female patients. CD34+ adipose-derived stem cells were isolated through magnetic-activated cell sorting and brought into co-culture with mature adipocytes in various culture medium conditions. Proliferation and differentiation of the adipose-derived stem cells were examined through histology, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and polymerase chain reaction assays. RESULTS: This study demonstrates that adipose-derived stem cells from fresh adipose tissue can be isolated within a few hours via magnetic-activated cell sorting with selection for CD34+ cells. All unpassaged adipose-derived stem cells in fresh adipose tissue are CD34+. Subsets include CD34+ CD31+ and CD34+ CD271+. No CD34+ CD45+ cells were present. Histological staining, polymerase chain reaction, and MTT assays confirm that purified mature adipose cells incite adipose-derived stem cells proliferation and adipose differentiation in vitro. CONCLUSIONS: This in vitro study demonstrates important interactions between the main actors in the adipose graft, the adipose-derived stem cells and the mature adipocytes. Although the eventual fate of these cells in a clinically implemented fat graft is still largely unknown, the results of this study support the theory that lipofilling can be conceived as an in vivo tissue engineering approach in which the mature adipocytes within fat grafts support proliferation and differentiation in the co grafted stromal cell population. PMID- 22777037 TI - Differential closure of the spheno-occipital synchondrosis in syndromic craniosynostosis. AB - BACKGROUND: The spheno-occipital synchondrosis is a driver of cranial base and facial growth. Its premature fusion has been associated with midface hypoplasia in animal models. The authors reviewed computed tomographic scans of patients with Apert and Muenke syndrome, craniosynostosis syndromes with midface hypoplasia, to assess premature fusion of the spheno-occipital synchondrosis when compared with normal controls. METHODS: Ninety head computed tomographic scans of Apert syndrome patients and 31 head scans of Muenke syndrome patients were assessed, in addition to an equal number of control scans. Spheno-occipital synchondrosis fusion on axial images was graded as open, partially closed, or closed. Analysis focused on ages 7 to 14 years, as no control patient fused before age 7 or had failed to fuse after age 14. RESULTS: All 38 Apert syndrome patients aged 7 to 14 had some degree of spheno-occipital synchondrosis closure, compared with 29 of 38 matched controls (p = 0.0023). Seventeen of 20 Muenke syndrome patients showed closure, compared with 14 of 20 matched controls (p = 0.4506). Partial fusion was seen as early as age 2 in Apert syndrome and age 6 in Muenke syndrome patients; the earliest fusion was seen at age 7 in the control group. CONCLUSIONS: Compared with matched controls, the spheno-occipital synchondrosis closes significantly earlier in patients with Apert syndrome but not Muenke syndrome. This correlates well to reported incidences of midface hypoplasia in these syndromes. Although causality cannot be concluded from this study, an association exists between midface phenotype and degree of spheno occipital synchondrosis closure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II. PMID- 22777038 TI - Defining the infratip lobule in rhinoplasty: anatomy, pathogenesis of abnormalities, and correction using an algorithmic approach. AB - BACKGROUND: Excess infratip lobule projection is often the result of deformities of the middle crus and lower lateral cartilage. The causes and correction of excess projection have not been well described. The classification of the deformities causing excess infratip lobule projection is defined and a surgical algorithm for addressing the infratip lobule is presented. METHODS: A retrospective review of primary rhinoplasties was combined with the use of a cadaver model to identify the causes of excess infratip lobule projection and develop an algorithm for its correction. Specific cases are presented to demonstrate the consistency and predictability of these techniques. RESULTS: The classification of excess infratip lobule projection is divided into intrinsic (i.e., long middle crus, wide middle crus, lower lateral malposition, and combination) and extrinsic causes (i.e., prominent septum). After correcting extrinsic causes, the algorithm progresses from medial to lateral, working from the medial crus to the lateral crus. Final refinement using transdomal sutures establishes the endpoint for infratip lobule projection and alar rim position when the cephalic and caudal edges (rotational orientation) of the lower lateral cartilage lie in the same plane. CONCLUSIONS: A simple classification and logical algorithm are established to help rhinoplasty surgeons achieve aesthetic and consistent infratip lobule projection in cosmetic rhinoplasty. Establishing appropriate infratip lobule projection is essential for an aesthetic result in the lower third of the nose. The appearance of this complex area with the tip, columella, ala, and lobule has great importance in the final outcome in rhinoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 22777039 TI - Long-term outcomes following fat grafting in prosthetic breast reconstruction: a comparative analysis. AB - BACKGROUND: Autologous fat grafting has become a common technique for optimizing aesthetic outcomes following breast reconstruction. Its long-term oncologic implications, however, remain unclear. The authors evaluated long-term outcomes following tissue expander breast reconstruction with and without fat grafting. METHODS: A retrospective review was performed of consecutive patients undergoing mastectomy with immediate tissue expander reconstruction from April of 1998 to August of 2008. Demographic, operative, oncologic, and postoperative factors were recorded, including the use of fat grafting. Mean follow-up was 42.1 +/- 28.8 and 43.6 +/- 27.2 months for non-fat-grafting and fat-grafting patients, respectively (p = 0.63), including 24.8 +/- 5.9 months after the first fat-grafting procedure. Fisher's exact test, t test, and regression analysis were used for statistics. RESULTS: A review of 886 patients (n = 1202 breasts) revealed no significant differences in demographics, operative characteristics, tumor staging, or radiation therapy exposure between fat-grafting (n = 90 breasts) and non-fat grafting (n = 1112 breasts) patients. Ninety-nine fat-grafting procedures were performed an average of 18.3 months after reconstruction, with one complication (fat necrosis). Grafting did not affect local tumor recurrence or survival when compared with non-fat-grafted breasts. Complication following reconstruction, including a poor cosmetic result, was an independent predictor of undergoing subsequent fat grafting (p < 0.0001). CONCLUSIONS: The analysis suggests that fat grafting after breast reconstruction does not adversely affect local tumor recurrence or survival on long-term follow-up. Autologous fat grafting can be used as an aesthetic adjunct to prosthetic reconstruction with minimal complications. These results also indicate the need for multi-institutional, prospective studies to definitively establish its oncologic safety. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 22777040 TI - Quality of life long-term after body contouring surgery following bariatric surgery: sustained improvement after 7 years. AB - BACKGROUND: Bariatric surgery for morbid obesity results in massive weight loss and improvement of health and quality of life. A downside of the major weight loss is the excess of overstretched skin, which may influence the patient's quality of life by causing functional and aesthetic problems. The purpose of the current study was to evaluate the patient's quality of life long-term after body contouring following bariatric surgery. METHODS: Quality of life was measured with the Obesity Psychosocial State Questionnaire in 33 post-bariatric surgery patients 7.2 years (range, 3.2 to 13.3 years) after body contouring surgery. Data were compared with previous assessments 4.1 years (range, 0.7 to 9.2 years) after body contouring surgery of the quality of life at that time and before body contouring surgery. RESULTS: Compared with appraisals of quality of life before body contouring surgery, a significant, mostly moderate to large, sustained improvement of quality of life was observed in post-bariatric surgery patients 7.2 years after body contouring surgery in six of the seven psychosocial domains. A small deterioration occurred between 4.1- and 7.2-year follow-up on two of the seven domains except for the domain efficacy toward eating, which showed a significant improvement. At 7-year follow-up, 18 patients (55 percent) were satisfied with the result of body contouring surgery. CONCLUSIONS: This study indicates a sustained quality-of-life improvement in post-bariatric surgery patients after body contouring surgery. This suggests the importance of including reconstructive surgery as a component in the multidisciplinary approach in the surgical treatment of morbid obesity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 22777042 TI - Characterization of a conjugate between Rose Bengal and chitosan for targeted antibiofilm and tissue stabilization effects as a potential treatment of infected dentin. AB - Bacterial biofilms and dentin structural changes are some of the major challenges in the management of infected dentin tissue. This study characterized a photosensitizer-conjugated chitosan with enhanced photodynamic efficacy against dental biofilms, as well as the ability to reinforce the postinfected dentin matrix in order to improve its mechanical and chemical stability. Rose Bengal conjugated chitosan (CSRB) was synthesized using a chemical cross-linking method and characterized for photophysical, photobiological, and cytotoxicity properties. Its potential as an antibacterial and matrix-reinforcing agent on dentin collagen was also evaluated. Enterococcus faecalis as planktonic and in vitro biofilms was treated with CSRB and photodynamically activated with 5 to 60 J/cm(2) green light. Dentin collagen was used for the CSRB cross-linking experiments and evaluated for chemical changes, resistance to enzymatic degradation, and mechanical properties. CSRB was a photosensitizer with efficient singlet oxygen yield. In vitro photoactivation gave higher fibroblast cell survival than did RB alone. CSRB showed significant antibiofilm photoinactivation (P < 0.01). The CSRB-cross-linked dentin collagen showed higher resistance to collagenase degradation and superior mechanical properties (P < 0.05). In summary, the photoactivated CSRB particles synthesized in this study may be a synergistic multifunctional treatment approach with lower cytotoxicity and effective antibiofilm activity as well as the ability to reinforce the dentin collagen to enhance resistance to degradation and improve mechanical properties. This may be a targeted treatment strategy to deal with infected dentin hard tissues in a clinical scenario, where both disinfection and structural integrity need to be addressed concomitantly. PMID- 22777041 TI - Safety and pharmacokinetics of the anti-orthopoxvirus compound ST-246 following a single daily oral dose for 14 days in human volunteers. AB - ST-246 is being evaluated as a treatment for pathogenic orthopoxvirus infections in humans. To this end, a phase 2, double-blind, randomized, placebo-controlled, multicenter trial was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of ST-246 when administered as a single daily oral dose (400 mg or 600 mg) for 14 days in fed adult volunteers. ST-246 was safe and well tolerated, with no deaths or serious adverse events reported during the study. There was a low incidence of treatment-emergent adverse events (TEAEs), the most common of which were mild nausea and headache. There were no clinically significant results from laboratory assessments, vital sign measurements, physical examinations, or electrocardiograms. The PK and dose proportionality of ST-246 were determined. The PK analysis showed that steady state was achieved by day 5 for the ST-246 400-mg treatment group and by day 6 for the 600-mg group. The dose proportionality analysis showed that the 400- and 600-mg ratio of dose normalized peak drug concentration in plasma (C(max)) and relative exposure for each dosing interval (AUC(tau)) ranged from 80% to 85%. However, the 90% confidence intervals did not include 1.0, so dose proportionality could not be concluded. Overall, ST-246 was shown to be safe, and the PK was predictable. These results support further testing of ST-246 in a multicenter pivotal clinical safety study for licensure application. PMID- 22777043 TI - Mature Pseudomonas aeruginosa biofilms prevail compared to young biofilms in the presence of ceftazidime. AB - Phenotypic tolerances to antibiotics of mature and young Pseudomonas aeruginosa PAO1 biofilms and released planktonic bacteria were compared for four antibiotics. Resistance levels were similar for gentamicin and ciprofloxacin but differed for ceftazidime and meropenem. beta-Lactamase mapping showed that, after 5 h of ceftazidime exposure, mature biofilms produced more beta-lactamase than young biofilms, facilitating the growth of released planktonic bacteria. This shows the importance of early treatment and choice of antibiotics for P. aeruginosa biofilm infections. PMID- 22777044 TI - Evaluation of clinical outcomes in patients with bloodstream infections due to Gram-negative bacteria according to carbapenem MIC stratification. AB - Predictive modeling suggests that actual carbapenem MIC results are more predictive of clinical patient outcomes than categorical classification of the MIC as susceptible, intermediate, or resistant. Some have speculated that current CLSI guidelines' suggested thresholds are too high and that clinical success is more likely if the MIC value is <=1 mg/liter for certain organisms. Patients treated with carbapenems and with positive blood cultures for Pseudomonas aeruginosa, Acinetobacter baumannii, or extended-spectrum beta-lactamase (ESBL) producing Gram-negative bacteria were considered for evaluation in this clinical retrospective cohort study. Relevant patient demographics and microbiologic variables were collected, including carbapenem MIC. The primary objective was to define a risk-adjusted all-cause hospital mortality breakpoint for carbapenem MICs. Secondarily, we sought to determine if a similar breakpoint existed for indirect outcomes (e.g., time to mortality and length of stay [LOS] postinfection for survivors). Seventy-one patients met the criteria for study inclusion. Overall, 52 patients survived, and 19 died. Classification and regression tree (CART) analysis determined a split of organism MIC between 2 and 4 mg/liter and predicted differences in mortality (16.1% versus 76.9%; P < 0.01). Logistic regression controlling for confounders identified each imipenem MIC doubling dilution as increasing the probability of death 2-fold (adjusted odds ratio [aOR] 2.0; 95% confidence interval [CI], 1.3 to 3.2). Secondary outcomes were similar between groups. This study revealed that patients with organisms that had a MIC of >=4 mg/liter had worse outcomes than patients whose isolates had a MIC of <=2 mg/liter, even after adjustment for confounding variables. We recommend additional clinical studies to better understand the susceptibility breakpoint for carbapenems. PMID- 22777045 TI - Feasibility of a fixed-dose regimen of pyrazinamide and its impact on systemic drug exposure and liver safety in patients with tuberculosis. AB - Historically, dosing regimens for the treatment of tuberculosis (TB) have been proposed in an empirical manner. Dose selection has often been the result of efficacy trials in which drugs were administered regardless of the magnitude of the effect of demographic factors on drug disposition. This has created challenges for the prescription of fixed-dose combinations with novel therapeutic agents. The objectives of this investigation were to evaluate the impact of body weight on the overall systemic exposure to pyrazinamide (PZA) and to assess whether the use of one fixed dose, without adjustment according to weight, would ensure target exposure and safety requirements across the overall patient population. Using a population pharmacokinetic model, simulation scenarios were explored based on population demographics from clinical trials in TB patients and on historical hepatotoxicity data. The systemic drug exposure (area under the concentration-time curve [AUC]), peak concentrations (the maximum concentration of drug in serum [C(max)]), the time above the MIC (t > MIC), and the risk of hepatotoxicity were evaluated for the current weight-banded regimen and compared to fixed doses under the assumption that pharmacokinetic differences are the primary drivers of toxicity. Evaluation of the standard weight banding reveals that more than 50% of subjects in the weight range of 45 to 55 kg remain below the proposed target exposure to PZA. In contrast, the use of a fixed 1,500-mg dose resulted in a lower proportion of subjects under the target value, with a 0.2% average overall increase in the risk of hepatotoxicity. Our results strongly support the use of a fixed-dose regimen for PZA in coformulation or combination with novel therapeutic agents. PMID- 22777046 TI - Compared to subcutaneous tenofovir, oral tenofovir disoproxyl fumarate administration preferentially concentrates the drug into gut-associated lymphoid cells in simian immunodeficiency virus-infected macaques. AB - To compare tissue-based pharmacokinetics and efficacy of oral tenofovir disoproxyl fumarate (TDF) versus subcutaneous tenofovir (TFV), macaques were treated for 2 weeks starting 1 week after simian immunodeficiency virus inoculation. Despite lower plasma TFV levels in the oral TDF arm, similar TFV diphosphate levels and antiviral activities were measured in lymphoid cells of most tissues. In intestinal tissues, however, oral TDF resulted in higher active drug levels, associated with lower virus levels and better immune preservation. PMID- 22777047 TI - Role of oxidative stress in persister tolerance. AB - Persisters are dormant phenotypic variants of regular cells that are tolerant to antibiotics and play an important role in recalcitrance of chronic infections to therapy. Persisters can be produced stochastically in a population untreated with antibiotics. At the same time, a deterministic component of persister formation has also been documented in a population of cells with DNA damaged by fluoroquinolone treatment. Expression of the SOS response under these conditions induces formation of persisters by increasing expression of the TisB toxin. This suggests that other stress responses may also contribute to persister formation. Of particular interest is oxidative stress that pathogens encounter during infection. Activated macrophages produce reactive oxygen and nitrogen species which induce the SoxRS and OxyR regulons. Genes controlled by these regulons deactivate the oxidants and promote repair. We examined the ability of oxidative stress induced by paraquat (PQ) to affect persister formation. Preincubation of cells with PQ produced a dramatic increase in the number of persisters surviving challenge with fluoroquinolone antibiotics. PQ did not affect killing by kanamycin or ampicillin. Persisters in a culture treated with PQ that survived a challenge with a fluoroquinolone were also highly tolerant to other antibiotics. PQ induces SoxRS, which in turn induces expression of the AcrAB-TolC multidrug resistant (MDR) pump. Fluoroquinolones are extruded by this MDR pump, and the effect of PQ on antibiotic tolerance was largely abolished in a mutant that was defective in the pump. It appears that PQ, acting through AcrAB-TolC, reduces the concentration of fluoroquinolones in the cells. This allows a larger fraction of cells to become persisters in the presence of a fluoroquinolone. Analysis of a lexA3 mutant indeed showed a dependence of persister induction under these conditions on SOS. These findings show that induction of a classical resistance mechanism, MDR efflux, by oxidative stress leads to an increase in multidrug tolerant persister cells. PMID- 22777048 TI - Pharmacological characterization, structural studies, and in vivo activities of anti-Chagas disease lead compounds derived from tipifarnib. AB - Chagas disease, caused by the protozoan pathogen Trypanosoma cruzi, remains a challenging infection due to the unavailability of safe and efficacious drugs. Inhibitors of the trypanosome sterol 14alpha-demethylase enzyme (CYP51), including azole antifungal drugs, are promising candidates for development as anti-Chagas disease drugs. Posaconazole is under clinical investigation for Chagas disease, although the high cost of this drug may limit its widespread use. We have previously reported that the human protein farnesyltransferase (PFT) inhibitor tipifarnib has potent anti-T. cruzi activity by inhibiting the CYP51 enzyme. Furthermore, we have developed analogs that minimize the PFT-inhibitory activity and enhance the CYP51 inhibition. In this paper, we describe the efficacy of the lead tipifarnib analog compared to that of posaconazole in a murine model of T. cruzi infection. The plasma exposure profiles for each compound following a single oral dose in mice and estimated exposure parameters after repeated twice-daily dosing for 20 days are also presented. The lead tipifarnib analog had potent suppressive activity on parasitemia in mice but was unsuccessful at curing mice, whereas posaconazole as well as benznidazole cured 3 of 5 and 4 of 6 mice, respectively. The efficacy results are consistent with posaconazole having substantially higher predicted exposure than that of the tipifarnib analog after repeat twice-daily administration. Further changes to the tipifarnib analogs to reduce plasma clearance are therefore likely to be important. A crystal structure of a trypanosomal CYP51 bound to a tipifarnib analog is reported here and provides new insights to guide structure-based drug design for further optimized compounds. PMID- 22777049 TI - A whole-cell phenotypic screening platform for identifying methylerythritol phosphate pathway-selective inhibitors as novel antibacterial agents. AB - Isoprenoid biosynthesis is essential for survival of all living organisms. More than 50,000 unique isoprenoids occur naturally, with each constructed from two simple five-carbon precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Two pathways for the biosynthesis of IPP and DMAPP are found in nature. Humans exclusively use the mevalonate (MVA) pathway, while most bacteria, including all Gram-negative and many Gram-positive species, use the unrelated methylerythritol phosphate (MEP) pathway. Here we report the development of a novel, whole-cell phenotypic screening platform to identify compounds that selectively inhibit the MEP pathway. Strains of Salmonella enterica serovar Typhimurium were engineered to have separately inducible MEP (native) and MVA (nonnative) pathways. These strains, RMC26 and CT31-7d, were then used to differentiate MVA pathway- and MEP pathway-specific perturbation. Compounds that inhibit MEP pathway-dependent bacterial growth but leave MVA dependent growth unaffected represent MEP pathway-selective antibacterials. This screening platform offers three significant results. First, the compound is antibacterial and is therefore cell permeant, enabling access to the intracellular target. Second, the compound inhibits one or more MEP pathway enzymes. Third, the MVA pathway is unaffected, suggesting selectivity for targeting the bacterial versus host pathway. The cell lines also display increased sensitivity to two reported MEP pathway-specific inhibitors, further biasing the platform toward inhibitors selective for the MEP pathway. We demonstrate development of a robust, high-throughput screening platform that combines phenotypic and target-based screening that can identify MEP pathway selective antibacterials simply by monitoring optical density as the readout for cell growth/inhibition. PMID- 22777051 TI - Mainstreaming one health. PMID- 22777050 TI - Human cytomegalovirus inhibition by cardiac glycosides: evidence for involvement of the HERG gene. AB - Infection with human cytomegalovirus (HCMV) continues to be a major threat for pregnant women and the immunocompromised population. Although several anti-HCMV therapies are available, the development of new anti-HCMV agents is highly desired. There is growing interest in identifying compounds that might inhibit HCMV by modulating the cellular milieu. Interest in cardiac glycosides (CG), used in patients with congestive heart failure, has increased because of their established anticancer and their suggested antiviral activities. We report that the several CG--digoxin, digitoxin, and ouabain--are potent inhibitors of HCMV at nM concentrations. HCMV inhibition occurred prior to DNA replication, but following binding to its cellular receptors. The levels of immediate early, early, and late viral proteins and cellular NF-kappaB were significantly reduced in CG-treated cells. The activity of CG in infected cells correlated with the expression of the potassium channel gene, hERG. CMV infection upregulated hERG, whereas CG significantly downregulated its expression. Infection with mouse CMV upregulated mouse ERG (mERG), but treatment with CG did not inhibit virus replication or mERG transcription. These findings suggest that CG may inhibit HCMV by modulating human cellular targets associated with hERG and that these compounds should be studied for their antiviral activities. PMID- 22777052 TI - A 'cold-case' review of historic aboriginal and European-Australian encounters with toxic blooms of cyanobacteria. AB - Interest in preserving the cultural knowledge of Aboriginal Australians continues to rise. Various studies have erupted which aim to redefine knowledge that was once lost or obscured in writing and hitherto ignored. Recognising and acknowledging the traditional Aboriginal knowledge of the Australian environment helps to strengthen Aboriginal identity and gives credibility to the rising paradigm of ecotechnology in historic pre-European Australia. This review aims to establish knowledge of a traditional awareness of factors leading towards eutrophication in water resource management. Journals from pioneering explorers were examined for evidence of cyanobacterial blooms and examples of Aboriginal water resource management practices that aimed at avoiding health threats from poor water quality. Some cultural practices, focused on water resource management, are discussed with brief mentioned of the Waugal. It is concluded that in some cases the incorporation of scientific laws into mythology is a form of conceptual modelling compatible with science if examined carefully. PMID- 22777053 TI - Neither neoadjuvant nor adjuvant therapy increases survival after biliary tract cancer resection with wide negative margins. AB - BACKGROUND: We investigated the role of neoadjuvant/adjuvant therapies on survival for resectable biliary tract cancer. We hypothesized that neoadjuvant and adjuvant therapy should improve the survival probability in these patients. METHODS: This was a retrospective review of a prospective database of patients resected for gallbladder cancer (GBC) and cholangiocarcinoma (CC). One hundred fifty-seven patients underwent resection for primary GBC (n = 63) and CC (n = 94). Fisher's exact test, Student's t test, the log-rank test, and a Cox proportional hazard model determined significant differences. RESULTS: The 5-year overall survival rate after resection of GBC and CC was 50.6 % and 30.4 %, respectively. Of the patients, 17.8 % received neoadjuvant chemotherapy, 48.7 % received adjuvant chemotherapy, while 15.8 % received adjuvant chemoradiotherapy. Patients with negative margins of at least 1 cm had a 5-year survival rate of 52.4 % (p < 0.01). Adjuvant therapy did not significantly prolong survival. Neoadjuvant therapy delayed surgical resection on average for 6.8 months (p < 0.0001). Immediate resection increased median survival from 42.3 to 53.5 months (p = 0.01). CONCLUSIONS: Early surgical resection of biliary tract malignancies with 1 cm tumor-free margins provides the best probability for long-term survival. Currently available neoadjuvant or adjuvant therapy does not improve survival. PMID- 22777054 TI - Refinement of minimally invasive esophagectomy techniques after 15 years of experience. AB - INTRODUCTION: [corrected] In an effort to reduce the morbidity and mortality associated with open esophagectomy, a minimally invasive approach to esophagectomy was introduced at the University of Pittsburgh Medical Center (UPMC) in 1996. The objective of this article is to discuss the optimization and refinement of minimally invasive esophagectomy (MIE) techniques over the 15-year experience at UPMC. We also reviewed the literature on technical improvements in MIE. METHOD: Literature highlights for MIE and related meta-analyses comparing open esophagectomy and MIE were reviewed. The rationale and outcomes of techniques refinements were discussed in detail. RESULTS: Most meta-analyses and systematic reviews confirm the feasibility and safety of MIE and suggest similar oncologic outcomes as compared with open esophagectomy. Since 1996, over 1,000 minimally invasive esophagectomies have been performed at UPMC. We have made several refinements to the MIE procedure that we believe significantly improved our surgical outcomes. It included adjustment of width of the gastric conduit, application of omental flap, and conversion from minimally invasive, three-hole esophagectomy to minimally invasive Ivor Lewis esophagectomy. CONCLUSION: MIE became a mainstay in the surgical treatment of esophageal cancer at UPMC. The technical improvements detailed above make the UPMC approach to MIE a feasible, safe, and efficient procedure. PMID- 22777055 TI - Methodological and ethical quality of randomized controlled clinical trials in gastrointestinal surgery. AB - BACKGROUND: The randomized controlled trial (RCT) is the gold standard tool used to evaluate therapeutic interventions. Methodological and ethical aspects should be adequately reported to enable readers to make informed and justified judgments regarding the validity of a trial and the treatment effectiveness. OBJECTIVE: The aim of this study was to evaluate the methodological and ethical qualities of randomized clinical trials in gastrointestinal surgery and to assess the relationship between these two qualities. STUDY DESIGN: All of the articles chosen for review reported on phase III randomized controlled gastrointestinal surgical trials were published in 12 international journals during 2006 and 2007. The eligible studies were identified, selected, and then evaluated based on a broad set of predetermined criteria. The methodological quality was evaluated using the Jadad scale, and the ethical quality was evaluated using the Berdeu score. RESULTS: The mean Jadad score was 9.7 +/- 1.78. The methodological quality was insufficient in 64 RCTs (37.4 %; Jadad score <9). The mean Berdeu score was 0.36 +/- 0.08. The journal impact factor, number of randomized patients, and number of centers correlated with the outcome of the Jadad score, and the journal impact factor, industry funding, and year in which the trial began correlated with the outcome of the Berdeu score. Informed consent from patients was not obtained in 7 % (n = 12) of the RCTs, and research ethics committee approval was not mentioned in 14.6 % (n = 25) of the RCTs. CONCLUSIONS: The reporting of gastrointestinal surgery RCTs is less than optimal. In our study, the trials of higher methodological quality were more likely to provide information about their ethical aspects. These results suggest the need for more attention to be paid to the conduct of clinical research and the reporting of ethical aspects. The appropriation of the ethical rules by surgeons involved in human clinical trials could improve the methodology and reporting of RCTs in gastrointestinal surgery. PMID- 22777057 TI - Lung cancer: locally advanced NCSLC in the elderly: which treatment? PMID- 22777056 TI - Acute appendicitis in patients with end-stage renal disease. AB - BACKGROUND: Acute appendicitis in patients with end-stage renal disease (ESRD) poses a diagnostic challenge. Delayed surgery can contribute to higher morbidity and mortality rates. However, few studies have evaluated this disease among ESRD patients. Our study focused on the lack of data on the incidence and risk factors of acute appendicitis among ESRD patients and compared the outcomes in patients who underwent different dialysis modalities. METHODS: This national survey was conducted between 1997 and 2005 and included ESRD patients identified from the Taiwan National Health Insurance database. The incidence rate of acute appendicitis in ESRD patients was compared with that in randomly selected age-, sex-, and Charlson comorbidity score-matched non-dialysis controls. A Cox regression hazard model was used to identify risk factors. RESULTS: Among 59,781 incident ESRD patients, matched one-to-one with controls, there were 328 events of acute appendicitis. The incidence rate of 16.9 per 10,000 person-years in the ESRD cohort was higher than that in the control cohort (p = 0.003). The independent risk factors were atrial fibrillation (hazard ratio [HR], 2.08), severe liver disease (HR, 1.74), diabetes mellitus (HR, 1.58), and hemodialysis (HR, 1.74). Compared with the control cohort, subsequent perforation and mortality rates of acute appendicitis were also higher in the ESRD cohorts. There was no effect of dialysis modality on the patient outcomes. CONCLUSIONS: ESRD patients had a higher risk for acute appendicitis and poorer outcomes than non dialysis populations. A careful examination of ESRD patients presenting with atypical abdominal pain to avoid misdiagnosis is extremely important to prevent delayed surgery. PMID- 22777058 TI - Tumour molecular profiling for deciding therapy-the French initiative. AB - The use of tumour molecular profiles for therapeutic decision making requires that molecular diagnostics be introduced into routine clinical practice. To this end, the French National Cancer Institute and French Ministry of Health have set up a national network of 28 regional molecular genetics centres. These facilities perform selected molecular tests, free of charge, for all patients in their region, regardless of the institution where they are treated. A specific programme has also been implemented to anticipate the launch of new targeted treatments and reduce time-to-access to new drugs and experimental therapies. In 2011, 55,000 patients with cancer in France benefited from molecular predictive tests. The French nationwide initiative for tumour molecular profiling is a tool to fight inequalities in access to molecular testing and targeted therapy, and demonstrates that molecular stratification of tumours for therapeutic decisions is a cost-effective strategy that can be successfully integrated into the health care system. PMID- 22777059 TI - Targeted therapies: match-and-mix or match-and-miss? PMID- 22777061 TI - Letter from the editors. PMID- 22777062 TI - Reactivity of alpha-amino-peroxyl radicals and consequences for amine oxidation chemistry. AB - A comparative theoretical study is presented on the formation and fate of alpha amino-peroxyl radicals, recently proposed as important intermediates in the aerobic oxidation of amines. After radical abstraction of the weakly bonded alphaH-atom in the amine substrate, the alpha-amino-alkyl radical reacts irreversibly with O(2), forming the corresponding alpha-amino-peroxyl radical. HO(2)-elimination from various types of alpha-amino-peroxyl radicals (forming the corresponding imine) and the kinetically competing substrate H-abstraction (forming the alpha-amino-hydroperoxide) were computationally characterized. Polar solvents were found to reduce the HO(2)-elimination barrier, but increase the barrier for H-abstraction. Depending on the reaction conditions (gas or liquid phase, amine concentration, nature of the solvent, and temperature), either of the two mechanisms is favored. The consequences for aerobic amine oxidation chemistry are discussed. PMID- 22777063 TI - Lanthanide amidinates and guanidinates in catalysis and materials science: a continuing success story. AB - Today the rare-earth elements play a critical role in numerous high-tech applications. This is why various areas of rare-earth chemistry are currently thriving. In organolanthanide chemistry the search for new ligand sets which are able to satisfy the coordination requirements of the large lanthanide cations continues to be a hot topic. Among the most successful approaches in this field is the use of amidinate and guanidinate ligands of the general types [RC(NR')(2)](-) (R = H, alkyl, aryl; R' = alkyl, cycloalkyl, aryl, SiMe(3)) and [R(2)NC(NR')(2)](-) (R = alkyl, SiMe(3); R' = alkyl, cycloalkyl, aryl, SiMe(3)), which can both be regarded as steric cyclopentadienyl equivalents. Mono-, di- and trisubstituted lanthanide amidinate and guanidinate complexes are all readily available. Various rare earth amidinates and guanidinates have turned out to be very efficient homogeneous catalysts e.g. for the polymerization of olefins and dienes, the ring-opening polymerization of cyclic esters or the guanylation of amines. Moreover, certain alkyl-substituted lanthanide tris(amidinates) and tris(guanidinates) were found to be highly volatile and are thus promising precursors for ALD (= atomic layer deposition) and MOCVD (= metal-organic chemical vapor deposition) processes in materials science, e.g. for the production of lanthanide nitride thin layers. This tutorial review covers the continuing success story of lanthanide amidinates and guanidinates which have undergone an astonishing transition from mere laboratory curiosities to efficient homogeneous catalysts as well as ALD and MOCVD precursors within the past 10 years. PMID- 22777060 TI - Thrombosis and cancer. AB - Venous thromboembolism (VTE) is a potentially life-threatening condition that can be associated with significant morbidity. Thrombosis and cancer are linked by numerous pathophysiological mechanisms; the frequency of VTE and the recurrence rate are increased in the cancer population in comparison with other patient groups. VTE is the second most common cause of death in patients with cancer, but can also be the initial presenting complaint in patients with an occult malignancy. Risk factors for cancer-related VTE include tumour type, surgery, chemotherapy and the use of central venous catheters; predictors of VTE for individuals are only now beginning to emerge. Patients with cancer who develop symptomatic VTE during chemotherapy are at a greater risk of early mortality than those without VTE. The apparent impact of VTE on early mortality in patients with cancer raises the question of whether anticoagulation might improve long-term survival in this population, by direct tumour biology-modifying mechanisms. There are widely published guidelines that highlight the benefits of effective VTE strategies in patients with cancer. In partnership with the patient and their carers, the clinical team can improve patient outcomes with optimal risk assessment and concordance with national and international guidelines in the prophylaxis and treatment of VTE. PMID- 22777065 TI - Distribution of telomeric DNA sequences on the X-radiation-induced chromosome fragments observed in the genome of androgenetic brook trout (Salvelinus fontinalis, Mitchill 1814). AB - Cytogenetic screening of the androgenetic brook trout (Salvelinus fontinalis, Mitchill 1814) offspring hatched from eggs exposed to 420 Gy of X-radiation before insemination exhibited residues of the irradiated maternal nuclear genome in the form of small chromosome fragments. Remnants of the irradiated chromosomes had different sizes, and their number varied intraindividually from 1 to 15. To efficiently pass through the series of the cell divisions, such chromosome fragments must have had functional kinetochores. Distribution patterns of the telomeric hybridization signals on the chromosome fragments enabled us to distinguish their 3 groups: (i) telomere-less ring chromosomes with fused broken chromosome arms, (ii) rings formed in the course of fusion of the radiation broken chromosome arm with the opposite telomeric region and exhibiting interstitial telomeric signals at the fusion point, and (iii) chromosome fragments with fused unprotected sister chromatids of 1 broken arm and intact telomeres from the other arm. Disturbances during segregation of such fragments, mainly breakages during anaphase, may partially explain intraindividual variation in the number and size of the chromosome fragments observed in the androgenetic brook trout. PMID- 22777066 TI - Fructose-1,6-bisphosphate and N-acetylcysteine attenuate the formation of advanced oxidation protein products, a new class of inflammatory mediators, in vitro. AB - The accumulation of advanced oxidation protein products (AOPP) has been linked to several pathological conditions. Previous studies have identified AOPP as a novel biomarker of oxidative damage to proteins and a novel class of mediator of inflammation. The aim of this study was to determine the effects of fructose-1,6 bisphosphate (FBP) and N-acetylcysteine (NAC) as well as the synergistic effect of both treatments on the formation of AOPP in vitro. For this purpose, we incubated the human serum albumin (HSA) with various hypochlorous acid (HOCl) concentrations to produce albumin-advanced oxidation protein products (HSA-AOPP). Both FBP and NAC were capable of inhibiting the formation of HOCl-induced AOPP in a concentration-dependent manner. The synergistic effect promoted by the association of these drugs showed to be more effective than when tested alone. Thus, both FBP and NAC may be good candidates to mitigate and neutralize pro inflammatory and pro-oxidant effects of AOPP in several diseases. PMID- 22777067 TI - Cytokine profile in patients undergoing minimally invasive surgery with balanced anesthesia. AB - Patients undergoing surgical procedure develop an inflammatory response due to surgical trauma that may be modulated by anesthetics. The aim of this study was to investigate the cytokine profile in the plasma of adult patients who underwent minimally invasive surgery with balanced anesthesia with propofol, fentanyl, and sevoflurane. The study included 15 healthy patients scheduled for tympanoplasty or septoplasty under balanced anesthesia. Blood samples were drawn at four time points: before anesthesia, before surgery, 120 min after anesthesia induction, and on the first postoperative day. Plasma interleukin (IL)-1beta, -2, -4, -6, 8, -10, -12, TNF-alpha, and INF-gamma levels were assessed by flow cytometry. IL 6 levels were elevated on the day after the surgery (p < 0.001). All other cytokines did not change either during or after balanced anesthesia (p > 0.05). In conclusion, balanced anesthesia with propofol, fentanyl, and sevoflurane anesthesia is not associated with intraoperative changes in the plasma cytokines in healthy patients undergoing minimally invasive otorhinological surgeries. Considering IL-6 results, a postoperative inflammatory response may have occurred due to surgical stress. PMID- 22777068 TI - [New kinase inhibitors]. AB - Treatment of rheumatoid arthritis (RA) has dramatically changed during the last 15 years. A limited number of conventional disease-modifying antirheumatic drugs (DMARD) in combination with non-steroid anti-inflammatory drugs (NSAID) and corticosteroids are facing a variety of biologics that are increasingly being used. Because of the high costs of biologics as well as the necessity for subcutaneous or intravenous administration, there is currently a growing interest in new and potent oral compounds such as the small molecules. Inflammatory pathways and mechanisms in signal transduction have been characterized in detail. Instead of neutralizing the action of a proinflammatory cytokine by antagonizing its biologic effect by an antibody, these small molecules interfere with the intracellular pathways of the inflammatory cascade. Intracellular kinases are among these enzymes which are crucially involved in intracellular signal transduction. Kinase inhibitors have been successfully used within the last few years in the treatment of various hematological malignancies, such as imatinib in patients with chronic myeloid leukemia. More recently, the Janus kinase (JAK) inhibitor tofacitinib has been evaluated as a potential new treatment option in RA and is awaiting approval. While an overview about JAK inhibition will be given elsewhere, other inhibitors such as spleen tyrosine kinase (Syk) inhibitor, mitogen-activated protein kinase (MAPK) inhibitor and Bruton's tyrosine kinase (Btk) inhibitor are currently in preclinical and clinical development. PMID- 22777069 TI - Electrophysiological effects of lysophosphatidylcholine on HL-1 cardiomyocytes assessed with a microelectrode array system. AB - BACKGROUND: Sudden death due to malignant ventricular arrhythmias is the most important cause of death in acute myocardial infarction. Improved knowledge about the pathophysiology underlying these arrhythmias is essential in the search for new anti-arrhythmic strategies. Lysophosphatidylcholine (LPC), a hydrolysis product of (membrane) phospholipid degradation, is one of the most potent pro arrhythmic substances that accumulate in the human heart during myocardial ischemia. The aim of this study was to set up and validate an in vitro experimental system for studies on the effects of LPC on electrophysiological parameters in beating cardiomyocytes. METHODS AND RESULTS: Spontaneously beating HL-1 cardiomyocytes were cultured on multielectrode array microchips for three days for the recording of electrical activities in the form of field potentials (FP). FPs were recorded at baseline and after addition of 2, 4, 8, 12, 16, 20, and 24 uM of LPC to the cell medium (n=9). We found that LPC could induce rapid effects on electrical parameters in the HL-1 cells. The overall half-maximal effective concentration (EC(50)) of LPC was around 12 uM. The beating rate and peak-peak amplitude of FP thus decreased at concentrations >= 12 uM and were inversely proportional to increased LPC concentration. The duration of FP was significantly prolonged with LPC above 12 uM and was concentration-dependent. LPC delayed signal propagation, an effect which was mimicked by blocking gap junctions with heptanol and attenuated by pre-treatment with isoprenaline and atropine. Finally, asynchronous activity was induced by LPC at >12 uM. CONCLUSIONS: LPC induced prompt and pronounced electrophysiological alterations that may underlie its observed pro-arrhythmic properties. Our in vitro model with HL-1 cells and microelectrode array system may be a useful tool for preclinical studies of electrophysiological effects of various pathophysiological concepts. PMID- 22777070 TI - Multiplex mutation screening by mass spectrometry in gastrointestinal stromal tumours. AB - AIMS: Clinical decision making and optimal clinical trial design based on cancer genetic information will be increasingly informed by the mutational status of multiple genes. METHODS: We performed mutation screening on 22 fresh frozen gastrointestinal stromal tumours (GISTs) using a multiplexed oncogene screening panel with a mass spectroscopy readout (MassARRAY). The panel can detect 390 known mutations across 30 genes, including several known to contribute to intracellular signalling in cancers (BRAF, PIK3CA, KRAS HRAS, NRAS, AKT1, CTNNB1, GNAQ, CDK4, MAP2K1 and MAP2K2). RESULTS: Direct Sanger sequencing confirmed that 16 cases (73%) harboured KIT mutations, affecting exon 11, 13 and 17, and the remaining six were wild-type for both KIT and PDGFRA. The sensitivity of the multiplexed oncogene screening panel was 100% for identifying missense mutations in KIT. Only 17% of the deletion mutations were detected, because the panel was not designed for detecting these. A substitution in FBX4 exon 1 (S8R), representing a germline single-nucleotide polymorphism, was observed in a case with KIT exon 11 missense mutation. No other mutations were identified, including in the six wild-type GISTs. CONCLUSIONS: Our results indicate that mutations other than KIT or PDGFRA are rare in GISTs. Although multiplex mutation screening by mass spectrometry detected missense mutations accurately, it is not sufficient to screen mutations because deletion mutations are common in GISTs. PMID- 22777071 TI - MDS with del(5q) and associated cKIT D816V positive mastocytosis. PMID- 22777072 TI - Subareolar abscess in a male breast: cytological characterisation and distinction from other benign and malignant squamous cell aspirate. PMID- 22777073 TI - NSAID-associated protein losing enteropathy with fatal outcome. PMID- 22777074 TI - Recently described and unusual variants of urothelial carcinoma of the urinary bladder. AB - Urothelial carcinoma (UC) of the urinary bladder has a great propensity to undergo divergent differentiation. The resulting subtypes are morphologically unique and have significant prognostic and therapeutic differences. While squamous and glandular subtypes are the most common, a number of other well characterised morphological subtypes were described in the 2004 World Health Organization Classification. More recently additional variants of UC have been described, while others have been more fully characterised. In this review we report the details of recently described and selected unusual variants of UC. Specifically, the pathological and clinical details are discussed, relating to large nested and nested variant of UC, large cell undifferentiated carcinoma, lymphoepithelioma-like carcinoma, osteoclast rich undifferentiated carcinoma, pleomorphic giant cell carcinoma, UC with syncytiotrophoblastic giant cells, lipid cell variant of UC, micropapillary UC, UC with abundant myxoid stroma and plasmacytoid UC. PMID- 22777076 TI - Synchronous occurrence of a hemorrhagic hypothalamic hamartoma and a suprasellar teratoma. AB - Hypothalamic hamartomas have been reported to coexist with lesions like Rathke's cleft cyst and arachnoid cysts in the suprasellar or temporo-sylvian regions. This is the first report in indexed literature describing its association with a suprasellar teratoma. A 7-year-old girl presented with long-standing precocious puberty and generalized tonic-clonic seizures and recent-onset raised intracranial pressure. MRI done prior to the onset of symptomatic raised intracranial pressure revealed 2 distinct lesions in the suprasellar region. One was a midline, pedunculated lesion arising from the hypothalamus, with evidence of an old bleed within it. A separate lesion, with a wide base near the tuberculum sellae and a posteriorly directed conical tip, was noted in an adjacent sagittal cut. CT scan done at the time of admission demonstrated a re bleed in the suprasellar region with blood in the lateral and third ventricles and gross hydrocephalus. The child was taken up for a ventriculoperitoneal shunt followed by complete excision of the lesions. Histopathologic examination confirmed the pedunculated lesion to be a hypothalamic hamartoma with evidence of hemorrhage, and the other to be a mature teratoma. Postoperative MRI confirmed complete excision of both the lesions. The child reported regression of precocious puberty and remained seizure-free until the last follow-up 6 months after surgery. A hypothesis based on a dysontogenetic mechanism is discussed to explain the unusual occurrence of the dual, seemingly unrelated pathologies. Hemorrhage into the hamartoma was an added oddity in this case. PMID- 22777075 TI - Cellular basis for the olfactory response to nicotine. AB - Smokers regulate their smoking behavior on the basis of sensory stimuli independently of the pharmacological effects of nicotine (Rose J. E., et al. (1993) Pharmacol., Biochem. Behav.44 (4), 891-900). A better understanding of sensory mechanisms underlying smoking behavior may help to develop more effective smoking alternatives. Olfactory stimulation by nicotine makes up a considerable part of the flavor of tobacco smoke, yet our understanding of the cellular mechanisms responsible for olfactory detection of nicotine remains incomplete. We used biophysical methods to characterize the nicotine sensitivity and response mechanisms of neurons from olfactory epithelium. In view of substantial differences in the olfactory receptor repertoire between rodent and human (Mombaerts P. (1999) Annu. Rev. Neurosci.22, 487-509), we studied biopsied human olfactory sensory neurons (OSNs), cultured human olfactory cells (Gomez G., et al. (2000) J. Neurosci. Res.62 (5), 737-749), and rat olfactory neurons. Rat and human OSNs responded to S(-)-nicotine with a concentration dependent influx of calcium and activation of adenylate cyclase. Some rat OSNs displayed some stereoselectivity, with neurons responding to either enantiomer alone or to both. Freshly biopsied and primary cultured human olfactory neurons were less stereoselective. Nicotinic cholinergic antagonists had no effect on the responses of rat or human OSNs to nicotine. Patch clamp recording of rat OSNs revealed a nicotine-activated, calcium-sensitive nonspecific cation channel. These results indicate that nicotine activates a canonical olfactory receptor pathway rather than nicotinic cholinergic receptors on OSNs. Further, because the nicotine sensitive mechanisms of rodents appear generally similar to those of humans, this animal model is an appropriate one for studies of nicotine sensation. PMID- 22777077 TI - Effects of a perfusion bioreactor activated novel bone substitute in spine fusion in sheep. AB - PURPOSE: To evaluate the effect of a large perfusion-bioreactor cell-activated bone substitute, on a two-level large posterolateral spine fusion sheep model. METHODS: A 50 mm long porous biphasic-calcium-phosphate bone substitute reinforced with poly(D,L-lactide) and, activated with bone marrow derived mononuclear-cells (BMNC) was used. Eighteen sheep were divided into two groups and one group (n = 9) had BMNC-activated bone substitutes and cell-free substitutes implanted. The second group (n = 9) had autograft supplemented with BMNC and regular autograft implanted. The implant material was alternated between spine level L2-L3 and L4-L5 in both groups. MicroCT was used to compare the spine fusion efficacy and bone structure of the two groups as well as the implanted bone substitutes and non-implanted substitutes. RESULTS: After 41/2 months six sheep survived in both groups and we found five spine levels were fused when using activated bone substitute compared to three levels with cell-free bone substitute (p = 0.25). Five sheep fused at both levels in the autograft group. A significant increased bone density (p < 0.05) and anisotropy (p < 0.05) was found in the group of activated bone substitutes compared to cell-free bone substitute and no difference existed on the other parameters. The implanted bone substitutes had a significant higher bone density and trabecular thickness than non-implanted bone substitutes, thus indicating that the PLA reinforced BCP had osteoconductive properties (p < 0.05). No effect of the supplemented BMNC to autograft was observed. The autograft group had a significant higher bone density, trabecular thickness and degree of anisotropy than the implanted bone substitutes (p < 0.05), but a lower connectivity density existed (p < 0.05). This indicates that though the activated substitute might have a similar fusion efficacy to autograft, the fusion bridge is not of equal substance. CONCLUSION: We found that bioreactor-generated cell-based bone substitutes seemed superior in fusion ability when compared to cell-free bone substitute and comparable to autograft in fusion ability, but not in bone structure. This combined with the favorable biocompatible abilities and strength comparable to human cancellous bone indicates that it might be a suitable bone substitute in spine fusion procedures. PMID- 22777079 TI - Can we better identify thin cutaneous melanomas that are likely to metastasize and cause death? PMID- 22777080 TI - Hypothermia, hypotension, hypersomnia, and obesity associated with hypothalamic lesions in a patient positive for the anti-aquaporin 4 antibody: a case report and literature review. AB - OBJECTIVE: To describe a patient positive for the anti-aquaporin 4 antibody with hypothalamic lesions showing hypothermia, hypotension, hypersomnia, and obesity. DESIGN: Case report. SETTING: University hospital. PATIENT: We describe a 21-year old woman who was positive for anti-aquaporin 4 antibody and presented with hypothermia, hypotension, and hypersomnia owing to bilateral hypothalamic lesions as the only abnormal clinical finding. RESULTS: Immediate steroid administration resulted in significant improvement of the patient's vital signs and imaging findings; however, her cognitive impairment and sleepiness persisted, and she subsequently developed obesity. Decreased cerebrospinal fluid orexin levels and sleep studies confirmed the diagnosis of narcolepsy due to medical condition. Physicians should be aware that neuromyelitis optica spectrum disorders can initially involve the hypothalamus. CONCLUSIONS: We emphasize that measurement of anti-aquaporin 4 antibody is of clinical importance in the differential diagnosis of hypothalamic lesions. PMID- 22777081 TI - Oral ibuprofen for treatment of patent ductus arteriosus: more than a cheap alternative? PMID- 22777082 TI - Estimation of factors from natural and anthropogenic radioactivity present in the surface soil and comparison with DCF values. AB - A study was conducted to evaluate the absorbed rate coefficient of (238)U, (232)Th, (40)K and (137)Cs present in soil. A total of 31 soil samples and the corresponding terrestrial dose rates at 1 m from different locations were taken around the Anushaktinagar region, where the litho-logy is dominated by red soil. A linear regression model was developed for the estimation of these factors. The estimated coefficients (nGy h(-1) Bq(-1) kg(-1)) were 0.454, 0.586, 0.035 and 0.392, respectively. The factors calculated were in good agreement with the literature values. PMID- 22777083 TI - Epidemiology: subclinical hypothyroidism and mortality. PMID- 22777084 TI - Neuroendocrine correlates of childhood trauma in CFS. PMID- 22777085 TI - Diagnosis: test spots low-risk thyroid nodules. PMID- 22777078 TI - Confirmatory factor analysis of the ADNI Neuropsychological Battery. AB - The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a large multi-center study designed to develop optimized methods for acquiring longitudinal neuroimaging, cognitive, and biomarker measures of AD progression in a large cohort of patients with Alzheimer's disease (AD), patients with Mild Cognitive Impairment, and healthy controls. Detailed neuropsychological testing was conducted on all participants. We examined the factor structure of the ADNI Neuropsychological Battery across older adults with differing levels of clinical AD severity based on the Clinical Dementia Rating Scale (CDR). Confirmatory factor analysis (CFA) of 23 variables from 10 neuropsychological tests resulted in five factors (memory, language, visuospatial functioning, attention, and executive function/processing speed) that were invariant across levels of cognitive impairment. Thus, these five factors can be used as indicators of cognitive function in older adults who are participants in ADNI. PMID- 22777087 TI - Some novel molecular frameworks involving representative elements. AB - Several new molecular frameworks with interesting structures, based on clusters of main group elements have been studied at different levels of theory with various basis sets. Conceptual density functional theory based reactivity descriptors and nucleus independent chemical shift provide important insights into their bonding, reactivity, stability and aromaticity. PMID- 22777088 TI - Risk of perinatal death in early-onset intrauterine growth restriction according to gestational age and cardiovascular Doppler indices: a multicenter study. AB - OBJECTIVE: To assess the value of gestational age and cardiovascular Doppler indices in predicting perinatal mortality in a multicenter cohort of early-onset intrauterine growth-restricted (IUGR) fetuses. METHODS: A multicenter prospective cohort study including 157 early-onset (<34 weeks) IUGR cases with abnormal umbilical artery (UA) Doppler was conducted. Cardiovascular assessment included the ductus venosus (DV), the aortic isthmus flow index (IFI), and the myocardial performance index (MPI). Isolated and combined values to predict the risk of perinatal death were evaluated by logistic regression and by decision tree analysis, where the gestational age at delivery, UA, and middle cerebral artery (MCA) were also included as covariates. RESULTS: Perinatal mortality was 17% (27/157). All parameters were significantly associated with perinatal death, with individual odds ratios (OR) of 25.2 for gestational age below 28 weeks, 12.1 for absent/reversed DV atrial flow, 5.3 for MCA pulsatility index <5th centile, 4.6 for UA absent/reversed diastolic end-flow, 1.8 for IFI <5th centile, and 1.6 for MPI >95th centile. Decision tree analysis identified gestational age at birth as the best predictor of death (<26 weeks, 93% mortality; 26-28 weeks, 29% mortality, and >28 weeks, 3% mortality). Between 26 and 28 weeks, DV atrial flow allowed further stratification between high (60%) and low risk (18%) of mortality. CONCLUSIONS: Gestational age largely determines the risk of perinatal mortality in early-onset IUGR before 26 weeks and later than 28 weeks of gestation. The DV may improve clinical management by stratifying the probability of death between 26 and 28 weeks of gestation. PMID- 22777089 TI - Cycloisomerization of dienes and enynes catalysed by a modified ruthenium carbene species. AB - Cycloisomerization is a totally atom economic procedure which converts dienes and enynes into cyclic molecules. Modification of Grubbs' 2nd generation catalysts by reaction with dimethylformamide provides a new species able to catalyse this transformation. Selection of suitable conditions allowed high yields and selectivity. Studies performed in order to identify the catalytic species point to a non-carbenic ruthenium complex that has lost the phosphine. No hydride signals appeared. In addition, the reaction works with enynes and the new species catalyses efficiently crossed cyclotrimerizations of alkynes with diynes. PMID- 22777091 TI - Accelerated vaccine development against emerging infectious diseases. AB - Emerging and re-emerging infectious diseases represent a major challenge to vaccine development since it involves two seemingly contradictory requirements. Rapid and flexible vaccine generation while using technologies and processes that can facilitate accelerated regulatory review. Development in the "-omics" in combination with advances in vaccinology offer novel opportunities to meet these requirements. Here we describe how a consortium of five different organizations from academia and industry is addressing these challenges. This novel approach has the potential to become the new standard in vaccine development allowing timely deployment to avert potential pandemics. PMID- 22777090 TI - A vaccinia virus renaissance: new vaccine and immunotherapeutic uses after smallpox eradication. AB - In 1796, Edward Jenner introduced the concept of vaccination with cowpox virus, an Orthopoxvirus within the family Poxviridae that elicits cross protective immunity against related orthopoxviruses, including smallpox virus (variola virus). Over time, vaccinia virus (VACV) replaced cowpox virus as the smallpox vaccine, and vaccination efforts eventually led to the successful global eradication of smallpox in 1979. VACV has many characteristics that make it an excellent vaccine and that were crucial for the successful eradication of smallpox, including (1) its exceptional thermal stability (a very important but uncommon characteristic in live vaccines), (2) its ability to elicit strong humoral and cell-mediated immune responses, (3) the fact that it is easy to propagate, and (4) that it is not oncogenic, given that VACV replication occurs exclusively within the host cell cytoplasm and there is no evidence that the viral genome integrates into the host genome. Since the eradication of smallpox, VACV has experienced a renaissance of interest as a viral vector for the development of recombinant vaccines, immunotherapies, and oncolytic therapies, as well as the development of next-generation smallpox vaccines. This revival is mainly due to the successful use and extensive characterization of VACV as a vaccine during the smallpox eradication campaign, along with the ability to genetically manipulate its large dsDNA genome while retaining infectivity and immunogenicity, its wide mammalian host range, and its natural tropism for tumor cells that allows its use as an oncolytic vector. This review provides an overview of new uses of VACV that are currently being explored for the development of vaccines, immunotherapeutics, and oncolytic virotherapies. PMID- 22777092 TI - Further progress on defining highly conserved immunogenic epitopes for a global HIV vaccine: HLA-A3-restricted GAIA vaccine epitopes. AB - Two major obstacles confronting HIV vaccine design have been the extensive viral diversity of HIV-1 globally and viral evolution driven by escape from CD8(+) cytotoxic T-cell lymphocyte (CTL)-mediated immune pressure. Regions of the viral genome that are not able to escape immune response and that are conserved in sequence and across time may represent the "Achilles' heel" of HIV and would be excellent candidates for vaccine development. In this study, T-cell epitopes were selected using immunoinformatics tools, combining HLA-A3 binding predictions with relative sequence conservation in the context of global HIV evolution. Twenty seven HLA-A3 epitopes were chosen from an analysis performed in 2003 on 10,803 HIV-1 sequences, and additional sequences were selected in 2009 based on an expanded set of 43,822 sequences. These epitopes were tested in vitro for HLA binding and for immunogenicity with PBMCs of HIV-infected donors from Providence, Rhode Island. Validation of these HLA-A3 epitopes conserved across time, clades, and geography supports the hypothesis that epitopes such as these would be candidates for inclusion in our globally relevant GAIA HIV vaccine constructs. PMID- 22777093 TI - In vitro assessment of the allergenicity of novel MF59-adjuvanted pandemic H1N1 influenza vaccine produced in dog kidney cells. AB - A licensed inactivated MF59-adjuvanted seasonal influenza vaccine (Optaflu) produced in canine kidney cells (MDCK 33016-PF) contained no egg proteins and did not trigger degranulation in rat basophilic leukemia (RBL) cells passively sensitized with human anti-dog IgE, supporting its safe use in dog-allergic individuals. The cell-derived pandemic H1N1 influenza vaccine was also adjuvanted with the emulsion adjuvant MF59, and support for its similar safe use was sought. We sought to evaluate in vitro allergenicity of the MF59-adjuvanted cell-derived pandemic H1N1 influenza vaccine in subjects with dog allergy, with a mediator release assay. RBL-2H3 cells transfected with human Fcepsilon receptor type 1 were sensitized with sera from adult dog-allergic subjects and stimulated with serial dilutions of pandemic H1N1 influenza vaccine and dog dander extract. beta N-hexosaminidase release (NHR) was used as a marker of RBL degranulation.. Median dog dander-specific IgE in 30 dog-allergic subjects was 27.7 kU(A)/L (range 10.1; > 100); and in 5 dog non-allergic subjects was < 0.35 kU(A)/L (UniCAP system). Median (range) maximum NHR in dog-allergic subjects was: pandemic H1N1 influenza vaccine 1.1% (0; 4.4) and dog dander 6.9% (0.7; 37.3), P < 0.001. In conclusion, MF59-adjuvanted pandemic H1N1 influenza vaccine produced in continuous canine kidney cells did not trigger degranulation in RBL cells passively sensitized with human anti-dog IgE, supporting its safe use in dog-allergic individuals. PMID- 22777094 TI - Homologous and heterologous antibody responses to a one-year booster dose of an MF59((r)) adjuvanted A/H5N1 pre-pandemic influenza vaccine in pediatric subjects. AB - BACKGROUND: Primary immunization with two doses of MF59 ((r)) -adjuvanted A/H5N1 influenza vaccine has been shown to be highly immunogenic and well tolerated in children and adolescents. Assessment of long-term antibody persistence after priming, and the effects of a one-year booster dose in children and adolescents was needed. OBJECTIVES: This study assessed homologous and heterologous antibody responses to a one-year booster dose of MF59-adjuvanted A/H5N1 influenza vaccine in previously primed children. RESULTS: Twelve months after primary vaccination, persistent, homologous, seroprotective HI antibody titers (>= 40) were observed in 46%, 26% and 30% of toddlers, children and adolescents; following booster vaccination, seroprotection rates increased to 99%, 98% and 91%, respectively. All toddlers and children, and 99% of adolescents achieved MN antibody titers >= 40. Cross-reactive A/H5N1 antibodies were detected in 94-98% of subjects after booster vaccination. SUBJECTS AND METHODS: Twelve months after primary vaccination, toddlers, children and adolescents received a single booster dose of the same A/H5N1 vaccine. Paired sera were collected before and three weeks after booster vaccination. Homologous antibody responses against the A/Vietnam/1194/2004 vaccine strain were measured by hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization (MN) assays. Heterologous antibody responses against A/Indonesia/5/2005 and A/Anhui/1/2005 strains were assessed by MN assay only. CONCLUSIONS: Two priming doses of MF59 adjuvanted A/H5N1 vaccine resulted in homologous and heterologous antibody responses which persisted for up to one year after immunization. A one-year booster dose was highly immunogenic, generating high homologous and cross reactive A/H5N1 antibody titers. PMID- 22777095 TI - The prevalence and genotype of human papillomavirus on cervical samples from an Irish female population with external genital warts. AB - The aim of this study was to determine the cervical genotype profile of females who presented to an STI Clinic with external genital warts (EGW); and to determine the potential vaccine coverage prior to the uptake of the HPV vaccines. Sixty-one cervical scrapings were taken from females aged 18-35 y who had external genital warts or a history of external genital warts. The resulting 50 samples that were positive for HPV-DNA were subjected to genotype identification. Forty-six of these samples had detectable genotypes by LIPA analysis and most (78%, 36/46) had multiple low risk (LR) and high risk (HR) genotypes on the cervix. Twenty-five of these samples (54%) had more than 1 HR genotype. Of the 36 patients who had any HR genotypes, 18 (50%) were identified to have the most oncogenic HPV genotypes, namely 16 and 18. Three of these samples had both 16 and 18 on the cervix. The presence of multiple HR genotypes on the majority of cervical samples from a self-referred population of females with EGW is presented. This study is of importance since persistent HR-HPV is the necessary risk factor in the development of precancerous and cancerous lesions of the cervix. Gardisil, the quadrivalent HPV vaccine would have been useful in the prevention of 28% (13/46) of these infections. PMID- 22777096 TI - Single-dose, live-attenuated Japanese encephalitis vaccine in children aged 12-18 months: randomized, controlled phase 3 immunogenicity and safety trial. AB - This trial in 1200 JE-vaccination naive children (age 12-18 mo) in Thailand and the Philippines aimed to demonstrate consistency of three successive industrial scale manufacturing lots of live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) and consistency between industrial scale manufacturing lots and a fourth, development lot. Children received JE-CV from one of three successive industrial scale lots produced in Thailand (n = 899), or from a fourth development lot produced in the USA (n = 199), or hepatitis A control vaccine (n = 102). Antibodies were assessed by 50% plaque reduction neutralization test (PRNT(50)) at screening and Day 28. Seroconversion rates (titer of < 10 at baseline and >= 10 on Day 28, or a four-fold rise from a baseline titer of >= 10) were determined per group. Lot-to-lot consistency of seroconversion rate and GMT was demonstrated between the 3 industrial scale lots, and between these lots and the US lot. Seroconversion rate on pooled data 28 d after JE-CV vaccination (Thai lots) was 95.0% [95% confidence interval (CI); 93.3-96.3]. The safety profile of JE-CV was favorable and comparable with hepatitis A vaccine. There were no serious adverse events related to vaccination. This study demonstrated the consistency of three successive industrial scale JE-CV vaccine lots, as well as consistency with a development lot. The study also demonstrated that a single dose of JE-CV is well tolerated and elicits a high protective immune response, seroconverting 95% of JE-naive Asian children aged 12-18 mo. PMID- 22777097 TI - Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers. AB - This study assessed antibody persistence and immune memory to hepatitis B vaccine 20 y after priming with a recombinant hepatitis B virus (HBV) vaccine during infancy. Infants were vaccinated according to a 0, 1, 6 mo schedule with or without simultaneous administration of hepatitis B immunoglobulin (HBIg). Half of the subjects enrolled received an interim booster dose at year 5 (boosted) group, whereas the other half of the subjects enrolled did not (unboosted group). Antibody persistence was assessed until year 20. Immune memory was assessed by administration of a final HBV vaccine challenge dose at year 20 in a second study. At year 20, anti-HBs antibody concentration >= 10 mIU/ml rates and GMCs were higher among subjects in the boosted group (84.2% [16/19]; 95%CI: 60.4-96.6) when compared with those in the unboosted group [44.0% (11/25)]; 95% CI: 24.4 65.1). After the HBV vaccine challenge dose at year 20, anti-HBs anamnestic response for subjects in the unboosted and boosted groups was observed in 93.1% (95% CI: 77.2-99.2) and 100% (95% CI: 76.8-100) of subjects, respectively. The mean anti-HBs antibody concentration (GMC) was 562.0 mIU/ml (292.5-1079.7 mIU/ml) post administration of the challenge dose; this is a 28.5 fold increase from the pre- to post-challenge dose administration at year 20. This study demonstrates persistence of anti-HBs antibodies and presence of immune memory following hepatitis B vaccination for up to at least 20 y in Thailand. Immune memory was demonstrated for virtually all subjects, regardless whether they received they had received the additional HBV dose or not. The challenge dose at year 20 was well tolerated and a robust response was demonstrated. ClinicalTrials.gov Identifier: NCT00240526, NCT00774995. PMID- 22777098 TI - Extended coverage of HPV vaccination in middle-aged adults to prevent oropharyngeal cancers. PMID- 22777100 TI - Report from the field: Fifth Vaccine Renaissance in Providence RI. AB - When the next pandemic emerges, will we be ready? Experts say that the number of animal to human "species jumps" is bound to increase as populations increase and the speed of travel between continents accelerates. Typical pandemic timelines no longer apply.(1) Pandemic H1N1 traveled the world in just weeks, as did SARS, despite major efforts to contain both outbreaks. The danger of emerging infectious disease to global health is compounded by the potential threat for malevolent bioengineering of existing pathogens and their deliberate dissemination.(2) PMID- 22777099 TI - Effectiveness and harms of seasonal and pandemic influenza vaccines in children, adults and elderly: a critical review and re-analysis of 15 meta-analyses. AB - Fifteen meta-analyses have been published between 1995 and 2011 to evaluate the efficacy/effectiveness and harms of diverse influenza vaccines--seasonal, H5N1 and 2009 (H1N1)--in various age-classes (healthy children, adults or elderly). These meta-analyses have often adopted different analyses and study selection criteria. Because it is difficult to have a clear picture of vaccine benefits and harms examining single systematic reviews, we compiled the main findings and evaluated which could be the most reasonable explanations for some differences in findings (or their interpretation) across previously published meta-analyses. For each age group, we performed analyses that included all trials that had been included in at least one relevant meta-analysis, also exploring whether effect sizes changed over time. Although we identified several discrepancies among the meta-analyses on seasonal vaccines for children and elderly, overall most seasonal influenza vaccines showed statistically significant efficacy/effectiveness, which was acceptable or high for laboratory-confirmed cases and of modest magnitude for clinically-confirmed cases. The available evidence on parenteral inactivated vaccines for children aged < 2 y remains scarce. Pre-pandemic "avian" H5N1 and pandemic 2009 (H1N1) vaccines can achieve satisfactory immunogenicity, but no meta-analysis has addressed H1N1 vaccination impact on clinical outcomes. Data on harms are overall reassuring, but their value is diminished by inconsistent reporting. PMID- 22777101 TI - Concurrent adaptation to four different visual rotations. AB - The human sensorimotor system can concurrently adapt to two different distortions without interference when the distortions are cued by different contexts. We investigated whether this holds with four distortions as well. Subjects were exposed to an interlaced sequence of +30 degrees , -30 degrees , +60 degrees , and -60 degrees visuomotor rotations as the adaptation phase, cued by combinations of workspace location and by the arm used. Adaptation phase was followed by two episodes in each condition without any distortion testing the aftereffects. Results showed that the error at the onset of adaptation gradually decreased during adaptation to all four distortions without any sign of interference between the conditions. Furthermore, aftereffects of adaptation to +/-30 degrees rotation were significantly greater than of adaptation to +/-60 degrees rotation. We conclude that the human sensorimotor system is able to concurrently adapt to four different visual distortions when they are cued by different contexts. However, the results of aftereffects are ambiguous: Recalibration could be based on at least four parallel modules. PMID- 22777104 TI - Changes in angiotensin II type 1 receptor expression in the rat bladder by bladder outlet obstruction. AB - PURPOSE: To demonstrate the change in the expression of angiotensin II type 1 receptor (AT1) in the rat bladder with partial bladder outlet obstruction (P BOO). MATERIALS AND METHODS: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups, a P-BOO group and a control group. The rats of the P-BOO group were divided into six groups: a sham-operated control group, 1 day postoperatively, 2 days postoperatively, 4 days postoperatively, 7 days postoperatively and 14 days postoperatively. The cystometric findings and immunohistochemical staining of the detrusor muscle with the AT1 antibody were compared in each group. RESULTS: AT1 localized on the cell membrane of the detrusor smooth muscle and in cytoplasm of suburothelial myofibroblasts in the control rats. The expression of AT1 disappeared in the detrusor muscle and suburothelial myofibroblasts in P-BOO, but AT1 was highly expressed in urothelial cells 1 day after surgery. The expression of AT1 in urothelial cells gradually decreased with time after surgery. AT1 completely disappeared in urothelial cells 14 days after surgery. CONCLUSIONS: The present study demonstrated that the site of AT1 expression changes in response to the mechanical stress caused by P-BOO, and finally there was no expression of AT1 in rat bladder tissue following P-BOO. These data suggest the change in AT1 expression may play a role in bladder function. PMID- 22777103 TI - Training-induced modifications of corticospinal reactivity in severely affected stroke survivors. AB - When permitted access to the appropriate forms of rehabilitation, many severely affected stroke survivors demonstrate a capacity for upper limb functional recovery well in excess of that formerly considered possible. Yet, the mechanisms through which improvements in arm function occur in such profoundly impaired individuals remain poorly understood. An exploratory study was undertaken to investigate the capacity for brain plasticity and functional adaptation, in response to 12-h training of reaching using the SMART Arm device, in a group of severely affected stroke survivors with chronic upper limb paresis. Twenty-eight stroke survivors were enroled. Eleven healthy adults provided normative data. To assess the integrity of ipsilateral and contralateral corticospinal pathways, transcranial magnetic stimulation was applied to evoke responses in triceps brachii during an elbow extension task. When present, contralateral motor-evoked potentials (MEPs) were delayed and reduced in amplitude compared to those obtained in healthy adults. Following training, contralateral responses were more prevalent and their average onset latency was reduced. There were no reliable changes in ipsilateral MEPs. Stroke survivors who exhibited contralateral MEPs prior to training achieved higher levels of arm function and exhibited greater improvements in performance than those who did not initially exhibit contralateral responses. Furthermore, decreases in the onset latency of contralateral MEPs were positively related to improvements in arm function. Our findings demonstrate that when severely impaired stroke survivors are provided with an appropriate rehabilitation modality, modifications of corticospinal reactivity occur in association with sustained improvements in upper limb function. PMID- 22777102 TI - Specialization of reach function in human posterior parietal cortex. AB - Posterior parietal cortex (PPC) plays an important role in the planning and control of goal-directed action. Single-unit studies in monkeys have identified reach-specific areas in the PPC, but the degree of effector and computational specificity for reach in the corresponding human regions is still under debate. Here, we review converging evidence spanning functional neuroimaging, parietal patient and transcranial magnetic stimulation studies in humans that suggests a functional topography for reach within human PPC. We contrast reach to saccade and grasp regions to distinguish functional specificity and also to understand how these different goal-directed actions might be coordinated at the cortical level. First, we present the current evidence for reach specificity in distinct modules in PPC, namely superior parietal occipital cortex, midposterior intraparietal cortex and angular gyrus, compared to saccade and grasp. Second, we review the evidence for hemispheric lateralization (both for hand and visual hemifield) in these reach representations. Third, we review evidence for computational reach specificity in these regions and finally propose a functional framework for these human PPC reach modules that includes (1) a distinction between the encoding of reach goals in posterior-medial PPC as opposed to reach movement vectors in more anterior-lateral PPC regions, and (2) their integration within a broader cortical framework for reach, grasp and eye-hand coordination. These findings represent both a confirmation and extension of findings that were previously reported for the monkey. PMID- 22777106 TI - Polymorphisms in the vitamin D receptor gene and parathyroid hormone gene in the development and progression of diabetes mellitus and its chronic complications, diabetic nephropathy and non-diabetic renal disease. AB - BACKGROUND: We chose to study polymorphisms of vitamin D receptor gene (VDR) and parathyroid hormone genes (PTH), whose protein products significantly affect calciumphosphate metabolism in kidneys and are implicated in the pathogenesis of diabetes, which may also involve kidney damage. METHODS: Distribution of genotypes of four polymorphisms in VDR gene, i.e, TaqI (rs731236), BsmI (rs1544410) ApaI (rs7975232), FokI (rs2228570) and two polymorphisms of PTH gene, i.e., DraII (rs6256), BstBI (rs6264), were studied using PCRRFLP. Examined groups consisted of 147 patients with diabetes (DM), 47 patients with nondiabetic renal disease (NDRD), 132 patients with diabetic nephropathy (DN) and 118 healthy subjects. CONCLUSION: Comparison of DN group and healthy subjects identified statistically significant difference for the FokI polymorphism in VDR gene (P<10 4) and also for the BstBI polymorphism in PTH gene (P=0,023). Differences in DraII polymorphism distribution in PTH gene were statistically significant in each group of patients compared to healthy subjects. In DN patients, the BBFFAATt combination of VDR gene was more frequent than in healthy subjects (P=0,046), and the BbFFAaTt variant was more frequent than in DM2 patients (P=0,018). The BBDD haplotype of PTH gene seems to be a predisposing factor for diabetes itself (P=0,019). PMID- 22777105 TI - Is infertility associated with childhood autism? AB - Concerns persist about a possible link between infertility and risk of autism spectrum disorders (ASD). Interpretation of existing studies is limited by racial/ethnic homogeneity of study populations and other factors. Using a case control design, we evaluated infertility history and treatment documented in medical records of members of Kaiser Permanente Northern California. Among singletons (349 cases, 1,847 controls), we found no evidence to support an increase in risk of ASD associated with infertility. Among multiple births (21 cases, 54 controls), we found an increased risk associated with infertility history and with infertility evaluations and treatment around the time of index pregnancy conception; however, small sample size and lack of detailed data on treatments preclude firm interpretation of results for multiple births. PMID- 22777109 TI - Effect of the cellular-type artificial oxygen carrier hemoglobin vesicle as a resuscitative fluid for prehospital treatment: experiments in a rat uncontrolled hemorrhagic shock model. AB - The hemoglobin vesicle (Hb-vesicle) is a cellular-type artificial oxygen carrier showing a resuscitative effect comparable to that of blood transfusion in several animal models. However, the efficacy of Hb-vesicles for resuscitation when the hemorrhage cannot be controlled remains unclear. Therefore, we used Hb-vesicles in a rat hemorrhagic shock model caused by continuous bleeding. For inducing uncontrolled hemorrhage, animals were heparinized and bled from the caudal artery. Fluid resuscitation was subsequently performed with five materials: Hb vesicle suspension in a 5% albumin (Alb) solution (HbV), washed red blood cells (wRBC) in a 6% hydroxyethyl starch (HES) solution, 5% Alb, 6% HES, and saline (Sal). During the experiment, all animals in the HbV and wRBC groups survived, whereas all those in the Alb and HES groups died. In the Sal group, five of seven animals died. In the HbV and wRBC groups, the heart rate, mean arterial pressure, and blood lactic acid levels were stabilized during resuscitation. Meanwhile, the hematocrit levels of the HbV, Alb, and HES groups showed sharp decreases (HbV: 6.8% +/- 1.7%, Alb: 6.8% +/- 0.8%, HES: 5.5% +/- 0.7% at 100% total circulated blood volume; final hematocrit of the HbV group: 1.5% +/- 0.5%). These results suggest that shocked animals can survive longer when the Hb-vesicle supply is maintained and that HbV showed a similar effect to wRBC in maintaining the circulating volume and oxygen metabolism. Continuous infusion of Hb-vesicles may extend the survival of trauma victims with uncontrolled hemorrhage until they have reached a trauma center. PMID- 22777108 TI - Tea consumption is inversely associated with weight status and other markers for metabolic syndrome in US adults. AB - PURPOSE: Tea (Camellia sinensis) is a widely consumed beverage, and laboratory and some intervention studies have indicated the potential health benefits of hot tea. The present study examines the association between tea consumption (evaluating hot and iced tea independently) and markers for metabolic syndrome adults in a sample of 6,472 who participated in the 2003-2006 National Health and Nutrition Examination surveys. METHODS: Tea consumption was evaluated using food frequency questionnaires and 24-h dietary recalls. Seventy percent of the sample reported any consumption of iced tea and 16 % were daily consumers, whereas approximately 56 % of this sample reported hot tea consumption and 9 % were daily consumers. RESULTS: Hot tea consumption was inversely associated with obesity: tea consumers had lower mean waist circumference and lower BMI (25 vs. 28 kg/m2 in men; 26 vs. 29 kg/m2 in women; both P < 0.01) than non-consumers after controlling for age, physical activity, total energy intake, and other confounders. For iced tea consumption, the association was reversed: increased iced tea consumption was associated with higher BMI, greater waist circumference, and greater subcutaneous skinfold thickness after controlling for age, physical activity, energy intake, sugar intake, and other confounders. Hot tea consumption was associated with beneficial biomarkers of cardiovascular disease risk and inflammation (increased high-density lipoprotein-associated cholesterol and decreased C-reactive protein in both sexes, and reduced triglycerides in women), whereas the association with iced tea consumption was again reversed. CONCLUSIONS: These cross-sectional results support growing laboratory data, which demonstrate the negative association of hot tea intake with markers of MetS. PMID- 22777107 TI - Fate of dietary phytosteryl/-stanyl esters: analysis of individual intact esters in human feces. AB - PURPOSE: The objective was to investigate the metabolic fate of phytosteryl/ stanyl fatty acid and ferulic acid esters upon consumption by healthy humans. METHODS: A capillary gas chromatographic methodology was employed to follow a randomized, single-blind three group crossover clinical trial and to quantify simultaneously individual intact esters, liberated phytosterols/-stanols and their metabolites in feces. Skimmed milk drinking yogurts enriched with complex mixtures of phytosteryl/-stanyl fatty acid esters and ferulates, respectively, were employed as food carriers. RESULTS: On average, 73 % of total plant stanyl fatty acid esters and 80 % of total plant steryl fatty acid esters were hydrolyzed. Among the individuals, the hydrolysis rates ranged from 40 to 96 %. In addition, there were subject-dependent discrepancies between the amounts of phytosterols/-stanols actually determined in the feces and the calculated hydrolysis rates. On average, 69 % of the amounts of sterols/stanols expected from the amounts of remaining intact esters were found. CONCLUSIONS: The study revealed large interindividual variability regarding the recoveries of dietary phytosteryl/-stanyl esters upon gastrointestinal passage in healthy humans. Nevertheless, there was a significant impact of the acid moiety (oleate=linoleate=linolenate>eicosanoate>palmitate>ferulate) on the hydrolysis rates; the influence of the phytosterol/-stanol moiety was less pronounced. PMID- 22777110 TI - Resuscitation fluids and endotoxin-induced myocardial dysfunction: is selection a load-independent differential issue? AB - Along with redistributive shock, myocardial dysfunction is now recognized as highly prevalent in early severe sepsis. Indeed, aside from their distinct loading potency, resuscitation fluids have been poorly investigated as to their specific molecular impact on myocardial dysfunction. The objective of this study was to evaluate the load-independent biological impact of different resuscitation fluids on endotoxin-induced myocardial dysfunction. Adult rats implanted with a central venous catheter were given an intraperitoneal injection of endotoxin (lipopolysaccharides [LPSs], Escherichia coli, 10 mg/kg) or normal saline (sham) and subsequently infused or not with similar "fluid potency" loading resuscitation fluid (normal saline, albumin [Alb], or hypertonic saline solution) for 6 to 24 h, followed by echocardiographic and hemodynamic monitoring together with biochemical and histopathologic evaluation. Intervention was to assess the selective influence of load-independent fluid infusion on the aforementioned parameters in groups of animals challenged or not with LPS. At comparative plasma volumes, Alb improved myocardial homeostasis after LPS challenge by (i) reducing left ventricular relative wall diastolic thickness, interstitial space enlargement, and endogenous Alb content; (ii) limiting cardiac apoptosis and sustaining extracellular signal-regulated mitogen-activated protein kinase activation; and (iii) enhancing the expression pattern of heme-oxygenase 1/inducible nitric oxide synthase. Hypertonic saline solution was also cardioprotective by early prevention of myocardial dysfunction and by reducing cardiac apoptosis. Fluid infusions have distinct load-independent structural/biological impacts on endotoxin-induced myocardial dysfunction. Albumin and hypertonic saline solution are the most pleiotropic fluids in protecting the heart after a "sepsis" hit. PMID- 22777111 TI - Bacterial sensing, cell signaling, and modulation of the immune response during sepsis. AB - Since the definition of systemic inflammatory response syndrome/sepsis was originally proposed, a large amount of new information has been generated showing a much more complex scenario of inflammatory and counterinflammatory responses during sepsis. Moreover, some fundamental mechanisms of sensing and destroying invading microorganisms have been uncovered, which include the discovery of TLR4 as the lipopolysaccharide (LPS) gene, implications of innate immune cells as drivers of the adaptive response to infection, and the modulation of multiple accessory molecules that stimulate or inhibit monocyte/macrophage and lymphocyte interactions. The complexity of the infection/injury-induced immune response could be better appreciated with the application of genomics and proteomics studies, and LPS was a useful tool in many of these studies. In this review, we discuss aspects of bacterial recognition and induced cellular activation during sepsis. Because of the relevance of endotoxin (LPS) research in the field, we focus on LPS and host interactions as a clue to understand microorganisms sensing and cell signaling, then we discuss how this response is modulated in septic patients. PMID- 22777112 TI - Lung endothelial cell apoptosis during ischemic acute kidney injury. AB - Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that drive lung inflammatory cascades, tumor necrosis factor receptor 1 (TNFR1) mediated programmed cell death, and microvascular barrier dysfunction, leading to acute lung injury. We hypothesized that lung microvascular endothelial cells (ECs), with their integral role in maintaining the lung-semipermeable barrier, were key cellular targets of TNFR1-mediated apoptosis during ischemic AKI. Male C57/BL6 mice and Sprague-Dawley rats underwent 60 min of bilateral renal pedicle occlusion (IRI) or sham laparotomy (sham) and were killed at 4 or 24 h. Colocalization with TUNEL, DAPI, and CD34 was performed to identify EC-specific apoptosis. Mouse ECs (CD45/CD31) isolated with novel tissue digestion techniques and magnetic microbead sorting underwent quantitative real-time polymerase chain reaction SuperArray analysis with 84 apoptosis-related genes. In parallel, rat lung microvascular ECs grown to confluence were treated with serum from rats obtained following sham or kidney IRI. Rat lung microvascular ECs treated +/- etanercept, a TNF-alpha/TNFR1 signaling inhibitor, underwent custom real-time polymerase chain reaction analysis for proapoptotic and TNF superfamily transcriptional events, and apoptosis was identified with caspase 3 and poly(ADP ribose) polymerase activity assays. In vivo, TUNEL-positive cells colocalized with CD34 in whole-lung tissue and isolated lung ECs demonstrated a proapoptotic transcriptome during ischemic AKI. In vitro, ischemic AKI incited proapoptotic (FasL, Dapk1, Bcl10) and TNF superfamily (TNFR1, TNFR2, TNF-alpha) gene activation and increased caspase 3 and poly(ADP-ribose) polymerase activity at 24 h versus sham. Compared with vehicle, treatment of rat lung microvascular ECs with etanercept inhibited proinflammatory gene activation (E-selectin, intercellular adhesion molecule 1, interleukin 6, RhoB) and apoptosis during ischemic AKI. Ischemic AKI drives distinct proinflammatory and proapoptotic changes in the pulmonary EC transcriptome with TNFR1-dependent caspase activation and programmed cell death. Further investigation of potential EC mechanisms of kidney-lung crosstalk during AKI may identify potential therapeutic targets for this deadly disease. PMID- 22777114 TI - The fibrinopeptide bbeta15-42 reduces inflammation in mice subjected to polymicrobial sepsis. AB - Sepsis is still a leading cause of death on intensive care units. Despite intensive research, only few new therapies have been developed and used in the clinical setting. The fibrin fragment Bbeta15-42 was already shown to preserve endothelial barrier function by binding to VE-cadherin and thus stabilize the interendothelial junctions. This was accompanied by reduced inflammation. Now we show that treatment with Bbeta15-42 reduces inflammation in a murine polymicrobial sepsis model. Administration of Bbeta15-42 reduced proinflammatory cytokine levels in the lung, liver, and blood and decreased neutrophil infiltration into the lung. Analysis alanine aminotransferase and aspartate aminotransferase further indicated reduced liver damage following polymicrobial sepsis. In vitro experiments using endothelial cells and macrophages further revealed that Bbeta15-42 had no direct effect on Toll-like receptor-mediated inflammation. Therefore, we assume that attenuated inflammation is rather due to sustained vascular integrity and thus suppresses vascular leakage and subsequently leukocyte infiltration during sepsis. PMID- 22777113 TI - Resuscitation of traumatic hemorrhagic shock patients with hypertonic saline without dextran-inhibits neutrophil and endothelial cell activation. AB - Posttraumatic inflammation and excessive neutrophil activation cause multiple organ dysfunction syndrome (MODS), a major cause of death among hemorrhagic shock patients. Traditional resuscitation strategies may exacerbate inflammation; thus, novel fluid treatments are needed to reduce such posttraumatic complications. Hypertonic resuscitation fluids inhibit inflammation and reduce MODS in animal models. Here we studied the anti-inflammatory efficacy of hypertonic fluids in a controlled clinical trial. Trauma patients in hypovolemic shock were resuscitated in a prehospital setting with 250 mL of either 7.5% hypertonic saline (HS; n = 9), 7.5% hypertonic saline + 6% dextran 70 (HSD; n = 8), or 0.9% normal saline (NS; n = 17). Blood samples were collected on hospital admission and 12 and 24 h after resuscitation. Multicolor flow cytometry was used to quantify neutrophil expression of cell-surface activation/adhesion (CD11b, CD62L, CD64) and degranulation (CD63, CD66b, CD35) markers as well as oxidative burst activity. Circulating concentrations of soluble intercellular adhesion molecule-1 (sICAM 1), vascular cell adhesion molecule-1 (sVACM-1), P- and E-selectins, myeloperoxidase (MPO), and matrix metalloproteinase 9 (MMP-9) were assessed by immunoassay. Multiple organ dysfunction syndrome, leukocytosis, and mortality were lower in the HS and HSD groups than in the NS group. However, these differences were not statistically significant. Hypertonic saline prevented priming and activation and neutrophil oxidative burst and CD11b and CD66b expression. Hypertonic saline also reduced circulating markers of neutrophil degranulation (MPO and MMP-9) and endothelial cell activation (sICAM-1, sVCAM-1, soluble E-selectin, and soluble P-selectin). Hypertonic saline + 6% dextran 70 was less capable than HS of suppressing the upregulation of most of these activation markers. This study demonstrates that initial resuscitation with HS, but neither NS nor HSD, can attenuate posttraumatic neutrophil and endothelial cell activation in hemorrhagic shock patients. These data suggest that hypertonic resuscitation without dextran may inhibit posttraumatic inflammation. However, despite this effect, neither HS nor HSD reduced MODS in trauma patients with hemorrhagic shock. PMID- 22777115 TI - Ringer's malate solution protects against the multiple organ injury and dysfunction caused by hemorrhagic shock in rats. AB - Malic acid, in the form of its anion malate, is a key intermediate in the major biochemical energy-producing cycle known as the citric acid or Krebs cycle. In this study, the authors investigated the protective effect of a novel crystalloid solution of Ringer's malate following fluid resuscitation of hemorrhagic shock using a rat model. Under general anesthesia, Sprague-Dawley male rats were subjected to 60 min of hemorrhagic shock (40 mmHg for 60 min) followed by crystalloid resuscitation. Groups were as follows: (1) sham shock, (2) normal saline, (3) Ringer's lactate, and (4) Ringer's malate. The experiment was terminated at 4 h after resuscitation. Mean arterial blood pressure (MAP) and blood biophysical parameters were monitored during the experiment. The alanine aminotransferase, aspartate aminotransferase, urea, creatinine, superoxide dismutase, and malondialdehyde levels in plasma were detected. The intestine, liver, lung, and renal histopathology were measured. It was found that Ringer's malate could increase MAP immediately and maintain MAP for a long time. Ringer's malate could reduce the level of alanine aminotransferase, aspartate aminotransferase, urea, and creatinine. At the same time, the activity of superoxide dismutase was increased, and the level of malondialdehyde was decreased. Histopathology indicated that Ringer's malate can protect against the multiple organ injury caused by hemorrhagic shock in rats. Ringer's malate prevented circulatory failure and alleviated multiple organ dysfunction syndrome in animals with hemorrhagic shock. The study suggests that Ringer's malate solution could be a potential novel therapeutic agent for fluid resuscitation. PMID- 22777116 TI - Temperature and cell-type dependency of sulfide effects on mitochondrial respiration. AB - Previous studies suggest that sulfide-induced inhibition of cytochrome c oxidase (cCox) and, consequently, the metabolic and toxic effects of sulfide are less pronounced at low body temperature. Because the temperature-dependent effects of sulfide on the inflammatory response are still a matter of debate, we investigated the impact of varying temperature on the cCox excess capacity and the mitochondrial sulfide oxidation by the sulfide-ubiquinone oxidoreductase in macrophage-derived cell lines (AMJ2-C11 and RAW 264.7). Using an oxygraph chamber, the inhibition of mitochondrial respiration was measured by stepwise titrations with sulfide and the nonmetabolizable cCox inhibitor sodium azide at 25 degrees C and 37 degrees C. Using the latter of the two inhibitors, the excess capacity of the cCox was obtained. Furthermore, we quantified the capacity of these cells to withstand sulfide inhibition by measuring the amount required to inhibit respiration by 50% and 90% and the viability of the cells after 24-h exposure to 100 ppm of hydrogen sulfide. At low titration rates, the AMJ2-C11 cells, but not the RAW 264.7 cells, increased their capacity to withstand exogenously added sulfide. This effect was even greater at 25 degrees C than at 37 degrees C. Furthermore, only the AMJ2-C11 cells remained viable after sulfide exposure for 24 h. In contrast, only in the RAW 264.7 cells that an increase in cCox excess capacity was found at low temperatures. In macrophage-derived cell lines, both the excess capacity of cCox and the efficiency of sulfide elimination may increase at low temperatures. These properties may modify the effects of sulfide in immune cells and, potentially, the inflammatory response during sulfide exposure at different body temperatures. PMID- 22777117 TI - Glutamine modulates sepsis-induced changes to intestinal intraepithelial gammadeltaT lymphocyte expression in mice. AB - This study investigated the effect of glutamine (GLN) on intestinal intraepithelial lymphocyte (IEL) gammadeltaT-cell cytokines and immune regulatory factor gene expressions in a mouse model of polymicrobial sepsis. Mice were randomly assigned to a normal group, a sepsis with saline (SS) group, or a sepsis with GLN (SG) group. All mice were fed a chow diet. Sepsis was induced by cecal ligation and puncture (CLP). The SS group was injected with saline, and the SG group was given 0.75 g GLN/kg body weight once via a tail vein 1 h after CLP. Septic mice were killed 12 h after CLP, and IEL gammadeltaT cells of the animals were isolated for further analysis. Results showed that compared with normal mice, sepsis resulted in lower IEL gammadeltaT-cell percentage and higher messenger RNA expressions of interferon gamma, tumor necrosis factor alpha, interleukin 4 (IL-4), IL-13, IL-17, retinoid acid receptor-related orphan receptor gammat, and complement 5a receptor by IEL gammadeltaT cells. These immunomodulatory mediator genes exhibited decreases, whereas IL-7 receptor expression increased in IEL gammadeltaT cells in septic mice with GLN administration. Annexin V/7-amino-actinomycin D stain revealed significantly lower rates of apoptosis, and IEL gammadeltaT-cell percentage was higher in the SG group. The histological findings also showed that damage to intestinal epithelial cells was less severe in the SG group. These results indicated that a single dose of GLN administered as treatment after the initiation of sepsis prevented apoptosis of IEL gammadeltaT cells and downregulated gammadeltaT cell expressed inflammatory mediators that may consequently ameliorate the severity of sepsis-induced intestinal epithelial injury. PMID- 22777118 TI - Environmental hypothermia in porcine polytrauma and hemorrhagic shock is safe. AB - We have previously demonstrated survival benefit to induced hypothermia in a porcine model of controlled hemorrhagic shock simulating an associated delay to definitive care. In the current study, we wished to evaluate the effects of environmental hypothermia in a porcine model of hemorrhagic shock with the addition of polytrauma. Sixteen pigs were randomized to normothermic (39 degrees C, n = 7) or hypothermic (34 degrees C, n = 9) groups. The model included instrumentation, chest injury (captive bolt device), hemorrhage to systolic blood pressure (SBP) of ~50 mmHg, and crush liver injury. Animals received limited fluid resuscitation for a 1-h period with goal SBP of greater than 80 mmHg and ice packs or warming blankets to achieve goal temperatures, followed by full resuscitation with goal SBP of greater than 90 mmHg, adequate urine output, and hemoglobin by protocol for 20 h. Survivors were observed for an additional 24 h with end points including mortality, markers of organ injury, and neurologic function. There were no differences in survival between the groups (mortality = 1/9, hypothermia group vs. 2/7, normothermia group, P = 0.39). Markers of organ injury were elevated in the hypothermia group at 24 h after injury but were identical between groups at the end of the experimental protocol (48 h after injury). There were no noted differences in neurologic function between the two groups. Environmental hypothermia in a model of polytrauma and hemorrhagic shock was not associated with worse outcomes. PMID- 22777119 TI - Continuous enteral and parenteral feeding each reduces heart rate variability but differentially influences monocyte gene expression in humans. AB - Enteral (EN) or parenteral (PN) nutrition is used to support critically ill patients until oral feeding resumes. Enteral nutrition is assumed preferable to PN, but the differential influence on immune function is not well defined. Autonomic nervous activity is known to influence innate immune responses, and we hypothesized that EN and PN could influence both autonomic signaling and gene activation in peripheral blood monocytes (PBMs). Ten subjects (aged 18-36 years) received continuous EN or PN for 72 h. Peripheral blood monocytes were isolated from whole blood before and after continuous feeding and were analyzed for gene expression using a microarray platform. Gene expression after feeding was compared from baseline and between groups. To measure autonomic outflow, subjects also underwent heart rate variability (HRV) monitoring during feeding. Time and frequency domain HRV data were compared between groups and five orally fed subjects for changes from baseline and changes over time. During continuous EN and PN, subjects exhibited declines in both time and frequency domain HRV parameters compared with baseline and with PO subjects, indicating a loss of vagal/parasympathetic tone. However, PN feeding had a much greater influence on PBM gene expression compared with baseline than EN, including genes important to innate immunity. Continuous EN and PN are both associated with decreasing vagal tone over time, yet contribute differently to PBM gene expression, in humans. These preliminary findings support assumptions that PN imposes a systemic inflammatory risk but also imply that continuous feeding, independent of route, may impart additional risk through different mechanisms. PMID- 22777120 TI - Cyclin-dependent kinase inhibition reduces lung damage in a mouse model of ventilator-induced lung injury. AB - Mechanical ventilation (MV) has the potential to induce lung damage in healthy lungs or aggravate existing lung injury. Polymorphonuclear neutrophil (PMN) recruitment plays an important role in driving the inflammatory response in ventilator-induced lung injury (VILI). The cyclin-dependent kinase inhibitor r roscovitine has been shown to induce apoptosis in PMNs. In this study, we investigated the potential of r-roscovitine treatment in reducing lung damage in a mouse model of VILI. Mice were tracheotomized and subjected to lung-protective MV with lower (~7.5 mL/kg) or lung-injurious MV with higher (~15 mL/kg) tidal volume (VT). R-roscovitine treatment enhanced apoptosis in PMNs in vitro. Ventilator-induced lung injury was associated with pulmonary PMN influx in low and high VT MV. During lung-injurious MV, r-roscovitine treatment reduced the number of PMNs and lowered levels of the lung damage markers RAGE (receptor for advanced glycation end products) and total immunoglobulin M in bronchoalveolar lavage fluid. R-roscovitine did not affect cytokine or chemokine levels in the bronchoalveolar space, neither during lung-protective nor lung-injurious MV. Thus, r-roscovitine treatment reduces lung damage in VILI, possibly dependent on increased apoptosis of PMNs. PMID- 22777121 TI - STAT1-deficient mice are resistant to cecal ligation and puncture-induced septic shock. AB - STAT1 (signal transducer and activator of transcription 1) is a member of the JAK STAT signaling family and plays a key role in facilitating gene transcription in response to activation of the types I and II interferon (IFN) receptors. TYK2 is essential for type I, but not type II, IFN-induced STAT1 activation. Previous studies show that STAT1-deficient mice are resistant to endotoxin-induced shock. The goal of the present study was to assess the response of STAT1- and TYK2 deficient mice to septic shock caused by cecal ligation and puncture (CLP). End points included survival, core temperature, organ injury, systemic cytokine production, and bacterial clearance. Results showed that survival rates were significantly higher in STAT1 knockout (STAT1KO) mice compared with wild-type controls (80% vs. 10%). The improved survival of STAT1KO mice was associated with less hypothermia, metabolic acidosis, hypoglycemia, and hepatocellular injury. Plasma interleukin 6, MIP-2, CXCL10, and IFN-alpha concentrations were significantly lower in STAT1KO mice than in wild-type mice. In the absence of antibiotic treatment, blood and lung bacterial counts were significantly lower in STAT1KO mice than in controls. However, treatment with antibiotics ablated that difference. A survival advantage was not observed in TYK2-deficient mice compared with control. However, CLP-induced hypothermia and systemic interleukin 6 and CXCL10 production were significantly attenuated in TYK2-deficient mice. These results indicate that STAT1 activation is an important factor in the pathogenesis of CLP-induced septic shock and is associated with the development of systemic inflammation and organ injury. TYK2 activation also appears to contribute to CLP induced inflammation, but to a lesser extent than STAT1. PMID- 22777122 TI - Ischemic postconditioning during reperfusion attenuates intestinal injury and mucosal cell apoptosis by inhibiting JAK/STAT signaling activation. AB - The present study attempts to evaluate the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling in intestinal ischemia/reperfusion (I/R)-induced intestinal injury and whether immediate ischemic postconditioning ameliorates intestinal injury via attenuation of intestinal mucosal apoptosis subsequent to inhibiting JAK/STAT signaling activation. Anesthetized adult male Sprague-Dawley rats were subjected to superior mesenteric artery occlusion consisting of 60 min of ischemia and 2 h of reperfusion; sham laparotomy served as controls. Animals received either subcutaneous administration of JAK2 inhibitor (AG490, 8 mg/kg) or STAT inhibitor (rapamycin, 0.4 mg/kg) 30 min before ischemia. Ischemic postconditioning was performed by three cycles of 30-s reperfusion and 30-s ischemia initiated immediately upon reperfusion. It was found that intestinal I/R resulted in conspicuous intestinal injury evidenced by significant increases in Chiu's score, lactic acid, and diamine oxidase activity, accompanied with increases in plasma levels of 15-F2t-isoprostane, endothelin 1, and thromboxane B2, as well as increase in the intestinal tissue myeloperoxidase activity. Meanwhile, the apoptotic index and cleaved caspase 3, phosphorylated JAK2, phosphorylated STAT1, and phosphorylated STAT3 expression were significantly enhanced versus sham control. Both ischemic postconditioning and pretreatment with AG490 or rapamycin significantly attenuated all the above changes. These results indicate that JAK/STAT pathway activation plays a critical role in I/R-induced intestinal injury, which is associated with increased oxidative stress, neutrophil accumulation, intestinal mucosal apoptosis, and microcirculation disturbance. Ischemic postconditioning mediates attenuation of intestinal I/R injury, and cell apoptosis may be attributable to the JAK/STAT signaling inhibition. PMID- 22777123 TI - Role of peroxynitrite in sepsis-induced acute kidney injury in an experimental model of sepsis in rats. AB - The mechanisms involved in sepsis-induced acute kidney injury (AKI) are unknown. We investigated the role of nitrosative stress in sepsis-induced AKI by studying the effects of manganese (III) tetrakis-(1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), a peroxynitrite decomposition catalyst, and aminoguanidine (AG), a selective nitric oxide synthase 2 (NOS2) inhibitor and peroxynitrite scavenger, on kidney function of rats subjected to cecal ligation and puncture (CLP). Sprague-Dawley rats (weighing 350 [SD, 50] g) were treated with MnTMPyP (6 mg/kg i.p.) or AG (50 mg/kg i.p.) at t = 12 and 24 h after CLP or sham procedure. At t = 36 h, mean arterial pressure and aortic blood flow were measured, and blood and urine samples were obtained for biochemical determinations, including creatinine clearance, fractional excretion of sodium, and neutrophil gelatinase-associated lipocalin concentration in the urine. Kidney tissue samples were obtained for (i) light microscopy, (ii) immunofluorescence and Western blot for 3-nitrotyrosine and NOS2, (iii) gene expression (quantitative real-time polymerase chain reaction) studies (NOS1, NOS2, NOS3, and superoxide dismutase 1), and (iv) matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Mean arterial pressure was unchanged and aortic blood flow decreased 25% in CLP animals. The sepsis-induced (i) decreased urine output and creatinine clearance and increased fractional excretion of sodium and urinary neutrophil gelatinase-associated lipocalin concentration, (ii) increased protein nitration and NOS2 protein, and (iii) NOS1 and NOS2 upregulation were all significantly attenuated by treatment with MnTMPyP or AG. Nitrated proteins in renal tissue from CLP animals (matrix-assisted laser desorption ionization time of-flight mass spectrometry) were glutamate dehydrogenase, methylmalonate semialdehyde dehydrogenase, and aldehyde dehydrogenase, mitochondrial proteins involved in energy metabolism or antioxidant defense. Nitro-oxidative stress is involved in sepsis-induced AKI, and protein nitration seems to be one mechanism involved. PMID- 22777124 TI - Plasma levels of mitochondrial DNA in patients presenting to the emergency department with sepsis. AB - Elevated levels of plasma mitochondrial DNA (mtDNA) have been reported in trauma patients and may contribute to the systemic immune response. We sought to determine the plasma levels of mtDNA in emergency department (ED) patients with and without sepsis and evaluate their association with severity of illness. This was a prospective observational study of patients presenting to one of three large, urban, tertiary care EDs. Patients were enrolled into one of three cohorts: (i) sepsis defined as suspected infection and two or more systemic inflammatory response criteria without hypotension, (ii) septic shock defined as sepsis plus hypotension despite an adequate fluid challenge, and (iii) control defined as noninfected ED patients without systemic inflammatory response/hypotension. Plasma levels of three mtDNAs were measured using real-time quantitative polymerase chain reaction. Levels of mtDNAs were compared among the three cohorts, and linear regression was used to assess the association between mtDNAs, interleukin 6, interleukin 10, and Sequential Organ Failure Assessment (SOFA) scores in patients with sepsis. We enrolled 93 patients: 24 control subjects, 29 patients with sepsis, and 40 patients with septic shock. As expected, comorbidities and SOFA score increased across categories. We found no difference in mtDNA levels between the three groups (P = 0.14-0.30). Among patients with sepsis, we found a small but significant negative association between mtDNA level and SOFA score, most clearly with cytochrome b (P = 0.03). We found no difference in mtDNA levels between control subjects and patients with sepsis. Mitochondrial DNA levels were negatively associated with organ dysfunction, suggesting that plasma mtDNA does not significantly contribute to the pathophysiology of sepsis. PMID- 22777125 TI - Kinetics and equilibrium of solute diffusion into human hair. AB - The uptake kinetics of five molecules by hair has been measured and the effects of pH and physical chemical properties of molecules were investigated. A theoretical model is proposed to analyze the experimental data. The results indicate that the binding affinity of solute to hair, as characterized by hair water partition coefficient, scales to the hydrophobicity of the solute and decreases dramatically as the pH increases to the dissociation constant. The effective diffusion coefficient of solute depended not only on the molecular size as most previous studies suggested, but also on the binding affinity as well as solute dissociation. It appears that the uptake of molecules by hair is due to both hydrophobic interaction and ionic charge interaction. Based on theoretical considerations of the cellular structure, composition and physical chemical properties of hair, quantitative-structure-property-relationships (QSPR) have been proposed to predict the hair-water partition coefficient (PC) and the effective diffusion coefficient (D (e)) of solute. The proposed QSPR models fit well with the experimental data. This paper could be taken as a reference for investigating the adsorption properties for polymeric materials, fibres, and biomaterials. PMID- 22777126 TI - Comparing pre- and post-operative Fontan hemodynamic simulations: implications for the reliability of surgical planning. AB - Virtual modeling of cardiothoracic surgery is a new paradigm that allows for systematic exploration of various operative strategies and uses engineering principles to predict the optimal patient-specific plan. This study investigates the predictive accuracy of such methods for the surgical palliation of single ventricle heart defects. Computational fluid dynamics (CFD)-based surgical planning was used to model the Fontan procedure for four patients prior to surgery. The objective for each was to identify the operative strategy that best distributed hepatic blood flow to the pulmonary arteries. Post-operative magnetic resonance data were acquired to compare (via CFD) the post-operative hemodynamics with predictions. Despite variations in physiologic boundary conditions (e.g., cardiac output, venous flows) and the exact geometry of the surgical baffle, sufficient agreement was observed with respect to hepatic flow distribution (90% confidence interval-14 +/- 4.3% difference). There was also good agreement of flow-normalized energetic efficiency predictions (19 +/- 4.8% error). The hemodynamic outcomes of prospective patient-specific surgical planning of the Fontan procedure are described for the first time with good quantitative comparisons between preoperatively predicted and postoperative simulations. These results demonstrate that surgical planning can be a useful tool for single ventricle cardiothoracic surgery with the ability to deliver significant clinical impact. PMID- 22777129 TI - Small RNAs: piRNA surveillance in the C. elegans germline. PMID- 22777128 TI - The place of genetics in ageing research. AB - Rapidly increasing numbers of older people present many countries with growing social and economic challenges. Yet despite the far-reaching implications of ageing, its biological basis remains a topic of much debate. Recent advances in genomics have spurred research on ageing and lifespan in human populations, adding to extensive genetic studies being carried out in model organisms. But how far is ageing controlled by our genes? In this Viewpoint, six experts present their opinions and comment on future directions in ageing research. PMID- 22777130 TI - Interaction of CO and deuterium with bimetallic, monolayer Pt-island/film covered Ru(0001) surfaces. AB - The adsorption properties of structurally well defined bimetallic Pt/Ru(0001) surfaces, consisting of a Ru(0001) substrate partly or fully covered by monolayer Pt islands or a monolayer Pt film, were studied by temperature programmed desorption (TPD) using CO and deuterium as probe molecules. Additionally, the adsorption of CO was investigated by infrared reflection absorption spectroscopy (IRAS). The presence of the pseudomorphic platinum islands or monolayer film leads to considerable modifications of the adsorption properties for both adsorbates, both on the Pt covered and, to a smaller extent, on the bare Ru part of the surfaces. In addition to distinct weakly bound adspecies, which are adsorbed on the monolayer Pt islands, we find unique contributions from island edge desorption, from spill-over processes during the desorption run, and a general down-shift of the peak related to desorption from Pt-free Ru(0001) areas with increasing Pt coverage. These effects, which we consider as characteristic for adsorption on bimetallic surfaces with large contiguous areas of the respective types, are discussed in detail. PMID- 22777127 TI - Genetic architectures of psychiatric disorders: the emerging picture and its implications. AB - Psychiatric disorders are among the most intractable enigmas in medicine. In the past 5 years, there has been unprecedented progress on the genetics of many of these conditions. In this Review, we discuss the genetics of nine cardinal psychiatric disorders (namely, Alzheimer's disease, attention-deficit hyperactivity disorder, alcohol dependence, anorexia nervosa, autism spectrum disorder, bipolar disorder, major depressive disorder, nicotine dependence and schizophrenia). Empirical approaches have yielded new hypotheses about aetiology and now provide data on the often debated genetic architectures of these conditions, which have implications for future research strategies. Further study using a balanced portfolio of methods to assess multiple forms of genetic variation is likely to yield many additional new findings. PMID- 22777132 TI - Porous three-dimensional nanorod arrays through selective chemical etching of nanocomposites. AB - Three-dimensional Cu-Si and Cu-SiO(2) nanorod arrays containing ~68 at% Cu have been fabricated by a glancing angle co-deposition technique. By selectively etching Cu in 0.05 M KCN methanol solution, porous nanorods with different shapes form, which are promising for applications in sensors, catalysts, and as medical capsules that are able to be loaded with functional materials. PMID- 22777131 TI - Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy. AB - OBJECTIVES: To evaluate the safety and tolerability of treatment with levetiracetam and determine the trough levels of levetiracetam in patients with traumatic brain injury (TBI) who are at high risk for posttraumatic epilepsy (PTE). DESIGN: Open-label, nonrandomized phase 2 study with 2 arms comparing levetiracetam treatment vs observation. SETTING: Two level 1 trauma centers. PATIENTS: A total of 422 participants 6 years or older with TBI who have a 20% risk for PTE were screened. Of these participants, 205 (48.6%) were eligible. A total of 126 participants were enrolled: 86 adults and 40 children. A total of 66 participants were in the treatment group (46 adults and 20 children), and a total of 60 participants were in the observation group (40 adults and 20 children). Participants presenting within 8 hours after TBI received treatment, and those presenting more than 8 to 24 hours after TBI did not. INTERVENTION: Treatment with levetiracetam (55 mg/kg/d) for 30 days starting within 8 hours after injury. MAIN OUTCOME MEASURES: Number of adverse events, mood score, number of infections, trough level of levetiracetam, and PTE. RESULTS: Of the 66 participants treated with levetiracetam, 2 (3%) stopped treatment owing to toxicity (somnolence). The most common adverse events were fatigue, headache, and somnolence. Mood scores and number of infections did not differ between the treatment and observation groups. Mean trough levels of levetiracetam on days 2 to 30 ranged from 19.6 to 26.7 MUg/mL. At 2 years, 13 of 86 adults (15.1%) and 1 of 40 children (2.5%) developed PTE. At 2 years, 5 of 46 treated adults (10.9%) and 8 of 40 untreated adults (20.0%) developed PTE (relative risk, 0.47; P=.18). CONCLUSION: Treatment with 55 mg/kg/d of levetiracetam (a dose with an antiepileptogenic effect on animals) for patients with TBI at risk for PTE is safe and well tolerated, with plasma levels similar to those in animal studies. The findings support further evaluation of levetiracetam treatment for the prevention of PTE. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01463033. PMID- 22777133 TI - Controlling the bleeding of jejunal varices formed at the site of choledochojejunostomy: report of 2 cases and a review of the literature. AB - INTRODUCTION: Hemorrhage from jejunal varices formed at the site of Roux-en-Y choledochojejunostomy is rather rare, and no guidelines have so far been established for its treatment. This report presents the cases of 2 patients with jejunal varices formed at the site of choledochojejunostomy that were treated using different methods. An obstruction of the extrahepatic portal vein resulted in massive gastrointestinal bleeding in both cases CASE 1: A 59-year-old male developed jejunal varices at the site of choledochojejunostomy. Multidetector computed tomography showed that the source of bleeding was located in the small intestine near portojejunal varices. The jejunal vein supplying the afferent loop was embolized using interventional radiology. There was no evidence of liver dysfunction or rebleeding after the embolization CASE 2: A 79-year-old female developed jejunal varices at the site of choledochojejunostomy. Abdominal angiography could not detect the source of bleeding, and hence, a mesocaval shunt operation was performed. PMID- 22777134 TI - Successful lung autotransplantation for central non-small-cell lung cancer: report of a case. AB - Non-small-cell lung cancer (NSCLC) confined to the lung is generally treated by surgical resection. The extent of resection is determined by the location of the tumor and the patient's pulmonary function. This report presents a successful lung autotransplantation in a man with NSCLC that could not tolerate pneumonectomy or sleeve lobectomy. Right upper and middle bilobectomies were performed, the right lower lobe was resected and retrograde perfusion of Raffinose low-potassium dextran solution (4 degrees C) was administered. The isolated lower lobe was reimplanted by anastomosis of the bronchus, pulmonary artery, and vein. The patient was cancer-free 1 year after the surgery. Lung autotransplantation can therefore be successfully performed for selected patients with central NSCLC. PMID- 22777135 TI - Fetal cardiac function: M-mode and 4D spatiotemporal image correlation. AB - Fetal cardiac function has been shown to be a marker of disease severity in many conditions, including intrauterine growth restriction, congenital heart defects or disease (CHD), twin-to-twin transfusion syndrome, idiopathic hydrops, fetal arrhythmias, and others. It is often targeted for evaluation of patient management, for providing complete and accurate diagnoses in CHD, for patient counseling, or in referring for fetal cardiac interventions. In this review we will describe the use of M-mode and 4D spatiotemporal image correlation in fetal cardiac evaluation, the parameters that can be measured, and their application to clinical practice. PMID- 22777136 TI - An electrokinetically tunable optofluidic bi-concave lens. AB - This paper numerically and experimentally investigates and demonstrates the design of an optofluidic in-plane bi-concave lens to perform both light focusing and diverging using the combined effect of pressure driven flow and electro osmosis. The concave lens is formed in a rectangular chamber with a liquid core liquid cladding (L(2)) configuration. Under constant flow rates, the performance of the lens can be controlled by an external electric field. The lens consists of a core stream (conducting fluid), cladding streams (non-conducing fluids), and auxiliary cladding streams (conducting fluids). In the focusing mode, the auxiliary cladding stream is introduced to sandwich the biconcave lens to prevent light rays from scattering at the rough chamber wall. In the diverging mode, the auxiliary cladding liquid has a new role as the low refractive-index cladding of the lens. In the experiments, the test devices were fabricated in polydimethylsiloxane (PDMS) using the standard soft lithography technique. Ethanol, cinnamaldehyde, and a mixture of 73.5% ethylene glycol and 26.5% ethanol work as the core stream, cladding streams and auxiliary cladding streams. In the numerical simulation, the electric force acts as a body force. The governing equations are solved by a finite volume method on a Cartesian fixed staggered grid. The evolution of the interface was captured by the level set method. The results show that the focal length in the focusing mode and the divergent angle of the light beam in the diverging mode can be tuned by adjusting the external electric field at fixed flow rates. The numerical results have a reasonable agreement with the experimental results. PMID- 22777137 TI - A patient with a dysembryoplastic neuroepithelial tumor who underwent epilepsy surgery after initial seizure. AB - BACKGROUND: Since dysembryoplastic neuroepithelial tumors (DNTs) are benign tumors that are frequently associated with long-standing medically intractable epilepsy, it is well known that the surgical strategy is resection of the associated epileptogenic zone as well as the tumor. However, the surgical strategy for DNT with a single seizure has not been fully discussed. METHODS: We report an 8-year-old boy with DNT in the nondominant frontal lobe who underwent epilepsy surgery at 3 months after his initial seizure. RESULTS: An intraoperative electrocorticogram revealed frequent paroxysmal cortical activity lateral to the tumor. Since resection of the tumor resulted in persistent paroxysmal activity in this cortex, additional resection was performed. The histological findings in the cortex revealed the presence of cortical dysplasia (CD) (Palmini type IIA). Lesionectomy alone might have left the epileptogenic CD. CONCLUSION: It is thought that epilepsy surgery should be recommended in patients with typical neuroimaging findings of DNT, even if the patients had only one episode of seizure. PMID- 22777138 TI - Carbonate, acetate and phenolate phosphonium salts as catalysts in transesterification reactions for the synthesis of non-symmetric dialkyl carbonates. AB - Methyl trioctylphosphonium methyl carbonate [P(8881)](+)[MeOCO(2)](-) was prepared by the alkylation of trioctyl phosphine with the non-toxic dimethyl carbonate. This salt was a convenient source to synthesize different ionic liquids where the methyl trioctylphosphonium cation was coupled to weakly basic anions such as bicarbonate, acetate, and phenolate. At 90-220 degrees C, all these compounds [P(8881)](+)X(-); X = MeOCO(2); HOCO(2); AcO; PhO were excellent organocatalysts for the transesterification of dimethyl and diethyl carbonate with primary and secondary alcohols, including benzyl alcohol, cyclopentanol, cyclohexanol, and the rather sterically hindered menthol. Conditions were optimized to operate with very low catalyst loadings up to 1 mol% and to obtain non-symmetric dialkyl carbonates (ROCO(2)R'; R = Me, Et) with selectivity up to 99% and isolated yields >90%. The catalytic performance of the investigated ionic liquids was discussed through a cooperative mechanism of simultaneous activation of both electrophilic and nucleophilic reactants. PMID- 22777139 TI - Anti-inflammatory effect of the endocannabinoid anandamide in experimental periodontitis and stress in the rat. AB - OBJECTIVE: Periodontitis is an infectious disease leading to inflammation and destruction of tissue surrounding and supporting the tooth. The progress of the inflammatory response depends on the host's immune system and risk factors such as stress. The aim of the present study was to investigate the role of the endocannabinoid anandamide (AEA) in experimental periodontitis with restraint stress, since the endocannabinoid system is known to modulate the hypothalamo pituitary-adrenal axis as well as immune functions and has been found in human gingival tissues. METHODS: Experimental periodontitis was induced by ligature around first inferior molars and immobilization stress for 2 h twice daily for 7 days in a rat model. RESULTS: Corticosterone plasma levels, locomotor activity, adrenal gland weight and bone loss were increased in periodontitis and stress groups, and there was also less weight gain. The inflammatory parameters such as prostaglandin E(2) (radioimmunoassay), nitric oxide (radioconversion of (14)C arginine), tumor necrosis factor (TNF)-alpha (ELISA) and interleukin (IL)-1beta (Western blot) measured in the gingival tissue were significantly increased in the periodontitis groups compared to the control group. Local injection of AEA (10(-8)M, 30 ul) decreased corticosterone plasma levels and the content of the cytokines TNF-alpha and IL-1beta in gingival tissue in periodontitis-stress groups. These AEA-induced inhibitions were mediated by CB(1) and CB(2) cannabinoid receptors since the injection of both antagonists together, AM251 (10(-6)M) and AM630 (10(-6)M) in 30 ul, prevented these effects. CONCLUSION: The endocannabinoid AEA diminishes the inflammatory response in periodontitis even during a stressful situation. PMID- 22777140 TI - Motor coordination, working memory, and academic achievement in a normative adolescent sample: testing a mediation model. AB - The aim of the present study was to examine whether the relationship between motor coordination and academic achievement is mediated by working memory (WM) in a normative adolescent sample. Participants included 93 adolescents aged 12-16. The Movement Assessment Battery for Children-2 provided three indicators of motor coordination (Manual Dexterity, Aiming and Catching, and Balance), the WM Index of the Wechsler Intelligence Scale for Children-IV and the N-back paradigm provided two indicators of WM, and the Wechsler Individual Achievement Test-II provided three indicators of academic achievement (Word Reading, Spelling, and Numerical Operations). Structural equation modeling, controlling for verbal comprehension, attention deficit hyperactivity disorder symptoms, and socioeconomic status, suggested that the association between motor coordination and academic achievement may be best understood in terms of a mechanism whereby motor coordination (specifically, Aiming and Catching skills) has an indirect impact on academic outcomes via WM. These findings have important implications for the assessment and treatment of motor coordination and learning difficulties as well as in increasing the understanding of the possible neural mechanisms underpinning the relationship between these areas. PMID- 22777141 TI - Clinical utility of reliable digit span in assessing effort in children and adolescents with epilepsy. AB - The assessment of effort is an important aspect of a comprehensive neuropsychological evaluation, as this can significantly impact data interpretation. While recent work has validated the appropriateness of adult derived cutoffs for standalone effort measures in younger populations, little research has focused on embedded effort measures in children. The present study includes 54 clinically referred children and adolescents (32 males/22 females; aged 6-17) with a confirmed diagnosis of epilepsy. Reliable Digit Spans (RDSs) were calculated and the Test of Memory Malingering (TOMM) was administered in the context of a comprehensive neuropsychological evaluation. Using a previously published RDS cutoff of <=6, a pass rate of only 65% was obtained, well below the recommended 90% pass rate for an effective effort index. In contrast, when adult criteria were used on TOMM Trial 2, a 90% pass rate was observed. RDS scores were significantly correlated with IQ estimates (r = .59, p < .001) and age (r = .61, p < .001). The difference between RDS and the TOMM on the participant outcome was statistically significant (chi(2) = 9.05, p = .003). These results suggest that RDS appears to yield a large number of false positives and, therefore, may be of limited utility in detecting poor effort in a pediatric epilepsy population. These findings likely extend to other pediatric populations that are known to have significant cognitive loss. PMID- 22777142 TI - Isolation of functional presynaptic complexes from CNS neurons: a cell-free preparation for the study of presynaptic compartments In vitro. AB - The difficulty in developing successful treatments to facilitate nerve regeneration has prompted a number of new in vitro experimental methods. We have recently shown that functional presynaptic boutons can be formed when neuronal cells are cocultured with surface-modified artificial substrates including poly(d lysine)-coated beads and supported lipid bilayer-coated beads (Lucido(2009) J. Neurosci.29, 12449-12466; Gopalakrishnan(2010) ACS Chem. Neurosci.1, 86-94). We demonstrate here, using confocal microscopy combined with immunocytochemistry, that it is possible to isolate such in vitro presynaptic endings in an exclusive fashion onto glass substrates through a simple "sandwich/lift-off" technique (Perez(2006) Adv. Funct. Mater.16, 306-312). Isolated presynaptic complexes are capable of releasing and recycling neurotransmitter in response to an external chemical trigger. These bead-presynaptic complexes are facile to prepare and are readily dispersible in solution. They are thus compatible with many experimental methods whose focus is the study of the neuronal presynaptic compartment. PMID- 22777143 TI - Use of nonabsorbable staples for urinary diversion: a step in the wrong direction. AB - BACKGROUND: The use of bowel segments incorporated into the urinary tract is well established in urological surgery. OBJECTIVE: To describe and compare the use of absorbable and nonabsorbable staples for creation of a urine reservoir after radical cystectomy. MATERIALS AND METHODS: This review is based on a systematic Medline search assessing the period 1950-2010. RESULTS: Use of the autosuture stapling device for the construction of the urinary diversion significantly reduces operating time. Johnson and Fuerst reported its use for the first time to construct a ureteroileocutaneous urinary diversion in 1973. However, many studies demonstrated that exposed metal staples represent a nidus for stone formation when they are in direct contact with urine, particularly in urinary diversions such as Kock pouch and ileal conduit. Stone formation has been attributed in part to the use of nonabsorbable artificial materials, such as metal staples and Marlex mesh, strictures of the pouch and accumulation of mucus. The treatment options for pouch calculi include observation for spontaneous passage, extracorporeal shockwave lithotripsy, percutaneous or endoscopic lithotripsy/lithotomy. CONCLUSIONS: Historically, the mean time to stone formation with nonabsorbable material (staples, Marlex mesh) is 34 months. None of the studies on use of nonabsorbable staples in urinary diversion has such a long follow-up. Until further studies with more appropriate observation time are completed, the use of nonabsorbable staples for continent and noncontinent urinary diversion should be discouraged. PMID- 22777144 TI - Acetylcholine and the alpha 7 nicotinic receptor: a potential therapeutic target for the treatment of periodontal disease? AB - OBJECTIVES: The aim of this review is to examine the evidence for a functional cholinergic system operating within the periodontium and determine the evidence for its role in periodontal immunity. INTRODUCTION: Acetylcholine can influence the immune system via the 'cholinergic anti-inflammatory pathway'. This pathway is mediated by the vagus nerve which releases acetylcholine to interact with the alpha7 subunit of the nicotinic acetylcholine receptor (alpha7nAChR) on proximate immuno-regulatory cells. Activation of the alpha7nAChR on these cells leads to down-regulated expression of pro-inflammatory mediators and thus regulates localised inflammatory responses. The role of the vagus nerve in periodontal pathophysiology is currently unknown. However, non-neuronal cells can also release acetylcholine and express the alpha7nAChR; these include keratinocytes, fibroblasts, T cells, B cells and macrophages. Therefore, by both autocrine and paracrine methods non-neuronal acetylcholine can also be hypothesised to modulate the localised immune response. METHODS: A Pubmed database search was performed for studies providing evidence for a functional cholinergic system operating in the periodontium. In addition, literature on the role of the 'cholinergic anti inflammatory pathway' in modulating the immune response was extrapolated to hypothesise that similar mechanisms of immune regulation occur within the periodontium. CONCLUSION: The evidence suggests a functional non-neuronal 'cholinergic anti-inflammatory pathway' may operate in the periodontium and that this may be targeted therapeutically to treat periodontal disease. PMID- 22777145 TI - The effect of sRAGE-Fc fusion protein attenuates inflammation and decreases mortality in a murine cecal ligation and puncture model. AB - OBJECTIVE: Inhibition of the receptor for advanced glycation end products (RAGE) may attenuate the systemic inflammatory response and ensuing severe sepsis. We report an investigation into the effect of soluble RAGE (sRAGE)-Fc fusion protein in severe sepsis induced by a cecal ligation and puncture (CLP) procedure. MATERIALS AND METHODS: The experiment was performed using CLP control mice, mice treated with 0.5 or 1.0 MUg sRAGE-Fc fusion protein, and sham surgery mice. RESULTS: Survival benefits over the CLP control group were evident (P = 0.036) in mice given 1.0 MUg sRAGE-Fc fusion protein. In addition, the pulmonary inflammation score in the sRAGE-Fc fusion protein-treated group was significantly lower than that in the CLP control group (P < 0.05). Lung tissue in the sRAGE-Fc fusion protein-treated group revealed a significant decrease in the expression of inflammatory cytokines. Furthermore, levels of interleukin (IL)-1beta and tumor necrosis factor-alpha were significantly lower in sRAGE-Fc fusion protein treated groups (P < 0.001). Moreover, IL-6 levels showed a significant difference between CLP control and sRAGE-Fc fusion protein treated groups (P < 0.01). CONCLUSIONS: sRAGE-Fc fusion protein has beneficial effects in a standard murine model of polymicrobial, intra-abdominal severe sepsis. PMID- 22777147 TI - Endovascular abdominal aortic aneurysm repair: surveillance of endoleak using maximum transverse diameter of aorta on non-enhanced CT. AB - BACKGROUND: Repeat volumetric analysis of abdominal aortic aneurysm (AAA) after endovascular AAA repair (EVAR) is time-consuming and requires advanced processing, dedicated equipment, and skilled operators. PURPOSE: To clarify the validity of measuring the maximal short-axis diameter (Dmax) of AAA in follow-up non-enhanced axial CT as a means of detecting substantial endoleaks after EVAR. MATERIAL AND METHODS: CT images were retrospectively reviewed in 47 patients (7 women, 40 men; mean age, 76.2 years) who had no endoleak on initial contrast enhanced CT after EVAR. Regular follow-up CT studies were performed every 6 months. At each CT study, the Dmax on the CT axial image was measured and compared with that on the last CT (115 data-sets). Contrast-enhanced CT was regarded as the standard of reference to decide the presence or absence of endoleaks. The appearance of endoleak was defined as the end point of this study. RESULTS: Endoleaks were detected in 17 patients during the follow-up period. Mean Dmax changes for 6 months were significant between positive and negative endoleak cases (1.8 +/- 1.9 vs. -1.1 +/- 3.0 mm, P < 0.0001). When the Dmax change <= 0 mm for 6 months was used as the threshold for negative endoleak, the sensitivity, specificity, positive predictive value, and negative predictive value were 74.5, 82.4, 96.1, and 35.9%, respectively. When Dmax change <=-1 mm was used as the threshold, the sensitivity, specificity, PPV, and NPV were 38.8, 100, 100, and 22.1%, respectively. CONCLUSION: Contrast-enhanced CT is not required for the evaluation of endoleaks when the Dmax decreases by at least 1 mm over 6 months after EVAR. PMID- 22777148 TI - Rate of onset of inhibition of gut-wall and hepatic CYP3A by clarithromycin. AB - AIMS: To determine the extent and time-course of hepatic and intestinal cytochrome P450 3A (CYP3A) inactivation due to the mechanism-based inhibitor clarithromycin. METHODS: Intestinal and hepatic CYP3A inhibition was examined in 12 healthy volunteers following the administration of single and multiple doses of oral clarithromycin (500 mg). Intestinal biopsies were obtained under intravenous midazolam sedation at baseline and after the first dose, on days 2-4, and on days 6-8 of the clarithromycin treatment. The formation of 1' hydroxymidazolam in biopsy tissue and the serum 1'-hydroxymidazolam:midazolam ratio were indicators of intestinal and hepatic CYP3A activity, respectively. RESULTS: Intestinal CYP3A activity decreased by 64 % (p = 0.0029) following the first dose of clarithromycin, but hepatic CYP3A activity did not significantly decrease. Repeated dosing of clarithromycin caused a significant decrease in hepatic CYP3A activity (p = 0.005), while intestinal activity showed little further decline. The CYP3A5 or CYP3A4*1B genotype were unable to account for inter-individual variability in CYP3A activity. CONCLUSIONS: Following the administration of clarithromycin, the onset of hepatic CYP3A inactivation is delayed compared to that of intestinal CYP3A. The time-course of drug-drug interactions due to clarithromycin will vary with the relative contribution of intestinal and hepatic CYP3A to the clearance and bioavailability of a victim substrate. PMID- 22777150 TI - Roxithromycin-induced toxic epidermal necrolysis. AB - This case report highlights a very rare adverse drug reaction of oral roxithromycin causing toxic epidermal necrolysis (TEN). A 54-year-old male patient diagnosed with upper respiratory tract infection was prescribed oral roxithromycin 150 mg twice daily for 7 days. On the 10th day, the patient was admitted to the emergency with sore throat, redness, watering of eyes, painful micturition, and severe skin lesions. The skin lesions were multiple, severely painful, burning, coalesced, and filled with fluid-producing large blisters appearing on the lip, face, and trunk and then gradually spreading to legs, arms, palms, hands, and feet extensively involving much >30% of body surface area. Clinical examination, blood investigation, and histopathological examination of the skin confirmed the diagnosis of TEN. There was no history of any concomitant medications, drug allergy, burn injury, recent graft, or transplant or any coexisting infections such as herpes simplex. Other resembling skin diseases were eliminated after proper dermatological examination. This episode of TEN was probably drug (roxithromycin) induced. The drug was immediately stopped, and the patient was treated meticulously resulting in gradual reversal of the diseased state. Naranjo adverse drug reaction probability scale suggested the likelihood that oral administration of roxithromycin was responsible for the TEN was 'probable.' PMID- 22777149 TI - Effect of treatment with pravastatin or ezetimibe on endothelial function in patients with moderate hypercholesterolemia. AB - BACKGROUND/AIM: Statin treatment improves endothelial function. It is matter of debate, however, if this effect of statins is due to their action on low-density lipoprotein cholesterol (LDL-C) or to other non-lipidic (pleiotropic) effects. The aim of this study was to evaluate whether the effect of pravastatin on endothelial function is mediated by pleiotropic effects. We therefore compared the effect of pravastatin and ezetimibe, a cholesterol absorption inhibitor, at doses yielding similar reductions in LDL-C and examined the effect of the two treatments on flow-mediated dilation (FMD) in hypercholesterolemic subjects. METHODS: A total of 33 moderately hypercholesterolemic patients were randomized into three treatment groups to receive ezetimibe 10 mg/day (n = 10), pravastatin 10 mg/day (n = 13) or no treatment (control, n = 10) for 6 weeks. To assess endothelial function, we determined FMD of the brachial artery non-invasively by high-resolution ultrasound before and after treatment. RESULTS: Ezetimibe and pravastatin treatment reduced LDL-C (mean +/- standard error) to a similar extent (-20.6 +/- 4.1 vs. -24.1 +/- 4.0 %, respectively; P = 0.4771), while no decrease was observed in the control group. FMD increased significantly after treatment with ezetimibe (from 11.4 +/- 5.7 to 16.8 +/- 3.6 %; P = 0.022) and with pravastatin (from 13.7 +/- 4.9 to 17.5 +/- 4.4 %; P = 0.0466), but not in the control group. There were no differences in the endothelial function changes between the two treatment groups. CONCLUSIONS: In this study, two treatments that lower cholesterol via different mechanisms improved endothelial function to a similar extent, suggesting that the observed effect can be explained by the reduction of cholesterol levels. PMID- 22777151 TI - Postpartum maternal codeine therapy and the risk of adverse neonatal outcomes: the devil is in the details. PMID- 22777152 TI - Plasma concentrations of quetiapine, N-desalkylquetiapine, o-desalkylquetiapine, 7-hydroxyquetiapine, and quetiapine sulfoxide in relation to quetiapine dose, formulation, and other factors. AB - BACKGROUND: N-Desalkylquetiapine may be a pharmacologically active quetiapine metabolite. However, information on plasma concentrations of N-desalkylquetiapine and other quetiapine metabolites attained during quetiapine therapy is scant. The aim of this study was to investigate plasma concentrations of quetiapine, N desalkylquetiapine, O-desalkylquetiapine, 7-hydroxyquetiapine, and quetiapine sulfoxide attained during therapy and analyze the data with respect to prescribed dose and other variables. METHOD: Quetiapine and its metabolites were measured in plasma samples submitted for quetiapine therapeutic drug monitoring (2009-2011). Concentration, metabolic ratio, and concentration corrected for dose (C/D) were investigated against quetiapine dose, age, sex, and formulation. Sample results were excluded if nonadherence with therapy was queried. RESULTS: There were 99 samples from 59 patients. N-Desalkylquetiapine plasma concentrations showed the strongest correlation with dose of all analytes, but O-desalkylquetiapine and quetiapine sulfoxide were strongly correlated to plasma quetiapine concentrations. There was no significant difference in C/D for any analyte between males and females and no correlation to age. Quetiapine and quetiapine sulfoxide C/D were significantly different (P < 0.01) between patients prescribed immediate- and extended-release formulations. Quetiapine, 7-hydroxyquetiapine and quetiapine sulfoxide C/D showed significant variation (P < 0.02) between those samples taken 10-14 hours postdose as compared with that of 16-24 hours postdose, but there was no significant effect as regards N-desalkylquetiapine. CONCLUSIONS: Plasma quetiapine, O-desalkylquetiapine, 7-hydroxyquetiapine, and quetiapine sulfoxide concentrations were significantly affected by formulation and/or time since last dose. Plasma N-desalkylquetiapine concentrations were not affected by either factor therefore may be a better marker for quetiapine exposure than plasma quetiapine concentrations. PMID- 22777153 TI - Endoxifen levels and its association with CYP2D6 genotype and phenotype: evaluation of a southern Brazilian population under tamoxifen pharmacotherapy. AB - BACKGROUND: An association between CYP2D6 variation and clinical outcomes among women with breast cancer treated with tamoxifen (TAM) has been demonstrated, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes. This association is mainly due to the CYP2D6-mediated hydroxylation of N-desmethyltamoxifen (NDT) to yield endoxifen (EDF), which because of its high antiestrogenic potency, is mainly responsible for the therapeutic efficacy of TAM. The aim of this study was to evaluate the relation of CYP2D6 genotyping and phenotyping with EDF levels and [NDT]/[EDF] metabolic ratio in breast cancer patients from South of Brazil under TAM therapy. METHODS: Trough blood samples were collected from 97 patients. CYP2D6 genotyping was performed with a luminex assay and calculation of genotypic activity scores. Tamoxifen and metabolites EDF, NDT, and 4-hydroxy-TAM were measured in plasma by high performance liquid chromatography with photo diode array detector. CYP2D6 phenotyping was performed by the determination of dextromethorphan (DMT) and dextrorphan (DTF) by high-performance liquid chromatography with fluorescence detection at plasma collected 3 hours after oral administration of 33 mg of DMF. Phenotypes were given according to [DMT]/[DTF] metabolic ratio. RESULTS: CYP2D6 genotyping indicated a prevalence of 4.1% poor metabolizer, 4.1% intermediate metabolizer, 49.5% extensive metabolizer slow activity, 39.2% extensive metabolizer fast activity, and 3.1% ultrarapid metabolizer. Genotype (genotypic activity scores) was significantly correlated with phenotype ([DMT]/[DTF]), with a moderate association (rs = -0.463; P < 0.001). Median plasma concentrations (nanograms per milliliter; N = 97) were TAM 57.17; 4-hydroxy-TAM 1.01; EDF 6.21; NDT 125.50. EDF levels were lower in poor metabolizers than that in extensive metabolizers (P < 0.05). Phenotype showed stronger, but still moderate, association with EDF and [NDT]/[EDF] than genotype (r = -0.507, r = 0.625, P < 0.001 versus r = 0.356, r = 0.516, P < 0.01). Phenotype accounted for 26% of the variability in EDF levels and 38% of [NDT]/[EDF], whereas genotype accounted for 12% and 27%, respectively. CONCLUSIONS: CYP2D6 genotyping and/or phenotyping could not fully predict EDF concentrations. Monitoring EDF itself could be considered during TAM therapy. PMID- 22777154 TI - Pharmacokinetic variability of four newer antiepileptic drugs, lamotrigine, levetiracetam, oxcarbazepine, and topiramate: a comparison of the impact of age and comedication. AB - BACKGROUND: Newer antiepileptic drugs (AEDs) are widely used in patients with epilepsy. There is still insufficient documentation regarding pharmacokinetic variability of these AEDs in different patient groups. PURPOSE: The purpose of this study was to compare age and comedication as factors contributing to pharmacokinetic variability between 4 newer AEDs (lamotrigine, levetiracetam, oxcarbazepine, and topiramate) among patients with refractory epilepsy. METHODS: Data regarding age, gender, use of AEDs, daily doses, and serum concentration measurements were retrieved from a therapeutic drug monitoring database, from patients admitted to the National Center for Epilepsy, Norway, 2007-2008. RESULTS: In total, 1050 patients were included, 111 younger children (2-9 years), 137 older children (10-17 years), 720 adults (18-64 years), 82 elderly (65-93 years). Fifty percent of the patients were prescribed polytherapy, in 88 different combinations. The interindividual pharmacokinetic variability was extensive, as illustrated by a 10-fold variability in serum concentration compared with dose. Age affected the apparent clearance of levetiracetam to the largest extent, as shown by a 60% increase in younger children and a 40% reduction in the elderly, respectively, compared with adults. Comedication altered the clearance of lamotrigine to the greatest extent +/-70% because it is affected by both enzyme inducers and inhibitors. Hepatic enzyme inducers increased the clearance of levetiracetam and topiramate by 25% and oxcarbazepine by 75%. Valproic acid reduced the clearance of topiramate by 25%. CONCLUSION: Age and comedication are important contributors to pharmacokinetic variability. Age had the greatest impact on levetiracetam, and comedication affected the clearance of each of the 4 AEDs investigated in this study. Pharmacokinetic drug interactions must be carefully considered when multidrug therapies are prescribed. Therapeutic drug monitoring is a valuable tool for individualizing AED therapy. PMID- 22777155 TI - The pharmacokinetics of prednisolone and prednisone in adult liver transplant recipients early after transplantation. AB - BACKGROUND: Glucocorticoids represent a cornerstone in the immunosuppressive therapy after solid organ transplantation. Interconversion between active and inactive states of glucocorticoids (ie, prednisolone and prednisone) is catalyzed by the enzymes 11beta-hydroxysteroid dehydrogenases 1 and 2. MATERIALS: This study investigated the pharmacokinetics of prednisolone and prednisone in 16 liver transplant recipients. Blood samples were collected in four 12-hour dosing intervals during the first 3 weeks posttransplant, including samples drawn at 13 time points. RESULTS: Area under the time-concentration curve of prednisolone was 3-13 MUg.h.mL.mg.kg with maximum concentrations (Cmax) between 0.37 and 2.5 MUg.mL.mg.kg and trough concentrations (C0) between 0.13 and 1.1 MUg.mL.mg.kg. The elimination half-lives were 1.9-10.3 hours. Apparent volume of distribution (VD/F) and apparent clearance (Cl/F) were 23-159 L and 4.7-28.7 L/h, respectively. CONCLUSIONS: This study demonstrated large intraindividual and interindividual variabilities in glucocorticoid pharmacokinetics. The results suggest that current prednisolone dosing early after liver transplantation might be too high, in particular when coadministered with methylprednisolone. These findings indicate a potential for improvement by personalized dosing of glucocorticoids in organ transplantation. PMID- 22777156 TI - 4-1BB-mediated signals confer protection against folic acid-induced nephrotoxicity. AB - BACKGROUND: The role of co-stimulatory molecules in renal diseases has been previously examined, however, little is known about the role of 4-1BB in the context of renal diseases resulting from nonimmune-mediated tubulointerstitial fibrosis. Folic acid induced Nephrotoxicity (FAN) in mice was used to explore the role of 4-1BB in this setting. METHODS: CD1 mice were treated with folic acid and kidneys subsequently examined using histochemistry, in addition to defining T cell profiles and evaluating renal function. Increased CD3+ and CD4+ T lymphocytes present in blood and spleen at day 3 suggested immunopathological reactions during the early stages of FAN and decreased CD3+ and CD4+ T lymphocytes on day 14 were characteristic of an immunocompromised state observed during the late stages of FAN. RESULTS: After 14 days of co-treatment with agonistic anti-4-1BB monoclonal antibodies, renal tubulointerstitial lesions were reduced. Renal function was improved, with Bun scores decreasing (p<0.01) and sCr levels decreasing (p<0.01). CD3+ and CD4+ T lymphocytes levels were increased during the early stages of disease in FA treated mice and reduced to the normal level in the 4-1BB-treated mice. CD3+ and CD4+ T lymphocytes levels were decreased in FA treated mice and returned to baseline in the 4-1BB-treated mice during later stages. CONCLUSIONS: Data presented in this report demonstrated that 4-1BB signals had immunoregulatory effects that attenuated early immune-mediated pathology and reversed the immunocompromised state observed during the later stages of disease. PMID- 22777157 TI - Mesoporous slit-structured NiO for high-performance pseudocapacitors. AB - Mesoporous slit-structured NiO materials were prepared through a simple hydrothermal route with sodium dodecyl benzene sulfonate (SDBS) as an additive. The as-prepared NiO samples presented high specific capacitance of over 1700 F g( 1) in the potential range from 0.10 to 0.56 V (vs. Hg/HgO/6 mol L(-1) KOH) at a constant current of 2 A g(-1), and good capacitance retention of ~90% after 1000 continuous charge-discharge cycles. Only the NiO electrode materials with uniform slit-structured mesopores, which were confirmed through nitrogen adsorption desorption isotherms and high-resolution transmission electron microscope, delivered excellent capacitances far beyond any previous report up to now. Pore structures (including pore shape, size, and distribution) are dominant factors in pseudocapacitor materials. PMID- 22777158 TI - A high-resolution 15,000(Rad) radiation hybrid panel for the domestic cat. AB - The current genetic and recombination maps of the cat have fewer than 3,000 markers and a resolution limit greater than 1 Mb. To complement the first generation domestic cat maps, support higher resolution mapping studies, and aid genome assembly in specific areas as well as in the whole genome, a 15,000(Rad) radiation hybrid (RH) panel for the domestic cat was generated. Fibroblasts from the female Abyssinian cat that was used to generate the cat genomic sequence were fused to a Chinese hamster cell line (A23), producing 150 hybrid lines. The clones were initially characterized using 39 short tandem repeats (STRs) and 1,536 SNP markers. The utility of whole-genome amplification in preserving and extending RH panel DNA was also tested using 10 STR markers; no significant difference in retention was observed. The resolution of the 15,000(Rad) RH panel was established by constructing framework maps across 10 different 1-Mb regions on different feline chromosomes. In these regions, 2-point analysis was used to estimate RH distances, which compared favorably with the estimation of physical distances. The study demonstrates that the 15,000(Rad) RH panel constitutes a powerful tool for constructing high-resolution maps, having an average resolution of 40.1 kb per marker across the ten 1-Mb regions. In addition, the RH panel will complement existing genomic resources for the domestic cat, aid in the accurate re-assemblies of the forthcoming cat genomic sequence, and support cross-species genomic comparisons. PMID- 22777159 TI - Colostrum of healthy mothers contains broad spectrum of secretory IgA autoantibodies. AB - PURPOSE: Human colostrum and milk provide a newborn with immunomodulatory components, ensuring protection and proper development of the immune system. Secretory IgA antibodies in colostrum represent the first line of defence against harmful substances, but their potential spectra of reactivity with autoantigens remains unclear. Here, we characterised the repertoire of natural sectretory IgA autoantibodies in colostrum of healthy mothers. METHODS: The human colostrum samples from 39 healthy mothers were analyzed for autoantibodies by indirect immunofluorescence, dot blots, immunoblots and ELISA. RESULTS: We found that there is high diversity in reactivities of colostral IgA antibodies to autoantigens among individual samples. Using tissue sections and biochips commonly used for autoimmunity testing, we found that most samples reacted with monkey ovary (79.3%), monkey pancreatic tissue (78.6%), human HEp-2 cells (69%) and monkey adrenal gland (69.0%), fewer samples reacted with monkey liver tissue (47.2%), rat stomach (42.9%), monkey testicular tissue (41.4%), monkey salivary gland (39.3%), rat kidney (32.1%) and monkey cerebellar tissue (17.9%). At the protein level, we detected reactivity of IgA with 21 out of 25 (auto) antigens. The majority of the samples reacted with the pyruvate dehydrogenase complex, E3 ubiquitin ligase, cytosolic liver antigen, promyelocytic leukemia protein and nuclear pore glycoprotein-210. Using ELISA, we found reactivity of colostral IgA antibodies against examined extractable nuclear antigens, double stranded DNA, phospholipids and neutrophil cytoplasm. CONCLUSIONS: The broad spectrum of polyreactive natural autoantibodies present in human colostrum may contribute to proper development of mucosal immune system of the breastfed infant. PMID- 22777160 TI - Isolated cationic crown ether complexes of gallium(I) and indium(I). AB - The recently reported homologous low-valent indium and gallium salts M(+)[Al(OR(F))(4)](-) (M = Ga, In; R(F) = C(CF(3))(3)) were used to extend the coordination chemistry of Ga(I) and In(I) to the isolated [18]crown-6 complexes [M([18]crown-6)(PhF)(2)](+)[Al(OR(F))(4)](-) in fluorobenzene solution (PhF = C(6)H(5)F). In contrast to known ion-paired compounds for M = In, our complexes are undisturbed and in the solid state free of contacts to the anion. A peculiar combination of very weak eta(1)- and eta(6)-coordination to the PhF-solvent was observed that allows speculation about the presence of a stereochemically active lone pair at M(I). Structure and energetics of these novel salts were rationalized on the basis of DFT calculations. PMID- 22777161 TI - Rater variables associated with ITER ratings. AB - Advocates of holistic assessment consider the ITER a more authentic way to assess performance. But this assessment format is subjective and, therefore, susceptible to rater bias. Here our objective was to study the association between rater variables and ITER ratings. In this observational study our participants were clerks at the University of Calgary and preceptors who completed online ITERs between February 2008 and July 2009. Our outcome variable was global rating on the ITER (rated 1-5), and we used a generalized estimating equation model to identify variables associated with this rating. Students were rated "above expected level" or "outstanding" on 66.4 % of 1050 online ITERs completed during the study period. Two rater variables attenuated ITER ratings: the log transformed time taken to complete the ITER [beta = -0.06, 95 % confidence interval (-0.10, -0.02), p = 0.002], and the number of ITERs that a preceptor completed over the time period of the study [beta = -0.008 (-0.02, -0.001), p = 0.02]. In this study we found evidence of leniency bias that resulted in two thirds of students being rated above expected level of performance. This leniency bias appeared to be attenuated by delay in ITER completion, and was also blunted in preceptors who rated more students. As all biases threaten the internal validity of the assessment process, further research is needed to confirm these and other sources of rater bias in ITER ratings, and to explore ways of limiting their impact. PMID- 22777162 TI - Notable increased cerebrospinal fluid levels of soluble interleukin-6 receptors in neuromyelitis optica. AB - BACKGROUND: IL-6 is a proinflammatory cytokine which is involved in the maintenance of the humoral response in various autoimmune disorders. Cerebrospinal fluid (CSF) IL-6 has shown to be increased in neuromyelitis optica (NMO). The soluble form of IL-6 receptor (sIL-6R), which links to IL-6, can activate biological responses in cells. Whether or not sIL-6R is altered in NMO has not been clarified. OBJECTIVE: To measure CSF IL-6 and sIL-6R in NMO and multiple sclerosis (MS) patients, and investigate whether IL-6 and sIL-6R have possible uses as sensitive biomarkers for diseases activity. METHODS: CSF concentrations of IL-6 and sIL-6R were measured by an ELISA in NMO (n = 22) and MS (n = 18) patients, as well as control subjects (n = 14). RESULTS: The concentration of IL-6 levels were higher in NMO compared to MS (p = 0.032) and the controls (p = 0.023). The levels of sIL-6R were also higher in NMO compared to MS (p = 0.002) and the controls (p < 0.001). CSF sIL-6R was associated with an Expanded Disability Status Scale score in NMO (p = 0.005) but not in MS (p = 0.891). In the MS subgroup, sIL-6R concentrations were associated with CSF white blood cells (p = 0.034). CONCLUSIONS: Our study revealed that CSF sIL-6R was increased in NMO patients, and correlated with clinical presentations. PMID- 22777163 TI - Retrospective investigation of gingival invaginations : Part I: Clinical findings and presentation of a coding system. AB - Many orthodontic treatments involve tooth extraction. Gingival invagination is a common side effect after orthodontic extraction space closure leading to compromised oral hygiene and the space closure being hampered. Even the long-term stability of the orthodontic treatment result may be jeopardized. The aim of this study was to identify risk factors for the development of gingival invagination and possible implications on oral health and orthodontic treatment results.A total of 30 patients presenting 101 tooth extractions and subsequent orthodontic space closure were investigated to detect the presence of gingival invagination. The time required until active space closure, the thoroughness of space closure, and probing depths mesial and distal to the extraction site in addition to age, gender and the Periodontal Screening Index were investigated. A new coding system to describe the extent of gingival invagination is introduced for the first time here.Gingival invagination developed more frequently in the lower jaw (50%) than the upper (30%). Complete penetration occurred in the upper jaw in 6% of the patients and in the lower jaw in 25%. All patients without gingival invagination revealed complete space closure, whereas only 70% in the group with gingival invagination did so. The time until initiation of space closure took significantly longer in patients with gingival invagination (7.5 +/- 1.4 months) than in patients without (3.3 +/- 0.8 months). Probing depths of the adjacent teeth were significantly greater in regions with invaginations.Thus, the time required until space closure was initiated and the extraction site are important risk factors for the development of gingival invagination. The consequences of gingival invagination are instable space closure and deeper probing depths mesial and distal to the extractions. However, no statements concerning the mid- to long term effects on oral health can be made. PMID- 22777164 TI - Correlation between the frequency of eruption disorders for first permanent molars and the occurrence of malocclusions in early mixed dentition. AB - OBJECTIVE: We analyzed the incidence of eruption disorders in 6-year molars during the first phase of mixed dentition, and then determined the risks for later dental arch development according to specific combinations of orthodontic malocclusions. We, thus, aimed to derive potential conclusions for preventative orthodontics. SUBJECTS AND METHODS: In this cross-sectional study, 8,041 kindergarten and school children with early mixed dentition were randomly selected and clinically examined. Examinations were performed in two consecutive years during the standard dental screening that school children undergo. The average age was 6.9 years. We defined an eruption of the 6-year molars as being disturbed when (1) the distal cusps had erupted further than the mesial cusps, (2) the mesial inclination of the occlusal surface revealed disturbed eruption, and (3) the 6-year molar had erupted below the second primary molar. RESULTS: Disturbed eruption of the first permanent molars was observed in 102 of these children. The upper 6-year molars were affected more often (88.5%) than the lower molars. Bilateral disturbed eruption of the upper molars was the most frequent combination of symptoms found. Although disturbed eruption was diagnosed most often in 6- and 7-year-old children, the 8-year-old children presented 20% of the eruption disorders. Moreover, 72.6% of the children with disturbed eruption presented at least one additional orthodontic malocclusion. Crowding (p <= 0.001), lateral malocclusions (p <= 0.001), and mandibular prognathism (p = 0.009) were present significantly more often in children with disturbed eruption of 6-year molars. CONCLUSION: Delayed eruption and false direction of eruption of the upper 6-year molars may-already at an early stage-raise the likelihood of problems during later dental arch development, such as crowding in the sagittal and transverse directions or Class III developments. PMID- 22777165 TI - Helicobacter pylori. PMID- 22777166 TI - The influence of simulated aging on the mechanical properties of orthodontic elastomeric chains without an intermodular link. AB - OBJECTIVE: Orthodontic elastomeric chains are a main component in orthodontic therapy with fixed vestibular or lingual appliances. The objective of this study was to investigate the influence of artificial aging on the mechanical properties of orthodontic elastomeric chains (power chains, PCs) without an intermodular link using a test setup according to DIN EN ISO 21606:2007. MATERIAL AND METHODS: In this study, 11 types of PCs supplied by seven manufacturers were investigated. Four groups with 10 specimens each were randomly generated for each type. Samples were separately mounted in a universal testing machine and extended by 300% (four times their initial length) at a crosshead rate of 100 mm/min and were held at this position for five seconds. The chain length was then reduced to three times the initial length (extension by 200%) and kept for 30 s. Then, within the control group (t = 0) and the force Fmin was recorded before extension until failure was performed and force (Fmax) and length (Lmax) at failure were determined. After prestretching, specimens of the three other groups were stored in water at 37 degrees C with its three times initial length for one day (t = 1), 14 days (t = 2), and 28 days (t = 3), respectively. The specimens were then placed in the universal testing machine and the residual force (Fmin) measured, so as to subsequently extend them until failure at Fmax and Lmax. Data were statistically analyzed by one-way analysis of variance; the level of significance was set at p = 0.05. RESULTS: Statistical analysis revealed significant differences in Fmax, Fmin, and Lmax in each group (t = 0 to t = 3) between the various manufacturers (p < 0.001). Moreover, artificial aging significantly influenced Fmax, Fmin, and Lmax (p < 0.001). CONCLUSION: The orthodontist should consider both the mechanical properties of PCs and the duration of these appliances' application when treating patients. Artificial aging had a significant influence on the parameters we determined (p <0.001). PMID- 22777167 TI - Midline correction by asymmetric reciprocal torque: a pilot study. AB - OBJECTIVE: Can we correct dental midline discrepancies by systematic torque bends on all canines and premolars without extraction and mesiodistal tooth movement? PATIENTS AND METHODS: Eight orthodontic patients (4 males, 4 emales, mean age 31 years) presented a dental midline discrepancy of 2-4 mm, moderate deviation of the chin, no skeletal asymmetry, and a horizontal orientation of the occlusal plane in the frontal aspect. On the side where the mandible was shifted medially, asymmetric torque bends moved the antagonist canine and both premolar crowns buccally, while palatal crown torque was used on the maxillary canine and premolars on the other side. Lingual crown torque corrected the medially shifted canine and premolars in the mandibular dental arch, and buccal crown torque the laterally shifted lower canine and premolars. RESULTS: On average, torque effects altered the canine guidance by 6.5 +/- 4.7 degrees , the first premolar guidance by 7 +/- 4.1 degrees , and the second premolar guidance by 6.3 +/- 3.7 degrees . Correction of the dental midline shift averaged 1.6 +/- 0.8 mm after the torque, and eliminated the midline discrepancy completely (n = 2) or partly (n = 6). CONCLUSION: In this pilot study, asymmetric reciprocal torque represented a treatment option for midline corrections of approximately 2-4 mm and improvement in the chin position without mesiodistal tooth movement or extraction. PMID- 22777169 TI - What's new on the dental scene?: browsing through the dental literature. PMID- 22777168 TI - Juvenile idiopathic arthritis-and now?: a systematic literature review of changes in craniofacial morphology. AB - AIM: To conduct a systematic literature review on the impact of juvenile idiopathic arthritis (JIA) on craniofacial morphology. MATERIALS AND METHODS: Several electronic databases (PubMed, Medpilot, Web of Science, DIMDI) were systematically searched for studies that were published up to and including May 2011. In addition, a manual search of the orthodontic and rheumatologic literature was conducted, and reference lists of the selected articles were checked for relevant publications. The identified articles were independently assessed by two investigators and selected according to a three-step process (title/abstract/full text). RESULTS: After completion of the selection procedure, 19 articles were identified possessing great heterogeneity. In most of them, no differentiated analysis of the various JIA subtypes was performed, and type specific analyses according to mandibular joint effects were seldom. Additional factors such as patient age, disease duration, medication, previous orthodontic treatment as well as the inclusion of a control group were also highly inhomogeneous, which made a meta-analysis of the data impossible. Nevertheless, it appears as if JIA patients tend to develop a hyperdivergent vertical jaw base relationship and a skeletal Class II pattern. CONCLUSION: Due to the heterogeneous patient samples, it is currently not possible to draw a differentiated conclusion on the influence of various types of JIA on craniofacial morphology. PMID- 22777170 TI - Use of a virtual reality simulator to improve percutaneous renal access skills: a prospective study in urology trainees. AB - OBJECTIVES: This study aims to assess the impact of a virtual reality trainer in improving percutaneous renal access skills of urological trainees. METHODS: A total of 36 urology trainees participated in this prospective study. Initially, they were taken through the exercise of gaining access to the lower pole calyceal system and introducing a guidewire down the ureter. Trainees' performance was then assessed by virtual reality-derived parameters of the simulator at baseline and after 2 h of training. RESULTS: Participants who underwent training with the simulator demonstrated significant improvement in several parameters compared to their baseline performance. There was a statistically significant correlation between total time to perform the procedure and time of radiation exposure, radiation dose and correct calyx puncture (p < 0.01). Trainees needed a mean of 15.8 min from skin puncture to correct guidewire placement into the pelvicalyceal system before and 6.49 min following training. CONCLUSIONS: We found percutaneous renal access skills of trainees improve significantly on a number of parameters as a result of training on the PERC Mentor TM VR simulator. Such simulated training has the potential to decrease the risks and complications associated with the early stages of the learning curve when training for percutaneous renal access in patients. PMID- 22777171 TI - Placenta proteome analysis from Down syndrome pregnancies for biomarker discovery. AB - Down syndrome is one of the most frequent chromosomal disorders, with a prevalence of approximately 1/500 to 1/800, depending on the maternal age distribution of the pregnant population. However, few reliable protein biomarkers have been used in the diagnosis of this disease. Recent progress in quantitative proteomics has offered opportunities to discover biomarkers for tracking the progression and for understanding the molecular mechanisms of Down syndrome. In the present study, placental samples were analyzed by fluorescence two dimensional differential gel electrophoresis (2D-DIGE) and differentially expressed proteins were identified by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). In total, 101 proteins have been firmly identified representing 80 unique gene products. These proteins mainly function in cytoskeleton structure and regulation (such as vimentin and Profilin 1). Additionally, our quantitative proteomics approach has identified numerous previously reported Down syndrome markers, such as myelin protein. Here we present several Down syndrome biomarkers including galectin-1, ataxin-3 and sprouty-related EVH1 domain-containing protein 2 (SPRED2), which have not been reported elsewhere and may be associated with the progression and development of the disease. In summary, we report a comprehensive placenta-based proteomics approach for the identification of potential biomarkers for Down syndrome, in which serum amyloid P-component (APCS) and ataxin-3 have been shown to be up regulated in the maternal peripheral plasma of Down syndrome cases. The potential of utilizing these markers for the prognosis and screening of Down syndrome warrants further investigation. PMID- 22777172 TI - Colonoscopy: New device for colon cleansing. PMID- 22777175 TI - Cardiac rehabilitation: call to action for healthcare providers. PMID- 22777173 TI - Infantile hypertrophic pyloric stenosis--genetics and syndromes. AB - Infantile hypertrophic pyloric stenosis (IHPS) is a common condition in neonates that is characterized by an acquired narrowing of the pylorus. The aetiology of isolated IHPS is still largely unknown. Classic genetic studies have demonstrated an increased risk in families of affected infants. Several genetic studies in groups of individuals with isolated IHPS have identified chromosomal regions linked to the condition; however, these associations could usually not be confirmed in subsequent cohorts, suggesting considerable genetic heterogeneity. IHPS is associated with many clinical syndromes that have known causative mutations. Patients with syndromes associated with IHPS can be considered as having an extreme phenotype of IHPS and studying these patients will be instrumental in finding causes of isolated IHPS. Possible pathways in syndromic IHPS include: (neuro)muscular disorders; connective tissue disorders; metabolic disorders; intracellular signalling pathway disturbances; intercellular communication disturbances; ciliopathies; DNA-repair disturbances; transcription regulation disorders; MAPK-pathway disturbances; lymphatic abnormalities; and environmental factors. Future research should focus on linkage analysis and next generation molecular techniques in well-defined families with multiple affected members. Studies will have an increased chance of success if detailed phenotyping is applied and if knowledge about the various possible causative pathways is used in evaluating results. PMID- 22777176 TI - Cardiac rehabilitation attendance and outcomes in coronary artery disease patients. AB - BACKGROUND: Cardiac rehabilitation (CR) is an efficacious yet underused treatment for patients with coronary artery disease. The objective of this study was to determine the association between CR completion and mortality and resource use. METHODS AND RESULTS: We conducted a prospective cohort study of 5886 subjects (20.8% female; mean age, 60.6 years) who had undergone angiography and were referred for CR in Calgary, AB, Canada, between 1996 and 2009. Outcomes of interest included freedom from emergency room visits, hospitalization, and survival in CR completers versus noncompleters, adjusted for clinical covariates, treatment strategy, and coronary anatomy. Hazard ratios for events for CR completers versus noncompleters were also constructed. A propensity model was used to match completers to noncompleters on baseline characteristics, and each outcome was compared between propensity-matched groups. Of the subjects referred for CR, 2900 (49.3%) completed the program, and an additional 554 subjects started but did not complete CR. CR completion was associated with a lower risk of death, with an adjusted hazard ratio of 0.59 (95% confidence interval, 0.49 0.70). CR completion was also associated with a decreased risk of all-cause hospitalization (adjusted hazard ratio, 0.77; 95% confidence interval, 0.71-0.84) and cardiac hospitalization (adjusted hazard ratio, 0.68; 95% confidence interval, 0.55-0.83) but not with emergency room visits. Propensity-matched analysis demonstrated a persistent association between CR completion and reduced mortality. CONCLUSIONS: Among those coronary artery disease patients referred, CR completion is associated with improved survival and decreased hospitalization. There is a need to explore reasons for nonattendance and to test interventions to improve attendance after referral. PMID- 22777177 TI - Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the American Heart Association and the American Diabetes Association. PMID- 22777179 TI - Population dynamics of DENV-1 genotype V in Brazil is characterized by co circulation and strain/lineage replacement. AB - Following successive outbreaks of dengue fever caused predominantly by dengue virus (DENV) 2 and 3, DENV-1 is now the primary serotype circulating in Brazil. We sequenced and analyzed Brazilian DENV-1 genomes and found that all isolates belong to genotype V and are subdivided into three lineages, which were introduced during four different events. The first introduction occurred in 1984 85, the second in 1997-99, and the third and fourth occurred from 2004 to 2007. These events were associated with an increase in genetic diversity but not with positive selection. Moreover, a potential new recombinant strain derived from two distinct lineages was detected. We demonstrate that the dynamics of DENV-1 in Brazil is characterized by introduction, movement, local evolution, and lineage replacement. This study strengthens the relevance of genotype surveillance in order to identify, trace, and control virus populations circulating in Brazil and Latin America. PMID- 22777178 TI - Synthesis and biological evaluation of 1,4-naphthoquinones and quinoline-5,8 diones as antimalarial and schistosomicidal agents. AB - Improving the solubility of polysubstituted 1,4-naphthoquinone derivatives was achieved by introducing nitrogen in two different positions of the naphthoquinone core, at C-5 and at C-8 of menadione through a two-step, straightforward synthesis based on the regioselective hetero-Diels-Alder reaction. The antimalarial and the antischistosomal activities of these polysubstituted aza-1,4 naphthoquinone derivatives were evaluated and led to the selection of distinct compounds for antimalarial versus antischistosomal action. The Ag(II)-assisted oxidative radical decarboxylation of the phenyl acetic acids using AgNO(3) and ammonium peroxodisulfate was modified to generate the 3-picolinyl-menadione with improved pharmacokinetic parameters, high antimalarial effects and capacity to inhibit the formation of beta-hematin. PMID- 22777180 TI - A novel cassava-infecting begomovirus from Madagascar: cassava mosaic Madagascar virus. AB - Cassava mosaic geminiviruses (CMGs) are implicated in cassava mosaic disease (CMD), the main constraint to cassava production in Africa. Here, we report the complete nucleotide sequences of the DNA-A and DNA-B of a newly characterized CMG found infecting cassava in Madagascar, for which we propose the tentative name cassava mosaic Madagascar virus. With the exception of two recombinant regions that resembled a CMG, we determined that the non-recombinant part of the DNA-A component is distantly related to the other CMGs. Whereas the DNA-B component possesses one recombinant region originating from an unidentified virus, the rest of the genome was seen to be closely related to members of the species East African cassava mosaic Zanzibar virus (EACMZV). Phylogenetic analysis based on complete genome sequences demonstrated that DNA-A and DNA-B components are outliers related to the clade of EACMV-like viruses and that DNA-A is related to the monopartite tomato leaf curl begomoviruses described in islands in the south west Indian Ocean. PMID- 22777181 TI - Molecular analysis of the mutational effects of Thai street rabies virus with increased virulence in mice after passages in the BHK cell line. AB - QS-BHK-P7, street rabies virus, after passages in the BHK cell line, had an in vitro phenotype that distinguished it from its parental virus. Both viruses caused lethal infection in mice by central nervous system inoculation; however, only QS-BHK-P7 killed mice by the intramuscular route. We found four mutations, S23R and H424P in ectodomain of the glycoprotein (G), I1711 V in the polymerase genes, and another at the non-coding region between the phosphoprotein and matrix protein genes of QS-BHK-P7. None of the mutations in the G gene occurred in previously reported pathogenic determinants. The roles of mutations in particular non-coding regions remain to be elucidated. PMID- 22777182 TI - Stent-assisted coiling treatment of pediatric traumatic pseudoaneurysm resulting from tumor surgery. AB - BACKGROUND: Traumatic intracranial pseudoaneurysms in children are typically the result of blunt or penetrating head injury. There are isolated reports of pseudoaneurysm as the result of intracranial aneurysm surgery in both adults and children. Treatment of these lesions, both surgically and endovascularly, can be complicated due to the known variability of arterial wall thickness in traumatic pseudoaneurysms. CASE REPORT: We describe a child who underwent successful craniopharyngioma resection following staged surgical procedures. Follow-up imaging 8 months after the operation demonstrated an enlarging pseudoaneurysm of the left supraclinoid carotid artery. The lesion was successfully treated with stenting of the vessel and coil placement between the stent and the aneurysmal segment of the artery. Follow-up angiographic imaging 6 months later revealed complete obliteration of the aneurysm and normalization of the carotid artery lumen. CONCLUSION: To our knowledge, this is the first report of a pseudoaneurysm secondary to a surgical intervention in childhood that was treated with stent assisted coiling. This strategy of vascular reconstruction is increasingly used in adults and appears safe to implement in the pediatric population. However, the long-term outcomes and the value of using an antiplatelet regimen in this young population are still to be determined. PMID- 22777183 TI - Throughput and delay analysis of IEEE 802.15.6-based CSMA/CA protocol. AB - The IEEE 802.15.6 is a new communication standard on Wireless Body Area Network (WBAN) that focuses on a variety of medical, Consumer Electronics (CE) and entertainment applications. In this paper, the throughput and delay performance of the IEEE 802.15.6 is presented. Numerical formulas are derived to determine the maximum throughput and minimum delay limits of the IEEE 802.15.6 for an ideal channel with no transmission errors. These limits are derived for different frequency bands and data rates. Our analysis is validated by extensive simulations using a custom C+ + simulator. Based on analytical and simulation results, useful conclusions are derived for network provisioning and packet size optimization for different applications. PMID- 22777186 TI - Formation of M4Se4 cuboids (M = As, Sb, Bi) via secondary pnictogen-chalcogen interactions in the co-crystals MX3.Se=P(p-FC6)H4)3 (M = As, X = Br; M = Sb, X = Cl; M = Bi, X = Cl, Br). AB - The reactions of the group 15 trihalides, MX(3) (M = As, Sb, Bi; X = Cl, Br), with the phosphine selenide SeP(p-FC(6)H(4))(3) result in the formation of co crystals of formula MX(3).SeP(p-FC(6)H(4))(3). No reaction was observed with MI(3) (M = As, Sb, Bi). The structures of MX(3).SeP(p-FC(6)H(4))(3) (M = As, X = Br 2; M = Sb, X = Cl 3; M = Bi, X = Cl 5; M = Bi, X = Br 6) have been established, and are isomorphous, crystallising in the cubic I23 space group. All the structures feature a primary MX(3) unit, which has three weak secondary MSe interactions to SeP(p-FC(6)H(4))(3) molecules. However, each of these SeP(p FC(6)H(4))(3) molecules bridges three MX(3) molecules, resulting in the generation of an M(4)Se(4) (M = As, Sb, Bi) distorted cuboid linked by the pnictogen-chalcogen interactions. Four opposing corners of the cuboid are occupied by the M atom (M = As, Sb, Bi) of an MX(3) pyramid, and the other four by the selenium atom of the phosphine selenide. PMID- 22777185 TI - Aquaporin-4 in the heart: expression, regulation and functional role in ischemia. AB - Aquaporins (AQPs) are channel-forming membrane proteins highly permeable to water. AQP4 is found in mammalian hearts; however, its expression sites, regulation and function are largely unknown. The aim was to investigate cardiac AQP4 expression in humans and mice, its regulation by ischemia and hypoxia, and in particular its role in cardiac ischemic injury using AQP4 knockout (KO) mice. Comparable levels of AQP4 were detected by Western blot and qPCR in biopsies from human donor hearts and wild type C57Bl6 mouse hearts. In mice, AQP4 was expressed on cardiomyocyte plasmalemma (qPCR, Western blot, immunogold), and its mRNA decreased following ischemia/reperfusion (isolated hearts, p = 0.02) and after normobaric hypoxia in vivo (oxygen fraction 10 % for 1 week, p < 0.001). Isolated hearts from AQP4 KO mice undergoing global ischemia and reperfusion had reduced infarct size (p = 0.05) and attenuated left ventricular end-diastolic pressure during reperfusion (p = 0.04). Infarct size was also reduced in AQP4 KO mice 24 h after left coronary artery ligation in vivo (p = 0.036). AQP4 KO hearts had no compensatory change in AQP1 protein expression. AQP4 KO cardiomyocytes were partially resisted to hypoosmotic stress in the presence of hypercontracture. AQP4 is expressed in human and mouse hearts, in the latter confined to the cardiomyocyte plasmalemma. AQP4 mRNA expression is downregulated by hypoxia and ischemia. Deletion of AQP4 is protective in acute myocardial ischemia reperfusion, and this molecule might be a future target in the treatment of acute myocardial infarction. PMID- 22777187 TI - Cytotoxic effect of eudesmanolides isolated from flowers of Tanacetum vulgare ssp. siculum. AB - A phytochemical analysis of the dichloromethane extract from the flowers of a subspecies of Tanacetum vulgare growing in Sicily was carried out. Five known sesquiterpene lactones with the eudesmane skeleton have been isolated and the cytotoxic activity of these compounds was tested in vitro on A549 (human lung carcinoma epithelial-like) and V79379A (Chinese hamster lung fibroblast-like) cells using the tetrazolium salt reduction (MTT) assay. All of tested compounds induced high time- and concentration-dependent cytotoxic effects. PMID- 22777184 TI - Constitutive phosphorylation of inhibitor-1 at Ser67 and Thr75 depresses calcium cycling in cardiomyocytes and leads to remodeling upon aging. AB - The activity of protein phosphatase-1 (PP1) inhibitor-1 (I-1) is antithetically modulated by the cAMP-protein kinase A (PKA) and Ca(2+)-protein kinase C (PKC) signaling axes. beta-adrenergic (beta-AR) stimulation results in PKA phosphorylation of I-1 at threonine 35 (Thr35) and depressed PP1 activity, while PKC phosphorylation at serine 67 (Ser67) and/or Thr75 increases PP1 activity. In heart failure, pThr35 is decreased while pSer67 and pThr75 are elevated. However, the role of Ser67/Thr75 phosphorylation in vivo and its effects on Ca(2+)-cycling are not known. Thus, our aim was to investigate the functional significance of Ser67 and Thr75 phosphorylation in intact hearts. We generated transgenic mice (TG) with cardiac-specific overexpression of constitutively phosphorylated I-1 at Ser67 and Thr75 (S67D/T75D) and evaluated cardiac function. The S67D/T75D cardiomyocytes exhibited significantly depressed Ca(2+)-kinetics and contractile parameters, compared with wild-type (WT) cells. The decreased Ca(2+)-cycling was associated with a 27 % increase in PP1 activity, no alterations in PP2 activity and impaired phosphorylation of myosin-binding protein-C (MyBPC). Upon aging, there was cardiac remodeling associated with increases in systolic and diastolic left ventricular internal diameter dimensions (at 16 months), compared with WTs. The results indicate that phosphorylation of I-1 at Ser67 and Thr75 is associated with increased PP1 activity and depressed cardiomyocyte Ca(2+)-cycling, which manifests in geometrical alterations over the long term. Thus, hyperphosphorylation of these sites in failing hearts may contribute to deteriorative remodeling. PMID- 22777188 TI - Terpenes as green solvents for extraction of oil from microalgae. AB - Herein is described a green and original alternative procedure for the extraction of oil from microalgae. Extractions were carried out using terpenes obtained from renewable feedstocks as alternative solvents instead of hazardous petroleum solvents such as n-hexane. The described method is achieved in two steps using Soxhlet extraction followed by the elimination of the solvent from the medium using Clevenger distillation in the second step. Oils extracted from microalgae were compared in terms of qualitative and quantitative determination. No significant difference was obtained between each extract, allowing us to conclude that the proposed method is green, clean and efficient. PMID- 22777189 TI - An alternative synthesis of 3',4'-diaminoflavones to evaluate their antioxidant ability and cell apoptosis of zebrafish larvae. AB - We described herein a concise synthesis of 3',4'-diaminoflavone 10. This new, three-step synthetic approach is more efficient than the conventional seven-step synthetic method. The route is shortened significantly by introducing the amino moieties early and eliminating the need for nitro group reduction. The other two analogues, 5,7-dihydroxy-3',4'-diaminoflavone 11 and 5,7-dimethoxy-3',4' diaminoflavone 12, were also synthesized similarly. The above three compounds, along with flavone, were evaluated for their antioxidant and UVB-protection abilities on zebrafish larvae. The data showed that compound 10 exhibited the best result, with -102.3% of ROS-scavenging rate. PMID- 22777190 TI - Synthesis and antibacterial evaluation of a new series of N-Alkyl-2-alkynyl/(E) alkenyl-4-(1H)-quinolones. AB - To gain further insight into the structural requirements of the aliphatic group at position 2 for their antimycobacterial activity, some N-alkyl-4-(1H) quinolones bearing position 2 alkynyls with various chain length and triple bond positions were prepared and tested for in vitro antibacterial activity against rapidly-growing strains of mycobacteria, the vaccine strain Mycobacterium bovis BCG, and methicillin-resistant Staphylococcus aureus strains, EMRSA-15 and -16. The compounds were also evaluated for inhibition of ATP-dependent MurE ligase of Mycobacterium tuberculosis. The lowest MIC value of 0.5 mg/L (1.2-1.5 uM) was found against M. fortuitum and M. smegmatis. These compounds displayed no or only weak toxicity to the human lung fibroblast cell line MRC-5 at 100 uM concentration. The quinolone derivatives exhibited pronounced activity against the epidemic MRSA strains (EMRSA-15 and -16) with MIC values of 2-128 mg/L (5.3 364.7 uM), and M. bovis BCG with an MIC value of 25 mg/L (66.0-77.4 uM). In addition, the compounds inhibited the MurE ligase of M. tuberculosis with moderate to weak activity showing IC50 values of 200-774 uM. The increased selectivity towards mycobacterial bacilli with reference to MRC-5 cells observed for 2-alkynyl quinolones compared to their corresponding 2-alkenyl analogues serves to highlight the mycobacterial specific effect of the triple bond. Exploration of a terminal bromine atom at the side chain of N-alkyl-2-(E)-alkenyl 4-(1H)-quinolones showed improved antimycobacterial activity whereas a cyclopropyl residue at N-1 was suggested to be detrimental to antibacterial activity. PMID- 22777191 TI - The "funny" current (I(f)) inhibition by ivabradine at membrane potentials encompassing spontaneous depolarization in pacemaker cells. AB - Recent clinical trials have shown that ivabradine (IVA), a drug that inhibits the funny current (I(f)) in isolated sinoatrial nodal cells (SANC), decreases heart rate and reduces morbidity and mortality in patients with cardiovascular diseases. While IVA inhibits I(f), this effect has been reported at essentially unphysiological voltages, i.e., those more negative than the spontaneous diastolic depolarization (DD) between action potentials (APs). We tested the relative potency of IVA to block I(f) over a wide range of membrane potentials, including those that encompass DD governing to the SANC spontaneous firing rate. A clinically relevant IVA concentration of 3 MUM to single, isolated rabbit SANC slowed the spontaneous AP firing rate by 15%. During voltage clamp the maximal I(f) was 18 +/- 3 pA/pF (at -120 mV) and the maximal I(f) reduction by IVA was 60 +/- 8% observed at -92 +/- 4 mV. At the maximal diastolic depolarization (~-60 mV) I(f) amplitude was only -2.9 +/- 0.4 pA/pF, and was reduced by only 41 +/- 6% by IVA. Thus, I(f) amplitude and its inhibition by IVA at physiologically relevant membrane potentials are substantially less than that at unphysiological (hyperpolarized) membrane potentials. This novel finding more accurately describes how IVA affects SANC function and is of direct relevance to numerical modeling of SANC automaticity. PMID- 22777192 TI - A comparison of the antihypertensive and anti-inflammatory effects of aliskiren and ramipril add-on therapy in peritoneal dialysis patients--a pilot open label study. AB - Most hypertensive dialysis patients are currently treated with angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). Aliskiren, the direct renin inhibitor, has not been specifically studied in peritoneal dialysis patients. The aim of the study was to compare hypotensive effects of aliskiren and ramipril and their influence on serum potassium and inflammatory parameters in hypertensive peritoneal dialysis patients. Eighteen hypertensive patients on chronic peritoneal dialysis were enrolled in an open label comparative fixed-order study. The patients had been off RAAS blocking drugs for >=4 weeks prior to an inclusion. At each of 3 study visits (baseline and after each of the treatment periods) blood pressure, serum lipids, potassium, renin, aldosterone, C-reactive protein (CRP) and monocyte chemotactic protein-1 (MCP-1) were measured. After the baseline visit aliskiren was started (150 mg/d) and after 12 weeks replaced with ramipril (5 mg/d) for the next 12 weeks. Blood pressure was 142/88+/-15/11 mmHg at baseline, 137/84+/-10/8 mmHg after aliskiren (ns) and 126/81+/-11/7 mmHg after ramipril (p<0.05 vs baseline and aliskiren). No incidents of hyperkalemia were observed. Plasma renin concentration increased significantly during aliskiren treatment compared to ramipril (227,6+/-844 vs. 58,3+/-765 pg/mL). CRP was similar after both therapies (8,8+/-34 vs. 8,4+/-32 ug/mL) but MCP-1 concentration was significantly lower after aliskiren than after ramipril (294,0+/-172,6 vs. 358,9+/-183,3 pg/mL). Aliskiren 150 mg/day decreases blood pressure less effectively than ramipril 5 mg/day in peritoneal dialysis patients. It does not influence serum potassium. The decrease of MCP-1 concentration after aliskiren treatment may provide an indirect evidence for its blood pressure independent cardioprotective and anti-inflammatory effects. PMID- 22777193 TI - Value of imaging lenticulostriate arteries before middle cerebral artery stenting for the prevention of perforator stroke. AB - INTRODUCTION: In this study, we investigated whether pre-procedural imaging of LSAs would potentially be helpful for preventing LSAs from being covered. METHODS: We retrospectively evaluated the LSAs of 15 consecutive patients who underwent revascularization for symptomatic middle cerebral artery (MCA) stenosis. All patients underwent two- (2D) and three-dimensional (3D) digital subtraction angiography. RESULTS: We found that 46.7 (7/15), 40 (6/15), and 13.3 % (2/15) of patients had stenotic lesions in the proximal, middle, and distal third of the M1 segment, respectively. There was a total of 32 LSAs that originated from the lesioned MCAs. Seven (21.9 %), 10 (31.3 %), 11 (34.4 %), and 4 (12.5 %) LSAs originated from the proximal third of the M1 segment, middle third of the M1 segment, distal third of the M1 segment, and starting segment of the superior M2 segment, respectively. Sixteen (76.2 %) of 22 LSAs in 13 patients were covered by stents. It would have been possible to avoid covering 43.8 % (7/16) of these LSAs with stents if they had been evaluated before stenting, and the stents had been accurately deployed. Among 16 LSAs which were covered by stent, only one (6.25 %) was occluded after coverage. CONCLUSION: Our data suggest that evaluation of LSAs during MCA stenting would be potentially helpful for preventing LSAs from being covered and subsequently occluded by stents. PMID- 22777194 TI - Bochdalek's flower basket: applied neuroimaging morphometry and variants of choroid plexus in the cerebellopontine angles. AB - INTRODUCTION: Protrusions of fourth ventricular choroid plexus through the foramina of Luschka are called 'Bochdalek's flower basket' (BochFB). The bulbous terminal expansions (cornucopiae) extend into the cerebellopontine angle (CPA) cisterns. We studied and reviewed the normal imaging anatomy, morphometry and anatomical variants of BochFB. METHODS: We retrospectively analysed normal brain imaging findings on axial pre- and post-contrast CT scans and enhanced axial T1 weighted MRIs of 200 patients. We assessed BochFB for: (a) calcification, (b) lateral extension, (c) enhancement pattern, (d) cornucopiae shape, (e) symmetry and (f) proximity to tortuous vertebral arteries and morphometry of cornucopiae size and length of BochFB limbs. RESULTS: BochFB calcification was found in 38 % of patients aged over 51 years. Lateral extension of BochFB into the CPA cistern was prominent in 75 % on CT and 96 % on MRI. The mean length of these extensions was 23.6 mm. BochFB enhanced strongly in 47 % on CT and 66 % on MRI. The BochFB cornucopiae were bulbous in 51 % on CT and 54 % on MRI. The mean width of bulbous cornucopiae was 3.5 mm. Bilateral BochFB symmetry was found in 71 % on CT and 80 % on MRI. Six to 8 % of tortuous left vertebral arteries were close to BochFB. CONCLUSION: The cornucopiae are particularly well demonstrated on post-contrast MRI. However several sources of error in image interpretation may arise when imaging the normal BochFB on routine head CT and MRI. Difficulties in analysis arise especially on CT because of physiologic calcification, asymmetry, and the bulbous cornucopiae being mistaken for aneurysms. PMID- 22777195 TI - The evolution of marsupial and monotreme chromosomes. AB - Marsupial and monotreme mammals fill an important gap in vertebrate phylogeny between reptile-mammal divergence 310 million years ago (mya) and the eutherian (placental) mammal radiation 105 mya. They possess many unique features including their distinctive chromosomes, which in marsupials are typically very large and well conserved between species. In contrast, monotreme genomes are divided into several large chromosomes and many smaller chromosomes, with a complicated sex chromosome system that forms a translocation chain in male meiosis. The application of molecular cytogenetic techniques has greatly advanced our understanding of the evolution of marsupial chromosomes and allowed the reconstruction of the ancestral marsupial karyotype. Chromosome painting and gene mapping have played a vital role in piecing together the puzzle of monotreme karyotypes, particularly their complicated sex chromosome system. Here, we discuss the significant insight into karyotype evolution afforded by the combination of recently sequenced marsupial and monotreme genomes with cytogenetic analysis, which has provided a greater understanding of the events that have shaped not only marsupial and monotreme genomes, but the genomes of all mammals. PMID- 22777196 TI - Current world literature. PMID- 22777202 TI - Transplantation: All for one and one for all--alloimmunization and polyreactivity. PMID- 22777204 TI - [Chronic obstructive pulmonary disease, periorbital and subconjunctival swelling]. AB - A 70-year-old man with a history of chronic obstructive pulmonary disease (COPD) and dilative cardiomyopathy was referred due to acute dyspnea and chest pain. After spontaneous pneumothorax was confirmed by chest radiography, a chest tube was inserted into the right side. Persistent air bubbles escaping through the water seal of the drainage in synchrony with respiration indicated a bronchopleural fistula. A physical examination revealed orbital and subconjunctival emphysemas. Skull and chest computed tomography (CT) scans showed further massive cervical, thoracic and pulmonary subcutaneous emphysemas which are increased subcutaneous amounts of gas which can disperse along the fasciae. Cardinal sign is the sensation of air under the skin known as subcutaneous crepitation (similiar to touching rice crispies). Conditions causing subcutaneous emphysemas are trauma, medical treatment and intracutaneous gas production by bacteria. In this case, large amounts of air leaked out of the pleural space through the incision made for the chest tube into the subcutaneous tissue, mediastinum and retroperitoneum causing subcutaneous emphysemas. From there, ascending air spread along the fascial planes of the mediastinum and cervical area through the inferior orbital fissure to the orbits and eyelids causing orbital and subconjunctival emphysemas. On the basis of the progressive emphysemas and persistent pneumothorax, a second chest tube was inserted. Subsequently, the signs and symptoms disappeared completely. PMID- 22777203 TI - Protecting the peritoneal membrane: factors beyond peritoneal dialysis solutions. AB - Functional deterioration of the peritoneal membrane in patients on peritoneal dialysis has been described as being the result of a combination of neoangiogenesis and fibrosis. Glucose, glucose degradation products, and the unphysiological pH of the dialysate solution contribute to these changes. Although newer solutions clearly perform better in terms of their biocompatibility in an in vitro setting and in animal models, the benefit of such solutions over older solutions in the clinical setting is so far unproven. The difficulties in showing a benefit of the newer, more biocompatible solutions in the clinical setting can be explained by the fact that other factors also affect the properties of the peritoneal membrane. These factors are often neglected in clinical studies, which results in unnoticed differences in case-mix and blurs the potential impact of the novel solutions. However, many of these factors are modifiable, and attention should be paid to them in clinical practice to maintain the integrity of the peritoneal membrane. This Review focuses on factors that potentially influence the integrity of the peritoneal membrane, other than those associated with the peritoneal dialysis fluid itself. PMID- 22777205 TI - Post-transcriptional Boolean computation by combining aptazymes controlling mRNA translation initiation and tRNA activation. AB - In cellular systems environmental and metabolic signals are integrated for the conditional control of gene expression. On the other hand, artificial manipulation of gene expression is of high interest for metabolic and genetic engineering. Especially the reprogramming of gene expression patterns to orchestrate cellular responses in a predictable fashion is considered to be of great importance. Here we introduce a highly modular RNA-based system for performing Boolean logic computation at a post-transcriptional level in Escherichia coli. We have previously shown that artificial riboswitches can be constructed by utilizing ligand-dependent Hammerhead ribozymes (aptazymes). Employing RNA self-cleavage as the expression platform-mechanism of an artificial riboswitch has the advantage that it can be applied to control several classes of RNAs such as mRNAs, tRNAs, and rRNAs. Due to the highly modular and orthogonal nature of these switches it is possible to combine aptazyme regulation of activating a suppressor tRNA with the regulation of mRNA translation initiation. The different RNA classes can be controlled individually by using distinct aptamers for individual RNA switches. Boolean logic devices are assembled by combining such switches in order to act on the expression of a single mRNA. In order to demonstrate the high modularity, a series of two-input Boolean logic operators were constructed. For this purpose, we expanded our aptazyme toolbox with switches comprising novel behaviours with respect to the small molecule triggers thiamine pyrophosphate (TPP) and theophylline. Then, individual switches were combined to yield AND, NOR, and ANDNOT gates. This study demonstrates that post-transcriptional aptazyme-based switches represent versatile tools for engineering advanced genetic devices and circuits without the need for regulatory protein cofactors. PMID- 22777206 TI - Is grip strength associated with length of stay in hospitalised older patients admitted for rehabilitation? Findings from the Southampton grip strength study. AB - BACKGROUND: identification of patients at risk of prolonged hospital stay allows staff to target interventions, provide informed prognosis and manage healthcare resources. Admission grip strength is associated with discharge outcomes in acute hospital settings. OBJECTIVE: to explore the relationship between grip strength and length of stay in older rehabilitation in-patients. DESIGN: single-centre prospective cohort study. SETTING: community hospital rehabilitation ward. SUBJECTS: one hundred and ten patients aged 70 years and over. METHODS: data on age, height, weight, body mass index (BMI), co-morbidities, medication, residence, grip strength, physical function, cognitive function, frailty, falls, discharge destination and length of stay were recorded. RESULTS: higher grip strength was associated with reduced length of stay, characterised by an increased likelihood of discharge to usual residence among male rehabilitation in patients (hazard ratio 1.09 (95% confidence interval 1.01, 1.17) per kilo increase in grip strength, P = 0.02) after adjustment for age and size. CONCLUSIONS: this is the first prospective study to show that stronger grip strength, particularly among male in-patients, is associated with a shorter length of stay in a rehabilitation ward. This is important because it demonstrates that grip strength can be discriminatory among frailer people. Further research into the clinical applications of grip strength measurement in rehabilitation settings is needed. PMID- 22777207 TI - Moving knowledge into action: developing the rapid synthesis and translation process within the interactive systems framework. AB - The Interactive Systems Framework (ISF) for Dissemination and Implementation presents an overall framework for translating knowledge into action. Each of its three systems requires further clarification and explanation to truly understand how to conduct this work. This article describes the development and initial application of the Rapid Synthesis and Translation Process (RSTP) using the exchange model of knowledge transfer in the context of one of the ISF systems: the Prevention Synthesis and Translation System (see [special issue "introduction" article] for a translation of the Wandersman et al. (Am J Community Psychol 41:3-4, 2008) article using the RSTP). This six-step process, which was developed by and for the Division of Violence Prevention at the Centers for Disease Control and Prevention in collaboration with partners, serves as an example of how a federal agency can expedite the transfer of research knowledge to practitioners to prevent violence. While the RSTP itself represents one of the possible functions in the Prevention Synthesis and Translation System, the resulting products affect both prevention support and prevention delivery as well. Examples of how practitioner and researcher feedback were incorporated into the Rapid Synthesis and Translation Process are discussed. PMID- 22777210 TI - Blister-like supraclinoid internal carotid artery pseudoaneurysm in a 15-year-old male: case report and review of the literature. AB - With an incidence of less than 1-3 per million, pediatric aneurysms are rare clinical entities. A traumatic etiology is implicated in a large proportion of these cases, leading to the formation of both 'false' and 'true' aneurysms. These occur most often in the distal circulation, but have also been described in the supraclinoid distal internal carotid artery (ICA). Blood blister aneurysms are also found in this location; however, they have not been described in the pediatric population. We report the case of a 15-year-old male who presented following cranial trauma with diffuse basal subarachnoid hemorrhage and limited additional intracranial pathology. Computed tomography angiography demonstrated a small, 2-mm blister-like aneurysm arising from the dorsal surface of the left supraclinoid ICA at a non-branching site. Despite early endovascular treatment with Guglielmi detachable coils, the lesion continued to grow over subsequent studies, necessitating open surgical clipping. At the time of surgery, gross pathology of the native ICA was observed, raising the possibility of a preexisting blood-blister aneurysm. We review the epidemiology, pathophysiology and diagnostic considerations of these lesions. The endovascular and surgical management of these complex non-branching supraclinoid ICA aneurysms is also discussed. PMID- 22777209 TI - Effect of polysaccharides extract of rhizoma atractylodis macrocephalae on thymus, spleen and cardiac indexes, caspase-3 activity ratio, Smac/DIABLO and HtrA2/Omi protein and mRNA expression levels in aged rats. AB - This study was designed to determine the possible protective effect of polysaccharides extract of rhizoma atractylodis macrocephalae on heart function in aged rats. Polysaccharides extract of rhizoma atractylodis macrocephalae was administered to aged rats. Results showed that thymus, spleen and cardiac indexs were significantly increased, whereas caspase-3 activity ratio, Smac/DIABLO and HtrA2/Omi protein expression, Smac/DIABLO and HtrA2/Omi mRNA expression levels were markedly reduced. It can be concluded that polysaccharides extract of rhizoma atractylodis macrocephalae may enhance immunity and improve heart function in aged rats. PMID- 22777212 TI - Advice for travelers. PMID- 22777211 TI - Improvement of atherosclerotic markers in non-diabetic patients after bariatric surgery. AB - BACKGROUND: The objective of this study was to assess the impact of bariatric surgery performed in extremely obese non-diabetic subjects on the following parameters: endothelial function, inflammatory processes (assessed by high sensitivity C-reactive protein [hs-CRP]), carotid artery intima-media thickness (CIMT), and glucose and lipid profiles. METHODS: Forty-seven obese individuals with body mass index >40 kg/m(2) underwent bariatric surgery and returned for post-procedure assessment between 6 and 19 months after surgery. Ninety-three percent of patients were female. Their age ranged from 18 to 65 (mean 41) years old at baseline. Baseline was defined as the maximum of 30 days before surgery. Before and after surgery, all patients were subjected to a brachial artery ultrasound examination to evaluate endothelial-dependent dilation, CIMT by ultrasound, and laboratory analyses including glucose, lipid and inflammatory profiles were performed. RESULTS: Subjects lost an average of 33 % of their original weight (p < 0.001). Flow-mediated dilation showed significant improvement after surgery from 7.4 % to 18.9 % (p < 0.001) on average. There was regression of CIMT, with the median being reduced from 0.8 to 0.5 mm (p < 0.001). The median Hs-CRP reduced from 0.83 to 0.18 mg/dl (p < 0.001), while glucose and lipid profiles were also improved after surgery. CONCLUSIONS: This study shows that severely obese, non-diabetic patients who had pronounced weight loss after bariatric surgery had an overall improvement in brachial flow-mediated dilation, CIMT, high-sensitivity CRP, and glucose and lipid metabolism. The best responses of the brachial flow-mediated dilation after surgery were observed in non-smokers and in younger subjects. PMID- 22777213 TI - 1,12-diazaperylene and 2,11-dialkylated-1,12-diazaperylene iridium(III) complexes [Ir(C^N)2(N^N)]PF6: new supramolecular assemblies. AB - A series of new monocationic iridium(III) complexes [Ir(C^N)(2)(N^N)]PF(6) with "large-surface"alpha,alpha'-diimin ligands N^N (dap = 1,12-diazaperylene, dmedap = 2,11-dimethyl-1,12-diazaperylene, dipdap = 2,11-diisopropyl-1,12-diazaperylene) and different cyclometalating ligands C^N (piq = 1-phenylisoquinoline, bzq = benzo[h]quinoline, ppz = 1-phenylpyrazole, thpy = 2-(2-thienyl)pyridine, ppy = 2 phenylpyridine, meppy = 2-(4-methylphenyl)pyridine, dfppy = 2-(2,4 difluorophenyl)pyridine) were synthesized. The solid structures of the complexes [Ir(piq)(2)(dap)]PF(6), [Ir(bzq)(2)(dap)]PF(6), [Ir(ppy)(2)(dipdap)]PF(6), [Ir(piq)(2)(dmedap)]PF(6), [Ir(ppy)(2)(dap)]PF(6) and [Ir(ppz)(2)(dap)]PF(6) are reported. In [Ir(piq)(2)(dap)]PF(6), the dap ligand and one of the piq ligands of each cationic complex are involved in pi-pi stacking interactions forming supramolecular channels running along the crystallographic c axis. In the crystalline [Ir(bzq)(2)(dap)]PF(6)pi-pi stacking interactions between the metal complexes lead to the formation of a 2D layer structure. In addition, CH-pi interactions were found in all compounds, which are what stabilizes the solid structure. In particular, a significant number of them were found in [Ir(piq)(2)(dap)]PF(6) and [Ir(bzq)(2)(dap)]PF(6). The crystal structures of [Ir(ppy)(2)(dipdap)]PF(6) and [Ir(ppy)(2)(dmedap)]PF(6) are also presented, being the first examples of bis-cyclometalated iridium(iii) complexes with phenanthroline-type alpha,alpha'-diimin ligands bearing bulky alkyl groups in the neighbourhood of the N-donor atoms. These ligands implicate a distorted octahedral coordination geometry that in turn destabilized the Ir-N(N^N) bonds. The new iridium(iii) complexes are not luminescent. All compounds show an electrochemically irreversible anodic peak between 1.15 and 1.58 V, which is influenced by the different cyclometalated ligands. All of the new complexes show two reversible successive one-electron "large-surface" ligand-centred reductions around -0.70 V and -1.30 V. Electrospray ionisation mass spectrometry (ESI-MS) and collision induced decomposition (CID) measurements were used to investigate the stability of the new complexes. Thereby, the stability agreed well with the order of the Ir-N(N^N) bond lengths. PMID- 22777214 TI - Effect of a benzothiadiazole on inducing resistance of soybean to Phytophthora sojae. AB - Effects of benzothidiazole (BTH), an inducer of resistance, were examined in a compatible interaction of soybean seedlings and Phytophthora sojae using electron microscopy and quantitative real-time polymerase chain reaction (qRT-PCR) techniques. Seedlings were sprayed with BTH 2 days before inoculation of hypocotyls with zoospore suspension of P. sojae. In hypocotyls treated with BTH, the infection process of P. sojae was significantly delayed, and also the structures of hyphae and haustorium-like bodies were remarkably altered. These changes included increased vacuolation, plasmolysis, degeneration of cytoplasm, and collapse of hyphae and haustorium-like bodies. Large morphological differences were detected in P. sojae-infected hypocotyl tissue treated with BTH compared with infected but non-treated control tissue. Very thick layers of wall appositions were formed in the host cells contacting with hyphae, whereas such structures were never observed in only P. sojae-infected control hypocotyls. In addition, five pathogenesis-related (PR)-genes were selected to detect their transcription changes using qRT-PCR. Expression of PR-1, PR-3a, PR-3b, PR-9, and PR-10 genes were induced in BTH-treated and P. sojae-inoculated tissue at different times and levels. The up-regulated expression of these genes as well as the morphological defense structures may contribute to disease resistance in soybean hypocotyls to P. sojae. PMID- 22777215 TI - Nasal obstruction following septorhinoplasty: how well does acoustic rhinometry work? AB - Septorhinoplasty aims to improve not only the esthetic appearance but also breathing function of the nose. Although the esthetic improvement can be judged by the patient and the surgeon easily, evaluation of nasal breathing is more complicated. Besides the subjective symptom scores given by the patient, some objective methods have been developed. One of the most widely used of these objective methods is acoustic rhinometry, which gives valuable information about the cross-sectional areas and volumes of the nasal airway as a function of distance from the nostril. Since the introduction of acoustic rhinometry, many papers were reported regarding its efficiency with some conflicting conclusions. Septorhinoplasty has the potential to narrow the nasal airway, especially if it includes lateral osteotomies and hump reduction. We aimed to evaluate the role of rhinoplasty on nasal obstruction with the help of subjective symptom scores and acoustic rhinometry. The study consisted of 26 patients who underwent septorhinoplasty. Before and after surgery, the symptom scores and findings of acoustic rhinometry were collected both before and after decongestion of the nasal mucosa. Symptom scores decreased on both sides, which were statistically significant (p < 0.05), however, the changes in cross-sectional areas of the nasal airway were not statistically significant (p > 0.05). The correlation between the symptom scores and acoustic rhinometry findings was not significant for all levels. The effect of septorhinoplasty on nasal airway and some important maneuvers to protect against nasal obstruction are discussed. PMID- 22777216 TI - JDD: Celebrating 10 years of publishing excellence. PMID- 22777218 TI - Message from the guest editor. PMID- 22777219 TI - Colloidal oatmeal formulations as adjunct treatments in atopic dermatitis. AB - Colloidal oatmeal has been used for decades to soothe and ameliorate atopic dermatitis and other pruritic and/or xerotic dermatoses. In-vitro and/or in-vivo studies have confirmed the anti-inflammatory, barrier repair, and moisturizing properties of this compound. A broad set of studies has been conducted in recent years to assess the effects of colloidal oatmeal as adjunct treatment in the management of atopic dermatitis (AD). This paper will review these studies. In these investigations, patients in all age groups (3 months to 60 years) with mild to moderate atopic dermatitis were included and allowed to continue their prescribed topical medications. These studies found that the daily use of moisturizers and/or cleansers containing colloidal oatmeal significantly improved many clinical outcomes of atopic dermatitis from baseline: investigator's assessment (IGA), eczema area and severity index (EASI), itch, dryness, and quality of life indices. Safety results showed that the formulations were well tolerated in babies, children, and adults with AD. PMID- 22777220 TI - Propranolol as the first-line therapy for infantile hemangiomas: preliminary results of two centers. AB - AIM: Despite a mostly self-limiting course, infantile hemangiomas can cause severe functional and/or cosmetic problems. The aim of this study was to determine the efficiency of propranolol treatment on infantile hemangiomas. METHODS: Sixty-seven infantile hemangioma patients were included in propranolol protocol in two institutions from 2009 to 2011. Participants included 36 boys and 31 girls. An associate protocol with radiology and pediatric cardiology was constructed for appropriate patient selection. Patients received a dose of 2 mg/kg/day, and all were admitted for the first 24 hours of therapy. RESULTS: Sixty-seven patients were included in the study. Mean age at the initiation of therapy was 7 months (1 to 24 months), and eleven patients were older than 12 months of age when propranolol was started. All patients showed improvement with varying responses. No side effects were detected during the treatment. CONCLUSION: Previously defined treatments for hemangiomas were efficient, yet had a limited usage because of side effects. Propranolol, with a high efficacy (not as total involution but stabilization and regression) and feasibility deserves to be the first line therapy for infantile hemangiomas even after the proliferation phase. PMID- 22777221 TI - Multiples in dermatology: markers for special considerations in diagnosis, therapy, and prognosis. AB - Multiples of certain cutaneous lesions should alert the clinician to a wider differential diagnosis and possible systemic associations although the individual skin lesion is often benign in nature and banal in appearance. This article focuses on such findings in selected multiple cutaneous lesions that may be classified according to the primary cutaneous feature as vascular, pigmentary, nevoid hamartomas, and tumors/neoplastic conditions. The clinical presentation of each entity and its significance, appropriate diagnostic evaluation, therapeutic and prognostic considerations and pertinent differential diagnoses will be reviewed. PMID- 22777222 TI - Moderate to severe acne in adolescents with skin of color: benefits of a fixed combination clindamycin phosphate 1.2% and benzoyl peroxide 2.5% aqueous gel. AB - OBJECTIVE: Acne is common in adolescents and especially difficult to manage in people with color. A fixed combination of clindamycin phosphate and benzoyl peroxide (BPO) (clindamycin phosphate 1.2%/BPO 2.5% gel) was evaluated to determine its utility in treating moderate to severe acne in adolescents with skin of color. METHODS: Three hundred thirty-seven adolescent acne subjects (aged 12 to <18 years) with skin of color were evaluated from 2 multicenter, double blind studies. Subjects were randomized to receive clindamycin phosphate 1.2%/BPO 2.5% gel or vehicle, once daily for 12 weeks. Efficacy and tolerability were evaluated. Data were compared with an adolescent (A) and skin of color (B) cohort from the same pivotal study enrolling 2,813 subjects. RESULTS: Superior mean percent reductions in inflammatory, noninflammatory, and total lesion counts were observed in subjects receiving clindamycin phosphate 1.2%/BPO 2.5% gel compared to vehicle. At week 12, clindamycin phosphate 1.2%/BPO 2.5% gel showed similar lesion reduction compared to groups A and B (P<0.001). Treatment success with clindamycin phosphate 1.2%/BPO 2.5% gel, assessed by investigator and subject, was superior to vehicle and comparable to that seen in groups A and B (P<0.001). Clindamycin phosphate 1.2%/ BPO 2.5% gel was associated with a low incidence of treatment-related AEs and a favorable cutaneous tolerability profile. CONCLUSIONS: Clindamycin phosphate 1.2%/BPO 2.5% gel has been shown to be effective, safe, and well tolerated in moderate to severe acne in adolescents with skin of color. PMID- 22777223 TI - A review of beta antagonist treatment for infantile hemangioma. AB - Infantile hemangiomas are benign vascular neoplasms of childhood that often have implications on development, cosmesis, and comfort. Traditional therapy has involved either observation or corticosteroids, depending on location and size. Recent studies have reported the successful use of beta-adrenergic antagonists in treating infantile hemangiomas. This succinct review discusses the properties and current applications of beta-adrenergic antagonists as well as the established treatments for infantile hemangioma. PMID- 22777224 TI - The effect of benzoyl peroxide 9.8% emollient foam on reduction of Propionibacterium acnes on the back using a short contact therapy approach. AB - Benzoyl peroxide (BP) exerts its therapeutic effect for acne vulgaris through reduction of Propionibacterium acnes. A 1.0 to 2.0 log reduction in P acnes has been demonstrated primarily on the face with use of "leave-on" BP formulations, but also with some BP cleansers. In addition to use for facial acne vulgaris, cleanser formulations of BP are commonly used for truncal acne vulgaris due to ease of use on a large body-surface area and to avoid bleaching of fabric. To date, evaluation of P acnes reduction on the trunk has not been well studied with BP formulations, especially with the use of recognized and standardized methods to accurately determine P acnes colony counts. A previous study demonstrated that a BP 8% cleanser did not reduce counts of P acnes on the back when subjects were instructed to apply the cleanser in the shower, allow it to dry for 20 seconds on the skin, and then rinse off the cleanser. Evaluation of specified time intervals between application on the back and rinsing with BP formulations would help to better define the necessary skin contact time associated with high reductions of P acnes (>90%), recognizing also the potential roles of BP concentration and vehicle. This 2 week study using quantitative bacteriologic cultures evaluates the effectiveness of BP 9.8% emollient foam in reducing P acnes levels on the back with 2 minutes of skin contact time and compares results with a BP 5.3% "leave-on" emollient foam formulation. Short contact therapy utilizing a 2 minute skin contact time with BP 9.8% emollient foam used once daily over a 2 week duration was highly effective in reducing the quantity of P acnes organisms on the back and provided comparable colony count reduction to "leave on" therapy using BP 5.3% emollient foam. PMID- 22777226 TI - Optimal management of papulopustular rosacea: rationale for combination therapy. AB - The pathophysiology of papulopustular rosacea (PPR) is primarily characterized by inflammation associated with several factors such as abnormal innate immune response, neurovascular dysregulation, stratum corneum barrier dysfunction, and depletion of antioxidant reserve, with no definitive evidence supporting an underlying microbial etiology. Several molecular inflammatory pathways have now been identified that enable the development of therapeutic agents that target the signs and symptoms of disease by modifying specific pathophysiological mechanisms. Available evidence demonstrates that topical and oral agents commonly used to treat PPR appear to modify some of these pathophysiological mechanisms and may prove to be complimentary when used in combination potentially leading to better therapeutic outcomes. During the past two decades, six clinical studies have been published on the benefits of combining oral and topical therapies for PPR. Four studies suggest that doxycycline, including anti-inflammatory dose doxycycline (doxycycline 40 mg modified-release capsule once daily) can be combined with topical metronidazole or azelaic acid in patients with PPR to achieve more rapid control of a flare. At present, subantimicrobial dosing of a tetracycline agent that also maintains anti-inflammatory activity has only been established with doxycycline. Although antibiotic doses of tetracycline agents (such as doxycycline, minocycline, and tetracycline) are known to be effective for PPR, the use of subantimicrobial dosing of doxycycline avoids the risk of antibiotic resistance. PMID- 22777225 TI - Modulation of cytokine and nitric oxide production by keratinocytes, epithelial cells, and mononuclear phagocytes in a co-culture model of inflammatory acne. AB - INTRODUCTION: Ultraviolet B (UVB, 290 nm to 320 nm) has been reported to modulate the cytokine-mediated inflammatory process in various inflammatory skin conditions, including production of TNF-alpha, IL-1alpha, IL-6, IL-8, and IL-10. We constructed an in vitro model system involving co-culture of different cell types to study the effect of UVB on the inflammatory process using nitric oxide (NO) and tumor necrosis factor (TNF)-alpha as markers of inflammation. OBJECTIVE: This study was conducted to quantitatively assess the products secreted by human epithelial keratinocytes in the presence and absence of macrophages/monocytes. METHODS: Cells were exposed to UVB radiation (50 mJ to 200 mJ per cm2) or treated with bacterial lipopolysaccharide (LPS) as stimulator of inflammatory response. Nitric oxide (NO) was measured by modified Griess assay and TNF-alpha was measured by quantitative ELISA. For the co-culture system, SC monocytes were seeded in a 24-well Transwell tissue culture plate whereas irradiated keratinocytes were seeded in the individual baskets subsequently placed on top of the monocyte cultures, and samples of culture supernatants were collected at 1 to 6 days. RESULTS: When primary human epidermal keratinocytes (NHEK) were irradiated with UVB, a dose-dependent stimulation of TNF-alpha production was observed (33% to 200% increase). TNF-alpha production was not changed significantly in SC monocytes/NHEK co-culture. In contrast, when macrophages were irradiated with UVB, significant inhibition of NO production (40% suppression, P<0.001) was seen. CONCLUSION: This improved model of cutaneous inflammation could use multiple cells to study their interactions and to offer convenience, reproducibility, and a closer approximation of in vivo conditions. PMID- 22777227 TI - Nanotechnology and the diagnosis of dermatological infectious disease. AB - Despite advances in diagnostics and therapeutics, infectious diseases continue to be a major cause of morbidity and mortality, surpassing cardiovascular diseases and cancer. Accurate identification of causative pathogens is critical to prevent the spread of infectious diseases and to deliver appropriate and timely therapy. Various limitations ranging from cost to lengthy yield times of current diagnostic modalities highlight the need for new approaches. Nanotechnology represents an innovative direction offering many advantages for pathogen detection and identification. Through surface modifications, nanoparticles can be tailored to bind microbial surface markers, nucleic acids, and toxins. Combining these nanoparticles with both standard and developing detection technologies has led to the development of faster, more sensitive, and more economical diagnostic assays. This review will focus on the diagnostic advances that utilize fluorescent, metallic, and magnetic nanomaterials, highlighting their potential applications in the diagnosis of infectious dermatological conditions. PMID- 22777228 TI - Treatment outcomes for tinea capitis in a skin of color population. AB - BACKGROUND: Tinea capitis periodically undergoes demographic shifts in causative dermatophyte and therapeutic response to oral anti-fungal therapy. OBJECTIVE: To determine prevalent fungal species and response to standard antifungal therapy in inner-city children of color. METHODS: An IRB-approved chart review of demographic, clinical, diagnostic, and therapeutic data was conducted for children and young adults (0 to 18 years of age) who had scalp fungal culture performed for scalp hyperkeratosis and/or alopecia over a 2.5 year time-period. Supplemental parental phone interview was performed for missing data points. RESULTS: A total of 84 patients with final diagnosis of tinea capitis were identified-52% male, 60.6% African-American, 28.2% Hispanic, and 9.9% Caucasian. Complete resolution at 4 weeks was uncommon in all demographic groups (Hispanic: 11.7%, African-American: 41.3%). The Hispanic group and the youngest patients (aged less than 4 years) were less likely to respond to initial therapy, but the results were not significant. Of the 80 tinea capitis patients initially treated with griseofulvin, 41 out of 54 children (76%) had complete response to micronized suspension +/- crushed tablet (33% required shift to tablets from suspension) and 20 out of 26 (76.9%) cleared on crushed tablets alone. Of the 19 griseofulvin failures, 5 cleared on fluconazole suspension, 7 on terbinafine sprinkles, 3 on itraconazole therapy, and 4 were lost to follow-up. Of the 47 patients who could be evaluated long-term after a single course of oral griseofulvin at 6 weeks or greater, 38 had documented long-term mycological cure (80.8%) and 42 had long-term clinical cure (89%). Trichophyton tonsurans (n=40) was the most prevalent causative species identified on culture, followed by Alternaria species (n=10) and Microsporum canis (n=1). LIMITATIONS: Retrospective chart review: patient population has a high rate of usage of over-the-counter antifungal creams and shampoos, affecting culture results. CONCLUSIONS: Tinea capitis is still the most common cause of Trichophyton tonsurans in New York City. Response rates to griseofulvin are similar to rates seen in the 1970s, but require higher dosing and conversion to crushed tablets in partial responders. Usage of crushed ultramicronized griseofulvin, terbinafine sprinkles, itraconazole, and fluconazole are alternative regimens for those children whose tinea capitis does not clear on griseofulvin suspension. PMID- 22777229 TI - Efficacy and tolerability of retapamulin 1% ointment for the treatment of infected atopic dermatitis: a pilot study. AB - BACKGROUND: Patients with atopic dermatitis (AD) are known to have a predisposition to colonization or infection by microbial organisms, including both Staphylococcus aureus and herpes simplex virus (HSV). S aureus infection leads to exacerbation of eczema and may induce flares in atopic skin by mediating inflammation. Retapamulin 1% ointment is a unique topical antibiotic formulation that may be a suitable option for the treatment of clinically infected AD. STUDY DESIGN: A single-center, open-label pilot study was conducted to investigate the efficacy and safety of retapamulin 1% (Altabax, Stiefel/ GlaxoSmithKline) ointment for the treatment of secondarily infected atopic dermatitis in subjects aged 9 months to 98 years old (n=29). RESULTS: Twice-daily application of retapamulin 1% produced a mean 8.1-point reduction from baseline in the mean Skin Infection Rating Scale score. The majority of subjects achieved clinical cure with topical retapamulin therapy. Retapamulin 1% ointment was effective against S aureus isolates, including methicillin-resistant Staphylococcus aureus (MRSA). Treatment was well tolerated. CONCLUSION: Retapamulin 1% is effective for the treatment of atopic dermatitis infected with S aureus, and demonstrates efficacy against both methicillin-susceptible and methicillin-resistant strains. Given its efficacy and good tolerability in this pilot study, retapamulin 1% ointment should be further evaluated as a treatment for infected atopic dermatitis. It may provide convenience and efficacy with a low risk for development of bacterial resistance. PMID- 22777230 TI - Combined antibiotic/corticosteroid cream in the empirical treatment of moderate to severe eczema: friend or foe? AB - BACKGROUND: Eczema is a common atopic disease associated with pruritus, sleep disturbance, and impaired quality of life. Staphylococcus aureus colonization/infection is important in its pathophysiology. AIM: To evaluate the prevalence of S aureus colonization/infection and the efficacy and acceptability of a combined antibiotic/corticosteroid cream in the empirical treatment of eczema. METHODS: Consecutive patients with moderate to severe eczema were recruited. Swab and cultures from the right antecubital fossa and the worst eczematous area, disease severity (SCORAD) and quality of life (Children's Dermatology Life Quality Index, CDLQI), skin hydration (SH), and transepidermal water loss (TEWL) were obtained prior to and following a two week twice-daily course of treatment with a fucidin/corticosteroid cream. General acceptability of treatment (GAT) was documented at completion. RESULTS: Thirty-five patients (63% males; mean age 13.5, standard deviation 3.6 years; with 21 moderate and 14 severe disease) were recruited. At start, S aureus was isolated from the right antecubital fossa and the worst affected areas in 66% and 71% of these patients, respectively. At completion, S aureus was isolated in 23% and 40% at the antecubital fossae and worst affected areas (P=0.001 and P=0.003, respectively). No methicillin-resistant S aureus was isolated in this series, but the percentage of fucidin-resistant S aureus increased from 8% to 58% (P<0.001). Disease severity and quality of life were significantly improved (pre-Objective SCORAD and post-Objective SCORAD were 38.4+/-13.7 and 29.7+/-14.2, P<0.001; pre-CDLQI and post-CDLQI were 9.4+/-5.2 and 7.1+/-4.8, P<0.001). At the right antecubital fossa, skin hydration improved from 30.8+/-14.2 to 36.7+/-15.2 (P=0.015); and TEWL from 10.7+/-2.3 to 9.4+/-2.2 (P<0.001). Eighty percent of patients found the treatment good or very good, and only one (3%) patient found it unacceptable. CONCLUSIONS: The most prevalent organism in moderate to severe eczema was S aureus. Usage of the combined fucidin/corticosteroid cream is convenient and associated with a reduction in disease severity, improvement in quality of life, SH, and TEWL, but caution has to be taken with emergence of fucidin-resistant S aureus. PMID- 22777231 TI - Reconstruction of full-thickness defects with bovine-derived collagen/elastin matrix: a series of challenging cases and the first reported post-burn facial reconstruction. AB - Reconstruction of full-thickness defects may benefit from integration of dermal substitutes, which serve as a foundation for split-thickness skin grafts, thus enhancing short and long-term results. We present a series of 7 patients who were treated between 2010 and 2012 for complicated full-thickness defects by the second-generation collagen/elastin matrix Matriderm(r) covered by a split thickness skin graft. The defects resulted from malignancy resection, trauma, and post-burn scar reconstruction. Overall graft take was excellent and no complications were noted regarding the dermal substitute. Graft quality was close to normal skin in terms of elasticity, pliability, texture, and color. Good contour and cushioning of defects in weight bearing areas was also achieved. Matriderm was found to be a useful adjunct to full-thickness defect reconstruction, especially in difficult areas where the desired result is a scar of the highest quality possible. PMID- 22777233 TI - Effective topical combination therapy for treatment of lichen striatus in children: a case series and review. AB - Lichen striatus (LS) is an uncommon linear dermatosis that is primarily seen in children from 4 months to 15 years of age. While some of these eruptions are asymptomatic, others can be quite pruritic. In darker-skinned individuals, post inflammatory hypopigmentation can be significant and may provide a cause for concern for the patients and/or their parents. In our case series of 4 patients, we observed rapid resolution of LS by combining a topical retinoid with a topical steroid. To our knowledge, this is the first report of successful treatment with this kind of combination therapy in the English literature. The patients not only achieved satisfying cosmesis, but also complete resolution of their pruritus. The most common side effect of topical tazarotene is localized irritation at treatment sites, but the patients in this particular series tolerated the treatment well. PMID- 22777235 TI - Periorbital syringoma treated with radiofrequency and carbon dioxide (CO2) laser in 5 patients. AB - Syringomas are common benign eccrine ductal adnexial tumors, commonly found in periorbital area. Periorbital syringomas are aesthetically disturbing difficult to treat. Many treatment modalities are described in the literature, including topical and surgical methods, with potential problems such as postinflammatory hyper- and hypopigmentation, low efficacy, or scar formation. We present 5 patients with syringoma treated with the combination of radiofrequency ablation and carbon dioxide (CO2) lasers. Using low-energy parameters on the CO2 laser, and low energy on the radiofrequency, we could complement both treatments maximizing the destruction of the tumors and minimizing the adverse effects in only two sessions. This is a relatively easy, safe, and less painful treatment, with good cosmetic results on periorbital syringomas. PMID- 22777236 TI - A case of perforating dermatosis in a patient with primary sclerosing cholangitis. PMID- 22777237 TI - The outer aspect of our inner anxiety: the skinny on stress. PMID- 22777240 TI - HOXA1 gene is not potentially related to ventricular septal defect in Chinese children. AB - The HOXA1 gene plays a fundamental role in embryonic morphogenesis. Recent studies in humans and mice have indicated that HOXA1 plays a previously unrecognized role in cardiovascular system development. Congenital heart disease (CHD), particularly ventricular septal defect (VSD), might be a clinically isolated manifestation of HOXA1 mutations. The purpose of the present study was to identify potential pathological mutations in the HOXA1 gene in Chinese children with VSD and to gain insight into the etiology of CHD. A total of 340 nonsyndromic VSD patients and 200 normal subjects were sampled. Two exons and the nearby introns of the human HOXA1 gene were amplified using polymerase chain reaction (PCR). The PCR products were purified and directly sequenced. However, no nonsynonymous mutations in the coding regions of the HOXA1 gene were observed: Only two novel synonymous mutations (c.C210T p.His70His, and c.T861A p.Arg287Arg) were found in two patients. Two previously reported single and multiple histidine deletion variants were identified in both normal and VSD patients. To our knowledge, this is the first study to investigate the role of the HOXA1 gene in CHD. Although our results did not show any pathogenic HOXA1 mutation, our results suggest that VSD might not be a clinically isolated manifestation of HOXA1 mutations. PMID- 22777241 TI - Characterization of a cold-adapted glutathione synthetase from the psychrophile Pseudoalteromonas haloplanktis. AB - Glutathione (GSH) biosynthesis occurs through two ATP-dependent reactions, usually involving distinct enzymes; in the second step of this process, catalysed by glutathione synthetase (GshB), GSH is formed from gamma-glutamylcysteine and glycine. A recombinant form of GshB from the cold-adapted source Pseudoalteromonas haloplanktis (rPhGshB) was purified and characterised. The enzyme formed a disulfide adduct with beta-mercaptoethanol, when purified in the presence of this reducing agent. The homotetrameric form of rPhGshB observed at high protein concentration disassembled into two homodimers at low concentration. A new method for directly determining the rPhGshB activity was developed, based on [gamma-(32)P]ATP hydrolysis coupled to the GSH synthesis. The ATPase activity required the presence of both gamma-glutamylcysteine and glycine and its optimum was reached in the 7.4-8.6 pH range; a divalent cation was absolutely required for the activity, whereas monovalent cations were dispensable. rPhGshB was active at low temperatures and had a similar affinity for ATP (K(m) 0.26 mM) and gamma glutamylcysteine (K(m) 0.25 mM); a lower affinity was measured for glycine (K(m) 0.75 mM). The oxidised form of glutathione (GSSG) acted as an irreversible inhibitor of rPhGshB (K(i) 10.7 mM) and formed disulfide adducts with the enzyme. rPhGshB displayed a great temperature-dependent increase in its activity with an unusually high value of energy of activation (75 kJ mol(-1)) for a psychrophilic enzyme. The enzyme was moderately thermostable, its half inactivation temperature being 50.5 degrees C after 10 min exposure. The energy of activation of the heat inactivation process was 208 kJ mol(-1). To our knowledge, this is the first contribution to the characterization of a GshB from cold-adapted sources. PMID- 22777242 TI - Expansion of Mesenchymal Stem/Stromal cells under xenogenic-free culture conditions. AB - Mesenchymal Stem/Stromal cells (MSCs) are increasingly applied in cell-based regenerative medicine. To yield clinically relevant cell doses, ex vivo expansion of MSCs is required to be compliant with good manufacturing practice (GMP) guidelines. A lack of standardization and harmonization seems to hamper rapid progress in the translational phase. Most protocols still use fetal bovine serum (FBS) to expand MSCs. However, the high lot-to-lot variability, risk of contamination and immunization call for xenogenic-free culture conditions. Chemically defined media are the ultimate achievement in terms of standardization. These media, however, need to maintain all key cellular and therapy-relevant features of MSCs. Because of the numerous constituents of FBS, the development of such chemically defined media with an optimal composition of the few essential factors is only beginning. Meanwhile, various human blood derived components are under investigation, including human plasma, human serum, human umbilical cord blood serum and human platelet derivatives such as platelet lysate. PMID- 22777243 TI - Alzheimer disease: Amyloid-beta immunotherapy CAD106 passes first safety test in patients with Alzheimer disease. PMID- 22777245 TI - Epilepsy: maximizing cognitive outcomes in epilepsy. PMID- 22777248 TI - Correspondence: Measuring dystrophin-faster is not necessarily better. PMID- 22777249 TI - Motor neuron disease: common conformational change identified in toxic SOD1 mutants-a novel diagnostic marker for ALS? PMID- 22777252 TI - Imaging secondary metabolism of Streptomyces sp. Mg1 during cellular lysis and colony degradation of competing Bacillus subtilis. AB - Soil streptomycetes are saprotrophic bacteria that secrete numerous secondary metabolites and enzymes for extracellular functions. Many streptomycetes produce antibiotics thought to protect vegetative mycelia from competing organisms. Here we report that an organism isolated from soil, Streptomyces sp. Mg1, actively degrades colonies and causes cellular lysis of Bacillus subtilis when the organisms are cultured together. We predicted that the inhibition and degradation of B. subtilis colonies in this competition depends upon a combination of secreted factors, including small molecule metabolites and enzymes. To begin to unravel this complex competitive phenomenon, we use a MALDI imaging mass spectrometry strategy to map the positions of metabolites secreted by both organisms. In this report, we show that Streptomyces sp. Mg1 produces the macrolide antibiotic chalcomycin A, which contributes to inhibition of B. subtilis growth in combination with other, as yet unidentified factors. We suggest that efforts to understand competitive and cooperative interactions between bacterial species benefit from assays that pair living organisms and probe the complexity of metabolic exchanges between them. PMID- 22777251 TI - Late-stage Parkinson disease. AB - The cardinal symptoms of Parkinson disease (PD) are asymmetrical bradykinesia, rigidity, resting tremor and postural instability. However, the presence and spectrum of, and disability caused by, nonmotor symptoms (NMS) are being increasingly recognized. NMS include dementia, psychosis, depression and apathy, and are a major source of disability in later stages of PD, in association with axial symptoms that are resistant to levodopa therapy. The model of clinical progression of PD should, therefore, incorporate NMS, instead of being restricted to motor signs and levodopa-induced motor complications. Patients with disabling motor complications are classified as having advanced PD, which has been thought to represent the ultimate stage of disease. However, deep brain stimulation to treat motor complications has dramatically changed this scenario, with implications for the definition of advanced-stage disease. As treatment improves and survival times increase, patients are increasingly progressing to a later phase of disease in which they are highly dependent on caregivers, and disability is dominated by motor symptoms and NMS that are resistant to levodopa. In this article, we review the changing landscape of the later stages of PD, and propose a definition of late-stage PD to designate patients who have progressed beyond the advanced stage. PMID- 22777253 TI - Overproduction and biological activity of prodigiosin-like pigments from recombinant fusant of endophytic marine Streptomyces species. AB - Thirty-four endophytic marine Actinomycetes isolates were recovered from the Egyptian marine sponge Latrunculia corticata, out of them 5 isolates (14.7 %) showed red single colonies on yeast-CzAPEK plates. Isolates under the isolation code NRC50 and NRC51 were observed with the strongest red biomass. After application of protoplast fusion between NRC50 and NRC51 isolates, 26 fusants were selected and produced widely different amounts of prodigiosin-like pigments (PLPs) on different fermentation media. Among them fusant NRCF69 produced 79 and 160.4 % PLPs more than parental strains NRC50 and NRC51, respectively. According to the analysis of 16S rDNA sequence (amplified, sequenced, and submitted to GenBank under Accession no. JN232405 and JN232406, respectively), together with their morphological and biochemical characteristics, parental strains NRC50 (P1) and NRC51 (P2) were identified as Streptomyces sp. and designated as Streptomyces sp. NRC50 and Streptomyces sp. NRC51. This study describes a low cost, effective production media by using peanut seed broth, sunflower oil broth or dairy processing wastewater broth alone, or supplemented with 0.5 % mannitol that supports the production of PLPs by the Streptomyces fusant NRCF69 under study (42.03, 40.11, 36.7 and 47 g L(-1), respectively). PLPs compounds exhibited significant cytotoxic activities against three human cancer cell lines: colon cancer cell line (HCT-116), liver cancer cell line (HEPG-2) and breast cancer cell line (MCF-7) and antimycotic activity against clinical dermatophyte isolates of Trichophyton, Microsporum and Epidermophyton. PMID- 22777255 TI - [Rivaroxaban in the prevention and treatment of thromboembolic disorders]. AB - Rivaroxaban (Xarelto((r))) is a new anticoagulant for the prevention and treatment of thromboembolic disorders. Rivaroxaban inhibits coagulation factor Xa directly, has high oral bioavailability, shows low propensity for drug-drug interactions and requires no routine coagulation monitoring. In patients undergoing elective knee or hip replacement surgery rivaroxaban (10 mg/d) is highly effective to prevent venous thromboembolism. In patients with non-valvular atrial fibrillation rivaroxaban (20 mg/d) has been approved to prevent stroke or systemic embolism. The favourable benefit-risk profile of rivaroxaban in the treatment of deep vein thrombosis (DVT) was shown in EINSTEIN-DVT and led to its clinical approval (twice daily 15 mg for 3 weeks, followed by 20 mg/d). Based on ATLAS-ACS-TIMI-51 which has shown that rivaroxaban (2.5 mg twice daily) reduced thrombotic cardiovascular events and mortality in patients with a recent acute coronary syndrome, the approval of low dose rivaroxaban has been submitted for this indication. Taken together, rivaroxaban may become an effective alternative to standard anticoagulants in the prevention and treatment of thromboembolic disorders. PMID- 22777258 TI - Cutting-edge questions about CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids). PMID- 22777261 TI - Ataxia and weakness in a young woman. PMID- 22777259 TI - Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients. AB - BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE: To describe the disease course of CLIPPERS. DESIGN: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING: Academic research. PATIENTS: Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES: The therapeutic management of CLIPPERS was evaluated. RESULTS: Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, >=5) and brainstem and spinal cord atrophy. CONCLUSIONS: CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses. PMID- 22777264 TI - Lack of response to pulse cyclophosphamide in neuromyelitis optica: evaluation of 7 patients. PMID- 22777265 TI - IDEAL for CCSVI research. PMID- 22777267 TI - Physical activity and AD-related pathology. PMID- 22777269 TI - [New oral anticoagulants. Significance for dermatology and phlebology]. AB - Venous thromboembolism and atrial fibrillation are common and are treated with vitamin K antagonists in 1.7% of the total population in the western world. The limitations of the vitamin K antagonists and of heparin have led to the development of new oral drugs. These drugs inhibit thrombin or factor Xa and can be given in a fixed dosage; they have a broad therapeutic margin and relatively few drug interactions. Specific risks and problems also are associated with the new drugs such as interference with common coagulation tests without being able to draw any conclusion as to the actual bleeding risk and the lack of specific antidotes. No established coagulation monitoring is available. The article gives reviews the current knowledge and provides practical advice on how to use the new drugs for the approved indications such as knee and hip replacement, therapy of deep venous thrombosis and of atrial fibrillation. Beyond that, recommendations are given for perioperative management and for change of treatment. PMID- 22777270 TI - Multiple fungal brain abscesses in a child with acute lymphoblastic leukemia. AB - Fungal infection is a severe problem in children suffering from cancer. We report a case of a four-year-old girl who was diagnosed with acute lymphoblastic leukemia and multiple Aspergillus niger abscesses at the induction phase of the treatment. She was treated with granulocyte transfusions, liposomal amphotericin B with a combination of voriconazole for four months, followed by oral variconazole alone for 17 months. She was successfully treated with this combination without any sequel, and the planned chemotherapy was also completed. Our experience revealed that antifungal treatment including intravenous amphotericin B and variconazole augmented by granulocyte transfusion is an alternative option for the management of this catastrophic complication. PMID- 22777271 TI - High resolution spatial mapping of brominated pyrrole-2-aminoimidazole alkaloids distributions in the marine sponge Stylissa flabellata via MALDI-mass spectrometry imaging. AB - A number of pharmacologically active brominated pyrrole-2-aminoimidazole (B-P-2 AI) alkaloids have been isolated from several families of marine sponges, including those belonging to the genus Stylissa. In the present study, MALDI mass spectrometry imaging (MALDI-imaging) was applied to determine the spatial distribution of B-P-2-AIs within 20 MUm cross sections of S. flabellata. A number of previously characterised B-P-2-AIs were readily identified by MALDI-imaging and confirmed by MS-MS and NMR profiling. Unknown B-P-2-AIs were also observed. Discrete microchemical environments were revealed for several B-P-2-AIs including dibromophakellin which was localised within the external pinacoderm and internal network of choanoderm chambers. Additionally, dibromopalau'amine and konbu'acidin B were also found to be confined to the choanoderm, while sceptrin was found to be highly abundant within the mesohyl. Further brominated compounds of unknown structure were also observed to have distinct localisation in both choanoderm chambers and the pinacoderm. These findings provide insights into the chemical ecology of S. flabellata, as most B-P-2-AIs were found on highly exposed surfaces, where they may act to prevent pathogens, predation and/or biofouling. Moreover this study demonstrates the power of MALDI-imaging to visualise the location of a range of metabolites in situ and to characterise compounds by MS-MS directly from intact specimens without the need for extraction. These methodologies facilitate selective targeting of micro-regions of sponge to screen for symbiotic microbial candidates or genes that may be involved in the production of the correlated compounds, and may represent a change in paradigm for natural product drug development. PMID- 22777272 TI - Raising doubts about the pathogenicity of mitochondrial DNA mutation m.3308T>C in left ventricular hypertraveculation/noncompaction. PMID- 22777273 TI - Endoscopic total corpus callosotomy: cadaveric demonstration of a new approach. AB - BACKGROUND: Callosotomy is a surgical option for treatment of a small number of patients with intractable seizures who are not candidates for surgical resection. The procedure is done conventionally with the aid of a microscope. In this article, we describe a new technique of endoscopic callosotomy through a parasagittal burr hole in a cadaveric model. METHODS: We utilized this technique with a single frontal burr hole. Callosotomies were performed on 4 silicon injected cadaver heads in our minimally invasive neurosurgical laboratory. RESULTS: We were able to successfully perform total callosotomies in all cadaveric specimens without injury to the adjacent neurovascular structures. The advantages of our technique over microsurgery are the minimally invasive nature of the exposure and the improved visualization of the vascular structures near the rostrum and genu of the corpus callosum. A potential disadvantage we anticipate is the difficulty controlling bleeding in the event of vascular injury. CONCLUSION: We believe that this minimally invasive approach could have potential clinical applications. PMID- 22777274 TI - An overview on mixed action drugs for the treatment of overactive bladder and detrusor overactivity. AB - OBJECTIVES: To provide an overview on the efficacy, tolerability, safety and health-related quality of life (HRQoL) of drugs with a mixed action used in the treatment of overactive bladder (OAB). EVIDENCE ACQUISITION: MEDLINE database and abstract books of the major conferences were searched for relevant publications from 1966 to 2011 and using the key words 'overactive bladder', 'detrusor overactivity', 'oxybutynin', 'propiverine', and 'flavoxate'. Two independent reviewers considered publications for inclusion and extracted relevant data, without performing a meta-analysis. EVIDENCE SYNTHESIS: Old and conflicting data do not support the use of flavoxate, while both propiverine and oxybutynin were found to be more effective than placebo in the treatment of OAB. Propiverine was at least as effective as oxybutynin but with a better tolerability profile even in the pediatric setting. Overall, no serious adverse event for any product was statistically significant compared to placebo. Improvements were seen in HRQoL with treatment by the oxybutynin transdermal delivery system and propiverine extended release. CONCLUSIONS: While there is no evidence to suggest the use of flavoxate in the treatment of OAB, both oxybutynin and propiverine appear efficacious and safe. Propiverine shows a better tolerability profile than oxybutynin. Both drugs improve HRQoL of patients affected by OAB. Profiles of each drug and dosage differ and should be considered in making treatment choices. PMID- 22777275 TI - Drugs for insomnia. PMID- 22777276 TI - Patterns of initial disease recurrence after resection of biliary tract cancer. AB - OBJECTIVES: This study aimed to provide further insights into the indications for adjuvant therapeutic strategies via analysis of the sites of initial recurrence after resection of gallbladder cancer (GBC) and intrahepatic (IHC) and extrahepatic cholangiocarcinoma (EHC). METHODS: Patients with biliary tract cancer who underwent potentially curative resection were identified from the database. Sites of initial disease recurrence were categorized as locoregional or distant. RESULTS: Between March 2001 and April 2009, 231 patients underwent curative resection. Initial GBC and IHC recurrence involving a distant site occurred in 70.8 and 86.8% patients, respectively, compared to 56.9% patients with EHC (p = 0.002). The median time to disease recurrence (TTR) was shorter among the GBC and IHC groups compared with that in EHC patients (6.3 and 6.7 vs. 13.1 months, respectively; p = 0.003). Moreover, median times to distant recurrence in GBC and IHC groups were shorter than that in EHC (5.8 and 6.5 vs. 14.1 months, respectively; p = 0.002). CONCLUSIONS: After resection, recurrent GBC and IHC are more likely to involve a distant site and are associated with significantly shorter TTR than recurrent EHC. These findings suggest that an adjuvant therapeutic strategy targeting distant disease is likely to have a significant impact on the overall management of GBC and IHC. PMID- 22777278 TI - Pathogenicity of the transition m.3308T>C in left ventricular hypertrabeculation/noncompaction. PMID- 22777277 TI - Prevalence of the metabolic syndrome in patients with borderline personality disorder: results from a cross-sectional study. AB - Metabolic syndrome (MetS) is an important risk factor for the development of type 2 diabetes and coronary artery disease. We aimed to compare the MetS prevalence in patients with borderline personality disorder (BPD) with comparison subjects followed in primary care from a similar region. One hundred and thirty-five BPD patients according to DSM-IV diagnostic criteria were compared to 1009 subjects from primary care. We used the American Heart Association/National Heart, Lung and Blood Institute criteria to determine the rate of MetS. The age-standardized prevalence of MetS was more than double in patients with BPD compared to comparison subjects (23.3 vs. 10.6 %, p < 0.05). Regarding individual MetS criteria, hyperglycemia was significantly more prevalent in both genders (p < 0.05). Abdominal obesity (p < 0.05) and hypertriglyceridemia (p < 0.05) were significantly higher only in women with BPD. Within BPD patients, an increased rate of MetS was associated with higher BMI (p = 0.004), age (p = 0.03), treatment with second-generation antipsychotics (quetiapine, olanzapine and clozapine; p = 0.032), dysthymia (p = 0.031), panic disorder (p = 0.032), benzodiazepine dependency (p = 0.015) and binge eating disorder p = 0.02). Our results demonstrate an increased MetS rate, dysregulated glucose and lipid metabolism in patients with BPD. Cardiometabolic monitoring and careful screening for physical health conditions among people with BPD is warranted. PMID- 22777279 TI - Staphylococcal phage 2638A endolysin is lytic for Staphylococcus aureus and harbors an inter-lytic-domain secondary translational start site. AB - Staphylococcus aureus is a notorious pathogen highly successful at developing resistance to virtually all antibiotics to which it is exposed. Staphylococcal phage 2638A endolysin is a peptidoglycan hydrolase that is lytic for S. aureus when exposed externally, making it a new candidate antimicrobial. It shares a common protein organization with more than 40 other reported staphylococcal peptidoglycan hydrolases. There is an N-terminal M23 peptidase domain, a mid protein amidase 2 domain (N-acetylmuramoyl-L-alanine amidase), and a C-terminal SH3b cell wall-binding domain. It is the first phage endolysin reported with a secondary translational start site in the inter-lytic-domain region between the peptidase and amidase domains. Deletion analysis indicates that the amidase domain confers most of the lytic activity and requires the full SH3b domain for maximal activity. Although it is common for one domain to demonstrate a dominant activity over the other, the 2638A endolysin is the first in this class of proteins to have a high-activity amidase domain (dominant over the N-terminal peptidase domain). The high activity amidase domain is an important finding in the quest for high-activity staphylolytic domains targeting novel peptidoglycan bonds. PMID- 22777280 TI - Physiological heterogeneity of Pseudomonas taetrolens during lactobionic acid production. AB - Physiological heterogeneity constitutes a critical parameter in biotechnological systems since both metabolite yield and productivity are often hampered by the presence of undesired physiological cell subpopulations. In the present study, the physiological status and functionality of Pseudomonas taetrolens cells were monitored by multiparameter flow cytometry during fermentative lactobionic acid production at the shake-flask and bioreactor scale. In shake-flask fermentation, the onset of the lactobionic acid production phase was accompanied by a progressive loss of cellular metabolic activity, membrane polarization, and membrane integrity concomitantly to acidification. In fact, population dynamics has shown the prevalence of damaged and dead subpopulations when submitted to a pH < 4 from 16 h onwards. Furthermore, fluorescence-activated cell sorting revealed that these sublethally injured cells were nonculturable. In contrast, P. taetrolens cells exhibited a robust physiological status during bioreactor cultivations performed with a pH-shifted strategy at 6.5, remaining predominantly healthy and metabolically active (>96 %) as well as maintaining bioconversion efficiency throughout the course of the fermentation. Additionally, an assessment of the seed culture's physiological robustness was carried out in order to determine the best seed culture age. Results showed that bioreactor culture performance, growth, and lactobionic acid production efficiency were strongly dependent on the physiological heterogeneity displayed by the seed culture. This study provides the most suitable criteria for optimizing lactobionic acid production efficiency through a novel flow cytometric-based approach based on the physiological status of P. taetrolens. It also constitutes a valuable, broad ranging methodology for the enhancement of microbial bioprocesses involved in the production of secondary metabolites. PMID- 22777281 TI - Plant growth-promoting rhizobacteria affect the growth and nutrient uptake of Fraxinus americana container seedlings. AB - Plant growth-promoting rhizobacteria (PGPR) are important catalysts that regulate the functional properties of agricultural systems. However, there is little information on the effect of PGPR inoculation on the growth and nutrient accumulation of forest container seedlings. This study determined the effects of a growth medium inoculated with PGPR on the nutrient uptake, nutrient accumulation, and growth of Fraxinus americana container seedlings. PGPR inoculation with fertilizer increased the dry matter accumulation of the F. americana aerial parts with delayed seedling emergence time. Under fertilized conditions, the accumulation time of phosphorous (P) and potassium (K) in the F. americana aerial parts was 13 days longer due to PGPR inoculation. PGPR increased the maximum daily P and K accumulations in fertilized seedlings by 9.31 and 10.44 %, respectively, but had little impact on unfertilized ones. Regardless of fertilizer application, the root exudates, namely sugars, amino acids, and organic acids significantly increased because of PGPR inoculation. PGPR inoculation with fertilizer increased the root, shoot, and leaf yields by 19.65, 22.94, and 19.44 %, respectively, as well as the P and K contents by 8.33 and 10.60 %, respectively. Consequently, the N, P, and K uptakes increased by 19.85, 31.97, and 33.95 %, respectively. Hence, PGPR inoculation with fertilizer can be used as a bioenhancer for plant growth and nutrient uptake in forest container seedling nurseries. PMID- 22777282 TI - A vacuolar membrane protein affects drastically the biosynthesis of the ACV tripeptide and the beta-lactam pathway of Penicillium chrysogenum. AB - The knowledge about enzymes' compartmentalization and transport processes involved in the penicillin biosynthesis in Penicillium chrysogenum is very limited. The genome of this fungus contains multiple genes encoding transporter proteins, but very little is known about them. A bioinformatic search was made to find major facilitator supefamily (MFS) membrane proteins related to CefP transporter protein involved in the entry of isopenicillin N to the peroxisome in Acremonium chrysogenum. No strict homologue of CefP was observed in P. chrysogenum, but the penV gene was found to encode a membrane protein that contained 10 clear transmembrane spanners and two other motifs COG5594 and DUF221, typical of membrane proteins. RNAi-mediated silencing of penV gene provoked a drastic reduction of the production of the delta-(L-alpha-aminoadipyl L-cysteinyl-D-valine) (ACV) and isopenicillin N intermediates and the final product of the pathway. RT-PCR and northern blot analyses confirmed a reduction in the expression levels of the pcbC and penDE biosynthetic genes, whereas that of the pcbAB gene increased. Localization studies by fluorescent laser scanning microscopy using Dsred and GFP fluorescent fusion proteins and the FM 4-64 fluorescent dye showed clearly that the protein was located in the vacuolar membrane. These results indicate that PenV participates in the first stage of the beta-lactam biosynthesis (i.e., the formation of the ACV tripeptide), probably taking part in the supply of amino acids from the vacuolar lumen to the vacuole anchored ACV synthetase. This is in agreement with several reports on the localization of the ACV synthetase and provides increased evidence for a compartmentalized storage of precursor amino acids for non-ribosomal peptides. PenV is the first MFS transporter of P. chrysogenum linked to the beta-lactam biosynthesis that has been located in the vacuolar membrane. PMID- 22777284 TI - A practical route to long-chain non-natural alpha,omega-diamino acids. AB - An efficient method for the synthesis of long-chain alpha,omega-diamino acids, starting from natural alpha-amino acids, has been developed. The long-chain skeleton has been generated through condensation between a protected aldehyde, derived from L-aspartic acid, and an ylide obtained from an omega-hydroxy-alkyl phosphonium salt. After conversion of the omega-hydroxy group into an amine, catalytic hydrogenation produced the N,N'-protected alpha,omega-diamino acid. The present route to alpha,omega-diamino acids allows the modulation of the chain length depending on the length of the ylide used for the Wittig olefination reaction. PMID- 22777285 TI - Loss or major reduction of umami taste sensation in pinnipeds. AB - Umami is one of basic tastes that humans and other vertebrates can perceive. This taste is elicited by L-amino acids and thus has a special role of detecting nutritious, protein-rich food. The T1R1 + T1R3 heterodimer acts as the principal umami receptor. The T1R1 protein is encoded by the Tas1r1 gene. We report multiple inactivating (pseudogenizing) mutations in exon 3 of this gene from four phocid and two otariid species (Pinnipedia). Jiang et al. (Proc Natl Acad Sci U S A 109:4956-4961, 2012) reported two inactivating mutations in exons 2 and 6 of this gene from another otariid species. These findings suggest lost or greatly reduced umami sensory capabilities in these species. The widespread occurrence of a nonfunctional Tas1r1 pseudogene in this clade of strictly carnivorous mammals is surprising. We hypothesize that factors underlying the pseudogenization of Tas1r1 in pinnipeds may be driven by the marine environment to which these carnivorans (Carnivora) have adapted and may include: the evolutionary change in diet from tetrapod prey to fish and cephalopods (because cephalopods and living fish contain little or no synergistic inosine 5'-monophosphate that greatly enhances umami taste), the feeding behavior of swallowing food whole without mastication (because the T1R1 + T1R3 receptor is distributed on the tongue and palate), and the saltiness of sea water (because a high concentration of sodium chloride masks umami taste). PMID- 22777286 TI - Kidney cancer: lymphadenectomy for RCC-how many nodes? PMID- 22777288 TI - Prostate cancer: unravelling AR splice variant signalling in CPRC. PMID- 22777289 TI - Urinary tract infections: autophagy gene mutation confers protection against uropathogenic E. coli infection. PMID- 22777287 TI - Isolated, disseminated and circulating tumour cells in prostate cancer. AB - The loss of single cells from a tumour cell cluster marks an early event in the metastatic process of cancer progression. Although the metastatic cascade in prostate cancer is yet to be fully understood, monitoring circulating tumour cells (CTCs) and quantifying the load of tumour cell dissemination is currently being implemented into routine clinical practice for diagnosing minimal residual disease (MRD), estimating prognosis and monitoring treatment success. Current methods for enrichment of CTCs or disseminated tumour cells (DTCs) and detection of MRD rely on the expression of specific marker genes or proteins that might be altered during the process of tumour cell dissemination, therefore disrupting tumour cell detection. The tumour origin and malignant potential for metastasis of marker-positive cells is not yet clear. Some studies have demonstrated the potential of CTCs or DTCs as prognostic or predictive markers, leading to the increasing implementation of CTC measurement as an end point in clinical trials. PMID- 22777290 TI - Challenges in sexual medicine. AB - The sexual medicine field has been in mode of revolution until recently. Like all other fields of biomedical research, the economic situation around the world has had a negative impact on the field's momentum-research funding bodies, regulatory bodies and pharmaceutical companies seem to have placed sexual medicine in their low-priority list. But this is not the only challenge the field is facing. The successful development of phosphodiesterase type 5 (PDE5) inhibitors for treatment of erectile dysfunction (ED) means that research in this area seems to have slowed. However, there remain several unmet medical needs within sexual medicine such as premature ejaculation, severe ED and hypoactive sexual desire disorder, which await novel therapeutic approaches. Despite these challenges, research into finding and developing such therapies is likely to continue in the sexual medicine field, in an effort to improve the lives of our patients, who wait for effective therapies. PMID- 22777291 TI - Lysophospholipid acyltransferases: 1-acylglycerol-3-phosphate O acyltransferases. From discovery to disease. AB - PURPOSE OF REVIEW: Over the past several years, many more isoforms for the same enzymes, specifically for 1-acylglycerol-3-phosphate O-acyltransferases (AGPATs), have been cloned and studied. In this review, we summarize their biochemical features and discuss their functional role. RECENT FINDINGS: The most significant role of these AGPATs appeared from our observation of AGPAT2 in the biology of adipose tissue (adipocytes) in humans and mice. Other isoforms are shown to be implicated in lung, reproductive and cardiac muscle function and in the cause of cancer. In-vitro substrate specificities of these AGPATs also suggest the in-vivo role of these AGPATs in remodeling of several of the glycerophospholipids. SUMMARY: Despite significant progress in understanding the role of these AGPATs, much is still to be discovered in terms of how each of these AGPATs function in the presence or absence of other AGPATs and what their functional role might be. PMID- 22777292 TI - LOX-1: a multiligand receptor at the crossroads of response to danger signals. AB - PURPOSE OF REVIEW: LOX-1 is a multiligand receptor implicated in endothelial dysfunction and atherosclerosis, although it was originally identified as an oxidized LDL receptor. In this review, the roles of various LOX-1 ligands and their interaction with LOX-1 are discussed to understand the pathophysiological significance of LOX-1. RECENT FINDINGS: LOX-1 knockout mice showed resistance of endothelium-dependent vasorelaxation against oxidized LDL and retardation of atherosclerosis progression. LOX-1 ligand reduction in mice also attenuated atherosclerosis progression. In a human cohort study, high concentration of apoB containing LOX-1 ligands predicted the incidence of cardiovascular disease. Furthermore, modified HDL, which existed in high concentration in the plasma of coronary artery disease patients, was found to induce impairment of endothelial nitric oxide release via LOX-1. In addition to lipoproteins, LOX-1 was found to work as a C-reactive protein receptor providing a scaffold for the activation of the complement system. SUMMARY: LOX-1 is a unique molecule among the sensors of danger signals. LOX-1 is not only sensing danger signals such as modified LDL and heat shock protein, but also scaffolding other danger sensors including C reactive protein and C1q, and directly commanding responses to danger signals by working as a cell adhesion molecule. Via these functions, LOX-1 might work as a surveillance molecule of vascular homeostasis. PMID- 22777293 TI - Heme and haemoglobin direct macrophage Mhem phenotype and counter foam cell formation in areas of intraplaque haemorrhage. AB - PURPOSE OF REVIEW: Several studies have recently shown that haemoglobin drives a novel macrophage subset that is protected from foam cell formation. RECENT FINDINGS: In a previously overlooked area, two centres have independently shown that heme and haemoglobin drive an atheroprotective macrophage subset. We compare and contrast the approaches and findings of the laboratories and discuss some of the underlying biology and implications, concentrating on the aspects of lipidological relevance. SUMMARY: Treatments based on direct heme-mimetics or other agonists of this pathway have enormous potential for linked antioxidant protection via heme oxygenase 1 and reduced foam cell formation via liver X receptor, a potent combination for treating atherosclerosis. PMID- 22777294 TI - Optimising the delivery of tubulin targeting agents through antibody conjugation. AB - Despite their side effect profile, there currently remains a heavy reliance on traditional cytotoxics and particularly tubulin targeting agents in cancer chemotherapy. To address this concern, significant progress has been made in the selective delivery of drugs to the tumour site. This review will examine the published data in support of the hypothesis that forming antibody conjugates of tubulin targeting agents is an effective approach towards their more effective delivery to the tumour site. Particular emphasis will be placed on the diversity of concepts under investigation, the efficacy of resultant conjugates, evidence of decreased resistance and the side effect profiles of the conjugates. PMID- 22777295 TI - Prediction of the vitreal half-life of small molecular drug-like compounds. AB - PURPOSE: To build a fast, user-friendly computational model to predict the intravitreal half-lives of drug-like compounds. METHODS: We used multivariate analysis to build intravitreal half-life models using two data sets, one with experimental data derived from both pigmented and albino rabbits and another including only data from experiments with albino rabbits. RESULTS: The final models had a Q(2) value of 0.65 and 0.75 for the mixed and albino rabbit models, respectively. The models performed well in predicting the intravitreal half-life of an external test set. In addition, the models are physiologically interpretable, containing mainly hydrogen bonding and lipophilicity descriptors. CONCLUSION: The developed models enable reliable predictions of intravitreal half lives for use in the early drug development stages, without the need for prior experimental data. PMID- 22777296 TI - Response to growth hormone therapy in children with Noonan syndrome: correlation with or without PTPN11 gene mutation. AB - BACKGROUND/AIMS: The objective of this study was to evaluate the efficacy of recombinant human growth hormone (rhGH) therapy and the influence of genotype on the response to rhGH therapy in children with Noonan syndrome (NS). METHODS: 14 male and 4 female subjects with NS with short stature, whose height was < 3rd percentile, were included. The rhGH was subcutaneously administered at a dose of 66 MUg/kg/day. Mutations in the PTPN11 gene were identified in 10 subjects (55.6%). Mutations in the SOS1 (2 children, 11.1%), MEK1 (1 child, 5.6%) and KRAS (1 child, 5.6%) genes were also found. RESULTS: Height SDS increased from -2.8 +/ 0.9 at the start of rhGH therapy to -2.0 +/- 0.9 12 months later (p < 0.001). Height velocity increased from 5.0 +/- 0.9 cm/year in the year before treatment to 8.9 +/- 1.6 during treatment (p < 0.001). Changes in height SDS, height velocity, and serum IGF-1 level did not differ significantly between those children with or without PTPN11 mutations. CONCLUSION: The rhGH therapy significantly improved the growth velocity and increased the serum IGF-1 level. Longterm correlation between genotype and rhGH therapy responsiveness needs to be addressed in a large population. PMID- 22777297 TI - Chronicle of an unforetold death. PMID- 22777298 TI - Relationship between immunological parameters and the severity of neutropenia and effect of enteral nutrition on immune status during neoadjuvant chemotherapy on patients with advanced esophageal cancer. AB - OBJECTIVES: Chemotherapy may cause various toxicities as well as impair immunological function. However, little is known about the relationship between toxicities and immunological parameters or the effect of enteral nutrition (EN) on immunological status during chemotherapy. METHODS: 91 patients who received neoadjuvant chemotherapy (NACT) for esophageal cancer were randomly assigned to receive either EN or parenteral nutrition (PN). Immunological parameters, including total lymphocyte count (TLC), type 1 and type 2 CD4-positive T cells (Th1/Th2) balance, human leukocyte antigen (HLA)-DR expression on monocytes, natural killer cell activity, and phytohemagglutinin-stimulated lymphocyte proliferation were measured at baseline and day 14 of the first chemotherapy cycle. RESULTS: In the PN group, patients with grade 3-4 neutropenia showed significantly lower TLC, HLA-DR expression, and Th1/Th2 balance at day 14 compared to those with grade 0-2 neutropenia. Among pretherapeutic factors, Th1/Th2 balance was the only factor significantly associated with the severity of neutropenia. Concerning the comparison of immunological parameters between the EN and PN groups, HLA-DR expression at day 14 was significantly higher in the EN group. CONCLUSIONS: Baseline Th1/Th2 balance predicted the severity of neutropenia, and EN significantly reduced the decline of monocyte HLA-DR expression in patients with esophageal cancer receiving NACT. PMID- 22777300 TI - Activation of Pyrococcus furiosus alkaline phosphatase by divalent metal ions. AB - Treatment of a hyperthermophilic enzyme, alkaline phosphatase from Pyrococcus furiosus (PfuAP), with EDTA completely deactivated PfuAP, indicating that the presence of one or more divalent metal ions is essential for its catalytic activity. Subsequent addition of various divalent metal ions to the apoprotein recovered the enzymatic activity and, in particular, the addition of Co(II) resulted in an over 50-fold increase in activity compared with PfuAP before EDTA treatment. Intriguingly, PfuAP with Co(II) exhibited weaker stability toward heat treatment, suggesting that Co(2+) destabilizes the tertiary structure of PfuAP at high temperature. PMID- 22777302 TI - Vorapaxar expands antiplatelet options. Which patients may benefit from thrombin receptor antagonism? AB - Vorapaxar is the first substance of a new class of antiplatelet drugs that has been tested in large clinical trials. The protease-activated receptor 1 (PAR-1) antagonist inhibits thrombin-induced platelet activation to prevent atherothrombosis. In the phase 3 trials TRACER (acute coronary syndrome) and TRA 2P-TIMI 50 (stable atherosclerosis) reducing ischemic events with vorapaxar came at the cost of bleeding. TRACER compared vorapaxar to placebo in 12,944 patients who had non-ST-segment elevation acute coronary syndromes on top of contemporary treatment including dual antiplatelet therapy (aspirin and clopidogrel). Vorapaxar reduced ischemic events non-significantly, but increased bleeding significantly, therefore not justifying triple antiplatelet therapy in this setting. Follow-up was stopped early because of bleeding. TRA 2P-TIMI 50 examined 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease. Vorapaxar reduced ischemic events and increased bleeding both significantly. Recruitment of patients with prior stroke was stopped early. Net clinical outcome and subgroup analyses suggested that vorapaxar could be beneficial for patients with prior myocardial infarction - but no history of stroke. PMID- 22777303 TI - Vismodegib (Erivedge) for basal cell carcinoma. PMID- 22777304 TI - An imaging agent for amyloid. PMID- 22777301 TI - Novel bioactivity of NHERF1 in corneal neovascularization. AB - PURPOSE: This paper aimed to determine the involvement of Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) in experimental murine corneal neovascularization (NV), and to study the effect of NHERF1 on the biological properties of HUVEC and related mechanisms. METHODS: Using loss- and gain-function, we investigated the biological effects of NHERF1 on HUVEC. Western blotting was used to detect the expression of NHERF1 in cells. A carboxyfluorescein succinimidyl ester (CFSE) labeling assay and scarification test were used to measure the proliferation and migration activity, respectively, of HUVEC. The cell cycle distribution of the cells was assessed by flow cytometry analysis. The effect of NHERF1 on the phosphorylation levels of Akt and the changes of matrix metalloproteinase (MMP)-2 and MMP-9 levels were detected by western blotting analysis. Change in the NHERF1 expression in the alkali burn-induced corneal NV model was detected by microarray, real-time PCR, and immunofluorescence. RESULTS: Overexpression of exogenous NHERF1 in HUVEC slightly inhibited the proliferation and significantly reduced the migration of the cells. NHERF1 also significantly downregulated Akt1 phosphorylation induced by platelet-derived growth factor BB (PDGF-BB) and the secretion of MMP-2 and MMP-9 compared with control cells. NHERF1 was upregulated in corneas challenged with alkali burns. CONCLUSIONS: Our results indicated that NHERF1 might serve as a potential target for manipulating neovascularization related diseases. This discovery contributes to a better understanding of the bioactivity of NHERF1 in angiogenesis. PMID- 22777305 TI - Renal sympathetic denervation for hypertension. PMID- 22777306 TI - [Magnetic resonance elastography of the liver]. AB - CLINICAL/METHODICAL ISSUE: The early detection of liver fibrosis remains a major challenge in medical imaging. STANDARD RADIOLOGICAL METHODS: Nowadays staging of liver fibrosis is not a task for radiological examinations and the gold standard is liver puncture. METHODICAL INNOVATIONS: Elastography is sensitive to the mechanical properties of soft tissues and in the liver stiffness is highly correlated to the degree of fibrosis. In magnetic resonance imaging elastography (MRE) time-harmonic vibrations are induced in the liver and encoded by motion sensitive phase-contrast sequences. Viscoelastic constants are recovered from the obtained wave images and displayed by so-called elastograms. PERFORMANCE: The MRE procedure is able to discriminate low grades of fibrosis (F0-F1) from medium and severe fibrosis (F2-F4) with a diagnostic accuracy (AUROC) of 0.92. ACHIEVEMENTS: Currently, MRE is the most sensitive imaging modality for the noninvasive staging of liver fibrosis. PRACTICAL RECOMMENDATIONS: Current technical developments of MRE may further improve the accuracy of the method towards a new gold standard for noninvasive staging of fibrosis by radiologists. PMID- 22777307 TI - [Painless jaundice: a clear case?]. AB - A 44-year-old male patient presented with suddenly occurring first time painless jaundice. The patient history included whitish colored stools but no fever or weight loss. Imaging diagnostics and blood analysis revealed a strong suspicion of pancreatic disease. Histological examination showed dense plasma and lymphocellular infiltration and areas of fibrosis of the pancreatic parenchyma and confirmed the diagnosis of autoimmune pancreatitis which was successfully treated with immunosuppressive drugs. PMID- 22777308 TI - [Patient with swollen left cheek and otalgia]. PMID- 22777309 TI - Psychosocial factors associated with depression severity in pregnant adolescents. AB - Adolescent depression during pregnancy is associated with increased morbidity for the teen and her infant. This cross-sectional study explored the relationships among the independent histories of alcohol use, drug use, depression, and abuse (physical or sexual) on depression severity in a diverse group of 116 pregnant adolescents (mean age = 16) who attended an urban prenatal clinic. Ever having had an alcoholic drink was a significant predictor of higher depressive scores on Children's Depression Rating Scale-Revised, beta = 3.3 (0.8, 5.7); p < 0.05. History of abuse was associated with a significant 4.3-point higher mean depressive score, beta = 4.3 (1.8, 6.7), p < 0.001, and remained a statistically significant predictor of more severe depressive symptoms after adjustment for history of alcohol use, history of drug use, and history of depression. This study identified that a history of physical or sexual abuse is a significant factor related to the severity of depressive symptoms in pregnant adolescents, independent of a history of alcohol, drug use, or depression. These findings suggest that an assessment of history of alcohol use, as well as abuse history, may increase the likelihood of identifying adolescents at risk for antenatal depression. PMID- 22777311 TI - Should we improve the management of NSTEMI? Results from the population-based "acute myocardial infarction in Florence 2" (AMI-Florence 2) registry. AB - ST-segment and non-ST-segment elevation myocardial infarction (STEMI, NSTEMI) have opposite epidemiology, the latter being nowadays more common than the former. Consistently with these epidemiological trends, application of evidence based clinical practice guidelines on the management of NSTEMI should be promoted. We compared clinical features, hospital management and prognosis of STEMI/NSTEMI in an unselected cohort of 1,496 prospectively enrolled patients (STEMI, 36.9 % and NSTEMI, 63.1 %), admitted in 1 year to one of the six hospitals in Florence health district (Italy). Vital status was assessed after 1 year. NSTEMI patients were older, more often female, and affected by cardiovascular and non-cardiovascular comorbidities. Percutaneous coronary intervention (PCI) was performed more often in STEMI (82 %) than in NSTEMI patients (48 %, p < 0.001). Aspirin, clopidogrel, statins, beta-blockers, and ACE inhibitors were prescribed more frequently in STEMI. In-hospital mortality was significantly lower in NSTEMI than in STEMI (4.2 vs. 8.9 %, p < 0.001), even after adjusting for confounders in a multivariable logistic model (OR 0.27, 95 % CI 0.16-0.45). One-year mortality was similar in NSTEMI and STEMI patients in an unadjusted comparison (18.0 vs. 16.7 %, p = 0.51), but it was lower in NSTEMI patients in multivariable Cox analysis (HR 0.56, 95 % CI 0.42-0.75). PCI reduced the risk of 1-year mortality similarly in STEMI (HR 0.47, 95 % CI 0.28-0.79) and NSTEMI (HR 0.41, 95 % CI 0.28-0.60). PCI reduces mortality in both STEMI and NSTEMI, but it is underutilised in patients with NSTEMI. To improve overall prognosis of AMI, efforts should be made at improving the care of NSTEMI patients. PMID- 22777312 TI - Spontaneous renal artery dissection diagnosed by unenhanced magnetic resonance angiography: case report. AB - A 47-year-old patient is presented who was admitted to the emergency department with complaints of right-sided flank pain and hypertension. His creatinine and glomerular filtration rate were 2.5 mg/dl and 37 ml/min respectively, so that contrast media administration was contraindicated. The unenhanced magnetic resonance angiography image obtained with 3D in-flow inversion recovery sequence showed right renal artery dissection, without aortic dissection. Selective renal angiography confirmed the diagnosis and a stent was placed in the renal artery. The patient was free of pain after stenting, with normalized laboratory values and blood pressure. PMID- 22777313 TI - Composite type of split cord malformation: rare and difficult to explain. PMID- 22777314 TI - Malignant pleural mesothelioma in a patient with systemic sclerosis: the first report. AB - Malignant pleural mesothelioma (MPM) is a relatively rare but aggressive pleural tumor. Systemic sclerosis (SSc) is associated with the development of lung cancer and other malignancies. We describe a 58-year-old never-smoker female, previously diagnosed with limited cutaneous SSc, who presented with chest pain on the left side, dyspnea and circumferential nodular left pleural thickening. Fluorodeoxyglucose positron-emission tomography-computed tomography showed intense uptake in the thickened left pleura, mediastinal lymph nodes and left femur. Pleural fluid cytological examination along with nuclear and membranous positivity for Wilms tumor-1 antigen and epithelial membrane antigen on immunocytochemistry confirmed the diagnosis of MPM. To the best of our knowledge, this is the first report of MPM in a patient with SSc. PMID- 22777315 TI - Classification of chronic kidney disease biomarkers to predict coronary artery calcium. AB - BACKGROUND/AIMS: The link between CKD and CAC has been mostly established by studies of patients who have abnormally high phosphorus levels and advanced CKD or end-stage renal disease. The aim of this study was to examine if there are distinct trajectory classes of serum phosphorus (controlling for eGFR) that are associated CAC in a relatively healthy, community sample. METHODS: Phosphorus and eGFR were classified as a combined biomarker variable with 4 trajectory classes by growth mixture modeling. This classification variable was subsequently used to predict CAC as both a binary (i.e., onset) and continuous (i.e., accumulation) outcome using a two-part growth model. RESULTS: Membership in one class of phosphorus trajectory versus the next lowest level was associated with a 97.9 Agatston unit increase in CAC (p <.001). The magnitude of this finding is similar in size as some primary risk factors for cardiovascular disease, including a 55.3 Agatston unit (p <.001) increase associated with age, and a--75.1 Agatston unit (p <.001) decrease associated with female gender. CONCLUSIONS: Classification of phosphorus trajectories provides further definition for prediction of CAC within the conventional 'normal' range. Classifying trajectories may help determine clinically-relevant thresholds for interventions aimed at phosphorus reduction. PMID- 22777316 TI - Difference of antihypertensive prescribing between office- and hospital-based clinics in Taiwan. AB - BACKGROUND: The geographical location and medical facility may affect the pattern of antihypertensive prescriptions. Information regarding the correlation between the prescription and health care faculties in different geographical locations was lacking. OBJECTIVE: The aim of this study was to compare differences in the prescribing of antihypertensives between hospital-based clinics (hospital arm) and office-based clinics (office arm) in different geographical locations in Taiwan. METHOD: We collected data from the National Health Insurance database of Taiwan to carry out a population-based, retrospective cohort analysis of 3,218,794 patients newly diagnosed with hypertension in the period January 1, 1997 to December 31, 2004. Eligible participants were classified into either of two groups based on the level of health care faculty: hospital arm and office arm. The covariates composed of age, gender, antihypertensive regimens, urbanization status, comorbidity, and Charlson comorbidity index. RESULTS: There were 2,028,784 cases (63.0 %) for the hospital arm and 1,190,010 (37 %) for the office arm. In the hospital-based arm, there were 168,933 (8.3 %) patients diagnosed with diabetes mellitus, 166,110 (8.2 %) patients diagnosed with coronary artery disease, 147,465 (7.3 %) patients diagnosed with cerebrovascular accident, 86,866 (4.3 %) patients diagnosed with chronic kidney disease, 74,525 (3.7 %) patients diagnosed with benign prostatic hyperplasia, 55,517 (2.7 %) patients diagnosed with congestive heart failure. The all comorbidities in the hospital arm had significantly higher proportions than those in the office arm (p < 0.001). The Charlson comorbidity index in the hospital arm was higher than that in the office arm (p < 0.001). Physicians who practiced in the office arm prescribed polytherapy less often than those in the hospital arm (OR = 0.68, 95 % CI: 0.67-0.68). For overall urbanization status, the adjusted OR of polytherapy prescriptions in the aging city (OR = 1.08, 95 % CI: 1.05-1.12) was higher than other type cities. The highest urbanization-specific OR of polytherapy prescriptions was observed for highly urbanized city in the hospital arm (OR = 1.20, 95 % CI: 1.18-1.23) and aging city in the office arm (OR = 1.42, 95 % CI: 1.21-1.67). In the both arm, patients with lower CCI showed decreased risk of polytherapy prescription. CONCLUSION: The antihypertensive prescriptions in the clinical practices were different between the hospital arm and the office arm in the different health care, comorbidity, and urbanization status. During the study period, the proportion of antihypertensive polytherapy had declined. PMID- 22777317 TI - Preventable drug-related morbidity in community pharmacy: commentary on the implications for practice and policy of a novel intervention. AB - This commentary relates to a paper on the development and piloting of a risk management intervention in Portuguese community pharmacy, based on validated preventable drug-related morbidity indicators. In the paper we presented the research programme and implications for future evaluation. However, we believe that the intervention may be seen as important for patient safety without further evaluation. Therefore in this commentary we discuss considerations for service roll-out, by revisiting some issues already presented and by introducing aspects such as service definition and remuneration. We argue that in the absence of service remuneration, redesign of care processes through IT support and inter professional collaboration, and coaching to encourage the aforementioned efforts it is unlikely that the proposed risk management intervention will succeed in preventing drug-related morbidity. PMID- 22777318 TI - What's in a drop? Optimizing strategies for administration of drugs in pediatrics. AB - Accurate administration of drugs is an essential part of pharmacotherapy in children. Small differences in the amount of drugs administered, might evoke different clinical effects. This is especially of concern in drugs with a narrow therapeutic index. Guided by a case that was observed in pediatrics, some practical recommendations for the administration of oral drops in children are described. PMID- 22777319 TI - Communicating with physicians about medical decisions: a reluctance to disagree. PMID- 22777320 TI - Impact of histopathology on the outcome of D1/D2 gastrectomies with R0 resection. AB - AIMS: The primary objective of this study was to clarify the influence of histotype on the outcome of D1/D2 gastrectomized patients with pathologically proven R0 resection. The secondary objective was to demonstrate overall survival (OS), disease-free survival (DFS), and locoregional recurrence rates following standard curative surgery. PATIENTS AND METHODS: All patients had either pure signet-ring cell carcinoma (SRCC)/poorly differentiated adenocarcinoma (PDC) or moderately differentiated adenocarcinoma (MDC) of the stomach, preoperative radiologic evidence of locoregional disease, and no history of neoadjuvant therapy. Standards of surgical treatment were essentially based on the guidelines of the Japanese Research Society for the Study of Gastric Cancer. RESULTS: Between October 2003 and August 2010, seventy-eight patients were enrolled. Twenty-three patients underwent D1 dissection and 55 underwent D2 dissection. The OS and DFS rates were 33.2 +/- 5.9 months versus 31.5 +/- 4.3 months (p = 0.81) and 28.9 +/- 5.6 months vs. 29.3 +/- 4.4 months (p = 0.96) in the MDC and SRCC/PDC groups, respectively. Neither the extent of the operation (D1 vs. D2, p = 0.79) nor the histopathologic subtype of the primary tumor (MDC vs. SRCC/PDC, p = 0.91) influenced the OS and DFS. Multivariate logistic regression analysis disclosed pathologic stage (pTNM) as the only significant prognostic determinant of OS (p = 0.007) and DFS (p = 0.0003). CONCLUSION: Properly performed D1 and D2 dissection in our series resulted in a notable (6.4%) locoregional failure rate. In spite of the satisfactory locoregional control achieved by D1 and D2, there was no improvement in the survival figures of stage IIIA-B and IV gastric cancer patients. The histopathologic subtype of the primary tumor disclosed merely a statistical trend on the outcome measures of gastric cancer after curative surgery. PMID- 22777321 TI - Injury bounties: bad for sport, bad for players. PMID- 22777322 TI - ACSM clinician profile. PMID- 22777323 TI - Intramuscular ketorolac injections: the pregame Toradol parade. PMID- 22777325 TI - Common cause: are the cultural conditions for increasing physical activity and injury reduction mutualistic? PMID- 22777326 TI - Weightlifting's risky new trend: a case series of 41 insulin users. AB - Use of performance-enhancing drugs (PEDs) is common among strength-trained individuals, and a growing concern is the misuse of insulin. A 99-item Internet based survey was posted on discussion boards of various fitness, bodybuilding, weightlifting, and anabolic steroid Web sites between February and June 2009. A case series of 41 nondiabetic insulin users is described. The typical insulin user was 30.7 +/- 9.2 years old, male (97.6%), and Caucasian/white (86.8%) who classified himself as a "recreational exerciser" (47.5%). The average insulin user also used anabolic steroids (95.1%) and practiced polypharmacy by incorporating 16.2 +/- 5.6 PEDs in his or her yearly routine. Hypoglycemia was reported by most of the subjects (56.8%), and one individual reported unconsciousness. Insulin was obtained most commonly from local sources (e.g., friends, training partners, gym member/dealer; 40.5%) and community pharmacies (37.8%), with most (80.6%) finding it "easy" to acquire their insulin. Strategies aimed to prevent insulin misuse are needed. PMID- 22777327 TI - Effect of vitamin C supplements on physical performance. AB - Vitamin C is an essential component of the diet and may reduce the adverse effects of exercise-induced reactive oxygen species, including muscle damage, immune dysfunction, and fatigue. However, reactive oxygen species may mediate beneficial training adaptations that vitamin C attenuates; indeed, from a total of 12 studies, vitamin C in doses >1 g.d(-1) impaired sport performance substantially in four of four studies, possibly by reducing mitochondrial biogenesis, while a further four studies demonstrated impairments that were not statistically significant. Doses of ~0.2 g.d(-1) of vitamin C consumed through five or more servings of fruit and vegetables may be sufficient to reduce oxidative stress and provide other health benefits without impairing training adaptations. PMID- 22777328 TI - Effects of oral lactate consumption on metabolism and exercise performance. AB - Study of lactate metabolism has revealed that orally consumed lactate is used as an energy substrate either directly by oxidation or by conversion to glucose. Disposal of lactate by oxidation or gluconeogenesis consumes protons and can fortify blood bicarbonate levels temporarily and increase pH. These characteristics have led to investigations of lactate consumption as an energy substrate and as a buffering agent. Evidence has revealed no effects of lactate consumption on time to exhaustion during low- to moderate-intensity exercise, suggesting that it is ineffective as an energy supplement. Lactate ingestion has been shown to increase blood pH and bicarbonate levels and increase time to exhaustion in short, high-intensity work bouts. Future work should focus on determining optimal doses of lactate, temporal relationships between doses and exercise, and the efficacy of lactate as an ergogenic in different types of high intensity exercise. PMID- 22777329 TI - beta-Alanine supplementation. AB - beta-Alanine is rapidly developing as one of the most popular sport supplements used by strength/power athletes worldwide. The popularity of beta-alanine stems from its unique ability to enhance intramuscular buffering capacity and thereby attenuating fatigue. This review will provide an overview of the physiology that underlies the mechanisms of action behind beta-alanine, examine dosing schemes, and examine the studies that have been conducted on the efficacy of this supplement. In addition, the effect that beta-alanine has on body mass changes or whether it can stimulate changes in aerobic capacity also will be discussed. The review also will begin to explore the potential health benefits that beta-alanine may have on older adult populations. Discussion will examine the potential adverse effects associated with this supplement as well as the added benefits of combining beta-alanine with creatine. PMID- 22777330 TI - Exercise deficit disorder in youth: play now or pay later. AB - Although the benefits of regular physical activity are widely acknowledged, recent epidemiological findings indicate that a growing number of youth are not as active as they should be. The impact of a sedentary lifestyle during childhood and adolescence on lifelong pathological processes and associated health care costs has created a need for immediate action to manage, if not prevent, unhealthy behaviors during this vulnerable period of life. The concept of identifying children with exercise deficit disorder early in life and prescribing effective exercise interventions to prevent the cascade of adverse health outcomes later in life is needed to raise public awareness, focus on primary prevention, and impact the collective behaviors of health care providers, government officials, school administrators, public health agencies, and insurance companies. PMID- 22777331 TI - Putting the benefits and risks of aerobic exercise in perspective. AB - Although considerable epidemiologic and clinical evidence suggests that structured exercise, increased lifestyle activity, or both are cardioprotective, the absolute and relative risk of cardiovascular and musculoskeletal complications appear to increase transiently during vigorous physical activity. The estimated relative risk of exercise-related cardiac events ranges from 2.1 to 56 and is highest among habitually sedentary individuals with underlying cardiovascular disease who were performing unaccustomed vigorous physical exertion. Moreover, an estimated 7 million Americans receive medical attention for sports and recreation-related injuries each year. These risks, and their modulators, should be considered when endorsing strenuous leisure time or exercise interventions. If the current mantra "exercise is medicine" is embraced, underdosing and overdosing are possible. Thus, exercise may have a typical dose response curve with a plateau in benefit or even adverse effects, in some individuals, at more extreme levels. PMID- 22777332 TI - Resistance training is medicine: effects of strength training on health. AB - Inactive adults experience a 3% to 8% loss of muscle mass per decade, accompanied by resting metabolic rate reduction and fat accumulation. Ten weeks of resistance training may increase lean weight by 1.4 kg, increase resting metabolic rate by 7%, and reduce fat weight by 1.8 kg. Benefits of resistance training include improved physical performance, movement control, walking speed, functional independence, cognitive abilities, and self-esteem. Resistance training may assist prevention and management of type 2 diabetes by decreasing visceral fat, reducing HbA1c, increasing the density of glucose transporter type 4, and improving insulin sensitivity. Resistance training may enhance cardiovascular health, by reducing resting blood pressure, decreasing low-density lipoprotein cholesterol and triglycerides, and increasing high-density lipoprotein cholesterol. Resistance training may promote bone development, with studies showing 1% to 3% increase in bone mineral density. Resistance training may be effective for reducing low back pain and easing discomfort associated with arthritis and fibromyalgia and has been shown to reverse specific aging factors in skeletal muscle. PMID- 22777333 TI - Safety verification trials of mFOLFIRI and sequential IRIS + bevacizumab as first or second-line therapies for metastatic colorectal cancer in Japanese patients. AB - OBJECTIVE: S-1 is effective in sequential combination with irinotecan (IRIS) in treating metastatic colorectal cancer. We conducted a randomized phase II trial of modified leucovorin, fluorouracil and irinotecan (mFOLFIRI) + bevacizumab and sequential IRIS + bevacizumab as first- or second-line therapies. METHODS: Sixty metastatic colorectal cancer patients were randomly assigned to receive mFOLFIRI + bevacizumab or sequential IRIS + bevacizumab (7.5 mg/kg of bevacizumab and 150 mg/m(2) of irinitecan, and 80 mg/m(2)/day of S-1 orally from day 3 until day 16 as a 3-week course). The primary endpoint was the safety of each method until week 12, with the secondary endpoint being the comparison of the safety and efficacy of the two methods. RESULTS: The safety of the two treatments was comparable, except that G3 anorexia and diarrhoea were less frequent with sequential IRIS + bevacizumab. The overall response rate was 62% [95% confidence interval (CI) 40.1-79.8] versus 72% (95% CI 50.6-86.2), and progression-free survival was 324 days (95% CI 247-475) versus 345 days (95% CI 312-594) with mFOLFIRI + bevacizumab versus IRIS + bevacizumab, respectively. CONCLUSION: Sequential IRIS + bevacizumab is a safe and effective method of systemic chemotherapy against metastatic colorectal cancer and is compatible with mFOLFIRI + bevacizumab. PMID- 22777334 TI - Pharmacokinetic modelling of N-(4-[(18)F]fluorobenzoyl)interleukin-2 binding to activated lymphocytes in an xenograft model of inflammation. AB - PURPOSE: N-(4-[(18)F]Fluorobenzoyl)interleukin-2 ([(18)F]FB-IL2) specifically binds to interleukin-2 receptors (IL-2R) and thus may be used to detect inflammation processes using positron emission tomography (PET). We now validated whether [(18)F]FB-IL2 can be used to quantify activated human peripheral blood mononuclear cells (hPBMC) in rats by pharmacokinetic modelling. METHODS: Eleven Wistar rats were subcutaneously inoculated in the shoulder with different amounts of phytohaemagglutinin (PHA) activated hPBMC 15 min before i.v. injection of [(18)F]FB-IL2. A 60-min dynamic PET scan was acquired and arterial blood sampling and metabolite analysis were performed. At the end of the scan, animals were terminated and the inflammatory lesion dissected. PET data were analysed using Logan and Patlak analysis as well as one-tissue and two-tissue compartment models. Model preferences according to the Akaike information criterion (AIC) and correlation between PET measurements and the number of CD25-positive cells were evaluated. RESULTS: A high correlation between ex vivo tracer uptake (standardized uptake value) in the xenograft and the number of inoculated CD25 positive cells was observed (R (2) = 0.90). Plasma time-activity curves showed a rapid washout of the radiopharmaceutical from blood, while the time-activity curves of the inflammatory lesions showed slower washout. Time-activity curves could be fitted well by the Logan analysis method, indicating that the binding between [(18)F]FB-IL2 and CD25 is reversible. AIC indicated that data could be modelled best by a two-tissue reversible compartment model. A high correlation was observed between the binding potential and the number of CD25-positive cells (R (2) = 0.876, p < 0.0001). Based on binding potential measured by PET, the limit of detection was about 160,000 CD25-positive cells per 200 MUl lesion (95 % confidence). CONCLUSION: [(18)F]FB-IL2 kinetics in this animal model of inflammation could be best described by a reversible two-tissue compartment model. The [(18)F]FB-IL2 binding potential is a suitable measure for accurate quantification of lymphocytic infiltration in pathological conditions with PET. PMID- 22777335 TI - Diagnostic and prognostic correlates of preoperative FDG PET for breast cancer. AB - PURPOSE: To explore the preoperative utility of FDG PET for the diagnosis and prognosis in a retrospective breast cancer case series. METHODS: In this retrospective study, 104 patients who had undergone a preoperative FDG PET scan for primary breast cancer at the UZ Brussel during the period 2002-2008 were identified. Selection criteria were: histological confirmation, FDG PET performed prior to therapy, and breast surgery integrated into the primary therapy plan. Patterns of increased metabolism were recorded according to the involved locations: breast, ipsilateral axillary region, internal mammary chain, or distant organs. The end-point for the survival analysis using Cox proportional hazards was disease-free survival. The contribution of prognostic factors was evaluated using the Akaike information criterion and the Nagelkerke index. RESULTS: PET positivity was associated with age, gender, tumour location, tumour size >2 cm, lymphovascular invasion, oestrogen and progesterone receptor status. Among 63 patients with a negative axillary PET status, 56 (88.9 %) had three or fewer involved nodes, whereas among 41 patients with a positive axillary PET status, 25 (61.0 %) had more than three positive nodes (P < 0.0001). In the survival analysis of preoperative characteristics, PET axillary node positivity was the foremost statistically significant factor associated with decreased disease-free survival (hazard ratio 2.81, 95% CI 1.17-6.74). CONCLUSION: Preoperative PET axillary node positivity identified patients with a higher burden of nodal involvement, which might be important for treatment decisions in breast cancer patients. PMID- 22777337 TI - The performance of process measures in hepatitis C. AB - OBJECTIVES: Previous evaluations regarding the extent to which standard chronic hepatitis C virus (HCV) care processes are delivered during routine clinical care are scant and have primarily relied on automated data--the validity of which is unknown. METHODS: We examined adherence to 24 explicit modified Delphi panel derived HCV-specific process measures in a cohort of 122,744 patients enrolled in the automated Veterans Administration HCV Clinical Case Registry between 2000 and 2006. We reviewed medical charts of 717 patients to compare the agreement between Registry and charts. We also estimated the effect of justifiable exceptions on measured performance in HCV by determining the proportion of patients who failed a measure but met a valid exception (i.e., patient refusal, outside care, or treatment contraindications). RESULTS: The percentage of patients who met the individual measures varied. For example, 74% of patients received HCV genotype testing, 23% received antiviral treatment, 28% received liver biopsy, and 16% received hepatitis A vaccination. We found excellent agreement between the Registry and charts in all measures (agreement coefficients >0.75). However, exceptions to indicated care documented in charts were common for genotype testing, liver biopsy, and antiviral treatment. After accounting for these exceptions, the measure rates increased from 75 to 93% for genotype testing, 31 to 50% for liver biopsy, and from 26 to 64% for antiviral treatment. Treatment contraindications were the most common reasons for not meeting indicated care. CONCLUSIONS: Automated data missed several exceptions to care that are documented only in providers' notes, thus underestimating process of care. These results have implications for future quality assessment initiatives-most of which will likely rely on automated data for process-based quality reporting. After accounting for automated data and medical record reviews, vaccinations and antiviral treatment rates in the Veterans Administration left room for improvement. PMID- 22777336 TI - The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based study [corrected] from the Canadian Multicentre Osteoporosis Study (CaMos). AB - OBJECTIVES: Proton pump inhibitor (PPI) use has been identified as a risk factor for hip and vertebral fractures. Evidence supporting a relationship between PPI use and osteoporosis remains scant. Demonstrating that PPIs are associated with accelerated bone mineral density (BMD) loss would provide supportive evidence for a mechanism through which PPIs could increase fracture risk. METHODS: We used the Canadian Multicentre Osteoporosis Study data set, which enrolled a population based sample of Canadians who underwent BMD testing of the femoral neck, total hip, and lumbar spine (L1-L4) at baseline, and then again at 5 and 10 years. Participants also reported drug use and exposure to risk factors for osteoporosis and fracture. Multivariate linear regression was used to determine the independent association of PPI exposure and baseline BMD, and on change in BMD at 5 and 10 years. RESULTS: In all, 8,340 subjects were included in the baseline analysis, with 4,512 (55%) undergoing year 10 BMD testing. After adjusting for potential confounders, PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip. PPI use was not associated with a significant acceleration in covariate-adjusted BMD loss at any measurement site after 5 and 10 years of follow-up. CONCLUSIONS: PPI users had lower BMD at baseline than PPI non-users, but PPI use over 10 years did not appear to be associated with accelerated BMD loss. The reasons for discordant findings between PPI use at baseline and during follow-up require further study. PMID- 22777338 TI - Diagnostic utility of major basic protein, eotaxin-3, and leukotriene enzyme staining in eosinophilic esophagitis. AB - OBJECTIVES: Features of eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) overlap. We aimed to determine whether staining for tissue biomarkers would differentiate EoE from GERD, suggesting utility for diagnosis of EoE. METHODS: In this case-control study, EoE patients defined by consensus guidelines were compared to GERD patients with eosinophils on esophageal biopsy. Immunohistochemistry was performed for major basic protein (MBP), eotaxin-3, leukotriene A4 hydrolase (LTA4H), and leukotriene C4 synthase (LTC4S). After masking, the maximum staining density (cells per mm(2)) was quantified for each marker and compared between groups. Receiver operator characteristic curves were constructed, and the area under the curve (AUC) calculated to assess the diagnostic utility of each of the biomarkers alone and in combination with eosinophil counts. RESULTS: There were 51 EoE cases (mean age 24; mean 143 eosinophils per high-power field (eos per h.p.f.)) and 54 GERD controls (mean age 34; mean 20 eos per h.p.f.). The MBP density was higher in EoE than in GERD (1479 vs. 59 cells per mm(2); P<0.001), as was the eotaxin-3 density (2219 vs. 479; P<0.001). There were no differences for LTA4H and LTC4S. MBP density and eosinophil count correlated (R=0.81; P<0.001); correlation with eotaxin-3 was weaker (R=0.25; P=0.01). The AUC for diagnosis of EoE was 0.96 for MBP, 0.87 for eotaxin-3, 0.58 for LTA4H, 0.66 for LTC4S, and 0.99 for the combination of MBP, eotaxin-3, and eosinophil count. CONCLUSIONS: Patients with EoE had substantially higher levels of MBP and eotaxin-3 staining than GERD patients. These markers may have utility as a diagnostic assay for EoE. PMID- 22777339 TI - Concomitant symptoms itemized in the Reflux Disease Questionnaire are associated with attenuated heartburn response to acid suppression. AB - OBJECTIVES: The Reflux Disease Questionnaire (RDQ) contains six symptom items for diagnosing and gauging gastroesophageal reflux disease (GERD) severity. However, clinical trials have generally focused only on the "substernal burning" item and limited data exist on the effect of concomitant items on the treatment response of "substernal burning". METHODS: Data from two large randomized trials of AZD0865 25-75 mg/day vs. esomeprazole 20 or 40 mg/day in patients with GERD defined by moderate to severe (>= 4 days per week) "substernal burning" (non erosive reflux disease (NERD), N = 1,460; reflux esophagitis (RE), N = 1,514) were re-analyzed. As no differences were found between drugs or doses in treatment response of "substernal burning", pooled data were used to determine the impact of additional RDQ items on the response of "substernal burning" to acid suppression. RESULTS: At baseline, patients reported an average of four RDQ items. "Substernal burning" was the most responsive to therapy in the 3.3% of individuals with this as their only baseline RDQ symptom. The report of any other RDQ item was associated with a reduction in the responsiveness of "substernal burning" to acid suppression (e.g., RE patients with high severity "dyspepsia pain" had an odds ratio of 0.20 for an improvement in "substernal burning" to treatment). CONCLUSIONS: Other concomitant RDQ items, particularly "substernal pain" or "dyspepsia-pain", were associated with a reduced treatment effect of acid suppression on "substernal burning". These findings support the use of a more comprehensive assessment of disease state and treatment response in GERD trials and clinical practice. PMID- 22777340 TI - A prospective study of cigarette smoking and the risk of inflammatory bowel disease in women. AB - OBJECTIVES: Long-term data on the influence of cigarette smoking, especially cessation, on the risk of Crohn's disease (CD) and ulcerative colitis (UC) are limited. METHODS: We conducted a prospective study of 229,111 women in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II). Biennially, we collected updated data on cigarette smoking, other risk factors, and diagnoses of CD or UC confirmed by medical record review. RESULTS: Over 32 years in NHS and 18 years in NHS II, we documented 336 incident cases of CD and 400 incident cases of UC. Compared with never smokers, the multivariate hazard ratio (HR) of CD was 1.90 (95% confidence interval (CI), 1.42-2.53) among current smokers and 1.35 (95% CI, 1.05-1.73) among former smokers. Increasing pack-years was associated with increasing risk of CD (Ptrend < 0.0001), whereas smoking cessation was associated with an attenuation of risk. By contrast, the multivariate HR of UC was 0.86 (95% CI, 0.61-1.20) among current smokers and 1.56 (95% CI, 1.26-1.93) among former smokers. The risk of UC was significantly increased within 2-5 years of smoking cessation (HR, 3.06; 95% CI, 2.00-4.67) and remained persistently elevated over 20 years. CONCLUSIONS: Current smoking is associated with an increased risk of CD, but not UC. By contrast, former smoking is associated with an increased risk of UC, with risk persisting over two decades after cessation. PMID- 22777341 TI - Diverticular disease as a chronic illness: evolving epidemiologic and clinical insights. AB - Diverticular disease imposes a significant burden on Western and industrialized societies. The traditional pathogenesis model posits that low dietary fiber predisposes to diverticulosis, and fecalith obstruction prompts acute diverticulitis that is managed with broad-spectrum antibiotics or surgery. However, a growing body of knowledge is shifting the paradigm of diverticular disease from an acute surgical illness to a chronic bowel disorder composed of recurrent abdominal symptoms and considerable psychosocial impact. New research implicates a role for low-grade inflammation, sensory-motor nerve damage, and dysbiosis in a clinical picture that mimics irritable bowel syndrome (IBS) and even inflammatory bowel disease (IBD). Far from being an isolated event, acute diverticulitis may be the catalyst for chronic symptoms including abdominal pain, cramping, bloating, diarrhea, constipation, and "post-diverticulitis IBS." In addition, studies reveal lower health-related quality of life in patients with chronic diverticular disease vs. controls. Health-care providers should maintain a high index of suspicion for the multifaceted presentations of diverticular disease, and remain aware that it might contribute to long-term emotional distress beyond traditional diverticulitis attacks. These developments are prompting a shift in therapeutic approaches from widespread antimicrobials and supportive care to the use of probiotics, mesalamine, and gut-directed antibiotics. This review addresses the emerging literature regarding epidemiology, pathophysiology, and management of chronic, symptomatic diverticular disease, and provides current answers to common clinical questions. PMID- 22777342 TI - Mechanisms of increased gastroesophageal reflux in patients with cystic fibrosis. AB - OBJECTIVES: Up to 80% of patients with cystic fibrosis (CF) may have increased gastroesophageal reflux (GER). It has been suggested that increased GER is due to low basal lower esophageal sphincter (LES) pressure and a high number of transient LES relaxations (TLESRs). The aim of our study was to reassess the mechanisms of GER in adult CF patients using state of the art upper gastrointestinal physiology techniques: high-resolution manometry impedance (HRM MII). METHODS: We studied 12 CF patients (age 32 range (19-58), 5 males/7 females) and 11 age-matched healthy volunteers (age 27 range (20-36), 4 males /7 females). HRM-MII was performed in a semi-recumbent position for 30 min during fasting and for 2 h after a standard meal (1,000 kcal). We measured total reflux and proximal extent of reflux with impedance; basal LES pressure, TLESRs, and gastroesophageal pressure gradient (GEPG) with HRM. RESULTS: Basal LES pressure was lower in CF patients compared with healthy controls, both in the pre- and postprandial period (preprandial 13 (7-22) vs. 24 (13-26) mm Hg, P = 0.04; postprandial 10 (8-14) vs. 18 (10-31) mm Hg, P = 0.01) and TLESRs were the main mechanism for reflux both in CF and in controls. We could not find a difference in the number of TLESRs in CF patients compared with healthy (14 (10-20) vs. 13 (10-24), P = not significant). However, reflux during TLESRs was more frequent in CF compared with healthy volunteers (80 (70-95) vs. 42 (20-78) %, P = 0.0058). GEPG during TLESRs was significantly higher in CF than in controls during inspiration (13.5 (9.5-15.8) vs. 7 (4-9.9) mm Hg, P = 0.004). This difference was due to a lower inspiratory intra-thoracic pressure in CF patients (-8.2 (-10.2-( 4.6) vs. -0.08 (-5.7-2.7) mm Hg, P = 0.002). Compared with controls, CF patients had significantly higher number of reflux episodes (13 (6-20) vs. 7 (3-9), P = 0.014) and CF patients also showed a higher proportion of reflux episodes with a high proximal extent compared with healthy volunteers (49 (22-50) vs. 0 (0-17) %, P = 0.0028). CONCLUSIONS: CF patients have increased GER with a high proximal extent. Although we could not find a higher number of TLESRs in CF, there is a higher proportion of TLESRs associated with reflux. Unlike non-CF GER disease patients (with increased intra-abdominal pressure), reflux during TLESRs in CF is probably due to an increased GEPG mainly generated by a greater inspiratory negative intra-thoracic pressure. PMID- 22777343 TI - Occurrence of 4-tert-butylphenol (4-t-BP) biodegradation in an aquatic sample caused by the presence of Spirodela polyrrhiza and isolation of a 4-t-BP utilizing bacterium. AB - Although 4-tert-butylphenol (4-t-BP) is a serious aquatic pollutant, its biodegradation in aquatic environments has not been well documented. In this study, 4-t-BP was obviously and repeatedly removed from water from four different environments in the presence of Spirodela polyrrhiza, giant duckweed, but 4-t-BP persisted in the environmental waters in the absence of S. polyrrhiza. Also, 4-t BP was not removed from autoclaved pond water with sterilized S. polyrrhiza. These results suggest that the 4-t-BP removal from the environmental waters was caused by biodegradation stimulated by the presence of S. polyrrhiza rather than by uptake by the plant. Moreover, Sphingobium fuliginis OMI capable of utilizing 4-t-BP as a sole carbon and energy source was isolated from the S. polyrrhiza rhizosphere. Strain OMI degraded 4-t-BP via a meta-cleavage pathway, and also degraded a broad range of alkylphenols with linear or branched alkyl side chains containing two to nine carbon atoms. Root exudates of S. polyrrhiza stimulated 4 t-BP degradation and cell growth of strain OMI. Thus, the stimulating effects of S. polyrrhiza root exudates on 4-t-BP-degrading bacteria might have contributed to 4-t-BP removal in the environmental waters with S. polyrrhiza. These results demonstrate that the S. polyrrhiza-bacteria association may be applicable to the removal of highly persistent 4-t-BP from wastewaters or polluted aquatic environments. PMID- 22777344 TI - Dissecting the dimerization motif of Enterococcus hirae's Zn(II)CopY. AB - The regulation of the copper homeostasis pathway in Enterococcus hirae is conducted through activity of the zinc metalloprotein Zn(II)CopY, which is a Cu(I)-responsive dimeric repressor (Cobine et al., Biochemistry 41:5822-5829, 2002). Its dimerization domain contains a C-terminal cysteine-rich metal-binding motif used for Cu(I) sensing adjacent to an aliphatic-rich repeating sequence, but it is unclear as to which regions contribute most to the interaction. To accomplish this, a synthetically produced CopY construct (CDG) was fused with solubility enhancement tags so the key components of the elements of the aliphatic repeat and metal-binding site could be probed for their dimerization activity. The resultant fusion constructs were tested using two independent methods. Isothermal titration calorimetry, an in vitro technique, was employed to determine dimer affinity thermodynamically. Protein fragment complementation, an in vivo technique, made it possible to rapidly screen homodimeric and heterodimeric complexes within live cells. The combination of in vivo and in vitro studies enabled the identification of CDG sequences that dimerize and sequences that do not, in addition to deciphering relative dimer affinity between all constructs screened. The in vivo technique allowed the formation of heterodimers to be tested for their ability to form specific complexes between dissimilar CDG analogs. PMID- 22777345 TI - Remarkable heterogeneity in myosin heavy-chain composition of the human young masseter compared with young biceps brachii. AB - Adult human jaw muscles differ from limb and trunk muscles in enzyme histochemical fibre type composition. Recently, we showed that the human masseter and biceps differ in fibre type pattern already at childhood. The present study explored the myosin heavy-chain (MyHC) expression in the young masseter and biceps muscles by means of gel electrophoresis (GE) and immuno-histochemical (IHC) techniques. Plasticity in MyHC expression during life was evaluated by comparing the results with the previously reported data for adult muscles. In young masseter, GE identified MyHC-I, MyHC-IIa MyHC-IIx and small proportions of MyHC-fetal and MyHC-alpha cardiac. Western blots confirmed the presence of MyHC I, MyHC-IIa and MyHC-IIx. IHC revealed in the masseter six isomyosins, MyHC-I, MyHC-IIa, MyHC-IIx, MyHC-fetal, MyHC alpha-cardiac and a previously not reported isoform, termed MyHC-IIx'. The majority of the masseter fibres co-expressed two to four isoforms. In the young biceps, both GE and IHC identified MyHC-I, MyHC IIa and MyHC-IIx. MyHC-I predominated in both muscles. Young masseter showed more slow and less-fast and fetal MyHC than the adult and elderly masseter. These results provide evidence that the young masseter muscle is unique in MyHC composition, expressing MyHC-alpha cardiac and MyHC-fetal isoforms as well as hitherto unrecognized potential spliced isoforms of MyHC-fetal and MyHC-IIx. Differences in masseter MyHC expression between young adult and elderly suggest a shift from childhood to adulthood towards more fast contractile properties. Differences between masseter and biceps are proposed to reflect diverse evolutionary and developmental origins and confirm that the masseter and biceps present separate allotypes of muscle. PMID- 22777346 TI - Fibroblast growth factor receptor 3 is highly expressed in rarely dividing human type A spermatogonia. AB - Human spermatogonia (Spg) and their fetal precursors express fibroblast growth factor receptor 3 (FGFR3). To further elucidate the role of FGFR3 in the control of Spg self-renewal, proliferation, and/or differentiation, and to narrow down the FGFR3-positive cell type(s) in the normal adult human testis, tissue sections and whole mount preparations of seminiferous tubules were analyzed combining immunofluorescence and confocal fluorescence microscopy. FGFR3 protein was chiefly observed in cellular membranes and cytoplasmic vesicles of a subpopulation of type A Spg, which comprised the chromatin rarefaction zone containing type A(dark). Cytoplasmic expression of FGFR3 and nuclear expression of proliferation-associated antigen KI-67 were mutually exclusive. Similarly, FGFR3-positive Spg were negative for Doublesex and Mab-3 related transcription factor 1 (DMRT1). By contrast, undifferentiated embryonic cell transcription factor 1 (UTF1) and survival time-associated PHD finger in ovarian cancer 1 protein (SPOC1) were co-expressed in the nuclei of FGFR3-positive Spg. Whole mounted seminiferous tubules illustrated the clonogenic arrangement of the FGFR3/UTF1 double-positive Spg, which mainly occurred as pairs or quadruplets and, different from the KIT-positive Spg, showed no overlap with KI-67 labeled clusters. Taken together, in the adult human testis, FGFR3 expression is a feature of small clones of rarely dividing type A Spg which resemble "undifferentiated" Spg, including the spermatogonial stem cells. PMID- 22777348 TI - Germline mutation of Brca1 alters the fate of mammary luminal cells and causes luminal-to-basal mammary tumor transformation. AB - Breast cancer developed in familial BRCA1 mutation carriers bears striking similarities to sporadic basal-like breast tumors. The mechanism underlying the function of BRCA1 in suppressing basal-like breast cancer remains unclear. We previously reported that the deletion of p18(Ink4c) (p18), an inhibitor of G1 cyclin Ds-dependent CDK4 and CDK6, stimulates mammary luminal progenitor cell proliferation and leads to spontaneous luminal tumor development. We report here that germline mutation of Brca1 in p18-deficient mice blocks the increase of luminal progenitor cells, impairs luminal gene expression and promotes malignant transformation of mammary tumors. Instead of the luminal mammary tumors developed in p18 single-mutant mice, mammary tumors developed in the p18;Brca1 mice, similar to breast cancer developed in familial BRCA1 carriers, exhibited extensive basal-like features and lost the remaining wild-type allele of Brca1. These results reveal distinct functions of the RB and BRCA1 pathways in suppressing luminal and basal-like mammary tumors, respectively. These results also suggest a novel mechanism--causing luminal-to-basal transformation--for the development of basal-like breast cancer in familial BRCA1 carriers and establish a unique mouse model for developing therapeutic strategies to target both luminal and basal-like breast cancers. PMID- 22777347 TI - "Tasting" the airway lining fluid. AB - Specialized epithelial cells of the respiratory tract have been termed "solitary chemosensory cells" based upon the expression of components of the canonical sweet, umami and bitter taste transduction pathway, or "brush cells" based upon their characteristic morphological feature, i.e. an apical, brush-like tuft of rigid, villin containing microvilli. Cells defined by these criteria might not match one-to-one, and a generally accepted terminology is still lacking. With respect to cellular shape, ultrastructure, expression of elements of the taste transduction cascade, innervation and synapse formation, and effects evoked upon their stimulation, it appears that chemosensory/brush in the upper respiratory tract (nasal respiratory mucosa, vomeronasal duct, auditory tube), in the olfactory mucosa, in the larynx, in the lower airways (trachea, bronchi) and in the alveolar region (rat only) each represent distinct groups. Still, they have in common to monitor the chemical composition of the mucosal lining fluid. They serve as sentinels detecting bacterial colonization or the presence of other harmful components in the mucosal lining fluid, leading to the initiation of avoidance reflexes and/or local defense mechanisms which are adapted to their anatomical localization. Free nerve endings are also responsive to inhaled irritants and further work will be needed to discriminate between the contributions of such nerve endings and chemosensory cells in chemical monitoring and defense initiation. Interestingly, there is first emerging evidence that respiratory chemosensory cells may respond to more than one canonical taste quality so that they, in analogy to polymodal nociceptors, may serve as polymodal chemosensors of potentially dangerous signals. PMID- 22777349 TI - PGC-1beta mediates adaptive chemoresistance associated with mitochondrial DNA mutations. AB - Primary mitochondrial dysfunction commonly leads to failure in cellular adaptation to stress. Paradoxically, however, nonsynonymous mutations of mitochondrial DNA (mtDNA) are frequently found in cancer cells and may have a causal role in the development of resistance to genotoxic stress induced by common chemotherapeutic agents, such as cis-diammine-dichloroplatinum(II) (cisplatin, CDDP). Little is known about how these mutations arise and the associated mechanisms leading to chemoresistance. Here, we show that the development of adaptive chemoresistance in the A549 non-small-cell lung cancer cell line to CDDP is associated with the hetero- to homoplasmic shift of a nonsynonymous mutation in MT-ND2, encoding the mitochondrial Complex-I subunit ND2. The mutation resulted in a 50% reduction of the NADH:ubiquinone oxidoreductase activity of the complex, which was compensated by increased biogenesis of respiratory chain complexes. The compensatory mitochondrial biogenesis was most likely mediated by the nuclear co-activators peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) and PGC 1beta, both of which were significantly upregulated in the CDDP-resistant cells. Importantly, both transient and stable silencing of PGC-1beta re-established the sensitivity of these cells to CDDP-induced apoptosis. Remarkably, the PGC-1beta mediated CDDP resistance was independent of the mitochondrial effects of the co activator. Altogether, our results suggest that partial respiratory chain defects because of mtDNA mutations can lead to compensatory upregulation of nuclear transcriptional co-regulators, in turn mediating resistance to genotoxic stress. PMID- 22777350 TI - Identification of ribosomal protein S25 (RPS25)-MDM2-p53 regulatory feedback loop. AB - There is an increasing interest in determining the role of ribosomal proteins (RPs) in the regulation of MDM2-p53 pathway in coordinating cellular response to stress. Herein, we report a novel regulatory role of ribosomal protein S25 (RPS25) in MDM2-mediated p53 degradation and a feedback regulation of S25 by p53. We demonstrated that S25 interacted with MDM2 and inhibited its E3 ligase activity, resulting in the reduction of MDM2-mediated p53 ubiquitination and the stabilization and activation of p53. S25, MDM2 and p53 formed a ternary complex following ribosomal stress. The nucleolar localization and MDM2-binding domains of S25 were critical for its role in MDM2-mediated p53 regulation. Knockdown of S25 by siRNA attenuated the induction and activation of p53 following ribosomal stress. S25 stabilized and cooperated with MDMX to regulate MDM2 E3 ligase activity. Furthermore, S25 was identified to be a transcriptional target of p53; p53 directly bound to S25 promoter and suppressed S25 expression. Our results suggest that there is a S25-MDM2-p53 regulatory feedback loop, which may have an important role in cancer development and progression. PMID- 22777351 TI - Autophagy restricts proliferation driven by oncogenic phosphatidylinositol 3 kinase in three-dimensional culture. AB - Autophagy is a tightly regulated lysosomal self-digestion process that can both promote and impede tumorigenesis. Here, we utilize a three-dimensional (3D) culture model to address how interactions between autophagy and the phosphatidylinositol 3-kinase(PI3K)/Akt/mammalian target of rapamycin pathway impact the malignant behavior of cells carrying a tumor-derived, activating mutation in PI3K (PI3K-H1047R). In this model, autophagy simultaneously mediates tumor-suppressive and -promoting functions within individual glandular structures. In 3D culture, constitutive PI3K activation overcomes proliferation arrest and promotes resistance to anoikis in the luminal space, resulting in aberrant structures with filled lumen. Inhibiting autophagy in PI3K-H1047R structures triggers luminal cell apoptosis, resulting in lumen clearance. At the same time, autophagy gene depletion strongly enhances PI3K-H1047R cell proliferation during 3D morphogenesis, revealing an unexpected role for autophagy in restricting proliferation driven by PI3K activation. Intriguingly, overexpression of the autophagy cargo receptor p62/SQSTM1 in PI3K-H1047R cells is sufficient to enhance cell proliferation, activate the extracellular signal related kinase/mitogen-activated protein kinase pathway and to promote epidermal growth factor-independent proliferation in 3D culture. Overall, these results indicate that autophagy antagonizes specific aspects of oncogenic PI3K transformation, with the loss of autophagy promoting proliferation. PMID- 22777352 TI - Arg/Abl2 promotes invasion and attenuates proliferation of breast cancer in vivo. AB - Tumor progression is a complex, multistep process involving accumulation of genetic aberrations and alterations in gene expression patterns leading to uncontrolled cell division, invasion into surrounding tissue and finally dissemination and metastasis. We have previously shown that the Arg/Abl2 non receptor tyrosine kinase acts downstream of the EGF receptor and Src tyrosine kinases to promote invadopodium function in breast cancer cells, thereby promoting their invasiveness. However, whether and how Arg contributes to tumor development and dissemination in vivo has never been investigated. Using a mouse xenograft model, we show that knocking down Arg in breast cancer cells leads to increased tumor cell proliferation and significantly enlarged tumor size. Despite having larger tumors, the Arg-knockdown (Arg KD) tumor-bearing mice exhibit significant reductions in tumor cell invasion, intravasation into blood vessels and spontaneous metastasis to lungs. Interestingly, we found that proliferation associated genes in the Ras-MAPK (mitogen-activated protein kinase) pathway are upregulated in Arg KD breast cancer cells, as is Ras-MAPK signaling, while invasion-associated genes are significantly downregulated. These data suggest that Arg promotes tumor cell invasion and dissemination, while simultaneously inhibiting tumor growth. We propose that Arg acts as a switch in metastatic cancer cells that governs the decision to 'grow or go' (divide or invade). PMID- 22777353 TI - Histone arginine methylation keeps RUNX1 target genes in an intermediate state. AB - The coordinated recruitment of epigenetic regulators of gene expression by transcription factors such as RUNX1 (AML1, acute myeloid leukemia 1) is crucial for hematopoietic differentiation. Here, we identify protein arginine methyltransferase 6 (PRMT6) as a central functional component of a RUNX1 corepressor complex containing Sin3a and HDAC1 in human hematopoietic progenitor cells. PRMT6 is recruited by RUNX1 and mediates asymmetric histone H3 arginine-2 dimethylation (H3R2me2a) at megakaryocytic genes in progenitor cells. H3R2me2a keeps RUNX1 target genes in an intermediate state with concomitant H3K27me3 and H3K4me2 but not H3K4me3. Upon megakaryocytic differentiation PRMT6 binding is lost, the H3R2me2a mark decreases and a coactivator complex containing WDR5/MLL and p300/pCAF is recruited. This leads to an increase of H3K4me3 and H3K9ac, which result in augmented gene expression. Our results provide novel mechanistic insight into how RUNX1 activity in hematopoietic progenitor cells maintains differentiation genes in a suppressed state but poised for rapid transcriptional activation. PMID- 22777354 TI - Regulation of DCIS to invasive breast cancer progression by Singleminded-2s (SIM2s). AB - Singleminded-2s (SIM2s) is a member of the bHLH/PAS family of transcription factors and a key regulator of mammary epithelial cell differentiation. SIM2s is highly expressed in mammary epithelial cells and downregulated in human breast cancer. Loss of Sim2s causes aberrant mouse mammary ductal development, with features suggestive of malignant transformation, whereas overexpression of SIM2s promotes precocious alveolar differentiation in nulliparous mouse mammary glands, suggesting that SIM2s is required for establishing and enhancing mammary gland differentiation. To test the hypothesis that SIM2s regulates tumor cell differentiation, we analyzed SIM2s expression in human primary breast ductal carcinoma in situ (DCIS) samples and found that SIM2s is lost with progression from DCIS to invasive ductal cancer (IDC). Using a MCF10DCIS.COM progression model, we have shown that SIM2s expression is decreased in MCF10DCIS.COM cells compared with MCF10A cells, and reestablishment of SIM2s in MCF10DCIS.COM cells significantly inhibits growth and invasion both in vitro and in vivo. Analysis of SIM2s-MCF10DCIS.com tumors showed that SIM2s promoted a more differentiated tumor phenotype including the expression of a broad range of luminal markers (CSN2 (beta-casein), CDH1 (E-cadherin), and KER18 (keratin-18)) and suppressed genes associated with stem cell maintenance and a basal phenotype (SMO (smoothened), p63, SLUG (snail-2), KER14 (keratin-14) and VIM (vimentin)). Furthermore, loss of SIM2s expression in MCF10DCIS.COM xenografts resulted in a more invasive phenotype and increased lung metastasis likely due to an increase in Hedgehog signaling and matrix metalloproteinase expression. Together, these exciting new data support a role for SIM2s in promoting human breast tumor differentiation and maintaining epithelial integrity. PMID- 22777355 TI - Rictor regulates cell migration by suppressing RhoGDI2. AB - Rictor and its binding partner Sin1 are indispensable components of mTORC2 (mammalian target of rapamycin complex 2). The mTORC2 signaling complex functions as the regulatory kinase of the distinct members of AGC kinase family known to regulate cell proliferation and survival. In the early chemotaxis studies in Dictyostelium, the rictor's ortholog has been identified as a regulator of cell migration. How rictor regulates cell migration is poorly characterized. Here we show that rictor regulates cell migration by controlling a potent inhibitor of Rho proteins known as the Rho-GDP dissociation inhibitor 2 (RhoGDI2). On the basis of on our proteomics study we identified that the rictor-dependent deficiency in cell migration is caused by upregulation of RhoGDI2 leading to a low activity of Rac and Cdc42. We found that a suppression of RhoGDI2 by rictor is not related to the Sin1 or raptor function that excludes a role of mTORC2 or mTORC1 in regulation of RhoGDI2. Our study reveals that rictor by suppressing RhoGDI2 promotes activity of the Rho proteins and cell migration. PMID- 22777356 TI - Diminished functional role and altered localization of SHP2 in non-small cell lung cancer cells with EGFR-activating mutations. AB - Non-small cell lung cancer (NSCLC) cells harboring activating mutations of the epidermal growth factor receptor (EGFR) tend to display elevated activity of several survival signaling pathways. Surprisingly, these mutations also correlate with reduced phosphorylation of ERK and SHP2, a protein tyrosine phosphatase required for complete ERK activation downstream of most receptor tyrosine kinases. As ERK activity influences cellular response to EGFR inhibition, altered SHP2 function could have a role in the striking response to gefitinib witnessed with EGFR mutation. Here, we demonstrate that impaired SHP2 phosphorylation correlates with diminished SHP2 function in NSCLC cells expressing mutant, versus wild-type, EGFR. In NSCLC cells expressing wild-type EGFR, SHP2 knockdown decreased ERK phosphorylation, basally and in response to gefitinib, and increased cellular sensitivity to gefitinib. In cells expressing EGFR mutants, these effects of SHP2 knockdown were less substantial, but the expression of constitutively active SHP2 reduced cellular sensitivity to gefitinib. In cells expressing EGFR mutants, which do not undergo efficient ligand-mediated endocytosis, SHP2 was basally associated with GRB2-associated binder 1 (GAB1) and EGFR, and SHP2's presence in membrane fractions was dependent on EGFR activity. Whereas EGF promoted a more uniform intracellular distribution of initially centrally localized SHP2 in cells expressing wild-type EGFR, SHP2 was basally evenly distributed and did not redistribute in response to EGF in cells with EGFR mutation. Thus, EGFR mutation may promote association of a fraction of SHP2 at the plasma membrane with adapters that promote SHP2 activity. Consistent with this, SHP2 immunoprecipitated from cells with EGFR mutation was active, and EGF treatment did not change this activity. Overall, our data suggest that a fraction of SHP2 is sequestered at the plasma membrane in cells with EGFR mutation in a way that impedes SHP2's ability to promote ERK activity and identify SHP2 as a potential target for co-inhibition with EGFR in NSCLC. PMID- 22777358 TI - Downregulation of splicing factor SRSF3 induces p53beta, an alternatively spliced isoform of p53 that promotes cellular senescence. AB - Most human pre-mRNA transcripts are alternatively spliced, but the significance and fine-tuning of alternative splicing in different biological processes is only starting to be understood. SRSF3 (SRp20) is a member of a highly conserved family of splicing factors that have critical roles in key biological processes, including tumor progression. Here, we show that SRSF3 regulates cellular senescence, a p53-mediated process to suppress tumorigenesis, through TP53 alternative splicing. Downregulation of SRSF3 was observed in normal human fibroblasts undergoing replicative senescence, and was associated with the upregulation of p53beta, an alternatively spliced isoform of p53 that promotes p53-mediated senescence. Knockdown of SRSF3 by short interfering RNA (siRNA) in early-passage fibroblasts induced senescence, which was associated with elevated expression of p53beta at mRNA and protein levels. Knockdown of p53 partially rescued SRSF3-knockdown-induced senescence, suggesting that SRSF3 acts on p53 mediated cellular senescence. RNA pulldown assays demonstrated that SRSF3 binds to an alternatively spliced exon uniquely included in p53beta mRNA through the consensus SRSF3-binding sequences. RNA crosslinking and immunoprecipitation assays (CLIP) also showed that SRSF3 in vivo binds to endogenous p53 pre-mRNA at the region containing the p53beta-unique exon. Splicing assays using a transfected TP53 minigene in combination with siRNA knockdown of SRSF3 showed that SRSF3 functions to inhibit the inclusion of the p53beta-unique exon in splicing of p53 pre-mRNA. These data suggest that downregulation of SRSF3 represents an endogenous mechanism for cellular senescence that directly regulates the TP53 alternative splicing to generate p53beta. This study uncovers the role for general splicing machinery in tumorigenesis, and suggests that SRSF3 is a direct regulator of p53. PMID- 22777359 TI - Cancer-associated lysosomal changes: friends or foes? AB - Rapidly dividing and invasive cancer cells are strongly dependent on effective lysosomal function. Accordingly, transformation and cancer progression are characterized by dramatic changes in lysosomal volume, composition and cellular distribution. Depending on one's point of view, the cancer-associated changes in the lysosomal compartment can be regarded as friends or foes. Most of them are clearly transforming as they promote invasive growth, angiogenesis and drug resistance. The same changes can, however, strongly sensitize cells to lysosomal membrane permeabilization and thereby to lysosome-targeting anti-cancer drugs. In this review we compile our current knowledge on cancer-associated changes in lysosomal composition and discuss the consequences of these alterations to cancer progression and the possibilities they can bring to cancer therapy. PMID- 22777357 TI - Terminal differentiation and loss of tumorigenicity of human cancers via pluripotency-based reprogramming. AB - Pluripotent cells can be derived from various types of somatic cells by nuclear reprogramming using defined transcription factors. It is, however, unclear whether human cancer cells can be similarly reprogrammed and subsequently terminally differentiated with abrogation of tumorigenicity. Here, using sarcomas we show that human-derived complex karyotype solid tumors: (1) can be reprogrammed into a pluripotent-like state as defined by all in vitro criteria used to define pluripotent stem cells generated from somatic cells; (2) can be terminally differentiated into mature connective tissue and red blood cells; and (3) terminal differentiation is accompanied with loss of both proliferation and tumorigenicity. We go on to perform the first global DNA promoter methylation and gene expression analyses comparing human cancers to their reprogrammed counterparts and report that reprogramming/differentiation results in significant epigenetic remodeling of oncogenes and tumor suppressors, while not significantly altering the differentiation status of the reprogrammed cancer cells, in essence dedifferentiating them to a state slightly before the mesenchymal stem cell differentiation stage. Our data demonstrate that direct nuclear reprogramming can restore terminal differentiation potential to human-derived cancer cells, with simultaneous loss of tumorigenicity, without the need to revert to an embryonic state. We anticipate that our models would serve as a starting point to more fully assess how nuclear reprogramming overcomes the multitude of genetic and epigenetic aberrancies inherent in human cancers to restore normal terminal differentiation pathways. Finally, these findings suggest that nuclear reprogramming may be a broadly applicable therapeutic strategy for the treatment of cancer. PMID- 22777360 TI - RelB inhibits cell proliferation and tumor growth through p53 transcriptional activation. AB - The alternative nuclear factor-kappaB (NF-kappaB) -activation pathway proceeds via inducible p100 processing, leading to the activation of RelB-containing dimers. This pathway is aberrantly activated in several types of tumors; however, a direct role for RelB in the control of cell proliferation is still largely unexplored. Here, we demonstrate that RelB provides cell proliferation-inhibitory signals in murine fibroblasts. In agreement with these results, RelB ectopic expression inhibits xenograft tumor growth in vivo, whereas RelB knockdown enhances it. Significantly, we show that RelB inhibits cell proliferation and tumor growth in a p53-dependent manner. Mechanistic studies indicate that RelB regulates the transcription of the p53 tumor-suppressor gene through direct recruitment to the p53 promoter, thus increasing both p53 protein levels and expression of p53 target genes such as p21. Our findings define a novel link between NF-kappaB and growth-inhibitory pathways involving the RelB-dependent transcriptional upregulation of p53. Furthermore, they suggest that inhibition of RelB in some tumor types that retain wild-type p53 may diminish rather than improve therapeutic responses. PMID- 22777361 TI - Characteristics of fertile somatic hybrids of G. hirsutum L. and G. trilobum generated via protoplast fusion. AB - Fertile somatic hybrids between tetraploid upland cotton G. hirsutum L. cv. Coker 312 and wild cotton G. trilobum were generated by symmetric electrofusion. Comparisons of morphology, combined with flow cytometric, RAPD, SRAP and AFLP analyses confirmed the hybrid nature of the regenerated plants. The hybrids differed morphologically from the parent plants. Flow cytometric analysis showed that the hybrids had DNA similar in amount to the total combined DNA content of the two parents, and the use of molecular markers revealed that the hybrids contained genomic fragments from both fusion parents, further indicating the hybrid nature of the regenerated plants. The stability of the morphological features of the hybrids was examined in following generations. The hexaploid fusion plants showed strong photosynthesis and a high expression level of some photosystem-related genes. Our results suggest that novel traits may be incorporated in cotton breeding programs through the production of somatic hybrids and the backcrossing of these plants with elite cultivars. PMID- 22777362 TI - Painful eccrine spiradenoma containing nerve fibers: a case report. AB - An eccrine spiradenoma is a rare benign tumor most often seen in the head, neck and upper trunk of young adults. Although spontaneous pain or tenderness is a typical symptom of eccrine spiradenomas, the underlying mechanism has not been fully elucidated. Here, we report the case of a 47- year-old woman who had a spiradenoma in the subcutaneous tissue of her posterior neck accompanied by agonizing pain which was triggered by pressure. Multiple nodular lesions were excised and the typical histopathological findings of spiradenoma were seen. The histopathological architecture of a disorganized nerve fiber encasing the tumor nodules appeared to correlate with the unique clinical symptom of pain. PMID- 22777363 TI - Differences in self-assessed health by socioeconomic group amongst people with and without a history of cancer: an analysis using representative data from Scotland. AB - INTRODUCTION: This paper considers socioeconomic inequalities in self-assessed health amongst people with and without a history of cancer using representative data from Scotland. METHODS: A cross-sectional analysis using the Scottish Health Survey was done. Cancer survivors were identified using linked Cancer Registry data. Bivariate and multivariate analysis was used to compare and contrast self assessed health amongst those with a history of cancer to those without. RESULTS: Of the 17,505 survey participants, 432 (2.5 %) had a history of cancer. After taking into account potential confounders, those in the lowest socioeconomic group were more likely to report poor health than those in the highest group amongst those with a history of cancer [odds ratio, 2.96; confidence interval (CI), 1.82-4.80] and those with no history of cancer (odds ratio, 2.45; CI, 2.21 2.71). Those in the lowest socioeconomic group with no history of cancer had a greater propensity to report poor health than any of the highest groups that did have a history of cancer (p < 0.01). Differences in propensities to indicate poor health were particularly marked amongst those 4 years or more post-cancer diagnosis. CONCLUSIONS: Findings underline the scale of socioeconomic gradients in health. That disparities were so wide amongst those most temporally distant from initial diagnosis is particularly a concern given improving survival after a cancer diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Socioeconomic circumstances have a considerable influence on health and well-being. Practitioners and policy makers should consider socioeconomic circumstances in considering approaches to health and social care of cancer survivors. PMID- 22777364 TI - Models of care for post-treatment follow-up of adult cancer survivors: a systematic review and quality appraisal of the evidence. AB - PURPOSE: The impact of cancer and cancer treatment on the long-term health and quality of life of survivors is substantial, leading to questions about the most appropriate configuration of services and models of care for follow-up of post primary treatment survivors. METHODS: A systematic review and quality appraisal of the health literature for structure of services and models of follow-up care for post-treatment survivors was identified through a search of guideline sources and empirical databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Library, CINAHL, and EBSCO from 1999 through December 2009. RESULTS: Ten practice guidelines and nine randomized controlled trials comprised the evidence base for models of care for adult cancer survivors. Although the evidence base was rated as low quality, nurse-led and primary care physician models of follow-up care were equivalent for detecting recurrence. Consensus also suggests that cancer survivors may benefit from coordinated transition planning that includes the provision of survivorship care plans as part of standard care. CONCLUSIONS: Realignment of models of care is identified as a health system priority to meet the supportive care and surveillance needs of a burgeoning survivor population. Further research is needed to evaluate the efficacy of models of care in a broader population of cancer survivors with differing needs and risks. While the evidence is limited, there is research that may be used to guide the configuration of health care services and planning. PMID- 22777365 TI - FPMRS Indexed. PMID- 22777366 TI - Guidelines for providing privileges and credentials to physicians for transvaginal placement of surgical mesh for pelvic organ prolapse. AB - The adoption of new technology or procedures into a clinician's surgical armamentarium is driven by multiple factors. Patient safety and anticipated long term improvement in outcomes should be the primary objective that guides a surgeon's decision to deliver care involving new procedures. Surgically complex procedures require a balance of knowledge, surgical skill, and experience, with appropriate ongoing surgical volume and monitoring of outcomes and adverse events. Transvaginal placement of surgical mesh for pelvic organ prolapse has the potential to improve quality of life and anatomic outcomes (especially in the anterior compartment), but also has potential serious adverse events as outlined by the FDA's July 2011 Safety Communication. This document provides Guidelines for privileging and credentialing of physicians planning to implement or continue using this new technology in clinical practice. PMID- 22777367 TI - Validation of the surgical pain scales in women undergoing pelvic reconstructive surgery. AB - OBJECTIVE: Surgical pain scales (SPS) consist of 4 items that measure pain at rest, during normal activities, and during work/exercise and quantify unpleasantness of worst pain, which are valid and responsive in men undergoing hernia repair. Our objective was to evaluate the psychometric properties of SPS in women undergoing vaginal surgery for pelvic organ prolapse and stress urinary incontinence. METHODS: We modified SPS by converting original response scales from a visual analog scale to numerical rating scales. Numerical rating scales have lower error rates and higher validity than visual analog scale. The sample included 169 women with stage II to IV pelvic organ prolapse and stress urinary incontinence in a randomized trial comparing sacrospinous ligament fixation to uterosacral vault suspension with and without pelvic floor muscle training. Participants completed SPS and SF-36 at baseline, and 2 weeks and 6 months after surgery. Construct validity and responsiveness were examined in cross-sectional and longitudinal data using Pearson correlation and analysis of variance. RESULTS: Pain at rest, during normal activities, and during work/exercise worsened at 2 weeks (P<0.05); and all measures of pain improved from baseline to 6 months (P<0.0001). Construct validity was demonstrated by correlations of 0.51 to 0.74 between SPS and the SF-36 Bodily Pain Scale (P<0.0001). Pain worsened on SF-36 between baseline and 2 weeks in 63% of the participants, and this group demonstrated a mean (SD) increase in pain of 1.9 (2.8) on the SPS (effect size, 0.99), confirming responsiveness of the scale. CONCLUSIONS: The modified SPS are valid and responsive in women after pelvic reconstructive surgery. PMID- 22777368 TI - Validation of the activities assessment scale in women undergoing pelvic reconstructive surgery. AB - OBJECTIVE: The Activities Assessment Scale (AAS) is a 13-item postoperative functional activity scale validated in men who underwent hernia surgery. We evaluated the psychometric characteristics of the AAS in women who underwent vaginal surgery for pelvic organ prolapse (POP) and stress urinary incontinence (SUI). METHODS: Participants included 163 women with POP and SUI enrolled in a randomized trial comparing sacrospinous ligament fixation to uterosacral vault suspension with and without perioperative pelvic floor muscle training. Participants completed the AAS and SF-36 at baseline and 2 weeks and 6 months postoperatively. Internal reliability of the AAS was evaluated using Cronbach alpha. Construct validity and responsiveness were examined in cross-sectional and longitudinal data using Pearson correlation coefficient and analysis of variance. The AAS is scored from zero to 100 (higher scores=better function). RESULTS: Mean (SD) baseline AAS score was 87 (17.3) (range, 25-100). Functional activity declined from baseline to 2 weeks postoperatively (mean change, -4.5; 95% confidence interval, -7.6 to -1.42) but improved above baseline at 6 months (mean change, +10.9; 95% confidence interval, 7.8-14.0). Internal reliability of the AAS was excellent (Cronbach alpha=0.93). Construct validity was demonstrated by a correlation of 0.59 to 0.60 between the AAS and SF-36 physical functioning scale (P<0.0001) and lower correlations between the AAS and other SF-36 scales. Patients who improved in physical functioning based on the SF-36 between 2 weeks and 6 months postoperatively showed an effect size of 0.86 for change in the AAS over the same period. CONCLUSIONS: The AAS is a valid, reliable, and responsive measure for evaluation of physical function in women after pelvic reconstructive surgery. PMID- 22777370 TI - Midurethral sling for treatment of occult stress urinary incontinence at the time of colpocleisis: a decision analysis. AB - OBJECTIVE: The objective of this study was to estimate optimal timing for treatment of occult stress urinary incontinence in women undergoing colpocleisis using decision analysis methodology. METHODS: A decision tree was constructed comparing concomitant versus staged midurethral slings (MUSs). Simple roll-back methodology was used to determine average 1-year utilities of the compared approaches. RESULTS: One-year overall utility favored the staged approach to treating occult incontinence (0.945 vs 0.908) at time of colpocleisis. However, this difference was less than the accepted minimally important difference for utilities. Multiple 1-way sensitivity analyses of all utilities and probabilities identified few thresholds, confirming model robustness. In our model, only 22.5% of women in the staged group ultimately underwent MUS. CONCLUSIONS: Staged and concomitant MUSs have similar overall utilities. Both strategies are clinically reasonable, and surgical decision making should be tailored to individual patient needs and preferences. In our model, a staged approach greatly reduces the number of MUS performed. PMID- 22777369 TI - A randomized clinical trial of the impact of local estrogen on postoperative tissue quality after vaginal reconstructive surgery. AB - OBJECTIVE: To evaluate the use and effect of early administration of vaginal estrogen via a continuous low-dose estradiol vaginal ring placed immediately after pelvic reconstructive surgery. METHODS: This was a randomized controlled trial of 65 postmenopausal women undergoing vaginal reconstructive surgery. The subjects were randomly assigned to receive an estradiol-releasing vaginal ring, placebo vaginal ring, or control without vaginal ring for 12 weeks immediately after vaginal reconstructive surgery. The primary outcome was tissue quality based on vaginal maturation 3 months postoperatively. Secondary outcome measures were subjective and objective signs of atrophy; vaginal pH; the presence of granulation tissue, microscopic inflammation, and major healing abnormalities; and the ability to tolerate an intravaginal ring. RESULTS: At 12 weeks, the estradiol ring group had a significantly improved maturation value (P<0.01) and objective atrophy assessment (P<0.01) compared with the placebo ring and control arms. Granulation tissue was increased in the placebo ring arm (P<0.01). Subjective atrophy scores did not differ among the groups (P=0.39). CONCLUSIONS: Early administration of vaginal estrogen after vaginal surgery via an estradiol releasing ring is feasible and results in improved markers of tissue quality postoperatively compared to placebo and controls. PMID- 22777371 TI - Psychometric evaluation of health-related quality-of-life measures after pelvic organ prolapse surgery. AB - OBJECTIVE: To evaluate the psychometric characteristics of the Pelvic Floor Distress Inventory (PFDI-20), the Pelvic Floor Impact Questionnaire (PFIQ-7), and the Patient Global Impression of Change (PGIC) among women undergoing pelvic organ prolapse (POP) repair surgery. METHODS: Data were collected at baseline and 12 months from 2 single-arm trials of surgical repair of POP using mesh. At each time point, internal consistency reliability (Cronbach's alpha) was calculated for the PFDI-20 and PFIQ-7 total scores and for each subscale. Concurrent validity was assessed with baseline and follow-up data using Spearman's rank order correlation coefficients. Responsiveness was assessed by calculating change scores from baseline to each follow-up visit, effect sizes, standard error of measurement (SEM), and using PFDI-20 and PFIQ-7 change scores stratified by PGIC. RESULTS: The women (N=275: study 1, n=148; study 2, n=127) had a mean (SD) of 64.4 (10.3) years of age. At baseline, the women had a mean (SD) stage II (n=83), stage III (n=173), or stage IV (n=19) POP quantification. At baseline, the internal consistency reliability of the PFDI-20 full and subscales ranged from 0.64 to 0.85, and that of the PFIQ-7 ranged from 0.89 to 0.96. Concurrent validity was good for the PFDI-20 and PFIQ-7 (r range, 0.35-0.59). The PFDI-20, the PFIQ-7, and the PGIC were responsive. CONCLUSION: The PFDI-20, the PFIQ-7, and the PGIC are psychometrically sound measures of patients' perceptions of change after POP surgery and will be useful for those interested in evaluating perceptions of patients undergoing surgical POP repair. PMID- 22777372 TI - Longitudinal changes in pelvic organ support among parous women. AB - OBJECTIVE: The objective of this study was to characterize changes in pelvic organ support and symptoms of prolapse over time and identify characteristics associated with worsening of support. METHODS: Participants were recruited based on the mode of delivery (cesarean vs vaginal delivery) of their first child. The Pelvic Organ Prolapse Quantification system was used to describe support at baseline and 12 to 18 months later. Symptoms were assessed using a validated questionnaire. Outcomes of interest included the proportion of women with a change in support greater than 1 cm at the anterior vaginal wall (Ba) or posterior vaginal wall (Bp) and a change in support greater than 2 cm at the apex (C). Characteristics associated with worsening of support were identified using 2 sided Fisher's exact test and multivariable logistic regression. RESULTS: Among 749 participants, 60% had delivered by cesarean delivery only. Worsening support at Ba, Bp, and C was observed in 8%, 2%, and 6%, respectively. Worsening at any point was observed in 110 women (15%). Women with prolapse symptoms at baseline were not more likely to experience worsening of support. In a multivariable model, age older than 40 years (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.09-2.49), vaginal delivery (OR, 3.12; 95% CI, 1.38-7.07), and genital hiatus greater than or equal to 2 (OR, 2.36; 95% CI, 1.03-5.43) were all associated with worsening support in at least 1 compartment. CONCLUSIONS: Over 12 to 18 months, characteristics most strongly associated with worsening of pelvic support include genital hiatus size, vaginal birth, and age. PMID- 22777373 TI - TVT-Secur in office sling procedure under local anesthesia: a prospective 2-year analysis. AB - OBJECTIVE: Our objective was to assess long-term safety, feasibility, and success of performing single-incision mini-sling tension-free vaginal tape (TVT)-Secur (TVT-S) procedure in the office under local anesthesia for stress urinary incontinence. METHOD: Fifty subjects were enrolled from October 2008 to May 2009. The TVT-S procedure (Hammock approach) was performed per strict guidelines. Success was based on a composite score of 7 subjective and objective measures at 24 months. RESULTS: Success per the composite score was 80%. Retreatment for stress urinary incontinence was 9%. There was significant improvement in quality of life and symptom relief scores (P<0.001). Ninety-four percent were satisfied with the surgical outcome, and 98% felt they made the right decision. There were no intraoperative injuries or complications. Two subjects had mesh exposure in the vagina. CONCLUSION: In-office single-incision mini-sling TVT-S is safe, feasible, and successful with minimal complications; however, strict criteria need to be followed. PMID- 22777374 TI - Sexual function after vaginal versus nonvaginal prolapse surgery. AB - OBJECTIVES: To compare sexual function based on the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ) in women who underwent vaginal versus nonvaginal surgery for prolapse. METHODS: This was a prospective cohort study of women who underwent vaginal versus nonvaginal (abdominal or robotic) surgery for stage II to stage IV pelvic organ prolapse. We compared 2 groups: those who received vaginal prolapse surgery (defined as any surgical procedure for prolapse requiring incisions in the vaginal wall) and those who received nonvaginal (ie, exclusively abdominal or robotic) prolapse surgery. Women completed the PISQ and additional pelvic floor symptom questionnaires at baseline and 6 months after surgery. Our primary outcome was change in PISQ score from baseline to 6 months. RESULTS: Of the 80 women in our study population, 58 participants completed 6-month follow-up. Baseline PISQ and pelvic floor symptom questionnaire scores were similar between the vaginal and nonvaginal surgery groups. There were significant overall improvements in sexual function based on the PISQ but no differences in scores between vaginal and nonvaginal surgery groups (mean PISQ change score 6.4+/-9.2 vs 6.1+/-14.8; P=0.92). In a linear regression model adjusting for potential confounders, there were still no differences in 6-month PISQ scores between the groups. CONCLUSIONS: In women with prolapse, sexual function is likely to improve after reconstructive surgery, regardless of the route. PMID- 22777375 TI - Does obesity impact the success of an InterStim test phase for the treatment of refractory urge urinary incontinence in female patients? AB - OBJECTIVES: Some providers believe obesity may be a relative contraindication for InterStim; however, the relationship between obesity and treatment outcome has not been evaluated. Our objectives were to compare the test phase (stage 1) success and complications of obese versus nonobese women undergoing a 2-stage InterStim procedure for refractory urge urinary incontinence (UUI). METHODS: We conducted a retrospective cohort study of obese and nonobese women who underwent stage 1 InterStim for refractory UUI. We compared the stage 1 success, defined as undergoing stage 2 generator implantation after demonstrating improvement of 50% or greater during test phase and intraoperative and postoperative complications within 1 year between obese and nonobese cohorts. RESULTS: Of 149 subjects, 80 (53.7%) were obese (body mass index, 37.3+/-5.87 kg/mg), and 69 (46.3%) were nonobese (body mass index, 25.6+/-2.82 kg/m). The overall stage 1 success was 81%. No statistically significant difference existed in stage 1 success between obese and nonobese cohorts (83% vs 78%, P=0.52). In a logistic regression model controlling for obesity, age, preoperative incontinence episodes per 24 hours, psychiatric diagnoses, arthritis, and diabetes mellitus, age per decade was the only variable significantly associated with stage 1 InterStim success (odds ratio, 0.61; 95% confidence interval, 0.39-0.96). Complications were also similar between cohorts (obese 20% vs nonobese 13%, P=0.26). CONCLUSIONS: In women undergoing staged InterStim therapy, stage 1 success and complications were similar between obese versus nonobese women. These data suggest that obesity should not be considered a limiting factor when determining whether a patient is a candidate for InterStim therapy for treatment of refractory UUI. PMID- 22777376 TI - Case report: a novel method for uterine-sparing hysteropexy. AB - OBJECTIVE: The objective of this study was to describe a technique for uterine sparing hysteropexy. CASE REPORT: A 50-year-old multiparous woman with pelvic organ prolapse underwent laparoscopic sacrohysteropexy utilizing polypropylene mesh with good clinical result. CONCLUSIONS: Placement of mesh arms medial to the uterine vessels during a laparoscopic sacrohysteropexy can be facilitated by using blunt needles to introduce the mesh arms. PMID- 22777377 TI - Inflammatory myofibroblastic tumor of the urinary tract following a TVT. AB - The complications related to the retropubic placement of polypropylene mesh (TVT) for stress urinary incontinence have been extensively described in the literature. The occurrence of an inflammatory myofibroblastic tumor, however, has not been previously reported as a complication of placement of a mesh sling. We report such a case in a patient with neurofibromatosis who had undergone a TVT for stress urinary incontinence and present a brief review of the literature. PMID- 22777378 TI - Plasma cell mucositis of the vagina: a case report. AB - BACKGROUND: Plasma cell mucositis is a rare dermatologic condition known to affect the upper aerodigestive tract and external genitalia but has never yet been described to affect the vaginal epithelium. CASE: A 57-year-old woman presented to the urogynecology clinic with chief complaint of symptomatic pelvic organ prolapse and vaginal spotting. Examination of the pelvis revealed grade 2 pelvic organ prolapse and diffuse multifocal erythematous patches on the vaginal introitus, vagina, cervix, and periurethra. Histopathologic examination of biopsies revealed plasma cell mucositis. CONCLUSION: This is the first report of plasma cell mucositis affecting vaginal epithelium. It is possible that pelvic organ prolapse caused irritation and inflammation of vaginal epithelium and contributed to the development of plasma cell mucositis in these areas. PMID- 22777379 TI - The role of antiangiogenic agents in the treatment of head and neck cancer. AB - Despite progress in the treatment of locally advanced head and neck squamous cell cancer (HNSCC), the prognosis remains dismal and 5-year survival does not exceed 40%. In metastatic and recurrent disease, in spite of the introduction of cetuximab in combination with platinum and fluorouracil, the median overall survival rate remains lower than 11 months. There are many possible reasons for these disappointing results including acquired drug resistance and tumor hypoxia. Angiogenesis plays an important role in HNSCC development and proliferation. Promising preclinical results with antiangiogenic therapies have engendered a number of clinical trials, but so far there have not been any conclusive results on the value of such treatments. This paper aims to review the role of angiogenesis in head and neck cancer and to suggest future perspectives. PMID- 22777380 TI - Factors important to patients' quality of life at the end of life. AB - BACKGROUND: When curative treatments are no longer options for patients dying of cancer, the focus of care often turns from prolonging life to promoting quality of life (QOL). Few data exist on what predicts better QOL at the end of life (EOL) for advanced cancer patients. The purpose of this study was to determine the factors that most influence QOL at the EOL, thereby identifying promising targets for interventions to promote QOL at the EOL. METHODS: Coping With Cancer is a US multisite, prospective, longitudinal cohort study of 396 advanced cancer patients and their informal caregivers who were enrolled from September 1, 2002, through February 28, 2008. Patients were followed up from enrollment to death a median of 4.1 months later. Patient QOL in the last week of life was a primary outcome of Coping With Cancer and the present report. RESULTS: The following set of 9 factors, preceded by a sign indicating the direction of the effect and presented in rank order of importance, explained the most variance in patients' QOL at the EOL: 1 = (-) intensive care unit stays in the final week (explained 4.4% of the variance in QOL at the EOL), 2 = (-) hospital deaths (2.7%), 3 = (-) patient worry at baseline (2.7%), 4 = (+) religious prayer or meditation at baseline (2.5%), 5 = site of cancer care (1.8%), 6 = (-) feeding-tube use in the final week (1.1%), 7 = (+) pastoral care within the hospital or clinic (1.0%), 8 = (-) chemotherapy in the final week (0.8%), and 9 = (+) patient-physician therapeutic alliance at baseline (0.7%). The vast majority of the variance in QOL at the EOL, however, remained unexplained. CONCLUSION: Advanced cancer patients who avoid hospitalizations and the intensive care unit, who are less worried, who pray or meditate, who are visited by a pastor in the hospital/clinic, and who feel a therapeutic alliance with their physicians have the highest QOL at the EOL. PMID- 22777381 TI - Penetrating brain injury caused by retained plastic tip of ballpoint pen. PMID- 22777382 TI - A retrospective study of posterior malleolus fractures. AB - PURPOSE: In this retrospective study, we evaluated the treatment effect of ankle joint fracture surgery involving the posterior malleolus, and discuss relevant factors influencing the occurrence of traumatic arthritis of the ankle joint. METHODS: A total of 102 cases of ankle joint fractures involving the posterior malleolus in five large-scale skeletal trauma centres in China, from January 2000 to July 2009, were retrospectively analysed in terms of surgical treatment and complete follow-up. Ankle joint mobility, posterior malleolus fragment size, articular surface evenness, Ankle-Hindfoot Scale of the American Orthopedic Foot and Ankle Society (AOFAS) score, and imaging scale score for arthritis were recorded. The degree of fracture pain during rest, active movement, and weight bearing walking, and satisfaction with treatment were evaluated using a visual analogue scale (VAS). RESULTS: The average AOFAS score was 95.9, excellence rate was 92.2 %, and average VAS scores for degree of fracture pain during rest, active movement, and weight-bearing walking were 0.15, 0.31, and 0.68, respectively. Thirty-six cases showed arthritic manifestations. Ankle joint mobility along all directions on the injured side was lower than that on the unaffected side. There was no obvious difference in treatment effect between the fixed and unfixed posterior malleolus fragment groups for all and for fragment size of < 25 %; between fixing the posterior malleolus fragment from front to back or from back to front; or between elderly patients (>= 60 years old) and young patients (< 60 years old). There was a distinct difference in the treatment effect between articular surface evenness and unevenness for all and for fragment size of >= 25 %. CONCLUSIONS: For all 102 cases of ankle joint fracture involving the posterior malleolus, the treatment effect was satisfactory. Restoration of an even articular surface, especially when fragment size >= 25 %, should be attempted during treatment. PMID- 22777383 TI - Long-term stress distribution patterns of the ankle joint in varus knee alignment assessed by computed tomography osteoabsorptiometry. AB - PURPOSE: The stress distribution of an ankle under various physiological conditions is important for long-term survival of total ankle arthroplasty. The aim of this study was to measure subchondral bone density across the distal tibial joint surface in patients with malalignment/instability of the lower limb. METHODS: We evaluated subchondral bone density across the distal tibial joint in patients with malalignment/instability of the knee by computed tomography (CT) osteoabsorptiometry from ten ankles as controls and from 27 ankles with varus deformity/instability of the knee. The quantitative analysis focused on the location of the high-density area at the articular surface, to determine the resultant long-term stress on the ankle joint. RESULTS: The area of maximum density of subchondral bone was located in the medial part in all subjects. The pattern of maximum density in the anterolateral area showed stepwise increases with the development of varus deformity/instability of the knee. CONCLUSIONS: Our results should prove helpful for designing new prostheses and determining clinical indications for total ankle arthroplasty. PMID- 22777384 TI - Long-term outcomes following single-bundle transtibial arthroscopic posterior cruciate ligament reconstruction. AB - PURPOSE: Posterior cruciate ligament (PCL) injury has a reported incidence of 3 20 %. PCL reconstruction is aimed at reducing onset of premature articular degeneration and improving function. Numerous operative techniques have been described with varying degrees of result consistency. METHODS: We evaluated 15 patients treated for isolated primary posterior cruciate ligament injury with a mean follow-up of 4.1 years (range one to nine). Post-reconstruction clinical assessment included the Lysholm and Tegner knee scoring scale, international knee documentation committee (IKDC) ligament evaluation, and KT2000 arthrometer assessment. RESULTS: On the Lysholm knee score 11 patients (73 %) had excellent results, three patients (20 %) had good results and one patient (7 %) had a poor result. On the Tegner activity score the majority of patients scored 7-8 with a return to high level sports. At the final follow-up, the post-reconstruction IKDC score was normal or nearly normal (A and B) in 14 (93 %) patients, and abnormal (C) in one (7 %) patient. According to KT-2000 arthrometer measurements at final follow-up review, 11 patients (73 %) were rated as normal (A, 0-2 mm), and four patients (27 %) as nearly normal (B, 3-5 mm). These results were independent of age, mechanism of injury, time elapsed to surgical reconstruction, and length of follow-up. CONCLUSIONS: Despite being a technically demanding procedure, the outcomes reported in this study show that single bundle transtibial arthroscopic PCL repair using four strands hamstring autograft provides satisfactory and consistent functional outcomes. PMID- 22777385 TI - Sensitivity to biases of case-control studies on medical procedures, particularly surgery and blood transfusion, and risk of Creutzfeldt-Jakob disease. AB - BACKGROUND: Evidence of risk of Creutzfeldt-Jakob disease (CJD) associated with medical procedures, including surgery and blood transfusion, is limited by susceptibility to bias in epidemiological studies. METHODS: Sensitivity to bias was explored using a central-birth-cohort model using data from 18 case-control studies obtained after a review of 494 reports on medical procedures and risk of CJD, systematic for the period January 1, 1989 to December 31, 2011. RESULTS: The validity of the findings in these studies may have been undermined by: recall; control selection; exposure assessment in life-time periods of different duration, out of time-at-risk of effect, or asymmetry in case/control data; and confounding by concomitant blood transfusion at the time of surgery. For sporadic CJD (sCJD), a history of surgery or blood transfusion was associated with risk in some, but not all, recent studies at a >=10 year lag time, when controls were longitudinally sampled. Space-time aggregation of surgical events was not seen. Surgery at early clinical onset might be overrepresented among cases. Neither surgical history nor blood transfusion unlabelled for donor status, dental treatments or endoscopic examinations were linked to variant CJD (vCJD). CONCLUSIONS: These results indicate the need for further research. Common challenges within these studies include access to and content of past medical/dental treatment records for diseases with long incubation periods. PMID- 22777386 TI - Resveratrol biosynthesis: plant metabolic engineering for nutritional improvement of food. AB - The plant polyphenol trans-resveratrol (3, 5, 4'-trihydroxystilbene) mainly found in grape, peanut and other few plants, displays a wide range of biological effects. Numerous in vitro studies have described various biological effects of resveratrol. In order to provide more information regarding absorption, metabolism, and bioavailability of resveratrol, various research approaches have been performed, including in vitro, ex vivo, and in vivo models. In recent years, the induction of resveratrol synthesis in plants which normally do not accumulate such polyphenol, has been successfully achieved by molecular engineering. In this context, the ectopic production of resveratrol has been reported to have positive effects both on plant resistance to biotic stress and the enhancement of the nutritional value of several widely consumed fruits and vegetables. The metabolic engineering of plants offers the opportunity to change the content of specific phytonutrients in plant - derived foods. This review focuses on the latest findings regarding on resveratrol bioproduction and its effects on the prevention of the major pathological conditions in man. PMID- 22777388 TI - p38 Mitogen-activated protein kinase/signal transducer and activator of transcription-3 pathway signaling regulates expression of inhibitory molecules in T cells activated by HIV-1-exposed dendritic cells. AB - Human immunodeficiency virus type 1 (HIV-1) infection enhances the expression of inhibitory molecules on T cells, leading to T-cell impairment. The signaling pathways underlying the regulation of inhibitory molecules and subsequent onset of T-cell impairment remain elusive. We showed that both autologous and allogeneic T cells exposed to HIV-pulsed dendritic cells (DCs) upregulated cytotoxic T-lymphocyte antigen (CTLA-4), tumor-necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), lymphocyte-activation gene-3 (LAG3), T-cell immunoglobulin mucin-3 (TIM-3), CD160 and certain suppression-associated transcription factors, such as B-lymphocyte induced maturation protein-1 (BLIMP 1), deltex homolog 1 protein (DTX1) and forkhead box P3 (FOXP3), leading to T cell suppression. This induction was regulated by p38 mitogen-activated protein kinase/signal transducer and activator of transcription-3 (P38MAPK/STAT3) pathways, because their blockade significantly abrogated expression of all the inhibitory molecules studied and a subsequent recovery in T-cell proliferation. Neither interleukin-6 (IL-6) nor IL-10 nor growth factors known to activate STAT3 signaling events were responsible for STAT3 activation. Involvement of the P38MAPK/STAT3 pathways was evident because these proteins had a higher level of phosphorylation in the HIV-1-primed cells. Furthermore, blockade of viral CD4 binding and fusion significantly reduced the negative effects DCs imposed on primed T cells. In conclusion, HIV-1 interaction with DCs modulated their functionality, causing them to trigger the activation of the P38MAPK/STAT3 pathway in T cells, which was responsible for the upregulation of inhibitory molecules. PMID- 22777389 TI - Potential role of high mobility group box protein 1 and intermittent PTH (1-34) in periodontal tissue repair following orthodontic tooth movement in rats. AB - OBJECTIVES: Recent studies indicate that high mobility group box protein 1 (HMGB1) can be released by necrotic and damaged cells and functions as an alarmin that is recognized by the innate immune system. Little is known about the role of HMGB1 within the periodontal ligament (PDL). Therefore, we examined HMGB1 expression by PDL cells in vitro and compared the findings to an in vivo model of orthodontically induced tooth root resorption. In addition, we addressed the question of whether a potentially anabolic intermittent administration of parathyroid hormone (iPTH) would modulate the expression of HMGB1. MATERIALS AND METHODS: In confluent PDL cell cultures, HMGB1 messenger RNA (mRNA) expression was quantified by real-time polymerase chain reaction. In a rat model comprising 25 animals, mechanical loading for 5 days was followed by administration of either iPTH (1-34) systemically or sham injections for up to 56 days. HMGB1 expression was determined by means of immunohistochemistry and histomorphometry. RESULTS: The in vitro experiments revealed an inhibitory effect of iPTH on basal HMGB1 mRNA expression in confluent PDL cells. In vivo, the mechanical force induced enhanced HMGB1 protein expression declined time dependently. Intermittent PTH further inhibited HMGB1 expression. The significantly higher basal HMGB1 protein expression in the former compression side was followed by a more pronounced time- and iPTH-dependent decline in the same area. CONCLUSIONS: These data indicate a major role for HMGB1 in the regulation of PDL wound healing following mechanical load-induced tissue injury. CLINICAL RELEVANCE: The findings point to the potential benefit of iPTH in the attempt to support these immune associated reparative processes. PMID- 22777390 TI - A micro-computed tomography study of the root canal morphology of the mandibular first premolar in a population from southwestern China. AB - OBJECTIVES: This study aimed to investigate the root canal morphology of mandibular first premolar teeth in a population from southwestern China by micro computed tomography (micro-CT). MATERIALS AND METHODS: Human mandibular first premolars (115) were selected and prepared for micro-CT analysis with a slice thickness of 30 MUm. Details of root canal orifices, canals, accessory canals, apical foramina-apical delta intercanal communication, loops and isthmuses, and mesial invagination were analyzed from reconstructed three-dimensional (3D) images. RESULTS: Canal patterns categorized according to the classification defined by Vertucci (Endod Top 10:3-29, 2005) as types I (65.2%), III (2.6%), V (22.6%), and VII were identified (0.9%). Accessory canals were present in 35.7% of the samples and were predominantly located in the apical third of the root. A single apical foramen was observed in 50.4% of the samples and two or three foramina in 28.7% and 14.8%, respectively. Apical delta was identified in 6.1% of the samples and the prevalence of intercanal communication and loops was 3.5% and 7%, respectively. Mesial invagination of the root was identified in 27.8% of the samples, the majority of which contained multiple canals. CONCLUSIONS: The data obtained in this study revealed complex root morphology with high prevalence of multiple canals, more than half of which exhibited type I canal patterns. CLINICAL RELEVANCE: Micro-CT was used as a noninvasive technique for 3D investigation of root canal morphology in the mandibular first premolars of a population from southwestern China. Furthermore, data obtained revealed complex anatomy of various types. PMID- 22777391 TI - A retrospective study on the influence of maxillary canine impaction on premolar root morphology. AB - OBJECTIVES: The root morphology of the maxillary first premolar differs from the other premolars by presenting a high incidence of separated roots. This study addressed the spatial conditions during root development as a possible influencing factor. Therefore, maxillary computed tomographic (CT) scans of patients with regularly erupted or impacted permanent canines were evaluated on the root morphology of the premolars. METHODS: The following parameters were retrospectively analysed in 250 maxillary CT scans (100 patients with regular erupted permanent canines, 150 patients with at least one impacted permanent canine): sex, status of the canines (erupted/impacted), position of the impacted canines (buccal/palatal; vertically inclined inside/outside the dental arch/horizontally inclined) and root morphology of the premolars. RESULTS: Of the patients, 68% with at least one impacted canine were female; the canine was impacted palatally in 75.6% and in a horizontally inclined position in 58.4%. In patients with an impacted canine, the number of first and second premolars with separated roots was significantly reduced on the ipsilateral as well as on the contralateral side (all p values < 0.01). CONCLUSIONS: The present study detected an influence of maxillary canine impaction on the root morphology of all premolars, in that impaction and the associated surplus of space resulted in decreased root separation. This supports the hypothesis that root development is at least partly influenced by increased spatial conditions of the dental arch. However, root development can be regarded as a multifactorial event, influenced by space, direct mechanical interferences, as well as genetic predetermination. The retrospective nature of this observational study did not allow for conclusive differentiation between these factors. Alternatively, root separation and the mesial concavity of the first premolar may represent a path for canine eruption similar to the lateral incisor. CLINICAL RELEVANCE: A single-rooted maxillary first premolar might represent an additional risk factor for canine impaction. PMID- 22777393 TI - Does variation in either age at start of therapy or duration of therapy make chemoprevention with finasteride cost-effective? AB - BACKGROUND: Incremental cost-effectiveness ratios (ICERs) of finasteride for prostate cancer prevention are consistent with estimates beyond $100 000 per quality-adjusted life-year (QALY). The majority of these analyses are based on chemoprevention starting in men aged 50-55 years. We sought to evaluate the impact of varying both age at commencement of therapy and length of therapy on the cost-effectiveness of finasteride. METHODS: A probabilistic Markov model was designed to estimate lifetime prostate health-related costs and quality-adjusted survival for men receiving or not receiving chemoprevention with finasteride. ICERs across scenarios varying age at start of therapy and duration of chemoprevention were compared. RESULTS: The ICER for men starting chemoprevention at age 50 and continuing to age 75 was $88 800 per QALY when assuming finasteride causes a constant risk reduction across all tumor grades (base case 1) and $142 300 per QALY when assuming a differential treatment effect according to Gleason score (base case 2). When starting age is increased, the ICERs trend downward and nadir at 65 years to $64 700 per QALY (base case 1) and $118 600 per QALY (base case 2). Altering duration of therapy had minimal impact. Patient-level experiences with finasteride and BPH significantly influenced the cost effectiveness of chemoprevention. CONCLUSIONS: Initiating chemoprevention at ages when prostate cancer incidence is higher improves its cost-effectiveness profile. Only when assuming a constant risk reduction for all tumor grades, did finasteride fall below $100 000 per QALY, but this finding was not upheld when accounting for side effects associated with the drug. PMID- 22777392 TI - Characteristics of novel root-end filling material using epoxy resin and Portland cement. AB - OBJECTIVES: The aim of this study was to evaluate the physical properties and cytotoxicity of a novel root-end filling material (EPC) which is made from epoxy resin and Portland cement as a mineral trioxide aggregate (MTA) substitute. MATERIALS AND METHODS: EPC, developed as a root-end filling material, was compared with MTA and a mixture of AH Plus sealer and MTA (AMTA) with regard to the setting time, radio-opacity, and microleakage. Setting times were evaluated using Vicat apparatus. Digital radiographs were taken to evaluate the aluminium equivalent radio-opacity using an aluminium step wedge. Extracted single-rooted teeth were used for leakage test using methylene blue dye. After canal shaping and obturation, the apical 3-mm root was resected, and a root-end cavity with a depth of 3 mm was prepared. The root-end cavities were filled with MTA, AMTA, and EPC for 15 specimens in each of three groups. After setting in humid conditions for 24 h, the specimens were tested for apical leakage. For evaluation of the biocompatibility of EPC, cell (human gingival fibroblast) viability was compared for MTA and Portland cement by MTT assay, and cell morphological changes were compared for MTA and AH Plus by fluorescence microscopy using DAPI and F-actin staining. The setting time, radio-opacity, and microleakage were compared using one-way ANOVA and Scheffe's post hoc comparison, and the cytotoxicity was compared using the nonparametric Kruskal-Wallis rank sum test. Statistical significance was set at 95%. RESULTS: EPC had a shorter setting time and less microleakage compared with MTA (p < 0.05). EPC showed 5-mm aluminium thickness radio-opacity and similar biocompatibility to MTA. CONCLUSIONS: Under the conditions of this study, EPC, a novel composite made from a mixture of epoxy resin and Portland cement, was found to be a useful material for root-end filling, with favourable radio-opacity, short setting time, low microleakage, and clinically acceptable low cytotoxicity. CLINICAL RELEVANCE: The novel root-end filling material would be a potentially useful material for a surgical endodontic procedure with favourable properties. PMID- 22777394 TI - Low serum neutrophil count predicts a positive prostate biopsy. AB - BACKGROUND: Asymptomatic prostatic inflammation may cause increased PSA in some men, leading to unnecessary prostate biopsy. We investigated whether the differential white cell count could predict the result of prostate biopsy. METHODS: Prostate needle biopsy was carried out in 323 Japanese men with elevated PSA levels or abnormal digital rectal findings. White blood cell count (WBC), differential white cell count (neutrophils, lymphocytes, basophils, eosinophils, and monocytes), and serum C-reactive protein level were assessed for associations with biopsy findings. RESULTS: In all, 203 (62.1%) were positive for prostate cancer. WBC, neutrophil count, age, PSA, prostate volume, and PSA density (PSAD) were associated with the results of biopsy (P<0.05). Multivariate analysis showed that neutrophil count, age, PSA, prostate volume and PSAD were independent predictors. When the cut-off neutrophil count was set at 2900 MUl(-1), 78 of 104 men (75.0%) with a count below this value had a positive biopsy, while 125 of 219 (57.0%) men with a count above this value were positive. The area under the receiver-operator characteristics curve (AUC) for the predicted probability of a positive biopsy for prostate cancer according to the optimum logistic model was 0.83 (95% confidence interval (CI) 0.78-0.87), while the AUC for PSA was 0.70 (95% CI 0.64-0.76) and that for PSAD was 0.79 (95% CI 0.74-0.84). CONCLUSIONS: An elevated neutrophil count may be a good indicator of a benign prostate biopsy. Men with a low neutrophil count and an increase of serum PSA should strongly be considered for biopsy. PMID- 22777395 TI - Conflict and mental health: a cross-sectional epidemiological study in Nepal. AB - PURPOSE: The aim of this epidemiological study was to identify prevalence rates of mental health problems, factors associated with poor mental health and protective and risk factors in a post-conflict situation in Nepal. METHODS: This cross-sectional study was conducted among 720 adults in 2008. A three-stage sampling procedure was used following a proportionate stratified random sampling strategy. The outcome measures used in the study were locally validated with Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Post-Traumatic Stress Disorder (PTSD)-Civilian Version (PCL-C) and locally constructed function impairment scale, resources and coping. RESULTS: Of the sample, 27.5% met threshold for depression, 22.9% for anxiety, and 9.6% for PTSD. Prevalence rates were higher among women (depression, OR 2.14 [1.52-3.47]; anxiety, OR 2.30 [1.45 3.17] and PTSD, OR 3.32 [1.87-5.89]) and older age categories (depression, OR 1.02 [1.01-1.04]; anxiety, OR 1.04 [1.03-1.05] and PTSD, OR 1.02 [1.0-1.03]). Respondents who perceived more negative impact of the conflict (e.g., hampered the business/industry; hindered in getting medical treatment, etc.) in their communities were more at risk for depression (OR 1.1 [1.06-1.14]), anxiety (OR 1.05 [1.01-1.09]) and PTSD (OR 1.09 [1.04-1.14]). Other risk factors identified in the study were ethnicity, district of residence and poverty (lack of clothing, medicine and information via radio at home). CONCLUSION: Overall, the prevalence rates of depression and anxiety in the sample are comparable to, or lower than, other studies conducted with populations affected by conflict and with refugees. However, the findings underscore the need to address the current lack of mental health care resources in post-conflict rural Nepal, especially for marginalized populations. PMID- 22777396 TI - Emotional demands and the risks of depression among homecare workers in the USA. AB - PURPOSE: Homecare workers' diversity of emotional demands and their relation to mental health problems have not yet been fully explored. The purpose of this study is to investigate the types of emotional demands on homecare workers and the association of these demands with depression. METHOD: Data were collected from two surveys of a random sample of 1,599 homecare workers (June 2003 September 2003 and December 2003-February 2004). Depression was assessed using a 20-item RCES-D screening scale. RESULTS: Homecare workers appeared to have a variety of emotional demands: unfair treatment, client's family abuse, unmet care needs, client health, and emotional suppression. In general, homecare workers were more likely to be exposed to their client health and emotional suppression (mean scores = 1.46-3.07) than to be exposed to unmet care needs, unfair treatment, and client's family abuse (mean scores = 1.02-1.38). After adjusting for potential confounders, four emotional-demand factors (excluding the client health factor) were significantly associated with a high risk of subthreshold depression at Wave 1. In particular, the factor "unmet care needs" was an essential predictor of 6-month subthreshold depression at Wave 2. CONCLUSION: This study illustrated the diversity of emotional demands among homecare workers and their association with depression. Our mixed findings regarding the cross sectional and longitudinal analyses suggested that further research should refine the measurement of emotional demands and their relationship with mental health among homecare workers. PMID- 22777397 TI - An experience in the management of the open abdomen in severely injured burn patients. AB - Few descriptions of temporary abdominal closure for planned relaparotomy have been reported in burned patients. The purpose of this study is to describe our experience and outcomes in the management of burned patients with an open abdomen. The authors performed a retrospective review of all admissions to our burn center from March 2003 to June 2008, identifying patients treated by laparotomy with temporary abdominal closure. The authors collected data on patient demographics, indication for laparotomy, methods of temporary and definitive abdominal closure, and outcomes. Of 2,104 patients admitted, 38 underwent a laparotomy with temporary abdominal closure. Their median TBSA was 55%, and the incidence of inhalation injury was 58%. Abdominal compartment syndrome was the most common indication for laparotomy (82%) followed by abdominal trauma (16%). The in-hospital mortality associated with an open abdomen was 68%. Temporary abdominal closure was performed most commonly using negative pressure wound therapy (90%). Fascial closure was performed in 21 patients but was associated with a 38% rate of failure requiring reexploration. Of 12 survivors, fascial closure was achieved in seven patients and five were managed with a planned ventral hernia. Burned patients who necessitate an open abdomen management strategy have a high morbidity and mortality. Fascial closure was associated with a high rate of failure but was successful in a select group of patients. Definitive abdominal closure with a planned ventral hernia was associated with no increased mortality and remains an option when "tension-free" fascial closure cannot be achieved. PMID- 22777398 TI - Long-term functional outcomes in the elderly after burn injury. AB - Although the elderly represent a substantial proportion of the population, limited information exists on postdischarge long-term outcomes of elderly burn survivors. The purpose of this study was to assess elderly burn patient outcomes 2 to 10 years after discharge. This study was a prospective cross-sectional survey assessment of quality of life and retrospective trauma registry for the American College of Surgeons review of patients >= 60 years of age discharged alive after acute burn from 1997 to 2007. In-hospital treatment and burn demographic information were obtained from database and chart review. Surviving patients or their families were contacted, and the Short-Form-12 and Functional Independence Measure (FIM) administered. Of the 344 patients discharged, 232 participated. Mean age was 72.3 (60-85.8) years, TBSA burn was 7.8% (1-79), and length of stay was 11.2 +/- 0.9 days (1-51). Most patients were discharged home (71%) or to a skilled nursing facility (SNF; 20%). Mean interval between discharge and survey administration was 46.1 months. In all, 24% of patients sent home died after discharge and prior to interview compared with 58% of patients sent to an SNF. On multivariate analysis, mortality increased with age (confidence interval [CI] 1.04-1.09), and government insurance (CI 0.34-0.94), but decreased with discharge to home (CI 1.68-4.47). There were no differences in FIM or Short-Form-12 scores between groups. Long-term mortality after discharge in elderly burn survivors is substantial. Patients sent to an SNF or with government insurance had increased mortality postdischarge. These data suggest that issues that may influence disposition status of elderly burn patients should be optimized prior to discharge to mitigate adverse outcomes associated with SNF placement. PMID- 22777399 TI - Strategies for molecular classification of asthma using bipartite network analysis of cytokine expression. AB - Asthma is a chronic inflammatory disease of the airways that leads to various degrees of recurrent respiratory symptoms affecting patients globally. Specific subgroups of asthma patients have severe disease leading to increased healthcare costs and socioeconomic burden. Despite the overwhelming prevalence of the asthma, there are limitations in predicting response to therapy and identifying patients who are at increased risk of morbidity. This syndrome presents with common clinical signs and symptoms; however, awareness of subgroups of asthma patients with distinct characteristics has surfaced in recent years. Investigators attempt to describe the phenotypes of asthma to ultimately assist with diagnostic and therapeutic applications. Approaches to asthma phenotyping are multifold; however, it can be partitioned into 2 essential groups, clinical phenotyping and molecular phenotyping. Innovative techniques such as bipartite network analysis and visual analytics introduce a new dimension of data analysis to identify underlying mechanistic pathways. PMID- 22777400 TI - Differential regulation by Toll-like receptor agonists reveals that MCPIP1 is the potent regulator of innate immunity in bacterial and viral infections. AB - Toll-like receptors (TLRs) are key molecules in innate immunity that recognize a variety of pathogen-associated molecular patterns. Activation of TLRs by their agonists initiates several signaling cascades, which eventually result in the expression of immune modifiers. Despite the fact that MCPIP1 is reported as an important immune regulator involved in macrophage activation, modulation of its expression by all known TLR agonists has never been documented. In this study, we present for the first time that in human monocyte-derived macrophages all TLR agonists, except CpG, markedly induced the expression of MCPIP1. The level of the induced transcript, as well as the protein and time of their appearance varied depending on the agonist. Furthermore, we confirmed the strong and differential upregulation of MCPIP1 during bacteria, virus and fungus infection. MCPIP1 belongs to a group of early-response genes; however, in the present study, we show for the first time the sustained high level of MCPIP1 expression during long term Staphylococcus aureus infection. Taken together, our results implicate MCPIP1 as a potent regulator of innate immunity, which can be strongly engaged in the pathogenesis of acute and chronic infective diseases. PMID- 22777403 TI - Epilepsy in Sardinia, insular Italy: a population-based prevalence study. AB - BACKGROUND: Sardinia, insular Italy, represents a particular epidemiological setting to investigate polyfactorial diseases, by virtue of its phylogeny and geographic isolation over time and of a well-established network of health operators and information systems. We present the first prevalence study of epilepsy conducted on a large Sardinian population by means of multiple source ascertainment. METHODS: Cases were ascertained in the province of Sassari (population of 333,576) for the period between January 1, 2000 and December 31, 2008 based on records from (a) the District Center for Epilepsy, (b) the District Health Information System Unit, and (c) the neurologists practicing within the National Health System. RESULTS: The total crude prevalence of active epilepsy on December 31, 2007 was 6.62 per 1,000 (95% CI 5.3-7.9), 6.51 in men (95% CI 5.4 7.6), and 6.73 in women (95% CI 5.7-7.7). The highest prevalence (8.78 per 1,000) was estimated in the elderly (>=65 years). 50.5% were symptomatic epilepsies. Of these, over 50% were secondary to cerebrovascular disorders in the elderly. CONCLUSIONS: The epidemiological behavior of prevalence of active epilepsy in Sardinia appears to be in line with that of other developed countries, despite the role that population-specific genetic and environmental factors exert in modulating the risk for other neurological diseases. The action of (exogenous) factors commonly distributed in western populations, also influencing, at least partially, the epidemiological patterns of epilepsy in Sardinians, should not be ruled out. PMID- 22777402 TI - Potential inhibitory effect of LASSBio-596, a new thalidomide hybrid, on inflammatory corneal angiogenesis in rabbits. AB - AIMS: Evaluate the effect of LASSBio-596, structurally designed as a new hybrid of thalidomide, on inflammatory corneal angiogenesis. METHODS: Eighteen rabbits were submitted to an alkaline cauterization in the right cornea. The animals were randomly allocated to three groups: vehicle, dexamethasone and LASSBio-596. Drugs were administered by eyedrops 3 times a day for 21 days. Evaluations were performed on days 3, 6, 9, 12, 15, 18 and 21 after cauterization. At these time points, digital images of the cornea were captured in a standard fashion. The angiogenic response was measured using software that was developed specifically for this purpose. It calculated the following parameters: neovascularization area (NA), total vascular length (TVL) and blood vessel number (BVN). RESULTS: It was observed that dexamethasone significantly decreased NA, TVL and BVN during all assessments. From the NA the angiogenesis rate (AR) was calculated in each group. Therefore, dexamethasone completely inhibited the inflammatory corneal angiogenesis with an AR of -0.001 +/- 0.006 mm(2)/day, which was significantly lower (p < 0.001) than that observed after treatment with vehicle (0.078 +/- 0.024 mm(2)/day) and LASSBio-596 (0.054 +/- 0.012 mm(2)/day). Although LASSBio 596 reduced angiogenesis in relation to vehicle, according to NA, TVL and BVN values, this difference was not statistically significant. However, it was found that the AR as measured in the LASSBio-596 group was significantly lower (p < 0.05) than that seen in control animals, indicating a potential antiangiogenic effect. CONCLUSION: We conclude that topical application of LASSBio-596 at 1.0% has a potential inhibitory effect on inflammatory corneal angiogenesis in rabbits. PMID- 22777404 TI - Progressive development of Chiari I malformation in a child with trilateral retinoblastoma and acquired growth hormone deficiency. PMID- 22777405 TI - The effects of the Palliative Medicine Consultation on the DNR status of African Americans in a safety-net hospital. AB - OBJECTIVE: To examine the effectiveness of palliative medicine consultation on completion of advance directives/do-not-resuscitate (DNR) orders by racial/ethnic minorities. METHOD: A sample of 1999 seriously ill African American and Hispanic inpatients was obtained from the Palliative Medicine Consultation database (n = 2972). Associations between race/ethnicity and diagnosis and documentation of DNR status on admission and discharge were examined. RESULTS: Cancer was the primary diagnosis, 34.5%. Among patients with a consultation, 98% agreed to discuss advance directives; 65% of African Americans and 70% of Hispanics elected DNR status. Inpatient deaths were 46%; 74% of decedents agreed to DNR orders. Discharged patients referred to hospice were 29%. CONCLUSION: Palliative medicine consultations resulted in timely completion of DNR orders and were positively associated with DNR election and hospice enrollment. PMID- 22777406 TI - Surrogates with conflicting interests: who makes the decision? PMID- 22777407 TI - Shifting hospital-hospice boundaries: historical perspectives on the institutional care of the dying. AB - Social forces have continually framed how hospitals perceive their role in care of the dying. Hospitals were originally conceived as places of hospitality and spiritual care, but by the 18th century illness was an opponent, conquered through science. Medicalization transformed hospitals to places of physical cure and scientific prowess. Death was an institutional liability. Equipped with new technologies, increased public demand, and the establishment of Medicare in 1965, modern hospitals became the most likely place for Americans to die--increasing after the 1940s and spiking in the 1990s. Medicare's 1983 hospice benefit began to reverse this trend. Palliative care has more recently proliferated, suggesting an institutional shift of alignment with traditional functions of care toward those facing death. PMID- 22777408 TI - Impact of an oncology palliative care clinic on access to home care services. AB - Home care (HC) is important for patients with cancer as performance status declines. Our study of 1224 patients at a Canadian cancer center examined the impact of an oncology palliative care clinic (OPCC) on HC referral. The HC referral frequency was calculated before and after the first OPCC consultation, in total and according to performance status (Palliative Performance Scale, PPS). Characteristics associated with HC referral were investigated. After the first OPCC consultation, there was an increase in HC referral from 39% (477 of 1224; 49% of those with PPS <=60) to 69% (841 of 1224; 88% of those with PPS <=60). Factors independently associated with HC referral were poor PPS (P < .001) and older age (P = .003). Thus OPCC involvement resulted in markedly increased HC referrals, particularly for older patients with poor performance status. PMID- 22777409 TI - The evaluation of the relationship between the level of disclosure of cancer in terminally ill patients with cancer and the quality of terminal care in these patients and their families using the Support Team Assessment Schedule. AB - AIMS: To examine the relationship between informing patients of cancer and the quality of terminal care. METHODS: This was a study of 87 consecutive terminally ill cancer patients who died during the last 27-month period. Notification of cancer was classified into 4 groups (A, B, C, and D, respectively): "nondisclosure," "disclosure of cancer diagnosis," "disclosure of life threatening," and "disclosure of poor prognosis." We evaluated the quality of palliative care using Support Team Assessment Schedule-Japanese (STAS-J). RESULTS: A, B, C, and D groups included 8, 22, 37, and 20 cases, respectively. Regarding physical symptoms, no marked difference was noted. Anxiety was significantly reduced, and the recognition of disease conditions and the level of communication were significantly higher in the groups that received specific information (P < .001). CONCLUSIONS: Informing patients of more specific information will increase the quality of terminal care. PMID- 22777410 TI - Prevalence of methicillin-resistant Staphylococcus aureus colonization and infection in hospitalized palliative care patients with cancer. AB - Little is known about the pattern of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in hospitalized palliative care (PC) patients. We reviewed 854 admissions for 289 patients with advanced cancer managed by a PC service in a tertiary care hospital. The MRSA screening was performed at least once in 228 (79%) patients, and 21 (9%) of them were MRSA positive. Other cultures were done in 251 (86.8%) patients, and 8 (3%) patients were MRSA positive. The total number of MRSA-positive admissions was 28 (3%), with a median admission duration of 8 days. A substantial proportion of hospitalized PC patients with cancer are MRSA positive. Research is required to study the impact of infection control measures on the quality of PC delivered to MRSA-positive terminally ill patients in hospitals. PMID- 22777411 TI - An observational study of insomnia and nightmare treated with trazodone in patients with advanced cancer. AB - Patients with cancer often experience insomnia. Nightmares are also a strong factor that interferes with the maintenance of comfortable and satisfying sleep. However, the prevalence and standard treatment of nightmares in patients with cancer have not been established yet. We aimed to treat insomnia and nightmares with trazodone. From 2008 to 2011, trazodone was prescribed to 30 patients with cancer who reported experiencing insomnia with or without nightmares to the palliative care team in Osaka University Hospital. Effective treatment was seen in 15 patients (50%). Four patients with cancer reported having severe nightmares and 2 patients had beneficial effects, with frightening dreams transformed into acceptable ones. Trazodone may be an effective drug for the treatment of insomnia and nightmares in patients with advanced cancer. PMID- 22777412 TI - Prevalence and management of pain by different age groups of Korean cancer patients. AB - The aims of this study were to evaluate the differences in cancer prevalence and pain management between young and elderly patients. The patients were grouped into 3 groups. The prevalence of cancer pain was 50.0% in those younger than 65 years, 55.9% in those aged between 65 and 75, and 58.3% in those older than 75 years. The prevalence of cancer pain was higher for patients in advanced stages and with poor performance status. Using logistic regression analysis, we found that performance status has a significant correlation with cancer pain. Severe cancer pain occurred in 8.0% of the patient and was most prevalent in the advanced stage. Side effects of analgesics were observed in 24.5%. Cancer pain correlates with performance status and cancer stage but not significantly with age. PMID- 22777413 TI - Volunteer orthopedic surgical trips in Nicaragua: a cost-effectiveness evaluation. AB - BACKGROUND: Injuries account for a substantial portion of the world's burden of disease and require effective surgical care. Volunteer surgical teams that form partnerships with hospitals help build local surgical capacity while providing immediate care. The purpose of the present study was to evaluate the cost effectiveness of short orthopedic surgical volunteer trips as a method of reducing the global burden of surgical disease through both surgical and educational interventions. METHODS: Data were collected from a scheduled volunteer trip to Leon, Nicaragua, in January 2011 as part of the Cooperacion Ortopedica Americano Nicaraguense (COAN), a 501c3 nonprofit organization established in 2002. Costs are from the COAN provider prospective with an additional analysis to include the Nicaraguan provider variable costs. The total burden of musculoskeletal disease averted from the patients receiving surgical intervention was derived using the disability-adjusted-life-years (DALYs) framework and disability weights from the disease control priority project. The cost-effectiveness ratio was calculated by dividing the total costs by the total DALYs averted. RESULTS: A total of 44.78 DALYs were averted in this study, amounting to an average of 1.49 DALYs averted per patient. The average cost per patient from the COAN provider perspective was $525.64, and from both the COAN and Nicaraguan provider perspective it was $710.97. In the base case, cost effectiveness was $352.15 per DALY averted, which is below twice the Nicaraguan per capita gross national income ($652.40). CONCLUSIONS: Volunteer orthopedic surgical trips are cost-effective in Nicaragua. Further research should be conducted with multiple trips and with different patient populations to test the generalizability of the results. PMID- 22777414 TI - A comparison of laparoscopic cholecystectomy for acute cholecystitis both within and beyond 72 h of symptom onset during the emergency admission: how golden is "golden"? PMID- 22777415 TI - Development of a formula to predict parathyroid carcinoma in patients with primary hyperparathyroidism. AB - BACKGROUND: Cure of parathyroid carcinoma (PC) requires initial en bloc resection, including resection of all tumor-bearing tissue, with hemithyroidectomy and dissection of the central lymph node compartment. Unfortunately, no reliable preoperative criteria have yet been assessed to indicate a high likelihood of PC. Thus, the aim of the present study was to develop a formula to indicate preoperatively the presence of PC. METHODS: A prospective database of 1,363 patients with primary hyperparathyroidism (pHPT) was screened for patients with PC. Age, gender, surgical procedures, laboratory data, and follow-up results were evaluated and compared to a group of patients with benign pHPT. Based on preoperative serum calcium (Ca) and parathyroid hormone (PTH) levels, as well as patients' age at the time of diagnosis, a formula was developed by a multivariate logistic model that estimates the individual risk for PC. RESULTS: Between 1987 and 2008, 19 patients with PC were identified. Ca (3.8 +/- 0.3 vs 2.9 +/- 0.3 mmo/l; p = 0.0002) and PTH levels (1,250 +/- 769 vs 194 +/- 204 pg/ml; p = 0.0030) were significantly higher in patients with PC than in those with benign pHPT. Patients with PC were also significantly younger than patients with benign pHPT (48.9 +/- 12.1 vs 59.1 +/- 13.8 years; p < 0.05). With a >=5 % probability that a given patient suffered from PC, the sensitivity and specificity to identify the disease were 100 and 30 %, respectively, with the new Ca, PTH, and age based logarithmic formula. CONCLUSIONS: The new logarithmic formula can be used to calculate the individual risk for PC. If the calculated individual risk exceeds 5 %, en bloc resection seems to be justified to provide long-term cure in case of PC. PMID- 22777416 TI - Regenerative surgery: tissue engineering in general surgical practice. AB - Tissue engineering is a broad interdisciplinary field that aims to develop complex tissue and organ constructs through a combination of cell-, biomaterial-, and molecular-based approaches. This approach has the potential to transform the surgical treatment for diseases including trauma, cancer, and congenital malformations. A fundamental knowledge of key concepts in regenerative medicine is imperative for surgeons to maintain a leading role in developing and implementing these technologies. Researchers have started to elucidate the biologic mechanisms that maintain organ homeostasis throughout life, indicating that humans may have the latent capacity to regenerate complex tissues. By exploiting this intrinsic potential of the body, we can move even closer to developing functional, autologous replacement parts for a wide range of surgical diseases. PMID- 22777417 TI - Focal but reversible diastolic sheet dysfunction reflects regional calcium mishandling in dystrophic mdx mouse hearts. AB - Cardiac dysfunction is a primary cause of patient mortality in Duchenne muscular dystrophy, potentially related to elevated cytosolic calcium. However, the regional versus global functional consequences of cellular calcium mishandling have not been defined in the whole heart. Here we sought for the first time to elucidate potential regional dependencies between calcium mishandling and myocardial fiber/sheet function as a manifestation of dystrophin-deficient (mdx) cardiomyopathy. Isolated-perfused hearts from 16-mo-old mdx (N = 10) and wild type (WT; N = 10) were arrested sequentially in diastole and systole for diffusion tensor MRI quantification of myocardial sheet architecture and function. When compared with WT hearts, mdx hearts exhibited normal systolic sheet architecture but a lower diastolic sheet angle magnitude (|beta|) in the basal region. The regional diastolic sheet dysfunction was normalized by reducing perfusate calcium concentrations. Optical mapping of calcium transients in isolated hearts (3 mdx and 4 WT) revealed a stretch-inducible regional defect of intracellular calcium reuptake, reflected by a 25% increase of decay times (T(50)) and decay constants, at the base of mdx hearts. The basal region of mdx hearts also exhibited greater fibrosis than did the apex, which matched the regional sheet dysfunction. We conclude that myocardial diastolic sheet dysfunction is observed initially in basal segments along with calcium mishandling, ultimately culminating in increased fibrosis. The preservation of relatively normal calcium reuptake and diastolic/systolic sheet mechanics throughout the rest of the heart, together with the rapid reversibility of functional defects by reducing cytosolic calcium, points to the significance of regional mechanical factors in the progression of the disease. PMID- 22777420 TI - Gene and cytokine therapy for heart failure: molecular mechanisms in the improvement of cardiac function. AB - Despite significant advances in pharmacological and clinical treatment, heart failure (HF) remains a leading cause of morbidity and mortality worldwide. Many new therapeutic strategies, including cell transplantation, gene delivery, and cytokines or other small molecules, have been explored to treat HF. Recent advancement of our understanding of the molecules that regulate cardiac function uncover many of the therapeutic key molecules to treat HF. Furthermore, a theory of paracrine mechanism, which underlies the beneficial effects of cell therapy, leads us to search novel target molecules for genetic or pharmacological strategy. Gene therapy means delivery of genetic materials into cells to achieve therapeutic effects. Recently, gene transfer technology in the cardiovascular system has been improved and several therapeutic target genes have been started to examine in clinical research, and some of the promising results have been emerged. Among the various bioactive reagents, cytokines such as granulocyte colony-stimulating factor and erythropoietin have been well examined, and a number of clinical trials for acute myocardial infarction and chronic HF have been conducted. Although further research is needed in both preclinical and clinical areas in terms of molecular mechanisms, safety, and efficiency, both gene and cytokine therapy have a great possibility to open the new era of the treatment of HF. PMID- 22777419 TI - A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture. AB - The role of microcalcifications (MUCalcs) in the biomechanics of vulnerable plaque rupture is examined. Our laboratory previously proposed (Ref. 44), using a very limited tissue sample, that MUCalcs embedded in the fibrous cap proper could significantly increase cap instability. This study has been greatly expanded. Ninety-two human coronary arteries containing 62 fibroatheroma were examined using high-resolution microcomputed tomography at 6.7-MUm resolution and undecalcified histology with special emphasis on calcified particles <50 MUm in diameter. Our results reveal the presence of thousands of MUCalcs, the vast majority in lipid pools where they are not dangerous. However, 81 MUCalcs were also observed in the fibrous caps of nine of the fibroatheroma. All 81 of these MUCalcs were analyzed using three-dimensional finite-element analysis, and the results were used to develop important new clinical criteria for cap stability. These criteria include variation of the Young's modulus of the MUCalc and surrounding tissue, MUCalc size, and clustering. We found that local tissue stress could be increased fivefold when MUCalcs were closely spaced, and the peak circumferential stress in the thinnest nonruptured cap (66 MUm) if no MUCalcs were present was only 107 kPa, far less than the proposed minimum rupture threshold of 300 kPa. These results and histology suggest that there are numerous MUCalcs < 15 MUm in the caps, not visible at 6.7-MUm resolution, and that our failure to find any nonruptured caps between 30 and 66 MUm is a strong indication that many of these caps contained MUCalcs. PMID- 22777418 TI - Acute O-GlcNAcylation prevents inflammation-induced vascular dysfunction. AB - Acute increases in cellular protein O-linked N-acetyl-glucosamine (O-GlcNAc) modification (O-GlcNAcylation) have been shown to have protective effects in the heart and vasculature. We hypothesized that d-glucosamine (d-GlcN) and Thiamet-G, two agents that increase protein O-GlcNAcylation via different mechanisms, inhibit TNF-alpha-induced oxidative stress and vascular dysfunction by suppressing inducible nitric oxide (NO) synthase (iNOS) expression. Rat aortic rings were incubated for 3h at 37 degrees C with d-GlcN or its osmotic control l glucose (l-Glc) or with Thiamet-G or its vehicle control (H(2)O) followed by the addition of TNF-alpha or vehicle (H(2)O) for 21 h. After incubation, rings were mounted in a myograph to assess arterial reactivity. Twenty-four hours of incubation of aortic rings with TNF-alpha resulted in 1) a hypocontractility to 60 mM K(+) solution and phenylephrine, 2) blunted endothelium-dependent relaxation responses to ACh and substance P, and 3) unaltered relaxing response to the Ca(2+) ionophore A-23187 and the NO donor sodium nitroprusside compared with aortic rings cultured in the absence of TNF-alpha. d-GlcN and Thiamet-G pretreatment suppressed the TNF-alpha-induced hypocontractility and endothelial dysfunction. Total protein O-GlcNAc levels were significantly higher in aortic segments treated with d-GlcN or Thiamet-G compared with controls. Expression of iNOS protein was increased in TNF-alpha-treated rings, and this was attenuated by pretreatment with either d-GlcN or Thiamet-G. Dense immunostaining for nitrotyrosylated proteins was detected in the endothelium and media of the aortic wall, suggesting enhanced peroxynitrite production by iNOS. These findings demonstrate that acute increases in protein O-GlcNAcylation prevent TNF-alpha induced vascular dysfunction, at least in part, via suppression of iNOS expression. PMID- 22777421 TI - A lumped parameter model of cerebral blood flow control combining cerebral autoregulation and neurovascular coupling. AB - Cerebral blood flow regulation is based on a variety of different mechanisms, of which the relative regulatory role remains largely unknown. The cerebral regulatory system expresses two regulatory properties: cerebral autoregulation and neurovascular coupling. Since partly the same mechanisms play a role in cerebral autoregulation and neurovascular coupling, this study aimed to develop a physiologically based mathematical model of cerebral blood flow regulation combining these properties. A lumped parameter model of the P2 segment of the posterior cerebral artery and its distal vessels was constructed. Blood flow regulation is exerted at the arteriolar level by vascular smooth muscle and implements myogenic, shear stress based, neurogenic, and metabolic mechanisms. In eight healthy subjects, cerebral autoregulation and neurovascular coupling were challenged by squat-stand maneuvers and visual stimulation using a checkerboard pattern, respectively. Cerebral blood flow velocity was measured using transcranial Doppler, whereas blood pressure was measured by finger volume clamping. In seven subjects, the model proposed fits autoregulation and neurovascular coupling measurement data well. Myogenic regulation is found to dominate the autoregulatory response. Neurogenic regulation, although only implemented as a first-order mechanism, describes neurovascular coupling responses to a great extent. It is concluded that our single, integrated model of cerebral blood flow control may be used to identify the main mechanisms affecting cerebral blood flow regulation in individual subjects. PMID- 22777422 TI - Layer-specific strain analysis: investigation of regional deformations in a rat model of acute versus chronic myocardial infarction. AB - Myocardial infarction (MI) injury extends from the endocardium toward the epicardium. This phenomenon should be taken into consideration in the detection of MI. To study the extent of damage at different stages of MI, we hypothesized that measurement of layer-specific strain will allow better delineation of the MI extent than total wall thickness strain at acute stages but not at chronic stages, when fibrosis and remodeling have already occurred. After baseline echocardiography scans had been obtained, 24 rats underwent occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion. Thirteen rats were rescanned at 24 h post-MI and eleven rats at 2 wk post-MI. Next, rats were euthanized, and histological analysis for MI size was performed. Echocardiographic scans were postprocessed by a layer-specific speckle tracking program to measure the peak circumferential strain (S(C)(peak)) at the endocardium, midlayer, and epicardium as well as total wall thickness S(C)(peak). Linear regression for MI size versus S(C)(peak) showed that the slope was steeper for the endocardium compared with the other layers (P < 0.001), meaning that the endocardium was more sensitive to MI size than the other layers. Moreover, receiver operating characteristics analysis yielded better sensitivity and specificity in the detection of MI using endocardial S(C)(peak) instead of total wall thickness S(C)(peak) at 24 h post-MI (P < 0.05) but not 2 wk later. In conclusion, at acute stages of MI, before collagen deposition, scar tissue formation, and remodeling have occurred, damage may be nontransmural, and thus the use of endocardial S(C)(peak) is advantageous over total wall thickness S(C)(peak). PMID- 22777423 TI - Taking a bite out of Wnts. AB - Proper control of intercellular communication through the Wnt signaling pathway is of critical importance for many aspects of biology, including head formation during vertebrate embryogenesis. A recent Cell paper describes the discovery of a novel protein, TIKI, which controls head size through a surprising new mechanism of Wnt antagonism. PMID- 22777424 TI - Mechanisms involved in the Abacavir-mediated hypersensitivity syndrome. AB - The potentially life-threatening adverse reactions to Abavacir (ABC), a nucleoside analog reverse transcriptase inhibitor for the treatment of HIV infection, have been known for several years to be limited to individuals expressing the HLA-B57:01 gene. Why the ABC hypersensitivity syndrome is only seen in HLA-B57:01-expressing subjects and what the precise mechanisms underlying this intolerance are remain however controversial. A series of recent studies, particularly a study by Illing et al. recently published in Nature, now answer some of these questions and offer new opportunities to better understand autoimmune disorders and prevent adverse reactions to other drugs. PMID- 22777425 TI - Pull and push: talin activation for integrin signaling. AB - The inside-out signaling of integrins regulates the ligand-binding affinity of the cell surface receptors in response to changes in the environment for cell survival. The specific binding to the cytoplasmic tail of integrin's beta subunit by the intracellular protein talin is the key step of inside-out signaling. A "pull-push" mechanism has been proposed to explain how the PIP2-enriched membrane disrupts the dual auto-inhibition of the N-terminal talin-FERM domain by the C terminal talin-rod domain such that activated talin-FERM can reach the beta-tail for integrin activation. PMID- 22777426 TI - Improving preterm ophthalmologic care in the era of accountable care organizations. AB - OBJECTIVES To understand retinopathy of prematurity (ROP) follow-up care for preterm very low-birth-weight infants (VLBW; <1500 g) in the context of the chronic care model and identify opportunities for improvement under accountable care organizations. METHODS We conducted focus groups and interviews with parents (N = 47) of VLBW infants and interviews with neonatal intensive care unit and ophthalmologic providers (N = 28) at 6 sites in Massachusetts and South Carolina. Themes are reported according to consolidated criteria for reporting qualitative research guidelines. RESULTS Respondents perceived that legal liability and low reimbursement contributed to shortages of ROP providers. Some neonatal intensive care units offered subsidies to attract ophthalmologic providers or delayed transfers to institutions that could not provide ROP examinations and/or treatment. Sites used variable practices for coordinating ROP care. Even at sites with a tracking database and a dedicated ROP coordinator, significant time was required to ensure that examinations and treatment occurred as scheduled. Parents' ability to manage their children's health care was limited by parental understanding of ROP, feeling overwhelmed by the infant's care, and unmet needs for resources to address social stressors. CONCLUSIONS Under accountable care organizations, hospitals and ophthalmology practices should share responsibility for ensuring coordinated ROP care to mitigate liability concerns. To promote integrated care, reimbursement for ROP care should be bundled to include screening, diagnosis, treatment, and appropriate follow-up. Clinical information systems should be enhanced to increase efficiency and limit lapses in care. Self management tools and connections to community resources could help promote families' attendance of follow-up appointments. PMID- 22777427 TI - Comparative study of the relaxation mechanisms of the excited states of cytosine and isocytosine. AB - An experimental and theoretical investigation was performed to study the photostability of cytosine and isocytosine. The experimental UV irradiation of acetonitrile solutions of the two compounds showed that the amino-oxo tautomer of cytosine is photostable while the amino-oxo tautomer of isocytosine tautomerizes to the amino-hydroxy form. The theoretical investigations were carried out at the CC2 level of theory. They were performed to explain the experimental observations. It was found that the (1)pipi(*) excited states of the ring deformation mechanisms of cytosine and isocytosine relax (internal conversion) to the ground states of the amino-oxo forms of the compounds. We propose a channel for the radiationless deactivation of the repulsive (1)pisigma(*) excited state of the amino-oxo form of isocytosine to the ground state of the amino-hydroxy tautomer. PMID- 22777428 TI - Theoretical investigations on the structure, density, thermodynamic and performance properties of amino-, methyl-, nitroso- and nitrotriazolones. AB - We have studied herein the effect of position and the number of -NO, -NO2, -NH2 and -CH3 groups on the structure, stability, impact sensitivity, density, thermodynamic and detonation properties of triazolones by performing density functional theory calculations at the B3LYP/aug-cc-pVDZ level. The optimized structures, vibrational frequencies and thermodynamic values for triazolones have been obtained in their ground state. Kamlet-Jacob equations were used to calculate the detonation velocity and detonation pressure of model compounds. The detonation properties of NNTO (D 8.75 to 9.10 km/s, P 34.0 to 37.57 GPa), DNTO (D 8.80 to 9.05 km/s, P 35.55 to 38.27 GPa), ADNTO (D 9.01 to 9.42 km/s and P 37.81 to 41.10 GPa) and ANNTO (D 8.58 to 9.0 km/s, P 30.81 to 36.25 GPa) are compared with those of 1,3,5-trinitro-1,3,5-triazine (RDX) (D 8.75 km/s, P 34.70 Gpa) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) (D 8.96 km/s, P 35.96 GPa). The designed compounds satisfy the criteria of high energy materials. PMID- 22777429 TI - Insight into shock-induced chemical reaction from the perspective of ring strain and rotation of chemical bonds. AB - Density functional theory BLYP/DNP and hyperhomodesmotic equations were employed to calculate ring strain energy, the bond dissociation energy of X-NO(2) (X=C, N) and the charges on the nitro groups of several four-membered and six-membered heterocycle compounds. BLYP/DNP and LST/QST + CG method were also applied to calculate bond rotational energy of X-NO(2) (X=C, N) of above mentioned compounds. It indicated that ring strain energy of four-membered heterocycle nitro compounds is apparently higher than that of six-membered heterocycle nitro compounds. Predictably, ring-opening reactions may preferentially occur for those compounds containing higher ring strain energy under shock. In addition, C-NO(2) bonds in these compounds may rotate easier than N-NO(2) bonds in response to the external shock. As for N-NO(2) bonds in these compounds, they also respond to the external shock by the rotation of N-NO(2) bonds, once to the saddle point of the rotational energy barrier, the whole molecule will become relaxed, N-NO(2) bond becomes weaker and eventually leads to the breakage. When one -C=O, -C=NH or NH(2) group is introduced to the six-membered heterocycle, the charges on the nitro groups of the new compound decrease drastically, and ring strains increase remarkably. It can be predicted that the new compounds will be more sensitive to shock, and the viewpoint is confirmed by the experimental results of shock sensitivity (small scale gap test) of several explosives. PMID- 22777431 TI - New approach for the surgico-orthodontic treatment of hemifacial microsomia. AB - One of the important clinical findings in hemifacial microsomia (HFM) is facial asymmetry (FA) with unilateral underdevelopment and malformation of the mandible and/or maxilla. Unilateral distraction osteogenesis (UDOG) of the mandible has been used for correction of FA in HFM patients. However, return to the original FA status often occurs because of contraction of the distracted bony segment of the mandible and insufficient compensatory downward growth and skeletal midline correction of the maxilla on the affected side. Although bimaxillary UDOG procedure in the maxilla with Le Fort I osteotomy and the mandible with ramus osteotomy was suggested as an alternative treatment modality, it has some disadvantages including elongation of the face, inaccuracy of vector control, and less predictable results. Occlusal plane canting, skeletal midline deviation of the maxilla, and unilateral mandibular hypoplasia might be simultaneously corrected by fixation of the maxilla into a proper position after Le Fort I osteotomy and UDOG of the mandible. Three-dimensional virtual simulation using three-dimensional computed tomography data could help to accurately predict surgical outcomes. In addition, transarch elastic traction from the orthodontic mini-implants on the unaffected side of the mandible to the maxillary posterior teeth on the affected side can produce a plastic molding of the regenerated bone in the distraction area of the mandible and induce compensatory dentoalveolar downward development of the maxillary posterior teeth. Therefore, the purpose of this article was to introduce a new approach for the surgico-orthodontic treatment consisting of simultaneous maxillary fixation and unilateral mandibular distraction with transarch elastic traction in HFM patients. PMID- 22777430 TI - No islets left behind: islet autotransplantation for surgery-induced diabetes. AB - For patients with severe chronic pancreatitis refractory to medical interventions, total pancreatectomy can be considered to relieve the root cause of pain. The goal of a simultaneous islet autotransplant is to prevent or minimize the otherwise inevitable surgical diabetes. Islet autotransplant can successfully preserve some endogenous islet function in the majority of recipients, which mediates protection against brittle diabetes. Most maintain reasonably good glycemic control, while 30 %-40 % successfully discontinue insulin therapy. With islet autotransplants reaching a wider clinical audience, refinements in islet isolation techniques and strategies to protect islet grafts post-transplant may further improve the success of this procedure. PMID- 22777432 TI - Comparative analysis of the nail xenografts with cartilage autografts in eyelid reconstruction. AB - OBJECTIVE: The tarsal plate is the skeleton support system of the eyelids; therefore, repair during eyelid reconstruction is crucial. Many autogenous graft materials have been proposed for the tarsal reconstruction, such as nasal cartilage, palatal mucosa, upper eyelid tarsus, and auricular cartilage. Nail thickness and shape are similar to the tarsal plate with enough support for the eyelid. It also easily integrates with host tissues. The aim of this experimental study was to macroscopically and histopathologically compare nail xenografts with cartilage autografts when used in eyelid reconstruction in rabbits. METHODS: In total, 12 New Zealand rabbits were used in the experiment. Full-thickness defect with a 1-cm diameter was created in both upper eyelids. The right upper eyelids were used for cartilage autograft reconstruction, and the left upper eyelids were used for nail xenograft reconstruction. All animals were killed on week 12 after eyelid reconstruction. After the animals were killed, the upper eyelids of the rabbits were resected for macroscopic and histologic analysis. RESULTS: In histologic evaluation, moderate foreign body giant cell formation and moderate histiocytic, neutrophilic, basophilic, and lymphocytic infiltration were observed in both experimental group and control group. In addition, this marked fibrous capsule formation was observed around the nail xenograft, which was absent in the cartilage autograft group. CONCLUSIONS: Nail has some advantages such as being cost-effective, being easy to obtain, and having less rejection risk for being composed of dead cells. Nail xenografts can be taken into account instead of cartilage grafts in eyelid reconstruction. PMID- 22777433 TI - Effects of lidocaine plus epinephrine and prilocaine on autologous fat graft survival. PMID- 22777434 TI - Clinical effectiveness of monocanalicular and bicanalicular silicone intubation for congenital nasolacrimal duct obstruction. AB - BACKGROUND: Numerous surgical techniques of silicone tube intubation in congenital nasolacrimal duct obstruction (CNLDO) have been described; these techniques can be divided into monocanalicular intubation (MCI) and bicanalicular intubation (BCI). The aim of this study was to compare the clinical effectiveness of MCI versus BCI of CNLDO. METHODS: In a prospective, nonrandomized, comparative case study, patients with CNLDO underwent probing under endoscopic control and either BCI or MCI under general anesthesia. Demographic data, including age and sex, duration of preoperative symptoms, method of previous treatment, operative time, timing of silicone tube removal, follow-up periods, complications, and outcomes, were analyzed. RESULTS: The study included 30 eyes from 22 patients for BCI and 30 eyes from 24 patients for MCI. The mean age in the BCI group was 23.3 months and in the MCI group was 23.1 months. Mean follow-up was 16.4 +/- 5.9 weeks for BCI group and 11.6 +/- 8.2 weeks for MCI group. Operation time was slightly longer in the BCI group. Tubes were most often removed in the operating room under general anesthesia for BCI (66.7%) and in an office setting under topical anesthesia for MCI (100%). Overall, BCI had a 93.3% success rate (28/30), and MCI had a 90.0% success rate (27/30). CONCLUSIONS: Although there was no significant difference between the success rates of the 2 groups, MCI allowed technical ease of insertion and tube removal. Moreover, the tubing does not threaten the unprobed part of the lacrimal drainage system. These advantages of MCI should be considered when selecting treatment methods for CNLDO. PMID- 22777435 TI - Fracture depth and delayed contour deformity in frontal sinus anterior wall fracture. AB - OBJECTIVES: The choice to manage isolated frontal sinus anterior wall fractures without the involvement of nasofrontal outflow tract is mainly based on aesthetic concern and depends largely on surgeons' preferences. Minimally depressed anterior wall fractures can be monitored by observation only with little risk of long-term morbidity and contour deformity. The purposes of this study were to evaluate the course of a nonoperated depressed frontal sinus anterior wall fracture and to identify the cutoff value of anterior wall displacement requiring surgical correction. MATERIALS AND METHODS: A retrospective chart review of 51 nonoperated isolated frontal sinus anterior wall fractures was performed. The depth and area of each fracture were measured by computed tomographic scans. Medical records were carefully reviewed to identify the delayed complications or contour changes. RESULTS: The mean fracture depth and size were 3.9 mm and 352 mm(2), respectively. Patients who had a fracture depth of 4 mm or less did not develop late depressive contour changes of the skin. However, 7 patients who each had a fracture depth of more than 4 mm developed mild contour changes during the months of follow-up. The delayed contour change was associated with fracture depth (P < 0.01), but the fracture area was not considered as an independent factor for delayed contour deformity (P > 0.05). CONCLUSIONS: The presence of depressive contour changes on the skin is an indication for surgical correction of the frontal sinus fracture. Mildly displaced isolated frontal sinus anterior wall fractures can be observed if the fracture depression is less than 4 mm. PMID- 22777436 TI - Excision of forehead and malar lesions using endoscopic techniques. AB - The use of endoscopes via limited incisions to access areas of the forehead and cheek has allowed facial rejuvenation procedures to be performed in a way that minimizes some of the morbidities associated with more traditional approaches. The possibility of expanding the indications for these approaches arises when endoscopic, minimally invasive techniques can be applied to the excision of lesions of the upper part of the face and the midface. Such methods offer several advantages without compromising therapeutic outcome. The specific techniques used will be illustrated as they were applied in several cases. PMID- 22777437 TI - Binder syndrome. AB - Patients with chondrodysplasia punctata (CDP) usually present with Binder-type features, and often CDP is misdiagnosed as Binder syndrome. This study reviewed the management and outcome of patients with Binder syndrome and CDP in a multidisciplinary setting. METHODS: The notes and radiographs of the patients managed at the Australian Craniofacial Unit with a multidisciplinary setting since 1976 were reviewed, and data were collected on patient demographics, associated medical and surgical problems, subsequent management, and complications. RESULTS: Seventy-seven patients were treated over the 30-year period (5 patients were lost to follow-up); of the remaining 72 patients, 60 (83%) had Binder syndrome, and 12 (17%) were patients with CDP. Forty were males, and 32 were females, with an age range of 6 months to 47 years. Thirteen patients (18%) had a strong family history, and 65 patients (90%) have so far undergone surgical correction, and of those, 35 (54%) have completed their treatment, the longest follow-up time being 18 years. The mean number of surgical procedures was 2.4, and 18 patients (28%) had postoperative complications, which included partial necrosis of the maxilla, osteomyelitis of the mandible, facial nerve and inferior alveolar nerve neuropraxia, nasal bone graft exposure, and cellulitis. DISCUSSION: Because of the phenotypic characteristics shared by both Binder syndrome and CDP, it is most likely that Binder syndrome is not a syndrome, nor is it an entity, but most likely to be an "association." We would advocate that these patients should be managed in a multidisciplinary setting. PMID- 22777438 TI - Aplasia cutis congenita of the trunk associated with fetus papyraceous. AB - Aplasia cutis congenita is failure of development of all layers of the skin. This condition most commonly affects the scalp and is typically an isolated finding. In rare instances, it can affect other anatomic sites and may be associated with syndromes or other causes. We discuss an infant born with extensive aplasia cutis congenita of the trunk related to twin fetal demise (fetus papyraceous). Conservative management with moist dressings led to satisfactory healing. PMID- 22777439 TI - Two-suture fish-mouth end-to-side microvascular anastomosis with fibrin glue. AB - The most decisive step during free tissue transfers and replantation surgery may be respected as microvascular anastomosis. The conventional end-to-side anastomosis technique with simple interrupted sutures is well established and proven to be successful. On the other hand, conventional technique can be time consuming and can cause vascular thrombosis, vessel narrowing, and foreign-body reactions. Search for a more rapid and secure alternative to conventional technique is carried on. In this study, we defined a new technique for end-to side anastomosis with fish-mouth incisions and application of fibrin glue and compared our results with those we obtained with conventional end-to-side anastomosis. We evaluated end-to-side anastomosis of carotid arteries of a total number of 64 Wistar-Albino rats. In control group (n = 32), conventional anastomoses with 8 to 10 sutures were performed. In experimental group (n = 32), fish-mouth incisions were applied first on the recipient artery, followed by performing anastomosis with only 2 corner sutures and applying commercially available fibrin glue. Time taken to perform the anastomosis was significantly shorter with the experimental group (P = 0.001), whereas early and late patency and aneurysm rates were comparable to those achieved with control group. Histological evaluation did not point out any significant differences between the groups. We have defined a rapid and safe alternative technique of end-to-side anastomosis with the use of fibrin glue. This method may be an alternative especially where multiple anastomoses are required or where it is difficult to approach anastomotic line, as it is easily performed, rapid, safe, and not involving any complex equipments. PMID- 22777440 TI - Spring-assisted cranioplasty for bicoronal synostosis. AB - BACKGROUND: Numerous surgical techniques for cranial reconstruction of patients with bicoronal synostosis have been suggested. The outcome is, however, still often suboptimal. METHODS: Since 2005, we have, at the Craniofacial Unit, Sahlgrenska University Hospital, Gothenburg, used a standardized surgical technique with advancement and remodeling of the forehead combined with spring distraction of the occipital area. The aim of the current study was to evaluate this operative technique. Eighteen consecutive patients (9 boys and 9 girls) with bicoronal synostosis operated on using this technique were identified. Sixteen patients had syndromic bicoronal synostosis, and 2 had nonsyndromic bicoronal synostosis. Cephalic index was obtained from three-dimensional computed tomography scans, and photographs were analyzed for aesthetic evaluation. RESULTS: The preoperative calvarial shape was hyperbrachycephalic in all subjects. Postoperatively, the calvarial shape was, in general, much closer to the norm. The reduction in the mean cephalic index from the preoperative stage (94) to the 3-year follow-up (82) was statistically significant (P < 0.0001). The mean duration of surgery was 155 (SD, 32) minutes, with a mean perioperative bleeding of 237 (SD, 95) mL. The mean hospital stay was 6.3 (SD, 1.5) days, of which the mean intensive care unit stay was 1.6 (SD, 1.2) days. In 2 patients, one of the springs had to be reinserted because of postoperative dislocation. No other major complications were observed. CONCLUSIONS: Spring-assisted cranioplasty for bicoronal synostosis is a safe technique, is less invasive than many other cranioplasties, and results in marked improvement in the calvarial shape. PMID- 22777441 TI - Impact of septoplasty on mean platelet volume levels in patients with marked nasal septal deviation. AB - Nasal septal deviation (NSD) is a very common cause of recurrent and chronic nasal obstruction. Chronic nasal obstruction leads to increased upper respiratory tract resistance, and also upper respiratory tract resistance leads to chronic hypoxia and hypercarbic because of alveolar hypoventilation. Chronic hypoxia and hypercarbia show tendency for hypercoagulopathy.Mean platelet volume (MPV), the most commonly used measure of platelet size, is a potential marker of platelet reactivity. Large platelets that contain more dense granules are enzymatically and metabolically more active and have greater prothrombotic potential. In previous studies, increased MPV was demonstrated in hypertension, unstable angina pectoris, myocardial infarction, stroke, and obstructive sleep apnea.We aimed to determine whether MPV levels are elevated in patients with marked NSD (MNSD) compared with healthy controls. In addition, we tried to find out the effect of nasal septoplasty on MPV levels. We found that the MPV levels were significantly higher in the MNSD group than in the control healthy group, and also we found that MPV levels were significantly decreased in the MNSD group after septoplasty operation.In conclusion, in our knowledge, this is the first study investigating MPV levels in patients with MNSD. Increased platelet activation may be related to increase the cardiovascular risk in patients with MNSD. Our results suggest that MPV, a determinant of platelet activation, is elevated in patients with MNSD, and the increase in MPV levels of the cases with MNSD could be treated by septoplasty. PMID- 22777442 TI - Impact of smoking on p65 nuclear factor kappaB, p38 mitogen-activated protein kinase, and inducible nitric oxide synthase expression levels in oral mucosa. AB - OBJECTIVES: Smoking plays an important role in oral cancer development; however, the molecular carcinogenesis mechanism in oral mucosa is not well understood. The aim of this study was to examine and compare the levels of p65 nuclear factor kappaB (NF-kappaB), p38 mitogen-activated protein kinase (MAPK), and inducible nitric oxide synthase (iNOS) expressions between oral mucosa of nonsmoker and smoker volunteers. METHODS: Oral cheek mucosa was collected from 78 volunteers. Smokers were divided into 2 subgroups: light smokers (<40 pack years) and heavy smokers (>= 40 pack years). Paraffinized tissue immunochemistry was carried out for p65 NF-kappaB, p38 MAPK, and iNOS expression with specific antibodies. Results were evaluated based on diffuseness and intensity of staining. RESULTS: Group 1 composed of 40 nonsmokers: 52.5% were female and 47.5% were male, with a mean age of 46.4 years. Group 2 composed of 38 smokers (20 light smokers, 18 heavy smokers): 39.5% were female and 60.5% were male, with a mean age of 48.9 years. Total immunohistochemical staining scores of smokers were significantly higher compared with those of nonsmokers in p65 NF-kappaB, p38 MAPK, and iNOS expression (P < 0.001). The highest p65 NF-kappaB, p38 MAPK, and iNOS expression levels were detected in the oral mucosa of heavy smokers. The expression of iNOS and p65 NF-kappaB in heavy smokers was significantly higher compared to that in light smokers (P < 0.01 and P < 0.05, respectively). Although p38 MAPK expressions were higher in heavy smokers compared with light smokers, the difference was not statistically significant (P > 0.05). CONCLUSIONS: Our results show for the first time the significant increase in the expression of p65 NF kappaB and p38 MAPK in the oral mucosa of smokers. Levels of p65 NF-kappaB, p38 MAPK, and iNOS expression in the oral mucosa of smokers were related to the number of pack years. PMID- 22777443 TI - Accuracy and validity of stitching sectional cone beam computed tomographic images. AB - To determine whether three-dimensionally reconstructed images of skulls created by stitching multiple cone beam computed tomographic (CBCT) images are as accurate as single images obtained using multidetector computed tomography (MDCT), 10 skull models were scanned using an optical three-dimensional scanner, MDCT, and CBCT. Cone beam CT images at 3 different levels of the skull were manually superimposed and stitched. The reconstructed CBCT images at each level were aligned and fused using computer software and then compared to the nominal reference image obtained from the optical three-dimensional scanner by determining positional errors. The reconstructed MDCT images were also compared, and the differences in the mean errors for the 3 image types compared with the nominal reference image data were evaluated. There were no significant differences between the MDCT images and the manually merged CBCT images (Wilcoxon signed rank test, P = 0.017). In contrast, there were significant differences between the MDCT images and the software-aligned CBCT images (P = 0.005). Manual stitching of CBCT sectional images at different levels can provide accurate anatomic details of the oral and maxillofacial regions. PMID- 22777444 TI - Mantle design: a composite construct for orbital floor reconstruction. AB - We present a unique case of orbital floor and wall reconstruction after complete destruction by a self-inflicted gunshot wound. The complex comminuted fracture was repaired using a composite construct design (the mantle design) that was fixed in place using mini plates and screws. The designed composite graft was shaped exactly to fit the area of the orbital floor and maxilla to create stability and support for the globe.The orbital floor and maxilla were repaired using this special design, which was created based on the basic physical principles of mantle constructs that have been known for many years to be strong, durable, and stable. After surgery, radiologic evaluation revealed excellent placement of our construct. This particular reconstruction method may be used in patients with severe orbital bony destruction with no surrounding stable bony support elements, which are required to reconstruct the orbital floor in patients with trauma using either an autologous or a biologic implant. PMID- 22777445 TI - Diplopia and enophthalmos in blowout fractures. AB - The aim of this study was to compare the changes of diplopia and enophthalmos in patients with blowout fractures. Three hundred sixty-two patients who presented with blowout fractures between March 2006 and February 2011 were analyzed. The sequential time changes of diplopia and enophthalmos were measured in the operated group and the observed group according to (1) the duration of preoperative observation (early: within 7 days, late: 8-14 days, delayed: >15 days); (2) the defect size (minimal: <1 cm(2), small: 1.1-2.0 cm, medium: 2.1-3.0 cm(2), large: >3.0 cm(2)); and (3) the age of the patients (<20, 21-40, 41-60, >61 years).Among the 362 patients, 242 (66.9%) had an operation, and 120 (33.1%) did not. The duration of preoperative observation did not affect the postoperative diplopia or enophthalmos. There were significant differences of enophthalmos among the operated groups with a different defect size at the preoperative period (P = 0.036 [Pearson chi(2)]). There were significant differences of diplopia among the operated groups with different defect sizes at the 6 months' follow-up period (P = 0.014 [Pearson chi(2)]). The diplopia in the older age group (>60 years) was significantly greater than that of the other 3 groups at 6 months (P = 0.023) and at 12 months (P = 0.023, [Pearson chi(2)]).We think surgery should be delayed until the swelling is decreased unless the medial rectus muscle is incarcerated. We also think that the defect size is not an important factor for whether to perform surgery. We think that the reason for the greater diplopia in the older age group is that the adaptation of binocular convergence is decreased in the older age group. PMID- 22777446 TI - Influence of helmet use in facial trauma and moderate traumatic brain injury victims of motorcycle accidents. AB - OBJECTIVE: The objective of this research was to study the influence of the use of helmet in facial trauma victims of motorcycle accidents with moderate traumatic brain injury. METHODS: We retrospectively reviewed the incidence of facial injuries in helmeted and nonhelmeted victims with moderate traumatic brain injury at a referral trauma hospital. RESULTS: The sample consisted of 272 patients predominantly men (94.5%) and between 21 and 40 years old (62.9%). The majority of patients were using helmet (80.1%). The occurrence of facial fractures was most frequent for zygomatic bone (51.8%), followed by mandible (18.8%) and nasal bones (9.2%). CONCLUSIONS: Individuals in the most productive age group are most affected, which causes a great loss to financial and labor systems. It is important to take measures to alert the public regarding the severity of injuries likely to occur in motorcycle-related accidents and ways to prevent them. PMID- 22777447 TI - Scleral perforation complicating titanium mesh plaque in orbital blowout fracture. AB - A 27-year-old man who underwent a previous reconstruction surgery for left orbital blowout fracture and recent revision surgery for left cicatricial ectropion was admitted to the ophthalmology outpatient clinic with a 20-mm irregular conjunctival and scleral incision in the left eye at the 6-o'clock position. The scleral and conjunctival incisions were repaired, and during the operation, the anterior end of the titanium mesh plate was visible at the inferior orbital rim. The plastic surgery team removed the irritating end of the plate. Obvious adherence of periocular tissues onto the titanium implant and fibrovascular ingrowth through the implant were seen during this operation. The possible mechanism for the misdirection of the anterior end of the implant might be explained by iatrogenic rotation during the revision of the cicatricial ectropion. To the best of our knowledge, this is the first reported case demonstrating scleral incision caused by an orbital titanium implant. PMID- 22777448 TI - Endoscopic endonasal approach of the medial intraconal space: CT analysis of the anatomic relation between paranasal structures and orbital contents. AB - OBJECTIVE: This study aimed to investigate the anatomy of the optic nerve (ON), extraocular muscles (EOMs), and paranasal structures with regard to an endoscopic endonasal approach to the orbit using multiplanar reconstruction of computed tomographic (CT) scans. METHODS: The CT scans of 125 patients were retrospectively evaluated. The anatomic relationships between the ON, EOMs, and medial orbital floor (MOF) were measured on a coronal plane using multiplanar reconstruction of the CT scan. RESULTS: The mean distances from MOF to medial rectus (MR) and inferior rectus (IR) muscles and distance from MR to IR at the depth of the basal lamella (BL) and midportion of posterior ethmoid (PE) were measured on the coronal planes, respectively. The mean distances at the depth of PE were approximately less than 2 mm and half of those were at the depth of BL. The mean distances from ON to MOF, lamina papyracea, and EOMs at the depth of BL, PE, and sphenoid sinus anterior wall were measured, respectively. The distances from the ON to surrounding structures at the depth of PE were approximately half of those at the depth of BL and the distances from the ON to surrounding structures at the depth of sphenoid sinus anterior wall were less than 2 mm except the distance from the ON to MOF. CONCLUSIONS: The MOF and EOMs could be the most important and safe anatomic landmarks for an endoscopic approach to the orbit. These results could be used as a reference to minimize ON and EOM injury. PMID- 22777449 TI - Orbital paraganglioma: gamma knife surgery as a therapeutic option. AB - The authors report a case of orbital paraganglioma--an extremely rare orbital tumor. A 31-year-old woman presented a well-defined localized mass in the superotemporal extraconal aspect of the left orbit. Lateral orbitotomy of the left eye for excisional biopsy was performed, but the tumor could not be excised completely because of bleeding and involvement of critical structure. Histopathology and immunohistochemical analysis established the diagnosis. Gamma knife surgery was used as an alternative modality and resulted in stabilization of the tumor and preservation of her vision. We report a rare case of orbital paraganglioma, successfully managed with radiosurgery after incomplete excision. PMID- 22777450 TI - Perforating the polydioxanone sheet: avoiding intraorbital hematoma after open treatment of orbital floor fractures. AB - The surgical treatment of orbital floor fracture, a common facial injury, is not a risk-free procedure. Complications after orbital surgery can include infection, implant migration, mydriasis, epiphora, persistent diplopia, enophthalmos, infraorbital numbness, retrobulbar hemorrhage, and blindness. Blindness has been ascribed to retrobulbar hematoma in almost 50% of cases. In our experience, blood collection above the polydioxanone sheet after the treatment of orbital floor fracture can be caused by the tight adhesion of the sheet to the bony edges of the fracture. Here, we present a simple procedure to avoid this potentially dangerous complication. PMID- 22777451 TI - Positional plagiocephaly and brachycephaly: is there a correlation between subjective and objective assessment of cranial shape? AB - INTRODUCTION: During the last 2 decades, the incidence of positional plagiocephaly and brachycephaly has increased. Treatment options are conservative and can include physiotherapy and molding helmet therapy. The decision to start helmet therapy is based on patient history and subjective assessment of cranial shape by the physician and the parents. Recently, a noninvasive, objective, reliable, and valid measurement instrument became available: the plagiocephalometry (PCM). Because there are no data available comparing the result of PCM with subjective assessment of cranial shape, we performed the current study. METHODS: All consecutive children with positional plagiocephaly and brachycephaly admitted to the craniofacial outpatient clinic between October 2008 and July 2009 were included. Physician and parents assessed the cranial shape of the child, using a numeric scale from 1 to 10. In consultation with the parents, the physician decided whether helmet therapy was indicated. Plagiocephalometry was performed after visit to the physician. RESULTS: We included 75 patients in our study. There was a significant correlation between the numeric score from the physician and both the oblique diameter difference index (P < 0.001) and the cranial proportional index (P = 0.023). There was no significant correlation between the numeric score from the parents and both the oblique diameter difference index (P = 0.427) and the cranial proportional index (P = 0.155). CONCLUSIONS: There is a significant correlation between the subjective assessment of cranial shape by the physician and PCM results. Plagiocephalometry can be a useful additive tool to assess cranial shape. PMID- 22777452 TI - Mild incomplete cleft lip repair. AB - Of all the methods for repair of the unilateral cleft lip, none has gained as much popularity as the rotation advancement. Limitation of the technique leads to various modifications. It is well known that different cleft lip patients have different deformities. However, the modifications are always focused on nasal symmetry and alar base position. We found out that some microform incomplete cleft lip patients have distinctive appearance, of which the cleft located on the lower upper lip, nasal deformity is mild, and distinctive appearance presents a terrace before the peak on cleft side where it is always marked no. 9 according to rotation-advancement principle. We describe an individual technique to repair this kind of condition, which is different from Millard rotation-advancement principle. The design marking of the technique is around the cleft, and no additional incisions are located on the white lip and nasal base. PMID- 22777453 TI - A survey of multidisciplinary cleft palate and craniofacial team examination formats. AB - We surveyed 229 multidisciplinary cleft and craniofacial teams listed in the American Cleft Palate-Craniofacial Association directory regarding frequency of meetings, numbers of patients treated, sources of funding, their format of examination of children, and their satisfaction with that format. One hundred fifteen (50%) of 229 surveys were completed. Thirty-seven percent of clinics report meeting monthly; 43% of clinics report actively following up 300 or less patients; 40% of clinics report funding by third-party insurance reimbursement, and 38% by government funding; 48% of clinics report the patients moving from one examination room to another to see specialists, in another 33%, the patient stays in 1 examination room while the specialists move, and in only 20%, all specialists see a patient simultaneously. Significantly more specialists are dissatisfied with clinics where they move to examine children; significantly more families are satisfied in clinics where specialists move to examine the child or examine them simultaneously. PMID- 22777454 TI - Autologous fat transplantation in the craniofacial patient: the UCLA experience. AB - Patients with congenital craniofacial malformations present with complex challenges for reconstruction. Successful management requires individualized treatment often involving rebuilding the facial skeleton de novo, as well as correcting the overlying soft-tissue deficiencies in the final stages. At the University of California, Los Angeles (UCLA) Craniofacial Clinic, serial autologous fat transplantation performed during staged reconstruction is the preferred method.A total of 27 patients with a diagnosis of either craniofacial microsomia/Goldenhar (CM) (n = 19) or Treacher Collins syndrome (TC) (n = 8) were treated at the UCLA Craniofacial Clinic by autologous fat transfer between July 1999 and February 2009. Two-dimensional analysis was conducted on standardized preoperative and postoperative photographs to determine facial symmetry for every patient. Results was grouped based on pathology and analyzed by comparing adipocyte donor site (abdomen vs other).The mean ages at the time of first fat transfer were 17 years for the CM group and 15 years for the TC group. The average numbers of fat transfers per patient were 2.05 (CM) and 2.12 (TC). A mean of 3.74 procedures other than fat grafting was performed in each CM patient, whereas 4.38 other procedures were performed in each TC patient. In CM patients, less than 10.5 months between procedures resulted in improved symmetry. There was an average 6.63% improvement in facial symmetry in the CM group, and a 7.67% improvement in the TC group.Based on the UCLA experience, the durability of facial asymmetry and contour correction with fat transplantation is attainable in the craniofacial patient but may also require concomitant skeletal correction in the most severe cases. PMID- 22777455 TI - A novel cranioplasty technique incorporating cancellous femoral bone and recombinant bone morphogenic protein 2. AB - Large calvarial defects in the setting of chronic infection and limited autologous donor sites present challenging problems for the reconstructive surgeon. We report on a novel osteogenic implant as a potential calvarial reconstruction solution. Two patients with an extensive history of severe traumatic brain injury and multiple cranial operations desired delayed calvarial reconstruction subsequent to removal of infected acrylic and titanium implants. These patients underwent harvesting of cancellous femoral bone and bone marrow, which was placed between 2 layers of recombinant bone morphogenic protein 2 impregnated in acellular collagen sponges and an outer layer of sturdily pliable Vicryl mesh to create a moldable osteogenic implant construct. The construct was molded into the shape of the defect and secured with sutures to the skull surrounding the defect. The osteogenic implant showed evidence of bone formation and maintained coverage over the original calvarial defect at 26 months postoperatively as well as subjective satisfaction by both patients and the senior surgeon. This technically straightforward technique with acceptable functional and aesthetic outcomes may be useful to reconstructing selected calvarial defects. PMID- 22777456 TI - Forces charging the orbital floor after orbital trauma. AB - The objectives of this study were (i) to evaluate different fracture mechanisms for orbital floor fractures and (ii) to measure forces and displacement of intraorbital tissue after orbital traumata to predict the necessity of strength for reconstruction materials. Six fresh frozen human heads were used, and orbital floor defects in the right and left orbit were created by a direct impact of 3.0 J onto the globe and infraorbital rim, respectively. Orbital floor defect sizes and displacement were evaluated after a Le Fort I osteotomy. In addition, after reposition of the intraorbital tissue, forces and displacement were measured. The orbital floor defect sizes were 208.3 (SD, 33.4) mm(2) for globe impact and 221.8 (SD, 53.1) mm(2) for infraorbital impact. The intraorbital tissue displacement after the impact and before reposition was 5.6 (SD, 1.0) mm for globe impact and 2.8 (SD, 0.7) mm for infraorbital impact. After reposition, the displacement was 0.8 (SD, 0.5) mm and 1.1 (SD, 0.7) mm, respectively. The measured applied forces were 0.061 (SD, 0.014) N for globe impact and 0.066 (SD, 0.022) N for infraorbital impact. Different fracture-inductive mechanisms are not reflected by the pattern of the fracture. The forces needed after reposition are minimal (~0.07 N), which may explain the success of PDS foils [poly-(p-dioxanone)] and collagen membranes as reconstruction materials. PMID- 22777457 TI - Posttraumatic enophthalmos: injuries and outcomes. AB - BACKGROUND: The purpose of this study was to retrospectively evaluate the patients who had undergone delayed correction of posttraumatic enophthalmos. METHODS: The medical charts of 85 patients with posttraumatic enophthalmos and who underwent surgical correction at the authors' medical center were reviewed. The outcomes were analyzed in relation to various factors such as the period of delayed correction, the causes of delayed correction, the type of initial injury, the pathologic site of the orbital wall, the operative methods, and the aesthetic and functional results. RESULTS: With regard to posttraumatic enophthalmos, good aesthetic and functional results were seen in most patients. The period from the initial injury up to the delayed correction ranged from 1 to 144 months (average, 20.9 months). The most common cause of posttraumatic enophthalmos was initial inadequate repair. A zygomatico-orbital fracture was initially the most frequent facial bone fracture. The most common defect site of the orbital wall was the inferior wall. Enophthalmos was significantly improved from a preoperative average of 3.16 mm to a postoperative average of 1.29 mm. CONCLUSIONS: Better functional results were achieved for the cases of mild to moderate enophthalmos with a single defect site of the orbital wall for the patients without associated facial bone fracture. We conclude that most cases of posttraumatic enophthalmos could be prevented through careful reconstruction during the first operation. Delayed correction of posttraumatic enophthalmos could be a possible reparative procedure if sufficient release of scar tissue, accurate repositioning of the dislocated orbital bones, and proper intraorbital grafting are performed. PMID- 22777458 TI - Endoscopic endonasal management of cerebrospinal fluid rhinorrhea. AB - The authors review their 5 years' experience with endonasal endoscopic repair of the anterior skull base fistulas presenting with cerebrospinal fluid (CSF) rhinorrhea. A total of 12 patients were managed endoscopically between 2004 and 2008. Seven patients (58.3%) had nonsurgical posttraumatic CSF rhinorrhea, 2 patients (16.7%) had CSF rhinorrhea due to surgical/iatrogenic trauma, and 3 patients (25%) had spontaneous onset of CSF rhinorrhea. Radiosurgical correlation for CSF fistula identification was positive in all patients. The most common site of leak was the fovea ethmoidalis. The repair method consisted of an extradural underlay closure of a defect with fascia lata. The largest diameter of a defect to be closed was 15 mm. Immediate results were good in all patients, but later in the follow-up, CSF rhinorrhea recurred in 2 patients, and each patient had a revision 2 times. In the first revisions, transcranial approach was used, whereas in the second revisions endonasal endoscopic route was resorted. The primary closure rate was 83.3%, and the overall closure rate was 100%. The average follow up period thus far is 21 months. Endonasal endoscopic technique well known to otolaryngologists should be considered as the first choice of surgery in the repair of CSF rhinorrhea because of low morbidity and a higher closure rate. The possibility of revision with the same technique makes this approach ideal for the repair of cranionasal osteodural defects. PMID- 22777459 TI - Why does the corrective procedure of the ectropion work for repairing the entropion? AB - BACKGROUND: The accepted standard for the correction of involutional entropion has not been well established. This is our search for the reasonable answer for our dilemma. For the correction of involutional entropion, we have applied the modified Kuhnt-Szymanowski-Smith method. It brought the best result compared with other various procedures. METHODS: This report is a retrospective interventional case series of all consecutive patients with the lower-eyelid involutional entropion. They were operated exclusively by the same author with the modified Kuhnt-Szymanowski-Smith method, which was originally reported for the corrective procedure for ectropion. RESULTS: In total, 27 patients underwent surgical repair with the modified Kuhnt-Szymanowski-Smith method. There were 15 men and 12 women with a mean age of 77 years (range, 70-91 years). There was no case of recurrence following the primary procedure during 20 months of the mean follow-up period (18 36 months). CONCLUSIONS: From our experience, this is one of the procedures to be considered for involutional entropion. It is not only safe, simple, and effective but also requires short operative time. PMID- 22777460 TI - Intraoral approach for nasal tip upturning. AB - BACKGROUND: The nose is an important landmark in facial beauty, and slight modifications lead to dramatic changes. The authors describe their surgical technique to upturn the tip of the nose with an intraoral approach sectioning the fibers of muscle depressor septi. METHODS: There were 14 patients (5 male and 9 female patients) in this study. All patients complained of nasal tip ptosis. The surgical procedure was explained to the patients, and the informed consent was obtained; preoperative frontal and lateral photographs were taken. The same surgical procedure was performed in all patients. RESULTS: No complications were observed. Tip upturning, with satisfaction of the patients, was observed in all cases and was confirmed comparing preoperative and 6-month postoperative photographs. CONCLUSIONS: From the outcomes of this short case series, the surgical technique described to upturn the tip of the nose with an intraoral approach sectioning the fibers of muscle depressor septi and with the skeletization of the premaxilla is an easy, safe, and inexpensive technique that can be easily performed at the office. PMID- 22777461 TI - Clinical and radiologic features of submandibular triangle hemangioma. AB - BACKGROUND: The clinical and radiologic features of submandibular triangle hemangioma have not been systematically reported. Hemangiomas in the submandibular triangle are very rare and are often misdiagnosed as other benign cystic masses or inflammatory conditions. METHODS: We retrospectively reviewed the medical records of 5 patients who underwent surgery for submandibular triangle hemangioma between January 2006 and April 2011. RESULTS: All patients presented with fluctuating swelling with or without pain in the submandibular triangle. Computed tomographic (CT) scans showed cystic masses around the submandibular glands and calcified nodules in the lesions. Ill-defined vascular lesions and variably sized hard nodules were identified during surgery. Bleeding was controlled by early ligation of feeding vessels. The submandibular gland was removed for surgical exposure in 4 patients. Pathologic review of each specimen revealed that all were cavernous hemangiomas with thrombosis and phleboliths. Complications included 1 temporary marginal mandibular nerve paresis and 1 postoperative hematoma. No recurrence after surgery was seen during a follow-up period of 4 to 52 months. CONCLUSIONS: The possibility of submandibular triangle hemangioma should first be considered when a cystic mass around the submandibular gland and multiple calcifications are present on CT. Ligation of feeding vessels and resection of the submandibular gland may be needed to obtain surgical exposure and prevent massive bleeding. PMID- 22777462 TI - Adenotonsillectomy for the management of obstructive sleep apnea in children with congenital craniosynostosis syndromes. AB - Children with congenital craniosynostosis syndromes have a high incidence of obstructive sleep apnea (OSA). Obstructive sleep apnea has significant consequences including impaired growth, learning and behavioral problems, and cardiovascular morbidity. Adenotonsillectomy is the treatment of choice for OSA in otherwise healthy children. In children with craniosynostosis syndromes, airway abnormalities may exist at multiple levels, but midface hypoplasia leading to a reduced nasopharyngeal airway is a common significant factor; here, even normal-sized adenoids and tonsils may contribute to obstruction. To date, few studies have evaluated adenotonsillectomy for the treatment of OSA in children with syndromic craniosynostosis. In this study, we assessed the effectiveness of adenotonsillectomy by comparing preoperative and postoperative sleep study data. We also evaluated whether adenotonsillectomy could obviate the need for tracheostomy in these patients. Five children with syndromic craniosynostosis and moderate to severe OSA underwent adenotonsillectomy at a mean age of 4.0 years (range, 1.7-5.1 y). Two patients (40%) showed improvement in OSA severity grade and 1 patient had complete resolution. Three children (60%) avoided tracheostomy and had no further airway surgery. Our results provide evidence to support the use of adenotonsillectomy in treating OSA in children with syndromic craniosynostosis. Adenotonsillectomy should be considered before tracheostomy or more major surgery in this patient group. PMID- 22777463 TI - New treatment for cystic lymphangiomas of the face and neck: cyst wall rupture and cyst aspiration combined with sclerotherapy. AB - Cystic lymphangioma is a congenital malformation occurring most frequently in the necks of infants and young children. It is histologically benign, but the lesion can extend deep into the tissue. Thus, surgical treatment is often difficult. In recent years, OK-432 sclerotherapy has become the first-line therapy for cystic lymphangioma, and many reports have discussed its effectiveness. However, it is difficult to achieve a complete response to OK-432 in polycystic cases and cases with small cystic areas, and it is sometimes ineffective. In the current study, we performed a new combination therapy on 5 cases of cystic lymphangioma of the face and neck. In this combination therapy, we ruptured the cyst wall of lymphangioma using a liposuction device and subsequently used OK-432 to induce inflammation and to cause adhesion of cyst walls. The combination therapy produced very good results. None of the patients had any major complication or recurrence. All patients had lymphangiomas that markedly reduced in size. This new method can be performed regardless of the cyst type of lymphangioma and is thought to be a useful therapy. PMID- 22777464 TI - Complications of pediatric facial fractures. AB - Pediatric facial fractures account for only 5% of all facial fractures, with even a much lower incidence in children younger than 5 years (1%-1.5%). The evolution of principles in the management of pediatric facial fractures and the differences in management between adult and pediatric patients have been well documented in the literature. Pediatric facial fracture management presents unique challenges because it might affect growth in the area specific to the trauma segment. Children are, in several ways, at a regenerative advantage: greater osteogenic potential, faster healing rate, primary dentition that is thereby temporary, and the capacity for significant dental compensation. Perhaps because of this, complications such as infection, malunion, nonunion, and postinjury malocclusion are relatively rare compared with the adult population. In this article, we will focus on different approaches to complications that arise after pediatric fracture management. PMID- 22777465 TI - Technique of making holes and passing wires in subcondylar fractures. AB - The aim of this study was to describe the precise method for making holes and passing wires in a subcondylar fracture. The subcondylar fracture sites were accessed by making a submandibular incision. At the preauricular area, an 18 gauge 1.5 needle (inner diameter, 1.05 mm) was put from the skin to the distal end of the proximal fragment. Then a no. 1 Kirschner wire (diameter, 0.9 mm) was then inserted through the needle; it passed through the proximal fragment and was retrieved. Thus, a small hole approximately 1 mm was made on the proximal segment. A 27-gauge suture wire (diameter, 0.38 mm) was passed through the needle and the hole on the proximal segment. The tip of the wire was pulled using a loop made of a paper clip at the medial side of the proximal fragment. Another hole was made at the distal (major) segment with the same method. The tip of the wire, which traversed through the proximal fragment, was put into the hole on the distal segment, making a figure-of-8 pattern. The wire was tightened, and the fracture site was immobilized.We believe that this method of making holes and passing wires using a needle and K-wire might be a simple and quick alternative technique for treating subcondylar fractures. PMID- 22777466 TI - Spatulated anastomosis with continuous suture in microreconstructive surgery. AB - In a well-proven criterion standard technique commonly used in cardiovascular surgery for anastomosis, proximal and distal vessels are spatulated to increase the anastomotic surface and improve congruency between the 2 vessels. Anastomosis is performed with continuous suture of the 2 bisected extremities.A review of the current literature has confirmed that our preliminary results were similar to those achieved by surgeons using the simple interrupted suture technique for microsurgical anastomosis.Patency is highly satisfactory with this technique for anastomosis. Moreover, it is a reliable technique requiring shorter total operative time. Hemostasis is easy to control and can be used with vessel diameters as small as 1 mm. For all these reasons, this technique already commonly used in vascular surgery for anastomosis could be interesting in microsurgery as well. PMID- 22777467 TI - The "YouTube" method of correcting pixie ear and poor alar base inset. AB - It is well established that raw edges of the skin have a natural tendency to tube on themselves. Although this often presents a challenge for plastic surgeons, the following article demonstrates how the plastic surgeon can capitalize on this phenomenon to successfully recreate the natural appearance of curved anatomic elements. Two areas that are particularly susceptible to appearing "unnatural" after surgery are the earlobe and alar base. Herein, we present the concept of "autotubing" to recreate the natural curvature of these anatomic regions. PMID- 22777468 TI - Effects of lidocaine plus epinephrine and prilocaine on autologous fat graft survival. AB - Although fat grafting is frequently used in plastic surgery practice, debate about the viability of the graft still persists owing to its questionable long term success. The ultimate aim is to obtain long-term graft viability. Vascularization of the graft is essential for this purpose. The effects of 2 different local anesthetic preparations frequently used during harvesting of fat grafts on long-term graft survival were compared with angiogenesis and volumetric measurements. Twenty-four male Wistar rats were divided into 3 groups. The inguinal region was selected as the fat graft donor site. The first group was injected with isotonic saline, the second was injected with lidocaine plus epinephrine, and the third was injected with prilocaine. Fat grafts were implanted into the dorsal regions of rats, and volumetric measurements were performed initially and on days 30 and 180 at which microvascular angiogenesis were also analyzed. Microvascular angiogenesis was assessed both with the reverse transcription-polymerase chain reaction and immunohistochemistry through determination of vessels stained with factor VIII. No significant difference was obtained between the 3 groups in graft volume or microvascular angiogenesis at any stage of the study. Results from this experimental study indicate that there is no negative effect of lidocaine plus epinephrine or prilocaine on microangiogenesis and the survival of fat grafts. PMID- 22777469 TI - Buccal reconstruction with the mouth floor mucosal flap. AB - A mouth floor mucosal flap was developed to reconstruct medium-sized intraoral buccal defects, too large for primary closure if major functional and aesthetic impairment is to be avoided. Although free flaps, perforator flaps, or even skin grafts can be designed for buccal reconstruction, they may not provide good mucosal sensitivity, motility, volume, and texture to replace lost structures with similar tissue. Moreover, secondary morbidity can be avoided with this adjacent flap.In our study, 8 flap reconstruction procedures were performed from March 2009 to July 2011: 4 cases of leukoderma, 2 cases of buccal cancer (T1 N0 M0), and 2 cases of papillary epithelioma. The largest size amount to 5.3 * 3.8 cm (length * width), with a mean of 4.3 * 3.4 cm. Compared with free flaps (forearm arm flap for example) for buccal reconstruction, application of the mouth floor flap has its indications. First, to secure the motility of tongue and function of mouth opening, the upper bound of the defects was below the occlusion line. Generally, the width between top and bottom was less than 4 cm. Second, at least a partial buccinator muscle can be preserved after lesion resection and then facial collapse can be avoided. Third, patients had molar absence or relevant teeth had to be extracted during surgery.All patients recovered from intraoral surgeries with good objective and subjective speech and swallowing and aesthetics and without injury to the lingual nerve, the submandibular gland duct, and the sublingual gland. Results indicate that the mouth floor mucosal flap is reliable and technically easy for reconstructing medium-sized intraoral buccal defects, with good function and aesthetics with little secondary morbidity. PMID- 22777470 TI - Indications and limitations of endoscopic endonasal orbitotomy for orbital lesion. AB - BACKGROUND: Endoscopic endonasal surgical techniques have developed tremendously in the last 20 years. Endoscopic techniques have been applied to the treatment of cranial base lesions, pituitary tumors, orbital lesions, pterygopalatine fossa lesions, infratemporal fossa lesions, posterior cranial fossa lesions, and clival lesions. In some reports, endoscopic endonasal transparanasal orbitotomies have been indicated for lesions localized to the medial and inferomedial parts of the orbit. The aim of this article was to present the technique of endoscopic endonasal orbitotomy (EEO) for orbital extraperiosteal and intraperiosteal lesions, as well as its indications and limitations. METHODS: We present cases of 4 patients who underwent EEO for typical extraperiosteal and intraperiosteal orbital lesions. We examined the indications and limitations in each case. RESULTS: All 4 orbital lesions were completely removed by EEO with no major complications. CONCLUSIONS: The EEO procedure, which does not require a skin incision, is a minimally invasive surgery used for treating orbital retrobulbar lesions. It leads to excellent cosmetic results with little bleeding. In the future, we need to determine its operative indications, safety, and dangers. It is necessary for us to further improve this surgical technique to allow for the generalization of the procedure. PMID- 22777471 TI - Standardized anthropometric evaluation of ectropion repair results. AB - BACKGROUND: Before undergoing ectropion repair, most patients are concerned not only about the functional result, but also about their postoperative aesthetic appearance. Furthermore, there is an ongoing discussion in the literature about the influence of various surgical techniques on eyelid function and morphology. We present a photograph-assisted evaluation for preoperative planning, intraoperative estimation, and postoperative evaluation of ectropion surgery based on anthropometric measurements and clinical data. PATIENTS AND METHODS: From January 2008 to December 2010, 36 ectropion patients underwent a lateral tarsorrhaphy or fascial sling repair. An analysis of standardized preoperative and postoperative photographs included measurements of intercanthal width, biocular width, eye fissure width, eye fissure height, lid sulcus height, upper lid height, upper iris coverage, lower iris coverage, position of cornea to palpebra inferior, canthal tilt, scleral show, and ectropion. RESULTS: Eye fissure index (P < 0.01) and lower iris coverage (P < 0.01) were statistically significantly influenced by surgery and time. The rates of scleral show (P < 0.01) and ectropion (P < 0.01) were significantly influenced, too. The 2 applied surgical techniques, lateral tarsorrhaphy and fascial sling repair, presented no significantly different effect in the preoperative to postoperative measurements. CONCLUSIONS: In all analyzed patients, the performed measurements were reproducible and reliable. The methods described may help to estimate the necessary extent of correction in ectropion repair surgery. Furthermore, intraoperatively performed measurements could be compared with the postoperative results. PMID- 22777472 TI - Avulsion of globe following maxillofacial trauma. AB - Avulsion of the eye globe is a rare condition that is unexpected in maxillofacial trauma and results from severe trauma to the orbit and face. A search of the literature reveals very few reported cases. The present article reports a case of this singular, challenging condition and comments on several other related causes, pathophysiology mechanisms, risks, complications, and management. PMID- 22777473 TI - Cone-beam computed tomography: accuracy of three-dimensional cephalometry analysis and influence of patient scanning position. AB - The aim of this research was to analyze the influence of the position of the skull during cone-beam computed tomography (CBCT) scan and if the three dimensional cephalometric measurements are influenced by skull orientation during CBCT scan.The study consisted of 5 CBCT scanning (KODAK 9500 Cone Beam 3D System unit) in 5 different positions of a dry skull. The data were imported in SIMPLANT OMS Software version 13.0. Fifteen three-dimensional cephalometric measurements were calculated; moreover, the mean, the SD, the maximum/minimum Delta, and the maximum/minimum Delta percentage were calculated. The statistical analysis was performed by an independent-samples t-test to evaluate differences between the 5 scans.No difference was found in all the three-dimensional analysis. Twelve of 15 measurements have a Delta greater than 1.5, and 7 of 15 measurements have a Delta greater than 2. Nine of 15 have a Delta percentage greater than 5%. The preliminary results suggest that the three-dimensional cephalometric analysis is influenced by patient scanning position. PMID- 22777474 TI - Aggressive inflammatory pseudotumor of the mandible. AB - Inflammatory pseudotumor (IP) is a nongranulomatous inflammatory process with no apparent local or systemic cause. The distinction between IP and malignant tumor is of great clinical importance. The incidence of IP in the head and neck region is very low. Inflammatory pseudotumor is a distinct pathological entity rarely found in the jaw bones. A rare case of aggressive IP of the mandible is presented along with its clinicopathologic features and surgical management. PMID- 22777475 TI - Isolated inverting papilloma of the sphenoid sinus: clinical presentations, imaging manifestations, and therapeutic strategies. AB - BACKGROUND: Isolated inverting papilloma (IP) of the sphenoid sinus is rare, with about 50 patients reported in the English-language literature. With its rarity, scientists have paid less attention to the clinical and radiographic characteristics of isolated IPs arising from the sphenoid sinus. METHODS: We describe the clinical presentation, imaging manifestations, and surgical methods of isolated IPs from the sphenoid sinus in 3 patients and review the English language literature from 1970 to 2011. RESULTS: In total, 59 cases of isolated sphenoid sinus IPs (including our cases) have been reported, 40 patients with computed tomography or magnetic resonance imaging details. The most common presentation is headache. Lesions were found in the sphenoethmoidal recess in 26 cases. In 8 patients who underwent enhanced magnetic resonance imaging, the tumor was obviously intensified. We found 26 patients with bony destruction, and 8 lesions revealed the correct tumor origin. CONCLUSIONS: A polyp-like mass in the sphenoethmoidal recess strongly implied the diagnosis of an IP in the sphenoid sinus. Bony destruction on computed tomography is a common characteristic of this disease and had a close relationship with the original tumor site in our study. Malignant transformation of IPs in the sphenoid sinus is much scarcer. PMID- 22777476 TI - Primary orbital fracture repair: development and validation of tools for morphologic and functional analysis. AB - The purpose of this study was to develop and validate a technique for objective quantitative evaluation of outcomes of orbital reconstruction. Facial three dimensional images were captured using a Vectra three-dimensional camera. Morphometric analysis was based on interactive anthropometric identification. The analysis was applied to a population of healthy adults (n = 13) and a population of patients following primary repair of unilateral orbital fractures (n = 13). Morphologic results following reconstruction were evaluated by identifying residual asymmetries. All subjects further completed the Derriford Appearance Questionnaire and the Orbital Appearance and Function Questionnaire.Normative reference values for periorbital asymmetry were determined in a reference population. The mean asymmetry was less than 1.6 mm for each measured morphologic feature. In the trauma population, primary orbital reconstruction effectively restored normal periorbital symmetry in 16 of 20 measured parameters. The fracture population showed no significant differences in the degree of asymmetry in globe projection, lower eyelid position, or ciliary margin length.The overall DAS59 scores were significantly higher in the fracture population (P = 0.04). This was due to significantly higher physical distress and dysfunction scores (P = 0.02), as well as a trend toward higher general and social self-consciousness scores (P = 0.06). No significant difference in facial self-consciousness was noted (P = 0.21). Thus, although primary orbital reconstruction was effective in restoring periorbital morphology, patients still experienced a higher level of physical distress and dysfunction than their nontraumatized counterparts. This was in accordance with patient self-report, which indicated that a greater percentage of patients were significantly bothered by functional outcomes postoperatively as opposed to appearance. PMID- 22777477 TI - Correlation of types of orbital fracture and occurrence of enophthalmos. AB - We sought to investigate the correlation between type of orbital fracture and occurrence of traumatic enophthalmos. The 119 patients with orbital fractures were divided into the enophthalmos group (71 cases) and the nonenophthalmos group (48 cases). The 2 groups were compared by location and type of orbital fracture based on observation of computed tomography scans. We found the incidence of medial wall fractures significantly higher in the enophthalmos group (76.06%) than in the nonenophthalmos group (22.92%, chi(2) = 32.63, P < 0.05). The incidence of combined medial-inferior wall fractures was also significantly higher in the enophthalmos group (52.93%) than in the nonenophthalmos group (12.5%, chi(2) = 23.21, P < 0.05). However, the incidence of lateral-inferior wall fractures was significantly lower in the enophthalmos group (36.62%) than in the other group (58.33%, chi(2) = 4.11, P < 0.05). In most cases of lateral inferior orbital wall fracture in the enophthalmos group, the zygomatic complex was displaced toward the lateral-posterior direction. The combined medial inferior wall fracture is likely the primary type of multiple wall fracture leading to traumatic enophthalmos. Enophthalmos caused by a combined lateral inferior fracture may be correlated with lateral-posterior displacement of the zygomatic complex. PMID- 22777478 TI - Secondary reconstruction of severe contracted eye socket using modified ocular conformer-drainage tube system. AB - Eye socket reconstruction has been previously reported; however, few reports address reconstruction in cases of socket contracture after graft failure. This is a retrospective observational case study of 42 patients who had previously undergone eye socket reconstruction after posttraumatic enucleation owing to severe thermal or chemical injury, and each of whom presented with a severe contracted eye socket. Patients underwent free skin grafts and the placement of a modified ocular conformer-drainage tube system. Eye sockets of adequate size were created in the 42 patients. Three patients presented with gradual extrusion of the eye prosthesis due to recurrent contraction of the inferior fornix after treatment. These patients agreed to further operative procedures 6 months after secondary reconstruction surgery, which resulted in mild upward tilting of the eye prosthesis without extrusion. The prosthetic eyes fit well in all of the secondary reconstructed sockets using this technique. Our studies suggest that the modified ocular conformer-drainage tube system can efficiently control infection after secondary reconstruction of the posttraumatic contracted socket and may result in less shrinkage of skin grafts. PMID- 22777479 TI - Human eye via reality and art. AB - This article related to a man's head is a follow-up to previous articles published in this journal entitled "Numerical Survey of the Different Shapes of the Human Nose," "Ear Concha Shapes," and "Quantitative Survey of Human's Leg Toes Shape." The author believes that the different artistic display of the eye gives a better understanding and concept of our most important organ. PMID- 22777480 TI - Apert syndrome: quality of life and challenges of a management protocol in Brazil. AB - Apert syndrome is a complex craniofacial deformity with a broad clinical spectrum that mainly affects the craniofacial skeleton, lower and upper limbs. The quality of life for patients born with Apert syndrome may be strongly affected by the limitations that this syndrome imposes. The aims of this study were to describe the quality of life of patients born with Apert syndrome and the challenges of managing an Apert protocol in Brazil. The quality of life of 8 Apert patients who adhered to our management protocol was assessed using the Portuguese version of WHOQOL-100 (World Health Organization Quality of Life instrument). The answers were submitted to SPSS (Statistic Package for Social Science), and results were expressed in 25 facets and 6 domains (physical, psychological, social relations, level of independence, environment, and spirituality). Patients and families signed an informed consent, and the study was previously approved by our institutional review board. The cohort of patients scored 60 in 22 of 25 facets, with no grade less than 50. The facet of positive feelings note was 76.79; self esteem and body image scored, respectively, 75.00 and 85.71. When the facets were grouped into domains, they had a high overall score. The cohort of Apert patients presented a satisfactory quality of life. This cohort of Apert patients acquired the necessary repertoire to manage the aversive daily situations of their lives. PMID- 22777481 TI - Solitary epithelioid histiocytoma (reticulohistiocytoma) of the glans penis. AB - Solitary epithelioid histiocytoma (previously called reticulohistiocytoma) is a rare benign dermal histiocytic proliferation characterized by the presence of large, eosinophilic histiocytes with 'glassy' cytoplasm. This entity assumes importance because of its close histologic resemblance to several benign as well as malignant cutaneous lesions. Involvement of the penis is extremely rare, and to our knowledge, only one case has been previously described in the literature. We report a case of solitary epithelioid histiocytoma in a 34-year-old man who presented with a nodule in the glans penis. Microscopy showed proliferation of large epithelioid histiocytes with abundant eosinophilic cytoplasm, which expressed CD68, CD163 and vimentin. This case highlights the significance of recognizing this unusual lesion and differentiating it from its histologic mimics. PMID- 22777482 TI - [The bicompartmental knee joint prosthesis Journey Deuce: failure analysis and optimization strategies]. AB - BACKGROUND: The Journey Deuce bicompartmental knee system is intended for patients with medial and patellofemoral arthritis of the knee and is aimed at diversifying the treatment options for knee arthritis. The prosthesis consists of a combined femoral shield with a medial condylar resurfacing component and a fixed bearing unicondylar tibial knee prosthesis. The advantages of the Journey Deuce system compared to total knee arthroplasty (TKA) are the bone sparing and cruciate retaining implantation. Outcome studies and investigation with respect to success and revision rates are rare. Thus the aim of this study was to investigate the early functional outcome as well as the revision and complication rates in patients with a Journey Deuce prosthesis within the first 2 years. METHODS: In this study 43 patients (25 female/18 male, average age 62.4 +/- 8 years and mean body mass index27.3 +/- 4.5 kg/m(2)) underwent bicompartmental knee arthroplasty using the Journey Deuce prosthesis between March 2008 and March 2009. Inclusion criteria were clinically and radiographically confirmed patellofemoral arthritis, ligament stability and flexion > 90 degrees . Exclusion criteria were extension deficits > 5 degrees , axis deviation > 10 degrees and patellofemoral malalignment. Patients were followed up for 6, 12 and 24 months postoperatively. Follow-up consisted of clinical and radiographical examination as well as a survey of the Knee Society score (KSS), a pain score (visual analog scale VAS, range 0-10) and a satisfaction score. RESULTS: Of the patients 35 (82%) patients reached the 2-year follow-up and of these 35 patients 26 (75%) had a good to very good satisfaction, a mean KSS of 93 (range 65-100) and a minimal pain score of 1.2 (range 0-4). After 12 months all patients had a knee flexion of more than 90 degrees (mean 116 degrees , range 95 degrees -140 degrees ). Loosening was not detected but 8 (18%) patients had to undergo revision within the first year due to persistent knee pain and instability. CONCLUSIONS: Under clear indications and exact anatomical positioning the Journey Deuce prosthesis enables a good functional outcome; however, a high revision rate occurred in this study caused by technical complexity and insufficient variety of implant sizes which led to malalignment and instability. Additional positional guidance and a higher variability in implant sizes are required to enable an adequate treatment with anatomically correct positioning. The Journey Deuce prosthesis would then be a reasonable diversification of the endoprosthesis spectrum in knee arthroplasty and would allow a more individual and selective treatment of patients with knee arthritis. PMID- 22777483 TI - MyD88 signaling pathway is involved in renal fibrosis by favoring a TH2 immune response and activating alternative M2 macrophages. AB - Inflammation contributes to the pathogenesis of chronic kidney disease (CKD). Molecules released by the inflamed injured tissue can activate toll-like receptors (TLRs), thereby modulating macrophage and CD4(+) T-cell activity. We propose that in renal fibrogenesis, M2 macrophages are recruited and activated in a T helper subset 2 cell (T(H)2)-prone inflammatory milieu in a MyD88-dependent manner. Mice submitted to unilateral ureteral ligation (UUO) demonstrated an increase in macrophage infiltration with collagen deposition after 7 d. Conversely, TLR2, TLR4 and MyD88 knockout (KO) mice had an improved renal function together with diminished T(H)2 cytokine production and decreased fibrosis formation. Moreover, TLR2, TLR4 and MyD88 KO animals exhibited less M2 macrophage infiltration, namely interleukin (IL)-10(+) and CD206(+) CD11b(high) cells, at 7 d after surgery. We evaluated the role of a T(H)2 cytokine in this context, and observed that the absence of IL-4 was associated with better renal function, decreased IL-13 and TGF-beta levels, reduced arginase activity and a decrease in fibrosis formation when compared with IL-12 KO and wild-type (WT) animals. Indeed, the better renal outcomes and the decreased fibrosis formation were restricted to the deficiency of IL-4 in the hematopoietic compartment. Finally, macrophage depletion, rather than the absence of T cells, led to reduced lesions of the glomerular filtration barrier and decreased collagen deposition. These results provide evidence that future therapeutic strategies against renal fibrosis should be accompanied by the modulation of the M1:M2 and T(H)1:T(H)2 balance, as T(H)2 and M2 cells are predictive of fibrosis toward mechanisms that are sensed by innate immune response and triggered in a MyD88-dependent pathway. PMID- 22777484 TI - Celiac injury due to arcuate ligament: an endovascular approach. AB - Celiac trunk injures are rare events, with high mortality rates and difficult management. Endovascular treatment may be considered to avoid bleeding. We report a case of severe bleeding in a 37-year-old man resulting from celiac trunk stretching after a motorcycle crash. Because direct celiac trunk catheterization was not possible, a retrograde catheterization of the common hepatic artery was performed via the superior mesenteric artery. Two vascular plugs (type IV) were released, and the exclusion of the celiac trunk origin was completed with the deployment of an aortic cuff. The patient's clinical condition immediately improved, and after 6 months' follow-up, imaging confirmed the complete exclusion of the celiac trunk. PMID- 22777486 TI - "My mother was 67. . . ". PMID- 22777487 TI - Long-term evaluation of phrenic nerve pacing for respiratory failure due to high cervical spinal cord injury. AB - OBJECTIVES: Phrenic nerve pacing is a method of respiratory support that can replace mechanical ventilation in high-level cervical spinal cord injury patients with diaphragmatic paralysis. Our objective was to evaluate survival and long term quality of life in patients with external respiratory support by PNP vs volumetric respirator in patients with severe respiratory insufficiency due to a high-level spinal cord injury. DESIGN: This is a retrospective review study of a prospectively collected database for evaluate the survival and a questionnaire for quality of life has been collected face-to-face or by telephone at present. PATIENTS: Cervical SCI patients with permanent respiratory support (PNP or MV). METHODS: Long-term evaluation of a cohort of PNP-supported patients. We performed a comparison between these patients and volumetric respirator-supported patients. For survival analysis, we used the Kaplan-Meier method and Cox proportional hazards model. The health-related quality of life was assessed with SF-36 questionnaire, a general HRQL evaluation. RESULTS: One hundred twenty six patients on permanent respiratory support were evaluated during the study period. Of these, 38 were on PNP and 88 were mechanically ventilated. Paced patients were younger and had a longer survival, but in a multivariate analysis adjusted for age using a multiple logistic correlation we found that length of survival was greater for PNP patients. In terms of HRQL, the PNP-supported patients showed better results in terms of social functioning. CONCLUSIONS: PNP is a stable and effective method of long-term respiratory support in this type of patients (SCI patients dependent on external respiratory support). In these patients it improves the length of survival and some social issues by quality of life when compared with patients under MV. PMID- 22777488 TI - Systematic review of the methodological quality and outcome measures utilized in exercise interventions for adults with spinal cord injury. AB - STUDY DESIGN: Systematic literature review. OBJECTIVES: The primary aims of this study were to evaluate the methodological quality of exercise intervention studies in adults with spinal cord injuries (SCIs); and to classify the reported outcome measures according to the International Classification of Functioning, Disability and Health (ICF). METHODS: Electronic searches of PubMed, CINAHL, SPORTDiscus, PsychINFO, Scopus and the Cochrane Center Register of Controlled Trials from 2001 to 2011 were performed. Selected studies were evaluated for methodological quality using the Downs and Black checklist. Outcome measures were extracted and linked to categories of the ICF using standardized linking rules. RESULTS: Two-hundred forty abstracts were retrieved, 57 studies met eligibility criteria. The mean methodological quality score was 14.7 +/- 3.2 out of 28 on the Downs and Black checklist. Three-hundred seventy four outcome measures were extracted with 333 concepts linked to 35 second-level ICF categories across the four components. CONCLUSION: Studies of exercise interventions for adults with SCI included in this review are generally low in methodological quality, primarily reporting outcomes related to the Body Functions and Body Structures components of the ICF. It is recommended that studies employ more vigorous methodological designs to reduce bias and confounding, and include outcome measures targeting more categories in the Activities and Participation component so as to reflect the potential benefits of exercise on health and functioning in this population. PMID- 22777489 TI - Time of physical exercise practice after injury in cervical spinal cord-injured men is related to the increase in insulin sensitivity. AB - OBJECTIVES: Physical exercise has an important role in reducing body fat, risk of chronic disease and systemic inflammation. The aim of this study was to determine serum leptin and insulin concentrations and their relationship to the time of physical exercise after injury in men with cervical spinal cord injury (c-SCI). METHODS: c-SCI subjects with lesion level in C5-C7 (n=25) were divided into two groups: physically active (PA, n=13; those who practiced physical exercise for at least 3 months, three times per week or more, for a total minimum of 150 min of physical activity per week) and non-physically active (N-PA, n=9). Body composition was assessed by dual energy X-ray absorptiometry. Blood samples were obtained 12 h after an overnight fast to measure insulin and leptin in serum, and glucose and C-reactive protein (CRP) in plasma, by validated methods. RESULTS: Comparing the PA and N-PA group, the first presented lower: total body mass ( 13%), body mass index (-16%), fat mass (kg -39%, FM% -30%), CRP (-23%), serum insulin (-61%), homeostasis model assessment (HOMA, -35%) and serum leptin (-62%; P<0.05). Both serum insulin (r=-0.561; P<0.05) and HOMA (r=-0.591; P<005) were inversely proportional to the time of practice of physical activity after injury. CONCLUSION: Our results suggest that exercise was able to reduce fat mass and increase insulin sensitivity, decreasing plasma levels of risk factors in c-SCI subjects. PMID- 22777490 TI - Factors associated with the development of pressure ulcers after spinal cord injury. AB - STUDY DESIGN: Cross-sectional observational study. OBJECTIVES: To examine variables associated with the development of pressure ulcers in subjects with spinal cord injury (SCI). SETTING: SCI patients under coverage of the State Welfare Organization of Iran. METHODS: Mobile rehabilitation teams gathered data from 20 of the 30 provinces in Iran. There were 8104 SCI patients registered in the database; 7489 patients were included in the analysis. The prevalence of PU in patients aged <10 years was lower than those aged >10; therefore, we used different logistic models for these groups. Likewise, separate models were created for patients who had experienced SCI during the past year versus patients injured >1 year before the evaluation. RESULTS: PU was present in 34.6% of the patients. The variables associated with PU in patients aged <10 years were female gender and the time passed since SCI. In patients aged >11 years, male gender, the time passed since SCI, lower level of education, lack of an intimate partner, quadriplegia and older age presented a significant association with PU. Patients for whom <1 year has passed since SCI, male gender, quadriplegia and older age were associated with PU. And patients for whom >1 year had passed since SCI, male gender, quadriplegia, older age, lower level of education and lack of an intimate partner were associated with PU. CONCLUSION: SCI patients are a heterogeneous group and the risk factors associated with PU may vary in specific subgroups. Different models are needed to describe PU in SCI patients depending on the patient's age and the time passed since SCI. PMID- 22777491 TI - Traumatic spinal cord injury in Saudi Arabia: an epidemiological estimate from Riyadh. AB - STUDY DESIGN: Retrospective study. OBJECTIVES: To review traumatic spinal cord injury rates and epidemiology at the Riyadh Military Hospital in Saudi Arabia and to hypothesise strategies for a more integrated approach to injury prevention in Saudi Arabia. SETTING: RMH, Rehabilitation Division. METHODS: A review was conducted of all patients with TSCI aged >=14 years admitted to RMH from January 2003 to December 2008. Descriptive analysis was performed for age, gender, cause of TSCI, completeness and neurological level of the injury. RESULTS: In all, 307 TSCI patients were admitted during this period: 88% were male, and their mean age was 29.5 years old were the main cause of TSCI (85%). CONCLUSIONS: TSCI in Saudi Arabia affects mainly the male population. The rate of RTAs caused by four wheeled vehicles is the highest globally reported RTA statistic. Primary prevention strategies specific to the region should be developed to decrease the number of car accidents. The higher-than-expected rate of complete injuries may reflect practices in acute management and transport, and suggests that a review of the acute and integrated management of TSCI may also be necessary. PMID- 22777492 TI - Intraoperative facial electromyography and brainstem auditory evoked potential findings in microvascular decompression for hemifacial spasm: correlation with postoperative delayed facial palsy. AB - BACKGROUND: Delayed facial palsy (DFP) after microvascular decompression (MVD) in patients with hemifacial spasm (HFS) is not uncommon, but the cause remains unknown. OBJECTIVES: To assess whether intraoperative electromyography (EMG) and brainstem auditory evoked potential (BAEP) can predict DFP after MVD. METHODS: Between September 2009 and February 2011 we examined 86 patients, 9 of whom (10.4%) developed DFP after MVD on the same side. All patients underwent MVD and were followed-up for a median period of 13 months (range 6-22). We retrospectively examined intraoperative facial EMG and BAEP findings using our MVD patients' registry. We excluded secondary HFS and immediate postoperative facial palsy after MVD in this study. We assessed the prevalence and clinical characteristics of DFP and compared EMG and BAEP findings between DFP and non-DFP groups. RESULTS: All patients recovered completely, with a mean time to recovery of 37.8 days (range 22-57). There were no significant differences between DFP and non-DFP patients in terms of the amplitude and latency of intraoperative EMG and BAEP. CONCLUSION: The usefulness of intraoperative facial EMG and BAEP is limited and cannot predict DFP after MVD for HFS. We speculate that DFP after MVD is not associated with permanent nerve damage according to the EMG findings. PMID- 22777494 TI - Relationship Among CFH and ARMS2 Genotypes, Macular Pigment Optical Density, and Neuroretinal Function in Persons Without Age-Related Macular Degeneration. AB - OBJECTIVES To determine whether there is a difference in neuroretinal function and in macular pigment optical density between persons with high- and low-risk gene variants for age-related macular degeneration (AMD) and no ophthalmoscopic signs of AMD, and to compare the results on neuroretinal function to patients with manifest early AMD. METHODS Neuroretinal function was assessed with the multifocal electroretinogram for 32 participants (22 healthy persons with no AMD and 10 patients with early AMD). The 22 healthy participants with no AMD had either high- or low-risk genotypes for CFH (rs380390) and/or ARMS2 (rs10490924). Trough-to-peak response densities and peak-implicit times were analyzed in 5 concentric rings. Macular pigment optical density was assessed by use of customized heterochromatic flicker photometry. RESULTS Trough-to-peak response densities for concentric rings 1 to 3 were, on average, significantly greater in participants with high-risk genotypes than in participants with low-risk genotypes and in persons with early AMD after correction for age and smoking (P < .05). The group peak-implicit times for ring 1 were, on average, delayed in the patients with early AMD compared with the participants with high- or low-risk genotypes, although these differences were not significant. There was no significant correlation between genotypes and macular pigment optical density. CONCLUSIONS Increased neuroretinal activity in persons who carry high-risk AMD genotypes may be due to genetically determined subclinical inflammatory and/or histological changes in the retina. Neuroretinal function in healthy persons genetically susceptible to AMD may be a useful additional early biomarker (in combination with genetics) of AMD before there is a clinical manifestation. PMID- 22777493 TI - Differential expression of SLC9A9 and interacting molecules in the hippocampus of rat models for attention deficit/hyperactivity disorder. AB - SLC9A9 [solute carrier family 9, member 9, also known as Na(+)/H(+) exchanger member 9 (NHE9)], has been implicated in human attention deficit/hyperactivity disorder (ADHD), autism, and rat studies of hyperactivity and inattentiveness. SLC9A9 is a membrane protein that regulates the luminal pH of the recycling endosome. We recently reported the interactions of SLC9A9 with two molecules: calcineurin homologous protein (CHP) and receptor for activated C-kinase 1 (RACK1). We also reported two novel SLC9A9 mutations and abnormal gene expression profiles in the brains of an inattentive type rat model of ADHD (WKY/NCrl rat). In this study, we further examined the expression and relationship of SLC9A9 and 9 additional genes (CHP, RACK1, CaM, PPP3R1, PPP1R10, PKCm, CaMKI, NR2B, PLCb1) that may directly or indirectly interact with SLC9A9 in the hippocampus of the WKY/NCrl rat and the spontaneously hypertensive rat (SHR) model of the combined type of ADHD. We found that the expression levels of these genes were significantly correlated, suggesting that they may be coregulated. Principal component analysis identified two main factors that accounted for 94% of the expression variance of the 10 genes. Significant differences were found for both factors across the 3 different rat strains. The two ADHD rat models (WKY/NCrl and SHR), although different from each other in adulthood, showed similar profiles in adolescence. Both models were significantly different from WKY/NHsd control rats at both ages. The expression abnormalities of each gene were evaluated and their roles in cell signaling processes such as calcium signaling and protein phosphorylation are discussed. Our results suggest that abnormalities in SLC9A9 mediated signaling pathways could contribute to the ADHD phenotype of two rat models (WKY/NCrl and SHR/NCrl), and that the perturbation of the SLC9A9 network is age-dependent. PMID- 22777495 TI - Epidemiology of meningioma in the United Kingdom. AB - BACKGROUND: Data on the epidemiology and aetiology of meningioma are limited. METHODS: The Health Improvement Network UK primary care database was used to ascertain incident cases of meningioma between January 1996 and June 2008. Ten thousand controls analysis were frequency-matched by age, sex and year. A nested case control analysis was performed to determine risk factors for meningioma. RESULTS: The incidence of meningioma was 5.30 per 100,000 person-years over the study period. The incidence was higher in women than in men (7.19 vs. 3.05 per 100,000 person-years). Cerebrovascular disease (OR 1.86; 95% CI 1.46-2.36) and a history of cancer, thyroid disease, epilepsy, migraine and headache and exposure to antiepileptics were significantly associated with an increased risk of meningioma. Ischemic heart disease and exposure to antiepileptics were associated with a decreased risk of meningioma. CONCLUSIONS: The incidence of meningioma in the UK remained stable over the 12-year study period and was twofold higher in women than men. Although the prevalence and incidence of meningioma remained stable during the study, further research into risk factors and predisposing conditions for the onset of meningioma and early symptoms of tumor development is warranted to improve prevention and early diagnosis of this disease. PMID- 22777496 TI - The young and happy marriage of membrane traffic and cell polarity. AB - The ESF-EMBO meeting on 'Cell Polarity and Membrane Traffic' took place in Poland in April 2012. It brought together scientists from two once separate fields and highlighted their emerging interdependence. The wealth of scientific insights and discoveries presented laid a path for future research. PMID- 22777497 TI - Measuring the societal impact of research: research is less and less assessed on scientific impact alone--we should aim to quantify the increasingly important contributions of science to society. PMID- 22777498 TI - Specific training improves skeletal muscle mitochondrial calcium homeostasis after eccentric exercise. AB - There is limited understanding of the mitochondrial adaptation following repeated eccentric exercise bouts, a model resulting in muscle adaptation known as the repeat bout effect. It was hypothesized that downhill training would reduce mitochondrial calcium content (MCC) post an acute eccentric bout with concurrent improvements in mitochondrial respiratory function. Thirty-four Sprague-Dawley rats were divided into four groups: control (N), control with acute eccentric exercise (N (ecc)), trained control (X) and trained with acute eccentric exercise (X (ecc)). Training for X and X (ecc) consisted of 30 min per day for five consecutive days of downhill treadmill running. The acute eccentric exercise bout was a -14 degrees treadmill exercise for 90 min performed 2 weeks after the training period. Animals were killed 48 h post-exercise. Isolated mitochondria from the red quadriceps allowed for the measure of mitochondrial respiratory indices and MCC. Calpain activity and heat shock protein 72 expression (HSP72) were also measured. MCC dramatically increased following the acute bout of eccentric exercise in N (ecc) (p < 0.001), but did not change in X (ecc). Mitochondrial respiratory function tended to be slightly depressed in N (ecc) (state 3 respiration, p = 0.053; respiratory control ratio, p = 0.098) and unaltered in X (ecc). Previous training altered the calpain and heat shock protein response to an acute bout of eccentric exercise. The results suggest that downhill exercise training improves mitochondrial calcium homeostasis following an acute bout of prolonged eccentric exercise and may stabilize mitochondrial respiratory function. These improvements coincide with a reduction in calpain activity and heat shock protein upregulation. PMID- 22777499 TI - Muscle gearing during isotonic and isokinetic movements in the ankle plantarflexors. AB - Muscle-tendon gearing is the ratio of the muscle-tendon unit velocity to the fascicle velocity and can be expressed as the product of the gearing within the muscle belly and the gearing due to tendon stretch. Previous studies have shown that gearing is variable and increases at higher velocities. Changes in the muscle activation levels and force development have been suggested to affect tendon gearing and thus muscle-tendon unit gearing. However, the role of belly gearing as a part of muscle-tendon gearing and its associations with structural aspects of muscle and thus movement performance are important facets that need to be studied. The two gastrocnemii of twenty young adults were tested during isokinetic and isotonic contractions on an ankle dynamometer. Ultrasound images of both muscles were collected during contractions and were later digitised. Gearing was also predicted using a 2-dimensional panel model of these muscles. The results from experimental and models tests showed increases in gearing with greater torque levels at slower contraction velocities. However, in the isotonic models there was a substantial increase in gearing at faster contraction velocities. The level of muscle-tendon unit gearing is largely determined by the belly gearing, but its variability is driven by changes in tendon gearing that in turn is a factor of the muscle activation and coordination. The belly thickness of the medial gastrocnemius decreased during contractions, but increased for the lateral gastrocnemius. It is likely that changes to the belly shape and 3 dimensional structure are important to the gearing of the muscle. PMID- 22777500 TI - Recognizing unusual manifestations of Hodgkin lymphoma. AB - Hodgkin lymphoma (HL) is a rare malignancy of the lymphatic system that is curable in at least 80 % of patients. Although patients usually present with painless lymphadenopathy, a variety of systemic and organ-specific syndromes may also exist in relation to HL. These syndromes may develop before, during, or after the diagnosis of HL and may also indicate disease relapse. Most of these unusual disorders resolve with successful HL treatment but some may require adjunctive supportive therapies before a response is achieved. Oncologists should be familiar with these syndromes because early recognition may result in a more timely diagnosis of HL which may lead to improved outcomes. PMID- 22777501 TI - The impact of Vocational, Education, Training and Employment Coordinator positions on attitudes and practices in a NSW mental health service. AB - OBJECTIVE: To determine attitudes and practices of community mental health clinicians in relation to employment and education for consumers and to assess the impact of the establishment of Vocational, Education, Training and Employment (VETE) Coordinator positions. METHOD: A snapshot was conducted by surveying community mental health clinicians regarding every consumer on their caseload in 2007. This was repeated in 2010 and the results were compared. RESULTS: From 2007 to 2010, the overall rates of VETE interventions increased, including a doubling of the rate of linkage to employment agencies for job seekers. Services with the consistent presence of a VETE Coordinator showed a greater impact on a number of factors, highlighted by a positive shift in clinician attitudes regarding their consumers' capacity to work. CONCLUSION: The establishment of VETE Coordination positions in the mental health service appears to be an effective way of raising awareness of VETE issues and improving VETE service provision. An important role has been assisting clinicians to begin implementing the principles of the Individual Placement and Support model of Supported Employment and to incorporate support for employment and education as a routine part of practice. PMID- 22777502 TI - Comments on adolescent intakes of vitamin D and calcium and incidence of proliferative benign breast disease. PMID- 22777503 TI - Teaching high-value, cost-conscious care to residents: the Alliance for Academic Internal Medicine-American College of Physicians Curriculum. AB - Health care expenditures are projected to reach nearly 20% of the U.S. gross domestic product by 2020. Up to $765 billion of this spending has been identified as potentially avoidable; many of the avoidable costs have been attributed to unnecessary services. Postgraduate trainees have historically received little specific training in the stewardship of health care resources and minimal feedback on resource utilization and its effect on the cost of care. This article describes a new curriculum that was developed collaboratively by the Alliance for Academic Internal Medicine and the American College of Physicians to address this training gap. The curriculum introduces a simple, stepwise framework for delivering high-value care and focuses on teaching trainees to incorporate high value, cost-conscious care principles into their clinical practice. It consists of ten 1-hour, case-based, interactive sessions designed to be flexibly incorporated into the existing conference structure of a residency training program. PMID- 22777505 TI - Association of FCRL4 polymorphisms on disease susceptibility and severity of ankylosing spondylitis in Chinese Han population. AB - Previous studies have found that the Fc receptor-like (FCRL) molecule, involved in controlling B cell signaling, may contribute to the autoimmune disease process. Many studies have reported the relation of FCRL gene family with SLE and RA. We hypothesized that FCRL4 may be a key gene for ankylosing spondylitis (AS) development. To test this hypothesis, we screened FCRL4 polymorphisms in the Chinese Han population. Five tag single nucleotide polymorphisms (SNPs), including rs14335, rs849826, rs10489674, rs2778003, and rs2777963, were selected. Using a case-control study, five tag SNPs, which captured the majority of known common variation within FCRL4 gene, were selected and genotyped by Multiplex Snapshot technique. We analyzed 299 patients and 300 controls from China. The genotype analysis demonstrated that one of the FCRL4 tag SNPs rs2777963 TT genotype may be a risk factor of AS (chi(2) = 7.374, p = 0.024). The haplotype analysis indicated that there were no significant differences between AS cases and controls. Patients with AS who had rs14335 AA genotype had a significantly declined visual analogue scale patient's global assessment scores compared to those with the GG genotype (31.21 +/- 26.25 vs 40.54 +/- 25.40, p = 0.035) and GA genotype (38.29 +/- 24.94 vs 40.54 +/- 25.40, p = 0.044), and in locus rs10489674, TT genotype had significantly increased Bath Ankylosing Spondylitis Disease Activity Index scores compared to those with the CC genotype (4.73 +/- 2.43 vs 3.15 +/- 1.61, p = 0.003) and CT genotype (4.73 +/- 2.43 vs 2.97 +/- 1.71, p = 0.001). The FCRL4 polymorphisms may play an important role in the susceptibility and severity of AS in the Chinese Han population. PMID- 22777506 TI - Importance of standardized methodology to comparisons between studies of rheumatoid arthritis and cardiovascular disease: comment on the article by Giles et al. PMID- 22777507 TI - Role of cerebellum in motion perception and vestibulo-ocular reflex-similarities and disparities. AB - Vestibular velocity storage enhances the efficacy of the angular vestibulo-ocular reflex (VOR) during relatively low-frequency head rotations. This function is modulated by GABA-mediated inhibitory cerebellar projections. Velocity storage also exists in perceptual pathway and has similar functional principles as VOR. However, it is not known whether the neural substrate for perception and VOR overlap. We propose two possibilities. First, there is the same velocity storage for both VOR and perception; second, there are nonoverlapping neural networks: one might be involved in perception and the other for the VOR. We investigated these possibilities by measuring VOR and perceptual responses in healthy human subjects during whole-body, constant-velocity rotation steps about all three dimensions (yaw, pitch, and roll) before and after 10 mg of 4-aminopyridine (4 AP). 4-AP, a selective blocker of inward rectifier potassium conductance, can lead to increased synchronization and precision of Purkinje neuron discharge and possibly enhance the GABAergic action. Hence 4-AP could reduce the decay time constant of the perceived angular velocity and VOR. We found that 4-AP reduced the decay time constant, but the amount of reduction in the two processes, perception and VOR, was not the same, suggesting the possibility of nonoverlapping or partially overlapping neural substrates for VOR and perception. We also noted that, unlike the VOR, the perceived angular velocity gradually built up and plateau prior to decay. Hence, the perception pathway may have additional mechanism that changes the dynamics of perceived angular velocity beyond the velocity storage. 4-AP had no effects on the duration of build-up of perceived angular velocity, suggesting that the higher order processing of perception, beyond the velocity storage, might not occur under the influence of mechanism that could be influenced by 4-AP. PMID- 22777508 TI - Immunohistochemical localization of beta defensins in the endometrium of rat uterus during the postpartum involution period. AB - beta-Defensins are small cationic molecules that have antimicrobial actions against bacteria, fungi and viruses and contribute to mucosal immune responses at epithelial sites. The female reproductive tract is an important site of defensin production. This study was conducted to determine the possible changes in proportions and localization of beta-defensin 1-4 in the rat uterus at the 1st, 3th, 5th, 10th and 15th days of postpartum and at the period of diestrus using immunohistochemical techniques. In the present study, it was determined that beta defensin 1-4 were generally found in all structural components of the endometrium (luminal and glandular epithelium, stromal cells and blood vessels) in both the nucleus and the cytoplasm of cells during the involution period and diestrus. Suprisingly, immunoreaction of beta-defensin 2 was also observed in the lateral membrane of the luminal and glandular epithelial cells on the 10th day of involution and immunostaining of beta-defensin 4 was also localized in the apical membrane of the luminal and glandular epithelial cells. The current study demonstrated beta-defensin 1-4 immunoreactivities in the endothelium of blood vessels were stronger throughout the involution period. Although beta-defensins 2 and 3 were localized in both the nuclei and the cytoplasm of endothelial cells, beta-defensins 1 and 4 were present in only cytoplasm. These results show that the most component of rat endometrium expresses human beta-defensin 1-4 in a involution-dependent manner. Therefore it may be asserted that these molecules constitute a organised protection to prevent uterus from probable infections during the involution process. PMID- 22777509 TI - How drug-eluting stents illustrate our health system's flawed relationship with technology: comment on "use of drug-eluting stents as a function of predicted benefit". PMID- 22777510 TI - Optic perineuritis as the presenting feature of Crohn disease. AB - Crohn disease (CD) is primarily considered an inflammatory condition of the small and large intestine although associated extraintestinal inflammation is relatively common. Ocular manifestations are generally localized to the anterior chamber and ocular surface but rarely can involve the posterior pole, orbit, and optic nerve. We report a case of an otherwise healthy 42-year-old man who was diagnosed with CD after presenting with acute vision loss from optic perineuritis. PMID- 22777511 TI - Morphology of the ligament of Treitz likely depends on its fetal topographical relationship with the left adrenal gland and liver caudate lobe as well as the developing lymphatic tissues: a histological study using human fetuses. AB - To investigate the factors affecting the development of the ligament of Treitz, we examined sagittal and frontal histological sections of 35 human fetuses with a crown-rump length of 100-300 mm (approximately 16-38 weeks of gestation). The retropancreatic fascia consistently extended in a layer behind the pancreatic body and the splenic artery and vein, and also in front of the left renal vein and left adrenal. In 18 specimens, a connective tissue band was seen originating from the diaphragmatic crus around the esophageal opening and ending at the retropancreatic fascia to the left of the origin of the celiac artery. In 10 of these 18 specimens, these putative upper parts of the ligament contained striated muscles, or so-called Hilfsmuskel. Although most of other 17 specimens were larger fetuses, the left adrenal, the liver caudate lobe and the celiac ganglion made space for the ligament very limited. In 22 specimens including the above 18, the retropancreatic fascia extended inferiorly to approach the fourth portion of the duodenum (D4) or the duodenojejunal junction (DJJ). However, in 11 of the 22 examples of the putative lower part of the ligament, the connection between the duodenal muscle coat and the fascia was interrupted by developing lymphatic tissues. Consequently, the ligament of Treitz seemed to develop from both pleuroperitoneal membrane-derived cells and the retropancreatic fusion fascia, although the morphology was markedly modified by adjacent structures such as the adrenal gland. The ligament may "recover" after the adrenal becomes reduced in size after birth. PMID- 22777512 TI - Anatomy and medical imaging: a symbiotic relationship. PMID- 22777513 TI - Four-decade maintenance of analgesia with percutaneous cordotomy. AB - The management of severe, medically intractable pain is a significant challenge for neurosurgeons and pain management physicians. An existing technique that can effectively alleviate contralateral chronic pain is cordotomy, interruption of the lateral spinothalamic tract of the spinal cord. Since 1912, cordotomy has evolved from a relatively morbid open surgical procedure to a percutaneous radiofrequency procedure with low morbidity. However, since cordotomy is utilized primarily in cancer pain patients, long-term patient follow-up is rare, and the potential duration of analgesia following cordotomy is not known. Here we describe a case with a 41-year follow-up of percutaneous cordotomy for noncancer pain that resulted in over 35 years of complete analgesia, the longest recorded in the literature to date. This case demonstrates that percutaneous cordotomy can provide long-lasting, complete analgesia in some patients and merits continuation as a part of the neurosurgical arsenal of pain therapies. PMID- 22777514 TI - Etomidate increases susceptibility to pneumonia in trauma patients. AB - PURPOSE: To investigate the impact of etomidate on the rate of hospital-acquired pneumonia (HAP) in trauma patients and the effects of hydrocortisone in etomidate treated patients. METHODS: This was a sub-study of the HYPOLYTE multi-centre, randomized, double-blind, placebo-controlled trial of hydrocortisone in trauma patients (NCT00563303). Inclusion criterion was trauma patient with mechanical ventilation (MV) of >=48 h. The use of etomidate was prospectively collected. Endpoints were the results of the cosyntropin test and rate of HAP on day 28 of follow-up. RESULTS: Of the 149 patients enrolled in the study, 95 (64 %) received etomidate within 36 h prior to inclusion. 79 (83 %) of 95 patients receiving etomidate and 34 of the 54 (63 %) not receiving etomidate had corticosteroid insufficiency (p = 0.006). The administration of etomidate did not alter basal cortisolemia (p = 0.73), but it did decrease the delta of cortisolemia at 60 min (p = 0.007). There was a correlation between time from etomidate injection to inclusion in the study and sensitivity to corticotropin (R (2) = 0.19; p = 0.001). Forty-nine (51.6 %) patients with etomidate and 16 (29.6 %) patients without etomidate developed HAP by day 28 (p = 0.009). Etomidate was associated with HAP on day 28 in the multivariate analysis (hazard ratio 2.48; 95 % confidence interval 1.19-5.18; p = 0.016). Duration of MV with or without etomidate was not significantly different (p = 0.278). Among etomidate-exposed patients, 18 (40 %) treated with hydrocortisone developed HAP compared with 31 (62 %) treated with placebo (p = 0.032). Etomidate-exposed patients treated with hydrocortisone had fewer ventilator days (p < 0.001). CONCLUSIONS: Among the patients enrolled in the study, etomidate did not alter basal cortisolemia, but it did decrease reactivity to corticotropin. We suggest that in trauma patients, etomidate is an independent risk factor for HAP and that the administration of hydrocortisone should be considered after etomidate use. PMID- 22777515 TI - The receptor for advanced glycation end products and acute lung injury/acute respiratory distress syndrome. AB - The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor and evolutionary member of the immunoglobulin superfamily that is involved in the host response to infection, injury, and inflammation. It exists in two forms: membrane-bound and soluble forms (sRAGE). RAGE recognizes a variety of ligands and, via a receptor-driven signaling cascade, activates the transcription factor NF-kappaB, leading to the expression of proinflammatory cytokines. The soluble form, sRAGE, is a decoy receptor and competitively inhibits membrane RAGE activation. RAGE is constitutively expressed abundantly in the lung under basal conditions. This expression is enhanced during inflammatory states such as with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This review summarizes the characteristics of RAGE, RAGE isoforms, RAGE ligands, and signaling pathways in the pathogenesis of ALI and ARDS. Additionally, the review explores the potential of RAGE as an important therapeutic target in ALI/ARDS. PMID- 22777516 TI - The variability of critical care bed numbers in Europe. AB - PURPOSE: To quantify the numbers of critical care beds in Europe and to understand the differences in these numbers between countries when corrected for population size and gross domestic product. METHODS: Prospective data collection of critical care bed numbers for each country in Europe from July 2010 to July 2011. Sources were identified in each country that could provide data on numbers of critical care beds (intensive care and intermediate care). These data were then cross-referenced with data from international databases describing population size and age, gross domestic product (GDP), expenditure on healthcare and numbers of acute care beds. RESULTS: We identified 2,068,892 acute care beds and 73,585 (2.8 %) critical care beds. Due to the heterogeneous descriptions of these beds in the individual countries it was not possible to discriminate between intensive care and intermediate care in most cases. On average there were 11.5 critical care beds per 100,000 head of population, with marked differences between countries (Germany 29.2, Portugal 4.2). The numbers of critical care beds per country corrected for population size were positively correlated with GDP (r(2) = 0.16, p = 0.05), numbers of acute care beds corrected for population (r(2) = 0.12, p = 0.05) and the percentage of acute care beds designated as critical care (r(2) = 0.59, p < 0.0001). They were not correlated with the proportion of GDP expended on healthcare. CONCLUSIONS: Critical care bed numbers vary considerably between countries in Europe. Better understanding of these numbers should facilitate improved planning for critical care capacity and utilization in the future. PMID- 22777517 TI - Safety and diagnostic yield of renal biopsy in the intensive care unit. AB - PURPOSE: Renal biopsy (RB) is occasionally performed in critically ill patients. The safety and impact of RB in this setting have not been reported. METHODS: A 10 year (2000-2009) retrospective multicentre study was conducted in ten French intensive care units (ICU) on patients who underwent RB during their management. Medical files were retrieved for data analysis. RESULTS: Seventy-seven patients underwent an RB of which 68 (88 %) were on a native kidney and 9 (12 %) on a transplanted kidney. Percutaneous ultrasound-guided RB was used in most cases (87 %). Fifty-seven per cent of the patients were on mechanical ventilation at the time of RB. RB-related complications occurred in 17 (22 %) patients, two were graded as severe (requirement for kidney embolization, eventually successful). In 35 (51 %) non-transplanted patients, RB established a specific diagnosis other than acute tubular necrosis (ATN), which was diagnosed in only 18 % of patients. In the remaining patients, only non-specific lesions were observed. Therapeutic modifications followed RB in 14 (21 %) non-transplanted patients. Presence of signs of systemic disease involving the renal tract, occurrence of renal failure before hospital admission, and absence of any factor usually associated with ATN significantly predicted the presence of a specific diagnosis at RB other than ATN. CONCLUSIONS: In this cohort, the contribution of RB to diagnosis and treatment was undeniable, but at the expense of frequent adverse events although most of them were not considered severe. PMID- 22777519 TI - World Alliance against antibiotic resistance (WAAR): safeguarding antibiotics. PMID- 22777518 TI - Red blood cell transfusion affects microdialysis-assessed interstitial lactate/pyruvate ratio in critically ill patients with late sepsis. AB - PURPOSE: The aim of this study was to explore the effect of red blood cell (RBC) transfusion on microdialysis-assessed interstitial fluid metabolic parameters in septic patients. METHODS: We conducted a retrospective study of 37 patients with severe sepsis/septic shock requiring transfusion of one to two RBC units. Interstitial fluid metabolic alterations were monitored by a microdialysis catheter inserted in the subcutaneous adipose tissue. Samples were collected before (T0) and after transfusion at two time-points: T1a and T1b; median post transfusion times of 120 [interquartile range (IQR); 45-180] and 360 (IQR; 285 320) min. Lactate, pyruvate, glycerol and glucose concentrations were measured with a bedside analyzer, and the lactate/pyruvate (LP) ratio was calculated automatically. RESULTS: RBC transfusions decreased the LP ratio from (T0) 18.80 [interquartile range (IQR); 14.85-27.45] to (T1a) 17.80 (IQR; 14.35-25.20; P < 0.05) and (T1b) 17.90 (IQR; 14.45-22.75; P < 0.001), while there was also significant interindividual variation. Post-transfusion LP ratio changes at T1a [r = -0.42; 95 % confidence interval (CI), -0.66 to -0.098; P = 0.01] and T1b (r = -0.68; 95 % [CI], -0.82 to -0.44; P < 0.001) were significantly correlated with the pre-transfusion LP ratio, but not with baseline demographic characteristics, vital signs, severity scores, hemoglobin level and blood lactate. RBC storage time and leukocyte reduction had no influence on the tissue metabolic response to transfusion. CONCLUSIONS: Tissue oxygenation is affected by RBC transfusion in critically ill septic patients. Monitoring of tissue LP ratio by microdialysis may represent a useful method for individual clinical management. PMID- 22777520 TI - Recent advances in computational actinoid chemistry. AB - We briefly review advances in computational actinoid (An) chemistry during the past ten years in regard to two issues: the geometrical and electronic structures, and reactions. The former addresses the An-O, An-C, and M-An (M is a metal atom including An) bonds in the actinoid molecular systems, including actinoid oxo and oxide species, actinoid-carbenoid, dinuclear and diatomic systems, and the latter the hydration and ligand exchange, the disproportionation, the oxidation, the reduction of uranyl, hydroamination, and the photolysis of uranium azide. Concerning their relevance to the electronic structures and reactions of actinoids and their importance in the development of an advanced nuclear fuel cycle, we also mentioned the work on actinoid carbides and nitrides, which have been proposed to be candidates of the next generation of nuclear fuel, and the oxidation of PuO(x), which is important to understand the speciation of actinoids in the environment, followed by a brief discussion on the urgent need for a heavier involvement of computational actinoid chemistry in developing advanced reprocessing protocols of spent nuclear fuel. The paper is concluded with an outlook. PMID- 22777521 TI - Complement-induced protection: an explanation for the limitations of cell-based tumour immunotherapies. AB - Complement is involved in the inflammatory response and clearance of infected or altered cells. It is therefore unexpected that complement-deficient animals are less susceptible to carcinogen-induced tumours and more readily control growth of injected tumour cell lines than their wild-type counterparts, implying that complement promotes tumour development and progression. Conversely, natural killer (NK) and CD8(+) T cells are known to limit progression of the same tumours. Previous studies indicate that sublytic levels of the complement membrane attack complex protect cells against further attack by lytic doses of complement and other pore-formers such as perforin. We hypothesise that inefficient attack by complement in vivo allows tumour cells to avoid lysis by both NK cells and antigen-specific cytotoxic T cells, thereby promoting tumour outgrowth. Complement could thus be limiting the efficacy of NK and T cell targeted cancer therapies, and the inclusion of complement inhibitors could optimise these immunotherapeutic regimes. PMID- 22777522 TI - Phosphatidylinositol-3 kinase activity in B cells is negatively regulated by Lyn tyrosine kinase. AB - Phosphatidylinositol-3 kinase (PI3K) activity is essential for normal B-cell receptor (BCR)-mediated responses. To understand the mechanisms of PI3K regulation during B-cell activation, we performed a series of biochemical analysis on primary B cells, and found that activity of Src family tyrosine kinases (SFK) is crucial for the activation of PI3K following BCR ligation and this is regulated by the SFK Lyn. We show that the hyperresponsive phenotype of B cells lacking Lyn is predicated on significantly increased basal and inducible PI3K activity that correlates with the constitutive hypophosphorylation of PAG/Cbp (phosphoprotein associated with glycosphingolipid-enriched microdomains/Csk-binding protein), a concomitant reduction in bound Csk in Lyn(-/ ) B cells and elevated levels of active Fyn. Regulating SFK activity may thus be a central mechanism by which Lyn regulates PI3K activity in B cells. This study defines the molecular connection between the BCR and PI3K and reveals this to be a point of Lyn-mediated regulation. PMID- 22777523 TI - Schizophrenia and substance abuse comorbidity: nicotine addiction and the neonatal quinpirole model. AB - This review focuses on nicotine comorbidity in schizophrenia, and the insight into this problem provided by rodent models of schizophrenia. A particular focus is on age differences in the response to nicotine, and how this relates to the development of the disease and difficulties in treatment. Schizophrenia is a particularly difficult disease to model in rodents due to the fact that it has a plethora of symptoms ranging from paranoia and delusions of grandeur to anhedonia and negative affect. The basis of these symptoms is believed to be due to neurochemical abnormalities and neuropathology in the brain, which most models have attempted to emulate. A brief review of findings regarding nicotine use and abuse in schizophrenics is presented, with findings using rodent models that have been able to provide insight into the mechanisms of addiction. A common clinical approach to the treatment of nicotine addiction in the schizophrenic population has been that these drugs are used for self-medication purposes, and it is clear that self-medication may actually be directed at several symptoms, including cognitive impairment and anhedonia. Finally, our laboratory has reported across a series of studies that neonatal treatment with the dopamine D(2)/D(3) receptor agonist quinpirole results in long-term increases in dopamine-like receptor sensitivity, consistent with data reporting increases in dopamine D(2) receptor function in schizophrenia. Across these studies, we have reported several behavioral, neurochemical, and genetic consistencies with the disease, and present a hypothesis for what we believe to be the basis of psychostimulant addiction in schizophrenia. PMID- 22777524 TI - Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis. AB - BACKGROUND: Patients with diabetes mellitus need information about the effectiveness of innovations in insulin delivery and glucose monitoring. PURPOSE: To review how intensive insulin therapy (multiple daily injections [MDI] vs. rapid-acting analogue-based continuous subcutaneous insulin infusion [CSII]) or method of monitoring (self-monitoring of blood glucose [SMBG] vs. real-time continuous glucose monitoring [rt-CGM]) affects outcomes in types 1 and 2 diabetes mellitus. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through February 2012 without language restrictions. STUDY SELECTION: 33 randomized, controlled trials in children or adults that compared CSII with MDI (n=19), rt-CGM with SMBG (n=10), or sensor augmented insulin pump use with MDI and SMBG (n=4). DATA EXTRACTION: 2 reviewers independently evaluated studies for eligibility and quality and serially abstracted data. DATA SYNTHESIS: In randomized, controlled trials, MDI and CSII showed similar effects on hemoglobin A1c (HbA1c) levels and severe hypoglycemia in children or adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus. In adults with type 1 diabetes mellitus, HbA1c levels decreased more with CSII than with MDI, but 1 study heavily influenced these results. Compared with SMBG, rt-CGM achieved a lower HbA1c level (between-group difference of change, 0.26% [95% CI, 0.33% to 0.19%]) without any difference in severe hypoglycemia. Sensor-augmented insulin pump use decreased HbA1c levels more than MDI and SMBG did in persons with type 1 diabetes mellitus (between group difference of change, 0.68% [CI, 0.81% to 0.54%]). Little evidence was available on other outcomes. LIMITATION: Many studies were small, of short duration, and limited to white persons with type 1 diabetes mellitus. CONCLUSION: Continuous subcutaneous insulin infusion and MDI have similar effects on glycemic control and hypoglycemia, except CSII has a favorable effect on glycemic control in adults with type 1 diabetes mellitus. For glycemic control, rt-CGM is superior to SMBG and sensor-augmented insulin pumps are superior to MDI and SMBG without increasing the risk for hypoglycemia. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. PMID- 22777525 TI - Very low-activity stress/high-activity rest, single-day myocardial perfusion SPECT with a conventional sodium iodide camera and wide beam reconstruction processing. AB - BACKGROUND: A stress (S)/rest (R) 1-day Tc-99m sestamibi protocol is logistically advantageous and facilitates stress-only imaging. However, with conventional 370 MBq (10 mCi) S activity and subsequent 1,110-1,295 MBq (30-35 mCi) R activity there is a risk of S-to-R "shine-through" and underestimation of defect reversibility. New software methods cope with lower counting statistics and should allow for both a reduced S activity and also less likelihood of S-to-R "shine-through." METHODS: 102 prospective patients [49 men, 53 women; mean weight 178 +/- 41 lbs (range 98-265 lbs); chest 41.5" +/- 4.0" (range 32"-52")] received 192.4 + 18.5 MBq (5.2 +/- 0.5 mCi) Tc-99m sestamibi S (25 exercise, 77 regadenoson) activity followed in 30-40 minutes by "full-time" (12 minutes) two headed NaI camera S SPECT. Immediately thereafter, a 16-minute S SPECT acquisition was also performed in 37/102 patients. Then at 60-80 minute post-S all patients received 1328.3 + 129.5 MBq (35.9 +/- 3.5 mCi) Tc-99m sestamibi, and "half-time" (7.5 minutes) R SPECT was acquired. All tomograms were processed with wide beam reconstruction (WBR, UltraSPECT Ltd.) software. A time-adjusted R/S myocardial count density ratio (MCDR) was calculated using automated software. S SPECT quality was visually graded (poor, fair, good, excellent) based upon myocardial definition, cavity contrast, RV visualization, and noise. For comparison, the S/R MCDR was calculated in 581 consecutive patients undergoing a conventional 370 MBq R/1110 MBq S (10 mCi R/30 mCi S) protocol. RESULTS: S SPECT was normal in 44 patients (43%). Image quality was good-excellent in 93 (91%) patients with 12-minute S SPECT. Also in 37 (98%) patients with 16-minute S SPECT, quality was good-excellent. In patients with >42" chests 12-minute S SPECT quality worsened with increasing chest circumference, manifested by myocardial "blurring." Image quality improved by >=1 grade in the 12/37 patients (32%) also undergoing 16-minute S SPECT. The time- and decay-corrected 12-minute mean R/S MCDR was 5.78, a ratio adequate to minimize S-to-R shine-through, as verified in phantom experiments, and significantly better than a 3.79 S/R ratio achieved in the 581 patients undergoing a conventional R/S protocol. CONCLUSIONS: An approximately 185 MBq (5 mCi S) Tc-99m SPECT processed with WBR provides adequate image quality. For larger patients prolonging image acquisition to 16 minutes is beneficial. For patients with normal S SPECT, a S-only protocol is feasible, affording them a very low (approximately 1.4 mSv) radiation dose. If subsequent R SPECT is necessary, it can be performed with approximately 1,332 MBq (36 mCi) with minimal S-R "shine-through." PMID- 22777526 TI - Trends in teenage termination of pregnancy and its risk factors: a population based study in Finland, 1987-2009. AB - STUDY QUESTION: What are the current trends in teenage termination of pregnancy (TOP) and its risk factors? SUMMARY ANSWER: The incidence of teenage TOP fluctuated substantially during the study period and the incidence of repeat TOP among adolescents increased markedly in the 2000s. WHAT IS KNOWN ALREADY: Teenage pregnancy is associated with difficulties in psychological, sexual and overall health. The proportion of teenage pregnancies resulting in termination varies by country and time, but only few countries have reliable statistics on TOPs. STUDY DESIGN, SIZE, DURATION: This nationwide retrospective register study included all the TOPs (n= 52 968) and deliveries (n= 58 882) in Finland between 1987 and 2009 among girls <20 years of age at the beginning of pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: The cohorts were divided into three subgroups; 13-15- (n= 6087), 16-17- (n= 18 826) and 18-19- (n= 28 055) year-olds. MAIN RESULTS AND THE ROLE OF CHANCE: After an initial steady decline, the incidence of teenage TOP increased by 44% between 1993 (8.0/1000) and 2003 (11.5/1000), and thereafter declined by 16% until 2009 (9.7/1000). The incidence was higher in older adolescents, but the trends were alike in all age groups. Early TOPs (performed at <56 days of gestation) more than tripled from 11 to 36% during the study period. However, the proportion of second-trimester TOPs remained steady at ~ 7%. Young age [13-15 years: odds ratio (OR) 1.75 (95% confidence interval (CI) 1.57-1.94), 16-17 years: OR 1.13 (1.05-1.23), 18-19 years: OR 1 (reference category)] and non-use of contraception [(OR 11.16 (10.15 12.27)] were related to a higher risk of second-trimester TOP. The incidence of repeat TOP increased by 95% from 1.9/1000 to 3.7/1000 in 18-19-year-olds and by 120% from 0.5/1000 to 1.1/1000 in 16-17-year-olds between 1993 and 2009. Increasing age [13-15 years: OR 0.16 (95% CI 0.14-0.19), 16-17 years: OR 0.49 (0.45-0.52), 18-19 years 1 (Ref)], living in an urban area [rural: OR 0.62 (0.56 0.67), urban: OR 1 (Ref)] and having undergone a second-trimester TOP [OR 1.46 (1.31-1.63)] were risk factors for repeat TOP. The planned use of intrauterine contraception for post-abortal contraception increased from 2.6 to 6.2% and among girls with repeat TOP from 10 to 19%. LIMITATIONS: The retrospective nature of the study remains a limitation and the quality of the data is reliant on the accuracy of reporting. We were not able to link repeat TOPs of the same woman in our data set. However, the share of repeat abortions was moderate. WIDER IMPLICATIONS OF THE FINDINGS The rate of teenage TOP seems to rapidly reflect changes in national sexual and reproductive health services and policy. The rising rate of repeat TOP is alarming and may represent a sign of marginalization among these girls. All efforts to maintain a low rate of teenage pregnancy are welcomed. PMID- 22777527 TI - Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. AB - STUDY QUESTION: What is the prevalence, phenotype and metabolic features of polycystic ovary syndrome (PCOS) in the same population according to three different diagnostic criteria? SUMMARY ANSWER: The prevalence of PCOS under National Institutes of Health (NIH), Rotterdam and Androgen Excess and PCOS (AE PCOS) Society criteria was 6.1, 19.9 and 15.3%, respectively. PCOS carried a 2 fold increased risk of metabolic syndrome regardless of the diagnostic criteria used. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: The prevalence rates of PCOS differ depending on the diagnostic criteria used to define the syndrome. The current paper gives the prevalence rates of the component and composite phenotypes of PCOS in the same population and reports similar rates of metabolic syndrome in women with PCOS under contrasting diagnostic criteria. DESIGN: In this cross sectional study, 392 women between the ages of 18 and 45 years were analyzed. PARTICIPANTS AND SETTING: When the prevalence of PCOS according to NIH was set to 8% with a precision of 2.2% and confidence interval of 95%, the sample size required for a prevalence survey was found to be 400 subjects. The study was carried out in the General Directorate of Mineral Research and Exploration, a government-based institute, in which the largest number of female staff (n = 527) are employed within a single institute in Ankara, Turkey. The study was performed between 7 December 2009 and 30 April 2010. All female subjects between the ages of 18 and 45 years were invited to participate. Women older than 45 or younger than 18 years, post-menopausal women, women with a history of hysterectomy or bilateral oopherectomy and pregnant women were excluded. Totally, 392 of the employees were recruited for the final analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of PCOS under NIH, Rotterdam and AE-PCOS Society criteria were 6.1, 19.9 and 15.3%, respectively. While the prevalence of metabolic syndrome was 6.1% in the whole study group, within the patients diagnosed as PCOS according to NIH, Rotterdam and AE-PCOS Society criteria, it was 12.5, 10.3 and 10.0%, respectively. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: Even though we have included women working at a single institution with a high response rate for the participation, we cannot exclude potential selection bias due to undetermined differences between our sample and background community. We might have underestimated actual prevalence of metabolic syndrome in PCOS due to lack of oral glucose tolerance test 2 h glucose data. GENERALIZABILITY TO OTHER POPULATIONS: Current results can be generalized to Caucasian populations and may present variations in other populations according to race and ethnicity. STUDY FUNDING/COMPETING INTEREST(S): This work was, in part, sponsored by Merck Serono. TRIAL REGISTRATION NUMBER: Not applicable. PMID- 22777528 TI - Cryptorchidism-induced CFTR down-regulation results in disruption of testicular tight junctions through up-regulation of NF-kappaB/COX-2/PGE2. AB - STUDY QUESTION: Does elevated temperature-induced cystic fibrosis transmembrane conductance regulator (CFTR) down-regulation in Sertoli cells in cryptorchid testis disrupt testicular tight junctions (TJs) through the nuclear factor kappa B (NF-kappaB)/cyclooxygenase-2 (COX-2)/prostaglandin E(2) (PGE(2)) pathway? SUMMARY ANSWER: Our results suggest that CFTR may be involved in regulating testicular TJs and the blood-testis barrier (BTB) through its negative regulation of the NF-kappaB/COX-2/PGE(2) pathway in Sertoli cells, a defect of which may result in the spermatogenesis defect in cryptorchidism. WHAT IS KNOWN ALREADY: Cryptorchidism, or undescended testes, is known to result in defective spermatogenesis. Although an elevated testicular temperature is regarded as an important factor affecting spermatogenesis in cryptorchidism, the exact mechanism remains elusive. It is known that the expression of functional CFTR is temperature sensitive. Our previous study has demonstrated that CFTR negatively regulates NF-kappaB/COX-2/PGE(2) in bronchial epithelial cells. Disruption of TJs by COX-2/PGE(2) has been found in tumour cells. STUDY DESIGN AND METHODS: Expression of CFTR, NF-kappaB, COX-2 and TJ proteins was examined in the testes of a surgical-induced cryptorchidism mouse model and a testicular hyperthermia mouse model, as well as in control or CFTR-inhibited/knocked down primary rat Sertoli cells. PGE(2) production was measured by ELISA. Sertoli cell barrier function was determined by transepethelial resistance (TER) measurements in rat Sertoli cell primary cultures. BTB integrity in the cryptorchidism model was monitored by examining tracker dye injected into seminiferous tubules. MAIN RESULTS: Down-regulation of CFTR accompanied by activation of NF-kappaB, up regulation of COX-2 and down-regulation of TJ proteins, including ZO-1 and occludin, was observed in a cryptorchidism mouse model. BTB leakage revealed impaired BTB integrity in cryptorchid testes, confirming the destruction of TJs. The inverse correlation of CFTR and COX-2 was further confirmed in a mouse testis hyperthermia model and CFTR knockout mouse model. Culturing primary Sertoli cells at 37 degrees C, which mimics the pathological condition of cryptorchidism, led to a significant decrease in CFTR and increase in COX-2 expression and PGE(2) production compared with the culture at the physiological 32 degrees C. Inhibition or knockdown of CFTR led to increased COX-2 but decreased ZO-1 and occludin expression in Sertoli cells, which could be mimicked by PGE(2), but reversed by NF-kappaB or COX-2 inhibitor, suggesting that the regulation of TJs by CFTR is mediated by a NF-kappaB/COX-2/PGE(2) pathway. Inhibition of CFTR or administration of PGE(2) significantly decreased Sertoli cell TER. LIMITATIONS: This study has tested only the CFTR/NF-kappaB/COX-2/PGE(2) pathway in mouse testes in vivo and in rat Sertoli cells in vitro, and thus, it has some limitations. Further investigations in other species, especially humans, are needed. WIDER IMPLICATIONS OF THE FINDINGS: Our study may shed more light on one of the aspects of the complicated underlying mechanisms of defective spermatogenesis induced by cryptorchidism. PMID- 22777529 TI - Ovarian stimulation leads to shorter stature in childhood. AB - BACKGROUND: We aimed to determine whether children conceived with ovarian stimulation alone (OS(A)) would differ phenotypically and biochemically from naturally conceived children of fertile and subfertile parents. METHODS: Healthy pre-pubertal children aged 3-10 years, born at term, after singleton pregnancies were recruited in Auckland (New Zealand) and were allocated into three groups: (i) children conceived following OS(A) and naturally conceived children of (ii) subfertile and (iii) fertile parents. Anthropometric, endocrine and metabolic parameters were recorded. Children's heights and body mass index (BMI) were expressed as standard deviation scores (SDS) and corrected for genetic potential (i.e. parental height or BMI). RESULTS: Three hundred fifty-two children were studied: 84 OS(A) subjects and 268 naturally conceived controls consisting of 54 children of subfertile parents and 214 children of fertile parents. Children of subfertile and fertile parents did not differ in measured outcomes. Overall, OS(A) children were shorter than children of both subfertile (SDS: -0.08 +/- 0.09 versus 0.32 +/- 0.07; P= 0.001) and fertile (SDS: -0.08 +/- 0.09 versus 0.45 +/- 0.10; P= 0.004) parents when corrected for genetic height potential. OS(A) boys were shorter than boys of subfertile (SDS:-0.18 +/- 0.14 versus 0.42 +/- 0.16; P= 0.03) and fertile (SDS: -0.18 +/- 0.14 versus 0.35 +/- 0.08; P= 0.01) parents. There was also a trend towards OS(A) girls being shorter than girls of subfertile parents (P= 0.06), but not significantly shorter than those of fertile parents (P= 0.17). OS(A) children also had a lower corrected BMISDS than children of subfertile (SDS-0.90 +/- 0.15 versus -0.37 +/- 0.17; P= 0.06) and fertile (-0.90 +/- 0.15 versus -0.34 +/- 0.10; P= 0.008) parents. Among metabolic parameters, fasting glucose was lower in OS(A) children than that in children of fertile parents (4.62 +/- 0.07 versus 4.81 +/- 0.04; P= 0.006). CONCLUSIONS: Conception after OS(A) was associated with shorter stature, particularly in boys, compared with naturally conceived children of fertile and subfertile parents. PMID- 22777530 TI - Anti-Mullerian hormone: poor assay reproducibility in a large cohort of subjects suggests sample instability. AB - STUDY QUESTION: What is the variability of anti-Mullerian hormone (AMH) concentration in repeat samples from the same individual when using the Gen II assay and how do values compare to Gen I [Diagnostic Systems Ltd (DSL)] assay results? SUMMARY ANSWER: The Gen II AMH assay displayed appreciable variability, which can be explained by sample instability. WHAT IS KNOWN ALREADY: AMH is the primary predictor of ovarian performance and is used to tailor gonadatrophin dosage in cycles of IVF/ICSI and in other routine clinical settings. Thus, a robust, reproducible and sensitive method for AMH analysis is of paramount importance. The Beckman Coulter Gen II ELISA for AMH was introduced to replace earlier DSL and Immunotech assays. The performance of the Gen II assay has not previously been studied in a clinical setting. STUDY DESIGN, SIZE AND DURATION: We studied an unselected group of 5007 women referred for fertility problems between 1 September 2008 and 25 October 2011; AMH was measured initially using the DSL AMH ELISA and subsequently using the Gen II assay. AMH values in the two assays were compared using a regression model in log(AMH) with a quadratic adjustment for age. Additionally, women (n = 330) in whom AMH had been determined in different samples using both the DSL and Gen II assays (paired samples) identified and the difference in AMH levels between the DSL and Gen II assays was estimated using the age-adjusted regression analysis. A subset of 313 women had repeated AMH determinations (n = 646 samples) using the DSL assay and 87 women had repeated AMH determinations using the Gen II assay (n = 177 samples) were identified. A mixed effects model in log(AMH) was utilized to estimate the sample to-sample (within-subject) coefficients of variation of AMH, adjusting for age. Laboratory experiments including sample stability at room temperature, linearity of dilution and storage conditions used anonymized samples. MAIN RESULTS AND THE ROLE OF CHANCE: In clinical practice, Gen II AMH values were ~20% lower than those generated using the DSL assay instead of the 40% increase predicted by the kit manufacturer. Both assays displayed high within-subject variability (Gen II assay CV = 59%, DSL assay CV = 32%). In the laboratory, AMH levels in serum from 48 subjects incubated at RT for up to 7 days increased progressively in the majority of samples (58% increase overall). Pre-dilution of serum prior to assay, gave AMH levels up to twice that found in the corresponding neat sample. Pre mixing of serum with assay buffer prior to addition to the microtitre plate gave higher readings (72% overall) compared with sequential addition. Storage at -20 degrees C for 5 days increased AMH levels by 23% compared with fresh samples. The statistical significance of results was assessed where appropriate. LIMITATIONS, REASONS FOR CAUTION: The analysis of AMH levels is a retrospective study and therefore we cannot entirely rule out the existence of differences in referral practices or changes in the two populations. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggests that AMH may not be stable under some storage or assay conditions and this may be more pronounced with the Gen II assay. The published conversion factors between the Gen II and DSL assays appear to be inappropriate for routine clinical practice. Further studies are urgently required to confirm our observations and to determine the cause of the apparent instability. In the meantime, caution should be exercised in the interpretation of AMH levels in the clinical setting. CONFLICT OF INTEREST/STUDY FUNDING: S. Roberts is supported by the NIHR Manchester Biomedical Research Centre. PMID- 22777532 TI - Temporal trends in ischemic and hemorrhagic strokes in Northern Italy: results from the cardiovascular monitoring unit in Northern Italy population-based register, 1998-2004. AB - BACKGROUND: We compared rates and case fatality from a population-based stroke register in Northern Italy between 1998 and 2004 to assess changes over time and to evaluate changes in case diagnosis and management. METHODS: The WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease criteria were used to identify suspected fatal or nonfatal events occurring among residents 35-74 years of age. Data on in-hospital treatments, symptoms and diagnostic tools were extracted. Out-of-hospital deaths were also investigated. The annual average relative change (ARC) in death rate, attack rate and case fatality were derived from Poisson models. RESULTS: Death rates due to ischemic stroke (IS) decreased [men: ARC -12.7, 95% confidence interval (CI) -21.3 to 3.2; women: ARC -14.0, 95% CI -23.3 to -3.5]. These reductions are attributable to decreases in case fatality; attack rates of nonfatal IS increased (men: ARC 3.6, 95% CI 0.5-6.7; women: ARC 4.1, 95% CI 0.0-8.2). IS patients showed a higher prevalence of dyslipidemia and hypertension and underwent MRI more frequently in 2004. Both findings may explain the increased proportions of less severe cases. Case fatality and attack rates for hemorrhagic strokes (HS) were stable, with an observed increased prevalence of patients under anticoagulant/antiplatelet treatments. CONCLUSIONS: In this low-IS-incidence population, death rates decreased substantially during the investigated period. More accurate diagnostic tools increase the probability of detecting less severe cases. HS remains a frequently fatal disease with a stable incidence. PMID- 22777531 TI - Benign multiple sclerosis: does it exist? AB - Although the definition of benign multiple sclerosis (BMS) remains controversial, it is generally applied to a subgroup of MS patients showing little disease progression, with minimal disability decades after disease onset, and is based mainly on changes in motor function. Recent studies, however, reveal that deterioration of cognitive function, fatigue, pain, and depression also occur in BMS patients, causing negative impact on work and social activities, despite complete preservation of motor function. Using conventional MRI techniques, lesion load observed in BMS is similar to levels in other disease subtypes; however, newer quantitative MRI techniques show less tissue damage, as well as greater repair and compensatory efficiency following MS injury. Currently accepted criteria for BMS diagnosis may cause overestimation of true prevalence, underscoring the need for routine monitoring of nonmotor symptoms and imaging studies. Clearly, the definition of BMS currently applied in clinical practice requires reassessment. PMID- 22777533 TI - Simulation of pyrite oxidation in fresh mine tailings under near-neutral conditions. AB - Sulphidic residual products from ore processing may produce acid rock drainage, when exposed to oxygen and water. Predictions of the magnitude of ARD and sulphide oxidation rates are of great importance in mine planning because they can be used to minimize or eliminate ARD and the associated economic and environmental costs. To address the lack of field data of sulphide oxidation rate in fresh sulphide-rich tailings under near-neutral conditions, determination and simulation of the rate was performed in pilot-scale at Kristineberg, northern Sweden. The quality of the drainage water was monitored, along with oxygen and carbon dioxide concentrations. The chemical composition of the solid tailings was also determined. The field data were compared to predictions from simulations of pyrite oxidation using a 1-D numerical model. The simulations' estimates of the amount of Fe and S released over a seven year period (52 kg and 178 kg, respectively) were in reasonably good agreement with those obtained by analysing the tailings (34 kg and 155 kg, respectively). The discrepancy is probably due to the formation of secondary precipitates such as iron hydroxides and gypsum; which are not accounted for in the model. The observed mass transport of Fe and S (0.05 and 1.0 kg per year, respectively) was much lower than expected on the basis of the simulations and the core data. Neutralization reactions involving carbonates in the tailings result in a near-neutral pH at all depths except at the oxidation front (pH < 5), indicating that the dissolution of carbonates was too slow for the acid to be neutralized, which instead neutralized deeper down in the tailings. This was also indicated by the reduced abundance of solid Ca at greater depths and the high levels of carbon dioxide both of which are consistent with the dissolution of carbonates. It could be concluded that the near-neutral pH in the tailings has no decreasing effect on the rate of sulphide oxidation, but does reduce the concentrations of dissolved elements in the drainage water due to the formation of secondary minerals. This means that sulphide oxidation rates may be underestimated if determined from drainage alone. PMID- 22777534 TI - Relationship Between Fuchs Endothelial Corneal Dystrophy Severity and Glaucoma and/or Ocular Hypertension. AB - OBJECTIVE To investigate whether Fuchs endothelial corneal dystrophy (FECD) severity is associated with glaucoma and/or ocular hypertension (G/OHTN). METHODS A subset of eyes (n = 1610) from the FECD Genetics Multi-Center Study were examined to estimate the association between FECD severity (grades 0-6 based on guttae confluence) and G/OHTN. Logistic regression models that accounted for the correlation between eyes and adjusted for age, sex, central corneal thickness, intraocular pressure, presence of diabetes, and time of day of the initial evaluation were fit. RESULTS A total of 107 eyes (6.6%) had G/OHTN based on the study definition. The prevalence of G/OHTN in the control group was 6.0%. The prevalence was lower in index cases with an FECD grade of 1 through 3 and family members with a grade of 0 or 1 through 3 (0.0% and 2.1%, respectively) but higher in index cases and family members with a grade of 4 through 6 (11.2% and 8.5%, respectively). Adjusting for covariates, eyes with a grade of 4 through 6 were more likely to have concurrent G/OHTN than eyes with no FECD (index cases vs controls: odds ratio [OR] = 2.10, P = .04; affected vs unaffected family members: OR = 7.06, P = .07). Age (OR = 1.06 per 1-year increase, P < .001) and intraocular pressure (OR = 1.15 per 1-mm Hg increase, P < .001) were also associated with an increased prevalence of G/OHTN. Sex, diabetes, time of day of evaluation, and central corneal thickness were not associated with the prevalence of G/OHTN (P >= .15). CONCLUSIONS Glaucoma and/or ocular hypertension occurs more often in eyes with severe FECD compared with unaffected eyes. Therefore, it may be beneficial to monitor for the development of glaucoma in these patients. PMID- 22777535 TI - Totally laparoscopic complete resection of the remnant stomach for gastric cancer. AB - BACKGROUND: In patients having carcinoma in the remnant stomach, total resection of the remnant stomach with lymph node dissection is a prerequisite. MATERIALS AND METHODS: We present the first series of successful totally laparoscopic complete gastrectomy (TLCG) for gastric remnant cancer. RESULTS: TLCG was successfully performed without adverse events during surgery in five patients with gastric remnant cancer. The median age of the patients was 72 years (range, 56-84 years), and there were three men and two women. Three of them had a Billroth I reconstruction and two had a Billroth II reconstruction, and in four cases following partial gastrectomy for gastric cancer and one for gastroduodenal ulcer. The median operative time was 360 min; blood loss was 20 ml. The median number of retrieved lymph nodes was 19. No complications occurred postoperatively, and all of the patients were discharged within the ninth postoperative day. CONCLUSIONS: Although TLCG for gastric remnant cancer is a technically difficult and challenging operation that requires careful lysis of adhesion and dissection along the major vessels, as well as intracorporeal anastomosis, this procedure is technically feasible. Long-term follow-up is mandatory to validate oncological outcome. PMID- 22777536 TI - Use of drug-eluting stents as a function of predicted benefit: clinical and economic implications of current practice. AB - BACKGROUND: Benefits of drug-eluting stents (DES) in percutaneous coronary intervention (PCI) are greatest in those at the highest risk of target-vessel revascularization (TVR). Drug-eluting stents cost more than bare-metal stents (BMS) and necessitate prolonged dual antiplatelet therapy (DAPT), which increases costs, bleeding risk, and risk of complications if DAPT is prematurely discontinued. Our objective was to assess whether DES are preferentially used in patients with higher predicted TVR risk and to estimate if lower use of DES in low-TVR-risk patients would be more cost-effective than the existing DES use pattern. METHODS: We analyzed more than 1.5 million PCI procedures in the National Cardiovascular Data Registry (NCDR) CathPCI registry from 2004 through 2010 and estimated 1-year TVR risk with BMS using a validated model. We examined the association between TVR risk and DES use and the cost-effectiveness of lower DES use in low-TVR-risk patients (50% less DES use among patients with <10% TVR risk) compared with existing DES use. RESULTS: There was marked variation in physicians' use of DES (range 2%-100%). Use of DES was high across all predicted TVR risk categories (73.9% in TVR risk <10%; 78.0% in TVR risk 10%-20%; and 83.2% in TVR risk >20%), with a modest relationship between TVR risk and DES use (relative risk, 1.005 per 1% increase in TVR risk [95% CI, 1.005-1.006]). Reducing DES use by 50% in low-TVR-risk patients was projected to lower US health care costs by $205 million per year while increasing the overall TVR event rate by 0.5% (95% CI, 0.49%-0.51%) in absolute terms. CONCLUSIONS: Use of DES in the United States varies widely among physicians, with only a modest correlation to patients' risk of restenosis. Less DES use among patients with low risk of restenosis has the potential for significant cost savings for the US health care system while minimally increasing restenosis events. PMID- 22777538 TI - Globus pallidus interna deep brain stimulation improves chorea and functional status in a patient with chorea-acanthocytosis. AB - We report a 39-year-old woman with chorea-acanthocytosis (ChAc) who was referred with refractory hyperkinetic movement and truncal bending spasm. She was diagnosed with ChAc with clinical features and laboratory findings of acanthocytosis in peripheral blood smear, and genetic studies revealed novel mutations in the VPS13 gene. Because her symptoms did not respond well to medical treatment, she was in a totally dependent state. We decided to perform globus pallidus interna deep brain stimulation (GPi-DBS) for symptom control. After the operation her hyperkinetic movement, bradykinesia, and truncal bending motion were improved, the preoperative total score of the motor section on the Unified Huntington's Disease Rating Scale (UHDRS) was 44, the independence scale was 50, and functional capacity was 1. However, a year after GPi-DBS, the postoperative score on the motor section was 12, the independence scale was 80, functional capacity was 9, and she had become capable of independent daily life. Although there is currently no curative treatment for ChAc, GPi-DBS represents a promising option for symptomatic control. PMID- 22777537 TI - Adult rat mesenchymal stem cells delay denervated muscle atrophy. AB - To evaluate the function of rat mesenchymal stem cells (rMSCs) on denervated gastrocnemius muscles and to address the role of ciliary neurotrophic factor (CNTF) in rMSCs, denervated Wistar rats were separately injected with culture media (sham control), CNTF protein, 2.5 * 10(5) siCNTF-treated rMSCs, 2.5 * 10(5) GFP-transfected rMSCs, or 2.5 * 10(5) untreated rMSCs. Muscle function was assessed at different time points post-surgery. Tibial nerve and gastrocnemius muscle samples were taken at 4, 8, and 12 weeks for histochemistry, and neuromuscular junction repair was also examined by electron microscopy. Fluorescence immunocytochemistry on tissue sections confirmed neurotrophin expression in rMSCs but with little evidence of neuronal differentiation. The engraftment of rMSCs significantly preserved the function of denervated gastrocnemius muscle based both on evaluation of muscle function and direct examination of muscle tissue. Further, the density and depth of the junctional folds were visibly reduced 12 weeks after surgery and transplantation, especially in control group. Knockdown of CNTF expression in rMSCs failed to block muscle preservation, although administration of CNTF protein alone inhibited muscle atrophy, which indicating that delivery of rMSCs could preserve gastrocnemius muscle function following denervation and post-junctional mechanisms involved in the repairing capability of rMSCs. PMID- 22777539 TI - A contribution for a more accurate estimation of the incidence of Kaposi sarcoma in Mozambique. PMID- 22777540 TI - Accessory anterolateral portal in arthroscopic PCL reconstruction. AB - PURPOSE: To evaluate the clinical and radiological results of arthroscopic PCL reconstruction using an accessory anterolateral portal for femoral tunneling and to compare these results with those of the conventional technique. METHODS: We retrospectively reviewed the clinical and radiological results for 57 patients who underwent PCL reconstruction, including 31 patients who underwent arthroscopic PCL reconstruction with an accessory anterolateral portal (group A) and 26 patients who underwent conventional arthroscopic PCL reconstruction (group B). Lysholm score, IKDC score, simple radiographs (AP and lateral), and posterior drawer test results were evaluated preoperatively and at 3 years postoperatively. RESULTS: No major complication was observed in group A. However, posterior cortical disruption due to improper placement of the femoral tunnel was observed in one patient in group B. The mean Lysholm knee scores increased from 41.5 +/- 4.8 preoperatively to 92.5 +/- 6.2 at final follow-up in group A (P < 0.001), and from 43.5 +/- 3.4 preoperatively to 88.5 points +/- 3.7 in group B (P = 0.002). Posterior stress radiographs with a KT-1000 showed that the mean side-to-side differences improved from 13.79 +/- 5.1 mm preoperatively to 3.1 +/- 0.7 mm postoperatively in group A and from 12.68 +/- 6.3 mm preoperatively to 3.5 +/- 0.5 mm postoperatively in group B. The sensitivity and specificity of the placement and direction of the femoral tunnel were significantly higher in group A than group B (P = 0.002). CONCLUSION: Arthroscopic PCL reconstruction with an accessory anterolateral portal can provide a better surgical view than the conventional technique, and this can minimize the problems associated with femoral tunneling, such as inappropriate and inconsistent placement of the tunnel, abnormal angulation, and sliding of the guide tip. Moreover, this approach may have a shorter operative time and a better functional recovery than the conventional technique. LEVEL OF EVIDENCE: Retrospective comparative study, Level IV. PMID- 22777541 TI - The epidemiology of weight counseling for adults in the United States: a case of positive deviance. AB - Weight counseling for adults is uncommonly performed by primary-care providers (PCPs), despite recommendations. In order to design effective primary-care interventions, a full understanding of the epidemiology of weight counseling in primary care is needed. Our objective was to measure the frequency of weight counseling at the level of the PCP. We performed a cross-sectional study of 21 220 US adult outpatient primary-care visits with 954 PCPs in 2007-2008, using data from the National Ambulatory Medical Care Survey (NAMCS). Most (58%) PCPs performed no weight counseling during any patient visits. A total of 85 (8.9%) PCPs provided 52% of all weight counseling and were categorized as 'positive deviant' (PD) physicians. Patients seeing PD physicians were older, less likely to be female and more likely to have hypertension, diabetes and obesity. Adjusting for patient characteristics strengthened the association between PD status and receipt of weight counseling during visits (adjusted odds ratio=13.2 (95% confidence interval 11.5-15.7)). In conclusion, a minority of PCPs provide the majority of primary-care weight counseling in the United States. Studies of these PCPs may help to identify practical methods to increase weight counseling in primary-care settings. PMID- 22777543 TI - Motivating or stigmatizing? Public perceptions of weight-related language used by health providers. AB - BACKGROUND: Research demonstrates that health providers express negative attitudes toward overweight and obese patients that can be conveyed through weight-related language, yet little is known about people's perceptions of weight related language used by providers. The current study examined public preferences and perceptions of weight-based terminology used by health-care providers to describe excess weight. METHOD: A national sample of American adults (N=1064) completed an online survey to assess perceptions and preferences associated with 10 common terms to describe body weight. Participants rated how much they perceived each term to be desirable, stigmatizing, blaming or motivating to lose weight (using five-point Likert scales), and how they would react if stigmatized by their doctor's reference to their weight. RESULTS: The terms 'weight' (3.43, 95% confidence interval (CI) 3.35-3.50) and 'unhealthy weight' (3.24, 95% CI 3.15 3.33) were rated most desirable, and the terms 'unhealthy weight' (3.77, 95% CI 3.69-3.84) and 'overweight' (3.51, 95% CI 3.43-3.58) were rated most motivating to lose weight. The terms 'morbidly obese', 'fat' and 'obese' were rated as the most undesirable (95% CI 1.61-2.06), stigmatizing (95% CI 3.66-4.05) and blaming (95% CI 3.62-3.94) language used by health providers. Notably, participant ratings were consistent across socio-demographic variables and body weight categories. A total of 19% of participants reported they would avoid future medical appointments and 21% would seek a new doctor if they felt stigmatized about their weight from their doctor. CONCLUSION: This study advances our understanding of why individuals prefer particular weight-related terms, and how patients may react if their provider uses stigmatizing language to refer to their weight. It also offers suggestions for practical strategies that providers can use to improve discussions about weight-related health with patients. PMID- 22777542 TI - Time-of-day and nutrient composition of eating occasions: prospective association with the metabolic syndrome in the 1946 British birth cohort. AB - BACKGROUND: Diet is a key modifiable factor in the prevention and treatment of the metabolic syndrome. However, few studies have examined the prospective association between time-of-day of nutrient intake and the metabolic syndrome. OBJECTIVE: To examine the association between time-of-day and nutrient composition of eating occasions and the long-term development of metabolic syndrome in the Medical Research Council (MRC) National Survey of Health and Development (NSHD; 1946 British birth cohort). METHODS: The analysis comprised 1488 survey members who completed at least 3 days of estimated diet records at age 43 years (1989) and for whom data on metabolic syndrome at age 53 years (1999) were available. Dietary records were divided into seven meal slots: breakfast, mid-morning, lunch, mid-afternoon, dinner, late evening and extras. Metabolic syndrome was defined by the criteria of the adult treatment panel (ATPIII8), and was modified to include glycosylated haemoglobin instead of fasting glucose. Associations between time-of-day of nutrient intake at age 43 years and prevalence of metabolic syndrome at age 53 years were assessed using multivariate nutrient density logistic models after adjustment for sex, social class, smoking status, region, alcohol intake and recreational physical activity. RESULTS: There were 390 cases of metabolic syndrome at age 53 years. Substituting 5% of energy from carbohydrate for a similar amount of energy from fat at breakfast (odds ratio=0.93; 95% confidence interval=0.89-0.98; P=0.002) and mid morning at age 43 years (odds ratio=0.96; 95% confidence interval=0.93-0.99; P=0.011) was associated with lower odds of the metabolic syndrome at age 53 years. Carbohydrate intake at breakfast or mid-morning was particularly protective against abdominal obesity (P?0.001). Increasing carbohydrate intake at breakfast while simultaneously decreasing fat intake was also negatively related to triacylglycerols (P?0.001). CONCLUSIONS: Increasing carbohydrate intake in the morning while simultaneously reducing fat intake could be protective against long term development of the metabolic syndrome and its components. PMID- 22777544 TI - Persistent effects of women's parity and breastfeeding patterns on their body mass index: results from the Million Women Study. AB - OBJECTIVE: To explore the long-term effects of women's childbearing patterns on their body mass index. DESIGN: Cross-sectional analysis. SETTING: Population based study of UK women. PARTICIPANTS: 740 628 postmenopausal participants in the Million Women Study who reported their height, weight, reproductive histories and other relevant factors. MAIN OUTCOME MEASURES: Standardized mean BMI (kg m(-2)) in groups defined by their parity and breastfeeding history. RESULTS: Women were aged 57.5 (s.d. 4) years on average, and had a mean BMI of 26.2 kg m(-2) (s.d. 5); 88% were parous, with 2.1 (s.d. 1.2) children on average. The standardised mean BMI increased progressively with the number of births from 25.6 kg m(-2) (95% confidence interval (CI): 25.5-25.6) in nulliparous women up to 27.2 kg m( 2) (CI: 27.2-27.3) for women with four or more births, a difference of 1.7 kg m( 2) (CI: 1.6-1.7). Among the parous women 70% had ever breastfed and their average total duration of breastfeeding was 7.7 (s.d. 8.8) months. At every parity level the standardised mean BMI was significantly lower among women who had breastfed than those who had not, decreasing by 0.22 kg m(-2) (CI: 0.21-0.22) for every 6 months of breastfeeding, that is, women's mean BMI was 1% lower for every 6 months that they had breastfed. These associations were highly statistically significant (P<0.0001) and independent of the effects of socioeconomic group, region of residence, smoking and physical activity. CONCLUSIONS: Childbearing patterns have a persistent effect on adiposity in this population. The reduction in BMI associated with just 6 months breastfeeding in UK women could importantly reduce their risk of obesity-related disease as they age. PMID- 22777547 TI - Safe laws on assisted dying are working worldwide. PMID- 22777548 TI - Safety of intravitreal anti-VEGFs during pregnancy is unclear. PMID- 22777546 TI - Mucosal antibodies in the regulation of tolerance and allergy to foods. AB - The intestinal mucosa is densely packed with antibody-secreting B cells, the majority of which produce IgA. Mucosal antibodies have traditionally been thought of as neutralizing antibodies that exclude antigens, but they also function in antigen sampling, allowing for selective transcytosis of antigens from the intestinal lumen. IgE-mediated antigen uptake can facilitate the development of allergic reactions to foods, but emerging evidence indicates that IgG-mediated antigen uptake may also play an important role in the development of immune tolerance to foods, particularly in the neonate. This review will focus on the role of intestinal immunoglobulins in the development of clinical tolerance and allergy to food antigens. PMID- 22777549 TI - A carefully crafted law should protect and reassure vulnerable people. PMID- 22777550 TI - Abortion reform's lessons for assisted dying. PMID- 22777545 TI - Early life precursors, epigenetics, and the development of food allergy. AB - Food allergy (FA), a major clinical and public health concern worldwide, is caused by a complex interplay of environmental exposures, genetic variants, gene environment interactions, and epigenetic alterations. This review summarizes recent advances surrounding these key factors, with a particular focus on the potential role of epigenetics in the development of FA. Epidemiologic studies have reported a number of nongenetic factors that may influence the risk of FA, such as timing of food introduction and feeding pattern, diet/nutrition, exposure to environmental tobacco smoking, prematurity and low birth weight, microbial exposure, and race/ethnicity. Current studies on the genetics of FA are mainly conducted using candidate gene approaches, which have linked more than 10 genes to the genetic susceptibility of FA. Studies on gene-environment interactions of FA are very limited. Epigenetic alteration has been proposed as one of the mechanisms to mediate the influence of early life environmental exposures and gene-environment interactions on the development of diseases later in life. The role of epigenetics in the regulation of the immune system and the epigenetic effects of some FA-associated environmental exposures are discussed in this review. There is a particular lack of large-scale prospective birth cohort studies that simultaneously assess the interrelationships of early life exposures, genetic susceptibility, epigenomic alterations, and the development of FA. The identification of these key factors and their independent and joint contributions to FA will allow us to gain important insight into the biological mechanisms by which environmental exposures and genetic susceptibility affect the risk of FA and will provide essential information to develop more effective new paradigms in the diagnosis, prevention, and management of FA. PMID- 22777551 TI - Suggested merger of mental and neurological illnesses is premature. PMID- 22777552 TI - Minding the brain. PMID- 22777553 TI - Editorial note on results of assisted dying poll. PMID- 22777554 TI - Why neutrality on assisted dying is not an option for doctors' professional organisations. PMID- 22777555 TI - My journey from anti to pro assisted dying. PMID- 22777556 TI - Imperative to track all those billions lost to avoid corruption. PMID- 22777557 TI - A one sided story. PMID- 22777559 TI - Messages associated with the Olympics are far from ideals. PMID- 22777560 TI - Legal changes are crucial to fight HIV, says new report. PMID- 22777561 TI - New EU drug safety committee ends national reporting of drug reactions. PMID- 22777562 TI - Environmental groups criticise European Commission's environmental record. PMID- 22777563 TI - Ethnic differences in ventricular hypertrabeculation on cardiac MRI in elite football players. AB - PURPOSE: Left ventricular (LV) trabeculation may be more pronounced in ethnic African than in Caucasian (European) athletes, leading to possible incorrect diagnosis of left ventricular non-compaction cardiomyopathy (LVNC). This study investigates ethnic differences in LV hypertrabeculation amongst elite athletes with cardiac magnetic resonance (CMR) and electrocardiography (ECG). METHODS: 38 elite male football (soccer) players (mean age 23.0, range 19-34 years, 28/38 European, 10/38 African) underwent CMR and ECG. Hypertrabeculation was assessed using the ratio of non-compacted to compacted myocardium (NC/C ratio) on long axis and short-axis segments. ECGs were systematically rated. RESULTS: No significant differences were seen in ventricular volumes, wall mass or E/A ratio, whereas biventricular ejection fraction (EF) was significantly lower in African athletes (European/African athletes LVEF 55/50 %, p = 0.02; RVEF 51/48 %, p = 0.05). Average NC/C ratio was greater in African athletes but only significantly at mid-ventricular level (European/African athletes: apical 0.91/1.00, p = 0.65; mid-ventricular 0.89/1.45, p < 0.05; basal 0.40/0.46, p = 0.67). ECG readings demonstrated no significant group differences, and no correlation between ECG anomalies and hypertrabeculation. CONCLUSIONS: A greater degree of LV hypertrabeculation is seen in healthy African athletes, combined with biventricular EF reduction at rest. Recognition of this phenomenon is necessary to avoid misdiagnosis of LVNC. PMID- 22777564 TI - Botulinum toxin treatment of myofascial pain: a critical review of the literature. AB - This is a review of literature relevant to the treatment of myofascial pain syndrome by botulinum injections. The objective is to critically review the studies to see if they are appropriately designed, conducted, and interpreted to provide guidance in the management of myofascial pain. The intent is to better understand the mixed results that these studies have provided. A search was made utilizing PubMed for literature relevant to the use of botulinum toxin in the treatment of myofascial pain. All identifiable series were reviewed, including open label, single-blinded and double-blinded studies, randomized and controlled, or not. In general, small case series of only a few patients were not included unless they made a relevant point and there were no available randomized studies or larger studies. Single case reports were not included. This is not a meta analysis. The studies were evaluated according to their design and the selection of outcome measurements, and the interpretation of results. The studies were individually critiqued, and an overall assessment and commentary was made of the studies in the field as a whole. Problems that were common to the studies were robust placebo responders, incomplete treatment of a regional myofascial pain syndrome, inappropriate or confounding control populations or treatments, and inappropriate time periods for assessment of outcomes, or misinterpretation of the time-frame of action of botulinum toxin. The studies of the effect of botulinum toxin treatment of myofascial trigger points have had mixed results. However, few studies have been designed to avoid many of the pitfalls associated with a trial of botulinum toxin treatment of trigger points. Better-designed studies may give results that can be used to guide practice based on reliable evidence. At the present time, one must conclude that the available evidence is insufficient to guide clinical practice. PMID- 22777565 TI - Creature comforts: personal communities, pets and the work of managing a long term condition. AB - OBJECTIVES: To explore in the context of peoples' personal social networks, the contribution that pets make to 'the work' associated with the management of long term conditions. METHOD: Mixed methods survey with nested parallel qualitative study; 300 participants were drawn from diabetes and chronic heart disease registers of General Practices across Greater Manchester in the North West of England. Notions of 'work' were used to describe the illness and everyday activities associated with chronic illness. RESULTS: Nineteen percent of participants identified at least one pet within their network. Pets contributed mostly to managing emotions (emotional work), to enhancing a sense of self identity (biographical work) and to a lesser extent practical tasks (everyday work). There were indicators that pets mediated relationships for people living with a long-term condition through very weak ties with others in domestic and community settings. CONCLUSION: The findings suggest that pets have unique qualities and are not simply substitutes for human relationships in long-term condition management. The study has potential implications for furthering a social contextual analysis of chronic illness, the understanding of relationships, and the meaning and the role of companion animals in long-term condition management. PMID- 22777566 TI - Hidden decay of impact after education for self-management of chronic illnesses: hypotheses. AB - People with chronic illnesses can benefit from self-management education. However, those benefits are said to decay over time (there is some evidence that this 'decay of impact' does occur), and the reinforcements used to prevent that decay appear to be ineffective. We hypothesize that the reinforcements appear to be ineffective because decay of impact occurs only in a subgroup of these programs' participants, so any benefits of reinforcements in that subgroup are concealed by whole-group summary statistics. We also hypothesize that reinforcements can benefit those who need them - those who would otherwise have decay. One approach to testing these hypotheses requires analysis of individual level data, which is uncommon in this field. Some useful data could come from studies that have already been completed, but the strongest evidence will require prospectively designed tests in future trials. If the hypotheses are false, then time and resources spent on reinforcements can be saved or redirected. If the hypotheses are true, then reinforcements can be implemented with less waste and they can be made more effective. These programs can also be improved to better fit their users' needs, and there can be a new basis for evaluating the programs' effectiveness. PMID- 22777567 TI - The Supreme Court and the Affordable Care Act: milestone or detour on the road to universal coverage? PMID- 22777568 TI - Cerebral microhemorrhage in Marchiafava-Bignami disease detected by susceptibility-weighted imaging. AB - Marchiafava-Bignami disease (MBD) is a rare alcohol-associated disorder. Clinical features include not only disturbed consciousness, dysarthria, tetraparesis, astasia-abasia, and symptoms of interhemispheric disconnection as initial symptoms but also cognitive deficits as clinical outcomes. The clinical significance of cerebral microhemorrhage (CMH) has been recognized in patients with cognitive deficits; however, the presence of CMH in patients with MBD has not been emphasized. The aim of the present study was to clarify the relationship between CMH and MBD. For this purpose, we report four patients with MBD, who showed asymmetrical hypointense areas in multiple cortico-subcortical regions on susceptibility-weighted imaging (SWI). All cases had a history of chronic alcohol abuse and symmetrical lesions in the entire corpus callosum. These patients' clinical symptoms included not only coma, dysarthria, and astasia-abasia as initial symptoms but also dementia as a clinical outcome. SWI showed asymmetrical hypointense areas in the multiple cortico-subcortical regions, indicating the presence of CMH. Compared with patients with normal cognitive function, demented patients showed higher severity of CMH. Our report would indicate that CMH is an important factor indicating the severity of dementia in patients with MBD. PMID- 22777569 TI - Prion-like mechanisms in epileptogenesis. AB - Epilepsy often follows a focal insult, and develops with a time delay so to reveal a complex cascade of events. Both clinical and experimental findings suggest that the initial insult triggers a self-promoted pathological process, currently named epileptogenesis. An early phase reflects the complex response of the nervous system to the insult, which includes pro-injury and pro-repair mechanisms. Successively, the sprouting and probably neurogenesis and gliosis set up the stage for the onset of spontaneous seizures. Thus, local changes in excitability would cause a functional change within a network, and the altered circuitry would favor the seizures. A latent or clinically silent period, as long as years, may precede epilepsy. In spite of the substantial knowledge on the biochemical and morphological changes associated with epileptogenesis, the mechanisms supposedly underlying the process are still uncertain. The uncertainty refers mostly to the silent period, a stage in which most, if not all, the receptor and ion changes are supposedly settled. It is tempting to explore the nature of the factors promoting the epileptogenesis within the notional field of neurodegeneration. Specifically, several observations converge to support the hypothesis that a prion-like mechanism promotes the "maturation" process underlying epileptogenesis. The mechanism, consistently with data from different neurodegenerative diseases, is predictably associated with deposition of self aggregating misfolded proteins and changes of the ubiquitin proteasome and autophagy-lysosome pathways. PMID- 22777570 TI - Current status of trends in ischemic and hemorrhagic strokes. PMID- 22777571 TI - Structural and molecular analysis of pollution-linked deformities in a natural Aphanius fasciatus (Valenciennes, 1821) population from the Tunisian coast. AB - The Eastern coast of Tunisia hosts a mosaic of populations of the Mediterranean killifish A. fasciatus, an excellent monitoring species for the analysis of environmental impact in coastal Mediterranean areas. Among these populations, fish from the Sfax area, in the Gulf of Gabes, are known for presenting a high prevalence of different physiological alterations, including spinal deformation. Compared to a reference clean area, Luza, Sfax water and sediments are polluted with heavy metals (20 to 40 times more Cd, for example) and other compounds like PAHs (10 times higher levels). Histological analyses of deformed fish from this area showed an abnormal abundance of collagen fibers infiltrated in the spinal area, either as a physiological mechanism to alleviate the consequences of the deformation of the bones or as a secondary effect of the same pathological/toxicity mechanism inducing bone deformation. Deformed fish from Sfax showed elevated (4-5 fold) levels of transcripts from the collagen COL1A2 gene in bone tissue, compared to either non-deformed animals from the same location or normal animals from the reference Luza site. These results are consistent with an overexpression of collagen in the bone tissue, in agreement with the histological results. We propose that the deformation observed in the Sfax Aphanius population is a degenerative process occurring in adult animals and probably terminal, as it results in severe limitations on the fish capacity to swim, to catch food, and ultimately to survive. PMID- 22777572 TI - Improving patients' quality of life at the end of life: comment on "factors important to patients' quality of life at the end of life". PMID- 22777573 TI - Inhibition of neovascularization but not fibrosis with the fluocinolone acetonide implant in autosomal dominant neovascular inflammatory vitreoretinopathy. AB - OBJECTIVE To review the effect of the fluocinolone acetonide implant in subjects with autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), an inherited autoimmune uveitis. METHODS A retrospective case series was assembled from patients with ADNIV who received fluocinolone acetonide implants. Visual acuity and features of ADNIV, including inflammatory cells, neovascularization, fibrosis, and cystoid macular edema, were reviewed. RESULTS Nine eyes of 5 related patients with ADNIV with uncontrolled inflammation were reviewed. Follow up ranged from 21.7 to 56.7 months. Visual acuity at implantation ranged from 20/40 to hand motion. Preoperatively, 8 eyes had vitreous cells (a ninth had diffuse vitreous hemorrhage). Eight eyes had cystoid macular edema, 7 had an epiretinal membrane, and 3 had retinal neovascularization. Following implantation, vitreous cells resolved in all eyes and neovascularization regressed or failed to develop. Central macular thickness improved in 4 eyes. During the postoperative course, however, visual acuity continued to deteriorate, with visual acuity at the most recent examination ranging from 20/60 to no light perception. There was also progressive intraocular fibrosis and phthisis in 1 case. Four eyes underwent cataract surgery. Six of the 7 eyes without previous glaucoma surgery had elevated intraocular pressure at some point, and 3 of these required glaucoma surgery. CONCLUSIONS The fluocinolone acetonide implant may inhibit specific features of ADNIV such as inflammatory cells and neovascularization but does not stabilize long-term vision, retinal thickening, or fibrosis. All eyes in this series required cataract extraction, and more than half required surgical intervention for glaucoma. Further studies may identify additional therapies and any benefit of earlier implantation. PMID- 22777574 TI - Development of a disease-specific quality-of-life questionnaire for anterior and central skull base pathology--the skull base inventory. AB - OBJECTIVES/HYPOTHESIS: Anterior and central skull base lesions and their surgical treatment (endoscopic or open approaches) can affect quality of life. A disease specific instrument is needed to compare quality of life for different surgical approaches. STUDY DESIGN: Items were generated using a composite strategy consisting of chart review, systematic review of skull base instruments, expert interviews, and qualitative analysis of patient focus groups. A cross-sectional survey study was performed to reduce items based on an item impact score. METHODS: Charts of 138 patients who underwent skull base surgery were reviewed to identify physical items and domains. Five experts were interviewed for item and domain identification. Thirty-four patients were recruited into eight focus groups based on their surgical approach (open or endoscopic) and tumor location (anterior or central). Items were generated using a composite approach and then reduced into a final questionnaire using item impact scores. RESULTS: Chart review identified 47 physical items. Systematic review revealed nine relevant instruments with 217 relevant items. Experts identified 11 domains with 69 additional items. Qualitative analysis of focus groups generated 49 items. A total of 382 items were identified and reduced to 77 items after eliminating overlapping and irrelevant items. Further item reduction using item impact scores yielded 41 items. CONCLUSIONS: The Skull Base Inventory is a disease-specific quality-of-life instrument. Psychometric properties have yet to be tested. It may serve to compare quality of life for endoscopic or open procedures. PMID- 22777575 TI - Development and characterization of a novel nystatin-loaded nanoemulsion for the buccal treatment of candidosis: ultrastructural effects and release studies. AB - Oral candidosis is a common opportunistic infection in patients suffering from mucositis (after chemotherapy and radiotherapy administration) and must be treated to prevent infecting other tissue. Nystatin (Nys) is one of the most prescribed drugs to treat this pathology, but because of its physicochemical properties, its pharmaceutical-technological requirements make it a challenge. The purpose of this work was the development and characterization of an optimal Nys delivery system for the potential treatment of oral candidosis avoiding undesirable side effects and toxicity of potential systemic absorption. A nanoemulsion was developed, evaluated, and characterized. It has been formulated successfully as a stable nanoemulsion with a droplet size of 138 nm. Release parameters were estimated using different mathematical approaches, and from the results of ex vivo permeation study of Nys through porcine buccal mucosa, it could be hypothesized that no systemic effects would happen. Microbiologic studies performed revealed an enhanced antifungal effect of the Nys-loaded nanoemulsion. Also, the evaluation of the treated buccal mucosa ultrastructure by transmission electron microscopy revealed a harmless effect. Thus, it could be inferred that the developed formulation could be potentially utilized for candidosis infection under mucositis conditions. PMID- 22777576 TI - Down-staging (= -1 cm. Secondary outcome measures included overall prolapse stage, subjective reporting of satisfaction, and any healing abnormalities or complications resulting from suture type. RESULTS: A total of 230 patients were reviewed (80 in group 1 and 150 in group 2) and median follow-up was 52 (24-174) weeks. A statistically significant improvement in anterior wall anatomy was seen in group 1 compared to group 2 [(Aa -2.70 +/- 0.6 cm vs -2.5 +/- 0.75 cm, p = 0.02) and Ba (-2.68 +/- 0.65 cm vs -2.51 +/- 0.73 cm, p = 0.03), respectively]. Comparing prolapse stage, there were no observed differences between the groups. Exposure of the permanent suture occurred in 12 patients (15 %) and 5 (6.5 %) required suture trimming to treat the exposure. CONCLUSIONS: Reattachment of endopelvic fascia to the apex at the time of anterior colporrhaphy results in low recurrence rates. Use of permanent suture for apical fixation is associated with improved anatomic correction at the expense of increased suture exposures. PMID- 22777584 TI - Comment on Forsgren et al.: Anal incontinence and bowel dysfunction after sacrocolpopexy for vaginal vault prolapse. PMID- 22777586 TI - Development of novel cell lines of diabetic dysfunction model fit for cell-based screening tests of medicinal materials. AB - Pdx-1 and Irs-1, genes highly associated with diabetes onset, were knocked down in mouse embryonic stem (ES) cells in order to develop cell line models for diabetes. ES cells with different gene knockdown levels were induced to differentiate to the stage of insulin production. Among the cell lines that differentiated, we identified two in which the levels of expression of both genes were 20-40 % of that of control cells. These cell lines showed appreciable deficiencies in three characteristic malfunctions associated with diabetes, namely, insulin production, insulin reception signaling, and glucose-stimulated insulin secretion. These dysfunctions were consistent with results reported elsewhere from in vivo and in vitro studies. Both cell lines did not show any abnormal morphology such as size, shape, color, and surface roughness. No abnormal expression profiles for 17 genes relevant to diabetes were observed. Therefore, these cell lines fulfilled the criteria for a validated cell model for diabetes. The model cell lines developed here are promising biomaterials for cell based screening tests of new medicines that may be effective in treating diabetes. PMID- 22777587 TI - Report of breakout session: Defining parameters for correcting the acetabulum during a pelvic reorientation osteotomy. PMID- 22777588 TI - Parafoveal chondral defects associated with femoroacetabular impingement. AB - BACKGROUND: Cam-type, pincer, and mixed femoroacetabular impingement (FAI) are accepted causes of labral and acetabular rim injury; however, the abnormal contact stresses associated with motion may damage other areas of the hip. Although cartilage damage to the femoral head has been reported previously in athletes, FAI-associated focal parafoveal chondral defects differ from previously reported lesions and represent a rare manifestation of the complex pathomechanics associated with FAI. QUESTIONS/PURPOSES: We describe the clinical, radiographic, and surgical characteristics of a rare focal anterolateral parafoveal femoral chondral defect associated with FAI. METHODS: We retrospectively reviewed 10 patients with symptomatic FAI diagnosed with this unique focal defect confirmed at the time of surgical dislocation. Patients presented with hip pain, clinical findings of FAI, and, frequently, with an identifiable lesion on MRI arthrography. The minimum clinical followup was 12 months (mean, 29 months; range, 12-72 months). RESULTS: The consistent characteristics of these lesions associated with FAI differ from previously reported femoral chondral damage reported after hip dislocation or lateral impact in that there was no discrete injury such as a fall or dislocation/subluxation, no associated traumatic femoral lesion, and all were localized to the posterosuperior femoral head. Eight of 10 were diagnosed preoperatively using MR arthrography. CONCLUSIONS: Despite radiographic similarities to findings of osteoarthritis and osteonecrosis, these FAI-associated femoral chondral defects were amenable to surgical reconstruction using first- or second-generation cartilage repair techniques during surgical treatment of impingement. The etiology of these lesions may be related to complex intraarticular forces generated by FAI-associated transient hip subluxation or forceful nonconcentric motion. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22777589 TI - Acetabular component positioning using anatomic landmarks of the acetabulum. AB - BACKGROUND: The acetabular cup should be properly oriented to prevent dislocation and to reduce wear. However, achieving proper cup placement is challenging with potentially large variations of cup position. We propose a new technique to position the acetabular cup. QUESTIONS/PURPOSES: We used this technique, then determined actual cup position and subsequent dislocation rate. METHODS: We measured acetabular abduction (alpha degrees ) and anteversion (beta degrees ) on preoperative CT scans in 46 patients (50 hips) scheduled for THA. During the operation, we identified the transverse acetabular notch (TAN) and anterior acetabular notch (AAN), a notch at the anterior acetabular margin. We then marked two reference points for 40 degrees abduction at the acetabular rim: the superior point, which is opposite the TAN, and the inferior point at |alpha - 40| mm inside (when alpha was > 40 degrees ) or outside the TAN (when alpha was < 40 degrees ). We also marked two reference points for 15 degrees anteversion: the posterior point opposite the AAN and the anterior point at |beta - 15| mm inside (when beta was < 15 degrees ) or outside the AAN (when beta was > 15 degrees ). During cup insertion, we aligned cup abduction to the line between the superior and inferior points and cup anteversion to the line between the anterior and posterior points. We measured cup abduction and anteversion and evaluated the dislocation rate. One patient was lost to followup before 60 months; the minimum followup for the other 45 patients was 60 months (mean, 62.8 months; range, 60-65 months). RESULTS: The mean cup abduction was 40 degrees (range, 32 degrees -47 degrees ) and the mean cup anteversion was 17 degrees (range, 8 degrees -25 degrees ). No dislocation occurred postoperatively in 49 hips (45 patients) for a minimum of 5 years followup. CONCLUSIONS: We obtained adequate cup position with our method and none of 45 patients (49 hips) had dislocation. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of level of evidence. PMID- 22777590 TI - Complex ankle arthrodesis using the Ilizarov method yields high rate of fusion. AB - BACKGROUND: Ankle arthrodesis may be achieved using the Ilizarov method. Comorbidities, such as diabetes, Charcot neuroarthropathy, osteomyelitis, leg length discrepancy, and smoking, can make an ankle fusion complex and may be associated with lower rates of healing. QUESTIONS/PURPOSES: We asked if (1) smoking and other comorbidities led to lower fusion rates, (2) time wearing the frame affected outcome, and (3) simultaneous tibial lengthening improved fusion rates. METHODS: We retrospectively studied 101 patients who underwent complex ankle fusion using the Ilizarov technique. The median time wearing the frame was 25 weeks (range, 10-65 weeks). Twenty-four patients had simultaneous tibial lengthening. The minimum followup for 91 of the 101 patients was 27 months (median, 65 months; range, 27-134 months). RESULTS: Fusion was achieved in 76 of 91 patients. Smoking was associated with a 54% rate of nonunion. Fifteen of 19 patients with Charcot neuroarthropathy achieved union but had a high rate of subsequent subtalar joint failure. Time wearing the frame did not affect union rates. Tibial lengthening did not improve ankle fusion rates. CONCLUSION: Smokers should be warned of the high risk of nonunion and we recommend they quit smoking. We also recommend surgeons recognize the higher nonunion rate in patients with Charcot neuroarthropathy. We believe tibial lengthening should not be performed to enhance healing at the fusion site. LEVEL OF EVIDENCE: Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 22777591 TI - Acquiring transgenic tobacco plants with insect resistance and glyphosate tolerance by fusion gene transformation. AB - The advantages of gene 'stacking' or 'pyramiding' are obvious in genetically modified (GM) crops, and several different multi-transgene-stacking methods are available. Using linker peptides for multiple gene transformation is considered to be a good method to meet a variety of needs. In our experiment, the Bt cry1Ah gene, which encodes the insect-resistance protein, and the mG ( 2 ) -epsps gene, which encodes the glyphosate-tolerance protein, were connected by a 2A or LP4/2A linker. Linker 2A is a peptide from the foot-and-mouth disease virus (FMDV) that has self-cleavage activity. LP4 is a peptide from Raphanus sativus seeds that has a recognition site and is cleaved by a protease. LP4/2A is a hybrid peptide that contains the first 9 amino acids of LP4 and 20 amino acids from 2A. We used the linker peptide to construct four coordinated expression vectors: pHAG, pHLAG, pGAH and pGLAH. Two single gene expression vectors, pSAh and pSmG(2), were used as controls. The six expression vectors and the pCAMBIA2301 vector were transferred into tobacco by Agrobacterium tumefaciens-mediated transformation, and 529 transformants were obtained. Molecular detection and bioassay detection data demonstrated that the transgenic tobaccos possessed good pest resistance and glyphosate tolerance. The two genes in the fusion vector were expressed simultaneously. The plants with the genes linked by the LP4/2A peptide showed better pest resistance and glyphosate tolerance than the plants with the genes linked by 2A. The expression level of the two genes linked by LP4/2A was not significantly different from the single gene vector. Key message The expression level of the two genes linked by LP4/2A was higher than those linked by 2A and was not significantly different from the single gene vector. PMID- 22777592 TI - Effectiveness of vaginal tablets containing lactobacilli versus pH tablets on vaginal health and inflammatory cytokines: a randomized, double-blind study. AB - The purpose of this study was to evaluate the effectiveness of lactobacilli on vaginal health and proinflammatory cytokines. Sixty-seven patients with bacterial vaginosis (BV), 50 with intermediate flora and 42 with normal vaginal flora were enrolled in this double-blind study. The subjects were randomized to receive probiotic lactobacilli vaginal tablets (L. brevis CD2, L. salivarius subsp. salicinius, L. plantarum) or the vaginal pH tablet (active comparator). Cervico vaginal lavage was collected to measure the concentrations of IL-1beta, TNFalpha and IL-6 by ELISA. Neutral sphingomyelinase activity was also quantified in both arms before and after treatment. The probiotic vaginal tablet was well tolerated and no side effects were reported. The study demonstrated a cure rate of nearly 80 %; i.e., 32 % of the women could restore normal vaginal flora and 47 % had improved Nugent score, whereas 20 % of the subjects did not clear BV in the first follow-up (after 8 days treatment). The pH tablet containing pH lowering compounds induced resolution of BV and restoration of normal vaginal flora in 74 % and 26 %, respectively. The lactobacilli tablet was found to be better than the pH tablet in preventing BV in healthy subjects. A significant reduction in IL 1beta and IL-6 vaginal cytokines was observed after treatment with lactobacilli, while the active comparator did not have any effect on local proinflammatory cytokines. Vaginal neutral sphingomyelinase activity was not modified in either group. Vaginal tablets containing lactobacilli can cure BV and reduce vaginal inflammatory response. PMID- 22777593 TI - Detection of phase I IgG antibodies to Coxiella burnetii with EIA as a screening test for blood donations. AB - The presence of a high phase I IgG antibody titre may indicate chronic infection and a risk for the transmission of Coxiella burnetii through blood transfusion. The outbreak of Q fever in the Netherlands allowed for the comparison of an enzyme immunoassay (EIA) with the reference immunofluorescence assay (IFA) in a large group of individuals one year after acute Q fever. EIA is 100 % sensitive in detecting high (>=1:1,024) phase I IgG antibody titres. The cost of screening with EIA and confirming all EIA-positive results with IFA is much lower than screening all donations with IFA. This should be taken into account in cost effectiveness analyses of screening programmes. PMID- 22777594 TI - Phage therapy to control multidrug-resistant Pseudomonas aeruginosa skin infections: in vitro and ex vivo experiments. AB - The main goal of this study was to evaluate the efficiency of phage therapy against one of the most common multidrug-resistant (MDR) agents of skin infections, Pseudomonas aeruginosa. A phage suspension [10(8) plaque-forming units (PFU) mL(-1)] was obtained using the clinical strain P. aeruginosa 709 as the host. The ability of the phage to inactivate P. aeruginosa was evaluated in vitro and ex vivo (human skin), using a multiplicity of infection (MOI) of 0.5 to 50. In the presence of the phage, the density of P. aeruginosa 709 [10(5) colony forming units (CFU) mL(-1)] in the human skin decreased by 4 logs after 2 h of incubation. The application of a second dose of phage did not increase the efficiency of the therapy. This study indicates that the topical application of phage PA709 efficiently inactivates MDR P. aeruginosa 709. The high efficiency in the inactivation of MDR P. aeruginosa 709, its considerable host range (infection of 30 % of the P. aeruginosa isolates) and its high stability in buffer and ex vivo human skin make this phage very promising for the treatment of P. aeruginosa skin infections. The phage-bacteria interactions were examined in vitro and in ex vivo in order to provide a basis for the selection of the most suitable protocol for subsequent in vivo experiments. PMID- 22777595 TI - Characterisation of occupational exposure to air contaminants in a nitrate fertiliser production plant. AB - The aim of this study was to characterise personal exposures to dust, acid vapours, and gases among workers in a Norwegian nitrate fertiliser production plant, as part of an ongoing epidemiological study. In total, 178 inhalable and 179 thoracic aerosol mass fraction samples were collected from randomly chosen workers (N = 141) from three compound fertiliser departments (A, B and C), a calcium nitrate fertiliser production department, nitric acid- and ammonia production departments, and a shipping department. The overall median inhalable and thoracic aerosol mass concentrations were generally low (1.1 mg m(-3) (min max: <0.93-45) and 0.21 mg m(-3) (min-max: <0.085-11), respectively). Workers at the compound fertiliser departments B and C had significantly higher inhalable aerosol mass air concentrations compared to the other departments (p < 0.05), except for compound fertiliser department A; however, the difference between the compound fertiliser department C and calcium nitrate department was slightly above the significant level. Workers at the compound fertiliser department A had significantly higher thoracic aerosol mass air concentrations compared to the other departments (p < 0.05), except for compound fertiliser departments B and C. The results indicate that the extrathoracic aerosol fraction of the aerosol compared to the thoracic fraction dominated in most departments. Measurement of the main constituents Ca, K, Mg, and P in the water-soluble and water-insoluble aerosol mass fractions showed that the air concentrations of these elements were low. There is, however, a shift towards more water-soluble species as the production goes from raw material with phosphate rock towards the final product of fertilisers. Overall, the arithmetic mean of water-soluble Ca in the thoracic mass fraction was 51% (min-max: 1-100). A total of 169 personal samples were analysed for HNO(3) vapour and HF. The highest median concentration of HNO(3) (0.63 mg m(-3)) was in the compound fertiliser departments B, and all measurements but four of the HF concentrations were below the LOD of 190 MUg m( 3). Exposures to NH(3), CO and NO(2) were measured using direct-reading electrochemical sensors and the time weighted overall averages were all below the LODs of the respective sensors, NH(3) 2 ppm; CO 2 ppm; and NO(2) 0.2 ppm, but some short-term peaks were detected. Even though our results indicate that the workers may experience peak exposure episodes when performing job tasks such as cleaning or maintenance work, the overall air concentrations are well below what is considered to cause known health risks. PMID- 22777596 TI - Seizures in acute stroke: incidence, risk factors and prognosis. AB - BACKGROUND AND PURPOSE: Studies on post-stroke seizures have produced conflicting results. Our study aim was to further elucidate the incidence and predictive factors of early post-stroke seizures (ES) and their relationship with outcome. METHODS: relevant clinical data were prospectively collected in 2,053 patients with acute stroke admitted to the Stroke Unit from 2004 to 2008. RESULTS: Sixty six patients (8 hemorrhagic and 58 ischemic strokes) aged 73-88 years (mean age 82 years) presented seizures in the first week after stroke onset. The type of ischemic stroke was atherothrombotic in 10 patients, cardioembolic in 21, lacunar in 4, undetermined in 19, and of other etiology in 4. Twenty-seven patients had generalized convulsive, 6 had complex partial, and 33 had simple partial seizures. Status epilepticus was observed in 13 patients. The severity of strokes in patients with ES was greater than in those without (National Institutes of Health Stroke Scale >14 in 50 vs. 25%), so mortality (30 days) was higher (29 vs. 14%). Independent seizure predictors were: total anterior circulation infarct, hemorrhagic transformation, hyperglycemia, and the interaction term diabetes * hyperglycemia. CONCLUSIONS: ES may be considered a marker of stroke severity. Cortical location of the lesion, hemorrhagic transformation, and hyperglycemia in patients without diabetes are important predictors of ES. PMID- 22777597 TI - Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma. AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumors with poor prognosis due to extremely high malignancy, low rate of eligibility for surgical resection and chemoradiation resistance. Increasing evidence indicate that the interaction between activated pancreatic stellate cells (PSCs) and PDAC cells plays an important role in the development of PDAC. By producing high levels of cytokines, chemotactic factors, growth factors and excessive extracellular matrix (ECM), PSCs create desmoplasia and a hypoxic microenvironment that promote the initiation, development, evasion of immune surveillance, invasion, metastasis and resistance to chemoradiation of PDAC. Therefore, targeting the interaction between PSCs and PDAC cells may represent a novel therapeutic approach to advanced PDAC, especially therapies that target PSCs of the pancreatic tumor microenvironment. PMID- 22777598 TI - Improving quality of care at the end of life. PMID- 22777599 TI - A contrast stretching bilateral closing top-hat Otsu threshold technique for crack detection in images. AB - Detection of cracks from stainless steel pipe images is done using contrast stretching technique. The technique is based on an image filter technique through mathematical morphology that can expose the cracks. The cracks are highlighted and noise removal is done efficiently while still retaining the edges. An automated crack detection system with a camera platform has been successfully implemented. We compare crack extraction in terms of quality measures with those of Otsu's threshold technique and the another technique (Iyer and Sinha, 2005). The algorithm shown is able to achieve good results and perform better than these other techniques. PMID- 22777600 TI - Chondrogenic progenitor cells respond to cartilage injury. AB - OBJECTIVE: Hypocellularity resulting from chondrocyte death in the aftermath of mechanical injury is thought to contribute to posttraumatic osteoarthritis. However, we observed that nonviable areas in cartilage injured by blunt impact were repopulated within 7-14 days by cells that appeared to migrate from the surrounding matrix. The aim of this study was to assess our hypothesis that the migrating cell population included chondrogenic progenitor cells that were drawn to injured cartilage by alarmins. METHODS: Osteochondral explants obtained from mature cattle were injured by blunt impact or scratching, resulting in localized chondrocyte death. Injured sites were serially imaged by confocal microscopy, and migrating cells were evaluated for chondrogenic progenitor characteristics. Chemotaxis assays were used to measure the responses to chemokines, injury conditioned medium, dead cell debris, and high mobility group box chromosomal protein 1 (HMGB-1). RESULTS: Migrating cells were highly clonogenic and multipotent and expressed markers associated with chondrogenic progenitor cells. Compared with chondrocytes, these cells overexpressed genes involved in proliferation and migration and underexpressed cartilage matrix genes. They were more active than chondrocytes in chemotaxis assays and responded to cell lysates, conditioned medium, and HMGB-1. Glycyrrhizin, a chelator of HMGB-1 and a blocking antibody to receptor for advanced glycation end products (RAGE), inhibited responses to cell debris and conditioned medium and reduced the numbers of migrating cells on injured explants. CONCLUSION: Injuries that caused chondrocyte death stimulated the emergence and homing of chondrogenic progenitor cells, in part via HMGB-1 release and RAGE-mediated chemotaxis. Their repopulation of the matrix could promote the repair of chondral damage that might otherwise contribute to progressive cartilage loss. PMID- 22777601 TI - Facial nerve hemangioma: a rare case involving the vertical segment. AB - This case report and literature review reports on a rare case of facial nerve hemangioma (FNH) involving the vertical facial nerve (FN) segment, and discusses the clinical presentation, imaging, pathogenesis, and management of these rare lesions. A 53-year-old male presented with a 10-year history of right hemifacial twitching and progressive facial paresis (House-Brackmann grading score V/VI). The computed tomography and magnetic resonance imaging studies confirmed an expansile lesion along the vertical FN segment. Excision and histopathologic examination demonstrated FNH. FNHs involving the vertical FN segment are extremely rare. Despite being rare lesions, we believe that familiarity with the presentation and management of FNHs are imperative. Laryngoscope, 2012. PMID- 22777603 TI - Sedentary behaviour and life expectancy in the USA: a cause-deleted life table analysis. AB - OBJECTIVES: To determine the impact of sitting and television viewing on life expectancy in the USA. DESIGN: Prevalence-based cause-deleted life table analysis. SETTING: Summary RRs of all-cause mortality associated with sitting and television viewing were obtained from a meta-analysis of available prospective cohort studies. Prevalences of sitting and television viewing were obtained from the US National Health and Nutrition Examination Survey. PRIMARY OUTCOME MEASURE: Life expectancy at birth. RESULTS: The estimated gains in life expectancy in the US population were 2.00 years for reducing excessive sitting to <3 h/day and a gain of 1.38 years from reducing excessive television viewing to <2 h/day. The lower and upper limits from a sensitivity analysis that involved simultaneously varying the estimates of RR (using the upper and lower bounds of the 95% CI) and the prevalence of television viewing (+/-20%) were 1.39 and 2.69 years for sitting and 0.48 and 2.51 years for television viewing, respectively. CONCLUSION: Reducing sedentary behaviours such as sitting and television viewing may have the potential to increase life expectancy in the USA. PMID- 22777602 TI - Changes in grey matter development in autism spectrum disorder. AB - Results on grey matter (GM) structural alterations in autism spectrum disorder (ASD) are inconclusive. Moreover, little is known about age effects on brain structure abnormalities in ASD beyond childhood. Here, we aimed to examine regional GM volumes in a large sample of children, adolescents, and adults with ASD. Magnetic resonance imaging scans were obtained in 47 male ASD subjects and 51 matched healthy controls aged 8-50 years. We used whole-brain voxel-based morphometry to first assess group differences in regional GM volume across age. Moreover, taking a cross-sectional approach, group differences in age effects on regional GM volume were investigated. Compared to controls, ASD subjects showed reduced GM volumes in the anterior cingulate cortex, posterior superior temporal sulcus, and middle temporal gyrus. Investigation of group differences in age effects on regional GM volume revealed complex, region-specific alterations in ASD. While GM volumes in the amygdala, temporoparietal junction, septal nucleus and middle cingulate cortex increased in a negative quadratic fashion in both groups, data indicated that GM volume curves in ASD subjects were shifted to the left along the age axis. Moreover, while GM volume in the right precentral gyrus decreased linearly with age in ASD individuals, GM volume development in controls followed a U-shaped pattern. Based on a large sample, our voxel-based morphometry results on group differences in regional GM volumes help to resolve inconclusive findings from previous studies in ASD. Results on age-related changes of regional GM volumes suggest that ASD is characterized by complex alterations in lifetime trajectories of several brain regions that underpin social-cognitive and motor functions. PMID- 22777604 TI - The development of an assessment and intervention falls guide for older hospitalized adults with cardiac conditions. AB - BACKGROUND: Older patients with chronic cardiac conditions are more vulnerable to falls and injuries. Cardiovascular conditions, prevalent in older people, are also the frequent cause of potentially harmful fall injuries among this group. The need to identify the fall risk-related factors that cluster with arrhythmia and syncope is relevant as it will potentially reduce patients' risk for falls and fall injuries. AIM: The paper describes the process taken to design, develop and implement a practice-change initiative that specifically focuses on cardiac related falls and injuries. PROCESS: A review of best practice guidelines, related studies and patients' profiles from chart audits were utilized to obtain evidence-based information to develop this assessment and intervention falls guide. Prior to the development of this guide, the charts of six patients were reviewed to assess specific data including age, history of falls, type of injury, cognitive function and underlying medical conditions. The developed Assessment and intervention falls guide was utilized with seven patients in the Cardiology Unit who were admitted with diagnosis of syncope and atrial fibrillation to assess their risk for falls. CONCLUSION: The project demonstrated an evidence informed process that was used to design and implement this assessment tool and a change in nursing practice. It also provided information about the prevalence of cardiac-related risk fall factors that were utilized in the development of this Assessment and Intervention Falls Guide for elderly people. PMID- 22777605 TI - Bilateral simultaneous-onset nongranulomatous acute anterior uveitis: clinical presentation and etiology. AB - OBJECTIVE To describe the etiology and outcome of patients with simultaneous onset nongranulomatous bilateral acute anterior uveitis. METHODS The medical records of patients who presented to a single tertiary care center with simultaneous-onset nongranulomatous bilateral acute anterior uveitis between January 1990 and May 2010 were retrospectively reviewed; the clinical presentation, results of diagnostic testing, and outcome data are described. RESULTS A total of 4288 new patients with uveitis were evaluated by the Uveitis Service at the University of Illinois at Chicago Eye and Ear Infirmary between January 1990 and May 2010. Of these new patients, 44 (1%) presented with simultaneous-onset nongranulomatous bilateral acute anterior uveitis. The most common etiologies were postinfectious or drug-induced uveitis (23 of 44 patients [52%]) and idiopathic uveitis (15 patients [34%]). Tubulointerstitial nephritis and uveitis syndrome, HLA-B27-associated uveitis, inflammatory bowel disease, and Kawasaki disease each made up fewer than 5% of diagnoses. Overall, this group of patients was younger than the entire cohort of new patients with uveitis who were evaluated during the same time period (P = .002). For 14 of the 15 patients with at least a year of follow-up (93%), the disease duration was limited (<3 months). Of these 14 patients, 7 (50%) developed recurrent disease, with an average time to first recurrence of 20 months (range, 7.5-40 months) after resolution of the initial inflammatory episode. CONCLUSIONS Simultaneous-onset nongranulomatous bilateral acute anterior uveitis is a rare clinical entity that is more common in younger patients and is most frequently associated with recent infection and/or systemic antibiotic use. Tubulointerstitial nephritis and uveitis syndrome should also be considered as a diagnosis. Diagnostic evaluation should include serum antistreptolysin-O titers, HLA-B27 antigen, and urine beta2 microglobulin levels because these may reveal systemic disease that requires therapy. PMID- 22777607 TI - Accelerated blood clearance of pegylated liposomal topotecan: influence of polyethylene glycol grafting density and animal species. AB - Upon repeated administration, empty pegylated liposomes lose long-circulating characteristics, referred to as accelerated blood clearance (ABC) phenomenon. However, pegylated liposomal cytotoxic drug formulations could not elicit the phenomenon. In the study, it was found that repeated injection of pegylated liposomal topotecan could induce ABC phenomenon in Wistar rats, beagle dogs, and mice, which might be associated with the formation of empty liposomes in circulation because of the rapid drug release rate. In rats, the 9% polyethylene glycol (PEG) formulation induced more severe ABC phenomenon than 3% PEG formulation despite the similar anti-PEG immunoglobulin M (IgM) levels following the first dose. Antibody neutralization experiments revealed that high PEG formulation was easily neutralized by IgM. Repeated administration of 3% PEG formulation in dogs could result in more severe ABC phenomenon. It seems that slow infusion was liable to cause ABC phenomenon. In all animal species, considerable intraindividual variability of IgM levels could be observed. Our observations may have important implications for the development, evaluation, and therapeutic use of pegylated liposomal cytotoxic drug formulations because using the current drug loading technology, most of the cytotoxic drugs could not be stably loaded in liposomes and rapid drug leakage from liposomes might occur in circulation. PMID- 22777608 TI - Erratum to: Genetic services and testing in Brazil. AB - Brazil is a continent-size country with around 190 million inhabitants, the largest and most populous in South America. It is classified as a developing upper middle-income country and having considerable growth, although inequality remains significant. The health system is mixed; most of the population is served by the public Unified Health System ("Sistema Unico de Saude", SUS) and there is a thriving private health sector. The country faces multiple obstacles to improve and expand genetic services, due to its wide territory, sociocultural inequalities and major basic health problems. Most comprehensive genetic services are concentrated in large urban centers in the South and Southeast regions, mainly in tertiary care university hospitals. Demand for genetic services has increased and congenital malformations has been the second cause of infant mortality since 2000, but such data did not determine government policies or initiatives for the prevention and management of this group of problems until 2004, when the process for introducing medical genetics as a health policy by the Ministry of Health began. Details on the policy and an overview on congenital and genetic diseases, the state and availability of genetic services, genetic testing, medical genetics laboratories, training of human resources in medical genetics, newborn screening program, genetics networks, special care facilities, as well as educational, social and support programs for disabled people, research priorities in genetics and genomics, patient organizations and relevant issues regarding the challenge of implementing a comprehensive care policy in clinical genetics in this vast and diverse country are presented. PMID- 22777609 TI - Dioxin/POPs legacy of pesticide production in Hamburg: part 1--securing of the production area. AB - alpha-Hexachlorocyclohexane (HCH), beta-HCH, and gamma-HCH (lindane) were recently included as new persistent organic pollutants (POPs) in the Stockholm Convention. Therefore, the chemicals need to be globally addressed, including the disposal of historic wastes. At most sites, the approximately 85% of HCH waste isomers were dumped. At a former lindane factory in Hamburg and some other factories the HCH, waste was recycled producing residues with high polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/PCDF) levels. The soil and ground water under the former pesticide factory was/is highly contaminated with HCH (260 tons), chlorobenzenes (550 tons), and PCDD/PCDF (6 kg toxic equivalents (TEQ)). This contamination did not result from disposal operations but from spillages and leakages during the 30 years of the factory's production history. A containment wall has been constructed around the production area to prevent the dispersal of the pollutants. The ground water is managed by a pump and treat system. Over the last 15 years, approximately 10-30 tons of this pollution reservoir has been pumped and incinerated. For the contaminated production buildings, specific assessment and demolition technologies have been applied. In addition to their HCH waste isomer deposition, former lindane/HCH productions need to be assessed for possible recycling practice of HCH and related PCDD/PCDF contamination of the production area and buildings. Since such recycling activities have taken place at several factories in different countries, the experience of assessment and management of the described production area and contaminated buildings could be valuable. Such assessment could be addressed within the frame of the Stockholm Convention. PMID- 22777610 TI - Airborne black carbon concentrations over an urban region in western India temporal variability, effects of meteorology, and source regions. AB - This study characterizes over 5 years of high time resolution (5 min), airborne black carbon (BC) concentrations (July 2003 to December 2008) measured over Ahmedabad, an urban region in western India. The data were used to obtain different time averages of BC concentrations, and these averages were then used to assess the diurnal, seasonal, and annual variability of BC over the study region. Assessment of diurnal variations revealed a strong association between BC concentrations and vehicular traffic. Peaks in BC concentration were co-incident with the morning (0730 to 0830, LST) and late evening (1930 to 2030, LST) rush hour traffic. Additionally, diurnal variability in BC concentrations during major festivals (Diwali and Dushera during the months of October/November) revealed an increase in BC concentrations due to fireworks displays. Maximum half hourly BC concentrations during the festival days were as high as 79.8 MUg m(-3). However, the high concentrations rapidly decayed suggesting that local meteorology during the festive season was favorable for aerosol dispersion. A multiple linear regression (MLR) model with BC as the dependent variable and meteorological parameters as independent variables was fitted. The variability in temperature, humidity, wind speed, and wind direction accounted for about 49% of the variability in measured BC concentrations. Conditional probability function (CPF) analysis was used to identify the geographical location of local source regions contributing to the effective BC measured (at 880 nm) at the receptor site. The east north-east (ENE) direction to the receptor was identified as a major source region. National highway (NH8) and two coal-fired thermal power stations (at Gandhinagar and Sabarmati) were located in the identified direction, suggesting that local traffic and power plant emissions were likely contributors to the measured BC. PMID- 22777611 TI - The dioxin/POPs legacy of pesticide production in Hamburg: part 2--waste deposits and remediation of Georgswerder landfill. AB - alpha-HCH, beta-HCH, and gamma-HCH (lindane) were listed as persistent organic pollutants in the Stockholm Convention. Therefore, they need to be globally addressed including the wastes remaining from historic use and production. While at most lindane production sites the unintentionally produced 85% HCH waste isomers have been deposited, at a former pesticide factory in Hamburg-Moorfleet HCH waste isomers have been recycled from 1953 to 1984 by thermal decomposition to chlorobenzenes and resulted in high polychlorinated dibenzo-p dioxin/polychlorinated dibenzofuran (PCDD/PCDF)-contaminated residues. The management of the PCDD/PCDF-contaminated waste from the former pesticide factory in Hamburg has been assessed and quantified. Based on past accredited PCDD/PCDF measurements, the registered 3,700 tonnes of disposed thermal HCH decomposition residue contained 333 to 854 kg of PCDD/PCDF toxicity equivalent (I-TEQ) in 53 102 tonnes total sum of PCDD/PCDF. The wastes have been deposited together with other wastes in landfills in Hamburg and other parts of Germany. For the Georgswerder landfill (Hamburg), where approximately 50% of the PCDD/PCDF is disposed, current and previous situation and remediation activities are described. While PCDD/PCDF leaching from the landfill is controlled and incinerated, more water soluble organochlorines (vinyl chloride, cis-1,2 dichlorethene, chlorobenzenes) and benzene remain as a challenge for groundwater management. A comprehensive aftercare program has been established and will need to be operated by future generations including renewal of containment systems. Former lindane/HCH productions need-in addition to HCH deposits-to be assessed for possible recycling practice of HCH and related PCDD/PCDF-containing deposits. This could systematically be addressed within the Stockholm Convention implementation. PMID- 22777612 TI - Inhibitors of 5alpha-reductase-related side effects in patients seeking medical care for sexual dysfunction. AB - BACKGROUND: Despite their efficacy in the treatment of benign prostatic hyperplasia (BPH) the popularity of inhibitors of 5alpha-reductase (5ARI) is limited by their association with adverse sexual side effects. However, the real impact of 5ARI on sex hormones and sexual function is controversial. AIM: To investigate the role of 5ARI therapy on hormonal parameters and sexual function in men already complaining of sexual problems. MATERIALS AND METHODS: A consecutive series of 3837 men (mean age 63.5+/-12.8 yr) attending our outpatient clinic for sexual dysfunction was retrospectively studied. Several clinical, biochemical, and instrumental (penile color doppler ultrasound) factors were evaluated. RESULTS: Among the patients studied, 78.7% reported erectile dysfunction, 51.1% hypoactive sexual desire (HSD), 86.7% perceived reduced sleep related erections (PR-SRE) and 19.1% premature ejaculation. The use of 5ARI was associated with an increased risk of HSD and PR-SR whereas no relationship was found with erectile dysfunction and ejaculation disturbances. Subjects using 5ARI also more frequently had gynecomastia along with reduced SHBG and higher calculated free testosterone levels. All these associations were confirmed in a case-control study comparing 5ARI users with age-body mass index-smoking status and total testosterone-matched controls. CONCLUSIONS: Our data indicates that use of 5ARI in men with sexual dysfunction does not significantly exacerbate pre existing ejaculatory or erectile difficulties, but can further impair their sexual life by reducing sexual drive and spontaneous erection. PMID- 22777613 TI - Multiple sclerosis: a disease of affluence?. AB - BACKGROUND: Multiple sclerosis is rare in tropical areas, but quite common in developed countries. Hence, latitude has been accepted as a causal factor for prevalence of multiple sclerosis. However, developed countries have also strong economic power, which may be measured by real gross domestic product per capita. METHODS: Bivariate and multivariate regression models were used to assess the association of the prevalence of multiple sclerosis of 62 countries with real gross domestic product per capita and latitude. RESULTS: Real gross domestic product per capita and latitude are positively associated with the prevalence of multiple sclerosis. Real gross domestic product per capita is a much stronger predictor of prevalence of multiple sclerosis than latitude. CONCLUSION: The strong correlation between the real gross domestic product per capita and the prevalence rates of multiple sclerosis is pointing to a new direction in research on the causes of multiple sclerosis. It is plausible that certain lifestyles and consumption behaviors that require high purchasing power might be associated with an increased risk of multiple sclerosis. PMID- 22777614 TI - Factors predisposing metastatic tumor antigen 1 overexpression in hepatitis B virus associated hepatocellular carcinoma. AB - BACKGROUND/AIM: Overexpression of metastatic tumor antigen-1 (MTA-1) is suggested to be associated with frequent postoperative recurrence and poor survival of hepatocellular carcinoma (HCC) patients. In this study, we intended to determine clinical factors predisposing the overexpression of MTA-1 in patients with hepatitis B virus (HBV)-associated HCC and also examine whether MTA-1 overexpression affects the survival periods of these patients treated with curative surgical resection. METHODS: A total of 303 patients with HBV-associated HCC who underwent curative surgical resection were subjected. The expressions of MTA-1 in HCC and surrounding non-tumor liver tissues were evaluated using the immunohistochemical method. The clinical, radiological and histological characteristics of the patients were analyzed in relation to the expression of MTA-1 to find predisposing factors of MTA-1 overexpression. RESULTS: MTA-1 was overexpressed in 104 HCC tissues (34.3 %) and none of the surrounding non-tumor tissues. Clinically, MTA-1 overexpression was significantly associated with younger age, female gender, higher serum alpha-fetoprotein level, and Child Turcotte-Pugh class A. Also, portal vein thrombosis, microvascular invasion, capsular invasion and poorly histological differentiation were associated with overexpression of MTA-1. The cumulative survival rates were significantly lower in patients with MTA-1 overexpression compared with those in the MTA-1 negative group (P = 0.03). In addition to the overexpression of MTA-1, the presence of microvascular or capsular invasion was a significant factor determining the poor survival of the patients with HBV-associated HCC after curative resection. CONCLUSIONS: MTA-1 is overexpressed in patients with HBV-associated HCC of invasive nature. MTA-1 overexpression is associated with shorter survival periods of patients with HBV-associated HCC after curative resection. PMID- 22777615 TI - Hepatic injury due to combined choline-deprivation and thioacetamide administration: an experimental approach to liver diseases. AB - BACKGROUND: The induction of prolonged choline-deprivation (CD) in rats receiving thioacetamide (TAA) is an experimental approach of mild hepatotoxicity that could resemble commonly presented cases in clinical practice (in which states of malnutrition and/or alcoholism are complicated by the development of other liver associated diseases). AIM: The present study aimed to investigate the time dependent effects of a 30-, a 60- and a 90-day dietary CD and/or TAA administration on the adult rat liver histopathology and the serum markers of hepatic functional integrity. METHODS: Rats were divided into four main groups: (a) control, (b) CD, (c) TAA and (d) CD + TAA. Dietary CD was provoked through the administration of choline-deficient diet, while TAA administration was performed ad libitum through the drinking water (300 mg/l of drinking water). RESULTS: Histological examination of the CD + TAA liver sections revealed micro- and macro-vesicular steatosis with degeneration and primary fibrosis at day 30, to extensive steatosis and fibrosis at day 90. Steatosis was mostly of the macrovesicular type, involving all zones of the lobule, while inflammatory infiltrate consisted of foci of acute and chronic inflammatory cells randomly distributed in the lobule. These changes were accompanied by gradually increasing mitotic activity, as well as by a constantly high alpha-smooth muscle actin immunohistochemical staining. The determination of hepatocellular injury markers such as the serum enzyme levels' of alanine aminotransferase and aspartate aminotransferase demonstrated a decrease at day 30 (they returned to control levels at days 60 and 90). However, the determination of those serum enzymes used for the assessment of cholestatic liver injury (gamma-glutamyltransferase, alkaline phosphatase) revealed a constant (time-independent) statistically significant increase versus control values. CONCLUSIONS: Long-term combined dietary CD and TAA administration could be a more realistic experimental approach to human liver diseases involving severe steatosis, fibrosis, stellate cell activation and significant regenerative hepatocellular response. PMID- 22777616 TI - Myosin light chain kinase inhibitor inhibits dextran sulfate sodium-induced colitis in mice. AB - BACKGROUND AND AIMS: Myosin light chain kinase (MLCK) plays a central role in the mechanisms of barrier dysfunction, and intestinal epithelial MLCK protein expression is upregulated in active ulcerative colitis (UC). ML-7, a MLCK inhibitor, has been used in many MLCK studies. However, the effect of ML-7 has never been estimated in colitis models. The aim of this study was to determine whether ML-7 can treat UC. METHODS: Experimental colitis was induced and ML-7 was administered by intraperitoneal injection. The disease activity index (DAI) scores were evaluated and colon tissue was collected for the assessment of histological changes, myeloperoxidase (MPO) activity, and tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-13 and interleukin (IL)-17 levels. The small intestinal mucosa was ultrastructurally examined, epithelial MLCK protein expression and enzymatic activity were determined, and intestinal permeability was assayed using FITC-dextran 4000 (FD-4) and Evans blue (EB). RESULTS: ML-7 was found to be significantly effective in reducing the DAI scores and histological index scores, and decreasing MPO activity and TNF-alpha, IFN gamma, IL-13 and IL-17 levels. The small intestinal epithelial MLCK protein expression and enzymatic activity were downregulated by ML-7. The epithelial cells and intercellular tight junctions were ameliorated, and the amount of FD-4 in blood and EB permeating into the intestine were decreased by ML-7 in colitis mice. CONCLUSIONS: ML-7 has a significant anti-colitis effect in colitis mice. It is mainly associated with the inhibition of the epithelial MLCK protein expression, resulting in ameliorated intestinal mucosal permeability. PMID- 22777617 TI - Multimodal imaging utilising integrated MR-PET for human brain tumour assessment. AB - OBJECTIVES: The development of integrated magnetic resonance (MR)-positron emission tomography (PET) hybrid imaging opens up new horizons for imaging in neuro-oncology. In cerebral gliomas the definition of tumour extent may be difficult to ascertain using standard MR imaging (MRI) only. The differentiation of post-therapeutic scar tissue, tumour rests and tumour recurrence is challenging. The relationship to structures such as the pyramidal tract to the tumour mass influences the therapeutic neurosurgical approach. METHODS: The diagnostic information may be enriched by sophisticated MR techniques such as diffusion tensor imaging (DTI), multiple-volume proton MR spectroscopic imaging (MRSI) and functional MRI (fMRI). Metabolic imaging with PET, especially using amino acid tracers such as (18)F-fluoroethyl-L-tyrosine (FET) or (11)C-L methionine (MET) will indicate tumour extent and response to treatment. RESULTS: The new technologies comprising MR-PET hybrid systems have the advantage of providing comprehensive answers by a one-stop-job of 40-50 min. The combined approach provides data of different modalities using the same iso-centre, resulting in optimal spatial and temporal realignment. All images are acquired exactly under the same physiological conditions. CONCLUSIONS: We describe the imaging protocol in detail and provide patient examples for the different imaging modalities such as FET-PET, standard structural imaging (T1-weighted, T2 weighted, T1-weighted contrast agent enhanced), DTI, MRSI and fMRI. KEY POINTS: Hybrid MR-PET opens up new horizons in neuroimaging. Hybrid MR-PET allows brain tumour assessment in one stop. Hybrid MR-PET allows simultaneous acquisition of structural, functional and molecular images. PMID- 22777618 TI - Cardiac magnetic resonance: is phonocardiogram gating reliable in velocity encoded phase contrast imaging? AB - OBJECTIVES: To assess the diagnostic accuracy of phonocardiogram (PCG) gated velocity-encoded phase contrast magnetic resonance imaging (MRI). METHODS: Flow quantification above the aortic valve was performed in 68 patients by acquiring a retrospectively PCG- and a retrospectively ECG-gated velocity-encoded GE-sequence at 1.5 T. Peak velocity (PV), average velocity (AV), forward volume (FV), reverse volume (RV), net forward volume (NFV), as well as the regurgitant fraction (RF) were assessed for both datasets, as well as for the PCG-gated datasets after compensation for the PCG trigger delay. RESULTS: PCG-gated image acquisition was feasible in 64 patients, ECG-gated in all patients. PCG-gated flow quantification overestimated PV (Delta 3.8 +/- 14.1 cm/s; P = 0.037) and underestimated FV (Delta -4.9 +/- 15.7 ml; P = 0.015) and NFV (Delta -4.5 +/- 16.5 ml; P = 0.033) compared with ECG-gated imaging. After compensation for the PCG trigger delay, differences were only observed for PV (Delta 3.8 +/- 14.1 cm/s; P = 0.037). Wide limits of agreement between PCG- and ECG-gated flow quantification were observed for all variables (PV: -23.9 to 31.4 cm/s; AV: -4.5 to 3.9 cm/s; FV: -35.6 to 25.9 ml; RV: -8.0 to 7.2 ml; NFV: -36.8 to 27.8 ml; RF: -10.4 to 10.2 %). CONCLUSIONS: The present study demonstrates that PCG gating in its current form is not reliable enough for flow quantification based on velocity-encoded phase contrast gradient echo (GE) sequences. KEY POINTS: Phonocardiogram gating is an alternative to ECG-gating in cardiac MRI. Phonocardiogram gating shows only limited reliability for velocity-encoded cardiac MRI. Further refinements of the post-processing algorithm are necessary. PMID- 22777619 TI - (1)H MR spectroscopy with external reference solution at 1.5 T for differentiating malignant and benign breast lesions: comparison using qualitative and quantitative approaches. AB - OBJECTIVE: To compare the diagnostic capability of proton ((1)H) magnetic resonance spectroscopy (MRS) in differentiating benign from malignant breast lesions on the basis of qualitative and quantitative approaches. METHODS: We performed single-voxel (1)H MRS for 208 breast lesions, identified a clear total composite choline compounds (tCho) peak of signal-to-noise of >=2 to represent malignancy (qualitative approach), and regarded tCho concentration equal to or greater than the cut-off value to represent malignancy (quantitative approach). We compared the diagnostic ability of both approaches using the Akaike information criterion (AIC) and McFadden's R (2). RESULTS: Histologically, 169 lesions were malignant; 39 were benign. The qualitative approach demonstrated 84.6 % sensitivity and 51.3 % specificity for differentiating malignant and benign lesions. The mean tCho concentration was 1.13 mmol/kg for malignancy, 0.43 mmol/kg for benignity. The optimal cut-off point was 0.61 mmol/kg, use of which achieved 68.1 % sensitivity and 79.4 % specificity. Calculated AIC and R (2) score suggested the superiority of the quantitative approach for differentiating malignancy. CONCLUSIONS: Quantitative MRS provides higher specificity than qualitative MRS for differentiating malignant from benign lesions and could be more useful as an additional examination in routine breast MR imaging. PMID- 22777620 TI - Triple-TWIST MRA: high spatial and temporal resolution MR angiography of the entire peripheral vascular system using a time-resolved 4D MRA technique. AB - OBJECTIVES: Multi-station contrast-enhanced magnetic resonance angiography (MRA) is considered as the imaging investigation of first choice in patients suffering from peripheral arterial occlusive disease. In order to overcome venous overlay and to gain dynamic flow information as provided by digital subtraction angiography (DSA), we developed a triple injection protocol for high-resolution MRA of the entire peripheral vascular system, applying time-resolved (TR) four dimensional (4D) MRA sequences. METHODS: Ten patients underwent three-station TR MRA of the pelvis and lower extremities with DSA as reference standard. Both investigations were compared concerning stenosis on a segment-by-segment basis. Furthermore, 28 consecutive patients underwent the same MR-only imaging protocol. All images were evaluated concerning image quality (1 = non-diagnostic, 4 = excellent), venous overlay (from none up to substantial) and time to venous enhancement (very early/early/normal/late). RESULTS: Three-station TR-MRA proved feasible and was comparable with DSA in 282 vessel segments, with underestimation grade of stenosis in four segments and overestimation in four segments, respectively. In 32/38 patients no venous overlay was noted; in six patients there was mild venous overlay. Image quality was rated excellent or good in most cases. CONCLUSIONS: TR-MRA provides morphological and functional information without any timing issues due to optimal arterial enhancement at high spatial resolution without venous overlay. PMID- 22777621 TI - T2 weighted signal intensity evolution may predict pathological complete response after treatment for rectal cancer. AB - OBJECTIVES: To determine the diagnostic value of T2-weighted signal intensity evolution in the tumour for detection of complete response to neoadjuvant chemoradiotherapy in patients with rectal cancer. METHODS: Thirty-nine patients diagnosed with locally advanced adenocarcinoma and treated with chemoradiotherapy (CRT), followed by surgery, underwent magnetic resonance imaging (MRI) before and after CRT on 1.5-T MRI using T2-weighted fast spin-echo (FSE) imaging. The relative T2-weighted signal intensity (rT2wSI) distribution in the tumour and post-CRT residual tissue was characterised by means of the descriptive statistical parameters, such as the mean, 95th percentile and standard deviation (SD). Receiver operating characteristic curves were used to determine the diagnostic potential of the CRT-induced alterations (Delta) in rT2wSI descriptives. The tumour regression grade (TRG) served as a histopathological reference standard. RESULTS: CRT induced a significant decrease of approximately 50% in all rT2wSI descriptives in complete responders (TRG1). This drop was significantly larger than for incomplete response groups (TRG2-TRG4). The DeltarT2wSI descriptives produced a high diagnostic performance for identification of complete responders, e.g. Delta95th percentile, DeltaSD and Deltamean resulted in accuracy of 92%, 90% and 82%, respectively. CONCLUSIONS: Quantitative assessment of the CRT-induced changes in the tumour T2-weighted signal intensity provides high diagnostic performance for selection of complete responders. PMID- 22777622 TI - CT evaluation of coronary artery stents with iterative image reconstruction: improvements in image quality and potential for radiation dose reduction. AB - OBJECTIVES: Comparison of coronary artery stent assessment with cardiac CT angiography (cCTA) using traditional filtered back projection (FBP) and sinogram affirmed iterative reconstruction (SAFIRE), in both full- and half-radiation dose image data. METHODS: Dual-source cCTA studies of 37 implanted stents were reconstructed at full- and half-radiation dose with FBP and SAFIRE. Half-dose data were based on projections from one DSCT detector. In-stent noise, signal-to noise ratio (SNR), and stent-lumen attenuation increase ratio (SAIR) were measured and image quality graded. Stent volumes were measured to gauge severity of beam hardening artefacts. RESULTS: Full-dose SAFIRE reconstructions were superior to full-dose FBP vis-a-vis in-stent noise (21.2 +/- 6.6 vs. 35.7 +/- 17.5; P < 0.05), SNR (22.1 +/- 8.6 vs. 14.3 +/- 6.7; P < 0.05), SAIR (19.6 +/- 17.6 vs. 33.4 +/- 20.4%; P < 0.05), and image quality (4.2 +/- 0.86 vs. 3.5 +/- 1.0; P < 0.05). Stent volumes were lower measured with SAFIRE (119.9 +/- 53.7 vs. 129.8 +/- 65.0 mm(3); P > 0.05). Comparing half-dose SAFIRE with full-dose FBP, in-stent noise (26.7 +/- 13.0 vs. 35.7 +/- 17.5; P < 0.05) and SNR (18.2 +/- 6.9 vs. 14.3 +/- 6.7; P < 0.05) improved significantly. SAIR (31.6 +/- 24.3 vs. 33.4 +/- 20.4%; P > 0.05), stent volume (129.6 +/- 57.3 vs. 129.8 +/- 65.0 mm(3); P > 0.05), and image quality (3.5 +/- 1.0 vs. 3.7 +/- 1.1; P > 0.05) did not differ. Radiation dose decreased from 8.7 +/- 5.2 to 4.3 +/- 2.6 mSv. CONCLUSIONS: Iterative reconstruction significantly improves imaging of coronary artery stents by CT compared with FBP, even with half-radiation-dose data. PMID- 22777623 TI - Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study. AB - OBJECTIVE: Exercise-induced pulmonary hypertension (ePH) may represent an early, clinically relevant phase in the spectrum of pulmonary vascular disease. The purpose of this pilot study was to describe the changes in hemodynamics and exercise capacity in patients with systemic sclerosis (SSc) spectrum-associated ePH treated with open-label daily ambrisentan. METHODS: Patients were treated with ambrisentan, 5 mg or 10 mg once daily, for 24 weeks. At baseline and 24 weeks, patients with SSc spectrum disorders exercised in a supine position, on a lower extremity cycle ergometer. All patients had normal hemodynamics at rest. We defined baseline ePH as a mean pulmonary artery pressure of >30 mm Hg with maximum exercise and a transpulmonary gradient (TPG) of >15 mm Hg. The primary end point was change in pulmonary vascular resistance (PVR) with exercise. Secondary end points included an improvement from baseline in 6-minute walking distance, health-related quality of life assessments, and cardiopulmonary hemodynamics. RESULTS: Of the 12 enrolled patients, 11 completed the study. At 24 weeks there were improvements in mean exercise PVR (85.8 dynes * second/cm(5) ; P = 0.003) and mean distance covered during 6-minute walk (44.5 meters; P = 0.0007). Improvements were also observed in mean exercise cardiac output (1.4 liters/minute; P = 0.006), mean pulmonary artery pressure (-4.1 mm Hg; P = 0.02), and total pulmonary resistance (-93.0 dynes * seconds/cm(5) ; P = 0.0008). Three patients developed resting pulmonary arterial hypertension during the 24 weeks. CONCLUSION: Exercise hemodynamics and exercise capacity in patients with SSc spectrum-associated ePH improved over 24 weeks with exposure to ambrisentan. Placebo-controlled studies are needed to confirm whether this is a drug-related effect and to determine optimal therapeutic regimens for patients with ePH. PMID- 22777624 TI - Effects of chronic cortisol administration on global expression of GR and the liver transcriptome in Sparus aurata. AB - The present work was designed to assess the effects of artificially increased high plasma cortisol levels induced by slow-release cortisol implants on the mRNA abundance of the glucocorticoid receptor (GR) in different organs of Sparus aurata (Gilthead sea bream), as well as to evaluate global transcriptional changes in the liver, using the Aquagenomics S. aurata oligo-nucleotide microarray technology. For that purpose, groups of fish were intraperitoneally injected with implants containing two different concentrations of cortisol (50 or 200 MUg/g body weight). Blood and organs were sampled after 7 and 14 days of cortisol implantation. Only fish with 200 MUg/g implants exhibited a significant rise in plasma cortisol. Thus, we evaluated the expression of the GR in different organs in these fish 7 and 14 days post-implantation. GR mRNA abundance was upregulated in head kidney and heart of fish at both sampling times. In liver and muscle, GR mRNA abundance was upregulated after 14 days, whereas in gills, the GR mRNA transcript was upregulated earlier, at day 7. These results suggest that increased plasma cortisol induced by a slow-release implant of cortisol mimics the overall effects of stress and affects the expression of GR mRNA in a time- and organ-specific manner. Data obtained with the Aquagenomics S. aurata oligo nucleotide microarray allowed the identification of a total of 491 cortisol responsive transcripts and highlight the strong intensity of transcriptional modulation in liver of fish implanted with cortisol after 7 days, in contrast to that observed at day 14. Transcriptional remodeling highlighted a significant activity in carbohydrate metabolism mainly in the gluconeogenic pathway linked to downregulation of inflammatory and immune response processes in implanted fish. PMID- 22777625 TI - Bending and abrasion fatigue of common suture materials used in arthroscopic and open orthopedic surgery. AB - In orthopedic surgery, the reattachment of tendon to bone requires suture materials that have stable and durable properties to allow time for healing at the tendon-bone interface. The suture, not rigidly restrained within the anchor eyelet, is free to move during surgery and potentially after surgery with limb motion. During such movement, the suture is subjected to bending and frictional forces that can lead to fatigue-induced failure. We investigated some common contemporary commercial number-two-grade suture materials and evaluated their resistance to bending abrasion fatigue and the consequent failure. Sutures were oscillated over a stainless steel wire at low frequency under load. Number of abrasion cycles to failure, changes in suture morphology, and fatigue-failure method was recorded for each material. Suture structure had a significant effect on abrasion resistance, with braided sutures containing large numbers of fine high tenacity core filaments performing 15-20 times better than other braided suture structures. Ultra high molecular weight polyethylene (UHMWPE) core filaments resisted bending abrasion failure better than other core materials due to the load spreading and abrasion resistance of these filaments. Sutures with UHMWPE cores also had high resistance to tensile failure. Limited correlation was observed between tensile strength and abrasion resistance. PMID- 22777628 TI - Through a glass, darkly. PMID- 22777630 TI - Cranberry-containing products for prevention of urinary tract infections in susceptible populations: a systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Urinary tract infection (UTI) is one of the most commonly acquired bacterial infections. Cranberry-containing products have long been used as a folk remedy to prevent UTIs. The aims of this study were to evaluate cranberry containing products for the prevention of UTI and to examine the factors influencing their effectiveness. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systemically searched from inception to November 2011 for randomized controlled trials that compared prevention of UTIs in users of cranberry-containing products vs placebo or nonplacebo controls. There were no restrictions for language, population, or publication year. RESULTS: Thirteen trials, including 1616 subjects, were identified for qualitative synthesis from 414 potentially relevant references; 10 of these trials, including a total of 1494 subjects, were further analyzed in quantitative synthesis. The random-effects pooled risk ratio (RR) for cranberry users vs nonusers was 0.62 (95% CI, 0.49-0.80), with a moderate degree of heterogeneity (I(2) = 43%) after the exclusion of 1 outlier study. On subgroup analysis, cranberry-containing products seemed to be more effective in several subgroups, including women with recurrent UTIs (RR, 0.53; 95% CI, 0.33-0.83) (I(2) = 0%), female populations (RR, 0.49; 95% CI, 0.34-0.73) (I(2) = 34%), children (RR, 0.33; 95% CI, 0.16-0.69) (I(2) = 0%), cranberry juice drinkers (RR, 0.47; 95% CI, 0.30-0.72) (I(2) = 2%), and subjects using cranberry-containing products more than twice daily (RR, 0.58; 95% CI, 0.40-0.84) (I(2) = 18%). CONCLUSIONS: Our findings indicate that cranberry-containing products are associated with protective effect against UTIs. However, this result should be interpreted in the context of substantial heterogeneity across trials. PMID- 22777632 TI - The consequences of ineffective regulation of dietary supplements. PMID- 22777633 TI - Percutaneous coronary intervention for stable coronary artery disease: the debate continues. PMID- 22777634 TI - Stenting vs medical therapy for stable coronary artery disease: a minefield for meta-analyses? PMID- 22777636 TI - Polycyclic aromatic hydrocarbons, particulate air pollution, and cognitive decline. PMID- 22777638 TI - Electron-pair density decomposition for core-valence separable systems. AB - The electron pair density of a core-valence separable system can be decomposed into three parts: core-core, core-valence, and valence-valence. The core-core part has a Hartree-Fock like structure. The core-valence part can be written as Gamma(cv) (1,2) = gamma(c) (1,1)gamma(v) (2,2) - gamma(c) (1,2)gamma(v) (2,1) + gamma(c) (2,2)gamma(v) (1,1) - gamma(c) (2,1)gamma(v) (1,2), where only the 1 matrices from the core and valence orbitals contribute. The valence-valence part is left to be determined from the reduced frozen-core type wave function, which often contains the essential information on the electron correlation and the chemical bond. We demonstrate the analysis to the ground state of negative ion Li(-) and 2(1)Sigma(u)(+) excited state of the Li(2) molecule. PMID- 22777639 TI - Transcatheter atrial septal defect closure in a patient with paradoxical brain emboli: who should treat it and who should be treated? AB - This report presents the case of a 51-year-old female who was admitted to a local hospital because of a persistent headache. A diagnosis of multiple cerebral infarctions was thereafter made, but there was no evidence of either atherosclerosis or atrial fibrillation. The case was thought to be a cryptogenic stroke, however, Doppler ultrasonography of the lower extremities showed venous insufficiency. Transesophageal echocardiography revealed a secundum atrial septal defect (ASD) with a left to right shunt. Therefore, the final diagnosis was paradoxical brain emboli, and transcatheter ASD closure was successfully performed by cardiologists without any sequelae. PMID- 22777640 TI - Primary ciliary dyskinesia, an orphan disease. AB - Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disease, caused by specific primary structural and/or functional abnormalities of the motile cilia, in contrast with the transitory abnormalities seen in secondary ciliary dyskinesia. Disease-causing mutations in at least 16 genes have already been identified. The true incidence of PCD may be higher than currently reported, because the diagnosis is challenging and often missed. For the confirmation of PCD, both ciliary motility as well as ciliary ultrastructure must be evaluated. An early and adequate diagnosis and therapy can theoretically prevent bronchiectasis. Measurement of nasal nitric oxide has some value as a screening test but cannot be performed in young children. In the respiratory tract epithelium, impaired mucociliary clearance leads to chronic and/or recurrent upper and lower respiratory tract infections. In up to 75 % of the patients, respiratory manifestations start in the newborn period, although the diagnosis is often missed at that time. During embryogenesis, nodal cilia, which are motile cilia, determine the correct lateralization of the organs. Dysfunction of these cilia leads to random lateralization and thus situs inversus in approximately 50 % of the patients with PCD. The tail of a spermatozoon has a structure similar to that of a motile cilium. Consequently, male infertility due to immotile spermatozoa is often part of the characteristics of PCD. Given the heterogeneity and the rarity of the disorder, therapy is not evidence-based. Many treatment schedules are proposed in analogy with the treatment for cystic fibrosis. CONCLUSION: Respiratory infections, situs inversus and male infertility are typical manifestations of PCD, a rare autosomal recessive disorder. PMID- 22777641 TI - Beyond "safe sex"--can we fight adolescent pelvic inflammatory disease? AB - Pelvic inflammatory disease (PID) is a common disorder affecting sexually active adolescents. The Centers for Disease Control and Prevention (CDC) and European CDC report Chlamydia trachomatis as the most common sexually transmitted infection and one of the main etiological agents causing PID. C. trachomatis' and PID's high prevalence may be attributed to multiple factors including high-risk sexual behaviors, sensitive laboratory diagnostics (polymerase chain reaction), and the introduction of chlamydia screening programs. The pathogenesis of C. trachomatis infection is complex with recent data highlighting the role of toll like receptor 2 and four in the mediation of the inflammatory cascade. The authors review the etiology of the disease, explore its pathogenesis, and discuss a variety of strategies that may be implemented to reduce the prevalence of C. trachomatis including: (a) behavioral risk reduction, (b) effective screening of asymptomatic females, (c) targeted male screening, (d) implementation of a sensitive, rapid, self-administered point-of-care testing, and (e) development of an effective vaccine. PMID- 22777642 TI - Environmental factors association between asthma and acute bronchiolitis in young children--a perspective cohort study. AB - Acute bronchiolitis and asthma are respiratory tract diseases of childhood that are characterized by wheezing. However, the diagnosis of asthma is difficult in patients younger than 2 years. We evaluated the association between asthma or acute bronchiolitis and various risk factors in young children. This perspective cohort study included a study group of children younger than 2 years with a recorded diagnosis of acute bronchiolitis (N = 4,586) as well as a control group (N = 4,263). Children in both groups were registered between January 1, 2004 and December 31, 2004, on the Taiwan Longitudinal Health Insurance Database (2005), and each child was followed in our study until December 31, 2006, using data from the same source. Of the 8,849 children in our study, 355 experienced asthma during the 3-year follow-up period. Among these 355 asthma patients, 332 children (29.1 per 1,000 person-years, 95% CI 26.2-36.4) belonged to the acute bronchiolitis cohort and 23 children (2.0 per 1,000 person-years, 95% CI 13.3 29.9) belonged to the comparison cohort. Cox proportional hazard regression analysis showed that children with acute bronchiolitis were more likely to have asthma than the control population, after adjustment for potential confounders (adjusted hazard ratio [HR] 13.55, 95% CI 8.87-20.71). Boys with acute bronchiolitis had a higher HR for asthma than girls during the 3-year follow-up. Children with acute bronchiolitis who lived in rural areas had a 1.49 HR for asthma compared with their urban counterparts. Children living in the northern region of Taiwan had a higher HR ratio than those in other regions. Sex, urbanization, and geographic region all showed significant associations with acute bronchiolitis and asthma. Based on the asthma-free survival curves of Kaplan-Meier analysis in our study, young children with acute bronchiolitis should be monitored for 2 years to prevent them from developing asthma. This was the first study to evaluate the length of time for which acute bronchiolitis poses a risk for the development of asthma in young children. PMID- 22777643 TI - Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer. AB - New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR 132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 MUg/day) or JV-1-38 (20 MUg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1alpha, metalloproteinases (MMPs) -2 and -9, beta-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1alpha expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated beta-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer. PMID- 22777645 TI - A large-scale study of the association between biopsy results and clinical manifestations in patients with suspicion of nasopharyngeal carcinoma. AB - OBJECTIVES/HYPOTHESIS: This study investigated the association between the results of nasopharyngeal (NPX) biopsies and clinical manifestations in patients with suspected nasopharyngeal carcinoma (NPC). STUDY DESIGN: Retrospective cohort study. METHODS: Four hundred seventy-three patients with 512 NPX biopsies were enrolled. The statistical analyses were conducted to evaluate clinical significance and screening performance for suspected NPC. RESULTS: The negative rate of all NPX biopsies was 69.7% (345/495), and the majority of the noncancerous group revealed lymphoid hyperplasias (208/345, 60.3%). The three diagnostic capabilities of NPX mass, epistaxis (EPI), neck mass (NM), EPI-NM, EPI NPX mass, NM-NPX mass, and EPI-NM-NPX mass were 0.595, 0.557, 0.735, 0.609, 0.566, 0.748, and 0.600, respectively. CONCLUSIONS: Although NPX mass, EPI, and NM were significant to identify suspected NPC, the diagnostic capabilities of combining EPI, NM, and NPX were still low. A large number of noncancerous biopsy results were obtained due to lymphoid hyperplasias often being mistaken as NPC. PMID- 22777649 TI - Bipolar-to-monopolar spindle collapse in human eggs. PMID- 22777646 TI - A quantitative systems approach to identify paracrine mechanisms that locally suppress immune response to Interleukin-12 in the B16 melanoma model. AB - Interleukin-12 (IL12) enhances anti-tumor immunity when delivered to the tumor microenvironment. However, local immunoregulatory elements dampen the efficacy of IL12. The identity of these local mechanisms used by tumors to suppress immunosurveillance represents a key knowledge gap for improving tumor immunotherapy. From a systems perspective, local suppression of anti-tumor immunity is a closed-loop system - where system response is determined by an unknown combination of external inputs and local cellular cross-talk. Here, we recreated this closed-loop system in vitro and combined quantitative high content assays, in silico model-based inference, and a proteomic workflow to identify the biochemical cues responsible for immunosuppression. Following an induction period, the B16 melanoma cell model, a transplantable model for spontaneous malignant melanoma, inhibited the response of a T helper cell model to IL12. This paracrine effect was not explained by induction of apoptosis or creation of a cytokine sink, despite both mechanisms present within the co-culture assay. Tumor derived Wnt-inducible signaling protein-1 (WISP-1) was identified to exert paracrine action on immune cells by inhibiting their response to IL12. Moreover, WISP-1 was expressed in vivo following intradermal challenge with B16F10 cells and was inferred to be expressed at the tumor periphery. Collectively, the data suggest that (1) biochemical cues associated with epithelial-to-mesenchymal transition can shape anti-tumor immunity through paracrine action and (2) remnants of the immunoselective pressure associated with evolution in cancer include both sculpting of tumor antigens and expression of proteins that proactively shape anti-tumor immunity. PMID- 22777650 TI - Neglected populations: safeguarding the health of street-involved children in Ghana. AB - Ensuring the health of street-involved children is a growing public health challenge. These children are vulnerable, neglected, and rarely a priority for basic service providers and governments. Sizable populations of street-involved children are present in major urban areas worldwide and current trends in urbanization suggest these populations will grow in the coming years. Although migration offers employment and training opportunities, the health and wellbeing of children is negatively impacted by their interactions with the streets. However, systemic barriers may also prevent these children from achieving an adequate health status. The situation of street-involved children in Ghana, West Africa will be discussed. PMID- 22777651 TI - Mitochondrial J haplogroup is associated with lower blood pressure and anti oxidant status: findings in octo/nonagenarians from the BELFAST Study. AB - Mitochondria produce cellular energy but also free-radicals, which damage cells despite an array of endogenous anti-oxidants. In Northern Europe, the mitochondrial haplogroup J has been related to longevity in nonagenarians and centenarians but also with age-related disease. Hypertension is an important contributor to atherosclerotic-related diseases and its pathogenesis is associated with increased oxidative stress. In this study, we questioned whether J haplogroup octo/nonagenarians from the Belfast Elderly Longitudinal Free-living Elderly STudy (BELFAST) study showed evidence of protective blood pressure or anti-oxidant profile which might explain their longevity advantage. Briefly, in a cross-sectional study, community-living, mentally alert (Folstein >25/30), octo/nonagenarian subjects, recruited for good health, were enlisted and consented as part of the BELFAST study, for blood pressure, anthropometric measurements and blood sampling. DNA typing for mitochondrial haplotypes was carried out with measurements for enzymatic and non-enzymatic antioxidants. J haplogroup carriers showed lower systolic blood pressure and glutathione peroxidase activity (Gpx) with higher folate measurements. There was no change in urate, bilirubin, albumin or nutrition-related antioxidants-selenium or vitamins A, C and alpha and beta carotene. BELFAST study mtDNA J haplogroup octo/nonagenarians showed lower blood pressure and reduced glutathione peroxidase activity and higher folate, but no change for other antioxidants. These findings are of interest in view of mtDNA J haplogroup's association with increased age in some previous studies. PMID- 22777653 TI - Friedel-Crafts-type reactions with ureas and thioureas. AB - Despite the relatively low reactivities of urea and thiourea functional groups towards nucleophilic attack, we have found conditions in which they are useful substrates in Friedel-Crafts reactions. The Bronsted superacid, triflic acid, promotes these reactions and a mechanism is proposed involving dicationic, superelectrophilic intermediates. PMID- 22777652 TI - Western-style diet modulates contractile responses to phenylephrine differently in mesenteric arteries from senescence-accelerated prone (SAMP8) and resistant (SAMR1) mice. AB - The influence of two known cardiovascular risk factors, aging and consumption of a high-fat diet, on vascular mesenteric artery reactivity was examined in a mouse model of accelerated senescence (SAM). Five-month-old SAM prone (SAMP8) and resistant (SAMR1) female mice were fed a Western-type high-fat diet (WD; 8 weeks). Mesenteric arteries were dissected, and vascular reactivity, protein and messenger RNA expression, superoxide anion (O 2 (.-) ) and hydrogen peroxide formation were evaluated by wire myography, immunofluorescence, RT-qPCR, ethidium fluorescence and ferric-xylenol orange, respectively. Contraction to KCl and relaxation to acetylcholine remained unchanged irrespective of senescence and diet. Although similar contractions to phenylephrine were observed in SAMR1 and SAMP8, accelerated senescence was associated with decreased eNOS and nNOS and increased O 2 (.-) synthesis. Senescence-related alterations were compensated, at least partly, by the contribution of NO derived from iNOS and the enhanced endogenous antioxidant capacity of superoxide dismutase 1 to maintain vasoconstriction. Administration of a WD induced qualitatively different alterations in phenylephrine contractions of mesenteric arteries from SAMR1 and SAMP8. SAMR1 showed increased contractions partly as a result of decreased NO availability generated by decreased eNOS and nNOS and enhanced O 2 (.-) formation. In contrast, WD feeding in SAMP8 resulted in reduced contractions due to, at least in part, the increased functional participation of iNOS-derived NO. In conclusion, senescence-dependent intrinsic alterations during early stages of vascular senescence may promote vascular adaptation and predispose to further changes in response to high-fat intake, which may lead to the progression of aging-related cardiovascular disease, whereas young subjects lack the capacity for this adaptation. PMID- 22777654 TI - Clinical equipoise and risk-benefit assessment. AB - Clinical equipoise is widely regarded as an ethical requirement for the design and conduct of randomized controlled trials (RCTs). Underlying clinical equipoise is the norm that no patient should be randomized to treatment known (or believed by the expert clinical community) to be inferior to the established standard of care. This implies that patient-subjects should not be exposed to net risks in control groups of randomized trials - risks that are not compensated by the prospect of direct medical benefits from the control intervention. However, proponents of clinical equipoise have no moral objections to permitting net risks for 'nontherapeutic' research procedures employed in clinical trials. This differential assessment makes risk-benefit assessment of randomized trials incoherent. In this article, I examine critically four arguments in defense of clinical equipoise as a requirement for risk-benefit assessment. Each of these arguments fails to support clinical equipoise, leading to the conclusion that we should dispense with this principle in risk-benefit assessment of RCTs. PMID- 22777655 TI - Stroke in the very elderly: characteristics and outcome in patients aged >=85 years with a first-ever ischemic stroke. AB - BACKGROUND: Epidemiological and clinical features of very elderly patients with stroke are still uncertain. Our aim was to study the patient characteristics and outcomes in the very elderly (aged >=85 years) with a first-ever ischemic stroke in the National Acute Stroke Israeli Survey (NASIS) registry. METHODS: The NASIS registry is a nationwide prospective hospital-based study performed triennially (2004, 2007, 2010). Patients with ischemic stroke aged >=85 years were compared with those 65-84 years old regarding their baseline characteristics, stroke severity, etiology of stroke and stroke outcomes. Logistic regression analyses were used to adjust for potential confounders. Stroke severity was determined according to the National Institute of Health Stroke Scale (NIHSS) score. RESULTS: The proportion of very elderly (>=85 years) patients among the NASIS population increased from 18.3% in 2004 to 19.9% in 2007 and 24.5% in 2010 (p for trend = 0.005). The percentage of women was higher in patients aged >=85 years (p < 0.0001). Atrial fibrillation, congestive heart disease and prior disability were significantly more common, while diabetes, current smoking and dyslipidemia were less frequent in the very elderly. The very elderly presented with more severe strokes: 36.3% of the >=85-year-old patients had an NIHSS score >=11 compared with 22.0% in the younger age group (p < 0.05). CONCLUSIONS: There is an increasing proportion of very elderly subjects, mostly women, among first-ever ischemic stroke patients. Current information on age-specific aspects of stroke in the very elderly is crucial to set up successful prevention pathways and implementing well-organized stroke care for this population. PMID- 22777656 TI - Signal processing techniques for oscillatory potential extraction in the electroretinogram: automated highpass cutoff frequency estimation. AB - Oscillatory potentials (OPs) are typically isolated from the electroretinogram (ERG) via linear, time-invariant, bandpass filtering. The use of a highpass cutoff frequency that is too low results in a- and b-wave contamination of the OP signal, while a cutoff frequency that is too high removes significant OP signal energy. Two methods for automated highpass cutoff frequency estimation were developed and evaluated. An OP amplitude analysis method exploited a trend in variation of maximum OP amplitude with cutoff frequency. A second method fit a time-varying exponential model to the rising edge of the b-wave and selected a cutoff frequency based on minimizing the error between the residual ERG signal (the signal formed by subtracting the OP signal from the original ERG signal) and the exponential fit. The performance of each method was evaluated at 11 luminances (0.001-100 scot cd . s/m(2)) in ten wild-type adult mice by comparing the automated selections to expert-selected highpass cutoff frequencies. It was noted that cutoff frequency selection was not critical at the lower luminance levels, but strongly influenced the OP signal shape for higher luminances. At the highest luminance, errors between the OP amplitude and exponential model versus expert selection were -6.3 +/- 13 and -8.2 +/- 7.3 Hz, respectively. ANOVAs showed that estimations made by the OP amplitude analysis method were generally statistically indistinguishable from the expert identifications. Furthermore, both OP amplitude analysis and exponential fitting error analysis provided excellent fits to the manual selections for the four highest stimulus luminance values. PMID- 22777657 TI - Presence of store-operated Ca2+ entry in C57BL/6J mouse ventricular myocytes and its suppression by sevoflurane. AB - BACKGROUND: Store-operated Ca(2+) entry (SOCE) has been implicated in various pathological conditions of the heart including ischaemia/reperfusion and ventricular hypertrophy. This study investigated the effects of sevoflurane on SOCE. METHODS: Fluorescence imaging was performed on fluo-3- and mag-fluo-4 loaded mouse ventricular myocytes to measure the cytosolic and intraluminal sarcoplasmic reticulum (SR) Ca(2+) levels, respectively, using a confocal laser scanning microscope. Whole-cell membrane currents were recorded using the patch clamp technique. Ventricular myocytes were exposed to thapsigargin and angiotensin II to deplete SR Ca(2+) stores and thereby activate SOCE. RESULTS: The combined application of thapsigargin and angiotensin II to the Ca(2+)-free medium evoked a significant decrease in the SR Ca(2+) levels, which was followed by the elevation of cytosolic Ca(2+) and the development of cellular hypercontracture upon subsequent addition of extracellular Ca(2+). This cytosolic Ca(2+) elevation was inhibited by 2-aminoethoxydiphenyl borate but not by verapamil and KB-R7943, which indicates that SOCE was present in mouse ventricular myocytes. Sevoflurane concentration-dependently inhibited the SOCE mediated Ca(2+) overload (IC(50) of 137 MUM, which corresponds to 0.96%) with a significant reduction occurring at concentrations of >=2%. Patch-clamp experiments revealed that the SOCE current was also concentration-dependently blocked by sevoflurane (IC(50) of 144 MUM, which corresponds to 1.0%). CONCLUSIONS: Sevoflurane at concentrations of >=2% significantly inhibits the SOCE activity and prevents the resultant cellular Ca(2+) overload that leads to hypercontracture in ventricular myocytes. This inhibitory action may be involved in the cardioprotective effect of sevoflurane against Ca(2+) overload-mediated injury. PMID- 22777658 TI - Risk factors for reintubation in the post-anaesthetic care unit: a case-control study. AB - BACKGROUND: Risk factors for reintubation in post-anaesthetic care units related to anaesthetic processes have not previously been reported. Our goal was to identify risk factors for reintubation in general surgical patients. METHODS: A time-matched, case-control study was conducted on anaesthetic patients between 2001 and 2011. One hundred and sixty-four reintubated patients were compared with 656 randomly selected controls. RESULTS: Independent risk factors for reintubation were age <1 yr vs age 30-49 yr [odds ratio (OR)=16.4, 95% confidence interval (CI)=5.7-47.7], chronic pulmonary disease (OR=2.1, CI=1.1-4.0), preoperative hypoalbuminaemia (OR=4.9, CI=2.4-10), creatinine clearance <24 vs >60 (OR=4.1, CI=1.2-13.4), emergency case (OR=1.8, CI=1.0-3.1), operative time >3 vs <1 h (OR=3.0, CI=1.5-6.2), airway surgery (OR=32.2, CI=13.6-76), head and neck surgery (OR=3.4, CI=1.8-6.2), cardiac surgery (OR=3.8, CI=1.1-13.4), thoracic surgery (OR=6.3, CI=1.9-21.2), cardiac catheterization (OR=2.5, CI=1.1-5.5), ASA physical status III (OR=3.8, CI=1.4-10), and the use of certain types of neuromuscular blocking agent (P<0.001). CONCLUSIONS: Age <1 yr, chronic pulmonary disease, preoperative hypoalbuminaemia, and renal insufficiency were patient factors for reintubation. Emergency case, head and neck, cardiothoracic and airway surgery, and operative time >3 h were operative factors, while certain neuromuscular blocking agents and ASA physical status III were anaesthetic factors for reintubation. PMID- 22777659 TI - Case report: surviving a tiger attack. AB - Attacks on humans by large predators are rare, especially in Northern Europe. In cases of involvement of the craniocervical compartment, most of the attacks are not survived. We report on a case where the patient survived a tiger attack despite severe head trauma and discuss the circumstances leading to the patient's survival and excellent outcome. The patient we report on is a 28-year-old tamer, who was attacked by three tigers during an evening show. A bite to the head resulted in multiple injuries including left-sided skull penetration wounds with dislocated fractures, dural perforations, and brain parenchyma lesions. The patient recovered without neurological deficits after initial ICU treatment. No infection occurred. In order to understand the mechanism of the tiger's bite to the patient's cranium, a simulation of the attack was performed using a human and a tiger skull put together at identical positions to the bite marks in a CT scan. It seems that during the bite, the animal was not able to clamp down on the patient's skull between its canine teeth and therefore reduced bite forces were applied. Survival of an attack by a large predator that targeted the cervical cranial compartment with an excellent outcome is not described in the literature. We were surprised to find only minor lesions of the brain parenchyma despite the obvious penetration of the skull by the tiger's canines. This seems to be related to the specific dynamics of the cranial assault and the reduced forces applied to the patient's head demonstrated in a 3D bite simulation. PMID- 22777661 TI - Concomitant craniospinal injuries and whole-body CT. PMID- 22777660 TI - Long-term follow-up of ruptured intracranial aneurysms treated by microsurgical wrapping with autologous muscle. AB - The purpose of this study is to describe our series of nine unclippable and uncoilable ruptured aneurysms in eight patients treated by microsurgical wrapping with autologous muscle. Records were retrospectively reviewed for rebleeding rate, morbidity and mortality, changes in size or the aneurysm's configurations, and inflammatory reaction. We conducted a Medline search in the post microsurgical era, excluding patients in whom wrapping was part of the aneurysm treatment in combination with clipping or coiling. The surgically related morbidity was 12.5%. Global mortality rate was 25% due to vasospasm (one case) and rebleeding (one case). Six patients are still alive. Rebleeding rate was 14.3% within 6 months; then, it was zero. Glasgow outcome scale (GOS) score at discharge was 1 and 4 in one patient, respectively, and 5 in the remaining six. Mean clinical follow-up was 126 months. GOS at last follow-up was 4 and 5 in 50% of patients, respectively. Mean mRS score was 0.8 at 2 months, and 2.4 at 12 months. Follow-up MR demonstrated persistence of the aneurysm's sac, without changes in size and configuration. Patients did not describe or exhibit symptoms attributable to complications inherent to the use of muscle. Microsurgical muscle wrapping of ruptured intracranial aneurysm is safe, is associated with a low rate of acute and delayed postoperative complications and rebleeding, and could be a valid alternative for unclippable and non-amenable to endovascular procedure ruptured aneurysms. PMID- 22777662 TI - Jumbled NETs promote vasculitis. PMID- 22777663 TI - Bleeding is rarely good for you. PMID- 22777664 TI - Nonatherosclerotic arterial disorders of the lower extremities. PMID- 22777665 TI - Catheter ablation of atrial fibrillation. PMID- 22777667 TI - Multiple papillary fibroelastomas. PMID- 22777666 TI - Bridge to recovery: understanding the disconnect between clinical and biological outcomes. PMID- 22777668 TI - Massive systemic air embolism during aortic root angiography: a dire complication. PMID- 22777670 TI - Letter by Lee et al regarding article, "Spontaneous resolution of central serous chorioretinopathy in a patient with congenital retinal macrovessel". PMID- 22777671 TI - Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons. AB - The mammalian hippocampus harbours neural circuitry that is crucial for associative learning and memory. The mechanisms that underlie the development and regulation of this complex circuitry are not fully understood. Our previous study established an essential role for the zinc finger protein Zbtb20 in the specification of CA1 field identity in the developing hippocampus. Here, we show that conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired hippocampus-dependent memory formation, without affecting hippocampal architecture or the survival, identity and basal excitatory synaptic activity of CA1 pyramidal neurons. We demonstrate that mature CA1-specific Zbtb20 knockout mice exhibited reductions in long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents. Furthermore, we show that activity-induced phosphorylation of ERK and CREB is impaired in the hippocampal CA1 of Zbtb20 mutant mice. Collectively, these results indicate that Zbtb20 in mature CA1 plays an important role in LTP and memory by regulating NMDAR activity, and activation of ERK and CREB. PMID- 22777672 TI - Preinspiratory calcium rise in putative pre-Botzinger complex astrocytes. AB - The neural inspiratory activity originates from a ventrolateral medullary region called the pre-Botzinger complex (preBotC), yet the mechanism underlying respiratory rhythmogenesis is not completely understood. Recently, the role of not only neurons but astrocytes in the central respiratory control has attracted considerable attention. Here we report our discovery that an intracellular calcium rise in a subset of putative astrocytes precedes inspiratory neuronal firing in rhythmically active slices. Functional calcium imaging from hundreds of preBotC cells revealed that a subset of putative astrocytes exhibited rhythmic calcium elevations preceding inspiratory neuronal activity with a time lag of approximately 2 s. These preinspiratory putative astrocytes maintained their rhythmic activities even during the blockade of neuronal activity with tetrodotoxin, whereas the rhythm frequency was lowered and the intercellular phases of these rhythms were decoupled. In addition, optogenetic stimulation of preBotC putative astrocytes induced firing of inspiratory neurons. These findings raise the possibility that astrocytes in the preBotC are actively involved in respiratory rhythm generation in rhythmically active slices. PMID- 22777673 TI - ATP-mediated vasodilatation occurs via activation of inwardly rectifying potassium channels in humans. AB - Circulating ATP possesses unique vasomotor properties in humans and has been hypothesized to play a role in vascular control under a variety of physiological conditions. However, the primary downstream signalling mechanisms underlying ATP mediated vasodilatation remain unclear. The purpose of the present experiment was to determine whether ATP-mediated vasodilatation is independent of nitric oxide (NO) and prostaglandin (PG) synthesis and occurs primarily via the activation of Na(+)/K(+)-ATPase and inwardly rectifying potassium (K(IR)) channels in humans. In all protocols, young healthy adults were studied and forearm vascular conductance (FVC) was calculated from forearm blood flow (measured via venous occlusion plethysmography) and intra-arterial blood pressure to quantify local vasodilatation. Vasodilator responses (%FVC) during intra-arterial ATP infusions were unchanged following combined inhibition of NO and PGs (n = 8; P > 0.05) whereas the responses to KCl were greater (P < 0.05). Combined infusion of ouabain (to inhibit Na(+)/K(+)-ATPase) and barium chloride (BaCl(2); to inhibit K(IR) channels) abolished KCl-mediated vasodilatation (n = 6; %FVC = 134 +/- 13 vs. 4 +/- 5%; P < 0.05), demonstrating effective blockade of direct vascular hyperpolarization. The vasodilator responses to three different doses of ATP were inhibited on average 56 +/- 5% (n = 16) following combined ouabain plus BaCl(2) infusion. In follow-up studies, BaCl(2) alone inhibited the vasodilator responses to ATP on average 51 +/- 3% (n = 6), which was not different than that observed for combined ouabain plus BaCl(2) administration. Our novel results indicate that the primary mechanism of ATP-mediated vasodilatation is vascular hyperpolarization via activation of K(IR) channels. These observations translate in vitro findings to humans in vivo and may help explain the unique vasomotor properties of intravascular ATP in the human circulation. PMID- 22777675 TI - Functional analysis of TCF4 missense mutations that cause Pitt-Hopkins syndrome. AB - Pitt-Hopkins syndrome (PTHS) is a rare developmental disorder associated with severe mental retardation, facial abnormalities, and intermittent hyperventilation. Autosomal dominant PTHS is caused by mutations in the transcription factor 4 (TCF4) gene, whereas NRXN1 and CNTNAP2 mutations are associated with autosomal recessive PTHS. To determine the impact of missense mutations on TCF4 function, we tested a panel of PTHS-associated mutations using a range of quantitative techniques. Mutations in the basic helix-loop-helix (bHLH) domain of TCF4 alter the subnuclear localization of the mutant protein and can attenuate homo- and heterodimer formation in homogenous time-resolved fluorescence (HTRF) assays. By contrast, mutations proximal to the bHLH domain do not alter the location of TCF4 or impair heterodimer formation. In addition, we show that TCF4 can transactivate the NRXN1beta and CNTNAP2 promoters in luciferase assays. Here we find variable, context-specific deficits in the ability of the different PTHS-associated TCF4 mutants to transactivate these promoters when coexpressed with different bHLH transcription factors. These data demonstrate that PTHS-associated missense mutations can have multiple effects on the function of the protein, and suggest that TCF4 may modulate the expression of NRXN1 and CNTNAP2 thereby defining a regulatory network in PTHS. PMID- 22777674 TI - Bicarbonate-dependent chloride transport drives fluid secretion by the human airway epithelial cell line Calu-3. AB - Anion and fluid secretion are both defective in cystic fibrosis (CF); however, the transport mechanisms are not well understood. In this study, Cl(-) and HCO(3)(-) secretion was measured using genetically matched CF transmembrane conductance regulator (CFTR)-deficient and CFTR-expressing cell lines derived from the human airway epithelial cell line Calu-3. Forskolin stimulated the short circuit current (I(sc)) across voltage-clamped monolayers, and also increased the equivalent short-circuit current (I(eq)) calculated under open-circuit conditions. I(sc) was equivalent to the HCO(3)(-) net flux measured using the pH stat technique, whereas I(eq) was the sum of the Cl(-) and HCO(3)(-) net fluxes. I(eq) and HCO(3)(-) fluxes were increased by bafilomycin and ZnCl(2), suggesting that some secreted HCO(3)(-) is neutralized by parallel electrogenic H(+) secretion. I(eq) and fluid secretion were dependent on the presence of both Na(+) and HCO(3)(-). The carbonic anhydrase inhibitor acetazolamide abolished forskolin stimulation of I(eq) and HCO(3)(-) secretion, suggesting that HCO(3)(-) transport under these conditions requires catalysed synthesis of carbonic acid. Cl(-) was the predominant anion in secretions under all conditions studied and thus drives most of the fluid transport. Nevertheless, 50-70% of Cl(-) and fluid transport was bumetanide-insensitive, suggesting basolateral Cl(-) loading by a sodium potassium-chloride cotransporter 1 (NKCC1)-independent mechanism. Imposing a transepithelial HCO(3)(-) gradient across basolaterally permeabilized Calu-3 cells sustained a forskolin-stimulated current, which was sensitive to CFTR inhibitors and drastically reduced in CFTR-deficient cells. Net HCO(3)(-) secretion was increased by bilateral Cl(-) removal and therefore did not require apical Cl(-)/HCO(3)(-) exchange. The results suggest a model in which most HCO(3)(-) is recycled basolaterally by exchange with Cl(-), and the resulting HCO(3)(-)-dependent Cl(-) transport provides an osmotic driving force for fluid secretion. PMID- 22777676 TI - Correlation of hair mineral concentrations with insulin resistance in Korean males. AB - Calcium and magnesium that are associated with insulin resistance play an antagonistic role with each other in cells. This study was conducted to investigate the relationship between hair mineral concentrations and insulin resistance in Korean adult males. A total of 123 male subjects (63 patients with metabolic syndrome and 60 normal control patients) were recruited and fasting plasma glucose, total cholesterol, triglyceride, as well as HDL cholesterol levels, HOMA-IR, and hair mineral concentrations were measured. The ratio of calcium/magnesium in hair showed a significantly positive correlation with the HOMA-IR (r = 0.191, P = 0.038) and insulin (r = 0.198, P = 0.031). The result of multiple regression analysis after adjusting the age also showed a significant correlation of the Ca/Mg ratio with HOMA-IR (R2 = 0.115, P = 0.047). The hair chromium concentration was lower in the metabolic syndrome group than in the control group, and it showed a significantly negative correlation with the fasting blood glucoseand the triglyceride. The result of this study showed that insulin resistance increased as the ratio of Ca/Mg increased, or as the chromium concentration in hair decreased. PMID- 22777677 TI - Echolocation behavior of the Japanese horseshoe bat in pursuit of fluttering prey. AB - Echolocation sounds of Rhinolophus ferrumequinum nippon as they approached a fluttering moth (Goniocraspidum pryeri) were investigated using an on-board telemetry microphone (Telemike). In 40% of the successful moth-capture flights, the moth exhibited distinctive evasive flight behavior, but the bat pursued the moth by following its flight path. When the distance to the moth was approximately 3-4 m, the bats increased the duration of the pulses to 65-95 ms, which is 2-3 times longer than those during landing flight (30-40 ms). The mean of 5.8 long pulses were emitted before the final buzz phase of moth capture, without strengthening the sound pressure level. The mean duration of long pulses (79.9 +/- 7.9 ms) corresponded to three times the fluttering period of G. pryeri (26.5 * 3 = 79.5 ms). These findings indicate that the bats adjust the pulse duration to increase the number of temporal repetitions of fluttering information rather than to produce more intense sonar sounds to receive fine insect echoes. The bats exhibited Doppler-shift compensation for echoes returning from large static objects ahead, but not for echoes from target moths, even though the bats were focused on capturing the moths. Furthermore, the echoes of the Telemike recordings from target moths showed spectral glints of approximately 1-1.5 kHz caused by the fluttering of the moths but not amplitude glints because of the highly acoustical attenuation of ultrasound in the air, suggesting that spectral information may be more robust than amplitude information in echoes during moth capturing flight. PMID- 22777678 TI - Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: a case-control study, systematic review and meta-analysis. AB - Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk of a number of cancer types, however, previous studies of endometrial cancer have yielded inconclusive results. We analyzed data from the Australian National Endometrial Cancer Study (ANECS), a population-based case-control study (1,398 cases, 740 controls). We systematically reviewed all the evidence linking aspirin/NSAIDs use with endometrial cancer and conducted a meta-analysis. For ANECS, unconditional logistic regression was used to estimate odds ratios (OR) adjusting for potential confounders. For the systematic review, we searched Pubmed, Embase, Web of Science and conducted a review of citations from retrieved articles. The meta-analysis risk estimates were pooled using a random-effects model. In our case-control study, women who had ever used aspirin in the last 5 years had a significantly lower risk of endometrial cancer OR = 0.78 [95% confidence interval (CI): 0.63-0.97]. There was a significant inverse dose-response (p-trend <0.001) such that women who reported using >=2 aspirin/week had almost half the risk OR = 0.54 (0.38-0.78). No significant associations were observed between use of half-aspirin/day, non-aspirin NSAIDs or paracetamol and endometrial cancer risk. The results were similar when examined by cancer subtype. Nine studies were included in the meta-analysis. The overall pooled risk estimate for any versus no use of aspirin was 0.87 (0.79-0.96) with no evidence of heterogeneity. The pooled risk estimate for obese women (BMI >= 30 kg/m(2) ) was 0.72 (0.58-0.90) but there was no association for non-obese women. Overall these results suggest that aspirin may reduce the risk of endometrial cancer, particularly among obese women. PMID- 22777679 TI - Parabens inhibit the early phase of folliculogenesis and steroidogenesis in the ovaries of neonatal rats. AB - Parabens are widely used as anti-microbial agents in the cosmetic and pharmaceutical industries. Recently, parabens have been shown to act as xenoestrogens, a class of endocrine disruptors. In the present study, 55 female pups were given daily subcutaneous injections of methyl-, propyl-, and butyl paraben or 17beta-estradiol (E2) during neonatal Day 1-7. The ovaries were excised on postnatal Day 8, then fixed and stained with hematoxylin and eosin for histological analysis. The follicles were counted and classified as being in the primordial, early primary, or primary stages. The number of primordial follicles increased while early primary follicles decreased at the high doses of propyl- and butyl-paraben. The levels of anti-Mullerian hormone (AMH) and Foxl2 mRNA increased by propyl- and butyl-parabens whereas kit ligand/stem cell factor (KITL) expression was up regulated only by butyl-paraben. The mRNA levels of StAR and Cyp11a1 were significantly decreased after treatment with methyl-, propyl-, and butyl-parabens. Consistent with its use as a positive control, E2 regulated the expression of KITL, StAR, and Cyp11a1 genes, but surprisingly did not affect AMH and Foxl2 levels. Thus, E2 and parabens had different effects on the regulation of folliculogenic and steroidogenic genes, demonstrating the estrogenic and nonestrogenic properties of parabens in the ovary. Taken together, our data show that parabens stimulated AMH mRNA expression and consequently inhibited the early phase of folliculogenesis in the ovaries of neonatal female rat. The levels of steroidogenic enzymes, indicators of follicle differentiation, appeared to be regulated by parabens through inhibition of their transcriptional repressor, Foxl2. PMID- 22777680 TI - Minocycline toxicity: case files of the University of Massachusetts medical toxicology fellowship. PMID- 22777682 TI - A density functional theory investigation of the cobalt-mediated eta5 pentadienyl/alkyne [5+2] cycloaddition reaction: mechanistic insight and substituent effects. AB - Alkyl-substituted eta(5)-pentadienyl half-sandwich complexes of cobalt have been reported to undergo [5+2] cycloaddition reactions with alkynes to provide eta(2),eta(3)-cycloheptadienyl complexes under kinetic control. DFT studies have been used to elucidate the mechanism of the cyclization reaction as well as that of the subsequent isomerization to the final eta(5)-cycloheptadienyl product. The initial cyclization is a stepwise process of olefin decoordination/alkyne capture, C-C bond formation, olefin arm capture, and a second C-C bond formation; the initial decoordination/capture step is rate-limiting. Once the eta(2),eta(3) cycloheptadienyl complex has been formed, isomerization to eta(5) cycloheptadienyl again involves several steps: olefin decoordination, beta hydride elimination, reinsertion, and olefin coordination; also here the initial decoordination step is rate limiting. Substituents strongly affect the ease of reaction. Pentadienyl substituents in the 1- and 5-positions assist pentadienyl opening and hence accelerate the reaction, while substituents at the 3-position have a strongly retarding effect on the same step. Substituents at the alkyne (2 butyne vs. ethyne) result in much faster isomerization due to easier olefin decoordination. Paths involving triplet states do not appear to be competitive. PMID- 22777681 TI - Angiopoietin-2 inhibition using siRNA or the peptide antagonist L1-10 results in antitumor activity in human neuroblastoma. AB - PURPOSE: The angiopoietin/Tie-2 system has been identified as a key role player in tumor angiogenesis. We investigated whether angiopoietin-2 could be a promising target in human neuroblastoma. METHODS: Angiopoietin-2 down-regulation by siRNA or shRNA was evaluated in vitro in Kelly cells. Angiopoietin-2 shRNA transfected Kelly cells were tested in a chorioallantoic membrane (CAM) assay to evaluate tumor growth and microvessel density. The effects of L1-10, a peptide-Fc fusion molecule blocking angiopoietin-2/Tie-2 interaction, administered 3 times/week were assessed in a murine neuroblastoma xenograft model. RESULTS: Angiopoietin-2 down-regulation by siRNA or shRNA in Kelly cells inhibited cell proliferation and migration. In vivo growth and microvessel density of angiopoietin-2 shRNA-transfected Kelly cells in the CAM assay were reduced. Therapy of advanced tumors with L1-10 did not stop tumor progression. However, starting L1-10 treatment at the same time as neuroblastoma cell injection significantly inhibited tumor growth (vehicule: 903 +/- 160 mm(3); L1-10: 270 +/- 152 mm(3) after 26 days; P < 0.05). Microvessel density was reduced in both L1-10 treated tumors, whereas expression of angiopoietin-2 and VEGF-A did not change. CONCLUSION: This first demonstration of beneficial angiopoietin-2 inhibition in neuroblastoma offers an additional approach for future therapy strategies, especially by using L1-10 in the setting of minimal residual disease. PMID- 22777683 TI - Retail redlining in New York City: racialized access to day-to-day retail resources. AB - Racial residential segregation is associated with health inequalities in the USA, and one of the primary mechanisms is through influencing features of the neighborhood physical environment. To better understand how Black residential segregation might contribute to health risk, we examined retail redlining; the inequitable distribution of retail resources across racially distinct areas. A combination of visual and analytic methods was used to investigate whether predominantly Black census block groups in New York City had poor access to retail stores important for health. After controlling for retail demand, median household income, population density, and subway ridership, percent Black was associated with longer travel distances to various retail industries. Our findings suggest that Black neighborhoods in New York City face retail redlining. Future research is needed to determine how retail redlining may perpetuate health disparities and socioeconomic disadvantage. PMID- 22777684 TI - The severity of mental disorders is linked to interaction among candidate genes. AB - There is a considerable overlap in the manifestation of symptoms in three mental disorders namely unipolar disorder, bipolar disorder and schizophrenia. A gene coexpression network was developed based on a mutual information approach including four candidate genes (NRG1, DISC1, BDNF and COMT) along with other coexpressing genes in unipolar disorder, bipolar disorder and schizophrenia. There is a significant difference in the degree distribution of nodes between normal and bipolar disorder network and bipolar disorder network and schizophrenia network. Moreover, there is a differential direct connectivity among candidate genes in various mental disorders and between normal and mental disorders. All candidate genes are directly connected to each other in schizophrenia except one pair (NRG1-BDNF) indicating a strong role of inter-gene interactions in the manifestation of severe symptoms in this disease. DISC1 and NRG1 are key hub genes in the unipolar disorder network and the bipolar disorder network but have lost the role of hub genes in schizophrenia network, despite their significant association with schizophrenia. This study indicates that the three psychiatric diseases may not have discrete classes but three phenotypic manifestations of the same continuous disease based on severity. PMID- 22777685 TI - An inhibitor of glutathione S-transferase omega 1 that selectively targets apoptotic cells. PMID- 22777687 TI - Super-SERS-active and highly effective antimicrobial Ag nanodendrites. AB - We have developed simple and green electrochemistry to synthesize Ag nanostructures with high purity, good crystallinity and smooth surface for applications as super-SERS (surface-enhanced Raman scattering), SERS-active substrates and with highly effective antimicrobial activities. This synthesis takes place in a clean and slow reaction environment without any chemical additives, which ensures an ultrahigh active surface of the as-synthesized Ag nanostructures owing to their purity, good crystallinity and smooth morphology. Using this method, we synthesized nearly perfect Ag nanodendrites (NDs), which exhibit super-SERS sensitivity when they are used to detect the SERS spectra of rhodamine 6G at concentrations as low as 5 * 10(-16) M, and have an ultrahigh electromagnetic (EM) enhancement factor of the order of 10(13), breaking through the theoretical limit of EM enhancement. Meanwhile, the as-synthesized Ag NDs possess highly effective antimicrobial activities for Escherichia coli, Candida albicans and Staphylococcus aureus, which are over 10 times that of silver nanoparticles. Additionally, the basic physics and chemistry involved in the fabrication of Ag nanostructures are pursued. These investigations show that silver nanostructures with highly active surfaces can make the most of Ag nanostructures functioning as super-SERS-active substrates and multiple antibiotics. PMID- 22777686 TI - Antibody nanoparticle dispersions formed with mixtures of crowding molecules retain activity and in vivo bioavailability. AB - Monoclonal antibodies continue to command a large market for treatment of a variety of diseases. In many cases, the doses required for therapeutic efficacy are large, limiting options for antibody delivery and administration. We report a novel formulation strategy based on dispersions of antibody nanoclusters that allows for subcutaneous injection of highly concentrated antibody (~ 190 mg/mL). A solution of monoclonal antibody 1B7 was rapidly frozen and lyophilized using a novel spiral-wound in-situ freezing technology to generate amorphous particles. Upon gentle stirring, a translucent dispersion of approximately 430 nm protein clusters with low apparent viscosity (~ 24 cp) formed rapidly in buffer containing the pharmaceutically acceptable crowding agents such as trehalose, polyethylene glycol, and n-methyl-2-pyrrolidone. Upon in vitro dilution of the dispersion, the nanoclusters rapidly reverted to monomeric protein with full activity, as monitored by dynamic light scattering and antigen binding. When administered to mice as an intravenous solution, subcutaneous solution, or subcutaneous dispersion at similar (4.6-7.3 mg/kg) or ultra-high dosages (51.6 mg/kg), the distribution and elimination kinetics were within error and the protein retained full activity. Overall, this method of generating high concentration, low-viscosity dispersions of antibody nanoclusters could lead to improved administration and patient compliance, providing new opportunities for the biotechnology industry. PMID- 22777688 TI - Parvovirus B19 in pregnancy: possible consequences of vertical transmission. AB - OBJECTIVE: The aim was to determine the outcome of pregnancies complicated by maternal Parvovirus B19 (B19) infection. METHOD: Among 175 pregnant women referred to our clinic because of suspicion of a B19 infection, 63 with confirmed laboratory diagnosis of acute/recent B19 infection were followed up by ultrasound and Doppler measurement of the middle cerebral artery peak systolic velocity. RESULTS: The vertical transmission rate was 31.7% (20/63). Of the 20 infected, 8 had hydrops, 1 had signs suggestive of meconium peritonitis and 1 had an isolated hydrothorax. Three fetuses presenting with hydrops were treated with intrauterine blood transfusion. Two of them died while the last showed resolution of anemia. Among the five untreated hydropic fetuses, one presented with mild signs that resolved spontaneously, two died at 16 and 17 weeks of gestation and two had also cardiomegaly and the parents opted for elective termination of pregnancy. All the anemic fetuses had middle cerebral artery peak systolic velocity values more than 1.8 multiples of the median. No stillbirth occurred. CONCLUSIONS: The outcome of uncomplicated cases with B19 infection is good. In the presence of hydrops prognosis was very poor. It seems therefore logical to attempt to pick up this ominous signs early. PMID- 22777689 TI - The toxicokinetics cell demography model to explain metal kinetics in terrestrial invertebrates. AB - Metal toxicokinetics in invertebrates are usually described by one-compartment first-order kinetic model. Although the model gives an adequate description of the toxicokinetics in certain cases, it has been shown to fail in some situations. It also does not seem acceptable on purely theoretical grounds as accumulation and excretion rates may change depending on instantaneous toxicant concentration in the gut. We postulate that the mechanism behind such changes is connected with the toxic effect of metals on gut epithelial cells. Based on published data, we have constructed a mechanistic model assuming a dynamic rate of replacement of epithelial cells with increasing contamination. We use a population-type modeling, with a population of gut epithelial cells characterized by specific death and birth rates, which may change depending on the metal concentration in food. The model shows that the equilibrium concentration of a toxicant in an organism is the net result of gut cell death and replacement rates. At low constant toxicant concentrations in food, the model predicts that toxicant-driven cell mortality is moderate and the total amount of toxicant in the intestine increases slowly up to the level resulting from the gradual increase of the cell replacement rate. At high constant concentration, total toxicant amount in the gut increases very fast, what is accompanied by massive cell death. The increased cell death rate results in reduced toxicant absorption, which in turn brings its body load down. The resulting pattern of toxicokinetic trajectory for high metal concentration closely resemble that found in empirical studies, indicating that the model probably describes the actual phenomenon. PMID- 22777690 TI - A prospective case-control study of extralevator abdominoperineal excision (ELAPE) of the rectum versus conventional laparoscopic and open abdominoperineal excision: comparative analysis of short-term outcomes and quality of life. AB - BACKGROUND: Conventional abdominoperineal excision (APE) of the rectum is associated with higher circumferential resection margin (CRM) involvement, increased local recurrence, and reduced survival compared to anterior resection. A more radical extralevator APE (ELAPE) technique may improve oncological outcome. However, this technique may confer additional morbidity, and little comparative data on short-term outcomes have been reported. This study compares short-term outcomes and quality of life (QOL) after open and laparoscopic ELAPE, laparoscopic APE (LAPE), and open APE (OAPE). METHODS: Data on all ELAPE and 10 consecutive LAPE and OAPE were extracted from a prospective database. Perioperative care and follow-up were standardized. QOL was assessed using EORTC questionnaires. RESULTS: Sixteen ELAPE (14 laparoscopic), 10 LAPE, and 10 OAPE were included. Demographics, tumour stage, and neoadjuvant therapy use were comparable. Operative time was higher with ELAPE than LAPE and OAPE (295, 207.5, and 157.5 min, respectively, p = 0.01). A porcine collagen perineal mesh was used in 9 patients undergoing ELAPE but in no LAPE or OAPE patients. No difference in 30-day complications, re-admission, or length of stay was noted. ELAPE and LAPE were associated with earlier removal of urinary catheter (p = 0.02), yet other enhanced recovery after surgery (ERAS) parameters were equivalent. All ELAPE resections were R0 with no positive CRM identified. One LAPE and 2 OAPE were R1 resections. Analysis revealed no deterioration in QOL with ELAPE, with equivalent global health status. CONCLUSIONS: The results of this study suggest that ELAPE is not associated with deterioration in short-term outcomes or QOL when compared with LAPE or OAPE. PMID- 22777691 TI - Appropriate use criteria: what's next? PMID- 22777692 TI - Increased vessel depiction of the carotid bifurcation with a specialized 16 channel phased array coil at 3T. AB - The purpose of this work was to design and construct a multichannel receive-only radiofrequency coil for 3T magnetic resonance imaging of the human carotid artery and bifurcation with optimized signal-to-noise ratio (SNR) in the carotid vessels along the full extent of the neck. A neck phantom designed to match the anatomy of a subject with a neck representing the body habitus often seen in subjects with carotid arterial disease was constructed. Sixteen circular coil elements were arranged on a semirigid fiberglass former that closely fit the shape of the phantom, resulting in a 16-channel bilateral phased array coil. Comparisons were made between this coil and a typical 4-channel carotid coil in a study of 10 carotid vessels in five healthy volunteers. The 16-channel carotid coil showed a 73% average improvement in SNR at the carotid bifurcation. This coil also maintained an SNR greater than the peak SNR of the 4-channel coil over a vessel length of 10 cm. The resulting increase in SNR improved vessel depiction of the carotid arteries over an extended field of view, and demonstrated better image quality for higher parallel imaging reduction factors compared to the 4-channel coil. PMID- 22777694 TI - Middle ear carcinoid with distant osseous metastasis. AB - Middle ear carcinoid is a rare entity with an indolent clinical course. Numerous reports have described local recurrence and metastasis to the cervical lymph nodes, although only one report of distant visceral metastasis exists in the literature. We describe the potential for osseous metastasis. A 52-year-old male with previous middle ear carcinoid (resected 10 years prior) presented with a neck mass. Subsequent workup revealed a suspicious lytic lesion of the iliac crest. Selective neck dissection and core biopsy of the iliac lesion were performed, which revealed concurrent histologically identical metastasis to both the cervical lymph nodes and iliac crest, morphologically indistinguishable from the previous middle ear carcinoid. This case presents the novel description of distant osseous metastasis of middle ear carcinoid. PMID- 22777695 TI - Adherence to national guidelines for gastric cancer in the Netherlands: a retrospective population-based audit. AB - In May 2009, a new clinical practice guideline for gastric cancer was released in the Netherlands. To determine the impact of this guideline, we evaluated trends in patterns of care, thereby focusing on the use of perioperative chemotherapy, the adequacy of lymphadenectomy and the proportion of non-curative resections. For our evaluation, we retrospectively collected information from the Netherlands Cancer Registry on 2,511 patients diagnosed with primary adenocarcinoma of the stomach during the period July 2008-June 2010, excluding tumors of the cardia. After comparing clinical management for patients diagnosed from July 2008 to June 2009 with that for patients diagnosed from July 2009 to June 2010, we conclude that our indicators for guideline adherence did not show major change, except for the proportion of patients that received an adequate lymphadenectomy (examination of >=10 lymph nodes), which increased from 49% to 58% (p = 0.005), this increase being more pronounced for high-volume hospitals (p = 0.006). Preoperative chemotherapy was given in 45% of patients and 25% of resections was non-curative. For the total study population, the resection rate was 41% and 30-day mortality was 5.7%. However, this measure may underestimate the real operative risk for gastric cancer patients given supplementary information on postdischarge death and prolonged hospital stay. PMID- 22777700 TI - Effects of Hoechst 33342 staining and ultraviolet irradiation on mitochondrial distribution and DNA copy number in porcine oocytes and preimplantation embryos. AB - Hoechst 33342 (H342), in combination with ultraviolet (UV) irradiation, is frequently used to aid or confirm the enucleation of porcine oocytes in somatic cell nuclear transfer programs. The exposure of oocytes to H342 and UV irradiation has a deleterious effect on the development of in vitro-fertilized porcine oocytes, with increasing exposure to UV irradiation (up to 30 sec) having more drastic effects. It has been hypothesized that this decrease in embryonic development could be due to damage to the mitochondrial DNA (mtDNA). To investigate this hypothesis, we analyzed the mitochondrial distribution and DNA copy number of in vitro-matured porcine oocytes exposed to H342/UV and the subsequent embryonic development compared with the mitochondrial distribution and DNA copy number of in vivo-derived oocytes and embryos. Using quantitative, real time polymerase chain reaction (qPCR) protocols to analyze mtDNA and confocal laser scanning microscopy with MitoTracker Deep Red to determine mitochondrial distribution, we demonstrated that the simultaneous exposure of in vitro-matured porcine oocytes to H342 staining and UV irradiation is associated with reduced oocyte developmental competence and abnormal mitochondrial distribution in the resulting cleaved embryos. In addition, 2- to 4-cell embryos derived from oocytes exposed to H342/UV showed a significant decrease in mtDNA copy number. These results should be considered when H342/UV procedure is used during nuclear transfer in recipient porcine oocytes. PMID- 22777693 TI - Use of support vector machines for disease risk prediction in genome-wide association studies: concerns and opportunities. AB - The success of genome-wide association studies (GWAS) in deciphering the genetic architecture of complex diseases has fueled the expectations whether the individual risk can also be quantified based on the genetic architecture. So far, disease risk prediction based on top-validated single-nucleotide polymorphisms (SNPs) showed little predictive value. Here, we applied a support vector machine (SVM) to Parkinson disease (PD) and type 1 diabetes (T1D), to show that apart from magnitude of effect size of risk variants, heritability of the disease also plays an important role in disease risk prediction. Furthermore, we performed a simulation study to show the role of uncommon (frequency 1-5%) as well as rare variants (frequency <1%) in disease etiology of complex diseases. Using a cross validation model, we were able to achieve predictions with an area under the receiver operating characteristic curve (AUC) of ~0.88 for T1D, highlighting the strong heritable component (~90%). This is in contrast to PD, where we were unable to achieve a satisfactory prediction (AUC ~0.56; heritability ~38%). Our simulations showed that simultaneous inclusion of uncommon and rare variants in GWAS would eventually lead to feasible disease risk prediction for complex diseases such as PD. The used software is available at http://www.ra.cs.uni tuebingen.de/software/MACLEAPS/. PMID- 22777701 TI - Differences of larval development and pathological changes in permissive and nonpermissive rodent hosts for Angiostrongylus cantonensis infection. AB - Angiostrongylus cantonensis is a neurotrophic and pulmonary parasite which causes severe neuropathological damages by invading and developing in the central nervous system (CNS). Nonpermissive host with A. cantonensis infection appeared to have more serious neurologic symptoms, and there is still not much knowledge about the host-parasite interrelationship in different hosts. We investigated and compared the larval size, recovery rate, distribution, and the severity of pathologic injuries in the CNS of both permissive host (e.g., rats) and nonpermissive hosts (e.g., mice). In present study, mice infected with A. cantonensis showed higher worm recovery rate in late-stage infection and smaller size of intracranial larvae as compared to the infected rats. Intracranial larvae mainly aggregated on cerebral surface of infected rats but on surface of cerebellum and brainstem in mice. Hemorrhage and tissue edema on brain surface caused by worm migration appeared earlier and severer in infected mice than in rats. Neuropathological examination revealed that injuries induced by A. cantonensis in brain parenchyma included hemorrhage, vascular dilatation, focal necrosis with neuronal loss, and infiltration of inflammatory cells. In the comparison of these pathological changes in rats and mice, infected mice suffered more serious injuries and provoked more intense inflammatory response as compared to infected rats. All these morphological evidences indicate that larval development was retardant in the CNS of nonpermissive host, and nonpermissive host experienced more serious pathological injuries than permissive host. It implies that the difference in innate immune response to parasite infection attribute to host specificity. PMID- 22777702 TI - Cuticular structures on antennae of the bot fly, Portschinskia magnifica (Diptera: Oestridae). AB - Portschinskia magnifica Pleske, 1926, is an endangered subcutaneous parasitic fly of voles that mimics bumblebees in appearance. Although the importance of antennae in Diptera has been repeatedly stressed, there is still a lack of morphology information of this group, let alone this species. Antennae of adult P. magnifica were studied with a stereoscopic microscope and scanning electron microscope. Six subtypes of antennal sensilla were observed on the funiculus and arista (one subtype of trichoid sensilla, one subtype of basiconic sensilla, and four subtypes of coeloconic sensilla). Sensilla on the antennal funiculus from one sample of both male and female flies were also mapped. Female P. magnifica bear a larger number of sensilla than males, and more sensilla were discovered on the posterior surface than on the anterior surface. However, what make this species special are the distinct structures and new morphological characteristics discovered in the antenna. The antennal funiculus of P. magnifica is completely enveloped by an antennal pedicel. A large number of branched or unbranched trichoid and basiconic sensilla are identified on the antennal funiculus. These two make the most numerous types of sensilla distributed all over the funicular surface. P. magnifica has the most coeloconic sensilla subtypes in previously studied oestrid flies. A total of four subtypes of coeloconic sensilla are found, with subtype I and subtype II on the proximal and middle part of the antennal funiculus and subtype III and subtype IV on the antennal arista. Two large bristles that resemble mechanoreceptors on the proximal two antennal segments located close to the arista are a unique feature. This has never been described in the oestrid funiculus. Interestingly, these bristles can appear as multi tipped short structures in some individuals. P. magnifica lacks sensory pits that are usually abundant in other oestrid flies. The size, number, and distribution of sensilla on the male and female antennal funiculus are provided here, armed with a discussion of their presumable sensilla functions and evolutionary trends. PMID- 22777703 TI - Use of a simple DNA extraction method for high-throughput detection of filarial parasite Wuchereria bancrofti in the vector mosquitoes. AB - Molecular xenomonitoring of filariasis is the detection of filarial DNA in mosquitoes by PCR and a useful tool for monitoring transmission. DNA extraction coupled with PCR allows rapid detection of the presence or absence of the filarial parasite in vector mosquitoes compared to traditional method of manual dissection of the mosquito and observation for parasite under a microscope. A Tris-EDTA (TE) buffer-based boiling method of DNA extraction developed earlier by us was employed and explored for its suitability in the detection of Wuchereria bancrofti DNA in pools of Culex quinquefasciatus mosquitoes in real-time PCR assay. In this preliminary study, 1,000 laboratory-reared C. quinquefasciatus were made into 40 pools, each containing 25 mosquitoes spiked with 2mf. DNA from the first 20 pools was extracted using Qiagen DNeasy blood and tissue kit as standard, and the other 20 pools were subjected to TE buffer-based boiling method of DNA extraction. When the results (Ct values) obtained for DNA samples extracted by TE buffer-based boiling method were compared with that of the DNA samples extracted by the standard Qiagen method, they were found to be highly concordant without any significant difference (P = 0.9). Besides being cost- and time-effective, this protocol was found useful in extracting filarial DNA from two other mosquito genus Aedes and Anopheles, species of which have been reported as important vectors of W. bancrofti in other endemic regions of the world. Thus, TE buffer-based boiling method of DNA extraction is useful for the high throughput detection of W. bancrofti in vector mosquitoes. PMID- 22777704 TI - Bioefficacy of essential oils of medicinal plants against housefly, Musca domestica L. AB - The housefly Musca domestica L. is recognized as a public health pest causing a serious threat to human and livestock by vectoring many infectious diseases. Chemical control method commonly used against this pest, though effective, has some major disadvantages, such as development of insect resistance and bioaccumulation. Pest management strategies for populations of houseflies are needed. Presently, bioinsecticides, especially those derived from plant origin, have been increasingly evaluated in controlling insects of medical importance. In order to search for effective and ecofriendly control agents, the essential oils of Mentha piperita, Zingiber officinalis, Emblica officinalis, and Cinnamomum verum were evaluated for their larvicidal, attractant/repellent, and oviposition attractant/deterrent activity against M. domestica. The highest larvicidal activity, i.e., C(50) = 104 ppm was shown by M. piperita. This oil also exhibited 96.8% repellency at the concentration of 1%. The highest oviposition deterrence activity of 98.1% was also exhibited by M. piperita oil at the concentration of 1%. Among the remaining plants, the essential oil of Z. officinalis exhibited significant bioactivities against M. domestica with larvicidal activity, i.e., lethal concentration (LC)(50) = 137 ppm, repellency of 84.9 and 98.1% oviposition deterrence both at 1% concentration. The other two plant oils, viz., C. verum and E. officinalis, showed relatively moderate bioefficacy with larvicidal activity, i.e., LC(50) = 159 and 259 ppm, repellency of 77.9 and 63.0% while oviposition deterrence of 60.0 and 42.6%, respectively. The result revealed that the essential oils of M. piperita have control potential against M. domestica and should be further explored as a component of integrated vector management program. PMID- 22777705 TI - Both IFN-gamma and IL-17 are required for the development of severe autoimmune gastritis. AB - IL-17, produced by a distinct lineage of CD4(+) helper T (Th) cells termed Th17 cells, induces the production of pro-inflammatory cytokines from resident cells and it has been demonstrated that over-expression of IL-17 plays a crucial role in the onset of several auto-immune diseases. Here we examined the role of IL-17 in the pathogenesis of autoimmune gastritis, a disease that was previously believed to be mediated by IFN-gamma. Significantly higher levels of IL-17 and IFN-gamma were found in the stomachs and stomach-draining lymph nodes of mice with severe autoimmune gastritis. Unlike IL-17, which was produced solely by CD4(+) T cells in gastritic mice, the majority of IFN-gamma-producing cells were CD8(+) T cells. However, CD8(+) T cells alone were not able to induce autoimmune gastritis. T cells that were deficient in IL-17 or IFN-gamma production were able to induce autoimmune gastritis but to a much lower extent compared with the disease induced by wild-type T cells. These data demonstrate that production of neither IL-17 nor IFN-gamma by effector T cells is essential for the initiation of autoimmune gastritis, but suggest that both are required for the disease to progress to the late pathogenic stage that includes significant tissue disruption. PMID- 22777706 TI - Fructose dehydration to 5-hydroxymethylfurfural over solid acid catalysts in a biphasic system. AB - Different acidic heterogeneous catalysts like alumina, aluminosilicate, zirconium phosphate, niobic acid, ion-exchange resin Amberlyst-15, and zeolite MOR have been studied in fructose dehydration to 5-hydroxymethylfurfural (HMF). The acidity of these materials was characterized using temperature-programmed desorption of NH3 and IR spectroscopy of adsorbed pyridine. The nature and strength of acid sites was shown to play a crucial role in the selectivity towards HMF. Bronsted acid sites in the case of zeolites and ion-exchange resin led to high selectivities in the dehydration of fructose with an increase in selectivity with the addition of an organic phase. Lewis acidity in the case of phosphate and oxides resulted in the intensive production of humins from fructose at the initial stages of the process, whereas organic phase addition did not affect selectivity. PMID- 22777707 TI - Small molecule-gold nanorod conjugates selectively target and induce macrophage cytotoxicity towards breast cancer cells. AB - Gold nanoparticles are known to activate anti-tumor potential in macrophage immune cells; however, the subsequent effects of these cells on others nearby are poorly understood. A novel gold-nanoparticle conjugate that selectively targets and induces cytotoxic activity of tumor-associated macrophages towards breast cancer cells in co-culture is synthesized. These constructs are promising new tools for studying fundamental biological interactions with nanoscale materials and candidates for emerging macrophage-mediated delivery applications. PMID- 22777708 TI - The quest for new mild and selective modifications of natural structures: laccase catalysed oxidation of ergot alkaloids leads to unexpected stereoselective C-4 hydroxylation. AB - Laccase-catalysed oxidation of ergot alkaloids in the absence of chemical mediators allowed the unexpected isolation of the mono-hydroxylated derivatives of compounds 2-7. Structure determination by NMR techniques clearly indicated that hydroxylation took place at the C-4 benzylic position. Quite notably, the proposed protocol allowed, for the first time, functionalisation at the C-4 position of the ergoline skeleton. Depending on the absence or on the presence of a C-10 alpha-methoxy substituent, hydroxylation was either stereoselective (furnishing C-4alpha OH derivatives) or gave rise to a C-4alpha/C-4beta OH mixture in a 2:1 ratio, respectively. PMID- 22777710 TI - Selective rhodium(III)-catalyzed cross-dehydrogenative coupling of furan and thiophene derivatives. PMID- 22777711 TI - Impact of latently infected cells on strain archiving within HIV hosts. AB - Latently infected cells are a barrier to HIV eradication on therapy due to long half-lives of between 6 and 44 months. The mechanism behind this long term maintenance is unclear although bystander proliferation and asymmetric division have both been put forward for consideration in mathematical models. The latently infected cell reservoir seems to act as an archive for strains of HIV no longer dominant in the blood, such as wild-type virus when the individual is on therapy. This is particularly significant when patients wish to come off medication and wild-type virus re-emerges. We use a two target cell model capable of producing low-level viral load on therapy and include latent cells and two strains of virus, wild-type and drug resistant, to investigate the impact of two possible mechanisms of latent cell reservoir maintenance on strain archiving. We find that although short term (less than a year) archiving of viral strains is possible in a model with no mechanism for reservoir maintenance, both bystander proliferation and asymmetric division of latent cells allow archiving to occur over much longer timescales (2 or more years). We suggest that regardless of the mechanism involved, latent cell reservoir maintenance allows strain archiving to occur. We interpret our results for clinical consideration. PMID- 22777709 TI - Frontiers in pulmonary hypertension in infants and children with bronchopulmonary dysplasia. AB - Pulmonary hypertension (PH) is an increasingly recognized complication of premature birth and bronchopulmonary dysplasia (BPD), and is associated with increased morbidity and mortality. Extreme phenotypic variability exists among preterm infants of similar gestational ages, making it difficult to predict which infants are at increased risk for developing PH. Intrauterine growth retardation or drug exposures, postnatal therapy with prolonged positive pressure ventilation, cardiovascular shunts, poor postnatal lung and somatic growth, and genetic or epigenetic factors may all contribute to the development of PH in preterm infants with BPD. In addition to the variability of severity of PH, there is also qualitative variability seen in PH, such as the variable responses to vasoactive medications. To reduce the morbidity and mortality associated with PH, a multi-pronged approach is needed. First, improved screening for and increased recognition of PH may allow for earlier treatment and better clinical outcomes. Second, identification of both prenatal and postnatal risk factors for the development of PH may allow targeting of therapy and resources for those at highest risk. Third, understanding the pathophysiology of the preterm pulmonary vascular bed may help improve outcomes through recognizing pathways that are dysregulated in PH, identifying novel biomarkers, and testing novel treatments. Finally, the recognition of conditions and exposures that may exacerbate or lead to recurrent PH is needed to help with developing treatment guidelines and preventative strategies that can be used to reduce the burden of disease. PMID- 22777712 TI - A method of computing accurate 3D fields of a quadrupole mass filter and their use for prediction of filter behavior. AB - A method is described that enables the three-dimensional fields of a simple quadrupole mass filter (QMF) to be determined to a high accuracy. The technique produces accurate field values in the fringe field region as well as in the center of the filter. Using fields obtained typical filter performance is determined and shown to differ from that predicted when fringe fields are ignored. The computed performance shows features obtained experimentally and displays more complex variation with ion mass and other parameters than when fringe fields are ignored. PMID- 22777713 TI - In honor of Professor Lester A. Mitscher on the occasion of his 80(th) birthday. PMID- 22777715 TI - Sex-related differences in prognosis after myocardial infarction: changes from 1978 to 2007. AB - Women with myocardial infarction (MI) have shown a 28-day survival disadvantage compared with men. However, results were less consistent when considering long term mortality in 28-day survivors. The aim was to estimate the trends for sex related differences in the three endpoints considered for this study: (1) 28-day mortality or severe ventricular dysfunction (acute pulmonary oedema or cardiogenic shock) during the hospital stay, (2) 28-day mortality and (3) two year cardiovascular mortality or non-fatal MI in 28-day survivors after a first MI. A cohort of 3,982 consecutive patients with first Q-wave MI admitted to a university tertiary reference hospital between 1978 and 2007 was followed for 2 years. Short-term prognosis improved in women over the studied period; similar rates were observed in both sexes in the 2000s. After adjusting for age, co morbidities and anterior location of MI, female sex had an odds ratio=1.71 (95% confidence interval [CI] 1.34-2.17) of short-term severe MI or death over the studied period. Overall, sex differences in long-term prognosis remained similar over the studied period (hazard ratio=1.40; 95% CI 1.02-1.91). In conclusion, short-term prognosis improved over the past 30 years for first Q-wave MI patients, becoming similar for both men and women in the most recent decade. Long term prognosis did not improve in either men or women, indicating that secondary prevention should be reinforced to achieve consistent reductions in the number of cardiovascular events. PMID- 22777716 TI - Intelligence level in late adolescence is inversely associated with BMI change during 22 years of follow-up: results from the WICTORY study. AB - The objective of this population-based retrospective cohort study was to examine the association between intelligence (IQ) at late adolescence and changes in body mass index (BMI) during 22 years of follow-up until 40 years of age, taking education level into account. Data from 5,286 males born 1950-1959 who had participated in the Westmannia Cardiovascular Risk Factors Study at 40 years of age and attended the Swedish military conscription examination between the ages of 17 and 22 were used. From a mean age of 18 years until follow-up at 40 years of age, BMI increased with a mean (95 % confidence interval (CI)) of 4.36 (4.28 4.43) kg/m(2), equalling 0.20 kg/m(2) per year. The difference in BMI change between IQ levels was strongly statistically significant (P < 0.001), with a strictly inverse relationship between IQ and BMI change. The lowest IQ level (<74) had a mean (95 % CI) BMI increase of 5.19 (4.63-5.74) kg/m(2), equalling 0.24 kg/m(2) per year, compared with 3.73 (3.40-4.07) kg/m(2), equalling 0.17 kg/m(2) per year, for the highest IQ level (>126). Education level also had a strictly inverse relationship with BMI change. After adjusting for confounding variables, including education level, IQ still had a strictly inverse relationship to BMI change, with all IQ levels < 111 having a significantly larger BMI change than IQ > 126 (P < 0.01 for all levels). Education level at 40 years of age but not at 18 years of age had a significant association with BMI change after adjusting for IQ. PMID- 22777718 TI - Design and synthesis of tryptophan containing peptides as potential analgesic and anti-inflammatory agents. AB - A new series of smaller peptides with tryptophan at C-terminal and varying N protected amino acids/peptides were designed, synthesized and characterized by analytical and spectroscopic techniques. Analgesic and anti-inflammatory properties of these peptides were carried out in vivo using tail-flick method and carrageenan-induced paw edema method, respectively, at different doses and different time intervals. Most of the peptides synthesized displayed enhanced activity, and particularly tetra and hexapeptides 29-31 were found to be even more potent than the reference standards used. Moreover, some peptides have exhibited promising activity even after 24 h of administration, whereas the reference standards were active only up to 3 h. Further, the compounds did not present any ulcerogenic liability. PMID- 22777717 TI - Clinicopathological significance of NUT rearrangements in poorly differentiated malignant tumors of the upper respiratory tract. AB - Nuclear protein in testis (NUT) midline carcinoma (NMC) is a highly malignant carcinoma originating from the midline of the body. This study investigated the clinicopathological significance of NUT rearrangements in poorly differentiated malignant tumors (PDMTs) of the upper-respiratory tract (URT) in China. The clinical and pathological features of 155 PDMTs of the URT were reviewed. Epstein Barr virus (EBV)-encoded RNA and NUT were investigated by in situ hybridization and immunohistochemistry (IHC), respectively. NUT-positive cases were examined by fluorescence in situ hybridization (FISH) and immunohistochemical staining with a set of cytokeratins (CKs) and neuroendocrine markers. One case was observed by transmission electron microscopy. Four cases of poorly differentiated squamous cell carcinomas and sinonasal undifferentiated carcinomas were diffuse positive for NUT by IHC and also stained for antibodies to CKs and P63 but were negative for neuroendocrine markers. Only 2 of these 4 cases showed rearrangements of the NUT and BRD4 genes by FISH; both these patients died within 12 months. The remaining 2 patients showed no NUT rearrangement by FISH and did not have an aggressive clinical course. NMC is a rare, poorly differentiated carcinoma, which occurs most often in midline organs, and in this first series from China, affected the sinonasal tract of older adults and was not associated with EBV infection. Determination of NUT protein expression and gene rearrangement can allow the differentiation of NMC from other URT PDMTs. The authors suggest that molecular determination of NUT gene rearrangements should therefore represent the gold standard for NMC diagnosis. PMID- 22777719 TI - Statistical methods for test and biomarker evaluation studies: a clinical chemistry series. PMID- 22777720 TI - Comprehensive one-step molecular analyses of mitochondrial genome by massively parallel sequencing. AB - BACKGROUND: Mitochondrial diseases are clinically and genetically heterogeneous, with variable penetrance, expressivity, and differing age of onset. Disease causing point mutations and large deletions in the mitochondrial genome often exist in a heteroplasmic state. Current molecular analyses require multiple different and complementary methods for the detection and quantification of mitochondrial DNA (mtDNA) mutations. We developed a novel approach to analyze the mtDNA in 1 step. METHODS: The entire human mitochondrial genome was enriched by a single amplicon long-range PCR followed by massively parallel sequencing to simultaneously detect mtDNA point mutations and large deletions with heteroplasmic levels of the mutations and variants quantified. QC samples were designed and analyzed along with each sample. A total of 45 samples were analyzed for the evaluation of analytic sensitivity and specificity. RESULTS: Our analysis demonstrated 100% diagnostic sensitivity and specificity of base calls compared to the results from Sanger sequencing. The deep coverage allowed the detection and quantification of heteroplasmy at every single nucleotide position of the 16 569-bp mitochondrial genome. Moreover, the method also detected large deletions with the breakpoints mapped. CONCLUSIONS: This "deep" sequencing approach provides a 1-step comprehensive molecular analysis of the whole mitochondrial genome for patients in whom a mitochondrial disease is suspected. PMID- 22777714 TI - Chemical and biochemical approaches in the study of histone methylation and demethylation. AB - Histone methylation represents one of the most critical epigenetic events in DNA function regulation in eukaryotic organisms. Classic molecular biology and genetics tools provide significant knowledge about mechanisms and physiological roles of histone methyltransferases and demethylases in various cellular processes. In addition to this stream line, development and application of chemistry and chemistry-related techniques are increasingly involved in biological study, and offer information otherwise difficult to obtain by standard molecular biology methods. Herein, we review recent achievements and progress in developing and applying chemical and biochemical approaches in the study of histone methylation, including chromatin immunoprecipitation, chemical ligation, mass spectrometry, biochemical methylation and demethylation assays, and inhibitor development. These technological advances allow histone methylation to be studied from genome-wide level to molecular and atomic levels. With ChIP technology, information can be obtained about precise mapping of histone methylation patterns at specific promoters, genes, or other genomic regions. MS is particularly useful in detecting and analyzing methylation marks in histone and nonhistone protein substrates. Chemical approaches that permit site-specific incorporation of methyl groups into histone proteins greatly facilitate the investigation of biological impacts of methylation at individual modification sites. Discovery and design of selective organic inhibitors of histone methyltransferases and demethylases provide chemical probes to interrogate methylation-mediated cellular pathways. Overall, these chemistry-related technological advances have greatly improved our understanding of the biological functions of histone methylation in normal physiology and diseased states, and also are of great potential to translate basic epigenetics research into diagnostic and therapeutic applications in the clinic. PMID- 22777721 TI - Transhepatic approach to create stent fenestration in the extracardiac Fontan conduit in a child with dextrocardia and interrupted inferior vena cava with azygos continuation. AB - Plastic bronchitis is a rare life-threatening complication of Fontan operation. When medical treatment is ineffective in the setting of high systemic venous pressures, Fontan fenestration may be considered to decompress venous pressures and improve cardiac output by creation of the right-to-left shunting. However, transcatheter approach can be difficult in patients with complex venous anatomy. We report a 4-year-old girl born with hypoplastic left ventricle and heterotaxy syndrome, who developed plastic bronchitis following extracardiac Fontan procedure. Her venous anatomy was complex with dextrocardia and interrupted inferior vena cava with azygos continuation. Stent fenestration was successfully performed via transhepatic approach, which was selected based on the anatomical relationship (between extracardiac conduit, left atrium, and hepatic veins) delineated by pre-catheterization cardiac MRI. Simultaneous transesophageal echocardiography guided the intervention. Her plastic bronchitis improved significantly in 3 months but slowly progressed after the stent fenestration. At her 8-month follow-up, stent fenestration remains open and she is currently under heart transplantation evaluation due to persistent plastic bronchitis. Treatment of plastic bronchitis can be undertaken with Fontan fenestration, with pre procedural MRI playing an essential role in patients with complex venous anatomy. PMID- 22777722 TI - Obesity and incidence of lung cancer: a meta-analysis. AB - To date, the relationship between obesity and the incidence of lung cancer remains unclear and inconclusive. Thus, we conducted a meta-analysis of published studies to provide a quantitative evaluation of this association. Relevant studies were identified through PubMed and EMBASE databases from 1966 to December 2011, as well as through the reference lists of retrieved articles. A total of 31 articles were included in this meta-analysis. Overall, excess body weight (body mass index, BMI >= 25 kg/m(2)) was inversely associated with lung cancer incidence (relative risk, RR = 0.79; 95% confidence interval, CI: 0.73-0.85) compared with normal weight (BMI = 18.5-24.9 kg/m(2)). The association did not change with stratification by sex, study population, study design, and BMI measurement method. However, when stratified by smoking status, the inverse association between excess body weight and lung cancer incidence in current (RR = 0.63, 95% CI: 0.57-0.70) and former (RR = 0.73, 95% CI: 0.58-0.91) smokers was strengthened. In non-smokers, the association was also statistically significant (RR = 0.83, 95% CI: 0.70-0.98), although the link was weakened to some extent. The stratified analyses also showed that excess body weight was inversely associated with squamous cell carcinoma (RR = 0.68, 95% CI: 0.58-0.80) and adenocarcinoma (RR = 0.79, 95% CI: 0.65-0.96). No statistically significant link was found between excess body weight and small cell carcinoma (RR = 0.99, 95% CI: 0.66-1.48). The results of this meta-analysis indicate that overweight and obesity are protective factors against lung cancer, especially in current and former smokers. PMID- 22777723 TI - A rapid approach to the preliminary assessment of the physical stability of pharmaceutical hydrates. AB - Pharmaceutical hydrates have been used as clinical development candidates and in marketed products. The physical stability of hydrates can pose unique challenges to their development because of their particular sensitivity to the moisture levels in their surroundings. By conducting simple experiments early during the form selection phase of a drug candidate's development, a basic understanding of the thermodynamic and kinetic aspects of a hydrate form's stability can be attained that can facilitate the successful navigation of these challenges. Differential scanning calorimetry was used to determine the thermal and kinetic properties of a number of pharmaceutically relevant hydrates. The activation energy (E(a)) of dehydration and dehydration onset temperature (T(onset)) of survey compounds were compiled and analyzed. A significant number of compounds possessed both high E(a) and high T(onset) of dehydration, suggesting that these hydrate crystal forms were particularly stable. The results of these studies suggest that dehydration E(a) and dehydration T(onset) together can be used as early indicators of a crystalline hydrate's physical stability and can alert to potential challenges in developing hydrate crystal forms of drug candidates. PMID- 22777724 TI - Antiinflammatory strategies, not just B cell depletion, are required for optimal therapy for severe proliferative lupus nephritis: comment on the article by Rovin et al. PMID- 22777725 TI - Orchestrating cell/material interactions for tissue engineering of surgical implants. AB - Research groups are currently recognising a critical clinical need for innovative approaches to organ failure and agenesis. Allografting, autologous reconstruction and prosthetics are hampered with severe limitations. Pertinently, readily available 'laboratory-grown' organs and implants are becoming a reality. Tissue engineering constructs vary in their design complexity depending on the specific structural and functional demands. Expeditious methods on integrating autologous stem cells onto nanoarchitectured 3D nanocomposites, are being transferred from lab to patients with a number of successful first-in-man experiences. Despite the need for a complete understanding of cell/material interactions tissue engineering is offering a plethora of exciting possibilities in regenerative medicine. PMID- 22777726 TI - Methicillin-resistant Staphylococcus aureus sinusitis in nonhospitalized patients: a systematic review of prevalence and treatment outcomes. AB - OBJECTIVES/HYPOTHESIS: Methicillin-resistant Staphylococcus aureus (MRSA) has been isolated from patients with acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS), although the exact prevalence is unknown. Similarly, the optimal treatment regimen for MRSA sinusitis has not been determined. The aim of this study was to summarize the existing data on prevalence and treatment outcomes for MRSA sinusitis in nonhospitalized patients. STUDY DESIGN: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: MEDLINE, Embase, and Cochrane databases were queried for English-language studies published between 1942 and 2012. Studies were excluded that did not provide quantitative data on the prevalence or treatment of ARS or CRS with MRSA-positive cultures. An itemized assessment of the risk of bias was conducted for each included study. RESULTS: Of 409 studies identified during systematic review, 12 studies met the criteria for analysis. The level of evidence and freedom from bias of these studies were generally low. The prevalence of MRSA among all culture isolates ranged from 0% to 15.9% for ARS and 1.8% to 20.7% for CRS. Six studies reported quantitative treatment outcomes using variable measures, in which resolution of infection ranged from 58.3% to 100%. The treatment regimens were heterogeneous and included single- and multiple-agent therapy with oral, topical, and parental antibiotics. CONCLUSIONS: MRSA-positive cultures are found in a small but significant number of cases of ARS and CRS. Treatment of MRSA sinusitis may be effective, although treatment regimens and outcome measures are variable. Prospective studies utilizing standardized parameters are warranted. PMID- 22777727 TI - The economic burden of atherothrombosis in Greece: results from the THESIS study. AB - The aim of this study was to estimate the total annual cost of patients with or at risk for atherothrombosis in Greece. A multicentre, cost-of-illness study was conducted between January 2007 and December 2009. In the study, 800 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease (PAD) or multiple cardiovascular risk factors (MRF) were recruited. Direct and indirect cost data were assessed at patients' enrolment in the study, and at 6 and 12 months of follow-up. The annual total cost was ?6,017/patient. This cost ranged from ?10,098/patient with PAD to ?1,813/patient with MRF. The annual direct health-care cost was ?5,056/patient. This cost escalates from ?1,623/patient with MRF to ?8,697/patient with PAD. The total annual expenditures related to atherothrombosis, in Greece, were estimated to be ?7.5 billion at the national level. The findings of the current study indicate the high economic burden of atherothrombosis in Greece. PMID- 22777728 TI - Integration of biological networks and pathways with genetic association studies. AB - Millions of genetic variants have been assessed for their effects on the trait of interest in genome-wide association studies (GWAS). The complex traits are affected by a set of inter-related genes. However, the typical GWAS only examine the association of a single genetic variant at a time. The individual effects of a complex trait are usually small, and the simple sum of these individual effects may not reflect the holistic effect of the genetic system. High-throughput methods enable genomic studies to produce a large amount of data to expand the knowledge base of the biological systems. Biological networks and pathways are built to represent the functional or physical connectivity among genes. Integrated with GWAS data, the network- and pathway-based methods complement the approach of single genetic variant analysis, and may improve the power to identify trait-associated genes. Taking advantage of the biological knowledge, these approaches are valuable to interpret the functional role of the genetic variants, and to further understand the molecular mechanism influencing the traits. The network- and pathway-based methods have demonstrated their utilities, and will be increasingly important to address a number of challenges facing the mainstream GWAS. PMID- 22777730 TI - Female effects on offspring energetic status and consequences on early development in yolk feeding brown trout (Salmo trutta). AB - Energetic status can be defined as the interaction between energy stores and metabolic rate. In salmonids, it is variable and influences the timing of emergence, and therefore may have strong effects on both juvenile and maternal fitness. The aim of this study is to (i) describe the ontogeny of energy use for different brown trout clutches to understand how such a variability of energetic status is developed at the end of incubation and (ii) to estimate maternal influences over offspring physiological processes. Using individual measures of total mass and metabolism throughout ontogeny combined with a hierarchical Bayesian modeling approach, we successfully described clutch-specific (i) metabolic trajectories, (ii) use of yolk resources and the building of new tissues throughout ontogeny. Our results show that females laying large eggs have offspring with lower metabolic costs and higher yolk conversion efficiencies. Females also influence within clutch variance of metabolic and yolk consumption rates leading to potential developmental variations. These results are discussed with regard to their consequences on early life history through the critical period of emergence. PMID- 22777729 TI - In vitro and in vivo studies of 17O NMR sensitivity at 9.4 and 16.4 T. AB - In vivo 17O magnetic resonance spectroscopy has been successfully applied for imaging the cerebral metabolic rate of oxygen consumption through the detection of metabolically produced H2(17)O from the inhaled 17O-labeled oxygen in animals at high field. In this study, we compared the 17O sensitivity for detecting natural abundance H2(17)O signals from a phantom solution and rat brains at 9.4 and 16.4 T. The 17O signal-to-noise ratio measured at 16.4 T was 2.9- and 2.7-2.8 fold higher than that at 9.4 T for the phantom and rat brain studies, respectively. Similarly, three-dimensional 17O magnetic resonance spectroscopy imaging data showed a more than 2.7-fold higher signal-to-noise ratio in the central rat brain region at 16.4 T than that at 9.4 T. The substantial 17O signal to-noise ratio gain at ultrahigh field significantly improved the reliability for imaging the cerebral metabolic rate of oxygen consumption and will provide an opportunity for in vivo assessment of altered oxidative metabolism associated with brain functions and neurological diseases. PMID- 22777731 TI - Water vapor permeability of the rigid-shelled gecko egg. AB - The vast majority of squamate reptiles (lizards and snakes) produce parchment shelled eggs that absorb water during incubation, and thus increase in mass, volume, and surface area. In contrast, females from a single monophyletic lineage of gekkotan lizards produce rigid-shelled eggs. These eggs are functionally comparable to those of birds, that is, at oviposition, eggs contain all the water needed for development, and their mass decreases during incubation via the diffusion of water vapor through the shell. I determined patterns of water loss and shell permeability to water vapor from oviposition to hatching for the rigid shelled eggs of the gekkonid Chrondrodactylus turneri and compared permeability of C. turneri eggs to those of birds and other squamates. Chrondrodactylus turneri eggs incubated at 28.5 degrees C and 40% relative humidity (RH) decreased in mass by 14% over the course of a 68-day incubation period. The rate of water loss varied during incubation; egg mass decreased rapidly during the first 8 days of incubation, declined at a low constant rate during the next 35 days, and then decreased rapidly during the final 25 days of incubation. Overall permeability was 0.17 mg/day/kPa/cm(2) . Percent water loss of rigid-shelled gecko eggs during incubation is similar to that exhibited by birds, but water vapor permeability is about one-third that of bird eggs and several orders of magnitude lower than that of parchment-shelled squamate eggs. In general, the water economy of their eggs may be associated with the adaptive radiation of the rigid-shelled sphaerodactylid, phyllodactylid, and gekkonid geckos. PMID- 22777732 TI - Chromosomal aberrations, Yq microdeletion, and sperm DNA fragmentation in infertile men opting for assisted reproduction. AB - Male infertility is a multi-factorial disorder, and identification of its etiology in an individual is critical for treatment. Systematically elucidating the underlying genetic causes (chromosomal and Yq microdeletion) and factors, such as reactive oxygen species (ROS) levels and total antioxidant capacity (TAC), which contribute to sperm DNA damage, may help to reduce the number of men with idiopathic infertility and provide them with the most suitable therapeutics and counseling. This study was done to comprehensively investigate genetic and oxidative stress factors that might be the etiology of a large percentage of men with idiopathic infertility. One hundred twelve infertile men and 76 fertile controls were screened for chromosomal aberrations and Yq microdeletions. ROS, TAC, and sperm DNA damage were assessed in cytogenetically normal, non azoospermic men with intact Y chromosome (n = 93). ROS was assessed in neat and washed semen by chemiluminescence; seminal TAC with a commercially available kit; and sperm DNA damage by the comet assay. Two men had cytogenetic abnormalities and seven men harbored Yq microdeletions. ROS levels in neat and washed semen of infertile men were significantly higher (P < 0.01) than controls. Infertile men had significantly lower (P < 0.01) TAC levels (1.79 mM), whereas sperm DNA fragmentation in infertile men was significantly higher (P < 0.01) than controls. Genetic factors and oxidative stress cumulatively account for large number of idiopathic infertile cases. Unlike, genetic causes, which cannot be cured, timely identification and management of oxidative stress may help to reverse/reduce the effects on induced DNA damage, and improve the outcomes for infertile males. PMID- 22777733 TI - Frequency of the first feature in action sequences influences feature binding. AB - We investigated whether binding among perception and action feature codes is a preliminary step toward creating a more durable memory trace of an action event. If so, increasing the frequency of a particular event (e.g., a stimulus requiring a movement with the left or right hand in an up or down direction) should increase the strength and speed of feature binding for this event. The results from two experiments, using a partial-repetition paradigm, confirmed that feature binding increased in strength and/or occurred earlier for a high-frequency (e.g., left hand moving up) than for a low-frequency (e.g., right hand moving down) event. Moreover, increasing the frequency of the first-specified feature in the action sequence alone (e.g., "left" hand) increased the strength and/or speed of action feature binding (e.g., between the "left" hand and movement in an "up" or "down" direction). The latter finding suggests an update to the theory of event coding, as not all features in the action sequence equally determine binding strength. We conclude that action planning involves serial binding of features in the order of action feature execution (i.e., associations among features are not bidirectional but are directional), which can lead to a more durable memory trace. This is consistent with physiological evidence suggesting that serial order is preserved in an action plan executed from memory and that the first feature in the action sequence may be critical in preserving this serial order. PMID- 22777734 TI - The closer the better: Hand proximity dynamically affects letter recognition accuracy. AB - A growing literature has suggested that processing of visual information presented near the hands is facilitated. In this study, we investigated whether the near-hands superiority effect also occurs with the hands moving. In two experiments, participants performed a cyclical bimanual movement task requiring concurrent visual identification of briefly presented letters. For both the static and dynamic hand conditions, the results showed improved letter recognition performance with the hands closer to the stimuli. The finding that the encoding advantage for near-hand stimuli also occurred with the hands moving suggests that the effect is regulated in real time, in accordance with the concept of a bimodal neural system that dynamically updates hand position in external space. PMID- 22777735 TI - Numerical distance effects in visual search. AB - We present three experiments in which observers searched for a target digit among distractor digits in displays in which the mean numerical target-distractor distance was varied. Search speed and accuracy increased with numerical distance in both target-present and target-absent trials (Exp. 1A). In Experiment 1B, the target 5 was replaced with the letter S. The results suggest that the findings of Experiment 1A do not simply reflect the fact that digits that were numerically closer to the target coincidentally also shared more physical features with it. In Experiment 2, the numerical distance effect increased with set size in both target-present and target-absent trials. These findings are consistent with the view that increasing numerical target-distractor distance affords faster nontarget rejection and target identification times. Recent neurobiological findings (e.g., Nieder, 2011) on the neuronal coding of numerosity have reported a width of tuning curves of numerosity-selective neurons that suggests graded, distance-dependent coactivation of the representations of adjacent numbers, which in visual search would make it harder to reject numerically closer distractors as nontargets. PMID- 22777736 TI - Cooperative assistance in bifunctional organocatalysis: enantioselective Mannich reactions with aliphatic and aromatic imines. AB - Hold them tight: Guided by X-ray structures, bifunctional thiourea catalysts containing an activating intramolecular hydrogen bond were redesigned. The new catalysts were used to effect a highly enantioselective Mannich reaction between malonates and both aliphatic and aromatic imines (see scheme; Boc=tert butoxycarbonyl). PMID- 22777737 TI - Autoimmunity-mediated antitumor immunity: tumor as an immunoprivileged self. AB - The association of autoimmunity with antitumor immunity challenges a paradigm of selective surveillance against tumors. Aided with well-characterized models of robust autoimmunity, we show that self-antigen-specific effector T (Teff) cell clones could eradicate tumor cells. However, a tumor microenvironment reinforced by Treg cells and myeloid-derived suppressor cells (MDSCs) presented a barrier to the autoimmune effectors, more so in tumors than in healthy tissues. This barrier required optimal CTLA4 expression in Teff cells. In a spontaneous model of breast cancer, subtle reductions in CTLA4 expression impeded tumor onset and progression, providing the first direct evidence that CTLA4 inhibits spontaneous tumor development. In an adoptive therapy model of lymphoma, self-antigen specific Teff cells were potentiated by even a modest reduction of CTLA4. A subtle reduction of CTLA4 did not curtail Treg-cell suppression. Thus, Teff cells had an exquisite sensitivity to physiological levels of CTLA4 variations. However, both Treg and Teff cells were impacted by anti-CTLA4 antibody blockade. Therefore, whether CTLA4 impacts through Treg cells or Teff cells depends on its expression level. Overall, the results suggest that the tumor microenvironment represents an "immunoprivileged self" that could be overcome practically and at least partially by RNAi silencing of CTLA4 in Teff cells. PMID- 22777739 TI - Facile aqueous-phase synthesis of biocompatible and fluorescent Ag2S nanoclusters for bioimaging: tunable photoluminescence from red to near infrared. AB - Low toxicity and fluorescent nanomaterials have many advantages in biological imaging. Herein, a novel and facile aqueous-phase approach to prepare biocompatible and fluorescent Ag(2)S nanoclusters (NCs) is designed and investigated. The resultant Ag(2)S NCs show tunable luminescence from the visible red (624 nm) to the near infrared (NIR; 724 nm) corresponding to the increasing size of the NCs. The key for preparing tunable fluorescent Ag(2)S NCs is the proper choice of capping reagent, glutathione (GSH), and the novel sulfur hydrazine hydrate complex as the S(2-) source. As a naturally occurring and readily available tripeptide, GSH functions as an important scaffold to prevent NCs from growing large nanoparticles. Additionally, GSH is a small biomolecule with several functional groups, including carboxyl and amino groups, which suggests the resultant Ag(2)S NCs are well-dispersed in aqueous solution. These advantages make the as-prepared Ag(2)S NCs potentially applicable to biological labeling as well. For example, the resultant Ag(2)S NCs are used as a probe for MC3T3-EI cellular imaging. PMID- 22777738 TI - Neonatal non-invasive respiratory support: physiological implications. AB - The introduction of assisted ventilation for neonatal pulmonary insufficiency has resulted in the successful treatment of many previously fatal diseases. During the past three decades, refinement of invasive mechanical ventilation techniques has dramatically improved survival of many high-risk neonates. However, as with many advances in medicine, while mortality has been reduced, morbidity has increased in the surviving high-risk neonate. In this regard, introduction of assisted ventilation has been associated with chronic lung injury, also known as bronchopulmonary dysplasia. This disease, unknown prior to the appearance of mechanical ventilation, has produced a population of patients characterized by ventilator or oxygen dependence with serious accompanying pulmonary and neurodevelopmental morbidity. The purpose of this article is to review non invasive respiratory support methodologies to address the physiologic mechanisms by which these methods may prevent the pathophysiologic effects of invasive mechanical ventilation. PMID- 22777740 TI - Fluoro-Sorafenib (Regorafenib) effects on hepatoma cells: growth inhibition, quiescence, and recovery. AB - To evaluate the growth-inhibitory properties of the potent multi-kinase antagonist Regorafenib (Fluoro-Sorafenib), which was synthesized as a more potent Sorafenib, a Raf inhibitor and to determine whether similar mechanisms were involved, human hepatoma cell lines were grown in the presence or absence of Regorafanib and examined for growth inhibition. Western blots were performed for Raf targets, apoptosis, and autophagy. Regorafenib inhibited growth of human Hep3B, PLC/PRF/5, and HepG2 cells in a concentration- and time-dependent manner. Multiple signaling pathways were altered, including MAP kinases phospho-ERK and phospho-JNK and its target phospho-c-Jun. There was evidence for apoptosis by FACS, cleavage of caspases and increased Bax levels; as well as induction of autophagy, as judged by increased Beclin-1 and LC3 (II) levels. Prolonged drug exposure resulted in cell quiescence. Full growth recovery occurred after drug removal, unlike with doxorubicin chemotherapy. Regorafenib is a potent inhibitor of cell growth. Cells surviving Regorafenib treatment remain viable, but quiescent and capable of regrowth following drug removal. The reversibility of tumor cell growth suppression after drug removal may have clinical implications. PMID- 22777741 TI - Tubulin-binding cofactor B is a direct interaction partner of the dynactin subunit p150(Glued). AB - The dynactin p150(Glued) subunit, encoded by the gene DCTN1, is part of the dynein-dynactin motor protein complex responsible for retrograde axonal transport in motor neurons. The p150 subunit is a candidate gene for neurodegenerative diseases, in particular motor neuron and extrapyramidal diseases. Tubulin-binding cofactors are believed to be involved in tubulin biogenesis and degradation and therefore to contribute to microtubule functional diversity and regulation. A yeast-two-hybrid screen for putative interacting proteins of dynactin p150(Glued) has revealed tubulin-folding cofactor B (TBCB). We analyzed the interaction of these proteins and investigated the impact of this complex on the microtubule network in cell lines and primary hippocampal neurons in vitro. We especially concentrated on neuronal morphology and synaptogenesis. Overexpression of both proteins or depletion of TBCB alone does not alter the microtubule network and/or neuronal morphology. The demonstration of the interaction of the transport molecule dynactin and the tubulin-regulating factor TBCB is thought to have an impact on several cellular mechanisms. TBCB expression levels have been found to have only a subtle influence on the microtubule network and neuronal morphology. However, overexpression of TBCB leads to the decreased localization of p150 to the microtubule network that might result in a functional modulation of this protein complex. PMID- 22777742 TI - Cellular bases for interactions between immunocytes and enteroendocrine cells in the intestinal mucosal barrier of rhesus macaques. AB - The roles of the interactions between nervous, endocrine, and immune systems have been well established in human health and diseases. At present, little is known about the cellular bases for neural-endocrine-immune networks in the gastrointestinal mucosa. In the current study, duodenum, jejunum, ileum, cecum, colon, and rectum autopsies from 15 rhesus macaques and endoscopic duodenal biopsies from 12 rhesus macaques were collected, and the spatial relationships between the endocrine cells and immune cells in the intestinal mucosa were examined by transmission electron microscopy. Eight types of enteroendocrine cells similar to human enterochromaffin cells (EC), D1, G, I, K, L, N, and S cells were found to lie within a one-cell-size distance from immunocytes, in particular the eosinophils in the epithelia or lamina propria. Close apposition of large areas of plasma membranes between many types of enteroendocrine cells and immunocytes, especially between EC, K, S cells and eosinophils, were observed in the epithelia for the first time. These data indicate that complex interactions occur between diverse types of enteroendocrine cells and various immune cells through paracrine mechanisms or via mechanisms dependent on cell-to cell contact; such interactions might play key roles in maintaining the gut mucosal barrier integrity of rhesus macaques. PMID- 22777743 TI - Identification and cellular location of glutamine synthetase in human sperm. AB - Glutamine synthetase (GS) catalyzes the de novo synthesis of glutamine, an amino acid that has been shown to influence sperm motility in mammals. To date, no information is available about GS content in human sperm. In this study, we have characterized the presence and cellular location of GS in fresh human normozoospermic samples. We have detected a single band corresponding to GS by Western blot. Confocal analysis has revealed GS immunoreactivity in the post acrosomal head region. Moreover, double-labeling experiments with either F-actin or calicin have demonstrated GS confinement in the post-acrosomal region of the perinuclear theca. These data have been validated by a post-embedding ultra structural study. The presence of GS in the post-acrosomal region of the perinuclear theca suggests that human sperm can carry out in glutamine synthesis. PMID- 22777744 TI - Protein conformational studies for macromolecularly imprinted polymers. AB - CD is used to clearly show the negative impact of common ligands on the overall conformation of BSA, a typical protein template in macromolecularly imprinted polymers. This change occurs at concentrations far lower than those generally used in the literature. These findings are important as they offer insight into a potential fundamental reason for the lack of success in protein imprinting to date despite significant interest from the scientific community. PMID- 22777745 TI - Interactive toxicity of usnic acid and lipopolysaccharides in human liver HepG2 cells. AB - Usnic acid (UA), a natural botanical product, is a constituent of some dietary supplements used for weight loss. It has been associated with clinical hepatotoxicity leading to liver failure in humans. The present study was undertaken to evaluate the interactive toxicity, if any, of UA with lipopolysaccarides (LPS), a potential contaminant of food, at low non-toxic concentrations. The human hepatoblastoma HepG2 cells were treated with the vehicle control and test agents, separately and in a binary mixture, for 24 h at 37 degrees C in 5% CO2. After the treatment period, the cells were evaluated by the traditional biochemical endpoints of toxicity in combination with the toxicogenomic endpoints that included cytotoxicity, oxidative stress, mitochondrial injury and changes in pathway-focused gene expression profiles. Compared with the controls, low non-toxic concentrations of UA and LPS separately showed no effect on the cells as determined by the biochemical endpoints. However, the simultaneous mixed exposure of the cells to their binary mixture resulted in increased cytotoxicity, oxidative stress and mitochondrial injury. The pathway-focused gene expression analysis resulted in the altered expression of several genes out of 84 genes examined. Most altered gene expressions induced by the binary mixture of UA and LPS were different from those induced by the individual constituents. The genes affected by the mixture were not modulated by either UA or LPS. The results of the present study suggest that the interactions of low nontoxic concentrations of UA and LPS produce toxicity in HepG2 cells. PMID- 22777746 TI - Drilling speaking valves to promote phonation in tracheostomy-dependent children. AB - OBJECTIVES/HYPOTHESIS: Placement of a Passy-Muir speaking valve is considered best practice for infants and children with a tracheostomy. The Passy-Muir valve enables phonation by redirecting exhaled air via the glottis. Poor tolerance of the Passy-Muir valve is associated with excessive transtracheal pressures on exhalation due to upper airway obstruction. Drilling a small hole in the side of the Passy-Muir valve creates a pressure relief port to allow partial exhalation through the tracheostomy tube while enabling phonation. STUDY DESIGN: A retrospective case series is presented of 10 aphonic pediatric patients with a tracheostomy trialed with a drilled Passy-Muir valve. METHODS: Valve tolerance was assessed clinically and objectively. Handheld manometry was used to determine transtracheal pressures on passive exhalation. All patients had a diagnosis of upper airway obstruction and demonstrated excessive pressures wearing a standard Passy-Muir valve. Patients were assessed wearing a Passy-Muir valve with up to two 1.6-mm holes drilled in the side of the valve. Patients progressed to trials if clinically stable and if transtracheal pressure did not exceed 10 cm H(2) O when wearing the valve. RESULTS: Eight patients progressed to trial, with five of eight patients able to phonate within 1 week and six of eight able to tolerate wearing the valve for >= 2-hour periods within 2 weeks of introduction. All eight patients were able to phonate within 6 months of valve introduction. CONCLUSIONS: These findings support drilling Passy-Muir speaking valves as a promising option to facilitate phonation in pediatric patients with a tracheostomy for upper airway obstruction. PMID- 22777747 TI - Clinical images: voriconazole-induced periostitis deformans. PMID- 22777748 TI - Macromolecule-suppressed GABA-edited magnetic resonance spectroscopy at 3T. AB - Edited magnetic resonance spectroscopy makes possible noninvasive studies of the role of the inhibitory neurotransmitter GABA in the healthy brain and in disease processes. A major limitation of the methodology is coediting of macromolecular signals. Although it has previously been shown that macromolecular signal can be suppressed using a symmetrical editing scheme, this approach is rarely applied at field strength of 3T as insufficiently selective pulses result in loss of GABA signal (in addition to the intended suppression of macromolecular signal). In this article, the authors show that increasing the echo time to 80 ms lets more selective editing pulses be used, allowing for symmetric editing-based suppression of coedited macromolecular signal without loss of GABA signal. The method is applied to acquire macromolecule-suppressed GABA-edited spectra in 10 healthy participants. PMID- 22777749 TI - Titanium-catalyzed vinylic and allylic C-F bond activation-scope, limitations and mechanistic insight. AB - The hydrodefluorination (HDF) of fluoroalkenes in the presence of a variety of titanium catalysts was studied with respect to scope, selectivity, and mechanism. Optimization revealed that the catalyst requires low steric bulk and high electron density; secondary silanes serve as the preferred hydride source. A broad range of substrates yield partially fluorinated alkenes, such as previously unknown (Z)-1,2-(difluorovinyl)ferrocene. Mechanistic studies indicate a titanium(III) hydride as the active species, which forms a titanium(III) fluoride by H/F exchange with the substrate. The HDF step can follow both an insertion/elimination and a sigma-bond metathesis mechanism; the E/Z selectivity is controlled by the substrate. The catalysts' ineffieciency towards fluoroallenes was rationalized by studying their reactivity towards Group 6 hydride complexes. PMID- 22777750 TI - Can't always believe what you read: never hurts to read the original reference. PMID- 22777751 TI - Distinct patterns of gene expression in the superficial, middle and deep zones of bovine articular cartilage. AB - Hyaline articular cartilage will not heal spontaneously, and lesions in hyaline articular cartilage often result in degenerative joint disease. Considerable progress has been made with respect to the responsive stem cells, inductive signals and extracellular scaffolding required for the optimal regeneration of cartilage. However, many challenges remain, such as topographic differences in the functional zones of articular cartilage. We hypothesized that a distinct set of differentially expressed genes define the surface, middle and deep zones of hyaline articular cartilage. Microarray analysis of bovine articular cartilage from the superficial and middle zones revealed 52 genes differentially expressed >= 10-fold and 114 additional genes differentially expressed >= five-fold. However, no genes were identified with a >= five-fold difference in expression when comparing articular cartilage from the middle and deep zones. There are distinct, differential gene expression patterns in the superficial and middle zones of hyaline articular cartilage that highlight the functional differences between these zones. This investigation has implications for the tissue engineering and regeneration of hyaline articular cartilage. PMID- 22777752 TI - In vivo antigenotoxic potential and possible mechanism of action of selected 4 hydroxy-2H-chromen-2-one derivatives. AB - The in vivo sex-linked recessive lethal test was carried out in Drosophila melanogaster to investigate whether or not five substituted 4-hydroxy-2H-chromen 2-ones can modulate the genotoxicity of the well-established mutagenic agent ethyl methanesulfonate (EMS). For this purpose, 3 days old Canton S males were treated with the potent mutagen EMS alone in concentration of 0.75 ppm, as well as in combination with one of the five 4-hydroxycoumarins, namely diethyl 2-(1-(4 hydroxy-2-oxo-2H-chromen-3-yl)ethylidene)malonate (2b), 3-(1-(4-hydroxy-2-oxo-2H chromen-3-yl)ethylidene)pentane-2,4-dione (6b), 4-(4-(4-hydroxy-2-oxo-2H-chromen 3-yl)thiazol-2-ylamino) benzenesulfonic acid (4c), 4-hydroxy-3-(2-(2-nitropheny lamino)thiazol-4-yl)-2H-chromen-2-one (9c), and (E)-4-hydroxy-3-(1-(m tolylimino)ethyl)-2H-chromen-2-one (5d), in concentration of 70 ppm. The frequency of germinative mutations increased significantly after the treatment with EMS and decreased after treatments with coumarins. The maximum reduction was observed after treatments with 2b, 6b, 4c, and 5d. By the formation of hydrogen bonds or electrostatic interactions with O(6) of DNA guanine, tested coumarins prevent EMS-induced alkylation. The results indicate a protective role of five 4 hydroxycoumarins under the action of a strong mutagen. PMID- 22777753 TI - A simple confined impingement jets mixer for flash nanoprecipitation. AB - Johnson and Prud'homme (2003. AICHE J 49:2264-2282) introduced the confined impingement jets (CIJ) mixer to prepare nanoparticles loaded with hydrophobic compounds (e.g., drugs, inks, fragrances, or pheromones) via flash nanoprecipitation (FNP). We have modified the original CIJ design to allow hand operation, eliminating the need for a syringe pump, and we added a second antisolvent dilution stage. Impingement mixing requires equal flow momentum from two opposing jets, one containing the drug in organic solvent and the other containing an antisolvent, typically water. The subsequent dilution step in the new design allows rapid quenching with high antisolvent concentration that enhances nanoparticle stability. This new CIJ with dilution (CIJ-D) mixer is a simple, cheap, and efficient device to produce nanoparticles. We have made 55 nm diameter beta-carotene nanoparticles using the CIJ-D mixer. They are stable and reproducible in terms of particle size and distribution. We have also compared the performance of our CIJ-D mixer with the vortex mixer, which can operate at unequal flow rates (Liu et al., 2008. Chem Eng Sci 63:2829-2842), to make beta carotene-containing particles over a series of turbulent conditions. On the basis of dynamic light scattering measurements, the new CIJ-D mixer produces stable particles of a size similar to the vortex mixer. Our CIJ-D design requires less volume and provides an easily operated and inexpensive tool to produce nanoparticles via FNP and to evaluate new nanoparticle formulation. PMID- 22777754 TI - The forkhead transcription factor FoxY regulates Nanos. AB - FoxY is a member of the forkhead transcription factor family that appeared enriched in the presumptive germ line of sea urchins (Ransick et al. Dev Biol 2002;246:132). Here, we test the hypothesis that FoxY is involved in germ line determination in this animal. We found two splice forms of FoxY that share the same DNA-binding domain, but vary in the carboxy-terminal trans activation/repression domain. Both forms of the FoxY protein are present in the egg and in the early embryo, and their mRNAs accumulate to their highest levels in the small micromeres and adjacent non-skeletogenic mesoderm. Knockdown of FoxY resulted in a dramatic decrease in Nanos mRNA and protein levels as well as a loss of coelomic pouches in 2-week-old larvae. Our results indicate that FoxY positively regulates Nanos at the transcriptional level and is essential for reproductive potential in this organism. PMID- 22777755 TI - Template-directed synthesis in 3'- and 5'-direction with reversible termination. PMID- 22777756 TI - Ingestion of low-dose ibuprofen following resistance exercise in postmenopausal women. AB - BACKGROUND: Postmenopausal women typically experience accelerated muscle loss which has a negative effect on strength. The maximum daily recommended dosage of ibuprofen (1,200 mg) following resistance exercise has been shown to increase muscle hypertrophy and strength in older adults. This study aimed to determine the effects of low-dose ibuprofen (400 mg) immediately following resistance exercise sessions on muscle mass and strength in postmenopausal women. METHODS: Participants were randomized to ingest ibuprofen (IBU: n = 15, 57.8 +/- 5.1 years, 75.9 +/- 9.0 kg, 165.9 +/- 6.2 cm, BMI = 28 +/- 4 kg/m(2)) or placebo (PLA: n = 13, 56.5 +/- 4.4 years, 73.0 +/- 10.4 kg, 163.1 +/- 5.9 cm, BMI = 26 +/ 9 kg/m(2)) immediately following resistance exercise (11 whole-body exercises), which was performed 3 days/week, on nonconsecutive days, for 9 weeks. Prior to and following training, measures were taken for lean tissue mass (dual-energy X ray absorptiometry), muscle size of the elbow and knee flexors and extensors and ankle dorsiflexors and plantar flexors (ultrasound), and strength (one-repetition maximum leg press and chest press). RESULTS: Over the 9 weeks of training, there were significant changes (p < 0.05) in lean tissue mass (IBU, -1.1 +/- 1.0 kg; PLA, -0.7 +/- 1.4 kg), muscle size of the knee extensors (IBU, 0.3 +/- 0.6 cm; PLA, 0.2 +/- 0.7 cm), ankle dorsiflexors (IBU, 0.5 +/- 0.8 cm; PLA, 0.1 +/- 0.5 cm), and ankle plantar flexors (IBU, 0.3 +/- 0.9 cm; PLA, 0.5 +/- 0.9 cm), leg press strength (IBU, 20.6 +/- 18.0 kg; PLA, 20.0 +/- 20.0 kg), and chest press strength (IBU, 5.1 +/- 9.5 kg; PLA, 8.1 +/- 7.6 kg), with no differences between groups. CONCLUSION: Low-dose ibuprofen following resistance exercise has no greater effect on muscle mass or strength over exercise alone in postmenopausal women. PMID- 22777757 TI - Serum creatinine as a marker of muscle mass in chronic kidney disease: results of a cross-sectional study and review of literature. AB - BACKGROUND: Higher muscle mass is associated with better outcomes and longevity in patients with chronic disease states. Imaging studies such as dual-energy X ray absorptiometry (DEXA) are among the gold standard methods for assessing body fat and lean body mass (LBM), approximately half of which is comprised of skeletal muscle mass. Elaborate imaging devices, however, are not commonly available in routine clinical practice and therefore easily accessible and cost effective, but reliable muscle mass biomarkers are needed. One such marker is serum creatinine, derived from muscle-based creatine, which is inexpensive and ubiquitously available, and it can serve as a biomarker of skeletal muscle mass in human subjects. METHODS AND RESULTS: In 118 hemodialysis patients, we found that the 3-month averaged serum creatinine concentration correlated well with DEXA-measured LBM. The recent literature regarding serum creatinine as a surrogate of muscle mass is summarized, as is the literature concerning the use of other measures of muscle mass, such as plasma gelsolin and actin, and urinary creatinine excretion. We have also reviewed the role of dietary meat intake in serum creatinine variability along with several biomarkers of dietary meat intake (creatine, carnitine, carnosine, ophidine, anserine, 3-methyl-L-histidine and 1 methylhistidine). CONCLUSION: In summary, none of these biomarkers was studied in CKD patients. We advance the hypothesis that in both health and disease, under steady state, serum creatinine can serve as a reliable muscle mass biomarker if appropriate adjustment for full or residual kidney function and dietary meat intake is undertaken. PMID- 22777758 TI - High payload dual therapeutic-imaging nanocarriers for triggered tumor delivery. AB - The in vitro and in vivo characterization of an optimized formulation of nanoparticles (NPs) loaded with a high content of dexamethasone palmitate (DEX P), a chemotherapeutic adjuvant that decreases interstitial fluid pressure in tumors, and (111) In, a signaling agent, is described. These NPs are uniform in size and composition. Single photon emission computed tomography imaging demonstrates significant tumor uptake of (111) In-labeled DEX-P NPs in tumor bearing mice. As with many nanoparticle-based drug delivery systems, significant liver accumulation is observed. Assessment of liver histology and blood tests show no apparent hepatic or renal toxicity of the DEX-P NPs. Conversion of DEX-P to DEX occurs when DEX-P NPs are incubated with mouse plasma, human tumor homogenate and ascites from tumor bearing mice, but not with human plasma. This conversion is slower in plasma from Es1(e) ((-/-)) /SCID mice, a potential alternative animal model that better mimics humans; however, plasma from these mice are not completely devoid of esterase activity. The difference between blood and tumor esterase activity in humans facilitates the delivery of DEX-P NPs to tumors and the release of dexamethasone by an esterase trigger. PMID- 22777761 TI - Partial hydrolysis of poly(2-ethyl-2-oxazoline) and potential implications for biomedical applications? AB - The hydrolysis of PEtOx is studied to evaluate the potential toxicity of partially hydrolyzed polymers that might interfere with its increasing popularity for biomedical applications. The hydrolysis of PEtOx is studied in the presence of digestive enzymes (gastric and intestinal) and at 5.8 M hydrochloric acid as a function of temperature (57, 73, 90, and 100 degrees C). It is found that PEtOx undergoes negligible hydrolysis at 37 degrees C and that thermal and solution properties are not altered when up to 10% of the polymer backbone is hydrolyzed. Mucosal irritation and cytotoxicity is also absent up to 10% hydrolysis levels. In conclusion, PEtOx will not decompose at physiological conditions, and partial hydrolysis will not limit its biomedical applications. PMID- 22777759 TI - The CD8+ HLA-DR+ T cells expanded in HIV-1 infection are qualitatively identical to those from healthy controls. AB - HIV-induced immune activation leads to expansion of a subset of human CD8(+) T cells expressing HLA-DR antigens. Expansion of CD8(+) HLA-DR(+) T cells can be also observed in non-HIV settings including several autoimmune diseases and aging. Although these cells are felt to represent "immune exhaustion" and/or to be anergic, their precise role in host defense has remained unclear. Here, we report that this subset of cells exhibits a restricted repertoire, shows evidence of multiple rounds of division, but lacks markers of recent TCR engagement. Detailed cell cycle analysis revealed that compared with their CD8(+) HLA-DR(-) counterpart, the CD8(+) HLA-DR(+) T-cell pool contained an increased fraction of cells in S-phase with elevated levels of the G2/M regulators: cyclin A2, CDC25C, Cdc2 (CDK1), indicating that these cells are not truly anergic but rather experiencing proliferation in vivo. Together, these data support a hypothesis that antigen stimulation leads to the initial expansion of a CD8(+) pool of cells in vivo that undergo further expansion independent of ongoing TCR engagement. No qualitative differences were noted between CD8(+) HLA-DR(+) cells from HIV(+) and HIV(-) donors, indicating that the generation of CD8(+) HLA DR(+) T cells is a part of normal immune regulation that is exaggerated in the setting of HIV-1 infection. PMID- 22777760 TI - Isolation and characterization of mesenchymal stem cells from whole human umbilical cord applying a single enzyme approach. AB - Mesenchymal stem cells (MSCs) are multipotent cells traditionally derived from bone marrow (BM). They have been demonstrated to be widely applied in tissue regeneration and cellular therapy. As an alternative to BM, an umbilical cord (UC) is considered as a potential source of MSCs. Here, we showed that human UC MSCs were easily isolated by a single enzymatic digestion and characteristic of plastic adherence and fibroblast-like morphology. UC-MSCs isolation was successful in 15 of 15 samples. The colony-forming unit-fibroblast frequency was obtained 54 +/- 1.33 from 103 UC-MSCs at passage 3, and the doubling time was (24.15 +/- 0.49) h. Almost 1010 UC-MSCs were largely produced in about 30 days. By flow cytometry analysis, the adherent cells displayed an abundant presence of CD73, CD90 and CD105 and absence of CD34, CD45 and HLA-DR. When cultured in differentiation media, they can be differentiated into adipocytes, osteocytes and chondrocytes. RT-PCR reactions confirmed that their multidifferentiation related genes were positive. Moreover, stem cell-related transcription factors Nanog, Oct 4 and Sox-2 were positively expressed in UC-MSCs. On the basis of these findings, the single enzyme method is a good method to obtain large-scale production of MSCs from whole human UC in a short time, and the UC can be considered as a novel and convenient source of adult MSCs displaying high expansion potential and primitive pluripotent stem cells. PMID- 22777762 TI - Immobilization/stabilization of acid urease on Eupergit(r) supports. AB - The adsorption capacity and immobilization rate of two Eupergit(r) supports for acid urease was studied by varying the ionic strength and enzyme preparation concentration in the immobilizing solution at pH 7. Eupergit(r) C250 L yielded a series of derivatives with enzyme loadings (Y(P/B)) ranging from 48 to 171 mg of bovine serum albumin equivalent (BSAE) per gram of dry support (ds). Use of drastic postimmobilization conditions at pH 9 for 3-9 days yielded a slight decrease (8-14%) in the initial activity of immobilized enzymes and a limited increase in the stabilization factor (1.1-1.5), as assessed by accelerated aging tests at 65 degrees C. Further storage tests at 4 degrees C in the wet state showed that the activity of several derivatives either stabilized or not was practically constant for as long as 547 days. Both free enzyme and immobilized acid urease derivatives exhibited a kinetic pattern of the Michaelis-Menten type. Using the Eadie-Hofstee diagram, the specific ammonia formation rate constant for free (k(cat)) or immobilized (k'(cat)) enzyme resulted to be little affected by immobilization (k(cat) ~ k'(cat) ~ 18.86 +/- 0.34 IU/mg BSAE), whereas the apparent Michaelis constant for immobilized enzymes exhibited a statistically significant increase at P < 0.05 from the intrinsic value (2.55 +/- 0.14 mM) for free enzyme to 5.38 +/- 0.87 mM as Y(P/B) increased to 171 mg BSAE/g ds. By estimating the observable Thiele modulus (Phi(obs) ), the activity of the biocatalyst with the greatest enzyme loading at the lowest urea concentrations tested (0.833 mM) was reduced by a factor of about 2 due to internal diffusional limitations. By operating in the pseudofirst-order regime with immobilized derivatives at Y(P/B) about 126 mg BSAE/g ds, their activity after grinding was no more limited by intraparticle diffusion and approached the value for free enzyme. PMID- 22777763 TI - Introducing solid foods: validity of report among mothers who do not adhere to recommended US guidelines. AB - BACKGROUND: Introducing solids foods to infants before 6 months has been associated with adverse long-term health outcomes. Studies and surveys frequently use maternal report to identify the age when infants start solid foods. OBJECTIVE: To address the accuracy of maternal report at 1 year postpartum regarding introduction of solid foods. METHODS: Between 2008 and 2009, the authors enrolled mothers of healthy term singletons at an urban Boston hospital within 72 hours of giving birth. We called mothers monthly for 6 months and asked if they had given their baby solid foods in the previous month. At 1 year, we contacted mothers again and asked when they first gave solid foods; answers at 1 year were compared with the data collected monthly. RESULTS: The authors analyzed data on 157 women, all of whom had, according to monthly responses, started solid foods before 6 months. At 1 year, only 14% (22/157) of reports matched data recorded monthly. Although 100% of women introduced solids before 6 months, at 1 year, 41.4% reported starting solids at 6 months. CONCLUSIONS: Among women who started feeding solids before 6 months, most did not give an accurate response at 1 year. Most said they started giving solids later than they did. Maternal report may not be the best way to collect such data, and health outcomes based on such data may be biased toward the null. PMID- 22777764 TI - Multi-institutional evaluation of a sinus surgery checklist. AB - OBJECTIVES/HYPOTHESIS: To examine the frequency of safe surgical practices specific to endoscopic sinus surgery (ESS) before and after implementation of a checklist at four institutions across North America. STUDY DESIGN: Prospective, multi-institutional, observational study. METHODS: Consecutive surgeries were observed at four institutions before (n = 100) and after (n = 100) implementation of the ESS Checklist. A passive observer documented whether 10 specific tasks were performed by the surgical team during the course of each case. The frequency with which each item was performed was tabulated, and differences across institutions were evaluated using the Pearson chi(2) test. Improvement in the frequency of each single item between pre- and postintervention time periods was assessed by the McNemar chi(2) test. RESULTS: Successful performance of all 10 tasks in the prechecklist period was not observed for any ESS case at any of the four study sites. As might be expected, performance of any individual task was highly variable, ranging from 14% to 95%. After implementation of the ESS Checklist, successful performance of all 10 tasks during an individual surgery increased from 0% to 87% across all institutions, a change that was highly significant (P < .001). Significant increases in the performance of individual tasks was observed for nine of 10 items across all institutions (P <= .031 for all). CONCLUSIONS: Significant heterogeneity exists with regard to performance of specific tasks aimed at minimizing error during ESS. Utilization of the ESS Checklist standardized practice across four institutions and significantly increased the likelihood that individual safety tasks were performed during the course of sinus surgery. PMID- 22777765 TI - Regulation of lung fibroblast activation by annexin A1. AB - Annexin-A1 (AnxA1) is a glucocorticoid-induced protein with multiple actions in the regulation of inflammatory cell activation. The contribution of AnxA1 to human cell biology is not well understood. We investigated the contribution of AnxA1 and its receptor, formyl-peptide receptor 2 (FPR2), to the regulation of inflammatory responses in human normal lung fibroblasts (NLF). Silencing constitutive AnxA1 expression in NLF using small interfering RNA (siRNA) was associated with moderate but significant increases in tumor necrosis factor (TNF) induced proliferation and interleukin (IL)-6 production, accompanied by reduction of ERK and NF-kappaB activity. AnxA1 regulation of ERK and NF-kappaB activation was associated with effects on proliferation. Blocking FPR2 using the specific antagonist WRW4 mimicked the effects of AnxA1 silencing on TNF-induced proliferation, IL-6, ERK, and NF-kappaB activation. AnxA1 silencing also impaired inhibitory effects of glucocorticoid on IL-6 production and on the expression of glucocorticoid-induced leucine zipper (GILZ), but blocking FPR2 failed to mimic these effects of AnxA1 silencing. These data suggest that AnxA1 regulates TNF induced proliferation and inflammatory responses in lung fibroblasts, via effects on the ERK and NF-kappaB pathways, which depend on FPR2. AnxA1 also mediates effects of glucocorticoids and GILZ expression, but these effects appear independent of FPR2. These findings suggest that mimicking AnxA1 actions might have therapeutic potential in chronic inflammatory lung diseases. PMID- 22777766 TI - Abnormal conformation and impaired degradation of propylthiouracil-induced neutrophil extracellular traps: implications of disordered neutrophil extracellular traps in a rat model of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis. AB - OBJECTIVE: Neutrophil extracellular traps (NETs) are composed of DNA and antimicrobial proteins, including myeloperoxidase (MPO). Recent studies have demonstrated that impaired regulation of NETs could trigger an autoimmune response. Propylthiouracil (PTU), an antithyroid drug, is associated with a risk of MPO antineutrophil cytoplasmic antibody (ANCA) production and MPO ANCA associated vasculitis (MPO AAV). This study was undertaken to clarify the mechanism of MPO ANCA production, using the PTU-induced model of MPO AAV. METHODS: NETs were induced by treating human neutrophils with phorbol myristate acetate (PMA) in vitro. We examined whether the addition of PTU influenced the NET formation induced by PMA and the degradation of NETs by DNase I, which is regarded as a regulator of NETs. Furthermore, we examined whether NETs generated by the combination of PMA and PTU induced MPO ANCA and MPO AAV in vivo in rats. RESULTS: When NETs were induced by PMA with PTU using human neutrophils in vitro, abnormal conformation of NETs was observed. Interestingly, the abnormal NETs were hardly digested by DNase I. Moreover, rats immunized with the abnormal NETs, which had been induced by PMA with PTU using rat neutrophils, produced MPO ANCA and developed pulmonary capillaritis. When rats were given oral PTU with intraperitoneal injection of PMA, pauci-immune glomerulonephritis and pulmonary capillaritis occurred with MPO ANCA production in the serum. CONCLUSION: Our findings indicate that abnormal conformation and impaired degradation of NETs induced by PTU are involved in the pathogenesis of PTU-induced MPO ANCA production and MPO AAV. These findings suggest that disordered NETs can be critically implicated in the pathogenesis of MPO AAV. PMID- 22777767 TI - Can valved mitral prosthesis be implanted within all kinds of the mitral annuloplasty rings? PMID- 22777768 TI - CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues. AB - Although high mammographic density is considered one of the strongest risk factors for invasive breast cancer, the genes involved in modulating this clinical feature are unknown. Tissues of high mammographic density share key histologic features with stromal components within malignant lesions of tumor tissues, specifically low adipocyte and high extracellular matrix (ECM) content. We show that CD36, a transmembrane receptor that coordinately modulates multiple protumorigenic phenotypes, including adipocyte differentiation, angiogenesis, cell-ECM interactions, and immune signaling, is greatly repressed in multiple cell types of disease-free stroma associated with high mammographic density and tumor stroma. Using both in vitro and in vivo assays, we show that CD36 repression is necessary and sufficient to recapitulate the above-mentioned phenotypes observed in high mammographic density and tumor tissues. Consistent with a functional role for this coordinated program in tumorigenesis, we observe that clinical outcomes are strongly associated with CD36 expression. SIGNIFICANCE: CD36 simultaneously controls adipocyte content and matrix accumulation and is coordinately repressed in multiple cell types within tumor and high mammographic density stroma, suggesting that activation of this stromal program is an early event in tumorigenesis. Levels of CD36 and extent of mammographic density are both modifiable factors that provide potential for intervention. PMID- 22777770 TI - Improved burns therapy: liposomes-in-hydrogel delivery system for mupirocin. AB - Wounds, particularly burns, are prone to colonization of potentially life threatening bacteria. Local delivery of antimicrobial agents in sufficient quantities and over longer period of time can reduce risk of burn infections. Mupirocin-in-liposomes-in-hydrogels were proposed as advanced delivery system for improved burn therapy. Mupirocin was entrapped in phosphatidylcholine liposomes of various sizes, namely larger (micron size) vesicles entrapping 74% of drug and sonicated vesicles (below 300 nm) entrapping 49% of drug. Liposomes containing mupirocin were incorporated in chitosan hydrogels (10%, w/w). Incorporation of liposomes in hydrogels resulted in prolonged release of liposomally associated mupirocin, as observed in both in vitro and ex vivo studies. The drug release was affected by the vesicle size. Microbiological evaluation of newly developed system confirmed its antimicrobial potential against Staphylococcus aureus and Bacillus subtilis. Bioadhesiveness of the system was compared with the marketed cream containing mupirocin. Our system exhibited superior bioadhesiveness and sustained mupirocin release profiles to marketed product. PMID- 22777769 TI - VEGF/neuropilin-2 regulation of Bmi-1 and consequent repression of IGF-IR define a novel mechanism of aggressive prostate cancer. AB - We show that the VEGF receptor neuropilin-2 (NRP2) is associated with high-grade, PTEN-null prostate cancer and that its expression in tumor cells is induced by PTEN loss as a consequence of c-Jun activation. VEGF/NRP2 signaling represses insulin-like growth factor-1 receptor (IGF-IR) expression and signaling, and the mechanism involves Bmi-1-mediated transcriptional repression of the IGF-IR. This mechanism has significant functional and therapeutic implications that were evaluated. IGF-IR expression positively correlates with PTEN and inversely correlates with NRP2 in prostate tumors. NRP2 is a robust biomarker for predicting response to IGF-IR therapy because prostate carcinomas that express NRP2 exhibit low levels of IGF-IR. Conversely, targeting NRP2 is only modestly effective because NRP2 inhibition induces compensatory IGF-IR signaling. Inhibition of both NRP2 and IGF-IR, however, completely blocks tumor growth in vivo. PMID- 22777771 TI - Porous calcium phosphate cement for alveolar bone regeneration. AB - The present study aimed to provide information on material degradation and subsequent alveolar bone formation, using composites consisting of calcium phosphate cement (CPC) and poly(lactic-co-glycolic) acid (PLGA) with different microsphere morphology (hollow vs dense). In addition to the plain CPC-PLGA composites, loading the microspheres with the growth factors platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF) was investigated. A total of four different CPC composites were applied into one-wall mandible bone defects in beagle dogs in order to evaluate them as candidates for alveolar bone regeneration. These composites consisted of CPC and hollow or dense PLGA microspheres, with or without the addition of PDGF-IGF growth factor combination (CPC-hPLGA, CPC-dPLGA, CPC-hPLGAGF , CPC-dPLGAGF ). Histological evaluation revealed significantly more bone formation in CPC-dPLGA than in CPC-hPLGA composites. The combination PDGF-IGF enhanced bone formation in CPC-hPLGA materials, but significantly more bone formation occurred when CPC-dPLGA was used, with or without the addition of growth factors. The findings demonstrated that CPC-dPLGA composite was the biologically superior material for use as an off the-shelf material, due to its good biocompatibility, enhanced degradability and superior bone formation. PMID- 22777773 TI - How to write a paper for Rapid Communications in Mass Spectrometry. PMID- 22777772 TI - Hypoxia favors maintenance of the vascular smooth muscle cell phenotype in culture. PMID- 22777774 TI - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry combined with multidimensional scaling, binary hierarchical cluster tree and selected diagnostic masses improves species identification of Neolithic keratin sequences from furs of the Tyrolean Iceman Oetzi. AB - The identification of fur origins from the 5300-year-old Tyrolean Iceman's accoutrement is not yet complete, although definite identification is essential for the socio-cultural context of his epoch. Neither have all potential samples been identified so far, nor there has a consensus been reached on the species identified using the classical methods. Archaeological hair often lacks analyzable hair scale patterns in microscopic analyses and polymer chain reaction (PCR)-based techniques are often inapplicable due to the lack of amplifiable ancient DNA. To overcome these drawbacks, a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method was used exclusively based on hair keratins. Thirteen fur specimens from his accoutrement were analyzed after tryptic digest of native hair. Peptide mass fingerprints (pmfs) from ancient samples and from reference species mostly occurring in the Alpine surroundings at his lifetime were compared to each other using multidimensional scaling and binary hierarchical cluster tree analysis. Both statistical methods highly reflect spectral similarities among pmfs as close zoological relationships. While multidimensional scaling was useful to discriminate specimens on the zoological order level, binary hierarchical cluster tree reached the family or subfamily level. Additionally, the presence and/or absence of order, family and/or species-specific diagnostic masses in their pmfs allowed the identification of mammals mostly down to single species level. Red deer was found in his shoe vamp, goat in the leggings, cattle in his shoe sole and at his quiver's closing flap as well as sheep and chamois in his coat. Canid species, like grey wolf, domestic dog or European red fox, were discovered in his leggings for the first time, but could not be differentiated to species level. This is widening the spectrum of processed fur-bearing species to at least one member of the Canidae family. His fur cap was allocated to a carnivore species, but differentiation between brown bear and a canid species could not be made with certainty. PMID- 22777775 TI - Variation of compound-specific hydrogen isotope ratios under changing temperature program in gas chromatography/thermal conversion/isotope ratio mass spectrometry. AB - RATIONALE: In recent experiments, we found that compound-specific delta(2)H values can vary as a result of changing the gas chromatography temperature program under common pyrolysis conditions. To achieve better precision, it is necessary to examine the details and find a solution to this problem when using gas chromatography/thermal conversion/isotope ratio mass spectrometry (GC-TC IRMS) for hydrogen isotope analysis. METHODS: A test was designed to find the possible temperature effect under four different GC temperature ramp rates using n-alkanes (n-C(21), n-C(27), and n-C(31)) and fatty acids (n-C(12), n-C(18), and n-C(24)). The common 'hexane' method was used initially to condition the pyrolysis reactor. Experiments were then carried out using the 'methane condition' method because it was considered to improve pyrolysis efficiency. RESULTS: Under the 'hexane condition' the measured hydrogen isotope ratios of the n-alkanes and n-fatty acids became more positive with increasing GC temperature ramp rate. The ion current intensity of hydrogen also generally increased. However, when the 'methane condition' method was used, the measured delta(2)H values of the n-alkanes and n-fatty acids showed little change under different GC temperature ramp rates. CONCLUSIONS: Higher pyrolysis efficiency could reduce the tailing of the H(2) peak and the related isotopic variations at increased GC temperature ramp rates. In addition, too slow a temperature ramp rate could broaden the peak width and thus increase the background effect and possible isotopic fractionations in the split interface; this could also influence the hydrogen isotope values. We therefore suggest that the appropriate temperature ramp rate is an important factor in improving the precision in analyzing compound specific hydrogen isotopes. PMID- 22777776 TI - Carbon isotopic characterization of cider CO2 by isotope ratio mass spectrometry: a tool for quality and authenticity assessment. AB - RATIONALE: The cider market is an important sector of the food industry in certain regions. Adulteration of cider can happen in several ways: for example, by the addition of sugar, or of exogenous CO(2) to certain types of cider. Because such practices are not allowed by either Spanish legislation or the legislation of other countries, it is essential to study possible methods to detect these unauthorized practices. For this purpose a procedure was required to study the stable carbon isotopic composition of CO(2) in cider. METHODS: A liquid sample of cider was transferred to a vial and CO(2) from the headspace of the vial was analyzed using a peripheral device interfaced to an isotope ratio mass spectrometer. Separation of the CO(2) from water and ethanol was achieved using a gas chromatography column located in the peripheral device. RESULTS: The values for repeatability and reproducibility obtained indicated the robustness of the method, which is required for routine analysis. Ninety cider samples from various origins were analyzed, most of which showed a (13)C content consistent with the declared origin. The delta(13)C ranged from -24.800/00 to -20.890/00 for ciders with endogenous carbon dioxide (-22.74 +/- 0.790/00) and -37.130/00 to -26.000/00 if industrial CO(2) was added. Several samples were also suspected of C4 sugar addition prior to the fermentation. CONCLUSIONS: A fast, accurate and simple method for cider adulteration detection was developed. The addition of exogenous CO(2) as well as C4 sugar addition prior to fermentation could be detected. The method showed advantages over existing methods in term of simplicity (no sample preparation and very long-term stability of the sample), speed (less than 10 min/sample) and precision ((r <=0.32 and R <=0.42). PMID- 22777777 TI - Production and ionization energies of K(n)F (n = 2-6) clusters by thermal ionization mass spectrometry. AB - RATIONALE: The very small clusters of the type K(n)F are of particular importance since their first ionization energies (IEs) are lower than those of the alkali metal atoms. Theoretical calculation has demonstrated that this kind of cluster represents a potential 'building block' for cluster-assembly materials with unique structural, electronic, optical, magnetic, and thermodynamic properties. To date, however, there have been no experimental results on the IEs of K(n)F (n >2) clusters. METHOD: K(n)F (n = 2-6) clusters were produced by the evaporation of a solid potassium fluoride salt using a modified thermal ionization source of modified design, and mass selected by a magnetic sector mass spectrometer where their IEs were determined. RESULTS: Clusters K(n)F (n = 3-6) were detected for the first time. The order of the ion intensities was K(2)F(+)> > K(4)F(+)> > K(3)F(+)K(6)F(+)> K(5)F(+). The determined IEs were 3.99 +/- 0.20 eV for K(2)F, 4.16 +/- 0.20 eV for K(3)F, 4.27 +/- 0.20 eV for K(4)F, 4.22 +/- 0.20 eV for K(5)F, and 4.31 +/- 0.20 eV for K(6)F. The IEs of K(n)F increase slightly with the increase in potassium atom number from 2 to 6. We also observed that the presence of a fluorine atom leads to increasing ionization energy of bare metal potassium clusters. CONCLUSIONS: The modified thermal ionization source provides an efficient way of obtaining the fluorine-doped potassium clusters. These results also present experimental proof that K(n)F (n = 2-6) clusters belong to the group of 'superalkali' species. PMID- 22777779 TI - Elimination of nitrogen interference during online oxygen isotope analysis of nitrogen-doped organics using the "NiCat" nickel reduction system. AB - RATIONALE: Accurate online analysis of the delta(18)O values of nitrogen-bearing organic compounds is of interest to several emergent fields, including ecology, forensics and paleontology. During online analysis, high-temperature conversion (HTC) of nitrogen-bearing organics produces N(2) gas which creates isobaric interference with the isotopic measurement. Specifically, N(2) reacts with trace amounts of oxygen in the mass spectrometer source to form (14)N(16)O (m/z 30), which prevents accurate evaluation of the sample (12)C(18)O peak (m/z 30). METHODS: We present an alternative system to the conventional HTC, which uses a nickel-catalyzed ("NiCat") reduction furnace to convert HTC-produced CO into CO(2), allowing for delta(18)O measurement using signal intensities at m/z 44 and 46. RESULTS: This system yields identical delta(18)O values for nitrogen-doped and undoped sucrose and cellulose compounds up to molar yield ratios of N(2):CO = 0.22. In contrast, our conventional HTC system configured to factory recommendations with the stock gas chromatography (GC) column produced a discrepancy of ~50/00 between nitrogen-doped and undoped samples. CONCLUSIONS: Because of its ability to eliminate isobaric interference, the NiCat system is a viable alternative to conventional HTC for delta(18)O measurement, and can be constructed from relatively inexpensive and readily available materials. As an additional advantage, the CO(2) analyte produced by NiCat may be cryofocused, to allow for oxygen-isotope determinations on very small amounts of sample substrate. PMID- 22777778 TI - Tandem mass spectrometry of bilin tetrapyrroles by electrospray ionization and collision-induced dissociation. AB - RATIONALE: Bilins are metabolic products of hosts and bacteria on porphyrins, and are markers of health state and human waste contamination. Although bilin tandem mass spectrometry reports exist, their fragmentation behavior as a function of structure has not been compared, nor has fragmentation been examined as a function of collision energy. METHODS: The fragmentation of bilins generated by positive ion mode electrospray ionization is examined by collision-induced dissociation (CID). CID on a quadrupole ion trap and on a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer as a function of collision energy is compared. Methyl esterification was used to deduce which product ions contain the inner pyrrole rings. FT-ICR high mass accuracy measurements were used to determine the formulas of the resultant product ions. RESULTS: The central carbon's bonding to the inner pyrrole rings influences fragmentation. Bilirubin is unique because fragmentation adjacent to the central methylene group between innermost rings predominates, and loss of a terminal pyrrole is observed only with helium collision gas. The other bilins lose the terminal pyrroles first; as CID energy is increased, additional fragmentation due to neutral losses of small molecules such as H(2)O, CO, CO(2), and methanol occurs. CONCLUSIONS: Based on these observations, fragmentation schemes for the bilins are proposed that are strongly dependent on the molecular structure and collision energy; only bilirubin fragmentation is influenced significantly by the collision gas used. This report should have value in identification of this class of molecules for biomarker detection. PMID- 22777781 TI - Elucidation of the mass fragmentation pathways of the polyether marine toxins, dinophysistoxins, and identification of isomer discrimination processes. AB - RATIONALE: Most of the liquid chromatography/mass spectrometry (LC/MS) methods that have been developed for the analysis of Diarrhetic Shellfish Poisoning (DSP) toxins in shellfish and algae samples have been unable to differentiate the isomers okadaic acid (OA) and dinophysistoxin-2 (DTX2), unless separated by chromatography. Since there are many bioconversion products of these compounds it is imperative to determine characteristic product ions, which can provide unequivocal identification of OA and DTX2 and their analogs. METHODS: Using electrospray ionization, the fragmentation processes for two types of precursor ions, [M+Na](+) and [M-H](-), of the polyether marine toxins, dinophysistoxins (DTXs), were studied using a hybrid linear ion trap Orbitrap mass spectrometer which provided high mass accuracy data in combination with multiple tandem mass (MS(n)) spectra. Three structurally related toxins were compared; okadaic acid (OA), dinophysistoxin-2 (DTX2) and dinophysistoxin-1 (DTX1). A quick multiple reaction monitoring (MRM) LC/MS/MS method was developed utilizing the characteristic precursor/product ion mass transitions. RESULTS: Comparison of the high-resolution product ion, [M-H](-), spectra of these toxins featured dominant signals that resulted from two six-centered rearrangements and previously proposed fragmentation pathways for the ion of m/z 321 and 293 have been corrected and identified. By contrast, the [M+Na](+) product ion spectra only revealed distinctive ions for the isomers, OA (m/z 595, 443 and 151) and DTX2 (m/z 581, 429 and 165). To illustrate the benefits of this study, a mass selective LC/MS/MS method was developed in which the isomers OA and DTX2 co eluted but were distinguished using the mass transitions, m/z 827/595, 827/443 (OA) and m/z 827/581, 827/429 (DTX2). CONCLUSIONS: Comparison of OA, DTX2 and DTX1 led to the correction of proposed negative ion mode fragmentation pathways. Through extensive study and comparison of the [M+Na](+) product ion spectra, distinctive product ions were identified which allowed for these compounds to be identified and distinguished without separation for the first time. PMID- 22777780 TI - The role of conformational flexibility in beta2-microglobulin amyloid fibril formation at neutral pH. AB - RATIONALE: Amyloid formation is implicated in a number of human diseases. beta(2) Microglobulin (beta(2)m) is the precursor protein in dialysis-related amyloidosis and it has been shown that partial, or more complete, unfolding is key to amyloid fibril formation in this pathology. Here the relationship between conformational flexibility and beta(2)m amyloid formation at physiological pH has been investigated. METHODS: HDX-ESI-MS was used to study the conformational dynamics of beta(2)m. Protein engineering, or the addition of Cu(2+) ions, sodium dodecyl sulphate, trifluoroethanol, heparin, or protein stabilisers, was employed to perturb the conformational dynamics of beta(2)m. The fibril-forming propensities of the protein variants and the wild-type protein in the presence of additives, which resulted in >5-fold increase in the EX1 rate of HDX, were investigated further. RESULTS: ESI-MS revealed that HDX occurs via a mixed EX1/EX2 mechanism under all conditions. Urea denaturation and tryptophan fluorescence indicated that EX1 exchange occurred from a globally unfolded state in wild-type beta(2)m. Although >30-fold increase in the HDX exchange rate was observed both for the protein variants and for the wild-type protein in the presence of specific additives, large increases in exchange rate did not necessarily result in extensive de novo fibril formation. CONCLUSIONS: The conformational dynamics measured by the EX1 rate of HDX do not predict the ability of beta(2)m to form amyloid fibrils de novo at neutral pH. This suggests that the formation of amyloid fibrils from beta(2)m at neutral pH is dependent on the generation of one or more specific aggregation-competent species which facilitate self-assembly. PMID- 22777782 TI - Investigation of non-covalent interaction of natural flexible cyclic molecules with telomeric RNA G-quadruplexes by electrospray ionization mass spectrometry. AB - RATIONALE: Recently, human telomeric DNA was found to be transcribed into RNA transcripts composing of tandem repeats of r(UUAGGG) which can form G-quadruplex structures. Studies have shown that human telomeric RNA is associated with the telomerase activity in vitro. Finding high affinity small molecule ligands binding to the telomeric RNA G-quadruplex may facilitate the regulation of the telomerase activity. METHODS: The 12-mer and 24-mer telomeric RNA sequences, r(UAGGGUUAGGGU) and r(UAGGGUUAGGGUUAGGGUUAGGGU), were synthesized by TaKaRa Biotechnology (Dalian) Co., Ltd. (TaKaRa, Dalian) with high-performance liquid chromatography (HPLC) purification. Electrospray ionization ion-trap mass spectrometry was used to evaluate the binding affinities of three natural flexible cyclic molecules, tetrandrine, fangchinoline and cepharanthine, with the telomeric RNA G-quadruplexes. The fragmentation pathways of the G-quadruplexes and G-quadruplex-ligand complexes were investigated by tandem mass spectrometry. RESULTS: the natural flexible cyclic molecules were found to have high binding affinities to the 12-mer and 24-mer RNA G-quadruplexes with stoichiometry of 1:1 to 3:1. Collision-induced dissociation tandem mass spectrometry shows that the G quadruplex-ligand complexes lose neutral ammoniums first and the small molecule ligand subsequently. Besides, among the three flexible cyclic molecules, cepharanthine binds most tightly to the RNA G-quadruplexes than tetandrine and fangchinoline. CONCLUSIONS: Three flexible cyclic small molecules were found to be potential telomeric RNA G-quadruplex ligands, especially cepharanthine, which has high affinity and binds most tightly to the RNA G-quadruplexes. These findings may provide further implications in the regulation of telomeric RNA and telomerase activity. PMID- 22777784 TI - In vivo metabolic investigation of moxifloxacin using liquid chromatography/electrospray ionization tandem mass spectrometry in combination with online hydrogen/deuterium exchange experiments. AB - RATIONALE: Tuberculosis is a leading cause of death from an infectious disease and moxifloxacin is an effective drug as compared to other fluoroquinolones. To date only two metabolites of the drug are known. Therefore, the present study on characterization of hitherto unknown in vivo metabolites of moxifloxacin using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI MS/MS) is undertaken. METHODS: In vivo metabolites of moxifloxacin have been identified and characterized by using LC/ESI-MS/MS in combination with an online hydrogen/deuterium (H/D) exchange technique. To identify in vivo metabolites, blood, urine and faeces samples were collected after oral administration of moxifloxacin to Sprague-Dawley rats. The samples were prepared using an optimized sample preparation approach involving protein precipitation, liquid-liquid extraction followed by solid-phase extraction and LC/MS/MS analysis. RESULTS: A total of nine phase I and ten phase II metabolites of moxifloxacin have been identified in urine samples including N-sulphated, glucuronide and hydroxylated metabolites which are also observed in plasma samples. In faeces samples, only the N-sulphated metabolite is observed. The structures of metabolites have been elucidated based on fragmentation patterns, accurate mass measurements and online H/D exchange LC/MS/MS experiments. Online H/D exchange experiments are used to support the identification and structural characterization of drug metabolites. CONCLUSIONS: A total of 19 in vivo metabolites of moxifloxacin have been characterized using LC/ESI-MS/MS in combination with accurate mass measurements and online H/D exchange experiments. The main phase I metabolites of moxifloxacin are hydroxylated, decarbonylated, desmethylated and desmethylhydroxylated metabolites which undergo subsequent phase II glucuronidation pathways. PMID- 22777783 TI - Migrating components in a polyurethane laminating adhesive identified using gas chromatography/mass spectrometry. AB - RATIONALE: Plastics are increasingly used as packaging materials for pharmaceuticals. However, diffusion of compounds in plastic into drugs may endanger patients' health. Regulatory authorities therefore demand detailed information about leachable compounds in plastics. Here we identify migrating components of a sterilization-resistant polyurethane (PUR) adhesive used in the primary packaging for an aqueous pharmaceutical. This identification is an essential first step for quantification and toxicological evaluation of the compounds. METHODS: We used various hyphenated mass spectrometry (MS) methods: gas chromatography (GC/MS) with either electron impact ionization or chemical ionization, and high resolution liquid chromatography (LC/MS) with electrospray ionization. RESULTS: Of the 13 migrating substances detected, 11 are cyclic esters with characteristic fragmentation schemes apparent from their mass spectra. These esters are formed as by-products during the reaction of adipic and isophthalic acid with monoethylene glycol and diethyelene glycol. A cyclic ester of isophthalic acid and tetraethylene glycol and a product of the reaction of isophoron diisocyanate with methanol were clearly identified. CONCLUSIONS: Complementary use of several hyphenated mass spectrometric methods enables successful identification of leachable compounds in the PUR adhesive under study. This opens the way for quantification and evaluation of the potential toxicities of these compounds. Despite the range of compositions of PUR laminates, the approach presented here may be applicable for the qualitative assessment of all PURs. PMID- 22777785 TI - Backbone fragmentations of [M-H]- anions from peptides. Reinvestigation of the mechanism of the beta prime cleavage. AB - RATIONALE: An experimental study has shown that the structure of a beta' ion proposed earlier is incorrect. Backbone cleavage beta' anions have structures R(NH(-)) from systems [[RNHCH(X)CONHCH(Y)CO(2)H (or C-terminal CONH(2))-H](-) (where R is the rest of the peptide molecule and X and Y represent the alpha side chains of the individual amino acid residues). METHODS: Ab initio calculations were carried out at the CAM-B3LYP/6-311++g(d,p) level of theory. CONCLUSIONS: The calculations suggest that RNH(-) ions are formed by S(N)i cyclisation processes involving either (i) the C-terminal CO(2)(-) or C-terminal [CONH](-) as appropriate, or (ii) an enolate ion [-NHC(-)(Y)-] cyclising at the backbone CH of the -CH(X)- group. Concomitant C-N bond cleavage then liberates an RNH(-) ion, processes which can occur along the peptide backbone. PMID- 22777786 TI - Determination of hazardous volatile organic compounds in the Hoffmann list by ion molecule reaction mass spectrometry. AB - RATIONALE: Off-line gas or liquid chromatographic mass spectrometry techniques are the most widely used method for analysis of hazardous, carcinogenic volatile organic compounds (VOCs) in mainstream cigarette smoke. However, these conventional techniques can lead to modification of VOCs during sample preparation due to the high reactivity of VOCs. Thus, the development of on-line mass spectrometric methods for analysis of VOCs is desirable to circumvent this problem. METHODS: The accurate identification of VOCs is a critical step in the analysis of cigarette smoke. Here, we use ion-molecule reaction mass spectrometry (IMR-MS) to study the behavior of standard VOCs in the Hoffmann list during this analytical procedure, and then to profile the VOCs in mainstream cigarette smoke using this on-line mass spectrometric method. RESULTS: We first discuss and summarize the charge transfer (CT) ionization and further fragmentation of 20 standard VOCs in the Hoffmann list with the ion reagents Hg(+), Xe(+), and Kr(+). The IMR-MS instrument was then connected to a Borgwaldt-RM20H rotary smoking machine in order to study VOCs in mainstream cigarette smoke on-line. Using this procedure, more than 20 VOCs were identified by IMR-MS by comparison with experimental results obtained on standard VOCs. CONCLUSIONS: The IMR-MS technique can potentially result in reduced molecular fragmentation during analysis of VOCs. However, significant fragmentation still occurs during IMR-MS when the ionization energy (IE) of the ion reagent is much higher than the IE of the VOC, given that excess energy is stored in the newly formed ion during CT ionization. Given that IMR-MS cannot distinguish between isobaric compounds or isomers, we summarize the possible overlapping mass peaks from these isobaric species that may be present in analyses of VOCs. Selection of the ion reagent for IMR-MS should be based on the need to ensure CT ionization of the analytes, as well as avoiding their severe fragmentation. PMID- 22777787 TI - Platinum vapor deposition surface-assisted laser desorption/ionization for imaging mass spectrometry of small molecules. AB - RATIONALE: Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) allows for the simultaneous detection and imaging of several molecules in a sample. However, when using an organic matrix in the MALDI-IMS of small molecules, inhomogeneous matrix crystallization may yield poorly reproducible peaks in the mass spectra. We describe a solvent-free approach that employs a homogeneously deposited metal nanoparticle layer (or film) for small molecule detection. METHODS: Platinum vapor deposition surface-assisted laser desorption/ionization imaging mass spectrometry (Pt vapor deposition SALDI-IMS) of small molecules was performed as a solvent-free and organic-matrix-free method. A commercially available magnetron sputtering device was used for Pt deposition. Vapor deposition of Pt produced a homogenous layer of nanoparticles over the surface of the target imaging sample. RESULTS: The effectiveness of Pt vapor deposition SALDI-IMS was demonstrated for the direct detection of small analytes of inkjet ink on printed paper as well as for various other analytes (saccharides, pigments, and drugs) separated by thin-layer chromatography (TLC), without the need for extraction or concentration processes. The advantage of choosing Pt instead of Au in SALDI-IMS was also shown. CONCLUSIONS: A solvent free approach involving the direct deposition of Pt on samples (SALDI-IMS) is effective for the analysis of inkjet-printed papers and various analytes separated by TLC. This method would be useful in imaging analyses of various insulating materials such as polymers and biological materials. PMID- 22777788 TI - Direct analysis in real time mass spectrometry for the rapid identification of four highly hazardous pesticides in agrochemicals. AB - RATIONALE: Direct analysis in real time (DART) is a new ion source technique, which is conducted in the open air under ambient conditions, applied to the rapid and direct analysis of any material (gases, liquids, and solids) with minimal or no sample preparation. In order to take advantage of the capacity of DART mass spectrometry for the real-time analysis of hazardous ingredients in commercial agrochemicals, a pilot study of rapid qualitative determination of hazardous pesticides was performed. METHODS: Highly hazardous pesticides were identified by DART ionization coupled to a single-quadrupole mass spectrometer (DART-MS). Acetonitrile was chosen for dissolving samples prior to the analysis. Samples were analyzed by this technique in as little as 5 s. RESULTS: Phorate, carbofuran, ethoprophos and fipronil were be detected directly from commercial agrochemicals. The ionization-related parameters (DART temperature, grid voltage and MS fragment) of these compounds were optimized to obtain highly response. Isotope patterns were taken into consideration for qualitative identification. Relative standard deviations (RSDs, n = 5) of 2.3-15.0% were obtained by measuring the relative abundance of selected isotopes. CONCLUSIONS: This study showed that DART-MS technology was able to qualitatively determine the existence of highly hazardous pesticides in commercial pesticide formulations. It is suggested that this technology should be applied for routine monitoring in the market. PMID- 22777789 TI - Studies in search of selective detection of isomeric biogenic hexen-1-ols and hexanal by flowing afterglow tandem mass spectrometry using [H3O]+ and [NO]+ reagent ions. AB - RATIONALE: Plants emit a blend of oxygenated volatile C(6) compounds, known as green leaf volatiles (GLVs), in response to leaf tissue damage related to stress conditions. On-line chemical ionization mass spectrometry (CI-MS) techniques have often been used to study the dynamics of these emissions but they fail to selectively detect some important GLV compounds. METHODS: A flowing afterglow tandem mass spectrometer (FA-TMS) was used to investigate the feasibility of selective on-line detection of isomeric hexen-1-ols and hexanal. Product ions at m/z 101 and 83 from chemical ionization (CI) of these compounds by [H(3)O](+), and product ions at m/z 100, 99, 83, 82 and 72 from CI by [NO](+), have been subjected to collision-induced dissociation (CID) in the collision cell of the TMS at center-of-mass energies ranging between 0 and 9 eV. RESULTS: CID of product ions at m/z 101 and 83 from CI of GLVs with [H(3)O](+) and of product ions at m/z 83, 82 and 72 from CI of GLVs with [NO](+) resulted in identical fragmentation patterns for all measured compounds, ruling out any selectivity. However, CID of product ions at m/z 100 and 99 from CI by [NO](+) led to CID product ions with abundances differing largely between the compounds, allowing the fast selective detection of 2-hexen-1-ols, 3-hexen-1-ols and hexanal with a chosen accuracy within a well-defined range of relative concentrations. CONCLUSIONS: This research illustrates that, in contrast to common CI-MS techniques, FA-TMS allows the selective detection of hexanal in a mixture of hexanal and hexen-1-ols with a chosen accuracy for a well-defined range of relative concentrations and represents a step forward in the search for selective detection of GLVs in CI-TMS. PMID- 22777790 TI - Determination of monoisotopic masses of chimera spectra from high-resolution mass spectrometric data by use of isotopic peak intensity ratio modeling. AB - RATIONALE: Chimera spectra make it challenging to identify proteins in complex mixtures by LC/MS/MS. Approximately half of the spectra collected are chimera spectra even when high-resolution tandem mass spectrometry is used. Chimera spectra are generated from the co-fragmentation of different co-elute peptides, and it is often difficult to distinguish monoisotopic precursors of these peptides from each other. METHODS: In this paper, we propose a peak intensity ratio-based monoisotopic peak determination algorithm (PIRMD) to distinguish different monoisotopic precursors of chimera spectra. Monoisotopic peaks in non overlapping clusters are detected by the edge features of the isotopic peak intensity ratios. For multiple overlapping clusters grouped as one cluster, monoisotopic peaks can be detected by an advanced estimation of the similarity between the estimated and the experimental isotopic distribution based on the isotopic peak intensity ratios. RESULTS: High-resolution mass spectrometric datasets acquired from mixtures of 30 synthetic peptides and mixtures of 18 proteins were used to evaluate the efficiency and accuracy of PIRMD. The results indicate that PIRMD can recognize monoisotopic precursors from the chimera spectra containing non-overlapping and overlapping isotopic clusters. Compared to several published algorithms, PIRMD identifies approximately 2 ~ 14% more spectra and has fewer false positives. CONCLUSIONS: The results on standard datasets and actual samples demonstrated that PIRMD could notably improve the successful identification rates of the spectra by identifying more chimera spectra, and of the identified spectra, approximately 25% are chimera spectra. This novel algorithm will help to interpret spectra produced by shotgun strategy in proteomics. PMID- 22777791 TI - Rapid differentiation of nucleotide phosphoramidate diastereomers by electrospray ionization tandem mass spectrometry. AB - RATIONALE: Nucleotide phosphoramidates are prodrugs which effectively deliver the active nucleotide to target tissues. It was shown that the individual phosphoramidate diastereomers have different antiviral activity, although the active nucleotide is the same. Therefore, a fast and simple analytical method is needed to characterize the individual diastereomeric phosphoramidate prodrugs. METHODS: Stock solutions of diastereomeric nucleotide phosphoramidate prodrugs, i.e., 5'-phosphate derivatives of the beta-D-2'-deoxy-2'-alpha-fluoro-2'-beta-C methyluridine nucleotide, were made in 25% acetonitrile to achieve a final concentration of 10 ug/mL. The samples were studied using high-performance liquid chromatography (HPLC) coupled with electrospray ionization tandem mass spectrometry (ESI-MS/MS). RESULTS: The MS/MS spectra of diastereomeric pairs showed substantial differences in the relative abundances of a characteristic ion in negative mode, which is proposed to be a cyclic phosphoramidate ion. Results were confirmed by the MS/MS spectrum of an analog without the NH proton and deuterium exchange experiment. Furthermore, the diastereomer-specific fragmentation behavior in negative ESI-MS was used to characterize a series of nucleotide phosphoramidates with different amino acid and aromatic substituents. CONCLUSIONS: An HPLC/MS/MS method was developed for the differentiation of the diastereomers of phosphoramidate prodrugs. In negative mode MS/MS spectra, the cyclic phosphoramidate ions yielded unambiguous distinction. This method presented a rapid and simple way for the characterization of nucleotide phosphoramidates. PMID- 22777792 TI - Effect of birth season on longevity: thrifty and hopeful phenotypes in historical Quebec. AB - OBJECTIVES: Individuals with fetal growth restrictions may become unhealthy as adult if they live in a nutritionally rich environment. Yet, there is little evidence for the counterpart that profuse resources during early development may prove detrimental in an impoverished adult environment. Using birth season as a proxy for nutrition in utero, this study tests whether early life effects on longevity are conditional on the environment in which people reside during adulthood. METHODS: I used Cox proportional hazard models of mortality after the age of 60 years among historical cohorts of French Canadian women born before 1750. Models are stratified by siblings to adjust the results for unobserved factors shared by family members. RESULTS: A birth during winter conferred the best-survival prospects in the south of the Saint-Lawrence River but the worse prospects in the north, where a birth during the fall was associated with the lowest mortality. Women who migrated to live on the other side of the river lost whatever advantage or disadvantage they had from their birth season and faced increases or decreases in risk that were specific to their new location. CONCLUSIONS: Based on Hales and Barker's thrifty phenotype hypothesis, and adding the "hopeful phenotype" counterpart, this study suggests that cues from the external environment during development are highly specific to that environment and that the slightest change of location may affect the chances for survival into old age. I finally address the role of fertility as a possible mediator or modifier of the effect of birth season on longevity. PMID- 22777793 TI - Multidimensional solid-state NMR studies of the structure and dynamics of pectic polysaccharides in uniformly 13C-labeled Arabidopsis primary cell walls. AB - Plant cell wall (CW) polysaccharides are responsible for the mechanical strength and growth of plant cells; however, the high-resolution structure and dynamics of the CW polysaccharides are still poorly understood because of the insoluble nature of these molecules. Here, we use 2D and 3D magic-angle-spinning (MAS) solid-state NMR (SSNMR) to investigate the structural role of pectins in the plant CW. Intact and partially depectinated primary CWs of Arabidopsis thaliana were uniformly labeled with (13)C and their NMR spectra were compared. Recent (13)C resonance assignment of the major polysaccharides in Arabidopsis thaliana CWs allowed us to determine the effects of depectination on the intermolecular packing and dynamics of the remaining wall polysaccharides. 2D and 3D correlation spectra show the suppression of pectin signals, confirming partial pectin removal by chelating agents and sodium carbonate. Importantly, higher cross peaks are observed in 2D and 3D (13)C spectra of the depectinated CW, suggesting higher rigidity and denser packing of the remaining wall polysaccharides compared with the intact CW. (13)C spin-lattice relaxation times and (1)H rotating-frame spin lattice relaxation times indicate that the polysaccharides are more rigid on both the nanosecond and microsecond timescales in the depectinated CW. Taken together, these results indicate that pectic polysaccharides are highly dynamic and endow the polysaccharide network of the primary CW with mobility and flexibility, which may be important for pectin functions. This study demonstrates the capability of multidimensional SSNMR to determine the intermolecular interactions and dynamic structures of complex plant materials under near-native conditions. PMID- 22777794 TI - Encapsulation of self-healing agents in polymer nanocapsules. PMID- 22777795 TI - Functional mesoporous silica nanoparticles for photothermal-controlled drug delivery in vivo. PMID- 22777796 TI - Expansion of follicular helper T cells in the absence of Treg cells: implications for loss of B-cell anergy. AB - The maintenance of B-cell anergy is essential to prevent the production of autoantibodies and autoimmunity. However, B-cell extrinsic mechanisms that regulate B-cell anergy remain poorly understood. We previously demonstrated that regulatory T (Treg) cells are necessary for the maintenance of B-cell anergy. We now show that in Treg-cell-deficient mice, helper T cells are necessary and sufficient for loss of B-cell tolerance/anergy. In addition, we show that the absence of Treg cells is associated with an increase in the proportion of CD4(+) cells that express GL7 and correlated with an increase in germinal center follicular helper T (GC-T(FH) ) cells. These GC-T(FH) cells, but not those from Treg-cell-sufficient hosts, were sufficient to drive antibody production by anergic B cells. We propose that a function of Treg cells is to prevent the expansion of T(FH) cells, especially GC-T(FH) cells, which support autoantibody production. PMID- 22777797 TI - Endolymphatic sac tumor and angiomatous lesions of the nasal and pharyngeal mucosa as a first manifestation of von Hippel-Lindau disease. AB - In the present article we report an endolymphatic sac tumor in a 15-year-old male who had additional angiomatous lesions in the nasal and pharyngeal mucosa and was diagnosed with von Hippel-Lindau disease postoperatively. Preoperative imaging excluded cholesteatoma, but did not provide sufficient information to distinguish between jugular paraganglioma and endolymphatic sac tumor. To the authors' knowledge this is the first description of angiomatous lesions in the mucosa of the upper respiratory tract in a von Hippel-Lindau disease patient, a potentially useful finding for future radiological differential diagnosis in cases presenting with endolymphatic sac tumor. PMID- 22777798 TI - Eroding the boundaries of cognition: implications of embodiment(1). AB - To accept that cognition is embodied is to question many of the beliefs traditionally held by cognitive scientists. One key question regards the localization of cognitive faculties. Here we argue that for cognition to be embodied and sometimes embedded, means that the cognitive faculty cannot be localized in a brain area alone. We review recent research on neural reuse, the 1/f structure of human activity, tool use, group cognition, and social coordination dynamics that we believe demonstrates how the boundary between the different areas of the brain, the brain and body, and the body and environment is not only blurred but indeterminate. In turn, we propose that cognition is supported by a nested structure of task-specific synergies, which are softly assembled from a variety of neural, bodily, and environmental components (including other individuals), and exhibit interaction dominant dynamics. PMID- 22777799 TI - Drug-related problems and factors influencing acceptance of clinical pharmacologists' alerts in a large cohort of neurology inpatients. AB - QUESTIONS UNDER STUDY/PRINCIPLES: Data regarding the prevalence and types of drug related problems (DRPs) among neurology inpatients is sparse. The objective of this study was to characterise the types of DRPs seen among neurology inpatients and furthermore to study factors affecting the acceptance of clinical pharmacologists' and pharmacists' recommendations for improving drug safety. METHODS: 1,263 consecutive inpatient cases in a Swiss university hospital neurology unit were assessed for the presence of DRPs over 12 months. Treating neurologists' acceptance of the resulting recommendations was also recorded. Primary outcome measures were types of DRP, recommendations made by clinical pharmacologists and number of recommendations accepted. Factors potentially associated with acceptance were studied using univariate and multivariate generalised estimating equation modelling. RESULTS: Twenty-nine percent of cases demonstrated one or more DRPs. DRPs were the cause of admission in 10 cases (0.8%). In total 494 DRPs were identified and 467 recommendations given, of which 62% were accepted. Factors associated with an increased likelihood of acceptance were prescriptions involving regularly administered drugs (odds ratio [OR] 2.57 95% confidence interval [CI] 1.73-3.80), adverse drug events (OR 2.5; 95% CI 1.29 5.06), known drug side-effect (OR 1.85; 95% CI 1.06-3.22), high-risk drug-drug interactions (OR 3.22; 95% CI 1.07-9.69) and interventions involving changing a drug (OR 2.71; 95% CI 1.17-6.25). CONCLUSION: Clinical pharmacologists and pharmacists can play an important role in identifying DRPs among neurology inpatients. Their recommendations for optimising medication-safety are most likely to be accepted for regular prescriptions, prescriptions associated with an adverse drug event and high-risk drug combinations. PMID- 22777800 TI - Modulation of macrophage activation and programming in immunity. AB - Macrophages are central mediators of the immune, contributing both to the initiation and the resolution of inflammation. The concept of macrophage activation and program has stimulated interest in its definition, and functional significance in homeostasis and diseases. It has been known that macrophages could be differently activated and programmed into different functional subtypes in response to different types of antigen stumuli or different kinds of cytokines present in the microenvironment and could thus profoundly influence immune responses, but little is known about the state and exact regulatory mechanism of macrophage activation and program from cell or molecular signaling level in immunity. In this review, we summarize the recent finding regarding the regulatory mechanism of macrophage activation and program toward M1 and M2, especially on M2 macrophages. PMID- 22777801 TI - Randomized clinical trial of ultrasound-guided foam sclerotherapy versus surgery for the incompetent great saphenous vein (Br J Surg 2012; 99: 1062-1070). PMID- 22777802 TI - Loss of the nerve monitoring signal during bilateral thyroid surgery (Br J Surg 2012; 99: 1089-1095). PMID- 22777804 TI - Recruiting patients into randomized clinical trials in surgery (Br J Surg 2012; 99: 307-308). PMID- 22777803 TI - Comparison of 30-day, 90-day and in-hospital postoperative mortality for eight cancer sites (Br J Surg 2012; 99: 1149-1154). PMID- 22777805 TI - Perineal reconstruction after abdominoperineal excision using inferior gluteal artery perforator flaps (Br J Surg 2012; 99: 584-588). PMID- 22777808 TI - Prognostic significance of peritoneal washing cytology in patients with gastric cancer (Br J Surg 2012; 99: 397-403). PMID- 22777811 TI - From nanographene and graphene nanoribbons to graphene sheets: chemical synthesis. AB - Graphene, an individual two-dimensional, atomically thick sheet of graphite composed of a hexagonal network of sp(2) carbon atoms, has been intensively investigated since its first isolation in 2004, which was based on repeated peeling of highly oriented pyrolyzed graphite (HOPG). The extraordinary electronic, thermal, and mechanical properties of graphene make it a promising candidate for practical applications in electronics, sensing, catalysis, energy storage, conversion, etc. Both the theoretical and experimental studies proved that the properties of graphene are mainly dependent on their geometric structures. Precise control over graphene synthesis is therefore crucial for probing their fundamental physical properties and introduction in promising applications. In this Minireview, we highlight the recent progress that has led to the successful chemical synthesis of graphene with a range of different sizes and chemical compositions based on both top-down and bottom-up strategies. PMID- 22777812 TI - Current percutaneous treatment strategies for saphenous vein graft disease. AB - Coronary artery bypass graft surgery remains one of the most widely performed surgical procedures in North America and aortocoronary saphenous vein grafts (SVG) are the most frequently used surgical conduits. SVG disease (SVGD) remains the leading cause of symptomatic coronary artery disease postcoronary artery bypass graft. When optimal medical therapy is ineffective, repeat surgery is associated with higher mortality combined with less favorable clinical and angiographic results, thus percutaneous revascularization on SVG is currently the standard of care for the revascularization of SVGD. Balloon angioplasty, bare metal stents, polytetrafluoroethylene-covered stents, and drug-eluting stents have been extensively investigated for SVG interventions. Multiple recent randomized trials and meta-analyses have confirmed the pathophysiologic and clinical differences between SVGD and coronary artery disease. Decisions such as patient selection, premedication, stent, and protection device characteristics should be carefully considered to achieve optimal procedural and clinical results. Acute coronary syndromes due to SVG involvement, chronic total occlusions, retrograde approaches, and SVG perforation management are newer fields requesting additional research. PMID- 22777813 TI - A novel application of plasmonics: plasmon-driven surface-catalyzed reactions. AB - The first experimental and theoretical evidence of the surface-catalyzed reaction of p,p'-dimercaptoazobenzene (DMAB) produced from para-aminothiophenol (PATP) by local surface plasmons was reported in 2010, and since that time a series of investigations have supported these findings using different experimental and theoretical methods. Recent work has also found that local plasmons can drive a surface-catalyzed reaction of DMAB converted from 4-nitrobenzenethiol (4NBT), assisted by local surface plasmons. There are at least three important discoveries in these investigations: 1) in the field of surface-enhanced Raman scattering (SERS) the widely accepted misinterpretation (since 1994) that the chemical mechanism resulting in three additional Raman peaks of PATP in Ag or Au solutions has been corrected with a new mechanism; 2) it is confirmed that SERS is not always a noninvasive technique, and under certain conditions cannot always obtain the vibrational fingerprint information of the original surface species; 3) a novel method to synthesize new molecules, induced by local surface plasmons or plasmon waveguides on the nanoscale, has been found. This Review considers recent novel applications of plasmonics to chemical reactions, especially to plasmon-driven surface-catalyzed reactions. PMID- 22777814 TI - Synthesis of geodesic polynuclear arenes and fullerenes by intramolecular aryl aryl coupling. AB - Bending over backwards to build buckybowls and -balls? For the last two decades, flash vacuum pyrolysis of chloro- and bromoarenes has been the method of choice for intramolecular aryl-aryl couplings that afford geodesic polynuclear arenes ("buckybowls") including fullerene C(60). Recently, even fluoroarenes were subjected under relatively mild conditions to intramolecular C(Ar)-C(Ar) couplings by combining the cleavage of C(Ar)-F with the formation of very strong Si-F or Al-F bonds (see picture; green C, white H). PMID- 22777815 TI - Cyclic tensile loading regulates human mesenchymal stem cell differentiation into neuron-like phenotype. AB - Mechanical loading has been utilized as an effective tool to direct mesenchymal stem cells (MSCs) commitment into cell lineages of mesodermal origin. However, the use of this tool to induce transdifferentiation of MSCs into the neural lineage has never been attempted. In this study, we examined the potential of uniaxial cyclic tensile loading in promoting neuronal differentiation of human MSCs (hMSCs) on modified biodegradable poly(epsilon-caprolactone) (PCL). The stem cell morphology, tissue-specific gene and protein expression, microfilament structure and, subsequently, Rho GTPase activity were analysed after cyclically stretching the cells at a range of amplitudes (0.5%, 2% or 3.5%) and frequencies (0.5, 1 or 1.5 Hz) for 8 h. hMSCs responded to these stimuli and displayed distinctly different microfilament organization. However, only those stretched at 0.5% strain amplitude and 0.5 Hz frequency showed promoted outgrowth of filopodia with significant upregulation of neurogenic genes expression. Positive staining of the neurogenic protein markers Nestin and Tuj1 suggested that the hMSCs had been committed to early neuronal progenitors. In addition, Rac1 but not RhoA was activated at this particular loading parameter. Furthermore, inhibition of Rac1 activity with NSC23766 disrupted the effect of cyclic loading. The results suggest that cyclic tensile loading at low amplitude and frequency is capable of triggering neuron-like differentiation through the regulation of Rho GTPases activity, even in the absence of neurogenic induction medium. PMID- 22777817 TI - Targeting of CD22-positive B-cell lymphoma cells by synthetic divalent sialic acid analogues. AB - CD22 is an inhibitory co-receptor of the B-cell receptor (BCR) on B cells. Since CD22 is ubiquitously expressed in the B-cell lineage and CD22 endocytosis can be triggered efficiently, antibodies and antibody-based immunotoxins against CD22 are used to target B cells both in B-cell lymphomas and leukemias, as well as in autoimmune diseases. CD22 recognizes alpha2,6-linked sialic acids as endogenous ligands. We have developed new synthetic sialosides as ligands for human CD22. These sialosides bind CD22 on human B cells with high affinity and can efficiently enhance IgM-triggered Ca(2+) signaling. We coupled these sialosides to Pseudomonas exotoxin A to generate a novel CD22 ligand-based immunotoxin. This sialoside-exotoxin-A construct can specifically kill CD22-positive B-cell lymphoma cells. It binds specifically to CD22-positive B-cell lymphoma cells and is dominant over endogenous cis-ligands on the B-cell surface. The sialoside exotoxin-A construct is efficiently internalized by endocytosis into B-cell lymphoma cell lines. Thus we show the development of a new therapeutic compound for targeting CD22 on human B cells, both for B-cell lymphoma, as well as for B cell-mediated autoimmune diseases. PMID- 22777818 TI - Toward the virtual cell: automated approaches to building models of subcellular organization "learned" from microscopy images. AB - We review state-of-the-art computational methods for constructing, from image data, generative statistical models of cellular and nuclear shapes and the arrangement of subcellular structures and proteins within them. These automated approaches allow consistent analysis of images of cells for the purposes of learning the range of possible phenotypes, discriminating between them, and informing further investigation. Such models can also provide realistic geometry and initial protein locations to simulations in order to better understand cellular and subcellular processes. To determine the structures of cellular components and how proteins and other molecules are distributed among them, the generative modeling approach described here can be coupled with high throughput imaging technology to infer and represent subcellular organization from data with few a priori assumptions. We also discuss potential improvements to these methods and future directions for research. PMID- 22777819 TI - Admittance tympanometry with 2-kHz probe tones in patients with low-frequency hearing loss. AB - OBJECTIVES/HYPOTHESIS: To assess the reliability of admittance tympanometry with 2-kHz probe tones in diagnosing ears with endolymphatic hydrops in patients with low-frequency hearing loss. STUDY DESIGN: Case-control study. METHODS: Thirty-six Japanese patients with low-frequency hearing loss (including 21 with Meniere disease, three with delayed endolymphatic hydrops, and 12 with acute or repetitious low-frequency sensorineural hearing loss), 18 patients with other types of hearing loss, and 16 subjects with normal hearing were enrolled at University of Tokyo Hospital. We measured the width of the splitting peaks in the admittance tymapnometry with 2-kHz probe tones. RESULTS: Widths of the probe pressure corresponding to splitting peaks of admittance (Y) tympanometry were significantly greater in the ears with endolymphatic hydrops than in the ears without endolymphatic hydrops in patients with low-frequency hearing loss. Furthermore, the widths in the ears with endolymphatic hydrops were greater than those in ears with other types of hearing loss. Widths of >255 daPa were observed in 38% of ears with endolymphatic hydrops and low-frequency hearing loss and in 21% of ears with other types of hearing loss. CONCLUSIONS: The current study demonstrated that wide splitting peaks of Y tympanometry are more frequently observed in ears showing low-frequency hearing loss than in those with other types of hearing loss, indicating that Y tympanometry can be used to diagnose endolymphatic hydrops in daily practice. PMID- 22777820 TI - Embodiment in social psychology. AB - Psychologists are increasingly interested in embodiment based on the assumption that thoughts, feelings, and behaviors are grounded in bodily interaction with the environment. We examine how embodiment is used in social psychology, and we explore the ways in which embodied approaches enrich traditional theories. Although research in this area is burgeoning, much of it has been more descriptive than explanatory. We provide a critical discussion of the trajectory of embodiment research in social psychology. We contend that future researchers should engage in a phenomenon-based approach, highlight the theoretical boundary conditions and mediators involved, explore novel action-relevant outcome measures, and address the role of individual differences broadly defined. Such research will likely provide a more explanatory account of the role of embodiment in general terms as well as how it expands the knowledge base in social psychology. PMID- 22777822 TI - Chemical interface damping in single gold nanorods and its near elimination by tip-specific functionalization. PMID- 22777821 TI - Analysis of protein function in clinical C. albicans isolates. AB - Clinical isolates are prototrophic and hence are not amenable to genetic manipulation using nutritional markers. Here we describe a new set of plasmids carrying the NAT1 (nourseothricin) drug resistance marker (Shen et al., ), which can be used both in clinical isolates and in laboratory strains. We constructed novel plasmids containing HA-NAT1 or MYC-NAT1 cassettes to facilitate PCR mediated construction of strains with C-terminal epitope-tagged proteins and a NAT1-pMet3-GFP plasmid to enable conditional expression of proteins with or without the green fluorescent protein fused at the N-terminus. Furthermore, for proteins that require both the endogenous N- and C-termini for function, we have constructed a GF-NAT1-FP cassette carrying truncated alleles that facilitate insertion of an intact, single copy of GFP internal to the coding sequence. In addition, GFP-NAT1, RFP-NAT1 and M-Cherry-NAT1 plasmids were constructed, expressing two differently labelled gene products for the study of protein co expression and co-localization in vivo. Together, these vectors provide a useful set of genetic tools for studying diverse aspects of gene function in both clinical and laboratory strains of C. albicans. PMID- 22777823 TI - Baseline tumor oxygen saturation correlates with a pathologic complete response in breast cancer patients undergoing neoadjuvant chemotherapy. AB - Tissue hemoglobin oxygen saturation (i.e., oxygenation) is a functional imaging endpoint that can reveal variations in tissue hypoxia, which may be predictive of pathologic response in subjects undergoing neoadjuvant chemotherapy. In this study, we used diffuse optical spectroscopic imaging (DOSI) to measure concentrations of oxyhemoglobin (ctO(2)Hb), deoxy-hemoglobin (ctHHb), total Hb (ctTHb = ctO(2)Hb + ctHHb), and oxygen saturation (stO(2) = ctO(2)Hb/ctTHb) in tumor and contralateral normal tissue from 41 patients with locally advanced primary breast cancer. Measurements were acquired before the start of neoadjuvant chemotherapy. Optically derived parameters were analyzed separately and in combination with clinical biomarkers to evaluate correlations with pathologic response. Discriminant analysis was conducted to determine the ability of optical and clinical biomarkers to classify subjects into response groups. Twelve (28.6%) of 42 tumors achieved pathologic complete response (pCR) and 30 (71.4%) were non pCR. Tumor measurements in pCR subjects had higher stO(2) levels (median 77.8%) than those in non-pCR individuals (median 72.3%, P = 0.01). There were no significant differences in baseline ctO(2)Hb, ctHHb, and ctTHb between response groups. An optimal tumor oxygenation threshold of stO(2) = 76.7% was determined for pCR versus non-pCR (sensitivity = 75.0%, specificity = 73.3%). Multivariate discriminant analysis combining estrogen receptor staining and stO(2) further improved the classification of pCR versus non-pCR (sensitivity = 100%, specificity = 85.7%). These results show that elevated baseline tumor stO(2) are correlated with a pCR. Noninvasive DOSI scans combined with histopathology subtyping may aid in stratification of individual patients with breast cancer before neoadjuvant chemotherapy. PMID- 22777824 TI - Global quantitative phosphoproteome analysis of human tumor xenografts treated with a CD44 antagonist. AB - The cell surface glycoprotein CD44 plays an important role in the development and progression of various tumor types. RG7356 is a humanized antibody targeting the constant region of CD44 that shows antitumor efficacy in mice implanted with CD44 expressing tumors such as MDA-MB-231 breast cancer cells. CD44 receptor seems to function as the main receptor for hyaluronic acid and osteopontin, serving as coreceptor for growth factor pathways like cMet, EGFR, HER-2, and VEGFR and by cytoskeletal modulation via ERM and Rho kinase signaling. To assess the direct impact of RG7356 binding to the CD44 receptor, a global mass spectrometry-based phosphoproteomics approach was applied to freshly isolated MDA-MB-231 tumor xenografts. Results from a global phosphoproteomics screen were further corroborated by Western blot and ELISA analyses of tumor lysates from CD44 expressing tumors. Short-term treatment of tumor-bearing mice with RG7356 resulted in modifications of the MAPK pathway in the responsive model, although no effects on downstream phosphorylation were observed in a nonresponsive xenograft model. Taken together, our approach augments the value of other high throughput techniques to identify biomarkers for clinical development of targeted agents. PMID- 22777825 TI - High-dose plasmid-mediated VEGF gene transfer is safe in patients with severe ischemic heart disease (Genesis-I). A phase I, open-label, two-year follow-up trial. AB - OBJECTIVES: We aimed to assess safety and, secondarily, the efficacy of intramyocardial high-dose plasmid-vascular endothelial growth factor (VEGF) 165 (pVEGF165) gene transfer in no-option patients with coronary artery disease (CAD). BACKGROUND: Controlled trials of pVEGF165 in CAD have shown little benefit. One possible reason is shortness of dosage. We have shown in large mammalian models of chronic myocardial ischemia and acute myocardial infarction that intramyocardial pVEGF165 at doses significantly higher than those used in recent phase II trials is safe and efficacious on myocardial perfusion, left ventricular function, and infarct size limitation. METHODS: Using an injection catheter, 10 patients with severe CAD not amenable for revascularization received 10 intramyocardial injections of 0.38 mg (total dose, 3.8 mg) pVEGF165 in zones exhibiting myocardial ischemia, as assessed by combined stress 99mTc-sestamibi single-photon emission computed tomography and stress echocardiography. RESULTS: No serious adverse events related to either VEGF or the injection procedure occurred over the 2-year follow-up. One patient suffered femoral artery thrombosis after a follow-up coronary angiography, successfully resolved with medical treatment. Six patients suffered uncomplicated coronary ischemic events during the second year follow-up. Angina functional class decreased from 2.6 +/- 0.2 to 1.2 +/- 0.3 (mean +/- SEM, P < 0.05), quality of life increased from 56.9 +/- 3.2 to 82.6 +/- 2.4 (P < 0.05), the summed difference score of myocardial perfusion decreased from 13.4 +/- 2 to 7.7 +/- 1.8 (P < 0.04), and stress ejection fraction did not change (44.2 +/- 3.6% to 47.8 +/- 3.1%, P = NS). CONCLUSIONS: High-dose intramyocardial pVEGF165 is safe at 2 years follow-up in patients with severe CAD. The efficacy results observed must be taken cautiously given the uncontrolled, open-label study design. PMID- 22777826 TI - Functions and action mechanisms of flavonoids genistein and icariin in regulating bone remodeling. AB - Increasingly natural products particularly flavonoids are being explored for their therapeutic potentials in reducing bone loss and maintaining bone health. This study has reviewed previous studies on the two better known flavonoids, genistein and icariin, their structures, functions, action mechanisms, relative potency, and potential application in regulating bone remodeling and preventing bone loss. Genistein, an isoflavone abundant in soy, has dual functions on bone cells, able to inhibit bone resorption activity of osteoclasts and stimulate osteogenic differentiation and maturation of bone marrow stromal progenitor cells (BMSCs) and osteoblasts. Genistein is an estrogen receptor (ER)-selective binding phytoestrogen, with a greater affinity to ERbeta. Genistein inhibits tyrosine kinases and inhibits DNA topoisomerases I and II, and may act as an antioxidant. Genistein enhances osteoblastic differentiation and maturation by activation of ER, p38MAPK-Runx2, and NO/cGMP pathways, and it inhibits osteoclast formation and bone resorption through inducing osteoclastogenic inhibitor osteoprotegerin (OPG) and blocking NF-kappaB signaling. Icariin, a prenylated flavonol glycoside isolated from Epimedium herb, stimulates osteogenic differentiation of BMSCs and inhibits bone resorption activity of osteoclasts. Icariin, whose metabolites include icariside I, icariside II, icaritin, and desmethylicaritin, has no estrogenic activity. However, icariin is more potent than genistein in promoting osteogenic differentiation and maturation of osteoblasts. The existence of a prenyl group on C-8 of icariin molecular structure has been suggested to be the reason why icariin is more potent than genistein in osteogenic activity. Thus, the prenylflavonoids may represent a class of flavonoids with a higher osteogenic activity. PMID- 22777827 TI - Different concentrations of grape seed extract affect in vitro starch fermentation by porcine small and large intestinal inocula. AB - BACKGROUND: Grape seed extract (GSE) phenolics have potential health-promoting properties, either from compounds present within the extract, or metabolites resulting from gastrointestinal tract (GIT) fermentation of these compounds. This study describes how GSE affected the kinetics and end-products of starch fermentation in vitro using pig intestinal and fecal inocula. Six GSE concentrations (0, 60, 125, 250, 500, and 750 ug ml-1 were fermented in vitro by porcine ileal and fecal microbiota using starch as the energy source. Cumulative gas production, and end-point short chain fatty acids and ammonia were measured. RESULTS: GSE phenolics altered the pattern (gas kinetics, and end-products such as SCFA and NH4+) of starch fermentation by both inocula, at concentrations above 250 ug ml-1 . Below this level, neither inoculum showed any significant (P > 0.05) effect of the GSE. CONCLUSION: The results show that GSE phenolics at a concentration over 250 ug ml-1 can have measurable effects on microbial activity in an in vitro fermentation system, as evidenced by the changes in kinetics and end-products from starch fermentation. This suggests that fermentation patterns could be conceivably shifted in the actual GIT, though further evidence will be required from in vivo studies. PMID- 22777828 TI - Photochemical synthesis of a ladder diborole: a new boron-containing conjugate material. AB - Climbing the ladder: Reductive cyclization of alkynyl haloboranes lead to the bis benzocycloborabutylidene rather than the expected ladder diborole, despite the former being much less thermodynamically favored. Photochemical conversion to the ladder diborole was, however, quite facile upon irradiation at 254 nm. PMID- 22777829 TI - Characterization of dopamine D1 and D2 receptor-expressing neurons in the mouse hippocampus. AB - The hippocampal formation is part of an anatomical system critically involved in learning and memory. Increasing evidence suggests that dopamine plays an important role in learning and memory as well as in several forms of synaptic plasticity. However, the precise identification of neuronal populations expressing D1 or D2 dopamine receptors within the hippocampus is still lacking. To clarify this issue, we used BAC transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoter of dopamine D1 or D2 receptors. In Drd1a-EGFP mice, sparse GFP-expressing neurons were detected among glutamatergic projecting neurons of the granular layer of the dentate gyrus and GABAergic interneurons located in the hilus. A dense immunofluorescence was observed in the outer and medial part of the molecular layer of the dentate gyrus as well as in the inner part of the molecular layer of CA1 corresponding to the terminals of pyramidal neurons of the entorhinal cortex defining the perforant and the temporo-ammonic pathway respectively. Finally, scattered D1 receptor expressing neurons were also identified as GABAergic interneurons in the CA3/CA1 fields of the hippocampus. In Drd2-EGFP transgenic mice, GFP was exclusively detected in the glutamatergic mossy cells located in the polymorphic layer of the dentate gyrus. This pattern was confirmed in Drd2-Cre mice crossed with NLS-LacZ Tau(mGFP) :LoxP and RCE:LoxP reporter lines. Our results demonstrate that D1 and D2 receptor-expressing neurons are strictly segregated in the mouse hippocampus. By clarifying the identity of D1 and D2 receptor-expressing neurons in the hippocampus, this study establishes a basis for future investigations aiming at elucidating their roles in the hippocampal network. PMID- 22777830 TI - The catalytic domain of the germination-specific lytic transglycosylase SleB from Bacillus anthracis displays a unique active site topology. AB - Bacillus anthracis produces metabolically inactive spores. Germination of these spores requires germination-specific lytic enzymes (GSLEs) that degrade the unique cortex peptidoglycan to permit resumption of metabolic activity and outgrowth. We report the first crystal structure of the catalytic domain of a GSLE, SleB. The structure revealed a transglycosylase fold with unique active site topology and permitted identification of the catalytic glutamate residue. Moreover, the structure provided insights into the molecular basis for the specificity of the enzyme for muramic-delta-lactam-containing cortex peptidoglycan. The protein also contains a metal-binding site that is positioned directly at the entrance of the substrate-binding cleft. PMID- 22777831 TI - Superparamagnetic iron oxide nanoparticles (SPION) for the treatment of antibiotic-resistant biofilms. AB - Bacterial infections caused by antibiotic-resistant strains are of deep concern due to an increasing prevalence, and are a major cause of morbidity in the United States of America. In particular, medical device failures, and thus human lives, are greatly impacted by infections, where the treatments required are further complicated by the tendency of pathogenic bacteria, such as Staphylococcus aureus, to produce antibiotic resistant biofilms. In this study, a panel of relevant antibiotics used clinically including penicillin, oxacillin, gentamicin, streptomycin, and vancomycin are tested, and although antibiotics are effective against free-floating planktonic S. aureus, either no change in biofilm function is observed, or, more frequently, biofilm function is enhanced. As an alternative, superparamagnetic iron oxide nanoparticles (SPION) are synthesized through a two-step process with dimercaptosuccinic acid as a chelator, followed by the conjugation of metals including iron, zinc, and silver; thus, the antibacterial properties of the metals are coupled to the superparamagnetic properties of SPION. SPION might be the ideal antibacterial treatment, with a superior ability to decrease multiple bacterial functions, target infections in a magnetic field, and had activity better than antibiotics or metal salts alone, as is required for the treatment of medical device infections for which no treatment exists today. PMID- 22777833 TI - Construction of tissue-engineered osteochondral composites and repair of large joint defects in rabbit. AB - In this study, a novel three-dimensional (3D) heterogeneous/bilayered scaffold was constructed to repair large defects in rabbit joints. The scaffold includes two distinct but integrated layers corresponding to the cartilage and bone components. The upper layer consists of gelatin, chondroitin sulphate and sodium hyaluronate (GCH), and the lower layer consists of gelatin and ceramic bovine bone (GCBB). The two form a 3D bilayered scaffold (GCH-GCBB), which mimics the natural osteochondral matrix for use as a scaffold for osteochondral tissue engineering. The purpose of this study was to evaluate the efficacy of this novel scaffold, combined with chondrocytes and bone marrow stem cells (BMSCs) to repair large defects in rabbit joints. Thirty-six large defects in rabbit femoral condyles were created; 12 defects were treated with the same scaffold combined with cells (group A); another 12 defects were treated with cell-free scaffolds (group B); the others were untreated (group C). At 6 and 12 weeks, in group A hyaline-like cartilage formation could be observed by histological examination; the newly formed cartilage, which stained for type II collagen, was detected by RT-PCR at high-level expression. Most of the GCBB was replaced by bone, while little remained in the underlying cartilage. At 36 weeks, GCBB was completely resorbed and a tidemark was observed in some areas. In contrast, groups B and C showed no cartilage formation but a great amount of fibrous tissue, with only a little bone formation. In summary, this study demonstrated that a novel scaffold, comprising a top layer of GCH, having mechanical properties comparable to native cartilage, and a bottom layer composed of GCBB, could be used to repair large osteochondral defects in joints. PMID- 22777832 TI - The role of qualitative and quantitative analysis of F18-FDG positron emission tomography in predicting pathologic response following chemoradiotherapy in patients with esophageal carcinoma. AB - OBJECTIVE: The aim of this study was to determine if a qualitative and quantitative assessment of pre- and post-chemoradiotherapy (CRT) F18-FDG PET scans of esophageal cancer patients could predict for residual disease in esophagectomy specimens. METHODS: We retrospectively reviewed the records of esophageal cancer patients who had undergone CRT at a single institution. Analysis was limited to esophagectomy patients with both pre- and post-CRT F18 FDG PET scans. The maximum standardized uptake value (SUV), location, and measured length of esophagus with increased F18-FDG uptake were obtained from the PET scan before and 3-4 weeks following CRT (preoperatively). The pattern of F18 FDG uptake was qualitatively assigned a category of diffuse, focal, or diffuse with focal component. RESULTS: Fifty-seven patients with localized esophageal carcinoma underwent F18-FDG PET/CT scans as part of their initial staging and post-CRT restaging workup, followed by esophagectomy. The pathologic complete response (pCR) rate was 25%. The presence of a focal component on post-CRT PET predicted residual disease on univariate analysis (86% vs. 64%), and achieved significance when controlling for SUV and presence of diabetes on MVA (OR = 5.59, p = 0.028). There was no significant relationship between pre- or post-CRT SUV, tumor histology, or length of increased F18-FDG uptake and presence of residual disease. SUV and focality did not interact significantly to predict residual disease. CONCLUSIONS: Qualitative but not quantitative PET imaging can help predict increased likelihood of residual tumor in esophageal cancer patients following CRT; however, it is not sensitive enough to solely rule out the presence of residual disease. Additional investigation with a larger cohort of patients is warranted. PMID- 22777835 TI - Abstracts of the Association of Surgeons from the Netherlands (ASN) Spring Meeting (Chirurgendagen). May 10-11, 2012. Veldhoven, the Netherlands. PMID- 22777834 TI - Response of HT29 colorectal xenograft model to cediranib assessed with 18 F fluoromisonidazole positron emission tomography, dynamic contrast-enhanced and diffusion-weighted MRI. AB - Cediranib is a small-molecule pan-vascular endothelial growth factor receptor inhibitor. The tumor response to short-term cediranib treatment was studied using dynamic contrast-enhanced and diffusion-weighted MRI at 7 T, as well as (18) F fluoromisonidazole positron emission tomography and histological markers. Rats bearing subcutaneous HT29 human colorectal tumors were imaged at baseline; they then received three doses of cediranib (3 mg/kg per dose daily) or vehicle (dosed daily), with follow-up imaging performed 2 h after the final cediranib or vehicle dose. Tumors were excised and evaluated for the perfusion marker Hoechst 33342, the endothelial cell marker CD31, smooth muscle actin, intercapillary distance and tumor necrosis. Dynamic contrast-enhanced MRI-derived parameters decreased significantly in cediranib-treated tumors relative to pretreatment values [the muscle-normalized initial area under the gadolinium concentration curve decreased by 48% (p=0.002), the enhancing fraction by 43% (p=0.003) and K(trans) by 57% (p=0.003)], but remained unchanged in controls. No change between the pre- and post-treatment tumor apparent diffusion coefficients in either the cediranib- or vehicle-treated group was observed over the course of this study. The (18) F fluoromisonidazole mean standardized uptake value decreased by 33% (p=0.008) in the cediranib group, but showed no significant change in the control group. Histological analysis showed that the number of CD31-positive vessels (59 per mm(2) ), the fraction of smooth muscle actin-positive vessels (80-87%) and the intercapillary distance (0.17 mm) were similar in cediranib- and vehicle-treated groups. The fraction of perfused blood vessels in cediranib-treated tumors (81 +/ 7%) was lower than that in vehicle controls (91 +/- 3%, p=0.02). The necrotic fraction was slightly higher in cediranib-treated rats (34 +/- 12%) than in controls (26 +/- 10%, p=0.23). These findings suggest that short-term treatment with cediranib causes a decrease in tumor perfusion/permeability across the tumor cross-section, but changes in vascular morphology, vessel density or tumor cellularity are not manifested at this early time point. PMID- 22777836 TI - Modeling HIV infection and therapies in humanized mice. AB - The human immunodeficiency virus (HIV) type-1 is a human-specific virus. The lack of a widely available small-animal model has seriously hampered HIV research. In 2004, a new humanised mouse model was reported. It was based on the intrahepatic injection of human CD34+ cord blood cells into newborn, highly immunodeficient mice. These mice develop a lymphoid system of human origin and are highly susceptible to HIV infection and showed disseminated infection, persistent viraemia and characteristic helper CD4+ T-cell loss. Here, we will briefly review the various existing humanised mouse models and highlight their value to the study of HIV infection. PMID- 22777838 TI - Usage of four-phase high-resolution rhinomanometry and measurement of nasal resistance in sleep-disordered breathing. AB - OBJECTIVES/HYPOTHESIS: To investigate the ease of use of four-phase high resolution rhinomanometry (HRR), a new way of measuring nasal resistance, in measuring change in nasal resistance from supine to inclined position in a clinical sleep laboratory setting, and to correlate findings with continuous positive airway pressure (CPAP) tolerance. STUDY DESIGN: Retrospective review of clinical charts. METHODS: Forty successively seen Caucasian subjects diagnosed with sleep-disordered breathing (SDB) with complete charts were analyzed. Using four-phase HRR and acoustic rhinometry, nasal resistance and minimal cross sectional area of the nasal cavity were objectively measured with the patient in the supine position and repeated in the inclined position (30 degrees from the horizontal plane), respectively. RESULTS: From the supine to inclined position, reduction in total nasal resistance was observed in 87.5% (35 out of 40). There was a mean reduction of nasal resistance by 37.1 +/- 21.6%. Five (12.5%) out of 40 subjects showed no change or mild increase in nasal resistance. Subjects with nasal resistance unresponsive to the inclined position change tended to have difficulty using nasal CPAP based on downloaded compliance card data. CONCLUSIONS: Four-phase HRR and acoustic rhinometry are tests that can be easily performed by sleep specialists to characterize nasal resistance in SDB patients and determine changes in resistance with positional changes. In this study, we found that patients who did not demonstrate a decrease in nasal resistance with inclined position were more likely to be noncompliant with nasal CPAP. These measurements may help us objectively identify patients who might have trouble tolerating nasal CPAP. PMID- 22777837 TI - The genome in space and time: does form always follow function? How does the spatial and temporal organization of a eukaryotic genome reflect and influence its functions? AB - Recent systematic studies using newly developed genomic approaches have revealed common mechanisms and principles that underpin the spatial organization of eukaryotic genomes and allow them to respond and adapt to diverse functional demands. Genomes harbor, interpret, and propagate genetic and epigenetic information, and the three-dimensional (3D) organization of genomes in the nucleus should be intrinsically linked to their biological functions. However, our understanding of the mechanisms underlying both the topological organization of genomes and the various nuclear processes is still largely incomplete. In this essay, we focus on the functional relevance as well as the biophysical properties of common organizational themes in genomes (e.g. looping, clustering, compartmentalization, and dynamics), and examine the interconnection between genome structure and function from this angle. Present evidence supports the idea that, in general, genome architecture reflects and influences genome function, and is relatively stable. However, the answer as to whether genome architecture is a hallmark of cell identity remains elusive. PMID- 22777839 TI - Why differentiating between health system support and health system strengthening is needed. AB - There is increasing recognition that efforts to improve global health cannot be achieved without stronger health systems. Interpretation of health system strengthening (HSS) has varied widely however, with much of the focus to-date on alleviating input constraints, whereas less attention has been given to other performance drivers. It is important to distinguish activities that support the health system, from ones that strengthen the health system. Supporting the health system can include any activity that improves services, from distributing mosquito nets to procuring medicines. These activities improve outcomes primarily by increasing inputs. Strengthening the health system is accomplished by more comprehensive changes to performance drivers such as policies and regulations, organizational structures, and relationships across the health system to motivate changes in behavior and/or allow more effective use of resources to improve multiple health services. Even organizations that have made significant investments in health systems have not provided guidance on what HSS entails. While both supporting and strengthening are important and necessary, it is nonetheless important to make a distinction. If activities fail to produce improvements in system performance because they were incorrectly labeled as system strengthening, the value of HSS investments could quickly be discredited. Not distinguishing supportive activities from strengthening ones will lead to unmet expectations of stronger health systems, as well as neglect of critical system strengthening activities. Distinguishing between these two types of activities will improve programming impact. PMID- 22777840 TI - The human mitochondrial transcriptome and the RNA-binding proteins that regulate its expression. AB - The human mitochondrial transcriptome, although produced from a small and compact genome, has revealed surprising complexity in its composition and regulation. Wide variation between individual tRNAs, mRNAs, and rRNAs indicate the importance of post-transcriptional processing, maturation, and degradation mechanisms in the regulation of mitochondrial gene expression. RNA-binding proteins play essential roles in controlling the mitochondrial transcriptome from its synthesis to its destruction and have evolved unique features to complement the unusual features of mitochondrial RNAs. Recent studies have shown how changes in mitochondrial RNAs and their binding proteins can have significant effects on human health. This opens new avenues for investigation of mitochondrial RNA-binding proteins and the mechanisms by which they regulate mitochondrial gene expression. PMID- 22777842 TI - Does chemistry have a future in therapeutic innovations? PMID- 22777841 TI - Formation of soy protein isolate-dextran conjugates by moderate Maillard reaction in macromolecular crowding conditions. AB - BACKGROUND: Several methods have been reported for the conjugation of proteins with polysaccharides. Protein-polysaccharide conjugates can be formed by traditional dry heating, but this process is not attractive from an industrial viewpoint, and no commercial conjugates have been manufactured in this way. In the present study, in order to develop a more practical reaction method, macromolecular crowding was used to attach polysaccharides to proteins. RESULTS: Soy protein isolate-dextran conjugates (SDCs) were prepared via the initial stage of the Maillard reaction in macromolecular crowding conditions. The impact of various processing conditions on the formation of SDCs was investigated. The optimal conditions chosen from the experiments were a soy protein isolate/dextran ratio of 1:1 (w/w), a pH of 6.5, a reaction temperature of 60 degrees C and a reaction time of 30 h. Circular dichroism spectroscopy showed that the secondary and tertiary structures of the conjugates were changed significantly. Structural flexibility increased, allowing better display of their functional characteristics. The conjugates had a composition with various sizes, especially macromolecules, according to gel permeation chromatography. Thermal analysis showed that the thermal stability of the conjugates was improved. CONCLUSION: The production of SDCs under macromolecular crowding conditions appears to be an effective and promising technique, representing an advance over classic protein glycosylation methods. PMID- 22777843 TI - Recognition of fungal RNA by TLR7 has a nonredundant role in host defense against experimental candidiasis. AB - Despite convincing evidence for involvement of members of the Toll-like receptor (TLR) family in fungal recognition, little is known of the functional role of individual TLRs in antifungal defenses. We found here that TLR7 was partially required for the induction of IL-12 (IL-12p70) by Candida albicans or Saccharomyces cerevisiae. Moreover, the IL-12p70 response was completely abrogated in cells from 3d mice, which are unable to mobilize TLRs to endosomal compartments, as well as in cells from mice lacking either the TLR adaptor MyD88 or the IRF1 transcription factor. Notably, purified fungal RNA recapitulated IL 12p70 induction by whole yeast. Although RNA could also induce moderate TLR7 dependent IL-23 and tumor necrosis factor-alpha (TNF-alpha) secretion, TLR7 and other endosomal TLRs were redundant for IL-23 or TNF-alpha induction by whole fungi. Importantly, mice lacking TLR7 or IRF1 were hypersusceptible to systemic C. albicans infection. Our data suggest that IRF1 is downstream of a novel, nonredundant fungal recognition pathway that has RNA as a major target and requires phagosomal recruitment of intracellular TLRs. This pathway differs from those involved in IL-23 or TNF-alpha responses, which we show here to be independent from translocation of intracellular TLRs, phagocytosis, or phagosomal acidification. PMID- 22777844 TI - Recurrent dyspnea following multiple ablations for atrial fibrillation explained by the "stiff left atrial syndrome". AB - We present the case of a patient who underwent repeated ablations for atrial fibrillation and presented with recurrent dyspnea, elevated left atrial pressure with large V waves in the absence of mitral regurgitation. This case provides an example of "stiff left atrial syndrome" as has been described in patients with mitral valve replacement and only recently in patients with radiofrequency ablations for atrial fibrillation. PMID- 22777845 TI - Multi-phase extraction of glycoraphanin from broccoli using aminium ionic liquid based silica. AB - INTRODUCTION: Glucosinolates, a class of phytochemicals found in broccoli, have attracted recent interest due to the potential health benefits associated with their dietary intake. Glucoraphanin, the most common glucosinolate in broccoli can be converted to a known cancer chemopreventive agent. Multi-phase extraction in solid-phase extraction cartridges was developed to simultaneously extract and separate this compound. OBJECTIVE: Multi-phase extraction with functionalised ionic liquid-based silica as a sorbent was used to simultaneously extract and separate glucoraphanin from broccoli. METHODOLOGY: The sorbent and broccoli sample were packed into a single cartridge, and a fixed volume of water was then used to extract and remove the target compound from the sample to the sorbent over 15 repetitions. The sorbent was then washed with n-hexane to remove any interference and the target compound was eluted with water-1% acetic acid (vol.). RESULTS: Under the optimised condition, 0.038 mg/g of glucoraphanin was obtained by multi-phase extraction with 0.2 g of sorbent. CONCLUSION: The adsorption isotherm allowed investigation of the interactions between the sorbent and target compound and provided evidence for the accuracy of this method. The low deviation error, small amount of solvents required, highly selective separation and stability of the method justify further research. PMID- 22777846 TI - Substrate templating upon self-assembly of hydrogen-bonded molecular networks on an insulating surface. AB - Molecular self-assembly on insulating surfaces, despite being highly relvant to many applications, generally suffers from the weak molecule-surface interactions present on dielectric surfaces, especially when benchmarked against metallic substrates. Therefore, to fully exploit the potential of molecular self-assembly, increasing the influence of the substrate constitutes an essential prerequisite. Upon deposition of terephthalic acid and trimesic acid onto the natural cleavage plane of calcite, extended hydrogen-bonded networks are formed, which wet the substrate. The observed structural complexity matches the variety realized on metal surfaces. A detailed analysis of the molecular structures observed on calcite reveals a significant influence of the underlying substrate, clearly indicating a substantial templating effect of the surface on the resulting molecular networks. This work demonstrates that choosing suitable molecule/substrate systems allows for tuning the balance between intermolecular and molecule-surface interactions even in the case of typically weakly interacting insulating surfaces. This study, thus, provides a strategy for deliberately exploiting substrate templating to increase the structural variety in molecular self-assembly on a bulk insulator at room temperature. PMID- 22777848 TI - HapMap European American genotypes are compatible with the hypothesis of MHC dependent mate choice (response to DOI 10.1002/bies.201200023, Derti and Roth). PMID- 22777847 TI - Proton density fat-fraction: a standardized MR-based biomarker of tissue fat concentration. PMID- 22777849 TI - Delayed rupture of the extensor digitorum tendon of the index finger after a distal radial fracture in a child. PMID- 22777850 TI - How placement affects force and contact pressure between a volar plate of the distal radius and the flexor pollicus longus tendon: a biomechanical investigation. AB - Open reduction and internal fixation of a distal radius fracture can leave a volar plate in close proximity or touching the tendons of the wrist. This cadaveric study examines the how volar plate position changes contact pressure and force against the flexor pollicis longus (FPL) tendon in multiple wrist extension positions. This study suggests that moving the plate from an ideal position (distal edge at the watershed line) to a malposition (5 mm distal to the watershed line) significantly increased the force by 72.7% and contact pressure by 33.5% on the FPL. Multiple clinical case reports have described rupture of the flexor tendons associated with distally positioned plates or protruding screw heads, creating prominent or sharp edges. This study illustrates that in order to minimize contact pressure on the flexor tendons, plating distal to the watershed line should be avoided when possible. PMID- 22777851 TI - Bone resorption of the proximal phalanx secondary to pulley reconstruction. PMID- 22777852 TI - Metacarpophalangeal joint arthroscopy: outcomes for the painful, radiographically normal joint. PMID- 22777853 TI - Rebalancing the tetraplegic wrist using extensor carpi ulnaris-tenodesis. AB - Patients with cervical spinal cord injury and tetraplegia often present with a radial deviation deformity of the wrist owing to impaired active wrist flexion and extension. Tenodesis of the extensor carpi ulnaris can help optimize grip strength. The purpose of the study was to compare reconstruction of the grip with and without extensor carpi ulnaris-tenodesis, as well as evaluating the outcome of the procedure. The grip strength of the group with tenodesis of the extensor carpi ulnaris was twice as strong as of the group without the tenodesis and with similar wrist joint flexion-extension range of motion. Correction of the wrist deformity enables a more ergonomic use of the hand. This may also help prevent shoulder pain, which is common among patients with tetraplegia. PMID- 22777854 TI - Electrostatic interactions play an essential role in the binding of oleic acid with alpha-lactalbumin in the HAMLET-like complex: a study using charge-specific chemical modifications. AB - Human alpha-lactalbumin made lethal to tumor cells (HAMLET) and its analogs are partially unfolded protein-oleic acid (OA) complexes that exhibit selective tumoricidal activity normally absent in the native protein itself. To understand the nature of the interaction between protein and OA moieties, charge-specific chemical modifications of lysine side chains involving citraconylation, acetylation, and guanidination were employed and the biophysical and biological properties were probed. Upon converting the original positively-charged lysine residues to negatively-charged citraconyl or neutral acetyl groups, the binding of OA to protein was eliminated, as were any cytotoxic activities towards osteosarcoma cells. Retention of the positive charges by converting lysine residues to homoarginine groups (guanidination); however, yielded unchanged binding of OA to protein and identical tumoricidal activity to that displayed by the wild-type alpha-lactalbumin-oleic acid complex. With the addition of OA, the wild-type and guanidinated alpha-lactalbumin proteins underwent substantial conformational changes, such as partial unfolding, loss of tertiary structure, but retention of secondary structure. In contrast, no significant conformational changes were observed in the citraconylated and acetylated alpha-lactalbumins, most likely because of the absence of OA binding. These results suggest that electrostatic interactions between the positively-charged basic groups on alpha lactalbumin and the negatively-charged carboxylate groups on OA molecules play an essential role in the binding of OA to alpha-lactalbumin and that these interactions appear to be as important as hydrophobic interactions. PMID- 22777856 TI - Evidence-based decisions for local and systemic wound care. AB - BACKGROUND: Decisions on local and systemic wound treatment vary among surgeons and are frequently based on expert opinion. The aim of this meta-review was to compile best available evidence from systematic reviews in order to formulate conclusions to support evidence-based decisions in clinical practice. METHODS: All Cochrane systematic reviews (CSRs), published by the Cochrane Wounds and Peripheral Vascular Diseases Groups, and that investigated therapeutic and preventive interventions, were searched in the Cochrane Database up to June 2011. Two investigators independently categorized each intervention into five levels of evidence of effect, based on size and homogeneity, and the effect size of the outcomes. RESULTS: After screening 149 CSRs, 44 relevant reviews were included. These contained 109 evidence-based conclusions: 30 on venous ulcers, 30 on acute wounds, 15 on pressure ulcers, 14 on diabetic ulcers, 12 on arterial ulcers and eight on miscellaneous chronic wounds. Strong conclusions could be drawn regarding the effectiveness of: therapeutic ultrasonography, mattresses, cleansing methods, closure of surgical wounds, honey, antibiotic prophylaxis, compression, lidocaine-prilocaine cream, skin grafting, antiseptics, pentoxifylline, debridement, hyperbaric oxygen therapy, granulocyte colony stimulating factors, prostanoids and spinal cord stimulation. CONCLUSION: For some wound care interventions, robust evidence exists upon which clinical decisions should be based. PMID- 22777857 TI - Correlation between neuropsychological tests and hypoperfusion in MCI patients: anatomical labeling using xjView and Talairach Daemon software. AB - PURPOSE: Statistical analysis of brain perfusion SPECT images has shown mild to severe abnormalities, consistent with cortical dysfunctions in the brain. Recently, functional brain imaging such as fMRI, PET and SPECT is increasingly used for diagnosis of MCI. In this study, we calculate the correlation with perfusion of brain SPECT and neuropsychological test scores of patients by SPM analysis to evaluate the relationship with cerebral hypoperfusion and cognitive dysfunction in MCI patients. Anatomical labeling was performed automatically using the Talairach Daemon (TD) and xjView. METHODS: Ninety-three patients (mean age 67.2 +/- 7.42 years; 59 women and 34 men) with MCI were selected and examined by the comprehensive neuropsychological test. Tc-99m-HMPAO brain SPECT images were acquired on the patients using a two-head gamma camera. We analyzed the brain image of MCI patients by SPM8 software, and observed the anatomical correlated region, between the neuropsychological tests and cerebral hypoperfusion. The SPM8 tool provided correlation between neuropsychological score and brain perfusion by simple regression method. The neuropsychological test included attention, language function, visuospatial function, memory, frontal executive function, depression score and general cognitive function. RESULTS: Percentage of voxels with correlated area to the whole brain was calculated and the values by Rey complex figure test (CFT) copy score, MMSE score, Seoul verbal learning test (SVLT) immediate recall score and Rey CFT delayed recall score were 15.3, 12.33, 10.59 and 8.45 %, respectively. Rey CFT copy score was correlated with perfusion in the left middle temporal gyrus (BA 21), right inferior frontal gyrus (BA 45), right lingual gyrus, left lingual gyrus (BA 18), right postcentral gyrus (BA 40), right cingulate gyrus (BA 31) and left thalamus (pulvinar) with p < 0.01 FDR. The correlation related to MMSE included left parahippocampal gyrus, right fusiform gyrus and right middle frontal gyrus (BA 46). SVLT immediate recall score was correlated with left superior temporal gyrus and Rey CFT delayed recall score was correlated with left inferior frontal gyrus (BA 47), right inferior frontal gyrus, and left lentiform nucleus. Visuospatial and general cognitive dysfunctions in the patients with MCI were most correlated with cerebral hypoperfusion. CONCLUSIONS: Rey CFT copy and MMSE scores were more strongly correlated with blood perfusion of the brain than with other neuropsychological test scores. xjView was a useful tool to find out the anatomical name of the selected voxel or clusters and to display the cluster's anatomical information and list all cluster information and could be used instead of TD Client. PMID- 22777858 TI - Higher scrotal uptake ratio of (99m)Tc-MDP on bone scans in newly diagnosed prostate cancer: a reliable indicator of pelvic node metastasis. AB - OBJECTIVE: Pelvic lymph node dissection (PLND) is the gold standard procedure for nodal staging in prostate cancer (PC) but less commonly used due to its invasiveness. More commonly computerized tomography (CT) and magnetic resonance imaging (MRI) are used although these have limited sensitivities and specificities. The aim of this study was to find out the correlation between higher scrotal uptake ratio (SUR) of (99m)Tc-methylene diphosphonate (MDP) on bone scan and pelvic node metastasis in patients with PC at high risk for nodal metastasis. METHODS: This was a retrospective study which included 68 biopsy proven newly diagnosed PC patients who had bone scan from January 2008 till January 2012. MRI of the pelvis, prostate specific antigen (PSA) and Gleason's score were available in all patients. Whole body bone scan was performed in all patients and SUR was calculated by dividing mean counts over scrotum and soft tissue over lateral aspect of right thigh. PLND was carried out within 2-3 weeks of MRI study in these patients. RESULTS: Mean age of studied males was 71 +/- 07 years with a mean PSA level of 65 +/- 162 ng/ml. Prostate biopsy revealed adenocarcinoma in all patients with mean Gleason's score 7 +/- 1. Mean SUR was 2.786 +/- 0.496. MRI was positive for pelvic lymphadenopathy in 32/68 (47 %). PLND revealed evidence of nodal metastasis in 16/68 (24 %) patients. Receiver operating characteristic analysis revealed good diagnostic strength of SUR for nodal metastasis with a cut off value of >2.99 with an area under curve (AUC) 0.708 (95 % CI 0.533-0.847, p value <0.05) and a mean sensitivity of 68.75 % and mean specificity of 80 %. Diagnostic strength of MRI for nodal metastasis was found to be low (AUC 0.566, 95 % CI 0.047-0.657, non-significant p value). No significant correlation was found between SUR and PSA in nodes positive and nodes negative patients. CONCLUSION: We conclude that in newly diagnosed PC patients, higher SUR on bone scan has a high diagnostic accuracy for pelvic node metastasis. Furthermore, a bone scan with a SUR <2.99 and negative for bone metastasis can stratify newly diagnosed PC patients as low risk. PMID- 22777859 TI - Novel method for quantitative evaluation of cardiac amyloidosis using (201)TlCl and (99m)Tc-PYP SPECT. AB - OBJECTIVE: The degree of myocardial technetium-(99m)-pyrophosphate ((99m)Tc-PYP) accumulation in cardiac amyloidosis is conventionally evaluated by the PYP score. This method involves qualitative visual evaluation on two-dimensional images. Here, we performed three-dimensional quantitative analysis using software developed in our laboratory. METHODS: We performed dual myocardial imaging using thallium-(201)-chloride ((201)Tl-Cl) and (99m)Tc-PYP in cases of suspected cardiac amyloidosis and calculated the PYP accumulation rates of all myocardial pixels showing (99m)Tc-PYP accumulation. We defined this procedure as quantitative evaluation of the degree of (99m)Tc-PYP accumulation in the myocardium. Patients were divided into two groups with and without a diagnosis of cardiac amyloidosis, and we examined the PYP accumulation rates in both groups. In addition, we examined the PYP scores of the two groups by conventional qualitative evaluation. RESULTS: The PYP scores of the cardiac amyloidosis group were significantly higher than those of the other group. The PYP accumulation rates of the cardiac amyloidosis group were significantly higher than those of the other group. There were significant differences in the PYP accumulation rate and PYP score between the two groups. There was considered to be a threshold between the two groups in the case of the PYP accumulation rate. CONCLUSIONS: When the threshold of the PYP score was defined as 3+ and that of the PYP accumulation rate as 41.5 %, the sensitivity of the PYP score and PYP accumulation rate was 84.6 %. However, the specificity of the PYP accumulation rate was higher than that of the PYP score. Quantitative evaluation by the PYP accumulation rate of the degree of (99m)Tc-PYP accumulation in the myocardium may be useful in the diagnosis of cardiac amyloidosis. PMID- 22777860 TI - A steep price. AB - Texas physicians fear that sharp funding cuts in state family planning services and changes in a state health program for women will threaten women's access to vital preventive services. They say the situation is a crisis and urge lawmakers to restore money to programs that provide low-income women with recommended screenings and birth control. PMID- 22777861 TI - A tough call. AB - Physicians may consider opting out of Medicare because of low pay and increasing hassles. Formally opting out of Medicare means a physician cannot bill Medicare at all for the care he or she provides a Medicare beneficiary. And Medicare will not reimburse a patient for any out-of-pocket expenses incurred in seeing an opted-out physician. Physicians who opt out of Medicare must do so for two years. Then they must decide if they want to opt out for another two years or rejoin the program. PMID- 22777862 TI - Zip it! AB - When it comes to enforcing HIPAA data security and privacy standards, the federal government means business. In fact, the government is conducting a national pilot program to audit 150 physicians and others that HIPAA covers as the first phase of a concerted effort to crack down on HIPAA violations. PMID- 22777863 TI - Safety concerns. AB - Current University Interscholastic League rules allow physicians, physician assistants, nurse practitioners, and chiropractors to perform physicals. But a special Texas Medical Association subcommittee that vetted sports injury-related bills during the last legislative session questions whether chiropractors have the necessary training to adequately conduct sports physicals. In May, the TMA House of Delegates adopted a resolution that says only licensed physicians, or their appropriately supervised physician assistants or advanced practice nurses should perform sports physicals. PMID- 22777864 TI - The past and present of malaria in Houston. AB - Malaria has a long-standing association among diseases that affect Texans and Houstonians. Early records show that in 1935 at least 25,000 cases of malaria were reported in Texas (with at least 1500 in Houston) and that between then and 1959 the largest number occurred in August. A dramatic fall in malaria incidence occurred through the 1930s and 1940s, with a surge at the onset of World War II and very few cases in the 1950s. Texas records report 625 travel-associated cases in Texas from 1952 through 1959. Another 115 case-patients were reported by combining data from Ben Taub General Hospital between 2003 and 2009 and from the City of Houston Health Department between 2005 and 2009. These cases manifested Plasmodium falciparum disease typically among travelers to Africa (85% of recent cases) or Plasmodium vivax among Central American immigrants. Only about one-half of these patients took prophylaxis, and only 1 patient (a Cameroonian) reported having used artemisinin combination therapy. PMID- 22777865 TI - Odanacatib in the treatment of postmenopausal women with low bone mineral density: five years of continued therapy in a phase 2 study. AB - Odanacatib (ODN) is a selective inhibitor of the collagenase cathepsin K that is highly expressed by osteoclasts. In this 2-year, phase 2, dose-ranging trial, postmenopausal women with bone mineral density (BMD) T-scores -2.0 to -3.5 at spine or hip were randomized to weekly placebo or ODN 3, 10, 25, or 50 mg plus vitamin D(3) and calcium. Prespecified trial-extensions continued through 5 years. In year 3, all women were re-randomized to ODN 50 mg or placebo. For years 4 and 5, women who received placebo or ODN 3 mg in years 1 and 2 and placebo in year 3 received ODN 50 mg; others continued year 3 treatments. Endpoints included lumbar spine (primary), hip, 1/3 radius, and total body BMD; markers of bone metabolism; and safety. Women in the year 4 to 5 extension receiving placebo (n = 41) or ODN 50 mg (n = 100) had similar baseline characteristics. For women who received ODN (10-50 mg) for 5 years, spine and hip BMD increased over time. With ODN 50 mg continually for 5 years (n = 13), mean lumbar spine BMD percent change from baseline (95% confidence interval [CI]) was 11.9% (7.2% to 16.5%) versus 0.4% (-3.1% to 2.3%) for women who were switched from ODN 50 mg to placebo after 2 years (n = 14). In pooled results of women receiving continuous ODN (10-50 mg, n = 26-29), year 5 geometric mean percent changes from baseline in bone resorption markers cross-linked N-telopeptide of type I collagen (NTX)/creatinine and cross-linked C-telopeptide (CTX) were approximately -55%, but near baseline for bone formation markers bone-specific alkaline phosphatase (BSAP) and amino terminal propeptide of type I procollagen (P1NP). In women switched from ODN 10 to 50 mg to placebo after 2 years (n = 25), bone turnover markers were near baseline. In summary, women receiving combinations of ODN (10-50 mg) for 5 years had gains in spine and hip BMD and showed larger reductions in bone resorption than bone formation markers. Discontinuation of ODN resulted in reversal of treatment effects. Treatment with ODN for up to 5 years was generally well tolerated. PMID- 22777866 TI - Prognostic factors in sinonasal sarcomas: analysis of the surveillance, epidemiology and end result database. AB - OBJECTIVES/HYPOTHESIS: Sinonasal sarcomas are rare and often aggressive malignant tumors. Although tumor histology and location are the only reported prognostic indicators for this disease, we sought to determine if additional clinical factors might influence patient survival. STUDY DESIGN: Retrospective cohort study using a national cancer database. METHODS: Cases of sinonasal sarcomas from 1973 to 2008 were extracted from the Surveillance, Epidemiology and End Result (SEER) database. The influence of patient age, gender, race, and prior irradiation, as well as tumor histology and subsite, was calculated using the Kaplan-Meier method. RESULTS: A total of 352 patients with sinonasal sarcomas were identified. Histologic subtype, tumor location, gender, and patient age were found to influence patient survival. Specifically, increased age, male sex, frontal and maxillary sinus subsites, and rhabdomyosarcoma and Kaposi sarcoma histologies were associated with a significant increase in mortality rate (P < .05). CONCLUSIONS: This study comprises the largest analysis of patients with sinonasal sarcoma in the literature and demonstrates the impact of patient age, tumor histology, and tumor location on the overall survival of individuals with these rare malignancies. PMID- 22777867 TI - Novel synthesis of leucoside by enzymatic hydrolysis of tea seed extract. AB - BACKGROUND: The application of tea seed extract (TSE) has been widely investigated owing to its biological activities. In this paper, two flavonol triglycosides found in TSE, camelliaside A (CamA) and camelliaside B (CamB), were subjected to hydrolysis in the presence of three commercial enzyme complexes of the Pectinex(r) series, 5XL, XXL and Ultra SP-L (Ultra). RESULTS: XXL and 5XL induced stepwise deglycosylation of CamA and CamB to yield kaempferol diglycoside (nicotiflorin), kaempferol monoglycoside (astragalin) and kaempferol, while Ultra produced an additional new compound (1) that had not been observed in earlier studies. Upon hydrolysis of isolated CamA and CamB, compound (1) was obtained only from CamB. Both the molecular ion peak in liquid chromatography/mass spectrometry and the 1H and 13C nuclear magnetic resonance spectra of (1) isolated by Ultra-induced hydrolysis of TSE indicated that (1) was kaempferol 3-O beta-xylopyranosyl (1 -> 2)-beta-glucopyranoside (leucoside), formed by selective hydrolysis of the rhamnosyl moiety of CamB. CONCLUSION: Pure leucoside can be prepared by enzymatic partial hydrolysis of TSE. This is the first study to address the synthesis of pure leucoside from a natural source. PMID- 22777868 TI - Screening rhodium metallopeptide libraries "on bead": asymmetric cyclopropanation and a solution to the enantiomer problem. AB - Searching with a beady eye: A high-throughput, on-bead screen of rhodium metallopeptide catalysts was developed in a 96-well format for asymmetric cyclopropanation. Different sequences of natural L-amino acids have been identified that produce opposite product enantiomers. In addition to styrene derivatives, high enantioselectivity is observed for vinyl ether and vinyl amine derivatives. PMID- 22777869 TI - The patient, the doctor, and the system: underdiagnosis and undertreatment of hepatitis B. PMID- 22777870 TI - Experimental confirmation of local field enhancement determining far-field measurements with shell-isolated silver nanoparticles. PMID- 22777871 TI - Osteological associations with unique tooth development in manatees (Trichechidae, Sirenia): a detailed look at modern Trichechus and a review of the fossil record. AB - Modern manatees have a unique type of tooth development, continually forming identical new molars in the posterior end of each quadrant of their mouths, and then progressively moving teeth anteriorly, only to reabsorb roots and spit out worn crowns. This process is not only developmentally complex, but requires space in the oral cavity that imposes its own limitations on other uses of that space. To gain a clearer understanding of the anatomical constraints on the evolution of this unique developmental process, we identified the specialized craniodental features in modern Trichechus that permit this specialization using visual observation and CT. Furthermore, to better understand the evolution of these traits, we review the fossil record of trichechids for these traits, including CT analysis of the skull of Miosiren kocki, a possible early member of the family from the Early Miocene of Belgium. PMID- 22777872 TI - Percutaneous coronary intervention in TAVI: the "proboscis" catheter. AB - We report a case of an 81-years-old male, recently implanted with a Core Valve (CV) prosthesis and admitted to the ER for acute coronary syndrome. Coronary angiography revealed the patency of the coronary artery by-pass grafts but was impossible to cannulate the left main "imprisoned" by the CV prosthesis struts. Aortography showed an excessive gap between the CV struts and the coronary ostium. To cross the CV struts, we developed a "proboscis" catheter by cutting away the proximal end of the 7F JL 4 catheter and putting inside the 5F Heartrail catheter. The following angiograms showed a critical stenosis in the proximal obtuse marginal (branch), successfully treated with a bare-metal stent implantation. PMID- 22777873 TI - Acidic metabolite profiling analysis of catecholamine and serotonin as O ethoxycarbonyl/tert-butyldimethylsilyl derivatives by gas chromatography-mass spectrometry. AB - A novel derivatization method was developed for the simultaneous determination of six acidic metabolites of catecholamine and serotonin by gas chromatography-mass spectrometry (GC-MS). The metabolites were converted to O-ethoxycarbonyl/tert butyldimethylsilyl (EOC/TBDMS) derivatives for the direct GC-MS analysis in selected ion monitoring mode. Their mass spectral pattern as EOC/TBDMS derivatives showed characteristic fragment ions of [M - 15](+) and [M - 57](+), which permitted rapid and accurate structural confirmation of acidic metabolites. The present method was linear (r >= 0.998), reproducible (percentage relative standard deviation = 1.0-10.0) and accurate (% relative error = -9.7-9.8) with detection limits of 0.001-4.7 ng/mL. When applied to human urine samples, the method allowed simultaneous determination of six acidic metabolites of catecholamine and serotonin. PMID- 22777875 TI - Systematic review and meta-analysis of wound dressings in the prevention of surgical-site infections in surgical wounds healing by primary intention. AB - BACKGROUND: Postoperative surgical-site infections are a major source of morbidity and cost. This study aimed to identify and present all randomized controlled trial evidence evaluating the effects of dressings on surgical-site infection rates in surgical wounds healing by primary intention; the secondary outcomes included comparisons of pain, scar and acceptability between dressings. METHODS: Randomized controlled trials comparing alternative wound dressings, or wound dressings with leaving wounds exposed for postoperative management of surgical wounds were included in the review regardless of their language. Databases searched included the Cochrane Wounds Group Specialised Register and Central Register of Controlled Trials, Ovid MEDLINE, Ovid Embase and EBSCO CINAHL from inception to May 2011. Two authors performed study selection, risk of bias assessment and data extraction, including an assessment of surgical contamination according to the surgical procedure. Where levels of clinical and statistical heterogeneity permitted, data were pooled for meta-analysis. RESULTS: Sixteen controlled trials with 2594 participants examining a range of wound contamination levels were included. They were all unclear or at high risk of bias. There was no evidence that any dressing significantly reduced surgical-site infection rates compared with any other dressing or leaving the wound exposed. Furthermore, no significant differences in pain, scarring or acceptability were seen between the dressings. CONCLUSION: No difference in surgical-site infection rates was demonstrated between surgical wounds covered with different dressings and those left uncovered. No difference was seen in pain, scar or acceptability between dressings. PMID- 22777874 TI - Electrostatics of cysteine residues in proteins: parameterization and validation of a simple model. AB - One of the most popular and simple models for the calculation of pK(a) s from a protein structure is the semi-macroscopic electrostatic model MEAD. This model requires empirical parameters for each residue to calculate pK(a) s. Analysis of current, widely used empirical parameters for cysteine residues showed that they did not reproduce expected cysteine pK(a) s; thus, we set out to identify parameters consistent with the CHARMM27 force field that capture both the behavior of typical cysteines in proteins and the behavior of cysteines which have perturbed pK(a) s. The new parameters were validated in three ways: (1) calculation across a large set of typical cysteines in proteins (where the calculations are expected to reproduce expected ensemble behavior); (2) calculation across a set of perturbed cysteines in proteins (where the calculations are expected to reproduce the shifted ensemble behavior); and (3) comparison to experimentally determined pK(a) values (where the calculation should reproduce the pK(a) within experimental error). Both the general behavior of cysteines in proteins and the perturbed pK(a) in some proteins can be predicted reasonably well using the newly determined empirical parameters within the MEAD model for protein electrostatics. This study provides the first general analysis of the electrostatics of cysteines in proteins, with specific attention paid to capturing both the behavior of typical cysteines in a protein and the behavior of cysteines whose pK(a) should be shifted, and validation of force field parameters for cysteine residues. PMID- 22777876 TI - The vaccine adjuvant alum inhibits IL-12 by promoting PI3 kinase signaling while chitosan does not inhibit IL-12 and enhances Th1 and Th17 responses. AB - Alum is the principal vaccine adjuvant for clinical applications but it is a poor inducer of cellular immunity and is not an optimal adjuvant for vaccines where Th1 responses are required for protection. The mechanism underlying the inefficiency of alum in promoting Th1 responses is not fully understood. We show that aluminium hydroxide, aluminium phosphate, and calcium phosphate adjuvants inhibit the secretion of the Th1 polarizing cytokine, IL-12 by dendritic cells (DCs). Alum selectively inhibited DC expression of the IL-12p35 subunit and the inhibitory effect results from adjuvant-induced PI3 kinase signaling. To develop a more effective adjuvant for promoting cell-mediated immunity, we investigated alternative particulates and found that in contrast to alum, the cationic polysaccharide chitosan did not inhibit IL-12 secretion. A combination of chitosan and the TLR9 agonist CpG activated the NLRP3 inflammasome and enhanced secretion of IL-12 and the other key Th1 and Th17-cell polarizing cytokines. When used as an adjuvant, CpG-chitosan induced NLRP3-dependent antigen-specific Th1 and Th17 responses. A combination of alum and CpG also enhanced Th1 and Th17 responses but was less effective than CpG-chitosan. Therefore, chitosan is an attractive alternative to alum in adjuvants for vaccines where potent cell mediated immunity is required. PMID- 22777877 TI - Assessment of the liver strain among cirrhotic and normal livers using tagged MRI. AB - PURPOSE: To use magnetization tagged magnetic resonance imaging (MRI) (tag-MRI) to quantify cardiac induced liver strain and compare strain of cirrhotic and normal livers. MATERIALS AND METHODS: Tag-MRI was performed at 1.5T on eight subjects with no history of liver disease and 10 patients with liver cirrhosis. A breath-hold peripheral pulse-gated (PPG) conventional tag-MRI cine sequence was performed with planes to include the left lobe of the liver and the inferior wall of the heart. Commercially available software HARP (Diagnosoft, Palo Alto, CA) was used for image analysis and strain calculation. Three regions-of-interest (ROIs) were selected: segment II of the liver near the heart (A), right liver lobe far from the heart (B), and the left ventricular wall (C). The average and maximal (max) strain were measured in A, B, and C. The maximum strains were used to generate a cardiac-corrected strain gradient: (maxA-maxB)/maxC. Results were compared with Student's t-test (SPSS, Chicago, IL). RESULTS: In subjects with no history of liver disease vs. cirrhotic patients, the average strain was 22% +/- 7% vs. 4% +/- 3% (P < 0.001), the max strain was 63% +/- 15% vs. 17% +/- 5% (P < 0.001), and the corrected strain gradient was 0.52 +/- 0.16 vs. 0.11% +/- 0.08%. CONCLUSION: There is a significant difference in liver strain measured with tag MRI between subjects with no history of liver disease and patients with cirrhosis. PMID- 22777878 TI - A psychoeducational intervention (SWEEP) for depressed women with diabetes. AB - BACKGROUND: Clinically significant depression is present in 25 % of individuals with type 2 diabetes, its risk being doubled in women. PURPOSE: To examine the effectiveness of the Study of Women's Emotions and Evaluation of a Psychoeducational (SWEEP), a group therapy for depression treatment based on cognitive behavioral therapy principles that was developed for women with type 2 diabetes was conducted. METHODS: Women with significantly elevated depression symptoms (Center for Epidemiologic Studies Depression Scale >=16) were randomized to SWEEP (n = 38) or usual care (UC, n = 36). RESULTS: Multilevel modeling indicated that SWEEP was more effective than UC in reducing depression (mean difference of -15 vs. -7, p < .01), decreasing trait anxiety (mean difference of 15 vs. -5, p < .01), and improving anger expression (mean difference of -12 vs. 5, p < .05). Although SWEEP and UC had improvements in fasting glucose (mean difference of -24 vs. -1 mg/dl) and HbA1c (mean difference of -0.4 vs. -0.1 %), there were no statistically significant differences between groups. CONCLUSIONS: SWEEP was more effective than UC for treating depressed women with type 2 diabetes. Addition of group therapy for depression meaningfully expands the armamentarium of evidence-based treatment options for women with diabetes. PMID- 22777879 TI - The built environment moderates effects of family-based childhood obesity treatment over 2 years. AB - BACKGROUND: Research suggests the neighborhood built environment is related to child physical activity and eating. PURPOSE: The purpose of this study was to determine if characteristics of the neighborhood environment moderate the relationship between obesity treatment and weight loss, and if outcomes of particular treatments are moderated by built environment characteristics. METHOD: The relationship between the built environment and standardized BMI (zBMI) changes for 191 8-12-year-old children who participated in one of four randomized, controlled trials of pediatric weight management was assessed using mixed models analysis of covariance. RESULTS: At 2-year follow-up, greater parkland, fewer convenience stores, and fewer supermarkets were associated with greater zBMI reduction across all interventions. No treatments interacted with characteristics of the built environment. CONCLUSIONS: Activity- and eating related built neighborhood characteristics are associated with child success in behavioral obesity treatments. Efficacy may be improved by individualizing treatments based on built environment characteristics. PMID- 22777881 TI - The effect of pneumonia on short-term outcomes and cost of care after head and neck cancer surgery. AB - BACKGROUND: The Centers for Medicare and Medicaid Services has threatened to discontinue reimbursements for ventilator-associated pneumonia (VAP) as a preventable "never event." We sought to determine the relationship between pneumonia and in-hospital mortality, complications, length of hospitalization and costs in head and neck cancer (HNCA) surgery. STUDY DESIGN: Retrospective cross sectional study. METHODS: Discharge data from the Nationwide Inpatient Sample for 93,663 patients who underwent an ablative procedure for a malignant oral cavity, laryngeal, hypopharyngeal, or oropharyngeal neoplasm from 2003 to 2008 were analyzed using cross-tabulations and multivariate regression modeling. RESULTS: VAP was rarely coded. Infectious pneumonia was significantly associated with chronic pulmonary disease (odds ratio [OR], 1.5; P < .001), while aspiration pneumonia was associated with dysphagia (OR, 2.0; P < .001). Pneumonia from any cause was associated with weight loss (OR, 3.3; P < .001), age >80 years (OR, 2.0; P = .007), comorbidity (OR, 2.3; P < .001), and major procedures (OR, 1.6; P < .001), with increased in-hospital mortality for infectious (OR, 2.9; P < .001) and aspiration pneumonia (OR, 5.3; P < .001). Both infectious and aspiration pneumonia were associated with postoperative medical and surgical complications, increased length of hospitalization, and hospital-related costs. CONCLUSIONS: Postoperative pneumonia is associated with increased mortality, complications, length of hospitalization, and hospital-related costs in HNCA surgical patients. Variables associated with an increased risk of pneumonia are inherent comorbidities in HNCA and known risk factors for VAP, making this a high-risk group for this never event. Caution must be used in the institution of reforms that threaten to inadequately reimburse the provision of care to this vulnerable population. Aggressive preoperative identification and treatment of underlying pulmonary disease, weight loss, and dysphagia may reduce morbidity and mortality. PMID- 22777880 TI - Socioeconomic status, nocturnal blood pressure dipping, and psychosocial factors: a cross-sectional investigation in Mexican-American women. AB - BACKGROUND: Despite established links between reduced nocturnal blood pressure (BP) dipping and cardiovascular disease, BP dipping research in Hispanics is limited. PURPOSE: This study investigated socioeconomic status (SES) as a predictor of BP dipping and the contributions of psychosocial factors to this relationship. Analyses were conducted for the overall sample and separately for higher and lower acculturated women. METHODS: Mexican-American women (N = 291; 40 65 years) reported demographics and completed psychosocial assessments and 36-h ambulatory BP monitoring. RESULTS: Lower SES related to reduced BP dipping in the overall sample and in more US-acculturated women (r's = .17-.30, p's < .05), but not in less-acculturated women (r's = .07, p's > .10). An indirect effect model from SES to BP dipping via psychosocial resources/risk fits well across samples. CONCLUSIONS: In Mexican-American women, the nature of SES gradients in BP dipping and the roles of psychosocial resources/risk differ by acculturation level. PMID- 22777882 TI - Prediction of distal embolization during percutaneous coronary intervention for unstable plaques with grayscale and integrated backscatter intravascular ultrasound. AB - OBJECTIVES: We performed microscopic examination of the debris collected by a distal protection device and investigated the usefulness of grayscale and integrated backscatter intravascular ultrasound (IB-IVUS) for the prediction of distal embolization during percutaneous coronary intervention (PCI) in cases of unstable angina. BACKGROUND: The prediction of distal embolization during PCI has not been studied in depth because assessment of distal embolization is difficult. METHODS: We prospectively studied 39 consecutive patients with unstable angina who underwent PCI with a filter distal protection device. The preprocedural plaque volume at target lesions was measured with grayscale IVUS and plaque characteristics were assessed with IB-IVUS. We performed microscopic examination of the particles collected by the distal protection device. RESULTS: There was a significant correlation between the plaque volume and the number of the collected particles >100 MUm in diameter (r = 0.48, P = 0.0034). Filter no-reflow (FNR) phenomenon was found in nine patients. The plaque volume was significantly greater (355 +/- 133 mm(3) vs. 199 +/- 90 mm(3) , P = 0.0004), and the lipid ratio was significantly higher (29.3 +/- 4.3% vs. 26.1 +/- 4.3 P = 0.045) in the FNR group compared with the non-FNR group. Multivariate logistic regression analysis showed that the plaque volume was an independent predictor of FNR phenomenon. CONCLUSIONS: Although tissue characterization of IB-IVUS may provide additional information for distal embolization, plaque volume is the only significant predictor of distal embolization during PCI. PMID- 22777883 TI - Enriched environment and white matter in aging brain. AB - Normal aging is commonly associated with decreased cognitive functions, which could be conspicuously alleviated by enriched environment (EE) with physical, social, and sensory stimuli, suggesting that aging brain still has intriguing plasticity. Multiple researches have been carried out to explore the structural and the molecular changes in aging brain, which would be considered for evidences that EE regulated brain plasticity. Because there is no significant neuron loss in aging cerebral cortex and the white matter is crucial for cognitive functions, this review focused on the age-related white matter changes and the effects of EE on aged white matter. Data from our stereology laboratory revealed that age related spatial memory declines had more to do with white matter alterations, which were due to marked demyelination and loss of oligodendrocytes in the white matter. We also demonstrated that EE recovered spatial memory impairment and increased white matter volume by promoting marked remyelination in aged brain. This review approached the issue that EE might contribute to normal aging and be beneficial for those suffering from demyelinated diseases. PMID- 22777884 TI - Novel indanone derivatives as potential imaging probes for beta-amyloid plaques in the brain. AB - Molecular imaging probes to detect senile plaques (SPs) might help the early diagnosis of Alzheimer's disease (AD). In this study, a novel series of indanone derivatives were synthesized and characterized. In in vitro binding studies, compound 2e exhibited a K(i) value of 16 nM with a human AD brain homogenate. Although they displayed relatively low affinities for 2i and 2j--with K(i) values of 99 and 237 nM, respectively--the SPs in AD brain sections were positively stained by 2j. A method for in situ micro-autoradiography of AD brain was developed in this study and showed clear labeling of SPs by [(125)I]2i and [(125)I]2j. Both [(125)I]2i and [(125)I]2j had suitable lipophilicities and displayed high initial uptake and rapid clearance from the mouse brains. Furthermore, [(125)I]2i and [(125)I]2j were more stable in human brain homogenates than in mouse brain homogenates. These data suggest that such indanone derivatives might represent potential amyloid imaging agents for the detection of SPs in AD. PMID- 22777885 TI - [The 'red puffy ear sign'--a clinical sign to diagnose a rare cause of meningoencephalitis]. AB - We report on the case of a 63-year-old patient with a meningoencephalitis, presenting itself with headache and a general neuropsychological retardation. Additionally, a reddening and swelling of both auricles could be seen. Magnetic resonance imaging showed confluent, contrast-uptaking lesions. In the cerebrospinal fluid an aseptic lymphocytic pleocytosis was found. A biopsy of the ear revealed a chronic lymphoplasmacellular inflammatory reaction. We diagnosed a relapsing polychrondritis, an inflammatory disease of the cartilage, which can in rare cases affect the central nervous system. Typically, the patients complain about red swollen ears, the "red puffy ear sign". After initiation of steroid and azathioprin therapy the patient recovered fully. PMID- 22777886 TI - Recent advances in targeted genome engineering in mammalian systems. AB - Targeted genome engineering enables researchers to disrupt, insert, or replace a genomic sequence precisely at a predetermined locus. One well-established technology to edit a mammalian genome is known as gene targeting, which is based on the homologous recombination (HR) mechanism. However, the low HR frequency in mammalian cells (except for mice) prevents its wide application. To address this limitation, a custom-designed nuclease is used to introduce a site-specific DNA double-strand break (DSB) on the chromosome and the subsequent repair of the DSB by the HR mechanism or the non-homologous end joining mechanism results in efficient targeted genome modifications. Engineered homing endonucleases (also called meganucleases), zinc finger nucleases, and transcription activator-like effector nucleases represent the three major classes of custom-designed nucleases that have been successfully applied in many different organisms for targeted genome engineering. This article reviews the recent developments of these genome engineering tools and highlights a few representative applications in mammalian systems. Recent advances in gene delivery strategies of these custom-designed nucleases are also briefly discussed. PMID- 22777887 TI - Predominance of heterosubtypic IFN-gamma-only-secreting effector memory T cells in pandemic H1N1 naive adults. AB - The 2009/10 pandemic (pH1N1) highlighted the need for vaccines conferring heterosubtypic immunity against antigenically shifted influenza strains. Although cross-reactive T cells are strong candidates for mediating heterosubtypic immunity, little is known about the population-level prevalence, frequency, and cytokine-secretion profile of heterosubtypic T cells to pH1N1. To assess this, pH1N1 sero-negative adults were recruited. Single-cell IFN-gamma and IL-2 cytokine-secretion profiles to internal proteins of pH1N1 or live virus were enumerated and characterised. Heterosubtypic T cells recognising pH1N1 core proteins were widely prevalent, being detected in 90% (30 of 33) of pH1N1-naive individuals. Although the last exposure to influenza was greater than 6 months ago, the frequency and proportion of the IFN-gamma-only-secreting T-cell subset was significantly higher than the IL-2-only-secreting subset. CD8(+) IFN-gamma only-secreting heterosubtypic T cells were predominantly CCR7(-) CD45RA(-) effector-memory phenotype, expressing the tissue-homing receptor CXCR3 and degranulation marker CD107. Receipt of the 2008-09 influenza vaccine did not alter the frequency of these heterosubtypic T cells, highlighting the inability of current vaccines to maintain this heterosubtypic T-cell pool. The surprisingly high prevalence of pre-existing circulating pH1N1-specific CD8(+) IFN-gamma-only secreting effector memory T cells with cytotoxic and lung-homing potential in pH1N1-seronegative adults may partly explain the low case fatality rate despite high rates of infection of the pandemic in young adults. PMID- 22777889 TI - Simultaneous observation of the lever arm and head explains myosin VI dual function. AB - Myosin VI is an adenosine triphosphate (ATP)-driven dimeric molecular motor that has dual function as a vesicle transporter and a cytoskeletal anchor. Recently, it was reported that myosin VI generates three types of steps by taking either a distant binding or adjacent binding state (noncanonical hand-over-hand step pathway). The adjacent binding state, in which both heads bind to an actin filament near one another, is unique to myosin VI and therefore may help explain its distinct features. However, detailed information of the adjacent binding state remains unclear. Here simultaneous observations of the head and tail domain during stepping are presented. These observations show that the lever arms tilt forward in the adjacent binding state. Furthermore, it is revealed that either head could take the subsequent step with equal probability from this state. Together with previous results, a comprehensive stepping scheme is proposed; it includes the tail domain motion to explain how myosin VI achieves its dual function. PMID- 22777888 TI - The postnatal role of Sox9 in cartilage. AB - Sox9 is an essential transcription factor for the differentiation of the chondrocytic lineage during embryonic development. To test whether Sox9 continues to play a critical role in cartilaginous tissues in the adult mice, we used an inducible, genetic strategy to disrupt the Sox9 gene postnatally in these tissues. The postnatal inactivation of Sox9 led to stunted growth characterized by decreased proliferation, increased cell death, and dedifferentiation of growth plate chondrocytes. Upon postnatal Sox9 inactivation in the articular cartilage, the sulfated proteoglycan and aggrecan content of the uncalcified cartilage were rapidly depleted and the degradation of aggrecan was accompanied by higher ADAMTS5 immunostaining and increased detection of the aggrecan neoepitope, NITEGE. In spite of the severe loss of Collagen 2a1 mRNA, the Collagen II protein persisted in the articular cartilage, and no histopathological signs of osteoarthritis were observed. The homeostasis of the intervertebral disk (IVD) was dramatically altered upon Sox9 depletion, resulting in disk compression and subsequent degeneration. Inactivation of Sox9 in the IVD markedly reduced the expression of several genes encoding extracellular matrix proteins, as well as some of the enzymes responsible for their posttranslational modification. Furthermore, the loss of Sox9 in the IVD decreased the expression of cytokines, cell-surface receptors, and ion channels, suggesting that Sox9 coordinates a large genetic program that is instrumental for the proper homeostasis of the cells contained in the IVD postnatally. Our results indicate that Sox9 has an essential role in the physiological control of cartilaginous tissues in adult mice. (c) 2012 American Society for Bone and Mineral Research. PMID- 22777890 TI - The effects of fruit maturation, delayed storage and ethylene treatment on the incidence of low-temperature breakdown of 'Hayward' kiwifruit. AB - BACKGROUND: Low-temperature breakdown (LTB), a disorder inducing quality loss, during and after cold storage of 'Hayward' kiwifruit was investigated. Harvested kiwifruits during fruit maturation or after delayed storage (DS) at 20 degrees C for 0, 1, 2, 3 and 4 weeks and 1 uL L-1 ethylene treatment for 24 h were stored at -0.5 degrees C for 24 weeks and additional ripening at 20 degrees C for 5 days. Fruit quality indices and LTB incidence and severity were determined before and after treatments. RESULTS: Harvested fruits ripened during maturation, DS and after ethylene treatment. After storage and shelf life, fruits of all treatments were at complete ripening stage. LTB incidence of early harvested fruits was high, while that of fruits of the mid (third) and late harvests was low. Fruits of the third harvest date showed progressively increased LTB incidence with increasing duration of DS to as high as 95-100% after 4 weeks. Ethylene-treated fruits showed a comparable increase in LTB to that corresponding to 2-3 weeks of DS. CONCLUSION: In contrast to fruit maturation, postharvest (after harvest and before storage) DS at non-chilling temperature and ethylene treatment advanced the ripening of 'Hayward' kiwifruit and resulted in increased LTB incidence. PMID- 22777891 TI - The influence of supervision on manual adherence and therapeutic processes. AB - OBJECTIVES: To identify the effectiveness of psychotherapy supervision on therapists' immediate (next session) and long-term (1 year) adherence to time limited dynamic psychotherapy (TLDP). METHOD: Sixteen therapists from the Vanderbilt II psychotherapy project were assigned new cases in pretraining, training, and booster/posttraining year-long cohorts. Technical adherence to the manual, as well as general therapeutic relational processes, were rated for clinical supervisory sessions in which the third therapy session was discussed. The therapy sessions immediately before and after the supervisory sessions were also rated for technical adherence and relational processes. RESULTS: Postsupervision adherence increased from the presupervision session during the training cohort. In supervision, therapists' discussion of techniques and strategies from the manual in supervision was significantly related to technical adherence in the session prior to (but not after) supervision. However, supervisors' discussion of specific techniques predicted therapists' total technical adherence in the therapy session after (but not before) supervision. In terms of the type of techniques, supervisors' influenced postsupervision therapy adherence on TLDP's unique approach to formulation, the cyclical maladaptive pattern, but did not influence technical adherence on the therapeutic relationship. CONCLUSIONS: In supervision, therapists tend to focus on how they adhered to techniques from the previous session, whereas supervisors' comments about specific techniques predicted how the therapist would adhere to techniques in the next therapy session. The findings provide support for the immediate effects of supervision in shaping therapist techniques as well as highlighting the challenges of altering common relational processes through technical training. PMID- 22777892 TI - Synthesis and reactivity of a cationic platinum(II) alkylidene complex. PMID- 22777893 TI - Basal and stress-induced Hsp70 are modulated by ataxin-3. AB - Regulation of basal and induced levels of hsp70 is critical for cellular homeostasis. Ataxin-3 is a deubiquitinase with several cellular functions including transcriptional regulation and maintenance of protein homeostasis. While investigating potential roles of ataxin-3 in response to cellular stress, it appeared that ataxin-3 regulated hsp70. Basal levels of hsp70 were lower in ataxin-3 knockout (KO) mouse brain from 2 to 63 weeks of age and hsp70 was also lower in fibroblasts from ataxin-3 KO mice. Transfecting KO cells with ataxin-3 rescued basal levels of hsp70 protein. Western blots of representative chaperones including hsp110, hsp90, hsp70, hsc70, hsp60, hsp40/hdj2, and hsp25 indicated that only hsp70 was appreciably altered in KO fibroblasts and KO mouse brain. Turnover of hsp70 protein was similar in wild-type (WT) and KO cells; however, basal hsp70 promoter reporter activity was decreased in ataxin-3 KO cells. Transfecting ataxin-3 restored hsp70 basal promoter activity in KO fibroblasts to levels of promoter activity in WT cells; however, mutations that inactivated deubiquitinase activity or the ubiquitin interacting motifs did not restore full activity to hsp70 basal promoter activity. Hsp70 protein and promoter activity were higher in WT compared to KO cells exposed to heat shock and azetidine-2 carboxylic acid, but WT and KO cells had similar levels in response to cadmium. Heat shock factor-1 had decreased levels and increased turnover in ataxin-3 KO fibroblasts. Data in this study are consistent with ataxin-3 regulating basal level of hsp70 as well as modulating hsp70 in response to a subset of cellular stresses. PMID- 22777894 TI - Heat shock enhances the expression of cytotoxic granule proteins and augments the activities of tumor-associated antigen-specific cytotoxic T lymphocytes. AB - Focal inflammation causes systemic fever. Cancer hyperthermia therapy results in shrinkage of tumors by various mechanisms, including induction of adaptive immune response. However, the physiological meaning of systemic fever and mechanisms of tumor shrinkage by hyperthermia have not been completely understood. In this study, we investigated how heat shock influences the adaptive immune system. We established a cytotoxic T lymphocyte (CTL) clone (#IM29) specific for survivin, one of the tumor-associated antigens (TAAs), from survivin peptide-immunized cancer patients' peripheral blood, and the CTL activities were investigated in several temperature conditions (37-41 degrees C). Cytotoxicity and IFN-gamma secretion of CTL were greatest under 39 degrees C condition, whereas they were minimum under 41 degrees C. To address the molecular mechanisms of this phenomenon, we investigated the apoptosis status of CTLs, expression of CD3, CD8, and TCRalphabeta by flow cytometry, and expression of perforin, granzyme B, and Fas ligand by western blot analysis. The expression of perforin and granzyme B were upregulated under temperature conditions of 39 and 41 degrees C. On the other hand, CTL cell death was induced under 41 degrees C condition with highest Caspase-3 activity. Therefore, the greatest cytotoxicity activity at 39 degrees C might depend on upregulation of cytotoxic granule proteins including perforin and granzyme B. These results suggest that heat shock enhances effector phase of the adaptive immune system and promotes eradication of microbe and tumor cells. PMID- 22777895 TI - Reproducibility of measurement of apparent diffusion coefficients of malignant hepatic tumors: effect of DWI techniques and calculation methods. AB - PURPOSE: To evaluate the effect of diffusion-weighted imaging (DWI) methods, apparent diffusion coefficient (ADC) calculation methods, and selection of b values on the ADCs and the measurement reproducibility of malignant hepatic tumors. MATERIALS AND METHODS: Nineteen patients with pathologically confirmed malignant hepatic tumors underwent breath-hold DWI (b-values = 0, 50, 500 s/mm(2)) and respiratory-triggered DWI (0, 50, 300, 500, 1000 s/mm(2)) twice on a 1.5 T magnetic resonance imaging (MRI) scanner. ADCs were calculated using a two b-value and/or a multiple b-value method. The reproducibility of the ADC measurements was evaluated from the intraclass correlation coefficients (ICCs) and the 95% Bland-Altman limit-of-agreement (LOA). RESULTS: The ADCs were different according to the DWI methods (P = 0.040-0.282), ADC calculation methods (P = 0.003-0.825), and the choice of b-values (P < 0.001). The ADC tended to be more reproducible with use of breath-hold DWI (ICC: 0.898-0.933; LOA, 18.8% 24.0%) than respiratory-triggered DWI (ICC: 0.684-0.928; LOA, 15.0%-31.9%) (P = 0.008-0.122). For respiratory-triggered DWI, the multiple b-value method using five b-values had better reproducibility than the two b-value method for measurement of ADC (P = 0.009-0.221). CONCLUSION: The DWI method, ADC calculation method, and selection of b-values potentially influence the ADCs and the reproducibility of malignant hepatic tumors. ADCs calculated from breath-hold DWI are more reproducible than from respiratory-triggered DWI. A multiple b-value method may improve the reproducibility of respiratory-triggered DWI. PMID- 22777897 TI - The axon guidance molecule Netrin-4 is expressed by Muller cells and contributes to angiogenesis in the retina. AB - Retinal glial (Muller) cells are involved in a wide range of developmental mechanisms, including axon guidance and angiogenesis. This study was undertaken to explore whether Netrin-4, an axonal guidance molecule, is expressed by Muller cells and promotes angiogenesis-related activities. Netrin-4 was found through all retinal layers, and its expression was demonstrated in Muller cells, retinal pigment epithelium cells and bovine retinal endothelial cells (BRECs). Co localization of Netrin-4 with Muller cell-specific molecules [cellular retinaldehyde-binding protein (cRALBP), vimentin] was observed in the ganglion cell layer, nerve fiber layer, and at the outer limiting membrane. Under hypoxic conditions, the release of Netrin-4 from Muller cells was increased, with mRNA levels upregulated in a hypoxia-inducible factor-1-dependent manner and dependent on the concomitantly induced release of vascular endothelial growth factor. These findings were consistent with an intensified immunofluorescence of Netrin-4 labeling in the postischemic retinas after ischemia-reperfusion. Netrin-4 stimulated BRECs to increase phosphorylation of the mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK)-1/-2, and p38, in a dose-dependent manner. Synthetic inhibitors of the MAP kinases were able to suppress Netrin-4-induced migration and proliferation of BRECs suggesting that both MAP kinases are differentially involved in Netrin-4-induced angiogenesis. Two receptors for Netrins, i.e., deleted in colorectal cancer (DCC) and uncoordinated-5-homolog 1 (Unc5H1), were detected in BRECs. DCC is at least partially required for Netrin-4-induced activation of ERK-1/-2. These data suggest that Muller glial cells contribute to, and may modulate, retinal Netrin-4 levels. This may be a novel pathway of Muller cell-mediated control of retinal angiogenesis, particularly under hypoxic/ischemic conditions when the cells upregulate Netrin-4 expression. PMID- 22777896 TI - MicroRNA-27b is a regulatory hub in lipid metabolism and is altered in dyslipidemia. AB - Cellular and plasma lipid levels are tightly controlled by complex gene regulatory mechanisms. Elevated plasma lipid content, or hyperlipidemia, is a significant risk factor for cardiovascular morbidity and mortality. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression and have emerged as important modulators of lipid homeostasis, but the extent of their role has not been systematically investigated. In this study we performed high-throughput small RNA sequencing and detected ~ 150 miRNAs in mouse liver. We then employed an unbiased, in silico strategy to identify miRNA regulatory hubs in lipid metabolism, and miR-27b was identified as the strongest such hub in human and mouse liver. In addition, hepatic miR-27b levels were determined to be sensitive to plasma hyperlipidemia, as evidenced by its ~ 3-fold up-regulation in the liver of mice on a high-fat diet (42% calories from fat). Further, we showed in a human hepatocyte cell line (Huh7) that miR-27b regulates the expression (messenger RNA [mRNA] and protein) of several key lipid-metabolism genes, including Angptl3 and Gpam. Finally, we demonstrated that hepatic miR-27b and its target genes are inversely altered in a mouse model of dyslipidemia and atherosclerosis. CONCLUSION: miR-27b is responsive to lipid levels and controls multiple genes critical to dyslipidemia. PMID- 22777898 TI - Associations between the use of critical care procedures and change in functional status at discharge. AB - Quality improvement initiatives in intensive care units (ICUs) have increased survival rates. Changes in functional status following ICU care have been studied, but results are inconclusive because of insufficient consideration of the combinations of critical care procedures used. Using the Japanese administrative database including the Barthel Index (BI) at admission and discharge, we measured the changes in functional status among the adult patients and determined whether longer ICU stay or use of various critical care procedures was associated with functional deterioration. Of the 12 502 528 patients admitted to 1206 hospitals over 5 consecutive years from 2006, we analyzed data from patients aged 15 years or older who survived ICU admission in 320 hospitals. Critical care procedures evaluated were ventilation, blood purification (hemodialysis, hemodiafiltration, or hemadsorption), and cardiac support devices (intra-aortic balloon pump or percutaneous cardiopulmonary support system). Functional outcomes were determined by the difference between BI at admission and at discharge and were divided into improvement, no change, or deterioration. We compared patient characteristics, principal diagnosis, comorbidities, timing of surgical procedure, complications, days in ICU, and use of critical care procedures among the 3 categories. Associations between critical care procedures and functional deterioration were identified using multivariate analysis. Of 234 209 patients with complete BI information, 7137 (3.1%) received blood purification, 27 100 (11.7%) received ventilation, 2888 (1.2%) received blood purification and ventilation, 5613 (2.4%) received a cardiac support device, 247 (0.1%) received a cardiac support device and blood purification, 10 444 (4.5%) received a cardiac support device and ventilation, and 1110 (0.5%) received a cardiac support device, ventilation, and blood purification. Longer use of blood purification or ventilation and a longer ICU stay were associated with functional deterioration. Intensivists should be aware of the effects of critical care procedures on functional deterioration and advance the appropriate use of functional support according to each patient's condition. PMID- 22777899 TI - Bionanotechnology application of polypeptides in a hair color product: self assembly enables expression, processing, and functionality. AB - Bionanotechnology aims to impart new properties to materials from unique functionalities present in biomolecules. However, the promise of bionanotechnology has not materialized beyond the biomedical field due in large part to issues of scalability, purity, and cost of manufacturing. In this work we demonstrate an approach to co-engineer production and system functionality into a single polypeptide. We designed a system to anchor particles onto hair via a multifunctional polypeptide composed of two domains, one with affinity to hair and the other capable of strong interactions with the particle surface. These strong interactions, exemplified by resistance to anionic surfactants, stem from the ability to self-assemble into higher order structures, which were observed by atomic force microscopy. At the same time, the controlled solubility properties of the particle binding domain permit the scalable production in Escherichia coli via inclusion bodies and cost effective purification. We believe this is a significant advance toward the development of bionanotechnology for industrial applications. PMID- 22777900 TI - The effect of Hg2+ on the bioluminescence of Photobacterium leiognathi. AB - Photobacteria were used as test objects for rapid monitoring of ecotoxicants. Specific inhibitory effects of Hg(2+) on bioluminescence and cell growth as well as the lux gene expression of Photobacterium leiognathi were studied. The 3-(4,5 Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay was used to evaluate cellular proliferation and mortality. The luminescent inhibition effect on P. leiognathi cells was found to increase as cellular mortality increased; y = 0.744x - 4.8916, R2 = 0.9794. However, this trend was not observed in cell growth processes. Quantitation of lux mRNAs by semi-quantitative RT-qPCR indicated that increases and decreases in luciferase mRNA integral level coincided with changes in luminescence intensity (R(2) = 0.93). Addition of Hg(2+) changed luminescence but without concomitant changes in extractable luciferase activity. Nevertheless, the presence of Hg(2+) changed lux gene expression. This phenomenon requires further research. PMID- 22777901 TI - Photo-responsive self-assembly of an azobenzene-ended surfactant-encapsulated polyoxometalate complex for modulating catalytic reactions. PMID- 22777903 TI - [Dieter Beckmann in remembrance (1937-2012)]. PMID- 22777902 TI - The association of concurrent vitamin D and sex hormone deficiency with bone loss and fracture risk in older men: the osteoporotic fractures in men (MrOS) study. AB - Low 25-hydroxyvitamin D (VitD), low sex hormones (SH), and high sex hormone binding globulin (SHBG) levels are common in older men. We tested the hypothesis that combinations of low VitD, low SH, and high SHBG would have a synergistic effect on bone mineral density (BMD), bone loss, and fracture risk in older men. Participants were a random subsample of 1468 men (mean age 74 years) from the Osteoporotic Fractures in Men Study (MrOS) plus 278 MrOS men with incident nonspine fractures studied in a case-cohort design. "Abnormal" was defined as lowest quartile for VitD (<20 ng/mL), bioavailable testosterone (BioT, <163 ng/dL), and bioavailable estradiol (BioE, <11 pg/mL); and highest quartile for SHBG (>59 nM). Overall, 10% had isolated VitD deficiency; 40% had only low SH or high SHBG; 15% had both SH/SHBG and VitD abnormality; and 35% had no abnormality. Compared to men with all normal levels, those with both SH/SHBG and VitD abnormality tended to be older, more obese, and to report less physical activity. Isolated VitD deficiency, and low BioT with or without low VitD, was not significantly related to skeletal measures. The combination of VitD deficiency with low BioE and/or high SHBG was associated with significantly lower baseline BMD and higher annualized rates of hip bone loss than SH abnormalities alone or no abnormality. Compared to men with all normal levels, the multivariate-adjusted hazard ratio (95% confidence interval [CI]) for incident nonspine fracture during 4.6-year median follow-up was 1.2 (0.8-1.8) for low VitD alone; 1.3 (0.9-1.9) for low BioE and/or high SHBG alone; and 1.6 (1.1-2.5) for low BioE/high SHBG plus low VitD. In summary, adverse skeletal effects of low sex steroid levels were more pronounced in older men with low VitD levels. The presence of low VitD in the presence of low BioE/high SHBG may contribute substantially to poor skeletal health. PMID- 22777904 TI - [Use of operationalized psychodynamic diagnostics in childhood and adolescence in patients with somatic diseases]. AB - Psychodynamic findings based on the Operationalized Psychodynamic Diagnostics in Childhood and Adolescence (OPD-CA) in patients with Anorectal Malformations (ARM) in comparison to psychiatric patients were presented focussing the psychic structure. Patients with ARM had significant better psychic structure especially with regard to coping with conflicts and communication of affects. Furthermore typical findings were generated: Patients with ARM had better treatment conditions and more positive relationships. Still they had fewer hypotheses about their disease and greater living burden. Structural strengthes facilitate acceptance and integration of the disease. Nonetheless more attention should be paid to child-oriented psychoeducation for development of age-appropriate hypotheses about the disease. Facing living burden, psychological-psychiatric support should be offered to patients with ARM. PMID- 22777905 TI - [Feasibility and acceptance of computer-based assessment for the identification of psychosocially distressed patients in routine clinical care]. AB - This study investigated feasibility and acceptance of computer-based assessment for the identification of psychosocial distress in routine radiotherapy care. 155 cancer patients were assessed using QSC-R10, PO-Bado-SF and Mach-9. The congruence between computerized tablet PC and conventional paper assessment was analysed in 50 patients. The agreement between the 2 modes was high (ICC 0.869 0.980). Acceptance of computer-based assessment was very high (>95%). Sex, age, education, distress and Karnofsky performance status (KPS) did not influence acceptance. Computerized assessment was rated more difficult by older patients (p = 0.039) and patients with low KPS (p = 0.020). 75.5% of the respondents supported referral for psycho-social intervention for distressed patients. The prevalence of distress was 27.1% (QSC-R10). Computer-based assessment allows easy identification of distressed patients. Level of staff involvement is low, and the results are quickly available for care providers. PMID- 22777906 TI - [Attachment-related self evaluation and well-being in the elderly]. AB - The importance of attachment-related self evaluation (German version of the Adult Attachment Scale, AAS) for psychic and physical well-being in elderly aged 60 years or older (N=555; 53% female) was examined. Widowed elderly described themselves as being less able to rely on others, and their need for feeling close to other people was lower than in married elderly. The trust in others and the extent of being afraid of losing an intimate partner predicted age related lower well being. Depressive symptoms in widowed elderly were partly explained by low trust in others. Self-evaluation of attachment reflects psychic resources for well-being in the elderly. PMID- 22777907 TI - [Effect sizes: the clinical relevance of study findings]. PMID- 22777908 TI - Measuring online endorsement of prescription opioids abuse: an integrative methodology. AB - PURPOSE: The ability to track prescription opioid abusers' endorsement of compounds may be valuable in forecasting abuser's preferences. We developed a metric, referred to as the Endorsement Ratio (ERo), to explore the feasibility of quantifying the sentiment expressed by opioid abusers who post online about prescription opioid products. METHODS: Internet posts written between April 1, 2010 and March 31, 2011 and related to six prescription opioid compounds (oxycodone ER, hydrocodone, hydromorphone, oxymorphone, morphine ER, and tramadol) were identified and qualitatively coded. A mixed effects multinomial logistic regression was employed to model the probability of observing endorsing, discouraging, mixed, or unclear messages per compound. Endorsement-to discouragement ratio (ERo) and ratio of endorsement-to-discouragement ratios (RERo) were estimated for each compound. RESULTS: In the study sample of 12 838 Internet posts, a ranking of endorsement could be established, with oxymorphone as most endorsed (ERo = 7.39), followed by hydromorphone (ERo = 5.02), hydrocodone (ERo = 3.53), oxycodone ER (ERo = 3.23), morphine ER (ERo = 2.71), and tramadol (ERo = 1.76). Relative rankings of products required that route of administration be considered. CONCLUSIONS: This study expands existing Internet monitoring approaches by developing a metric to estimate the endorsement of specific prescription opioid compounds as viewed through the lens of Internet communities. Route of administration must be taken into account when examining preferences of drug abusers for various products. This study did not assess whether the novel metric is valid with respect to classification of abuse rates of different drugs. Further studies examining external validation studies are warranted. PMID- 22777909 TI - Rieske iron-sulfur protein of the cytochrome bc(1) complex: a potential target for fungicide discovery. AB - The cytochrome bc(1) complex (complex III, cyt bc(1)) is an essential component of cellular respiration. Cyt bc(1) has three core subunits that are required for its catalytic activity: cytochrome b, cytochrome c(1), and the Rieske iron-sulfur protein (ISP). Although most fungicides inhibit this enzyme by binding to the cytochrome b subunit, resistance to these fungicides has developed rapidly due to their widespread application. Resistance is mainly associated with mutations in cytochrome b, the only subunit encoded by mitochondrial DNA. Recently, the flexibility and motion of the ISP and its essential role in electron transfer have received intense attention; this leads us to propose a new classification of cyt bc(1) inhibitors (three types of Q(o) inhibitors) that mobilize, restrict, or fix the rotation of the ISP. Importantly, the strengths of the ISP-inhibitor interactions correlate with inhibitor activity and the development of resistance to Q(o) inhibitors, thereby offering clues for designing novel cyt bc(1) inhibitors with high potency and a low risk of resistance. PMID- 22777910 TI - B13+ : a photodriven molecular Wankel engine. AB - Revved-up rotary: A molecular Wankel motor, the dual-ring structure B(13)(+), is driven by circularly-polarized infrared electromagnetic radiation. Calculations show that this illumination leads to a guided unidirectional rotation of the outer ring, which is achieved with rotational frequency of the order of 300 GHz. PMID- 22777911 TI - Interaction of TAPP adapter proteins with phosphatidylinositol (3,4)-bisphosphate regulates B-cell activation and autoantibody production. AB - TAPP1 and TAPP2 (where TAPP is tandem PH domain containing protein) are dual PH domain adaptors that selectively bind PI(3,4)P2 (phosphatidylinositol (3,4) bisphosphate). PI(3,4)P2 is a lipid messenger generated by phosphoinositide 3 kinase (PI3K) and SHIP, both of which are critical regulators of B-cell activation. To determine the functional role of TAPP-PI(3,4)P2 interactions, we utilized a double knock-in (KI) mouse bearing mutations within the PI-binding pocket of both TAPP1 and TAPP2. TAPP KI mice show evidence of altered B-cell development, but generate phenotypically normal mature B-cell populations. Total serum immunoglobulin IgM and IgG levels were found to be markedly elevated in TAPP KI mice. B cells purified from TAPP KI mice were hyper-responsive to antigen receptor cross-linking, showing increased proliferation, CD86 expression, and Akt phosphorylation on Ser473 and Thr308. Female TAPP KI mice developed elevated levels of anti-DNA and antinuclear antibodies with age, associated with IgG deposition in kidneys and significant glomerulonephritis pathology. Together our results indicate that interaction of TAPPs with PI(3,4)P2 mediates feedback inhibition impacting on BCR signaling, with functional significance for control of autoreactive B cells. PMID- 22777912 TI - Trends in the use of smokeless tobacco in United States, 2000-2010. AB - OBJECTIVES/HYPOTHESIS: To quantify trends in the use of smokeless tobacco in the United States. STUDY DESIGN: Longitudinal analysis of national population database. METHODS: The National Health Interview Surveys for 2000, 2005, and 2010 were analyzed for adult responses to specific questions regarding smokeless tobacco use, which includes chewing tobacco and snuff. Smokeless tobacco lifetime exposure, current use, and frequency of use were determined according to each sampled year, examining for trends over the past decade. Subset analysis for young adults (ages 18-44 years) was conducted. Demographic factors associated with smokeless tobacco use were also determined. RESULTS: A total of 86,270 adults were surveyed. Among all adults, the proportions of those who had ever tried chewing tobacco were 7.1 +/- 0.2%, 8.5 +/- 0.2%, and 9.2 +/- 0.2% for 2000, 2005, and 2010, respectively (P < .001). Similarly, the proportions of those who had ever tried snuff were 4.4 +/- 0.2%, 7.5 +/- 0.2%, and 8.4 +/- 0.3%, respectively (P < .001). In aggregate, the proportions who were regular users of chewing tobacco remained stable over the survey years: 1.3 +/- 0.1%, 1.1 +/- 0.1%, and 1.2 +/- 0.1%, respectively (P = .382). In contrast, the percentages who were regular users of snuff tobacco increased significantly over the survey years: 1.4 +/- 0.1%, 1.6 +/- 0.1%, and 2.0 +/- 0.1% (P < .001). The proportion of young adults regularly using snuff rose to 2.8 +/- 0.2% (P < .001) in 2010. Male sex, non-Hispanic ethnicity, white race, and less than a high school education were characteristics that were strongly associated with smokeless tobacco use. CONCLUSIONS: There was a trend toward increased smokeless tobacco use, mainly snuff, in the United States in the past decade. This trend was more prominent among young adults and likely will have future health-care implications. PMID- 22777913 TI - Clinical PhD graduate student views of their scientist-practitioner training. AB - OBJECTIVES: The goal of the scientist-practitioner (S-P) training model is to produce clinical psychologists equipped to integrate and utilize both science and practice in the clinical and research domains. However, much has been written regarding the possible shortcomings of S-P training and whether clinical psychology graduate students are actually gaining the knowledge and skills to integrate science and practice during graduate training and beyond (Chang, Lee, & Hargreaves, 2008; Gelso, 2006; Merlo, Collins, & Bernstein, 2008; Phillips, 1993). METHODS: As such, the present study assessed ratings of satisfaction, perception of ability, and use of the S-P training model within 653 clinical psychology graduate students enrolled in programs that are members of the Council of University Directors of Clinical Psychology. RESULTS: Findings suggest that students are consistently trained in the integration of science and practice and have confidence in their abilities to apply the S-P integration to research and clinical work. However, despite understanding the ways in which science can influence practice, over one third of students reported that they rarely use science-based decisions when informing clients of the clinical services they will be providing. CONCLUSIONS: The implications of these results support the need for a more detailed evaluation of clinical psychology graduate students as well as the use of research-informed practice and the process of providing clients with information they need to make informed choices about treatment. PMID- 22777915 TI - Effects of high-pressure processing and enzymatic dephosphorylation on phosvitin properties. AB - BACKGROUND: Egg phosvitin could be a good source of functional peptides. Enzymatic dephosphorylation and high-pressure processing combined with thermal treatment applied before proteolysis could produce phosvitin hydrolysates with different properties compared to its native form. RESULTS: Phosvitin structure was maintained overall during high-pressure treatment of 600 MPa applied at an initial temperature of 65 degrees C regardless of the pH and duration of treatment, confirming the high structural stability of this phosphoprotein. Treatment of phosvitin with phosphatase increased the degree of dephosphorylation from 24% to 63%, after 2 and 18 h, respectively. Moderate dephosphorylation of phosvitin prior to proteolytic digestion improved its hydrolysis, allowing formation of peptides with a molecular weight lower than 17,000 kDa as determined by size exclusion chromatography. Angiotensin-converting enzyme (ACE) inhibition and antioxidant activity of dephosphorylated and protease-treated phosvitin was increased by 52% and 39%, respectively, as compared to protease-digested native phosvitin. CONCLUSION: Enzymatic dephosphorylation before proteolysis mimicking in vivo gut conditions improved ACE inhibition and antioxidant activity of phosvitin hydrolysates. PMID- 22777914 TI - P53 is required for the developmental restriction in Muller glial proliferation in mouse retina. AB - Muller glia are normally mitotically quiescent cells, but in certain pathological states they can re-enter the mitotic cell cycle. While several cell cycle regulators have been shown to be important in this process, a role for the tumor suppressor, p53, has not been demonstrated. Here, we investigated a role for p53 in limiting the ability of Muller glia to proliferate in the mature mouse retina. Our data demonstrate that Muller glia undergo a developmental restriction in their potential to proliferate. Retinal explants or dissociated cultures treated with EGF become mitotically quiescent by the end of the second postnatal week. In contrast, Muller glia from adult trp53-/+ or trp53-/- mice displayed a greater ability to proliferate in response to EGF stimulation in vitro. The enhanced proliferative ability of trp53 deficient mice correlates with a decreased expression of the mitotic inhibitor Cdkn1a/p21(cip) and an increase in c-myc, a transcription factor that promotes cell cycle progression. These data show that p53 plays an essential role in limiting the potential of Muller glia to re-enter the mitotic cycle as the retina matures during postnatal development. PMID- 22777916 TI - Determination of estradiol valerate in pharmaceutical preparations and human serum by flow injection chemiluminescence. AB - A novel method for the detection of trace estradiol valerate (EV) in pharmaceutical preparations and human serum was developed by inhibition of luminol chemiluminescence (CL) by estradiol valerate on the zinc deuteroporphyrin (ZnDP)-enhanced luminol-K3 Fe(CN)6 chemiluminescence system. Under optimized experimental conditions, CL intensity and concentration of estradiol valerate had a good linear relationship in the ranges of 8.0 * 10(-8) to 1.0 * 10(-5) g/mL. Detection limit (3sigma) was estimated to be 3.5 * 10(-8) g/mL. The proposed method was applied successfully for the determination of estradiol valerate in pharmaceutical preparations and human serum and recoveries were 97.0-105.0% and 95.5-106.0%, respectively. The possible mechanism of the CL system is discussed. PMID- 22777917 TI - Wound-healing evaluation of entrapped active agents into protein microspheres over cellulosic gauzes. AB - The use of active ingredients in wound management have evolved alongside the pharmaceutical agents and dressings used to deliver them. However, the development of gauzes, dressings with specific properties, still remains a challenge for several medical applications. A new methodology for the controlled release of active components for the healing of burn wounds is proposed herein. Cotton and non-woven bandages have been cationised to promote the attachment of protein microspheres. The active agents, piroxicam and vegetable oil, were entrapped into the microspheres using ultrasound energy. Active agents were released from the microspheres by a change in pH. Wound healing was assessed through the use of standardised burn wounds induced by a cautery in human full thickness skin equivalents (EpidermFT). The best re-epithelialisation and fastest wound closure was observed in wounds treated with proteinaceous microspheres attached to gauzes, after six days of healing, in comparison with commercial collagen dressing and other controls. Furthermore, the ability of these materials to reduce the inflammation process, together with healing improvement, makes these biomaterials suitable for wound-dressing applications. PMID- 22777918 TI - Decreased expression of SOX7 is correlated with poor prognosis in lung adenocarcinoma patients. AB - Lung adenocarcinoma is the most frequently histologic subtype and the most histologically heterogeneous form of lung cancer. De-regulation of Wnt/beta catenin signaling pathway is implicated in lung carcinogenesis. SOX7, as a member of high mobility group (HMG) transcription factor family, plays a role in the modulation of the Wnt/beta-catenin signaling pathway. However, the expression pattern and clinicopathological significance of SOX7 in patients with lung adenocarcinoma is still unclear. To address this problem, the SOX7 mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemical studies were performed on 288 pairs of adjacent normal lung and lung adenocarcinoma tissues with complete follow-up records. Association of SOX7 protein expression with clinical outcomes was evaluated using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model. SOX7 mRNA expression was significantly down-regulated in lung adenocarcinoma compared with matched adjacent normal tissues (P < 0.001). SOX7 protein was expressed in the cytoplasm of lung adenocarcinoma cells in 106/288 (36.8 %) of cases, whereas its immunoreactivities were predominantly located in the cytoplasm of the adjacent normal tissues. The reduced SOX7 expression was correlated with poor differentiation (P = 0.002), lymph node metastasis (P = 0.011) and advanced TNM stage (P = 0.006). Regarding patient survival, the overall survival and the disease-free survival rates were both significantly lower in patients with SOX7-negative tumors than in those with SOX7-positive tumors (P = 0.018 and 0.013, respectively). Multivariate analysis using a Cox proportional-hazards model demonstrated that SOX7 expression status was an independent prognostic factor predicting the overall survival and the disease-free survival of patients with lung adenocarcinoma (P = 0.021 and 0.016, respectively).Our data suggest that the decreased expression of SOX7 is an important feature of lung adenocarcinoma. The expression level of SOX protein may be a useful prognostic marker for patients with lung adenocarcinoma. PMID- 22777920 TI - Polymer pen lithography using dual-elastomer tip arrays. AB - Dual-elastomer tip arrays are developed as a simple and cost-effective approach to significantly improve the uniformity and precision of polymer pen lithography (PPL). Both experiment and mechanical simulation demonstrate that the hard-apex, soft-base tip structure of the dual-elastomer tip array leads to precise control of feature size and reduced variation among different tips over large areas through fine control of the tip deformation. The dual-elastomer tip array is believed to be readily applied to fabricate nano- and microstructures for fundamental study and applications such as bioassays, sensors, optical and electronic devices. PMID- 22777919 TI - Bone material properties in premenopausal women with idiopathic osteoporosis. AB - Idiopathic osteoporosis (IOP) in premenopausal women is characterized by fragility fractures at low or normal bone mineral density (BMD) in otherwise healthy women with normal gonadal function. Histomorphometric analysis of transiliac bone biopsy samples has revealed microarchitectural deterioration of cancellous bone and thinner cortices. To examine bone material quality, we measured the bone mineralization density distribution (BMDD) in biopsy samples by quantitative backscattered electron imaging (qBEI), and mineral/matrix ratio, mineral crystallinity/maturity, relative proteoglycan content, and collagen cross link ratio at actively bone forming trabecular surfaces by Raman microspectroscopy and Fourier transform infrared microspectroscopy (FTIRM) techniques. The study groups included: premenopausal women with idiopathic fractures (IOP, n = 45), or idiopathic low BMD (Z-score <= -2.0 at spine and/or hip) but no fractures (ILBMD, n = 19), and healthy controls (CONTROL, n = 38). BMDD of cancellous bone showed slightly lower mineral content in IOP (both the average degree of mineralization of cancellous bone [Cn.Ca(Mean) ] and mode calcium concentration [Cn.Ca(Peak) ] are 1.4% lower) and in ILBMD (both are 1.6% lower, p < 0.05) versus CONTROL, but no difference between IOP and ILBMD. Similar differences were found when affected groups were combined versus CONTROL. The differences remained significant after adjustment for cancellous mineralizing surface (MS/BS), suggesting that the reduced mineralization of bone matrix cannot be completely accounted for by differences in bone turnover. Raman microspectroscopy and FTIRM analysis at forming bone surfaces showed no differences between combined IOP/ILBMD groups versus CONTROL, with the exceptions of increased proteoglycan content per mineral content and increased collagen cross-link ratio. When the two affected subgroups were considered individually, mineral/matrix ratio and collagen cross-link ratio were higher in IOP than ILBMD. In conclusion, our findings suggest that bone material properties differ between premenopausal women with IOP/ILBMD and normal controls. In particular, the altered collagen properties at sites of active bone formation support the hypothesis that affected women have osteoblast dysfunction that may play a role in bone fragility. PMID- 22777921 TI - The dehydrogenation of alcohols through a concerted bimetallic mechanism involving an amido-bridged diiridium complex. PMID- 22777922 TI - (19)F MRI monitoring of gene expression in living cells through cell-surface beta lactamase activity. AB - Magnetic resonance imaging provides important intravital information on deep tissues that cannot be visualized by other methods. Although we had previously developed an off/on switching (19)F MRI probe to monitor reporter enzyme activity on the basis of the paramagnetic relaxation enhancement effect, it was difficult to monitor biological events in living cells because the (19)F MRI probe did not permeate living cell membrane. In this study, we have developed a new (19)F MRI system for monitoring gene expression in living cells by exploiting cell-surface displayed beta-lactamase and the specifically designed (19)F MRI probe. By using this system, cellular gene expression was successfully detected by (19)F MRI without cell fixation. This imaging strategy shows promise for monitoring in vivo gene expression, and therefore it could lead to useful technologies for the diagnosis and therapy of various diseases. PMID- 22777923 TI - Endovascular management of symptomatic carotid artery stenosis in a patient with thrombocytopenia. AB - BACKGROUND: Various medical comorbidities such as thrombocytopenia can be obstacles for managing patients with carotid artery disease. PATIENT: We describe our experience with urgent carotid artery stenting for symptomatic carotid artery stenosis in a patient with severe thrombocytopenia. During the treatment, several issues such as mechanism of infarction in carotid artery stenosis, timing of endovascular intervention, and decision making for intervention in patients with thrombocytopenia were discussed. Although the patient experienced complications after carotid artery stenting, he recovered with only mild sequelae. RESULTS AND CONCLUSION: Timely decision is required and individualized treatment strategies should be considered to achieve good results under the given conditions. PMID- 22777924 TI - Exophytic glioblastoma arising from the cerebellum: case report and critical review of the literature. AB - Exophytic glioblastoma arising from the cerebellar tonsil is an extremely rare variant within the possible anatomical presentations of the glioblastoma multiforme (GBM). We report the case of a 55-year-old woman who presented with a tumor located at the cranio-cervical junction with compression of the medulla oblongata and consecutive hydrocephalus. Due to the radiological presentation, the first tentative diagnosis was a meningioma. The tumor was microsurgically removed. Histopathological examination of the tumor revealed a GBM WHO IV. The patient underwent a postoperative percutaneous radiotherapy and concomitant chemotherapy with temozolomide. GBM should be also considered in the differential diagnosis of cerebellar tumors. PMID- 22777925 TI - Case report: Trabecular juvenile ossifying fibroma presenting as a sellar mass. AB - A 15-year-old girl presented with left occulomotor nerve palsy and was found to have a space occupying lesion of the sellar region with invasion of the left cavernous sinus. A transsphenoidal approach lead to subtotal removal of a solid tumor with some remnants in the cavernous sinus and revealed the diagnosis of trabecular juvenile ossifying fibroma (JOF). A repeat magnetic resonance imaging was obtained within 1 month that showed intrasellar recurrence and growing tumor in the cavernous sinus. Therefore, a combined transsphenoidal and transcranial approach was performed to more aggressively remove the tumor. Subsequently, adjuvant proton radiotherapy was performed. JOF of the trabecular type is a rare fibro-osseous lesion of the craniofacial skeleton almost exclusively occurring in the maxilla or the mandible. To our knowledge, this is the first case of this tumor entity presenting as a sellar mass. PMID- 22777926 TI - Fluorescence-guided operation in recurrent glioblastoma multiforme treated with bevacizumab-fluorescence of the noncontrast enhancing tumor tissue? AB - The oral application of 5-aminolevulinic acid (ALA) leads to an accumulation of fluorescent porphyrins in malignant glioma tissue, which simplifies complete tumor resection. If pretreated with bevacizumab, a vascular endothelial growth factor (VEGF) antibody, these patients might not show a contrast enhancement on magnetic resonance imaging (MRI) despite tumor progression. As VEGF antibodies induce a normalization of the tumor vasculature, it is not known whether fluorescence-guided surgery is of any value in patients pretreated with this antibody. One might speculate that missing contrast enhancement on MRI could result in minor or missing fluorescence after the application of ALA. Attempting to give some answers, we report the case of a patient who underwent fluorescence guided reoperation of recurrent glioblastoma multiforme pretreated with bevacizumab. PMID- 22777927 TI - Cervical extradural "en-plaque" meningioma. AB - OBJECTIVE: Spinal meningiomas with concurrent extradural localization and "en plaque" growth are exceptional, with only five reported cases in the literature. We report another case and discuss the peculiar diagnostic and surgical features of this very unusual pattern of growth. CASE REPORT: A 74-year-old woman was observed because of a rapidly progressive tetraparesis, more marked in the left arm. Magnetic resonance imaging depicted an inhomogeneously enhancing tumor of the cervical spine, extending from C4 to T1, with diffuse dural enhancement and extension into the left brachial plexus roots. At operation by laminotomy from C4 to C7 a firm posterior extradural tumor arising from the dura was resected; however, the diffusely infiltrated dura could not be removed. Histology was in favor of a transitional meningioma (WHO I). Postoperatively, irradiation to the operative field with 50 Gy was performed. At follow-up, 18 months after surgery, clinical improvement to moderate tetraparesis was evidenced. CONCLUSIONS: Spinal extradural "en-plaque" meningiomas have been mainly reported in women and at the cervical region, and show extension to many spinal levels as well as diffuse dural infiltration. Preoperatively, they may be differentiated from spinal metastases and lymphomas because of the presence of a "dural tail" sign and calcifications. The surgical resection is mainly limited to the posterior and lateral extradural tumor component, whereas the whole invaded dura is very difficult to resect, mainly in cases with circumferential infiltration. This results in a high rate of tumor recurrence. PMID- 22777928 TI - An extensive intramedullary epidermoid cyst with a longstanding history of paraplegia: a case report. AB - Spinal cord tumors still challenge clinicians because of their neurological deterioration before and after surgery. Epidermoid cyst is one of the rare intramedullary lesions producing neurological deterioration in cervical spine and it has been reported four times in the literature. We report the case of an intramedullary epidermoid cyst showing a longstanding history of paraplegia as well as recent slowly progressive tingling paresthesia extending from C4 to T10 and weakness in both hands. PMID- 22777929 TI - Genetic counseling does not fulfill the counselees' need for certainty in hereditary breast/ovarian cancer families: an explorative assessment. AB - BACKGROUND: Many cancer-patients undergo DNA testing in the BRCA1/2 genes to receive information about the likelihood that cancer is heritable. Previous nonsystematic studies suggested that DNA testing often does not fulfill the counselees' needs for certainty. We explored the balance between the counselees' need for certainty and perceived certainty (NfC-PC, i.e., level of fulfillment of NfC) regarding the specific domains of DNA test result, heredity and cancer. We also examined relationships of NfC-PC with coping styles and distress. METHOD: Before disclosure of BRCA1/2 test results for hereditary breast/ovarian cancer (T1), questionnaires were filled in by 467 cancer-patients. Another questionnaire (T2) was filled in after disclosure of pathogenic mutation results (n = 30), uninformative results (n = 202) or unclassified-variants (n = 16). RESULTS: Before and after DNA test result disclosure, overall 58-94% of all counselees experienced unfulfilled NfC regarding the DNA test result, heredity and cancer. Compared with T1, the communication of pathogenic mutations (T2) caused more fulfillment of the NfC about the DNA test result, but less about cancer and heredity (p < .01). Compared with T1, unclassified variants (T2) did not significantly change the extent of fulfillment of all counselees' needs for certainty (NfC > PC). Compared with T1, uninformative results (T2) caused more fulfillments of all needs than before disclosure (p < 0.01). Counselees differentiated NfC and PC between the domains of DNA-test result, heredity and cancer (p < 0.01). The unfulfilled needs for certainty (NfC-PC) were uncorrelated with cognitive understanding of the DNA test result. CONCLUSION: The counselees' NfC needs more attention in research and practice, for example, when the potential uncertainties of testing are discussed. The counselees' NfC may be assessed and used in tailored, mutual communication of DNA test results. PMID- 22777930 TI - In reference to Tympanic membrane retraction: an endoscopic evaluation of staging systems. PMID- 22777931 TI - Explaining the covariance between attention-deficit hyperactivity disorder symptoms and depressive symptoms: the role of hedonic responsivity. AB - OBJECTIVE: The aim of this study was to examine low hedonic responsivity, a facet of hedonic capacity, as a potential explanatory variable in the relationship between attention deficit/hyperactivity disorder (ADHD) symptoms and depressive symptoms. METHOD: One hundred ninety-eight undergraduate students (mean age = 21.3, standard deviation = 4.6; 59.6% women) from a large, public university completed self-report measures for this cross-sectional study. RESULTS: Results indicated that ADHD symptoms were significantly associated with depressive symptoms, and that low hedonic responsivity partially accounted for this association. This effect was statistically significant for total ADHD symptoms and inattentive symptoms, but not for hyperactive-impulsive symptoms. CONCLUSIONS: Findings are consistent with the possibility that impaired hedonic responsiveness may be a common endophenotype for depression and the inattentive symptoms of ADHD. Implications for future research and clinical work are discussed. PMID- 22777932 TI - Identification of novel glycolipid ligands activating a sulfatide-reactive, CD1d restricted, type II natural killer T lymphocyte. AB - Sulfatide-reactive CD1d-restricted natural killer T (NKT) lymphocytes belong to the type II NKT cell subset with diverse TCRs, and have been found to regulate experimental auto-immune encephalomyelitis, tumor immunity, and experimental hepatitis in murine models. NKT cells can be activated by self-lipids presented by CD1d, manifested as autoreactivity. The identity of most of these self-lipids remains unknown. By isolating lipids from a CD1d-expressing, highly stimulatory antigen presenting cell, we identified isoforms of beta-glucosylceramide (GlcCer), with sphingosine and fatty acid chain lengths of C24:0 and C16:0, that activated a sulfatide-reactive type II NKT cell hybridoma. A screen of structurally related glycosphingolipids demonstrated beta-galactosylceramide (GalCer) as another ligand, and further, that the lysoforms were the most potent isoform of the glycosphingo-lipid ligands, followed by isoforms with a long fatty acid chain of C24. Thus, the same type II NKT cell was activated by several ligands, namely sulfatide, GlcCer, and GalCer. However, CD1d-dependent reactivity to antigen presenting cells lacking all GlcCer-based glycosphingolipids, or all glycosphingolipids, was maintained. This suggests that other endogenous, nonglycosphingolipid, lipid ligands contribute to steady-state autoreactivity by type II NKT cells. PMID- 22777933 TI - Murine recombinant angiotensin-converting enzyme 2: effect on angiotensin II dependent hypertension and distinctive angiotensin-converting enzyme 2 inhibitor characteristics on rodent and human angiotensin-converting enzyme 2. AB - A newly produced murine recombinant angiotensin (Ang)-converting enzyme 2 (ACE2) was characterized in vivo and in vitro. The effects of available ACE2 inhibitors (MLN-4760 and 2 conformational variants of DX600, linear and cyclic) were also examined. When murine ACE2 was given to mice for 4 weeks, a marked increase in serum ACE2 activity was sustainable. In acute studies, mouse ACE2 (1 mg/kg) obliterated hypertension induced by Ang II infusion by rapidly decreasing plasma Ang II. These effects were blocked by MLN-4760 but not by either form of DX600. In vitro, conversion from Ang II to Ang-(1-7) by mouse ACE2 was blocked by MLN 4760 (10(-6) m) but not by either form of DX600 (10(-5) m). Quantitative analysis of multiple Ang peptides in plasma ex vivo revealed formation of Ang-(1-9) from Ang I by human but not by mouse ACE2. Both human and mouse ACE2 led to the dissipation of Ang II with formation of Ang (1-7). By contrast, mouse ACE2-driven Ang-(1-7) formation from Ang II was blocked by MLN-4760 but not by either linear or cyclic DX600. In conclusion, sustained elevations in serum ACE2 activity can be accomplished with murine ACE2 administration, thereby providing a strategy for ACE2 amplification in chronic studies using rodent models of hypertension and cardiovascular disease. Human but not mouse ACE2 degrades Ang I to form Ang-(1 9). There are also species differences regarding rodent and human ACE2 inhibition by known inhibitors such that MLN-4760 inhibits both human and mouse ACE2, whereas DX600 only blocks human ACE2 activity. PMID- 22777934 TI - Impaired increase of retinal capillary blood flow to flicker light exposure in arterial hypertension. AB - We hypothesized that the increase of retinal capillary blood flow (RCF) to flicker light exposure is impaired in subjects with arterial hypertension. In 146 nondiabetic untreated male subjects with (n=50) or without (n=96) arterial hypertension, RCF was measured before and after flicker light exposure noninvasively and in vivo using scanning laser Doppler flowmetry. In addition, in a subgroup of 28 subjects, the change of RCF to flicker light exposure was again assessed during parallel infusion of nitric oxide synthase inhibitor N-monomethyl L-arginine (L-NMMA). The increase of RCF to flicker light exposure was lower in patients with untreated hypertension compared with normotensive subjects when expressed in absolute terms (7.69+/-54 versus 27.2+/-44 AU; P adjusted=0.013) or percent changes (2.95+/-14 versus 8.33+/-12%; P adjusted=0.023). Systolic (beta= 0.216; P=0.023) but not diastolic blood pressure (beta=-0.117; P=0.243) or mean arterial pressure (beta=-0.178; P=0.073) was negatively related to the percent change of RCF to flicker light exposure, independently of other cardiovascular risk factors. In the subgroup of 28 subjects, the increase of RCF to flicker light exposure was similar at baseline and during parallel infusion of L-NMMA when expressed in absolute terms (20.0+/-51 versus 22.6+/-56 AU; P=0.731) or percent changes (7.12+/-16 versus 8.29+/-18%; P=0.607). The increase of RCF to flicker light exposure is impaired in arterial hypertension. In the subgroup of the total study cohort, nitric oxide was not a major determinant of the increase of RCF to flicker light exposure. PMID- 22777935 TI - Angiotensin II type 2 receptor-mediated inhibition of NaCl absorption is blunted in thick ascending limbs from Dahl salt-sensitive rats. AB - NO reduces NaCl absorption by thick ascending limbs (TALs) by inhibiting the Na/K/2Cl cotransporter (NKCC2). We have shown that NO-induced inhibition of Na transport is reduced in Dahl salt-sensitive rat (SS) TALs. Angiotensin II increases NO production in TALs via angiotensin II type 2 receptor (AT(2)R). It is unknown whether AT(2)Rs regulate TAL NaCl absorption and whether this effect is reduced in SS rats. We hypothesized that AT(2)R activation decreases TAL Na transport via NO, and this effect is blunted in SS rats. In the presence of angiotensin II type 1 receptor antagonist losartan, AT(2)R activation with angiotensin II inhibited NKCC2 activity by 32+/-7% (P<0.03). AT(2)R antagonist PD 123319 abolished the effect of angiotensin II. Activation with the AT(2)R selective agonist CGP42112A (10 nmol/L) decreased NKCC2 activity by 29+/-6% (P<0.03). The effect of CGP42112A on NKCC2 activity was blocked by PD-123319 and by NO synthase inhibitor N(G)-nitro-l-arginine methyl ester. In Dahl salt resistant rat TALs, 1 nmol/L of CGP42112A decreased NKCC2 activity by 23+/-4% (P<0.01). In SS TALs, it had no effect. TAL AT(2)R mRNA did not differ in SS versus salt-resistant rats. We conclude the following: (1) TAL AT(2)R activation decreases Na absorption; (2) this effect is mediated by AT(2)R-induced stimulation of NO; (3) AT(2)R-induced reduction of NKCC2 activity is blunted in SS rats; and (4) defects in AT(2)R/NO signaling rather than decreased AT(2)R expression likely account for the blunted effect in SS TALs. Impaired AT(2)R mediated signaling in TALs could contribute to the Na retention associated with salt-sensitive hypertension. PMID- 22777936 TI - Visit-to-visit blood pressure variability is a strong predictor of cardiovascular events in hemodialysis: insights from FOSIDIAL. AB - Optimal blood pressure (BP) targets are still controversial in end-stage renal disease. Recent data have highlighted shortcomings of the usual BP hypothesis in other patient populations and emphasized the importance of visit-to-visit variability of BP in predicting cardiovascular events. The Fosinopril in Dialysis Study failed to demonstrate the efficacy of 2-year angiotensin-converting enzyme inhibition with fosinopril versus placebo in 397 hemodialysis patients with left ventricular hypertrophy but provided an opportunity to assess the influence of BP variability on cardiovascular events. The primary end point was the occurrence of a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina, stroke, revascularization, hospitalization for heart failure, and resuscitated cardiac arrest. The variations in BP throughout the 17 visits were assessed by within-patient overall variability of systolic, diastolic, and pulse pressures between adjacent readings, by within-patient overall variability of systolic/diastolic/pulse pressures, and the residual of the linear fit. Compared with our previous predictive model of cardiovascular events occurrence based on stroke, peripheral arterial disease, coronary artery disease, diabetes mellitus, left ventricular mass, and age (which exhibited similar coefficients herein), the percentage of explained variance improved by 30.1% (R(2)=0.141-0.183) when adding the coefficient of variation of within-patient overall variability of systolic BP. Usual BP parameters were neither cardiovascular events predictors nor correlated to BP variability. Visit-to-visit BP variability was extremely high in hemodialysis patients compared with other populations and a major determinant of cardiovascular events. Such assessments should be prioritized for testing prevention strategies in end-stage renal disease. PMID- 22777937 TI - Elderly blacks have a blunted sympathetic neural responsiveness but greater pressor response to orthostasis than elderly whites. AB - Neural control of blood pressure (BP) has been reported to differ between young blacks and whites. We hypothesized that elderly blacks have enhanced sympathetic neural responses during orthostasis compared with elderly whites. Muscle sympathetic nerve activity, arm-cuff BP, and heart rate were recorded continuously, and cardiac output, stroke volume, and total peripheral resistance were measured intermittently during supine and 5-minute 60 degrees upright tilt in 10 blacks (65 [SD, 4] years; 4 women) and 20 whites (68 [6] years; 8 women). We found that muscle sympathetic nerve activity burst frequency was similar between blacks and whites in the supine position (44 [10] versus 42 [7] bursts per minute) and during upright tilt (59 [11] versus 60 [9] bursts per minute; P=0.846 for race, P<0.001 for posture, and P=0.622 for interaction). However, upright total muscle sympathetic nerve activity was smaller in blacks than in whites (162 [39] versus 243 [112]%; P=0.003). Systolic BP, heart rate, cardiac output, and stroke volume were not different between groups. Diastolic BP was similar in the supine position, increased in all of the subjects during tilting; upright diastolic BP was greater in blacks than in whites (80 [10] versus 71 [7] mmHg; P=0.008). Total peripheral resistance did not differ between blacks and whites in the supine position or during upright tilt (P=0.354 for race, P<0.001 for posture, P=0.825 for interaction). Thus, elderly blacks have a blunted sympathetic neural responsiveness but enhanced pressor response to orthostasis compared with elderly whites, which may be attributable to an augmented sympathetic vascular transduction and/or nonadrenergic vasoconstrictor mechanisms (ie, angiotensin II or the venoarteriolar response). PMID- 22777939 TI - Is vascular morning blood pressure surge in the elderly resistant to antihypertensives and more risky? PMID- 22777938 TI - Chronic hypoxia during gestation causes epigenetic repression of the estrogen receptor-alpha gene in ovine uterine arteries via heightened promoter methylation. AB - Estrogen receptor-alpha (ERalpha) plays a key role in the adaptation of increased uterine blood flow in pregnancy. Chronic hypoxia is a common stress to maternal cardiovascular homeostasis and causes increased risk of preeclampsia. Studies in pregnant sheep demonstrated that hypoxia during gestation downregulated ERalpha gene expression in uterine arteries. The present study tested the hypothesis that hypoxia causes epigenetic repression of the ERalpha gene in uterine arteries via heightened promoter methylation. Ovine ERalpha promoter of 2035 bp spanning from 2000 to +35 of the transcription start site was cloned. No estrogen or hypoxia inducible factor response elements were found at the promoter. Two transcription factor binding sites, USF(-15) and Sp1(-520), containing CpG dinucleotides were identified, which had significant effects on the promoter activity. The USF element binds transcription factors USF1 and USF2, and the Sp1 element binds Sp1, as well as ERalpha through Sp1. Deletion of the Sp1 site abrogated 17beta estradiol-induced increase in the promoter activity. In normoxic control sheep, CpG methylation at the Sp1 but not the USF site was significantly decreased in uterine arteries of pregnant as compared with nonpregnant animals. In pregnant sheep exposed to long-term high-altitude hypoxia, CpG methylation at both Sp1 and USF sites in uterine arteries was significantly increased. Methylation inhibited transcription factor binding and the promoter activity. The results provide evidence of hypoxia causing heightened promoter methylation and resultant ERalpha gene repression in uterine arteries and suggest new insights of molecular mechanisms linking gestational hypoxia to aberrant uteroplacental circulation and increased risk of preeclampsia. PMID- 22777941 TI - Failure to downregulate the epithelial sodium channel causes salt sensitivity in Hsd11b2 heterozygote mice. AB - In vivo, the enzyme 11beta-hydroxysteroid dehydrogenase type 2 influences ligand access to the mineralocorticoid receptor. Ablation of the encoding gene, HSD11B2, causes the hypertensive syndrome of apparent mineralocorticoid excess. Studies in humans and experimental animals have linked reduced 11beta-hydroxysteroid dehydrogenase type 2 activity and salt sensitivity of blood pressure. In the present study, renal mechanisms underpinning salt sensitivity were investigated in Hsd11b2(+/-) mice fed low-, standard-, and high-sodium diets. In wild-type mice, there was a strong correlation between dietary sodium content and fractional sodium excretion but not blood pressure. High sodium feeding abolished amiloride-sensitive sodium reabsorption, consistent with downregulation of the epithelial sodium channel. In Hsd11b2(+/-) mice, the natriuretic response to increased dietary sodium content was blunted, and epithelial sodium channel activity persisted. High-sodium diet also reduced renal blood flow and increased blood pressure in Hsd11b2(+/-) mice. Aldosterone was modulated by dietary sodium in both genotypes, and salt sensitivity in Hsd11b2(+/-) mice was associated with increased plasma corticosterone levels. Chronic administration of an epithelial sodium channel blocker or a glucocorticoid receptor antagonist prevented salt sensitivity in Hsd11b2(+/-) mice, whereas mineralocorticoid receptor blockade with spironolactone did not. This study shows that reduced 11beta-hydroxysteroid dehydrogenase type 2 causes salt sensitivity of blood pressure because of impaired renal natriuretic capacity. This reflects deregulation of epithelial sodium channels and increased renal vascular resistance. The phenotype is not caused by illicit activation of mineralocorticoid receptors by glucocorticoids but by direct activation of glucocorticoid receptors. PMID- 22777940 TI - Normal IgG downregulates the intracellular superoxide level and attenuates migration and permeability in human aortic endothelial cells isolated from a hypertensive patient. AB - The normal IgG, a circulating antibody, is maintained at a constant level in humans. However, little is known regarding whether normal IgG has effects on the function of vascular endothelial cells. The purpose of this study was to investigate whether IgG affects superoxide (O(2)(.-)) generation and cell permeability in human aortic endothelial cells (HAECs) isolated from a hypertensive patient. The effect of normal human IgG on endothelial cell function was investigated in cultured HAECs isolated from a hypertensive patient who died of stroke. The results demonstrated, for the first time, that normal IgG attenuated the intracellular O(2)(.-) level and decreased cell migration, cell permeability, and stress fiber formation in HAECs. IgG significantly decreased Rac1 activity and NADPH oxidase activity but upregulated Mn superoxide dismutase expression in HAECs, which may contribute to the IgG-induced decrease in O(2)(.-) level. It is noted that AMP-activated protein kinase (AMPK) was activated by IgG, as evidenced by increased phosphorylation of AMPK. Interestingly, inhibition of AMPK by an AMPK inhibitor abolished IgG-induced decreases in Rac1 and NADPH oxidase activities and IgG-induced increases in Mn superoxide dismutase expression, suggesting that AMPK is an important mediator of the IgG-induced regulation of these enzymes. Importantly, inhibition of AMPK activity also prevented the IgG-induced decrease in O(2)(.-) levels, cell migration, cell permeability, and stress fiber formation. Therefore, normal human IgG may protect HAECs via activation of AMPK and subsequent decreases in intracellular O(2)(.-). These findings reveal a previously unidentified role of normal IgG in regulating AMPK and endothelial cell function. PMID- 22777943 TI - Diagnostic value of serum anti-C1q antibodies in patients with lupus nephritis: a meta-analysis. AB - The autoantibodies against C1q (anti-C1q) have been reported in patients with systemic lupus erythematosus (SLE). In the past decade, though there were increasing studies suggesting it is relatively specific in lupus nephritis (LN), its overall diagnostic value in LN has not been evaluated. The meta-analysis was conducted to quantitatively evaluate the diagnostic accuracy of autoantibodies against C1q in patients with LN, and to provide more precise evidence of a correlation between anti-C1q antibodies and activity of LN. We searched Medline, Embase and Cochrane databases and contacted authors if necessary. A total of 25 studies including 2,502 patients with SLE and 1,317 with LN met our inclusion criteria for this meta-analysis. Among all 25 studies, 22 studies were available for comparison between SLE with and without LN, and 9 studies compared anti-C1q between patients with active and inactive LN. Summary receiver operating characteristic (SROC) curve was used to summarize comprehensive test performance. The QUADAS tool was used to assess the quality of the studies. For the diagnosis of LN, the pooled sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of anti-C1q were 0.58 (0.56-0.61, 95% confidence interval [95% CI]), 0.75 (0.72-0.77, 95% CI), 2.60 (2.06-3.28, 95% CI), 0.51 (0.41-0.63, 95% CI), and 6.08 (3.91-9.47, 95% CI) respectively. The area under the SROC curve (AUC) was 0.7941. For comparison between active and inactive LN, the weighted sensitivity, specificity, PLR, NLR and DOR were 0.74 (0.68-0.79, 95% CI), 0.77 (0.71-0.82, 95% CI), 2.91 (1.83-4.65, 95% CI), 0.33 (0.19-0.56, 95% CI), and 10.56 (4.56-24.46, 95% CI) respectively. The AUC was 0.8378. In conclusion, this meta-analysis indicates that anti-C1q antibodies have relatively fair sensitivity and specificity in the diagnosis of LN, suggesting that the presence of anti-C1q antibodies may be a valuable adjunct for predicting LN and assessing renal activity. PMID- 22777942 TI - Role of transmembrane semaphorin Sema6A in oligodendrocyte differentiation and myelination. AB - Myelination is regulated by extracellular proteins, which control interactions between oligodendrocytes and axons. Semaphorins are repulsive axon guidance molecules, which control the migration of oligodendrocyte precursors during normal development and possibly in demyelinating diseases. We show here that the transmembrane semaphorin 6A (Sema6A) is highly expressed by myelinating oligodendrocytes in the postnatal mouse brain. In adult mice, Sema6A expression is upregulated in demyelinating lesions in cuprizone-treated mice. The analysis of the optic nerve and anterior commissure of Sema6A-deficient mice revealed a marked delay of oligodendrocyte differentiation. Accordingly, the development of the nodes of Ranvier is also transiently delayed. We also observed an arrest in the in vitro differentiation of purified oligodendrocytes lacking Sema6A, with a reduction of the expression level of Myelin Basic Protein. Their morphology is also abnormal, with less complex and ramified processes than wild-type oligodendrocytes. In myelinating co-cultures of dorsal root ganglion neurons and purified oligodendrocytes we found that myelination is perturbed in absence of Sema6A. These results suggest that Sema6A might have a role in myelination by controlling oligodendrocyte differentiation. PMID- 22777944 TI - Efficacy of various naturally occurring caffeic acid derivatives in preventing post-harvest protein losses in forages. AB - BACKGROUND: In red clover, oxidation of endogenous o-diphenols by polyphenol oxidase (PPO) inhibits post-harvest proteolyis. This system is transferable to alfalfa by providing PPO (via a transgene) and o-diphenol PPO substrates (via exogenous application). To exploit the PPO system for protein protection, it would be advantageous to produce PPO substrates in alfalfa, which lacks them. We assessed the extent of PPO-mediated proteolytic inhibition by phenolic compounds, especially those whose biosynthesis could be engineered into alfalfa. RESULTS: Tested compounds included o-diphenols (caffeic acid, phaselic acid, chlorogenic acid, clovamide) and monophenols (p-coumaric acid, p-coumaroyl-malic acid). In the presence of PPO, 2 mmol o-diphenol g-1 protein reduced 24 h proteolysis 68 87% (P < 0.001) and as little as 0.25 mmol g-1 protein still decreased 24 h proteolysis 43-60% (P < 0.001). At high concentrations, clovamide inhibited 24 h proteolysis 50% (P < 0.001) in the absence of PPO, likely due to non-PPO oxidation. Monophenol p-coumaric acid did not inhibit 24 h proteolyis, although high levels of its malate ester did exhibit PPO- and oxygen-independent inhibition (37%, P < 0.001). CONCLUSIONS: For PPO-mediated proteolytic inhibition, pathways for both phaselic acid and chlorogenic acid may be good targets for engineering into alfalfa. Clovamide may be useful for inhibiting proteolysis without PPO. PMID- 22777947 TI - Reversible generalized dystonia and encephalopathy from thiamine transporter 2 deficiency. AB - BACKGROUND: Thiamine transporter-2 deficiency, a condition resulting from mutations in the SLC19A3 gene, has been described in patients with subacute dystonia and striatal necrosis. The condition responds extremely well to treatment with biotin and has thus been named biotin-responsive basal ganglia disease. Recently, this deficiency has also been related to Wernicke's-like encephalopathy and atypical infantile spasms, showing heterogeneous responses to biotin and/or thiamine. METHODS: Two Spanish siblings with a biotin-responsive basal ganglia disease phenotype and mutations in SLC19A3 presented with acute episodes of generalized dystonia, rigidity, and symmetrical lesions involving the striatum, midline nuclei of the thalami, and the cortex of cerebral hemispheres as shown by magnetic resonance imaging. RESULTS: The clinical features resolved rapidly after thiamine administration. CONCLUSIONS: Despite the rarity of thiamine transporter-2 deficiency, it should be suspected in patients with acute dystonia and basal ganglia injury, as thiamine can halt disease evolution and prevent further episodes. (c) 2012 Movement Disorder Society. PMID- 22777948 TI - A carbon nanotube toxicity paradigm driven by mast cells and the IL-33/ST2 axis. AB - Concern about the use of nanomaterials has increased significantly in recent years due to potentially hazardous impacts on human health. Mast cells are critical for innate and adaptive immune responses, often modulating allergic and pathogenic conditions. Mast cells are well known to act in response to danger signals through a variety of receptors and pathways including IL-33 and the IL-1 like receptor ST2. Here, the involvement of mast cells and the IL-33/ST2 axis in pulmonary and cardiovascular responses to multi-walled carbon nanotube (MWCNT) exposure are examined. Toxicological effects of MWCNTs are observed only in mice with a sufficient population of mast cells and are not observed when mast cells are absent or incapable of responding to IL-33. Our findings establish for the first time that mast cells and the IL-33/ST2 axis orchestrates adverse pulmonary and cardiovascular responses to an engineered nanomaterial, giving insight into a previously unknown mechanism of toxicity. This novel mechanism of toxicity could be used for assessing the safety of engineered nanomaterials and provides a realistic therapeutic target for potential nanoparticle induced toxicities. PMID- 22777949 TI - In search of an osteoblast cell model for in vitro research. AB - The process of bone formation, remodelling and healing involves a coordinated action of various cell types. Advances in understanding the biology of osteoblast cells during these processes have been enabled through the use of various in vitro culture models from different origins. In an era of intensive bone tissue engineering research, these cell models are more and more often applied due to limited availability of primary human osteoblast cells. While they are a helpful tool in developing novel therapies or biomaterials; concerns arise regarding their phenotypic state and differences in relation to primary human osteoblast cells. In this review we discuss the osteoblastic development of some of the available cell models; such as primary human, rat, mouse, bovine, ovine and rabbit osteoblast cells; as well as MC3T3-E1, MG-63 and SaOs-2 cell lines, together with their advantages and disadvantages. Through this, we provide suggestions on the selection of the appropriate and most relevant osteoblast model for in vitro studies, with specific emphasis on cell-material based studies. PMID- 22777950 TI - Sustained and promoter dependent bone morphogenetic protein expression by rat mesenchymal stem cells after BMP-2 transgene electrotransfer. AB - Transplantation of mesenchymal stem cells (MSCs) with electrotransferred bone morphogenetic protein-2 (BMP-2) transgene is an attractive therapeutic modality for the treatment of large bone defects: it provides both stem cells with the ability to form bone and an effective bone inducer while avoiding viral gene transfer. The objective of the present study was to determine the influence of the promoter driving the human BMP-2 gene on the level and duration of BMP-2 expression after transgene electrotransfer into rat MSCs. Cytomegalovirus, elongation factor-1alpha, glyceraldehyde 3-phosphate dehydrogenase, and beta actin promoters resulted in a BMP-2 secretion rate increase of 11-, 78-, 66- and 36-fold over respective controls, respectively. In contrast, the osteocalcin promoter had predictable weak activity in undifferentiated MSCs but induced the strongest BMP-2 secretion rates in osteoblastically-differentiated MSCs. Regardless of the promoter driving the transgene, a plateau of maximal BMP-2 secretion persisted for at least 21 d after the hBMP-2 gene electrotransfer. The present study demonstrates the feasibility of gene electrotransfer for efficient BMP-2 transgene delivery into MSCs and for a three-week sustained BMP-2 expression. It also provides the first in vitro evidence for a safe alternative to viral methods that permit efficient BMP-2 gene delivery and expression in MSCs but raise safety concerns that are critical when considering clinical applications. PMID- 22777951 TI - Contribution of postero-anterior cephalometry in obstructive sleep apnea. AB - OBJECTIVES/HYPOTHESIS: Lateral cephalometry has been widely used to characterize facial and maxillary morphology in obstructive sleep apnea (OSA) patients. It is a useful tool to assess orthodontic and maxillofacial procedures, but transverse dimensions of the airway (e.g., nasal framework) have not been well described yet by cephalometry. We explored whether postero-anterior cephalometry could refine the analysis of the facial morphology, with a special attention paid to nasal morphology. We validated cephalometric measurements relevant to the diagnosis of OSA. STUDY DESIGN: Controlled study. METHODS: We explored postero-anterior and lateral cephalometric bony structures in OSA patients and in control subjects to determine which were predictive of an association with OSA. Healthy volunteers paired for age and sex to OSA patients underwent polysomnography and cephalometry. Data were analyzed by Shapiro-Wilk, Fisher, Wilcoxon, and paired t tests where appropriate. RESULTS: Nasal fossae and maxillary bone proportions were positively and independently associated with the absence of OSA. Measurements of maxillary width, nasal fossae angle, and anterior skull base contributed to the characterization of OSA patients. CONCLUSIONS: Postero anterior cephalometry is an easy, rapid, informative, and reliable technique, which is complementary to the lateral cephalometry in the assessment of OSA patients. Our study may also suggest the negative impact of the nasal resistance on the upper airway resistance in sleep disorders. PMID- 22777952 TI - Quality of life and sexual functioning in young women with early-stage breast cancer 1 year after lumpectomy. AB - BACKGROUND: The breast cancer (BC) and its treatment (mastectomy, radiotherapy, and chemotherapy) have considerable psychosexual impacts on women's life. This study evaluated sexual functioning, quality of life, and self-esteem in young women with early-stage BC. METHODS: A total of 186 women with stage I or II BC and 204 age-matched controls aged 25-45 years were recruited. To be eligible, patients had to be disease-free and sexually active. They also had to have undergone lumpectomy at least 1 year previously and have completed chemotherapy and/or radiotherapy. Subjects completed Female Sexual Function Index, Short Form 36 Health Survey, and Rosenberg Self-Esteem questionnaire. Serum sex hormones were also measured in all subjects. RESULTS: Of BC patients, 57% experienced lubrication disorder followed by satisfaction disorder in 53.8%, desire disorder in 42.5%, and arousal disorder in 37.0% (all patients vs. healthy controls <0.01). Hormone-treated patients were more likely to report sexual dysfunctions (p = 0.006). The radiotherapy + chemotherapy + hormone therapy was associated with an about sixfold increased risk of lubrication and satisfaction disorders (adjusted odds ratios = 6.4, 95%CI = 4.6-12.6, and adjusted odds ratios = 5.7, 95%CI = 3.4-11.4, respectively). Cancer patients had lower scores for all components of the Short Form-36 Health Survey, except for pain. Levels of self esteem did not differ significantly between the two groups. CONCLUSIONS: Young lumpectomized BC women reported a marked impairment in sexual functioning and quality of life. PMID- 22777953 TI - Copper catalyst activation driven by photoinduced electron transfer: a prototype photolatent click catalyst. AB - PET cat. While the copper(II) tren ketoprofenate precatalyst 1 (see picture) is inactive at room temperature in methanol, it is quantitatively and rapidly reduced to its cuprous state upon light irradiation to provide a highly reactive click catalyst. By simply introducing air into the reaction medium the catalysis can be switched off and then switched on again by bubbling argon followed by irradiation. PMID- 22777955 TI - The role of anxiety sensitivity, behavioral inhibition, and cognitive biases in anxiety symptoms: structural equation modeling of direct and indirect pathways. AB - OBJECTIVE(S): Limited research has examined how temperamental (i.e., behavioral inhibition, anxiety sensitivity) and cognitive (i.e., interpretive and judgment biases) risks for the development anxiety covary to influence anxiety symptoms. Thus, the present study aimed to advance understanding of the direct and indirect links between anxiety sensitivity, behavioral inhibition, and interpretive biases, and judgment biases (in the form of perceived control) to anxiety outcomes (i.e., worry and trait anxiety symptoms). METHOD: 842 emerging adults (mean = 18.75 years, standard deviation = 1.05; age range = 18-24; 70% women) recruited from a university in the northeast participated in this study. Participants completed a battery of self-report measures assessing risk factors and anxiety outcomes of interest. RESULTS: Structural equation modeling revealed anxiety sensitivity and behavioral inhibition were directly linked with anxiety outcomes. Anxiety sensitivity and behavioral inhibition were also indirectly linked with anxiety outcomes through interpretive and judgment biases. The hypothesized model was partially invariant across high-risk and low-risk groups for anxiety disorders. CONCLUSIONS: Results of this study provide preliminary support for theoretical models hypothesizing a developmental progression from temperamental to cognitive risks and culminating in the expression of anxiety symptoms. Limitations and clinical implications of this research are discussed. PMID- 22777954 TI - Genetically targetable and color-switching fluorescent probe. AB - Color bind: We have developed a probe TMR-para-MG that switches its fluorescence emission upon binding to a fluorogen-activating protein (FAP). In cells that express FAP, this dye labels target sites in one color and mitochondria in another color, thus it might be a suitable tool for monitoring changes in mitochondrial membrane potential. PMID- 22777956 TI - Efficacy of transnasal endoscopic resection for malignant anterior skull-base tumors. AB - BACKGROUND: Craniofacial resection (CFR) has been the standard of care for malignant tumors of the anterior skull base (ASB). However, during the past 2 decades, transnasal endoscopic resection (TER) has gained significant popularity. The purpose of this study is to compare CFR and TER with respect to perioperative and oncologic outcomes. METHODS: Retrospective analysis at a tertiary care medical center of 82 consecutive patients undergoing resection of tumors of the ASB between 1997 and 2011. RESULTS: Thirty-four patients underwent TER, while 48 patients underwent CFR. There was no statistical difference in major complications between the two groups (p = 0.29). However, TER patients had shorter operating room times (284 minutes for TER, 620 minutes for CFR; p < 0.001), lower intraoperative blood loss (675 mL for TER, 1000 mL for CFR; p = 0.005), shorter intensive care unit (ICU) stays (0 days for TER, 3 days for CFR; p < 0.001), and shorter hospital stays (4.5 days for TER; 7 days for CFR; p < 0.001). There were no differences for the rates of en bloc resection, negative margins, or disease-specific mortality. Subanalysis yielded a median follow-up of 5 years postoperatively. There were no differences in disease-specific mortality or recurrences in this group. CONCLUSION: Patients undergoing TER for tumors of the ASB are more likely to leave the ICU and the hospital earlier than their CFR counterparts. Furthermore, for carefully selected patients undergoing TER, excellent oncologic outcomes with survival and recurrence rates similar to patients undergoing CFR may be achieved. Comparison of oncologic outcomes, however, may be limited by discrepancy in histologic grade and clinical stage between the two groups. Nonetheless, TER seems to be an excellent alternative to CFR in appropriately selected patients. PMID- 22777957 TI - Local production of serum amyloid a is implicated in the induction of macrophage chemoattractants in Schwann cells during wallerian degeneration of peripheral nerves. AB - The elevation of serum levels of serum amyloid A (SAA) has been regarded as an acute reactive response following inflammation and various types of injuries. SAA from the liver and extrahepatic tissues plays an immunomodulatory role in a variety of pathophysiological conditions. Inflammatory cytokines in the peripheral nerves have been implicated in the Wallerian degeneration of peripheral nerves after injury and in certain types of inflammatory neuropathies. In the present study, we found that a sciatic nerve axotomy could induce an increase of SAA1 and SAA3 mRNA expression in sciatic nerves. Immunohistochemical staining showed that Schwann cells are the primary sources of SAA production after nerve injury. In addition, interleukin-6-null mice, but not tumor necrosis factor-alpha-null mice showed a defect in the production of SAA1 in sciatic nerve following injury. Dexamethasone treatment enhanced the expression and secretion of SAA1 and SAA3 in sciatic nerve explants cultures, suggesting that interleukin 6 and corticosteroids might be major regulators for SAA production in Schwann cells following injury. Moreover, the stimulation of Schwann cells with SAA1 elicited the production of the macrophage chemoattractants, Ccl2 and Ccl3, in part through a G-protein coupled receptor. Our findings suggest that locally produced SAA might play an important role in Wallerian degeneration after peripheral nerve injury. PMID- 22777958 TI - Cyclosquaramides as kinase inhibitors with anticancer activity. AB - We report the synthesis and biological evaluation of a new series of oligosquaramide-based macrocycles as anticancer agents. Compound 7, considered as representative of this series, exhibited significant antiproliferative activity against the NCI-60 human tumor cell line panel, with IC(50) values ranging from 1 to 10 MUM. The results show that sensitivity to cyclosquaramides is clearly dependent on cell type, underscoring a degree of biological selectivity. The observed antiproliferative effects appear to be related to deregulation of protein phosphorylation, as compounds 7 and 8 are effective inhibitors of several important kinases such as ABL1, CDK4, CHK1, PKC, c-MET, and FGFR, among others. The corresponding acyclic oligosquaramides and smaller cyclosquaramides did not show antitumor activity, suggesting that a macrocyclic structure with minimal molecular size plays a key role in the observed antitumor activity. PMID- 22777959 TI - CD31 angiogenesis and combined expression of HIF-1alpha and HIF-2alpha are prognostic in primary clear-cell renal cell carcinoma (CC-RCC), but HIFalpha transcriptional products are not: implications for antiangiogenic trials and HIFalpha biomarker studies in primary CC-RCC. AB - Hypoxia-inducible factors, HIF-1alpha and HIF-2alpha, are expressed in the majority of clear-cell renal cell carcinoma (CC-RCC). In vitro, HIFalpha isoforms regulate a differential set of genes, and their effects in vivo within CC-RCC tumours may affect outcome. The role of angiogenesis and HIFalpha transcriptional products, including those involved in cell metabolism and morphological dedifferentiation have not been extensively investigated and might have relevance to the development of antiangiogenic or anti-HIFalpha trials in primary CC-RCC, either before or after radical nephrectomy. We analysed 168 consecutive clear cell renal tumours from 1983 to 1999 within tissue microarrays and assessed expression of HIF-1alpha and HIF-2alpha together with the protein expression of seven of their target genes (BNIP3, CA9, Cyclin D1, GLUT-1, LDH5, Oct-4 and VEGF). The expression of these factors was compared with patient overall survival and CD31 angiogenesis. We found that HIFalpha antigenicity deteriorated with the age of the paraffin block (P < 0.0001) and in tumours from 1983 to 1992 was deemed not to be reliable. Similar findings were found in aged archival osteosarcoma samples. This might have important implications for retrospective biomarker studies that rely on archival tissue material. HIF-1alpha(HIGH)/HIF 2alpha(LOW) tumours had a worse overall survival compared with HIF 1alpha(LOW)/HIF-2alpha(LOW) tumours (P = 0.04). Surprisingly, on multivariate analysis, high levels of CD31(+) angiogenesis was shown to be an independent prognostic marker of increased overall survival (P = 0.003). We propose that better differentiation of vascular endothelium may be a reflection of a greater production of vessel stabilization factors versus pro-angiogenic factors, and therefore a less aggressive phenotype. PMID- 22777960 TI - Deletion diagnostics for alternating logistic regressions. AB - Deletion diagnostics are introduced for the regression analysis of clustered binary outcomes estimated with alternating logistic regressions, an implementation of generalized estimating equations (GEE) that estimates regression coefficients in a marginal mean model and in a model for the intracluster association given by the log odds ratio. The diagnostics are developed within an estimating equations framework that recasts the estimating functions for association parameters based upon conditional residuals into equivalent functions based upon marginal residuals. Extensions of earlier work on GEE diagnostics follow directly, including computational formulae for one-step deletion diagnostics that measure the influence of a cluster of observations on the estimated regression parameters and on the overall marginal mean or association model fit. The diagnostic formulae are evaluated with simulations studies and with an application concerning an assessment of factors associated with health maintenance visits in primary care medical practices. The application and the simulations demonstrate that the proposed cluster-deletion diagnostics for alternating logistic regressions are good approximations of their exact fully iterated counterparts. PMID- 22777961 TI - Expressions of TGF-beta1 and MMP-9 in a guinea pig model of tympanosclerosis: possible role in the pathogenesis of this disorder. AB - OBJECTIVES/HYPOTHESIS: The present study was performed to investigate the expressions of transforming growth factor beta1 (TGF-beta1) and matrix metalloproteinase-9 (MMP-9) in an experimental model of tympanosclerosis and their possible roles in the formation of this disorder. STUDY DESIGN: A prospective experimental animal study. METHODS: Seventy guinea pigs were used in this study, of which 10 were chosen to serve as controls, and the other 60 were used in the tympanosclerosis group by inoculation of type-3 Streptococcus pneumoniae microorganisms. The experimental animals were further divided into six subgroups on the basis of six time points. Otomicroscopy was employed to observe the development of myringosclerosis. Hematoxylin-eosin and von Kossa staining were performed to determine the morphological changes and calcium depositions. The expressions of TGF-beta1 and MMP-9 were assessed by Western blot and immunohistochemistry. RESULTS: Slight sclerotic changes in tympanic membrane were found at week 2, and extensive myringosclerosis was observed at week 6. Hyalinization and calcification in the tympanic membrane and middle ear mucous membrane were clearly visible at week 6. Expression of TGF-beta1 was significantly increased with the development of tympanosclerosis. Expression of MMP-9 was increased from week 1 to week 4, and then declined at week 6. These two cytokines were both distributed in the cytoplasm of fibroblast cells and inflammatory cells, which were widely distributed in the tympanic membrane and middle ear mucosa at week 6. CONCLUSIONS: Our data indicate that, for the first time, the alteration in expressions of TGF-beta1 and MMP-9 were involved in the formation of tympanosclerosis, which may represent an important mechanism underlying the pathogenesis of tympanosclerosis. PMID- 22777963 TI - Association between tamoxifen treatment and diabetes: a population-based study. PMID- 22777964 TI - High frequency of Parkin exon rearrangements in Mexican-mestizo patients with early-onset Parkinson's disease. AB - BACKGROUND: Parkin mutations in patients with early-onset Parkinson's disease (EOPD) are estimated to occur in 49% of familial cases and 18% of sporadic cases. METHODS: We analyzed the entire sequence-coding region and dosage mutations of parkin in 63 Mexican-mestizo EOPD patients and 120 controls. RESULTS: Parkin mutations were present in 34 patients (54.0%). Exon rearrangements, predominantly spanning exons 9 and 12 (31.7% and 19.0%, respectively) were present in 32 patients, with 17.5% carrying simple heterozygous and 25.4% carrying compound heterozygous parkin mutations. CONCLUSIONS: A higher frequency of parkin exon rearrangements than of sequence mutations was observed. Patients with parkin exons 9 and 12 rearrangements showed a later age at onset than did cases with other regions affected (40.3 +/- 4.5 vs 30.1 +/- 8.8; P = .005), suggesting a mutational hot spot in the etiology of Mexican-mestizo patients with EOPD. To our knowledge, this study represents the largest sampling of Mexican-mestizo patients with EOPD cases for which parkin sequence and dosage alterations were analyzed. . PMID- 22777965 TI - Rare Earth metal-mediated group transfer polymerization of vinylphosphonates. AB - Recent studies have shown that poly(vinylphosphonate)s are readily accessible by rare earth metal-mediated group transfer polymerization (GTP). This article highlights the progress in this new field and advantages of GTP in comparison to classical anionic and radical polymerization approaches. Late lanthanide metallocenes proved to be efficient initiators and highly active catalysts for vinylphosphonate polymerization yielding polymers of precise molecular weight and low polydispersity. Using this method, our group has developed a surface initiated GTP to prepare poly(vinylphosphonate) brushes. In combination with different ester cleavage strategies, rare earth metal-mediated GTP is an efficient way to create well-defined high-molecular-weight poly(vinylphosphonic acid). PMID- 22777966 TI - Electrophoretic build-up of alternately multilayered films and micropatterns based on graphene sheets and nanoparticles and their applications in flexible supercapacitors. AB - Graphene nanosheets and metal nanoparticles (NPs) have been used as nano-building blocks for assembly into macroscale hybrid structures with promising performance in electrical devices. However, in most graphene and metal NP hybrid structures, the graphene sheets and metal NPs (e.g., AuNPs) do not enable control of the reaction process, orientation of building blocks, and organization at the nanoscale. Here, an electrophoretic layer-by-layer assembly for constructing multilayered reduced graphene oxide (RGO)/AuNP films and lateral micropatterns is presented. This assembly method allows easy control of the nano-architecture of building blocks along the normal direction of the film, including the number and thickness of RGO and AuNP layers, in addition to control of the lateral orientation of the resultant multilayered structures. Conductivity of multilayered RGO/AuNP hybrid nano-architecture shows great improvement caused by a bridging effect of the AuNPs along the out-of-plane direction between the upper and lower RGO layers. The results clearly show the potential of electrophoretic build-up in the fabrication of graphene-based alternately multilayered films and patterns. Finally, flexible supercapacitors based on multilayered RGO/AuNP hybrid films are fabricated, and excellent performance, such as high energy and power densities, are achieved. PMID- 22777967 TI - Too sick. PMID- 22777968 TI - Predicting our future: lessons from Winnie-the-Pooh. PMID- 22777969 TI - When the self is contested ground. PMID- 22777970 TI - Reality checks. PMID- 22777971 TI - America's drug problem. PMID- 22777972 TI - The disasters of March 11th. PMID- 22777973 TI - Comfort care as denial of personhood. PMID- 22777974 TI - Reflections from a troubled stream: Giubilini and Minerva on "after-birth abortion". PMID- 22777975 TI - Child safety, absolute risk, and the prevention paradox. PMID- 22777976 TI - The ethics of vaginal birth after cesarean. PMID- 22777977 TI - Prenatal whole genome sequencing: just because we can, should we? PMID- 22777978 TI - Who is "too sick to benefit"? PMID- 22777980 TI - Scholarly discussion of infanticide? PMID- 22777981 TI - Seeking the unseen. PMID- 22777982 TI - Post-traumatic stress symptoms among mothers of children with leukemia undergoing treatment: a longitudinal study. AB - OBJECTIVE: To assess post-traumatic stress symptoms (PTSS) in mothers of children over 2 years of leukemia treatment, to identify possible early family and child predictors of this symptomatology and to indicate the temporal trajectory of PTSS. METHODS: Participants were 76 Italian mothers (mean age = 37.30 years; SD = 6.07) of children receiving treatment for acute lymphoblastic (n = 69) or myeloid (n = 7) leukemia. Mothers had 12.05 years of education (SD = 3.87), and their incomes were average (52.1%), high (26%) and low (21.9%) for Italian norms, never in poverty. The pediatric patients with leukemia were equally distributed by gender with their mean age of 7.10 years (SD = 4.18). Post-traumatic stress symptoms were measured by a 17-item checklist. Scales assessing anxiety, depression, physical (Brief Symptom Inventory 18) and cognitive functioning (Problem Scale), and life evaluation were also used. There were five assessment points: 1 week (T1), 1 month (T2), 6 months (T3), 12 months (T4) and 24 months post-diagnosis (T5). RESULTS: The main results indicated moderate presence of clinical PTSS (>=9 symptoms: 24% at T2, 18% at T3, 16% at T4 and 19% at T5) that remained stable across time points, whereas Brief Symptom Inventory 18 Global score decreased and life evaluation improved. A series of hierarchical regression models identified cognitive functioning early after the diagnosis as the best predictive factor of PTSS across time points. CONCLUSION: Specific psychological interventions could be devised for mothers at risk for short and long-term PTSS just after the diagnosis. PMID- 22777983 TI - Modified 6-aza uridines: highly emissive pH-sensitive fluorescent nucleosides. AB - Optimized facile syntheses and highly desirable spectroscopic properties of two isomorphic fluorescent pyrimidines, comprising a 1,2,4-triazine motif conjugated to a thiophene (1 a) or a furan (1 b), are described. Although structurally related to their 5-modified uridine counterparts, these modified 6-aza-uridines reveal dramatically improved fluorescence properties and a remarkable sensitivity to polarity and pH changes. The thiophene derivative 1 a has an absorption maximum around 335 nm, which upon excitation yields visible emission with a polarity-sensitive maximum and fluorescence quantum yield ranging from 415 nm (Phi=0.8) to 455 nm (Phi=0.2) in dioxane and water, respectively. Nucleoside 1 a also displays susceptibility to acidity. Correlating emission intensity and solution pH yields a pK(a) value of 6.7-6.9, reasonably close to physiological pH values. The results illustrate that highly sought-after fluorescence features (brightness and responsiveness) are not necessarily the trait of large fluorophores alone, but can be observed with probes that meet stringent isomorphic design criteria. PMID- 22777984 TI - Enantiomeric recognition of racemic 4-aryl-1,4-dihydropyridine derivatives via chiralpak AD-H stationary phases. AB - The chromatographic chiral resolution of two new series of racemic 4-substituted 1,4-dihydropyridine derivatives was studied on a commercial Chiralpak AD-H column. Analytes without 5,5-dimethyl substituents (1-15) are more efficiently resolved than analytes with 5,5-dimethyl groups (16-30). The AD-H column discriminated between enantiomers through both hydrogen bonding attractions and pi-pi interactions. This interpretation is in accord with plots of the logarithm of separation factors, log(alpha), versus sigma (Hammett-Swain substituent parameter) and sigma(+) (Brown substituent constant) plots. By elucidating the effects of the remote substituents on these chiral separations, it was shown that the influence of pi-pi interaction forces increase when steric bulk effects act to decrease the hydrogen bonding attractive forces on the AD-H column. PMID- 22777985 TI - Angioedema associated with the use of angiotensin-converting enzyme inhibitor. PMID- 22777986 TI - Mental health impact of detention and temporary status for refugee claimants under Bill C-31. PMID- 22777989 TI - Health assessments urged for federal laws and regulations. PMID- 22777988 TI - Visibility of the urethral meatus and risk of urinary tract infections in uncircumcised boys. AB - BACKGROUND: Uncircumcised boys are at higher risk for urinary tract infections than circumcised boys. Whether this risk varies with the visibility of the urethral meatus is not known. Our aim was to determine whether there is a hierarchy of risk among uncircumcised boys whose urethral meatuses are visible to differing degrees. METHODS: We conducted a prospective cross-sectional study in one pediatric emergency department. We screened 440 circumcised and uncircumcised boys. Of these, 393 boys who were not toilet trained and for whom the treating physician had requested a catheter urine culture were included in our analysis. At the time of catheter insertion, a nurse characterized the visibility of the urethral meatus (phimosis) using a 3-point scale (completely visible, partially visible or nonvisible). Our primary outcome was urinary tract infection, and our primary exposure variable was the degree of phimosis: completely visible versus partially or nonvisible urethral meatus. RESULTS: Cultures grew from urine samples from 30.0% of uncircumcised boys with a completely visible meatus, and from 23.8% of those with a partially or nonvisible meatus (p = 0.4). The unadjusted odds ratio (OR) for culture growth was 0.73 (95% confidence interval [CI] 0.35-1.52), and the adjusted OR was 0.41 (95% CI 0.17-0.95). Of the boys who were circumcised, 4.8% had urinary tract infections, which was significantly lower than the rate among uncircumcised boys with a completely visible urethral meatus (unadjusted OR 0.12 [95% CI 0.04-0.39], adjusted OR 0.07 [95% CI 0.02 0.26]). INTERPRETATION: We did not see variation in the risk of urinary tract infection with the visibility of the urethral meatus among uncircumcised boys. Compared with circumcised boys, we saw a higher risk of urinary tract infection in uncircumcised boys, irrespective of urethral visibility. PMID- 22777990 TI - Nodding disease confounds clinicians. PMID- 22777992 TI - Professionalism: social media outreach. PMID- 22777991 TI - Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. AB - BACKGROUND: The true benefit of iron supplementation for nonanemic menstruating women with fatigue is unknown. We studied the effect of oral iron therapy on fatigue and quality of life, as well as on hemoglobin, ferritin and soluble transferrin receptor levels, in nonanemic iron-deficient women with unexplained fatigue. METHODS: We performed a multicentre, parallel, randomized controlled, closed-label, observer-blinded trial. We recruited from the practices of 44 primary care physicians in France from March to July 2006. We randomly assigned 198 women aged 18-53 years who complained of fatigue and who had a ferritin level of less than 50 ug/L and hemoglobin greater than 12.0 g/dL to receive either oral ferrous sulfate (80 mg of elemental iron daily; n=102) or placebo (n=96) for 12 weeks. The primary outcome was fatigue as measured on the Current and Past Psychological Scale. Biological markers were measured at 6 and 12 weeks. RESULTS: The mean score on the Current and Past Psychological Scale for fatigue decreased by 47.7% in the iron group and by 28.8% in the placebo group (difference -18.9%, 95% CI -34.5 to -3.2; p=0.02), but there were no significant effects on quality of life (p=0.2), depression (p=0.97) or anxiety (p=0.5). Compared with placebo, iron supplementation increased hemoglobin (0.32 g/dL; p=0.002) and ferritin (11.4 MUg/L; p<0.001) and decreased soluble transferrin receptor (-0.54 mg/L; p<0.001) at 12 weeks. INTERPRETATION: Iron supplementation should be considered for women with unexplained fatigue who have ferritin levels below 50 MUg/L. We suggest assessing the efficiency using blood markers after six weeks of treatment. Trial registration no. EudraCT 2006-000478-56. PMID- 22777993 TI - A 69-year-old man with a painful vesicular rash. PMID- 22777995 TI - Intrinsically disordered p53 and its complexes populate compact conformations in the gas phase. AB - Spontaneous shrinking: the intrinsically disordered tumor suppressor protein p53 was analyzed by using a combination of ion mobility mass spectrometry and molecular dynamics simulations. Structured p53 subdomains retain their overall topology upon transfer into the gas phase. When intrinsically disordered segments are introduced into the protein sequence, however, the complex spontaneously collapses in the gas phase to a compact conformation. PMID- 22777994 TI - Glycoprotein 96 perpetuates the persistent inflammation of rheumatoid arthritis. AB - OBJECTIVE: The mechanisms that contribute to the persistent activation of macrophages in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to determine the contribution of endogenous gp96 in Toll-like receptor (TLR)-mediated macrophage activation in RA. METHODS: RA synovial fluid was used to activate macrophages and HEK-TLR-2 and HEK-TLR-4 cells. Neutralizing antibodies to TLR-2, TLR-4, and gp96 were used to inhibit activation. RA synovial fluid macrophages were isolated by CD14 negative selection. Cell activation was measured by the expression of tumor necrosis factor alpha (TNFalpha) or interleukin-8 messenger RNA. Arthritis was induced in mice by K/BxN serum transfer. The expression of gp96 was determined by immunoblot analysis, enzyme linked immunosorbent assay, and immunohistochemistry. Arthritis was treated with neutralizing anti-gp96 antiserum or control serum. RESULTS: RA synovial fluid induced the activation of macrophages and HEK-TLR-2 and HEK-TLR-4 cells. RA synovial fluid-induced macrophage and HEK-TLR-2 activation was suppressed by neutralizing anti-gp96 antibodies only in the presence of high (>800 ng/ml) rather than low (<400 ng/ml) concentrations of gp96. Neutralization of RA synovial fluid macrophage cell surface gp96 inhibited the constitutive expression of TNFalpha. Supporting the role of gp96 in RA, joint tissue gp96 expression was induced in mice with the K/BxN serum-induced arthritis, and neutralizing antibodies to gp96 ameliorated joint inflammation, as determined by clinical and histologic examination. CONCLUSION: These observations support the notion that gp96 plays a role as an endogenous TLR-2 ligand in RA and identify the TLR-2 pathway as a therapeutic target. PMID- 22777996 TI - Chemical contamination during the preparation of cytotoxics: validation protocol for operators in hospital pharmacies. AB - BACKGROUND AND OBJECTIVES: The chemical contamination during the preparation of cytotoxics remains a serious problem in hospital pharmacies and the operators could contribute to this risk during their manipulations. A validation protocol was developed using a non-toxic, highly detectable tracer, quinine dihydrochloride. METHOD: Further, a method for a high recovery extraction and quantification of this marker, and a protocol covering the critical operations of cytotoxic preparation, was developed and validated. Various devices were used to fill the syringes and perfusion bags. All the filled containers and used materials were collected at the end of the protocol and the tracer was extracted in water. The contaminated water was analyzed by fluorimetry. The number of spots on the working pads was counted under ultraviolet light. During a total of 28 sessions, the procedure was applied by 20 different operators. RESULTS: The mean cumulated quantities of contamination were 6.2 uL (0.6-23.8) and >10 spots (0 20), which was considered as high. No correlation was observed between the contamination rate and the operator's experience. CONCLUSION: This validation protocol facilitates controlling the operators' working 'cleanliness' and helps to improve the initial and continuing training. This simple test presents an effective answer for the important issue of the chemical safety of operators. PMID- 22777997 TI - Bevacizumab in lung cancer: lackluster performance and unjustified expense? AB - A recent retrospective analysis of a large cohort of patients aged 65 and older with advanced non-small cell lung cancer failed to demonstrate any improvement in survival with the addition of bevacizumab to the platinum doublet in the first line therapy. A few points have to be made: 1) a vast majority of patients with lung cancer are 65 and older; 2) important including fatal toxicity can occur with the use of bevacizumab; and 3) costs of bevacizumab are significant. Integrating the conclusions of this study into clinical practice and further analysis of underlying physical, psychosocial, and economic hurdles of bevacizumab use in lung cancer patients are certainly justified. PMID- 22777998 TI - Towards a simplified definition of childhood obesity? A focus on the extended IOTF references. PMID- 22777999 TI - Regression trees for predicting mortality in patients with cardiovascular disease: what improvement is achieved by using ensemble-based methods? AB - In biomedical research, the logistic regression model is the most commonly used method for predicting the probability of a binary outcome. While many clinical researchers have expressed an enthusiasm for regression trees, this method may have limited accuracy for predicting health outcomes. We aimed to evaluate the improvement that is achieved by using ensemble-based methods, including bootstrap aggregation (bagging) of regression trees, random forests, and boosted regression trees. We analyzed 30-day mortality in two large cohorts of patients hospitalized with either acute myocardial infarction (N = 16,230) or congestive heart failure (N = 15,848) in two distinct eras (1999-2001 and 2004-2005). We found that both the in-sample and out-of-sample prediction of ensemble methods offered substantial improvement in predicting cardiovascular mortality compared to conventional regression trees. However, conventional logistic regression models that incorporated restricted cubic smoothing splines had even better performance. We conclude that ensemble methods from the data mining and machine learning literature increase the predictive performance of regression trees, but may not lead to clear advantages over conventional logistic regression models for predicting short-term mortality in population-based samples of subjects with cardiovascular disease. PMID- 22778000 TI - Direct correlation between electric and structural properties during solidification of poly(3-hexylthiophene) drop-cast films. AB - Structural and electrical properties of semicrystalline P3HT cast films onto Si/SiO(2) surface are studied during the solidification under applied electric field in lateral OFET geometry. During evaporation of the solvent, the formation of P3HT crystallites is monitored simultaneously by time-resolved X-ray diffraction and by source-drain current measurements. The electrical current is reaching its maximum in two pronounced regimes already before complete solidification of the polymer as detected by X-ray diffraction intensities. The monitored complex time dependence of current and X-ray intensities reveals a highest conducting level for the gel-like state. PMID- 22778001 TI - Assessing large spatial scale landscape change effects on water quality and quantity response in the lower Athabasca River basin. AB - Increased land use intensity has been shown to adversely affect aquatic ecosystems. Multiple landscape stressors interact over space and time, producing cumulative effects. Cumulative Effects Assessment (CEA) is the process of evaluating the impact a development project may have on the ecological surroundings, but several challenges exist that make current approaches to cumulative effects assessment ineffective. The main objective of this study was to compare results of different methods used to link landscape stressors with stream responses in a highly developed watershed, where past work has shown that the river has experienced significant water quality and quantity changes to improve approaches to CEA. The study site was the lower reaches of the Athabasca River, Canada that have been subjected to a diverse range of intense anthropogenic developments since the late 1960s. Linkages between landscape change and river response were evaluated using correlation analyses, stepwise, multiple regression, and regression trees. Notable landscape changes include increased industrial development and forest cut-blocks, made evident from satellite imagery and supporting ancillary data sets. Simple regression analyses showed water use was closely associated with total phosphorus (TP) and Na(+) concentrations, as well as specific conductance. The regression trees for total organic carbon (TOC), TP, and Na(+) showed that the landscape variables that appear as the first characteristic were the same variables that showed significant relations for their respective simple regression models. Simple, stepwise, and multiple regressions in conjunction with regression trees were useful in this study for capturing the strongest associations between landscape stressors and river response variables. The results highlight the need for improved scaling methods and monitoring strategies crucial to managing cumulative effects to river systems. PMID- 22778002 TI - Immediate reconstruction of maxillectomy defects using anterolateral thigh free flap in patients from a low resource region. AB - OBJECTIVES/HYPOTHESIS: To report the reliability and reconstructive outcome of using anterolateral thigh (ALT) flap with or without titanium mesh to repair maxillectomy defects in a patient from a low resource region (LRR). STUDY DESIGN: Retrospective review. METHODS: Clinical data of patients with oral-maxillofacial cancers who underwent maxillectomy and reconstruction using ALT flap in two tertiary cancer centers in southern China were retrospectively reviewed. Reconstructive techniques, flap survival, postoperative oral functions, and surgical complications were reported. RESULTS: Apart from one total flap loss, 18 of the 19 free ALT flaps survived. Titanium mesh was used in two patients with total maxillectomy defects. Eighteen of the 19 patients resumed a normal oral diet. Fourteen patients had good speech, except one patient with poor pronunciation, and four patients had average speech. One patient presented with postoperative palatal fistula. No other complications were observed. CONCLUSIONS: The application of ALT flaps with or without titanium mesh to repair maxillectomy defects is straightforward and reliable and has an acceptable reconstructive outcome. It might be a suitable procedure for patients from an LRR. PMID- 22778003 TI - Fabrication of flexible MoS2 thin-film transistor arrays for practical gas sensing applications. AB - By combining two kinds of solution-processable two-dimensional materials, a flexible transistor array is fabricated in which MoS(2) thin film is used as the active channel and reduced graphene oxide (rGO) film is used as the drain and source electrodes. The simple device configuration and the 1.5 mm-long MoS(2) channel ensure highly reproducible device fabrication and operation. This flexible transistor array can be used as a highly sensitive gas sensor with excellent reproducibility. Compared to using rGO thin film as the active channel, this new gas sensor exhibits much higher sensitivity. Moreover, functionalization of the MoS(2) thin film with Pt nanoparticles further increases the sensitivity by up to ~3 times. The successful incorporation of a MoS(2) thin-film into the electronic sensor promises its potential application in various electronic devices. PMID- 22778004 TI - Graphene sheet orientation of parent material exhibits dramatic influence on graphene properties. AB - The production of graphene from various sources has garnered much attention in recent years with the development of methods that range from "bottom-up" to "top down" approaches. The top-down approach often requires thermal treatment to obtain a few-layered and lowly oxygenated graphene sheets. Herein, we demonstrate the production of graphene through oxidation and thermal-reduction/exfoliation of two sources of differently orientated graphene sheets: multiwalled carbon nanotubes (MWCNTs) and stacked graphene nanofibers (SGNFs). These two carbon nanofiber-like materials have similar axial (length: 5-9 MUm) and lateral dimensions (diameter: about 100 nm). We demonstrate that, whereas SGNFs exfoliate along the lateral plane between adjacent graphene sheets, carbon nanotubes exfoliate along its longitudinal axis and leads to opening of the carbon nanotubes owing to the built-in strain. Subsequent thermal exfoliation leads to graphene materials that have, despite the fact that their parent materials exhibited similar dimensions, dramatically different proportions and, consequently, materials properties. Graphene that was prepared from MWCNTs exhibited dimensions of about 5000*300 nm, whereas graphene that was prepared from SGNFs exhibited sheets with dimensions of about 50*50 nm. The density of defects and oxygen-containing groups on these materials are dramatically different, as are the electrochemical properties. We performed morphological, structural, and electrochemical characterization based on TEM, SEM, high resolution X-ray photoelectron spectroscopy, Raman spectroscopy, and cyclic voltammetry (CV) analysis on the stepwise conversion of the target source into the exfoliated graphene. Morphological and structural characterization indicated the successful chemical and thermal treatment of the materials. Our findings have shown that the orientation of the graphene sheets in starting materials has a dramatic influence on their chemical, material, and electrochemical properties. PMID- 22778005 TI - The influence of just-world beliefs on driving anger and aggressive driving intentions. AB - Decades of research demonstrate that the extent to which one believes the world is just can have important interpersonal consequences. Unfortunately, most of the commonly studied consequences are negative in nature. Guided by previous research demonstrating the buffering effect of just-world beliefs and anger, the present research explores how belief in a just world (BJW) may mitigate anger in the domain of driving anger and examines the limiting conditions of this effect. Study 1 demonstrated the expected negative relation between common measures of BJW and anger expression in a driving context. Study 2 found that the buffering effects of just-world beliefs and driver aggression were greater when BJW was violated (vs. not). Study 3 replicated the effects on aggression and anger and established a mediational role of anger on the buffering effects of just-world beliefs on thoughts and driver aggression. PMID- 22778007 TI - Discrete ephrin-B1 expression by specific layers of the primate retinogeniculostriate system continues throughout postnatal and adult life. AB - The molecular guidance cue ephrin-B1 has traditionally been associated with the early development of the visual system, encompassing retinocollicular mapping as well as development and maturation of synapses. Although little is known about its role in the visual system during the postnatal period and in adulthood, recent studies have demonstrated the expression of ephrin-B1 in the adult mouse brain, indicating a sustained role beyond early development. Therefore, we explored the spatiotemporal expression of ephrin-B1 in the postnatal and adult nonhuman primate visual system and demonstrated that a modulated expression continued following birth into adulthood in the lateral geniculate nucleus (LGN) and primary visual cortex (V1, striate cortex). This occurred in the layers involved in bidirectional geniculostriate communication: layers 3Bbeta, 4, and 6 of V1 and the parvocellular (P) and magnocellular (M) layers of the LGN. Furthermore, discrete gradients between the ipsi- and contralateral inputs of the P and M layers of the LGN evolved between 1 month following birth and the start of the critical period (3 months), and continued into adulthood. We also detected the postsynaptic expression of ephrin-B1 by excitatory cells in adult LGN and V1 and a subset of interneurons in adult V1, suggestive of a more global rather than subtype-specific role. Together these results suggest a possible role for ephrin B1 in the maturation of the primate retinogeniculostriate pathway throughout postnatal life, extending into adulthood. PMID- 22778006 TI - Organizational motifs for ground squirrel cone bipolar cells. AB - In daylight vision, parallel processing starts at the cone synapse. Cone signals flow to On and Off bipolar cells, which are further divided into types according to morphology, immunocytochemistry, and function. The axons of the bipolar cell types stratify at different levels in the inner plexiform layer (IPL) and can interact with costratifying amacrine and ganglion cells. These interactions endow the ganglion cell types with unique functional properties. The wiring that underlies the interactions among bipolar, amacrine, and ganglion cells is poorly understood. It may be easier to elucidate this wiring if organizational rules can be established. We identify 13 types of cone bipolar cells in the ground squirrel, 11 of which contact contiguous cones, with the possible exception of short-wavelength-sensitive cones. Cells were identified by antibody labeling, tracer filling, and Golgi-like filling following transduction with an adeno associated virus encoding for green fluorescent protein. The 11 bipolar cell types displayed two organizational patterns. In the first pattern, eight to 10 of the 11 types came in pairs with partially overlapping axonal stratification. Pairs shared morphological, immunocytochemical, and functional properties. The existence of similar pairs is a new motif that might have implications for how signals first diverge from a cone to bipolar cells and then reconverge onto a costratifying ganglion cell. The second pattern is a mirror symmetric organization about the middle of the IPL involving at least seven bipolar cell types. This anatomical symmetry may be associated with a functional symmetry in On and Off ganglion cell responses. PMID- 22778011 TI - Improving the standard of care for people with ankylosing spondylitis and a new approach to developing specialist ESP-Led AS clinics. AB - OBJECTIVES: In the UK, there is a wide variation in the quality of care that people with ankylosing spondylitis (AS) receive. People with AS require early diagnosis and referral to a specialist team to commence treatment and optimize outcome. METHODS: At East Kent Hospitals University Foundation Trust, a specialist clinic led by an extended scope practitioner (ESP) physiotherapist has been set up for the assessment and monitoring of patients with AS. This report describes the service provided by the AS clinic. RESULTS: Over eight years, the number of patients seen has risen from 62 to 352, and annual consultations from 186 to 986, with an average of 2.8 visits per patient per year. Ninety-seven patients have started treatment with a Tumour Necrosis Factor (TNF) blocker. The service has expanded by the addition of a support worker and biologic clinics. CONCLUSION: For the Trust, the specialist service provides an improved quality of care and cost-effective use of staff resources. Evaluation has demonstrated that patients welcome the new service. PMID- 22778010 TI - General population norms for the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI). AB - BACKGROUND: Metastatic renal cell cancer is associated with poor long-term survival and has no cure. Traditional clinical endpoints are best supplemented by patient-reported outcomes designed to assess symptoms and function. Normative data was obtained on the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Kidney Symptom Index (NFKSI) to aid in score interpretation and planning of future trials. METHODS: General population data were obtained from 2000 respondents, who completed the 19-item NFKSI-19, as well the SF-36 (Short Form 36-item instrument) and the PROMIS-29 (29-item Patient Reported Outcomes Measurement Information System), both general health status measures. Basic demographic and self-reported comorbidity data were also collected. RESULTS: The sample was 50% female, 85.7% caucasian, with an equal distribution across age bands from 18 years to 75 years and older. Most respondents (62.8%) had more than a high school education and reported an Eastern Cooperative Oncology Group performance status of normal activity without symptoms (63.4%). Score distributions on the NFKSI-19, its subscales, and individual items are summarized. CONCLUSIONS: The NFKSI-19 and its subscales now have scores for the general US population, allowing comparability to generic questionnaires such as the SF-36 and PROMIS-29. These data can be used to guide treatment expectations and plan future comparative effectiveness research using the scales. PMID- 22778009 TI - Clinical differences among mild cognitive impairment subtypes in Parkinson's disease. AB - Mild cognitive impairment is increasingly recognized as a construct in Parkinson's disease (PD) and occurs in about 25% of nondemented PD patients. Although executive dysfunction is the most frequent type of cognitive deficit in PD, the cognitive phenotype of PD mild cognitive impairment (PD-MCI) is broad. PD MCI subtypes are represented by amnestic and nonamnestic domain impairment as well as single- and multiple-domain impairment. However, it is unclear whether patients with different PD-MCI subtypes also differ in other clinical characteristics in addition to cognitive profile. We studied 128 PD-MCI subjects at our Movement Disorders center, comparing clinical, motor, and behavioral characteristics across the PD-MCI subtypes. We found varying proportions of impairment subtypes: nonamnestic single domain, 47.7%; amnestic multiple domain, 24.2%; amnestic single domain, 18.8%; and nonamnestic multiple domain, 9.5%. Attentional/executive functioning and visuospatial abilities were the most frequently impaired domains. PD-MCI subtypes differed in their motor features, with nonamnestic multiple-domain PD-MCI subjects showing particularly pronounced problems with postural instability and gait. Differences among PD-MCI subtypes in age, PD duration, medication use, mood or behavioral disturbances, and vascular disease were not significant. Thus, in addition to differing cognitive profiles, PD-MCI subtypes differed in motor phenotype and severity but not in mood, behavioral, or vascular comorbidities. Greater postural instability and gait disturbances in the nonamnestic multiple-domain subtype emphasize shared nondopaminergic neural substrates of gait and cognition in PD. Furthermore, increased burden of cognitive dysfunction, rather than type of cognitive deficit, may be associated with greater motor impairment in PD-MCI. PMID- 22778012 TI - Simultaneous enantiomeric determination of propranolol, metoprolol, pindolol, and atenolol in natural waters by HPLC on new polysaccharide-based stationary phase using a highly selective molecularly imprinted polymer extraction. AB - A simple high performance liquid chromatography method HPLC-UV for simultaneous enantiomeric determination of propranolol, metoprolol, pindolol, and atenolol in natural water samples was developed and validated, using a molecularly imprinted polymer solid-phase extraction. To achieve this purpose, Lux((r)) Cellulose 1/Sepapak-1 (cellulose tris-(3,5-dymethylphenylcarbamate)) (Phenomenex, Madrid, Spain) chiral stationary phase was used in gradient elution and normal phase mode at ambient temperature. The gradient elution program optimized consisted of a progressive change of the mobile phase polarity from n-hex/EtOH/DEA 90/10/0.5 (v/v/v) to 60/40/0.5 (v/v/v) in 13 min, delivered at a flow rate of 1.3 ml/min and a sudden change of flow rate to 2.3 ml/min in 1 min. Critical steps in any molecularly imprinted polymer extraction protocol such as the flow rate to load the water sample in the cartridges and the breakthrough volume were optimized to obtain the higher extraction recoveries for all compounds. In optimal conditions (100 ml breakthrough volume loaded at 2.0 ml/min), extraction recoveries for the four pairs of beta-blockers were near 100%. The MIP-SPE-HPLC-UV method developed demonstrates good linearity (R(2) >= 0.99), precision, selectivity, and sensitivity. Method limit detection was 3.0 ug/l for propranolol and pindolol enantiomers and 20.0 and 22.0 ug/l for metoprolol and atenolol enantiomers, respectively. The proposed methodology should be suitable for routine control of these emerging pollutants in natural waters for a better understanding of the environmental impact and fate. PMID- 22778013 TI - A versatile ligand platform that supports Lewis acid promoted migratory insertion. PMID- 22778015 TI - Analysing covariates with spike at zero: a modified FP procedure and conceptual issues. AB - In epidemiology and in clinical research, risk factors often have special distributions. A common situation is that a proportion of individuals have exposure zero, and among those exposed, we have some continuous distribution. We call this a 'spike at zero'. Examples for this are smoking, duration of breastfeeding, or alcohol consumption. Furthermore, the empirical distribution of laboratory values and other measurements may have a semi-continuous distribution as a result of the lower detection limit of the measurement. To model the dose response function, an extension of the fractional polynomial approach was recently proposed. In this paper, we suggest a modification of the previously suggested FP procedure. We first give the theoretical justification of this modified procedure by investigating relevant distribution classes. Here, we systematically derive the theoretical shapes of dose-response curves under given distributional assumptions (normal, log normal, gamma) in the framework of a logistic regression model. Further, we check the performance of the procedure in a simulation study and compare it to the previously suggested method, and finally we illustrate the procedures with data from a case-control study on breast cancer. PMID- 22778016 TI - Identification of two inherited copy number variants in a male with autism supports two-hit and compound heterozygosity models of autism. AB - Autism is a childhood-onset neurodevelopmental disorder with complex genetic mechanism underlying its etiology. Recent studies revealed that a few single de novo copy number variants of genomic DNA (copy number variants [CNVs]) are pathogenic and causal in some sporadic cases, adding support to the hypothesis that some sporadic autism might be caused by single rare mutation with large clinical effect. In this study, we report the detection of two novel private CNVs simultaneously in a male patient with autism. These two CNVs include a microduplication of ~4.5 Mb at chromosome 4q12-13.1 that was transmitted from his mother and a microdeletion of ~1.8 Mb at 5q32 that was transmitted from his father. Several genes such as LPHN3, POU4F3, SH3RF2, and TCERG1 mapped to these two regions have psychiatric implications. However, the parents had only mild degree of attention deficit symptoms but did not demonstrate any obvious autistic symptoms or psychopathology. Our findings indicate that each of these two CNVs alone may not be pathogenic enough to cause clinical symptoms in their respective carriers, and hence they can be transmitted within each individual family. However, concomitant presence of these two CNVs might result in the clinical phenotypes of the affected patient reported here. Thus, our report of this family may represent an example to show that two hits of CNV and the presence of compound heterozygosity might be important mechanisms underlying the pathogenesis of autism. PMID- 22778018 TI - Individual and class moral disengagement in bullying among elementary school children. AB - A cross-sectional study from a sample of 663 elementary school children assessed the four sets of moral disengagement mechanisms conceptualized by Bandura (i.e., cognitive restructuring, minimizing one's agentive role, disregarding/distorting the consequences, blaming/dehumanizing the victim) at both the individual and the class level. Additionally, an analysis of the relations of these mechanisms to pro-bullying behavior was conducted. Multilevel analysis showed a significant relationship between cognitive restructuring and individual pro-bullying behavior. Moreover, between-class variability of pro-bullying behavior was positively related to minimizing one's agentive role and blaming/dehumanizing the victim at the class level. Conversely, class disregarding/distorting the consequences was negatively associated with between-class variation in the outcome behavior. Implications for understanding the role of morality in children's bullying are discussed. PMID- 22778019 TI - Induction gemcitabine and oxaliplatin therapy followed by a twice-weekly infusion of gemcitabine and concurrent external-beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer: a single institutional experience. AB - BACKGROUND: Chemoradiotherapy (CRT) may render curative resection feasible in patients with locally advanced pancreatic carcinoma (LAPC). The authors previously demonstrated the achievement of significant disease control and a median survival of 14 months by CRT in patients with LAPC. In this study, they evaluated the use of induction chemotherapy followed by a CRT neoadjuvant protocol. METHODS: Patients first received induction gemcitabine and oxaliplatin (GEMOX) (gemcitabine 1000 mg/m(2), oxaliplatin 100 mg/m(2)). Patients without disease progression then received gemcitabine twice weekly (50 mg/m(2) daily) concurrent with radiotherapy (50.4 grays) and were re-evaluated for resectability. RESULTS: Thirty-nine patients (15 with borderline resectable disease and 24 with unresectable disease) entered the study. The treatment was well tolerated. Disease control was obtained in 29 of 39 patients. Two patients progressed after GEMOX, and 7 progressed after CRT. After a median follow-up of 13 months, the median progression-free survival (PFS) was 10.2 months. The median PFS of patients with borderline resectable and unresectable disease was 16.6 and 9.1 months, respectively (P = .056). For the whole group, the median overall survival (OS) was 16.7 months (27.8 months for patients with borderline resectable disease, 13.3 for patients with unresectable disease; P = .045). Eleven patients (9 with borderline resectable disease and 2 with unresectable disease at diagnosis) underwent successful resection. Patients who underwent resection had a significantly longer median PFS compared with nonresected patients (19.7 months vs 7.6 months, respectively). The median OS among resected and nonresected patients was 31.5 months and 12.3 months, respectively (P < .001). CONCLUSIONS: The current results indicated that induction GEMOX followed by CRT is feasible in patients with LAPC. Both those with borderline resectable disease and those with unresectable disease received clinical benefit, a chance to obtain resectability, and improved survival. The authors concluded that this protocol warrants further evaluation. PMID- 22778020 TI - Thyroidectomy with late identification of recurrent laryngeal nerve. PMID- 22778021 TI - Analysis of fluoroquinolones in animal feeds by liquid chromatography with fluorescence detection. AB - An analytical method for the analysis of six fluoroquinolones (FQs) in animal feeds was developed. The sample treatment consists of a simple and rapid extraction of the analytes by manual shaking with an acetonitrile-water mixture containing hydrochloric acid without further sample cleanup. Matrix effects were minimized by diluting the extract with water. Determination was carried out by liquid chromatography using fluorimetric detection. The method was validated in house in four different feed matrices (poultry, cow, pig, and lamb feed). Mean recoveries ranging from 80 to 105%, with relative standard deviations below 12%, were achieved from spiked animal feed samples on the 0.2-2.0 MUg/g level. No relevant differences were observed between the studied feeds, this ensuring that the method was reliable for a wide variety of feed matrices. Decision limit and detection capability values are below 0.08 and 0.13 mg/kg, respectively, for most FQs. The results obtained demonstrate the feasibility of the analytical method developed for a routine use to control the illegal use of these substances in feeding stuffs. PMID- 22778022 TI - No association between the type 2 diabetes mellitus susceptibility gene, SLC30A8 and schizophrenia in a Chinese population. AB - BACKGROUND: The co-occurrence of schizophrenia and type 2 diabetes mellitus (T2DM) has been well documented. Recent genome-wide association studies and meta analyses have shown robust associations of the solute carrier family 30 member 8 (SLC30A8) gene variants with T2DM in various populations. We examined the involvement of the SLC30A8 in the susceptibility to schizophrenia in a Han Chinese population. METHODS: The SLC30A8 rs13266634 gene polymorphism was genotyped in 837 chronic schizophrenic and 1109 unrelated healthy controls by using a case control design. We also assessed clinical symptoms. RESULTS: There were no significant differences in the rs13266634 genotype (chi(2) = 1.95, df = 2, p = 0.38) and allele (chi(2) = 0.47, df = 1, p = 0.50) distributions between the patient and control groups. There was no association between rs13266634 and clinical symptoms. CONCLUSION: The SLC30A8 gene variation does not appear to contribute a genetic basis for the co-occurrence of schizophrenia and T2DM. PMID- 22778023 TI - Physiotherapy provision following discharge after total hip and total knee replacement: a survey of current practice at high-volume NHS hospitals in England and wales. AB - BACKGROUND: Total hip replacement (THR) and total knee replacement (TKR) are two common elective orthopaedic procedures, and the provision of physiotherapy for patients after discharge is variable, with evidence for best practice remaining uncertain. AIMS AND OBJECTIVES: To determine the standard physiotherapy service offered to patients following discharge after THR and TKR. METHODS: A telephone survey was carried with clinicians at 24 high-volume NHS orthopaedic centres in England and Wales. Information was gathered on standard physiotherapy provision and categorized into; no routine physiotherapy, outpatient physiotherapy (including one-to-one and group), home-based physiotherapy or other physiotherapy (including telephone consultation and drop-in services). RESULTS: No centres surveyed referred patients to outpatient physiotherapy as a routine pathway of care following THR. Eleven centres provided group physiotherapy to patients after discharge following TKR compared with five centres providing one-to-one outpatient physiotherapy. CONCLUSION: The provision of physiotherapy following discharge after TKR is a more common practice than after THR, where ongoing physiotherapy is provided depending upon clinical need. Group exercises are the favoured destination for patients following TKR in high-volume centres. PMID- 22778025 TI - Infertility in women with systemic lupus erythematosus: comment on the article by Clowse et al. PMID- 22778024 TI - Rab11 regulates planar polarity and migratory behavior of multiciliated cells in Xenopus embryonic epidermis. AB - BACKGROUND: Xenopus embryonic skin is composed of the superficial layer with defined apicobasal polarity and the inner layer lacking the apical domain. Multiciliated cells (MCCs) originate in the inner layer of the epidermal ectoderm and subsequently migrate to the surface. How MCCs acquire the apicobasal polarity and intercalate into the superficial layer during neurulation is largely unknown. As Rab11-dependent vesicle trafficking has been implicated in ciliary membrane assembly and in apical domain formation in epithelial cells, we assessed the involvement of Rab11 in MCC development. RESULTS: Here we report that Rab11 is specifically enriched and becomes apically polarized in skin MCCs. Interference with Rab11 function by overexpression of a dominant negative mutant or injection of a specific morpholino oligonucleotide inhibited MCC intercalation into the superficial layer. Dominant negative Rab11-expressing MCC precursors revealed intrinsic apicobasal polarity, characterized by the apical domain, which is not normally observed in inner layer cells. Despite the presence of the apical domain, the cells with inhibited Rab11 function were randomly oriented relative to the plane of the tissue, thereby demonstrating a defect in planar polarity. CONCLUSIONS: These results establish a requirement for Rab11 in MCC development and support a two-step model, in which the initial polarization of MCC precursors is critical for their integration into the superficial cell layer. PMID- 22778027 TI - H2 activation and hydride transfer to olefins by Al(C6F5)3-based frustrated Lewis pairs. PMID- 22778026 TI - Decreased systemic IGF-1 in response to calorie restriction modulates murine tumor cell growth, nuclear factor-kappaB activation, and inflammation-related gene expression. AB - Calorie restriction (CR) prevents obesity and has potent anticancer effects associated with altered hormones and cytokines. We tested the hypothesis that CR inhibits MC38 mouse colon tumor cell growth through modulation of hormone stimulated nuclear factor (NF)-kappaB activation and protumorigenic gene expression. Female C57BL/6 mice were randomized (n = 30/group) to receive control diet or 30% CR diet. At 20 wk, 15 mice/group were killed for body composition analysis. At 21 wk, serum was obtained for hormone analysis. At 22 wk, mice were injected with MC38 cells; tumor growth was monitored for 24 d. Gene expression in excised tumors and MC38 cells was analyzed using real-time RT-PCR. In vitro MC38 NF-kappaB activation (by p65 ELISA and immunofluorescence) were measured in response to varying IGF-1 concentrations (1-400 ng/mL). Relative to controls, CR mice had decreased tumor volume, body weight, body fat, serum IGF-1, serum leptin, and serum insulin, and increased serum adiponectin (P < 0.05, each). Tumors from CR mice, versus controls, had downregulated inflammation- and/or cancer-related gene expression, including interleukin (IL)-6, IL-1beta, tumor necrosis factor-alpha, cyclooxygenase-2, chemokine (C-C motif) ligand-2, S100A9, and F4/80, and upregulated 15-hydroxyprostaglandin dehydrogenase expression. In MC38 cells in vitro, IGF-1 increased NF-kappaB activation and NF-kappaB downstream gene expression (P < 0.05, each). We conclude that CR, in association with reduced systemic IGF-1, modulates MC38 tumor growth, NF-kappaB activation, and inflammation-related gene expression. Thus, IGF-1 and/or NF-kappaB inhibition may pharmacologically mimic the anticancer effects of CR to break the obesity colon cancer link. PMID- 22778028 TI - Thiophene-coated functionalized M12L24 spheres: synthesis, characterization, and electrochemical properties. PMID- 22778029 TI - The food contaminant and nephrotoxin ochratoxin A enhances Wnt1 inducible signaling protein 1 and tumor necrosis factor-alpha expression in human primary proximal tubule cells. AB - SCOPE: The underlying molecular mechanisms of nanomolar ochratoxin A (OTA) concentrations, especially those on pathophysiological relevant gene expression in target tissue and underlying signaling mechanisms are unknown. METHODS AND RESULTS: qPCR arrays showed that 14 days exposure of human primary proximal tubule cells to 10 nM OTA influences the expression of genes that are related to inflammation, malignant transformation, and epithelial-to-mesenchymal transition. Wnt1 inducible signaling protein 1 (WISP1), an oncogenic, and profibrotic growth factor, turned out to be the gene with the strongest upregulation. Its expression, and that of TNF-alpha, an important inflammatory mediator, was further investigated in human renal cells and in primary human lung fibroblasts. OTA-induced upregulation of WISP1 and TNF-alpha occurs only in renal cells. Inhibition of ERK1/2 activation reverses the effect of OTA on WISP1 and TNF-alpha expression. Wnt or other signaling pathways were not involved. Upregulation of WISP1 and TNF-alpha occured independently of each other. CONCLUSION: Long-term exposure of human kidney cells with OTA concentrations expectable in renal tissue due to average dietary intake leads in an ERK1/2-dependent manner to pathogenetic alterations of gene expression, notably WISP1 and TNF-alpha. Renal long-term risk by OTA is actually not excludable and argues for low but rational safety levels. PMID- 22778030 TI - Middle ear myoclonus associated with forced eyelid closure in children: diagnosis and treatment outcome. AB - OBJECTIVES/HYPOTHESIS: Forceful eyelid closure syndrome (FECS) was first reported at the Proceedings of the Second International Tinnitus Seminar in 1983. The main symptom of this syndrome is a spontaneous muscular tinnitus related only to forced eye closure, specifically the voluntary contraction of the periorbital muscles. Although investigation of the syndrome was initiated >100 years ago, only four cases have been published in the past 20 years. We report six cases of middle ear myoclonus tinnitus diagnosed as FECS in children and discuss issues surrounding the diagnosis and treatment of this syndrome. STUDY DESIGN: Retrospective case series. METHODS: From 2009 to 2011, six children complaining of clicking or crackling sounds in their ears presented at Seoul St. Mary's Hospital. Endoscopic examination and recording of the tympanic membrane were performed while the patients were asked to close their eyes forcefully. Audiologic studies including acoustic reflex decay and static compliance were performed for documentation of the movement of the tympanic membrane. Triggering factors of FECS in the children were carefully evaluated. RESULTS: Synchronous movement of the tympanic membrane in response to forced eye closure on endoscopic examination was the most reliable finding to diagnose FECS. Acoustic reflex decay and other impedance audiogram findings showed irregular perturbations during forced eye closure, which led to diagnosis of the tinnitus as middle ear myoclonus. Most of the patients had triggering factors for FECS. Reassurance and removal of the triggering or causal factors with or without medication improved clicking sounds coming from middle ear myoclonus. CONCLUSIONS: FECS is a rare clinical entity and can be easily missed in routine clinical examination. We suggest that patients, especially children, with clicking or crackling tinnitus should be evaluated for FECS using proper diagnostic tools. A possible mechanism of FECS in children postulated from our case review is suggested. PMID- 22778031 TI - 1,3,5-Benzenetriamine double- and triple-decker molecules. PMID- 22778032 TI - Optimization of ion-pair based hollow fiber liquid phase microextraction combined with HPLC-UV for the determination of methimazole in biological samples and animal feed. AB - Ion-pair based hollow fiber liquid phase microextraction (IP-HFLPME) coupled with high performance liquid chromatography-ultraviolet detection was applied for the preconcentration and determination of methimazole in biological samples and animal feed. Optimization of the conditions for the high extraction efficiency was studied simultaneously using the experimental design. For the first step, the Plackett-Burman design was applied to screen the significant factors on the extraction efficiency. Central composite design (CCD) was then used for the optimization of important factors and the response surface equations were obtained. The optimum experimental conditions were donor phase pH, 12.2; extraction temperature, 45 degrees C; extraction time, 50 min; sodium perchlorate concentration, 1.5 M; cetyltrimethylammonium bromide concentration, 0.65 mM, and without salt addition in donor phase. The limit of detection and the dynamic linear range were in the range of 0.1-0.7 MUg L(-1) and 0.5-1000 MUg L(-1), respectively. Preconcentration factors were obtained in the range of 93-155 in different matrices. Finally, the performance of the proposed method was tested for the determination of trace amounts of methimazole in plasma, urine, bovine milk, and animal feed samples, and satisfactory results were obtained (RSDs < 7.1%). PMID- 22778033 TI - Body mass index, obesity, and prevalent gout in the United States in 1988-1994 and 2007-2010. AB - OBJECTIVE: To determine the association and prevalence of gout among overweight, obese, and morbidly obese segments of the US population. METHODS: Among participants (age >=20 years) of the National Health and Nutrition Examination Surveys in 1988-1994 and 2007-2010, gout status was ascertained by self-report of a physician diagnosis. Body mass index (BMI) was examined in categories of <18.5 kg/m(2) , 18.5-24.9 kg/m(2) , 25-29.9 kg/m(2) , 30-34.9 kg/m(2) , and >=35 kg/m(2) and as a continuous variable. The cross-sectional association of BMI category with gout status was adjusted for demographic and obesity-related medical disorders. RESULTS: In the US, the crude prevalence of gout was 1-2% among participants with a normal BMI (18.5-24.9 kg/m(2) ), 3% among overweight participants, 4-5% with class I obesity, and 5-7% with class II or class III obesity. The adjusted prevalence ratio comparing the highest to a normal BMI category was 2.46 (95% confidence interval [95% CI] 1.44-4.21) in 1988-1994 and 2.21 (95% CI 1.50-3.26) in 2007-2010. Notably, there was a progressively greater prevalence ratio of gout associated with successively higher categories of BMI. In both survey periods, for an average American adult standing 1.76 meters (5 feet 9 inches), a 1-unit higher BMI, corresponding to 3.1 kg (~6.8 pounds) greater weight, was associated with a 5% greater prevalence of gout, even after adjusting for serum uric acid (P < 0.001). CONCLUSION: Health care providers should be aware of the elevated burden of gout among both overweight and obese adults, applicable to both women and men, and observed among non-Hispanic whites, non-Hispanic African Americans, and Mexican Americans in the US. PMID- 22778034 TI - The origin of the stapes and relationship to the otic capsule and oval window. AB - BACKGROUND: The stapes, an ossicle found within the middle ear, is involved in transmitting sound waves to the inner ear by means of the oval window. There are several developmental problems associated with this ossicle and the oval window, which cause hearing loss. The developmental origin of these tissues has not been fully elucidated. RESULTS: Using transgenic reporter mice, we have shown that the stapes is of dual origin with the stapedial footplate being composed of cells of both neural crest and mesodermal origin. Wnt1cre/Dicer mice fail to develop neural crest-derived cartilages, therefore, have no middle ear ossicles. We have shown in these mice the mesodermal stapedial footplate fails to form and the oval window is induced but underdeveloped. CONCLUSIONS: If the neural crest part of the stapes fails to form the mesodermal part does not develop, indicating that the two parts are interdependent. The stapes develops tightly associated with the otic capsule, however, it is not essential for the positioning of the oval window, suggesting that other tissues, perhaps within the inner ear are needed for oval window placement. PMID- 22778035 TI - Group-based trajectories of depressive symptoms and the predictors in the older population. AB - PURPOSE: The goals of this study were to examine the group-based trajectories of depressive symptoms over an extended period among the older people and to identify the risk factors by gender. METHODS: The 18-year data used in this study came from a multiple-wave nationwide survey of older Taiwanese population. A group-based trajectory analysis method was used to identify the trajectories, and risk factors at baseline and previous depressive symptoms were used as predictors for the trajectories. RESULTS: Six trajectories were identified within the total sample, and females were more likely to be in the increasing and declining trajectories than males. When the data were divided by gender, four trajectories for males and four trajectories for females were identified: low, medium, declining, and increasing. Higher-level trajectories of depressive symptoms were related to more chronic diseases, lower physical function, lower economic satisfaction, and previous depressive symptoms for both the older men and women. Less social support and social participation were related to higher depressive symptom trajectories, particularly for men. DISCUSSION: Older females may experience more emotional fluctuation than male elderly, thus changes in psychosocial health for female elderly need to be considered by health professionals and families. Social support and social participation are protective against depressive symptoms for the higher-level trajectory groups, and older men, in particular, are more sensitive to these two social-health related variables. PMID- 22778039 TI - 'In one ear and out the other - it's a lot to take in': a qualitative study exploring the informational needs of patients with ANCA-associated vasculitis. AB - OBJECTIVES: To explore the informational needs of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Three focus groups and eight one-to-one interviews were conducted with patients with AAV. A purposeful sample of 15 patients (ten female) [disease: three Churg-Strauss syndrome (CSS); nine granulomatosis with polyangiitis (GPA); one microscopic polyangiitis (MPA); two polyarteritis nodosa (PAN)] participated in the focus groups. Eight (five female) (disease: three CSS; four GPA; one MPA) participated in the one-to-one interviews. A semi-structured interview guide was used to explore patients' experiences of informational needs. The focus groups and interviews were audio recorded and transcribed verbatim, and analysed using the framework technique. RESULTS: Emergent themes were: reaction to diagnosis, need for information on disease management and access to knowledgeable practitioners. When given the initial diagnosis, all patients described themselves as being too ill to take in information and that they later found it difficult to find information. Most information received at diagnosis was in the form of verbal information given by the hospital doctor. Patients wanted positive but truthful information in the form of a booklet. CONCLUSIONS: Receiving the diagnosis of a rare, potentially life-threatening disease and then dealing with its complex treatment causes anxiety and fear and can impede information retention and recall. Patients want information on diagnosis and treatment but this should be tailored to individual needs, including timing that is appropriate for them. All patients wanted the opportunity to discuss their illness and its management with a knowledgeable healthcare practitioner but also wanted printed forms of information to assimilate at their own pace. PMID- 22778040 TI - Energy transfer and concentration-dependent conformational modulation: a porphyrin-containing [3]rotaxane. AB - A zinc porphyrin-containing [3]rotaxane A was synthesized through a copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Energy donors and acceptor porphyrin were introduced to dibenzo[24]crown-8 (DB24C8) and dibenzyl ammonium (DBA) units of [3]rotaxane A to understand the intramolecular energy transfer process. Investigations of the photophysical properties of [3]rotaxane A demonstrated that the intramolecular efficient energy transfer readily occurred from the donors on the wheels to the porphyrin center on the axis. The fluorescence of energy donors in the region of 400 to 450 nm was efficiently absorbed by the porphyrin acceptor under irradiation at 345 nm, and finally a red light emission at about 600 nm was achieved. Further investigation indicated that the conformation of [3]rotaxane A was self-modulated by changing its concentration in CH(2)Cl(2). The triazole groups on the wheel coordinated or uncoordinated to Zn(2+) through intramolecular self-coordination with the change in the concentration of [3]rotaxane A in CH(2)Cl(2). Therefore, this conformational change was reversible in a non-coordinating solvent such as CH(2)Cl(2) but inhibited in a coordinating solvent such as THF. Such interesting behaviors were rarely observed in porphyrin derivatives. This self-modulation feature opens up the possibility of controlling molecular conformation by varying concentration. PMID- 22778036 TI - Higher maternal prenatal cortisol and younger age predict greater infant reactivity to novelty at 4 months: an observation-based study. AB - Distress-linked activation of the maternal hypothalamic-pituitary-adrenal (HPA) axis is considered a pathway by which affect regulation impacts the fetal milieu and neurodevelopment. There is little direct evidence for this conceptual model. In 103 women [mean age 27.45 (+/-5.65) years] at 36-38 weeks gestation, salivary cortisol was measured before/after stress tasks; distress questionnaires were completed. At 18.49 (+/-1.83) weeks, infants underwent the Harvard Infant Behavioral Reactivity Protocol assessing cry/motor responses to novelty; women reported on infant behavior and postnatal distress. Prenatal cortisol and distress were not significantly correlated (all ps > .10). Proportional odds logistic regressions showed that neither prenatal nor postnatal distress was associated with infant responses to the Harvard Protocol yet pre-stress cortisol and maternal age were: The odds of being classified as High Reactive were 1.60 times higher [95% CI: 1.04, 2.46] for each unit of added cortisol and .90 times lower [95% CI: .82, .99] for every additional year in maternal age. No associations were found between cortisol or prenatal distress and mother-rated infant behavior; postnatal distress was positively associated with mother-rated infant negative behavior (p = .03). Observer and mother-rated infant behavior were not associated (all ps > .05). Based on independent observations of infants in contrast to maternal perceptions, these results lend support to the hypothesis that pregnant women's HPA-axis activity influences infant behavior. The impact of maternal distress was not supported, except in so far as postnatal distress may increase the likelihood of making negative judgments about infant behavior. PMID- 22778041 TI - Milestones for Apheresis education. AB - Milestones represent the essential knowledge, skills, and attitudes required for the practice of a medical discipline. Defining these milestones for each medical specialty has become a focus for the American Council of Graduate Medical Education (ACGME). Practitioners of Apheresis Medicine come from a variety of medical specialties making it challenging to establish the essential educational milestones for all. The American Society for Apheresis (ASFA) has an interest in promoting standards of excellence for Apheresis Medicine. ASFA's Physician's Curriculum Content Committee is a group of physician educators in the field of Apheresis Medicine, both donor and therapeutic, from across the United States, who have met regularly for several years to discuss the appropriate educational milestones in Apheresis training. The committee members teach residents and fellows from Pathology, Transfusion Medicine, Hematology/Oncology, Nephrology and other specialties. In this document, we have outlined the basic set of Apheresis milestones required in the ACGME defined competency areas of Patient Care and Medical Knowledge. We have also recommended methods of evaluation and estimated the time necessary for the acquisition of these cognitive and behavioral elements. PMID- 22778042 TI - Caged-protein-confined bimetallic structural assemblies with mimetic peroxidase activity. PMID- 22778043 TI - Risk of post-tonsillectomy hemorrhage by clinical diagnosis. AB - OBJECTIVES/HYPOTHESIS: Obstructive sleep apnea (OSA) has been associated with upregulation of prothrombotic factors. We hypothesize that diagnosis of OSA may be protective against postoperative hemorrhage. This study investigates the relationships between preoperative clinical diagnosis and postoperative hemorrhage. STUDY DESIGN: Seven-year retrospective case-control study. METHODS: Medical records of tonsillectomy subjects with and without hemorrhage were reviewed for demographics, clinical diagnosis, and treatment. Clinical diagnoses included OSA confirmed by polysomnogram, sleep-disordered breathing (SDB), chronic tonsillitis, and a mixed group. RESULTS: A total of 9,023 tonsillectomy patients were identified (52.0% male, 48.0% female; mean age, 6.9 years). Of these, 2.4% (n = 212) presented with hemorrhage. There were 48 (22.6%) primary and 164 (77.4%) secondary hemorrhages. The control group consisted of 1,488 nonhemorrhage patients. A multivariate logistic regression analysis compared the two groups controlling for age, sex, and clinical diagnosis. OSA patients were half as likely to hemorrhage compared to chronic tonsillitis patients (P = .04). SDB patients also had a lower chance of hemorrhage compared to chronic tonsillitis patients; this result was not significant (P = .09). Patients older than 6 years had a higher hemorrhage rate (P < .001). CONCLUSIONS: This study demonstrates that patients with OSA may be less likely to have postoperative hemorrhage than patients with chronic tonsillitis. Younger age was associated with fewer hemorrhages. PMID- 22778044 TI - 1-Azido-1-alkynes: synthesis and spectroscopic characterization of azidoacetylene. PMID- 22778045 TI - Glial proteome changes in response to moderate hypothermia. AB - Reactive glia plays a central role in neuroinflammation associated with secondary damage after brain injury. In order to understand the global effects of therapeutic hypothermia on glial activation and neuroinflammation, we performed proteomic profiling of glial cultures following inflammatory stimulation and hypothermic exposure. Primary mixed glial cultures prepared from mouse brains were stimulated with lipopolysaccharide and interferon-gamma under normothermic (37 degrees C) or moderate hypothermic (29 degrees C) conditions, and their proteome profiles were compared by LC-ESI-MS/MS. Differentially expressed proteins were determined by high-throughput label-free quantification. Under hypothermic conditions, 64 and 16 proteins were upregulated (>=1.5-fold) and downregulated (<= 0.7-fold), respectively, compared to normothermic conditions. More importantly, hypothermia altered the abundance of 143 proteins that were either increased or decreased by inflammatory stimulation. The results were validated for several proteins (ICAM-1, STAT-1, YWHAB, and IFIT-3) by Western blot analysis. Pathway and network analysis indicate that hypothermia influences various biological functions of glia such as molecular transport, cell movement, immune response, cell death, and stress response. In conclusion, moderate hypothermia seems to have a significant effect on the protein expression profiles of brain glia and possibly ensuing neuroinflammation. These proteins may be involved in the protective mechanism of hypothermia against brain injuries. PMID- 22778046 TI - Aldosterone receptor antagonists in cardiovascular disease: a review of the recent literature and insight into potential future indications. AB - Randomized controlled trials demonstrate the efficacy of aldosterone receptor antagonists (spironolactone and eplerenone) as a useful pharmacologic intervention specifically in patients with New York Heart Association (NYHA) class III and IV heart failure, in patients with an ejection fraction <40% after myocardial infarction, and most recently in patients with mildly symptomatic heart failure. However, aldosterone receptor antagonists may be beneficial in a broader patient population. Aldosterone receptor antagonists can potentially serve as an antiarrhythmic pharmacologic agent for atrial and ventricular arrhythmias, an anti-ischemic medication in coronary artery disease through prevention of myocardial fibrosis and vascular damage, and as an agent in people with asymptomatic and mild heart failure (NYHA classes I and II) and diastolic heart failure. However, many clinicians remain reluctant to prescribe this highly efficacious pharmacologic therapy for a variety of reasons, including concerns about polypharmacy and hyperkalemia. Recent observational analysis demonstrates that less than one-third of eligible patients hospitalized with heart failure actually received aldosterone antagonist therapy. This article will review the current and potential future uses of aldosterone receptor antagonists across the entire spectrum of cardiovascular disease. The authors have no funding, financial relationships, or conflicts of interest to disclose. PMID- 22778048 TI - Selective unilateral lung ventilation in preterm infants with acquired bullous emphysema: a series of nine cases (Jakob et al.). PMID- 22778047 TI - Performance on an impulse control task is altered in adult rats exposed to amphetamine during adolescence. AB - Repeated exposure to psychostimulant drugs is associated with long-lasting changes in cognition, particularly in behavioral tasks that are sensitive to prefrontal cortex function. Adolescents may be especially vulnerable to these drug-induced cognitive changes because of the widespread adaptations in brain anatomy and function that are characteristic of normal development during this period. Here, we used a differential reinforcement of low rates of responding task in rats to determine if amphetamine (AMPH) exposure during adolescence would alter behavioral inhibition in adulthood. Between postnatal days (PND) 27 and 45, rats received every other day injections of saline or AMPH (3 mg/kg). At PND 125, rats were trained progressively through a series of four reinforcement schedules (DRL 5, 10, 15, and 30 s) that required them to withhold responding for the appropriate amount of time before a lever press was reinforced. Relative to controls, AMPH-treated rats displayed transient deficits in behavioral inhibition (i.e., decreases in efficiency ratio) that were only evident at DRL 5. In addition, they had increased responding during nonreinforced periods, which suggested increased perseveration and propensity to attribute incentive salience to reward-paired cues. Following challenge injections with AMPH (.25-1 mg/kg, i.p.), which were given 10 min before the start of DRL 30 test sessions, both groups exhibited dose-dependent decreases in efficiency. These results suggest that AMPH-induced alterations in incentive-motivation and perseveration are more robust and longer-lasting than its effects on impulse control. PMID- 22778051 TI - Facet-dependent photocatalytic properties of AgBr nanocrystals. AB - Polyhedral AgBr nanocrystals, evolved from cubes through truncated cubes and finally to high-symmetry octahedra, which corresponds to a progressive shrinkage of exposed {100} facets and enlargement of exposed {111} facets, are prepared by facile precipitation reactions. The as- prepared AgBr nanocrystals exhibit facet dependent catalytic properties, with the {111}-dominated octahedra showing the highest photocatalytic activities. PMID- 22778050 TI - Inflammatory airway responses by nasal inoculation of suspended particulate matter in NC/Nga mice. AB - To evaluate the allergic effect of airborne particulate matter (PM) on the airway, separated soluble supernatant (Sup) and insoluble precipitate (Pre) in suspended PM were inoculated into NC/Nga mice with a high sensitivity for mite allergens. Sup, Pre, or both Sup and Pre with or without pronase treatment were inoculated via the nasal route five times for sensitization and a challenge inoculation on the 11th day in NC/Nga mice. On the 14th day, mice were examined for airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, mRNA expression of Th1 and Th2 cytokines in the lung tissue, and histopathology. Synergistic effects of Sup and Pre were observed as increases in AHR and a histopathological change of Periodic acid-Schiff (PAS) staining. Increases in neutrophils, macrophages, and lymphocytes of BALF cells were dependent on Pre. The expression of IL-4 mRNA was increased by Sup, and those of IL-5 mRNA and Il-13 mRNA was increased by Sup and Pre. Augmented AHR, mRNA expression of IL-4, peribronchial inflammation, and PAS staining by Sup plus Pre were attenuated by treatment of Sup with pronase to digest proteins. These results suggest that some proteins of ambient PM may be important environmental factors for AHR and airway inflammation with the aid of insoluble particulates, although some soluble factors such as endotoxins cannot be ruled out. PMID- 22778052 TI - A novel bioassay platform using ferritin-based nanoprobe hydrogel. PMID- 22778049 TI - Current insights on the regenerative potential of the periosteum: molecular, cellular, and endogenous engineering approaches. AB - While century old clinical reports document the periosteum's remarkable regenerative capacity, only in the past decade have scientists undertaken mechanistic investigations of its regenerative potential. At a Workshop at the 2012 Annual Meeting of Orthopaedic Research Society, we reviewed the molecular, cellular, and tissue scale approaches to elucidate the mechanisms underlying the periosteum's regenerative potential as well as translational therapies engineering solutions inspired by its remarkable regenerative capacity. The entire population of osteoblasts within periosteum, and at endosteal and trabecular bone surfaces within the bone marrow, derives from the embryonic perichondrium. Periosteal cells contribute more to cartilage and bone formation within the callus during fracture healing than do cells of the bone marrow or endosteum, which do not migrate out of the marrow compartment. Furthermore, a current healing paradigm regards the activation, expansion, and differentiation of periosteal stem/progenitor cells as an essential step in building a template for subsequent neovascularization, bone formation, and remodeling. The periosteum comprises a complex, composite structure, providing a niche for pluripotent cells and a repository for molecular factors that modulate cell behavior. The periosteum's advanced, "smart" material properties change depending on the mechanical, chemical, and biological state of the tissue. Understanding periosteum development, progenitor cell-driven initiation of periosteum's endogenous tissue building capacity, and the complex structure-function relationships of periosteum as an advanced material are important for harnessing and engineering ersatz materials to mimic the periosteum's remarkable regenerative capacity. PMID- 22778053 TI - A home-based training program improves Taiwanese family caregivers' quality of life and decreases their risk for depression: a randomized controlled trial. AB - OBJECTIVES: Little is known about the longitudinal effects of training programs on family caregivers' health-related quality of life (HRQoL) and depressive symptoms over time. Therefore, the purpose of this study was to examine the effects of a home-based caregiver training program on HRQoL and depressive symptoms for family caregivers of older persons with dementia. METHODS: Outcomes (caregivers' HRQoL and depressive symptoms) were assessed before the training program (baseline), and at 2 weeks, 3 months, and 6 months afterwards. HRQoL was measured using the Medical Outcomes Study 36-item Short Form Survey, Taiwan version. Depressive symptoms were measured using the Chinese version Center for Epidemiologic Studies Depression Scale. RESULTS: Family caregivers who received the individualized home-based training program had better health outcomes in bodily pain (b = 12.37, p < 0.013), role disability due to emotional problems (b = 17.74, p < 0.013), vitality (b = 12.40, p < 0.001), better mental summary score (b = 5.14, p < 0.003), and decreased risk for depression (odds ratio = 0.15, confidence interval = 0.04-0.65, p < 0.013) than those in the control group during the 6 months following the training program. CONCLUSION: Our home-based caregiver training program improved caregivers' HRQoL, especially role limitations due to emotional problems, and decreased their risk for depression. PMID- 22778054 TI - Total synthesis of (+/-)-parvineostemonine. PMID- 22778055 TI - Positron-emission tomography pitfalls related to oral prosthesis. AB - This case report describes false-positive positron-emission tomography/computed tomography (PET/CT) findings related to oral prostheses and its implications in cancer surveillance. In head and neck cancer management, F18-flurodeoxyglucose (FDG) PET/CT is widely accepted for evaluating treatment response and detecting recurrence. Interpretation of FDG PET/CT images in this setting is often challenging due to various prostheses and reconstruction methods. Following surgery for squamous cell carcinoma of the maxillary alveolus, a 61-year-old female had a FDG PET/CT scan on a 7-month follow-up that showed high FDG uptake along the resection site. Clinical examination showed no signs of inflammation or recurrence. Repeat FDG PET/CT without the prosthesis was normal. The PET/CT attenuation-corrected images demonstrated high FDG uptake (standardized uptake value: 11.6) along the resection site corresponding to contrast-enhanced CT images of the lesion. PET/CT nonattenuation-corrected images also confirmed increased activity. Repeat PET/CT without the prosthesis was normal. FDG is not tumor specific; it can accumulate in inflammation, infection, and post-therapy settings. Metallic and high-density prostheses show radial artifacts on CT and falsely elevated FDG uptake on PET/ CT in adjacent areas. Salivary pooling may concentrate FDG. The presence of oral prostheses has not been described as a cause of this high level of activity. PET/CT images that demonstrate intense activity corresponding to dense structures should be viewed with caution. A detailed history and physical exam as well as knowledge of artifacts are pertinent for the managing physician. Laryngoscope, 2012. PMID- 22778056 TI - Synthesis of 1-octanol and 1,1-dioctyl ether from biomass-derived platform chemicals. AB - The happy medium: A new catalytic pathway for the synthesis of the linear primary C(8) alcohol products 1-octanol and dioctyl ether from furfural and acetone has been developed using retrosynthetic analysis. This opens a general strategy for the synthesis of medium-chain-length alcohols from carbohydrate feedstock. PMID- 22778057 TI - Targeting to overexpressed glucose-regulated protein 78 in gastric cancer discovered by 2D DIGE improves the diagnostic and therapeutic efficacy of micelles-mediated system. AB - The survivals of gastric cancer (GC) patients are associated with early diagnosis and effective treatments. Therefore, it is urgent for the discovery of early GC biomarkers and tumor-targeting therapeutics. The aim of this study was to uncover putative tissue biomarkers of GC using 2D DIGE and then apply one of these specific markers in GC treatment. We found three putative biomarkers of GC with significant differences in expression level compared to adjacent normal tissue, including glucose-regulated protein 78 (GRP78) and glutathione s-transferase pi (GSTpi) with increased expression level, and alpha-1 antitrypsin (A1AT) with reduced expression level. The overexpressed GRP78 was used as a targeted protein for guiding the drugs to tumor cells, leading to more effective treatment for GC xenografts. Our results demonstrated that the designated GRP78-binding peptide based on the sequence, WIFPWIQL, was selectively prone to recognize and bind to GC MKN45 cells in vitro, and also improve the delivery efficiency of polymeric micelles-encapsulated drugs into tumor cells and displayed better therapeutic outcome in experimental animals. This strategy of GRP78-mediated drug targeting system may bring chemotherapeutic drugs with more precise targeting to tumor cells, leading to minimize side effects on patients after chemotherapy. PMID- 22778058 TI - Preparation and in vitro characterization of SN-38-loaded, self-forming polymeric depots as an injectable drug delivery system. AB - This work describes the preparation and characterization of anticancer-loaded injectable polymeric depots that consisted of D,L-lactide (LA), epsilon caprolactone (CL), and poly(ethylene glycol) (PEG) or [poly(epsilon-caprolactone) random-poly(D,L-lactide)]-block-poly(ethylene glycol)-block-[poly(epsilon caprolactone)-random-poly(D,L-lactide)] (PLEC) copolymers for malignant gliomas treatment. PLECs were polymerized with different percentages of LA to deliver 7 ethyl-10-hydroxycamptothecin (SN-38), a highly potent anticancer drug. SN-38 loaded depots could form directly in phosphate buffer saline with more than 98% encapsulation efficiency. The release rate of SN-38 from depots was found to depend on the amount of LA in PLECs, loading content of SN-38 in the depots, and depot weight. Encapsulation of SN-38 inside depots could enhance the stability of SN-38 where all of SN-38 released after 60 days was in an active form. Depots without SN-38 were evaluated as noncytotoxic against U-87MG, whereas SN-38-loaded depots showed cytotoxic effect as a function of concentration. PMID- 22778059 TI - Serum levels of BMP-2, 4, 7 and AHSG in patients with degenerative joint disease requiring total arthroplasty of the hip and temporomandibular joints. AB - To date, there is no objective or reliable means of assessing the severity of degenerative joint disease (DJD) and need for joint replacement surgery. Hence, it is difficult to know when an individual with DJD has reached a point where total arthroplasty is indicated. The purpose of the present study is to determine whether serum levels of Alpha-2 HS-glycoprotein (AHSG) as well as bone morphogenetic proteins (BMP-2, 4, 7) can be used to predict the presence of severe DJD of the hip and/or temporomandibular joint (TMJ) (specifically: joints that require replacement). A total of 30 patients scheduled for arthroplasty (diseased) (15 HIP, 15 TMJ) and 120 age-matched controls (healthy/non-diseased) were included. Blood samples were collected from all patients >=8 weeks after the last arthroplasty. Concentrations of serum analytes were measured using enzyme linked immunosorbent assays, and these were compared between the Diseased and Healthy groups, utilizing the Mann-Whitney U-test. Patients with disease had significantly higher levels of BMP-2 and BMP-4 and lower levels of AHSG in serum compared to non-diseased humans (p < 0.01). Higher levels of BMP-2, 4 and reduced levels of AHSG appear to characterize patients who have DJD that is severe enough to require total joint replacement. Perhaps measurements of these proteins can be used to make objective decisions regarding the need for total arthroplasty as opposed to the current subjective approaches. PMID- 22778061 TI - Intravenous penicillin--still the first-line therapy for pediatric community acquired pneumonia. PMID- 22778060 TI - Remarkable enhancement of hole transport in top-gated N-type polymer field-effect transistors by a high-k dielectric for ambipolar electronic circuits. AB - A remarkable enhancement of p-channel properties is achieved in initially n channel dominant ambipolar P(NDI2OD-T2) organic field-effect transistors (OFETs) by the use of the fluorinated high-k dielectric P(VDF-TrFE). An almost two orders of magnitude increase in hole mobility (~0.11 cm(2) V(-1) s(-1) ) originates from a strong interface modification at the semiconductor/dielectric interface, which provides high-performance complementary-like inverters and ring oscillator circuits. PMID- 22778062 TI - Systematic curation and analysis of genomic variations and their potential functional consequences in snoRNA loci. AB - Small nucleolar RNAs (snoRNAs) are a class of noncoding functional RNAs which are involved in RNA modifications, like methylation and pseudouridylation of other RNAs. The snoRNA species of RNAs are characterized by conserved structural motifs they harbor which are also intricately related to their functionality. Though there have been reports of the involvement of snoRNAs in disease processes and anecdotal reports of genomic variations in snoRNA loci and their effects in modulating snoRNA function, there has been no systematic collection and analysis of variations in snoRNA loci. In this manuscript, we present the most comprehensive curation of genomic single nucleotide variations in human snoRNA loci, and their systematic computational analysis to reveal potential single nucleotide variations which could have functional effects. We show six single nucleotide variations in snoRNA loci could significantly alter snoRNA structure and could have potential implications in their functions. The compilation is available at the snoRNA locus specific variation database: http://genome.igib.res.in/snolovd conforming to the HGVS standards for nomenclature of genomic variants. PMID- 22778063 TI - Low-coordinate iron(I) and manganese(I) dimers: kinetic stabilization of an exceptionally short Fe-Fe multiple bond. PMID- 22778064 TI - Fabrication of nanofluidic biochips with nanochannels for applications in DNA analysis. AB - With the development of nanotechnology, great progress has been made in the fabrication of nanochannels. Nanofluidic biochips based on nanochannel structures allow biomolecule transport, bioseparation, and biodetection. The domain applications of nanofluidic biochips with nanochannels are DNA stretching and separation. In this Review, the general fabrication methods for nanochannel structures and their applications in DNA analysis are discussed. These representative fabrication approaches include conventional photolithography, interference lithography, electron-beam lithography, nanoimprint lithography and polymer nanochannels. Other nanofabrication methods used to fabricate unique nanochannels, including sub-10-nm nanochannels, single nanochannels, and vertical nanochannels, are also mentioned. These nanofabrication methods provide an effective way to form nanoscale channel structures for nanofluidics and biosensor devices for DNA separation, detection, and sensing. The broad applications of nanochannels and future perspectives are also discussed. PMID- 22778065 TI - Gene expression profiles of vitrified in vitro- and in vivo-derived bovine blastocysts. AB - Vitrification is becoming a preferred method for pre-implantation embryo cryopreservation. The objective of this study was to determine the differentially expressed genes of in vivo- and in vitro-produced bovine embryos after vitrification. In vitro- (IVF) and in vivo-derived (IVV) bovine blastocysts were identified as follows: in vitro-produced fresh (IVF-F), in vitro-produced vitrified (IVF-V), in vivo-derived fresh (IVV-F), in vivo-derived vitrified (IVV V). The microarray results showed that 53 genes were differentially regulated between IVF and IVV, and 121 genes were differentially regulated between fresh and vitrified blastocysts (P < 0.05). There were 6, 268, 962, and 17 differentially regulated genes between IVF-F * IVV-F, IVF-V * IVV-V, IVF-F * IVF V, and IVV-F * IVV-V, respectively (P < 0.05). While gene expression was significantly different between fresh and vitrified IVF blastocysts (P < 0.05), it was similar between fresh and vitrified IVV blastocysts. Significantly up regulated KEGG pathways included ribosome, oxidative phosphorylation, spliceosome, and oocyte meiosis in the fresh IVF blastocyst samples, while sphingolipid and purine metabolisms were up-regulated in the vitrified IVF blastocyst. The results showed that in vitro bovine blastocyst production protocols used in this study caused no major gene expression differences compared to those of in vivo-produced blastocysts. After vitrification, however, in vitro produced blastocysts showed major gene expression differences compared to in vivo blastocysts. This study suggests that in vitro-produced embryos are of comparable quality to their in vivo counterparts. Vitrification of in vitro blastocysts, on the other hand, causes significant up-regulation of genes that are involved in stress responses. PMID- 22778066 TI - 4-chloro-1,2-phenylenediamine induces apoptosis in Mardin-Darby canine kidney cells via activation of caspases. AB - 4-Chloro-1,2-phenylenediamine (4-Cl-o-PD) is a halogenated aromatic diamine that was used as a precursor for manufacturing permanent hair dyes. Despite its well documented mutagenic and carcinogenic effects in a number of in vitro and in vivo models, its cytotoxicity and mode of action have not received similar attention. Here, we investigated the effect of 4-Cl-o-PD on Mardin-Darby canine kidney cells. It induced apoptosis and the evidence suggests its initiation by reactive oxygen species (ROS). The results of various assays used show a dose-dependent (i) decrease in cell viability, (ii) increase in cells at sub-G1 phase and the G0/G1 phase arrested in cell cycle, (iii) increase in intracellular ROS accompanied by depletion of glutathione, and (iv) that apoptotic cell death probably involves activation of both intrinsic and extrinsic pathways. PMID- 22778070 TI - Suppository formulations as a potential treatment for nephropathic cystinosis. AB - Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised lysosomal levels of cystine in the cells of all the organs. It is treated by the 6-h oral administration of the aminothiol, cysteamine, which has an offensive taste and smell. In an attempt to reduce this frequency and improve the treatment, cysteamine-containing polyethylene glycol suppositories were prepared and evaluated for dissolution and stability. The results demonstrated that cysteamine release was complete after 30 min, and that there was a uniform drug distribution within the formulations. Twelve-month stability tests highlighted a potential incompatibility among some excipients, although stability was demonstrated for the cysteamine suppositories up to 6 months. These suppositories may provide a useful alternative to the current oral therapy for cystinosis. PMID- 22778071 TI - Analysis of secondary structure in proteins by chemical cross-linking coupled to MS. AB - Chemical cross-linking is an attractive technique for the study of the structure of protein complexes due to its low sample consumption and short analysis time. Furthermore, distance constraints obtained from the identification of cross linked peptides by MS can be used to construct and validate protein models. If a sufficient number of distance constraints are obtained, then determining the secondary structure of a protein can allow inference of the protein's fold. In this work, we show how the distance constraints obtained from cross-linking experiments can identify secondary structures within the protein sequence. Molecular modeling of alpha helices and beta sheets reveals that each secondary structure presents different cross-linking possibilities due to the topological distances between reactive residues. Cross-linking experiments performed with amine reactive cross-linkers with model alpha helix containing proteins corroborated the molecular modeling predictions. The cross-linking patterns established here can be extended to other cross-linkers with known lengths for the determination of secondary structures in proteins. PMID- 22778072 TI - Knee rotation in healthy individuals related to age and gender. AB - An external device ("the Rottometer") was especially designed to measure passive knee rotation in vivo. The device had earlier been evaluated with respect to it's validity and reliability. In the present study, we evaluated knee rotation in knee-healthy individuals and studied possible age and gender related differences. Measurements of total internal-external rotation were made at 90 degrees , 60 degrees , and 30 degrees of flexion using 6 and 9 N m torques, as well as the examiner's apprehension of end-feel as displacing forces. The study group constituted of 120 healthy subjects (60 females and 60 males) with no prior or present knee disorders. The sample was divided into four age groups (15-30, 31 45, 46-60, and >60 years). The results showed no differences in knee rotation between the right and left knees or between the different flexion angles. The females showed 10-20% (p < 0.01) larger knee rotation than the males at all the three flexion angles and at all the three applied torques in all age-matched groups. In all age groups in both genders, the internal rotation accounted for 40 44% and the external for 56-60% of the total internal-external knee rotation. PMID- 22778073 TI - Response to 12-0135. PMID- 22778074 TI - Diphenyl diselenide protects against metabolic disorders induced by acephate acute exposure in rats. AB - The present study investigated the effect of diphenyl diselenide [(PhSe)2 ] on metabolic disorders induced by acephate acute exposure in rats. We also investigated a possible mechanism of action of (PhSe)2 against hyperglycemia induced by acephate. (PhSe)2 was administered to rats at a dose of 10 or 30 mg/kg by oral gavage (p.o.) 1 hour prior to acephate administration (140 mg/kg; p.o.). Glucose and corticosterone levels as well as the lipid status were determined in plasma of rats. Cardiovascular risk factors and the atherogenic index were calculated. Glycogen levels as well as tyrosine aminotransferase (TAT) and glucose-6-phosphatase (G6Pase) activities were determined in livers of rats. Cerebral acetylcholinesterase (AChE) activity was assayed. Acephate induced an increase in glucose and corticosterone levels as well as in TAT and G6Pase activities. AChE activity was inhibited by acephate. Triglyceride (TG) levels and the cardiovascular risk factor TG/high-density lipoprotein-cholesterol (HDL) were increased by acephate. (PhSe)2 was effective against the metabolic disorders induced by acephate acute exposure in rats. PMID- 22778075 TI - Spectrophotometric measurements of human tissues for the detection of subjacent blood vessels in an endonasal endoscopic surgical approach. AB - Thin slices of human tissues are characterized concerning reflection and transmission in a wavelength range from 400 to 1700 nm. The results are primarily useful to find a wavelength for the detection of subjacent blood vessels during surgical procedures, especially neurological surgery. The measurements have been conducted using a customized measuring station, utilizing two halogen bulb lamps and two spectrometers. This paper focuses on creating a data base with the optical properties of artery, brain, bone, nasal mucosa, and nerve. The spectral distributions are compared among each other, similarities and differences are pointed out. Each tissue has got unique spectral characteristics, whereas typical absorption bands can be found in the overall tissues, especially hemoglobin and water absorption bands. The reflectivity maxima are typically located in the red or near-infrared. All the transmission maxima are located between 1075 nm and 1100 nm. The measurements have been conducted at the Institute of Anatomy at the University of Leipzig. PMID- 22778076 TI - A large coronary arteriovenous fistula with MRI and angiographic images. PMID- 22778077 TI - Progressive tremors, paresis and a sudden locked-in state. PMID- 22778078 TI - Sagittal synostosis. AB - This report concerns a 20-month-old boy, born at 31 weeks of gestation, being followed in the paediatric clinic because of prematurity. He was developing appropriately for his age and his head circumference was growing steadily (between the 75th and 90th centile), with weight and height on the 25th centile. An x-ray of his skull was performed at this stage because of his head shape, which was long and narrow (scaphocephalic)-in itself suggestive of sagittal synostosis. The x-ray confirmed the diagnosis. He was referred to a regional neurosurgical unit for further management. He had a successful surgical correction without major problems. It is to be emphasised that there is a higher morbidity and mortality if reconstructive surgery is not carried out at an early age, and therefore early diagnosis is vital in this congenital condition. PMID- 22778079 TI - Disseminated intra-abdominal hydatidosis causing acute intestinal obstruction--a rare presentation. AB - Hydatid disease is caused by Echinococcus granulosus-a parasitic infestation commonly affecting the liver. Disseminated intra-abdominal hydatid disease may occur following the rupture of the hydatid cyst into the peritoneal cavity causing secondary echinococcosis. We report a very rare case of disseminated hydatidosis involving various abdominal and pelvic organs and causing intestinal obstruction in a female patient. This unusual presentation produced a diagnostic dilemma. PMID- 22778080 TI - Three dimensional echocardiography of tako-tsubo cardiomyopathy with atrial myxoma. PMID- 22778081 TI - Mediastinal mass. PMID- 22778082 TI - Rhabdomyolysis with acute renal failure triggered by the seasonal flu vaccination in a patient taking simvastatin. AB - A man in his 70s presented with bilateral, painful legs and feeling generally unwell following the seasonal flu vaccination. The patient had a background of B cell lymphoma in partial remission. His current medications included simvastatin. Initial investigations revealed rhabdomyolysis and acute renal failure. He was admitted to critical care for renal replacement treatment. Other causes of rhabdomyolysis were excluded and expert opinion agreed that the most likely cause was the influenza vaccination with the concurrent use of simvastatin. The patient's renal function gradually normalised and after several months the patient has regained full power in his legs. PMID- 22778083 TI - A quantitative proteomic and transcriptomic comparison of human mesenchymal stem cells from bone marrow and umbilical cord vein. AB - Human mesenchymal stem cells (hMSCs) are adult multipotent cells that have high therapeutic potential due to their immunological properties. They can be isolated from several different tissues with bone marrow (BM) being the most common source. Because the isolation procedure is invasive, other tissues such as human umbilical cord vein (UCV) have been considered. However, their interchangeability remains unclear. In the present study, total protein extracts of BM-hMSCs and UCV hMSCs were quantitatively compared using gel-LC-MS/MS. Previous SAGE analysis of the same cells was re-annotated to enable comparison and combination of these two data sets. We observed a more than 63% correlation between proteomic and transcriptomic data. In silico analysis of highly expressed genes in cells of both origins suggests that they can be modulated by microRNA, which can change protein abundance. Our results showed that MSCs from both tissues shared high similarity in metabolic and functional processes relevant to their therapeutic potential, especially in the immune system process, response to stimuli, and processes related to the delivery of the hMSCs to a given tissue, such as migration and adhesion. Hence, our results support the idea that the more accessible UCV could be a potentially less invasive source of MSCs. PMID- 22778084 TI - A 4 year prospective study to determine risk factors for severe community acquired pneumonia in children in southern China. AB - BACKGROUND: Pneumonia is the major cause of death under 5 years. With high CAP numbers in China and growing access to PICUs, factors associated with severe CAP need to be determined to optimize care. OBJECTIVE: To prospectively determine PICU CAP admission features and outcomes. METHODS: A 4 year prospective study of CAP aged 1 month to <14 years admitted to PICU, Children's Hospital Affiliated to Soochow University, China. All were managed in a standard manner. Clinical, laboratory, and imaging findings were collected systematically. All received antibiotics. RESULTS: Eight hundred ten (7%) of 10,836 CAP hospital admissions needed PICU. Seven hundred seven (87%) were enrolled. PICU CAP children were young (76% <= 12 months) and 33% had co-morbid conditions; 21% congenital heart disease.21% required mechanical ventilation. The average length of PICU stay was 5 days (range, 3-27). The case fatality rate was 5.8%. Viruses were detected in 38%, RSV 24%; bacteria in 23%, Streptococcus pneumoniae 7%, Haemophilus influenza b 4%, Mycoplasma 11%. On single factor analysis, PICU admission respiratory rate >70/min, grunting/groaning, head nodding, cyanosis, and anemia were associated with respiratory failure and with fatality. On multivariate analysis only presence of congenital heart disease, Trisomy 21 and immunodeficiency correlated with fatality; not microbe nor PICU findings. CONCLUSIONS: Young age and underlying congenital heart disease were associated factors for PICU support in CAP in China. Early referral if altered sensorium, high respiratory rate, head nodding, grunting and anemia, and universal access to conjugated vaccines may decrease morbidity and mortality. PMID- 22778085 TI - 3D direct laser writing of nano- and microstructured hierarchical gecko-mimicking surfaces. AB - Applying 3D direct laser writing, artificial hierarchical gecko-type structures are designed and fabricated down to nanometer dimensions. In this way, the elastic modulus and the length scale of the gecko's setae are very closely matched. Direct laser writing is a very flexible rapid prototyping method allowing the fabrication of arbitrary nanostructures. Since the parameters of the structures can be easily changed, this technique is perfect for design studies of dry adhesives. Measuring the adhesional forces by atomic force microscopy, the influence of several design parameters like density, aspect ratio, and tip-shape on dry adhesion performance are systematically examined. In this way, it is revealed that hierarchy is favorable for artificial gecko-inspired dry adhesives made of stiff materials on the nanometer scale. PMID- 22778086 TI - Rebuttal: Transcatheter valve in ring procedures may be safety and feasibility procedures in carefully selected patients. PMID- 22778087 TI - The power of negative findings. PMID- 22778088 TI - Managing stuttering beyond the preschool years. AB - PURPOSE: This prologue serves to introduce a research forum composed of studies that address the topic of stuttering in school-age children and adolescents. Researchers are encouraged to continue to build the knowledge base that sustains evidence-based practice in this area. METHOD: The nature of stuttering as it evolves from early childhood into the school years is briefly described. Beyond the preschool years, children are unlikely to spontaneously recover from stuttering, and they often go on to suffer negative consequences, academically and socially, because of their disorder. If they are to overcome or manage their stuttering successfully, school-age children and adolescents require high-quality treatment. Three data-based studies that address the topic of stuttering in school-age children or adolescents are described, the ongoing need for empirical evidence regarding the management of stuttering is emphasized, and several issues relevant to future studies in this area are discussed. CONCLUSION: Progress has occurred in the management of stuttering in school-age children and adolescents. Nevertheless, important questions remain unanswered concerning the most effective techniques and strategies to use in helping students who stutter achieve more fluent and natural-sounding speech in their quest to become more confident and effective communicators. PMID- 22778089 TI - Efficacy of auditory interventions for central auditory processing disorder: a response to Fey et al. (2011). AB - PURPOSE: To provide a commentary on "Auditory Processing Disorder and Auditory/Language Interventions: An Evidence-Based Systematic Review" by Fey et al. (2011). METHOD: Examination of the conclusions drawn by Fey et al. (2011) in the context of the American Academy of Audiology (2010a, 2010b) and American Speech-Language-Hearing Association (2005a, 2005b, 2005c) guidelines for the diagnosis and treatment of auditory processing disorder, the evidence cited therein, and other pertinent published reports. RESULTS: The review provided by Fey et al. (2011) is limited due to the exclusion of pertinent efficacy studies from their analysis, inclusion of studies that did not employ strictly auditory based therapies, and lack of well-defined experimental groups in many of the studies cited. Further, the questions posed by their literature review may not have addressed the efficacy of true auditory interventions in the remediation of auditory difficulties in children who have primary deficits in central auditory processing. CONCLUSION: A more comprehensive review than that done by Fey et al. (2011) would have better addressed the fundamental question of the efficacy of direct remediation activities for children with central auditory processing disorder. PMID- 22778090 TI - Auditory training for children with auditory processing disorder and language impairment: a response to Bellis, Chermak, Weihing, and Musiek. AB - PURPOSE: We respond to Bellis, Chermak, Weihing, and Musiek's (2012) criticisms of the evidence-based systematic review of Fey et al. (2011) on the effects of auditory training on auditory, spoken, and written language performance of children with auditory processing disorder or language impairment. In general, we argue that the conceptualizations and methods on which our review was based were well motivated, and that our original conclusions are valid given the limited evidence that is currently available from clinical studies of auditory training with school-age children with auditory processing disorder or language impairment. PMID- 22778091 TI - Improved solvent formulations for efficient CO2 absorption and low-temperature desorption. AB - This experimental study describes efficient CO2 capture by 2-amino-2-methyl-1 propanol (AMP)/piperazine (PZ) in ethylene glycol monoethyl ether (EGMEE, 2 ethoxyethanol) containing approximately 15 wt % of water. In these experiments, the solvent is continuously circulated between the absorber (packed-bed reactor at 30, 40, or 45 degrees C) and the desorber (at 80, 85, or 90 degrees C). The CO2 -solvent reaction equilibria have been investigated by using 13C NMR spectroscopy, which provides confirmatory evidence that the formation of mono- and biscarbamate derivatives of PZ accounts for most of the CO2 absorbed by the AMP/PZ/EGMEE/H2O blend. The solid-state structures of AMP carbamate and of the carbonate salt of protonated AMP have been determined by using XRD. Both AMPCO2( ) and CO(3)(2-) species completely convert to the monoalkyl carbonates on dissolving the respective salts in methanol, ethanol, or ethylene glycol. PMID- 22778092 TI - FTC scrutiny of health professions regulation. PMID- 22778093 TI - Infection with Mycobacterium avium subsp. paratuberculosis results in rapid interleukin-1beta release and macrophage transepithelial migration. AB - Pathogen processing by the intestinal epithelium involves a dynamic innate immune response initiated by pathogen-epithelial cell cross talk. Interactions between epithelium and Mycobacterium avium subsp. paratuberculosis have not been intensively studied, and it is currently unknown how the bacterium-epithelial cell cross talk contributes to the course of infection. We hypothesized that M. avium subsp. paratuberculosis harnesses host responses to recruit macrophages to the site of infection to ensure its survival and dissemination. We investigated macrophage recruitment in response to M. avium subsp. paratuberculosis using a MAC-T bovine macrophage coculture system. We show that M. avium subsp. paratuberculosis infection led to phagosome acidification within bovine epithelial (MAC-T) cells as early as 10 min, which resulted in upregulation of interleukin-1beta (IL-1beta) at transcript and protein levels. Within 10 min of infection, macrophages were recruited to the apical side of MAC-T cells. Inhibition of phagosome acidification or IL-1beta abrogated this response, while MCP-1/CCL-2 blocking had no effect. IL-1beta processing was dependent upon Ca(2+) uptake from the extracellular medium and intracellular Ca(2+) oscillations, as determined by EGTA and BAPTA-AM [1,2-bis(2-aminophenoxy) ethane-N,N,N',N' tetraacetic acid tetrakis (acetoxymethyl ester)] treatments. Thus, M. avium subsp. paratuberculosis is an opportunist that takes advantage of extracellular Ca(2+)-dependent phagosome acidification and IL-1beta processing in order to efficiently transverse the epithelium and enter its niche--the macrophage. PMID- 22778094 TI - Candida albicans and bacterial microbiota interactions in the cecum during recolonization following broad-spectrum antibiotic therapy. AB - Candida albicans is a normal member of the gastrointestinal (GI) tract microbiota of healthy humans, but during host immunosuppression or alterations in the bacterial microbiota, C. albicans can disseminate and cause life-threatening illness. The bacterial microbiome of the GI tract, including lactic acid bacteria (LAB), plays a vital role in preventing fungal invasion. However, little is known about the role of C. albicans in shaping the bacterial microbiota during antibiotic recovery. We investigated the fungal burdens in the GI tracts of germfree mice and mice with a disturbed microbiome to demonstrate the role of the microbiota in preventing C. albicans colonization. Histological analysis demonstrated that colonization with C. albicans during antibiotic treatment does not trigger overt inflammation in the murine cecum. Bacterial diversity is reduced long term following cefoperazone treatment, but the presence of C. albicans during antibiotic recovery promoted the recovery of bacterial diversity. Cefoperazone diminishes Bacteroidetes populations long term in the ceca of mice, but the presence of C. albicans during cefoperazone recovery promoted Bacteroidetes population recovery. However, the presence of C. albicans resulted in a long-term reduction in Lactobacillus spp. and promoted Enterococcus faecalis populations. Previous studies have focused on the ability of bacteria to alter C. albicans; this study addresses the ability of C. albicans to alter the bacterial microbiota during nonpathogenic colonization. PMID- 22778095 TI - Identification of genes that contribute to the pathogenesis of invasive pneumococcal disease by in vivo transcriptomic analysis. AB - Streptococcus pneumoniae (the pneumococcus) continues to be responsible for a high level of global morbidity and mortality resulting from pneumonia, bacteremia, meningitis, and otitis media. Here we have used a novel technique involving niche-specific, genome-wide in vivo transcriptomic analyses to identify genes upregulated in distinct niches during pathogenesis after intranasal infection of mice with serotype 4 or 6A pneumococci. The analyses yielded 28 common, significantly upregulated genes in the lungs relative to those in the nasopharynx and 25 significantly upregulated genes in the blood relative to those in the lungs in both strains, some of which were previously unrecognized. The role of five upregulated genes from either the lungs or the blood in pneumococcal pathogenesis and virulence was then evaluated by targeted mutagenesis. One of the mutants (DeltamalX) was significantly attenuated for virulence in the lungs, two (DeltaaliA and DeltailvH) were significantly attenuated for virulence in the blood relative to the wild type, and two others (DeltacbiO and DeltapiuA) were completely avirulent in a mouse intranasal challenge model. We also show that the products of aliA, malX, and piuA are promising candidates for incorporation into multicomponent protein-based pneumococcal vaccines currently under development. Importantly, we suggest that this new approach is a viable complement to existing strategies for the discovery of genes critical to the distinct stages of invasive pneumococcal disease and potentially has broad application for novel protein antigen discovery in other pathogens such as S. pyogenes, Haemophilus influenzae type b, and Neisseria meningitidis. PMID- 22778096 TI - Role of RelA and SpoT in Burkholderia pseudomallei virulence and immunity. AB - Burkholderia pseudomallei is a Gram-negative soil bacterium and the causative agent of melioidosis, a disease of humans and animals. It is also listed as a category B bioterrorism threat agent by the U.S. Centers for Disease Control and Prevention, and there is currently no melioidosis vaccine available. Small modified nucleotides such as the hyperphosphorylated guanosine molecules ppGpp and pppGpp play an important role as signaling molecules in prokaryotes. They mediate a global stress response under starvation conditions and have been implicated in the regulation of virulence and survival factors in many bacterial species. In this study, we created a relA spoT double mutant in B. pseudomallei strain K96243, which lacks (p)ppGpp-synthesizing enzymes, and investigated its phenotype in vitro and in vivo. The B. pseudomallei DeltarelA DeltaspoT mutant displayed a defect in stationary-phase survival and intracellular replication in murine macrophages. Moreover, the mutant was attenuated in the Galleria mellonella insect model and in both acute and chronic mouse models of melioidosis. Vaccination of mice with the DeltarelA DeltaspoT mutant resulted in partial protection against infection with wild-type B. pseudomallei. In summary, (p)ppGpp signaling appears to represent an essential component of the regulatory network governing virulence gene expression and stress adaptation in B. pseudomallei, and the DeltarelA DeltaspoT mutant may be a promising live attenuated vaccine candidate. PMID- 22778097 TI - The Toxoplasma gondii peptide AS15 elicits CD4 T cells that can control parasite burden. AB - The apicomplexan parasite Toxoplasma gondii can cause severe disease in immunocompromised individuals. Previous studies in mice have focused largely on CD8(+) T cells, and the role of CD4 T cells is relatively unexplored. Here, we show that immunization of the C57BL/6 strain of mice, in which the immunodominant CD8 T cell response to the parasite dense-granule protein GRA6 cannot be generated, leads to a prominent CD4 T cell response. To identify the CD4 T cell stimulating antigens, we generated a T. gondii-specific, lacZ-inducible, CD4 T cell hybridoma and used it as a probe to screen a T. gondii cDNA library. We isolated a cDNA encoding a protein of unknown function that we call CD4Ag28m and identified the minimal peptide, AS15, which was presented by major histocompatibility complex (MHC) class II molecules to the CD4 T cells. Immunization of mice with the AS15 peptide provided significant protection against subsequent parasite challenge, resulting in a lower parasite burden in the brain. Our findings identify the first CD4 T cell-stimulating peptide that can confer protection against toxoplasmosis and provide an important tool for the study of CD4 T cell responses and the design of effective vaccines against the parasite. PMID- 22778098 TI - Campylobacter jejuni translocation across intestinal epithelial cells is facilitated by ganglioside-like lipooligosaccharide structures. AB - Translocation across intestinal epithelial cells is an established pathogenic feature of the zoonotic bacterial species Campylobacter jejuni. The number of C. jejuni virulence factors known to be involved in translocation is limited. In the present study, we investigated whether sialylation of C. jejuni lipooligosaccharide (LOS) structures, generating human nerve ganglioside mimics, is important for intestinal epithelial translocation. We here show that C. jejuni isolates expressing ganglioside-like LOS bound in larger numbers to the Caco-2 intestinal epithelial cells than C. jejuni isolates lacking such structures. Next, we found that ganglioside-like LOS facilitated endocytosis of bacteria into Caco-2 cells, as visualized by quantitative microscopy using the early and late endosomal markers early endosome-associated protein 1 (EEA1), Rab5, and lysosome associated membrane protein 1 (LAMP-1). This increased endocytosis was associated with larger numbers of surviving and translocating bacteria. Next, we found that two different intestinal epithelial cell lines (Caco-2 and T84) responded with an elevated secretion of the T-cell attractant CXCL10 to infection by ganglioside like LOS-expressing C. jejuni isolates. We conclude that C. jejuni translocation across Caco-2 cells is facilitated by ganglioside-like LOS, which is of clinical relevance since C. jejuni ganglioside-like LOS-expressing isolates are linked with severe gastroenteritis and bloody stools in C. jejuni-infected patients. PMID- 22778099 TI - FimA, FimF, and FimH are necessary for assembly of type 1 fimbriae on Salmonella enterica serovar Typhimurium. AB - Salmonella enterica serovar Typhimurium is a Gram-negative member of the family Enterobacteriaceae and is a common cause of bacterial food poisoning in humans. The fimbrial appendages are found on the surface of many enteric bacteria and enable the bacteria to bind to eukaryotic cells. S. Typhimurium type 1 fimbriae are characterized by mannose-sensitive hemagglutination and are assembled via the chaperone/usher pathway. S. Typhimurium type 1 fimbrial proteins are encoded by the fim gene cluster (fimAICDHFZYW), with fimAICDHF expressed as a single transcriptional unit. The structural components of the fimbriae are FimA (major subunit), FimI, FimH (adhesin), and FimF (adaptor). In order to determine which components are required for fimbrial formation in S. Typhimurium, mutations in fimA, fimI, fimH, and fimF were constructed and examined for their ability to produce surface-assembled fimbriae. S. Typhimurium SL1344DeltafimA, -DeltafimH, and -DeltafimF mutants were unable to assemble fimbriae, indicating that these genes are necessary for fimbrial production in S. Typhimurium. However, SL1344DeltafimI was able to assemble fimbriae. In Escherichia coli type 1 and Pap fimbriae, at least two adaptors are expressed in addition to the adhesins. However, E. coli type 1 and Pap fimbriae have been reported to be able to assemble fimbriae in the absence of these proteins. These results suggest differences between the S. Typhimurium type 1 fimbrial system and the E. coli type 1 and Pap fimbrial systems. PMID- 22778100 TI - The meningococcal minor pilin PilX is responsible for type IV pilus conformational changes associated with signaling to endothelial cells. AB - Neisseria meningitidis crosses the blood-brain barrier (BBB) following the activation of the beta2-adrenergic receptor by the type IV pili (TFP). Two components of the type IV pili recruit the beta2-adrenergic receptor, the major pilin PilE and the minor pilin PilV. Here, we report that a strain deleted of PilX, one of the three minor pilins, is defective in endothelial cell signaling. The signaling role of PilX was abolished when pili were not retractable. Purified PilX was unable to recruit the beta2-adrenergic receptor, thus suggesting that PilX was playing an indirect role in endothelial cell signaling. Considering the recent finding that type IV pili can transition into a new conformation (N. Biais, D. L. Higashi, J. Brujic, M. So, and M. P. Sheetz, Proc. Natl. Acad. Sci. U. S. A. 107:11358-11363, 2010), we hypothesized that PilX was responsible for a structural modification of the fiber and allowed hidden epitopes to be exposed. To confirm this hypothesis, we showed that a monoclonal antibody which recognizes a linear epitope of PilE bound fibers only when bacteria adhered to endothelial cells. On the other hand, this effect was not observed in PilX-deleted pili. A deletion of a region of PilX exposed on the surface of the fiber had phenotypical consequences identical to those of a PilX deletion. These data support a model in which surface-exposed motifs of PilX use forces generated by pilus retraction to promote conformational changes required for TFP-mediated signaling. PMID- 22778101 TI - Diarrhea and colitis in mice require the Salmonella pathogenicity island 2 encoded secretion function but not SifA or Spv effectors. AB - We investigated the roles of Salmonella pathogenicity island 2 (SPI-2) and two SPI-2 effectors in Salmonella colitis and diarrhea in genetically resistant BALB/c.D2(Slc11a1) congenic mice with the wild-type Nramp1 locus. Wild-type Salmonella enterica serovar Typhimurium 14028s caused a pan-colitis, and the infected mice developed frank diarrhea with a doubling of the fecal water content. An ssaV mutant caused only a 26% increase in fecal water content, without producing the pathological changes of colitis, and it did not cause weight loss over a 1-week period of observation. However, two SPI-2 effector mutants, the spvB and sifA mutants, and a double spvB sifA mutant caused diarrhea and colitis, even though the sifA mutant was sensitive to killing by bone marrow derived macrophages from BALB/c.D2 mice and was severely impaired in extraintestinal growth but not in growth in the cecum. These results demonstrate that systemic S. enterica infection and diarrhea/colitis are distinct pathogenic processes and that only the former requires spvB and sifA. PMID- 22778102 TI - HcpR of Porphyromonas gingivalis is required for growth under nitrosative stress and survival within host cells. AB - Although the Gram-negative, anaerobic periodontopathogen Porphyromonas gingivalis must withstand nitrosative stress, which is particularly high in the oral cavity, the mechanisms allowing for protection against such stress are not known in this organism. In this study, microarray analysis of P. gingivalis transcriptional response to nitrite and nitric oxide showed drastic upregulation of the PG0893 gene coding for hybrid cluster protein (Hcp), which is a putative hydroxylamine reductase. Although regulation of hcp has been shown to be OxyR dependent in Escherichia coli, here we show that in P. gingivalis its expression is dependent on the Fnr-like regulator designated HcpR. Growth of the isogenic mutant V2807, containing an ermF-ermAM insertion within the hcpR (PG1053) gene, was significantly reduced in the presence of nitrite (P < 0.002) and nitric oxide generating nitrosoglutathione (GSNO) (P < 0.001), compared to that of the wild type W83 strain. Furthermore, the upregulation of PG0893 (hcp) was abrogated in V2807 exposed to nitrosative stress. In addition, recombinant HcpR bound DNA containing the hcp promoter sequence, and the binding was hemin dependent. Finally, V2807 was not able to survive with host cells, demonstrating that HcpR plays an important role in P. gingivalis virulence. This work gives insight into the molecular mechanisms of protection against nitrosative stress in P. gingivalis and shows that the regulatory mechanisms differ from those in E. coli. PMID- 22778103 TI - Polyclonal mucosa-associated invariant T cells have unique innate functions in bacterial infection. AB - Mucosa-associated invariant T (MAIT) cells are a unique population of alphabeta T cells in mammals that reside preferentially in mucosal tissues and express an invariant Valpha paired with limited Vbeta T-cell receptor (TCR) chains. Furthermore, MAIT cell development is dependent upon the expression of the evolutionarily conserved major histocompatibility complex (MHC) class Ib molecule MR1. Using in vitro assays, recent studies have shown that mouse and human MAIT cells are activated by antigen-presenting cells (APCs) infected with diverse microbes, including numerous bacterial strains and yeasts, but not viral pathogens. However, whether MAIT cells play an important, and perhaps unique, role in controlling microbial infection has remained unclear. To probe MAIT cell function, we show here that purified polyclonal MAIT cells potently inhibit intracellular bacterial growth of Mycobacterium bovis BCG in macrophages (MPhi) in coculture assays, and this inhibitory activity was dependent upon MAIT cell selection by MR1, secretion of gamma interferon (IFN-gamma), and an innate interleukin 12 (IL-12) signal from infected MPhi. Surprisingly, however, the cognate recognition of MR1 by MAIT cells on the infected MPhi was found to play only a minor role in MAIT cell effector function. We also report that MAIT cell deficient mice had higher bacterial loads at early times after infection compared to wild-type (WT) mice, demonstrating that MAIT cells play a unique role among innate lymphocytes in protective immunity against bacterial infection. PMID- 22778104 TI - Natural history of inhalation melioidosis in rhesus macaques (Macaca mulatta) and African green monkeys (Chlorocebus aethiops). AB - Burkholderia pseudomallei, the causative agent of melioidosis, is recognized as a serious health threat due to its involvement in septic and pulmonary infections in areas of endemicity and is recognized by the Centers for Disease Control and Prevention as a category B biothreat agent. An animal model is desirable to evaluate the pathogenesis of melioidosis and medical countermeasures. A model system that represents human melioidosis infections is essential in this process. A group of 10 rhesus macaques (RMs) and 10 African green monkeys (AGMs) was exposed to aerosolized B. pseudomallei 1026b. The first clinical signs were fever developing 24 to 40 h postexposure followed by leukocytosis resulting from a high percentage of neutrophils. Dyspnea manifested 2 to 4 days postexposure. In the AGMs, an increase in interleukin 1beta (IL-1beta), IL-6, IL-8, gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) was observed. In the RMs, IL-1beta, IL-6, and TNF-alpha increased. All the RMs and AGMs had various degrees of bronchopneumonia, with inflammation consisting of numerous neutrophils and a moderate number of macrophages. Both the RMs and the AGMs appear to develop a melioidosis infection that closely resembles that seen in acute human melioidosis. However, for an evaluation of medical countermeasures, AGMs appear to be a more appropriate model. PMID- 22778105 TI - Glycogenic acanthosis presenting as leukoplakia on the tongue. AB - This report describes a rare case of glycogenic acanthosis (GA) located on the tongue of a 72-year-old man. The patient presented with a white plaque that had been on the right side of the tongue for 5 years. Histologically, the lesion was characterised by thickened squamous epithelium with abundant intracellular glycogen deposits. No epithelial dysplasia was noted. This is the first report of GA involving the tongue. This benign condition should be added to the large number of lesions responsible for leukoplakia in this anatomical location. PMID- 22778106 TI - Displaced stress fracture of the femoral neck in young active adults. AB - Stress fractures of the femoral neck in healthy individuals are rare and most prevalent among long-distance runners and military recruits. Women seem to be at higher risk of developing stress fractures because of possible eating disorders and, thereby, following amenorrhoea and osteoporosis. The majority of fractures of the femoral neck are undisplaced. However, they might progress into displaced fractures with avascular necrosis of the femoral head and following development of osteoarthritis as a probable consequence even when treated properly. Early diagnosis with MRI or radionuclide scanning in patients with a history of pain in the groin region during training might be crucial in detecting the fractures at early stages; thereby preventing possible complications following surgical treatment of displaced fractures. The authors present a report of two young adults who developed displaced fractures of the femoral neck and were treated with closed reduction and internal fixation. PMID- 22778107 TI - Paradoxical bradycardia in a patient with haemorrhagic shock secondary to blunt abdominal trauma. AB - A 47-year-old woman, with no previous medical problems, presented to the Accident and Emergency department with left shoulder pain following a fall onto her left side from a horse. Physical examination was unremarkable and she was discharged with simple analgesia. However, 2 h later, she re-presented with worsening left shoulder pain, dizziness and mild epigastric discomfort. A new examination revealed blood pressure of 100/60 mm Hg, which dropped to 95/65 mm Hg on standing, a Glasgow Coma Scale score of 15 and pulse of 62 beats/min. She was resuscitated with 2 litres of Hartmann's fluid. A focused assessment with sonography for trauma (FAST) scan of her abdomen was negative. Then, 1 h later she experienced generalised abdominal pain and developed postural hypotension. However she remained bradycardic (heart rate 45-60 beats/min). Repeat examination revealed peritonitis. A further FAST scan showed free fluid in the left hypochondrium. A CT scan demonstrated a complex tear of the spleen, for which she underwent an emergency total splenectomy. Her postoperative recovery was uncomplicated. PMID- 22778108 TI - Aberrant right subclavian artery and right-sided ductus arteriosus. PMID- 22778109 TI - Hypophosphataemia-inducing mesenchymal tumour in the foot. AB - Tumour-induced (or oncogenic) osteomalacia is a paraneoplastic syndrome characterised by progressive fatigue, muscle weakness, bone pain, non-healing and recurrent fractures caused by mesenchymal tumours that secrete proteins that inhibit renal phosphate transport and 1alpha-hydroxylation of 25-OH-vitamin D. The potentially curative treatment of choice is complete surgical excision of the tumour. PMID- 22778110 TI - Dialysis access pseudoaneurysm: endovascular treatment with a covered stent. AB - Iatrogenic pseudoaneurysms of the brachial artery are rare complications of haemodialysis access procedures and can lead to substantial morbidity and mortality if not managed promptly; however, surgery is also associated with the potential risk of severe complications. We describe the clinical and radiological findings relating to a dialysed patient who developed a huge iatrogenic pseudoaneurysm of the brachial artery (due to an inadvertent artery puncture), which was successfully treated by means of the percutaneous implantation of a polytetrafluoroethylene (PTFE)-covered stent. PMID- 22778111 TI - Patent vitellointestinal duct. AB - During the 3rd week of intrauterine life there is a communication between the intraembryonic gut and the yolk sac. As the development proceeds this communication narrows into a tube known as the vitellointestinal duct (VID). With the establishment of placental nutrition this duct usually becomes obliterated by the end of the 7th week of intrauterine life. In about 2% of humans this duct persists and gives rise to a group of anomalies of which Meckel's diverticulum is the commonest and complete patency of the duct is the rarest.1 We report a case of a 4-month-old infant who presented with umbilical polyp, discharge from the umbilicus, significant dehydration and failure to thrive because of complete patency of the VID. PMID- 22778113 TI - Histomorphological and ultrastructural changes of the placenta in mice exposed to formaldehyde. AB - Formaldehyde (FA) is widely used in industrial and medical settings. It has long been suspected of causing adverse reproductive and developmental effects. However, the effects of exposure to FA on the reproduction are still a matter of scientific controversy. In this study, we evaluate the hypothesis that adverse developmental outcomes of the exposure to FA might be due to its effects on the placental structure. So, histological changes of the placenta in the mice exposed to FA gas were assessed at light and electron microscopy levels. A total of 40 pregnant Balb/C mice were randomly allotted to four groups in which the animals were exposed to FA at the doses of 0 (control), 7, 14 and 28 ppm, respectively, by inhalation, consecutively, for 8 h/d during the organogenesis period. On day 17 of gestation, the animals were killed and the histological specimens of the placentas were taken for light and electron microscopy studies. Also, morphological parameters of the placentas were measured manually. The results showed that the effects of FA on the placenta are not dose dependent. In the FA exposed mice, an increase in the number and size of trophoblastic giant cells and an enlargement of spongiotrophoblastic cells in the basal zone of placenta were seen. Also, a significant increase in placental weight as well as the ratio of placental to fetal weight but a decrease in the fetal weight were found in the treated groups when compared with those in the control mice (p < 0.05). Moreover, ultrastructural results demonstrated that the diameter of labyrinth interhemal membrane as well as the thickness of trophoblastic basement membranes were significantly increased in the FA-exposed mice. In addition, in the FA-treated animals, a severe accumulation of cytoplasmic droplets in the II and III trophoblastic layers of the placenta were seen. In conclusion, this study may suggest that the exposure to FA during the organogenesis period at doses of 7-28 ppm induces toxic changes in the placental structure. These changes disrupt placental functions and leads to a decrease in the fetal weight. PMID- 22778112 TI - Protective effects of aqueous extract of Hammada scoparia against hepatotoxicity induced by ethanol in the rat. AB - Aqueous extract (AE) of Hammada scoparia leaves was chemically characterized and its hepatoprotective activities were investigated in vivo in rat model. Wistar rats were treated daily with 35% ethanol solution (3 g/kg/day) during 4 weeks and fed with basal diet or basal diet containing AE (200 mg/kg/day). Control rats were treated with saline solution and fed with basal diet. The bioactivity of AE against ethanol-induced oxidative stress in rat liver was studied in order to explore its hepatoprotective effects. H. scoparia extract used at 200 mg/kg body weight significantly prevented the effects of ethanol, which induced a hepatic pathological damage and increased the levels of the serum markers of the enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Concomitantly, with these changes, this extract also prevented ethanol-induced oxidative stress in the rat liver as evidenced by the decreased lipid peroxidation level, a considerable decrease in the activities of AST, ALT and ALP and restoring the activities of antioxidant enzymes: superoxide dismutase, catalase and glutathione peroxidase. These biochemical changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the AE of H. scoparia. PMID- 22778114 TI - Effects of diets containing genistein and diadzein in a long-term study on sex steroid dynamics of goldfish (Carassius auratus). AB - The effect of long-term exposure of goldfish to dietary genistein and diadzein on the concentrations of plasma sex steroids (testosterone (T), 17beta-estradiol (E2)) and the gonadosomatic index (GSI) was assessed. The study was conducted on four groups for a period of 2 years, from the age of 20 weeks to first spawning. Four doses of genistein and diadzein were applied in the feed: genistein: 0 ug/g, diadzein: 0 ug/g (control group); genistein: 24.26 ug/g, diadzein: 21.7 ug/g (diet 1); genistein: 51.55 ug/g, diadzein: 46.13 ug/g (diet 2); and genistein: 75.83 ug/g, diadzein: 67.82 ug/g (diet 3). Throughout the experiment, there were no significant dose- or time-related effects of genistein and diadzein contents on the T level in both sexes. Furthermore, at the highest genistein and diadzein contents, there was an elevating plasma concentration of E2 at all sampling points (p < 0.05) and a time-related effect occurred (p < 0.05). Although the E2 concentrations in the plasma of female, throughout the experiment, were higher than in males, at the last sampling, the plasma concentrations of E2 reduced among females and became lower than that in males. The effects of isoflavone content were found on GSI of females at the fourth and fifth sampling among the treatments. Isoflavone contents also affect GSI of males at the second, fourth and the last sampling. Our findings suggest that overall genistein and diadzein exposure in early life stages can cause alterations in the reproductive organs and influence sex steroidogenesis. PMID- 22778115 TI - Hepatoprotective potential of astaxanthin against 2,3,7,8-tetrachlorodibenzo-p dioxin in cultured rat hepatocytes. AB - The purpose of this study was to evaluate the effect of carotenoid astaxanthin (ASTA) on cultured primary rat hepatocytes treated with 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) on the cell viability (3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyl tetrazolium bromide, MTT), lactate dehydrogenase (LDH) activity, 8-oxo-2-deoxyguanosine (8-OH-dG), total antioxidant capacity (TAC), and total oxidative stress (TOS) levels, and liver micronucleus rates. ASTA (2.5, 5, and 10 uM) was added to cultures alone or simultaneously with TCDD (5 and 10 uM) for 48 h. The results of MTT and LDH assays showed that both doses of TCDD caused significant decrease in cell viability. Also, TCDD significantly increased TOS and decreased TAC level in rat hepatocytes. On the basis of increasing doses, the dioxin caused significant increase in micronucleated hepatocytes) and 8-OH-dG level as compared to control culture. The presence of ASTA with TCDD minimized its effects on primary hepatocytes cultures and DNA damages. PMID- 22778116 TI - Opioids for chronic pain: first do no harm. PMID- 22778117 TI - Opioids for chronic noncancer pain: as the pendulum swings, who should set prescribing standards for primary care? PMID- 22778118 TI - Depression and prescription opioid misuse among chronic opioid therapy recipients with no history of substance abuse. AB - PURPOSE: Opioid misuse in the context of chronic opioid therapy (COT) is a growing concern. Depression may be a risk factor for opioid misuse, but it has been difficult to tease out the contribution of co-occurring substance abuse. This study aims to examine whether there is an association between depression and opioid misuse in patients receiving COT who have no history of substance abuse. METHODS: A telephone survey was conducted at Group Health Cooperative and Kaiser Permanente of Northern California. We interviewed 1,334 patients on COT for noncancer pain who had no history of substance abuse. Patients were asked about 3 forms of opioid misuse: (1) self-medicating for symptoms other than pain, (2) self-increasing doses, and (3) giving to or getting opioids from others. Depression was evaluated by the 8-item Patient Health Questionnaire (PHQ-8). RESULTS: Compared with patients who were not depressed (PHQ-8 score 0 to 4), patients with moderate depression (PHQ-8 score 10 to 14) and severe depression (PHQ-8 score 15 or higher) were 1.8 and 2.4 times more likely, respectively, to misuse their opioid medications for non-pain symptoms. Patients with mild (PHQ-8 score 5 to 9), moderate, and severe depression were 1.9, 2.9, and 3.1 times more likely, respectively, to misuse their opioid medications by self-increasing their dose. There was no statistically significant association between depression and giving opioids to or getting them from others. CONCLUSION: In patients with no substance abuse history, depressive symptoms are associated with increased rates of some forms of self-reported opioid misuse. Clinicians should be alert to the risk of patients with depressive symptoms using opioids to relieve these symptoms and thereby using more opioids than prescribed. PMID- 22778119 TI - Interactive preventive health record to enhance delivery of recommended care: a randomized trial. AB - PURPOSE: Americans receive only one-half of recommended preventive services. Information technologies have been advocated to engage patients. We tested the effectiveness of an interactive preventive health record (IPHR) that links patients to their clinician's record, explains information in lay language, displays tailored recommendations and educational resources, and generates reminders. METHODS: This randomized controlled trial involved 8 primary care practices. Four thousand five hundred patients were randomly selected to receive a mailed invitation to use the IPHR or usual care. Outcomes were measured using patient surveys and electronic medical record data and included IPHR use and service delivery. Comparisons were made between invited and usual-care patients and between users and nonusers among those invited to use the IPHR. RESULTS: At 4 and 16 months, 229 (10.2%) and 378 (16.8%) of invited patients used the IPHR. The proportion of patients up-to-date with all services increased between baseline and 16 months by 3.8% among intervention patients (from 11.4% to 15.2%, P <.001) and by 1.5% among control patients (from 11.1% to 12.6%, P = .07), a difference of 2.3% (P = .05). Greater increases were observed among patients who used the IPHR. At 16 months, 25.1% of users were up-to-date with all services, double the rate among nonusers. At 4 months, delivery of colorectal, breast, and cervical cancer screening increased by 19%, 15%, and 13%, respectively, among users. CONCLUSIONS: Information systems that feature patient-centered functionality, such as the IPHR, have potential to increase preventive service delivery. Engaging more patients to use systems could have important public health benefits. PMID- 22778120 TI - TRIPPD: a practice-based network effectiveness study of postpartum depression screening and management. AB - PURPOSE: Postpartum depression is common but inadequately recognized and undertreated. Continuing depressive symptoms are associated with adverse outcomes for the woman, her infant, and family. We wanted to determine the effect of a practice-based training program for screening, diagnosis, and management of depression in postpartum mothers. METHODS: In this practice-based effectiveness study, 28 practices were randomized to usual care (n = 14) or intervention (n = 14), and 2,343 women were enrolled between 5 and 12 weeks' postpartum. The intervention sites received education and tools for postpartum depression screening, diagnosis, initiation of therapy, and follow-up within their practices. Usual-care practices received a 30-minute presentation about postpartum depression. Screening information for the usual care was obtained from baseline surveys sent directly to the central site but was not available for patient care. Outcomes were based on patient-reported outcomes (level of depressive symptoms) from surveys at 6 and 12 months, plus medical record review (diagnosis and therapy initiation). RESULTS: Among the 2,343 women enrolled, 1,897 (80.1%) provided outcome information, and were included in the analysis. Overall, 654 (34.5% of 1,897) women had elevated screening scores indicative of depression, with comparable rates in the intervention and usual-care groups. Among the 654 women with elevated postpartum depression screening scores, those in the intervention practices were more likely to receive a diagnosis (P = .0006) and therapy for postpartum depression (P = .002). They also had lower depressive symptom levels at 6 (P = .07) and 12 months' (P=.001) postpartum. CONCLUSIONS: Primary care-based screening, diagnosis, and management improved mother's depression outcomes at 12 months. This practical approach could be implemented widely with modest resources. PMID- 22778121 TI - How family physicians address diagnosis and management of depression in palliative care patients. AB - PURPOSE: Depression is highly prevalent in palliative care patients. In clinical practice, there is concern about both insufficient and excessive diagnosis and treatment of depression. In the Netherlands, family physicians have a central role in delivering palliative care. We explored variation in family physicians' opinions regarding the recognition, diagnosis, and management of depression in palliative care patients. METHODS: We conducted a focus group study in a sample of family physicians with varied practice locations and varying expertise in palliative care. Transcripts were analyzed independently by 2 researchers using constant comparative analysis in ATLAS.ti. RESULTS: In 4 focus group discussions with 22 family physicians, the physicians described the diagnostic and therapeutic process for depression in palliative care patients as a continuous and overlapping process. Differentiating between normal and abnormal sadness was viewed as challenging. The physicians did not strictly apply criteria of depressive disorder but rather relied on their clinical judgment and strongly considered patients' context and background factors. They indicated that managing depression in palliative care patients is mainly supportive and nonspecific. Antidepressant drugs were seldom prescribed. The physicians described difficulties in diagnosing and treating depression in palliative care, and gave suggestions to improve management of depression in palliative care patients in primary care. CONCLUSIONS: Family physicians perceive the diagnosis and management of depression in palliative care patients as challenging. They rely on open communication and a long-standing physician-patient relationship in which the patient's context is of great importance. This approach fits with the patient centered care that is promoted in primary care. PMID- 22778122 TI - Meditation or exercise for preventing acute respiratory infection: a randomized controlled trial. AB - PURPOSE: This study was designed to evaluate potential preventive effects of meditation or exercise on incidence, duration, and severity of acute respiratory infection (ARI) illness. METHODS: Community-recruited adults aged 50 years and older were randomized to 1 of 3 study groups: 8-week training in mindfulness meditation, matched 8-week training in moderate-intensity sustained exercise, or observational control. The primary outcome was area-under-the-curve global illness severity during a single cold and influenza season, using the Wisconsin Upper Respiratory Symptom Survey (WURSS-24) to assess severity. Health care visits and days of missed work were counted. Nasal wash collected during ARI illness was assayed for neutrophils, interleukin-8, and viral nucleic acid. RESULTS: Of 154 adults randomized into the study, 149 completed the trial (82% female, 94% white, mean age 59.3 +/- 6.6 years). There were 27 ARI episodes and 257 days of ARI illness in the meditation group (n = 51), 26 episodes and 241 illness days in the exercise group (n = 47), and 40 episodes and 453 days in the control group (n = 51). Mean global severity was 144 for meditation, 248 for exercise, and 358 for control. Compared with control, global severity was significantly lower for meditation (P = .004). Both global severity and total days of illness (duration) trended toward being lower for the exercise group (P=.16 and P=.032, respectively), as did illness duration for the meditation group (P=.034). Adjusting for covariates using zero-inflated multivariate regression models gave similar results. There were 67 ARI-related days of-work missed in the control group, 32 in the exercise group (P = .041), and 16 in the meditation group (P <.001). Health care visits did not differ significantly. Viruses were identified in 54% of samples from meditation, 42% from exercise, and 54% from control groups. Neutrophil count and interleukin-8 levels were similar among intervention groups. CONCLUSIONS: Training in meditation or exercise may be effective in reducing ARI illness burden. PMID- 22778123 TI - A randomized trial to reduce the prevalence of depression and self-harm behavior in older primary care patients. AB - PURPOSE: We wanted to determine whether an educational intervention targeting general practitioners reduces the 2-year prevalence of depression and self-harm behavior among their older patients. METHODS: Our study was a cluster randomized controlled trial conducted between July 2005 and June 2008. We recruited 373 Australian general practitioners and 21,762 of their patients aged 60 years or older. The intervention consisted of a practice audit with personalized automated audit feedback, printed educational material, and 6 monthly educational newsletters delivered over a period of 2 years. Control physicians completed a practice audit but did not receive individualized feedback. They also received 6 monthly newsletters describing the progress of the study, but they were not offered access to the educational material about screening, diagnosis and management of depression, and suicide behavior in later life. The primary outcome was a composite measure of clinically significant depression (Patient Health Questionnaire score >=10) or self-harm behavior (suicide thoughts or attempt during the previous 12 months). Information about the outcomes of interest was collected at the baseline assessment and again after 12 and 24 months. We used logistic regression models to estimate the effect of the intervention in a complete case analysis and intention-to-treat analysis by imputed chain equations (primary analysis). RESULTS: Older adults treated by general practitioners assigned to the intervention experienced a 10% (95% CI, 3%-17%) reduction in the odds of depression or self-harm behavior during follow-up compared with older adults treated by control physicians. Post hoc analyses showed that the relative effect of the intervention on depression was not significant (OR = 0.93; 95% CI, 0.83-1.03), but its impact on self-harm behavior over 24 months was (OR = 0.80; 95% CI, 0.68-0.94). The beneficial effect of the intervention was primarily due to the relative reduction of self-harm behavior among older adults who did not report symptoms at baseline. The intervention had no obvious effect in reducing the 24-month prevalence of depression or self-harm behavior in older adults who had symptoms at baseline. CONCLUSIONS: Practice audit and targeted education of general practitioners reduced the 2-year prevalence of depression and self-harm behavior by 10% compared with control physicians. The intervention had no effect on recovery from depression or self-harm behavior, but it prevented the onset of new cases of self-harm behavior during follow-up. Replication of these results is required before we can confidently recommend the roll-out of such a program into normal clinical practice. PMID- 22778125 TI - Objective evidence of severe disease: opioid use in chronic pain. AB - Treating chronic pain presents numerous challenges. First, assessing patients with chronic pain is complicated by the lack of objective measures of pain itself. Chronic pain guidelines already developed by national organizations rely on careful history taking rather than objective measures. Second, opioids are an accepted element of chronic pain management, but their use is tempered by risks of overdose, dependency, and the potential for diversion. This essay proposes a new standard for the use of long-term opioids for chronic pain: the presence or absence of objective evidence of severe disease. This standard, which supports responsible prescribing of opioids, is one that clinicians can understand and apply when considering prescribing long-term opioids for chronic pain. Until we have measures of pain itself, we should insist upon objective evidence of severe disease before prescribing opioids for chronic pain. PMID- 22778124 TI - Chemical intolerance in primary care settings: prevalence, comorbidity, and outcomes. AB - PURPOSE: This study extends previous community-based studies on the prevalence and clinical characteristics of chemical intolerance in a sample of primary care clinic patients. We evaluated comorbid medical and psychiatric disorders, functional status, and rates of health care use. METHODS: A total of 400 patients were recruited from 2 family medicine clinic waiting rooms in San Antonio, Texas. Patients completed the validated Quick Environmental Exposure and Sensitivity Inventory (QEESI) to assess chemical intolerance; the Primary Care Evaluation of Mental Disorders (PRIME-MD) screen for possible psychiatric disorders; the Dartmouth-Northern New England Primary Care Cooperative Information Project (Dartmouth COOP) charts for functional status; and the Healthcare Utilization Questionnaire. RESULTS: Overall, 20.3% of the sample met criteria for chemical intolerance. The chemically intolerant group reported significantly higher rates of comorbid allergies and more often met screening criteria for possible major depressive disorder, panic disorder, generalized anxiety disorder, and alcohol abuse disorder, as well as somatization disorder. The total number of possible mental disorders was correlated with chemical intolerance scores (P <.001). Controlling for demographics, patients with chemical intolerance were significantly more likely to have poorer functional status, with trends toward increased medical service use when compared with non-chemically intolerant patients. After controlling for comorbid psychiatric conditions, the groups differed significantly only regarding limitations of social activities. CONCLUSIONS: Chemical intolerance occurs in 1 of 5 primary care patients yet is rarely diagnosed by busy practitioners. Psychiatric comorbidities contribute to functional limitations and increased health care use. Chemical intolerance offers an etiologic explanation. Symptoms may resolve or improve with the avoidance of salient chemical, dietary (including caffeine and alcohol), and drug triggers. Given greater medication intolerances in chemical intolerance, primary care clinicians could use the QEESI to identify patients for appropriate triage to comprehensive nonpharmacologic care. PMID- 22778126 TI - STFM launches programs and services for residency programs. PMID- 22778127 TI - ADFM's fellowship program. PMID- 22778128 TI - The NRMP: all-in...and testing the soapy waters? PMID- 22778129 TI - Encouraging participation of minorities in research studies. PMID- 22778130 TI - AAFP participates in campaign to cut unnecessary medical interventions. PMID- 22778131 TI - ABFM's heart failure self-assessment module simulation actions vis-a-vis guideline recommendations. PMID- 22778132 TI - Multiple roles for the Ess1 prolyl isomerase in the RNA polymerase II transcription cycle. AB - The Ess1 prolyl isomerase in Saccharomyces cerevisiae regulates RNA polymerase II (pol II) by isomerizing peptide bonds within the pol II carboxy-terminal domain (CTD) heptapeptide repeat (YSPTSPS). Ess1 preferentially targets the Ser5-Pro6 bond when Ser5 is phosphorylated. Conformational changes in the CTD induced by Ess1 control the recruitment of essential cofactors to the pol II complex and may facilitate the ordered transition between initiation, elongation, termination, and RNA processing. Here, we show that Ess1 associates with the phospho-Ser5 form of polymerase in vivo, is present along the entire length of coding genes, and is critical for regulating the phosphorylation of Ser7 within the CTD. In addition, Ess1 represses the initiation of cryptic unstable transcripts (CUTs) and is required for efficient termination of mRNA transcription. Analysis using strains lacking nonsense-mediated decay suggests that as many as half of all yeast genes depend on Ess1 for efficient termination. Finally, we show that Ess1 is required for trimethylation of histone H3 lysine 4 (H3K4). Thus, Ess1 has direct effects on RNA polymerase transcription by controlling cofactor binding via conformationally induced changes in the CTD and indirect effects by influencing chromatin modification. PMID- 22778133 TI - A WNT/p21 circuit directed by the C-clamp, a sequence-specific DNA binding domain in TCFs. AB - The lymphoid enhancer factor 1/T cell factor (LEF/TCF) family of transcription factors are downstream effectors of the WNT signaling pathway, which drives colon tumorigenesis. LEF/TCFs have a DNA sequence-specific high-mobility group (HMG) box that binds Wnt response elements (WREs). The "E tail" isoforms of TCFs are alternatively spliced to include a second DNA binding domain called the C-clamp. We show that induction of a dominant negative C-clamp version of TCF1 (dnTCF1E) induces p21 expression and a stall in the growth of DLD1 colon cancer cells. Induction of a C-clamp mutant did not efficiently induce p21, nor did it stall cell growth. Microarray analysis revealed that induction of p21 by wild-type dnTCF1E (dnTCF1E(WT)) correlated with a decrease in expression of multiple p21 suppressors that act at multiple levels from transcription (SP5, YAP1, and RUNX1), RNA stability (MSI2), and protein stability (CUL4A). We show that the C clamp is a sequence-specific DNA binding domain that can make contacts with 5' RCCG-3' elements upstream or downstream of WREs. The C-clamp-RCCG interaction was critical for TCF1E-mediated transcriptional control of p21-connected target gene promoters. Our results indicate that a rapid-response WNT/p21 circuit is driven by C-clamp target gene selection. PMID- 22778134 TI - Neuronal Cbl controls biosynthesis of insulin-like peptides in Drosophila melanogaster. AB - The Cbl family proteins function as both E3 ubiquitin ligases and adaptor proteins to regulate various cellular signaling events, including the insulin/insulin-like growth factor 1 (IGF1) and epidermal growth factor (EGF) pathways. These pathways play essential roles in growth, development, metabolism, and survival. Here we show that in Drosophila melanogaster, Drosophila Cbl (dCbl) regulates longevity and carbohydrate metabolism through downregulating the production of Drosophila insulin-like peptides (dILPs) in the brain. We found that dCbl was highly expressed in the brain and knockdown of the expression of dCbl specifically in neurons by RNA interference increased sensitivity to oxidative stress or starvation, decreased carbohydrate levels, and shortened life span. Insulin-producing neuron-specific knockdown of dCbl resulted in similar phenotypes. dCbl deficiency in either the brain or insulin-producing cells upregulated the expression of dilp genes, resulting in elevated activation of the dILP pathway, including phosphorylation of Drosophila Akt and Drosophila extracellular signal-regulated kinase (dERK). Genetic interaction analyses revealed that blocking Drosophila epidermal growth factor receptor (dEGFR)-dERK signaling in pan-neurons or insulin-producing cells by overexpressing a dominant negative form of dEGFR abolished the effect of dCbl deficiency on the upregulation of dilp genes. Furthermore, knockdown of c-Cbl in INS-1 cells, a rat beta-cell line, also increased insulin biosynthesis and glucose-stimulated secretion in an ERK-dependent manner. Collectively, these results suggest that neuronal dCbl regulates life span, stress responses, and metabolism by suppressing dILP production and the EGFR-ERK pathway mediates the dCbl action. Cbl suppression of insulin biosynthesis is evolutionarily conserved, raising the possibility that Cbl may similarly exert its physiological actions through regulating insulin production in beta cells. PMID- 22778135 TI - RAD51 mutants cause replication defects and chromosomal instability. AB - RAD51 is important for restarting stalled replication forks and for repairing DNA double-strand breaks (DSBs) through a pathway called homology-directed repair (HDR). However, analysis of the consequences of specific RAD51 mutants has been difficult since they are toxic. Here we report on the dominant effects of two human RAD51 mutants defective for ATP binding (K133A) or ATP hydrolysis (K133R) expressed in mouse embryonic stem (ES) cells that also expressed normal mouse RAD51 from the other chromosome. These cells were defective for restarting stalled replication forks and repairing breaks. They were also hypersensitive to camptothecin, a genotoxin that generates breaks specifically at the replication fork. In addition, these cells exhibited a wide range of structural chromosomal changes that included multiple breakpoints within the same chromosome. Thus, ATP binding and hydrolysis are essential for chromosomal maintenance. Fusion of RAD51 to a fluorescent tag (enhanced green fluorescent protein [eGFP]) allowed visualization of these proteins at sites of replication and repair. We found very low levels of mutant protein present at these sites compared to normal protein, suggesting that low levels of mutant protein were sufficient for disruption of RAD51 activity and generation of chromosomal rearrangements. PMID- 22778137 TI - Peyer's patch M cells derived from Lgr5(+) stem cells require SpiB and are induced by RankL in cultured "miniguts". AB - Peyer's patches consist of domains of specialized intestinal epithelium overlying gut-associated lymphoid tissue (GALT). Luminal antigens reach the GALT by translocation through epithelial gatekeeper cells, the so-called M cells. We recently demonstrated that all epithelial cells required for the digestive functions of the intestine are generated from Lgr5-expressing stem cells. Here, we show that M cells also derive from these crypt-based Lgr5 stem cells. The Ets family transcription factor SpiB, known to control effector functions of bone marrow-derived immune cells, is specifically expressed in M cells. In SpiB(-/-) mice, M cells are entirely absent, which occurs in a cell-autonomous fashion. It has been shown that Tnfsf11 (RankL) can induce M cell development in vivo. We show that in intestinal organoid ("minigut") cultures, stimulation with RankL induces SpiB expression within 24 h and expression of other M cell markers subsequently. We conclude that RankL-induced expression of SpiB is essential for Lgr5 stem cell-derived epithelial precursors to develop into M cells. PMID- 22778136 TI - GATA-1 utilizes Ikaros and polycomb repressive complex 2 to suppress Hes1 and to promote erythropoiesis. AB - The transcription factor Hairy Enhancer of Split 1 (HES1), a downstream effector of the Notch signaling pathway, is an important regulator of hematopoiesis. Here, we demonstrate that in primary erythroid cells, Hes1 gene expression is transiently repressed around proerythroblast stage of differentiation. Using mouse erythroleukemia cells, we found that the RNA interference (RNAi)-mediated depletion of HES1 enhances erythroid cell differentiation, suggesting that this protein opposes terminal erythroid differentiation. This is also supported by the decreased primary erythroid cell differentiation upon HES1 upregulation in Ikaros deficient mice. A comprehensive analysis led us to determine that Ikaros favors Hes1 repression in erythroid cells by facilitating recruitment of the master regulator of erythropoiesis GATA-1 alongside FOG-1, which mediates Hes1 repression. GATA-1 is then necessary for the chromatin binding of the NuRD remodeling complex ATPase MI-2, the transcription factor GFI1B, and the histone H3K27 methyltransferase EZH2 along with Polycomb repressive complex 2. We show that EZH2 is required for the transient repression of Hes1 in erythroid cells. In aggregate, our results describe a mechanism whereby GATA-1 utilizes Ikaros and Polycomb repressive complex 2 to promote Hes1 repression as an important step in erythroid cell differentiation. PMID- 22778139 TI - Severe type IV hypersensitivity to 'black henna' tattoo. AB - A 16-year-old Bangladeshi girl presented with a 9-day history of an extensive pruritic, erythematous, papulovesicular skin eruption to both forearms. Appearance was 5 days following application of a home-made henna preparation. Examination revealed ulceration and scabbing along the whole henna pattern and early keloid formation. A diagnosis of type IV delayed hypersensitivity reaction superimposed by infection was initially made. As in this case, home-made henna preparations commonly combine commercial henna with black hair dye, paraphenylenediamine (PPD). PPD, widely known as 'black henna', darkens the pigment and precipitates the drying process. PPD is a potent contact allergen associated with a high incidence of hypersensitivity reactions. Despite treatment the patient was left with extensive keloid scarring in the pattern of the henna tattoo. PMID- 22778138 TI - High-temperature requirement protein A4 (HtrA4) suppresses the fusogenic activity of syncytin-1 and promotes trophoblast invasion. AB - Cell-cell fusion and cell invasion are essential for placental development. Human cytotrophoblasts in the chorionic villi may undergo cell-cell fusion to form syncytiotrophoblasts to facilitate nutrient-gas exchange or differentiate into extravillous trophoblasts (EVTs) to facilitate maternal-fetal circulation. The placental transcription factor glial cells missing 1 (GCM1) regulates syncytin-1 and -2 expression to mediate trophoblast fusion. Interestingly, GCM1 and syncytin 1 are also expressed in EVTs with unknown physiological functions. In this study, we performed chromatin immunoprecipitation-on-chip (ChIP-chip) analysis and identified the gene for high-temperature requirement protein A4 (HtrA4) as a GCM1 target gene, which encodes a serine protease facilitating cleavage of fibronectin and invasion of placental cells. Importantly, HtrA4 is immunolocalized in EVTs at the maternal-fetal interface, and its expression is decreased by hypoxia and in preeclampsia, a pregnancy complication associated with placental hypoxia and shallow trophoblast invasion. We further demonstrate that HtrA4 interacts with syncytin-1 and suppresses cell-cell fusion. Therefore, HtrA4 may be crucial for EVT differentiation by playing a dual role in prevention of cell-cell fusion of EVTs and promotion of their invasion into the uterus. Our study reveals a novel function of GCM1 and HtrA4 in regulation of trophoblast invasion and that abnormal HrtA4 expression may contribute to shallow trophoblast invasion in preeclampsia. PMID- 22778140 TI - Clinical presentation and operative repair of Morgagni hernia. AB - OBJECTIVES: Morgagni hernia (MH) is an uncommon type of diaphragmatic hernia. This study aimed to summarize clinically relevant data with respect to MHs in adults. METHODS: We performed a retrospective chart review of patients who underwent surgical repair of foramen due to MH at our hospitals between 1996 and 2010. Data were collected on patient demographics, presenting symptoms, modes of diagnosis, surgical procedures, surgery outcomes, recurrence of hernia and follow up of the patients. RESULTS: We included 36 patients with the mean age of 50.2 years. Of these 66.7% (n = 24) were female. Thirty-one patients had MH on the right side and 1 patient had bilateral MH. Most of the patients experienced abdominal symptoms. 72.2% of patients underwent laparotomy (n = 26, 72.2%), (n = 6, 16.7%) thoracotomy (n = 6, 16.7%), and a thoraco-abdominal approach (n = 4, 11.1%). Resection of the hernia sac and insertion of a mesh were not done in any patients. No recurrence occurred. CONCLUSIONS: We conclude that preoperative diagnosis and early diagnosis of MH by using laparotomy and thoracotomy is useful for safe and effective repair. Also we suggest that resection of the hernia sac and insertion of a mesh are not necessary. PMID- 22778141 TI - Improved perioperative neurological monitoring of coronary artery bypass graft patients reduces the incidence of postoperative delirium: the Haga Brain Care Strategy. AB - OBJECTIVES: Postoperative delirium is a major cause of morbidity and mortality after cardiovascular surgery. Risk factors for postoperative delirium include poor cerebral haemodynamics and perioperative cerebral desaturations. Our aim was to reduce the postoperative delirium rate by using a new prevention strategy called the Haga Brain Care Strategy. This study evaluates the efficacy of the implementation of the Haga Brain Care Strategy to reduce the postoperative delirium rate after elective coronary artery bypass graft (CABG) procedures. The primary endpoint was the postoperative delirium rate, and the secondary endpoint was the length of stay in the intensive care unit. METHODS: The Haga Brain Care Strategy consisted of the conventional screening protocol for delirium with the addition of preoperative transcranial Doppler examinations, perioperative cerebral oximetry, modified Rankin score, delirium risk score and (if indicated) duplex examination of the carotid arteries. In case of poor preoperative haemodynamics, the cerebral blood flow was optionally optimized by angioplasty or the patient was operated on under mild hypothermic conditions. Perioperative cerebral desaturations >20% outside the normal range resulted in intervention to restore cerebral oxygenation. Cerebral oximetry was discontinued when patients regained consciousness. Patients undergoing elective CABG procedures in 2010 were compared with patients scheduled for coronary bypass graft procedures in 2009 who had not been exposed to additional Haga Brain Care Strategy assessment. RESULTS: A total of 233 and 409 patients were included in 2009 and 2010, respectively. The number of patients subjected in 2010 to transcranial Doppler examinations, cerebral oximetry or both (Haga Brain Care Strategy) were 262 (64.1%), 201 (49.1%) and 139 (34.0%), respectively. The overall rate of postoperative delirium decreased from 31 (13.3%) in 2009 to 30 (7.3%) in 2010 (P = 0.019). A binary logistic regression model showed that the Haga Brain Care Strategy was an independent predictor of a reduced risk of developing a postoperative delirium (odd ratio = 0.37, P = 0.021). CONCLUSIONS: With the implementation of the Haga Brain Care Strategy in 2010, a reduction of the incidence of postoperative delirium in patients undergoing elective CABG procedures was observed. In addition, the length of stay in the intensive care unit showed an overall tendency to decline. The limited number of observations and the current study design do not allow a full evaluation of the Haga Brain Care Strategy but the data support the idea that a sophisticated preoperative assessment of cerebral haemodynamics and perioperative monitoring of cerebral oximetry reduce the incidence of the postoperative delirium in CABG surgery. PMID- 22778142 TI - How to improve flow during cardiopulmonary bypass in an acardia experimental model. AB - OBJECTIVES In extreme scenarios, such as hyperacute rejection of heart transplant, an urgent heart explantation might be necessary. The aim of this experimental study was to determine the feasibility and to improve the haemodynamics of a venoarterial cardiopulmonary bypass after cardiectomy. METHODS A venoarterial cardiopulmonary bypass was established in seven calves (56.4 +/- 7 kg) by the transjugular insertion to the caval axis of a self-expanding cannula, with a carotid artery return. After baseline measurements (A), ventricular fibrillation was induced (B), great arteries were clamped (C), the heart was excised and the right and left atria remnants, containing the pulmonary veins, were sutured together leaving an atrial septal defect over the cannula in the caval axis (D). Measurements were taken with the pulmonary artery clamped and declamped. RESULTS Initial pump flow was 4.16 +/- 0.75 l/min dropping to 2.9 +/- 0.63 l/min (P(AB )< 0.001) 10 min after induction of ventricular fibrillation. After cardiectomy with the pulmonary artery clamped, the pump flow increased non significantly to 3.20 +/- 0.78 l/min. After declamping, the flow significantly increased close to baseline levels (3.61 +/- 0.73 l/min, P(DB )= 0.009, P(DC )= 0.017), supporting the notion that full cardiopulmonary bypass in acardia is feasible only if adequate drainage of pulmonary circulation is assured to avoid pulmonary congestion and loss of volume from the left-to-right shunt of bronchial vessels. PMID- 22778143 TI - Delayed visceral malperfusion after Bentall procedure for type A acute aortic dissection. AB - Rapid restoration of flow into the true lumen and obliteration of a false lumen is considered the optimal approach to treating malperfusion syndrome due to acute aortic dissection. However, organ malperfusion can occasionally persist after proximal aortic graft replacement despite redirecting blood flow into the true lumen. A 35-year old man underwent the modified Bentall procedure for Stanford type A acute aortic dissection without organ malperfusion. Ischaemia of the visceral and lower extremities developed on postoperative day 8. Enhanced computed tomography (CT) revealed a thrombus in the false lumen interfering with the true lumen above the celiac trunk. We immediately performed a left axillary to-bilateral femoral artery bypass. The patient recovered uneventfully and was discharged on postoperative day 28. Although organ malperfusion persisting after proximal aortic graft replacement despite redirecting blood flow into the true lumen is rare, close observation remains imperative after central repair of type A dissection. PMID- 22778144 TI - Decision-making support system based on LCA for aseptic packaging recycling. AB - In Europe post-consumer beverage carton packages are treated in three ways: dumped in a landfill, incinerated for energy recovery, and recycled. In recent years new technologies for beverage carton recycling have been developed and tested. At the same time in Europe the collection of second-hand raw materials is becoming more efficient. In order to facilitate and justify the decision-making process, different possibilities of poly-aluminium handling were analysed. For this reason, the objective of this study was to compare carbon footprints in the whole life cycle of selected technologies and to provide decision-making with data for beverage carton recycling. The paper is based on some of the results of the project 'Sustainable Production through Innovations in small- and medium sized enterprises (SPIN)'. The SPIN project is providing small- and medium-sized enterprises with a whole set of instruments that put entrepreneurs in a position to innovate their production processes and products leading to improved business and public benefits. PMID- 22778146 TI - Complaints as indicators of health care shortcomings: which groups of patients are affected? AB - OBJECTIVE: Patient complaints about the health care system and medical services are regarded as indicators of shortcomings in health care systems. This article examines the topics of complaint raised most frequently and analyzes which groups of persons were most affected. DESIGN: Quantitative content analysis using a category system. Logistic regression was used for statistical analysis. SETTING AND PARTICIPANTS: 13 505 letters of complaint directed to the Federal Commissioner for Patient Issues in Germany between 2004 and 2007. MAIN OUTCOME MEASURES: Letters of complaint covering at least one topic were categorized to a total of 20 topics. RESULTS: The issues most frequently raised were unjust policies (23.8%), refusal or restriction of drugs (23.8%) and refusal or restriction of non-drug treatments (23.9%). The relative proportion of complaints about the physician-patient relationship increased over the period of analysis (over all 4 years: 9.3%). Multivariate analysis showed that complaints about the topics under examination were more likely to be lodged by people with statutory health insurance, people in a precarious financial situation, people with chronic disease or multimorbidity and women. CONCLUSIONS: These results provide important insights into shortcomings in the German health care system that should be seen in the context of recent reform measures. Policy makers should be made aware that certain groups of the population are particularly affected by these changes and take steps to ensure that inequalities in the health care system are not exacerbated. PMID- 22778147 TI - Anatomy and lignin distribution in reaction phloem fibres of several Japanese hardwoods. AB - BACKGROUND AND AIMS: Although tension wood formation and the structure of gelatinous fibres (G-fibres) have been widely investigated, studies of the influence of the reaction phenomenon on phloem fibres have been few and incomplete in comparison with those of xylem wood fibres. This study was undertaken to clarify the influence of stem inclination on phloem fibres using several Japanese hardwood species that produce different G-fibre types in tension wood. METHODS: Eight hardwood species were inclined at 30-45 degrees at the beginning of April. Specimens were collected in July and December. The cell-wall structure and lignin distribution of phloem fibres on both the tension and opposite sides were compared by light microscopy, ultraviolet microscopy, confocal laser scanning microscopy after staining with acriflavine, and transmission electron microscopy after staining with potassium permanganate. KEY RESULTS: Three types of changes were found in tension-side phloem fibres: (1) increases in the proportion of the syringyl unit in lignin in the S(1) and S(2) layers and compound middle lamella (Cercidiphyllum japonicum), (2) formation of unlignified gelatinous layers (Melia azedarach and Acer rufinerve) and (3) increases in the number of layers (n) in the multi-layered structure of S(1) + S(2) + n (G + L) (Mallotus japonicus). Other species showed no obvious change in cell-wall structure or lignin distribution. CONCLUSIONS: Phloem fibres of the tree species examined in our study showed three types of changes in lignin distribution and cell-wall structure. The reaction phenomenon may vary with tree species and may not be closely related to G-fibre type in tension wood. PMID- 22778145 TI - Modulation of protein phosphorylation, N-glycosylation and Lys-acetylation in grape (Vitis vinifera) mesocarp and exocarp owing to Lobesia botrana infection. AB - Grapevine (Vitis vinifera) is an economically important fruit crop that is subject to many types of insect and pathogen attack. To better elucidate the plant response to Lobesia botrana pathogen infection, we initiated a global comparative proteomic study monitoring steady-state protein expression as well as changes in N-glycosylation, phosphorylation, and Lys-acetylation in control and infected mesocarp and exocarp from V. vinifera cv Italia. A multi-parallel, large scale proteomic approach employing iTRAQ labeling prior to three peptide enrichment techniques followed by tandem mass spectrometry led to the identification of a total of 3059 proteins, 1135 phosphorylation sites, 323 N linked glycosylation sites and 138 Lys-acetylation sites. Of these, we could identify changes in abundance of 899 proteins. The occupancy of 110 phosphorylation sites, 10 N-glycosylation sites and 20 Lys-acetylation sites differentially changed during L. botrana infection. Sequence consensus analysis for phosphorylation sites showed eight significant motifs, two of which containing up-regulated phosphopeptides (X-G-S-X and S-X-X-D) and two containing down-regulated phosphopeptides (R-X-X-S and S-D-X-E) in response to pathogen infection. Topographical distribution of phosphorylation sites within primary sequences reveal preferential phosphorylation at both the N- and C termini, and a clear preference for C-terminal phosphorylation in response to pathogen infection suggesting induction of region-specific kinase(s). Lys-acetylation analysis confirmed the consensus X-K-Y-X motif previously detected in mammals and revealed the importance of this modification in plant defense. The importance of N-linked protein glycosylation in plant response to biotic stimulus was evident by an up regulated glycopeptide belonging to the disease resistance response protein 206. This study represents a substantial step toward the understanding of protein and PTMs-mediated plant-pathogen interaction shedding light on the mechanisms underlying the grape infection. PMID- 22778148 TI - Uptake of ant-derived nitrogen in the myrmecophytic orchid Caularthron bilamellatum. AB - BACKGROUND AND AIMS: Mutualistic ant-plant associations are common in a variety of plant families. Some myrmecophytic plants, such as the epiphytic orchid Caularthron bilamellatum, actively form hollow structures that provide nesting space for ants (myrmecodomatia), despite a substantial loss of water-storage tissue. This study aimed at assessing the ability of the orchid to take up nitrogen from ant-inhabited domatia as possible trade-off for the sacrifice of potential water storage capacity. METHODS: Nitrogen uptake capabilities and uptake kinetics of (15)N-labelled compounds (NH(4)(+), urea and l -glutamine) were studied in field-grown Caularthron bilamellatum plants in a tropical moist forest in Panama. Plants were either labelled directly, by injecting substrates into the hollow pseudobulbs or indirectly, by labelling of the associated ants in situ. KEY RESULTS: Caularthron bilamellatum plants were able to take up all tested inorganic and organic nitrogen forms through the inner surface of the pseudobulbs. Uptake of NH(4)(+) and glutamine followed Michaelis-Menten kinetics, but urea uptake was not saturable up to 2 mm. (15)N-labelled compounds were rapidly translocated and incorporated into vegetative and reproductive structures. By labelling ants with (15)N in situ, we were able to prove that ants transfer N to the plants under field conditions. CONCLUSIONS: Based on (15)N labelling experiments we were able to demonstrate, for the first time, that a myrmecophytic orchid is capable of actively acquiring different forms of nitrogen from its domatia and that nutrient flux from ants to plants does indeed occur under natural conditions. This suggests that beyond anti-herbivore protection host plants benefit from ants by taking up nitrogen derived from ant debris. PMID- 22778150 TI - Spatiotemporal Alignment of Visual Signals on a Special Manifold. AB - We investigate the problem of spatiotemporal alignment of videos, signals, or feature sequences extracted from them. Specifically, we consider the scenario where the spatiotemporal misalignments can be characterized by parametric transformations. Using a nonlinear analytical structure referred to as an alignment manifold, we formulate the alignment problem as an optimization problem on this nonlinear space. We focus our attention on semantically meaningful videos or signals, e.g., those describing or capturing human motion or activities, and propose a new formalism for temporal alignment accounting for executing rate variations among instances of the same video event. The strategy taken in this effort bridges the family of geometric optimization and the family of stochastic algorithms: We regard the search for optimal alignment parameters as a recursive state estimation problem for a particular dynamic system evolving on the alignment manifold. Subsequently, a Sequential Importance Sampling procedure on the alignment manifold is designed for effective alignment. We further extend the basic Sequential Importance Sampling algorithm into a new version called Stochastic Gradient Sequential Importance Sampling, in which we incorporate a steepest descent structure on the alignment manifold and provide a more efficient particle propagation mechanism. We demonstrate the performance of alignment using manifolds on several types of input data that arise in vision problems. PMID- 22778151 TI - Octree rasterization: accelerating high-quality out-of-core GPU volume rendering. AB - We present a novel approach for GPU-based high-quality volume rendering of large out-of-core volume data. By focusing on the locations and costs of ray traversal, we are able to significantly reduce the rendering time over traditional algorithms. We store a volume in an octree (of bricks); in addition, every brick is further split into regular macrocells. Our solutions move the branch-intensive accelerating structure traversal out of the GPU raycasting loop and introduce an efficient empty-space culling method by rasterizing the proxy geometry of a view dependent cut of the octree nodes. This rasterization pass can capture all of the bricks that the ray penetrates in a per-pixel list. Since the per-pixel list is captured in a front-to-back order, our raycasting pass needs only to cast rays inside the tighter ray segments. As a result, we achieve two levels of empty space skipping: the brick level and the macrocell level. During evaluation and testing, this technique achieved 2 to 4 times faster rendering speed than a current state-of-the-art algorithm across a variety of data sets. PMID- 22778149 TI - Expression of PaNAC01, a Picea abies CUP-SHAPED COTYLEDON orthologue, is regulated by polar auxin transport and associated with differentiation of the shoot apical meristem and formation of separated cotyledons. AB - BACKGROUND AND AIMS: During embryo development in most gymnosperms, the establishment of the shoot apical meristem (SAM) occurs concomitantly with the formation of a crown of cotyledons surrounding the SAM. It has previously been shown that the differentiation of cotyledons in somatic embryos of Picea abies is dependent on polar auxin transport (PAT). In the angiosperm model plant, Arabidopsis thaliana, the establishment of cotyledonary boundaries and the embryonal SAM is dependent on PAT and the expression of the CUP-SHAPED COTYLEDON (CUC) genes, which belong to the large NAC gene family. The aim of this study was to characterize CUC-like genes in a gymnosperm, and to elucidate their expression during SAM and cotyledon differentiation, and in response to PAT. METHODS: Sixteen Picea glauca NAC sequences were identified in GenBank and deployed to different clades within the NAC gene family using maximum parsimony analysis and Bayesian inference. Motifs conserved between angiosperms and gymnosperms were analysed using the motif discovery tool MEME. Expression profiles during embryo development were produced using quantitative real-time PCR. Protein conservation was analysed by introducing a P. abies CUC orthologue into the A. thaliana cuc1cuc2 double mutant. KEY RESULTS: Two full-length CUC-like cDNAs denoted PaNAC01 and PaNAC02 were cloned from P. abies. PaNAC01, but not PaNAC02, harbours previously characterized functional motifs in CUC1 and CUC2. The expression profile of PaNAC01 showed that the gene is PAT regulated and associated with SAM differentiation and cotyledon formation. Furthermore, PaNAC01 could functionally substitute for CUC2 in the A. thaliana cuc1cuc2 double mutant. CONCLUSIONS: The results show that CUC-like genes with distinct signature motifs existed before the separation of angiosperms and gymnosperms approx. 300 million years ago, and suggest a conserved function between PaNAC01 and CUC1/CUC2. PMID- 22778152 TI - The propagation approach for computing biochemical reaction networks. AB - We introduce propagation models (PMs), a formalism able to express several kinds of equations that describe the behavior of biochemical reaction networks. Furthermore, we introduce the propagation abstract data type (PADT), which separates concerns regarding different numerical algorithms for the transient analysis of biochemical reaction networks from concerns regarding their implementation, thus allowing for portable and efficient solutions. The state of a propagation abstract data type is given by a vector that assigns mass values to a set of nodes, and its next operator propagates mass values through this set of nodes. We propose an approximate implementation of the next operator, based on threshold abstraction, which propagates only "significant" mass values and thus achieves a compromise between efficiency and accuracy. Finally, we give three use cases for propagation models: the chemical master equation (CME), the reaction rate equation (RRE), and a hybrid method that combines these two equations. These three applications use propagation models in order to propagate probabilities and/or expected values and variances of the model's variables. PMID- 22778153 TI - The novel BCR-ABL and FLT3 inhibitor ponatinib is a potent inhibitor of the MDR associated ATP-binding cassette transporter ABCG2. AB - Ponatinib is a novel tyrosine kinase inhibitor with potent activity against BCR ABL with mutations, including T315I, and also against fms-like tyrosine kinase 3. We tested interactions between ponatinib at pharmacologically relevant concentrations of 50 to 200 nmol/L and the MDR-associated ATP-binding cassette (ABC) proteins ABCB1, ABCC1, and ABCG2. Ponatinib enhanced uptake of substrates of ABCG2 and ABCB1, but not ABCC1, in cells overexpressing these proteins, with a greater effect on ABCG2 than on ABCB1. Ponatinib potently inhibited [(125)I]-IAAP binding to ABCG2 and ABCB1, indicating binding to their drug substrate sites, with IC(50) values of 0.04 and 0.63 MUmol/L, respectively. Ponatinib stimulated ABCG2 ATPase activity in a concentration-dependent manner and stimulated ABCB1 ATPase activity at low concentrations, consistent with it being a substrate of both proteins at pharmacologically relevant concentrations. The ponatinib IC(50) values of BCR-ABL-expressing K562 cells transfected with ABCB1 and ABCG2 were approximately the same as and 2-fold higher than that of K562, respectively, consistent with ponatinib being a substrate of both proteins, but inhibiting its own transport, and resistance was also attenuated to a small degree by ponatinib induced downregulation of ABCB1 and ABCG2 cell-surface expression on resistant K562 cells. Ponatinib at pharmacologically relevant concentrations produced synergistic cytotoxicity with ABCB1 and ABCG2 substrate chemotherapy drugs and enhanced apoptosis induced by these drugs, including daunorubicin, mitoxantrone, topotecan, and flavopiridol, in cells overexpressing these transport proteins. Combinations of ponatinib and chemotherapy drugs warrant further testing. PMID- 22778154 TI - Enhancement of synthetic lethality via combinations of ABT-888, a PARP inhibitor, and carboplatin in vitro and in vivo using BRCA1 and BRCA2 isogenic models. AB - Individuals with an inherited BRCA1 or BRCA2 mutation have an elevated risk of developing breast cancer. The resulting tumors typically lack homologous recombination repair as do a subset of sporadic tumors with acquired BRCA deficiency. Clinical responses to monotherapy with platinum drugs or poly PARP inhibitors (PARPi) have been shown for BRCA-associated cancers. However, there are limited data on combination therapy with PARPi and platinum drugs, the mechanism of action of this combination, and the role of BRCA1 or BRCA2 in chemosensitivity. We compared the efficacy of ABT-888 (a PARPi) with that of cisplatin or carboplatin (platinum drugs) alone or in combinations by examining the survival of treated Brca-proficient and -deficient mouse embryonic stem cells. In addition, drug-induced growth inhibition of a BRCA1 and a BRCA2 null cell line were compared with their isogenic BRCA-complemented lines. Although each monotherapy killed or inhibited proliferation of Brca/BRCA-deficient cells, an enhanced effect was observed after treatment with ABT-888 in combination with carboplatin. Moreover, the ABT-888/carboplatin combination delayed tumor growth in Brca2 xenografts. The drugs caused DNA damage and apoptosis. Along with greater PARP activity in Brca/BRCA-deficient cells, these effects correlated with increased chemosensitivity. Our data suggest that ABT-888 and carboplatin combination treatment will be more successful than monotherapy in addressing many BRCA-associated cancers. A randomized phase II trial has recently been initiated to test this hypothesis to assist in the discovery of more effective therapies for patients with BRCA. PMID- 22778155 TI - Fibroblast growth factor receptor 2 IIIc as a therapeutic target for colorectal cancer cells. AB - A high percentage of colorectal carcinomas overexpress a lot of growth factors and their receptors, including fibroblast growth factor (FGF) and FGF receptor (FGFR). We previously reported that FGFR2 overexpression was associated with distant metastasis and that FGFR2 inhibition suppressed cell growth, migration, and invasion. The FGFR2 splicing isoform FGFR2IIIb is associated with well differentiated histologic type, tumor angiogenesis, and adhesion to extracellular matrices. Another isoform, FGFR2IIIc, correlates with the aggressiveness of various types of cancer. In the present study, we examined the expression and roles of FGFR2IIIc in colorectal carcinoma to determine the effectiveness of FGFR2IIIc-targeting therapy. In normal colorectal tissues, FGFR2IIIc expression was weakly detected in superficial colorectal epithelial cells and was not detected in proliferative zone cells. FGFR2IIIc-positive cells were detected by immunohistochemistry in the following lesions, listed in the order of increasing percentage: hyperplastic polyps < low-grade adenomas < high-grade adenomas < carcinomas. FGFR2IIIc immunoreactivity was expressed in 27% of colorectal carcinoma cases, and this expression correlated with distant metastasis and poor prognosis. FGFR2IIIc-transfected colorectal carcinoma cells showed increased cell growth, soft agar colony formation, migration, and invasion, as well as decreased adhesion to extracellular matrices. Furthermore, FGFR2IIIc-transfected colorectal carcinoma cells formed larger tumors in subcutaneous tissues and the cecum of nude mice. Fully human anti-FGFR2IIIc monoclonal antibody inhibited the growth and migration of colorectal carcinoma cells through alterations in cell migration, cell death, and development-related genes. In conclusion, FGFR2IIIc plays an important role in colorectal carcinogenesis and tumor progression. Monoclonal antibody against FGFR2IIIc has promising potential in colorectal carcinoma therapy. PMID- 22778156 TI - Quantifying structures in the ocular fundus. PMID- 22778157 TI - A single point mutation in GmHMA3 affects Cadmium (Cd) translocation and accumulation in soybean seeds. PMID- 22778158 TI - Co-production of SFO-1 and DHA-1 beta-lactamases and 16S rRNA methylase ArmA in clinical isolates of Klebsiella pneumoniae. AB - OBJECTIVES: To investigate the epidemiology and genetic characteristics of the plasmid-mediated extended-spectrum beta-lactamase (ESBL) gene bla(SFO-1) in clinical isolates of ESBL-producing Klebsiella pneumoniae and Escherichia coli. METHODS: The prevalence of the bla(SFO-1) gene was examined by PCR amplification. Conjugation and transformation experiments were performed and the presence of antimicrobial resistance determinants was investigated by the PCR method. The genetic environments of the bla(SFO-1) and armA genes were determined by direct sequencing of plasmid pHS20. Plasmids were typed by PCR-based replicon typing. PFGE and multilocus sequence typing were performed on SFO-producing strains. RESULTS: Of 158 ESBL-producing strains of K. pneumoniae, 3 (1.9%) carried the bla(SFO-1) gene. All of the SFO-producing isolates belonged to the ST11 epidemic clone, with a single PFGE type and had high-level resistance to third-generation cephalosporins, aminoglycosides and ciprofloxacin. The bla(SFO-1) gene was co transferred with the armA, aac(6')-Ib-cr and bla(TEM-1) genes by transformation, whereas the armA, bla(DHA-1) and qnrB4 genes were co-transferred by conjugation. The armA genes were located within the composite transposon Tn1548 on two different plasmids in the strain 08-129. The bla(SFO-1) gene was located upstream of an ampR gene from the coding region and flanked by two inverted repeats of IS26. Plasmids carrying bla(DHA-1) were identified as IncFII, while the bla(SFO 1)-bearing plasmids were non-typeable. CONCLUSIONS: Although SFO-1 is a low occurrence ESBL, it has been captured by a plasmid accumulating multiple resistance determinants including armA and aac(6')-Ib-cr, and accompanied by a large DHA-1-bearing IncFII plasmid in a prevalent K. pneumoniae ST11 clone. PMID- 22778159 TI - Adherence to recommendations for the use of antifungal agents in a tertiary care hospital. AB - OBJECTIVES: The aim of our study was to assess the adherence to labelling and international guidelines for antifungal prescribing. METHODS: A retrospective study was performed in intensive care units in addition to the oncology and haematology department, which covered 70% of antifungal consumption at Hautepierre Hospital, Strasbourg, France. On reviewing medical charts, the antifungal prescription was examined in relation to the recommendations of indication, dosage, risk of drug-drug interactions and, where appropriate, antifungal susceptibility testing. Treatments were considered appropriate, inappropriate or debatable. RESULTS: Between January and April 2007, 199 treatments were given for 179 different episodes in 133 adult patients. Treatments were prescribed for pre-emptive or targeted therapy (n = 90, with 60 for candidiasis, 26 for aspergillosis and 4 for other mould diseases), empirical therapy (n = 17) and primary (n = 81) or secondary (n = 11) prophylaxis. Fluconazole accounted for 67% of prescriptions, followed by voriconazole (19%), caspofungin (10%), posaconazole (2%), conventional or liposomal amphotericin B (2%), itraconazole (<1%) and terbinafine (<1%). Indication and dosage were found to be appropriate in 65% and 62% of cases, inappropriate in 22% and 21%, and debatable in 13% and 17%, respectively. The overall (by combining all assessment criteria) rate of inappropriate use was 40%. The overall survival rate at 12 weeks was highest in patients receiving appropriate therapy (81% versus 72% and 68% in the debatable and inappropriate therapy groups, respectively), with between-group differences not being significant (P = 0.49). CONCLUSIONS: Our evaluation revealed a high proportion of inappropriate or debatable use of antifungal agents, while highlighting significant issues, such as inadequate dosage or indications. PMID- 22778161 TI - Statins: the good, the bad and the ugly. PMID- 22778162 TI - Leadership on prescription drugs needed. PMID- 22778163 TI - Floater panic could cause overreferral. PMID- 22778165 TI - Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the American Heart Association and the American Diabetes Association. PMID- 22778166 TI - Phytophthora borealis and Phytophthora riparia, new species in Phytophthora ITS Clade 6. AB - Phytophthora borealis and Phytophthora riparia, identified in recent Phytophthora surveys of forest streams in Oregon, California and Alaska, are described as new species in Phytophthora ITS Clade 6. They are similar in growth form and morphology to P. gonapodyides and are predominantly sterile. They present unique DNA sequences, however, and differ in temperature/growth relations and geographic distribution. PMID- 22778167 TI - Gene expression profiling of the plant pathogenic basidiomycetous fungus Rhizoctonia solani AG 4 reveals putative virulence factors. AB - Rhizoctonia solani is a ubiquitous basidiomycetous soilborne fungal pathogen causing damping-off of seedlings, aerial blights and postharvest diseases. To gain insight into the molecular mechanisms of pathogenesis a global approach based on analysis of expressed sequence tags (ESTs) was undertaken. To get broad gene-expression coverage, two normalized EST libraries were developed from mycelia grown under high nitrogen-induced virulent and low nitrogen/methylglucose induced hypovirulent conditions. A pilot-scale assessment of gene diversity was made from the sequence analyses of the two libraries. A total of 2280 cDNA clones was sequenced that corresponded to 220 unique sequence sets or clusters (contigs) and 805 singlets, making up a total of 1025 unique genes identified from the two virulence-differentiated cDNA libraries. From the total sequences, 295 genes (38.7%) exhibited strong similarities with genes in public databases and were categorized into 11 functional groups. Approximately 61.3% of the R. solani ESTs have no apparent homologs in publicly available fungal genome databases and are considered unique genes. We have identified several cDNAs with potential roles in fungal pathogenicity, virulence, signal transduction, vegetative incompatibility and mating, drug resistance, lignin degradation, bioremediation and morphological differentiation. A codon-usage table has been formulated based on 14694 R. solani EST codons. Further analysis of ESTs might provide insights into virulence mechanisms of R. solani AG 4 as well as roles of these genes in development, saprophytic colonization and ecological adaptation of this important fungal plant pathogen. PMID- 22778169 TI - Two new Tricladium species from streams in Alaska. AB - Two new species of aquatic hyphomycetes in the genus Tricladium are described from streams in Alaska, USA. Both species were isolated from submerged decaying sedges. Tricladium kelleri has blackish colonies and typical tricladioid conidia formed on sympodial conidiogenous cells. Tricladium alaskense has conidia with fine elements and 0-4 lateral branches; conidia are formed on sympodial conidiogenous cells. The two species are compared to other species in the genus and related genera using morphological characters and/or rDNA sequencing data (ITS and 28S). Molecular phylogenetic analysis placed both species in the Helotiales. PMID- 22778168 TI - Multigene phylogenetic analyses of the Thelonectria coronata and T. veuillotiana species complexes. AB - Thelonectria is a recently established genus of common and ubiquitous fungi on woody hosts, previously placed in the genus Neonectria. Thelonectria coronata and T. veuillotiana occur sympatrically in tropical, subtropical and temperate regions. Previous taxonomic studies including T. coronata and T. veuillotiana suggested these fungi could represent species complexes; however, the morphological features used to define species exhibited few differences useful for testing this hypothesis. To assess the status of T. coronata and T. veuillotiana, phylogenetic analyses of six genomic regions were combined with a morphological examination of specimens. A multi-gene phylogeny reconstructed with maximum parsimony, maximum likelihood and Bayesian approaches identified five phylogenetic groups in T. coronata and six in T. veuillotiana. As is common for cryptic species, unequivocal diagnostic morphological characters could not be identified; however, average values of morphological traits correspond to the phylogenetic groups. An increased number of non-synonymous/synonymous substitutions in the beta-tubu-lin gene and a decreased or absent production of conidia were detected within the T. coronata complex, possibly indicating the homothallic nature of these isolates. T. coronata and T. veuillotiana and related species are described and illustrated here; a dichotomous key to all species is provided. PMID- 22778170 TI - Piracy in the high trees: ectomycorrhizal fungi from an aerial 'canopy soil' microhabitat. AB - The mantle of dead organic material ("canopy soil") associated with the mats of vascular and nonvascular epiphytes found on the branches of trees in the temperate rainforests along the southwestern coast of the South Island of New Zealand were examined for evidence of ectomycorrhizal fungi. DNA sequencing and cluster analysis were used to identify the taxa of fungi present in 74 root tips collected from the canopy soil microhabitat of three old growth Nothofagus menziesii trees in the South West New Zealand World Heritage Area. A diverse assemblage of ectomycorrhizal fungi was found to infect an extensive network of adventitious canopy roots of Nothofagus menziesii in this forest, including 14 phylotypes from nine genera of putative ectomycorrhizal fungi. Seven of the genera identified previously were known to form ectomycorrhizas with terrestrial roots of Nothofagus: Cortinarius, Russula, Cenococcum, Thelephora/Tomentella, Lactarius and Laccaria; two, Clavulina and Leotia, previously have not been reported forming ectomycorrhizas with Nothofagus. Canopy ectomycorrhizas provide an unexpected means for increased host nutrition that may have functional significance in some forest ecosystems. Presumably, canopy ectomycorrhizas on host adventitious roots circumvent the tree-ground-soil nutrient cycle by accessing a wider range of nutrients directly in the canopy than would be possible for non-mycorrhizal or arbuscular mycorrhizal canopy roots. In this system, both host and epiphytes would seem to be in competition for the same pool of nutrients in canopy soil. PMID- 22778171 TI - Electron microscopy studies of basidiosporogenesis in Agaricus brasiliensis. AB - The objective of this work was to study the basidiosporogenesis and the intraspecific variation in the number of basidiospores produced per basidium in Agaricus brasiliensis with transmission (TEM) and scanning electron microscopy (SEM). A. brasiliensis produces predominantly tetrasporic basidia, but this trait may vary depending on the strain. For certain strains, such as CS2 and CS7, the frequency of bisporic and trisporic basidia was similar to, or greater than, that of tetrasporic strains. These results suggest that some strains of A. brasiliensis may be amphithallic; however, this behavior is variable and strain dependent. The development of basidia and basidiospores occurs asynchronously during basidiocarp production. The basidiospore cell wall is composed of three distinct layers and presents variable thickness. The conspicuous presence of lipid bodies also was observed in the basidiospores, while nuclei, mitochondria, vacuoles and dolipore septa could be visualized only in the basidia. The basidiospores generally are produced free but also may be enveloped by an extracellular matrix with unknown chemical composition. The presence of connection hyphae linking the basidia was observed for the first time in A. brasiliensis. This characteristic, so far not reported for other fungi, may represent a specific strategy of A. brasiliensis for exchanging nuclei and other cell material between basidial cells during basidiosporogenesis. PMID- 22778172 TI - GnRH receptors in cancer: from cell biology to novel targeted therapeutic strategies. AB - The crucial role of pituitary GnRH receptors (GnRH-R) in the control of reproductive functions is well established. These receptors are the target of GnRH agonists (through receptor desensitization) and antagonists (through receptor blockade) for the treatment of steroid-dependent pathologies, including hormone-dependent tumors. It has also become increasingly clear that GnRH-R are expressed in cancer tissues, either related (i.e. prostate, breast, endometrial, and ovarian cancers) or unrelated (i.e. melanoma, glioblastoma, lung, and pancreatic cancers) to the reproductive system. In hormone-related tumors, GnRH-R appear to be expressed even when the tumor has escaped steroid dependence (such as castration-resistant prostate cancer). These receptors are coupled to a G(alphai)-mediated intracellular signaling pathway. Activation of tumor GnRH-R by means of GnRH agonists elicits a strong antiproliferative, antimetastatic, and antiangiogenic (more recently demonstrated) activity. Interestingly, GnRH antagonists have also been shown to elicit a direct antitumor effect; thus, these compounds behave as antagonists of GnRH-R at the pituitary level and as agonists of the same receptors expressed in tumors. According to the ligand-induced selective-signaling theory, GnRH-R might assume various conformations, endowed with different activities for GnRH analogs and with different intracellular signaling pathways, according to the cell context. Based on these consistent experimental observations, tumor GnRH-R are now considered a very interesting candidate for novel molecular, GnRH analog-based, targeted strategies for the treatment of tumors expressing these receptors. These agents include GnRH agonists and antagonists, GnRH analog-based cytotoxic (i.e. doxorubicin) or nutraceutic (i.e. curcumin) hybrids, and GnRH-R-targeted nanoparticles delivering anticancer compounds. PMID- 22778173 TI - Balloon-like intimal flap in the left ventricle. PMID- 22778174 TI - Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure. AB - AIMS: Cinaciguat (BAY 58-2667) is a novel soluble guanylate cyclase activator. This study evaluated the haemodynamic effect and safety of cinaciguat added to standard therapy in patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: In this placebo-controlled, phase IIb study (NCT00559650), 139 patients admitted with ADHF, pulmonary capillary wedge pressure (PCWP) >=18 mmHg, left ventricular ejection fraction <40%, and a pre-existing need for invasive haemodynamic monitoring were randomized 2:1 to cinaciguat:placebo (continuous i.v. infusion). The dose was titrated for 8 h and maintained for 16 40 h (starting dose: 100 MUg/h). At 8 h, mean PCWP changed from 25.7 +/- 5.0 mmHg by -7.7 mmHg with cinaciguat and from 25.0 +/- 5.3 mmHg by -3.7 mmHg with placebo (P < 0.0001). The mean right atrial pressure changed from 12.4 +/- 5.3 mmHg by 2.7 mmHg with cinaciguat and from 11.8 +/- 4.9 mmHg by -0.6 mmHg with placebo (P= 0.0019). Cinaciguat also decreased the pulmonary and systemic vascular resistance and the mean arterial pressure, and increased the cardiac index (all P < 0.0001 vs. placebo). Systolic blood pressure changed by -21.6 +/- 17.0 mmHg with cinaciguat and -5.0 +/- 14.5 mmHg with placebo. Adverse events were experienced by 71 and 45% of patients receiving cinaciguat and placebo, respectively. No adverse effects on the 30-day mortality were seen; however, the trial was stopped prematurely due to an increased occurrence of hypotension at cinaciguat doses >=200 ug/h. CONCLUSION: Cinaciguat unloaded the heart in patients with ADHF. However, high doses were associated with hypotension. PMID- 22778175 TI - Meta-analysis of clinical studies comparing coronary artery bypass grafting with percutaneous coronary intervention in patients with end-stage renal disease. AB - End-stage renal disease (ESRD) patients are at high risk for coronary artery disease (CAD). The optimal revascularization strategy remains unknown. We performed a meta-analysis of retrospective observational trials to compare coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for ESRD patients with CAD. A search of published reports was conducted to identify clinical studies comparing CABG with PCI in ESRD patients with CAD with a minimal follow-up of 12 months. Sixteen studies included 32 350 ESRD patients with revascularization. Compared with PCI, CABG was associated with a lower risk for late mortality [relative risk (RR) 0.90, 95% confidence interval (CI) 0.87 0.93], myocardial infarction event (RR 0.64, 95% CI: 0.61-0.68), repeat revascularization event (RR 0.22, 95% CI: 0.16-0.31) and cumulative events (RR 0.69, 95% CI: 0.65-0.73), despite having a higher risk for early mortality (RR 1.98, 95% CI: 1.51-2.60). In conclusion, the long-term results of PCI in ESRD patients are dismal, and CABG is significantly superior to PCI in this subset of patients. PMID- 22778177 TI - Association between serum 25-hydroxyvitamin D and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-94. AB - BACKGROUND: The role of vitamin D in kidney stone disease is controversial. Current evidence is inconsistent and existing studies are limited by small sample populations. METHODS: We used the third National Health and Nutrition Examination Survey (NHANES III), a large US population-based cross-sectional study, to determine the independent association between serum 25-hydroxyvitamin D [25(OH)D] concentration and prevalent kidney stone disease in a sample of 16 286 men and women aged 18 years or older. A prevalent kidney stone was defined as self-report of any previous episode of kidney stones. RESULTS: Among 16 286 adult participants, 759 subjects reported a history of previous kidney stones. Concentrations of serum 25(OH)D were not different between stone formers and non stone formers (mean 29.28 versus 29.55 ng/mL, P = 0.57). Higher 25(OH)D concentration was not associated with increased odds ratio (OR) for previous kidney stones [OR = 0.99; 95% confidence interval (CI) 0.99-1.01] after adjustment for age, sex, race, history of hypertension, diabetes, body mass index, diuretic use and serum calcium. Furthermore, after we divided 25(OH)D concentrations into quartiles, or into groups using clinically significant cut offs (e.g. 40 and 50 ng/mL), still no significant differences were found in stone formation in group comparisons. CONCLUSIONS: High serum 25(OH)D concentrations are not associated with prevalent kidney stone disease in NHANES III participants. Prospective studies are needed to clarify the relationship between vitamin D and kidney stone formation, and whether nutritional vitamin D supplementation will increase risk of stone recurrence. PMID- 22778178 TI - Characterization of vitamin D-deficient klotho(-/-) mice: do increased levels of serum 1,25(OH)2D3 cause disturbed calcium and phosphate homeostasis in klotho(-/ ) mice? AB - BACKGROUND: Klotho(-/-) mice display disturbed Ca(2+) and vitamin D homeostasis. Renal cytochrome p450 27b1 (Cyp27b1), the enzyme that catalyzes the hydrolysis to 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), is increased in klotho(-/-) mice, and a 1,25(OH)(2)D(3)-deficient diet partially normalized Ca(2+) homeostasis in these klotho(-/-) mice. The aim of the present study was to further delineate the interplay between 1,25(OH)(2)D(3) and klotho and their relative contribution to the Ca(2+) homeostasis of klotho(-/-) mice. METHODS: Double-klotho(-/-)/Cyp27b1( /-) mice were generated and mice aged 8-12 weeks were housed in metabolic cages to collect 24-h urine. Blood samples were taken and the animals were sacrificed, and the kidney and duodenum tissues were sampled for RNA extraction. The bone was fixed in 10% v/v formalin and analysed by microcomputed tomography (MUCT) scans. RESULTS: Klotho(-/-)/Cyp27b1(-/-) mice, like Cyp27b1(-/-) mice, displayed significantly decreased serum total calcium concentrations compared with wild type mice (1.44 +/- 0.03 and 2.25 +/- 0.02 mM) along with normal urinary total calcium excretion. Hyperphosphataemia of klotho(-/-) mice normalized to wild-type levels in klotho(-/-)/Cyp27b1(-/-) mice. The mRNA levels of duodenal transient receptor potential vanilloid subtype 6 (TRPV6) and calcium-binding protein-D(9K), and renal calbindin-D(28K) and NCX1 were significantly reduced in the double knockouts compared with wild-type or klotho(-/-) mice. Elevated TRPV5 protein levels in klotho(-/-) mice normalized to wild type in klotho(-/-)/Cyp27b1(-/-) mice, but were decreased in Cyp27b1(-/-) mice. MUCT scans showed that klotho(-/ )/Cyp27b1(-/-) mice, as Cyp27b1(-/-) mice, display significant bone hypomineralization and severely decreased bone mass. Klotho(-/-) mice show a reduced bone mass and increased trabecular numbers. CONCLUSIONS: Klotho(-/ )/Cyp27b1(-/-) mice resemble Cyp27b1(-/-) mice. Since 1,25(OH)(2)D(3) is absent in these mice, our results imply that Ca(2+) homeostasis in klotho(-/-) mice is affected by their excessive 1,25(OH)(2)D(3) levels. PMID- 22778180 TI - How much of the regional variation in RRT incidence rates within the UK is explained by the health needs of the general population? AB - BACKGROUND: Variation in end-stage renal disease treatment rates in the UK persist after adjustment for socio-demographic factors. METHODS: UK-wide ecological study using population socio-demographic factors, health status characteristics and access to health services factor in to explain the incidence of renal replacement therapy (RRT). RESULTS: There was a 6% higher incidence rate of RRT per standard deviation (SD) increase in area diabetes prevalence after adjustment for area level socio-economic deprivation status and the proportion of non-white residents [incidence rate ratio adjusted (IRR adjusted) 1.06 (95% confidence interval 1.03,1.09), P < 0.001]. A 3% lower-adjusted RRT incidence rate was seen with each SD higher proportion of diabetics achieving an HbA1c of <7.5% [IRR 0.97 (0.94, 1.00), P = 0.03]. Hypertension prevalence was independently associated with an 8% higher RRT incidence rate per SD increase [IRR adjusted 1.08 (1.04, 1.11), P < 0.001] and an SD increase in life expectancy in an area was independently associated with 7% lower RRT incidence rate [IRR adjusted 0.93 (0.91, 0.96), P < 0.001]. An SD increase in premature cardiovascular (CV) mortality rate in an area was also independently associated with RRT incidence rates [IRR adjusted 1.06 (1.03, 1.09), P < 0.001]. Rates of coronary artery bypass grafting (CABG)/angioplasty and knee replacement were positively associated with RRT incidence, but mammography uptake was not associated. In total, 31% of the regional variation in RRT incidence could be explained by these factors. CONCLUSIONS: Diabetes prevalence, the proportion of diabetics achieving good glycaemic control, hypertension prevalence, life expectancy, premature CV mortality, CABG/angioplasty and knee replacement rates were all associated with RRT incidence. A third of the regional variation in RRT incidence between areas can be explained by these demographic, health and access to health services factors. PMID- 22778179 TI - Cytokine production increases and cytokine clearance decreases in mice with bilateral nephrectomy. AB - BACKGROUND: Serum cytokines are increased in patients with acute kidney injury (AKI) and predict increased mortality. It is widely assumed that increased renal production of cytokines is the source of increased serum cytokines; the role of extra-renal cytokine production and impaired renal cytokine clearance is less well studied. We hypothesized that cytokine production in AKI was mononuclear phagocyte dependent, independent of production by the kidneys, and that serum cytokine clearance would be impaired in AKI. METHODS: Bilateral nephrectomy was used as a model of AKI to assess cytokine production independent of kidney cytokine production. Mononuclear phagocytes were depleted utilizing intravenous (IV) administration of liposome-encapsulated clodronate (LEC). Twenty-three serum cytokines were determined utilizing a multiplex cytokine kit. Proteins for cytokines were determined in the spleen and liver by enzyme-linked immunosorbent assay. Recombinant cytokines were injected by IV into mice with bilateral nephrectomy to determine the effect of absent kidney function on serum cytokine clearance. RESULTS: Serum interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), IL-10, IL-1beta, monocyte chemotactic protein 1 (MCP-1), IL-5 and eotaxin were increased in the serum of mice after bilateral nephrectomy and were reduced with LEC. Serum IL-12p40 and regulated upon activation, normal T-cell expressed, and secreted (RANTES) were increased after bilateral nephrectomy and were further increased with LEC. Spleen IL-6, CXCL1, IL-10 and IL-1beta and liver IL-6 and IL-10 were increased after bilateral nephrectomy. After IV injection, IL 6, CXCL1, IL-10 and IL-1beta had a prolonged serum cytokine appearance in mice with bilateral nephrectomy versus sham operation. CONCLUSIONS: Increased mononuclear phagocyte production and impaired renal clearance contribute to serum cytokine accumulation in AKI, independent of kidney injury. The effect of AKI on cytokine production and clearance may contribute to the increased mortality of patients with AKI. PMID- 22778181 TI - Vasopressin increases S261 phosphorylation in AQP2-P262L, a mutant in recessive nephrogenic diabetes insipidus. AB - BACKGROUND: Mutations in the aquaporin-2 (AQP2) gene cause nephrogenic diabetes insipidus (NDI), a renal disorder characterized by polyuria due to a lacking antidiuretic response to vasopressin. While most AQP2 mutants in recessive NDI are misfolded and retained in the endoplasmic reticulum, AQP2-P262L in NDI was impaired in its vasopressin-dependent translocation from vesicles to the plasma membrane. METHODS: Vasopressin-induced translocation of AQP2 coincides with AQP2 phosphorylation at S256, S264 and T269 and dephosphorylation at S261. Since P262 lies adjacent to S261, we tested whether a changed phosphorylation could underlie AQP-P262L missorting in NDI. RESULTS: In polarized cells, AQP2-P262L expressed as a double 29/30 kDa band, whereas wt-AQP2 expressed only as a 29 kDa band. Phosphatase treatment revealed that the 30 kDa AQP2-P262L band was due to changed phosphorylation. The use of newly developed phospho-specific antibodies showed that forskolin not only increased pS256 and pT269, but, in contrast to wt-AQP2, also pS261 in AQP2-P262L. The expression of AQP2-P262L proteins in which S261 phosphorylation was prevented (S261A), however, was still missorted to vesicles/basolateral membrane, despite the absence of the 30 kDa band. CONCLUSIONS: Together, our data reveal that vasopressin induces instead of reduces the phosphorylation of S261 in AQP2-P262L, but it remains to be established whether the changed phosphorylation causes its missorting in NDI. PMID- 22778182 TI - Cannabinoid hyperemesis. AB - A 21-year-old woman presented with a 4-week history of sudden onset vomiting, nausea and anorexia. Questioning revealed that she had a 7-year history of heavy cannabis use (smoking). She did not describe abdominal pain, change in bowel habit, antibiotic use, foreign travel or contact with gastroenteritis. Biochemistry results demonstrated mild metabolic derangement with a low potassium and a low bicarbonate, and urine toxicology was positive for cannabinoids. Other investigations, including a full blood count, renal function tests, liver function tests, a coagulation sample, an ECG, urinary beta-hCG and a CT head scan, were all normal. A diagnosis of cannabinoid hyperemesis was made and her symptoms resolved after treatment with intravenous fluids, antiemetics and abstinence from cannabis. Since her discharge and abstinence she has had several relapses, each related to cannabis use and each resolving with abstinence. The patient is now seeking cognitive behavioural therapy to achieve permanent abstinence. PMID- 22778183 TI - Right thoracoabdominal stab injury penetrating the liver and gallbladder: lessons in penetrating knife wounds to the chest and abdomen. AB - The authors report a patient who suffered a penetrating knife injury to the right thoracoabdominal region which penetrated through the liver and both sides of the gallbladder. This injury was treated successfully by laparotomy and cholecystectomy. PMID- 22778184 TI - Cerebrospinal fluid leak associated with nasal continuous positive airway pressure treatment for obstructive sleep apnoea. AB - Clear rhinorrhoea is a common symptom in patients with obstructive sleep apnoea (OSA), which may worsen with nasal continuous positive airway pressure treatment (nCPAP). However, rhinorrhoea can also be the presenting symptom of cerebrospinal fluid (CSF) leak, which is due to a communication between the subarachnoid space and the nasal cavity or sinuses. We report another case of a patient with OSA in whom CSF leak developed following the initiation of nCPAP treatment. PMID- 22778185 TI - The striatocapsular infarction and its aftermaths. AB - Ischaemic stroke syndromes in the vascular territory of middle cerebral artery may have atypical presentation and radiographic findings because of the variable anatomy of that artery. Therefore, misdiagnosis of these syndromes as neoplastic or infectious processes is not uncommon. This case describes a 69-year-old comatose woman who was referred to us as having 'a brain tumour with massive surrounding oedema.' Further work-up revealed that she had a large left-sided lenticular nuclear infarction with some extension into the surrounding areas-the striatocapsular infarction. PMID- 22778187 TI - Internal jugular phlebectasia in an African adult. AB - Jugular vein phlebectasia is a rare venous anomaly commonly presenting as a unilateral neck swelling in children and adults. Its aetiology is unknown and its detection may have increased with availability of better imaging facilities. Due to its rarity, a high index of suspicion is required once other causes of neck swelling are excluded. The few reported cases are mainly in children and non Africans adults. The authors report the case of a 54-year-old Nigerian woman presenting for the first time with a progressive, intermittent, painless right neck swelling, which was demonstrated on Doppler ultrasound and CT angiography to be an internal jugular phlebectasia. She had satisfactory surgical excision of the dilated segment for cosmetic reasons. PMID- 22778186 TI - Appendico-colic fistula complicating appendicitis in cystic fibrosis. AB - The case of a boy with cystic fibrosis who presented with an unusual complication of appendicitis is reported. Delayed presentation, with complications of appendicitis such as perforation and abscess formation, is not uncommon in cystic fibrosis; however, this case represents the first report of an isolated appendico colic fistula following appendicitis in association with cystic fibrosis. PMID- 22778188 TI - Genital oedema associated with femoral central venous access in a premature baby. PMID- 22778189 TI - Gastric ulcers and swollen kidneys: a rare diagnosis complicating Crohn's disease. AB - We present a case of a 48-year-old woman with Crohn's colitis admitted with abdominal pain and fever. She had been started on azathioprine 6 months before presentation and had received three doses of infliximab. Abdominal CT scan revealed a liver abscess. Azathioprine was stopped and antibiotics started. She was subsequently discharged with follow-up imaging planned. She presented 3 weeks later with haematemesis. Gastroscopy revealed multiple gastric ulcers. A repeat CT scan showed bilateral renal masses and a renal biopsy was arranged. Gastric and renal biopsies were consistent with B cell lymphoma. Chemotherapy was started and resulted in improvement in CT scan findings as well as ulcer healing. PMID- 22778190 TI - Primary signet ring cell carcinoma of gall bladder: report of an extremely rare histological type of primary gall bladder carcinoma. AB - Signet ring cell carcinoma is an extremely rare type of gall bladder carcinoma composed overwhelmingly (90%) of signet ring cells. It is necessary to exclude a gastric or colonic signet ring cell carcinoma secondarily involving the gall bladder. The primary aim of this case report is to describe the histopathological aspects of this tumour. Primary signet ring cell carcinoma of gall bladder shows dysplastic surface gall bladder epithelium with infiltration of gall bladder wall. It is also necessary to exclude benign signet ring change, which sometimes occurs in the gall bladder. However, it is always confined to the mucosa and does not infiltrate the wall. This case showed grossly diffuse thickening of the gall bladder wall and dysplastic surface epithelium of the gall bladder on histology, with sheets of signet ring cells infiltrating full thickness of the wall. It is also necessary to exclude benign signet ring cell change, which sometimes occurs in the gall bladder. However it is always confined to the mucosa and does not infiltrate the wall. PMID- 22778191 TI - Clinical safety of 1500 mg oral naltrexone overdose. AB - This case represents a clinical overdose of the largest known dose of oral naltrexone, equivalent to the taking of a whole bottle of the oral naltrexone preparation. The patient's intention was to control craving for alcohol and opiates. The patient quickly settled with expectant management. As such it demonstrates that earlier concerns that have been voiced in this area, particularly relating to naltrexone-related hepatotoxicity and depression, may have been overstated, at least in the experience of this patient. This patient's course was marked only by gastric irritation, of which she had some history. As such the present profile provides case report evidence consistent with more robust views of the patient safety of naltrexone itself, and opposing more cautious views. Her polydrug craving was suppressed for a period of 2 weeks, which raises the important question of the mechanism of action of naltrexone's generalised suppression of refractory hedonic consumptive addictive behaviours. PMID- 22778192 TI - Massive haematemesis due to strangulated gangrenous gastric herniation as the delayed presentation of post-traumatic diaphragmatic rupture. AB - Diaphragmatic injuries are quite uncommon and often result from either blunt or penetrating trauma. Diaphragmatic ruptures are usually associated with abdominal trauma; however, it can occur in isolation. Acute traumatic rupture of the diaphragm may go unnoticed and there is often a delay between the injury and the diagnosis. Patients present with non-specific symptoms and may complain of chest pain, abdominal pain, dyspnoea, tachypnoea and cough, heartburn and symptoms of gastro-oesophageal reflux. Respiratory distress and faeco-pneumothorax have been reported. We present an interesting case of traumatic diaphragmatic hernia presenting 5 years after a road traffic accident as acute abdomen and massive haematemesis due to strangulated gangrenous gastric hernia. PMID- 22778193 TI - Giant mesenteric lymphangioma: a rare cause of a life-threatening complication in an adult. AB - Mesenteric cyst lymphangiomas (MCLs) are rare benign tumours of unknown aetiology seen mostly in children. Clinical presentation can be diverse ranging from incidental abdominal cysts to an acute abdomen. A 24-year-old previously fit and healthy young man presented with a 2-week history of cramping, central abdominal pain and vomiting requiring acute hospital admission. He was a diagnostic conundrum despite extensive preoperative investigations. Recurring symptoms required urgent surgical exploration, resection and histological confirmation with a successful outcome. We review the literature and present here this rare case in an adult of MCL that has the potential to grow, invade and develop major life-threatening complications. PMID- 22778194 TI - Hydatid cysts of the lung. AB - Cystic hydatid disease is a zoonosis caused by infection with the larval cysts of Echinococcus granulosus. Cysts commonly develop in the liver and lungs. Diagnosis in non-endemic regions is often delayed due to a failure to consider hydatidosis. This results from a non-specific presentation and a failure to record an accurate geographical history. The diagnosis requires integrating an appropriate index of suspicion with correct interpretation of imaging and serological tests. In our case, a 44-year-old woman of Yemeni origin presented to a UK hospital with chest pain, pruritus and weight loss. Following detection of pulmonary nodules, a CT guided biopsy was carried out to exclude malignancy. Iatrogenic cyst rupture precipitated an acute eosinophilic pleurisy. Cystic hydatid disease was subsequently diagnosed following strongly positive hydatid serological tests. This case illustrates the importance of considering diagnoses appropriate to an individual's geographical history particularly in the context of rising immigration and foreign travel. PMID- 22778195 TI - 'I saved a life': a heroin addict's reflections on managing an overdose using 'take home naloxone'. AB - Research shows that most heroin addicts, at some point in their drug using careers, accidentally overdose and that accidental overdose is the most common cause of death in this group. As most such overdoses are witnessed by other drug users or their carers, it is argued that providing 'take home naloxone' (a fast acting opiate antagonist) to them (as potential witnesses to an overdose) can save lives. Despite the robust evidence base to support the feasibility and effectiveness of this strategy, its integration into clinical practice in the UK is still very limited. Here, we report the case of a heroin addict who used his take home naloxone to manage an overdose and thereby saved a life. Through this account, we hope to raise clinicians' awareness of this simple yet life-saving intervention. We will also briefly discuss the evidence base for take home naloxone with particular reference to the UK and will also give some practical guidance to clinicians on prescribing take home naloxone. PMID- 22778196 TI - Port site necrotising fasciitis following laparoscopic appendicectomy. AB - Necrotising fasciitis is a fast-spreading infection affecting the fascia and, with continued spread, causes secondary necrosis of the skin. A case has been previously described in association with laparoscopic appendicectomy but with a fatal outcome. We report a similar but successfully managed case and review the literature. PMID- 22778197 TI - Haemoptysis from an innominate artery aneurysm. PMID- 22778198 TI - Diabetes, metformin use, and colon cancer: a population-based cohort study in Taiwan. AB - OBJECTIVE: A retrospective cohort study, using a population-based reimbursement database, was conducted for investigating the relationship between diabetes and colon cancer and assessing whether metformin had a protective effect. METHODS: Overall, 493,704 men and 502,139 women, covered by the National Health Insurance, without colon cancer were followed from 2003 to 2005. Cox regression evaluated the adjusted relative risk (RR), considering confounders and detection examinations. RESULTS: Even though diabetes patients had a significantly higher probability of receiving examinations that could lead to the detection of colon cancer, they had a significantly higher risk (24%) of this cancer after adjustment. Metformin users had a significantly lower risk (27%) of colon cancer. While comparing patients with diabetes for <1, 1-3, and >= 3 years to nondiabetes individuals, the adjusted RR (95% confidence interval) was 1.308 (1.020-1.679), 1.087 (0.900-1.313), and 1.185 (1.055-1.330) respectively. The higher risk among those with diabetes for <1 year suggested a possible reverse causality or a link with prediabetes. However, diabetes still might play some role in the development of colon cancer in those with diabetes for >= 3 years. The duration of metformin use showed an inverse trend, with a significant RR of 0.643 (0.490-0.845) in users for >= 3 years, when compared with nonusers. In addition, metformin may reduce colon cancer risk associated with chronic obstructive pulmonary disease (a surrogate for smoking). CONCLUSIONS: Following adjustment for potential detection bias and other covariates, diabetes remains a significant risk factor for colon cancer. Metformin may protect against colon cancer. PMID- 22778199 TI - Chiral analysis of methadone and its main metabolite, EDDP, in postmortem brain and blood by automated SPE and liquid chromatography-mass spectrometry. AB - We developed a method based on liquid chromatography coupled with tandem mass spectrometry to quantify individual enantiomers of methadone and its primary metabolite, R/S-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium (EDDP), in postmortem blood and brain tissue. Samples were prepared with a Tecan Evo robotic system. Precipitation was followed by solid-phase extraction, evaporation and reconstitution in the mobile phase. Enantiomers were fully separated with liquid chromatography on a chiral alpha(1)-acid glycoprotein column. A Quattro micro mass spectrometer was used for detection in the positive ion mode with an electrospray source. The lower limit of quantification in brain tissue was 0.005 mg/kg for methadone and 0.001 mg/kg for EDDP enantiomers; the maximum precision was 17% for both compounds; accuracy ranged from 94 to 101%. In blood, the limit of quantification was 0.001 mg/kg for all compounds, the total relative standard deviation was <15%, and the accuracy varied from 95 to 109%. Brain (n = 11) and blood (n = 15) samples were analyzed with intermediate precision that varied from 7.5 to 15% at 0.005 mg/kg and from 6.8 to 11.3% at 0.25 mg/kg for all compounds. Method development focused on producing a clean extract, particularly from brain samples. The method was tested on authentic brain and femoral blood samples. PMID- 22778200 TI - Hyponatraemia associated rhabdomyolysis following water intoxication. AB - A young man with bipolar disorder was admitted in a coma. Cerebral oedema secondary to severe hyponatraemia was implicated. This was due to self-induced water intoxication. He developed rhabdomyolysis, a massive creatine kinase (out of proportion to longstanding antipsychotic medication) and acute renal failure. In the intensive care unit, hyponatraemia was corrected, and following appropriate fluid resuscitation, with forced alkaline diuresis, the rhabdomyolysis and renal function normalised, averting renal support. While a full recovery ensued, the persisting risk factors for hyponatraemia, that is polydipsia, and its association with rhabdomyolysis, increased the chances of a recurrence. Closely supervised regulation of his water intake, and monitoring of antipsychotic efficacy (for biochemical homeostatsis) are essential for secondary prevention. Rhabdomyolysis is a rare complication of hyponatraemia. When associated with psychogenic polydipsia, the acute and chronic management are challenging. Vaptans, which are aquaretics, that preferentially prevent renal tubular water reabsorption, may be beneficial in this situation. PMID- 22778201 TI - Mesothelial cyst of the spleen in an adult: a case report. AB - A young adult in her third decade presented with a 2-week history of catching left upper abdominal pain and was detected to have a cystic lesion occupying almost the entire spleen. Laparoscopic total splenectomy was carried out, and the cyst wall revealed a true mesothelial cyst with no squamous metaplasia. The various aspects of mesothelial cysts, including immunophenotyping and treatment modalities, are briefly discussed. PMID- 22778202 TI - The (re)generation of splenic tissue. AB - A 48-year-old man with a history of a traumatic splenic rupture followed by splenectomy at the age of 5 years was referred to the outpatient clinic with markedly elevated liver enzymes. He was diagnosed with alcoholic liver cirrhosis. Ultrasound of the upper abdomen revealed hepatomegaly and suggested a central mass in the liver. Subsequent MRI of the abdomen did not show a hepatic mass, but revealed multiple intraperitoneal and retroperitoneal ovoid structures with a maximum diameter of 3 cm. A peripheral blood smear did not reveal Howell-Jolly bodies suggesting intact splenic function. The diagnosis splenosis-that is, autotransplantation of splenic tissue after iatrogenic/traumatic rupture of the spleen-was considered and confirmed by SPECT-CT with technetium-99m ((99m)Tc) labelled heat-denatured autologous red blood cells. PMID- 22778203 TI - Autosomal recessive polycystic kidney disease: the importance of autopsy of suspected cases and genetic counselling. AB - Autosomal recessive polycystic kidney disease (ARPKD) is a common inheritable cystic renal disease that has a profound effect on the growing fetus and on subsequent pregnancies, being fatal in 30% to 50% cases in the neonatal period. Prenatal imaging studies are only suggestive of the disorder and it is evident only from the second trimester onwards. Prenatal molecular linkage analysis can identify the disorder, but have a prerequisite of previous DNA analysis of parents and one sibling. ARPKD can be accurately diagnosed on characteristic histopathological features if an autopsy is performed in cases of infant death where the prenatal imaging studies and clinical findings are suggestive of the disease. A case of the characteristic histopathological findings of ARPKD on autopsy of a live-born neonate who died shortly after birth, with prenatal ultrasonographic findings suggestive of renal cystic disease, is presented. PMID- 22778204 TI - Arthroscopic identification of iliopubic and ilioischial grooves in a single adult acetabulum. AB - We report the arthroscopic identification of combined morphological variants of the acetabulum in an adult. The combination of iliopubic and ilioischial grooves has not been reported before. Preoperative radiographic and MRI failed to detect the lesions. These grooves strongly suggest incomplete fusion between the three limbs of the triradiate cartilage. When identified, this condition should not be treated as pathological but as a rare anatomical variant. Hip arthroscopy is a competent tool in discovering such asymptomatic cartilage abnormalities and subtle anatomical variations even in the presence of normal preoperative imaging. PMID- 22778205 TI - Nasendoscopy for unusual nasal symptoms. AB - A 20-year-old woman who was fit and well presented with a history of left nasal blockage for 2 years. She was noted on anterior rhinoscopy to have nasal septal deviation towards the left. She was listed for septoplasty with the aim of relieving nasal obstruction. At operation she was found to have a mildly deviated septum to the left. There was also a rhinolith in the left nostril posterior to the deviated septum (figure 1). Following removal of the rhinolith, her nasal airway appeared adequate; hence, septoplasty was not performed. Postoperatively, the patient was pleased with the outcome. When the patient was shown the foreign body she recalled inserting a pen cover into her nose about 10 years previously (figure 2). When she presented to the Accident and Emergency department at that time she was told that there was no foreign body in her nose. PMID- 22778206 TI - Management of acute-onset and life-threatening respiratory distress of unusual aetiology. AB - A 30-year-old female experienced severe acute respiratory distress in her apartment assumed to be due to an allergic asthma. Upon arrival of the emergency physician at the scene the patient was unconscious and cyanotic. Auscultation yielded no respiratory sounds despite visible efforts of the patient. Mask ventilation was virtually impossible. Endotracheal intubation was performed but complicated by a distinct resistance. Ventilation remained difficult, despite antiobstructive medication and deep general anaesthesia. Fiberoptic bronchoscopy in the hospital finally showed a bulk of granulomatous tissue located just above the tracheal bifurcation. Here, the authors report a rare case of acute-onset respiratory distress due to Wegener's granulomatosis. PMID- 22778207 TI - Fowler's syndrome and pregnancy. AB - We present a favourable outcome of a pregnant woman with underlying Fowler's syndrome. This is a rare disorder affecting young women with painless urinary retention, and as there is no known cure, the main concern is to ensure adequate bladder emptying. Our patient went through self-catheterisation and suprapubic catheters after which she was finally successfully managed on a sacral nerve stimulator (SNS). Upon getting pregnant the stimulator was switched off due to safety concerns, and from then on, bladder emptying was managed with a suprapubic catheter (which was regularly changed over the gestation). The main concern thereafter was recurrent hospital admissions with urinary tract infections and pelvic pain requiring parenteral antibiotics and analgesia. She underwent an uncomplicated elective caesarean section at 36 weeks and delivered a healthy female infant. The SNS was successfully reactivated in the postnatal phase, and the suprapubic catheter was removed upon achieving adequate urethral output. PMID- 22778208 TI - Accidental ingestion of a cocktail stick. AB - Cocktail stick (CS) ingestion injury has rarely been reported in the literature. It is a serious clinical problem with considerable morbidity and mortality, largely due to the fact that the event is unnoticed by the patient. We report a case of CS ingestion that went unrecognised by the patient and caused a perforation in the mid-small bowel. We discuss how injuries from such events can become a diagnostic challenge. The history should be re-evaluated in any undiagnosed abdominal pain which has an unclear aetiology and negative radiology. PMID- 22778209 TI - Multi-territory ischaemic strokes and subacute bacterial endocarditis. AB - We describe an elderly patient presenting with cardio-embolic stroke who was found to have infective endocarditis (IE) affecting the mitral valve. Penicillin resistant Facklamia hominis was identified as the causative pathogen. Despite initiation of aggressive antibiotic treatment, the patient suffered a fatal myocardial infarction 2 days post-diagnosis of IE. Facklamia spp. have not been previously reported to be associated with IE. Here, we discuss the link between IE and cardio-embolic stroke along with a discussion of various causative pathogens. PMID- 22778210 TI - Onset of neuropsychiatric symptoms after psychological trauma may result in erroneous diagnostic bias. AB - We report a case of neuroacanthocytosis, which was misdiagnosed as conversion disorder. Because the onset was after a psychologically stressful physical trauma, the patient's symptoms were interpreted in terms of psychological regression. The case clearly points out the defects of descriptive psychiatric diagnosis, especially in the area of somatoformal disorders. It also reminds the clinicians to keep in mind rare neurological disorders as possible causes for psychiatric symptoms. PMID- 22778211 TI - Henoch-Schonlein purpura: a clinical case with dramatic presentation. AB - A case study involving a 55-year-old Caucasian male with end-stage glomerulosclerosis is presented here. Kidney biopsies showed no deposits on imunofluorescent microscopy. Relapsing massive haemoptysis and suspected bronchovascular malformation required lung lobectomy which revealed malformative and tortuous small blood vessels, with no vasculitis. Blood antinuclear antibodies, antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies were undetectable. Seric immunoglobulins and complement levels were normal. Three months later, arthralgia and joint oedema first appeared. Skin biopsy revealed vasculitis immune-reactive to immunoglobulin A. Systemic corticotherapy was then started. Two weeks later, the patient presented with abdominal pain melena and rectal bleeding (haematoquesia). Endoscopic study showed diffuse gastrointestinal haemorrhage. Angiographic study revealed diffuse lesions compatible with vasculitis and haemorrhage from multiple spots. Cyclophosphamide and then intravenous immunoglobulin were associated to treatment without response. Increasing blood loss occurred, with massive gastrointestinal haemorrhage and haemorrhagic ascitis. Death occurred due to uncontrolled diffuse bleeding. Necropsy findings showed generalised small vessels vasculitis compatible with Henoch-Schonlein purpura. PMID- 22778212 TI - Metformin inhibits human androgen production by regulating steroidogenic enzymes HSD3B2 and CYP17A1 and complex I activity of the respiratory chain. AB - Metformin is treatment of choice for the metabolic consequences seen in polycystic ovary syndrome for its insulin-sensitizing and androgen-lowering properties. Yet, the mechanism of action remains unclear. Two potential targets for metformin regulating steroid and glucose metabolism are AMP-activated protein kinase (AMPK) signaling and the complex I of the mitochondrial respiratory chain. Androgen biosynthesis requires steroid enzymes 17alpha-Hydroxylase/17,20 lyase (CYP17A1) and 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2), which are overexpressed in ovarian cells of polycystic ovary syndrome women. Therefore, we aimed to understand how metformin modulates androgen production using NCI-H295R cells as an established model of steroidogenesis. Similar to in vivo situation, metformin inhibited androgen production in NCI cells by decreasing HSD3B2 expression and CYP17A1 and HSD3B2 activities. The effect of metformin on androgen production was dose dependent and subject to the presence of organic cation transporters, establishing an important role of organic cation transporters for metformin's action. Metformin did not affect AMPK, ERK1/2, or atypical protein kinase C signaling. By contrast, metformin inhibited complex I of the respiratory chain in mitochondria. Similar to metformin, direct inhibition of complex I by rotenone also inhibited HSD3B2 activity. In conclusion, metformin inhibits androgen production by mechanisms targeting HSD3B2 and CYP17-lyase. This regulation involves inhibition of mitochondrial complex I but appears to be independent of AMPK signaling. PMID- 22778213 TI - Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity. AB - Menopause promotes central obesity, adipose tissue (AT) inflammation, and insulin resistance (IR). Both obesity and the loss of estrogen can activate innate and adaptive immune cells (macrophages, T cells). The respective impacts of weight gain and loss of ovarian hormones on AT inflammation and IR are poorly understood. Here we determined the temporal kinetics of fat accretion, AT inflammation, and IR over a 26-wk time course in ovariectomized (OVX) mice, a model of menopause. OVX and sham-operated (SHM) C57BL6 mice were fed a normal chow diet. Weight, body composition (magnetic resonance imaging), total and regional adiposity, activity, food intake, AT crown-like structures, biohumoral measures, and insulin sensitivity (insulin tolerance testing and homeostatic model assessment) were determined at wk 12, 20, and 26. Macrophages and T cells from perigonadal AT were immunophenotyped by fluorescence-associated cell sorting, and perigonadal adipose tissue (PGAT) gene expression was quantified by quantitative PCR. OVX mice (~ 31 g) became fatter than SHM mice (~ 26 g) by wk 12, but mice were equally insulin sensitive. PGAT of OVX mice contained more T cells but expressed higher levels of M2-MPhi (arginase-1) and T cell-regulatory (cytotoxic T-lymphocyte antigen 4) genes. At wk 20, both OVX and SHM mice weighed approximately 35 g and were equally insulin sensitive with comparable amounts of PGAT and total body fat. OVX mice became less insulin sensitive than SHM mice by wk 26, coincident with the down-regulation of PGAT arginase-1 (-20-fold) and cytotoxic T-lymphocyte antigen 4 (2-fold) and up-regulation of M1/Th1 genes CD11c (+2-fold), IL12p40 (+2-fold), and interferon-gamma (+78-fold). Ovarian hormone loss in mice induces PGAT inflammation and IR by mechanisms that can be uncoupled from OVX-induced obesity. PMID- 22778214 TI - TNF-alpha represses beta-Klotho expression and impairs FGF21 action in adipose cells: involvement of JNK1 in the FGF21 pathway. AB - Fibroblast growth factor 21 (FGF21) is a member of the FGF family that reduces glycemia and ameliorates insulin resistance. Adipose tissue is a main target of FGF21 action. Obesity is associated with a chronic proinflammatory state. Here, we analyzed the role of proinflammatory signals in the FGF21 pathway in adipocytes, evaluating the effects of TNF-alpha on beta-Klotho and FGF receptor-1 expression and FGF21 action in adipocytes. We also determined the effects of rosiglitazone on beta-Klotho and FGF receptor-1 expression in models of proinflammatory signal induction in vitro and in vivo (high-fat diet-induced obesity). Because c-Jun NH(2)-terminal kinase 1 (JNK1) serves as a sensing juncture for inflammatory status, we also evaluated the involvement of JNK1 in the FGF21 pathway. TNF-alpha repressed beta-Klotho expression and impaired FGF21 action in adipocytes. Rosiglitazone prevented the reduction in beta-Klotho expression elicited by TNF-alpha. Moreover, beta-Klotho levels were reduced in adipose tissue from high-fat diet-induced obese mice, whereas rosiglitazone restored beta-Klotho to near-normal levels. beta-Klotho expression was increased in white fat from JNK1(-/-) mice. The absence of JNK1 increased the responsiveness of mouse embryonic fibroblast-derived adipocytes and brown adipocytes to FGF21. In conclusion, we show that proinflammatory signaling impairs beta-Klotho expression and FGF21 responsiveness in adipocytes. We also show that JNK1 activity is involved in modulating FGF21 effects in adipocytes. The impairment in the FGF21 response machinery in adipocytes and the reduction in FGF21 action in response to proinflammatory signals may play important roles in metabolic alterations in obesity and other diseases associated with enhanced inflammation. PMID- 22778215 TI - The role of anti-Mullerian hormone (AMH) during follicle development in a monovulatory species (sheep). AB - Knockout studies in mice have suggested that anti-Mullerian hormone (AMH) modulates primordial follicle recruitment and the response of growing follicles to FSH. Little is known of the physiology of AMH in monovular species, despite intense clinical interest in this factor. Using sheep as a model, we sought to investigate the functional role of AMH in modulating follicle development in monovular species. In contrast to the rodent, the results indicate that AMH does not affect the rate of primordial follicle recruitment but appears to regulate the rate at which follicles progress through the gonadotropin-responsive phase, during which it is maximally expressed. Thus, knockdown of AMH bioactivity by active immunization lead to a decline in the population of gonadotropin responsive preantral and small antral follicles (P < 0.01) and increases in both the number of gonadotropin-dependent antral follicles (P < 0.01) and ovulation rate (P < 0.05). These in vivo findings were consistent with the results of other studies examining the pattern of expression of AMH, which was negatively correlated with aromatase (P < 0.001), and in vitro supplementation experiments, which supported an inhibitory role for AMH in modulating the response of both theca and granulosa cells to LH and FSH, respectively. The elucidation of a functional relationship between AMH and LH-stimulated thecal androgen production may be significant in terms of the etiology of common forms of anovulatory infertility in women. Furthermore, the observed increase in both the number of recruitable antral follicles and ovulatory quota in response to AMH knockdown may have therapeutic value in women who respond poorly to ovarian stimulation. PMID- 22778216 TI - Distribution and estrogen regulation of membrane progesterone receptor-beta in the female rat brain. AB - Although several studies have reported the localization of membrane progesterone (P(4)) receptors (mPR) in various tissues, few have attempted to describe the distribution and regulation of these receptors in the brain. In the present study, we investigated expression of two mPR subtypes, mPRalpha and mPRbeta, within regions of the brain, known to express estradiol (E(2))-dependent [preoptic area (POA) and hypothalamus] and independent (cortex) classical progestin receptors. Saturation binding and Scatchard analyses on plasma membranes prepared from rat cortex, hypothalamus, and POA demonstrated high affinity, specific P(4)-binding sites characteristic of mPR. Using quantitative RT-PCR, we found that mPRbeta mRNA was expressed at higher levels than mPRalpha, indicating that mPRbeta may be the primary mPR subtype in the rat brain. We also mapped the distribution of mPRbeta protein using immunohistochemistry. The mPRbeta-immunoreactive neurons were highly expressed in select nuclei of the hypothalamus (paraventricular nucleus, ventromedial hypothalamus, and arcuate nucleus), forebrain (medial septum and horizontal diagonal band), and midbrain (oculomotor and red nuclei) and throughout many areas of the cortex and thalamus. Treatment of ovariectomized female rats with E(2) benzoate increased mPRbeta immunoreactivity within the medial septum but not the medial POA, horizontal diagonal band, or oculomotor nucleus. Together, these findings demonstrate a wide distribution of mPRbeta in the rodent brain that may contribute to functions affecting behavioral, endocrine, motor, and sensory systems. Furthermore, E(2) regulation of mPRbeta indicates a mechanism through which estrogens can regulate P(4) function within discrete brain regions to potentially impact behavior. PMID- 22778218 TI - Glucocorticoids modulate the mTOR pathway in the hippocampus: differential effects depending on stress history. AB - Glucocorticoid (GC) hormones, released by the adrenals in response to stress, are key regulators of neuronal plasticity. In the brain, the hippocampus is a major target of GC, with abundant expression of the GC receptor. GC differentially affect the hippocampal transcriptome and consequently neuronal plasticity in a subregion-specific manner, with consequences for hippocampal information flow and memory formation. Here, we show that GC directly affect the mammalian target of rapamycin (mTOR) signaling pathway, which plays a central role in translational control and has long-lasting effects on the plasticity of specific brain circuits. We demonstrate that regulators of the mTOR pathway, DNA damage-induced transcript (DDIT)4 and FK506-binding protein 51 are transcriptionally up regulated by an acute GC challenge in the dentate gyrus (DG) subregion of the rat hippocampus, most likely via a GC-response element-driven mechanism. Furthermore, two other mTOR pathway members, the mTOR regulator DDIT4-like and the mTOR target DDIT3, are down-regulated by GC in the rat DG. Interestingly, the GC responsiveness of DDIT4 and DDIT3 was lost in animals with a recent history of chronic stress. Basal hippocampal mTOR protein levels were higher in animals exposed to chronic stress than in controls. Moreover, an acute GC challenge significantly reduced mTOR protein levels in the hippocampus of animals with a chronic stress history but not in unstressed controls. Based on these findings, we propose that direct regulation of the mTOR pathway by GC represents an important mechanism regulating neuronal plasticity in the rat DG, which changes after exposure to chronic stress. PMID- 22778217 TI - Progesterone increases the release of brain-derived neurotrophic factor from glia via progesterone receptor membrane component 1 (Pgrmc1)-dependent ERK5 signaling. AB - Progesterone (P4) is cytoprotective in various experimental models, but our understanding of the mechanisms involved is still incomplete. Our laboratory has implicated brain-derived neurotrophic factor (BDNF) signaling as an important mediator of P4's protective actions. We have shown that P4 increases the expression of BDNF, an effect mediated by the classical P4 receptor (PR), and that the protective effects of P4 were abolished using inhibitors of Trk receptor signaling. In an effort to extend our understanding of the interrelationship between P4 and BDNF signaling, we determined whether P4 influenced BDNF release and examined the role of the classical PR and a putative membrane PR, progesterone receptor membrane component-1 (Pgrmc1), as mediators of this response. Given recent data from our laboratory that supported the role of ERK5 in BDNF release, we also tested whether P4-induced BDNF release was mediated by ERK5. In this study, we found that P4 and the membrane-impermeable P4 (P4-BSA) both induced BDNF release from cultured C6 glial cells and primary astrocytes. Both these cells lack the classical nuclear/intracellular PR but express high levels of membrane-associated PR, including Pgrmc1. Using RNA interference mediated knockdown of Pgrmc1 expression, we determined that P4-induced BDNF release was dependent on the expression of Pgrmc1, although pharmacological inhibition of the PR failed to alter the effects of P4. Furthermore, the BDNF release elicited by P4 was mediated by ERK5, and not ERK1/2. Collectively, our data describe that P4 elicits an increase in BDNF release from glia via a Pgrmc1 induced ERK5 signaling mechanism and identify Pgrmc1 as a potential therapeutic target for future hormone-based drug development for the treatment of such degenerative diseases as Alzheimer's disease as well as other diseases wherein neurotrophin dysregulation is noted. PMID- 22778220 TI - Pax6 is a key component of regulated glucagon secretion. AB - The Pax6 transcription factor is crucial for pancreatic alpha-cells. Indeed, Pax6 deficient mouse models are characterized by markedly altered alpha-cell differentiation. Our objective was to investigate the role of Pax6 in glucagon secretion process. We used a Pax6-deficient model in rat primary enriched-alpha cells with specific small interfering RNA leading to a 70% knockdown of Pax6 expression. We first showed that Pax6 knockdown decreases glucagon biosynthesis as well as glucagon release. Through physiological assays, we demonstrated that the decrease of Pax6 affects specifically acute glucagon secretion in primary alpha-cell in response to glucose, palmitate, and glucose-dependent insulinotropic peptide (GIP) but not the response to arginine and epinephrine. We identified in Pax6 knockdown model that genes involved in glucagon secretion such as the glucokinase (GCK), G protein-coupled receptor (GPR40), and GIP receptor (GIPR) as well as the corresponding proteins were significantly decreased whereas the insulin receptor (IR) Kir6.2/Sur1, and glucose transporter 1 genes were not affected. We demonstrated that Pax6 directly binds and activates specific elements on the promoter region of the GPR40, GCK, and GIPR genes. Finally, through site-directed mutagenesis experiments, we showed that disruption of Pax6 binding on the GCK, GPR40, and GIPR gene promoters led to specific decreases of their activities in the alphaTC1.9 glucagon-producing cell line. Hence our results indicate that Pax6 acts on the regulation of glucagon secretion at least through the transcriptional control of GCK, GPR40, and GIPR. We propose that Pax6 is not only critical for glucagon biosynthesis but also for glucagon secretion particularly in response to nutrients. PMID- 22778219 TI - Brain meets body: the blood-brain barrier as an endocrine interface. AB - The blood-brain barrier (BBB) separates the central nervous system (CNS) from the peripheral tissues. However, this does not prevent hormones from entering the brain, but shifts the main control of entry to the BBB. In general, steroid hormones cross the BBB by transmembrane diffusion, a nonsaturable process resulting in brain levels that reflect blood levels, whereas thyroid hormones and many peptides and regulatory proteins cross using transporters, a saturable process resulting in brain levels that reflect blood levels and transporter characteristics. Protein binding, brain-to-blood transport, and pharmacokinetics modulate BBB penetration. Some hormones have the opposite effect within the CNS than they do in the periphery, suggesting that these hormones cross the BBB to act as their own counterregulators. The cells making up the BBB are also endocrine like, both responding to circulating substances and secreting substances into the circulation and CNS. By dividing a hormone's receptors into central and peripheral pools, the former of which may not be part of the hormone's negative feed back loop, the BBB fosters the development of variable hormone resistance syndromes, as exemplified by evidence that altered insulin action in the CNS can contribute to Alzheimer's disease. In summary, the BBB acts as a regulatory interface in an endocrine-like, humoral-based communication between the CNS and peripheral tissues. PMID- 22778221 TI - Hypothalamic CB1 cannabinoid receptors regulate energy balance in mice. AB - Cannabinoid type 1 (CB(1)) receptor activation is generally considered a powerful orexigenic signal and inhibition of the endocannabinoid system is beneficial for the treatment of obesity and related metabolic diseases. The hypothalamus plays a critical role in regulating energy balance by modulating both food intake and energy expenditure. Although CB(1) receptor signaling has been implicated in the modulation of both these mechanisms, a complete understanding of its role in the hypothalamus is still lacking. Here we combined a genetic approach with the use of adeno-associated viral vectors to delete the CB(1) receptor gene in the adult mouse hypothalamus and assessed the impact of such manipulation on the regulation of energy balance. Viral-mediated deletion of the CB(1) receptor gene in the hypothalamus led to the generation of Hyp-CB(1)-KO mice, which displayed an approximately 60% decrease in hypothalamic CB(1) receptor mRNA levels. Hyp-CB(1) KO mice maintained on a normocaloric, standard diet showed decreased body weight gain over time, which was associated with increased energy expenditure and elevated beta(3)-adrenergic receptor and uncoupling protein-1 mRNA levels in the brown adipose tissue but, surprisingly, not to changes in food intake. Additionally, Hyp-CB(1)-KO mice were insensitive to the anorectic action of the hormone leptin (5 mg/kg) and displayed a time-dependent hypophagic response to the CB(1) inverse agonist rimonabant (3 mg/kg). Altogether these findings suggest that hypothalamic CB(1) receptor signaling is a key determinant of energy expenditure under basal conditions and reveal its specific role in conveying the effects of leptin and pharmacological CB1 receptor antagonism on food intake. PMID- 22778222 TI - Effect of food restriction and leptin supplementation on fetal programming in mice. AB - Metabolic disease is a significant global health and economic problem. In a phenomenon referred to as fetal programming, offspring of underweight or overweight mothers have an increased incidence of adulthood obesity and metabolic disease. Undernourished individuals have decreased levels of leptin, a regulator of energy balance, whereas obese people develop hyperleptinemia and leptin resistance. We hypothesize that alterations in circulating leptin during pregnancy contribute to programming events caused by maternal nutritional status. To test this hypothesis, pregnant mice were randomly placed in one of three treatment groups: ad libitum feed plus saline injection (control, n = 5), 50% food restriction plus saline injection (restricted, n = 4), or 50% food restriction plus 1 mg/kg . d leptin injection (restricted, leptin treated, n = 4). Mice were treated from 1.5 to 11.5 d after conception and then returned to ad libitum feeding until weaning. At 19 wk after weaning, offspring were placed on a 45% fat diet and then followed up until 26 wk after weaning, at which time they were killed, and samples were collected for further analysis. Our results demonstrate that males are more negatively impacted by high-fat diet than females, regardless of maternal treatment. We provide evidence that differential response to leptin may mediate the sexual dimorphism observed in fetal programming in which male offspring are more affected by maternal undernutrition and female offspring by maternal overnutrition. We show that female offspring born to food-restricted, leptin-supplemented mothers are obese and insulin resistant. This may mimic fetal programming events seen in offspring of overweight women. PMID- 22778223 TI - Differentiation of human embryonic stem cells and human induced pluripotent stem cells into steroid-producing cells. AB - Although there have been reports of the differentiation of mesenchymal stem cells and mouse embryonic stem (ES) cells into steroid-producing cells, the differentiation of human ES/induced pluripotent stem (iPS) cells into steroid producing cells has not been reported. The purpose of our present study was to establish a method for inducing differentiation of human ES/iPS cells into steroid-producing cells. The first approach we tried was embryoid body formation and further culture on adherent plates. The resultant differentiated cells expressed mRNA encoding the steroidogenic enzymes steroidogenic acute regulatory protein, 3beta-hydroxysteroid dehydrogenase, cytochrome P450-containing enzyme (CYP)-11A1, CYP17A1, and CYP19, and secreted progesterone was detected in the cell medium. However, expression of human chorionic gonadotropin was also detected, suggesting the differentiated cells were trophoblast like. We next tried a multistep approach. As a first step, human ES/iPS cells were induced to differentiate into the mesodermal lineage. After 7 d of differentiation induced by 6-bromoindirubin-3'-oxime (a glycogen synthase kinase-3beta inhibitor), the human ES/iPS cells had differentiated into fetal liver kinase-1- and platelet derived growth factor receptor-alpha-expressing mesodermal lineage cells. As a second step, plasmid DNA encoding steroidogenic factor-1, a master regulator of steroidogenesis, was introduced into these mesodermal cells. The forced expression of steroidogenic factor-1 and subsequent addition of 8-bromoadenosine 3',5'-cyclic monophosphate induced the mesodermal cells to differentiate into the steroidogenic cell lineage, and expression of CYP21A2 and CYP11B1, in addition to steroidogenic acute regulatory protein, 3beta-hydroxysteroid dehydrogenase, CYP11A1, and CYP17A1, was detected. Moreover, secreted cortisol was detected in the medium, but human chorionic gonadotropin was not. These findings indicate that the steroid-producing cells obtained through the described multistep method are not trophoblast like; instead, they exhibit characteristics of adrenal cortical cells. PMID- 22778224 TI - Estradiol treatment and hormonal fluctuations during the estrous cycle modulate the expression of estrogen receptors in the auditory system and the prepulse inhibition of acoustic startle response. AB - Estrogens' effects on hearing are documented across species, but the responsible molecular mechanisms remain unknown. The presence of estrogen receptors (ER) throughout the auditory system offers a potential pathway of direct estrogenic effects on auditory function, but little is known about how each ER's expression is regulated by the overall hormonal status of the body. In the present study, we determined the effects of ovariectomy and chronic 17beta-estradiol treatment on mRNA and protein expression of ERalpha and ERbeta in peripheral (cochlea) and central (inferior colliculus) auditory structures of mice, as well as on auditory related behavior using the acoustic startle response (ASR), prepulse inhibition (PPI), and habituation of the startle response. 17beta-Estradiol treatment down regulated ERalpha but not ERbeta and increased PPI and latency of the ASR. Neither the magnitude nor the habituation of ASR was affected. Furthermore, ER's mRNA and protein expression in the inner ear were analyzed throughout the estrous cycle (proestrus, estrus, metestrus, and diestrus), revealing a negative correlation of circulating estrogens with ERalpha expression, whereas ERbeta was stable. Our findings show that ER not only are present in both the peripheral and central auditory system but also that circulating estrogen levels down-regulate ERalpha expression in the auditory system and affect PPI and the latency of ASR, suggesting a key role of ERalpha as a hormone-induced modulator of the auditory system and behavior. PMID- 22778225 TI - beta-Endorphin antagonizes the effects of alpha-MSH on food intake and body weight. AB - Proopiomelanocortin (POMC) is posttranslationally processed to several peptides including alpha-MSH, a primary regulator of energy balance that inhibits food intake and stimulates energy expenditure. However, another POMC-derived peptide, beta-endorphin (beta-EP), has been shown to stimulate food intake. In this study we examined the effects of intracerebroventricular (icv) beta-EP on food intake and its ability to antagonize the negative effects of alpha-MSH on energy balance in male rats. A single icv injection of beta-EP stimulated food intake over a 2- to 6-h period during both the light and dark cycles. This effect was, however, not sustained with chronic icv beta-EP infusion. In the next study, a subthreshold dose of beta-EP was injected together with Nle(4), d-Phe(7) (NDP) MSH after a 16-h fast, and the negative effects of NDP-MSH on refeeding and body weight gain were partially reversed. Finally, peptide interactions were studied in a chronic icv infusion model. Weight gain and food intake were significantly suppressed in the NDP-MSH group during the entire study. A subthreshold dose of beta-EP antagonized these suppressive effects on food intake and weight gain for the first 3 d. However on d 4-7, beta-EP no longer blocked these effects. Of note, the stimulatory effect of beta-EP on feeding and its ability to antagonize MSH were specific for beta-EP(1-31) and were not observed with beta-EP(1-27). This study highlights the importance of understanding how the balance between alpha-MSH and beta-EP is maintained and the potential role of differential POMC processing in regulating energy balance. PMID- 22778226 TI - Minireview: Hair cortisol: a novel biomarker of hypothalamic-pituitary adrenocortical activity. AB - Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis is commonly assessed by measuring glucocorticoids such as cortisol (CORT). For many years, CORT was obtained primarily from blood plasma or urine, whereas later approaches added saliva and feces for noninvasive monitoring of HPA functioning. Despite the value of all these sample matrices for answering many research questions, they remain limited in the temporal range of assessment. Plasma and saliva are point samples that vary as a function of circadian rhythmicity and are susceptible to confounding by environmental disturbances. Even urine and feces generally assess HPA activity over a period of only 24 h or less. We and others have recently developed and validated methods for measuring the concentration of CORT in the body hair of animals (e.g. rhesus monkeys) and scalp hair of humans. CORT is constantly deposited in the growing hair shaft, as a consequence of which such deposition can serve as a biomarker of integrated HPA activity over weeks and months instead of minutes or hours. Since the advent of this methodological advance, hair CORT has already been used as an index of chronic HPA activity and stress in human clinical and nonclinical populations, in a variety of laboratory housed and wild-living animal species, and in archival specimens that are many decades or even centuries old. Moreover, because human hair is known to grow at an average rate of about 1 cm/month, several studies suggest that CORT levels in hair segments that differ in proximity to the scalp can, under certain conditions, be used as a retrospective calendar of HPA activity during specific time periods preceding sample collection. PMID- 22778228 TI - Nursing during the first two days of life is essential for the expression of proteins important for growth and remodeling of the neonatal porcine cervix. AB - The neonatal porcine cervix is sensitive to hormones, including relaxin (RLX), from birth. Whether nursing is required to establish the cervical developmental program or to determine cervical developmental trajectory is unknown. The objective of study 1 was to determine effects of age and nursing on expression of molecular markers and mediators of porcine cervical growth and remodeling from birth to postnatal day (PND) 2 and to document effects of RLX treatment during this period on expression of targeted gene products in nursed vs. replacer-fed gilts. Study 2 was conducted to determine effects of age at first nursing and duration of nursing from birth on expression of targeted transcripts or proteins at PND 14. Nursing supported cervical estrogen receptor-alpha, vascular endothelial growth factor, matrix metalloproteinase (MMP)9, and antiapoptotic B cell lymphoma-2 protein expression on PND 2. These proteins were undetectable in replacer-fed gilts. Returning replacer-fed gilts to nursing after PND 2 did not restore cervical expression of these proteins by PND 14. RLX increased (P < 0.05) cervical estrogen receptor-alpha, vascular endothelial growth factor, and B-cell lymphoma-2 protein in nursed gilts, MMP2 protein in nursed and replacer-fed gilts, and decreased (P < 0.05) pro-MMP9 protein in nursed gilts, and RXFP1 mRNA levels in nursed and replacer-fed gilts at PND 2. Replacer feeding for 2 wk from birth increased (P < 0.05) RXFP1 mRNA levels on PND 14. Results support the lactocrine hypothesis for maternal programming of neonatal tissues. Nursing from birth is required to establish the neonatal cervical developmental program and to maintain cervical developmental trajectory to PND 14. PMID- 22778227 TI - Minireview: translational animal models of human menopause: challenges and emerging opportunities. AB - Increasing importance is placed on the translational validity of animal models of human menopause to discern risk vs. benefit for prediction of outcomes after therapeutic interventions and to develop new therapeutic strategies to promote health. Basic discovery research conducted over many decades has built an extensive body of knowledge regarding reproductive senescence across mammalian species upon which to advance animal models of human menopause. Modifications to existing animal models could rapidly address translational gaps relevant to clinical issues in human menopausal health, which include the impact of 1) chronic ovarian hormone deprivation and hormone therapy, 2) clinically relevant hormone therapy regimens (cyclic vs. continuous combined), 3) clinically relevant hormone therapy formulations, and 4) windows of opportunity and optimal duration of interventions. Modifications in existing animal models to more accurately represent human menopause and clinical interventions could rapidly provide preclinical translational data to predict outcomes regarding unresolved clinical issues relevant to women's menopausal health. Development of the next generation of animal models of human menopause could leverage advances in identifying genotypic variations in estrogen and progesterone receptors to develop personalized menopausal care and to predict outcomes of interventions for protection against or vulnerability to disease. Key to the success of these models is the close coupling between the translational target and the range of predictive validity. Preclinical translational animal models of human menopause need to keep pace with changes in clinical practice. With focus on predictive validity and strategic use of advances in genetic and epigenetic science, new animal models of human menopause have the opportunity to set new directions for menopausal clinical care for women worldwide. PMID- 22778229 TI - Prenatal exposure to low levels of androgen accelerates female puberty onset and reproductive senescence in mice. AB - Sex steroid hormone production and feedback mechanisms are critical components of the hypothalamic-pituitary-gonadal (HPG) axis and regulate fetal development, puberty, fertility, and menopause. In female mammals, developmental exposure to excess androgens alters the development of the HPG axis and has pathophysiological effects on adult reproductive function. This study presents an in-depth reproductive analysis of a murine model of prenatal androgenization (PNA) in which females are exposed to a low dose of dihydrotestosterone during late prenatal development on embryonic d 16.5-18.5. We determined that PNA females had advanced pubertal onset and a delay in the time to first litter, compared with vehicle-treated controls. The PNA mice also had elevated testosterone, irregular estrous cyclicity, and advanced reproductive senescence. To assess the importance of the window of androgen exposure, dihydrotestosterone was administered to a separate cohort of female mice on postnatal d 21-23 [prepubertal androgenization (PPA)]. PPA significantly advanced the timing of pubertal onset, as observed by age of the vaginal opening, yet had no effects on testosterone or estrous cycling in adulthood. The absence of kisspeptin receptor in Kiss1r-null mice did not change the acceleration of puberty by the PNA and PPA paradigms, indicating that kisspeptin signaling is not required for androgens to advance puberty. Thus, prenatal, but not prepubertal, exposure to low levels of androgens disrupts normal reproductive function throughout life from puberty to reproductive senescence. PMID- 22778230 TI - Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease. AB - Hypertrophic cardiomyopathy (HCM) is more severe in male than female mice eating a soy-based diet. We sought to determine whether the detrimental effects are mediated by the phytoestrogens present in soy, the mechanism by which phytoestrogens act, and to test whether estrogen modulates the sexually dimorphic phenotype. A soy-free diet (casein based) supplemented with the predominant phytoestrogens in soy, genistein and daidzein, recapitulated the fibrotic, proapoptotic and negative hemodynamic effects of soy in male hearts. As with the soy diet, the hearts of female HCM mice were not negatively affected by the phytoestrogen-containing diet. To determine the role of estrogen in the sex differences mediated by diet in HCM, gonadectomies were performed and estrogen was administered to male and female HCM mice on a casein- or phytoestrogen supplemented diet. Somewhat surprisingly, estrogen was not protective in male or female mice with HCM and, in fact, was lethal in phytoestrogen-fed male mice with HCM. Because genistein is a potent tyrosine kinase inhibitor and tyrosine kinase inhibition has been associated with cardiotoxicity, we tested its effects in isolated adult cardiac myocytes. Genistein inhibited different tyrosine kinases depending on sex and, in combination with estrogen, resulted in apoptosis only in adult male cardiac myocytes. Finally, we show that phytoestrogens led to distinct programs of gene expression in hearts from males vs. females with HCM, suggesting mechanisms by which males are more sensitive to the detrimental effects of phytoestrogens and females are protected. These results implicate the phytoestrogen genistein in mediating cardiac pathology in males with HCM and, importantly, establish that estrogen is not protective in the setting of HCM. PMID- 22778231 TI - Acute myocardial infarction due to a coronary embolus during left atrial ablation for persistent atrial fibrillation. PMID- 22778232 TI - New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. AB - We provide a new classification for the neuronal ceroid lipofuscinoses (NCLs) that takes into account recent genetic and biochemical advances. This was originally developed by an international group with clinical, molecular genetic, biological, and morphologic interests, further revised by a panel of world experts in the NCLs, and is now updated in light of recent research findings. The aim is to provide young people, carers, and professionals with a diagnostic label that is informative, leads to effective clinical management of symptoms and in the future perhaps a cure, as well as aiding basic scientific and clinical research. We suggest that clinicians should aim to provide every child and family with detailed diagnostic information at clinical, biochemical, and genetic levels where possible, which the new classification allows in a gene-led hierarchical manner. The robustness and applicability of this updated new classification have been independently audited in the clinical setting using a series of patients previously diagnosed with NCL according to standard ultrastructural, biochemical, or genetic criteria. PMID- 22778233 TI - Reflections: neurology and the humanities. Not just yet. PMID- 22778234 TI - Comment: Frontal lobes, executive dysfunction, gait, and the fallacy of pseudo transitivity. PMID- 22778235 TI - Mutation in the CHAC gene in a family of autosomal dominant chorea acanthocytosis. PMID- 22778237 TI - Teaching neuroimages: neurogenic thoracic outlet syndrome. PMID- 22778238 TI - Pearls & oy-sters: osteoid osteoma of the scapula masquerading as neuralgic amyotrophy. PMID- 22778239 TI - Whole-body vibration exposure in metropolitan bus drivers. AB - BACKGROUND: Back injuries are common in transit drivers, and can result in substantial direct and indirect cost to the employer and employee. Whole-body vibration (WBV) is one risk factor for drivers. Standards have been adopted (ISO 2631-1) to guide researchers in measuring and analysing WBV levels. Lately, a new standard has been added (ISO 2631-5) that takes impulsive exposures into account. AIMS: The aims of this study were to determine the levels of vibration for bus drivers using both ISO 2631-1 and 2631-5 standards, and whether there are differences in vibration levels and seat transmissibility between different road types. METHODS: Thirteen bus drivers drove a 7-year-old bus, instrumented to measure WBV in the seat and floor. The 52 km long test route included freeway, city streets and speed humps. Additionally, for comparison, a subset of five drivers also drove a car over the same route. RESULTS: Road type had a significant effect on all the vibration parameters. Based on exposure limit values in the standards, the continuous z-A (w)(8) exposures exceeded the limit value on freeways, and the impulsive z-VDV(8) and S (ed) exposures were above limit values in city streets and speed humps. Bus WBV exposures were about twice as high relative to the car and the bus seat amplified rather than attenuated WBV exposures. CONCLUSIONS: Bus drivers are potentially being exposed to daily vibration levels higher than recommended especially on certain road types. The current seat in this study does not attenuate the vibration. PMID- 22778240 TI - Shift work effects on serial PEF measurements for occupational asthma. AB - BACKGROUND: Diurnal variation (DV) affects lung function but the changes are thought to be related to sleep patterns rather than time of day. When diagnosing occupational asthma (OA), serial peak expiratory flow (PEF) measurements are the recommended first line investigation, but could be confounded by shift work. AIMS: The aim of the study was to investigate the effects of shift work on PEF measurements used for diagnosing OA. METHODS: PEF records containing more than one shift pattern with >= 4 days per shift were identified. OA diagnosis was based on an Oasys-2 score >= 2.51 and non-OA on having an alternative clinical diagnosis and Oasys-2 score <2.51. The mean area between curves (ABC) score, mean PEF DV and cross-shift PEF changes were calculated for each shift. RESULTS: Records from 123 workers with OA and 69 without OA satisfied inclusion criteria. In the OA group, PEF declined more on afternoon and night shifts than days (P < 0.001). The ABC score was lower in the OA group on night (P < 0.05) and afternoon shifts (P < 0.05) as compared with days, without significant differences in DV. Among those without OA, cross-shift PEF increased more on day shifts (mean + 25 l/min) than afternoon or night shifts (+1 l/min) (P < 0.001). The sensitivity for the ABC score and DV were good and similar across shifts, but specificity was reduced using DV (DV mean 39%; ABC 98%). CONCLUSIONS: PEF responses between work and rest show small differences according to shift type. The ABC score has a high sensitivity and specificity for all shifts; differences in DV have lower specificity. PMID- 22778241 TI - Prevalence of knee bursitis in the workforce. AB - BACKGROUND: Knee bursitis (KB) is a common disorder in specific occupations requiring frequent and/or sustained kneeling postures. AIMS: To assess the prevalence of KB in the general working population. METHODS: Between 2002 and 2005, a total of 3710 workers of a French region were randomly included in the study. A standardized physical examination of the knee was performed when knee pain was reported by the worker during the preceding 12 months. The criteria for diagnosis of KB were (i) the presence of pain and/or tenderness in the anterior face of the knee at the date of the examination (or for at least 4 days in the preceding week) and (ii) the presence of swelling and/or pressure-induced pain of the pre- or infra-patellar bursa. Occupational risk factors were assessed by a self-administered questionnaire. RESULTS: The prevalence of uni- or bilateral cases of knee bursitis was low: 0.6% [0.2-0.9] in men and 0.2% [0.0-0.6] in women. The highest prevalence was observed in the construction sector (2.3% [0.8 5.4]) and in the food and meat processing industries (1.4% [0.4-3.5)]. More blue collar workers were affected than other occupation categories (0.8% [0.3-1.2] versus 0.1% [0.0-0.4]). CONCLUSIONS: The study showed a concentration of cases among male workers exposed to heavy workloads and frequent kneeling. PMID- 22778242 TI - Cleft palate, arachnoid cyst and posterior urethral valve. AB - A 5-month-old infant presented with cleft palate, febrile urinary tract infection and abnormal movements. His urinary stream was poor and investigations revealed posterior urethral valve and grade V vesicoureteric reflux. This baby was investigated for seizure activity and on MRI of the brain was found to have a large arachnoid cyst, splaying the occipital horns and compressing the posterior aspect of third ventricle leading to dilatation of the ventricles. This seems to be a very unusual coexistence of three abnormalities in one patient for which no plausible explanation can be given. It appears to be a chance finding. PMID- 22778243 TI - Idiopathic granulomatous mastitis: rare but important. AB - A 61-year-old woman attended the breast clinic with unresolving mastitis and an associated mass, following failed treatment with antibiotics. Triple assessment confirmed idiopathic granulomatous mastitis. Unresponsive to further conservative management and steroid therapy, she underwent surgical excision and made uneventful recovery. No evidence of recurrence was detected at 18 months follow up. PMID- 22778244 TI - Idiopathic stroke in a normal parturient. AB - A 34-year-old Chinese woman was admitted to the labour suite for induction of labour. She had no history of hypertension, vascular disease or coagulapathy. She was induced for less fetal movement at 38 weeks of gestation. Labour progressed smoothly, but immediately after delivery the patient had symptoms of facial neurological deficit, slurred speech and heaviness in the left side of the body. After completion of the third stage of labour, her condition soon deteriorated with left-sided facial palsy and left-sided dense hemiplegia. The patient was then transferred to the intensive care unit where an urgent CT scan was arranged for her. She was diagnosed as a case of right-sided stroke with dense left-sided hemiplegia and left facial palsy. She was placed under the care of the neurosurgical team for 2 weeks and was discharged on regular physiotherapy treatment. She had completely recovered 6 months later. PMID- 22778245 TI - Fistulous connection between the left anterior descending coronary artery and pulmonary artery. PMID- 22778246 TI - A happy ending in hepatomegaly. PMID- 22778247 TI - Multiple cerebral gaseous emboli in an infant with fulminant necrotising enterocolitis. PMID- 22778248 TI - Red eye in chickenpox: varicella-related acute anterior uveitis in a child. AB - Varicella-zoster virus is a common viral infection of childhood. This report concerns an 8-year-old girl who presented with a 5-day history of a typical varicella rash. She then developed red left eye 'conjunctivitis'. She had no discharge, mild pain and intense photophobia. She was referred to the acute eye clinic after 1 day and she was noted to have acute anterior uveitis. She was treated with gutt atropine 1% for 2 weeks until the inflammation resolved. She had no sequalae. PMID- 22778249 TI - Successful management of fulminant influenza A subtype H1N1 myocarditis. AB - The outbreak and spread of the new influenza A subtype H1N1 reached pandemic levels during 2009, with greater numbers of cases reported daily and numerous complications described. The present report concerns an atypical manifestation of the disease in a previously healthy middle-aged patient who presented with severe, refractory cardiogenic shock 4 days after being diagnosed as having influenza A. The patient was considered for emergency heart transplant. Successful treatment involved the use of a left ventricular assist device, extracorporeal membrane oxygenation, intravenous immunoglobulin and peramivir as therapeutics and bridging therapies for transplant. This case is a report of H1N1 fulminant myocarditis and illustrates the usefulness of a multidisciplinary approach in the care of these patients. PMID- 22778250 TI - Myxoedema madness. AB - A 59-year-old man was referred for Mental Health Act Assessment following several months of 'odd behaviour' and self-neglect reported by his neighbours. He presented as unkempt and expressed delusional ideas with respect to age, employment and identity of family members. He was fully oriented but lacked insight into his mental state and capacity for self-care. Physical examination revealed dry skin and slow relaxing reflexes. Blood investigations revealed a raised thyroid stimulating hormone and free T4 with positive thyroid peroxidise antibodies. MRI of the brain revealed frontal lobe and cerebellar atrophy, while neuropsychological assessment identified deficit in memory processing and executive functions. Despite appropriate correction of primary hypothyroidism with levothyroxine, the patient remained delusional with respect to age and employment although he showed some improvement in memory. Capacity for self-care remained poor; thus, he was eventually transferred to sheltered housing with rehabilitation. PMID- 22778251 TI - Postsplenectomy thromboembolic disease in congenital sideroblastic anaemia. AB - This case report describes a case of congenital sideroblastic anaemia, one of the prototype disorders of erythroid haem biosynthesis. In this instance it was not recognised until after the patient had undergone splenectomy and developed refractory thromboembolic disease. PMID- 22778252 TI - Genetic ablation of calcium-independent phospholipase A(2)gamma (iPLA(2)gamma) attenuates calcium-induced opening of the mitochondrial permeability transition pore and resultant cytochrome c release. AB - Herein, we demonstrate that calcium-independent phospholipase A(2)gamma (iPLA(2)gamma) is a critical mechanistic participant in the calcium-induced opening of the mitochondrial permeability transition pore (mPTP). Liver mitochondria from iPLA(2)gamma(-/-) mice were markedly resistant to calcium induced swelling in the presence or absence of phosphate in comparison with wild type littermates. Furthermore, the iPLA(2)gamma enantioselective inhibitor (R) (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one ((R)-BEL) was markedly more potent than (S)-BEL in inhibiting mPTP opening in mitochondria from wild-type liver in comparison with hepatic mitochondria from iPLA(2)gamma(-/-) mice. Intriguingly, low micromolar concentrations of long chain fatty acyl-CoAs and the non-hydrolyzable thioether analog of palmitoyl-CoA markedly accelerated Ca(2+)-induced mPTP opening in liver mitochondria from wild-type mice. The addition of l-carnitine enabled the metabolic channeling of acyl-CoA through carnitine palmitoyltransferases (CPT-1/2) and attenuated the palmitoyl-CoA mediated amplification of calcium-induced mPTP opening. In contrast, mitochondria from iPLA(2)gamma(-/-) mice were insensitive to fatty acyl-CoA-mediated augmentation of calcium-induced mPTP opening. Moreover, mitochondria from iPLA(2)gamma(-/-) mouse liver were resistant to Ca(2+)/t-butyl hydroperoxide induced mPTP opening in comparison with wild-type littermates. In support of these findings, cytochrome c release from iPLA(2)gamma(-/-) mitochondria was dramatically decreased in response to calcium in the presence or absence of either t-butyl hydroperoxide or phenylarsine oxide in comparison with wild-type littermates. Collectively, these results identify iPLA(2)gamma as an important mechanistic component of the mPTP, define its downstream products as potent regulators of mPTP opening, and demonstrate the integrated roles of mitochondrial bioenergetics and lipidomic flux in modulating mPTP opening promoting the activation of necrotic and necroapoptotic pathways of cell death. PMID- 22778253 TI - Modulation of histone deacetylase 6 (HDAC6) nuclear import and tubulin deacetylase activity through acetylation. AB - The reversible acetylation of histones and non-histone proteins by histone acetyltransferases and deacetylases (HDACs) plays a critical role in many cellular processes in eukaryotic cells. HDAC6 is a unique histone deacetylase with two deacetylase domains and a C-terminal zinc finger domain. HDAC6 resides mainly in the cytoplasm and regulates many important biological processes, including cell migration and degradation of misfold proteins. HDAC6 has also been shown to localize in the nucleus to regulate transcription. However, how HDAC6 shuttles between the nucleus and cytoplasm is largely unknown. In addition, it is not clear how HDAC6 enzymatic activity is modulated. Here, we show that HDAC6 can be acetylated by p300 on five clusters of lysine residues. One cluster (site B) of acetylated lysine is in the N-terminal nuclear localization signal region. These lysine residues in site B were converted to glutamine to mimic acetylated lysines. The mutations significantly reduced HDAC6 tubulin deacetylase activity and further impaired cell motility, but had no effect on histone deacetylase activity. More interestingly, these mutations retained HDAC6 in the cytoplasm by blocking the interaction with the nuclear import protein importin-alpha. The retention of HDAC6 in the cytoplasm by acetylation eventually affects histone deacetylation. Thus, we conclude that acetylation is an important post translational modification that regulates HDAC6 tubulin deacetylase activity and nuclear import. PMID- 22778254 TI - Extracellular Ca(2+) sensing in salivary ductal cells. AB - Ca(2+) is secreted from the salivary acinar cells as an ionic constituent of primary saliva. Ions such as Na(+) and Cl(-) get reabsorbed whereas primary saliva flows through the salivary ductal system. Although earlier studies have shown that salivary [Ca(2+)] decreases as it flows down the ductal tree into the oral cavity, ductal reabsorption of Ca(2+) remains enigmatic. Here we report a potential role for the G protein-coupled receptor, calcium-sensing receptor (CSR), in the regulation of Ca(2+) reabsorption by salivary gland ducts. Our data show that CSR is present in the apical region of ductal cells where it is co localized with transient receptor potential canonical 3 (TRPC3). CSR is activated in isolated salivary gland ducts as well as a ductal cell line (SMIE) by altering extracellular [Ca(2+)] or by aromatic amino acid, L-phenylalanine (L-Phe, endogenous component of saliva), as well as neomycin. CSR activation leads to Ca(2+) influx that, in polarized cells grown on a filter support, is initiated in the luminal region. We show that TRPC3 contributes to Ca(2+) entry triggered by CSR activation. Further, stimulation of CSR in SMIE cells enhances the CSR-TRPC3 association as well as surface expression of TRPC3. Together our findings suggest that CSR could serve as a Ca(2+) sensor in the luminal membrane of salivary gland ducts and regulate reabsorption of [Ca(2+)] from the saliva via TRPC3, thus contributing to maintenance of salivary [Ca(2+)]. CSR could therefore be a potentially important protective mechanism against formation of salivary gland stones (sialolithiasis) and infection (sialoadenitis). PMID- 22778255 TI - The autophagy-related protein kinase Atg1 interacts with the ubiquitin-like protein Atg8 via the Atg8 family interacting motif to facilitate autophagosome formation. AB - In autophagy, a cup-shaped membrane called the isolation membrane is formed, expanded, and sealed to complete a double membrane-bound vesicle called the autophagosome that encapsulates cellular constituents to be transported to and degraded in the lysosome/vacuole. The formation of the autophagosome requires autophagy-related (Atg) proteins. Atg8 is a ubiquitin-like protein that localizes to the isolation membrane; a subpopulation of this protein remains inside the autophagosome and is transported to the lysosome/vacuole. In the budding yeast Saccharomyces cerevisiae, Atg1 is a serine/threonine kinase that functions in the initial step of autophagosome formation and is also efficiently transported to the vacuole via autophagy. Here, we explore the mechanism and significance of this autophagic transport of Atg1. In selective types of autophagy, receptor proteins recognize degradation targets and also interact with Atg8, via the Atg8 family interacting motif (AIM), to link the targets to the isolation membrane. We find that Atg1 contains an AIM and directly interacts with Atg8. Mutations in the AIM disrupt this interaction and abolish vacuolar transport of Atg1. These results suggest that Atg1 associates with the isolation membrane by binding to Atg8, resulting in its incorporation into the autophagosome. We also show that mutations in the Atg1 AIM cause a significant defect in autophagy, without affecting the functions of Atg1 implicated in triggering autophagosome formation. We propose that in addition to its essential function in the initial stage, Atg1 also associates with the isolation membrane to promote its maturation into the autophagosome. PMID- 22778256 TI - Chimeric cellulase matrix for investigating intramolecular synergism between non hydrolytic disruptive functions of carbohydrate-binding modules and catalytic hydrolysis. AB - The conversion of renewable cellulosic biomass is of considerable interest for the production of biofuels and materials. The bottleneck in the efficient conversion is the compactness and resistance of crystalline cellulose. Carbohydrate-binding modules (CBMs), which disrupt crystalline cellulose via non hydrolytic mechanisms, are expected to overcome this bottleneck. However, the lack of convenient methods for quantitative analysis of the disruptive functions of CBMs have hindered systematic studies and molecular modifications. Here we established a practical and systematic platform for quantifying and comparing the non-hydrolytic disruptive activities of CBMs via the synergism of CBMs and a catalytic module within designed chimeric cellulase molecules. Bioinformatics and computational biology were also used to provide a deeper understanding. A convenient vector was constructed to serve as a cellulase matrix into which heterologous CBM sequences can be easily inserted. The resulting chimeric cellulases were suitable for studying disruptive functions, and their activities quantitatively reflected the disruptive functions of CBMs on crystalline cellulose. In addition, this cellulase matrix can be used to construct novel chimeric cellulases with high hydrolytic activities toward crystalline cellulose. PMID- 22778257 TI - Ca(2+)/calmodulin-dependent protein kinase IIalpha (alphaCaMKII) controls the activity of the dopamine transporter: implications for Angelman syndrome. AB - The dopamine transporter (DAT) is a crucial regulator of dopaminergic neurotransmission, controlling the length and brevity of dopaminergic signaling. DAT is also the primary target of psychostimulant drugs such as cocaine and amphetamines. Conversely, methylphenidate and amphetamine are both used clinically in the treatment of attention-deficit hyperactivity disorder and narcolepsy. The action of amphetamines, which induce transport reversal, relies primarily on the ionic composition of the intra- and extracellular milieus. Recent findings suggest that DAT interacting proteins may also play a significant role in the modulation of reverse dopamine transport. The pharmacological inhibition of the serine/threonine kinase alphaCaMKII attenuates amphetamine triggered DAT-mediated 1-methyl-4-phenylpyridinium (MPP(+)) efflux. More importantly, alphaCaMKII has also been shown to bind DAT in vitro and is therefore believed to be an important player within the DAT interactome. Herein, we show that alphaCaMKII co-immunoprecipitates with DAT in mouse striatal synaptosomes. Mice, which lack alphaCaMKII or which express a permanently self inhibited alphaCaMKII (alphaCaMKII(T305D)), exhibit significantly reduced amphetamine-triggered DAT-mediated MPP(+) efflux. Additionally, we investigated mice that mimic a neurogenetic disease known as Angelman syndrome. These mice possess reduced alphaCaMKII activity. Angelman syndrome mice demonstrated an impaired DAT efflux function, which was comparable with that of the alphaCaMKII mutant mice, indicating that DAT-mediated dopaminergic signaling is affected in Angelman syndrome. PMID- 22778258 TI - Heat shock and caloric restriction have a synergistic effect on the heat shock response in a sir2.1-dependent manner in Caenorhabditis elegans. AB - The heat shock response (HSR) is responsible for maintaining cellular and organismal health through the regulation of proteostasis. Recent data demonstrating that the mammalian HSR is regulated by SIRT1 suggest that this response may be under metabolic control. To test this hypothesis, we have determined the effect of caloric restriction in Caenorhabditis elegans on activation of the HSR and have found a synergistic effect on the induction of hsp70 gene expression. The homolog of mammalian SIRT1 in C. elegans is Sir2.1. Using a mutated C. elegans strain with a sir2.1 deletion, we show that heat shock and caloric restriction cooperate to promote increased survivability and fitness in a sir2.1-dependent manner. Finally, we show that caloric restriction increases the ability of heat shock to preserve movement in a polyglutamine toxicity neurodegenerative disease model and that this effect is dependent on sir2.1. PMID- 22778259 TI - Ligand-mimicking receptor variant discloses binding and activation mode of prolactin-releasing peptide. AB - The prolactin-releasing peptide receptor and its bioactive RF-amide peptide (PrRP20) have been investigated to explore the ligand binding mode of peptide G protein-coupled receptors (GPCRs). By receptor mutagenesis, we identified the conserved aspartate in the upper transmembrane helix 6 (Asp(6.59)) of the receptor as the first position that directly interacts with arginine 19 of the ligand (Arg(19)). Replacement of Asp(6.59) with Arg(19) of PrRP20 led to D6.59R, which turned out to be a constitutively active receptor mutant (CAM). This suggests that the mutated residue at the top of transmembrane helix 6 mimics Arg(19) by interacting with additional binding partners in the receptor. Next, we generated an initial comparative model of this CAM because no ligand docking was required, and we selected the next set of receptor mutants to find the engaged partners of the binding pocket. In an iterative process, we identified two acidic residues and two hydrophobic residues that form the peptide ligand binding pocket. As all residues are localized on top or in the upper part of the transmembrane domains, we clearly can show that the extracellular surface of the receptor is sufficient for full signal transduction for prolactin-releasing peptide, rather than a deep, membrane-embedded binding pocket. This contributes to the knowledge of the binding of peptide ligands to GPCRs and might facilitate the development of GPCR ligands, but it also provides new targeting of CAMs involved in hereditary diseases. PMID- 22778260 TI - Phosphorylation of gephyrin in hippocampal neurons by cyclin-dependent kinase CDK5 at Ser-270 is dependent on collybistin. AB - Gephyrin is a scaffold protein essential for the postsynaptic clustering of inhibitory glycine and different subtypes of GABA(A) receptors. The cellular and molecular mechanisms involved in gephyrin-mediated receptor clustering are still not well understood. Here we provide evidence that the gephyrin-binding protein collybistin is involved in regulating the phosphorylation of gephyrin. We demonstrate that the widely used monoclonal antibody mAb7a is a phospho-specific antibody that allows the cellular and biochemical analysis of gephyrin phosphorylation at Ser-270. In addition, another neighbored epitope determinant was identified at position Thr-276. Analysis of the double mutant gephyrin(T276A,S277A) revealed significant reduction in gephyrin cluster formation and altered oligomerization behavior of gephyrin. Moreover, pharmacological inhibition of cyclin-dependent kinases in hippocampal neurons reduced postsynaptic gephyrin mAb7a immunoreactivities. In vitro phosphorylation assays and phosphopeptide competition experiments revealed a phosphorylation at Ser-270 depending on enzyme activities of cyclin-dependent kinases CDK1, -2, or 5. These data indicate that collybistin and cyclin-dependent kinases are involved in regulating the phosphorylation of gephyrin at postsynaptic membrane specializations. PMID- 22778261 TI - Bacterial origin of a mitochondrial outer membrane protein translocase: new perspectives from comparative single channel electrophysiology. AB - Mitochondria are of bacterial ancestry and have to import most of their proteins from the cytosol. This process is mediated by Tom40, an essential protein that forms the protein-translocating pore in the outer mitochondrial membrane. Tom40 is conserved in virtually all eukaryotes, but its evolutionary origin is unclear because bacterial orthologues have not been identified so far. Recently, it was shown that the parasitic protozoon Trypanosoma brucei lacks a conventional Tom40 and instead employs the archaic translocase of the outer mitochondrial membrane (ATOM), a protein that shows similarities to both eukaryotic Tom40 and bacterial protein translocases of the Omp85 family. Here we present electrophysiological single channel data showing that ATOM forms a hydrophilic pore of large conductance and high open probability. Moreover, ATOM channels exhibit a preference for the passage of cationic molecules consistent with the idea that it may translocate unfolded proteins targeted by positively charged N-terminal presequences. This is further supported by the fact that the addition of a presequence peptide induces transient pore closure. An in-depth comparison of these single channel properties with those of other protein translocases reveals that ATOM closely resembles bacterial-type protein export channels rather than eukaryotic Tom40. Our results support the idea that ATOM represents an evolutionary intermediate between a bacterial Omp85-like protein export machinery and the conventional Tom40 that is found in mitochondria of other eukaryotes. PMID- 22778262 TI - The ubiquitin-specific protease 12 (USP12) is a negative regulator of notch signaling acting on notch receptor trafficking toward degradation. AB - Notch signaling is critical for development and adult tissue physiology, controlling cell fate in a context-dependent manner. Upon ligand binding, the transmembrane Notch receptor undergoes two ordered proteolytic cleavages releasing Notch intracellular domain, which regulates the transcription of Notch target genes. The strength of Notch signaling is of crucial importance and depends notably on the quantity of Notch receptor at the cell surface. Using an shRNA library screen monitoring Notch trafficking and degradation in the absence of ligand, we identified mammalian USP12 and its Drosophila melanogaster homolog as novel negative regulators of Notch signaling. USP12 silencing specifically interrupts Notch trafficking to the lysosomes and, as a consequence, leads to an increased amount of receptor at the cell surface and to a higher Notch activity. At the biochemical level, USP12 with its activator UAF1 deubiquitinate the nonactivated form of Notch in cell culture and in vitro. These results characterize a new level of conserved regulation of Notch signaling by the ubiquitin system. PMID- 22778263 TI - Calcium/calmodulin-dependent protein kinase kinase 2: roles in signaling and pathophysiology. AB - Many cellular Ca(2+)-dependent signaling cascades utilize calmodulin (CaM) as the intracellular Ca(2+) receptor. Ca(2+)/CaM binds and activates a plethora of enzymes, including CaM kinases (CaMKs). CaMKK2 is one of the most versatile of the CaMKs and will phosphorylate and activate CaMKI, CaMKIV, and AMP-activated protein kinase. Cell expression of CaMKK2 is limited, yet CaMKK2 is involved in regulating many important physiological and pathophysiological processes, including energy balance, adiposity, glucose homeostasis, hematopoiesis, inflammation, and cancer. Here, we explore known functions of CaMKK2 and discuss its potential as a target for therapeutic intervention. PMID- 22778264 TI - Osteoblast-like differentiation of cultured human coronary artery smooth muscle cells by bone morphogenetic protein endothelial cell precursor-derived regulator (BMPER). AB - Differentiation of vascular smooth muscle cells (SMCs) into osteoblast-like cells is considered to be a mechanism of vascular calcification. However, regulators of osteoblast-like differentiation of vascular SMCs are not fully elucidated. Here, we investigated the expression of bone morphogenetic protein (BMP)-binding endothelial cell precursor-derived regulator (BMPER), a vertebrate homologue of Drosophila crossveinless-2, in vascular SMCs and the role and mode of action of BMPER in osteoblast-like differentiation of human coronary artery SMCs (HCASMCs). BMPER was expressed in cultured human vascular SMCs, including HCASMCs. Silencing of endogenous BMPER expression by an RNA interference technique inhibited osteoblast-like differentiation of HCASMCs, as evaluated by up-regulation of osteoblast markers such as alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2), by down-regulation of a SMC marker alpha-smooth muscle actin (alphaSMA), and by mineralization. Treatment with recombinant BMPER enhanced, whereas BMP-2 reduced osteoblast-like differentiation. BMPER antagonized BMP-2-induced phosphorylation of Smad 1/5/8, suggesting that the effect of BMPER was mediated by antagonizing the action of BMP. BMPER increased IkappaBalpha phosphorylation and NF-kappaB activity and specific NF-kappaB decoy oligonucleotides deteriorated osteoblast-like differentiation of HCASMCs by BMPER. In human coronary artery with atherosclerotic plaque containing calcification, the BMPER-positive signals were observed in the neointimal and medial SMCs in the vicinity of the plaque. These findings indicate that BMPER is a novel regulator of the osteoblast-like differentiation of HCASMCs. PMID- 22778265 TI - Toad heart utilizes exclusively slow skeletal muscle troponin T: an evolutionary adaptation with potential functional benefits. AB - The three isoforms of vertebrate troponin T (TnT) are normally expressed in a muscle type-specific manner. Here we report an exception that the cardiac muscle of toad (Bufo) expresses exclusively slow skeletal muscle TnT (ssTnT) together with cardiac forms of troponin I and myosin as determined using immunoblotting, cDNA cloning, and/or LC-MS/MS. Using RT-PCR and 3'- and 5'-rapid amplification of cDNA ends on toad cardiac mRNA, we cloned full-length cDNAs encoding two alternatively spliced variants of ssTnT. Expression of the cloned cDNAs in Escherichia coli confirmed that the toad cardiac muscle expresses solely ssTnT, predominantly the low molecular weight variant with the exon 5-encoded NH(2) terminal segment spliced out. Functional studies were performed in ex vivo working toad hearts and compared with the frog (Rana) hearts. The results showed that toad hearts had higher contractile and relaxation velocities and were able to work against a significantly higher afterload than that of frog hearts. Therefore, the unique evolutionary adaptation of utilizing exclusively ssTnT in toad cardiac muscle corresponded to a fitness value from improving systolic function of the heart. The data demonstrated a physiological importance of the functional diversity of TnT isoforms. The structure-function relationship of TnT may be explored for the development of new treatment of heart failure. PMID- 22778266 TI - A novel mechanism involving four-and-a-half LIM domain protein-1 and extracellular signal-regulated kinase-2 regulates titin phosphorylation and mechanics. AB - Understanding mechanisms underlying titin regulation in cardiac muscle function is of critical importance given recent compelling evidence that highlight titin mutations as major determinants of human cardiomyopathy. We previously identified a cardiac biomechanical stress-regulated complex at the cardiac-specific N2B region of titin that includes four-and-a-half LIM domain protein-1 (Fhl1) and components of the mitogen-activated protein signaling cascade, which impacted muscle compliance in Fhl1 knock-out cardiac muscle. However, direct regulation of these molecular components in mediating titin N2B function remained unresolved. Here we identify Fhl1 as a novel negative regulator of titin N2B levels and phosphorylation-mediated mechanics. We specifically identify titin N2B as a novel substrate of extracellular signal regulated-kinase-2 (Erk2) and demonstrate that Fhl1 directly interferes with Erk2-mediated titin-N2B phosphorylation. We highlight the critical region in titin-N2B that interacts with Fhl1 and residues that are dependent on Erk2-mediated phosphorylation in situ. We also propose a potential mechanism for a known titin-N2B cardiomyopathy-causing mutation that involves this regulatory complex. These studies shed light on a novel mechanism regulating titin-N2B mechano-signaling as well as suggest that dysfunction of these pathways could be important in cardiac disease states affecting muscle compliance. PMID- 22778267 TI - Zyxin is a transforming growth factor-beta (TGF-beta)/Smad3 target gene that regulates lung cancer cell motility via integrin alpha5beta1. AB - Although TGF-beta acts as a tumor suppressor in normal tissues and in early carcinogenesis, these tumor suppressor effects are lost in advanced malignancies. Single cell migration and epithelial-mesenchymal transition (EMT), both of which are regulated by TGF-beta, are critical steps in mediating cancer progression. Here, we sought to identify novel direct targets of TGF-beta signaling in lung cancer cells and have indentified the zyxin gene as a target of Smad3-mediated TGF-beta1 signaling. Zyxin concentrates at focal adhesions and along the actin cytoskeleton; as such, we hypothesized that cytoskeletal organization, motility, and EMT in response to TGF-beta1 might be regulated by zyxin expression. We show that TGF-beta1 treatment of lung cancer cells caused rapid phospho-Smad3 dependent expression of zyxin. Zyxin expression was critical for the formation and integrity of cell adherens junctions. Silencing of zyxin decreased expression of the focal adhesion protein vasodilator-activated phospho-protein (VASP), although the formation and morphology of focal adhesions remained unchanged. Zyxin-depleted cells displayed significantly increased integrin alpha5beta1 levels, accompanied by enhanced adhesion to fibronectin and acquisition of a mesenchymal phenotype in response to TGF-beta1. Zyxin silencing led to elevated integrin alpha5beta1-dependent single cell motility. Importantly, these features are mirrored in the K-ras-driven mouse model of lung cancer. Here, lung tumors revealed decreased levels of both zyxin and phospho-Smad3 when compared with normal tissues. Our data thus demonstrate that zyxin is a novel functional target and effector of TGF-beta signaling in lung cancer. By regulating cell-cell junctions, integrin alpha5beta1 expression, and cell-extracellular matrix adhesion, zyxin may regulate cancer cell motility and EMT during lung cancer development and progression. PMID- 22778268 TI - Use of quantitative membrane proteomics identifies a novel role of mitochondria in healing injured muscles. AB - Skeletal muscles are proficient at healing from a variety of injuries. Healing occurs in two phases, early and late phase. Early phase involves healing the injured sarcolemma and restricting the spread of damage to the injured myofiber. Late phase of healing occurs a few days postinjury and involves interaction of injured myofibers with regenerative and inflammatory cells. Of the two phases, cellular and molecular processes involved in the early phase of healing are poorly understood. We have implemented an improved sarcolemmal proteomics approach together with in vivo labeling of proteins with modified amino acids in mice to study acute changes in the sarcolemmal proteome in early phase of myofiber injury. We find that a notable early phase response to muscle injury is an increased association of mitochondria with the injured sarcolemma. Real-time imaging of live myofibers during injury demonstrated that the increased association of mitochondria with the injured sarcolemma involves translocation of mitochondria to the site of injury, a response that is lacking in cultured myoblasts. Inhibiting mitochondrial function at the time of injury inhibited healing of the injured myofibers. This identifies a novel role of mitochondria in the early phase of healing injured myofibers. PMID- 22778269 TI - Thioredoxin reductase linked to cytoskeleton by focal adhesion kinase reverses actin S-nitrosylation and restores neutrophil beta(2) integrin function. AB - The investigation goal was to identify mechanisms for reversal of actin S nitrosylation in neutrophils after exposure to high oxygen partial pressures. Prior work has shown that hyperoxia causes S-nitrosylated actin (SNO-actin) formation, which mediates beta(2) integrin dysfunction, and these changes can be reversed by formylmethionylleucylphenylalanine or 8-bromo-cyclic GMP. Herein we show that thioredoxin reductase (TrxR) is responsible for actin denitrosylation. Approximately 80% of cellular TrxR is localized to the cytosol, divided between the G-actin and short filamentous actin (sF-actin) fractions based on Triton solubility of cell lysates. TrxR linkage to sF-actin requires focal adhesion kinase (FAK) based on immunoprecipitation studies. S-Nitrosylation accelerates actin filament turnover (by mechanisms described previously (Thom, S. R., Bhopale, V. M., Yang, M., Bogush, M., Huang, S., and Milovanova, T. (2011) Neutrophil beta(2) integrin inhibition by enhanced interactions of vasodilator stimulated phosphoprotein with S-nitrosylated actin. J. Biol. Chem. 286, 32854 32865), which causes FAK to disassociate from sF-actin. TrxR subsequently dissociates from FAK, and the physical separation from actin impedes denitrosylation. If SNO-actin is photochemically reduced with UV light or if actin filament turnover is impeded by incubations with cytochalasin D, latrunculin B, 8-bromo-cGMP, or formylmethionylleucylphenylalanine, FAK and TrxR reassociate with sF-actin and cause SNO-actin removal. FAK-TrxR association can also be demonstrated using isolated enzymes in ex vivo preparations. Uniquely, the FAK kinase domain is the site of TrxR linkage. We conclude that through its scaffold function, FAK influences TrxR activity and actin S-nitrosylation. PMID- 22778270 TI - The A-kinase anchoring protein Yotiao facilitates complex formation between adenylyl cyclase type 9 and the IKs potassium channel in heart. AB - The scaffolding protein Yotiao is a member of a large family of protein A-kinase anchoring proteins with important roles in the organization of spatial and temporal signaling. In heart, Yotiao directly associates with the slow outward potassium ion current (I(Ks)) and recruits both PKA and PP1 to regulate I(Ks) phosphorylation and gating. Human mutations that disrupt I(Ks)-Yotiao interaction result in reduced PKA-dependent phosphorylation of the I(Ks) subunit KCNQ1 and inhibition of sympathetic stimulation of I(Ks), which can give rise to long-QT syndrome. We have previously identified a subset of adenylyl cyclase (AC) isoforms that interact with Yotiao, including AC1-3 and AC9, but surprisingly, this group did not include the major cardiac isoforms AC5 and AC6. We now show that either AC2 or AC9 can associate with KCNQ1 in a complex mediated by Yotiao. In transgenic mouse heart expressing KCNQ1-KCNE1, AC activity was specifically associated with the I(Ks)-Yotiao complex and could be disrupted by addition of the AC9 N terminus. A survey of all AC isoforms by RT-PCR indicated expression of AC4-6 and AC9 in adult mouse cardiac myocytes. Of these, the only Yotiao interacting isoform was AC9. Furthermore, the endogenous I(Ks)-Yotiao complex from guinea pig also contained AC9. Finally, AC9 association with the KCNQ1 Yotiao complex sensitized PKA phosphorylation of KCNQ1 to beta-adrenergic stimulation. Thus, in heart, Yotiao brings together PKA, PP1, PDE4D3, AC9, and the I(Ks) channel to achieve localized temporal regulation of beta-adrenergic stimulation. PMID- 22778271 TI - Ankyrin-B protein in heart failure: identification of a new component of metazoan cardioprotection. AB - Ankyrins (ankyrin-R, -B, and -G) are adapter proteins linked with defects in metazoan physiology. Ankyrin-B (encoded by ANK2) loss-of-function mutations are directly associated with human cardiovascular phenotypes including sinus node disease, atrial fibrillation, ventricular tachycardia, and sudden cardiac death. Despite the link between ankyrin-B dysfunction and monogenic disease, there are no data linking ankyrin-B regulation with common forms of human heart failure. Here, we report that ankyrin-B levels are altered in both ischemic and non ischemic human heart failure. Mechanistically, we demonstrate that cardiac ankyrin-B levels are tightly regulated downstream of reactive oxygen species, intracellular calcium, and the calcium-dependent protease calpain, all hallmarks of human myocardial injury and heart failure. Surprisingly, beta(II)-spectrin, previously thought to mediate ankyrin-dependent modulation in the nervous system and heart, is not coordinately regulated with ankyrin-B or its downstream partners. Finally, our data implicate ankyrin-B expression as required for vertebrate myocardial protection as hearts deficient in ankyrin-B show increased cardiac damage and impaired function relative to wild-type mouse hearts following ischemia reperfusion. In summary, our findings provide the data of ankyrin-B regulation in human heart failure, provide insight into candidate pathways for ankyrin-B regulation in acquired human cardiovascular disease, and surprisingly, implicate ankyrin-B as a molecular component for cardioprotection following ischemia. PMID- 22778272 TI - Biochemical and structural characterization of the complex agarolytic enzyme system from the marine bacterium Zobellia galactanivorans. AB - Zobellia galactanivorans is an emerging model bacterium for the bioconversion of algal biomass. Notably, this marine Bacteroidetes possesses a complex agarolytic system comprising four beta-agarases and five beta-porphyranases, all belonging to the glycoside hydrolase family 16. Although beta-agarases are specific for the neutral agarobiose moieties, the recently discovered beta-porphyranases degrade the sulfated polymers found in various quantities in natural agars. Here, we report the biochemical and structural comparison of five beta-porphyranases and beta-agarases from Z. galactanivorans. The respective degradation patterns of two beta-porphyranases and three beta-agarases are analyzed by their action on defined hybrid oligosaccharides. In light of the high resolution crystal structures, the biochemical results allowed a detailed mapping of substrate specificities along the active site groove of the enzymes. Although PorA displays a strict requirement for C6-sulfate in the -2- and +1-binding subsites, PorB tolerates the presence of 3-6-anhydro-l-galactose in subsite -2. Both enzymes do not accept methylation of the galactose unit in the -1 subsite. The beta-agarase AgaD requires at least four consecutive agarose units (DP8) and is highly intolerant to modifications, whereas for AgaB oligosaccharides containing C6 sulfate groups at the -4, +1, and +3 positions are still degraded. Together with a transcriptional analysis of the expression of these enzymes, the structural and biochemical results allow proposition of a model scheme for the agarolytic system of Z. galactanivorans. PMID- 22778274 TI - Jiri Lukas: Visualizing genome integrity maintenance. Interview by Caitlin Sedwick. PMID- 22778273 TI - Characterization and immunotherapeutic implications for a novel antibody targeting interleukin (IL)-13 receptor alpha2. AB - The high affinity interleukin-13 receptor alpha2 (IL13Ralpha2) is selectively expressed at a high frequency by glioblastoma multiforme (GBM) as well as several other tumor types. One approach for targeting this tumor-specific receptor utilizes the cognate ligand, IL-13, conjugated to cytotoxic molecules. However, this approach lacks specificity because the lower affinity receptor for IL-13, IL13Ralpha1, is widely expressed by normal tissues. Here, we aimed to develop and characterize a novel monoclonal antibody (mAb) specific to IL13Ralpha2 for the therapeutic purpose of targeting IL13Ralpha2-expressing tumors. Hybridoma cell lines were generated and compared for binding affinities to recombinant human IL13Ralpha2 (rhIL13Ralpha2). Clone 47 demonstrated binding to the native conformation of IL13Ralpha2 and was therefore chosen for further studies. Clone 47 bound specifically and with high affinity (K(D) = 1.39 * 10(-9) M) to rhIL13Ralpha2 but not to rhIL13Ralpha1 or murine IL13Ralpha2. Furthermore, clone 47 specifically recognized wild-type IL13Ralpha2 expressed on the surface of CHO and HEK cells as well as several glioma cell lines. Competitive binding assays revealed that clone 47 also significantly inhibited the interaction between human soluble IL-13 and IL13Ralpha2 receptor. Moreover, we found that N-linked glycosylation of IL13Ralpha2 contributes in part to the interaction of the antibody to IL13Ralpha2. In vivo, the IL13Ralpha2 mAb improved the survival of nude mice intracranially implanted with a human U251 glioma xenograft. Collectively, these data warrant further investigation of this novel IL13Ralpha2 mAb with an emphasis on translational implications for therapeutic use. PMID- 22778275 TI - Presenilins: a novel link between intracellular calcium signaling and lysosomal function? AB - Mutations in presenilins (PS), transmembrane proteins encoding the catalytic subunit of gamma-secretase, result in familial Alzheimer's disease (FAD). Several studies have identified lysosomal defects in cells lacking PS or expressing FAD associated PS mutations, which have been previously attributed to a function for PS in lysosomal acidification. Now, in this issue, Coen et al. (2012. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201201076) provide a series of results that challenge this idea and propose instead that presenilins play a role in calcium mediated lysosomal fusion. PMID- 22778277 TI - Control of vertebrate intraflagellar transport by the planar cell polarity effector Fuz. AB - Cilia play key roles in development and homeostasis, and defects in cilia structure or function lead to an array of human diseases. Ciliogenesis is accomplished by the intraflagellar transport (IFT) system, a set of proteins governing bidirectional transport of cargoes within ciliary axonemes. In this paper, we present a novel platform for in vivo analysis of vertebrate IFT dynamics. Using this platform, we show that the planar cell polarity (PCP) effector Fuz was required for normal IFT dynamics in vertebrate cilia, the first evidence directly linking PCP to the core machinery of ciliogenesis. Further, we show that Fuz played a specific role in trafficking of retrograde, but not anterograde, IFT proteins. These data place Fuz in the small group of known IFT effectors outside the core machinery and, additionally, identify Fuz as a novel cytoplasmic effector that differentiates between the retrograde and anterograde IFT complexes. PMID- 22778276 TI - The cell biology of disease: Acute promyelocytic leukemia, arsenic, and PML bodies. AB - Acute promyelocytic leukemia (APL) is driven by a chromosomal translocation whose product, the PML/retinoic acid (RA) receptor alpha (RARA) fusion protein, affects both nuclear receptor signaling and PML body assembly. Dissection of APL pathogenesis has led to the rediscovery of PML bodies and revealed their role in cell senescence, disease pathogenesis, and responsiveness to treatment. APL is remarkable because of the fortuitous identification of two clinically effective therapies, RA and arsenic, both of which degrade PML/RARA oncoprotein and, together, cure APL. Analysis of arsenic-induced PML or PML/RARA degradation has implicated oxidative stress in the biogenesis of nuclear bodies and SUMO in their degradation. PMID- 22778278 TI - Myo1c facilitates G-actin transport to the leading edge of migrating endothelial cells. AB - Addition of actin monomer (G-actin) to growing actin filaments (F-actin) at the leading edge generates force for cell locomotion. The polymerization reaction and its regulation have been studied in depth. However, the mechanism responsible for transport of G-actin substrate to the cell front is largely unknown; random diffusion, facilitated transport via myosin II contraction, local synthesis as a result of messenger ribonucleic acid localization, or F-actin turnover all might contribute. By tracking a photoactivatable, nonpolymerizable actin mutant, we show vectorial transport of G-actin in live migrating endothelial cells (ECs). Mass spectrometric analysis identified Myo1c, an unconventional F-actin-binding motor protein, as a major G-actin-interacting protein. The cargo-binding tail domain of Myo1c interacted with G-actin, and the motor domain was required for the transport. Local microinjection of Myo1c promoted G-actin accumulation and plasma membrane ruffling, and Myo1c knockdown confirmed its contribution to G actin delivery to the leading edge and for cell motility. In addition, there is no obvious requirement for myosin II contractile-based transport of G-actin in ECs. Thus, Myo1c-facilitated G-actin transport might be a critical node for control of cell polarity and motility. PMID- 22778280 TI - A decade after the women's health initiative--the experts do agree. PMID- 22778279 TI - Evi5 promotes collective cell migration through its Rab-GAP activity. AB - Membrane trafficking has well-defined roles during cell migration. However, its regulation is poorly characterized. In this paper, we describe the first screen for putative Rab-GTPase-activating proteins (GAPs) during collective cell migration of Drosophila melanogaster border cells (BCs), identify the uncharacterized Drosophila protein Evi5 as an essential membrane trafficking regulator, and describe the molecular mechanism by which Evi5 regulates BC migration. Evi5 requires its Rab-GAP activity to fulfill its functions during migration and acts as a GAP protein for Rab11. Both loss and gain of Evi5 function blocked BC migration by disrupting the Rab11-dependent polarization of active guidance receptors. Altogether, our findings deepen our understanding of the molecular machinery regulating endocytosis and subsequently cell signaling during migration. PMID- 22778281 TI - Bilateral psoas abscesses and vertebral osteomyelitis in a patient with sickle cell disease. AB - The authors present a case of a patient with sickle-beta thalassaemia (Sbeta(0) Thal) who had bilateral psoas abscesses on a background of splenectomy in early childhood. The patient also turned out to have vertebral osteomyelitis and hydronephrosis on the side of the larger abscess. The only organism recovered from the patient was a Bacteroides species. The patient was managed with percutaneous drainage and intravenous antibiotics and made a full recovery. PMID- 22778282 TI - Solitary plexiform neurofibroma, a pitfall in diagnosis of lipoma. AB - Plexiform neurofibromatosis is almost invariably associated with neurofibromatosis type I. A case of an isolated back plexiform neurofibroma, initially thought to be a lipoma, is presented, with emphasis on the importance of eliciting family history in reaching a diagnosis of neurofibromatosis. Currently, surgical resection is still the treatment of choice though a management plan is not well defined. Patients need appropriate regular follow-up to detect malignancy or early recurrence. PMID- 22778283 TI - A rare complication with a single dose of alendronate. AB - The authors present a case of an 84-year-old patient who presented to the emergency department with sudden onset abdominal pain radiating to the neck. The patient's medication included warfarin, and alendronate, which was started by the general practitioner 2 days prior to presentation. Initial systemic examination and investigations, including chest x-ray, were unremarkable. Within 24 h of presentation the patient developed bilateral pneumonia with effusions. Due to continued clinical deterioration over the next 48 h, a CT thorax was performed that showed evidence of large oesophageal perforation with mediastinitis and gas in the mediastinum. The patient was treated with an expandable metal stent, bilateral chest drains, broad spectrum antibiotics, antifungals and total parenteral nutrition. Over a period of 8 weeks the patient made an excellent recovery. This rare case illustrates the importance of vigilance for the life threatening complication of oesophageal perforation with alendronate treatment. PMID- 22778284 TI - Management of tibial non-union with tricalcium phosphate and BMP 7. AB - We present the case of a 30-year-old woman who was referred with an established tibial non-union with a bone defect following a spiral fracture of the tibia. Initial attempts at union with intramedullary fixation and then autograft were unsuccessful. We achieved union by debriding the fibrous tissue and packing the defect with Bone Morphogenetic Protein 7 (Osigraft, Stryker, UK) and a tricalcium phosphate bone void filler (Calstrux, Stryker, UK). We did not use any additional surgical fixation and the patient was supported in an aircast boot. PMID- 22778285 TI - Breast 'rupture' due to a phyllodes tumour. PMID- 22778286 TI - Incidental finding of an anterior sub-hepatic appendix during laparoscopic cholecystectomy. PMID- 22778287 TI - Atypical presentation of a giant spinal schwannoma. PMID- 22778288 TI - The serotonin syndrome as a result of mephedrone toxicity. AB - A 22-year-old male presented to an emergency department by ambulance. His clinical picture included tachycardia, diaphoresis, hypertonia, hyper-reflexia and clonus. The patient became hyperthermic and deteriorated over the next hour. The principal substance ingested was mephedrone and appropriate treatment for the serotonin syndrome resulted in a sustained recovery over 15 h. PMID- 22778289 TI - An unusual cause of neonatal respiratory distress. PMID- 22778290 TI - An ocular presentation of familial tumoral calcinosis. AB - This case report presents the ophthalmic features and complications of a 56-year old Caucasian woman with familial tumoral calcinosis. She presented to our ophthalmology clinic with a 3-month history of blurring of her vision. She had been diagnosed 14 years earlier with familial tumoral calcinosis. Ophthalmological examination revealed calcific depositions on the eyelid margins, perilimbal calcific deposits and angioid streaks. An optical coherence tomography scan of the left eye revealed a choroidal neovascular membrane. Deterioration in vision occurred secondary to subretinal haemorrhage, resulting from the angioid streak. The patient was treated with a series of three intravitreal ranibizumab injections to her left eye, which led to an improvement in her visual acuity (VA). The patient is being closely followed up with monthly appointments, and to date, after 6 months of follow-up, there has been no further deterioration in her VA or reactivation of the choroidal neovascular membrane. PMID- 22778291 TI - A young mountaineer surviving sudden cardiac arrest at high altitude. AB - A young mountaineer suffered from sudden cardiac arrest at high altitude. Cardiopulmonary resuscitation was initiated immediately. After 30 min a rescue team arrived and successfully defibrillated ventricular fibrillation upon which spontaneous circulation returned. The subsequent ECG was suggestive of extensive anterior myocardial infarction. Therefore, the patient was thrombolysed and transferred for primary percutaneous coronary intervention. Echocardiography revealed severely reduced left ventricular function with antero-septo-apical akinesia. However, angiography showed unobstructed coronary arteries. The patient fully recovered and left ventricular function normalised within 2 weeks. It may be speculated that exposure to high altitude resulted in acute coronary thrombosis which dissolved by rapid thrombolysis. PMID- 22778292 TI - Minimal access is not maximal safety: pelviureteric necrosis following percutaneous chemical lumbar sympathectomy. AB - Lumbar sympathectomy remains popular in the treatment of a variety of painful and circulatory conditions of the lower extremities. Although percutaneous chemical lumbar sympathectomy (PCLS) under radiographic guidance is minimally invasive and has decreased the need for open surgical sympathectomy, inadvertent damage to neighbouring structures is a matter for concern. We report the case of a 38-year old man with thromboangiitis obliterans who had PCLS under radiographic guidance for relief of ischaemic rest pain that was complicated by necrotic disruption of the left pelviureteric region. The kidney was salvaged with an ureterocalycostomy and he remains well 4 years later. Such complications point to imprecise and unpredictable spread of the injected chemical too far beyond the needle tip. It is possible that such complications are often under reported and, therefore, not taken into consideration during informed consent. Precise neurolysis with laser and radiofrequency may be a safer alternative. PMID- 22778293 TI - An atypical pleural effusion. PMID- 22778294 TI - Porphyria or not porphyria - that is the question... PMID- 22778295 TI - Aggressive Dupuytren's diathesis in a young woman. AB - Dupuytren's disease is a palmar fascia pathology characterised by flexion contracture of the involved fingers in late stages. It has been described a higher prevalence in northern populations, especially in men in the fifth or sixth decade of life.1 Alcohol consumption, liver disease, diabetes mellitus, epilepsy and some of its treatments, tobacco smokers or hand workers are only a example of the different aetiologies proposed. There are a group of patients presenting with more aggressive clinical manifestation named Dupuytren's diathesis. This subtype could frequently present a positive family history, ectopic fibromatosis and bilateral hand affectation. The authors present a 24 year-old woman referred to the Plastic Surgery Department because severe fingers contracture with an associated aggressive plantar fibromatosis. She referred familial history in her first degree relatives (mother and three of seven brothers and sisters). The first clinical manifestations in her hand began when she was 7 years old. PMID- 22778296 TI - Caffeine intake during pregnancy and risk of problem behavior in 5- to 6-year-old children. AB - BACKGROUND AND OBJECTIVE: Human studies that have investigated the association between caffeine intake during pregnancy and offspring's behavioral outcomes are scant and inconclusive. We prospectively investigated the association between maternal caffeine intake during pregnancy and children's problem behavior at age 5 to 6 years. Mediation by fetal growth restriction and gestational age as well as effect modification by the child's gender and maternal smoking was tested. METHODS: In a community based multiethnic birth cohort, dietary caffeine intake (coffee, caffeinated tea, and cola) was measured (maternal self-report, n = 8202) around the 16th week of gestation. At age 5, children's overall problem behavior, emotional problems, conduct problems, hyperactivity/inattention problems, peer relationship problems, and prosocial behavior were rated by both mother and teacher (n = 3439) with the Strengths and Difficulties Questionnaire. Analyses were adjusted for maternal age, ethnicity, cohabitant status, education, smoking and alcohol consumption during pregnancy, child's gender, family size, and prenatal maternal anxiety. RESULTS: Caffeine intake was not associated with a higher risk for behavior problems or with suboptimal prosocial behavior. No evidence was found for mediation by fetal growth restriction or gestational age, nor for effect modification by the child's gender. CONCLUSIONS: Results did not provide evidence for developmental programming influences of intrauterine exposure to caffeine on offspring's problem behavior at age 5. Present results give no indication to advise pregnant women to reduce their caffeine intake to prevent behavior problems in their children. PMID- 22778297 TI - Vaccine-type human papillomavirus and evidence of herd protection after vaccine introduction. AB - OBJECTIVES: The aims of this study were to compare prevalence rates of human papillomavirus (HPV) in young women before and after HPV vaccine introduction to determine the following: (1) whether vaccine-type HPV infection decreased, (2) whether there was evidence of herd protection, and (3) whether there was evidence for type-replacement (increased prevalence of nonvaccine-type HPV). METHODS: Young women 13 to 26 years of age who had had sexual contact were recruited from 2 primary care clinics in 2006-2007 for a prevaccination surveillance study (N = 368, none were vaccinated) and 2009-2010 for a postvaccination surveillance study (N = 409, 59% were vaccinated). Participants completed a questionnaire and were tested for cervicovaginal HPV DNA. HPV prevalence rates were compared in the pre- versus postsurveillance studies by using chi(2) tests. Propensity score weighting was used to balance differences in covariates between the 2 surveillance studies. RESULTS: The mean age was ~19 years for both groups of participants and most were African American and non-Hispanic. After propensity score weighting, the prevalence rate for vaccine-type HPV decreased substantially (31.7%-13.4%, P < .0001). The decrease in vaccine-type HPV not only occurred among vaccinated (31.8%-9.9%, P < .0001) but also among unvaccinated (30.2%-15.4%, P < .0001) postsurveillance study participants. Nonvaccine-type HPV increased (60.7%-75.9%, P < .0001) for vaccinated postsurveillance study participants. CONCLUSIONS: Four years after licensing of the quadrivalent HPV vaccine, there was a substantial decrease in vaccine-type HPV prevalence and evidence of herd protection in this community. The increase in nonvaccine-type HPV in vaccinated participants should be interpreted with caution but warrants further study. PMID- 22778298 TI - Adolescent dating violence: a national assessment of school counselors' perceptions and practices. AB - BACKGROUND AND OBJECTIVES: Adolescent dating violence (ADV) is a significant public health problem that, according to various estimates, affects 9% to 34% of adolescents in the United States. Schools can play an important role in preventing ADV. However, little is known about school personnel's practices and perceptions regarding ADV. This study assessed high school counselors' knowledge, training, perceptions, and practices on dealing with ADV incidents. METHODS: A national random sample (n = 550) of high school counselors who were members of the American School Counselors Association were sent a valid and reliable questionnaire on ADV. A 3-wave mailing procedure was used to increase the response rate, which was 58%. Statistically significant differences (P < .05) were calculated by using t tests, chi(2) tests, analysis of variance, and logistic regression. RESULTS: A majority of the school counselors reported that they did not have a protocol in their schools to respond to an incident of ADV (81.3%). Additionally, the majority (90%) of counselors reported that in the past 2 years, training to assist survivors of teen dating abuse has not been provided to personnel in their schools, their school did not conduct periodic student surveys that include questions on teen dating abuse behaviors (83%), and their school did not have a committee that meets periodically to address health and safety issues that include teen dating abuse (76%). CONCLUSIONS: The results of this study indicate that schools do not find ADV a high-priority issue to be addressed in their student populations. PMID- 22778299 TI - Family experiences and pediatric health services use associated with family centered rounds. AB - BACKGROUND: Family-centered rounds (FCR) are defined as interdisciplinary bedside teaching rounds with active family participation. The objective of this study was to examine the association of FCR with family experiences and health services use. METHODS: Prospective study comparing families with a child admitted to general pediatric inpatient services with and without FCR. The presence of FCR elements was assessed before study enrollment. Study data were obtained by an in person interview, a follow-up phone interview <1 week after discharge, and medical record review. Family outcomes were informed by Consumer Assessment of Healthcare Providers and Systems measures. Health service use outcomes included hour of discharge, number of medications, and overall charges. Primary analyses included chi(2) and multivariate regression. Secondary analyses by using propensity score matching were performed to account for differences on observed variables. RESULTS: A total of 140 of 203 eligible families were enrolled; 97 completed follow-up surveys (49 on FCR team). Compared with non-FCR, FCR families were more likely to report consistent medical information (P < .001), the option of discussing care plan (P < .001), doctors listening carefully (P < .01), and doctors showing respect (P < .001). No differences were found in number of medications (mean 2.4 vs 2.9, P = .26) or discharge time (mean 3:06 pm versus 2:43 pm, P = .39). No difference was found for hospital charges after adjusting for length of stay outliers. CONCLUSIONS: FCR are associated with higher parent satisfaction, consistent medical information, and care plan discussion, with no additional burden to health service use. Additional studies should assess FCR under different settings of care. PMID- 22778300 TI - Prevalence of abusive injuries in siblings and household contacts of physically abused children. AB - OBJECTIVE: Siblings and other children who share a home with a physically abused child are thought to be at high risk for abuse, but rates of injury in these contact children are unknown and screening of contacts is highly variable. Our objective was to determine the prevalence of abusive injuries identified by a common screening protocol among contacts of physically abused children. METHODS: This is an observational, multicenter cross-sectional study of children evaluated for physical abuse, and their contacts, by 20 US child abuse teams who used a common screening protocol for the contacts of physically abused children with serious injuries. Contacts underwent physical examination if they were <5 years old, physical examination and skeletal survey (SS) if they were <24 months old, and physical examination, SS, and neuroimaging if they were <6 months old. RESULTS: Protocol-indicated SS identified at least 1 abusive fracture in 16 of 134 contacts (11.9%, 95% confidence interval [CI] 7.5-18.5) <24 months of age. None of these fractures had associated findings on physical examination. No injuries were identified by neuroimaging in 19 of 25 eligible contacts (0.0%, 95% CI 0.0-13.7). Twins were at substantially increased risk of fracture relative to nontwin contacts (odds ratio 20.1, 95% CI 5.8-69.9). CONCLUSIONS: SS should be obtained in the contacts of injured, abused children for contacts who are <24 months old, regardless of physical examination findings. Twins are at higher risk of abusive fractures relative to nontwin contacts. PMID- 22778301 TI - The differential impact of delivery hospital on the outcomes of premature infants. AB - BACKGROUND: Because greater percentages of women deliver at hospitals without high-level NICUs, there is little information on the effect of delivery hospital on the outcomes of premature infants in the past 2 decades, or how these effects differ across states with different perinatal regionalization systems. METHODS: A retrospective population-based cohort study was constructed of all hospital-based deliveries in Pennsylvania and California between 1995 and 2005 and Missouri between 1995 and 2003 with a gestational age between 23 and 37 weeks (N = 1328132). The effect of delivery at a high-level NICU on in-hospital death and 5 complications of premature birth was calculated by using an instrumental variables approach to control for measured and unmeasured differences between hospitals. RESULTS: Infants who were delivered at a high-level NICU had significantly fewer in-hospital deaths in Pennsylvania (7.8 fewer deaths/1000 deliveries, 95% confidence interval [CI] 4.1-11.5), California (2.7 fewer deaths/1000 deliveries, 95% CI 0.9-4.5), and Missouri (12.6 fewer deaths/1000 deliveries, 95% CI 2.6-22.6). Deliveries at high-level NICUs had similar rates of most complications, with the exception of lower bronchopulmonary dysplasia rates at Missouri high-level NICUs (9.5 fewer cases/1000 deliveries, 95% CI 0.7-18.4) and higher infection rates at high-level NICUs in Pennsylvania and California. The association between delivery hospital, in-hospital mortality, and complications differed across the 3 states. CONCLUSIONS: There is benefit to neonatal outcomes when high-risk infants are delivered at high-level NICUs that is larger than previously reported, although the effects differ between states, which may be attributable to different methods of regionalization. PMID- 22778302 TI - Influence of smoking cues in movies on children's beliefs about smoking. AB - OBJECTIVE: Experimental research has revealed that short exposure to movie smoking affects beliefs about smoking in adolescents. In this study, we tested that association in children. METHODS: In 2 experiments, participants were exposed to either a cartoon or family-oriented movie and randomly assigned to 20 minute segments with or without smoking characters. Data collection took place at elementary schools. A total of 101 children (8-10 years; 47.5% boys) were exposed to a cartoon, and in a second experiment, 105 children (8-11 years; 56.2% boys) were exposed to a family-oriented movie. Beliefs about smoking (assessed by questionnaire) and implicit associations toward smoking (single target implicit association task) were assessed after watching the movie. RESULTS: The majority of both samples of children viewed smoking unfavorably. Exposure to movie smoking had no effect on implicit associations toward smoking when experiments were analyzed separately or if the results were combined. For smoking beliefs, effects were again small and only statistically significant for social norms regarding smoking. CONCLUSIONS: Short-term exposure to smoking in cartoon and family oriented movies had little immediate impact on beliefs about smoking in preadolescent children, but a significant cumulative impact on norms cannot be ruled out. PMID- 22778303 TI - Choriophobia: a 1-act play. AB - The management of a newborn born to a mother with chorioamnionitis is controversial. By using data collected on neonates born in the era of routine maternal screening for Group B Streptococcus, we calculate that the risk of early onset sepsis in a hypothetical infant born at term to a mother with chorioamnionitis, who has a normal physical examination at birth, is likely substantially <1% if the mother's screen for Group B Streptococcus was negative. This low rate of sepsis calls into question current guidelines recommending treatment of all such newborns with intravenous antibiotics for 48 hours pending the results of a blood culture. Current guidelines for the management of infants born to mothers with chorioamnionitis also raise an important ethical issue; the recommendation to treat these infants with intravenous antibiotics is, in essence, a de facto determination of what constitutes unacceptable risk to the newborn. We argue that this determination is ultimately value-based and therefore requires broader deliberation than that which frequently occurs among medical experts who develop medical guidelines. PMID- 22778304 TI - Malonyl coenzyme A decarboxylase deficiency: early dietary restriction and time course of cardiomyopathy. AB - Malonyl coenzyme A (CoA) decarboxylase (MCD) deficiency is a rare autosomal recessive organic acidemia characterized by varying degrees of organ involvement and severity. MCD regulates fatty acid biosynthesis and converts malonyl-CoA to acetyl-CoA. Cardiomyopathy is 1 of the leading causes of morbidity and mortality in this disorder. It is unknown if diet alone prevents cardiomyopathy development based in published literature. We report a 10-month-old infant girl identified by newborn screening and confirmed MCD deficiency with a novel homozygous MLYCD mutation. She had normal echocardiogram measurements before transition to high medium-chain triglycerides and low long-chain triglycerides diet. Left ventricular noncompaction development was not prevented by dietary interventions. Further restriction of long-chain triglycerides and medium-chain triglycerides supplementation in combination with angiotensin-converting enzyme inhibitors helped to improve echocardiogram findings. Patient remained asymptomatic, with normal development and growth. Our case emphasizes the need for ongoing cardiac disease screening in patients with MCD deficiency and the benefits and limitations of current dietary interventions. PMID- 22778305 TI - Influence of motion picture rating on adolescent response to movie smoking. AB - OBJECTIVE: To examine the association between movie smoking exposure (MSE) and adolescent smoking according to rating category. METHODS: A total of 6522 US adolescents were enrolled in a longitudinal survey conducted at 8-month intervals; 5503 subjects were followed up at 8 months, 5019 subjects at 16 months, and 4575 subjects at 24 months. MSE was estimated from 532 recent box office hits, blocked into 3 Motion Picture Association of America rating categories: G/PG, PG-13, and R. A survival model evaluated time to smoking onset. RESULTS: Median MSE in PG-13-rated movies was ~3 times higher than median MSE from R-rated movies, but their relation with smoking was essentially the same, with adjusted hazard ratios of 1.49 (95% confidence interval [CI]: 1.23-1.81) and 1.33 (95% CI: 1.23-1.81) for each additional 500 occurrences of MSE respectively. MSE from G/PG-rated movies was small and had no significant relationship with adolescent smoking. Attributable risk estimates showed that adolescent smoking would be reduced by 18% (95% CI: 14-21) if smoking in PG-13-rated movies was reduced to the fifth percentile. In comparison, making all parents maximally authoritative in their parenting would reduce adolescent smoking by 16% (95% CI: 12-19). CONCLUSIONS: The equivalent effect of PG-13-rated and R-rated MSE suggests it is the movie smoking that prompts adolescents to smoke, not other characteristics of R-rated movies or adolescents drawn to them. An R rating for movie smoking could substantially reduce adolescent smoking by eliminating smoking from PG-13 movies. PMID- 22778306 TI - FDA's health claim review: whey-protein partially hydrolyzed infant formula and atopic dermatitis. AB - In this review, we explain how the US Food and Drug Administration (FDA) used its evidence-based review system to evaluate the scientific evidence for a qualified health claim for 100% whey-protein partially hydrolyzed infant formula (W-PHF) and reduced risk of atopic dermatitis (AD). The labeling of health claims, including qualified health claims, on conventional foods and dietary supplements require premarket approval by the FDA. Health claims characterize the relationship between a substance (food or food component) and disease (eg, cancer or cardiovascular disease) or health-related condition (eg, hypertension). To determine whether sufficient evidence exists to support the qualified health claim, the FDA evaluated human intervention studies that evaluated the role of W PHF in reducing the risk of AD. The FDA concluded there is little to very little evidence, respectively, to support a qualified health claim concerning the relationship between intake of W-PHF and a reduced risk of AD in partially breastfed and exclusively formula-fed infants throughout the first year after birth and up to 3 years of age. In addition, the FDA required a warning statement be displayed along with the health claim to indicate to consumers that partially hydrolyzed infant formulas are not hypoallergenic and should not be fed to infants who are allergic to milk or to infants with existing milk allergy symptoms. PMID- 22778307 TI - Respiratory tract illnesses during the first year of life: effect of dog and cat contacts. AB - OBJECTIVES: To investigate the effect of dog and cat contacts on the frequency of respiratory symptoms and infections during the first year of life. METHODS: In this birth cohort study, 397 children were followed up from pregnancy onward, and the frequency of respiratory symptoms and infections together with information about dog and cat contacts during the first year of life were reported by using weekly diaries and a questionnaire at the age of 1 year. All the children were born in eastern or middle Finland between September 2002 and May 2005. RESULTS: In multivariate analysis, children having dogs at home were healthier (ie, had fewer respiratory tract symptoms or infections) than children with no dog contacts (adjusted odds ratio, [aOR]: 1.31; 95% confidence interval [CI]: 1.13 1.52). Furthermore, children having dog contacts at home had less frequent otitis (aOR: 0.56; 95% CI: 0.38-0.81) and tended to need fewer courses of antibiotics (aOR: 0.71; 95% CI: 0.52-0.96) than children without such contacts. In univariate analysis, both the weekly amount of contact with dogs and cats and the average yearly amount of contact were associated with decreased respiratory infectious disease morbidity. CONCLUSIONS: These results suggest that dog contacts may have a protective effect on respiratory tract infections during the first year of life. Our findings support the theory that during the first year of life, animal contacts are important, possibly leading to better resistance to infectious respiratory illnesses during childhood. PMID- 22778308 TI - Neonatal morbidities and developmental delay in moderately preterm-born children. AB - BACKGROUND AND OBJECTIVE: Children born moderately preterm (32-35(6/7) weeks' gestation) are at increased risk of both neonatal morbidities and developmental delays in early childhood. It is unknown whether neonatal morbidities contribute to the increased risk of developmental delay. The objective of this study was to determine the effect of neonatal morbidities after moderately preterm birth on development at preschool age. METHODS: In a community-based, stratified cohort, parents of 832 moderately preterm children born in 2002 or 2003 completed the Ages and Stage Questionnaire when their child was 43 to 49 months old. Data on Apgar scores, asphyxia, tertiary NICU admission, hospital transfer, circulatory insufficiency, hypoglycemia, septicemia, mechanical ventilation, continuous positive airway pressure, apneas, caffeine treatment, and hyperbilirubinemia were obtained from medical records. We assessed associations of neonatal characteristics with developmental delay, adjusted for gender, small-for gestational-age status, gestational age, and maternal education. RESULTS: Hypoglycemia and asphyxia were associated with developmental delay; odds ratios (ORs) were 2.42 (95% confidence interval [CI]: 1.23-4.77) and 3.18 (95% CI: 1.01 10.0), respectively. Tertiary NICU admission and hyperbilirubinemia had positive but statistically borderline nonsignificant associations with developmental delay: ORs were 1.74 (95% CI: 0.96-3.15) and 1.52 (95% CI: 0.94-2.46), respectively. No other neonatal morbidities were associated with developmental delay. In multivariate analyses, only hypoglycemia was associated with developmental delay (OR: 2.19; 95% CI: 1.08-4.46). CONCLUSIONS: In moderately preterm-born children, only hypoglycemia increased the risk of developmental delay at preschool age. A concerted effort to prevent hypoglycemia might enhance developmental outcome in this group. PMID- 22778309 TI - Clinical and radiographic characteristics associated with abusive and nonabusive head trauma: a systematic review. AB - BACKGROUND AND OBJECTIVE: To systematically review the literature to determine which clinical and radiographic characteristics are associated with abusive head trauma (AHT) and nonabusive head trauma (nAHT) in children. METHODS: We searched MEDLINE, EMBASE, PubMed, conference proceedings, and reference lists to identify relevant studies. Two reviewers independently selected studies that compared clinical and/or radiographic characteristics including historical features, physical exam and imaging findings, and presenting signs or symptoms in hospitalized children <= 6 years old with AHT and nAHT. RESULTS: Twenty-four studies were included. Meta-analysis was complicated by inconsistencies in the reporting of characteristics and high statistical heterogeneity. Notwithstanding these limitations, there were 19 clinical and radiographic variables that could be meta-analyzed and odds ratios were determined for each variable. In examining only studies deemed to be high quality, we found that subdural hemorrhage(s), cerebral ischemia, retinal hemorrhage(s), skull fracture(s) plus intracranial injury, metaphyseal fracture(s), long bone fracture(s), rib fracture(s), seizure(s), apnea, and no adequate history given were significantly associated with AHT. Epidural hemorrhage(s), scalp swelling, and isolated skull fracture(s) were significantly associated with nAHT. Subarachnoid hemorrhage(s), diffuse axonal injury, cerebral edema, head and neck bruising, any bruising, and vomiting were not significantly associated with either type of trauma. CONCLUSIONS: Clinical and radiographic characteristics associated with AHT and nAHT were identified, despite limitations in the literature. This systematic review also highlights the need for consistent criteria in identifying and reporting clinical and radiographic characteristics associated with AHT and nAHT. PMID- 22778310 TI - The evolution of the child maltreatment literature. PMID- 22778311 TI - American Society of Clinical Oncology Clinical Practice Guidelines: formal systematic review-based consensus methodology. AB - The American Society of Clinical Oncology (ASCO) guidelines program employs a systematic review-based methodology to produce evidence-based guidelines. This is consistent with the stance of the Institute of Medicine on guideline development, which is that high-quality evidence syntheses form the basis for recommendation development. In the absence of high-quality evidence, recommendation development becomes more complex. One option is to provide no recommendations or withdraw a guideline topic. However, it is often the areas of greatest uncertainty in which the evidentiary base is incomplete, and thus, guidelines are needed most. To provide recommendations in such circumstances, an explicit methodology is needed to ensure that a credible process is undertaken, and rigorous, reliable advice is provided. In 2010, the ASCO Board of Directors approved development of guideline recommendations using consensus methodology. A modified Delphi approach to recommendation development, based on the best available data identified in a systematic review, was piloted with an ASCO guideline. Consensus was achieved through the rating of a series of recommendations by a large group of clinicians, including academic and community-based content and methodology experts. A prespecified threshold of agreement was determined to indicate when consensus was achieved. Consensus was defined as agreement by >= 75% of raters. The formal consensus methodology used by ASCO enabled development of guideline recommendations on a challenging clinical issue based on limited evidence using a rigorous, transparent, and explicit method. This methodology is proposed for development of future ASCO guidelines on topics for which limited evidence is available. PMID- 22778312 TI - Change in working time in a population-based cohort of patients with breast cancer. AB - PURPOSE: We examined changes in working time 16 months after a breast cancer diagnosis and identified factors associated with job discontinuation and/or decreased working time. PATIENTS AND METHODS: This was a population-based cohort study with 735 patients identified in the Regional Breast Cancer Quality Register of Central Sweden. The study sample consisted of 505 women (age < 63 years at diagnosis) who completed questionnaires at baseline and at follow-up (on average 4 and 16 months after diagnosis, respectively). Clinical register data and questionnaire data on sociodemographic factors were obtained at baseline. Self reported work-related data were obtained at follow-up. Odds ratios were estimated by using logistic regression models. RESULTS: Compared with prediagnosis working time, 72% reported no change in working time, 2% reported an increase, 15% reported a decrease, and 11% did not work at follow-up. Chemotherapy increased the likelihood (odds ratio [OR], 2.45; 95% CI, 1.38 to 4.34) of job discontinuation/decreased working time. Among chemotherapy recipients, associated factors included full-time work prediagnosis (OR, 3.25; 95% CI, 1.51 to 7.01), cancer-related work limitations (OR, 5.26; 95% CI, 2.30 to 12.03), and less value attached to work (OR, 3.69; 95% CI, 1.80 to 7.54). In the nonchemotherapy group, older age (OR, 1.09; 95% CI, 1.02 to 1.17) and less value attached to work (OR, 5.00; 95% CI, 2.01 to 12.45) were associated with the outcome. CONCLUSION: The majority of women treated for breast cancer returned to their prediagnosis working time. Chemotherapy and cancer-related work limitations are important factors to take into account in identifying women in need of support. Moreover, it is important to consider the woman's own valuation of labor market participation. PMID- 22778313 TI - Early diagnosis of acute myeloid leukemia by computed tomography scan. PMID- 22778314 TI - Advance care planning in patients with cancer referred to a phase I clinical trials program: the MD Anderson Cancer Center experience. AB - PURPOSE: Patients with advanced malignancies referred for early clinical trials have a short life expectancy. We designed this survey to ascertain the status of advance care planning in this population. PATIENTS AND METHODS: Patients who were seen in a phase I clinic were asked to anonymously complete an investigator designed survey. RESULTS: Of 435 individuals approached, 215 (49%) returned completed or partially completed surveys, whereas many others stated that they wanted to avoid the topic, because they had come to the phase I clinic for cancer therapy. Most patients (n = 149; 69%) were still hopeful about their future. Approximately 42% of patients (n = 90) reported having a living will, 46% had a medical power of attorney (n = 98), and 19% had a do-not-resuscitate (DNR) order (n = 40). Approximately 20% of participants (n = 43) had not discussed advance care planning. Fifty-nine percent of patients wanted to discuss advance care planning with their physician. Having a DNR order in place was significantly more common in individuals who had a living will and/or a medical power of attorney. CONCLUSION: Although most patients referred to a phase I clinic remained optimistic, many had discussed a living will, medical power of attorney, and/or DNR order with their physician, family, and/or attorney. However, a significant minority had not addressed this issue with anyone, and many refused to take a survey on the topic. More than half of the patients wanted to discuss these matters with their physician. These observations suggest that extra effort to address advance care planning is needed for these patients. PMID- 22778315 TI - Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway. AB - Agents inhibiting the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin (PAM) pathway are currently in various stages of clinical development in oncology, ranging from some in early-phase evaluations to others that have already received regulatory approval for treatment in advanced cancers. The administration of PAM pathway inhibitors has been associated with metabolic toxicities of hyperlipidemia and hyperglycemia. The PAM Task Force of the National Cancer Institute Investigational Drug Steering Committee convened an interdisciplinary expert panel to review the pathophysiology of hyperlipidemia and hyperglycemia induced by PAM pathway inhibitors, summarize the incidence of these metabolic toxicities induced by such agents in the current literature, advise on clinical trial screening and monitoring criteria, and provide management guidance and therapeutic goals on occurrence of these toxicities. The overarching aim of this consensus report is to raise awareness of these metabolic adverse events to enable their early recognition, regular monitoring, and timely intervention in clinical trials. Hyperglycemia and hyperlipidemia are generally not acutely toxic and most often reversible with therapeutic intervention. Dose modifications or discontinuation of PAM pathway inhibitors should only be considered in situations of severe events or if progressive metabolic derangement persists after therapeutic interventions have been attempted for a sufficient duration. Specialty consultation should be sought to aid clinical trial planning and the management of these metabolic adverse events. PMID- 22778316 TI - A lobectomy by any other name. PMID- 22778317 TI - First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial. AB - PURPOSE: Erlotinib prolonged survival of unselected patients with advanced non small-cell lung cancer (NSCLC) who were not eligible for further chemotherapy, and two phase II studies suggested it might be an alternative to first-line chemotherapy. A randomized phase III trial was designed to test whether first line erlotinib followed at progression by cisplatin-gemcitabine was not inferior in terms of survival to the standard inverse sequence. PATIENTS AND METHODS: Patients with stage IIIB (with pleural effusion or supraclavicular nodes) to IV NSCLC and performance status of 0 to 1 were eligible. With a 95% CI upper limit of 1.25 for the hazard ratio (HR) for death, 80% power, a one-sided alpha = .025, and two interim analyses, a sample size of 900 patients was planned. RESULTS: At the first planned interim analysis with half the events, the inferiority boundary was crossed, and the Independent Data Monitoring Committee recommended early termination of the study. Seven hundred sixty patients (median age, 62 years; range, 27 to 81 years) had been randomly assigned. Baseline characteristics were balanced between study arms. As of June 1, 2011, median follow-up was 24.3 months, and 536 deaths were recorded (263 in the standard treatment arm and 273 in the experimental arm). Median survival was 11.6 months (95% CI, 10.2 to 13.3 months) in the standard arm and 8.7 months (95% CI, 7.4 to 10.5 months) in the experimental arm. Adjusted HR of death in the experimental arm was 1.24 (95% CI, 1.04 to 1.47). There was no heterogeneity across sex, smoking habit, histotype, and epidermal growth factor receptor (EGFR) mutation. CONCLUSION: In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib. PMID- 22778318 TI - Incomplete intrapulmonary lymph node retrieval after routine pathologic examination of resected lung cancer. AB - PURPOSE: Pathologic nodal stage affects prognosis in patients with surgically resected non-small-cell lung cancer (NSCLC). Unlike examination of mediastinal lymph nodes (LNs), which depends on surgical practice, accurate examination of intrapulmonary (N1) nodes depends primarily on pathology practice. We investigated the completeness of N1 LN examination in NSCLC resection specimens and its potential impact on stage. PATIENTS AND METHODS: We performed a case control study of a special pathologic examination (SPE) protocol using thin gross dissection with retrieval and microscopic examination of all LN-like material on remnant NSCLC resection specimens after routine pathologic examination (RPE). We compared LNs retrieved by the SPE protocol with nodes examined after RPE of the same lung specimens and with those of an external control cohort. RESULTS: We retrieved additional LNs in 66 (90%) of 73 patient cases and discovered metastasis in 56 (11%) of 514 retrieved LNs from 27% of all patients. We found unexpected LN metastasis in six (12%) of 50 node-negative patients. Three other patients had undetected satellite metastatic nodules. Pathologic stage was upgraded in eight (11%) of 73 patients. The time required for the SPE protocol decreased significantly with experience, with no change in the number of LNs found. CONCLUSION: Standard pathology practice frequently leaves large numbers of N1 LNs unexamined, a clinically significant proportion of which harbor metastasis. By improving N1 LN examination, SPE can have an impact on prognosis and adjuvant management. We suggest adoption of the SPE to improve pathologic staging of resected NSCLC. PMID- 22778319 TI - Polyclonal serum free light chains: a biomarker of disease prognosis or of immune senescence? PMID- 22778320 TI - Prospective study of bevacizumab plus temozolomide in patients with advanced neuroendocrine tumors. AB - PURPOSE: Both tyrosine kinase inhibitors targeting the vascular endothelial growth factor (VEGF) receptor and bevacizumab, a monoclonal antibody targeting VEGF, have antitumor activity in neuroendocrine tumors (NETs). Temozolomide, an oral analog of dacarbazine, also has activity against NETs when administered alone or in combination with other agents. We performed a phase II study to evaluate the efficacy of temozolomide in combination with bevacizumab in patients with locally advanced or metastatic NETs. PATIENTS AND METHODS: Thirty-four patients (56% with carcinoid, 44% with pancreatic NETs) were treated with temozolomide 150 mg/m(2) orally per day on days 1 through 7 and days 15 through 21, together with bevacizumab at a dose of 5 mg/kg per day intravenously on days 1 and 15 of each 28-day cycle. All patients received prophylaxis against Pneumocystis carinii and varicella zoster. Patients were followed for toxicity, biochemical and radiologic response, and survival. RESULTS: The combination of temozolomide and bevacizumab was associated with anticipated grade 3 to 4 toxicities, including lymphopenia (53%) and thrombocytopenia (18%). Although the overall radiographic response rate was 15% (five of 34), response rates differed between patients with pancreatic NETs (33%; five of 15) and those with carcinoid tumors (zero of 19). The median progression-free survival was 11.0 months (14.3 months for pancreatic NETs v 7.3 months for carcinoid tumors). The median overall survival was 33.3 months (41.7 months for pancreatic NETs v 18.8 months for carcinoid tumors). CONCLUSION: Temozolomide and bevacizumab can be safely administered together in patients with advanced NETs, and the combination regimen appears promising for patients with pancreatic NETs. Studies evaluating the relative contributions of these two agents to the observed antitumor activity are warranted. PMID- 22778321 TI - Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline. AB - PURPOSE: The American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) sought to provide an evidence-based guideline on the use of lymphatic mapping and sentinel lymph node (SLN) biopsy in staging patients with newly diagnosed melanoma. METHODS: A comprehensive systematic review of the literature published from January 1990 through August 2011 was completed using MEDLINE and EMBASE. Abstracts from ASCO and SSO annual meetings were included in the evidence review. An Expert Panel was convened to review the evidence and develop guideline recommendations. RESULTS: Seventy-three studies met full eligibility criteria. The evidence review demonstrated that SLN biopsy is an acceptable method for lymph node staging of most patients with newly diagnosed melanoma. RECOMMENDATIONS: SLN biopsy is recommended for patients with intermediate-thickness melanomas (Breslow thickness, 1 to 4 mm) of any anatomic site; use of SLN biopsy in this population provides accurate staging. Although there are few studies focusing on patients with thick melanomas (T4; Breslow thickness, > 4 mm), SLN biopsy may be recommended for staging purposes and to facilitate regional disease control. There is insufficient evidence to support routine SLN biopsy for patients with thin melanomas (T1; Breslow thickness, < 1 mm), although it may be considered in selected patients with high-risk features when staging benefits outweigh risks of the procedure. Completion lymph node dissection (CLND) is recommended for all patients with a positive SLN biopsy and achieves good regional disease control. Whether CLND after a positive SLN biopsy improves survival is the subject of the ongoing Multicenter Selective Lymphadenectomy Trial II. PMID- 22778322 TI - Who provides psychosocial follow-up care for post-treatment cancer survivors? A survey of medical oncologists and primary care physicians. AB - PURPOSE: Addressing psychosocial needs, including key components of psychologic distress, physical symptoms, and health promotion, is vital to cancer follow-up care. Yet little is known about who provides psychosocial care. This study examined physician-reported practices regarding care of post-treatment cancer survivors. We sought to characterize physicians who reported broad involvement in (ie, across key components of care) and shared responsibility for psychosocial care. METHODS: A nationally representative sample of medical oncologists (n = 1,130) and primary care physicians (PCPs; n = 1,021) were surveyed regarding follow-up care of breast and colon cancer survivors. RESULTS: Approximately half of oncologists and PCPs (52%) reported broad involvement in psychosocial care. Oncologist and PCP confidence, beliefs about who is able to provide psychosocial support, and preferences for shared responsibility for care predicted broad involvement. However, oncologists' and PCPs' perceptions of who provides specific aspects of psychosocial care differed (P < .001); both groups saw themselves as the main providers. Oncologists' confidence, PCPs' beliefs about who is able to provide psychosocial support, and oncologist and PCP preference for models other than shared care were inversely associated with a shared approach to care. CONCLUSION: Findings that some providers are not broadly involved in psychosocial care and that oncologists and PCPs differ in their beliefs regarding who provides specific aspects of care underscore the need for better care coordination, informed by the respective skills and desires of physicians, to ensure needs are met. Interventions targeting physician confidence, beliefs about who is able to provide psychosocial support, and preferred models for survivorship care may improve psychosocial care delivery. PMID- 22778323 TI - Novel targeted agents and the need to refine clinical end points in chronic lymphocytic leukemia. PMID- 22778324 TI - Transarterial chemoembolization of liver metastases as symptomatic therapy of lipase hypersecretion syndrome. PMID- 22778325 TI - The unique saga of PEPFAR and its phenomenal potential. PMID- 22778326 TI - The President's Emergency Plan for AIDS Relief: from successes of the emergency response to challenges of sustainable action. AB - The President's Emergency Plan for AIDS Relief (PEPFAR) has made a major contribution to the reduction of the global HIV/AIDS burden. The program initially focused on rapidly scaling up treatment and prevention services in fifteen low-income countries, then transitioned to an approach that emphasizes sustainability, defined as the capacity to maintain program services after financial, managerial, and technical assistance from the United States and other external donors essentially ceases. Today, PEPFAR continues to expand its HIV prevention, treatment, and care activities while also supporting capacity building initiatives, coordination efforts, and implementation science. The latter is research focused on improving service delivery, maximizing cost effectiveness, and achieving public health impact. Recent advances in both scientific knowledge and the provision of prevention, treatment, and care services have bred cautious optimism about greatly reducing the spread of HIV. However, success will require a substantial increase in resources, strengthened health systems, renewed commitment to HIV prevention, and well-financed efforts to develop an effective HIV vaccine. PMID- 22778327 TI - The President's Emergency Plan for AIDS Relief: how George W. Bush and aides came to 'think big' on battling HIV. PMID- 22778328 TI - Lessons from the President's Emergency Plan for AIDS Relief: from quick ramp-up to the role of strategic partnership. AB - In its first five years, the President's Emergency Plan for AIDS Relief (PEPFAR)- the largest commitment ever by any nation to combat a single disease--succeeded in getting 2.1 million people on antiretroviral treatment and 10.1 million people in care; prevented an estimated 237,600 HIV infections in infants; and saved an estimated 3.28 million adult years of life. Much of the global program's success can be attributed to early decisions to implement new structures and approaches designed to meet its ambitious targets quickly, overcome bureaucratic inertia, and ensure continued progress. A unified US government program was created with a single coordinator. There was a focus on quick ramp-up, strategic partnerships, and sustainable local ownership. Accountability and performance were emphasized. These new approaches played critical roles in translating the unprecedented resources and political support for PEPFAR into improved health for millions of people. Successful aspects of the way in which PEPFAR was organized and implemented, along with less successful or deficient ones, offer lessons for any large, complex international health initiative. PMID- 22778329 TI - HIV donor funding has both boosted and curbed the delivery of different non-HIV health services in sub-Saharan Africa. AB - Donor funding for HIV programs has increased rapidly over the past decade, raising questions about whether other health services in recipient-country health systems are being crowded out or strengthened. This article--an investigation of the impacts of increased HIV donor funding on non-HIV health services in sub Saharan Africa during 2003-10--provides evidence of both effects. HIV aid in some countries has crowded out the delivery of childhood immunizations, especially in countries with the lowest density of health care providers. At the same time, HIV aid may have positively affected some maternal health services, such as prenatal blood testing. These mixed results suggest that donors should be more attentive to domestic resource constraints, such as limited numbers of health workers; should integrate more fully with existing health systems; and should address these constraints up front to limit possible negative effects on the delivery of other health services. PMID- 22778330 TI - Lessons learned from a decade of partnership between PEPFAR and the Global Fund: a case study from Tanzania. AB - The President's Emergency Plan for AIDS Relief was intended to be complementary to existing US work to fight HIV/AIDS through the broader multilateral efforts of the Global Fund to Fight AIDS, Tuberculosis, and Malaria. This article explores the history of this collaboration, highlighting lessons learned through a case study of Tanzania and challenges overcome through ongoing improvements, such as ensuring reliable access to antiretroviral drugs. Improved communication and a more formalized partnership between PEPFAR's bilateral efforts and the Global Fund have been key to improving health outcomes in Tanzania, and this case can be used as a model for other countries. If PEPFAR is reauthorized in 2013, its partnership with the Global Fund should be further formalized and expanded. PMID- 22778331 TI - A clinician's experience with the President's Emergency Plan for AIDS Relief in Nigeria: a transformative decade of hope. AB - Prior to the start of the President's Emergency Plan for AIDS Relief (PEPFAR), Nigeria struggled to fight HIV/AIDS. PEPFAR changed everything. I witnessed this change firsthand by directing the response to AIDS, first in my hospital in Jos, in central Nigeria, and now as Nigeria's HIV/AIDS coordinator. When the first AIDS case was diagnosed in Nigeria in 1986, my country had one of the world's poorest health systems, and as the pandemic spread, most Nigerians with AIDS died. Eventually, effective new drugs were developed, but they were too costly for all but a few Nigerians. Then there was a miracle: PEPFAR gave us resources, direction, and expertise to treat hundreds of thousands of people around the country. Today, Nigeria is providing treatment to 500,000 people with AIDS, and 80 percent of them receive treatment supported by PEPFAR. The US effort did more than help us treat people with HIV/AIDS; it also enabled Nigeria to strengthen its health system, improve care for pregnant women and infants, increase the provision of vaccinations, build modern laboratories, and train thousands of new health care workers and technicians. PMID- 22778332 TI - Low-cost generic drugs under the President's Emergency Plan for AIDS Relief drove down treatment cost; more are needed. AB - The President's Emergency Plan for AIDS Relief (PEPFAR) was originally authorized in 2003 with the goal of supporting HIV prevention, treatment, and care within fifteen focus countries in the developing world. By September 2011 nearly 13 million people around the world were receiving HIV/AIDS-related care through PEPFAR, and 3.9 million were receiving antiretroviral treatment. However, in the early years of the program, access to antiretroviral drugs was hampered by the lack of a licensing process that the US government recognized for generic versions of these medications. Ultimately, the obstacle to approval of generic antiretroviral drugs was removed, which led to PEPFAR's considerable success at making these treatments widely available. This article outlines PEPFAR's evolving use of generic antiretroviral drugs to treat HIV in the developing world, highlights ongoing initiatives to increase access to generic antiretrovirals, and points to the need for mechanisms that will speed up the approval of new generic drugs. The striking decline in antiretroviral treatment costs, from $1,100 per person annually in 2004 to $335 per person annually in 2012, is due to the availability of effective generic antiretrovirals. Given growing resistance to existing drugs and the planned expansion of treatment to millions more people, access to newer generations of generic antiretrovirals will have to be expedited. PMID- 22778333 TI - HIV treatment as prevention: how scientific discovery occurred and translated rapidly into policy for the global response. AB - In 2011 interim results of HIV Prevention Trials Network study 052, a National Institutes of Health study designed to test the effectiveness of antiretroviral treatment against the spread of HIV, were reported. These results showed that in a stable relationship in which one member of the couple was infected with HIV, treatment of the infected partner with antiretroviral drugs, combined with couples counseling and condom use, resulted in a 96 percent reduction in sexual transmission of HIV-1. This finding led to the use of antiretroviral treatment as a cornerstone of HIV prevention. Independent advisory committees of the President's Emergency Plan for AIDS Relief (PEPFAR) and the World Health Organization (WHO) have since issued analyses that set the stage for broader use of antiretroviral agents in treatment and prevention. This article describes the separate PEPFAR and WHO recommendations and outlines the design of prospective new trials to test how best to maximize the benefits of early treatment for prevention. PMID- 22778334 TI - How PEPFAR's public-private partnerships achieved ambitious goals, from improving labs to strengthening supply chains. AB - The President's Emergency Plan for AIDS Relief (PEPFAR), established in 2003, is widely recognized as one of the most ambitious and successful bilateral programs ever implemented to address a single disease. Part of the program's success is attributable to the participation of the private sector, working in partnership with the US and local governments and implementing organizations to maximize the reach and effectiveness of every dollar spent. We examined key public-private partnerships that grew out of PEPFAR to identify features that have made them effective. For example, PEPFAR's Supply Chain Management System took advantage of private industry's best practices in logistics, and a partnership with the medical technology company BD (Becton, Dickinson and Company) improved laboratory systems throughout sub-Saharan Africa. We found that setting ambitious goals, enlisting both global and local partners, cultivating a culture of collaboration, careful planning, continuous monitoring and evaluation, and measuring outcomes systematically led to the most effective programs. The Office of the US Global AIDS Coordinator and PEPFAR should continue to strengthen their capacity for private-sector partnerships, learning from a decade of experience and identifying new ways to make smart investments that will make the most efficient use of taxpayer resources, expand proven interventions more rapidly, and help ensure the sustainability of key programs. PMID- 22778335 TI - In a study of a population cohort in South Africa, HIV patients on antiretrovirals had nearly full recovery of employment. AB - Antiretroviral therapy for HIV may have important economic benefits for patients and their households. We quantified the impact of HIV treatment on employment status among HIV patients in rural South Africa who were enrolled in a public sector HIV treatment program supported by the President's Emergency Plan for AIDS Relief. We linked clinical data from more than 2,000 patients in the treatment program with ten years of longitudinal socioeconomic data from a complete community-based population cohort of more than 30,000 adults residing in the clinical catchment area. We estimated the employment effects of HIV treatment in fixed-effects regressions. Four years after the initiation of antiretroviral therapy, employment among HIV patients had recovered to about 90 percent of baseline rates observed in the same patients three to five years before they started treatment. Many patients initiated treatment early enough that they were able to avoid any loss of employment due to HIV. These results represent the first estimates of employment recovery among HIV patients in a general population, relative to the employment levels that these patients had prior to job-threatening HIV illness and the decision to seek care. There are large economic benefits to HIV treatment. For some patients, further gains could be obtained from initiating antiretroviral therapy earlier, prior to HIV-related job loss. PMID- 22778337 TI - PEPFAR programs linked to more deliveries in health facilities by African women who are not infected with HIV. AB - HIV programs in lower-income countries have provided lifesaving care and treatment to millions of people, but their expansion has raised concerns that these programs may have diverted health workers, management attention, and infrastructure investments from other health priorities, such as high maternal mortality in sub-Saharan Africa. We assessed the effect of HIV programs supported by the President's Emergency Plan for AIDS Relief (PEPFAR) on maternal health services for women not infected with HIV in 257 health facilities in eight African countries in 2007-11. Controlling for other variables, we found that having more patients on antiretroviral treatment and HIV-related infrastructure investments, such as on-site laboratories at health clinics, were associated with more deliveries at health facilities by women not infected with HIV. This association is consistent with the hypothesis that PEPFAR-funded infrastructure may also support other health services and that the program may have laid the foundation for improving health system performance in maternal health overall. We recommend that lessons learned from the rapid expansion of HIV services in sub Saharan Africa should be drawn on to increase the provision of maternal and newborn health care and other high-priority health services, such as the treatment of diabetes, hypertension, and other chronic, noncommunicable diseases. PMID- 22778336 TI - HIV treatment produces economic returns through increased work and education, and warrants continued US support. AB - Federal expenditures are under scrutiny in the United States, and the merits of continuing and expanding the President's Emergency Plan for AIDS Relief (PEPFAR) to support access to antiretroviral therapy have become a topic of debate. A growing body of research on the economic benefits of treatment with antiretroviral therapy has important implications for these discussions. For example, research conducted since the inception of PEPFAR shows that HIV-infected adults who receive antiretroviral therapy often begin or resume productive work, and that children living in households with infected adults who are on treatment are more likely to attend school than those in households with untreated adults. These benefits should be considered when weighing the overall benefits of providing antiretroviral therapy against its costs, particularly in the context of discussions about the future of PEPFAR. A modest case can also be made in favor of having private companies in HIV-affected countries provide antiretroviral therapy to their employees and dependents, thus sharing some of the burden of funding HIV treatment. PMID- 22778338 TI - Eliminating mother-to-child HIV transmission will require major improvements in maternal and child health services. AB - Although some low- and middle-income countries have made progress toward eliminating mother-to-child transmission of HIV, others lack health systems that can deliver accessible and reliable care. We modeled how access to maternal and child health services and the effective delivery of interventions would affect efforts to eliminate HIV transmission during pregnancy and after childbirth in low- and middle-income countries. In countries with high HIV rates, our model predicts transmission rates of 19.7 percent at current levels of access and efficiency of maternal and child health and HIV treatment. Even if current treatment programs were carried out at or near perfect levels, we predict that significant residual mother-to-child transmission (7.9 percent) would remain. The model suggests that under current conditions, poor access to routine health services contributes three times more to overall mother-to-child HIV transmission than do current suboptimal levels of efficiency of anti-HIV-transmission interventions. We conclude that current efforts to optimize programs to prevent mother-to-child HIV transmission will not, on their own, eliminate HIV in newborns. Access to maternal and child health services will need to be dramatically improved, as will prevention measures, such as identifying and treating HIV before pregnancy. PMID- 22778339 TI - Investing in HIV services while building Kenya's health system: PEPFAR's support to prevent mother-to-child HIV transmission. AB - Trade-offs may exist between investments to promote health system strengthening, such as investments in facilities and training, and the rapid scale-up of HIV/AIDS services. We analyzed trends in expenditures to support the prevention of mother-to-child transmission of HIV in Kenya under the President's Emergency Plan for AIDS Relief (PEPFAR) from 2005 to 2010. We examined how expenditures changed over time, considering health system strengthening alongside direct treatment of patients. We focused on two organizations carrying out contracts under PEPFAR: the Elizabeth Glaser Pediatric AIDS Foundation and FHI360 (formerly Family Health International), a nonprofit health and development organization. We found that the average unit expenditure, or the spending on goods and services per mother living with HIV who was provided with antiretroviral drugs, declined by 52 percent, from $567 to $271, during this time period. The unit expenditure per mother-to-infant transmission averted declined by 66 percent, from $7,117 to $2,440. Meanwhile, the health system strengthening proportion of unit expenditure increased from 12 percent to 33 percent during the same time period. The analysis suggests that PEPFAR investments in prevention of mother-to-child transmission of HIV in Kenya became more efficient over time, and that there was no strong evidence of a trade-off between scaling up services and investing in health systems. PMID- 22778340 TI - PEPFAR's support for orphans and vulnerable children: some beneficial effects, but too little data, and programs spread thin. AB - Sixteen million children in developing and middle-income countries have been orphaned by HIV/AIDS, and at least another million children per year are rendered vulnerable by parental HIV/AIDS-related illness. Since 2003 the US government has provided approximately $1.6 billion to give four million of these children care and support through the President's Emergency Plan for AIDS Relief (PEPFAR). We conducted five studies to evaluate the effectiveness of PEPFAR's interventions for such children in East Africa and southern Africa. We found evidence of beneficial changes in school enrollment rates and on the psychosocial well-being of children. However, we could not demonstrate empirically the impact of most of the PEPFAR initiatives that we examined, primarily because of a lack of baseline data and clear outcome and impact indicators. We also found that many programs were spread so thin across a vulnerable population that little in the way of services actually reached beneficiaries, which raises questions about whether PEPFAR funds are sufficient, or if the program is attempting to do much with too few resources. We offer several recommendations, including better measuring the effect of programs for orphans and vulnerable children by collecting baseline data and conducting well-designed, rigorous outcome and impact evaluations. PMID- 22778341 TI - Countries where HIV is concentrated among most-at-risk populations get disproportionally lower funding from PEPFAR. AB - The legislation reauthorizing the President's Emergency Plan for AIDS Relief (PEPFAR) in 2008 recognized the need for HIV/AIDS programs directed to most-at risk populations, including men who have sex with men and people who inject drugs. To examine whether that goal is being met, we analyzed data from PEPFAR's Operational Plans for fiscal years 2009 and 2010. The eighteen countries in our study accounted for nearly two-thirds of overall PEPFAR financing for those fiscal years and approximately 60 percent of the total number of people living with HIV in the world in 2010. After controlling in each country for the number of people living with HIV, total population, and per capita income, we found that countries where HIV transmission occurs primarily among men who have sex with men and people who inject drugs received on average $235 million less in 2009 and 2010 than countries with widespread HIV epidemics among the general population. These findings raise questions about whether the country allocations of PEPFAR fully address needs based on the epidemiology of HIV infection in individual countries. Administrators should ensure that funding allocations directed to various countries reflect the best epidemiological data and latest science and best practices, and are devoid of bias against most-at-risk populations; they should also be more transparent about where PEPFAR's dollars go. Otherwise, it is unlikely that PEPFAR will realize its established goal of achieving an AIDS-free generation. PMID- 22778342 TI - The world must build on three decades of scientific advances to enable a new generation to live free of HIV/AIDS. AB - The extraordinary scientific advances made in the past three decades to understand, treat, and prevent HIV infection have contributed to the hope that a world free of AIDS is achievable. The growing armamentarium of scientifically proven interventions-including the use of antiretroviral medications to treat and prevent HIV infection, voluntary medical male circumcision, education and counseling about HIV risk and behavior change, condom use, drug and alcohol treatment, and needle exchange programs for injection drug users-offers an unprecedented opportunity to make major gains in the fight against HIV/AIDS. Combining and implementing these interventions as effectively as possible has the potential to dramatically change the trajectory of the HIV/AIDS pandemic. Substantive challenges remain, especially obtaining sufficient funding for HIV related interventions and developing the operational capacity to deliver them cost-effectively to all in need. If these challenges can be met, the world will have a clear path toward an "AIDS-free generation" in which new HIV infections, as well as illness and death due to AIDS, are increasingly rare. PMID- 22778343 TI - Given financial constraints, it would be unethical to divert antiretroviral drugs from treatment to prevention. AB - Striking advances in HIV prevention have set the stage for renewed debate on setting priorities in the fight against HIV/AIDS. Two new prevention strategies- preexposure prophylaxis and treatment as prevention--use antiretroviral drugs for prevention of HIV/AIDS in addition to treating patients. The potential for success of these new prevention strategies sets up an ethical dilemma: where resources are limited and supplies of lifesaving antiretroviral medications are insufficient to treat those currently living with HIV, how should these resources be divided between treatment and prevention? This article explores several ethical principles used in formulating public health policy. Assuming that limited resources are available for spending on drugs, we conclude that it would be unethical to watch patients with treatable AIDS worsen and die, even with supportive care, so that medications for treatment can be diverted for prevention. PMID- 22778344 TI - The 'third wave' of HIV prevention: filling gaps in integrated interventions, knowledge, and funding. AB - There is growing optimism in the global health community that the HIV epidemic can be halted. After decades of relying primarily on behavior change to prevent HIV transmission, a second generation of prevention efforts based on medical or biological interventions such as male circumcision and preexposure prophylaxis- the use of antiretroviral drugs to protect uninfected, at-risk individuals--has shown promising results. This article calls for a third generation of HIV prevention efforts that would integrate behavioral, biological, and structural interventions focused on the social, political, and environmental underpinnings of the epidemic, making use of local epidemiological evidence to target affected populations. In this third wave, global programs should deliver HIV prevention services together with cost-effective interventions for reproductive health and for tuberculosis, malaria, and other diseases. Additionally, new efforts are needed to address gaps in HIV prevention research, evaluation, and implementation. Increased and sustained funding, along with evidence-based allocation of funds, will be necessary to accelerate the decline in new HIV infections. PMID- 22778345 TI - PEPFAR's past and future efforts to cut costs, improve efficiency, and increase the impact of global HIV programs. AB - Amid the global economic crisis, the President's Emergency Plan for AIDS Relief (PEPFAR) and other organizations have been pressed to do more with constrained resources to meet unmet needs in the worldwide HIV/AIDS pandemic. PEPFAR has approached this challenge through the development of an Impact and Efficiency Acceleration Plan, which includes improving the collection and use of economic and financial data, increasing the efficiency of HIV/AIDS program implementation, and collaborating with governments and multilateral organizations to maximize the impact of the resources provided by the United States. For example, by linking financial data with program outputs, PEPFAR was able to help its implementing partners in Mozambique reduce mean unit expenditures for people receiving antiretroviral treatment by 45 percent, from $265 to $145 per person, between 2009 and 2011. This article describes the plan's elements, provides examples of progress and challenges to its implementation, and assesses the prospects for further improvements in efficiency and impact. PMID- 22778346 TI - The Medical Education Partnership Initiative: PEPFAR's effort to boost health worker education to strengthen health systems. AB - The early success of the President's Emergency Plan for AIDS Relief (PEPFAR) in delivering antiretroviral medications in poor countries unmasked the reality that many lacked sufficient health workers to dispense the drugs effectively. The 2008 reauthorization of PEPFAR embraced this challenge and committed to supporting the education and training of thousands of new health workers. In 2010 the program, with financial support from the US National Institutes of Health and administrative support from the Health Resources and Services Administration, launched the Medical Education Partnership Initiative to fund thirteen African medical schools and a US university. The US university would serve as a coordinating center to improve the quantity, quality, and retention of the schools' graduates. The program was not limited to training in the delivery of services for patients with HIV/AIDS. Rather, it was based on the principle that investment in medical education and retention would lead to health system strengthening overall. Although results are limited at this stage, this article reviews the opportunities and challenges of the first year of this major transnational medical education initiative and considers directions for future efforts and reforms, national governmental roles, and the sustainability of the program over time. PMID- 22778347 TI - The Global Health Strategy of the Department of Health and Human Services: building on the lessons of PEPFAR. AB - Building on its experience as a principal participant in the President's Emergency Plan for AIDS Relief, the Department of Health and Human Services has embarked on a new era of global initiatives that ultimately will protect the health of Americans. The Global Health Strategy announced by health and human services secretary Kathleen Sebelius in January 2012 recognizes that the health of Americans is intertwined with that of the rest of the world. The initiative features ten objectives that range from enhanced global health surveillance and preventing infectious diseases and health threats to health diplomacy. The Global Health Strategy is designed to make optimal use of the department's many specialty agencies and their considerable technical and programmatic expertise. The strategy moves beyond the President's Emergency Plan for AIDS Relief to redefine Health and Human Services' role outside US borders in addressing the health challenges of the twenty-first century. PMID- 22778348 TI - Four principles for expanding PEPFAR's role as a vital force in US health diplomacy abroad. AB - The President's Emergency Plan for AIDS Relief (PEPFAR) is the leading platform for US health diplomacy and a symbol of American capacity to achieve constructive and beneficial change. The program now faces an evolving context for its work that includes, on the one hand, domestic fiscal pressures in the United States, but on the other, the potential for substantial gains against the AIDS epidemic around the world. Continued success in advancing America's humanitarian and diplomatic interests through global health requires the United States to maintain robust investments in PEPFAR; implement a strategic plan to achieve an AIDS-free generation; use the program as a foundation to strengthen health systems generally and enable them to address broader health issues, such as chronic and noncommunicable diseases; carefully manage the transition to country "ownership" of the fight against HIV; and achieve greater coherence in US government health related policy. PMID- 22778349 TI - Replicating PEPFAR's success: how interventions shown to be effective abroad can be applied to the AIDS epidemic in the US. AB - The President's Emergency Plan for AIDS Relief (PEPFAR), which began in 2003, initially responded to the global AIDS epidemic by applying lessons learned in treating the disease in the United States to addressing the emergency abroad. As the program expanded, it evolved to support interventions increasingly tailored to local needs in countries receiving PEPFAR assistance. This global experience has created a knowledge base of how to provide HIV/AIDS prevention, care, and treatment services in low-resource settings. It underscored the importance of treatment adherence, family-centered care, and integration of HIV into broader health care delivery systems. Applying these lessons can help US policy makers address existing gaps in HIV care in the United States, where the availability of HIV treatment has at times masked the continued need for testing, early diagnosis, targeted prevention for key populations, and a solid array of social services for people living with HIV/AIDS and their families. This article identifies PEPFAR practices that merit further exploration for adoption in the United States, including strategies to increase adherence to drug treatment regimens and to ensure that HIV services are broadly integrated with other aspects of health care. PMID- 22778350 TI - The President's Emergency Plan for AIDS Relief: marshalling all tools at our disposal toward an AIDS-free generation. AB - For the first time in the thirty-year history of AIDS, scientific research and successful HIV programs have made an AIDS-free generation a realistic global ambition. The President's Emergency Plan for AIDS Relief (PEPFAR) laid the foundation for reaching this goal. This article reviews PEPFAR's efforts to date and highlights programs, such as those encouraging voluntary male circumcision, that have worked to reduce HIV transmission and improve health for people with HIV. It also identifies remaining challenges, such as continuing to lower the costs of programs per unit of service delivered. PEPFAR will continue to expand and share its understanding of what works, focus on evidence-based "combination prevention" strategies, and make investments that maximize the impact of each dollar spent. It will also support growing ownership by partner countries of HIV/AIDS programs in terms of both management and financing, which are keys to the long-term sustainability of those programs. The article closes with a call to marshal every scientific, public health, and political tool at our disposal to achieve an AIDS-free generation. PMID- 22778351 TI - Physician, researcher, and policy maker takes on HIV/AIDS. AB - From his days as a young physician in San Francisco to his current role as the US Global AIDS Coordinator, Eric Goosby has seen the damage done by HIV and has dedicated his career to lessening it. PMID- 22778352 TI - A room with a grim view: the 'ambient despair' that marks life in assisted living. AB - After entering an assisted living facility at age fifty-three because of young onset Parkinson's, an observer-advocate contemplates the dire need for long-term care reform. PMID- 22778353 TI - HIV/AIDS in African children: the Bristol-Myers Squibb Foundation and Baylor response. AB - In 2000, 1.4 million children were living with HIV/AIDS in sub-Saharan Africa, according to the Joint United Nations Programme on HIV/AIDS. Few of them were receiving lifesaving antiretroviral therapy because public health systems lacked the clinical infrastructure and trained health care workers to implement and disseminate high-quality care. Research has shown that without treatment, half of HIV-infected infants die by age two. From 2000 to 2011 the Bristol-Myers Squibb Foundation worked with the Baylor International Pediatric AIDS Initiative, governments in sub-Saharan Africa, and other funders to help ensure that children received needed treatment and care. The partnership led to the creation of seven Children's Clinical Centers for Excellence and the Pediatric AIDS Corps of physicians. The mortality rate for the 13,154 children receiving antiretroviral therapy at the centers was 3.35 deaths per 100 patient-years, which compares favorably with results of similar programs in Africa. The experience showed that strategic investments by foundations and others can have a positive impact on health service delivery and the training of health professionals to meet the specific needs of HIV-infected children for the short and long terms. PMID- 22778355 TI - The essence of palliative care. PMID- 22778356 TI - Living and dying well: Amy Berman leads by example. PMID- 22778357 TI - Walk the talk: living and dying in our own ways. PMID- 22778359 TI - The right therapy for prostate cancer. PMID- 22778361 TI - Medicare spending on home care. PMID- 22778363 TI - Don't delay implementation of ICD-10. PMID- 22778364 TI - Novel POLG1 mutations in a patient with adult-onset progressive external ophthalmoplegia and encephalopathy. AB - Mutations in POLG1 are an important cause of human mitochondrial disease. We describe a woman who presented with bilateral ptosis and external ophthalmoplegia at 64 years of age. Neurological examination revealed symptoms of diffuse encephalopathy. The symptoms were progressive and at 67 years she was severely cognitively impaired, had severe bilateral ptosis and complete external ophthalmoplegia. Frequent cytochrome c oxidase-negative fibres were detected in muscle. Electrophysiological examination revealed myopathic changes and axonal neuropathy. Standard laboratory tests were normal. Brain CT showed general, moderate cortical atrophy. Molecular analysis of muscle DNA revealed multiple mitochondrial DNA deletions. Sequencing of the entire POLG1 gene revealed two changes c.2993C>T (p.998S>L) and c.3550G>C (p.1184D>H). Both mutations are previously unreported and confirmed to be compound heterozygous. Late-onset progressive external ophthalmoplegia with severe encephalopathy is an unusual combination in patients with POLG1 mutations. POLG-associated disease should be considered in any patient with unexplained or unusual neurological features. PMID- 22778365 TI - An ectopic pregnancy under the liver. AB - Ectopic pregnancy is a common but potential life-threatening condition. The most common ectopic location is in the fallopian tube. Here we report a case of an ectopic pregnancy in a non-communicating fallopian tube placed under the liver. PMID- 22778366 TI - Enterovirus--a double act. AB - This case report describes twins presenting approximately 24 h apart both with enterovirus meningoencephalitis. The presenting symptoms are described along with laboratory results. Both had extremely high white cell counts in cerebrospinal fluid, which were predominantly lymphocytes. Clinical course and outcomes are described. There was a potential delay in diagnosis of the second twin given the pathology of the twin sibling and the symptoms presented. PMID- 22778367 TI - Fulminant hepatic failure in a patient with advanced extragonadal germ cell tumour. AB - Fulminant hepatic failure (FHF) in association with metastatic cancer, without evidence of liver metastases, has not been previously reported in the literature. This report concerns a case of FHF in a 36-year-old man with advanced germ cell tumour arising from an extragonadal (retroperitoneal) primary. Liver function and encephalopathy improved following chemotherapy, suggesting prompt diagnosis and treatment may have cured the patient. Following completion of chemotherapy, he developed spontaneous bacterial endocarditis, requiring aortic valve replacement, a rare complication of curative chemotherapy. At 44 months post completion of chemotherapy, he has regained his premorbid performance status and has returned to work. PMID- 22778368 TI - Salbutamol: beware of the paradox! AB - A 7-year-old known asthmatic presented with an acute severe asthma attack to the Accident and Emergency department. Following a poor response to salbutamol and ipratropium nebulisers, he was given intravenous salbutamol and aminophylline. Over the course of the following 3 h, there was improvement in his bronchospasm with decreasing oxygen requirement, however, his respiratory rate showed an upward trend. Serial blood gas estimations showed a worsening metabolic acidosis unresponsive to two fluid boluses of 20 ml/kg of normal saline. Lactate levels were subsequently measured and found to be high, accounting for the metabolic acidosis. High lactate levels were attributed to intravenous salbutamol. His blood gases and lactate level returned to normal within 3 h after stopping intravenous salbutamol. He was recommended on salbutamol nebulisers while still continuing on intravenous aminophylline. He continued to improve and was discharged home after 4 days. PMID- 22778369 TI - An unusual surgical site infection in a liver transplant recipient. AB - Mycobacterium abscessus is a rare cause of human infection and is difficult to diagnose unless it is suspected. A 45-year-old woman underwent deceased donor liver transplantation following which she developed non-healing surgical site infection, which did not resolve with routine antibiotics for 2 months. The scraping of the wound revealed M abscessus infection. Definitive identification of this species of mycobacterium was possible by its growth characteristics on culture and reverse line blot hybridisation assay. She was treated with clarithromycin and cotrimaxazole as per sensitivity and showed complete recovery from the infection within 6 weeks of starting the drugs, which were continued for 6 months. We believe that this is the first documented case of surgical site infection by M abscessus in a liver transplant recipient. PMID- 22778370 TI - Spontaneous regression of focal nodular hyperplasia: a pathological report. AB - Focal nodular hyperplasia (FNH) is a benign tumour of the liver, occurring in 0.6 3% of the general population. Most lesions are diagnosed incidentally. With the increasing use and improvement of diagnostic imaging, FNH is being observed more often. It has been shown, using radiological approaches, that most FNH remain stable, or even regress, over a long follow-up period. In addition, it is extremely rare that FNH were discovered in elderly. However, to our knowledge, there is no pathological report illustrating the regression of FNH. We report here a case showing the pathological changes occurring during the regression phase of FNH, with dense fibrous tissue mixed with arteries replacing hepatocytes nodules. PMID- 22778371 TI - The first case of Plasmodium ovale malaria from Bangladesh. AB - The authors report the first indigenous case of Plasmodium ovale infection from Bangladesh. The diagnosis was confirmed by PCR and sequence analysis. The patient had neither been outside of the country nor ever received blood transfusions. The authors concluded that there was evidence for a local transmission of P ovale malaria in Bangladesh. P ovale malaria should therefore always be considered a potential differential diagnosis in the indigenous population as well as travellers and migrants returning from South Asia, possibly up to years after their return. PMID- 22778372 TI - Cardiac lymphoma: ECG images pre-treatment and post-treatment. PMID- 22778373 TI - Distal pacemaker lead fracture: a rare entity. PMID- 22778374 TI - The hazards of honey: infantile botulism. AB - Infantile botulism is a rare cause of neuromuscular weakness resulting from ingestion of Clostridium botulinum-an anaerobic Gram-positive bacillus found universally in soil. The only definite food source known to cause infantile botulism is honey; previously, links to formula milk have been postulated but not definitely sourced. We present an interesting case report of a 2-month-old infant with this rare condition, including the diagnostic difficulties that ensued. A brief overview of the condition follows. This is the first case in the UK in which C botulinum was successfully isolated from both the patient and the suspected source-a jar of honey. The importance of food labelling as a public health message is highlighted. PMID- 22778375 TI - Kytococcus schroeteri prosthetic valve endocarditis. AB - We report the case of a 64-year-old male patient with a prosthetic aortic valve who presented with clinical features of endocarditis confirmed by transoesophageal echocardiography. His blood cultures were positive for a very rare and newly described organism-Kytococcus schroeteri. The patient underwent aortic valve replacement and a 6-week course of intravenous antibiotics. This is the fifth reported case of endocarditis associated with this organism. PMID- 22778376 TI - Fetoscopic imaging of isolated cleft lip. PMID- 22778378 TI - Spontaneous abscess of the lumbar spine presenting as subacute back pain. AB - A 52-year-old lady was admitted with back pain, fever and reduced sensation in her left leg. Soon after admission she developed acute urinary retention. She underwent urgent MRI of the spine which showed an epidural abscess compressing the thecal sac which was treated with neurosurgical decompression and intravenous/oral antibiotics. Cultures from theatre grew Staphylococcus aureus sensitive to flucloxacillin. After 12 weeks of intravenous/oral antibiotics, she was discharged without any neurological disability. PMID- 22778377 TI - Nocardiosis in a patient with rheumatoid arthritis treated with rituximab and a summary of reported cases. AB - Rituximab is a B-cell-depleting monoclonal anti-CD20 antibody. It is widely used in haematology and rheumatology. However, usage of rituximab in immunosupressed patient has been associated with various opportunistic infections. The authors reported a case of refractory rheumatoid arthritis treated with rituximab, which later presented with non-resolving pneumonia with pulmonary nodule. Percutaneous computer tomogram guided lung biopsy was arranged to confirm the suspicion of tuberculosis, but did not yield conclusive results. Later, she presented left chest abscess and underwent incision and drainage. The pus culture and sensitivity confirmed pulmonary nocardiosis with chest wall dissemination. She was treated with 2-week course of trimethoprim sulfamethoxazole and responded. The authors also reviewed published cases of nocardiosis post-rituximab. PMID- 22778379 TI - Delayed diagnosis of hypopituitarism following severe traumatic brain injury. AB - The following case illustrates a 10-year delay in the diagnosis of hypopituitarism after severe traumatic brain injury in a 22-year-old man crushed by a forklift truck. His symptoms of mood changes, headaches and sleep pattern disturbances were attributed to post traumatic brain injury syndrome resulting in a delay in diagnosing the underlying pathology. Following recurrent episodes of symptomatic hyponatraemia, hypopituitarism was diagnosed. When pituitary hormone replacement treatment was given, there was clinical and biochemical improvement. There is currently very limited evidence in the literature to routinely screen patients post traumatic brain injury for pituitary dysfunction. PMID- 22778380 TI - Malabsorption of antimycobacterial drugs as a cause of treatment failure in tuberculosis. AB - Malabsorption of oral antimycobacterial drugs is a rare cause of treatment failure in tuberculosis (TB). Several predisposing comorbidities have been recognised. HIV infection is the most important risk factor referred in the literature. There are few reports about antimycobacterial drugs malabsorption, particularly in the absence of predisposing comorbidities. The authors present a clinical case of oral treatment failure in TB due to malabsorption; however, what caused the failure remained unclear. Possible causes of malabsorption are discussed under various sections. Purpose of this case report is to point to this rare situation that can easily go unnoticed unless a very high level of suspicion is present. PMID- 22778382 TI - ADEA President's address. PMID- 22778383 TI - ADEA President-Elect's address. PMID- 22778384 TI - ADEA Executive Director's report. PMID- 22778385 TI - Proceedings of the 2012 ADEA House of Delegates. PMID- 22778387 TI - ADEA Mission Statement and Strategic Directions, 2011-14. PMID- 22778388 TI - Thymocytes may persist and differentiate without any input from bone marrow progenitors. AB - Thymus transplants can correct deficiencies of the thymus epithelium caused by the complete DiGeorge syndrome or FOXN1 mutations. However, thymus transplants were never used to correct T cell-intrinsic deficiencies because it is generally believed that thymocytes have short intrinsic lifespans. This notion is based on thymus transplantation experiments where it was shown that thymus-resident cells were rapidly replaced by progenitors originating in the bone marrow. In contrast, here we show that neonatal thymi transplanted into interleukin 7 receptor deficient hosts harbor populations with extensive capacity to self-renew, and maintain continuous thymocyte generation and export. These thymus transplants reconstitute the full diversity of peripheral T cell repertoires one month after surgery, which is the earliest time point studied. Moreover, transplantation experiments performed across major histocompatibility barriers show that allogeneic transplanted thymi are not rejected, and allogeneic cells do not induce graft-versus-host disease; transplants induced partial or total protection to infection. These results challenge the current dogma that thymocytes cannot self-renew, and indicate a potential use of neonatal thymus transplants to correct T cell-intrinsic deficiencies. Finally, as found with mature T cells, they show that thymocyte survival is determined by the competition between incoming progenitors and resident cells. PMID- 22778389 TI - Thymus-autonomous T cell development in the absence of progenitor import. AB - Thymus function is thought to depend on a steady supply of T cell progenitors from the bone marrow. The notion that the thymus lacks progenitors with self renewal capacity is based on thymus transplantation experiments in which host derived thymocytes replaced thymus-resident cells within 4 wk. Thymus grafting into T cell-deficient mice resulted in a wave of T cell export from the thymus, followed by colonization of the thymus by host-derived progenitors, and cessation of T cell development. Compound Rag2(-/-)gamma(c)(-/-)Kit(W/Wv) mutants lack competitive hematopoietic stem cells (HSCs) and are devoid of T cell progenitors. In this study, using this strain as recipients for wild-type thymus grafts, we noticed thymus-autonomous T cell development lasting several months. However, we found no evidence for export of donor HSCs from thymus to bone marrow. A diverse T cell antigen receptor repertoire in progenitor-deprived thymus grafts implied that many thymocytes were capable of self-renewal. Although the process was most efficient in Rag2(-/-)gamma(c)(-/-)Kit(W/Wv) hosts, gamma(c)-mediated signals alone played a key role in the competition between thymus-resident and bone marrow-derived progenitors. Hence, the turnover of each generation of thymocytes is not only based on short life span but is also driven via expulsion of resident thymocytes by fresh progenitors entering the thymus. PMID- 22778390 TI - A specific role for TLR1 in protective T(H)17 immunity during mucosal infection. AB - The balance between regulatory and inflammatory immune responses is critical to maintain intestinal homeostasis. Furthermore, the nature of the inflammatory response needs to be tailored to the tissue to provide proper protective immunity while preserving host integrity. TLR2 (Toll-like receptor 2) is a unique TLR in that it has been shown to promote regulatory and inflammatory T cell responses. Using Yersinia enterocolitica, we show that oral infection promotes T(H)17 immunity, whereas systemic infection promotes T(H)1 immunity. Furthermore, induction of T(H)17 immunity during oral infection is dependent on TLR1 and results from the combinatorial effect of TLR2/TLR1-induced IL-6 and IL-23 and the presence of TGF-beta in the intestinal environment. Interestingly, TLR2/TLR1 was not involved in T(H)1 immune responses during systemic infection, whereas the TLR2/TLR6 receptor complex induced IL-10(+) regulatory T cell responses during both systemic and oral infections. Our results reveal that the route of infection is central in determining which pathways provide protective immunity. Furthermore, they also demonstrate that TLR2 has dual immune functions in the gut and identify TLR1 as a critical innate receptor for protective intestinal T(H)17 immunity. PMID- 22778391 TI - Attenuation of acute graft-versus-host disease in the absence of the transcription factor RORgammat. AB - Graft-versus-host disease (GVHD) remains the most significant complication after allogeneic stem cell transplantation. Previously, acute GVHD had been considered to be mediated predominantly by Th1-polarized T cells. Recently, investigators have identified a second proinflammatory lineage of T cells termed Th17 that is critically dependent on the transcription factor retinoic acid-related orphan receptor (ROR)gammat. In this study, we have evaluated the role of Th17 cells in murine acute GVHD by infusing donor T cells lacking RORC and as a consequence the isoform RORgammat. Recipients given donor CD4(+) and CD8(+) T cells lacking RORC had significantly attenuated acute GVHD and markedly decreased tissue pathology in the colon, liver, and lung. Using a clinically relevant haploidentical murine transplantation model, we showed that RORC(-/-) CD4(+) T cells alone diminished the severity and lethality of acute GVHD. This was not found when CD4(+) T cells from RORC(-/-) mice were given to completely mismatched BALB/c mice, and it was correlated with absolute differences in the generation of TNF in the colon after transplant. Thus, CD4(+) T cell expression of RORC is important in the pathogenesis of acute GVHD. PMID- 22778392 TI - Spontaneous autoimmunity in the absence of IL-2 is driven by uncontrolled dendritic cells. AB - BALB/c IL-2-deficient (IL-2-KO) mice develop systemic autoimmunity, dying within 3 to 5 wk from complications of autoimmune hemolytic anemia. Disease in these mice is Th1 mediated, and IFN-gamma production is required for early autoimmunity. In this study, we show that dendritic cells (DCs) are required for optimal IFN-gamma production by T cells in the IL-2-KO mouse. Disease is marked by DC accumulation, activation, and elevated production of Th1-inducing cytokines. IL-2-KO DCs induce heightened proliferation and cytokine production by naive T cells compared with wild-type DCs. The depletion of either conventional or plasmacytoid DCs significantly prolongs the survival of IL-2-KO mice, demonstrating that DCs contribute to the progression of autoimmunity. Elimination of Th1-inducing cytokine signals (type 1 IFN and IL-12) reduces RBC-specific Ab production and augments survival, indicating that cytokines derived from both plasmacytoid DCs and conventional DCs contribute to disease severity. DC activation likely precedes T cell activation because DCs are functionally activated even in an environment lacking overt T cell activation. These data indicate that both conventional and plasmacytoid DCs are critical regulators in the development of this systemic Ab-mediated autoimmune disease, in large part through the production of IL-12 and type 1 IFNs. PMID- 22778393 TI - GPR105 ablation prevents inflammation and improves insulin sensitivity in mice with diet-induced obesity. AB - GPR105, a G protein-coupled receptor for UDP-glucose, is highly expressed in several human tissues and participates in the innate immune response. Because inflammation has been implicated as a key initial trigger for type 2 diabetes, we hypothesized that GPR105 (official gene name: P2RY14) might play a role in the initiation of inflammation and insulin resistance in obesity. To this end, we investigated glucose metabolism in GPR105 knockout (KO) and wild-type (WT) mice fed a high-fat diet (HFD). We also examined whether GPR105 regulates macrophage recruitment to liver or adipose tissues by in vivo monocyte tracking and in vitro chemotaxis experiments, followed by transplantation of bone marrow from either KO or WT donors to WT recipients. Our data show that genetic deletion of GPR105 confers protection against HFD-induced insulin resistance, with reduced macrophage infiltration and inflammation in liver, and increased insulin stimulated Akt phosphorylation in liver, muscle, and adipose tissue. By tracking monocytes from either KO or WT donors, we found that fewer KO monocytes were recruited to the liver of WT recipients. Furthermore, we observed that uridine 5 diphosphoglucose enhanced the in vitro migration of bone marrow-derived macrophages from WT but not KO mice, and that plasma uridine 5-diphosphoglucose levels were significantly higher in obese versus lean mice. Finally, we confirmed that insulin sensitivity improved in HFD mice with a myeloid cell-specific deletion of GPR105. These studies indicate that GPR105 ablation mitigates HFD induced insulin resistance by inhibiting macrophage recruitment and tissue inflammation. Hence GPR105 provides a novel link between innate immunity and metabolism. PMID- 22778394 TI - IFN-gamma receptor-deficient donor T cells mediate protection from graft-versus host disease and preserve graft-versus-tumor responses after allogeneic bone marrow transplantation. AB - Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. It has been previously reported that lung GVHD severity directly correlates with the expansion of donor Th17 cells in the absence of IFN gamma. However, the consequence of Th17-associated lung GVHD in the presence of IFN-gamma has not been well characterized. In the current study, T cells from IFN gamma receptor knockout (IFN-gammaR(-/-)) mice, capable of producing IFN-gamma but unable to signal in response to IFN-gamma, have been used to elucidate further the role of IFN-gamma in GVHD. We found the transfer of donor T cells from either IFN-gammaR(-/-) or IFN-gamma knockout (IFN-gamma(-/-)) mice resulted in significant increases in donor Th17 cells in the lung. Marked increases in IL 4-producing Th2 cells infiltrating the lungs were also observed in the mice of donor IFN-gammaR(-/-) T cells. Notably, despite the presence of these cells, these mice did not show the severe immune-mediated histopathological lung injury observed in mice receiving donor IFN-gamma(-/-) T cells. Increases in lung GVHD did occur in mice with donor IFN-gammaR(-/-) T cells when treated in vivo with anti-IFN-gamma demonstrating that the cytokine has a protective role on host tissues in GVHD. A survival benefit from acute GVHD was also observed using donor cells from IFN-gammaR(-/-) T cells compared with control donors. Importantly, tumor-bearing mice receiving IFN-gammaR(-/-) T cells versus wild-type donor T cells displayed similar graft-versus-tumor (GVT) effects. These results demonstrate the critical role of IFN-gamma on host tissues and cell effector functions in GVHD/GVT. PMID- 22778395 TI - The prolyl hydroxylase PHD3 identifies proinflammatory macrophages and its expression is regulated by activin A. AB - Modulation of macrophage polarization underlies the onset and resolution of inflammatory processes, with polarization-specific molecules being actively sought as potential diagnostic and therapeutic tools. Based on their cytokine profile upon exposure to pathogenic stimuli, human monocyte-derived macrophages generated in the presence of GM-CSF or M-CSF are considered as proinflammatory (M1) or anti-inflammatory (M2) macrophages, respectively. We report in this study that the prolyl hydroxylase PHD3-encoding EGLN3 gene is specifically expressed by in vitro-generated proinflammatory M1(GM-CSF) human macrophages at the mRNA and protein level. Immunohistochemical analysis revealed the expression of PHD3 in CD163(+) lung macrophages under basal homeostatic conditions, whereas PHD3(+) macrophages were abundantly found in tissues undergoing inflammatory responses (e.g., Crohn's disease and ulcerative colitis) and in tumors. In the case of melanoma, PHD3 expression marked a subset of tumor-associated macrophages that exhibit a weak (e.g., CD163) or absent (e.g., FOLR2) expression of typical M2 polarization markers. EGLN3 gene expression in proinflammatory M1(GM-CSF) macrophages was found to be activin A dependent and could be prevented in the presence of an anti-activin A-blocking Ab or inhibitors of activin receptor-like kinase receptors. Moreover, EGLN3 gene expression was upregulated in response to hypoxia only in M2(M-CSF) macrophages, and the hypoxia-mediated upregulation of EGLN3 expression was significantly impaired by activin A neutralization. These results indicate that EGLN3 gene expression in macrophages is dependent on activin A both under basal and hypoxic conditions and that the expression of the EGLN3-encoded PHD3 prolyl hydroxylase identifies proinflammatory macrophages in vivo and in vitro. PMID- 22778396 TI - Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis. AB - Tuberculosis, one of the leading causes of death worldwide, stimulates inflammatory responses with beneficial and pathologic consequences. The regulation and nature of an optimal inflammatory response to Mycobacterium tuberculosis remains poorly understood in humans. Insight into mechanisms of negative regulation of the TLR-mediated innate immune response to M. tuberculosis could provide significant breakthroughs in the design of new vaccines and drugs. We hypothesized that TOLLIP and its common variants negatively regulate TLR signaling in human monocytes and are associated with susceptibility to tuberculosis. Using short hairpin RNA knockdown of TOLLIP in peripheral blood human monocytes, we found that TOLLIP suppresses TNF and IL-6 production after stimulation with TLR2 and TLR4 ligands. In contrast, secretion of the anti inflammatory cytokine IL-10 was induced by TOLLIP. We also discovered two common polymorphisms that are associated with either decreased levels of mRNA expression (rs3750920) or increased IL-6 production (rs5743899) in a sample of 56 healthy volunteers. Furthermore, in a case-population study in Vietnam with 760 cord blood samples and 671 TB case patients, we found that SNPs rs3750920 and rs5743899 were associated with susceptibility to tuberculosis (p = 7.03 * 10(-16) and 6.97 * 10(-7), respectively). These data demonstrate that TOLLIP has an anti inflammatory effect on TLR signaling in humans and that TOLLIP deficiency is associated with an increased risk of tuberculosis. To our knowledge, these data also show the first associations of TOLLIP polymorphisms with any infectious disease. These data also implicate an unexpected mechanism of negative regulation of TLR signaling in human tuberculosis pathogenesis. PMID- 22778397 TI - Structural and energetic basis of ALS-causing mutations in the atypical proline tyrosine nuclear localization signal of the Fused in Sarcoma protein (FUS). AB - Mutations in the proline/tyrosine-nuclear localization signal (PY-NLS) of the Fused in Sarcoma protein (FUS) cause amyotrophic lateral sclerosis (ALS). Here we report the crystal structure of the FUS PY-NLS bound to its nuclear import receptor Karyopherinbeta2 (Kapbeta2; also known as Transportin). The FUS PY-NLS occupies the structurally invariant C-terminal arch of Kapbeta2, tracing a path similar to that of other characterized PY-NLSs. Unlike other PY-NLSs, which generally bind Kapbeta2 in fully extended conformations, the FUS peptide is atypical as its central portion forms a 2.5-turn alpha-helix. The Kapbeta2 binding epitopes of the FUS PY-NLS consist of an N-terminal PGKM hydrophobic motif, a central arginine-rich alpha-helix, and a C-terminal PY motif. ALS mutations are found almost exclusively within these epitopes. Each ALS mutation site makes multiple contacts with Kapbeta2 and mutations of these residues decrease binding affinities for Kapbeta2 (K(D) for wild-type FUS PY-NLS is 9.5 nM) up to ninefold. Thermodynamic analyses of ALS mutations in the FUS PY-NLS show that the weakening of FUS-Kapbeta2 binding affinity, the degree of cytoplasmic mislocalization, and ALS disease severity are correlated. PMID- 22778398 TI - Plasminogen activator inhibitor 1--insulin-like growth factor binding protein 3 cascade regulates stress-induced senescence. AB - Cellular senescence is widely believed to play a key role in tumor suppression, but the molecular pathways that regulate senescence are only incompletely understood. By using a secretome proteomics approach, we identified insulin-like growth factor binding protein 3 (IGFBP3) as a secreted mediator of breast cancer senescence upon chemotherapeutic drug treatment. The senescence-inducing activity of IGFBP3 is inhibited by tissue-type plasminogen activator-mediated proteolysis, which is counteracted by plasminogen activator inhibitor 1 (PAI-1), another secreted mediator of senescence. We demonstrate that IGFBP3 is a critical downstream target of PAI-1-induced senescence. These results suggest a role for an extracellular cascade of secreted proteins in the regulation of cellular senescence. PMID- 22778399 TI - Inactivation of a single gene enables microaerobic growth of the obligate anaerobe Bacteroides fragilis. AB - Bacteroides fragilis can replicate in atmospheres containing <=0.05% oxygen, but higher concentrations arrest growth by an unknown mechanism. Here we show that inactivation of a single gene, oxe (i.e., oxygen enabled) in B. fragilis allows for growth in concentrations as high as 2% oxygen while increasing the tolerance of this organism to room air. Known components of the oxidative stress response including the ahpC, kat, batA-E, and tpx genes were not individually important for microaerobic growth. However, a Deltaoxe strain scavenged H(2)O(2) at a faster rate than WT, indicating that reactive oxygen species may play a critical role in limiting growth of this organism to low-oxygen environments. Clinical isolates of B. fragilis displayed a greater capacity for growth under microaerobic conditions than fecal isolates, with some encoding polymorphisms in oxe. Additionally, isolation of oxygen-enabled mutants of Bacteroides thetaiotaomicron suggests that Oxe may mediate growth arrest of other anaerobes in oxygenated environments. PMID- 22778400 TI - Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines. AB - Chronic sleep deprivation perturbs the circadian clock and increases susceptibility to diseases such as diabetes, obesity, and cancer. Increased inflammation is one of the common underlying mechanisms of these diseases, thus raising a hypothesis that circadian-oscillator components may regulate immune response. Here we show that absence of the core clock component protein cryptochrome (CRY) leads to constitutive elevation of proinflammatory cytokines in a cell-autonomous manner. We observed a constitutive NF-kappaB and protein kinase A (PKA) signaling activation in Cry1(-/-);Cry2(-/-) cells. We further demonstrate that increased phosphorylation of p65 at S276 residue in Cry1(-/ );Cry2(-/-) cells is due to increased PKA signaling activity, likely induced by a significantly high basal level of cAMP, which we detected in these cells. In addition, we report that CRY1 binds to adenylyl cyclase and limits cAMP production. Based on these data, we propose that absence of CRY protein(s) might release its (their) inhibition on cAMP production, resulting in elevated cAMP and increased PKA activation, subsequently leading to NF-kappaB activation through phosphorylation of p65 at S276. These results offer a mechanistic framework for understanding the link between circadian rhythm disruption and increased susceptibility to chronic inflammatory diseases. PMID- 22778401 TI - Brain dopamine and serotonin differ in regulation and its consequences. AB - Dopamine and serotonin (5-hydroxytryptamine or 5-HT) are neurotransmitters that are implicated in many psychological disorders. Although dopamine transmission in the brain has been studied extensively in vivo with fast scan cyclic voltammetry, detection of 5-HT using in vivo voltammetric methods has only recently been established. In this work we use two carbon-fiber microelectrodes to simultaneously measure dopamine release in the nucleus accumbens and 5-HT release in the substantia nigra pars reticulata, using a common stimulation in a single rat. We find that 5-HT release is profoundly restricted in comparison with dopamine release despite comparable tissue content levels. Using physiological and pharmacological analysis, we find that 5-HT transmission is mostly sensitive to uptake and metabolic degradation mechanisms. In contrast, dopamine transmission is constrained by synthesis and repackaging. Finally, we show that disruption of serotonergic regulatory mechanisms by simultaneous inhibition of uptake and metabolic degradation can have severe physiological consequences that mimic serotonin syndrome. PMID- 22778402 TI - Chemotactic signaling via carbohydrate phosphotransferase systems in Escherichia coli. AB - Chemotaxis allows bacteria to follow gradients of nutrients, environmental stimuli, and signaling molecules, optimizing bacterial growth and survival. Escherichia coli has long served as a model of bacterial chemotaxis, and the signal processing by the core of its chemotaxis pathway is well understood. However, most of the research so far has focused on one branch of chemotactic signaling, in which ligands bind to periplasmic sensory domains of transmembrane chemoreceptors and induce a conformational change that is transduced across the membrane to regulate activity of the receptor-associated kinase CheA. Here we quantitatively characterize another, receptor-independent branch of chemotactic signaling that is linked to the sugar uptake through a large family of phosphotransferase systems (PTSs). Using in vivo characterization of intracellular signaling and protein interactions, we demonstrate that signals from cytoplasmic PTS components are transmitted directly to the sensory complexes formed by chemoreceptors, CheA and an adapter protein CheW. We further conclude that despite different modes of sensing, the PTS- and receptor-mediated signals have similar regulatory effects on the conformation of the sensory complexes. As a consequence, both types of signals become integrated and undergo common downstream processing including methylation-dependent adaptation. We propose that such mode of signaling is essential for efficient chemotaxis to PTS substrates and may be common to most bacteria. PMID- 22778403 TI - Inositol hexakisphosphate suppresses excitatory neurotransmission via synaptotagmin-1 C2B domain in the hippocampal neuron. AB - Inositol hexakisphosphate (InsP(6)) levels rise and fall with neuronal excitation and silence, respectively, in the hippocampus, suggesting potential signaling functions of this inositol polyphosphate in hippocampal neurons. We now demonstrate that intracellular application of InsP(6) caused a concentration dependent inhibition of autaptic excitatory postsynaptic currents (EPSCs) in cultured hippocampal neurons. The treatment did not alter the size and replenishment rate of the readily releasable pool in autaptic neurons. Intracellular exposure to InsP(6) did not affect spontaneous EPSCs or excitatory amino acid-activated currents in neurons lacking autapses. The InsP(6)-induced inhibition of autaptic EPSCs was effectively abolished by coapplication of an antibody to synaptotagmin-1 C2B domain. Importantly, preabsorption of the antibody with a GST-WT synaptotagmin-1 C2B domain fragment but not with a GST mutant synaptotagmin-1 C2B domain fragment that poorly reacted with the antibody impaired the activity of the antibody on the InsP(6)-induced inhibition of autaptic EPSCs. Furthermore, K(+) depolarization significantly elevated endogenous levels of InsP(6) and occluded the inhibition of autaptic EPSCs by exogenous InsP(6). These data reveal that InsP(6) suppresses excitatory neurotransmission via inhibition of the presynaptic synaptotagmin-1 C2B domain mediated fusion via an interaction with the synaptotagmin Ca(2+)-binding sites rather than via interference with presynaptic Ca(2+) levels, synaptic vesicle trafficking, or inactivation of postsynaptic ionotropic glutamate receptors. Therefore, elevated InsP(6) in activated neurons serves as a unique negative feedback signal to control hippocampal excitatory neurotransmission. PMID- 22778404 TI - Sialin (SLC17A5) functions as a nitrate transporter in the plasma membrane. AB - In vivo recycling of nitrate (NO(3)(-)) and nitrite (NO(2)(-)) is an important alternative pathway for the generation of nitric oxide (NO) and maintenance of systemic nitrate-nitrite-NO balance. More than 25% of the circulating NO(3)(-) is actively removed and secreted by salivary glands. Oral commensal bacteria convert salivary NO(3)(-) to NO(2)(-), which enters circulation and leads to NO generation. The transporters for NO(3)(-) in salivary glands have not yet been identified. Here we report that sialin (SLC17A5), mutations in which cause Salla disease and infantile sialic acid storage disorder (ISSD), functions as an electrogenic 2NO(3)(-)/H(+) cotransporter in the plasma membrane of salivary gland acinar cells. We have identified an extracellular pH-dependent anion current that is carried by NO(3)(-) or sialic acid (SA), but not by Br(-), and is accompanied by intracellular acidification. Both responses were reduced by knockdown of sialin expression and increased by the plasma membrane-targeted sialin mutant (L22A-L23A). Fibroblasts from patients with ISSD displayed reduced SA- and NO(3)(-)-induced currents compared with healthy controls. Furthermore, expression of disease-associated sialin mutants in fibroblasts and salivary gland cells suppressed the H(+)-dependent NO(3)(-) conductance. Importantly, adenovirus dependent expression of the sialinH183R mutant in vivo in pig salivary glands decreased NO(3)(-) secretion in saliva after intake of a NO(3)(-)-rich diet. Taken together, these data demonstrate that sialin mediates nitrate influx into salivary gland and other cell types. We suggest that the 2NO(3)(-)/H(+) transport function of sialin in salivary glands can contribute significantly to clearance of serum nitrate, as well as nitrate recycling and physiological nitrite-NO homeostasis. PMID- 22778406 TI - A fungal gene reinforces Mendel's laws by counteracting genetic cheating. PMID- 22778405 TI - Insights into salt tolerance from the genome of Thellungiella salsuginea. AB - Thellungiella salsuginea, a close relative of Arabidopsis, represents an extremophile model for abiotic stress tolerance studies. We present the draft sequence of the T. salsuginea genome, assembled based on ~134-fold coverage to seven chromosomes with a coding capacity of at least 28,457 genes. This genome provides resources and evidence about the nature of defense mechanisms constituting the genetic basis underlying plant abiotic stress tolerance. Comparative genomics and experimental analyses identified genes related to cation transport, abscisic acid signaling, and wax production prominent in T. salsuginea as possible contributors to its success in stressful environments. PMID- 22778407 TI - C-fiber activity-dependent maturation of glycinergic inhibition in the spinal dorsal horn of the postnatal rat. AB - Sensory circuits are shaped by experience in early postnatal life and in many brain areas late maturation of inhibition drives activity-dependent development. In the newborn spinal dorsal horn, activity is dominated by inputs from low threshold A fibers, whereas nociceptive C-fiber inputs mature gradually over the first postnatal weeks. How this changing afferent input influences the maturation of dorsal horn inhibition is not known. We show an absence of functional glycinergic inhibition in newborn dorsal horn circuits: Dorsal horn receptive fields and afferent-evoked excitation are initially facilitated by glycinergic activity due, at least in part, to glycinergic disinhibition of GAD67 cells. Glycinergic inhibitory control emerges in the second postnatal week, coinciding with an expression switch from neonatal alpha(2) homomeric to predominantly mature alpha(1)/beta glycine receptors (GlyRs). We further show that the onset of glycinergic inhibition depends upon the maturation of C-fiber inputs to the dorsal horn: selective block of afferent C fibers in postnatal week 2, using perisciatic injections of the cationic anesthetic QX-314, lidocaine, and capsaicin, delays the maturation of both GlyR subunits and glycinergic inhibition, maintaining dorsal neurons in a neonatal state, where tactile responses are facilitated, rather than inhibited, by glycinergic network activity. Thus, glycine may serve to facilitate tactile A-fiber-mediated information and enhance activity-dependent synaptic strengthening in the immature dorsal horn. This period ceases in the second postnatal week with the maturation of C-fiber spinal input, which triggers postsynaptic changes leading to glycinergic inhibition and only then is balanced excitation and inhibition achieved in dorsal horn sensory circuits. PMID- 22778408 TI - Resetting capacity limitations revealed by long-lasting elimination of attentional blink through training. AB - As with other cognitive phenomena that are based upon the capacity limitations of visual processing, it is thought that attentional blink (AB) cannot be eliminated, even after extensive training. We report in this paper that just 1 h of specific attentional training can completely eliminate AB, and that this effect is robust enough to persist for a few months after training. Results of subsequent behavioral and functional magnetic resonance imaging (fMRI) experiments indicate that this learning effect is associated with improvements in temporal resolution, which are mainly due to processing in the prefrontal areas. Contrary to prior wisdom, we conclude that capacity limitations can be overcome by short-term training. PMID- 22778409 TI - Up-regulation of the mitotic checkpoint component Mad1 causes chromosomal instability and resistance to microtubule poisons. AB - The mitotic checkpoint is the major cell cycle checkpoint acting during mitosis to prevent aneuploidy and chromosomal instability, which are hallmarks of tumor cells. Reduced expression of the mitotic checkpoint component Mad1 causes aneuploidy and promotes tumors in mice [Iwanaga Y, et al. (2007) Cancer Res 67:160-166]. However, the prevalence and consequences of Mad1 overexpression are currently unclear. Here we show that Mad1 is frequently overexpressed in human cancers and that Mad1 up-regulation is a marker of poor prognosis. Overexpression of Mad1 causes aneuploidy and chromosomal instability through weakening mitotic checkpoint signaling caused by mislocalization of the Mad1 binding partner Mad2. Cells overexpressing Mad1 are resistant to microtubule poisons, including currently used chemotherapeutic agents. These results suggest that levels of Mad1 must be tightly regulated to prevent aneuploidy and transformation and that Mad1 up-regulation may promote tumors and cause resistance to current therapies. PMID- 22778411 TI - Monkeys have a limited form of short-term memory in audition. AB - A stimulus trace may be temporarily retained either actively [i.e., in working memory (WM)] or by the weaker mnemonic process we will call passive short-term memory, in which a given stimulus trace is highly susceptible to "overwriting" by a subsequent stimulus. It has been suggested that WM is the more robust process because it exploits long-term memory (i.e., a current stimulus activates a stored representation of that stimulus, which can then be actively maintained). Recent studies have suggested that monkeys may be unable to store acoustic signals in long-term memory, raising the possibility that they may therefore also lack auditory WM. To explore this possibility, we tested rhesus monkeys on a serial delayed match-to-sample (DMS) task using a small set of sounds presented with ~1 s interstimulus delays. Performance was accurate whenever a match or a nonmatch stimulus followed the sample directly, but it fell precipitously if a single nonmatch stimulus intervened between sample and match. The steep drop in accuracy was found to be due not to passive decay of the sample's trace, but to retroactive interference from the intervening nonmatch stimulus. This "overwriting" effect was far greater than that observed previously in serial DMS with visual stimuli. The results, which accord with the notion that WM relies on long-term memory, indicate that monkeys perform serial DMS in audition remarkably poorly and that whatever success they had on this task depended largely, if not entirely, on the retention of stimulus traces in the passive form of short-term memory. PMID- 22778410 TI - Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity. AB - Depression is a debilitating mental illness and is often comorbid with metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte-derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, "anhedonia," and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic pituitary-adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressant-like behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders. PMID- 22778412 TI - Interleukin-1R3 mediates interleukin-1-induced potassium current increase through fast activation of Akt kinase. AB - Inflammatory cytokine interleukin-1 (IL-1) performs multiple functions in the central nervous system. The type 1 IL-1 receptor (IL-1R1) and the IL-1 receptor accessory protein (IL-1RAcP) form a functional IL-1 receptor complex that is thought to mediate most, if not all, IL-1-induced effects. Several recent studies, however, suggest the existence of a heretofore-unidentified receptor for IL-1. In this study, we report that the IL-1R1 gene contains an internal promoter that drives the transcription of a shortened IL-1R1 mRNA. This mRNA is the template for a unique IL-1R protein that is identical to IL-1R1 at the C terminus, but with a shorter extracellular domain at the N terminus. We have termed this molecule IL-1R3. The mRNA and protein for IL-1R3 are expressed in normal and two strains of commercially available IL-1R1 knockout mice. Western blot analysis shows IL-1R3 is preferentially expressed in neural tissues. Furthermore, IL-1beta binds specifically to IL-1R3 when it is complexed with the newly discovered alternative IL-1 receptor accessory protein, IL-1RAcPb. Stimulation of neurons expressing both IL-1R3 and IL-1RAcPb with IL-1beta causes fast activation of the Akt kinase, which leads to an increase in voltage-gated potassium current. These results demonstrate that IL-1R3/IL-1RAcPb complex mediates a unique subset of IL-1 activity that accounts for many previously unexplained IL-1 effects in the central nervous system. PMID- 22778413 TI - A Plasmodium-encoded cytokine suppresses T-cell immunity during malaria. AB - The inability to acquire protective immunity against Plasmodia is the chief obstacle to malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection. Malaria is characterized by a highly inflammatory cytokine milieu, and the lack of effective protection against infection suggests that memory T cells are not adequately formed or maintained. Using a genetically targeted strain of Plasmodium berghei, we observed that the Plasmodium ortholog of macrophage migration inhibitory factor enhanced inflammatory cytokine production and also induced antigen-experienced CD4 T cells to develop into short-lived effector cells rather than memory precursor cells. The short-lived effector CD4 T cells were more susceptible to Bcl-2-associated apoptosis, resulting in decreased CD4 T-cell recall responses against challenge infections. These findings indicate that Plasmodia actively interfere with the development of immunological memory and may account for the evolutionary conservation of parasite macrophage migration inhibitory factor orthologs. PMID- 22778414 TI - Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries. AB - It has been generally accepted for more than half a century that, in most mammalian species, oocytes cannot renew themselves in postnatal or adult life, and that the number of oocytes is already fixed in fetal or neonatal ovaries. This assumption, however, has been challenged over the past decade. In this study, we have taken an endogenous genetic approach to this question and generated a multiple fluorescent Rosa26(rbw/+);Ddx4-Cre germline reporter mouse model for in vivo and in vitro tracing of the development of female germline cell lineage. Through live cell imaging and de novo folliculogenesis experiments, we show that the Ddx4-expressing cells from postnatal mouse ovaries did not enter mitosis, nor did they contribute to oocytes during de novo folliculogenesis. Our results provide evidence that supports the traditional view that no postnatal follicular renewal occurs in mammals, and no mitotically active Ddx4-expressing female germline progenitors exist in postnatal mouse ovaries. PMID- 22778415 TI - Antisense RNA that affects Rhodopseudomonas palustris quorum-sensing signal receptor expression. AB - Quorum sensing in the bacterium Rhodopseudomonas palustris involves the RpaI signal synthase, which produces p-coumaroyl-homoserine lactone (pC-HSL) and RpaR, which is a pC-HSL-dependent transcriptional activator. There is also an antisense rpaR transcript (asrpaR) of unknown function. Recent RNAseq studies have revealed that bacterial antisense RNAs are abundant, but little is known about the function of these molecules. Because asrpaR expression is quorum sensing dependent, we sought to characterize its production and function. We show that asrpaR is approximately 300-600 bases and is produced in response to pC-HSL and RpaR. There is an RpaR-binding site centered 51.5 bp from the mapped asrpaR transcript start site. We show that asrpaR overexpression reduces RpaR levels, rpaI expression, and pC-HSL production. We also generated an asrpaR mutant, which shows elevated RpaR levels, and elevated rpaI expression. Thus, asrpaR inhibits rpaR translation, and this inhibition results in suppression of RpaR-dependent rpaI expression and, thus, pC-HSL production. The R. palustris asrpaR represents an antisense RNA for which an activity can be measured and for which a distinct regulatory circuit related to a function is elucidated. It also represents yet another subtle regulatory layer for acyl-homoserine lactone quorum-sensing signal responsive transcription factors. PMID- 22778416 TI - Characterization of two neuronal subclasses through constellation pharmacology. AB - Different types of neurons diverge in function because they express their own unique set or constellation of signaling molecules, including receptors and ion channels that work in concert. We describe an approach to identify functionally divergent neurons within a large, heterogeneous neuronal population while simultaneously investigating specific isoforms of signaling molecules expressed in each. In this study we characterized two subclasses of menthol-sensitive neurons from cultures of dissociated mouse dorsal-root ganglia. Although these neurons represent a small fraction of the dorsal-root ganglia neuronal population, we were able to identify them and investigate the cell-specific constellations of ion channels and receptors functionally expressed in each subclass, using a panel of selective pharmacological tools. Differences were found in the functional expression of ATP receptors, TRPA1 channels, voltage gated calcium-, potassium-, and sodium channels, and responses to physiologically relevant cold temperatures. Furthermore, the cell-specific responses to various stimuli could be altered through pharmacological interventions targeted to the cell-specific constellation of ion channels expressed in each menthol-sensitive subclass. In fact, the normal responses to cold temperature could be reversed in the two neuronal subclasses by the coapplication of the appropriate combination of pharmacological agents. This result suggests that the functionally integrated constellation of signaling molecules in a particular type of cell is a more appropriate target for effective pharmacological intervention than a single signaling molecule. This shift from molecular to cellular targets has important implications for basic research and drug discovery. We refer to this paradigm as "constellation pharmacology." PMID- 22778417 TI - Sushi domains confer distinct trafficking profiles on GABAB receptors. AB - GABA(B) receptors mediate slow inhibitory neurotransmission in the brain and feature during excitatory synaptic plasticity, as well as various neurological conditions. These receptors are obligate heterodimers composed of GABA(B)R1 and R2 subunits. The two predominant R1 isoforms differ by the presence of two complement control protein modules or Sushi domains (SDs) in the N terminus of R1a. By using live imaging, with an alpha-bungarotoxin-binding site (BBS) and fluorophore-linked bungarotoxin, we studied how R2 stabilizes R1b subunits at the cell surface. Heterodimerization with R2 reduced the rate of internalization of R1b, compared with R1b homomers. However, R1aR2 heteromers exhibited increased cell surface stability compared with R1bR2 receptors in hippocampal neurons, suggesting that for receptors containing the R1a subunit, the SDs play an additional role in the surface stability of GABA(B) receptors. Both SDs were necessary to increase the stability of R1aR2 because single deletions caused the receptors to be internalized at the same rate and extent as R1bR2 receptors. Consistent with these findings, a chimera formed from the metabotropic glutamate receptor (mGluR)2 and the SDs from R1a increased the surface stability of mGluR2. These results suggest a role for SDs in stabilizing cell surface receptors that could impart different pre- and postsynaptic trafficking itineraries on GABA(B) receptors, thereby contributing to their physiological and pathological roles. PMID- 22778418 TI - Maternally recruited Aurora C kinase is more stable than Aurora B to support mouse oocyte maturation and early development. AB - Aurora kinases are highly conserved, essential regulators of cell division. Two Aurora kinase isoforms, A and B (AURKA and AURKB), are expressed ubiquitously in mammals, whereas a third isoform, Aurora C (AURKC), is largely restricted to germ cells. Because AURKC is very similar to AURKB, based on sequence and functional analyses, why germ cells express AURKC is unclear. We report that Aurkc(-/-) females are subfertile, and that AURKB function declines as development progresses based on increasing severity of cytokinesis failure and arrested embryonic development. Furthermore, we find that neither Aurkb nor Aurkc is expressed after the one-cell stage, and that AURKC is more stable during maturation than AURKB using fluorescently tagged reporter proteins. In addition, Aurkc mRNA is recruited during maturation. Because maturation occurs in the absence of transcription, posttranscriptional regulation of Aurkc mRNA, coupled with the greater stability of AURKC protein, provides a means to ensure sufficient Aurora kinase activity, despite loss of AURKB, to support both meiotic and early embryonic cell divisions. These findings suggest a model for the presence of AURKC in oocytes: that AURKC compensates for loss of AURKB through differences in both message recruitment and protein stability. PMID- 22778419 TI - Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals. AB - During Mycobacterium tuberculosis infection, a population of bacteria likely becomes refractory to antibiotic killing in the absence of genotypic resistance, making treatment challenging. We describe an in vitro model capable of yielding a phenotypically antibiotic-tolerant subpopulation of cells, often called persisters, within populations of Mycobacterium smegmatis and M. tuberculosis. We find that persisters are distinct from the larger antibiotic-susceptible population, as a small drop in dissolved oxygen (DO) saturation (20%) allows for their survival in the face of bactericidal antibiotics. In contrast, if high levels of DO are maintained, all cells succumb, sterilizing the culture. With increasing evidence that bactericidal antibiotics induce cell death through the production of reactive oxygen species (ROS), we hypothesized that the drop in DO decreases the concentration of ROS, thereby facilitating persister survival, and maintenance of high DO yields sufficient ROS to kill persisters. Consistent with this hypothesis, the hydroxyl-radical scavenger thiourea, when added to M. smegmatis cultures maintained at high DO levels, rescues the persister population. Conversely, the antibiotic clofazimine, which increases ROS via an NADH-dependent redox cycling pathway, successfully eradicates the persister population. Recent work suggests that environmentally induced antibiotic tolerance of bulk populations may result from enhanced antioxidant capabilities. We now show that the small persister subpopulation within a larger antibiotic susceptible population also shows differential susceptibility to antibiotic induced hydroxyl radicals. Furthermore, we show that stimulating ROS production can eradicate persisters, thus providing a potential strategy to managing persistent infections. PMID- 22778420 TI - Enhancement of dendritic cell activation via CD40 ligand-expressing gammadelta T cells is responsible for protective immunity to Plasmodium parasites. AB - Previous reports have shown that gammadelta T cells are important for the elimination of malaria parasites in humans and mice. However, how gammadelta T cells are involved in protective immunity against blood-stage malaria remains unknown. We infected gammadelta T-cell-deficient (TCRdelta-KO) mice and control wild-type mice with Plasmodium berghei XAT, which is a nonlethal strain. Although infected red blood cells were eliminated within 30 d after infection, TCRdelta-KO mice could not clear the infected red blood cells, showed high parasitemia, and eventually died. Therefore, gammadelta T cells are essential for clearance of the parasites. Here, we found that gammadelta T cells play a key role in dendritic cell activation after Plasmodium infection. On day 5 postinfection, gammadelta T cells produced IFN-gamma and expressed CD40 ligand during dendritic cell activation. These results suggest that gammadelta T cells enhance dendritic cell activation via IFN-gamma and CD40 ligand-CD40 signaling. This hypothesis is supported strongly by the fact that in vivo induction of CD40 signaling prevented the death of TCRdelta-KO mice after infection with P. berghei XAT. This study improves our understanding of protective immunity against malaria and provides insights into gammadelta T-cell-mediated protective immunity against various infectious diseases. PMID- 22778421 TI - Cells gain traction in 3D. PMID- 22778422 TI - ATP-dependent conformational dynamics underlie the functional asymmetry of the replicative helicase from a minimalist eukaryote. AB - The heterohexameric minichromosome maintenance (MCM2-7) complex is an ATPase that serves as the central replicative helicase in eukaryotes. During initiation, the ring-shaped MCM2-7 particle is thought to open to facilitate loading onto DNA. The conformational state accessed during ring opening, the interplay between ATP binding and MCM2-7 architecture, and the use of these events in the regulation of DNA unwinding are poorly understood. To address these issues in isolation from the regulatory complexity of existing eukaryotic model systems, we investigated the structure/function relationships of a naturally minimized MCM2-7 complex from the microsporidian parasite Encephalitozoon cuniculi. Electron microscopy and small-angle X-ray scattering studies show that, in the absence of ATP, MCM2-7 spontaneously adopts a left-handed, open-ring structure. Nucleotide binding does not promote ring closure but does cause the particle to constrict in a two-step process that correlates with the filling of high- and low-affinity ATPase sites. Our findings support the idea that an open ring forms the default conformational state of the isolated MCM2-7 complex, and they provide a structural framework for understanding the multiphasic ATPase kinetics observed in different MCM2-7 systems. PMID- 22778423 TI - Population movement under extreme events. PMID- 22778424 TI - Regulatory switch enforced by basic helix-loop-helix and ACT-domain mediated dimerizations of the maize transcription factor R. AB - The maize R2R3-MYB regulator C1 cooperates with the basic helix-loop-helix (bHLH) factor R to activate the expression of anthocyanin biosynthetic genes coordinately. As is the case for other bHLH factors, R harbors several protein protein interaction domains. Here we show that not the classical but rather a briefly extended R bHLH region forms homodimers that bind canonical G-box DNA motifs. This bHLH DNA-binding activity is abolished if the C-terminal ACT (aspartokinase, chorismate, and TyrA) domain is licensed to homodimerize. Then the bHLH remains in the monomeric form, allowing it to interact with R interacting factor 1 (RIF1). In this configuration, the R-RIF1 complex is recruited to the promoters of a subset of anthocyanin biosynthetic genes, such as A1, through the interaction with its MYB partner C1. If, however, the ACT domain remains monomeric, the bHLH region dimerizes and binds to G-boxes present in several anthocyanin genes, such as Bz1. Our results provide a mechanism by which a dimerization domain in a bHLH factor behaves as a switch that permits distinct configurations of a regulatory complex to be tethered to different promoters. Such a combinatorial gene regulatory framework provides one mechanism by which genes lacking obviously conserved cis-regulatory elements are regulated coordinately. PMID- 22778425 TI - Redox alters yellow dragonflies into red. AB - Body color change associated with sexual maturation--so-called nuptial coloration -is commonly found in diverse vertebrates and invertebrates, and plays important roles for their reproductive success. In some dragonflies, whereas females and young males are yellowish in color, aged males turn vivid red upon sexual maturation. The male-specific coloration plays pivotal roles in, for example, mating and territoriality, but molecular basis of the sex-related transition in body coloration of the dragonflies has been poorly understood. Here we demonstrate that yellow/red color changes in the dragonflies are regulated by redox states of epidermal ommochrome pigments. Ratios of reduced-form pigments to oxidized-form pigments were significantly higher in red mature males than yellow females and immature males. The ommochrome pigments extracted from the dragonflies changed color according to redox conditions in vitro: from red to yellow in the presence of oxidant and from yellow to red in the presence of reductant. By injecting the reductant solution into live insects, the yellow-to red color change was experimentally reproduced in vivo in immature males and mature females. Discontinuous yellow/red mosaicism was observed in body coloration of gynandromorphic dragonflies, suggesting a cell-autonomous regulation over the redox states of the ommochrome pigments. Our finding extends the mechanical repertoire of pigment-based body color change in animals, and highlights an impressively simple molecular mechanism that regulates an ecologically important color trait. PMID- 22778426 TI - Compensatory mechanisms for ameliorating the fundamental trade-off between predator avoidance and foraging. AB - Most organisms face the problem of foraging and maintaining growth while avoiding predators. Typical animal responses to predator exposure include reduced feeding, elevated metabolism, and altered development rate, all of which can be beneficial in the presence of predators but detrimental in their absence. How then do animals balance growth and predator avoidance? In a series of field and greenhouse experiments, we document that the tobacco hornworm caterpillar, Manduca sexta, reduced feeding by 30-40% owing to the risk of predation by stink bugs, but developed more rapidly and gained the same mass as unthreatened caterpillars. Assimilation efficiency, extraction of nitrogen from food, and percent body lipid content all increased during the initial phase (1-3 d) of predation risk, indicating that enhanced nutritional physiology allows caterpillars to compensate when threatened. However, we report physiological costs of predation risk, including altered body composition (decreased glycogen) and reductions in assimilation efficiency later in development. Our findings indicate that hornworm caterpillars use temporally dynamic compensatory mechanisms that ameliorate the trade-off between predator avoidance and growth in the short term, deferring costs to a period when they are less vulnerable to predation. PMID- 22778428 TI - Recursive utility in a Markov environment with stochastic growth. AB - Recursive utility models that feature investor concerns about the intertemporal composition of risk are used extensively in applied research in macroeconomics and asset pricing. These models represent preferences as the solution to a nonlinear forward-looking difference equation with a terminal condition. In this paper we study infinite-horizon specifications of this difference equation in the context of a Markov environment. We establish a connection between the solution to this equation and to an arguably simpler Perron-Frobenius eigenvalue equation of the type that occurs in the study of large deviations for Markov processes. By exploiting this connection, we establish existence and uniqueness results. Moreover, we explore a substantive link between large deviation bounds for tail events for stochastic consumption growth and preferences induced by recursive utility. PMID- 22778427 TI - Remote control of renal physiology by the intestinal neuropeptide pigment dispersing factor in Drosophila. AB - The role of the central neuropeptide pigment-dispersing factor (PDF) in circadian timekeeping in Drosophila is remarkably similar to that of vasoactive intestinal peptide (VIP) in mammals. Like VIP, PDF is expressed outside the circadian network by neurons innervating the gut, but the function and mode of action of this PDF have not been characterized. Here we investigate the visceral roles of PDF by adapting cellular and physiological methods to the study of visceral responses to PDF signaling in wild-type and mutant genetic backgrounds. We find that intestinal PDF acts at a distance on the renal system, where it regulates ureter contractions. We show that PdfR, PDF's established receptor, is expressed by the muscles of the excretory system, and present evidence that PdfR-induced cAMP increases underlie the myotropic effects of PDF. These findings extend the similarities between PDF and VIP beyond their shared central role as circadian regulators, and uncover an unexpected endocrine mode of myotropic action for an intestinal neuropeptide on the renal system. PMID- 22778430 TI - Adaptive walks on the fitness landscape of music. PMID- 22778429 TI - Finding a druggable target for schizophrenia. PMID- 22778431 TI - Rise of interdisciplinary research on climate. AB - Until the middle of the 20th century, the discipline of climatology was a stagnant field preoccupied with regional statistics. It had little to do with meteorology, which itself was predominantly a craft that paid scant attention to physical theory. The Second World War and Cold War promoted a rapid growth of meteorology, which some practitioners increasingly combined with physical science in hopes of understanding global climate dynamics. However, the dozen or so scientific disciplines that had something to say about climate were largely isolated from one another. In the 1960s and 1970s, worries about climate change helped to push the diverse fields into contact. Scientists interested in climate change kept their identification with different disciplines but developed ways to communicate across the boundaries (for example, in large international projects). Around the turn of the 21st century, the Intergovernmental Panel on Climate Change institutionalized an unprecedented process of exchanges; its reports relied especially on computer modeling, which became a center of fully integrated interdisciplinary cooperation. PMID- 22778432 TI - Preparation of unnatural N-to-N and C-to-C protein fusions. AB - Standard genetic approaches allow the production of protein composites by fusion of polypeptides in head-to-tail fashion. Some applications would benefit from constructions that are genetically impossible, such as the site-specific linkage of proteins via their N or C termini, when a remaining free terminus is required for biological activity. We developed a method for the production of N-to-N and C to-C dimers, with full retention of the biological activity of both fusion partners and without inflicting chemical damage on the proteins to be joined. We use sortase A to install on the N or C terminus of proteins of interest the requisite modifications to execute a strain-promoted copper-free cycloaddition and show that the ensuing ligation proceeds efficiently. Applied here to protein protein fusions, the method reported can be extended to connecting proteins with any entity of interest. PMID- 22778433 TI - Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune responses. AB - A coordinated innate and adaptive immune response, orchestrated by antigen presenting cells (APCs), is required for effective clearance of influenza A virus (IAV). Although IAV primarily infects epithelial cells of the upper respiratory tract, APCs are also susceptible. To determine if virus transcription in these cells is required to generate protective innate and adaptive immune responses, we engineered IAV to be selectively attenuated in cells of hematopoietic origin. Incorporation of hematopoietic-specific miR-142 target sites into the nucleoprotein of IAV effectively silenced virus transcription in APCs, but had no significant impact in lung epithelial cells. Here we demonstrate that inhibiting IAV replication in APCs in vivo did not alter clearance, or the generation of IAV specific CD8 T cells, suggesting that cross-presentation is sufficient for cytotoxic T lymphocyte activation. In contrast, loss of in vivo virus infection, selectively in APCs, resulted in a significant reduction of retinoic acid inducible gene I-dependent type I IFN (IFN-I). These data implicate the formation of virus replication intermediates in APCs as the predominant trigger of IFN-I in vivo. Taking these data together, this research describes a unique platform to study the host response to IAV and provides insights into the mechanism of antigen presentation and the induction of IFN-I. PMID- 22778434 TI - A designed ankyrin repeat protein selected to bind to tubulin caps the microtubule plus end. AB - Microtubules are cytoskeleton filaments consisting of alphabeta-tubulin heterodimers. They switch between phases of growth and shrinkage. The underlying mechanism of this property, called dynamic instability, is not fully understood. Here, we identified a designed ankyrin repeat protein (DARPin) that interferes with microtubule assembly in a unique manner. The X-ray structure of its complex with GTP-tubulin shows that it binds to the beta-tubulin surface exposed at microtubule (+) ends. The details of the structure provide insight into the role of GTP in microtubule polymerization and the conformational state of tubulin at the very microtubule end. They show in particular that GTP facilitates the tubulin structural switch that accompanies microtubule assembly but does not trigger it in unpolymerized tubulin. Total internal reflection fluorescence microscopy revealed that the DARPin specifically blocks growth at the microtubule (+) end by a selective end-capping mechanism, ultimately favoring microtubule disassembly from that end. DARPins promise to become designable tools for the dissection of microtubule dynamic properties selective for either of their two different ends. PMID- 22778436 TI - Improving aerosol distributions below clouds by assimilating satellite-retrieved cloud droplet number. AB - Limitations in current capabilities to constrain aerosols adversely impact atmospheric simulations. Typically, aerosol burdens within models are constrained employing satellite aerosol optical properties, which are not available under cloudy conditions. Here we set the first steps to overcome the long-standing limitation that aerosols cannot be constrained using satellite remote sensing under cloudy conditions. We introduce a unique data assimilation method that uses cloud droplet number (N(d)) retrievals to improve predicted below-cloud aerosol mass and number concentrations. The assimilation, which uses an adjoint aerosol activation parameterization, improves agreement with independent N(d) observations and with in situ aerosol measurements below shallow cumulus clouds. The impacts of a single assimilation on aerosol and cloud forecasts extend beyond 24 h. Unlike previous methods, this technique can directly improve predictions of near-surface fine mode aerosols responsible for human health impacts and low cloud radiative forcing. Better constrained aerosol distributions will help improve health effects studies, atmospheric emissions estimates, and air-quality, weather, and climate predictions. PMID- 22778437 TI - Denaturant-dependent folding of GFP. AB - We use molecular simulations using a coarse-grained model to map the folding landscape of Green Fluorescent Protein (GFP), which is extensively used as a marker in cell biology and biotechnology. Thermal and Guanidinium chloride (GdmCl) induced unfolding of a variant of GFP, without the chromophore, occurs in an apparent two-state manner. The calculated midpoint of the equilibrium folding in GdmCl, taken into account using the Molecular Transfer Model (MTM), is in excellent agreement with the experiments. The melting temperatures decrease linearly as the concentrations of GdmCl and urea are increased. The structural features of rarely populated equilibrium intermediates, visible only in free energy profiles projected along a few order parameters, are remarkably similar to those identified in a number of ensemble experiments in GFP with the chromophore. The excellent agreement between simulations and experiments show that the equilibrium intermediates are stabilized by the chromophore. Folding kinetics, upon temperature quench, show that GFP first collapses and populates an ensemble of compact structures. Despite the seeming simplicity of the equilibrium folding, flux to the native state flows through multiple channels and can be described by the kinetic partitioning mechanism. Detailed analysis of the folding trajectories show that both equilibrium and several kinetic intermediates, including misfolded structures, are sampled during folding. Interestingly, the intermediates characterized in the simulations coincide with those identified in single molecule pulling experiments. Our predictions, amenable to experimental tests, show that MTM is a practical way to simulate the effect of denaturants on the folding of large proteins. PMID- 22778438 TI - Redox systematics of a magma ocean with variable pressure-temperature gradients and composition. AB - Oxygen fugacity in metal-bearing systems controls some fundamental aspects of the geochemistry of the early Earth, such as the FeO and siderophile trace element content of the mantle, volatile species that influence atmospheric composition, and conditions for organic compounds synthesis. Redox and metal-silicate equilibria in the early Earth are sensitive to oxygen fugacity (fO(2)), yet are poorly constrained in modeling and experimentation. High pressure and temperature experimentation and modeling in metal-silicate systems usually employs an approximation approach for estimating fO(2) that is based on the ratio of Fe and FeO [called "DeltaIW (ratio)" hereafter]. We present a new approach that utilizes free energy and activity modeling of the equilibrium: Fe + SiO(2) + O(2) = Fe(2)SiO(4) to calculate absolute fO(2) and relative to the iron-wustite (IW) buffer at pressure and temperature [DeltaIW (P,T)]. This equilibrium is considered across a wide range of pressures and temperatures, including up to the liquidus temperature of peridotite (4,000 K at 50 GPa). Application of DeltaIW (ratio) to metal-silicate experiments can be three or four orders of magnitude different from DeltaIW (P,T) values calculated using free energy and activity modeling. We will also use this approach to consider the variation in oxygen fugacity in a magma ocean scenario for various thermal structures for the early Earth: hot liquidus gradient, 100 degrees C below the liquidus, hot and cool adiabatic gradients, and a cool subsolidus adiabat. The results are used to assess the effect of increasing P and T, changing silicate composition during accretion, and related to current models for accretion and core formation in the Earth. The fO(2) in a deep magma ocean scenario may become lower relative to the IW buffer at hotter and deeper conditions, which could include metal entrainment scenarios. Therefore, fO(2) may evolve from high to low fO(2) during Earth (and other differentiated bodies) accretion. Any modeling of core formation and metal silicate equilibrium should take these effects into account. PMID- 22778439 TI - Large enantiomeric excesses in primitive meteorites and the diverse effects of water in cosmochemical evolution. AB - Carbonaceous chondrites are meteoritic fragments of asteroids that avoided the geological reprocessing of larger planets and allow laboratory probing of early solar-nebula materials. Among these, Renazzo-type (CR) chondrites found in Antarctica appear remarkably pristine and are distinguished by abundant organic materials and water-soluble molecules such as amino acids and ammonia. We present a comprehensive analysis of the organic composition of selected CR meteorites of different petrographic classification and compare compounds' abundance and distribution as they may relate to asteroidal aqueous processing and concomitant evolution of the mineral phases. We found that several CR compounds such as amino acids and sugar alcohols are fully represented in stones with no or minimal water exposure indicating a formation that, if solar, preceded parent body processes. The most pristine CRs also revealed natal enantiomeric excesses (ee) of up to 60%, much larger than ever recorded. However, aqueous alteration appears to affect CR soluble organic composition and abundances, in particular some diastereomeric amino acids may gauge its extent by the consequent racemization of their ee. PMID- 22778440 TI - Magnetic characterization of isolated candidate vertebrate magnetoreceptor cells. AB - Over the past 50 y, behavioral experiments have produced a large body of evidence for the existence of a magnetic sense in a wide range of animals. However, the underlying sensory physiology remains poorly understood due to the elusiveness of the magnetosensory structures. Here we present an effective method for isolating and characterizing potential magnetite-based magnetoreceptor cells. In essence, a rotating magnetic field is employed to visually identify, within a dissociated tissue preparation, cells that contain magnetic material by their rotational behavior. As a tissue of choice, we selected trout olfactory epithelium that has been previously suggested to host candidate magnetoreceptor cells. We were able to reproducibly detect magnetic cells and to determine their magnetic dipole moment. The obtained values (4 to 100 fAm(2)) greatly exceed previous estimates (0.5 fAm(2)). The magnetism of the cells is due to a MUm-sized intracellular structure of iron-rich crystals, most likely single-domain magnetite. In confocal reflectance imaging, these produce bright reflective spots close to the cell membrane. The magnetic inclusions are found to be firmly coupled to the cell membrane, enabling a direct transduction of mechanical stress produced by magnetic torque acting on the cellular dipole in situ. Our results show that the magnetically identified cells clearly meet the physical requirements for a magnetoreceptor capable of rapidly detecting small changes in the external magnetic field. This would also explain interference of ac powerline magnetic fields with magnetoreception, as reported in cattle. PMID- 22778441 TI - Tumor radiation response enhancement by acoustical stimulation of the vasculature. AB - We have discovered that ultrasound-mediated microbubble vascular disruption can enhance tumor responses to radiation in vivo. We demonstrate this effect using a human PC3 prostate cancer xenograft model. Results indicate a synergistic effect in vivo with combined single treatments of ultrasound-stimulated microbubble vascular perturbation and radiation inducing an over 10-fold greater cell kill with combined treatments. We further demonstrate with experiments in vivo that induction of ceramide-related endothelial cell apoptosis, leading to vascular disruption, is a causative mechanism. In vivo experiments with ultrasound and bubbles permit radiation doses to be decreased significantly for comparable effect. We envisage this unique combined ultrasound-based vascular perturbation and radiation treatment method being used to enhance the effects of radiation in a tumor, leading to greater tumor eradication. PMID- 22778442 TI - Simple few-state models reveal hidden complexity in protein folding. AB - Markov state models constructed from molecular dynamics simulations have recently shown success at modeling protein folding kinetics. Here we introduce two methods, flux PCCA+ (FPCCA+) and sliding constraint rate estimation (SCRE), that allow accurate rate models from protein folding simulations. We apply these techniques to fourteen massive simulation datasets generated by Anton and Folding@home. Our protocol quantitatively identifies the suitability of describing each system using two-state kinetics and predicts experimentally detectable deviations from two-state behavior. An analysis of the villin headpiece and FiP35 WW domain detects multiple native substates that are consistent with experimental data. Applying the same protocol to GTT, NTL9, and protein G suggests that some beta containing proteins can form long-lived native like states with small register shifts. Even the simplest protein systems show folding and functional dynamics involving three or more states. PMID- 22778443 TI - Stabilization of vaccines and antibiotics in silk and eliminating the cold chain. AB - Sensitive biological compounds, such as vaccines and antibiotics, traditionally require a time-dependent "cold chain" to maximize therapeutic activity. This flawed process results in billions of dollars worth of viable drug loss during shipping and storage, and severely limits distribution to developing nations with limited infrastructure. To address these major limitations, we demonstrate self standing silk protein biomaterial matrices capable of stabilizing labile vaccines and antibiotics, even at temperatures up to 60 degrees C over more than 6 months. Initial insight into the mechanistic basis for these findings is provided. Importantly, these findings suggest a transformative approach to the cold chain to revolutionize the way many labile therapeutic drugs are stored and utilized throughout the world. PMID- 22778444 TI - Transcriptome and methylome interactions in rice hybrids. AB - DNA methylation is a heritable epigenetic mark that controls gene expression, is responsive to environmental stresses, and, in plants, may also play a role in heterosis. To determine the degree to which DNA methylation is inherited in rice, and how it both influences and is affected by transcription, we performed genome wide measurements of these patterns through an integrative analysis of bisulfite sequencing, RNA-sequencing, and siRNA-sequencing data in two inbred parents of the Nipponbare (NPB) and indica (93-11) varieties of rice and their hybrid offspring. We show that SNPs occur at a rate of about 1/253 bp between the two parents and that these are faithfully transmitted into the hybrids. We use the presence of these SNPs to reconstruct the two chromosomes in the hybrids according to their parental origin. We found that, unlike genetic inheritance, epigenetic heritability is quite variable. Cytosines were found to be differentially methylated (epimutated) at a rate of 7.48% (1/15 cytosines) between the NPB and 93-11 parental strains. We also observed that 0.79% of cytosines were epimutated between the parent and corresponding hybrid chromosome. We found that these epimutations are often clustered on the chromosomes, with clusters representing 20% of all epimutations between parental ecotypes, and 2-5% in F1 plants. Epimutation clusters are also strongly associated with regions where the production of siRNA differs between parents. Finally, we identified genes with both allele-specific expression patterns that were strongly inherited as well as those differentially expressed between hybrids and the corresponding parental chromosome. We conclude that much of the misinheritance of expression levels is likely caused by epimutations and trans effects. PMID- 22778445 TI - Geochemical evidence for possible natural migration of Marcellus Formation brine to shallow aquifers in Pennsylvania. AB - The debate surrounding the safety of shale gas development in the Appalachian Basin has generated increased awareness of drinking water quality in rural communities. Concerns include the potential for migration of stray gas, metal rich formation brines, and hydraulic fracturing and/or flowback fluids to drinking water aquifers. A critical question common to these environmental risks is the hydraulic connectivity between the shale gas formations and the overlying shallow drinking water aquifers. We present geochemical evidence from northeastern Pennsylvania showing that pathways, unrelated to recent drilling activities, exist in some locations between deep underlying formations and shallow drinking water aquifers. Integration of chemical data (Br, Cl, Na, Ba, Sr, and Li) and isotopic ratios ((87)Sr/(86)Sr, (2)H/H, (18)O/(16)O, and (228)Ra/(226)Ra) from this and previous studies in 426 shallow groundwater samples and 83 northern Appalachian brine samples suggest that mixing relationships between shallow ground water and a deep formation brine causes groundwater salinization in some locations. The strong geochemical fingerprint in the salinized (Cl > 20 mg/L) groundwater sampled from the Alluvium, Catskill, and Lock Haven aquifers suggests possible migration of Marcellus brine through naturally occurring pathways. The occurrences of saline water do not correlate with the location of shale-gas wells and are consistent with reported data before rapid shale-gas development in the region; however, the presence of these fluids suggests conductive pathways and specific geostructural and/or hydrodynamic regimes in northeastern Pennsylvania that are at increased risk for contamination of shallow drinking water resources, particularly by fugitive gases, because of natural hydraulic connections to deeper formations. PMID- 22778446 TI - Sensing and decision-making in random search. AB - Many organisms locate resources in environments in which sensory signals are rare, noisy, and lack directional information. Recent studies of search in such environments model search behavior using random walks (e.g., Levy walks) that match empirical movement distributions. We extend this modeling approach to include searcher responses to noisy sensory data. We explore the consequences of incorporating such sensory measurements into search behavior using simulations of a visual-olfactory predator in search of prey. Our results show that including even a simple response to noisy sensory data can dominate other features of random search, resulting in lower mean search times and decreased risk of long intervals between target encounters. In particular, we show that a lack of signal is not a lack of information. Searchers that receive no signal can quickly abandon target-poor regions. On the other hand, receiving a strong signal leads a searcher to concentrate search effort near targets. These responses cause simulated searchers to exhibit an emergent area-restricted search behavior similar to that observed of many organisms in nature. PMID- 22778447 TI - In vivo differentiation of complementary contrast media at dual-energy CT. AB - PURPOSE: To evaluate the feasibility of using a commercially available clinical dual-energy computed tomographic (CT) scanner to differentiate the in vivo enhancement due to two simultaneously administered contrast media with complementary x-ray attenuation ratios. MATERIALS AND METHODS: Approval from the institutional animal care and use committee was obtained, and National Institutes of Health guidelines for the care and use of laboratory animals were observed. Dual-energy CT was performed in a set of iodine and tungsten solution phantoms and in a rabbit in which iodinated intravenous and bismuth subsalicylate oral contrast media were administered. In addition, a second rabbit was studied after intravenous administration of iodinated and tungsten cluster contrast media. Images were processed to produce virtual monochromatic images that simulated the appearance of conventional single-energy scans, as well as material decomposition images that separate the attenuation due to each contrast medium. RESULTS: Clear separation of each of the contrast media pairs was seen in the phantom and in both in vivo animal models. Separation of bowel lumen from vascular contrast medium allowed visualization of bowel wall enhancement that was obscured by intraluminal bowel contrast medium on conventional CT scans. Separation of two vascular contrast media in different vascular phases enabled acquisition of a perfectly coregistered CT angiogram and venous phase-enhanced CT scan simultaneously in a single examination. CONCLUSION: Commercially available clinical dual-energy CT scanners can help differentiate the enhancement of selected pairs of complementary contrast media in vivo. PMID- 22778448 TI - Congenital epulis. AB - Congenital epulis is a rare, soft-tissue benign condition that presents at birth. It arises from the alveolar mucosa and occurs more frequently in the maxilla, mainly in the frontal region. This condition may interfere with respiration, feeding or lip closure. Surgical excision is the only possible treatment, although spontaneous regression has been reported. This article presents the case of a female infant with a solid ovoid mass protruding from the oral cavity. Treatment of this lesion was surgical, and histopathological examination confirmed the clinical diagnosis of congenital epulis. Postsurgical follow-up was without complications; examination of the infant 5 months later has revealed only mild left frontal alveolar ridge hypoplasia without any sign of recurrence. PMID- 22778449 TI - Where is reactivation after a long latency? AB - The authors present a 90-year-old woman with unilateral glossopharyngeal, vagal and spinal accessory cranial nerve palsy along with pharyngeal and laryngeal vesicular eruptions. She was diagnosed with herpes zoster based on PCR testing on vesicular fluid for varicella-zoster virus (VZV). Reactivation of VZV in the head and neck region can cause life-threatening neurologic sequelae. Clinicians should be alert to the possibility of herpes zoster in a case of unilateral multiple cranial neuropathies and rapid combination therapy with acyclovir and corticosteroid should be initiated. PMID- 22778450 TI - Intestinal efflorescences in disseminated varicella zoster infection. PMID- 22778451 TI - An atypical case of purple glove syndrome: an avoidable adverse event. AB - A 73-year-old man presented in status epilepticus. He had a long history of epilepsy for which he was treated with regular phenytoin and phenobarbitone. On admission, his phenytoin level was found to be subtherapeutic and was treated with rectal diazepam and intravenous lorazepam. He was later started on an infusion of phenytoin in preparation to restart his oral medication. The medication was delivered via a peripheral cannula in his forearm. Five days later, he developed redness and swelling of this arm followed by the appearance of a large ulcer. After ruling out infective causes and a compartment syndrome it was felt that the patient had developed a delayed purple glove syndrome secondary to intravenous phenytoin. Following 7 days of regular saline irrigation and dressing changes, the erythema improved and the ulcer showed signs of healing, and eventually resolved. PMID- 22778452 TI - Parallel haemodialysis and surgery saves a life after massive overdose of potassium pills. AB - Severe poisoning with potassium pills is rare but patients may present with serious cardiovascular symptoms requiring immediate and effective treatment. A 30 year-old healthy woman presented to the emergency department after ingestion of 300 slow-release pills of potassium-chloride with serum potassium of 9.5 mmol/l, and poor cardiovascular function. Gastric lavage was performed with poor outcome. Despite intensive medical treatment serum potassium remained very high around 9 mmol/l. Haemodialysis was initiated but despite ongoing dialysis, potassium increased to 10.3 mmol/l. Hence, a parallel dialysis was started and after 4 h of parallel dialysis, serum potassium decreased to 6.4 mmol/l. An x-ray revealed large amounts of pills remaining in the stomach and the surgeon was able to remove about 200 pills through an acute laparotomy. The patient recovered slowly thereafter, but later developed a gastric stricture and pulmonary embolism. PMID- 22778453 TI - Papillary carcinoma of thyroid arising from ectopic thyroid tissue inside branchial cleft cyst: a rare case. AB - Ectopic thyroid glands generally occur in the midline as a result of abnormal median migration. The presence of these ectopic glands, lateral to the midline is rare. Here, the authors present one case of papillary carcinoma of thyroid arising from an ectopic thyroid tissue in branchial cleft cyst presented as a swelling in lateral neck diagnosed after cystectomy. Total thyroidectomy and neck dissection were done to rule out occult primary carcinoma of thyroid. Histopathology report showed thyroid and lymph nodes were normal. PMID- 22778454 TI - Aesthetic management of gingival recession by root biomodification with carbon dioxide laser and subepithelial connective tissue graft with lateral repositioned flap technique. AB - Localised gingival recessions continue to represent an important aesthetic condition requiring treatment in periodontics. Various techniques have been tried to treat exposed root surfaces to improve aesthetics with high percentage of success and minimal discomfort. Root biomodification is done to improve the predictability of these procedures. This clinical report describes periodontal plastic procedure involving subepithelial connective tissue graft with lateral repositioned flap technique and root biomodification with CO(2) laser for the management of gingival recession. PMID- 22778455 TI - Bradycardia following retinoic acid differentiation syndrome in a patient with acute promyelocytic leukaemia. AB - The authors describe a 28-year-old woman with newly diagnosed acute promyelocytic leukaemia (APL), who developed junctional bradycardia after receiving the molecular-targeted therapy all-trans retinoic acid (ATRA) and the anthracycline based chemotherapeutic agent idarubicin following sepsis and the APL differentiation syndrome. The patient was asymptomatic of the bradycardia. Electrolytes and cardiac imaging were unremarkable. No other cases have been reported in this context and the mechanisms of the sinus node dysfunction are unclear. The patient achieved normal sinus rhythm after ATRA was withheld. The patient recovered and went on to achieve complete remission after re-starting ATRA and idarubicin. PMID- 22778456 TI - Fentanyl-clarithromycin interaction. AB - This case describes an incident where a patient with breast cancer and bone metastases, who was using a fentanyl patch, was started on a course of clarithromycin and experienced a respiratory arrest 2 days later. She was a hospital inpatient at the time and was treated with naloxone and the fentanyl patch was stopped at the time of the reaction. She recovered but was left without pain relief until seen in clinic by the palliative care consultant who restarted the fentanyl patch without further problems. PMID- 22778457 TI - Piperacillin/tazobactam induced thrombocytopaenia--a delayed response. AB - A 48-year-old lady who presented with sepsis secondary to a pelvi-ureteric junction obstruction was treated with an extended course of piperacillin/tazobactam. Four days after completing the course she developed thrombocytopaenia. Intravenous immunoglobulin was required to bring her platelet count back to normal. In the absence of other causes the authors believe that a delayed reaction to piperacillin/tazobactam was the cause of her thrombocytopaenia. PMID- 22778458 TI - Primary mesenteric hydatid cyst. AB - Hydatid disease mostly caused by Echinococcus granulosus is a common parasitic infestation of the liver. Most common sites are liver (70%) and lungs (25%). Intraperitoneal hydatid cyst is found in 13% and it is usually secondary to rupture of primary hepatic cyst. Primary intraperitoeal hydatid cyst is rare (2%). Primary hydatid cyst in mesentery is very rare. In this article, the author presents a case of primary mesenteric hydatid cyst with chronic pain in lower abdomen. PMID- 22778459 TI - Nasopharynx carcinoma: a rare primary for bilateral breast metastasis. AB - To conclude, bilateral breast metastases from the undifferentiated carcinoma of nasopharynx are rare. Breast metastases are commonly confused with the more common primary carcinoma of breast. Diagnosis is based on the core needle biopsy of the lesion which is helpful in the appropriate treatment planning of the patient. PMID- 22778460 TI - Successful treatment of two refractory venous stasis ulcers treated with a novel poly-N-acetyl glucosamine-derived membrane. AB - Standard of care for venous leg ulcers (VLUs) consists of the application of compression bandages or stockings and of local moist wound care. While the majority of patients heal with the above mentioned treatments some ulcers become refractory to treatment causing significant disability and costs. The authors present the observation made on two patients with VLUs who had failed to respond to a comprehensive state of the art wound care approach for 11 and 3 years respectively. Both patients were treated with a poly-N-acetyl glucosamine-derived membrane (pGlcNAc) (Talymed, Marine Polymer Technologies, Danvers, Massachusetts, USA) in addition to compression bandaging. Both patients healed within 6 weeks of the first application of pG1cNAc. The authors present two cases of VLUs that had been considered non-healable that were successfully treated in a very short period of time with the application of a novel technology. PMID- 22778461 TI - Unusual association of Arnold-Chiari malformation and vitamin B12 deficiency. AB - Arnold-Chiari malformations are a group of congenital or acquired defects associated with the displacement of cerebellar tonsils into the spinal canal. First described by Chiari (1891), this has various grades of severity and involves various parts of neuraxis, for example, cerebellum and its outputs, neuro-otological system, lower cranial nerves, spinal sensory and motor pathways. The symptomatology of Arnold-Chiari malformations may mimic multiple sclerosis, primary headache syndromes, spinal tumours and benign intracranial hypertension. We highlighted a case of Chiari type I malformation, who presented with posterolateral ataxia associated with significant vitamin B(12) deficiency. The patient was supplemented with vitamin B(12) injections and showed remarkable improvement at follow-up after 3 months. PMID- 22778462 TI - Caesarean scar pregnancy. AB - Faced with difficulty discriminating between placenta and myometrium in a patient with three previous caesarean sections, MRI provided definitive diagnosis of caesarean scar pregnancy, allowing for a save and uneventful planned surgical procedure. PMID- 22778463 TI - A difficult case of fever of unknown origin. AB - A 57-year-old holidaymaker in Madeira was airlifted to England with a 4-week history of fever, limb weakness and hypophonia. Having undergone a range of investigations during his hospital admission abroad - including ultrasound, CT, echocardiogram and lumbar puncture - the patient arrived without any explanatory diagnosis. At presentation, the only investigatory positives were raised blood inflammatory markers and a, previously unidentified, 'old left frontal infarct' found on head CT. A broad infective and immunological screen proved negative, raising the possibility of vasculitis. Finally, the presence of subacute cerebral and renal infarcts identified on MRI and CT in combination with a negative antineutrophil cytoplasmic antibodies (ANCA) test and distinctive muscle biopsy features confirmed the clinical suspicion of polyarteritis nodosa. An immunosuppressive regime of glucocorticoid therapy and cyclophosphamide were initiated with immediate significant clinical improvement. PMID- 22778464 TI - Middle cranial fossa cystic schwannoma. AB - The authors present the unusual case of a 37-year-old man, with a history of hepatitis C, presenting with a 3 year history of progressive trigeminal, facial and vestibular nerve defects. Intracranial imaging demonstrated a cystic middle and posterior fossa lesion, that was ultimately diagnosed as a cystic trigeminal schwannoma. Due to the uncertainties of diagnosis he was managed in two stages with an open biopsy and then a subsequent partial resection. Surveillance of the tumour remnant is planned. The rare nature of this diagnosis is discussed, along with the more common findings in intracranial schwannoma, and the wide differential to be considered. Briefly, the authors describe the surgical option for a complex multi-fossa schwannoma and the importance of the multi-disciplinary team in the diagnosis and management of such patients. PMID- 22778465 TI - Tuberculous meningitis, an unusual presentation in a young lady. AB - A 37-year-old Persian-speaking woman presented with epigastric pain, vomiting and non-specific frontal headache. Examination was unremarkable except for an isolated sixth nerve palsy found a few days after admission. Blood results were normal, as was the chest radiograph and the CT scan of the head. Initial cerebrospinal fluid (CSF) analysis revealed a significantly elevated protein level with reduced glucose, as well as CSF lymphocytosis. Tuberculosis (TB) meningitis was considered and she was commenced on anti-TB treatment before confirmation of the diagnosis. A full contact tracing was performed with regular follow-up with TB nurses. When she was seen in the clinic a month later, her symptoms had subsided completely. PMID- 22778466 TI - Intraoral schwannoma--a report of two cases. AB - Schwannomas, also known as neurilemmomas, are uncommon neoplasms, derived from schwann cells. These neoplasms, although rare, should be considered in the differential diagnosis of slow growing tumour masses of the oral cavity. The growth of these tumours sometimes causes displacement and compression of the nerve of origin, giving rise to clinical signs and symptoms. It can develop at any age and there is no sex predilection. Intraorally, the tongue is the most common site followed by the palate, floor of the mouth, buccal mucosa, lips and jaws. Surgical excision is the treatment of choice for schwannomas, with few reports of recurrence or malignant transformation. In this paper, the authors report two cases of patients with intraoral schwannoma, where the preoperative clinical diagnosis was inconclusive and final diagnosis was established based on radiographic and histopathological examination. PMID- 22778467 TI - Spontaneous haemorrhagic perforation of gallbladder in acute cholecystitis as a complication of antiplatelet, immunosuppressant and corticosteroid therapy. AB - An older lady presented 1 week after being discharged from hospital with acute cholecystitis. She suffered a sudden onset lower abdominal pain and was in hypovolaemic shock upon arrival. It was noted that she had been on antiplatelet therapy after suffering a recent myocardial infarction, an immunosuppressor and steroids for rheumatoid arthritis. Her admission bloods revealed a platelet count of 83 with normal clotting factors. After resuscitation, a CT scan confirmed fluid in the abdomen possibly arising from the right subhepatic space. During laparotomy, bleeding was noted from a perforated and ischaemic-looking gallbladder, with an intact cystic artery and duct and no biliary calculi evident. The gallbladder was removed and the patient was transferred to intensive therapy unit. She recovered well within the subsequent 8 days and was discharged. Her histology described 'haemorrhage within the gallbladder wall along with oedema, fibrosis and patchy inflammation and no signs of malignancy or gangrene'. PMID- 22778468 TI - If at first you do not succeed, think again! AB - The authors describe a case of platypnoea orthodeoxia syndrome in an 83-year-old man with a fenestrated atrial septal defect and severe coronary artery disease. The patient had been admitted to hospital six times in the previous year with acute breathlessness, attributed to paroxysmal atrial fibrillation. The patient's symptoms resolved completely following surgical repair of the defect and coronary artery bypass grafting. PMID- 22778469 TI - Isolated trochlear nerve palsy with perimesencephalic subarachnoid haemorrhage. AB - Perimesencephalic subarachnoid haemorrhage is usually asymptomatic other than meningeal irritation sign. The authors report a case of subarachnoid haemorrhage at the quadrigeminal cistern showing ipsilateral trochlear nerve palsy and discuss the pathogenesis. A 71-year-old man with a history of diabetes mellitus and acute myocardial infarction presented with diplopia. He underwent CT, which revealed subarachnoid haemorrhage at the left quadrigeminal cistern. Neurological examination revealed left isolated trochlear nerve palsy, with results otherwise normal. The diagnosis of perimesencephalic subarachnoid haemorrhage was established on neuroimaging. The amount of haemorrhage is related to symptoms. A dense clot in the quadrigeminal cistern might have been the cause of trochlear nerve palsy. PMID- 22778470 TI - Pelvi-ureteric junction obstruction in autosomal-dominant polycystic kidney disease: an association yet to be reported. AB - Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited renal cystic disease. It is characterised by the development of renal parenchymal cysts and a variety of other extrarenal manifestations. Pelvi-ureteric junction (PUJ) obstruction has not been described in association with ADPKD in the literature. We present a case of a 23-year-old man presenting with bilateral flank pain. On evaluation he was diagnosed to have ADPKD with bilateral renal calculi and left-sided PUJ obstruction. He underwent successful right percutaneous nephrolithotomy and left laparoscopic dismembered pyeloplasty with simultaneous stone removal. PMID- 22778471 TI - Paradoxical extensive thoracolumbosacral arachnoiditis in a treated patient of tuberculous meningitis. PMID- 22778472 TI - MRI for the detection of prostate cancer origin vertebral metastases in the preosteoblastic phase. AB - This report describes the case of a gentleman aged 59 years presenting with low back pain, who had underwent radical prostatectomy for prostate cancer 8 years ago. On evaluation, a slightly elevated serum alkaline-phosphatase level prompted a search for bone metastases. Although x-ray radiography and a bone scan were apparently normal, an MRI scan revealed the presence of metastatic marrow infiltration in the lumbar vertebrae. The patient subsequently was initiated on therapy with androgen-deprivation therapy and bisphosphonates, and currently enjoys symptom-free and progression-free survival. The images in this paper intend to impress upon the limitations of bone scan and x-ray radiography with regard to the detection of vertebral marrow infiltration in the absence of cortical bone invasion. In addition, a brief review of the pathophysiology of vertebral metastases arising from prostate cancer is included. PMID- 22778473 TI - A rare cause of upper airway obstruction in neonates. PMID- 22778474 TI - Giant verrucous carcinoma of the lower extremity in women with dementia. AB - We present the case of an 81-year-old woman with dementia and a giant exophytic ulcerated tumour, which covered most of the lower leg and the dorsum of the foot and emitted a foul smell. The patient had chronic venous insufficiency for 30 years, and previously (appr. 20 years ago) had a squamous cell carcinoma in the same location (right lower leg) that could be treated surgically. The dermatopathological examination of a large excisional biopsy revealed a highly differentiated verrucous carcinoma (formerly referred to as papillomatosis cutis carcinoides). Pathologically modified lymph nodes (suspicious of lymphatic metastases) were observed. Possible treatment options (surgery, intralesional and systemic treatment) were discussed. Finally, due to extension, location of the tumour and the age and co-morbidities of the patient, a decision was made to perform radiation therapy. PMID- 22778475 TI - Chronic cystoid macular oedema treated with intravitreal dobesilate. AB - Dobesilate is an anti-inflammatory and antipermeability agent. Intravitreal administration of this compound is a therapeutically beneficial agent in the treatment of chronic cystoid macular oedema. PMID- 22778476 TI - Pyopneumopericardium. PMID- 22778477 TI - A solid organising cryptogenic liver abscess and its association with a colonic tubullovillous adenoma. AB - Cryptogenic liver abscess (CLA) is a well-known disease entity that has puzzled clinicians for centuries. With the advancement of diagnostic modalities, comes the decreasing incidence of liver abscess labelled as 'cryptogenic' in nature. Colonic diseases have been identified as a possible underlying condition found in patients with liver abscesses. Although rare, tubullovillous adenomas have been implicated as one of the colonic causes of a CLA. We present a case of a CLA in a 53-year-old man with a potentially associated tubullovillous adenoma found via colonoscopy. PMID- 22778478 TI - Ectatic left circumflex artery with fistula to coronary sinus presenting with inferior wall myocardial infarction. AB - Coronary arteriovenous fistulae are a rare but potentially curable cause of ischaemic heart disease and should be considered as a differential diagnosis especially in patients lacking classical risk factors for coronary artery disease. We discuss one such case of cardiac ischaemia resulting from a coronary arteriovenous fistula. While there are sporadic case reports of similar patients in medical literature, our patient is the first reported case of ST-elevation myocardial infarction secondary to the fistulous connection. PMID- 22778479 TI - Recurrent vitreous haemorrhage and epidural haematoma in a child with hypofibrinogenaemia. AB - A 14-month-old male infant was brought by parents for redness of the right eye of 18 days duration. Exam and B-scan ultrasonography revealed total hyphema, dense vitreous haemorrhage and lens subluxation in the right eye while CT disclosed right small epidural haematoma. The left eye had neither retinal haemorrhage nor disc oedema. There was no sign of shaken baby syndrome. Fibrinogen level in the blood was very low. The parents are first-degree cousins with two family members having hypofibrinogenaemia. Vitreous haemorrhage recurred after surgical intervention resulting in phthisis and loss of vision. Hypofibrinogenaemia needs to be included in the differential diagnosis of ocular haemorrhage and vision loss. PMID- 22778480 TI - Don't forget 'simple' causes of abdominal pain. PMID- 22778481 TI - S1Q3T3 pattern leading to early diagnosis of pulmonary embolism. PMID- 22778488 TI - Synthesis and Preliminary Biological Study of Bisindolylmethanes Accessed by an Acid-Catalyzed Hydroarylation of Vinylindoles. AB - An acid-catalyzed hydroarylation reaction of vinyl indoles is reported, which tolerates a wide range of heterocycles as the exogenous nucleophile such as indoles, pyrroles, and indolizines. The method rapidly accesses the biologically relevant bisindolylmethane scaffold in good to excellent yields. Evaluation of the biological activity of several synthesized analogues reveals cytotoxic activity against and selectivity for the MCF-7 breast cancer cell line. PMID- 22778489 TI - Growth and remodeling of the left ventricle: A case study of myocardial infarction and surgical ventricular restoration. AB - Cardiac growth and remodeling in the form of chamber dilation and wall thinning are typical hallmarks of infarct-induced heart failure. Over time, the infarct region stiffens, the remaining muscle takes over function, and the chamber weakens and dilates. Current therapies seek to attenuate these effects by removing the infarct region or by providing structural support to the ventricular wall. However, the underlying mechanisms of these therapies are unclear, and the results remain suboptimal. Here we show that myocardial infarction induces pronounced regional and transmural variations in cardiac form. We introduce a mechanistic growth model capable of predicting structural alterations in response to mechanical overload. Under a uniform loading, this model predicts non-uniform growth. Using this model, we simulate growth in a patient-specific left ventricle. We compare two cases, growth in an infarcted heart, pre-operative, and growth in the same heart, after the infarct was surgically excluded, post operative. Our results suggest that removing the infarct and creating a left ventricle with homogeneous mechanical properties does not necessarily reduce the driving forces for growth and remodeling. These preliminary findings agree conceptually with clinical observations. PMID- 22778490 TI - Cationic liposome-nucleic acid complexes: liquid crystal phases with applications in gene therapy. AB - Cationic liposome (CL) carriers of nucleic acids are primarily studied because of their applications in gene delivery and gene silencing with CL-DNA and CL-siRNA (short-interfering RNA) complexes, respectively, and their implications to ongoing clinical gene therapy trials worldwide. A series of synchrotron-based small-angle-x-ray scattering studies, dating back to 1997, has revealed that CL nucleic acid complexes spontaneously assemble into distinct novel liquid crystalline phases of matter. Significantly, transfection efficiency (TE; a measure of expression of an exogenous gene that is transferred into the cell by the lipid carrier) has been found to be dependent on the liquid crystalline structure of complexes, with lamellar complexes showing strong dependence on membrane charge density (sigma(M)) and non-lamellar complexes exhibiting TE behavior independent ofsigma(M). The review describes our current understanding of the structures of different liquid crystalline CL-nucleic acid complexes including the recently described gyroid cubic phase of CL-siRNA complexes used in gene silencing. It further makes apparent that the long-term goal of developing optimized liquid crystalline CL-nucleic acid complexes for successful medical applications requires a comprehensive understanding of the nature of the interactions of distinctly structured complexes with cell membranes and events leading to release of active nucleic acids within the cell cytoplasm. PMID- 22778491 TI - Development of Dual-Retrieval Processes in Recall: Learning, Forgetting, and Reminiscence. AB - We investigated the development of dual-retrieval processes with a low-burden paradigm that is suitable for research with children and neurocognitively impaired populations (e.g., older adults with mild cognitive impairment or dementia). Rich quantitative information can be obtained about recollection, reconstruction, and familiarity judgment by defining a Markov model over simple recall tasks like those that are used in clinical neuropsychology batteries. The model measures these processes separately for learning, forgetting, and reminiscence. We implemented this procedure in some developmental experiments, whose aims were (a) to measure age changes in recollective and nonrecollective retrieval during learning, forgetting, and reminiscence and (b) to measure age changes in content dimensions (e.g., taxonomic relatedness) that affect the two forms of retrieval. The model provided excellent fits in all three domains. Concerning (a), recollection, reconstruction, and familiarity judgment all improved during the child-to-adolescent age range in the learning domain, whereas only recollection improved in the forgetting domain, and the processes were age invariant in the reminiscence domain. Concerning (b), although some elements of the adult pattern of taxonomic relatedness effects were detected by early adolescence, the adult pattern differs qualitatively from corresponding patterns in children and adolescents. PMID- 22778492 TI - Icam-1 upregulation in ethanol-induced Fatty murine livers promotes injury and sinusoidal leukocyte adherence after transplantation. AB - Background. Transplantation of ethanol-induced steatotic livers causes increased graft injury. We hypothesized that upregulation of hepatic ICAM-1 after ethanol produces increased leukocyte adherence, resulting in increased generation of reactive oxygen species (ROS) and injury after liver transplantation (LT). Methods. C57BL/6 wildtype (WT) and ICAM-1 knockout (KO) mice were gavaged with ethanol (6 g/kg) or water. LT was then performed into WT recipients. Necrosis and apoptosis, 4-hydroxynonenal (4-HNE) immunostaining, and sinusoidal leukocyte movement by intravital microscopy were assessed. Results. Ethanol gavage of WT mice increased hepatic triglycerides 10-fold compared to water treatment (P < 0.05). ICAM-1 also increased, but ALT was normal. At 8 h after LT of WT grafts, ALT increased 2-fold more with ethanol than water treatment (P < 0.05). Compared to ethanol-treated WT grafts, ALT from ethanol-treated KO grafts was 78% less (P < 0.05). Apoptosis also decreased by 75% (P < 0.05), and 4-HNE staining after LT was also decreased in ethanol-treated KO grafts compared to WT. Intravital microscopy demonstrated a 2-fold decrease in leukocyte adhesion in KO grafts compared to WT grafts. Conclusions. Increased ICAM-1 expression in ethanol treated fatty livers predisposes to leukocyte adherence after LT, which leads to a disturbed microcirculation, oxidative stress and graft injury. PMID- 22778493 TI - Biliary cystadenomas: a case for complete resection. AB - Introduction and Objective. Biliary cystadenoma is a rare benign neoplasm of the liver with less than 200 cases being reported allover the world. We report a series of 13 cases highlighting the radiological findings and problems related to its management. Materials and Methods. Records of thirteen patients who underwent surgery for biliary cystadenomas, between March 2006 and October 2011, were reviewed retrospectively. Results. Majority of the patients were females (11 out of 13), with a median age of 46 (23-65) years. The most frequent symptom was abdominal pain (92%). Seven patients had presented with history of previous surgery for liver lesions. Five patients had presented with recurrence after partial resection for a suspected hydatid cyst and two after surgery for presumed simple liver cyst. Ten of the 13 patients had complete resection of the cyst with enucleation in 3 patients, 2 of whom in addition required T-tube drainage of the bile duct. There has been no recurrence during the follow-up period ranging from 3 months to 5 years. Conclusion. Biliary cystadenoma must be differentiated from other benign cysts. Hepatic resection or cyst enucleation is the recommended treatment option. PMID- 22778494 TI - Overview: Damage resistance of graded ceramic restorative materials. AB - Improving mechanical response of materials is of great interest in a wide range of disciplines, including biomechanics, tribology, geology, optoelectronics, and nanotechnology. It has been long recognized that spatial gradients in surface composition and structure can improve the mechanical integrity of a material. This review surveys recent results of sliding-contact, flexural, and fatigue tests on graded ceramic materials from our laboratories and elsewhere. Although our findings are examined in the context of possible applications for next generation, graded all-ceramic dental restorations, implications of our studies have broad impact on biomedical, civil, structural, and an array of other engineering applications. PMID- 22778495 TI - Mast cells and histamine: do they influence placental vascular network and development in preeclampsia? AB - The physiological course of pregnancy is closely related to adequate development of the placenta. Shallow invasion of trophoblast as well as decreased development of the placental vascular network are both common features of preeclampsia. To better understand the proangiogenic features of mast cells, in this study we aim to identify the potential relationship between the distribution of mast cells within the placenta and vascular network development. MATERIAL AND METHODS: Placentas from preeclampsia-complicated pregnancies (n = 11) and from physiological pregnancies (n = 11) were acquired after cesarean section. The concentration of histamine was measured, and immunohistochemical staining for mast cell tryptase was performed. Morphometric analysis was then performed. RESULTS: We noticed significant differences between the examined groups. Notably, in the preeclampsia group compared to the control group, we observed a higher mean histamine concentration, higher mast cell density (MCD), lower mean mast cell (MMCA) and lower vascular/extravascular (V/EVT) index. In physiological pregnancies, a positive correlation was observed between the histamine concentration and V/VEVT index as well as MCD and the V/VEVT index. In contrast, a negative correlation was observed between MMCA and the V/EVT index in physiological pregnancies. CONCLUSIONS: Based on the data from our study, we suggest that a differential distribution of mast cells and corresponding changes in the concentration of histamine are involved in the defective placental vascularization seen in preeclamptic placentas. PMID- 22778496 TI - Danger signals activating the immune response after trauma. AB - Sterile injury can cause a systemic inflammatory response syndrome (SIRS) that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins) as well as exogenous pathogen-associated molecular patterns (PAMPs) play a crucial role in the initiation of the immune response. With popularization of the "danger theory," numerous DAMPs and PAMPs and their corresponding pathogen-recognition receptors have been identified. In this paper, we highlight the role of the DAMPs high-mobility group box protein 1 (HMGB1), interleukin-1alpha (IL-1alpha), and interleukin-33 (IL-33) as unique dual-function mediators as well as mitochondrial danger signals released upon cellular trauma and necrosis. PMID- 22778498 TI - High-mobility group box 1 induces calcineurin-mediated cell hypertrophy in neonatal rat ventricular myocytes. AB - Cardiac hypertrophy is an independent predictor of cardiovascular morbidity and mortality. In recent years, evidences suggest that high-mobility group box 1 (HMGB1) protein, an inflammatory cytokine, participates in cardiac remodeling; however, the involvement of HMGB1 in the pathogenesis of cardiac hypertrophy remains unknown. The aim of this study was to investigate whether HMGB1 is sufficient to induce cardiomyocyte hypertrophy and to identify the possible mechanisms underlying the hypertrophic response. Cardiomyocytes isolated from 1 day-old Sprague-Dawley rats were treated with recombinant HMGB1, at concentrations ranging from 50 ng/mL to 200 ng/mL. After 24 hours, cardiomyocytes were processed for the evaluation of atrial natriuretic peptide (ANP) and calcineurin A expression. Western blot and real-time RT-PCR was used to detect protein and mRNA expression levels, respectively. The activity of calcineurin was also evaluated using a biochemical enzyme assay. HMGB1 induced cardiomyocyte hypertrophy, characterized by enhanced expression of ANP, and increased protein synthesis. Meanwhile, increased calcineurin activity and calcineurin A protein expression were observed in cardiomyocytes preconditioned with HMGB1. Furthermore, cyclosporin A pretreatment partially inhibited the HMGB1-induced cardiomyocyte hypertrophy. Our findings suggest that HMGB1 leads to cardiac hypertrophy, at least in part through activating calcineurin. PMID- 22778497 TI - Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics. AB - Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance. PMID- 22778500 TI - Calorie restriction with a high-fat diet effectively attenuated inflammatory response and oxidative stress-related markers in obese tissues of the high diet fed rats. AB - Obesity characterized by increased mass of adipose tissue leads to systemic inflammation. Calorie restriction (CR) improves parameters associated with immune response and antioxidant defense. We hypothesized that CR with a high fat diet (HFCR) regulates local and systemic inflammation and oxidative stress damage in a high fat diet induced obesity (HF group). We investigated effect of HFCR on inflammation and oxidative stress-related markers in liver and adipose tissues as well as adipokines in plasma. HFCR lowered liver triglyceride levels, total cholesterol levels, and the plasma leptin/adiponectin ratio to normal levels and improved glucose tolerance. HFCR also improved fatty liver and normalized adipocyte size and morphology. HFCR reduced lipid peroxidation and decreased the expression levels of inducible nitric oxide synthetase, cyclooxygenase-2, NF-E2 related factor, and heme oxygenase-1 in the liver. Moreover, HFCR suppressed the expression levels of C- reactive protein and manganese superoxide dismutase in the adipose tissue in the HF group. These results suggest that HFCR may have beneficial effects on inflammation and oxidative stress as well as lipid profiles in the HF diet induced obesity. Moreover, HFCR may be a good way to increase compliance in obese patients and to prevent obesity induced complications without changes in dietary pattern. PMID- 22778501 TI - Development and application of loop-mediated isothermal amplification assays on rapid detection of various types of staphylococci strains. AB - A loop-mediated isothermal amplification (LAMP) method for rapid detection of various Staphylococcus strains and associated antibiotic resistance determinant had been developed and evaluated in this study. Six primers, including outer primers, inner primers and loop primers, were specially designed for recognizing eight distinct sequences on three targets: 16SrRNA, femA and mecA.. Forty-one reference strains, including various species of gram-negative and -positive isolates, were included in this study to evaluate and optimize LAMP assays. The optimal reaction condition was found to be 65 degrees C for 45 min, with detection limits at 100 fg DNA/tube and 10 CFU/reaction for 16S rRNA, 100 fg DNA/tube and 10 CFU/reaction for femA, 1 pg DNA/tube and 100 CFU/reaction for mecA, respectively. Application of LAMP assays were performed on 118 various types of Staphylococcus isolates, the detection rate of LAMP assays for the 16SrRNA, femA and mecA was 100% (118/118), 98.5% (64/65) and 94.3% (66/70), and the negative predictive value (NPV) was 100%, 98.1% and 92.3% respectively; with a 100% positive predictive value (PPV) for all three targets. In conclusion, LAMP assays were demonstrated to be useful and powerful tools for rapid detection of various Staphylococcus strains, and undoubtedly, the rapidness, technical simplicity, and cost-effectiveness of LAMP assays will demonstrate broad application for bacteriological detection of food-borne Methicillin-resistant Staphylococcus (MRS) isolates. PMID- 22778499 TI - Role of prostaglandins in neuroinflammatory and neurodegenerative diseases. AB - Increasing data demonstrates that inflammation participates in the pathophysiology of neurodegenerative diseases. Among the different inflammatory mediators involved, prostaglandins play an important role. The effects induced by prostaglandins might be mediated by activation of their known receptors or by nonclassical mechanisms. In the present paper, we discuss the evidences that link prostaglandins, as well as the enzymes that produce them, to some neurological diseases. PMID- 22778502 TI - The dental amalgam toxicity fear: a myth or actuality. AB - Amalgam has been used in dentistry since about 150 years and is still being used due to its low cost, ease of application, strength, durability, and bacteriostatic effect. When aesthetics is not a concern it can be used in individuals of all ages, in stress bearing areas, foundation for cast-metal and ceramic restorations and poor oral hygiene conditions. Besides all, it has other advantages like if placed under ideal conditions, it is more durable and long lasting and least technique sensitive of all restorative materials, but, concern has been raised that amalgam causes mercury toxicity. Mercury is found in the earth's crust and is ubiquitous in the environment, so even without amalgam restorations everyone is exposed to small but measurable amount of mercury in blood and urine. Dental amalgam restorations may raise these levels slightly, but this has no practical or clinical significance. The main exposure to mercury from dental amalgam occurs during placement or removal of restoration in the tooth. Once the reaction is complete less amount of mercury is released, and that is far below the current health standard. Though amalgam is capable of producing delayed hypersensitivity reactions in some individuals, if the recommended mercury hygiene procedures are followed the risks of adverse health effects could be minimized. For this review the electronic databases and PubMed were used as data sources and have been evaluated to produce the facts regarding amalgam's safety and toxicity. PMID- 22778504 TI - Bio-efficacy of Dioscorea pentaphylla from Midmid-Western Ghats, India. AB - Antibacterial and antifungal activity of crude extracts of medicinally important and traditionally used yam plant, Dioscorea pentaphylla, from mid-Western Ghats was evaluated against 27 bacterial and 5 fungal clinical strains collected of the patients from infectious sources. The clinical strains belonging to their respective species showed concentration-dependent susceptibility toward crude petroleum ether extract, chloroform extract and methanol extract at 100 MUg/100 MUl. The extracts exhibited predominant antibacterial activity against Staphylococcus aureus (ATCC-20852), Pseudomonas aeruginosa (ATCC-29737) and Klebsiella pneumoniae (MTCC-618), respectively, and five clinically isolated pathogenic fungi, Trichophyton rubrum, Microsporum gypseum, Tricophyton tonsurans, Microsporum audouini, and Candida albicans, with antibacterial drug ciprofloxacin and antifungal drug fluconozole (50 MUg/100 MUl) as standards. Out of the three extracts, ethanol extracts possessed better minimum inhibitory concentration (MIC) against all the bacterial strains. All the three extracts showed significant activity against all the five fungal pathogen strains. The results are promising and support the traditional use of D. pentaphylla for the treatment of bacterial and fungal infections. PMID- 22778503 TI - Do herbal medicines have potential for managing snake bite envenomation? AB - Snake envenomation is a global public health problem, with highest incidence in Southeast Asia. Inadequate health services, difficult transportation and consequent delay in antisnake venom administration are the main reasons for high mortality. Adverse drug reactions and inadequate storage conditions limit the use of antisnake venom. The medicinal plants, available locally and used widely by traditional healers, therefore need attention. A wide array of plants and their active principles have been evaluated for pharmacological properties. However, numerous unexplored plants claimed to be antidotes in folklore medicine need to be studied. The present article reviews the current status of various medicinal plants for the management of snake bite. PMID- 22778505 TI - Safety Profile of a Polyherbal Formulation (Gynocare capsules) in Female Rats by Subchronic Oral Toxicity Study. AB - Gynocare capsules, is a polyherbal formulation, are used as uterine tonic and for treating gynaecological ailments like infertility, leucorrhea, and menstrual disorders. The formulation contains ingredients of herbal origin, such as, extracts of Ashoka, Vasaka, Durva, Chandan, Musk, and so on. It was evaluated for its safety at the therapeutic dose level by a repeated dose oral toxicity study in albino Wistar rats. The herbal formulation was administered orally at a therapeutic dose of 100 mg/kg/day, for 90 days. All animals were monitored daily for their health status and signs of abnormalities. The body weight, water consumption, and food intake were measured once weekly. At the end of the experimental period, various hematological and biochemical parameters were estimated and histopathologies of selected organs were conducted. The study resulted from the long-term oral administration of Gynocare capsules (100 mg/kg), did not cause any relevant signs of toxicity nor significant changes in the physical, hematological and biochemical parameters. However, statistically significant differences were seen in the relative organ weights of adrenal gland, ovary, and serum creatinine levels. The reduction in ovary weight revealed the possibility of the drug targeting the ovary. Moreover, no pathological features were identified in the treated group as monitored by the histopathological analysis of the internal organs. The study established that Gynocare capsules at the dose given (100 mg/kg) did not induce any remarkable or significant toxic effects, indicating that it was safe in rats following oral administration for 90 consecutive days. PMID- 22778506 TI - Hematoxicity of amodiaquine in sprague-dawley rats. AB - OBJECTIVE: The use of amodiaquine (AQ) and its associated toxic effect has been a major public health concern since cases of life-threatening agranulocytosis and hepatic toxicity were reported during its prophylactic use. The objective of this study was to evaluate the hematological safety profile of AQ therapy. MATERIALS AND METHODS: Sprague-Dawley rats were randomly distributed into four groups (n=5). Group 1 was the control, while groups 2, 3, and 4 received AQ treatment for 14 days at varying doses of 5 mg/kgBW, 10 mg/kgBW, and 15 mg/kgBW daily, respectively. RESULTS: Following treatment, hematological variables were comparable in all groups (P>0.05). CONCLUSION: This study provides evidence to support the use of AQ in the treatment of uncomplicated malaria. However, to prevent emergence of local drug resistance, it should be used as part of a combination therapy. Monitoring for adverse effects is suggested. PMID- 22778507 TI - Safety Evaluation of Alcoholic Extract of Boswellia ovalifoliolata Stem-bark in Rats. AB - The safety profile of alcoholic extract of stem-bark of B. ovalifoliolata was investigated in male Wistar albino rats as per OECD guidelines 407. A total of 24 male Wistar rats were divided into four groups of six rats each. Group 1 served as control and was given 0.3% carboxymethylcellulose, groups 2, 3 and 4 were given alcoholic extract of B. ovalifoliolata @ 100, 500 and 1000 mg/kg respectively in 0.3% carboxymethylcellulose orally for 28 days. The animals were observed daily for clinical signs, mortality, physiological and behavioral changes. Body weights were measured at weekly intervals and various hematological parameters like Hb, PCV, TEC, TLC and serum biochemical profile which included AST, ALT, creatine phosphokinase, creatinine, total protein and antioxidant parameters like TBARS and GSH in liver were estimated at the end of experimental period. There were no clinical signs of abnormality. The weekly body weights, organ weights and hematological parameters did not vary significantly amongst the groups. The mean activity of AST, ALT and CPK, and the concentration of serum creatinine, total protein, TBARS and GSH did not differ significantly among the groups. Histological abnormalities of toxicological significance were not detected in groups 2 and 3. However, mild histopathological alterations were observed in higher dose group 4. In conclusion, the present study revealed that the alcoholic extract of stem-bark of B. ovalifoliolata is safe at lower doses of 100 and 500 mg/kg. Hence, alcoholic extract of stem bark of B. ovalifoliolata is safe and no observed adverse effect level (NOAEL) is found to be 500 mg/kg following repeated oral administration for 28 days in rats. PMID- 22778508 TI - Ameliorative Potential of Psidium guajava on Hemato-biochemical Alterations in Arsenic-exposed Wistar Rats. AB - The present study attempts to investigate the effects of Psidium guajava (P. guajava) when administered in combination with sodium arsenite @ 20 ppm in drinking water with the aim of achieving normalization of altered biochemical, hematological parameters suggestive of hepatic damage and depletion of inorganic arsenic following chronic arsenic exposure. Thirty adult Wistar rats were given 20 ppm arsenic for eight weeks along with hydro alcoholic leaf extract of P. guajava at a dose of 100 mg/kg body weight wt. (orally) (once daily for eight weeks). Arsenic exposure led to significant depletion of hemoglobin, red blood cells (RBC) and packed cell volume (PCV) but elevated leucocyte count (TLC). There was a significant increase (P<0.01/P<0.05) in serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphotase (ALP), acid phosphotase (ACP) and blood glucose whereas decrease in total protein level in arsenic-exposed untreated animals. The changes were accompanied by a significant elevation in blood and soft-tissue arsenic concentration. Co administration of P. guajava was most effective not only in reducing arsenic induced hematological and biochemical alterations but also in depleting arsenic from blood and soft tissues following arsenic exposure. We thus recommend combined leaf extract of P. guajava for achieving optimum effects of chelation therapy. PMID- 22778509 TI - Toxicological Evaluation of the Methanol Extract of Gmelina arborea Roxb. Bark in Mice and Rats. AB - OBJECTIVE: The present study was designed to evaluate acute and repeated dose toxicity of the methanol extract (ME) of the Gmelina arborea stem bark. MATERIALS AND METHODS: For the acute toxicity study, ME of G. arborea was orally administered to Swiss albino mice at a dose range of 300-5000 mg/kg. For the repeated dose toxicity study, the Wistar rats of either sex were orally administered with ME of G. arborea at the doses of 300, 1000, and 2000 mg/kg/day for a period of 28 days. The effects on body weight, food and water consumption, organ weight, hematology, clinical chemistry as well as histology were studied. RESULTS: The administration of ME from the G. arborea bark at 300-5000 mg/kg did not produce mortality or significant changes in the clinical signs. The no observed adverse effect level (NOAEL) of ME was 5000 mg/kg. There were no significant differences in the general condition, growth, organ weights, hematological parameters, clinical chemistry values, or gross and microscopic appearance of the organs from the treatment groups as compared to the control group. CONCLUSION: ME of G. arborea was found safe in acute and repeated dose toxicity studies when tested in mice and rats. PMID- 22778510 TI - Repeated Topical Application of para-Phenylenediamine Induces Renal Histopathological Changes in Rats. AB - Hemolytic anemia and rhabdomyolysis have been often reported to be an adverse effect of drug- and chemical-induced toxicity both in experimental and real-life scenario. para-Phenylenediamine (PPD) is a derivative of para-nitroaniline and has been found as an ingredient of almost all hair dye formulations in varying concentrations from 2% to 4% w/v. Earlier studies have reported that the accidental oral ingestion of PPD in humans can lead to acute renal failure because of rhabdomyolysis. In the present investigation, we have tested the chronic topical application of PPD and its effect on the renal histology of Sprague-Dawley rats. The experiment provides clear evidence that topically applied PPD induces hemolytic anemia as evident from the decrease in the total RBC count, packed cell volume, and hemoglobin content apart from rhabdomyolysis which subsequently causes acute renal failure in rats. PMID- 22778511 TI - Studies on apoptotic changes in combined toxicity of citrinin and endosulfan in pregnant wistar rats and their fetuses. AB - BACKGROUND: Citrinin (mycotoxin) and endosulfan (pesticide) both environmental contaminants easily enter the food chain and are caoomon causes of various toxicities. MATERIALS AND METHODS: In the present investigation, citrinin (CIT) (10 mg/kg feed) and endosulfan (1 mg/kg body weight) were administered orally alone and in combination to pregnant Wistar rats from gestational day 6 to 20 to study their effect to cause apoptosis in the pregnant Wistar rats and their fetuses. Apoptosis was assessed in dams by agarose gel electrophoresis, flow cytometry and electron microscopy, while in the fetuses it was assessed by flow cytometry only. RESULT: Citrinin and endosulfan in the combination group caused apoptosis in an additive manner as there was increased number of apoptotic cells as compared to the individual toxin and control groups. The fetuses also showed increased number of apoptotic cells in the combination groups, which also indicated that both the toxins crossed the placental barrier. CONCLUSION: So it was concluded that apoptosis played a significant role in the pathogenesis of endosulfan and citrinin toxicity. PMID- 22778512 TI - Vitamin C Attenuates Chronic Chlorpyrifos-induced Alteration of Neurobehavioral Parameters in Wistar Rats. AB - BACKGROUND: Oxidative stress is one of the molecular mechanisms in chlorpyrifos toxicity. The present study was designed to evaluate the attenuating effect of vitamin C on chlorpyrifos-induced alteration of neurobehavioral performance and the role of muscle acetylchloinesterase (AChE), glycogen and lipoperoxidation in the accomplishment of this task. MATERIALS AND METHODS: Male rats were randomly assigned into 4 groups with the following regimens: soya oil (S/oil), vitamin C (VC), chlorpyrifos (CPF) and vitamin C+CPF (VC+CPF). The regimens were administered by gavage once daily for a period of 17 weeks. Neurobehavioral parameters measuring efficiency of locomotion, motor strength, righting reflex and excitability were evaluated at day 0 (pretreatment value), weeks 8 and 16. The rats were sacrificed at week 17 and evaluated for muscle glycogen and malonaldehyde (MDA) concentrations and AChE activity. RESULTS: The result showed that deficits in locomotion efficiency, motor strength, righting reflex and excitability score induced by chronic CPF were mitigated but not completely abolished by vitamin C. The reduced muscle AChE activity and concentrations of glycogen and MDA evoked by chronic CPF were ameliorated by vitamin C. CONCLUSION: The study therefore showed that improvement in muscle AChE activity, glycogen concentration and reduced lipoperoxidation by vitamin C may be partly responsible for the mitigation of the chronic CPF-induced sensorimotor performance. PMID- 22778513 TI - Lithium affects histogenesis of embryonic chick retina. AB - BACKGROUND: Lithium, a drug used extensively for treatment of bipolar disorders, has also been shown to be neuroprotective in vivo and in vitro. While gross teratogenic effects of lithium at higher doses have been reported, in view of its potential wider use, it is necessary to investigate its effects on tissue formation at relatively low doses of lithium where no apparent teratogenic effects on morphology are observed. MATERIALS AND METHODS: We have used retina of chick embryo to investigate its effects during neural histogenesis. Three major cellular events involved in retinal histogenesis have been monitored: Proliferation as measured by expression of proliferating cell nuclear antigen (PCNA); initiation of differentiation as observed by expression of p27/Kip1 expression; apoptosis as monitored by TdT-mediated dUTPX-nick end labeling. RESULT: We demonstrate that lithium at a dose of 60 mM has no effect on gross eye morphology; it disrupts histogenesis of chick retina by blocking proliferation, inducing apoptosis, and generating post mitotic cells prematurely. PMID- 22778514 TI - Evaluation of protective effect of vitamin e on acrylamide induced testicular toxicity in wister rats. AB - Male wistar rats (weighting 160-180 g) were divided in six groups of 6 animals per group. Group A and F served as control. Groups B, C, D and E received acrylamide at 20 mg/kg body weight for 28 days and groups C and E received additionally vitamin E (50 IU/kg body weight) for 1 to 28 days and 29 - 42(nd) days of experiment, respectively. The animals from groups A, B, and C were sacrificed on day 28(th) of experiment and from groups D, E, and F on 42(nd) day of experiment, respectively. There was significant decrease in the total sperm count and significant increase in the dead sperm count on day 28(th) of study due to acrylamide toxicity. At recovery period, there was significant increase in the total sperm count of vitamin-E-treated group of animals as compared to untreated toxicated rats. But, values were significantly lower than control animals. Microscopically, the lesions in the testes of acrylamide intoxicated rats at 28(th) day revealed destruction of seminiferous tubules at periphery. No spermatid and spermatocytes were seen in the seminiferous tubules. Detachment of spermatogonial cells started at periphery of seminiferous tubules. Atrophy of seminiferous tubules was a constant finding. Some tubules showed vacuolar degenerative changes in germinal epithelium. During the recovery period, destruction of seminiferous tubules, detachment of spermatogonial cells, and atrophy of seminiferous tubules were observed in group D and E. Few sections revealed only spermatogonial cells. At recovery period vitamin-E-treated rats revealed somewhat better architecture of the seminiferous tubules. Late spermatids were seen in few seminiferous tubules and other revealed starting of spermatogenesis. Thus, it appears that Vitamin E is not able to protect testes from acrylamide toxicity during active feeding, but after cessation of acrylamide feeding treatment with vitamin E revealed faster recovery as compare to not treated group. PMID- 22778515 TI - Hematological and Immunological Changes Due to Short-term Oral Administration of Acephate. AB - To evaluate immunotoxicological effects of environmental chemical, subacute toxicity of repeated (28 day) oral administration of acephate (Ace) in BALB/c mice was assessed. Thirty two (sixteen male and sixteen female) mice were divided into four different groups with each group containing eight (four male and four female) mice. Mice of Group C1 were administered normal saline only and served as control. Group T1 was given 1/40(th) of apparent LD(50) (ALD(50)) (8.78 mg/kg), and group T2 was put on 1/30(th) of ALD(50) [11.7 mg/kg], while group T3 received 1/20(th) of ALD(50) [17.55 mg/kg] of Ace suspended in normal saline. The blood samples were collected from mice after 28 days of oral administration and analyzed for hematological, biochemical, and immunological parameters. The study showed that hematological parameters (monocytes and granulocytes) remained unaffected except total leukocyte count and lymphocyte which were decreased highly significantly [P<=0.01] in mice of group T3 on the 28(th) day of experiment. Serum total protein (TP) and serum globulin decreased significantly in mice of treatment groups dose dependently; however, no significant change was seen in serum albumin. Progressive increase in live body weight of mice decreased significantly in extremely toxic group only while spleen:body weight ratio decreased significantly in dose-dependent manner. Furthermore, Ace produced suppressed humoral immune response and the delayed-type hypersensitivity response to Sheep red blood cells (SRBCs) was altered nonsignificantly. The results of this study describe the suppression of immune responses following exposure to Ace at low concentrations in experimental mice. PMID- 22778516 TI - Cardioprotective Activity of Methanol Extract of fruit of Trichosanthes cucumerina on Doxorubicin-induced Cardiotoxicity in Wistar Rats. AB - AIM AND OBJECTIVE: The objective was to determine the activity of methanol extract of fruit of Trichosanthes cucumerina in doxorubicin-induced cardiotoxicity in rats. MATERIALS AND METHODS: The methanol extract of fruit of T. cucumerina was prepared. Male Wistar rats were divided in four groups. Group I was vehicle control. Group II animals received doxorubicin 4 mg/kg i.p. on days 21, 28, 35, and 42. Group III and IV animals were treated with methanol extract of T. cucumerina (500 and 1000 mg/kg, respectively) for 49 days. Doxorubicin was administered on days 21, 28, 35, and 42 days. The parameters of study were body weight, serum biomarkers, ECG, blood pressure, and left ventricular function. At the end of the study, the histology of heart, liver, and kidney was carried out. RESULTS: Cardiac toxicity by doxorubicin was manifested as body weight loss, elevated serum LDH and CK-MB, increased ST, QT and QRS complex, reduced blood pressure, and left ventricular function. The methanol extract of T. cucumerina significantly decreased LDH and CK-MB, reduced ST, QT interval and QRS complex, increased heart rate, restored blood pressure, and left ventricular function. Doxorubicin caused liver and kidney necrosis, cellular infiltration, and vascular changes that indicated injury. CONCLUSION: T. cucumerina (1000 mg/kg) reduced the severity of doxorubicin-induced cardiac damage especially in heart. It is concluded that doxorubicin-induced cardiotoxicity is reduced by pretreatment with methanol extract of fruit of T. cucumerina. PMID- 22778517 TI - Cold stress offered modulation on chlorpyrifos toxicity in aging rat central nervous system. AB - The adverse effects produced by chlorpyrifos (CPF) or cold stress alone in humans and animals are well documented, but there is no information available relating to the consequences of their co- exposure in an age-related manner. In this study, effects of sublethal doses of CPF were carried out in vivo, for 48 h to assess the biochemical perturbations in relation to interactions with cold stress (15 degrees C and 20 degrees C) in different age group rat CNS. A positive interaction of CPF with age of animal and cold exposure was observed resulting in marked decrease in the activity levels of AChE (P<0.05), ChAT (P<0.05), Na(+), K(+)-ATPase (P<0.05), Ca(2+)-ATPase (P<0.05), and Mg(2+)-ATPase (P<0.05). The ANOVA and posthoc analysis showed that regulatory enzymes decreased significantly (P<0.05) on CPF exposure. Overall, the effect of co-exposure was appreciably different from either of the exposures. Synergistic interaction of CPF and cold stress at 15 degrees C showed higher inhibition in comparison with CPF and cold stress alone and together at 20 degrees C. Further, this study reveals that young animals are significantly vulnerable and sensitive than adults. PMID- 22778518 TI - To Study the Effect of Vitamin D and E on Sodium-Fluoride-induced Toxicity in Reproductive Functions of Male Rabbits. AB - OBJECTIVES: Fluorosis is an endemic problem in many countries of world. This study was designed to see the effect of fluoride on the reproductive system and to see the role if any of vitamin D or E supplementation on it. MATERIALS AND METHODS: Sixty rabbits were divided into six equal groups. Group I was fed on standard diet, Group II vehicle treated control, Group III on sodium fluoride (NaF) 20 mg/kg body weight, Group IV on NaF + Vitamin D, Group V on NaF + vitamin E, and Group VI on NaF + vitamin D + vitamin E. RESULTS: In Group III (fed on sodium fluoride) significant decrease in sperm count (P<0.001), motility (P<0.001), progressive motility (P<0.01), and epididymal weight (P<0.05) compared to control was seen that was also evident on testicular histology. With vitamin D supplementation, there was a significant improvement in the sperm count (P<0.001), motility (P<0.01), and progressive motility (P<0.05) but remained significantly lower than the control values. With vitamin E supplementation there was significant improvement in the sperm count near normal. With vitamin D and E combined supplementation there was significant improvement in both sperm count and motility near to normal. CONCLUSIONS: We conclude that combined vitamin D and E treatment showed a significant improvement in reproductive functions affected by fluoride. PMID- 22778519 TI - Arsenic Hyper-tolerance in Four Microbacterium Species Isolated from Soil Contaminated with Textile Effluent. AB - Arsenic-contaminated areas of Sanganer, Jaipur, Rajasthan, India were surveyed for the presence of metal resistant bacteria contaminated with textile effluent. Samples were collected from soil receiving regular effluent from the textile industries located at Sanganer area. The properties like pH, electrical conductivity, organic carbon, organic matter, exchangeable calcium, water holding capacity and metals like arsenic, iron, magnesium, lead and zinc were estimated in the contaminated soil. In total, nine bacterial strains were isolated which exhibited minimum inhibitory concentration (MIC) of arsenic ranging between 23.09 and 69.2mM. Four out of nine arsenic contaminated soil samples exhibited the presence of arsenite hyper-tolerant bacteria. Four high arsenite tolerant bacteria were characterized by 16S rDNA gene sequencing which revealed their similarity to Microbacterium paraoxydans strain 3109, Microbacterium paraoxydans strain CF36, Microbacterium sp. CQ0110Y, Microbacterium sp. GE1017. The above results were confirmed as per Bergey's Manual of Determinative Bacteriology. All the four Microbacterium strains were found to be resistant to 100MUg/ml concentration of cobalt, nickel, zinc, chromium selenium and stannous and also exhibited variable sensitivity to mercury, cadmium, lead and antimony. These results indicate that the arsenic polluted soil harbors arsenite hyper-tolerant bacteria like Microbacterium which might play a role in bioremediation of the soil. PMID- 22778520 TI - A dynamic human health risk assessment system. AB - An online human health risk assessment system (OHHRAS) has been designed and developed in the form of a prototype database-driven system and made available for the population of India through a website - www.healthriskindia.in. OHHRAS provide the three utilities, that is, health survey, health status, and bio calculators. The first utility health survey is functional on the basis of database being developed dynamically and gives the desired output to the user on the basis of input criteria entered into the system; the second utility health status is providing the output on the basis of dynamic questionnaire and ticked (selected) answers and generates the health status reports based on multiple matches set as per advise of medical experts and the third utility bio calculators are very useful for the scientists/researchers as online statistical analysis tool that gives more accuracy and save the time of user. The whole system and database-driven website has been designed and developed by using the software (mainly are PHP, My-SQL, Deamweaver, C++ etc.) and made available publically through a database-driven website (www.healthriskindia.in), which are very useful for researchers, academia, students, and general masses of all sectors. PMID- 22778521 TI - Imidacloprid and Thiamethoxam Induced Mutations in Internal Transcribed Spacer 2 (ITS2) of Anopheles stephensi. AB - The present article deals with the polymerase chain reaction (PCR)-based genotoxicity evaluation of neonicotinoid pesticides, imidacloprid and thiamethoxam, by using the genome of a mosquito Anopheles stephensi taken as an experimental model. After treatment of the second instar larvae with LC(20) of the pesticides for 24 h, the induced nucleotide sequence variations in the internal transcribed spacer 2 (ITS2) of freshly hatched unfed control and treated individuals was studied from the sequence alignment data and the mutations in the form of insertion, deletion and substitution of bases were recorded. Measurable differences, indicative of the genetic damage due to imidacloprid and thiamethoxam were observed when ITS2 sequences of control and treated individuals were compared. It was found that imidacloprid-treated individual had 8 deletions, 29 insertions, 18 transitions and 33 transversions, whereas thiamethoxam-treated individual had 10 deletions, 8 insertions, 47 transitions and 68 transversions. PMID- 22778522 TI - Rutin Ameliorates Cyclophosphamide-induced Reproductive Toxicity in Male Rats. AB - Cyclophosphamide (CYC) as an anticancer alkylating agent has been known as a male reproductive toxicant. This study was aimed to evaluate the protective effect of rutin (RUT) on CYC-induced reproductive toxicity. Sexually mature Wistar rats (weighing 199 +/- 10 g with five animals in each group) were given CYC (15 mg/kg) and/or RUT (30 mg/kg) twice a week via gavage for 4 weeks. The sperm counts, sperm motility, sperm morphology, daily sperm production (DSP), testicular, and epididymal antioxidant systems: superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione reductase (GR), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and testicular steroidogenic enzymes (3beta-hydroxysteroid dehydrogenase and 17beta-HSD and spermatogenesis marker enzymes (lactate dehydrogenase (LDH), sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP), acid phosphatase (ACP) in the testes, epididymis and seminal vesicles were investigated at the end of the fourth week. By the end of the fourth week, RUT prevented lower sperm counts, sperm motility, DSP, and higher abnormal sperm numbers induced by CYC. In testes, RUT decreased SOD, LDH, and SDH and increased CAT, 3beta-HSD, 17beta-HSD, ALP, and ACP induced by CYC. In epididymis, RUT increased SOD, CAT, GSH, GSH-Px, GR, GST SDH, ALP and ACP and decreased MDA and LDH induced by CYC. In seminal vesicles, marker enzymes were unchanged in rats given CYC alone or in combination with RUT. It appears that RUT ameliorates CYC reproductive toxicity at the investigated dose. PMID- 22778523 TI - Postnatal Exposure to Sodium Arsenite (NaAsO(2)) Induces Long Lasting Effects in Rat Testes. AB - OBJECTIVE: The present study was undertaken to investigate the effects of early postnatal exposure to sodium arsenite (NaAsO(2)) on rat testis. MATERIALS AND METHODS: Wistar rat pups were administered aqueous solution of NaAsO(2,) 1.5 mg/kg body weight (bw) (experimental) and distilled water (control), respectively, by intraperitoneal route (i.p.) from postnatal day (PND) 1 to 14. Testes were collected after 1, 7 and 36 days (at PND 15, 21 and 50) after the treatment period (PND1-14) from the animals and immersion fixed in Bouin's fluid followed by paraffin embedding. Seven micrometer thick serial sections were cut and stained with hematoxylin and eosin for light microscopic observations. At PND 50, morphological features of sperms and their counting was carried out besides processing the perfusion-fixed testes for electron microscopy (EM). RESULTS AND CONCLUSIONS: The observations revealed an altered morphology of the seminiferous tubules (ST) along with degeneration and dissociation of spermatogenic cells in the experimental animals at PND 15, 21 and 50. Also, increased number of sperms with abnormal morphology and decreased sperm count was noted in the experimental animals. These features together with electron microscopic observations of abnormal mitochondria and apoptotic nuclei of spermatogonia and spermatocytes could be indicative of long-lasting adverse effects on the rat testis induced by exposure to As during early postnatal period. PMID- 22778524 TI - A case of acute pancreatitis with occupational exposure to organophosphorus compound. AB - Pesticides have contributed to dramatic increase in the quality and quantity in crop yields. Organophosphates are commonly used as insecticides in agriculture and are potent toxicants. Patients with organophosphorus poisoning may present with subclinical features of acute pancreatitis. Proper biochemical investigation and clinical correlation helps in diagnosis. PMID- 22778525 TI - Diversity in the chiropractic profession: preparing for 2050. AB - As the diversity of the United States (US) population continues to change, concerns about minority health and health disparities grow. Health professions must evolve to meet the needs of the population. The purpose of this editorial is to review current trends in the diversity of chiropractic students, faculty, and practitioners in the United States. This editorial was informed by a search of the literature, to include PubMed, using the terms chiropractic and diversity, minority, and cultural competency. Demographic information for the chiropractic profession was obtained from the National Board of Chiropractic Examiners and The Chronicle of Higher Education. These data were compared to diversity data for medical doctors and the national and state populations from the American Association of Medical Colleges and the US Census, respectively. Surprisingly little has been published in the peer-reviewed literature on the topic of diversity in the chiropractic profession. For the variables available (sex and race), the data show that proportions in the US chiropractic profession do not match the population. State comparisons to associated chiropractic colleges show similar relationships. No reliable data were found on other diversity characteristics, such as gender identity, religion, and socioeconomic status. The chiropractic profession in the United States currently does not represent the national population with regard to sex and race. Leaders in the profession should develop a strategy to better meet the changing demographics of the US population. More attention to recruiting and retaining students, such as underrepresented minorities and women, and establishing improved cultural competency is needed. PMID- 22778526 TI - Manikin-based clinical simulation in chiropractic education. AB - OBJECTIVE: The purpose of this pilot investigation was to describe the development and implementation of simulation exercises and investigate the feasibility, satisfaction, and relative effectiveness of a manikin-based simulation program in chiropractic undergraduate education. METHODS: This investigation consisted of (1) a qualitative review of other simulation environments and evaluation of related simulation literature to develop the educational processes to be used, (2) implementation of simulation scenarios for 95 student interns and their 11 supervising clinicians, and (3) implementation of simulation scenarios in a random sample of 35 1st-year and 24 2nd-year chiropractic students. Assessment of success was based on results from satisfaction and usability questionnaires and perceived achievement of learning outcomes. Anxiety scores were measured for all participants via a visual analog scale. The level of successful integration of 2nd-year basic science material was assessed using a t test comparing test results between students who participated in the pilot and those who did not. RESULTS: Implementation methods were developed on the basis of qualitative investigation. Simulation program feedback from all participants indicated high levels of satisfaction, usability, and perceived achievement of learning outcomes. Anxiety levels among interns differed according to role chosen (F = 8.07, p =.00). Mean difference in course examination scores of students who participated in simulations versus those who did not was 3.25% favoring students who participated (t = 1.28, p =.10). CONCLUSIONS: High levels of student satisfaction and perceived achievement of learning outcomes were consistently achieved. A trend to successful integration of basic science knowledge provides reason for cautious optimism. More research is recommended. PMID- 22778527 TI - Empowering student learning through rubric-referenced self-assessment. AB - PURPOSE: The purpose of this study was to investigate the effect of rubric referenced self-assessment on performance of anatomy assignments in a group of chiropractic students. METHODS: Participants (N = 259) were first-quarter students who were divided into a treatment group (n = 130) and a comparison group (n = 129). The intervention for both groups involved the use of rubrics to complete the first draft of assignments. General feedback was given by the instructor, and then the students had the opportunity to amend the assignments before resubmission (second draft). The treatment group, however, was also asked to perform rubric-referenced self-assessment of their assignments during their second draft. Although the comparison group was also provided with the identical rubrics for the assignments, the students in this group did not perform rubric referenced self-assessment. RESULTS: The results revealed that the students in the treatment group who used a rubric-referenced self-assessment learning tool received statistically significant higher scores than the comparison group, who did not use this rubric-referenced self-assessment tool. CONCLUSION: This study suggests that practicing rubric-referenced self-assessment enhances student performance on assignments. However, educators continue to face the challenge of developing practical and useful rubric tools for student self-assessment. PMID- 22778528 TI - Interprofessional collaboration and turf wars how prevalent are hidden attitudes? AB - PURPOSE: Interprofessional collaboration in health care is believed to enhance patient outcomes. However, where professions have overlapping scopes of practice (eg, chiropractors and physical therapists), "turf wars" can hinder effective collaboration. Deep-rooted beliefs, identified as implicit attitudes, provide a potential explanation. Even with positive explicit attitudes toward a social group, negative stereotypes may be influential. Previous studies on interprofessional attitudes have mostly used qualitative research methodologies. This study used quantitative methods to evaluate explicit and implicit attitudes of physical therapy students toward chiropractic. METHODS: A paper-and-pencil instrument was developed and administered to 49 individuals (students and faculty) associated with a Canadian University master's entry-level physical therapy program after approval by the Research Ethics Board. The instrument evaluated explicit and implicit attitudes toward the chiropractic profession. Implicit attitudes were determined by comparing response times of chiropractic paired with positive versus negative descriptors. RESULTS: Mean time to complete a word association task was significantly longer (t = 4.75, p =.00) when chiropractic was associated with positive rather than negative words. Explicit and implicit attitudes were not correlated (r = 0.13, p =.38). CONCLUSIONS: While little explicit bias existed, individuals associated with a master's entry-level physical therapy program appeared to have a significant negative implicit bias toward chiropractic. PMID- 22778529 TI - Effect of implementing instructional videos in a physical examination course: an alternative paradigm for chiropractic physical examination teaching. AB - OBJECTIVE: This study examined the effect of implementing instructional video in ophthalmic physical examination teaching on chiropractic students' laboratory physical examination skills and written test results. METHODS: Instructional video clips of ophthalmic physical examination, consisting of both standard procedures and common mistakes, were created and used for laboratory teaching. The video clips were also available for student review after class. Students' laboratory skills and written test results were analyzed and compared using one way analysis of variance (ANOVA) and post hoc multiple comparison tests among three study cohorts: the comparison cohort who did not utilize the instructional videos as a tool, the standard video cohort who viewed only the standard procedure of video clips, and the mistake-referenced video cohort who viewed video clips containing both standard procedure and common mistakes. RESULTS: One way ANOVA suggested a significant difference of lab results among the three cohorts. Post hoc multiple comparisons further revealed that the mean scores of both video cohorts were significantly higher than that of the comparison cohort (p < .001). There was, however, no significant difference of the mean scores between the two video cohorts (p > .05). However, the percentage of students having a perfect score was the highest in the mistake-referenced video cohort. There was no significant difference of written test scores among all three cohorts (p > .05). CONCLUSION: The instructional video of the standard procedure improves chiropractic students' ophthalmic physical examination skills, which may be further enhanced by implementing a mistake-referenced instructional video. PMID- 22778530 TI - A comparative analysis of sonographic interpretation of peripheral nerves in the anterior compartment of the forearm between an experienced and novice interpreter. AB - PURPOSE: This article describes a pilot study that compares the ability of a novice interpreter and an experienced interpreter to interpret ultrasound images of peripheral nerves in the anterior compartment of the forearm. METHODS: Twenty subjects between 18 and 50 years of age were included. A student was taken through tutorials in which she was guided through identification of the peripheral nerves of the anterior forearm. After the tutorials, the experienced interpreter traced the subjects' ulnar nerve and artery neurovascular bundle proximally in the anterior compartment of the forearm until just before it separated into the artery and nerve. Here the distance between the median and ulnar nerve was measured by the investigators. The Bland and Altman design and paired t tests were used to compare the agreement between the results of the two investigators. RESULTS: The Bland and Altman analysis reveals that the difference between two sets of measurements (experienced investigator vs. student) is calculated to be 0.08 mm +/- 0.22 mm for the left arm and 0.16 mm +/- 0.43 mm for the right arm. A paired t test revealed that there is no significant difference in the measurements obtained by the two investigators (left arm: p = .12; right arm: p = .10). These results suggest that the measurements of the two investigators may be interchangeable. CONCLUSIONS: This pilot study shows that after tutorials combining dissection and sonographic interpretation, the ability of a novice interpreter to identify ultrasonographic images of peripheral nerves in the anterior compartment of the forearm is comparable to that of an experienced interpreter. PMID- 22778531 TI - Degree of vertical integration between the undergraduate program and clinical internship with respect to cervical and cranial diagnostic and therapeutic procedures taught at the canadian memorial chiropractic college. AB - OBJECTIVE: The purpose of this study was to determine if diagnostic and therapeutic procedures for the cervical and cranial spine taught to students during the undergraduate program at Canadian Memorial Chiropractic College are required to be used during their internship by their supervising clinicians and, if so, to what extent these procedures are used. METHODS: Course manuals and course syllabi from the Applied Chiropractic and Clinical Diagnosis faculty of the undergraduate chiropractic program for the academic year 2009-2010 were consulted and a list of all diagnostic and therapeutic procedures for the cranial and cervical spine was compiled. This survey asked clinicians to indicate if they themselves used or if they required the students they were supervising to use each procedure listed and, if so, to what extent each procedure was used. Demographic information of each clinician was also obtained. RESULTS: In general, most diagnostic procedures of the head and neck were seldom used, with the exception of postural observation and palpation. By contrast, most cervical orthopaedic tests were often used, with the exception of tests for vertigo. Most therapeutic procedures were used frequently with the exception of prone cervical and "muscle" adjustments. CONCLUSION: There was a low degree of vertical integration for cranial procedures as compared to a much higher degree of vertical integration for cervical procedures between the undergraduate and clinical internship programs taught. Vertical integration is an important element of curricular planning and these results may be helpful to aid educators to more appropriately allocate classroom instruction. PMID- 22778532 TI - Formative dialogues in teaching nonthreatening peer coaching. AB - Teaching universities, while claiming to value good teaching, do little to help individual faculty members improve learning in their classrooms. One effective way to help teachers reflect on their teaching and improve their teaching skills is to have a colleague observe and discuss the teaching episode, yet these dialogues seem to be rare. Visits to the classroom, if they occur at all, are usually summative, with little or no discussion, and typically used for the purposes of evaluation. The formative dialogues program, however, provides opportunities for faculty members to request a collegial, nonthreatening observation and discussion of a teaching session. The program is easy to administer and promises to provide opportunities to enhance the learning environment of the health professional classroom. PMID- 22778533 TI - Small-for-gestational-age births in pregnant women with HIV, due to severity of HIV disease, not antiretroviral therapy. AB - OBJECTIVES: To determine rate and factors associated with small-for-gestational age (SGA) births to women with HIV. METHODS: Prospective data were collected from 183 pregnant women with HIV in an urban HIV prenatal clinic, 2000-2011. An SGA birth was defined as less than the 10th or 3rd percentile of birth weight distribution based upon cut points developed using national vital record data. Bivariate analysis utilized chi-squared and t-tests, and multiple logistic regression analyses were used. RESULTS: The prevalence of SGA was 31.2% at the 10th and 12.6% at the 3rd percentile. SGA at the 10th (OR 2.77; 95% CI, 1.28 5.97) and 3rd (OR 3.64; 95% CI, 1.12-11.76) percentiles was associated with cigarette smoking. Women with CD4 count>200 cells/mm3 at the first prenatal visit were less likely to have an SGA birth at the 3rd percentile (OR 0.29; 95% CI, 0.10-0.86). Women taking NNRTI were less likely to have an SGA infant at the 10th (OR 0.28; 95% CI, 0.10-0.75) and 3rd (OR 0.16; 95% CI, 0.03-0.91) percentiles compared to those women on PIs. CONCLUSIONS: In this cohort with high rates of SGA, severity of HIV disease, not ART, was associated with SGA births after adjusting for sociodemographic, medication, and disease severity. PMID- 22778534 TI - Efavirenz conceptions and regimen management in a prospective cohort of women on antiretroviral therapy. AB - Use of the antiretroviral drug efavirenz (EFV) is not recommended by the WHO or South African HIV treatment guidelines during the first trimester of pregnancy due to potential fetal teratogenicity; there is little evidence of how clinicians manage EFV-related fertility concerns. Women on antiretroviral therapy (ART) were enrolled into a prospective cohort in four public clinics in Johannesburg, South Africa. Fertility intentions, ART regimens, and pregnancy testing were routinely assessed during visits. Women reporting that they were trying to conceive while on EFV were referred for regimen changes. Kaplan-Meier estimators were used to assess incidence across ART regimens. From the 822 women with followup visits between August 2009-March 2011, 170 pregnancies were detected during study followup, including 56 EFV conceptions. Pregnancy incidence rates were comparable across EFV, nevirapine, and lopinavir/ritonavir person-years (95% 100/users (P=0.25)); incidence rates on EFV were 18.6 Confidence Interval: 14.2-24.2). Treatment substitution from EFV was made for 57 women, due to pregnancy intentions or actual pregnancy; however, regimen changes were not systematically applied across women. High rates of pregnancy on EFV and inconsistencies in treatment management suggest that clearer guidelines are needed regarding how to manage fertility-related issues in. women on EFV-based regimens. PMID- 22778535 TI - The changing face of HIV in pregnancy in Rhode Island 2004-2009. AB - Meeting the needs of HIV-infected pregnant women requires understanding their backgrounds and potential barriers to care and safe pregnancy. Foreign-born women are more likely to have language, educational, and economic barriers to care, but may be even more likely to choose to keep a pregnancy. Data from HIV-infected pregnant women and their children in Rhode Island were analyzed to identify trends in demographics, viral control, terminations, miscarriages, timing of diagnosis, and adherence to followup. Between January 2004 and December 2009, 76 HIV-infected women became pregnant, with a total of 95 pregnancies. Seventy-nine percent of the women knew their HIV status prior to becoming pregnant. Fifty-four percent of the women were foreign-born and 38 percent of the 16 women who chose to terminate their pregnancies were foreign-born. While the number of HIV infected women becoming pregnant has increased only slightly, the proportion that are foreign-born has been rising, from 41 percent between 2004 and 2005 to 57.5 percent between 2006 and 2009. A growing number of women are having multiple pregnancies after their HIV diagnosis, due to the strength of their desire for childbearing and the perception that HIV is a controllable illness that does not preclude the creation of a family. PMID- 22778536 TI - Incidence of pregnancy after initiation of antiretroviral therapy in South Africa: a retrospective clinical cohort analysis. AB - BACKGROUND: Little is known about rates of incident pregnancy among HIV-positive women initiating highly active antiretroviral therapy (HAART). METHODS: We conducted a retrospective clinical cohort study among therapy-naive women ages 18 45 initiating HAART between 1 April 2004 and 30 September 2009 at an adult HAART clinic in Johannesburg, South Africa. We used Poisson regression to characterize rates and rate ratios of pregnancy. RESULTS: We evaluated 5,996 women who experienced 727 pregnancies during 14,095 person-years at risk. The overall rate of pregnancy was 5.2 per 100 person-years (95% confidence limits [CL] 4.8, 5.5). By six years, cumulative incidence of first pregnancy was 22.9% (95% CL 20.6%, 25.4%); among women ages 18-25 at HAART initiation, cumulative incidence was 52.2% (95% CL 35.0%, 71.8%). The strongest predictor of incidence of pregnancy was age, with women 18-25 having 13.2 times the rate of pregnancy of women ages 40-45 in adjusted analysis. CD4 counts below 100 and worse adherence to HAART were associated with lower rates of incident pregnancy. CONCLUSIONS: Women experience high rates of incident pregnancy after HAART initiation. Understanding which women are most likely to experience pregnancy will help planning and future efforts to understand the implications of pregnancy for response to HAART. PMID- 22778537 TI - Awareness and interest in intrauterine contraceptive device use among HIV positive women in Cape Town, South Africa. AB - OBJECTIVE: To assess awareness of and interest in intrauterine contraceptive device (IUCD) use among HIV-positive women in Cape Town, South Africa. DESIGN: Cross-sectional survey. METHODS: HIV-positive women aged 18 through 45 years presenting for care at a primary health care clinic in Cape Town, South Africa participated in this study. Consented participants completed a staff-administered questionnaire in a private setting. Descriptive statistics were generated. Comparisons between demographic and reproductive health-related variables and IUCD awareness and interest were performed with multiple logistic regression. Analyses for IUCD interest excluded women with prior surgical sterilization. RESULTS: Of 277 HIV-positive women, 37% were aware of the IUCD; awareness was independently associated with greater age (adjusted odds ratio (AOR)=1.15, 95%; confidence interval (CI): 1.10-1.20) and not switching contraceptive methods in the last year (AOR=2.45, 95% CI: 1.03-5.83). Following an IUCD information session, 86% of women (n=206/240) were interested in IUCD use. IUCD interest was inversely associated with age (AOR=0.91, 95% CI: 0.86-0.97) and marginally positively associated with current menstrual bleeding pattern complaints (AOR=2.14, 95% CI: 0.98-4.68). CONCLUSIONS: Despite low levels of method awareness, HIV-positive women in this setting are frequently interested in IUCD use, indicating need for programming to expand method access. PMID- 22778538 TI - Endoscopic-ultrasound-guided tissue sampling facilitates the detection of local recurrence and extra pelvic metastasis in pelvic urologic malignancy. AB - Pelvic lymph node dissection is the gold standard for assessing nodal disease in prostate or bladder cancer and is superior to CT, MRI and PET staging. Endoscopic ultrasound (EUS) provides an alternative, less invasive method of cytohistologic material acquisition, but its performance in pelvic urologic malignancy is unknown. Therefore, our aim was to evaluate the diagnostic accuracy of EUS guided tissue sampling for these malignancies when compared to a composite cytohistologic and surgical gold standard. A median of 3 FNA passes were performed (n = 19 patients) revealing a sensitivity, specificity, PPV and NPV of 94.4% (72-99), 100% (2-100), 100% (80-100) and 50% (1-98) respectively. The perirectal space was the most frequently sampled location irrespective of the primary urological cancer origin. Final diagnosis established by EUS tissue sampling included bladder cancer (n = 1), bladder cancer local recurrence (n = 8), bladder cancer extra pelvic metastases (n = 1), prostate cancer (n = 2), prostate cancer local recurrence (n = 4), prostate cancer extra pelvic metastases (n = 1), testicular cancer extra pelvic metastases (n = 1) and a benign seminal vesicle (n = 1). EUS guided sampling of the gut wall, lymph nodes, or perirectal space yields suitable diagnostic material to establish the presence of primary, local recurrence or extra pelvic metastases of pelvic urologic malignancy. PMID- 22778539 TI - Outcome and complications of colonoscopy: a prospective multicenter study in northern Israel. AB - Background. Colonoscopy for screening the population at an average risk of colorectal cancer (CRC) is recommended by many leading gastrointestinal associations. Objectives. The objective was to assess the quality, complications and acceptance rate of colonoscopy by patients. Methods. We prospectively gathered data from colonoscopies which were performed between October 2003 and September 2006. Patients were asked to return a follow-up form seven days after the procedure. Those who failed to do so were contacted by phone. Results. 6584 patients were included (50.4% males). The average age of subjects was 57.73 (SD 15.22). CRC screening was the main indication in 12.8%. Cecal intubation was achieved in 92% of patients and bowel preparation was good to excellent in 76.2%. The immediate outcome after colonoscopy was good in 99.4%. Perforations occurred in 3 cases-1 in every 2200 colonoscopies. Significant bleeding occurred in 3 cases (treated conservatively). 94.2% of patients agreed to undergo repeat colonoscopy in the future if indicated. Conclusions. The good quality of examinations, coupled with the low risk for complications and the good acceptance by the patients, encourages us to recommend colonoscopy as a primary screening test for CRC in Israel. PMID- 22778540 TI - PBL 2.0: enhancing problem-based learning through increased student participation. AB - PURPOSE: The purpose of this study was to test a new problem-based learning (PBL) method to see if it reinvigorated the learning experience. METHOD: A new PBL format called PBL 2.0, which met for 90 min two times per week, was introduced in 2009 into an 11-week integrated neuroscience course. One hundred second-year medical students, divided into 10 groups of 10, who had completed their first year of medical school using a traditional PBL format, participated in PBL 2.0. Students were prohibited from using computers during the first session. Learning objectives were distributed at the end of the first day to the small groups, and students were assigned to pairs/trios responsible for leading an interactive discussion on specific learning objectives the following day. Student-led 'lectures' were prohibited. All students were responsible for learning all of the learning objectives so that they could participate in their discussions. RESULTS: One hundred and six students were surveyed and 98 submitted answers (92% response). The majority of groups adhered to the new PBL method. Students invested more time preparing the learning objectives. Students indicated that the level of interaction among students increased. The majority of students preferred the new PBL format. CONCLUSIONS: PBL 2.0 was effective in increasing student interaction and promoting increased learning. PMID- 22778541 TI - Design, implementation and evaluation of a community health training program in an integrated problem-based medical curriculum: a fifteen-year experience at the University of Geneva Faculty of Medicine. AB - BACKGROUND: In the literature the need for relevance in medical education and training has been stressed. In the last 40 years medical schools have been challenged to train doctors competent to respond to community health needs. In the mid-90s the University of Geneva Faculty of Medicine introduced an integrated medical curriculum. In this initiative a particular emphasis was put in introducing a 6-year longitudinal and multidisciplinary Community Health Program (CHP). OBJECTIVES: The aims of the present article are to describe the conception, elaboration and implementation of the CHP as well as its evolution over 15 years and the evaluation of its outcomes. METHODS: The CHP was at its origin elaborated by a small group of highly motivated teachers and later on developed by a multi-disciplinary group of primary care physicians, epidemiologists, public health and bio-ethics specialists, occupational health professionals, lawyers and historians. Evaluation of the program outcomes included educational innovations, new developments of the curriculum and interactions between students and the community. RESULTS: The CHP learning objectives and teaching modalities were defined by the multi-disciplinary group in consensus meetings which triggered a collaborative spirit among teachers and facilitated further developments. The evaluation procedures allowed the monitoring of students' satisfaction which remained high over the years, students' active participation which decreased over time and success at certifying exams which was globally as good as in basic life sciences. The evaluation also assessed outcomes such as educational innovations, new developments of the curriculum and interactions between students and the community. CONCLUSION: As suggested in the literature, our experience shows that the students' direct exposure and practice in the community health environment is an effective training approach to broaden students' education by offering them a community perspective of health and disease. PMID- 22778542 TI - Vasoconstriction potency induced by aminoamide local anesthetics correlates with lipid solubility. AB - Aminoamide local anesthetics induce vasoconstriction in vivo and in vitro. The goals of this in vitro study were to investigate the potency of local anesthetic induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency) of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine) were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED(50)) of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED(50)) of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED(50) in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r(2) = 0.9563; P < 0.001). The potency of the vasoconstriction in the endothelium-denuded aorta induced by local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa. PMID- 22778543 TI - Association of polymorphisms in mitofusin-2 gene with type 2 diabetes in Han Chinese. AB - MFN2 and ESRRA are candidate genes involved in the pathogenesis of T2D. Five tag SNPs in MFN2 gene and three in ESRRA gene were selected and genotyped with TaqMan or PCR-RFLP method in stage 1 populations (555 patients with T2D and 649 control subjects) and stage 2 populations (546 patients with T2D versus 419 control subjects) in Han Chinese. And combining our published data, we estimated the interactions between genetic variants in the MFN2, ESRRA, and PGC-1alpha genes on the T2D risk using MDR. rs873458 (G > A) and rs2878677 (C > T) in MFN2 gene were significantly associated with T2D (P = 0.005 and 0.01) in stage 1 populations, and the association of other SNPs with T2D was not found. In stage 2 populations, we further confirmed the association between rs2878677 and T2D (P = 0.01). Combining the two stage populations, the data supported more significant effect of rs873458 and rs2878677 on T2D risk (P = 0.003 and 0.0001). A-C-G-T-C and G-T-C T-C in MFN2 had significant association with T2D (P = 0.007 and 0.009). The present study also provided the evidence that MFN2 had interactions with PGC 1alpha (P < 0.0001) or ESRRA (P < 0.0001). This study suggested a role of MFN2 polymorphism in the risk of T2D; however, further studies are needed. PMID- 22778544 TI - In vivo visualization of heterogeneous intratumoral distribution of hypoxia inducible factor-1alpha activity by the fusion of high-resolution SPECT and morphological imaging tests. AB - PURPOSE: We aimed to clearly visualize heterogeneous distribution of hypoxia inducible factor 1alpha (HIF) activity in tumor tissues in vivo. METHODS: We synthesized of (125)I-IPOS, a (125)I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of (125)I-IPOS in FM3A tumor-bearing mice was evaluated. Then, the intratumoral localization of this probe was observed by autoradiography, and it was compared with histopathological findings. The distribution of (125)I-IPOS in tumors was imaged by a small animal SPECT/CT scanner. The obtained in vivo SPECT-CT fusion images were compared with ex vivo images of excised tumors. Fusion imaging with MRI was also examined. RESULTS: (125)I-IPOS well accumulated in FM3A tumors. The intratumoral distribution of (125)I-IPOS by autoradiography was quite heterogeneous, and it partially overlapped with that of pimonidazole. High-resolution SPECT-CT fusion images successfully demonstrated the heterogeneity of (125)I-IPOS distribution inside tumors. SPECT-MRI fusion images could give more detailed information about the intratumoral distribution of (125)I-IPOS. CONCLUSION: High-resolution SPECT images successfully demonstrated heterogeneous intratumoral distribution of (125)I-IPOS. SPECT-CT fusion images, more favorably SPECT-MRI fusion images, would be useful to understand the features of heterogeneous intratumoral expression of HIF activity in vivo. PMID- 22778545 TI - Design of a 32-channel EEG system for brain control interface applications. AB - This study integrates the hardware circuit design and the development support of the software interface to achieve a 32-channel EEG system for BCI applications. Since the EEG signals of human bodies are generally very weak, in addition to preventing noise interference, it also requires avoiding the waveform distortion as well as waveform offset and so on; therefore, the design of a preamplifier with high common-mode rejection ratio and high signal-to-noise ratio is very important. Moreover, the friction between the electrode pads and the skin as well as the design of dual power supply will generate DC bias which affects the measurement signals. For this reason, this study specially designs an improved single-power AC-coupled circuit, which effectively reduces the DC bias and improves the error caused by the effects of part errors. At the same time, the digital way is applied to design the adjustable amplification and filter function, which can design for different EEG frequency bands. For the analog circuit, a frequency band will be taken out through the filtering circuit and then the digital filtering design will be used to adjust the extracted frequency band for the target frequency band, combining with MATLAB to design man-machine interface for displaying brain wave. Finally the measured signals are compared to the traditional 32-channel EEG signals. In addition to meeting the IFCN standards, the system design also conducted measurement verification in the standard EEG isolation room in order to demonstrate the accuracy and reliability of this system design. PMID- 22778546 TI - Enhancement of recombinant human endostatin on the radiosensitivity of human pulmonary adenocarcinoma A549 cells and its mechanism. AB - We observed the effects of endostar on the radiosensitivity of pulmonary adenocarcinoma A549 cells and found that endostar inhibited A549 cell growth under normoxia and hypoxia in time and dose-dependent manners; the D(0) and D(q) values in control and endostar groups were (1.36 and 1.30) versus (1.019 and 1.015) under normoxia and (1.693 and 1.39) versus (2.453 and 1.026) under hypoxia, respectively; SER was 1.04 under normoxia and 1.22 under hypoxia in endostar group; under normoxia, the apoptosis rates in control, radiotherapy, endostar and combination groups were 15.9 +/- 0.57%, 42.7 +/- 0.37%, 19.9 +/- 0.48%, and 41.5 +/- 0.38%, respectively, with no significant difference between combination and radiotherapy groups; there was significant difference in G(2)/M phase cells between combination and radiotherapy groups (P = 0.028); under hypoxia, the apoptosis rates in the four groups were 16.7 +/- 0.67%, 30.1 +/- 0.95%, 26.7 +/- 0.62%, and 36.3 +/- 0.71%, respectively, with significant difference between combination and radiotherapy groups; G(2)/M phase cells were higher in combination group than radiotherapy group (P = 0.000); G(2)/M phase cells were higher in hypoxic combination group than in normoxic combination group (P = 0.003). Based on these results, we conclude that under hypoxia, endostar can enhance the radiosensitivity of A549 cells through G(2)/M arrest. PMID- 22778547 TI - Antifungal activity of phenyl derivative of pyranocoumarin from Psoralea corylifolia L. seeds by inhibition of acetylation activity of trichothecene 3-o acetyltransferase (Tri101). AB - Antifungal activity of petroleum ether extract of Psoralea corylifolia L. seed, tested against Fusarium sp. namely, Fusarium oxysporum, Fusarium moniliforme, and Fusarium graminearum, was evaluated by agar well diffusion assay. The chromatographic fractionation of the extract yielded a new phenyl derivative of pyranocoumarin (PDP). The structure of the PDP was confirmed using spectroscopic characterization (GC-MS, IR, and NMR), and a molecular mass of m/z 414 [M-2H](+) with molecular formula C(27)H(28)O(4) was obtained. The PDP had a potent antifungal activity with a minimum inhibitory concentration of 1 mg/mL against Fusarium sp. Molecular docking using Grid-Based Ligand Docking with Energetics (GLIDE, Schrodinger) was carried out with the Tri101, trichothecene 3-O acetyltransferase, as target protein to propose a mechanism for the antifungal activity. The ligand PDP showed bifurcated hydrogen bond interaction with active site residues at TYR 413 and a single hydrogen bond interaction at ARG 402 with a docking score -7.19 and glide energy of -45.78 kcal/mol. This indicated a strong binding of the ligand with the trichothecene 3-O-acetyltransferase, preventing as a result the acetylation of the trichothecene mycotoxin and destruction of the "self-defense mechanism" of the Fusarium sp. PMID- 22778548 TI - Role of exogenous nitric oxide donor in treatment of decompensated hemorrhagic shock in normotensive and hypertensive rats. AB - INTRODUCTION: In this study, we investigated the role of exogenous NO donor, sodium nitroprusside (SNP), on hemodynamic responses and survival rate during decompensated hemorrhagic shock in normotensive and hypertensive rat. METHODS: Male wistar rats were divided into normotensive and hypertensive groups (n = 12 each). Then, the animals were subjected to decompensated hemorrhagic shock by withdrawing blood until the mean arterial pressure (MAP) reached to 40 mmHg. After the shock period, the animals were randomly assigned to SNP-treated (0.5 mg/kg) and control groups (n = 6 each). MAP and heart rate (HR) were monitored throughout the experiment and 60 min after the administration of drug. Serum NO concentrations were measured. The survival rate was counted during next 72 h. RESULTS: Infusion of SNP caused no significant changes in MAP and HR in normotensive and hypertensive animals. Hemorrhagic shock increased serum NO concentration and SNP administration reduced serum NO concentration in either normotensive or hypertensive groups. Survival counts during 72 h after experiment did not improve by SNP administration, and there were no significant differences between normotensive and hypertensive groups. CONCLUSION: SNP administration cannot improve hemodynamic responses and survival count during decompensated hemorrhagic shock in normotensive and hypertensive animals. PMID- 22778549 TI - cDNA-SRAP and its application in differential gene expression analysis: a case study in Erianthus arundinaceum. AB - Erianthus arundinaceum is a wild relative species of sugarcane. The aim of this research was to demonstrate the feasibility of cDNA-SRAP for differential gene expression and to explore the molecular mechanism of drought resistance in E. arundinaceum. cDNA-SRAP technique, for the first time, was applied in the analysis of differential gene expression in E. arundinaceum under drought stress. In total, eight differentially expressed genes with length of 185-427 bp were successfully isolated (GenBank Accession numbers: EU071770, EU071772, EU071774, EU071776, EU071777, EU071779, EU071780, and EU071781). Based on their homologies with genes in GenBank, these genes were assumed to encode ribonuclease III, vacuolar protein, ethylene insensitive protein, aerobactin biosynthesis protein, photosystem II protein, glucose transporter, leucine-rich repeat protein, and ammonia monooxygenase. Real-time PCR analysis on the expression profiling of gene (EU071774) encoding ethylene-insensitive protein and gene (EU071781) encoding ammonia monooxygenase revealed that the expression of these two genes was upregulated both by PEG and ABA treatments, suggesting that they may involve in the drought resistance of E. arundinaceum. This study constitutes the first report of genes activated in E. arundinaceum by drought stress and opens up the application of cDNA-SRAP in differential gene expression analysis in E. arundinaceum under certain stress conditions. PMID- 22778550 TI - The osteogenic study of tissue engineering bone with BMP2 and BMP7 gene-modified rat adipose-derived stem cell. AB - To evaluate the feasibility and advantages of constructing a novel tissue engineering bone, using beta-tricalcium phosphate (beta-TCP) and rat adipose derived stem cells (ADSCs), modified with BMP2 and BMP7 by lentivirus. In the present study, ADSCs transfected with Lv-BMP2 and Lv-BMP7, alone or together, were seeded on beta-TCP scaffold and cultured in vitro. Based on the results of DNA assay, alkaline phosphatase (ALP) activity, alizarin red staining and osteogenic marker genes expression analysis, the BMP2 and BMP7 genes cotransfection group exhibited a higher degree of osteogenic differentiation in vitro. To investigate the in vivo osteogenesis of the tissue engineering bone, the ADSCs/beta-TCP constructs were implanted in rat femurs defects for 6 weeks and studied histomorphology and radiography. The results showed that BMP2 and BMP7 genes cotransfection group dramatically enhanced the efficiency of new bone formation than BMP2 group and BMP7 group in vivo. These results demonstrated that it was advantageous to construct tissue engineering bone using ADSCs cotransfected with BMP2 and BMP7 on beta-TCP, providing a potential way for treating bone defects. PMID- 22778551 TI - Nuclear expression of a mitochondrial DNA gene: mitochondrial targeting of allotopically expressed mutant ATP6 in transgenic mice. AB - Nuclear encoding of mitochondrial DNA transgenes followed by mitochondrial targeting of the expressed proteins (allotopic expression; AE) represents a potentially powerful strategy for creating animal models of mtDNA disease. Mice were created that allotopically express either a mutant (A6M) or wildtype (A6W) mt-Atp6 transgene. Compared to non-transgenic controls, A6M mice displayed neuromuscular and motor deficiencies (wire hang, pole, and balance beam analyses; P < 0.05), no locomotor differences (gait analysis; P < 0.05) and enhanced endurance in Rota-Rod evaluations (P < 0.05). A6W mice exhibited inferior muscle strength (wire hang test; P < 0.05), no difference in balance beam footsteps, accelerating Rota-Rod, pole test and gait analyses; (P < 0.05) and superior performance in balance beam time-to-cross and constant velocity Rota-Rod analyses (P < 0.05) in comparison to non-transgenic control mice. Mice of both transgenic lines did not differ from non-transgenic controls in a number of bioenergetic and biochemical tests including measurements of serum lactate and mitochondrial MnSOD protein levels, ATP synthesis rate, and oxygen consumption (P > 0.05). This study illustrates a mouse model capable of circumventing in vivo mitochondrial mutations. Moreover, it provides evidence supporting AE as a tool for mtDNA disease research with implications in development of DNA-based therapeutics. PMID- 22778553 TI - Biological activities of the polysaccharides produced in submerged culture of two edible Pleurotus ostreatus mushrooms. AB - Exopolysaccharides (EPS) and internal (intracellular) polysaccharides (IPS) obtained from the Pleurotus ostreatus M2191 and PBS281009 cultivated using the batch system revealed an average of between 0.1-2 (EPS) and 0.07-1.5 g/L/day (IPS). The carbohydrate analysis revealed that the polysaccharides comprised 87 89% EPS and 68-74% IPS. The investigation of antioxidant activity in vitro revealed a good antioxidant potential, particularly for the IPS and EPS isolated from PBS281009, as proved by the EC(50) value for DPPH, ABTS scavenging activity, reducing power, and iron chelating activity. PMID- 22778552 TI - Yeast and the AIDS virus: the odd couple. AB - Despite being simple eukaryotic organisms, the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have been widely used as a model to study human pathologies and the replication of human, animal, and plant viruses, as well as the function of individual viral proteins. The complete genome of S. cerevisiae was the first of eukaryotic origin to be sequenced and contains about 6,000 genes. More than 75% of the genes have an assigned function, while more than 40% share conserved sequences with known or predicted human genes. This strong homology has allowed the function of human orthologs to be unveiled starting from the data obtained in yeast. RNA plant viruses were the first to be studied in yeast. In this paper, we focus on the use of the yeast model to study the function of the proteins of human immunodeficiency virus type 1 (HIV-1) and the search for its cellular partners. This human retrovirus is the cause of AIDS. The WHO estimates that there are 33.4 million people worldwide living with HIV/AIDS, with 2.7 million new HIV infections per year and 2.0 million annual deaths due to AIDS. Current therapy is able to control the disease but there is no permanent cure or a vaccine. By using yeast, it is possible to dissect the function of some HIV-1 proteins and discover new cellular factors common to this simple cell and humans that may become potential therapeutic targets, leading to a long-lasting treatment for AIDS. PMID- 22778554 TI - Quantitation of pyrrole-imidazole polyamide in rat plasma by high-performance liquid chromatography coupled with UV detection. AB - A simple and robust method using high-performance liquid chromatography with UV detection was developed and validated for the determination of six pyrrole imidazole (PI) polyamides (HN.49, TGF-beta1f, TGF-beta1t, HN.50f, HN.50t, and LOX 1) in rat plasma. After the plasma proteins were precipitated with methanol containing phenacetin as an internal standard, the analytes were separated on a Luna C18 (2) (5 MUm, 4.6 * 150 mm). Calibration curves were linear over the range of 0.5 to 200 MUg/mL for HN.49, 0.25 to 200 MUg/mL for TGF-beta1f, TGF-beta1t, HN.50t, and LOX-1, 1 to 200 MUg/mL for HN.50f in rat plasma. The inter- and intraday precision were below 15%, and the accuracy was within 15% at the quality controls. The validated method was successfully applied to sample analysis for the pharmacokinetic study. PMID- 22778555 TI - Effectiveness of myocardial contrast echocardiography quantitative analysis during adenosine stress versus visual analysis before percutaneous therapy in acute coronary pain: a coronary artery TIMI grading comparing study. AB - The study aim was to compare two different stress echocardiography interpretation techniques based on the correlation with thrombosis in myocardial infarction (TIMI ) flow grading from acute coronary syndrome (ACS) patients. Forty-one patients with suspected ACS were studied before diagnostic coronary angiography with myocardial contrast echocardiography (MCE) at rest and at stress. The correlation of visual interpretation of MCE and TIMI flow grade was significant. The quantitative analysis (myocardial perfusion parameters: A, beta, and A * beta) and TIMI flow grade were significant. MCE visual interpretation and TIMI flow grade had a high degree of agreement, on diagnosing myocardial perfusion abnormality. If one considers TIMI flow grade <3 as abnormal, MCE visual interpretation at rest had 73.1% accuracy with 58.2% sensitivity and 84.2% specificity and at stress had 80.4% accuracy with 76.6% sensitivity and 83.3% specificity. The MCE quantitative analysis has better accuracy with 100% of agreement with different level of TIMI flow grading. MCE quantitative analysis at stress has showed a direct correlation with TIMI flow grade, more significant than the visual interpretation technique. Further studies could measure the clinical relevance of this more objective approach to managing acute coronary syndrome patient before percutaneous coronary intervention (PCI). PMID- 22778556 TI - Identification of HLA-A24-restricted novel T Cell epitope peptides derived from P cadherin and kinesin family member 20A. AB - We here identified human leukocyte antigen-(HLA-)A(*)2402-restricted epitope peptides from Cadherin 3, type 1, P-cadherin (CDH3) and kinesin family member 20A (KIF20A) that were found to be specifically expressed in cancer cells through genome-wide expression profile analysis. CDH3-10-807 peptide and KIF20A-10-66 peptide successfully induced specific CTL clones, and these selectively responded to COS7 cells expressing both HLA-A(*)2402 and respective protein while did not respond to parental cells or COS7 cells expressing either HLA-A(*)2402 or respective protein. Furthermore, CTL clones responded to cancer cells that endogenously express HLA-A(*)2402 and respective protein, suggesting that CDH3-10 807 peptide and KIF20A-10-66 peptide are naturally presented on HLA-A(*)2402 molecule of human cancer cells. Our results demonstrated that CDH3-10-807 peptide and KIF20A-10-66 peptide are novel HLA-A24-restricted tumor-associated antigens and would be applicable for CTL-inducing cancer therapies. PMID- 22778557 TI - Roles of p53 in various biological aspects of hematopoietic stem cells. AB - Hematopoietic stem cells (HSCs) have the capacity to self-renew as well as to differentiate into all blood cell types, and they can reconstitute hematopoiesis in recipients with bone marrow ablation. In addition, transplantation therapy using HSCs is widely performed for the treatment of various incurable diseases such as hematopoietic malignancies and congenital immunodeficiency disorders. For the safe and successful transplantation of HSCs, their genetic and epigenetic integrities need to be maintained properly. Therefore, understanding the molecular mechanisms that respond to various cellular stresses in HSCs is important. The tumor suppressor protein, p53, has been shown to play critical roles in maintenance of "cell integrity" under stress conditions by controlling its target genes that regulate cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. In this paper, we summarize recent reports that describe various biological functions of HSCs and discuss the roles of p53 associated with them. PMID- 22778558 TI - A dietary supplement containing chlorophytum borivilianum and velvet bean improves sleep quality in men and women. AB - BACKGROUND: Impaired sleep quality is commonplace within industrialized societies, as evidenced by the increasing number of prescription sleep aids available. Certain herbal preparations have been suggested to provide a natural benefit to sleep; however, limited controlled data are available documenting this benefit. In the present study we tested the effect of an experimental dietary supplement, containing the active ingredients Chlorophytum borivilianum and Velvet bean, on sleep quality using the Pittsburgh Sleep Quality Index (PSQI). METHODS: Eighteen healthy and active men and women, with evidence of impaired sleep quality, consumed the supplement daily for 28 days. The PSQI was administered before and after the intervention period. As indicators of safety, resting heart rate and blood pressure were measured, and a complete blood count, comprehensive metabolic panel, and lipid panel were determined. RESULTS: Sleep quality was influenced by the supplement, as evidenced by an improvement in every category of the PSQI questionnaire (P < 0.05), with most category scores improving approximately 50% from pre to post intervention. No adverse outcomes were noted with use of the supplement, as indicated by no change in resting heart rate, blood pressure, or any bloodborne parameter. CONCLUSIONS: An investigational dietary supplement containing the active ingredients Chlorophytum borivilianum and Velvet bean improves sleep quality in men and women. Additional placebo controlled trials are needed to corroborate these findings in individuals with self-reported sleeping difficulty. PMID- 22778559 TI - Imaging-based tumor treatment response evaluation: review of conventional, new, and emerging concepts. AB - Tumor response may be assessed readily by the use of Response Evaluation Criteria in Solid Tumor version 1.1. However, the criteria mainly depend on tumor size changes. These criteria do not reflect other morphologic (tumor necrosis, hemorrhage, and cavitation), functional, or metabolic changes that may occur with targeted chemotherapy or even with conventional chemotherapy. The state-of-the art multidetector CT is still playing an important role, by showing high-quality, high-resolution images that are appropriate enough to measure tumor size and its changes. Additional imaging biomarker devices such as dual energy CT, positron emission tomography, MRI including diffusion-weighted MRI shall be more frequently used for tumor response evaluation, because they provide detailed anatomic, and functional or metabolic change information during tumor treatment, particularly during targeted chemotherapy. This review elucidates morphologic and functional or metabolic approaches, and new concepts in the evaluation of tumor response in the era of personalized medicine (targeted chemotherapy). PMID- 22778560 TI - Influence of signal intensity non-uniformity on brain volumetry using an atlas based method. AB - OBJECTIVE: Many studies have reported pre-processing effects for brain volumetry; however, no study has investigated whether non-parametric non-uniform intensity normalization (N3) correction processing results in reduced system dependency when using an atlas-based method. To address this shortcoming, the present study assessed whether N3 correction processing provides reduced system dependency in atlas-based volumetry. MATERIALS AND METHODS: Contiguous sagittal T1-weighted images of the brain were obtained from 21 healthy participants, by using five magnetic resonance protocols. After image preprocessing using the Statistical Parametric Mapping 5 software, we measured the structural volume of the segmented images with the WFU-PickAtlas software. We applied six different bias-correction levels (Regularization 10, Regularization 0.0001, Regularization 0, Regularization 10 with N3, Regularization 0.0001 with N3, and Regularization 0 with N3) to each set of images. The structural volume change ratio (%) was defined as the change ratio (%) = (100 * [measured volume - mean volume of five magnetic resonance protocols] / mean volume of five magnetic resonance protocols) for each bias-correction level. RESULTS: A low change ratio was synonymous with lower system dependency. The results showed that the images with the N3 correction had a lower change ratio compared with those without the N3 correction. CONCLUSION: The present study is the first atlas-based volumetry study to show that the precision of atlas-based volumetry improves when using N3 corrected images. Therefore, correction for signal intensity non-uniformity is strongly advised for multi-scanner or multi-site imaging trials. PMID- 22778561 TI - Differentiation between symptomatic and asymptomatic extraforaminal stenosis in lumbosacral transitional vertebra: role of three-dimensional magnetic resonance lumbosacral radiculography. AB - OBJECTIVE: To investigate the role of lumbosacral radiculography using 3 dimentional (3D) magnetic resonance (MR) rendering for diagnostic information of symptomatic extraforaminal stenosis in lumbosacral transitional vertebra. MATERIALS AND METHODS: The study population consisted of 18 patients with symptomatic (n = 10) and asymptomatic extraforaminal stenosis (n = 8) in lumbosacral transitional vertebra. Each patient underwent 3D coronal fast-field echo sequences with selective water excitation using the principles of the selective excitation technique (Proset imaging). Morphologic changes of the L5 nerve roots at the symptomatic and asymptomatic extraforaminal stenosis were evaluated on 3D MR rendered images of the lumbosacral spine. RESULTS: Ten cases with symptomatic extraforaminal stenosis showed hyperplasia and degenerative osteophytes of the sacral ala and/or osteophytes at the lateral margin of the L5 body. On 3D MR lumbosacral radiculography, indentation of the L5 nerve roots was found in two cases, while swelling of the nerve roots was seen in eight cases at the exiting nerve root. Eight cases with asymptomatic extraforaminal stenosis showed hyperplasia and degenerative osteophytes of the sacral ala and/or osteophytes at the lateral margin of the L5 body. Based on 3D MR lumbosacral radiculography, indentation or swelling of the L5 nerve roots was not found in any cases with asymptomatic extraforaminal stenosis. CONCLUSION: Results from 3D MR lumbosacral radiculography Indicate the indentation or swelling of the L5 nerve root in symptomatic extraforaminal stenosis. Based on these findings, 3D MR radiculography may be helpful in the diagnosis of the symptomatic extraforaminal stenosis with lumbosacral transitional vertebra. PMID- 22778562 TI - In vitro observation of air bubbles during delivery of various detachable aneurysm embolization coils. AB - OBJECTIVE: Device- or technique-related air embolism is a drawback of various neuro-endovascular procedures. Detachable aneurysm embolization coils can be sources of such air bubbles. We therefore assessed the formation of air bubbles during in vitro delivery of various detachable coils. MATERIALS AND METHODS: A closed circuit simulating a typical endovascular coiling procedure was primed with saline solution degassed by a sonification device. Thirty commercially available detachable coils (7 Axium, 4 GDCs, 5 MicroPlex, 7 Target, and 7 Trufill coils) were tested by using the standard coil flushing and delivery techniques suggested by each manufacturer. The emergence of any air bubbles was monitored with a digital microscope and the images were captured to measure total volumes of air bubbles during coil insertion and detachment and after coil pusher removal. RESULTS: Air bubbles were seen during insertion or removal of 23 of 30 coils (76.7%), with volumes ranging from 0 to 23.42 mm(3) (median: 0.16 mm(3)). Air bubbles were observed most frequently after removal of the coil pusher. Significantly larger amounts of air bubbles were observed in Target coils. CONCLUSION: Variable volumes of air bubbles are observed while delivering detachable embolization coils, particularly after removal of the coil pusher and especially with Target coils. PMID- 22778563 TI - Measurement of intra-fraction displacement of the mediastinal metastatic lymph nodes using four-dimensional CT in non-small cell lung cancer. AB - OBJECTIVE: To measure the intra-fraction displacements of the mediastinal metastatic lymph nodes by using four-dimensional CT (4D-CT) in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Twenty-four patients with NSCLC, who were to be treated by using three dimensional conformal radiation therapy (3D CRT), underwent a 4D-CT simulation during free breathing. The mediastinal metastatic lymph nodes were delineated on the CT images of 10 phases of the breath cycle. The lymph nodes were grouped as the upper, middle and lower mediastinal groups depending on the mediastinal regions. The displacements of the center of the lymph node in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were measured. RESULTS: The mean displacements of the center of the mediastinal lymph node in the LR, AP, and SI directions were 2.24 mm, 1.87 mm, and 3.28 mm, respectively. There were statistically significant differences between the displacements in the SI and LR, and the SI and AP directions (p < 0.05). For the middle and lower mediastinal lymph nodes, the displacement difference between the AP and SI was statistically significant (p = 0.005; p = 0.015), while there was no significant difference between the LR and AP directions (p < 0.05). CONCLUSION: The metastatic mediastinal lymph node movements are different in the LR, AP, and SI directions in patients with NSCLC, particularly for the middle and lower mediastinal lymph nodes. The spatial non uniform margins should be considered for the metastatic mediastinal lymph nodes in involved-field radiotherapy. PMID- 22778564 TI - Small submucosal tumors of the stomach: differentiation of gastric schwannoma from gastrointestinal stromal tumor with CT. AB - OBJECTIVE: To identify the CT features that help differentiate gastric schwannomas (GS) from small (5 cm or smaller) gastrointestinal stromal tumors (GIST) and to assess the growth rates of both tumors. MATERIALS AND METHODS: We included 16 small GSs and 56 GISTs located in the stomach. We evaluated the CT features including size, contour, surface pattern, margins, growth pattern, pattern and degree of contrast enhancement, and the presence of intralesional low attenuation area, hemorrhage, calcification, surface dimpling, fistula, perilesional lymph nodes (LNs), invasion to other organs, metastasis, ascites, and peritoneal seeding. We also estimated the tumor volume doubling time. RESULTS: Compared with GISTs, GSs more frequently demonstrated a homogeneous enhancement pattern, exophytic or mixed growth pattern, and the presence of perilesional LNs (each p < 0.05). The intralesional low attenuation area was more common in GISTs than GSs (p < 0.05). Multivariate analyses indicated that a homogeneous enhancement pattern, exophytic or mixed growth pattern, and the presence of perilesional LNs were statistically significant (p < 0.05). Tumor volume doubling times for GSs (mean, 1685.4 days) were significantly longer than that of GISTs (mean, 377.6 days) (p = 0.004). CONCLUSION: Although small GSs and GISTs show similar imaging findings, GSs more frequently show an exophytic or mixed growth pattern, homogeneous enhancement pattern, perilesional LNs and grow slower than GISTs. PMID- 22778565 TI - Spectral CT: preliminary studies in the liver cirrhosis. AB - OBJECTIVE: To investigate the value of spectral CT imaging in the diagnosis and classification of liver cirrhosis during the arterial phase (AP) and portal venous phase (PVP). MATERIALS AND METHODS: Thirty-eight patients with liver cirrhosis (Child-Pugh class A/B/C: n = 10/14/14), and 43 patients with healthy livers, participated in this study. The researchers used abdominal spectral CT imaging during AP and PVP. Iodine concentration, derived from the iodine-based material-decomposition image and the iodine concentration ratio (IC(ratio)) between AP and PVP, were obtained. Statistical analyses {two-sample t test, One factor analysis of variance, and area under the receiver operating characteristic curve (A [z])} were performed. RESULTS: The mean normalized iodine concentration (NIC) (0.5 +/- 0.12) during PVP in the control group was significantly higher than that in the study group (0.4 +/- 0.10 on average, 0.4 +/- 0.08 for Class A, 0.4 +/- 0.15 for Class B, and 0.4 +/- 0.06 for Class C) (All p < 0.05). Within the cirrhotic liver group, the mean NIC for Class C during the AP (0.1 +/- 0.05) was significantly higher than NICs for Classes A (0.1 +/- 0.06) and B (0.1 +/- 0.03) (Both p < 0.05). The IC(ratio) in the study group (0.4 +/- 0.15), especially for Class C (0.5 +/- 0.14), was higher than that in the control group (0.3 +/- 0.15) (p < 0.05).The combination of NIC and IC(ratio) showed high sensitivity and specificity for differentiating healthy liver from cirrhotic liver, especially in Class C cirrhotic liver. CONCLUSION: Spectral CT Provides a quantitative method with which to analyze the cirrhotic liver, and shows the potential value in the classification of liver cirrhosis. PMID- 22778566 TI - Qualitative and quantitative assessment of isotropic ankle magnetic resonance imaging: three-dimensional isotropic intermediate-weighted turbo spin echo versus three-dimensional isotropic fast field echo sequences. AB - OBJECTIVE: To compare the image quality of volume isotropic turbo spin echo acquisition (VISTA) imaging method with that of the three-dimensional (3D) isotropic fast field echo (FFE) imaging method applied for ankle joint imaging. MATERIALS AND METHODS: MR imaging of the ankles of 10 healthy volunteers was performed with VISTA and 3D FFE sequences by using a 3.0 T machine. Two radiologists retrospectively assessed the tissue contrast between fluid and cartilage (F-C), and fluid and the Achilles tendon (F-T) with use of a 4-point scale. For a quantitative analysis, signal-to-noise ratio (SNR) was obtained by imaging phantom, and the contrast ratios (CRs) were calculated between F-T and F C. Statistical analyses for differences in grades of tissue contrast and CRs were performed. RESULTS: VISTA had significantly superior grades in tissue contrast of F-T (p = 0.001). Results of 3D FFE had superior grades in tissue contrast of F-C, but these result were not statistically significant (p = 0.157). VISTA had significantly superior CRs in F-T (p = 0.002), and 3D FFE had superior CRs in F-C (p = 0.003). The SNR of VISTA was higher than that of 3D FFE (49.24 vs. 15.94). CONCLUSION: VISTA demonstrates superior tissue contrast between fluid and the Achiles tendon in terms of quantitative and qualitative analysis, while 3D FFE shows superior tissue contrast between fluid and cartilage in terms of quantitative analysis. PMID- 22778567 TI - Assessment of collagen-induced arthritis using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles: correlation with 18F fluorodeoxyglucose positron emission tomography data. AB - OBJECTIVE: To evaluate the potential and correlation between near-infrared fluorescence (NIRF) imaging using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles (HGC-Cy5.5) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) imaging of collagen-induced arthritis (CIA). MATERIALS AND METHODS: We used 10 CIA and 3 normal mice. Nine days after the injecting collagen twice, microPET imaging was performed 40 minutes after the intravenous injection of 9.3 MBq (18)F-FDG in 200 uL PBS. One day later, NIRF imaging was performed two hours after the intravenous injection of HGC-cy5.5 (5 mg/kg). We assessed the correlation between these two modalities in the knees and ankles of CIA mice. RESULTS: The mean standardized uptake values of (18)F-FDG for knees and ankles were 1.68 +/- 0.76 and 0.79 +/- 0.71, respectively, for CIA mice; and 0.57 +/- 0.17 and 0.54 +/- 0.20 respectively for control mice. From the NIRF images, the total photon counts per 30 mm(2) for knees and ankles were 2.32 +/- 1.54 * 10(5) and 2.75 +/- 1.51 * 10(5), respectively, for CIA mice, and 1.22 +/- 0.27 * 10(5) and 0.88 +/- 0.24 * 10(5), respectively, for control mice. These two modalities showed a moderate correlation for knees (r = 0.604, p = 0.005) and ankles (r = 0.464, p = 0.039). Moreover, both HGC-Cy5.5 (p = 0.002) and (18)F-FDG-PET (p = 0.005) imaging also showed statistically significant differences between CIA and normal mice. CONCLUSION: NIRF imaging using HGC-Cy5.5 was moderately correlated with (18)F-FDG PET imaging in the CIA model. As such, HGC-Cy5.5 imaging can be used for the early detection of rheumatoid arthritis. PMID- 22778568 TI - Differential diagnosis of axillary inflammatory and metastatic lymph nodes in rabbit models by using diffusion-weighted imaging: compared with conventional magnetic resonance imaging. AB - OBJECTIVE: This experiment aims to determine the diagnostic value of diffusion weighted imaging (DWI) in the differentiation of axillary inflammatory lymph nodes from metastatic lymph nodes in rabbit models in comparison with conventional magnetic resonance imaging (MRI). MATERIALS AND METHODS: Conventional MRI and DWI were performed at 4 weeks after successful inoculation into the forty female New Zealand white rabbits' mammary glands. The size-based and signal-intensity-based criteria and the relative apparent diffusion coefficient (rADC) value were compared between the axillary inflammatory lymph nodes and metastatic lymph nodes, with histopathological findings as the reference standard. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the aforementioned criteria and rADC value in differentiating the axillary inflammatory lymph nodes from metastatic lymph nodes. RESULTS: Thirty-two axillary inflammatory lymph nodes and 46 metastatic ones were successfully isolated and taken into pathological analysis. The differences of the aforementioned criteria between the two groups were not statistically significant (p > 0.05). However, the rADC value of the inflammatory lymph nodes (0.9 +/- 0.14) was higher than that of metastatic ones (0.7 +/- 0.18), with significant difference (p = 0.016). When the rADC value was chosen as 0.80, the area under the ROC curve is greater than all other criteria, and the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for differentiating two groups were 86.2%, 79.3%, 81.2%, 84.2%, and 85.6%, respectively. CONCLUSION: Diffusion-weighted imaging is a promising new technique for differentiating axillary inflammatory lymph nodes from metastatic lymph nodes. Compared with routine magnetic resonance sequences, DWI could provide more useful physiological and functional information for diagnosis. PMID- 22778569 TI - Strategies for successful percutaneous revascularization of chronic total occlusion of the femoropopliteal arteries when the antegrade passage of a guide wire fails. AB - OBJECTIVE: To evaluate the efficacy of various strategies for revascularization of chronic total occlusion of femoropopliteal arteries when the guide wire does not pass in an anterograde direction. MATERIALS AND METHODS: Twenty-four patients with totally occluded femoropopliteal arteries (mean occlusion length 13.75 cm; range, 6-22 cm) were treated by using a retrograde approach and two novel catheters. After successful recanalization or reentry, balloon angioplasty followed by stent placement was performed to complete the revascularization. RESULTS: In 16 cases in which to cross the occlusion via intraluminal or subintimal route was failed, we used Frontrunner catheters in five cases and Outback catheters in 11 cases. In eight cases in which to reenter after subintimal passage of the guide wire was failed, we used Outback catheters. Successful recanalization was achieved intraluminally or subintimally in all cases. One perforation occurred during subintimal passage of the guide wire that was controlled by recanalization of another subintimal tract. There were no cases of distal thromboembolism or other complications. CONCLUSION: A retrograde approach and using the Frontrunner and Outback catheters are safe and effective for successful revascularization of chronic total occlusion of femoropopliteal arteries. In particular, they are useful when the initial antegrade attempts at recanalization have failed. PMID- 22778570 TI - Midterm outcomes of open surgical repair compared with thoracic endovascular repair for isolated descending thoracic aortic disease. AB - OBJECTIVE: This study aimed to assess the surgical morbidity and mortality of thoracic endovascular repair (TEVAR) as compared with open surgical repair (OSR) for isolated descending thoracic aortic disease. MATERIALS AND METHODS: From January 1, 2006 through May 31, 2010, a total of 68 patients with isolated descending thoracic aortic disease were retrospectively reviewed for the presence of perioperative complication, 30-day mortality, and clinical success. The patients were divided into two groups (group 1, OSR, n = 40 vs. group 2, TEVAR, n = 28) and these groups were compared for major variables and late outcomes. RESULTS: The mean age was 58 years (group I = 54 vs. group II = 63 years, p = 0.011). Significant perioperative complications occurred in 12 patients: 8 (20%) in group I and 4 (13%) in group II (p = 0.3). There were five 30 day mortalities of which 4 occurred in group I and 1 in group II (p = 0.23). Clinical success (effective aortic remodeling and complete false lumen obliteration or thrombosis) was achieved in 20 patients (71%). Mean Kaplan-Meier survival rate at 1 year was similar for both groups (group 1 = 87% vs. group 2 = 80%, p = 0.65). CONCLUSION: Thoracic endovascular repair for isolated thoracic aortic disease shows comparable results to OSR. However, the potential for endoleak or rupture remains a challenge that needs to be addressed in the future. Therefore, close follow-up study is needed for the evaluation of satisfactory long-term outcomes. PMID- 22778571 TI - Introducer curving technique for the prevention of tilting of transfemoral Gunther Tulip inferior vena cava filter. AB - OBJECTIVE: To determine whether the introducer curving technique is useful in decreasing the degree of tilting of transfemoral Tulip filters. MATERIALS AND METHODS: The study sample group consisted of 108 patients with deep vein thrombosis who were enrolled and planned to undergo thrombolysis, and who accepted transfemoral Tulip filter insertion procedure. The patients were randomly divided into Group C and Group T. The introducer curving technique was Adopted in Group T. The post-implantation filter tilting angle (ACF) was measured in an anteroposterior projection. The retrieval hook adhering to the vascular wall was measured via tangential cavogram during retrieval. RESULTS: The overall average ACF was 5.8 +/- 4.14 degrees. In Group C, the average ACF was 7.1 +/- 4.52 degrees. In Group T, the average ACF was 4.4 +/- 3.20 degrees. The groups displayed a statistically significant difference (t = 3.573, p = 0.001) in ACF. Additionally, the difference of ACF between the left and right approaches turned out to be statistically significant (7.1 +/- 4.59 vs. 5.1 +/- 3.82, t = 2.301, p = 0.023). The proportion of severe tilt (ACF >= 10 degrees ) in Group T was significantly lower than that in Group C (9.3% vs. 24.1%, chi(2) = 4.267, p = 0.039). Between the groups, the difference in the rate of the retrieval hook adhering to the vascular wall was also statistically significant (2.9% vs. 24.2%, chi(2) = 5.030, p = 0.025). CONCLUSION: The introducer curving technique appears to minimize the incidence and extent of transfemoral Tulip filter tilting. PMID- 22778572 TI - Diffuse ependymal dysembryoplastic neuroepithelial tumor causing spinal drop metastases: a case report. AB - Dysembryoplastic neuroepithelial tumors (DNETs) arise mostly in the supratentorial cerebral cortex. A very rare case of intraventricular DNET with diffuse ependymal involvement, which causes spinal drop metastasis, is presented. PMID- 22778573 TI - Spontaneously developed pulmonary arterial intramural hematoma that mimicked thromboembolism. AB - A 65-year-old woman visited our hospital with a complaint of acute onset dyspnea and radiological manifestations of pulmonary thromboembolism. The patient underwent an exploratory surgery to find a whitish-blue colored mass occupying almost the whole lumen of the main pulmonary arteries. Based on the pathological and radiological findings, the patient was diagnosed to have a pulmonary arterial intramural hematoma. Intramural hematomas are usually observed in the walls of the aorta, and we believe that an isolated intramural hematoma in the pulmonary artery has not been described previously. PMID- 22778574 TI - Intracardiac eustachian valve cyst in an adult detected with other cardiac anomalies: usefulness of multidetector CT in diagnosis. AB - We present an unusual case of an intracardiac Eustachian valve cyst observed concurrently with atresia of the coronary sinus ostium, a persistent left superior vena cava (LSVC) and a bicuspid aortic valve. There have been several echocardiographic reports of Eustachian valve cysts; however, there is no report of multidetector computed tomography (MDCT) findings related to a Eustachian valve cyst. Recently, we observed a Eustachian valve cyst diagnosed on MDCT showing a hypodense cyst at the characteristic location of the Eustachian valve (the junction of the right atrium and inferior vena cava). MDCT also demonstrated additional cardiovascular anomalies including atresia of the coronary sinus ostium and a persistent LSVC and bicuspid aortic valve. PMID- 22778575 TI - Acute severe thrombocytopenia following non-ionic low-osmolarity intravenous contrast medium injection. AB - Intravenous contrast medium (ICM) rarely induces anaphylactic reactions, including urticaria, hypotension and respiratory failure. Even the most modern ICM may cause such adverse events. Thrombocytopenia has been reported as an extreme rare consequence of ICM. Here we report on a case of a 72-year-old male patient with a self-limiting severe acute thrombocytopenia following administration of intravenous non-ionic low-osmolarity contrast medium. No such low platelet count has ever been reported. We also present a review of the literature. PMID- 22778576 TI - Retrograde stent placement for coil embolization of a wide-necked posterior inferior cerebellar artery aneurysm. AB - Wide-necked aneurysms of the posterior inferior cerebellar artery (PICA) are infrequently encountered in cerebrovascular practice, and endovascular treatment is difficult or impossible even with the use of several neck remodeling techniques. We present the case of a patient with a wide-necked aneurysm of the PICA, which was treated by the retrograde stenting through the contralateral vertebral artery and vertebrobasilar junction with antegrade coil embolization. PMID- 22778577 TI - Covered bronchial stent insertion to manage airway obstruction with hemoptysis caused by lung cancer. AB - Malignant airway obstruction and hemoptysis are common in lung cancer patients. Recently, airway stent is commonly used to preserve airway in malignant airway obstruction. Hemoptysis can be managed through various methods including conservative treatment, endobronchial tamponade, bronchoscopic intervention, embolization and surgery. In our case studies, we sought to investigate the effectiveness of airway stents for re-opening the airway as well as tamponade effects in four patients with malignant airway obstruction and bleeding caused by tumors or lymph node invasions. PMID- 22778580 TI - Three-dimensional expansion of a dynamic programming method for boundary detection and its application to sequential magnetic resonance imaging (MRI). AB - This study proposes a fast 3D dynamic programming expansion to find a shortest surface in a 3D matrix. This algorithm can detect boundaries in an image sequence. Using phantom image studies with added uniform distributed noise from different SNRs, the unsigned error of this proposed method is investigated. Comparing the automated results to the gold standard, the best averaged relative unsigned error of the proposed method is 0.77% (SNR = 20 dB), and its corresponding parameter values are reported. We further apply this method to detect the boundary of the real superficial femoral artery (SFA) in MRI sequences without a contrast injection. The manual tracings on the SFA boundaries are performed by well-trained experts to be the gold standard. The comparisons between the manual tracings and automated results are made on 16 MRI sequences (800 total images). The average unsigned error rate is 2.4% (SD = 2.0%). The results demonstrate that the proposed method can perform qualitatively better than the 2D dynamic programming for vessel boundary detection on MRI sequences. PMID- 22778581 TI - Distributed smart device for monitoring, control and management of electric loads in domotic environments. AB - This paper presents a microdevice for monitoring, control and management of electric loads at home. The key idea is to compact the electronic design as much as possible in order to install it inside a Schuko socket. Moreover, the electronic Schuko socket (electronic microdevice + Schuko socket) has the feature of communicating with a central unit and with other microdevices over the existing powerlines. Using the existing power lines, the proposed device can be installed in new buildings or in old ones. The main use of this device is to monitor, control and manage electric loads to save energy and prevent accidents produced by different kind of devices (e.g., iron) used in domestic tasks. The developed smart device is based on a single phase multifunction energy meter manufactured by Analog Devices (ADE7753) to measure the consumption of electrical energy and then to transmit it using a serial interface. To provide current measurement information to the ADE7753, an ultra flat SMD open loop integrated circuit current transducer based on the Hall effect principle manufactured by Lem (FHS-40P/SP600) has been used. Moreover, each smart device has a PL-3120 smart transceiver manufactured by LonWorks to execute the user's program, to communicate with the ADE7753 via serial interface and to transmit information to the central unit via powerline communication. Experimental results show the exactitude of the measurements made using the developed smart device. PMID- 22778582 TI - A high precision position sensor design and its signal processing algorithm for a maglev train. AB - High precision positioning technology for a kind of high speed maglev train with an electromagnetic suspension (EMS) system is studied. At first, the basic structure and functions of the position sensor are introduced and some key techniques to enhance the positioning precision are designed. Then, in order to further improve the positioning signal quality and the fault-tolerant ability of the sensor, a new kind of discrete-time tracking differentiator (TD) is proposed based on nonlinear optimal control theory. This new TD has good filtering and differentiating performances and a small calculation load. It is suitable for real-time signal processing. The stability, convergence property and frequency characteristics of the TD are studied and analyzed thoroughly. The delay constant of the TD is figured out and an effective time delay compensation algorithm is proposed. Based on the TD technology, a filtering process is introduced in to improve the positioning signal waveform when the sensor is under bad working conditions, and a two-sensor switching algorithm is designed to eliminate the positioning errors caused by the joint gaps of the long stator. The effectiveness and stability of the sensor and its signal processing algorithms are proved by the experiments on a test train during a long-term test run. PMID- 22778583 TI - Performance evaluation of fusing protected fingerprint minutiae templates on the decision level. AB - In a biometric authentication system using protected templates, a pseudonymous identifier is the part of a protected template that can be directly compared. Each compared pair of pseudonymous identifiers results in a decision testing whether both identifiers are derived from the same biometric characteristic. Compared to an unprotected system, most existing biometric template protection methods cause to a certain extent degradation in biometric performance. Fusion is therefore a promising way to enhance the biometric performance in template protected biometric systems. Compared to feature level fusion and score level fusion, decision level fusion has not only the least fusion complexity, but also the maximum interoperability across different biometric features, template protection and recognition algorithms, templates formats, and comparison score rules. However, performance improvement via decision level fusion is not obvious. It is influenced by both the dependency and the performance gap among the conducted tests for fusion. We investigate in this paper several fusion scenarios (multi-sample, multi-instance, multi-sensor, multi-algorithm, and their combinations) on the binary decision level, and evaluate their biometric performance and fusion efficiency on a multi-sensor fingerprint database with 71,994 samples. PMID- 22778584 TI - Context-based tourism information filtering with a semantic rule engine. AB - This paper presents the CONCERT framework, a push/filter information consumption paradigm, based on a rule-based semantic contextual information system for tourism. CONCERT suggests a specific insight of the notion of context from a human mobility perspective. It focuses on the particular characteristics and requirements of travellers and addresses the drawbacks found in other approaches. Additionally, CONCERT suggests the use of digital broadcasting as push communication technology, whereby tourism information is disseminated to mobile devices. This information is then automatically filtered by a network of ontologies and offered to tourists on the screen. The results obtained in the experiments carried out show evidence that the information disseminated through digital broadcasting can be manipulated by the network of ontologies, providing contextualized information that produces user satisfaction. PMID- 22778585 TI - Architecture of a framework for providing information services for public transport. AB - This paper presents OnRoute, a framework for developing and running ubiquitous software that provides information services to passengers of public transportation, including payment systems and on-route guidance services. To achieve a high level of interoperability, accessibility and context awareness, OnRoute uses the ubiquitous computing paradigm. To guarantee the quality of the software produced, the reliable software principles used in critical contexts, such as automotive systems, are also considered by the framework. The main components of its architecture (run-time, system services, software components and development discipline) and how they are deployed in the transportation network (stations and vehicles) are described in this paper. Finally, to illustrate the use of OnRoute, the development of a guidance service for travellers is explained. PMID- 22778586 TI - Angular motion estimation using dynamic models in a gyro-free inertial measurement unit. AB - In this paper, we summarize the results of using dynamic models borrowed from tracking theory in describing the time evolution of the state vector to have an estimate of the angular motion in a gyro-free inertial measurement unit (GF-IMU). The GF-IMU is a special type inertial measurement unit (IMU) that uses only a set of accelerometers in inferring the angular motion. Using distributed accelerometers, we get an angular information vector (AIV) composed of angular acceleration and quadratic angular velocity terms. We use a Kalman filter approach to estimate the angular velocity vector since it is not expressed explicitly within the AIV. The bias parameters inherent in the accelerometers measurements' produce a biased AIV and hence the AIV bias parameters are estimated within an augmented state vector. Using dynamic models, the appended bias parameters of the AIV become observable and hence we can have unbiased angular motion estimate. Moreover, a good model is required to extract the maximum amount of information from the observation. Observability analysis is done to determine the conditions for having an observable state space model. For higher grades of accelerometers and under relatively higher sampling frequency, the error of accelerometer measurements is dominated by the noise error. Consequently, simulations are conducted on two models, one has bias parameters appended in the state space model and the other is a reduced model without bias parameters. PMID- 22778587 TI - Nonlinear adaptive PID control for greenhouse environment based on RBF network. AB - This paper presents a hybrid control strategy, combining Radial Basis Function (RBF) network with conventional proportional, integral, and derivative (PID) controllers, for the greenhouse climate control. A model of nonlinear conservation laws of enthalpy and matter between numerous system variables affecting the greenhouse climate is formulated. RBF network is used to tune and identify all PID gain parameters online and adaptively. The presented Neuro-PID control scheme is validated through simulations of set-point tracking and disturbance rejection. We compare the proposed adaptive online tuning method with the offline tuning scheme that employs Genetic Algorithm (GA) to search the optimal gain parameters. The results show that the proposed strategy has good adaptability, strong robustness and real-time performance while achieving satisfactory control performance for the complex and nonlinear greenhouse climate control system, and it may provide a valuable reference to formulate environmental control strategies for actual application in greenhouse production. PMID- 22778588 TI - Redox potential as a means to control the treatment of slurry to lower HS emissions. AB - Slurry can be oxidized to eliminate undesirable emissions, including malodorous hydrogen sulfide (H(2)S). However, it is difficult to assess the optimal amount of oxidizing agent required. In this study, one cow and one pig manure, each in three particle size ranges were oxidized with 0-350 mg ozone/L manure. Redox and H(2)S concentration were measured continuously. During ozonation the manures gave equivalent redox potential curves. A relatively rapid rise in redox potential was observed within a range of -275 mV to -10 mV, with all manures changing as a minimum from -200 mV to -80 mV. The gaseous H(2)S emissions were decreased by 99.5% during the redox increase (-200 mV to -80 mV). This is attributed to H(2)S oxidation by ozone and oxygen, and is not due to H(2)S deprotonation or gas flushing. By identifying the initiation of the final redox level following the rise, the amount of ozone required to remove H(2)S from the manure samples was estimated to be in the range of 6-24 mg O(3)/L manure, depending on the type of manure. Hence, continuous monitoring of redox potential (termination of the redox rise) during the oxidation treatment is a simple method of achieving cost effective minimization of H(2)S emissions from slurry. PMID- 22778589 TI - A framework for supervising lifestyle diseases using long-term activity monitoring. AB - Activity monitoring of a person for a long-term would be helpful for controlling lifestyle associated diseases. Such diseases are often linked with the way a person lives. An unhealthy and irregular standard of living influences the risk of such diseases in the later part of one's life. The symptoms and the initial signs of these diseases are common to the people with irregular lifestyle. In this paper, we propose a novel healthcare framework to manage lifestyle diseases using long-term activity monitoring. The framework recognizes the user's activities with the help of the sensed data in runtime and reports the irregular and unhealthy activity patterns to a doctor and a caregiver. The proposed framework is a hierarchical structure that consists of three modules: activity recognition, activity pattern generation and lifestyle disease prediction. We show that it is possible to assess the possibility of lifestyle diseases from the sensor data. We also show the viability of the proposed framework. PMID- 22778590 TI - Full-scale prestress loss monitoring of damaged RC structures using distributed optical fiber sensing technology. AB - For the safety of prestressed structures, prestress loss is a critical issue that will increase with structural damage, so it is necessary to investigate prestress loss of prestressed structures under different damage scenarios. Unfortunately, to date, no qualified techniques are available due to difficulty for sensors to survive in harsh construction environments of long service life and large span. In this paper, a novel smart steel strand based on the Brillouin optical time domain analysis (BOTDA) sensing technique was designed and manufactured, and then series of tests were used to characterize properties of the smart steel strands. Based on prestress loss principle analysis of damaged structures, laboratory tests of two similar beams with different damages were used to verify the concept of full-scale prestress loss monitoring of damaged reinforced concrete (RC) beams by using the smart steel strands. The prestress losses obtained from the Brillouin sensors are compared with that from conventional sensors, which provided the evolution law of prestress losses of damaged RC beams. The monitoring results from the proposed smart strand can reveal both spatial distribution and time history of prestress losses of damaged RC beams. PMID- 22778591 TI - Fiber sensor systems based on fiber laser and microwave photonic technologies. AB - Fiber-optic sensors, especially fiber Bragg grating (FBG) sensors are very attractive due to their numerous advantages over traditional sensors, such as light weight, high sensitivity, cost-effectiveness, immunity to electromagnetic interference, ease of multiplexing and so on. Therefore, fiber-optic sensors have been intensively studied during the last several decades. Nowadays, with the development of novel fiber technology, more and more newly invented fiber technologies bring better and superior performance to fiber-optic sensing networks. In this paper, the applications of some advanced photonic technologies including fiber lasers and microwave photonic technologies for fiber sensing applications are reviewed. FBG interrogations based on several kinds of fiber lasers, especially the novel Fourier domain mode locking fiber laser, have been introduced; for the application of microwave photonic technology, examples of microwave photonic filtering utilized as a FBG sensing interrogator and microwave signal generation acting as a transversal loading sensor have been given. Both theoretical analysis and experimental demonstrations have been carried out. The comparison of these advanced photonic technologies for the applications of fiber sensing is carried out and important issues related to the applications have been addressed and the suitable and potential application examples have also been discussed in this paper. PMID- 22778592 TI - A long-wavelength fluorescent squarylium cyanine dye possessing boronic acid for sensing monosaccharides and glycoproteins with high enhancement in aqueous solution. AB - Fluorescence sensing of saccharides and glycoproteins using a boronic acid functionalized squarylium cyanine dye ("SQ-BA") is characterized in terms of synthetic, fluorometric, thermodynamic and kinetic parameters. In our previous work, this newly synthesized dye was successfully applied to the separation and quantification of Gram-positive bacteria by capillary electrophoresis with laser induced fluorescence detection (CE-LIF); however, the fundamental properties of the dye and its saccharide complexes still required elucidation, as presented in this paper. The dye itself forms nonemissive, soluble aggregates in aqueous solution. With the addition of a monosaccharide, the dye aggregate dissociates to form an emissive monomer accompanied by the formation of a cyclic cis-diol ester with long-wavelength emission (lambda(ex) = 630 nm, lambda(em) = 660 nm). A very large fluorescence enhancement factor of 18* was observed for the sensing dye as a fructose complex at pH 10, yielding a limit of detection of 10 MUM fructose. The relative order of fluorescence enhancement of SQ-BA with other monosaccharides was found to be: fructose > ribose > arabinose ~ galactose > xylose > mannose > rhamnose > fucose ~ glucose; and apparent affinity constants of 10(2.80), 10(2.08) and 10(0.86) M(-1) were determined for fructose, ribose and glucose, respectively. Formation of the emissive complexes occurred within minutes, proving the kinetics of the sugar-dye interactions to be suitable for on column labeling methods in CE-LIF. Furthermore, the sensing dye was successfully applied to glycoproteins, mucin type I-S and type III, which were detected with high sensitivity in batch aqueous solution as a result of the sugar-selective boronic acid-diol esterification as well as hydrophobic interactions. PMID- 22778593 TI - Classifying the topology of AHL-driven quorum sensing circuits in proteobacterial genomes. AB - Virulence and adaptability of many Gram-negative bacterial species are associated with an N-acylhomoserine lactone (AHL) gene regulation mechanism called quorum sensing (QS). The arrangement of quorum sensing genes is variable throughout bacterial genomes, although there are unifying themes that are common among the various topological arrangements. A bioinformatics survey of 1,403 complete bacterial genomes revealed characteristic gene topologies in 152 genomes that could be classified into 16 topological groups. We developed a concise notation for the patterns and show that the sequences of LuxR regulators and LuxI autoinducer synthase proteins cluster according to the topological patterns. The annotated topologies are deposited online with links to sequences and genome annotations at http://bacteria.itk.ppke.hu/QStopologies/. PMID- 22778594 TI - An electrochemical DNA microbiosensor based on succinimide-modified acrylic microspheres. AB - An electrochemical microbiosensor for DNA has been fabricated based on new acrylic microspheres modified with reactive N-acryloxysuccinimide (NAS) functional groups. Hydrophobic poly(n-butylacrylate-N-acryloxysuccinimide) microspheres were synthesized in an emulsion form with a simple one-step photopolymerization technique. Aminated DNA probe was attached to the succinimde functional group of the acrylic microspheres via covalent bonding. The hybridization of the immobilized DNA probe with the complementary DNA was studied by differential pulse voltametry using anthraquninone-2-sulfonic acid monohydrate sodium salt (AQMS) as the electroactive hybridization label. The influences of many factors such as duration of DNA probe immobilization and hybridization, pH, type of ions, buffer concentrations, ionic strength, operational temperature and non-complementary DNA on the biosensor performance were evaluated. Under optimized conditions, the DNA microbiosensor demonstrated a linear response range to target DNA over a wide concentration range of 1.0 * 10(-16) and 1.0 * 10(-8) M with a lower limit of detection (LOD) of 9.46 * 10(-17) M (R(2) = 0.97). This DNA microbiosensor showed good reproducibility with 2.84% RSD (relative standard deviation) (n = 3). Application of the NAS-modified acrylic microspheres in the construction of DNA microbiosensor had improved the overall analytical performance of the resultant DNA microbiosensor when compared with other reported DNA biosensors using other nano-materials for membranes and microspheres as DNA immobilization matrices. PMID- 22778595 TI - Detection of prostate stem cell antigen expression in human prostate cancer using quantum-dot-based technology. AB - Quantum dots (QDs) are a new class of fluorescent labeling for biological and biomedical applications. In this study, we detected prostate stem cell antigen (PSCA) expression correlated with tumor grade and stage in human prostate cancer by QDs-based immunolabeling and conventional immunohistochemistry (IHC), and evaluated the sensitivity and stability of QDs-based immunolabeling in comparison with IHC. Our data revealed that increasing levels of PSCA expression accompanied advanced tumor grade (QDs labeling, r = 0.732, p < 0.001; IHC, r = 0.683, p < 0.001) and stage (QDs labeling, r = 0.514, p = 0.001; IHC, r = 0.432, p = 0.005), and the similar tendency was detected by the two methods. In addition, by comparison between the two methods, QDs labeling was consistent with IHC in detecting the expression of PSCA in human prostate tissue correlated with different pathological types (K = 0.845, p < 0.001). During the observation time, QDs exhibited superior stability. The intensity of QDs fluorescence remained stable for two weeks (p = 0.083) after conjugation to the PSCA protein, and nearly 93% of positive expression with their fluorescence still could be seen after four weeks. PMID- 22778596 TI - Double-ended calibration of fiber-optic Raman spectra distributed temperature sensing data. AB - Over the past five years, Distributed Temperature Sensing (DTS) along fiber optic cables using Raman backscattering has become an important tool in the environmental sciences. Many environmental applications of DTS demand very accurate temperature measurements, with typical RMSE < 0.1 K. The aim of this paper is to describe and clarify the advantages and disadvantages of double-ended calibration to achieve such accuracy under field conditions. By measuring backscatter from both ends of the fiber optic cable, one can redress the effects of differential attenuation, as caused by bends, splices, and connectors. The methodological principles behind the double-ended calibration are presented, together with a set of practical considerations for field deployment. The results from a field experiment are presented, which show that with double-ended calibration good accuracies can be attained in the field. PMID- 22778597 TI - Localization with a mobile beacon in underwater acoustic sensor networks. AB - Localization is one of the most important issues associated with underwater acoustic sensor networks, especially when sensor nodes are randomly deployed. Given that it is difficult to deploy beacon nodes at predetermined locations, localization schemes with a mobile beacon on the sea surface or along the planned path are inherently convenient, accurate, and energy-efficient. In this paper, we propose a new range-free Localization with a Mobile Beacon (LoMoB). The mobile beacon periodically broadcasts a beacon message containing its location. Sensor nodes are individually localized by passively receiving the beacon messages without inter-node communications. For location estimation, a set of potential locations are obtained as candidates for a node's location and then the node's location is determined through the weighted mean of all the potential locations with the weights computed based on residuals. PMID- 22778598 TI - Personalized health care system with virtual reality rehabilitation and appropriate information for seniors. AB - The concept of the information society is now a common one, as opposed to the industrial society that dominated the economy during the last years. It is assumed that all sectors should have access to information and reap its benefits. Elderly people are, in this respect, a major challenge, due to their lack of interest in technological progress and their lack of knowledge regarding the potential benefits that information society technologies might have on their lives. The Naviga Project (An Open and Adaptable Platform for the Elderly and Persons with Disability to Access the Information Society) is a European effort, whose main goal is to design and develop a technological platform allowing elder people and persons with disability to access the internet and the information society. Naviga also allows the creation of services targeted to social networks, mind training and personalized health care. In this paper we focus on the health care and information services designed on the project, the technological platform developed and details of two representative elements, the virtual reality hand rehabilitation and the health information intelligent system. PMID- 22778599 TI - Hydrogen gas sensors based on semiconductor oxide nanostructures. AB - Recently, the hydrogen gas sensing properties of semiconductor oxide (SMO) nanostructures have been widely investigated. In this article, we provide a comprehensive review of the research progress in the last five years concerning hydrogen gas sensors based on SMO thin film and one-dimensional (1D) nanostructures. The hydrogen sensing mechanism of SMO nanostructures and some critical issues are discussed. Doping, noble metal-decoration, heterojunctions and size reduction have been investigated and proved to be effective methods for improving the sensing performance of SMO thin films and 1D nanostructures. The effect on the hydrogen response of SMO thin films and 1D nanostructures of grain boundary and crystal orientation, as well as the sensor architecture, including electrode size and nanojunctions have also been studied. Finally, we also discuss some challenges for the future applications of SMO nanostructured hydrogen sensors. PMID- 22778600 TI - Palmprint and face multi-modal biometric recognition based on SDA-GSVD and its kernelization. AB - When extracting discriminative features from multimodal data, current methods rarely concern themselves with the data distribution. In this paper, we present an assumption that is consistent with the viewpoint of discrimination, that is, a person's overall biometric data should be regarded as one class in the input space, and his different biometric data can form different Gaussians distributions, i.e., different subclasses. Hence, we propose a novel multimodal feature extraction and recognition approach based on subclass discriminant analysis (SDA). Specifically, one person's different bio-data are treated as different subclasses of one class, and a transformed space is calculated, where the difference among subclasses belonging to different persons is maximized, and the difference within each subclass is minimized. Then, the obtained multimodal features are used for classification. Two solutions are presented to overcome the singularity problem encountered in calculation, which are using PCA preprocessing, and employing the generalized singular value decomposition (GSVD) technique, respectively. Further, we provide nonlinear extensions of SDA based multimodal feature extraction, that is, the feature fusion based on KPCA-SDA and KSDA-GSVD. In KPCA-SDA, we first apply Kernel PCA on each single modal before performing SDA. While in KSDA-GSVD, we directly perform Kernel SDA to fuse multimodal data by applying GSVD to avoid the singular problem. For simplicity two typical types of biometric data are considered in this paper, i.e., palmprint data and face data. Compared with several representative multimodal biometrics recognition methods, experimental results show that our approaches outperform related multimodal recognition methods and KSDA-GSVD achieves the best recognition performance. PMID- 22778601 TI - A novel "reactomics" approach for cancer diagnostics. AB - Non-invasive detection and monitoring of lethal diseases, such as cancer, are considered as effective factors in treatment and survival. We describe a new disease diagnostic approach, denoted "reactomics", based upon reactions between blood sera and an array of vesicles comprising different lipids and polydiacetylene (PDA), a chromatic polymer. We show that reactions between sera and such a lipid/PDA vesicle array produce chromatic patterns which depend both upon the sera composition as well as the specific lipid constituents within the vesicles. The chromatic patterns were processed through machine-learning algorithms, and the bioinformatics analysis could distinguish both between cancer bearing and healthy patients, respectively, as well between two types of cancers. Size-separation and enzymatic digestion experiments indicate that lipoproteins are the primary components in sera which react with the chromatic biomimetic vesicles. This colorimetric reactomics concept is highly generic, robust, and does not require a priori knowledge upon specific disease markers in sera. Therefore, it could be employed as complementary or alternative approach for disease diagnostics. PMID- 22778602 TI - The release of immunosuppressive factor(s) in young males following exercise. AB - It has been shown that a suppressive protein, acting as an immune suppressor, is generated in animals and humans under particular stresses. However, studies related to immunosuppressive factors in response to the stress resulting from acute exercise are limited. This study compares the effects of pre- and post exercise human serum on concanavalin A stimulated lymphocyte proliferation of mice. In the present study, blood samples in eight male undergraduates (age 21 +/ 0.7 years) were taken before and immediately after ten sets of exercise consisting of 15 free and 30 10-kg loaded squat jumps in each set. The suppression of lymphocyte proliferation was analysed with high pressure liquid chromatography. It was noted from the result of gel chromatography columns that the post-exercise values of the suppression of lymphocyte proliferation, in comparison to corresponding pre-exercise values, were generally greater with significant differences observed in 7.5th-9th min post-exercise eluates (P < 0.05). Such findings suggest that intense eccentric type exercise may lead to generation of immunosuppressive factor(s) in young males. PMID- 22778603 TI - Glycopeptide-based antibody detection in multiple sclerosis by surface plasmon resonance. AB - In multiple sclerosis (MS) the gold standard for the diagnosis and prognosis is, up to now, the use of magnetic resonance imaging markers. No alternative simpler assays proven of use, except for cerebrospinal fluid analysis, have been provided in MS diagnosis. Therefore, there is a need to develop non-invasive, sensitive, simple new techniques for the clinical routine. Herein we present the evaluation of the feasibility of a glycopeptide-based biosensor to detect MS specific antibodies in sera using the surface plasmon resonance technology. The previously described glycopeptide antigen CSF114(Glc) has been immobilized on a gold sensor chip and the method has been optimized for real-time specific autoantibody detection directly in sera. A population of 60 healthy blood donors and 61 multiple sclerosis patients has been screened. The receiver operating characteristic (ROC)-based analysis has established the optimal diagnostic cut off value for the method obtaining a sensitivity of 36% and a specificity of 95%. Sample sera have been also screened with a previously validated ELISA. PMID- 22778604 TI - Thermal and optical activation mechanisms of nanospring-based chemiresistors. AB - Chemiresistors (conductometric sensor) were fabricated on the basis of novel nanomaterials--silica nanosprings ALD coated with ZnO. The effects of high temperature and UV illumination on the electronic and gas sensing properties of chemiresistors are reported. For the thermally activated chemiresistors, a discrimination mechanism was developed and an integrated sensor-array for simultaneous real-time resistance scans was built. The integrated sensor response was tested using linear discriminant analysis (LDA). The distinguished electronic signatures of various chemical vapors were obtained at ppm level. It was found that the recovery rate at high temperature drastically increases upon UV illumination. The feasibility study of the activation method by UV illumination at room temperature was conducted. PMID- 22778605 TI - Robust foreground detection: a fusion of masked grey world, probabilistic gradient information and extended conditional random field approach. AB - Foreground detection has been used extensively in many applications such as people counting, traffic monitoring and face recognition. However, most of the existing detectors can only work under limited conditions. This happens because of the inability of the detector to distinguish foreground and background pixels, especially in complex situations. Our aim is to improve the robustness of foreground detection under sudden and gradual illumination change, colour similarity issue, moving background and shadow noise. Since it is hard to achieve robustness using a single model, we have combined several methods into an integrated system. The masked grey world algorithm is introduced to handle sudden illumination change. Colour co-occurrence modelling is then fused with the probabilistic edge-based background modelling. Colour co-occurrence modelling is good in filtering moving background and robust to gradual illumination change, while an edge-based modelling is used for solving a colour similarity problem. Finally, an extended conditional random field approach is used to filter out shadow and afterimage noise. Simulation results show that our algorithm performs better compared to the existing methods, which makes it suitable for higher-level applications. PMID- 22778606 TI - Time-domain fluorescence lifetime imaging techniques suitable for solid-state imaging sensor arrays. AB - We have successfully demonstrated video-rate CMOS single-photon avalanche diode (SPAD)-based cameras for fluorescence lifetime imaging microscopy (FLIM) by applying innovative FLIM algorithms. We also review and compare several time domain techniques and solid-state FLIM systems, and adapt the proposed algorithms for massive CMOS SPAD-based arrays and hardware implementations. The theoretical error equations are derived and their performances are demonstrated on the data obtained from 0.13 MUm CMOS SPAD arrays and the multiple-decay data obtained from scanning PMT systems. In vivo two photon fluorescence lifetime imaging data of FITC-albumin labeled vasculature of a P22 rat carcinosarcoma (BD9 rat window chamber) are used to test how different algorithms perform on bi-decay data. The proposed techniques are capable of producing lifetime images with enough contrast. PMID- 22778607 TI - An early fire detection algorithm using IP cameras. AB - The presence of smoke is the first symptom of fire; therefore to achieve early fire detection, accurate and quick estimation of the presence of smoke is very important. In this paper we propose an algorithm to detect the presence of smoke using video sequences captured by Internet Protocol (IP) cameras, in which important features of smoke, such as color, motion and growth properties are employed. For an efficient smoke detection in the IP camera platform, a detection algorithm must operate directly in the Discrete Cosine Transform (DCT) domain to reduce computational cost, avoiding a complete decoding process required for algorithms that operate in spatial domain. In the proposed algorithm the DCT Inter-transformation technique is used to increase the detection accuracy without inverse DCT operation. In the proposed scheme, firstly the candidate smoke regions are estimated using motion and color smoke properties; next using morphological operations the noise is reduced. Finally the growth properties of the candidate smoke regions are furthermore analyzed through time using the connected component labeling technique. Evaluation results show that a feasible smoke detection method with false negative and false positive error rates approximately equal to 4% and 2%, respectively, is obtained. PMID- 22778608 TI - Using the standard deviation of a region of interest in an image to estimate camera to emitter distance. AB - In this study, a camera to infrared diode (IRED) distance estimation problem was analyzed. The main objective was to define an alternative to measures depth only using the information extracted from pixel grey levels of the IRED image to estimate the distance between the camera and the IRED. In this paper, the standard deviation of the pixel grey level in the region of interest containing the IRED image is proposed as an empirical parameter to define a model for estimating camera to emitter distance. This model includes the camera exposure time, IRED radiant intensity and the distance between the camera and the IRED. An expression for the standard deviation model related to these magnitudes was also derived and calibrated using different images taken under different conditions. From this analysis, we determined the optimum parameters to ensure the best accuracy provided by this alternative. Once the model calibration had been carried out, a differential method to estimate the distance between the camera and the IRED was defined and applied, considering that the camera was aligned with the IRED. The results indicate that this method represents a useful alternative for determining the depth information. PMID- 22778609 TI - Automatic construction of 3D basic-semantic models of inhabited interiors using laser scanners and RFID sensors. AB - This paper is focused on the automatic construction of 3D basic-semantic models of inhabited interiors using laser scanners with the help of RFID technologies. This is an innovative approach, in whose field scarce publications exist. The general strategy consists of carrying out a selective and sequential segmentation from the cloud of points by means of different algorithms which depend on the information that the RFID tags provide. The identification of basic elements of the scene, such as walls, floor, ceiling, windows, doors, tables, chairs and cabinets, and the positioning of their corresponding models can then be calculated. The fusion of both technologies thus allows a simplified 3D semantic indoor model to be obtained. This method has been tested in real scenes under difficult clutter and occlusion conditions, and has yielded promising results. PMID- 22778610 TI - Electric field guided assembly of one-dimensional nanostructures for high performance sensors. AB - Various nanowire or nanotube-based devices have been demonstrated to fulfill the anticipated future demands on sensors. To fabricate such devices, electric field based methods have demonstrated a great potential to integrate one-dimensional nanostructures into various forms. This review paper discusses theoretical and experimental aspects of the working principles, the assembled structures, and the unique functions associated with electric field-based assembly. The challenges and opportunities of the assembly methods are addressed in conjunction with future directions toward high performance sensors. PMID- 22778611 TI - Multisensor system for isotemporal measurements to assess indoor climatic conditions in poultry farms. AB - The rearing of poultry for meat production (broilers) is an agricultural food industry with high relevance to the economy and development of some countries. Periodic episodes of extreme climatic conditions during the summer season can cause high mortality among birds, resulting in economic losses. In this context, ventilation systems within poultry houses play a critical role to ensure appropriate indoor climatic conditions. The objective of this study was to develop a multisensor system to evaluate the design of the ventilation system in broiler houses. A measurement system equipped with three types of sensors: air velocity, temperature and differential pressure was designed and built. The system consisted in a laptop, a data acquisition card, a multiplexor module and a set of 24 air temperature, 24 air velocity and two differential pressure sensors. The system was able to acquire up to a maximum of 128 signals simultaneously at 5 second intervals. The multisensor system was calibrated under laboratory conditions and it was then tested in field tests. Field tests were conducted in a commercial broiler farm under four different pressure and ventilation scenarios in two sections within the building. The calibration curves obtained under laboratory conditions showed similar regression coefficients among temperature, air velocity and pressure sensors and a high goodness fit (R(2) = 0.99) with the reference. Under field test conditions, the multisensor system showed a high number of input signals from different locations with minimum internal delay in acquiring signals. The variation among air velocity sensors was not significant. The developed multisensor system was able to integrate calibrated sensors of temperature, air velocity and differential pressure and operated successfully under different conditions in a mechanically-ventilated broiler farm. This system can be used to obtain quasi-instantaneous fields of the air velocity and temperature, as well as differential pressure maps to assess the design and functioning of ventilation system and as a verification and validation (V&V) system of Computational Fluid Dynamics (CFD) simulations in poultry farms. PMID- 22778612 TI - Magic Ring: a finger-worn device for multiple appliances control using static finger gestures. AB - An ultimate goal for Ubiquitous Computing is to enable people to interact with the surrounding electrical devices using their habitual body gestures as they communicate with each other. The feasibility of such an idea is demonstrated through a wearable gestural device named Magic Ring (MR), which is an original compact wireless sensing mote in a ring shape that can recognize various finger gestures. A scenario of wireless multiple appliances control is selected as a case study to evaluate the usability of such a gestural interface. Experiments comparing the MR and a Remote Controller (RC) were performed to evaluate the usability. From the results, only with 10 minutes practice, the proposed paradigm of gestural-based control can achieve a performance of completing about six tasks per minute, which is in the same level of the RC-based method. PMID- 22778613 TI - Detection of (in)activity periods in human body motion using inertial sensors: a comparative study. AB - Determination of (in)activity periods when monitoring human body motion is a mandatory preprocessing step in all human inertial navigation and position analysis applications. Distinction of (in)activity needs to be established in order to allow the system to recompute the calibration parameters of the inertial sensors as well as the Zero Velocity Updates (ZUPT) of inertial navigation. The periodical recomputation of these parameters allows the application to maintain a constant degree of precision. This work presents a comparative study among different well known inertial magnitude-based detectors and proposes a new approach by applying spectrum-based detectors and memory-based detectors. A robust statistical comparison is carried out by the use of an accelerometer and angular rate signal synthesizer that mimics the output of accelerometers and gyroscopes when subjects are performing basic activities of daily life. Theoretical results are verified by testing the algorithms over signals gathered using an Inertial Measurement Unit (IMU). Detection accuracy rates of up to 97% are achieved. PMID- 22778614 TI - Low-overhead accrual failure detector. AB - Failure detectors are one of the fundamental components for building a distributed system with high availability. In order to maintain the efficiency and scalability of failure detection in a complicated large-scale distributed system, accrual failure detectors that can adapt to multiple applications have been studied extensively. In this paper, an new accrual failure detector--LA-FD with low system overhead has been proposed specifically for current mobile network equipment on the Internet whose processing power, memory space and power supply are all constrained. It does not rely on the probability distribution of message transmission time, or on the maintenance of a history message window. By simple calculation, LA-FD provides adaptive failure detection service with high accuracy to multiple upper applications. The related experiments and results have also been presented. PMID- 22778615 TI - An automated inner dimensional measurement system based on a laser displacement sensor for long-stepped pipes. AB - A novel measurement prototype based on a mobile vehicle that carries a laser scanning sensor is proposed. The prototype is intended for the automated measurement of the interior 3D geometry of large-diameter long-stepped pipes. The laser displacement sensor, which has a small measurement range, is mounted on an extended arm of known length. It is scanned to improve the measurement accuracy for large-sized pipes. A fixing mechanism based on two sections is designed to ensure that the stepped pipe is concentric with the axis of rotation of the system. Data are acquired in a cylindrical coordinate system and fitted in a circle to determine diameter. Systematic errors covering arm length, tilt, and offset errors are analyzed and calibrated. The proposed system is applied to sample parts and the results are discussed to verify its effectiveness. This technique measures a diameter of 600 mm with an uncertainty of 0.02 mm at a 95% confidence probability. A repeatability test is performed to examine precision, which is 1.1 MUm. A laser tracker is used to verify the measurement accuracy of the system, which is evaluated as 9 MUm within a diameter of 600 mm. PMID- 22778616 TI - Calibration and deployment of a fiber-optic sensing system for monitoring debris flows. AB - This work presents a novel fiber-optic sensing system, capable of monitoring debris flows or other natural hazards that produce ground vibrations. The proposed sensing system comprises a demodulator (BraggSCOPE, FS5500), which includes a broadband light source and a data logger, a four-port coupler and four Fiber Bragg Grating (FBG) accelerometers. Based on field tests, the performance of the proposed fiber-optic sensing system is compared with that of a conventional sensing system that includes a geophone or a microphone. Following confirmation of the reliability of the proposed sensing system, the fiber-optic sensing systems are deployed along the Ai-Yu-Zi and Chu-Shui Creeks in Nautou County of central Taiwan for monitoring debris flows. Sensitivity test of the deployed fiber-optic sensing system along the creek banks is also performed. Analysis results of the seismic data recorded by the systems reveal in detail the frequency characteristics of the artificially generated ground vibrations. Results of this study demonstrate that the proposed fiber-optic sensing system is highly promising for use in monitoring natural disasters that generate ground vibrations. PMID- 22778617 TI - EBDC: an energy-balanced data collection mechanism using a mobile data collector in WSNs. AB - The data collection problem is one of the most important issues in Wireless Sensor Networks (WSNs). Constructing a tree from all sensor nodes to the sink node is the simplest way, but this raises the problem of energy unbalance since the sensors closer to the sink node would have much higher workloads from relaying data. To cope with the energy unbalance problem, a number of mobile-sink mechanisms have been proposed in recent years. This paper proposes an Energy Balanced Data Collection mechanism, called EBDC, which determines the trajectory of a mobile data collector (or mobile sink) such that the data-relaying workloads of all sensors can be totally balanced. Theoretical analysis and performance evaluation reveal that the proposed EBDC mechanism outperforms the existing approaches in terms of network lifetime and the degree of energy balancing. PMID- 22778618 TI - Improved image fusion method based on NSCT and accelerated NMF. AB - In order to improve algorithm efficiency and performance, a technique for image fusion based on the Non-subsampled Contourlet Transform (NSCT) domain and an Accelerated Non-negative Matrix Factorization (ANMF)-based algorithm is proposed in this paper. Firstly, the registered source images are decomposed in multi scale and multi-direction using the NSCT method. Then, the ANMF algorithm is executed on low-frequency sub-images to get the low-pass coefficients. The low frequency fused image can be generated faster in that the update rules for W and H are optimized and less iterations are needed. In addition, the Neighborhood Homogeneous Measurement (NHM) rule is performed on the high-frequency part to achieve the band-pass coefficients. Finally, the ultimate fused image is obtained by integrating all sub-images with the inverse NSCT. The simulated experiments prove that our method indeed promotes performance when compared to PCA, NSCT based, NMF-based and weighted NMF-based algorithms. PMID- 22778619 TI - A wide dynamics and fast scan interrogating method for a fiber Bragg grating sensor network implemented using code division multiple access. AB - We propose and demonstrate a fiber Bragg grating (FBG) sensor network employing the code division multiple access (CDMA) technique to identify information from individual sensors. To detect information without considering time delays between sensors, a sliding correlation method is applied, in which two different signals with the same pseudo-random binary sequence (PRBS) pattern, but slightly different frequencies, are applied to the source and detector sides. Moreover, for time domain detection, a wavelength-to-time conversion technique using a wavelength dispersive medium is introduced. The experimental results show that the proposed sensor network has a wide strain dynamic range of 2,400 MUepsilon and a low crosstalk of 950:1. PMID- 22778620 TI - Calcium oxide matrices and carbon dioxide sensors. AB - Homogeneous matrices of calcium oxide (CaO) were prepared by mixing this material with polyethylene glycol (PEG) acting as malleable inert support in order to obtain processable composites. Preliminary tests were carried out to assess the best concentration of CaO in the composite, individuated in the CaO/PEG weight ratio of 1/4. Experimental data highlighted that the composite was able to selectively detect carbon dioxide (CO(2)) via a nanogravimetric method by performing the experiments inside an atmosphere-controlled chamber filled with CO(2). Furthermore, the composite material showed a linear absorption of CO(2) as a function of the gas concentration inside the atmosphere-controlled chamber, thus paving the way for the possible use of these matrices for applications in the field of sensor devices for long-term evaluation of accumulated environmental CO(2). PMID- 22778621 TI - An alternative approach to control measurements of crane rails. AB - Horizontal and vertical positions of points for the control assessment of crane rails are classically determined separately. The procedure is time consuming and causes non-homogenous accuracy of the horizontal and vertical position of control points. The proposed alternative approach is based on polar measurements using a high accuracy total station instrument and a special platform with two precise surveying prisms fixed on it. Measurements are carried out from a single station thus ensuring a common coordinate system and homogenous accuracy. The position of the characteristic point of a rail is derived from the measured positions of both prisms with known geometry of the platform. The influence of platform non horizontality is defined, along with its elimination procedure. Accuracy assessment is ensured with redundant measurements. Result of the proposed procedure is a numerical and graphical presentation of characteristic points. The control parameters required in international Eurocode standards are easily determined from them. PMID- 22778622 TI - An intelligent diagnosis method for rotating machinery using least squares mapping and a fuzzy neural network. AB - This study proposes a new condition diagnosis method for rotating machinery developed using least squares mapping (LSM) and a fuzzy neural network. The non dimensional symptom parameters (NSPs) in the time domain are defined to reflect the features of the vibration signals measured in each state. A sensitive evaluation method for selecting good symptom parameters using detection index (DI) is also proposed for detecting and distinguishing faults in rotating machinery. In order to raise the diagnosis sensitivity of the symptom parameters the synthetic symptom parameters (SSPs) are obtained by LSM. Moreover, possibility theory and the Dempster & Shafer theory (DST) are used to process the ambiguous relationship between symptoms and fault types. Finally, a sequential diagnosis method, using sequential inference and a fuzzy neural network realized by the partially-linearized neural network (PLNN), is also proposed, by which the conditions of rotating machinery can be identified sequentially. Practical examples of fault diagnosis for a roller bearing are shown to verify that the method is effective. PMID- 22778623 TI - A fast response highly selective probe for the detection of glutathione in human blood plasma. AB - A fluorescent probe for glutathione (GSH) detection was developed. Our study indicates a possible mechanism which couples a conjugate addition and micelle catalyzed large membered ring formation/elimination sequence. This method enables excellent selectivity towards GSH over other biological thiols such as cysteine (Cys) and homocysteine (Hcy). The proposed method is precise with a relative standard deviation (R.S.D) lower than 6% (n = 3) and has been successfully applied to determine GSH in human plasma with recoveries between 99.2% and 102.3%. PMID- 22778624 TI - Evaluation of the correlation between focal adhesion kinase phosphorylation and cell adhesion force using "DEP" technology. AB - Dielectrophoresis (DEP) is the phenomenon in which a particle, such as a living cell, is polarized and moved by electrical gravity in a non-uniform electric field. In the present study, the DEP force is utilized to act on the cells to induce spatial movement for investigating the correlation between the cell adhesion force and activation level of focal adhesion kinase (FAK). The DEP force produced by the non-uniform electric field was used to measure the cell adhesion force of ECV304 cells, on type 1 collagen (COL1)- and fibronectin (FN)-coated polydimethylsiloxane (PDMS) membranes. For COL1-coating, ECV304 cells revealed weak and variable adhesion force (0.343-0.760 nN) in the first eight hours of incubation. Interestingly, the cell adhesion force of ECV304 at two and five hours of cultivation was significantly high and matched their FAK activation level. In comparison, ECV304 on FN-coated membrane had higher and more stable cell adhesion force (0.577-2.053 nN). FN coating intensified the cell adhesion force of ECV304 with culture time and similar outcome was present on the activation level of FAK. Therefore, this study demonstrated a relationship between cell adhesion force and FAK activation level that was dependent on the choice of the extracellular matrix (ECM) component. Subsequently, two tyrosine kinase inhibitors (AG18 and genistein) and one PI3K inhibitor (LY294002) were applied to study the influence of protein phosphorylation on the cell adhesion force. FAK plays an important role on cell attachment and DEP force measurement is a useful technique for studying cell adhesion. PMID- 22778625 TI - Fusion-triggered switching of enzymatic activity on an artificial cell membrane. AB - A nanosensory membrane device was constructed for detecting liposome fusion through changes in an enzymatic activity. Inspired by a biological signal transduction system, the device design involved functionalized liposomal membranes prepared by self-assembly of the following molecular components: a synthetic peptide lipid and a phospholipid as matrix membrane components, a Schiff's base of pyridoxal 5'-phosphate with phosphatidylethanolamine as a thermo responsive artificial receptor, NADH-dependent L-lactate dehydrogenase as a signal amplifier, and Cu(2+) ion as a signal mediator between the receptor and enzyme. The enzymatic activity of the membrane device was adjustable by changing the matrix lipid composition, reflecting the thermotropic phase transition behavior of the lipid membranes, which in turn controlled receptor binding affinity toward the enzyme-inhibiting mediator species. When an effective fusogen anionic polymer was added to these cationic liposomes, membrane fusion occurred, and the functionalized liposomal membranes responded with changes in enzymatic activity, thus serving as an effective nanosensory device for liposome fusion detection. PMID- 22778626 TI - TNF as biomarker for rapid quantification of active Staphylococcus enterotoxin A in food. AB - Staphylococcus aureus is a major bacterial pathogen which causes clinical infections and food poisoning. This bacterium produces a group of twenty-one enterotoxins (SEs). These enterotoxins have two separate but related biological activities. They cause gastroenteritis and function as superantigens that activate large numbers of T cells. The current method for detection of enterotoxins activity is an in vivo monkey or kitten bioassay; however, this method is not practical to test on a large number of samples. Several immunological assays have been developed however, but these assays cannot distinguish between active toxin which causes food poisoning and inactive toxin, which can bind antibody, but shows no toxicity. The current study demonstrates that short term ex vivo exposure of primary naive CD4(+) T-cells or splenocytes to SEA induces differential expression and secretion of tumor necrosis factor (TNF) protein. We used immunomagnetic beads coated with anti-SEA antibody to specifically isolate SEA from food. After the eluted toxin was added to the cells SEA biological activity was measured by quantifying TNF protein expression or secretion. PMID- 22778627 TI - Eag1 channels as potential cancer biomarkers. AB - Cancer is a leading cause of death worldwide. New early tumor markers are needed to treat the disease at curable stages. In addition, new therapeutic targets are required to treat patients not responding to available treatments. Ion channels play major roles in health and disease, including cancer. Actually, several ion channels have been suggested as potential tumor markers and therapeutic targets for different types of malignancies. One of most studied ion channels in cancer is the voltage-gated potassium channel Eag1 (ether a go-go 1), which has a high potential to be used as a cancer biomarker. Eag1 is expressed in most human tumors, in contrast to its restricted distribution in healthy tissues. Several findings suggest Eag1 as a potential early marker for cervical, colon, and breast cancer. In addition, because Eag1 amplification/expression is associated with poor survival in leukemia, colon and ovarian cancer patients, it has also been proposed as a prognosis marker. Moreover, inhibition of either expression or activity of Eag1 leads to reduced proliferation of cancer cells, making Eag1 a potential anticancer target. Using Eag1 in cancer detection programs could help to reduce mortality from this disease. PMID- 22778629 TI - Improved maturity and ripeness classifications of Magnifera Indica cv. Harumanis mangoes through sensor fusion of an electronic nose and acoustic sensor. AB - In recent years, there have been a number of reported studies on the use of non destructive techniques to evaluate and determine mango maturity and ripeness levels. However, most of these reported works were conducted using single modality sensing systems, either using an electronic nose, acoustics or other non destructive measurements. This paper presents the work on the classification of mangoes (Magnifera Indica cv. Harumanis) maturity and ripeness levels using fusion of the data of an electronic nose and an acoustic sensor. Three groups of samples each from two different harvesting times (week 7 and week 8) were evaluated by the e-nose and then followed by the acoustic sensor. Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were able to discriminate the mango harvested at week 7 and week 8 based solely on the aroma and volatile gases released from the mangoes. However, when six different groups of different maturity and ripeness levels were combined in one classification analysis, both PCA and LDA were unable to discriminate the age difference of the Harumanis mangoes. Instead of six different groups, only four were observed using the LDA, while PCA showed only two distinct groups. By applying a low level data fusion technique on the e-nose and acoustic data, the classification for maturity and ripeness levels using LDA was improved. However, no significant improvement was observed using PCA with data fusion technique. Further work using a hybrid LDA-Competitive Learning Neural Network was performed to validate the fusion technique and classify the samples. It was found that the LDA-CLNN was also improved significantly when data fusion was applied. PMID- 22778628 TI - A critical review of glucose biosensors based on carbon nanomaterials: carbon nanotubes and graphene. AB - There has been an explosion of research into the physical and chemical properties of carbon-based nanomaterials, since the discovery of carbon nanotubes (CNTs) by Iijima in 1991. Carbon nanomaterials offer unique advantages in several areas, like high surface-volume ratio, high electrical conductivity, chemical stability and strong mechanical strength, and are thus frequently being incorporated into sensing elements. Carbon nanomaterial-based sensors generally have higher sensitivities and a lower detection limit than conventional ones. In this review, a brief history of glucose biosensors is firstly presented. The carbon nanotube and grapheme-based biosensors, are introduced in Sections 3 and 4, respectively, which cover synthesis methods, up-to-date sensing approaches and nonenzymatic hybrid sensors. Finally, we briefly outline the current status and future direction for carbon nanomaterials to be used in the sensing area. PMID- 22778630 TI - Sensing with superconducting point contacts. AB - Superconducting point contacts have been used for measuring magnetic polarizations, identifying magnetic impurities, electronic structures, and even the vibrational modes of small molecules. Due to intrinsically small energy scale in the subgap structures of the supercurrent determined by the size of the superconducting energy gap, superconductors provide ultrahigh sensitivities for high resolution spectroscopies. The so-called Andreev reflection process between normal metal and superconductor carries complex and rich information which can be utilized as powerful sensor when fully exploited. In this review, we would discuss recent experimental and theoretical developments in the supercurrent transport through superconducting point contacts and their relevance to sensing applications, and we would highlight their current issues and potentials. A true utilization of the method based on Andreev reflection analysis opens up possibilities for a new class of ultrasensitive sensors. PMID- 22778631 TI - A stress sensor based on Galvanic Skin Response (GSR) controlled by ZigBee. AB - Sometimes, one needs to control different emotional situations which can lead the person suffering them to dangerous situations, in both the medium and short term. There are studies which indicate that stress increases the risk of cardiac problems. In this study we have designed and built a stress sensor based on Galvanic Skin Response (GSR), and controlled by ZigBee. In order to check the device's performance, we have used 16 adults (eight women and eight men) who completed different tests requiring a certain degree of effort, such as mathematical operations or breathing deeply. On completion, we appreciated that GSR is able to detect the different states of each user with a success rate of 76.56%. In the future, we plan to create an algorithm which is able to differentiate between each state. PMID- 22778632 TI - Inertial sensor-based methods in walking speed estimation: a systematic review. AB - Self-selected walking speed is an important measure of ambulation ability used in various clinical gait experiments. Inertial sensors, i.e., accelerometers and gyroscopes, have been gradually introduced to estimate walking speed. This research area has attracted a lot of attention for the past two decades, and the trend is continuing due to the improvement of performance and decrease in cost of the miniature inertial sensors. With the intention of understanding the state of the art of current development in this area, a systematic review on the exiting methods was done in the following electronic engines/databases: PubMed, ISI Web of Knowledge, SportDiscus and IEEE Xplore. Sixteen journal articles and papers in proceedings focusing on inertial sensor based walking speed estimation were fully reviewed. The existing methods were categorized by sensor specification, sensor attachment location, experimental design, and walking speed estimation algorithm. PMID- 22778633 TI - Self-learning variable structure control for a class of sensor-actuator systems. AB - Variable structure strategy is widely used for the control of sensor-actuator systems modeled by Euler-Lagrange equations. However, accurate knowledge on the model structure and model parameters are often required for the control design. In this paper, we consider model-free variable structure control of a class of sensor-actuator systems, where only the online input and output of the system are available while the mathematic model of the system is unknown. The problem is formulated from an optimal control perspective and the implicit form of the control law are analytically obtained by using the principle of optimality. The control law and the optimal cost function are explicitly solved iteratively. Simulations demonstrate the effectiveness and the efficiency of the proposed method. PMID- 22778638 TI - On cup anemometer rotor aerodynamics. AB - The influence of anemometer rotor shape parameters, such as the cups' front area or their center rotation radius on the anemometer's performance was analyzed. This analysis was based on calibrations performed on two different anemometers (one based on magnet system output signal, and the other one based on an opto electronic system output signal), tested with 21 different rotors. The results were compared to the ones resulting from classical analytical models. The results clearly showed a linear dependency of both calibration constants, the slope and the offset, on the cups' center rotation radius, the influence of the front area of the cups also being observed. The analytical model of Kondo et al. was proved to be accurate if it is based on precise data related to the aerodynamic behavior of a rotor's cup. PMID- 22778634 TI - An event driven hybrid identity management approach to privacy enhanced e-health. AB - Credential-based authorization offers interesting advantages for ubiquitous scenarios involving limited devices such as sensors and personal mobile equipment: the verification can be done locally; it offers a more reduced computational cost than its competitors for issuing, storing, and verification; and it naturally supports rights delegation. The main drawback is the revocation of rights. Revocation requires handling potentially large revocation lists, or using protocols to check the revocation status, bringing extra communication costs not acceptable for sensors and other limited devices. Moreover, the effective revocation consent--considered as a privacy rule in sensitive scenarios -has not been fully addressed. This paper proposes an event-based mechanism empowering a new concept, the sleepyhead credentials, which allows to substitute time constraints and explicit revocation by activating and deactivating authorization rights according to events. Our approach is to integrate this concept in IdM systems in a hybrid model supporting delegation, which can be an interesting alternative for scenarios where revocation of consent and user privacy are critical. The delegation includes a SAML compliant protocol, which we have validated through a proof-of-concept implementation. This article also explains the mathematical model describing the event-based model and offers estimations of the overhead introduced by the system. The paper focus on health care scenarios, where we show the flexibility of the proposed event-based user consent revocation mechanism. PMID- 22778637 TI - A polymer optical fiber fuel level sensor: application to paramotoring and powered paragliding. AB - A low-cost intensity-based polymer optical fiber (POF) sensor for fuel level measurements in paramotoring and powered paragliding is presented, exploiting the advantages of the optical fiber sensing technology. Experimental results demonstrate that the best option can be performed by stripping the fiber at the desired discrete points to measure the fuel level as well as with a gauge-shape fiber bending. The prototype has a good linearity, better than 4% full scale (F.S.), and sensitivity around 0.5 V per bend are obtained. Hysteresis due to residual fluid at the sensing points is found to be less than 9% F.S. PMID- 22778635 TI - Using LS-SVM based motion recognition for smartphone indoor wireless positioning. AB - The paper presents an indoor navigation solution by combining physical motion recognition with wireless positioning. Twenty-seven simple features are extracted from the built-in accelerometers and magnetometers in a smartphone. Eight common motion states used during indoor navigation are detected by a Least Square Support Vector Machines (LS-SVM) classification algorithm, e.g., static, standing with hand swinging, normal walking while holding the phone in hand, normal walking with hand swinging, fast walking, U-turning, going up stairs, and going down stairs. The results indicate that the motion states are recognized with an accuracy of up to 95.53% for the test cases employed in this study. A motion recognition assisted wireless positioning approach is applied to determine the position of a mobile user. Field tests show a 1.22 m mean error in "Static Tests" and a 3.53 m in "Stop-Go Tests". PMID- 22778639 TI - Mobile, collaborative situated knowledge creation for urban planning. AB - Geo-collaboration is an emerging research area in computer sciences studying the way spatial, geographically referenced information and communication technologies can support collaborative activities. Scenarios in which information associated to its physical location are of paramount importance are often referred as Situated Knowledge Creation scenarios. To date there are few computer systems supporting knowledge creation that explicitly incorporate physical context as part of the knowledge being managed in mobile face-to-face scenarios. This work presents a collaborative software application supporting visually-geo-referenced knowledge creation in mobile working scenarios while the users are interacting face-to-face. The system allows to manage data information associated to specific physical locations for knowledge creation processes in the field, such as urban planning, identifying specific physical locations, territorial management, etc.; using Tablet-PCs and GPS in order to geo-reference data and information. It presents a model for developing mobile applications supporting situated knowledge creation in the field, introducing the requirements for such an application and the functionalities it should have in order to fulfill them. The paper also presents the results of utility and usability evaluations. PMID- 22778640 TI - FPGA implementation of Generalized Hebbian Algorithm for texture classification. AB - This paper presents a novel hardware architecture for principal component analysis. The architecture is based on the Generalized Hebbian Algorithm (GHA) because of its simplicity and effectiveness. The architecture is separated into three portions: the weight vector updating unit, the principal computation unit and the memory unit. In the weight vector updating unit, the computation of different synaptic weight vectors shares the same circuit for reducing the area costs. To show the effectiveness of the circuit, a texture classification system based on the proposed architecture is physically implemented by Field Programmable Gate Array (FPGA). It is embedded in a System-On-Programmable-Chip (SOPC) platform for performance measurement. Experimental results show that the proposed architecture is an efficient design for attaining both high speed performance and low area costs. PMID- 22778636 TI - luxS mutant regulation: quorum sensing impairment or methylation disorder? AB - AI-2-mediated quorum sensing has been identified in various bacteria, including both Gram-negative and Gram-positive species, and numerous phenotypes have been reported to be regulated by this mechanism, using the luxS-mutant strain. But the AI-2 production process confused this regulatory function; some considered this regulation as the result of a metabolic change, which refers to an important metabolic cycle named activated methyl cycle (AMC), caused by luxS-mutant simultaneously with the defect of AI-2. Herein we hypothesized that the quorum sensing system--not the metabolic aspect--is responsible for such a regulatory function. In this study, we constructed plasmids infused with sahH and induced protein expression in the luxS-mutant strain to make the quorum-sensing system and metabolic system independent. The biofilm-related genes were investigated by real-time polymerase chain reaction (PCR), and the results demonstrated that the quorum-sensing completed strain restored the gene expression of the defective strain, but the metabolically completed one did not. This evidence supported our hypothesis that the autoinducer-2-mediated, quorum-sensing system, not the AMC, was responsible for luxS mutant regulation. PMID- 22778641 TI - Wireless biosensor system for real-time L-lactic acid monitoring in fish. AB - We have developed a wireless biosensor system to continuously monitor L-lactic acid concentrations in fish. The blood L-lactic acid level of fish is a barometer of stress. The biosensor comprised Pt-Ir wire (phi0.178 mm) as the working electrode and Ag/AgCl paste as the reference electrode. Lactate oxidase was immobilized on the working electrode using glutaraldehyde. The sensor calibration was linear and good correlated with L-lactic acid levels (R = 0.9959) in the range of 0.04 to 6.0 mg . dL(-1). We used the eyeball interstitial sclera fluid (EISF) as the site of sensor implantation. The blood L-lactic acid levels correlated closely with the EISF L-lactic acid levels in the range of 3 to 13 mg . dL(-1) (R = 0.8173, n = 26). Wireless monitoring of L-lactic acid was performed using the sensor system in free-swimming fish in an aquarium. The sensor response was stable for over 60 h. Thus, our biosensor provided a rapid and convenient method for real-time monitoring of L-lactic acid levels in fish. PMID- 22778642 TI - An approach for representing sensor data to validate alerts in Ambient Assisted Living. AB - The mainstream of research in Ambient Assisted Living (AAL) is devoted to developing intelligent systems for processing the data collected through artificial sensing. Besides, there are other elements that must be considered to foster the adoption of AAL solutions in real environments. In this paper we focus on the problem of designing interfaces among caregivers and AAL systems. We present an alert management tool that supports carers in their task of validating alarms raised by the system. It generates text-based explanations--obtained through an argumentation process--of the causes leading to alarm activation along with graphical sensor information and 3D models, thus offering complementary types of information. Moreover, a guideline to use the tool when validating alerts is also provided. Finally, the functionality of the proposed tool is demonstrated through two real cases of alert. PMID- 22778643 TI - Sharing human-generated observations by integrating HMI and the Semantic Sensor Web. AB - Current "Internet of Things" concepts point to a future where connected objects gather meaningful information about their environment and share it with other objects and people. In particular, objects embedding Human Machine Interaction (HMI), such as mobile devices and, increasingly, connected vehicles, home appliances, urban interactive infrastructures, etc., may not only be conceived as sources of sensor information, but, through interaction with their users, they can also produce highly valuable context-aware human-generated observations. We believe that the great promise offered by combining and sharing all of the different sources of information available can be realized through the integration of HMI and Semantic Sensor Web technologies. This paper presents a technological framework that harmonizes two of the most influential HMI and Sensor Web initiatives: the W3C's Multimodal Architecture and Interfaces (MMI) and the Open Geospatial Consortium (OGC) Sensor Web Enablement (SWE) with its semantic extension, respectively. Although the proposed framework is general enough to be applied in a variety of connected objects integrating HMI, a particular development is presented for a connected car scenario where drivers' observations about the traffic or their environment are shared across the Semantic Sensor Web. For implementation and evaluation purposes an on-board OSGi (Open Services Gateway Initiative) architecture was built, integrating several available HMI, Sensor Web and Semantic Web technologies. A technical performance test and a conceptual validation of the scenario with potential users are reported, with results suggesting the approach is sound. PMID- 22778644 TI - Advances in atomic gyroscopes: a view from inertial navigation applications. AB - With the rapid development of modern physics, atomic gyroscopes have been demonstrated in recent years. There are two types of atomic gyroscope. The Atomic Interferometer Gyroscope (AIG), which utilizes the atomic interferometer to sense rotation, is an ultra-high precision gyroscope; and the Atomic Spin Gyroscope (ASG), which utilizes atomic spin to sense rotation, features high precision, compact size and the possibility to make a chip-scale one. Recent developments in the atomic gyroscope field have created new ways to obtain high precision gyroscopes which were previously unavailable with mechanical or optical gyroscopes, but there are still lots of problems that need to be overcome to meet the requirements of inertial navigation systems. This paper reviews the basic principles of AIG and ASG, introduces the recent progress in this area, focusing on discussing their technical difficulties for inertial navigation applications, and suggests methods for developing high performance atomic gyroscopes in the near future. PMID- 22778645 TI - Accuracy assessment of digital surface models based on WorldView-2 and ADS80 stereo remote sensing data. AB - Digital surface models (DSMs) are widely used in forest science to model the forest canopy. Stereo pairs of very high resolution satellite and digital aerial images are relatively new and their absolute accuracy for DSM generation is largely unknown. For an assessment of these input data two DSMs based on a WorldView-2 stereo pair and a ADS80 DSM were generated with photogrammetric instruments. Rational polynomial coefficients (RPCs) are defining the orientation of the WorldView-2 satellite images, which can be enhanced with ground control points (GCPs). Thus two WorldView-2 DSMs were distinguished: a WorldView-2 RPCs only DSM and a WorldView-2 GCP-enhanced RPCs DSM. The accuracy of the three DSMs was estimated with GPS measurements, manual stereo-measurements, and airborne laser scanning data (ALS). With GCP-enhanced RPCs the WorldView-2 image orientation could be optimised to a root mean square error (RMSE) of 0.56 m in planimetry and 0.32 m in height. This improvement in orientation allowed for a vertical median error of -0.24 m for the WorldView-2 GCP-enhanced RPCs DSM in flat terrain. Overall, the DSM based on ADS80 images showed the highest accuracy of the three models with a median error of 0.08 m over bare ground. As the accuracy of a DSM varies with land cover three classes were distinguished: herb and grass, forests, and artificial areas. The study suggested the ADS80 DSM to best model actual surface height in all three land cover classes, with median errors <1.1 m. The WorldView-2 GCP-enhanced RPCs model achieved good accuracy, too, with median errors of -0.43 m for the herb and grass vegetation and -0.26 m for artificial areas. Forested areas emerged as the most difficult land cover type for height modelling; still, with median errors of -1.85 m for the WorldView 2 GCP-enhanced RPCs model and -1.12 m for the ADS80 model, the input data sets evaluated here are quite promising for forest canopy modelling. PMID- 22778646 TI - Fabrication and characteristics of an nc-Si/c-Si heterojunction MOSFETs pressure sensor. AB - A novel nc-Si/c-Si heterojunction MOSFETs pressure sensor is proposed in this paper, with four p-MOSFETs with nc-Si/c-Si heterojunction as source and drain. The four p-MOSFETs are designed and fabricated on a square silicon membrane by CMOS process and MEMS technology where channel resistances of the four nc-Si/c-Si heterojunction MOSFETs form a Wheatstone bridge. When the additional pressure is P, the nc-Si/c-Si heterojunction MOSFETs pressure sensor can measure this additional pressure P. The experimental results show that when the supply voltage is 3 V, length-width (L:W) ratio is 2:1, and the silicon membrane thickness is 75 MUm, the full scale output voltage of the pressure sensor is 15.50 mV at room temperature, and pressure sensitivity is 0.097 mV/kPa. When the supply voltage and L:W ratio are the same as the above, and the silicon membrane thickness is 45 MUm, the full scale output voltage is 43.05 mV, and pressure sensitivity is 2.153 mV/kPa. Therefore, the sensor has higher sensitivity and good temperature characteristics compared to the traditional piezoresistive pressure sensor. PMID- 22778647 TI - Enabling communication in emergency response environments. AB - Effective communication among first responders during response to natural and human-made large-scale catastrophes has increased tremendously during the last decade. However, most efforts to achieve a higher degree of effectiveness in communication lack synergy between the environment and the technology involved to support first responders operations. This article presents a natural and intuitive interface to support Stigmergy; or communication through the environment, based on intuitively marking and retrieving information from the environment with a pointer. A prototype of the system was built and tested in the field, however the pointing activity revealed challenges regarding accuracy due to limitations of the sensors used. The results obtained from these field tests were the basis for this research effort and will have the potential to enable communication through the environment for first responders operating in highly dynamical and inhospitable disaster relief environments. PMID- 22778648 TI - Design of compensation coils for EMI suppression in magnetostrictive linear position sensors. AB - This paper presents recent development on magnetostrictive linear position sensors (MLPS). A new compensation coil structure improves the EMI suppression and accuracy considerably. Furthermore, experimental results indicate that the new structure can improve the accuracy to +/- 0.13 mm nearly double the +/- 0.2 mm obtained with traditional structures. As another design continuation after the differential waveguide structure, this new structure is a practical and reliable implementation technique for the commercialization of MLPS. PMID- 22778649 TI - Integral T-shaped phantom-dosimeter system to measure transverse and longitudinal dose distributions simultaneously for stereotactic radiosurgery dosimetry. AB - A T-shaped fiber-optic phantom-dosimeter system was developed using square scintillating optical fibers, a lens system, and a CMOS image camera. Images of scintillating light were used to simultaneously measure the transverse and longitudinal distributions of absorbed dose of a 6 MV photon beam with field sizes of 1 * 1 and 3 * 3 cm(2). Each optical fiber has a very small sensitive volume and the sensitive material is water equivalent. This allows the measurements of cross-beam profile as well as the percentage depth dose of small field sizes. In the case of transverse dose distribution, the measured beam profiles were gradually become uneven and the beam edge had a gentle slope with increasing depth of the PMMA phantom. In addition, the maximum dose values of longitudinal dose distribution for 6 MV photon beam with field sizes of 1 * 1 and 3 * 3 cm(2) were found to be at a depth of approximately 15 mm and the percentage depth dose of both field sizes were nearly in agreement at the skin dose level. Based on the results of this study, it is anticipated that an all-in-one phantom dosimeter can be developed to accurately measure beam profiles and dose distribution in a small irradiation fields prior to carrying out stereotactic radiosurgery. PMID- 22778650 TI - Road sign recognition with fuzzy adaptive pre-processing models. AB - A road sign recognition system based on adaptive image pre-processing models using two fuzzy inference schemes has been proposed. The first fuzzy inference scheme is to check the changes of the light illumination and rich red color of a frame image by the checking areas. The other is to check the variance of vehicle's speed and angle of steering wheel to select an adaptive size and position of the detection area. The Adaboost classifier was employed to detect the road sign candidates from an image and the support vector machine technique was employed to recognize the content of the road sign candidates. The prohibitory and warning road traffic signs are the processing targets in this research. The detection rate in the detection phase is 97.42%. In the recognition phase, the recognition rate is 93.04%. The total accuracy rate of the system is 92.47%. For video sequences, the best accuracy rate is 90.54%, and the average accuracy rate is 80.17%. The average computing time is 51.86 milliseconds per frame. The proposed system can not only overcome low illumination and rich red color around the road sign problems but also offer high detection rates and high computing performance. PMID- 22778651 TI - Temperature drift compensation for Hemispherical Resonator Gyro based on natural frequency. AB - Temperature changes have a strong effect on Hemispherical Resonator Gyro (HRG) output; therefore, it is of vital importance to observe their influence and then make necessary compensations. In this paper, a temperature compensation model for HRG based on the natural frequency of the resonator is established and then temperature drift compensations are accomplished. To begin with, a math model of the relationship between the temperature and the natural frequency of HRG is set up. Then, the math model is written into a Taylor expansion expression and the expansion coefficients are calibrated through temperature experiments. The experimental results show that the frequency changes correspond to temperature changes and each temperature only corresponds to one natural frequency, so the output of HRG can be compensated through the natural frequency of the resonator instead of the temperature itself. As a result, compensations are made for the output drift of HRG based on natural frequency through a stepwise linear regression method. The compensation results show that temperature-frequency method is valid and suitable for the gyroscope drift compensation, which would ensure HRG's application in a larger temperature range in the future. PMID- 22778652 TI - Electromagnetic field analysis and modeling of a relative position detection sensor for high speed maglev trains. AB - The long stator track for high speed maglev trains has a tooth-slot structure. The sensor obtains precise relative position information for the traction system by detecting the long stator tooth-slot structure based on nondestructive detection technology. The magnetic field modeling of the sensor is a typical three-dimensional (3-D) electromagnetic problem with complex boundary conditions, and is studied semi-analytically in this paper. A second-order vector potential (SOVP) is introduced to simplify the vector field problem to a scalar field one, the solution of which can be expressed in terms of series expansions according to Multipole Theory (MT) and the New Equivalent Source (NES) method. The coefficients of the expansions are determined by the least squares method based on the boundary conditions. Then, the solution is compared to the simulation result through Finite Element Analysis (FEA). The comparison results show that the semi-analytical solution agrees approximately with the numerical solution. Finally, based on electromagnetic modeling, a difference coil structure is designed to improve the sensitivity and accuracy of the sensor. PMID- 22778653 TI - Evaluation of the impact of furniture on communications performance for ubiquitous deployment of Wireless Sensor Networks in smart homes. AB - The extensions of the environment with the integration of sensing systems in any space, in conjunction with ubiquitous computing are enabling the so-called Smart Space Sensor Networks. This new generation of networks are offering full connectivity with any object, through the Internet of Things (IoT) and/or the Web, i.e., the Web of Things. These connectivity capabilities are making it feasible to sense the behaviours of people at home and act accordingly. These sensing systems must be integrated within typical elements found at home such as furniture. For that reason, this work considers furniture as an interesting element for the transparent location of sensors. Furniture is a ubiquitous object, i.e., it can be found everywhere at home or the office, and it can integrate and hide the sensors of a network. This work addresses the lack of an exhaustive study of the effect of furniture on signal losses. In addition an easy to-use tool for estimating the robustness of the communication channel among the sensor nodes and gateways is proposed. Specifically, the losses in a sensor network signal due to the materials found within the communication link are evaluated. Then, this work proposes a software tool that gathers the obtained results and is capable of evaluating the impact of a given set of materials on the communications. This tool also provides a mechanism to optimize the sensor network deployments during the definition of smart spaces. Specifically, it provides information such as: maximum distances between sensor nodes, most suitable type of furniture to integrate sensors, or battery life of sensor nodes. This tool has been validated empirically in the lab, and it is currently being used by several enterprise partners of the Technological Centre of Furniture and Wood in the southeast of Spain. PMID- 22778654 TI - Using micromechanical resonators to measure rheological properties and alcohol content of model solutions and commercial beverages. AB - Micromechanic resonators provide a small-volume and potentially high-throughput method to determine rheological properties of fluids. Here we explore the accuracy in measuring mass density and viscosity of ethanol-water and glycerol water model solutions, using a simple and easily implemented model to deduce the hydrodynamic effects on resonating cantilevers of various length-to-width aspect ratios. We next show that these measurements can be extended to determine the alcohol percentage of both model solutions and commercial beverages such as beer, wine and liquor. This demonstrates how micromechanical resonators can be used for quality control of every-day drinks. PMID- 22778655 TI - Structure and process of infrared hot electron transistor arrays. AB - An infrared hot-electron transistor (IHET) 5 * 8 array with a common base configuration that allows two-terminal readout integration was investigated and fabricated for the first time. The IHET structure provides a maximum factor of six in improvement in the photocurrent to dark current ratio compared to the basic quantum well infrared photodetector (QWIP), and hence it improved the array S/N ratio by the same factor. The study also showed for the first time that there is no electrical cross-talk among individual detectors, even though they share the same emitter and base contacts. Thus, the IHET structure is compatible with existing electronic readout circuits for photoconductors in producing sensitive focal plane arrays. PMID- 22778657 TI - Architecture for improving terrestrial logistics based on the Web of Things. AB - Technological advances for improving supply chain efficiency present three key challenges for managing goods: tracking, tracing and monitoring (TTM), in order to satisfy the requirements for products such as perishable goods where the European Legislations requires them to ship within a prescribed temperature range to ensure freshness and suitability for consumption. The proposed system integrates RFID for tracking and tracing through a distributed architecture developed for heavy goods vehicles, and the sensors embedded in the SunSPOT platform for monitoring the goods transported based on the concept of the Internet of Things. This paper presents how the Internet of Things is integrated for improving terrestrial logistics offering a comprehensive and flexible architecture, with high scalability, according to the specific needs for reaching an item-level continuous monitoring solution. The major contribution from this work is the optimization of the Embedded Web Services based on RESTful (Web of Things) for the access to TTM services at any time during the transportation of goods. Specifically, it has been extended the monitoring patterns such as observe and blockwise transfer for the requirements from the continuous conditional monitoring, and for the transfer of full inventories and partial ones based on conditional queries. In definitive, this work presents an evolution of the previous TTM solutions, which were limited to trailer identification and environment monitoring, to a solution which is able to provide an exhaustive item level monitoring, required for several use cases. This exhaustive monitoring has required new communication capabilities through the Web of Things, which has been optimized with the use and improvement of a set of communications patterns. PMID- 22778656 TI - Electrochemical detection of anti-breast-cancer agents in human serum by cytochrome P450-coated carbon nanotubes. AB - We report on the electrochemical detection of anti-cancer drugs in human serum with sensitivity values in the range of 8-925 nA/MUM. Multi-walled carbon nanotubes were functionalized with three different cytochrome P450 isoforms (CYP1A2, CYP2B6, and CYP3A4). A model used to effectively describe the cytochrome P450 deposition onto carbon nanotubes was confirmed by Monte Carlo simulations. Voltammetric measurements were performed in phosphate buffer saline (PBS) as well as in human serum, giving well-defined current responses upon addition of increasing concentrations of anti-cancer drugs. The results assert the capability to measure concentration of drugs in the pharmacological ranges in human serum. Another important result is the possibility to detect pairs of drugs present in the same sample, which is highly required in case of therapies with high side effects risk and in anti-cancer pharmacological treatments based on mixtures of different drugs. Our technology holds potentials for inexpensive multi-panel drug monitoring in personalized therapy. PMID- 22778658 TI - A critical review of published data on the gas temperature and the electron density in the electrolyte cathode atmospheric glow discharges. AB - Electrolyte Cathode Discharge (ELCAD) spectrometry, a novel sensitive multielement direct analytical method for metal traces in aqueous solutions, was introduced in 1993 as a new sensing principle. Since then several works have tried to develop an operational mechanism for this exotic atmospheric glow plasma technique, however these attempts cannot be combined into a valid model description. In this review we summarize the conceptual and technical problems we found in this upcoming research field of direct sensors. The T(G) gas temperature and the n(e) electron density values published up to now for ELCAD are very confusing. These data were evaluated by three conditions. The first is the gas composition of the ELCAD plasma, since T(G) was determined from the emitted intensity of the N(2) and OH bands. Secondly, since the ELCAD is an atmospheric glow discharge, thus, the obtained T(G) has to be close to the T(e) electron temperature. This can be used for the mutual validation of the received temperature data. Thirdly, as a consequence of the second condition, the values of T(G) and n(e) have to agree with the Engel-Brown approximation of the Saha equation related to weakly ionized glow discharge plasmas. Application of non adequate experimental methods and theoretical treatment leads to unreliable descriptions which cannot be used to optimize the detector performance. PMID- 22778659 TI - IVAN: intelligent van for the distribution of pharmaceutical drugs. AB - This paper describes a telematic system based on an intelligent van which is capable of tracing pharmaceutical drugs over delivery routes from a warehouse to pharmacies, without altering carriers' daily conventional tasks. The intelligent van understands its environment, taking into account its location, the assets and the predefined delivery route; with the capability of reporting incidences to carriers in case of failure according to the established distribution plan. It is a non-intrusive solution which represents a successful experience of using smart environments and an optimized Radio Frequency Identification (RFID) embedded system in a viable way to resolve a real industrial need in the pharmaceutical industry. The combination of deterministic modeling of the indoor vehicle, the implementation of an ad-hoc radiating element and an agile software platform within an overall system architecture leads to a competitive, flexible and scalable solution. PMID- 22778660 TI - Energy performance assessment of virtualization technologies using small environmental monitoring sensors. AB - The increasing trends of electrical consumption within data centres are a growing concern for business owners as they are quickly becoming a large fraction of the total cost of ownership. Ultra small sensors could be deployed within a data centre to monitor environmental factors to lower the electrical costs and improve the energy efficiency. Since servers and air conditioners represent the top users of electrical power in the data centre, this research sets out to explore methods from each subsystem of the data centre as part of an overall energy efficient solution. In this paper, we investigate the current trends of Green IT awareness and how the deployment of small environmental sensors and Site Infrastructure equipment optimization techniques which can offer a solution to a global issue by reducing carbon emissions. PMID- 22778661 TI - Dynamic Structural Health Monitoring of slender structures using optical sensors. AB - In this paper we summarize the research activities at the Instituto de Telecomunicacoes--Polo de Aveiro and University of Aveiro, in the field of fiber Bragg grating based sensors and their applications in dynamic measurements for Structural Health Monitoring of slender structures such as towers. In this work we describe the implementation of an optical biaxial accelerometer based on fiber Bragg gratings inscribed on optical fibers. The proof-of-concept was done with the dynamic monitoring of a reinforced concrete structure and a slender metallic telecommunication tower. Those structures were found to be suitable to demonstrate the feasibility of FBG accelerometers to obtain the structures' natural frequencies, which are the key parameters in Structural Health Monitoring and in the calibration of numerical models used to simulate the structure behavior. PMID- 22778663 TI - Tip-jump response of an amplitude-modulated Atomic Force Microscope. AB - The dynamic behaviors of an Atomic Force Microscope are of interest, and variously unpredictable phenomena are experimentally measured. In practical measurements, researchers have proposed many methods for avoiding these uncertainties. However, causes of these phenomena are still hard to demonstrate in simulation. To demonstrate these phenomena, this paper claims the tip-jump motion is a predictable process, and the jumping kinetic energy results in different nonlinear phenomena. It emphasizes the variation in the eigenvalues of an AFM with tip-sample distance. This requirement ensures the phase transformations from one associated with the oscillation mode to one associated with the tip-jump/sample-contact mode. Also, multi-modal analysis was utilized to ensure the modal transformation in varying tip-sample distances. In the presented model, oscillations with various tip-sample distances and with various excitation frequencies and amplitudes were compared. The results reveal that the tip-jump motion separates the oscillation orbit into two regions, and the jumping kinetic energy, comparing with the superficial potential energy, leads the oscillation to be bistable or intermittent. The sample-contact condition associates to bifurcation and chaos. Additionally, the jumping is a strong motion that occurs before the tip-sample contacts, and this motion signal can replace the sample contact-signal to avoid destroying the sample. PMID- 22778664 TI - Flexible graphite-on-paper piezoresistive sensors. AB - We demonstrate novel graphite-on-paper piezoresistive devices. The graphite was used as sensing component. The fabrication process can be finished in a short time with simple tools (e.g., a scissor and a pencil). A small array of six paper based piezoresistive devices is made. The whole device is flexible. The test results showed that the change of resistance was proportional to the applied force. A paper-based weighing balance was also made as an example of applications. This novel array of paper-based piezoresistive devices will open wide applications in force and acceleration sensing areas. PMID- 22778662 TI - Detection of AI-2 receptors in genomes of Enterobacteriaceae suggests a role of type-2 quorum sensing in closed ecosystems. AB - The LuxS enzyme, an S-ribosyl-homocysteine lyase, catalyzes the production of the signal precursor for autoinducer-2 mediated quorum sensing (QS-2) in Vibrio. Its widespread occurrence among bacteria is often considered the evidence for a universal language for interspecies communication. Presence of the luxS gene and production of the autoinducer-2 (AI-2) signal have repeatedly been the only evidences presented to assign a functional QS-2 to the most diverse species. In fact, LuxS has a primary metabolic role as part of the activated methyl cycle. In this review we have analyzed the distribution of QS-2 related genes in Enterobacteriaceae by moving the focus of the investigation from AI-2 production to the detection of potential AI-2 receptors. The latter are common in pathogens or endosymbionts of animals, but were also found in a limited number of Enterobacteriaceae of the genera Enterobacter, Klebsiella, and Pantoea that live in close association with plants or fungi. Although a precise function of QS-2 in these species has not been identified, they all show an endophytic or endosymbiontic lifestyle that suggests a role of type-2 quorum sensing in the adaptation to closed ecosystems. PMID- 22778665 TI - Categorization of indoor places using the Kinect sensor. AB - The categorization of places in indoor environments is an important capability for service robots working and interacting with humans. In this paper we present a method to categorize different areas in indoor environments using a mobile robot equipped with a Kinect camera. Our approach transforms depth and grey scale images taken at each place into histograms of local binary patterns (LBPs) whose dimensionality is further reduced following a uniform criterion. The histograms are then combined into a single feature vector which is categorized using a supervised method. In this work we compare the performance of support vector machines and random forests as supervised classifiers. Finally, we apply our technique to distinguish five different place categories: corridors, laboratories, offices, kitchens, and study rooms. Experimental results show that we can categorize these places with high accuracy using our approach. PMID- 22778666 TI - Blurred star image processing for star sensors under dynamic conditions. AB - The precision of star point location is significant to identify the star map and to acquire the aircraft attitude for star sensors. Under dynamic conditions, star images are not only corrupted by various noises, but also blurred due to the angular rate of the star sensor. According to different angular rates under dynamic conditions, a novel method is proposed in this article, which includes a denoising method based on adaptive wavelet threshold and a restoration method based on the large angular rate. The adaptive threshold is adopted for denoising the star image when the angular rate is in the dynamic range. Then, the mathematical model of motion blur is deduced so as to restore the blurred star map due to large angular rate. Simulation results validate the effectiveness of the proposed method, which is suitable for blurred star image processing and practical for attitude determination of satellites under dynamic conditions. PMID- 22778667 TI - Development of a voice activity controlled noise canceller. AB - In this paper, a variable threshold voice activity detector (VAD) is developed to control the operation of a two-sensor adaptive noise canceller (ANC). The VAD prohibits the reference input of the ANC from containing some strength of actual speech signal during adaptation periods. The novelty of this approach resides in using the residual output from the noise canceller to control the decisions made by the VAD. Thresholds of full-band energy and zero-crossing features are adjusted according to the residual output of the adaptive filter. Performance evaluation of the proposed approach is quoted in terms of signal to noise ratio improvements as well mean square error (MSE) convergence of the ANC. The new approach showed an improved noise cancellation performance when tested under several types of environmental noise. Furthermore, the computational power of the adaptive process is reduced since the output of the adaptive filter is efficiently calculated only during non-speech periods. PMID- 22778668 TI - A compact optical instrument with artificial neural network for pH determination. AB - The aim of this work was the determination of pH with a sensor array-based optical portable instrument. This sensor array consists of eleven membranes with selective colour changes at different pH intervals. The method for the pH calculation is based on the implementation of artificial neural networks that use the responses of the membranes to generate a final pH value. A multi-objective algorithm was used to select the minimum number of sensing elements required to achieve an accurate pH determination from the neural network, and also to minimise the network size. This helps to minimise instrument and array development costs and save on microprocessor energy consumption. A set of artificial neural networks that fulfils these requirements is proposed using different combinations of the membranes in the sensor array, and is evaluated in terms of accuracy and reliability. In the end, the network including the response of the eleven membranes in the sensor was selected for validation in the instrument prototype because of its high accuracy. The performance of the instrument was evaluated by measuring the pH of a large set of real samples, showing that high precision can be obtained in the full range. PMID- 22778669 TI - Transtheoretical Model Constructs for Physical Activity Behavior are Invariant across Time among Ethnically Diverse Adults in Hawaii. AB - OBJECTIVES: Physical activity (PA) research applying the Transtheoretical Model (TTM) to examine group differences and/or change over time requires preliminary evidence of factorial validity and invariance. The current study examined the factorial validity and longitudinal invariance of TTM constructs recently revised for PA. METHOD: Participants from an ethnically diverse sample in Hawaii (N=700) completed questionnaires capturing each TTM construct. RESULTS: Factorial validity was confirmed for each construct using confirmatory factor analysis with full-information maximum likelihood. Longitudinal invariance was evidenced across a shorter (3-month) and longer (6-month) time period via nested model comparisons. CONCLUSIONS: The questionnaires for each validated TTM construct are provided, and can now be generalized across similar subgroups and time points. Further validation of the provided measures is suggested in additional populations and across extended time points. PMID- 22778671 TI - From the Editor's Desk. PMID- 22778670 TI - Effect of growth medium pH of Aeropyrum pernix on structural properties and fluidity of archaeosomes. AB - The influence of pH (6.0; 7.0; 8.0) of the growth medium of Aeropyrum pernix K1 on the structural organization and fluidity of archaeosomes prepared from a polar lipid methanol fraction (PLMF) was investigated using fluorescence anisotropy and electron paramagnetic resonance (EPR) spectroscopy. Fluorescence anisotropy of the lipophilic fluorofore 1,6-diphenyl-1,3,5-hexatriene and empirical correlation time of the spin probe methylester of 5-doxylpalmitate revealed gradual changes with increasing temperature for the pH. A similar effect has been observed by using the trimethylammonium-6-diphenyl-1,3,5-hexatriene, although the temperature changes were much smaller. As the fluorescence steady-state anisotropy and the empirical correlation time obtained directly from the EPR spectra alone did not provide detailed structural information, the EPR spectra were analysed by computer simulation. This analysis showed that the archaeosome membranes are heterogeneous and composed of several regions with different modes of spin-probe motion at temperatures below 70 degrees C. At higher temperatures, these membranes become more homogeneous and can be described by only one spectral component. Both methods indicate that the pH of the growth medium of A. pernix does not significantly influence its average membrane fluidity. These results are in accordance with TLC analysis of isolated lipids, which show no significant differences between PLMF isolated from A. pernix grown in medium with different pH. PMID- 22778672 TI - Bioethics in practice: a quarterly column about medical ethics - assessment of patients' capacity to make medical decisions. PMID- 22778673 TI - Specialized ambulatory anesthesia teams contribute to decreased ambulatory surgery recovery room length of stay. AB - BACKGROUND: Many institutions have organized specialized groups of ambulatory surgery anesthesiologists with the aim of improving ambulatory surgery patient care and efficiency. We hypothesized that specialized ambulatory anesthesia teams produce better patient outcomes such as lower postoperative nausea and vomiting (PONV) rates, lower postoperative pain scores, and shorter postanesthesia care unit (PACU) lengths of stay (LOS). METHODS: In this prospective observational study, we collected outcomes data on 1,299 patients including incidence of PONV, PACU LOS, maximum and average pain scores, amount of postoperative opioid use, and rescue antiemetic use. RESULTS: Ambulatory anesthesiologists had statistically shorter phase 2 PACU LOS times (P < .05) and overall recovery times (P < .01). The PONV incidence odds ratio for ambulatory versus nonambulatory anesthesiologists was 1.31 (95% CI 1.01-1.72). We found no significant difference in the amount of postoperative opioid use, maximum postoperative pain scores, or PACU phase 1 LOS time. CONCLUSIONS: The decreased PACU LOS for the study group's patients occurred despite the increased incidence of PONV. Ambulatory anesthesiologists contributed to decreased PACU LOS while practicing evidence based anesthesia with regard to PONV and pain control. Ambulatory subspecialization may benefit institutions as a way to increase perioperative efficiency and improve surgeon and patient satisfaction. PMID- 22778674 TI - Medical management in the acute hip fracture patient: a comprehensive review for the internist. AB - Each year, more than 250,000 Americans will suffer a broken hip from a fall from no more than standing height. The National Osteoporosis Foundation estimates that more than 500,000 acute hip fractures will occur annually by the year 2040. The costs associated with this healthcare phenomenon are staggering and will continue to increase with an aging population.Hospitalists routinely comanage orthopedic patients as either consultants or as primary physicians in the hospital setting. A unique set of problems exists in this population. Among them are perioperative cardiac risk, perioperative anemia from acute blood loss, venous thromboembolism prophylaxis, and problems with the timing of surgery. It is imperative that hospitalists understand the orthopedic surgeon's point of view in managing these particular problems and become familiar with the evidence supporting or refuting treatment modalities related to these subject areas. In addition, an understanding of the anatomy and surgical options and complications related to each type of fracture allows the hospitalist to become familiar with postoperative rehabilitation needs. It cannot be overstated that addressing hip fracture prevention must be a part of every patient's perioperative care because the incidence of a repeat fracture is significant. Morbidity related to the fracture and comorbidities also need close examination.This article aims to provide a solid understanding of the issues associated with the acute hip fracture population to enhance practice and allow for the best outcome for patients. PMID- 22778675 TI - Perioperative management of neurofibromatosis type 1. AB - Neurofibromatosis type 1 (neurofibromatosis-1), a relatively common single-gene disorder, is caused by a mutation of the NF1 gene that results in a loss of activity or in a nonfunctional neurofibromin protein. Clinical anesthesiologists may find patients with neurofibromatosis-1 challenging because this condition may affect most organ systems and result in a wide variety of presentations and clinical implications. Current neurofibromatosis-1 research studies include genotype-phenotype correlations, investigation of the pathoetiology behind the different clinical manifestations of neurofibromatosis-1, and the search for treatment options for the different features of the disorder. Neurofibromatosis-1 associated complications of the central nervous, respiratory, cardiovascular, musculoskeletal, and gastrointestinal and genitourinary systems all present various degrees of considerations for anesthesiologists. Additionally, neurofibromatosis-1 has dramatic implications for pregnant women. PMID- 22778676 TI - Sleep physiology, abnormal States, and therapeutic interventions. AB - Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process. PMID- 22778677 TI - Dyed but not dead. AB - The use of vital blue dyes in sentinel lymph node mapping and biopsy is gaining popularity in the surgical management of cancer. However, intraoperative use of these dyes has associated risks for the patient. This case report and review of the literature present current medical knowledge about one of the vital blue dyes, isosulfan blue, and the associated clinical risks of this dye when used in the perioperative management of patients who undergo sentinel lymph node mapping and biopsy. PMID- 22778678 TI - Bilateral gluteal compartment syndrome following right total knee revision: a case report. AB - BACKGROUND: Gluteal compartment syndrome is a rare occurrence traditionally found in settings of extended immobilization. Thrombolytics and medications with myositis as a potential side effect have also been implicated in a few isolated cases of spontaneous compartment syndrome. Early signs are pain on passive stretching and pain out of proportion to physical examination findings. Failure to recognize and definitively treat compartment syndrome within the first 24 to 36 hours can lead to permanent limb loss and morbidity from a host of systemic complications such as hyperkalemia, renal failure, and sepsis. CASE REPORT: We report a case of bilateral gluteal compartment syndrome in a 52-year-old patient following a right total knee revision. On postoperative day 2, physical examination after the patient became agitated and in severe distress from bilateral buttock pain showed that the right and left gluteal regions were tense, hard, and erythematous. Creatinine phosphokinase and liver function tests were significantly elevated. Following emergency fasciotomy, physicians thoroughly reviewed the operative course, medication history, and imaging studies. We withdrew simvastatin, a medication associated with spontaneous compartment syndrome, from our patient's daily medications. By day of discharge, both creatinine phosphokinase and liver function problems were decreasing, and the gluteal pain had significantly resolved. The etiology of bilateral gluteal compartment syndrome in our patient could have been a combination of intraoperative length and positioning with simvastatin-induced myositis. Obesity presented an additional risk factor. CONCLUSION: This case highlights the importance of identifying patients at increased risk of compartment syndrome in the preoperative assessment and following them with more intensive intraoperative and postoperative monitoring. PMID- 22778679 TI - Epidural anesthesia for cesarean delivery in a morbidly obese parturient with spinal meningioma. AB - We report our experience with epidural anesthesia for cesarean section in a morbidly obese parturient with progressive paraplegia from a spinal meningioma. Epidural anesthesia may represent a safe anesthetic choice in such clinical situations. PMID- 22778680 TI - Breast metastasis from a melanoma. AB - Benign and primary malignant breast tumors are quite common, but secondary tumors in the breast from metastatic malignancies are rare. Nevertheless, metastasis to the breast must be considered in any patient with a known primary malignant tumor history who presents with a breast lump. We report a case of a premenopausal woman diagnosed with a metastatic melanoma in her breast. PMID- 22778681 TI - Fibrolipomatous hamartoma of the median nerve in the elbow: a case report. AB - A fibrolipomatous hamartoma-also known as a fibrofatty overgrowth, perineural lipoma, intraneural lipoma, and lipomatous hamartoma-is a rare, benign, congenital lesion most commonly found in the median nerve, usually at the level of the wrist or hand. To our knowledge, no published cases report a hamartoma arising from the median nerve at the level of the elbow. We report a case of a fibrolipomatous hamartoma in a 55-year-old woman that necessitated a surgical intervention because of its size and associated neurologic symptoms. PMID- 22778683 TI - Acute respiratory distress following ultrasound-guided supraclavicular block. AB - BACKGROUND: Brachial plexus blocks have become very common for patients undergoing upper extremity surgery. We report a case in which the patient developed ipsilateral phrenic nerve paralysis and acute respiratory failure following supraclavicular nerve block. CASE REPORT: A 61-year-old female diabetic, morbidly obese patient presented for a repeat debridement of necrotizing fasciitis on her left arm. She received a left-sided supraclavicular brachial plexus block. Within a few minutes, the patient began to experience acute dyspnea, anxiety, and oxygen saturation of 90%. Breath sounds were diminished in the left hemithorax. Arterial blood gases revealed evidence of acute respiratory acidosis. The chest x-ray was normal. After induction, we intubated the patient. Subsequent arterial blood gases showed marked improvement in respiratory acidosis. We believed left phrenic nerve paralysis to be the cause of the distress. The patient was extubated in the surgical intensive care unit the following day, and infusion of ropivacaine 0.2% was started. The catheter was removed afterward secondary to its occlusion. CONCLUSION: Phrenic nerve injury leading to respiratory distress is a rare complication of supraclavicular brachial plexus block. Anesthesiologists should be ready for emergency intubation when performing this kind of block. PMID- 22778682 TI - Pyoderma gangrenosum: a rare cause of breast ulceration. AB - Breast ulceration is an alarming sign for clinicians and places a significant physical and psychological burden on the patient. We report a rare presentation of pyoderma gangrenosum of the breast in a patient known to have ulcerative colitis but no active underlying disease process and no history of breast tissue trauma. This case report with literature review highlights the importance of considering pyoderma gangrenosum as a differential diagnosis in breast ulcers. PMID- 22778684 TI - Management of atrial tachycardia in the newborn with enterovirus myocarditis. AB - Neonatal enterovirus myocarditis is a rare but serious infection that is often an underrecognized cause of cardiovascular collapse. Enterovirus myocarditis in patients with such collapse should be suspected when signs of congestive heart failure and tachyarrhythmia are present. The majority of reported electrical disturbances associated with enterovirus myocarditis are ventricular in origin, but the infection can present as atrial tachyarrhythmia. Atrial tachyarrhythmias associated with enterovirus myocarditis are difficult to manage because of their resistance to conventional antiarrhythmic therapy. We present 2 cases of neonates with atrial tachycardia associated with enterovirus myocarditis who responded to a combination of amiodarone and flecainide. PMID- 22778685 TI - Relative afferent pupillary defect: an unusual manifestation of carotid artery dissection. AB - We report the case of a man with a carotid dissection who had relative afferent pupillary defect (RAPD) that persisted throughout his hospital course. Other causes for RAPD were quickly ruled out. Carotid dissections often have ophthalmic manifestations-including RAPD, which, although uncommon as a presenting sign, can be tested for with the swinging flashlight test. PMID- 22778687 TI - Letters to the editor. PMID- 22778686 TI - Bowel obstruction in a pregnant patient with a restorative proctocolectomy and ileoanal j-pouch: a case report. AB - A 24-year-old pregnant woman had a bowel obstruction secondary to a gravid uterus. A multispecialty team approach resulted in a restorative proctocolectomy, which led to resolution of acute symptoms and a successful pregnancy. PMID- 22778690 TI - CME Upcoming Events/CME Credit Information. PMID- 22778691 TI - CME Test/CME Application Form. PMID- 22778689 TI - Recent publications by ochsner authors. PMID- 22778693 TI - Intron Retention and TE Exonization Events in ZRANB2. AB - The Zinc finger, RAN-binding domain-containing protein 2 (ZRANB2), contains arginine/serine-rich (RS) domains that mediate its function in the regulation of alternative splicing. The ZRANB2 gene contains 2 LINE elements (L3b, Plat_L3) between the 9th and 10th exons. We identified the exonization event of a LINE element (Plat_L3). Using genomic PCR, RT-PCR amplification, and sequencing of primate DNA and RNA samples, we analyzed the evolutionary features of ZRANB2 transcripts. The results indicated that 2 of the LINE elements were integrated in human and all of the tested primate samples (hominoids: 3 species; Old World monkey: 8 species; New World monkey: 6 species; prosimian: 1 species). Human, rhesus monkey, crab-eating monkey, African-green monkey, and marmoset harbor the exon derived from LINE element (Plat_L3). RT-PCR amplification revealed the long transcripts and their differential expression patterns. Intriguingly, these long transcripts were abundantly expressed in Old World monkey lineages (rhesus, crab eating, and African-green monkeys) and were expressed via intron retention (IR). Thus, the ZRANB2 gene produces 3 transcript variants in which the Cterminus varies by transposable elements (TEs) exonization and IR mechanisms. Therefore, ZRANB2 is valuable for investigating the evolutionary mechanisms of TE exonization and IR during primate evolution. PMID- 22778694 TI - Internet addiction phenomenon in early adolescents in Hong Kong. AB - The present study investigated the prevalence and demographic correlates of Internet addiction in Hong Kong adolescents as well as the change in related behavior at two time points over a one-year interval. Two waves of data were collected from a large sample of students (Wave 1: 3,328 students, age = 12.59 +/ 0.74 years; Wave 2: 3,580 students, age = 13.50 +/- 0.75 years) at 28 secondary schools in Hong Kong. Comparable to findings at Wave 1 (26.4%), 26.7% of the participants met the criterion of Internet addiction at Wave 2 as measured by Young's 10-item Internet Addiction Test. The behavioral pattern of Internet addiction was basically stable over time. While the predictive effects of demographic variables including age, gender, family economic status, and immigration status were not significant, Internet addictive behaviors at Wave 1 significantly predicted similar behaviors at Wave 2. Students who met the criterion of Internet addiction at Wave 1 were 7.55 times more likely than other students to be classified as Internet addicts at Wave 2. These results suggest that early detection and intervention for Internet addiction should be carried out. PMID- 22778692 TI - Diversity of Eukaryotic Translational Initiation Factor eIF4E in Protists. AB - The greatest diversity of eukaryotic species is within the microbial eukaryotes, the protists, with plants and fungi/metazoa representing just two of the estimated seventy five lineages of eukaryotes. Protists are a diverse group characterized by unusual genome features and a wide range of genome sizes from 8.2 Mb in the apicomplexan parasite Babesia bovis to 112,000-220,050 Mb in the dinoflagellate Prorocentrum micans. Protists possess numerous cellular, molecular and biochemical traits not observed in "text-book" model organisms. These features challenge some of the concepts and assumptions about the regulation of gene expression in eukaryotes. Like multicellular eukaryotes, many protists encode multiple eIF4Es, but few functional studies have been undertaken except in parasitic species. An earlier phylogenetic analysis of protist eIF4Es indicated that they cannot be grouped within the three classes that describe eIF4E family members from multicellular organisms. Many more protist sequences are now available from which three clades can be recognized that are distinct from the plant/fungi/metazoan classes. Understanding of the protist eIF4Es will be facilitated as more sequences become available particularly for the under represented opisthokonts and amoebozoa. Similarly, a better understanding of eIF4Es within each clade will develop as more functional studies of protist eIF4Es are completed. PMID- 22778695 TI - Less is more? The impact of trauma volume on the positive rate of head computed tomography scans in head trauma patients. AB - OBJECTIVE: Few studies have assessed the impact of trauma volume on the operational efficiency of emergency departments. Herein, we evaluate the association between trauma volume with the positive rate of head computed tomography scans in head trauma patients in a tertiary care hospital. METHODS: This is a retrospective cohort review involving all head trauma patients presenting to a tertiary care hospital. Trauma census, head trauma patient volume, the number of emergent head CT scans, and the number of positive head CT scans were collected on a monthly basis. Comparison was primarily made between the trauma patient volume and the positive rate of head CT scans. RESULTS: 25,549 trauma patients were reviewed. Of these, 5,168 (20.2%) sustained head trauma and 3,336 head CT scans were performed with mean 29.1% positive rate of substantial head injuries. The monthly data were analyzed and a statistically significant correlation between monthly trauma volume and decrease in positive rate of head CT scan was identified (Pearson r = -0.51, P = 0.02). With introducing different cut-point values of trauma volume, we identified the threshold of trauma census as approximately 4.9 and 8.8% higher than mean monthly trauma volume in discriminating significant decrease of positive rate of head CT scans. PMID- 22778696 TI - Quantifying liver cirrhosis by extracting significant features from MRI T2 image. AB - Most patients with liver cirrhosis must undergo a series of clinical examinations, including ultrasound imaging, liver biopsy, and blood tests. However, the quantification of liver cirrhosis by extracting significant features from a T2-weighted magnetic resonance image (MRI) provides useful diagnostic information in clinical tests. Sixty-two subjects were randomly selected to participate in this retrospective analysis with assigned to experimental and control groups. The T2-weighted MRI was obtained and to them dynamic adjusted gray levels. The extracted features of the image were standard deviation (SD), mean, and entropy of pixel intensity in the region of interest (ROI). The receiver operator characteristic (ROC) curve, 95% confidence intervals, and kappa statistics were used to test the significance and agreement. The analysis of area under ROC shows that SD, mean, and entropy in the ROI were significant between the experimental group and the control group. Smaller values of SD, mean, and entropy were associated with a higher probability of liver cirrhosis. The agreements between the extracted features and diagnostic results were shown significantly (P < 0.001). In this investigation, quantitative features of SD, mean, and entropy in the ROI were successfully computed by the dynamic gray level scaling of T2-weighted MRI with high accuracy. PMID- 22778697 TI - Mixed sequence reader: a program for analyzing DNA sequences with heterozygous base calling. AB - The direct sequencing of PCR products generates heterozygous base-calling fluorescence chromatograms that are useful for identifying single-nucleotide polymorphisms (SNPs), insertion-deletions (indels), short tandem repeats (STRs), and paralogous genes. Indels and STRs can be easily detected using the currently available Indelligent or ShiftDetector programs, which do not search reference sequences. However, the detection of other genomic variants remains a challenge due to the lack of appropriate tools for heterozygous base-calling fluorescence chromatogram data analysis. In this study, we developed a free web-based program, Mixed Sequence Reader (MSR), which can directly analyze heterozygous base-calling fluorescence chromatogram data in .abi file format using comparisons with reference sequences. The heterozygous sequences are identified as two distinct sequences and aligned with reference sequences. Our results showed that MSR may be used to (i) physically locate indel and STR sequences and determine STR copy number by searching NCBI reference sequences; (ii) predict combinations of microsatellite patterns using the Federal Bureau of Investigation Combined DNA Index System (CODIS); (iii) determine human papilloma virus (HPV) genotypes by searching current viral databases in cases of double infections; (iv) estimate the copy number of paralogous genes, such as beta-defensin 4 (DEFB4) and its paralog HSPDP3. PMID- 22778698 TI - Consumption of pornographic materials among Hong Kong early adolescents: a replication. AB - Consumption of pornographic materials was examined in 3,638 secondary 2 students in Hong Kong. Results showed that over 80% of the respondents had never consumed pornographic materials in the past year. Internet pornography was the most common medium that adolescents used when viewing pornographic materials. Males reported a higher level of pornography consumption than did females. Participants who were born in mainland China were more likely to consume pornographic materials than their Hong Kong counterparts. Regardless of the types of pornographic materials, the levels of pornography consumption significantly increased over time. Results also showed that higher levels of positive youth development and better family functioning were concurrently related to a lower level of pornography consumption at secondary 2. The relative contribution of positive youth development and family factors to pornographic material consumption was also explored. PMID- 22778699 TI - Subcutaneous administration of tramadol after elective surgery is as effective as intravenous administration in relieving acute pain and inflammation in dogs. AB - Subcutaneous (SC) administration of tramadol was compared with intravenous (IV) administration to evaluate analgesia following canine ovariohysterectomy (OHE). Healthy female dogs (n = 12) between 1 and 3 years of age (1.95 +/- 0.65 years), weighing between 10.5 and 17.1 kg (13.12 +/- 1.95 kg), were used. Pain was assessed at baseline before surgery and then hourly for 8 hr after surgery. Tramadol was administered both SC and IV at a dose of 3 mg/kg and provided significant postoperative analgesia, as indicated by analgesiometry, beta endorphin levels, and interleukin 6 (IL-6) levels. The respiratory rates and rectal temperatures remained normal and were not significantly different between or within the groups. A significant increase in heart rate was observed at 4 hr for dogs in both groups relative to the baseline, but there was no significant difference in heart rates between the groups at any time point. A significant decrease in mechanical pain threshold was observed within each group after surgery, but both groups responded similarly, suggesting that SC administration of tramadol is as effective as IV administration. Increased serum levels of both IL-6 and beta-endorphin 3 hr postoperatively further indicate that both routes of administration achieve similar pain control. Thus, the relative analgesic efficacy of SC tramadol is comparable to that of IV administration and can be used to achieve similar effects for postsurgical pain management in dogs undergoing OHE. PMID- 22778701 TI - Critical period of weed control in aerobic rice. AB - Critical period of weed control is the foundation of integrated weed management and, hence, can be considered the first step to design weed control strategy. To determine critical period of weed control of aerobic rice, field trials were conducted during 2010/2011 at Universiti Putra Malaysia. A quantitative series of treatments comprising two components, (a) increasing duration of weed interference and (b) increasing length of weed-free period, were imposed. Critical period was determined through Logistic and Gompertz equations. Critical period varied between seasons; in main season, it started earlier and lasted longer, as compared to off-season. The onset of the critical period was found relatively stable between seasons, while the end was more variable. Critical period was determined as 7-49 days after seeding in off-season and 7-53 days in main season to achieve 95% of weed-free yield, and 23-40 days in off-season and 21-43 days in main season to achieve 90% of weed-free yield. Since 5% yield loss level is not practical from economic view point, a 10% yield loss may be considered excellent from economic view point. Therefore, aerobic rice should be kept weed-free during 21-43 days for better yield and higher economic return. PMID- 22778700 TI - Associations between pathological gambling and psychiatric comorbidity among help seeking populations in Hong Kong. AB - Problem gambling is complex and often comorbid with other mental health problems. Unfortunately, gambling studies on comorbid psychiatric disorders among Chinese communities are extremely limited. The objectives of this study were to (a) determine the prevalence of comorbid psychiatric disorders among treatment seeking pathological gamblers; (b) compare the demographic profiles and clinical features of pathological gamblers with and without comorbid psychiatric disorders; (c) explore the associations between pathological gambling and psychiatric disorders and their temporal relationship. Participants (N = 201) who sought gambling counseling were examined by making Axis-I diagnoses including mood disorders, schizophrenia spectrum disorders, substance use disorders, anxiety disorders, and adjustment disorder. Results showed that 63.7% of participants had lifetime comorbid psychiatric disorder. The most common comorbid psychiatric mental disorders were mood disorders, adjustment disorder, and substance use disorders. Pathological gamblers with psychiatric comorbidities were significantly more severe in psychopathology, psychosocial functioning impairment, and gambling problems than those without the disorders. PMID- 22778702 TI - Effects of hyperbaric oxygen on metabolic capacity of the skeletal muscle in type 2 diabetic rats with obesity. AB - We investigated whether hyperbaric oxygen enhances the oxidative metabolic capacity of the skeletal muscle and attenuates adipocyte hypertrophy in type 2 diabetic rats with obesity. Five-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats were used as diabetic animals and nondiabetic controls, respectively, and assigned to control and hyperbaric oxygen groups. Animals in the hyperbaric oxygen group were exposed to an atmospheric pressure of 1.25 with an oxygen concentration of 36% for 3 h daily. The glucose level at 27 weeks of age was significantly higher in OLETF rats than in LETO rats, but the elevation was inhibited in OLETF rats exposed to hyperbaric oxygen. The slow-to-fast fiber transition in the skeletal muscle was observed in OLETF rats, but the shift was inhibited in OLETF rats exposed to hyperbaric oxygen. Additionally, the oxidative enzyme activity of muscle fibers was increased by hyperbaric oxygen. The adipocyte size was larger in OLETF rats than in LETO rats, but hypertrophied adipocytes were not observed in OLETF rats exposed to hyperbaric oxygen. Hyperbaric oxygen enhances glucose and lipid metabolism in the skeletal muscle, indicating that hyperbaric oxygen can prevent elevation of glucose and adipocyte hypertrophy in diabetic rats with obesity. PMID- 22778703 TI - Characteristics, management, and in-hospital outcomes of diabetic patients with acute coronary syndrome in the United Arab Emirates. AB - We describe the baseline characteristics, management, and in-hospital outcomes of patients in the United Arab Emirates (UAE) with DM admitted with an acute coronary syndrome (ACS) and assess the influence of DM on in-hospital mortality. Data was analyzed from 1697 patients admitted to various hospitals in the UAE with a diagnosis of ACS in 2007 as part of the 1st Gulf RACE (Registry of Acute Coronary Events). Of 1697 patients enrolled, 668 (39.4%) were diabetics. Compared to patients without DM, diabetic patients were more likely to have a past history of coronary artery disease (49.1% versus 30.1%, P < 0.001), hypertension (67.2% versus 36%, P < 0.001), and prior revascularization (21% versus 11.4%, P < 0.001). They experienced more in-hospital recurrent ischemia (8.5% versus 5.1%; P = 0.004) and heart failure (20% versus 10%; P < 0.001). The mortality rate was 2.7% for diabetics and 1.6% for nondiabetics (P = 0.105). After age adjustment, in-hospital mortality increased by 3.5% per year of age (P = 0.016). This mortality was significantly higher in females than in males (P = 0.04). ACS patients with DM have different clinical characteristics and appear to have poorer outcomes. PMID- 22778704 TI - The association between single-nucleotide polymorphisms of ORAI1 gene and breast cancer in a Taiwanese population. AB - BACKGROUND: Breast cancer is the most common malignancy in women. There is increasing evidence suggesting that ORAI1, components of store-operated calcium channel, play a pivotal role in breast cancer progression and metastasis. METHODS: A total of 384 female patients with breast cancer were included in this study. We selected five representative tagging ORAI1 SNPs from HapMap database with minimum allele frequency (MAF) >10%. Genotyping was performed using TaqMan allelic discrimination assay. Chi-square (chi2) test was used to analyze statistical differences among control and patient groups in genotype and allelic frequencies. RESULTS: Two of the ORAI1 SNPs (rs12320939 and rs12313273) were associated with estrogen receptors positive in breast cancer patients under the recessive model. When the Bonferroni correction was performed, the significance still existed. In addition, rs12320939 also associated with the lymph nodal involvement. CONCLUSION: We showed that genetic polymorphisms of ORAI1 associated strongly with lymph nodal involvement and estrogen receptors (ERs) positive breast cancer patients in a Taiwanese population. PMID- 22778705 TI - Ki-67 and MCM-2 in dental follicle and odontogenic cysts: the effects of inflammation on proliferative markers. AB - The aim of this study was to investigate whether there is any association between inflammation and the expression of markers of cell cycle entry (Ki-67 and MCM-2) in dental follicle (DF) of asymptomatic impacted teeth and odontogenic cysts. The study consisted of 70 DFs and 20 odontogenic cysts (radicular cyst (RC), dentigerous cyst (DC) and keratocytic odontogenic tumor (KCOT) located at posterior mandibular region. Histological findings of inflammation for all specimen and mucous cell prosoplasia, squamous metaplasia, glandular epithelium for all DFs were stained with hematoxyline and eosin, periodic acid schiff, alcian blue, and mucin. Epithelial cell proliferation was determined by using immunohistochemical labeling for Ki-67 and MCM-2. The histologic examinations showed 16% mucous cell prosoplasia, 54% squamous metaplasia, 20% glandular epithelium, 37% inflammation. Inflammation was detected in all RCs and %62 in DF, %43 in DC and KCOT. Positive correlation was found between the inflammation of DF and odontogenic cysts (P < 0.01). The mean Ki-67 and MCM-2 expressions were found 9, 64 +/- 5, 99 and 6, 34 +/- 3, 81 in DF, 11, 85 +/- 9, 01 and 13, 6 +/- 9, 94 in odontogenic cysts, respectively. While the mean Ki-67 expressions were statistically significant in DF and KCOT (P < 0.01), MCM-2 were significant in RC and KCOT (P < 0.01). MCM-2 expresion in RCs were statistically significant than KCOT (P < 0.01). The results of this study indicated that the higher MCM-2 expressions in RC than the KCOT might be related to the inflammation and this protein might be more sensitive to inflammation. PMID- 22778706 TI - Management of depression: during pregnancy and the postpartum period. PMID- 22778707 TI - Efficacy and Safety of Once- versus Twice-Daily Carbamazepine Extended-Release Capsules for the Treatment of Manic Symptoms in Patients with Bipolar I Disorder. AB - OBJECTIVE: To compare the efficacy and safety of carbamazepine extended-release capsules (CBZ-ERC) administered twice daily (BID) versus once daily for the treatment of manic symptoms associated with bipolar I disorder in adults. DESIGN: This was a Phase IIIb, randomized, double-blind, parallel-group, multicenter, 12 week study. Subjects were randomized (1:1) to CBZ-ERC once daily at bedtime (QHS) or BID. Dosing was initiated at CBZ-ERC 200mg/d and titrated to achieve an optimal dose (target dose, 800mg/d; maximum dose, 1600mg/d). The primary efficacy outcome variable was the Young Mania Rating Scale (YMRS). The Hamilton Rating Scale for Depression, 21-item version (HAM-D(21)), Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions Scale-Bipolar Version (CGI-BP), and time to remission were secondary outcome variables. Safety measures included recording of adverse events, physical examination, vital signs (blood pressure, pulse rate, and weight), and clinical laboratory and electrocardiogram (ECG) parameters. RESULTS: BID and QHS dosing were equally effective in improving symptoms of bipolar disorder, as measured with the YMRS, HAM-D(21), MADRS, and CGI-BP. Both BID and QHS dosing significantly improved total scores on the YMRS, HAM-D(21), and MADRS at all time points without statistically significant differences between groups. All three components of the CGI-BP improved during the study, and a large percentage of subjects in both groups achieved remission without significant differences between groups. Both CBZ-ERC regimens appeared to be safe and well tolerated. CONCLUSION: These results suggest QHS dosing may be a safe and effective alternative to BID dosing of CBZ-ERC for treating manic episodes for many adults with bipolar I disorder, although additional studies are needed to confirm this finding. PMID- 22778709 TI - Civil commitment in the United States. AB - This article reviews the academic literature on the psychiatric practice of civil commitment. It provides an overview of the history of involuntary psychiatric hospitalization in the United States-from the creation of the first asylum and the era of institutionalization to the movement of deinstitutionalization. The ethical conflict that the practice of involuntary hospitalization presents for providers, namely the conflict between the ethical duties of beneficence and respect for patient autonomy, is presented. The evolution of the United States commitment standards, from being based on a right to treatment for patients with mental illness to being based on dangerousness, as well as the implications that the changes in commitment criteria has had on patients and society, are discussed. Involuntary hospitalization of patient populations that present unique challenges for psychiatry (e.g., not guilty by reason of insanity acquittees, sex offenders, and individuals with eating disorders, substance use disorders, and personality disorders) is discussed. Finally, an overview of outpatient commitment is provided. By reading this article, one will learn the history of involuntary psychiatric hospitalization in the United States and gain an understanding of the ethical issues that make civil commitment one of the most controversial practices in modern psychiatry. PMID- 22778710 TI - Cooking fuels and the push for cleaner alternatives: a case study from Burkina Faso. AB - INTRODUCTION: More than 95% of the population in Burkina Faso uses some form of solid biomass fuel. When these fuels are burned in traditional, inefficient stoves, pollutant levels within and outside the home can be very high. This can have important consequences for both health and climate change. Thus, the push to switch to cleaner burning fuels is advantageous. However, there are several considerations that need to be taken into account when considering the use and promotion of different fuel types. OBJECTIVE: In the setting of the semi-urban area of Nouna, Burkina Faso, we examine the common fuel types used (wood, charcoal and liquid petroleum gas (LPG)) in terms of consumption, energy, availability, air pollution and climate change. RESULTS AND CONCLUSION: Although biomass solid fuel does offer some advantages over LPG, the disadvantages make this option much less desirable. Lower energy efficiencies, higher pollutant emission levels, the associated health consequences and climate change effects favour the choice of LPG over solid biomass fuel use. Further studies specific to Burkina Faso, which are lacking in this region, should also be undertaken in this area to better inform policy decisions. PMID- 22778711 TI - Emerging PPARgamma-Independent Role of PPARgamma Ligands in Lung Diseases. AB - Peroxisome proliferator activated receptor (PPAR)-gamma is a nuclear hormone receptor that is activated by multiple agonists including thiazolidinediones, prostaglandins, and synthetic oleanolic acids. Many PPARgamma ligands are under investigation as potential therapies for human diseases. These ligands modulate multiple cellular pathways via both PPARgamma-dependent and PPARgamma-independent mechanisms. Here, we review the role of PPARgamma and PPARgamma ligands in lung disease, with emphasis on PPARgamma-independent effects. PPARgamma ligands show great promise in moderating lung inflammation, as antiproliferative agents in combination to enhance standard chemotherapy in lung cancer and as treatments for pulmonary fibrosis, a progressive fatal disease with no effective therapy. Some of these effects occur when PPARgamma is pharmaceutically antagonized or genetically PPARgamma and are thus independent of classical PPARgamma-dependent transcriptional control. Many PPARgamma ligands demonstrate direct binding to transcription factors and other proteins, altering their function and contributing to PPARgamma-independent inhibition of disease phenotypes. These PPARgamma-independent mechanisms are of significant interest because they suggest new therapeutic uses for currently approved drugs and because they can be used as probes to identify novel proteins and pathways involved in the pathogenesis or treatment of disease, which can then be targeted for further investigation and drug development. PMID- 22778712 TI - Neonatally induced mild diabetes in rats and its effect on maternal, placental, and fetal parameters. AB - The aim of this study was to assess placental changes and reproductive outcomes in neonatally induced mild diabetic dams and fetal development in their offspring. At birth, female rats were assigned either to control or diabetic group (100 mg of streptozotocin/Kg, subcutaneously). At adulthood, the female rats were mated. During pregnancy, the blood glucose levels and glucose and insulin tolerance tests were performed. At term, maternal reproductive outcomes, fetal and placental weight, and placental morphology were analyzed. Diabetic rats had smaller number of living fetuses, implantations and corpora lutea, and increased rate of embryonic loss. Placenta showed morphometric alterations in decidua area. Our results showed that mild diabetes was sufficient to trigger alterations in maternal organism leading to impaired decidua development contributing to failure in embryonic implantation and early embryonic losses. Regardless placental decidua alteration, the labyrinth, which is responsible for the maternal-fetal exchanges, showed no morphometric changes contributing to an appropriate fetal development, which was able to maintain normal fetal weight at term in mild diabetic rats. Thus, this experimental model of diabetes induction at the day of birth was more effective to reproduce the reproductive alterations of diabetic women. PMID- 22778713 TI - Topical application of Sadat-Habdan mesenchymal stimulating peptide (SHMSP) accelerates wound healing in diabetic rabbits. AB - OBJECTIVE: Diminished wound healing is a common problem in diabetic patients due to diminished angiogenesis. SHMSP was found to promote angiogenesis. The present study was carried out to examine the effect of this peptide in healing of wounds in diabetic rabbits. MATERIALS AND METHODS: Twenty male New Zealand rabbits were used in this study. Diabetes mellitus was induced and the rabbits were randomly divided into two equal groups: control group and peptide group. A-full thickness punch biopsy was made to create a wound of about 10 mm on the right ears of all rabbits. Every day, the wound was cleaned with saline in control groups. In the peptide group, 15 mg of SHMSP was applied after cleaning. On day 15th, all animals were sacrificed, and the wounds were excised with a rim of 5 mm of normal surrounding tissue. Histo-pathological assessment of wound healing, inflammatory cell infiltration, blood vessel proliferation, and collagen deposition was performed. RESULTS: There were no deaths among the groups. There was significant increase in wound healing, blood vessel proliferation and collagen deposition, and significant decrease in inflammatory cell infiltration in the peptide group compared to the control group. CONCLUSION: Topical application of SHMSP improves wound healing in diabetic rabbits. PMID- 22778714 TI - Diabetes and thyroid cancer risk: literature review. AB - Diabetic patients have a higher risk of various types of cancer. However, whether diabetes may increase the risk of thyroid cancer has not been extensively studied. This paper reviews and summarizes the current literature studying the relationship between diabetes mellitus and thyroid cancer, and the possible mechanisms linking such an association. Epidemiologic studies showed significant or nonsignificant increases in thyroid cancer risk in diabetic women and nonsignificant increase or no change in thyroid cancer risk in diabetic men. A recent pooled analysis, including 5 prospective studies from the USA, showed that the summary hazard ratio (95% confidence interval) for women was 1.19 (0.84-1.69) and was 0.96 (0.65-1.42) for men. Therefore, the results are controversial and the association between diabetes and thyroid cancer is probably weak. Further studies are necessary to confirm their relationship. Proposed mechanisms for such a possible link between diabetes and thyroid cancer include elevated levels of thyroid-stimulating hormone, insulin, glucose and triglycerides, insulin resistance, obesity, vitamin D deficiency, and antidiabetic medications such as insulin or sulfonylureas. PMID- 22778715 TI - Serum CA19-9 level associated with metabolic control and pancreatic beta cell function in diabetic patients. AB - CA19-9 is a tumor-associated antigen. It is also a marker of pancreatic tissue damage that might be caused by diabetes. Long-term poor glycemic control may lead to pancreatic beta cell dysfunction which is reflected by elevated serum CA19-9 level. Intracellular cholesterol accumulation leads to islet dysfunction and impaired insulin secretion which provide a new lipotoxic model. This study firstly found total cholesterol was one of the independent contributors to CA19 9. Elevated serum CA19-9 level in diabetic patients may indicate further investigations of glycemic control, pancreatic beta cell function, and total cholesterol level. PMID- 22778716 TI - A comparison of inflammatory and oxidative stress markers in adipose tissue from weight-matched obese male and female mice. AB - Expansion of intra-abdominal adipose tissue and the accompanying inflammatory response has been put forward as a unifying link between obesity and the development of chronic diseases. However, an apparent sexual dimorphism exists between obesity and chronic disease risk due to differences in the distribution and abundance of adipose tissue. A range of experimental protocols have been employed to demonstrate the role of estrogen in regulating health benefits; however, most studies are confounded by significant differences in body weight and adiposity. Therefore, the purpose of this study was to compare weight-matched obese male and female mice to determine if the sex-dependent health benefits remain when body weight is similar. The development of obesity in female mice receiving a high-fat diet was delayed; however, subsequent comparisons of weight matched obese mice revealed greater adiposity in obese female mice. Despite excess adiposity and enlarged adipocyte size, obese females remained more glucose tolerant than weight-matched male mice, and this benefit was associated with increased expression of adiponectin and reductions in immune cell infiltration and oxidative stress in adipose tissue. Therefore, the protective benefits of estrogen persist in the obese state and appear to improve the metabolic phenotype of adipose tissue and the individual. PMID- 22778717 TI - Transcriptional mechanisms controlling miR-375 gene expression in the pancreas. AB - MicroRNAs (miRNAs) are a class of small non-coding RNAs that play an important role in mediating a broad and expanding range of biological activities. miR-375 is expressed selectively in the pancreas. We have previously shown that selective expression of miR-375 in pancreatic beta cells is controlled by transcriptional mechanisms operating through a TATA box-containing promoter. Expression of miR 375 has been reported in non-beta cells within the endocrine pancreas, and indeed inactivation of miR-375 leads to perturbation in cell mass and number of both alpha and beta cells. Consistent with its expression throughout the endocrine pancreas, we now show that the promoter of the miR-375 gene shows selective activity in pancreatic endocrine alpha cells, comparable to that observed in beta cells. We previously identified a novel negative regulatory element located downstream of the miR-375 gene transcription start site. By generating luciferase reporter genes, we now show that the sequence is functional also when positioned upstream of a heterologous promoter, thus proving that the repressor effect is mediated at least in part at the level of transcription. Further characterization of the transcriptional control mechanism regulating expression of miR-375 and other pancreatic miRNAs will contribute to a better understanding of pancreas development and function. PMID- 22778718 TI - Protective effects of salivary factors in dental caries in diabetic patients of Pakistan. AB - Salivary factors have been studied for their effects on the process of dental caries in patients of diabetes mellitus type 2. In this study, protective role of salivary pH, salivary flow rate, and salivary calcium is assessed in the patients of diabetes mellitus type 2 with dental caries. The samples of saliva were collected from 400 patients of diabetes mellitus type 2 and 300 age- and sex- matched controls after getting informed consent. All the subjects were classified into four groups according to age. The severity of dental caries was counted by decayed, missed, and filled teeth (DMFT) score. The salivary pH, flow rate, and calcium levels were found to be low in patients as compared to controls. The levels of fasting blood sugar, HbA1c, and DMFT score were found to be significantly high in patients than controls. The glycemic factors were significantly correlated with salivary factors indicating their influence on progression of caries in diabetes. On the basis of findings, it is concluded that the suitable salivary pH and flow rate may be regarded as main protective factors against dental caries in diabetes. Optimum level of salivary calcium may be responsible for continuous supply of calcium to arrest the demineralization and help reduce the occurrence of dental caries. PMID- 22778719 TI - Shine on: Review of Laser- and Light-Based Therapies for the Treatment of Burn Scars. AB - Restoration of form and function after burn injury remains challenging, but emerging laser and pulsed light technologies now offer hope for patients with hypertrophic scars, which may be associated with persistent hyperemia, chronic folliculitis, intense pruritis, and neuropathic pain. In addition to impairing body image, these scars may limit functional recovery, compromise activities of daily living, and prevent return to work. Three different platforms are now poised to alter our reconstructive algorithm: (1) vascular-specific pulsed dye laser (PDL) to reduce hyperemia, (2) ablative fractional CO(2) laser to improve texture and pliability of the burn scar, and (3) intense pulsed light (IPL) to correct burn scar dyschromia and alleviate chronic folliculitis. In this paper, we will provide an overview of our work in this area, which includes a systematic review, a retrospective analysis of our preliminary experience, and interim data from our on-going, prospective, before-after cohort trial. We will demonstrate that laser- and light-based therapies can be combined with each other safely to yield superior results, often at lower cost, by reducing the need for reconstructive surgery. Modulating the burn scar, through minimally invasive modalities, may replace conventional methods of burn scar excision and yield outcomes not previously possible or conceivable. PMID- 22778720 TI - Psychological issues in inflammatory bowel disease: an overview. AB - Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) is a chronic and disabling disease with unknown etiology. There have been some controversies regarding the role of psychological factors in the course of IBD. The purpose of this paper is to review that role. First the evidence on role of stress is reviewed focusing on perceived stress and patients' beliefs about it in triggering or exacerbating the course of IBD. The possible mechanisms by which stress could be translated into IBD symptoms, including changes in motor, sensory and secretory gastrointestinal function, increase intestinal permeability, and changes in the immune system are, then reviewed. The role of patients' concerns about psychological distress and their adjustment to disease, poor coping strategies, and some personality traits that are commonly associated with these diseases are introduced. The prevalence rate, the timing of onset, and the impact of anxiety and depression on health-related quality of life are then reviewed. Finally issues about illness behavior and the necessity of integrating psychological interventions with conventional treatment protocols are explained. PMID- 22778721 TI - Culture Method and PCR for the Detection of Helicobacter pylori in Drinking Water in Basrah Governorate Iraq. AB - Helicobacter pylori is recognized by the World Health Organization to be the primary cause of peptic ulcers, chronic gastritis, and stomach cancer, though the source of human infection is not well understood. One of the problems in understanding the source of human contamination is the difficulty in isolating the organism from the environment. However, the combination of PCR results with those of culturing of 471 drinking water samples can provide a more accurate picture of H. pylori detection. In this method 78 presumptive H. pylori colonies out of 266 tap water samples were obtained in the preliminary detection on modified Columbia agar (MCUA) slant relying on urease positivity with a rate of 29.3%. However, only 11 out of them were confirmed by Gram staining and biochemical tests reducing the rate to 4.13% whereas only 3 (1.46%) from 205 reverse osmosis (RO) water samples. Furthermore, only 6 (54.5%) out of the 11 isolates from tap water and 1 (33.3%) of the 3 RO isolates were confirmed by 16SrRNA PCR. Thus PCR confirmation reduced the rate to 2.2%. In addition, only 4 (4%) of 100 tap water samples negative for H. pylori by culture method were H. pylori positive by 16SrRNA. Water samples were collected from 24 districts of Basrah Governorate from February-December 2009. The direct recovery of H. pylori from drinking water is both alarming and scientifically exciting in terms of the investigation of its epidemiology. PMID- 22778722 TI - Pharmacokinetics of the perioperative use of cancer chemotherapy in peritoneal surface malignancy patients. AB - Background. The peritoneal surface is an acknowledged locoregional failure site of abdominal malignancies. Previous treatment attempts with medical therapy alone did not result in long-term survival. During the last two decades, new treatment protocols combining cytoreductive surgery with perioperative intraperitoneal and intravenous cancer chemotherapy have demonstrated very encouraging clinical results. This paper aims to clarify the pharmacologic base underlying these treatment regimens. Materials and Methods. A review of the current pharmacologic data regarding these perioperative chemotherapy protocols was undertaken. Conclusions. There is a clear pharmacokinetic and pharmacodynamic rationale for perioperative intraperitoneal and intravenous cancer chemotherapy in peritoneal surface malignancy patients. PMID- 22778723 TI - Helicobacter pylori Eradication Therapies in the Era of Increasing Antibiotic Resistance: A Paradigm Shift to Improved Efficacy. AB - With the rising prevalence of antimicrobial resistance, the eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing to unacceptable levels (i.e., <=80%) in most countries. After these disappointing results, several authorities have proposed that infection with H. pylori should be approached and treated as any other bacterial infectious disease. This implicates that clinicians should prescribe empirical treatments yielding a per protocol eradication of at least 90%. In recent years several treatments producing >=90% cure rates have been proposed including sequential therapy, concomitant quadruple therapy, hybrid (dual-concomitant) therapy, and bismuth containing quadruple therapy. These treatments are likely to represent the recommended first-line treatments in the near future. In the present paper, we are considering a series of critical issues regarding currently available means and approaches for the management of H. pylori infection. Clinical needs and realistic endpoints are taken into account. Furthermore, emerging strategies for the eradication of H. pylori and the existing evidence of their clinical validation and widespread applicability are discussed. PMID- 22778724 TI - Morbidity and mortality outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a single institution in Japan. AB - Background. Even though cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are associated with a high morbidity and mortality rates, it has been reported that CRS and HIPEC improved survival of selected patients with peritoneal carcinomatosis. We aimed to report morbidity and mortality results of CRS and HIPEC from a single institution in Japan. Methods and Results. Total of 284 procedures of CRS were performed on patients with pseudomyxoma peritonei, peritoneal carcinomatosis (PC) from colon cancer and gastric cancer between 2007 and 2011 in our institution. The morbidity rate was 49% of all procedure, and grades I/II and grades III/IV complications were 28% and 17%, respectively. Most frequent complication was surgical site infections including intraabdominal abscess. The mortality rate was 3.5%, and reoperation was needed in 11% of all procedures. Univariate and multivariate analysis showed peritoneal carcinomatosis index (PCI) greater than 20 was the only significant factor for occurrence of postoperative complications (P < 0.01). In contrast, HIPEC significantly reduced postoperative complications (P < 0.05). Conclusions. The morbidity and mortality rates of our institution are comparable with previous reports that are in acceptable rates. Optimal patient selection such as patients with PCI less than 20 seems to be of paramount importance to CRS and HIPEC. PMID- 22778726 TI - Proximal hypospadias repair outcomes in patients with a specific disorder of sexual development diagnosis. AB - Boys with undermasculinized external genital and/or 46,XY disorders of sex development (DSD) often receive masculinizing genitoplasty. Such procedures are done to correct ventral curvature of the phallus, reposition a proximally located urethral meatus, and cosmetically correct the appearance of labioscrotal folds. No studies to date have assessed if patients with a specific DSD diagnosis have worse outcomes for severe proximal hypospadias procedures or whether or not these patients require more extensive surgical maneuvers than severe proximal hypospadias patients without a specific DSD diagnosis. We retrospectively reviewed consecutive proximal hypospadias repairs performed at our institution from 1998 to 2010 and compared the anatomy, surgical technique required for repair, and outcomes in patients with and without a definitive DSD diagnosis. Boys with a specific DSD diagnosis do have significantly more atypical anatomy when undergoing proximal hypospadias masculinizing genitoplasties. They are more likely to require associated gonad procedures but do not have an increased risk of complications or number of surgeries when compared to other proximal hypospadias patients without a specific DSD diagnosis. The risk of complications is consistent with reports in the literature, and the mean number of procedures in this contemporary study is fewer than in historic reports. PMID- 22778727 TI - Comparison of Spinal Block Levels between Laboring and Nonlaboring Parturients Using Combined Spinal Epidural Technique with Intrathecal Plain Bupivacaine. AB - Background. It was suggested that labor may influence the spread of intrathecal bupivacaine using combined spinal epidural (CSE) technique. However, no previous studies investigated this proposition. We designed this study to investigate the spinal block characteristics of plain bupivacaine between nonlaboring and laboring parturients using CSE technique. Methods. Twenty-five nonlaboring (Group NL) and twenty-five laboring parturients (Group L) undergoing cesarean delivery were enrolled. Following identification of the epidural space at the L3-4 interspace, plain bupivacaine 10 mg was administered intrathecally using CSE technique. The level of sensory block, degree of motor block, and hemodynamic changes were assessed. Results. The baseline systolic blood pressure (SBP) and the maximal decrease of SBP in Group L were significantly higher than those in Group NL (P = 0.002 and P = 0.03, resp.). The median sensory level tested by cold stimulation was T6 for Group NL and T5 for Group L (P = 0.46). The median sensory level tested by pinprick was T7 for both groups (P = 0.35). The degree of motor block was comparable between the two groups (P = 0.85). Conclusion. We did not detect significant differences in the sensory block levels between laboring and nonlaboring parturients using CSE technique with intrathecal plain bupivacaine. PMID- 22778725 TI - Bladder Cancer Immunotherapy: BCG and Beyond. AB - Mycobacterium bovis bacillus Calmette-Guerin (BCG) has become the predominant conservative treatment for nonmuscle invasive bladder cancer. Its mechanism of action continues to be defined but has been shown to involve a T helper type 1 (Th1) immunomodulatory response. While BCG treatment is the current standard of care, a significant proportion of patients fails or do not tolerate treatment. Therefore, many efforts have been made to identify other intravesical and immunomodulating therapeutics to use alone or in conjunction with BCG. This paper reviews the progress of basic science and clinical experience with several immunotherapeutic agents including IFN-alpha, IL-2, IL-12, and IL-10. PMID- 22778728 TI - Evaluation of the GlideScope Direct: A New Video Laryngoscope for Teaching Direct Laryngoscopy. AB - Background. Teaching direct laryngoscopy is limited by the inability of the instructor to simultaneously view the airway with the laryngoscopist. Our primary aim is to report our initial use of the GlideScope Direct, a video-enabled, Macintosh laryngoscope intended primarily as a training tool in direct laryngoscopy. Methods. The GlideScope Direct was made available to anyone who planned on performing direct laryngoscopy as the primary technique for intubation. Novices were those who had performed <30 intubations. Results. The GlideScope Direct was used 123 times as primarily a direct laryngoscope while the instructor viewed the intubation on the monitor. It was highly successful as a direct laryngoscope (93% success). Salvage by indirect laryngoscopy occurred in 7/9 remaining patients without changing equipment. Novices performed 28 intubations (overall success rate of 79%). In 6 patients, the instructor took over and successfully intubated the patient. Instructors used the video images to guide the operator in 16 (57%) of those patients. Seven different instructors supervised the 28 novices, all of who subjectively felt advantaged by having the laryngoscopic view available. Conclusions. The GlideScope Direct functions similarly to a Macintosh laryngoscope and provides the instructor subjective reassurance, while providing the ability to guide the trainee laryngoscopist. PMID- 22778729 TI - Glycopeptide resistance in gram-positive cocci: a review. AB - Vancomycin-resistant enterococci (VRE) have emerged as important nosocomial pathogens in the past two decades all over the world and have seriously limited the choices available to clinicians for treating infections caused by these agents. Methicillin-resistant Staphylococcus aureus, perhaps the most notorious among the nosocomial pathogens, was till recently susceptible to vancomycin and the other glycopeptides. Emergence of vancomycin nonsusceptible strains of S. aureus has led to a worrisome scenario where the options available for treating serious infections due to these organisms are very limited and not well evaluated. Vancomycin resistance in clinically significant isolates of coagulase negative staphylococci is also on the rise in many setups. This paper aims to highlight the genetic basis of vancomycin resistance in Enterococcus species and S. aureus. It also focuses on important considerations in detection of vancomycin resistance in these gram-positive bacteria. The problem of glycopeptide resistance in clinical isolates of coagulase-negative staphylococci and the phenomenon of vancomycin tolerance seen in some strains of Streptococcus pneumoniae has also been discussed. Finally, therapeutic options available and being developed against these pathogens have also found a mention. PMID- 22778730 TI - Literature retrieval and mining in bioinformatics: state of the art and challenges. AB - The world has widely changed in terms of communicating, acquiring, and storing information. Hundreds of millions of people are involved in information retrieval tasks on a daily basis, in particular while using a Web search engine or searching their e-mail, making such field the dominant form of information access, overtaking traditional database-style searching. How to handle this huge amount of information has now become a challenging issue. In this paper, after recalling the main topics concerning information retrieval, we present a survey on the main works on literature retrieval and mining in bioinformatics. While claiming that information retrieval approaches are useful in bioinformatics tasks, we discuss some challenges aimed at showing the effectiveness of these approaches applied therein. PMID- 22778731 TI - Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity. AB - Aims. 3,5,4'-Trihydroxy-trans-stilbene, a natural polyphenolic compound present in wine and grapes and better known as resveratrol, has free radical scavenging properties and is a potent protector against oxidative stress induced by alcohol metabolism. Today, the mechanism by which ethanol exerts its toxicity is still not well understood, but it is generally considered that free radical generation plays an important role in the appearance of structural and functional alterations in cells. The aim of this study was to evaluate the protective action of resveratrol against ethanol-induced brain cell injury. Methods. Primary cultures of rat astrocytes were exposed to ethanol, with or without a pretreatment with resveratrol. We examined the dose-dependent effects of this resveratrol pretreatment on cytotoxicity and genotoxicity induced by ethanol. Cytotoxicity was assessed using the MTT reduction test. Genotoxicity was evidenced using single cell gel electrophoresis. In addition, DNA staining with fluorescent dyes allowed visualization of nuclear damage using confocal microscopy. Results. Cell pretreatment with low concentrations of trans resveratrol (0.1-10 MUM) slowed down cell death and DNA damage induced by ethanol exposure, while higher concentrations (50-100 MUM) enhanced these same effects. No protection by cis-resveratrol was observed. Conclusion. Protection offered by trans-resveratrol against ethanol-induced neurotoxicity was only effective for low concentrations of this polyphenol. PMID- 22778732 TI - The Correlation between the CLEC16A Gene and Genetic Susceptibility to Type 1 Diabetes in Chinese Children. AB - Objective. The CLEC16A gene is related to the genetic susceptibility to T1DM with racial variability. This study investigated the association between CLEC16A gene polymorphisms and T1DM in Chinese children. Methods. 131 Chinese children with T1DM were selected for study, and 121 healthy adult blood donors were selected as normal controls. PCR and mass spectrometry was used to study the distributions of 17 CLEC16A alleles in patients and controls. The relationship between CLEC16A gene polymorphisms and T1DM was studied. Results. The distributions of two polymorphisms (rs12921922, rs12931878) of CLEC16A in T1DM and healthy controls were significantly different, while the distributions of other CLEC16A polymorphisms show no significant differences. The alleles of rs12921922 are C and T. The frequency of the T allele was significantly increased in patients versus healthy controls. The alleles of rs12931878 are A and C. The frequencies of the A allele are significantly increased in T1DM patients versus healthy controls. Conclusion. Two polymorphisms in the CLEC16A gene correlate with increased susceptibility to T1DM in Chinese children, revealing that it was another new gene that correlates with susceptibility to T1DM in multiple populations. PMID- 22778733 TI - Diamel therapy in polycystic ovary syndrome reduces hyperinsulinaemia, insulin resistance, and hyperandrogenaemia. AB - For to determine the effect of Diamel on the insulin resistance, insulin sensitivity, and sexual hormones results in women with polycystic ovary syndrome (PCOS). A study was carried out on 37 patients with this disorder. A triple-blind clinical trial was designed in which the Diamel food supplement was compared with a placebo. The women with reproductive ages were randomly distributed in two groups, with 18 and 19 women respectively, and they took Diamel or placebo and were followed up during 6 months with clinical and biochemical evaluation. A significant decrease in the HOMA-IR from the initial value at six months was observed in the group with Diamel. The insulin sensitivity improved considerably in this group. The rate of menstrual recovery was higher in the group with Diamel, and two patients from this group obtained pregnancy. The hormone levels shows a significant decrease in testosterone at 3 months in the group with Diamel compared with the control group. The LH also decreases in the same group when comparing the start with 6 months.We concluded that the Diamel decreases insulin resistance and improves sensitivity to this hormone in women with PCOS, with improvement in the levels of LH and testosterone. PMID- 22778734 TI - Bone mineral density in thalassemia major patients from antalya, Turkey. AB - Aim. We assessed the bone mineral density and related parameters in nine adults, thirty-eight pubertal, prepubertal totally forty-seven patients with thalassemia major living in Antalya, Turkey. Materials and Methods. We measured height and pubertal staging in last five years by six-month intervals. Average ferritin and hemoglobin concentrations were calculated for last three years. The levels of hydroxyproline, calcium, phosphorus, and creatinine were measured in 24 h urine, and those of parathormone, IGF 1, osteocalcine, alkaline phosphatase, calcium, ionized calcium, magnesium, phosphorus, creatine, blood glucose, thyroid stimulating hormone, alanine transaminase, and aspartate transaminase were determined in serum, and also the bone mineral density was measured. Results. The average L1-L4 bone mass density was 27.1 +/- 10.1 g cm(-2); the average bone mineral content was 0.65 +/- 0.11 g. of the patients with a Z-score under 2.5. A moderate relationship was found between the bone mass density age and height. Subjects in low pubertal staging and short stature (<3% percentile) have significantly lower bone mass densities P < 0.001. Conclusion. he prevalence of osteoporosis is high in patients with thalassemia major, possibly related to delayed puberty. PMID- 22778735 TI - Antiepidermal growth factor receptor therapy in squamous cell carcinoma of the head and neck. AB - Squamous cell carcinoma of head and neck (SCCHN) is the most common neoplasm of the upper aerodigestive tract. In this paper, we attempt to summarize the role and applications of the epidermal growth factor receptor (EGFR) inhibitors monoclonal antibodies (moAbs) and tyrosine kinase inhibitors (TKIs) locally advanced as well as metastatic SCCHN. Targeted therapy in SCCHN is now incorporated in the first-line regimes for advanced disease. Novel targeted agents, including the EGFR antibody, cetuximab, have been approved for use as single agents or in combination with radiation therapy or chemotherapy in treatment of recurrent metastatic or locally advanced SCCHN. Refractory mechanisms that bypass the pathway of EGFR inhibitors activity are identified explaining resistance to targeted therapy. Strategies of cotargeting EGFR and other pathways are under investigation. Examples of targeted therapy being used include mammalian target of rapamycin (mtor) inhibitors, antivascular endothelial growth factor (VEGF) moAb, and other inhibitors. We will be focusing our paper on the preclinical and clinical aspects of EGFR inhibition in SCCHN and touch upon other targeted therapies in application. PMID- 22778736 TI - Thymidine kinase 1 upregulation is an early event in breast tumor formation. AB - Prognostic markers play an important role in our understanding of tumors and how to treat them. Thymidine kinase 1 (TK1), a proliferation marker involved in DNA repair, has been shown to have independent prognostic potential. This prognostic potential includes the novel concept that upregulation of serum TK1 levels is an early event in cancer development. This same effect may also be seen in tumor tissue. In order to demonstrate that TK1 upregulation is an early event in tumor tissue formation, tissue arrays were obtained and stained for TK1 by immunohistochemistry. Using a progressive breast tissue array, precancerous tissue including breast adenosis, simple hyperplasia, and atypical hyperplasia stained positive for TK1 expression. Different stages of breast carcinoma tissue also stained positive for TK1 including nonspecific infiltrating duct, infiltrating lobular, and infiltrating duct with lymph node metastasis carcinomas. This indicates that TK1 upregulation is an early event in breast carcinoma development, and may be useful in identifying precancerous tissue. Further work is needed to better understand the differences seen between TK1 positive and negative tissues. PMID- 22778737 TI - Laser welding and syncristallization techniques comparison: in vitro study. AB - Background. Laser welding was first reported in 1967 and for many years it has been used in dental laboratories with several advantages versus the conventional technique. Authors described, in previous works, the possibility of using also chair-side Nd : YAG laser device (Fotona Fidelis III, lambda = 1064 nm) for welding metallic parts of prosthetic appliances directly in the dental office, extra- and also intra-orally. Syncristallisation is a soldering technique based on the creation of an electric arc between two electrodes and used to connect implants to bars intra-orally. Aim. The aim of this study was to compare two different laser welding devices with a soldering machine, all of these used in prosthetic dentistry. Material and Methods. In-lab Nd : YAG laser welding (group A = 12 samples), chair-side Nd : YAG laser welding (group B = 12 samples), and electrowelder (group C = 12 samples) were used. The tests were performed on 36 CrCoMo plates and the analysis consisted in evaluation, by microscopic observation, of the number of fissures in welded areas of groups A and B and in measurement of the welding strength in all the groups. The results were statistically analysed by means of one-way ANOVA and Tukey-Kramer multiple comparison tests. Results. The means and standard deviations for the number of fissures in welded areas were 8.12 +/- 2.59 for group A and 5.20 +/- 1.38 for group B. The difference was statistical significant (P = 0.0023 at the level 95%). On the other hand, the means and standard deviations for the traction tests were 1185.50 +/- 288.56 N for group A, 896.41 +/- 120.84 N for group B, and 283.58 +/- 84.98 N for group C. The difference was statistical significant (P = 0.01 at the level 95%). Conclusion. The joint obtained by welding devices had a significant higher strength compared with that obtained by the electrowelder, and the comparison between the two laser devices used demonstrated that the chair side Nd : YAG, even giving a lower strength to the joints, produced the lowest number of fissures in the welded area. PMID- 22778739 TI - Free Radical Production in Immune Cell Systems Induced by Ti, Ti6Al4V and SS Assessed by Chemiluminescence Probe Pholasin Assay. AB - The oxidative burst of human blood cells in the presence of different metal materials was investigated using chemiluminescence assay. Commercial pure titanium (Ti), titanium alloy (Ti6Al4V), and stainless steel 316L (SS) in particulate form with <20 MUm in size were used. The effect of particulate materials opsonisation on the upregulation of the respiratory burst production by blood cells was also assessed. The largest chemiluminescence response was achieved after simultaneous injection of the stimulants fMLP+PMA. Moreover, Ti and SS induced a greater inflammatory reaction compared to Ti6Al4V, since the respiratory burst mounted was higher for both materials after opsonisation treatment. These results suggest that in vitro chemiluminescence response and respiratory burst measurements proved to be composition and treatment dependent. PMID- 22778738 TI - Live Cells as Dynamic Laboratories: Time Lapse Raman Spectral Microscopy of Nanoparticles with Both IgE Targeting and pH-Sensing Functions. AB - This review captures the use of live cells as dynamic microlaboratories through implementation of labeled nanoparticles (nanosensors) that have both sensing and targeting functions. The addition of 2,4-epsilon-dinitrophenol-L-lysine (DNP) as a FcepsilonRI targeting ligand and 4-mercaptopyridine (4-MPy) as a pH-sensing ligand enables spatial and temporal monitoring of FcepsilonRI receptors and their pH environment within the endocytic pathway. To ensure reliability, the sensor is calibrated in vivo using the ionophore nigericin and standard buffer solutions to equilibrate the external [H(+)] concentration with that of the cell compartments. This review highlights the nanosensors, ability to traffic and respond to pH of receptor-bound nanosensors (1) at physiological temperature (37 degrees C) versus room temperature (25 degrees C), (2) after pharmacological treatment with bafilomycin, an H(+) ATPase pump inhibitor, or amiloride, an inhibitor of Na(+)/H(+) exchange, and (3) in response to both temperature and pharmacological treatment. Whole-cell, time lapse images are demonstrated to show the ability to transform live cells into dynamic laboratories to monitor temporal and spatial endosomal pH. The versatility of these probes shows promise for future applications relevant to intracellular trafficking and intelligent drug design. PMID- 22778740 TI - Assessment of the Quality of Newly Formed Bone around Titanium Alloy Implants by Using X-Ray Photoelectron Spectroscopy. AB - The aim of this study was to evaluate differences in bones quality between newly formed bone and cortical bone formed around titanium alloy implants by using X ray photoelectron spectroscopy. As a result of narrow scan measurement at 4 weeks, the newly formed bone of C1s, P2p, O1s, and Ca2p were observed at a different peak range and strength compared with a cortical bone. At 8 weeks, the peak range and strength of newly formed bone were similar to those of cortical bone at C1s, P2p, and Ca2p, but not O1s. The results from this analysis indicate that the peaks and quantities of each element of newly formed bone were similar to those of cortical bone at 8 weeks, suggestive of a strong physicochemical resemblance. PMID- 22778742 TI - Pharmacological Characterization of the Mechanisms Involved in Delayed Calcium Deregulation in SH-SY5Y Cells Challenged with Methadone. AB - Previously, we have shown that SH-SY5Y cells exposed to high concentrations of methadone died due to a necrotic-like cell death mechanism related to delayed calcium deregulation (DCD). In this study, we show that, in terms of their Ca(2+) responses to 0.5 mM methadone, SH-SY5Y cells can be pooled into four different groups. In a broad pharmacological survey, the relevance of different Ca(2+) related mechanisms on methadone-induced DCD was investigated including extracellular calcium, L-type Ca(2+) channels, MU-opioid receptor, mitochondrial inner membrane potential, mitochondrial ATP synthesis, mitochondrial Ca(2+)/2Na(+)-exchanger, reactive oxygen species, and mitochondrial permeability transition. Only those compounds targeting mitochondria such as oligomycin, FCCP, CGP 37157, and cyclosporine A were able to amend methadone-induced Ca(2+) dyshomeostasis suggesting that methadone induces DCD by modulating the ability of mitochondria to handle Ca(2+). Consistently, mitochondria became dramatically shorter and rounder in the presence of methadone. Furthermore, analysis of oxygen uptake by isolated rat liver mitochondria suggested that methadone affected mitochondrial Ca(2+) uptake in a respiratory substrate-dependent way. We conclude that methadone causes failure of intracellular Ca(2+) homeostasis, and this effect is associated with morphological and functional changes of mitochondria. Likely, this mechanism contributes to degenerative side effects associated with methadone treatment. PMID- 22778741 TI - Endothelial cells and astrocytes: a concerto en duo in ischemic pathophysiology. AB - The neurovascular/gliovascular unit has recently gained increased attention in cerebral ischemic research, especially regarding the cellular and molecular changes that occur in astrocytes and endothelial cells. In this paper we summarize the recent knowledge of these changes in association with edema formation, interactions with the basal lamina, and blood-brain barrier dysfunctions. We also review the involvement of astrocytes and endothelial cells with recombinant tissue plasminogen activator, which is the only FDA-approved thrombolytic drug after stroke. However, it has a narrow therapeutic time window and serious clinical side effects. Lastly, we provide alternative therapeutic targets for future ischemia drug developments such as peroxisome proliferator- activated receptors and inhibitors of the c-Jun N-terminal kinase pathway. Targeting the neurovascular unit to protect the blood-brain barrier instead of a classical neuron-centric approach in the development of neuroprotective drugs may result in improved clinical outcomes after stroke. PMID- 22778743 TI - Pathological significance of mitochondrial glycation. AB - Glycation, the nonenzymatic glycosylation of biomolecules, is commonly observed in diabetes and ageing. Reactive dicarbonyl species such as methylglyoxal and glyoxal are thought to be major physiological precursors of glycation. Because these dicarbonyls tend to be formed intracellularly, the levels of advanced glycation end products on cellular proteins are higher than on extracellular ones. The formation of glycation adducts within cells can have severe functional consequences such as inhibition of protein activity and promotion of DNA mutations. Although several lines of evidence suggest that there are specific mitochondrial targets of glycation, and mitochondrial dysfunction itself has been implicated in disease and ageing, it is unclear if glycation of biomolecules specifically within mitochondria induces dysfunction and contributes to disease pathology. We discuss here the possibility that mitochondrial glycation contributes to disease, focussing on diabetes, ageing, cancer, and neurodegeneration, and highlight the current limitations in our understanding of the pathological significance of mitochondrial glycation. PMID- 22778744 TI - Histocompatibility and hematopoietic transplantation in the zebrafish. AB - The zebrafish has proven to be an excellent model for human disease, particularly hematopoietic diseases, since these fish make similar types of blood cells as humans and other mammals. The genetic program that regulates the development and differentiation of hematopoietic cells is highly conserved. Hematopoietic stem cells (HSCs) are the source of all the blood cells needed by an organism during its lifetime. Identifying an HSC requires a functional assay, namely, a transplantation assay consisting of multilineage engraftment of a recipient and subsequent serial transplant recipients. In the past decade, several types of hematopoietic transplant assays have been developed in the zebrafish. An understanding of the major histocompatibility complex (MHC) genes in the zebrafish has lagged behind transplantation experiments, limiting the ability to perform unbiased competitive transplantation assays. This paper summarizes the different hematopoietic transplantation experiments performed in the zebrafish, both with and without immunologic matching, and discusses future directions for this powerful experimental model of human blood diseases. PMID- 22778747 TI - Antimicrobial peptides as therapeutic agents. PMID- 22778746 TI - Zebrafish thrombocytes: functions and origins. AB - Platelets play an important role in mammalian hemostasis. Thrombocytes of early vertebrates are functionally equivalent to mammalian platelets. A substantial amount of research has been done to study platelet function in humans as well as in animal models. However, to date only limited functional genomic studies of platelets have been performed but are low throughput and are not cost-effective. Keeping this in mind we introduced zebrafish, a vertebrate genetic model to study platelet function. We characterized zebrafish thrombocytes and established functional assays study not only their hemostatic function but to also their production. We identified a few genes which play a role in their function and production. Since we introduced the zebrafish model for the study of hemostasis and thrombosis, other groups have adapted this model to study genes that are associated with thrombocyte function and a few novel genes have also been identified. Furthermore, transgenic zebrafish with GFP-tagged thrombocytes have been developed which helped to study the production of thrombocytes and their precursors as well as their functional roles not only in hemostasis but also hematopoiesis. This paper integrates the information available on zebrafish thrombocyte function and its formation. PMID- 22778745 TI - In vivo chemical screening for modulators of hematopoiesis and hematological diseases. AB - In vivo chemical screening is a broadly applicable approach not only for dissecting genetic pathways governing hematopoiesis and hematological diseases, but also for finding critical components in those pathways that may be pharmacologically modulated. Both high-throughput chemical screening and facile detection of blood-cell-related phenotypes are feasible in embryonic/larval zebrafish. Two recent studies utilizing phenotypic chemical screens in zebrafish have identified several compounds that promote hematopoietic stem cell formation and reverse the hematopoietic phenotypes of a leukemia oncogene, respectively. These studies illustrate efficient drug discovery processes in zebrafish and reveal novel biological roles of prostaglandin E2 in hematopoietic and leukemia stem cells. Furthermore, the compounds discovered in zebrafish screens have become promising therapeutic candidates against leukemia and included in a clinical trial for enhancing hematopoietic stem cells during hematopoietic cell transplantation. PMID- 22778748 TI - Hyperfractionated radiotherapy with concurrent cisplatin/5-Fluorouracil for locoregional advanced head and neck cancer: analysis of 105 consecutive patients. AB - Objective. We reviewed a cohort of patients with previously untreated locoregional advanced head and neck squamous cell carcinoma (HNSCC) who received a uniform chemoradiotherapy regimen. Methods. Retrospective review was performed of 105 patients with stage III or IV HNSCC treated at Greater Baltimore Medical Center from 2000 to 2007. Radiation included 125 cGy twice daily for a total 70 Gy to the primary site. Chemotherapy consisted of cisplatin (12 mg/m(2)/h) daily for five days and 5-fluorouracil (600 mg/m(2)/20 h) daily for five days, given with weeks one and six of radiation. All but seven patients with N2 or greater disease received planned neck dissection after chemoradiotherapy. Primary outcomes were overall survival (OS), locoregional control (LRC), and disease-free survival (DFS). Results. Median followup of surviving patients was 57.6 months. Five-year OS was 60%, LRC was 68%, and DFS was 56%. Predictors of increased mortality included age >=55, female gender, hypopharyngeal primary, and T3/T4 stage. Twelve patients developed locoregional recurrences, and 16 patients developed distant metastases. Eighteen second primary malignancies were diagnosed in 17 patients. Conclusions. The CRT regimen resulted in favorable outcomes. However, locoregional and distant recurrences cause significant mortality and highlight the need for more effective therapies to prevent and manage these events. PMID- 22778749 TI - Dynamic change of intestinal duplication in an adult patient: a case report and literature review. AB - Intestinal duplication in an adult is an uncommon congenital abnormality because only minority of cases present in adulthood. More than 80% of cases occur before the age of two years as an acute abdomen, bowel obstruction or other complications associated with it. Duplication has two types, either cystic or tubular. Here, we report a case of an adult who was diagnosed preoperatively on CT scan as tubular intestinal duplication. CT images showed change in the morphology of the cystic mass after one week of antibiotics administration. On histopathological analysis, the resected duplicated segment had esophageal epithelium in addition to the intestinal gland. So far, we found no report describing CT findings of dynamic change of ileal duplication in the English literatures. PMID- 22778750 TI - Cardiac myxoma presenting as dyspnea after cesarean delivery. AB - Introduction. Dyspnea during pregnancy and in the immediate postpartum or postoperative period is a relatively common symptom that can be an early sign of a life threatening condition. The differential diagnosis is broad and can represent a wide variety of underlying etiologies. Cardiac tumors are one of the rarest causes of dyspnea in a reproductive age women during the postpartum period. Case Presentation. 42-years old G(7)P(1051) presented with acute dyspnea postoperatively after an elected uncomplicated repeat cesarean section and tubal ligation. The patient was diagnosed with a large left atrial cardiac myxoma and required urgent cardiothoracic surgery. Conclusion. The following case illustrates how a standard response to a common postpartum symptom, dyspnea, can divert and distract from less common exam findings. A careful, stepwise evaluation of symptoms and related findings will usually determine the underlying cause so that appropriate and timely treatment can be initiated. PMID- 22778751 TI - Rituximab-induced bronchiolitis obliterans organizing pneumonia. AB - Rituximab-induced lung disease (R-ILD) is a rare entity that should be considered in patients treated with rituximab who present with dyspnea, fever, and cough, but no clear evidence of infection. A variety of pathologic findings have been described in this setting. Bronchiolitis obliterans organizing pneumonia (BOOP) is the most common clinicopathologic diagnosis, followed by interstitial pneumonitis, acute respiratory distress syndrome (ARDS), and hypersensitivity pneumonitis. Prompt diagnosis and treatment with corticosteroids are essential as discussed by Wagner et al. (2007). Here we present a case of an 82-year-old man who was treated with rituximab for recurrent marginal zone lymphoma. After the first infusion of rituximab, he reported fever, chills, and dyspnea. On computed tomography imaging, he was found to have bilateral patchy infiltrates, consistent with BOOP on biopsy. In our patient, BOOP was caused by single-agent rituximab, in the first week after the first infusion of rituximab. We reviewed the relevant literature to clarify the different presentations and characteristics of R-ILD and raise awareness of this relatively overlooked entity. PMID- 22778752 TI - Desmoid tumor of the anterior abdominal wall in female patients: comparison with endometriosis. AB - In female patients presenting a tumor of the lower abdominal wall especially after cesarian section, an endometriotic tumor as well as an aggressive desmoid tumor should be considered. Symptoms in correlation with the monthly period can facilitate the presurgical differentiation between endometriosis and fibromatosis. Ultrasound reveals the typical location of both tumors and its remarkable sonographic appearance. In the clinical practice, the desmoid fibromatosis of the lower abdominal wall is a very rare disease. We present a case of a 25-year-old pregnant and discuss diagnostic and therapeutic options by a PubMed literature review. With the knowledge of the prognosis of the desmoid fibromatosis and the respective treatment options including wait and see, complete surgical resection with macroscopically free margins and adjuvant approaches is essential to avoid further interventions and progression of the locally destructive tumor. PMID- 22778753 TI - Rapid Recovery from Chronic PRCA by MSC Infusion in Patient after Major ABO Mismatched alloSCT. AB - Pure red cell aplasia (PRCA) is a rare complication in recipients of allogenic stem cell from ABO incompatible donors. It is characterized by reticulocytopenia and by an absence of red cell cell precursors in the bone marrow. Despite close isohemagglutinins monitoring and standard immunosupressive treatment in these patients prolong PRCA are still associated with severe transfusion dependence. We report the case of a 31 yr old male patient who underwent HLA-matched ABO mismatched allo-SCT and developed resistance PRCA despite conventional immunosupressive therapy and prophylaxis cotrasplantation of bone marrow derived MSC at day 0. He responded dramatically to therapy with adipose tissue derived mesenchymal stem cells from HSC donors and continued to be transfusion independent and AML-disease free. This method of the PRCA therapy of deserves further investigation. PMID- 22778754 TI - The comparition of the efficacy of two different probiotics in rotavirus gastroenteritis in children. AB - Objectives. The aim of the study is to compare the clinical effectiveness of the probiotics-Saccharomyces boulardii and Bifidobacterium lactis-in children who had been diagnosed with rotavirus gastroenteritis. Materials and methods. Seventy five patients aged between 5 months-5 years diagnosed as rotavirus gastroenteritis were included in the study. The patients diagnosed as rotavirus gastroenteritis by latex agglutination test in stool were divided into 3 groups of twenty-five patients each: First group was given oral rehydration therapy and rapid refeeding with a normal diet with Saccharomyces boulardii (spp. I-745), second group was given oral rehydration therapy and rapid refeeding with a normal diet with Bifidobacterium lactis (spp. B94, culture number:N degrees 118529) and third group received only oral rehydration therapy and rapid refeeding with a normal diet. Results. The duration of diarrhea was shorter in the group given oral rehydration therapy and rapid refeeding with a normal diet with Bifidobacterium lactis and Saccharomyces boulardii than the group given only oral rehydration therapy and rapid refeeding with a normal diet. Conclusion. Bifidobacterium lactis has a complemental role in the treatment of rotavirus gatroenteritis and other probiotics may also have a beneficial effect in rotavirus gastroenteritis compared with the therapy included only oral rehydration therapy and rapid refeeding with a normal diet. PMID- 22778755 TI - Arterial structure and function in ambulatory adolescents with cerebral palsy are not different from healthy controls. AB - Physical inactivity in youth with cerebral palsy (CP) places them at increased risk of developing cardiovascular disease. The current study assessed indices of arterial health in adolescents with CP, classified as levels I-II of the Gross Motor Function Classification System (GMFCS) (n = 11, age 13.2 +/- 2.1 yr), in comparison to age- and sex-matched controls (n = 11, age 12.4 +/- 2.3 yr). Groups were similar in anthropometric measurements, resting blood pressures, and heart rates. There were no group differences in brachial flow-mediated dilation (11.1 +/- 7.8 versus 6.1 +/- 3.6), carotid intima-media thickness (0.42 +/- 0.04 versus 0.41 +/- 0.03 mm), and distensibility (0.008 +/- 0.002 versus 0.008 +/- 0.002 mmHg) or central (4.3 +/- 0.6 versus 4.1 +/- 0.9 m/s) and peripheral pulse wave velocity (7.1 +/- 1.7 versus 7.6 +/- 1.1 m/s); CP versus healthy controls, respectively. Vigorous intensity physical activity (PA) was lower in the CP group (CP: 38 +/- 80 min versus controls: 196 +/- 174 min); groups were similar in light and moderate intensity PA levels. Arterial health of ambulatory youth with CP is not different from a control group despite lower vigorous PA levels. Similar studies need to examine individuals with more pronounced mobility limitations (GMFCS level III-V). PMID- 22778756 TI - The grasp reflex and moro reflex in infants: hierarchy of primitive reflex responses. AB - The plantar grasp reflex is of great clinical significance, especially in terms of the detection of spasticity. The palmar grasp reflex also has diagnostic significance. This grasp reflex of the hands and feet is mediated by a spinal reflex mechanism, which appears to be under the regulatory control of nonprimary motor areas through the spinal interneurons. This reflex in human infants can be regarded as a rudiment of phylogenetic function. The absence of the Moro reflex during the neonatal period and early infancy is highly diagnostic, indicating a variety of compromised conditions. The center of the reflex is probably in the lower region of the pons to the medulla. The phylogenetic meaning of the reflex remains unclear. However, the hierarchical interrelation among these primitive reflexes seems to be essential for the arboreal life of monkey newborns, and the possible role of the Moro reflex in these newborns was discussed in relation to the interrelationship. PMID- 22778757 TI - A New Bottle Design Decreases Hypoxemic Episodes during Feeding in Preterm Infants. AB - Oxygen saturation is lower during bottle feeding than during breastfeeding in preterm infants. Our objective was to compare two different bottle systems in healthy preterm infants before discharge in terms of SpO(2) and oral feeding efficiency (rate of milk intake). Infants without supplement oxygen needs were evaluated twice on the same day during two consecutive feeds, by the same nurse. Infants served as their own controls for comparison of two systems of bottles, the order of which was randomized. The new bottle's nipple design mimics mom's breast in shape and feel, and the bottle vents to air when the child sucks on the nipple. The other system was the hospital's standard plastic bottle with silicone nipple. The rate of milk intake was calculated as the total volume transferred minus volume lost divided by time of feeding, mL/min. Thirty-four infants (BW: 1, 163 +/- 479.1 g) were studied at 35.4 +/- 1.3 weeks after-conception. SpO(2) was significantly higher in infants fed with the new bottle design. Milk intake rate was significantly higher with the new bottle than with the standard bottle design. The new bottle design improves oral feeding performance in preterm infants near to discharge when compared to that of a standard bottle. PMID- 22778758 TI - A review of the potential for cardiometabolic dysfunction in youth with spina bifida and the role for physical activity and structured exercise. AB - Children and adolescents who have decreased mobility due to spina bifida may be at increased risk for the components of metabolic syndrome, including abdominal obesity, insulin resistance, and dyslipidemia due to low physical activity. Like their nondisabled peers, adolescents with spina bifida that develop metabolic risk factors early in life have set the stage for adult disease. Exercise interventions can improve metabolic dysfunction in nondisabled youth, but the types of exercise programs that are most effective and the mechanisms involved are not known. This is especially true in adolescents with spina bifida, who have impaired mobility and physical function and with whom there have been few well controlled studies. This paper highlights the current lack of knowledge about the role of physical activity and the need to develop exercise strategies targeting the reduction of cardiometabolic risk and improving quality of life in youth with spina bifida. PMID- 22778759 TI - Association of indoor smoke-free air laws with hospital admissions for acute myocardial infarction and stroke in three states. AB - OBJECTIVE: To examine whether comprehensive smoke-free air laws enacted in Florida, New York, and Oregon are associated with reductions in hospital admissions for acute myocardial infarction (AMI) and stroke. METHODS: Analyzed trends in county-level, age-adjusted, hospital admission rates for AMI and stroke from 1990 to 2006 (quarterly) for Florida, 1995 to 2006 (monthly) for New York, and 1998 to 2006 (monthly) for Oregon to identify any association between admission rates and passage of comprehensive smoke-free air laws. Interrupted time series analysis was used to adjust for the effects of preexisting moderate local-level laws, seasonal variation in hospital admissions, differences across counties, and a secular time trend. RESULTS: More than 3 years after passage of statewide comprehensive smoke-free air laws, rates of hospitalization for AMI were reduced by 18.4% (95% CI: 8.8-28.0%) in Florida and 15.5% (95% CI: 11.0 20.1%) in New York. Rates of hospitalization for stroke were reduced by 18.1% (95% CI: 9.3-30.0%) in Florida. The few local comprehensive laws in Oregon were not associated with reductions in AMI or stroke statewide. CONCLUSION: Comprehensive smoke-free air laws are an effective policy tool for reducing the burden of AMI and stroke. PMID- 22778760 TI - Towards curative cancer immunotherapy: overcoming posttherapy tumor escape. AB - The past decade has witnessed the evolvement of cancer immunotherapy as an increasingly effective therapeutic modality, evidenced by the approval of two immune-based products by the FDA, that is, the cancer vaccine Provenge (sipuleucel-T) for prostate cancer and the antagonist antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4) ipilimumab for advanced melanoma. In addition, the clinical evaluations of a variety of promising immunotherapy drugs are well under way. Benefiting from more efficacious immunotherapeutic agents and treatment strategies, a number of recent clinical studies have achieved unprecedented therapeutic outcomes in some patients with certain types of cancers. Despite these advances, however, the efficacy of most cancer immunotherapies currently under clinical development has been modest. A recurring scenario is that therapeutic maneuvers initially led to measurable antitumor immune responses in cancer patients but ultimately failed to improve patient outcomes. It is increasingly recognized that tumor cells can antagonize therapy induced immune attacks through a variety of counterregulation mechanisms, which represent a fundamental barrier to the success of cancer immunotherapy. Herein we summarize the findings from some recent preclinical and clinical studies, focusing on how tumor cells advance their survival and expansion by hijacking therapy-induced immune effector mechanisms that would otherwise mediate their destruction. PMID- 22778761 TI - Clinical isolates of Mycobacterium tuberculosis differ in their ability to induce respiratory burst and apoptosis in neutrophils as a possible mechanism of immune escape. AB - Tuberculosis pathogenesis was earlier thought to be mainly related to the host but now it appears to be clear that bacterial factors are also involved. Genetic variability of Mycobacterium tuberculosis (Mtb) could be slight but it may lead to sharp phenotypic differences. We have previously reported that nonopsonized Mtb H37Rv induce apoptosis of polymorphonuclear neutrophils (PMNs) by a mechanism that involves the p38 pathway. Here we evaluated the capability to induce PMN apoptosis of two prevalent Mtb lineages in Argentina, the Latin America and Mediterranean (LAM), and Haarlem, using the H37Rv as a reference strain. Results showed that LAM strains strongly induced apoptosis of PMN which correlated with the induction of reactive oxygen species (ROS) production and p38 activation. Interestingly, the highly prosperous multidrug-resistant M strain, belonging to the Haarlem lineage, lacked the ability to activate and to induce PMN apoptosis as a consequence of (1) a weak ROS production and (2) the contribution of antiapoptotic mechanisms mediated at least by ERK. Although with less skill, M is able to enter the PMN so that phenotypic differences could lead PMN to be a reservoir allowing some pathogens to prevail and persist over other strains in the community. PMID- 22778762 TI - The expression of selected proapoptotic molecules in dermatitis herpetiformis. AB - The role of the process of apoptosis is investigated in the pathogenesis of many autoimmune diseases; however at present, there is not much information about its role in dermatitis herpetiformis. Skin biopsies were taken from 18 DH patients and from 10 healthy subjects. The localization and expression of Bax, Fas, FasL, TRAIL, TRAIL-R in skin lesions, and perilesional skin were studied by immunohistochemistry. Expression of Bax, Fas, and Fas ligand was detected in the keratinocytes in skin biopsies from DH patients. Expression of TRAIL and TRAIL receptor was confirmed in epidermis, infiltration cells, and some fibroblasts. The expression of examined molecules in biopsies from healthy people was observed only in single cells. There were statistically significant differences between lesional, perilesional, and healthy skin of control group in Bax expression analysis and between lesional skin and control group in Fas, FasL, and TRAIL expression. There were statistically significant differences between control group and perilesional skin in Bax and FasL expression. Our results show that selected proapoptotic molecules may take part in pathogenesis of dermatitis herpetiformis, but the role of apoptosis in this process is not clear. PMID- 22778763 TI - Dermatitis herpetiformis: from the genetics to the development of skin lesions. AB - Dermatitis herpetiformis (DH) is a rare autoimmune disease linked to gluten sensitivity with a chronic-relapsing course. It is currently considered to be the specific cutaneous manifestation of celiac disease (CD). Both conditions are mediated by the IgA class of autoantibodies, and the diagnosis of DH is dependent on the detection of granular deposits of IgA in the skin. There is an underlying genetic predisposition to the development of DH, but environmental factors are also important. This paper describes these different factors and discusses the known mechanism that lead to the development of skin lesions. PMID- 22778764 TI - Pulmonary immune-compartment-specific interferon gamma responses in HIV-infected individuals with active tuberculosis (TB) in an area of high TB prevalence. AB - There is a paucity of data on the pulmonary immune-compartment interferon gamma (IFNgamma) response to M. tuberculosis, particularly in settings of high tuberculosis (TB) prevalence and in HIV-coinfected individuals. This data is necessary to understand the diagnostic potential of commercially available interferon gamma release assays (IGRAs) in both the pulmonary immune-compartment and peripheral blood. We used intracellular cytokine staining by flow cytometry to assess the IFNgamma response to purified protein derivative (PPD) and early secretory antigen 6 (ESAT6) in induced sputa (ISp) and blood samples from HIV infected, smear-negative, TB suspects. We found that individuals with active TB disease produced significantly less IFNgamma in response to PPD in their induced sputa samples than individuals with non-active TB (control group). This difference was not reflected in the peripheral blood, even within the CD27- CD4+ memory T lymphocyte population. These findings suggest that progression to active TB disease may be associated with the loss of IFNgamma secretion at the site of primary infection. Our findings highlight the importance of studying pulmonary immune-compartment M. tuberculosis specific responses to elucidate IFNgamma secretion across the spectrum of TB disease. PMID- 22778765 TI - Distinct characteristics in Japanese dermatitis herpetiformis: a review of all 91 Japanese patients over the last 35 years. AB - We reviewed all 91 Japanese dermatitis herpetiformis (DH) patients reported over the last 35 years. The male-to-female ratio was 2 : 1. The mean age at onset was 43.8, and 13 years earlier for female patients. More than half of these Japanese DH patients showed granular IgA deposition in the papillary dermis, and another one-third showed fibrillar IgA deposition. The male patients with granular IgA deposition were 10 years older than those with fibrillar deposition. Whereas patients with granular IgA deposition showed typical distribution of the skin lesions, the predilection sites of DH tended to be spared in patients with fibrillar IgA deposition. Only 3 patients had definite gluten-sensitive enteropathy. There was a statistical difference in the frequency of human leukocyte antigen (HLA)-DR9 between the granular group and controls among Japanese. No patients had HLA-DQ2 or -DQ8, which is frequently found in Caucasian DH patients. The absence of HLA-DQ2/DQ8, the inability to identify celiac disease in most cases, the predominance of fibrillar IgA, and the unusual distribution of clinical lesions in Japanese patients suggest that Japanese DH may be a subset of DH patients and have a pathogenesis which is different from that currently proposed in Caucasian DH patients. PMID- 22778766 TI - Novel anti-melanoma immunotherapies: disarming tumor escape mechanisms. AB - The immune system fights cancer and sometimes temporarily eliminates it or reaches an equilibrium stage of tumor growth. However, continuous immunological pressure also selects poorly immunogenic tumor variants that eventually escape the immune control system. Here, we focus on metastatic melanoma, a highly immunogenic tumor, and on anti-melanoma immunotherapies, which recently, especially following the FDA approval of Ipilimumab, gained interest from drug development companies. We describe new immunomodulatory approaches currently in the development pipeline, focus on the novel CEACAM1 immune checkpoint, and compare its potential to the extensively described targets, CTLA4 and PD1. This paper combines multi-disciplinary approaches and describes anti-melanoma immunotherapies from molecular, medical, and business angles. PMID- 22778767 TI - New roads open up for implementing immunotherapy in mesothelioma. AB - Treatment options for malignant mesothelioma are limited, and the results with conventional therapies have been rather disappointing to this date. Chemotherapy is the only evidence-based treatment for mesothelioma patients in good clinical condition, with an increase in median survival of only 2 months. Therefore, there is urgent need for a different approach to battle this malignancy. As chronic inflammation precedes mesothelioma, the immune system plays a key role in the initiation of this type of tumour. Also, many immunological cell types can be found within the tumour at different stages of the disease. However, mesothelioma cells can evade the surveillance capacity of the immune system. They build a protective tumour microenvironment to harness themselves against the immune system's attacks, in which they even abuse immune cells to act against the antitumour immune response. In our opinion, modulating the immune system simultaneously with the targeting of mesothelioma tumour cells might prove to be a superior treatment. However, this strategy is challenging since the tumour microenvironment possesses numerous forms of defence strategies. In this paper, we will discuss the interplay between immunological cells that can either inhibit or stimulate tumour growth and the challenges associated with immunotherapy. We will provide possible strategies and discuss opportunities to overcome these problems. PMID- 22778769 TI - Involvement of Heme Oxygenase-1 Participates in Anti-Inflammatory and Analgesic Effects of Aqueous Extract of Hibiscus taiwanensis. AB - Anti-inflammatory effects of the aqueous extract of Hibiscus taiwanensis (AHT) were used in lipopolysaccharide (LPS-)stimulated mouse macrophage RAW264.7 cells and carrageenan (Carr-)induced mouse paw edema model. When RAW264.7 macrophages were treated with AHT together with LPS, a concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-alpha), and prostaglandin E2 (PGE(2)) levels productions were detected. Western blotting revealed that AHT blocked protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and elevated heme oxygenase-1 (HO-1), significantly. In the animal test, AHT decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated AHT decreased the NO, TNF-alpha, and PGE2 levels on the serum level at the 5th h after the Carr injection. Western blotting revealed that AHT decreased Carr-induced iNOS, and COX-2, and increased HO-1 expressions at the 5th h in the edema paw. These findings demonstrated that AHT has excellent anti inflammatory activities in vitro and in vivo and thus it has great potential to be used as a source for natural health products. PMID- 22778770 TI - Norcantharidin Induces HL-60 Cells Apoptosis In Vitro. AB - Norcantharidin (NCTD) is the demethylated form of cantharidin, which is the active substance of mylabris, and is known to have anticancer potentials. The aim of this paper was to assess the apoptosis-inducing effect of NCTD on HL-60 cells. Methods. The effects of NCTD were detected by flow cytometer on the cell toxicity, cell cycle, and apoptosis of HL-60 cells cultured in vitro. Results. After 48-hour treatment with NCTD, the growth of HL-60 cells was inhibited significantly. The summit of apoptosis appeared after 24 hours. The percentage of the cells in G(1) phase decreased and then increased in S and G(2)+ M phase, while the S and G(2)+ M phases were blocked after treatment with 5, 10, and 50 MUmol/L NCTD for 24 hours. Conclusions. NCTD can induce the apoptosis of HL-60 cells and inhibit the fissiparism, and the domino effect was obviously correlated with the time and dosage. PMID- 22778768 TI - Macrophages in tumor microenvironments and the progression of tumors. AB - Macrophages are widely distributed innate immune cells that play indispensable roles in the innate and adaptive immune response to pathogens and in-tissue homeostasis. Macrophages can be activated by a variety of stimuli and polarized to functionally different phenotypes. Two distinct subsets of macrophages have been proposed, including classically activated (M1) and alternatively activated (M2) macrophages. M1 macrophages express a series of proinflammatory cytokines, chemokines, and effector molecules, such as IL-12, IL-23, TNF-alpha, iNOS and MHCI/II. In contrast, M2 macrophages express a wide array of anti-inflammatory molecules, such as IL-10, TGF-beta, and arginase1. In most tumors, the infiltrated macrophages are considered to be of the M2 phenotype, which provides an immunosuppressive microenvironment for tumor growth. Furthermore, tumor associated macrophages secrete many cytokines, chemokines, and proteases, which promote tumor angiogenesis, growth, metastasis, and immunosuppression. Recently, it was also found that tumor-associated macrophages interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. So mediating macrophage to resist tumors is considered to be potential therapy. PMID- 22778771 TI - Temperature and safety profiles of needle-warming techniques in acupuncture and moxibustion. AB - The needle-warming technique combines acupuncture and moxibustion, and it is commonly practised in China to relieve pain conditions. However, burning of moxa has many disadvantages. This study examined the temperature and safety profiles of such technique. First, skin temperature changes during needle-warming were examined in anesthetized animals to determine the safe distance for needle warming moxibustion in human subjects. Then, the practical distance for needle warming in human subjects were verified. Finally, the temperature profiles of the needle during needle-warming moxibustion were examined using an infrared camera. Our results show that during needle-warming moxibustion there is little heat being conducted into deep tissue via the shaft of the needle, and that the effective heating time to the acupoint is rather short compared to the period of moxibustion. These findings suggest that the needle-warming technique is an inefficient way of acupoint thermal stimulation and should be modified and improved using new technologies. PMID- 22778772 TI - Evaluation of the effects of acupuncture on blood flow in humans with ultrasound color Doppler imaging. AB - Color Doppler imaging (CDI) can be used to noninvasively create images of human blood vessels and quantitatively evaluate blood flow in real-time. The purpose of this study was to assess the effects of acupuncture on the blood flow of the peripheral, mesenteric, and retrobulbar arteries by CDI. Statistical significance was defined as P values less than 0.05. Blood flow in the radial and brachial arteries was significantly lower during needle stimulation on LR3 than before in healthy volunteers, but was significantly higher after needle stimulation than before. LR3 stimulation also resulted in a significant decrease in the vascular resistance of the short posterior ciliary artery and no significant change of blood flow through the superior mesenteric artery (SMA) during acupuncture. In contrast, ST36 stimulation resulted in a significant increase in blood flow through the SMA and no significant change in the vascular resistance of the retrobulbar arteries. Additionally, acupuncture at previously determined acupoints in patients with open-angle glaucoma led to a significant reduction in the vascular resistance of the central retinal artery and short posterior ciliary artery. Our results suggest that acupuncture can affect blood flow of the peripheral, mesenteric, and retrobulbar arteries, and CDI can be useful to evaluate hemodynamic changes by acupuncture. PMID- 22778773 TI - Anti-infective and antiproliferative potential of african medicinal plants. PMID- 22778774 TI - The Effects of Clinical Hypnosis versus Neurolinguistic Programming (NLP) before External Cephalic Version (ECV): A Prospective Off-Centre Randomised, Double Blind, Controlled Trial. AB - Objective. To examine the effects of clinical hypnosis versus NLP intervention on the success rate of ECV procedures in comparison to a control group. Methods. A prospective off-centre randomised trial of a clinical hypnosis intervention against NLP of women with a singleton breech fetus at or after 37(0/7) (259 days) weeks of gestation and normal amniotic fluid index. All 80 participants heard a 20-minute recorded intervention via head phones. Main outcome assessed was success rate of ECV. The intervention groups were compared with a control group with standard medical care alone (n = 122). Results. A total of 42 women, who received a hypnosis intervention prior to ECV, had a 40.5% (n = 17), successful ECV, whereas 38 women, who received NLP, had a 44.7% (n = 17) successful ECV (P > 0.05). The control group had similar patient characteristics compared to the intervention groups (P > 0.05). In the control group (n = 122) 27.3% (n = 33) had a statistically significant lower successful ECV procedure than NLP (P = 0.05) and hypnosis and NLP (P = 0.03). Conclusions. These findings suggest that prior clinical hypnosis and NLP have similar success rates of ECV procedures and are both superior to standard medical care alone. PMID- 22778775 TI - The Quintessence of Traditional Chinese Medicine: Syndrome and Its Distribution among Advanced Cancer Patients with Constipation. AB - Constipation is a common problem in advanced cancer patients; however, specific clinical guidelines on traditional Chinese medicine (TCM) syndrome (Zhang) are not yet available. In this cross-sectional study, the TCM syndromes distribution and their common symptoms and signs among 225 constipated advanced cancer patients were determined. Results showed that 127 patients (56.4%) and 7 patients (3.1%) were in deficient and excessive patterns, respectively, while 91 patients (40.4%) were in deficiency-excess complex. The distributions of the five syndromes were: Qi deficiency (93.3%), Qi stagnation (40.0%), blood (Yin) deficiency (28.9%), Yang deficiency (22.2%), and excess heat (5.8%). Furthermore, age, functional status, and level of blood haemoglobin were factors related to the type of TCM syndrome. A TCM prescription with the functions on replenishing the Deficiency, redirecting the flow of Qi stagnation and moistening the dryness caused by the blood (Yin) deficiency can be made for the treatment of advance cancer patients with constipation. Robust trials are urgently needed for further justifying its efficacy and safety in evidence-based approaches. PMID- 22778776 TI - Traditional chinese medicine in cancer care: a review of case series published in the chinese literature. AB - Traditional Chinese medicine (TCM) has been widely used in cancer in China. Case series report a series of cases exposed to a certain intervention. To understand the current situation of case series of TCM for cancer, we performed this review. We included case series of cancer patients treated with TCM therapy. Electronic searches were conducted in four main Chinese databases until February 2011. A total of 1,217 reports of case series (92,945 patients) were included. The top five types of cancer were lung cancer, liver cancer, stomach cancer, leukemia, and esophageal cancer. Leukopenia and hiccup treated by TCM were the most common adverse reactions after surgery or induced by chemo/radiotherapy. More than half of the patients were treated with TCM therapies alone. The application of herbal medicines especially formula based on syndrome differentiation was highly prevalent, and the typical administration route was oral usage. 1,182 reports were published in a structured format. The quantity of TCM case series for cancer treatment is substantial. Further studies should focus on the most common types of cancer and the most frequently applied TCM therapies. We presented a recommendation from the methodological point of view for the format of reporting. PMID- 22778777 TI - Herbal Formula, PM014, Attenuates Lung Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease. AB - Chronic obstructive pulmonary disease (COPD), which is characterized by airway obstruction, leads to, as the two major forms of COPD, chronic bronchitis and emphysema. This study was conducted to evaluate the effects of herbal formula, PM014, in a murine model of COPD. Balb/c mice were treated once with each herb extract in PM014 or PM014 mixture via an oral injection. Lipopolysaccharide (LPS) or elastase/LPS were administrated to the mice to induce a disease that resembles COPD. PM014 treatment significantly attenuated the increased accumulation of immune cells in bronchoalveolar lavage fluid (BALF) compared to control mice. In addition, the TNF-alpha and IL-6 levels in BALF were decreased in the PM014 mice. Furthermore, histological analysis demonstrated that PM014 attenuated the hazardous effects of lung inflammation. These data suggest that PM014 exerts beneficial effects against forms of COPD such as lung inflammation. PMID- 22778778 TI - Bioassay-Guided Isolation of Neuroprotective Compounds from Uncaria rhynchophylla against Beta-Amyloid-Induced Neurotoxicity. AB - Uncaria rhynchophylla is a component herb of many Chinese herbal formulae for the treatment of neurodegenerative diseases. Previous study in our laboratory has demonstrated that an ethanol extract of Uncaria rhynchophylla ameliorated cognitive deficits in a mouse model of Alzheimer's disease induced by D galactose. However, the active ingredients of Uncaria rhynchophylla responsible for the anti-Alzheimer's disease activity have not been identified. This study aims to identify the active ingredients of Uncaria rhynchophylla by a bioassay guided fractionation approach and explore the acting mechanism of these active ingredients by using a well-established cellular model of Alzheimer's disease, beta-amyloid- (Abeta-) induced neurotoxicity in PC12 cells. The results showed that six alkaloids, namely, corynoxine, corynoxine B, corynoxeine, isorhynchophylline, isocorynoxeine, and rhynchophylline were isolated from the extract of Uncaria rhynchophylla. Among them, rhynchophylline and isorhynchophylline significantly decreased Abeta-induced cell death, intracellular calcium overloading, and tau protein hyperphosphorylation in PC12 cells. These results suggest that rhynchophylline and isorhynchophylline are the major active ingredients responsible for the protective action of Uncaria rhynchophylla against Abeta-induced neuronal toxicity, and their neuroprotective effect may be mediated, at least in part, by inhibiting intracellular calcium overloading and tau protein hyperphosphorylation. PMID- 22778779 TI - The Hypouricemic Effect of Balanophora laxiflora Extracts and Derived Phytochemicals in Hyperuricemic Mice. AB - The objective of this study is to evaluate the lowering of uric acid using Balanophora laxiflora extracts and derived phytochemicals on potassium-oxonate (PO-) induced hyperuricemia in mice. The results revealed that ethyl acetate (EtOAc) fraction of B. laxiflora extracts exhibited strong xanthine-oxidase-(XOD ) inhibitory activity. In addition, among the 10 subfractions (EA1-10) derived from EtOAc fraction, subfraction 8 (EA8) exhibited the best XOD-inhibitory activity. Four specific phytochemicals, 1-O-(E)-caffeoyl-beta-D-glucopyranose (1), 1-O-(E)-p-coumaroyl-beta-D-glucopyranose (2), 1,3-di-O-galloyl-4,6-(S) hexahydroxydiphenoyl-beta-D-glucopyranose (3), and 1-O-(E)-caffeoyl-4,6-(S) hexahydroxydiphenoyl-beta-D-glucopyranose (4), were further isolated and identified from this subfraction. Compounds 3 and 4 exhibited the strongest XOD inhibitory activity compared with other compounds, and both hydrolyzable tannins were determined to be noncompetitive inhibitors according to the Lineweaver-Burk plot. On the other hand, the in vivo hypouricemic effect in hyperuricemic mice was consistent with XOD-inhibitory activity, indicating that B. laxiflora extracts and derived phytochemicals could be potential candidates as new hypouricemic agents. PMID- 22778780 TI - Pseudolaric Acid B induces caspase-dependent and caspase-independent apoptosis in u87 glioblastoma cells. AB - Pseudolaric acid B (PLAB) is one of the major bioactive components of Pseudolarix kaempferi. It has been reported to exhibit inhibitory effect on cell proliferation in several types of cancer cells. However, there is no report elucidating its effect on glioma cells and organ toxicity in vivo. In the present study, we found that PLAB inhibited growth of U87 glioblastoma cells in a dose dependent manner with IC(50)~10 MUM. Flow cytometry analysis showed that apoptotic cell death mediated by PLAB was accompanied with cell cycle arrest at G2/M phase. Using Western blot, we found that PLAB induced G2/M phase arrest by inhibiting tubulin polymerization in U87 cells. Apoptotic cell death was only partially inhibited by pancaspase inhibitor, z-VAD-fmk, which suggested that PLAB induced apoptosis in U87 cells is partially caspase-independent. Further mechanistic study demonstrated that PLAB induced caspase-dependent apoptosis via upregulation of p53, increased level of proapoptotic protein Bax, decreased level of antiapoptotic protein Bcl-2, release of cytochrome c from mitochondria, activation of caspase-3 and proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-independent apoptosis through apoptosis inducing factor (AIF). Furthermore, in vivo toxicity study demonstrated that PLAB did not induce significant structural and biochemical changes in mouse liver and kidneys at a dose of 25 mg/kg. Therefore, PLAB may become a potential lead compound for future development of antiglioma therapy. PMID- 22778781 TI - Application of metabolomics in traditional chinese medicine differentiation of deficiency and excess syndromes in patients with diabetes mellitus. AB - Metabolic profiling is widely used as a probe in diagnosing diseases. In this study, the metabolic profiling of urinary carbohydrates was investigated using gas chromatography/mass spectrometry (GC/MS) and multivariate statistical analysis. The kernel-based orthogonal projections to latent structures (K-OPLS) model were established and validated to distinguish between subjects with and without diabetes mellitus (DM). The model was combined with subwindow permutation analysis (SPA) in order to extract novel biomarker information. Furthermore, the K-OPLS model visually represented the alterations in urinary carbohydrate profiles of excess and deficiency syndromes in patients with diabetes. The combination of GC/MS and K-OPLS/SPA analysis allowed the urinary carbohydrate metabolic characterization of DM patients with different traditional Chinese medicine (TCM) syndromes, including biomarkers different from non-DM patients. The method presented in this study might be a complement or an alternative to TCM syndrome research. PMID- 22778782 TI - Caffeic Acid Phenylethyl Amide Protects against the Metabolic Consequences in Diabetes Mellitus Induced by Diet and Streptozocin. AB - Caffeic acid phenyl ester is distributed wildly in nature and has antidiabetic and cardiovascular protective effects. However, rapid decomposition by esterase leads to its low bioavailability in vivo. In this study, chronic metabolic and cardiovascular effects of oral caffeic acid phenylethyl amide, whose structure is similar to caffeic acid phenyl ester and resveratrol, were investigated in ICR mice. We found that caffeic acid phenylethyl amide protected against diet or streptozocin-induced metabolic changes increased coronary flow and decreased infarct size after global ischemia-reperfusion in Langendorff perfused heart. Further study indicated that at least two pathways might be involved in such beneficial effects: the induction of the antioxidant protein MnSOD and the decrease of the proinflammatory cytokine TNFalpha and NFkappaB in the liver. However, the detailed mechanisms of caffeic acid phenylethyl amide need further studies. In summary, this study demonstrated the protective potential of chronic treatment of caffeic acid phenylethyl amide against the metabolic consequences in diabetes mellitus. PMID- 22778783 TI - The HYP-RT hypoxic tumour radiotherapy algorithm and accelerated repopulation dose per fraction study. AB - The HYP-RT model simulates hypoxic tumour growth for head and neck cancer as well as radiotherapy and the effects of accelerated repopulation and reoxygenation. This report outlines algorithm design, parameterisation and the impact of accelerated repopulation on the increase in dose/fraction needed to control the extra cell propagation during accelerated repopulation. Cell kill probabilities are based on Linear Quadratic theory, with oxygenation levels and proliferative capacity influencing cell death. Hypoxia is modelled through oxygen level allocation based on pO(2) histograms. Accelerated repopulation is modelled by increasing the stem cell symmetrical division probability, while the process of reoxygenation utilises randomised pO(2) increments to the cell population after each treatment fraction. Propagation of 10(8) tumour cells requires 5-30 minutes. Controlling the extra cell growth induced by accelerated repopulation requires a dose/fraction increase of 0.5-1.0 Gy, in agreement with published reports. The average reoxygenation pO(2) increment of 3 mmHg per fraction results in full tumour reoxygenation after shrinkage to approximately 1 mm. HYP-RT is a computationally efficient model simulating tumour growth and radiotherapy, incorporating accelerated repopulation and reoxygenation. It may be used to explore cell kill outcomes during radiotherapy while varying key radiobiological and tumour specific parameters, such as the degree of hypoxia. PMID- 22778784 TI - The effect of neural noise on spike time precision in a detailed CA3 neuron model. AB - Experimental and computational studies emphasize the role of the millisecond precision of neuronal spike times as an important coding mechanism for transmitting and representing information in the central nervous system. We investigate the spike time precision of a multicompartmental pyramidal neuron model of the CA3 region of the hippocampus under the influence of various sources of neuronal noise. We describe differences in the contribution to noise originating from voltage-gated ion channels, synaptic vesicle release, and vesicle quantal size. We analyze the effect of interspike intervals and the voltage course preceding the firing of spikes on the spike-timing jitter. The main finding of this study is the ranking of different noise sources according to their contribution to spike time precision. The most influential is synaptic vesicle release noise, causing the spike jitter to vary from 1 ms to 7 ms of a mean value 2.5 ms. Of second importance was the noise incurred by vesicle quantal size variation causing the spike time jitter to vary from 0.03 ms to 0.6 ms. Least influential was the voltage-gated channel noise generating spike jitter from 0.02 ms to 0.15 ms. PMID- 22778785 TI - Cytohistological correlation of early changes in spontaneously infarcted fibroadenoma-a rare case report. AB - Fibroadenoma is the most commonly diagnosed benign tumour in adolescents and young women but spontaneous infarction in fibroadenoma is rarely seen. We report here a case of spontaneously infracted fibroadenoma in a 20 year old unmarried female without history of trauma or previous fine needle aspiration. It is important to recognize this entity because microscopic findings in an infarct are influenced by the duration of the infarct and on cytology it mimics mastitis, duct ectasia and even carcinoma. PMID- 22778786 TI - HPV-DNA testing for cervical cancer precursors: from evidence to clinical practice. AB - The large amount of literature published over the last two decades on human papillomavirus (HPV)-DNA testing has definitely demonstrated the association between high-risk viral genotypes (hrHPV) and cervical cancer. Moreover, hrHPV DNA testing has shown excellent performance in several clinical applications, from screening settings to the follow-up of treated patients, compared to conventional cytology or colposcopy options. On the other hand, when a huge number of reports are published on the same subject in a relatively short period of time, with many variations in settings, study designs and applications, the result is often confusion and decreased comprehension by readers. In daily office practice, several different situations (in symptomatic or asymptomatic women) can be positively managed by the correct use of hrHPV-DNA testing. Validated hrHPV DNA testing and, specifically, the HC2(r) assay, due to its excellent sensitivity and negative predictive value together with optimal reproducibility, currently represent a powerful tool in the clinician's hands to optimally manage several situations related to HPV infection and the potential development of cervical cancer. PMID- 22778787 TI - Irritable bowel syndrome and ischemic colitis: evidence supporting the increased use of alosetron. PMID- 22778788 TI - Overutilization of proton-pump inhibitors: what the clinician needs to know. AB - Proton-pump inhibitors (PPIs) remain the leading evidence-based therapy for upper gastrointestinal disorders, including gastroesophageal reflux disease, dyspepsia, and peptic ulcer disease. The effectiveness of PPIs has led to overutilization in multiple treatment arenas, exposing patients to an increasing number of potential risks. The overutilization of PPIs in ambulatory care settings is often a result of failure to re-evaluate the need for continuation of therapy, or insufficient use of on-demand and step-down therapy. PPI overutilization in the inpatient setting is often a result of inappropriate stress ulcer prophylaxis (SUP) in nonintensive care unit patients, and failure to discontinue SUP prior to hospital discharge. Potential consequences of prolonged PPI therapy include hypergastrinemia, enterochromaffin-like cell hyperplasia, and parietal cell hypertrophy, leading to rebound acid hypersecretion. PPIs have been linked via retrospective studies to increased risk of enteric infections including Clostridium difficile-associated diarrhea, community-acquired pneumonia, bone fracture, nutritional deficiencies, and interference with metabolism of antiplatelet agents. Reducing inappropriate prescribing of PPIs in the inpatient and outpatient settings can minimize potential for adverse events, and foster controllable cost expenditure. PMID- 22778789 TI - Chronic constipation: new diagnostic and treatment approaches. AB - Chronic constipation is a highly prevalent disorder that affects approximately 15% of the US population. Chronic constipation refers to patients who have had symptoms for more than 6 months. In clinical practice, chronic constipation is often used interchangeably with the term functional constipation. This is best defined using the Rome III criteria, which involves an evaluation of stool frequency in addition to symptoms of straining, feelings of incomplete evacuation, and the need to use manual maneuvers to assist with stool evacuation. Symptoms can be burdensome, leading to a reduction in patients' quality of life. As a national healthcare issue, chronic constipation is also important because it imposes a significant economic impact on the healthcare system. A number of treatment options are currently available, both over-the-counter and by prescription, although not all patients respond to these therapies. This review will focus on new medical treatment options for the management of chronic constipation, and the safety and efficacy of these agents will be reviewed. In addition, the efficacy of new diagnostic tests to evaluate colonic motility and anorectal function are described. PMID- 22778790 TI - Evaluation of regional and whole gut motility using the wireless motility capsule: relevance in clinical practice. AB - The wireless motility capsule (WMC) is an ambulatory noninvasive and nonradioactive diagnostic sensor that continuously samples intraluminal pH, temperature, and pressure as it moves through the gastrointestinal (GI) tract. This review summarizes the data obtained in clinical trials with the WMC and discusses its role in clinical practice. The United States Food and Drug Administration has approved the SmartPill GI monitoring system for the evaluation of gastric emptying time in patients with suspected gastroparesis, the evaluation of colonic transit time in patients with suspected chronic constipation, and for the characterization of pressure profiles from the antrum and duodenum. Clinical studies have shown that WMC-measured GI transit times can distinguish patients with motility abnormalities similarly to conventional testing. However, the WMC offers the advantage of providing a full GI-tract profile, enabling the detection of multiregional GI transit abnormalities in patients with suspected upper or lower GI dysmotility. The WMC also characterizes pressure profiles of the GI tract and impaired pressure profile limits are reported for the antrum and duodenum. In comparison with manometry, interpretations of pressure measurements obtained by the WMC are limited by an inability to detect a peristaltic pressure wave front, and further investigation is required to develop clinical applications. Clinical studies with the WMC indicated that it should be considered for the evaluation of regional and whole gut transit time in patients with suspected upper or lower dysmotility, particularly if there are concerns about multiregional dysmotility. PMID- 22778791 TI - Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and nonallergic food intolerance: FODMAPs or food chemicals? AB - Food intolerance in irritable bowel syndrome (IBS) is increasingly being recognized, with patients convinced that diet plays a role in symptom induction. Evidence is building to implicate fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) in the onset of abdominal pain, bloating, wind and altered bowel habit through their fermentation and osmotic effects. Hypersensitivity to normal levels of luminal distension is known to occur in patients with IBS, with consideration of food chemical intolerance likely to answer many questions about this physiological process. This paper summarizes the evidence and application of the most common approaches to managing food intolerance in IBS: the low-FODMAP diet, the elimination diet for food chemical sensitivity and others including possible noncoeliac gluten intolerance. PMID- 22778792 TI - Decision aids for patients. AB - BACKGROUND: Patients want to be more involved in medical decision-making. To this end, some decision aids are now available. METHODS: We present an overview of this subject, in which we explain the terms "shared decision-making", "decision aid", and "evidence-based patient information" and survey information on the available decision aids in German and other languages on the basis of a literature search in MEDLINE, EMBASE and PsycInfo and a current Cochrane Review. We also searched the Internet for providers of decision aids in Germany. RESULTS: Decision aids exist in the form of brochures, decision tables, videos, and computer programs; they address various topics in the prevention, diagnosis, and treatment of disease. They typically contain information on the advantages and disadvantages of the available options, as well as guidance for personal decision making. They can be used alone or as a part of structured counseling or patient education. Minimal quality standards include an adequate evidence base, completeness, absence of bias, and intelligibility. Our search revealed 12 randomized controlled trials (RCTs) of decision aids in German and 106 RCTs of decision aids in other languages. These trials studied the outcome of the use of decision aids not just with respect to clinical developments, but also with respect to patient knowledge, adherence to treatment regimens, satisfaction, involvement in decision-making, autonomy preference, and decisional conflicts. CONCLUSION: Only a small fraction of the available decision aids were systematically developed and have been subjected to systematic evaluation. Patients are still not receiving the help in decision-making to which medical ethics entitles them. Structures need to be put in place for the sustainable development, evaluation and implementation of high-quality decision aids. PMID- 22778794 TI - Correspondence (letter to the editor): Woolly Explanation. PMID- 22778793 TI - Chronic intestinal failure in children. AB - BACKGROUND: Chronic intestinal failure (CIF) in childhood is caused by congenital malformations and inflammatory diseases of the gut. Its reported prevalence is 13.7 per million population. Long-term home parenteral nutrition has dramatically improved the life expectancy and quality of life of children with CIF. The affected children are now treated with parenteral nutrition at home as soon as their medical state and family circumstances allow. METHODS: The authors present data from a patient registry and review publications retrieved by a selective literature search. RESULTS AND CONCLUSION: Children with CIF can now be expected to survive beyond adolescence, at the very least, and enjoy good quality of life. This goal can only be achieved if nutritional therapy is carried out safely and the affected children's development is closely monitored by an interdisciplinary team that consists of primary care physicians/family doctors, neonatologists, pediatric gastroenterologists, and pediatric surgeons. Moreover, the prevention, early detection, and appropriate treatment of complications such as infection, liver disease, renal dysfunction, and disturbances of bone metabolism is of vital importance. The patients' families must be supported by specially qualified ambulatory nurses and social workers. Treatment with parenteral, enteral, and oral nutrition and surgery enables most infants with CIF to meet all their nutritional needs orally by the time they start going to school. For children who suffer from intractable complications, intestinal transplantation provides a real and increasing chance of survival. PMID- 22778796 TI - Correspondence (letter to the editor): Medical Rehabilitation. PMID- 22778798 TI - Preschool Children with and without Developmental Delay: Risk, Parenting, and Child Demandingess. AB - Although past literature has established relations between early child risk factors, negative parenting, and problematic child behavior, the nature of these interrelations and pathways of influence over time remains largely unknown, especially in children with developmental delays or disabilities. In the current study data were drawn from the longitudinal Collaborative Family Study and included a sample of 260 families with preschool children with and without developmental delays. Child-related risk was assessed at child age 36 months, maternal intrusiveness and negative affect at 48 months, and child demandingness at 60 months. Results indicated significant relations between early risk, negative parenting, and subsequent child demandingness. Sickliness as an infant was the most salient predictive risk factor of later child demandingness. Developmental delay was the most significant predictor of subsequent negative parenting. Results are discussed as being more indicative of additive rather than mediational processes given that early child risk and negative maternal parenting both contributed uniquely to the subsequent development of child demandingness. PMID- 22778799 TI - Reactive oxygen species formation and apoptosis in human peripheral blood mononuclear cell induced by 900 MHz mobile phone radiation. AB - We demonstrate that reactive oxygen species (ROS) plays an important role in the process of apoptosis in human peripheral blood mononuclear cell (PBMC) which is induced by the radiation of 900 MHz radiofrequency electromagnetic field (RFEMF) at a specific absorption rate (SAR) of ~0.4 W/kg when the exposure lasts longer than two hours. The apoptosis is induced through the mitochondrial pathway and mediated by activating ROS and caspase-3, and decreasing the mitochondrial potential. The activation of ROS is triggered by the conformation disturbance of lipids, protein, and DNA induced by the exposure of GSM RFEMF. Although human PBMC was found to have a self-protection mechanism of releasing carotenoid in response to oxidative stress to lessen the further increase of ROS, the imbalance between the antioxidant defenses and ROS formation still results in an increase of cell death with the exposure time and can cause about 37% human PBMC death in eight hours. PMID- 22778800 TI - Rational Drug Design Leading to the Identification of a Potent 5-HT(2C) Agonist Lacking 5-HT(2B) Activity. AB - The 5-HT(2C) receptor is an attractive drug target in the quest for new therapeutics to treat a variety of human disorders. We have previously undertaken a structural optimization campaign that has led to some potent and moderately selective 5-HT(2C) receptor agonists. After expanding our structure-function library, we were able to combine our datasets so as to allow the design of compounds of improved selectivity and potency. We disclose herein the structural optimization of our previously reported 5-HT(2B)/5-HT(2C) agonists, which has led to the identification of a highly selective 5-HT(2C) agonist, (+)-trans-[2-(2 cyclopropylmethoxyphenyl)cyclopropyl]methylamine hydrochloride, with an EC(50) of 55 nM and no detectable agonism at the 5-HT(2B) receptor. PMID- 22778803 TI - Amyloid beta-protein aggregation produces highly reproducible kinetic data and occurs by a two-phase process. AB - Protein aggregation can lead to major disturbances of cellular processes and is associated with several diseases. We report kinetic and equilibrium data by ThT fluorescence and enzyme-linked immunosorbent assay of sufficient quality and reproducibility to form a basis for mechanistic understanding of amyloid beta peptide (Abeta) fibril formation. Starting from monomeric peptide in a pure buffer system without cosolvents, we find that the kinetics of Abeta aggregation vary strongly with peptide concentration in a highly predictable manner. The free Abeta concentration in equilibrium with fibrils was found to vary with total peptide concentration in a manner expected for a two-phase system. The free versus total Abeta concentration was linear up to ca. 0.2 MUM, after which free Abeta decreased with total Abeta toward an asymptotic value. Our results imply that Abeta fibril formation arises from a sequence of events in a highly predictable manner. PMID- 22778802 TI - Intercellular glutamate signaling in the nervous system and beyond. AB - Most intercellular glutamate signaling in the nervous system occurs at synapses. Some intercellular glutamate signaling occurs outside synapses, however, and even outside the nervous system where high ambient extracellular glutamate might be expected to preclude the effectiveness of glutamate as an intercellular signal. Here, I briefly review the types of intercellular glutamate signaling in the nervous system and beyond, with emphasis on the diversity of signaling mechanisms and fundamental unanswered questions. PMID- 22778804 TI - Synthesis, structure-activity relationship, and pharmacological profile of analogs of the ASIC-3 inhibitor A-317567. AB - The synthesis, structure-activity relationship (SAR), and pharmacological evaluation of analogs of the acid-sensing ion channel (ASIC) inhibitor A-317567 are reported. It was found that the compound with an acetylenic linkage was the most potent ASIC-3 channel blocker. This compound reversed mechanical hypersensitivity in the rat iodoacetate model of osteoarthritis pain, although sedation was noted. Sedation was also observed in ASIC-3 knockout mice, questioning whether sedation and antinociception are mediated via a non-ASIC-3 specific mechanism. PMID- 22778806 TI - Horner's Syndrome and Neuroblastoma: our family's odyssey with disorders of the sympathetic nervous system. PMID- 22778805 TI - Engineering a GPCR-ligand pair that simulates the activation of D(2L) by Dopamine. AB - In the past decade, engineered G-protein-coupled receptors activated solely by synthetic ligands (RASSLs) have been implemented as a new means to study neurotransmission, which is controlled by G-protein-coupled receptors in vitro and in vivo. In this study, we report an engineered dopamine receptor D(2L) F390(6.52)W, which is the first identified RASSL for the dopamine receptor family. The mutant receptor is characterized by a disrupted ligand binding and complete loss of efficacy for the endogenous ligand, dopamine, which is putatively due to a sterically induced perturbation of H-bonding with conserved serine residues in TM5. Based on this model, we rationally developed an aminoindane-derived set of agonists. Because these agonists forgo analogous H bonding functionalities, their binding energy does not depend on the respective interactions. Binding affinity and potency were optimized by ligand modifications bearing molecular appendages that obviously interact with a secondary recognition site provided by four hydrophobic residues in TM2 and TM3. Thus, the ferrocenyl carboxamide 5b (FAUC 185) was identified as a synthetic agonist that is able to stimulate the mutant receptor in a manner similar to that by which endogenous dopamine activates the D(2L) wild-type receptor. The engineered dopamine receptor D(2L) F390(6.52)W in combination with FAUC 185 (5b) provides a new tool to probe GPCR functions selectively in specific cell populations in vitro and in vivo. PMID- 22778808 TI - ACS chemical neuroscience molecule spotlight on Lorcaserin. AB - Lorcaserin (APD-356) is the first in a new class of selective serotonin 5 hydroxytryptamine(2C) (5-HT(2C)) receptor agonists. On December 22, 2009, the compound's developer (Arena Pharmaceuticals) submitted an NDA to the FDA for approval for weight management. PMID- 22778807 TI - Effects of peptides derived from terminal modifications of the abeta central hydrophobic core on abeta fibrillization. AB - Considerable research effort has focused on the discovery of mitigators that block the toxicity of the beta-amyloid peptide (Abeta) by targeting a specific step involved in Abeta fibrillogenesis and subsequent aggregation. Given that aggregation intermediates are hypothesized to be responsible for Abeta toxicity, such compounds could likely prevent or mitigate aggregation, or alternatively cause further association of toxic oligomers into larger nontoxic aggregates. Herein we investigate the effect of modifications of the KLVFF hydrophobic core of Abeta by replacing N- and C-terminal groups with various polar moieties. Several of these terminal modifications were found to disrupt the formation of amyloid fibrils and in some cases induced the disassembly of preformed fibrils. Significantly, mitigators that incorporate MiniPEG polar groups were found to be effective against Abeta(1-40) fibrilligonesis. Previously, we have shown that mitigators incorporating alpha,alpha-disubstituted amino acids (alphaalphaAAs) were effective in disrupting fibril formation as well as inducing fibril disassembly. In this work, we further disclose that the number of polar residues (six) and alphaalphaAAs (three) in the original mitigator can be reduced without dramatically changing the ability to disrupt Abeta(1-40) fibrillization in vitro. PMID- 22778809 TI - Near-infrared fluorescence imaging of apoptotic neuronal cell death in a live animal model of prion disease. AB - Apoptotic cell death via activation of the caspase family of cysteine proteases is a common feature of many neurodegenerative diseases including Creutzfeldt Jakob disease. Molecular imaging of cysteine protease activities at the preclinical stage may provide valuable mechanistic information about pathophysiological pathways involved in disease evolution and in response to therapy. In this study, we report synthesis and characterization of a near infrared (NIR) fluorescent contrast agent capable of noninvasively imaging neuronal apoptosis in vivo, by conjugating a NIR cyanine dye to Val-Ala-Asp fluoromethylketone (VAD-fmk), a general inhibitor of active caspases. Following intravenous administration of the NIR-VAD-fmk contrast agent, in vivo fluorescence reflectance imaging identified significantly higher levels of active caspases in the brain of mice with advanced but preclinical prion disease, when compared with healthy controls. The contrast agent and related analogues will enable the longitudinal study of disease progression and therapy in animal models of many neurodegenerative conditions. PMID- 22778810 TI - Selective acetylcholinesterase inhibitor activated by acetylcholinesterase releases an active chelator with neurorescuing and anti-amyloid activities. AB - The finding that acetylcholinesterase (AChE) colocalizes with beta-amyloid (Abeta) and promotes and accelerates Abeta aggregation has renewed an intense interest in developing new multifunctional AChE inhibitors as potential disease modifying drugs for Alzheimer's therapy. To this end, we have developed a new class of selective AChE inhibitors with site-activated chelating activity. The identified lead, HLA20A, exhibits little affinity for metal (Fe, Cu, and Zn) ions but can be activated following inhibition of AChE to liberate an active chelator, HLA20. HLA20 has been shown to possess neuroprotective and neurorescuing activities in vitro and in vivo with the ability to lower amyloid precursor holoprotein (APP) expression and Abeta generation and inhibit Abeta aggregation induced by metal (Fe, Cu, and Zn) ion. HLA20A inhibited AChE in a time and concentration dependent manner with an HLA20A-AChE complex constant (K(i)) of 9.66 * 10(-6) M, a carbamylation rate (k(+2)) of 0.14 min(-1), and a second-order rate (k(i)) of 1.45 * 10 (4) M(-1) min(-1), comparable to those of rivastigmine. HLA20A showed little iron-binding capacity and activity against iron-induced lipid peroxidation (LPO) at concentrations of 1-50 MUM, while HLA20 exhibited high potency in iron-binding and in inhibiting iron-induced LPO. At a concentration of 10 MUM, HLA20A showed some activity against monoamine oxidase (MAO)-A and -B when tested in rat brain homogenates. Defined restrictively by Lipinski's rules, both HLA20A and HLA20 satisfied drug-like criteria and possible oral and brain permeability, but HLA20A was more lipophilic and considerably less toxic in human SHSY5Y neuroblastoma cells at high concentrations (25 or 50 MUM). Together our data suggest that HLA20A may represent a promising lead for further development for Alzheimer's disease therapy. PMID- 22778811 TI - Monoclonal antibody against the turn of the 42-residue amyloid beta-protein at positions 22 and 23. AB - Aggregation of the 42-mer amyloid beta-protein (Abeta42) plays a critical role in the pathogenesis of Alzheimer's disease (AD). We have proposed a toxic conformer with a turn at positions 22 and 23, as well as a nontoxic conformer with a turn at positions 25 and 26, in Abeta42 aggregates from systematic proline scanning and solid-state NMR studies. Although recent clinical trials of immunization targeting Abeta42 aggregates have proved useful, some adverse effects were reported. One of the reasons was hypothesized to be excessive immunoreactions derived from the unintended removal of nontoxic Abeta42, which plays an important role in the physiological function. To develop a monoclonal antibody for toxic Abeta42, E22P-Abeta10-35, a minimum moiety for neurotoxicity containing the turn at positions 22 and 23, was used for the generation of antibodies, following the selection of clones using Abeta42 mutants of E22P (turn-inducing) and E22V (turn preventing). The obtained clone (11A1) showed a high binding affinity (K(D) = 10.3 nM) for Abeta42 using surface plasmon resonance. 11A1 also inhibited the neurotoxicity of Abeta42 in PC12 cells. Immunohistochemical studies showed that not only extracellular but intracellular amyloid was stained in human AD brains. In Western blotting analyses using human brains, low-molecular weight-oligomers rather than the monomer of Abeta were readily recognized by 11A1. These results imply that 11A1 could detect toxic Abeta42 oligomers with the turn at positions 22 and 23 and that 11A1 could be applicable for the therapeutic targeting of toxic Abeta42 in AD. PMID- 22778814 TI - ACS chemical neuroscience molecule spotlight on Valdoxen. AB - A new and novel non-SSRI potential treatment option for major depressive disorders is Valdoxen (agomelatine) which is currently in phase III clinical studies. Valdoxen is a norepinephrine disinhibitor (NNDI) and is also an antagonist of the 5-HT(2C) receptor. PMID- 22778812 TI - Exploring the Backbone of Enkephalins To Adjust Their Pharmacological Profile for the delta-Opioid Receptor. AB - The role of each of the four amide bonds in Leu(5)-enkephalin was investigated by systematically and sequentially replacing each with its corresponding trans alkene. Six Leu(5)-enkephalin analogs based on six dipeptide surrogates and two Met(5)-enkephalin analogs were synthesized and thoroughly tested using a delta opioid receptor internalization assay, an ERK1/2 activation assay, and a competition binding assay to evaluate their biological properties. We observed that an E-alkene can efficiently replace the first amide bond of Leu(5)- and Met(5)-enkephalin without significantly affecting biological activity. By contrast, the second amide bond was found to be highly sensitive to the same modification, suggesting that it is involved in biologically essential intra- or intermolecular interactions. Finally, we observed that the affinity and activity of analogs containing an E-alkene at either the third or fourth position were partially reduced, indicating that these amide bonds are less important for these intra- or intermolecular interactions. Overall, our study demonstrates that the systematic and sequential replacement of amide bonds by E-alkene represents an efficient way to explore peptide backbones. PMID- 22778815 TI - Discovery of 1,5-disubstituted pyridones: a new class of positive allosteric modulators of the metabotropic glutamate 2 receptor. AB - A series of 1,5-disubstituted pyridones was identified as positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 2 (mGluR2) via high throughput screening (HTS). Subsequent SAR exploration led to the identification of several compounds with improved in vitro activity. Lead compound 8 was further profiled and found to attenuate the increase in PCP induced locomotor activity in mice. PMID- 22778816 TI - Identifying the binding site of novel methyllycaconitine (MLA) analogs at alpha4beta2 nicotinic acetylcholine receptors. AB - Neuronal nicotinic acetylcholine receptors (nAChR) are ligand gated ion channels that mediate fast synaptic transmission. Methyllycaconitine (MLA) is a selective and potent antagonist of the alpha7 nAChR, and its anthranilate ester side-chain is important for its activity. Here we report the influence of structure on nAChR inhibition for a series of novel MLA analogs, incorporating either an alcohol or anthranilate ester side-chain to an azabicyclic or azatricyclic core against rat alpha7, alpha4beta2, and alpha3beta4 nAChRs expressed in Xenopus oocytes. The analogs inhibited ACh (EC(50)) within an IC(50) range of 2.3-26.6 MUM. Most displayed noncompetitive antagonism, but the anthranilate ester analogs exerted competitive behavior at the alpha7 nAChR. At alpha4beta2 nAChRs, inhibition by the azabicyclic alcohol was voltage-dependent suggesting channel block. The channel-lining residues of alpha4 subunits were mutated to cysteine and the effect of azabicyclic alcohol was evaluated by competition with methanethiosulfonate ethylammonium (MTSEA) and a thiol-reactive probe in the open, closed, and desensitized states of alpha4beta2 nAChRs. The azabicyclic alcohol was found to compete with MTSEA between residues 6' and 13' in a state dependent manner, but the reactive probe only bonded with 13' in the open state. The data suggest that the 13' position is the dominant binding site. Ligand docking of the azabicyclic alcohol into a (alpha4)(3)(beta2)(2) homology model of the closed channel showed that the ligand can be accommodated at this location. Thus our data reveal distinct pharmacological differences between different nAChR subtypes and also identify a specific binding site for a noncompetitive channel blocker. PMID- 22778818 TI - Screening and beyond: new opportunities to advance neuroscience discovery. PMID- 22778817 TI - In vivo characterization of a smart MRI agent that displays an inverse response to calcium concentration. AB - Contrast agents for magnetic resonance imaging (MRI) that exhibit sensitivity toward specific ions or molecules represent a challenging but attractive direction of research. Here a Gd(3+) complex linked to an aminobis(methylenephosphonate) group for chelating Ca(2+) was synthesized and investigated. The longitudinal relaxivity (r(1)) of this complex decreases during the relaxometric titration with Ca(2+) from 5.76 to 3.57 mM(-1) s(-1) upon saturation. The r(1) is modulated by changes in the hydration number, which was confirmed by determination of the luminescence emission lifetimes of the analogous Eu(3+) complex. The initial in vivo characterization of this responsive contrast agent was performed by means of electrophysiology and MRI experiments. The investigated complex is fully biocompatible, having no observable effect on neuronal function after administration into the brain ventricles or parenchyma. Distribution studies demonstrated that the diffusivity of this agent is significantly lower compared with that of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). PMID- 22778819 TI - Lipid bilayer membrane-triggered presynaptic vesicle assembly. AB - The formation of functional synapses on artificial substrates is a very important step in the development of engineered in vitro neural networks. Spherical supported bilayer lipid membranes (SS-BLMs) are used here as a novel substrate to demonstrate presynaptic vesicle accumulation at an in vitro synaptic junction. Confocal fluorescence microscopy, cryo-transmission electron microscopy (cryo TEM), and fluorescence recovery after photobleaching (FRAP) experiments have been used to characterize the SS-BLMs. Conventional immunocytochemistry combined with confocal fluorescence microscopy was used to observe the formation of presynaptic vesicles at the neuron-SS-BLM contacts. These results indicate that lipid phases may play a role in the observed phenomenon, in addition to the chemical and electrostatic interactions between the neurons and SS-BLMs. The biocompatibility of lipid bilayers along with their membrane tunability makes the suggested approach a useful "toolkit" for many neuroengineering applications including artificial synapse formation and synaptogenesis in vivo. PMID- 22778820 TI - Involvement of protein kinase C in morphine tolerance at spinal levels of rats. AB - The present study was performed to investigate the possible role of protein kinase C (PKC) in morphine tolerance at spinal levels of rats. Intrathecal injection of 10 MUg of morphine induced increases in the hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation in rats. After intrathecal injections of 10 MUg of morphine (twice a day) lasted for 5 days, the antinociceptive effects induced by intrathecal injections of morphine decreased significantly in rats. Interestingly, we found that there were significant increases in the content of PKC in the dorsal horn of the spinal cord and the dorsal root ganglion, but not in the ventral horn of the spinal cord, in rats with morphine tolerance determined by Western blot, suggesting that PKC is involved in morphine tolerance at spinal levels of rats. Furthermore, our results demonstrated that chronic intrathecal injection of the PKC inhibitor significantly inhibited the development of morphine tolerance. Moreover, we found that the maintenance of morphine tolerance was blocked by intrathecal administration of a PKC inhibitor in rats, and the inhibitory effects of the PKC inhibitor on morphine tolerance lasted for more than two days. Taken together, the present study clearly showed that PKC is involved in morphine tolerance at the spinal level of rats and that intrathecal administration of a PKC inhibitor can block the development and maintenance of morphine tolerance. PMID- 22778821 TI - Improved neuronal tract tracing with stable biocytin-derived neuroimaging agents. AB - One of the main characteristics of brains is their profuse connectivity at different spatial scales. Understanding brain function evidently first requires a comprehensive description of neuronal anatomical connections. Not surprisingly a large number of histological markers were developed over the years that can be used for tracing mono- or polysynaptic connections. Biocytin is a classical neuroanatomical tracer commonly used to map brain connectivity. However, the endogenous degradation of the molecule by the action of biotinidase enzymes precludes its applicability in long-term experiments and limits the quality and completeness of the rendered connections. With the aim to improve the stability of this classical tracer, two novel biocytin-derived compounds were designed and synthesized. Here we present their greatly improved stability in biological tissue along with retained capacity to function as neuronal tracers. The experiments, 24 and 96 h postinjection, demonstrated that the newly synthesized molecules yielded more detailed and complete information about brain networks than that obtained with conventional biocytin. Preliminary results suggest that the reported molecular designs can be further diversified for use as multimodal tracers in combined MRI and optical or electron microscopy experiments. PMID- 22778822 TI - GlyT1 - Up from the Ashes. The importance of not condemning a mechanism based on a single chemotype. PMID- 22778825 TI - Establishment of a neurochemistry track under the new ACS guidelines. AB - The new guidelines put forth by the ACS for approved chemistry degrees provide departments with greater flexibility in designing their ACS majors. Under these guidelines, students receive foundational and in-depth chemistry training while allowing individual departments to use their creativity in developing a curriculum that best meets the needs of their students and plays to the strength of the department. The chemistry department at Concordia College has developed an ACS Neurochemistry track and shares how the program arose, some of the practical matters in developing it, and how it can be made to work well within a liberal arts college. PMID- 22778823 TI - Manganese accumulates within golgi apparatus in dopaminergic cells as revealed by synchrotron X-ray fluorescence nanoimaging. AB - Chronic exposure to manganese results in neurological symptoms referred to as manganism and is identified as a risk factor for Parkinson's disease. In vitro, manganese induces cell death in the dopaminergic cells, but the mechanisms of manganese cytotoxicity are still unexplained. In particular, the subcellular distribution of manganese and its interaction with other trace elements needed to be assessed. Applying synchrotron X-ray fluorescence nanoimaging, we found that manganese was located within the Golgi apparatus of PC12 dopaminergic cells at physiologic concentrations. At increasing concentrations, manganese accumulates within the Golgi apparatus until cytotoxic concentrations are reached resulting in a higher cytoplasmic content probably after the Golgi apparatus storage capacity is exceeded. Cell exposure to manganese and brefeldin A, a molecule known to specifically cause the collapse of the Golgi apparatus, results in the striking intracellular redistribution of manganese, which accumulates in the cytoplasm and the nucleus. These results indicate that the Golgi apparatus plays an important role in the cellular detoxification of manganese. In addition manganese exposure induces a decrease in total iron content, which could contribute to the overall neurotoxicity. PMID- 22778826 TI - ACS chemical neuroscience molecule spotlight on Saphris. AB - On August 14th, 2009, for the first time, the FDA has approved a psychotropic medication for two indications simultaneously. Saphris (asenapine) is a multitarget atypical antipsychotic medication approved to treat adults with schizophrenia and bipolar I disorder. PMID- 22778827 TI - Dual effect of amino modified polystyrene nanoparticles on amyloid beta protein fibrillation. AB - The fibrillation kinetics of the amyloid beta peptide is analyzed in presence of cationic polystyrene nanoparticles of different size. The results highlight the importance of the ratio between the peptide and particle concentration. Depending on the specific ratio, the kinetic effects vary from acceleration of the fibrillation process by reducing the lag phase at low particle surface area in solution to inhibition of the fibrillation process at high particle surface area. The kinetic behavior can be explained if we assume a balance between two different pathways: first fibrillation of free monomer in solution and second nucleation and fibrillation promoted at the particle surface. The overall rate of fibrillation will depend on the interplay between these two pathways, and the predominance of one mechanism over the other will be determined by the relative equilibrium and rate constants. PMID- 22778829 TI - Torn from the headlines: AstraZeneca fined for illegal marketing of SEROQUEL. PMID- 22778828 TI - Effects of Congo red on abeta(1-40) fibril formation process and morphology. AB - Alzheimer's disease (AD), an age-related neurodegenerative disorder, is the most common form of dementia, and the seventh-leading cause of death in the United States. Current treatments offer only symptomatic relief; thus, there is a great need for new treatments with disease-modifying potential. One pathological hallmark of AD is so-called senile plaques, mainly made up of beta-sheet-rich assemblies of 40- or 42-residue amyloid beta-peptides (Abeta). Hence, inhibition of Abeta aggregation is actively explored as an option to prevent or treat AD. Congo red (CR) has been widely used as a model antiamyloid agent to prevent Abeta aggregation. Herein, we report detailed morphological studies on the effect of CR as an antiamyloid agent, by circular dichroism spectroscopy, photo-induced cross linking reactions, and atomic force microscopy. We also demonstrate the effect of CR on a preaggregated sample of Abeta(1-40). Our result suggests that Abeta(1-40) follows a different path for aggregation in the presence of CR. PMID- 22778830 TI - ACS chemical neuroscience molecule spotlight on savella. AB - Savella (milnacipran), a selective serotonin and noradrenaline reuptake inhibitor, was approved by the FDA on January 14th, 2009, for the treatment of fibromyalgia. PMID- 22778831 TI - Overeating, obesity, and dopamine receptors. AB - New results in rats show that compulsive overfeeding can lead to deficits in the brain reward circuit. Interestingly, these deficits resemble those that result from drug addiction. PMID- 22778832 TI - Reduced 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-initiated oxidative DNA damage and neurodegeneration in prostaglandin H synthase-1 knockout mice. AB - The neurodegenerative potential of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and underlying mechanisms are under debate. Here, we show that MDMA is a substrate for CNS prostaglandin H synthase (PHS)-catalyzed bioactivation to a free radical intermediate that causes reactive oxygen species (ROS) formation and neurodegenerative oxidative DNA damage. In vitro PHS-1-catalyzed bioactivation of MDMA stereoselectively produced free radical intermediate formation and oxidative DNA damage that was blocked by the PHS inhibitor eicosatetraynoic acid. In vivo, MDMA stereoselectively caused gender-independent DNA oxidation and dopaminergic nerve terminal degeneration in several brain regions, dependent on regional PHS-1 levels. Conversely, MDMA-initiated striatal DNA oxidation, nerve terminal degeneration, and motor coordination deficits were reduced in PHS-1 +/- and -/- knockout mice in a gene dose-dependent fashion. These results confirm the neurodegenerative potential of MDMA and provide the first direct evidence for a novel molecular mechanism involving PHS-catalyzed formation of a neurotoxic MDMA free radical intermediate. PMID- 22778833 TI - Delivery of neuropeptides from the periphery to the brain: studies with enkephalin. AB - Many peptides with the potential of therapeutic action for brain disorders are not in clinical use because they are unable to cross the blood-brain barrier (BBB) following peripheral administration. We have developed two potential strategies for the delivery of peptides to the brain and demonstrated their feasibility with enkephalins. In the first approach, designated induced reversible lipophilization, Leu/Met Enkephalins were converted to 9 fluorenylmethoxycarbonyl (Fmoc) derived lipophilic prodrug analogues, which undergo slow, spontaneous hydrolysis under physiological conditions, generating the native agonists. In contrast to Enkephalin, Fmoc-Met-Enkephalin was found to facilitate an analgesic effect following intraperitoneal administration in mice. Fmoc-Leu-Enkephalin was not analgesic. In the second approach, Enkephalin was linked to BBB transport vectors through an Fmoc based linker spacer, forming conjugates that slowly release Enkephalin under physiological conditions. A pronounced antinociceptive response was thus obtained following intraperitoneal administration of either cationized-human serum albumin-Fmoc-Enkephalin or polyethylene glycol(5)-Fmoc-Enkephalin. Derivatives of Enkephalin covalently linked to the same BBB-transport vectors through a stable (nonreversible) chemical bond were not analgesic. In summary, we have demonstrated that lipophilicity can be conferred to hydrophilic peptides to a degree permitting the permeation of the BBB by passive diffusion, without the drawback of agonist inactivation, which is often caused by irreversible derivatization. Similarly, in the second strategy, the conjugation to BBB-permeable vectors overcomes the obstacle of peptide inactivation by releasing the active form in the central nervous system. PMID- 22778834 TI - The top prescription drugs of 2009 in the US: CNS therapeutics rank among highest grossing. PMID- 22778835 TI - ACS chemical neuroscience molecule spotlight on Fanapt. AB - The new mixed dopamaine D(2)/serotonin 5-HT(2A) antagonist, Fanapt (iloperidone), was approved by the FDA on May 6th, 2009 for the treatment of schizophrenia in adults. PMID- 22778836 TI - Defining desirable central nervous system drug space through the alignment of molecular properties, in vitro ADME, and safety attributes. AB - As part of our effort to increase survival of drug candidates and to move our medicinal chemistry design to higher probability space for success in the Neuroscience therapeutic area, we embarked on a detailed study of the property space for a collection of central nervous system (CNS) molecules. We carried out a thorough analysis of properties for 119 marketed CNS drugs and a set of 108 Pfizer CNS candidates. In particular, we focused on understanding the relationships between physicochemical properties, in vitro ADME (absorption, distribution, metabolism, and elimination) attributes, primary pharmacology binding efficiencies, and in vitro safety data for these two sets of compounds. This scholarship provides guidance for the design of CNS molecules in a property space with increased probability of success and may lead to the identification of druglike candidates with favorable safety profiles that can successfully test hypotheses in the clinic. PMID- 22778837 TI - Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties. AB - The interplay among commonly used physicochemical properties in drug design was examined and utilized to create a prospective design tool focused on the alignment of key druglike attributes. Using a set of six physicochemical parameters ((a) lipophilicity, calculated partition coefficient (ClogP); (b) calculated distribution coefficient at pH = 7.4 (ClogD); (c) molecular weight (MW); (d) topological polar surface area (TPSA); (e) number of hydrogen bond donors (HBD); (f) most basic center (pK(a))), a druglikeness central nervous system multiparameter optimization (CNS MPO) algorithm was built and applied to a set of marketed CNS drugs (N = 119) and Pfizer CNS candidates (N = 108), as well as to a large diversity set of Pfizer proprietary compounds (N = 11 303). The novel CNS MPO algorithm showed that 74% of marketed CNS drugs displayed a high CNS MPO score (MPO desirability score >= 4, using a scale of 0-6), in comparison to 60% of the Pfizer CNS candidates. This analysis suggests that this algorithm could potentially be used to identify compounds with a higher probability of successfully testing hypotheses in the clinic. In addition, a relationship between an increasing CNS MPO score and alignment of key in vitro attributes of drug discovery (favorable permeability, P-glycoprotein (P-gp) efflux, metabolic stability, and safety) was seen in the marketed CNS drug set, the Pfizer candidate set, and the Pfizer proprietary diversity set. The CNS MPO scoring function offers advantages over hard cutoffs or utilization of single parameters to optimize structure-activity relationships (SAR) by expanding medicinal chemistry design space through a holistic assessment approach. Based on six physicochemical properties commonly used by medicinal chemists, the CNS MPO function may be used prospectively at the design stage to accelerate the identification of compounds with increased probability of success. PMID- 22778839 TI - ACS chemical neuroscience molecule spotlight on Sabril. AB - Sabril (vigabatrin) oral solution was approved by the FDA on August 21st, 2009 for treatment of infantile spasms in children ages 1 month to 2 years and complex partial seizures in adults (tablets). PMID- 22778838 TI - Antipsychotic drugs activate the C. elegans akt pathway via the DAF-2 insulin/IGF 1 receptor. AB - The molecular modes of action of antipsychotic drugs are poorly understood beyond their effects at the dopamine D2 receptor. Previous studies have placed Akt signaling downstream of D2 dopamine receptors, and recent data have suggested an association between psychotic illnesses and defective Akt signaling. To characterize the effect of antipsychotic drugs on the Akt pathway, we used the model organism C. elegans, a simple system where the Akt/forkhead box O transcription factor (FOXO) pathway has been well characterized. All major classes of antipsychotic drugs increased signaling through the insulin/Akt/FOXO pathway, whereas four other drugs that are known to affect the central nervous system did not. The antipsychotic drugs inhibited dauer formation, dauer recovery, and shortened lifespan, three biological processes affected by Akt signaling. Genetic analysis showed that AKT-1 and the insulin and insulin-like growth factor receptor, DAF-2, were required for the antipsychotic drugs to increase signaling. Serotonin synthesis was partially involved, whereas the mitogen activated protein kinase (MAPK), SEK-1 is a MAP kinase kinase (MAPKK), and calcineurin were not involved. This is the first example of a common but specific molecular effect produced by all presently known antipsychotic drugs in any biological system. Because untreated schizophrenics have been reported to have low levels of Akt signaling, increased Akt signaling might contribute to the therapeutic actions of antipsychotic drugs. PMID- 22778840 TI - Akt-dependent and isoform-specific regulation of dopamine transporter cell surface expression. AB - Dopamine (DA) is a neurotransmitter implicated in multiple functions, including movement, cognition, motivation, and reward. The DA transporter (DAT) is responsible for clearing extracellular DA, thereby terminating DA neurotransmission. Previously, it has been shown that insulin signaling through protein kinase B/Akt regulates DAT function by fine-tuning DAT cell surface expression. Importantly, specific Akt isoforms (e.g., Akt1, Akt2) serve distinct physiological functions. Here, we demonstrate using isoform-specific Akt inhibitors that basal activity of Akt2, rather than Akt1, regulates DAT cell surface expression. Since Akt2 activation is mediated by insulin, these data further implicate insulin signaling as an important modulator of DAT function and dopaminergic tone. PMID- 22778841 TI - Native serotonin membrane receptors recognize 5-hydroxytryptophan-functionalized substrates: enabling small-molecule recognition. AB - Recognition of small diffusible molecules by large biomolecules is ubiquitous in biology. To investigate these interactions, it is important to be able to immobilize small ligands on substrates; however, preserving recognition by biomolecule-binding partners under these circumstances is challenging. We have developed methods to modify substrates with serotonin, a small-molecule neurotransmitter important in brain function and psychiatric disorders. To mimic soluble serotonin, we attached its amino acid precursor, 5-hydroxytryptophan, via the ancillary carboxyl group to oligo(ethylene glycol)-terminated alkanethiols self-assembled on gold. Anti-5-hydroxytryptophan antibodies recognize these substrates, demonstrating bioavailability. Interestingly, 5-hydroxytryptophan functionalized surfaces capture membrane-associated serotonin receptors enantiospecifically. By contrast, surfaces functionalized with serotonin itself fail to bind serotonin receptors. We infer that recognition by biomolecules evolved to distinguish small-molecule ligands in solution requires tethering of the latter via ectopic moieties. Membrane proteins, which are notoriously difficult to isolate, or other binding partners can be captured for identification, mapping, expression, and other purposes using this generalizable approach. PMID- 22778844 TI - (S)-(+)-mecamylamine (TC-5214): a neuronal nicotinic receptor modulator enters phase III trials as an adjunct treatment for Major Depressive Disorder (MDD). PMID- 22778842 TI - In vivo evaluation of limiting brain penetration of probes for alpha(2C) adrenoceptor using small-animal positron emission tomography. AB - To evaluate in vivo brain penetration of alpha(2C)-adrenoceptor (alpha(2C)-AR) antagonists as a therapeutic agent, we synthesized two new (11)C-labeled selective alpha(2C)-AR antagonists 4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin 2-yl)methyl-2-aryl-7-methoxybenzofuran ([(11)C]MBF) and acridin-9-yl-[4-(4 methylpiperazin-1-yl)phenyl]amine ([(11)C]JP-1302) as alpha(2C)-AR-selective positron emission tomography (PET) probes. The radiochemical yield, specific activity, and radiochemical purity of these probes was appropriate for injection. To evaluate whether the brain penetration of these probes is related to the function of two major drug efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), we performed PET studies using wild-type and P gp/Bcrp knockout mice. In wild-type mice, the radioactivity level after injection with [(11)C]MBF initially increased and effluxed immediately from the brain, whereas that with [(11)C]JP-1302 was distributed throughout the brain. However, the regional distribution of radioactivity after injection with [(11)C]JP-1302 in the brain was different from that of alpha(2C)-ARs. In P-gp/Bcrp knockout mice, uptake of [(11)C]MBF was approximately 3.7-fold higher and that of [(11)C]JP-1302 was approximately 1.6-fold higher than those in wild-type mice. These results indicate that brain penetration of the two PET probes was affected by modulation of P-gp and Bcrp functions. PMID- 22778845 TI - ACS chemical neuroscience molecule spotlight on semagacestat (LY450139). AB - Semagacestat (LY450139) is a novel gamma-secretase inhibitor currently in late stage development by Eli Lilly and Company as a potential treatment for Alzheimer's disease (AD). Semagacestat is currently being studied in two phase III clinical trials. PMID- 22778847 TI - ACS chemical neuroscience molecule spotlight on dimebon. AB - Dimebon (latrepirdine) is an antihistamine drug that has been used clinically in Russia since the early 1980s and is being studied jointly by Pfizer and Medivation for patients with Alzheimer's disease. The results from a pivotal Phase 3 clinical trial (CONNECTION) showed that Dimebon (latrepirdine) failed to meet its coprimary or secondary efficacy end points. PMID- 22778846 TI - Photochemically initiated intracellular astrocytic calcium waves in living mice using two-photon uncaging of IP(3). AB - We have developed a caged IP(3) analogue for two-photon photolysis in living animals. This probe is a cell permeable version and was coloaded with a fluorescent Ca(2+) dye into astrocytes in layer 1 of the somatosensory cortex of anesthetized mice. Two-photon irradiation of single cells at 720 nm produced rapid and robust increases in intracellular Ca(2+) concentrations monitored using two-photon microscopy at 950 nm. The photoevoked intracellular Ca(2+) waves were similar in magnitude to intrinsic signals in wild type mice. These waves did not propagate to other cells beyond the targeted astrocyte. In contrast, we observed intercellular astrocytic Ca(2+) waves in two mouse models of familial Alzheimer's disease. These data suggest that Alzheimer's might perturb gliotransmission but not IP(3) signaling per se in mouse models of the disease. PMID- 22778848 TI - A small molecule which protects newborn neurons. AB - New research identifies a small molecule providing a chemical scaffold which might be useful in the design of a new class of neuroprotective drugs. PMID- 22778849 TI - Synthesis and evaluation of novel chalcone derivatives with (99m)Tc/Re complexes as potential probes for detection of beta-amyloid plaques. AB - Four (99m)Tc-labeled chalcone derivatives and their corresponding rhenium analogues were tested as potential probes for imaging beta-amyloid plaques. The chalcones showed higher affinity for Abeta(1-42) aggregates than did (99m)Tc complexes. In sections of brain tissue from an animal model of AD, the four Re chalcones intensely stained beta-amyloid plaques. In biodistribution experiments using normal mice, (99m)Tc-BAT-chalcone ([(99m)Tc]17) displayed high uptake in the brain (1.48% ID/g) at 2 min postinjection. The radioactivity washed out from the brain rapidly (0.17% ID/g at 60 min), a highly desirable feature for an imaging agent. [(99m)Tc]17 may be a potential probe for imaging beta-amyloid plaques in Alzheimer's brains. PMID- 22778850 TI - Structure-activity relationships in peptide modulators of beta-amyloid protein aggregation: variation in alpha,alpha-disubstitution results in altered aggregate size and morphology. AB - Neuronal cytotoxicity observed in Alzheimer's disease (AD) is linked to the aggregation of beta-amyloid peptide (Abeta) into toxic forms. Increasing evidence points to oligomeric materials as the neurotoxic species, not Abeta fibrils; disruption or inhibition of Abeta self-assembly into oligomeric or fibrillar forms remains a viable therapeutic strategy to reduce Abeta neurotoxicity. We describe the synthesis and characterization of amyloid aggregation mitigating peptides (AAMPs) whose structure is based on the Abeta "hydrophobic core" Abeta(17-20), with alpha,alpha-disubstituted amino acids (alphaalphaAAs) added into this core as potential disrupting agents of fibril self-assembly. The number, positional distribution, and side-chain functionality of alphaalphaAAs incorporated into the AAMP sequence were found to influence the resultant aggregate morphology as indicated by ex situ experiments using atomic force microscopy (AFM) and transmission electron microscopy (TEM). For instance, AAMP 5, incorporating a sterically hindered alphaalphaAA with a diisobutyl side chain in the core sequence, disrupted Abeta(1-40) fibril formation. However, AAMP-6, with a less sterically hindered alphaalphaAA with a dipropyl side chain, altered fibril morphology, producing shorter and larger sized fibrils (compared with those of Abeta(1-40)). Remarkably, alphaalphaAA-AAMPs caused disassembly of existing Abeta fibrils to produce either spherical aggregates or protofibrillar structures, suggesting the existence of equilibrium between fibrils and prefibrillar structures. PMID- 22778851 TI - Oral treatment with the d-enantiomeric peptide D3 improves the pathology and behavior of Alzheimer's Disease transgenic mice. AB - Several lines of evidence suggest that the amyloid-beta-peptide (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD). Not only Abeta fibrils but also small soluble Abeta oligomers in particular are suspected to be the major toxic species responsible for disease development and progression. The present study reports on in vitro and in vivo properties of the Abeta targeting d enantiomeric amino acid peptide D3. We show that next to plaque load and inflammation reduction, oral application of the peptide improved the cognitive performance of AD transgenic mice. In addition, we provide in vitro data elucidating the potential mechanism underlying the observed in vivo activity of D3. These data suggest that D3 precipitates toxic Abeta species and converts them into nonamyloidogenic, nonfibrillar, and nontoxic aggregates without increasing the concentration of monomeric Abeta. Thus, D3 exerts an interesting and novel mechanism of action that abolishes toxic Abeta oligomers and thereby supports their decisive role in AD development and progression. PMID- 22778853 TI - ACS chemical neuroscience spotlight on CEP-1347. PMID- 22778854 TI - ASIC3 channels in multimodal sensory perception. AB - Acid-sensing ion channels (ASICs), which are members of the sodium-selective cation channels belonging to the epithelial sodium channel/degenerin (ENaC/DEG) family, act as membrane-bound receptors for extracellular protons as well as nonproton ligands. At least five ASIC subunits have been identified in mammalian neurons, which form both homotrimeric and heterotrimeric channels. The highly proton sensitive ASIC3 channels are predominantly distributed in peripheral sensory neurons, correlating with their roles in multimodal sensory perception, including nociception, mechanosensation, and chemosensation. Different from other ASIC subunit composing ion channels, ASIC3 channels can mediate a sustained window current in response to mild extracellular acidosis (pH 7.3-6.7), which often occurs accompanied by many sensory stimuli. Furthermore, recent evidence indicates that the sustained component of ASIC3 currents can be enhanced by nonproton ligands including the endogenous metabolite agmatine. In this review, we first summarize the growing body of evidence for the involvement of ASIC3 channels in multimodal sensory perception and then discuss the potential mechanisms underlying ASIC3 activation and mediation of sensory perception, with a special emphasis on its role in nociception. We conclude that ASIC3 activation and modulation by diverse sensory stimuli represent a new avenue for understanding the role of ASIC3 channels in sensory perception. Furthermore, the emerging implications of ASIC3 channels in multiple sensory dysfunctions including nociception allow the development of new pharmacotherapy. PMID- 22778856 TI - ACS chemical neuroscience molecule spotlight on latuda (lurasidone; SM-13,496). PMID- 22778855 TI - Chemosensory properties of the trigeminal system. AB - The capacity of cutaneous, including trigeminal endings, to detect chemicals is known as chemesthesis or cutaneous chemosensation. This sensory function involves the activation of nociceptor and thermoreceptor endings and has a protective or defensive function, as many of these substances are irritants or poisonous. However, humans have also developed a liking for the distinct sharpness or pungency of many foods, beverages, and spices following activation of the same sensory afferents. Our understanding of the cellular and molecular mechanisms of chemosensation in the trigeminal system has experienced enormous progress in the past decade, following the cloning and functional characterization of several ion channels activated by physical and chemical stimuli. This brief review attempts to summarize our current knowledge in this field, including a functional description of various sensory channels, especially TRP channels, involved in trigeminal chemosensitivy. Finally, some of these new findings are discussed in the context of the pathophysiology of trigeminal chemosensation, including pain, pruritus, migraine, cough, airway inflammation, and ophthalmic diseases. PMID- 22778858 TI - Y95 and E444 interaction required for high-affinity S-citalopram binding in the human serotonin transporter. AB - The human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT) is responsible for the reuptake of 5-HT following synaptic release, as well as for import of the biogenic amine into several non-5-HT synthesizing cells including platelets. The antidepressant citalopram blocks SERT and thereby inhibits the transport of 5-HT. To identify key residues establishing high-affinity citalopram binding, we have built a comparative model of hSERT and Drosophila melanogaster SERT (dSERT) based on the Aquifex aeolicus leucine transporter (LeuT(Aa)) crystal structure. In this study, citalopram has been docked into the homology model of hSERT and dSERT using RosettaLigand. Our models reproduce the differential binding affinities for the R- and S-isomers of citalopram in hSERT and the impact of several hSERT mutants. Species-selective binding affinities for hSERT and dSERT also can be reproduced. Interestingly, the model predicts a hydrogen bond between E444 in transmembrane domain 8 (TM8) and Y95 in TM1 that places Y95 in a downward position, thereby removing Y95 from a direct interaction with S citalopram. Mutation of E444D results in a 10-fold reduced binding affinity for S citalopram, supporting the hypothesis that Y95 and E444 form a stabilizing interaction in the S-citalopram/hSERT complex. PMID- 22778857 TI - Medicinal chemistry of competitive kainate receptor antagonists. AB - Kainic acid (KA) receptors belong to the group of ionotropic glutamate receptors and are expressed throughout in the central nervous system (CNS). The KA receptors have been shown to be involved in neurophysiological functions such as mossy fiber long-term potentiation (LTP) and synaptic plasticity and are thus potential therapeutic targets in CNS diseases such as schizophrenia, major depression, neuropathic pain and epilepsy. Extensive effort has been made to develop subtype-selective KA receptor antagonists in order to elucidate the physiological function of each of the five subunits known (GluK1-5). However, to date only selective antagonists for the GluK1 subunit have been discovered, which underlines the strong need for continued research in this area. The present review describes the structure-activity relationship and pharmacological profile for 10 chemically distinct classes of KA receptor antagonists comprising, in all, 45 compounds. To the medicinal chemist this information will serve as reference guidance as well as an inspiration for future effort in this field. PMID- 22778859 TI - The "specific" P-glycoprotein inhibitor Tariquidar is also a substrate and an inhibitor for breast cancer resistance protein (BCRP/ABCG2). AB - Tariquidar was developed as a specific inhibitor of the efflux transporter ABCB1. Recent positron emission tomographic brain imaging studies using [(11)C]tariquidar to measure ABCB1 (P-gp, P-glycoprotein) density in mice indicate that the inhibitor may not be as specific as previously thought. We examined its selectivity as an inhibitor and a substrate for the human transporters P-gp, breast cancer resistance protein (BCRP, ABCG2), and multidrug resistance protein 1 (MRP1, ABCC1). Our results show that at low concentrations, tariquidar acts selectively as an inhibitor of P-gp and also as a substrate of BCRP. At much higher concentrations (>=100 nM), tariquidar acts as an inhibitor of both P-gp and BCRP. Thus, the in vivo specificity of tariquidar depends on concentration and the relative density and capacity of P-gp vs BCRP. PMID- 22778860 TI - Discovery of a new class of ionotropic glutamate receptor antagonists by the rational design of (2S,3R)-3-(3-carboxyphenyl)-pyrrolidine-2-carboxylic acid. AB - The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1-5. In this article, we present the discovery of (2S,3R)-3-(3-carboxyphenyl)-pyrrolidine-2 carboxylic acid (1) based on a rational design process. Target compound 1 was synthesized by a stereoselective strategy in 10 steps from commercially available starting materials. Binding affinities of 1 at native ionotropic Glu receptors were determined to be in the micromolar range (AMPA, 51 MUM; KA, 22 MUM; NMDA 6 MUM), with the highest affinity for cloned homomeric KA receptor subtypes GluK1,3 (3.0 and 8.1 MUM, respectively). Functional characterization of 1 by two electrode voltage clamp (TEVC) electrophysiology at a nondesensitizing mutant of GluK1 showed full competitive antagonistic behavior with a K(b) of 11.4 MUM. PMID- 22778861 TI - ACS chemical neuroscience molecule spotlight on gilenya (fingolimod; FTY720). PMID- 22778863 TI - Quantum dot labeling of butyrylcholinesterase maintains substrate and inhibitor interactions and cell adherence features. AB - Butyrylcholinesterase (BChE) is the major acetylcholine hydrolyzing enzyme in peripheral mammalian systems. It can either reside in the circulation or adhere to cells and tissues and protect them from anticholinesterases, including insecticides and poisonous nerve gases. In humans, impaired cholinesterase functioning is causally involved in many pathologies, including Alzheimer's and Parkinson's diseases, trait anxiety, and post stroke conditions. Recombinant cholinesterases have been developed for therapeutic use; therefore, it is important to follow their in vivo path, location, and interactions. Traditional labeling methods, such as fluorescent dyes and proteins, generally suffer from sensitivity to environmental conditions, from proximity to different molecules or special enzymes which can alter them, and from relatively fast photobleaching. In contrast, emerging development in synthesis and surface engineering of semiconductor nanocrystals enable their use to detect and follow molecules in biological milieus at high sensitivity and in real time. Therefore, we developed a platform for conjugating highly purified recombinant human BChE dimers (rhBChE) to CdSe/CdZnS quantum dots (QDs). We report the development and characterization of highly fluorescent aqueous soluble QD-rhBChE conjugates, present maintenance of hydrolytic activity, inhibitor sensitivity, and adherence to the membrane of cultured live cells of these conjugates, and outline their advantageous features for diverse biological applications. PMID- 22778862 TI - Superparamagnetic iron oxide nanoparticles: promises for diagnosis and treatment of multiple sclerosis. AB - Smart superparamagnetic iron oxide nanoparticles (SPIONs) are the most promising candidate for theragnosis (i.e., diagnosis and treatment) of multiple sclerosis. A deep understanding of the dynamics of the in vivo neuropathology of multiple sclerosis can be achieved by improving the efficiency of various medical techniques (e.g., positron emission tomography and magnetic resonance imaging) using multimodal SPIONs. In this Review, recent advances and challenges in the development of smart SPIONs for theragnostic applications are comprehensively described. In addition, critical outlines of emerging developments are provided from the points of view of both clinicians and nanotechnologists. PMID- 22778864 TI - Cysteine thioesters as myelin proteolipid protein analogues to examine the role of butyrylcholinesterase in myelin decompaction. AB - Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disorder involving demyelination, axonal transection, and neuronal loss in the brain. Recent studies have indicated that active MS lesions express elevated levels of butyrylcholinesterase (BuChE). BuChE can hydrolyze a wide variety of esters, including fatty acid esters of protein. Proteolipid protein (PLP), an important transmembrane protein component of myelin, has six cysteine residues acylated, via thioester linkages, with fatty acids, usually palmitic, that contribute to the stability of myelin. Experimental chemical deacylation of PLP has been shown to lead to decompaction of myelin. Because of elevated levels of BuChE in active MS lesions and its propensity to catalyze the hydrolysis of acylated protein, we hypothesized that this enzyme may contribute to deacylation of PLP in MS, leading to decompaction of myelin and contributing to demyelination. To test this hypothesis, a series of increasing chain length (C2-C16) acyl thioester derivatives of N-acetyl-l-cysteine methyl ester were synthesized and examined for hydrolysis by human cholinesterases. All N-acetyl-l-cysteine fatty acyl thioester derivatives were hydrolyzed by BuChE but not by the related enzyme acetylcholinesterase. In addition, it was observed that the affinity of BuChE for the compound increased the longer the fatty acid chain, with the highest affinity for cysteine bound to palmitic acid. This suggests that the elevated levels of BuChE observed in active MS lesions could be related to the decompaction of myelin characteristic of the disorder. PMID- 22778865 TI - Infrared microspectroscopy: a multiple-screening platform for investigating single-cell biochemical perturbations upon prion infection. AB - Prion diseases are a group of fatal neurodegenerative disorders characterized by the accumulation of prions in the central nervous system. The pathogenic prion (PrP(Sc)) possesses the capability to convert the host-encoded cellular isoform of the prion protein, PrP(C), into nascent PrP(Sc). The present work aims at providing novel insight into cellular response upon prion infection evidenced by synchrotron radiation infrared microspectroscopy (SR-IRMS). This non-invasive, label-free analytical technique was employed to investigate the biochemical perturbations undergone by prion infected mouse hypothalamic GT1-1 cells at the cellular and subcellular level. A decrement in total cellular protein content upon prion infection was identified by infrared (IR) whole-cell spectra and validated by bicinchoninic acid assay and single-cell volume analysis by atomic force microscopy (AFM). Hierarchical cluster analysis (HCA) of IR data discriminated between infected and uninfected cells and allowed to deduce an increment of lysosomal bodies within the cytoplasm of infected GT1-1 cells, a hypothesis further confirmed by SR-IRMS at subcellular spatial resolution and fluorescent microscopy. The purpose of this work, therefore, consists of proposing IRMS as a powerful multiscreening platform, drawing on the synergy with conventional biological assays and microscopy techniques in order to increase the accuracy of investigations performed at the single-cell level. PMID- 22778866 TI - ACS chemical neuroscience molecule spotlight on Qnexa. AB - Qnexa (VI-0521) is an investigational fixed-dose combination drug of phentermine and topiramate currently in Phase III clinical trials for the treatment of obesity. Vivus, Inc. has demonstrated efficacy of their product and are currently addressing FDA safety concerns with the possibility of a New Drug Application (NDA) resubmission. PMID- 22778867 TI - IUPHAR-DB: an open-access, expert-curated resource for receptor and ion channel research. AB - This contribution highlights efforts by the International Union of Basic and Clinical Pharmacology (IUPHAR) Nomenclature Committee (NC-IUPHAR) to classify human receptors and ion channels, to document their properties, and to recommend ligands that are useful for characterization. This effort has inspired the creation of an online database (IUPHAR-DB), which is intended to provide free information to all scientists, summarized from primary literature by experts. PMID- 22778868 TI - Molecular engineering of a secreted, highly homogeneous, and neurotoxic abeta dimer. AB - Abeta oligomers play a key role in the pathophysiology of Alzheimer's disease. Research into structure-function relationships of Abeta oligomers has been hampered by the lack of large amounts of homogeneous and stable material. Using computational chemistry, we designed conservative cysteine substitutions in Abeta aiming at accelerating and stabilizing assembly of Abeta dimers by an intermolecular disulfide bond without changing its folding. Molecular dynamics simulations suggested that mutants AbetaS8C and AbetaM35C exhibited structural properties similar to those of Abeta wildtype dimers. Full length, mutant APP was stably expressed in transfected cell lines to study assembly of Abeta oligomers in the physiological, secretory pathway and to avoid artifacts resulting from simultaneous in vitro oxidation and aggregation. Biochemical and neurophysiological analysis of supernatants indicated that AbetaS8C generated an exclusive, homogeneous, and neurotoxic dimer, whereas AbetaM35C assembled into dimers, tetramers, and higher oligomers. Thus, molecular engineering enabled generation of bioactive, homogeneous, and correctly processed Abeta dimers in vivo. PMID- 22778870 TI - The top prescription drugs of 2010 in the United States: antipsychotics show strong growth. PMID- 22778869 TI - Rhodanine and thiohydantoin derivatives for detecting tau pathology in Alzheimer's brains. AB - A novel series of rhodanin (RH) and thiohydantoin (TH) derivatives were designed and synthesized for detecting tau pathology in the brains of patients with Alzheimer's disease (AD). In experiments in vitro using tau and beta-amyloid (Abeta) aggregates, the TH derivative, TH2, showed high specific binding to tau aggregates. In hippocampal sections obtained from AD patients, TH2 intensely stained neurofibrillary tangles. In experiments using normal mice, [(125)I]TH2 showed good uptake (1.54%ID/g, 2 min postinjection) into and a rapid washout (0.25%ID/g, 60 min postinjection) from the brain. [(123)I]TH2 should be further investigated as a potential imaging agent for detecting tau pathology. PMID- 22778871 TI - ACS chemical neuroscience molecule spotlight on ELND006: another gamma-secretase inhibitor fails in the clinic. AB - ELND006 is a novel gamma-secretase inhibitor by Elan Corporation that was in the clinic as a potential treatment for Alzheimer's disease (AD). The clinical trial for ELND006 was halted in October 2010 due to liver side effects that are thought to be unrelated to the mechanism of action. However, this represents another small molecule gamma-secretase inhibitor that has failed in clinical trials (semagacestat) (http://newsroom.lilly.com/releasedetail.cfm?releaseid=499794) which raises serious questions regarding this mechanism for the treatment of AD. PMID- 22778872 TI - Binding modes of thioflavin T molecules to prion peptide assemblies identified by using scanning tunneling microscopy. AB - The widely used method to monitor the aggregation process of amyloid peptide is thioflavin T (ThT) assay, while the detailed molecular mechanism is still not clear. In this work, we report here the direct identification of the binding modes of ThT molecules with the prion peptide GNNQQNY by using scanning tunneling microscopy (STM). The assembly structures of GNNQQNY were first observed by STM on a graphite surface, and the introduction of ThT molecules to the surface facilitated the STM observations of the adsorption conformations of ThT with peptide strands. ThT molecules are apt to adsorb on the peptide assembly with beta-sheet structure and oriented parallel with the peptide strands adopting four different binding modes. This effort could benefit the understanding of the mechanisms of the interactions between labeling species or inhibitory ligands and amyloid peptides, which is keenly needed for developing diagnostic and therapeutic approaches. PMID- 22778873 TI - Point mutations in Abeta induce polymorphic aggregates at liquid/solid interfaces. AB - A pathological hallmark of Alzheimer's disease (AD), a late onset neurodegenerative disease, is the development of neuritic amyloid plaques, composed predominantly of aggregates of the beta-amyloid (Abeta) peptide. It has been demonstrated that Abeta can aggregate into a variety of polymorphic aggregate structures under different chemical environments, and a potentially important environmental factor in dictating aggregate structure is the presence of surfaces. There are also several mutations clustered around the central hydrophobic core of Abeta (E22G Arctic mutation, E22K Italian mutation, D23N Iowa mutation, and A21G Flemish mutation). These mutations are associated with hereditary diseases ranging from almost pure cerebral amyloid angiopathy (CAA) to typical Alzheimer's disease pathology. The goal of this study was to determine how these mutations influence the morphology of Abeta aggregates under free solution conditions and at an anionic surface/liquid interface. While the rate of formation of specific aggregates was altered by mutations in Abeta under free solution conditions, the respective aggregate morphologies were similar. However, aggregation occurring directly on a negatively charged mica surface resulted in distinct aggregate morphologies formed by different mutant forms of Abeta. These studies provide insight into the potential role anionic surfaces play in dictating the formation of Abeta polymorphic aggregate structures. PMID- 22778875 TI - Epidemiology of prostate cancer and treatment remarks. AB - Prostate cancer is one of the most common types of cancer and one of the leading causes of cancer death among men in the Western countries. The aim of the present analysis is to assess the cancer burden in order to ensure accurate strategies for chemoprevention and treatment, including the major therapeutic approaches for localized high-risk disease - surgery and radiation therapy - and quality of life issues related to each option. PMID- 22778876 TI - Ultrasound- and MR-guided focused ultrasound surgery for prostate cancer. AB - Prostate cancer (PC) is one of the most frequently diagnosed cancers in men. There are a number of treatment options for PC with a different therapeutic approach between USA and Europe. Radical prostatectomy is one of the most used therapies but focal gland therapy is an emerging approach, especially for localized tumors. In this scenario, high intensity focused ultrasound (HIFU) has been incorporated in certain medical association guidelines. HIFU has been employed for about 10 years especially for localized PC. Results are promising with a 5-year biochemical survival rate ranging from 45% to 84%. Collateral events are rare and HIFU retreatment is not common. Magnetic resonance guided focused ultrasound surgery (MRgFUS) was recently presented as a method for ablation with focused ultrasound under magnetic resonance imaging guidance. It has the advantage of improved targeting and real time temperature monitoring but only a few studies have been conducted with human patients. The aim of this review is to describe the current status of HIFU and MRgFUS in the therapy of PC. PMID- 22778874 TI - Cross-receptor interactions between dopamine D2L and neurotensin NTS1 receptors modulate binding affinities of dopaminergics. AB - Dopaminergic systems have been described to functionally interact with the neuromodulatory peptide neurotensin. Employing fluorescence detected coimmunoprecipitation and radioligand binding experiments, we herein demonstrate that coexpression of dopamine D(2L) receptor and the neurotensin receptor subtype NTS(1) leads to physical interaction and the formation of heteromers in transfected human embryonic kidney 293 cells. In this in vitro system, a trans inhibitory effect on the agonist binding affinity of D(2) was observed in presence of neurotensin. To correlate between the functional properties of dopaminergic agents and the magnitude of neurotensin-induced modulation of D(2L) binding affinities in cells coexpressing D(2L) and NTS(1), a structurally diverse set of dopamine receptor agonists, partial agonists, and antagonists was tested. Ligand specific profiles indicating substantial bias between ligand efficacy and transmodulation were discovered, suggesting a heteromerization-based functional selectivity. In the presence of neurotensin, the novel D(2) agonist FAUC 326 displayed a 34-fold decrease of binding affinity in cells coexpressing D(2L) and NTS(1). PMID- 22778877 TI - Patient selection and preparation strategies for the use of contrast material in patients with chronic kidney disease. AB - The prevalence of chronic kidney disease and peripheral arterial disease is increasing. Thus, it is increasingly problematic to image these patients as the number of patients needing a vascular examination is increasing accordingly. In high-risk patients with impaired kidney function, intravascular administration of iodinated contrast media can result in contrast-induced acute kidney injury and Gadolinium can induce nephrogenic systemic fibrosis (NSF). It is important to identify these high-risk patients by means of se-creatinine/e glomerular filtration rate. The indication for contrast examination should counterbalance the increased risk. One or more alternative examination methods without contrast media, such as CO(2) angiography, Ultrasound/Doppler examination or magnetic resonance angiography without contrast should be considered, but at the same time, allow for a meaningful outcome of the examination. If contrast is deemed essential, the patient should be well hydrated, the amount of contrast should be restricted, the examination should be focused, metformin and diuretics stopped, and renal function monitored. Sodium bicarbonate and N-acetylcysteine are popular but their efficiency is not evidence-based. There is no evidence that dialysis protects patients with impaired renal function from contrast-induced nephropathy or NSF. PMID- 22778878 TI - Dual source computed tomography coronary angiography in new onset cardiomyopathy. AB - AIM: To evaluate safety and utility of coronary computed tomography angiography (CCTA) compared to invasive coronary angiography (ICA) in new cardiomyopathy. METHODS: Eighteen patients (mean age 56.5 years, 10 males) who presented for evaluation of new onset heart failure with evidence of systolic dysfunction (ejection fraction < 40%) on echocardiography and recent ICA were prospectively enrolled. Patients with known coronary artery disease, atrial fibrillation, creatinine > 1.5 g/dL, and contraindication to intravenous contrast administration were excluded. CCTA was performed using a dual source 64-slice scanner. Mean heart rate was 75 beats per minute. Stenosis was graded for each coronary segment as: none, mild (< 50%), moderate (50%-70%), severe (> 70%), or non-evaluable. Ischemic cardiomyopathy (ICM) was diagnosed if severe stenosis was present in the left main, proximal left anterior descending artery, or two or more major arteries. RESULTS: Two patients were diagnosed with ICM by ICA. CCTA correctly identified 2 patients with ICM and 16 patients as non-ICM. CCTA successfully evaluated 240/246 coronary segments with an accuracy of 97.5%, sensitivity 70%, specificity 98.7%, positive predictive value of 70%, and negative predictive value of 98.7% for identifying severe stenosis on a per segment level. CONCLUSION: Dual source 64-slice multi-detector CCTA is a safe, accurate, and non-invasive technique for diagnosing ICM in patients presenting during the acute phase of newly diagnosed cardiomyopathy. PMID- 22778879 TI - Plaque imaging with CT coronary angiography: Effect of intra-vascular attenuation on plaque type classification. AB - AIM: To assess the attenuation of non-calcified atherosclerotic coronary artery plaques with computed tomography coronary angiography (CTCA). METHODS: Four hundred consecutive patients underwent CTCA (Group 1: 200 patients, Sensation 64 Cardiac, Siemens; Group 2: 200 patients, VCT GE Healthcare, with either Iomeprol 400 or Iodixanol 320, respectively) for suspected coronary artery disease (CAD). CTCA was performed using standard protocols. Image quality (score 0-3), plaque (within the accessible non-calcified component of each non-calcified/mixed plaque) and coronary lumen attenuation were measured. Data were compared on a per segment/per-plaque basis. Plaques were classified as fibrous vs lipid rich based on different attenuation thresholds. A P < 0.05 was considered significant. RESULTS: In 468 atherosclerotic plaques in Group 1 and 644 in Group 2, average image quality was 2.96 +/- 0.19 in Group 1 and 2.93 +/- 0.25 in Group 2 (P >= 0.05). Coronary lumen attenuation was 367 +/- 85 Hounsfield units (HU) in Group 1 and 327 +/- 73 HU in Group 2 (P < 0.05); non-calcified plaque attenuation was 48 +/- 23 HU in Group 1 and 39 +/- 21 HU in Group 2 (P < 0.05). Overall signal to noise ratio was 15.6 +/- 4.7 in Group 1 and 21.2 +/- 7.7 in Group 2 (P < 0.01). CONCLUSION: Higher intra-vascular attenuation modifies significantly the attenuation of non-calcified coronary plaques. This results in a more difficult characterization between lipid rich vs fibrous type. PMID- 22778880 TI - Evaluation of vascular puncture needles with specific modifications for enhanced ultrasound visibility: In vitro study. AB - AIM: To determine which modification to a vascular puncture needle results in increased visualization during ultrasound (US)-guided vascular puncture. METHODS: We evaluated US images of a phantom made of degassed gelatin and each of the following four modified versions of a commercially available vascular puncture needle (18 G): re-cut needle, dimple needle, rough-surface needle (rough over the sections of needle located 3-6 mm from the tip), and a needle with four side holes (side holes covered by the sheath). An unmodified commercially available puncture needle was used as a control. Five interventional radiologists evaluated image quality according to the following classification grade: I, invisible; II, poor; III, moderate; IV, good; V, excellent. RESULTS: The highest score for needle visualization was obtained for the needle with four side holes. The re-cut needle scored the same as the control. Multiple comparisons were conducted using overall evaluation scores among the commercially available needle, dimple needle, rough-surface needle (3-6 mm), and the needle with four side holes. A significantly higher score was obtained for the needle with four side holes (P < 0.05/6). CONCLUSION: The needle with four side holes was prominently visualized and gained a significantly higher score (compared with the other needles) in a phantom evaluation. PMID- 22778881 TI - CT-guided radiofrequency ablation of osteoid osteoma in the long bones of the lower extremity. AB - AIM: To present our initial experience with computed tomography guided radiofrequency ablation (RFA) of osteoid osteoma (OO) in our institution. METHODS: RFA was performed on eight patients (5 males and 3 females) with clinically and radiologically diagnosed OO (femoral neck, n = 4; femoral diaphysis, n = 2; tibial diaphysis, n = 1; fibular diaphysis, n = 1). Ablation was performed using an electrode with a 10-mm exposed tip for a total of 4-6 min at a targeted temperature of 90 degrees Celsius. No cooling system was used. The intervention was accepted as technically successful if the tip of the electrode could be placed within the center of the nidus. We defined clinical success as a disappearance within 2 wk after treatment of symptoms that had manifested at presentation. RESULTS: All procedures were technically successful. No major or immediate complications were observed. Clinical success was achieved in six of eight patients in the first procedure. A second procedure was performed for two patients who had recurrent or continued pain, and one of these cases was successfully treated. The overall rate of success was 87.5% (7/8). No complication was observed. CONCLUSION: Our preliminary results indicate a favorable success rate and no complications and are compatible with the previous reports of RFA of OO. PMID- 22778882 TI - Two rare cases of craniofacial chondrosarcoma. AB - The craniofacial region is a rare site for chondrosarcomas. These tumors may have osseous or extraosseous origin. Extraosseous chondrosarcomas have the same histological features as osseous chondrosarcomas. Chondrosarcomas usually present in the fifth to seventh decades of life, although several cases with younger age at presentation have been reported. They usually present as a painless mass that gradually progresses to various complaints, such visual impairment, nasal obstruction, and dental abnormalities. In this article, we present two cases of chondrosarcoma occurring at rather unusual locations. It is important to keep this rare malignancy in the list of differential diagnoses for a mass in the head and neck region, as these tumors may not always show the features typical of this malignancy. PMID- 22778883 TI - Skull metastasis in papillary carcinoma of thyroid: A case report. AB - Papillary thyroid carcinoma with metastasis to the skull is extremely rare. We report a case of unsuspected papillary thyroid carcinoma with skull metastasis. A 48-year-old female patient presenting with painless, pulsatile, progressively increasing swelling in the occipitoparietal region of the scalp approached for an X-ray of the skull. Ultrasound of palpable swelling in the neck revealed a heteroechoic lesion with increased vascularity. Foci of calcification were seen involving both lobes of the thyroid. Ultrasound of scalp showed a destructive mass in the skull with increased vascularity. Biopsy of thyroid lesions revealed branching papillae having a dense fibrovascular core covered by cuboidal epithelial cells with nuclei having a clear ground glass appearance. This case illustrates how isolated extensive skull metastasis can be found in papillary carcinoma patients without causing significant morbidity. Therefore, in the clinical course of thyroid papillary carcinoma, skull metastasis should be considered, and the patients should be meticulously investigated and followed up. PMID- 22778884 TI - About uses of magnesium during perioperative period. PMID- 22778885 TI - Sufentanil infusion before extubation suppresses coughing on emergence without delaying extubation time and reduces postoperative analgesic requirement without increasing nausea and vomiting after desflurane anesthesia. AB - BACKGROUND: Coughing, hypertension, tachycardia, and even laryngospasm can occur due to airway irritation during emergence from anesthesia. We investigated the effect of maintaining a sufentanil infusion during emergence from anesthesia by evaluating the incidence of cough and recovery profiles at extubation. METHODS: In total, eighty-four patients undergoing an elective laparoscopic hysterectomy were randomly divided into two sufentanil groups and a control group. During emergence, sufentanil was administered in the sufentanil groups at a rate of 0.2 ug/kg/hr (Group S1) or 0.3 ug/kg/hr (Group S2), and saline was administered to the control group. Cough score, hemodynamic changes, and recovery profiles, such as duration from skin closure to a bispectral index of 80, to eye opening at verbal command, to tracheal extubation and the total duration of study solution infusion, were recorded. The pain score, the total volume of administered patient controlled analgesia (PCA), and the postoperative nausea and vomiting (PONV) score were evaluated 1, 6, and 24 hours after surgery. RESULTS: Groups S1 and S2 showed significantly lower cough scores and smaller hemodynamic changes on extubation compared to Group C. Recovery profiles showed no significant differences among the three groups. Pain score, PONV at 1 hour postoperatively, and the total volume of PCA administered at all evaluation times were significantly lower in Groups S1 and S2 than in the control group. However, pain score, and PONV at 6 hours and 24 hours postoperatively showed no significant differences. CONCLUSIONS: A sufentanil infusion (0.2-0.3 ug/kg/hr) during emergence from desflurane anesthesia may suppress coughing on extubation in patients with body mass indexes (BMI) of 21-26 without delaying extubation time. It may also reduce the postoperative analgesic requirement without increasing PONV. PMID- 22778886 TI - Effect of magnesium sulfate pretreatment on onset and recovery characteristics of cisatracurium. AB - BACKGROUND: To determine how pretreatment with magnesium sulfate (MgSO(4)) potentiates neuromuscular blocking agents. We investigated how the onset and recovery characteristics of cisatracurium are changed by pretreatment with MgSO(4). METHODS: After Institutional Review Board approval, a total of 48 ASA I and II patients were devided into 2 groups. Patients in each group received either the MgSO(4) 30 mg/kg (group M) in 0.9% normal saline (total volume 100 ml) or 0.9% normal saline (control group C) alone intravenously for 15 min before induction of anesthesia with propofol, remifentanil and cisatracurium 0.15 mg/kg. Anesthesia was maintained with propofol and remifentanil. Electromyographical responses were measured by train-of-four. Lag time, onset time, total recovery time, clinical duration, recovery index, and recovery time were measured. The mean arterial blood pressure, heart rate, and ionized magnesium were also measured. RESULTS: The lag time and onset time were significantly shorter in the MgSO(4) group than the control group (P < 0.05). Recovery index, recovery time, clinical duration, and total recovery time showed no significant differences in the MgSO(4) group compared to the control group (P > 0.05). Mean arterial pressure was more significantly increased in the MgSO(4) group than in the control group at the time point immediately after the administration of MgSO(4). Heart rate showed no significant changes in both groups. The concentrations of ionized magnesium were significantly more increased at the all time point (P < 0.05). CONCLUSIONS: MgSO(4) results in about 29% shortening of onset time of cisatracurium (0.15 mg/kg) without prolongation on the recovery of neuromuscular block. PMID- 22778887 TI - A simple method of partial inflation of the LMA cuff before insertion in children to allow cuff pressure without adjustment after insertion. AB - BACKGROUND: The cuff of the laryngeal mask airway (LMA) is preferred to be partially inflated before insertion in pediatric cases. However, it is not known how much inflation is appropriate. In addition, intra-cuff pressure is not routinely monitored in many institutions despite the fact that a neglected high cuff pressure could cause several complications. This study was conducted to determine whether the cuff inflated with its resting volume before insertion could have a clinically tolerable intra-cuff pressure after insertion. METHODS: One hundred fifty unpremedicated children aged 0 to 9 yrs were enrolled. The pilot balloon valve was connected to a piston-free syringe to keep the valve open to the atmosphere and allowing the pressure within the cuff of to LMA to equalize to atmospheric pressure. Anesthesia was induced with 6 vol% of sevoflurane in oxygen. After insertion and final positioning of the LMA, the intra-cuff pressure was measured using a cuff pressure manometer. RESULTS: The mean intra-cuff pressure was 50 +/- 12.9 cmH(2)O; intra-cuff pressures were 39.1 +/- 9.3, 51.6 +/ 11.2, and 64.6 +/- 12.5 cmH(2)O for LMAs of sizes 1.5, 2, and 2.5, respectively. Intra-cuff pressure of more than 60 cmH(2)O was measured in 26 patients, and the median value was 70 cmH(2)O. There was weak statistical correlation among age, height, and weight with intra-cuff pressure. CONCLUSIONS: The cuff inflated by the resting volume before insertion may be a simple method for guaranteeing tolerable cuff pressure after insertion. PMID- 22778888 TI - Effect of sevoflurane on grafted kidney function in renal transplantation. AB - BACKGROUND: The objective of this retrospective study was to determine if there are any differences in grafted kidney function in recipients of kidney transplantation (KT) when donors and recipients were anesthetized with sevoflurane compared to desflurane. METHODS: Seventy-three pairs of donors recipients were anesthetized with sevoflurane (Sevo group) and 71 pairs were anesthetized with desflurane (Des group). We retrospectively investigated the blood urea nitrogen (BUN) levels, creatinine (Cr) levels, and estimated glomerular filtration rates (eGFR) of the recipients in both groups for 1 year postoperatively. We tested non-inferiority for serum creatinine at discharge and 1 year after KT. Short-term (1 year) outcomes of KT were assessed by the incidence of delayed graft function (DGF), acute rejection episodes (ARE), and graft failure. RESULTS: There were no differences in BUN, Cr, eGFR, or outcomes of KT at 1 year postoperatively. Specifically, the 95% confidence interval for the difference in creatinine levels between the Sevo and Des groups was less than the margin of equivalence at the time of discharge and 1 year after surgery. The occurrences of DGF, ARE, and graft failure were comparable between the groups. CONCLUSIONS: Compared to desflurane, sevoflurane had no adverse effects on grafted renal function or on the short-term outcome of renal transplantation. PMID- 22778889 TI - The cardiovascular effects of midazolam co-induction to propofol for induction in aged patients. AB - BACKGROUND: The aim of this study was to investigate whether a small dose of midazolam and lessening the propofol dosage could prevent cardiovascular change at tracheal intubation for induction in aged patients. METHODS: Eighty patients over 65 years (ASA physical status 1, 2) scheduled for elective surgery received general anesthesia with remifentanil and propofol or midazolam. Patients in group P (n = 40) were induced with 0.9% NaCl 0.03 ml/kg, propofol 1. 2 mg/kg and remifentanil. Patients in group MP (n = 40) were induced with midazolam 0.03 mg/kg, propofol 0.8 mg/kg and remifentanil. The time taken to reach loss of consciousness (LOC) and the value of bispectral index score (BIS) at LOC were recorded. After LOC, 0.8 mg/kg of rocuronium was given and tracheal intubation was performed. The mean blood pressure (MBP) and heart rate (HR) were recorded before induction as the base value, before intubation, immediately post intubation and 3 minutes after intubation. RESULTS: Compared with the base values, MBP at before intubation and 3 minutes after intubation was significantly decreased in group P and group MP (P < 0.05). Compared with group P, the decrease of MBP was significantly less at before intubation, immediately after intubation and 3 minutes after intubation in group MP (P < 0.05). The time taken to reach LOC was significantly decreased in group MP compared with that in group P (P < 0.05). There were no significant differences of HR at any time between the two groups. CONCLUSIONS: Co-induction with midazolam and propofol could prevent a marked BP decrease at tracheal intubation for induction in aged patients. PMID- 22778890 TI - Efficacy comparison of ramosetron with ondansetron on preventing nausea and vomiting in high-risk patients following spine surgery with a single bolus of dexamethasone as an adjunct. AB - BACKGROUND: Despite the development of a new class of antiemetics, postoperative nausea and vomiting (PONV) still remains a frequent and distressing complication. We compared the prophylactic antiemetic effect of administering dexamethasone 5 mg as an adjunct to ramosetron and ondansetron in patients at high-risk for PONV following lumbar spinal surgery. METHODS: In this randomized, double-blind study, 120 female non-smoking patients with intravenous patient-controlled analgesia (PCA) received ramosetron 0.3 mg plus dexamethasone 5 mg (group R + D) or ondansetron 4 mg plus dexamethasone 5 mg (group O + D) intravenously. Fentanyl based PCA was administered for 48 hr postoperatively; ramosetron 0.3 mg or ondansetron 12 mg was added to the PCA regimen according to the allocated group. The incidence of PONV and rescue antiemetic were assessed for 48 hr postoperatively at 0-6, 6-24, and 24-48 hr. RESULTS: The overall incidence of PONV did not differ between the groups (50% vs. 60%, in groups R + D and O + D, respectively). The overall incidence of nausea was similar between groups (47% vs. 60%, in groups R + D and O + D, respectively). The overall frequency of vomiting was also similar between groups (8% vs. 12%, in groups R + D and O + D, respectively). The severity of nausea and the overall use of rescue antiemetic were not different between groups. CONCLUSIONS: The antiemetic efficacy of ramosetron plus dexamethasone was similar to that of ondansetron plus dexamethasone on preventing PONV in high-risk patients undergoing lumbar spinal surgery. PMID- 22778891 TI - The willingness of patients to pay for intravenous patient-controlled analgesia in Korea. AB - BACKGROUND: The use of intravenous patient-controlled analgesia (IV-PCA) has been increasing because it has advantages such as improved pain relief, greater patient satisfaction, and fewer postoperative complications. However, current research has not considered the patients' thoughts about IV-PCA's cost effectiveness. The purpose of this study was to investigate the willingness to pay (WTP) for IV-PCA and the relationship between patients' characteristics and WTP in Korea. METHODS: We enrolled 400 adult patients who were scheduled for elective surgery. The patient was requested to indicate a series of predefined amounts of money (Korean won; 30,000/50,000/100,000/150,000/200,000/300,000/500,000). We also recorded patient characteristics, such as age, sex, type of surgery, IV-PCA history, education level, the person responsible for medical expenses, type of insurance, net annual income, and residential area. Three days after surgery, we asked about the degree of satisfaction and the WTP for IV-PCA. RESULTS: For IV-PCA, the median WTP was 100,000 won (25-75%; 50,000-200,000 won: US$1 = W1078.04; July 19, 2011) before surgery. All patients' characteristics were not related to preoperative WTP for IV-PCA, whereas the increase in WTP after surgery showed a tendency correlated to higher IV-PCA satisfaction. CONCLUSIONS: The median WTP was 100,000 won. The satisfaction of IV-PCA increased patients' WTP after surgery, but the WTP may be independent of patient characteristics in Korea. PMID- 22778892 TI - The effects of lidocaine and procaine on microRNA expression of adipocyte-derived adult stem cells. AB - BACKGROUND: The microRNA (miRNA) pathway has emerged as one of the biologic pathways implicated in stem cell regulation. miRNA is a noncoding, single stranded RNA consisting of 20-25 nucleotides that inhibits the protein production at the step of translation. The molecular effects of lidocaine and procaine on adipose stem cells were investigated by examining RNA expression array. METHODS: Adipose stem cells were isolated from a prior abdominal liposuction procedure. The human adipose stem cells were cultured and then added to a mixture of 1 ml of culture medium plus 1 ml of 2% lidocaine or 2% procaine for the duration of 30 minutes. The expression levels of miRNAs were estimated by using peptide nucleic acid (PNA)-miRNA array analysis throughout the denaturation and hybridization processes after the isolation of miRNA. The miRNAs detected by microarray that either decreased by half fold or increased by 1.5 fold from the control level were interpreted as significant. RESULTS: According to microarray analysis there were 61 miRNAs in total, and no miRNA had decreased expression levels. The stem cells treatment with lidocaine showed 4 alteration of expression with miR-9a(*) (1.53 fold), miR-29a (1.64 fold), miR-296-5p (1.64 fold) and miR-373 (1.94 fold). The stem cells treated with procaine showed 32 miRNAs that were significantly up regulated with a range of 1.5 to 2.06 fold. They were stem cell differentiation related miRNAs, apoptosis and cell cycle-associated miRNAs, immunity-associated miRNAs and hormonal response-related miRNAs. CONCLUSIONS: Lidocaine and procaine affect the miRNA expression on adipose stem cells and the effect of procaine is more marked than that of lidocaine. PMID- 22778893 TI - Antinociceptive effect of phenyl N-tert-butylnitrone, a free radical scavenger, on the rat formalin test. AB - BACKGROUND: Reactive oxygen species (ROS) such as superoxide radicals, hydrogen peroxide, nitric oxide, and nitroperoxide, cause oxidative stress which interferes with normal cell functioning, resulting in cell damage. It is reported to be associated with chronic pain, especially neuropathic pain, and inflammatory pain. ROS is also closely related to central sensitization. Therefore, this study was designed to explore the effects of Phenyl N-tert-butylnitrone (PBN), an ROS scavenger, in acute, continuous, and increasing pain caused by central sensitization. METHODS: Male Sprague-Dawley rats were divided into 2 groups, an intraperitoneal group (IP) and an intrathecal group (IT), and once again divided into an experimental group and a control group. The experimental group was injected with Phenyl N-tert-butylnitrone (PBN), a free radical scavenger, either intraperitoneally or intrathecally. After inducing pain by injecting formalin into the hind paw, pain behaviors were measured. Lumbar enlargement immmunohistochemistry was performed to assess nitrotyrosine, an oxidative stress marker, to identify the degree of protein nitration. RESULTS: Both experimental groups of IP and IT showed statistically significant decreases in the number of flinches compared to the control group in phase 1 and 2. Immunohistochemical evaluation in the control group revealed an increase in nitrated proteins in the gray matter of the lumbar spinal cord, but a significant decrease in nitrated proteins in the gray matter of lumbar spinal cord of the experimental group. CONCLUSIONS: Intraperitoneal and intrathecal administration of PBN decreases analgesic behaviors, allowing us to believe that ROS is mainly responsible for acute pain and central sensitization. PMID- 22778894 TI - Placement of a double-lumen tube using LMA C Trach and an exchanger catheter in difficult airway intubation -A case report-. AB - During insertion of the double lumen tube in patients with cervical vertebral fixation, the cervical neutral position should be maintained. Although flexible fiberoptic bronchoscopic intubation is the gold standard, novel techniques are needed to facilitate intubation of patients with cervical vertebral fixation in neutral position according to institutional capabilities. In this case report, insertion of the double lumen tube in the neutral position using LMA CTrach and an airway exchanger catheter in a thoracotomy patient with extremely limited head and neck motion due to fixation of the cervical vertebrae is presented. PMID- 22778895 TI - Ultrasound-guided interscalene brachial plexus block in a pediatric patient with acute hepatitis -A case report-. AB - The interscalene brachial plexus block is not commonly used in pediatric regional anesthesia. The increasing popularity of ultrasound has allowed more anesthesiologists to perform regional anesthesia with high success rates in pediatric patients with the direct visualization of the target nerve and spread of local anesthetics. We present a case of interscalene brachial plexus block under ultrasound guidance in a 17-month-old child with acute drug-induced hepatitis who required fixation of a fracture of the lateral humeral condyle. PMID- 22778896 TI - Formation of intracardiac thrombus during cardiopulmonary bypass despite full heparinization and adequate activated clotting time -A case report-. AB - We reports a case of a newly formed thrombus in the left atrial appendage during cardiopulmonary bypass detected by transesophageal echocardiography in a patient with chronic atrial fibrillation and mitral stenosis. This case alerts the anesthesiologists of possible thrombus formation despite full heparinization during cardiac surgery and the importance of a comprehensive echocardiography examination. PMID- 22778897 TI - Anesthetic management of HELLP syndrome complicating primary antiphospholipid syndrome -A case report-. AB - Antiphospholipid syndrome (APS) is defined as an autoimmune disorder characterized by recurrent thrombosis or obstetrical morbidity. A 29-year-old woman who was diagnosed with APS underwent emergency cesarean delivery at 23 weeks' gestation. She had a seizure attack and her laboratory findings were: AST/ALT 1459/1108 IU/L, LDH 1424 IU/L, 30% hematocrit, a platelet count of 43 * 10(3)/ml and urine protein (4+). We describe the anesthetic experience of catastrophic HELLP syndrome with antiphospholipid syndrome and we review the relevant literature. PMID- 22778898 TI - Anesthetic management of a parturient for combined cesarean section and surgical removal of pituitary tumor -A case report-. AB - A 40-year-old woman was referred to our hospital because of bitemporal hemianopsia at 23 weeks of gestation. A brain magnetic resonance imaging showed a pituitary tumor having suprasellar extension. At 30 weeks of gestation, she complained of rapidly deteriorating vision and bitemporal hemianopsia in both eyes and the ensuing radiological examination revealed increased tumor size, displaced tumor location and compressed optic chiasm. The cesarean section was performed at 31 weeks and 3 days of gestation and simultaneous surgical removal of pituitary tumor was carried out due to the risk of irreversible blindness. Anesthetic management for combined cesarean section and brain surgery can be more complex and challenging for anesthesiologists, and the aim was to achieve both the control of intracranial pressure and fetal well being at the same time. In this case, maternal outcome was somewhat improved after the procedure, and neonatal complications were not detected. PMID- 22778899 TI - Anesthetic considerations during heart-lung transplantation in a patient with an unresectable pulmonary artery sarcoma. PMID- 22778900 TI - Endotracheal tube fire during tracheostomy. PMID- 22778901 TI - Metagenomes of Mediterranean coastal lagoons. AB - Coastal lagoons, both hypersaline and freshwater, are common, but still understudied ecosystems. We describe, for the first time, using high throughput sequencing, the extant microbiota of two large and representative Mediterranean coastal lagoons, the hypersaline Mar Menor, and the freshwater Albufera de Valencia, both located on the south eastern coast of Spain. We show there are considerable differences in the microbiota of both lagoons, in comparison to other marine and freshwater habitats. Importantly, a novel uncultured sulfur oxidizing Alphaproteobacteria was found to dominate bacterioplankton in the hypersaline Mar Menor. Also, in the latter prokaryotic cyanobacteria were almost exclusively comprised by Synechococcus and no Prochlorococcus was found. Remarkably, the microbial community in the freshwaters of the hypertrophic Albufera was completely in contrast to known freshwater systems, in that there was a near absence of well known and cosmopolitan groups of ultramicrobacteria namely Low GC Actinobacteria and the LD12 lineage of Alphaproteobacteria. PMID- 22778902 TI - Disintegrins from hematophagous sources. AB - Bloodsucking arthropods are a rich source of salivary molecules (sialogenins) which inhibit platelet aggregation, neutrophil function and angiogenesis. Here we review the literature on salivary disintegrins and their targets. Disintegrins were first discovered in snake venoms, and were instrumental in our understanding of integrin function and also for the development of anti-thrombotic drugs. In hematophagous animals, most disintegrins described so far have been discovered in the salivary gland of ticks and leeches. A limited number have also been found in hookworms and horseflies, and none identified in mosquitoes or sand flies. The vast majority of salivary disintegrins reported display a RGD motif and were described as platelet aggregation inhibitors, and few others as negative modulator of neutrophil or endothelial cell functions. This notably low number of reported disintegrins is certainly an underestimation of the actual complexity of this family of proteins in hematophagous secretions. Therefore an algorithm was created in order to identify the tripeptide motifs RGD, KGD, VGD, MLD, KTS, RTS, WGD, or RED (flanked by cysteines) in sialogenins deposited in GenBank database. The search included sequences from various blood-sucking animals such as ticks (e.g., Ixodes sp., Argas sp., Rhipicephalus sp., Amblyommasp.), tabanids (e.g., Tabanus sp.), bugs (e.g., Triatoma sp., Rhodnius prolixus), mosquitoes (e.g., Anopheles sp., Aedes sp., Culex sp.), sand flies (e.g., Lutzomyia sp., Phlebotomus sp.), leeches (e.g., Macrobdella sp., Placobdella sp.) and worms (e.g., Ancylostoma sp.). This approach allowed the identification of a remarkably high number of novel putative sialogenins with tripeptide motifs typical of disintegrins (>450 sequences) whose biological activity remains to be verified. This database is accessible online as a hyperlinked worksheet and displays biochemical, taxonomic, and gene ontology aspects for each putative disintegrin. It is also freely available for download (right click with the mouse) at links http://exon.niaid.nih.gov/transcriptome/RGD/RGD-Peps-WEB.xlsx (web version) and http://exon.niaid.nih.gov/transcriptome/RGD/RGD-sialogenins.zip (stand alone version). PMID- 22778903 TI - Cytotoxicity and glycan-binding properties of an 18 kDa lectin isolated from the marine sponge Halichondria okadai. AB - A divalent cation-independent lectin-HOL-18, with cytotoxic activity against leukemia cells, was purified from a demosponge, Halichondria okadai. HOL-18 is a 72 kDa tetrameric lectin that consists of four non-covalently bonded 18 kDa subunits. Hemagglutination activity of the lectin was strongly inhibited by chitotriose (GlcNAcbeta1-4GlcNAcbeta1-4GlcNAc), fetuin and mucins from porcine stomach and bovine submaxillary gland. Lectin activity was stable at pH 4-12 and temperatures lower than 60 degrees C. Frontal affinity chromatography with 16 types of pyridylaminated oligosaccharides indicated that the lectin had an affinity for N-linked complex-type and sphingolipid-type oligosaccharides with N acetylated hexosamines and neuramic acid at the non-reducing termini. The lectin killed Jurkat leukemia T cells and K562 erythroleukemia cells in a dose- and carbohydrate-dependent manner. PMID- 22778904 TI - Single laboratory validation of a ready-to-use phosphatase inhibition assay for detection of okadaic acid toxins. AB - A phosphatase inhibition assay for detection of okadaic acid (OA) toxins in shellfish, OkaTest, was single laboratory validated according to international recognized guidelines (AOAC, EURACHEM). Special emphasis was placed on the ruggedness of the method and stability of the components. All reagents were stable for more than 6 months and the method was highly robust under normal laboratory conditions. The limit of detection and quantification were 44 and 56 ug/kg, respectively; both below the European legal limit of 160 ug/kg. The repeatability was evaluated with 2 naturally contaminated samples. The relative standard deviation (RSD) calculated was 1.4% at a level of 276 ug/kg and 3.9% at 124 ug/kg. Intermediate precision was estimated by testing 10 different samples (mussel and scallop) on three different days and ranged between 2.4 and 9.5%. The IC(50) values of the phosphatase used in this assay were determined for OA (1.2 nM), DTX-1 (1.6 nM) and DTX-2 (1.2 nM). The accuracy of the method was estimated by recovery testing for OA (mussel, 78-101%; king scallop, 98-114%), DTX-1 (king scallop, 79-102%) and DTX-2 (king scallop, 93%). Finally, the method was qualitatively compared to the mouse bioassay and LC-MS/MS. PMID- 22778905 TI - Dimethylarginine dimethylaminohydrolase/nitric oxide synthase pathway in liver and kidney: protective effect of cyanidin 3-O-beta-D-glucoside on ochratoxin-A toxicity. AB - The aim of the present study was to evaluate the effect of long-term cyanidin 3-O beta-D-glucoside (C3G) and/or Ochratoxin A (OTA)-exposure on dimethylarginine dimethylamino hydrolase/nitric oxide synthase (DDAH/NOS) pathway in rats. The experiments were performed in rats supplemented with C3G (1 g/kg feed), OTA (200 ppb), and OTA + C3G. After 4 weeks of daily treatment, liver and kidneys were processed for eNOS, iNOS and DDAH-1 Western blotting, nitrite levels evaluation and DDAH activity determination. Results show that OTA is able to induce iNOS both in kidney and liver, whereas OTA is able to induce eNOS and DDAH-1 overexpression and DDAH activation only in kidney, resulting in increased nitrite levels. In kidney of OTA + C3G fed rats, iNOS, eNOS and DDAH-1 expression were less pronounced compared with those observed in the OTA-treated group. Coherent with the decreased iNOS, eNOS and DDAH-1 expression a decrease in nitrite levels and DDAH activity was observed in the OTA + C3G group. Results demonstrate that C3G is able to counteract the deleterious effects of chronic consumption of OTA and also suggest a possible involvement of iNOS-eNOS-DDAH impairment in OTA nephrocarcinogenity. PMID- 22778906 TI - Control of ochratoxin A production in grapes. AB - Ochratoxin A (OTA) is a mycotoxin commonly present in cereals, grapes, coffee, spices, and cocoa. Even though the main objective of the food and feed chain processors and distributors is to avoid the extended contamination of plant derived foods and animal feeds with mycotoxins, until now, complete OTA removal from foods and feedstuffs is not feasible. Prevention through pre-harvest management is the best method for controlling mycotoxin contamination. However, in the case that the contamination occurs after this stage, the hazards associated with OTA must be managed through post-harvest strategies. Due to the increasing number of fungal strains resistant to chemical fungicides and the impact of these pesticides on the environment and human health, maximum levels of chemical residues have been regulated in many products. Alternative methods are necessary to substitute or complement treatments with fungicides to control fungi under field or storage conditions. Yeasts are considered one of the most potent biocontrol agents due to their biology and non-toxic properties. Epiphytic yeasts are the major component of the microbial community on the surface of grape berries and they are evolutionarily adapted to this ecological niche. Nowadays, several yeast species included in different genera are considered as potential biocontrol agents to control both, growth of ochratoxigenic Aspergillus species and OTA accumulation. PMID- 22778907 TI - Effects of two varieties of Bacillus thuringiensis maize on the biology of Plodia interpunctella. AB - On the market since 1996, genetically modified plants expressing an insecticidal toxin (Cry toxin stemmed from Bacillus thuringiensis) target several lepidopteran and coleopteran pests. In this study, we assessed the impact of two varieties of Bt maize producing different toxins (Cry1Ab or Cry1Fa, respectively) on the biology of a storage pest: Plodia interpunctella (Hubner) (Lepidoptera: Pyralidae). The Indianmeal moths were susceptible to both toxins but showed an escape behavior only from Cry1Fa. The weight of females issued from larvae reared on Cry1Ab increased with increasing toxin concentration, but adults of both sexes reared on Cry1Fa had decreased weight. Both toxins increased development time from egg to adult regardless of sex and had no impact on the male adult lifespan. Finally, we recorded a time lag between metamorphosis from the non-Bt and the Bt diets, which increased proportionally to Cry concentration in the Bt diet. PMID- 22778908 TI - The major histocompatibility complex in transplantation. AB - The transplant of organs is one of the greatest therapeutic achievements of the twentieth century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the principal target of the immune response is the MHC (major histocompatibility complex) molecules expressed on the surface of donor cells. However, we should not forget that the innate and adaptive immunities are closely interrelated and should be viewed as complementary and cooperating. When a human transplant is performed, HLA (human leukocyte antigens) molecules from a donor are recognized by the recipient's immune system triggering an alloimmune response Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. This paper will present MHC, the innate and adaptive immunities, and clinical HLA testing. PMID- 22778909 TI - Study of anterior chamber aqueous tube shunt by fourier-domain optical coherence tomography. AB - Purpose. This cross-sectional, observational study used Fourier-domain optical coherence tomography (OCT) to examine the position, patency, and the interior entrance site of anterior chamber (AC) aqueous tube shunts. Methods. The OCT, slitlamp biomicroscopy, and gonioscopy findings of 23 eyes of 18 patients with AC shunts were collected and compared. Results. OCT images demonstrated the shunt position and patency in all 23 eyes, and the details of the AC entrance in 16 eyes. The position of the tube varied, with the majority (14/23) on the surface of the iris. The exact position of the AC entrance relative to Schwalbe's line (SL) could be determined in 9 eyes (posterior to SL in 7 eyes, anterior in 2 eyes). At the AC entrance, growth of fibrous scar tissue was present between the tube and the corneal endothelium in all 16 eyes in which the entrance could be clearly visualized. It's a new finding that could not be visualized by slitlamp examination or lower resolution OCT. Conclusion. Compared to slitlamp examination, Fourier-domain OCT of AC tube shunts provided more detailed anatomic information regarding the insertion level relative to SL, scar tissue between the tube and the corneal endothelium, and patency of the tube opening. PMID- 22778910 TI - Expression Profiling of a Heterogeneous Population of ncRNAs Employing a Mixed DNA/LNA Microarray. AB - Mammalian transcriptomes mainly consist of non protein coding RNAs. These ncRNAs play various roles in all cells and are involved in multiple regulation pathways. More recently, ncRNAs have also been described as valuable diagnostic tools. While RNA-seq approaches progressively replace microarray-based technologies for high-throughput expression profiling, they are still not routinely used in diagnostic. Microarrays, on the other hand, are more widely used for diagnostic profiling, especially for very small ncRNA (e.g., miRNAs), employing locked nucleic acid (LNA) arrays. However, LNA microarrays are quite expensive for high throughput studies targeting longer ncRNAs, while DNA arrays do not provide satisfying results for the analysis of small RNAs. Here, we describe a mixed DNA/LNA microarray platform, where directly labeled small and longer ncRNAs are hybridized on LNA probes or custom DNA probes, respectively, enabling sensitive and specific analysis of a complex RNA population on a unique array in one single experiment. The DNA/LNA system, requiring relatively low amounts of total RNA, which complies with diagnostic references, was successfully applied to the analysis of differential ncRNA expression in mouse embryonic stem cells and adult brain cells. PMID- 22778912 TI - Hypertension in the high-cardiovascular-risk populations. PMID- 22778911 TI - Small RNA expression profiling by high-throughput sequencing: implications of enzymatic manipulation. AB - Eukaryotic regulatory small RNAs (sRNAs) play significant roles in many fundamental cellular processes. As such, they have emerged as useful biomarkers for diseases and cell differentiation states. sRNA-based biomarkers outperform traditional messenger RNA-based biomarkers by testing fewer targets with greater accuracy and providing earlier detection for disease states. Therefore, expression profiling of sRNAs is fundamentally important to further advance the understanding of biological processes, as well as diagnosis and treatment of diseases. High-throughput sequencing (HTS) is a powerful approach for both sRNA discovery and expression profiling. Here, we discuss the general considerations for sRNA-based HTS profiling methods from RNA preparation to sequencing library construction, with a focus on the causes of systematic error. By examining the enzymatic manipulation steps of sRNA expression profiling, this paper aims to demystify current HTS-based sRNA profiling approaches and to aid researchers in the informed design and interpretation of profiling experiments. PMID- 22778913 TI - Hypertension-related admissions and outcome in a tertiary hospital in northeast Nigeria. AB - Cardiovascular disease has reached near epidemic proportion in sub-Saharan Africa, and systemic hypertension (SH) remains the driver of cardiovascular complications. We studied hypertension-related admissions and their outcome at the Abubaker Tafawa Balewa University Teaching Hospital (ATBUTH) Bauchi, Northeast Nigeria. Records of all patients admitted into the medical wards between 1st November 2010 and 31st October 2011 were studied, and case files of those managed for SH complications were selected for detailed examination. Of the total 3108 admissions, 735 (23.7%) were hypertension related. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 167.4 +/- 18.2 and 98.6 +/ 13.5, respectively, at presentation. Although, hypertension-related admissions were 23.7% of total admissions, there was an excess of mortality associated with SH complications (42.9%). Stroke was the commonest, and it accounted for 44.4% of cases. Stroke had the highest mortality (39.3%), followed by chronic kidney disease (36.6%); hypertensive emergencies (30.9%) and hypertensive heart failure had the lowest intrahospital mortality (27.5%). In conclusion, SH-related admissions are common among medical admissions in Bauchi Nigeria and are associated with high mortality. Community interventions that promote early diagnosis and reduction of cardiovascular risk profiles are urgently needed to reduce SH deaths. PMID- 22778914 TI - Situational motivation and perceived intensity: their interaction in predicting changes in positive affect from physical activity. AB - There is evidence that affective experiences surrounding physical activity can contribute to the proper self-regulation of an active lifestyle. Motivation toward physical activity, as portrayed by self-determination theory, has been linked to positive affect, as has the intensity of physical activity, especially of a preferred nature. The purpose of this experimental study was to examine the interaction between situational motivation and intensity [i.e., ratings of perceived exertion (RPE)] in predicting changes in positive affect following an acute bout of preferred physical activity, namely, running. Fourty-one female runners engaged in a 30-minute self-paced treadmill run in a laboratory context. Situational motivation for running, pre- and post-running positive affect, and RPE were assessed via validated self-report questionnaires. Hierarchical regression analyses revealed a significant interaction effect between RPE and introjection (P < .05) but not between RPE and identified regulation or intrinsic motivation. At low levels of introjection, the influence of RPE on the change in positive affect was considerable, with higher RPE ratings being associated with greater increases in positive affect. The implications of the findings in light of SDT principles as well as the potential contingencies between the regulations and RPE in predicting positive affect among women are discussed. PMID- 22778915 TI - Mental health, wellness, and childhood overweight/obesity. AB - Childhood obesity is a growing concern, and while progress has been made to understand the association between multiple biological factors (i.e., genetics, nutrition, exercise etc.), little is known about the relationship between mental health and childhood obesity. In this paper, we offer a review of current evidence about the association between mental health and childhood obesity. A systematic literature search of peer-reviewed, English-language studies published between January 2000 and January 2011 was undertaken and resulted in 759 unique records, of which 345 full-text articles were retrieved and 131 articles were included. A theoretical model is proposed to organize the paper and reflect the current state of the literature and includes psychological factors (i.e., depression and anxiety, self-esteem, body dissatisfaction, eating disordered symptoms, and emotional problems); psychosocial mediating variables (i.e., weight based teasing and concern about weight and shape), and wellness factors (i.e., quality of life and resiliency/protective factors). We conclude with a number of recommendations to support the creation of solutions to the rise in childhood obesity rates that do not further marginalize overweight and obese children and youth and that can potentially improve the well-being of all children and youth regardless of their weight status. PMID- 22778916 TI - Choline Deficiency Attenuates Body Weight Gain and Improves Glucose Tolerance in ob/ob Mice. AB - Previous studies demonstrated that choline supply is directly linked to high-fat diet-induced obesity and insulin resistance in mice. The aim of this study was to evaluate if choline supply could also modulate obesity and insulin resistance caused by a genetic defect. Eight-week-old male ob/ob mice were fed for two months with either choline-deficient or choline-supplemented diet. Tissue weight including fat mass and lean mass was assessed. Intracellular signaling, plasma glucagon and insulin, and glucose and insulin tolerance tests were also investigated. The choline-deficient diet slowed body weight gain and decreased fat mass. Choline deficiency also decreased plasma glucose level and improved glucose and insulin tolerance although fatty liver was exacerbated. Increased adipose lipolytic activity, decreased plasma glucagon and reduced expression of hepatic glucagon receptor were also observed with the choline-deficient diet. Our results demonstrate that a choline-deficient diet can decrease fat mass and improve glucose tolerance in obese and diabetic mice caused by a genetic defect. PMID- 22778917 TI - Binge Eating Disorder Mediates Links between Symptoms of Depression, Anxiety, and Caloric Intake in Overweight and Obese Women. AB - Despite considerable comorbidity between mood disorders, binge eating disorder (BED), and obesity, the underlying mechanisms remain unresolved. Therefore, the purpose of this study was to examine models by which internalizing behaviors of depression and anxiety influence food intake in overweight/obese women. Thirty two women (15 BED, 17 controls) participated in a laboratory eating-episode and completed questionnaires assessing symptoms of anxiety and depression. Path analysis was used to test mediation and moderation models to determine the mechanisms by which internalizing symptoms influenced kilocalorie (kcal) intake. The BED group endorsed significantly more symptoms of depression (10.1 versus 4.8, P = 0.005 ) and anxiety (8.5 versus 2.7, P = 0.003). Linear regression indicated that BED diagnosis and internalizing symptoms accounted for 30% of the variance in kcal intake. Results from path analysis suggested that BED mediates the influence of internalizing symptoms on total kcal intake (empirical P < 0.001 ). The associations between internalizing symptoms and food intake are best described as operating indirectly through a BED diagnosis. This suggests that symptoms of depression and anxiety influence whether one engages in binge eating, which influences kcal intake. Greater understanding of the mechanisms underlying the associations between mood, binge eating, and food intake will facilitate the development of more effective prevention and treatment strategies for both BED and obesity. PMID- 22778918 TI - Physical activity behaviour: an overview of current and emergent theoretical practices. AB - Physical activity research has been dominated by traditional cognitive rationale paradigms utilized within other domains. Though this approach to physical activity behavior has greatly enhanced our understanding of the key determinants, it has done little to eradicate the health problems we currently face. In order to achieve lasting change though, multilevel interventions may prove effective. Ecological perspectives have been proposed as an effective approach in combating current physical inactivity levels. Nevertheless, this approach is in its infancy and much has still to be learned. The aim of this paper is to provide an overview of the main behavioral models used within the physical activity domain while proposing the need for further models that will embrace the principles presented by ecological and complexity theories. PMID- 22778919 TI - Weight Gain Prevention for College Freshmen: Comparing Two Social Cognitive Theory-Based Interventions with and without Explicit Self-Regulation Training. AB - The college transition represents a critical period for maintaining a healthy weight, yet intervention participation and retention represent significant challenges. The objective of this investigation was to evaluate the preliminary efficacy and acceptability of two interventions to prevent freshman weight gain. One intervention provided opportunities to improve outcome expectations and self efficacy within a social cognitive theory framework (SCT), while the other targeted the same variables but focused on explicit training in self-regulation skills (SCTSR). Methods. Freshmen (n = 45) aged >18 years were randomized to a 14 week intervention, SCT or SCTSR; both included online modules and in-class meetings. Of the 45 students randomized, 5 withdrew before the classes began and 39 completed pre- and posttesting. Primary outcomes included body weight/composition, health behaviors, and program acceptability. Analyses included independent sample t-tests, repeated measures ANOVA, and bivariate correlational analyses. Results. Body weight increased over the 14-week period, but there was no group difference. Percent body fat increased in SCTSR but not SCT (mean difference: SCTSR, +1.63 +/- 0.52%; SCT, -0.25 +/- 0.45%; P = 0.01). Class attendance was 100% (SCTSR) and 98% (SCT); SCTSR students (>50%) remarked that the online tracking required "too much time." Conclusions. The intervention was well received, although there were no improvements in weight outcomes. PMID- 22778920 TI - Comparing years of healthy life, measured in 16 ways, for normal weight and overweight older adults. AB - Introduction. The traditional definitions of overweight and obesity are not age specific, even though the relationship of weight to mortality is different for older adults. Effects of adiposity on aspects of health beside mortality have not been well investigated. Methods. We calculated the number of years of healthy life (YHL) in the 10 years after baseline, for 5,747 older adults. YHL was defined in 16 different ways. We compared Normal and Overweight persons, classified either by body mass index (BMI) or by waist circumference (WC). Findings. YHL for Normal and Overweight persons differed significantly in 25% of the comparisons, of which half favored the Overweight. Measures of physical health favored Normal weight, while measures of mental health and quality of life favored Overweight. Overweight was less favorable when defined by WC than by BMI. Obese persons usually had worse outcomes. Discussion. Overweight older adults averaged as many years of life and years of healthy life as those of Normal weight. There may be no outcome based reason to distinguish Normal from Overweight for older adults. Conclusion. The "Overweight paradox" appears to hold for nonmortality outcomes. New adiposity standards are needed for older adults, possibly different by race and sex. PMID- 22778921 TI - Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes. AB - Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter. AICAR is an intermediate in the purine de novo synthesis, and its tissue concentrations can be increased, in vivo, by low doses of methotrexate (MTX) through the inhibition of the enzyme AICAR transformylase. We report here the first evidence that, in experimental type 2 diabetes, chronic treatment with low doses of MTX increases skeletal muscle GLUT4 expression and improves metabolic control. MTX (0.5 mg/kg body weight) or vehicle was administered intraperitoneally, once a week for 4 weeks, to genetically diabetic female C57BL/KsJ-m(+)/(+)Lept(db) mice (db(+)/db(+)) and their normoglycemic littermates (db(+)/(+)m). In the db(+)/db(+) mice, MTX treatment was associated with a ~2-fold increase in skeletal muscle GLUT4 protein concentration and a >4-fold increase in GLUT4 mRNA expression (P < 0.01, all), as compared to vehicle-treated mice; no significant differences were noted in controls. MTX treatment was also associated with a significant reduction of glucose and insulin serum concentrations in diabetic mice (P < 0.001), and glucose levels only (P < 0.05) in controls. These data indicate a different route to increase skeletal muscle GLUT4 expression, through the potential inhibition of the enzyme AICAR transformylase. PMID- 22778922 TI - Metabolic syndrome: epidemiology, pathophysiology, and nutrition intervention. PMID- 22778923 TI - A Qualitative Exploration of the Economic and Social Effects of Microcredit among People Living with HIV/AIDS in Uganda. AB - HIV medical care, including antiretroviral therapy (ART), is often successful in restoring physical health and functioning. But in developing countries, HIV medical care is often insufficient to achieve social and economic health, and hence innovative economic support programs are much needed. We conducted semistructured interviews with 30 adults receiving ART and microcredit loans operated by Uganda Cares. Using content analysis, we explored the impact of the microcredit loans on the economic, social, and psychological well-being of respondents. Most respondents indicated that the microcredit loans played a positive role in their lives, helped them to keep their children in school and sustain their families, and improved their self-esteem and status in the community. In addition, we also found significant positive knowledge spill-over and network effects in the program with regard to business management and support. However, more than half of the participants indicated experiencing repayment problems either personally or with other group members due to unexpected emergencies and sickness. These findings highlight that microcredit programs have the potential of being an economic support system for HIV clients trying to reestablish their livelihoods, especially in resource-constrained settings, though more research is needed to determine the overall economic viability of such programs. PMID- 22778924 TI - Adolescents Living with HIV: An Indian Profile. AB - Purpose. Although there have been studies on the presence of Human Immunodeficiency Virus (HIV) among the adult and even pediatric population, the adolescent population has been neglected. The main objective of this study was to understand and describe the profile of adolescents accessing the Integrated Counseling and Testing Centre (ICTC) at a tertiary healthcare centre in north India. This was a retrospective analysis of the data collected where, in addition to the analysis of the presence of HIV among the target population, a comparative analysis of HIV-positive and negative individuals was also carried out. Methods. Counselors at the ICTC of All India Institute of Medical Sciences recorded responses of the patients, and pre- and posttest counseling was performed appropriately. Also, HIV testing was performed using rapid tests (EIA) and ELISA. Both pre- and posttest counseling was performed for most of the patients. Also, the data collected from 2005 to May, 2011 was then retrospectively analyzed using various statistical tests, such as, Chi-square test and odds ratios. Results. Out of 979, 84 tested HIV positive. Discrimination at multiple levels was observed.The 10-14 years age group was 0.56 times more likely to be HIV positive than 15-19 year old. HIV serostatus was strongly associated with risk behavior (P = 0.003) with heterosexual transmission being the most common. Conclusion. These findings highlight the profile of adolescents in India and their equation with HIV on demographic and psychosocial levels. PMID- 22778925 TI - Induction of Fetal Hemoglobin In Vivo Mediated by a Synthetic gamma-Globin Zinc Finger Activator. AB - Sickle cell disease (SCD) and beta-thalassemia patients are phenotypically normal if they carry compensatory hereditary persistence of fetal hemoglobin (HPFH) mutations that result in increased levels of fetal hemoglobin (HbF, gamma-globin chains) in adulthood. Thus, research has focused on manipulating the reactivation of gamma-globin gene expression during adult definitive erythropoiesis as the most promising therapy to treat these hemoglobinopathies. Artificial transcription factors (ATFs) are synthetic proteins designed to bind at a specific DNA sequence and modulate gene expression. The artificial zinc finger gg1-VP64 was designed to target the -117 region of the (A)gamma-globin gene proximal promoter and activate expression of this gene. Previous studies demonstrated that HbF levels were increased in murine chemical inducer of dimerization (CID)-dependent bone marrow cells carrying a human beta-globin locus yeast artificial chromosome (beta-YAC) transgene and in CD34(+) erythroid progenitor cells from normal donors and beta-thalassemia patients. Herein, we report that gg1-VP64 increased gamma-globin gene expression in vivo, in peripheral blood samples from gg1-VP64 beta-YAC double-transgenic (bigenic) mice. Our results demonstrate that ATFs function in an animal model to increase gene expression. Thus, this class of reagent may be an effective gene therapy for treatment of some inherited diseases. PMID- 22778926 TI - Spatiotemporal dysfunction of the vascular permeability barrier in transgenic mice with sickle cell disease. AB - Sickle cell disease (SCD) is characterized by chronic intravascular hemolysis that generates excess cell-free hemoglobin in the blood circulation. Hemoglobin causes multiple endothelial dysfunctions including increased vascular permeability, impaired reactivity to vasoactive agonists, and increased adhesion of leukocytes to the endothelium. While the adhesive and vasomotor defects of SCD associated with cell-free hemoglobin are well defined, the vascular permeability phenotype remains poorly appreciated. We addressed this issue in two widely used and clinically relevant mouse models of SCD. We discovered that the endothelial barrier is normal in most organs in the young but deteriorates with aging particularly in the lung. Indeed, middle-aged sickle mice developed pulmonary edema revealing for the first time similarities in the chronic permeability phenotypes of the lung in mice and humans with SCD. Intravenous administration of lysed red blood cells into the circulation of sickle mice increased vascular permeability significantly in the lung without impacting permeability in other organs. Thus, increased vascular permeability is an endothelial dysfunction of SCD with the barrier in the lung likely the most vulnerable to acute inflammation. PMID- 22778928 TI - Metabolic risk factors, leisure time physical activity, and nutrition in german children and adolescents. AB - Purpose. We assessed the five components of the metabolic syndrome (MetS) as defined by the International Diabetes Federation (IDF) in 6040 (3158 males) youths aged 6-16 years who participated in the Praventions-Erziehungs-Programm (PEP Family Heart Study) in Nuernberg between 2000 and 2007. The purpose of this cross-sectional study was to examine associations with lifestyle habits. Results and Discussion. The prevalence of MetS was low in children (1.6%) and adolescents (2.3%). High waist circumference (WC) and low HDL-C were slightly higher in females (9.5% and 7.5%, resp.) than in males (8.8% and 5.7%, resp.). Low leisure time physical activity (LTPA) was significantly associated with low HDL-C (odds ratio [OR] 2.4; 95% CI 1.2-5.0) and inversely associated with hypertension (r = 0.146), hypertriglyceridemia (r = -0.141), and central adiposity (r = -0.258). The risk for low HDL-C (<=1.3 mmol/L) was 1.7-fold (CI 1.0-2.6) higher in youth with high (>=33%) saturated fat consumption. A low polyunsaturated/saturated fat ratio (P/S ratio) was significantly associated with fasting hyperglycemia (OR 1.4; 95% CI 1.0-1.2). PMID- 22778927 TI - Diagnosis of Fanconi Anemia: Mutation Analysis by Multiplex Ligation-Dependent Probe Amplification and PCR-Based Sanger Sequencing. AB - Fanconi anemia (FA) is a rare inherited disease characterized by developmental defects, short stature, bone marrow failure, and a high risk of malignancies. FA is heterogeneous: 15 genetic subtypes have been distinguished so far. A clinical diagnosis of FA needs to be confirmed by testing cells for sensitivity to cross linking agents in a chromosomal breakage test. As a second step, DNA testing can be employed to elucidate the genetic subtype of the patient and to identify the familial mutations. This knowledge allows preimplantation genetic diagnosis (PGD) and enables prenatal DNA testing in future pregnancies. Although simultaneous testing of all FA genes by next generation sequencing will be possible in the near future, this technique will not be available immediately for all laboratories. In addition, in populations with strong founder mutations, a limited test using Sanger sequencing and MLPA will be a cost-effective alternative. We describe a strategy and optimized conditions for the screening of FANCA, FANCB, FANCC, FANCE, FANCF, and FANCG and present the results obtained in a cohort of 54 patients referred to our diagnostic service since 2008. In addition, the follow up with respect to genetic counseling and carrier screening in the families is discussed. PMID- 22778929 TI - Goal-directed fluid therapy using stroke volume variation does not result in pulmonary fluid overload in thoracic surgery requiring one-lung ventilation. AB - Background. Goal-directed fluid therapy (GDT) guided by functional parameters of preload, such as stroke volume variation (SVV), seems to optimize hemodynamics and possibly improves clinical outcome. However, this strategy is believed to be rather fluid aggressive, and, furthermore, during surgery requiring thoracotomy, the ability of SVV to predict volume responsiveness has raised some controversy. So far it is not known whether GDT is associated with pulmonary fluid overload and a deleterious reduction in pulmonary function in thoracic surgery requiring one-lung-ventilation (OLV). Therefore, we assessed the perioperative course of extravascular lung water index (EVLWI) and p(a)O(2)/F(i)O(2)-ratio during and after thoracic surgery requiring lateral thoracotomy and OLV to evaluate the hypothesis that fluid therapy guided by SVV results in pulmonary fluid overload. Methods. A total of 27 patients (group T) were enrolled in this prospective study with 11 patients undergoing lung surgery (group L) and 16 patients undergoing esophagectomy (group E). Goal-directed fluid management was guided by SVV (SVV < 10%). Measurements were performed directly after induction of anesthesia (baseline-BL), 15 minutes after implementation OLV (OLVimpl15), and 15 minutes after termination of OLV (OLVterm15). In addition, postoperative measurements were performed at 6 (6postop), 12 (12postop), and 24 (24postop) hours after surgery. EVLWI was measured at all predefined steps. The p(a)O(2)/F(i)O(2)-ratio was determined at each point during mechanical ventilation (group L: BL OLVterm15; group E: BL-24postop). Results. In all patients (group T), there was no significant change (P > 0.05) in EVLWI during the observation period (BL: 7.8 +/- 2.5, 24postop: 8.1 +/- 2.4 mL/kg). A subgroup analysis for group L and group E also did not reveal significant changes of EVLWI. The p(a)O(2)/F(i)O(2)-ratio decreased significantly during the observation period (group L: BL: 462 +/- 140, OLVterm15: 338 +/- 112 mmHg; group E: BL: 389 +/- 101, 24postop: 303 +/- 74 mmHg) but remained >300 mmHg except during OLV. Conclusions. SVV-guided fluid management in thoracic surgery requiring lateral thoracotomy and one-lung ventilation does not result in pulmonary fluid overload. Although oxygenation was reduced, pulmonary function remained within a clinically acceptable range. PMID- 22778930 TI - Managing Mental Health Disorders Resulting from Trauma through Yoga: A Review. AB - There are many and varied types of trauma. The extent to which trauma influences the mental health of an individual depends on the nature of trauma, as well as on the individual's coping capabilities. Often trauma is followed by depression, anxiety, and PTSD. As the pharmacological remedies for these conditions often have undesirable side-effects, nonpharmacological remedies are thought of as a possible add-on treatment. Yoga is one such mind-body intervention. This paper covers eleven studies indexed in PubMed, in which mental health disorders resulting from trauma were managed through yoga including meditation. The aim was to evaluate the use of yoga in managing trauma-related depression, anxiety, PTSD and physiological stress following exposure to natural calamities, war, interpersonal violence, and incarceration in a correctional facility. An attempt has also been made to explore possible mechanisms underlying benefits seen. As most of these studies were not done on persons exposed to trauma that had practiced yoga, this is a definite area for further research. PMID- 22778931 TI - Influence of spirituality on depression, posttraumatic stress disorder, and suicidality in active duty military personnel. AB - Understanding the role of spirituality as a potential coping mechanism for military personnel is important given growing concern about the mental health issues of personnel returning from war. This study seeks to determine the extent to which spirituality is associated with selected mental health problems among active duty military personnel and whether it moderates the relationship between combat exposure/deployment and (a) depression, (b) posttraumatic stress disorder (PTSD), and (c) suicidality in active duty military personnel. Data were drawn from the 2008 Department of Defense Survey of Health Related Behaviors Among Active Duty Military Personnel. Over 24,000 randomly selected active duty personnel worldwide completed an anonymous self-report questionnaire. High spirituality had a significant protective effect only for depression symptoms. Medium, as opposed to high or low, levels of spirituality buffered each of the mental health outcomes to some degree. Medium and low spirituality levels predicted depression symptoms but only among those with moderate combat exposure. Medium spirituality levels also predicted PTSD symptoms among those with moderate levels of combat exposure and predicted self-reported suicidal ideation/attempt among those never deployed. These results point to the complex relationship between spirituality and mental health, particularly among military personnel and the need for further research. PMID- 22778933 TI - A pilot survey of clergy regarding mental health care for children. AB - Collaborations between healthcare and faith-based organizations have emerged in the drive to improve access to care. Little research has examined clergy views on collaborations in the provision of mental healthcare, particularly to children. The current paper reports survey responses of 25 clergy from diverse religious traditions concerning mental health care in children. Subjects queried include clergy referral habits, specific knowledge of childhood conditions such as depression and anxiety, past experiences with behavioral health workers, and resources available through their home institutions. Overall, surveyed clergy support collaborations to improve childhood mental health. However, they vary considerably in their confidence with recognizing mental illness in children and perceive significant barriers to collaborating with mental health providers. PMID- 22778932 TI - Religious versus Conventional Psychotherapy for Major Depression in Patients with Chronic Medical Illness: Rationale, Methods, and Preliminary Results. AB - This paper (1) reviews the physical and religious barriers to CBT that disabled medically ill-depressed patients face, (2) discusses research on the relationship between religion and depression-induced physiological changes, (3) describes an ongoing randomized clinical trial of religious versus secular CBT in chronically ill patients with mild-to-moderate major depression designed to (a) overcome physical and religious barriers to CBT and (b) compare the efficacy of religious versus secular CBT in relieving depression and improving immune and endocrine functions, and (4) presents preliminary results that illustrate the technical difficulties that have been encountered in implementing this trial. CBT is being delivered remotely via instant messaging, telephone, or Skype, and Christian, Jewish, Muslim, Buddhist, and Hindu versions of religious CBT are being developed. The preliminary results described here are particular to the technologies employed in this study and are not results from the CBT clinical trial whose findings will be published in the future after the study ends and data are analyzed. The ultimate goal is to determine if a psychotherapy delivered remotely that integrates patients' religious resources improves depression more quickly than a therapy that ignores them, and whether religious CBT is more effective than conventional CBT in reversing depression-induced physiological changes. PMID- 22778934 TI - Management of rectal cancer and liver metastatic disease: which comes first? AB - In the last few decades there have been significant changes in the approach to rectal cancer management. A multimodality approach and advanced surgical techniques have led to an expansion of the treatment of metastatic disease, with improved survival. Hepatic metastases are present at one point or another in about 50% of patients with colorectal cancer, with surgical resection being the only chance for cure. As the use of multimodality treatment has allowed the tackling of more complicated cases, one of the main questions that remain unanswered is the management of patients with synchronous rectal cancer and hepatic metastatic lesions. The question is one of priority, with all possible options being explored. Specifically, these include the simultaneous rectal cancer and hepatic metastases resection, the rectal cancer followed by chemotherapy and then by the liver resection, and finally the "liver-first" option. This paper will review the three treatment options and attempt to dissect the indications for each. In addition, the role of laparoscopy in the synchronous resection of rectal cancer and hepatic metastases will be reviewed in order to identify future trends. PMID- 22778935 TI - Intersphincteric resection for low rectal cancer: an overview. AB - The treatment of rectal cancer has evolved from being solely a surgical endeavor to a multidisciplinary practice. Despite the improvement in outcomes conferred by the addition of chemoradiation therapy to rectal cancer treatment, advances in surgical technique have significantly increased rates of sphincter preservation and the avoidance of a permanent stoma. In recent years, intersphincteric resection for low rectal cancer has been offered and performed in patients as an alternative to abdominoperineal resection. An overview of this procedure, including indications, oncological and functional results based on current literature, is presented herein. PMID- 22778936 TI - Is there a role for neoadjuvant targeted therapy to downsize primary tumors for organ sparing strategies in renal cell carcinoma? AB - With an increasing number of small renal masses being diagnosed organ-preserving treatment strategies such as nephron-sparing surgery (NSS) or radiofrequency and cryoablation are gaining importance. There is evidence that preserving renal function reduces the risk of death of any cause, cardiovascular events, and hospitalization. Some patients have unfavourable tumor locations or large tumors unsuitable for NSS or ablation which is a clinical problem especially in those with imperative indications to preserve renal function. These patients may benefit from downsizing primary tumors by targeted therapy. This paper provides an overview of the current evidence, safety, controversies, and ongoing trials. PMID- 22778937 TI - Survival Benefit of Adjuvant Radiation Therapy for Gastric Cancer following Gastrectomy and Extended Lymphadenectomy. AB - Purpose. Although randomized trials suggest a survival benefit of adjuvant chemotherapy and radiation therapy (XRT) for gastric adenocarcinoma, its use in patients who undergo an extended lymphadenectomy is less clear. The purpose of this study was to determine if a survival benefit exists in gastric cancer patients who receive adjuvant XRT following resection with extended lymphadenectomy. Methods. The SEER registry was queried for records of patients with resected gastric adenocarcinoma from 1988 to 2007. Multivariable Cox regression models were used to assess independent prognostic factors affecting overall survival (OS) and disease-specific survival (DSS). Results. Of 15,060 patients identified, 3,208 (21%) received adjuvant XRT. Adjuvant XRT was independently associated with improved OS (HR 0.67, CI 0.64-0.71) and DSS (HR 0.69, CI 0.65-0.73) in stages IB through IV (M0). This OS and DSS benefit persisted regardless of the extent of lymphadenectomy. Furthermore, lymphadenectomy with >25 LN resected was associated with improved OS and DSS compared with <15 LN or 15-25 LN. Conclusion. This population-based study shows a survival benefit of adjuvant XRT following gastrectomy that persists in patients who have an extended lymphadenectomy. Furthermore, removal of >25 LNs results in improved OS and DSS compared with patients who have fewer LNs resected. PMID- 22778938 TI - Surgical treatment of peritoneal carcinomatosis from gastric cancer. AB - Peritoneal carcinomatosis from gastric cancer is considered a fatal disease with limited treatment options. Recent advances in the understanding of the disease process, systemic chemotherapy, and application of cytoreductive surgery and hyperthermic chemoperfusion have shown promising results in the management of this difficult disease. Novel therapies such as extensive intraperitoneal lavage and intraperitoneal targeted agents are being applied in the management of this disease. We review the current literature in this field and describe the rationale behind some of these advances. PMID- 22778939 TI - Is there a role for postmastectomy radiation therapy in ductal carcinoma in situ? AB - Background. DCIS treated by mastectomy ensures high local control rates. There is limited data on risk for relapse and lack of clear indication for adjuvant radiation therapy (RT). We report a retrospective review on a population of DCIS patients treated with mastectomy. The objective was to identify the overall incidence of relapse, risk factors for local recurrence, and accordingly for whom adjuvant postmastectomy RT may be considered. Methods. This is an IRB-approved retrospective study on a prospective breast cancer database. From 1997 to 2007, we identified 969 patients with diagnoses of DCIS, among them 211 breasts in 207 patients were treated with mastectomy and comprise the study group. Results. With a median followup of 55 months (4.6 years) the 10-year relapse-free survival is 97%. Two of 211 breasts (0.9%) treated with mastectomy developed a local-regional recurrence. Both the relapses were among patients defined as having <1 mm final mastectomy margin. Conclusions. The rare local relapse after mastectomy limits our ability to reliably identify risk factors for relapse. The consideration for postmastectomy RT should be based on an individualized risk evaluating surgical technique used, presence of BRCA mutation, grade and extent of tumor, and proximity of lesion to the margin of resection. PMID- 22778940 TI - Analysis of risk factors for lymph nodal involvement in early stages of rectal cancer: when can local excision be considered an appropriate treatment? Systematic review and meta-analysis of the literature. AB - Background. Over the past ten years oncological outcomes achieved by local excision techniques (LETs) as the sole treatment for early stages of rectal cancer (ESRC) have been often disappointing. The reasons for these poor results lie mostly in the high risk of the disease's diffusion to local-regional lymph nodes even in ESRC. Aims. This study aims to find the correct indications for LET in ESRC taking into consideration clinical-pathological features of tumours that may reduce the risk of lymph node metastasis to zero. Methods. Systematic literature review and meta-analysis of casistics of ESRC treated with total mesorectal excision with the aim of identifying risk factors for nodal involvement. Results. The risk of lymph node metastasis is higher in G >= 2 and T >= 2 tumours with lymphatic and/or vascular invasion. Other features which have not yet been sufficiently investigated include female gender, TSM stage >1, presence of tumour budding and/or perineural invasion. Conclusions. Results comparable to radical surgery can be achieved by LET only in patients with T(1) N(0) G(1) tumours with low-risk histological features, whereas deeper or more aggressive tumours should be addressed by radical surgery (RS). PMID- 22778941 TI - Mechanisms of Cisplatin-Induced Apoptosis and of Cisplatin Sensitivity: Potential of BIN1 to Act as a Potent Predictor of Cisplatin Sensitivity in Gastric Cancer Treatment. AB - Cisplatin is the most important and efficacious chemotherapeutic agent for the treatment of advanced gastric cancer. Cisplatin forms inter- and intrastrand crosslinked DNA adducts and its cytotoxicity is mediated by propagation of DNA damage recognition signals to downstream pathways involving ATR, p53, p73, and mitogen-activated protein kinases, ultimately resulting in apoptosis. Cisplatin resistance arises through a multifactorial mechanism involving reduced drug uptake, increased drug inactivation, increased DNA damage repair, and inhibition of transmission of DNA damage recognition signals to the apoptotic pathway. In addition, a new mechanism has recently been revealed, in which the oncoprotein c Myc suppresses bridging integrator 1 (BIN1), thereby releasing poly(ADP ribose)polymerase 1, which results in increased DNA repair activity and allows cancer cells to acquire cisplatin resistance. The present paper focuses on the molecular mechanisms of cisplatin-induced apoptosis and of cisplatin resistance, in particular on the involvement of BIN1 in the maintenance of cisplatin sensitivity. PMID- 22778942 TI - Immunohistochemical biomarkers in gastric cancer research and management. AB - Gastric cancer still represents a major health problem, despite a decrease in its incidence in the last years. Due to the social impact of gastric cancer (GC), there is a need for novel biomarkers in order to stratify patients into appropriate screening, surveillance, or treatment programs. Although histopathology remains the most reliable and less expensive method, numerous efforts have been made searching for novel biomarkers. In recent years, several molecules have been identified and tested for their clinical relevance in GC management. In this paper, we will focus on a well-known GC marker, whose determination is mandatory in GC, HER2, a marker whose correlation with prognosis is still controversial (VEGF-A) and a quite novel, unconventional marker, the ether-a-go-go-related gene 1 (hERG1). All these proteins can be easily detected with immunohistochemistry, a technique widely used both in diagnostic and research laboratories that represents a link between surgical and molecular pathology, basic science, and clinical medicine. PMID- 22778943 TI - Preceptorship and affirmation in the intergenerational world of nursing practice. AB - Research has shown that while preceptorship offers a reality-oriented learning environment and facilitates competence of students, there are inherent rewards and stressors associated with the experience. Students and preceptors can be from different generations, and as such, they may often come to the learning space with differing values and expectations. The nature of the preceptorship experience in this intergenerational context was explored in a recent phenomenological study with seven preceptors and seven nursing students in an undergraduate nursing program in Eastern Canada. Overall the experience was found to be inclusive of three main themes: being affirmed, being challenged, and being on a pedagogical journey. In this paper we explore the first of these themes, being affirmed. Highlighting the positive aspects of the preceptorship experience in the intergenerational context is necessary to promote a culture of openness and respect for generational differences within clinical nursing practice settings and to improving the overall quality of the educational experience. PMID- 22778944 TI - Advanced nursing directives: integrating validated clinical scoring systems into nursing care in the pediatric emergency department. AB - In an effort to improve the quality and flow of care provided to children presenting to the emergency department the implementation of nurse-initiated protocols is on the rise. We review the current literature on nurse-initiated protocols, validated emergency department clinical scoring systems, and the merging of the two to create Advanced Nursing Directives (ANDs). The process of developing a clinical pathway for children presenting to our pediatric emergency department (PED) with suspected appendicitis will be used to demonstrate the successful integration of validated clinical scoring systems into practice through the use of Advanced Nursing Directives. Finally, examples of 2 other Advanced Nursing Directives for common clinical PED presentations will be provided. PMID- 22778945 TI - Single-port laparoscopic surgery in children: concept and controversies of the new technique. AB - Single-incision laparoscopic surgery (SILS) is emerging as an alternative technique to conventional laparoscopy for the treatment of common surgical diseases. Despite its wide use, the adoption of SILS in children has been slower since the broad application of minimally invasive techniques in children, in general, has historically lagged behind those in adults. This paper reviews the evolution of SILS from its original conception and its application in the field of pediatric surgery. PMID- 22778946 TI - Correlates of Delayed Diagnosis among Human Immunodeficiency Virus-Infected Pulmonary Tuberculosis Suspects in a Rural HIV Clinic, South Africa. AB - Background. Delay in pulmonary tuberculosis (PTB) diagnosis is one of the major factors that affect outcome and threatens continued spread of tuberculosis. This study aimed at determining factors associated with delayed PTB diagnosis among human immunodeficiency virus (HIV) infected individuals. Methods. A retrospective observational study was done using clinic records of HIV-infected PTB suspects attending an HIV/AIDS clinic at Tintswalo rural hospital in South Africa (SA) between January 2006 and December 2007. Using routine clinic registers, 480 records were identified. Results. PTB diagnosis delay was found among 77/176 (43.8%) of the patients diagnosed with PTB. The mean delay of PTB diagnosis was 170.6 days; diagnosis delay ranged 1-30 days in 27 (35.1%) patients, 31-180 days in 24 (33.8%) patients; 24 (31.2%) patients remained undiagnosed for >=180 days. Independent factors associated with delayed diagnosis were: older age >40 years (Odds Ratio (OR) 3.43, 95% CI 1.45-8.08) and virological failure (OR 2.72, 95% CI 1.09-6.74). Conclusion. There is a considerable delayed PTB diagnosis among HIV infected patients in rural SA. Older patients as well as patients with high viral load are at a higher risk of PTB diagnosis delay. Therefore efforts to reduce PTB diagnosis delay need to emphasised. PMID- 22778947 TI - Beyond Genetics in Glioma Pathways: The Ever-Increasing Crosstalk between Epigenomic and Genomic Events. AB - Diffuse gliomas are the most frequent brain tumor in adults. This group of brain neoplasms, ranging from histologically benign to aggressive malignant forms, represents a challenge in modern neurooncology because of the diffuse infiltrative growth pattern and the inherent tendency to relapse as a more malignant tumor. Once the disease achieves the stage of glioblastoma multiforme (GBM), the prognosis of patients is dismal and the median survival time is 15 months. Exhaustive genetic analyses have revealed a variety of deregulated genetic pathways involved in DNA repair, apoptosis, cell migration/adhesion, and cell cycle. Recently, investigation of epigenetic alterations in gliomas has contributed to depict the complexity of the molecular lesions leading to these malignancies. Even though, the efficacy of the state-of-the-art form of chemotherapy in malignant gliomas with temozolomide is based on the methylation associated silencing of the DNA repair gene MGMT. Nevertheless, the whole scenario including global DNA hypomethylation, aberrant promoter hypermethylation, histone modification, chromatin states, and the role of noncoding RNAs in gliomas has only been partially revealed. We discuss the repercussion of epigenetic alterations underlying deregulated molecular pathways in the pathogenesis and evolution of gliomas and their impact on management of patients. PMID- 22778948 TI - Effects of somatic mutations in the C-terminus of insulin-like growth factor 1 receptor on activity and signaling. AB - The insulin-like growth factor I receptor (IGF1R) is overexpressed in several forms of human cancer, and it has emerged as an important target for anticancer drug design. Cancer genome sequencing efforts have recently identified three somatic mutations in IGF1R: A1374V, a deletion of S1278 in the C-terminal tail region of the receptor, and M1255I in the C-terminal lobe of the kinase catalytic domain. The possible effects of these mutations on IGF1R activity and biological function have not previously been tested. Here, we tested the effects of the mutations on the in vitro biochemical activity of IGF1R and on major IGF1R signaling pathways in mammalian cells. While the mutations do not affect the intrinsic tyrosine kinase activity of the receptor, we demonstrate that the basal (unstimulated) levels of MAP kinase and Akt activation are increased in the mutants (relative to wild-type IGF1R). We hypothesize that the enhanced signaling potential of these mutants is due to changes in protein-protein interactions between the IGF1R C-terminus and cellular substrates or modulators. PMID- 22778949 TI - From Transcriptome to Noncoding RNAs: Implications in ALS Mechanism. AB - In the last years, numerous studies have focused on understanding the metabolism of RNA and its implication in disease processes but abnormal RNA metabolism is still unknown. RNA plays a central role in translating genetic information into proteins and in many other catalytic and regulatory tasks. Recent advances in the study of RNA metabolism revealed complex pathways for the generation and maintenance of functional RNA in amyotrophic lateral sclerosis (ALS). Interestingly, perturbations in RNA processing have been described in ALS at various levels such as gene transcription, mRNA stabilization, transport, and translational regulations. In this paper, we will discuss the alteration of RNA profile in ALS disease, starting from transcription, the first step leading to gene expression, through the posttranscriptional regulation, including RNA/DNA binding proteins and aberrant exon splicing to protein noncoding RNAs, as lncRNA and microRNA. PMID- 22778950 TI - Access and Barriers to Healthcare Vary among Three Neighboring Communities in Northern Honduras. AB - Objective. The aim of this study is to describe and compare access and barriers to health services in three proximal yet topographically distinct communities in northern Honduras served by the nonprofit organization the Honduras Outreach Medical Brigada Relief Effort (HOMBRE). Methods. Study personnel employed a 25 item questionnaire in Spanish at the point of care during HOMBRE clinics in Coyoles, Lomitas, and La Hicaca (N = 220). We describe and compare the responses between sites, using Chi-squared and Fisher Exact tests. Results. Respondents in Lomitas demonstrated the greatest limitations in access and greatest barriers to care of all sites. Major limitations in access included "never" being able to obtain a blood test, obtain radiology services, and see a specialist. Major barriers were cost, distance, facility overcrowding, transportation, being too ill to go, inability to take time off work, and lack of alternate childcare. Conclusions. Despite being under the same local health authority, geographically remote Honduran communities experience greater burdens in healthcare access and barriers than neighboring communities of the same region. PMID- 22778952 TI - Influence of birth weight on the renal development and kidney diseases in adulthood: experimental and clinical evidence. AB - Several clinical and experimental studies support the hypothesis that foetal programming is an important determinant of nephropathy, hypertension, coronary heart disease, and type 2 diabetes during adulthood. In this paper, the renal repercussions of foetal programming are emphasised, and the physiopathological mechanisms are discussed. The programming of renal diseases is detailed based on the findings of kidney development and functional parameters. PMID- 22778951 TI - Focal adhesion-chromatin linkage controls tumor cell resistance to radio- and chemotherapy. AB - Cancer resistance to therapy presents an ongoing and unsolved obstacle, which has clear impact on patient's survival. In order to address this problem, novel in vitro models have been established and are currently developed that enable data generation in a more physiological context. For example, extracellular-matrix- (ECM-) based scaffolds lead to the identification of integrins and integrin associated signaling molecules as key promoters of cancer cell resistance to radio- and chemotherapy as well as modern molecular agents. In this paper, we discuss the dynamic nature of the interplay between ECM, integrins, cytoskeleton, nuclear matrix, and chromatin organization and how this affects the response of tumor cells to various kinds of cytotoxic anticancer agents. PMID- 22778953 TI - Potential inaccuracies in chloride measurements in patients with severe metabolic acidosis. AB - Background. To address the cause(s) of the significant differences in chloride (Cl(-)) concentrations between point-of-care blood gas analyzers and central laboratory analyzers. Methods. Cl(-) concentrations measured simultaneously by a blood gas analyzer (ABL800 FLEX) and a central laboratory analyzer (Hitachi7600) were collected in patients with severe acidemia (pH < 7.20) (n = 32) and were examined for correlations between differences in Cl(-) and factors associated with the acid-base status. Cl(-) concentrations were measured with both analyzers for samples with different concentrations of lactate, inorganic phosphate, or bicarbonate (HCO(3) ( -)). Results. The differences in Cl(-) concentrations were correlated with HCO(3) ( -) concentrations (r = 0.72, P < 0.0001) and anion gap (r = 0.69, P < 0.0001). Only the addition of HCO(3) ( -) proportionately increased Cl(-) levels measured by a Hitachi7600, but it did not affect those measured by an ABL800FLEX. Conclusion. Cl(-) measurements with some analyzers may be influenced by HCO(3) ( -) concentrations, which could result in the observed discrepancies. PMID- 22778954 TI - Is the antiproteinuric effect of cyclosporine a independent of its immunosuppressive function in T cells? AB - The antiproteinuric effect of cyclosporine A(CsA) has been believed to result from its immunosuppressive effect on the transcription factor NFAT in T cells. However, current evidences supporting this hypothesis are missing. A recent study showed that CsA has a direct antiproteinuric effect on podocytes, suggesting a novel non-immunosuppressive mechanism for CsA's antiproteinuric effect. Conditional NFATc1 activation in podoyctes per se is sufficient to induce proteinuria in mice, indicating that NFAT activation in podocytes is a critical pathogenic molecular event leading to podocyte injury and proteinuria. Meanwhile, evidence showed that TRPC6-mediated Ca(2+) influx stimulates NFAT-dependent TRPC6 expression. Altogether, these advances in podocyte research indicate that calcineurin-NFAT signal or calcineurin-synaptopodin axis has a direct proteinuric effect on podocytes which raises the possibility of developing specific antiproteinuric drugs that lack the unwanted effects of calcineurin or NFAT inhibition. PMID- 22778955 TI - Plasma fractionation enriches post-myocardial infarction samples prior to proteomics analysis. AB - Following myocardial infarction (MI), matrix metalloproteinase-9 (MMP-9) levels increase, and MMP-9 deletion improves post-MI remodeling of the left ventricle (LV). We provide here a technical report on plasma-analysis from wild type (WT) and MMP-9 null mice using fractionation and mass-spectrometry-based proteomics. MI was induced by coronary artery ligation in male WT and MMP-9 null mice (4-8 months old; n = 3/genotype). Plasma was collected on days 0 (pre-) and 1 post-MI. Plasma proteins were fractionated and proteins in the lowest (fraction 1) and highest (fraction 12) molecular weight fractions were separated by 1-D SDS-PAGE, digested in-gel with trypsin and analyzed by HPLC-ESI-MS/MS on an Orbitrap Velos. We tried five different fractionation protocols, before reaching an optimized protocol that allowed us to identify over 100 proteins. Serum amyloid A substantially increased post-MI in both genotypes, while alpha-2 macroglobulin increased only in the null samples. In fraction 12, extracellular matrix proteins were observed only post-MI. Interestingly, fibronectin-1, a substrate of MMP-9, was identified at both day 0 and day 1 post-MI in the MMP-9 null mice but was only identified post-MI in the WT mice. In conclusion, plasma fractionation offers an improved depletion-free method to evaluate plasma changes following MI. PMID- 22778957 TI - Interleukin-1 Two-Locus Haplotype Is Strongly Associated with Severe Chronic Periodontitis among Yemenis. AB - Aim. To assess IL-1A C[-889]T and IL-1B C[3954]T genotypes as well as haplotypes in relation to sever chronic periodontitis (SCP) among Yemenis. Materials and Methods. 40 cases with SCP and 40 sex- and age-matched controls were included; all were nonsmokers and free of systemic diseases. Genotyping at each locus was performed using an established PCR-RFLP assay. The Haploview and SimHap software were used to assess data for Hardy-Weinberg's equilibrium (HWE) and linkage disequilibrium (LD) and to obtain subject-level haplotypes. Multiple logistic regression was used to seek for associations in dominant, additive, and recessive models. Results. Mean plaque index (MPI) showed the strongest association with SCP (OR = 16). A significant LD was observed in the cases (D' = 0.80 and r(2) = 0.47). The genotype at each locus showed significant association with SCP in the recessive model (TT versus TC + CC) even after adjustment for MPI (OR = 6.29 & 461, resp.). The C-T haplotype conferred protection against SCP in a dominant manner (OR = 0.16). On the other hand, the T-T haplotype in double dose (recessive model) showed strong association with CP (OR = 15.6). Conclusions. IL 1 two-locus haplotype is associated with SCP in Yemenis. Haplotype-based analysis may be more suited for use in genetic association studies of periodontitis. PMID- 22778956 TI - Application of proteomics to soft tissue sarcomas. AB - Soft tissue sarcomas are rare and account for less than 1% of all malignant cancers. Other than development of intensive therapies, the clinical outcome of patients with soft tissue sarcoma remains very poor, particularly when diagnosed at a late stage. Unique mutations have been associated with certain soft tissue sarcomas, but their etiologies remain unknown. The proteome is a functional translation of a genome, which directly regulates the malignant features of tumors. Thus, proteomics is a promising approach for investigating soft tissue sarcomas. Various proteomic approaches and clinical materials have been used to address clinical and biological issues, including biomarker development, molecular target identification, and study of disease mechanisms. Several cancer associated proteins have been identified using conventional technologies such as 2D-PAGE, mass spectrometry, and array technology. The functional backgrounds of proteins identified were assessed extensively using in vitro experiments, thus supporting expression analysis. These observations demonstrate the applicability of proteomics to soft tissue sarcoma studies. However, the sample size in each study was insufficient to allow conclusive results. Given the low frequency of soft tissue sarcomas, multi-institutional collaborations are required to validate the results of proteomic approaches. PMID- 22778960 TI - Health-Related Social Control over Physical Activity: Interactions with Age and Sex. AB - Despite the disease prevention benefits of engaging in life-long regular physical activity, many adults remain sedentary. The social environment provides an important context for health and health behavior across the lifespan, as well as a potential point of intervention for increasing physical activity. Self-reports of perceived social support, social strain, positive social control, and negative social control were examined for their cross-sectional relationships to physical activity frequency in purposive samples of younger and older adults (N = 371, ages from 18 to 97, 68% women). Hierarchical regression analyses revealed that perceived support and perceived strain were not correlated with physical activity. However, age and sex interacted with social control, such that more positive social control was associated with more frequent physical activity for younger men. Furthermore, more positive and negative social control were significantly associated with less frequent physical activity for older men, while social control was not associated with physical activity among women. While younger men may be encouraged toward healthier behaviors by positive social control messages, social control attempts may backfire when targeting older men. Implications for physical activity promotion are discussed. PMID- 22778961 TI - Endoplasmic reticulum stress and lipid metabolism. PMID- 22778958 TI - HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions. AB - During the retrotranscription process, characteristic of all retroviruses, the viral ssRNA genome is converted into integration-competent dsDNA. This process is accomplished by the virus-coded reverse transcriptase (RT) protein, which is a primary target in the current treatments for HIV-1 infection. In particular, in the approved therapeutic regimens two classes of drugs target RT, namely, nucleoside RT inhibitors (NRTIs) and nonnucleoside RT inhibitors (NNRTIs). Both classes inhibit the RT-associated polymerase activity: the NRTIs compete with the natural dNTP substrate and act as chain terminators, while the NNRTIs bind to an allosteric pocket and inhibit polymerization noncompetitively. In addition to these two classes, other RT inhibitors (RTIs) that target RT by distinct mechanisms have been identified and are currently under development. These include translocation-defective RTIs, delayed chain terminators RTIs, lethal mutagenesis RTIs, dinucleotide tetraphosphates, nucleotide-competing RTIs, pyrophosphate analogs, RT-associated RNase H function inhibitors, and dual activities inhibitors. This paper describes the HIV-1 RT function and molecular structure, illustrates the currently approved RTIs, and focuses on the mechanisms of action of the newer classes of RTIs. PMID- 22778959 TI - Role of exercise therapy in prevention of decline in aging muscle function: glucocorticoid myopathy and unloading. AB - Changes in skeletal muscle quantity and quality lead to disability in the aging population. Physiological changes in aging skeletal muscle are associated with a decline in mass, strength, and inability to maintain balance. Glucocorticoids, which are in wide exploitation in various clinical scenarios, lead to the loss of the myofibrillar apparatus, changes in the extracellular matrix, and a decrease in muscle strength and motor activity, particularly in the elderly. Exercise therapy has shown to be a useful tool for the prevention of different diseases, including glucocorticoid myopathy and muscle unloading in the elderly. The purpose of the paper is to discuss the possibilities of using exercise therapy in the prevention of glucocorticoid caused myopathy and unloading in the elderly and to describe relationships between the muscle contractile apparatus and the extracellular matrix in different types of aging muscles. PMID- 22778962 TI - Involvement of inflammation and adverse vascular remodelling in the blood pressure raising effect of repeatedly heated palm oil in rats. AB - Oil thermoxidation during deep frying generates harmful oxidative free radicals that induce inflammation and increase the risk of hypertension. This study aimed to investigate the effect of repeatedly heated palm oil on blood pressure, aortic morphometry, and vascular cell adhesion molecule-1 (VCAM-1) expression in rats. Male Sprague-Dawley rats were divided into five groups: control, fresh palm oil (FPO), one-time-heated palm oil (1HPO), five-time-heated palm oil (5HPO), or ten time-heated palm oil (10HPO). Feeding duration was six months. Blood pressure was measured at baseline and monthly using tail-cuff method. After six months, the rats were sacrificed and the aortic arches were dissected for morphometric and immunohistochemical analyses. FPO group showed significantly lower blood pressure than all other groups. Blood pressure was increased significantly in 5HPO and 10HPO groups. The aortae of 5HPO and 10HPO groups showed significantly increased thickness and area of intima-media, circumferential wall tension, and VCAM-1 than other groups. Elastic lamellae were disorganised and fragmented in 5HPO- and 10HPO-treated rats. VCAM-1 expression showed a significant positive correlation with blood pressure. In conclusion, prolonged consumption of repeatedly heated palm oil causes blood pressure elevation, adverse remodelling, and increased VCAM 1, which suggests a possible involvement of inflammation. PMID- 22778963 TI - Carotid velocities determine cerebral blood flow deficits in elderly men with carotid stenosis <50%. AB - To examine if mild carotid stenosis correlates with silent vascular brain changes, we studied a prospective population-based cohort "Men born in 1914." Data from followups at ages 68 and 81, have been used. Carotid ultrasound was performed at age 81, and cerebral blood flow (CBF) was measured with SPECT at age 82. Out of 123 stroke-free patients, carotid stenosis <50% was observed in 94% in the right and 89% in the left internal carotid arteries (ICAs). In these subjects, Peak Systolic Velocities in ICA correlated negatively with CBF in a majority of several brain areas, especially in mesial temporal area. Results were limited to normotensive until their seventies, who developed late-onset hypertension with a subsequent blood pressure, pulse pressure, and ankle-brachial index growth. Elderly with asymptomatic carotid stenosis <50% and peak systolic velocities in ICA 0.7-1.3 m/s, should be offered an intensified pharmacotherapy to prevent stroke or silent cerebrovascular events. PMID- 22778964 TI - Selective gene expression analysis of muscular and vascular components in hearts using laser microdissection method. AB - Background. The heart consists of various kinds of cell components. However, it has not been feasible to separately analyze the gene expression of individual components. The laser microdissection (LMD) method, a new technology to collect target cells from the microscopic regions, has been used for malignancies. We sought to establish a method to selectively collect the muscular and vascular regions from the heart sections and to compare the marker gene expressions with this method. Methods and Results. Frozen left ventricle sections were obtained from Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHR-SP) at 24 weeks of age. Using the LMD method, the muscular and vascular regions were selectively collected under microscopic guidance. Real-time RT-PCR analysis showed that brain-type natriuretic peptide (BNP), a marker of cardiac myocytes, was expressed in the muscular samples, but not in the vascular samples, whereas alpha-smooth muscle actin, a marker of smooth muscle cells, was detected only in the vascular samples. Moreover, SHR-SP had significantly greater BNP upregulation than WKY (P < 0.05) in the muscular samples. Conclusions. The LMD method enabled us to separately collect the muscular and vascular samples from myocardial sections and to selectively evaluate mRNA expressions of the individual tissue component. PMID- 22778965 TI - Triggered rapid degradation of nanoparticles for gene delivery. AB - Effective gene delivery tools offer the possibility of addressing multiple diseases; current strategies rely on viruses or polyplexes. Encapsulation of DNA within nanoparticles is an attractive alternative method for gene delivery. We investigated the use of our recently developed Logic Gate Nanoparticle for gene delivery. The nanoparticles, composed of a dual pH response random copolymer (poly-beta-aminoester ketal-2), can undergo a two-step "in series" response to endosomal pH. The first sep is a hydrophobic-hydrophilic switch, which is followed immediately by rapid degradation. Rapid fragmentation is known to increase cytoplasmic delivery from nanoparticles. Therefore, we hypothesized that our Logic Gate Nanoparticles would enable increased gene delivery and expression relative to nanoparticles that degrade more slowly such as PLGA-based nanoparticles. Passive nanoparticle entry into cells was demonstrated by delivering Cy5-labeled pDNA encoding EGFP into HCT116, a colon carcinoma cell line. Flow cytometry analysis showed that cells are positive for Cy5-DNA nanoparticles and produced EGFP expression superior to PLGA nanoparticles. Inhibition of V-ATPases using bafilomycin A1 demonstrates that expression of EGFP is dependent on low endosomal pH. The advanced Logic Gate Nanoparticles offer new therapeutic possibilities in gene delivery and other applications where rapid release is important. PMID- 22778966 TI - Native and Complexed IGF-1: Biodistribution and Pharmacokinetics in Infantile Neuronal Ceroid Lipofuscinosis. AB - Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disorder of childhood characterized by selective death of cortical neurons. Insulin-like growth factor 1 (IGF-1) is important in embryonic development and is considered as a potential therapeutic agent for several disorders of peripheral and central nervous systems. In circulation IGF-1 is mainly bound to its carrier protein IGFBP-3. As a therapeutic agent IGF-1 has shown to be more active as free than complexed form. However, this may cause side effects during the prolonged treatment. In addition to IGFBP-3 the bioavailability of IGF-1 can be modulated by using mesoporous silicon nanoparticles (NPs) which are optimal carriers for sustained release of unstable peptide hormones like IGF-1. In this study we compared biodistribution, pharmacokinetics, and bioavailability of radiolabeled free IGF-1, IGF-1/IGFBP-3, and IGF-1/NP complexes in a Cln1-/- knockout mouse model. IGF-1/NP was mainly accumulated in liver and spleen in all studied time points, whereas minor and more constant amounts were measured in other organs compared to free IGF-1 or IGF-1/IGFBP-3. Also concentration of IGF-1/NP in blood was relatively high and stable during studied time points suggesting continuous release of IGF-1 from the particles. PMID- 22778967 TI - The Effect of Egg Consumption in Hyperlipidemic Subjects during Treatment with Lipid-Lowering Drugs. AB - Background. Limiting egg consumption to avoid high cholesterolemia is recommended to reduce risk of cardiovascular disease. However, recent evidences suggest that cholesterol from diet has limited influence on serum cholesterol. Objective. To assess the effect of egg consumption on lipid profiles in hyperlipidemic adults treated with lipid-lowering drugs. Material and Method. Sixty hyperlipidemic subjects, mean age of 61 years, who had been treated with lipid-lowering drugs. Every subject was assigned to consume additional 3 eggs per day with their regular diet for 12 weeks. Measurements for lipid profiles and body compositions were performed. Results. An additional consumption of 3 eggs per day for 12 weeks increased HDL-cholesterol by 2.46 +/- 6.81 mg/dL (P < 0.01) and decreased LDL cholesterol to HDL-cholesterol ratio by 0.13 +/- 0.46 (P < 0.05). No significant changes were found in other lipid profiles. Body weight and body mass index were significantly increased at 12th week by 0.52 +/- 1.83 kg and 0.31 +/- 0.99 kg/m(2), respectively (P < 0.05). Conclusion. In hyperlipidemic adults who were treated with lipid-lowering drugs, the consumption of additional 3 eggs per day to their regular diet will increase the level of HDL-cholesterol and decrease the ratio of LDL-cholesterol to HDL-cholesterol. PMID- 22778968 TI - Polymorphism of Myostatin Gene in Intron 1 and 2 and Exon 3, and Their Associations with Yearling Weight, Using PCR-RFLP and PCR-SSCP Techniques in Zel Sheep. AB - The aim of present study was to investigate myostatin gene polymorphism and its association with yearling weight records in Zel sheep using PCR-RFLP and PCR-SSCP methods. Blood samples were collected from 200 Zel sheep, randomly, and DNA was extracted using modified salting out method. Polymerase chain reaction was carried out to amplify 337, 222, and 311 bp fragments, respectively, comprising a part of exon 3, intron 1, and intron 2 of myostatin gene. In addition, exon 3 was digested by HaeIII enzyme under RFLP method, and introns 1 and 2 were studied using SSCP. Under RFLP method, all samples showed mm genotype. Under SSCP method, intron 1 was also monomorph but intron 2 was polymorph (AA, AB, and BB). The allelic frequencies for A and B were 75.5 and 24.5%, respectively. This locus was not in Hardy-Weinberg equilibrium (P < 0.05), and there was no significant effect of myostatin gene on yearling weights. PMID- 22778969 TI - Characterization of Autoantibodies against the E1alpha Subunit of Branched-Chain 2-Oxoacid Dehydrogenase in Patients with Primary Biliary Cirrhosis. AB - Primary biliary cirrhosis (PBC) is characterized by antimitochondrial antibodies (AMAs) that react with the lipoyl-containing E2 subunits of 2-oxoacid dehydrogenase complexes such as BCOADC and PDC. The lipoyl domains of E2 contain the major epitopes essential for immunopathology. However, the non-lipoyl containing E1 subunits are also frequently targeted. Since anti-E1 antibodies always appear in combination with anti-E2 antibodies, the mechanisms underlying the autoimmunity against E1 may be linked to, but distinct from, those against E2. Here, we demonstrate that intermolecular and intramolecular determinant spreading underlies the autoimmunity against E1. We performed characterizations and epitope mapping for anti-BCOADC-E1alpha antibodies from both the intermolecular and intramolecular points of view. The antibody reactivities form a cluster against the BCOADC complex that is distinct from that against the PDC complex, and the anti-BCOADC-E1alpha antibodies arise as part of the cluster against the BCOADC complex. Multiple epitopes are present on the surface of the BCOADC-E1alpha molecule, and the major epitope overlaps with the active center. Sera with anti-BCOADC-E1alpha antibodies strongly inhibited the enzyme activity. These findings suggest that the E1alpha subunit as part of the native BCOADC complex is an immunogen, and that determinant spreading is involved in the pathogenesis of AMA production. PMID- 22778970 TI - Management of anticoagulation for portal vein thrombosis in individuals with cirrhosis: a systematic review. AB - Non-neoplastic portal vein thrombosis (PVT) is an increasingly recognized complication of liver cirrhosis. It is often diagnosed fortuitously and can be either partial or complete. The clinical significance of PVT is not obvious except in some situations such as when patients are on the waiting list for liver transplantation. The only known therapy is anticoagulation which has been shown to permit the disappearance of thrombosis and to prevent further extension. Anticoagulation is a challenging therapy in individuals with liver cirrhosis because of the well-recognized coagulation abnormalities observed in that setting and because of the increased risk of bleeding, especially from gastrointestinal tract caused by portal hypertension. We herein review the current knowledge on that topic in order to highlight the advantages and disadvantages of the currently proposed therapeutic attitudes in face of the diagnosis of PVT in individuals with cirrhosis. PMID- 22778971 TI - Bioabsorbable pins for treatment of osteochondral fractures of the knee after acute patella dislocation in children and young adolescents. AB - A retrospective study was performed on the use of bioabsorbable pins in the fixation of osteochondral fractures (OCFs) after traumatic patellar dislocation in children. Eighteen children (13 females, 5 males) aged 11 to 15 years (mean age 13.1 years) with osteochondral fracture (OCF) of the knee joint were treated at the authors' institution. Followup ranged from 22 months to 5 years. Diagnosis was verified by X-ray and magnetic resonance imaging (MRI) of the knee and patella. In seven patients the osteochondral fragment was detached from the patella and in 11 it was detached from the lateral femoral condyle. All patients were subjected to open reduction and fixation of the lesion with bioabsorbable pins. Postoperatively, the knee was immobilized in a cast and all patients were mobilized applying a standardized protocol. Bone consolidation was successful in 17 of the 18 patients. Bioabsorbable pins reliably fix OCF in children and adolescents, demonstrating a high incidence of consolidation of the detached osteochondral fragment in short- and middle-term followup without requiring further operative procedures. PMID- 22778972 TI - Prevention of the musculoskeletal complications of hemophilia. AB - Hemophilia is an inherited disorder of clotting factor deficiencies resulting in musculoskeletal bleeding, including hemarthroses, leading to musculoskeletal complications. The articular problems of hemophiliac patients begin in infancy. These include: recurrent hemarthroses, chronic synovitis, flexion deformities, hypertrophy of the growth epiphyses, damage to the articular cartilage, and hemophilic arthropathy. The most commonly affected joints are the ankle, the knee, and the elbow. Hematologic prophylactic treatment from ages 2 to 18 years could avoid the development of hemophilic arthropathy if the concentration of the patient's deficient factor is prevented from falling below 1% of normal. Hemarthroses can be prevented by the administration of clotting factor concentrates (prophylaxis). However, high costs and the need for venous access devices in younger children continue to complicate recommendations for universal prophylaxis. Prevention of joint arthropathy needs to focus on prevention of hemarthroses through prophylaxis, identifying early joint disease through the optimal use of cost-effective imaging modalities and the validation of serological markers of joint arthropathy. Screening for effects on bone health and optimal management of pain to improve quality of life are, likewise, important issues. Major hemarthrosis and chronic hemophilic synovitis should be treated aggressively to prevent hemophilic arthropathy. PMID- 22778973 TI - Changes in the upper and lower pharyngeal airway spaces associated with rapid maxillary expansion. AB - Objectives. The primary objectives of this retrospective study were first to compare the upper and lower pharyngeal airway spaces between orthodontic patients with and without maxillary constriction and second to evaluate the effect of rapid maxillary expansion (RME) on these airway spaces. A secondary objective was to compare the mode of breathing between groups. Materials and Methods. The experimental (RME) group consisted of 30 patients (mean age, 14.2 +/- 1.3 years, 16 boys and 14 girls) with maxillary constriction who were treated with hyrax type RME. The control group comprised the records of age- and gender matched patients (mean age, 13.8 +/- 1.5 years, 16 boys and 14 girls) with no maxillary constriction but requiring nonextraction comprehensive orthodontic treatment. Cephalometric measurements in the sagittal dimension of upper and lower airway spaces for the initial and final records were recorded. Mode of breathing and length of treatment were also compared. Results. The sagittal dimension of the upper airway increased significantly in the RME group (mean = 1.3 mm) compared to the control group (mean = 0.5 mm), P = 0.016. However, there was no significant difference in the lower pharyngeal airway measurement between the RME group (mean = 0.2) and the control group (mean = 0.4), P = 0.30. There was no significant difference with respect to mode of breathing between the two groups (P = 0.79). Conclusion. Rapid maxillary expansion (RME) during orthodontic treatment may have a positive effect on the upper pharyngeal airway, with no significant change on the lower pharyngeal airway. PMID- 22778974 TI - The prevalence of dental anomalies in the Western region of saudi arabia. AB - Objective. The aim of this cross-sectional study was to investigate the prevalence of dental anomalies that could be a cause of malocclusion in the western region of Saudi Arabia. Materials and Methods. A retrospective study of 878 digital orthopantomograms (OPGs) taken of patients, age ranging between 12 and 30 years, who presented to treatment at the Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia between 2002 and 2011. The OPGs and dental records were reviewed for congenitally missing teeth, supernumerary teeth, impactions, ectopic eruption, transposition, germination, fusion, dilacerations, taurodontism, dens in dent, and any other unusual conditions that can be assessed with OPG. Results. The prevalence of patient that exhibited at least one dental anomaly was 396 (45.1%) patients. The prevalence of congenitally missing teeth was 226 (25.7%), impacted teeth 186 (21.1%), dilacerated teeth 10 (1.1%), supernumerary teeth 3 (0.3%), odontoma 1 (0.1%), and taurodontism was also 1 case (0.1%) of the total radiographs reviewed. Conclusions. Congenitally missing teeth were found to be the most prevalent anomaly (25.7%), and the second frequent anomaly was impacted teeth (21.1%), whereas root dilacerations, supernumerary teeth, and taurodontism were the least frequent anomalies (1.1%, 0.3% and 0.1%, resp.). PMID- 22778975 TI - Gastric ulceration in diabetes mellitus: protective role of vitamin C. AB - The effect of vitamin C administration on gastric acid secretion and ulcer in diabetic rats was studied. Vitamin C (200 mg/kg b.w.) was administered to both streptozotocin-induced diabetic and control groups orally for 28 days. Gastric acid secretion was measured and ulcer was induced using ethanol. Histological changes were observed in the stomach. Basal and stimulated acid secretion in diabetic control rat was significantly (P < 0.01) decreased when compared to vitamin C-treated diabetic group and control. Administration of vitamin C significantly (P < 0.05) increased the histamine-stimulated gastric acid secretion in diabetics than control while reduction in gastric secretion by ranitidine was similar compared with control. Vitamin C treatment significantly (P < 0.05) reduced ulcer index in diabetic group and increased mucus weight when compared with diabetic group which was also confirmed with photomicrographs. The mean body weight of diabetic rats treated with vitamin C was comparable to the control. The blood glucose level was significantly (P < 0.01) reduced in diabetic group given vitamin C (8.9 +/- 1.8 mMol/L) compared to the diabetic control (32.2 +/- 2.1 g). It is concluded that vitamin C is beneficial in improving gastric acid secretion and protects against ulceration in streptozotocin-induced diabetes mellitus in rats due to its antioxidant potential. PMID- 22778976 TI - In Crohn's Disease, Anti-TNF-alpha Treatment Changes the Balance between Mucosal IL-17, FOXP3, and CD4 Cells. AB - Aim. In Crohn's disease (CD), anti-TNF-alpha treatment is a potent medication. We aimed to characterize the effect of anti-TNF-alpha treatment on T effector and regulatory cells. Material and Methods. We studied T-effector and regulatory cells on cellular and mRNA levels in intestinal biopsy samples from 13 Crohn's disease patient. Biopsies were obtained at baseline and 3 months after anti-TNF alpha treatment, and from 14 inflammation-free control subjects. Results. Patients had higher numbers of ileal IL-17(+) and forkhead box P3 (FOXP3)(+) cells than did control subjects, both before ( P <= 0.001 and P <= 0.05, resp.) and after the anti-TNF-alpha treatment (P <= 0.01, P <= 0.01). Intestinal interferon-gamma and IL-17 mRNA expression was higher in Crohn's disease and remained elevated after anti-TNF-alpha treatment. The ratio of IL-17(+) cells to CD4(+) cells decreased (P <= 0.05) and compared to baseline the ratio of IL-17(+) cells to FOXP3(+) was lower after treatment (P <= 0.05). Conclusions. TNF-alpha blocking agents improved intestinal balance between IL-17(+) T-effector and regulatory T cells, although intestinal IL-17 upregulation remained elevated. PMID- 22778977 TI - Endoscopic Submucosal Dissection for Treatment of Patients Aged 75 Years and over with Esophageal Cancer. AB - Background. Although many reports concerning the use of endoscopic submucosal dissection (ESD) for esophageal cancer have been published, the feasibility of ESD in elderly patients has not been reported. Therefore, we evaluated the efficacy and safety of ESD for treating early esophageal cancer in elderly patients. Methods. A total of 62 cases (52 men, 10 women; mean age +/- standard deviation, 66.5 +/- 10.5 years) for which the first resection (first treatment) of esophageal cancer was performed by ESD were identified from 77 consecutive esophageal epithelial cancers in 67 patients treated at our institution from January 2005 to March 2011. Patient characteristics, clinical findings, and outcomes were retrospectively assessed for patients separated into older (aged 75 years and older) and younger (aged under 75 years) groups. Results. No significant differences in specimen size, procedure time, median length of the hospital stay (8 versus 9 days; P = 0.252) or procedure-associated complications (8% versus 27%; P = 0.264) were observed between the older (n = 13) and younger (n = 49) groups. Lesions were completely resected in 12 patients and 44 patients, in the younger and older groups, respectively, and the curative resection rate was 77% and 59%, respectively. There were no deaths attributable to procedure associated complications. Conclusions. ESD is an effective treatment for early esophageal cancer and is well tolerated by elderly patients. PMID- 22778978 TI - Functional abdominal bloating with distention. AB - Ten to 25% of healthy persons experience bloating. It is particularly common in persons with the irritable bowel syndrome and constipation. While the cause of bloating remains unknown old explanations such as a excessive intestinal gas, exaggerated lumbar lordosis and psychiatric problems have been disproved. New suggestions include recent weight gain, weak or inappropriately relaxed abdominal muscles, an inappropriately contracted diaphragm and retained fluid in loops of distal small bowel. No treatment is of unequivocal benefit but a low FODMAPs diet, probiotics and the non-absorbable antibiotic rifaximin offer some hope. Treatment by weight loss, abdominal exercise, prokinetics and girdles need more study. PMID- 22778980 TI - Pattern of beta-Thalassemia and Other Haemoglobinopathies: A Cross-Sectional Study in Bangladesh. AB - Thalassemia and other structural haemoglobinopathies are the major erythrocyte formation disorder prevalent in certain parts of the world including Bangladesh. We investigated 600 cases of anaemic patients referred from various parts of the country for diagnosis and counselling during 3 months (April to June 2011) of time. The most common form of haemoglobin (Hb) formation disorder observed in 600 subjects studied was beta-thalassemia minor (21.3%). Two other conditions, such as E-beta-Thalassemia and HbE trait, were also fairly common (13.5 and 12.1%, resp.) in the total subjects studied. Other forms of haemoglobin formation disorders observed were HbE disease (9.2%), Hb D/S trait (0.7%), beta-thalassemia major (0.5%), and delta-beta-thalassemia (0.5%). The majority of the haemoglobinopathies belonged to neonatal to childhood period (0-15 years), followed by reproductive age group (16-45 years). Few old-age (46+ years) cases were also detected in course of clinical complications. PMID- 22778981 TI - PP13 and PAPP-A in the First and Second Trimesters: Predictive Factors for Preeclampsia? AB - Background. Preeclampsia affects 5-6% of all pregnancies. Predictive factors of preeclampsia can be helpful in early diagnosis of this disease. In this study the predictive values of biochemical markers placenta protein 13 (PP13) and pregnancy associated plasma protein A (PAPP-A) have been assessed in early diagnosis of preeclampsia. Methods. This case-control study was conducted on 1500 women who presented to a healthcare center of Sari, Iran, between 2010 and 2011. Blood samples were drawn in weeks 11-13 and 24-28 of pregnancy. Of them who developed preeclampsia were considered as case group. A control group consisted of similar women regarding mean age, body mass index (BMI), and pregnancy age. PAPP-A and PP13 serum levels were measured. Data were analyzed using proper statistical tests. Results. PAPP-A and PP13 serum levels were significantly lower in both the first and second trimesters in women who developed preeclampsia (P < 0.001). The cumulative value of all four variables with cut-off point of 238.5 has sensitivity, specificity of 91.0%, and undercurve surface of 0.968 which is the most diagnostic value for preeclampsia. Conclusion. It is possible to advantage measuring of PAPP-A and PP13 in the first and second trimesters especially their cumulative values in both trimesters for prediction of the incidence of preeclampsia. PMID- 22778979 TI - Eradication Treatment of Helicobacter pylori Infection: Its Importance and Possible Relationship in Preventing the Development of Gastric Cancer. AB - Helicobacter pylori is the most important carcinogen for gastric adenocarcinoma. Bacterial virulence factors are essential players in modulating the immune response involved in the initiation of carcinogenesis in the stomach; host genetic factors contribute to the regulation of the inflammatory response and to the aggravation of mucosal damage. In terms of environmental factors, salt intake and smoking contribute to the development of lesions. Various therapeutic schemes are proposed to eradicate H. pylori infection, which could potentially prevent gastric cancer, offering the greatest benefit if performed before premalignant changes of the gastric mucosa have occurred. PMID- 22778982 TI - A Review of Outcome Data concerning Children Born following Assisted Reproductive Technologies. AB - Assisted reproductive technologies (ARTS) are used for more than 30 years to help infertile couples. Concerns about long-term health of children conceived following ART have led to start follow-up studies. Despite methodological limitations and discrepant results, many of the studies and meta-analyses have reported an increased risk of birth defects after ART. Etiologies may be multiple births, a major drawback of ART, parents' subfertility, or technologies themselves. Prematurity and intrauterine growth retardation (IUGR) seem to cause most of the pathologies reported in ART children. Nevertheless, epigenetic disorders need to be followed up since increases of imprinting diseases were reported. Consequently, alteration of gametes and early embryo development with ART may have consequences on children health since periconceptional period is critical for long-term development. Yet general condition of most of children conceived with ART is reassuring, but long-term followup is still strongly needed. PMID- 22778983 TI - The Newest Hypothesis about Vitiligo: Most of the Suggested Pathogeneses of Vitiligo Can Be Attributed to Lack of One Factor, Zinc-alpha2-Glycoprotein. AB - Zinc-alpha2-glycoprotein (ZAG) is a recently identified adipokine, assigned to the chromosome 7q22.1. It is a multidisciplinary protein, which is secreted in various body fluids. The ZAG plays roles in lipolysis, regulation of metabolism, cell proliferation and differentiation, regulation of melanin synthesis, cell adhesion, immunoregulation, and so forth. Vitiligo is the most common depigmenting skin disorder, characterized by acquired, progressive, and circumscribed amelanosis of the skin and hair. It commonly begins in childhood or young adulthood. The pathogenesis of this disorder is uncertain, but it appears to be dependent on the interaction of genetic, immunological, and neurological factors. For the first time, we pointed the probable association between ZAG and vitiligo. Herein, I have described this association in different views. By confirming this association, a surprising progression will occur in the treatment of this prevalent debilitating disease. PMID- 22778984 TI - C-Peptide reduces mitochondrial superoxide generation by restoring complex I activity in high glucose-exposed renal microvascular endothelial cells. AB - Hyperglycemia-mediated microvascular damage has been proposed to originate from excessive generation of mitochondrial superoxide in endothelial cells and is the suggested mechanism by which the pathogenesis of diabetes-induced renal damage occurs. C-peptide has been shown to ameliorate diabetes-induced renal impairment. Yet, the mechanisms underlying this protective benefit remain unclear. The objective of this study was to determine whether C-peptide affords protection to renal microvascular endothelial cell mitochondria during hyperglycemia. Conditionally immortalized murine renal microvascular endothelial cells (MECs) were exposed to low (5.5 mM) or high glucose (25 mM) media with either C-peptide (6.6 nM) or its scrambled sequence control peptide for 24 or 48 hours. Respiratory control ratio, a measure of mitochondrial electrochemical coupling, was significantly higher in high glucose renal MECs treated with C-peptide than those of high glucose alone. C-peptide also restored high glucose-induced renal MEC mitochondrial membrane potential changes back to their basal low glucose state. Moreover, C-peptide prevented the excessive mitochondrial superoxide generation and concomitant reductions in mitochondrial complex I activity which are mediated by the exposure of the renal MECs to high glucose. Together, these data demonstrate that C-peptide protects against high glucose-induced generation of mitochondrial superoxide in renal MECs via restoration of basal mitochondrial function. PMID- 22778985 TI - The Missing Link between Juvenile Delinquency and Pediatric Posttraumatic Stress Disorder: An Attachment Theory Lens. AB - The present paper reviews pediatric posttraumatic stress disorder, emphasizing the relational basis of the disorder and highlighting the missing link between juvenile delinquency and trauma. The first part of the paper defines trauma and the diagnostic criteria for PTSD, noting child-specific features. The second part reviews the literature emphasizing the relational and attachment relevant nature of trauma. The third part explores psychological mechanisms for how attachment relations could affect trauma responses. Attachment relations (1) shape core schemas of the world, others, and the self and (2) foster emotional engagement or disengagement, both of which have been associated with traumatic responses. The most empirically supported pediatric trauma treatment, trauma-focused cognitive behavioral therapy (TF-CBT), acknowledges the attachment figure's influence and includes treating and training the parent and conjoint child-parent discussion. The next section reviews the noteworthy link between juvenile delinquency and trauma history. More awareness of trauma and PTSD in children and adolescents is recommended to effectively address juvenile delinquency. The review ends with a few helpful points for practicing pediatricians regarding childhood trauma. PMID- 22778986 TI - Morbidity and mortality of caustic ingestion in rural children: experience in a new cardiothoracic surgery unit in Nigeria. AB - Background. Inspite of the fact that accidental caustic ingestion is an entirely easily preventable problem, it has however persisted in rural Nigerian communities because the commonly implicated agent which is caustic soda (sodium hydroxide, NaOH) is sold in open markets without restrictive legislations. This study aims to identify the perpetuating factors of paediatric caustic ingestion and recommend preventive measures. Method. Retrospective analysis of clinical records of our paediatric patients who presented following caustic ingestion between November 2006 and November 2010 was made for demography, socioeconomic status of parent(s), caustic substance ingested with amount (where known), circumstance of ingestion, means of oesophageal evaluation, treatment and outcome. Results. There were 16 paediatric cases of caustic ingestion during the study period with age ranging from 1 to 18 years with mode in the 1-3 years group and male : female ratio 4.3 : 1. In 100% of the cases, the caustic ingestion was accidental, while caustic soda was the agent in 93.7%, and 87.5% of the parents were into local soap and detergent production. In all patients, the oesophagus was evaluated with late barium swallow/meal and oesophagoscopy before treatment. Conclusion. Caustic ingestion among rural children in Nigeria can be prevented. PMID- 22778988 TI - Streptococcal pharyngitis: a prospective study of compliance and complications. AB - Background. Uncertainty exists concerning the necessity of 10-day antibiotic treatment of group A beta hemolytic streptococcus (GABHS) pharyngitis. Objective. To assess the incidence of GABHS recurrence and suppurative and nonsuppurative complications in relation to compliance. Methods. (Design). Prospective cohort observational study. (Subjects). 2,000 children aged 6 months to 18 years with sore throat and positive GABHS culture. (Main Outcome Measures). Recurrence of symptomatic culture positive GABHS pharyngitis, incidence of suppurative, and long-term, regional, nonsuppurative complications of GABHS pharyngitis, over a ten year period. Results. 213 (11%) of the children received no treatment. Most children received antibiotics for only 4-6 days (in correlation with the duration of fever, which in most cases lasted up to 3 days). Three hundred and six (15.3%) children had clinically diagnosed recurrent tonsillopharyngitis; 236 (12.3%) had positive GABHS findings within 10 to 14 days and thirty-four (1.7%) within 21-30 days after the index positive GABHS culture. The remaining 1.3% had no positive culture despite the clinical findings. Almost all recurrences [236 (11.6%)] occurred within 14 days and 156 (7.6%) in the fully treated group. The presence of fever during the first 3 days of the disease was the most significant predictor for recurrence. Other predictors were the age younger than 6 years and the presence of cervical lymphadenitis. No increase in the incidence of nonsuppurative or suppurative complications was noted during the 10-year follow up period, compared to the past incidence of those complications in Israel. Conclusions. Our data suggests that the majority of children discontinue antibiotics for GABHS tonsillopharyngitis a day or two after the fever subsides. The incidence of complications in our study was not affected by this poor compliance. PMID- 22778987 TI - Transthoracic echocardiography in children and young adults with congenital heart disease. AB - Transthoracic echocardiography (TTE) is the first-line tool for diagnosis and followup of pediatric and young adult patients with congenital heart disease (CHD). Appropriate use of TTE can reduce the need for more invasive modalities, such as cardiac catheterization and cardiac magnetic resonance imaging. New echocardiographic techniques have emerged more recently: tissue Doppler imaging, tissue tracking (strain and strain rate), vector velocity imaging (VVI), myocardial performance index, myocardial acceleration during isovolumic acceleration (IVA), the ratio of systolic to diastolic duration (S/D ratio), and two dimensional measurements of systolic right ventricular (RV) function (e.g., tricuspid annular plane systolic excursion, TAPSE). These may become valuable indicators of ventricular performance, compliance, and disease progression. In addition, three-dimensional (3D) echocardiography when performed for the assessment of valvular function, device position, and ventricular volumes is being integrated into routine clinical care. In this paper, the potential use and limitations of these new echocardiographic techniques in patients with CHD are discussed. A particular focus is on the echocardiographic assessment of right ventricular (RV) function in conditions associated with increased right ventricular volume (e.g., pulmonary regurgitation after tetralogy of Fallot repair) or pressure (e.g., pulmonary hypertension) in children and young adults. PMID- 22778989 TI - Orbital IgG4-Related Disease: Clinical Features and Diagnosis. AB - Orbital IgG4-related disease, which can occur in adults of any age, is characterized by IgG4-positive lymphoplasmacytic infiltrations in ocular adnexal tissues. The signs and symptoms include chronic noninflammatory lid swelling and proptosis. Patients often have a history of allergic disease and elevated serum levels of IgG4 and IgE as well as hypergammaglobulinemia. Orbital IgG4-related disease must be differentiated from idiopathic orbital inflammation and ocular adnexal marginal zone B-cell lymphoma to ensure appropriate and effective treatment. Systemic steroid therapy decreases the size of the lesions, but relapse often occurs when systemic steroid therapy is discontinued. PMID- 22778990 TI - Prevalence and Risk Factors of Discordance between Left- and Right-Hip Bone Mineral Density Using DXA. AB - To determine the prevalence of significant left-right differences in hip bone mineral density (BMD), and the impact of this difference on osteoporosis diagnosis, we measured bilateral proximal femora using dual energy X-ray absorptiometry (DXA) in 3481 subjects (608 males, 2873 females). The difference between left and right hip was considered significant if it exceeded the smallest detectable difference (SDD) for any of the three hip subregions. Contralateral femoral BMD was highly correlated at all measuring sites (r = 0.92-0.95). However, significant left-right differences in BMD were common: the difference exceeded the SDD for 54% of patients at total hip, 52.1% at femoral neck, and 57.7% at trochanter. The prevalence of left-right differences was greater in participants >65 years. For 1169 participants with normal spines, 22 (1.9%) had discordant left-right hips in which one hip was osteoporotic; for 1349 patients with osteopenic spines, 94 (7%) had osteoporosis in one hip. Participants with BMI < 20 kg/m(2) were more likely to show major T-score discordance (osteoporosis in one hip and normal BMD in the other). Multiple regression analysis showed that the only significant statically parameter that persists after adjusting for all potential confounding parameters were age over 65 years. PMID- 22778991 TI - Understanding race and racism in nursing: insights from aboriginal nurses. AB - Purpose. Indigenous Peoples are underrepresented in the health professions. This paper examines indigenous identity and the quality and nature of nursing work life. The knowledge generated should enhance strategies to increase representation of indigenous peoples in nursing to reduce health inequities. Design. Community-based participatory research employing Grounded Theory as the method was the design for this study. Theoretical sampling and constant comparison guided the data collection and analysis, and a number of validation strategies including member checks were employed to ensure rigor of the research process. Sample. Twenty-two Aboriginal nurses in Atlantic Canada. Findings. Six major themes emerged from the study: Cultural Context of Work-life, Becoming a Nurse, Navigating Nursing, Race Racism and Nursing, Socio-Political Context of Aboriginal Nursing, and Way Forward. Race and racism in nursing and related subthemes are the focus of this paper. Implications. The experiences of Aboriginal nurses as described in this paper illuminate the need to understand the interplay of race and racism in the health care system. Our paper concludes with Aboriginal nurses' suggestions for systemic change at various levels. PMID- 22778992 TI - Benefit of BP Measurement in Pediatric ED Patients. AB - Introduction. Obtaining blood pressures in pediatric emergency department patients is the standard of care; however, there is little evidence to support its utility. This prospective study assesses the benefit of BP acquisition in patients <=5 years. Methods. Data were collected by the ED triage nurses on 649 patients in two community hospital EDs. Relationships between abnormal blood pressures and the patients' age, acuity, and calm versus not-calm emotional state were analyzed. Results. There were significant differences in the rate of elevated BPs in the calm and not-calm groups of patients. Overall, one- and two year-old patients were more likely to have elevated BPs than those in other age groups. Very few patients in the sample had hypotension (1%). There was no relationship between Emergency Severity Index (ESI) acuity level and an abnormal BP. Nineteen percent of calm patients had elevated BPs, with 3.6% of patients in the stage two class of hypertension. Conclusions. There is limited benefit in obtaining BPs in children age of five or less regardless of whether the child is calm or not in ESI acuity levels 3 and 4. PMID- 22778993 TI - Young stroke mortality in fiji islands: an economic analysis of national human capital resource loss. AB - Introduction. The objective of this study was to perform an economic analysis in terms of annual national human capital resource loss from young stroke mortality in Fiji. The official retirement age is 55 years in Fiji. Method. Stroke mortality data, for working-age group 15-55 years, obtained from the Ministry of Health and per capita national income figure for the same year was utilised to calculate the total output loss for the economy. The formula of output loss from the economy was used. Results. There were 273 stroke deaths of which 53.8% were of working-age group. The annual national human capital loss from stroke mortality for Fiji for the year was calculated to be F$8.85 million (US$5.31 million). The highest percentage loss from stroke mortality was from persons in their forties; that is, they still had more then 10 years to retirement. Discussion. This loss equates to one percent of national government revenue and 9.7% of Ministry of Health budget for the same year. The annual national human capital loss from stroke mortality is an important dimension in the overall economic equation of total economic burden of stroke. Conclusion. This study demonstrates a high economic burden for Fiji from stroke mortality of young adults in terms of annual national human capital loss. PMID- 22778994 TI - Current issues in atrial fibrillation. AB - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It places an enormous burden on the patients, caregivers, and the society at large. While the main themes in the care of an AF patient have not changed over the years and continue to focus on stroke prevention, control of the ventricular, rate and rhythm maintenance, there have been a number of new developments in each of these realms. This paper will discuss the "hot" topics in AF in 2012 including new and upcoming medical and invasive management strategies for this condition. PMID- 22778996 TI - High-Bandpass Filters in Electrocardiography: Source of Error in the Interpretation of the ST Segment. AB - Introduction. Artifactual variations in the ST segment may lead to confusion with acute coronary syndromes. Objective. To evaluate how the technical characteristics of the recording mode may distort the ST segment. Material and Method. We made a series of electrocardiograms using different filter configurations in 45 asymptomatic patients. A spectral analysis of the electrocardiograms was made by discrete Fourier transforms, and an accurate recomposition of the ECG signal was obtained from the addition of successive harmonics. Digital high-pass filters of 0.05 and 0.5 Hz were used, and the resulting shapes were compared with the originals. Results. In 42 patients (93%) clinically significant alterations in ST segment level were detected. These changes were only seen in "real time mode" with high-pass filter of 0.5 Hz. Conclusions. Interpretation of the ST segment in "real time mode" should only be carried out using high-pass filters of 0.05 Hz. PMID- 22778995 TI - The intrinsic autonomic nervous system in atrial fibrillation: a review. AB - The procedure of catheter ablation for the treatment of drug resistant atrial fibrillation (AF) has evolved but still relies on lesion sets intended to isolate areas of focal firing, mainly the myocardial sleeves of the pulmonary veins (PVs), from the rest of the atria. However the success rates for this procedure have varied inversely with the type of AF. At best success rates have been 20 to 30% below that of other catheter ablation procedures for Wolff-Parkinson-White syndrome, atrioventricular junctional re-entrant tachycardia and atrial flutter. Basic and clinical evidence has emerged suggesting a critical role of the ganglionated plexi (GP) at the PV-atrial junctions in the initiation and maintenance of the focal form of AF. At present the highest success rates have been obtained with the combination of PV isolation and GP ablation both as catheter ablation or minimally invasive surgical procedures. Various lines of evidence from earlier and more recent reports provide that both neurally based and myocardially based forms of AF can separately dominate or coexist within the context of atrial remodeling. Future studies are focusing on non-pharmacological, non-ablative approaches for the prevention and treatment of AF in order to avoid the substantive complications of both these regimens. PMID- 22778997 TI - Ischemic time as a predictor of physical recovery in the first months after heart transplantation. AB - Functional results after heart transplantation range from modest to spectacular improvement. Little is known about factors to predict functional result. This study aimed to identify these factors. We present a prospective study including all consecutive transplant recipients (n = 55) in a two-year period whose survival was greater than two months. Perioperative, donor, and recipient issues were systematically analyzed. Exercise capacity was assessed by symptom-limited treadmill exercise testing two months after transplantation. Exercise capacity was classified as satisfactory or poor depending on achieving or not 4.5 METs (metabolic equivalents), respectively. Thirty-three patients (60%) showed a good exercise capacity (>4.5 METs), whereas the remaining twenty-two patients (40%) were unable to exceed this threshold. The variables which correlated with exercise capacity in univariate analysis were recipient age, inotropic treatment, ischemic time, ventricular assist device, etiology, urgent transplant, and INTERMACS score. Among them only recipient age and ischemic time were proved to be correlated with exercise capacity in the multiple regression analysis. Thus, younger patients and those who had received an organ with shorter ischemic time showed greater exercise capacity after transplant. These findings strengthen the trend toward reducing ischemic time as much as possible to improve both survival and clinical recovery. PMID- 22778998 TI - Treatment options for metaplastic breast cancer. AB - Metaplastic breast cancer (MBC) is a malignancy characterized by the histologic presence of two or more cellular types, commonly a mixture of epithelial and mesenchymal components. MBC is rare relative to invasive ductal carcinoma (IDC), representing less than 1% of all breast cancers. Other than a lower rate of lymph node metastases, MBC tumors display poorer prognostic features relative to IDC. Due to its low incidence and pathological variability, the ideal treatment paradigm for MBC is unknown. Because of its rarity, MBC has been treated as a variant of IDC. Despite similar treatment regimens, however, patients with MBC have worse outcomes. Recent research is focused on biological differences between MBC and IDC and potential novel targets for chemotherapeutic agents. This paper serves as a summation of current literature on approaches to the multidisciplinary treatment of patients with MBC. PMID- 22778999 TI - Adverse Cell Culture Conditions Mimicking the Tumor Microenvironment Upregulate ABCG2 to Mediate Multidrug Resistance and a More Malignant Phenotype. AB - ABCG2 is an efflux transporter commonly found to overexpress in multidrug resistant (MDR) cancer cells. It is also believed to be a survival factor for cancer stem cells to drive tumor growth. Tumor microenvironment represents an attractive new drug target because it allows complex interaction between a tumor and its surrounding normal cells, molecules, and blood vessels, which all participate in tumor progression. Hypoxia, glucose deprivation and acidosis are the hallmarks of tumor microenvironment. This study investigated the upregulation of ABCG2 by these adverse growth conditions within the tumor microenvironment. Reporter gene assay revealed that a region within the ABCG2 promoter close to the reported HIF-1alpha response element is responsible for ABCG2 upregulation. Increased ABCG2 efflux activity was observed under the same conditions, subsequently leading to reduced response to ABCG2 substrate anticancer drug. Importantly, glucose deprivation and hypoxia were also found to enhance the resistance level of ABCG2-overexpressing resistant cells with pre-existing genetic and epigenetic MDR mechanisms. Hypoxia was further demonstrated to cause a more malignant anchorage-independent growth phenotype in the resistant cells, which can be abolished by knocking down ABCG2. A better understanding of ABCG2 regulation by the tumor microenvironment may help design novel strategies to improve treatment outcome. PMID- 22779000 TI - Appropriate patient selection in the management of common bile duct stones: when not to do ERCP. AB - Background. Magnetic resonance cholangiopancreatography (MRCP) is noninvasive and accurate for diagnosing intra common bile duct stones (ICSs). However, given limited access, routine utilisation for investigating all patients with gallstone disease is neither practical nor cost-effective. Conversely, many individuals proceed directly to endoscopic retrograde cholangiopancreatography (ERCP), an invasive test with appreciable complications. Aim. Identify factors associated with ICS in order to improve risk-stratification for MRCP/ERCP. Methods. All patients having undergone cholecystectomy between November 2007 and October 2008 were reviewed. High-risk features for ICS were predefined, and their true presence confirmed by ERCP or intraoperative cholangiogram. Multivariate logistic regression was performed on candidate risk features. Results. Of 231 patients, 10.4% had ICS. Defining a high-risk group with "both" biochemical and ultrasound risk factors predicted ICS with 92% specificity and also bore strong association (OR 8.88). However, isolated hyperbilirubinaemia, ultrasound impression of CBD stones, and clinical risk factors did not (OR 1.10, 0.97, and 1.26). Normal liver biochemistry and normal ultrasound had a NPV of 99.5% for ICS. Conclusions. Ultrasound impression of CBD calculi without ductal dilatation is not predictive of ICS. Patients with normal liver biochemistry and normal CBD diameter on ultrasound are unlikely to have ICS and should not proceed to ERCP. PMID- 22779001 TI - Locally advanced pancreatic head cancer: margin-positive resection or bypass? AB - Pancreatic cancer is a highly aggressive disease with poor survival. The only effective therapy offering long-term survival is complete surgical resection. In the setting of nonmetastatic disease, locally advanced tumors constitute a technical challenge to the surgeon and may result in margin-positive resection margins. Few studies have evaluated the implications of the latter in depth. The aim of this study was to compare the margin-positive situation to palliative bypass procedures and margin-negative resections in terms of perioperative and long-term outcome. By retrospective analysis of prospectively maintained data from 360 patients operated for pancreatic cancer at our institution, we provide evidence that margin-positive resection still yields a significant survival benefit over palliative bypass procedures. At the same time, perioperative severe morbidity and mortality are not significantly increased. Our observations suggest that pancreatic cancer should be resected whenever technically feasible, including, cases of locally advanced disease. PMID- 22779002 TI - Management of type 3 acromioclavicular joint dislocation: comparison of long-term functional results of two operative methods. AB - Introduction. Treatment of Rockwood Type 3 Acromioclavicular joint dislocation is controversial. We compared the long-term functional outcome of early repair of coracoclavicular ligament and internal fixation (Tension Band Wiring) with delayed reconstruction by modified Weaver-Dunn procedure for Type 3 dislocations. Method. Retrospective analysis of case records and telephone review to assess the long-term functional outcome by patient satisfaction and Oxford shoulder score. Results. We had 18 cases of Type 3 Acromioclavicular dislocations over a period of 10 years. 7 cases had Tension Band Wiring and 11 cases had modified Weaver Dunn procedure. Early repair group has higher risk (71%) of post operative complications compared to that of the delayed reconstruction group (9%). All 5 patients who developed postoperative complications in the early repair group required a second operation for metal work removal. Long-term functional results of both groups were comparable in terms of Oxford shoulder score and patient satisfaction. Conclusions. We recommend modified Weaver-Dunn procedure for failed conservative management of Grade 3 Acromioclavicular joint dislocation for the following reasons (1). better short-term functional outcome, low risk of complications and hence faster recovery (2). no need for a second surgery. PMID- 22779003 TI - Comparison of Patient's Satisfaction Level after Different Types of Posterior Chamber Intraocular Lens Implantation. AB - Objective. To compare patient's satisfaction level in performing routine activities during daylight and night vision after implantation with rigid, foldable, or rollable posterior chamber intraocular lens implants in uneventful cataract surgery. Design. Retrospective, cross-sectional. Place and Duration of Study. PNS SHIFA Hospital, Karachi, from Nov. 2009 to Nov. 2010. Methodology. 91 cataract surgery patients who had uneventful phacoemulsification, within the bag placement of intraocular lens and achieved best corrected visual acuity 6/9 or better were included in the study. Patients who developed postoperative complications were excluded. A specially designed questionnaire was used to assess patient's satisfaction level of vision for those who underwent cataract surgery at least 3 months ago. Finally, they were categorized into five groups ranging from "very good" to "very poor." SPSS version 16 was used to analyze the results. Results. There was a difference in satisfaction level between three groups. Vision was good in the day and the night with foldable posterior chamber intraocular lens implants. Conclusion. It was concluded that visual satisfaction level of patients who had foldable posterior chamber intraocular lens implantation was better during the day and night as compared to patients who had rigid or rollable posterior chamber intraocular lenses implantation. PMID- 22779004 TI - Renal Cell Carcinoma Update: News from the AUA, EAU, and ASCO Annual Meetings 2011. AB - Renal cell carcinoma (RCC) is one of the most important urologic malignancies with a continuously growing incidence and health economic relevance. In 2011, several hundred articles, abstracts, and lectures have been presented at the leading global urooncologic congresses. This review was composed to give an overview on the flood of novel findings dealing with diagnostics and therapy of both localized and advanced RCC. The most clinically relevant data are discussed in detail. PMID- 22779005 TI - Mechanism of repeat-associated microRNAs in fragile X syndrome. AB - The majority of the human genome is comprised of non-coding DNA, which frequently contains redundant microsatellite-like trinucleotide repeats. Many of these trinucleotide repeats are involved in triplet repeat expansion diseases (TREDs) such as fragile X syndrome (FXS). After transcription, the trinucleotide repeats can fold into RNA hairpins and are further processed by Dicer endoribonuclases to form microRNA (miRNA)-like molecules that are capable of triggering targeted gene silencing effects in the TREDs. However, the function of these repeat-associated miRNAs (ramRNAs) is unclear. To solve this question, we identified the first native ramRNA in FXS and successfully developed a transgenic zebrafish model for studying its function. Our studies showed that ramRNA-induced DNA methylation of the FMR1 5'-UTR CGG trinucleotide repeat expansion is responsible for both pathological and neurocognitive characteristics linked to the transcriptional FMR1 gene inactivation and the deficiency of its protein product FMRP. FMRP deficiency often causes synapse deformity in the neurons essential for cognition and memory activities, while FMR1 inactivation augments metabotropic glutamate receptor (mGluR)-activated long-term depression (LTD), leading to abnormal neuronal responses in FXS. Using this novel animal model, we may further dissect the etiological mechanisms of TREDs, with the hope of providing insights into new means for therapeutic intervention. PMID- 22779006 TI - Crossmodal recruitment of the ventral visual stream in congenital blindness. AB - We used functional MRI (fMRI) to test the hypothesis that blind subjects recruit the ventral visual stream during nonhaptic tactile-form recognition. Congenitally blind and blindfolded sighted control subjects were scanned after they had been trained during four consecutive days to perform a tactile-form recognition task with the tongue display unit (TDU). Both groups learned the task at the same rate. In line with our hypothesis, the fMRI data showed that during nonhaptic shape recognition, blind subjects activated large portions of the ventral visual stream, including the cuneus, precuneus, inferotemporal (IT), cortex, lateral occipital tactile vision area (LOtv), and fusiform gyrus. Control subjects activated area LOtv and precuneus but not cuneus, IT and fusiform gyrus. These results indicate that congenitally blind subjects recruit key regions in the ventral visual pathway during nonhaptic tactile shape discrimination. The activation of LOtv by nonhaptic tactile shape processing in blind and sighted subjects adds further support to the notion that this area subserves an abstract or supramodal representation of shape. Together with our previous findings, our data suggest that the segregation of the efferent projections of the primary visual cortex into a dorsal and ventral visual stream is preserved in individuals blind from birth. PMID- 22779008 TI - Accumulation and Elimination of Enrofloxacin and Ciprofloxacin in Tissues of Shrimp Litopenaeus vannamei under Laboratory and Farm Conditions. AB - This study aimed to quantify the accumulation and elimination of Enrofloxacin (ENRO) and Ciprofloxacin (CIPRO) in cultivated Litopenaeus vannamei under controlled laboratory and farm conditions. Laboratory- and farm-raised shrimp were given feed supplemented with 200 mg/kg ENRO for 14 days, followed by a 16 day diet without antibiotics. The levels of ENRO and CIPRO were analyzed by High Performance Liquid Chromatography (HPLC). In the laboratory, ENRO concentrations in the muscle and hepatopancreas reached a maximum (C(max)) of 0.54 +/- 0.26 MUg/g and 3.52 +/- 1.9 MUg/g, respectively; C(max) values for CIPRO in the laboratory were 0.18 +/- 0.13 MUg/g (muscle) and 1.05 +/- 0.20 MUg/g (hepatopancreas). In farmed shrimp, C(max) values for ENRO were 0.36 +/- 0.17 MUg/g muscle and 1.60 +/- 0.82 MUg/g in the hepatopancreas; CIPRO C(max) values were 0.03 +/- 0.02 MUg/g (muscle) and 0.36 +/- 0.08 MUg/g (hepatopancreas). Two to fourteen days were necessary to eliminate both antibiotics from muscular tissue and four to more fourteen days for complete elimination of the antibiotics from the hepatopancreas. These results should be considered in terms of minimum concentrations necessary to inhibit Vibrio bacteria to determine whether the current use of this antibiotic is effective in controlling disease. PMID- 22779007 TI - What we know and would like to know about CDKL5 and its involvement in epileptic encephalopathy. AB - In the last few years, the X-linked serine/threonine kinase cyclin-dependent kinase-like 5 (CDKL5) has been associated with early-onset epileptic encephalopathies characterized by the manifestation of intractable epilepsy within the first weeks of life, severe developmental delay, profound hypotonia, and often the presence of some Rett-syndrome-like features. The association of CDKL5 with neurodevelopmental disorders and its high expression levels in the maturing brain underscore the importance of this kinase for proper brain development. However, our present knowledge of CDKL5 functions is still rather limited. The picture that emerges from the molecular and cellular studies suggests that CDKL5 functions are important for regulating both neuronal morphology through cytoplasmic signaling pathways and activity-dependent gene expression in the nuclear compartment. This paper surveys the current state of CDKL5 research with emphasis on the clinical symptoms associated with mutations in CDKL5, the different mechanisms regulating its functions, and the connected molecular pathways. Finally, based on the available data we speculate that CDKL5 might play a role in neuronal plasticity and we adduce and discuss some possible arguments supporting this hypothesis. PMID- 22779009 TI - Ondansetron HCl Microemulsions for Transdermal Delivery: Formulation and In Vitro Skin Permeation. AB - Ondansetron HCl delivery through oral route suffers due to its low bioavailability due to first-pass metabolism. Therefore, the microemulsion-based transdermal delivery may be a better substitute for it. The pseudoternary phase diagrams were constructed to determine compositions of microemulsions, and ondansetron HCl microemulsions for transdermal delivery were developed using isopropyl myristate or oleic acid as the oil phase, Tween 80 as the surfactant, and isopropyl alcohol as the cosurfactant evaluated for in vitro skin permeation through excised porcine skin. The in vitro skin permeation from these formulated microemulsions was sustained over 24 hours. The microemulsion F-8 (contained 10% of isopropyl myristate as oil phase, 8% of aqueous phase, and 82% of surfactant phase containing Tween 80 and isopropyl alcohol, 3 : 1) showed the highest permeation flux of 0.284 +/- 0.003 MUg/cm(2)/hour. All these microemulsions followed the Korsmeyer-Peppas model (R(2) = 0.971 to 0.998) with non-Fickian, "anomalous" mechanism over a period of 24 hours. PMID- 22779010 TI - Development and evaluation of sustained release tablet of betahistine hydrochloride using ion exchange resin tulsion t344. AB - An attempt was made to sustain the release of Betahistine hydrochloride by complexation technique using strong cation-exchange resin, Tulsion T344. The drug loading onto ion-exchange resin was optimized for mixing time, activation, effect of pH, swelling time, ratio of drug : resin, and temperature. The resinate was evaluated for micromeritic properties and characterized using XRPD and IR. For resinate sustained release tablets were formulated using hydoxypropyl methylcellulose K100M. The tablets were evaluated for hardness, thickness, friability, drug content, weight variation, and in vitro drug release. Tablets thus formulated (Batch T-3) provided sustained release of drug over a period of 12 h. The release of Betahistine HCl from resinate controls the diffusion of drug molecules through the polymeric material into aqueous medium. Results showed that Betahistine HCl was formulated into a sustained dosage form as an alternative to the conventional tablet. PMID- 22779011 TI - Antibacterial Activity of Fistulin: A Protease Inhibitor Purified from the Leaves of Cassia fistula. AB - Plant protease inhibitors (PPIs) are one of the important components of a plant's defense machinery. PPIs are active against the insects and microbes which invade the plant. Cassia species possess anti-insecticidal and antimicrobial properties and this study was aimed at investigating the antibacterial efficacy of a PPI present in the leaves of Cassia fistula. A PPI, fistulin, was isolated from the leaves of C. fistula and purified by gel filtration chromatography. The antibacterial activity of the purified fistulin was studied against five bacterial strains, namely, Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli. The PPI was found to be very active against S. aureus, E. coli, B. subtilis, and K. pneumonia, and its efficacy was comparable to the standard drug, streptomycin sulphate. PMID- 22779012 TI - Chemical Composition and Antimicrobial Activities of Essential Oils from Nepeta cataria L. against Common Causes of Food-Borne Infections. AB - Nepeta cataria L. is traditionally consumed as a food additive. The effects of three different harvest stages of N. cataria essential oils (EOs) against most common causes of food-borne infections were evaluated by broth microdilution method as recommended by the Clinical and Laboratory Standards Institute (CLSI). The chemical composition of the EOs from N. cataria has been analyzed by gas chromatography/mass spectrometry (GC/MS). The analysis of the EOs indicated that 4a-alpha,7-alpha,7a-beta-nepetalactone (55-58%) and 4a-alpha,7-beta,7a-alpha nepetalactone (30-31.2%) were the major compounds of the EOs at all developmental stages. The results showed that the tested EOs exhibited antimicrobial activities against the food-borne pathogens at concentrations of 0.125-2 MUL/mL. Based on these results, the EO of N. cataria can possibly be used in food products as a natural preservative agent. PMID- 22779013 TI - Fabricating a soft liner-retained implant-supported palatal lift prosthesis for an edentulous patient: a case report. AB - This case report describes fabrication of a palatal lift prosthesis for a quadriplegic edentulous 30-year-old male with past head traumatic injury. We constructed an implant supported bar and used a soft-lining material for the maxillary palatal lift prosthesis to minimize the possibility of implant overloading and also provide a less complex and less expensive procedure for this patient. PMID- 22779014 TI - Mucormycosis of mandible with unfavorable outcome. AB - Mucormycosis is a fulminant fungal infection that occurs most often in diabetic and immunocompromised individuals. Our patient, with uncontrolled diabetes mellitus and multiple systemic disorders, developed postextraction mucormycosis of mandible, an extremely rare complication. An initial clinical and radiographic diagnosis of mandibular osteomyelitis was made and the lesion was treated medically and surgically with curettage and saucerisation. The specimen was sent for histopathological evaluation, which showed necrotic area containing broad aseptate fungal hyphae with right angle branching consistent with mucormycosis. The patient succumbed to multipleorgan failure secondary to septicemia. The disease is usually fatal with a poor survival rate; there is still paucity of literature on the definitive management of this disease involving the mandible. This paper emphasizes the need for correction of underlying immunodeficiency and early diagnosis with aggressive multimodality treatment approach to offer the best chance of survival. PMID- 22779015 TI - The First Case(s) of Botulism in Vienna in 21 Years: A Case Report. AB - We describe two linked cases of botulinum toxin intoxication to provide the clinician with a better idea about how botulism cases may present since early diagnosis and treatment are crucial in botulism. Botulinum toxin is the strongest neurotoxin known. METHODS: We review the available literature, the compiled clinical data, and observations. RESULTS: After a slow onset of clinical signs a married couple living in Vienna presented with dysphagia, difficulties in accommodation, inability to sweat, urinary and stool retention, dizziness, and nausea. They suffered intoxication with botulinum toxin type B. Botulism is a rarely occurring disease in Austria. In the last 21 years there were only twelve reported cases. CONCLUSION: Both patients went to a general practitioner as well as several specialists before they were sent to and correctly diagnosed at our outpatient department. To avoid long delays between intoxication and diagnosis we think it is crucial to advert to the complex symptoms a nonsevere intoxication with botulinum toxin can produce, especially since intoxications have become rare occurrences in the industrialized societies due to the high quality of industrial food production. PMID- 22779016 TI - Infantile amoebiasis: a case report. AB - Amoebiasis continues to be a major cause of morbidity and mortality in children in developing countries. Entamoeba histolytica infections are commonly observed in tropical and subtropical regions of the world including Iran. In developed countries Entamoeba histolytica infections are commonly seen in travelers, recent immigrants, homosexual men, and inmates of institutions. The disease is more severe in the two extremes of life. This paper paper describes a four-month-old male infant with Entamoeba histolytica presenting initially with refusal of feeds, hyperactive bowel sound, vomiting, and diarrhea. A fecal sample was positive for Entamoeba histolytica by Lugol's iodine solution and the concentration technique. He was successfully treated with metronidazole for 5 days. This case illustrates that Entamoeba species could be pathogenic in young infant; therefore, awareness of the infection, aggressive approach to diagnosis, and early initiation of treatment continue to be critical component of infection control. PMID- 22779017 TI - Management of Pseudohypoparathyroidism Type 1a during Pregnancy and Labor: A Case Report. AB - Pseudohypoparathyroidism is rare during pregnancy and poses multiple challenges related to its diagnosis and management during pregnancy. We hereby report a case of a young woman who was diagnosed to have type 1a pseudohypoparathyroidism. She was managed by multidisciplinary team and had good maternal and perinatal outcome. Management-related issues are discussed here in detail. PMID- 22779018 TI - First trimester abortion: a rare cause of intrauterine bony spicules. AB - Bony fragments in the uterus occur after second trimester termination of pregnancy following retained fetal bones. Very rarely, they can form following first trimester loss. Clinical symptoms range from pain, menstrual symptoms, and infertility. Ultrasound shows a hyperechoic shadow, and treatment is by curettage or hysteroscopic removal. PMID- 22779019 TI - Placental Teratoma Presenting as a Lobulated Mass behind the Neck of Fetus: A Case Report. AB - Placental teratoma is a rare nontrophoblastic benign tumour, which is thought to arise from germ cells. These tumours contain elements derived from multiple germ cell layers. We report a case of teratoma, where on ultrasound; there were two echogenic masses of 4 cm * 5 cm and 3 cm * 4 cm, arising from the placenta. Elective lower segment cesarean section was done in view of breech presentation at 38 weeks of gestation. Gross examination of the placenta showed two lobulated masses of 5 cm * 5 cm and 4 cm * 4.5 cm, respectively. Histopathological examination of the placenta was suggestive of teratoma of the placenta. The fetus was normal.The maternal and fetal outcome was good. PMID- 22779020 TI - Successful treatment with pemetrexed, Carboplatin, and bevacizumab for platinum resistant adenocarcinoma of the lung. AB - WE PRESENT TWO CASES OF RELAPSED ADENOCARCINOMA OF THE LUNG: a 50-year-old male and a 67-year-old male. Both patients had previously been treated with platinum containing systemic chemotherapy. In both cases, significant clinical efficacy was demonstrated with combination chemotherapy consisting of pemetrexed, carboplatin, and bevacizumab as salvage treatment. Adverse events were mild. This regimen might be a viable therapeutic option even after heavy treatment such as platinum-containing chemotherapy, especially for patients with preserved organ function and good performance status. PMID- 22779021 TI - Stercoral perforation requiring subtotal colectomy in a patient on methadone maintenance therapy. AB - Stercoral perforation of the colon is a rare but serious complication of chronic constipation. We present a case of stercoral perforation requiring subtotal colectomy in a 41-year-old female who had been on methadone maintenance for a history of long-term intravenous heroin use. Our case highlights the importance of prompt and thorough surgical intervention in the successful treatment of this rare condition. PMID- 22779022 TI - Acute gastric dilatation resulting in gastric emphysema following postpartum hemorrhage. AB - Acute gastric dilatation is a rare entity, with varying aetiologies the majority of which are benign. Delay in diagnosis and treatment could result in sequelae such as gastric emphysema (pneumatosis), emphysematous gastritis, gangrene, and perforation. Gastric emphysema as a result of a benign nongangrenous condition such as gastroparesis, adynamic ileus can be successfully managed conservatively. Here, we present an interesting case of acute gastric dilatation resulting in gastric emphysema following massive postpartum hemorrhage. PMID- 22779023 TI - Transcatheter closure of atrial septal defects in children, middle-aged adults, and older adults: failure rates, early complications; and balloon sizing effects. AB - Objectives. To compare the failure ratio and inhospital complications across three age groups of patients and to investigate the effects of balloon sizing on the success and the device diameter. Methods. This retrospective review was of 665 patients who had been listed for transcatheter-based closure of ASD between 1999 and 2010. The patients were divided into three age groups: children (<18 years; n = 183), adults (18-50 years; n = 337), and older adults (>50 years; n = 145). Procedural outcomes and early complications were reviewed. Use of balloon sizing was explored for its benefits. Results. Overall, failure of closure was 6.6% (n = 44). Use of balloon sizing tended to lead to a smaller device/defect ratio that was comparable to procedures without balloon sizing, though it did not predict the success rate (OR 1.4, 95% CI 0.7-2.3). Seven patients reported device embolization (1%). No mortalities were noted. In-hospital complications were 3.4%, with common complications, being vascular complications (1.4%) and cardiac arrhythmia (1.1%). No differences in failure rate or events were found among the three groups. Conclusion. Transcather closure of ASD is feasible and safe, regardless of the patient's age. A low rate of early complications was noted. Balloon sizing does not aggravate an oversizing of the device, but does not predict success. PMID- 22779024 TI - Will posttranslational modifications of brain proteins provide novel serological markers for dementias? AB - Drug development for dementias is significantly hampered by the lack of easily accessible biomarkers. Fluid biomarkers of dementias provide indications of disease stage, but have little prognostic value, cannot detect early pathological changes, and can only be measured in CSF (cerebrospinal fluid) which significantly limits their applicability. In contrast, imaging based biomarkers can provide indications of probability of disease progression, yet are limited in applicability due to cost, radiation and radio-tracers. These aspects highlight the need for other approaches to the development of biomarkers of dementia, which should focus on not only providing information about pathological changes, but also on being measured easily and reproducibly. For other diseases, focus on development of assays monitoring highly specific protease-generated cleavage fragments of proteins has provided assays, which in serum or plasma have the ability to predict early pathological changes. Proteolytic processing of brain proteins, such as tau, APP, and alpha-synuclein, is a key pathological event in dementias. Here, we speculate that aiming biomarker development for dementias at detecting small brain protein degradation fragments of generated by brain-derived proteases specifically in blood samples could lead to the development of novel markers of disease progression, stage and importantly of treatment efficacy. PMID- 22779025 TI - Glycogen synthase kinase 3: a point of integration in Alzheimer's disease and a therapeutic target? AB - Glycogen synthase kinase 3 (GSK3) has been implicated in neurological disorders; therefore, it is not surprising that there has been an increased focus towards developing therapies directed to this kinase. Unfortunately, these current therapies have not taken into consideration the physiological role of GSK3 in crucial events like synaptic plasticity. With this in mind we will discuss the relationship of synaptic plasticity with GSK3 and tau protein and their role as potential targets for the development of therapeutic strategies. Finally, we will provide perspectives in developing a cocktail therapy for Alzheimer's treatment. PMID- 22779026 TI - Microglia in Alzheimer's Disease: It's All About Context. AB - Neuroinflammation is now regarded as both an early event and prime mover in the pathobiology of Alzheimer disease (AD), a neurodegenerative disease that represents a growing public health threat. As the resident innate immune cells within the central nervous system, microglia are centrally positioned as key orchestrators of brain inflammation. It is now accepted that numerous forms of activated microglia exist. Furthermore, while some types of reactive microglia are detrimental, others can actually be beneficial. In the context of AD etiopathology, much debate surrounds whether these enigmatic cells play "good" or "bad" roles. In this article, we distill a complex clinical and experimental literature focused on the contribution of microglia to AD pathology and progression. A synthesis of the literature only seems possible when considering context- the conditions under which microglia encounter and mount immunological responses to AD pathology. In order to carry out these diverse contextual responses, a number of key receptors and signaling pathways are variously activated. It will be critically important for future studies to address molecular mediators that lead to beneficial microglial responses and therefore represent important therapeutic targets for AD. PMID- 22779027 TI - Is There Inflammatory Synergy in Type II Diabetes Mellitus and Alzheimer's Disease? AB - Metabolic dysregulation, including abnormal glucose utilization and insulin resistance or deficiency, occurs at an early stage of AD independent of type II diabetes mellitus (T2DM). Thus, AD has been considered as type 3 diabetes. T2DM is a risk factor for AD; the coexistence of these two diseases in a society with an increasing mean age is a significant issue. Recently, research has focused on shared molecular mechanisms in these two diseases with the goal of determining whether treating T2DM can lessen the severity of AD. The progress in this field lends strong support to several mechanisms that could affect these two diseases, including insulin resistance and signaling, vascular injuries, inflammation, and the receptor for advanced glycation endproducts and their ligands. In this paper, we focus on inflammation-based mechanisms in both diseases and discuss potential synergism in these mechanisms when these two diseases coexist in the same patient. PMID- 22779028 TI - The evolution of novelty in conserved gene families. AB - One of the major aims of contemporary evolutionary biology is the understanding of the current pattern of biological diversity. This involves, first, the description of character distribution at various nodes of the phylogenetic tree of life and, second, the functional explanation of such changes. The analysis of character distribution is a powerful tool at both the morphological and molecular levels. Recent high-throughput sequencing approaches provide new opportunities to study the genetic architecture of organisms at the genome-wide level. In eukaryotes, one overarching finding is the absence of simple correlations of gene count and biological complexity. Instead, the domain architecture of proteins is becoming a central focus for large-scale evolutionary innovations. Here, we review examples of the evolution of novelty in conserved gene families in insects and nematodes. We highlight how in the absence of whole-genome duplications molecular novelty can arise, how members of gene families have diversified at distinct mechanistic levels, and how gene expression can be maintained in the context of multiple innovations in regulatory mechanisms. PMID- 22779029 TI - An evaluation of the role of sensory drive in the evolution of lake Malawi cichlid fishes. AB - Although the cichlids of Lake Malawi are an important model system for the study of sensory evolution and sexual selection, the evolutionary processes linking these two phenomena remain unclear. Prior works have proposed that evolutionary divergence is driven by sensory drive, particularly as it applies to the visual system. While evidence suggests that sensory drive has played a role in the speciation of Lake Victoria cichlids, the findings from several lines of research on cichlids of Lake Malawi are not consistent with the primary tenets of this hypothesis. More specifically, three observations make the sensory drive model implausible in Malawi: (i) a lack of environmental constraint due to a broad and intense ambient light spectrum in species rich littoral habitats, (ii) pronounced variation in receiver sensory characteristics, and (iii) pronounced variability in male courtship signal characteristics. In the following work, we synthesize the results from recent studies to draw attention to the importance of sensory variation in cichlid evolution and speciation, and we suggest possible avenues of future research. PMID- 22779030 TI - Analysis of the meiotic segregation in intergeneric hybrids of tilapias. AB - Tilapia species exhibit a large ecological diversity and an important propensity to interspecific hybridisation. This has been shown in the wild and used in aquaculture. However, despite its important evolutionary implications, few studies have focused on the analysis of hybrid genomes and their meiotic segregation. Intergeneric hybrids between Oreochromis niloticus and Sarotherodon melanotheron, two species highly differentiated genetically, ecologically, and behaviourally, were produced experimentally. The meiotic segregation of these hybrids was analysed in reciprocal second generation hybrid (F2) and backcross families and compared to the meiosis of both parental species, using a panel of 30 microsatellite markers. Hybrid meioses showed segregation in accordance to Mendelian expectations, independent from sex and the direction of crosses. In addition, we observed a conservation of linkage associations between markers, which suggests a relatively similar genome structure between the two parental species and the apparent lack of postzygotic incompatibility, despite their important divergence. These results provide genomics insights into the relative ease of hybridisation within cichlid species when prezygotic barriers are disrupted. Overall our results support the hypothesis that hybridisation may have played an important role in the evolution and diversification of cichlids. PMID- 22779031 TI - Where do phosphosites come from and where do they go after gene duplication? AB - Gene duplication followed by divergence is an important mechanism that leads to molecular innovation. Divergence of paralogous genes can be achieved at functional and regulatory levels. Whereas regulatory divergence at the transcriptional level is well documented, little is known about divergence of posttranslational modifications (PTMs). Protein phosphorylation, one of the most important PTMs, has recently been shown to be an important determinant of the retention of paralogous genes. Here we test whether gains and losses of phosphorylated amino acids after gene duplication may specifically modify the regulation of these duplicated proteins. We show that when phosphosites are lost in one paralog, transitions from phosphorylated serines and threonines are significantly biased toward negatively charged amino acids, which can mimic their phosphorylated status in a constitutive manner. Our analyses support the hypothesis that divergence between paralogs can be generated by a loss of the posttranslational regulatory control on a function rather than by the complete loss of the function itself. Surprisingly, these favoured transitions cannot be reached by single mutational steps, which suggests that the function of a phosphosite needs to be completely abolished before it is restored through substitution by these phosphomimetic residues. We conclude by discussing how gene duplication could facilitate the transitions between phosphorylated and phosphomimetic amino acids. PMID- 22779032 TI - Deep phylogenetic divergence and lack of taxonomic concordance in species of astronotus (cichlidae). AB - The neotropical cichlid genus Astronotus currently comprises two valid species: A. ocellatus Agassiz, 1831 and A. crassipinnis Heckel, 1840. The diagnosis is based on color pattern and meristics counts. However, body color pattern is highly variable between regions and the meristic counts show a considerable overlap between populations differing in color patterning. They do not represent true synapomorphies that diagnose species. Purportedly the only truly diagnostic character is the presence or absence of one or more ocelli at the base of the dorsal fin, diagnosing A. ocellatus and A. crassipinnis, respectively. Using the 5' portion of the mitochondrial COI gene and EPIC nuclear markers, the validity of the dorsal ocelli as diagnostic character was tested in individuals sampled from ten localities in the Amazon basin. Analyses rejected the hypothesis that dorsal ocelli are diagnostic at the species level. However, they revealed the existence of five hypothetical, largely allopatrically distributed morphologically cryptic species. The phylogeographic structure is not necessarily surprising, since species of the genus Astronotus have sedentary and territorial habits with low dispersal potential. The distribution of these hypothetical species is coincident with patterns observed in other Amazonian aquatic fauna, suggesting the role of common historical processes in generating current biodiversity patterns. PMID- 22779033 TI - Genomic structure and evolution of multigene families: "flowers" on the human genome. AB - We report the results of an extensive investigation of genomic structures in the human genome, with a particular focus on relatively large repeats (>50 kb) in adjacent chromosomal regions. We named such structures "Flowers" because the pattern observed on dot plots resembles a flower. We detected a total of 291 Flowers in the human genome. They were predominantly located in euchromatic regions. Flowers are gene-rich compared to the average gene density of the genome. Genes involved in systems receiving environmental information, such as immunity and detoxification, were overrepresented in Flowers. Within a Flower, the mean number of duplication units was approximately four. The maximum and minimum identities between homologs in a Flower showed different distributions; the maximum identity was often concentrated to 100% identity, while the minimum identity was evenly distributed in the range of 78% to 100%. Using a gene conversion detection test, we found frequent and/or recent gene conversion events within the tested Flowers. Interestingly, many of those converted regions contained protein-coding genes. Computer simulation studies suggest that one role of such frequent gene conversions is the elongation of the life span of gene families in a Flower by the resurrection of pseudogenes. PMID- 22779034 TI - Inhibition of Bone Loss by Cissus quadrangularis in Mice: A Preliminary Report. AB - Women drastically loose bone during and after menopause leading to osteoporosis, a disease characterized by low bone mass increasing the risk of fractures with minor trauma. Existing therapies mainly reduce bone resorption, however, all existing drugs have severe side effects. Recently, the focus is to identify alternative medicines that can prevent and treat osteoporosis with minimal or no side effects. We used Cissus quadrangularis (CQ), a medicinal herb, to determine its effects on bone loss after ovariectomy in C57BL/6 mice. Two-month old mice were either sham operated or ovariectomized and fed CQ diet. After eleven weeks, mice were sacrificed and the long bones scanned using pQCT and MUCT. In the distal femoral metaphysis, femoral diaphysis, and proximal tibia, control mice had decreased cancellous and cortical bone, while CQ-fed mice showed no significant differences in the trabecular number, thickness, and connectivity density, between Sham and OVX mice, except for cortical bone mineral content in the proximal tibia. There were no changes in the bone at the tibio-fibular junction between groups. We conclude that CQ effectively inhibited bone loss in the cancellous and cortical bones of femur and proximal tibia in these mice. PMID- 22779035 TI - Clinical and economic outcomes of thyroid surgery in elderly patients: a systematic review. AB - The U.S. population is undergoing a dramatic shift in demographics, with a rise in the proportion of elderly Americans. Given an increased prevalence of thyroid disease and malignancy with age, understanding the safety of thyroid surgery in this age group is increasingly pertinent. There remains disagreement regarding the clinical outcomes of elderly patients after thyroidectomy and the applicability of single-institution cohorts to the population at large. This paper reviews the epidemiology of thyroid disease in the elderly, current surgical indications and practice patterns, and the clinical and economic outcomes of elderly patients with thyroid disease after surgical intervention. PMID- 22779036 TI - Electrochemical deposition and formation mechanism of single-crystalline cu(2)o octahedra on aluminum. AB - A simple electrochemical deposition was developed to synthesize the cuprous oxide (Cu(2)O) octahedra on aluminum foils. The average edge length of the octahedra is about 300 nm. The chemical composition of the octahedra was determined using energy dispersive X-ray spectroscopy and electron energy-loss spectroscopy. The microstructure of the octahedra was investigated using transmission electron microscopy. The formation mechanism of the octahedra is proposed. PMID- 22779037 TI - From sequencer to supercomputer: an automatic pipeline for managing and processing next generation sequencing data. AB - Next Generation Sequencing is highly resource intensive. NGS Tasks related to data processing, management and analysis require high-end computing servers or even clusters. Additionally, processing NGS experiments requires suitable storage space and significant manual interaction. At The Ohio State University's Biomedical Informatics Shared Resource, we designed and implemented a scalable architecture to address the challenges associated with the resource intensive nature of NGS secondary analysis built around Illumina Genome Analyzer II sequencers and Illumina's Gerald data processing pipeline. The software infrastructure includes a distributed computing platform consisting of a LIMS called QUEST (http://bisr.osumc.edu), an Automation Server, a computer cluster for processing NGS pipelines, and a network attached storage device expandable up to 40TB. The system has been architected to scale to multiple sequencers without requiring additional computing or labor resources. This platform provides demonstrates how to manage and automate NGS experiments in an institutional or core facility setting. PMID- 22779038 TI - Dependency Parser-based Negation Detection in Clinical Narratives. AB - Negation of clinical named entities is common in clinical documents and is a crucial factor to accurately compile patients' clinical conditions and to further support complex phenotype detection. In 2009, Mayo Clinic released the clinical Text Analysis and Knowledge Extraction System (cTAKES), which includes a negation annotator that identifies negation status of a named entity by searching for negation words within a fixed word distance. However, this negation strategy is not sophisticated enough to correctly identify complicated patterns of negation. This paper aims to investigate whether the dependency structure from the cTAKES dependency parser can improve the negation detection performance. Manually compiled negation rules, derived from dependency paths were tested. Dependency negation rules do not limit the negation scope to word distance; instead, they are based on syntactic context. We found that using a dependency-based negation proved a superior alternative to the current cTAKES negation annotator. PMID- 22779039 TI - Cohort identification for clinical research: querying federated electronic healthcare records using controlled vocabularies and semantic types. AB - In the United Kingdom (UK), local initiatives have started to federate electronic healthcare records from different primary care clinical systems, mainly for the purposes of ensuring that health care services effectively meet the needs of the population. The use of such information is being investigated for clinical research, notably in patient cohort identification and recruitment. To achieve these aims, it is essential that the information from different systems can be searched from a single interface. While interoperability is a widely researched topic, interoperable methods and data sources in primary care are largely missing. This paper describes our approach to enabling primary care data in England to be searchable on a platform developed for performing large national collaborative primary care research studies throughout the United States. PMID- 22779040 TI - Using semantic web technologies for cohort identification from electronic health records for clinical research. AB - The ability to conduct genome-wide association studies (GWAS) has enabled new exploration of how genetic variations contribute to health and disease etiology. One of the key requirements to perform GWAS is the identification of subject cohorts with accurate classification of disease phenotypes. In this work, we study how emerging Semantic Web technologies can be applied in conjunction with clinical data stored in electronic health records (EHRs) to accurately identify subjects with specific diseases for inclusion in cohort studies. In particular, we demonstrate the role of using Resource Description Framework (RDF) for representing EHR data and enabling federated querying and inferencing via standardized Web protocols for identifying subjects with Diabetes Mellitus. Our study highlights the potential of using Web-scale data federation approaches to execute complex queries. PMID- 22779042 TI - A simulation platform to examine heterogeneity influence on treatment. AB - Although a protocol aims to guide treatment management and optimize overall outcomes, the benefits and harms for each individual vary due to heterogeneity. Some protocols integrate clinical and genetic variation to provide treatment recommendation; it is not clear whether such integration is sufficient. If not, treatment outcomes may be sub-optimal for certain patient sub-populations. Unfortunately, running a clinical trial to examine such outcome responses is cost prohibitive and requires a significant amount of time to conduct the study. We propose a simulation approach to discover this knowledge from electronic medical records; a rapid method to reach this goal. We use the well-known drug warfarin as an example to examine whether patient characteristics, including race and the genes CYP2C9 and VKORC1, have been fully integrated into dosing protocols. The two genes mentioned above have been shown to be important in patient response to warfarin. PMID- 22779041 TI - Quantifying multi-ethnic representation in genetic studies of high mortality diseases. AB - Most GWASs were performed using study populations with Caucasian ethnicity or ancestry, and findings from one ethnic subpopulation might not always translate to another. We curated 4,573 genetic studies on 763 human diseases and identified 3,461 disease-susceptible SNPs with genome-wide significance; only 10% of these had been validated in at least two different ethnic populations. SNPs for autoimmune diseases demonstrated the lowest percentage of cross-ethnicity validation. We used the mortality data from the Center for Disease Control and Prevention and identified 19 diseases killing over 10,000 Americans per year that were still lacking publications of even a single cross-ethnic SNP. Fifteen of these diseases had never been studied in large GWAS in non-Caucasian populations, including chronic liver diseases and cirrhosis, leukemia, and non-Hodgkin's lymphoma. Our results demonstrate that diseases killing most Americans are still lacking genetic studies across ethnicities. PMID- 22779043 TI - Semantator: annotating clinical narratives with semantic web ontologies. AB - To facilitate clinical research, clinical data needs to be stored in a machine processable and understandable way. Manual annotating clinical data is time consuming. Automatic approaches (e.g., Natural Language Processing systems) have been adopted to convert such data into structured formats; however, the quality of such automatically extracted data may not always be satisfying. In this paper, we propose Semantator, a semi-automatic tool for document annotation with Semantic Web ontologies. With a loaded free text document and an ontology, Semantator supports the creation/deletion of ontology instances for any document fragment, linking/disconnecting instances with the properties in the ontology, and also enables automatic annotation by connecting to the NCBO annotator and cTAKES. By representing annotations in Semantic Web standards, Semantator supports reasoning based upon the underlying semantics of the owl:disjointWith and owl:equivalentClass predicates. We present discussions based on user experiences of using Semantator. PMID- 22779044 TI - A bayesian translational framework for knowledge propagation, discovery, and integration under specific contexts. AB - The immense corpus of biomedical literature existing today poses challenges in information search and integration. Many links between pieces of knowledge occur or are significant only under certain contexts-rather than under the entire corpus. This study proposes using networks of ontology concepts, linked based on their co-occurrences in annotations of abstracts of biomedical literature and descriptions of experiments, to draw conclusions based on context-specific queries and to better integrate existing knowledge. In particular, a Bayesian network framework is constructed to allow for the linking of related terms from two biomedical ontologies under the queried context concept. Edges in such a Bayesian network allow associations between biomedical concepts to be quantified and inference to be made about the existence of some concepts given prior information about others. This approach could potentially be a powerful inferential tool for context-specific queries, applicable to ontologies in other fields as well. PMID- 22779045 TI - Using SNOMED-CT to encode summary level data - a corpus analysis. AB - Extracting and encoding clinical information captured in free text with standard medical terminologies is vital to enable secondary use of electronic medical records (EMRs) for clinical decision support, improved patient safety, and clinical/translational research. A critical portion of free text is comprised of 'summary level' information in the form of problem lists, diagnoses and reasons of visit. We conducted a systematic analysis of SNOMED-CT in representing the summary level information utilizing a large collection of summary level data in the form of itemized entries. Results indicate that about 80% of the entries can be encoded with SNOMED-CT normalized phrases. When tolerating one unmapped token, 96% of the itemized entries can be encoded with SNOMED-CT concepts. The study provides a solid foundation for developing an automated system to encode summary level data using SNOMED-CT. PMID- 22779046 TI - Coanalysis of GWAS with eQTLs reveals disease-tissue associations. AB - Expression quantitative trait loci (eQTL), or genetic variants associated with changes in gene expression, have the potential to assist in interpreting results of genome-wide association studies (GWAS). eQTLs also have varying degrees of tissue specificity. By correlating the statistical significance of eQTLs mapped in various tissue types to their odds ratios reported in a large GWAS by the Wellcome Trust Case Control Consortium (WTCCC), we discovered that there is a significant association between diseases studied genetically and their relevant tissues. This suggests that eQTL data sets can be used to determine tissues that play a role in the pathogenesis of a disease, thereby highlighting these tissue types for further post-GWAS functional studies. PMID- 22779047 TI - Feasibility of pooling annotated corpora for clinical concept extraction. AB - Availability of annotated corpora has facilitated application of machine learning algorithms to concept extraction from clinical notes. However, it is expensive to prepare annotated corpora in individual institutions, and pooling of annotated corpora from other institutions is a potential solution. In this paper we investigate whether pooling of corpora from two different sources, can improve performance and portability of resultant machine learning taggers for medical problem detection. Specifically, we pool corpora from 2010 i2b2/VA NLP challenge and Mayo Clinic Rochester, to evaluate taggers for recognition of medical problems. Contrary to our expectations, pooling of corpora is found to decrease the F1-score. We examine the annotation guidelines to identify factors for incompatibility of the corpora and suggest development of a standard annotation guideline by the clinical NLP community to allow compatibility of annotated corpora. PMID- 22779048 TI - I-spline Smoothing for Calibrating Predictive Models. AB - We proposed the I-spline Smoothing approach for calibrating predictive models by solving a nonlinear monotone regression problem. We took advantage of I-spline properties to obtain globally optimal solutions while keeping the computational cost low. Numerical studies based on three data sets showed the empirical evidences of I-spline Smoothing in improving calibration (i.e.,1.6x, 1.4x, and 1.4x on the three datasets compared to the average of competitors-Binning, Platt Scaling, Isotonic Regression, Monotone Spline Smoothing, Smooth Isotonic Regression) without deterioration of discrimination. PMID- 22779049 TI - Formal concept analysis of disease similarity. AB - Previous work shows that gene associations and network properties common between pairs of diseases can provide molecular evidence of comorbidity, but relationships among diseases may extend to larger groups. Formal concept analysis allows the study of multiple diseases based on a concept lattice whose structure indicates gene set commonality. We use the concept lattice for gene associations to evaluate the complexity of the relationships among diseases, and to identify concepts whose gene sets are candidates for further functional analysis. For this, we define a heuristic on the lattice structure that allows the identification of concepts whose gene sets indicate strong relationships among the included diseases, which are distinguished from other diseases in the family. Applying this approach to a family of renal diseases we demonstrate that this approach finds gene sets that may be promising for studying common (and differing) mechanism among a family of comorbid or phenotypically related diseases. PMID- 22779050 TI - Using temporal patterns in medical records to discern adverse drug events from indications. AB - Researchers estimate that electronic health record systems record roughly 2 million ambulatory adverse drug events and that patients suffer from adverse drug events in roughly 30% of hospital stays. Some have used structured databases of patient medical records and health insurance claims recently-going beyond the current paradigm of using spontaneous reporting systems like AERS-to detect drug safety signals. However, most efforts do not use the free-text from clinical notes in monitoring for drug-safety signals. We hypothesize that drug-disease co occurrences, extracted from ontology-based annotations of the clinical notes, can be examined for statistical enrichment and used for drug safety surveillance. When analyzing such co-occurrences of drugs and diseases, one major challenge is to differentiate whether the disease in a drug-disease pair represents an indication or an adverse event. We demonstrate that it is possible to make this distinction by combining the frequency distribution of the drug, the disease, and the drug-disease pair as well as the temporal ordering of the drugs and diseases in each pair across more than one million patients. PMID- 22779051 TI - A Partitioning Based Adaptive Method for Robust Removal of Irrelevant Features from High-dimensional Biomedical Datasets. AB - We propose a novel method called Partitioning based Adaptive Irrelevant Feature Eliminator (PAIFE) for dimensionality reduction in high-dimensional biomedical datasets. PAIFE evaluates feature-target relationships over not only a whole dataset, but also the partitioned subsets and is extremely effective in identifying features whose relevancies to the target are conditional on certain other features. PAIFE adaptively employs the most appropriate feature evaluation strategy, statistical test and parameter instantiation. We envision PAIFE to be used as a third-party data pre-processing tool for dimensionality reduction of high-dimensional clinical datasets. Experiments on synthetic datasets showed that PAIFE consistently outperformed state-of-the-art feature selection methods in removing irrelevant features while retaining relevant features. Experiments on genomic and proteomic datasets demonstrated that PAIFE was able to remove significant numbers of irrelevant features in real-world biomedical datasets. Classification models constructed from the retained features either matched or improved the classification performances of the models constructed using all features. PMID- 22779052 TI - LC Data QUEST: A Technical Architecture for Community Federated Clinical Data Sharing. AB - The University of Washington Institute of Translational Health Sciences is engaged in a project, LC Data QUEST, building data sharing capacity in primary care practices serving rural and tribal populations in the Washington, Wyoming, Alaska, Montana, Idaho region to build research infrastructure. We report on the iterative process of developing the technical architecture for semantically aligning electronic health data in primary care settings across our pilot sites and tools that will facilitate linkages between the research and practice communities. Our architecture emphasizes sustainable technical solutions for addressing data extraction, alignment, quality, and metadata management. The architecture provides immediate benefits to participating partners via a clinical decision support tool and data querying functionality to support local quality improvement efforts. The FInDiT tool catalogues type, quantity, and quality of the data that are available across the LC Data QUEST data sharing architecture. These tools facilitate the bi-directional process of translational research. PMID- 22779054 TI - Analyzing patterns of drug use in clinical notes for patient safety. AB - Doctors prescribe drugs for indications that are not FDA approved. Research indicates that 21% of prescriptions filled are for off-label indications. Of those, more than 73% lack supporting scientific evidence. Traditional drug safety alerts may not cover usages that are not FDA approved. Therefore, analyzing patterns of off-label drug usage in the clinical setting is an important step toward reducing the incidence of adverse events and for improving patient safety. We applied term extraction tools on the clinical notes of a million patients to compile a database of statistically significant patterns of drug use. We validated some of the usage patterns learned from the data against sources of known on-label and off-label use. Given our ability to quantify adverse event risks using the clinical notes, this will enable us to address patient safety because we can now rank-order off-label drug use and prioritize the search for their adverse event profiles. PMID- 22779053 TI - Integrative analysis of common neurodegenerative diseases using gene association, interaction networks and mRNA expression data. AB - Alzheimer's and Parkinson's diseases (AD and PD) are two common neurodegenerative diseases primarily affecting memory and motor functions, respectively. In this study, we integrated data from various sources, and took a systems-biology approach to compare and contrast the molecular and network based dysregulation associated with AD and PD and we integrated these data with known pathways of drug treatment. First, we identified genes that exhibit consistent prior evidence of association with each disease. Then, we extracted disease-specific sub networks from a human interactome database using associated genes as seeds. To rank the sub-networks we used existing gene expression data from cases and controls. Comparison of resulting disease-associated genes and networks revealed significant overlap between AD and PD. In addition, the identified sub-networks correlated with known drug interdiction pathways, and suggested new potential targets for intervention. PMID- 22779055 TI - EliXR-TIME: A Temporal Knowledge Representation for Clinical Research Eligibility Criteria. AB - Effective clinical text processing requires accurate extraction and representation of temporal expressions. Multiple temporal information extraction models were developed but a similar need for extracting temporal expressions in eligibility criteria (e.g., for eligibility determination) remains. We identified the temporal knowledge representation requirements of eligibility criteria by reviewing 100 temporal criteria. We developed EliXR-TIME, a frame-based representation designed to support semantic annotation for temporal expressions in eligibility criteria by reusing applicable classes from well-known clinical temporal knowledge representations. We used EliXR-TIME to analyze a training set of 50 new temporal eligibility criteria. We evaluated EliXR-TIME using an additional random sample of 20 eligibility criteria with temporal expressions that have no overlap with the training data, yielding 92.7% (76 / 82) inter-coder agreement on sentence chunking and 72% (72 / 100) agreement on semantic annotation. We conclude that this knowledge representation can facilitate semantic annotation of the temporal expressions in eligibility criteria. PMID- 22779056 TI - Integrating genome and functional genomics data to reveal perturbed signaling pathways in ovarian cancers. AB - Cancers are genetic diseases, driven by somatic mutations that perturb cellular signaling systems. In this study, we aim to reveal the signal transduction pathways that are perturbed by mutations in ovarian cancer. Our approach searches for genetic mutations that lead to a common cellular response, e.g., differential expression of a set of functional related genes. To this end, we first developed a knowledge mining approach to identify functional expression modules; we then developed a graph-based data mining approach to identify mutations that are highly related to the functional modules, as a means to re-constitute signal pathways. Our results indicate that unification of knowledge mining with data mining significantly enhance identification of potential signaling pathways in ovarian cancers. PMID- 22779057 TI - Context-specific ontology integration: a bayesian approach. AB - We introduce a principled computational framework and methodology for automated discovery of context-specific functional links between ontologies. Our model leverages over disparate free-text literature resources to score the model of dependency linking two terms under a context against their model of independence. We identify linked terms as those having a significant bayes factor (p < 0.01). To scale our algorithm over massive ontologies, we propose a heuristic pruning technique as an efficient algorithm for inferring such links.We have applied this method to translationalize Gene Ontology to all other ontologies available at National Center of Biomedical Ontology (NCBO) BioPortal under the context of Human Disease ontology. Our results show that in addition to broadening the scope of hypothesis for researchers, our work can potentially be used to explore continuum of relationships among ontologies to guide various biological experiments. PMID- 22779058 TI - A selective voting convex-hull ensemble procedure for personalized medicine. AB - Genes work in concert as a system as opposed to independent entities and mediate disease states. There has been considerable interest in understanding variations in molecular signatures between normal and disease states. However, a majority of techniques implicitly assume homogeneity between samples within a given group and use a fixed set of genes in discerning the groups. The proposed study overcomes these caveats by using a selective-voting convex-hull ensemble procedure that accommodates molecular heterogeneity within and between groups. The significance of the study is its potential to selectively retrieve sample-specific ensemble sets and investigate variations in the networks corresponding to the ensemble set across these samples. These characteristics fit well within the scope of personalized medicine and comparative effectiveness research that emphasize on patient-tailored interventions. While the results are demonstrated on colon cancer gene expression profiles the approach as such is generic and can be readily extended to other settings. PMID- 22779059 TI - An automated bayesian framework for integrative gene expression analysis and predictive medicine. AB - MOTIVATION: This work constructs a closed loop Bayesian Network framework for predictive medicine via integrative analysis of publicly available gene expression findings pertaining to various diseases. RESULTS: An automated pipeline was successfully constructed. Integrative models were made based on gene expression data obtained from GEO experiments relating to four different diseases using Bayesian statistical methods. Many of these models demonstrated a high level of accuracy and predictive ability. The approach described in this paper can be applied to any complex disorder and can include any number and type of genome-scale studies. PMID- 22779060 TI - Towards an Oncology Database (ONCOD) Using a Warehousing Approach. AB - Here we report a model data mart developed upon a warehousing system focusing on oncology data to explore optimized system architecture to support enhanced data integration and application capacity. PMID- 22779061 TI - Identifying common genes and networks in multi-organ fibrosis. AB - Fibroproliferative diseases of organs are poorly understood and generally lack effective anti-fibrotic treatments. Our goal was to identify the key regulatory factors in pathologic fibrosis, common between organ-based fibrotic disease. We analyzed 9 microarray datasets publicly available in the GEO datasets from lung, heart, liver and kidney fibrotic disease tissue (489 microarrays total, disease and control). We identified a set of 90 genes differentially expressed in at least five microarray datasets. We used IPA and DAVID analysis to identify gene networks and their molecular functions. A mutual information based network work activity analysis showed that a connective tissue disorders network was the most active for all types of fibrosis included in this analysis. CONCLUSION: Our analysis indicates that despite different disease manifestation, organ fibrosis share a specific set of genes suggesting the potential for a common origin. PMID- 22779062 TI - Deep circumflex iliac artery pseudoaneurysm as a complication of paracentesis. AB - We report a case of a pseudoaneurysm arising from the deep circumflex iliac artery, in an end-stage renal disease patient with gross ascitis, presenting with an anterior abdominal wall hematoma following paracentesis. Duplex Doppler sonography confirmed the presence of the pseudoaneurysm and multidetector computed tomography angiography delineated the detailed arterial anatomy. PMID- 22779063 TI - Asymptomatic thymic cyst appearing in the neck on valsalva: unusual presentation of a rare disease. AB - Thymic cysts are usually diagnosed accidentally during radiological evaluation of the chest for unrelated conditions. Symptoms appear late when the mass compresses on adjoining tissues. We report an unusual case of asymptomatic mediastinal thymic cyst which was seen in the neck whenever the patient was asked to perform Valsalva maneuver. This case is being reported for the unusual clinical presentation of a rare disease. The role of imaging in the diagnosis and common differential diagnoses are also discussed. PMID- 22779064 TI - Trueness assessment for serum glucose measurement using commercial systems through the preparation of commutable reference materials. AB - BACKGROUND: Commutable reference materials (RMs) are suitable for end-users for evaluating the metrological traceability of values obtained using routine measurement systems. We assessed the performance of 6 routine measurement systems with validated secondary RMs. METHODS: We tested the homogeneity, stability, and commutability of 5 minimally processed human serum pools according to the standard guidelines. The serum pools were assigned values as per the reference procedure of the United States Centers for Disease Control and were used to evaluate the trueness of results from 6 commercial measurement systems based on enzymatic methods: 3 glucose oxidase (GOD) and 3 hexokinase (HK) methods. RESULTS: The prepared RMs were validated to be sufficiently homogenous, stable, and commutable with the patient samples. Method bias varied for different systems: GOD01, -0.17 to 2.88%; GOD02, 1.66 to 4.58%; GOD03, -0.17 to 3.14%; HK01, -3.48 to -0.85%; HK02, -3.83 to -0.11%, and HK03, -1.82 to -0.27%. CONCLUSIONS: We observed that the prepared serum glucose RMs were qualified for trueness assessment. Most of the measurement systems met the minimal quality specifications. PMID- 22779065 TI - Influence of a regular, standardized meal on clinical chemistry analytes. AB - BACKGROUND: Preanalytical variability, including biological variability and patient preparation, is an important source of variability in laboratory testing. In this study, we assessed whether a regular light meal might bias the results of routine clinical chemistry testing. METHODS: We studied 17 healthy volunteers who consumed light meals containing a standardized amount of carbohydrates, proteins, and lipids. We collected blood for routine clinical chemistry tests before the meal and 1, 2, and 4 hr thereafter. RESULTS: One hour after the meal, triglycerides (TG), albumin (ALB), uric acid (UA), phosphatase (ALP), Ca, Fe, and Na levels significantly increased, whereas blood urea nitrogen (BUN) and P levels decreased. TG, ALB, Ca, Na, P, and total protein (TP) levels varied significantly. Two hours after the meal, TG, ALB, Ca, Fe, and Na levels remained significantly high, whereas BUN, P, UA, and total bilirubin (BT) levels decreased. Clinically significant variations were recorded for TG, ALB, ALT, Ca, Fe, Na, P, BT, and direct bilirubin (BD) levels. Four hours after the meal, TG, ALB, Ca, Fe, Na, lactate dehydrogenase (LDH), P, Mg, and K levels significantly increased, whereas UA and BT levels decreased. Clinically significant variations were observed for TG, ALB, ALT, Ca, Na, Mg, K, C-reactive protein (CRP), AST, UA, and BT levels. CONCLUSIONS: A significant variation in the clinical chemistry parameters after a regular meal shows that fasting time needs to be carefully considered when performing tests to prevent spurious results and reduce laboratory errors, especially in an emergency setting. PMID- 22779066 TI - Evaluation of peptide nucleic acid probe-based real-time PCR for detection of Mycobacterium tuberculosis complex and nontuberculous mycobacteria in respiratory specimens. AB - BACKGROUND: A peptide nucleic acid (PNA) probe-based real-time PCR (PNAqPCRTM TB/NTM detection kit; PANAGENE, Korea) assay has been recently developed for the simultaneous detection of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM) in clinical specimens. The study was aimed at evaluation of the performance of PNA probe-based real-time PCR in respiratory specimens. METHODS: To evaluate potential cross-reactivity, the extracted DNA specimens from Mycobacterium species and non-mycobacterial species were tested using PNA probe-based real-time PCR assay. A total of 531 respiratory specimens (482 sputum specimens and 49 bronchoalveolar washing fluid specimens) were collected from 230 patients in July and August, 2011. All specimens were analyzed for the detection of mycobacteria by direct smear examination, mycobacterial culture, and PNA probe-based real-time PCR assay. RESULTS: In cross-reactivity tests, no false-positive or false-negative results were evident. When the culture method was used as the gold standard test for comparison, PNA probe-based real time PCR assay for detection of MTBC had a sensitivity and specificity of 96.7% (58/60) and 99.6% (469/471), respectively. Assuming the combination of culture and clinical diagnosis as the standard, the sensitivity and specificity of the new real-time PCR assay for detection of MTBC were 90.6% (58/64) and 99.6% (465/467), respectively. The new real-time PCR for the detection of NTM had a sensitivity and specificity of 69.0% (29/42) and 100% (489/489), respectively. CONCLUSIONS: The new real-time PCR assay may be useful for the detection of MTBC in respiratory specimens and for discrimination of NTM from MTBC. PMID- 22779067 TI - Rapid diagnosis of tuberculosis and multidrug resistance using a MGIT 960 system. AB - BACKGROUND: The purpose of this study was to compare the turnaround time for liquid culturing and primary anti-tuberculous drug susceptibility testing (DST) performed using the mycobacteria growth indicator tube (MGIT) 960 system (Becton Dickinson, USA) with that for conventional culturing and DST (by the absolute concentration method) performed using solid culture medium and to determine the concordance rates of DST results obtained using these 2 methods. METHODS: In this retrospective study, we compared the turnaround times from receiving the request for mycobacterial culture to reporting the DST results before and after the introduction of the MGIT 960 system. Further, we determined the concordance between DST results for isoniazid and rifampin for Mycobacterium tuberculosis isolates obtained using the MGIT 960 system and the absolute concentration method, which was conducted at the Korean Institute of Tuberculosis. RESULTS: The overall turnaround time for mycobacterial culturing and DST was 27 days for liquid culturing and DST using the MGIT 960 system versus approximately 70 days for culturing on solid medium and DST with the absolute concentration method (P<0.001). There was a good concordance between findings of DST obtained with the 2 methods (97.2%, kappa coefficient=0.855 for rifampin; and 95.6%, kappa coefficient=0.864 for isoniazid), for 1,083 clinical isolates. CONCLUSIONS: The automated MGIT 960 system for culturing and DST of M. tuberculosis was successfully introduced in a hospital laboratory setting in Korea with significant shortening of the turnaround time. PMID- 22779068 TI - Characterization of carbapenemase genes in Enterobacteriaceae species exhibiting decreased susceptibility to carbapenems in a university hospital in Chongqing, China. AB - BACKGROUND: Our study was to investigate the prevalence of carbapenemase genes in strains of Enterobacteriaceae species exhibiting decreased susceptibility to carbapenems in our hospital. METHODS: The carbapenemase producing Enterobacteriaceae species were confirmed by modified Hodge test (MHT) and EDTA disc synergy test which indicating the production of class B carbapenemases. PCR and sequencing analysis were used to identify the drug-resistant genes. DNA fingerprinting based on enterobacterial repetitive intergenic consensus (ERIC) PCR was applied to investigate the homology of Enterobacteriaceae species. RESULTS: From a collection of 1,472 Enterobacteriaceae species, 18 isolates with decreased susceptibility to carbapenem treatment were identified and 9 of which were positive by MHT, and 6 of which produced class B carbapenemases. PCR and sequencing analysis of the 18 isolates revealed 4 different carbapenemase genes (bla(IMP-8), bla(oxa-1), bla(IMP-26), and bla(oxa-47)) in 10 isolates, with the bla(IMP-8) and bla(oxa-1) genes being the most common (60-70% prevalence). ERIC PCR showed 5, 2, and 2 unique genotypes for Enterobacter cloacae, Escherichia coli, and Klebsiella pneumoniae, respectively. Three E. coli strains isolated from different patients from the urologic surgery department exhibited the same DNA banding pattern, suggesting a possible clonal dissemination. Majority (17/18) of the carbapenem-unsusceptible Enterobacteriaceae species isolates was obtained from the surgery department of our hospital. CONCLUSIONS: The main carbapenemase genes of Enterobacteriaceae species in our hospital were bla(IMP-8) and bla(oxa 1). Prevalence of carbapenem resistance may be existed in surgery department and infection control should be taken for preventing further dissemination of drug resistant strains. PMID- 22779069 TI - Erythrocyte binding preference of human pandemic influenza virus a and its effect on antibody response detection. AB - BACKGROUND: Validation of hemagglutination inhibition (HI) assays is important for evaluating antibody responses to influenza virus, and selection of erythrocytes for use in these assays is important. This study aimed to determine the correlation between receptor binding specificity and effectiveness of the HI assay for detecting antibody response to pandemic influenza H1N1 (pH1N1) virus. METHODS: Hemagglutination (HA) tests were performed using erythrocytes from 6 species. Subsequently, 8 hemagglutinating units of pH1N1 from each species were titrated by real-time reverse transcription-PCR. To investigate the effect of erythrocyte binding preference on HI antibody titers, comparisons of HI with microneutralization (MN) assays were performed. RESULTS: Goose erythrocytes showed most specific binding with pH1N1, while HA titers using human erythrocytes were comparable to those using turkey erythrocytes. The erythrocyte binding efficiency was shown to have an impact on antibody detection. Comparing MN titers, HI titers using turkey erythrocytes yielded the most accurate results, while those using goose erythrocytes produced the highest geometric mean titer. Human blood group O erythrocytes lacking a specific antibody yielded results most comparable to those obtained using turkey erythrocytes. Further, pre-existing antibody to pH1N1 and different erythrocyte species can distort HI assay results. CONCLUSIONS: HI assay, using turkey and human erythrocytes, yielded the most comparable and applicable results for pH1N1 than those by MN assay, and using goose erythrocytes may lead to overestimated titers. Selection of appropriate erythrocyte species for HI assay allows construction of a more reliable database, which is essential for further investigations and control of virus epidemics. PMID- 22779070 TI - Role of plasma exchange in ABO-incompatible kidney transplantation. AB - BACKGROUND: In the past, ABO incompatibility was an absolute contraindication for solid organ transplantation. However, multiple recent trials have suggested strategies for overcoming the reactions between graft antigens and recipient antibodies that cause graft rejection. In this study, we determined the usefulness of plasma exchange (PE) for removing anti-A/B antibodies that cause hyperacute/acute humoral graft rejection in patients undergoing ABO-incompatible kidney transplantation. METHODS: In our study, 12 patients underwent ABO incompatible kidney transplantation. All recipients received pre-transplantation conditioning by PE or intravenous immunoglobulin (IVIG) administration. After pre transplantation conditioning, anti-A/B antibody titers were evaluated, and transplantation was performed when the titer was below 1:8. To assess the transplantation outcome, anti-A/B antibody titers, creatinine level, estimated glomerular filtration rate (eGFR), and proteinuria levels were measured. RESULTS: Anti-A/B antibody titers were below 1:8 in all patients at the time of transplantation. eGFR measured on post-transplant day 14 showed that 10 patients had immediate recovery of graft function, while 2 patients had slow recovery of graft function. Short-term outcomes of ABO-incompatible kidney transplantation (measured as creatinine levels) after reducing anti-A/B antibody titers were similar to those of ABO-compatible kidney transplantation. After transplantation, the anti-A/B antibody titers were below 1:8 in 7 patients, but the remaining 5 patients required post-transplantation PE and IVIG treatment to prevent antigen antibody reactions. CONCLUSIONS: With the increasing demand for kidney donations, interest in overcoming the ABO incompatibility barrier has increased. PE may be an important breakthrough in increasing the availability of kidneys for transplantation. PMID- 22779071 TI - MYC rearrangement involving a novel non-immunoglobulin chromosomal locus in precursor B-cell acute lymphoblastic leukemia. AB - MYC rearrangement, a characteristic cytogenetic abnormality of Burkitt lymphoma and several subsets of other mature B-cell neoplasms, typically involves an immunoglobulin gene partner. Herein, we describe a case of precursor B-cell lymphoblastic leukemia harboring a MYC rearrangement with a novel non immunoglobulin partner locus. The patient was a 4-yr-old Korean boy with ALL of the precursor B-cell immunophenotype. At the time of the second relapse, cytogenetic analyses revealed t(4;8)(q31.1;q24.1) as a clonal evolution. The MYC rearrangement was confirmed by FISH analysis. He died 3 months after the second relapse without achieving complete remission. To our knowledge, this is the first report of a case of MYC rearrangement with a non-immunoglobulin partner in precursor B-cell lymphoblastic leukemia. PMID- 22779072 TI - A case of near-triploidy in myelodysplastic syndrome with del(5q) combined with del(1p) and del(13q). AB - Numerical and structural chromosomal abnormalities are common in hematological malignancies. Near-triploidy (58-80 chromosomes) is a numerical abnormality observed in 3% of adult cases of acute lymphoblastic leukemia. Near-triploidy is rare in myeloid lineage hematologic malignancies and compared to near-triploidy in lymphoid malignancies, near-triploidy in myeloid malignancies is associated with poor outcomes. Few studies on near-triploidy in myelodysplastic syndrome (MDS) have been reported, and the clinicopathologic significance of this condition is still unclear. Here, we report a novel case of MDS with near triploidy and multiple structural chromosomal abnormalities: del(5q) combined with del(1p) and del(13q). These abnormalities were detected by cytogenetic analysis with array comparative genomic hybridization (CGH). Our results suggest that array CGH can be a useful tool for detecting chromosomal abnormalities in patients with MDS. PMID- 22779073 TI - Lung infection caused by Mycobacterium riyadhense confused with Mycobacterium tuberculosis: the first case in Korea. AB - A slowly growing, non-chromogenic mycobacterial strain was isolated from sputum and bronchial lavage fluid samples of a patient presenting with productive cough, blood-tinged sputum, low-grade fever, and weakness. A positive acid-fast bacilli sputum smear result prompted the initiation of an anti-tuberculosis regimen. Multiplex real-time PCR showed a negative result for Mycobacterium tuberculosis complex and a positive result for nontuberculous mycobacteria. The DNA chip test confirmed this organism as a member of the genus Mycobacterium, but could not specify the species. Interestingly, the mycolic acid patterns obtained by HPLC nearly overlapped with those of M. simulans. The sequences of the Mycobacterium 16S rRNA gene and 16S-23S internal transcribed spacer region were unique and were found to have 100% similarity with those of M. riyadhense. After a review of the literature, we report this case as the first Korean case of M. riyadhense lung infection. PMID- 22779074 TI - Anaphylactic transfusion reaction in a patient with anhaptoglobinemia: the first case in Korea. AB - Anaphylactic transfusion reactions are rare complications of blood transfusions. Anhaptoglobinemia, a condition that has high incidence in Asia, can cause allergic transfusion reactions or anaphylaxis in severe cases. A 50-yr-old Korean woman was diagnosed with relapsed acute promyelocytic leukemia. She developed thrombocytopenia during chemotherapy and an anaphylactic transfusion reaction on the 4th and 5th platelet transfusions immediately after the transfusion of the platelet concentrates was initiated. Blood analysis showed no detectable serum haptoglobin. We examined her genetic phenotype and detected anhaptoglobinemia, which occurs because of an allelic deletion in the Hp gene cluster. The presence of an antibody against haptoglobin was detected by performing ELISA. To prevent anaphylactic reactions, apheresis platelets were transfused after washing. Consequently, anaphylactic transfusion reactions did not develop. Here, we report the first case of anhaptoglobinemia causing anaphylactic transfusion reaction in Korea. PMID- 22779075 TI - Ring chromosome 5 in acute myeloid leukemia defined by whole-genome single nucleotide polymorphism array. AB - Chromosomes forming a corresponding ring cannot be clearly defined by conventional cytogenetics or FISH. Karyotypic analyses using whole-genome single nucleotide polymorphism arrays (SNP-A) may result in the identification of previously cryptic lesions and allow for more precise definition of breakpoints. We describe a case of AML with metaphase cells bearing -5, del(11)(q22), and +r. With SNP-A, a 5p-terminal deletion (11 megabases [Mb]), a 5q-terminal deletion (27 Mb), an 11q-interstitial deletion (29 Mb), and a 21q gain (3 Mb) were identified. Therefore, the G-banded karyotype was revised as 46, XY, r(5)(p15. 2q33.2), del(11)(q14.1q23.2), dup(21)(q22.13q22.2)[18]/46,XY[2]. SNP-A could be a powerful tool for characterizing ring chromosomes in which the involved chromosomes or bands cannot be precisely identified by conventional cytogenetics or FISH. PMID- 22779076 TI - Identification of SLC26A3 mutations in a Korean patient with congenital chloride diarrhea. AB - Congenital chloride diarrhea (CLD) is an autosomal recessive disorder with the hallmark of persistent watery Cl(-)-rich diarrhea from birth. Mutations in the solute carrier family 26, member 3 (SLC26A3) gene, which encodes a coupled Cl( )/HCO(3)(-) exchanger in the ileum and colon, are known to cause CLD. Although there are a few reports of CLD patients in Korea, none of these had been confirmed by genetic analysis. Here, we describe the case of a Korean infant with clinical features of CLD. Using direct sequencing analysis, we identified 2 sequence variants: a missense variant of unknown significance (c.525G>C; p.Arg175 Ser) and a splicing mutation (c.2063-1G>T) in the SLC26A3 gene; these had been inherited from the father and mother, respectively. Whilst CLD is rare, its main symptom, diarrhea, is very common in infants. Hence, the diagnosis of CLD can prove difficult. Mutational analysis of the SLC26A3 gene should be considered as a viable method to confirm a diagnosis of CLD in Korean infants with persistent diarrhea. PMID- 22779077 TI - Diagnostic usefulness of genomic breakpoint analysis of various gene rearrangements in acute leukemias: a perspective of long distance- or long distance inverse-PCR-based approaches. PMID- 22779078 TI - Use of imaging multivariate analysis to improve biochemical and anatomical discrimination in desorption electrospray ionisation mass spectrometry imaging. AB - Desorption electrospray ionisation (DESI) mass spectrometry images usually contain a large amount of information that can be difficult to interpret in an objective manner. We explore the use of imaging multivariate analysis (MVA) on DESI images of protein spots and rat brain sections to automatically assign peaks and improve discrimination of spatially important features. DESI parameters were optimised on an ion trap mass spectrometer for (a) consistent imaging of dried single and mixture spots of insulin, myoglobin and BSA from a Permanox slide, and (b) to produce a MS image of rat brain coronal section at 100 MUm resolution. Multivariate curve resolution (MCR), an imaging MVA technique was applied to these images after appropriate data binning. MCR analysis on DESI images of protein mixture spots allowed the multiply charged peaks of a number of proteins to be distinctly separated. Application of MCR to a DESI image of a rat brain coronal section deconvoluted the image into components that showed biologically important features. Further application of MCR to a subsection of the image produced a component that clearly separated out the substantia nigra region, which allowed us to produce a biochemical anatomy for this area of the brain. We have demonstrated the ability of imaging MVA to automatically and objectively analyse DESI images of standardised and complex biological samples, and have shown its capacity for detailed spatial profiling of biomolecules in specific morphological regions. We propose the routine use of this technique for future DESI imaging experiments. PMID- 22779079 TI - The asymmetric synthesis of CF3- or -CF2-substituted tetrahydroquinolines by employing a chiral phosphoric acid as catalyst. AB - CF(3)- or -CF(2)-containing tetrahydroquinolines have been asymmetrically synthesized from the reaction of fluorinated N-arylimines with benzyl N vinylcarbamate in the presence of a chiral phosphoric acid. PMID- 22779080 TI - Immobilization of engineered arginase on gold-carbon nanotubes. AB - It is demonstrated that engineered arginase with a single protruded site of cysteine deliberately placed away from its active centre by site-directed mutagenesis can facilitate its attachment on a gold-nanoparticle surface with atomic precision, resulting in no apparent loss in enzymatic activity. PMID- 22779081 TI - A pro-inflammatory profile of endothelial cell in Lonomia obliqua envenomation. AB - Lonomia obliqua envenomation is characterized by intense local inflammatory reaction, which, dependent on the severity of the case, is followed by severe clinical manifestations related to hemorrhagic disorders that can lead to fatal outcome. These effects were imputed to several toxins present in L. obliqua venom, which are responsible for procoagulant, anticoagulant as well as antithrombotic activities, being also able to interfere with vascular cells functions. In this work, the intravital microscopy analysis show that after administration of low doses of L. obliqua venom (1-3 MUg/ml) on hamster cheek pouch, there was no alterations neither on arterioles or venules caliber nor in the vascular permeability up to 30 min. However, after 10 min in contact with venom occurred a clear activation in the vascular bed, characterized by an increase in leukocyte rolling and adhesion on endothelium of hamster cheek pouch venules. A confocal analysis of vascular beds, confirmed these results showing an increase in endothelial E-selectin and VCAM-1 expression. The effects of L. obliqua venom on human endothelial cell (EC) in vitro were also investigated. The treatment of EC with venom (1-3 MUg/ml) did not affect cell viability. However, at concentrations as low as 3 MUg/ml of L. obliqua venom modifies actin cytoskeleton dynamics, and increases focal adhesion contacts, inducing stress fiber formation, focal adhesion kinase (FAK) phosphorylation and its subsequent association to actin. These effects are followed by the activation of NF-kappaB pathway, a critical signaling in several events associated to vascular inflammation. Accordingly, L. obliqua venom leads to a significant increase in COX-2, NOS-2, HO-1, MMP-2 and MMP-9 expression. Taken together the data show that, even at low concentrations, L. obliqua venom can activate endothelial cells, which assume a pro-inflammatory profile, contributing for local effects and probably also for systemic disturbances due to its ability to modulate the properties of the vascular system. PMID- 22779082 TI - [Modern wound dressings]. PMID- 22779083 TI - Hope for 'NutriChip' to reveal potentially anti-inflammatory foods. PMID- 22779084 TI - Bullseye: successful determination of insulin in vitreous humor by LC-MS/MS. PMID- 22779085 TI - Nicotine, cigarette smoking and cardiac arrhythmia: an overview. AB - Tobacco smoke is the single most important modifiable risk factor for coronary diseases and the leading preventable cause of death in the US. While the effect of cigarette smoking on the progression of atherosclerotic diseases is established and well studied, the role of cigarette smoking on cardiac arrhythmia is less clearly defined. In fact the pathophysiological mechanism of cigarette smoking-induced cardiac arrhythmia is very likely a complex one where the pro fibrotic effect of nicotine on myocardial tissue with consequent increased susceptibility to catecholamine might play a role. Moreover, other constituents of cigarette smoking, such as carbon monoxide and oxidative stress, are likely to contribute to the generation of arrhythmias. Finally, cigarette smoking may induce coronary artery disease and chronic obstructive pulmonary disease, which also might cause arrhythmia independently. The objective of this paper is to summarize the published studies relating to cardiac arrhythmia induced by cigarette smoking, and to identify a pathophysiological mechanism by which cigarette smoking might induce cardiac arrhythmia. PMID- 22779086 TI - Long-term beta blockers for stable angina: systematic review and meta-analysis. AB - OBJECTIVES: To assess the effects of long-term beta blockers in patients with stable angina. METHODS: We reviewed the literature up to June 2010 from CENTRAL, MEDLINE, EMBASE, CBM, and CNKI for randomized controlled trials. The appropriate data were meta-analysed using Revman 5.0. RESULTS: Twenty-six trials including 6108 patients were identified. The treatment with beta blockers has significantly decreased all-cause mortality when compared with no control (OR 0.40, 95% CI 0.20 to 0.79), but has had no statistically differences when compared with placebo (OR 0.92, 95% CI 0.62 to 1.38) and with calcium-channel blocker (CCB) (OR0.84, 95% CI 0.49 to 1.44). This was similar in patients with fatal and non-fatal acute myocardial infarction when compared with placebo (OR 0.82, 95% CI 0.57 to 1.17) or CCB (OR 1.08, 95% CI 0.71 to 1.66); on revascularization and quality of life. The beta blockers reduced the incident of unstable angina compared to no treatment (OR 0.14, 95% CI0.07 to 0.29), but increased unstable angina compared to placebo (OR 3.32, 95% CI 1.50 to 7.36). There was a significant reduction of nitrate consumption when beta blockers were compared with CCBs (OR 1.18, 95% CI 1.54 to 0.82),but not with placebo and trimetazidine. There was no significant difference in angina attack between each group. Side effects in beta blocker were similar with ones in controls. CONCLUSIONS: Beta blockers may decrease the death and unstable angina when compared with no treatment, but no more effective than other anti-anginal agents on prophylaxis of myocardial ischaemia in stable angina patients. PMID- 22779087 TI - US Supreme Court makes historic health ruling. PMID- 22779088 TI - Jim Kim takes the helm at the World Bank. PMID- 22779089 TI - Drug cheating at the Olympics: who, what, and why? PMID- 22779091 TI - Ventricular assist device patients on the horizon of cardiovascular prevention and rehabilitation. Can we convert challenges into opportunities? PMID- 22779090 TI - Role of the pituitary-adrenal axis in granulocyte-colony stimulating factor induced neuroprotection against hypoxia-ischemia in neonatal rats. AB - Several reports indicate that the activity of the hypothalamic-pituitary-adrenal axis (HPA) is increased after a brain insult and that its down-regulation can improve detrimental outcomes associated with ischemic brain injuries.Granulocyte colony stimulating factor (G-CSF) is a neuroprotective drug shown in the naive rat to regulate hormones of the HPA axis. In this study we investigate whether G CSF confers its neuroprotective properties by influencing the HPA response after neonatal hypoxia-ischemia (HI). Following the Rice-Vannucci model, seven day old rats (P7)were subjected to unilateral carotid ligation followed by 2.5 h of hypoxia. To test our hypothesis,metyrapone was administered to inhibit the release of rodent specific glucocorticoid, corticosterone, at the adrenal level. Dexamethasone, a synthetic glucocorticoid, was administered to agonize the effects of corticosterone.Our results show that both G-CSF and metyrapone significantly reduced infarct volume while dexamethasone treatment did not reduce infarct size even when combined with G-CSF. The protective effects of G-CSF do not include blood brain barrier preservation as suggested by the brain edema results. G-CSF did not affect the pituitary released adrenocorticotropic hormone (ACTH) levels in the blood plasma at 4 h, but suppressed the increase of corticosterone in the blood. The administration of G-CSF and metyrapone increased weight gain, and significantly reduced the Bax/Bcl-2 ratio in the brain while dexamethasone reversed the effects of G-CSF. The combination of G-CSF and metyrapone significantly decreased caspase-3 protein levels in the brain, and the effect was antagonized by dexamethasone.We report that G-CSF is neuroprotective in neonatal HI by reducing infarct volume, by suppressing the HI-induced increase of the Bax/Bcl-2 ratio, and by decreasing corticosterone in the blood. Metyrapone was able to confer similar neuroprotection as G-CSF while dexamethasone reversed the effects of G-CSF. In conclusion, we show that decreasing HPA axis activity is neuroprotective after neonatal HI, which can be conferred by administering G-CSF. PMID- 22779092 TI - Participating in cardiac rehabilitation: a systematic review and meta-synthesis of qualitative data. AB - BACKGROUND: Participation in cardiac rehabilitation (CR) benefits patients with coronary heart disease (CHD), yet worldwide only some 15-30% of those eligible attend. To improve understanding of the reasons for poor participation we undertook a systematic review and meta-synthesis of the qualitative literature. METHODS: Qualitative studies identifying patient barriers and enablers to attendance at CR were identified by searching multiple electronic databases, reference lists, relevant conference lists, grey literature, and keyword searching of the Internet (1990-2010). Studies were selected if they included patients with CHD and reviewed experience or understanding about CR. Meta synthesis was used to review the papers and to synthesize the data. RESULTS: From 1165 papers, 34 unique studies were included after screening. These included 1213 patients from eight countries. Study methodology included interviews (n = 25), focus groups (n = 5), and mixed-methods (n = 4). Key reasons for not attending CR were physical barriers, such as lack of transport, or financial cost, and personal barriers, such as embarrassment about participation, or misunderstanding the reasons for onset of CHD or the purpose of CR. CONCLUSIONS: There is a vast amount of qualitative research which investigates patients' reasons for non attendance at CR. Key issues include system-level and patient-level barriers, which are potentially modifiable. Future research would best be directed at investigating strategies to overcome these barriers. PMID- 22779093 TI - Dirt, dirt everywhere: nary a drop to clean. PMID- 22779094 TI - Psoriasis of the lips: an uncommon presentation of a common dermatologic condition. PMID- 22779095 TI - Burning mouth syndrome. PMID- 22779096 TI - A comparison of the tolerability of adapalene 0.1% cream and adapalene 0.1% lotion in healthy individuals. AB - Two separate single-center, randomized, evaluator-blinded, bilateral (split-face) comparison studies compared the tolerability of adapalene 0.1% cream with adapalene 0.1% lotion in individuals with healthy skin treated once per day for 3 weeks. At each visit, the participants were graded on erythema, scaling, dryness, and stinging/burning (scale: 0 = none to 3 = severe). On the final study visit, the participants completed a Cosmetic Acceptability Questionnaire. Adverse events were recorded at each study visit. A total of 144 participants were enrolled and 130 completed the studies (study 1, n = 66; study 2, n = 64). The lotion formulation was non-inferior to the cream for the success rates and tolerability assessments in both studies. The frequency distributions of worst scores of either 0 (none) or 1 (mild) (study 1; study 2) for adapalene lotion were erythema (98.5%; 40.7%), scaling (100%; 73.5%), dryness (100%; 68.8%), and stinging/burning (98.5%; 100%). The most common treatment-related adverse event was dryness (study 1, cream 2.7% [2 of 75] and lotion 4.0% [3/75]); study 2, cream 2.9% [2 of 69] and lotion 4.3% [3 of 69]. Both the adapalene 0.1% cream and 0.1% lotion formulations were well tolerated and acceptable to the study participants. The adapalene 0.1% lotion provides clinicians with a retinoid for the treatment of acne in a lotion formulation. PMID- 22779097 TI - Perturbation of cell cycle expression in keloid fibroblast. AB - The pathogenesis of keloid formation is poorly understood. The fibroblasts in keloid patients continue to multiply even after initial wound repair and are characterized by a persistent dermal fibroproliferative reaction and excessive extracellular matrix production. Most studies concentrate on the type of collagen produced within keloids and the cytokines that dominate the disease. There have been considerably fewer studies in the expression of messenger RNA level in key cell cycle genes of the keloid fibroblast. The aim of this study was to measure the messenger RNA expression of the key regulators of cell cycle, cell cycle cyclins, and cyclin-dependent kinases, and their inhibitors. PMID- 22779098 TI - Paget's disease of the breast. AB - The initial presentation of Paget's disease of the breast is an eczematous lesion, similar to contact dermatitis, in the skin of the breast at the areola and/or nipple and is refractory to usual topical treatments. It is frequent among women, especially those in their 50s and 60s. Most cases are associated with an in situ or underlying invasive breast neoplasia. The histopathology is usually diagnostic, with immunohistochemistry useful for its differentiation from melanoma and other types of tumors. Treatment should always be surgical with invasive procedures for the effective and complete removal of the breast tumor. PMID- 22779099 TI - Diagnosis and treatment of calciphylaxis. AB - Calciphylaxis occurs due to calcium deposition in arterioles, which leads to ischemic ulceration of overlying skin. Two-year mortality rates from sepsis ranges from 50% to 80%. Calciphylaxis is most common in hyperparathyroidism secondary to chronic renal impairment and rarely occurs in the setting of normal renal function. Biopsy of the calciphylaxis ulcer reveals calcium deposits lining the vascular intima. Tissue calcification may also be seen on plain radiographs. Calcium-phosphate metabolism should be normalized by treating any underlying hyperparathyroidism with bisphosphonates, parathyroidectomy, and/or cinacalcet in addition to dialysis in chronic renal failure. Intravenous sodium thiosulfate has been used successfully to treat renal and normo-renal calciphylaxis. Sodium thiosulfate displaces calcium ions from calcium deposits to form calcium thiosulfate, which is excreted by the kidneys or dialyzed. Systemic glucocorticoids may prevent ulceration of early plaques of calciphylaxis. Hyperbaric oxygen, skin grafting, and iloprost infusions are useful adjuncts in the management of this debilitating condition. PMID- 22779100 TI - "I always read my own slides". "I never read my own slides". PMID- 22779101 TI - Pellagra. AB - Pellagra was first described in the 18th century as an epidemic in the poverty stricken Spanish countryside by Gaspar Casal. Pellagra did not appear in the United States until the turn of the 20th century. It then ravaged the Southern United States and was not eliminated until the 1940s. This short report will redact the descriptions of pellagra in two early textbooks of dermatology. The first, published in 1897 before cases of pellagra were recognized in the United States, and, the second, published in 1915 in the midst of the epidemic. The text published in 1915 described in detail the medical signs and symptoms of pellagra particularly as they relate to the skin, as well as speculations as to its cause. The complicated story of the socioeconomic situation of the Southern United States and the hunt for the cause of pellagra will also be discussed briefly. PMID- 22779102 TI - Mycetoma. PMID- 22779103 TI - Exclusive plaque psoriasis of the lips: efficacy of combination therapy of topical tacrolimus, calcipotriol, and betamethasone dipropionate. AB - A 16-year-old unmarried woman presented with recurrent cracking of the lips indicated by the appearance of grayish white flakes since October 2004, which, in due course, shed off leaving behind an apparently normal mucous membrane. Chewing roasted corn treated with salt and lemon (bhutta) initially caused the lesions. Ever since, it has been a cause of its exacerbation. She never had any relief with either systemic or topical treatment. In fact, an obsession had overtaken her, resulting in a psychological setback. She denied regular drug use for any other ailment. Her menstrual cycle was normal. There was a positive history of psoriasis in her mother. Examination of the lips was conspicuous. It was marked by the presence of a well-circumscribed, moist, raised plaque (Figure 1). Its surface was irregular, with elevation and depression. It was made up of thick, grayish white scales, which were arranged in layers; however, Grattage/Auspitz sign could not be elicited. Fissuring was prominent but the buccal mucosa, surface of the tongue, gingiva, and palate were normal. The clinical examination did not reveal any evidence of skin and/or nail psoriasis/psoriatic arthropathy or any other systemic abnormality. Blood examination including total and differential leukocyte count, complete hemogram, and liver and renal function tests were normal. Biopsy of the representative lesion was subjected to serial sections. They were stained with hematoxylin-eosin to work up microscopic pathology. It revealed the presence of mounds of parakeratosis with numerous neutrophilic Munro microabscesses (Figure 2). Submucosal vessels were dilated and congested. Periodic-acid-Schiff (PAS) stain revealed fungal hyphae and spores within the parakeratotic layer. Colonies of Gram-positive cocci were also demonstrated on the surface of the mucosa. She was administered combination therapy, comprising topical tacrolimus (0.1%) ointment and calcipotirol hydrate (50 microg/g) plus betmethasone dipropionate (0.5 mg/g) twice a day for 7 days. A single bolus dose of fluconazole 450 mg orally was also administered. The response to treatment was favorable and the lesions showed regression (Figure 3). PMID- 22779104 TI - "Eruptive" facial syringomas: an inflammatory skin reaction? AB - A 26-year-old woman exhibited multiple, 1- to 3-mm eruptive asymptomatic papules, symmetrically distributed on the face. None of her family members had similar lesions. The papules first appeared in 2006 and gradually increased in number, particularly during her first pregnancy. She stated that the development of lesions was preceded by dermatitis. Physical examination revealed many flesh colored or slightly reddish, smooth-surfaced papules around the eyes, both cheeks, and temples (Figure 1 and Figure 2). The differential diagnosis included syringomas in an atypical location, cutaneous sarcoidosis, and periorificial dermatitis. Histopathologic examinations revealed aggregation of small tubular structures lined by two rows of epithelial cells, most of which were characterized by comma-like tails, giving them a tadpole shape. They were embedded in a fibrous connective tissue stroma in the dermis. These histopathologic findings were consistent with syringoma (Figure 3). PMID- 22779105 TI - Verrucous carcinoma of the tongue. AB - A 75-year-old woman with full dentures had a progressive growth on the tongue for the past 15 years. She reported ulceration of the lesion 4 months prior that was accompanied by pain and odinophagia. She denied addiction to alcohol or tobacco. On examination, there was an ulcerated, vegetating, verrucous lesion, with yellow whitish areas intermingled with erythematous areas, being infiltrated and having well-defined borders, on almost all areas of the back of the tongue (Figure 1). No adjacent lymphadenopathy was found. Biopsy of the tongue was compatible with verrucous carcinoma demonstrating squamous cell neoplasia with prevailing areas of rounded borders. There were "tunnels" filled with parakeratotic material surrounded by an extensive inflammatory response, plus isolated foci of neutrophils inside the tumor (Figure 2). There were relatively well differentiated neoplastic cells with little cytological atypia. In addition, there were several foci of individual or grouped dyskeratotic cells (Figure 3), plus tunnelling of parakeratotic material and an intratumor inflammatory response (Figure 4). Following surgical removal, the woman underwent chemotherapy and radiation treatment. PMID- 22779106 TI - Alcohol-based disinfectants. PMID- 22779107 TI - Ultrastructural characteristics of Nematopsis sp. oocysts (Apicomplexa: Porosporidae), a parasite of the clam Meretrix meretrix (Veneridae) from the Arabian Gulf, Saudi Arabia. AB - This paper describes the fine structure of oocysts of Nematopsis sp. (Apicomplexa, Porosporidae) found in the abductor muscles of seawater clams, Meretrix meretrix (Linnaeus, 1758) (Veneridae), collected near the city of Dammam (6 degrees 17'0"N, 50 degrees 12'0"E) in the Arabian Gulf off the coast of Saudi Arabia. Oocysts of an ellipsoidal shape were found among myofibrils of the abductor muscles of infected clams. Each oocyst is composed of an oocyst wall surrounding a single uninucleate vermiform sporozoite located in the lumen of the oocyst wall. The thin oocyst wall (0.70-0.85 microm thick) is composed of homogenous electron-lucent material formed by three layers of equal-thickness. The oocyst wall contains a plano-convex opercular-like structure about 2.5 microm in diameter and 0.75-0.90 microm thick, composed of a homogenous material with moderate electron density. The oocyst is of an ellipsoidal shape and is 15.6 +/- 0.6 microm long and 11.1 +/- 0.7 microm wide. Externally, the oocyst wall is surrounded by a complex dense network of numerous anastomosed microfibrils, which are attached to the oocyst wall, forming 2-3 layers and extending towards the periphery, at some points penetrating amongst the host cells. The myofibrils in some cases show evident aspects of lysis as a consequence of the appearance of lysosome-like vesicles. Lacking knowledge of a complete life cycle and/or molecular data precluded the conclusive identification of this species. PMID- 22779108 TI - Phylogenetic characterization of a microsporidium (Nosema sp.) isolated from the mulberry pest, Hemerophila atrilineata. AB - Microsporidia are a group of obligate intracellular unicellular eukaryotes that can parasitize a wide variety of other eukaryotes ranging from protists to invertebrates and vertebrates. In this study, we examined the microsporidium Nosema sp. isolated from the mulberry pest, Hemerophila atrilineata Butler, 1881, named herein "Nosema sp. HA". The fresh spores were long oval in shape, 3.8 +/- 0.4 microm in length and 1.9 +/- 0.3 microm in width. Analysis of tissue infection of silkworm, Bombyx mori Linnaeus, 1758, indicated that the midgut, Malpighian tubules, muscle, fat body, silk glands, hemocytes, nerve tissue and gonads of silkworm were infected with Nosema sp. HA. The complete rRNA gene sequence of this microsporidium contained 4 305 base pairs (GenBank Accession JN882299), including the large subunit rRNA (2492 bp), the internal transcribed spacer (187 bp), the small subunit rRNA (1232 bp), the intergenic spacer (279 bp) and the 5S region (115 bp). The organization of the rRNA gene is 5'-LSU-ITS-SSU IGS-5S-3'. Phylogenetic analysis, comparison of sequence identities and the arrangement in the rRNA gene subunits suggested that this isolate is separate from other Nosema species. PMID- 22779109 TI - Does Toxoplasma gondii infection affect cognitive function? A case control study. AB - According to studies, latent Toxoplasma gondii infection may affect several functions of the human brain. Here we search for the association between latent toxoplasmosis and cognitive performance. We tested 70 individuals for latent T. gondii infection. There were 26 Toxoplasma-infected subjects and 44 Toxoplasma free subjects. Within these two groups we assessed cognitive performance using a set of standardized, widely recognized neuropsychological tests: Trail Making Test, Stroop Test, Verbal Fluency Test, Digit Span Test and N-back test. The relationship between chronic toxoplasmosis and cognitive performance was assessed, with adjustment for age and sex. Patients with latent toxoplasmosis performed worse on one neuropsychological test, N-back Test--percentage of correct answers (beta -8.08; 95% CI - 15.64 to -0.53; p < 0.05) compared to seronegative patients. However, after adjustment for age and sex, no statistically significant associations between latent toxoplasmosis and the scores on any cognitive tests were noticed. As statistically significant relationship was not observed, this study does not confirm that chronic latent T. gondii infection affects cognition. PMID- 22779110 TI - Margaritaella gracilis gen. n. et sp. n. (Eucestoda: Proteocephalidea), a parasite of Callichthys callichthys (Pisces: Siluriformes) from the Parana River basin, Argentina. AB - Margaritaella gracilis gen. n. et sp. n. (Proteocephalidea: Proteocephalinae) found in the intestine of Callichthys callichthys (Linnaeus) from the Parana River basin is described. The new genus is placed in the Proteocephalinae because of the medullary position of the genital organs. It differs from all known genera included in the Proteocephalinae by the following combination of characters: 1) scolex with a conspicuous cluster of drop-shaped gland cells posterior to suckers; 2) strobila with a low number of proglottides, all much longer than wide; 3) testes arranged in one field, composed of two parallel rows of testes separated by the uterus; 4) ovary delicate, H-shaped, with branches slender and deeply folliculate at the edges, located at 25-35% from the posterior end; 5) uterus largely extended posterior to the ovary but not reaching the end of proglottis; and 6) vitelline follicles in two narrow lateral bands, largely extended posterior to the ovary. Scanning electron microscopy revealed three types of microtriches on the tegument surface: acicular and capiliform filitriches and gladiate spinitriches. The relative size of the ovary, a character recently used in the systematics of the proteocephalidean cestodes, was calculated for the new species and compared with other species of the group. M. gracilis is the first record of a proteocephalidean cestode parasitizing a callichthyid catfish. PMID- 22779111 TI - A new hyperapolytic species, Trilocularia eberti sp. n. (Cestoda: Tetraphyllidea), from Squalus cf. mitsukurii (Squaliformes: Squalidae) off South Africa with comments on its development and fecundity. AB - A new species of tetraphyllidean cestode in the genus Trilocularia is described from an undescribed shark species, Squalus cf. mitsukurii, off the coast of South Africa. Trilocularia eberti sp. n. is the second known member of its genus, and like its congener, T. gracilis (Olsson, 1866-1867) Olsson, 1869, is extremely hyperapolytic, dropping proglottids from its strobila while they are still very immature. Characteristic of the genus, it possesses a distinctive scolex with triloculated bothridia, but differs conspicuously from its congener in its possession of an anterior loculus that is much larger in width relative to the paired posterior loculi, and also in its possession of an anterior, enlarged region of its free proglottids that is triangular with a slit-like ventral aperture, rather than rounded and cup-like. This anterior region of the free proglottid is used in attachment, and its development is described. For assessment of fecundity, an attempt was made to record all free proglottids of all ages found in both host individuals, and yielded an average estimate of 362 free proglottids being produced per individual worm of T. eberti sp. n. Both Trilocularia species parasitize sharks of the genus Squalus, and given the host specificity typically exhibited by tetraphyllideans and preliminary examinations of other members of this shark genus, it is likely that other Squalus species will be found to host additional new Trilocularia species. PMID- 22779112 TI - Five new species of philometrid nematodes (Philometridae) from marine fishes off Java, Indonesia. AB - Based on light and scanning electron microscopical studies, the following five species of the Philometridae (Nematoda: Dracunculoidea) are described from female specimens collected from marine fishes off the southwestern coast of Java, Indonesia: Philometra lobotidis sp. n. from the abdominal cavity of the Atlantic tripletail Lobotes surinamensis (Bloch) (Lobotidae, Perciformes); Philometra javaensis sp. n. from the abdominal cavity of the immaculate puffer Arothron immaculatus (Bloch et Schneider) (Tetraodontidae, Tetraodontiformes); Philometra psettoditis sp. n. from the musculature of the Indian spiny turbot Psettodes erumei (Bloch et Schneider) (Psettodidae, Pleuronectiformes); Philometroides indonesiensis sp. n. from the musculature of the hound needlefish Tylosurus crocodilus crocodilus (Peron et Lesueur) (Belonidae, Beloniformes); and Philometroides trichiuri sp. n. from the dorsal fin of the largehead hairtail Trichiurus lepturus Linnaeus (type host) and the savalai hairtail Lepturacanthus savala (Cuvier) (both Trichiuridae, Perciformes). All these new species are distinguished from their congeners parasitizing marine fishes by morphological (mainly the shape and structure of the cephalic and caudal ends and of the oesophagus) and biometrical features. Besides previously known Philometra pellucida (Jagerskiold, 1893) and Philometra ocularis Moravec, Ogawa, Suzuki, Miyazaki et Donai, 2002, they are the only nominal philometrid species recorded from Indonesian waters. PMID- 22779113 TI - Can a specialist parasite species of a widespread and common host species be rare? The case of Spinitectus inermis (Nematoda: Cystidicolidae) in eels Anguilla anguilla. AB - The claim by many authors that Spinitectus inermis (Zeder, 1800), a narrowly specific parasite of European eels Anguilla anguilla (L.), is a rare species is considered at three levels: its geographical range, its frequency of occurrence compared to other eel parasites and its relative abundance in component communities. The parasite is widely distributed in freshwater throughout the European range of the eel but its occurrence is erratic and unpredictable, being known from only 8 countries. Surveys of eel parasites in the United Kingdom and in Continental Europe show that it is present in only 13% of British and 29% of continental localities. This satisfies one of the criteria for rarity. When present, its prevalence ranges from 1.8% to 43.3%, so it can be considered rare in some localities but in a few it may be common and on occasion it may be the dominant species in the gastro-intestinal community. Populations of S. inermis are almost always characterised by high levels of overdispersion, even at low prevalence. The species also displays an ability to colonise a locality following introduction there. Overall it meets many of the criteria of a rare species including a restricted distribution and a low frequency of occurrence and so it can be considered to exhibit diffusive rarity. PMID- 22779114 TI - Two species of Rhabdochona (Nematoda: Rhabdochonidae) from the cyprinid fish Luciobarbus kersin (Heckel) in northern Iraq, including R. (Globochona) kurdistanensis sp. n. AB - A new nematode species, Rhabdochona (Globochona) kurdistanensis sp. n. (Rhabdochonidae), is decribed based on specimens collected from the intestine of the barbel Luciobarbus kersin (Heckel) (Cyprinidae) in the Greater Zab (type locality) and the Lesser Zab Rivers, Tigris River basin, Kurdistan Region, northern Iraq. It is mainly characterized by a prostom with 8 anterior teeth, the presence of basal prostomal teeth, bifurcated deirids, length ratio of the muscular and glandular portions of oesophagus (1:14.4-17.8), conspicuously short left spicule (180-204 microm), arrangement of genital papillae, nonfilamented eggs, and by having cuticular ornamentations on the tail tip (2 lateral denticular outgrowths in female and numerous fine spines in male). Description of a gravid female of Rhabdochona (Rhabdochona) sp. with 14 anterior prostomal teeth and filamented eggs, recorded from L. kersin of the Greater Zab River, is also provided. R. kurdistanensis sp. n. is the fifth valid species of Rhabdochona Railliet, 1916 and the only representative of the subgenus Globochona Moravec, 1972 recorded from Iraq. PMID- 22779115 TI - Distribution of Hatschekia pagellibogneravei (Copepoda: Hatschekiidae) on the gills of Pagellus bogaraveo (Teleostei: Sparidae) from Madeira, Portugal. AB - A population of the gill parasite Hatschekia pagellibogneravei (Hesse, 1878) was studied on one of its sparid fish hosts, the blackspot seabream, Pagellus bogaraveo (Brunnich), off the coast of Madeira Island, Portugal, northeast Atlantic. Very high infection levels of this copepod were detected, with no significant seasonal differences. Abundance was negatively correlated with fish size. There were significant differences in the distribution of this copepod among the gill arches of the host, which seem to be best explained by differences in water flow within the gill habitat. PMID- 22779116 TI - Decoding population genetics: impact on tuberculosis control and treatment. PMID- 22779117 TI - Role of a pattern-based approach in interpretation of transbronchoscopic lung biopsy and its clinical implications. AB - BACKGROUND: Transbronchial lung biopsy (TBLB) is commonly performed for confirming the tissue diagnosis of diffuse parenchymal lung diseases (DPLDs). There is an urgent need to establish guidelines for interpretation of TBLB in order to improve its diagnostic utility. METHODS: We retrospectively studied 916 consecutive patients (494 males; mean age 49 years) who underwent TBLB over a 5 year period (July 2005 to July 2010) at Vallabhbhai Patel Chest Institute. RESULTS: In 615 (67.1%) procedures, material obtained during TBLB was adequate for histopathology interpretation. Pathological features evaluated in each case were: alveolar architecture, inflammatory infiltrate, interstitial fibrosis, atypical cells, pigment deposition, honey-comb change and fibroblast foci. The cases were categorised on the basis of histopathology into six patterns: (1) adequate biopsy without a specific diagnostic abnormality (n = 137, 22.3%); (2) acute pneumonitis (n = 29, 4.7%); (3) neoplasia (n = 109, 17.7%); (4) chronic interstitial inflammation with or without fibrosis (n = 138, 22.4%); (5) granulomatous inflammation, (n = 186, 30.2%); and (6) other specific causes (n = 16, 2.6%). Definitive diagnosis could be made after correlation of TBLB histopathology with clinical and radiological features in 55.3% cases. CONCLUSIONS: TBLB appears to be an important diagnostic tool for the diagnosis of DPLDs. The use of a pattern-based approach to TBLB adds to its diagnostic yield and can be helpful in cases where open lung biopsy is not available. PMID- 22779118 TI - Socio-economic status of smokers presenting to the outpatient service: does chronic obstructive pulmonary disease make a difference? AB - BACKGROUND: Sparse published data are available on the impact of social and personal factors leading to tobacco smoking. Identification of social and economic motives underlying smoking can facilitate the efforts towards control of tobacco smoking. METHODS: A questionnaire was administered to 966 smokers attending the Chest Diseases Out-patient clinic at the Haseki Training and Research Hospital, Istanbul to collect demographic data from the participants. In all of them spirometry was performed. RESULTS: The participants with chronic obstructive pulmonary diseases (COPD) were less benefiting from social security system and they were less educated. Patients with COPD were generally living in cities. In this group the number of divorced patients were more than the other group. CONCLUSIONS: There are many factors causing individuals to initiate smoking. By eliminating these factors, mortality and morbidity rates caused by smoking will decline dramatically. This study aims to draw attention on personal and social factors for smoking. PMID- 22779119 TI - Pattern of drug-resistance and treatment outcome in multidrug-resistant pulmonary tuberculosis. AB - AIMS AND OBJECTIVES: To study the pattern of drug-resistance and treatment outcomes among patients with confirmed multidrug-resistant pulmonary tuberculosis (MDR-PTB). METHODS: A prospective study was conducted at Rajiv Gandhi Institute of Chest Diseases, Bengaluru, Karnataka, India. Between January 2005 and December 2008, 224 confirmed MDR-PTB cases were studied for various drug-resistance patterns, and their treatment outcomes were analysed until November 2010. Sputum culture and drug sensitivity tests (DST) were carried out at National Tuberculosis Institute, Bengaluru; DST was done for all first-line drugs except pyrazinamide. RESULTS: Of the 224 MDR-PTB patients, 146 (65.2%) were resistant to all first-line drugs, 39 (17.4%) to isoniazid, rifampicin and streptomycin; 19 (8.5%) to isoniazid, rifampicin and ethambutol; and 20 (8.9%) to isoniazid and rifampicin. Among them, 145 (64.7%) patients were cured, 5 (2.2%) had treatment failure, 10 (4.4%) died, and 64 (28.5%) defaulted. Among 145 cured cases, 100 (69%) were resistant to all first-line drugs, 23 (16%) to isoniazid, rifampicin and streptomycin, 11(8%) to isoniazid, rifampicin and ethambutol, and 11(8%) to isoniazid and rifampicin. CONCLUSIONS: The most common pattern observed in this study was resistance to all four first-line drugs followed by resistance to isoniazid, rifampicin and streptomycin. Patients resistant to all first-line drugs had early sputum culture conversion and better cure rate as compared to other resistance patterns. PMID- 22779120 TI - Exhaled breath condensate analysis in chronic obstructive pulmonary disease. AB - The increasing focus on airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD) has led to development and evolution of tools to measure it. Direct assessment of airway inflammation requires invasive procedures, and hence, has obvious limitations. Non-invasive methods to sample airway secretions and fluids offer exciting prospects. Analysis of exhaled breath condensate (EBC) is rapidly emerging as a novel non-invasive approach for sampling airway epithelial lining fluid and offers a convenient tool to provide biomarkers of inflammation. It has definite advantages that make it an attractive and a feasible option. It is a source of mediators and molecules that are the causes or consequences of the inflammatory process. Measurement of such markers is increasingly being explored for studying airway inflammation qualitatively and quantitatively in research studies and for potential clinical applications. These biomarkers also have the potential to develop into powerful research tools in COPD for identifying various pathways of pathogenesis of COPD that may ultimately provide specific targets for therapeutic intervention. The EBC analysis is still an evolving noninvasive method for monitoring of inflammation and oxidative stress in the airways. The limited number of studies available on EBC analysis in COPD have provided useful information although definite clinical uses are yet to be defined. Evolving technologies of genomics, proteomics, and metabonomics may provide deeper and newer insights into the molecular mechanisms underlying the pathogenesis of COPD. PMID- 22779121 TI - Tracheal diverticulum. PMID- 22779122 TI - Bronchoscopic management of benign bronchial stenosis by electrocautery and balloon dilatation. AB - Benign bronchial stenosis is managed by surgical or bronchoscopic methods. Although surgical approach is definitive, it is technically demanding and is costlier than bronchoscopic treatment. Here, we report the case of a 27-year-old female patient with symptomatic benign bronchial stenosis of the left main bronchus. The stenosis was dilated successfully through a fibreoptic bronchoscope by electrocautery followed by balloon bronchoplasty and application of mitomycin C. On follow up, there was no evidence of re-stenosis. PMID- 22779123 TI - Tracheobronchial compression by right-sided aortic arch in a middle aged male. AB - Exertional dyspnoea is a common symptom among middle-aged population. Diagnostic evaluation of such patients is often challenging and confusing. We report a patient presenting with exertional dyspnoea and an obstructive ventilatory defect on spirometry that was refractory to bronchodilator therapy. Careful review of the chest radiograph and spirometry pointed towards variable intra-thoracic airways obstruction as a cause of dyspnoea. Contrast enhanced computed tomography (CECT) of the thorax and bronchoscopy established the diagnosis of a right-sided aortic arch resulting in tracheobronchial compression and tracheomalacia. PMID- 22779124 TI - Giant solitary fibrous tumour of the pleura. AB - Solitary fibrous tumour of the pleura is a rare primary pleural neoplasm. These tumours are usually asymptomatic and are incidentally detected. Majority of these neoplasms are benign and surgical excision provides excellent results. With the widespread use of imaging and better diagnostic criteria, this tumour is likely to be detected more frequently. We encountered a patient with a giant solitary fibrous tumour of the pleura. In this report, we describe the case of a patient with a giant solitary fibrous tumour of the pleura, review the literature and present the details of management of this patient. PMID- 22779125 TI - Pulmonary disease due to Mycobacterium massiliense. AB - We report a case of a patient suffering from multidrug-resistant pulmonary tuberculosis (MDR-PTB) who later developed an invasive infection of the respiratory tract with a rapidly growing non-tuberculous mycobacteria (NTM), recently identified as Mycobacterium massiliense, closely related to M. abscessus. To the best of our knowledge, this is the first case of M. massiliense infection being reported from India. PMID- 22779127 TI - Difference in the outcome of patients with different grades of initial sputum positivity under the Revised National Tuberculosis Control Programme. PMID- 22779126 TI - Regression equations for spirometry in children aged 6 to 17 years in Delhi region. AB - BACKGROUND: Most of the studies carried out in India to develop regression equations for spirometry in children are now several years-to-decades old and had used equipment and measurement protocols that have since changed. Prediction equations using the current standardisation protocols for spirometry are not available. The lung health of the population may have changed too. OBJECTIVE: To develop regression equations for spirometry for children aged 6 to 17 years of north Indian origin in Delhi region. METHODS: School children of north Indian origin, as determined by mother tongue and parentage, aged 6 to 17 years were screened by a health questionnaire and physical examination and those found "normal" underwent spirometry according to the standardised procedure recommended by the American Thoracic Society/European Respiratory Society (ATS/ERS) task force in 2005. Pearson's correlation analysis was carried out to identify the predictor variables for spirometric parameters. Prediction equations were developed using the multiple linear regression procedure. The independent variables were entered in sequence of height, age and weight. R2, adjusted R2 and R2 change, standard errors of the estimate (SEE), and estimates of regression coefficients were obtained and the goodness of fit was examined. RESULTS: Data was obtained in 365 boys and 305 girls. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) peak expiratory flow rate (PEFR), forced expiratory flow rate at 50% and 75% exhalation of vial capacity (F50 and F75) and mean forced expiratory flow rate over the middle 50% of the vital capacity (F25 75) showed moderate to strong correlations with age, height and weight in both boys and girls. In both genders, the equations explained very high variability of FVC, FEV1 and PEFR as shown by the R2 values. The explained variability for flow rates was lesser, with that for F75 being the least. CONCLUSIONS: Regression equations for spirometry variables for children of north Indian origin in Delhi region have been developed. These represent the first such effort from India after the publication of the ATS/ERS task force 2005 guidelines on standardisation of spirometry. PMID- 22779128 TI - [Living means communicating]. PMID- 22779129 TI - [The informed patient generation: virtual networking - nursing care in real terms]. PMID- 22779130 TI - [Prescribing websites and apps (interview by Urs Luthi)]. PMID- 22779131 TI - [Communication and language in the elderly: speaking is healing]. PMID- 22779132 TI - [Heart failure: counseling improves the quality of life]. PMID- 22779133 TI - [The architect transfers the keys]. PMID- 22779134 TI - [Patient education program: learning to live with cancer]. PMID- 22779135 TI - [Insecurity of parents is almost greater today (interview by Martina Camenzind)]. PMID- 22779136 TI - [Master plan for education in nursing careers: ambitions in the ant hill]. PMID- 22779137 TI - [No quarrel between the ancients and the moderns!]. PMID- 22779138 TI - [Collaboration between nurses and physicians: high level training is a sizeable asset]. PMID- 22779139 TI - [An innovative approach with delusional patients: crisis dialogue]. PMID- 22779140 TI - [CTR Day 2012: Missions in full evolution]. PMID- 22779141 TI - [Metamorphic or prenatal massage: liberation of prenatal schemas]. PMID- 22779142 TI - [The informed patient is prepared]. PMID- 22779143 TI - Mobile health technology and the law. PMID- 22779144 TI - Tar Heel footprints in health care: Cherene Allen-Caraco, QMHP, QDDP. PMID- 22779145 TI - North Carolina's mental health workforce: unmet need, maldistribution, and no quick fixes. AB - BACKGROUND: Recent data show a maldistribution of psychiatrists in North Carolina and critical shortages in some areas. However, only 11 entire counties have official mental health professional shortage designation. METHODS: This paper presents estimates of the adequacy of the county-level mental health professional workforce. These estimates build on previous work in 4 ways: They account for mental health need as well as provider supply, capture adequacy of the prescriber and nonprescriber workforce, consider mental health services provided by primary care providers, and account for travel across county lines by providers and consumers. Workforce adequacy is measured at the county level by the percentage of rieed for mental health visits that is met by the current supply of prescribers and nonprescribers. RESULTS: Ninety-five of North Carolina's 100 counties have unmet need for prescribers. In contrast, only 7 have unmet need for nonprescribers, and these counties have inadequate numbers of prescribers as well. To eliminate the deficit under current national patterns of care, the state would need about 980 more prescribers. LIMITATIONS: Data limitations constrain findings to focus on percentage of met need rather than supplying exact counts of additional professionals needed. Estimates do not distinguish between public and private sectors of care, nor do they embody a standard of care. CONCLUSIONS: North Carolina is working to develop its mental health prescriber workforce. The Affordable Care Act provides new opportunities to develop the mental health workforce, innovative practices involving an efficient mix of professionals, and financing mechanisms to support them. PMID- 22779146 TI - Depressive symptoms and academic performance of North Carolina college students. AB - BACKGROUND: Depression negatively affects cognitive functioning and, consequently, academic performance. Studies of this association have yielded conflicting results and have not fully considered other factors that may play a role in academic performance. This study examines the relation between depression and academic performance in students at a large urban university in North Carolina. METHODS: We analyzed data from student responses to the 2008 cross sectional National College Health Assessment to create categories of depressive symptomatology. E-mail invitations to participate in the assessment were sent to 8,000 students at the university in an effort to obtain at least 900 responses, the minimum number considered valid for a campus of its size. We analyzed the responses of the 1,280 undergraduates who completed the survey. Logistic regression analyses were performed to examine associations between depressive symptoms and academic performance in this group. RESULTS: Students in the second, third, and fourth quartiles of depressive symptomatology had increased, though statistically non-significant, odds of having a lower cumulative grade average, even after adjustment for age, sex, year in school, race/ethnicity, substance use, and level of credit-card debt. This difference was most pronounced among students in the second quartile of depressive symptomatology. LIMITATIONS: This cross-sectional study did not allow for evaluation of causality. In addition, the self-report nature of this questionnaire could have led to some inaccuracy in reporting. CONCLUSIONS: Students reporting even a small number of depressive symptoms may be at increased risk for academic problems. PMID- 22779147 TI - North Carolina's evolving mental health system. Introduction. PMID- 22779148 TI - Public behavioral health care reform in North Carolina: will we get it right this time around? AB - North Carolina seeks to provide affordable and high-quality care for people with mental health, developmental disabilities and substance abuse conditions by reforming its behavioral health care system. This article presents an overview of current efforts to achieve that goal and discusses the challenges that must be overcome if reform is to be effective. PMID- 22779149 TI - North Carolina's behavioral health delivery system: a historical perspective. AB - This commentary provides an overview of the mental health system in North Carolina. It suggests that the key to building a mental health system is settling on a strategy, implementing it, evaluating it, and funding it. More than a decade after reform was passed in North Carolina, this state still has not settled on a strategy. PMID- 22779150 TI - Managed care: right or wrong for North Carolina. AB - Since 2005, Piedmont Behavioral Healthcare (PBH) has operated North Carolina's only managed care Medicaid waiver program. Legislation was recently passed requiring that the waiver program be expanded statewide by January 2013. Experience with the PBH model suggests that this expansion can result in significant savings without compromising quality or access. PMID- 22779151 TI - Planned changes in child/family/youth services at one LME/MCO. PMID- 22779152 TI - The role of critical access behavioral health agencies in a reformed behavioral health system. AB - This commentary discusses the role that Critical Access Behavioral Health Agencies (CABHAs) currently play in meeting the behavioral health needs of people in North Carolina, the opportunities and challenges that CABHAs will confront under the state's section 1915(b)/(c) Medicaid waiver, and the future of CABHAs under the Affordable Care Act. PMID- 22779153 TI - Mobile crisis management teams as part of an effective crisis management system for rural communities. AB - Mobile crisis management teams provide crisis prevention and intervention services in community settings. The Appalachian Community Services crisis management program shows how such teams can be used to effectively serve rural communities. PMID- 22779154 TI - Crisis intervention teams and mobile crisis management. PMID- 22779155 TI - Primary care/behavioral health integration efforts in North Carolina. PMID- 22779156 TI - Integrative care: what the research shows. PMID- 22779157 TI - Prevention, treatment, and recovery supports for those with substance use problems: opportunities for enhanced access and quality of care. AB - Substance use disorder is one of our nation's most significant public health problems. If unaddressed, an individual's addiction will negatively impact the family, community and the health care system. Despite major strides in the field of addiction treatment, major barriers still exist preventing the problem to be addressed. We propose some recommendations to help improve access to care. PMID- 22779158 TI - Mental health recovery. AB - North Carolina has new opportunities for orienting its mental health care system toward client recovery as the system shifts to managed care with the possibility of offering more innovative services. Ways of accomplishing this reorientation are explored and instances of progress are noted. PMID- 22779159 TI - The "crisis" crisis: Emergency department use and community resources in North Carolina's behavioral health crisis system. AB - An unprecedented number of North Carolinians are coming to hospital emergency departments with behavioral health needs. There are significant delays after emergency treatment as the patient awaits placement in an inpatient facility often requirig the patient to be "boarded" in the hospital. Any viable solution to this "crisis" crisis will require significant community collaboration. PMID- 22779160 TI - North Carolina's institutional bias: enforcing the ADA's integration mandate. AB - Last year, the US Department of Justice determined that the state of North Carolina was violating the Americans with Disabilities Act by inappropriately institutionalizing people in adult care homes rather than providing them with housing and appropriate supports in the community. The state's long-standing institutional bias must now be corrected. PMID- 22779161 TI - Meeting the challenges of community-based care. AB - North Carolina is responding to multiple and interrelated challenges associated with the housing and support services for individuals with mental health needs, particularly those currently living in Adult Care Homes. Addressing the concerns raised by federal agencies provides an opportunity to reshape community mental health services. PMID- 22779162 TI - Preparing to come home: Recommendations for transition planning from North Carolina's Money Follows the Person Demonstration Project. PMID- 22779163 TI - A hospital driven telepsychiatry initiative to improve patient care and reduce costs. PMID- 22779164 TI - Durham system of care: creating a foundation for community change. PMID- 22779165 TI - A snapshot of North Carolina's public mental health, developmental disabilities, and substance abuse service system. PMID- 22779166 TI - The Affordable Care Act: improved options for North Carolinians with mental illnesses. AB - The Affordable Care Act, the health reform law enacted in 2010, offers new options to improve the quality of and access to mental health care for North Carolinians. This commentary will discuss provisions of the law that have the potential to enhance the lives of individuals with mental illnesses. PMID- 22779167 TI - [Researches on relationship between genetic differentiation and chemical variation of Cinnamomum migao]. AB - OBJECTIVE: To study the relationship between the genetic diversity and chemical variation of Cinnamomum migao. METHOD: ISSR marker technique was used to research the genetic structure of 9 population, GC-MS was used to analyze the main ingredients of the volatile oil in C. migao. RESULT: The analysis on the main ingredients of the volatile oil showed that there were significant or extremely significant differences in 9 populations. The minimum variation index of population was Yunnan Funing and the maximum variation index of population was Guangxi Yueye. ISSR marker analysis showed that the average of polymorphic loci percentage (P) was 42.41%, expected heterozygosity (H) was 0.181 0, Shannon's information index (I) was 0.293 8, the Nei's genetic diversity (H(s)) in the group was 0.188 9, genetic differentiation index (G(st)) was 2.269 1. The relationship between the genetic diversity and chemical variation showed that there was no significant correlation between the main ingredients of the volatile oil and 4 indexes of genetic structure of C. migao. CONCLUSION: The genetic diversity of C. migao was relatively high at the population levels, while it is low within the population levels, the relationship between chemical variation and genetic diversity was not obvious, that may indicate that other factors causes the chemical variation of C. migao. PMID- 22779168 TI - [Cloning and sequence analysis of squalene synthase gene and cDNA in Glycyrrhiza uralensis]. AB - OBJECTIVE: To clone and sequence the open reading frame and genomic sequence of squalene synthase (SQS) from Glycyrrhiza uralensis. METHOD: The primers were designed according to cDNA sequence of SQS from G. glabra reported by Hiroaki HAYASHI, SQS cDNA was cloned with total RNA extracted from roots of G. uralensis. Specific fragments were amplified by RT-PCR and then were cloned and sequenced. SQS DNA was cloned with total DNA extracted from roots of G. uralensis. Specific fragments were amplified by PCR and then were cloned and sequenced. RESULT: GuSQS1 (GenBank accession number: GQ266154) was 1 242 bp in length encoding proteins with 412 amino acid. NCBI Blast x search results showed GuSQS1 had the highest amino acid similarity to the corresponding proteins from G. uralensis. The identities of GuSQS1 with the two proteins were 98. 55% and 88. 62%. SQS (GenBank accession number: GQ180932) gene with 4 484 bp containing 13 exons and 12 introns was then amplified by PCR with genomic DNA extracted from roots of G. uralensis. CONCLUSION: These findings of cloning and sequencing the open reading frame and genomic sequence of squalene synthase (SQS) from G. uralensis brought some new clues for the further exploration of SmSQS function in sterol and terpenes biosynthesis. PMID- 22779169 TI - [Testing methods for seed quality of Cyathula officinalis]. AB - OBJECTIVE: To study testing methods of seed quality, and provide a basis for establishing seed testing specification of Cyathula officinalis. METHOD: Referring to the Specifications for Agricultural Seed Testing, the optimal testing methods of seed quality of C. officinalis were screened. RESULT AND CONCLUSION: The testing method for C. officinalis seed quality has been initially established. At least 8 g seeds should be sampled and passed through 20-mesh sieve for purity analysis. The phenotypic observation and size measurement were used for authenticity testing. The seeds were inoculated directly on PDA medium, cultured 5 days on 28 degrees C for seed health testing. The weight of 1 000 seeds was determined by using the 500-seed method. The water content of the seeds was determined under the higher temperature (133 +/- 2) degrees C for 3 hours. The seeds were dipped into 0.1% TTC solution 3 hours for determining viability. The seeds were cultured on pleated paper at 25 degrees C for 2-9 days for germination testing. PMID- 22779170 TI - [Preparation and in vitro release characteristics of pulsed-release tablets of Apocynum venetum]. AB - OBJECTIVE: Using Apocynum venetum as a model drug to prepare pulsed-release tablets based on diffusion, swelling, osmotic pressure mechanism and to evaluate the release characteristics. METHOD: The pulsatile release tablets were prepared by film coating methods using HPMC E5 and Eudragit The effect of formulation on pulsatile release of A. venetum was investigated. RESULT: The pulsed-release tablet was prepared by a swelling layer coating which contains HPMC E5 and a controlled-release membrane containning Eudragit. The delayed release time of the tablets was (5.0 +/- 0.5) h. CONCLUSION: The pulsatile release characteristics of A. venetum pulsatile release tablets were confirmed in vitro. PMID- 22779171 TI - [Preparation and in vitro release characteristics of vincristine sulphate loaded poly (butylcyanoacrylate) nanoparticles]. AB - OBJECTIVE: To prepare vincristine sulphate loaded poly (butylcyanoacrylate) nanoparticles (VCR-PBCA-NPs) and to investigate the in vitro release charactersitics. METHOD: VCR-PBCA-NPs were prepared by emulsion polymerization method, and characterized for morphology, particle size, drug encapsulation efficiency and loading efficiency. The formulation was optimized using central composite design and response surface methodology. In vitro release study of VCR PBCA-NPs was performed by dialysis technique. Model fitting was used to determine the kinetics and to discuss the mechanism. RESULT: The nanoparticles were spherical and uniform with a mean diameter of (98.9 +/- 3.05) nm. The drug encapsulation efficiency and loading efficiency were (55.23 +/- 0.96)% and (7.87 +/- 0.11)%, respectively. In vitro release results showed that 63.66% of VCR was released from VCR-PBCA-NPs in 4 h, and the Weibull model fitted VCR release pattern best. CONCLUSION: The VCR-PBCA-NPs prepared in this study showed sustained release compared with VCR solution. PMID- 22779172 TI - [Study on quality indicators for concentration process of supernatant obtained in first ethanol precipitation in production of Danshen injection]. AB - According to the effect of second ethanol precipitation (SEP) in the production of Danshen injection, the indicators for controlling the quality of a concentration process of the supernatant obtained in the first ethanol precipitation (FEP) were investigated. The concentrated supernatants of FEP with different constituents were prepared and treated with the same amount of ethanol. The parameters which affect phenolic compound retention ratios in SEP supernatant were found using a stepwise regression method. Phenolic compound contents in SEP supernatant were mainly affected by pH and caffeic acid content of the concentrated supernatant of FEP. Caffeic acid content and pH should be set as quality indicators and strictly controlled in concentrating the supernatant of FEP. PMID- 22779173 TI - [Dual-index sequence analysis of common and variant peak ratio in far-infrared fingerprint of Pyritum]. AB - OBJECTIVE: To set up the dual-indexes sequence analytical method for far-infrared fingerprint in which the dual indexes are common peak ratio and variant ration. METHOD: Two new indexes, common peak ratio and variant peak ratio, were applied and their values were calculated by means of sequential analysis, in which each Pyritum sample's far-infrared fingerprint spectra were set up and the common peak ratio sequences were arranged in order of size in comparision with other samples. RESULT: The analytical results suggested that samples S3 and S4, S5, S6 and S7, S8 and S9 from the same region showed higher common peak ratio and lower variant peak ratio. However, the sample S1 from Anhui showed little similarity with others. CONCLUSION: The method, applied to distinguish Pyritum of different areas and batches, is reasonable to characterize of traditional Chinese medicine. PMID- 22779174 TI - [Quantitative analysis of four alkaloids in Xianglian preparations by QAMS method]. AB - OBJECTIVE: To examine the feasibilities of the method, quantitative analysis of multi-components by single marker (QAMS) for determination of four alkaloids in Xianglian preparations. METHOD: A HPLC method was developed to determine the contents of four alkaloids, epiberberine, coptisine, palmatine and berberine in Xianglian preparations. Berberine was selected as the internal reference substance, and 3 relative correction factors to berberine were calculated. The contents of the four alkaloids in 16 batches of samples were determined by both external standard method and QAMS. The new method was evaluated by comparing the quantitative results with of the external standard method. RESULT: No significant differences were found between the quantitative results of four alkaloids in 16 batches of samples determined by the two methods. CONCLUSION: QAMS is feasible for determination of four alkaloids simultaneously, and the developed method can be used for quality control of Xiang Lian preparations. PMID- 22779175 TI - [Study on influence of glucoside Tripterygium total tablets on metabolism in rats by NMR metabonomic technique]. AB - OBJECTIVE: To investigate the toxic effects of Glucoside Tripterygium total on rats with nuclear magnetic resonance (NMR)-based metabonomic method. METHOD: The influence of intragastric administration of Glucoside Tripterygium total suspension at two different doses on endogenetic metabolites in normal rat urine was determined with bio-NMR method then analyzed by pattern recognition technique and partial least-squares discriminant analysis (PLS-DA). Histopathological analysis was carried out. RESULT: Escalations of concentrations of urinary taurine, TMAO and glucose as well as reductions of concentrations of urinary citrate and 2-oxoglutarate were found by analysis of the 1H-NMR spectra, which was coincident with the result of histopathological analysis. The result of pathological examination indicated that pathologic change was not observed in nephridial tissue, but there were obvious changes in hepatic tissue. CONCLUSION: The urinary metabomic spectra were closely associated with the hepatic toxicity, which manifested the mitochondrial dysfunctions, the abnormal energy metabolism in TCA cycle as well as the abnormal glucose metabolism. PMID- 22779176 TI - [Chemical constituents of Halenia elliptica]. AB - OBJECTIVE: To study the chemical constituents of Halenia elliptica. METHOD: The air-dried whole plants of Halenia elliptica were extracted with 90% EtOH. The EtOH extract was condensed to a small amount of volume and extracted with petroleum ether, EtOAc and n-BuOH, successively. The compounds were isolated and purified by column chromatography from the EtOAc fraction, and identified based on spectral analyses (MS, 1H-NMR, 13C-NMR). RESULT: 12 compounds were isolated from H. elliptica, and characterized as 8-hydroxy-2-methylchromone (1), 5-methoxy 2-methylchromone (2), 7-epi-vogeloside (3), coniferl aldehyde (4), sinapaldehyde (5), norbellidifolin (6), 1-hydroxyl-2,3,4,6-tetramethoxyxanthone (7), 1-hydroxyl 2,3,4,7-tetramethoxyxanthone (8), 1-hydroxyl-2,3,5-trimethoxyxanthone (9), together with azelaic acid, beta-sitosterol, and oleanolic acid. CONCLUSION: Compounds 1, 2 were new natural compounds and compounds 3-6, 10 were obtained from H. elliptica for the first time and compound 6 showed inhibitory activities against HBsAg and HBeAg secretion with IC50 value of 0.77 and < 0.62 mmol x L( 1), respectively. PMID- 22779177 TI - [Chemical constituents from herbs of Erigeron breviscapus]. AB - OBJECTIVE: To study the chemical constituents from herbs of Erigeron breviscapus. METHOD: The compounds were isolated and purified by various chromatographic techniques. Their structures were identified on the basis of physicochemical properties and spectral analysis. RESULT: Twelve compounds were isolated and structurally identified as quercetin-3-O-beta-D-glucoside (1), 5, 7 dihydroxychromone (2), 3-O-caffeoyl-gamma-quinide (3), naringenin (4), 3, 5-di-O caffeoylquinic acid (5), 3,4-di-O-caffeoylquinic acid (6), 4, 5-di-O caffeoylquinic acid (7), 1,3-di-O-caffeoylquinic acid (8), 1, 5-di-O caffeoylquinic acid (9), 3-O-caffeoylquinic acid (10), 4-O-caffeoylquinic acid (11) and chlorogenic acid (12). CONCLUSION: Compounds 1-4 were isolated from this plant for the first time. PMID- 22779178 TI - [Determination of twelve ginsenosides in Panax ginseng by HPLC]. AB - OBJECTIVE: To determine the contents of twelve ginsenosides in the root of Panax ginseng by HPLC. METHOD: The analysis is carried out at room temperature on a Luna NH2 column (4.6 mm x 150 mm, 5 microm) eluted with acetonitrile and water as the mobile phases in a gradient elution. The flow-rate was 1.0 mL x min(-1), the detection wavelength was 203 nm. RESULT: Twelve ginsenosides (Rh2, Rh1, Rg2, Rg3, Rg1, Rf, Re, Rd, Re, Rb2, Rb3, Rb1) were separated at baseline within 60 min with good linearity (r > or = 0.999 5). The recovery rates were 98.1%, 95.3%, 96.1%, 95.6%, 97.3%, 98.6%, 98.0%, 96.4%, 96.1%, 97.6%, 96.8%, 96.9% (RSD < or = 3.0%). CONCLUSION: The method was simple,fast and could control the quality of P. ginseng effectively. PMID- 22779179 TI - [Capillary electrophoresis with field-enhanced stacking for determination of water-soluble active principles in Salvia miltiorrhiza var. miltiorrhiza f. alba]. AB - A simple and sensitive capillary electrophoresis method with field-enhanced stacking concentration for the analysis of protocatechuic aldehyde, protocatechuic acid, danshensu, rosmarinic acid and salvianolic acid B in Salvia miltiorrhiza var. miltiorrhiza f. alba was developed. The separation was achieved with a fused-silica capillary (75 microm x 50.2 cm, effective length was 40 cm) and a running buffer 15 mmol x L(-1) borax (pH 10.0) containing 20% CH3 OH. The UV detection wavelength was 210 nm. The applied voltage was 28 kV, and the cartridge temperature was 25 degrees C. Water plug was introduced from the anode by 0.5 psi x 4 s before injection. Sample was injected by electrokinetic injection - 8 kV x 3 s. The linear range of protocatechuic aldehyde is 3.0-60.00 mg x L(-1) (R2 = 0.999 8); that of protocatechuic acid, danshensu, rosmarinic acid and salvianolic acid B are 1.0-20.00 mg x L(-1) (R2 are 0.999 1, 0.999 4, 0.998 9 and 0.999 8, respectively), and the limits of detection of five analyts are 0.55, 0.40, 0.25, 0.32, 0.38 microg x L(-1), respectively, Stacking factor is higher and precision is satisfactory. The recoveries ranges were from 97.3% to 99.8%. The proposed method was used to determine the protocatechuic aldehyde, protocatechuic acid, danshensu, rosmarinic acid and salvianolic acid B in S. miltiorrhiza var. miltiorrhiza f. alba. The proposed method is simple, rapid, accurate and high sensitivity, and can be used to control of the quality of S. miltiorrhiza var. miltiorrhiza f. alba. PMID- 22779180 TI - [Research on HPCE fingerprint of eupolyphaga steleophaga]. AB - OBJECTIVE: To set up the fingerprint of HPCE for medicinal material Eupolyphaga Steleophaga. METHOD: Separation was performed at 25 degrees C on an Agilent uncoated silica capillary column (40 cm x 75 microm) with 20 mmol x L(-1) borax buffer solution (pH 9.44) as CE buffer. The isolating voltage was 13 KV, and the DAD detection was set at 265 nm. RESULT: The characteristic peak of fingerprint of Eupolyphaga Steleophaga was consisted of 6 common peaks. CONCLUSION: The method can be used for the quality control of Eupolyphaga Steleophaga. PMID- 22779181 TI - [Simultaneous determination of 6 active components in Chrysanthemum morifolium by HPLC]. AB - OBJECTIVE: To develop a HPLC method quantitative method for simultaneous determination of chlorogenic acid, 1, 5-dicaffeoylquinic acid, isochlorogenic acid A, isochlorogenic acid C, luteolin-7-O-beta-D-glucoside and apigenin-7-O beta-D-glucoside in Chrysanthemum morifolium Ramat. METHOD: A Phenomenex Gemini NX C18 column (4.6 mm x 250 mm, 5 microm) was used with CH3 OH and 0.4% H3PO4 as mobile phases. The flow rate was 1 mL x min(-1), the column temperature was 25 degrees C, and the detection wavelength was set at 350 nm. RESULT: The 6 active components were in baseline separation. The linearity of this method was good (r > or = 0.999 7), and the average recoveries were 100.6% - 102.4%, RSD < 3%. Except isochlorogenic acid A, the contents of the determined components in the steam-blanched flower heads were significantly higher than those non blanched. The contents of chlorogenic acid and isochlorogenic acid A in the steam-blanched semiopened flower heads were higher than fully opened ones by 53% and 41%, respectively. CONCLUSION: The method is sensitive, accurate, reliable and repeatable, which can be used for quality evaluation of Chrysanthemum. PMID- 22779182 TI - [Study on HPLC fingerprint characteristics and chemotaxonomy of Pulsatilla medicinal plants]. AB - OBJECTIVE: To establish HPLC characteristic fingerprints of the saponins in Pulsatilla medicinal plants, and provide the basis for authentication and classification of Pulsatilla species. METHOD: The HPLC profiles were determined at 35 degrees C on a Symmetry C18 column (4.6 mm x 250 mm,5 microm) eluted with water (A) and acetonitrile (B) as mobile phases in a linear gradient elution with the flowrate of 0.5 mL x min(-1). The elution program was as follows: 0-8 min, 90% A to 77% A, 8-25 min, changed to 71% A, 25-40 min, to 60% A, 40-50 min, to 50% A, 50-75 min, to 10% A, 75-80 min, to 0% A. The detection wavelength was set at 210 nm. RESULT: The different species of Pulsatilla showed different HPLC fingerprints, but with 10 common peaks. A cluster analysis of 14 accessions indicated that they were divided into four groups: all accessions from P. koreana were classified into group I, P. ambigua in group II, P. dahurica and P. turczaninovii in group III, and P. chinensis in group IV, respectively. The significant differences between P. koreana and P. dahurica, and between P. turczaninovii and P. ambigua were observed. CONCLUSION: The results obtained were in agreement with the traditional taxonomic study. The method was rapid and precise, not only can be used to classify and authenticate Pulsatilla species, but also provides important references for HPLC fingerprints and quality control of Pulsatilla medicinal plants. PMID- 22779183 TI - [Simultaneous determination of 7 alkaloid in herba Sophorae Alopecuroidis by HPLC]. AB - OBJECTIVE: To establish a method for determination of 7 alkaloid in Herba Sophorae Alopecuroidis by HPLC. METHOD: X-Brige C18 (4.6 mm x 200 mm, 5 microm) column was used with acetonitriles-0.05 mol x L(-1) KH2PO4 solution (2.0 mL x L( 1) triethylamine) with gradient elution as the mobile phase and 1.0 mL x min(-1) as the flow rate. The detection wavelength was 205 nm. RESULT: Aloperin curve was linear in the range from 20.66 to 103.32 microg (r = 0.998 8) and the average recovery was 97.12% (RSD 7. 3%); sophoridine curve was linear in the range from 22.82 to 114.12 microg (r = 0.999 7) and the average recovery was 97.47% (RSD 3.0%); oxymatrine curve was linear in the range from 25.10 to 125.52 microg (r = 0.999 1) and the average recovery was 96.21% (RSD 4.5%); oxysophocarpine curve was linear in the range from 23.88 to 119.40 microg (r = 0.997 5) and the average recovery was 94. 64% (RSD 5.2%); matrine curve was linear in the range from 5.00 to 24.99 microg (r = 0.998 6) and the average recovery was 98.04% (RSD 5.4%); sophocarping curve was linear in the range from 4.69 to 23.46 microg (r = 0.999 6) and the average recovery was 96.24 (RSD 5.8%); lehmannine curve was linear in the range from 4.60 to 23.01 microg (r = 0.997 8) and the average recovery was 101.31% (RSD 4.3%). CONCLUSION: The method is accurate, simple and feasible. It can be used as a quality evaluation in Herba S. Alopecuroidis. PMID- 22779184 TI - [Diabetes mellitus ulcers treatment with Bletilla striata polysaccharide]. AB - The aim of this study was to evaluate the efficacy of Bletilla striata polysaccharide on diabetes mellitus ulcers. Diabetes mellitus animal model was established by single ip injection of streptozotocin (STZ, 50 mg x kg(-1)) with the criteria of blood glucose > or = 16.7 mmol x L(-1) after 72 h. 4 weeks after STZ injection, each animal received two full thickness incisional wounds (1.8 cm in diameter). The wounds then were divided into B. striata polysaccharide group and PBS group. Wound closure rate, fibroblast (FB) infiltration, hydroxyproline (OHP) content and myeloperoxidase (MPO) levels were examined on day 3, 7, 14, 21 post wound. The treatment of B. striata polysaccharide significantly facilitated diabetes mellitus ulcers healing compared to PBS group. Histological analysis showed that B. striata polysaccharide markedly increased inflammatory cell infiltration in wound area. The herb also strongly evaluation of FB, OHP demonstrated a significantly increased in B. striata polysaccharide group. B. striata polysaccharide group promoted wound closure by means of enhanced inflammatory cell infiltration and re-epithelialization, and the promotion of FB and OHP levels. PMID- 22779185 TI - [Experimental studies on blood lipid regulating effects of shuanghua granules]. AB - Hyperlipidemia plays a vital role in cardiovascular disease, and threatens our lives. The aim of this paper is to study the effects of Shuanghua granules on blood lipid in normal mice and different hyperlipidemia models. Acute and endogenous hyperlipidemia was induced in mice with yolk and Triton WR-1339 respectively. The model of hyperlipidemia in rats was set up by feeding high cholesterol diet. Then preventive effects of Shuanghua granules was observed compared with lovastatin and Zhibituo. We found that Shuanghua granules 5.6, 11.3, 22.5 g x kg (-1) could significantly reduce the serum TG level in normal mice (P < 0.01, P < 0.05). No significant difference was found in liver index, serum TG and HDL-C levels. When the mice were treated with either yolk or Triton WR-1339 in the presence of Shuanghua granules, the plasma lipoprotein levels (TC and LDL-C) were significantly reduced (P < 0.01, P < 0.05). Shuanghua granules could reduce the serum TC, TG, LDL-C, MDA, NEFA and liver TC, TG, LDL-C levels, simultaneously raise serum and liver HDL-C, serum SOD, LPL, HL, LA levels of hyperlipidemia rats (P < 0.01, P < 0.05). Shuanghua granules also significantly reduced whole blood viscosity, RV, etaP, IER and IEA (P < 0.01, P < 0.05), and lowered fatty degeneration of liver tissue. Compared with hyperlipidemia model, there was no significant increase in faeces lipoids concentrations. The results confirmed the mechanism of blood lipid regulating effects of Shuanghua granules is probably related with its antioxidation, regulating hemorheology and improving LPA, HL, LA enzymatic activity. PMID- 22779186 TI - [Modulatory effect of triptolide on differentiation of human Th17 cells]. AB - OBJECTIVE: To investigate the effect of triptolide on the differentiation of human Th17 cells. METHOD: Human peripheral blood mononuclear cells, purified CD4+ T cells and CD4+CD45RA- memory T cells were treated with various concentrations of triptolide in vitro. Cell proliferation was determined by MTT assay. Flow cytometry was used to analyze the intracellular expression of IL-17 and IFN gamma. Cytokine production of IL-17 and IFN-gamma was measured by ELISA. RESULT: Cell proliferation, intracellular expression of IL-17 and IL-17 secretion were inhibited by triptolide in a dose-dependent manner. IFN-gamma expression and production were also inhibited by triptolide. CONCLUSION: Triptolide inhibits the differentiation of human Th17 cell. The observation may indicate at least one of the mechanisms of the immunosuppressive and anti-inflammatory effects of triptolide. PMID- 22779187 TI - [Icariin reduces mitochondrial oxidative stress injury in diabetic rat hearts]. AB - OBJECTIVE: To investigate the effects of icariin on cardiac functions and mitochondrial oxidative stress in streptozotocin (STZ)-induced diabetic rats. METHOD: Male SD rats were randomly divided into normal control group, icariin control group, diabetic group, and diabetic groups administered with a low dose (30 mL x kg(-1) x d(-1), ig) or a high dose (120 mL x kg(-1) d(-1), ig) of icariin for 8 weeks. The body weight, blood glucose, cardiac functions, left ventricular weight, and myocardial collagen level were assayed. The cardiac mitochondrial reactive oxygen species (ROS) level, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were measured. RESULT: Treatment with icariin reduced the losing of body weight in diabetic rats. Icariin markedly reduced the ratio of ventricular weight and body weight, increased the left ventricular develop pressure and +/- dp/dt(max), and decreased the left ventricular end diastolic pressure in diabetic rats. The myocardial collagen and the level of cardiac mitochondrial ROS in diabetic rats were all markedly reduced by icariin. Furthermore, high dose of icariin significantly decreased the mitochondrial MDA level and increased SOD activity in diabetic rat hearts. CONCLUSION: Treatment with icariin for 8 weeks markedly improved the cardiac function, which may be related to reducing mitochondrial oxidative stress injuries in diabetic rats. PMID- 22779188 TI - [Treatment of premenstrual syndrome with Chinese medicine formula, baixiangdan capsule: implications for neuron viability and GABA(A) receptor modulation in rat cortex]. AB - OBJECTIVE: To explore the effects of Baixiangdan capsule (BXD), a Chinese medicinal formula, on the premenstrual syndrome (PMS) rats with Liver-qi invasion and the possible underlying micro-mechanisms. METHOD: Wistar rats were randomly assigned to two groups, nomal group and BXD group After evaluated by macro behavior observation and open-field test, MTT assay and the whole-cell patch clamp recording were performed respectively to evaluate the effects of serum from BXD capsule-treated rats on the viability and GABA(A) R-induced currents of cortical neurons in vitro. RESULT: In the open-field test, the crossing score, rearing score and total score of BXD rats decreased significantly (P < 0.05), compared by the normal rats. Compared with cells exposed to serum of normal rats, the viability values of those incubated with serum of BXD group for 24 h and 48 h significantly increased (P < 0.05), measured by MTT assay. The results of whole cell patch clamp recording showed that concentration-response relationship curves revealed an EC50 value of (29.0 +/- 4.4) micromol x L(-1) and a Hill coefficient of 1.07 for normal-exposed cultures, (63.5 +/- 8.2) micromol x L(-1), 1.04 for BXD-exposed cultures after incubation for 24 h. Furthermore, the difference in EC50 values was statistically significant (P < 0.01), that in the Hill coefficient was not obvious. CONCLUSION: BXD capsule could significantly decrease crossing score and total score of open-field test and effectively enhance the neuron viability and GABA(A) receptor activity in rat cortex. Paeonimetabolins I and paeonol may play a significant role in treating PMS model rats with Liver-qi invasion by BXD capsule, and paeonol may target at GABA(A) receptor, especially. PMID- 22779189 TI - [Effects of three traditional Chinese medicine with pungent-flavor, warm-nature and meridian tropism in lung on lung-yang deficiency rats induced by compound factors]. AB - OBJECTIVE: To observe the effects of three traditional Chinese medicine (TCM) such as Amomi Fructus Rotundus, Perillae Folium and Angelicae Dahuricae Radix on lung-yang deficiency rats induced by compound factors. METHOD: Lung-yang deficiency rats were established with three-factor combination, such as smoking (exogenous evil effect on lung), swimming in common and ice water (cold body and exhaustoin) and drinking ice water (inhale cold). Meanwhile, rats were given water extracts of the three TCM by intragastric administration for 24 days everyday. Indexes such as general behavior, weight, rectal temperature, back temperature and grip strength were observed. Blood was collected to determine NO, IgG in blood serum. Lung and heart were dissected to measure organs index. RESULT: The water extracts of Amomi Fructrs Rotundus, Perillae Folium and Angelicae Dahuricae Radix could markedly heighten weight, back temperature, grip strength, content of IgG in blood serum, reduce content of NO in blood serum, lung index and heart index. The water extracts of Amomi Fructrs Rotundus and Perillae Folium could heighten rectal temperature. CONCLUSION: Amomi Fructrs Rotundus, Perillae Folium and Angelicae Dahuricae Radix were TCM with pungent flavor, warm-nature and meridian tropism in lung, which could improve the symptoms of physique emaciation, aversion to cold of the back, weary and acratia and so on. It provides an important reference for the regularity of the properties theories about pungent-flavor, warm-nature and meridian tropism in lung. PMID- 22779190 TI - [Tissue distribution in mice of danshensu from sodium danshensu and Salvia miltiorrhiza injection]. AB - OBJECTIVE: To determine the concentration in mice of danshensu from sodium danshensu and Salvia miltiorrhiza injection and undertake comparative study of them as well as to assess the effect of other components of S. miltiorrhiza injection on the tissue distribution of danshensu. METHOD: Mice received intraperitoneal administration of sodium danshensu or S. miltiorrhiza injection (equal to danshensu 60 mg x kg(-1)) respectively, and was executed 30 minutes after administration. The concentration of danshensu in different tissues was separately determined by high performance liquid chromatographic method. RESULT: The characteristic profiles of sodium danshensu in different tissues were C(kidney) > C(spleen) > C(lung) > C(heart) > C(liver). The characteristic profiles of danshensu from S. miltiorrhiza injection in different tissues were C(kidney) > C(lung) > C(spleen) > C(heart) approximately C(liver). The concentration of danshensu in S. miltiorrhiza injection in liver and kindey was higher than sodium danshensu itself. CONCLUSION: It was suggested that the other components in S. miltiorrhiza injection influent the distribution profile in tissues of danshensu. PMID- 22779191 TI - [Effects of naokang erhao decoction on cognitive ability and hippocampal apoptosis-related proteins in diabetic rats]. AB - OBJECTIVE: To investigate the effects of Naokang Erhao decoction on the cognitive ability and the expression of Caspase-3, Bax and Bcl-2 proteins in hippocampus of type 2 diabetic rats. METHOD: The diabetes mellitus (DM) rat model was produced by intraperitoneal injection of streptozotocin and fed with high fat and sucrose diet. The Naokang Erhao-treated rats were intragastrically given different doses of Naokang Erhao, whereas the control and DM model groups were given double distilled water for 4 consecutive weeks. Learning and memory abilities of rats were tested with the Morris water maze. The expression of Caspase-3, Bax and Bcl 2 proteins in hippocampal CA1 region was measured by immunohistochemistry. RESULT: Both escape latency and swimming distance of type 2 DM rats were significantly prolonged in comparison of those in normal control (P < 0.01), and swimming time in the platform of previous quadrant was significantly shorter in model group (P < 0.01). Furthermore, the expression of Bcl-2 protein was decreased, while Caspase-3 and Bax in the hippocampus were increased compared with the control group (P < 0.01). Four weeks of treatment with Naokang Erhao decoction remarkably improved the learning and memory abilities of DM rats, increased the expression of Bcl-2 and decreased the expression of Caspase-3 and Bax in hippocampal CA1 region of model rats (P < 0.01 or P < 0.05). CONCLUSION: Naokang Erhao decoction may inhibit apoptosis by increasing the expression of Bcl 2 and reducing the expression of Caspase-3 and Bax in the hippocampus, and this may be one of the mechanisms by which Naokang Erhao decoction improves cognitive ability in DM rats. PMID- 22779192 TI - [Human pregnane X receptor-mediated transcriptional regulation of CYP3A4 by extracts of 7 traditional Chinese medicines]. AB - OBJECTIVE: To test whether 7 herbs stimulate human pregnane X receptor (PXR) mediated CYP3A4 transcription. METHOD: Transient cotransfection reporter gene assays were performed with human PXR expression plasmids and a reporter plasmid containing the XRES in the CYP3A4 gene promoter in HepG2 cells. RESULT: The aqueous extracts of Chrysanthemi Flos, Lycii Fructus, and Salviae Miltiorrhizae Radix et Rhizoma, and the methanol extracts of Chrysanthemi Flos, Crataegi Fructus, Lycii Fructus, Lonicerae Japonicae Flos, Dioscoreae Rhizoma,and Salviae Miltiorrhizae Radix et Rhizoma, activated human PXR-mediated transcription. CONCLUSION: The aqueous extracts of Chrysanthemi Flos, Lycii Fructus, and Salviae Miltiorrhizae Radix et Rhizoma, and the methanol extracts of Chrysanthemi Flos, Crataegi Fructus, Lycii Fructus, Lonicerae Japonicae Flos, Dioscoreae Rhizoma, and Salviae Miltiorrhizae Radix et Rhizoma are inducers of CYP3A4 by activating PXR, and thus may influence the metabolism of other substrates on CYP3A4. PMID- 22779193 TI - [Clinical study on naoxintong capsule for stroke recovery of Qi-deficiency and blood-stasis syndrome]. AB - OBJECTIVE: To study the efficacy and safety of Naoxintong capsule treatment of stroke recovery with Qi-deficiency and blood-stasis syndrome (cerebral infarction), and to compared the non-inferiority analysis with the positive drug Tongxinluo capsule. METHOD: Taking Tongxinluo capsules as control, randomized, double-blind, controlled, multi-center clinical experiments were studied. The evaluating indexes included the decrease of integral value of stroke patients, changes in traditional Chinese medicine, the improvement of the patient viability status (disability level), Chinese stroke scale (CSS), activities of daily living (DAL) scale and barthel index (BI ) points. RESULT: The total effect of the two groups, Chinese and other symptoms, showed no significant statistical significance. CONCLUSION: Naoxintong capsule stroke recovery, with Qi-deficiency and blood-stasis syndrome (cerebral infarction) has a therapeutic effect, and more secure. PMID- 22779194 TI - [Herbalism and germplasm of deltaleaf goldthread rhizome]. AB - Through textual research of herbalism about Chinese Goldthread Rhizome in different periods of ancients and some modern study, and analysis on correlativity between its name and different germplasm, it showed that the knowledge level of quality of the medicinal materials was gradually increased in its historical record of application by the society improvement and increasing of requirements and population from producing area, diversity of character to germplasm resources. The materials name of Chinese Goldthread Rhizome was from unitary to diversity and referred to the rhizomes of all plants of Coptis in China, while Deltaleaf Goldthread Rhizome took an important role in the evolution of Chinese Goldthread Rhizome. The aim of the work was to provide a reference for the correlative study of phylogeny, individual distribution, ecological environment and medical resources. PMID- 22779195 TI - [Preliminary study on classification and nomenclative system of Mongolian traditional medicine]. AB - Based on traditional medicine and traditional medicine knowledge and knowledge systems and their internal relations which consist of the main theoretical basis of traditional Mongolian medicine, classification and nomenclature system of the traditional Mongolian medicine were proposed. PMID- 22779196 TI - [Scientific supervision of compound preparation of traditional Chinese medicine and chemical drug]. AB - The application of the compound preparation of traditional Chinese medicine (TCM) and chemical drug in clinical has a long history. Drug regulatory requirements of the compound preparation of TCM and chemical drug in various periods were compared and analyzed, and the history and status of the way of scientific supervision of this preparation were summarized. This paper discussed the problems and deficiencies of the compound preparation of TCM and chemical drug, and put forward countermeasures and suggestions about to strengthen the scientific supervision of the compound preparation of TCM and chemical drug. PMID- 22779197 TI - Cancer in the oral area. PMID- 22779198 TI - New technologies. PMID- 22779199 TI - Oral and maxillofacial pathology case of the month. Angiomyoma (vascular leiomyoma). PMID- 22779201 TI - Oral cancer: diagnosis, treatment, and management of sequela. PMID- 22779200 TI - CAT of the month. Periodontal therapy may not affect adverse pregnancy outcomes (UT CAT #560). PMID- 22779202 TI - Management of the oral sequelae of cancer therapy. AB - Oral cancer and the oral sequelae of treatment for oral and other malignancies can significantly affect a patient's oral and systemic health, as well as have a profound impact on quality of life. Compromised oral health prior to, during, and following cancer therapy can affect treatment outcomes. Increasingly, dental professionals in the community are being called upon to provide care for these individuals. Radiation therapy is routinely used for tumors of the head and neck, delivering a concentrated radiation dose to the tumor, but also to the immediately surrounding tissue. Oral complications are related to the site radiated and the total radiation dose. Cancer chemotherapy is provided as a primary treatment for some cancers and as an adjunctive modality for other cancers. The goal is to eradicate the rapidly growing cells of the tumor, but chemotherapy is often toxic to other cells that rapidly divide normally including the oral mucosa. The use of combined chemotherapy and radiation is now considered standard for most locally advanced tumors of the head and neck. The toxicities of this combined therapy are essentially the same as with radiation alone, but develop more rapidly and are typically more severe when they reach maximum level. The most common oral sequelae of cancer treatment are: xerostomia, the sensation of a dry mouth as a result of damage to the salivary glands and/or medication; mucositis, the inflammation and ulceration of the oral mucosa; and infection as a result of the loss of mucosal integrity. Management of oral health during cancer therapy includes identifying at-risk patients, patient education, appropriate pretreatment interventions, and timely management of complications. Appropriate preventive and therapeutic measures will help minimize the risk of oral and associated systemic complications, improve treatment outcomes, and improve the patient's quality of life. PMID- 22779203 TI - Adjunctive diagnostic aids in oral cancer screening: an update. AB - During the past decade, several adjunctive aids have been introduced to the marketplace with the promoted goal of improving the dental practitioner's ability to screen for and identify oral premalignant and malignant lesions (OPMLs). These products include the OralCDx Brush Test, ViziLite Plus with TBlue, Microlux, VELscope Vx, Sapphire Plus, Identafi, and the DOE Oral Exam System. They are all marketed as aids for the clinician to use in addition to, not in lieu of, the accomplishment of a conventional oral examination (COE). Studies addressing the efficacy of these products when used in the general practice setting to screen for OPMLs are limited and conflicting. The ability to discriminate between truly dangerous OPML against the milieu of benign mucosal lesions remains a concern and further research is necessary to determine the true value of these products as marketed to the general practitioner. The attainment of a complete history and the accomplishment of a thorough and disciplined COE remains the foundation upon which the practitioner assesses the patient for OPMLs. Findings deemed suspicious or equivocal should be referred to an expert for further assessment or undergo immediate biopsy, while findings deemed innocuous should be re-evaluated within 2 weeks and referred to an expert for further assessment or undergo biopsy if still present. PMID- 22779204 TI - Oral health resources for cancer patients in Texas. AB - Over 1.4 million new cases of cancer are diagnosed each year, and many of these patients will, by necessity, be treated in private practice, including dental practice. Dental professionals play a key role in helping patients understand that good oral care can prevent or reduce oral complications. Treatment of oral cancers and other malignancies cause oral sequelae that can compromise patients' quality of life and dictate reduction or discontinuation of optimal therapeutic regimens, which in turn reduces the odds of long-term survival. This can be prevented or better managed if dental and medical health care providers work together. The purpose of this article is to identify the cancer centers associated with dental clinics and the dental practitioners in the state of Texas, including maxillofacial prosthodontists, with training and/or a special interest in providing oral care to cancer patients. To be included on the list, which will be available on the Dental Oncology Education Program (DOEP) Web site (doep.org), please contact Grady Basler at the DOEP office (grady@doep.org), or the Department of Public Health Sciences (214-828-8350). PMID- 22779206 TI - Value for your profession: Target prospective patients through local search marketing. PMID- 22779205 TI - Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas. AB - BACKGROUND: This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions. TYPES OF STUDIES REVIEWED: The panel members conducted a systematic search of MEDLINE, identifying 332 systematic reviews and 1,499 recent clinical studies. They selected 5 systematic reviews and 4 clinical studies to use as a basis for developing recommendations. RESULTS: The panel concluded that screening by means of visual and tactile examination to detect potentially malignant and malignant lesions may result in detection of oral cancers at early stages of development, but that there is insufficient evidence to determine if screening alters disease-specific mortality in asymptomatic people seeking dental care. CLINICAL IMPLICATIONS: The panel suggested that clinicians remain alert for signs of potentially malignant lesions or early-stage cancers while performing routine visual and tactile examinations in all patients, but particularly in those who use tobacco or who consume alcohol heavily. Additional research regarding oral cancer screening and the use of adjuncts is needed. PMID- 22779207 TI - Pathology of ocular lesions associated with gas supersaturation in white seabass. AB - Cultured juvenile white seabass Atractoscion nobilis (WSB) can suffer from intraocular emphysemas and exophthalmia in the hatchery environment. To identify the cause, two size-groups of WSB were exposed to five gas saturation levels, ranging from 98% to 122% total gas pressure (TGP), over a 96-h exposure period in 18 degrees C and 23 degrees C seawater. Histological examination revealed that the gross and subgross lesions associated with gas supersaturation included corneal and orbital emphysema, along with subretinal, optic nerve, and iridial hemorrhage. Corneal emphysema was the most prominent gross lesion, with the severity and prevalence increasing between size-groups and water temperatures as TGP increased. Following the same pattern was orbital emphysema, which affected more than 93% of the fish examined and caused hemorrhage in the subretinal space, around the optic nerve, in the iris, or a combination thereof. Iridial hemorrhage occurred in 91% of the fish examined and decreased significantly with fish size. The prevalence and severity of hemorrhage in the subretinal space increased significantly with TGP and fish size but not with temperature. Optic nerve hemorrhage was absent in small fish exposed at 18 degrees C but increased significantly with temperature and fish size. The reverse was true for the large fish. PMID- 22779208 TI - Effect of dietary vitamin E on cortisol and glucose responses to handling stress in juvenile beluga Huso huso. AB - An 8-week feeding experiment was conducted to investigate the effect of dietary vitamin E on the physiological response to handling stress in juvenile beluga Huso huso. Fish were fed six experimental diets supplemented with 0, 25, 50,100, 200, or 400 mg Dl-all-rac-alpha-tocopherol acetate/kg diet. At the end of the experiment, the fish in each tank were subjected to acute handling and air exposure stress. Cortisol and glucose were measured as the primary hormonal and secondary metabolic responses to the stressors, both before and 3 h after application of the stressors. The growth parameters and feed utilization rates were significantly lower in fish fed the diet not supplemented with vitamin E than in fish fed diets supplemented with vitamin E. Cortisol concentration was not affected by dietary treatment but glucose concentration was. Fish fed vitamin E at 0, 25, 100, and 400 mg/kg diet had higher concentrations of glucose than those fed vitamin E at 50 and 200 mg/kg. However, fish fed diets with 50 and 200 mg/kg exhibited higher growth rates. These results indicate that dietary vitamin E has some effect on plasma glucose but no effect on plasma cortisol. In general, when the stressors were applied to belugas, the glucose and cortisol responses were relatively low. This may be due to higher resistance and lower physiological responses to these types of stressors by this species or by chondrosteans in general. PMID- 22779209 TI - The effect of temperature and salinity on the elimination of enrofloxacin in the Manila clam Ruditapes philippinarum. AB - The effect of temperature and salinity on the elimination of enrofloxacin (EF) in Manila clams Ruditapes philippinarum was investigated. The clams, cultured under different temperatures and salinities (16 degrees C and 30 per thousand, 22 degrees C and 30 per thousand, or 22 degrees C and 20 per thousand), were exposed to EF at 5 microg/mL of water in a medicated bath. After a 24-h exposure, the concentration of EF in various tissues was measured by high-performance liquid chromatography and the elimination rate of EF in those tissues was investigated by regression analysis. After the treatment, the initial concentrations of EF among tissues were (in decreasing order) plasma > gill > visceral mass > foot > adductor muscle. In all tissues the elimination half-life (t1/2) of EF in the clams cultured at 22 degrees C and 20 per thousand and 16 degrees C and 30 per thousand were markedly longer than in those cultured at 22 degrees C and 30 per thousand, and the t1/2 at 16 degrees C and 30 per thousand was slightly longer than that at 22 degrees C and 20 per thousand. Slight differences were also observed in t1/2 values among various tissues. These data indicate that both temperature and salinity had significant effects on the elimination of EF in the Manila clams and that lower temperature or salinity could result in slower elimination. PMID- 22779210 TI - Farm level and geographic predictors of antibiotic use in Sri Lankan shrimp farms. AB - Black tiger shrimp Penaeus monodon farming is important for Sri Lanka's rural development plans. Consumer confidence is critical for the development and maintenance of export and domestic shrimp markets. Public concern about the use of antimicrobial drugs and chemicals on shrimp farms, however, could threaten market access. We sought to identify high-risk areas and farm-level risk factors for antimicrobial use to inform the core messages and strategic placement of extension programs to help farmers develop best management practices for antimicrobial use. We undertook a survey of 603 operating farms within the Puttalam district over 42 weeks. Lower stocking density and early harvest were associated with a lower risk of antimicrobial use, whereas standard management practices, including water treatment, feed supplements, probiotic use, pond fertilizing, disinfectant use, and pesticide use, were associated with increased risk. Spatial cluster detection found three significant clusters of antimicrobial using farms. Antimicrobials were more likely to be used in areas with lower farm density. Some of our counterintuitive findings are discussed from a socioecological perspective. A comprehensive understanding of why antimicrobials are used on shrimp farms requires an evaluation of the physical, epidemiological, and socioeconomic factors. PMID- 22779211 TI - Use of vaccination against enteric septicemia of catfish and columnaris disease by the U.S. catfish industry. AB - Vaccination is an effective strategy used for the protection of food animals against infectious diseases. A 2010 U.S. Department of Agriculture questionnaire examined U.S. catfish industry use (in 2009) of two commercial vaccines that provide protection against enteric septicemia of catfish (ESC) and columnaris disease, catfish producers' opinions regarding the percentage of vaccinated fish they expect to be protected, and producers' general expectations regarding survival of vaccinated fish compared with unvaccinated fish. During 2009, 9.7% of the total fingerling operations used one or both vaccines; 12.3% of the total industry fry production was vaccinated against ESC, and 17.0% was vaccinated against columnaris disease. Of the producers who grew food-sized catfish to harvest, 6.7% used vaccinated catfish. The farms that did not use vaccinated fish for grow out had a mean size of 63.4 water surface hectares (156.6 water surface acres). The operations that used vaccinated fish were larger (mean size = 206.6 water surface hectares, or 510.6 water surface acres). The producers that stocked ESC-vaccinated fish for grow out represented 19.0% of the total water surface area of food fish production; producers that stocked columnaris-vaccinated fish represented 16.6% of the total area. Of the producers that stocked ESC-vaccinated catfish, 41.9% thought that survival was better in vaccinated fish than in unvaccinated fish; of the producers that stocked columnaris-vaccinated catfish, 46.2% thought that vaccinated fish displayed better survival. However, 37.5% of producers that used the ESC vaccine and 39.7% of producers that used the columnaris vaccine did not know whether vaccination improved survival rates. When all producers were asked about their expectations regarding the percentage of vaccinated fish that would be protected from disease, 52.4% responded that they expected 100% of their fish to be protected. More producer information about reasonable expectations regarding vaccine efficacy, the conditions under which immunosuppression and vaccine failure can occur, and assessment of vaccine performance may result in increased use of vaccination as a tool for the catfish industry. PMID- 22779212 TI - Preliminary assessment of dietary mannanoligosaccharides on growth performance and health status of gilthead seabream Sparus auratus. AB - A feeding trial was performed to assess the potential beneficial effect of two levels of mannanoligosaccarides (MOS) on the growth performance, feed utilization, hematological parameters, and liver histopathology of gilthead seabream Sparus auratus (also known as gilthead bream). Mannanoligosaccarides were added at the rates of 2 and 4 g/kg to a fish-meal-based control diet, and each diet was given (twice daily [midmorning and midafternoon] to apparent satiation) to triplicate groups of gilthead seabream growers (mean weight = approximately 170 g) in sea cages. The trial lasted 12 weeks, and the average ambient water temperature ranged from 19.6 degrees C to 24.7 degrees C during the experimental period. At the end of the experiment, fish attained market size (350 450 g) and their health status was evaluated by blood analysis and liver histology. There were no differences in survival rates among fish fed experimental diets. However, there were significant improvements in both growth and feed utilization among fish fed diets supplemented with MOS. Hemoglobin (Hb) and hematocrit (Ht) levels and erythrocyte, leukocyte, and thrombocyte (Thr) counts were unaffected by any dietary MOS. The levels of Hb (g/dL; mean +/- SD) and Ht (%; mean +/- SD) were 11.0 +/- 2.5 and 45.6 +/- 6.7 for the control group, 11.1 +/- 1.7 and 39.3 +/- 8.0 for the 2-g/kg group, and 11.2 +/- 1.9 and 40.2 +/- 8.4 for the 4-g/kg group. The mean Thr count ranged from 47.6 to 53.8 x 10(3)/mm3. Despite the apparently higher Thr counts for fish fed diets supplemented with MOS, these differences were not significant. Moreover, no histopathological differences were observed in liver tissue cross sections between control and treatment groups. These results suggest that supplementation of diets with MOS had no significant effects on general fish health. PMID- 22779213 TI - Susceptibility of Pacific herring to viral hemorrhagic septicemia is influenced by diet. AB - Groups of specific-pathogen-free Pacific herring Clupea pallasii were highly susceptible to infection by viral hemorrhagic septicemia virus (VHSV); however, the level of mortality was influenced by diet during the 40-71 d before, during, and after the first exposure to the virus. Cumulative mortality was highest among the herring maintained on an experimental soy-based pellet, intermediate among those maintained on a commercially available fish-meal-based pellet, and lowest among those maintained on a second commercially available fish-meal-based pellet containing beta-glucans. Additionally, the herring maintained on the experimental soy-based feed demonstrated less growth than those on the commercially available feeds. The results indicate the importance of standardizing diet during empirical determinations of disease susceptibility and provide insights into the risk factors affecting VHS susceptibility in wild populations. PMID- 22779214 TI - Effects of media ingredient substitution and comparison of growth of Flavobacterium psychrophilum among four media. AB - The etiological agent of bacterial cold-water disease, Flavobacterium psychrophilum, can cause significant losses of salmonid fishes in aquaculture facilities. Few studies describing the value of media components on the growth of F. psychrophilum are available in the literature. We therefore conducted a study that began with the standard enriched Anacker-Ordal broth (EAO) and over the course of multiple iterations evaluated the effects of various media supplements by adding or subtracting them from the base EAO medium. Different media formulations were made, and samples were removed from each broth formulation every 24 h for 72 h. From those samples we determined bacterial density by measuring absorbance values with a spectrophotometer. The medium with the highest absorbance value from one iteration was used as the base medium in the next iteration. Using this iterative approach, we determined that sodium acetate, calcium chloride, and magnesium sulfate inhibit growth and that maltose has no effect on the proliferation of the bacterium. The addition of skimmed milk (0.2%) and horse serum (1%) appears to provide a slight improvement in bacterial proliferation. Variations in agar concentration had no effect on the growth of the bacterium. Even though the addition and removal of some ingredients increased the mean absorbance values, the benefit of these substitutions was not significant. Even so, we found that the growth of F. psychrophilum in EAO was better than that in two other widely used media: tryptone-yeast extract salts and maltose infused tryptone-yeast extract salts. PMID- 22779215 TI - Comparison of the clinical efficacy in reducing dentin hypersensitivity of a new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm sodium monofluorophosphate to a commercially available toothpaste containing 1000 ppm sodium monofluorophosphate: an eight-week clinical trial on adults in New Delhi, India. AB - OBJECTIVE: This clinical study evaluated relief from dentin hypersensitivity among subjects who brushed their teeth with a new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm fluoride as sodium monofluorophosphate (MFP) to subjects who brushed with a commercially available dentifrice containing 1000 ppm MFP over an eight-week period. METHODS: Adult subjects from the New Delhi, India area, with two teeth that exhibited dentin hypersensitivity, both to tactile stimulation using the Yeaple Probe and to stimulation using an air blast delivered by a standard dental unit syringe, were screened for study enrollment. Qualifying subjects were randomly assigned one of the study dentifrices and instructed to brush their teeth for one minute, twice daily (morning and evening) with the provided dentifrice. Follow-up examinations for dentin hypersensitivity were conducted after two, four, and eight weeks of product use. RESULTS: Subjects provided with the new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm MFP exhibited statistically significantly (p < 0.05) greater reductions in dentin hypersensitivity in response to tactile (81.9%, 90.5%, and 116.7%) and air blast (39.5%, 56.7%, and 76.7%) stimuli than subjects assigned the 1000 ppm MFP dentifrice after two, four, and eight weeks, respectively. CONCLUSION: The use of a new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm MFP provides superior efficacy in reducing dentin hypersensitivity (p < 0.05) than a control dentifrice containing 1000 ppm MFP alone after two, four, and eight weeks of use. PMID- 22779216 TI - Comparison of the clinical efficacy of a new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm fluoride to a commercially available sensitive toothpaste containing 2% potassium ion on dentin hypersensitivity: a randomized clinical trial. AB - OBJECTIVE: This clinical study was designed to compare dentin hypersensitivity relief among subjects who brushed their teeth with a new toothpaste containing 8.0% arginine, calcium carbonate, and 1000 ppm fluoride as sodium monofluorophosphate (MFP) to subjects who brushed with a commercially available dentifrice containing 2% potassium ion as potassium nitrate over an eight-week period. METHODS: Adult male and female subjects from the New Delhi, India area were required to present two teeth that exhibited dentin hypersensitivity, both to tactile stimulation using the Yeaple Probe and to air blast stimulation delivered by a standard dental unit syringe. After an examination of the oral soft and hard tissues, qualifying subjects were randomly assigned one of the study dentifrices and a soft-bristled toothbrush, and were instructed to brush their teeth for one minute, twice daily (morning and evening), using only the toothbrush and dentifrice provided. No other oral hygiene practices were permitted over the course of the study. After two, four, and eight weeks of product use, subjects returned to the dental clinic for follow-up examinations of tactile and air blast sensitivity of the baseline-designated hypersensitive teeth. Examinations of the oral soft and hard tissues were also performed at these follow-up visits. RESULTS: Subjects who brushed with the new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm MFP exhibited statistically significant reductions (p < 0.05) in dentin hypersensitivity in response to tactile (36.2%, 33.1%, and 29.7%) and air blast (16.4%, 31.1%, 58.8%) stimuli when compared to the subjects who brushed with the 2% potassium ion as potassium nitrate dentifrice after two, four, and eight weeks, respectively. CONCLUSION: The use ofa new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm MFP provides greater efficacy in reducing dentin hypersensitivity when compared to a dentifrice containing 2% potassium ion, as potassium nitrate, after two, four, and eight weeks of product use. PMID- 22779217 TI - Custom tray application of peroxide gel as an adjunct to scaling and root planing in the treatment of periodontitis: a randomized, controlled three-month clinical trial. AB - OBJECTIVE: Periodontitis is an inflammatory condition of the supporting dental tissues that is normally treated by mechanical removal of the subgingival biofilm. This mechanical treatment, generally known as scaling and root planing (SRP), is not entirely effective, and various adjunctive therapies have been investigated to improve the clinical outcome. This study evaluated the clinical effects of SRP alone or combined with local administration of hydrogen peroxide gel using customized trays in the treatment of subjects with chronic periodontitis. METHODS: An examiner-blind clinical trial was conducted among 30 subjects with moderate to advanced periodontitis, who were randomized to SRP alone or SRP combined with a prescription custom-tray application (Perio Tray) of 1.7% hydrogen peroxide gel (Perio Gel) for a period of three months. Following impressions for the test group, all subjects brushed twice daily with a regular dentifrice and toothbrush for a four-week acclimation phase to standardize oral conditions (while trays were fabricated) prior to initiating the treatment phase. Clinical assessments, i.e., pocket probing depth (PPD) and bleeding index (BI), were conducted at baseline and after two, five, and 13 weeks of peroxide applications; SRP was performed three weeks after baseline. Clinical variables were compared by ANOVA and paired t-tests after each treatment interval. RESULTS: A total of 13 test and 15 control subjects completed the study. After two weeks of peroxide gel use prior to SRP, mean whole-mouth PPD was unchanged for the control group, but significantly decreased 0.21 mm in the test group. Two weeks following SRP, mean PPD decreased from baseline by 0.17 mm for the control group and 0.65 mm for the test group. Ten weeks following SRP, mean PPD decreases were 0.13 mm for the control group and 0.77 mm for the test group. After two weeks of peroxide use prior to SRP, mean whole-mouth BI decreased 0.03 (from 15% to 12%) for the control and 0.14 (from 23% to 9%) for the test group. Two weeks after SRP, the mean whole-mouth BI score decreased 0.05 from baseline (15% to 10%) for the control and 0.17 (23% to 6%) for the test group. Ten weeks after SRP, there was no change from baseline for the control group, but BI was 0.14 lower (23% to 9%) for the test group. Further analysis showed the same statistical relationship between groups for PPD assessments of deeper pockets. For pockets > or =6 mm at baseline, mean PPD decreased by 0.04 mm for the control compared to 0.48 mm for the test group after two weeks of peroxide gel use and prior to SRP. Two weeks after SRP, mean PPD decreased from baseline by 0.60 mm for the control and 1.40 mm for the test group, and 10 weeks after SRP by 0.58 mm for the control and 1.57 mm for the test group. All reductions cited above for the test group were statistically significantly different from the control group for both PPD and BI. CONCLUSION: The adjunctive use over three months of 1.7% hydrogen peroxide gel, locally administered using prescription customized trays in the treatment of subjects with moderate to advanced periodontitis, demonstrated statistically significant clinical improvements in pocket depths and bleeding when compared with SRP alone. PMID- 22779218 TI - The addition of a water flosser to power tooth brushing: effect on bleeding, gingivitis, and plaque. AB - OBJECTIVE: The primary objective of this study was to compare the effectiveness of a water flosser plus sonic toothbrush to a sonic toothbrush alone on the reduction of bleeding, gingivitis, and plaque. The secondary objective was to compare the effectiveness of different sonic toothbrushes on bleeding, gingivitis, and plaque. METHODS: One-hundred and thirty-nine subjects completed this randomized, four-week, single-masked, parallel clinical study. Subjects were assigned to one of four groups: Waterpik Complete Care, which is a combination of a water flosser plus power toothbrush (WFS); Sensonic Professional Plus Toothbrush (SPP); Sonicare FlexCare toothbrush (SF); or an Oral-B Indicator manual toothbrush (MT). Subjects were provided written and verbal instructions for all power products at baseline, and instructions were reviewed at the two week visit. Data were evaluated for whole mouth, facial, and lingual surfaces for bleeding on probing (BOP) and gingivitis (MGI). Plaque data were evaluated for whole mouth, lingual, facial, approximal, and marginal areas of the tooth using the Rustogi Modification of the Navy Plaque Index (RMNPI). Data were recorded at baseline (BL), two weeks (W2), and four weeks (W4). RESULTS: All groups showed a significant reduction from BL in BOP, MGI, and RMNPI for all areas measured at the W2 and W4 visits (p < 0.001). The reduction of BOP was significantly higher for the WFS group than the other three groups at W2 and W4 for all areas measured (p < 0.001 for all, except p = 0.007 at W2 and p = 0.008 for W4 lingual comparison to SPP). The WFS group was 34% more effective than the SPP group, 70% more effective than the SF group, and 1.59 times more effective than the MT group for whole mouth bleeding scores (p < 0.001) at W4. The reduction of MGI was significantly higher for the WFS group; 23% more effective than SPP, 48% more effective than SF, and 1.35 times more effective than MT for whole mouth (p <0.001) at W4. The reduction of MGI was significantly higher for WFS than the SF and MT for facial and lingual surfaces, and more effective than the SPP for facial surfaces (p < 0.001) at W4. The WFS group showed significantly better reductions for plaque than the SF and MT groups for whole mouth, facial, lingual, approximal, and marginal areas at W4 (p < 0.001; SF facial p = 0.025). For plaque reduction, the WFS was significantly better than the SPP for whole mouth (p = 0.003) and comparable for all other areas and surfaces at W4. The WFS was 52% more effective for whole mouth, 31% for facial, 77% for lingual, 1.22 times for approximal, and 1.67 times for marginal areas compared to the SF for reducing plaque scores at W4 (p < 0.001; SF facial p = 0.025). The SPP had significantly higher reductions than the SF for whole mouth and lingual BOP and MGI scores, and whole mouth, approximal, marginal, and lingual areas for plaque at W4. CONCLUSION: The Waterpik Complete Care is significantly more effective than the Sonicare FlexCare toothbrush for reducing gingival bleeding, gingivitis, and plaque. The Sensonic Professional Plus Toothbrush is significantly more effective than the Sonicare Flex-Care for reducing gingival bleeding, gingivitis, and plaque. PMID- 22779219 TI - Localized reduction of gingival inflammation using site-specific therapy with a topical gingival patch. AB - METHODS: Sites of inflammation were identified on subjects with moderate-to severe chronic periodontitis, and were allocated to either patch placement or untreated controls, both for 24 hours. Conventional treatment with scaling and root planing was postponed during the study period. Inflammation was evaluated measuring neutrophilic activity using gingival crevicular fluid (GCF) beta glucuronidase (b-glu) levels, and clinical response was evaluated using the gingival index (GI). RESULTS: A total of 26 patients were recruited and 36 sites examined, with 22 sites on which the patch was placed and 14 controls. GCF b-glu levels at 24 hours were reduced following patch placement, significantly more so than with controls (17/22 vs. 3/14 sites, respectively; p = 0.002). The patch placement resulted in a significant reduction in mean b-glu levels (-2.52 +/- 1.62), with a reduction from baseline of 29.7%. This compared to untreated controls, for whom the mean b-glu levels and percent change from baseline increased (2.14 +/- 0.89 and 33%, respectively). At 24 hours, GI response rate for treated sites was better than for control sites (18/21 vs. 7/14; p = 0.053). No adverse events were reported in either group. CONCLUSION: This pilot study indicates that a topical gingival patch promotes reduction of gingival inflammation. Further clinical testing of this novel treatment of gingival inflammation is warranted. PMID- 22779220 TI - Effect of an 8.0% arginine and calcium carbonate desensitizing toothpaste on shear dentin bond strength. AB - OBJECTIVE: The objective of this study was to determine the effect of an 8.0% arginine and calcium carbonate desensitizing toothpaste (Colgate Sensitive Pro Relief) on shear bond strength of composites to bovine incisor dentin. METHODS: Bovine incisors were sectioned and prepared into 27 dentin specimens. The experimental group had 13 specimens treated for 10 sessions of two-minute brushing with an 8.0% arginine and calcium carbonate desensitizing toothpaste, followed by a 30-second agitated water wash. The control group had 14 specimens treated with flour of pumice only. Each specimen was dried, etched with 35% phosphoric acid for 15 seconds, and washed clean. A bonding agent was applied and polymerized. A 2.38 mm diameter column of Filtek Supreme A2 was bonded to the surface and polymerized as per manufacturer's instructions. Specimens were stored in water for at least 48 hours, subjected to a shear force at a crosshead speed of 0.5 mm/minute on an Instron mechanical testing device, and force at failure was recorded. A one-sided t-test was used to evaluate significant differences among the groups as measured by mean shear strength. RESULTS: Mean shear force was 19.6 +/- 9.4 (SD) for the experimental group and 15.4 +/- 6.0 for the control group with p = 0.0291. CONCLUSION: No significant differences were found for bond strength to dentin treated with an 8.0% arginine and calcium carbonate desensitizing toothpaste or pumice. Dentists can still achieve optimal dentin bonding results if a patient is using Colgate Sensitive Pro-Relief to manage dentin hypersensitivity. PMID- 22779221 TI - Needle biopsy for hepatic vitamin A levels in lions (Panthera leo). AB - Hypovitaminosis A (HA)-related skull malformations resulting in neurologic abnormalities and death have been, and still are, reported in captive lions (Panthera leo) worldwide. Liver vitamin A (VA) concentration is the most reliable indicator of animals' VA status, and its assessment is essential in prevention and treatment of HA in lions. A percutaneous needle liver biopsy using high performance liquid chromatography ultraviolet retinoid analysis for VA concentration measurement was validated. It was first assessed in vitro using chicken liver. Later, the safety and feasibility of ultrasound-guided percutaneous needle liver biopsy was assessed in living lions. Hepatic VA concentrations in lion liver were measured using the above laboratory method. Mean chicken hepatic VA concentration in needle biopsy (NB) and wedge biopsy (WB) of the same liver lobes were 108.66 and 60.89 microg/g wet tissue, respectively, and were significantly (P = 0.03) correlated (r = 0.74). The calculated linear regression for predicting VA concentration in WB using NB VA for chicken liver was 25.194 + 0.3234x NB (microg/g). Four ultrasound-guided percutaneous needle liver biopsies were obtained from each of the four lions under general anesthesia. Mean hepatic VA concentration was 8.25 microg/g wet tissue (range 1.43-25.29 microg/g). Mean serum VA concentration, measured in these four lions was 1,011.1 nmol/L with a standard deviation of 337.91 nmol/L (range 590.26 1,077.2 nmol/L). The lions recovered uneventfully, and no complications were observed during a 4-yr follow-up period. In conclusion, the percutaneous needle liver biopsy technique is a reliable, practical, safe tool for obtaining liver tissue samples antemortem for assessment of the VA status in lions and can be used in future studies. PMID- 22779222 TI - Development of a minimum-anesthetic-concentration depression model to study the effects of various analgesics in goldfish (Carassius auratus). AB - Teleost fish demonstrate the neurophysiologic capacity to experience pain and analgesia. A common model for assessing analgesic effect is the reduction of minimum anesthetic concentration (MAC). The present study adapted the model of MAC depression to evaluate the analgesic effects of morphine, butorphanol, medetomidine, and ketoprofen in goldfish (Carassius auratus). MAC was determined by an up-down method of sequential population sampling, anesthetizing fish with tricaine methanesulfonate (MS-222) in concentration increments of 10 parts per million (ppm), and using intramuscular needle insertion as a supramaximal noxious stimulus. Baseline MAC was determined in triplicate at the beginning (MACi) and conclusion (MACe) of the experiment (approximately 60 days). For drug trials, MAC was redetermined 1 hr after administration of morphine (10, 20, 40 mg/kg i.m.), butorphanol (0.1, 0.2, 0.4 mg/kg i.m.), medetomidine (0.01, 0.015, 0.025 mg/kg i.m.), ketoprofen (0.5, 1.0, 2.0 mg/kg i.m.), or saline control. Each drug/dose was tested in random order with a > 6-day washout period. MACi and MACf were 163 and 182 ppm, respectively, and were significantly different from each other (P = 0.02). All doses of morphine and ketoprofen decreased MAC below MACi. The highest dose of medetomidine decreased MAC below MACi. The lowest dose of butorphanol decreased MAC below MACi, but higher doses increased MAC above MACf. The authors conclude that MAC determination in fish using MS-222 was feasible and reproducible in the short term. The fact that MAC increased over time and/or exposure may limit the usefulness of MS-222 in MAC depression studies. Morphine and ketoprofen decrease anesthetic needs in goldfish and may provide analgesia. PMID- 22779223 TI - Serologic survey for Leptospira spp. in captive neotropical felids in Foz do Iguacu, Parana, Brazil. AB - Leptospirosis is a bacterial zoonosis of worldwide distribution and is endemic in tropical countries, where rodents and other wild mammals are abundant and may act as reservoirs. Leptospirosis has become a concern in captive wild animals, due mostly to their exposure to contaminated urine or environment. Although domestic cats (Felis catus) have been reported refractory to leptospirosis, serology and disease in captive wild felids is still unclear. In this study 57 adult, clinically healthy felids, including 1 Geoffroy's cat (Leopardus geoffroyi), 3 jaguarundis (Puma yagouaroundi), 17 margays (Leopardus wiedii), 22 little spotted cats (Leopardus tigrinus), and 14 ocelots (Leopardus pardalis) kept in captivity at the Sanctuary at the Itaipu Binacional hydroelectric power plant (Bela Vista Biological Sanctuary), Foz do Iguacu City, Parana State, Brazil, were serologically surveyed for the presence of antibodies against 28 serovars of Leptospira spp. by microagglutination test (MAT). Two animals (3.5%) were seropositive: one male ocelot to the serovar Cynopteri (titer 100) and one female margay to Autumnalis (100) and Butembo (200). The captive-born, 5-yr-old ocelot had been solitary housed in an individual cage. The approximately 21-yr-old wild caught margay was also kept individually. None of the tested animals showed signs ofleptospirosis. During a study conducted 4 yr previously in the same facility, this particular margay also tested positive for the same two serovars, among others. The present study indicates that the felids tested for Leptospira spp. by MAT were exposed to serovars, but did not demonstrate clinical signs of disease. Comparison with a previous study suggests that serovar titers may vary over time and that leptospirosis dynamics remains unclear in wild felids. PMID- 22779224 TI - Determination of reference values for intraocular pressure and Schirmer tear test in clinically normal ostriches (Struthio camelus). AB - The purpose of this study was to establish normal physiologic reference values for intraocular pressure (IOP) and Schirmer tear test (STT) results in clinically normal ostriches (Struthio camelus). Twenty ostriches of both sexes, 10 juveniles (1.5-2 yr of age) and 10 adults, were included in this study. Complete ophthalmic examination was performed prior to this investigation. STT was performed by inserting a standard sterile STT strip over the ventral lid margin into the ventral conjunctival sac for 60 sec. Following the STT, IOP was measured using applanation tonometry with the Tono-Pen Vet tonometer after topical instillation of one drop of 0.5% proparacaine ophthalmic solution. The mean +/- SD and range of Tono-Pen readings of IOP for all birds was 18.8 +/- 3.5, with a range of 12 24. Mean IOP in juvenile ostriches was 19.7 +/- 3.6. Mean IOP in adult ostriches was 16.9 +/- 2.9. There was no statistically significant difference between young and adult birds (P = 0.07). The mean STT values in the present study were 16.3 +/ 2.5 mm/1 min when measurements from both eyes were averaged. Mean STT in juvenile and adult ostriches was 15.4 +/- 1.8 and 17.2 +/- 2.9 mm/1 min, respectively. There was no statistically significant difference between young and adult birds (P = 0.11). No statistically significant differences between genders were found for any of the results (P > or = 0.41). In conclusion, this study provides normal reference range values for STT and IOP in clinically healthy ostriches. PMID- 22779225 TI - Risk factors associated with perianesthetic mortality of stranded free-ranging California sea lions (Zalophus californianus) undergoing rehabilitation. AB - The objective of this study was to identify risk factors associated with perianesthetic mortality of stranded free-ranging California sea lions (Zalophus californianus) undergoing rehabilitation. Hospital records of California sea lions that underwent heavy sedation or general anesthesia from 2004 through 2008 were reviewed, including records from 419 anesthetic events. Procedures that resulted in death during or in the subsequent 72 hr of anesthesia were classified as cases (n = 15). Procedures in which the animal survived were classified as controls (n = 334). Procedures that resulted in euthanasia (n = 70) were removed from subsequent analysis. The following risk factors were reviewed: gender, age class, health status, duration of anesthetic period, atropine premedication, induction protocols, maintenance protocols, and history of prior anesthesia. The prevalence of fatalities during anesthesia was 3.4% (n = 12) over the 5-yr period. With the inclusion of animals that died within 72 hr after anesthesia, the total mortality prevalence rose to 4.3% (n = 15). The most common time of death was during anesthetic maintenance. Health status was the single best predictor of anesthetic outcome, and sea lions premedicated with atropine had increased odds of anesthetic-related death. PMID- 22779226 TI - Hematology and serum biochemistry of free-ranging nutria (Myocastor coypus). AB - Information on reference blood values in the literature is lacking for many wild rodents. In this study, comprehensive reference intervals (RIs) for a wide range of analytes from 101 healthy free-ranging nutria were determined. Animals were captured in Buenos Aires, Argentina (37degrees 50'S, 57 degrees 34'W), and southward (38 degrees 60'S, 58 degrees 23'W), encompassing major biotopes of agricultural pampas with dunes and grassland steppes on the east coast. Traps were set at locations with high-density nutria populations (i.e., those areas that showed signs of movement, territorial marking, or feeding activities). Although the small sample size limits the interpretation of these findings, RIs were determined by a robust method using the central 95th percentile. In nutria, the RI range varied greatly for the leukocyte differentials, with mature neutrophils: 3,907-5,544/mmicrol for females and 3,744-5,900/microl for males; band neutrophils: 0-10/ll for females and 3-18/microl for males; lymphocytes: 4,213 5,940/microl for both sexes combined; monocytes: 165-402/microl for both sexes combined; eosinophils: 13-91/microl for females and 108-165/microl for males; and basophils: 0-87/microl for both sexes combined. Platelet concentration was 543-727 x 10(9)/L for both sexes combined. There was also a wide RI range for biochemistry values for some enzymes, such as alkaline phosphatase: 200-399 IU/L for both sexes combined; cholinesterase: 762-1,407 IU/L for females and 763-1,284 IU/L for males; creatine kinase: 182-552 IU/L for females and 162-451 IU/L for males; amylase: 853-1,865 IU/L for females and 779-1,293 IU/L for males; and glucose concentration 120.2-180.6 mg/dl for both sexes combined. Conversely, there was not a wide pooled RI range for calcium: 7.0-11.2 mg/dl; phosphorous: 6.1-9.3 mg/dl; sodium: 133.0-159.0 mEq/L; potassium: 3.0-8.2 mEq/L; chloride: 101.4-143.0 mEq/L; and urea: 11.3-36.8 mg/dl. The red blood cell indices had a narrow range, with mean corpuscular volume: 84.0 -102.5 fl and mean corpuscular hemoglobin concentration: 18.2-28.8 g/dl, and which was most likely due to strict physiologic controls. The results from this study were similar to those previously reported for farmed nutria. PMID- 22779227 TI - Antibody response to vaccines for rhinotracheitis, caliciviral disease, panleukopenia, feline leukemia, and rabies in tigers (Panthera tigris) and lions (Panthera leo). AB - This article presents the results of a study of captive tigers (Panthera tigris) and lions (Panthera leo) vaccinated with a recombinant vaccine against feline leukemia virus; an inactivated adjuvanted vaccine against rabies virus; and a multivalent modified live vaccine against feline herpesvirus, calicivirus, and panleukopenia virus. The aim of the study was to assess the immune response and safety of the vaccines and to compare the effects of the administration of single (1 ml) and double (2 ml) doses. The animals were separated into two groups and received either single or double doses of vaccines, followed by blood collection for serologic response for 400 days. No serious adverse event was observed, with the exception of abortion in one lioness, potentially caused by the incorrect use of the feline panleukopenia virus modified live vaccine. There was no significant difference between single and double doses for all vaccines. The recombinant vaccine against feline leukemia virus did not induce any serologic response. The vaccines against rabies and feline herpesvirus induced a significant immune response in the tigers and lions. The vaccine against calicivirus did not induce a significant increase in antibody titers in either tigers or lions. The vaccine against feline panleukopenia virus induced a significant immune response in tigers but not in lions. This report demonstrates the value of antibody titer determination after vaccination of nondomestic felids. PMID- 22779228 TI - Sonographic evaluation of thyroid morphology during the normal estrous cycle in the Indo-Pacific bottlenose dolphin (Tursiops aduncus). AB - Physiologic changes occurring in the thyroid in response to the estrous cycle have been noted in companion animals. However, in bottlenose dolphins, the influence of different reproductive states on thyroid morphology remains unclear. Sonography was used to evaluate the variations of thyroid morphology for nine consecutive estrous cycles of four sexually mature, female Indo-Pacific bottlenose dolphins (Tursiops aduncus). The estrous cycle was divided into two phases for evaluation: the follicular and luteal phases. To compare changes associated with sex, thyroid volumes were measured in the different phases during the estrous cycle of female dolphins and were compared to the ultrasound examinations of the four male dolphins measured over a 2-mo period. In males, there was no significant difference in thyroid volume during the study period (P > 0.05). The thyroid volume measured in combining all estrous cycle phases of the female dolphins was significantly larger than that measured in the male dolphins (P < 0.05). A difference in thyroid volume during the estrous cycle was observed, with the thyroid volume during the follicular phase significantly smaller (P < 0.05) than that of the luteal phase, and is possibly related to the influence of female sex steroids. Thyroid volume variability during estrus should, therefore, be taken into account when examining the thyroid gland of female dolphins. PMID- 22779229 TI - Thoracic auscultation in captive bottlenose dolphins (Tursiops truncatus), California sea lions (Zalophus californianus), and South African fur seals (Arctocephalus pusillus) with an electronic stethoscope. AB - Thoracic auscultation is an important diagnostic method used in cases of suspected pulmonary disease in many species, as respiratory sounds contain significant information on the physiology and pathology of the lungs and upper airways. Respiratory diseases are frequent in marine mammals and are often listed as one of their main causes of death. The aim of this study was to investigate and report baseline parameters for the electronic-mediated thoracic auscultation of one cetacean species and two pinniped species in captivity. Respiratory sounds from 20 captive bottlenose dolphins (Tursiops truncatus), 6 California sea lions (Zalophus californianus), and 5 South African fur seals (Arctocephalus pusillus) were recorded with an electronic stethoscope. The sounds were analyzed for duration of the respiratory cycle, adventitious sounds, and peak frequencies of recorded sounds during expiration and inspiration as well as for sound intensity as reflected by waveform amplitude during the respiratory cycle. In respiratory cycles of the bottlenose dolphins' expiring "on command," the duration of the expiration was significantly shorter than the duration of the inspiration. In the examined pinnipeds of this study, there was no clear pattern concerning the duration of one breathing phase: Adventitious sounds were detected most often in bottlenose dolphins that were expiring on command and could be compared with "forced expiratory wheezes" in humans. This is the first report of forced expiratory wheezes in bottlenose dolphins; they can easily be misinterpreted as pathologic respiratory sounds. The peak frequencies of the respiratory sounds reached over 2,000 Hz in bottlenose dolphins and over 1,000 Hz in California sea lions and South African fur seals, but the variation of the frequency spectra was very high in all animals. To the authors' knowledge, this is the first systematic analysis of respiratory sounds of bottlenose dolphins and two species of pinnipeds. PMID- 22779230 TI - Validation of a fecal glucocorticoid metabolite assay for collared peccaries (Pecari tajacu). AB - The possibility of assessing endogenous adrenal activity in the collared peccary (Pecari tajacu) was tested by using an adrenocorticotropic hormone (ACTH) challenge in a fecal glucocorticoid metabolite (FGM) assay. Feces were collected from 12 captive adult male peccaries beginning 48 hr prior to challenge; six of these animals received the challenge as an ACTH injection and the other six were injected with saline solution. Feces collection ended 120 hr after injections. As a control, feces were collected for eight consecutive days from another six adult male peccaries that remained in their original mixed-sex herds in semiconfined paddocks. All feces samples were freeze-dried, extracted by an ethanol vortex method, and assayed for glucocorticoids by means of an enzyme immunoassay. FGM concentrations were compared between the treatments by a repeated measures analysis of variance (ANOVA) followed by a post hoc Tukey test. The assay is reliable but, instead of the usual proportion of 1:50 in ethanol (fecal mass:solvent), 1:10 is recommended for best extraction of FGM. Baseline FGM concentrations were similar among the ACTH, saline, and control treatments (29.7 +/- 11.2 ng/g(-1) dry feces) during the 48 hr before the challenge. The ACTH group reached an FGM excretion peak at 24 hr post-treatment, followed by a decline, while in the control and saline groups FGM levels remained relatively constant. Therefore, the fecal glucocorticoid metabolite assay reflects endogenous adrenal activity in the collared peccary and is a powerful tool for noninvasive stress monitoring in peccaries. PMID- 22779231 TI - Clinical implications of infection with a novel metastrongyloid species in the red panda (Ailurus fulgens). AB - In a recent survey, 30% of the European red panda (Ailurus fulgens) population was found to be infected with a newly discovered metastrongyloid nematode. In a following prospective study, four naturally infected captive-bred red pandas infected with this parasite were examined and compared with two uninfected control animals. On clinical examination, no abnormalities were detected with respect to vital parameters and cardiovascular system in all six examined animals. Similarly, few and nonspecific changes were recorded on serum biochemistry. No changes on pulmonary pattern were noted on thoracic radiographs. Vertebral heart scores were between 7.2 to 8.6, and no difference was noted between infected and control animals. Two animals had slightly prolonged clotting time and reaction time on thromboelastography but not likely to be of clinical relevance. In conclusion, infection with the newly identified metastrongyloid nematode in the red pandas seems to have little or no clinical importance. PMID- 22779232 TI - Evaluation of cyclooxygenase protein expression in traumatized versus normal tissues from eastern box turtles (Terrapene carolina carolina). AB - This pilot study was designed to determine whether cyclooxygenase (COX)-1, COX-2, or both are expressed in normal turtle tissues and whether level of expression changes when tissue becomes inflamed. Five eastern box turtles, Terrapene carolina carolina, that either died or were euthanatized due to disease or injuries were used for this work. Tissues were obtained from the five turtles. Western blot analysis was used to evaluate tissues for COX-1 and COX-2 proteins. Densiometric analysis was used to compare Western blot bands within each turtle. COX-1 and COX-2 were found in the liver, kidney, grossly normal muscle, and grossly traumatized (inflamed) muscle of all study turtles. In all cases, COX-1 and COX-2 proteins were increased in traumatized muscle over grossly normal nontraumatized muscle. The highest levels of COX-1 and COX-2 proteins were found in kidney and liver. There was no statistical difference between the amount of COX-1 protein in liver and kidney, but traumatized muscle compared with grossly normal muscle had significantly greater COX-1 but not COX 2 protein concentrations. There was no statistical difference between the amount of COX-2 protein in liver and kidney. Traumatized muscle expressed nonstatistically significant greater amounts of COX-2 compared with grossly normal muscle. COX-1 and COX-2 proteins are expressed in turtle tissues, and both isoforms are upregulated during inflammation of muscle tissue. Traditional nonsteroidal anti inflammatory drugs (NSAIDs) that block both COX isoforms might be more efficacious than COX-2-selective drugs. This work suggests that NSAIDs should be evaluated for potential liver and kidney toxicity in turtles. PMID- 22779233 TI - Altrenogest and progesterone therapy during pregnancy in bottlenose dolphins (Tursiops truncatus) with progesterone insufficiency. AB - Progesterone production is essential for growth and development of the conceptus during pregnancy. Abnormal development of the corpus luteum (CL) after conception can result in early embryonic loss or fetal abortion. Routine monitoring of bottlenose dolphin (Tursiops truncatus) pregnancy after artificial insemination or natural conception with ultrasonography and serum progesterone determination has allowed for the establishment of expected fetal growth rates and hormone concentrations. Using these monitoring techniques, we revealed four pregnant dolphins (12-24 yr old) with abnormally low progesterone production indicative of luteal insufficiency. Once diagnosed, animals were placed on altrenogest (0.044 0.088 mg/kg once daily) alone or with oral progesterone (50-200 mg twice daily). Doses of hormone were increased or decreased in each animal based on how fetal skull biparietal and thoracic growth rates compared with published normal values. Hormones were withdrawn starting from day 358 of gestation in animals 1 and 2, with labor occurring 6 and 7 days after withdrawal and at 376 and 373 days of gestation, respectively. Both deliveries were dystocic, with each calf requiring manual extraction and fetotomy for calf 1. The fetuses in animals 3 and 4 died at 348 and 390 days of gestation, respectively. Induction of labor was attempted in both animals, after fetal death, by using a combination of rapid progesterone withdrawal and steroid and prostaglandin F2alpha administration. The calf of animal 4 had to be removed with manual cervical dilation and fetotomy All adult females survived the procedures. These data provide the first in vivo evidence that the CL is the primary source of progesterone throughout pregnancy in the bottlenose dolphin. Until further characterization of hormones required during pregnancy and at parturition has been accomplished, the exogenous progestagen supplementation protocol described here cannot be recommended for treatment of progesterone insufficiency in bottlenose dolphins. PMID- 22779234 TI - Pharmacokinetics of enrofloxacin after single dose oral and intravenous administration in the African penguin (Spheniscus demersus). AB - The pharmacokinetics of a single dose of enrofloxacin administered orally, both pilled and in fish, and i.v. to African penguins (Spheniscus demersus) at 15 mg/kg were determined. Plasma concentrations of enrofloxacin and its metabolite ciprofloxacin were measured via high-pressure liquid chromatography with mass spectrometry. An i.v. administration of enrofloxacin resulted in an extrapolated mean plasma concentration of 7.86 microg/ml at time zero. Plasma volume of distribution for i.v. administration was 3.00 L/kg, with a mean elimination half life of 13.67 hr and a mean total body clearance rate of 3.03 ml/min/kg. Oral administration of enrofloxacin achieved a mean maximum plasma concentration of4.38 microg/ml at 4.8 hr after administration when pilled, whereas mean maximum plasma concentration was 4.77 microg/ml at 1.59 hr after administration when given in fish. Mean terminal elimination half-life was 13.79 hr pilled and 11.93 hr when given in fish. Low concentrations of ciprofloxacin were detected after both oral and i.v. enrofloxacin administration. Enrofloxacin administered to African penguins at 15 mg/kg p.o.q. 24 hr, whether in fish or pilled, is expected to achieve the surrogate markers of efficacy for bacteria with a minimum inhibitory concentration of 0.5 microg/ml or less; however, clinical studies are needed to determine efficacy. PMID- 22779235 TI - Detection of antibodies to tuberculosis antigens in free-ranging lions (Panthera leo) infected with Mycobacterium bovis in Kruger National Park, South Africa. AB - Bovine tuberculosis (TB), caused by Mycobacterium bovis, has become established in Kruger National Park, South Africa, in the cape buffalo (Syncerus caffer) population and in other species. TB in prey species has resulted in infection and morbidity in the resident lion (Panthera leo) prides. The only validated live animal test currently available for lions is the intradermal tuberculin test. Because this test requires capture twice, 72 hr apart, of free-ranging lions to read results, it is logistically difficult to administer in a large ecosystem. Therefore, development of a rapid animal-side screening assay would be ideal in providing information for wildlife managers, veterinarians, and researchers working with free-living lion prides. This study reports preliminary descriptive results from an ongoing project evaluating two serologic tests for M. bovis (ElephantTB Stat-Pak and dual path platform VetTB). Disease status was determined by postmortem culture and presence of pathologic lesions in 14 free-ranging lions. Seropositivity was found to be associated with M. bovis infection. Extended field studies are underway to validate these rapid animal-side immunoassays for antemortem screening tests for TB in lions. PMID- 22779236 TI - A retrospective and prospective study of megaesophagus in the parma wallaby (Macropus parma) at the San Diego Zoo, California, USA. AB - At the San Diego Zoo (California, USA), 22 cases of megaesophagus were diagnosed in the parma wallaby (Macropus parma), yielding a prevalence of 21.1%. Parma wallabies often have no clinical signs until severe and chronic dilation of the esophagus is present. Clinical signs of advanced disease include weight loss, swelling of the cervical region, regurgitation without reswallowing of ingesta, short flight distance, depression, collapse, dyspnea, and sudden death. Retrospective and prospective studies at the San Diego Zoo and a multi institutional survey in the United States were used to try to determine the cause of megaesophagus. The retrospective study did not identify an etiology. The prospective study revealed megaesophagus and severely delayed esophageal transit time in eight of eight animals. Myasthenia gravis, lead toxicosis, toxoplasmosis, and thyroid disease were eliminated as possible causes. Of 286 living and dead parma wallabies surveyed at other institutions, three cases of esophageal diverticulum and one case of megaesophagus were reported. The cause of megaesophagus in parma wallabies was not determined. PMID- 22779237 TI - Chloramphenicol with fluid and electrolyte therapy cures terminally ill green tree frogs (Litoria caerulea) with chytridiomycosis. AB - Terminal changes in frogs infected with the amphibian fungal pathogen Batrachochytrium dendrobatidis (Bd) include epidermal degeneration leading to inhibited epidermal electrolyte transport, systemic electrolyte disturbances, and asystolic cardiac arrest. There are few reports of successful treatment of chytridiomycosis and none that include curing amphibians with severe disease. Three terminally ill green tree frogs (Litoria caerulea) with heavy Bd infections were cured using a combination of continuous shallow immersion in 20 mg/L chloramphenicol solution for 14 days, parenteral isotonic electrolyte fluid therapy for 6 days, and increased ambient temperature to 28 degrees C for 14 days. All terminally ill frogs recovered rapidly to normal activity levels and appetite within 5 days of commencing treatment. In contrast, five untreated terminally ill L. caerulea with heavy Bd infections died within 24-48 hr of becoming moribund. Subclinical infections in 15 experimentally infected L. caerulea were cured within 28 days by continuous shallow immersion in 20 mg/L chloramphenicol solution without adverse effects. This is the first known report of a clinical treatment protocol for curing terminally ill Bd-infected frogs. PMID- 22779238 TI - An outbreak of tuberculosis by Mycobacterium bovis in coatis (Nasua nasua). AB - Mycobacterium tuberculosis complex, which includes Mycobacterium bovis, infrequently causes severe or lethal disease in captive wildlife populations. A dead coati from a wildlife triage center showing pulmonary lesions compatible with tuberculosis had raised suspicion of a potential disease caused by mycobacteria species and was further investigated. Four native coatis (Nasua nasua) with suspected mycobacterial infection were sedated, and bronchoalveolar lavages and tuberculin skin tests (TSTs) were performed. All animals tested positive upon TST. Mycobacterial culturing, Ziehl-Neelsen staining, and genetic testing were performed on postmortem samples and the etiologic agent was identified as M. bovis. Molecular genetic identification using a polymerase chain reaction panel was crucial to achieving a definitive diagnosis. PMID- 22779239 TI - Primary feather follicle ablation in common pintails (Anas acuta acuta) and a white-faced whistling duck (Dendrocygna viduata). AB - Eight 1-yr-old common pintails (Anas acuta acuta) and one 2-yr-old white-faced whistling duck (Dendrocygna viduata) were presented for the persistence of primary flight feathers 1 yr after pinioning. The birds were housed outdoors in an open enclosure necessitating flight prevention. The birds were placed under general anesthesia, and a diode laser was used to ablate the primary feather follicles of the previously pinioned wing. Swelling was the most common side effect seen in seven out of nine treated birds. Other side effects included ulceration, hyperemia, edema, and serosanguinous discharge. All side effects were resolved by 12 wk postprocedure. Laser feather follicle ablation was successful in 28 of 40 (70%) of the treated common pintail feathers, and flight was not observed 7 mo following the procedure in any of these birds. Feather follicle ablation was successful in two of six (33%) of the treated white-faced whistling duck feathers, and the bird in question was observed flying 5 mo after the procedure. Primary feather follicle ablation with a diode laser was a successful method of flight prevention in common pintails but was not effective for a white faced whistling duck. PMID- 22779240 TI - Stifle osteochondritis dissecans in snow leopards (Uncia uncia). AB - Three snow leopard (Uncia uncia) cubs, female and male siblings and an unrelated female, had lameness attributed to osteochondritis dissecans (OCD) lesions noted at 6, 8, and 10 mo of age, respectively. All cubs were diagnosed with OCD via radiographs. The sibling cubs both had lesions of the right lateral femoral condyles, while the unrelated cub had bilateral lesions of the lateral femoral condyles. Subsequently, OCD was confirmed in all three cases during surgical correction of the lateral femoral condyle lesions via lateral stifle arthrotomies, flap removal, and debridement of the defect sites. Histopathology also supported the diagnosis of OCD. Postoperatively, the sibling cubs developed seromas at the incision sites and mild lameness, which resolved within a month. To date, two cubs have been orthopedically sound, while one of the sibling cubs has developed mild osteoarthritis. OCD has rarely been reported in domestic felids, and to the authors' knowledge these are the first reported cases of OCD in nondomestic felids. PMID- 22779241 TI - Hiatal hernia in a harbor seal (Phoca vitulina) pup. AB - A 2-wk-old stranded harbor seal (Phoca vitulina) rescued by Mystic Aquarium showed signs of the presence of a hiatal hernia during rehabilitation. Contrast radiographs of esophagus and stomach revealed an intrathoracic radiodensity that contains filling defects typical of stomach, consistent with gastric rugal folds. Mural thickening was observed at the level of the cardia consistent with a diagnosis of a hiatal hernia. Although clinical improvement was noted with medical therapy and tube feeding, surgical correction of the hiatal hernia was considered necessary for full resolution. However, owing to the animal's low body weight, the corrective hernia surgery was postponed until the body condition improved. The seal needed to be surgically treated for a corneal ulcer, and while anesthetized with isoflurane, the seal became dyspneic and developed cardiac arrhythmias; ultimately cardiac arrest ensued. Resuscitation was unsuccessfully attempted and the seal was euthanized. Necropsy confirmed the radiographic diagnosis and further characterized a paraesophageal hiatal hernia. PMID- 22779242 TI - Cardiac hemangioma in a corn snake (Pantherophis guttatus). AB - A 3-yr-old female corn snake, Pantherophis guttatus guttatus, was presented for clinical examination of anorexia and a coelomic mass. Radiographs and ultrasound demonstrated a fluid-filled mass in the cardiac region. Surgical exploration revealed an approximately 1.2-cm, round, multilobulated, fluid-filled, nodular lesion firmly attached to the left atrial wall. Resection was attempted but proved unsuccessful and the animal was euthanized. Histopathological examination of the lesion revealed a large cystic structure associated with a cluster of variably sized, vascular channels lined by a one-cell-thick layer of endothelium, consistent with a cardiac hemangioma of the left atrium. This, to the best of the authors' knowledge, is the first report of such an occurrence in a snake. PMID- 22779243 TI - Debilitation and mortality associated with besnoitiosis in four Virginia opossums (Didelphis virginiana). AB - Besnoitia spp. are coccidian parasites that infect a variety of wild and domestic mammals as well as some reptiles. Although infection with Besnoitia is common in Virginia opossums (Didelphis virginiana), clinical signs or death due to Besnoitia is rare. This manuscript describes four Virginia opossums that had severe clinical disease and inflammation associated with besnoitiosis. Clinical signs included trembling, incoordination, circling, blindness, poor body condition, and sudden death. Gross lesions included parasitic cysts in eyes, skin, and visceral organs. Histologically, cysts were often degenerate and associated with mild to marked inflammation, and amyloidosis was noted in one animal. Polymerase chain reaction and sequencing confirmed Besnoitia darlingi in three of the four opossums. PMID- 22779244 TI - Hemorrhagic and necrotizing hepatitis associated with administration of a modified live canine adenovirus-2 vaccine in a maned wolf (Chrysocyon brachyurus). AB - A 15-yr-old, female, maned wolf (Chrysocyon brachyurus) was euthanized after presenting semicomatose with severe, uncontrolled frank hemorrhage from her rectum 6 days following a routine physical examination and vaccination. Histopathology indicated severe hemorrhagic and necrotizing hepatitis with intranuclear basophilic inclusion bodies in the liver that were thought to be consistent with adenoviral infection. Further classification by polymerase chain reaction, immunohistochemical staining, virus isolation, and electron microscopy confirmed the etiologic agent to be canine adenovirus-2. A representative sample of the vaccine that had been used was submitted and sequenced along with the virus isolated from the maned wolf. The sequencing of the etiologic agent that had been isolated from the maned wolf was determined to be the same as the strain of virus used in the production of the modified live vaccine that had been administered 6 days prior to death. From this information, the diagnosis of vaccine-induced adenoviral hepatitis was made. This is the first confirmed case of vaccine-induced canine adenoviral hepatitis in a maned wolf. PMID- 22779245 TI - Serologic survey of brucellosis in captive neotropical wild carnivores in northeast Brazil. AB - Abstract. This study reports the detection of antibodies against Brucella abortus and B. canis in wild neotropical carnivores kept in captivity in three zoos in northeastern Brazil. A total of 42 serum samples were examined, 17 from coatis (Nasua nasua), eight from crab-eating raccoons (Procyon cancrivorus), three from crab-eating foxes (Cerdocyon thous), three from hoary foxes (Lycalopex vetulus), two from little spotted cats (Leopardus tigrinus), five from tayras (Eira barbara), two from greater grisons (Galictis vittata), and two from neotropical river otters (Lontra longicaudis). The Rose-Bengal test and complement fixation test (CFT) were performed to detect anti-Brucella spp. antibodies, whereas the agar gel immunodiffusion test (AGID) was employed to detect anti-B. canis antibodies. The overall seroprevalence varied by species and by test; in addition, CFT and AGID seemed better able to detect antibodies against B. abortus and B. canis, respectively. This is the first study on the presence of anti Brucella spp. antibodies in captive carnivores from Brazil, as well as the first report of antibodies to Brucella spp. in coatis, crab-eating raccoons, hoary foxes, little spotted cats, tayras, and greater grisons. PMID- 22779246 TI - Outbreak of type C botulism in captive wild birds. AB - In late summer 2010, an outbreak of type C botulism affected the birds kept in a dam at a southern Brazilian zoo. A total of 14(10 black-necked swans, Cygnus melancoryphus; 3 Muscovy ducks, Cairina moschata; and 1 fulvous whistling-duck, Dendrocygna bicolor) out of 100 birds died after showing flaccid paralysis of the skeletal muscles characterized by general locomotion deficit, flight and swimming disorders, dropped neck, and severe dyspnea. Carcasses of dead birds (some infested by larvae of sarcophagus fly) scattered in the bird enclosure, and oxygen-free, organically rich mud and/or shallow standing waters present at the edges of the weir were identified as possible toxin sources. Postmortem examinations revealed no significant pathological changes. Epidemiologic and clinical findings indicated the diagnosis of type C botulism toxin, which was confirmed by mouse bioassay and seroneutralization. PMID- 22779247 TI - Mycobacterium avium subspecies paratuberculosis cultured from the feces of a Southern black rhinoceros (Diceros bicornis minor) with diarrhea and weight loss. AB - Abstract: Mycobacterium avium paratuberculosis (Map) was cultured from the feces of a wild-caught, female, adult Southern black rhinoceros. The animal, which presented with a 4-mo history of diarrhea and weight loss, was prescribed a course of antimycobacterial drugs. The clinical signs resolved, and the feces were repeatedly culture negative thereafter. Although the Rhinocerotidae are likely to be resistant to Johne's disease, this case raises the possibility that they can become transiently infected with the causative organism. PMID- 22779248 TI - Hemorrhagic enterocolitis and death in two felines (Panthera tigris altaica and Panthera leo) associated with Clostridium perfringens type A. AB - Severe hemorrhagic enterocolitis was observed in a Siberian tiger (Panthera tigris altaica) and a lion (Panthera leo). Both animals developed acute depression, anorexia, and bloody diarrhea several days before death. Small and large intestines were diffusely congested, edematous, necrotic, and filled with hemorrhagic fluid, and mesenteric lymph nodes were enlarged and congested. Pure and abundant growth of gram-positive bacilli was obtained in culture under anaerobic conditions from the livers of both felines. Identification of highly virulent Clostridium perfringens Type A was based on pathologic lesions, hemolytic patterns, morphologic structure, and polymerase chain reaction. Animal inoculation assays indicated that C. perfringens Type A played an important role in the pathogenesis of both felines. PMID- 22779249 TI - Magnetic resonance imaging diagnosis of intervertebral disc disease and myelomalacia in an American black bear (Ursus americanus). AB - A 23-yr-old black bear (Ursus americanus) was examined because of paralysis of unknown duration. The precise onset of clinical signs was unknown as a result of seasonal torpor. The bear was immobilized and transported to a university veterinary teaching hospital for further evaluation and treatment. Radiography revealed increased mineral opacity and ventral bridging across vertebral segments T8-11. Magnetic resonance imaging demonstrated dorsal and ventral compression of the spinal cord at T8-9. Given the bear's advanced age, the unknown duration of spinal cord compression, unknown presence of deep pain perception, and thus an unknown prognosis for surgical success, euthanasia was elected. Postmortem examination revealed severe spondylosis deformans from T7 to L3 and dorsal extradural extruded disc material in the area of T8-9. Histopathology demonstrated the dorsal horns of the spinal cord at T9 were replaced by foamy macrophages extending into the dorsal and lateral funiculi of the white matter compatible with focal, severe, chronic myelomalacia. This is the first report of intervertebral disc disease and myelomalacia diagnosed using MRI in a large carnivore. PMID- 22779250 TI - Surgical removal of an abscess associated with Fusarium solani from a Kemp's ridley sea turtle (Lepidochelys kempii). AB - A cold-stunned Kemp's ridley sea turtle, Lepidochelys kempii, developed an abscess associated with Fusarium solani, Vibrio alginolyticus, and a Shewenalla species after receiving a bite wound to the front flipper during rehabilitation. The lesion failed to respond to medical therapy and was treated successfully with surgery. Histopathology of the excised tissue demonstrated septic heterophilic inflammation with necrosis and granulation tissue, fungal elements, and bacteria, despite appropriate antimicrobial therapy. Variably thick bands of dense collagenous tissue partially surrounded affected areas which might have limited drug penetration into the tissue. Postoperative healing and eventual releases were uneventful. This is the first report of surgical treatment of cutaneous Fusarium infection in a sea turtle and supports surgery as an effective treatment for a fungal abscess in a reptile. PMID- 22779251 TI - Disseminated pheochromocytoma in a North American river otter (Lontra canadensis). AB - A 21-yr-old male North American river otter (Lontra canadensis) with a chronic history of degenerative osteoarthritis was evaluated for acute posterior paralysis. Because no definitive cause was identified and a poor prognosis was expected, the otter was euthanatized. A malignant neoplasm of adrenal gland origin with disseminated metastases to the central nervous system, lymph nodes, diaphragm, pancreas, spleen, and liver was diagnosed on postmortem examination. No clinical signs of disseminated neoplasia had been noted throughout the otter's history. The adrenal neoplasm was composed of nests of epithelial cells surrounded by a fine fibrovascular stroma. Neoplastic cells were immunohistochemically positive for chromogranin A, PGP9.5, metencephalin, and endorphin and negative for melan A and inhibin, confirming a diagnosis of a malignant pheochromocytoma. On the basis of the necropsy finding, metastasis of the pheochromocytoma might have contributed to the observed clinical signs. PMID- 22779252 TI - Anisakiasis with proventricular perforation in a greater shearwater (Puffinus gravis) off the coast of Georgia, United States. AB - A juvenile male greater shearwater (Puffinus gravis) found off the Georgia coast, United States, was lethargic, hypothermic, dehydrated, and emaciated. It was provided with supportive care but subsequently died. The coelomic cavity contained fibrinous fluid intermixed with hundreds of nematodes, some of which protruded through a perforation in the proventriculus. Nematodes were embedded in the wall of the proventriculus from the lamina propria to the serosal surface and were surrounded by granulocytes, epithelioid macrophages, multinucleate giant cells, lymphocytes, and fibroplasia. A full-thickness tear in the proventriculus was lined by heterophils and multinucleate giant cells. The nematode histomorphology was consistent with Anisakis spp. The definitive hosts of Anisakis spp. are marine mammals, which are infected through ingestion of parasitized fish and crustaceans. Marine birds are aberrant hosts of Anisakis spp., and young, inexperienced, immunocompromised birds might be more susceptible to severe infestations. Fatal anisakiasis is rarely reported in birds. PMID- 22779253 TI - Typhlitis and abdominal cystic lymphangiomatosis in a Mt. Carmel blind mole rat (Nannospalax (ehrenbergi) carmeli). AB - An abdominal cystic lymphangiomatosis in a Mt. Carmel blind mole rat (Nannospalax (ehrenbergi) carmeli) is described. This case was most likely due to a congenital abnormality with long-term compensation by the animal. The case describes the clinical course and subsequent postmortem examination. The death in the animal was caused by an abscess in the peritoneal wall and subsequent peritonitis. PMID- 22779254 TI - Lethal Procyrnea infection in a black-backed woodpecker (Picoides arcticus) from California. AB - The black-backed woodpecker (Picoides arcticus) is a species of management concern in California. As part of a study of black-backed woodpecker home range size and foraging ecology, nine birds in Lassen National Forest (Shasta and Lassen Counties, California) were radio-tracked during the 2011 breeding season. One of the marked birds was found dead after being tracked for a 10-wk period in which it successfully nested. A postmortem examination of the dead bird revealed that it was emaciated and autolyzed, with the presumptive cause being numerous spiruroid nematodes of the genus Procyrnea in the gizzard. This first observation of Procyrnea nematodes in a black-backed woodpecker is notable because the Procyrnea infection was considered lethal and because Procyrnea has been implicated in substantial die-offs in other bird species, including woodpeckers. PMID- 22779255 TI - Conservative management of pyothorax in an Amur tiger (Panthera tigris altaica). AB - Therapy for pyothorax, or pleural empyema, has not been described for large felids. This case describes the successful treatment of pyothorax in a captive, large felid. A 15-yr-old multiparous, female Amur tiger (Panthera tigris altaica) presented with nonspecific clinical signs caused by an insidious onset of pyothorax. Management of pyothorax cases in companion animals often involves thoracostomy tube placement with recurrent drainage of the pleural cavity, intensive supportive care, and monitoring. In this case, conservative management was elected because hospitalization was not a viable option. Thoracocentesis was performed to drain as much fluid from the chest cavity as possible, yielding more than 1.3 L. Corynebacterium sp. and unidentified anaerobic gram-positive cocci were cultured. Treatment included cefovecin subcutaneously, oral antibiotic therapy with clindamycin and marbofloxacin, meloxicam, and restricted exercise by minimizing access to the main exhibit. Significant improvement was noted clinically and radiographically 6 wk later, and no relapses were noted in the following weeks. An examination 11.5 mo later confirmed resolution. PMID- 22779256 TI - Hepatic capillariasis in captive ring-tailed lemurs (Lemur catta). AB - A female ring-tailed lemur (Lemur catta) and her two cubs held in a zoo in Chile exhibited signs of severe hepatic insufficiency. In spite of supportive treatment, the three animals died a few days after the onset of signs. Postmortem examination revealed ascites and fibrotic lesions in the liver of all the individuals. Histologically, the liver of two of them showed a severe parasitic ova infection and lipidosis, the morphologic characteristics of the parasitic ovas were consistent with Capillaria hepatica (syn. Calodium hepatica) eggs. To the authors' knowledge, this is the first clinical case report of hepatic capillariasis in prosimians, and its implications are discussed. PMID- 22779257 TI - To the moons, NASA: Planetary science is NASA's most successful and inspirational program. It should not be gutted. PMID- 22779258 TI - How to fulfill the true promise of "mHealth": Mobile devices have the potential to become powerful medical tools. PMID- 22779259 TI - A home on the range: After years of legal wrangling, the U.S. government says it will designate critical habitat for the jaguar. PMID- 22779260 TI - Trashing the "element from hell': experts say we should bury leftover plutonium. PMID- 22779261 TI - Why sneezing is good for you: Allergies may have emerged to protect us from environmental toxins. PMID- 22779262 TI - Who's #1? Why rankings are flawed. PMID- 22779263 TI - Bad for bugs and brains? A common pesticide may interfere with a child's brain development. PMID- 22779264 TI - The last worm: a dreaded tropical disease is on the verge of eradication. PMID- 22779265 TI - How critical thinkers lose their faith in God: faith and intuition are intimately related. PMID- 22779266 TI - Tracking turtles from space: a satellite study pinpoints where leatherbacks and fishing trawlers cross paths. PMID- 22779267 TI - Perils of newborn screening: doctors may be testing infants for too many diseases. PMID- 22779268 TI - Technology that doesn't fly: outdated screening rules aren't making for safer skies--just longer lines. PMID- 22779269 TI - Why we help: Far from being a nagging exception to the rule of evolution, cooperation has been one of its primary architects. PMID- 22779270 TI - Reading the Red Planet: at 10:31 p.m. Pacific time on August 5, NASA's Curiosity rover will begin the first direct search for habitable environments on Mars. PMID- 22779271 TI - Secrets of the HIV controllers: A rare group of HIV-positive individuals need no medicine to keep the virus in check. Their good fortune could point the way to more powerful treatments--and perhaps a vaccine. PMID- 22779272 TI - Fleet of foot: Nimble robots like this "Cheetah" will help the military navigate terrain too rocky for wheels. PMID- 22779273 TI - Witness to an Antartic meltdown: As glaciers collapse toward the sea, scientists struggle to figure out how fast the southern continent is melting and what that means for sea-level rise. PMID- 22779274 TI - Nobel pursuits: The tools of science have changed since the golden age of physics, but many of the same questions remain. PMID- 22779275 TI - The rat that laughed: Do animals other than humans have a sense of humor? Maybe so. PMID- 22779276 TI - Machines that think for themselves: new techniques for teaching computers how to learn are beating the experts. PMID- 22779277 TI - Aunt Millie's mind: The death of the brain means subjective experiences are neurochemistry. PMID- 22779278 TI - Influence of CAD/CAM systems and cement selection on marginal discrepancy of zirconia-based ceramic crowns. AB - PURPOSE: To analyze the effect of ceramic manufacturing technique and luting cement selection on the marginal adaptation of zirconium oxide-based all-ceramic crowns. METHODS: An extracted mandibular first premolar was prepared for a complete coverage restoration and subsequently duplicated 40 times in a liquid crystal polymer (LCP). All-ceramic crowns (n = 10) were fabricated on LCP models using the following systems: glass-infiltrated zirconia-toughened alumina (In Ceram Zirconia) and yttrium cation-doped tetragonal zirconia polycrystals (In Ceram YZ, Cercon, and Procera Zirconia). The restorations (n = 5) were cemented on their respective dies with glass-ionomer cement (Ketac Cem Aplicap) and resin cement (Panavia 21). The absolute marginal discrepancy of the crowns was measured before and after cementation by scanning electronic microscopy at 160 points along the circumferential margin. The data were analyzed using one-way ANOVA for repeated measures and for independent samples, Scheffe's multiple range post hoc test, and Student's t-test (alpha = 0.05). RESULTS: There were statistical differences in the mean marginal openings among the four all-ceramic systems before and after luting (P < 0.0001). The Procera restorations had the lowest pre and post-cementation values (P < 0.0001). A significant increase in the marginal gap size caused by luting media occurred in all tested groups (P < 0.0001). Resin cement resulted in larger marginal discrepancies than glass-ionomer cement (P < 0.0001). PMID- 22779279 TI - Influence of surface pretreatment on the short-term bond strength of resin composite to a zirconia-based material. AB - PURPOSE: To evaluate the influence of airborne-particle abrasion of zirconia before and after sintering, on the bond strength between a zirconia core and an indirect resin composite material. METHODS: 9 disks of Y-TZP zirconia core were prepared and divided into three equal groups. In Group 1 pre-sintered Y-TZP zirconia was airborne-particle abraded with 120 microm alumina oxide. In Group 2 sintered Y-TZP zirconia was airborne-particle abraded with 120 microm alumina oxide. In Group 3 sintered Y-TZP zirconia was not treated and thus served as the control group. A 10-methacryloylooxydecyldihydrogenphosphate (MDP) containing bonding agent and silane coupling agent mixture was applied to the disks in all three experimental groups. Resin composite for indirect restorations was incrementally layered in a plastic mold to a final thickness of 3 mm. Specimens were sectioned under water cooling to obtain microsticks 6 x 1 x 1 mm in dimension. 30 microsticks per experimental group were generated. Microtensile bond strength test was conducted with a universal testing machine. Fractured microsticks and sections from each group were also examined under an optical microscope and a scanning electron microscope to evaluate respectively the mode of failure and the zirconia-composite interface. T-test for independent samples was selected to analyze the data. The level of significance was set at P < 0.05. RESULTS: Airborne-particle abraded groups resulted in mean (SD) bond strength values of 25.65 (7.23) MPa for Group 1 and 24.65 (12.33) MPa for Group 2. Bond failures were mainly interfacial. In the control group a high number of premature failures occurred during cutting process and the mean (SD) bond strength recorded was 3.36 (4.17) MPa. It was concluded that airborne-particle abrasion of a zirconia substrate combined with application of a MDP-containing bonding/silane coupling agent mixture resulted in an adequate resin composite bond. Airborne particle abrasion performed before sintering zirconia did not produce any significant differences. PMID- 22779280 TI - Effect of the length of glass fiber posts on the fracture resistance of restored maxillary central incisors. AB - PURPOSE: To evaluate the influence of post length insertion on the fracture resistance of directly restored endodontically treated teeth. METHODS: 30 maxillary central incisors were restored with glass fiber posts and composite cores to produce groups with post lengths of (1) 5 mm, (2) 7 mm, and (3) 9 m. Specimens were loaded at 130 degrees (Instron). Fracture strengths were analyzed with the Kolmogorov-Smirnov Test to verify the normality of the data distribution and with ANOVA and Tukey's post hoc test at P < 0.05. Fracture patterns (restorable or unrestorable) were analyzed (Pearson's Chi-square test). RESULTS: The average fracture resistance was: Group 1 = 366.4 N, Group 2 = 507.4 N and Group 3 = 509.9 N. No significant difference was found among the three groups for fracture resistance or for failure mode. The insertion length did not influence the fracture pattern; more restorable fractures were detected. PMID- 22779281 TI - Brush head wear, subject-perceived and laboratory cleaning performance of two oscillating-rotating electric toothbrush heads over 3 months. AB - PURPOSE: To evaluate the progression of wear and the effect of wear on subject perceived and laboratory cleaning efficacy of two oscillating-rotating electric brush heads, Oral-B Precision Clean (PC) and a store brand Easyflex (SB) brush head, after 4, 6, 8 and 13 weeks of use. METHODS: This research consisted of three phases: (1) Subject questionnaires--A crossover, single-blinded study was conducted among healthy adults who were regular users of Oral-B oscillating rotating electric toothbrushes. Subjects were recruited from a general population and randomized based on age and gender into one of four cohorts reflecting the time period of use for each product: 4, 6, 8 or 13 weeks. After brushing with their first product (either PC or SB) for the designated period of time, subjects completed a questionnaire evaluating the brush head on 17 attributes related to perceived cleaning performance, brush head condition (i.e., durability) and brush head feel (i.e., gentleness). Subjects then used the second test product for the same period of time and completed the same questionnaire. (2) Wear index investigation--At the end of each time period, subjects' worn brush head pairs were evaluated by an independent, blinded investigator to determine the wear index score. (3) Robot testing--To analyze the laboratory cleaning efficacy of worn refills in the laboratory, a representative sample of 12 subject brush head pairs for each of the four cohorts were evaluated (96 brush heads in total). To analyze the laboratory cleaning efficacy for PC at Week 13 with SB at Week 4, a separate set of 20 subjects (40 brush heads in total) were evaluated. A robot was used to brush standard typodonts (Frasaco A3) covered with plaque substitute with the worn brush head for 2 minutes under standardized, controlled conditions simulating human brushing behavior. A 3D laser scan system was used to measure the area still covered with plaque substitute at different dental sites. RESULTS: Subject questionnaire--267 subjects completed study questionnaires. Statistically significant superior ratings (P < 0.05) were obtained with the PC brush head compared to the SB brush head for virtually all attributes at all four time periods (16/17 attributes for Weeks 4, 6 and 8 and 17/17 at Week 13). Highly significant advantages (P < 0.0001) were seen for 'overall rating', 'overall cleaning' and 'ready to replace brush head' attributes. Wear Index-- A total of 486 brush head samples (243 pairs) were analyzed for wear. At all four time periods, PC brush heads had a statistically significantly lower (P < 0.0005) mean wear index than SB brush heads. Robot Test--136 brush heads were analyzed using a laboratory (robot) test to investigate cleaning efficacy. Directionally higher laboratory cleaning for PC versus SB was observed for all dental sites (35/35) for all time periods. Comparing PC at Week 13 with SB at Week 4 showed statistically significant differences (P < 0.05) in favor of PC for the majority of dental sites and time periods (23/35). PMID- 22779282 TI - Influence of in-office whitening gel pH on hydrogen peroxide diffusion through enamel and color changes in bovine teeth. AB - PURPOSE: To assess the influence of in-office whitening gel pH on whitening efficiency. METHODS: Hydrogen peroxide diffusion and color changes on bovine teeth were assessed. Three gels with close hydrogen peroxide concentrations but with various pH levels were tested: Zoom 2 (Discus Dental), Opalescence Endo and Opalescence Boost (Ultradent). The pH levels were respectively: 3.0, 5.0 and 7.0. Thirty enamel slices and tooth crowns were used for both studies (n = 10 per group per study). Hydrogen peroxide diffusion through the enamel slices and the tooth crowns was spectrophotometrically recorded every 10 minutes for 1 hour to calculate the diffusion coefficients. Color changes were spectrophotometrically recorded every 10 minutes for 1 hour and quantified in term of CIE-Lab. RESULTS: The hydrogen peroxide diffusion coefficient through enamel ranged from 5.12 +/- 0.82 x 10(-9) cm2 s(-1) for pH 3 to 5.19 +/- 0.92 x 10(-9) cm2 S(-1) for pH 7. Through tooth crowns it ranged from 4.80 +/- 1.75 x 10(-10) cm2 s(-1) for pH 5 to 4.85 +/- 1.82 x 10(-10) cm2 s(-1) for pH 3. After 1 hour, the deltaE varied from 5.6 +/- 4.0 for pH 7 to 7.0 +/- 5.0 for pH 3 on enamel slices and from 3.9 +/- 2.5 for pH 5 to 4.9 +/- 3.5 for pH 7 on tooth crowns. There was no statistically significant difference between groups for both parameters. PMID- 22779283 TI - Influence of shade and light-curing distance on the degree of conversion and flexural strength of a dual-cure core build-up resin composite. AB - PURPOSE: To investigate the influence of shade and light-curing distance on the degree of conversion (DC) and flexural strength (FS) of a dual-cure core build-up resin composite. METHODS: 135 specimens were prepared and divided into three main groups according to the shade of the composite core material; dentin, blue and white shades. Each group was further subdivided into three subgroups according to the light-curing distance; 0 mm, 3 mm and 5 mm. The DC was measured using FTIR spectrometer. For testing the FS, the mini flexural test specimens were prepared and subjected to three point bending test in a universal testing machine. The results were analyzed using two-way and one-way ANOVA followed by Duncan's Multiple Range Test. The significance level was set at P = 0.05. RESULTS: Both the DC and FS of the dual-cure core build-up material used in this study were influenced by the shade of the material and the light-curing distance. The blue shade exhibited the highest percentage DC values while the white shade revealed the lowest percentage DC. The dentin shade at 0 mm light-curing distance exhibited the highest mean FS value; however the 3 mm and 5 mm light-curing distance of the white shade showed the lowest mean FS values. PMID- 22779284 TI - Bonding of primed zirconia ceramics: evidence of chemical bonding and improved bond strengths. AB - PURPOSE: To investigate changes of zirconia surface hydrophobicity (contact angle) following the application of a zirconia primer as a function of post priming storage period and after exposure to harsh conditions and to analyze whether there is a chemical bond formation between a zirconia primer and zirconia ceramics. METHODS: Zirconia ceramics were treated with a zirconia primer (ZPrime Plus, Bisco), left undisturbed for specific times (reaction time), followed by ultrasonic cleansing in ethanol or acetone bath, and then contact angles were measured (n = 10). The primed zirconia ceramics were also subjected to harsh conditions (strong acid or boiling water) prior to contact angle testing. The chemical change of zirconia surface with and without being primed was analyzed by time-of-flight secondary ion mass spectroscopy (TOF-SIMS). Shear bond strength (Ultradent jig method) on zirconia surface was tested using different zirconia primers. The data were statistically analyzed using one-way ANOVA and Tukey's post-hoc test with 95% confidence level. RESULTS: The contact angle on the primed zirconia surface (from 56 degrees to 72 degrees for different primers) was significantly higher than that of unprimed zirconia (15 degrees) (P < 0.05). Contact angles were maximized as the reaction time increased within 5 minutes (increased from 58 degree at 10 seconds, to 72 degrees at 5 minutes). Exposure to harsh conditions (i.e. strong acid or boiling water) exhibited no significant change in contact angle values (P > 0.05). The TOF-SIMS detected fragmentations with mass of 549 and 411, indicating that a chemical group of phosphate monomer(P)-O-Zr existed, which indicated a chemical bond was formed between zirconia and ZPrime Plus. All of the zirconia primers tested in the study significantly improved zirconia bond strengths (4 MPa for unprimed zirconia, and 17-23 MPa for primed zirconia, P < 0.05). PMID- 22779285 TI - Microhardness recovery of demineralized enamel after treatment with fluoride gel or CPP-ACP paste applied topically or with dielectrophoresis. AB - PURPOSE: To evaluate the microhardness of demineralized enamel remineralized in saliva after applying 1.23% APF gel or CCP-ACP paste with dielectrophoresis (DEP) or diffusion for 3 minutes. METHODS: In this laboratory study, 25 enamel blocks of bovine incisors were soaked in demineralizing solution (10 mM HCl pH 2.5) for 10 minutes and remineralized in saliva for 1 hour, after applying 1.23% APF gel or CPP-ACP paste without fluoride with dielectrophoresis or conventional topical application for 3 minutes. The mean and percentage changes of surface microhardness in pre-demineralization, post-demineralization and remineralization stages were measured in the five groups. The results of all five groups during the three stages were compared by ANOVA and paired t-tests (P = 0.05). RESULTS: The average surface microhardness recovery of APF gel (12,300 ppm fluoride) applied with DEP was higher than APF gel applied topically, or CPP-ACP paste applied with DEP or topically, and water control (P < 0.05). The percentage of surface microhardness recovery for APF+DEP, APF+Diffusion, CPP-ACP+DEP, CPP ACP+Diffusion, and water control were 88.17%, 13.62%, 7.14%, 5.45%, and 4.02%, respectively. Demineralization treatment decreased the surface microhardness of enamel in all groups and the surface microhardness recovery in the APF+DEP group was significant (P < 0.001). The only significant paired difference was between APF+DEP and all other groups. No other paired difference approached significance. Surface microhardness recovery of enamel with APF+DEP was 12 times or 1,200% greater than APF gel applied topically, and CPP-ACP paste either applied topically or with DEP in one 3-minute application. PMID- 22779286 TI - Fluoride plus CO2 laser against the progression of caries in root dentin. AB - PURPOSE: To evaluate the effect of a 1.23% acidulated phosphate fluoride (APF) gel combined with CO2 laser in protecting carious root dentin against further cariogenic challenges. METHODS: After a 7-day lead-in period, 12 volunteers wore an intraoral palatal device containing four carious root dentin slabs, treated with APF and APF+CO2 or placebo and placebo+CO2. After a 14-day wash-out period, volunteers were crossed-over to the other treatment arm. During both intraoral phases, specimens were submitted to cariogenic challenges and then evaluated for cross-sectional Knoop microhardness. RESULTS: Two-way ANOVA demonstrated that there was significant effect for both main factors: CO2 laser irradiation (P < 0.0001) and gel treatment (P < 0.0001), and that there was no interaction between them (P = 0.4706). Protection of carious root dentin against further cariogenic challenges may be provided by APF fluoride gel and CO2 laser, but no additive benefit was found by combining such strategies. PMID- 22779287 TI - Assessment of chewing sugar-free gums for oral debris reduction: a randomized controlled crossover clinical trial. AB - PURPOSE: To assess the oral debris removal efficacy of two commercial sugar-free chewing gums, based on a newly developed oral debris scoring system. METHODS: A randomized, examiner-blinded, three-arm crossover study was conducted, with a 1 week washout period between the crossover phases. 42 healthy adults were randomly assigned to sugar-free stick gum (Wrigley's Extra Freshmint), sugar-free pellet gum (Wrigley's Extra Fruit) or no-gum chewing groups. Subjects consumed a single chocolate cookie, and were examined at baseline, and at 2-, 5-, and 10-minute time points with or without gum-chewing treatment. Primary outcome measures were oral debris scores on the occlusal surface, interproximal and gingival margin areas. The entire test procedure was repeated on two subsequent visits. RESULTS: The baseline conditions in the three groups did not differ significantly. Chewing either stick gum or pellet gum resulted in significantly lower oral debris scores (P < 0.0001) compared to the control (no-gum) treatment for all intraoral sites, while no significant difference was observed between the two chewing gum groups. Intra-examiner repeatability of the new scoring criteria was high throughout the study (Kappa > 0.90). PMID- 22779288 TI - Masking of temperature-induced color changes in a thermo-sensitive fiber post. AB - PURPOSES: To evaluate (1) the efficacy of the color changing technology featured by DT Light Illusion Post aimed at safely identifying the post in case of re treatment, and (2) the efficacy of a resin composite layer to mask the post if color shift occurs due to cold food and beverages. METHODS: Five "master disks" of 3 mm of thickness were prepared by embedding in a resin composite four thermo sensitive posts and one translucent post (control) cut in bars. Disks of resin composite in 0.5/1.0/1.5 mm thickness were prepared as well. Digital images were taken of the master disks with and without the overlying of the resin composite disks, at 5 degrees C and at 35 degrees C temperature. By the use of Adobe Photoshop "layering function" and "multi-layer option", differences in color were calculated between the post-free and the post-containing areas. RESULTS: The differences between the resin color and post color were remarkably higher when the temperature was 5 degrees C, showing that the technology of color change of the post was effective. With resin disk overlaid, at 35 degrees C none of the differences in color were above the threshold for clinical acceptability. At 5 degrees C blue and black colored posts were visible when the overlaid resin thickness was 0.5 mm, while at 1.0 mm and 1.5 mm none of the posts were visible. PMID- 22779289 TI - Plagiarism or "copy-paste" manipulation. PMID- 22779290 TI - Self-assessment of the quality of life of children and adolescents in the child welfare system of Serbia. AB - BACKGROUND/AIM: Children and adolescents who enter a child welfare system are at higher risk of suffering from mental disorders, physical health, and/or social and educational problems than the general population of the same age is. This study was organized with the aim to evaluate the general characteristics of quality of life (QOL) in children and adolescents living in residential and foster care in Serbia. METHODS: Two hundred and sixteen children and adolescents, aged 8-18 years, from residential and foster care and 238 children and adolescents from the general population participated in the study. QOL was assessed using the Pediatric Quality of Life Inventory (PedsQL) - Serbian version. Three groups were created: residential care group (RCG), foster care group (FCG), and control group (children and adolescents from biological families - CG). Descriptive data were calculated for all questionnaires' scores, while t test and ANOVA were used to compare them. RESULTS: The mean value of the total PedsQL was lower in the RCG, 67.47 +/- 17.75, than in the FCG and the CG, 88.33 +/- 11.27 and 80.74 +/- 11.23, respectively. Additionally, the RCG reported lower all PedsQL Scale scores, but the lowest value was for the psychosocial domain. These differences were statistically significant (F value ranged from 17.3 to 49.89, p < 0.000). However, only the scores of the RCG were statistically different from the FCG and the CG, while the differences between the FCG and the CG were statistically insignificant (p > 0.05). CONCLUSION: Children and adolescents living in residential care have significantly poorer QOL than those living in foster care or in biological families. On the other side, QOL in children and adolescents from foster care is similar to the one of those living in biological families. PMID- 22779291 TI - [Premortal data in the process of skeletal remains identification]. AB - BACKGROUND/AIM: The basic task of a forensic examiner during the exhumation of mass graves or in mass accidents is to establish identity of a person. The results obtained through these procedures depend on the level of perceptibility of post mortal changes and they are compared with premortal data obtained from family members of those missing or killed. Experience with exhumations has shown significant differences between the results obtained through exhumation and the premortal data. The aim of the study was to suggest the existance of the difference between premortal data and the results obtained by exhumation regarding the some parameters, as well as to direct premortal data colection to the specific skeletal forms. METHODS: We performed comparative analysis of the results of exhumation of skeletal remains in a mass grave and the premortal data concerning the identified persons. The least number of individuals in this mass grave was calculated according to the upper parts of the right femur and it helped in calculating the smallest number of individuals in mass graves to be 48. A total of 27 persons were identified. Sex was determined by metrics and morphology of the pelvis. Personal age in the moment of death was determined by morphology features of groin symphisis and morphology of sternal edge of ribs and other parts of scelets observations. The hight was calculated as average results of length of long bones and Rollet coefficients. RESULTS: There was a complete match in terms of sex and age matched within an interval that could be established based on the skeletal remains. All the other parameters were different, however, which made identification significantly more difficult. CONCLUSION: The premortal data is an important element of identification process and it should be obtained by the forensic doctor and directed towards more detailed examination of the skeletal system. PMID- 22779292 TI - Influence of NG-nitro-L-arginine methyl ester on clinical and biochemical effects of methylene blue in pentylenetetrazole-evoked convulsions. AB - BACKGROUND/AIM: Despite years of research in a number of experimental models the question whether nitric oxide (NO) and methylene blue (MB) have pro- or anticonvulsant effects remains to be fully resolved. Methods. In adult Wistar rats the influence of a nonselective inhibitor of nitric oxide synthase NG-nitro L-arginine methyl ester (L-NAME, 10 microg) on clinical and biochemical effects of MB (10 microg) given before the intraperitoneally administered chemical convulsant pentylenetetrazole (PTZ, 80 mg/kg) was examined. MB and L-NAME were applied intracerebroventricularly. PTZ application was followed by a 4-minute observation time, after which rats were sacrificed and elements of oxido reductive balance were measured in a crude mitochondrial fraction of forebrain cortex, hippocampus and striatum. RESULTS: Convulsive responses (forelimb dystonia--FLD, generalised clonic- and clonic-tonic convulsions--GCC and GCTC respectively) were observed in all rats received PTZ, together with significantly decreased lipid peroxidation in the forebrain cortex and striatum and increased superoxide dismutase activity in the hippocampus, in comparison to controls (saline treated). It was registered anticonvulsant effects of L-NAME pretreatment. However, these effects were insignificant. In the hippocampus of these animals there was decreased lipid peroxidation (p < 0.01, p < 0.05 vs saline-treated and PTZ-treated rats, respectively) and reverted PTZ-induced increase of superoxide dismutase activity. But MB individually pretreatment significantly decreased the incidence of CTCs and GCCs (FLD: p = 0.0513), prolonged the convulsive latent time for FLD, GCTCs and GCCs, in all the examined brain regions increased lipid peroxidation and decreased the level of superoxide anion. Administration of L-NAME 10 minutes before MB reverted all MB-evoked clinical and biochemical effects. CONCLUSION: Methylene blue applied individually before PTZ has strong anticonvulsant effects that were eliminated by L-NAME pretreatment. These effects and changed biochemical parameters in the brains of animals treated by L-NAME before MB in comparison to MB-treated group suggest involvement of NO in MB's effects in the animal model of PTZ-evoked convulsions. PMID- 22779293 TI - Tongue mobility in patients with cerebral palsy. AB - BACKGROUND/AIM: In children with cerebral palsy speech is a big problem. Speech of these children is more or less understandable, depending on the degree of reduced mobility of articulatory organs. Reduced mobility is affected by inability to control facial grimacing and poor muscle strength when performing targeted movements. The aim of this study was to determine the mobility of tongue in patients with cerebral palsy. METHODS: The study included a sample of 34 children--patients with cerebral palsy who had been treated in the Special Hospital for the Cerebral Palsy and Developmental Neurology in Belgrade. The patients were divided according to the determined diagnosis into two groups: Quadriparesis spastica (n = 11) and Morbus Little (n = 16). The children, aged 8 12 years, had preserved intelectual abilities, and all of them had preserved hearing. The study was conducted during the period from January to September 2009. The functional state of articulatory organs in both groups was tested by the C-test that examines the anatomic structure and mobility of the articulatory organs. RESULTS: Our research showed that both groups of the patients had impaired functional state of the tongue - the most mobile articulatory organ. Also, the research showed that the functional state of the tongue was worse in children diagnosed with Quadriparesis spastica. A statistically significant correlation between the diagnosis and the functional state of the tongue, the tongue test performance and the retention of the tongue in a given position was found (r = 0.594, p < 0.005; r = 0.816, p < 0.01 and r = 0.738, p < 0.001, respectively). CONCLUSION: A large percentage of children with cerebral palsy were not able to establish control over the position of articulatory organs, especially the tongue, and its retention in a given position, all of which affect the quality of speech. PMID- 22779294 TI - The prognostic value of amplitude-integrated electroencephalography in neonates with hypoxic-ischemic encephalopathy. AB - BACKGROUND/AIM: Diagnosis of perinatal hypoxic-ischemic encephalopathy (HIE) and early prediction neurological outcome is important and difficult. The aim of this study was to determine the prognostic value of amplitude-integrated electroencephalography (aEEG) for abnormal neurodevelopment outcome in a neonate with HIE. METHODS: A total of 90 neonates > 32 gestational age (GA) with HIE were enrolled prospectively. All neonates with HIE were categorized into three grades according to the Sarnat and Sarnat clinical scoring system (mild HIE, moderate HIE and severe HIE). aEEG traces were recorded with a cerebral function monitor (CFM) during the first 72 h of life. The neurodevelopment outcome was assessed at 12 months of age of corrected gestational age. RESULTS: The pattern of aEEG correlated with the severity of HIE (p < 0.0001) and subsequent neurodevelopment outcome (p < 0.001). We found that aEEG background patterns exhibited superior prediction of abnormal outcomes at 12 months of age (sensitivity of 91.7% and specificity of 94.3%, positive predictive value of 78.6% and negative predictive value of 98.1%) when compared to aEEG seizure (sensitivity of 94% and specificity of 48%, positive predictive value of 57% and a negative predictive value of 92%). Electroclinical dissociation seizure was detected in 28% of the neonates with HIE. CONCLUSIONS: Our results confirm that aEEG is simple and accurate bedside diagnostic method for assessing extension of hypoxic-ischemic brain damage and early identification of neonates with perinatal HIE who are at high risk of neurodevelopmental impairment. PMID- 22779295 TI - Intensity of hemorrhage following tonsillectomy. AB - BACKGROUND/AIM: Although post-tonsillectomy hemorrhage is one of the most frequent and potentially life-threatening complications, there is no generally accepted classification of post-operative bleeding intensity. The aim of this study was to evaluate the intensity of post-tonsillectomy hemorrhage according to the five-grade classification. METHODS: A total of 408 consecutive patients, aged 2 to 54 years, undergoing elective tonsillectomy, with (n = 261) or without (n = 147) adenoidectomy, were included in this prospective study. Tonsillectomy was performed under general anesthesia using standard technique of cold dissection with a snare. Any bleeding event was recorded. The severity of post-operative hemorrhage was classified in five grades. RESULTS: In 11 (2.70%) of the patients grade 1 hemorrhage following tonsillectomy occurred, 4 (0.98%) had grade 2 and 2 (0.49%) of the patients had grade 3 post-operative bleeding. Grades 4 and 5 were not recorded, and no patient received a blood transfusion. CONCLUSION: Post tonsillectomy hemorrhage can be expected in a small number of patients undergoing tonsillectomy. Hemorrhage is mostly primary and rarely requires treatment under endotracheal anesthesia and blood transfusion. PMID- 22779296 TI - Infected total knee arthroplasty treatment outcome analysis. AB - BACKGROUND/AIM: Infected total knee arthroplasty (TKA) is a topic of great importance, because its diagnosing and treatment requires a lot of resources, and often has an unsatisfactory outcome. The aim of this study was to analyze the outcome of the treatment of infection developed following TKA. METHODS: This retrospective study of infected TKAs was performed in the period from 1998 to 2008 in the Orthopedics & Traumatology Clinic of the Military Medical Academy (MMA) in Belgrade. A total of 654 primary and revised TKAs were performed in the said period. We registered and surgically treated 28 infected TKAs (primary TKAs: MMA--22, other institutions--6). The incidence of TKA infection in the MMA was 3.36%. The most common pathogens were: Staphylococcus aureus--14 (50%) cases, and Staph. epidermidis--3 (10.7%) cases. Other isolated pathogens were: Enterococcus faecalis, Klebsiella pneum., Klebsiella spp., Streptoccocus viridans, Seratia spp, Micrococcus luteus and Peptostreptococcus spp. In one case we had mixed anaerobic flora, and in 3 cases cultures were negative. We analyzed diagnostic challenges, risk factors (such as age and previous viscosupplementation) and treatment outcomes in our series of infected TKAs. RESULTS: In our series 2 infections healed after iv antibiotics and debridement, 1 patient responded to open debridement with component retention, 4 patients responded fully to one stage reimplantation, 10 cases responded fully to two-stage reimplantation, 11 patients ended with arthrodesis and we had 1 patient withabove knee amputation. CONCLUSION: Two-stage reimplantation remains gold standard for treatment of infected TKA, and we recommend it as treatment of choice for eradication of infection. The antibiotic loaded spacer prothesis concept in most cases allows infection eradication, good function and high patient satisfaction. PMID- 22779297 TI - [Neuropsychological assessment and treatment possibilities of cognitive deficit in schizophrenic patients]. PMID- 22779298 TI - Life-saving percutaneous coronary interventions on the unprotected left main coronary artery in patients with acute coronary syndrome in the catheterization laboratory without cardiosurgical back-up. AB - INTRODUCTION: The optimal revascularization strategy for unprotected left main coronary disease (ULMCD) is the subject of ongoing debate and patients with ULMCD still represent a challenge for interventionalist, especially in the setting of an acute coronary syndome (ACS). CASE REPORT: We presented two cases of percutaneous treatment of ULMCD in the settings of ACS (ST Segment Myocardial Infarction and Non ST Segment Myocardial Infarction--STEMI and NSTEMI) in a catheterization laboratory without back-up of cardiosurgical department. Both patients were hemodynamically unstable with clinical signs of cardiogenic shock. Coronary angiography revealed left main thromobosis and using intra-aortic balloon pump as hemodynamic support primary angioplasty procedures were performed. Immediately after the procedures the patients hemodynamically improved and remained stable till discharge from hospital. CONCLUSION: Percutaneous coronary intervention (PCI) has become the most common strategy of revascularization in ACS patients with ULMCD and is generally preferred in patients with multiple comorbidities and/or in very unstable patients. In cases with no cardiosurgical departments PCI is an inevitable, bail-out, life saving procedure. PMID- 22779299 TI - [Whipple's disease: a case report]. AB - INTRODUCTION: Whipple's disease is a chronic, multisystem, infectious disease caused by Tropheryma whipplei. It most commonly affects Caucasian males, middle aged. Morbus Whipple is primarily gastrointestinal disease, manifested as malabsorption syndrome, and diagnosed by endoscopy and intestinal biopsy. Extraintestinal manifestations are not rare. CASE REPORT: A 48-year-old male was admitted due to diarrhea, weight loss and weakness in the extremities. Physical examination findings pointed out diffuse hyperpigmentation, pleural effusion and leg edema. Anemia, inflammatory syndrome and malabsorption signs were discovered through laboratory tests. The diagnosis was confirmed by intestinal biopsy. The patient was treated with antibiotic and symptomatic therapy. After 9 months, the patient had no symptoms, and clinical and laboratory findings were regular. CONCLUSION: Whipple's disease is a rare disease. A high degree of clinical suspicion for the disease (malabsorption, arthritis, fever, neurological symptoms) is the most important for diagnosis. Timely diagnosis and appropriate therapy prevent the disease progression and fatal outcome. PMID- 22779300 TI - Could it have been better? A patient with peripartum cardiomyopathy treated with conventional therapy. AB - INTRODUCTION: Peripartum cardiomyopathy is a life threatening condition of unknown cause that occurs in previously healthy women. It is characterized by symptoms of heart failure due to left ventricular dysfunction that occurs in the last month of pregnancy or the first five months after delivery. CASE REPORT: We presented woman who underwent caesarean section due to preeclampsia. Two weeks after delivery first signs of heart failure appeared and only after six weeks following the onset of symptoms peripartal cardiomyopathy was recognized. A conventional treatment with diuretics, ACE inhibitor and beta blocker along with anticoagulant therapy was applied, which resulted in a complete recovery of the left ventricular function four months after. CONCLUSION: Timely detection and initiation of treatment are an important precondition for the complete or partial recovery. PMID- 22779301 TI - The role of autofluorescence bronchoscopy in monitoring a tumorous lesion in the bronchial mucosa: a case report. AB - INTRODUCTION: Autofluorescence bronchoscopy (AFB) is a diagnostic procedure that is included in all diagnostic algorithms discovering precancerous lesions in the large airways. CASE REPORT: We presented a 71-year-old patient submitted to exploration due to prolonged cough. Both noninvasive and invasive pulmonary diagnostic management was carried out. On bronchoscopy, an endobronchial mass was detected in the apical bronchus. A positive endoscopy finding indicated AFB which disclosed a fluorescence alteration of the tumor mucosa and the former bronchoscopy site. Histopathological analysis of the catheter biopsy obtained samples from the right upper lobe confirmed fibrinous purulent pneumonia in organization. The applied treatment resulted in regression of both symptoms and the lesion in the right upper lobe. Due to a positive AFB finding, the patient was regularly observed over the following three years, having had three control AFB to monitor the initial finding. CONCLUSION: AFB may be utilized in the routine of everyday practice to assess the spread of the disease, as well as in the postsurgical and long-term follow-up of operated patients. The procedure may also be applied to enable an easier and more reliable observation of patients with suspicious endobronchial lesions, smokers with altered fluorescence of the bronchial mucosa, and chronic patients. PMID- 22779302 TI - Nitrofurantoin-induced immune-mediated lung and liver disease. AB - INTRODUCTION: Nitrofurantoin, a furan derivative, introduced in the fifties has widely been used as an effective agent for the treatment and prevention of urinary tract infections (UTI). Spectrum of adverse reactions to nitrofurantoin is wide, ranging from eosinophilic interstitial lung disease, acute hepatitis and granulomatous reaction, to the chronic active hepatitis, a very rare adverse effect, that can lead to cirrhosis and death. CASE REPORT: We presented a 55-year old female patient with eosinophilic interstitial lung disease, severe chronic active hepatitis and several other immune- mediated multisystemic manifestations of prolonged exposure to nitrofurantoin because of the recurrent UTI caused by Escherichia coli. We estimated typical radiographic and laboratory disturbances, also restrictive ventilatory changes, severe reduction of carbon monoxide diffusion capacity and abnormal liver function tests. Lymphocytic-eosinophylic alveolitis was consistent with drug-induced reaction. Hepatitis was confirmed by liver biopsy. After withdrawal of nitrofurantoin and application of high dose of glicocorticosteroids, prompt clinical and laboratory recovery was achieved. CONCLUSION: Adverse drug reactions should be considered in patients with concomitant lung and liver disease. The mainstay of treatment is drug withdrawal and the use of immunosuppressive drugs in severe cases. Consideration should be given to monitor lung and liver function tests during long term nitrofurantoin therapy. PMID- 22779303 TI - [Dr Andreas Gruentzig--more than 30 years of the genius vision in therapy of coronary artery disease]. PMID- 22779304 TI - Acute hypobaric-hypoxia challenge and salivary cortisol and DHEA-S in healthy male subjects. AB - BACKGROUND: Hypobaric hypoxia is a stressful emergency situation that can cause a degradation of the sensory, motor, and higher cognitive functions necessary for safe flight. METHODS: We studied the salivary cortisol and dehydroepiandrosterone sulfate (DHEA-S) concentrations of 12 healthy male military aviators (AV) exposed to an altitude-induced hypoxia challenge in a hypobaric chamber. A matched control group (C) of eight flight physiology instructors wearing oxygen masks during the challenge was studied. Salivary samples were collected every 2 h on 3 experimental days (the day before, the day of, and the day after the hypobaric chamber challenge). RESULTS: In the AV group, salivary cortisol concentrations showed a statistically significant increase from 5.42 +/- 0.15 measured at 08:30 to 11.37 +/- 1.86 ng ml(-1) during the hypobaric chamber challenge and a statistically significant increase in DHEA-S was also measured (from 3.15 +/- 0.42 ng x ml(-1) at 08:30 to 5.99 +/- 0.15 ng x ml(-1)). The day after the challenge, the concentrations of both hormones were comparable to those measured the day before; neither C nor AV showed any disturbances of the physiological diurnal fluctuations of cortisol and DHEA-S. No differences were found among the cortisol/DHEA-S ratios measured during the 3 experimental days in the AV group. DISCUSSION: In spite of having experienced a psycho-physical stress, the AVs did not show any dysregulation of the diurnal fluctuations of cortisol and DHEA-S, thus presenting a good level of stress resilience. Data presented in this paper are consistent with recent literature suggesting a stress-buffering role of DHEA S. PMID- 22779305 TI - Gender influence on the performance of chest compressions in simulated hypogravity and microgravity. AB - INTRODUCTION: In the event of a cardiac arrest during microgravity exposure, external chest compressions (ECCs) which form the main part of basic life support should be carried out while the advanced life support equipment is being deployed. This study was aimed to determine if there was any gender difference in the effectiveness of performing ECCs using a body suspension device to simulate lunar and Martian hypogravity and microgravity. METHODS: The volunteers performed ECCs during simulated microgravity (using the Evetts-Russomano method): lunar, Martian, and Earth/Control. Each volunteer performed 3 sets of 30 compressions with 6 s rest in between. The volunteers had their increase in heart rate measured and used the Borg scale to rate the intensity of work after each protocol. RESULTS: The mean depth compressions for men during all gravitational simulations were higher than the women, but both sexes performed effective ECCs during the two tested hypogravity states. During simulated microgravity, men performed significantly deeper ECCs (mean +/- SD of 45.07 +/- 4.75 mm) than women (mean +/- SD of 30.37 +/- 4.75 mm). None of the women achieved the required mean depth of ECCs. Though the increase in heart rate was higher in women, no significant difference was seen in the Borg scale scores between genders during or after the performance of ECCs in microgravity. DISCUSSION: The results suggest both genders can perform effective ECCs during simulated hypogravity. Women, however, cannot perform effective ECCs during microgravity simulation. These findings suggest that there is a gender difference when performing the Evetts Russomano method. PMID- 22779306 TI - Heat acclimation and performance in hypoxic conditions. AB - INTRODUCTION: Hypoxia is known to reduce performance. Adaptation is limited and requires special conditions. Heat and hypoxia have been shown to share some adaptive mechanisms. The purpose of this study was to test the possibility that prior heat acclimation may preserve performance under hypoxia. METHODS: Eight young healthy men participated in this study. They went through two cognitive tests: Visual Vigilance Task (VVT) and Four Choice Reaction Time (FCRT); through a Dynamic Posture Test (DPT); and through an exercise onset of blood lactate accumulation rate (OBLA) test under moderate hypoxia (O2 = 15.6%) before and after 12 d of heat acclimation. RESULTS: Maximal heart rate and core temperature were lower during the last day of heat acclimation compared to baseline (103 +/- 14 compared to 115 +/- 13 bpm and 37.59 +/- 0.20 compared to 37.83 +/- 0.28 degrees C, respectively). OBLA was higher after heat acclimation under both normoxic and hypoxic conditions. Blood oxygen saturation during walking at a pace of 7 km/h in hypoxic conditions was higher after heat acclimation compared to baseline (88 +/- 2% and 86.5 +/- 2%, respectively). Average steps during DPT in hypoxic conditions increased from 4.083 +/- 0.044 to 4.75 +/- 0.326 after heat acclimation. The VVT results under hypoxia did not change after heat acclimation, but false positive results were lower. The FCRT test results improved after heat acclimation (475 +/- 30 ms compared to 500 +/- 24 ms). CONCLUSIONS: Prior heat acclimation may reduce physiological strain and improve cognitive performance in moderate hypoxia. Further studies are required in order to evaluate the possibility of implementing this method as an operational preconditioning tool. PMID- 22779307 TI - Galvanic vestibular stimulation and the ability to maintain arm-hand posture. AB - INTRODUCTION: Vestibular illusions are the most common illusions that can cause spatial disorientation in flight. This study aims to find out whether and how the ability of keeping arm-hand posture is affected by the vestibular illusions induced by galvanic vestibular stimulation (GVS). METHODS: With their heads and trunks firmly fixed, 16 subjects maintained arm-hand posture under three GVS conditions (no stimulation, anode right, and anode left) for 10 s. Range of sway (RS), root mean square of displacement (RMS), and mean deviation (D) of the hand, as well as the rotation angle of the wrist, elbow, and shoulder in the horizontal plane, were measured. One-way ANOVA was used to analyze the effects of GVS on keeping arm-hand posture. RESULTS: With GVS, the hand deviated to the anode side continuously in the lateral direction, but moved at random in the sagittal direction. RS and RMS in the lateral direction were significantly increased by 89.0% and 104.7%, respectively. D was significantly increased about 6 mm to the anode. The shoulder joint and elbow joint always turned toward the anode, but the wrist joint turned at random. Furthermore, GVS polarity had no significant effect on the amplitude of each parameter. CONCLUSION: GVS can decrease both the accuracy and precision of hand position, especially in the lateral direction. The continuous hand deviation to the anode side is mainly induced by the rotation of elbow and shoulder. Extra attention needs to be paid to these findings in future spatial disorientation studies. PMID- 22779308 TI - Cardiovascular drift and Vo2max during cycling and walking in a temperate environment. AB - INTRODUCTION: Different muscle recruitment patterns during cycling and walking may influence the magnitude of cardiovascular drift (CV drift) during these respective modes of exercise, but whether this also influences the magnitude of reduced maximal oxygen uptake (Vo2max) associated with CV drift is unknown.This study tested the hypothesis that cycling results in greater CV drift and a greater decrement in Vo2max than walking in a temperate environment. METHODS: CV drift was measured in nine recreationally active women (ages = 23 +/- 2 yr, Vo2max = 43.0 +/- 5.5 ml x kg(-1) x min(-1)) between 15 and 45 min of cycling or walking at 60% Vo2max on Separate occasions in 22 degrees C, 44% relative humidity. A graded exercise test to measure Vo2max was performed immediately after the submaximal exercise bout with no cessation of exercise. During separate trials involving each exercise mode, Vo2max was measured after 15 min of submaximal exercise so that changes in Vo2max between 15 and 45 min of exercise could be assessed between the same points in time in which CV drift occurred. RESULTS: Across both conditions, heart rate (HR) increased 5.4% and stroke volume (SV) decreased 11% from 15 to 45 min, but Vo2max was not significantly affected (7% reduction; 2.70 +/- 0.5 L min(-1) vs. 2.52 +/- 0.6 L min(-1)). CONCLUSION: In a temperate environment, a small CV drift corresponds to a small, non-significant decrease in Vo2max, regardless of whether the exercise performed is cycling or walking. PMID- 22779309 TI - Local intravascular pressure habituation in relation to G-induced arm pain. AB - BACKGROUND: During high +Gz loads, pilots may experience arm pain. It is commonly assumed that such pain is caused by distension of blood vessels and that vascular distensibility adapts to the prevailing transmural pressure. The aim was to investigate whether vascular pressure habituation (PH) is as efficient in alleviating G-induced arm pain as using counterpressure/support garments. METHODS: In Series I, 7 subjects underwent a 5-wk PH regimen, consisting of 15 40 min sessions, during which intravascular pressures in one arm were elevated by 65 105 mmHg. Before and after PH, arm pain was determined during incremental +Gz exposures in a centrifuge. In Series II, the effect on G-induced arm pain of wearing protective garments around the lower part of the upper arm was investigated in 10 subjects in 4 conditions: 1) counterpressure; 2) rigid support; 3) sham support; and 4) no support (control). Pain was rated using a 10 point graded scale. RESULTS: PH reduced arm pain at 7.5 G from [median (range)] 4 (2-9) to 2 (0-5) in the pressure-habituated arm. The sham support did not affect pain compared to in the control condition (5.2; 3.0-10.0), whereas pain was reduced by both the rigid support (3.7; 1.0-8.0) and the counterpressure (2.5; 0.0-5.5). PH was as efficient in alleviating pain as the counterpressure and more efficient than the rigid support. DISCUSSION: The results support the notion that G-induced arm pain is caused by vascular overdistension. Repeated moderate elevations of local intravascular pressure reduce G-induced arm pain, presumably because such PH reduces vascular distensibility. PMID- 22779310 TI - Pulmonary artery pressure increases during commercial air travel in healthy passengers. AB - BACKGROUND: It is not known whether the mild hypoxia experienced by passengers during commercial air travel triggers hypoxic pulmonary vasoconstriction and increases pulmonary artery pressure in flight. Insidious pulmonary hypertensive responses could endanger susceptible passengers who have cardiopulmonary disease or increased hypoxic pulmonary vascular sensitivity. Understanding these effects may improve pre-flight assessment of fitness-to-fly and reduce in-flight morbidity and mortality. METHODS: Eight healthy volunteers were studied during a scheduled commercial airline flight from London, UK, to Denver, CO. The aircraft was a Boeing 777 and the duration of the flight was 9 h. Systolic pulmonary artery pressure (sPAP) was assessed by portable Doppler echocardiography during the flight and over the following week in Denver, where the altitude (5280 ft/1610 m) simulates a commercial airliner environment. RESULTS: Cruising cabin altitude ranged between 5840 and 7170 ft (1780 to 2185 m), and mean arterial oxygen saturation was 95 +/- 0.6% during the flight. Mean sPAP increased significantly in flight by 6 +/- 1 mmHg to 33 +/- 1 mmHg, an increase of approximately 20%. After landing in Denver, sPAP was still 3 +/- 1 mmHg higher than baseline and remained elevated at 30 +/- 1 mmHg for a further 12 h. CONCLUSIONS: Pulmonary artery pressure increases during commercial air travel in healthy passengers, raising the possibility that hypoxic pulmonary hypertension could develop in susceptible individuals. A hypoxia altitude simulation test with simultaneous echocardiography ('HAST-echo') may be beneficial in assessing fitness to fly in vulnerable patients. PMID- 22779311 TI - Differences in cardio-ventilatory responses to hypobaric and normobaric hypoxia: a review. AB - The presence of differences in physiological response to a lowered inspired Po2 mediated by hypobaric hypoxia (HH) or normobaric hypoxia (NH) is controversial. This review examines the brief, acute, and subacute respiratory, cardiovascular, and subjective symptom response to intermediate and severe hypoxic exposure in NH and HH. Brief exposures lead to similar physiological responses; this is not the case in acute/subacute exposures. Extrapolating data from NH studies to HH in longer exposures is inappropriate as physiological responses to hypoxia seem to be influenced by the prevailing ambient pressure, especially in chronic exposures where acute mountain sickness severity is greater in HH than NH. Explanations for the discrepancy between the two modalities include differences in ventilatory patterns, alveolar gas disequilibrium, and dissimilar acute hypoxic ventilatory responses. Awareness and consideration of these key differences between NH and HH is essential to their proper application to kinesiology, altitude, and aviation medicine. PMID- 22779312 TI - Cognition enhancement by modafinil: a meta-analysis. AB - INTRODUCTION: Currently, there are a number of pharmaceuticals available that have potential to enhance cognitive functioning, some of which may ultimately be considered for such use in military operations. Some drugs with potential for cognition enhancement have already been studied for use in military operations specific to their primary effect in sleep regulation (i.e., dextroamphetamine, modafinil, caffeine). There is considerable information available on many of these drugs. However, considerations for military appropriateness must be based on proficient research (e.g., randomly controlled trial design). METHODS: A meta analysis was conducted to summarize the current state of knowledge of these potentially cognition-enhancing drugs. The analysis only included studies which met inclusion criteria relevant to military research. RESULTS: The results of the literature review reveal a gap in research of the enhancement properties of the drugs of interest. The results yielded three studies (all of which studied modafinil) that met the criteria. The meta-analysis of these three studies revealed a relatively weak pooled effect of modafinil on some aspects of cognitive performance in normal, rested adults. DISCUSSION: While the results of this study support the efficacy of modafinil, the main finding is the large literature gap evaluating the short- and long-term effects of these drugs in healthy adults. PMID- 22779314 TI - Pneumatic muscle actuator (PMA) task-specific resistance for potential use in microgravity exercise. AB - INTRODUCTION: A pneumatic muscle actuator (PMA) is a device that mimics the behavior of skeletal muscle by contracting and generating force when activated. This type of actuator has a high power to weight ratio and unique characteristics which make it ideal for human interaction. PMAs, however, are difficult to control due to nonlinear dynamics. Our objective was to control a PMA as a source of task-specific resistance in simulated isokinetic strength training. Task specific resistance will benefit those in need of strength training through a joint's range of motion, including astronauts who need to counteract muscle atrophy during prolonged spaceflight. The lightweight, clean, and compact PMA driven by pressurized air is able to produce resistance in microgravity. METHODS: An open-loop control method based on a three-element phenomenological inverse model was developed to control the PMA. A motor was simultaneously controlled to act as simulated human quadriceps working against the PMA-produced resistance. RESULTS: For ankle weight replacement resistance profiles, the PMA control method produced resistance and PMA displacement tracking errors (RMSE) of 0.36-1.61 Nm and 0.55-1.59 mm, respectively. Motor position (simulated joint angle) tracking errors ranged from 0.47 to 2.82 degrees. DISCUSSION: Results indicate that the inverse model based control system produces task-specific PMA resistance and displacement. Closed-loop motor control was able to simulate isokinetic movement successfully. More complicated resistance profiles reveal the need for closed loop control. Future work focuses on advancing both the PMA control strategies and the capabilities of the human simulator so that actual human operator applications can be realized. PMID- 22779313 TI - Outcome measure to assess head-down bed rest subject performance. AB - BACKGROUND: The purpose of the present study was to develop an objective outcome measure to assess the performance of head-down bed rest subjects. The rationale behind the development was that the current outcome measure is subjective and dependent upon how much the clinical psychologist knows about subject behaviors during the study to rate them accurately. METHODS: The behaviorally anchored rating scales (BARS) were developed through the use of the critical incident technique, along with traditional BARS development procedures, and the use of focus groups. RESULTS: Use of these methodologies yielded 86 usable critical incidents, which were used as anchors for the scales. DISCUSSION: Further research will be necessary to determine whether or not associations exist between data from the BARS and psychological screening data. PMID- 22779315 TI - Back symptoms in aviators flying different aircraft. AB - INTRODUCTION: Back pain is a common complaint among military aviators of various aircraft. We attempted to define the epidemiologic characteristics of this complaint in military aviators of the Israeli Air Force. METHODS: Aviators of various aircraft (fighter, attack helicopter, utility helicopter, and transport and cargo) completed 566 questionnaires. The questionnaires included various demographic variables as well as questions specifically addressing type of aircraft, location, and severity of pain. Questionnaires were analyzed according to aircraft type, weekly and total number of flight hours. RESULTS: Back pain was significantly more common among utility and attack helicopter pilots. Compared with only 64.02% of fighter pilots, 89.38% of utility and 74.55% of attack helicopter pilots reported some degree of back pain. Cervical region pain was more common among fighter pilots (47.2%) and utility helicopter pilots (47.3%) compared with attack helicopter (36.4%) and transport (22.3%) pilots. Cervical region pain of moderate-severe degree was more common among utility helicopter pilots (7.1%). Mid and low back pain at all degrees of severity were more common among helicopter pilots. A significant proportion of subjects suffered from pain in multiple regions, particularly among utility helicopter pilots (32.74%). Severity of pain was graded higher in all three regions (cervical, mid, and lower back) in utility helicopter pilots. CONCLUSIONS: Utility helicopter pilots have more prevalent and more severe back pain than pilots of other platforms. Yet, it is difficult to make a clear association between type of aircraft and the region of back pain. PMID- 22779316 TI - Atrial fibrillation in two jet pilots during aircrew periodical medical examination. AB - BACKGROUND: Atrial fibrillation (AF) unfavorably affects cardiac output and may cause acute incapacitation in flight due to loss of the atrial systole, which mainly contributes to the diastolic filling of the ventricles. Although it is the most common type of arrhythmia, it is rare in pilots and not compatible with aviation. CASE REPORTS: We present two AF cases incidentally detected in two jet pilots. The first case was a 39-yr-old male jet pilot with a lone AF. Since there was no structural abnormality or thrombus in the left atrial appendage on transesophageal echocardiography (TEE), the patient was converted to sinus rhythm via direct current cardioversion (DCC). The pilot returned to flying duties after a follow-up period without any recurrent arrhythmia. The second case was a 23-yr old male jet pilot who had suffered six attacks of paroxysmal AF. Conversion to sinus rhythm was provided by DCC at once and the second via pharmacological cardioversion. Also, spontaneous conversion to sinus was observed during two attacks of AF during the follow-up period. There were no abnormalities on physical examination, echocardiography, and laboratory tests. Although the cardiac ablation procedure was applied, the patient couldn't be treated successfully. Thereafter the pilot was treated with sotalol and warfarin and was permanently disqualified from flying duties. DISCUSSION: Arrhythmia is among the frequent causes for aviators to be disqualified from flying duties. AF particularly should not be overlooked due to its potential for sudden incapacitation during flight via acute hypotension or thromboembolic events. PMID- 22779317 TI - High performance computing in aerospace medicine. PMID- 22779318 TI - You're the flight surgeon: allergic fungal sinusitis: nasal polyps with R upper lobe cavitary lesion. PMID- 22779319 TI - You're the flight surgeon: renal stones and bladder cancer. PMID- 22779320 TI - This month in aerospace medicine history. PMID- 22779321 TI - Applicability of the vocal tract discomfort (VTD) scale in evaluating the effects of voice therapy of occupational voice disorders. AB - BACKGROUND: Occupational voice disorders are characterized by rich symptomatology, which is dominated by symptoms by the vocal tract discomfort. Therefore, in the management it is important to consider these subjective complaints. The aim of the study was to assess the usefulness of using the vocal tract discomfort scale (VTD) in evaluating the effects of rehabilitation concerning occupational dysphonia. MATERIAL AND METHODS: The study included 55 teachers (mean age: 47.2) with occupational dysphonia diagnosed by means of videostroboscopy. The test battery covered also: voice self-assessment according to voice handicap index (VHI), perceptual GRBAS scale and the new VTD scale. Each subject underwent intensive rehabilitation, including voice training and voice hygiene education. The post-therapy examination was conducted using the above mentioned methods. RESULTS: Comparing the results obtained in the preliminary and the control test a significant post-therapy improvement (p = 0.000) was discovered in relation to the general outcome of the symptoms in the VTD scale-- assessed both as for the frequency subscale (24.7 points vs. 10 points) and the severity subscale (25.5 points vs. 10 points). A positive significant effect of the treatment was also observed in the voice VHI disability index (p < 0.05) and in perceptual voice evaluation, using the GRBAS scale (p < 0.05). In addition, the study revealed a high coefficient of correlation (r) between the subscales of the VTD, both in the preliminary examination (r = 0.934) and the control one (r = 0.935). CONCLUSIONS: The vocal tract discomfort scale (VTD) seems to be a valuable tool, useful in monitoring the progress in the treatment of occupational voice disorders. PMID- 22779322 TI - [Harmful biological agents at museum workposts]. AB - BACKGROUND: The aim of the studies was to determine the level and kind of microbiological contamination of air and surfaces in museum premises with various collection specificities. In addition, the criteria for selecting indicators of contamination with harmful biological agents at museum workposts are proposed. MATERIAL AND METHODS: The analysis of microbial contamination was carried out in 14 museum premises (storehouses, restoration workshops, exhibition hall). Microbiological air purity was measured with a MAS-100 Eco Air Sampler. Surface samples were collected using contact plates RODAC Envirocheck. Biochemical API tests were used to identify bacteria and yeasts. Fungi were diagnosed with taxonomic keys, based on macro- and microscopic mycelia assessment. RESULTS: The levels of microbiological contamination in museums varied and ranged from 2.1 x 10(2) to 7.0 x 10(3) cfu/m3 in the air and from 1.4 x 10(2) to 1.7 x 10(4) cfu/100 cm2 on surfaces. The dominant microorganisms were fungi, which accounted respectively for 18-98% and 23-100% of all isolates from tested sites and surfaces. It was found that the amount of fungi in the indoor air of the Museum of Archeology and Ethnography and the Museum of Independence Traditions equaled respectively 4.2 x 10(2) cfu/m3 and 1.4 x 10(4) cfu/m3, which means that they exceeded the recommended reference value of 2.0 x 10(2) cfu/m3. CONCLUSIONS: Having analyzed the frequency of strain isolation, the source of microorganisms and the hazard to human health, 10 fungal species were isolated, which may be regarded as indicators of contamination with harmful biological agents at museum workposts. They are: Aspergillus (A. niger, A. versicolor), Cladosporium (C. herbarum, C. macrocarpum), Penicillium (P. carneum, P. digitatum, P. italicum, P. paneum, P. polonicum), Rhizopus nigricans. PMID- 22779323 TI - [Identification of the effects of certain determinants on the results of pension prevention in the locomotor dysfunction]. AB - BACKGROUND: A large group of patients of Ladek Zdroj spa consists of people with disabilities confirmed by objective tests performed under the pension prevention program of the Social Insurance Institution (ZUS). The purpose of disability prevention is to improve the health conditions to the extent required to continue work. The aim of the study was to identify the differences in the assessment of the treatment and its results between patients referred by the Social Insurance Institution and by the National Health Fund (NFZ). MATERIAL AND METHODS: A group of 780 people referred to the spa treatment because of different locomotor dysfunctions participated in a questionnaire-based voluntary anonymous survey. The control group consisted of 215 persons with similar illnesses referred by the National Health Fund. The questionnaire included nine specific questions concerning important socio-medical issues of spa rehabilitation. RESULTS: Following the mathematical analysis, the survey data, presented in the percentage form in 10 tables, allowed us to identify differences in the evaluation of treatment of patients referred by ZUS and NFZ. CONCLUSIONS: Satisfactory results of rehabilitation were reported more often by patients referred by NFZ than by those treated under the ZUS disability prevention program. The latter group of patients frequently reported anger, fear or despair associated with rehabilitation declaring at the same time active participation in the treatment process. This observation provides evidence that the pension prevention based on the holistic model, preferred by the Social Insurance Institution, is more useful. PMID- 22779324 TI - [Application of infrared spectrometry (FT-IR) for mineral identification of asbestos in bulk samples]. AB - BACKGROUND: The aim of this study was to apply infrared spectrometry (FTIR) in mineral identification of asbestos in bulk materials. MATERIAL AND METHODS: The identification of asbestos was based on infrared spectra of UICC and NIST: SRM 1866a and SRM 1867 standard asbestos, and infrared spectra of heat treatment chrysotile, crocidolite and amosite asbestos. The samples of bulk materials were grinded and fibers were isolated from samples. The KBr disc standard technique was used in the preparation of samples for infrared measurements. The infrared spectra were recorded in transmittance function, at resolution of 4 cm1 and for 32 averaged scans. RESULTS: The analysis of the infrared spectra revealed that chrysotile, crocidolite, amosite and anthophyllite asbestos can be identified in industrial products and distinguished in mixtures. Spectra of fibrous materials do not interfere with spectra of asbestos. When analyzing the whole sample mass, interferences from the components of construction materials can be eliminated or reduced by using computer transforming spectra, preliminary purification of samples or separation of sample components. The method used permit to identify from 2 to 4 microg of the three basic forms of asbestos. Spectra of chrysotile and amosite heated to 500 degrees C and crocidolite heated to 300 degrees C are the same as non-heated forms. Heating in higher temperature induces characteristic changes in spectra and the transformation of asbestos into other minerals. CONCLUSIONS: Infrared spectrometry can be used for routine identification of asbestos in samples of bulk materials also treated with high temperature, and to assess the effectiveness of asbestos waste detoxification. PMID- 22779325 TI - [Exposure to respirable asbestos fibers at various stage of asbestos removal work]. AB - BACKGROUND: Damaged asbestos-containing materials are the source of asbestos fibers released into the outdoor or indoor environment. The highest risk concerns asbestos removal workers, and also other people staying near the performed work. The aim of this project was to analyze and assess air concentrations of asbestos fibers in different types of buildings with asbestos-containing elements under normal operation, as well as during demolition, renovation and maintenance work. MATERIAL AND METHODS: Air samples were collected using stationary and individual aspirators from the breathing zone of people at different locations. The concentration of respirable fibers was determined in accordance with Polish Standard PN-88 Z-04202/02. Air sampling was carried out inside buildings before and during removal of asbestos products, as well as in ambient and indoor air after completing dismantling and repair works. RESULTS: The analysis included 2925 measurements carried out during 2003-2010. Concentrations of respirable asbestos fibers in buildings containing asbestos installations, during their normal operation ranged from 0 to 0.0043 fiber/cm3. Measurements taken at the workposts during removal of asbestos-cement materials showed the average asbestos fiber concentrations of 0.0652 fiber/cm3 and 0.0141 fiber/cm3 for work carried out inside and outside the buildings, respectively. CONCLUSIONS: The concentrations of asbestos respirable fibers inside the buildings containing asbestos elements were low, far beyond the hygiene standard. The highest concentrations of asbestos fibers and the highest percentage of the measurement results exceeding hygiene standard were found at the workposts inside buildings during asbestos removal. PMID- 22779326 TI - [The relationship between workaholism defined as an addiction and a behavioral tendency and work-family conflict]. AB - BACKGROUND: The aim of this research was to analyze the relationship between workaholism (defined as an addiction and a behavioral tendency) and intensity of work/family conflict (WFC/FWC). MATERIAL AND METHODS: A group of 178 employees was surveyed three times in one year: six months before the annual leave, just after its termination and six months after annual leave. The Scale of Being Absorbed by Work (Skala Zaabsorbowania Praca - SZAP) by Golinska was applied to measure workaholism defined as an addiction, and the Scale of Workaholism as Behavioral Tendencies (SWBT) by Mudrack and Naughton to measure workaholism defined as a behavioral tendency. In addition, the Scale of Work-Family Conflict by Netemayer was used as another diagnostic tool. RESULTS AND CONCLUSIONS: The results of the survey showed statistically significant positive relationship between workaholism measured by SZAP and the intensity of work-family conflict (WFC/FWC) at each stage of the study, while workaholism measured by SWBT did not reveal such a relationship. The results indicate a significant role of the applied Scale of Being Absorbed by Work in understanding the effects of workaholism. PMID- 22779327 TI - [Profiles of factors enhancing teachers' occupational wellbeing and their use in health promoting schools]. AB - BACKGROUND: The aim of this article is to present the results of survey on general occupational being and factors contributing to the enhancement of teachers' occupational wellbeing. The authors also address the issue how to work out, analyze, present and use the survey results in health promotion at schools. MATERIAL AND METHODS: Teachers of four selected health promoting schools (HPS) were surveyed and the results were analyzed. The Factors Enhancing Teachers's Occupational Wellbeing Scale was used. This instrument consisted of 45 statements on 5 subscales (working conditions, teachers' community, students' and parents' community, organization and workload, professional competences). They were measured from two points of view, the assessment of a current situation and the assessment of needs for the improvement. The scale was preceded by questions concerning the assessment of general occupational being and the assessment of general occupational being of other teachers at school. RESULTS: The self assessment of the respondents' own and other teachers' occupational being was positive. The current situation related to factors influencing teachers' wellbeing was recognized by teachers as rather good and the need for change was rather low. There were differences between schools in the majority of analyzed factors. An easy method of analyzing data as numerical values and graphic profiles was proposed to be used in HPS. CONCLUSIONS: Factors influencing teachers' occupational wellbeing differed between schools. The results of their assessment should be analyzed in each school taking account of its individual context. The proposed instrument and method of data analysis are useful in the planning of teachers' health promotion projects, diagnosis of the initial status ("pre-test") and evaluation of their outcomes ("post-test"). PMID- 22779328 TI - [Chronic obstructive pulmonary disease--work-related disease]. AB - Chronic obstructive pulmonary disease (COPD) can be induced by hazardous agents present in the work environment. It is estimated that employment in exposure to dust and irritant gases is responsible for 10 to 20% of COPD cases. The paper reviews the etiology (particularly the occupational risk factors) of the disease, its clinical symptoms, and diagnostic procedures. The significance of COPD in occupational medicine, especially in terms of prophylactic care of workers is also presented. PMID- 22779329 TI - [Driving simulators in risk assessment of traffic accident among drivers with obstructive sleep apnea]. AB - Sleep disorders in the form of obstructive sleep apnea (OSA) are still underdiagnosed and insufficiently treated in drivers. This is a very important problem, because chronic sleepiness during the day and episodes of sleep during driving a road vehicle are now regarded as one of the main causes of traffic accidents, including fatal ones, caused by professional drivers. For many years driver fatigue has been considered a major risk factor of traffic accidents, while obstructive sleep apnea has remained almost completely disregarded. In the late 1980s and early 1990s epidemiological data began to indicate sleepiness and sleep deficit as the cause of up to 20% of road accidents. Later studies conducted in many countries in different groups of drivers have confirmed that people with breathing problems during sleep are much more likely to cause accidents than healthy ones. These accidents often result from sleep disorders experienced by drivers while driving, during both long monotonous journeys and in heavy urban traffic. The application of treatment involving continuous positive airway pressure (CPAP) reduces the rate of accidents among drivers. In the recent years, the studies of this problem has been expanded by the use of drive simulators that quite accurately simulate real driving conditions. This approach allows to assess the driver's reactions and behaviors in different situations on the road, including the most dangerous ones. By comparing the results from the simulator with those in real conditions it will be possible to see to what extent the risk of accident in simulated conditions correlates with the risk of accident in real life settings. PMID- 22779330 TI - [Questionnaires for assessment of work-related psychosocial hazards--a review of diagnostic tools]. AB - Holistic management of the organization also covers psychosocial risk management. Gathering information about psychosocial work-related hazards is the first step of the psychosocial risk management. In this process, the identification of the occupational indicators on work-related stress must be done. The paper presents a review of the measures available to assess psychosocial work-related hazards which are available in Poland. The following measures are included: Psychosocial Working Conditions, Effort-Reward Imbalance (ERI), Subjective Assessment Work Characteristics Questionnaire, Objective Work Characteristics Questionnaire, HSE Indicator Tool, Brief Scale of Vocational Stress, questionnaire "Psychosocial Factors" and Questionnaire of Occupational Burdens in Teaching. Besides the basic information about the measures (e.g. scales, examples of items, psychometric parameters), critical assessment of each measure in relation to its usefulness is also provided. The main conclusion is that a well-specified goal of diagnosis and planned intervention is the key issue while choosing a questionnaire. The review of tools available in Poland can be of great help for occupational health and safety professionals, and support them in the work aimed at improvement of psychosocial working-conditions. PMID- 22779331 TI - [Migrant vaccinations in Poland]. AB - After the European Union accession in 2004, Poland has been perceived by foreigners as an attractive destination of their migration, and also as a popular transit country for people going further to the Western Europe countries. The Nofer Institute of Occupational Medicine is involved in the implementation of the international project PROMOVAX (Promote Vaccinations among Migrant Populations in Europe). The objective of the project is to promote immunizations among migrant populations in Europe. This article presents the up-to-date legal regulations that are effective in Poland, taking into account their relevance to the issue of vaccinations in migrant population. The analysis of the Polish legislation concerning this problem shows that there are no specific regulations addressed to migrant population staying in our country. This issue seems to be popular in the European Union, where immunization of migrants is given high priority. From the point of view of health care professionals it is important to be aware of the fact that EU open borders favor the increased flow of people between countries. The scale of migration from outside the EU to its member states also contributes to the increase in potential contacts between health care workers and migrants working in Poland. PMID- 22779332 TI - [Meningococcal infections]. AB - Neisseria meningitidis is responsible for rapid-onset septicaemia and/or meningitis, the conditions that are referred as invasive meningococcal disease (IMD). Although cases of IMD usually appear only sporadically, they may also emerge in outbreaks and large epidemics. Due to epidemic potential, which Poland has been faced particularly in 2006-2007 and possible fulminant course of infection, many countries have established national meningococcal reference centre. Their activity focus on monitoring of IMD epidemiological situation, based on laboratory confirmed cases and possessed knowledge leads to optimal therapeutic and prophylactic decisions. In Poland such function is assigned to the National Reference Centre for Bacterial Meningitis (NRCBM). PMID- 22779333 TI - [Invasive meningococcal disease in Opolskie Voivodeship between 2005-2010]. AB - The article describes epidemiological situation concerning invasive meningococcal disease in Opolskie Voivodeship in comparison to the whole country in years 2005 2010, and activities undertaken related to the increased number of meningococcal infections. Owing to anti-epidemic and educational activities, distinct improvement of epidemiological situation in respect to invasive meningococcal disease in Opolskie Voivodeship was achieved. It required many of interdisciplinary activities and multi stage cooperation between Public Health Institutions. Only closed cooperation and exact realization of Meningococcal Disease Council recommendations and of the National Reference Centre for Bacterial Meningitis procedures permitted to control epidemic situation. Mass media played a significant role providing reliable and timely information and education campaign which allowed to reduce public anxiety in Opolskie Voivodeship. PMID- 22779334 TI - [Early invasive strategy in patients with myocardial infarction and intraventricular conduction disturbances and plasma B-type natriuretic peptide levels assessed 6 months after myocardial infarction]. AB - The aim of the study was to assess plasma B-type natriuretic peptide (BNP) levels in patients after myocardial infarction (MI) with intraventricular conduction defects (IVCD) and to define relationship between BNP level, treatment strategy and left ventricular performance. MATERIAL AND METHODS: Four types of IVCD were noted: left bundle branch block (LBBB), right bundle branch block (RBBB), left anterior hemiblock (LAH) and left posterior hemiblock (LPH). A total of 158 patients six months after MI treated either invasively or conservatively were included. Of them 126 had IVCD (group A): LBBB-31, RBBB-36, LAH-130, LPH-29, whereas 32 patients without IVCD served as controls (group B). Plasma BNP levels were measured using an immunoenzymatic method. All subjects underwent echocardiography to evaluate left ventricular function. RESULTS: In group A significantly lower plasma BNP levels (186.3 vs 355.3 pg/mL; p < 0.01) and significantly higher left ventricular ejection fraction (EF) (48.4 vs 42.4%; p < 0.05) were noted in favour of invasive treatment. In group B differences between plasma BNP level and echocardiographic parameters of left ventricle function were insignificant. In patients with LBBB plasma BNP levels were significantly lower in those treated invasively (163.9 vs 528.9; p < 0.01). Also, left ventricular EF and myocardial performance index (MPI) were comparable, whereas E/A value was lower as compared with patients treated conservatively (p < 0.05). There were no significant differences in BNP levels in groups with RBBB, LAH and LPH. Multifactorial regression analysis showed that BNP levels were most strongly correlated with magnitude of the ejection fraction EF (p < 0.001). Other parameters which affect significantly BNP level were MPI: OR 9.07 (95% CI 1.03 79.58; p < 0.05) and E/A: OR 6.58 (95% CI 1.01-42.76; p < 0.05). CONCLUSIONS: Invasive strategy in MI with IVCD, especially with LBBB, correlates with lower plasma BNP levels six months after index procedure. In patients with IVCD post MI plasma BNP level is better marker of dysfunction of the left ventricle than its ejection fraction. PMID- 22779335 TI - [Sarcoidosis and tobacco smoking--clinical picture, diagnostic tests results and bronchoalveolar lavage fluid composition]. AB - Sarcoidosis is a multiorgan granulomatous disease of unknown aetiology. Bronchoalveolar lavage (BAL) is approved in diagnostics of sarcoidosis. The aim of the study was to assess epidemiological data, demographic status, clinical picture of sarcoidosis patients and to correlate above-mentioned findings with smoking status. MATERIAL AND METHODS: The study included 101 patients hospitalized due to suspicion of pulmonary sarcoidosis. The results of clinical assessment and smoking status data were obtained by retrospective analysis of 78 confirmed sarcoidosis case records. RESULTS: Investigated group comprised 54 non smokers (NS) and 24 smokers (S), including 9 (11.5%) active smokers (AS). Smokers were significantly younger than nonsmokers. Most of the smokers were males. The mean number of pack-years was 8.2. Respiratory symptoms occurred with similar frequency among non-smokers and smokers. The incidence of the Loefgren's syndrome was similar in S and NS . The pulmonary function tests results were comparable in both groups, however, the obstruction was more frequent among smokers. Composition of BAL fluid (BALf) differed significantly between S and NS. The total cell count was significantly higher among active smokers than among nonsmokers (29.3 +/- 19.2 x 10(6) vs 13.7 +/- 6.3 x 10(6)). Compared to non smokers, smokers had higher number of macrophages and lower percentage of lymphocytes (11.3 +/- 11 x 10(6) vs 6.5 +/- 3.9 x 10(6), 29 +/- 19 vs 41 +/- 17%, respectively). CONCLUSIONS: A significantly lower proportion of smokers is observed among sarcoidosis patients than in general population. The influence of smoking on clinical picture and results of pulmonary function tests is not evident in sarcoidosis. However, tobacco smoking causes significant alteration in the composition of BALf, which should be taken into account in diagnostics of sarcoidosis. PMID- 22779336 TI - [Albuminuria in patients with type 2 diabetes mellitus in relation to percentage of HbA1c]. AB - Albuminuria is an early marker of the microvascular and macrovascular complications in patients with type 2 diabetes mellitus. Metabolic complication accompanying the disease, especially hyperglicaemia, have significant influence on the range of albumin excretion. The aim of the study was to evaluate urinary albumin excretion and percentage of glycated hemoglobin (HbA1c), in relation to fasting and postprandial glycaemia. MATERIAL AND METHODS: Research was made in two groups of patients with confirmed albuminuria: in the 1st group with good glycemic control with HbA1c > or = 6,1%-< or = 6,5%, and in the 2-nd group with poor glycemic control with HbA1c > 6,5%-< or = 10%. The control group consisted of 21 patients with essential hypertension and coexisted albuminuria, not suffering from diabetes. The average fasting and postprandial glycemic were calculated for each patient on the basis of the last three values of glycaemia from the patient's self-control test. The extent of albuminuria and the percentage of HbA1c were determined by the immunoturbidimetric test. RESULTS: The highest albumin excretion in urine was noticed in the group with poor glycemic control, a slightly lower level of albuminuria was found in the group with good glycemic control, however the lowest level of albumin excretion was noticed in the control group. The differences were not statistically significant. The fasting glycaemia as well as postprandial glycaemia were increased in the group with higher percentage of HbA1c (p < 0,001) with comparison to the group with good glycemic control. The average percentage of HbA1c was 7,54% in the group with poor glycemic control and was significantly connected with larger glycaemia with comparison to the 2nd group with average percentage of HbA1c 6,3%. CONCLUSIONS: The excretion of albumin in urine rises with increased glycaemia and percentage of glycosylated hemoglobin. Fasting glycaemia as well as postprandial glycaemia have influence on the percentage of glycated hemoglobin. PMID- 22779337 TI - [Gastroduodenal artery selective endovascular embolization in pancreatic pseudo cyst hemorrhage]. AB - The case of massive bleeding from gastroduodenal artery to pancreatic cyst is reported. In the literature there are only a few similar cases reported in the context of their occurrence and treatment. Bleeding was treated with gastroduodenal artery selective endovascular embolization. The article presents the classification, epidemiology and etiopathogenesis of visceral aneurysms. Consequences of aneurysm rupture were also underlined. The article lists different methods that can be used in the treatment of pseudoaneurysm with a specific estimation of endosvascular embolization in bleeding from ruptured aneurysm. The authors stress/ emphasize that arterial endovascular embolization is a mini-invasive and very effective treatment of acute bleeding from ruptured aneurysm in patients suffering from chronic pancreatitis. It allows curing of life-threatening bleedings and avoiding emergency laparotomies during which it is often difficult to find the source of bleeding. In addition, emboliztion may be considered as a preoperative initial procedure that improves general patient status. It allows you to temporarily cover dangerous bleeding and later, to treat electively considering pancreatic pseudocyst. PMID- 22779338 TI - [Rectus sheath hematoma: a rarely diagnosed complication of anticoagulation therapy]. AB - Anticoagulation therapy with vitamin K antagonist (VKA) or heparin, even properly applied, may lead to occurrence of differently localized hematomas, including rectus sheath hematoma (RSH). This uncommon complication of anticoagulation is often misdiagnosed. In the presented case of a 72-year-old man, with a history of VKA use for permanent atrial fibrillation, an additional factor which might predispose to RSH formation was intensive cough during respiratory tract infection. Hematoma was detected with delay on abdominal ultrasonography and visualized topographically on computed tomography Conservative treatment was performed. During a 5-month period, gradual reabsorption of RSH was observed on control ultrasonography examinations. PMID- 22779339 TI - [Usefulness of creatinine and cystatin C in the assessment of renal function in chronic kidney disease and coexisting diseases]. AB - The authors present literature review of usefulness of serum creatinine concentration measurements in comparison with cystatin C concentration for assessment renal function in chronic kidney disease and concomitant diseases. In this article different methods of determining renal filtration are critically discussed. In comparison with creatinine, cystatin C is a good parameter for assessing stable renal function and their early damage. It is a marker of subclinical disorders in chronic renal failure which is also useful in assessing renal dysfunction in coexisting diseases. Cystatin C is more precise than creatinine especially in pediatric, elderly, diabetic and oncological patients. It is more accurate because it is not associated with amount of muscle mass and nutritional status. Among many parameters cystatin C is a promising marker broadening diagnostic tools in nephrology. PMID- 22779340 TI - [Biologic therapy and new therapeutic opportunities in systemic lupus erythematosus]. AB - Systemic lupus erythematosus is a connective tissue disease of unknown origin and unpredictable course. At the moment there is no specific targeted treatment for the disease and corticosteroids are still main therapeutic option. Steroid use, however brings many side effects. Therefore searching for new treatment strategies is at the moment the main challenge for rheumatologists. The potential targets for the treatment include B and T cells co-stimulation molecules and various cytokines. In the paper potential targets for treatment of SLE have been reviewed with the special emphasis to the result of recently finished clinical trials in this indication. PMID- 22779341 TI - [Atypical pituitary tumors]. AB - The significant progress made in recent years, especially in the field of imaging procedures and immunocytochemistry, has caused great improvement in the identification and differentiation of less known pituitary tumours. Thyrotropin (TSH)-secreting adenomas constitute about 1-2% of all pituitary tumours and their presence leads to central hyperthyroidism. This condition is characterised by a diffuse goiter, elevated circulating levels of free thyroid hormones and a nonsuppressed serum TSH. Gonadotropin-secreting tumours in rare cases may result in ovarian hyperstimulation, testicular enlargement or precocious puberty The vast majority of clinically non-functioning pituitary tumours are gonadotroph cell adenomas accounting for 40 to 50% of all pituitary macroadenomas. True non functioning pituitary tumours may cause, as a result of their mass effect, optic chiasm compression or deficient hormone secretion. Transsphenoidal surgery with or without external irradiation is considered the treatment of choice of all the discussed pituitary tumours. This manuscript was aimed to provide an overview of the contemporary etiopathogenesis, diagnosis and treatment of thyrotropin- and gonadotropin-secreting and non-functioning pituitary adenomas. PMID- 22779342 TI - [Antiinflammatory therapy in ostheoarthritis including omega 3 and omega 6 fatty acids]. AB - Osteoarthritis (ostheoarthrosis, OA) is characterized by progressive destruction of articular cartilage, remodeling of the periarticular bone and inflammation of the synovial membrane. In patients occur joints pain, impaired joints motion and disability. The results of many studies indicate an inflammation as foundation of this disease. The management of OA include a combination of pharmacological treatments and nonpharmacological interventions. Pharmacological treatments include used paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs) and chondroprotectives (glucosamine, chondroitin sulfate and so on). NSAIDs long-term use associated with serious adverse effects. OA symptoms are effectively reduced by nutrients such omega 3 and omega 6 fatty acids (PUFAs as EPA, DHA), which decrease the need for non-steroidal drugs and may less adverse events. They exerts, particularly EPA, anti-inflammatory effect, inhibit catabolic processes, stimulate the anabolic process in the cartilage in the joint. Many different evidence validate that omega 3 alleviate the progression of osteoarthritis and have exciting therapeutic potential for preventing cartilage degradation associated with chronic inflammatory in joints. PMID- 22779343 TI - [Current opinions on the etiology and pathophysiology of hirsutism]. AB - Hirsutism, defined as the presence of terminal hairs in females in a male-like pattern, affects approximately 7% of women. It is a manifestation of a variety of disorders, the most common of which is polycystic ovary syndrome. In some cases, however, hirsutism may be the first clinical manifestation of a severe, and even life-threatening, underlying disorder such as an ovarian or adrenal tumour, congenital adrenal hyperplasia, or Cushing's syndrome. In 5 to 15% of hirsute patients with so called 'idiopathic hirsutism' there is no evidence of any disease or detectable androgen excess. Apart from the risk associated with the presence of underlying disorder, hirsutism has by itself a negative psychological impact on a quality of life of the patient. The aim of this overview, based mainly on the recent literature, is to describe in details the pathogenesis of hirsutism and various causes leading to this women's health problem. PMID- 22779344 TI - [Brachial cleft cyst]. AB - Brachial cleft cyst is a congenital anomaly arising from persistent elements of branchial apparatus. It may assume the form of cyst, sinus or fistula and constitutes 30% of all congenital anomalies of the neck region. Brachial cleft cyst is usually recognized in patients before the 5th year of age, but it may appear in patients between 20 and 40, when it enlarges owing to infection. It reveals then as a smooth, resilient tumor in lateral region of the neck. Ultrasonography, computerized tomography and magnetic resonance may be used to evaluate and differentiate these lesions as well as to reveal the presence of fistula, which is important to plan the proper surgical treatment. The only effective treatment is total surgical excision. The lack of treatment puts a patient at risk of infections, while incomplete removal might result in recurrence. PMID- 22779345 TI - [Brain plasticity]. AB - The term "brain plasticity" refers to the brain capability to change in response to the environmental factors. Many of these changes are recorded and stored permanently to be used at a later stage. The concept of brain plasticity is based on assumption that the development of each person's brain is influenced by both physical and psychological experiences. On the systemic level, plasticity is the property of nervous system to adapt, change, self-repair, learn and memorize. This is a common feature of neurons present in each level of nervous system. The concept of brain plasticity therefore has two significant elements: critical periods and changes depending on activity. The notion of critical period means that for some aspects of brain development the time of data reception is crucial and that significant abilities may be lost or limited if no stimulation appears at the right moment. The concept of "activity-dependent learning" shows that changes occurring in brain may also be caused by the influence of psychological, biological or environmental factors. At the basic level organization of cells can change. On higher levels, on dendrites, subsequent branches may ramify, synapses may be formed and the concentration of chemical transmitters may get increased or reduced. PMID- 22779346 TI - [Religiosity and health in epidemiological studies]. AB - The relationship between religion and health has been the subject of growing interest in epidemiological research. The aim of this paper is to review the data on relationship between health-related behaviors associated with religiosity and reduced mortality and morbidity. In this review beneficial effects of religiosity on specific physical and mental health diseases, focusing on coronary heart disease, cancer, depression, suicide, psychosis, and substance abuse are described. Religious beliefs and practices can represent powerful sources of comfort, hope, and meaning and they are associated with protective dietary habits and reduced risk of substance abuse. Religiosity can be also harmful as it is often entangled with neurotic and psychotic disorders. The current published data suggests that religiosity has a favorable effect on survival, although the methodological controversies including presence of biases typical for observational research indicate that results should be interpreted with caution. PMID- 22779347 TI - [Estimation of the arterial blood radioactivity concentration using the whole body-to-arterial blood partition coefficients and the cross-calibration factor in 123I-iodoamphetamine SPECT--towards a noninvasive clinical protocol with the QSPECT-DTARG method]. AB - The aim of this study is to develop a non-invasive procedure for quantitative assessment of regional cerebral blood flow using IMP and SPECT. A technique to utilize a population-based standardized arterial input function has been evaluated for the normal data base obtained from 3 institutions, which employed different SPECT device configurations. In total, data from 39 subjects were analyzed. Due to the unique feature of the QSPECT reconstruction software program, images are quantitative providing units of Bq/ml. Thus, the well counter values can be converted to absolute radioactivity concentration. The blood-to whole-body average partition coefficient was 343.8 +/- 65.0 and did not show significant difference among the three institutions. The estimated blood counts agreed with those assessed by the well counter in all institutions, thus the arterial input function can be estimated with the unique conversion factor for all institutions. This feature may allow a large scale multi-center investigation, which may contribute to improve the non-invasive protocol. PMID- 22779348 TI - [Advances of studies on new technology and method for identifying traditional Chinese medicinal materials]. AB - In this review, the authors summarized the new technologies and methods for identifying traditional Chinese medicinal materials, including molecular identification, chemical identification, morphological identification, microscopic identification and identification based on biological effects. The authors introduced the principle, characteristics, application and prospect on each new technology or method and compared their advantages and disadvantages. In general, new methods make the result more objective and accurate. DNA barcoding technique and spectroscopy identification have their owner obvious strongpoint in universality and digitalization. In the near future, the two techniques are promising to be the main trend for identifying traditional Chinese medicinal materials. The identification techniques based on microscopy, liquid chromatography, PCR, biological effects and DNA chip will be indispensable supplements. However, the bionic identification technology is just placed in the developing stage at present. PMID- 22779349 TI - [Comparison of DNA barcoders in identifying medicinal materials]. AB - The DNA barcoding of traditional Chinese medicine was summarized in this article. Based on analyzing a number of research findings, the authors discussed the possibility of nuclear DNA sequence and chloroplast genes in identifying medicinal materials. ITS was considered to evolve faster, which was used for plant molecular systematics analysis and species identification,while ITS2 was more suitable to identify medicinal materials. So, it is important that we should select suitable DNA sequences as barcodes based on the objective of a study. With the cost reduction of sequencing, identifying medicinal materials by cp-genome barcoding would be applied broadly and effectively in the future. PMID- 22779350 TI - [Application and advantage of near infrared spectroscopy technology in authentication of Chinese materia medica]. AB - This review introduced the application of near infrared spectroscopy (NIRS) in the identification of species, production area and processing method as well as quality evaluation of Chinese materia medica (CMM). By comparing with other authentication methods of CMM, the NIRS technology showed great advantages in exclusive identification of CMM, both identification and quality evaluation of CMM as well as identification of famous-region medicinal material. Finally, the future direction of the authentication of CMM by NIRS technology was suggested. PMID- 22779351 TI - [Advances in identification of Chinese medicines by NIRS]. AB - This review addresses the latest situations and advances of near infrared spectroscopy (NIRS) in which detection of counterfeits and imitations, as well as monitoring origin and quality of Chinese crude drugs and Chinese patent medicines (CCDM) through consultation and summarization of relative literatures. On the one hand, NIRS gradually reveals its advantages and discriminating ability in the ways of nondestructive, rapid, simple, easy, and handy assessment. However NIRS still has some problems in representative samples and models stability for practice of CCDM. In order to keep up with popularization of NIRS in other areas, applications in detection of precious and/or priceless herbals, on-line quality control of valuable herbs, and screening of some chemicals illegally mixed into herbal preparations may be focused preferentially. PMID- 22779352 TI - [Application of bioinformatics in molecular authentication of traditional Chinese medicinal materials]. AB - Benefiting from various DNA technologies, DNA markers have now become a popular means for the identification of Chinese medicinal materials. Facing the huge amount of valuable data that has been produced, researchers need to understand the bioinformatics tools for analyzing the obtained DNA information. This paper summarizes the applications of bioinformatics in molecular authentication of Chinese medicinal materials, including checking phylogenetic information of the samples, searching and retrieving DNA sequence data, matching of similarity between the sequences and performing multiple sequence alignment. PMID- 22779353 TI - [Application of new technologies and methods in morphological and microscopic identification of Chinese materia medica]. AB - Traditional Chinese medicine (TCM) is gaining popularity across the world. The identification of Chinese materia medica (CMM) is vital for assuring safety and efficacy of the products. In this article, new technologies and methods, such as electronic nose, electronic tongue, histochemical localization, fluorescence microscopy, X-ray microscopy in phase contrast, computer image technology, and their application in the morphological identification or microscopic identification of CMM were reviewed. PMID- 22779354 TI - [Progress on chemical pattern recognition in traditional Chinese medicines by multidimensional information of metabolic fingerprinting analysis]. AB - As a comprehensive, quantifiable identification method based on the chemical composition information of traditional Chinese medicine (TCM), the fingerprint of traditional Chinese medicine has become an internationally recognized effective way to control the quality of natural medicine. Chemical pattern recognition in traditional Chinese medicines is an important breakthrough for the infiltration between fuzzy and pharmaceutical sciences, has been used in the field of quality assessment and control for traditional Chinese medicine. It has solved the problem of comprehensive analysis with multi-dimensional information, and gradually been accepted by more researchers to in-depth study in the further. With the development of modern chemical analysis and computer techniques, there are more technologies were applied to the establishment of fingerprints of traditional Chinese medicine, more chemometric methods have been applied to the data processing of TCM fingerprint, and more quality identification and assessment for TCM to be achieved. And the technology has matured and achieved a lot. In this paper, we make a review for the chemical pattern recognition in traditional Chinese medicines since it be invented, provide a reference for the further research. PMID- 22779355 TI - [Several common types of counterfeit and inferior drugs in Chinese medicinal materials market]. AB - Though there are many species of counterfeit and inferior drugs of Chinese Medicinal Materials in the market, the means of fabrication is common. According to our investigating and reports in the literature it is found that the counterfeits and inferior drugs exist in 4 styles: counterfeits, reused medicinal materials and their slices which have been extracted by boiling water or ethanol, medicinal materials and their slices which have been added with non-medicinal parts or chemicals, medicinal materials which have no enough growth time or have been reserved for a long time. Through summarizing the styles and their common characteristics of the counterfeits and inferior drugs,it is helpful to raise vigilance and detect them. PMID- 22779356 TI - [Hypothesis and establishment of 2-dimensional molecular marking method inidentification of Chinese material medica]. AB - This paper introduced a new identification method, the 2-dimensional molecular marking method (2-DM), for Chinese materia medica identification. It can be used in genuine/false discriminating and quality evaluating for the Chinese materia medica. Concept, principle and process of 2-DM method were introduced in this paper. The technical advantages and contributions of 2-DM method in the study of Chinese materia medica were also discussed. Generally speaking, the occurring of 2-DM method would not only expand connotation of identification of Chinese materia medica but provide another effective way for quality evaluating. PMID- 22779357 TI - [Identification of Junci Medulla using DNA barcoding technique]. AB - OBJECTIVE: To identify Junci Medulla using the ITS2 barcode. METHOD: The ITS2 regions of Juncus effuses and its closely related species were PCR amplified and sequenced. Sequence assembly and consensus sequence generation were performed using the CodonCode Aligner. The Kimura 2-Parameter (K2P) distances were calculated using software MEGA 5.0. Identification analyses were performed using BLAST1, Nearest Distance, PWG Distance and neighbor-joining (NJ) methods. RESULT: The intra-specific genetic distances of J. effuses were ranged from 0 to 0.005, which were far lower than inter-specific genetic distances between J. effuses and its closely related species (0.215-0.614). All the four methods showed that ITS2 could discriminate J. effuses from its closely related species correctly. CONCLUSION: The ITS2 region is an efficient barcode for authentication of Junci Medulla, and our study further confirmed the ability of ITS2 to identify traditional Chinese medicinal materials. PMID- 22779358 TI - [Locality identification of Chinese medicinal plant Scutellaria baicalensis (Lamiaceae) population-level DNA barcoding]. AB - Scutellaria baicalensis is an important traditional Chinese medicine and Scutellaria flavonoids have received worldwide attention in recent years. It is the basis of controlling quality of S. baicalensis to develop a reliable genetic marker system used to identify locality of origin. Because of the characteristics of maternal inherited and high-rate of evolution, the cpDNA intergenic spacer can effectively elucidate the degree of genetic variation in different areas of the same species (populations), which can be used as the population-level DNA barcoding to locality identify. In this study, we have used the molecular phylogeography analysis for the three cpDNA intergenic spacers atpB-rbcL, trnL trnF and psbA-trnH of 17 wild populations from different localities, which reveals the 20 haplotypes, including 13 polymorphic sites and constitutes a shallow gene tree. The authers have divided the haplotypes of S. baicalensis into three grades of population-level DNA barcoding according to the frequence and geographic distribution: 3 highest-frequency haplotypes as area-population-level DNA barcoding, 3 haplotypes were mainly shared by 2-3 adjacent populations as region-population-level DNA barcoding, and there are also 8 unique-population haplotypes as unique-population-level DNA barcoding. The result of this study reveals that population-level DNA barcoding is a reliable genetic marker used to locality identify of S. baicalensis. PMID- 22779359 TI - [DNA bacording of Verbenaceae medicinal plant by using ITS2 and psbA-trnH region]. AB - OBJECTIVE: To evaluate the ability of several hotspot candidate sequence of DNA barcodes for identifying medicinal plant species in Verbenaceae. METHOD: Using universal primers, three chloroplast sequences, psbA-trnH, rbcL, matK, two nuclear ribosomal DNA ITS2 and ITS were amplified and sequenced. PCR amplification and sequencing efficiency, intra- and inter-specific variation, barcoding gap and identification efficiency (with BLAST 1 and Nearest Distance methods) were used to evaluate these loci. RESULT: The rate of successful amplification using matK was too low to further analyze, and the rate of successful amplification and sequencing using psbA-trnH, ITS, and ITS2 and rbcL sequence was 83.6%, 83.6%, 96.4%, 98.2%, respectively. The rate of successful identification using psbA-trnH, ITS, and ITS2 was 100% at the species level except that rbcL was 77.8%, 75.9% for 55 samples belonging to 32 species, but ITS2 did better in intra- and inter-specific variation, barcoding gap than the other loci. The rate of successful identification of ITS2 was 89.5%, 87.6% even when joining the date of 165 samples from GenBank. CONCLUSION: It proposes that the combination of ITS2 and psbA-trnH senquence is promising for the identification of the species in Verbenaceae. PMID- 22779360 TI - [Applying DNA barcoding technique to identify menthae haplocalycis herba]. AB - OBJECTIVE: To identify Menthae Haplocalycis Herba and its closely related species using DNA barcoding technique. METHOD: Total genomic DNA was isolated from Mentha canadensis and its closely related species. Nuclear DNA ITS2 sequences were amplified, and purified PCR products were sequenced. Sequence assembly and consensus sequence generation were performed using the CodonCode Aligner V3.0. The Kimura 2-Parameter (K2P) distances were calculated using software MEGA 5.0. Identification analyses were performed using BLAST1, Nearest Distance and neighbor-joining (NJ) methods. RESULT: The intra-specific genetic distances of M. canadensis were ranged from 0 to 0.006, which were lower than inter-specific genetic distances between M. canadensis and its closely related species (0.071 0.231). All the three methods showed that ITS2 could discriminate M. canadensis from its closely related species correctly. CONCLUSION: The ITS2 region is an efficient barcode for identification of Menthae Haplocalycis Herba, which provides a scientific basis for fast and accurate identification of the herb. PMID- 22779361 TI - [Using ITS2 barcode to identify ephedrae herba]. AB - OBJECTIVE: To identify Ephedrae Herba using the ITS2 barcode and to secure its quality and safety in medication. METHOD: Total genomic DNA was isolated from Ephedrae Herba and its closely related species. Nuclear DNA ITS2 sequences were amplified, and purified PCR products were sequenced. Sequence assembly and consensus sequence generation were performed using the CodonCode Aligner. The Kimura 2-Parameter (K2P) distances were calculated using software MEGA 5.0. Identification analyses were performed using BLAST1, Nearest Distance and neighbor-joining (NJ) methods. RESULT: The intra-specific genetic distances of Ephedrae Herba were ranged from 0 to 0.002. The inter-specific genetic distances between Ephedrae Herba and its closely related species were ranged from 0.004 to 0.034. All the three methods showed that ITS2 could discriminate Ephedrae Herba from its closely related species correctly. CONCLUSION: The ITS2 region is suitable to be used for authentication of Ephedrae Herba, and our study further confirmed the effectiveness of ITS2 to identify traditional Chinese medicinal materials. PMID- 22779362 TI - [Investigation on production process quality control of traditional Chinese medicine--Banlangen granule as an example]. AB - For the quality management system of herbal medicines, intermediate and finished products it exists the " short board" effect of methodologies. Based on the concept of process control, new strategies and new methods of the production process quality control had been established with the consideration of the actual production of traditional Chinese medicine an the characteristics of Chinese medicine. Taking Banlangen granule as a practice example, which was effective and widespread application, character identification, determination of index components, chemical fingerprint and biometrics technology were sequentially used respectively to assess the quality of Banlangen herbal medicines, intermediate (water extraction and alcohol precipitation) and finished product. With the transfer rate of chemical information and biological potency as indicators, the effectiveness and transmission of the above different assessments and control methods had been researched. And ultimately, the process quality control methods of Banlangen granule, which were based on chemical composition analysis-biometric analysis, had been set up. It can not only validly solute the current status that there were many manufacturers varying quality of Banlangen granule, but also ensure and enhance its clinical efficacy. Furthermore it provided a foundation for the construction of the quality control of traditional Chinese medicine production process. PMID- 22779363 TI - [Quick identification of sun-dried and sulfur-fumigated angelicae sinensis radix by Fourier transform infrared spectroscopy]. AB - OBJECTIVE: To develop a quick identification method for the sun-dried and sulfur fumigated Angelicae Sinensis Radix used by Fourier transform infrared spectroscopy (FTIR) combined with second derivative infrared spectroscopy. METHOD: The alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Angelicae Sinensis Radix were analyzed by using FTIR, the further analysis was used by second derivative infrared spectroscopy. RESULT: There existed differences between their infrared spectra either extracted by ethanol or water, while the distinctions were more obvious after analyzing their alcoholic and aqueous extracts through high resolution of second derivative infrared spectroscopy. Infrared spectra showed that the absorption peaks of Angelicae Sinensis Radix were significantly reduced and a new absorption peak appeared after sulfur-fumigated process in alcoholic extracts, while both of them changed markedly in the "fingerprint region" ranging from 1 000 to 400 cm(-1) in aqueous extracts. Second derivative spectra showed that the absorption peaks of sulfur fumigated Angelicae Sinensis Radix extracted by ethanol weakened and disappeared at about 3 578 cm(-1) and 3 541 cm(-1), while both of them differed significantly from each other ranging from 1 400 to 1 200 cm(-1) as well as 800 cm(-1) to 600 cm(-1), difference also existed between them extracted by water ranging from about 3 900 to 3 850 cm(-1) and 3 800 to 3 750 cm(-1). CONCLUSION: The FTIS method combined with second derivative can be utilized to distinguish sun-dried and sulfur-fumigated Angelicae Sinensis Radix efficiently, conveniently and accurately, and provide a basis for identification and quality control of Angelicae Sinensis Radix. PMID- 22779364 TI - [Correlation of lignans content and antioxidant activities of Schisandra chinensis fruits by using stoichiometry method]. AB - OBJECTIVE: To establish a quick method for evaluation of the antioxidant activities based on the correlation analysis of lignans content and antioxidant activities of Schisandra chinensis fruits. METHOD: The content of five lignans components in 37 batches of S. chinensis fruits from different regions of Jilin province were measured by HPLC. Simultaneously, the antioxidant activities of the above samples were detected, such as lipid peroxidation inhibition activity in liver (LPIL), kidney (LPIK) and brain (LPIB) and the clearance rate of DPPH (CRD). Bivariate correlation analysis and stepwise regression analysis were carried out by the software of SPSS for windows 11.5. RESULT: The results of bivariate correlation analysis showed that deoxyschizandrin was negative correlation (P<0.01) to the activity of LPIL, LPIB, CRD. Schisandrin was positive correlation (P<0.01) to the activity of LPIL, LPIB, CRD. Schisandrol B was also positive correlation (P<0.05 or P<0.01) to the above four kinds of antioxidant activity. The results of stepwise regression analysis were mostly consistent with the bivariate correlation analysis results. For the other 10 batches of samples, the simulated antioxidant activities according to the regression equation calculated was consistent with the measured activities. CONCLUSION: By using the bivariate correlation analysis and linear stepwise regression analysis, the bioactive components related to the antioxidant activity of S. chinensis fruits were found. Meanwhile, the antioxidant activity of samples will be inferred according to the content of Schisandra lignans. PMID- 22779365 TI - [Preliminary application of atomic force microscopy on identification of native habitat of Chinese medicine decoction pieces]. AB - Identification of the native habitat of Chinese medicine decoction pieces plays an important role in the use of Chinese Heber medicine. However, the traditional method always based on subjective description, lack of quantitative information. In this study, nanomechanical analysis of Ophiopogonis Radix, Polygonati Odorati Rhizoma and Curcumae Aromaticae Radix coming from different districts was carried out by using the force-distance curve of atomic force microscopy (AFM), including stiffness (represented by the slope of the force curve) and adhesion work (calculated via the adhesion area of the retrace line in force-distance curve). The results showed that the Ophiopogonis Radix from Sichuan province (slope 0.03 +/- 0.001) was significantly stiffer but less sticky [adhesion work 393.98 +/- 49.21 x 10(-10)) J] in comparison with that from Hubei province [slope 0.018 +/- 0.001, adhesion work (985.67 +/- 91.61) x 10(-10) J]; the Polygonati Odorati Rhizoma Hunan province was stiffer (slope 0.03 +/- 0.002) and stickier [adhesion work (413.67 +/- 92.58) x10(-10) J] than that from Dongbei province [slope 0.019 +/- 0.002, adhesion work (27.37 +/- 11.05) x 10(-10) J]; the Curcumae Aromaticae Radix from Sichuan province was also stiffer (slope 0.019 +/- 0.0017) but less stickier [adhesion work (1179.79 +/- 225.05) x 10(-10) J] than that from Hubei province [slope 0.013 +/- 0.0006, adhesion work (2831.27 +/- 93.71) x 10(-10)]. It is indicated that changes in mechanical properties of Chinese medicine decoction pieces correlate well with their origin. This method may provide quantitative information for the identification of the native habitat of Chinese medicine decoction pieces. PMID- 22779366 TI - [Rapid identification system for seedlings of medicinal Chrysanthemum morifolium]. AB - OBJECTIVE: To achieve the rapid identification for seedlings of medicinal Chrysanthemum morifolium, the discriminant equation was established and the software for rapid identification was designed. METHOD: Leaf structure of medicinal Chrysanthemum of 12 cultivars was analyzed to establish the discriminant equation based on variance analysis and discriminant analysis. On this basis, the identification program and software (based on the python language) were designed. RESULT: Through the analysis of variance and multiple comparisons for the 11 leaf parameter index data of 12 different cultivars, it was found that that the leaf parameters were significant different from each other and reached significant levels. The discriminant equation and the rapid identification software were set up based on the analysis of various indicators. CONCLUSION: The rapid identification system of seedlings of medicinal Chrysanthemum could be achieved through the establishment of discriminant equation combined with computer technology. PMID- 22779367 TI - [Comprehensive chemical pattern recognition of pantagirus semen]. AB - OBJECTIVE: To establish a method of comprehensive chemical pattern recognition of plantain seed via HPLC fingerprint, principal component analysis (PCA) and cluster analysis. METHOD: The chromatographic separation was performed on a C18 column (4.6 mm x 250 mm, 5 microm). The mobile phase was a mixture of acetonitrile-0.5% acetic acid aqueous solution in gradient elution. The HPLC fingerprint of ethyl acetate fraction of 24 batches Plantaginis Semen from different habits and varieties was set up and 10 common peaks were obtained. RESULT: The result of the principal component analysis (PCA) and cluster analysis is similar but there is disparity between them. CONCLUSION: The method could be used for the quality control and comprehensive evaluation of Plantaginis Semen. PMID- 22779368 TI - [Microscopic authentication method of traditional Chinese medicine Gusuibu]. AB - OBJECTIVE: To provide practical method for microscopic authentication of traditional Chinese medicine Gusuibu and its adulterants. METHOD: By means of light microscope, scanning electron microscopy and tissue section techniques, the morphology, the size of the rhizome scales and their bearing position in the original plants of Gusuibu and its adulterants, i. e. Drynaria roosii, D. delavayi, D. quercifolia and Pseudodrynaria coronans were analyzed. RESULT: There were significant differences between scales length of D. roosii, D. delavayi and P. coronans, while there was no significant difference between that of D. roosii and D. quercifolia. The scale teeth of D. delavayi were usually curved, bifid and uneven distributed at the scale fringe, which was different from that of the other three species. The base of the scales sinks in epidermis in D. roosii, D. quercifolia, and P. coronans, while it bore at the raised part of epidermis in D. delavayi. CONCLUSION: [corrected] Morphology, size and bearing position of the rhizome scales have significant differences in the several species. Therefore, these characteristics can be applied to the identification of Gusuibu and its adulterants. PMID- 22779369 TI - [Clustering analysis of karyotype resemblance-near coefficient for 6 Bupleurum species]. AB - OBJECTIVE: To explore the genetic evolutionary distance between plants by using karyotype parameters identification of medicinal plants. METHOD: The cluster analysis of karyotype resemblance-near coefficient and evolutionary distance was used for 6 Bupleurum species. RESULT: The results showed that there were the biggest karyotype resemblance-near coefficient (0.9920) and the smallest evolutionary distance (D(e) = 0.0080) between B. scorzonerifolium and B. chinense, indicating the closest relationship, and the minimum karyotype resemblance-near coefficient (0.4794) and the maximum evolutionary distance (D(e) = 0.7352) between B. smityii and B. falcatum, indicating the most distant relationship. CONCLUSION: Karyotype was an important parameter for identification of medicinal plants because karyotype was stabilized for species. The genetic distance between in 6 species of Bupleurum species was obtained by karyotype clustering analysis of karyotype resemblance-near coefficient. There was the bigger evolutionary distance between the species which had different chromosome number. PMID- 22779370 TI - [Micromorphological comparative identification between several Chinese herbal medicines and their counterfeits]. AB - OBJECTIVE: To identify comparatively several commercial Chinese herbal medicines and their counterfeits. METHOD: The micromorphological characters were identified. The shape, surface, section and other characters of the medicinal materials were identified by using anatomical lens and scanning apparatus. Pictures were taken and saved. RESULT: Main micromorphological differences between several Chinese herbal medicine including Lonicera macranthoides, L. similis, Cuminum cyminum, Plantago asiatica, Cuscuta chinensis, Sinapis alba, Salvia miltiorrhiza and their counterfeits were identified. CONCLUSION: The reference for the authenticity identification of Chinese herbal medicine and helpful experiences for the research of the same subject were provided. PMID- 22779371 TI - [Detection method and pattern recognition of ginseng and American ginseng pieces by electronic nose]. AB - OBJECTIVE: To distinguish the ginseng and American ginseng pieces accurately and rapidly by electronic nose technology and principal component analysis (PCA) method. METHOD: The optimum conditions of electronic nose for ginseng and American ginseng pieces, such as sample size and volume, headspace volume, incubation time and temperature were determined by the orthogonal test, the data were processed by the normalization method and the preprocessed data were analyzed PCA. RESULT: The detection methods of ginseng and American ginseng pieces was established by electronic nose, and the odor fingerprint figures of ginseng and American ginseng pieces were obtained, and ginseng and American ginseng pieces were distinguished by PCA recognition pattern. CONCLUSION: A new accurate and rapid method to distinguish ginseng and American ginseng pieces was established by electronic nose detection. PMID- 22779372 TI - The Health and Social Care Act (2012) in England. PMID- 22779373 TI - The platform for better oral health in Europe--report of a new initiative. AB - Public health practitioners are required to apply their competencies at a range of levels from governmental to small community groups. A recurring theme at BASCD conferences has been the need to influence policy at the highest level if improvements to oral health and better treatment of oral ill-health are to occur. This paper presents a clear example of such dental public health action at a European level. This report outlines the reasons why it is necessary to try to improve oral health within Europe, in general, and the European Union in particular. It goes on to describe how the newly formed Platform for Better Oral Health in Europe is trying to work at a macro level, and bring interested associations, groups and individuals together. Collectively they can then alert European institutions and national governments to oral health problems and promote policies to improve the current situation. It describes the current problems, their resource implications, the objectives of the Platform, its actions so far and its plans for the immediate future. It suggests that, if the problems are to be addressed, it will be necessary for all interested parties to work together at a European level to raise oral health issues higher on the E.U. agenda. PMID- 22779374 TI - Oral health in a life-course: birth-cohorts from 1929 to 2006 in Norway. AB - OBJECTIVES: The purpose of the work was to study the influence of the oral health environment at age 10, of adolescent and adulthood dental behaviours and of social status on oral health of three birth-cohorts in 1983 and two of the three birth-cohorts in 2006 in Norway. METHODS: The material comprised data from random samples of three birth-cohorts living in the counties of Sor- and Nord-Trondelag in 1983. The birth-cohorts were 1929-1938, 1939-1948 and 1959-1960. In 2006 two samples were drawn from the 1929-1938 and 1959-1960 birth-cohort. The data collection comprised standard clinical measurements and self-administered questionnaires. The early oral health environment and social status and gender were related to oral health in 1983 by multiple regressions. The impact of social status was studied in combined datafiles from 1983 and 2006. RESULTS: The oral health environment in childhood was important for adults' oral health. The attention from parents and the local environment lead to a better oral health outcome in adulthood. Social status affected choices leading to better oral health. Regular dental visits were important especially for the eldest birth cohort. Good oral health behaviours early and during adulthood were also important for oral health. Judged by number of tooth surfaces the difference between social status groups had not increased by 2006. CONCLUSIONS: A life course perspective provides an opportunity to understand oral health over time. The present study supports the assumption that oral health is continuously exposed to environmental and behavioural risks that lead to accumulated diseases in the dental tissues. PMID- 22779375 TI - Income-related inequalities in chewing ability of Europeans aged 50 and above. AB - OBJECTIVE: To describe income-related inequalities in chewing ability of the elderly populations residing in different European countries. BASIC RESEARCH DESIGN: This study investigates income-related inequalities on basis of cross sectional data from the Survey of Health, Ageing and Retirement in Europe (SHARE Wave 2). PARTICIPANTS: SHARE contains information on chewing abilities of 33,411 individuals aged 50+ from 14 different countries. MAIN OUTCOME MEASURES: Income related inequalities in chewing ability were identified by means of concentration indices (CI) and slope indices of inequality (SII). RESULTS: Disproportionate concentration of chewing ability among the rich elderly populations was evident for all countries except Ireland (relative inequality according to CI). Moreover, chewing abilities were significantly better amongst individuals from the highest income groups, compared with the lowest, for all countries except Italy, Switzerland, Czechia, Poland and Ireland (absolute inequality according to SII). Denture status explained some proportion of absolute but not of relative inequalities. CONCLUSION: There is considerable income-related inequality in chewing ability for several elderly populations residing in Europe. PMID- 22779376 TI - Effect of national recommendations on the sale of sweet products in the upper level of Finnish comprehensive schools. AB - INTERVENTIONS: In 2007, the Finnish National Board of Education (FNBE) and the National Public Health Institute (KTL) recommended to schools that they quit regular selling of candies and soft drinks. OBJECTIVE: The aim of this study was to determine how and why such selling changed from 2007 to 2008 after the national recommendation. METHODS: Surveys were conducted using online questionnaires to all upper comprehensive schools in Finland. In 2007, 480 (49%) and in 2008, 507 (51%) schools answered the questionnaire; 319 (32%) schools participated in both studies. Schools were asked whether they sold candies, soft drinks or other sweet products and, if theyhad changed the selling of these products, why. The changes in selling were analyzed by using McNemar's test. RESULTS: Of the responding schools, 56% (n=267) and 46% (n=233) sold sweet products in 2007 and 2008, respectively. Of the schools responding both years, 56% reported selling sweet products in 2007 and 50% in 2008. Selling had decreased by 11% among the schools that took part in both studies. The main reasons stated for quitting selling these products were concern about pupils' health (40%) and the recommendation of the FNBE and KTL (38%). CONCLUSIONS: The national recommendation was followed by some decrease in sale of sweet products. For further progress, new actions, both policy measures and broader public involvement, may be needed. PMID- 22779377 TI - A review of strategies to stimulate dental professionals to integrate smoking cessation interventions into primary care. AB - OBJECTIVE: To summarise evidence regarding the effectiveness of various implementation strategies to stimulate the delivery of smoking cessation advice and support during daily dental care. BASIC RESEARCH DESIGN: Search of online medical and psychological databases, correspondence with authors and checking of reference lists. Only studies were selected which examined a support strategy to promote tobacco use cessation having a component to be delivered by a dentist, dental hygienist or dental assistant in the daily practice setting. Furthermore only controlled studies and systematic reviews were included. Methodological quality and outcomes were independently summarised and checked by two reviewers. RESULTS: Eight studies met the inclusion criteria: 4 addressed strategies aimed at the dental professional and 4 addressed strategies aimed at both professional and patient. Only 4 of the studies were of a good quality. The 8 studies used combinations of implementation strategies, which made it difficult to evaluate the effectiveness of distinct components. Professional education appeared to enhance motivation for smoking cessation activities and advice giving. Organisational interventions (e.g., protocols, involvement of the whole team, referral possibilities) and incorporation of patient-oriented tools also contributed to the delivery of smoking cessation interventions. CONCLUSIONS: Multifaceted support strategies positively influence dental professionals' knowledge of smoking and smoking cessation, their motivation to give advice and their performance. As only 4 studies were of good methodological quality, it was not possible to draw firm conclusions about specific components. Additional research is needed to unravel which strategies best stimulate the provision of smoking cessation advice and support during daily dental practice. PMID- 22779378 TI - When can oral health education begin? Relative effectiveness of three oral health education strategies starting pre-partum. AB - OBJECTIVE: To test the impact of oral health education provided to pregnant mothers on subsequent practices within the infant's family. RESEARCH DESIGN: A quasi-experimental intervention trial comparing the effectiveness of 'usual care' to one, or both, of two oral health education resources: a 'sample bag' of information and oral health care products; and/or a nine-minute "Healthy Teeth for Life" video on postnatal oral health issues. PARTICIPANTS: Women attending the midwife clinic at approximately 30 weeks gestation were recruited (n=611) in a public hospital providing free maternity services. RESULTS AND CONCLUSIONS: Four months after the birth of their infant, relative to the usual care condition, each of the oral health education interventions had independent or combined positive impacts on mother's knowledge of oral health practices. However young, single, health care card-holder or unemployed mothers were less likely to apply healthy behaviours or to improve knowledge of healthy choices, as a result of these interventions. The video intervention provided the strongest and most consistent positive impact on mothers' general and infant oral health knowledge. While mothers indicated that the later stage of pregnancy was a good time to receive oral health education, many suggested that this should also be provided after birth at a time when teeth were a priority issue, such as when "baby teeth" start to erupt. PMID- 22779379 TI - Anterior tooth crowding and prevalence of dental caries in children in Szczecin, Poland. AB - OBJECTIVE: To test the effect of anterior tooth crowding on dental caries in Polish patients with primary, mixed and permanent dentition. BASIC RESEARCH DESIGN: Dental examinations based on WHO criteria and questionnaire surveys were performed on 225 children from Poland selected by stratified random sampling. The mean dmft/DMFT scores were recorded for primary, mixed and permanent dentition. Multivariate logistic regression was performed to identify associations between caries prevalence and other possible caries risk factors including crowding. RESULTS: The study population had high overall caries prevalence. Both caries prevalence and DMFT in anterior teeth of 15-19 year old adolescents with crowding were higher than in those without crowding. Multivariate analysis showed that the risk factors associated with anterior caries prevalence in patients aged 15-19 years were crowding (OR 3.71) and tooth brushing twice a day or less without interdental cleaning (OR 2.15). CONCLUSIONS: Tooth crowding may have been associated with anterior caries experienced in children aged 15-19 years and must be taken into consideration as a caries risk indicator. PMID- 22779380 TI - Clinical evaluation of three caries removal approaches in primary teeth: a randomised controlled trial. AB - OBJECTIVE: To evaluate the clinical performance and radiographic outcome of glass ionomer cement (GIC) restoration in primary molars using three caries removal techniques. BASIC RESEARCH DESIGN: Randomised clinical controlled trial. CLINICAL SETTING: Two standard dental clinics in 2 hospitals near Bangkok. PARTICIPANTS: A total of 276 children, aged 6-11, having dentinal caries on the occlusal and/or proximal surface extending at least one-third of dentine without signs and/or symptoms of irreversible pulpitis. INTERVENTION: Children were randomly allocated into 3 study groups with different caries removal techniques: Group 1, partial soft caries removal at enamel-dentine junction (EDJ) by spoon excavation; Group 2, complete soft caries removal by spoon excavation; and Group 3, conventional caries removal by steel burs. All cavity preparations were restored with GIC (Fuji IX, GC Corp., Japan). MAIN OUTCOME MEASURES: Clinical and radiographic evaluations were carried out at 6 and 12 months after restoration. RESULTS: After 12 months, 89, 89, and 88 restorations in Groups 1, 2 and 3 were evaluated. The cumulative survival rates of GIC restorations in Groups 1, 2 and 3 were 83%, 83%, and 89% while the cumulative survival rates of pulp were 99%, 100% and 98% respectively. There were no statistically significant differences in the survival of GIC restorations or pulp in the three groups (p > 0.05). CONCLUSION: The clinical and radiographic evaluations after 12 months indicated that partial soft caries removal at EDJ followed by GIC restoration was comparable to that of ART and conventional approaches. PMID- 22779381 TI - Relationship between gingivitis severity, caries experience and orthodontic anomalies in 13-15 year-old adolescents in Brno, Czech Republic. AB - OBJECTIVES: The aim of the present cross-sectional study was to assess oral health in adolescents selected from the ELSPAC (European Longitudinal Study of Pregnancy and Childhood) Bmo group and complete thus the ELSPAC series of studies on child general health. MATERIAL AND METHODS: Randomly selected children from the ELSPAC group (n=780) were examined clinically for dental and periodontal status, dental plaque, dental calculus and orthodontic anomalies. The following clinical parameters were assessed: DMFT score and its components, gingival index (GI), plaque index (PI) and calculus index (CSI). GI, PI and CSI were recorded on selected teeth. The presence/absence of orthodontic anomalies and their severity were recorded. ANOVA test for quantitative and XZ2 test for qualitative parameters evaluation were used. RESULTS: Mean DMFT of the group was 2.82 (SE 0.36), share of caries-free children 25.4%. Mean GI index of the cohort was 0.204 (SE 0.011), grade 0 was found in 36.9% children, grade 1 in 43.0%, and grade 2 in 19.5%. Statistical significant associations (p < 0.05) were observed in GI and DMFT, GI and DT value, GI and severity of orthodontic anomaly; significant difference was found in GI of caries-free and treated children vs. treatment need and in PI value between children with gingivitis vs healthy ones. CONCLUSION: The results demonstrated a relatively high caries experience, low level of gingival inflammation and relation between GI and DMFT, particularly in D component, and between GI and orthodontic anomalies. PMID- 22779382 TI - Prevalence of necrotizing ulcerative gingivitis and associated factors in Koranic boarding schools in Senegal. AB - BACKGROUND: Necrotizing ulcerative gingivitis is the most common clinical syndrome preceding noma. It is found in developing countries and in malnourished children and especially in deprived groups such as children at Koranic boarding schools. The objective of this study was to determine the prevalence of necrotizing ulcerative gingivitis and factors associated with its occurrence in a boarding school population. METHODS: This was a cross-sectional study of children in Koranic boarding schools in the city of Touba, Senegal. A multistage sampling strategy was used and 8 out of 17 schools were selected. The variables collected were gender, age, oral hygiene habits, duration of residence, presence of ulcerative gingivitis and plaque, and gingival bleeding index. A logistic regression analysis with R software using the manual procedure down was used to identify factors associated with the dependent variables. RESULTS: There were 501 participants and boys made up 92% of the study group. The mean age was 9.3 (sd 4.0) years. The mean of duration residence was 3.4 (sd 1.5) years. The prevalence of necrotizing ulcerative gingivitis was 37% and 81% of children did not use a toothbrush or a chewing-stick. The length of residence, school size, hygiene habits and plaque and bleeding indices were significantly associated with necrotizing gingivitis after adjustment for other variables. CONCLUSION: It is necessary to develop oral hygiene programs, to establish policies to manage the oral health of children and to improve health and nutrition at Koranic boarding schools. PMID- 22779383 TI - Compliance with school F-milk and non-F milk intake in 3 to 4 and 6 to 7-year-old children. AB - BACKGROUND: Fluoridated (F) milk schemes are employed in six countries to reduce dental caries in children. To maximise their benefits considerable uptake is required. Measuring compliance and understanding contributing factors is important in evaluating the effectiveness of schemes since it can be unclear whether reported sub-optimal fluoride (F) intakes, measured through urinary F excretion, are due to sub-optimal F contents of milks or lack of compliance with consumption. OBJECTIVES: To determine compliance with milk consumption for children receiving non-F or F milk (containing 0.5 or 0.9 mgF per 189 ml carton) and rationalise the use of compliance data for clinical observational or intervention studies involving F milk schemes. RESEARCH DESIGN: Partially randomised, partial cross-over study. PARTICIPANTS: 50 children aged 3-4 and 6-7y consuming non-F (n=50) and F milk (0.5 mgF; n=15 children; 0.9mg F; n=16 children) at school. RESULTS: Mean compliance for both non-F and F milk was > or =90% in each of the groups studied and showed no statistically significant difference for children using both milks. The 95% central range of proportions of milk consumed for groups of individuals was wider for 0.9mgF milk (25% to 100%) than for 0.5 mgF milk (81% to 100%) although the greatest range of variation in compliance for within individual observations was seen for non-F milk consumption and in older children. CONCLUSION: Assessment of compliance with consumption should be included when dental efficacy of F milk consumption is being investigated or evaluated to quantify F exposure from milk. This is important, particularly if a change in the F dose of F milk might be under consideration. PMID- 22779384 TI - Concerns of the wider public health community about the impact of the health & social care act on the NHS and it's implications for health improvement and inequalities. PMID- 22779385 TI - Breastfeeding past and present: a time for celebration and reflection. PMID- 22779386 TI - Political perspectives on integrated care. PMID- 22779387 TI - Breastfeeding: differing views. PMID- 22779388 TI - Breastfeeding: differing views. PMID- 22779389 TI - Helping homeless children achieve their potential. PMID- 22779390 TI - Establishing an antenatal group for families with a diagnosis of cleft lip. AB - U.K. cleft teams offer antenatal packages of care, which seek to be research based and respond locally to national standards of care set by the U.K. cleft nurse's special interest group (SIG). In April 2010 the 18-to-20-week National Health Service (NHS) Foetal Anomaly Ultrasound Scan Programme (FASP) standards and guidance for England were changed to include routine screening of the face to improve national pick up rates for cleft lip, which should increase referrals to cleft teams. This article aims to discuss the development of a specialist cleft antenatal group, established as a collaborative project between clinical nurse specialists (CNS) and clinical psychologists in the north-west England, Isle of Man and North Wales (NWNW) Cleft Network. Two pilot groups ran in 2008. Families referred to the team in the antenatal period were invited to attend a 'one-off' group before their child's birth. The group aim was to facilitate parental adjustment to cleft diagnosis in the antenatal period. Regular groups were then established in both network surgical hubs (Alder Hey and Royal Manchester Children's Hospitals (AHCH and RMCH)) every three or four months as part of the routine package of care provided by the team. Attendance at these groups ranged from 30-50% of those invited between 2008 to 2011. Feedback forms from attendees have informed the evolution of the group. The groups facilitate peer support at an important adjustment time for families. PMID- 22779391 TI - Students' experiences of a placement with health visitors during their adult nurse training. AB - This qualitative study explored the experiences of adult nursing students from one university who had undertaken a clinical placement with health visitors. A convenience sample of 10 students were recruited to the study and semistructured interviews used to gather data. Interviews were digitally recorded, transcribed verbatim and subject to thematic analysis. Three global themes emerged: the learning experience; mentors and mentorship; and the nursing and health visiting relationship. PMID- 22779392 TI - Befriending breastfeeding: a home-based antenatal pilot for south Asian families. AB - In the last decade recognition of the impact of social inequalities on health has resulted in a refocus of the public health agenda, with health visitors having a pivotal role. While this involvement is in the form of family-centred public health, it is also intended to involve work with the wider community and primarily focuses on beginning to address the injustice of inequality before a child is born, acknowledging that early intervention is key to breaking the cycle of deprivation. Such inequalities disproportionately affect those from black and minority ethnic (BME) groups who are more likely to report long-term ill health than their white counterparts. Access to healthcare services is restricted not only by family choices but also by difficulties of location and language. Numerous initiatives to address these issues have been implemented in the last 10 years, from Sure Start centres to maternity service reform, but the level of engagement from women from BME groups is not equal to their counterparts. In one locality in Oxford there is a high concentration of families from Pakistan and Bangladesh who, despite concerted efforts, have remained hard to reach. This project attempted to redesign the current antenatal breastfeeding information service, and aimed to produce evidence to guide practice to better connect with this group. The review considers evidence provided by the literature base and uses a home visiting approach to investigate the topic. Results are correlated and compared, and recommendations for the future are presented. PMID- 22779393 TI - Breastfeeding in Brighton and Hove: a success story. PMID- 22779394 TI - A 'hearts and minds' approach becoming 'baby friendly'. PMID- 22779395 TI - Mary Seacole Award: Improving the health and wellbeing of the Nepalese community in Hampshire. PMID- 22779396 TI - Recognising psoriasis in children. AB - Psoriasis is a chronic skin condition, which can affect children and young people at any age. This article will provide a basic overview of the condition and describe those types common to children. Treatments and general nursing management will be discussed. PMID- 22779397 TI - Improving breastfeeding outcomes: the impact of tongue-tie. AB - A tongue-tie (ankyloglossia) is defined as a lingual frenulum that is short, tight and restricts normal tongue movement. The tongue-tied newborn baby then has a mechanical difficulty attaching to his mum's breast and maintaining attachment to feed effectively. In the hands of skilled carers, this mechanical problem can be resolved by releasing the frenulum (frenulotomy) and the baby's access to his/her mother's breast milk be preserved. Published research on this subject has undergone justifiable criticism. Robust methodology was lacking in earlier studies. An overview of the course of researchers' response to critique is discussed. The care pathway in place in mid-Norfolk for mother and baby dyads where the baby's tongue-tie compromises efficient breastfeeding is outlined. PMID- 22779398 TI - The NHS in England: good place to work? PMID- 22779399 TI - On the verge of the 21st century there tends to be a panic in the struggle against communicable diseases. PMID- 22779400 TI - Thermochemical properties and bond dissociation energies of C3-C5 cycloalkyl hydroperoxides and peroxy radicals: cycloalkyl radical + (3)O2 reaction thermochemistry. AB - Cyclic aliphatic hydrocarbons are major components in modern fuels; they can be present in the reactants, and they can be formed during the gas-phase oxidation processes. In combustion and thermal oxidation processes, these cyclics will form radicals that react with (3)O(2) to form peroxy radicals. In this study, density functional theory and higher level ab initio calculations are used to calculate thermochemical properties and bond dissociation energies of 3-5-membered cycloalkanes, corresponding hydroperoxides, hydroperoxycycloalkyl radicals, and cycloalkyl radicals that occur in these reaction systems. Geometries, vibration frequencies, and thermochemical properties, DeltaH(f 298) degrees , are calculated with the B3LYP/6-31 g(d,p), B3LYP/6-31 g(2d,2p), composite CBS-QB3, and G3MP2B3 methods. Standard enthalpies of formation at 298 K are evaluated using isodesmic reaction schemes with several work reactions for each species. Group additivity contributions are developed, and application of group additivity with comparison to calculated values is illustrated. Entropy and heat capacities, S degrees (T) and C(p) degrees (T) (5 K <= T <= 5000), are determined using geometric parameters and frequencies from the B3LYP/6-31 g(d,p) calculations. PMID- 22779401 TI - Efficient microbubble- and ultrasound-mediated plasmid DNA delivery into a specific rat liver lobe via a targeted injection and acoustic exposure using a novel ultrasound system. AB - To develop efficient gene delivery in larger animals, based on a previous mouse study, we explored the luciferase reporter gene transfer in rats by establishing a novel unfocused ultrasound system with simultaneous targeted injection of a plasmid and microbubble mixture into a specific liver lobe through a portal vein branch. Luciferase expression was significantly enhanced over 0-30 vol % of the Definity microbubbles, with a plateau between 0.5 and 30 vol %. The increase of gene delivery efficiency also depended on the acoustic peak negative pressure, achieving over 100-fold enhancement at 2.5 MPa compared with plasmid only controls. Transient, modest liver damage following treatment was assessed by transaminase assays and histology, both of which correlated with gene expression induced by acoustic cavitation. In addition, pulse-train ultrasound exposures (i.e., with relatively long quiescent periods between groups of pulses to allow tissue refill with microbubbles) produced gene expression levels comparable to the standard US exposure but reduced the extent of liver damage. These results indicated that unfocused high intensity therapeutic ultrasound exposure with microbubbles is highly promising for safe and efficient gene delivery into the liver of rats or larger animals. PMID- 22779403 TI - Sequence hydropathy dominates membrane protein response to detergent solubilization. AB - The ability to predict from amino acid sequence how membrane protein structures will respond to detergent solubilization would significantly facilitate experimental characterization of these molecules. Here we have investigated and compared the response to solubilization by the "mild" n-dodecyl-beta-D-maltoside (DDM) and "harsh" sodium dodecyl sulfate (SDS) of wild-type and point mutant "hairpin" (helix-loop-helix) membrane proteins derived from the third and fourth TM segments of the human cystic fibrosis transmembrane conductance regulator (CFTR) and the intervening extracellular loop. Circular dichroism spectroscopy, size-exclusion chromatography, and pyrene fluorescence spectroscopy were used to evaluate the secondary structures, hairpin-detergent complex excluded volumes, and hairpin compactness of the detergent-solubilized sequences. Sequence hydrophobicity is found to be the dominant factor dictating membrane protein response to detergent solubilization by DDM and SDS, with hairpin secondary structure exquisitely sensitive to mutation when DDM is used for solubilization. DDM and SDS differ principally in their ability to promote approach of TM segment ends, although hairpin compactness remains sensitive to point mutations. Our overall findings suggest that protein-protein and protein-detergent interactions are determined concomitantly, with the net hydropathy of residues exposed to detergent dominating the observed properties of the solubilized protein. PMID- 22779402 TI - PleurX peritoneal catheter drainage system for vacuum-assisted drainage of treatment-resistant, recurrent malignant ascites: a NICE Medical Technology Guidance. AB - The PleurX peritoneal drainage catheter for drainage of malignant ascites in a community setting has been evaluated by the NICE Medical Technologies Evaluation Programme. This article outlines the evidence included in the Sponsor's submission, the independent critique by the External Assessment Centre (EAC) and the recommendations made by the Medical Technologies Advisory Committee (MTAC). In accordance with the scope issued by NICE, the intervention technology was the indwelling PleurX peritoneal catheter drainage system, the comparator was large volume paracentesis (LVP; inpatient or outpatient) and the population was patients with treatment-resistant, recurrent malignant ascites. Nine studies (ten papers) were identified with a total of 180 PleurX-treated patients; six were case series with more than four patients that, despite being low in the hierarchy of evidence, provided useful safety information. Technical success of the initial PleurX placement procedure was 100% across five studies which reported this outcome. One study reported equal complication rates between patients treated with indwelling PleurX catheters (40 patients and 40 catheters) and those receiving repeated LVPs (67 patients and 392 procedures), 7.5% (3/40; 95% CI 1.6, 20) and 7.5% (5/67; 95% CI 2.2, 15), respectively. All remaining studies were single-arm and reported complication rates of between 0% and 59%; this wide range was largely due to variation in the definition of complications and adverse events. Using validated tools, one case series reported improvements in several ascites-related symptoms after placement of the PleurX catheter; however, an overall quality-of-life improvement at 12 weeks was not demonstrated. Positive patient opinions relating to improved symptom control and convenience were reported in a qualitative study. Cost analysis demonstrated that PleurX offered savings to the NHS when compared with repeated LVPs performed in an inpatient setting. This saving of L679 per patient was driven primarily by reducing hospital bed days (year 2009-2010 values), but would require 23.5 additional community nurse visits. Advice from clinical experts was that additional home visits were overestimated as many patients would receive such visits regardless of whether a PleurX drain had been fitted. The model demonstrated that PleurX would be more expensive than LVP procedures performed in a setting where one or less hospital bed days were used (e.g. day case or outpatient). There was uncertainty surrounding the number of patients for whom insertion of a PleurX drain would be appropriate as well as the point in the care pathway at which such treatment should be administered. MTAC supported the case for adoption and considered that the available evidence showed PleurX was clinically effective, has low complication rates, can improve quality of life and is less costly than inpatient LVP. In Medical Technology Guidance 9 (MTG9), NICE recommended that PleurX peritoneal catheter drainage system be considered for use in patients with treatment-resistant, recurrent malignant ascites. PMID- 22779404 TI - Total synthesis and complete stereostructure of gambieric acid A. AB - Total synthesis of gambieric acid A, a potent antifungal polycyclic ether metabolite, has been accomplished for the first time, which firmly established the complete stereostructure of this natural product. PMID- 22779405 TI - Label-free microRNA profiling not biased by 3' end 2'-O-methylation. AB - Accurate quantification of miRNA expression level is essential to the study of its biology, and many cutting-edge technologies have been developed to accommodate this need. Yet most of them were designed primarily for the "regular" RNAs such as animal miRNAs and may overlook the fact that plant miRNAs and many other small noncoding RNAs are 2'-O-methylated at the 3' end nucleotide. According to our experimental data and previous reports, this structural variation is detrimental to the effectiveness of the commonly used enzymatic labeling methods, leading to strongly biased results (~24-fold difference). Herein, we demonstrate that our Stacking-Hybridized Universal Tag (SHUT) microarray assay is well suited for unbiased profiling of both normal and methylated small RNA species. The detected signals of small RNAs with 2'-hydroxyl and 2'-O-methyl 3' ends are highly consistent (no significant difference at alpha = 0.01 level). For specificity, the presented method edges over others by its unique ability to discriminate single-base difference at or near the 5' end. Notably, as compared to many delicate techniques, this enzyme-free and label-free approach requires much less reagent and manipulation, benefiting the SHUT-based applications with more efficient workflow and highly reproducible results. PMID- 22779407 TI - Restarted local search algorithms for continuous black box optimization. AB - Several local search algorithms for real-valued domains (axis parallel line search, Nelder-Mead simplex search, Rosenbrock's algorithm, quasi-Newton method, NEWUOA, and VXQR) are described and thoroughly compared in this article, embedding them in a multi-start method. Their comparison aims (1) to help the researchers from the evolutionary community to choose the right opponent for their algorithm (to choose an opponent that would constitute a hard-to-beat baseline algorithm), (2) to describe individual features of these algorithms and show how they influence the algorithm on different problems, and (3) to provide inspiration for the hybridization of evolutionary algorithms with these local optimizers. The recently proposed Comparing Continuous Optimizers (COCO) methodology was adopted as the basis for the comparison. The results show that in low dimensional spaces, the old method of Nelder and Mead is still the most successful among those compared, while in spaces of higher dimensions, it is better to choose an algorithm based on quadratic modeling, such as NEWUOA or a quasi-Newton method. PMID- 22779406 TI - Inhibition of intracellular antiviral defense mechanisms augments lentiviral transduction of human natural killer cells: implications for gene therapy. AB - Adoptive immunotherapy with genetically modified natural killer (NK) cells is a promising approach for cancer treatment. Yet, optimization of highly efficient and clinically applicable gene transfer protocols for NK cells still presents a challenge. In this study, we aimed at identifying conditions under which optimum lentiviral gene transfer to NK cells can be achieved. Our results demonstrate that stimulation of NK cells with interleukin (IL)-2 and IL-21 supports efficient transduction using a VSV-G pseudotyped lentiviral vector. Moreover, we have identified that inhibition of innate immune receptor signaling greatly enhances transduction efficiency. We were able to boost the efficiency of lentiviral genetic modification on average 3.8-fold using BX795, an inhibitor of the TBK1/IKKE complex acting downstream of RIG-I, MDA-5, and TLR3. We have also observed that the use of BX795 enhances lentiviral transduction efficiency in a number of human and mouse cell lines, indicating a broadly applicable, practical, and safe approach that has the potential of being applicable to various gene therapy protocols. PMID- 22779408 TI - Inhibition of Bacillus subtilis natural competence by a native, conjugative plasmid-encoded comK repressor protein. AB - Under certain growth conditions, Bacillus subtilis can develop natural competence, the state in which it is able to bind, adsorb and incorporate exogenous DNA. Development of competence is a bistable process and is subject to complex regulation. Rok is a repressor of the key transcriptional activator of competence genes, comK, and limits the size of the subpopulation that develops competence. Here we report the finding that the large conjugative B. subtilis plasmid pLS20 harbours a rok homologue rok(LS20). Although the deduced product of rok(LS20) is considerably shorter than the chromosomally encoded Rok protein, we show that ectopic expression of the plasmid-encoded Rok(LS20) leads to inhibition of competence by repressing comK, and that the effects of the plasmid and chromosomally encoded Rok proteins are additive. We also show that pLS20 inhibits competence in a rok(LS20) -dependent manner and that purified Rok(LS20) preferentially binds to the comK promoter. By analysing the available databases we identified several additional rok-like genes. These putative rok genes can be divided into two groups and we propose that rok(LS20) is the prototype of a newly identified subgroup of nine rok genes. Finally, we discuss the possible role of the plasmid-located rok and its relatedness with other rok genes. PMID- 22779409 TI - Characteristics of people with epilepsy who attend emergency departments: prospective study of metropolitan hospital attendees. AB - PURPOSE: One fifth of people with established epilepsy attend hospital emergency departments (EDs) and one half are admitted each year. These ED visits are not necessarily required, and unplanned hospitalizations are costly. Reducing avoidable ED visits and admissions is a target in most health services. The development of interventions is, however, challenging. Policymakers lack information about users' characteristics, factors associated with ED use, as well as quality of care. This study provides this information. METHODS: We prospectively recruited patients attending three London EDs for seizures. They completed questionnaires on service use and psychosocial state. KEY FINDINGS: Eighty-five patients were recruited. The mean age was 41; 53% were male. The average number of ED attendances in the prior year (mean 3.2; median 2) exceeded that of other ED users and those with most chronic conditions. ED use was not homogenous, with some patients attending frequently. Compared to the wider epilepsy population, ED attendees experienced more seizures, anxiety, had lower knowledge of epilepsy and its management and greater perceived epilepsy-related stigma. In the previous 12 months, most patients' epilepsy outpatient care was consistent with standard criteria for quality. In descending order, lower knowledge, higher perceived stigma, poorer self-medication management, and seizure frequency were associated with more emergency visits. SIGNIFICANCE: People with epilepsy presenting to EDs reattend frequently. Interventions aiming at reduced ED use by this population should address lower knowledge, stigma, suboptimal self-management, and frequent seizures reported by patients. PMID- 22779410 TI - Is the two-chosen-one (2c1) taxation implementation in Thailand valid to serve as a model for how 2c1 taxation really works? PMID- 22779411 TI - An alternative taxation method for low- to middle-income countries. PMID- 22779412 TI - Alcohol excise taxation in Thailand: more than a simple one. PMID- 22779413 TI - Evidence from a high-income country. PMID- 22779414 TI - Two-chosen-one taxation: examining its potential effectiveness to reduce drinking initiation and heavy alcohol consumption in low- to middle-income countries. PMID- 22779415 TI - Commentary on Peters et al. (2012): cannabis and tobacco policy correlates--why not try to reduce harm? PMID- 22779416 TI - Commentary on Larsen et al. (2012): throwing the baby out with the bathwater- teething problems with implicit attitude-behaviour links. PMID- 22779417 TI - Commentary on Michie et al. (2012): the lid is off the black box. PMID- 22779418 TI - Commentary on Friguls et al. (2012): illicit drugs and pregnancy--testing is not a substitute for good clinical rapport. PMID- 22779419 TI - Commentary on Cunningham et al. (2012): benefit to clients--outcome monitoring and knowledge translation. PMID- 22779420 TI - 100 years ago in addiction science. PMID- 22779421 TI - A comparison of the low-level laser versus low intensity pulsed ultrasound on new bone formed through distraction osteogenesis. AB - OBJECTIVE: To assess and compare the effects of low-intensity pulsed ultrasound stimulation (LIPUS) and low-level laser therapy (LLLT) on the bone mineral density (BMD) of bone formed through distraction osteogenesis (DO) using dual energy x-ray absorptiometry (DEXA). BACKGROUND DATA: LIPUS and LLLT are noninvasive supporting treatment concepts used for wound healing. LIPUS has been used to accelerate bone healing through the therapeutic effect arising from piezoelectric and angiogenetic effects on cell membranes. LLLT known as "photobiomodulation" is used in the treatment of soft and hard tissue injuries. METHODS: The study was conducted with 15 New Zealand rabbits randomly divided into three groups of 5 according to treatment, as follows: Group A: DO was performed with no further treatment; Group B: DO was performed followed by 30 mW/cm(2) LIPUS at 1 Mhz for 20 min/day during the distraction period; Group C: DO was performed followed by 25 mW/cm(2) LLLT at 650 nm for 10 min/day during the distraction period. DEXA was used to examine the treated areas prior to surgery and at 30 and 60 days postoperatively. RESULTS: In the control group, the mean BMD values at both 30 and 60 days postoperatively were below the baseline level, whereas they were above at the same time intervals in the LIPUS group. In the LLLT group, the mean BMD value at 30 days postoperatively was below the baseline level, whereas it was above the baseline level at 60 days postoperatively. CONCLUSIONS: LIPUS and LLLT applied during the distraction period accelerated the DO treatment. PMID- 22779422 TI - Regulating the communication of genetic risk information: the Italian legal approach to questions of confidentiality and disclosure. AB - Communication of genetic risk is a complex process in which the rights of the individual and those of relatives may conflict with regard to the information revealed by DNA testing. If patients who participate in clinical genetic testing refuse to share their genetic information with at-risk relatives, healthcare professionals need to reach a proper ethical balance between the right of individual patients regarding the confidentiality of their genetic test result and the right of families to be informed about their genetic risk. Rules and legislation in most countries generally protect the confidentiality of medical information but allow limited disclosure of genetic test results without the patient's consent in specific cases when certain conditions are met. The aim of this article is to draw attention to how Italian policymakers have attempted to balance protection of autonomy and confidentiality, and protection of health by means of a hybrid instrument. Furthermore, we show that some of the requirements of that instrument depart from the most widely recognized standards for non consensual disclosure of genetic risk information, while at the same time allowing an unusually high level of discretion to healthcare professionals involved in genetic counseling and testing. PMID- 22779423 TI - Systematized linear porokeratosis: concept of type 2 segmental manifestation implies an increased cancer risk. PMID- 22779425 TI - Fibrin glue with autogenic bone marrow mesenchymal stem cells for urethral injury repair in rabbit model. AB - AIM: Fibrin glue has been used for tissue adhesives and wound sealing. This study aimed to establish an approach to treat rabbit urethral injuries using fibrin glue and mesenchymal stem cells (MSCs). METHODS: Rabbit urethral injury was performed by excising the subcutaneous tissue from the ventral aspect of the penile urethra. Thirty-six New Zealand rabbits were divided into four groups: injured without treatment (control), glue treatment (glue), glue and MSCs treatment (glue + MSCs), and without injury (normal). Animals were sacrificed and the penises were excised for analysis after treatment for 10 days (n=4) and 30 days (n=5). RESULTS: The fibrin glue had a porous structure with cellular compatibility to MSCs. Two rabbits developed urethral fistulae in the control group, but none did in either the glue or the glue + MSCs groups at day 10 and 30. Hematoxylin and eosin staining showed that the distance between the skin and the epithelial layer at the ventral aspect of the penis increased in the glue and glue + MSCs groups compared to the control group at day 10 and 30. The density of blood vessels in the injured area increased in the glue and glue + MSCs groups compared to the control at day 10 and 30. The average thickness of the epithelial layer in the glue + MSCs group showed the same increasing trend among the three groups at day 10 and 30. The thickness and the area of the smooth muscle that surrounds the urethral mucosa at the operative region increased compared to the thickness in the control and glue groups at day 10 and 30. Pancytokeratins (AE1/AE3) staining showed weak signals in the urethral fistulae in the control group compared with the glue and glue + MSCs groups. The transplanted MSCs have differentiated into endothelial and smooth muscle cells, contributing to the formation of blood vessels and the recovery of urethral smooth muscle. CONCLUSIONS: MSCs combined with fibrin glue showed improved neovascularization and smooth muscle formation in repairing urethral injury, resulting in effective prevention of the development of urethral fistulae. Our data indicate that fibrin glue combined with MSCs may be a feasible approach for repairing urethral injury. PMID- 22779424 TI - Novel N-linked aminopiperidine inhibitors of bacterial topoisomerase type II with reduced pK(a): antibacterial agents with an improved safety profile. AB - Novel non-fluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. N-Linked amino piperidines, such as 7a, generally show potent antibacterial activity, including against quinolone-resistant isolates, but suffer from hERG inhibition (IC(50) = 44 MUM for 7a) and QT prolongation in vivo. We now disclose the finding that new analogues of 7a with reduced pK(a) due to substitution with an electron-withdrawing substituent in the piperidine moiety, such as R,S-7c, retained the Gram-positive activity of 7a but showed significantly less hERG inhibition (IC(50) = 233 MUM for R,S-7c). This compound exhibited moderate clearance in dog, promising efficacy against a MRSA strain in a mouse infection model, and an improved in vivo QT profile as measured in a guinea pig in vivo model. As a result of its promising activity, R,S-7c was advanced into phase I clinical studies. PMID- 22779426 TI - In vivo absorption study of ritodrine hydrochloride in the buccal administration to rats. AB - BACKGROUND: Although ritodrine (RD)-hydrochloride (HCl), named RD-HCl, is widely used in the treatment of premature labor by intravenous prolonged infusion or frequent oral dosing of tablets, those administrations often lower patients' quality of life (QOL) or cause undesirable side effects, such as tachycardia; therefore, in this study, the potential usefulness of buccal administration as a novel administration method was examined in vivo. METHOD: First, the HPLC method was assessed for the determination of plasma RD concentration. Then, after RD-HCl solution in saline was administered intravenously (1 mg/kg), intragastrically (10 mg/kg) or buccally (10 mg/kg) in rats, the plasma concentration-time profiles were investigated, and the absorption extent and rate compared. RESULTS: The present modified determination method by HPLC with fluorescence detection (Ex. 278 nm, Em. 306 nm) was suitable to analyze the plasma level at 8-200 ng/mL. Buccal administration gave the best plasma concentration-time profile for maintenance of an effective plasma level and fewer side effects. Absorption rates calculated by deconvolution also supported better sustained absorption in buccal dosing. CONCLUSION: Buccal application of RD-HCl was demonstrated to be a potentially useful dosing method in the treatment of premature labor with RD-HCl. PMID- 22779427 TI - Correlation between visual acuity and OCT-measured retinal nerve fiber layer thickness in a family with ADOA and an OPA1 mutation. AB - PURPOSE: To assess the association between retinal nerve fiber layer (RNFL) thickness and visual acuity in a family from Siracusa (Sicily) with autosomal dominant optic atrophy (ADOA) due to a heterozygous c.869G>A OPA1 mutation. METHODS: Affected family members underwent complete neuro-ophthalmological evaluation, including visual acuity testing, colour vision testing, tonometry, visual field testing, colour fundus photography, pattern visual-evoked potential (PVEP) testing, and pattern electroretinography (PERG). Patients and age-matched control subjects were scanned by spectral-domain optical coherence tomography (SD OCT) to assess circumpapillary RNFL thickness. RESULTS: All patients showed the characteristic optic disc pallor and central scotomas in the visual field. PVEP testing and PERG also showed alterations consistent with ADOA. The average circumpapillary RNFL thickness was thinner in ADOA patients than in control subjects (60.87 +/- 6.58um and 108.13 +/- 6.53um, respectively; p = 0.0001). The visual acuity in patients with ADOA correlated significantly with the circumpapillary average RNFL thickness (r = -0.845, p = 0.008). CONCLUSIONS: OCT measured peripapillary RNFL thickness is reduced in ADOA patients compared with healthy subjects and correlates significantly with visual acuity in patients with ADOA. The photoreceptor layers are morphologically unaffected. PMID- 22779428 TI - Polymorphisms of tumor necrosis factor gene in primary myelofibrosis. PMID- 22779429 TI - Capreomycin susceptibility is increased by TlyA-directed 2'-O-methylation on both ribosomal subunits. AB - The binding site of the cyclic peptide antibiotics capreomycin and viomycin is located on the ribosomal subunit interface close to nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA. In Mycobacterium tuberculosis, the 2'-hydroxyls of both nucleotides are methylated by the enzyme TlyA. Loss of these methylations through inactivation of TlyA confers resistance to capreomycin and viomycin. We report here that TlyA orthologues occur in diverse bacteria and fall into two distinct groups. One group, now termed TlyA(I) , has shorter N- and C-termini and methylates only C1920; the second group (now TlyA(II) ) includes the mycobacterial enzyme, and these longer orthologues methylate at both C1409 and C1920. Ribosomal subunits are the preferred substrates for both groups of orthologues. Amino acid substitutions at the N-terminus of TlyA(II) reduce its ability to methylate these substrates. Growing pairs of recombinant TlyA(II) Escherichia coli strains in competition shows that even subtle changes in the level of rRNA methylation lead to significant differences in susceptibility to sub-inhibitory concentrations of capreomycin. The findings reveal that 2'-O methyls at both C1409 and C1920 play a role in facilitating the inhibitory effects of capreomycin and viomycin on the bacterial ribosome. PMID- 22779430 TI - High prevalence of silent brain infarction in patients presenting with mechanical heart valve thrombosis. AB - BACKGROUND: Symptomatic thromboembolic events including stroke occur frequently in patients with mechanical heart valves, particularly among those who are poorly anticoagulated. OBJECTIVE: This study set out to determine the prevalence of silent brain infarction (SBI) in this population. METHODS: This was a post hoc analysis of data from a randomized controlled trial carried out in a tertiary care academic medical center. The trial included participants from a randomized controlled trial of fibrinolytic therapy (FT) in patients with left-sided prosthetic valve thrombosis (PVT), who had undergone pre-treatment computed tomography (CT) scans of the brain. The prevalence of SBI in this population was investigated. MAIN OUTCOME MEASURE: Prevalence of silent brain infarction. RESULTS: Silent brain infarction was present in 27 of 72 patients (37.5%; 95% confidence interval [CI] 27.2, 49.1). Most patients with SBI (57; 82.6%) had sub therapeutic anticoagulation at presentation. We identified baseline characteristics that were associated with the presence of SBI using a logistic regression model. Atrial fibrillation (AF) was strongly associated with the presence of SBI (odds ratio [OR] 5.60; 95% CI 1.32, 23.87; p = 0.02). CONCLUSION: The high prevalence of SBI among this cohort of young patients with mechanical heart valves is alarming and calls for urgent efforts to improve the quality of anticoagulation. CLINICAL TRIAL REGISTRATION: Registered in the US National Institutes of Health registry at http://clinicaltrials.gov as NCT00232622. PMID- 22779433 TI - Amputations of upper and lower extremities, active and reserve components, U.S. Armed Forces, 2000-2011. AB - Traumatic amputations of limbs profoundly alter the lives of affected service members. Service members are at risk for traumatic amputations of limbs during combat deployments as well as from other hazards such as motor vehicle accidents. From 2000 to 2011, there were 6,144 incident cases of traumatic amputations among 5,694 service members. Over one-third of these service members (n=2,037) had major amputations (i.e., loss of a hand or foot or more). Male, junior enlisted members of the Army and Marine Corps in combat-specific military occupations have been most affected by major amputations. Nearly two-thirds of major amputations occurred during a deployment or were deployment-related. Recent increases in numbers of major amputations generally reflect the extent and intensity of ground combat operations in Iraq and Afghanistan. PMID- 22779431 TI - Multiple target-specific molecular imaging agents detect liver cancer in a preclinical model. AB - Liver cancer is the fifth most common cause of cancer deaths worldwide. Noninvasive diagnosis is difficult and the disease heterogeneity reduces the accuracy of pathological assays. Improvement in diagnostic imaging of specific molecular disease markers has provided hope for accurate and early noninvasive detection of liver cancer. However, all current imaging technologies, including ultrasonography, computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging, are not specific targets for detection of liver cancer. The aim of this study was to test the feasibility of injecting a cocktail of specific molecular imaging agents to noninvasively image liver cancer. The target-specific cocktail contained agents for imaging the neovasculature (RGD peptide), matrix metalloproteinase (MMP), and glucose transport ((18)F fluorodeoxyglucose [(18)F-FDG]). Imaging studies were performed in liver cancer cells and xenograft models. The distribution of MMP at the intracellular level was imaged by confocal microscopy. RGD, MMP, and (18)F-FDG were imaged on tumor bearing mice using PET, CT, X-ray, and multi-wavelength optical imaging modalities. Image data demonstrated that each agent bound to a specific disease target component. The same liver cancer xenograft contained multiple disease markers. Those disease markers were heterogenetically distributed in the same tumor nodule. The molecular imaging agents had different distributions in the whole body and inside the tumor nodule. All target-specific agents yielded high tumor-to-background ratios after injection. In conclusion, target-specific molecular imaging agents can be used to study liver cancer in vitro and in vivo. Noninvasive multimodal/multi-target-specific molecular imaging agents could provide tools to simultaneously study multiple liver cancer components. PMID- 22779432 TI - Ceftaroline fosamil in the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. AB - Ceftaroline fosamil is a cephalosporin antibacterial approved by the US Food and Drug Administration (FDA) for use in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). After intravenous administration, ceftaroline fosamil is rapidly converted to its bioactive metabolite, ceftaroline. Ceftaroline has broad spectrum in vitro activity against Gram-positive and Gram-negative bacteria, including contemporary resistant Gram-positive phenotypes, such as methicillin resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae. Because of its unique spectrum of activity, the Clinical and Laboratory Standards Institute (CLSI) designated ceftaroline as a member of a new subclass of beta-lactam antimicrobials, cephalosporins with anti-MRSA activity. The activity of ceftaroline against S. aureus extends to heteroresistant vancomycin-intermediate, vancomycin-intermediate, vancomycin-resistant and daptomycin-nonsusceptible isolates. Ceftaroline has low minimum inhibitory concentrations (MICs) for all tested species of streptococci, and has potent activity against S. pneumoniae isolates with varying degrees of penicillin resistance. The activity of ceftaroline is limited against Enterococcus faecalis and Enterococcus faecium and against anaerobes such as Bacteroides fragilis. The in vitro activity of ceftaroline includes many Gram-negative pathogens, but does not extend to bacteria that produce extended-spectrum beta-lactamases, class B metallo-beta-lactamases or AmpC cephalosporinases, or to most nonfermentative Gram-negative bacilli. Ceftaroline fosamil has been studied for the treatment of complicated skin and skin structure infections (cSSSI) and community-acquired pneumonia (CAP) in phase III randomized, double-blind, international, multicentre noninferiority clinical trials. Two identical trials (CANVAS 1 and CANVAS 2) compared the efficacy of ceftaroline fosamil with that of vancomycin plus aztreonam in 1378 adults with cSSSI. Results demonstrated that ceftaroline was noninferior to vancomycin plus aztreonam, with 91.6% in the ceftaroline fosamil group (pooled analysis) achieving clinical response compared with 92.7% in the vancomycin plus aztreonam group (difference -1.1%, 95% CI -4.2, 2.0). An additional analysis evaluated clinical cure in a subgroup of patients who met the FDA guidance definition of ABSSSI at treatment day 3. Clinical response, defined as cessation of lesion spread and absence of fever, was 74.0% in the ceftaroline fosamil group compared with 66.2% in the vancomycin plus aztreonam group (treatment difference 7.8%, 95% CI 1.3, 14.0). Clinical efficacy of ceftaroline fosamil in 1240 hospitalized adults with CAP was compared with that of ceftriaxone in two additional phase III trials (FOCUS 1 and FOCUS 2). Of note, because ceftriaxone does not have activity against MRSA, patients with confirmed or suspected MRSA CAP were excluded from the FOCUS trials. Results demonstrated that ceftaroline was noninferior to ceftriaxone, with 84.3% in the ceftaroline fosamil group achieving clinical cure compared with 77.7% in the ceftriaxone group (difference 6.7%, 95% CI 1.6, 11.8). An additional analysis of the trials was conducted in patients with moderate to severe CAP and at least one proven typical bacterial pathogen at baseline (i.e. CABP). Day 4 clinical response rates were 69.5% for ceftaroline and 59.4% for ceftriaxone (difference 10.1%, 95% CI 0.6, 20.6). In the phase III trials, adverse event rates were similar between groups. Overall, ceftaroline is well tolerated, which is consistent with the good safety and tolerability profile of the cephalosporin class. In summary, ceftaroline fosamil is a broad-spectrum parenteral cephalosporin with excellent in vitro activity against resistant Gram-positive pathogens, including MRSA, as well as many common Gram-negative organisms. It is a welcome treatment option for ABSSSI and CABP. PMID- 22779434 TI - Deaths by suicide while on active duty, active and reserve components, U.S. Armed Forces, 1998-2011. AB - Since 2010, suicide has been the second leading cause of death among U.S service members, exceeded only by war injury. Suicide mortality rates in the Army and Marine Corps have increased during the conflicts in Iraq and Afghanistan; however, most active duty service members who die by suicide have never deployed. During 1998-2011, 2,990 service members died by suicide while on active duty. Numbers and rates of suicide were highest among service members who were male, in the Army, in their 20s and of white race/ethnicity. Suicide death rates were 24 percent higher among divorced/separated than single, never-married service members. Firearms were the most frequently used method of suicide among both males and females. Numbers and rates of suicide among military members have increased sharply since 2005 and an increasing proportion of these suicides were by firearms. When adjusted for age, rates of suicide are somewhat lower among active military members than civilians. There are not well established and clearly effective interventions to prevent suicides--in general or specifically in a military population during wartime. PMID- 22779435 TI - Mental disorders and mental health problems, active component, U.S. Armed Forces, 2000-2011. AB - Mental disorders account for significant morbidity, health care utilization, disability, and attrition from military service; the health care burden associated with mental disorders has increased over the last several years. During the years 2000 through 2011, 936,283 active component service members were diagnosed with at least one mental disorder. Annual counts and rates of incident diagnoses of mental disorders have increased by approximately 65 percent over the last twelve years; this overall increase is largely attributable to diagnoses of adjustment disorders, depressive and anxiety disorders, and post-traumatic stress disorder. Rates of incident mental disorder diagnoses were higher in females than males and in service members under 30 years of age. These findings reinforce previous reports that have documented a rise in demand for mental health services in the active component force and suggest that continued focus on detection and treatment for mental health issues is warranted. PMID- 22779436 TI - Incident diagnoses of cancers and cancer-related deaths, active component, U.S. Armed Forces, 2000-2011. AB - In the United States, cancer is one of the five leading causes of death in all age groups among both men and women; overall, approximately one in four deaths is attributable to cancer. Compared to the general U.S. population, military members have been estimated to have lower incidence rates of several cancers including colorectal, lung, and cervical cancers and higher rates of prostate, breast, and thyroid cancer. Between 2000 and 2011 in active component members of the U.S. military, crude incidence rates of most cancer diagnoses have remained stable. 9,368 active component service members were diagnosed with one of the cancers of interest and no specific increasing or decreasing trends were observed. Cancer is an uncommon cause of death among service members on active duty and accounted for a total of 1,185 deaths during the 12-year surveillance period. PMID- 22779437 TI - Genetic improvement of biofuel plants: recent progress and patents. AB - Due to depleting reserves of fossil fuels, political uncertainties, increase in demand of energy needs and growing concerns of environmental effects, bioenergy as an alternative source of energy needs had taken centre stage globally. In this report, we review the progress made in lignocellulose, cellulose and fermentation based biofuels in addition to tree borne oil seeds. Algae as a source of feedstock for the biofuel has also been reviewed. Recent efforts in genome sequencing of biofuel crops and molecular breeding approaches have increased our understanding towards crop improvement of major feedstocks. Besides, patenting trends in bioenergy sector were assessed by patent landscape analysis. The results showed an increasing trend in published patents during the last decade which is maximum during 2011. A conceptual framework of "transgenesis in biofuels to industrial application" was developed based on the patent analytics viz., International Patent Classification (IPC) analysis and Theme Maps. A detailed claim analysis based on the conceptual framework assessed the patenting trends that provided an exhaustive dimension of the technology. The study emphasizes the current thrust in bioenergy sector by various public and private institutions to expedite the process of biofuel production. PMID- 22779438 TI - Development of energy plants and their potential to withstand various extreme environments. AB - Biomass utilization is increasingly considered as a practical way for sustainable energy supply and long-term environment care around the world. In concerns with food security, starch or sugar-based bioethanol and edible-oilderived biodiesel are severely restricted for large scale production. Alternatively, conversion of lignocellulosic residues from food crops could be considered, but due to its recalcitrance, the current biomass process is unacceptably expensive. In this context, genetic breeding of energy crops appears as a promising solution. To fulfil the global world need as both food and biofuel sources, energy crops are expected to be produced with higher yields and especially in marginal lands. This review focus on recent progress and patents dealing with energy plants and the challenges associated with bioenergy development. We also discuss the potential use of molecular approaches including genome sequencing, molecular markers, and genetic transformation for improving specific traits or generating new cultivars of energy plants. PMID- 22779439 TI - Genetic improvement of plants for enhanced bio-ethanol production. AB - The present world energy situation urgently requires exploring and developing alternate, sustainable sources for fuel. Biofuels have proven to be an effective energy source but more needs to be produced to meet energy goals. Whereas first generation biofuels derived from mainly corn and sugarcane continue to be used and produced, the contentious debate between "feedstock versus foodstock" continues. The need for sources that can be grown under different environmental conditions has led to exploring newer sources. Lignocellulosic biomass is an attractive source for production of biofuel, but pretreatment costs to remove lignin are high and the process is time consuming. Genetically modified plants that have increased sugar or starch content, modified lignin content, or produce cellulose degrading enzymes are some options that are being explored and tested. This review focuses on current research on increasing production of biofuels by genetic engineering of plants to have desirable characteristics. Recent patents that have been filed in this area are also discussed. PMID- 22779440 TI - Recent patents on genetic modification of plants and microbes for biomass conversion to biofuels. AB - Development of sustainable energy systems based on renewable biomass feedstocks is now a global effort. Lignocellulosic biomass contains polymers of cellulose, hemicellulose, and lignin, bound together in a complex structure. Liquid biofuels, such as ethanol, can be made from biomass via fermentation of sugars derived from the cellulose and hemicellulose within lignocellulosic materials, but pre-treatment of the biomass to release sugars for microbial conversion is a significant barrier to commercial success of lignocellulosic biofuel production. Strategies to reduce the energy and cost inputs required for biomass pre treatment include genetic modification of plant materials to reduce lignin content. Significant efforts are also underway to create recombinant microorganisms capable of converting sugars derived from lignocellulosic biomass to a variety of biofuels. An alternative strategy to reduce the costs of cellulosic biofuel production is the use of cellulolytic microorganisms capable of direct microbial conversion of ligno-cellulosic biomass to fuels. This paper reviews recent patents on genetic modification of plants and microbes for biomass conversion to biofuels. PMID- 22779442 TI - Energy landscapes of atomic clusters as black box optimization benchmarks. AB - We present the energy minimization of atomic clusters as a promising problem class for continuous black box optimization benchmarks. Finding the arrangement of atoms that minimizes a given potential energy is a specific instance of the more general class of geometry optimization or packing problems, which are generally NP-complete. Atomic clusters are a well-studied subject in physics and chemistry. From the large set of available cluster optimization problems, we propose two specific instances: Cohn-Kumar clusters and Lennard-Jones clusters. The potential energies of these clusters are governed by distance-dependent pairwise interaction potentials. The resulting collection of landscapes is composed of smooth and rugged single-funnel topologies, as well as tunable double funnel topologies. In addition, all problems possess a feature that is not covered by the synthetic functions in current black box optimization test suites: isospectral symmetry. This property implies that any atomic arrangement is uniquely defined by the pairwise distance spectrum, rather than the absolute atomic positions. We hence suggest that the presented problem instances should be included in black box optimization benchmark suites. PMID- 22779441 TI - Electrophysiological effects of single point transcutaneous 650 and 808 nm laser irradiation of rat sciatic nerve: a study of relevance for low-level laser therapy and laser acupuncture. AB - OBJECTIVE: The purpose of this study was to evaluate effects of transcutaneous 650 and 808 nm laser irradiation (LI) to a single point overlying rat sciatic nerve; a comparison to four point LI and relevance to the clinical application of low-level laser therapy (LLLT) and laser acupuncture (LA). BACKGROUND DATA: Transcutaneous LI inhibits somatosensory and motor conduction when delivered to four points overlying sciatic nerve; however, effects of the same total energy delivered to a single point over the nerve, equating to laser acupuncture, are undefined. METHODS: Transcutaneous 808 nm, 450 mW, (13.5 or 54 J) continuous wave (cw) mode or 650 nm, 35 mW, (1.1 or 4.4 J), cw LI or sham LI, was applied for 30 or 120 sec to a single point overlying the midpoint of rat sciatic nerve. Somatosensory evoked potentials (SSEPs) and compound muscle action potentials (CMAPs) were then recorded after 10 and 20 min, and after 24 and 48 h. RESULTS: 120 sec of 808 nm LI increased SSEP amplitudes only at 10 min, with no effect of 30 or 120 sec at other time points on SSEPs or on CMAPs. LI 650 nm for 30 or 120 sec did not alter SSEPs or CMAPs at any time point. CONCLUSIONS: Localized transcutaneous 808 LI to a single point overlying sciatic nerve increases SSEP amplitudes when compared with delivery of the same total energy to four points, which causes decreased SSEP amplitudes and conduction block. Therefore, the area and duration of delivery are important, independent variables with implications for clinical delivery of both LLLT and LA. PMID- 22779443 TI - Assessing the prosthetic needs of farmers and ranchers with amputations. AB - PURPOSE: Farmers and ranchers experience disabling injuries each year of which amputations account for 11%. Anecdotal evidence suggests that current prostheses may not be meeting the needs of farmers and ranchers with amputations. To better understand those prosthetic needs, a descriptive qualitative study was used to gather data with an engineering perspective. METHOD: Farmers with an upper- or lower-limb amputation were interviewed. Issues explored included current and past prostheses used, prosthetic failures, and ability to complete farm tasks using a prosthesis. Prosthetists providing services to this population were also interviewed to gain knowledge of specific devices and practises used in their geographic region. RESULTS: Interviews with 40 farmers and 26 prosthetists revealed several common themes related to prostheses including durability/utility, environment, adaptation, cost, and education. Farmers and ranchers with amputations often made modifications to their prostheses, farm equipment, and daily routines in order to return to their vocation. CONCLUSIONS: Farmers and ranchers with amputations have distinct prosthetic needs. Their return to farming can be facilitated by creating more durable, affordable, and adaptable prosthetic components. Our results can help guide design of more comprehensive surveys for further information gathering and new devices and establish best prosthetic practises for farmers and those in other physically demanding professions. PMID- 22779444 TI - Synthesis, characterization and in vitro studies of pegylated melphalan conjugates. AB - Melphalan, a drug used for the treatment of breast, ovaries and a certain type of cancer in the bone marrow, was conjugated to linear methoxy poly (ethylene glycol) (M-PEG) of 2000 and 5000, Da. An ester linkage between polymer and drug was used in the coupling to yield a polymeric prodrug. Purified esters were characterized by Maldi-Tof and IR spectroscopy methods. The modification allowed overcoming the known melphalan aqueous solubility problem (0.1 ug/ml) leading us to obtain a polymer-drug bioconjugate more suitable for oral and parental administration. It was found that molecular weight of M-PEG is critical for the conjugates stability, aqueous solubility (80 times and 123 times higher aqueous solubility for M-PEG 2000 and M-PEG 5000, respectively), and hemolytic activity. The melphalan caused 100% hemolysis above the concentration 3.5 ug/ml in 1 h. whereas conjugate of M-PEG 2000 and M-PEG 5000 shows 81.3 +/- 0.5% and 48.8 +/- 1.5% hemolysis, respectively at 32 ug/ml after1 h. Further In vitro anticancer activity of melphalan and its conjugates was performed with breast cancer MCF-7 cell lines. It shows that LD50 concentration was higher 1.14 and 2 um for M-PEG 2000 and M-PEG 5000, respectively in comparison to pure melphalan (0.74 um). Above studies revealed improved pharmacokinetics properties upon conjugation. PMID- 22779445 TI - Mechanistic insights into PEPT1-mediated transport of a novel antiepileptic, NP 647. AB - The present study, in general, is aimed to uncover the properties of the transport mechanism or mechanisms responsible for the uptake of NP-647 into Caco 2 cells and, in particular, to understand whether it is a substrate for the intestinal oligopeptide transporter, PEPT1 (SLC15A1). NP-647 showed a carrier mediated, saturable transport with Michaelis-Menten parameters K(m) = 1.2 mM and V(max) = 2.2 MUM/min. The effect of pH, sodium ion (Na(+)), glycylsarcosine and amoxicillin (substrates of PEPT1), and sodium azide (Na(+)/K(+)-ATPase inhibitor) on the flux rate of NP-647 was determined. Molecular docking and molecular dynamics simulation studies were carried out to investigate molecular interactions of NP-647 with transporter using homology model of human PEPT1. The permeability coefficient (P(appCaco-2)) of NP-647 (32.5 * 10(-6) cm/s) was found to be four times higher than that of TRH. Results indicate that NP-647 is transported into Caco-2 cells by means of a carrier-mediated, proton-dependent mechanism that is inhibited by Gly-Sar and amoxicillin. In turn, NP-647 also inhibits the uptake of Gly-Sar into Caco-2 cells and, together, this evidence suggests that PEPT1 is involved in the process. Docking and molecular dynamics simulation studies indicate high affinity of NP-647 toward PEPT1 binding site as compared to TRH. High permeability of NP-647 over TRH is attributed to its increased hydrophobicity which increases its affinity toward PEPT1 by interacting with the hydrophobic pocket of the transporter through hydrophobic forces. PMID- 22779447 TI - Objective assessment of the severity of unilateral facial palsy using OKAO Vision(r) facial image analysis software. AB - CONCLUSION: Severity of ipsilateral facial palsy (UFP) can be assessed objectively by use of OKAO Vision(r). Facial symmetry percentage (FSP) values were well correlated with the results by two conventional grading systems. OBJECTIVES: To introduce the basic principle of facial motion analysis using OKAO Vision(r), to represent the data measured in patients with UFP, and to show the correlation between the severity of facial palsy assessed by this method and conventional systems. METHODS: Two independent facial motions, closing the eyes and grinning, were recorded with a video camera. By comparing the movement distances between right and left sides, the eye symmetry ratio (ESR) and grin symmetry ratio (GSR) were obtained. The degree of UFP was assessed by FSP, which was calculated by the formula: FSP = (ESR + GSR)/2 * 100 (%). FSP was measured in 12 normal volunteers and in 30 patients with UFP. RESULTS: In patients with UFP, varying degrees of FSP were noted corresponding to the grade of facial palsy. The severity of facial palsy assessed by FSP was closely correlated with the Yanagihara score (r = 0.88, p < 0.05) and was inversely related to the House Brackmann grade (r = -0.90, p < 0.05). PMID- 22779446 TI - Stromal cell-derived factor-1beta potentiates bone morphogenetic protein-2 stimulated osteoinduction of genetically engineered bone marrow-derived mesenchymal stem cells in vitro. AB - Skeletal injuries are among the most prevalent clinical problems and bone marrow derived mesenchymal stem/stromal cells (BMSCs) have successfully been used for the treatment thereof. Stromal cell-derived factor-1 (SDF-1; CXCL12) is a member of the CXC chemokine family with multiple splice variants. The two most abundant variants, SDF-1alpha and SDF-1beta, share identical amino acid sequences, except for four additional amino acids at the C-terminus of SDF-1beta, which may mediate surface stabilization via glycosaminoglycans and protect SDF-1beta from proteolytic cleavage, rendering it twice as potent as SDF-1alpha. Increasing evidence suggests that SDF-1 is involved in bone formation through regulation of recruitment, engraftment, proliferation, and differentiation of stem/progenitor cells. The underlying molecular mechanisms, however, have not yet been fully elucidated. In this study, we tested the hypothesis that SDF-1beta can potentiate bone morphogenetic protein-2 (BMP-2)-stimulated osteogenic differentiation and chemotaxis of BMSCs in vitro. Utilizing retrovirus-mediated gene transfer to generate novel Tet-Off-SDF-1beta BMSCs, we found that conditional SDF-1beta expression is tightly regulated by doxycycline in a dose-dependent and temporal fashion, leading to significantly increased SDF-1beta mRNA and protein levels. In addition, SDF-1beta was found to enhance BMP-2-stimulated mineralization, mRNA and protein expression of key osteogenic markers, and regulate BMP-2 signal transduction via extracellular signal-regulated kinases 1/2 (Erk1/2) phosphorylation in genetically engineered BMSCs in vitro. We also showed that SDF 1beta promotes the migratory response of CXC chemokine receptor 4 (CXCR4) expressing BMSCs in vitro. Taken together, these data support that SDF-1beta can play an important role in BMP-2-stimulated osteogenic differentiation of BMSCs and may exert its biological activity in both an autocrine and paracrine fashion. PMID- 22779448 TI - Molecular simulations of carbon dioxide and water: cation solvation. AB - Proposed carbon dioxide sequestration scenarios in sedimentary reservoirs require investigation into the interactions between supercritical carbon dioxide, brines, and the mineral phases found in the basin and overlying caprock. Molecular simulations can help to understand the partitioning of metal cations between aqueous solutions and supercritical carbon dioxide where limited experimental data exist. In this effort, we used classical molecular dynamics simulations to compare the solvation of alkali and alkaline-earth metal cations in water and liquid CO(2) at 300 K by combining a flexible simple point charge model for water and an accurate flexible force field for CO(2). Solvation energies for these cations are larger in water than in carbon dioxide, suggesting that they will partition preferentially into water. In both aqueous and CO(2) solutions, the solvation energies decrease with cation size and increase with cation charge. However, changes in solvation energy with ionic radii are smaller in CO(2) than in water suggesting that the partitioning of cations into CO(2) will increase with ion size. Simulations of the interface between aqueous solution and supercritical CO(2) support this suggestion in that some large cations (e.g., Cs(+) and K(+)) partition into the CO(2) phase, often with a partial solvation sphere of water molecules. PMID- 22779449 TI - Detection of simultaneous modulation of interaural time and level differences: effects of modulation rate and relative phase (L). AB - The binaural system is known to be sluggish, i.e., unable to track modulations in interaural parameters even at a relatively slow rate. The present study evaluated the binaural system's sensitivity to modulation phase rather than to modulation magnitude. The detectability of simultaneous modulations in interaural time and level differences with various relative phases were measured. It was found that for modulation rates up to 10-20 Hz, the detectability varied with the relative phase. This indicates that information about higher rates is lost at or below the level of cue integration. PMID- 22779450 TI - Asynchronous multiuser underwater acoustic communications (L). AB - An asynchronous multiuser system is proposed to support multiple-access underwater communications without the use of code-division multiple-access or a feedback channel. The rich multipath channels experienced by spatially separated users will be sufficient to ensure separation of collided packets at the base station. The iterative receiver will employ a combination of adaptive time reversal processing, matching pursuit, and successive interference cancellation in a block-wise fashion to achieve multiuser separability. Data collected during the KAM11 experiment are used to illustrate the system's capability in a dynamic, time-varying environment. PMID- 22779451 TI - The impact of early reflections on binaural cues. AB - Animals live in cluttered auditory environments, where sounds arrive at the two ears through several paths. Reflections make sound localization difficult, and it is thought that the auditory system deals with this issue by isolating the first wavefront and suppressing later signals. However, in many situations, reflections arrive too early to be suppressed, for example, reflections from the ground in small animals. This paper examines the implications of these early reflections on binaural cues to sound localization, using realistic models of reflecting surfaces and a spherical model of diffraction by the head. The fusion of direct and reflected signals at each ear results in interference patterns in binaural cues as a function of frequency. These cues are maximally modified at frequencies related to the delay between direct and reflected signals, and therefore to the spatial location of the sound source. Thus, natural binaural cues differ from anechoic cues. In particular, the range of interaural time differences is substantially larger than in anechoic environments. Reflections may potentially contribute binaural cues to distance and polar angle when the properties of the reflecting surface are known and stable, for example, for reflections on the ground. PMID- 22779452 TI - Amplitude-dependent internal friction, hysteretic nonlinearity, and nonlinear oscillations in a magnesite resonator. AB - The results of experimental and theoretical studies of low-frequency nonlinear acoustics phenomena (amplitude-dependent loss, resonance frequency shifts, and a generation of second and third harmonics) in a magnesite rod resonator are presented. Acceleration and velocity oscillograms of vibrations of the free boundary of the resonator caused by harmonic excitations were measured and analyzed. A theoretical description of the observed amplitude dependences was carried out within the framework of the phenomenological state equations that contain either of the two types of hysteretic nonlinearity (elastic and inelastic). The type of hysteresis and parameters of acoustic nonlinearity of magnesite were established from comparing the experimental measurements with the theoretical dependences. The values of the parameters were anomalously high even when compared to those of other strongly nonlinear polycrystalline materials such as granite, marble, limestone, sandstone, etc. PMID- 22779453 TI - Collective bubble dynamics near a surface in a weak acoustic standing wave field. AB - The transport of bubbles to a neighboring surface is very important in surface chemistry, bioengineering, and ultrasonic cleaning, etc. This paper proposes a multi-bubble transport method by using an acoustic standing wave field and establishes a model that explains the multi-bubble translation by expressing the balance between Bjerknes forces and hydrodynamic forces on a bubble in a liquid medium. Results indicated that the influence of primary Bjerknes force, secondary Bjerknes force, and buoyancy force on the bubble translation depends on the position of the target bubble in the acoustic field. Moreover, it was found that increasing the size of a bubble or pressure amplitude can accelerate the bubble motion and enhance the bubble-bubble interaction. The secondary Bjerknes force between two bubbles can switch from an attractive one when they oscillate in phase to a repulsive one when the bubble oscillations are out of phase. These findings provide an insight into the multi-bubble translation near a surface and can be applied to future bubble motion control studies, especially in drug delivery, sonoporation, and ultrasonic cleaning. PMID- 22779454 TI - A relation between multipath group velocity, mode number, and ray cycle distance. AB - Weston's ray invariant or "characteristic time" in a range-dependent environment is exactly equivalent to the Wentzel-Kramers-Brillouin phase integral for ducted normal modes. By considering a ray element it is shown that the ray invariant can also be written in terms of ray cycle distance and cycle time. This leads to a useful formula for group velocity in terms of cycle distance and mode number. Drawing a distinction between the ray and wave interpretation, the Airy phase (i.e., the existence of a group velocity minimum) can be included in this approach. Favorable comparisons are made with group velocities derived from a normal mode model. The relationship is valid for variable sound speed and variable bathymetry, and this is demonstrated numerically. The formula is applicable to active sonar, multipath pulse shape, target signatures, reverberation, tomography, and underwater communications. PMID- 22779455 TI - Acoustic field and array response uncertainties in stratified ocean media. AB - The change-of-variables theorem of probability theory is applied to compute acoustic field and array beam power probability density functions (pdfs) in uncertain ocean environments represented by stratified, attenuating ocean waveguide models. Computational studies for one and two-layer waveguides investigate the functional properties of the acoustic field and array beam power pdfs. For the studies, the acoustic parameter uncertainties are represented by parametric pdfs. The field and beam response pdfs are computed directly from the parameter pdfs using the normal-mode representation and the change-of-variables theorem. For two-dimensional acoustic parameter uncertainties of sound speed and attenuation, the field and beam power pdfs exhibit irregular functional behavior and singularities associated with stationary points of the mapping, defined by acoustic propagation, from the parameter space to the field or beam power space. Implications for the assessment of orthogonal polynomial expansion and other methods for computing acoustic field pdfs are discussed. PMID- 22779456 TI - Analysis of absorption performances of anechoic layers with steel plate backing. AB - Rubber layers with air-filled cavities or local resonance scatters can be used as anechoic coatings. A lot of researches have focused on the absorption mechanism of the anechoic coatings. As the anechoic coatings are bonded to the hull of submarine, the vibration of the hull should not be neglected when the analysis of the absorption characters is carried out. Therefore, it is more reasonable to treat the anechoic coating and the backing as a whole when the acoustic performance is analyzed. Considering the effects of the steel plate backing, the sound absorption performances on different models of anechoic coatings are investigated in this paper. The Finite Element Method is used to illustrate the vibrational behaviors of the anechoic coatings under the steel backings by which the displacement contours is obtained for analysis. The theoretical results show that an absorption peak is induced by the resonance of the steel slab and rubber layer. At the frequency of this absorption peak, the steel plate and the coating vibrates longitudinally like a mass-spring system in which the steel slab serves for mass and the coating layer is the spring. To illuminate the effects of the steel slab backing on the acoustic absorption, the thicknesses of the steel slab and the anechoic layer are discussed. Finally, an experiment is performed and the results show a good agreement with the theoretical analysis. PMID- 22779457 TI - Shipping noise in whale habitat: characteristics, sources, budget, and impact on belugas in Saguenay-St. Lawrence Marine Park hub. AB - A continuous car ferry line crossing the Saguenay Fjord mouth and traffic from the local whale-watching fleet introduce high levels of shipping noise in the heart of the Saguenay-St. Lawrence Marine Park. To characterize this noise and examine its potential impact on belugas, a 4-hydrophone array was deployed in the area and continuously recorded for five weeks in May-June 2009. The source levels of the different vessel types showed little dependence on vessel size or speed increase. Their spectral range covered 33 dB. Lowest noise levels occurred at night, when ferry crossing pace was reduced, and daytime noise peaked during whale-watching tour departures and arrivals. Natural ambient noise prevailed 9.4% of the time. Ferry traffic added 30-35 dB to ambient levels above 1 kHz during crossings, which contributed 8 to 14 dB to hourly averages. The whale-watching fleet added up to 5.6 dB during peak hours. Assuming no behavioral or auditory compensation, half of the time, beluga potential communication range was reduced to less than ~30% of its expected value under natural noise conditions, and to less than ~15% for one quarter of the time, with little dependence on call frequency. The echolocation band for this population of belugas was also affected by the shipping noise. PMID- 22779458 TI - Compressive matched-field processing. AB - Source localization by matched-field processing (MFP) generally involves solving a number of computationally intensive partial differential equations. This paper introduces a technique that mitigates this computational workload by "compressing" these computations. Drawing on key concepts from the recently developed field of compressed sensing, it shows how a low-dimensional proxy for the Green's function can be constructed by backpropagating a small set of random receiver vectors. Then the source can be located by performing a number of "short" correlations between this proxy and the projection of the recorded acoustic data in the compressed space. Numerical experiments in a Pekeris ocean waveguide are presented that demonstrate that this compressed version of MFP is as effective as traditional MFP even when the compression is significant. The results are particularly promising in the broadband regime where using as few as two random backpropagations per frequency performs almost as well as the traditional broadband MFP but with the added benefit of generic applicability. That is, the computationally intensive backpropagations may be computed offline independently from the received signals, and may be reused to locate any source within the search grid area. PMID- 22779459 TI - Fiber-optic, cantilever-type acoustic motion velocity hydrophone. AB - The interaction between fluid loaded fiber-optic cantilevers and a low frequency acoustic wave is investigated as the basis for an acoustic vector sensor. The displacements of the prototype cantilevers are measured with an integrated fiber laser strain sensor. A theoretical model predicting the frequency dependent shape of acoustically driven planar and cylindrical fiber-optic cantilevers incorporating effects of fluid viscosity is presented. The model demonstrates good agreement with the measured response of two prototype cantilevers, characterized with a vibrating water column, in the regime of Re >= 1. The performance of each cantilever geometry is also analyzed. Factors affecting the sensor performance such as fluid viscosity, laser mode profile, and support motion are considered. The planar cantilever is shown to experience the largest acoustically induced force and hence the highest acoustic responsivity. However, the cylindrical cantilever exhibits the smoothest response in water, due to the influence of viscous fluid damping, and is capable of two axis particle velocity measurement. These cantilevers are shown to be capable of achieving acoustic resolutions approaching the lowest sea-state ocean noise. PMID- 22779460 TI - Scattering characteristics of Lamb waves from debondings at structural features in composite laminates. AB - This article investigates the scattering characteristics of Lamb waves from a debonding at a structural feature in a composite laminate. This study specifically focuses on the use of the low frequency fundamental antisymmetric (A(0)) Lamb wave as the incident wave for debonding detection. Three-dimensional finite element (FE) simulations and experimental measurements are used to investigate the scattering phenomena. Good agreement is obtained between the FE simulations and experimental results. Detailed parameter studies are carried out to further investigate the relationship between the scattering amplitudes and debonding sizes. The results show that the amplitude of the scattered A(0) Lamb wave is sensitive to the debonding size, which indicates the potential of using the low frequency A(0) Lamb wave as the interrogating wave for debonding detection and monitoring. The findings of the study provide improved physical insights into the scattering phenomena, which are important to further advance damage detection techniques and optimize transducer networks. PMID- 22779461 TI - Model for bubble pulsation in liquid between parallel viscoelastic layers. AB - A model is presented for a pulsating spherical bubble positioned at a fixed location in a viscous, compressible liquid between parallel viscoelastic layers of finite thickness. The Green's function for particle displacement is found and utilized to derive an expression for the radiation load imposed on the bubble by the layers. Although the radiation load is derived for linear harmonic motion it may be incorporated into an equation for the nonlinear radial dynamics of the bubble. This expression is valid if the strain magnitudes in the viscoelastic layer remain small. Dependence of bubble pulsation on the viscoelastic and geometric parameters of the layers is demonstrated through numerical simulations. PMID- 22779462 TI - Radial and translational oscillations of an acoustically levitated bubble in aqueous ethanol solutions. AB - The radial and translational oscillations of a single cavitation bubble in a standing ultrasound wave were investigated experimentally at various driving acoustic pressures for aqueous ethanol solutions with different bulk molar fractions of ethanol range of 0-1.3 * 10(-3). The results show that both the lower and upper stability thresholds of the acoustic driving pressure decreased as the concentration of ethanol was increased. At a given driving pressure the ambient and maximum bubble sizes increased with increasing ethanol concentration. In addition, as the ethanol was increased, the sonoluminescence intensity decreased while the bubble dynamics remained largely unchanged. The translational oscillation of the levitated bubble, however, became increasingly violent with increasing ethanol concentration. The displacement of the bubble reached 0.7 mm at the highest concentration studied (1.3 * 10(-3)) and the maximum bubble size was found to change as the bubble jumped up and down. This bubble translation may be responsible for the decrease of the acoustic driving pressure threshold and suggests that repetitive injection of ethanol molecules into the bubble takes place. These results may account for the different sensitivities of single bubble and multi-bubble sonoluminescence to the presence of volatile additives. PMID- 22779463 TI - An acousto-optic beamformer. AB - There is a great variety of beamforming techniques that can be used for localization of sound sources. The differences among them usually lie in the array layout or in the specific signal processing algorithm used to compute the beamforming output. Any beamforming system consists of a finite number of transducers, which makes beamforming methods vulnerable to spatial aliasing above a certain frequency. The present work uses the acousto-optic effect, i.e., the interaction between sound and light, to localize sound sources in a plane. The use of a beam of light as the sensing element is equivalent to a continuous line aperture with an infinite number of microphones. This makes the proposed acousto optic beamformer immune to spatial aliasing. This unique feature is illustrated by means of simulations and experimental results within the entire audible frequency range. For ease of comparison, the study is supplemented with measurements carried out with a line array of microphones. PMID- 22779465 TI - Theoretical investigations of energy harvesting efficiency from structural vibrations using piezoelectric and electromagnetic oscillators. AB - Conversion of ambient vibrational energy into electric power has been the impetus of much modern research. The traditional analysis has focused on absolute electrical power output from the harvesting devices and efficiency defined as the convertibility of an infinite resource of vibration excitation into power. This perspective has limited extensibility when applying resonant harvesters to host resonant structures when the inertial influence of the harvester is more significant. Instead, this work pursues a fundamental understanding of the coupled dynamics of a main mass-spring-damper system to which an electromagnetic or piezoelectric mass-spring-damper is attached. The governing equations are derived, a metric of efficiency is presented, and analysis is undertaken. It is found that electromagnetic energy harvesting efficiency and maximum power output is limited by the strength of the coupling such that no split system resonances are induced for a given mass ratio. For piezoelectric harvesters, only the coupling strength and certain design requirements dictate maximum power and efficiency achievable. Since the harvesting circuitry must "follow" the split resonances as the piezoelectric harvesters become more massive, the optimum design of piezoelectric harvesters appears to be more involved than for electromagnetic devices. PMID- 22779464 TI - Frequency-radial duality based photoacoustic image reconstruction. AB - Photoacoustic image reconstruction algorithms are usually slow due to the large sizes of data that are processed. This paper proposes a method for exact photoacoustic reconstruction for the spherical geometry in the limiting case of a continuous aperture and infinite measurement bandwidth that is faster than existing methods namely (1) backprojection method and (2) the Norton-Linzer method [S. J. Norton and M. Linzer, "Ultrasonic reflectivity imaging in three dimensions: Exact inverse scattering solution for plane, cylindrical and spherical apertures," Biomedical Engineering, IEEE Trans. BME 28, 202-220 (1981)]. The initial pressure distribution is expanded using a spherical Fourier Bessel series. The proposed method estimates the Fourier Bessel coefficients and subsequently recovers the pressure distribution. A concept of frequency-radial duality is introduced that separates the information from the different radial basis functions by using frequencies corresponding to the Bessel zeros. This approach provides a means to analyze the information obtained given a measurement bandwidth. Using order analysis and numerical experiments, the proposed method is shown to be faster than both the backprojection and the Norton-Linzer methods. Further, the reconstructed images using the proposed methodology were of similar quality to the Norton-Linzer method and were better than the approximate backprojection method. PMID- 22779466 TI - Wave based analysis of the Green's function for a layered cylindrical shell. AB - Cylindrical shells composed of concentric layers may be designed to affect the way that elastic waves are generated and propagated, particularly when some layers are anisotropic. To aid the design process, the present work develops a wave based analysis of the Green's function for a layered cylindrical shell in which the response is given as a sum of waves propagating in the axial coordinate. The analysis assumes linear Hookean materials for each layer. It uses finite element discretizations in the radial coordinate and Fourier series expansions in the circumferential coordinate, leading to linear equations in the axial wavenumber domain that relate shell displacements and forces. Inversion to the axial domain is accomplished via a state-space formulation that is evaluated using residue integration. The resulting expression for the Green's function for each circumferential harmonic is a summation over the natural waves of the shell. The finite element discretization in the radial direction allows the approach to be used for arbitrarily thick shells. The approach is benchmarked to results from an isotropic shell and numerical examples are given for a shell composed of a fiber-reinforced material. The numerical examples illustrate the effect of fiber orientation on the Green's function. PMID- 22779467 TI - Characterization of mechanical properties of a hollow cylinder with zero group velocity Lamb modes. AB - Hollow cylinders used in the industry must be regularly inspected. Elastic guided waves, similar to Lamb modes in a plate, can propagate in the axial direction or around the circumference. They are sensitive to geometrical and mechanical parameters of the cylindrical shell. The objective of this paper is to show that zero group velocity (ZGV) Lamb modes can be used to bring out anisotropy and to measure elastic constants of the material. This study provides experimental and numerical investigations on a Zirconium alloy tube extensively used by the nuclear industry in reactor core components. A non-contact method, based on laser ultrasound techniques and ZGV Lamb modes, demonstrates that the difference observed between axial and circumferential guided waves cannot be explained by an isotropic model. Then, a transverse isotropic model is used for the Zircaloy tube. Four of the five elastic constants are directly extracted from ZGV resonance frequencies. The last one is deduced from the measured dispersion spectra. With this complete set of constants, a good agreement is obtained between theoretical and experimental dispersion curves for both axially and circumferentially propagating guided waves. PMID- 22779468 TI - Surface decomposition method for near-field acoustic holography. AB - Near-field acoustic holography reconstruction of the acoustic field at the surface of an arbitrarily shaped radiating structure from pressure measurements at a nearby conformal surface is obtained from the solution of a boundary integral equation. This integral equation is discretized using the equivalent source method and transformed into a matrix system that can be solved using iterative regularization methods that counteract the effect of noise on the measurements. This work considers the case when the resultant matrix system is so large that it cannot be explicitly formed and iterative methods of solution cannot be directly implemented. In this case the method of surface decomposition is proposed, where the measurement surface is divided into smaller nonoverlapping subsurfaces. Each subsurface is used to form a smaller matrix system that is solved and the result joined together to generate a global solution to the original matrix system. Numerically generated data are used to study the use of subsurface extensions to increase the continuity of the global solution, and investigate the size of the subsurfaces, as well as the distance between the measurement and the vibrating surface. Finally a vibrating ship hull structure is considered as a physical example to apply and validate the proposed methodology. PMID- 22779469 TI - Minimization of the mean square velocity response of dynamic structures using an active-passive dynamic vibration absorber. AB - An optimal design of a hybrid vibration absorber (HVA) with a displacement and a velocity feedback for minimizing the velocity response of the structure based on the H(2) optimization criterion is proposed. The objective of the optimal design is to reduce the total vibration energy of the vibrating structure under wideband excitation, i.e., the total area under the velocity response spectrum is minimized in this criterion. One of the inherent limitations of the traditional passive vibration absorber is that its vibration suppression is low if the mass ratio between the absorber mass and the mass of the primary structure is low. The active element of the proposed HVA helps further reduce the vibration of the controlled structure, and it can provide very good vibration absorption performance even at a low mass ratio. Both the passive and active elements are optimized together for the minimization of the mean square velocity of the primary system as well as the active force required in the HVA. The proposed HVA was tested on single degree-of-freedom (SDOF) and continuous vibrating structures and compared to the traditional passive vibration absorber. PMID- 22779470 TI - An application of the Peano series expansion to predict sound propagation in materials with continuous pore stratification. AB - This work reports on an application of the state vector (Stroh) formalism and Peano series expansion to solve the problem of sound propagation in a material with continuous pore stratification. An alternative Biot formulation is used to link the equivalent velocity in the oscillatory flow in the material pores with the acoustic pressure gradient. In this formulation, the complex dynamic density and bulk modulus are predicted using the equivalent fluid flow model developed by Horoshenkov and Swift [J. Acoust. Soc. Am. 110(5), 2371-2378 (2001)] under the rigid frame approximation. This model is validated against experimental data obtained for a 140 mm thick material specimen with continuous pore size stratification and relatively constant porosity. This material has been produced from polyurethane binder solution placed in a container with a vented top and sealed bottom to achieve a gradient in the reaction time which caused a pore size stratification to develop as a function of depth [Mahasaranon et al., J. Appl. Phys. 111, 084901 (2012)]. It is shown that the acoustical properties of this class of materials can be accurately predicted with the adopted theoretical model. PMID- 22779471 TI - Blast noise characteristics as a function of distance for temperate and desert climates. AB - Variability in received sound levels were investigated at distances ranging from 4 m to 16 km from a typical blast source in two locations with different climates and terrain. Four experiments were conducted, two in a temperate climate with a hilly terrain and two in a desert climate with a flat terrain, under a variety of meteorological conditions. Sound levels were recorded in three different directions around the source during the summer and winter seasons in each location. Testing occurred over the course of several days for each experiment during all 24 h of the day, and meteorological data were gathered throughout each experiment. The peak levels (L(Pk)), C-weighted sound exposure levels (CSEL), and spectral characteristics of the received sound pressure levels were analyzed. The results show high variability in L(Pk) and CSEL at distances beyond 2 km from the source for each experiment, which was not clearly explained by the time of day the blasts occurred. Also, as expected, higher frequency energy is attenuated more drastically than the lower frequency energy as the distance from the source increases. These data serve as a reference for long-distance blast sound propagation. PMID- 22779472 TI - Acoustic energy density distribution and sound intensity vector field inside coupled spaces. AB - In this paper, the modal expansion method supported by a computer implementation has been used to predict steady-state distributions of the potential and kinetic energy densities, and the active and reactive sound intensities inside two coupled enclosures. The numerical study was dedicated to low-frequency room responses. Calculation results have shown that the distribution of energetic quantities in coupled spaces is strongly influenced by the modal localization. Appropriate descriptors of the localization effect were introduced to identify localized modes. As was evidenced by numerical data, the characteristic objects in the active intensity field are vortices positioned irregularly inside the room. It was found that vortex centers lie exactly on the lines corresponding to zeros of the eigenfunction for a dominant mode. Finally, an impact of the wall impedance on the quantitative relationship between the active and reactive intensities was analyzed and it was concluded that for very small sound damping the behavior of the sound intensity inside the room space is essentially only oscillatory. PMID- 22779473 TI - Low frequency sound propagation in activated carbon. AB - Activated carbon can adsorb and desorb gas molecules onto and off its surface. Research has examined whether this sorption affects low frequency sound waves, with pressures typical of audible sound, interacting with granular activated carbon. Impedance tube measurements were undertaken examining the resonant frequencies of Helmholtz resonators with different backing materials. It was found that the addition of activated carbon increased the compliance of the backing volume. The effect was observed up to the highest frequency measured (500 Hz), but was most significant at lower frequencies (at higher frequencies another phenomenon can explain the behavior). An apparatus was constructed to measure the effective porosity of the activated carbon as well as the number of moles adsorbed at sound pressures between 104 and 118 dB and low frequencies between 20 and 55 Hz. Whilst the results were consistent with adsorption affecting sound propagation, other phenomena cannot be ruled out. Measurements of sorption isotherms showed that additional energy losses can be caused by water vapor condensing onto and then evaporating from the surface of the material. However, the excess absorption measured for low frequency sound waves is primarily caused by decreases in surface reactance rather than changes in surface resistance. PMID- 22779474 TI - Speakers' comfort and voice level variation in classrooms: laboratory research. AB - Teachers adjust their voice levels under different classroom acoustics conditions, even in the absence of background noise. Laboratory experiments have been conducted in order to understand further this relationship and to determine optimum room acoustic conditions for speaking. Under simulated acoustic environments, talkers do modify their voice levels linearly with the measure voice support, and the slope of this relationship is referred to as room effect. The magnitude of the room effect depends highly on the instruction used and on the individuals. Group-wise, the average room effect ranges from -0.93 dB/dB, with free speech, to -0.1 dB/dB with other less demanding communication tasks as reading and talking at short distances. The room effect for some individuals can be as strong as -1.7 dB/dB. A questionnaire investigation showed that the acoustic comfort for talking in classrooms, in the absence of background noise, is correlated to the decay times derived from an impulse response measured from the mouth to the ears of a talker, and that there is a maximum of preference for decay times between 0.4 and 0.5 s. Teachers with self-reported voice problems prefer higher decay times to speak in than their healthy colleagues. PMID- 22779475 TI - Acoustic analysis by spherical microphone array processing of room impulse responses. AB - Spherical microphone arrays have been recently used for room acoustics analysis, to detect the direction-of-arrival of early room reflections, and compute directional room impulse responses and other spatial room acoustics parameters. Previous works presented methods for room acoustics analysis using spherical arrays that are based on beamforming, e.g., delay-and-sum, regular beamforming, and Dolph-Chebyshev beamforming. Although beamforming methods provide useful directional selectivity, optimal array processing methods can provide enhanced performance. However, these algorithms require an array cross-spectrum matrix with a full rank, while array data based on room impulse responses may not satisfy this condition due to the single frame data. This paper presents a smoothing technique for the cross-spectrum matrix in the frequency domain, designed for spherical microphone arrays, that can solve the problem of low rank when using room impulse response data, therefore facilitating the use of optimal array processing methods. Frequency smoothing is shown to be performed effectively using spherical arrays, due to the decoupling of frequency and angular components in the spherical harmonics domain. Experimental study with data measured in a real auditorium illustrates the performance of optimal array processing methods such as MUSIC and MVDR compared to beamforming. PMID- 22779476 TI - Time-domain characterization of the acoustic damping of a perforated liner with bias flow. AB - Combustion instabilities are caused by the interaction of unsteady heat releases and acoustic waves. To mitigate combustion instabilities, perforated liners, typically subjected to a low Mach number bias flow (a cooling flow through perforated holes), are fitted along the bounding walls of a combustor. They dissipate the acoustic waves by generating vorticity at the rims of perforated apertures. To investigate the absorption of plane waves by a perforated liner with bias flow, a time-domain numerical model of a cylindrical lined duct is developed. The liners' damping mechanism is characterized by using a time-domain "compliance." The development of such time-domain compliance is based on simplified or unsimplified Rayleigh conductivity. Numerical simulations of two different configurations of lined duct systems are performed by combining a 1D acoustic wave model with the compliance model. Comparison is then made between the results from the present models, and those from the experiment and the frequency-domain model of previous investigation [Eldredge and Dowling, J. Fluid Mech. 485, 307-335(2003)]. Good agreement is observed. This confirms that the present model can be used to simulate the propagation and dissipation of acoustic plane waves in a lined duct in real-time. PMID- 22779478 TI - Phase mapping of acoustic sources by beamforming and iterative far field monopole substitution. AB - The first aim of this paper is to give emphasis to the importance of assessing phase information when reconstructing and mapping a sound field. In fact, in acoustic analysis phase distribution is frequently simply either not considered or ignored, even though it can supply very useful information for the understanding of the mapping itself or for further analyses. In this paper a procedure to carry out phase mapping of acoustic sources in beamforming measurement is illustrated. The second aim of this paper is to propose a straightforward iterative optimization algorithm based on the monopole substitution starting from beamforming results. It allows for the reconstruction of sound field without the use of any matrix inversion. Both numerical and experimental validations of the method are presented. Results shown hereafter prove the effectiveness of the approach. PMID- 22779477 TI - Recovery of individual head-related transfer functions from a small set of measurements. AB - Head-related transfer functions (HRTFs) vary with individuals, and in practice, measuring HRTFs with high directional resolution for each individual is tiresome. Based on a basis functions representation of HRTFs, the present work proposes a method for recovering individual HRTFs from a small set of measurements. The HRTFs are represented by a combination of a small set of spatial basis functions (SBFs) with frequency- and individual-dependent weights. The SBFs are derived by applying spatial principal component analysis to a baseline HRTF dataset with high directional resolution. The individual weights for any subject outside the dataset are estimated from measurements at a few source directions, and then the HRTFs with high directional resolution are recovered by combining the SBFs and the individual weights. In an illustrative case, the SBFs derived from a baseline dataset that includes 20 subjects are used to recover the HRTF magnitudes for six subjects outside the baseline dataset. Results show that individual HRTF magnitudes can be recovered from measurements at 73 directions with a mean signal to-distortion ratio of 19 dB. The proposed method is also applicable to recovering head-related impulse responses. The results of psychoacoustic experiments indicate that in most cases the recovered and measured HRTFs are indistinguishable. PMID- 22779479 TI - Comodulation masking release: effects of training and experimental design on use of within- and across-channel cues. AB - The effects of training and experimental design on comodulation masking release (CMR) were assessed. The study of Dau et al. [(2009), J. Acoust. Soc. Am. 125, 2182-2188], which used auditory-grouping manipulations to distinguish the use of within- and across-channel cues to CMR, was replicated in Experiment One but using naive subjects and an experimental design that minimized familiarization with the cues. Subjects made effective use of within- but not across-channel cues. Experiment Two examined training effects over more testing sessions, across four experimental designs (to minimize or maximize repeated exposure to the cues) and using an auditory grouping manipulation ("postcursors") to distinguish the use of within- and across-channel cues. Naive subjects were tested with either two or four flanking bands (FBs), to determine if training effects varied with the amount of FB information. Within-channel cues could be used from the outset, but effective use of across-channel cues required training when they were less salient. Increased repeated exposure enhanced the effects of training. Experiment Three tested naive subjects using two FBs, but with noise presented continuously and a different auditory grouping manipulation, after Grose et al. [(2009), J. Acoust. Soc. Am. 125, 282-293]. CMR was large from the outset. PMID- 22779480 TI - Notionally steady background noise acts primarily as a modulation masker of speech. AB - Stone et al. [J. Acoust. Soc Am. 130, 2874-2881 (2011)], using vocoder processing, showed that the envelope modulations of a notionally steady noise were more effective than the envelope energy as a masker of speech. Here the same effect is demonstrated using non-vocoded signals. Speech was filtered into 28 channels. A masker centered on each channel was added to the channel signal at a target-to-background ratio of -5 or -10 dB. Maskers were sinusoids or noise bands with bandwidth 1/3 or 1 ERB(N) (ERB(N) being the bandwidth of "normal" auditory filters), synthesized with Gaussian (GN) or low-noise (LNN) statistics. To minimize peripheral interactions between maskers, odd-numbered channels were presented to one ear and even to the other. Speech intelligibility was assessed in the presence of each "steady" masker and that masker 100% sinusoidally amplitude modulated (SAM) at 8 Hz. Intelligibility decreased with increasing envelope fluctuation of the maskers. Masking release, the difference in intelligibility between the SAM and its "steady" counterpart, increased with bandwidth from near-zero to around 50 percentage points for the 1-ERB(N) GN. It is concluded that the sinusoidal and GN maskers behaved primarily as energetic and modulation maskers, respectively. PMID- 22779481 TI - The effects of noise-bandwidth, noise-fringe duration, and temporal signal location on the binaural masking-level difference. AB - The effects of forward and backward noise fringes on binaural signal detectability were investigated. Masked thresholds for a 12-ms, 250-Hz, sinusoidal signal masked by Gaussian noise, centered at 250 Hz, with bandwidths from 3 to 201 Hz, were obtained in N(0)S(0) and N(0)S(pi) configurations. The signal was (a) temporally centered in a 12-ms noise burst (no fringe), (b) presented at the start of a 600-ms noise burst (backward fringe), or (c) temporally centered in a 600-ms noise burst (forward-plus-backward fringe). For noise bandwidths between 3 and 75 Hz, detection in N(0)S(0) improved with the addition of a backward fringe, improving further with an additional forward fringe; there was little improvement in N(0)S(pi). The binaural masking-level difference (BMLD) increased from 0 to 8 dB with a forward-plus-backward fringe as noise bandwidths increased to 100 Hz, increasing slightly to 10 dB at 201 Hz. This two-stage increase was less pronounced with a backward fringe. With no fringe, the BMLD was about 10-14 dB at all bandwidths. Performance appears to result from the interaction of across-time and across-frequency listening strategies and the possible effects of gain reduction and suppression, which combine in complex ways. Current binaural models are, as yet, unable to account fully for these effects. PMID- 22779482 TI - Pitch perception of concurrent harmonic tones with overlapping spectra. AB - Fundamental frequency difference limens (F0DLs) were measured for a target harmonic complex tone with nominal fundamental frequency (F0) of 200 Hz, in the presence and absence of a harmonic masker with overlapping spectrum. The F0 of the masker was 0, +/- 3, or +/- 6 semitones relative to 200 Hz. The stimuli were bandpass filtered into three regions: 0-1000 Hz (low, L), 1600-2400 Hz (medium, M), and 2800-3600 Hz (high, H), and a background noise was used to mask combination tones and to limit the audibility of components falling on the filter skirts. The components of the target or masker started either in cosine or random phase. Generally, the effect of F0 difference between target and masker was small. For the target alone, F0DLs were larger for random than cosine phase for region H. For the target plus masker, F0DLs were larger when the target had random phase than cosine phase for regions M and H. F0DLs increased with increasing center frequency of the bandpass filter. Modeling using excitation patterns and "summary autocorrelation" and "stabilized auditory image" models suggested that use of temporal fine structure information can account for the small F0DLs obtained when harmonics are barely, if at all, resolved. PMID- 22779483 TI - Spatial cues alone produce inaccurate sound segregation: the effect of interaural time differences. AB - To clarify the role of spatial cues in sound segregation, this study explored whether interaural time differences (ITDs) are sufficient to allow listeners to identify a novel sound source from a mixture of sources. Listeners heard mixtures of two synthetic sounds, a target and distractor, each of which possessed naturalistic spectrotemporal correlations but otherwise lacked strong grouping cues, and which contained either the same or different ITDs. When the task was to judge whether a probe sound matched a source in the preceding mixture, performance improved greatly when the same target was presented repeatedly across distinct distractors, consistent with previous results. In contrast, performance improved only slightly with ITD separation of target and distractor, even when spectrotemporal overlap between target and distractor was reduced. However, when subjects localized, rather than identified, the sources in the mixture, sources with different ITDs were reported as two sources at distinct and accurately identified locations. ITDs alone thus enable listeners to perceptually segregate mixtures of sources, but the perceived content of these sources is inaccurate when other segregation cues, such as harmonicity and common onsets and offsets, do not also promote proper source separation. PMID- 22779485 TI - Spatial release from masking in children with normal hearing and with bilateral cochlear implants: effect of interferer asymmetry. AB - Spatial release from masking (SRM) was measured in groups of children with bilateral cochlear implants (BiCIs, average ages 6.0 and 7.9 yr) and with normal hearing (NH, average ages 5.0 and 7.8 yr). Speech reception thresholds (SRTs) were measured for target speech in front (0 degrees ), and interferers in front, distributed asymmetrically toward the right (+90 degrees /+90 degrees ) or distributed symmetrically toward the right and left (+90 degrees /-90 degrees ). In the asymmetrical condition both monaural "better ear" and binaural cues are available. In the symmetrical condition, listeners rely heavily on binaural cues to segregate sources. SRM was computed as the difference between SRTs in the front condition and SRTs in either the asymmetrical or symmetrical conditions. Results showed that asymmetrical SRM was smaller in BiCI users than NH children. Furthermore, NH children showed symmetrical SRM, suggesting they are able to use binaural cues for source segregation, whereas children with BiCIs had minimal or absent symmetrical SRM. These findings suggest that children who receive BiCIs can segregate speech from noise under conditions that maximize monaural better ear cues. Limitations in the CI devices likely play an important role in limiting SRM. Thus, improvement in spatial hearing abilities in children with BiCIs may require binaural processing strategies. PMID- 22779486 TI - Enhancement of temporal cues to pitch in cochlear implants: effects on pitch ranking. AB - The abilities to hear changes in pitch for sung vowels and understand speech using an experimental sound coding strategy (eTone) that enhanced coding of temporal fundamental frequency (F0) information were tested in six cochlear implant users, and compared with performance using their clinical (ACE) strategy. In addition, rate- and modulation rate-pitch difference limens (DLs) were measured using synthetic stimuli with F0s below 300 Hz to determine psychophysical abilities of each subject and to provide experience in attending to rate cues for the judgment of pitch. Sung-vowel pitch ranking tests for stimuli separated by three semitones presented across an F0 range of one octave (139-277 Hz) showed a significant benefit for the experimental strategy compared to ACE. Average d-prime (d') values for eTone (d' = 1.05) were approximately three time larger than for ACE (d' = 0.35). Similar scores for both strategies in the speech recognition tests showed that coding of segmental speech information by the experimental strategy was not degraded. Average F0 DLs were consistent with results from previous studies and for all subjects were less than or equal to approximately three semitones for F0s of 125 and 200 Hz. PMID- 22779484 TI - Apparent auditory source width insensitivity in older hearing-impaired individuals. AB - Previous studies have shown a loss in the precision of horizontal localization responses of older hearing-impaired (HI) individuals, along with potentially poorer neural representations of sound-source location. These deficits could be the result or corollary of greater difficulties in discriminating spatial images, and the insensitivity to punctate sound sources. This hypothesis was tested in three headphone-presentation experiments varying interaural coherence (IC), the cue most associated with apparent auditory source width. First, thresholds for differences in IC were measured for a broad sampling of participants. Older HI participants were significantly worse at discriminating IC across reference values than younger normal-hearing participants. These results are consistent with senescent increases in temporal jitter. Performance decreased with age, a finding corroborated in a second discrimination experiment using a separate group of participants matched for hearing loss. This group also completed a third, visual experiment, with both a cross-mapping task where they drew the size of the sound they heard and the identification task where they chose the image that best corresponded to what they heard. The results from the visual tasks indicate that older HI individuals do not hear punctate images and are relatively insensitive to changes in width based on IC. PMID- 22779487 TI - Effect of source-tract acoustical coupling on the oscillation onset of the vocal folds. AB - This paper analyzes the interaction between the vocal folds and vocal tract at phonation onset due to the acoustical coupling between both systems. Data collected from a mechanical replica of the vocal folds show that changes in vocal tract length induce fluctuations in the oscillation threshold values of both subglottal pressure and frequency. Frequency jumps and maxima of the threshold pressure occur when the oscillation frequency is slightly above a vocal tract resonance. Both the downstream and upstream vocal tracts may produce those same effects. A simple mathematical model is next proposed, based on a lumped description of tissue mechanics, quasi-steady flow and one-dimensional acoustics. The model shows that the frequency jumps are produced by saddle-node bifurcations between limit cycles forming a classical pattern of a cusp catastrophe. The transition from a low frequency oscillation to a high frequency one may be achieved through two different paths: in case of a large acoustical coupling (narrow vocal tract) or high subglottal pressure, the bifurcations are crossed, which causes a frequency jump with a hysteresis loop. By reducing the acoustical coupling (wide vocal tract) or the subglottal pressure, a path around the bifurcations may be followed with a smooth frequency variation. PMID- 22779488 TI - A study of jaw coarticulatory resistance and aggressiveness for Catalan consonants and vowels. AB - The goal of this study is to investigate coarticulatory resistance and aggressiveness for the jaw in Catalan consonants and vowels and, more specifically, for the alveolopalatal nasal //[symbol see text]/ and for dark /l/ for which there is little or no data on jaw position and coarticulation. Jaw movement data for symmetrical vowel-consonant-vowel sequences with the consonants /p, n, l, s, ?, [ symbol see text], k/ and the vowels /i, a, u/ were recorded by three Catalan speakers with a midsagittal magnetometer. Data reveal that jaw height is greater for /s, ?/ than for /p, [see text]/, which is greater than for /n, l, k/ during the consonant, and for /i, u/ than for /a/ during the vowel. Differences in coarticulatory variability among consonants and vowels are inversely related to differences in jaw height, i.e., fricatives and high vowels are most resistant, and /n, l, k/ and the low vowel are least resistant. Moreover, coarticulation resistant phonetic segments exert more prominent effects and, thus, are more aggressive than segments specified for a lower degree of coarticulatory resistance. Data are discussed in the light of the degree of articulatory constraint model of coarticulation. PMID- 22779489 TI - Post-low bouncing in Mandarin Chinese: acoustic analysis and computational modeling. AB - Post-low bouncing is a phenomenon whereby after reaching a very low pitch in a low lexical tone, F(0) bounces up and then gradually drops back in the following syllables. This paper reports the results of an acoustic analysis of the phenomenon in two Mandarin Chinese corpora and presents a simple mechanical model that can effectively simulate this bouncing effect. The acoustic analysis shows that most of the F(0) dynamic features profiling the bouncing effect strongly correlate with the amount of F(0) lowering in the preceding low-tone syllable, and that the additional F(0) raising commences at the onset of the first post-low syllable. Using the quantitative Target Approximation model, this bouncing effect was simulated by adding an acceleration adjustment to the initial F(0) state of the first post-low syllable. A highly linear relation between F(0) lowering and estimated acceleration adjustment was found. This relation was then used to effectively simulate the bouncing effect in both the neutral tone and the full tones. The results of the analysis and simulation are consistent with the hypothesis that the bouncing effect is due to a temporary perturbation of the balance between antagonistic forces in the laryngeal control in producing a very low pitch. PMID- 22779490 TI - Horizontal directivity of low- and high-frequency energy in speech and singing. AB - Speech and singing directivity in the horizontal plane was examined using simultaneous multi-channel full-bandwidth recordings to investigate directivity of high-frequency energy, in particular. This method allowed not only for accurate analysis of running speech using the long-term average spectrum, but also for examination of directivity of separate transient phonemes. Several vocal production factors that could affect directivity were examined. Directivity differences were not found between modes of production (speech vs singing) and only slight differences were found between genders and production levels (soft vs normal vs loud), more pronounced in the higher frequencies. Large directivity differences were found between specific voiceless fricatives, with /s,?/ more directional than /f,theta/ in the 4, 8, 16 kHz octave bands. PMID- 22779491 TI - The influence of alcoholic intoxication on the fundamental frequency of female and male speakers. AB - This study investigates long-term features and utterance contours of fundamental frequency (f0) derived from the German Alcohol Language Corpus. The corpus comprises read, spontaneous, and command&control speech uttered by 148 speakers of both genders and various age groups when sober and intoxicated. f0 median, f0 range, and f0 contours are analyzed for intoxication and interactions with gender and age. Contours are compared both directly (root mean squared error, statistical correlation, or the Euclidean distance in the spectral space of the contour) and by parameterization of the contour using discrete cosine transform and the first and second moment of the lower contour spectrum. Results partly confirm earlier findings, i.e., f0 average and range are mostly raised with intoxication, and also suggest that the majority of speakers do not follow a general trend, but show idiosyncratic alterations to f0. f0 contours differ significantly with intoxication, but a more detailed analysis could not assign these changes to specific general form changes like decline or curvature. The results suggest that it is not possible to predict intoxication from f0 in a single model across different speakers. Instead a speaker-dependent model to account for the individual speaker behavior is proposed. PMID- 22779492 TI - Time-domain noise reduction based on an orthogonal decomposition for desired signal extraction. AB - This paper addresses the problem of noise reduction in the time domain where the clean speech sample at every time instant is estimated by filtering a vector of the noisy speech signal. Such a clean speech estimate consists of both the filtered speech and residual noise (filtered noise) as the noisy vector is the sum of the clean speech and noise vectors. Traditionally, the filtered speech is treated as the desired signal after noise reduction. This paper proposes to decompose the clean speech vector into two orthogonal components: one is correlated and the other is uncorrelated with the current clean speech sample. While the correlated component helps estimate the clean speech, it is shown that the uncorrelated component interferes with the estimation, just as the additive noise. Based on this orthogonal decomposition, the paper presents a way to define the error signal and cost functions and addresses the issue of how to design different optimal noise reduction filters by optimizing these cost functions. Specifically, it discusses how to design the maximum SNR filter, the Wiener filter, the minimum variance distortionless response (MVDR) filter, the tradeoff filter, and the linearly constrained minimum variance (LCMV) filter. It demonstrates that the maximum SNR, Wiener, MVDR, and tradeoff filters are identical up to a scaling factor. It also shows from the orthogonal decomposition that many performance measures can be defined, which seem to be more appropriate than the traditional ones for the evaluation of the noise reduction filters. PMID- 22779493 TI - Parametric plate-bridge dynamic filter model of violin radiativity. AB - A hybrid, deterministic-statistical, parametric "dynamic filter" model of the violin's radiativity profile [characterized by an averaged-over-sphere, mean square radiativity (R(omega)(2))] is developed based on the premise that acoustic radiation depends on (1) how strongly it vibrates [characterized by the averaged over-corpus, mean-square mobility (Y(omega)(2))] and (2) how effectively these vibrations are turned into sound, characterized by the radiation efficiency, which is proportional to (R(omega)(2))/(Y(omega)(2)). Two plate mode frequencies were used to compute 1st corpus bending mode frequencies using empirical trend lines; these corpus bending modes in turn drive cavity volume flows to excite the two lowest cavity modes A0 and A1. All widely-separated, strongly-radiating corpus and cavity modes in the low frequency deterministic region are then parameterized in a dual-Helmholtz resonator model. Mid-high frequency statistical regions are parameterized with the aid of a distributed-excitation statistical mobility function (no bridge) to help extract bridge filter effects associated with (a) bridge rocking mode frequency changes and (b) bridge-corpus interactions from 14-violin-average, excited-via-bridge (Y(omega)(2)) and (R(omega)(2)). Deterministic-statistical regions are rejoined at ~630 Hz in a mobility radiativity "trough" where all violin quality classes had a common radiativity. Simulations indicate that typical plate tuning has a significantly weaker effect on radiativity profile trends than bridge tuning. PMID- 22779494 TI - Scattering of acoustic waves by macroscopically inhomogeneous poroelastic tubes. AB - Wave propagation in macroscopically inhomogeneous porous materials has received much attention in recent years. For planar configurations, the wave equation, derived from the alternative formulation of Biot's theory of 1962, was reduced and solved recently: first in the case of rigid frame inhomogeneous porous materials and then in the case of inhomogeneous poroelastic materials in the framework of Biot's theory. This paper focuses on the solution of the full wave equation in cylindrical coordinates for poroelastic tubes in which the acoustic and elastic properties of the poroelastic tube vary in the radial direction. The reflection coefficient is obtained numerically using the state vector (or the so called Stroh) formalism and Peano series. This coefficient can then be used to straightforwardly calculate the scattered field. To validate the method of resolution, results obtained by the present method are compared to those calculated by the classical transfer matrix method in the case of a two-layer poroelastic tube. As an example, a long bone excited in the sagittal plane is considered. Finally, a discussion is given of ultrasonic time domain scattered field for various inhomogeneity profiles, which could lead to the prospect of long bone characterization. PMID- 22779495 TI - Shadow effects in simulated ultrasound images derived from computed tomography images using a focused beam tracing model. AB - Simulation of ultrasound images based on computed tomography (CT) data has previously been performed with different approaches. Shadow effects are normally pronounced in ultrasound images, so they should be included in the simulation. In this study, a method to capture the shadow effects has been developed, which makes the simulated ultrasound images appear more realistic. The method using a focused beam tracing model gives diffuse shadows that are similar to the ones observed in measurements on real objects. Ultrasound images of a cod (Gadus morhua) were obtained with a BK Medical 2202 ProFocus ultrasound scanner (BK Medical, Herlev, Denmark) equipped with a dedicated research interface giving access to beamformed radio frequency data. CT images were obtained with an Aquilion ONE Toshiba CT scanner (Toshiba Medical Systems Corp., Tochigi, Japan). CT data were mapped from Hounsfield units to backscatter strength, attenuation coefficients, and characteristic acoustic impedance. The focused beam tracing model was used to create maps of the transmission coefficient and scattering strength maps. Field II was then used to simulate an ultrasound image of 38.9 * 55.3 * 4.5 mm, using 10(6) point scatterers. As there is no quantitative method to assess quality of a simulated ultrasound image compared to a measured one, visual inspection was used for evaluation. PMID- 22779496 TI - Characterizing dusky dolphin sounds from Argentina and New Zealand. AB - Dusky dolphin (Lagenorhynchus obscurus) acoustic sounds were characterized by analyzing narrowband recordings [0-16 kHz in New Zealand (NZ) and 0-24 kHz in Argentina], and sounds in broadband recordings (0-200 kHz) were compared to their counterparts in down-sampled narrowband recordings (0-16 kHz). The most robust similarity between sounds present in broadband recordings and their counterparts in the down-sampled narrowband recordings was inter-click interval (ICI); ICI was therefore primarily used to characterize click sounds in narrowband recordings. In NZ and Argentina, distribution of ICIs was a continuum, although the distribution of ICIs in NZ had a somewhat bimodal tendency. In NZ, sounds that had smaller mean ICIs were more likely to have constant ICIs, and less likely to have increasing or decreasing ICIs. Similar to some other delphinids, dusky dolphins may use single, short duration sounds that have a constant ICI and closely spaced clicks for communication. No whistles were documented at either study site. Temporally structured sequences of burst pulses (i.e., sounds with ICI < about 10 ms) also occurred at both study sites, and these sequences contained 2-14 burst pulses that appeared closely matched aurally and in spectrograms and waveforms. PMID- 22779497 TI - Automating identification of avian vocalizations using time-frequency information extracted from the Gabor transform. AB - Based on the Gabor transform, a metric is developed and applied to automatically identify bird species from a sample of 568 digital recordings of songs/calls from 67 species of birds. The Gabor frequency-amplitude spectrum and the Gabor time amplitude profile are proposed as a means to characterize the frequency and time patterns of a bird song. An approach based on template matching where unknown song clips are compared to a library of known song clips is used. After adding noise to simulate the background environment and using an adaptive high-pass filter to de-noise the recordings, the successful identification rate exceeded 93% even at signal-to-noise ratios as low as 5 dB. Bird species whose songs/calls were dominated by low frequencies were more difficult to identify than species whose songs were dominated by higher frequencies. The results suggest that automated identification may be practical if comprehensive libraries of recordings that encompass the vocal variation within species can be assembled. PMID- 22779498 TI - Acoustic and diving behavior of sperm whales (Physeter macrocephalus) during natural and depredation foraging in the Gulf of Alaska. AB - Sperm whales have depredated black cod (Anoplopoma fimbria) from demersal longlines in the Gulf of Alaska for decades, but the behavior has recently spread in intensity and geographic coverage. Over a three-year period 11 bioacoustic tags were attached to adult sperm whales off Southeast Alaska during both natural and depredation foraging conditions. Measurements of the animals' dive profiles and their acoustic behavior under both behavioral modes were examined for statistically significant differences. Two rough categories of depredation are identified: "deep" and "shallow." "Deep depredating" whales consistently surface within 500 m of a hauling fishing vessel, have maximum dive depths greater than 200 m, and display significantly different acoustic behavior than naturally foraging whales, with shorter inter-click intervals, occasional bouts of high "creak" rates, and fewer dives without creaks. "Shallow depredating" whales conduct dives that are much shorter, shallower, and more acoustically active than both the natural and deep depredating behaviors, with median creak rates three times that of natural levels. These results suggest that depredation efforts might be measured remotely with passive acoustic monitoring at close ranges. PMID- 22779499 TI - Time domain attenuation estimation method from ultrasonic backscattered signals. AB - Ultrasonic attenuation is important not only as a parameter for characterizing tissue but also for compensating other parameters that are used to classify tissues. Several techniques have been explored for estimating ultrasonic attenuation from backscattered signals. In the present study, a technique is developed to estimate the local ultrasonic attenuation coefficient by analyzing the time domain backscattered signal. The proposed method incorporates an objective function that combines the diffraction pattern of the source/receiver with the attenuation slope in an integral equation. The technique was assessed through simulations and validated through experiments with a tissue mimicking phantom and fresh rabbit liver samples. The attenuation values estimated using the proposed technique were compared with the attenuation estimated using insertion loss measurements. For a data block size of 15 pulse lengths axially and 15 beamwidths laterally, the mean attenuation estimates from the tissue mimicking phantoms were within 10% of the estimates using insertion loss measurements. With a data block size of 20 pulse lengths axially and 20 beamwidths laterally, the error in the attenuation values estimated from the liver samples were within 10% of the attenuation values estimated from the insertion loss measurements. PMID- 22779566 TI - Low-frequency resonance of an oblate spheroidal cavity in a soft elastic medium. AB - Axisymmetric monopole resonances of an oblate spheroidal cavity in a soft elastic medium are computed using both separation of variables and finite-element approaches. The resonances are obtained for compression wavelengths much longer than the cavity size and thus have a low-frequency character. Resonant frequencies for high-aspect-ratio oblate spheroids (either air-filled or evacuated) are found to be significantly lower than their spherical counterparts with equivalent volume. This finding contrasts with the case of an air bubble in water which features weak shape dependence. The results are relevant to the design of locally-resonant acoustic media using soft-lithography techniques with elastomers. PMID- 22779567 TI - A model for spatial coherence from directive ambient noise in attenuating, dispersive media. AB - As a complement to experimental efforts in seismics and acoustics to infer geo acoustic properties of the propagation environment from the second order statistics of ambient noise measurements, a set of exact, explicit, closed form expressions for the cross-spectral density and spatial coherence of diffuse random wave fields is presented. Taken together, the expressions are well suited for modeling broadband, diffuse wave coherence in realistic scenarios involving directive, ambient noise from local (i.e., volume) and distant (i.e., plane wave) source features in an open, dispersive, attenuating medium. PMID- 22779500 TI - Passive imaging with pulsed ultrasound insonations. AB - Previously, passive cavitation imaging has been described in the context of continuous-wave high-intensity focused ultrasound thermal ablation. However, the technique has potential use as a feedback mechanism for pulsed-wave therapies, such as ultrasound-mediated drug delivery. In this paper, results of experiments and simulations are reported to demonstrate the feasibility of passive cavitation imaging using pulsed ultrasound insonations and how the images depend on pulsed ultrasound parameters. The passive cavitation images were formed from channel data that was beamformed in the frequency domain. Experiments were performed in an invitro flow phantom with an experimental echo contrast agent, echogenic liposomes, as cavitation nuclei. It was found that the pulse duration and envelope have minimal impact on the image resolution achieved. The passive cavitation image amplitude scales linearly with the cavitation emission energy. Cavitation images for both stable and inertial cavitation can be obtained from the same received data set. PMID- 22779568 TI - Dual mechanisms in the perceptual processing of click train temporal regularity. AB - Two experiments measured human sensitivity to temporal jitter in 25-click trains with inter-click intervals (ICIs) between 5 and 100 ms. In a naturalistic experiment using wideband clicks, jitter thresholds were a nonmonotonic function of ICI, peaking for ICIs near 40-60 ms. In a subsequent experiment, clicks were high-passed and presented against a low-frequency noise masker. Jitter threshold vs ICI functions lost the positive slope over short ICIs but retained the negative slope at long ICIs. The same behavior was seen in click rate discrimination tasks. Different processes mediate regularity analysis for click trains with ICIs above and below 40-60 ms. PMID- 22779569 TI - Single-channel dereverberation using a non-causal minimum variance distortionless response filter. AB - This letter presents a single-channel speech dereverberation approach using a non causal minimum variance distortionless response (MVDR) filter. The non-causal filter is adopted to utilize the additional information of the desired signal that lies in subsequent frames. Note that the desired signal output has minimal distortion due to the introduction of the MVDR criterion. The proposed system further suppresses the late reverberation by employing a statistical reverberant model. Experimental results demonstrate the superiority of the proposed algorithm to conventional approaches. PMID- 22779570 TI - Vibro-acoustic response of an infinite, rib-stiffened, thick-plate assembly using finite-element analysis. AB - The vibration of and sound radiation from an infinite, fluid-loaded, thick-plate assembly stiffened periodically with ribs are investigated numerically using finite-element analysis. First, numerical simulations are compared to the analytical solutions presented recently for this particular problem [Hull and Welch, J. Sound Vib. 329, 4192-4211 (2010)]. It is shown that the solutions reported in this reference are partially incorrect because the number of modes was not chosen correctly. Subsequently, the numerical model is used to study the effect of repeated and equally spaced void inclusions on the vibro-acoustic response of the system. PMID- 22779571 TI - Stress-dependent changes in the diffuse ultrasonic backscatter coefficient in steel: experimental results. AB - In this article, the effects of uniaxial compressive loading on the ultrasonic scattering from polycrystalline grains are shown for 10 MHz ultrasound in annealed, 1018 steel. The results show a decreasing value of the stress-dependent backscatter coefficient for normal incident ultrasound when the compression loading is perpendicular to the scattering direction. The change due to scattering is about 2 orders of magnitude greater than changes observed by others using ultrasonic wavespeed measurements. It is anticipated that this research can serve as the basis for many methods associated with nondestructive determination of stress in structural materials. PMID- 22779572 TI - Long-range time reversal communication in deep water: experimental results. AB - In December 2011 a long-range acoustic communication experiment was conducted in deep water, west of Izu-Ogasawara Islands, Japan. The experiment involved a stationary source (450-550 Hz) and an 18-element vertical array (102-m aperture), both deployed at around the sound channel axis. Initial analysis of data demonstrates that a data rate of 400 bits/s can be achieved over ~600-km range in deep water using 16 quadrature amplitude modulation and passive time reversal equalization. PMID- 22779573 TI - Comparative investigation of elastic properties in a trabecula using micro Brillouin scattering and scanning acoustic microscopy. AB - Micro-Brillouin scattering (MU-BR) and a 200 MHz scanning acoustic microscope (SAM) with similar spatial resolutions were applied to evaluate tissue elastic properties in two directions in a trabecula. Acoustic impedance measured by SAM was in the range of 5-9 Mrayl. Wave velocities determined by MU-BR were in the range of (4.75-5.11) * 10(3) m/s. Both exhibited a similar trend of variation across the trabecula and were significantly correlated (R(2) = 0.63-0.67, p < 0.01). MU-BR is useful for the evaluation of tissue stiffness within a trabecula. Combined with SAM or nanoindentation, it can provide additional information to assess elastic anisotropy at the micro-scale. PMID- 22779574 TI - How the cross-sectional discontinuity between ear canal and probe affects the ear canal length estimation. AB - Many ear canal probes both deliver and measure sound via narrow tubes. This study investigates the effect of the cross-sectional discontinuity at the interface between ear canal models and the connecting tubes of a commercially available otoacoustic emission probe on the "acoustically" estimated cavity lengths. Rigid cavities having the same length but different diameters were produced, and modeled by the finite element method. Cavities with a diameter larger than 8 mm had acoustic lengths that considerably overestimated the real geometry. A length correction was derived, which, in most applications, compensates for the measurement errors emerging from the discontinuity effects. PMID- 22779575 TI - Pulay forces from localized orbitals optimized in situ using a psinc basis set. AB - In situ optimization of a set of localized orbitals with respect to a systematically improvable basis set independent of the position of the atoms, such as psinc functions, would theoretically eliminate the correction due to Pulay forces from the total ionic forces. We demonstrate that for strict localization constraints, especially with small localization regions, there can be non-negligible Pulay forces that must be calculated as a correction to the Hellmann-Feynman forces in the ground state. Geometry optimization calculations, which rely heavily upon accurate evaluation of the total ionic forces, show much better convergence when Pulay forces are included. The more conventional case, where the local orbitals remain fixed to pseudo-atomic orbital multiple-zeta basis sets, also benefits from this implementation. We have validated the method on several test cases, including a DNA fragment with 1045 atoms. PMID- 22779576 TI - Umbrella integration with higher-order correction terms. AB - Umbrella integration is a method to analyze umbrella sampling simulations. It calculates free-energy changes from distributions obtained from molecular dynamics. While it can be formulated on the full sampled distributions, they are generally approximated by normal distributions. This is equivalent to the truncation of a power series of the free energy with respect to the reaction coordinate after the quadratic term or by a truncation of a cumulant expansion. Here, expressions for additional terms in the power series are derived. They can be calculated from the central moments of the distributions. This extension allows to test the approximations in applications. PMID- 22779577 TI - Steered transition path sampling. AB - We introduce a path sampling method for obtaining statistical properties of an arbitrary stochastic dynamics. The method works by decomposing a trajectory in time, estimating the probability of satisfying a progress constraint, modifying the dynamics based on that probability, and then reweighting to calculate averages. Because the progress constraint can be formulated in terms of occurrences of events within time intervals, the method is particularly well suited for controlling the sampling of currents of dynamic events. We demonstrate the method for calculating transition probabilities in barrier crossing problems and survival probabilities in strongly diffusive systems with absorbing states, which are difficult to treat by shooting. We discuss the relation of the algorithm to other methods. PMID- 22779578 TI - Near-field for electrodynamics at sub-wavelength scales: generalizing to an arbitrary number of dielectrics. AB - We extend the recently developed near-field (NF) method to include an arbitrary number of dielectrics. NF assumes that the dipoles and fields respond instantaneously to the density, without retardation. The central task in NF is the solution of the Poisson equation for every time step, which is here done by a conjugate gradient method which handles any dielectric distribution. The optical response of any metal-dielectric system can now be studied very efficiently in the near field region. The improved NF method is first applied to simple benchmark systems: a gold nanoparticle in vacuum and embedded in silica. The surface plasmons in these systems and their dependence on the dielectrics are reproduced in the new NF approach. As a further application, we study a silver nanoparticle-based structure for the optical detection of a "lipid" (i.e., dielectric) layer in water, where the layer is wrapping around part of the metallic nanostructure. We show the ~0.1-0.15 eV shift in the spectrum due to the presence of the layer, for both spherical and non-spherical (sphere+rod) systems with various polarizations. PMID- 22779579 TI - Fast time-reversible algorithms for molecular dynamics of rigid-body systems. AB - In this paper, we present time-reversible simulation algorithms for rigid bodies in the quaternion representation. By advancing a time-reversible algorithm [Y. Kajima, M. Hiyama, S. Ogata, and T. Tamura, J. Phys. Soc. Jpn. 80, 114002 (2011)] that requires iterations in calculating the angular velocity at each time step, we propose two kinds of iteration-free fast time-reversible algorithms. They are easily implemented in codes. The codes are compared with that of existing algorithms through demonstrative simulation of a nanometer-sized water droplet to find their stability of the total energy and computation speeds. PMID- 22779580 TI - Monte Carlo simulation based on dynamic disorder model in organic semiconductors: from coherent to incoherent transport. AB - The dynamic disorder model for charge carrier transport in organic semiconductors has been extensively studied in recent years. Although it is successful on determining the value of bandlike mobility in the organic crystalline materials, the incoherent hopping, the typical transport characteristic in amorphous molecular semiconductors, cannot be described. In this work, the decoherence process is taken into account via a phenomenological parameter, say, decoherence time, and the projective and Monte Carlo method are applied for this model to determine the waiting time and thus the diffusion coefficient. It is obtained that the type of transport is changed from coherent to incoherent with a sufficiently short decoherence time, which indicates the essential role of decoherence time in determining the type of transport in organics. We have also discussed the spatial extent of carriers for different decoherence time, and the transition from delocalization (carrier resides in about 10 molecules) to localization is observed. Based on the experimental results of spatial extent, we estimate that the decoherence time in pentacene has the order of 1 ps. Furthermore, the dependence of diffusion coefficient on decoherence time is also investigated, and corresponding experiments are discussed. PMID- 22779581 TI - A parameter-free, solid-angle based, nearest-neighbor algorithm. AB - We propose a parameter-free algorithm for the identification of nearest neighbors. The algorithm is very easy to use and has a number of advantages over existing algorithms to identify nearest-neighbors. This solid-angle based nearest neighbor algorithm (SANN) attributes to each possible neighbor a solid angle and determines the cutoff radius by the requirement that the sum of the solid angles is 4pi. The algorithm can be used to analyze 3D images, both from experiments as well as theory, and as the algorithm has a low computational cost, it can also be used "on the fly" in simulations. In this paper, we describe the SANN algorithm, discuss its properties, and compare it to both a fixed-distance cutoff algorithm and to a Voronoi construction by analyzing its behavior in bulk phases of systems of carbon atoms, Lennard-Jones particles and hard spheres as well as in Lennard Jones systems with liquid-crystal and liquid-vapor interfaces. PMID- 22779582 TI - A probability generating function method for stochastic reaction networks. AB - In this paper we present a probability generating function (PGF) approach for analyzing stochastic reaction networks. The master equation of the network can be converted to a partial differential equation for PGF. Using power series expansion of PGF and Pade approximation, we develop numerical schemes for finding probability distributions as well as first and second moments. We show numerical accuracy of the method by simulating chemical reaction examples such as a binding unbinding reaction, an enzyme-substrate model, Goldbeter-Koshland ultrasensitive switch model, and G(2)/M transition model. PMID- 22779584 TI - Equation-of-motion coupled-cluster method for the study of shape resonance. AB - The equation-of-motion coupled-cluster method (EOM-CC) is applied for the first time to calculate the energy and width of a shape resonance in an electron molecule scattering. The procedure is based on inclusion of complex absorbing potential with EOM-CC theory. We have applied this method to investigate the shape resonance in e(-)N(2), e(-)CO, and e(-)C(2)H(2). PMID- 22779583 TI - Size-extensive vibrational self-consistent field methods with anharmonic geometry corrections. AB - In the size-extensive vibrational self-consistent field (XVSCF) method introduced earlier [M. Keceli and S. Hirata, J. Chem. Phys. 135, 134108 (2011)], only a small subset of even-order force constants that can form connected diagrams were used to compute extensive total energies and intensive transition frequencies. The mean-field potentials of XVSCF formed with these force constants have been shown to be effectively harmonic, making basis functions, quadrature, or matrix diagonalization in the conventional VSCF method unnecessary. We introduce two size-consistent VSCF methods, XVSCF(n) and XVSCF[n], for vibrationally averaged geometries in addition to energies and frequencies including anharmonic effects caused by up to the nth-order force constants. The methods are based on our observations that a small number of odd-order force constants of certain types can form open, connected diagrams isomorphic to the diagram of the mean-field potential gradients and that these nonzero gradients shift the potential minima by intensive amounts, which are interpreted as anharmonic geometry corrections. XVSCF(n) evaluates these mean-field gradients and force constants at the equilibrium geometry and estimates this shift accurately, but approximately, neglecting the coupling between these two quantities. XVSCF[n] solves the coupled equations for geometry corrections and frequencies with an iterative algorithm, giving results that should be identical to those of VSCF when applied to an infinite system. We present the diagrammatic and algebraic definitions, algorithms, and initial implementations as well as numerical results of these two methods. The results show that XVSCF(n) and XVSCF[n] reproduce the vibrationally averaged geometries of VSCF for naphthalene and anthracene in their ground and excited vibrational states accurately at fractions of the computational cost. PMID- 22779585 TI - Transferable pair potentials for CdS and ZnS crystals. AB - A set of interatomic pair potentials is developed for CdS and ZnS crystals. We show that a simple energy function, which has been used to describe the properties of CdSe [E. Rabani, J. Chem. Phys. 116, 258 (2002)], can be parametrized to accurately describe the lattice and elastic constants, and phonon dispersion relations of bulk CdS and ZnS in the wurtzite and rocksalt crystal structures. The predicted coexistence pressure of the wurtzite and rocksalt structures as well as the equation of state are in good agreement with experimental observations. These new pair potentials enable the study of a wide range of processes in bulk and nanocrystalline II-VI semiconductor materials. PMID- 22779586 TI - Numeric kinetic energy operators for molecules in polyspherical coordinates. AB - Generalized curvilinear coordinates, as, e.g., polyspherical coordinates, are in general better adapted to the resolution of the nuclear Schrodinger equation than rectilinear ones like the normal mode coordinates. However, analytical expressions of the kinetic energy operators (KEOs) for molecular systems in polyspherical coordinates may be prohibitively complicated for large systems. In this paper we propose a method to generate a KEO numerically and bring it to a form practicable for dynamical calculations. To examine the new method we calculated vibrational spectra and eigenenergies for nitrous acid (HONO) and compare it with results obtained with an exact analytical KEO derived previously [F. Richter, P. Rosmus, F. Gatti, and H.-D. Meyer, J. Chem. Phys. 120, 6072 (2004)]. In a second example we calculated pi -> pi* photoabsorption spectrum and eigenenergies of ethene (C(2)H(4)) and compared it with previous work [M. R. Brill, F. Gatti, D. Lauvergnat, and H.-D. Meyer, Chem. Phys. 338, 186 (2007)]. In this ethene study the dimensionality was reduced from 12 to 6 by freezing six internal coordinates. Results for both molecules show that the proposed method for obtaining an approximate KEO is reliable for dynamical calculations. The error in eigenenergies was found to be below 1 cm(-1) for most states calculated. PMID- 22779587 TI - Computational determination of the A state absorption spectrum of NH3 and of ND3 using a new quasi-diabatic representation of the X and A states and full six dimensional quantum dynamics. AB - A recently developed method to represent adiabatic electronic states coupled by conical intersections has been used to construct a full six-dimensional quasi diabatic representation of the 1(1)A and 2(1)A states of NH(3). This representation is expected to be appropriate to simulate the photodissociation of ammonia when it is excited to the 2(1)A electronic state. In this work, the electronic structure aspects of this quasi-diabatic representation are analyzed. This representation is then used as the basis for a simulation of the A <- X absorption spectrum, dominated by a progression in the v(2) mode, using a full six-dimensional quantum mechanical treatment of the nuclear motion. Results are reported for both NH(3) and ND(3). This simulation provides the most accurate computational determination of this absorption spectrum reported to date. These results serve to validate the quasi-diabatic representation and set the stage for subsequent studies of vibrationally mediated photodissociation of NH(3). PMID- 22779588 TI - Non-adiabatic transitions from I2(E0g+ and D0u+) states induced by collisions with M = I2(X0g+) and H2O. AB - The stepwise two-step two-color and three-step three-color laser excitation schemes are used for selective population of rovibronic levels of the first-tier ion-pair E0(g)(+) and D0(u)(+) states of molecular iodine and studies of non adiabatic transitions to the D and E states induced by collisions with M = I(2)(X) and H(2)O. Collection and analysis of the luminescence after excitation of the v(E) = 8, 13 and v(D) = 13, 18 vibronic levels of the E and D states in the pure iodine vapor and the gas-phase mixtures with H(2)O provide rate constants for the non-adiabatic transitions to the D and E state induced by collisions with these molecules. Vibrational distributions for the [formula: see text] collision-induced non-adiabatic transitions (CINATs) are obtained. Rather strong lambda(lum)(max) ~ 3400 A luminescence band is observed in the I(2) + H(2)O mixtures, whereas its intensity is ~100 times less in pure iodine vapor. Radiative lifetimes and quenching rate constants of the I(2)(E,v(E) = 8, 13 and D,v(D) = 13, 18) vibronic state are also determined. Rate constants of the [formula: see text], v(E) = 8-54, CINATs are measured again and compared with those obtained earlier. New data confirm resonance characters of the CINATs found in our laboratory about 10 years ago. Possible reasons of differences between rate constant values obtained in this and earlier works are discussed. It is shown, in particular, that differences in rate constants of non-resonant CINATs are due to admixture of water vapor in iodine. PMID- 22779589 TI - Insights on the CN B 2Sigma+ + Ar potential from ultraviolet fluorescence excitation and infrared depletion studies of the CN-Ar complex. AB - UV laser-induced fluorescence and IR-UV fluorescence depletion studies have been used to characterize the intermolecular levels of the CN-Ar complex in the excited state correlating with CN B (2)Sigma(+) + Ar. Additional CN-Ar features are identified to lower wavenumber than reported previously. Fluorescence depletion spectra are recorded to confirm that these CN-Ar features and other higher energy features in the B-X spectrum originate from a common ground state level. The UV depletion is induced by IR excitation of CN-Ar from the ground state zero-point level to a hindered internal rotor state (n(K) = 1(1)) in the CN overtone region. The lowest energy feature in the B-X spectrum at 25,714.1 cm(-1) is assigned as a transition to the zero-point level of the B state and also yields its binding energy, D(0) = 186(2) cm(-1), which is in excellent accord with theoretical predictions. The next feature approximately 40 cm(-1) higher is attributed to overlapping transitions to intermolecular levels with bend (v(b)(K)=1(1)) or stretch (v(s) = 1) excitation. Yet higher features (previously reported) are also assigned, based on their transition type and wavenumber, which are consistent with the intermolecular energy level pattern computed theoretically. Finally, the intensity profile of the lowest energy features in the B-X spectrum reflects the predicted change in the CN (B (2)Sigma(+), X (2)Sigma(+)) + Ar potentials upon electronic excitation from a weakly anisotropic potential about the linear N=C-Ar configuration in the ground state to a more strongly bound linear C=N-Ar structure in the excited B electronic state. PMID- 22779590 TI - Experimental characterization of the CN X 2Sigma+ + Ar and H2 potentials via infrared-ultraviolet double resonance spectroscopy. AB - The hindered internal rotor states (n(K) = 0(0), 1(1), and 1(0)) of the CN-Ar complex with two quanta of CN stretch (v(CN) = 2), along with its ground state (v(CN) = 0), have been characterized by IR-UV double resonance and UV spectroscopy. Analysis of rotationally structured bands enable n(K) assignments and reveal perturbations due to Coriolis coupling between two closely spaced hindered rotor states, n(K) = 1(1) and 1(0). A deperturbation analysis is carried out to derive accurate rotational constants and their associated CN center-of mass to Ar bond lengths as well as the magnitude of the coupling. The energetic ordering and spacings of the CN-Ar hindered rotor states provide a direct experimental probe of the angular dependence of the CN X (2)Sigma(+) + Ar potential and permit radially averaged anisotropy parameters (V(10) = 5.2 cm(-1) and V(20) = 3.2 cm(-1)) to be determined. This analysis indicates a relatively flat potential about a linear N=C-Ar configuration with a barrier to CN internal rotation of only ~12 cm(-1). The angular potentials determined from experiment and ab initio theory are in good accord, although theory predicts a higher barrier to CN internal rotation. A similar approach yields the infrared spectrum of H(2)-CN in the CN overtone region, which exhibits a rotationally resolved Sigma <- Sigma parallel band that is consistent with theoretical predictions for ortho-H(2)-CN. PMID- 22779591 TI - Product branching ratios in photodissociation of phenyl radical: a theoretical ab initio/Rice-Ramsperger-Kassel-Marcus study. AB - Ab initio CCSD(T)/CBS//B3LYP/6-311G** calculations of the potential energy surface for possible dissociation channels of the phenyl radical are combined with microcanonical Rice-Ramsperger-Kassel-Marcus calculations of reaction rate constants in order to predict statistical product branching ratios in photodissociation of c-C(6)H(5) at various wavelengths. The results indicate that at 248 nm the photodissociation process is dominated by the production of ortho benzyne via direct elimination of a hydrogen atom from the phenyl radical. At 193 nm, the statistical branching ratios are computed to be 63.4%, 21.1%, and 14.4% for the o-C(6)H(4) + H, l-C(6)H(4) ((Z)-hexa-3-ene-1,5-diyne) + H, and n-C(4)H(3) + C(2)H(2) products, respectively, in a contradiction with recent experimental measurements, which showed C(4)H(3) + C(2)H(2) as the major product. Although two lower energy pathways to the i-C(4)H(3) + C(2)H(2) products are identified, they appeared to be kinetically unfavorable and the computed statistical branching ratio of i-C(4)H(3) + C(2)H(2) does not exceed 1%. To explain the disagreement with experiment, we optimized conical intersections between the ground and the first excited electronic states of C(6)H(5) and, based on their structures and energies, suggested the following photodissociation mechanism at 193 nm: c C(6)H(5) 1 -> absorption of a photon -> electronically excited 1 -> internal conversion to the lowest excited state -> conversion to the ground electronic state via conical intersections at CI-2 or CI-3 -> non-statistical decay of the vibrationally excited radical favoring the formation of the n-C(4)H(3) + C(2)H(2) products. This scenario can be attained if the intramolecular vibrational redistribution in the CI-2 or CI-3 structures in the ground electronic state is slower than their dissociation to n-C(4)H(3) + C(2)H(2) driven by the dynamical preference. PMID- 22779592 TI - A theoretical study on structures, energetics, and spectra of Br-.nCO2 clusters: towards bridging the gap between micro-domain and macro-domain. AB - Structures, energetics, and spectra of Br(-).nCO(2) (n = 1-8) clusters are studied based on ab initio electronic structure theory. The geometry of each size of clusters is evaluated by employing second-order Moller-Plesset (MP2) perturbation theory. It is observed that the solvent CO(2) molecules approach the bromide moiety from one side in an asymmetric fashion except for the Br(-).8CO(2) cluster. Simple electrostatic model for charge-quadrupole interactions is valid for the Br(-).nCO(2) clusters. Reduced variational space based energy decomposition method shows that the electrostatic interaction is the major component and polarization and charge transfer energies are the other significant components of the total interaction energy. Both adiabatic and vertical electron detachment energies and solvation energies are calculated at MP2 level of theory. We have observed an excellent agreement between theory and experiment for the vertical detachment and solvation energies. Calculated quantities based on the analytical expression which connects the finite domain to macroscopic one are found to be very good in agreement with the available experimental results. The present study reveals a 2.6 eV increase in the detachment energy of bromide anion due to the solvation effect of CO(2), which is relatively small compared to that of the corresponding 4.7 eV increase in detachment energy in water. PMID- 22779593 TI - Electron attachment to antipyretics: possible implications of their metabolic pathways. AB - The empty-level structures and formation of negative ion states via resonance attachment of low-energy (0-15 eV) electrons into vacant molecular orbitals in a series of non-steroidal anti-inflammatory drugs (NSAIDs), namely aspirin, paracetamol, phenacetin, and ibuprofen, were investigated in vacuo by electron transmission and dissociative electron attachment (DEA) spectroscopies, with the aim to model the behavior of these antipyretic agents under reductive conditions in vivo. The experimental findings are interpreted with the support of density functional theory calculations. The negative and neutral fragments formed by DEA in the gas phase display similarities with the main metabolites of these commonly used NSAIDs generated in vivo by the action of cytochrome P450 enzymes, as well as with several known active agents. It is concluded that xenobiotic molecules which possess pronounced electron-accepting properties could in principle follow metabolic pathways which parallel the gas-phase dissociative decay channels observed in the DEA spectra at incident electron energies below 1 eV. Unwanted side effects as, e.g., hepatoxicity or carcinogenicity produced by the NSAIDs under study in human organism are discussed within the "free radical model" framework, reported earlier to describe the toxic action of the well-known model toxicant carbon tetrachloride. PMID- 22779594 TI - Sub-Doppler infrared spectroscopy of CH2D radical in a slit supersonic jet: isotopic symmetry breaking in the CH stretching manifold. AB - First high-resolution infrared absorption spectra in the fundamental symmetric/asymmetric CH stretching region of isotopically substituted methyl radical, CH(2)D, are reported and analyzed. These studies become feasible in the difference frequency spectrometer due to (i) high density radical generation via dissociative electron attachment to CH(2)DI in a discharge, (ii) low rotational temperatures (23 K) from supersonic cooling in a slit expansion, (iii) long absorption path length (64 cm) along the slit axes, and (iv) near shot noise limited absorption sensitivity (5 * 10(-7)/?(Hz)). The spectra are fully rovibrationally resolved and fit to an asymmetric top rotational Hamiltonian to yield rotational/centrifugal constants and vibrational band origins. In addition, the slit expansion collisionally quenches the transverse velocity distribution along the laser probe direction, yielding sub-Doppler resolution of spin-rotation structure and even partial resolution of nuclear hyperfine structure for each rovibrational line. Global least-squares fits to the line shapes provide additional information on spin-rotation and nuclear hyperfine constants, which complement and clarify previous FTIR studies [K. Kawaguchi, Can. J. Phys. 79, 449 (2001)] of CH(2)D in the out-of-plane bending region. Finally, analysis of the spectral data from the full isotopomeric CH(m)D(3-m) series based on harmonically coupled Morse oscillators establishes a predictive framework for describing the manifold of planar stretching vibrations in this fundamental combustion radical. PMID- 22779595 TI - Quartic force field predictions of the fundamental vibrational frequencies and spectroscopic constants of the cations HOCO+ and DOCO+. AB - Only one fundamental vibrational frequency of protonated carbon dioxide (HOCO(+)) has been experimentally observed in the gas phase: the nu(1) O-H stretch. Utilizing quartic force fields defined from CCSD(T)/aug-cc-pVXZ (X = T,Q,5) complete basis set limit extrapolated energies modified to include corrections for core correlation and scalar relativistic effects coupled to vibrational perturbation theory and vibrational configuration interaction computations, we are predicting the full set of gas phase fundamental vibrational frequencies of HOCO(+). Our prediction of nu(1) is within less than 1 cm(-1) of the experimental value. Our computations also include predictions of the gas phase fundamental vibrational frequencies of the deuterated form of the cation, DOCO(+). Additionally, other spectroscopic constants for both systems are reported as part of this study, and a search for a cis-HOCO(+) minimum found no such stationary point on the potential surface indicating that only the trans isomer is stable. PMID- 22779596 TI - VUV Fourier-transform absorption study of the Lyman and Werner bands in D2. AB - An extensive survey of the D(2) absorption spectrum has been performed with the high-resolution VUV Fourier-transform spectrometer employing synchrotron radiation. The frequency range of 90,000-119,000 cm(-1) covers the full depth of the potential wells of the B (1)Sigma(u)(+), B' (1)Sigma(u)(+), and C (1)Pi(u) electronic states up to the D(1s) + D(2l) dissociation limit. Improved level energies of rovibrational levels have been determined up to respectively v = 51, v = 13, and v = 20. Highest resolution is achieved by probing absorption in a molecular gas jet with slit geometry, as well as in a liquid helium cooled static gas cell, resulting in line widths of ~0.35 cm(-1). Extended calibration methods are employed to extract line positions of D(2) lines at absolute accuracies of 0.03 cm(-1). The D (1)Pi(u) and B'' (1)Sigma(u)(+) electronic states correlate with the D(1s) + D(3l]) dissociation limit, but support a few vibrational levels below the second dissociation limit, respectively, v = 0-3 and v = 0-1, and are also included in the presented study. The complete set of resulting level energies is the most comprehensive and accurate data set for D(2). The observations are compared with previous studies, both experimental and theoretical. PMID- 22779597 TI - Electron correlation effects on the electric properties of fluorinated polyacetylene. AB - Using the Hartree-Fock (HF) and second-order Moller-Plesset perturbation theory (MP2) methods with the 6-31G(d) basis set, we have investigated the chain length dependence of the longitudinal dipole moment and longitudinal components of the static linear polarizability, first and second hyperpolarizabilities of fluorinated polyacetylene chains. It is found that geometry changes caused by the electron correlation (EC) effects imply in marked increases of the electric properties but to obtain a reliable description it is necessary to properly account for both geometric and electronic changes. Based on the fast convergence pattern presented by the MP2/HF ratios and from the converged HF oligomeric results, we have estimated the MP2 electric properties of long chains. The asymptotic value for the MP2 second hyperpolarizability per unit cell is estimated in 1.9 * 10(8) a.u. This result is one order of magnitude larger than the corresponding result reported for the unsubstituted polyacetylene chains. PMID- 22779598 TI - Structures of small mixed krypton-xenon clusters. AB - Structures of small mixed krypton-xenon clusters of different compositions with an average size of 30-37 atoms are investigated. The Kr 3d(5/2) and Xe 4d(5/2) surface core level shifts and photoelectron intensities originating from corner, edge, and face/bulk sites are analyzed by using soft x-ray photoelectron spectroscopy. Structural models are derived from these experiments, which are confirmed by theoretical simulation taking induced dipole interactions into account. It is found that one or two small Xe cores are partly embedded in the surface of the Kr clusters. These may grow and merge leading to a phase separation between the two rare gas moieties in mixed clusters with increasing the Xe content. PMID- 22779599 TI - A three-state effective Hamiltonian for symmetric cationic diarylmethanes. AB - We analyze the low-energy electronic structure of a series of symmetric cationic diarylmethanes, which are bridge-substituted derivatives of Michler's Hydrol Blue. We use a four-electron, three-orbital complete active space self-consistent field and multi-state multi-reference perturbation theory model to calculate a three-state diabatic effective Hamiltonian for each dye in the series. We exploit an isolobal analogy between the active spaces of the self-consistent field solutions for each dye to represent the electronic structure in a set of analogous diabatic states. The diabatic states can be identified with the bonding structures in classical resonance-theoretic models of cyanine dyes. We identify diabatic states with opposing charge and bond-order localization, analogous to the classical resonance structures, and a third state with charge on the bridge. While the left- and right-charged structures are similar for all dyes, the structure of the bridge-charged diabatic state, and the Hamiltonian matrix elements connected to it, change significantly across the series. The change is correlated with an inversion of the sign of the charge carrier on the bridge, which changes from an electron pair to a hole as the series is traversed. PMID- 22779600 TI - A witness for coherent electronic vs vibronic-only oscillations in ultrafast spectroscopy. AB - We report a conceptually straightforward witness that distinguishes coherent electronic oscillations from their vibronic-only counterparts in nonlinear optical spectra of molecular aggregates. Coherent oscillations as a function of waiting time in broadband pump/broadband probe spectra correspond to coherent electronic oscillations in the singly excited manifold. Oscillations in individual peaks of 2D electronic spectra do not necessarily yield this conclusion. Our witness is simpler to implement than quantum process tomography and potentially resolves a long-standing controversy on the character of oscillations in ultrafast spectra of photosynthetic light harvesting systems. PMID- 22779601 TI - Statistical description of hydrodynamic processes in ionic melts while taking into account polarization effects. AB - A statistical description of hydrodynamic processes for molten salts is proposed taking into account polarization effects caused by the deformation of external ionic shells. This description is conducted by means of the Zubarev nonequilibrium statistical operator method, appropriate for researches of both strong and weak nonequilibrium processes. The nonequilibrium statistical operator and the generalized hydrodynamic equations that take into account the polarization processes are acquired for the ion-polarization model of ionic molten salts when the nonequilibrium averaged values of densities of ions number, their momentum, dipole momentum, and total energy are chosen for the reduced description parameters. A spectrum of collective excitations is investigated within the viscoelastic approximation for the ion-polarization model of ionic melts. PMID- 22779602 TI - Isotropic-nematic phase transition in the Lebwohl-Lasher model from density of states simulations. AB - Density of states Monte Carlo simulations have been performed to study the isotropic-nematic (IN) transition of the Lebwohl-Lasher model for liquid crystals. The IN transition temperature was calculated as a function of system size using expanded ensemble density of states simulations with histogram reweighting. The IN temperature for infinite system size was obtained by extrapolation of three independent measures. A subsequent analysis of the kinetics in the model showed that the transition occurs via spinodal decomposition through aggregation of clusters of liquid crystal molecules. PMID- 22779603 TI - Rapid hydrogen hydrate growth from non-stoichiometric tuning mixtures during liquid nitrogen quenching. AB - In this study the rapid growth of sII H(2) hydrate within 20 min of post formation quenching towards liquid nitrogen (LN(2)) temperature is presented. Initially at 72 MPa and 258 K, hydrate samples would cool to the conditions of ~60 MPa and ~90 K after quenching. Although within the stability region for H(2) hydrate, new hydrate growth only occurred under LN(2) quenching of the samples when preformed hydrate "seeds" of THF + H(2) were in the presence of unconverted ice. The characterization of hydrate seeds and the post-quenched samples was performed with confocal Raman spectroscopy. These results suggest that quenching to LN(2) temperature, a common preservation technique for ex situ hydrate analysis, can lead to rapid unintended hydrate growth. Specifically, guest such as H(2) that may otherwise need sufficiently long induction periods to nucleate, may still experience rapid growth through an increased kinetic effect from a preformed hydrate template. PMID- 22779604 TI - Molecular dynamics simulations of a hard sphere crystal and reaction-like mechanism for homogeneous melting. AB - Molecular dynamics simulations of a hard sphere crystal are performed for volume fractions ranging from solidification point to melting point. A local bond order parameter is chosen to assign a nature, liquid or solid, to a particle. The probability for a liquid or solid particle to change state presents a typical sigmoid shape as the nature of its neighbors changes. Using this property, I propose a reaction-like mechanism and introduce a small number of rate constants. A mean-field approach to melting and a kinetic Monte Carlo algorithm on a lattice are derived from these chemical processes. The results of these models successfully compare with molecular dynamics simulations, proving that the main properties of melting can be captured by a small number of dynamical parameters. PMID- 22779605 TI - Controlling activated processes of nonadiabatically, periodically driven dynamical systems: a multiple scale perturbation approach. AB - We arrive at the escape rate from a metastable state for a system of Brownian particles driven periodically by a space dependent, rapidly oscillating external perturbation (with frequency omega) in one dimension (one of the most important class of nonequilibrium system). Though the problem may seem to be time dependent, and is poised on the extreme opposite side of adiabaticity, there exists a multiple scale perturbation theory ("Kapitza window") by means of which the dynamics can be treated in terms of an effective time-independent potential that is derived as an expansion in orders of 1/omega to the order omega(-3). The resulting time-independent equation is then used to calculate the escape rate of physical systems from a metastable state induced by external monochromatic field in the moderate-to-large damping limit and to investigate the effect of omega on the resulting rate in conjunction with the thermal energy. With large value of omega, we find that the environment with moderate-to-large damping impedes the escape process of the particle while high amplitude of the periodic driving force allows the particle to cross the barrier with a large escape rate. A comparison of our theoretical expression with numerical simulation gives a satisfactory agreement. PMID- 22779606 TI - Molecular dynamics with quantum transitions study of the vibrational relaxation of the HOD bend fundamental in liquid D2O. AB - The molecular dynamics with quantum transitions method is used to study the vibrational relaxation of the HOD bend fundamental in liquid D(2)O. All of the vibrational bending degrees of freedom of the HOD and D(2)O molecules are described by quantum mechanics, while the remaining translational and rotational degrees of freedom are described classically. The effect of the coupling between the rotational and vibrational degrees of freedom of the deuterated water molecules is analyzed. A kinetic mechanism based on three steps is proposed in order to interpret the dynamics of the system. It is shown that intermolecular vibrational energy transfer plays an important role in the relaxation process and also that the transfer of energy into the rotational degrees of freedom is favored over the transfer of energy into the translational motions. The thermalization of the system after the relaxation is reached in a shorter time scale than that of the recovery of the hydrogen bond network. The relaxation and equilibration times obtained compare well with experimental and previous theoretical results. PMID- 22779607 TI - Raman spectroscopy of optically levitated supercooled water droplet. AB - By use of an optical trap, we can levitate micrometer-sized drops of purified water and cool them below the melting point free from contact freezing. Raman spectra of the OH stretching band were obtained from those supercooled water droplets at temperatures down to -35 degrees C. According to the two-state model, an enthalpy change due to hydrogen-bond breaking is derived from temperature dependence of the spectral profile. The isobaric heat capacity calculated from the enthalpy data shows a sharp increase as the temperature is lowered below -20 degrees C in good agreement with conventional thermodynamic measurements. PMID- 22779608 TI - Study of dynamics and crystallization kinetics of 5-methyl-2-[(2 nitrophenyl)amino]-3-thiophenecarbonitrile at ambient and elevated pressure. AB - The organic liquid ROY, i.e., 5-methyl-2-[(2-nitrophenyl)amino]-3 thiophenecarbonitrile, has been a subject of detailed study in the last few years. One interest in ROY lies in its polymorph-dependent fast crystal growth mode below and above the glass transition temperature. This growth mode is not diffusion controlled, and the possibility that it is enabled by secondary relaxation had been suggested. However, a previous study by dielectric relaxation spectroscopy had not been able to find any resolved secondary relaxation. The present paper reports new dielectric measurements of ROY in the liquid and glassy states at ambient pressure and elevated pressure, which were performed to provide more insight into the molecular dynamics as well as the crystallization tendency of ROY. In the search of secondary relaxation, a special glassy state of ROY was prepared by applying high pressure to the liquid state, from which secondary relaxation was possibly resolved. Thus, the role of secondary relaxation in crystallization of ROY remains to be clarified. Notwithstanding, the secondary relaxation present is not necessarily the sole enabler of crystallization. In an effort to search for possible cause of crystallization other than secondary relaxation, we also performed crystallization kinetics studies of ROY at different T and P combinations while keeping the structural relaxation time constant. The results show that crystallization of ROY speeds up with pressure, opposite to the trend found in the crystallization of ibuprofen studied up to 1 GPa. The dielectric relaxation and thermodynamic properties of ROY with phenolphthalein dimethylether (PDE) are similar in many respects, but PDE does not crystallize. Taking all the above into account, besides the secondary relaxation, the specific chemical structure, molecular interactions and packing of the molecules are additional factors that could affect the kinetics of crystallization found in ROY. PMID- 22779609 TI - A molecular simulation study on the role of ion sizes and dielectric images in near-surface ion distribution far from the strong coupling limit. AB - A series of Monte Carlo simulations of the planar electric double layers are carried out in the primitive model for two electrolyte mixtures next to a smooth and uniformly charged hard wall representing an ideal biological interface with low and moderate surface charge densities. The structural information of the double layers is applied to reveal charge inversion and overcharging through the addition of multivalent electrolyte at a certain physiological concentration. Various values for the radius of the ions are taken into account to capture the impact of short-range correlations. Meanwhile, the influence of image charges on ion distribution is analyzed, which stems from dielectric discontinuity between the interior and exterior of the membrane matrix. It is clearly shown that depending on the amount of foreign salt, the large size of charged species regardless of its polarity plays a positive role in promoting charge inversion. Moreover, our findings indicate that charge inversion do not signify the reversal of the electrophoretic mobility, in consistent with the recent theoretical predictions by Horno and co-workers [J. Colloid Interface Sci. 356, 325 (2011)]. In addition, the depletion effect triggered by repulsive image forces which are intertwined with the excluded volume correlations gives rise to an anomalous overcharging for low surface charged surface in the high concentrations of trivalent salt. Overall, the ion distribution in a double layer is exclusively governed by entropic and electrostatic contributions but with preferentially leading status for different magnitudes of surface charge. PMID- 22779610 TI - Stability and migration of large oxygen clusters in UO(2+x): density functional theory calculations. AB - Using ab initio molecular dynamics simulations and nudged elastic band calculations we examine the finite temperature stability, transition pathways, and migration mechanisms of large oxygen clusters in UO(2+x). Here we specifically consider the recently proposed split quad-interstitial and cuboctahedral oxygen clusters. It is shown that isolated cuboctahedral clusters may transform into more stable configurations that are closely linked to the split quad-interstitial. The split quad-interstitial is stable with respect to single interstitials occupying the empty octahedral holes of the UO(2) lattice. In order to better understand discrepancies between theory and experiments, the simulated atomic pair distribution functions for the split quad-interstitial structures are analyzed with respect to the distribution function for U(4)O(9) previously obtained from neutron diffraction data. Our nudged elastic band calculations suggest that the split quad-interstitial may migrate by translating one of its constituent di-interstitial clusters via a barrier that is lower than the corresponding barrier for individual interstitials, but higher than the barrier for the most stable di-interstitial cluster. PMID- 22779611 TI - Pre-combustion CO2 capture by transition metal ions embedded in phthalocyanine sheets. AB - Transition metal (TM) embedded two-dimensional phthalocyanine (Pc) sheets have been recently synthesized in experiments [M. Abel, S. Clair, O. Ourdjini, M. Mossoyan, and L. Porte, J. Am. Chem. Soc. 133, 1203 (2010)], where the transition metal ions are uniformly distributed in porous structures, providing the possibility of capturing gas molecules. Using first principles and grand canonical Monte Carlo simulations, TMPc sheets (TM = Sc, Ti, and Fe) are studied for pre-combustion CO(2) capture by considering the adsorptions of H(2)/CO(2) gas mixtures. It is found that ScPc sheet shows a good selectivity for CO(2), and the excess uptake capacity of single-component CO(2) on ScPc sheet at 298 K and 50 bar is found to be 2949 mg/g, larger than that of any other reported porous materials. Furthermore, electrostatic potential and natural bond orbital analyses are performed to reveal the underlying interaction mechanisms, showing that electrostatic interactions as well as the donation and back donation of electrons between the transition metal ions and the CO(2) molecules play a key role in the capture. PMID- 22779612 TI - Substrate effect on the melting temperature of gold nanoparticles. AB - Previous experimental, molecular dynamics, and thermodynamic researches on the melting temperature of Au nanoparticles on tungsten substrate provide entirely different results. To account for the substrate effect upon the melting point of nanoparticles, three different substrates were tested by using a thermodynamic model: tungsten, amorphous carbon, and graphite. The results reveal that the melting point suppression of a substrate-supported Au nanoparticle is principally ruled by the free surface-to-volume ratio of the particle or the contact angle between the particle and the substrate. When the contact angle theta is less than 90 degrees , a stronger size-dependent melting point depression compared with those for free nanoparticles is predicted; when the contact angle theta is greater than 90 degrees , the melting temperature of the supported Au nanoparticles are somewhat higher than those for free nanoparticles. PMID- 22779613 TI - Charge regulation and local dielectric function in planar polyelectrolyte brushes. AB - Understanding the effect of inhomogeneity on the charge regulation and dielectric properties, and how it depends on the conformational characteristics of the macromolecules is a long-standing problem. In order to address this problem, we have developed a field-theory to study charge regulation and local dielectric function in planar polyelectrolyte brushes. The theory is used to study a polyacid brush, which is comprised of chains end-grafted at the solid-fluid interface, in equilibrium with a bulk solution containing monovalent salt ions, solvent molecules, and pH controlling acid. In particular, we focus on the effects of the concentration of added salt and pH of the bulk in determining the local charge and dielectric function. Our theoretical investigations reveal that the dipole moment of the ion-pairs formed as a result of counterion adsorption on the chain backbones play a key role in affecting the local dielectric function. For polyelectrolytes made of monomers having dipole moments lower than the solvent molecules, dielectric decrement is predicted inside the brush region. However, the formation of ion-pairs (due to adsorption of counterions coming from the dissociation of added salt) more polar than the solvent molecules is shown to increase the magnitude of the dielectric function with respect to its bulk value. Furthermore, an increase in the bulk salt concentration is shown to increase the local charge inside the brush region. PMID- 22779614 TI - Single species transport and self diffusion in wide single-walled carbon nanotubes. AB - We model and simulate gas flow through nanopores using a single-walled carbon nanotube model. Efficient protocols for the simulation of methane molecules in nanotubes are developed and validated for both the self-diffusivity, following a pulse perturbation, and for the transport diffusivity in an imposed concentration gradient. The former is found to be at least an order of magnitude lower than the latter, and to decline with increasing initial pressure, while the latter increases as the pressure gradient increases until it reaches an asymptotic value. Our previous analytic model, developed for single-file diffusion in narrow pores, is extended to wider pores for the case of single species transport. The model, which predicts the observed numerical results invokes four regimes of transport. The dominant transport is by ballistic motion near the wall in not too wide nanotubes when a pressure gradient or concentration is imposed; this mode is absent in the case of self-diffusion due to periodic boundary conditions. We also present results from systematic comparisons of flexible versus rigid tubes and explicit atom versus effective atomic potentials. PMID- 22779615 TI - Confinement and viscoelastic effects on chain closure dynamics. AB - Chemical reactions inside cells are typically subject to the effects both of the cell's confining surfaces and of the viscoelastic behavior of its contents. In this paper, we show how the outcome of one particular reaction of relevance to cellular biochemistry--the diffusion-limited cyclization of long chain polymers- is influenced by such confinement and crowding effects. More specifically, starting from the Rouse model of polymer dynamics, and invoking the Wilemski Fixman approximation, we determine the scaling relationship between the mean closure time t(c) of a flexible chain (no excluded volume or hydrodynamic interactions) and the length N of its contour under the following separate conditions: (a) confinement of the chain to a sphere of radius d and (b) modulation of its dynamics by colored Gaussian noise. Among other results, we find that in case (a) when d is much smaller than the size of the chain, t(c) ~ Nd(2), and that in case (b), t(c) ~ N(2/(2-2H)), H being a number between 1/2 and 1 that characterizes the decay of the noise correlations. H is not known a priori, but values of about 0.7 have been used in the successful characterization of protein conformational dynamics. At this value of H (selected for purposes of illustration), t(c) ~ N(3.4), the high scaling exponent reflecting the slow relaxation of the chain in a viscoelastic medium. PMID- 22779617 TI - A theoretical and simulation study of the self-assembly of a binary blend of diblock copolymers. AB - Pure diblock copolymer melts exhibit a narrow range of conditions at which bicontinuous and cocontinuous phases are stable; such conditions and the morphology of such phases can be tuned by the use of additives. In this work, we have studied a bidisperse system of diblock copolymers using theory and simulation. In particular, we elucidated how a short, lamellar-forming diblock copolymer modifies the phase behavior of a longer, cylinder-forming diblock copolymer. In a narrow range of intermediate compositions, self-consistent field theory predicts the formation of a gyroid phase although particle-based simulations show that three phases compete: the gyroid phase, a disordered cocontinuous phase, and the cylinder phase, all having free energies within error bars of each other. Former experimental studies of a similar system have yielded an unidentified, partially irregular bicontinuous phase, and our simulations suggest that at such conditions the formation of a partially transformed network phase is indeed plausible. Close examination of the spatial distribution of chains reveals that packing frustration (manifested by chain stretching and low density spots) occurs in the majority-block domains of the three competing phases simulated. In all cases, a double interface around the minority-block domains is also detected with the outer one formed by the short chains, and the inner one formed by the longer chains. PMID- 22779616 TI - Destruction of hydrogen bonds of poly(N-isopropylacrylamide) aqueous solution by trimethylamine N-oxide. AB - Trimethylamine N-oxide (TMAO) is a compatible or protective osmolyte that stabilizes the protein native structure through non-bonding mechanism between TMAO and hydration surface of protein. However, we have shown here first time the direct binding mechanism for naturally occurring osmolyte TMAO with hydration structure of poly(N-isopropylacrylamide) (PNIPAM), an isomer of polyleucine, and subsequent aggregation of PNIPAM. The influence of TMAO on lower critical solution temperature (LCST) of PNIPAM was investigated as a function of TMAO concentration at different temperatures by fluorescence spectroscopy, viscosity (eta), multi angle dynamic light scattering, zeta potential, and Fourier transform infrared (FTIR) spectroscopy measurements. To address some of the basis for further analysis of FTIR spectra of PNIPAM, we have also measured FTIR spectra for the monomer of N-isopropylacrylamide (NIPAM) in deuterium oxide (D(2)O) as a function of TMAO concentration. Our experimental results purportedly elucidate that the LCST values decrease with increasing TMAO concentration, which is mainly contributing to the direct hydrogen bonding of TMAO with the water molecules that are bound to the amide (-CONH) functional groups of the PNIPAM. We believed that the present work may act as a ladder to reach the heights of understanding of molecular mechanism between TMAO and macromolecule. PMID- 22779618 TI - Polymer induced changes of the crystallization scenario in suspensions of hard sphere like microgel particles. AB - We investigated the crystallization scenario of highly cross linked polystyrene particles dispersed in the good solvent 2-ethylnaphtalene and their mixtures with non-adsorbing low molecular weight polysterene polymer using time resolved static light scattering. The samples were prepared slightly below the melting volume fraction of the polymer free system. For the polymer free samples, we obtained polycrystalline solids via crystallization scenario known from hard sphere suspensions with little competition of wall crystal formation. Addition of non adsorbing low molecular weight polystyrene polymer leads to a considerably slowing down of the bulk crystallization kinetics. We observed a delay of the precursor to crystal conversion for the bulk crystallization while the induction times for the wall nucleation are reduced. The increased polymer concentration thus shifts the balance between the two competing crystallization pathways giving the possibility to tune the relative amount of wall based crystals. PMID- 22779619 TI - Effect of molybdenum on the structure formation of resorcinol-formaldehyde hydrogel studied by coherent x-ray scattering. AB - A detailed study on the effect of Mo on the gelation process of resorcinol formaldehyde systems is presented. The evolution of the system was followed by x ray photon correlation spectroscopy, which allows in situ investigation of the dynamics as well as of the structural evolution in non-equilibrium processes. The Mo was introduced into the system after a pre-polymerization period (PP), the effect of which was also examined. Our results show that the presence of Mo substantially modifies the gelation process by favoring the growth of large compact clusters with weak bonds between them. However, this effect can be reduced by increasing PP. PMID- 22779620 TI - Probing redox proteins on a gold surface by single molecule fluorescence spectroscopy. AB - The interaction between the fluorescently labeled redox protein, azurin, and a thin gold film is characterized using single-molecule fluorescence intensity and lifetime measurements. Fluorescence quenching starts at distances below 2.3 nm from the gold surface. At shorter distances the quantum yield may decrease down to fourfold for direct attachment of the protein to bare gold. Outside of the quenching range, up to fivefold enhancement of the fluorescence is observed on average with increasing roughness of the gold layer. Fluorescence-detected redox activity of individual azurin molecules, with a lifetime switching ratio of 0.4, is demonstrated for the first time close to a gold surface. PMID- 22779621 TI - Bistability in the chemical master equation for dual phosphorylation cycles. AB - Dual phospho/dephosphorylation cycles, as well as covalent enzymatic-catalyzed modifications of substrates are widely diffused within cellular systems and are crucial for the control of complex responses such as learning, memory, and cellular fate determination. Despite the large body of deterministic studies and the increasing work aimed at elucidating the effect of noise in such systems, some aspects remain unclear. Here we study the stationary distribution provided by the two-dimensional chemical master equation for a well-known model of a two step phospho/dephosphorylation cycle using the quasi-steady state approximation of enzymatic kinetics. Our aim is to analyze the role of fluctuations and the molecules distribution properties in the transition to a bistable regime. When detailed balance conditions are satisfied it is possible to compute equilibrium distributions in a closed and explicit form. When detailed balance is not satisfied, the stationary non-equilibrium state is strongly influenced by the chemical fluxes. In the last case, we show how the external field derived from the generation and recombination transition rates, can be decomposed by the Helmholtz theorem, into a conservative and a rotational (irreversible) part. Moreover, this decomposition allows to compute the stationary distribution via a perturbative approach. For a finite number of molecules there exists diffusion dynamics in a macroscopic region of the state space where a relevant transition rate between the two critical points is observed. Further, the stationary distribution function can be approximated by the solution of a Fokker-Planck equation. We illustrate the theoretical results using several numerical simulations. PMID- 22779622 TI - On the origin of the unusual behavior in the stretching of single-stranded DNA. AB - Force-extension curves (FECs), which quantify the response of a variety of biomolecules subject to mechanical force (f), are often quantitatively fit using worm-like chain (WLC) or freely jointed chain (FJC) models. These models predict that the chain extension, x, normalized by the contour length increases linearly at small f and at high forces scale as x ~ (1 - f(-alpha)), where alpha = 0.5 for WLC and unity for FJC. In contrast, experiments on single-stranded DNA (ssDNA) show that over a range of f and ionic concentration, x scales as x ~ ln f, which cannot be explained using WLC or FJC models. Using theory and simulations we show that this unusual behavior in FEC in ssDNA is due to sequence-independent polyelectrolyte effects. We show that the x ~ ln f arises because in the absence of force the tangent correlation function, quantifying chain persistence, decays algebraically on length scales on the order of the Debye length. Our theory, which is most appropriate for monovalent salts, quantitatively fits the experimental data and further predicts that such a regime is not discernible in double-stranded DNA. PMID- 22779624 TI - Note: Inverted time-ordering in two-dimensional-Raman-terahertz spectroscopy of water. PMID- 22779623 TI - Low energy electron stimulated desorption from DNA films dosed with oxygen. AB - Desorption of anions stimulated by 1-18 eV electron impact on self-assembled monolayer (SAM) films of single DNA strands is measured as a function of film temperature (50-250 K). The SAMs, composed of 10 nucleotides, are dosed with O(2). The OH(-) desorption yields increase markedly with exposure to O(2) at 50 K and are further enhanced upon heating. In contrast, the desorption yields of O( ), attributable to dissociative electron attachment to trapped O(2) molecules decrease with heating. Irradiation of the DNA films prior to the deposition of O(2) shows that this surprising increase in OH(-) desorption, at elevated temperatures, arises from the reaction of O(2) with damaged DNA sites. These results thus appear to be a manifestation of the so-called "oxygen fixation" effect, well known in radiobiology. PMID- 22779625 TI - Comment on "Dynamical (e, 2e) studies using tetrahydrofuran as a DNA analog" [J. Chem. Phys. 133, 124302 (2010)]. PMID- 22779628 TI - Announcement: new section titles in the Journal of Chemical Physics. PMID- 22779629 TI - Communication: thermodynamic signatures of cluster formation in fluids with competing interactions. AB - Convergent theoretical evidence, based on self-consistent integral equations for the pair structure and on Monte Carlo simulations, is presented for the existence of small simultaneous jump discontinuities of several thermodynamic and structural properties of systems of colloidal particles with competing short range attractive and long-range repulsive interactions, under physical conditions close to the onset of particle clustering. The discontinuities thus provide a signature of the transition from a homogeneous fluid phase to a locally inhomogeneous cluster phase. PMID- 22779630 TI - Communication: phase space approach to laser-driven electronic wavepacket propagation. AB - We propose a phase space method to propagate a quantum wavepacket driven by a strong external field. The method employs the periodic von Neumann basis with biorthogonal exchange recently introduced for the calculation of the energy eigenstates of time-independent quantum systems [A. Shimshovitz and D. J. Tannor, Phys. Rev. Lett. (in press) [e-print arXiv:1201.2299v1]]. While the individual elements in this basis set are time-independent, a small subset is chosen in a time-dependent manner to adapt to the evolution of the wavepacket in phase space. We demonstrate the accuracy and efficiency of the present propagation method by calculating the electronic wavepacket in a one-dimensional soft-core atom interacting with a superposition of an intense, few-cycle, near-infrared laser pulse and an attosecond extreme-ultraviolet laser pulse. PMID- 22779631 TI - Equivalence of the Wei potential model and Tietz potential model for diatomic molecules. AB - By employing the dissociation energy and the equilibrium bond length for a diatomic molecule as explicit parameters, we generate improved expressions for the well-known Rosen-Morse, Manning-Rosen, Tietz, and Frost-Musulin potential energy functions. It is found that the well-known Tietz potential function that is conventionally defined in terms of five parameters [T. Tietz, J. Chem. Phys. 38, 3036 (1963)] actually only has four independent parameters. It is shown exactly that the Wei [Phys. Rev. A 42, 2524 (1990)] and the well-known Tietz potential functions are the same solvable empirical function. When the parameter h in the Tietz potential function has the values 0, +1, and -1, the Tietz potential becomes the standard Morse, Rosen-Morse, and Manning-Rosen potentials, respectively. PMID- 22779632 TI - On the accuracy of frozen density embedding calculations with hybrid and orbital dependent functionals for non-bonded interaction energies. AB - We analyze the accuracy of the frozen density embedding (FDE) method, with hybrid and orbital-dependent exchange-correlation functionals, for the calculation of the total interaction energies of weakly interacting systems. Our investigation is motivated by the fact that these approaches require, in addition to the non additive kinetic energy approximation, also approximate non-additive exact exchange energies. Despite this further approximation, we find that the hybrid/orbital-dependent FDE approaches can reproduce the total energies with the same accuracy (about 1 mHa) as the one of conventional semi-local functionals. In many cases, thanks to error cancellation effects, hybrid/orbital-dependent approaches yield even the smallest error. A detailed energy-decomposition investigation is presented. Finally, the Becke-exchange functional is found to reproduce accurately the non-additive exact-exchange energies also for non equilibrium geometries. These performances are rationalized in terms of a reduced gradient decomposition of the non-additive exchange energy. PMID- 22779633 TI - Static and dynamic coupled perturbed Hartree-Fock vibrational (hyper)polarizabilities of polyacetylene calculated by the finite field nuclear relaxation method. AB - The vibrational contribution to static and dynamic (hyper)polarizability tensors of polyacetylene are theoretically investigated. Calculations were carried out by the finite field nuclear relaxation (FF-NR) method for periodic systems, newly implemented in the CRYSTAL code, using the coupled perturbed Hartree-Fock scheme for the required electronic properties. The effect of the basis set is also explored, being particularly important for the non-periodic direction perpendicular to the polymer plane. Components requiring a finite (static) field in the longitudinal direction for evaluation by the FF-NR method were not evaluated. The extension to that case is currently being pursued. Whereas the effect on polarizabilities is relatively small, in most cases the vibrational hyperpolarizability tensor component is comparable to, or larger than the corresponding static electronic contribution. PMID- 22779634 TI - Assessment of the PW86+PBE+XDM density functional on van der Waals complexes at non-equilibrium geometries. AB - The deficiency of conventional density-functional theory (DFT) in properly describing van der Waals (vdW) (especially dispersion-bound) complexes has been extensively addressed in the past decade. There are now several new methods published in the literature that are capable of accurately capturing weak dispersion interactions in complexes at equilibrium geometries. However, the performance of these new methods at non-equilibrium geometries remains to be assessed. We have previously published [F. O. Kannemann and A. D. Becke, J. Chem. Theory Comput. 6, 1081 (2010); A. D. Becke, A. A. Arabi, and F. O. Kannemann, Can. J. Chem. 88, 1057 (2010)] that the functional PW86+PBE+XDM for exchange + correlation + dispersion, respectively, is a highly accurate functional for general thermochemistry and vdW complexes at equilibrium geometries. Here, we show that this nonempirical, except for two parameters in the dispersion damping part, functional also performs well for vdW complexes at compressed and stretched intermonomer separations. The mean absolute relative error (MARE) is 9.4% overall for vdW complexes in the "S22*5" database incorporating compressed and stretched geometries [J. Rezac, K. E. Riley, and P. Hobza, J. Chem. Theory Comput. 7, 2427 (2011)]. Our largest MARE on the S22*5 database is 13.3% on the compressed geometry set. PMID- 22779635 TI - Database of atomistic reaction mechanisms with application to kinetic Monte Carlo. AB - Kinetic Monte Carlo is a method used to model the state-to-state kinetics of atomic systems when all reaction mechanisms and rates are known a priori. Adaptive versions of this algorithm use saddle searches from each visited state so that unexpected and complex reaction mechanisms can also be included. Here, we describe how calculated reaction mechanisms can be stored concisely in a kinetic database and subsequently reused to reduce the computational cost of such simulations. As all accessible reaction mechanisms available in a system are contained in the database, the cost of the adaptive algorithm is reduced towards that of standard kinetic Monte Carlo. PMID- 22779636 TI - On calculation of thermal conductivity from Einstein relation in equilibrium molecular dynamics. AB - In equilibrium molecular dynamics, Einstein relation can be used to calculate the thermal conductivity. This method is equivalent to Green-Kubo relation and it does not require a derivation of an analytical form for the heat current. However, it is not as commonly used as Green-Kubo relationship. Its wide use is hindered by the lack of a proper definition for integrated heat current (energy moment) under periodic boundary conditions. In this paper, we developed an appropriate definition for integrated heat current to calculate thermal conductivity of solids under periodic conditions. We applied this method to solid argon and silicon based systems; compared and contrasted with the Green-Kubo approach. PMID- 22779637 TI - Breakdown of the pseudopotential approximation for magnetizabilities and electric multipole moments. II. The importance of gauge invariance for large-core semi local pseudopotentials. AB - In a previous paper we pointed out that core contributions to the static magnetizability are non-negligible, and can therefore lead to erroneous results within the pseudopotential approximation [P. Schwerdtfeger, B. Assadollahzadeh, U. Rohrmann, R. Schafer, and J. R. Cheeseman, J. Chem. Phys. 134, 204102 (2011)]. In a recent paper van Wullen showed that additional terms arising from the gauge invariant condition for the semi-local part of a pseudopotential operator can lead to non-negligible contributions to the magnetizability tensor, which are sensitive to the gauge origin and basis set chosen [C. van Wullen, J. Chem. Phys. 136, 114110 (2012)]. These terms were neglected in previous calculations as they were assumed to be small. In this paper we analyze the importance of the gauge dependent semi-local pseudopotential correction term in detail for AuF and clusters of Sn showing that it leads indeed to very large corrections to the paramagnetic term for large-core pseudopotentials. Without this correction the results become very sensitive to the basis set applied. This now resolves some of the unusual large paramagnetic contributions reported before for both AuF and Sn(2). PMID- 22779638 TI - Orbitally invariant internally contracted multireference unitary coupled cluster theory and its perturbative approximation: theory and test calculations of second order approximation. AB - A unitary wave operator, exp (G), G(+) = -G, is considered to transform a multiconfigurational reference wave function Phi to the potentially exact, within basis set limit, wave function Psi = exp (G)Phi. To obtain a useful approximation, the Hausdorff expansion of the similarity transformed effective Hamiltonian, exp (-G)Hexp (G), is truncated at second order and the excitation manifold is limited; an additional separate perturbation approximation can also be made. In the perturbation approximation, which we refer to as multireference unitary second-order perturbation theory (MRUPT2), the Hamiltonian operator in the highest order commutator is approximated by a Moller-Plesset-type one-body zero-order Hamiltonian. If a complete active space self-consistent field wave function is used as reference, then the energy is invariant under orbital rotations within the inactive, active, and virtual orbital subspaces for both the second-order unitary coupled cluster method and its perturbative approximation. Furthermore, the redundancies of the excitation operators are addressed in a novel way, which is potentially more efficient compared to the usual full diagonalization of the metric of the excited configurations. Despite the loss of rigorous size-extensivity possibly due to the use of a variational approach rather than a projective one in the solution of the amplitudes, test calculations show that the size-extensivity errors are very small. Compared to other internally contracted multireference perturbation theories, MRUPT2 only needs reduced density matrices up to three-body even with a non-complete active space reference wave function when two-body excitations within the active orbital subspace are involved in the wave operator, exp (G). Both the coupled cluster and perturbation theory variants are amenable to large, incomplete model spaces. Applications to some widely studied model systems that can be problematic because of geometry dependent quasidegeneracy, H4, P4, and BeH(2), are performed in order to test the new methods on problems where full configuration interaction results are available. PMID- 22779639 TI - Ring polymer dynamics in curved spaces. AB - We formulate an extension of the ring polymer dynamics approach to curved spaces using stereographic projection coordinates. We test the theory by simulating the particle in a ring, T(1), mapped by a stereographic projection using three potentials. Two of these are quadratic, and one is a nonconfining sinusoidal model. We propose a new class of algorithms for the integration of the ring polymer Hamilton equations in curved spaces. These are designed to improve the energy conservation of symplectic integrators based on the split operator approach. For manifolds, the position-position autocorrelation function can be formulated in numerous ways. We find that the position-position autocorrelation function computed from configurations in the Euclidean space R(2) that contains T(1) as a submanifold has the best statistical properties. The agreement with exact results obtained with vector space methods is excellent for all three potentials, for all values of time in the interval simulated, and for a relatively broad range of temperatures. PMID- 22779640 TI - Simultaneous measurement of magnitude and phase in interferometric sum-frequency vibrational spectroscopy. AB - We present a visible-infrared sum-frequency spectroscopic technique that is capable of simultaneously determining the magnitude and phase of the sample response from a single set of experimental conditions. This is especially valuable in cases where the phase stability is high, as in collinear beam geometries, as it enables multiple experiments to be performed without re measuring the local oscillator phase or the reference phase. After illustrating the phase stability achievable with such a geometry, we provide a technique for quantitatively determining the magnitude and phase from a single set of two dimensional spectral-temporal interference fringes. A complete demonstration is provided for the C-H stretching frequency region at the surface of an octadecyltricholosilane film. PMID- 22779641 TI - Near-field focused photoemission from polystyrene microspheres studied with photoemission electron microscopy. AB - We use photoemission electron microscopy (PEEM) to image 3 MUm diameter polystyrene spheres supported on a metal thin film illuminated by 400 nm (~3.1 eV) and 800 nm (~1.5 eV) femtosecond (fs) laser pulses. Intense photoemission is generated by microspheres even though polystyrene is an insulator and its ionization threshold is well above the photon energies employed. We observe intense photoemission from the far side (the side opposite the incident light) of the illuminated microsphere that is attributed to light focusing within the microsphere. For the case of p-polarized, 800 nm fs laser pulses, we observe photoemission exclusively from the far side of the microsphere and additionally resolve sub-50 nm hot spots in the supporting Pt/Pd thin film that are located only within the focal region of the microsphere. We compare the PEEM images with finite difference time domain (FDTD) electrodynamic simulations to model our experimental results. The FDTD simulations predict light focusing in the microsphere and subsequent interaction with the supporting metal surface that is consistent with the experimental observations. PMID- 22779642 TI - Structural properties and energetics of diffuse 87Rb clusters in three-dimension. AB - A correlated two-body basis function is used to describe the three-dimensional bosonic clusters interacting via two-body van der Waals potential. We calculate the ground state and the zero orbital angular momentum excited states for Rb(N) clusters with up to N = 40. We solve the many-particle Schrodinger equation by potential harmonics expansion method, which keeps all possible two-body correlations in the calculation and determines the lowest effective many-body potential. We study energetics and structural properties for such diffuse clusters both at dimer and tuned scattering length. The motivation of the present study is to investigate the possibility of formation of N-body clusters interacting through the van der Waals interaction. We also compare the system with the well studied He, Ne, and Ar clusters. We also calculate correlation properties and observe the generalised Tjon line for large cluster. We test the validity of the shape-independent potential in the calculation of the ground state energy of such diffuse cluster. These are the first such calculations reported for Rb clusters. PMID- 22779643 TI - Infrared spectroscopy of HOCl embedded in superfluid helium nanodroplets: probing the dynamical response of the solvent. AB - The rotationally resolved depletion spectrum of hypochlorous acid embedded in helium nanodroplets in the 2.8 MUm region is reported. The narrow a-type lines are asymmetrically skewed in the direction of the band origin, and an analysis of their line shapes based on the chirped damped oscillator function introduced by van Staveren and Apkarian [J. Chem. Phys. 133, 054506 (2010).] yields a response time of the helium solvent of 1 ns. The b-type lines are much broader due to the greater number of droplet states available for relaxation of the excited rotational states. PMID- 22779644 TI - The photodissociation dynamics of the ethyl radical, C2H5, investigated by velocity map imaging. AB - The photodissociation dynamics of the ethyl radical C(2)H(5) has been investigated by velocity map imaging. Ethyl was produced by flash pyrolysis from n-propyl nitrite and excited to the A (2)A(') (3s) Rydberg state around 250 nm. The energetically most favorable reaction channel in this wavelength region is dissociation to C(2)H(4) (ethene) + H. The H-atom dissociation products were ionized in a [1+1(')] process via the 1s-2p transition. The observed translational energy distribution is bimodal: A contribution of slow H-atoms with an isotropic angular distribution peaks at low translational energies. An expectation value for the fraction of excess energy released into translation of = 0.19 is derived from the data, typical for statistical dissociation reactions. In addition, a fast H-atom channel is observed, peaking around 1.8 eV. The latter shows an anisotropic distribution with beta = 0.45. It originates from a direct dissociation process within less than a rotational period. Time-delay scans with varying extraction voltages indicate the presence of two rates for the formation of H-atoms. One rate with a sub-nanosecond time constant is associated with H-atoms with large translational energy; a second one with a time constant on the order of 100 ns is associated with H-atoms formed with low translational energy. The data confirm and extend those from previous experiments and remove some inconsistencies. Possible mechanisms for the dissociation are discussed in light of the new results as well as previous ones. PMID- 22779645 TI - Exploring the importance of quantum effects in nucleation: the archetypical Ne(n) case. AB - The effect of quantum mechanics (QM) on the details of the nucleation process is explored employing Ne clusters as test cases due to their semi-quantal nature. In particular, we investigate the impact of quantum mechanics on both condensation and dissociation rates in the framework of the microcanonical ensemble. Using both classical trajectories and two semi-quantal approaches (zero point averaged dynamics, ZPAD, and Gaussian-based time dependent Hartree, G-TDH) to model cluster and collision dynamics, we simulate the dissociation and monomer capture for Ne(8) as a function of the cluster internal energy, impact parameter and collision speed. The results for the capture probability P(s)(b) as a function of the impact parameter suggest that classical trajectories always underestimate capture probabilities with respect to ZPAD, albeit at most by 15%-20% in the cases we studied. They also do so in some important situations when using G-TDH. More interestingly, dissociation rates k(diss) are grossly overestimated by classical mechanics, at least by one order of magnitude. We interpret both behaviours as mainly due to the reduced amount of kinetic energy available to a quantum cluster for a chosen total internal energy. We also find that the decrease in monomer dissociation energy due to zero point energy effects plays a key role in defining dissociation rates. In fact, semi-quantal and classical results for k(diss) seem to follow a common "corresponding states" behaviour when the proper definition of internal and dissociation energies are used in a transition state model estimation of the evaporation rate constants. PMID- 22779646 TI - Spectra of water dimer from a new ab initio potential with flexible monomers. AB - We report the definition and testing of a new ab initio 12-dimensional potential for the water dimer with flexible monomers. Using our recent accurate CCpol-8s rigid water pair potential [W. Cencek, K. Szalewicz, C. Leforestier, R. van Harrevelt, and A. van der Avoird, Phys. Chem. Chem. Phys. 10, 4716 (2008)] as a reference for the undistorted monomers' geometries, a distortion correction has been added, which was taken from a former flexible-monomer ab initio potential. This correction allows us to retrieve the correct binding energy D(e)=21.0 kJ mol(-1), and leads to an equilibrium geometry in close agreement with the one obtained from benchmark calculations. The kinetic energy operator describing the flexible-monomer water dimer has been expressed in terms of Radau coordinates for each monomer and a recent general cluster polyspherical formulation describing their relative motions. Within this formulation, an adiabatic scheme has been invoked in order to decouple fast (intramolecular) modes and slow (intermolecular) ones. Different levels of approximation were tested, which differ in the way in which the residual potential coupling between the intramolecular modes located on different monomers and the dependence of the monomer rotational constants on the dimer geometry are handled. Accurate calculations of the vibration-rotation-tunneling levels of (H(2)O)(2) and (D(2)O)(2) were performed, which show the best agreement with experiments achieved so far for any water potential. Intramolecular excitations of the two monomers were calculated within two limiting cases, to account for the lack of non-adiabatic coupling between intramolecular modes due to the intermolecular motion. In the first model, the excitation was assumed to stay either on the donor or the acceptor molecule, and to hop between the two moieties upon donor acceptor interchange. In the second model, the excitation remains on the same molecule whatever is the dimer geometry. Marginal frequency differences, less than 2 cm(-1), were obtained for all modes, and the resulting infrared shifts are in good agreement with experiments. PMID- 22779647 TI - Vibrational calculation for the HOCO radical and the cis-HOCO anion. AB - We present numerically exact vibrational transitions for trans-HOCO, cis-HOCO, and cis-HOCO(-) for the quartic force fields of Fortenberry et al. [J. Chem. Phys. 135, 134301 (2011); ibid. 135, 214303 (2011)], obtained by means of a computational strategy based on the discrete variable representation. Several adiabatic projection schemes have been employed to characterize the vibrational levels and to study the relevance of the intermode coupling (vibrational mixing). Our results help to clear up a large discrepancy between previously reported vibrational perturbation theory and vibrational configuration interaction predictions for the torsional frequency. PMID- 22779648 TI - Frequency-stabilized cavity ring-down spectroscopy measurements of line mixing and collision-induced absorption in the O2 A-band. AB - Frequency-stabilized cavity ring-down spectroscopy measurements were performed in the P-branch of the O(2) A-band [b(1)Sigma(g) (+) <- X (3)Sigma(g) (-)(0,0)] near atmospheric pressure. Line mixing parameters and collision-induced absorption were quantified and reported. These measurements show qualitative differences with those taken at relatively high pressure (2 MPa-20 MPa). We also assess the implications of these measurements on atmospheric retrievals. PMID- 22779649 TI - Sc2@C70 rather than Sc2C2@C68: density functional theory characterization of metallofullerene Sc2C70. AB - Detailed study on Sc(2)C(70) series has been performed based on fully screening for C(70) tetra- and hexa- anions. With a combined methodology of quantum chemistry and statistical mechanics, our calculation results reveal that the Sc(2)C(70), which was proposed as the first metal-carbide endohedral metallofullerene with a non-isolated pentagon rule (non-IPR) cage (Sc(2)C(2)@C(68):6073_C(2v)), is in fact a C(70) non-IPR metallofullerene structure (Sc(2)@C(70):7854_C(2v)) with three pair of pentagon adjacency thanks to its significant thermodynamic and kinetic stability. According to the natural bond analysis and orbital interaction diagram, each scandium atom should only transfer two 4s electrons to the carbon cages and the valence state of Sc(2)@C(70) is (Sc(2+))(2)@C(70) (4-). In addition, the simulation of UV-Vis-NIR spectrum for Sc(2)@C(70):7854_C(2v) shows good accordance to the experimental spectrum. PMID- 22779650 TI - Geometric and electronic structures of (BeO)(N) (N = 2-12, 16, 20, and 24): rings, double rings, and cages. AB - The structure of (BeO)(N) clusters (N = 2-12, 16, 20, and 24) are investigated using the method combining the genetic algorithm with density function theory. Benchmark calculation indicates that THSSh functional is reliable to predict the structures of (BeO)(N) cluster. The global minimum structures of (BeO)(N) clusters are rings up to N = 5, double rings at N = 6 and 7 and cages at N >= 8. Besides, almost all of the structures of (BeO)(N) cluster are aromatic according to the NICS criterion. Adaptive natural density partitioning analysis reveals that C(6), (BN)(3), and (BeO)(3) rings (C(24) and (BeO)(12) fullerenes) are similar in bonding patterns. The building-up principle of (BeO)(N) is different from that of covalent (BN) and ionic (LiF and MgO) clusters. PMID- 22779651 TI - O2(a1Deltag) + Mg, Fe, and Ca: experimental kinetics and formulation of a weak collision, multiwell master equation with spin-hopping. AB - The first excited electronic state of molecular oxygen, O(2)(a(1)Delta(g)), is formed in the upper atmosphere by the photolysis of O(3). Its lifetime is over 70 min above 75 km, so that during the day its concentration is about 30 times greater than that of O(3). In order to explore its potential reactivity with atmospheric constituents produced by meteoric ablation, the reactions of Mg, Fe, and Ca with O(2)(a) were studied in a fast flow tube, where the metal atoms were produced either by thermal evaporation (Ca and Mg) or by pulsed laser ablation of a metal target (Fe), and detected by laser induced fluorescence spectroscopy. O(2)(a) was produced by bubbling a flow of Cl(2) through chilled alkaline H(2)O(2), and its absolute concentration determined from its optical emission at 1270 nm (O(2)(a(1)Delta(g) - X(3)Sigma(g) (-)). The following results were obtained at 296 K: k(Mg + O(2)(a) + N(2) -> MgO(2) + N(2)) = (1.8 +/- 0.2) * 10( 30) cm(6) molecule(-2) s(-1); k(Fe + O(2)(a) -> FeO + O) = (1.1 +/- 0.1) * 10( 13) cm(3) molecule(-1) s(-1); k(Ca + O(2)(a) + N(2) -> CaO(2) + N(2)) = (2.9 +/- 0.2) * 10(-28) cm(6) molecule(-2) s(-1); and k(Ca + O(2)(a) -> CaO + O) = (2.7 +/ 1.0) * 10(-12) cm(3) molecule(-1) s(-1). The total uncertainty in these rate coefficients, which mostly arises from the systematic uncertainty in the O(2)(a) concentration, is estimated to be +/-40%. Mg + O(2)(a) occurs exclusively by association on the singlet surface, producing MgO(2)((1)A(1)), with a pressure dependent rate coefficient. Fe + O(2)(a), on the other hand, shows pressure independent kinetics. FeO + O is produced with a probability of only ~0.1%. There is no evidence for an association complex, suggesting that this reaction proceeds mostly by near-resonant electronic energy transfer to Fe(a(5)F) + O(2)(X). The reaction of Ca + O(2)(a) occurs in an intermediate regime with two competing pressure dependent channels: (1) a recombination to produce CaO(2)((1)A(1)), and (2) a singlet/triplet non-adiabatic hopping channel leading to CaO + O((3)P). In order to interpret the Ca + O(2)(a) results, we utilized density functional theory along with multireference and explicitly correlated CCSD(T)-F12 electronic structure calculations to examine the lowest lying singlet and triplet surfaces. In addition to mapping stationary points, we used a genetic algorithm to locate minimum energy crossing points between the two surfaces. Simulations of the Ca + O(2)(a) kinetics were then carried out using a combination of both standard and non-adiabatic Rice-Ramsperger-Kassel-Marcus (RRKM) theory implemented within a weak collision, multiwell master equation model. In terms of atmospheric significance, only in the case of Ca does reaction with O(2)(a) compete with O(3) during the daytime between 85 and 110 km. PMID- 22779652 TI - A comparison of two-component and four-component approaches for calculations of spin-spin coupling constants and NMR shielding constants of transition metal cyanides. AB - Relativistic density functional theory (DFT) calculations of nuclear spin-spin coupling constants and shielding constants have been performed for selected transition metal (11th and 12th group of periodic table) and thallium cyanides. The calculations have been carried out using zeroth-order regular approximation (ZORA) Hamiltonian and four-component Dirac-Kohn-Sham (DKS) theory with different nonrelativistic exchange-correlation functionals. Two recent approaches for representing the magnetic balance (MB) between the large and small components of four-component spinors, namely, mDKS-RMB and sMB, have been employed for shielding tensor calculations and their results have been compared. Relativistic effects have also been analysed in terms of scalar and spin-orbit contributions at the two-component level of theory, including discussion of heavy-atom-on-light atom effects for (1)J(CN), sigma(C), and sigma(N). The results for molecules containing metals from 4th row of periodic table show that relativistic effects for them are small (especially for spin-spin coupling constants). The biggest effects are observed for the 6th row where nonrelativistic theory reproduces only about 50%-70% of the two-component ZORA results for (1)J(MeC) and about 75% for heavy metal shielding constants. It is important to employ a full Dirac picture for calculations of heavy metal shielding constants, since ZORA reproduces only 75%-90% of the DKS results. Smaller discrepancies between ZORA-DFT and DKS are observed for nuclear spin-spin coupling constants. No significant differences are observed between the results obtained using mDKS-RMB and sMB approaches for magnetic balance in four-component calculations of the shielding constants. PMID- 22779653 TI - Ab initio studies of the interaction potential for the Xe-NO(X2Pi) van der Waals complex: bound states and fully quantum and quasi-classical scattering. AB - Adiabatic potential energy surfaces for the ground electronic state of the Xe???NO(X(2)Pi) van der Waals complex have been calculated using the spin restricted coupled cluster method with single, double, and non-iterative triple excitations (RCCSD(T)). The scalar relativistic effects present in the Xe atom were included by an effective core potential and we extended the basis with bond functions to improve the description of the dispersion interaction. It has been found that the global minimum on the A(') adiabatic surface occurs at a T-shaped geometry with gamma(e) = 94 degrees and R(e) = 7.46 a(0), and with well depth of D(e) = 148.68 cm(-1). There is also an additional local minimum for the collinear geometry Xe-NO with a well depth of 104.5 cm(-1). The adiabat of A('') symmetry exhibits a single minimum at a distance R(e) = 7.68 a(0) and has a skewed geometry with gamma(e) = 64 degrees and a well depth of 148.23 cm(-1). Several C(nl) van der Waals dispersion coefficients are also estimated, of which C(6, 0) and C(6, 2) are in a reasonable agreement with previous theoretical results obtained by Nielson et al. [J. Chem. Phys. 64, 2055 (1976)]. The new potential energy surfaces were used to calculate bound states of the complex for total angular momentum quantum numbers up to J = 7/2. The ground state energy of Xe???NO(X(2)Pi) is D(0) = 117 cm(-1), which matches the experimental value very accurately (within 3.3%). Scattering calculations of integral and differential cross sections have also been performed using fully quantum close coupling calculations and quasi-classical trajectory method at a collision energy of 63 meV. These calculations reveal the important role played by L-type rainbows in the scattering dynamics of the heavier Rg-NO(X) systems. PMID- 22779654 TI - Electronically excited-state properties and predissociation mechanisms of phosphorus monofluoride: a theoretical study including spin-orbit coupling. AB - The 51 Omega states generated from the 22 Lambda - S states of phosphors monofluoride have been investigated using the valence internally contracted multireference configuration interaction method with the Davidson correction and the entirely uncontracted aug-cc-pV5Z basis set. The spin-orbit coupling is computed using the state interaction approach with the Breit-Pauli Hamiltonian. Based on the calculated potential energy curves, the spectroscopic constants of the bound and quasibound Lambda - S and Omega states are obtained, and very good agreement with experiment is achieved. Several quasibound states caused by avoided crossings are found. Various curve crossings and avoided crossings are revealed, and with the help of our computed spin-orbit coupling matrix elements, the predissociation mechanisms of the a(1)Delta, b(1)Sigma(+), e(3)Pi, g(1)Pi, and (3)(3)Pi states are analyzed. The intricate couplings among different electronic states are investigated. We propose that the avoided crossing between the A(3)Pi(0 +) and b(1)Sigma(0+) (+) states may be responsible for the fact that the A(3)Pi nu' >= 12 vibrational levels can not be observed in experiment. The transition properties of the A(3)Pi - X(3)Sigma(-) transition are studied, and our computed Franck-Condon factors and radiative lifetimes match the experimental results very well. PMID- 22779655 TI - The vibrational structure of the oxygen K-shell spectra in acenaphthenequinones: an ab initio study. AB - The vibrational structure of the K-shell O1s -> pi* of acenaphthenequinone C(12)H(6)O(2) and its halogenated compound C(12)H(2)Br(2)Cl(2)O(2) has been simulated using an entirely ab initio approach. For both molecules, analysis of the calculated Franck-Condon factors confirm without ambiguity that, contrary to initial claims, the C-H stretching modes are not modified in the core states and are not excited. For C(12)H(6)O(2), the vibrational fine structure appears to be mainly due to three modes, involving C=O* asymmetric stretch and in-plane ring deformation modes, due to the symmetry breaking of the core state. For C(12)H(2)Br(2)Cl(2)O(2), the vibrational excitation arises essentially from the C=O* asymmetric stretch, with numerous secondary peaks arising from hot and combination bands. For both molecules, these bands are probably responsible for the asymmetry deduced in the experimental fits using a unique Morse potential and initially assigned to anharmonic effects. PMID- 22779656 TI - Ab initio chemical kinetics for the ClOO + NO reaction: effects of temperature and pressure on product branching formation. AB - The kinetics and mechanism for the reaction of ClOO with NO have been investigated by ab initio molecular orbital theory calculations based on the CCSD(T)/6-311+G(3df)//PW91PW91/6-311+G(3df) method, employed to evaluate the energetics for the construction of potential energy surfaces and prediction of reaction rate constants. The results show that the reaction can produce two key low energy products ClNO + (3)O(2) via the direct triplet abstraction path and ClO + NO(2) via the association and decomposition mechanism through long-lived singlet pc-ClOONO and ClONO(2) intermediates. The yield of ClNO + O(2) ((1)?) from any of the singlet intermediates was found to be negligible because of their high barriers and tight transition states. As both key reactions initially occur barrierlessly, their rate constants were evaluated with a canonical variational approach in our transition state theory and Rice-Ramspergen-Kassel-Marcus/master equation calculations. The rate constants for ClNO + (3)O(2) and ClO + NO(2) production from ClOO + NO can be given by 2.66 * 10(-16) T(1.91) exp(341/T) (200 700 K) and 1.48 * 10(-24) T(3.99) exp(1711/T) (200-600 K), respectively, independent of pressure below atmospheric pressure. The predicted total rate constant and the yields of ClNO and NO(2) in the temperature range of 200-700 K at 10-760 Torr pressure are in close agreement with available experimental results. PMID- 22779657 TI - The dynamics of the C + PH3 reaction: a theoretical study. AB - The C + PH(3) reaction is one of the simplest gas-phase processes which can produce molecular species containing P-C bonds. It could be of astrophysical importance and a reference for other phosphine reactions with carbon-containing molecular radicals. The dynamical aspects have been studied theoretically by quasi-classical trajectory methods in order to determine its rate as a function of the temperature, the branching ratios, and the molecular mechanisms. We have obtained a T(0.2) dependence of the capture rate. The total rate is affected by the existence of relatively high-lying saddle points for the isomerization of the CPH(3) complex but get a value of 0.82.10(-10) cm(3) s(-1) at 300 K, which is considered quite high for a neutral-neutral reaction and higher than those of similar reactions. Moreover, the total rate presents a weak dependence with the temperature. Our results indicate that several products containing P-C bonds are formed, the main reaction channel being the generation of HPCH + H. PMID- 22779658 TI - Probing the structures of neutral boron clusters using infrared/vacuum ultraviolet two color ionization: B11, B16, and B17. AB - The structures of neutral boron clusters, B(11), B(16), and B(17), have been investigated using vibrational spectroscopy and ab initio calculations. Infrared absorption spectra in the wavelength range of 650 to 1550 cm(-1) are obtained for the three neutral boron clusters from the enhancement of their near-threshold ionization efficiency at a fixed UV wavelength of 157 nm (7.87 eV) after resonant absorption of the tunable infrared photons. All three clusters, B(11), B(16), and B(17), are found to possess planar or quasi-planar structures, similar to their corresponding anionic counterparts (B(n) (-)), whose global minima were found previously to be planar, using photoelectron spectroscopy and theoretical calculations. Only minor structural changes are observed between the neutral and the anionic species for these three boron clusters. PMID- 22779659 TI - Aqueous tert-butanol mixtures: a model for molecular-emulsions. AB - By analogy with micro-emulsion, we introduce the molecular-emulsion picture to describe particular aqueous mixtures. The analogy is set by introducing the equivalent of the Teubner-Strey structure factor, the latter which is traditionally used to describe the structure of micro-emulsions. The main difference resides in the fact that the size of the oil and water domains are not in the micrometer, but in the nanometer scale. This implies that the molecular size and the molecular geometry cannot be neglected anymore. The introduction of this analogy is used to settle the problem of properly describing with computer simulations highly micro-heterogeneous aqueous mixtures. In particular, the issue of whether or not the Kirkwood-Buff integrals represent solely concentration fluctuations is settled by showing the contribution of the micro-heterogeneity to these integrals through the presence of an associated pre-peak in the structure factors. Both the Optimized Potentials for Liquid State (OPLS) and Transferable Potential for Phase Equilibria-United Atoms (TraPPE-UA) force fields for tert butanol turn out to be remarkably good in describing the structure of the corresponding aqueous mixtures, when the above-mentioned analogy with micro emulsion is introduced to correct for the computational artifacts in the Kirkwood Buff integrals. PMID- 22779660 TI - Direct calculation of 1-octanol-water partition coefficients from adaptive biasing force molecular dynamics simulations. AB - The 1-octanol-water partition coefficient log K(ow) of a solute is a key parameter used in the prediction of a wide variety of complex phenomena such as drug availability and bioaccumulation potential of trace contaminants. In this work, adaptive biasing force molecular dynamics simulations are used to determine absolute free energies of hydration, solvation, and 1-octanol-water partition coefficients for n-alkanes from methane to octane. Two approaches are evaluated; the direct transfer of the solute from 1-octanol to water phase, and separate transfers of the solute from the water or 1-octanol phase to vacuum, with both methods yielding statistically indistinguishable results. Calculations performed with the TIP4P and SPC/E water models and the TraPPE united-atom force field for n-alkanes show that the choice of water model has a negligible effect on predicted free energies of transfer and partition coefficients for n-alkanes. A comparison of calculations using wet and dry octanol phases shows that the predictions for log K(ow) using wet octanol are 0.2-0.4 log units lower than for dry octanol, although this is within the statistical uncertainty of the calculation. PMID- 22779661 TI - Tracer diffusion in colloidal suspensions under dilute and crowded conditions with hydrodynamic interactions. AB - We consider tracer diffusion in colloidal suspensions under solid loading conditions, where hydrodynamic interactions play an important role. To this end, we carry out computer simulations based on the hybrid stochastic rotation dynamics-molecular dynamics (SRD-MD) technique. Many details of the simulation method are discussed in detail. In particular, our choices for the SRD-MD parameters and for the different scales are adapted to simulating colloidal suspensions under realistic conditions. Our simulation data are compared with published theoretical, experimental and numerical results and compared to Brownian dynamics simulation data. We demonstrate that our SRD-MD simulations reproduce many features of the hydrodynamics in colloidal fluids under finite loading. In particular, finite-size effects and the diffusive behavior of colloids for a range of volume fractions of the suspension show that hydrodynamic interactions are correctly included within the SRD-MD technique. PMID- 22779662 TI - Colloidal electroconvection in a thin horizontal cell. III. Interfacial and transient patterns on electrodes. AB - Previously we have reported a family of convective patterns formed by charge stabilized aqueous colloidal suspensions under constant (dc) vertical electric fields [Y. Han and D. G. Grier, J. Chem. Phys. 122, 164701 (2005); and ibid. 125, 144707 (2006)]. These patterns form in the bulk when electrokinetic forces act in the opposite direction to gravity. Here, we report on cellular patterns that silica colloidal spheres form on a horizontal electrode when electrokinetic forces act in the same direction as gravity. We suggest that these cellular patterns form as a result of bulk electroconvection mediated by charge injection into the supporting aqueous electrolyte. This charge-injection mechanism also accounts for some aspects of electroconvective pattern formation in our earlier reports. Cellular patterns reorganize themselves into distinct transient patterns after the driving voltage is turned off. These transients cast new light on the complex interplay between the motions of charged colloidal spheres and the ionic relaxation of water undergoing electrolysis. PMID- 22779664 TI - The origin of persistent shear stress in supercooled liquids. AB - The persistence of shear stress fluctuations in viscous liquids is a direct consequence of the non-zero shear stress of the local potential minima which couples stress relaxation to transitions between inherent structures. In simulations of 2D and 3D glass forming mixtures, we calculate the distribution of this inherent shear stress and demonstrate that the variance is independent of temperature and obeys a power law in density. The inherent stress is shown to involve only long wavelength fluctuations, evidence of the central role of the static boundary conditions in determining the residual stress left after the minimization of the potential energy. A temperature T(eta) is defined to characterise the crossover from stress relaxation governed by binary collisions at high temperatures to low temperature relaxation dominated by the relaxation of the inherent stress. T(eta) is found to coincide with the breakdown of the Stokes Einstein scaling of diffusion and viscosity. PMID- 22779663 TI - Matrix-isolation infrared studies of 1:1 molecular complexes containing chloroform (CHCl3) and Lewis bases: seamless transition from blue-shifted to red shifted hydrogen bonds. AB - The infrared spectra of molecular complexes containing chloroform (CHCl(3)) and Lewis bases (N(2), CO, H(2)O, and CH(3)CN) have been observed in an Ar matrix, and vibrational peaks for the 1:1 complexes have been assigned. The C-H stretching band of chloroform in the complexes showed a seamless transition from a blue shift (for N(2) and CO) to a red shift (H(2)O and CH(3)CN), in accord with the proton affinity of the base molecules. Density functional calculations predicted that the C-H..(sigma-type lone pair) isomer is the most stable, which is consistent with the observed vibrational peak shift upon complex formation. The underlying mechanisms of the C-H hydrogen bond were explored using the topological properties of the electronic charge density and natural orbital analyses. PMID- 22779665 TI - Excitation and emission spectra of rubidium in rare-gas thin-films. AB - To understand the optical properties of atoms in solid state matrices, the absorption, excitation, and emission spectra of rubidium doped thin-films of argon, krypton, and xenon were investigated in detail. A two-dimensional spectral analysis extends earlier reports on the excitation and emission properties of rubidium in rare-gas hosts. We found that the doped crystals of krypton and xenon exhibit a simple absorption-emission relation, whereas rubidium in argon showed more complicated spectral structures. Our sample preparation employed in the present work yielded different results for the Ar crystal, but our peak positions were consistent with the prediction based on the linear extrapolation of Xe and Kr data. We also observed a bleaching behavior in rubidium excitation spectra, which suggests a population transfer from one to another spectral feature due to hole-burning. The observed optical response implies that rubidium in rare-gas thin-films is detectable with extremely high sensitivity, possibly down to a single atom level, in low concentration samples. PMID- 22779666 TI - Up to fourth virial coefficients from simple and efficient internal-coordinate sampling: application to neon. AB - A simple and efficient internal-coordinate importance sampling protocol for the Monte Carlo computation of (up to fourth-order) virial coefficients B(n) of atomic systems is proposed. The key feature is a multivariate sampling distribution that mimics the product structure of the dominating pairwise additive parts of the B(n). This scheme is shown to be competitive over routine numerical methods and, as a proof of principle, applied to neon: The second, third, and fourth virial coefficients of neon as well as equation-of-state data are computed from ab initio two- and three-body potentials; four-body contributions are found to be insignificant. Kirkwood-Wigner quantum corrections to first order are found to be crucial to the observed agreement with recent ab initio and experimental reference data sets but are likely inadequate at very low temperatures. PMID- 22779667 TI - Entropy production in non-equilibrium fluctuating hydrodynamics. AB - Fluctuating entropy production is studied for a set of linearly coupled complex fields. The general result is applied to non-equilibrium fluctuating hydrodynamic equations for coarse-grained fields (density, temperature, and velocity), in the framework of model granular fluids. We find that the average entropy production, obtained from the microscopic stochastic description, can be expressed in terms of macroscopic quantities, in analogy with linear non-equilibrium thermodynamics. We consider the specific cases of driven granular fluids with two different kinds of thermostat and the homogeneous cooling regime. In all cases, the average entropy production turns out to be the product of a thermodynamic force and a current: the former depends on the specific energy injection mechanism, the latter takes always the form of a static correlation between fluctuations of density and temperature time-derivative. Both vanish in the elastic limit. The behavior of the entropy production is studied at different length scales and the qualitative differences arising for the different granular models are discussed. PMID- 22779668 TI - Predicting the melting temperature of ice-Ih with only electronic structure information as input. AB - The melting temperature of ice-Ih was calculated with only electronic structure information as input by creating a problem-specific force field. The force field, Water model by AFM for Ice and Liquid (WAIL), was developed with the adaptive force matching (AFM) method by fitting to post-Hartree-Fock quality forces obtained in quantum mechanics/molecular mechanics calculations. WAIL predicts the ice-Ih melting temperature to be 270 K. The model also predicts the densities of ice and water, the temperature of maximum density of water, the heat of vaporizations, and the radial distribution functions for both ice and water in good agreement with experimental measurements. The non-dissociative WAIL model is very similar to a flexible version of the popular TIP4P potential and has comparable computational cost. By customizing to problem-specific configurations with the AFM approach, the resulting model is remarkably more accurate than any variants of TIP4P for simulating ice-Ih and water in the temperature range from 253 K and 293 K under ambient pressure. PMID- 22779669 TI - Explicit water molecular dynamics study of the mobility of halide ions in presence of ionene oligocations. AB - We present explicit water molecular dynamics simulations of solutions of aliphatic 3,3- and 6,6-ionene oligocations neutralized with (i) fluoride, chloride, bromide, or iodide counterions, respectively, or (ii) with a 1:1 mixture of chloride and bromide anions in presence of a low molecular weight salt at 298 K. The SPC/E model was used to describe water molecules. Results of the simulation are presented in form of the pair distribution functions between various atoms on the ionene oligoion and counterions in solution. In addition, we were interested in the dynamics of counterions around model ionenes. We showed that counterions residing in the vicinity of the oligoion exchange rapidly with those in the bulk solution, with the frequency depending on the nature of the counterion and on the charge density of the oligoion. We calculated the average residence times of the various counterion species to the oligoions and proposed the model which divides the counterions into "free" and "bound" and calculated the fraction of "free" counterions. In the second part of the study, we investigated interaction of the sodium chloride and sodium bromide, being simultaneously present in the solution, with differently charged ionenes in water. The selectivity effect was clearly observed: bromide ions tend to replace chloride ions in the immediate vicinity of the ionene oligoions. Simulation results are discussed in light of our recent measurements of thermodynamic and transport properties of aqueous ionene solutions. PMID- 22779670 TI - Identification of unavoided crossings in nonadiabatic photoexcited dynamics involving multiple electronic states in polyatomic conjugated molecules. AB - Radiationless transitions between electronic excited states in polyatomic molecules take place through unavoided crossings of the potential energy surfaces with substantial non-adiabatic coupling between the respective adiabatic states. While the extent in time of these couplings are large enough, these transitions can be reasonably well simulated through quantum transitions using trajectory surface hopping-like methods. In addition, complex molecular systems may have multiple "trivial" unavoided crossings between noninteracting states. In these cases, the non-adiabatic couplings are described as sharp peaks strongly localized in time. Therefore, their modeling is commonly subjected to the identification of regions close to the particular instantaneous nuclear configurations for which the energy surfaces actually cross each other. Here, we present a novel procedure to identify and treat these regions of unavoided crossings between non-interacting states using the so-called Min-Cost algorithm. The method differentiates between unavoided crossings between interacting states (simulated by quantum hops), and trivial unavoided crossings between non interacting states (detected by tracking the states in time with Min-Cost procedure). We discuss its implementation within our recently developed non adiabatic excited state molecular dynamics framework. Fragments of two- and four ring linear polyphenylene ethynylene chromophore units at various separations have been used as a representative molecular system to test the algorithm. Our results enable us to distinguish and analyze the main features of these different types of radiationless transitions the molecular system undertakes during internal conversion. PMID- 22779671 TI - A minimal model for excitons within time-dependent density-functional theory. AB - The accurate description of the optical spectra of insulators and semiconductors remains an important challenge for time-dependent density-functional theory (TDDFT). Evidence has been given in the literature that TDDFT can produce bound as well as continuum excitons for specific systems, but there are still many unresolved basic questions concerning the role of dynamical exchange and correlation (xc). In particular, the roles of the long spatial range and the frequency dependence of the xc kernel f(xc) for excitonic binding are still not very well explored. We present a minimal model for excitons in TDDFT, consisting of two bands from a one-dimensional (1D) Kronig-Penney model and simple approximate xc kernels, providing an easily accessible model system for studying excitonic effects in TDDFT. For the 1D model system, it is found that adiabatic xc kernels can produce at most two bound excitons, confirming that the long spatial range of f(xc) is not a necessary condition. It is shown how the Wannier model, featuring an effective electron-hole interaction, emerges from TDDFT. The collective, many-body nature of excitons is explicitly demonstrated. PMID- 22779672 TI - Acoustic properties of Kel F-800 copolymer up to 85 GPa. AB - Acoustic properties of the fluorinated copolymer Kel F-800 were determined with Brillouin spectroscopy up to pressures of 85 GPa at 300 K. This research addresses outstanding issues in high-pressure polymer behavior, as to date the acoustic properties and equation of state of any polymer have not been determined above 20 GPa. We observed both longitudinal and transverse modes in all pressure domains, allowing us to calculate the C(11) and C(12) moduli, bulk, shear, and Young's moduli, and the density of Kel F-800 as a function of pressure. We found the behavior of the polymer with respect to all parameters to change drastically with pressure. As a result, we find that the data are best understood when split into two pressure regimes. At low pressures (less than ~5 GPa), analysis of the room temperature isotherm with a semi-empirical equation of state yielded a zero pressure bulk modulus K(o) and its derivative K(0) (') of 12.8 +/- 0.8 GPa and 9.6 +/- 0.7, respectively. The same analysis for the higher pressure data yielded values for K(o) and K(0) (') of 34.9 +/- 1.7 GPa and 5.1 +/- 0.1, respectively. We discuss this significant difference in behavior with reference to the concept of effective free volume collapse. PMID- 22779673 TI - Non-monotonic, distance-dependent relaxation of water in reverse micelles: propagation of surface induced frustration along hydrogen bond networks. AB - Layer-wise, distance-dependent orientational relaxation of water confined in reverse micelles (RM) is studied using theoretical and computational tools. We use both a newly constructed "spins on a ring" (SOR) Ising-type model (with Shore Zwanzig rotational dynamics) and atomistic simulations with explicit water. Our study explores the effect of reverse micelle size and role of intermolecular correlations, compromised by the presence of a highly polar surface, on the distance (from the interface) dependence of water relaxation. The "spins on a ring" model can capture some aspects of distance dependence of relaxation, such as acceleration of orientational relaxation at intermediate layers. In atomistic simulations, layer-wise decomposition of hydrogen bond formation pattern clearly reveals that hydrogen bond arrangement of water at a certain distance away from the surface can remain frustrated due to the interaction with the polar surface head groups. This layer-wise analysis also reveals the presence of a non monotonic slow relaxation component which can be attributed to this frustration effect and which is accentuated in small to intermediate size RMs. For large size RMs, the long time component decreases monotonically from the interface to the interior of the RMs with slowest relaxation observed at the interface. PMID- 22779674 TI - Hydrogen adsorbed in a metal organic framework-5: coupled translation-rotation eigenstates from quantum five-dimensional calculations. AB - We report rigorous quantum five-dimensional (5D) calculations of the coupled translation-rotation (T-R) eigenstates of a H(2) molecule adsorbed in metal organic framework-5 (MOF-5), a prototypical nanoporous material, which was treated as rigid. The anisotropic interactions between H(2) and MOF-5 were represented by the analytical 5D intermolecular potential energy surface (PES) used previously in the simulations of the thermodynamics of hydrogen sorption in this system [Belof et al., J. Phys. Chem. C 113, 9316 (2009)]. The global and local minima on this 5D PES correspond to all of the known binding sites of H(2) in MOF-5, three of which, alpha-, beta-, and gamma-sites are located on the inorganic cluster node of the framework, while two of them, the delta- and epsilon-sites, are on the phenylene link. In addition, 2D rotational PESs were calculated ab initio for each of these binding sites, keeping the center of mass of H(2) fixed at the respective equilibrium geometries; purely rotational energy levels of H(2) on these 2D PESs were computed by means of quantum 2D calculations. On the 5D PES, the three adjacent gamma-sites lie just 1.1 meV above the minimum-energy alpha-site, and are separated from it by a very low barrier. These features allow extensive wave function delocalization of even the lowest translationally excited T-R eigenstates over the alpha- and gamma-sites, presenting significant challenges for both the quantum bound-state calculations and the analysis of the results. Detailed comparison is made with the available experimental data. PMID- 22779675 TI - Theory of repulsive charged colloids in slit-pores. AB - Using classical density functional theory (DFT) we analyze the structure of the density profiles and solvation pressures of negatively charged colloids confined in slit pores. The considered model, which was already successfully employed to study a real colloidal (silica) suspension [S. H. L. Klapp et al., Phys. Rev. Lett. 100, 118303 (2008)], involves only the macroions which interact via the effective Derjaguin-Landau-Verwey-Overbeek (DLVO) potential supplemented by a hard core interaction. The solvent enters implicitly via the screening length of the DLVO interaction. The free energy functional describing the colloidal suspension consists of a hard sphere contribution obtained from fundamental measure theory and a long range contribution which is treated using two types of approximations. One of them is the mean field approximation (MFA) and the remaining is based on Rosenfeld's perturbative method for constructing the Helmholtz energy functional. These theoretical calculations are carried out at different bulk densities and wall separations to compare finally to grand canonical Monte Carlo simulations. We also consider the impact of charged walls. Our results show that the perturbative DFT method yields generally qualitatively consistent and, for some systems, also quantitatively reliable results. In MFA, on the other hand, the neglect of charge-induced correlations leads to a breakdown of this approach in a broad range of densities. PMID- 22779676 TI - Origin of synergistic effect over Ni-based bimetallic surfaces: a density functional theory study. AB - Density functional theory calculations have been conducted to explore the physical origin of the synergistic effect over Ni-based surface alloys using methane dissociation as a probe reaction. Some late transition metal atoms (M = Cu, Ru, Rh, Pd, Ag, Pt, and Au) are substituted for surface Ni atoms to examine the variation in electronic structure and adsorption property of Ni(111). Two types of threefold hollow sites, namely, the Ni(2)M and Ni(3) sites, are taken into account. The calculated results indicate that the variation in the CH(x) adsorption energy at the Ni(2)M and Ni(3) sites is dominated by the ensemble and ligand effect, respectively, and the other factors such as surface and adsorbate distortion and electrostatic interaction affect the catalytic properties of the bimetallic surfaces to a smaller extent. Both the Bronsted-Evans-Polanyi relationship and the scaling correlation hold true on the Ni-based bimetallic surfaces. With the combination of these two linear energy relations, the corrected binding energy of atomic C is found to be a good descriptor for representing the catalytic activity of the alloyed surfaces. Considering the compromise between the catalytic activity and catalyst stability, we suggest that the Rh/Ni catalyst is a good candidate for methane dissociation. PMID- 22779677 TI - Simulation of tethered oligomers in nanochannels using multi-particle collision dynamics. AB - The effect of a high Reynold's number, pressure-driven flow of a compressible gas on the conformation of an oligomer tethered to the wall of a square channel is studied under both ideal solvent and poor solvent conditions using a hybrid multiparticle collision dynamics and molecular dynamics algorithm. Unlike previous studies, the flow field contains an elongational component in addition to a shear component as well as fluid slip near the walls and results in a Schmidt number for the polymer beads that is less than unity. In both solvent regimes the oligomer is found to extend in the direction of flow. Under the ideal solvent conditions, torsional twisting of the chain and aperiodic cyclical dynamics are observed for the end of the oligomer. Under poor solvent conditions, a metastable helix forms in the end of the chain despite the lack of any attractive potential between beads in the oligomeric chain. The formation of the helix is postulated to be the result of a solvent induced chain collapse that has been confined to a single dimension by a strong flow field. PMID- 22779678 TI - Coarse graining of star-polymer--colloid nanocomposites. AB - We consider mixtures of self-avoiding multiarm star polymers with hard colloids that are smaller than the star polymer size. By employing computer simulations, and by extending previous theoretical approaches, developed for the opposite limit of small star polymers [A. Jusufi et al., J. Phys.: Condens. Matter 13, 6177 (2001)], we coarse-grain the mixture by deriving an effective cross interaction between the unlike species. The excellent agreement between theory and simulation for all size ratios examined demonstrates that the theoretical approaches developed for the colloidal limit can be successfully modified to maintain their validity also for the present case of the protein limit, in contrast to the situation for mixtures of colloids and linear polymers. We further analyze, on the basis of the derived interactions, the non-additivity parameter of the mixture as a function of size ratio and star functionality and delineate the regions in which we expect mixing as opposed to demixing behavior. Our results are relevant for the study of star-colloid nanocomposites and pave the way for further investigations of the structure and thermodynamics of the same. PMID- 22779679 TI - Dynamic Monte Carlo modeling of exciton dissociation in organic donor-acceptor solar cells. AB - A general dynamic Monte Carlo model for exciton dissociation at a donor-acceptor interface that includes exciton delocalization and hot charge separation is developed to model the experimental behavior observed for the poly(3 hexylthiophene):fullerene system and predict the theoretical performance of future materials systems. The presence of delocalized excitons and the direct formation of separated charge pairs has been recently measured by transient photo induced absorption experiments and has been proposed to facilitate charge separation. The excess energy of the exciton dissociation process has also been observed to have a strong correlation with the charge separation yield for a series of thiophene based polymer:fullerene systems, suggesting that a hot charge separation process is also occurring. Hot charge separation has been previously theorized as a cause for highly efficient charge separation. However, a detailed model for this process has not been implemented and tested. Here, both conceptual models are implemented into a dynamic Monte Carlo simulation and tested using a simple bilayer donor-acceptor system. We find that exciton delocalization can account for a significant reduction in geminate recombination when compared to the traditional, bound polaron pair model. In addition, the hot charge separation process could further reduce the geminate recombination, but only if the hot charge mobility is several orders of magnitude larger than the standard charge mobility. PMID- 22779680 TI - Separation of components in lipid membranes induced by shape transformation. AB - Vesicles composed of a two component membrane with each component characterized by different spontaneous curvature are investigated by minimization of the free energy consisting of Helfrich elastic energy and entropy of mixing. The results show that mixing and demixing of membrane components can be induced by elongating a vesicle or changing its volume, if one of the components forms a complex with macromolecules on the outer monolayer. The influence of elastic coefficients on the separation of components is also examined. PMID- 22779681 TI - Critical role in CXCR4 signaling and internalization of the polypeptide main chain in the amino terminus of SDF-1alpha probed by novel N-methylated synthetically and modularly modified chemokine analogues. AB - The replication of human immunodeficiency virus type 1 (HIV-1) can be profoundly inhibited by the natural ligands of two major HIV-1 coreceptors, CXCR4 and CCR5. Stromal cell-derived factor-1alpha (SDF-1alpha) is a natural ligand of CXCR4. We have recently developed a synthetic biology approach of using synthetically and modularly modified (SMM)-chemokines to dissect various aspects of the structure function relationship of chemokines and their receptors. Here, we used this approach to design novel SMM-SDF-1alpha analogues containing unnatural N methylated residues in the amino terminus to investigate whether the polypeptide main chain amide bonds in the N-terminus of SDF-1alpha play a role in SDF-1alpha signaling via CXCR4 and/or receptor internalization. The results show that SDF 1alpha analogues with a modified N-methylated main chain at position 2, 3, or 5 retain significant CXCR4 binding and yet completely lose signaling activities. Furthermore, a representative N-methylated analogue has been shown to be incapable of causing CXCR4 internalization. These results suggest that the ability of SDF-1alpha to activate CXCR4 signaling and internalization is dependent upon the main chain amide bonds in the N-terminus of SDF-1alpha. This study demonstrates the feasibility and value of applying a synthetic biology approach to chemically engineer natural proteins and peptide ligands as probes of important biological functions that are not addressed by other biological techniques. PMID- 22779682 TI - Strong biofilm production but not adhesion virulence factors can discriminate between invasive and commensal Staphylococcus epidermidis strains. AB - Staphylococcus epidermidis is a leading cause of hospital-acquired infections, mostly associated with the use of medical devices in immunocompromised patients. It originates from the patient's own skin flora, which is subject to severe changes as a result of selective pressure exerted by the hospital environment. This notion led us to compare S. epidermidis isolates from catheter related infections (CRI), non-catheter related bacteremia (NCRB) and catheter hub cultures (commensal isolates). The collection comprised 47 CRI strains from the Bone Marrow Transplant Centre of Tunis, 25 NCRB strains and 25 commensal isolates from patients hospitalized in the same center. Antimicrobial resistance and virulence-associated genes (icaABC, aap, atlE, bhp, fbe, embp, and IS256), polysaccharide intercellular adhesin synthesis, and biofilm formation were investigated. The clonal relationship of strains was investigated by pulsed field gel electrophoresis. Whereas bhp, atlE, fbe, embp, and aap were almost ubiquitously amplified, resistance to oxacillin, kanamycin, tobramycin, gentamicin, cotrimoxazole, and fosfomycin, biofilm production, ica genes, and IS256 were significantly more frequent in invasive (CRI and NCRB strains) than in commensal strains. Moreover, strong biofilm production was significantly more frequent among CRI strains than in NCRB strains. In conclusion, when S. epidermidis is isolated from blood cultures, the detection of strong biofilm production may be significant with regard to judging whether the detected strain is an etiologic agent of CRI. PMID- 22779683 TI - First outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a Norwegian neonatal intensive care unit; associated with contaminated breast milk and resolved by strict cohorting. AB - Neonatal intensive care units (NICUs) are vulnerable to nosocomial outbreaks caused by multiresistant Enterobacteriaceae, but no reports of NICU outbreaks of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae have previously been published from countries with a low level of antimicrobial resistance such as the Scandinavian countries. We describe a clonal outbreak of CTX-M-15 -producing Klebsiella pneumoniae affecting 58 infants in the neonatal intensive care unit at Stavanger University Hospital, Norway, during a period of 4 months, 2008-2009. The clone spread widely and rapidly in the NICU, and extensive interventions were required to terminate the outbreak. In contrast to previous outbreaks, only one infant acquired a systemic infection caused by the outbreak strain, probably due to a favourable epidemic strain lacking the most common virulence factors. A probable index case was identified, due to multiple positive breast milk samples collected from the infant's mother before and after the infant's transfer from another hospital. Breast milk samples from 3/18 (17%) mothers of colonized infants were positive for ESBL-producing K. pneumoniae. Vertical transmission of ESBL-producing bacteria has been shown previously,’but the possibility of transmission of ESBL-producing K. pneumoniae through expressed breast milk is reported here for the first time. The increasing occurrence of ESBL-producing’Enterobacteriaceae should therefore encourage changes in diagnostic routines for bacterial screening of breast milk. PMID- 22779684 TI - Type III apparatus of Pseudomonas aeruginosa as a tool to diagnose pulmonary infection in cystic fibrosis patients. AB - Pseudomonas aeruginosa is associated with increased mortality in cystic fibrosis (CF) patients, and expresses type III secretion system proteins (TTSP), which is a common mechanism used by gram-negative pathogens for delivery of anti-host factors. Our aim was to investigate whether or not these antigens (TTSP) would be recognized by CF sera, by Western blot reaction. We have showed herein that all patients (n = 11) not chronically infected by P. aeruginosa had their first serum positive for TTSP (ExoS, ExoT, PopB, and/or PopD). All chronic patients had a strong positive serology to TTSP, although relatively weak reactions to TTSP were observed for some individuals in the negative control group. Therefore, TTSP that were early produced in P. aeruginosa infected CF patients, induced a detectable antibody response in those patients and were easily detected by Western-blot reaction. PMID- 22779685 TI - Peripheral autonomic nerves of human pineal organ terminate on vessels, their supposed role in the periodic secretion of pineal melatonin. AB - Nonvisual pineal and retinal photoreceptors are synchronizing circadian and circannual periodicity to the environmental light periods in the function of various organs. Melatonin of the pineal organ is secreted at night and represents an important factor of this periodic regulation. Night illumination suppressing melatonin secretion may result in pathological events like breast and colorectal cancer. Experimental works demonstrated the role of autonomic nerves in the pineal melatonin secretion. It was supposed that mammalian pineals have lost their photoreceptor capacity that is present in submammalians, and sympathetic fibers would mediate light information from the retina to regulate melatonin secretion. Retinal afferentation may reach the organ by central nerve fibers via the pineal habenulae as well. In our earlier works we have found that the pineal organ developing from lobular evaginations of the epithalamus differs from peripheral endocrine glands and is composed of a retina-like central nervous tissue that is comprised of cone-like pinealocytes, secondary pineal neurons and glial cells. Their autonomic nerves in submammalians as well as in mammalian animals do not terminate on pineal cells, rather, they run in the meningeal septa among pineal lobules and form vasomotor nerve endings. Concerning the adult human pineal there are no detailed fine structural data about the termination of autonomic fibers, therefore, in the present work we investigated the ultrastructure of the human pineal peripheral autonomic nerve fibers. It was found, that similarly to other parts of the brain, autonomic nerves do not enter the human pineal nervous tissue itself but separated by glial limiting membranes take their course in the meningeal septa of the organ and terminate on vessels by vasomotor endings. We suppose that these autonomic vasomotor nerves serve the regulation of the pineal blood supply according to the circadian and circannual changes of the metabolic activity of the organ and support by this effect the secretion of pineal neurohormones including melatonin. PMID- 22779686 TI - Mutational analysis of PIK3CA, JAK2, BRAF, FOXL2, IDH1, AKT1 and EZH2 oncogenes in sarcomas. AB - Recent studies have revealed several recurrent mutations in oncogenes that could not only be underlying mechanisms of tumorigenesis, but also be potential targets for cancer therapies. Compared to carcinomas, genetic alterations of sarcomas are relatively unknown. To see whether recurrent oncogenes discovered in non sarcomatous malignancies are present in sarcomas as well, we analyzed oncogenes with known mutations in various types of sarcomas. We performed mutational analysis of recurrent mutation sites of PIK3CA (exons 9 and 20), JAK2 (exon 14), BRAF (exon 15), FOXL2 (exon 1), IDH1 (exon 4), AKT1 (exon 3), and EZH2 (exon 16) genes in 108 sarcomas by single- strand conformation polymorphism and DNA sequencing. The sarcomas consisted of malignant fibrous histiocytomas, rhabdomyosarcomas, osteosarcomas, malignant peripheral nerve sheath tumors, leiomyosarcomas, synovial sarcomas, liposarcomas, angiosarcomas, chondrosarcomas, and Ewing sarcomas. Overall, we detected the two PIK3CA mutations and one JAK2 mutation (total: 3/108: 2.8%). Two rhabdomyosarcomas (16.7%) and one angiosarcoma (16.7%) harbored the mutations, whereas other sarcomas harbored none. The PIK3CA mutations were novel missense mutations that had not been detected in other cancers. The JAK2 mutation was an intron mutation. This study demonstrated that the somatic mutations of PIK3CA and JAK2 occurred in a small fraction of the sarcomas and that these mutations may not play a principal role in the development of sarcomas. PMID- 22779687 TI - Proliferative activity and histopathological features in diffuse grade II astrocytomas. AB - Due to the heterogeneous histopathology of diffuse astrocytomas we wanted to investigate the frequency of various histological features in grade II tumours. Herein we present the results of a microscopical examination and revision of 109 consecutively operated grade II tumours. The most frequent subtype was fibrillary astrocytoma (87%), whereas the gemistocytic and protoplasmic subtypes constituted 12% and 1% respectively. Cell density was subjectively classified and ranged from low to high; most cases were judged as low to moderate (approx. 90%). Cellular/nuclear atypia was assessed as mild, moderate and severe, and was in the majority of cases mild to moderate (96%). Mitoses were observed in about 25% of the cases with a median of 0 (range 0-3). Apoptotic figures, microcystic changes, Rosenthal fibres, microcalcification and eosinophilic bodies were identified in approx. 45%, 38%, 7%, 5% and 2% of the cases respectively. In about 60% of the cases so called secondary changes of Scherer were seen. Significant correlations between features related to malignancy, such as mitotic activity, apoptoses and high cell density, were established. Further, Ki-67/MIB-1 proliferation indices corresponded significantly with mitoses, apoptoses, atypia and high cell density. Accordingly, the variegated histopathological appearance of diffuse astrocytomas makes the diagnosis of these tumours challenging. Accordingly, it is essential to know and be aware of this morphological diversity in the daily routine. The use of Ki-67/MIB-1 immunostaining may improve the diagnostic accuracy. PMID- 22779688 TI - The cuprizone model: regional heterogeneity of pathology. AB - The cuprizone model is a model of de- and remyelination secondary to oligodendrocyte death, likely to be mediated by an inhibition of mitochondrial function. The aim of this study was to characterize histopathological changes associated with de/remyelination in grey and white matter at different disease stages in C57Bl/6 mice after per oral administration of cuprizone. Oligodendrocyte loss, astrocytosis and complement activation was detected in areas of demyelination. Demyelination, astrocytosis and complement activation occurred earlier in the cerebral cortex than in the corpus callosum. There was no perivascular lymphocyte infiltration. Microglia- and macrophage activation was observed in the corpus callosum, but not in the cerebral cortex. After cuprizone exposure was stopped, remyelination was extensive in the corpus callosum, but scarce in the cortex. In conclusion, cortical demyelination and oligodendrocyte loss in the cuprizone model may be due to a direct effect on oligodendrocyte mitochondrial function, as it occurs in the absence of microglial activation. The histopathology of de/remyelination in the cuprizone treated mice show regional heterogeneities which suggest differences in the underlying pathophysiology. Cuprizone-induced demyelination is a relevant model for the study of regional heterogeneity of demyelination and lesion pathology in multiple sclerosis. PMID- 22779689 TI - Clinico-pathological impact of fibroplasia in melanocytic nevi: a critical revision of 209 cases. AB - Fibroplasia is a peculiar stromal reaction at the base of melanocytic lesions, particularly observed in so-called dysplastic nevi. This study evaluates a series of clinico-pathological features in nevi with fibroplasia, their frequence in comparison to usual nevi, and the association of fibroplasia with the risk for the development of melanoma. A total of 209 consecutive nevi showing fibroplasia, belonging to 203 patients, was reviewed. Nevi with fibroplasia were more frequent in men, about half of the lesions belonged to patients aged 11-40 years, and the highest number (52%) were located on the posterior trunk. Lesions 6 mm or greater were 152 (72.73%). Junctional and compound nevi were 52 (24.8%), and 157 (75.2%), respectively. Inflammatory infiltrate was present in 67.8% of cases, melanophages in 56.4%, a lentiginous pattern in 31.1%, focal pagetoid infiltration in three lesions. Nevi with fibroplasia constituted 4.27% of all junctional and compound nevi diagnosed in the same period. A total of 23 patients (11.3%) had a personal history of melanoma. The total number of nevi excised from the 203 patients ranged between 1 and 21, and significantly correlated with the patient's personal history of melanoma (p < 0.001). Fibroplasia is relatively infrequent in melanocytic nevi, it does not appear related to a process of senescence of the lesion, and does not represent a particularly strong predictor of risk of melanoma. PMID- 22779690 TI - Elution of antitransglutaminase antibodies from duodenal biopsies: a novel approach in the diagnosis of celiac disease. AB - Celiac disease (CeD) is a disease more prevalent and multisymptomatic than was earlier recognized. Whereas prompt initiation of gluten-free diet (GFD) is beneficial in relieving the symptoms, an accurate CeD diagnosis is necessary also to avoid years of restricted diet on uncertain grounds. We propose a new diagnostic method, based on elution of deposited antibodies against transglutaminase (anti-tTG) from duodenal biopsies in patients with symptoms and screening serology analyses suggestive of CeD. The eluates were analyzed in a Phadia 250 fluoroimmunoassay, demonstrating elevated concentrations of anti-tTG in CeD patients, corresponding to serology and histopathology findings. In one case histology was inconclusive, displaying only unspecific inflammation, but eluted anti-tTG was positive. This patient has clinically improved following GFD. We conclude that our novel method represents a new tool in the diagnostic work up in CeD. The detection of deposited anti-tTG at the site of inflammation appears to provide a high sensitivity and specificity using a technique that is quick, simple and reliable. Further studies are needed for optimization and elucidation of suitable applications for this elution method. PMID- 22779691 TI - Human mannose-binding lectin inhibits human cytomegalovirus infection in human embryonic pulmonary fibroblast. AB - A limited number of drugs have been used for treatment of human cytomegalovirus (HCMV), all sharing the similar antiviral mechanism of inhibiting virus replication. This study investigates the anti-HCMV activities of mannose-binding lectin (MBL) from blocking virus entry and inhibiting virus spread. Recombinant human MBL was produced in CHO cells and native human MBL was isolated from human serum. A HCMV neutralization test was performed by pre-treating HCMV with each diluted MBL solution. Then the treated HCMV was inoculated onto the human embryonic pulmonary fibroblasts (HELF), which was followed by HCMV-DNA detection, PP65 positivity examination and confocal imaging of the infected cells. To test the activity of MBL in inhibiting viral spreading after viral invasion, HCMV growth inhibition test was performed. The infected cells were incubated with each diluted MBL, every 24 h, the supernatant was tested for HCMV-DNA. After 72 h, cells were collected for HCMV-DNA and PP65 examination. Then the cytopathic effect was observed and cell viability was measured at the 5 days after infection. HCMV neutralization test revealed 10 MUg/mL MBL significantly decreased the HCMV invasion in HELF and the anti-HCMV activity can be blocked by 20 mg/mL mannan. HCMV growth inhibition test indicated that at 48 h after HCMV invasion, the HCMV-DNA level in the culture supernatant with 10 MUg/mL MBL was lower than the control. After 72 h, both the HCMV-DNA levels and PP65 positivity in cells incubated with MBL were reduced. This is the first to report on the anti HCMV activities of MBL by in vitro studies. PMID- 22779692 TI - Human adenovirus infection in children with acute respiratory tract disease in Guangzhou, China. AB - Acute respiratory infections (ARI) are the major worldwide health problem due to associated high morbidity and mortality rates. Adenovirus (Adv) is one of the most common causes of viral ARI, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics. Our aims were to find out the status of Adv infection in children <14 years with ARI, analyze the epidemiology and clinical characteristics among the Adv-infected children in Guangzhou, China, and to provide some basis for the research of Adv. The throat and pharyngeal swabs were collected among the children with acute respiratory tract infections in outpatient department from September 2006 to August 2008. The samples were analyzed by PCR and the sequences were blasted with the sequences of Adv in GenBank. Clinical data were analyzed along with virological data by using appropriate statistical methods. Adv was detected in 25 out of 512 (4.9%) children. The genome types of 23 samples were determined after analysis of the gene sequence. The most prevalent Adv type was species B type 3. Among the patients, 10 were of Ad3 (43.5%), three were of Ad1 (1.3%), five were of species C Ad2 (21.7%), and five were of species E Ad4 (21.7%). A higher incidence of positive results was found during the summer season, thus showing a pattern of seasonality. There exists Adv infection in children with acute respiratory system diseases in Guangzhou area. No significant differences were found among different age groups and gender groups. Co-infections with other respiratory virus were detected in 64% of the Adv positive samples. PMID- 22779693 TI - Randomised clinical trial: alosetron improves quality of life and reduces restriction of daily activities in women with severe diarrhoea-predominant IBS. AB - BACKGROUND: Patients with irritable bowel syndrome with diarrhoea (IBS-D) experience restriction in daily activities and decreased health-related quality of life (QOL). AIM: To investigate effects of alosetron on patient-reported health-related QOL, satisfaction and productivity in women with severe IBS-D. METHODS: A total of 705 women (severe IBS-D, Rome II criteria) randomised to alosetron 0.5 mg QD, 1 mg QD, 1 mg BID, or placebo for 12 weeks were studied. IBSQOL, treatment satisfaction, daily activities, and lost workplace productivity (LWP) were evaluated at randomisation and Week 12. RESULTS: One or more doses of alosetron significantly improved all IBSQOL domains except for sexual function from baseline vs. placebo. The magnitude of IBSQOL changes was consistent with a clinically meaningful effect. Alosetron 0.5 mg QD and 1 mg BID significantly reduced IBS interference with social/leisure activities and LWP from baseline vs. placebo [social/leisure (mean +/-S.E.) days lost: -6.7 +/- 0.8, -7.0 +/- 0.9, P < 0.01; LWP (mean +/- S.E.) h lost: -11.0 +/- 3.3, -21.1 +/- 4.1, P < 0.05 respectively]. Significantly more patients treated with alosetron reported satisfaction vs. placebo. Improvements in IBSQOL, LWP, and treatment satisfaction significantly correlated with global improvement of IBS symptoms. The incidence of adverse events with alosetron was low with constipation being the most commonly reported event. A single case of ischaemic colitis occurred, in a patient receiving alosetron 0.5 mg QD. CONCLUSIONS: In women with severe IBS-D, alosetron treatment, including 0.5 mg QD, resulted in statistically significant and clinically relevant improvements in health-related QOL, restriction of daily activities and treatment satisfaction over placebo. IBS symptom improvement corresponded with positive changes in IBSQOL, LWP and treatment satisfaction. PMID- 22779694 TI - Monoisotopic mass determination algorithm for selenocysteine-containing polypeptides from mass spectrometric data based on theoretical modeling of isotopic peak intensity ratios. AB - Selenoproteins, containing selenocysteine (Sec, U) as the 21st amino acid in the genetic code, are well conserved from bacteria to human, except yeast and higher plants that miss the Sec insertion machinery. Determination of Sec association is important to find substrates and to understand redox action of selenoproteins. While mass spectrometry (MS) has become a common and powerful tool to determine an amino acid sequence of a protein, identification of a protein sequence containing Sec was not easy using MS because of the limited stability of Sec in selenoproteins. Se has six naturally occurring isotopes, 74Se, 76Se, 77Se, 78Se, 80Se, and 82Se, and 80Se is the most abundant isotope. These characteristics provide a good indicator for selenopeptides but make it difficult to detect selenopeptides using software analysis tools developed for common peptides. Thus, previous reports verified MS scans of selenopeptides by manual inspection. None of the fully automated algorithms have taken into account the isotopes of Se, leading to the wrong interpretation for selenopeptides. In this paper, we present an algorithm to determine monoisotopic masses of selenocysteine-containing polypeptides. Our algorithm is based on a theoretical model for an isotopic distribution of a selenopeptide, which regards peak intensities in an isotopic distribution as the natural abundances of C, H, N, O, S, and Se. Our algorithm uses two kinds of isotopic peak intensity ratios: one for two adjacent peaks and another for two distant peaks. It is shown that our algorithm for selenopeptides performs accurately, which was demonstrated with two LC-MS/MS data sets. Using this algorithm, we have successfully identified the Sec-Cys and Sec-Sec cross linking of glutaredoxin 1 (GRX1) from mass spectra obtained by UPLC-ESI-q-TOF instrument. PMID- 22779695 TI - Pasteur's tweezers revisited: on the mechanism of attrition-enhanced deracemization and resolution of chiral conglomerate solids. AB - Insights into the mechanism of attrition-enhanced deracemization and resolution of solid enantiomorphic chiral compounds are obtained by crystal size and solubility measurements and by isotopic labeling experiments. Together these results help to deconvolute the various chemical and physical rate processes contributing to the phenomenon. Crystal size measurements highlight a distinct correlation between the stochastic, transient growth of crystals and the emergence of a single solid enantiomorph under attrition conditions. The rapid mass transfer of molecules between the solution and solid phases under attrition is demonstrated, and the concept of a crystal-size-induced solubility driving force is exploited to overcome the stochastic nature of the crystal growth and dissolution processes. Extension to non-racemizing conditions provides a novel methodology for chiral resolution. Implications both for practical chiral separations and for the origin of biological homochirality are discussed. PMID- 22779696 TI - Dermoscopic findings of pigmented Spitz nevus of the sole. PMID- 22779697 TI - Multiway investigation of interaction between fluorescence labeled DNA strands and unmodified gold nanoparticles. AB - The single stranded DNA can be adsorbed on the negatively charged surface of gold nanoparticles (AuNPs), but the rigid structure of double stranded DNA prevents it from adsorption. Signal of a tagged single stranded DNA will be quenched by the plasmon effect of the AuNP surface after its adsorption. This phenomenon has been used to study the DNA hybridization and interactions of two complementary 21mer oligonucleotides each tagged with a different fluorescent dye in the presence of 13 nm gold nanoparticles. The DNA strands used in this study belong to the genome of HIV. The obtained rank deficient three-way fluorescence data sets were resolved by both PARAFAC and restricted Tucker3 models. This is the first successful application of a multiway chemometric technique to analyze multidimensional nanobiological data. The restricted Tucker3 showed a better performance compared to PARAFAC in resolving the data sets. The advantages of restricted Tucker3 analysis over the unrestricted one, i.e., the limited rotational freedom (more unique results) and better interpretability of the obtained results, were experienced in this study. The resolved excitation, emission, and concentration profiles and specially fluorescence resonance energy transfer (FRET) profiles obtained by restricted Tucker3 were chemically more meaningful than those obtained from PARAFAC. PMID- 22779698 TI - Pharmacogenetics of pain and analgesia. AB - Pain severity ratings and the analgesic dosing requirements of patients with apparently similar pain conditions may differ considerably between individuals. Contributing factors include those of genetic and environmental origin with epigenetic mechanisms that enable dynamic gene-environment interaction, more recently implicated in pain modulation. Insight into genetic factors underpinning inter-patient variability in pain sensitivity has come from rodent heritability studies as well as familial aggregation and twin studies in humans. Indeed, more than 350 candidate pain genes have been identified as potentially contributing to heritable differences in pain sensitivity. A large number of genetic association studies conducted in patients with a variety of clinical pain types or in humans exposed to experimentally induced pain stimuli in the laboratory setting, have examined the impact of single-nucleotide polymorphisms in various target genes on pain sensitivity and/or analgesic dosing requirements. However, the findings of such studies have generally failed to replicate or have been only partially replicated by independent investigators. Deficiencies in study conduct including use of small sample size, inappropriate statistical methods and inadequate attention to the possibility that between-study differences in environmental factors may alter pain phenotypes through epigenetic mechanisms, have been identified as being significant. PMID- 22779699 TI - Similar slow down in running speed progression in species under human pressure. AB - Running speed in animals depends on both genetic and environmental conditions. Maximal speeds were here analysed in horses, dogs and humans using data sets on the 10 best performers covering more than a century of races. This includes a variety of distances in humans (200-1500 m). Speed has been progressing fast in the three species, and this has been followed by a plateau. Based on a Gompertz model, the current best performances reach 97.4% of maximal velocity in greyhounds to 100.3 in humans. Further analysis based on a subset of individuals and using an 'animal model' shows that running speed is heritable in horses (h(2) = 0.438, P = 0.01) and almost so in dogs (h(2) = 0.183, P = 0.08), suggesting the involvement of genetic factors. Speed progression in humans is more likely due to an enlarged population of runners, associated with improved training practices. The analysis of a data subset (40 last years in 800 and 1500 m) further showed that East Africans have strikingly improved their speed, now reaching the upper part of the human distribution, whereas that of Nordic runners stagnated in the 800 m and even declined in the 1500 m. Although speed progression in dogs and horses on one side and humans on the other has not been affected by the same genetic/environmental balance of forces, it is likely that further progress will be extremely limited. PMID- 22779700 TI - The value of EEG-fMRI and EEG source analysis in the presurgical setup of children with refractory focal epilepsy. AB - PURPOSE: In the presurgical evaluation of children and juvenile patients with refractory focal epilepsy, the main challenge is to localize the point of seizure onset as precisely as possible. We compared results of the conventional electroencephalography-functional magnetic resonance imaging (EEG-fMRI) analysis with those obtained with a newly developed method using voltage maps of average interictal epileptiform discharges (IEDs) recorded during clinical long-term monitoring and with the results of the electric source imaging (ESI). METHODS: Simultaneous EEG-fMRI was recorded in nine patients (ages 1.5-17.5 years) undergoing presurgical evaluation. The postoperative outcome and resected area were compared with the following: the localizations of blood oxygen-level dependent (BOLD) signal changes associated with IEDs, which were identified by visual inspection changes using SPM5 software (Analysis I); BOLD signal changes related to IED topography, which was characterized using spike-specific voltage maps of average IED recorded outside the MR scanner during clinical long-term monitoring (Analysis II); as well as results of EEG source analysis based on the distributed linear local autoregressive average (LAURA) algorithm using the Cartool software by Denis Brunet (Analysis III). KEY FINDINGS: All nine patients had postoperative outcome Engel class I-IIb (postoperative time 6-26 months). The analysis I revealed an IED-related area of activation within the resection area in 3 (33%) of 9 patients, analysis II was able to reliably localize the source of epileptic activity in 4 (44%) of 9 patients, and analysis III rendered results concordant with the postoperative resection site in all nine patients. CONCLUSIONS: The localization of seizure onset based on EEG-fMRI may be a useful adjunct in the preoperative evaluation but also has some deficits that impair the reliability of results. In contrast, EEG source analysis is clearly a more credible method for epileptic focus localization in children with refractory epilepsies. It seems likely that the analysis based on IED topography (Analysis II) may increase sensitivity and reliability of EEG-fMRI in some patients. However, the benefit from this innovative method in children is rather limited compared with adults. PMID- 22779701 TI - Molecular identification and characterization of ileal and cecal fungus communities in broilers given probiotics, specific essential oil blends, and under mixed Eimeria infection. AB - Broiler digestive tract fungal communities have gained far less scrutiny than that given corresponding bacterial communities. Attention given poultry associated fungi have focused primarily on feed-associated toxin-producers, yeast, and yeast products. The current project focused on the use of pyrosequencing and denaturing gradient gel electrophoresis (DGGE) to identify and monitor broiler digestive fungal communities. Eight different treatments were included. Four controls were an Uninfected-Unmedicated Control, an Unmedicated Infected Control, the antibiotic bacitracin methylene disalicylate plus the ionophore monensin as Positive Control, and the ionophore monensin alone as a Negative Control. Four treatments were two probiotics (BC-30 and Calsporin) and two specific essential oil blends (Crina Poultry Plus and Crina Poultry AF). All chickens except the Unmedicated-Uninfected Control were given, at 15 days of age, a standard oral Eimeria inoculum of sporulated oocysts. Ileal and cecal digesta were collected at pre-Eimeria infection at 14 days of age and at 7 days post Eimeria infection at 22 days of age. Extracted cecal DNA was analyzed by pyrosequencing to examine the impact of diet supplements and Eimeria infection on individual constituents in the fungal community, while DGGE was used to compare more qualitative changes in ileal and cecal communities. Pyrosequencing identified three phyla, seven classes, eight orders, 13 families, 17 genera, and 23 fungal species. Ileal and cecal DGGE patterns showed fungal communities were clustered mainly into pre- and post-infection patterns. Post-infection Unmedicated-Uninfected patterns were clustered with pre-infection groups demonstrating a strong effect of Eimeria infection on digestive fungal populations. These combined techniques offered added versatility towards unraveling the effects of enteropathogen infection and performance enhancing feed additives on broiler digestive microflora. PMID- 22779702 TI - Discovery of potent inhibitors of human and mouse fatty acid amide hydrolases. AB - Fatty acid amide hydrolase (FAAH, EC 3.5.1.99) is the main enzyme catabolizing endocannabinoid fatty acid amides. FAAH inactivation promotes beneficial effects upon pain and anxiety without the side effects accompanying agonists of type-1 cannabinoid receptors. Aiming at discovering new selective FAAH inhibitors, we developed a series of compounds (5a-u) characterized by a functionalized heteroaromatic scaffold. Particularly, 5c and 5d were identified as extremely potent, noncompetitive, and reversible FAAH inhibitors endowed with a remarkable selectivity profile and lacking interaction with the hERG channels. In vivo antinociceptive activity was demonstrated for 5c, 5d, and 5n at a dose much lower than that able to induce either striatal and limbic stereotypies or anxiolytic activity, thus outlining their potential to turn into optimum preclinical candidates. Aiming at improving pharmacokinetic properties and metabolic stability of 5d, we developed a subset of nanomolar dialyzable FAAH inhibitors (5v-z), functionalized by specific polyethereal lateral chains and fluorinated aromatic rings. PMID- 22779703 TI - Modulation of Leishmania major aquaglyceroporin activity by a mitogen-activated protein kinase. AB - Leishmania major aquaglyceroporin (LmjAQP1) adventitiously facilitates the uptake of antimonite [Sb(III)], an active form of Pentostam(r) or Glucantime(r), which are the first line of defence against all forms of leishmaniasis. The present paper shows that LmjAQP1 activity is modulated by the mitogen-activated protein kinase, LmjMPK2. Leishmania parasites coexpressing LmjAQP1 and LmjMPK2 show increased Sb(III) uptake and increased Sb(III) sensitivity. When subjected to a hypo-osmotic stress, these cells show faster volume recovery than cells expressing LmjAQP1 alone. LmjAQP1 is phosphorylated in vivo at Thr-197 and this phosphorylation requires LmjMPK2 activity. Lys-42 of LmjMPK2 is critical for its kinase activity. Cells expressing altered T197A LmjAQP1 or K42A LmjMPK2 showed decreased Sb(III) influx and a slower volume recovery than cells expressing wild type proteins. Phosphorylation of LmjAQP1 led to a decrease in its turnover rate affecting LmjAQP1 activity. Although LmjAQP1 is localized to the flagellum of promastigotes, upon phosphorylation, it is relocalized to the entire surface of the parasite. Leishmania mexicana promastigotes with an MPK2 deletion showed reduced Sb(III) uptake and slower volume recovery than wild-type cells. This is the first report where a parasite aquaglyceroporin activity is post translationally modulated by a mitogen-activated protein kinase. PMID- 22779704 TI - Thiosulfate dehydrogenase: a widespread unusual acidophilic c-type cytochrome. AB - In this work we identified the gene for the tetrathionate-forming thiosulfate dehydrogenase (TsdA) from the purple sulfur bacterium Allochromatium vinosum by sequence analysis and reverse genetics. The recombinant protein produced in Escherichia coli is a periplasmic, monomeric 25.8 kDa dihaem cytochrome c with an enzyme activity optimum at pH 4. UV-visible and electron paramagnetic resonance spectroscopy indicate methionine (strictly conserved M(222) or M(236)) and cysteine (C(123) ) as probable sixth distal axial ligands of the two haem irons in TsdA. These results place TsdA in the group of c-type cytochromes with an unusual axial histidine-cysteine coordination of the haem iron. These proteins appear to play a pivotal role in sulfur-based energy metabolism. Exchange of C(123) to glycine rendered thiosulfate dehydrogenase inactive, proving the importance of this residue for catalysis. TsdA homologues are present in alpha-, beta-, delta-, gamma- and epsilon-Proteobacteria. Three of these were produced in E. coli and exhibited the expected enzymatic activity. The widespread occurrence of tsdA agrees with reports of tetrathionate formation not only by specialized sulfur oxidizers but also by many chemoorganoheterotrophs that use thiosulfate as a supplemental but not as the sole energy source. PMID- 22779706 TI - Photobiomodulation: poised from the fringes. PMID- 22779705 TI - Effects of sensory feedback in intra-oral target selection tasks with the tongue. AB - PURPOSE: To investigate the effects of visual and tactile intra-oral sensor position feedback for target selection tasks with the tip of the tongue. METHOD: Target selection tasks were performed using an inductive tongue-computer interface (ITCI). Visual feedback was established by highlighting the area on a visual display corresponding to the activated intra-oral target. Tactile feedback was established using a sensor-border matrix over the sensor plates of the ITCI, which provided sensor-position tactile queues via the user's tongue. Target selection tasks using an on-screen keyboard by controlling the mouse pointer with the ITCI's was also evaluated. RESULTS: Mean target selection rates of 23, 5 and 15 activations per minute were obtained using visual, tactile and "none" feedback techniques in the 3rd training session. On-screen keyboard target selection tasks averaged 10 activations per minute in the 3rd training session. Involuntary activations while speaking or drinking were significantly reduced either through a sensor-matrix or dwell time for sensor activation. CONCLUSIONS: These results provide key design considerations to further increase the typing efficiency of tongue-computer interfaces for individuals with upper-limb mobility impairments. PMID- 22779707 TI - Future treatment for COPD: targeting oxidative stress and its related signal. AB - COPD is pathogenically associated with oxidative stress, which originates not only from cigarette smoke, but also from hypoxia, infection, inflammation, and ageing. It is the reason that therapeutic strategies aim at attenuation of oxidative stress, its sources, or intracellular signals and pro-inflammatory network of its downstream. This review discusses the pathogenesis of COPD and its current therapy in viewpoint of oxidative stress and further provides the perspectives for new treatment strategies in COPD and recent patents that could develop into novel therapeutics. PMID- 22779708 TI - Specific immunoglobulin isotypes correlate with disease activity, morphology, duration and HLA association in Pemphigus vulgaris. AB - The molecular basis of disease heterogeneity in autoimmune conditions such as Pemphigus vulgaris is poorly understood. Although desmoglein 3 (Dsg3) has been well established as a primary target of immunoglobulin (Ig) autoantibodies in PV, there remain several questions regarding the overall distribution of anti-Dsg3 Ig subtypes among patient subsets and considerable controversy regarding whether an isotype switch can be observed between phases of disease activity. To systematically address the outstanding questions related to Ig-isotype specificity in PV, we analyzed IgA, IgM, IgG1, 2, 3 and 4 anti-Dsg3 levels by ELISA in 202 serum samples obtained from 92 patients with distinct clinical profiles based on a set of defined variable (activity, morphology, age, duration) and constant (HLA-type, gender, age of onset) clinical parameters, and 47 serum samples from HLA-matched and -unmatched controls. Our findings provide support for earlier studies identifying IgG4 and IgG1 as the predominant antibodies in PV with significantly higher levels in active than remittent patients. We do not see evidence for an isotype switch between phases of disease activity and remission, and both IgG4 and IgG1 subtypes remain elevated in remittent patients relative to controls. We do, however, find IgG4 to be the sole subtype that further distinguishes PV patient subgroups based on different disease morphologies, disease duration, and HLA-types. These data provide further insight into the immune mechanisms responsible for phenotypic expression of disease, and contribute to the broader effort to establish comprehensive immunoprofiles underlying disease heterogeneity to facilitate increasingly specific and individualized therapeutic interventions. PMID- 22779709 TI - Scanning tunneling microscopy reveals single-molecule insights into the self assembly of amyloid fibrils. AB - Many severe diseases are associated with amyloid fibril deposits in the body caused by protein misfolding. Structural information on amyloid fibrils is accumulating rapidly, but little is known about the assembly of peptides into fibrils at the level of individual molecules. Here we investigate self-assembly of the fibril-forming tetrapeptides KFFE and KVVE on a gold surface under ultraclean vacuum conditions using scanning tunneling microscopy. Combined with restrained molecular dynamics modeling, we identify peptide arrangements with interesting similarities to fibril structures. By resolving individual peptide residues and revealing conformational heterogeneities and dynamics, we demonstrate how conformational correlations may be involved in cooperative fibril growth. Most interestingly, intermolecular interactions prevail over intramolecular interactions, and assembly of the phenyl-rich KFFE peptide appears not to be dominated by pi-pi interactions. This study offers interesting perspectives for obtaining fundamental single-molecule insights into fibril formation using a surface science approach to study idealized model systems. PMID- 22779710 TI - Investigation of glucosinolate profile and qualitative aspects in sprouts and roots of horseradish (Armoracia rusticana) using LC-ESI-hybrid linear ion trap with Fourier transform ion cyclotron resonance mass spectrometry and infrared multiphoton dissociation. AB - Within the family of Brassicaceae, an important source of glucosinolates (GLSs) is represented by horseradish ( Armoracia rusticana P. Gaertner, B. Meyer & Scherbius), cultivated for its roots, which are grated fresh or processed into a sauce and used as a condiment. The characteristic pungent flavor of the root depends on the abundance of the bioactive GLS molecules. In crude plant extracts (sprouts and roots) of an accession of horseradish largely diffused in the Basilicata region (southern Italy), which develops many sprouts and produces white, fiery, and sharp-flavored marketable roots, we characterized the GLS profile by LC-ESI-LTQ-FTICR-MS and IRMPD. In sprouts and roots we identified 16 and 11 GLSs, respectively. We confirmed the presence of sinigrin, 4 hydroxyglucobrassicin, glucobrassicin, gluconasturtin, and 4 methoxyglucobrassicin and identified glucoiberin, gluconapin, glucocochlearin, glucoconringianin, glucosativin, glucoibarin, 5-hydroxyglucobrassicin, glucocapparilinearisin or glucobrassicanapin, glucotropaeolin, and glucoarabishirsutain, not previously characterized in horseradish. Of particular note was the presence of the putative 2-methylsulfonyl-oxo-ethyl-GLS. PMID- 22779711 TI - Progress, and yet so much further to go. PMID- 22779713 TI - Mutation analysis of Netrin 1 and HMX3 genes in patients with superior semicircular canal dehiscence syndrome. AB - CONCLUSION: In spite of its absence in the control population, there is questionable evidence for the alteration c.114C->T in the HMX3 gene being implicated in the development of superior semicircular canal dehiscence (SSCD). However, the concept of a complex disease is valid for SSCD and a possible molecular origin can neither be confirmed nor excluded by the results of this study. OBJECTIVES: SSCD was first described in 1998 by Minor et al. While the etiology is not clear, findings from both temporal bone CT and histologic studies suggest a congenital or developmental origin. In recent years, a couple of genes regulating inner ear morphogenesis have been described. Specifically, Netrin-1 and HMX3 have been shown to be critically involved in the formation of the SCC. Molecular alterations in these two genes might lead to a disturbed development of this canal and might represent an explanation for SSCD. METHODS: DNA was extracted from whole blood of 15 patients with SSCD. The coding sequences of Netrin-1 and HMX3 were amplified by PCR and sequenced. RESULTS: One sequence alteration, heterozygous c.114C->T (conservative change without alteration of amino acid) in exon 1 of HMX3, was detected in 2 of 15 patients but not in 300 control chromosomes. The study was supported in part by the Emilia-Guggenheim Schnurr-Foundation, Basel, Switzerland. PMID- 22779714 TI - Occurrence of pharmaceuticals and personal care products in German fish tissue: a national study. AB - German Environment Specimen Bank (GESB) fish tissue samples, collected from 14 different GESB locations, were analyzed for 15 pharmaceuticals, 2 pharmaceutical metabolites, and 12 personal care products. Only 2 pharmaceuticals, diphenhydramine and desmethylsertraline, were measured above MDL. Diphenhydramine (0.04-0.07 ng g(-1) ww) and desmethylsertraline (1.65-3.28 ng g(-1) ww) were measured at 4 and 2 locations, respectively. The maximum concentrations of galaxolide (HHCB) (447 ng g(-1) ww) and tonalide (AHTN) (15 ng g(-1) ww) were measured at the Rehlingen sampling site in the Saar River. A significant decrease in HHCB and AHTN fish tissue concentrations was observed from 1995 to 2008 at select GESB sampling sites (r(2) = 0.69-0.89 for galaxolide and 0.89-0.97 for tonalide with p < 0.003). Galaxolide and tonalide fish tissue concentrations in Germany were ~19* and ~28* lower, respectively, as compared to fish tissue concentrations measured in a United States nationwide PPCP study conducted in 2006. Proximity of the sampling locations to the upstream wastewater treatment plant discharging point and mean annual flow at the sampling location were found to significantly predict galaxolide and tonalide fish tissue concentrations (HHCB: r(2) = 0.79, p = 0.021 and AHTN: r(2) = 0.81, p = 0.037) in Germany. PMID- 22779715 TI - Benefits of spine stabilization with biodegradable scaffolds in spinal cord injured rats. AB - Spine stabilization upon spinal cord injury (SCI) is a standard procedure in clinical practice, but rarely employed in experimental models. Moreover, the application of biodegradable biomaterials for this would come as an advantage as it would eliminate the presence of a nondegradable prosthesis within the vertebral bone. Therefore, in the present work, we propose the use of a new biodegradable device specifically developed for spine stabilization in a rat model of SCI. A 3D scaffold based on a blend of starch with polycaprolactone was implanted, replacing delaminated vertebra, in male Wistar rats with a T8-T9 spinal hemisection. The impact of spinal stabilization on the locomotor behavior was then evaluated for a period of 12 weeks. Locomotor evaluation--assessed by Basso, Beatie, and Bresnahan test; rotarod; and open field analysis--revealed that injured rats subjected to spine stabilization significantly improved their motor performance, including higher coordination and rearing activity when compared with SCI rats without stabilization. Histological analysis further revealed that the presence of the scaffolds not only stabilized the area, but also simultaneously prevented the infiltration of the injury site by connective tissue. Overall, these results reveal that SCI stabilization using a biodegradable scaffold at the vertebral bone level leads to an improvement of the motor deficits and is a relevant element for the successful treatment of SCI. PMID- 22779716 TI - [Severe bleeding one year after a cesarean section caused by placenta increta persistens]. AB - Placenta accreta is a diagnosis, which will gynecologists have to face probably more often, than in previous years. The reason is the increasing number of cesarean sections, one of the most important risk factors. The following case shows, that a placenta accreta not treated primary by hysterectomy, can have consequences even after a longer period. This time the manifestation was a severe bleeding one year after the delivery per cesarean section, which had to be treated by an acute hysterectomy. PMID- 22779717 TI - Laparoscopic reconstructive management of cervical agenesis. AB - OBJECTIVE: To asses the viability of laparoscopic management of cervical agenesis. DESIGN: Case report. SETTING: II. Gynaecology and Obstetrics Dpt. at the University Hospital of F.D. Roosevelt, Banska Bystrica, Slovakia. METHODOLOGY: Diagnostic management and laparoscopic technique. RESULTS: Congenital agenesis of the cervix is a rare anomaly of the inner genital. It may be associated with vaginal aplasia and less frequently with other anomalies like an incomplete fusion of mullerian ducts. Hysterectomy was frequently used to resolve main symptoms with respect to frequent complications associated with reconstructive surgery. Recently we can see a comeback to reconstructive surgery as a result of new medical technologies (new antibiotics and antibacterial sutures). Laparoscopic surgery is considered to be the main approach. The treatment strategy is related to a detailed individual pre-surgery investigation. Success of the surgical treatment is measured by normal menstruation and restored fertility. In this article we report the laparoscopic approach in creating the uterovaginal anastomosis in 20-year old women with cervical agenesis and duplex uterine anomaly and review the treatment options. CONCLUSION: Laparoscopic treatment of cervical agenesis is eligible and might be considered as a first line treatment option. PMID- 22779718 TI - [The psychosocial aspects of perinatal care and their relationship to selected medical interventions and health complications during parturition]. AB - OBJECTIVE: Find association between psychosocial factors of perinatal care and selected childbirth complications and interventions. DESIGN: Original study. SETTING: Department of Psychology, Faculty of Arts and Philosophy, Charles University, Prague. METHODS: Statistical data analysis of questionnaire survey of low-risk parturients (n=657) was carried out. Respondents were divided into experimental groups (EG) according to experienced interventions and complications (hemorrhage, failure to progress, fetal distress, forceps/VEX delivery, caesarean birth, failure to progress followed by caesarean birth, labour acceleration infusion, other infusion, epidural anesthesia, other form of pharmacological analgesia, episiotomy, amniotomy). EG were compared with a control group (CG) of women with no complications and interventions (n=107) in evaluation of psychosocial factors of perinatal care (healthcare provider attitude; control; communication; woman-friendliness of hospital rules) and physical comfort and services, presence of other persons at birth, prevailing emotional reaction and overall satisfaction with maternity care. The interpretation of results draws from qualitative analysis of open-ended question answers. RESULTS: EG and CG differed significantly in control (all EGs scored lower) and healthcare provider attitude evaluation (significantly more negative perception at EGs: hemorrhage, failure to progress, fetal distress, forceps/VEX delivery, labour acceleration infusion, episiotomy). Significant differences were noted also for woman friendliness of hospital rules (lower scores for EGs: hemorrhage, failure to progress, failure to progress followed by caesarean birth) and for presence of other persons at birth. Possible interpretations of the above results are discussed. CONCLUSION: Psychosocial factors of perinatal care constitute important childbirth process determinants, while playing a key role for parturients ability to cope with anxiety and stress connected with childbirth complications and interventions. Beneficial psychosocial climate of a hospital contributes to higher patient satisfaction as well as to lower maternal and neonatal morbidity. PMID- 22779719 TI - [Current state of diagnostics and treatment of overactive bladder in the Czech Republic - five years ago and today]. AB - INTRODUCTION: Overactive bladder (OAB) presents one of the most frequent medical problems among the current adult population, with a significant impact on the quality of life of the affected patients. A questionnaire survey was carried out in 2006, with the aim to assess the level of knowledge regarding the problem of OAB among gynaecologists and urologists in the Czech republic, as well as to evaluate the currently applied methods of OAB diagnostics and treatment. The aim of this work was to perform a repeated survey after five years, and to evaluate, whether there have been any changes achieved in the monitored parameters. MATERIALS AND METHODS: A total of 290 respondents (181 gynaecologists, 109 urologists) were included in the survey in 2006; the study group in 2011 included a total of 285 respondents (180 gynaecologists, 105 urologists). The questionnaire used for the survey in 2011 was identical to the document utilized in the initial survey performed five years ago, with minimal changes. The anonymous questionnaire was designed as "multiple-choice", i.e. with a possible selection from proposed answers; the questions were targeted at the topics of definition, diagnostics and therapy of OAB. The obtained results were processed with the methods of descriptive statistics; the concordance of proportions was evaluated with the Fishers exact test. RESULTS: A total of 114 gynaecologists (63.3%), and 65 urologists (61.9%) were able to determine the correct definition of OAB, which presents a significant increase when compared to 2006 (p<0.0001). The most frequently applied methods of OAB diagnostics were patient history (gynaecologists: 97.8% in 2011 vs. 96.5% in 2006, urologists: 99.0% in 2011 vs. 99.0% in 2006), local examination (gynaecologists: 57.8% vs. 76.4%, urologists: 86.7% vs. 87.2%), bladder diaries (gynaecologists: 62.8% vs. 40.3%, urologists: 79.0% vs. 60.5%), and urine examination (gynaecologists: 71.1% vs. 82.3%, urologists: 96.2% vs. 97.1%). Anticholinergic medication is the first-choice in the OAB treatment in our conditions, which has been confirmed by 146 (81.1%) gynaecologists, and 89 (84.4%) urologists. In cases when the physicians use anticholinergic medication for the treatment of OAB, the first-choice medication is trospium, among both gynaecologists and urologists. In case of failure of the first-choice treatment, twenty-six (14.4%) gynaecologists from the addressed respondents try to continue with a treatment according to their own decision, 154 (85.6%) gynaecologists refer the patient to a specialist. Similarly, a total of 90 (85.7%) urologists try to manage the further course of treatment by their own means, 15 urologists (14.3%) refer the patient to a specialist. CONCLUSION: The level of understanding and awareness about the problem of OAB among the Czech gynaecologists and urologists has significantly improved during the past five years. The applied diagnostic and treatment methods for OAB are being harmonized with the International Continence Society (ICS) recommendations. Taking into consideration the prevalence of OAB among the population, it is desirable to increase the number of clinical departments who deal with the problem of OAB in a complex manner. The remaining significant task lies in the improvement of foreknowledge about the current possibilities and effectiveness of the OAB treatment among the patient population. PMID- 22779720 TI - [Prevalence of anal human papillomavirus infection among women and its relation to cervical HPV infection]. AB - OBJECTIVE: To summarize current knowledge of prevalence, duration and clearance of anal HPV infection among women and its relation to cervical HPV infection. DESIGN: Review article. SETTING: Department of Gynecology and Obstetrics, Hospital Na Bulovce and 1st Medical School of Charles University, Prague; Institute for the Care of Mother and Child, Prague; Gynecologic Oncology Center, Department of Gynecology and Obstetrics, General Faculty Hospital and 1st Medical School of Charles University, Prague. RESULTS: The infection of human papillomavirus (HPV) is strongly associated with the development of anal cancer. Anal HPV infection is common and most anal HPV infections are transient. Women with cervical HPV infection, cervical dysplasia and cervical cancer are at the increased risk. Concurrent anal and cervical HPV infection is most prevalent among the youngest women. By contrast, the prevalence of anal infection alone remains relatively steady in all age groups. Compared with cervical infections, the overall distribution of HPV genotypes in the anus are more heterogeneous and include a greater proportion of nononcogenic types. A high degree of genotype specific concordance is observed among concurrent anal and cervical infections, indicating a common source of infection. Tobacco smoking delays clearance of anal HPV. CONCLUSION: The high degree of genotype-specific concordance suggests that the cervix may be primary source and may serve as reservoir of HPV infection, too. Any type of sexual contact may be a route of transmission, history of anal intercourse is not a condition. The women with HPV related disease of low genital tract form high-risk group for acquisition of anal HPV infection and development of anal carcinoma. PMID- 22779721 TI - [Active cellular immunotherapy of ovarian cancer using dendritic cells]. AB - OBJECTIVE: Overview and comparison of current results of studies dealing with the development and application of anti-cancer vaccines based on dendritic cells in ovarian cancer. DESIGN: Review. SETTING: Department of Obstetrics and Gynaecology Charles University, Prague, 2nd Faculty of Medicine and University Hospital Motol, Department of Immunology 2nd Faculty of Medicine and University Hospital Motol. SUMMARY: Ovarian carcinoma (OVCA) is highly sensitive to chemotherapy; however despite this results from treatment are fairly unsatisfactory. Bearing this in mind, it is important to look for new ways to better understand the immunological mechanisms which could affect reactivation of the disease. It is likely that new knowledge in the field of the immunology of ovarian carcinoma could improve monitoring of the disease and help to ameliorate prognosis of the disease. One strategy in development is creation of anti-OVCA vaccines. Theese vaccines are made by the fusion of dendritic cell (DC) and tumor cells or its parts (NA, peptides). DC are bone-marrow derived leukocytes that are critical in the initiation of T cell mediated immunity. DC are fused to patient-derived ovarian carcinoma cells. The fusion cells induces cytotoxic T cell against autologous OVCA cells. PMID- 22779722 TI - Some aspects of perinatal and maternal mortality in Albania. AB - OBJECTIVE: Evaluation of antenatal care, perinatal mortality, neonatal mortality, maternal mortality, number of births, the incidence of low birth weight infants in Albania. DESIGN OF THE STUDY: Retrospective study. SETTING: Queen Geraldine University Hospital of Tirana, Albania. METHODS: The population of this country is estimated to be approximately 3,2 million and comprises very young people. Twenty five percent of the population is under 15 years of age and 46% is under 25 years [2]. The fertility rate in 2009 was 1.6 children per woman of childbearing age. The urban population accounts for 45% and the rural population for the remaining 55% of the total population [2]. The health care system is spread across nearly the entire territory and is classified as primary (villages and small towns), secondary (several cities) and tertiary (in the capital, University Hospital). Primary health care is provided at 2327 health care units. The chief activity of the family doctors and general practitioners working in such units are focused on providing health care for mother and children. Ten percent of the annual births are delivered at the Maternity Hospital of Tirana (tertiary care) which has 300 beds and another 40 beds particularly for premature infants. More than 50% of the high risk pregnancies from other districts are referred to the Maternity Hospital of Tirana. RESULTS: The annual live births in Albania was in (2010) 33,856. The total perinatal mortality rate is 10,9 per 1000 live births. The total neonatal mortality rate in 2010 was 9.7 per 1000 live births. The early postnatal mortality rate was 6.1 per 1000 births. Number of maternal deaths for 100, 000 live births was 6.0 in 2010. PMID- 22779723 TI - [The surgical procedure of mini-sling antiincontinence procedure AJUST, recommendations and ways of solution of possible special situations]. AB - The objective of our work was to present and summarize the course of a joint meeting of surgeons with experience with AJUST in SUI anti-incontinence treatment. We would like to discuss the operation procedure and its individual steps. Further aim was to determine the optimal operation procedure, step by step, avoiding possible complications in the course of the procedure; simplifying the technique and publishing the recommendations how to solve possible complications in the course of, or after, the operation procedure, was important outcome of the meeting. PMID- 22779724 TI - [Peripartal hysterectomy - review]. AB - Peripartal hysterectomy is one of the life - threatening procedures needed to be performed in an urgent situation. Women at highest risk of peripartal hysterectomy are multiparas, women who had a caesarian delivery in either previous or present pregnancy or women who had an abnormal placentation. This report presents the basic issues and brief review of the major indications of peripartal hysterectomy. It also compares the effectiveness of the selected types of operation. PMID- 22779725 TI - [Trends in vaginal assisted deliveries in the Moravian-Silesian region between the years 2002-2011]. AB - OBJECTIVE: To analyze trends in vaginal assisted deliveries between 2002-2011 in the Moravian-Silesian region, Czech Republic. DESIGN: Retrospective analysis. SETTING: Obstetric facilities in the Moravian-Silesian region, Czech Republic. METHODS: Analysis of data on vaginal assisted deliveries in the obstetric facilities in the Moravian-Silesian region, Czech Republic, between the years 2002-2011. RESULTS: During the analyzed period the use of vacuum extraction rose from 0.11% to 2.44% of all deliveries and the use of forceps declined from 1.54% to 0.24% of all deliveries. The overall frequency of vaginal assisted deliveries increased from 1.65% to 2.87%. The frequency of caesarean section increased from 16% to 24.5%. CONCLUSION: A fundamental change in the trends of vaginal assisted deliveries occurred in the Moravian-Silesian region between 2002 to 2011. There was a significant reduction in the use of forceps and the rise in the use of vacuum extraction with an overall increase in vaginal assisted deliveries. In comparison with the results of the rest of the Czech Republic, the trends in the Moravian-Silesian region are more pronounced. During the analysed period a significant rise of the cesarean section deliveries occurred. PMID- 22779726 TI - Safety and risks associated with screening for chromosomal abnormalities during pregnancy. AB - OBJECTIVES: To assess the risk and safety of screening for chromosomal abnormalities during pregnancy through the assessment of exposure to ultrasound and the fetal loss rate after trans-abdominal amniocentesis (AMNIO) or chorionic villus sampling (CVS). METHODS: It is a retrospective analysis of the fetal loss rate following AMNIO and CVS as a diagnostic tests for chromosomal abnormalities during pregnancy in 1391 singleton pregnancies who attended our clinic from January 2005 to December 2009 (1038 AMNIO and 353 CVS). Pregnancies were followed up to ascertain the fetal loss rate after the procedure which was defined as intrauterine demise or miscarriage before the 24th week of gestation. Review of literature was the method used for assessing the safety of ultrasound during pregnancy. RESULTS: In the group of CVS about 86% of the cases were referred because of a positive screening (screening of chromosomal abnormalities on the bases nuchal translucency and biochemical serum markers (pregnancy-associated plasma protein-A and beta-human chorionic gonadotropin)), test with mean maternal age of 31.7 years and a miscarriage rate of 0.6%. In the group of AMNIO, 40% of the cases were referred because of a positive triple test in the second trimester (screening of chromosomal abnormalities on the bases of biochemical serum markers, alpha-fetoprotein, estriol and total human chorionic gonadotropin in the second trimester of pregnancy). Mean maternal age of 33.2 years and a miscarriage rate of 0.8%. The review of the literature indicates that due to limited amount of information available on some factors (gestational age, duration and number of exposure) during the pregnancy the patient should be exposed to the least ultrasound energy necessary to obtain desired information. CONCLUSION: The fetal loss rate in our study had confirmed that the risk of both procedures is comparable and is 0.8% for AMNIO and 0.6% for CVS. The lower miscarriage rate after CVS could be explained by the theory that placenta is a spongy organ that will expand easily after the procedure allowing better healing than if the needle had been passed through the amnion which is even more stretched by the amniotic fluid, but we are a wear of that the sample size is too small for such a conclusion. According to the available evidence, exposure to diagnostic ultrasonography during pregnancy appears to be safe. PMID- 22779727 TI - [Impact of oxidative stress on male infertility]. AB - Reactive oxygen and nitrogen species (RONS) are necessary for the physiological function of sperm. Its concentration has to be kept on a level without the damage of cells. If this level is overdrawn sperm has pathological effect on many biological structures in the form of oxidative stress. Antioxidants have a key role for keeping of this balance. Oxidative stress is an important factor which causes problems with male fertility. The survey article is complexly concerned with the influence of RONS and antioxidants on male fertility. It outlines some possibilities of treatment and research on this actual issue of assisted reproduction. PMID- 22779728 TI - [The p16INK4A mRNA transcripts estimation in cervical smear with different degrees of cervical dysplasia]. AB - OBJECTIVE: To determine the presence of HPV infection and expression level of p16INK4A mRNA transcripts in cervical smears as adjunct biomarker in detection of cervical intraepithelial neoplasia or cancer. DESIGN: Prospective pilot clinical study assessing clinical utility and validity of ddCt method for qPCR mRNA expression of p16ink4a in comparison to immunohistochemistry. SETTING: Department of Molecular Biology, Department of Obstetrics and Gynecology, Jessenius Medical Faculty, Commenius University, Martin, Slovak Republic. METHODS: Cervical smears (OC) from patients with different cervical lesions (L-SIL, H-SIL, SCA; n=45) and from healthy controls (n=45) were tested for the presence of HPV infection and p16INK4A mRNA transcripts using relative quantification (RQ). Results were compared to H&E and IHC histological findings from biopsies (conization, hysterectomy). RESULTS: HPV 16 was the most frequent finding (53.3%) in the group of subjects with cervical dysplasia. The p16INK4A mRNA expression analysis revealed the slightly reduced expression in L-SIL group, 4-fold increased expression in H-SIL and 10-fold increase in women with SCA when compared to controls. The p16INK4A mRNA expression in OC was present in 30% of L-SIL, 75% of H-SIL and 85.7% of SCA samples, respectively. The test overall sensitivity was 81.48% (95% CI: 61.92-93.7) and specificity 60% (95% CI: 26.24- 87.84) with PPV of 84.62% and NPV of 54.55%. The likelihood ratio (LR) in case of test positivity was 2.04 and for negativity 0.31. The diagnostic accuracy of p16INK4A expression by RQ method in OC smears for prediction of p16 positivity in cervical dysplasia was 66.7% for the L-SIL lesions, 59.5% for H-SIL lesions, and 100% for SCA (r=0.9897, p<0.0913) when compared to IHC p16 positive findings in surgically treated samples. CONCLUSION: The relative quantification is able to determine the level of p16INK4A mRNA transcripts in cervical smear cells with active carcinogenesis nearly at the same level as IHC staining. The advance of biopsy sparing over IHC is qualifying this diagnostic approach for useful candidate in selective management of women with cervical dysplasia looking for cervix preservation or avoiding the unnecessary overtreatment. PMID- 22779729 TI - [Lymphatic mapping in axilla as possible prevention of lymphedema in breast cancer patients - first results of the anatomical study]. AB - OBJECTIVE: Lymphatic mapping is a method to find and preserve upper extremity lymphatics during axillary surgery (axilla clearance and sentinel node biopsy) in breast cancer patients. This may reduce the incidence of lymphedema. We examined on anatomical model, if the lymphatic drainage of the upper extremity is fully separable from the lymphatic drainage of the breast. We further endeavored to find an explanation as to why lymphedema occurs in the upper extremity after sentinel node biopsy in breast carcinoma. DESIGN: Pilot study. SETTING: Oncogynecologic Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague. METHODS: Patent blue dye was injected deep and superficially in arm and breast bilaterally in 9 cadavers. After visualization and precise dissection of the lymphatic vessels and nodes, a record of their routes was made. A scheme of arm and breast lymphatics was constructed. RESULTS: The lymph from arm is drained by 2-4 main afferent collectors. As opposed to cranial and medial collectors, caudal collectors diverged from the axillary vein and entered the caudal axilla. In one case the caudal collector entered a node, which was considered to be the sentinel node of the breast. The other important finding is the demonstration of lymphatic anastomoses that take place between imaged nodes in the caudal axilla, which is the most frequent localization of the breast sentinel lymph node. CONCLUSION: The relationship of lymphatic drainage of the arm and breast are closely related and share connections. These connections represent the main problem, which could explain lymphedema following surgery if damaged. Further studies are necessary to improve understanding of this method and to increase the number of observations. PMID- 22779730 TI - Faulty indwelling urinary catheter detection A defective medical accessory can imitate a typical medical complication. AB - Seldom, the physician faces cases of suboptimal quality of manufacture for various ancillary medical materials. More specifically, a defective medical aid can lend dimensions similar with those of a typical medical complication. Naturally the next step is the investigation and management of complication. The physician will be supposed to have in mind that certain defective medical accessories can be accountable for causing a particular complication. The ultrasonic investigation is a initiative that probably will display the problem and may solve it. In this particular case, unfortunate stitching of indwelling catheter in tissues was not compatible with timing of its insertion at the end of operation. Ultrasonography was rendered possible in the proof of the medical complication absence. Also it guided to the direct and instantaneous resolution of the subject. Key words: indwelling urinary catheter, ultrasonography. PMID- 22779731 TI - [The influence of maternal age, parity, gestational age and birth weight on fetomaternal haemorrhage during spontaneous delivery]. AB - OBJECTIVE: Determine the influence of maternal age, parity, gestational age and birth weight on the volume of fetal erythrocytes which enter the maternal circulation during spontaneous delivery. Determining these parameters would enable improving the guidelines for RhD alloimmunization prophylaxis. DESIGN: Prospective clinical study. SETTING: Department of Obstetrics and Gynecology, University Hospital, Olomouc. METHODS: A total of 2413 examinations were performed. The amount of fetal erythrocytes entering maternal circulation during uncomplicated spontaneous delivery of one fetus was determined by flow cytometry using the BDFACSCanto cytometer (Becton Dickonson International). Laboratory processing: Fetal Cell Count kit (Diagnosis of Feto-maternal transfusion by flow cytometry), IQ Products, IQP-379. Calculation of total volume of fetal erythrocytes entering maternal circulation: Scientific Subcommittee of the Australian and New Zealand Society of Blood Transfusion. Guidelines for laboratory assessment of fetomaternal haemorrhage. 1st ed. Sydney: ANZSBT, 2002: 3-12. RESULTS: The average maternal age when FMH 1.8 ml (95 perc) was 29.4 years vs. 29.1 years when FMH > 1.8 ml, median 30 years in both groups, the difference was not statistically significant (p = 0.501). The average gestational age when FMH 1.8 ml (95 perc) was 275.3 days vs. 276.9 days when FMH > 1.8 ml, median 278 days (39 weeks +5 days) vs. 276 days (39 weeks + 3 days), the difference was not statistically significant (p = 0.849). The average birth weight when FMH 1.8 ml (95 perc) was 3312 g vs. 3353 g when FMH > 1.8 ml, median 3340 g vs. 3330 g, the difference was not statistically significant (p = 0.743). FMH > 1.8 ml (5 perc) was present in 4.1% of primiparas (42/1023), in 4.2% of secundiparas (44/1050) and in 5.3% of multiparas (18/340), the difference was not statistically significant (p = 0.607). The difference in maternal age, parity, gestational age and birth weight were also not statistically significant for fetomaternal hemorrhage FMH > 2.1 ml (2.5 perc), FMH > 2.5 ml (n = 25), FMH > 5 ml (n = 5). CONCLUSION: Maternal age, parity, gestational age and birth weight does not present a risk factor for excessive fetomaternal hemorrhage during spontaneous delivery. PMID- 22779733 TI - Total synthesis of (-)-isoschizogamine. AB - A first asymmetric total synthesis of (-)-isoschizogamine has been accomplished. Our synthesis features the facile construction of the carbon framework of the natural product through a Wagner-Meerwein rearrangement, a tandem metathesis, a stereoselective rhodium-mediated 1,4-addition of an arylboronic acid, and a ring closing metathesis via a hemiaminal ether. PMID- 22779732 TI - Mice overexpressing wild-type human alpha-synuclein display alterations in colonic myenteric ganglia and defecation. AB - BACKGROUND: Prevalent non-motor symptoms of Parkinson's disease (PD) include gastrointestinal motor impairments and advanced stage PD displays pathological aggregates of alpha-synuclein in colonic enteric neurons. We previously showed that 12 months old mice overexpressing human wild type (WT) alpha-synuclein under the Thy1 promoter (Thy1-aSyn) displayed colonic motor dysfunction. We investigated functional gut alterations at earlier ages and histological correlates. METHODS: Defecation, gastric emptying (GE), and immunostaining for alpha-synuclein, peripheral choline acetyltransferase (pChAT), tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), and vasoactive intestinal peptide (VIP) in distal colon myenteric plexuses were assessed in male Thy1-aSyn compared to littermate WT mice. KEY RESULTS: Thy1-aSyn mice aged 2.5-3 or 7-8 months old had 81% and 55% reduction in fecal pellet output, respectively, in the first 15 min of exposure to a novel environment. The reduction remained significant in the older group for 2-h, and subsequent refeeding resulted also in a 60% and 69% reduction of defecation in the first hour, respectively. Thy1-aSyn mice (8-10 months) displayed increased alpha-synuclein in the myenteric plexuses with abundant varicose terminals surrounding pChAT-immunoreactive (ir) neurons, and only a few, nNOS-ir neurons. There were no conspicuous changes in pChAT- and nNOS-ir neurons, or TH- and VIP-ir nerve fibers. Thy1-aSyn mice aged 4-18 months had normal GE. CONCLUSIONS & INFERENCES: The occurrence of over-production of pre synaptic alpha-synuclein in colonic myenteric ganglia several months before the loss of striatal dopamine may provide an anatomical basis for interference with cholinergic neuronal activation, causing an early impairment in defecation to stimuli. PMID- 22779734 TI - The extent of pyrene excimer fluorescence emission is a reflector of distance and flexibility: analysis of the segment linking the LDL receptor-binding and tetramerization domains of apolipoprotein E3. AB - Pyrene is a spatially sensitive probe that displays an ensemble of monomeric fluorescence emission peaks (375-405 nm) and an additional band (called excimer) at ~460 nm when two fluorophores are spatially proximal. We examined if there is a correlation between distance between two pyrenes on an alpha-helical structure and excimer/monomer (e/m) ratio. Using structure-guided design, pyrene maleimide was attached to pairs of Cys residues separated by ~5 A increments on helix 2 of the N-terminal domain of apolipoprotein E3 (apoE3). Fluorescence spectral analysis revealed an intense excimer band when the probes were ~5 A from each other with an e/m ratio of ~3.0, which decreased to ~1.0 at 20 A. An inverse correlation between e/m ratio and the distance between pyrenes was observed, with the probe and helix flexibility also contributing to the extent of excimer formation. We verified this approach by estimating the distance between T57C and C112 (located on helices 2 and 3, respectively) to be 5.2 A (4.9 A from NMR and 5.7 A from the X-ray structure). Excimer formation was also noted to a significant extent with probes located in the linker segment, suggesting spatial proximity (10-15 A) to corresponding sites on neighboring molecules in the tetrameric configuration of apoE. We infer that oligomerization via the C terminal domain juxtaposes the linker segments from neighboring apoE molecules. This study offers new insights into the conformation of tetrameric apoE and presents the use of pyrene as a powerful probe for studying protein spatial organization. PMID- 22779735 TI - Parent-reported participation in children with cerebral palsy: the contribution of recurrent musculoskeletal pain and child mental health problems. AB - AIM: The aim of the study was to explore the contribution of recurrent musculoskeletal pain and mental health to aspects of participation in children with cerebral palsy (CP). METHOD: A total of 105 participants (54 males, 51 females); mean age 14 y (SD 3) were assessed by clinical examination, interview, and parental questionnaires. CP type distribution was as follows: spastic unilateral, 37%; spastic bilateral, 56%; and dyskinetic, 7%. Motor function assessed using the Gross Motor Function Classification System was level I, 33%; level II, 40%; level III, 15%; and level IV/V, 11%. Parents reported child participation using the Assessment of Life Habits, child mental health problems using the Strengths and Difficulties Questionnaire, their own mental health using the General Health Questionnaire, and their socioeconomic status. RESULTS: Recurrent musculoskeletal pain was associated with reduced accomplishment of daily activities (B=-1.22, p=0.02) and social roles (B=-1.17, p=0.03), and with reduced parental satisfaction with the accomplishment of daily activities (B= 1.14, p=0.03) and social roles (B=-1.48, p<0.01). Increasing levels of child mental health problems was associated with reduced accomplishment of daily activities (B=-0.10, p=0.02) and social roles (B=-0.11, p<0.01), and with reduced parental satisfaction with the accomplishment of social roles (B=-0.21, p<0.01). INTERPRETATION: Pain and child mental health should be considered in most participation models in CP. Regarding participation as an objective outcome measure is questionable. PMID- 22779736 TI - When should we expect early bursts of trait evolution in comparative data? Predictions from an evolutionary food web model. AB - Conceptual models of adaptive radiation predict that competitive interactions among species will result in an early burst of speciation and trait evolution followed by a slowdown in diversification rates. Empirical studies often show early accumulation of lineages in phylogenetic trees, but usually fail to detect early bursts of phenotypic evolution. We use an evolutionary simulation model to assemble food webs through adaptive radiation, and examine patterns in the resulting phylogenetic trees and species' traits (body size and trophic position). We find that when foraging trade-offs result in food webs where all species occupy integer trophic levels, lineage diversity and trait disparity are concentrated early in the tree, consistent with the early burst model. In contrast, in food webs in which many omnivorous species feed at multiple trophic levels, high levels of turnover of species' identities and traits tend to eliminate the early burst signal. These results suggest testable predictions about how the niche structure of ecological communities may be reflected by macroevolutionary patterns. PMID- 22779737 TI - Cancer risk in patients with pyogenic liver abscess: a nationwide cohort study. AB - BACKGROUND: There has been no large-scale population-based study on the relationship between pyogenic liver abscesses (PLA) and subsequent cancer risk. AIM: To estimate all cancer risk following a diagnosis of PLA. METHODS: Based on Taiwan's National Health Insurance Research Database, 1257 patients with PLA without prior cancers in the period 1996-2008 were identified and followed-up. The standard incidence ratio (SIR) of each cancer was calculated as the number of observed cancer cases arising among the PLA patients divided by the expected case number of cancer cases according to the national cancer rates. RESULTS: Of the 1257 PLA patients identified, 598 (47.6%) had diabetes mellitus. After a median (+/-s.d.) follow-up of 3.33 +/- 3.45 years, 186 were diagnosed with cancers, including 56 liver cancer, 22 biliary tract cancer and 40 colorectal cancer patients. Patients with PLA had a higher risk of all cancers (SIR, 3.83; 95% CI, 3.30-4.42), liver cancer (SIR, 7.87; 95% CI, 5.94-10.21), biliary tract cancer (SIR, 34.58; 95% CI, 21.67-52.36) and colorectal cancer (SIR, 5.27; 95% CI, 3.76 7.18). The highest SIRs of all cancers, liver cancer, biliary tract cancer and colorectal cancer occurred within 90 days of follow-up (360.82; 95% CI, 278.46 459.91, 257.28; 95% CI, 186.17-346.56, 1153.38; 95% CI 694.08-1801.24, and 52.63; 95% CI 25.2-96.8 respectively). CONCLUSIONS: Pyogenic liver abscesses may herald the onset of cancer, especially hepato-biliary and colon cancer. Further surveys should be conducted for the detection of occult cancers in such patients. PMID- 22779738 TI - Antibiotic resistance of microbial strains isolated from Korean acne patients. AB - Over several decades, topical and systemic antibiotics have been the mainstay of treatment for acne vulgaris. The widespread and long-term use of antibiotics in the treatment of acne has resulted in the spread of resistant bacterial strains and treatment failure. We aimed to examine the bacteriology of acne vulgaris and to evaluate its susceptibility to the antibiotics widely used for acne in Korea. We examined the species of bacteria aerobically and anaerobically isolated from 100 Korean acne patients. Among the bacteria isolated, Staphylococcus epidermidis (36 patients) was the most common, followed by Propionibacterium acnes (30 patients). Eleven strains of P. acnes (36.7%) and 25 strains of S. epidermidis (69.4%) were resistant to one or other of the antibiotics tested. A higher proportion of P. acnes isolates were resistant to clindamycin (30%) and erythromycin (26.7%), than to any other antibiotics tested (P = 0.0003). Some S. epidermidis isolates were resistant to tetracycline and doxycycline in addition to clindamycin and erythromycin. In the previous studies, few strains of P. acnes were found to be resistant to any of the antibiotics, but this study shows that antibiotic-resistant strains have been increasing in Korea acne patients. PMID- 22779739 TI - Application of lipid-based formulations in drug discovery. PMID- 22779740 TI - On seeing the trees and the forest: single-signal and multisignal analysis of periictal intracranial EEG. AB - PURPOSE: Epileptic seizures are associated with a dysregulation of electrical brain activity on many different spatial scales. To better understand the dynamics of epileptic seizures, that is, how the seizures initiate, propagate, and terminate, it is important to consider changes of electrical brain activity on different spatial scales. Herein we set out to analyze periictal electrical brain activity on comparatively small and large spatial scales by assessing changes in single intracranial electroencephalography (EEG) signals and of averaged interdependences of pairs of EEG signals. METHODS: Single and multiple EEG signals are analyzed by combining methods from symbolic dynamics and information theory. This computationally efficient approach is chosen because at its core it consists of analyzing the occurrence of patterns and bears analogy to classical visual EEG reading. Symbolization is achieved by first mapping the EEG signals into bit strings, that is, long sequences of zeros and ones, depending solely on whether their amplitudes increase or decrease. Bit strings reflect relational aspects between consecutive values of the original EEG signals, but not the values themselves. For each bit string the relative frequencies of the different constituent short bit patterns are then determined and used to compute two information theoretical measures: (1) redundancy (R) of single bit strings characterizes electrical brain activity on a comparatively small spatial scale represented by a single EEG signal and (2) averaged pair-wise mutual information with all other bit strings (M), which allows tracking of larger-scale EEG dynamics. KEY FINDINGS: We analyzed 20 periictal intracranial EEG recordings from five patients with pharmacoresistant temporal lobe epilepsy. At seizure onset, R first strongly increased and then decreased toward seizure termination, whereas M gradually increased throughout the seizure. Bit strings with maximal R were always derived from EEG signals recorded from the visually identified seizure onset zone. When compared to the bit strings derived from other EEG signals, their M was relatively smaller. These findings are consistent with a strong but transient occurrence of information-poor, that is, redundant electrical brain activity on a smaller spatial scale, which is particularly pronounced in the seizure-onset zone. On a larger spatial scale, a progressively more collective state emerges, as revealed by increasing amounts of mutual information. SIGNIFICANCE: Information theoretical analysis of bit patterns derived from EEG signals helps to characterize periictal brain activity on different spatial scales in a quantitative and efficient way and may provide clinically relevant results. PMID- 22779741 TI - Molecular and electronic structure of the peptide subunit of Geobacter sulfurreducens conductive pili from first principles. AB - The respiration of metal oxides by the bacterium Geobacter sulfurreducens requires the assembly of a small peptide (the GS pilin) into conductive filaments termed pili. We gained insights into the contribution of the GS pilin to the pilus conductivity by developing a homology model and performing molecular dynamics simulations of the pilin peptide in vacuo and in solution. The results were consistent with a predominantly helical peptide containing the conserved alpha-helix region required for pilin assembly but carrying a short carboxy terminal random-coiled segment rather than the large globular head of other bacterial pilins. The electronic structure of the pilin was also explored from first principles and revealed a biphasic charge distribution along the pilin and a low electronic HOMO-LUMO gap, even in a wet environment. The low electronic band gap was the result of strong electrostatic fields generated by the alignment of the peptide bond dipoles in the pilin's alpha-helix and by charges from ions in solution and amino acids in the protein. The electronic structure also revealed some level of orbital delocalization in regions of the pilin containing aromatic amino acids and in spatial regions of high resonance where the HOMO and LUMO states are, which could provide an optimal environment for the hopping of electrons under thermal fluctuations. Hence, the structural and electronic features of the pilin revealed in these studies support the notion of a pilin peptide environment optimized for electron conduction. PMID- 22779742 TI - Role of the pathotype-specific ACRTS1 gene encoding a hydroxylase involved in the biosynthesis of host-selective ACR-toxin in the rough lemon pathotype of Alternaria alternata. AB - The rough lemon pathotype of Alternaria alternata produces host-selective ACR toxin and causes Alternaria leaf spot disease of the rootstock species rough lemon (Citrus jambhiri) and Rangpur lime (C. limonia). Genes controlling toxin production were localized to a 1.5-Mb chromosome carrying the ACR-toxin biosynthesis gene cluster (ACRT) in the genome of the rough lemon pathotype. A genomic BAC clone containing a portion of the ACRT cluster was sequenced which allowed identification of three open reading frames present only in the genomes of ACR-toxin producing isolates. We studied the functional role of one of these open reading frames, ACRTS1 encoding a putative hydroxylase, in ACR-toxin production by homologous recombination-mediated gene disruption. There are at least three copies of ACRTS1 gene in the genome and disruption of two copies of this gene significantly reduced ACR-toxin production as well as pathogenicity; however, transcription of ACRTS1 and production of ACR-toxin were not completely eliminated due to remaining functional copies of the gene. RNA-silencing was used to knock down the remaining ACRTS1 transcripts to levels undetectable by reverse transcription-polymerase chain reaction. The silenced transformants did not produce detectable ACR-toxin and were not pathogenic. These results indicate that ACRTS1 is an essential gene in ACR-toxin biosynthesis in the rough lemon pathotype of A. alternata and is required for full virulence of this fungus. PMID- 22779743 TI - Effects of daily temperature highs on development of Phakopsora pachyrhizi on soybean. AB - Although considerable information exists regarding the importance of moisture in the development of soybean rust, little is known about the influence of temperature. The purpose of our study was to determine whether temperature might be a significant limiting factor in the development of soybean rust in the southeastern United States. Soybean plants infected with Phakopsora pachyrhizi were incubated in temperature-controlled growth chambers simulating day and night diurnal temperature patterns representative of the southeastern United States during the growing season. At 3-day intervals beginning 12 days after inoculation, urediniospores were collected from each plant and counted. The highest numbers of urediniospores were produced when day temperatures peaked at 21 or 25 degrees C and night temperatures dipped to 8 or 12 degrees C. When day temperatures peaked at 29, 33, or 37 degrees C for a minimum of 1 h/day, urediniospore production was reduced to 36, 19, and 0%, respectively, compared with urediniospore production at the optimum diurnal temperature conditions. Essentially, no lesions developed when the daily temperature high was 37 degrees C or above. Temperature data obtained from the National Climatic Data Center showed that temperature highs during July and August in several southeastern states were too high for significant urediniospore production on 55 to 77% of days. The inhibition of temperature highs on soybean rust development in southeastern states not only limits disease locally but also has implications pertaining to spread of soybean rust into and development of disease in the major soybean-producing regions of the Midwestern and northern states. We concluded from our results that temperature highs common to southeastern states are a factor in the delay or absence of soybean rust in much of the United States. PMID- 22779744 TI - Molecular mapping of the blast resistance genes Pi2-1 and Pi51(t) in the durably resistant rice 'Tianjingyeshengdao'. AB - Tianjingyeshengdao' (TY) is a rice cultivar with durable resistance to populations of Magnaporthe oryzae (the causal agent of blast) in China. To understand the genetic basis of its resistance to blast, we developed a population of recombinant inbred lines from a cross between TY and the highly susceptible 'CO39' for gene mapping analysis. In total, 22 quantitative trait loci (QTLs) controlling rice blast resistance were identified on chromosomes 1, 3, 4, 5, 6, 9, 11, and 12 from the evaluation of four disease parameters in both greenhouse and blast nursery conditions. Among these QTLs, 19 were contributed by TY and three by CO39. Two QTL clusters on chromosome 6 and 12 were named Pi2-1 and Pi51(t), respectively. Pi2-1 was detected under both growth chamber and natural blast nursery conditions, and explained 31.24 to 59.73% of the phenotypic variation. Pi51(t) was only detected in the natural blast nursery and explained 3.67 to 10.37% of the phenotypic variation. Our results demonstrate that the durable resistance in TY is controlled by two major and seven minor genes. Identification of the markers linked to both Pi2-1 and Pi51(t) in this study should be useful for marker-aided selection in rice breeding programs as well as for molecular cloning of the identified resistance genes. PMID- 22779745 TI - Tissue-specific components of resistance to Aspergillus ear rot of maize. AB - Aspergillus flavus and other Aspergillus spp. infect maize and produce aflatoxins. An important control measure is the use of resistant maize hybrids. There are several reports of maize lines that are resistant to aflatoxin accumulation but the mechanisms of resistance remain unknown. To gain a better understanding of resistance, we dissected the phenotype into 10 components: 4 pertaining to the response of silk, 4 pertaining to the response of developing kernels, and 2 pertaining to the response of mature kernels to inoculation with A. flavus. In order to challenge different tissues and to evaluate multiple components of resistance, various inoculation methods were used in experiments in vitro and under field conditions on a panel of diverse maize inbred lines over 3 years. As is typical for this trait, significant genotype-environment interactions were found for all the components of resistance studied. There was, however, significant variation in maize germplasm for susceptibility to silk and kernel colonization by A. flavus as measured in field assays. Resistance to silk colonization has not previously been reported. A significant correlation of resistance to aflatoxin accumulation with flowering time and kernel composition traits (fiber, ash, carbohydrate, and seed weight) was detected. In addition, correlation analyses with data available in the literature indicated that lines that flower later in the season tend to be more resistant. We were not able to demonstrate that components identified in vitro were associated with reduced aflatoxin accumulation in the field. PMID- 22779746 TI - Differential expression of a beta-1,4-endoglucanase induced by diet change in the foliar nematode Aphelenchoides fragariae. AB - We identified and characterized a beta-1,4-endoglucanase, Afr-ENG-1, in the foliar nematode Aphelenchoides fragariae that is differentially expressed when the nematode feeds on fungi or plants. When individuals from hosta plants were transferred to a fungus culture, expression of the enzyme decreased 1,812-fold after five generations on the fungus diet. Afr-eng-1 was readily detected in the genome of 75% of nematodes from the plant population but only in 38% of the diet changed population. The gene cannot be detected in nematodes maintained on fungus for over 100 generations. Diet was also associated with changes in nematode body size and in the severity of symptoms caused on hosta leaves. Plant-diet nematodes caused larger lesions and were longer and thinner than fungus-diet nematodes. Nematodes moved from a plant diet to a fungus diet for five generations had the same body size as the nematodes that had fed on the fungus for 100 generations. Full-length sequences of Afr-eng-1 were obtained and found to encode a glycosyl hydrolase family 5 protein. This is the first beta-1,4-endoglucanase and plant parasitism-related gene described in the genus Aphelenchoides. PMID- 22779747 TI - Parietal cell antibody identified by ELISA is superior to immunofluorescence, rises with age and is associated with intrinsic factor antibody. AB - Parietal cell antibody is a marker for autoimmune gastritis. With identification of gastric H/K ATPase as its molecular target, ELISAs have been introduced. We compared performance of ELISA with immunofluorescence in a retrospective and prospective sera set and correlated the results with intrinsic factor antibody. In 138 retrospective sera selected for positivity or negativity for intrinsic factor antibody, 87 reacted with gastric H/K ATPase by Euroimm ELISA but only 62 reacted by immunofluorescencence.. Similar results were obtained with Inova ELISA with 78 positives that were also positive by Euroimm ELISA. In 161 prospective sera, 29 sera tested positive by ELISA compared to 24 by immunofluorescence. ELISA positive but immunofluoresnce negative sera are bona fide positives because a representative set of 16 sera reacted with both 95kD alpha and 60-90kDbeta subunits of gastric H/K ATPase. ELISA values rose with age regardless of whether immunofluorescence tests were positive or negative. Of 53 sera containing antibody to intrinsic factor, 46/53 (87%) reacted to gastric H/K ATPase by ELISA. Taken together, the data indicates an enhanced detection rate by ELISA over immunofluorescence and validates it as a robust diagnostic assay for parietal cell antibody. As parietal cell antibody marks asymptomatic autoimmune gastritis that may progress to end stage gastric atrophy and haematological complications, and as autoimmune gastritis is associated with autoimmune thyroiditic and type 1 diabetes mellitus, early detection of parietal cell antibody by a sensitive ELISA will enable early follow-up of at risk subjects. PMID- 22779748 TI - Cloning, expression, and antigenicity of 14 proteins from Campylobacter jejuni. AB - Fourteen Campylobacter jejuni genes--porA, cadF, omp18, dnaK, flaC, peb1, peb2, peb3, peb4, ahpC, groEL, tuF, hipO, and Cj0069--were cloned and expressed in Escherichia coli BL21. The recombinant proteins were purified on histidine (His) and glutathione S-transferase (GST) trap columns using the AKTA Explorer 100 System. Recombinant proteins were visualized using sodium dodecyl sulfate polyacrylamide gel electrophoresis and identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The antigenicities of these recombinant proteins were assessed by Western blotting and enzyme-linked immunosorbent assays with anti-C. jejuni immune rabbit sera. Four recombinant proteins, including rGST-PorA, rHis-CadF, rGST-GroEL, and rGST-TuF, demonstrated reactions with both anti-serum and preimmune serum, while rHis-DnaK, rGST-FlaC, rGST-PEB2, rGST-PEB3, rGST-PEB4, and rGST-HipO showed variable antigenicity characteristics to the anti-sera derived from different C. jejuni strains. rHis Omp18, rHis-PEB1, and rGST-AhpC demonstrated universal and specific antigenities with the entire anti-sera panel tested in this present study, while recombinant rGST-Cj0069 and rHis-DnaK did not react with any of the anti-C. jejuni sera tested. In conclusion, rGST-AhpC may be useful as a potential serodiagnostic antigen for C. jejuni infection. PMID- 22779749 TI - On the formation of highly charged gaseous ions from unfolded proteins by electrospray ionization. AB - Electrospray ionization (ESI) of native proteins results in a narrow distribution of low protonation states. ESI for these folded species proceeds via the charged residue mechanism. In contrast, ESI of unfolded proteins yields a wide distribution of much higher charge states. The current work develops a model that can account for this effect. Recent molecular dynamics simulations revealed that ESI for unfolded polypeptide chains involves protein ejection from nanodroplets, representing a type of ion evaporation mechanism (IEM). We point out the analogies between this IEM, and the dissociation of gaseous protein complexes after collisional activation. The latter process commences with unraveling of a single subunit, in concert with Coulombically driven proton transfer. The subunit then separates from the residual complex as a highly charged ion. We propose that similar charge equilibration events accompany the IEM of unfolded proteins, thereby causing the formation of high ESI charge states. A bead chain model is used for examining how charge is partitioned as protein and droplet separate. It is shown that protein ejection from differently sized ESI droplets generates a range of protonation states. The predicted behavior agrees well with experimental data. PMID- 22779750 TI - Hypolithic microbial communities: between a rock and a hard place. AB - Drylands are the largest terrestrial biome on Earth and a ubiquitous feature is desert pavement terrain, comprising rocks embedded in the mineral soil surface. Quartz and other translucent rocks are common and microbial communities termed hypoliths develop as biofilms on their ventral surfaces. In extreme deserts these represent major concentrations of biomass, and are emerging as key to geobiological processes and soil stabilization. These highly specialized communities are dominated by cyanobacteria that support diverse heterotrophic assemblages. Here we identify global-scale trends in the ecology of hypoliths that are strongly related to climate, particularly with regard to shifts in cyanobacterial assemblages. A synthesis of available data revealed a linear trend for colonization with regard to climate, and we suggest potential application for hypoliths as 'biomarkers' of aridity on a landscape scale. The potential to exploit the soil-stabilizing properties of hypolithic colonization in environmental engineering on dryland soils is also discussed. PMID- 22779751 TI - Effects of various heating methods on glucosinolate, carotenoid and tocopherol concentrations in broccoli. AB - The objective of this study was to determine the influence of heating (i.e. boiling, steaming and microwaving) on carotenoid, tocopherol and glucosinolate concentrations in broccoli. We detected five glucosinolate peaks in broccoli representing glucoraphanin, 4-hydroxyglucobrassin, glucobrassicin, 4 methoxyglucobrassicin and neoglucobrassicin. Various heating methods affected the concentrations of nutrients and health-promoting compounds in cruciferous vegetables. The concentrations of five glucosinolates in broccoli significantly decreased after different heating methods, and the rate of decrease was higher with increased cooking time. Cooking broccoli significantly increased the apparent concentrations of lutein, beta-carotene and alpha- and gamma tocopherols. Our results clearly show that health-promoting compounds in broccoli are significantly affected by different heating methods and that all heating treatments reduced glucosinolate concentrations. However, carotenoid and tocopherol concentrations were increased by various heating methods, and a longer heating time increased their extractability. PMID- 22779752 TI - Antidepressants are neuroprotective against nutrient deprivation stress in rat hippocampal neurons. AB - There is ample evidence that depression and stress can be ameliorated through the use of physical exercise and/or antidepressant drugs. Both have been shown to promote neuroprotection against atrophy of dendrites and neuronal death through the activation of pro-survival signaling pathways, such as that of phosphatidyl inositol 3' kinase (PI-3K) and mitogen-activated protein kinase (MAPK). Depriving neurons in culture of several vital nutrients provides a viable model of neuronal stress, trauma or insult that occurs in vivo. Therefore, we sought to evaluate if various antidepressants are indeed neuroprotective in this model of nutrient deprivation stress. In addition, we evaluated if three key pro-survival pathways (PI-3K, MAPK, protein kinase A) are necessary for such neuroprotection. We used quantitative Western blotting to evaluate the immunoreactivity levels of brain derived neurotrophic factor, PI-3K, phospho-protein kinase B (P-Akt), phospho MAPK and phospho-cyclic AMP response element-binding protein, and live/dead cytotoxicity assay to evaluate cell survival. We demonstrate that in the ideal conditions of nutrient supplement, norepinephrine, serotonin and three antidepressants increased all six outcome measures; however, in the absence of such nutrients, only P-Akt levels showed signs of decreasing. In the presence of pro-survival pathway inhibitor, however, five out of the six outcome measures decreased (not P-Akt), relative to those of the ideal conditions of nutrient supplement. Thus, pro-survival pathway integrity, which more directly affects gene expression, is more important than the presence of externally placed nutrients for cell survival. We discuss our results in the context of receptor and pathway cross-talk, indicating that pharmacological rescue of neuronal atrophy/death in the face of mood disorders requires that pro-survival pathways remain intact. PMID- 22779753 TI - Aberrant internal carotid artery causing objective pulsatile tinnitus and conductive hearing loss. AB - Aberrant internal carotid artery (ICA) in the middle ear is a rare, dangerous vascular anomaly and conservative follow-up was usually adopted in most reported cases. Here we report the case of an 8-year-old girl with symptoms of objective pulsatile tinnitus and conductive hearing loss in the right ear. Otoscopic examination, computed tomography, and conventional angiography were performed. An aberrant ICA combined with a 'third mobile window' was suspected preoperatively and confirmed at exploratory surgery of the middle ear. The aberrant ICA was treated, and the pulsatile tinnitus disappeared and hearing recovered after the surgery. This case suggests that surgery is practical to relieve troublesome tinnitus and hearing loss in appropriate cases with aberrant ICA. PMID- 22779754 TI - Rapid screening and guided extraction of antioxidants from microalgae using voltammetric methods. AB - Currently, microalgae draw much attention as a promising source of natural antioxidants to replace synthetic antioxidants for food applications. In this paper, the use of voltammetric techniques as a fast alternative for chemical assays to determine the antioxidant power of microalgal biomass is discussed. It was found that antioxidant activities determined by square wave voltammetry correlate well with the results from other established antioxidant assays, such as Trolox equivalent antioxidant capacity (R(2) = 0.737), ferric reducing antioxidant potential (R(2) = 0.729), and AAPH-induced oxidation of linoleic acid (R(2) = 0.566). Besides yielding quantitative data on the antioxidant activity, square wave voltammetry provides additional information on the antioxidant profile of microalgal biomass as the peak potentials of antioxidant components are determined. Consequently, square wave voltammetry can be used as a tool for optimizing the extraction processes to recover antioxidant components from microalgae. PMID- 22779755 TI - Iterative fragment selection: a group contribution approach to predicting fish biotransformation half-lives. AB - There are regulatory needs to evaluate thousands of chemicals for potential hazard and risk with limited available information. An automated method is presented for developing and evaluating Quantitative Structure-Activity Relationships (QSARs) for a range of chemical properties that can be applied for screening level chemical assessments. The method is an integrated algorithm for descriptor generation, data set splitting, cross validation, and model selection. Resulting QSARs are two-dimensional (2D) fragment-based group contribution models. The QSAR development and evaluation method does not require previous expert knowledge for selecting 2D fragments associated with the chemical property of interest. The method includes information on the domain of applicability (structural similarity to the training set) and estimates of the uncertainty in the QSAR predictions. As a demonstration, the method is applied to generate novel QSARs for fish primary biotransformation half-lives (HL(N)). Results from the new HL(N) QSARs are compared to another 2D fragment-based HL(N) QSAR developed with expert judgment, and the predictive powers of the models are found to be similar. The relative merits and limitations of each method are investigated and the new QSAR is found to make comparable predictions with significantly fewer fragments. A coefficient of determination (R(2)) of 0.789 and a root mean squared error (RMSE) of 0.526 were obtained for the training data set and an R(2) of 0.748 and an RMSE of 0.584 were obtained for the validation data set, along with a concordance correlation coefficient (CCC) of 0.857 showing good predictive power. PMID- 22779756 TI - Looking for new targets: simple coumarins as antibacterial agents. AB - The dramatic worldwide increase of dangerous infections by resistant and multi resistant microbes makes the search of new molecules and new chemical entities an important topic in Medicinal Chemistry. As the ideal drug candidate has not been attained, an intensive search for new and innovative antimicrobials is still needed. A small series of 3-amino/nitrocoumarins without substitutions or substituted by methyl or methoxy groups at different positions were synthesized and evaluated for their antibacterial and antifungal activities against clinical isolates of Staphylococcus aureus, Escherichia coli and Candida albicans strains. Some of these structurally simple molecules exhibited antibacterial activity. The preliminary SAR study showed that the antibacterial activity against E. coli and S. aureus was dependent on the kind and position of the substitution pattern at the coumarin moiety. PMID- 22779757 TI - Enhancement of antitumor effects of a new boron compound combined with ultrasound on the mouse ascites tumor. AB - The use of ultrasound in therapeutic medicine is a developing field. The action of many anticancer agents can be improved with the use of ultrasonic exposure either in vitro or in vivo. Boron-based compounds have shown promising results as chemotherapeutic agents in specific forms of cancer. We synthesized a new boron compound of chloroacetohydroxamic acid, 2-hydroxyamino-oxoethylborate (HAOB). HAOB was used in combination with ultrasound (US) at a frequency of 25 KHz, and inhibitory effects on the growth of mouse ascites tumours were monitored by observing survival time, tumour growth, cell viability and DNA synthesis of treated Ehrlich ascites carcinoma (EAC) cells. 5-Fluorouracil (5-FU) was used as a positive control. The results indicated that HAOB alone produced significant antitumor action whereas combination of US with HAOB or 5-FU produced an extra antitumor action when compared to the actions of HAOB or 5-FU used alone. PMID- 22779758 TI - Transient injury-dependent up-regulation of CD105 and its specific targeting with an anti-vascular anti-mouse endoglin-nigrin b immunotoxin. AB - Endoglin (CD105), a cell-surface co-receptor for transforming growth factor-beta (TGF-beta) superfamily members, is over-expressed in tumor neovasculature and can be targeted with anti-endoglin antibodies, thus becoming an important tool for anti-tumoral therapy. Injury of the mouse tail induced the transient expression of endoglin, this peaking at three days after injury and disappearing six days later. An immunotoxin containing the anti-mouse endoglin rat monoclonal antibody MJ7/18 and the non-toxic ribosome-inactivating protein nigrin b (Ngb) was found to be very active in targeting mouse endoglin in the L929 fibroblast cell line (IC(50) of 4 x 10(-11) M). At that concentration, the immunotoxin lacked unspecific activity. Upon induction of endoglin after injury, the MJ7-Ngb immunotoxin strongly attacked and deranged the injured tail, inducing tissue damage. Such effects were dependent on the age of the animals and were evident in six-week-old mice, but not in eight-month-old mice. Our results indicate that endoglin is up-regulated in newly formed vessels upon injury and can be targeted by the MJ7-Ngb immunotoxin; thus, it could be a useful tool for tumor ablation research. PMID- 22779759 TI - The six-minute walk test in obese youth: reproducibility, validity, and prediction equation to assess aerobic power. AB - PURPOSE: The aim of this study was to assess reproducibility and validity of the 6 minute walk test (6MWT) in obese youth and to develop an equation to predict aerobic power (VO(2max)). METHODS: Fifty-two girls and 45 boys, ages 7-17.8 participated in the study. Three walk tests were administered 1 week apart. Each visit corresponded to a specific test, either an incremental treadmill test, or the 6MWT. The 6MWT was performed on two occasions 1 week apart to assess reproducibility. Treadmill and walk tests were randomly assigned to avoid order effect. RESULTS: Subjects walked 689.4 +/- 98.6 m on the initial 6MWT and 690.4 +/- 98.2 m on the second test. Intraclass correlation coefficient was r = 0.99. The Bland and Altman method also showed good agreement between the two 6MWTs. Stepwise multiple regression determined that distance walked in 6 MWT and BMI are the most significant factors in predicting VO(2max). The prediction equation is VO2 max (ml.kg.min(-1)) = 26.9 + 0.014 * 6 MWT (meters) - 0.38 * BMI (kg/m((2))). CONCLUSIONS: In obese youth, the 6 MWT is a reproducible and valid test for assessing aerobic power. A prediction equation was developed to estimate VO(2)max, using distance walked in 6MWT and BMI. [Box: see text]. PMID- 22779760 TI - First evidence of bacterial biofilms in the anaerobe part of scalp hair follicles: a pilot comparative study in folliculitis decalvans. AB - BACKGROUND: The cause of folliculitis decalvans (FD) remains unknown. We hypothesized that a bacterial biofilm could be involved in its pathogenesis. OBJECTIVE: To assess the presence or not of a bacterial biofilm in the hair roots of the scalp in FD. PATIENTS AND METHODS: Hairs plucked from four patients and three controls were examined by field emission scanning electron microscopy (FESEM) and confocal laser scanning microscopy (CLSM). RESULTS: Bacterial communities organized as biofilms were observed both by FESEM and CLSM in the under infundibular part of hair follicles in all patients and in two of the three controls. In patients and controls, these biofilms were formed exclusively of bacilli of comparable shapes. CONCLUSION: This pilot study provides the first evidence of the presence of bacterial biofilms in the infra infundibular part of human scalp hair follicles. These biofilms were detected both in FD patients and controls, suggesting their ubiquity as a commensal biofilm with a possible pathogenic shift in FD. PMID- 22779762 TI - Determination of serum anti-Mullerian hormone concentrations for the diagnosis of granulosa-cell tumours in mares. AB - REASONS FOR PERFORMING STUDY: Endocrinological assays are important for evaluation of mares with granulosa-cell tumours (GCTs), and our research in mares indicates that anti-Mullerian hormone (AMH) may be a good biomarker for this type of ovarian tumour. OBJECTIVES: To evaluate the use of serum AMH concentrations for endocrine diagnosis of GCTs in mares. METHODS: Archived serum samples (n = 403) previously assayed for determination of serum inhibin, testosterone and progesterone concentrations (GCT panel) were assayed for serum AMH concentrations using a heterologous enzyme-linked immunosorbent assay previously validated by our laboratory. For a subset (n = 44) of these samples, a clinical diagnosis of GCT was confirmed by histopathology. RESULTS: Overall, the sensitivity of AMH (98%) for detection of histologically confirmed GCTs was significantly (P<0.05) greater than that of either inhibin (80%) or testosterone (48%) or the combination of inhibin and testosterone (84%). CONCLUSIONS: Determination of serum AMH concentrations is a useful biomarker for detection of GCTs in the mare. POTENTIAL RELEVANCE: Measurement of serum AMH concentrations can be used for diagnosis of GCTs in the mare. As serum AMH concentrations do not vary significantly during the oestrous cycle or pregnancy, interpretation of these results is not confounded by these physiological states. PMID- 22779763 TI - Half-metallic ferromagnetism in synthetic Co9Se8 nanosheets with atomic thickness. AB - Controlling the synthesis of atomic-thick nanosheets of nonlayered materials is extremely challenging because of the lack of an intrinsic driving force for anisotropic growth of two-dimensional (2D) structures. In that case, control of the anisotropy such as oriented attachment of small building blocks during the reaction process will be an effective way to achieve 2D nanosheets. Those atomic thick nanosheets possess novel electronic structures and physical properties compared with the corresponding bulk samples. Here we report Co(9)Se(8) single crystalline nanosheets with atomic thickness and unique lamellar stacking formed by 2D oriented attachment. The atomic-thick Co(9)Se(8) nanosheets were found to exhibit intrinsic half-metallic ferromagnetism, as supported by both our experimental measurements and theoretical calculations. This work will not only open a new door in the search for new half-metallic ferromagnetic systems but also pave a practical way to design ultrathin, transparent, and flexible paperlike spintronic devices. PMID- 22779761 TI - Characterization of the apoLp-III/LPS complex: insight into the mode of binding interaction. AB - Apolipoproteins are able to associate with lipopolysaccharides (LPS), potentially providing protection against septic shock. To gain insight into the molecular details of this binding interaction, apolipophorin III (apoLp-III) from Galleria mellonella was used as a model. The binding of apoLp-III to LPS was optimal around 37-40 degrees C, close to the LPS phase transition temperature. ApoLp-III formed complexes with LPS from E. coli (serotype O55:B5) with a diameter of ~20 nm and a molecular weight of ~390 kDa, containing four molecules of apoLp-III and 24 molecules of LPS. The LPS-bound form of the protein was substantially more resistant to guanidine-induced denaturation compared to unbound protein. The denaturation profile displayed a multiphase character with a steep drop in secondary structure between 0 and 1 M guanidine-HCl and a slower decrease above 1 M guanidine-HCl. In contrast, apoLp-III bound to detoxified LPS was only slightly more resistant to guanidine-HCl induced denaturation compared to unbound protein. Analysis of size-exclusion FPLC elution profiles of mixtures of apoLp-III with LPS or detoxified LPS indicated a much weaker binding interaction with detoxified LPS compared to intact LPS. These results indicate that apoLp-III initially interacts with exposed carbohydrate regions, but that the lipid A region is required for a more stable LPS binding interaction. PMID- 22779764 TI - [Long-term therapy of idiopathic inflammatory bowel disease]. AB - Crohns disease and ulcerative colitis are chronic inflammatory diseases of the gastrointestinal tract. Both can be treated with medications that induce and maintain remission. The choice of medication is influenced by the balance between drug potency and potential side-effects, previous response to treatment, and the presence of extraintestinal manifestations or complications. After remission has been achieved, the goal of treatment is to maintain the symptom-free status. 5 aminosalicylic acid derivatives have efficacy for maintenance of remission in patients with distal disease. Thiopurines are recommended for the long-term therapy. For the patients who do not have a response to immunosuppressive therapy or cannot tolerate it, anti-TNF-alpha agents are gradually being adopted. Effective in the remission maintenance are thiopurines, infliximab and adalimumab. PMID- 22779765 TI - [Addition of statins into the public water supply? Risks of side effects and low cholesterol levels]. AB - After the discovery of antibiotics, statins, the inhibitors of cholesterol synthesis have been the best-selling prescription drug in the world. These drugs have well documented benefits for cardiovascular disease in many groups of patients at moderate and high cardiovascular risk. US Health authorities are currently pushing for anti-cholesterol drugs to be added to the public water supply. Statins in-depth studies have shown that they can actually have a detrimental effect on the health of people without high cholesterol or heart disorders. Statins should be prescribed only to those patients with heart disease, or who have suffered the condition in the past. Researchers warn that unless a patient is at high risk of the heart attack or stroke, statins may cause more harm than good. PMID- 22779766 TI - [Caecal ligation and puncture in the minipig - a model of sepsis induction]. AB - BACKGROUND: Sepsis belongs among the most serious conditions and animal models of sepsis are the basic tools to investigate the pathophysiological response to this condition. MATERIAL AND METHODS: A total of 16 adult minipigs with identical baseline parameters were randomized into two groups. In the sepsis group (n = 10), sepsis was induced using caecal ligation and puncture (CLP). The control group (n = 6) underwent laparotomy without CLP. Selected clinical and laboratory parameters as well as histological findings between the sepsis and control group were subsequently compared. RESULTS: All animals undergoing CLP developed diffuse peritonitis and sepsis. Compared to the control group, experimental animals showed significant increase of body temperature and heart rate (while) requiring noradrenaline to maintain their perfusion pressure. No significant differences in the monitored biochemical parameters (including C-reactive protein levels) between the two groups were found. Histological findings in organs of experimental animals were consistent with changes of organs seen in sepsis, i.e., centrilobular liver necroses, acute tubular renal necrosis, serous fibrinopurulent exudate, myocardial malacias, and pulmonary edema. CONCLUSION: Experimental caecal ligation with a predefined size of the perforation in the intestinal wall is a suitable model for assessing the pathophysiological changes occurring in the body in sepsis. PMID- 22779767 TI - [Physician and freedom of conscience]. AB - In the arena of bioethics we can find the ideas trying to deny the right to freedom of conscience to physicians. This is an attack upon morality itself. It is therefore urgent to outline the basic knowledge dealing with conscience and to be aware of the fact that violation of conscience leads to breakdown of conscience. The present article deals with Socrates daimonion and his conviction of objective truth as well as with other similar thoughts of great philosophers and theologians in this context: everybody is able to recognize good and evil, some basic knowledge of the common truth exists in the heart of everyone. The feeling of guilt and the capacity to recognize guilt should not be suppressed: the silence of conscience is the greatest tragedy of man. It is quite clear, that the doctor should not agree with the patients every wish, no matter how destructive it is. His own conscience and personal integrity as well as the fact, that the doctor should be the person of integrity, is a more fundamental notion than the respect to autonomy of the patient. Being engaged in killing [euthanasia] serves as an example of bewildering and silencing of conscience. The right to and the importance of physicians freedom of conscience are emphasized in many international documents; the relevant quotations are presented in the text. Key words: conscience, truth, euthanasia, autonomy, conscientious objection. PMID- 22779768 TI - [Smoke-free New Zealand 2025 - utopia or a model?]. AB - New Zealand politicians are aware of the devastating economic and health impact of smoking in their country. The prevalence of that dependence is in New Zealand population aged 15 to 64 years about 20%, but only 4% of the population are "happy" smokers. Therefore, the majority of the population, including smokers, should support plan of gradual effective steps, leading in 2025 to "smoke-free" New Zealand with smoking prevalence in the population below 5%. In the same age group, according to the National Institute of Public Health, the Czech smoking prevalence has remained about 30% for almost ten years and no effective tobacco control legislation is in sight. PMID- 22779769 TI - [Czech paediatric cardiac surgery - history and presence]. AB - The beginnings of the Paediatric Cardiac Surgery in the Czech Republic date back to the period immediately after the end of World War II. Its protagonists were Prof. Emerich Polak from the Surgical Clinic in Prague, Vinohrady, Prof. Jan Bedrna from Surgical Clinic in Hradec Kralove, Prof. Vladislav Rapant from Surgical Clinic in Olomouc and Prof. Vaclav Kafka from the Second Surgical Clinic in Prague. They started with operations of the patent ductus arteriosus, the Blalock-Taussig shunt in cyanotic heart defects and resection of coarctation of the aorta. Operations of congenital heart defects, on the open heart were elaborated namely by cardiosurgeons in Brno, under the leadership of Professor Jan Navratil. On the extension of those methods participated Professor Jaroslav Prochazka in Hradec Kralove and Prof. Vaclav Kafka at the newly opened department of Paediatric surgery in Prague. In the next period, attention of paediatric cardiac surgery was directed at operations of critical congenital heart defects in the smallest children. Palliative operations of the critical heart defects in newborns and infants were first introduced at the clinic of paediatric surgery of the Paediatric University Hospital in Prague. Radical operations of infants and newborns with extra-corporal circulation were elaborated in the Children's heart centre in Prague, Motol. Initiative in the further development of paediatric cardiac surgery was taken over by the Children's heart centre in Prague since its founding in 1977. There was concentrated all medical care of children born with a congenital heart defect in the Czech Republic. This concentration of specialized care at one institution allowed to accumulate extremely large experience with the diagnostics and surgical treatment of congenital heart defects in all age groups with the decrease of patients mortality after operations to 1% even for the smallest children and enabled continuously monitor the quality of life of patients treated for congenital heart defect up to adulthood. It was followed by a system of care for adults with congenital heart defect in cooperation with cardiac surgery departments for adults. Excellent level of paediatric cardiac surgery in the Czech Republic is currently confirmed by comparison of the results in the global database operations of congenital heart defects, led by the European Association for Cardiothoracic Surgery (EACTS). PMID- 22779771 TI - Determination of synthetic by-products and an intermediate in the colour additive D&C Orange No. 5 using high-performance liquid chromatography. AB - Specifications in the US Code of Federal Regulations for the colour additive D&C Orange No. 5 (Colour Index No. 45370:1) limit the levels of the synthetic by products 2-(3,5-dibromo-2,4-dihydroxybenzoyl)benzoic acid (Br2BBA) and brominated resorcinol (Br3R) as well as the level of the intermediate phthalic acid (PhthAc). The present work reports the development and application of a high performance liquid chromatography (HPLC) method for the quantitative determination of these impurities in D&C Orange No. 5 and its lakes. Br2BBA, Br3R and PhthAc were quantified by using five-point calibration curves with data points that ranged from 0.010% to 0.700%, from 0.012% to 0.706% and from 0.006% to 1.383% by weight, respectively. The HPLC method was applied to the analysis of test portions from 11 lots of D&C Orange No. 5 and one lot of D&C Orange No. 5 lake submitted to the US Food and Drug Administration (USFDA) for certification. PMID- 22779770 TI - Design and synthesis of neuroprotective methylthiazoles and modification as NO chimeras for neurodegenerative therapy. AB - Learning and memory deficits in Alzheimer's disease (AD) result from synaptic failure and neuronal loss, the latter caused in part by excitotoxicity and oxidative stress. A therapeutic approach is described that uses NO-chimeras directed at restoration of both synaptic function and neuroprotection. 4 Methylthiazole (MZ) derivatives were synthesized, based upon a lead neuroprotective pharmacophore acting in part by GABA(A) receptor potentiation. MZ derivatives were assayed for protection of primary neurons against oxygen-glucose deprivation and excitotoxicity. Selected neuroprotective derivatives were incorporated into NO-chimera prodrugs, coined nomethiazoles. To provide proof of concept for the nomethiazole drug class, selected examples were assayed for restoration of synaptic function in hippocampal slices from AD-transgenic mice, reversal of cognitive deficits, and brain bioavailability of the prodrug and its neuroprotective MZ metabolite. Taken together, the assay data suggest that these chimeric nomethiazoles may be of use in treatment of multiple components of neurodegenerative disorders, such as AD. PMID- 22779772 TI - Vitamin D for the prevention of stroke incidence and disability: promising but too early for prime time. PMID- 22779773 TI - Platelets are not critical effector cells for the time course of murine passive crescentic glomerulonephritis. AB - Although platelets are well-known effector cells of inflammatory renal disease, clinical studies were not able to establish platelet inhibition as an effective therapy. Our previous studies using Vasodilator stimulated Phosphoprotein- and P2Y1-deficient mice suggested some early, but no long-term effects of platelets in passive crescentic glomerulonephritis. To define the role of platelets for this disease model, passive crescentic glomerulonephritis was induced in 72 C57Bl/6 mice by intraperitoneal injection of sheep anti-rabbit glomerular basement membrane antibody on 2 consecutive days. Platelets were depleted using anti-glycoprotein Ibalpha antibodies (p0p3/p0p4) every 4th day. Mice treated with equal amounts of sterile Phosphate buffered solution or rat-IgG served as controls. Blood, urine, and tissues were harvested on days 3 and 28. Renal tissue sections were evaluated after immunostaining using (semi)quantitative and computer-assisted image analysis. Compared to controls, efficient depletion was achieved as indicated by a markedly prolonged bleeding time and a more than 90% reduction in platelet counts (800/nl vs. 42/nl; P < 0.001). Functional (creatinine-clearance and proteinuria) parameters demonstrated no significant differences between the groups. Neither parameters of renal injury (glomerulosclerosis and fibrosis) nor glomerular/tubulointerstitial matrix expansion (by collagen IV staining), glomerular capillary rarefaction (lectin staining), and the glomerular/tubulointerstitial proliferative response (proliferating cell nuclear antigen) demonstrated any differences between platelet-depleted mice and PBS- or rat-IgG-treated nephritic mice at any time point. Despite effective platelet inhibition/depletion, neither the short- nor long-term course of passive crescentic nephrotoxic nephritis was affected. These data indicate that platelets play a minor role during the time course of this disease model in the mouse. PMID- 22779774 TI - Enhancement of twist angle dependent two-photon activity through the proper alignment of ground to excited state and excited state dipole moment vectors. AB - Herein, we show that the two-photon (TP) transition probability (deltaTP) of o betaine system will reach its maximum value at a twist angle around 65 degrees . However, the potential energy scan with respect to the twist angle between its two rings indicates that the molecule in its ground state is quite unstable at this twist angle. Out of the different possibilities, the one having a single methyl group at the ortho position of the pyridinium ring is found to attain the optimum twist angle between the two rings, and interestingly, this particular substituted o-betaine has larger deltaTP value than any other substituted or pristine o-betaine. The twist angle dependent variation of deltaTP has been explained by employing the generalized-few-state-model formula for 3D molecules. The results clearly reveal that the magnitude of ground to excited state and excited state dipole moment vectors as well as the angle between them are strongly in favor of maximizing the overall deltaTP values at the optimum twist angle. The constructive interference between the optical channels at the optimum twist angle also plays an important role to achieve the maximum deltaTP value. Furthermore, to give proper judgment on our findings, we have also performed solvent phase calculations on all the model systems in nonpolar solvents, namely, cyclohexane and n-hexane, and the results are quite consistent with the gas phase findings. The present study will definitely offer a new way to synthesize novel two-photon active material based on o-betaine. PMID- 22779775 TI - An exon-centric perspective. AB - During the past ten years, remarkable progress has been made in our understanding of the complexity and regulation of alternative splicing. The generation of large datasets of quantitative alternative splicing profiling information has revealed that transcripts from at least 95% of multi-exon human genes undergo alternative splicing, and that thousands of exons in mammalian transcriptomes are subject to striking regulatory patterns. Together with advanced computational methods, these datasets have enabled the inference of a predictive code for tissue-dependent alternative splicing. This code has further provided new insight into splicing regulatory mechanisms. Collectively, these approaches are revealing the existence of discrete networks of exons that are coordinately regulated in diverse biologically normal and disease contexts. A major challenge ahead is to systematically determine the functions of exons comprising these exon networks as well as the factors and mechanisms responsible for their regulation. This perspective provides an account of progress in these areas and also discusses future avenues of exon-centric exploration. PMID- 22779776 TI - The adverse event profile of lacosamide: a systematic review and meta-analysis of randomized controlled trials. AB - PURPOSE: Defining the tolerability and safety profile of recently marketed antiepileptic drugs, such as lacosamide (LCM), is a prerequisite for their optimal utilization in clinical practice. We aimed to identify any adverse event (AE) associated with LCM treatment by conducting a systematic review and meta analysis of all available randomized controlled trials (RCTs). We also evaluated the association of serious AEs with LCM, the proportion of study withdrawals due to intolerable AEs at different LCM doses, and whether the tolerability profile of LCM differs according to the disorder in which it was investigated. METHODS: We searched MEDLINE and Cochrane CENTRAL to May 2011 for LCM RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebo-controlled, double-blind RCTs and investigated the therapeutic effects of oral LCM in adults with any condition. AEs were assessed for their association with LCM after identification/exclusion of synonyms, rare AEs, and non-assessable AEs. We used risk differences to evaluate the association of any (99% confidence intervals [CIs]) or serious AEs (95% CIs) with LCM and to investigate dose-response relationships of identified AEs. KEY FINDINGS: Ten RCTs (three in pharmacoresistant epilepsy, four in neuropathic pain, one in migraine, one in fibromyalgia, and one in knee osteoarthritis) were included in our study. Their duration varied from 12-18 weeks. The total number of patients included was 3,148. No serious AE was significantly associated with LCM treatment. Of 21 identified AEs, 11 (52%) were found to be significantly associated with LCM. The number of AEs significantly associated with LCM increased with increasing dose: one at 200 mg/day (dizziness); six at 400 mg/day (dizziness, vertigo, abnormal coordination, abnormal vision, nausea, and vomiting); nine at 600 mg/day (dizziness, vertigo, ataxia, balance disorder, diplopia, fatigue, nausea, vomiting, and tremor). The proportion of AE-related study withdrawals also significantly increased with increasing dose. LCM AEs tended to occur more frequently in patients with drug resistant epilepsy compared with patients with other disorders. SIGNIFICANCE: A range of AEs suggestive of vestibulocerebellar dysfunction is significantly associated with LCM treatment and their incidence increases with increasing doses. PMID- 22779777 TI - Mode recognition in UV resonance Raman spectra of imidazole: histidine monitoring in proteins. AB - The imidazole side-chains of histidine residues perform key roles in proteins, and spectroscopic markers are of great interest. The imidazole Raman spectrum is subject to resonance enhancement at UV wavelengths, and a number of UVRR markers of structure have been investigated. We report a systematic experimental and computational study of imidazole UVRR spectra, which elucidates the band pattern, and the effects of protonation and deprotonation, of H/D exchange, of metal complexation, and of addition of a methyl substituent, modeling histidine itself. A consistent assignment scheme is proposed, which permits tracking of the bands through these chemical variations. The intensities are dominated by normal mode contributions from stretching of the strongest ring bonds, C(2)N and C(4)C(5), consistent with enhancement via resonance with a dominant imidazole pi-pi* transition. PMID- 22779778 TI - Separation of polypeptides by isoelectric point focusing in electrospray-friendly solution using a multiple-junction capillary fractionator. AB - We introduce an online multiple-junction capillary isoelectric focusing fractionator (OMJ-CIEF) for separation of biological molecules in solution by pI. In OMJ-CIEF, the separation capillary is divided into seven equal sections joined with each other via tubular Nafion membrane insertions. Each junction is communicated with its own external electrolytic buffer which is used both to supply electrical contact and for solvent exchange. The performance of the fractionator was explored using protein and peptide samples covering broad pI range. Separation was achieved in ionic and ampholytic buffers, including ammonium formate, ammonium hydroxide, histidine, and arginine. By maintaining electric potential across upstream segments of the capillary after the focusing stage, selective release of downstream analyte fractions could be achieved. The selective release mode circumvents the problem of peak broadening during mobilization and enables convenient comprehensive sampling for orthogonal separation methods. Using single-component ampholyte buffers with well-defined pI cutoff values, controlled separation of protein mixture into basic and acidic fractions was demonstrated. The device is cheap and easy to fabricate in-house, simple in operation, and straightforward in interfacing to hyphened analytical platforms. OMJ-CIEF has a potential of becoming a practical add-on unit in a wide range of bioanalytical setups, in particular as a first-dimension separation in mass spectrometry based proteomics or as a preparative tool for analyte purification, fractionation, and preconcentration. PMID- 22779779 TI - Anti-tumour necrosis factor treatment of inflammatory bowel disease in liver transplant recipients. AB - BACKGROUND: Ulcerative colitis (UC) and Crohn's disease can sometimes relapse and be refractory to standard treatment following orthotopic liver transplantation (OLT) despite post-transplantation immunosuppressive therapy. AIM: To evaluate the efficacy and safety of anti-tumour necrosis factor (anti-TNF) agents for the management of IBD following OLT. METHODS: We reviewed the records of patients with a diagnosis of IBD who underwent OLT at Mayo Clinic Rochester between 1985 and 2009. Patients were included if they had received anti-TNF therapy post-OLT. Clinical response was defined as a physician's assessment of improvement after 12 weeks of anti-TNF usage, and mucosal healing was defined as the absence of ulcerations on follow-up endoscopy. RESULTS: The median age of the eight study patients was 42.0 years and 37.5% were female patients. All had been diagnosed with IBD prior to OLT (UC in three and Crohn's disease in five). Indication for OLT was cirrhotic stage primary sclerosing cholangitis (PSC), and three concomitantly had cholangiocarcinoma. Clinical response was demonstrated in seven of eight patients (87.5%) and mucosal healing was demonstrated in three of seven (42.9%). Four infections (oral candidiasis, Clostridium difficile colitis, bacterial pneumonia and cryptosporidiosis) in three patients were reported. One patient developed an Epstein-Barr virus-positive post-transplant lympho proliferative disorder. One death occurred due to complications from recurrent PSC. CONCLUSIONS: Starting Anti-TNF therapy following orthotopic liver transplantation appears to be a potential option for inflammatory bowel disease management. Additional studies are needed, however, to confirm these findings and to further assess risks associated with this treatment strategy. PMID- 22779780 TI - The relationship between dietary advanced glycation end products and indicators of diabetes severity in Mexicans and non-Hispanic whites: a pilot study. AB - Diet is an important source of exogenous advanced glycation end products (AGEs). Dietary AGEs content depends on nutrient composition and on the way food is processed/cooked. The objective of our study was to compare AGEs intake of two different ethnic groups (Mexicans and non-Hispanic whites) with type 2 diabetes mellitus (DM) and to study the relationship between dietary AGEs and diabetes related complications. Complications were self-reported by subjects (n = 65) and categorized according to a published DM disease severity index as low risk or moderate-high risk. Dietary records for 10 days were used to estimate dietary AGEs from a published food table. Non-Hispanic whites had higher intake of dietary AGEs (natural logarithm was used, LogAGEs) when compared with Mexicans, which was consistent with their higher intake of saturated fat. In addition, for each unit increase in the LogAGEs, a participant was 3.7 times more likely to have moderate-high risk for cardiovascular disease. PMID- 22779781 TI - Maternal morbidity during childbirth hospitalization in California. AB - OBJECTIVE: To determine the incidence and risk factors for maternal morbidity during childbirth hospitalization. METHODS: Maternal morbidities were determined using ICD9-CM and vital records codes from linked hospital discharge and vital records data for 1,572,909 singleton births in California during 2005-2007. Socio demographic, obstetric and hospital volume risk factors were estimated using mixed effects logistic regression models. RESULTS: The maternal morbidity rate was 241/1000 births. The most common morbidities were episiotomy, pelvic trauma, maternal infection, postpartum hemorrhage and severe laceration. Preeclampsia (adjusted odds ratio [AOR]: 2.96; 95% confidence interval 2.8,3.13), maternal age over 35 years, (AOR: 1.92; 1.79,2.06), vaginal birth after cesarean, (AOR: 1.81; 1.47,2.23) and repeat cesarean birth (AOR: 1.99; 1.87,2.12) conferred the highest odds of severe morbidity. Non-white women were more likely to suffer morbidity. CONCLUSIONS: Nearly one in four California women experienced complications during childbirth hospitalization. Significant health disparities in maternal childbirth outcomes persist in the USA. PMID- 22779782 TI - The conceptualization of participation. PMID- 22779784 TI - Round window vibroplasty: long-term results. AB - CONCLUSIONS: The round window (RW) approach in the use of the Vibrant Soundbridge((r)) (VSB) is a safe and effective treatment of conductive and mixed hearing losses for a period of more than 3 years of device use. OBJECTIVE: To investigate the long-term safety and efficacy as well as user satisfaction of patients with conductive and mixed hearing losses implanted with the VSB using RW vibroplasty. METHODS: Twelve patients with conductive and mixed hearing losses were evaluated after 40 months of daily VSB use. Safety was assessed by evaluating reports of postoperative medical and surgical complications as well as by changes in bone conduction hearing thresholds. Efficacy outcome measures included aided and unaided hearing thresholds, speech recognition in quiet and in noise and subjective benefit questionnaires. RESULTS: The safety results revealed no significant medical complications. One subject experienced sudden hearing loss after 18-24 months of device use, but still continues to wear the device to her satisfaction. With regard to efficacy, there were no significant changes from short- to long-term results in aided word understanding, functional gain or speech recognition threshold, suggesting that the outcomes are stable over time. Subjective questionnaires revealed either the same or better results compared with the short-term data. PMID- 22779785 TI - Methylmercury cycling in High Arctic wetland ponds: sources and sinks. AB - The sources of methylmercury (MeHg; the toxic form of mercury that is biomagnified through foodwebs) to Arctic freshwater organisms have not been clearly identified. We used a mass balance approach to quantify MeHg production in two wetland ponds in the Lake Hazen region of northern Ellesmere Island, NU, in the Canadian High Arctic and to evaluate the importance of these systems as sources of MeHg to Arctic foodwebs. We show that internal production (1.8-40 ng MeHg m(-2) d(-1)) is a much larger source of MeHg than external inputs from direct atmospheric deposition (0.029-0.051 ng MeHg m(-2) d(-1)), as expected. Furthermore, MeHg cycling in these systems is dominated by Hg(II) methylation and MeHg photodemethylation (2.0-33 ng MeHg m(-2) d(-1)), which is a sink for a large proportion of the MeHg produced by Hg(II) methylation in these ponds. We also show that MeHg production in the two study ponds is comparable to what has previously been measured in numerous more southerly systems known to be important MeHg sources, such as temperate wetlands and lakes, demonstrating that wetland ponds in the High Arctic are important sources of MeHg to local aquatic foodwebs. PMID- 22779786 TI - Inhibition of secreted phospholipase A2 by proanthocyanidins: a comparative enzymological and in silico modeling study. AB - Secreted phospholipase A2 (PLA2) plays a critical role in mobilizing arachidonic acid in phospholipids. We have previously reported that PLA2 is inhibited by B type proanthocyanidins (PaCs). To further understand the inhibitory activity of these compounds, we compared the inhibitory potency of B-type PaCs to that of A type PaCs and modeled them with PLA2 using in silico techniques. The B-type trimer and tetramer inhibited PLA2 (IC50 = 16 and 10 MUM). The A-type compounds were less potent (18-35% inhibition at 50 MUM). The active site of PLA2 lies in a hydrophobic tunnel. Modeling studies revealed that the B-type PaCs occupy this tunnel and are stabilized by a number of van der Waals interactions. The result is reduced substrate access to the active site. The A-type compounds can occupy this tunnel only by shifting the N-terminal loop outward. Our data provide a structural basis to screen additional PaCs for anti-PLA2 activity. PMID- 22779787 TI - Dammarane glycosides from the root of Machilus yaoshansis. AB - Nine new dammarane triterpene glycosides (1-3 and 8-13) and 12 known analogues have been isolated from an ethanol extract of the roots of Machilus yaoshansis. Compounds 1-7 have an uncommon 20,23-dihydroxydammar-24-en-21-oic acid-21,23 lactone moiety that was previously reported in compounds isolated from Gynostemma pentaphyllum. The configurations of the lactone moieties in 1-3 were determined by comparison of the experimental ECD spectra of 1-3 and the hydrolysates, 1a and 1b, with the corresponding calculated ECD spectra. On the basis of NMR and ECD data analysis of 1-7, the previously reported C-20 and C-23 configurations of 4-7 and related derivatives from Gynostemma pentaphyllum were revised. In addition, the application of NMR data and Cotton effects to the determination of the relative and absolute configurations of the gamma-lactone moiety in 3beta,20,23 trihydroxydammar-24-en-21-oic acid-21,23-lactone derivatives is discussed. PMID- 22779788 TI - Synthesis, leptospirocidal activity and QSAR analysis of novel quinoxaline derivatives. AB - A simple and efficient method has been developed for the synthesis of series of N Mannich bases of (E)-3- (phenylimino/4-chlorophenylimino)-2,3-dihydro-1-[(N substituted piperazinyl) methyl]quinoxaline-2-(1H)-one 3a-f and 4a-f. The requisite 2a and 2b were obtained by reaction between quinoxaline-2,3-dione 1 and aniline/p-chloroaniline. These compounds underwent NMannich reaction with various substituted piperazines to yield (title compounds 3a-f and 4a-f respectively. Structures of synthesized compounds were confirmed by spectral studies (IR, 1H NMR, 13C NMR and Mass) and elemental analysis. All the synthesized compounds were screened for in vitro leptospirocidal activty against Leptospira interrogans. The potent compounds 4a, 4b and 4c which showed maximum activity during in vitro studies were subjected to in vivo studies. The inhibitory activity of enzymes carboxypeptidase and transpeptidase, in leptospirosis by the synthesized compounds were determined. 3D-QSAR studies model developed showed the need for more hydrophobic and less steric groups as substituent groups to enhance the in vitro activity. PMID- 22779789 TI - Synthesis of 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2- a] pyrimidin-4-one derivatives as antibacterial agents. AB - A series of novel 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2 a]pyrimidin-4-one aliphatic/ aromatic/ heterocyclic amine derivatives were synthesized in good yield. The synthesized compounds were characterized by 1H NMR, FTIR and elemental analysis. All the synthesized compounds were screened for their in vitro antibacterial activity by agar well diffusion and micro dilution method against standard strains of Gram-Positive (Bacillus Subtilis MTCC 121 and Staphylococcus epidermidis 435), and Gram-negative (Xanthomonas Campestris 7903 and Pseudomonas aeruginosa MTCC 7908) bacteria. Compounds with substituted heterocyclic piperazine moiety showed good activity. In particular, compound 6i showed two fold better activity compared to the standard drug Strepyomycin sulphate. PMID- 22779790 TI - Molecular features for antitrypanosomal activity of thiosemicarbazones revealed by OPS-PLS QSAR studies. AB - A quantitative structure-activity relationship analysis was employed to explore the relationship between the molecular structure of thiosemicarbazone analogues and the inhibition of the cysteine protease cruzain, a validated target for Chagas' disease treatment. A data set containing 53 thiosemicarbazone derivatives was used to produce a quantitative model for activity prediction of unknown compounds. Several electronic descriptors were obtained through DFT calculations, along with a large amount of Dragon descriptors. The ordered predictor selection (OPS) algorithm was employed to select the most relevant descriptors to perform PLS regressions. With this procedure, significant correlation coefficients (r(2) = 0.85, q(2) = 0.78) were achieved. Furthermore, predicted values for an external test set are in good agreement with the experimental results, indicating the potential of the model for untested compounds. Additional validation tests were carried out, indicating that a robust and reliable model was obtained to be used in the design of new thiosemicarbazones with improved cruzain inhibition potential. PMID- 22779791 TI - Discovering the binding modes of natural products with histone deacetylase 1. AB - Histone deacetylases (HDACs) belong to a superfamily of enzymes responsible for deacetylating the Nterminal tails of histones. Overproduction of HDACs has a significant role in tumorigenesis. Accordingly, inhibition of HDACs has been widely applied for cancer therapy. It is encouraging that some natural products showed promising potency and selectivity against HDACs. In order to uncover their keys of good performance, the binding patterns of several natural HDAC1 inhibitors in the active site of HDAC1 were navigated by homology modeling, docking and molecular dynamic simulations. Evaluation of the binding poses allowed us to recognize the roles of different residues around the active site, and to understand the core features in the structure of the inhibitor molecule. Hydrophobic and H-bond interactions formed between the ligand and residues were discovered to make significant contributions to the ligand-receptor binding. Finally, the structural requirement of inhibitors for binding to HDAC1 was well proposed. Our results are beneficial to the design of potent HDAC1 inhibitors. PMID- 22779792 TI - Design, synthesis, pharmacological evaluation and descriptor based similarities study of N,N-diphenyl-2-[4-(substituted phenyl)piperazin-1-yl]acetamides as potential antipsychotics. AB - A series of novel N,N-diphenyl-2-[4-(substituted phenyl)piperazin-1-yl]acetamides was designed, synthesized and evaluated for anti-dopaminergic activity, anti serotonergic activity and catalepsy induction studies in mice as an approach to novel potential antipsychotic agent. Antipsychotic activity of these compounds in terms of blocking of dopaminergic transmission was evaluated by their ability to inhibit apomorphine induced climbing behavior in mice and antiserotonergic activity of synthesized compounds was assessed by studying inhibition of 5-HTP induced head twitches. All the synthesized compounds were found to exhibit anti dopaminergic and anti-serotonergic activity in behavioral models. The compound 3f showed better antipsychotic potential among the different synthesized compounds. The descriptor based similarities study for blood brain permeation established a good similarity between the synthesized compounds with standard atypical antipsychotics. PMID- 22779793 TI - Design, synthesis and antimicrobial properties of novel 3,3a,4,5,6,7- hexahydroindazole and arylthiazolylpyrazoline derivatives. AB - A remarkable diastereoselective synthesis of some novel arylthiazolyl pyrazoline derivatives 3(a-l) is displayed which were evaluated for their in vitro antimicrobial activities. In particular, compounds 3e, 3g & 3l (MIC 12.5 MUg /ml) showed good activity against S. aureus and compounds 3b & 3j (MIC 12.5 MUg / ml) against B. subtilis. Compounds 3g, 3i, 3j (MIC 12.5 MUg/ ml) and 3l (MIC 6.25 MUg / ml) also displayed excellent antifungal activity against C. albicans. Of all the synthesized compounds, 3g and 3e exerted a wide range of antibacterial activities against entire tested gram positive (S. aureus and B. subtilis) and gram negative (E. coli and P. aeruginosa) bacterial strain except P. aeruginosa. PMID- 22779794 TI - Design, synthesis and antihistamine evaluations of several N-hydroxyalkyl desloratadine analogues. AB - Several N-hydroxyalkyl desloratadines and N-methoxyl ethyl desloratadine were prepared and evaluated for H1 antihistamine activity. The effects on isolated ileum smooth muscle tension in guinea pigs in vitro and asthma-relieving effects on the histamine-induced asthmatic reaction in guinea-pigs in vivo were examined. Most of them exhibited satisfactory H1 antihistamine activity and were obviously more potent than loratadine. Among these, Compound 3, N-(3-hydroxy)propyl desloratadine was the most active one. And it was chosen as a candidate for evaluation of acute toxicity (LD(50)= 0.876(0.784-0.980) g/kg), significantly superior to that of desloratadine (LD(50)=0.353 g/kg). Meanwhile, the experimental results demonstrated that the oxygen atom in the side carbon chain is crucial for enhancing the antihistamine activities. PMID- 22779795 TI - Design, synthesis and anticonvulsant activity evaluation of 7-substituted-[1,2,4] triazolo[4,3-f]pyrimidine derivatives. AB - In this study, a novel series of 7-substituted-[1,2,4]triazolo[4,3-f]pyrimidine derivatives was synthesized as potential anticonvulsant agents. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The pharmacological results showed that the compound 3i (7-(4-chlorophenoxy) [1,2,4]triazolo[4,3-f]pyrimidine) was among the most active agent with median effective dose (ED(50)) value of 34.7 mg/kg, median toxicity dose (TD(50)) of 262.9 mg/kg, and providing a protective index (PI=TD(50)/ED(50)) value of 7.6. The compound 3i also showed oral activity against MES-induced seizures and lower oral neurotoxicity. The compound 3i demonstrated antagonistic activity against seizures induced by PTZ, ISN, 3-MP and thiosemicarbazide. PMID- 22779797 TI - On the affinity and specificity of quercetin for DNA. AB - The potential of quercetin (QUE), being a member of the whole family of structurally different flavonoids, to serve as an anti-tumor agent has been recognized, but not fully understood. The interactions between DNA and a series of the flavonoids have so far been mainly investigated using a variety of experimental techniques. Herein, the specificity of QUE for DNA is explored using sophisticated density functional theory (DFT) methods employed to generate the optimized structure of QUE in complex with adenine (A), guanine (G), thymine (T) and cytosine (C), respectively. As far as a preference of QUE is concerned, structural and energetic as well as NMR chemical shift arguments clearly indicate a highest for G and a lowest for C. This observation is further substantiated by analyzing the binding modes of QUE docked in a quadruplex receptor structure of DNA and in a duplex receptor structure of DNA. Among all possible single point mutations of the DNA quadruplex and duplex residues, several critical ones causing a conspicuous stabilizing effect on the original complexes of QUE with the DNA receptors are identified. Consequently, several fundamental standpoints shedding new light on the molecular mechanisms underlying the interactions between QUE and DNA are discussed. PMID- 22779796 TI - Structure-activity relationship for the reactivators of acetylcholinesterase inhibited by nerve agent VX. AB - Nerve agents such as sarin, VX and tabun are organophosphorus compounds able to inhibit an enzyme acetylcholinesterase (AChE). AChE reactivators and anticholinergics are generally used as antidotes in the case of intoxication with these agents. None from the known AChE reactivators is able to reactivate AChE inhibited by all kinds of nerve agents. In this work, reactivation potency of seventeen structurally different AChE reactivators was tested in vitro and subsequently, relationship between their chemical structure and biological activity was outlined. VX was chosen as appropriate member of the nerve agent family. PMID- 22779798 TI - QSAR study on 5-lipoxygenase inhibitors based on support vector machine. AB - QSAR study on a data set of 5-lipoxygenase inhibitors (1-phenyl [2H]-tetrahydro triazine-3-one analogues) was carried out by using Support Vector Regression (SVR) and physicochemical parameters. Wrapper methods were used to select descriptors, while Leave-One-Out Cross Validation (LOOCV) method and independent set test were used to judge the predictive power of different models. We found out that the generalization ability of SVR model outperformed multiple linear regression (MLR) and Partial Least Squares (PLS) models in this work. An online web server for activity prediction is available at http://chemdata.shu.edu.cn/qsar5lip. PMID- 22779799 TI - 3D-QSAR and docking studies on a series of benzothiadiazine derivatives as genotype 1 HCV polymerase inhibitors. AB - The Benzothiadiazine derivatives have been regarded as a novel class of HCV genotype 1 polymerase inhibitors. To explore the relationship between the structures of substituted Benzothiadiazine derivatives and their inhibitory activities against HCV, 3D-QSAR and molecular docking studies were performed on a dataset of ninty-eight compounds. The 3D-QSAR models resulted from seventy-eight molecules in the training set gave q(2) value of 0.81 and a test set of twenty compounds, gave predictive r(2) value of 0.94. 3D-QSAR model generated from kNN MFA along with the docking binding structures provided enough information about the structural requirements for better activity. The results can serve as a useful guideline to design novel HCV genotype 1 inhibitors with better potencies. PMID- 22779800 TI - 3D QSAR pharmacophore modeling for c-Met kinase inhibitors. AB - The receptor tyrosine kinase c-Met has multiple roles during cancer development and is currently considered as a promising target for cancer therapies. Pharmacophore models of c-Met kinase inhibitors have been developed based on 22 diverse compounds by using HypoGen algorithm implemented in Discovery studio program package. The best quantitative pharmacophore model, Hypo 1, which had the highest correlation coefficient (0.9623), consists of two hydrogen bond acceptors, one hydrophobic feature and two excluded volumes. Then best model was validated by test set prediction, Fischer randomization and decoy set. Besides, the features of Hypo1 were verified to correctly reflect the interactions between kinase active site and its ligands by comparison and superimposition of Hypo 1 in active site of c-Met kinase. The results shows that Hypo 1 has strong capability to identify c-Met kinase inhibitors and to predict the activities of structurally diverse molecules. Therefore, our pharmacophore models were considered as valuable tools for the discovery and development of specific c-Met kinase inhibitors. PMID- 22779801 TI - Synthesis, SAR and biological evaluation of natural and non-natural hydroxylated and prenylated xanthones as antitumor agents. AB - In order to explore the detailed structure-activity relationship (SAR) around xanthone scaffold bearing hydroxyl and prenyl moieties, twenty-nine natural and non-natural hydroxylated and prenylated xanthones have been synthesized and evaluated for their in vitro anti-proliferative activities against five human cancer cell lines, including HepG2 (hepatocelluar carcinoma), HCT-116 (colon carcinoma), A549 (lung carcinoma), BGC823 (gastric carcinoma) and MDAMB- 231 (breast carcinoma). The SAR analysis revealed that the anti-proliferative activity of the xanthones is substantially influenced by the position and number of attached hydroxyl and prenyl groups, and the presence of hydroxyl group ortho to the carbonyl function of xanthone scaffold contributes significantly to their cytotoxicity. The new prenylated xanthone 20 with a relatively simple structure, namely 1,3,8-trihydroxy-2-prenylxanthone, was found to exhibit potent antitumor activities comparable to alpha-mangostin against all the five cancer cell lines. Further mechanistic studies suggested that compound 20 induces apoptosis and causes cell cycle arrest at S phase in HepG2 cells. These results have highlighted compound 20 as a new potential lead candidate for future development of novel potent broad-spectrum antitumor agents. PMID- 22779802 TI - Synthesis and biological evaluation of novel pentacyclic triterpene derivatives as potential PPARgamma agonists. AB - Synthesis and biological evaluation of a novel series of substituted pentacyclic triterpene derivatives as potential PPARgamma agoinsts and glycogen phosphorylase inhibitors have been described. Compounds 11 and 17 showed potent PPARgamma agonistic activity and activated the transcription activity of PPARgamma in a dose-dependent manner. On the other hand, eleven compounds exhibited moderate inhibitory activity against rabbit muscle glycogen phosphorylase a (RMGPa), and triterpene 10 was the best one. Structure-activity relationship (SAR) is also discussed. PMID- 22779803 TI - Homology modeling and antagonist binding site study of the human histamine H2 receptor. AB - On the basis of the high resolution crystal structures of bovine rhodopsin, human beta2-adrenergic receptor and human A(2a) adenosine receptor, three-dimensional structure of the human histamine H2 receptor (HHR2) was developed by homology modeling. Results of the evaluations suggest that a high quality homology model for HHR2 has been obtained. Three antagonists, cimetidine, ranitidine and nizatidine, were applied to binding site study with this model through molecular docking, molecular dynamics simulations and the molecular mechanics-Poisson Boltzmann surface area calculations. One aspartic acid, Asp98 in transmembrane domain 7 (TM3), has been identified as major contributors to ligand binding by H bond interactions. Asn159 in TM4 and Asp186 in TM5 are of great importance in stabilizing HHR2- antagonist complexes. Two hydrophobic sites especially two residues, Val99 in TM3 and Phe254 in TM6, were identified to be essential for their strong hydrophobic interactions with antagonists. The findings reported here are in agreement with available experimental mutagenesis data. This study should be very helpful for a better understanding of the action mode of the antagonist and for guiding further drug design and mutagenesis studies. PMID- 22779804 TI - Synthesis of 2-(4-substitutedbenzylpiperazin-1-yl)-N-(2-oxo-2,3 dihydrobenzooxazol-6-yl)acetamides as inotropic agents. AB - We describe the synthesis and positive inotropic evaluation of a series of 2-(4 substitutedbenzylpiperazin-1-yl)-N-(2-oxo-2,3-dihydrobenzooxazol-6-yl)acetamides by measuring left atrial stroke volume in preparations of isolated rabbit hearts. Several compounds were developed from and showed favorable activities compared with the standard drug milrinone. Compound 4l was the most potent with an increased stroke volume of 11.78 +/- 0.18% (milrinone 6.36 +/- 0.13%) at 1 * 10( 4) M in our in-vitro study. The chronotropic effects of compounds having inotropic effects were also evaluated. PMID- 22779805 TI - Communication before coherence. AB - The hypothesis of communication through coherence proposes that coherent or synchronous oscillations in connected neural systems can promote communication. It has been applied mainly to how oscillations interact in connected networks. We tested by simulations whether information transmission about an external stimulus from one network to a second network is influenced by gamma oscillations, by whether the oscillations are coherent, and by their phase. Gamma oscillations were induced by increasing the relative conductance of AMPA to NMDA excitatory synapses. It was found that small associative connection strengths between the networks were sufficient to produce information transmission (measured by Shannon mutual information) such that the second attractor network took the correct decision based on the state of the first network. Although gamma oscillations were present in both networks, the synaptic connections sufficient for perfect information transmission about the stimulus presented to the network (100% correct, 1 bit of information) were insufficiently strong to produce coherence, or phase-locking, between the two networks; this only occurred when the synaptic strengths between the networks were increased by > 10 *. Further, the phase of the oscillations between the networks did not influence the information transmission or its speed at these connection strengths. Moreover, information transmission was as good when the AMPA-to-NMDA ratio was reduced to its normal value, and oscillations were not present. Similar results were found when the second network was not an attractor decision-making network. Thus information transmission can occur before synapses have been made sufficiently strong to produce coherence. PMID- 22779806 TI - High-resolution photocurrent mapping of carbon nanostructures. AB - The spatial resolution of photocurrent measurements on carbon nanostructures has reached 20 nm, as demonstrated by Hartschuh and co-workers for individual carbon nanotubes in this issue of ACS Nano. In this Perspective, we provide a brief overview of the applications of scanning photocurrent microscopy to various one- and two-dimensional nanostructures and highlight the importance of the optical antenna concept for future studies of the optoelectronic properties of hybrid nanostructures. PMID- 22779807 TI - Iron-catalyzed, highly regioselective synthesis of alpha-aryl carboxylic acids from styrene derivatives and CO2. AB - The iron-catalyzed hydrocarboxylation of aryl alkenes has been developed using a highly active bench-stable iron(II) precatalyst to give alpha-aryl carboxylic acids in excellent yields and with near-perfect regioselectivity. Using just 1 mol % FeCl(2), bis(imino)pyridine 6 (1 mol %), CO(2) (atmospheric pressure), and a hydride source (EtMgBr, 1.2 equiv), a range of sterically and electronically differentiated aryl alkenes were transformed to the corresponding alpha-aryl carboxylic acids (up to 96% isolated yield). The catalyst was found to be equally active with a loading of 0.1 mol %. Preliminary mechanistic investigations show that an iron-catalyzed hydrometalation is followed by transmetalation and reaction with the electrophile (CO(2)). PMID- 22779808 TI - On the influence of surfactants on the adsorption of polysaccharide-based polymers on cotton studied by means of fluorescence spectroscopy. AB - In this study, we examined the influence of surfactants on the adsorption of polymers on cotton fibers. The extent of polymer adsorption on cotton was determined directly by means of fluorescence spectroscopy using fluorescently labeled polymers. The investigation of polymer adsorption in the presence of different types of surfactants and for a large range of differently structured polymers allows us to obtain a rather general picture of this important issue. Systematic relationships between the presence of surfactant and the type of polymer can be deduced but cannot be cast in simple terms such as electrostatic interaction but instead depend on the detailed interaction between the surfactant and polymer both in solution and adsorbed on the cotton surface. A particularly complex situation arises for the case of oppositely charged surfactant and polymer because of the possibility of precipitate formation. The study of such complex systems not only is of scientific interest but also is of great commercial interest because both polymers and surfactants are parts of detergent formulations and cotton is one of the most abundantly used materials for fabrics. PMID- 22779906 TI - Post-traumatic head injury pituitary dysfunction. AB - Partial or complete pituitary dysfunction affects 33-50% of all traumatic brain injury (TBI) survivors and is a significant contributor to the overall disability burden. The hypophyseal vessels are anatomically vulnerable to shearing injuries, raised intracranial pressure and anterior base of skull fractures, and pituitary ischaemia or haemorrhage is a common finding at autopsy. Post-traumatic hypopituitarism (PTHP) can affect all grades of severity of injury and is often difficult to diagnose, as its features largely overlap with common post concussive symptoms. PTHP has a wide range of manifestations, including fatigue, myopathy, cognitive difficulties, depression, behavioural changes or life threatening complications such as sodium dysregulation and adrenal crisis. In some instances, mild PTHP can recover, at least partially, but cases of late onset are also known. At present, there is no consensus on whether all TBI patients should be screened (including mild TBI) and at what time points, given that neuroendocrine tests in the acute phase are simply likely to reflect a non specific trauma response rather than true pituitary damage and that the time course of PTHP is unclear. A full investigation of the hypothalamic-pituitary axis requires specialized neuroendocrine assessment, including stimulation tests, as random hormone levels can be misleading in this context. Given the high incidence of TBI, this may have significant resource implications for Endocrinology services but, on the other hand, patients with PTHP may receive suboptimal rehabilitation unless the underlying hormone deficiency is identified and treated. PMID- 22779907 TI - Antimicrobial-associated diarrhoea in three equine referral practices. AB - REASONS FOR PERFORMING STUDY: Although antimicrobial-associated diarrhoea (AAD) is the most frequently observed adverse effect of antimicrobial therapy in horses, few multicentred studies on the prevalence of AAD have been performed. OBJECTIVES: To determine the prevalence of AAD in horses that developed diarrhoea after antimicrobial treatment for nondiarrhoeic conditions and identify the antimicrobials used. METHODS: The 2009 database of 3 referral hospitals was searched to identify nonhospitalised horses (weanling age or older) treated with antimicrobials for nongastrointestinal conditions. Horses with these criteria that presented with diarrhoea during 2009 were included in the study. Additional information, including antimicrobial administered and results of faecal pathogen testing, was gathered on each hospitalised case. RESULTS: Of the 5251 horses treated with antimicrobials for nongastrointestinal signs, 32 were diagnosed with probable AAD, a prevalence of 0.6% (95% confidence interval: 0.43-0.86%). The AAD diagnosed horses had an 18.8% (6/32) mortality rate. Horses with AAD had been treated for an average of 4.2 days. The most frequently used antimicrobials in horses with AAD were gentamicin in combination with penicillin (n = 7), enrofloxacin (n = 7) and doxycycline (n = 4). Clostridium difficile was identified in faecal samples from 4 horses, 2 of which died and Salmonella from 3 horses. CONCLUSIONS: Results indicated that the prevalence of AAD is low. Any antimicrobial class commonly used in equine practice is a potential cause of equine AAD. Other risk factors, such as opportunistic enteropathogens, may play a part in the development of diarrhoea secondary to antimicrobial usage. POTENTIAL RELEVANCE: Although the risk of equine AAD is low, this sequela of antimicrobial treatment is possible especially when opportunistic enteropathogens or other risk factors are present. Because drugs from any antimicrobial class can be potentially involved in AAD, clinicians have additional incentive to ensure the judicious use of antimicrobial agents. PMID- 22779908 TI - Calorimetric and theoretical study of the interaction between some saccharides and sodium halide in water. AB - Dilution enthalpies and mixing enthalpies of sodium halide and some saccharides (glucose, galactose, xylose, arabinose, fructose, and sucrose) in aqueous solution were determined by calorimetric measurements at 298.15 K. The values were used to determine enthalpic pair interaction parameters. Combined with Gibbs energy pair parameters, entropic pair interaction parameters were also obtained. Theoretical calculations at the B3LYP/6-311++G(d,p) level were carried out to provide the information of structures and thermodynamic functions. The information reveals the thermodynamic essence of the interactions between sodium halide and saccharides in aqueous solutions. The experimental results and theoretical calculations show that the sign of enthalpic pair interaction parameter 2upsilonh(ES) is determined by the direct interaction between saccharides and ions, whereas the difference in value of 2upsilonh(ES) for different saccharides or electrolytes depends on the partial dehydration of saccharides or anions in aqueous solution. The difference in value of entropic pair interaction parameters depends partly on the different dominant interactions in the process of partial dehydration of saccharides or ions. An enthalpy-entropy compensation relationship was observed for the sodium bromide-aldopyranose-water systems. Remarkably, it can be conjectured that the hydration entropy of glucose is lower than for other monosaccharides. Perhaps it is one of the reasons why glucose plays an important role in living organisms rather than other monosaccharides. PMID- 22779909 TI - Novel mouth-exercising device for oral submucous fibrosis. AB - Oral submucous fibrosis (OSMF) is a chronic inflammatory disease resulting in progressive juxtaepithelial fibrosis of the oral soft tissues and can cause increasing difficulty in mastication, swallowing, speaking, and mouth opening. The treatment of severe trismus requires a combination of surgical release and physiotherapy. Often physiotherapy alone can modify tissue remodeling in OSMF to increase oral opening. This article describes the fabrication and use of a new mouth-exercising device that helps the patient to squeeze/stretch the cheek mucosa to increase elasticity. The device can be used as a sole treatment modality or can be used in association with pharmacological and surgical treatment modalities for OSMF. Improvement in mouth opening was observed in four OSMF patients treated with a mouth-exercising device for 6 months as a sole treatment modality. PMID- 22779910 TI - Combinations of classical time-honoured topicals in plaque psoriasis: a systematic review. AB - BACKGROUND: Despite the availability of newer topical treatments, classical topical treatments for chronic plaque psoriasis still have an important position for selected patient populations. The vast majority of patients are treated with a combination of topicals. The question arises: what is the evidence behind these approaches? OBJECTIVES: To systematically review all available literature on efficacy and safety of combinations of classical topical treatments in chronic plaque psoriasis, including all combinations with dithranol, coal tar and penetration enhancers, and ultimately, to propose recommendations for combination treatment. METHODS: Standardized literature searches in PubMed, EMBASE and the Cochrane Controlled Clinical Trial Register, and allocation of the degree of evidence was carried out. RESULTS: In total 2918 publications on topical combination therapy were revealed, of which 48 articles on combinations of classical treatments. In this article, the results concerning the 19 included publications are stated. The majority of combination regimens is at least as effective as monotherapies, and is generally well tolerated. CONCLUSIONS: Methods of classical treatments are not standardized and different protocols in different treatment settings are used. Therefore the interpretation of study results cannot be generalized. Most evidence was found to recommend the use of a combination regimen of topical corticosteroids and salicylic acid, above monotherapy with either component. Also, the combinations of dithranol with superpotent corticosteroids or with coal tar may be preferred above both monotherapies. In case first-line treatments and systemic therapies are not effective or contraindicated, combinations of classical topicals may provide an important opportunity. PMID- 22779911 TI - Missed epidemics and missing links: international birth cohort trends in multiple sclerosis. AB - BACKGROUND AND PURPOSE: Many hypotheses on the etiopathogenesis of multiple sclerosis (MS) focus on risk factors occurring early in life. This study examined the variability of birth cohort trends in international MS data by means of age period-cohort (APC) analysis. METHODS: The data from 25 countries were taken from the WHO mortality database. Data were encoded according to the International Classification of Diseases and covered slightly varying periods between 1951 and 2009. The APC analyses were based on logit models applied to cohort tables with 5 year age- and period intervals. RESULTS: In most countries, the birth cohort estimates peaked in those born in the first half of the 20th century. In countries from Central and Western Europe, the peak concerned those born before and around 1920. A second group of countries (Denmark, Sweden, Italy, Ireland, Scotland) shared a later peak amongst cohorts born in the 1920s and 1930s. Group 3 included Commonwealth countries, the USA and Norway, with a double or extended peak starting in the 1910s or 1920s, and ending by the 1950s. The fourth group, consisting of Mediterranean countries and Finland, was characterized by a steady increase in the birth cohort estimates until the 1950s. The fifth group with countries from Eastern Europe and Japan showed no particular pattern. CONCLUSIONS: Birth cohort trends have influenced the change in MS risk across the 20th century in many Western countries. This silent epidemic points to a most important but unknown latent risk factor in MS. PMID- 22779912 TI - Taurine in milk and yoghurt marketed in Italy. AB - Taurine, a free amino acid, was studied as natural compound of different typologies of milk: pasteurized, ultra-high temperature (UHT), microfiltered whole and semi-skimmed cow's milk; pasteurized and UHT goat's whole milk and raw buffalo's whole milk. Moreover, taurine contents in yoghurt from cow and goat's milk were evaluated. The data obtained in this research showed that no significant variations of taurine occurred in cow's milk subjected to different technological processes and between whole and semi-skimmed milk. The amount of taurine was less (p < 0.05) in cow's milk (0.60 mg/100 g) than in goat and buffalo's milk (6.55 and 7.32 mg/100 g, respectively). No significant differences in taurine occurred between goat and buffalo's samples. The amounts of taurine in yoghurt reflected, substantially, the content of this molecule in the milk of the relevant animal species. These results are noteworthy because data available in the literature on this molecule in commercial dairy products are old or few. PMID- 22779913 TI - Increased salivary chromogranin A in women with severe negative mood states in the premenstrual phase. AB - The present study investigated whether salivary chromogranin A (CgA), a psychological stress marker associated with sympathetic nervous system activity, changes during the menstrual cycle in women with different degrees of premenstrual psychoemotional symptoms. Forty-five women (28.6 +/- 1.3 years) with regular menstrual cycles participated in this study. Salivary CgA and cortisol were measured during the follicular and late-luteal phases. The authors used the Profile of Mood State (POMS) to assess current mood states of subjects in each menstrual phase and divided the subjects into three groups depending on increase of total mood disturbance (TMD), a global measure of affective states of POMS from the follicular to the late-luteal phase: Low (4.1 +/- 0.7%), Middle (18.7 +/ 1.2%) and High (51.7 +/- 7.4%). Results showed no intramenstrual cycle differences in salivary CgA in the Low and Middle groups. Women in the High group, in contrast, had a significantly higher level of salivary CgA in the late luteal phase compared to that of the follicular phase. Additionally, salivary CgA level significantly and positively correlated with TMD and four emotional subscales: tension-anxiety, depression-dejection, anger-hostility and confusion in the late-luteal phase. No intergroup or menstrual-cycle difference occurred in the salivary cortisol. This study indicates a significant late-luteal increase in salivary CgA, reflecting an increase of sympathetic nerve activity in women who experience a substantial increase (>30%) in a cluster of negative psychoemotional symptoms premenstrually. Furthermore, salivary CgA, as opposed to salivary cortisol, could serve as a reliable noninvasive biomarker to more sensitively evaluate neuropsychophysiological fluctuations during the menstrual cycle. PMID- 22779914 TI - Biophysical and structural studies of the human calcium- and integrin-binding protein family: understanding their functional similarities and differences. AB - The human calcium- and integrin-binding protein 1 (CIB1) plays important roles in various cellular functions. In this study, three other members of this protein family (CIB2-4: CIB2, CIB3, and CIB4) were purified and subsequently characterized using biophysical and structural approaches. As expected from sequence alignments, CIB2-4 were shown to bind calcium (Ca(2+)) and magnesium (Mg(2+)) ions. Binding of Ca(2+) or Mg(2+) ions changes the secondary structure of CIB2-4 and the exposure of hydrophobic surface area. Ca(2+) and Mg(2+) ions also stabilize the tertiary structures for CIB2 and CIB3. Through in vitro binding experiments, we show that CIB2 can interact with the integrin alphaIIb cytoplasmic domain and the integrin alpha7b membrane-proximal fragment. Fluorescence experiments using a 7-azatryptophan labeled peptide demonstrate that CIB2, CIB3, and CIB4 are binding partners for the integrin alphaIIb subunit, which suggests that they are potentially involved in regulating integrin alphaIIb subunit activation. The distinct responses of alphaIIb to the different CIB3 and CIB4 metal (Ca(2+) and Mg(2+)) binding states imply a potential connection between the calcium and integrin signaling pathways. PMID- 22779915 TI - Phenguignardic acid and guignardic acid, phytotoxic secondary metabolites from Guignardia bidwellii. AB - Bioactivity-guided isolation led to the identification of phenguignardic acid (2), a new phytotoxic secondary metabolite from submerged cultures of grape black rot fungus, Guignardia bidwellii. The compound is structurally related to guignardic acid (1), a dioxolanone moiety-containing metabolite isolated previously from Guignardia species. However, in contrast to guignardic acid, which is presumably synthesized from deamination products of valine and phenylalanine, the biochemical precursor for the biosynthesis of the new phytotoxin appears to be exclusively phenylalanine. Guignardic acid was also found in extracts of cultures from Guignardia bidwellii. The phytotoxic activities of both compounds were assessed in plant assays using either detached vine leaves or intact plants. Antimicrobial and cytotoxic activities of phenguignardic acid were determined. PMID- 22779916 TI - Reversible chiral switching of bis(phthalocyaninato) terbium(III) on a metal surface. AB - We demonstrate a reversible chiral switching of bis(phthalocyaninato) terbium(III) molecules on an Ir(111) surface by low temperature scanning tunneling microscopy. With an azimuthal rotation of its upper phthalocyanine ligand, the molecule can be switched between a chiral and an achiral configuration actuated by respective inelastic electron tunneling and local current heating. Moreover, the molecular chiral configuration can be interchanged between left and right handedness during the switching manipulations, thereby opening up potential nanotechnological applications. PMID- 22779917 TI - Negative middle ear pressure and otitis media with effusion after surgery under general anesthesia. AB - CONCLUSION: Negative middle ear pressure was observed in many patients and otitis media with effusion (OME) developed in 3.3% of ears after surgery under general anesthesia. Gas dynamics in the middle ear cavity induced by nitrous oxide inhalation anesthesia and transient blockage of the eustachian tube induced by surgery are considered to be involved in development of OME after surgery under general anesthesia. OBJECTIVES: The goal of this prospective study was to investigate middle ear pressure and the prevalence of middle ear effusion in patients after surgery under general anesthesia, to ascertain whether surgery under general anesthesia induces OME. METHODS: Otoscopic inspection and tympanometry were performed before surgery (Pre), 1-2 days after surgery (Post 1), and 5-9 days after surgery (Post-2) under general anesthesia in 180 ears of 97 adult patients. RESULTS: Effusion accumulated in the tympanum in six ears (3.3%) of five patients at Post-1. All patients were anesthetized with nitrous oxide. At Post-2, effusion disappeared in all cases. The mean middle ear pressure in all ears was -17.8 daPa at Pre and -60.6 daPa at Post-1, showing a significant reduction from Pre to Post-1 (p < 0.001). At Post-2, the pressure was -18.4 daPa, with no significant difference from that at Pre (p = 0.74). PMID- 22779918 TI - Factors influencing tissue nitrate concentration in field-grown wild rocket (Diplotaxis tenuifolia) in southern England. AB - Wild rocket (Diplotaxis tenuifolia) is a leafy vegetable known for its high tissue nitrate concentration (TNC) which can exceed the limits set in the relevant European legislation designed to protect human health. The aim of this work was to understand the factors influencing TNC and to develop best practice guidelines to growers. Commercial crops of field-grown wild rocket were studied over two seasons. In 2010, ten separate crops were sampled representing a range of soil types and time periods during the summer. Two fields sampled using a 'W'- or 'X'-shaped sampling pattern demonstrated that 10 incremental samples bulked to make 1 kg of fresh material could be used to provide an adequate sample for determination of TNC in the wild rocket crop, as is the case for other leafy vegetables. Of eight commercial crops sampled in 2010 with an average nitrogen (N) fertiliser application of 104 kg N ha(-1), two exceeded the limit of 6000 mg NO3(-) kg(-1) set in the legislation. In 2011, six N response experiments were carried out, and only two sites showed a significant yield response to N fertiliser. The reason for the lack of response at the other sites was principally due to high levels of soil mineral N prior to drilling, meaning the crops' requirement for N was satisfied without additional fertiliser N. In the experimental situation at an N fertiliser application rate of 120 kg N ha(-1), 50% of crops would have exceeded the 6000 mg NO3(-) kg(-1) limit. In both seasons, low radiation levels in the 5 days prior to harvest were shown to increase TNC, although the relationship was also influenced by N supply. Strategies for optimising N nutrition of field-grown wild rocket are discussed. PMID- 22779919 TI - Isomerization between 2-(2,4-dihydroxystyryl)-1-benzopyrylium and 7-hydroxy-2-(4 hydroxystyryl)-1-benzopyrylium. AB - 2-Phenyl-1-benzopyrylium (flavylium) and 2-styryl-1-benzopyrylium (styrylflavylium) cations establish in aqueous solution a series of equilibria defining chemical reaction networks responsive to several stimuli (pH, light, redox potential). Control over the mole fraction distribution of species by applying the appropiate stimuli defines a horizontal approach to supramolecular chemistry, in agreement with the customary bottom-up approach toward complex systems. In this work, we designed an asymmetric styrylchalcone able to cyclize in two different ways, producing two isomeric styrylflavylium cations whose chemical reaction networks are thus interconnected. The chemical reaction networks of 2-(2,4-dihydroxystyryl)-1-benzopyrylium (AH(+)) and 7-hydroxy-2-(4 hydroxystyryl)-1-benzopyrylium (AH(+)(iso)) comprise the usual species observed in flavylium-derived networks, in this case, the styryl derivatives of quinoidal bases, hemiketals, and chalcones. The thermodynamics and kinetics of the crossed networks were characterized by the use of UV-vis absorption and NMR spectroscopy as well as time-resolved pH jumps followed by stopped-flow. The two styrylflavylium cations are connected (isomerize) through two alternative intermediates, the asymmetric trans-styrylchalcone (Ct) and a spiropyran-type intermediate (SP). At pH = 1, AH(+) slowly evolves (k(obs) ~ 10(-5) s(-1)) to a mixture containing 62% AH(+)(iso) through the Ct intermediate, while at pH = 5, the SP intermediate is involved. The observed rate constants for the conversion of the styrylflavylim cations into equilibrium mixtures containing essentially Ct follow a pH-dependent bell-shaped curve in both networks. While at pH = 1 in the dark, AH(+) evolves to an equilibrium mixture containing predominantly AH(+)(iso), irradiation at lambda > 435 nm induces the opposite conversion. PMID- 22779920 TI - Low glycemic index treatment for seizures in Angelman syndrome. AB - PURPOSE: The low glycemic index treatment (LGIT) is a high fat, limited carbohydrate diet used in the treatment of epilepsy. The purpose of this study was to assess the efficacy and tolerability of the LGIT for the treatment of refractory seizures in pediatric patients with Angelman syndrome. METHODS: A pediatric Angelman syndrome cohort with refractory epilepsy was treated with the LGIT and followed prospectively over 4 months. Parents recorded a daily seizure log for a minimum of 1 month prior to the start of treatment as well as throughout the LGIT trial. Electroencephalography (EEG) and neuropsychological assessments (Scales of Independent Behavior-Revised and the Vineland Adaptive Behavior Scales-2nd Edition were obtained for each subject at both baseline and 4 month follow-up time points. Clinical evaluations of subjects were completed by a neurologist and dietitian at the time of enrollment, as well as following both the first and fourth months of dietary therapy. At each time point, blood for laboratory chemistries was drawn and anthropometric measures were obtained. KEY FINDINGS: Six children (mean age 3.3 years, range 1.1-4.8) with genetically confirmed Angelman syndrome initiated the LGIT, and completed the trial with no significant adverse events. Cohort averages for indices of seizure severity were as follows: age of 1.6 years at seizure onset, 3 lifetime antiepileptic drugs tried (range 1-6), and baseline seizure frequency of 10.1 events/week (range: 0.4 30.9). All subjects had a decrease in seizure frequency on the LGIT, with five of six exhibiting >80% seizure frequency reduction. All posttrial EEG studies showed improvement and three of four children with epileptiform activity on his or her baseline EEG had no discharges present on follow-up EEG. Developmental gains were noted by parents in all cases, although few of these neurocognitive gains were statistically significant on neuropsychological assessment. SIGNIFICANCE: This is the first prospective study assessing the LGIT for epilepsy. Our results indicate that this dietary therapy is highly effective in treating Angelman syndrome related seizures. The diet was well tolerated by subjects as evidenced by five of six subjects remaining on the LGIT after completion of the trial. Beyond the prospective trial window, all five subjects who remained on the diet had >90% seizure reduction after 1 year of LGIT therapy. Despite the small sample size in this prospective study, the results indicate a potentially higher degree of efficacy of the LGIT for the Angelman syndrome population than that observed in the general epilepsy population. Although this study is too small to make definitive recommendations, these results suggest that the LGIT is a promising treatment option for Angelman syndrome-related epilepsy. PMID- 22779921 TI - A yeast two-hybrid screen reveals that osteopontin associates with MAP1A and MAP1B in addition to other proteins linked to microtubule stability, apoptosis and protein degradation in the human brain. AB - Osteopontin (OPN) expression is reduced in surviving dopaminergic neurones in the substantia nigra (SN) in Parkinson's disease (PD), and protects against MPP(+) induced cell death in primary mesencephalic cultures and 6-OHDA-induced cell loss in the rat, while inactivation of OPN aggravates cell death. OPN is thought to act through interactions with integrin receptors or CD44. However, the specific protein interactions involved in OPN-mediated neuroprotection are unknown and are the focus of this study. The yeast two-hybrid (YTH) technique was utilised to investigate OPN-protein interactions, using full-length human OPN to screen a human foetal brain cDNA library. Proteins involved in apoptosis, protein degradation and microtubule stability were identified as OPN binding partners. These included: MAP1A and MAP1B, which regulate microtubule stability; RNF138, an E3 ubiquitin-ligase; proteasome beta1 subunit, a subunit of the 20S proteasome involved in the ubiquitin-dependent cleavage of peptides; BAG6, SGTAlpha and EF1A, proteins implicated in control of apoptosis; DnaJB1, a co-chaperone of Hsp70s; and pleiotrophin, a growth factor. The use of site-directed mutagenesis to modify known OPN protein binding sites outside the RGD integrin binding domain, specifically Y165A and D139E, inhibited some of these interactions. Further investigation using affinity pull-down assays, co-immunoprecipitation and immunohistochemistry confirmed that OPN associates with MAP1A and MAP1B in rat SN and striatum. These findings indicate a role for OPN in the regulation of microtubule dynamics, apoptosis and proteolysis in the brain, suggesting that OPN may act as an endogenous multifunctional protective protein in PD. PMID- 22779922 TI - Comparing graphene-TiO2 nanowire and graphene-TiO2 nanoparticle composite photocatalysts. AB - We demonstrate that uniform dispersion of TiO(2) on graphene is critical for the photocatalytic effect of the composite. The hydrothermal method was employed to synthesize TiO(2) nanowires (NW) and then fabricate graphene-TiO(2) nanowire nanocomposite (GNW). Graphene oxide (GO) reduction to graphene and hybridization between TiO(2) NWs and graphene by forming chemical bonding was achieved in a one step hydrothermal process. Graphene-TiO(2) nanoparticle (NP) nanocomposite (GNP) was also synthesized. Photocatalytic performance and related properties of NP, NW, GNP, and GNW were comparatively studied. It was found that by incorporation of graphene, GNP and GNW have higher performance than their counterparts. More importantly, it was found that NWs, in comparison with NPs, have more uniform dispersion on graphene with less agglomeration, resulting in more direct contact between TiO(2) and graphene, and hence further improved electron-hole pairs (EHPs) separation and transportation. The adsorbability of GNW is also found to be higher than GNP. The result reveals that the relative photocatalytic activity of GNW is much higher than GNP and pure NWs or NPs. PMID- 22779923 TI - Friction and adhesion of gecko-inspired PDMS flaps on rough surfaces. AB - Geckos have developed a unique hierarchical structure to maintain climbing ability on surfaces with different roughness, one of the extremely important parameters that affect the friction and adhesion forces between two surfaces. Although much attention has been paid on fabricating various structures that mimic the hierarchical structure of a gecko foot, yet no systematic effort, in experiment or theory, has been made to quantify the effect of surface roughness on the performance of the fabricated structures that mimic the hierarchical structure of geckos. Using a modified surface forces apparatus (SFA), we measured the adhesion and friction forces between microfabricated tilted PDMS flaps and optically smooth SiO(2) and rough SiO(2) surfaces created by plasma etching. Anisotropic adhesion and friction forces were measured when sliding the top glass surface along (+y) and against (-y) the tilted direction of the flaps. Increasing the surface roughness first increased the adhesion and friction forces measured between the flaps and the rough surface due to topological matching of the two surfaces but then led to a rapid decrease in both of these forces. Our results demonstrate that the surface roughness significantly affects the performance of gecko mimetic adhesives and that different surface textures can either increase or decrease the adhesion and friction forces of the fabricated adhesives. PMID- 22779924 TI - Novel creatine biosensors based on all solid-state contact ammonium-selective membrane electrodes. AB - Novel creatine bienzymatic potentiometric biosensors were prepared by immobilizing urease and creatinase on all solid-state contact PVC-containing palmitic acid and carboxylated PVC matrix membrane ammonium-selective electrodes without inner reference solution. Potentiometric characteristics of biosensors were examined in physiological model solutions at different creatine concentrations. The linear working range and long-term sensitivity of the biosensors were also determined. The creatine biosensors prepared by using the carboxylated PVC membrane electrodes showed more effective performance than those of the PVC containing palmitic acid membrane electrodes. Creatine assay in serum samples was successfully carried out by using the standard addition method. PMID- 22779925 TI - Variation in peak growing season net ecosystem production across the Canadian Arctic. AB - Tundra ecosystems store vast amounts of soil organic carbon, which may be sensitive to climatic change. Net ecosystem production, NEP, is the net exchange of carbon dioxide (CO(2)) between landscapes and the atmosphere, and represents the balance between CO(2) uptake by photosynthesis and release by decomposition and autotrophic respiration. Here we examine CO(2) exchange across seven sites in the Canadian low and high Arctic during the peak growing season (July) in summer 2008. All sites were net sinks for atmospheric CO(2) (NEP ranged from 5 to 67 g C m(-2)), with low Arctic sites being substantially larger CO(2) sinks. The spatial difference in NEP between low and high Arctic sites was determined more by CO(2) uptake via gross ecosystem production than by CO(2) release via ecosystem respiration. Maximum gross ecosystem production at the low Arctic sites (average 8.6 MUmol m(-2) s(-1)) was about 4 times larger than for high Arctic sites (average 2.4 MUmol m(-2) s(-1)). NEP decreased with increasing temperature at all low Arctic sites, driven largely by the ecosystem respiration response. No consistent temperature response was found for the high Arctic sites. The results of this study clearly indicate there are large differences in tundra CO(2) exchange between high and low Arctic environments and this difference should be a central consideration in studies of Arctic carbon balance and climate change. PMID- 22779926 TI - Lateralization of temporal lobe epilepsy using resting functional magnetic resonance imaging connectivity of hippocampal networks. AB - PURPOSE: Early surgical intervention can be advantageous in the treatment of refractory temporal lobe epilepsy (TLE). The success of TLE surgery relies on accurate lateralization of the seizure onset. The purpose of this study was to determine whether resting functional MRI (fMRI) connectivity mapping of the hippocampus has the potential to complement conventional presurgical evaluations in distinguishing left from right TLE. In addition, we sought to determine whether this same network might separate patients with favorable from unfavorable postoperative outcomes. METHODS: Resting fMRI acquisitions were performed on 21 patients with TLE and 15 healthy controls. The patients included seven patients with left TLE and seven patients with right TLE with seizure-free postoperative outcome, and five patients with left TLE and two patients with right TLE with recurring seizures after surgery. Functional connectivity maps to each hippocampus were determined for each subject and were compared between the controls and the seizure-free patients with left TLE and with right TLE. The one network identified was then quantified in the patients with TLE and recurring seizures. KEY FINDINGS: The resting functional connectivity between the right hippocampus and the ventral lateral nucleus of the right thalamus was the most statistically significant network to distinguish between seizure-free patients with left TLE and with right TLE with high sensitivity and specificity. This connectivity was also significantly greater in the seizure-free patients with left TLE than the healthy controls. Finally, six of the seven patients in whom seizures recurred after surgery had connectivity values in this network unlike those who were seizure-free. SIGNIFICANCE: This study identified a region in the ventral lateral nucleus of the right thalamus whose connectivity to the hippocampi separates left from right TLE subjects. This suggests that the quantification of resting-state functional magnetic resonance imaging (MRI) connectivity across this network may be a potential indicator of lateralization of TLE that may be added to other presurgical MRI assessments. Further validation in a larger, independent cohort is required. PMID- 22779927 TI - Variation of radiation-sensitivity of neural stem and progenitor cell populations within the developing mouse brain. AB - PURPOSE: We investigated the DNA damage response (DDR) of fetal neural stem and progenitor cells (NSPC), since exposure to ionizing radiation can severely impair the brain development. MATERIAL AND METHODS: We compared apoptosis induction in the dorsal telencephalon and the lateral ganglionic eminences (LGE) of mouse embryos after an in utero irradiation. We used two thymidine analogs, together with the physical position of nuclei within brain structures, to determine the fate of irradiated NSPC. RESULTS: NSPC did not activate an apparent protein 21(p21)- dependent G1/S checkpoint within the LGE as their counterparts within the dorsal telencephalon. However, the levels of radiation-induced apoptosis differed between the two telencephalic regions, due to the high radiation sensitivity of intermediate progenitors of the LGE. Besides radial glia cells, that function as neural stem cells, were more resistant and were reoriented toward self-renewing within hours following irradiation. CONCLUSIONS: The lack of the p21-dependent-cell cycle arrest at the G1/S transition appears to be a general feature of NSPC in the developing brain. However, we found variation of radiation-response in function of the types of NSPC. Factors involved in DDR and those involved in the regulation of neurogenesis are intricately linked in determining the cell fate after irradiations. PMID- 22779928 TI - Inhibition effects of mangosenone F from Garcinia mangostana on melanin formation in B16F10 cells. AB - Melanogenesis can be controlled by tyrosinase inhibition or by blocking the maturation processes of tyrosinase and its related proteins. Mangostenone F was isolated from the seedcases of Garcinia mangostana . Mangostenone F was shown to be inactive against tyrosinase (IC50 > 200 MUM) but was a potent alpha glucosidase inhibitor in vitro (IC50 = 21.0 MUM). Mangostenone F was found to inhibit production of melanin in the mouse melanoma cell line B16F10. Importantly, unlike most glycosidase inhibitors, mangostenone F displayed very low cytotoxicity (EC50 > 200 MUM). The Western blot for expression levels of proteins involved in melanogenesis showed that mangostenone F down-regulated tyrosinase and TRP-2 expression. Treating B16F10 cells with mangostenone F significantly increased the susceptibility of tyrosinase to endoglycosidase H digestion, indicating that tyrosinase was unable to mature fully and pass to the trans-golgi apparatus. Consistent with these data, in lysate assays, mangostenone F was shown to be a better inhibitor of alpha-glucosidases than deoxynojirimycin, a representative glycosidase inhibitor. PMID- 22779929 TI - Effects of lycopene on the model of oleic acid-induced acute lung injury. AB - INTRODUCTION: This study, we aimed to investigate the protective effect of lycopene in lung injury rat model. MATERIALS AND METHODS: Twenty eight Wistar rats were enrolled into the study. Control group (n= 7) were applied PBS + ethanol (9/1). A single dose of 100 mg/kg oleic acid (OA) intravenously was administrated to OA group (n= 7). One mL of corn oil was given daily to corn oil + OA group (n= 7) by gavage for five weeks. Lycopene was given by gavage to lycopene + OA group (n= 7) for five weeks. At the end of the 5th weeks, OA were given. Four hour after OA administration, lung tissue, blood samples were taken. Malondialdehyde, superoxide dismutase, glutathione-peroxidase, catalase levels were determined. RESULTS: Malondialdehyde levels of serum, lung tissues were increased in OA, corn oil + OA groups than control, where as decreased to controls levels in lycopene + OA group (p< 0.05). Superoxide dismutase, glutathione-peroxidase activities of serum, tissue increased moderetaly or they were closed with control values. There was significant increase in lycopene + OA group values. Histopathological examination of control group was normal. OA, cornoil + OA groups had perivascular, alveolar edema, hemorrage, prominent neutrophil infiltration, destruction in alveolar structure. Lycopene + OA group had less neutrophilic infiltration, perivascular, alveolar edema. CONCLUSION: Lycopene rich diet may have an important role preventing damages in lungs. PMID- 22779930 TI - Study of the prevalence of sleep apnea syndrome's symptoms in a Moroccan population. AB - INTRODUCTION: Sleep apnea syndrome is increasingly common in the general population and is under-diagnosed but we lack studies on the estimation of its specific prevalence in several populations including Morocco. MATERIALS AND METHODS: The aim of the study is to determine the prevalence of the main clinical symptoms of sleep apnea syndrome including snoring, witnessed apnea and excessive daytime sleepiness in a middle aged Moroccan population through an epidemiological investigation in 288 men and 215 women, aged between 21 to 66 years who completed two self-questionnaires: the Berlin questionnaire to assess sleep and the Epworth scale to assess daytime sleepiness. RESULTS: The mean age was 42.7 years +/- 14.3. The Epworth Sleepiness Scale was on average 6.9 +/- 3.4 (range: 1-16). It was above 10 in 21.7% in favor of excessive daytime sleepiness. The prevalence of snoring and apnea was respectively 54.7% and 11.1% in the general population, 63.9% and 13.9% in men, 42.3% and 7.4% in women. Forty eight subjects (9.5%) including 13 women and 35 men had the combination of these three main clinical signs suggestive of sleep apnea syndrome. This subpopulation was older (p= 0.04) and with more overweight (p= 0.03) than the general population. Hypertension rate was not statistically higher in this subgroup. CONCLUSION: Prevalence of the main symptoms of sleep apnea syndrome is high in our study (9.5%). Polygraphy or polysomnography is warranted to diagnose and have an exact prevalence in the Moroccan population. PMID- 22779931 TI - [Mortality and factors affecting mortality in chronic obstructive pulmonary disease]. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is one of the major causes of mortality and morbidity in the world. Mortality rates vary between 15 54% in investigations. There is a limited number of studies evaluating factors associated with mortality and morbidity in our country. The aim of this study is to detect the mortality rate and to investigate the factors affecting mortality. PATIENTS AND METHODS: 427 patients with COPD between July 2004-November 2005 were evaluated. RESULTS: Mortality rate was found to be 17.3% at the end of four years. Deaths were most frequently due to pulmonary causes and secondly cardiac factors. Deaths due to lung cancer were 31%. Age, amount of smoking, COPD stage, FEV1 (L), FEV1% predicted, FVC (L), FVC% predicted, FEV1/FVC, PEF (L/sn), PEF% predicted, FEF25-75 (L) and FEF25-75% predicted values, presence of comorbid diseases, Modified Borg Scale and dyspnea severity according to MMRC, six minutes walking test and oxygen saturation following the test, BODE index, SF-36 quality of life questionnaire, physical function, physical role, emotional role and energy scores parameters and all parameters of SGRQ questionnaire were found to be significantly associated with mortality. CONCLUSION: COPD is a disease with high mortality and is one of the problems related with the public health. In the follow up of COPD, the usage of other measures like exercise capacity and quality of life besides spirometric measures should be encouraged. To make the patients and cases in the risky group conscious of their disease is important since the risk factors are preventable. This method may also contribute to the prevention of comorbid diseases. PMID- 22779933 TI - [Factors that increasing tendency to smoking cessation]. AB - INTRODUCTION: Cigarette smoking is just important problem of public health. In the present study, our aim; was to determine to factors that increasing tendency to smoking cessation, the cases who are involved to policlinic of smoking cessation. MATERIALS AND METHODS: Two hundred-forty five cigarette smokers were included in this study. It was recorded demographic signs, the novel of cigarette smoking, the degree of knowledge about the harmful of smoking in their opinion, the reason of starting to cigarette. It was evaluated that the principle reason to come to policlinic of smoking cessation and the other reasons. RESULTS: There were 53.9% male, 46.1% female in our study. Median (min-max) age was 45 (21-73) in females, 42 (20-75) in males. When evaluating the state of education; there was 35.9% primary school, 31.4% high school, 7.3% academy, 25.3% university graduates. 97.1% in all participants have used only cigarette smoking from tobacco products. Primarily reasons were 44% the fear of deterioration of health, 16.3% to be better model for their children, 9.8% to have disease at the time and 6.9% breathlessness for smoking cessation. Secondary reasons were of smoking harm to the environment, economic reasons, bad smell, being a good example of the environment and recommended by a physician. CONCLUSION: The most of cases are want to quit smoking because of smoking harm to their health. Specially, parents wish to quit smoking because of they don't want to be bad model for their children. As a result; it is given to necessary support to participants who are this awareness in policlinics of smoking cessation. However, we think that it was necessity that should be continue increase of the therapy to growing to these awareness for the smokers who couldn't be enough awareness and who didn't think of quit smoking. PMID- 22779932 TI - [A pharmacovigilance study in chest diseases outpatient clinic]. AB - INTRODUCTION: Adverse drug reactions is an important healthcare issue, it causes excess morbidity and mortality. The aim of this study was to determine the adverse drug reactions in patients who admitted to the outpatient clinic of respiratory diseases and to improve some clinical strategies if they are preventable. PATIENTS AND METHODS: This study is a prospective observational study which was performed to determine adverse drug reaction in patients who admitted to the outpatient clinic of respiratory diseases. RESULTS: During the 15 months of study period a total of 114 adverse reactions were reported in 92 out of 18.130 patients. Most of the adverse reactions were related with gastrointestinal system, central nervous system and cardiovascular system. The most of the adverse events were associated with fixed inhaled formoterol budesonide combination and inhaled tiotropium. The most frequently reported reactions were hoarseness, xerostomia, headache and dizziness. Poliuri and cough were less frequently reported reactions. CONCLUSION: Most of the adverse reactions were of limited intensity but some of these side effects might effect patients compliance. Serious adverse events were not detected. PMID- 22779934 TI - Management of and risk factors related to hepatotoxicity during tuberculosis treatment. AB - INTRODUCTION: Hepatotoxicity is one of the most frequent adverse events occurring during tuberculosis treatment that may negatively affect treatment compliance, clinical outcome. This study was designed to evaluate management, risk factors related to hepatotoxicity during tuberculosis treatment. PATIENTS AND METHODS: Hospitalized patients for tuberculosis treatment at Sureyyapasa Chest Diseases, and Chest Surgery Training and Research Hospital were included, between January 2004 and December 2007. Prevalence of hepatotoxicity, risk factors were evaluated among tuberculosis patients under anti-tuberculosis treatment according to World Health Organization (WHO) guideline. Hepatotoxicity was defined any elevated liver function tests with accompanying symptoms. Age, gender, past history of anti-tuberculosis treatment, extensity of radiological findings, co-morbid disorders and drug resistance were the risk factors evaluated in terms of development and recurrence of hepatotoxicity. RESULTS: Of 1443 patients (38.37 +/ 16.74 years; 64.5% were males), 106 (7.3%) was identified to develop hepatotoxicity on an average of 20 days after beginning treatment and lasting an average of 14 days. Hepatotoxicity for once in 78.3% (n= 83) of patients and more than once in 21.7% (n= 23) patients. All anti-tuberculosis drugs was continued at full dosage after the normalization of liver enzyme in 76.4% (n= 81). In recurrence a step-by-step treatment was re-started by exclusion of responsible drug/s. Treatment was administered without modification of WHO regimes in 79.2%. Pyrazinamide was omitted in 15 cases while rifampicin only in one patient. Triple drug regimen with isoniazid, ethambutol and streptomycin was used in six cases. Quinolon was added to treatment only in one patient. Presence of a co-morbidity was determined to be significant predictor of hepatotoxicity development OR= 3.093 (CI= 1.95-4.89; p= 0.000) past history of anti-tuberculosis treatment was significantly associated with recurrence (p= 0.027). There was no hepatotoxicity dependent mortality. CONCLUSION: Hepatotoxicity can be successfully management of hepatotoxicity without second line tuberculosis drugs in ongoing treatment regime. PMID- 22779935 TI - [The practice of respiratory disability assessment in a university hospital: the analysis of 136 patients]. AB - INTRODUCTION: This study, to examine the outcomes of the respiratory disability assessment in our clinic. MATERIALS AND METHODS: The reports of 136 patients who attended the chest diseases clinic between January 2010 and June 2011 for the assessment of the respiratory disability were examined retrospectively. RESULTS: Of 10.457 patients who presented in 18 months, 136 (1.3%) requested the assessment of the respiratory disability. The patients' average age was 51 +/- 12 years and 118 (87%) were male. Farmers constituted 19.8% of the patients and mine and foundry workers 10.7% of the patients. The most frequent symptoms were dyspnea (91.2%) and cough (76.5%). The most frequent radiological pattern was reticular and nodular opacities (38.2%). The workup led to a diagnosis of chronic obstructive pulmonary disease in 64 patients (47%) and of interstitial pulmonary disease/pneumoconiosis in 19 (14%) patients. No respiratory disease was found in 19 patients. Among 44 (32.4%) patients for whom disability rate was calculated, 8 (18.2%) had an incapacity rate of 60% or higher and 13 had 0%. The disability rates showed positive correlations with age, the duration of the respiratory symptoms and PaCO2 level (respectively r= 0.395, p= 0.008; r= 0.391, p= 0.009; r= 0.790, p< 0.001), and negative correlations with FVC, FEV1 and PaO2 levels (respectively r= -0.681, p< 0.001; r= -0.766, p< 0.001; r= -0.661, p= 0.003). Linear regression analysis showed that high PaCO2 value is a determinant for a high disability rate (r= 0.902, p= 0.014). Furthermore, smokers had higher disability rates than non-smokers (p< 0.001). CONCLUSION: We believe that new evidence-based guidelines that will resolve the medicolegal and social obscurities are needed. PMID- 22779936 TI - Determination of principal genotypic groups among susceptible, MDR and XDR clinical isolates of Mycobacterium tuberculosis in Belarus and Iran. AB - INTRODUCTION: All members of the Mycobacterium tuberculosis complex were assigned to one of the three principle genetic groups based on KatG463/GyrA95 polymorphism. MATERIALS AND METHODS: A total of 202 isolates of M. tuberculosis consisting of 50 susceptible, 121 MDR (multidrug resistant) and 31 XDR (extensively drug resistant) isolated from culture-confirmed tuberculosis patients in different regions of Belarus and Iran (Tehran and Markazi province). Isolates were screened by sequencing and polymerase chain reaction restriction fragment length polymorphism (RFLP) assay, and were further divided into three principal genetic groups (PGG), based on Sreevatsan's pattern as polymorphisms in KatG463/GyrA95 codons. RESULTS: Among the 104 isolates, characterized as MDR from Belarus, 57 (54.8 +/- 4.8%), 30 (28.8 +/- 4.43%), 17 (16.3 +/- 3.6), belonged to PGG 1, 2, and 3, respectively (p< 0.05). Thirty one XDR isolates from Belarus had a similar pattern as 15 (48.4%), 12 (38.7%), 4 (12.9%) PGG 1, 2, and 3, respectively. From Iranian samples, Markazi isolates (susceptible to drugs) had a pattern as 12 (36.5%), 15 (45.5%), 3 (6%), and Tehran samples were (selected MDR): 9 (53%), 6 (35.2%), 2 (11.8%) (PGG 1, 2, and 3, respectively). In a study of tuberculosis patients, who were in prison, no relation was found between PGG and resistance to isoniazid, but most of the identified isolates belonged to PGG 1 (45.5 +/- 10.9%) (p< 0.05). Overall, the group 1 isolates showed more frequency in MDR and XDR rather than susceptible strains, and there aren't any relations to geographic region. PMID- 22779937 TI - A case of newborn with community acquired pneumonia caused by Cupriavidus pauculus. AB - Cupriavidus pauculus is a gram-negative, aerobic, non-spore forming, non fermentative motile bacillus. The bacillus can be isolated from water, bottled mineral water, and water from ultrafiltration systems in hospital setting. C. pauculus rarely causes human infections, however it may be an infectious agent especially in immunocompromised individuals. In this report, we present the first case of community acquired pneumonia caused by C. pauculus in a previously healthy newborn who was hospitalized in neonatal intensive care unit on postnatal day 16 because of respiratory distress. PMID- 22779938 TI - Painless left hemorrhagic pleural effusion: an unusual presentation of leaking saccular aortic arch aneurysm. AB - Most thoracic aortic aneurysms are asymptomatic and are detected by chance on routine chest imaging for some other reasons. Only rarely it is symptomatic due to leak and dissection which is a potentially life threatening event that commonly presents with severe pain. In this report, we present the case of a 67 year-old man who presented with shortness of breath, intermittent cough, fever, and left sided painless hemorrhagic pleural effusion. Further investigation by plain radiography, computed tomography and magnetic resonance imaging revealed a saccular aneurysm arising from the lateral aspect of the mid-transverse arch of the aorta, along with a dissecting descending aortic aneurysm with false lumen communicating with left pleural space. The patient refused any surgical procedure and was treated conservatively with blood transfusions and anti hypertensive medication. On the 8th day patient finally succumb to a fatal episode of shock. We suggest dissecting thoracic aneurysm be included in the differential diagnosis of non-traumatic hemorrhagic pleural effusion in an elderly patient presenting with dysnea, cough and fever, which otherwise suggest the clinical diagnosis of bronchogenic carcinoma. Computed tomography of the chest should be immediately performed as the diagnostic procedure of choice. PMID- 22779939 TI - Central airway obstruction due to malignant fibrous histiocytoma metastasis in a case with Mounier-Kuhn syndrome. AB - Malign fibrous histiocytoma is one of the most observed soft tissue sarcomas seen in the adults. The most common metastasis region is the lung and metastasis. Mounier-Kuhn syndrome is characterized by the highly dilatation of the trachea and bronchi. We may encounter with the major airway obstruction in the endoluminal or extraluminal lung and mediastinal masses or those with both components together. In this article, we would like to highlight the occurrence of a rare seen clinical situation secondary to the giant mediastinal malign fibrous histiocytoma metastasis and the clinical difficulties experienced in resolving of the main airway obstruction caused by the mass. Since the lack of the similar studies conducted previously, we found the case worth presenting. PMID- 22779940 TI - Small cell osteosarcoma of rib: diagnosis and treatment of the rare case. AB - Small cell osteosarcomas are very rare tumors which are classified as the component of Ewing's sarcoma family. Although the tumor generally is seen on long bones, short bone involvement is rare. Moreover, rib localization is quite uncommon and to the best of our knowledge, only one case has been reported so far. Herein, we described a case of rib-localized small cell osteosarcomas which was only presented with localized left sided pain. Resection surgery followed by adjuvant chemotherapy was performed. Clinico-pathological features and therapeutic approach are discussed in the light of the relevant literature. PMID- 22779941 TI - Pulmonary involvement in sea-blue histiocytosis. AB - Sea-blue histiocytosis is one of the six types of Niemann-Pick disease. It is characterized by childhood onset of hepatosplenomegaly, lack of neurological involvement and diminished sphingomyelinase activity. Pulmonary system is rarely involved sea-blue histiocytosis. In this paper, we present a 39-years-old male who had previously diagnosed as sea-blue histiocytosis at the age of 15. He was admitted to our clinic due to productive cough, hemoptysis, fever and weight loss. His symptoms did not resolve with the antibiotic treatment and further investigations revealed pulmonary involvement of sea-blue histiocytosis. After diagnostic bronchoalveolar lavage, his symptoms were improved, interestingly. This rare entity was discussed with literature survey. PMID- 22779942 TI - [Nanoparticle: a nightmare for the future]. AB - Nanotechnology is a new discipline where 1-100 nanometers long particles are used, with an extensive field of application including physics, chemistry, electronics, energy production, biology, and medicine. Just as in every innovation, the effects of this technology and its products on environment and health are wondered. Lungs are the major port of entry and target of the nanoparticles in human body. This review will discuss, in the light of the literature, the possible adverse effects of nanoparticles on living beings and especially on respiratory system. PMID- 22779943 TI - [The effect of non-invasive mechanical ventilation in postoperative respiratory failure]. AB - Postoperative respiratory failure is related with the highest mortality and morbidity among all perioperative complications. The most common underlying mechanism of postoperative respiratory failure is the development of atelectasis. Anaesthesia, medications which cause respiratory depression, high FiO2 use, postoperative pain and disruption of muscle forces due to surgery leads to decrease in functional residual capacity and results in atelectasis formation. Atelectasis causes severe hypoxemia due to ventilation, perfusion mismatch, shunt and increased peripheral vascular resistance. Intrathoracic positive pressure is an effective therapeutic option in both prevention and treatment of atelectasis. Non-invasive mechanical ventilation is related with a lower mortality and morbidity rate due to lack of any potential complication risks of endotracheal intubation. Non-invasive mechanical ventilation can be applied as prophylactic or curative. Both of these techniques are related with lower reintubation rates, nosocomial infections, duration of hospitalization and mortality in patients with postoperative respiratory failure. The differences of this therapy from standard application and potential complications should be well known in order to improve prognosis in these group of patients. The primary aim of this review is to underline the pathogenesis of postoperative respiratory failure. The secondary aim is to clarify the optimum method, effect and complications of non-invasive mechanical ventilation therapy under the light of the studies which was performed in specific patient groups. PMID- 22779944 TI - [Salbutamol in asthma treatment: with nebulizer or inhaler?]. AB - Breath relieving and protective drugs in asthma treatment are applied through pressurized metered dose inhaler (pMDI), nebulizer or dry powder inhaler. The short acting beta-2 agonist salbutamol used in acute asthma exacerbation is found in the forms of nebule or pMDI in Turkey. Nebule form is used more frequently in emergency services. The aim of this review is to compare these two routes of administration through clinical efficacy, the amount of drug reaching to the lungs and adverse events comprehensively by way of looking through the studies. Additionally effect of different inhalation techniques through chambers, different methods used in cleaning of them and different types of nebulizers, to the efficacy are investigated. As a result, asthma exacerbation can be treated with pMDIs used through holding chambers in emergency room successfully when applied with dosing scheme appropriate for the patient's age, weight and severity of exacerbation (usually 1/4th of nebule dosing) on the contrary to ordinary method of nebulizers. PMID- 22779945 TI - A case with double vena cava superior discovered during the investigating of persistent cough. PMID- 22779946 TI - Humeral stress remodelling locations differ in Thoroughbred racehorses training and racing on dirt compared to synthetic racetrack surfaces. AB - REASONS FOR PERFORMING STUDY: Veterinarians have observed a putative change in the location of humeral stress remodelling in Thoroughbred racehorses with change from dirt to synthetic racetrack surfaces. OBJECTIVES: To determine whether the location and severity of humeral stress remodelling differs between Thoroughbred racehorses exercising on dirt and synthetic racetrack surfaces, the potential significance of different locations of stress remodelling, and the potential usefulness of scintigraphy for prevention of complete humeral fracture. METHODS: Scintigraphic images of humeri from 841 Thoroughbred racehorses at 3 racetracks during 2 years before and after conversion from dirt to synthetic surfaces were evaluated for location and severity of lesions. The effects of surface on lesion distributions were examined using Chi-square or Fisher's exact tests. Archived fractured humeri were examined to determine the location and severity of stress remodelling associated with complete fracture. Databases were queried to determine whether racehorses with scintigraphic lesions suffered humeral fracture and whether racehorses with a complete humeral fracture had had a scintigraphic examination. RESULTS: Horses at synthetic racetracks had a greater proportion of distal humeral lesions, whereas horses at dirt racetracks had a greater proportion of caudoproximal lesions (P<0.001). Proximal lesions were more likely to be severe than distal lesions (P<0.001). Most complete fractures were associated with caudoproximal lesions, which were more often severe than distal lesions (P = 0.002). None of the horses with a scintigraphic lesion had a complete humeral fracture. None of the horses with a complete humeral fracture underwent scintigraphic examination. CONCLUSIONS: Race surface affected humeral scintigraphic lesion location and hence the location of stress remodelling. Lesion severity was associated with lesion location. Complete humeral fracture was associated with caudoproximal stress remodelling and lack of scintigraphic examination. POTENTIAL RELEVANCE: Risk for complete humeral fracture may be lower on synthetic surfaces than on dirt surfaces, and, by inference, for horses examined using scintigraphy. PMID- 22779947 TI - Presurgical nasoalveolar molding (PNAM) for a unilateral cleft lip and palate: a clinical report. AB - Cleft lip and palate deformity is a congenital defect of the middle third of the face. Incidence varies from 1:500 to 1:2500 live births. Etiology depends upon hereditary and environmental factors. Restoration of these defects is important not only for functional and esthetic reasons, but also because there may be a positive psychological impact for the patient and parents. The goal of primary closure of the lip for unilateral cleft lip is to ensure a normal and symmetrical lip and nose. Presurgical infant orthopedics has been employed since the 1950s as an adjunctive neonatal therapy for the correction of cleft lip and palate. Presurgical nasoalveolar molding (PNAM) represents a paradigm shift from the traditional methods of presurgical infant orthopedics. PNAM consists of active molding of the alveolar segments as well as the surrounding soft tissues. This clinical report describes a new approach of PNAM therapy for an infant with complete unilateral cleft lip and palate showing significant reduction in cleft defect size and improved contour and topography of deformed surrounding soft tissues. PMID- 22779948 TI - Effectiveness of different click stimuli in diagnosing superior canal dehiscence using cervical vestibular evoked myogenic potentials. AB - CONCLUSION: Testing cervical vestibular evoked myogenic potential (cVEMP) in response to 90 dB nHL clicks can, in contrast to high-intensity 500 Hz tone bursts, be used as a screening test for superior canal dehiscence (SCD) syndrome. OBJECTIVES: cVEMP testing has its key clinical significance for evaluating saccular and inferior vestibular nerve function, but also for assessment of vestibular hypersensitivity to sounds in patients with SCD syndrome. The routine stimulus used in cVEMP testing is high-intensity 500 Hz tone bursts. The aim of the present study was to compare the high-intensity tone burst stimulation with less intense click stimulations for the diagnosis of SCD syndrome. METHODS: cVEMP amplitudes in response to 500 Hz tone bursts and clicks were studied in 38 patients with SCD syndrome unilaterally. RESULTS: cVEMP testing using high intensity 500 Hz tone bursts did not consistently distinguish SCD patients. This nonfunctioning of high-intensity 500 Hz stimulation is most likely due to saturation. With 90 and 80 dB nHL clicks there is low risk for saturation and both these click stimulations were effective. Testing with both 80 and 90 dB nHL clicks did not have any significant advantage over just using 90 nHL dB clicks. PMID- 22779949 TI - The conundrum of vanishing early decelerations in British obstetrics, a step backwards? Detailed appraisal of British and American classifications of fetal heart rate decelerations - fallacies of emphasis on waveform and putative aetiology. AB - A recent opinion survey of British Obstetricians revealed 'early' fetal heart rate (FHR) decelerations as the commonest type in their practice. This contrasts with the guidelines by the National Institute for Health and Clinical Excellence, UK (NICE 2007) that 'true uniform early decelerations are rare and most decelerations are variable'. This analytical review suggests that the emphasis on putative aetiology and 'waveform' of decelerations by NICE and other national guidelines leads to fundamental inconsistencies. 'Uniform shape' is misinterpretation of the description by Hon and Quilligan (1968). Truly 'uniform' (identical)) decelerations do not occur and no examples can be found. Gradual ('bell') or rapid shape has no correlation to putative causation or fetal condition. Obstetricians and midwives should seek clarification of these fallacies. The previous British practice of classifying decelerations based solely on time relationship to contractions seems most scientifically robust leading to more consistent interpretation and better discrimination of fetal status. PMID- 22779950 TI - Lead exposure, gestational hypertension and pre-eclampsia: a systematic review of cause and effect. AB - The association between lead and hypertension in adults was first identified in the early 1980's and it has since been proposed that lead may also have a role in gestational hypertension (GH). This systematic review investigates whether lead may be associated with the development of GH or pre-eclampsia. MEDLINE, Embase and Web of Science were searched from inception to August 2011, using the terms: blood lead levels, pregnancy, pregnancy induced hypertension, gestational hypertension and pre-eclampsia. Nine papers were found. Positive associations between lead and GH or pre-eclampsia were found in six studies. The development of GH or pre-eclampsia may serve as a signal to assess blood lead concentrations in pregnant women, as even low lead concentrations have been shown to negatively impact the neurodevelopment and cognitive abilities of children. Adequate calcium intake throughout the pregnancy and lactation period may assist with reducing lead exposure levels. PMID- 22779951 TI - Prednisolone for repeated implantation failure associated with high natural killer cell levels. AB - Women with unexplained repeated IVF failure present a considerable challenge. Some cases are believed to be due to immunological dysfunction preventing effective embryo implantation. As data are still being collected, doctors are faced with the dilemma of treating patients (or not) in the absence of randomised control trial evidence. This review explores a pragmatic approach in using natural killer cell analysis as a means of targeting suitable patients who might attempt treatment with additional immunosuppressive therapy. PMID- 22779952 TI - Homocysteine, folate and pregnancy outcomes. AB - The purpose of this study is to evaluate the relationship between maternal and/or cord blood folate/homocysteine concentrations and adverse pregnancy outcomes. The study population included a random sample of singleton pregnant women in whom we measured total homocysteine and folic acid in maternal or cord blood at deliveries. A total of 227 pregnant women were enrolled. The concentration of folate in maternal blood tended to be significantly lower in pre-term birth than in full-term delivery group (median (95% CI), 14.4 (3.6-73) vs 25 (7.3-105.5) p < 0.01). The total homocysteine in maternal and cord blood was significantly higher in the pre-eclampsia than in the normotensive group (7.9 (1.7-28.2) vs 5.9 (1.8 14.6) MUmol/ml, p < 0.05; and 5.8 (2.6-14.4) vs 4.2 (0.7-7.9) ng/ml, p < 0.05, respectively). Lower maternal serum folate concentration is associated with pre term delivery and higher maternal plasma homocysteine concentration with pre eclampsia. PMID- 22779953 TI - The role of homocysteine, asymmetric dimethylarginine and nitric oxide in pre eclampsia. AB - Nitric oxide (NO) contributes to vasodilatation that is observed during normal pregnancy. Hyperhomocysteinaemia (HHcy) is a vascular risk factor associated with placental microvascular diseases and pre-eclampsia. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (NOS) has been linked to endothelial dysfunction. Maternal ADMA has been reported to be higher in women with pre-eclampsia and HHcy leads to accumulation of ADMA. The aim of this presented study is to evaluate the alterations of plasma homocysteine, ADMA and NO levels in mild pre-eclampsia. A total of 40 pre eclamptic women and 40 healthy controls were included into the study. Mean systolic and diastolic blood pressure, mean serum homocysteine and ADMA levels were significantly higher and NO level was lower in patients. Serum homocysteine, ADMA and NO levels found to be correlated among them and with blood pressure. In conclusion, we found that homocysteine and ADMA levels were increased and NO levels decreased in pre-eclampsia. PMID- 22779954 TI - Prevalence and risk factors for persistent hypertension after the puerperium in pregnancies complicated with hypertensive disorders. AB - New onset hypertensive disorders arising in the second half (>20 weeks) of pregnancy may persist beyond the puerperium. Using prospective follow-up data comprising information on 198 previously normotensive-non proteinuric women who developed hypertensive disorders after 20 weeks' gestation, we examined the prevalence and risk factors for persistence of hypertension after the puerperium. The prevalence of persistent hypertension was 25.8%. Compared with normotensive women, maternal age >=35 years (OR = 14.89; 95% CI, 3.2-67.8), serum creatinine level (OR = 5.91; 95% CI,1.5-22.8), serum uric acid (OR = 37.49; 95% CI, 10.4 140.0) and maternal HIV infection (OR = 14.18; 95% CI, 1.5-132.0) were independently associated with persistent hypertension. Identification of women at risk of developing chronic hypertension after the puerperium can prevent morbidities related to hypertension. PMID- 22779955 TI - CD31 and Factor VIII in angiogenesis of normal and pre-eclamptic human placentas. AB - We aimed to evaluate normal and pre-eclamptic placental vasculature by using CD31 and Factor VIII. We evaluated placentas of 37 pre-eclamptic women by using immunohistochemical staining with CD31 and Factor VIII antibodies. Individual microvessels in the placental tissues were counted at * 100 and * 400 magnification. Microvessel counts were lower in placentas of pre-eclamptic patients compared with healthy controls after staining with CD31 (26.5 +/- 5.7 vs 103.9 +/- 8.2, p < 0.001) and Factor VIII (24.8 +/- 6.7 vs 98.7 +/- 10.3, p < 0.001). Balance between proangiogenic and antiangiogenic factors seems to be shifted in favour of anti-angiogenic factors in pre-eclampsia. PMID- 22779956 TI - Awareness and acceptance of the pandemic influenza (H1N1v 2009) vaccination among antenatal patients in a district general hospital. AB - Pandemic H1N1 influenza virus was the cause of worldwide respiratory infection in 2009. The majority of these infections were self-limiting, however, high-risk groups, including pregnant women were at increased risk of mortality and morbidity from swine flu. Because of these risks, the World Health Organization recommended that pregnant women should receive the swine flu vaccine during pregnancy. The swine flu vaccine, like the seasonal flu vaccine, is safe to use in pregnancy. In view of the obvious benefits and safety of the pandemic flu vaccine, we decided to undertake a survey to assess the awareness and uptake of the vaccine among pregnant women in our local community. In our survey, lack of counselling from healthcare providers and fears of risks from the vaccine are the main reasons for refusal. For these reasons, healthcare professionals are provided with up-to-date information about the vaccine and are asked to provide this information to pregnant women at all stages of pregnancy in order to increase their awareness and acceptance of the vaccine. PMID- 22779958 TI - Emergency caesarean section in low risk nulliparous women. AB - The rising incidence of caesarean section (CS), including emergency caesarean section (ECS) in nulliparas is of concern. Previous CS may have implications for future pregnancies and deliveries. This article describes the prevalence and indications for ECS in a cohort of low risk nulliparas and identifies maternal and fetal risk factors associated with ECS. We included 2,748 low-risk women and 8.7% had ECS. Failure-to-progress (FTP) accounted for 68.3% of the ECS and 30.4% were performed due to suspected fetal distress (SFD). Multivariate logistic regression analyses were done to estimate the association between risk factors and indications for ECS. Smoking during pregnancy (OR 2.33; CI 1.18-4.61) and BMI >= 30 (OR 2.87, CI 1.34-6.16) were associated with increased risk of ECS due to SFD. Birth weight (BW) >= 4,000 (OR 2.95; CI 1.92-4.53) and smoking cessation during pregnancy (OR 2.02; CI 1.26-3.20) were associated with increased risk of ECS due to FTP. PMID- 22779957 TI - Do amniotic fluid leptin levels decrease in pregnancies with fetal trisomy 21? AB - The objective of this study was to find a possible correlation between Down syndrome and amniotic fluid leptin. We compared 2nd trimester amniotic fluid leptin levels of fetuses with normal karyotype and with trisomy 21. We retrospectively found 15 fetuses with Down syndrome and we randomly selected 48 fetuses with normal karyotype as controls from our perinatology record database, in order to analyse their 2nd trimester amniotic fluid leptin levels. Amniotic fluid leptin levels were analysed by enzyme-linked immunosorbent assay (ELISA). The results were evaluated by Mann-Whitney U test. It was found that amniotic fluid leptin levels did not show any significant difference between amniotic fluids of fetuses with normal karyotype and those with trisomy 21 (p = 0.061). Median level of leptin was 10.06 ng/ml (range 2.10-36.69) for trisomy 21 fetuses and 14.53 ng/ml (range 2.30-67.33) for normal fetuses. In conclusion, leptin levels were not found to change in the amniotic fluids of fetuses with trisomy 21. This excludes a possible involvement of leptin in pathogenic processes associated with trisomy 21 during the fetal period and its potential employment as a diagnostic tool. PMID- 22779959 TI - Reverse breech extraction in cases of second stage caesarean section. AB - Our objective was to examine the feasibility of reverse breech extraction to disengage fetal head from the pelvis at second stage caesarean section (CS). A total of 50 consecutive women with singleton term pregnancies undergoing urgent CS at second stage were retrospectively evaluated. A total of 29 were delivered by the reverse breech manoeuvre (study group) and 21 women were delivered by the conventional approach (control group). The reverse breech extraction was successful in all cases of the study group. The mean estimated blood loss during operation, haemoglobin drop, Apgar scores at 1 and 5 min as well as cord PH were similar between the groups. The mean newborn weights were similar, 3492 +/- 426 and 3610 +/- 392 g in the study and control group, respectively. One case of an inadvertent extension of the low transverse incision was encountered in each group. Also, in three cases of the study group the incision was intentionally extended to an inverted T-shape to facilitate the manoeuvre. None of the newborns in both groups had trauma related to the extraction or were admitted to the neonatal intensive care unit. All women following CS had a low rate complication rate in the postpartum period. We conclude that reverse breech extraction seems to be feasible to disengage fetal head from the pelvis at second stage CS. Maternal and newborn complications following this manoeuvre seem to be low. PMID- 22779960 TI - Uterine pseudoaneurysm leakage may cause delayed postpartum haemorrhage: multidetector CT with angiography and transcatheter uterine arterial embolisation. AB - The aim of this retrospective case study was to evaluate the role of transcatheter arterial embolisation in the management of delayed postpartum haemorrhage due to pseudoaneurysm leakage, and present the angiographic findings with multidetector computed tomography (CT) along angiography as a diagnostic tool. Delayed postpartum haemorrhage due to pseudoaneurysm leakage was diagnosed in eight patients at our institution between October 2006 and June 2010. The mean patient age was 31.0 years and the mean parity, 2.0. Bilateral uterine arterial embolisation was performed in all patients. No additional embolisation sessions or hysterectomies were performed. Multidetector computed tomography with angiography helped to demonstrate the location and originating vessels of the pseudoaneurysm via fast and clear 3D images. Transcatheter uterine arterial embolisation is an option in haemodynamically stable patients, and it appears to be the treatment of choice. PMID- 22779961 TI - Convalescence advice following gynaecological surgery. AB - This was a survey, undertaken in the UK, which was sent to all obstetricians and gynaecologists. The aim was to establish the current advice given for activities during convalescence after commonly performed benign gynaecological surgery. Questionnaires were sent to all the obstetricians and gynaecologists working in 235 NHS hospitals in the UK. The total response rate was 30.51%. There is substantial variability in the advice for activities during convalescence following gynaecological surgery. This has enormous implications - mainly financial. The economic impact of absence from work is enormous. One extra day of sick leave given to patients has a direct cost of approximately L34 million annually. Our survey highlights the need for structured and evidence-based recommendations for convalescence activities following benign gynaecological surgery. PMID- 22779962 TI - A case study perspective on psychological outcomes after female genital mutilation. AB - Female genital mutilation (FGM) is still performed throughout Africa and in a few countries of Asia and the Middle East, affecting over 100 million females worldwide. It includes procedures that intentionally injure female external genital organs for non-medical reasons, and can have deleterious consequences for the physical, psychological and sexual lives of its victims. This paper presents three case studies illustrating the psychological and sexual consequences of FGM. Data were gathered about child and family history, employment, medical and psychiatric history, and the genital mutilation experienced. Self-report measures of self-esteem, mental health status and sexual life were also administered. The results obtained highlight the need for European professionals to develop greater knowledge about FGM and its serious consequences, especially as regards sexuality. This is particularly important given the large numbers of immigrant women now residing within EU countries. PMID- 22779963 TI - Outcome of IVF/ICSI referrals from the Royal Alexandra Hospital (level 2 infertility service) to Glasgow Royal Infirmary (level 3 infertility service). AB - In a 2-year period (2004 and 2005), 117 couples with infertility were referred from secondary care for IVF/ICSI treatment. This study describes the age, waiting times, diagnostic categories and outcomes for all couples referred. A total of 59% (69) of all couples referred conceived. Of these, 25% (29 couples) conceived spontaneously or as a result of simpler treatments and 34% (40 couples) conceived following IVF/ICSI treatment. The twin pregnancy rate following IVF/ICSI was 25% and the average waiting time from referral to treatment was 13-18 months. Couples with female factor infertility (excluding endometriosis) and couples with unexplained infertility experienced a higher spontaneous pregnancy rate while awaiting IVF/ICSI treatment, than those couples with male factor or combined infertility. However, couples with male factor or combined infertility achieved much higher success rates with IVF/ICSI treatment. PMID- 22779964 TI - Subfertility treatment in women with systemic lupus erythematosus. AB - This study comprised of 65 infertile patients with systemic lupus erythematosus (SLE). The aim was to study causes and different modalities used for the management of subfertile patients with SLE. All patients were diagnosed to have SLE according to the standard criteria of diagnosis. All patients were scheduled to expectant treatment, ovulation induction and timed intercourse, intrauterine insemination (IUI), intracytoplasmic sperm injection (ICSI). Anovulation was in 20 patients (20%), due to PCOS in 10 cases and due to other causes in three patients. A total of 28 patients (43.1%) needed laparoscopy for their work-up of infertility. Male factor for infertility was present in nine couples (16.7%). Ovulation induction and timed intercourse was adopted for a maximum 6 cycles and IUI for 3 cycles. In vitro fertilisation (IVF)/ICSI was needed in five cases using standard long agonist protocol. Four cases were complicated by significant ovarian hyperstimulation syndrome after conventional ovarian stimulation and cycles were cancelled. Pregnancy occurred in 20 women. Ovarian stimulation for ovulation induction and IVF seems to be safe and successful in well selected women with non-complicated SLE. PMID- 22779965 TI - A questionnaire survey to study the effect of colposcopy training in Europe. AB - The objective of the study was to see if colposcopy training can provide a measurable effect. A questionnaire containing 10 clinical scenarios requiring colposcopy was completed by delegates attending three colposcopy training courses in Europe. A total of 128 and 132 questionnaires were returned pre- and post training, respectively. The means and standard deviations for the number of correctly assessed scenarios were M = 4.21, SD = 1.71 at pre-training and M = 5.05, SD = 1.82 at post-training. The chi(2)-test showed a statistically significant difference in the proportions of correct answers at pre- and post training for five questions. The two factor ANOVA showed that there is a statistically significant difference between the pre- and post-training measures (F((2,124)) = 17.13, p < 0.001) although the effect of training is not the same for all three locations. Trainees' results show that there is a positive effect of training. The questionnaire may be used as a quality tool for measuring the effectiveness of training for colposcopy. PMID- 22779966 TI - Surgical management and follow-up of patients with cervical cancer: survey of gynaecological oncologists in the UK. AB - We investigated current surgical management and follow-up of women with cervical cancer focusing on treatment of recurrent disease and the use of routine imaging during follow-up among gynaecological oncologists in the UK. A questionnaire including questions regarding perioperative management of primary disease in cervical cancer, follow-up post-treatment, assessment and management of recurrent cervical cancer, was sent to 84 gynaecological oncologists. Some 87% responded. Considerable variations in surgical management and follow-up were identified. With central recurrence of cervical cancer without prior radiotherapy, 90% would recommend radiotherapy instead of an exenteration. For central recurrence in irradiated women, only three (4%) would not recommend an exenteration. In women with pelvic sidewall relapse without prior radiotherapy, 65 responders (96%) would offer radiotherapy, while in pelvic sidewall relapse post-radiation 25 (37%) would recommend pelvic sidewall resection in a specialised centre. A total of 21% used routine imaging during follow-up. The wide variation in clinical practice indicates that there is a need to establish national guidelines for surgical management and follow-up of primary and recurrent cervical cancer. PMID- 22779967 TI - Total laparoscopic hysterectomy for early stage endometrial cancer in obese and morbidly obese women. AB - This is a retrospective observational study, where we have evaluated the role of total laparoscopic hysterectomy (TLH) in obese and morbidly obese patients with early stage endometrial cancer. Our study illustrates that low conversion rates are achievable when appropriately trained surgeons undertake this procedure. All the women with high BMI were operated on laparoscopically in preference to laparotomy, unless there was an obvious contraindication such as a very large uterus or disseminated disease. We have also shown low conversation and complication rates for our patients, in particular a low rate of wound infection. This is in contrast to the high rate of wound infection and prolonged hospital stay reported for obese patients in the literature. Our study shows that TLH for endometrial cancer in obese women is feasible, safe and is likely to be cost effective and adds to the weight of evidence for its use in this condition. PMID- 22779968 TI - Central nervous system metastases from epithelial ovarian cancer. AB - The aim of the study was to assess the clinical features and prognosis in patients with epithelial ovarian cancer (EOC) metastasised to the central nervous system (CNS). A total of 15 patients were studied retrospectively. Clinical and pathological data and follow-up were analysed. It was found that at the diagnosis of primary EOC, the patients were 41-69 years old (56.6 +/- 8.3). The interval from diagnosis of primary EOC until the relapse was 2-39 months (19.1 +/- 10.5). Palliative radiotherapy was the treatment of the CNS relapse in 13 patients (86.7%). The follow-up after CNS relapse varied 0.5-15 months (4.7 +/- 4.2). At the time of retrospective analysis, none of the patients were still alive. Multifocality of the CNS metastases, the presence of synchronous extracranial metastases and locations in the brain were not associated with survival. It was concluded that the development of the CNS metastases seems to be not uncommon in patients with advanced ovarian cancer. Despite oncological treatment, they are indicators of poor prognosis, and most of the patients do not survive beyond the first year of follow-up. PMID- 22779969 TI - Primary and secondary malignant involvement of gynaecological organs at radical cystectomy for bladder cancer: review of literature and retrospective analysis of 360 cases. AB - The pathological analysis of cystectomy specimens from 360 female patients who underwent radical cystectomy for bladder cancer was retrospectively reported. The uterus was not available in 29 specimens, while one ovary was absent in 18 specimens and the two ovaries were absent in 20 specimens. Uterine involvement was observed in one case of transitional cell carcinoma, and benign uterine pathology was detected in 37 cases. All patients had normal ovaries, while the vagina was involved in 13 cases. A total of 12% of the patients had urethral involvement. None of the 29 patients, in whom the internal genitalia were totally or partially preserved, had late ovarian, vaginal or uterine recurrence at the last follow-up. Thus, the preservation of female internal genitalia in young patients undergoing radical cystectomy should be considered under strict criteria (low-grade, low-stage tumours away from the bladder neck). This will improve the quality-of-life (QoL) and the functional outcome without compromising cancer control. PMID- 22779970 TI - Listeriosis in pregnancy with placental abruption. PMID- 22779971 TI - A case of toxoplasmosis causing severe ventriculomegaly in association with reproductive immunotherapy. PMID- 22779972 TI - Clinical significance of fetal hyperechogenicities. PMID- 22779973 TI - Vesical calculus: an unusual cause of labour dystocia. PMID- 22779974 TI - A case of pulmonary oedema secondary to carboprost. PMID- 22779975 TI - A repeat B-Lynch suture for recurrent postpartum haemorrhage in a patient with factor V Leiden mutation. PMID- 22779976 TI - Suction curettage under laparoscopic vision for advanced angular pregnancy. PMID- 22779977 TI - A case of ectopic pregnancy within the tubal isthmus treated with laparoscopic salpingotomy. PMID- 22779978 TI - Torsion of a normal ovary and fallopian tube with an enlarged fibroid uterus. PMID- 22779979 TI - Acute encephalitis secondary to an ovarian teratoma. PMID- 22779980 TI - Recurrence of mature cystic teratoma at a site of incision. PMID- 22779981 TI - Infection of a lymphocyst after pelvic lymph node dissection for endocervical adenocarcinoma. PMID- 22779982 TI - Pelvic girdle pain during pregnancy and puerperium. PMID- 22779984 TI - Role of cigarette filter on the risk of oral cancer: a case-control study in a Chinese population. AB - OBJECTIVE: To determine the role of cigarette filter on the incidence risk of oral squamous cell cancer among male smokers in a Chinese population. SUBJECTS AND METHODS: A multicentric hospital-based case-control study was applied. Three hundred and nineteen male cases and 428 male controls matching for age ( +/- 3 years) were identified from January 2008 to December 2010. Detailed smoking histories were obtained by interviews. Logistic regression model was used to compare the influence of filter and non-filter cigarettes on oral cancer risk. RESULTS: The adjusted odd ratios (ORs) for oral cancer were 1.30 (95% CI 1.15, 1.48) of filter cigarette smokers, 2.06 (95% CI 1.17, 3.62) of non-filter cigarette smokers, and 1.73 (95% CI 1.33, 2.25) of mixed smokers, as compared with non-smokers. When classified current smokers according to smoking pack year, the ORs of mixed smokers were 2.27 (95% CI 1.06, 4.85) in <20 pack year, 0.81 (95% CI 0.57, 1.14) in 20-39 pack year, and 0.86 (95% CI 0.57, 1.29) in >= 40 pack year, as compared to filter cigarette smokers. CONCLUSIONS: The protective effect against oral cancer of cigarette filter was limited, restricted to smokers of small amount of smoking accumulation. For most smokers, the difference was non significant between filter and non-filter cigarettes on the risk of developing oral cancer. PMID- 22780087 TI - Sensitive detection of porcine DNA in processed animal proteins using a TaqMan real-time PCR assay. AB - A TaqMan real-time PCR method was developed for specific detection of porcine prohibited material in industrial feeds. The assay combines the use of a porcine specific primer pair, which amplifies a 79 bp fragment of the mitochondrial (mt) 12 S rRNA gene, and a locked nucleic acid (LNA) TaqMan probe complementary to a target sequence lying between the porcine-specific primers. The nuclear 18 S rRNA gene system, yielding a 77 bp amplicon, was employed as a positive amplification control to monitor the total content of amplifiable DNA in the samples. The specificity of the porcine primers-probe system was verified against different animal and plant species, including mammals, birds and fish. The applicability of the real-time PCR protocol to detect the presence of porcine mt DNA in feeds was determined through the analysis of 190 industrial feeds (19 known reference and 171 blind samples) subjected to stringent processing treatments. The performance of the method allows qualitative and highly sensitive detection of short fragments from porcine DNA in all the industrial feeds declared to contain porcine material. Although the method has quantitative potential, the real quantitative capability of the assay is limited by the existing variability in terms of composition and processing conditions of the feeds, which affect the amount and quality of amplifiable DNA. PMID- 22780088 TI - Spontaneous extradural aerocele following cardiopulmonary resuscitation - an unrecognised complication. AB - We present a case report of a 61-year-old gentleman who had a cardiac arrest and was delivered cardiopulmonary resuscitation (CPR) by a bystander. After resuscitation, he regained cardiac output and was breathing spontaneously. CT scan of the head showed spontaneous right frontal extradural aerocele with fracture of the posterior wall of the frontal sinus with no sign of head injury. We discuss the pathophysiology of this unrecognised complication due to CPR. PMID- 22780089 TI - Hard quasispherical particle models for the viscosity of solutions of protein mixtures. AB - Recently reported measurements of the viscosity of three monoclonal antibodies, their binary mixtures, and a binary mixture of an antibody and albumin over a broad range of compositions (Galush et al., J. Pharm. Sci. 2011,101, 1012) were quantitatively accounted for to within experimental uncertainty by an extension of the hard quasispherical particle model suggested by Ross and Minton (Biochem. Biophys. Res. Commun. 1977, 76, 971) and by a generalization of the hard sphere equation of Krieger and Dougherty (Trans. Soc. Rheol. 1959, 3, 137) . Further generalization of these equations to treat the concentration-dependent viscosity of self-associating proteins is suggested. PMID- 22780090 TI - Iridium-catalyzed intermolecular hydroamination of unactivated aliphatic alkenes with amides and sulfonamides. AB - The intermolecular addition of N-H bonds to unactivated alkenes remains a challenging, but desirable, strategy for the synthesis of N-alkylamines. We report the intermolecular amination of unactivated alpha-olefins and bicycloalkenes with arylamides and sulfonamides to generate synthetically useful protected amine products in high yield. Mechanistic studies on this rare catalytic reaction revealed a resting state that is the product of N-H bond oxidative addition and coordination of the amide. Rapid, reversible dissociation of the amide precedes reaction with the alkene, but an intramolecular, kinetically significant rearrangement of the species occurs before this reaction with alkene. PMID- 22780091 TI - The role of biologic agents in the management of non-infectious uveitis. AB - INTRODUCTION: Uveitis is an intriguing group of disorders characterized by inflammation of the uveal tract. Due to the potential grave consequences of the disease process, it is important to assess the various therapeutic options available for treating uveitis, and their outcomes. AREAS COVERED: This review discusses the use of conventional agents in the management of uveitis, including discussion of the molecular and clinical properties of corticosteroids, antimetabolites, calcineurin inhibitors and alkylating agents and their side effects. In addition, it also discusses the molecular and clinical properties of novel biologic agents and their side effects. Moreover, recommendations as to when biologic agents should be employed are also discussed. EXPERT OPINION: We recommend that in general (except in selected cases of Adamantiades-Behcet's disease) biologics should not be used as a first-line therapy for uveitis due to inconvenience, high cost, and potential immunosuppressive effects. However, many biologics are potent in inducing drug-free remission of uveitis and may be employed to manage recurrent diseases or diseases not responsive to conventional agents. PMID- 22780092 TI - Berberine on metabolic and cardiovascular risk factors: an analysis from preclinical evidences to clinical trials. AB - INTRODUCTION: Type 2 diabetes mellitus and hypercholesterolemia have proven to give an increased incidence of cardiovascular diseases (CVD). Recent studies have suggested that the natural alkaloid berberine could have pharmacological activities potentially useful in diabetes and hypercholesterolemia management. AREAS COVERED: The aim of this review is to evaluate the metabolic properties of the natural alkaloid berberine, and its potential application to the treatment of diabetes and CVD prevention. EXPERT OPINION: Berberine proved to be effective in improving glycemic control and lipid profile. The modern investigation on berberine pharmacological activity is actually developing and numerous scientific evidences are actually in progress and reported in international congresses. The near future perspective is the isolation or neo-synthesis of berberine analogs with a higher bioavailability. The anti-hyperlipidemic and anti-diabetic effects of berberine have to be related to markers of improvement in organ damage in humans; longer trials are needed to better evaluate the safety profile of the molecule, when administered alone or in association with other anti hyperlipidemic or anti-diabetic drugs, especially in the European population. PMID- 22780095 TI - Arene trifluoromethylation: an effective strategy to obtain air-stable n-type organic semiconductors with tunable optoelectronic and electron transfer properties. AB - Modulation of organic semiconductor band gap, electron affinities (EA), ionization potentials (IP), and reorganization energies (lambda) associated with charge transfer is critical for its applications. We report here that trifluoromethylation not only increases both IP and EA significantly as expected but also narrows the HOMO-LUMO band gaps and increases considerably the air stability of arene-based n-type organic semiconductors. The increased air stability results from relatively high EA energies and a change in oxidation mechanism. Calculated EAs and IPs show that trifluoromethylated arenes are excellent candidates for n-type semiconductor materials; though a moderate increase of inner-sphere reorganization energy (lambdai) associated with charge transfer is the penalty for the improved performance of the trifluoromethylated compounds. However, since lambdai decreases as the pi conjugation increases, a rational design to produce air-stable n-type semiconductor materials with reasonably small lambdai is simply to prepare trifluoromethylated arenes with extended pi conjugation. Furthermore, we found that structural isomerization can fine-tune the optoelectronic and electronic transfer properties of the corresponding aromatics. PMID- 22780094 TI - Assessing graphene nanopores for sequencing DNA. AB - Using all-atom molecular dynamics and atomic-resolution Brownian dynamics, we simulate the translocation of single-stranded DNA through graphene nanopores and characterize the ionic current blockades produced by DNA nucleotides. We find that transport of single DNA strands through graphene nanopores may occur in single nucleotide steps. For certain pore geometries, hydrophobic interactions with the graphene membrane lead to a dramatic reduction in the conformational fluctuations of the nucleotides in the nanopores. Furthermore, we show that ionic current blockades produced by different DNA nucleotides are, in general, indicative of the nucleotide type, but very sensitive to the orientation of the nucleotides in the nanopore. Taken together, our simulations suggest that strand sequencing of DNA by measuring the ionic current blockades in graphene nanopores may be possible, given that the conformation of DNA nucleotides in the nanopore can be controlled through precise engineering of the nanopore surface. PMID- 22780097 TI - Visible light photocatalytic degradation of RhB by polymer-CdS nanocomposites: role of the host functional groups. AB - Surface groups of the host polystyrene beads play an important role in the properties of the polymer-based nano-CdS composites in terms of the distribution, dispersion, crystal structure, pH-dependent stability of nano-CdS, and thereafter affect their photocatalytic activity. Surface modification of the host materials can be taken as an effective and general approach to mediate the structure and properties of the nanocomposite materials. PMID- 22780096 TI - Functional characterization of ether-a-go-go-related gene potassium channels in midbrain dopamine neurons - implications for a role in depolarization block. AB - Bursting activity by midbrain dopamine neurons reflects the complex interplay between their intrinsic pacemaker activity and synaptic inputs. Although the precise mechanism responsible for the generation and modulation of bursting in vivo has yet to be established, several ion channels have been implicated in the process. Previous studies with nonselective blockers suggested that ether-a-go-go related gene (ERG) K(+) channels are functionally significant. Here, electrophysiology with selective chemical and peptide ERG channel blockers (E 4031 and rBeKm-1) and computational methods were used to define the contribution made by ERG channels to the firing properties of midbrain dopamine neurons in vivo and in vitro. Selective ERG channel blockade increased the frequency of spontaneous activity as well as the response to depolarizing current pulses without altering spike frequency adaptation. ERG channel block also accelerated entry into depolarization inactivation during bursts elicited by virtual NMDA receptors generated with the dynamic clamp, and significantly prolonged the duration of the sustained depolarization inactivation that followed pharmacologically evoked bursts. In vivo, somatic ERG blockade was associated with an increase in bursting activity attributed to a reduction in doublet firing. Taken together, these results show that dopamine neuron ERG K(+) channels play a prominent role in limiting excitability and in minimizing depolarization inactivation. As the therapeutic actions of antipsychotic drugs are associated with depolarization inactivation of dopamine neurons and blockade of cardiac ERG channels is a prominent side effect of these drugs, ERG channels in the central nervous system may represent a novel target for antipsychotic drug development. PMID- 22780098 TI - Chitosan-based intragastric delivery of cefuroxime axetil: development and in vitro evaluation of mucoadhesive approach. AB - To have advantages of reduced dosing frequency, improved bioavailability and effective delivery system of Cefuroxime Axetil, a Chitosan based intragastric sustained release microbead formulation of Cefuroxime Axetil was developed. The drug delivery system was prepared by ionotropic gelation of Chitosan in presence of sodium tripolyphosphate as polyanion and optimized by box-behnken experimental design. Response surface methodology was applied to evaluate various vitro characteristics of prepared mucoadhesive microbeads. Multiple independent variables were optimized to achieve responses of interest, thereby to get the desired sustained release profile of Cefuroxime Axetil in gastric environment. PMID- 22780100 TI - A simulation study on the effect of cross-linking agent concentration for defect tolerant demolding in UV nanoimprint lithography. AB - The chemistry and composition of UV-sensitive resists are key factors determining the stress in the molded resist structure in UV nanoimprint lithography (UV-NIL) and thus the success of the process. The stress in the molded structure is mainly generated due to shrinkage of the resist in the UV curing step and also adhesion and friction at the stamp/resist interface in the subsequent demolding step. Thus, understanding of the stress generated in these steps is critical to the improvement of the process as well as the development of new UV resists. In this paper the effect of resist composition on the stress generation was studied by numerical simulations of the curing and demolding steps in UV-NIL. Parameters required for the simulation, such as resist shrinkage, Young's modulus, fracture strength, friction coefficient, crack initiation stress, and debonding energy, were determined experimentally for different resist compositions. As the cross linking agent concentration increases the fracture strength also improves. In addition, as more cross-linking agent is added to the resist composition, both shrinkage stress due to the curing and also adhesion at the stamp/resist interface increase resulting in a larger maximum local stress experienced by the resist on demolding. By normalizing the overall maximum local stress by the fracture stress of the resist, we found that there is an optimum for the cross linking agent concentration that leads to the most successful imprinting. Our finding is also corroborated by qualitative experimentations performed for UV-NIL with various resist compositions. PMID- 22780099 TI - Cortical stimulation mapping and Wada results demonstrate a normal variant of right hemisphere language organization. AB - PURPOSE: Exclusive right hemisphere language lateralization is rarely observed in the Wada angiography results of epilepsy surgery patients. Cortical stimulation mapping (CSM) is infrequently performed in such patients, as most undergo nondominant left hemisphere resections, which are presumed not to pose any risk to language. Early language reorganization is typically assumed in such individuals, taking left hemisphere epileptiform activity as confirmation of change resulting from a pathologic process. We present data from CSM and Wada studies demonstrating that right hemisphere language occurs in the absence of left hemisphere pathology, suggesting it can exist as a normal, but rare variant, in some individuals. Furthermore, these data confirm the Wada test findings of atypical dominance. METHODS: Cortical stimulation mapping data were examined for all right hemisphere surgical patients with right hemisphere speech at our center between 1974 and 2006. Of 1,209 interpretable Wada procedures, 89 patients (7.4%) had exclusive right hemisphere speech, and 21 (1.7%) of these patients underwent surgery involving the right hemisphere. Language site location was determined by examining intraoperative photographs, and site distribution was statistically compared to published findings from left hemisphere language dominant patients. KEY FINDINGS: Language cortex was identified in the right hemisphere during CSM for all patients with available data. All sites could be classified in superior or middle temporal gyri, inferior parietal lobe, or inferior frontal gyrus, all of which were common zones where language was identified in the left hemisphere dominant comparison sample. SIGNIFICANCE: Results suggest that the Wada procedure is a valid measure for identifying right hemisphere language processing without any false lateralization found in the patients mapped with CSM (i.e., a positive Wada is 100% sensitive for finding right hemisphere language sites), and that the distribution of language sites is consistent across right hemisphere and left hemisphere language dominant patients, supporting the theory that right hemisphere language can occur as a normal variant of language lateralization. PMID- 22780101 TI - Tooth development in a model reptile: functional and null generation teeth in the gecko Paroedura picta. AB - This paper describes tooth development in a basal squamate, Paroedura picta. Due to its reproductive strategy, mode of development and position within the reptiles, this gecko represents an excellent model organism for the study of reptile development. Here we document the dental pattern and development of non functional (null generation) and functional generations of teeth during embryonic development. Tooth development is followed from initiation to cytodifferentiation and ankylosis, as the tooth germs develop from bud, through cap to bell stages. The fate of the single generation of non-functional (null generation) teeth is shown to be variable, with some teeth being expelled from the oral cavity, while others are incorporated into the functional bone and teeth, or are absorbed. Fate appears to depend on the initiation site within the oral cavity, with the first null generation teeth forming before formation of the dental lamina. We show evidence for a stratum intermedium layer in the enamel epithelium of functional teeth and show that the bicuspid shape of the teeth is created by asymmetrical deposition of enamel, and not by folding of the inner dental epithelium as observed in mammals. PMID- 22780102 TI - Mitochondrial oxidative stress-induced apoptosis and radioprotection in proton irradiated rat retina. AB - There is concern about possible radiation damage to the eyes from occupational exposure and medical procedures. In this study, molecular mechanisms of proton radiation-induced oxidative damage to retinal cells were evaluated, with and without a cell-permeable superoxide dismutase (SOD) mimetic, metalloporphyrin compound (MnTE-2-PyP). Retinal mitochondria-associated genes and protein expression profiles were studied. Rats were treated with MnTE-2-PyP at 2.5 MUg/injection into one eye 1 h before irradiation. Proton irradiation was delivered to the same eye at doses of 1 or 4 Gy and assays were done at 6 h. Levels of Bax, Bcl-2 and Sod2 proteins were evaluated by Western blot and caspase 3 immunohistochemistry was performed to confirm the occurrence of apoptosis. Expression of several genes playing central roles in regulating the mitochondrial apoptotic pathway were significantly increased after radiation exposure, including Bbc3, Bax, Bak1, Bid, and Bcl2. Among genes involved in radiation induced oxidative stress, Sod2, Gpx and Ucp3 were up-regulated, whereas Ucp2 was down-regulated. In addition, irradiation caused changes in various proteins involved in apoptosis (caspase-3, Bax and Bcl2). Reduction in pro-apoptotic and increase in anti-apoptotic protein levels were documented after treatment with MnTE-2-PyP. Decreased activity of cytochrome c, which is involved in initiation of mitochondrial apoptosis, was also revealed after irradiation and MnTE-2-PyP. Data demonstrated that proton radiation induced mitochondrial apoptosis and altered mitochondrial function in retina. MnTE-2-PyP protected, or at least ameliorated, radiation-induced oxidative damage. These insights prompt further study of this compound as a potential therapeutic candidate for retinal protection against degenerative ocular damage induced by ionizing radiation. PMID- 22780104 TI - Synthesis and structure/antioxidant activity relationship of novel catecholic antioxidant structural analogues to hydroxytyrosol and its lipophilic esters. AB - A large panel of novel catecholic antioxidants and their fatty acid or methyl carbonate esters has been synthesized in satisfactory to good yields through a 2 iodoxybenzoic acid (IBX)-mediated aromatic hydroxylation as the key step. The new catechols are structural analogues of naturally occurring hydroxytyrosol (3,4 DHE). To evaluate structure/activity relationships, the antioxidant properties of all catecholic compounds were evaluated in vitro by ABTS assay and on whole cells by DCF fluorometric assay and compared with that of the corresponding already known hydroxytyrosyl derivatives. Results outline that all of the new catechols show antioxidant capacity in vitro higher than that of the corresponding hydroxytyrosyl derivatives. Less evident positive effects have been detected in whole cells experiments. Cytotoxicity experiments, using MTT assay, on a representative set of compounds evidenced no influence in cell survival. PMID- 22780105 TI - Salivary proteome modifications associated with periodontitis in obese patients. AB - AIM: To identify changes in the salivary protein/peptide profiles by differential proteomics in obese patients with or without periodontitis. MATERIAL AND METHODS: Periodontal examinations and whole saliva samples were obtained from 38 obese patients (mean age: 45.1 +/- 7.3 years, mean BMI: 49.3 +/- 9 kg/m(2) ) including 13 periodontitis and 25 non-periodontitis subjects, and 19 healthy controls (mean age: 44.2 +/- 6.4 years, mean BMI: 21.5 +/- 2.1 kg/m(2) ). Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) was used to compare the whole saliva polypeptide profiles. RESULTS: The SELDI-TOF-MS analysis detected eight putative markers. Six of them were increased and identified in obese subjects versus controls (albumin, alpha and beta haemoglobin chains, alpha-defensins 1, 2 and 3). Alpha-defensins were less abundant in saliva of periodontitis obese patients (36.47 +/- 19.84 MUA) versus non-periodontitis obese patients (43.44 +/- 30.34 MUA), whereas alpha-defensins were more abundant in obese patients (40.99 +/- 26.66 MUA) versus controls (27.1 +/- 23.98 MUA). CONCLUSIONS: Periodontal status modifies the salivary proteome in obese patients. Alpha-defensins may play a role in gingival inflammation, and be involved in the higher susceptibility of obese patients to periodontal diseases. PMID- 22780106 TI - Single particle inductively coupled plasma-mass spectrometry: a performance evaluation and method comparison in the determination of nanoparticle size. AB - Sizing engineered nanoparticles in simple, laboratory systems is now a robust field of science; however, application of available techniques to more complex, natural systems is hindered by numerous challenges including low nanoparticle number concentrations, polydispersity from aggregation and/or dissolution, and interference from other incidental particulates. A new emerging technique, single particle inductively coupled plasma-mass spectrometry (spICPMS), has the potential to address many of these analytical challenges when sizing inorganic nanoparticles in environmental matrices. However, to date, there is little beyond the initial feasibility studies that investigates the performance characteristics and validation of spICPMS as a nanoparticle sizing technique. This study compares sizing of four silver nanoparticle dispersions (nominal diameters of 40, 60, 80, and 100 nm) by spICPMS to four established sizing techniques: dynamic light scattering, differential centrifugal sedimentation, nanoparticle tracking analysis, and TEM. Results show that spICPMS is able to size silver nanoparticles, across different sizes and particle number concentrations, with accuracy similar to the other commercially available techniques. Furthermore, a novel approach to evaluating particle coincidence is presented. In addition, spICPMS size measurements were successfully performed on nanoparticles suspended in algal growth media at low concentrations. Overall, while further development of the technique is needed, spICPMS yields important advantages over other techniques when sizing nanoparticles in environmentally relevant media. PMID- 22780103 TI - Murine P-glycoprotein deficiency alters intestinal injury repair and blunts lipopolysaccharide-induced radioprotection. AB - P-glycoprotein (P-gp) has been reported to increase stem cell proliferation and regulate apoptosis. Absence of P-gp results in decreased repair of intestinal epithelial cells after chemical injury. To further explore the mechanisms involved in the effects of P-gp on intestinal injury and repair, we used the well characterized radiation injury model. In this model, injury repair is mediated by production of prostaglandins (PGE(2)) and lipopolysaccharide (LPS) has been shown to confer radioprotection. B6.mdr1a(-/-) mice and wild-type controls were subjected to 12 Gy total body X-ray irradiation and surviving crypts in the proximal jejunum and distal colon were evaluated 3.5 days after irradiation. B6.mdr1a(-/-) mice exhibited normal baseline stem cell proliferation and COX dependent crypt regeneration after irradiation. However, radiation induced apoptosis was increased and LPS-induced radioprotection was blunted in the C57BL6.mdr1a(-/-) distal colon, compared to B6 wild-type controls. The LPS treatment induced gene expression of the radioprotective cytokine IL-1alpha, in B6 wild-type controls but not in B6.mdr1a(-/-) animals. Lipopolysaccharid-induced radioprotection was absent in IL-1R1(-/-) animals, indicating a role for IL 1alpha in radioprotection, and demonstrating that P-gp deficiency interferes with IL-1alpha gene expression in response to systemic exposure to LPS. PMID- 22780107 TI - Comparison of a novel fixation device with standard suturing methods for spinal cord stimulators. AB - INTRODUCTION: Spinal cord stimulation is a well-established treatment for chronic neuropathic pain of the trunk or limbs. Currently, the standard method of fixation is to affix the leads of the neuromodulation device to soft tissue, fascia or ligament, through the use of manually tying general suture. A novel semiautomated device is proposed that may be advantageous to the current standard. Comparison testing in an excised caprine spine and simulated bench top model was performed. MATERIALS AND METHODS: Three tests were performed: 1) perpendicular pull from fascia of caprine spine; 2) axial pull from fascia of caprine spine; and 3) axial pull from Mylar film. Six samples of each configuration were tested for each scenario. Standard 2-0 Ethibond was compared with a novel semiautomated device (Anulex fiXate). Upon completion of testing statistical analysis was performed for each scenario. RESULTS: For perpendicular pull in the caprine spine, the failure load for standard suture was 8.95 lbs with a standard deviation of 1.39 whereas for fiXate the load was 15.93 lbs with a standard deviation of 2.09. For axial pull in the caprine spine, the failure load for standard suture was 6.79 lbs with a standard deviation of 1.55 whereas for fiXate the load was 12.31 lbs with a standard deviation of 4.26. For axial pull in Mylar film, the failure load for standard suture was 10.87 lbs with a standard deviation of 1.56 whereas for fiXate the load was 19.54 lbs with a standard deviation of 2.24. CONCLUSIONS: These data suggest a novel semiautomated device offers a method of fixation that may be utilized in lieu of standard suturing methods as a means of securing neuromodulation devices. Data suggest the novel semiautomated device in fact may provide a more secure fixation than standard suturing methods. PMID- 22780108 TI - CD36 inhibition prevents lipid accumulation and contractile dysfunction in rat cardiomyocytes. AB - An increased cardiac fatty acid supply and increased sarcolemmal presence of the long-chain fatty acid transporter CD36 are associated with and contribute to impaired cardiac insulin sensitivity and function. In the present study we aimed at preventing the development of insulin resistance and contractile dysfunction in cardiomyocytes by blocking CD36-mediated palmitate uptake. Insulin resistance and contractile dysfunction were induced in primary cardiomyocytes by 48 h incubation in media containing either 100 nM insulin (high insulin; HI) or 200 MUM palmitate (high palmitate; HP). Under both culture conditions, insulin stimulated glucose uptake and Akt phosphorylation were abrogated or markedly reduced. Furthermore, cardiomyocytes cultured in each medium displayed elevated sarcolemmal CD36 content, increased basal palmitate uptake, lipid accumulation and decreased sarcomere shortening. Immunochemical CD36 inhibition enhanced basal glucose uptake and prevented elevated basal palmitate uptake, triacylglycerol accumulation and contractile dysfunction in cardiomyocytes cultured in either medium. Additionally, CD36 inhibition prevented loss of insulin signalling in cells cultured in HP, but not in HI medium. In conclusion, CD36 inhibition prevents lipid accumulation and lipid-induced contractile dysfunction in cardiomyocytes, but probably independently of effects on insulin signalling. Nonetheless, pharmacological CD36 inhibition may be considered as a treatment strategy to counteract impaired functioning of the lipid-loaded heart. PMID- 22780109 TI - Interaction of a calcium channel blocker with noise in cochlear function in guinea pig. AB - CONCLUSIONS: Both nifedipine and noise exposure had damaging effects on cochlear function. These damaging effects were subtractive rather than additive, suggesting that calcium channel blockers may have a protective role in noise induced hearing loss. OBJECTIVE: We assessed the interaction of nifedipine, a calcium channel blocker, with noise in cochlear function by evaluating changes in the compound action potential (CAP) threshold after the administration of nifedipine with or without noise exposure. METHODS: Eighty guinea pigs were randomly assigned to eight groups based on those with cochlear perfusion with nifedipine only (0, 0.15, 0.5, and 3 uM, groups 1-4) and noise exposure (groups 5 8). CAP thresholds were recorded using a round window electrode before and 120 min after cochlear perfusion. RESULTS: Cochlear perfusion of different concentrations of nifedipine caused 2.5, 5.5, 28, and 21.5 dB SPL threshold shift, respectively, at 0, 0.15, 0.5, and 3 uM concentrations (groups 1-4). In comparison, the CAP thresholds after nifedipine perfusion with noise exposure were 43.5, 46.5, 20, and 21.5 dB SPL, respectively, in groups 5-8. PMID- 22780111 TI - Medicalization of dying: are we turning the corner? PMID- 22780113 TI - Heroism and the fear of death. PMID- 22780112 TI - Dyspnea review for the palliative care professional: treatment goals and therapeutic options. PMID- 22780114 TI - Ketamine: a real-world experience in cancer pain. PMID- 22780115 TI - Response to ketamine article. PMID- 22780116 TI - Protecting physicians providing palliative care consistent with patient wishes. PMID- 22780117 TI - Pharmacologic treatment of acute venous thromboembolism in patients with advanced cancer #236. PMID- 22780118 TI - Complicated grief #254. PMID- 22780119 TI - Crossing over... PMID- 22780120 TI - Bad things come in threes. PMID- 22780121 TI - The politics of palliative care: a way forward? PMID- 22780195 TI - Autologous point-of-care cellular therapies variably induce equine mesenchymal stem cell migration, proliferation and cytokine expression. AB - REASONS FOR PERFORMING STUDY: Autologous cellular therapy products including adipose-derived stromal vascular fraction (SVF), bone marrow mononuclear cells (BMMNs), cord blood mononuclear cells (CBMNs) and platelet rich plasma are options for treatment of acute orthopaedic lesions while mesenchymal stem cells (MSCs) are culture expanded. These products may contribute to healing by secreting matrix proteins or growth factors, but they may also act on endogenous MSCs to facilitate healing. OBJECTIVES: To determine the effects of cell therapy products on MSCs function in vitro. The hypothesis was that cell therapy products promote MSCs functions including proliferation, migration and mediator release. METHODS: Fat, bone marrow (BM), cord blood and platelets were obtained from 6 Quarter Horses. The BM-MSCs and their autologous cell therapy products were co incubated in transwells. Mesenchymal stem cells proliferation, migration, gene expression and cytokine concentrations were determined. RESULTS: All cell therapy products increased MSCs proliferation, but SVF induced significantly more proliferation than any other product. Also SVF elicited more MSCs chemotaxis and, along with BMMNs, significantly more MSCs chemoinvasion. Cord blood mononuclear cells stimulated MSCs to produce high concentrations of interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-beta1), and prostaglandin E(2) (PGE(2)). Stromal vascular fraction and platelet lysate did not stimulate MSCs but SVF and platelet lysate themselves contained high concentrations of PGE(2) and IL-6 (SVF) and TGF-beta1 (platelet lysate). CONCLUSIONS: Autologous cell products variably stimulate MSCs functions with 2 primary patterns apparent. Products either contained preformed mediators that may have intrinsic healing function, or products stimulated MSCs to secrete mediators. POTENTIAL RELEVANCE: The specific clinical indications for these products may differ to include administration as a sole treatment modality prior to MSCs injection for intrinsic cell and cytokine activity (i.e. SVF) or administration concurrently with MSCs to activate MSCs for treatment of chronic lesions (i.e. CBMNs). PMID- 22780124 TI - Genome-wide association study of a quantitative disordered gambling trait. AB - Disordered gambling is a moderately heritable trait, but the underlying genetic basis is largely unknown. We performed a genome-wide association study (GWAS) for disordered gambling using a quantitative factor score in 1312 twins from 894 Australian families. Association was conducted for 2 381 914 single-nucleotide polymorphisms (SNPs) using the family-based association test in Merlin followed by gene and pathway enrichment analyses. Although no SNP reached genome-wide significance, six achieved P-values < 1 * 10(-5) with variants in three genes (MT1X, ATXN1 and VLDLR) implicated in disordered gambling. Secondary case-control analyses found two SNPs on chromosome 9 (rs1106076 and rs12305135 near VLDLR) and rs10812227 near FZD10 on chromosome 12 to be significantly associated with lifetime Diagnostic and Statistical Manual of Mental Disorders, fourth edition pathological gambling and South Oaks Gambling Screen classified probable pathological gambling status. Furthermore, several addiction-related pathways were enriched for SNPs associated with disordered gambling. Finally, gene-based analysis of 24 candidate genes for dopamine agonist-induced gambling in individuals with Parkinson's disease suggested an enrichment of SNPs associated with disordered gambling. We report the first GWAS of disordered gambling. While further replication is required, the identification of susceptibility loci and biological pathways will be important in characterizing the biological mechanisms that underpin disordered gambling. PMID- 22780196 TI - Reduced quality of life in living kidney donors: association with fatigue, societal participation and pre-donation variables. AB - Health related quality of life (HRQoL) of living kidney donors on average is good, but some donors experience a low HRQoL after donation. This study assessed the prevalence of reduced HRQoL and explored associations with pre- and post donation variables. 316 donors (response rate 74%) who donated a kidney between 1997 and 2009 filled in a questionnaire. HRQoL was measured using the Short-Form 36; fatigue using the Multidimensional Fatigue Inventory; societal participation using the Utrecht Scale for Evaluation of Rehabilitation-Participation. Donors on average had better HRQoL than the general population. However, 12% had a reduced physical (PCS) and 18% a reduced mental (MCS) HRQoL. Donors with reduced HRQoL reported greater fatigue (P < 0.01), lower societal participation (P < 0.01) and showed a trend towards statistical significance in experiencing more donor recipient relationship changes (P = 0.07). Prior to donation, donors with reduced PCS had a higher BMI (P < 0.05) and more often smoked (P < 0.05). Donors with reduced MCS had higher expectations (P < 0.05). Reduced HRQoL is associated with higher BMI, smoking and higher expectations prior to donation. These results may be used to develop a screening instrument to select donors at high risk for reduced HRQoL. PMID- 22780197 TI - (1)H NMR-based metabonomic profiling of rat serum and urine to characterize the subacute effects of carbamate insecticide propoxur. AB - Carbamate insecticide propoxur is widely used in agriculture and public health programs. To prevent adverse health effects arising from exposure to this insecticide, sensitive methods for detection of early stage organismal changes are necessary. We present here an integrative metabonomic approach to investigate toxic effects of pesticide in experimental animals. Results showed that propoxur even at low dose levels can induce oxidative stress, impair liver function, enhance ketogenesis and fatty acid beta-oxidation, and increase glycolysis, which contribute to the hepatotoxocity. These findings highlight the applicability of (1)H NMR spectroscopy and multivariate statistics in elucidating the toxic effects of propoxur. PMID- 22780199 TI - Capillary and Coulombic effects on the gas phase structure of electrosprayed concanavalin A ions and its clusters C(n)(+z) (n = 1-6). AB - Ion mobility spectrometry (IMS) coupled to mass spectrometry (MS) is used to study the gas phase collision cross section Omega(z, n) in CO(2) of multimers C(n) (n = 1-4, 6) of concanavalin A, whose tetramer C(4) has a crystal structure resembling four tetrahedrically arranged globules. C(n)(+z) ions electrosprayed from aqueous solutions of triethylammonium formate (Et(3)AF) are moderately charged (up to z = 6 and 17 for n = 1 and 6) and produce narrow mobility peaks. Charge states down to z = 1 obtained with a charge-reducing radioactive (63)Ni source are studied for the dimer and the tetramer via pure IMS (no MS). The mobilities are independent of pH in the range 6-8, controlled by addition of triethylamine to the Et(3)AF. The measured compactness group Omega(z, n)/n(2/3) is practically independent of n and z, whereas mobility calculations with clusters of touching spheres show that it should vary with n by 20-30% for a variety of scattering models. This contrast suggests that, irrespective of ambiguities on the scattering model, all multimers adopt globular shapes, precluding in particular a tetrahedral tetramer. Acetic acid solutions (87 mM aqueous) yield ions with substantially higher z, mostly with broad mobility distributions. Exceptionally high z tetramers (z = 25-29) and trimers have narrowly defined mobilities with compact but nonspherical shapes. Addition of 2-4 mM Et(3)AF to the 87 mM aqueous acetic acid solution yields narrowly defined mobilities almost identical at all z values to those from the Et(3)AF buffer, although with higher charge states showing also a transition to nonspherical shapes. We conclude that all gas phase clusters charged below a Rayleigh-like charge, z(R), are globular without regard to solution conditions, some undergoing a sharp shape transition at a critical z = z(R). We confirm that gas phase protein cross sections differ from those expected from the crystal structure, with a trend to compact probably driven by their high surface energy (and opposed by Coulombic stresses). The Rayleigh-like shape transitions seen are similar to those arising in linear homopolymers, although not as sharply defined. They yield a surface energy for protein matter almost as high as the surface tension of water. This quantitative conclusion is corroborated by prior data on cytochrome c and apomyoglobin (also showing a critical shape transition) as well as measurements of the maximum charge versus mass in aggregates of dipeptides. PMID- 22780198 TI - O-Nucleoside, S-nucleoside, and N-nucleoside probes of lumazine synthase and riboflavin synthase. AB - Lumazine synthase catalyzes the penultimate step in the biosynthesis of riboflavin, while riboflavin synthase catalyzes the last step. O-Nucleoside, S nucleoside, and N-nucleoside analogues of hypothetical lumazine biosynthetic intermediates have been synthesized in order to obtain structure and mechanism probes of these two enzymes, as well as inhibitors of potential value as antibiotics. Methods were devised for the selective cleavage of benzyl protecting groups in the presence of other easily reduced functionality by controlled hydrogenolysis over Lindlar catalyst. The deprotection reaction was performed in the presence of other reactive functionality including nitro groups, alkenes, and halogens. The target compounds were tested as inhibitors of lumazine synthase and riboflavin synthase obtained from a variety of microorganisms. In general, the S nucleosides and N-nucleosides were more potent than the corresponding O nucleosides as lumazine synthase and riboflavin synthase inhibitors, while the C nucleosides were the least potent. A series of molecular dynamics simulations followed by free energy calculations using the Poisson-Boltzmann/surface area (MM PBSA) method were carried out in order to rationalize the results of ligand binding to lumazine synthase, and the results provide insight into the dynamics of ligand binding as well as the molecular forces stabilizing the intermediates in the enzyme-catalyzed reaction. PMID- 22780201 TI - 2,6-Diazasemibullvalenes: synthesis, structural characterization, reaction chemistry, and theoretical analysis. AB - A series of 2,6-diazasemibullvalenes (NSBVs) were synthesized and isolated from the reaction of 1,4-dilithio-1,3-dienes with nitriles via oxidant-induced C-N bond formation. For the first time, the activation barrier and an X-ray crystal structure of a substituted 2,6-diazasemibullvalene were determined. All NSBVs show extremely rapid aza-Cope rearrangement in solution, but the rapid aza-Cope rearrangement is "frozen" in the solid state, as shown by solid-state NMR measurements and X-ray single-crystal structural analysis. Insertion of unsaturated compounds or a low-valent metal center into the NSBV C-N bond gave diverse and interesting ring-expansion products. Theoretical analysis showed that the localized structure is predominant and that the homoaromatic delocalized structure exists as a minor component in the equilibrium. PMID- 22780200 TI - Dyadic coping in Latino couples: validity of the Spanish version of the Dyadic Coping Inventory. AB - This study seeks to validate the Spanish version of the Dyadic Coping Inventory (DCI) in a Latino population with data from 113 heterosexual couples. Results for both partners confirm the factorial structure for the Spanish version (Subscales: Stress Communication, Emotion- and Problem-Focused Supportive, Delegated, and Negative Dyadic Coping, Emotion- and Problem-Focused Common Dyadic Coping, and Evaluation of Dyadic Coping; Aggregated Scales: Dyadic Coping by Oneself and by Partner) and support the discriminant validity of its subscales and the concurrent, and criterion validity of the subscales and aggregated scales. These results do not only indicate that the Spanish version of the DCI can be used reliably as a measure of coping in Spanish-speaking Latino couples, but they also suggest that this group relies on dyadic coping frequently and that this type of coping is associated with positive relationship functioning and individual coping. Limitations and implications are discussed. PMID- 22780202 TI - Viscoelasticity of thin biomolecular films: a case study on nucleoporin phenylalanine-glycine repeats grafted to a histidine-tag capturing QCM-D sensor. AB - Immobilization of proteins onto surfaces is useful for the controlled generation of biomolecular assemblies that can be readily characterized with in situ label free surface-sensitive techniques. Here we analyze the performance of a quartz crystal microbalance with dissipation monitoring (QCM-D) sensor surface that enables the selective and oriented immobilization of histidine-tagged molecules for morphological and interaction studies. More specifically, we characterize monolayers of natively unfolded nucleoporin domains that are rich in phenylalanine-glycine repeats (FGRDs). An FGRD meshwork is thought to be responsible for the selectivity of macromolecular transport across the nuclear pore complex between the cytosol and the nucleus of living cells. We demonstrate that nucleoporin FGRD films can be formed on His-tag Capturing Sensors with properties comparable to a previously reported immobilization platform based on supported lipid bilayers (SLB). Approaches to extract the film thickness and viscoelastic properties in a time-resolved manner from the QCM-D response are described, with particular emphasis on the practical implementation of viscoelastic modeling and a detailed analysis of the quality and reliability of the fit. By comparing the results with theoretical predictions for the viscoelastic properties of polymer solutions and gels, and experimental data from an atomic force microscopy indentation assay, we demonstrate that detailed analysis can provide novel insight into the morphology and dynamics of FG repeat domain films. The immobilization approach is simple and versatile, and can be easily extended to other His-tagged biomolecules. The data analysis procedure should be useful for the characterization of other ultrathin biomolecular and polymer films. PMID- 22780203 TI - Advanced therapies for hemophilia: reality or fantasy? PMID- 22780204 TI - 'First do no harm': where do we stand on unrelated hematopoietic cell donor safety? PMID- 22780206 TI - Bridging the gap in hematological malignancies. AB - After the success of the BTG Series in Singapore in 2010 and 2011, meeting organizers held the 3rd International Hematologic Malignancies Conference in Hong Kong. Held on 23-25 February, the BTG meeting provided an opportunity to further scientific discourse in the Asia-Pacific region. Featuring the world-renowned medical faculty and an abundance of discussion forums, the conference provided attendees the opportunity to interact with field leaders and exposed them to the latest research. The BTG conferences focus on hematologic malignancies, especially leukemia, lymphoma and myeloma. The BTG series provides an exceptional platform for the exchange of ideas for the Asia-Pacific hematology oncology healthcare community. It offers many novel opportunities for practicing physicians as well as fellows in training to meet with the world thought leaders. The annual conference brings together key opinion leaders from the Asia-Pacific region, the USA and Europe. The underlying motto is to bring the continents together and generate a global community in the quest against cancer. BTG recognizes the contributions of the Asia-Pacific physicians who are among the world leaders and gives the younger generation opportunities to present their work in a world arena. PMID- 22780207 TI - Diagnosis, progression patterns and prognostication in mastocytosis. AB - Mastocytosis is a heterogeneous group of disorders defined by abnormal growth and accumulation of clonal mast cells. CM is the predominant variant in childhood, whereas the majority of adult patients present with systemic mastocytosis. In over 80% of the latter patients, the KIT mutation D816V is detectable. Whereas childhood mastocytosis often resolves spontaneously before adolescence and has a good prognosis, in most adult patients mastocytosis is a persistent systemic disorder. The course and prognosis in these patients are variable; in indolent variants, the clinical course remains stable over years or even decades. In advanced mastocytosis, the prognosis is less favorable despite novel drugs counteracting growth of neoplastic mast cells. Although WHO criteria are clearly separating prognostic subsets of mastocytosis, little is known about specific prognostic factors predicting the outcome in individual patients. In this article, we review current concepts in mastocytosis, including prognostic parameters for indolent and advanced systemic mastocytosis. PMID- 22780208 TI - Clinical management of the hypereosinophilic syndromes. AB - Hypereosinophilic syndromes (HESs) are rare disorders characterized by marked hypereosinophilia that is directly responsible for organ damage or dysfunction. Different pathogenic mechanisms have been discovered in patient subgroups leading to the characterization of myeloproliferative and lymphocytic disease variants. In the updated terminology, idiopathic HES is now restricted to patients with HES of undetermined etiology. The practical clinical approach of patients with the different HES variants is reviewed herein, focusing on specific diagnostic tools and therapeutic options. Corticosteroids, hydroxyurea and IFN-alpha remain the classical agents for treatment of most patients with HESs. The specific role of therapeutic compounds that have become available more recently, namely, tyrosine kinase inhibitors and IL-5 antagonists, is discussed. PMID- 22780209 TI - Defibrotide for the treatment of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation. AB - Hepatic veno-occlusive disease (VOD) is a serious complication of stem cell transplantation in children. VOD is characterized by rapid weight gain, hepatomegaly, hyperbilirubinemia and ascites. The pathogenesis of VOD is thought to involve chemotherapy and radiation-induced damage to the sinusoidal endothelium, resulting in endothelial injury, microthrombosis, subendothelial damage and cytokine activation. These processes lead to concomitant progressive hepatocellular dysfunction and subsequent fluid retention and renal impairment. Severe VOD is typically associated with multiorgan failure and high mortality. A number of possible strategies for the prevention and/or treatment of VOD in children have been investigated. The most promising agent to date is defibrotide, a novel polydeoxyribonucleotide with fibrinolytic properties but no major bleeding risk. Numerous studies, including Phase II/III trials, have shown clinical benefit in pediatric patients with the use of defibrotide treatment and prophylaxis. This review discusses VOD in children and focuses on therapeutic options, including defibrotide, in this patient population. PMID- 22780210 TI - Novel approaches to the treatment of sickle cell disease: the potential of histone deacetylase inhibitors. AB - Sickle cell disease (SCD) is a severe genetic disorder of hemoglobin causing vaso occlusion. Patients suffer severe anemia, strokes, renal failure, pulmonary compromise and shortened life expectancy. Over 90,000 people in the USA have SCD, and the options for therapy are limited and only partially effective. With the available therapies - hydroxyurea, blood transfusion, hydration and pain medicines - patients continue to suffer the long-term complications of the disease. This review focuses on the pathogenesis of SCD and the role of fetal hemoglobin in disrupting the polymerization of sickle hemoglobin. The authors review the compounds that induce fetal hemoglobin: hydroxyurea, which is currently US FDA approved, and the histone deacetylase inhibitors and discuss their role in the treatment of SCD and other beta-hemoglobinopathies. PMID- 22780211 TI - Emerging targeted therapies in myelofibrosis. AB - Conventional drugs for myelofibrosis are driven by clinical needs, primarily anemia and splenomegaly. With these therapies, stem cell transplantation remains the only potentially curative approach. The discovery that mutations affecting JAK2 or MPL lead to activation of the intracellular JAK-STAT signaling pathway, and that other mutations (TET2, EZH2, ASXL1, IDH1 and IDH2) interfere with the normal machinery of epigenetics, has prompted to the development of therapies targeted at controling the major disease mechanisms. JAK2 ATP competitive inhibitors (ruxolitinib, lestaurtinib, SAR302503, SB1518 and CYT387) or drugs that indirectly inhibit the JAK-STAT pathway (everolimus) have documented major effects on splenomegaly and its constitutional symptoms. Epigenetic drugs (demethylating agents and histone deacetylase inhibitors) have displayed only minor effects on the disease symptoms. Relenting disease progression remains an unmet clinical need. PMID- 22780212 TI - EPHA3 as a novel therapeutic target in the hematological malignancies. AB - The Eph receptors are the largest family of tyrosine kinases and are of increasing interest in developmental therapeutics. Their unique method of interaction with their ligands, the ephrins, via bidirectional signaling, and their variable expression in different tissues are well documented. Ephs are upregulated in, and critical to, embryological processes, most notably development of the neurological system. They are central in many processes involving cell motility and adhesion. Recent findings on elevated expression of Eph receptors in human malignancies as well as in stem cell environments are of particular interest. With increasing focus on molecularly targeted anticancer therapies, exploration of the potential of Eph receptors as therapeutic targets in both solid and hematologic malignancies has begun. The most promising of the Eph receptors in this regard is EPHA3, which is overexpressed in many hematologic malignancies. Preclinical data support the value of pursuing this target for further development, and lead compounds are now entering the clinic. PMID- 22780213 TI - Signaling pathways activated by the B-cell receptor in chronic lymphocytic leukemia. AB - Over the past decade, several features of the B-cell receptor (BCR) complex have emerged as major markers for prognostic classification of B-cell chronic lymphocytic leukemia (B-CLL). In particular, the absence of somatic mutations within the immunoglobulin variable heavy chain genes (IGHV), the presence of ZAP 70 and a higher ability of the BCR to translate signals within the cell have been associated with an aggressive clinical course. Indeed, the stratification of patients with B-CLL based on BCR features suggests that heterogeneity of B-CLL clinical courses may reflect BCR signaling differences that have arisen during the evolution of leukemia. Therefore, characterizing BCR signaling profiles may help to identify signaling markers useful for patient stratification, disease monitoring and therapeutic targeting in B-CLL. PMID- 22780215 TI - Prevalence of upper aerodigestive symptoms in patients who underwent thyroidectomy with and without the use of intraoperative laryngeal nerve monitoring. AB - BACKGROUND: Upper aerodigestive symptoms (UADS) have been reported by patients who have had thyroidectomies. This study evaluated the long-term prevalence of UADS after thyroidectomy in patients who did and who did not have intraoperative neuromonitoring (IONM). METHODS: This was a cross-sectional study of patients with normal vocal fold mobility who had a thyroidectomy. It included patients who did and did not have this surgery with IONM. All patients answered a questionnaire regarding UADS occurring one or more years after thyroidectomy. The questionnaire dealt with UADS relating to voice and swallowing symptoms and sought to quantify their severity. The 208 patients who underwent thyroidectomy without IONM were designated the control group (CG). The 100 patients who underwent thyroidectomy with IONM were designated the neuromonitored group (NMG). RESULTS: The proportion of patients in the CG who reported UADS was 45%; 25.9% of these patients reported voice symptoms, and 33.6% reported swallowing symptoms. The proportion of patients in the NMG who reported UADS was 39%; 27% of these patients reported voice symptoms, and 22% reported swallowing symptoms. Thus, patients in the CG had more swallowing symptoms and a greater severity of UADS related symptoms than patients in the NMG. CONCLUSIONS: In this study, IONM had a favorable effect in terms of decreasing the prevalence and severity of UADS occurring one year or more after thyroidectomy. PMID- 22780216 TI - Purification and characterization of prophenoloxidase from Galleria mellonella L. AB - Prophenoloxidase (PPO) was purified from Galleria mellonella L. A 67-fold purification of the proenzyme with 352% yield was achieved by using a Sepharose 4B-L-tyrosine-p-amino benzoic acid affinity column. The purified enzyme was migrated as a single band on SDS-polyacrylamide gel electrophoresis. K(m) and V(max) values were 0.017 M and 1430.45 EU for catechol. Inhibition of PPO was investigated with inhibitors such as p-aminobenzoic acid, etyleneglycol, and ascorbic acid. Among them, ascorbic acid showed the strongest inhibitory activity with IC(50) value of 2.94 MUM. The current paper represents new strategies for the biological control of the Galleria mellonella L. insect. PMID- 22780217 TI - Dislocations and grain boundaries in two-dimensional boron nitride. AB - A new dislocation structure-square-octagon pair (4|8) is discovered in two dimensional boron nitride (h-BN), via first-principles calculations. It has lower energy than corresponding pentagon-heptagon pairs (5|7), which contain unfavorable homoelemental bonds. On the basis of the structures of dislocations, grain boundaries (GB) in BN are investigated. Depending on the tilt angle of grains, GB can be either polar (B-rich or N-rich), constituted by 5|7s, or unpolar, composed of 4|8s. The polar GBs carry net charges, positive at B-rich and negative at N-rich ones. In contrast to GBs in graphene which generally impede the electronic transport, polar GBs have a smaller bandgap compared to perfect BN, which may suggest interesting electronic and optical applications. PMID- 22780218 TI - Spatio-temporal control of neural activity in vivo using fluorescence microendoscopy. AB - Controlling neural activity with high spatio-temporal resolution is desired for studying how neural circuit dynamics control animal behavior. Conventional methods for manipulating neural activity, such as electrical microstimulation or pharmacological blockade, have poor spatial and/or temporal resolution. Algal protein channelrhodopsin-2 (ChR2) enables millisecond-precision control of neural activity. However, a photostimulation method for high spatial resolution mapping in vivo is yet to be established. Here, we report a novel optical/electrical probe, consisting of optical fiber bundles and metal electrodes. Optical fiber bundles were used as a brain-insertable endoscope for image transfer and stimulating light delivery. Light-induced activity from ChR2-expressing neurons was detected with electrodes bundled to the endoscope, enabling verification of light-evoked action potentials. Photostimulation through optical fiber bundles of transgenic mice expressing ChR2 in layer 5 cortical neurons resulted in single whisker movement, indicating spatially restricted activation of neurons in vivo. The probe system described here and a combination of various photoactive molecules will facilitate studies on the causal link between specific neural activity patterns and behavior. PMID- 22780219 TI - Sensitivity and specificity of seizure-onset zone estimation by ictal magnetoencephalography. AB - PURPOSE: Ictal video-electroencephalography (EEG) is commonly used to establish ictal onset-zone location. Recently software development has enabled systematic studies of ictal magnetoencephalography (MEG). In this article, we evaluate the ability of ictal MEG signals to localize the seizure-onset zone. METHODS: Twenty six patients underwent ictal MEG and epilepsy surgery. Prediction of seizure onset zone by ictal and interictal MEG was retrospectively compared with ictal onset area found by intracranial EEG in 12 patients. The specificity and sensitivity of the prediction were calculated at hemisphere-lobe (HL) and at hemisphere-lobe-surface (HLS) levels. KEY FINDINGS: The sensitivity of ictal MEG source localization was 0.958 on HL and 0.706 on HLS levels, and its specificity was 0.900 on HL and 0.731 on HLS levels. The interictal MEG dipole cluster, defined as >10 dipoles on one lobar surface, had sensitivity of 0.400 and specificity of 0.769. Ictal MEG was equally sensitive and specific on dorsolateral and nondorsolateral neocortical surfaces up to a depth of 4 cm from the scalp. SIGNIFICANCE: Sources of ictal-onset MEG signals and interictal dipole clusters are essentially equally specific in estimation of the ictal-onset zone on lobar surface resolution, but ictal MEG is more sensitive. On the lobe resolution, ictal MEG estimates ictal-onset zone with high sensitivity and specificity. PMID- 22780220 TI - Feels like the real thing: imagery is both more realistic and emotional than verbal thought. AB - The production of mental images involves processes that overlap with perception and the extent of this overlap may contribute to reality monitoring errors (i.e., images misremembered as actual events). We hypothesised that mental images would be more confused with having actually seen a pictured object than would alternative representations, such as verbal descriptions. We also investigated whether affective reactions to images were greater than to verbal descriptions, and whether emotionality was associated with more or less reality monitoring confusion. In two experiments signal detection analysis revealed that mental images were more likely to be confused with viewed pictures than were verbal descriptions. There was a general response bias to endorse all emotionally negative items, but accuracy of discrimination between imagery and viewed pictures was not significantly influenced by emotional valence. In a third experiment we found that accuracy of reality monitoring depended on encoding: images were more accurately discriminated from viewed pictures when rated for affect than for size. We conclude that mental images are both more emotionally arousing and more likely to be confused with real events than are verbal descriptions, although source accuracy for images varies according to how they are encoded. PMID- 22780221 TI - Edge-induced active sites enhance the reactivity of large aluminum cluster anions with alcohols. AB - Understanding the emergence of properties from the size-selective cluster regime to larger nanoparticles is one of the principal goals of nanoscience. We have measured the size-selective reactivity of aluminum cluster anions with alcohols. All clusters with more than 20 atoms are found to be reactive, while Al11(-), Al13(-), and Al20(-) show enhanced resistance to oxidation at smaller sizes. The reactivity of aluminum cluster anions with water, methanol, and tert-butyl alcohol all exhibit patterns that require complementary active sites (Lewis acid, Lewis base) on adjacent atoms. Theoretical investigations reveal that at small sizes, the location of reactive pairs occurs on specific active sites, but at larger sizes the reactive pairs begin to accumulate on the edges between facets, marking the transition from the nonscalable size-dependent regime to the scalable regime where the nanoparticles are universally reactive. PMID- 22780222 TI - Highly efficient nanoarchitectured Ni5TiO7 catalyst for biomass gasification. AB - We report the synthesis of needle-shaped nanocrystals of Ni(5)TiO(7) utilizing a solid-phase reaction of NiO with a porous and rough TiO(2) surface produced by plasma electrolytic oxidation. The single crystalline orthorhombic nanocrystals are grown along the [010] axis, featuring a length of ~10 MUm and diameters varying from several tens of nanometers up to 200 nm. The resulted novel Ni(5)TiO(7)/TiO(2)/Ti nanoarchitectured compound composite has been proven outstandingly active as a catalyst and appears most suitable for high-temperature operation in biomass gasification. The findings may pave the way to an improved and environmentally friendly technology of energy generation. PMID- 22780224 TI - Feasibility study on the use of visible-near-infrared spectroscopy for the screening of individual and total glucosinolate contents in broccoli. AB - The potential of visible-near-infrared spectroscopy to determine selected individual and total glucosinolates in broccoli has been evaluated. Modified partial least-squares regression was used to develop quantitative models to predict glucosinolate contents. Both the whole spectrum and different spectral regions were separately evaluated to develop the quantitative models; in all cases the best results were obtained using the near-infrared zone between 2000 and 2498 nm. These models have been externally validated for the screening of glucoraphanin, glucobrassicin, 4-methoxyglucobrassicin, neoglucobrassicin, and total glucosinolates contents. In addition, discriminant partial least-squares was used to distinguish between two possible broccoli cultivars and showed a high degree of accuracy. In the case of the qualitative analysis, best results were obtained using the whole spectrum (i.e., 400-2498 nm) with a correct classification rate of 100% in external validation being obtained. PMID- 22780225 TI - Photochemically grafted polystyrene layer assisting selective Au electrodeposition. AB - We describe the selective electrodeposition of submicrometer gold (Au) patterns achieved by a thin film resist layer of polystyrene (PS) that was exposed to ultraviolet (UV) light on a photoreactive monolayer of a benzophenone-containing alkylthiol formed on a Au-plated substrate and patterned by thermal nanoimprint lithography. The presence of a PS graft layer caused by the benzophenone monolayer photochemistry at an interface between the PS resist layer and photoreactive monolayer played the important role of suppressing the unfavorable growth of tiny Au grains in regions masked with the PS resist layer, resulting in the selective Au electrodeposition in aperture regions of PS resist patterns. The suppressive effect on selective Au electrodeposition depended on the molecular weight of PS used as a resist material. Among unimodal PSs having weight-average molecular weights (M(w)'s) of 2100, 10,900, and 106,000 g mol(-1), the PS of M(w) = 10,900 g mol(-1) functioned most effectively as the resist layer. Au electrodeposition at a low current density allowed the preparation of Au lines having widths of submicrometers and a uniform height independent of line widths in resist aperture regions. Submicrometer bump structures of Au lines could be fabricated on transparent silica substrates by the subsequent wet etching of a Au electrode layer and then a chromium adhesive layer. PMID- 22780223 TI - NrCAM-regulating neural systems and addiction-related behaviors. AB - We have previously shown that a haplotype associated with decreased NrCAM expression in brain is protective against addiction vulnerability for polysubstance abuse in humans and that Nrcam knockout mice do not develop conditioned place preferences for morphine, cocaine or amphetamine. In order to gain insight into NrCAM involvement in addiction vulnerability, which may involve specific neural circuits underlying behavioral characteristics relevant to addiction, we evaluated several behavioral phenotypes in Nrcam knockout mice. Consistent with a potential general reduction in motivational function, Nrcam knockout mice demonstrated less curiosity for novel objects and for an unfamiliar conspecific, showed also less anxiety in the zero maze. Nrcam heterozygote knockout mice reduced alcohol preference and buried fewer marbles in home cage. These observations provide further support for a role of NrCAM in substance abuse including alcoholism vulnerability, possibly through its effects on behavioral traits that may affect addiction vulnerability, including novelty seeking, obsessive compulsion and responses to aversive or anxiety-provoking stimuli. Additionally, in order to prove glutamate homeostasis hypothesis of addiction, we analyzed glutamatergic molecules regulated by NRCAM expression. Glutaminase appears to be involved in NrCAM-related molecular pathway in two different tissues from human and mouse. An inhibitor of the enzyme, prolyl-leucyl glycinamide, treatment produced, at least, some of the phenotypes of mice shown in alcohol preference and in anxiety-like behavior. Thus, NrCAM could affect addiction-related behaviors via at least partially modulation of some glutamatergic pathways and neural function in brain. PMID- 22780226 TI - Life cycle impact assessment of terrestrial acidification: modeling spatially explicit soil sensitivity at the global scale. AB - This paper presents a novel life cycle impact assessment (LCIA) approach to derive spatially explicit soil sensitivity indicators for terrestrial acidification. This global approach is compatible with a subsequent damage assessment, making it possible to consistently link the developed midpoint indicators with a later endpoint assessment along the cause-effect chain-a prerequisite in LCIA. Four different soil chemical indicators were preselected to evaluate sensitivity factors (SFs) for regional receiving environments at the global scale, namely the base cations to aluminum ratio, aluminum to calcium ratio, pH, and aluminum concentration. These chemical indicators were assessed using the PROFILE geochemical steady-state soil model and a global data set of regional soil parameters developed specifically for this study. Results showed that the most sensitive regions (i.e., where SF is maximized) are in Canada, northern Europe, the Amazon, central Africa, and East and Southeast Asia. However, the approach is not bereft of uncertainty. Indeed, a Monte Carlo analysis showed that input parameter variability may induce SF variations of up to over 6 orders of magnitude for certain chemical indicators. These findings improve current practices and enable the development of regional characterization models to assess regional life cycle inventories in a global economy. PMID- 22780227 TI - Dermatofibrosarcoma protuberans in children: an update on the diagnosis and treatment. AB - Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of low grade malignant potential. Although rare, pediatric cases pose a particular challenge in diagnosis and management. In children, the clinical appearance may be heterogeneous and a high index of suspicion is necessary to avoid delays in diagnosis which can lead to further morbidity. Histologic examination, often with the use of appropriate immunostains, is necessary for diagnosis. Advances in the understanding of the molecular genetics of DFSP have led to further diagnostic and therapeutic modalities. DFSP is thought to result from a translocation between platelet-derived growth factor beta (PDGFB, 22q13.1) and type 1 collagen (COL1A1, 17q21~22) leading to a fusion protein (PDGFB) which stimulates the PDGF receptor. Detection of this translocation in tissue via PCR or fluorescence in situ hybridization (FISH) can be helpful in difficult cases. While surgery with wide local excision or Mohs micrographic surgery is the mainstay of treatment, the use of targeted therapy with imatanib mesylate shows promise in large or unresectable tumors. Knowledge of the clinical features, histology, genetics, and treatment options is important for successful management of these tumors. PMID- 22780229 TI - Survival of molar teeth after resective periodontal therapy--a retrospective study. AB - AIM: To study outcomes of molar teeth after resective therapy performed with the intention to prolong the lifespan of teeth having one or more unsaveable roots, and without which tooth extraction would be inevitable. MATERIAL AND METHODS: Clinical records of 149 subjects who had undergone resective therapy were retrieved. Demography and dental history were recorded, and a recall examination was undertaken. Cox regression models were performed. RESULTS: Of the 149 resective therapies, 132 (88.6%) were performed for periodontal reasons. Eighty nine (59.7%) teeth subjected to resective therapies had been extracted by the time of recall (mean 10 years post-resection). The median survival period was 74 months. Factors significantly associated with shorter survival duration of teeth subjected to resective therapy were: age at resective therapy; pre-operative radiographic bone height of the remaining root(s) <50%; pre-treatment mobility II or above and not being splinted to neighbouring teeth nor incorporated as a bridge abutment. CONCLUSION: There was increased risk of tooth loss with increasing age at resection, grade II mobility or above, and reduced pre operative radiographic bone heights around roots to remain. Splinting of a resected tooth to neighbouring teeth appeared to confer a protective effect towards its survival. PMID- 22780230 TI - High-resolution modeling assisted design of customized and individualized transcranial direct current stimulation protocols. AB - OBJECTIVES: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity currents facilitating or inhibiting spontaneous neuronal activity. tDCS is attractive since dose is readily adjustable by simply changing electrode number, position, size, shape, and current. In the recent past, computational models have been developed with increased precision with the goal to help customize tDCS dose. The aim of this review is to discuss the incorporation of high-resolution patient-specific computer modeling to guide and optimize tDCS. METHODS: In this review, we discuss the following topics: 1) The clinical motivation and rationale for models of transcranial stimulation is considered pivotal in order to leverage the flexibility of neuromodulation; 2) the protocols and the workflow for developing high-resolution models; 3) the technical challenges and limitations of interpreting modeling predictions; and 4) real cases merging modeling and clinical data illustrating the impact of computational models on the rational design of rehabilitative electrotherapy. CONCLUSIONS: Though modeling for noninvasive brain stimulation is still in its development phase, it is predicted that with increased validation, dissemination, simplification, and democratization of modeling tools, computational forward models of neuromodulation will become useful tools to guide the optimization of clinical electrotherapy. PMID- 22780299 TI - Association of p53 Arg72Pro polymorphism with gastric cancer: a meta-analysis. AB - BACKGROUND: p53 tumor suppressor gene Arg72Pro polymorphism has been associated with gastric cancer. However, results were inconsistent. We performed this meta analysis to estimate the association between p53 Arg72Pro polymorphism and gastric cancer. METHODS: An electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and the association was assess by pooled odds ratio (ORs) with 95% confidence interval (CIs). RESULTS: The meta-analysis suggested that the p53 Arg72Pro was associated with the gastric cancer risk (Additive model: OR = 1.149, 95% CI = 1.045-1.263, p = 0.004; Dominant model: OR = 1.18, 95% CI = 1.049-1.328, p = 0.006; Recessive model: OR = 1.202, 95% CI = 1.013-1.427, p = 0.035) in Asian subgroup. CONCLUSION: This meta-analysis suggests that p53 Arg72Pro polymorphism is associated with increased risk of gastric cancer in Asians. PMID- 22780231 TI - Cranial muscles in amphibians: development, novelties and the role of cranial neural crest cells. AB - Our research on the evolution of the vertebrate head focuses on understanding the developmental origins of morphological novelties. Using a broad comparative approach in amphibians, and comparisons with the well-studied quail-chicken system, we investigate how evolutionarily conserved or variable different aspects of head development are. Here we review research on the often overlooked development of cranial muscles, and on its dependence on cranial cartilage development. In general, cranial muscle cell migration and the spatiotemporal pattern of cranial muscle formation appears to be very conserved among the few species of vertebrates that have been studied. However, fate-mapping of somites in the Mexican axolotl revealed differences in the specific formation of hypobranchial muscles (tongue muscles) in comparison to the chicken. The proper development of cranial muscles has been shown to be strongly dependent on the mostly neural crest-derived cartilage elements in the larval head of amphibians. For example, a morpholino-based knock-down of the transcription factor FoxN3 in Xenopus laevis has drastic indirect effects on cranial muscle patterning, although the direct function of the gene is mostly connected to neural crest development. Furthermore, extirpation of single migratory streams of cranial neural crest cells in combination with fate-mapping in a frog shows that individual cranial muscles and their neural crest-derived connective tissue attachments originate from the same visceral arch, even when the muscles attach to skeletal components that are derived from a different arch. The same pattern has also been found in the chicken embryo, the only other species that has been thoroughly investigated, and thus might be a conserved pattern in vertebrates that reflects the fundamental nature of a mechanism that keeps the segmental order of the head in place despite drastic changes in adult anatomy. There is a need for detailed comparative fate-mapping of pre-otic paraxial mesoderm in amphibians, to determine developmental causes underlying the complicated changes in cranial muscle development and architecture within amphibians, and in particular how the novel mouth apparatus in frog tadpoles evolved. This will also form a foundation for further research into the molecular mechanisms that regulate rostral head morphogenesis. Our empirical studies are discussed within a theoretical framework concerned with the evolutionary origin and developmental basis of novel anatomical structures in general. We argue that a common developmental origin is not a fool-proof guide to homology, and that a view that sees only structures without homologs as novel is too restricted, because novelties must be produced by changes in the same framework of developmental processes. At the level of developmental processes and mechanisms, novel structures are therefore likely to have homologs, and we need to develop a hierarchical concept of novelty that takes this into account. PMID- 22780300 TI - Establishing faculty needs and priorities for peer-mentoring groups using a nominal group technique. AB - Peer-mentoring groups are purported to enhance faculty productivity and retention, but the literature about implementation is sparse. Nominal Group Sessions (n=5) with 66 faculty members in different tracks developed prioritized lists of unmet professional development needs and potential group activities. Common items included mentor relationships, research skills, informal peer discussions of successes and challenges, and professional skills workshops. Items particular to specific academic tracks included integration of non-clinical faculty, and gaining recognition in non-research tracks. PMID- 22780301 TI - Effect of loading rate on mechanical properties and fracture morphology of spider silk. AB - Spider silks have been shown to have impressive mechanical properties. In order to assess the effect of extension rate, both quasi-static and high-rate tensile properties were determined for single fibers of major (MA) and minor (MI) ampullate single silk from the orb weaving spider Nephila clavipes . Low rate tests have been performed using a DMA Q800 at 10(-3) s(-1), while high rate analysis was done at 1700 s(-1) utilizing a miniature Kolsky bar apparatus. Rate effects exhibited by both respective silk types are addressed, and direct comparison of the tensile response between the two fibers is made. The fibers showed major increases in toughness at the high extension rate. Mechanical properties of these organic silks are contrasted to currently employed ballistic fibers and examination of fiber fracture mechanisms are probed via scanning electron microscope, revealing a globular rupture surface topography for both rate extremums. PMID- 22780302 TI - Chemical composition and antimicrobial activity of the leaf essential oil of Skimmia laureola growing wild in Jammu and Kashmir, India. AB - The analysis of Skimmia laureola hydrodistillate by gas chromatography coupled with mass spectrometry revealed the presence of 20 constituents, representing 94.6% of the total oil. The major constituents of oil were linalyl acetate (33.0%), linalool (25.0%), limonene (8.1%), alpha-terpineol (5.9%) and geranyl acetate (5.9%). The monoterpene (93.4%) rich essential oil was evaluated for its antibacterial and antifungal activities against seven microorganisms by agar diffusion and microdilution methods. The oil showed appreciable antimicrobial effects against all Gram-positive bacteria tested, including methicillin resistant Staphylococcus aureus and Staphylococcus epidermidis with MIC values 32 and 64 ug mL(-1), respectively. The oil also exhibited strong fungicidal activity against Aspergillus niger and Penicillium chrysogenum with MIC value in the range 32-16 ug mL(-1). The oil could be used in the formulation of antimicrobial agents. PMID- 22780304 TI - Modeling the transport of nanoparticle-filled binary fluids through micropores. AB - Understanding the transport of multicomponent fluids through porous medium is of great importance for a number of technological applications, ranging from ink jet printing and the production of textiles to enhanced oil recovery. The process of capillary filling is relatively well understood for a single-component fluid; much less attention, however, has been devoted to investigating capillary filling processes that involve multiphase fluids, and especially nanoparticle-filled fluids. Here, we examine the behavior of binary fluids containing nanoparticles that are driven by capillary forces to fill well-defined pores or microchannels. To carry out these studies, we use a hybrid computational approach that combines the lattice Boltzmann model for binary fluids with a Brownian dynamics model for the nanoparticles. This hybrid approach allows us to capture the interactions among the fluids, nanoparticles, and pore walls. We show that the nanoparticles can dynamically alter the interfacial tension between the two fluids and the contact angle at the pore walls; this, in turn, strongly affects the dynamics of the capillary filling. We demonstrate that by tailoring the wetting properties of the nanoparticles, one can effectively control the filling velocities. Our findings provide fundamental insights into the dynamics of this complex multicomponent system, as well as potential guidelines for a number of technological processes that involve capillary filling with nanoparticles in porous media. PMID- 22780303 TI - Pd(II)-catalyzed ortho trifluoromethylation of arenes and insights into the coordination mode of acidic amide directing groups. AB - A Pd(II)-catalyzed trifluoromethylation of ortho C-H bonds with an array of N arylbenzamides derived from benzoic acids is reported. N-Methylformamide has been identified as a crucial promoter of C-CF(3) bond formation from the Pd center. X ray characterization of the C-H insertion intermediate has revealed a rare coordination mode of acidic amides as directing groups and the origin of their capacity in directing C-H activation. PMID- 22780305 TI - Epitaxial graphene nanoribbon array fabrication using BCP-assisted nanolithography. AB - A process for fabricating dense graphene nanoribbon arrays using self-assembled patterns of block copolymers on graphene grown epitaxially on SiC on the wafer scale has been developed. Etching masks comprising long and straight nanoribbon array structures with linewidths as narrow as 10 nm were fabricated, and the patterns were transferred to graphene. Our process combines both top-down and self-assembly steps to fabricate long graphene nanoribbon arrays with low defect counts. These are the narrowest nanoribbon arrays of epitaxial graphene on SiC fabricated to date. PMID- 22780306 TI - Mapping an X-linked locus that influences heat-induced febrile seizures in mice. AB - PURPOSE: Febrile seizures (FS) are the most common seizure type in children between the age of 6 months and 5 years. Although FS are largely benign, recurrent FS are a major risk factor for developing temporal lobe epilepsy (TLE) later in life. The mechanisms underlying FS are largely unknown; however, family and twin studies indicate that FS susceptibility is under complex genetic control. We have recently developed a phenotypic screen to study the genetics of FS susceptibility in mice. Using this screen in a phenotype-driven genetic strategy we analyzed the C57BL/6J-Chr #(A)/NaJ chromosome substitution strain (CSS) panel. In each CSS line one chromosome of the A/J strain is substituted in a genetically homogeneous C57BL/6J background. The analysis of the CSS panel revealed that A/J chromosomes 1, 2, 6, 10, 13, and X carry at least one quantitative trait locus (QTL) for heat-induced FS susceptibility. The fact that many X-linked genes are highly expressed in the brain and have been implicated in human developmental disorders often presenting with seizures (like fragile X mental retardation) prompted us to map the chromosome X QTL. METHODS: C57BL/6J mice were mated with C57BL/6J-Chr X(A) /NaJ (CSSX) to generate F(2)-generations CXBL6 and BL6CX-originating from CSSX or C57BL/6J mothers, respectively. Heat induced FS were elicited on postnatal day 14 by exposure to a controlled warm airstream of 50 degrees C. The latency to heat-induced FS is our phenotype. This phenotype has previously been validated by video-electroencephalography (EEG) monitoring. After phenotyping and genotyping the F(2)-population, QTL analysis was performed using R/QTL software. KEY FINDINGS: QTL analysis revealed a significant peak with an LOD-score of 3.25. The 1-LOD confidence interval (149,886,866-158,836,462 bp) comprises 52 protein coding genes, of which 34 are known to be brain expressed. Two of these brain-expressed genes have previously been linked to X-linked epilepsies, namely Cdkl5 and Pdha1. SIGNIFICANCE: Our results show that the mouse genetics of X-linked FS susceptibility is complex, and that our heat-induced FS-driven genetic approach is a powerful tool for use in unraveling the complexities of this trait in mice. Fine-mapping and functional studies will be required to further identify the X-linked FS susceptibility genes. PMID- 22780307 TI - Design of a novel Cu2O/TiO2/carbon aerogel electrode and its efficient electrosorption-assisted visible light photocatalytic degradation of 2,4,6 trichlorophenol. AB - Cu(2)O/TiO(2) heterojunction photocatalyst is built on carbon aerogel (CA) substrate with good adsorption properties by sol impregnation and seed-mediated synthesis approach. The Cu(2)O/TiO(2)/CA electrode has excellent electrosorptive and high efficient photocatalytic properties. Its morphology and surface chemical composition are characterized with SEM, TEM, X-ray diffraction (XRD) and Raman spectra. The UV-vis diffuse reflectance spectra show that the optical absorption edge for Cu(2)O/TiO(2)/CA appears at 636 nm. Under visible-light (lambda > 420 nm) irradiation, the photocurrent density increment on Cu(2)O/TiO(2)/CA is 60 times of that on Cu(2)O/TiO(2)/FTO. The electrochemical characteristic is investigated with electrochemical impedance spectrum (EIS). The Cu(2)O/TiO(2)/CA electrode is further applied in the electrosorptive photodegradation of the 2,4,6 trichlorophenol (2,4,6-TCP) wastewater. The result shows that the removal ratio of 2,4,6-TCP in 5.5 h on Cu(2)O/TiO(2)/CA is 96.3% and the TOC removal is 91.3%. The intermediates generated in the degradation process are analyzed by GC-MS and HPLC. The possible mechanism of visible light photocatalytic degradation of 2,4,6 TCP on Cu(2)O/TiO(2)/CA is also studied. PMID- 22780308 TI - The usefulness of lean six sigma to the development of a clinical pathway for hip fractures. AB - AIMS AND OBJECTIVES: The objective of this study was to show the usefulness of lean six sigma (LSS) for the development of a multidisciplinary clinical pathway. METHODS: A single centre, both retrospective and prospective, non-randomized controlled study design was used to identify the variables of a prolonged length of stay (LOS) for hip fractures in the elderly and to measure the effect of the process improvements--with the aim of improving efficiency of care and reducing the LOS. RESULTS: The project identified several variables influencing LOS, and interventions were designed to improve the process of care. Significant results were achieved by reducing both the average LOS by 4.2 days (-31%) and the average duration of surgery by 57 minutes (-36%). The average LOS of patients discharged to a nursing home reduced by 4.4 days. CONCLUSION: The findings of this study show a successful application of LSS methodology within the development of a clinical pathway. Further research is needed to explore the effect of the use of LSS methodology at clinical outcome and quality of life. PMID- 22780309 TI - Methods in 2012, part 2. PMID- 22780312 TI - Profile of Adam Cohen. Revealing potential. Interview by Kristie Nybo. PMID- 22780314 TI - The new molecular gastronomy, or, a gustatory tour of network analysis. PMID- 22780315 TI - Molecular biology techniques Q&A. Western blot: protein migration. PMID- 22780316 TI - The rise of high throughput. AB - The realization that gene, protein, and metabolite space is vast has led to the development of novel high-throughput methodologies aimed directly at interrogating biomolecules and their interactions at previously impossible depths. In this special focus section, the editors of BioTechniques explore the development of high-throughput applications in five areas of life science (page 27), while a primary research article by Kapetis et al. details an enhanced software platform capable of automated cross-platform microarray data analysis (page 33). It is our hope that through the articles in this section, readers will obtain a deeper understanding of high-throughput methodologies and their evolution. PMID- 22780317 TI - Tales on the road to high-throughput. PMID- 22780318 TI - High-resolution three-dimensional reconstruction of a whole yeast cell using focused-ion beam scanning electron microscopy. AB - We developed an approach for focused gallium-ion beam scanning electron microscopy with energy filtered detection of backscattered electrons to create near isometric voxels for high-resolution whole cell visualization. Specifically, this method allowed us to create three-dimensional volumes of high-pressure frozen, freeze-substituted Saccharomyces cerevisiae yeast cells with pixel resolutions down to 3 nm/pixel in x, y, and z, supported by both empirical data and Monte Carlo simulations. As a result, we were able to segment and quantify data sets of numerous targeted subcellular structures/organelles at high resolution, including the volume, volume percentage, and surface area of the endoplasmic reticulum, cell wall, vacuoles, and mitochondria from an entire cell. Sites of mitochondrial and endoplasmic reticulum interconnectivity were readily identified in rendered data sets. The ability to visualize, segment, and quantify entire eukaryotic cells at high-resolution (potentially sub-5 nanometers isotropic voxels) will provide new perspectives and insights of the inner workings of cells. PMID- 22780319 TI - Separation of plasmid DNA isoforms using centrifugal ultrafiltration. AB - Centrifugal ultrafiltration is a well-established method for concentrating and purifying DNA. Here, we describe the use of centrifugal ultrafiltration for the separation of plasmid DNA isoforms based on differences in elongational flexibility of the supercoiled, open-circular, and linear plasmids. Transmission of each isoform is minimal below a critical value of the filtration velocity, which is directly related to the magnitude of the centrifugal speed and the system geometry. A discontinuous diafiltration process was used to enrich the desired isoform, as determined by agarose gel electrophoresis. The simplicity and efficacy of this membrane-based separation are attractive for multiple applications requiring the use of separated DNA isoforms. PMID- 22780320 TI - Effective flow cytometric phenotyping of cells using minimal amounts of antibody. AB - Here we introduce a modified antibody staining method that uses up to 80% less antibody for flow cytometry. We demonstrate this method for the detection of antigens expressed at high, moderate, or low levels in mouse and rat lymphocytes as well as mouse mammary epithelial cells. We obtained reproducibly accurate results for the detection of up to seven parameters for activation induced proliferation, cell cycle analysis, and phenotyping of cell-surface and intracellular antigens. PMID- 22780321 TI - Improving genome assemblies by sequencing PCR products with PacBio. AB - Advances in sequencing technologies have dramatically reduced costs in producing high-quality draft genomes. However, there are still many contigs and possible misassembled regions in those draft genomes. Improving the quality of these genomes requires an efficient and economical means to close gaps and resequence some regions. Sequencing pooled gap region PCR products with Pacific Biosciences (PacBio) provides a significantly less expensive means for this need. We have developed a genome improvement pipeline with this strategy after decreasing a loading bias against larger PCR products in the PacBio process. Compared with Sanger technology, this approach is not only cost-effective but also can close gaps greater than 2.5 kb in a single round of reactions, and sequence through high GC regions as well as difficult secondary structures such as small hairpin loops. PMID- 22780323 TI - Effects of self-efficacy on oral health behaviours and gingival health in university students aged 18- or 19-years-old. AB - AIM: Although self-efficacy is known to affect various health-related practises, few studies have clearly examined how self-efficacy correlates with oral health behaviors or the oral health condition. We examined the relationship between gingivitis, oral health behaviors and self-efficacy in university students. MATERIAL & METHODS: A total of 2,111 students (1,197 males, 914 females) aged 18 and 19 years were examined. The degree of gingivitis was expressed as the percentage of bleeding on probing (%BOP). Additional information was collected via a questionnaire regarding oral health behaviors (daily frequency of tooth brushing, use of dental floss and regular check-up). Self-efficacy was assessed using the Self-Efficacy Scale for Self-care (SESS). Path analysis was used to test pathways from self-efficacy to oral health behaviors and %BOP. RESULTS: In the final structural model, self-efficacies were related to each other, and they affected oral health behaviors. Good oral health behaviors reduced dental plaque and calculus, and lower levels of dental plaque and calculus resulted in lower %BOP. CONCLUSION: Higher self-efficacy correlated with better oral health behaviours and gingival health in university students. Improving self-efficacy may be beneficial for maintaining good gingival health in university students. To prevent gingivitis, the approach of enhancing self-efficacy in university students would be useful. PMID- 22780324 TI - A social vaccine? Social and structural contexts of HIV vaccine acceptability among most-at-risk populations in Thailand. AB - A safe and efficacious preventive HIV vaccine would be a tremendous asset for low and middle-income country (LMIC) settings, which bear the greatest global impact of AIDS. Nevertheless, substantial gaps between clinical trial efficacy and real world effectiveness of already licensed vaccines demonstrate that availability does not guarantee uptake. In order to advance an implementation science of HIV vaccines centred on LMIC settings, we explored sociocultural and structural contexts of HIV vaccine acceptability among most-at-risk populations in Thailand, the site of the largest HIV vaccine trial ever conducted. Cross-cutting challenges for HIV vaccine uptake - social stigma, discrimination in healthcare settings and out-of-pocket vaccine cost - emerged in addition to population specific barriers and opportunities. A 'social vaccine' describes broad sociocultural and structural interventions - culturally relevant vaccine promotion galvanised by communitarian norms, mitigating anti-gay, anti-injecting drug user and HIV-related stigma, combating discrimination in healthcare, decriminalising adult sex work and injecting drug use and providing vaccine cost subsidies - that create an enabling environment for HIV vaccine uptake among most at-risk populations. By approaching culturally relevant social and structural interventions as integral mechanisms to the success of new HIV prevention technologies, biomedical advances may be leveraged in renewed opportunities to promote and optimise combination prevention. PMID- 22780325 TI - GABA mediates the network activity-dependent facilitation of axonal outgrowth from the newborn granule cells in the early postnatal rat hippocampus. AB - Neural network activity regulates the development of hippocampal newborn granule cells (GCs). Excitatory GABAergic input is known to be a key player in this regulation. Although calcium signaling is thought to be a downstream mediator of GABA, GABA-induced calcium signaling in newborn GCs is not well understood. We investigated Ca(2+) signaling and its regulatory role in axon and dendrite outgrowth in newborn GCs identified in the organotypic slice culture of early postnatal rat hippocampus. Here, we report that hippocampal network activity can induce calcium transients (CaTs) in newborn GCs during the first post-mitotic week via GABAergic inputs. The GABA-induced CaTs were mediated mainly by L-type Ca(2+) channels. Furthermore, we found that inhibiting any step in the signaling pathway, network activity -> GABA -> L-type Ca(2+) channels, selectively suppressed the axonal outgrowth and pruning of newborn GCs, but not dendritic outgrowth. The GABA(A) receptor blocker bicuculline significantly suppressed axonal outgrowth, despite increasing network activity, thus indicating an essential role of GABAergic inputs. Therefore, we conclude that network activity dependent GABAergic inputs open L-type Ca(2+) channels and promote axonal outgrowth in newborn GC during the first post-mitotic week. PMID- 22780326 TI - Coherent microscopic picture for urea-induced denaturation of proteins. AB - In a previous study, we explored the mechanism of urea-induced denaturation of proteins by performing molecular dynamics (MD) simulations of hen lysozyme in 8 M urea and supported the "direct interaction mechanism" whereby urea denatures protein via dispersion interaction (Hua, L.; Zhou, R. H.; Thirumalai, D.; Berne, B. J. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 16928). Here we perform large scale MD simulations of five representative protein/peptide systems in aqueous urea to investigate if the above mechanism is common to other proteins. In all cases, accumulations of urea around proteins/peptide are observed, suggesting that urea denatures proteins by directly attacking protein backbones and side chains rather than indirectly disrupting water structure as a "water breaker". Consistent with our previous case study of lysozyme, the current energetic analyses with five protein/peptide systems reveal that urea's preferential binding to proteins mainly comes from urea's stronger dispersion interactions with proteins than with bulk solution, whereas the electrostatic (hydrogen bonded) interactions only play a relatively minor (even negative) role during this denaturation process. Furthermore, the simulations of the peptide system at different urea concentrations (8 and 4.5 M), and with different force fields (CHARMM and OPLSAA) suggest that the above mechanism is robust, independent of the urea concentration and force field used. Last, we emphasize the importance of periodic boundary conditions in pairwise energetic analyses. This article provides a comprehensive study on the physical mechanism of urea-induced protein denaturation and suggests that the "dispersion-interaction-driven" mechanism should be general. PMID- 22780327 TI - Self-discrepancy and reduced autobiographical memory specificity in ruminating students and depressed patients. AB - This work uses self-discrepancies as a unifying framework to understand the relationship between autobiographical memory specificity (AMS) and components of rumination (reflection and brooding). Rumination can be triggered by the awareness of a discrepancy between one's current state of being and one's desired state of being. Such discrepancies may partly underlie the phenomenon of reduced AMS (a.k.a. overgeneral memory), which is a phenomenon of great clinical importance especially for depression. The aim of the present studies was to experimentally investigate the impact of a self-discrepancy manipulation on AMS in a student sample (Study 1) and in a depressed sample (Study 2). Results failed to reveal a direct effect of a self-discrepancy manipulation on AMS, but in both studies, actual-ideal discrepancies interacted with the reflection component of rumination with respect to memory specificity. In the self-discrepancy condition, there was a negative association between reflection and change in AMS: Higher reflection was associated with a greater decrease in AMS from pre- to post testing. The results of these two studies suggest that the interplay between components of rumination and self-discrepancy has an effect on memory specificity. PMID- 22780328 TI - Second generation CB1 receptor blockers and other inhibitors of peripheral endocannabinoid overactivity and the rationale of their use against metabolic disorders. AB - INTRODUCTION: Excessive abdominal obesity along with other risk factors results in the metabolic syndrome, which can lead to heart disease, Type-2 diabetes, and death. The endocannabinoid system (ECS) is composed of neutral lipids which signal through the G-protein coupled cannabinoid receptors CB1 and CB2. In abdominal obesity, the ECS is generally up-regulated in central and peripheral tissues and its blockade results in positive metabolic changes. Rimonabant (SR141716) was the first selective CB1 inverse agonist/antagonist marketed for the treatment of obesity; however, psychiatric side effects, which may result from its actions in the brain or its inverse agonism, resulted in its removal from the market. Recently, key metabolic-modulatory roles for the ECS within peripheral tissues have come to light. Thus there has been significant effort put forth by several laboratories to develop either neutral or peripherally restricted CB1 antagonists. AREAS COVERED: In this review we shall provide an overview of the roles the ECS plays outside the brain in regulating metabolism, and highlight the latest advances in the development of neutral and/or peripherally restricted CB1 antagonists, and other state of the art strategies that minimize endocannabinoid overactivity. EXPERT OPINION: The CB1 receptor is potentially a clinically relevant target for the design of therapies against metabolic syndrome, deserving the development and clinical testing of CB1-neutral antagonists which can pass the blood - brain barrier or of peripherally restricted inverse agonists/neutral antagonists. Furthermore, reducing endocannabinoid biosynthesis could represent an alternative strategy to counteract peripheral endocannabinoid overactivity through dietary n-3 polyunsaturated fatty acids or the development of diacylglycerol lipase inhibitors. PMID- 22780330 TI - Financial stress is associated with reduced treatment adherence in HIV-infected adults in a resource-rich setting. AB - OBJECTIVES: Financial stress has been identified as a barrier to antiretroviral adherence, but only in resource- limited settings. Almost half of HIV-infected Australian adults earn no regular income and, despite highly subsidised antiretroviral therapy and universal health care, 3% of HIV-infected Australians cease antiretroviral therapy each year. We studied the relationship between financial stress and treatment adherence in a resource-rich setting. METHODS: Out patients attending the HIV clinic at St Vincent's Hospital between November 2010 and May 2011 were invited to complete an anonymous survey including questions relating to costs and adherence. RESULTS: Of 335 HIV-infected patients (95.8% male; mean age 52 years; hepatitis coinfection 9.2%), 65 patients (19.6%) stated that it was difficult or very difficult to meet pharmacy dispensing costs, 49 (14.6%) reported that they had delayed purchasing medication because of pharmacy costs, and 30 (9.0%) reported that they had ceased medication because of pharmacy costs. Of the 65 patients with difficulties meeting pharmacy costs, 19 (29.2%) had ceased medication vs. 11 (4.1%) of the remaining 270 patients (P < 0.0001). In addition, 19 patients (5.7%) also stated that it was difficult or very difficult to meet travel costs to the clinic. Treatment cessation and interruption were both independently associated with difficulty meeting both pharmacy and clinic travel costs. Only 4.9% had been asked if they were having difficulty paying for medication. CONCLUSIONS: These are the first data to show that pharmacy dispensing and clinic travel costs may affect treatment adherence in a resource-rich setting. Patients should be asked if financial stress is limiting their treatment adherence. PMID- 22780331 TI - Influence of anionic cosolutes and pH on nanoscale zerovalent iron longevity: time scales and mechanisms of reactivity loss toward 1,1,1,2-tetrachloroethane and Cr(VI). AB - Nanoscale zerovalent iron (NZVI) was aged over 30 days in suspension (2 g/L) with different anions (chloride, perchlorate, sulfate, carbonate, nitrate), anion concentrations (5, 25, 100 mN), and pH (7, 8). During aging, suspension samples were reacted periodically with 1,1,1,2-tetrachloroethane (1,1,1,2-TeCA) and Cr(VI) to determine the time scales and primary mode of NZVI reactivity loss. Rate constants for 1,1,1,2-TeCA reduction in Cl(-), SO(4)(2-), and ClO(4)(-) suspensions decreased by 95% over 1 month but were generally equivalent to one another, invariant of concentration and independent of pH. In contrast, longevity toward 1,1,1,2-TeCA depended upon NO(3)(-) and HCO(3)(-) concentration, with complete reactivity loss over 1 and 14 days, respectively, in 25 mN suspensions. X-ray diffraction suggests that reactivity loss toward 1,1,1,2-TeCA in most systems results from Fe(0) conversion into magnetite, whereas iron carbonate hydroxide formation limits reactivity in HCO(3)(-) suspensions. Markedly different trends in Cr(VI) removal capacity (mg Cr/g NZVI) were observed during aging, typically exhibiting greater longevity and a pronounced pH-dependence. Notably, a strong linear correlation exists between Cr(VI) removal capacities and rates of Fe(II) production measured in the absence of Cr(VI). While Fe(0) availability dictates longevity toward 1,1,1,2-TeCA, this correlation suggests surface-associated Fe(II) species are primarily responsible for Cr(VI) reduction. PMID- 22780329 TI - Translational neuromodulation: approximating human transcranial magnetic stimulation protocols in rats. AB - OBJECTIVE: Transcranial magnetic stimulation (TMS) is a well-established clinical protocol with numerous potential therapeutic and diagnostic applications. Yet, much work remains in the elucidation of TMS mechanisms, optimization of protocols, and in development of novel therapeutic applications. As with many technologies, the key to these issues lies in the proper experimentation and translation of TMS methods to animal models, among which rat models have proven popular. A significant increase in the number of rat TMS publications has necessitated analysis of their relevance to human work. We therefore review the essential principles for the approximation of human TMS protocols in rats as well as specific methods that addressed these issues in published studies. MATERIALS AND METHODS: We performed an English language literature search combined with our own experience and data. We address issues that we see as important in the translation of human TMS methods to rat models and provide a summary of key accomplishments in these areas. RESULTS: An extensive literature review illustrated the growth of rodent TMS studies in recent years. Current advances in the translation of single, paired-pulse, and repetitive stimulation paradigms to rodent models are presented. The importance of TMS in the generation of data for preclinical trials is also highlighted. CONCLUSIONS: Rat TMS has several limitations when considering parallels between animal and human stimulation. However, it has proven to be a useful tool in the field of translational brain stimulation and will likely continue to aid in the design and implementation of stimulation protocols for therapeutic and diagnostic applications. PMID- 22780332 TI - The perception and identification of facial emotions in individuals with autism spectrum disorders using the Let's Face It! Emotion Skills Battery. AB - BACKGROUND: Although impaired social-emotional ability is a hallmark of autism spectrum disorder (ASD), the perceptual skills and mediating strategies contributing to the social deficits of autism are not well understood. A perceptual skill that is fundamental to effective social communication is the ability to accurately perceive and interpret facial emotions. To evaluate the expression processing of participants with ASD, we designed the Let's Face It! Emotion Skills Battery (LFI! Battery), a computer-based assessment composed of three subscales measuring verbal and perceptual skills implicated in the recognition of facial emotions. METHODS: We administered the LFI! Battery to groups of participants with ASD and typically developing control (TDC) participants that were matched for age and IQ. RESULTS: On the Name Game labeling task, participants with ASD (N = 68) performed on par with TDC individuals (N = 66) in their ability to name the facial emotions of happy, sad, disgust and surprise and were only impaired in their ability to identify the angry expression. On the Matchmaker Expression task that measures the recognition of facial emotions across different facial identities, the ASD participants (N = 66) performed reliably worse than TDC participants (N = 67) on the emotions of happy, sad, disgust, frighten and angry. In the Parts-Wholes test of perceptual strategies of expression, the TDC participants (N = 67) displayed more holistic encoding for the eyes than the mouths in expressive faces whereas ASD participants (N = 66) exhibited the reverse pattern of holistic recognition for the mouth and analytic recognition of the eyes. CONCLUSION: In summary, findings from the LFI! Battery show that participants with ASD were able to label the basic facial emotions (with the exception of angry expression) on par with age- and IQ-matched TDC participants. However, participants with ASD were impaired in their ability to generalize facial emotions across different identities and showed a tendency to recognize the mouth feature holistically and the eyes as isolated parts. PMID- 22780333 TI - Even without additional therapy, serum thyroglobulin concentrations often decline for years after total thyroidectomy and radioactive remnant ablation in patients with differentiated thyroid cancer. AB - BACKGROUND: Current management guidelines suggest that 6-12 months after total thyroidectomy and radioactive iodine remnant ablation (RAI-RA), patients with differentiated thyroid cancer should be re-evaluated with serum thyroglobulin (Tg) and neck ultrasonography to assess the efficacy of initial treatment and to guide subsequent management. However, if serum Tg levels can continue to decline for many years after RAI-RA, then an early assessment of response to therapy could lead to excessive evaluations and treatments in patients with low-level Tg values that are likely to resolve over time without additional therapies. METHODS: Serum Tg concentrations in patients with differentiated thyroid cancer, who had been thyroidectomized (Tx), received RAI-RA, and who were receiving levothyroxine to suppress serum thyrotropin (suppressed serum Tg), were retrospectively analyzed. The study included 299 patients, 69% of whom were women with an overall median age of 46 years and who had a median follow-up of 7 years. The study was limited to patients who received no additional treatments beyond total Tx, RAI-RA, and levothyroxine therapy to suppress thyrotropin. The primary endpoints were the time required to achieve the lowest Tg (nadir Tg) and the time required to achieve a suppressed serum Tg<1 ng/mL. RESULTS: The nadir -suppressed serum Tg was achieved by 6 months in 58% of the patients and by 12 months in 75% of the patients. The remaining 25% of patients required 18 months or longer to reach the nadir Tg. However, in the subgroup of patients that eventually reached a nadir suppressed serum Tg<1 ng/mL (n=223 patients), this goal was achieved by 6 months in 81%, by no more than 12 months in 91%, and by no more than 18 months in 94%. In patients with a 6-month suppressed serum Tg of 1-5 ng/mL, 54% eventually developed a suppressed serum Tg of <1 ng/mL without additional therapy. CONCLUSIONS: In patients selected for continued observation, serum Tg levels often continue to decline for several years after total Tx and RAI-RA. While a 6 12-month assessment of the response to initial therapy is useful in patient management, strong consideration should be given to continued observation without additional therapy in patients with well-differentiated thyroid cancer who have 6 month suppressed serum Tg values of 1-5 ng/mL without a structurally identifiable disease. PMID- 22780334 TI - Degradation of silver-polysaccharide nanocomposite in solution and as coating on fiber-reinforced composites by lysozyme and hydrogen peroxide. PMID- 22780335 TI - Divergent construction of nitrogen-containing polycyclic compounds with a dearomatization strategy. AB - The oxidative dearomatization of para-substituted o-alkynylanilines afforded 2 alkynyl cyclohexadienimines, which can act as active substrates for reaction with electron-rich styrenes. The reaction is metal-controlled. Bi(OTf)3-catalyzed reactions afforded 3,4-dihydro-cyclopenta[c,d]indoles, and AgOTf-catalyzed reactions provided tricyclic pyrrole derivatives. PMID- 22780425 TI - Short-term intravenous insulin infusion is associated with reduced expression of NADPH oxidase p47(phox) subunit in monocytes from type 2 diabetes patients. AB - Hyperglycemia is a well-known inducing factor of oxidative stress through activation of NADPH oxidase. In addition to its plasma glucose lowering effect, insulin may also have antioxidant activity and was shown to downregulate NADPH oxidase expression in vitro. In this study, we show that a short-term (3-day) intravenous insulin infusion in patients with type 2 diabetes induces normalization of both glycemia and mRNA expression of circulating monocyte p47(phox) subunit. PMID- 22780426 TI - New long-chain aliphatic compounds from Peperomia dindygulensis. AB - Three long-chain aliphatic compounds, including one new polyketide derivative, dindygulerione C (1), one new octaketide derivative, dindygulerione D (2) and one new acylresorcinol derivative dindyguleranone (3) were isolated from the whole plant of the Chinese anticancer folk medicine Peperomia dindygulensis Miq. (Piperaceae). Dindygulerione C is an unprecedented example of a N-containing polyketide. The chemical structures and configurations of 1-3 were elucidated as (-)-(4S)-2-[(Z)-1'-(6",7"-dihydroxyphenethyl-amino)octadec-11'-enylidene]-4 hydroxycyclohexane-1,3-dione (1), (+)-2-heptadecyl-4-hydroxy-3,4,7,8-tetrahydro 2H-chromen-5(6H)-one (2) and 2-(1,3-dihydroxyphenyl)-octacosan-1'-one (3), respectively, by comparing with the literature data and extensive spectroscopic methods, including 2-D NMR and circular dichroism spectroscopic analysis. The cytotoxicity of 1-3 was evaluated against Hep3B and HepG2 liver cancer cell lines. PMID- 22780427 TI - Unique ring families: a chemically meaningful description of molecular ring topologies. AB - The perception of a set of rings forms the basis for a number of chemoinformatics applications, e.g. the systematic naming of compounds, the calculation of molecular descriptors, the matching of SMARTS expressions, and the generation of atomic coordinates. We introduce the concept of unique ring families (URFs) as an extension of the concept of relevant cycles (RCs). URFs are consistent for different atom orders and represent an intuitive description of the rings of a molecular graph. Furthermore, in contrast to RCs, URFs are polynomial in number. We provide an algorithm to efficiently calculate URFs in polynomial time and demonstrate their suitability for real-time applications by providing computing time benchmarks for the PubChem Database. URFs combine three important properties of chemical ring descriptions, for the first time, namely being unique, chemically meaningful, and efficient to compute. Therefore, URFs are a valuable alternative to the commonly used concept of the smallest set of smallest rings (SSSR) and would be suited to become the standard measure for ring topologies of small molecules. PMID- 22780428 TI - First-principles study of the role of interconversion between NO2, N2O4, cis-ONO NO2, and trans-ONO-NO2 in chemical processes. AB - Experimental results, such as NO2 hydrolysis and the hypergolicity of hydrazine/nitrogen tetroxide pair, have been interpreted in terms of NO2 dimers. Such interpretations are complicated by the possibility of several forms for the dimer: symmetric N2O4, cis-ONO-NO2, and trans-ONO-NO2. Quantum mechanical (QM) studies of these systems are complicated by the large resonance energy in NO2 which changes differently for each dimer and changes dramatically as bonds are formed and broken. As a result, none of the standard methods for QM are uniformly reliable. We report here studies of these systems using density functional theory (B3LYP) and several ab initio methods (MP2, CCSD(T), and GVB-RCI). At RCCSD(T)/CBS level, the enthalpic barrier to form cis-ONO-NO2 is 1.9 kcal/mol, whereas the enthalpic barrier to form trans-ONO-NO2 is 13.2 kcal/mol, in agreement with the GVB-RCI result. However, to form symmetric N2O4, RCCSD(T) gives an unphysical barrier due to the wrong asymptotic behavior of its reference function at the dissociation limit, whereas GVB-RCI shows no barrier for such a recombination. The difference of barrier heights in these three recombination reactions can be rationalized in terms of the amount of B2 excitation involved in the bond formation process. We find that the enthalpic barrier for N2O4 isomerizing to trans-ONO-NO2 is 43.9 kcal/mol, ruling out the possibility of such an isomerization playing a significant role in gas-phase hydrolysis of NO2. A much more favored path is to form cis-ONO-NO2 first then convert to trans-ONO-NO2 with a 2.4 kcal/mol enthalpic barrier. We also propose that the isotopic oxygen exchange in NO2 gas is possibly via the formation of trans-ONO-NO2 followed by ON(+) migration. PMID- 22780429 TI - The development of growth references and growth charts. AB - CONTEXT: De Montbeillard produced the first growth chart in the late 18(th) century. Since then, growth assessment has developed to become an essential component of child health practice. OBJECTIVE: To provide a brief history of (i) anthropometry, i.e. growth measurements; (ii) growth references, the statistical summary of anthropometry and (iii) growth charts, the visual representation of growth references for clinical use. METHODS: The major contributors in the three categories over the past 200 years were identified and their historical contributions put in context with more recent developments. RESULTS: Anthropometry was originally collected for administrative or public health purposes, its medical role emerging at the end of the 19(th) century. Growth reference data were collected in earnest from the 19(th) century, during which time the familiar statistical summary statistics-mean, SD, centiles-were developed. More advanced statistical methods emerged much later. Growth charts first appeared in the late 19(th) century and Tanner and Whitehouse later popularized the concepts of velocity and conditional references for growth in puberty. An important recent reference is the WHO growth standard, which documents optimal growth and has been adopted by many countries including the UK. Arising from it, the UK-WHO charts have pioneered many design features to improve usability and accuracy. CONCLUSION: Growth charts have developed considerably in 200 years and they represent an impressive synthesis of anthropometry, statistical summary and chart design. PMID- 22780430 TI - Highly enantioselective proton-initiated polycyclization of polyenes. AB - This report describes the synthesis of a range of chiral polycyclic molecules (tricyclic to pentacyclic) from achiral polyene precursors by enantioselective proton-initiated polycyclization promoted by the 1:1 complex of o,o'-dichloro BINOL and SbCl(5). Excellent yields (ca. 90% per ring formed) and enantioselectivety (20:1 to 50:1) were obtained. The process is practical as well as efficient, because the chiral ligand is both readily prepared from R,R- or S,S BINOL and easily recovered from the reaction mixture by extraction. PMID- 22780431 TI - Interactions and binding energies of dimethyl methylphosphonate and dimethyl chlorophosphate with amorphous silica. AB - The fundamental interactions of dimethyl methylphosphonate (DMMP) and dimethyl chlorophosphate (DMCP) on amorphous silica nanoparticles have been investigated with transmission infrared spectroscopy and temperature-programmed desorption (TPD). DMMP and DMCP both adsorb molecularly to silica through the formation of hydrogen bonds between isolated silanols and the phosphoryl oxygen of the adsorbate. The magnitude of the shift of the nu(OH) mode upon simulant adsorption is correlated to the adsorption strength. The activation energies for desorption for a single DMMP or DMCP molecule from amorphous silica varied with coverage. In the limit of zero coverage, after the effects of defects were excluded, the activation energies were 54.5 +/- 0.3 and 48.4 +/- 1.0 kJ/mol for DMMP and DMCP, respectively. PMID- 22780432 TI - Internal desynchronization facilitates seizures. AB - PURPOSE: The occurrence of spike-wave discharges (SWDs) in WAG/Rij rats is modulated by the circadian timing system and is shaped by the presence of a light dark cycle, motor activity, and state of vigilance. Here it is investigated whether the response to a phase shift is different between the SWDs and general motor activity rhythm. The process of reentrainment of both rhythms and its effect on number of absences was compared after a phase shift in the light-dark cycle, a condition known to induce internal desynchronization in the circadian timing system. METHODS: Chronic electroencephalographic and motor activity recordings were made in adult WAG/Rij rats, kept in the 12:12 h light-dark cycle. After four baseline days, rats were exposed to an 8-h phase delay by shifting the light onset. Recordings were continuously made for another 10 consecutive days. KEY FINDINGS: An immediate effect of the phase shift on both rhythms was observed: the acrophases were 7.5 h advanced. Next, they gradually returned to the baseline level, however, with a different speed. The more robust motor activity rhythm stabilizes first, whereas the weaker rhythm of SWDs adapted more slowly. The phase shift caused a prolonged aggravation of epileptic activity, observed mostly during the light phase. SIGNIFICANCE: Different speed and character of reentrainment suggests that the occurrence of seizures and motor activity are controlled by distinct circadian oscillators. The prolonged increase in absences after the phase shift has immediate practical consequences. PMID- 22780433 TI - The 2011 Program Evaluation Standards: a framework for quality in medical education programme evaluations. AB - RATIONALE, AIMS AND OBJECTIVES: Based on input from 400 stakeholders over 6 years, the 2011 Program Evaluation Standards represents an in-depth analysis of values, meaning and measurement and their relationships in programme evaluation. Evaluation quality is achieved by balancing five attributes: utility, feasibility, propriety, accuracy and evaluation accountability. These attributes are used to organize 30 standards, 200 strategies and 197 hazards. METHOD: In response to a call from the authors of the standards, we have used them to guide our meta-evaluation of McGill's undergraduate physicianship programme. RESULTS: Our findings show how the standards illuminate the tensions, dilemmas and hazards inherent in all stages of programme evaluation studies and offer helpful strategies for designing and conducting high-quality evaluation studies. CONCLUSIONS: Based on our experience, the third edition needs to be used as a reference document in all stages of evaluations of medical education programmes. PMID- 22780434 TI - Size-tunable, fast, and facile synthesis of titanium oxide nanotube powders for dye-sensitized solar cells. AB - Size-tunable titanium oxide (TiO(2)) nanotube powders offering both a light scattering effect and a light-harvesting function were synthesized by a fast and facile anodizing method. When used to prepare the TiO(2) layer for a photoanode, their photovoltaic performances were much worse than that of a nanocrystal TiO(2) layer. However, when the TiO(2) nanotube powders were used as a light-scattering layer on a nanocrystal TiO(2) layer, the highest conversion efficiency was obtained because of more noticeable light absorption of the longer wavelength, which was not attainable from a pure nanocrystal TiO(2) layer or the combination of nanocrystal TiO(2)/commercialized light-scattering particles. PMID- 22780435 TI - Cortical and subcortical projections to primary visual cortex in anophthalmic, enucleated and sighted mice. AB - The purpose of this study was to identify and compare the afferent projections to the primary visual cortex in intact and enucleated C57BL/6 mice and in ZRDCT/An anophthalmic mice. Early loss of sensory-driven activity in blind subjects can lead to activations of the primary visual cortex by haptic or auditory stimuli. This intermodal activation following the onset of blindness is believed to arise through either unmasking of already present cortical connections, sprouting of novel cortical connections or enhancement of intermodal cortical connections. Studies in humans have similarly demonstrated heteromodal activation of visual cortex following relatively short periods of blindfolding. This suggests that the primary visual cortex in normal sighted subjects receives afferents, either from multisensory association cortices or from primary sensory cortices dedicated to other modalities. Here cortical afferents to the primary visual cortex were investigated to determine whether the visual cortex receives sensory input from other modalities, and whether differences exist in the quantity and/or the structure of projections found in sighted, enucleated and anophthalmic mice. This study demonstrates extensive direct connections between the primary visual cortex and auditory and somatosensory areas, as well as with motor and association cortices in all three animal groups. This suggests that information from different sensory modalities can be integrated at early cortical stages and that visual cortex activations following visual deprivations can partly be explained by already present intermodal corticocortical connections. PMID- 22780436 TI - Ultrasound diagnostics during acute circulatory disturbance in the perioperative or intensive care setting. PMID- 22780437 TI - Ephedrine for spinal hypotension during elective caesarean section: the final nail in the coffin? PMID- 22780441 TI - Aminoindolines versus quinolines: mechanistic insights into the reaction between 2-aminobenzaldehydes and terminal alkynes in the presence of metals and secondary amines. AB - DFT computational studies in the cyclization of aminoalkyne (see structure), which is generated in situ by 2-aminobenzaldehydes and terminal alkynes in the presence of metals and secondary amines, has been investigated. The study revealed that the mode of cyclization (exo vs endo) depends on the protecting group on nitrogen, the oxidation state of copper, and substitution on alkyne. PMID- 22780440 TI - Serum lipids modify periodontal infection - C-reactive protein association. AB - AIM: To investigate whether low-grade inflammation-related factors such as serum low-density (LDL-C) and high-density lipoprotein cholesterol (HDL-C) modify the association between periodontal infection and C-reactive protein. MATERIAL AND METHODS: This study was based on a subpopulation of the Health 2000 Survey, which consisted of dentate, non-diabetic, non-rheumatic subjects who were 30-49 years old (n = 2710). The extent of periodontal infection was measured by means of the number of teeth with periodontal pocket >=4 mm and teeth with periodontal pocket >=6 mm and systemic inflammation using high sensitive C-reactive protein. RESULTS: The extent of periodontal infection was associated with elevated levels of C-reactive protein among those subjects whose HDL-C value was below the median value of 1.3 mmol/l or LDL-C above the median value of 3.4 mmol/l. Among those with HDL-C >= 1.3 mmol/l or LDL-C <= 3.4 mmol/l, the association between periodontal infection and serum concentrations of C-reactive protein was practically non-existent. CONCLUSION: This study suggests that the relation of periodontal infection to the systemic inflammatory condition is more complicated than previously presumed. The findings of this study suggest that the possible systemic effect of periodontal infection is dependent on serum lipid composition. PMID- 22780442 TI - Innovation and technology for global public health. AB - Recent decades have been marked by the explosive development of innovative scientific, technological and business products and processes. Despite their immense impact on health globally, little has been accomplished in the field of global public health to incorporate, address and harness such innovations in practice. In order to meet the world's growing health needs, it is essential that global public health accepts and adapts to these innovations. Moreover, such innovations must be implemented equitably in ways that will best serve their intended recipients, without deepening health- and access-related disparities. This article will briefly discuss the wide array of technologies in the pipeline that will affect global public health practice, their impact on the field and on populations and the issues facing the field in adopting these innovations. PMID- 22780443 TI - Targeting TRPV1 for pain relief: limits, losers and laurels. AB - INTRODUCTION: With 336 reviews, the capsaicin receptor TRPV1 arguably represent today's most extensively reviewed analgesic target. TRPV1 is strategically located at the peripheral terminals of primary sensory neurons where pain is generated. TRPV1 as a target for analgesic drugs has been validated in preclinical studies. AREAS COVERED: The therapeutic potential of targeting TRPV1 by agonists and antagonists for pain relief is discussed based on our experience and a critical review of the literature. Strategies to overcome adverse effects are explored. EXPERT OPINION: Since its discovery in 1997, TRPV1 has run the gamut from excitement to disappointment to cautious optimism. Topical capsaicin has been disappointing for pain relief. By contrast, intrathecal resiniferatoxin is currently undergoing clinical trials in patients with intractable cancer pain. Some of the small-molecule TRPV1 antagonists have successfully passed Phase I safety and tolerability studies in healthy volunteers into Phase II studies to access efficacy in patients. Others showed worrisome unforeseen adverse effects, most important, hyperthermia and impaired noxious heat sensation. We conclude that TRPV1 blockade and desensitization are two promising, complimentary approaches for pain relief. Despite the roadblocks, TRPV1 remains a powerful tool in pain research and a promising therapeutic target. PMID- 22780444 TI - Two CheW coupling proteins are essential in a chemosensory pathway of Borrelia burgdorferi. AB - In the model organism Escherichia coli, the coupling protein CheW, which bridges the chemoreceptors and histidine kinase CheA, is essential for chemotaxis. Unlike the situation in E. coli, Borrelia burgdorferi, the causative agent of Lyme disease, has three cheW homologues (cheW(1) , cheW(2) and cheW(3) ). Here, a comprehensive approach is utilized to investigate the roles of the three cheWs in chemotaxis of B. burgdorferi. First, genetic studies indicated that both the cheW(1) and cheW(3) genes are essential for chemotaxis, as the mutants had altered swimming behaviours and were non-chemotactic. Second, immunofluorescence and cryo-electron tomography studies suggested that both CheW(1) and CheW(3) are involved in the assembly of chemoreceptor arrays at the cell poles. In contrast to cheW(1) and cheW(3) , cheW(2) is dispensable for chemotaxis and assembly of the chemoreceptor arrays. Finally, immunoprecipitation studies demonstrated that the three CheWs interact with different CheAs: CheW(1) and CheW(3) interact with CheA(2) whereas CheW(2) binds to CheA(1) . Collectively, our results indicate that CheW(1) and CheW(3) are incorporated into one chemosensory pathway that is essential for B. burgdorferi chemotaxis. Although many bacteria have more than one homologue of CheW, to our knowledge, this report provides the first experimental evidence that two CheW proteins coexist in one chemosensory pathway and that both are essential for chemotaxis. PMID- 22780446 TI - Differential effects of trait anger on optimism and risk behaviour. AB - It has been proposed that angry people exhibit optimistic risk estimates about future events and, consequently, are biased towards making risk-seeking choices. The goal of this study was to directly test the hypothesised effect of trait anger on optimism and risk-taking behaviour. One hundred healthy volunteers completed questionnaires about personality traits, optimism and risk behaviour. In addition their risk tendency was assessed with the Balloon Analogue Risk Task (BART), which provides an online measure of risk behaviour. Our results partly confirmed the relation between trait anger and outcome expectations of future life events, but suggest that this optimism does not necessarily translate into actual risk-seeking behaviour. PMID- 22780445 TI - Surface-enhanced Raman scattering of whole human blood, blood plasma, and red blood cells: cellular processes and bioanalytical sensing. AB - SERS spectra of whole human blood, blood plasma, and red blood cells on Au nanoparticle SiO(2) substrates excited at 785 nm have been observed. For the sample preparation procedure employed here, the SERS spectrum of whole blood arises from the blood plasma component only. This is in contrast to the normal Raman spectrum of whole blood excited at 785 nm and open to ambient air, which is exclusively due to the scattering of oxyhemoglobin. The SERS spectrum of whole blood shows a storage time dependence that is not evident in the non-SERS Raman spectrum of whole blood. Hypoxanthine, a product of purine degradation, dominates the SERS spectrum of blood after ~10-20 h of storage at 8 degrees C. The corresponding SERS spectrum of plasma isolated from the stored blood shows the same temporal release of hypoxanthine. Thus, blood cellular components (red blood cells, white blood cells, and/or platelets) are releasing hypoxanthine into the plasma over this time interval. The SERS spectrum of red blood cells (RBCs) excited at 785 nm is reported for the first time and exhibits well-known heme group marker bands as well as other bands that may be attributed to cell membrane components or protein denaturation contributions. SERS, as well as normal Raman spectra, of oxy- and met-RBCs are reported and compared. These SERS results can have significant impact in the area of clinical diagnostics, blood supply management, and forensics. PMID- 22780447 TI - Reproductive seasonality in captive wild ruminants: implications for biogeographical adaptation, photoperiodic control, and life history. AB - Many ruminant species show seasonal patterns of reproduction. Causes for this are widely debated, and include adaptations to seasonal availability of resources (with cues either from body condition in more tropical, or from photoperiodism in higher latitude habitats) and/or defence strategies against predators. Conclusions so far are limited to datasets with less than 30 species. Here, we use a dataset on 110 wild ruminant species kept in captivity in temperate-zone zoos to describe their reproductive patterns quantitatively [determining the birth peak breadth (BPB) as the number of days in which 80% of all births occur]; then we link this pattern to various biological characteristics [latitude of origin, mother-young-relationship (hider/follower), proportion of grass in the natural diet (grazer/browser), sexual size dimorphism/mating system], and compare it with reports for free-ranging animals. When comparing taxonomic subgroups, variance in BPB is highly correlated to the minimum, but not the maximum BPB, suggesting that a high BPB (i.e. an aseasonal reproductive pattern) is the plesiomorphic character in ruminants. Globally, latitude of natural origin is highly correlated to the BPB observed in captivity, supporting an overruling impact of photoperiodism on ruminant reproduction. Feeding type has no additional influence; the hider/follower dichotomy, associated with the anti-predator strategy of 'swamping', has additional influence in the subset of African species only. Sexual size dimorphism and mating system are marginally associated with the BPB, potentially indicating a facilitation of polygamy under seasonal conditions. The difference in the calculated Julian date of conception between captive populations and that reported for free-ranging ones corresponds to the one expected if absolute day length was the main trigger in highly seasonal species: calculated day length at the time of conception between free-ranging and captive populations followed a y = x relationship. Only 11 species (all originating from lower latitudes) were considered to change their reproductive pattern distinctively between the wild and captivity, with 10 becoming less seasonal (but not aseasonal) in human care, indicating that seasonality observed in the wild was partly resource-associated. Only one species (Antidorcas marsupialis) became more seasonal in captivity, presumably because resource availability in the wild overrules the innate photoperiodic response. Reproductive seasonality explains additional variance in the body mass-gestation period relationship, with more seasonal species having shorter gestation periods for their body size. We conclude that photoperiodism, and in particular absolute day length, are genetically fixed triggers for reproduction that may be malleable to some extent by body condition, and that plasticity in gestation length is an important facilitator that may partly explain the success of ruminant radiation to high latitudes. Evidence for an anti-predator strategy involving seasonal reproduction is limited to African species. Reproductive seasonality following rainfall patterns may not be an adaptation to give birth in periods of high resource availability but an adaptation to allow conception only at times of good body condition. PMID- 22780449 TI - Safety in the use of dexmedetomidine (precedex) for deep brain stimulation surgery: our experience in 23 randomized patients. AB - OBJECTIVE: Evaluation of safety and efficacy of dexmedetomidine in deep brain stimulation (DBS) surgery. MATERIALS AND METHODS: A cohort of 23 patients, candidates for DBS for Parkinson's disease, Tourette syndrome, or obsessive compulsive disorder, was randomized in two groups: dexmedetomidine group and control group. Standard anesthesiologic parameters were recorded and analyzed, together with the need for other medications. A ten-degree scale (visual analog scale) assessing patient discomfort during DBS also was recorded at the end of surgery. RESULTS: The results demonstrated good stability of intraoperative monitoring: no respiratory depression and good overall cooperation with the neurologist, while no side-effects were recorded. CONCLUSIONS: Our conclusion is that dexmedetomidine should be considered as a valuable option for sedation in poorly collaborating patients undergoing DBS surgery. PMID- 22780451 TI - Chlorination of aliphatic primary alcohols via triphosgene-triethylamine activation. AB - Activation of primary aliphatic alcohols with triphosgene and triethylamine mixtures afforded either alkyl chloride or diethylcarbamate products, and the switch in selectivity appeared to be driven by sterics. The reaction conditions to achieve this highly useful transformation were unexceptionally mild and readily tolerated by a wide range of sensitive functionalities. PMID- 22780450 TI - Gene-by-preschool interaction on the development of early externalizing problems. AB - BACKGROUND: Preschool involves an array of new social experiences that may impact the development of early externalizing behavior problems over the transition to grade school. METHODS: Using longitudinal data from a nationally representative sample of over 600 pairs of US twins, we tested whether the genetic and environmental influences on externalizing problems differed between children who did versus did not attend preschool. RESULTS: At age 4, the genetic and environmental etiology of externalizing did not differ by preschool attendance. In contrast, by age 5 years (kindergarten age), the genetic and environmental etiology of externalizing significantly differed by preschool attendance. Among children who did not attend preschool, externalizing at age 5 was predominantly due to environmental influences (52% shared environment, 34% non-shared environment) rather than genetic differences (13%), whereas among children who had attended preschool, externalizing at age 5 was primarily due to genes (67%), and shared environmental influences were negligible (0%). These interactions represented the differential longitudinal persistence of genes and environments that contributed to externalizing at age 4. Sensitivity analyses ruled out confounding due to early mental ability, socioeconomic status, minority status, child age, and prior history of childcare. CONCLUSIONS: These results indicate that preschool enrollment is associated with increased genetic and decreased shared environmental influences on the development of early externalizing behavior problems. PMID- 22780452 TI - Spectroscopic and electrochemical study of the interconversion and decomplexation of cobalt(II) sandwich polyoxometalates based on a Dawson-type anion. AB - The reaction of the trivacant Dawson polyoxometalate alpha-[P(2)W(15)O(56)](12-) and the divalent cations Co(2+) is known to form a symmetrically derived sandwich complex of formula betabeta-[Co(4)(H(2)O)(2)(P(2)W(15)O(56))(2)](16-) [symbolized as betabeta-Co(4)(P(2)W(15))(2)] at low pH (ca. pH 3). We have shown previously that, by a slight modification of the reaction conditions, trinuclear alphabeta [(NaOH(2))Co(3)(H(2)O)(P(2)W(15)O(56))(2)](17-) and dinuclear [(NaOH(2))(2)Co(2)(P(2)W(15)O(56))(2)](18-) complexes [symbolized as alphabeta NaCo(3)(P(2)W(15))(2) and Na(2)Co(2)(P(2)W(15))(2), respectively] can be synthesized as aqueous-soluble sodium salts. alphabeta-NaCo(3)(P(2)W(15))(2) is a "lacunary" sandwich complex that can add a Co(2+) cation to form nearly quantitatively an unsymmetrical Dawson tetracobalt sandwich polyoxometalate, alphabeta-[Co(4)(H(2)O)(2)(P(2)W(15)O(56))(2)](16-) [symbolized as alphabeta Co(4)(P(2)W(15))(2)]. Thus, for Co(4)(P(2)W(15))(2), the junctions between the trivacant {P(2)W(15)} subunits and the central tetrameric unit can be either both beta type or beta and alpha types. The interconversion between alphabeta Co(4)(P(2)W(15))(2) and betabeta-Co(4)(P(2)W(15))(2) and the decomplexation process at low pH, leading to the formation of alphabeta-NaCo(3)(P(2)W(15))(2) and/or Na(2)Co(2)(P(2)W(15))(2), have been followed in aqueous solution at various pH values by electrochemistry, UV-visible absorption spectroscopy, and (31)P NMR spectroscopy. PMID- 22780453 TI - Clinic-based ultrasound can predict malignancy in pediatric thyroid nodules. AB - BACKGROUND: Thyroid nodules in pediatric patients may carry a greater risk for malignancy than in adults. Most nodules >1 cm in patients <= 21 years of age may require thyroidectomy for definitive diagnosis and treatment. Although clinic based ultrasound (CBUS) has been shown useful in the evaluation of thyroid nodules in adults, its utility in evaluating nodules in the pediatric population remains unclear. METHODS: Prospectively collected data regarding 50 patients <= 21 years who underwent preoperative CBUS and initial thyroidectomy at a single institution were retrospectively reviewed. All CBUS were performed by endocrine surgeons certified in basic and cervical ultrasonography. Preoperative CBUS characteristics of pediatric thyroid nodules were analyzed with respect to final pathology. RESULTS: Of the 50 patients <= 21 years of age who underwent surgical resection for a dominant thyroid nodule, there were 45 females and 5 males with an average age of 17.4 years (range: 10-21 years). On univariate analysis, microcalcifications (p<0.001), abnormal lymph nodes (p<0.001), and dimensions taller more than wide (p=0.033) were individual CBUS characteristics predictive of thyroid malignancy. All nine patients with abnormal lymph nodes on CBUS had malignant disease on final pathology. Multiple thyroid nodules, a cystic component, and echogenicity did not predict malignancy; regular borders trended toward predicting a benign nodule (p=0.066). When malignant ultrasound features were considered (i.e., hypoechoic, irregular borders, microcalcifications, abnormal lymph nodes, and shape taller more than wide), having one malignant feature predicted malignancy with an odds ratio of 2.0 while having >= 2 features held even greater significance (p=0.004, OR 4.0). All patients with >= 3 malignant ultrasound features had thyroid cancer on final pathology. CONCLUSION: CBUS is a useful diagnostic modality in determining malignancy status of thyroid nodules in patients <= 21 years of age. CBUS should be employed as part of an initial assessment of any pediatric patient presenting with thyroid nodules to help further guide management and treatment. PMID- 22780454 TI - Do parents understand the medical information provided in paediatric emergency departments? A prospective multicenter study. AB - AIM: We evaluated the extent to which parents understood the medical information about hospitalization of their child in an emergency department and looked for characteristics likely to increase the risk of poor comprehension. METHODS: Prospective multicenter study in thirteen paediatric emergency departments. The parents and doctors completed questionnaires based on closed ended questions with a common core of four items: reasons of hospitalization, diagnosis, treatment and seriousness of child condition. We evaluated concordance between parents and doctor answers for these items by comparing their responses. RESULTS: This study included 380 parents. Percentage of concordance was 55% for the reason of hospitalization, 78% for the diagnosis, 92% for the treatment, 48% for the seriousness of the condition and 19% for all four items. The mean number of concordant items was 2.76 (CI 95%, 2.66-2.86). Parents whose children seemed not in pain and parents who received additional information from the nurse showed significantly slightly higher levels of concordance with doctor's answers (2.98 vs 2.66, p = 0.006 and 2.89 vs 2.60, p = 0.004, respectively). CONCLUSION: This study shows that improvements are required in the clarity of the information delivered to the parents. The assistance of nurses and optimal pain management may help to improve communication. PMID- 22780456 TI - An intramolecular G-quadruplex structure is required for binding of telomeric repeat-containing RNA to the telomeric protein TRF2. AB - Telomeric repeat-containing RNA (TERRA) is important for telomere regulation, but the structural basis for how TERRA localizes to chromosome ends is unknown. Here we report on studies exploring whether the TERRA G-quadruplex structure is critical for binding to telomeres. We demonstrate that the telomeric protein TRF2 binds TERRA via interactions that necessitate the formation of a G-quadruplex structure rather than the TERRA sequence per se. We also show that TRF2 simultaneously binds TERRA and telomeric duplex or G-quadruplex DNA. These observations suggest that the TERRA G-quadruplex is a key feature of telomere organization. PMID- 22780455 TI - Growth as a mirror: is endocrine disruption challenging Tanner's concept? AB - BACKGROUND: James Tanner coined the expression 'Growth as a Mirror' and summarized in four words the results of more than a century of research on growth. Nineteenth century social reformers saw poor child growth as a reflection of terrible environmental conditions of the working class. Later investigators in anthropology and other fields clarified the connections between poor nutrition, disease, psychosocial stress and poor growth. AIM: To evaluate the growth as a mirror concept in light of recent studies of endocrine disruption. PAPERS AND IMPLICATIONS: Pollution is recognized as a prominent component of the modern environment. From studies of many pollutants it is clear that some pollutants depress growth while others speed sexual maturation and increase growth, primarily in weight and fatness. While such unwelcome environmental features do not always suppress growth, growth still mirrors the environment in all its complexity and this relationship is key to understanding growth patterns today. For example, Akwesasne Mohawk adolescents are characterized by high rates of obesity and overweight. Their growth reflects the multiple intersecting influences of psychosocial stress, several pollutant exposures and limited dietary choices. CONCLUSION: Although Tanner did not anticipate the myriad influences of pollutants, the growth as a mirror concept continues to have great validity and utility. PMID- 22780551 TI - Dacrystic seizures: demographic, semiologic, and etiologic insights from a multicenter study in long-term video-EEG monitoring units. AB - PURPOSE: To provide an estimate of the frequency of dacrystic seizures in video electroencephalography (EEG) long-term monitoring units of tertiary referral epilepsy centers and to describe the clinical presentation of dacrystic seizures in relationship to the underlying etiology. METHODS: We screened clinical records and video-EEG reports for the diagnosis of dacrystic seizures of all patients admitted for video-EEG long-term monitoring at five epilepsy referral centers in the United States and Germany. Patients with a potential diagnosis of dacrystic seizures were identified, and their clinical charts and video-EEG recordings were reviewed. We included only patients with: (1) stereotyped lacrimation, sobbing, grimacing, yelling, or sad facial expression; (2) long-term video-EEG recordings (at least 12 h); and (3) at least one brain magnetic resonance imaging (MRI) study. KEY FINDINGS: Nine patients (four female) with dacrystic seizures were identified. Dacrystic seizures were identified in 0.06-0.53% of the patients admitted for long-term video-EEG monitoring depending on the specific center. Considering our study population as a whole, the frequency was 0.13%. The presence of dacrystic seizures without other accompanying clinical features was found in only one patient. Gelastic seizures accompanied dacrystic seizures in five cases, and a hypothalamic hamartoma was found in all of these five patients. The underlying etiology in the four patients with dacrystic seizures without gelastic seizures was left mesial temporal sclerosis (three patients) and a frontal glioblastoma (one patient). All patients had a difficult-to-control epilepsy as demonstrated by the following: (1) at least three different antiepileptic drugs were tried in each patient, (2) epilepsy was well controlled with antiepileptic drugs in only two patients, (3) six patients were considered for epilepsy surgery and three of them underwent a surgical/radiosurgical or radioablative procedure. Regarding outcome, antiepileptic drugs alone achieved seizure freedom in two patients and did not change seizure frequency in another patient. Radiosurgery led to moderately good seizure control in one patient and did not improve seizure control in another patient. Three patients were or are being considered for epilepsy surgery on last follow-up. One patient remains seizure free 3 years after epilepsy surgery. SIGNIFICANCE: Dacrystic seizures are a rare but clinically relevant finding during video-EEG monitoring. Our data show that when the patient has dacrystic and gelastic seizures, the cause is a hypothalamic hamartoma. In contrast, when dacrystic seizures are not accompanied by gelastic seizures the underlying lesion is most commonly located in the temporal cortex. PMID- 22780552 TI - Adsorption and electron-induced dissociation of ethanethiol on Au(111). AB - Dissociation of ethanethiol and the formation of Au-adatom-diethylthiolate rows on the Au(111) surface were investigated using scanning tunneling microscopy (STM) at low temperature. Ethanethiol molecules physisorb on Au(111) at 120 K by sequentially occupation of the elbow site, the fcc domain before covering the whole surface with a semiliquid layer without long-range order. Scanning the physisorbed layer with a sample bias higher than +1.2 V leads to dissociation via cleaving the H-S bond. One of the dissociation products, ethylthiolate, forms a double-row structure with the rows aligned in one of the [112(-)] directions. These double rows arise from the Au-adatom-dithiolate species: CH(3)CH(2)S-Au SCH(2)CH(3). PMID- 22780553 TI - Modulation of polymer refractive indices with diamond nanoparticles for metal free multilayer film mirrors. AB - Modulation of the refractive index of a polymer was achieved by combining it with diamond nanoparticles (NDs). The increase in the refractive index was controlled by the amount of NDs added, according to the Lorentz-Lorenz equation. The refractive index of poly(vinyl alcohol) (PVA), which was used as the base polymer, increased from 1.52 to 1.88. A multilayer film consisting of alternating layers of ND-PVA composite and poly(methyl methacrylate) exhibited ca. 80% reflectance with 10 bilayers. PMID- 22780554 TI - The role of dopamine in the accumbens core in the expression of Pavlovian conditioned responses. AB - The role of dopamine in reward is a topic of debate. For example, some have argued that phasic dopamine signaling provides a prediction-error signal necessary for stimulus-reward learning, whereas others have hypothesized that dopamine is not necessary for learning per se, but for attributing incentive motivational value ('incentive salience') to reward cues. These psychological processes are difficult to tease apart, because they tend to change together. To disentangle them we took advantage of natural individual variation in the extent to which reward cues are attributed with incentive salience, and asked whether dopamine (specifically in the core of the nucleus accumbens) is necessary for the expression of two forms of pavlovian-conditioned approach behavior--one in which the cue acquires powerful motivational properties (sign-tracking) and another closely related one in which it does not (goal-tracking). After acquisition of these conditioned responses (CRs), intra-accumbens injection of the dopamine receptor antagonist flupenthixol markedly impaired the expression of a sign tracking CR, but not a goal-tracking CR. Furthermore, dopamine antagonism did not produce a gradual extinction-like decline in behavior, but maximally impaired expression of a sign-tracking CR on the very first trial, indicating the effect was not due to new learning (i.e. it occurred in the absence of new prediction error computations). The data support the view that dopamine in the accumbens core is not necessary for learning stimulus-reward associations, but for attributing incentive salience to reward cues, transforming predictive conditional stimuli into incentive stimuli with powerful motivational properties. PMID- 22780556 TI - Do self-assessments of health predict future mortality in rural South Africa? The case of KwaZulu-Natal in the era of antiretroviral treatment. AB - OBJECTIVES: While self-assessments of health (SAH) are widely employed in epidemiological studies, most of the evidence on the power of SAH to predict future mortality originates in the developed world. With the HIV pandemic affecting largely prime age individuals, the strong association between SAH and mortality derived from previous work might not be relevant for the younger at risk groups in countries with high HIV prevalence in the era of antiretroviral treatment. We investigate the power of SAH to predict mortality in a community with high HIV prevalence and antiretroviral treatment (ART) coverage using linked data from three sources: a longitudinal demographic surveillance, one of Africa's largest, longitudinal, population-based HIV surveillances, and a decentralised rural HIV treatment and care programme. METHODS: We used a Cox proportional hazards specification to examine whether SAH significantly predicts mortality hazard in a sample composed of 9217 adults aged 15-54, who were followed up for mortality for 8 years. RESULTS: Self-assessments of health strongly predicted mortality (within 4 years of follow-up), with a clear gradient of the adjusted hazard ratios (aHRs), relative to the baseline of 'excellent' self-assessed health status and controlling for age, gender, marital status, the socio-economic status (SES), variables education, employment, household expenditures and household assets, and HIV status and ART uptake: 1.40 (95% CI 0.99-1.96) for 'very good' self-assessed health status (SAHS); 2.10 (95% CI 1.52-2.90) for 'good' SAHS; 3.12 (95% CI 2.18-4.45) for 'fair' SAHS; and 4.64 (95% CI 2.93-7.35) for 'poor' SAHS. While a similar association remained in the unadjusted analysis of long-term mortality (within 4-8 years of follow-up) the hazard ratios capturing SAH are jointly insignificant in predicting of mortality once HIV status, ART uptake and gender, age, marital status and SES were controlled for. HIV status and ART programme participation were large and highly significant predictors of long-term mortality. CONCLUSIONS: Our findings validate SAH as a variable that significantly predicts short-term mortality in a community in sub Saharan Africa with high HIV prevalence, morbidity and mortality. When predicting long-term mortality, however, it is much more important to know a person's HIV status and ART programme participation than SAH. PMID- 22780557 TI - Predictors of inter-proximal and midfacial recession following single implant treatment in the anterior maxilla: a multivariate analysis. AB - PURPOSE: A number of factors have been associated with soft tissue recession following single implant treatment. However, given the cross-sectional design of most of these studies and crude associations based on univariate analyses, such factors may only be considered risk indicators. The objective of the present retrospective cohort study using multivariate analyses was to identify predictors of recession. MATERIAL AND METHODS: Patients who had been treated by two periodontists and two prosthodontists in 2006 and 2007 for a single implant in the anterior maxilla were re-examined in 2009 and their records were scrutinized. Subjects treated via flap surgery with and without ridge re-contouring were considered. Outcome variables were inter-proximal and midfacial recession. Explanatory variables included demographic data, the surgical approach and a number of local factors that were evaluated on radiographs taken pre-operatively or at permanent crown installation (baseline). RESULTS: Data pertaining to 97/115 (60 females, 37 males; mean age 51, SD 13, range 23-80) patients were available for evaluation. Significant bone loss was observed between baseline and re examination at the implant surface (0.2-0.3 mm, p < 0.001) and tooth surface (0.3 0.5 mm, p < 0.001). Surgery with ridge re-contouring demonstrated 0.2 mm additional bone loss at the distal tooth surface when compared to surgery without ridge re-contouring (p = 0.034). This could be explained by a disparity in possible papilla-opening procedures (three versus one or two). As a result, regression analyses identified surgery with ridge re-contouring as a predictor of inter-proximal recession (OR >= 3.4). Pre-operative bone level at the tooth surface was another predictor of inter-proximal recession (OR >= 2.1). Recession of the distal papilla was also affected by a missing contact point (OR = 221.9), the implant-to-tooth distance (OR = 0.3) and the distance of the bone peak to the contact point (OR = 2.9). Midfacial recession was only associated with a buccal shoulder position (OR = 17.2). CONCLUSIONS: To optimize soft tissue levels around single implants, clinicians should limit papilla-opening procedures and pay utmost attention to a correct implant and contact point positioning. PMID- 22780558 TI - A possible chemopreventive role for photodynamic therapy in Gorlin syndrome: a report of basal cell carcinoma reduction and review of literature. AB - Multiple basal cell carcinomas (BCC) are a significant cause of morbidity and disfigurement in patients with naevoid basal cell carcinoma syndrome (NBCCS). Chemopreventive strategies are needed to reduce the formation of new BCC in these patients. Appropriate evidence-based guidelines for photodynamic therapy chemoprevention in NBCCS do not exist. We herein report one patient treated with methyl aminolevulinate PDT with red light (630 nm) activation to continue sustained chemoprevention following other BCC chemopreventive modalities and a relevant literature review. PMID- 22780559 TI - Aromatic cations from oxidative carbon-hydrogen bond cleavage in bimolecular carbon-carbon bond forming reactions. AB - Chromenes and isochromenes react quickly with 2,3-dichloro-5,6-dicyano-1,4 benzoquinone (DDQ) to form persistent aromatic oxocarbenium ions through oxidative carbon-hydrogen cleavage. This process is tolerant of electron-donating and electron-withdrawing groups on the benzene ring and additional substitution on the pyran ring. A variety of nucleophiles can be added to these cations to generate a diverse set of structures. PMID- 22780560 TI - Melatonin with 1,25-dihydroxyvitamin D3 protects against apoptotic ischemia reperfusion injury in the rat kidney. AB - This study was designed to evaluate the preventive role of melatonin (Mel) and 1,25-dihydroxyvitamin D3 (VD3) in biochemical and apoptotic events leading to tissue injury and renal dysfunction after ischemia-reperfusion (I/R). Thirty male Wistar rats were divided into five groups: sham-operated, I/R, Mel + I/R, VD3 + I/R, and Mel + VD3 + I/R. The rats were intraperitoneally administered with Mel (10 mg/kg), VD3 (0.5 MUg/kg), or Mel (10 mg/kg) plus VD3 (0.5 MUg/kg) each day at 1 week prior to ischemia. Right nephrectomy was initially performed and left renal I/R injury was induced by 45 min of bilateral renal ischemia followed by 45 min of reperfusion. After reperfusion, kidneys and blood were obtained for histopathologic and biochemical evaluation. Mel and VD3 had an ameliorative effect on biochemical parameters such as serum creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, and apoptosis (caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining) in the kidneys against renal I/R injury in rats. Additionally, VD3 combined with Mel significantly reduced apoptotic and histological alterations when compared with Mel or VD3 alone. This preventive effect on renal tubular apoptosis was remarkable when Mel was combined with VD3. PMID- 22780561 TI - Emerging drugs for the treatment of sepsis. AB - INTRODUCTION: Despite improvement in medical care, severe sepsis and septic shock remain an unmet medical need. Their incidence is steadily increasing and the worldwide mortality ranges between 30% and 50%. This generates the need for agents that modulate the immune function of the host. AREAS COVERED: Available agents can be divided into three categories according to their mechanism of action: i) agents that block bacterial products and inflammatory mediators. Hemoperfusion with polymyxin B embedded fiber device that blocks bacterial lipopolysaccharides (LPS) has given promising clinical results. Blockade of TNF alpha with afelimomab and CytoFab appears promising; ii) modulators of immune function. Hydrocortisone stress replacement, intravenous infusion of clarithromycin and immunonutrition with omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) have all yielded positive clinical results. Recombinant thrombomodulin for patients with disseminated intravascular coagulation appears a promising alternative; and iii) immunostimulation. Meta-analysis of conducted trials disclosed the decrease of mortality in septic shock after administration of immunoglobulin preparations enriched with IgM. EXPERT OPINION: The underlying pathophysiologic mechanisms in septic patients are highly individualized. As such, specific tools should be developed in the near future to define these differences and tailor therapeutic strategies accordingly. PMID- 22780562 TI - Interaction of the Escherichia coli transporter DctA with the sensor kinase DcuS: presence of functional DctA/DcuS sensor units. AB - The aerobic Escherichia coli C(4) -dicarboxylate transporter DctA and the anaerobic fumarate/succinate antiporter DcuB function as obligate co-sensors of the fumarate responsive sensor kinase DcuS under aerobic or anaerobic conditions respectively. Overproduction under anaerobic conditions allowed DctA to replace DcuB in co-sensing, indicating their functional equivalence in this capacity. In vivo interaction studies between DctA and DcuS using FRET or a bacterial two hybrid system (BACTH) demonstrated their interaction. DctA-YFP bound to an affinity column and was able to retain DcuS. DctA shows substantial sequence and secondary structure conservation to Glt(Ph), the Na(+)/glutamate symporter of Pyrococcus horikoshii with known 3D structure. Topology studies of DctA demonstrated the presence of eight transmembrane helices in an arrangement similar to that of Glt(Ph) . DctA contains an additional predicted amphipathic helix 8b on the cytoplasmic side of the membrane that is specific for DctA and not present in Glt(Ph). Mutational analysis demonstrated the importance of helix 8b in co-sensing and interaction with DcuS, and the isolated helix 8b showed strong interaction with DcuS. In DcuS, deletion and mutation of the cytoplasmic PAS(C) domain affected the interaction between DctA and DcuS. It is concluded that DctA forms a functional unit or sensor complex with DcuS through specific interaction sites. PMID- 22780563 TI - Hydrothermally mixed hydroxyapatite-multiwall carbon nanotubes composite coatings on biomedical alloys by electrophoretic deposition. AB - Hydroxyapatite (HA) coatings have been used to improve biological and mechanical fixation of metallic prosthesis. Because of extraordinary features of carbon nanotubes (CNTs), they have a lot of facilities, such as extremely strong nanoreinforcement materials for composites. HA powders were synthesized and mixed with multiwalled carbon nanotubes (MWCNTs) by a hydrothermal process. Calcium acetate (Ca (CH(3)COO)(2)) and phosphoric acid (H(3)PO(4)) were used as starting materials for synthesizing nano-HA powders. HA-MWCNTs were treated together hydrothermally at 200 degrees C for 2 h to synthesize nano-HA powders mixed homogeneously with MWCNTs. Cathodic deposits were obtained on Ti-based alloys using suspensions containing nano-HA and MWCNTs dispersed in n-butanol solvent. It was shown that MWCNTs interacted with HA powders during hydrothermal processing, and therefore, they can easily be dispersed within aqueous-based suspensions. It was also shown that hydrothermal surface modification of MWCNTs with functional groups was achievable, which was a significant step toward eliminating nonwetting surface behavior of MWCNTs, resulting in obtaining homogeneous dispersion of them in liquids. PMID- 22780565 TI - Admiration and adoration: their different ways of showing and shaping who we are. AB - Admiration and adoration have been considered as emotions with the power to change people, yet our knowledge of the specific nature and function of these emotions is quite limited. From an interdisciplinary perspective, we present a prototype approach to admiration and what has variously been labelled adoration, worship, or reverence. Both admiration and adoration contribute to the formation of personal and collective ideals, values, and identities, but their workings differ. We offer a detailed theoretical account of commonalities and differences in the appraisal patterns and action tendencies associated with the two emotions. This analysis reveals that admiration motivates the internalisation and emulation of ideals embodied by an outstanding role model. Adoration motivates adherence to the teachings and expectations of a meaning maker and benefactor perceived as superhuman or sacred. Thus, the primary function of admiration is to promote individual learning and change, whereas adoration primarily serves to bind communities together. PMID- 22780566 TI - The relationship between age and morphine infusion rate in children. AB - AIM: We performed a retrospective audit of intravenous morphine infusion administered to children in an effort to characterize the relationship between dose and age. METHODS: A retrospective audit of morphine infusions was reviewed for a 24-months period and included all children who received continuous intravenous nurse-controlled morphine infusions and patient-controlled analgesia; a population undergoing acute and elective surgical procedures, as well as medical and oncological treatments. The relationship between age and infusion rate was investigated using nonlinear mixed effects models. RESULTS: There were 886 children whose data were acceptable for review. Morphine dose increased with age from 9.97 (CV 28%) MUg . kg(-1) per h in neonates. The Hill equation with an exponential of 1.5 best described these changes. Morphine rate reached 90% of its mean final rate of 22.5 (CV 167%) MUg . kg(-1) per h, observed in teenagers, at approximately 5 years of age. There was considerable uncertainty of this age morphine rate profile, and the maturation half-life of this profile was 20 months of age (CV 632%). An increase in dosing variability was observed with increasing age. CONCLUSIONS: Morphine infusions at steady-state did not mirror clearance maturation in children nursed in our hospital. We suggest that initial infusion rates in children are started at 10 MUg . kg(-1) per h in neonates, 15 MUg . kg( 1) per h in toddlers and 25 MUg . kg(-1) per h in children above the age of 5 years. The large variability associated with infusion rates means that subsequent infusion rates will depend on feedback from pain scores, adjuvant medications and adverse effects. PMID- 22780567 TI - Evaluation of a shared approach to interprofessional learning about stroke self management. AB - This article describes an evaluation of interprofessional training in a stroke self-management program (SSMP) for health and social care professionals. Sixty six practitioners from 8 teams and 11 professions received training. The aim was to evaluate the impact of the interprofessional training on participants' beliefs and attitudes to self-management and collaboration and knowledge sharing throughout the stroke pathway. Methods included contextual mapping of the stroke pathway, before and after questionnaires, analysis of practitioners' case reflections on their use of the SSMP and semi-structured interviews. Overall, practitioners' attitudes and beliefs about self-management had changed post training, and the majority felt the program could be used successfully throughout the stroke pathway. Practitioners felt that the interprofessional training had led to a more consistent approach to supporting self-management and had improved communication between teams about patients/goals. The project provided the opportunity for interprofessional teams to explore beliefs and attitudes to changes in practice together. PMID- 22780568 TI - Interprofessional aspects of the dignity in care program in Wales. AB - Wales is one of constituent countries of the UK and a Dignity in Care Program was launched in 2007. In this retrospective thematic review paper, interprofessional aspects are considered in the 6 training events, 3 listening events and 22 small projects delivered within the program. While there was good professional engagement with the program, the actual impact on health and social care service provision is difficult to evidence. One of the future challenges in Wales might be to develop a prospective performance management system for dignity in care which measures impact rather than proxy measures of engagement. PMID- 22780569 TI - Working in "teams" in an era of "liquid" healthcare: what is the use of theory? AB - "Team" is used throughout the healthcare literature as if it had a transparent, single meaning, and in policy documents it has become a mantra. Yet, "team" is a contested and imprecise term, inviting theoretical sophistication. New forms of team working in healthcare contexts can be understood as a complex set of practices and a discourse--both performed, and written and talked about as a supplementary practice. In the context of fluid and unpredictable social conditions, teams are now theorized in terms of contradictory process as well as stable membership. Cultural-historical activity theory in particular provides a rich approach to understanding such process, in an era where the desire for stable networks--a will-to-stability--may be secondary to the need for a will-to adaptability. A new vocabulary has emerged in theoretical accounts to describe activities of an emergent work order, in terms of a shift from stable "networking" to unstable "knotworking." However, this conceptual language can be overwrought and may alienate practitioners. Theory can be developed with practitioners themselves to avoid widening the gap between experience and the understanding and explanation of experience. Teams are not problems to be solved but activities to be expanded. PMID- 22780570 TI - Efficacy of sardinelle protein hydrolysate to alleviate ethanol-induced oxidative stress in the heart of adult rats. AB - The present study was undertaken to examine the protective effects of sardinelle proteins hydrolysate (SPH) obtained from heads and viscera against ethanol toxicity in the heart of adult rats. Twenty-four male rats of Wistar strain, weighing at the beginning of the experiment 250 to 300 g, were used in this study. They were divided into 4 groups: group (C) served as controls, group (Eth) received 30% ethanol solution at 3 g/kg body weight, group (SPH) received only 7.27 mg of SPH/kg body weight, and group (Eth-SPH) received ethanol and sardinelle proteins hydrolysate simultaneously. All treatments were made by gavage during 15 d. Treatment with ethanol revealed a significant elevation of malondialdehyde and protein carbonyl levels in the heart and of aspartate transaminase and alanine transaminase activities in plasma. Nitric oxide levels and the activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase decreased. Nonenzymatic antioxidant such as reduced glutathione did not significantly change and ascorbic acid was decreased. SPH intake concomitantly with ethanol restored these parameters to near control values. These modifications confirmed histopathological aspects of the heart. The results revealed that SPH could provide protection of the myocardium against ethanol-induced oxidative damages in rats. This may be due to the high antioxidant potential of SPH. PMID- 22780572 TI - Toward an iron(II) spin-crossover grafted phosphazene polymer. AB - Two new cyclotriphosphazene ligands with pendant 2,2':6',2"-terpyridine (Terpy) moieties, namely, (pentaphenoxy){4-[2,6-bis(2 pyridyl)]pyridoxy}cyclotriphosphazene (L(1)), (pentaphenoxy){4-[2,6-terpyridin-4 yl]phenoxy}cyclotriphosphazene (L(2)), and their respective polymeric analogues, L(1P) and L(2P), were synthesized. These ligands were used to form iron(II) complexes with an Fe(II)Terpy(2) core. Variable-temperature resonance Raman, UV visible, and Mossbauer spectroscopies with magnetic measurements aided by density functional theory calculations were used to understand the physical characteristics of the complexes. By a comparison of measurements, the polymers were shown to behave in the same way as the cyclotriphosphazene analogues. The results showed that spin crossover (SCO) can be induced to start at high temperatures by extending the spacer length of the ligand to that in L(2) and L(2P); this combination provides a route to forming a malleable SCO material. PMID- 22780571 TI - Toward the total synthesis of palhinine A: expedient assembly of multifunctionalized isotwistane ring system with contiguous quaternary stereocenters. AB - The stereoselective, expedient assembly of the key functionalized isotwistane (bridged tricyclo[4.3.1.0(3,7)]decane) system, 5/6/6 ring, with contiguous quaternary stereocenters in Lycopodium alkaloid palhinine A and its analogues via an intramolecular Diels-Alder strategy is described. PMID- 22780564 TI - Impact of postprandial glycaemia on health and prevention of disease. AB - Postprandial glucose, together with related hyperinsulinemia and lipidaemia, has been implicated in the development of chronic metabolic diseases like obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In this review, available evidence is discussed on postprandial glucose in relation to body weight control, the development of oxidative stress, T2DM, and CVD and in maintaining optimal exercise and cognitive performance. There is mechanistic evidence linking postprandial glycaemia or glycaemic variability to the development of these conditions or in the impairment in cognitive and exercise performance. Nevertheless, postprandial glycaemia is interrelated with many other (risk) factors as well as to fasting glucose. In many studies, meal-related glycaemic response is not sufficiently characterized, or the methodology with respect to the description of food or meal composition, or the duration of the measurement of postprandial glycaemia is limited. It is evident that more randomized controlled dietary intervention trials using effective low vs. high glucose response diets are necessary in order to draw more definite conclusions on the role of postprandial glycaemia in relation to health and disease. Also of importance is the evaluation of the potential role of the time course of postprandial glycaemia. PMID- 22780574 TI - Current toxicological aspects on drug and chemical transport and metabolism across the human placental barrier. AB - INTRODUCTION: Placenta plays an obligatory role in fetal growth and development by performing a multitude of functions, including embryo implantation, transport of nutrients and elimination of metabolic waste products and endocrine activity. Drugs and chemicals can transfer across the placental barrier from mother to fetus either by passive diffusion mechanisms and/or via a network of active transporters, which may lead to potential fetotoxicity effects. Placenta also expresses a wide variety of enzymes, being capable of metabolizing a large diversity of drugs and chemicals to metabolites of lower or even higher toxicity than parent compounds. AREAS COVERED: The present review aims to summarize the current toxicological aspects in the emerging topic of drug transport and metabolism across the human placental barrier. EXPERT OPINION: There is an emerging demand for accurate assessment of drug transport and metabolism across the human placental barrier, on the basis of a high throughput screening process in the early stages of drug design, to avoid drug candidates from potential fetotoxicity effects. In this aspect, combined studies, which take into account in vivo and in vitro investigations, as well as the ex vivo perfusion method and the recently developed computer-aided technologies, may significantly contribute to this direction. PMID- 22780573 TI - Long-term clinical outcome of differentiated thyroid cancer patients with undetectable stimulated thyroglobulin level one year after initial treatment. AB - BACKGROUND: Measurement of the serum thyroglobulin (Tg) level with TSH stimulation (sTg) is the cornerstone of monitoring for the recurrence or persistence of differentiated thyroid cancer (DTC) in patients who have undergone surgery and remnant ablation. However, there have been several reports that an undetectable sTg could not predict the absence of future recurrence. The aim of this study was to evaluate the long-term outcome of DTC patients who achieved biochemical remission (BR, defined as sTg<1 ng/mL) after initial treatment, and to determine the role of repeated sTg measurement in detecting a clinical recurrence. METHODS: This is a retrospective observational cohort study in a tertiary referral hospital. There were 1010 DTC patients who achieved BR at 12 months after the initial treatment (surgery and ablation), and they were eligible for analysis. Among them, 787 patients had values of repeated sTg. RESULTS: Thirteen out of 1010 (1.3%) patients had clinical recurrences during a median 84 months of follow-up. All of the clinical recurrences were limited to the cervical lymph nodes without clinical evidence of distant metastasis. Among 787 patients with available repeated sTg, 10 had clinical recurrences (5 out of 750 patients with repeated sTg<1 ng/mL and 5 out of 37 patients with repeated sTg >= 1 ng/mL). Patients with repeated sTg >= 1 ng/mL had a much greater chance of disease recurrence (log-rank statistics=43.7, df=1, p<0.001). CONCLUSIONS: About 1% of DTC patients who had sTg<1 ng/mL 12 months after initial treatment had a clinical recurrence. All of clinical recurrences were loco-regional recurrences. Although repeated sTg measurement can be helpful to predict recurrence, we could not recommend it for surveillance in patients with BR due to its very low yield. PMID- 22780575 TI - The role of angiotensin II receptor 1 (AT1) blockade in cisplatin-induced nephrotoxicity in rats: gender-related differences. AB - It is documented that chronic renal diseases are gender related. The protective role of angiotensin II receptor 1 (AT1) blocker losartan against cisplatin (CP) induced nephrotoxicity was reported in males, but the role of gender is not well known. Six groups of Wistar rats were studied. Rats were divided into two groups of males and females to receive losartan for 9 days plus a single dose of CP (7 mg/kg) at day 3. Two positive control groups of males and females received the same regimen, except that they received saline instead of losartan. The negative control groups received saline instead of CP at day 3 and also saline instead of losartan. The blood samples were obtained, and the kidneys underwent histopathological investigations. All the CP-treated animals lost weight, but losartan promoted weight loss in females (p < 0.05). Coadministration of losartan and CP in females, but not in males, significantly increased the serum levels of blood urea nitrogen and creatinine when compared with the negative and positive control groups (p < 0.05). No significant differences were observed in serum levels of total proteins, magnesium, and nitrite between the groups. Administration of CP increased the kidney tissue damage score (KTDS) and normalized kidney weight (p < 0.05). However, in the presence of AT1 blockade, the KTDS (nonsignificantly) and normalized kidney weight (significantly, p < 0.05) increased in the CP-treated females. Such an observation was not seen in males. Losartan may prevent CP-induced nephrotoxicity in males, but it promotes the CP-induced damage in females, which may be related to the renin-angiotensin system receptors in the kidneys. PMID- 22780576 TI - Intralymphatic granulomas in lymphoedema secondary to anogenital granulomatosis. AB - The granulomatous inflammation seen in filariasis, orofacial granulomatosis (OFG), rosacea and sarcoidosis can be associated with lymphoedema. In the setting of OFG, the finding of intralymphatic granulomas has been reported as a possible mechanism for lymphoedema. Anogenital granulomatosis (AGG) is a similar chronic inflammatory condition of unknown pathogenesis. It presents as granulomatous genital or anoperineal inflammation and associated lymphoedema, with histological findings of non-caseating granulomas and a perivascular infiltrate. We report a case of AGG and lymphoedema with intralymphatic granulomas seen on biopsy. This finding is unique and we propose that the intralymphatic granulomatous inflammation causes a partial or complete occlusion of lymphatic drainage, thus resulting in the clinical situation of lymphoedema. PMID- 22780577 TI - Preterm neonatal cardiovascular instability: does understanding the fetus help evaluate the newborn? AB - Preterm newborns, particularly very low birth weight newborns, frequently experience intermittent hypotension and/or hypoperfusion. Organ perfusion is largely distinct from systemic hypotension, suggesting that changes in underlying vascular tone are the major determinants of perfusion. Preterm fetuses have a remarkable anaerobic tolerance and ability to survive major insults with no or limited injury, balanced by relative immaturity of key autonomic responses. Exposure to hypoxia-ischaemia and infection trigger complex changes in vascular tone that evolve over many days and there is evidence that these are centrally controlled and linked, in part, with underlying organ metabolism. Hypoperfusion frequently occurs after hypoxia-ischaemia without organ injury occurring. Hypoxia ischaemia, infection and many clinical interventions, such as steroid therapy and ventilation, can interact to increase or decrease the risk of brain injury. PMID- 22780578 TI - Diastereoselective synthesis of seven-membered-ring trans-alkenes from dienes and aldehydes by silylene transfer. AB - Silver-catalyzed silylene transfer to alkenes forms vinylsilacyclopropanes regioselectively. These allylic silanes undergo additions to aldehydes to form seven-membered-ring trans-alkenes with high diastereoselectivity. The high reactivity of the trans-alkenes is evidenced by their formal [1,3]-sigmatropic rearrangement reactions and the rapid additions of oxygen-hydrogen bonds across the carbon-carbon double bonds. PMID- 22780579 TI - Health professionals' attitudes toward older people and older patients: a systematic review. AB - Attitudes toward older people and older patients among healthcare professionals are of concern throughout the world, but there are no recent systematic reviews which have examined and compared the attitudes across the various healthcare professionals who provide healthcare to older people. A comprehensive literature search (2000-2011) was undertaken on electronic databases (CINAHL, MEDLINE, EMBASE, British Nursing Index, PsycINFO, Chinese Biomedical database, China Medical Academic Conference and China Academic Journal) using a combination of terms. We identified 2179 articles indexed with these terms. Initial screening was undertaken by two researchers and then checked by a third researcher. In total, the reviewers selected 117 articles which, on the basis of their abstracts, appeared to meet the criteria for inclusion. We obtained the full texts and two reviewers assessed each full text paper to further examine whether it met all the criteria. The final review identified 51 studies. Publications over the last 10 years show that attitudes towards older people and older patients range from neutral to positive among healthcare professionals and highlight the need for well-designed studies of both qualified and student healthcare professionals recruiting random samples across multiple sites and utilizing validated instruments consistently to permit comparison over time and across countries. PMID- 22780580 TI - Dramatic weight loss with rufinamide. AB - Rufinamide (RUF) is a novel antiepileptic drug considered as second-line therapy in the treatment of Lennox-Gastaut syndrome. Treatment-emergent adverse events (AEs) have consisted mainly of drowsiness, irritability, vomiting, and loss of appetite. RUF is considered as a "weight-neutral" drug. We found clinically significant weight loss in 7 of 15 consecutive adult patients (47%; 3 male, 4 female, aged 18-31 years) treated with RUF as add-on therapy (800-2,400 mg/day: 23.5-57.1 mg/kg/day). The body mass index (BMI) decreased by 7.3-18.7%. Two patients were obese class I before RUF. Five patients (71%) were underweight before RUF (mild in one case, moderate in two cases, and severe in two cases). Four of these patients stopped RUF because of this adverse effect. RUF was recommenced in two patients using a lower and slower dosing strategy; one patient showed improvement in seizure control and no weight loss but RUF was re-stopped in the second patient because of continued weight loss. Despite of weight loss, RUF was continued in two other patients because it reduced seizure activity. We primarily related weight loss to reduced food intake, that is, loss of appetite and nausea, although in two patients no obvious loss of appetite was reported. RUF can cause clinically significant weight loss in adult patients, even at low dose. This AE can affect patients who are already underweight. There is a possibility that lower starting doses and slower escalation might minimize weight loss, but further information is required to determine whether this is the case. PMID- 22780581 TI - Stepwise Diels-Alder: more than just an oddity? A computational mechanistic study. AB - We have employed hybrid DFT and SCS-MP2 calculations at the SMD-PCM-6 311++G(2d,2p)//6-31+G(d) level to investigate the relationship between three possible channels for forming a Diels-Alder adduct from a highly nucleophilic diene and moderately to highly electrophilic dienophiles. We discuss geometries optimized using the B3LYP and M06-2X functionals with the 6-31+(d) basis set. The transition states and intermediates are characterized on the basis of geometric and electronic properties, and we also address the possibility of predicting detectability of a zwitterionic intermediate based on its relative stability. Our results show that a conventional Diels-Alder transition state conformation yields intermediates in all four investigated cases, but that these are too short-lived to be detected experimentally for the less activated reactants. The stepwise trans pathway, beginning with a conjugate addition-like transition state, becomes increasingly competitive with more activated reactants and is indeed favored for the most electrophilic dienophiles. Addition of a trans diene leads to a dead-end as the trans intermediates have insurmountable rotation barriers that prohibit formation of the second bond, unless another, heterocyclic intermediate is formed. We also show that introduction of a hydrogen bond donating catalyst favors a stepwise pathway even for less activated dienophiles. PMID- 22780582 TI - Acutely induced anxiety increases negative interpretations of events in a closed circuit television monitoring task. AB - In two experiments we measured the effects of 7.5% CO2 inhalation on the interpretation of video footage recorded on closed circuit television (CCTV). As predicted, inhalation of 7.5% CO2 was associated with increases in physiological and subjective correlates of anxiety compared with inhalation of medical air (placebo). Importantly, when in the 7.5% CO2 condition, participants reported the increased presence of suspicious activity compared with placebo (Experiment 1), a finding that was replicated and extended (Experiment 2) with no concomitant increase in the reporting of the presence of positive activity. These findings support previous work on interpretative bias in anxiety but are novel in terms of how the anxiety was elicited, the nature of the interpretative bias, and the ecological validity of the task. PMID- 22780583 TI - Sharpening and formation: two distinct neuronal mechanisms of repetition priming. AB - The repetition of an object stimulus results in faster and better recognition of this object (repetition priming). This phenomenon is neuronally associated with a reduced firing rate of neurons (repetition suppression). It has been interpreted as a sharpening mechanism within the cell assembly representing the object. In the case of an unfamiliar stimulus for which no object representation exists, the repetition of the stimulus results in an increase in the firing rate (repetition enhancement).It has been hypothesized that this increase reflects the formation of a cortical object representation. We aimed to investigate cortical object representations as well as repetition suppression and enhancement by means of the steady-state visual evoked potential (SSVEP) in the healthy human brain. To that end, we used a repetition paradigm with familiar and unfamiliar objects, each presented with 12-Hz flicker, producing an oscillatory brain response at the same frequency (i.e. an SSVEP). Results showed significantly smaller SSVEP amplitudes for repeated familiar objects compared to their first presentation (repetition suppression). For unfamiliar objects, SSVEP amplitudes increased with stimulus repetition (repetition enhancement). Source reconstruction revealed inferior temporal regions as generators for the repetition suppression effect, probably reflecting a sharpening mechanism within the cortical representations of the constituting features of an object. In contrast, repetition enhancement was localised in the superior parietal lobe, possibly reflecting the formation of a structural object representation. Thus, the mechanisms underlying repetition priming (i.e. sharpening and formation) depend on the semantic content of the incoming information. PMID- 22780584 TI - RNase Y of Staphylococcus aureus and its role in the activation of virulence genes. AB - RNase Y of Bacillus subtilis is a key member of the degradosome and important for bulk mRNA turnover. In contrast to B. subtilis, the RNase Y homologue (rny/cvfA) of Staphylococcus aureus is not essential for growth. Here we found that RNase Y plays a major role in virulence gene regulation. Accordingly, rny deletion mutants demonstrated impaired virulence in a murine bacteraemia model. RNase Y is important for the processing and stabilization of the immature transcript of the global virulence regulator system SaePQRS. Moreover, RNase Y is involved in the activation of virulence gene expression at the promoter level. This control is independent of both the virulence regulator agr and the saePQRS processing and may be mediated by small RNAs some of which were shown to be degraded by RNase Y. Besides this regulatory effect, mRNA levels of several operons were significantly increased in the rny mutant and the half-life of one of these operons was shown to be extremely extended. However, the half-life of many mRNA species was not significantly altered. Thus, RNase Y in S. aureus influences mRNA expression in a tightly controlled regulatory manner and is essential for coordinated activation of virulence genes. PMID- 22780585 TI - Term MRI for small preterm babies: do parents really want to know and why has nobody asked them? PMID- 22780683 TI - Enantioselective conjugate addition of donor-acceptor hydrazones to alpha,beta unsaturated aldehydes through formal diaza-ene reaction: access to 1,4-dicarbonyl compounds. AB - Donor-acceptor monosubstituted hydrazones participate as suitable reagents able to undergo an enantioselective formal diaza-ene reaction with alpha,beta unsaturated aldehydes under chiral secondary amine catalysis. This constitutes a new approach for the enantioselective conjugate addition of hydrazones to enals under metal-free conditions and leads to the formation of gamma-hydrazono carboxylic acids after oxidation/[1,3]-H shift. The methodology is also useful for the synthesis of enantioenriched beta-substituted alpha-keto-1,5-diesters by using the hydrazone moiety as a masked carbonyl group. PMID- 22780684 TI - Molecular dynamics simulations to provide new insights into the asymmetrical ammonium ion movement inside of the [d(G3T4G4)]2 G-quadruplex DNA structure. AB - We have used both adaptive biasing force (ABF) and regular molecular dynamics (MD) simulations to investigate the asymmetrical NH(4)(+) ion movement inside of a bimolecular G-quadruplex DNA structure [d(G(3)T(4)G(4))](2). The free-energy landscapes obtained from ABF MD simulations suggest that the NH(4)(+) ion exiting the [d(G(3)T(4)G(4))](2) G-quadruplex stem in the direction toward the edge-type loop (denoted as the upper direction) experiences a lower free-energy barrier than that toward the diagonal loop (denoted as the lower direction) by approximately 3-4 kcal mol(-1). This result is in qualitative agreement with the previous discovery made by Sket and Plavec on the same G-quadruplex structure from (15)N NMR experiments (J. Am. Chem. Soc. 2007, 129, 8794). In the Na(+) form of the same G-quadruplex, Na(+) ion movement was found to be symmetrical, with a free-energy barrier of only 5-7 kcal mol(-1) to cross all three G-quartets, that is, [d(G(3)T(4)G(4))](2) still exhibits ion-channel-like behaviors for Na(+) ions. On the basis of the new computational results, we hypothesize that the stiffness of a G-quartet is primarily determined by the base stacking interactions within the G-quadruplex stem. Therefore, the structural origin for the asymmetrical NH(4)(+) ion movement in [d(G(3)T(4)G(4))](2) is the presence of two different modes of base stacking around the NH(4)(+) binding sites, a more stable 5'-syn-anti mode between lower and central G-quartets and a less stable 5' anti-anti mode between upper and central G-quartets. Simulations also suggest that loop topology at the end of a G-quadruplex stem only controls the direction at which an exiting NH(4)(+) ion reaches bulk solution but does not impose significant free-energy barriers. PMID- 22780685 TI - Efficient pseudo-enantiomeric carbohydrate olefin ligands. AB - Highly efficient pseudo-enantiomeric olefin ligands were designed from D-glucose and D-galactose. These ligands yield consistently excellent levels of enantioselectivity in Rh(I)-catalyzed 1,4-additions of aryl- and alkenylboronic acids to achiral enones and high diastereoselectivity with chiral substrates. Contrary to established olefin ligands, they are obtained enantiomerically pure via short syntheses without racemic resolution steps, making them a valuable addition to the arsenal of chiral ligands with olefinic donor sites. PMID- 22780686 TI - Pharmacodynamics of ginsenosides: antioxidant activities, activation of Nrf2, and potential synergistic effects of combinations. AB - Ginseng has long been used in Asian countries for more than 2000 years. Currently, in the "Western World or Western Medicines", many reports have indicated that they have used herbal medicines, and ginseng is one of the most popular herbs. Several recent reports have indicated that the antioxidant/antioxidative stress activities of ginseng play a role in the benefits of ginseng; however, the precise mechanism is lacking. The antioxidant response element (ARE) is a critical regulatory element for the expression of many antioxidant enzymes and phase II/III drug metabolizing/transporter genes, mediated by the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The aim of this study was to examine the potential activation and synergism of Nrf2-ARE-mediated transcriptional activity between three common ginsenosides present in ginseng, ginsenoside Rb1 (Rb1), ginsenoside Rg1 (Rg1), and ginsenoside 20(S)-protopanaxatriol (20S). We tested whether these ginsenosides and their combinations could induce Nrf2-ARE activities in HepG2-C8 cells with stably transfected ARE luciferase reporter gene. Cell proliferation, antioxidant and ARE activities, Western blotting of Nrf2 protein, and qPCR of mRNA of Nrf2 were conducted for Rb1, Rg1, and 20S as well as the combinations of 20S with Rb1 or Rg1. To determine the combination effects, the combination index (CI) was calculated. Rb1 and Rg1 are relatively nontoxic to the cells, while 20S at 50 MUM or above significantly inhibited the cell proliferation. Rb1, Rg1, or 20S induced total antioxidant activity and ARE activity in a concentration dependent manner. Furthermore, combinations of 20S with either Rb1 or Rg1 induced total antioxidant and ARE activity synergistically. The induction of Nrf2 protein and mRNA was also found to be synergistic with the combination treatments. In summary, in this study, we show that ginsenosides Rb1, Rg1, and 20S possess antioxidant activity, transcriptionally activating ARE as well as the potential of synergistic activities. The Nrf2-ARE-mediated antioxidant pathway could play a role for the overall antioxidative stress activities, which could be important for ginseng's health beneficial effects such as cancer chemopreventive activities. PMID- 22780688 TI - HIV testing and re-engagement for individuals with previously diagnosed HIV Infection in New Orleans, Louisiana. PMID- 22780687 TI - Hydrogel particles as a particulate stabilizer for dispersion polymerization. AB - Hydrogel particles composed of poly(N-isopropylacrylamide) were used as a particulate steric stabilizer for the dispersion polymerization of styrene for the first time. The effects of the size and concentration of the hydrogel particles on the resultant polystyrene particles were investigated. As expected, the hydrogel particles indeed play the role of steric stabilizer for dispersion polymerization. Moreover, some of the resultant polystyrene particles were covered with hydrogel particles, which was confirmed by electron microscopy and X ray photoelectron spectroscopy. PMID- 22780689 TI - Chlorine/methyl exchange reactions in silylated aminostibanes: a new route to stibinostibonium cations. AB - The Lewis acid assisted triflate/methyl, azide/methyl, and chlorine/methyl exchange reactions between silicon and antimony have been studied in the reaction of R(Me(3)Si)N-SbCl(2) (R = Ter) with AgOTf, AgN(3), KOtBu, GaCl(3), and Me(3)SiN(3)/GaCl(3), resulting in the formation of different methylantimony compounds. Furthermore, R(Me(3)Si)N-SbCl(2) (R = SiMe(3)) was reacted with GaCl(3) at low temperatures to yield a hitherto unreported amino(chloro)stibenium cation, the proposed intermediate in methyl exchange reactions. Tetrachloridogallate salts bearing different stibinostibonium cations such as [(Me(3)Sb)SbMe(2)](+) and [(Me(3)Sb)(2)SbMe](2+) along with the GaCl(3) adduct of SbMe(3) were isolated from such R(Me(3)Si)N-SbCl(2)/GaCl(3) mixtures (R = SiMe(3)) at ambient temperatures, depending on the reaction parameters. PMID- 22780690 TI - Effects of Polycan, a beta-glucan, on experimental periodontitis and alveolar bone loss in Sprague-Dawley rats. AB - BACKGROUND AND OBJECTIVE: Polycan is a promising candidate for the treatment of periodontal disease. This study was undertaken to examine whether Polycan, a type of beta-glucan, has a protective effect on ligature-induced experimental periodontitis and related alveolar bone loss in Sprague-Dawley rats. MATERIAL AND METHODS: Polycan was orally administered, daily, for 10 d, at 21.25, 42.5 or 85 mg/kg, beginning 1 d after ligation. Changes in body weight and alveolar bone loss were monitored, and the anti-inflammatory effects of Polycan were determined by measuring the levels of myeloperoxidase (MPO), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in gingival tissue. We also evaluated inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA) concentrations as a measure of the antioxidant effect. RESULTS: Ligature placement led to a marked decrease in body weight, increased alveolar bone loss and increased concentrations of MPO, IL-1beta, TNF-alpha and MDA, as well as increased iNOS activity and inflammatory cell infiltration and decreased collagen fiber content. Histological examination revealed increases in the number and activity of osteoclast cells, decreases in alveolar bone volume and elevated percentages of osteclasts on the alveolar bone surface. Daily oral treatment with 42.5 or 85 mg/kg of Polycan for 10 d led to significant, dose-dependent inhibition of the effect of ligature placement. CONCLUSION: Taken together, these results suggest that 10 d of oral treatment with Polycan effectively inhibits ligature placement-induced periodontitis and related alveolar bone loss via an antioxidant effect. PMID- 22780691 TI - Computational lateral flow biosensor for proteins and small molecules: a new class of strip logic gates. AB - The first example of strip logic gates ("OR" and "AND" functions) for proteins and small molecules has been constructed on the basis of target-induced self assembly of split aptamer fragments. Using thrombin and ATP as inputs, the corresponding split/integrated aptamers as molecular recognition elements, and gold nanoparticles as a tracer, the output signals can be directly visualized by observing the red bands on the test zones of the strips. The assay is simple, easy to perform, and cost-effective, allowing portable analysis at ambient temperature. The strip logic system is resistant to nonspecific interfering agents and can operate effectively even in human serum samples. Such logic strips hold great promise for application in intelligent point-of-care and in-field diagnostics. PMID- 22780692 TI - Cardiovascular disease in chronic kidney disease: untying the Gordian knot. AB - Chronic kidney disease (CKD) affects around 10-13% of the general population, with only a small proportion in end stage renal disease (ESRD), either on dialysis or awaiting renal transplantation. It is well documented that CKD patients have an extremely high risk of developing cardiovascular disease (CVD) compared with the general population, so much so that in the early stages of CKD patients are more likely to develop CVD than they are to progress to ESRD. Various pathophysiological pathways and explanations have been advanced and suggested to account for this, including endothelial dysfunction, dyslipidaemia, inflammation, left ventricular hypertrophy and cardiac autonomic dysfunction. In this review, we try to understand and further explore the link between CKD and CVD, as well as offering interventional advice where available, while exposing the current lack of RCT-based research and trial evidence in this area. We also suggest pragmatic Interim measures we could take while we wait for definitive RCTs. PMID- 22780696 TI - Acute alveolitis following infliximab therapy for psoriasis. AB - Infliximab is a high-affinity recombinant chimeric immunoglobulin-1 monoclonal antibody directed against tumour necrosis factor-alpha. It is used to treat a range of inflammatory disorders including psoriatic joint and skin changes. Acute interstitial lung disease is a rare but potentially fatal complication of therapy. We report the case of a 67-year-old man with severe psoriasis who presented with acute alveolitis shortly after his third infusion of infliximab. The infliximab was discontinued and investigations did not reveal an infective cause. His respiratory signs and symptoms improved quickly with corticosteroid therapy. Clinicians should be aware of this uncommon but potentially serious complication. PMID- 22780697 TI - Inclusion compound based approach to arrays of artificial dipolar molecular rotors: bulk inclusions. AB - We examine the insertion of two dipolar molecular rotors as guests into a host, tris(o-phenylenedioxy)cyclotriphosphazine (TPP, 1), using differential scanning calorimetry, solid-state NMR, powder X-ray diffraction, and dielectric spectroscopy. The rotors are 1-(4'-n-pentylbiphenyl-4-yl)-12-(2,3-dichlorophenyl) p-dicarba-closo-dodecaborane and 1,12-bis(2,3-dichlorophenyl)-p-dicarba-closo dodecaborane. Both enter the bulk even though their nominal diameter exceeds the nominal channel diameter and although a closely related rotor, 1-n-hexadecyl-12 (2,3-dichlorophenyl)-p-dicarba-closo-dodecaborane, is known to produce a surface inclusion compound. Rotational barriers of 5.4-9.3 kcal/mol were found for the dichlorophenyl rotator contained within the TPP channel. Clearly, van der Waals diameters in themselves do not suffice to predict TPP channel entry. It is suggested that the efficacy of the p-carborane stopper is reduced by the presence of the two relatively bulky adjacent benzene rings, which help to stretch the channel, and by the axial direction of its axis, which prevents the attached rotator from contributing to the stopping action. PMID- 22780699 TI - Dissecting the genetic basis of myoclonic-astatic epilepsy. AB - Herman Doose first described the generalized childhood epilepsy syndrome of myoclonic astatic epilepsy (MAE) in 1970, attributing a genetic cause from this first description. However, although the International League Against Epilepsy (ILAE) defined criteria for MAE in 1989, the diagnostic boundaries of the syndrome continue to be debated. Moreover, 40 years since Doose's first description of MAE, although a genetic predisposition is acknowledged and many studies have demonstrated familial aggregation of seizures within MAE families, the actual genetic determinants of MAE still remain unknown. Although initially thought to be within the same spectrum as severe myoclonic epilepsy of infancy, the exclusion of SCN1A mutations in non-generalized epilepsy with febrile seizures plus (GEFS+) MAE cases has confirmed the genetic distinction of MAE. In this critical review, we shall trace the historical evolution of concepts around MAE and its distinction from Lennox-Gastaut syndrome, review the described phenotypic features of MAE from updated studies that will allow its distinction from other overlap epilepsy syndromes, review the evidence of genetic influences and clues for genetic heterogeneity, and discuss strategies that may be helpful in elucidating the etiology of MAE in light of current genetic techniques. PMID- 22780698 TI - Dynamics of anticipatory mechanisms during predictive context processing. AB - We employed an electroencephalography paradigm manipulating predictive context to dissociate the neural dynamics of anticipatory mechanisms. Subjects either detected random targets or targets preceded by a predictive sequence of three distinct stimuli. The last stimulus in the three-stimulus sequence (decisive stimulus) did not require any motor response but 100% predicted a subsequent target event. We showed that predictive context optimises target processing via the deployment of distinct anticipatory mechanisms at different times of the predictive sequence. Prior to the occurrence of the decisive stimulus, enhanced attentional preparation was manifested by reductions in the alpha oscillatory activities over the visual cortices, resulting in facilitation of processing of the decisive stimulus. Conversely, the subsequent 100% predictable target event did not reveal the deployment of attentional preparation in the visual cortices, but elicited enhanced motor preparation mechanisms, indexed by an increased contingent negative variation and reduced mu oscillatory activities over the motor cortices before movement onset. The present results provide evidence that anticipation operates via different attentional and motor preparation mechanisms by selectively pre-activating task-dependent brain areas as the predictability gradually increases. PMID- 22780700 TI - A few thoughts on evidence in social work. AB - Social work practitioners must act every working day in the face of uncertainty. This uncertainty arises in part because knowledge is often difficult to locate or sometimes lacking regarding: the systems context the population being served; the particular client system; the set of problems the client system is experiencing; as well as the various interventions that could be selected. It seems reasonable to explore ways to reduce the experience of uncertainty, and narrow, if not eliminate, the knowledge gaps that arise in such situations. The generic idea of evidence-based practice has been advanced for some time as an approach to support practitioners in their day-to-day work. This article has two foci. First, it will briefly and selectively review attempts to make social work practice more evidence based. Second, it will describe one stage in the evolution of a Web based service (information for practice [IP]). IP is a long-term project with the mission of keeping practitioners informed about news and new scholarship in the field, so that they can more easily make their practice more evidenced based. PMID- 22780701 TI - Factors associated with health care access and outcome. AB - This study aims to (1) assess ethnic differences in health care access and health outcome between Asian Americans and whites and between Asian American subgroups, (2) examine effects of cultural factors, and (3) investigate moderating effects of health risk behaviors between cultural characteristics and health care access and outcome. Data were derived from the 2007 California Health Interview Survey. Asian Americans (n = 4,462) and whites (n = 4,470) were included. There were significant ethnic differences in health care access and health perception between Asian Americans and Whites and across Asian American subgroups. Health risk behaviors moderated relationships between cultural factors and health care access and outcome. Findings reveal that ethnicity affects an individual's health care access and health perception, and their health behaviors are an important factor that may improve or worsen outcomes. This study may increase our knowledge base of research and interventions to enhance ethnic minority populations' health care accessibility and perceptions. PMID- 22780702 TI - "We don't have a back-up plan": an exploration of family contingency planning for emergencies following stroke. AB - Little research has explored emergency preparedness among families coping with stroke. In this longitudinal qualitative study, we explored contingency caregiving planning by interviewing (N = 18) family caregivers providing care for a stroke survivor at home during the first 6 months post-discharge from the hospital. Emergent themes showed most families did not have a concrete "back-up plan" for a crisis or disaster situation involving the primary caregiver being unable to provide care. Furthermore, they assumed formal respite services or long term care would be available should the need arise. Despite increased awareness over time, most caregivers had not devised contingency plans at 6 months. PMID- 22780703 TI - Adolescent mothers' subjective well-being and mothering challenges in a Yoruba community, southwest Nigeria. AB - Well-being varies within cultures and context. Studies on the well-being and mothering challenges of adolescents in Nigeria have focused on the general poor well-being of adolescent mothers rather than exploring their agency and subjective well-being within specific context. This study explores adolescent mothers' (13-20 years) subjective well-being by focusing on their childbirth, mothering experiences, and available network of supports. Thirty face-to-face in depth interviews were conducted through the support of four informants and peer referrals. Content analysis was used to identify salient themes and patterns. Findings showed that a high proportion of the adolescent mothers had stigmatizing experiences among which include dropping out of school, and lack of supports from families, friends, and the society. Where available, supports were perceived as inadequate in contributing to their well-being and that of their children. Some of the adolescent mothers were apprehensive of losing their children to ill health while emphasizing that their present challenges could affect their children's future. However, the adolescent mothers invoked their agency by subtly using strategies such as petty trading and apprenticeship to reduce the social consequences of unintended pregnancy and earn a living. Recognizing adolescent mothers' agency in policies targeted toward their empowerment would be of benefit. PMID- 22780705 TI - Blood pressure as a drug target: what should we be measuring? PMID- 22780707 TI - Adherence, persistence, healthcare utilization, and cost benefits of guideline recommended hepatitis B pharmacotherapy. AB - OBJECTIVE: To compare pharmacotherapy adherence, persistence, and healthcare utilization/costs among US patients with chronic hepatitis B (CHB) initiated on an oral antiviral monotherapy recommended as first-line treatment by current national (US) guidelines vs an oral antiviral not recommended as first-line monotherapy. RESEARCH DESIGN AND METHODS: In this retrospective cohort study, patients aged 18-64 with medical claims for CHB who initiated an oral antiviral monotherapy for CHB between 07/01/05 and 01/31/10 were identified from a large US commercial health insurance claims database. Patients were continuously enrolled for a 6-month baseline period and >=90 days follow-up. They were assigned to 'currently recommended first-line therapy' (RT: entecavir or tenofovir) or 'not currently recommended first-line therapy' (NRT: lamivudine, telbivudine, or adefovir) cohorts. MAIN OUTCOME MEASURES: Multivariate analyses were conducted to compare treatment adherence, persistence, healthcare utilization, and costs for RT vs NRT cohorts. RESULTS: Baseline characteristics were similar between RT (n=825) and NRT (n=916) cohorts. In multivariate analyses, RT patients were twice as likely as NRT patients to be adherent (OR=2.09; p<0.01) and persistent (mean: RT=361 days, NRT=298 days; p<0.01) and half as likely to have an inpatient stay (OR=0.527; p<0.01). Between the two oral antivirals recommended as first-line treatment, even though pharmacy cost was higher for entecavir, mean total healthcare costs for entecavir and tenofovir were similar ($1214 and $1332 per patient per month, respectively). Similar results were also observed with regard to adherence, persistence, and healthcare use for entecavir and tenofovir. CONCLUSIONS: A limitation associated with analysis of administrative claims data is that coding errors can be mitigated but are typically not fully eradicated by careful study design. Nevertheless, the current findings clearly indicate the benefits of initiating CHB treatment with an oral antiviral monotherapy recommended as first-line treatment by current guidelines. PMID- 22780708 TI - "Real-time" disintegration analysis and D-optimal experimental design for the optimization of diclofenac sodium fast-dissolving films. AB - The objective of this work was to study the dissolution and mechanical properties of fast-dissolving films prepared from a tertiary mixture of pullulan, polyvinylpyrrolidone and hypromellose. Disintegration studies were performed in real-time by probe spectroscopy to detect the onset of film disintegration. Tensile strength and elastic modulus of the films were measured by texture analysis. Disintegration time of the films ranged from 21 to 105 seconds whereas their mechanical properties ranged from approximately 2 to 49 MPa for tensile strength and 1 to 21 MPa% for young's modulus. After generating polynomial models correlating the variables using a D-Optimal mixture design, an optimal formulation with desired responses was proposed by the statistical package. For validation, a new film formulation loaded with diclofenac sodium based on the optimized composition was prepared and tested for dissolution and tensile strength. Dissolution of the optimized film was found to commence almost immediately with 50% of the drug released within one minute. Tensile strength and young's modulus of the film were 11.21 MPa and 6, 78 MPa%, respectively. Real time spectroscopy in conjunction with statistical design were shown to be very efficient for the optimization and development of non-conventional intraoral delivery system such as fast dissolving films. PMID- 22780709 TI - Conformational effect on energy transfer in single polythiophene chains. AB - Herein we describe the use of regioregular (rr-) and regiorandom (rra-) P3HT as models to study energy transfer in ordered and disordered single conjugated polymer chains. Single molecule fluorescence spectra and excitation/emission polarization measurements were compared with a Forster resonance energy transfer (FRET) model simulation. An increase in the mean single chain polarization anisotropy from excitation to emission was observed for both rr- and rra-P3HT. The peak emission wavelengths of rr-P3HT were at substantially lower energies than those of rra-P3HT. A simulation based on FRET in single polymer chain conformations successfully reproduced the experimental observations. These studies showed that ordered conformations facilitated efficient energy transfer to a small number of low-energy sites compared to disordered conformations. As a result, the histograms of spectral peak wavelengths for ordered conformations were centered at much lower energies than those obtained for disordered conformations. Collectively, these experimental and simulated results provide the basis for quantitatively describing energy transfer in an important class of conjugated polymers commonly used in a variety of organic electronics applications. PMID- 22780710 TI - Rhodium-catalyzed acyl-transfer reaction between benzyl ketones and thioesters: synthesis of unsymmetric ketones by ketone CO-C bond cleavage and intermolecular rearrangement. AB - In the presence of catalytic amounts of RhH(CO)(PPh3)3 and 1,2 bis(diphenylphosphino)benzene (dppBz), acyl groups were transferred between benzyl ketones and thioesters/aryl esters. The rhodium complex catalyzed the cleavage of ketone CO-C bonds and intermolecular rearrangement giving unsymmetric ketones. The acyl-transfer reaction also occurred with 1-(p-chlorophenyl)-3-(p cyanophenyl)propane-2-one giving unsymmetric ketones. PMID- 22780711 TI - The relationship between apelin and parathyroid hormone in hemodialysis patients. AB - Both apelin and parathyroid hormone (PTH) are endogenous ligands for G-protein coupled receptors. Apelin acts as a mitogenic agent for osteoblasts, and metabolic bone abnormalities are frequently seen in hemodialysis (HD) patients because of hyperparathyroidism. The aim of this study was to analyze plasma apelin levels in HD patients and to determine whether they are related to PTH concentrations. A total of 23 HD patients [15 men and 8 women, with a mean (SD) age of 54.2 (4.4) years and a mean body mass index (BMI) of 25.0 (4.1) kg/m(2)] were studied and compared with 15 healthy subjects [6 men and 9 women, with a mean (SD) age of 51.3 (13.6) years and a BMI of 27.0 (4.3) kg/m(2)]. Plasma apelin-36 was measured using an enzyme immunometric assay method and PTH was measured by ELISA. There was no significant difference in apelin levels between the patients [0.80 (0.6) ng/mL] and the healthy subjects [0.83 (0.23) ng/mL]. There was a positive correlation between apelin and PTH (r = 0.66, p = 0.0001). The patients with PTH >300 pg/mL had significantly higher plasma apelin levels [1.17 (0.7) ng/mL] compared with the patients with PTH <300 pg/mL [0.50 (0.15) ng/mL] (p = 0.003). In conclusion, HD patients with secondary hyperparathyroidism have high plasma apelin levels, which suggest that apelin may protect bone in HD patients by acting as an osteoblastic factor. PMID- 22780712 TI - De novo asymmetric synthesis of all-D-, all-L-, and D-/L-oligosaccharides using atom-less protecting groups. AB - Oligosaccharide synthesis is hindered by the need for multiple steps as well as numerous selective protections and deprotections. Herein we report a highly efficient de novo route to various oligosaccharide motifs, of use for biological and medicinal structure activity studies. The key to the overall efficiency is the judicious use of asymmetric catalysis and synthetic design. These green principles include the bidirectional use of highly stereoselective catalysis (Pd(0)-catalyzed glycosylation/post-glycosylation). In addition, the chemoselective use of C-C and C-O pi-bond functionality, as atom-less protecting groups as well as an anomeric directing group (via a Pd-pi-allyl), highlights the atom-economical aspects of the route to a divergent set of natural and unnatural oligosaccharides (i.e., various d-/l-diastereomers of oligosaccharides as well as deoxysugars which lack C-2 anomeric directing groups). For example, in only 12 steps, the construction of a highly branched heptasaccharide with 35 stereocenters was accomplished from an achiral acylfuran. PMID- 22780814 TI - Prevalence of chronic kidney disease in patients undergoing cardiac rhythm device removal. AB - Cardiac implantable electronic device (CIED) leads can cause central venous stenosis (CVS). In addition, these devices can get infected. Both are critically important considerations in patients with chronic kidney disease (CKD) for at least two reasons: (i) central veins serve as the final pathway should these patients need an arteriovenous access to provide dialysis therapy; and (ii) the presence of renal failure increases the risk of CIED infection. In this analysis, we investigated the prevalence as well as the degree of chronic kidney disease in patients harboring a CIED. Patients undergoing CIED removal were evaluated from 2001 to 2011. The patients were categorized into CKD stage I-V based on National Kidney Foundation-Dialysis Outcomes Quality Initiative guidelines. A total of 503 patients underwent CIED removal. Demographic characteristics revealed that 30% had hypertension, 44% were diabetics, 77% had coronary artery disease, and 84% suffered from congestive heart failure. Ninety percent (452/503) of the patients had CKD (stage I = I9 [4.2%], stage II = 189 [41.8%], stage III A = 96 [21.2%], stage III B = 59 [13.0%], stage IV = 45 [9.9%], and stage V = 44 [9.7%]). Overall, 148 (32.7%) patients (stage III B, stage IV, and stage V) of 452 had advanced renal failure. The results of this study reveal that one-third of CIED patients undergoing device removal have advanced chronic kidney disease. PMID- 22780815 TI - Reversible light switch for macrocycle mobility in a DNA rotaxane. AB - A recent trend in DNA nanotechnology consists of the assembly of architectures with dynamic properties that can be regulated by employing external stimuli. Reversible processes are important for implementing molecular motion into DNA architectures as they allow for the regeneration of the original state. Here we describe two different approaches for the reversible switching of a double stranded DNA rotaxane architecture from a stationary pseudorotaxane mode into a state with movable components. Both states only marginally differ in their respective topologies but their mechanical properties are fundamentally different. In the two approaches, the switching operation is based on strand displacement reactions. One of them employs toehold-extended oligodeoxynucleotides whereas in the other one the switching is achieved by light irradiation. In both cases, multiple back and forth switching between the stationary and the mobile states was achieved in nearly quantitative fashion. The ability to reversibly operate mechanical motion in an interlocked DNA nanostructure opens exciting new avenues in DNA nanotechnology. PMID- 22780816 TI - Synthesis and properties of dodecyl trehaloside detergents for membrane protein studies. AB - Sugar-based detergents, mostly derived from maltose or glucose, prevail in the extraction, solubilization, stabilization, and crystallization of membrane proteins. Inspired by the broad use of trehalose for protecting biological macromolecules and lipid bilayer structures, we synthesized new trehaloside detergents for potential applications in membrane protein research. We devised an efficient synthesis of four dodecyl trehalosides, each with the 12-carbon alkyl chain attached to different hydroxyl groups of trehalose, thus presenting a structurally diverse but related family of detergents. The detergent physical properties, including solubility, hydrophobicity, critical micelle concentration (CMC), and size of micelles, were evaluated and compared with the most popular maltoside analogue, beta-D-dodecyl maltoside (DDM), which varied from each other due to distinct molecular geometries and possible polar group interactions in resulting micelles. Crystals of 2-dodecyl trehaloside (2-DDTre) were also obtained in methanol, and the crystal packing revealed multiple H-bonded interactions among adjacent trehalose groups. The few trehaloside detergents were tested for the solubilization and stabilization of the nociceptin/orphanin FQ peptide receptor (ORL1) and MsbA, which belong to the G-protein coupled receptor (GPCR) and ATP-binding cassette transporter families, respectively. Our results demonstrated the utility of trehaloside detergents as membrane protein solubilization reagents with the optimal detergents being protein dependent. Continuing development and investigations of trehaloside detergents are attractive, given their interesting and unique chemical-physical properties and potential interactions with membrane lipids. PMID- 22780817 TI - Polymorphism of alkali bis(fluorosulfonyl)amides (M[N(SO2F)2], M = Na, K, and Cs). AB - The polymorphic behavior of Na, K, and Cs salts of the bis(fluorosulfonyl)amide anion N(SO(2)F)(2)(-) has been investigated by means of differential scanning calorimetry (DSC), single-crystal and powder X-ray diffraction, and Raman spectroscopy. All of the polymorphs observed in the present work (three for Na[N(SO(2)F)(2)], two for K[N(SO(2)F)(2)], and two for Cs[N(SO(2)F)(2)]) are stable enough for analyses at room temperature. With increasing temperature, form II of Na[N(SO(2)F)(2)] undergoes a solid-solid phase transition to form I, whereas another form (form III) crystallizes from the melt upon cooling. The anions in forms I and II of Na[N(SO(2)F)(2)] have trans and cis conformations, respectively, at 113 K, while cis-trans disorder is observed for the anion in form I at 298 K. Form I of K[N(SO(2)F)(2)], with a melting point of 375 K, is the stable form at room temperature, whereas solidification from the molten state during DSC gives rise to form II with a melting point of 336 K. Both forms I and II of K[N(SO(2)F)(2)] have anions in the cis conformation. The difference between the two potassium polymorphs arises from their crystal packing modes. In the case of Cs[N(SO(2)F)(2)], form I melts at 387 K, whereas form II undergoes a solid solid transition to form I at 330 K. The anion of form I in Cs[N(SO(2)F)(2)] has an oxygen/fluorine disorder that exhibits an oxygen/fluorine eclipsed conformation, even at 113 K. The powder X-ray diffraction pattern of form II matches that of the previously known Cs[N(SO(2)F)(2)] structure of the trans conformer. Vibrational frequencies observed with Raman spectroscopy do not necessarily show the same trend as those calculated for the energy-minimized cis or trans conformers in the gas phase due to packing effects. PMID- 22780818 TI - Efficacy and safety of pharmacotherapy for smoking cessation among pregnant smokers: a meta-analysis. AB - BACKGROUND: The efficacy and safety of pharmacotherapy for smoking cessation among pregnant smokers has not yet been established. OBJECTIVE: To investigate the efficacy and safety of pharmacotherapy for smoking cessation among pregnant smokers. SEARCH STRATEGY: A search was made of PubMed, Embase and CENTRAL in June 2011. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs and retrospective or prospective controlled studies were included. DATA COLLECTION AND ANALYSIS: The main analyses were designed to examine the efficacy of pharmacotherapy for smoking cessation among pregnant smokers based on the longest follow-up data available and from data obtained at the latest available time point in pregnancy in each study. MAIN RESULTS: Of 74 articles identified from the databases, seven studies (five RCTs, one quasi-RCT and one prospective study) involving a total of 1386 pregnant smokers, 732 in the intervention groups and 654 in the control groups, were included in the final analyses. In a fixed effects meta-analysis of all seven studies based on the longest follow-up data available, pharmacotherapy had a significant effect on smoking cessation (relative risk [RR] 1.80; 95% confidence interval [CI] 1.32-2.44). Subgroup meta analysis by type of study design also showed similar findings for RCTs (RR 1.48; 95% CI 1.04-2.09) and other types of studies (RR 3.25; 95% CI 1.65-6.39). The abstinence rate at late pregnancy in the intervention ranged from 7 to 22.6% (mean abstinence rate 13.0%; 95% CI 10.9-15.2%). A few minor adverse effects and serious adverse effects were reported in several studies. AUTHOR'S CONCLUSIONS: This study indicates that there may be clinical evidence to support the use of pharmacotherapy for smoking cessation among pregnant smokers. Further RCTs are needed. PMID- 22780819 TI - Episiotomy characteristics and risks for obstetric anal sphincter injuries: a case-control study. PMID- 22780821 TI - Avoiding episiotomy is the best strategy to prevent OASIS: response to the article 'episiotomy characteristics and risks for obstetric anal sphincter injuries: a case-control study'. PMID- 22780822 TI - Increasing trends in atonic postpartum haemorrhage in Ireland: an 11-year population-based cohort study. PMID- 22780825 TI - Primary surgical repair of anterior vaginal prolapse: a randomised trial comparing anatomical and functional outcome between anterior colporrhaphy and trocar-guided transobturator anterior mesh. PMID- 22780826 TI - Obstetric anal sphincter injury: a clinical audit. PMID- 22780831 TI - Reticular variant of mid-dermal elastolysis. AB - Mid-dermal elastolysis is a rare disorder characterised by focal loss of elastic tissue in the mid-dermis. Most patients present with lesions of fine wrinkling (type I) or perifollicular papules (type II). The reticular variant (type III) has been described less often in the literature. We report a case of a young woman with type III mid-dermal elastolysis. PMID- 22780832 TI - The five top bad reasons nurses don't publish in impactful journals. PMID- 22780834 TI - Oxidative and nitrosative-based signaling and associated post-translational modifications orchestrate the acclimation of citrus plants to salinity stress. AB - Reactive oxygen and nitrogen species are involved in a plethora of cellular responses in plants; however, our knowledge on the outcomes of oxidative and nitrosative signaling is still unclear. To better understand how oxidative and nitrosative signals are integrated to regulate cellular adjustments to external conditions, local and systemic responses were investigated in the roots and leaves of sour orange plants (Citrus aurantium L.) after root treatment with hydrogen peroxide (H(2) O(2) ) or sodium nitroprusside (a nitric oxide donor), followed by NaCl stress for 8 days. Phenotypic and physiological data showed that pre-exposure to these treatments induced an acclimation to subsequent salinity stress that was accompanied by both local and systemic H(2) O(2) and nitric oxide (NO) accumulation. Combined histochemical and fluorescent probe approaches showed the existence of a vascular-driven long-distance reactive oxygen species and NO signaling pathway. Transcriptional analysis of genes diagnostic for H(2) O(2) and NO signaling just after treatments or after 8 days of salt stress revealed tissue and time-specific mechanisms controlling internal H(2) O(2) and NO homeostasis. Furthermore, evidence is presented showing that protein carbonylation, nitration and S-nitrosylation are involved in acclimation to salinity stress. In addition, this work enabled characterization of potential carbonylated, nitrated and nitrosylated proteins with distinct or overlapping signatures. This work provides a framework to better understand the oxidative and nitrosative priming network in citrus plants subjected to salinity conditions. PMID- 22780835 TI - Effect of thermal desorption kinetics on vapor injection peak irregularities by a microscale gas chromatography preconcentrator. AB - Microscale gas chromatography (MUGC) is an emerging analytical technique for in situ analysis and on-site monitoring of volatile organic compounds (VOCs) in moderately complex mixtures. One of the critical subcomponents in a MUGC system is a microfabricated preconcentrator (MU-preconcentrator), which enables detection of compounds existing in indoor/ambient air at low (~sub ppb) concentrations by enhancing their signals. The prevailing notion is that elution peak broadening and tailing phenomena resulting from undesirable conditions of a microfabricated separation column (MU-column) are the primary sources of poor chromatographic resolution. However, previous experimental results indicate that the resolution degradation still remains observed for a MU-column integrated with other MUGC subcomponents even after setting optimal separation conditions. In this work, we obtain the evidence that the unoptimized MU-preconcentrator vapor release/injection performance significantly contributes to decrease the fidelity of MUGC analysis using our state-of-the-art passive preconcentrator microdevice. The vapor release/injection performance is highly affected by the kinetics of the thermal desorption of compounds trapped in the microdevice. Decreasing the heating rate by 20% from the optimal rate of 90 degrees Cs(-1) causes a 340% increase in peak tailing as well as 70% peak broadening (30% peak height reduction) to the microscale vapor injection process. PMID- 22780833 TI - Blast exposure induces post-traumatic stress disorder-related traits in a rat model of mild traumatic brain injury. AB - Blast related traumatic brain injury (TBI) has been a major cause of injury in the wars in Iraq and Afghanistan. A striking feature of the mild TBI (mTBI) cases has been the prominent association with post-traumatic stress disorder (PTSD). However, because of the overlapping symptoms, distinction between the two disorders has been difficult. We studied a rat model of mTBI in which adult male rats were exposed to repetitive blast injury while under anesthesia. Blast exposure induced a variety of PTSD-related behavioral traits that were present many months after the blast exposure, including increased anxiety, enhanced contextual fear conditioning, and an altered response in a predator scent assay. We also found elevation in the amygdala of the protein stathmin 1, which is known to influence the generation of fear responses. Because the blast overpressure injuries occurred while animals were under general anesthesia, our results suggest that a blast-related mTBI exposure can, in the absence of any psychological stressor, induce PTSD-related traits that are chronic and persistent. These studies have implications for understanding the relationship of PTSD to mTBI in the population of veterans returning from the wars in Iraq and Afghanistan. PMID- 22780836 TI - Outcome of frontal lobe epilepsy surgery. AB - PURPOSE: There is still controversy in deciding which patients with frontal lobe epilepsy (FLE) should undergo resective surgery, even though it is a well established therapy. The aim of this study is to define multiple outcome measures and determine whether there are certain subpopulations of preferred surgical candidates that have a more favorable seizure prognosis. METHODS: Fifty-eight patients underwent resective FLE surgery with a mean follow-up period of 79.3 months (range 12-208 months). Patient demographics, clinical seizure characteristics, seizure-onset zone within the frontal lobes, and diagnostic tests were tabulated. Engel class, International League Against Epilepsy (ILAE) class, postoperative seizure patterns, time to first recurrent seizure, and seizures and employment during the last year of follow-up were used as outcome measures. Neuropsychological performance and Beck Depression Inventory (BDI) scores were used to define neuropsychological outcome and examined as predictors of seizure outcome. KEY FINDINGS: Thirty-three (57%) patients with resective surgery had an Engel class I outcome and 29 (50%) had an ILAE class I outcome. Mean time to first seizure after surgery was 33.3 months (range 0-208). Only 14 patients (24%) were completely seizure-free without auras (Engel IA) throughout the entire follow-up period. The most common pattern of seizure recurrence was mixed, with prolonged periods of seizure freedom intermixed with recurrences. In addition, 32% of patients made gains in employment and 52% were able to reduce use of antiepileptic drugs (AEDs), although only 9% discontinued AEDs. No significant association was found between class I or class IA outcome and the presence of a focal magnetic resonance imaging (MRI) abnormality, any specific localization of seizure focus within the frontal lobe, or neuropsychological change. SIGNIFICANCE: Findings indicate that that long-term outcome is generally favorable in FLE resective surgery, and support the need for considering multiple outcome measures to more fully characterize clinically relevant postsurgical changes. Outcome can be favorable even in MRI-negative patients. PMID- 22780837 TI - Photoinduced damage to cellular DNA: direct and photosensitized reactions. AB - The survey focuses on recent aspects of photochemical reactions to cellular DNA that are implicated through the predominant formation of mostly bipyrimidine photoproducts in deleterious effects of human exposure to sunlight. Recent developments in analytical methods have allowed accurate and quantitative measurements of the main DNA photoproducts in cells and human skin. Highly mutagenic CC and CT bipyrimidine photoproducts, including cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) are generated in low yields with respect to TT and TC photoproducts. Another striking finding deals with the formation of Dewar valence isomers, the third class of bipyrimidine photoproducts that is accounted for by UVA-mediated isomerization of initially UVB generated 6-4PPs. Cyclobutadithymine (T<>T) has been unambiguously shown to be involved in the genotoxicity of UVA radiation. Thus, T<>T is formed in UVA-irradiated cellular DNA according to a direct excitation mechanism with a higher efficiency than oxidatively generated DNA damage that arises mostly through the Type II photosensitization mechanism. C<>C and C<>T are repaired at rates intermediate between those of T<>T and 6-4TT. Evidence has been also provided for the occurrence of photosensitized reactions mediated by exogenous agents that act either in an independent way or through photodynamic effects. PMID- 22780838 TI - Life-time risk for substance use among offspring of abusive family environment from the community. AB - The current study examined the cumulative risk, age of initiation, and functional impairments among adults with substance use problems (N = 1748) by child abuse status. Child abuse was associated with earlier initiation of marijuana, cocaine, and heroin use, and had greater risks for all the drugs studied (hazard ratios, 1.7-3.2). Furthermore, child abuse was associated with increased medical and functional impairments, including ER visits, health problems, drug dealing, drug dependence, and drug cravings. Provision of social services and parenting education during the perinatal period may prevent the long-term impact of child abuse on substance use and related impairments. The study's limitations are noted. PMID- 22780839 TI - Alcohol consumption and quality of life among young adults: a comparison among three European countries. AB - The study aims to investigate the relationship between alcohol consumption and quality of life (QoL) on a representative sample of adults aged 25-34 living in France, Italy, and the Netherlands (4,841 subjects). The data was collected in 2008 using telephone interviews and analyzed with cluster analysis using Ward's method. Results show that the impact of alcohol consumption on QoL depends mainly on predominant consumption style and drinking culture that should be investigated further to identify protective factors. PMID- 22780840 TI - The longitudinal prediction of alcohol consumption-related harms among young adults. AB - This study explores the longitudinal pathways by which risk and protective factors influence the development of alcohol-related harms in a representative community sample of 941 young adults (19-20 years) from Victoria, Australia, focusing on the role of concurrent risky drinking. Impulsivity at 15-16 years, alcohol-related harms at 15-16 years and 17-18 years, frequency of intoxication at 17-18 years, and antisocial behavior, friends' drinking and living arrangements at 19-20 years were directly related to alcohol-related harms, as well as indirectly related to harms through increased risky drinking. Paternal drinking at 17-18 years was directly related to alcohol-related harms. Friends' drinking at 19-20 years and alcohol-related harms at age 17-18 interacted with risky drinking to increase the likelihood of alcohol-related harms. Implications for intervention efforts are discussed. PMID- 22780842 TI - Engaging stakeholders in review and recommendations for models of outcome monitoring for substance abuse treatment. AB - We present an example of a collaborative process designed to review models of outcome monitoring for substance abuse services, with a view to assessing the feasibility of different approaches in Ontario, Canada. A conceptual framework that describes the parameters of an outcome monitoring system and four models of outcome monitoring were identified. Consultations were held with stakeholders (managers, directors, researchers, clinicians, and governmental representatives) about the types of information they would like to obtain from an outcome monitoring system. Our process is useful as a model for collaborative research with respect to performance measurement. The study's implications and limitations are noted. PMID- 22780841 TI - Knowledge, attitudes, and substance use practices among street children in Western Kenya. AB - The study describes the knowledge of and attitudes toward substance use among street-involved youth in Kenya, and how they relate to their substance use practices. In 2011, 146 children and youth ages 10-19 years, classified as either children on the street or children of the street were recruited to participate in a cross-sectional survey in Eldoret, Kenya. Bivariate analysis using chi2 or Fisher's Exact Test was used to test the associations between variables, and multiple logistic regression analysis was used to identify independent covariates associated with lifetime and current drug use. The study's limitations and source of funding are noted. PMID- 22780844 TI - Antiangiogenic therapeutic approaches in multiple myeloma. AB - Angiogenesis is a constant hallmark of multiple myeloma (MM) progression and has prognostic potential. The pathophysiology of MM-induced angiogenesis involves both direct production of angiogenic cytokines by plasma cells and their induction within the bone marrow microenvironment. An improved understanding of the importance of angiogenesis-related signaling in MM has allowed for the rational use of antiangiogenic therapies in this tumor. This review article summarizes the literature data concerning the employment of the most important antiangiogenic therapeutic agents actually used in preclinical models and clinical settings for the treatment of MM. PMID- 22780843 TI - Thermodynamic consequences of the hyperoxidized guanine lesion guanidinohydantoin in duplex DNA. AB - Guanidinohydantoin (Gh) is a hyperoxidized DNA lesion produced by oxidation of 8 oxo-7,8-dihydroguanine (8-oxoG). Previous work has shown that Gh is potently mutagenic in both in vitro and in vivo coding for G -> T and G -> C transversion mutations. In this work, analysis by circular dichroism shows that the Gh lesion does not significantly alter the global structure of a 15-mer duplex and that the DNA remains in the B-form. However, we find that Gh causes a large decrease in the thermal stability, decreasing the duplex melting temperature by ~17 degrees C relative to an unmodified duplex control. Using optical melting analysis and differential scanning calorimetry, the thermodynamic parameters describing duplex melting were also determined. We find that the Gh lesion causes a dramatic decrease in the enthalpic stability of the duplex. This enthalpic destabilization is somewhat tempered by entropic stabilization; yet, Gh results in an overall decrease in thermodynamic stability of the duplex relative to a control that lacks DNA damage, with a DeltaDeltaG degrees of -7 kcal/mol. These results contribute to our understanding of the consequences of hyperoxidation of G and provide insight into how the thermal and thermodynamic destabilization caused by Gh may influence replication and/or repair of the lesion. PMID- 22780845 TI - An interesting clinical case: variant of the cephalic vein emptying into the internal jugular vein. AB - This case report describes a 45-year-old patient who was referred to our center for surgical creation of long-term vascular access. Angiographic mapping revealed the left cephalic vein draining directly into the internal jugular vein rather than the axillary vein. The patient was scheduled for an ulnar artery to cephalic vein fistula. PMID- 22780846 TI - Regioselective and stepwise [8 + 2] cycloaddition reaction between alkynyl Fischer carbene complexes and tropothione. AB - The formal [8 + 2] cycloaddition reaction between alkynyl Fischer carbene complexes and tropothione leads to the regioselective formation of novel 3aH cyclohepta[b]thiophene carbene complexes. Computational DFT calculations indicate that the process proceeds stepwise via antiaromatic zwitterionic intermediates. PMID- 22780847 TI - Selective graphene formation on copper twin crystals. AB - Selective graphene growth on copper twin crystals by chemical vapor deposition has been achieved. Graphene ribbons can be formed only on narrow twin crystal regions with a (001) or high-index surface sandwiched between Cu crystals having (111) surfaces by tuning the growth conditions, especially by controlling the partial pressure of CH(4) in Ar/H(2) carrier gas. At a relatively low CH(4) pressure, graphene nucleation at steps on Cu (111) surfaces is suppressed, and graphene is preferentially nucleated and formed on twin crystal regions. Graphene ribbons as narrow as ~100 nm have been obtained in experiments. The preferential graphene nucleation and formation seem to be caused primarily by a difference in surface-dependent adsorption energies of reactants, which has been estimated by first principles calculations. Concentrations of reactants on a Cu surface have also been analyzed by solving a diffusion equation that qualitatively explains our experimental observations of the preferential graphene nucleation. Our findings may lead to self-organizing formation of graphene nanoribbons without reliance on top-down approaches in the future. PMID- 22780848 TI - Plasma free choline is a novel non-invasive biomarker for early-stage non alcoholic steatohepatitis: A multi-center validation study. AB - AIM: Choline is a dietary component that is crucial for normal cellular function. Choline is predominantly absorbed from the small intestine and completely metabolized in the liver. We recently demonstrated that free choline (fCh) levels in blood reflect the level of phosphatidylcholine synthesis in the liver and is correlated with the onset of non-alcoholic steatohepatitis (NASH). Our aim here was to validate the utility of this biomarker for NASH diagnosis. METHODS: Our cohort consisted of 110 patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) from four centers across Japan and 25 age-matched healthy controls. Plasma fCh levels were measured using high-performance liquid chromatography. RESULTS: Patients with diagnosed or borderline NASH had significantly increased plasma fCh levels when compared with control subjects, or patients not diagnosed with NASH. Interestingly, an association between plasma fCh levels and expression of microsomal triglyceride transfer protein, which catalyzes the transfer of triglyceride, was reflected in the markedly negative correlation between these two variables in patients with NAFLD. Moreover, the grade of liver steatosis and fibrosis stage increased with increasing plasma fCh levels (P < 0.05). The area under the receiver-operating characteristic (ROC) curves for NASH, including borderline diagnosis, was 0.811. Additionally, the areas under the ROC for fibrosis stage were 0.816 for >stage 1, 0.805 for >stage 2, 0.809 for >stage 3 and 0.818 for >stage 4. CONCLUSION: Plasma fCh levels are closely related to the grade of liver steatosis and fibrosis, and predict NASH severity. Plasma fCh levels are therefore a potential diagnostic marker for early stage NASH in clinical practice. PMID- 22780849 TI - Association of Ephrin receptor A3 gene polymorphism with susceptibility to chronic severe hepatitis B. AB - AIM: Previous research has suggested that Ephrin receptor A3 (EphA3) plays signaling roles in the processes of inflammation by regulating lymphocyte migration and proliferation. In this study, we investigated whether the EphA3 gene polymorphism was associated with disease progression of chronic hepatitis B virus (HBV) infection. METHODS: The EphA3 variant rs9310117 was genotyped in 1245 unrelated Han Chinese HBV carriers including 800 cases and 445 controls. chi(2) test was used to examine the difference in allele frequencies and genotype distributions between groups. The association between the polymorphism and disease progression of HBV infection was conducted by unconditional logistic regression analysis. RESULTS: Statistical analysis revealed that the genetic variant was significantly associated with the occurrence of chronic severe hepatitis B (CSHB). We observed that subjects bearing at least one T allele (C/T or T/T genotype) had a decreased susceptibility to chronic severe hepatitis B compared with those bearing C/C genotype (P = 0.003, odds ratio = 0.560; 95% confidence interval, 0.381-0.824, recessive model). Genotype C/T had also been confirmed to protect subjects from suffering chronic severe hepatitis B (P = 0.001, odds ratio = 0.498; 95% confidence interval, 0.330-0.752, additive model). CONCLUSION: Our results suggest that the genetic alteration at EphA3 locus plays a role in the occurrence of chronic severe hepatitis B. PMID- 22780850 TI - Adhesion mechanisms of the contact interface of TiO2 nanoparticles in films and aggregates. AB - Fundamental knowledge about the mechanisms of adhesion between oxide particles with diameters of few nanometers is impeded by the difficulties associated with direct measurements of contact forces at such a small size scale. Here we develop a strategy based on AFM force spectroscopy combined with all-atom molecular dynamics simulations to quantify and explain the nature of the contact forces between 10 nm small TiO(2) nanoparticles. The method is based on the statistical analysis of the force peaks measured in repeated approaching/retracting loops of an AFM cantilever into a film of nanoparticle agglomerates and relies on the in situ imaging of the film stretching behavior in an AFM/TEM setup. Sliding and rolling events first lead to local rearrangements in the film structure when subjected to tensile load, prior to its final rupture caused by the reversible detaching of individual nanoparticles. The associated contact force of about 2.5 nN is in quantitative agreement with the results of molecular dynamics simulations of the particle-particle detachment. We reveal that the contact forces are dominated by the structure of water layers adsorbed on the particles' surfaces at ambient conditions. This leads to nonmonotonous force-displacement curves that can be explained only in part by classical capillary effects and highlights the importance of considering explicitly the molecular nature of the adsorbates. PMID- 22780851 TI - A combined experimental and modeling approach to study the effects of high-shear wet granulation process parameters on granule characteristics. AB - The purpose of the current work is to study the effects of high-shear wet granulation process parameters on granule characteristics using both experimental and modeling techniques. A full factorial design of experiments was conducted on three process parameters: water amount, impeller speed and wet massing time. Statistical analysis showed that the water amount has the largest impact on the granule characteristics, and that the effect of other process variables was more pronounced at higher water amount. At high water amounts, an increase in impeller speed and/or wet massing time showed a decrease in granule porosity and compactability. A strong correlation between granule porosity and compactability was observed. A three-dimensional population balance model which considers agglomeration and consolidation was employed to model the granulation process. The model was calibrated using the particle size distribution from an experimental batch to ensure a good match between the simulated and experimental particle size distribution. The particle size distribution of three other batches were predicted, each of which was manufactured under different process parameters (water amount, impeller speed and wet massing time). The model was able to capture and predict successfully the shifts in granule particle size distribution with changes in these process parameters. PMID- 22780852 TI - Human cadaver study evaluating a new measurement technique for graft volumes after sinus floor elevation. AB - PURPOSE: Volumetric data can be used as complementary information to characterize grafting materials. The aim of this cadaveric study was to analyze a noncommercial measurement technique based on the novel concept of an "interactive rigid registration algorithm" (IRRA). Parameters analyzed included the reproducibility of IRRA measurements and their reliability in comparison with the established measurement technique of "region growing segmentation thresholding" (RGST). MATERIALS AND METHODS: Three human skulls were used to simulate a total of 18 sinus grafts, using three incremental grafting procedures in each sinus (three skulls *t wo sinuses * three grafting increments). Radiopaque impression material was used for the simulated grafts, whose volumes were recorded by computed tomography from three different tilt angles. The reproducibility of IRRA measurements and the reliability of volumetric results obtained with both the IRRA and RGST techniques were evaluated by appropriate intraclass correlation coefficient (ICC) and Bland-Altman analysis. RESULTS: ICC greater than 0.9 indicated close to perfect agreement of the results obtained with both methods and good reproducibility of the IRRA measurements. Bland-Altman analysis demonstrated good inter-method and intramethod agreement. CONCLUSIONS: The IRRA measurement technique can be recommended as a noninvasive tool to evaluate graft volumes in human maxillary sinuses. PMID- 22780853 TI - Managing treatment for end-stage renal disease--a qualitative study exploring cultural perspectives on facilitators and barriers to treatment adherence. AB - Although adherence to hemodialysis (HD) regimes is important to maximise good clinical outcomes, it remains suboptimal and not well understood, particularly for those in non-Western settings and patients from Asian cultures. This qualitative study sought to explore cultural perspectives on facilitators and barriers to treatment adherence in HD patients. A descriptive exploratory design was used for the study, incorporating individual semi-structured interviews (n = 17) and three focus groups (n = 20). Each interview/focus group was audio-taped and transcribed verbatim, and coding was conducted by two coders using an iterative process. Study participants identified personal and social/contextual factors as major barriers or facilitators of treatment adherence. Barriers include time consumption, forgetfulness, concerns about safety, poor knowledge/understanding, poor communication and lack of control/social pressure. Participants also identified facilitators, both internal (self-initiated) and external (initiated by family, health care professional and peers) to ensure treatment adherence. These included support from family members and social obligation towards others, risk perception, establishment of routines and peer support. Internal and external factors can hinder or facilitate adherence to diet, fluid and medications in the context of dialysis. Several of these barriers/facilitators can be effectively addressed in the context of interventions and psycho-educational programmes. PMID- 22780856 TI - Cardiovascular diseases and the health-related quality of life after total hip replacement. AB - AIMS AND OBJECTIVES: To evaluate to what degree total hip replacement, or co morbidities or their progression, influence the health-related quality of life of patients after the operation. We have looked for an objective method to reflect the severity of cardiovascular diseases and to better characterise the health related quality of life of patients with total hip replacement. BACKGROUND: The main weakness of the different health-related quality of life methods that are applied to the analysis is the lack of information regarding the contributory role of co-morbidities, especially cardiovascular diseases. DESIGN: Retrospective longitudinal study. METHODS: This study involved 109 patients who had had total hip replacement. The patients' health status - objective and subjective functional performance at the time of operation and five years later - was evaluated using questionnaires (including EQ-5D and Western Ontario and McMaster Universities' Ostoearthritis Index scores) and the hospital database. An Objective Cardiovascular Classification grouping was developed to evaluate the deterioration of cardiovascular diseases. RESULTS: The subjective assessment of the patients' health status at Year 5 revealed highly significant differences between healthy and sick patients in respect of EQ-5D and Objective Cardiovascular Classification but not in the case of the Western Ontario and McMaster Universities' Ostoearthritis Index scores. Evaluating postoperative subjective health awareness, a higher sensitivity and specificity and a significantly better individual-discriminating role was demonstrated in Objective Cardiovascular Classification vs. EQ-5D. CONCLUSION: After successful total hip replacement postoperative health awareness is influenced mainly by existing and developing cardiovascular diseases. It seems to be the case that for patients with significant hypertension, ischaemic heart disease or chronic heart failure, even successful surgery will not improve the patients' overall feeling of health. RELEVANCE TO CLINICAL PRACTICE: Nursing care of patients with total hip replacement, in respect of cardiovascular diseases, can contribute a better health-related quality of life. PMID- 22780855 TI - The use of magnetic resonance spectroscopy in the subacute evaluation of athletes recovering from single and multiple mild traumatic brain injury. AB - Advanced neuroimaging techniques have shown promise in highlighting the subtle changes and nuances in mild traumatic brain injury (MTBI) even though clinical assessment has shown a return to pre-injury levels. Here we use 1H-magnetic resonance spectroscopy (1H-MRS) to evaluate the brain metabolites N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) in the corpus callosum in MTBI. Specifically, we looked at the NAA/Cho, NAA/Cr, and Cho/Cr ratios in the genu and splenium. We recruited 20 normal volunteers (NV) and 28 student athletes recovering from the subacute phase of MTBI. The MTBI group was categorized based upon the number of MTBIs and time from injury to 1H-MRS evaluation. Significant reductions in NAA/Cho and NAA/Cr ratios were seen in the genu of the corpus callosum, but not in the splenium, for MTBI subjects, regardless of the number of MTBIs. MTBI subjects recovering from their first MTBI showed the greatest alteration in NAA/Cho and NAA/Cr ratios. Time since injury to 1H-MRS acquisition was based upon symptom resolution and did not turn out to be a significant factor. We observed that as the number of MTBIs increased, so did the length of time for symptom resolution. Unexpected findings from this study are that MTBI subjects showed a trend of increasing NAA/Cho and NAA/Cr ratios that coincided with increasing number of MTBIs. PMID- 22780857 TI - Addressing adult hearing loss in primary care. AB - AIMS: To (a) determine the extent to which primary care providers screen adults for environmental or occupational hearing loss during the primary care visit and (b) determine what techniques are used to screen for hearing loss in the adult primary care patient. BACKGROUND: Although the prevalence of hearing loss is high, the frequency and techniques of screening for hearing loss among primary care providers are unknown. According to the United States Preventative Task Force, hearing screening promotes early detection, adequate treatment, and improved quality of life. DESIGN: It is a retrospective audit. METHODS: Thirty client records were randomly selected from two clinics in 2009 for this retrospective patient record audit. RESULTS/FINDINGS: Physical assessment of the structure of the auditory system was completed in all cases selected. Hearing acuity in all cases was determined by patient self-assessment, as indicated on patient-completed history forms; there was no documentation of objective assessment of auditory function. CONCLUSION: Given the low correlation between perceived and measured hearing ability, assessment of hearing ability by patient report alone may result in failure to detect hearing loss. Research into the nature and extent of barriers to hearing assessment in primary care needs to be explored, and criteria for screening of adults in the primary care setting should be established. PMID- 22780858 TI - Dravet syndrome: seizure control and gait in adults with different SCN1A mutations. AB - PURPOSE: Dravet syndrome (DS) is an aggressive epileptic encephalopathy. Pharmacoresistant seizures of several types plague most patients with DS throughout their lives. Gait difficulties are a common, but inconsistent finding. The majority of cases are caused by mutations in the SCN1A gene, but little information is available about how particular mutations influence the adult phenotype. The purpose of this study is to correlate different types of SCN1A mutations and (1) seizure control, (2) occurrence of convulsive status epilepticus (cSE), and (3) the presence of crouch gait in adult patients. METHODS: In a cohort of 10 adult patients with DS caused by SCN1A mutations, we investigated seizure frequency, history of cSE, and gait. All patients were identified in the epilepsy clinic between 2009 and 2011. SCN1A mutations were divided into four different groups based on location or effect of the mutation. Retrospective chart review and recent physical examination were completed in all cases. KEY FINDINGS: All patients had a pathogenic mutation in the SCN1A gene. Four SCN1A mutations have not been described previously. Greater than 90% seizure reduction was observed (compared to childhood frequency) in six of seven patients with missense mutations in the pore-forming region (PFR) of the Na(v) 1.1 protein (group A) and nonsense mutations (group B). One patient with a splice-site mutation (group C) and another with a mutation outside the PFR (group D) became free of all types of seizures. cSE after the age of 19 years was observed in only one patient. Crouch gait, without spasticity, is identified as an element of the adult DS phenotype. However, only one half of our adult DS cohort demonstrated crouch gait. This feature was observed in five of seven patients from groups A and B. SIGNIFICANCE: This study shows that seizure control improves and cSE become less frequent in DS as patients age, independent of their SCN1A mutation type. Complete seizure freedom was seen in two patients (groups C and D). Finally, this study shows that in DS, crouch gait can be observed in up to 50% of adults with SCN1A mutation. Although no definite statistical correlations could be made due to the small number of patients, it is interesting to note that crouch gait was observed only in those patients with nonsense mutations or mutations in the PFR. Future studies with larger cohorts will be required to formally assess an association of gait abnormalities with particular SCN1A mutations. PMID- 22780859 TI - Children's reasoning about self-presentation following rule violations: the role of self-focused attention. AB - Rule violations are likely to serve as key contexts for learning to reason about public identity. In an initial study with 91 children aged 4-9years, social emotions and self-presentational concerns were more likely to be cited when children were responding to hypothetical vignettes involving social-conventional rather than moral violations. In 2 further studies with 376 children aged 4 9years, experimental manipulations of self-focused attention (either by leading children to believe they were being video-recorded or by varying audience reactions to transgressions) were found to elicit greater attention to social evaluation following moral violations, although self-presentational concerns were consistently salient in the context of social-conventional violations. The role of rule transgressions in children's emerging self-awareness and social understanding is discussed. PMID- 22780860 TI - Personal sun exposure and serum 25-hydroxy vitamin D concentrations. AB - Solar ultraviolet-B radiation (UVB) is essential for epidermal vitamin D production. We aimed to quantitate the relationship between personal solar UV exposure and serum 25hydroxy vitamin D (25[OH]D) concentration. Blood was collected for 25(OH)D analysis in 207 South Australian adults aged 27-61 years. At the time of blood collection, each participant completed a questionnaire, which included a calendar for recall of sun exposure in the preceding 16 weeks. We examined the association between solar UV exposure and serum 25(OH)D graphically from smoothed scatter plots, and modeled it using multiple linear regression, with age, sex and body mass index as covariates. Estimated erythemal solar UV exposure in the 6 weeks before blood collection best predicted serum 25(OH)D concentrations. Serum 25(OH)D rose with increasing personal solar UV exposure to a maximum of about 89 nmol L(-1) at an estimated mean weekly solar erythemal UV exposure of about 1230 mJ cm(-2). The maximum was the same after accounting for clothing coverage and was reached at an estimated whole body equivalent exposure to ambient UV of ca 700 mJ cm(-2). These results suggest that an average maximum serum 25(OH)D of ca 89 nmol L(-1) is achieved from sun exposure in a healthy Australian adult population. PMID- 22780861 TI - Point group symmetry determination via observables revealed by polarized second harmonic generation microscopy: (1) theory. AB - We present a methodology based on polarization-controlled second-harmonic generation microscopy that allows one to determine the point group symmetry of noncentrosymmetric structures in situ and in vivo in complex systems regardless of the occurrence of periodicity. Small, randomly oriented structures suffice for the analysis, which is based on simple recognition of observables in four tests. These can be performed in any standard SHG-microscope that allows polarization control of the incident and detected light. The method is resilient to birefringence and light dispersion. PMID- 22780862 TI - Cationic antimicrobial peptides disrupt the Streptococcus pyogenes ExPortal. AB - Although they possess a well-characterized ability to porate the bacterial membrane, emerging research suggests that cationic antimicrobial peptides (CAPs) can influence pathogen behaviour at levels that are sublethal. In this study, we investigated the interaction of polymyxin B and human neutrophil peptide (HNP-1) with the human pathogen Streptococcus pyogenes. At sublethal concentrations, these CAPs preferentially targeted the ExPortal, a unique microdomain of the S. pyogenes membrane, specialized for protein secretion and processing. A consequence of this interaction was the disruption of ExPortal organization and a redistribution of ExPortal components into the peripheral membrane. Redistribution was associated with inhibition of secretion of certain toxins, including the SpeB cysteine protease and the streptolysin O (SLO) cytolysin, but not SIC, a protein that protects S. pyogenes from CAPs. These data suggest a novel function for CAPs in targeting the ExPortal and interfering with secretion of factors required for infection and survival. This mechanism may prove valuable for the design of new types of antimicrobial agents to combat the emergence of antibiotic-resistant pathogens. PMID- 22780863 TI - Gibbs free energy of formation of chlordecone and potential degradation products: implications for remediation strategies and environmental fate. AB - Chlordecone (C(10)Cl(10)O; CAS number 143-50-0) has been used extensively as an organochlorine insecticide but is nowadays banned under The Stockholm Convention on Persistent Organic Pollutants (POPs). A search for chlordecone-respiring organisms and choosing between reductive versus oxidative remediation tools and strategies to clean up chlordecone-polluted environments would benefit from the availability of Gibbs free energy data of chlordecone and its potential dechlorination products. Presently such data are not available. Polycyclic "cage" molecules of which chlordecone is an example contain considerable strain energy. It is not a priori clear how this affects the thermodynamic properties of the chlorinated members of this unique class of compounds and to what extent redox potentials for the halogenated congeners are different from those of other aliphatic and aromatic organohalogens. We performed ab initio quantum chemical calculations to estimate Delta(f)H(m) degrees and Delta(f)G(m) degrees values of chlordecone and selected dechlorination products and used these data to calculate their Gibbs free energy and redox potential. With redox potentials in the range of 336-413 mV chlordecone has an E(o)' value similar to that of other organochlorines. The results indicate that there are no thermodynamic reasons why chlordecone-respiring or -fermenting organisms should not exist. PMID- 22780864 TI - Effect on ligament marker expression by direct-contact co-culture of mesenchymal stem cells and anterior cruciate ligament cells. AB - Ligament and tendon repair is an important topic in orthopedic tissue engineering; however, the cell source for tissue regeneration has been a controversial issue. Until now, scientists have been split between the use of primary ligament fibroblasts or marrow-derived mesenchymal stem cells (MSCs). The objective of this study was to show that a co-culture of anterior cruciate ligament (ACL) cells and MSCs has a beneficial effect on ligament regeneration that is not observed when utilizing either cell source independently. Autologous ACL cells (ACLcs) and MSCs were isolated from Yorkshire pigs, expanded in vitro, and cultured in multiwell plates in varying %ACLcs/%MSCs ratios (100/0, 75/25, 50/50, 25/75, and 0/100) for 2 and 4 weeks. Quantitative mRNA expression analysis and immunofluorescent staining for ligament markers Collagen type I (Collagen-I), Collagen type III (Collagen-III), and Tenascin-C were performed. We show that Collagen-I and Tenascin-C expression is significantly enhanced over time in 50/50 co-cultures of ACLcs and MSCs (p<=0.03), but not in other groups. In addition, Collagen-III expression was significantly greater in MSC-only cultures (p<=0.03), but the Collagen-I-to-Collagen-III ratio in 50% co-culture was closest to native ligament levels. Finally, Tenascin-C expression at 4 weeks was significantly higher (p<=0.02) in ACLcs and 50% co-culture groups compared to all others. Immunofluorescent staining results support our mRNA expression data. Overall, 50/50 co-cultures had the highest Collagen-I and Tenascin-C expression, and the highest Collagen-I-to-Collagen-III ratio. Thus, we conclude that using a 50% co culture of ACLcs and MSCs, instead of either cell population alone, may better maintain or even enhance ligament marker expression and improve healing. PMID- 22780865 TI - A dysfunctional peritoneal dialysis catheter: imaging the problem. PMID- 22780866 TI - Synthesis of 5-iodo-1,4-disubstituted-1,2,3-triazoles mediated by in situ generated copper(I) catalyst and electrophilic triiodide ion. AB - Mixing copper(II) perchlorate and sodium iodide solutions results in copper(I) species and the electrophilic triiodide ions, which collectively mediate the cycloaddition reaction of organic azide and terminal alkyne to afford 5-iodo-1,4 disubstituted-1,2,3-triazoles. One molar equivalent of an amine additive is required for achieving a full conversion. Excessive addition of the amine compromises the selectivity for 5-iodo-1,2,3-triazole by promoting the formation of 5-proto-1,2,3-triazole. Based on preliminary kinetic and structural evidence, a mechanistic model is formulated in which a 5-iodo-1,2,3-triazole is formed via iodination of a copper(I) triazolide intermediate by the electrophilic triiodide ions (and possibly triethyliodoammonium ions). The experimental evidence explains the higher reactivity of the in situ generated copper(I) species and triiodide ion in the formation of 5-iodo-1,2,3-triazoles than that of the pure forms of copper(I) iodide and iodine. PMID- 22780867 TI - Application of decoy oligonucleotides as novel therapeutic strategy: a contemporary overview. AB - Molecular therapy is emerging as a potential strategy for the treatment of many diseases. Correct regulation of gene expression is essential for both, to normal development and proper functioning of the all the organisms. Even after four decades of intensive research, it is still a major problem from regulatory and technical point of view, to replace defective genes. The technology of decoy oligonucleotides has received considerable attention to treat and cure a variety of diseases and abnormal physiological conditions, because they provide a rational way to design and selective regulation of a specific gene expression. Decoy oligonucleotides are widely used as inhibitors of specific gene expression because they can offer exciting possibility of expression and blocking of a particular gene without any changes in the functions of other genes. Advances in the decoy oligonucleotides are rapidly paving the way to new insights into the origin and treatment of inflammatory, cancer and/or other immune disorders. The review covers the progress achieved towards the development of decoy oligonucleotides as a potential strategy in a new class of molecular therapy. PMID- 22780868 TI - Enhancement of poly(vinyl ester) solubility in supercritical CO2 by partial fluorination: the key role of polymer-polymer interactions. AB - An enhancement of poly(vinyl ester) solubility in supercritical carbon dioxide (sc-CO(2)) can be achieved by decreasing the strength of the polymer-polymer interactions. To demonstrate this, a library of statistical copolymers of vinyl acetate and vinyl trifluoroacetate was synthesized by RAFT/MADIX polymerization with varying compositions at a given number-average molecular weight. These copolymers exhibited unprecedentedly low cloud-point pressures in sc-CO(2) at 40 degrees C compared with previously reported poly(vinyl esters). Surface tension measurements combined with a computational approach evidenced the prominent role played by polymer-polymer interactions. PMID- 22780869 TI - The host endocytic pathway is essential for Plasmodium berghei late liver stage development. AB - The obligate intracellular liver stage of the Plasmodium parasite represents a bottleneck in the parasite life cycle and remains a promising target for therapeutic intervention. During this stage, parasites undergo dramatic morphological changes and achieve one of the fastest replication rates among eukaryotic species. Nevertheless, relatively little is known about the parasite interactions with the host hepatocyte. Using immunofluorescence, live cell imaging and electron microscopy, we show that Plasmodium berghei parasites are surrounded by vesicles from the host late endocytic pathway. We found that these vesicles are acidic and contain the membrane markers Rab7a, CD63 and LAMP1. When host cell vesicle acidification was disrupted using ammonium chloride or Concanamycin A during the late liver stage of infection, parasite survival was not affected, but schizont size was significantly decreased. Furthermore, when the host cell endocytic pathway was loaded with BSA-gold, gold particles were found within the parasite cytoplasm, showing the transport of material from the host endocytic pathway toward the parasite interior. These observations reveal a novel Plasmodium-host interaction and suggest that vesicles from the host endolysosomal pathway could represent an important source of nutrients exploited by the fast-growing late liver stage parasites. PMID- 22780871 TI - Resampling versus repair in evolution strategies applied to a constrained linear problem. AB - We study the behaviour of multi-recombination evolution strategies for the problem of maximising a linear function with a single linear constraint. Two variants of the algorithm are considered: a strategy that resamples infeasible candidate solutions and one that applies a simple repair mechanism. Integral expressions that describe the strategies' one-generation behaviour are derived and used in a simple zeroth order model for the steady state attained when operating with constant step size. Applied to the analysis of cumulative step size adaptation, the approach provides an intuitive explanation for the qualitative difference in the algorithm variants' behaviour. The findings have implications for the design of constraint handling techniques to be used in connection with cumulative step size adaptation. PMID- 22780870 TI - Cu-64-labeled lactam bridge-cyclized alpha-MSH peptides for PET imaging of melanoma. AB - The purpose of this study was to examine and compare the melanoma targeting and imaging properties of (64)Cu-NOTA-GGNle-CycMSH(hex) {(64)Cu-1,4,7 triazacyclononane-1,4,7-triacetic acid-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys] CONH2} and (64)Cu-DOTA-GGNle-CycMSH(hex) {(64)Cu-1,4,7,10-tetraazacyclononane 1,4,7,10-tetraacetic acid-GGNle-CycMSH(hex)}. Two lactam bridge-cyclized peptides, NOTA-GGNle-CycMSH(hex) and DOTA-GGNle-CycMSH(hex), were synthesized using fluorenylmethyloxy carbonyl (Fmoc) chemistry. The melanocortin-1 (MC1) receptor binding affinity of NOTA-GGNle-CycMSH(hex) was determined in B16/F1 melanoma cells and compared with DOTA-GGNle-CycMSH(hex). The melanoma targeting and imaging properties of (64)Cu-NOTA-GGNle-CycMSH(hex) and (64)Cu-DOTA-GGNle CycMSH(hex) were determined in B16/F1 melanoma-bearing C57 mice. NOTA-GGNle CycMSH(hex) and DOTA-GGNle-CycMSH(hex) displayed comparable MC1 receptor binding affinities (1.6 vs 2.1 nM). The substitution of DOTA with NOTA dramatically increased the melanoma uptake and decreased the renal and liver uptake of (64)Cu NOTA-GGNle-CycMSH(hex). The tumor uptake of (64)Cu-NOTA-GGNle-CycMSH(hex) was between 12.39 +/- 1.61 and 12.71 +/- 2.68% ID/g at 0.5, 2, and 4 h postinjection. The accumulation of (64)Cu-NOTA-GGNle-CycMSH(hex) activity in normal organs was lower than 1.02% ID/g except for the kidneys 2, 4, and 24 h postinjection. The tumor/liver uptake ratios of (64)Cu-NOTA-GGNle-CycMSHhex were 17.96, 16.95, and 8.02, whereas the tumor/kidney uptake ratios of (64)Cu-NOTA-GGNle-CycMSH(hex) were 2.52, 3.60, and 5.74 at 2, 4, and 24 h postinjection, respectively. Greater than 91% of the injected radioactivity cleared through the urinary system by 2 h postinjection. The substitution of DOTA with NOTA resulted in a dramatic increase in melanoma uptake and decrease in renal and liver uptake of (64)Cu-NOTA-GGNle CycMSH(hex) as compared to (64)Cu-DOTA-GGNle-CycMSH(hex). High melanoma uptake coupled with low accumulation in nontarget organs suggested (64)Cu-NOTA-GGNle CycMSH(hex) as a lead radiolabeled peptide for melanoma imaging and therapy. PMID- 22780872 TI - Effect of dental implant diameter on fatigue performance. Part II: failure analysis. AB - PURPOSE: The purpose of this study was to perform fracture mode analysis for in vitro failed implants in order to evaluate the relation between the fracture mode obtained and the implants' fatigue behavior. MATERIALS AND METHODS: Eighty fractured dental implants were analyzed after being tested for fatigue performance. A macroscopic failure analysis was performed, which evaluated and located the fracture modes obtained, followed by a microscopic failure analysis comprising a detailed scanning electron microscopy (SEM) fractographic analysis. RESULTS: Four distinctive fracture loci were identified and macrofracture mode analysis was performed, showing that all 5-mm implants that fractured were fractured at the abutment neck and screw. In the 3.75-mm group, 44.4% were fractured at the implant neck and 55.5% at the implants second thread. Fifty-two percent of the 3.3-mm fractured implants had it at the implants second tread and 48% at the implants third thread. The implant's metallographic sections revealed that the different fracture loci were located where thin metal cross sections and sharp notches coexist. Using SEM, we were able to characterize the failure micromechanisms and fatigue characterization as transgranular fracture and arrays of secondary parallel microcracks at relatively low magnifications and classic fatigue striations at much higher magnifications. CONCLUSIONS: The results of this study indicate that proper implant design is crucial to ensure long-term fatigue performance for dental implants. The combination of sharp notches (thread) and narrow metal cross section is quite deleterious for fatigue resistance. PMID- 22780873 TI - Sildenafil-induced pigmented purpuric dermatosis. AB - We present a patient who experienced pigmented purpura 10 days after initiating sildenafil. The eruption cleared several weeks after discontinuation of the medication. To the best of our knowledge, this is the first case of pigmented purpuric dermatosis reported due to sildenafil. PMID- 22780874 TI - Target-triggered polymerization for biosensing. AB - Because of the potential applications of biosensors in clinical diagnosis, biomedical research, environmental analysis, and food quality control, researchers are very interested in developing sensitive, selective, rapid, reliable, and low-cost versions of these devices. A classic biosensor directly transduces ligand-target binding events into a measurable physical readout. Because of the limited detection sensitivity and selectivity in earlier biosensors, researchers have developed a number of sensing/signal amplification strategies. Through the use of nanostructured or long chain polymeric materials to increase the upload of signal tags for amplification of the signal readout associated with the ligand-target binding events, researchers have achieved high sensitivity and exceptional selectivity. Very recently, target-triggered polymerization-assisted signal amplification strategies have been exploited as a new biosensing mechanism with many attractive features. This strategy couples a small initiator molecule to the DNA/protein detection probe prior to DNA hybridization or DNA/protein and protein/protein binding events. After ligand target binding, the in-situ polymerization reaction is triggered. As a result, tens to hundreds of small monomer signal reporter molecules assemble into long chain polymers at the location where the initiator molecule was attached. The resulting polymer materials changed the optical and electrochemical properties at this location, which make the signal easily distinguishable from the background. The assay time ranged from minutes to hours and was determined by the degree of amplification needed. In this Account, we summarize a series of electrochemical and optical biosensors that employ target-triggered polymerization. We focus on the use of atom transfer radical polymerization (ATRP), as well as activator generated electron transfer for atom transfer radical polymerization (AGET ATRP) for in-situ formation of polymer materials for optically or electrochemically transducing DNA hybridization and protein-target binding. ATRP and AGET ATRP can tolerate a wide range of functional monomers. They also allow for the preparation of well-controlled polymers with narrow molecular weight distribution, which was predetermined by the concentration ratio of the consumed monomer to the introduced initiator. Because the reaction initiator can be attached to a variety of detection probes through well-established cross-linking reactions, this technique could be expanded as a universal strategy for the sensitive detection of DNA and proteins. We see enormous potential for this new sensing technology in the development of portable DNA/protein sensors for point-of-need applications. PMID- 22780876 TI - Multiple batch manufacturing of theophylline pellets using the wet extrusion/spheronization process with kappa-carrageenan as pelletisation aid. AB - kappa-Carrageenan has been suggested as a pelletisation aid for wet extrusion/spheronization processes for several years. Until now there have been no systematic investigations regarding process development and stability for long term production. The aim of this study was to develop a high drug-loaded pellet formulation with kappa-carrageenan, so that a robust process cycle occurred over the course of several hours. Binary mixtures of kappa-carrageenan and theophylline monohydrate were used and the drug content was varied from 90 to 95%. A twin-screw extruder was used; the power consumption and feed rates were recorded. The pellets were characterized by aspect ratio, diameter, 10% interval, tensile strength and dissolution behavior. The process ran on two occasions for 4.5 h each time. During the extrusion process neither the power consumption nor the feed rates differed significantly, so there was no need to stop the process or change the extrusion parameters. Regarding the spheronization, a cleaning of the spheroniser friction plate was necessary every five batches due to packing of the material on this plate. Overall the resulting pellets showed reproducible and adequate qualities regarding all investigated properties. In conclusion a robust pelletisation process over several hours could be verified. It was possible to produce 42 kg of pellets with adequate properties, without any problems during the process. PMID- 22780875 TI - Clustered metallothionein genes are co-regulated in rice and ectopic expression of OsMT1e-P confers multiple abiotic stress tolerance in tobacco via ROS scavenging. AB - BACKGROUND: Metallothioneins (MT) are low molecular weight, cysteine rich metal binding proteins, found across genera and species, but their function(s) in abiotic stress tolerance are not well documented. RESULTS: We have characterized a rice MT gene, OsMT1e-P, isolated from a subtractive library generated from a stressed salinity tolerant rice genotype, Pokkali. Bioinformatics analysis of the rice genome sequence revealed that this gene belongs to a multigenic family, which consists of 13 genes with 15 protein products. OsMT1e-P is located on chromosome XI, away from the majority of other type I genes that are clustered on chromosome XII. Various members of this MT gene cluster showed a tight co regulation pattern under several abiotic stresses. Sequence analysis revealed the presence of conserved cysteine residues in OsMT1e-P protein. Salinity stress was found to regulate the transcript abundance of OsMT1e-P in a developmental and organ specific manner. Using transgenic approach, we found a positive correlation between ectopic expression of OsMT1e-P and stress tolerance. Our experiments further suggest ROS scavenging to be the possible mechanism for multiple stress tolerance conferred by OsMT1e-P. CONCLUSION: We present an overview of MTs, describing their gene structure, genome localization and expression patterns under salinity and development in rice. We have found that ectopic expression of OsMT1e-P enhances tolerance towards multiple abiotic stresses in transgenic tobacco and the resultant plants could survive and set viable seeds under saline conditions. Taken together, the experiments presented here have indicated that ectopic expression of OsMT1e-P protects against oxidative stress primarily through efficient scavenging of reactive oxygen species. PMID- 22780877 TI - BCL-2 family of proteins and mammary cellular fate. AB - This review focuses on the pro-apoptotic and anti-apoptotic Bcl-2 family members involved in apoptosis, which is the predominant process controlling cell remodelling during post-lactational mammary gland involution. The members of the Bcl-2 protein family, whose expression levels are under the control of lactogenic hormones, internally control this mechanism also during lactation. They can physically interact with each other, sometimes in an antagonistic manner. Mammary glands undergo repeated cycles of structural development, functional differentiation and regression, therefore provide a unique model for investigating this family of proteins that regulate the fate of the secretory cells and consequently milk yield. The involvement of Bcl-2 family members is reviewed in mammary tissue during morphogenesis, at different stages of lactation cycle and in comparison with dairy and laboratory animals. PMID- 22780878 TI - Retrograde tracing with fluorescent microspheres reveals bifurcating projections from central retina to tectum and thalamus in chicks. AB - The goal of this study is to demonstrate the dual-projection pattern of retinal ganglion cells (RGCs) projecting to the tectum and visual thalamus in chick using retrograde fluorescent tracers and also to define the morphological properties of these RGCs with dual projections by intracellular injection of Lucifer Yellow (LY) combined with immunohistochemistry. Thirty-two chicks received double injections of green and red fluorescent microspheres into their thalamus and tectum in the same side. In the central retina, most of the labelled RGCs were tec-RGCs (RGCs projecting to the tectum), a quarter was tha-RGCs (RGCs projecting to the thalamus), and almost all of the tha-RGCs were double-labelled RGCs. An intracellular injection of LY into the double-labelled RGCs showed all six groups of RGCs without specific populations in each group (J. Comp. Neurol., 2004, 469: 360). These dendritic patterns were mostly mono- and bistrata, which extended horizontally in the deeper part of the inner plexiform layer. PMID- 22780879 TI - Identification of gonadal tissue in cryptorchid stallion can be improved by molecular biological analysis - a case report. AB - Surgically removed testicular tissue in cryptorchid stallions is sometimes difficult to identify because of morphological and histological malformation. Therefore, a sure method to characterise the removed tissue is required. A 2-year old Haflinger stallion was castrated after diagnosis of cryptorchidism to remove the left intra-abdomnial testis. Intra-operative exploration of the abdominal cavity revealed a firm, dysmorphic structure, which could not be identified as testis based on macroscopic anatomy. The removed tissue was Bouin-fixed and paraffin-embedded for histological examination. We additionally applied immuno histochemistry for smooth muscle actin to identify tubular structures as well as reverse transcriptase polymerase chain reaction (RT-PCR) to detect the expression of steroidogenic acute regulatory protein (StAR), indicating the presence of Leydig cells. A hCG test was conducted after surgery to screen for remaining testicular tissue. Histological examination using haematoxylin and eosin staining revealed signs of tissue calcification, amorph matrix with scattered cells and round structures. The latter could not be definitely identified as tubules. Actin staining revealed a few tubular wall structures. StAR mRNA expression indicated the presence of Leydig cells in parts of the removed tissue. The hCG test after castration showed no increase in testosterone. Histological and molecular biological examination of extirpated tissue in cryptorchid stallions can play an important role in the identification of the malformed testes like structures. The use of molecular biological techniques provides the opportunity to characterise surgically removed abdominal tissue that cannot be clearly diagnosed by routine histological examination. PMID- 22780880 TI - Transition-state metal aryl bond stability determines regioselectivity in palladium acetate mediated C-H bond activation of heteroarenes. AB - Density functional calculations reveal that the stability of developing metal aryl bonds in Pd(II)-acetate C-H activation transition states determines regioselectivity in arene and heteroarene compounds. This kinetic-thermodynamic connection explains the general preference for activation of the strongest C-H bond and provides the possibility for regioselectivity prediction. PMID- 22780881 TI - Critical effect of peptide cyclization on the potency of peptide inhibitors against Dengue virus NS2B-NS3 protease. AB - Dengue virus (DENV) infection is a serious public health threat worldwide that demands effective treatment. In the search for potent virus protease inhibitors, several cone snail venoms were screened against serotype 2 DENV NS2B-NS3 protease, and one conotoxin, MrIA, was identified to have inhibitory activity. The inhibitory activity was attributed to a disulfide bond-mediated loop, from which rational optimization was made to improve the potency and stability. An eight-residue cyclic peptide inhibitor was finally obtained with high potency (inhibitory constant 2.2 MUM), stability, and cell permeability. This inhibitor can thus serve as a good lead for DENV drug development. In addition, this work highlights the critical effect of peptide cyclization on the potency of oligopeptide inhibitors against DENV protease, which may advance the design of peptide inhibitors for homologous virus proteases. PMID- 22780882 TI - Nuclear markers reveal a complex introgression pattern among marine turtle species on the Brazilian coast. AB - Surprisingly, a high frequency of interspecific sea turtle hybrids has been previously recorded in a nesting site along a short stretch of the Brazilian coast. Mitochondrial DNA data indicated that as much as 43% of the females identified as Eretmochelys imbricata are hybrids in this area (Bahia State of Brazil). It is a remarkable find, because most of the nesting sites surveyed worldwide, including some in northern Brazil, presents no hybrids, and rare Caribbean sites present no more than 2% of hybrids. Thus, a detailed understanding of the hybridization process is needed to evaluate natural or anthropogenic causes of this regional phenomenon in Brazil, which could be an important factor affecting the conservation of this population. We analysed a set of 12 nuclear markers to investigate the pattern of hybridization involving three species of sea turtles: hawksbill (E. imbricata), loggerhead (Caretta caretta) and olive ridley (Lepidochelys olivacea). Our data indicate that most of the individuals in the crossings L. olivacea * E. imbricata and L. olivacea * C. caretta are F1 hybrids, whereas C. caretta * E. imbricata crossings present F1 and backcrosses with both parental species. In addition, the C. caretta * E. imbricata hybridization seems to be gender and species biased, and we also found one individual with evidence of multispecies hybridization among C. caretta * E. imbricata * Chelonia mydas. The overall results also indicate that hybridization in this area is a recent phenomenon, spanning at least two generations or ~40 years. PMID- 22780883 TI - Opioid genetics: the key to personalized pain control? AB - There are now several strong opioids available to choose from for the relief of moderate to severe pain. On a population level, there is no difference in terms of analgesic efficacy or adverse reactions between these drugs; however, on an individual level there is marked variation in response to a given opioid. The genetic influences to this variation are complex, and although current research has shown some promising results, these have not been replicated across larger studies and as such the ultimate aim of personalized prescribing remains elusive. If personalized prescribing could be achieved this would have a major impact at an individual level to facilitate safe, effective and rapid symptom control. This review presents some of the recent positive advances in opioid pharmacogenetic studies, focusing on associations between candidate genes and the three main elements of opioid response: analgesic, upper gastrointestinal and central adverse reactions. PMID- 22780886 TI - Identification of differentially expressed genes associated with changes in the morphology of Pichia fermentans on apple and peach fruit. AB - Pichia fermentans (strain DISAABA 726) is an effective biocontrol agent against Monilinia fructicola and Botrytis cinerea when inoculated in artificially wounded apple fruit but is an aggressive pathogen when inoculated on wounded peach fruit, causing severe fruit decay. Pichia fermentans grows as budding yeast on apple tissue and exhibits pseudohyphal growth on peach tissue, suggesting that dimorphism may be associated with pathogenicity. Two complementary suppressive subtractive hybridization (SSH) strategies, that is, rapid subtraction hybridization (RaSH) and PCR-based subtraction, were performed to identify genes differentially expressed by P. fermentans after 24-h growth on apple vs. peach fruit. Gene products that were more highly expressed on peach than on apple tissue, or vice versa, were sequenced and compared with available yeast genome sequence databases. Several of the genes more highly expressed, when P. fermentans was grown on peach, were related to stress response, glycolysis, amino acid metabolism, and alcoholic fermentation but surprisingly not to cell wall degrading enzymes such as pectinases or cellulases. The dual activity of P. fermentans as both a biocontrol agent and a pathogen emphasizes the need for a thorough risk analysis of potential antagonists to avoid unpredictable results that could negatively impact the safe use of postharvest biocontrol strategies. PMID- 22780885 TI - Therapeutic implications of vitamin D and calcium in overweight women with polycystic ovary syndrome. AB - OBJECTIVE: To assess effects of vitamin D and Calcium (Ca) on hormonal and metabolic milieu of polycystic ovary syndrome (PCOS). DESIGN: Single arm open label trial. METHODS: Twelve overweight and vitamin D deficient women with PCOS underwent a 2 hour oral glucose tolerance testing at baseline and following 3 month supplementation with vitamin D (daily dose of 3533 IU, increased to 8533 IU after the first five participants) and 530 mg elemental Ca daily. MAIN OUTCOME MEASURES: Blood pressure (BP), plasma glucose, insulin, total testosterone (T) androstenedione (A), sex hormone binding globulin, lifestyle parameters were assessed at baseline and following 3-month intervention. Insulin resistance (IR) and area under the curve for glucose and insulin were computed; paired analyses were conducted. RESULTS: Improved serum 25OHD (p < 0.001) and reductions in total T (p = 0.036) and A (p = 0.090) levels were noted following 3-month supplementation, compared to baseline. Significant lowering in BP parameters was seen in participants with baseline BP >= 120/80 mmHg (n = 8) and in those with baseline serum 25OHD <=20 ng/ml (n = 9). Parameters of glucose homeostasis and IR remained unchanged (p > 0.05). CONCLUSIONS: Androgen and BP profiles improved followed three month intervention, suggesting therapeutic implications of vitamin D and Ca in overweight and vitamin D deficient women with PCOS. PMID- 22780884 TI - Reduction in delayed mortality and subtle improvement in retrograde memory performance in pilocarpine-treated mice with conditional neuronal deletion of cyclooxygenase-2 gene. AB - PURPOSE: Pilocarpine induces prolonged status epilepticus (SE) in rodents that results in neurodegeneration and cognitive deficits, both commonly observed to be associated with human temporal lobe epilepsy. The multifunctional neuronal modulator, cyclooxygenase-2 (PTGS2 or COX-2), is rapidly induced after SE, mainly in principal neurons of the hippocampal formation and cortex. We used mice in which COX-2 is conditionally ablated in principal forebrain neurons to investigate the involvement of neuron-derived COX-2 in delayed mortality and performance in the Barnes maze. METHODS: Using the COX-2 conditional knockout mouse (nCOX-2 cKO) and their littermate wild-type controls, we compared motor behavior and performance in the Barnes maze before and 3 weeks after the induction of SE by pilocarpine. Mortality rate was also measured during SE and in the week following SE. KEY FINDINGS: nCOX-2 cKO mice showed less delayed mortality than wild-type mice in the week after SE. Although motor behavior and most cognitive measures were not different in the nCOX-2 cKO, upon reexposure to the maze 3 weeks after pilocarpine, the latency to find the previously learned target hole was significantly shorter in the nCOX-2 cKO than their wild-type littermate controls. By this measure pilocarpine-treated nCOX-2 cKO mice were identical to mice that had not experienced SE. SIGNIFICANCE: Results point to a role for neuronal COX-2 in delayed mortality in mice during the week following SE and suggest that neuronal COX-2 contributes to selected cognitive deficits observed after SE. Taking into consideration our previous findings that neurodegeneration and neuroinflammation after SE are reduced in the nCOX-2 cKO, and opening of the blood-brain barrier after pilocarpine is prevented, we conclude that neuronal COX-2 induction is an early step in many of the deleterious consequences of SE. PMID- 22780887 TI - Point group symmetry determination via observables revealed by polarized second harmonic generation microscopy: (2) applications. AB - In this work, the theory presented in part 1 (van der Veen, M. A.; Vermoortele, F.; De Vos, D. E.; Verbiest, T. Anal. Chem. 2012, DOI: 10.1021/ac300936q) for determination of the point groups symmetry based on easily distinguishable observables present in simple polarization dependent tests in second harmonic generation microscopy is tested. It is shown experimentally that the methodology can be applied for point group symmetry determination for a variety of structures among which molecular crystals and host/guest systems where the symmetry of the guest molecules cannot be inferred from conventional diffraction methods. Uniquely, this second-harmonic generation based method can discriminate between chiral and achiral structures regardless of their orientation. The method allows for in situ and in vivo studies with spatial resolution. PMID- 22780888 TI - Poly(ionic liquid) complex with spontaneous micro-/mesoporosity: template-free synthesis and application as catalyst support. AB - A facile, template-free synthetic route is reported toward poly(ionic liquid) complexes (PILCs) which for the first time exhibit stable micro-/mesoporous structure. This is accomplished via in situ ionic complexation between imidazolium-based PILs and poly(acrylic acid) in various alkaline organic solvents. The PILC can be highly loaded with copper salts and can be used as a catalytic support for effective aerobic oxidation of activated hydrocarbons under mild conditions. PMID- 22780890 TI - Nitric oxide, hemolysis, and the red blood cell storage lesion: interactions between transfusion, donor, and recipient. PMID- 22780891 TI - Would it be possible to prevent HPA-1a alloimmunization to reduce the incidence of fetal and neonatal alloimmune thrombocytopenia? PMID- 22780893 TI - Transfusion-transmitted babesiosis: achieving successful mitigation while balancing cost and donor loss. PMID- 22780892 TI - Human parvovirus 4 in the blood supply and transmission by pooled plasma-derived clotting factors: does it matter? PMID- 22780894 TI - Transfusion medicine illustrated. Massive hemolysis due to thrombotic thrombocytopenic purpura in a patient with AIDS. PMID- 22780896 TI - A seasonal association of incident cases of thrombotic thrombocytopenic purpura was not observed in the Oklahoma TTP-HUS Registry. PMID- 22780898 TI - Transfusion of older blood and risk of death: unanswered questions. PMID- 22780899 TI - Posttransfusion red blood cell (RBC) survival determined using biotin-labeled RBCs has distinct advantages over labeling with (51) Cr. PMID- 22780901 TI - Assessing causality in the transmission of viruses by blood products. PMID- 22780902 TI - Preparing for aging among older villagers in northeastern Thailand. AB - In the present study, we examined how older people prepared themselves in older age, by drawing on data from a qualitative study conducted in an urban area in Khon Kaen province, Thailand. Data were collected using observations, natural interviews, and in-depth interviews with 35 older people, concurrently analyzed using thematic analysis. Preparation for aging, from their perspectives, consisted of attending to their physical health, spiritual well-being, and preparing for death. The degree and quality of aging preparation was influenced by life events, personal health status, and family economic status. People actively prepare themselves for aging, and this appears to help them as they encounter life difficulties during their old age. Lifelong preparation strategies need to be studied further, so that locally-appropriate strategies of health care can be implemented for older people. PMID- 22780903 TI - Willingness of Lebanese physicians in the United States to relocate to Lebanon. AB - BACKGROUND: We recently proposed that Lebanon could become a regional 'academic hub' through the repatriation of emigrated Lebanese physicians who would then provide clinical services in the Arab Gulf region on a locum tenens basis. The objectives of this study were to assess the willingness of Lebanese medical graduates practicing in the United States of America to relocate to Lebanon and the Arab Gulf region and to explore the factors associated with this willingness. METHODS: In 2009 we surveyed Lebanese medical graduates practicing medicine in the United States. The questionnaire included questions about their willingness to relocate to Lebanon and to the Arab Gulf region and the associated timeframes. The questionnaire also included questions about family factors. We linked responders' answers to their personal, educational, and practice characteristics provided by the American Medical Association Physicians' Dataset. We conducted both descriptive and regression analyses. RESULTS: A total of 286 physicians participated in the survey (57% response rate). A majority (61%) was willing to relocate to Lebanon (51% possibly, 10% definitely). A third (33%) were willing to relocate to the Arab Gulf region (31% possibly, 2% definitely). About half (54%) were willing to relocate to Lebanon as a base for clinical missions to the Arab Gulf region (49% possibly, 5% definitely). Willingness to relocate to Lebanon was independently associated with Lebanese citizenship and the birthplace of the spouse being Lebanon, and inversely associated with US citizenship. Willingness to relocate to the Arab Gulf region was independently associated with being board certified, and inversely associated with being married, the age of the oldest child, and practicing in direct patient care. Willingness to relocate to Lebanon as a base was not independently associated with any factor. CONCLUSIONS: The findings of this study support the feasibility of the proposal of Lebanon becoming a regional 'academic hub'. Future research should explore other factors important for the feasibility of the proposal as well as actual relocation. PMID- 22780905 TI - Donor-substituted octacyano[4]dendralenes: investigation of pi-electron delocalization in their radical ions. AB - Symmetrically and unsymmetrically electron-donor-substituted octacyano[4]dendralenes were synthesized and their opto-electronic properties investigated by UV/vis spectroscopy, electrochemical measurements (cyclic voltammetry (CV) and rotating disk voltammetry (RDV)), and electron paramagnetic resonance (EPR) spectroscopy. These nonplanar push-pull chromophores are potent electron acceptors, featuring potentials for first reversible electron uptake around at -0.1 V (vs Fc(+)/Fc, in CH2Cl2 + 0.1 M n-Bu4NPF6) and, in one case, a remarkably small HOMO-LUMO gap (DeltaE = 0.68 V). EPR measurements gave well resolved spectra after one-electron reduction of the octacyano[4]dendralenes, whereas the one-electron oxidized species could not be detected in all cases. Investigations of the radical anions of related donor-substituted 1,1,4,4 tetracyanobuta-1,3-diene derivatives revealed electron localization at one 1,1 dicyanovinyl (DCV) moiety, in contrast to predictions by density functional theory (DFT) calculations. The particular factors leading to the charge distribution in the electron-accepting domains of the tetracyano and octacyano chromophores are discussed. PMID- 22780906 TI - Micellar delivery of cyclopamine and gefitinib for treating pancreatic cancer. AB - Hedgehog (Hh) and epidermal growth factor receptor (EGFR) signaling are involved in pancreatic cancer progression. Targeting these pathways simultaneously with cyclopamine (Hh inhibitor) and gefitinib (EGFR inhibitor) is a promising approach for treating pancreatic cancer. However, the major limitation for effective clinical translation of these molecules is their low aqueous solubility. We have previously demonstrated that methoxy polyethyleneglycol-b-poly(carbonate-co lactic acid) {mPEG-b-P(CB-co-LA)} copolymer solubilizes hydrophobic anticancer drugs and has the potential to deliver to tumors by an enhanced permeability and retention (EPR) effect. In this study, using the nanoprecipitation method, cyclopamine and gefitinib were efficiently loaded into mPEG-b-P(CB-co-LA) micelles with encapsulation efficiencies of 94.4 and 88.6%, respectively. These micelles had a narrow particle size distribution with a mean particle size of 54.3 nm and a PDI of 0.14. Combination therapy showed a synergistic effect against L3.6pl cells but an additive effect against MIA PaCa-2 cells. Caspase 3/7 activity was also increased when this combination therapy was used, indicating apoptotic cell death. Gene and protein expression analysis indicated cross-talk between Hh and EGFR signaling. Furthermore, the combination decreased tumor growth rate in L3.6pl-derived xenograft mouse tumors. These data suggest the applicability of our micellar system to effectively load and deliver cyclopamine and gefitinib for combination chemotherapy. PMID- 22780907 TI - Black box optimization benchmarking of the GLOBAL method. AB - GLOBAL is a multi-start type stochastic method for bound constrained global optimization problems. Its goal is to find the best local minima that are potentially global. For this reason it involves a combination of sampling, clustering, and local search. The role of clustering is to reduce the number of local searches by forming groups of points around the local minimizers from a uniformly sampled domain and to start few local searches in each of those groups. We evaluate the performance of the GLOBAL algorithm on the BBOB 2009 noiseless testbed, containing problems which reflect the typical difficulties arising in real-world applications. The obtained results are also compared with those obtained form the simple multi-start procedure in order to analyze the effects of the applied clustering rule. An improved parameterization is introduced in the GLOBAL method and the performance of the new procedure is compared with the performance of the MATLAB GlobalSearch solver by using the BBOB 2010 test environment. PMID- 22780904 TI - Mycobacterium tuberculosis WhiB4 regulates oxidative stress response to modulate survival and dissemination in vivo. AB - Host-generated oxidative stress is considered one of the main mechanisms constraining Mycobacterium tuberculosis (Mtb) growth. The redox-sensing mechanisms in Mtb are not completely understood. Here we show that WhiB4 responds to oxygen (O2) and nitric oxide (NO) via its 4Fe-4S cluster and controls the oxidative stress response in Mtb. The WhiB4 mutant (MtbDeltawhiB4) displayed an altered redox balance and a reduced membrane potential. Microarray analysis demonstrated that MtbDeltawhiB4 overexpresses the antioxidant systems including alkyl hydroperoxidase (ahpC-ahpD) and rubredoxins (rubA-rubB). DNA binding assays showed that WhiB4 [4Fe-4S] cluster is dispensable for DNA binding. However, oxidation of the apo-WhiB4 Cys thiols induced disulphide-linked oligomerization, DNA binding and transcriptional repression, whereas reduction reversed the effect. Furthermore, WhiB4 binds DNA with a preference for GC-rich sequences. Expression analysis showed that oxidative stress repressed whiB4 and induced antioxidants in Mtb, while their hyper-induction was observed in MtbDeltawhiB4. MtbDeltawhiB4 showed increased resistance to oxidative stress in vitro and enhanced survival inside the macrophages. Lastly, MtbDeltawhiB4 displayed hypervirulence in the lungs of guinea pigs, but showed a defect in dissemination to their spleen. These findings suggest that WhiB4 systematically calibrates the activation of oxidative stress response in Mtb to maintain redox balance, and to modulate virulence. PMID- 22780908 TI - Past and future trends in cancer and biomedical research: a comparison between Egypt and the world using PubMed-indexed publications. AB - BACKGROUND: PubMed is a free web literature search service that contains almost 21 millions of abstracts and publications with almost 5 million user queries daily. The purposes of the study were to compare trends in PubMed-indexed cancer and biomedical publications from Egypt to that of the world and to predict future publication volumes. METHODS: The PubMed was searched for the biomedical publications between 1991 and 2010 (publications dates). Affiliation was then limited to Egypt. Further limitation was applied to cancer, human and animal publications. Poisson regression model was used for prediction of future number of publications between 2011 and 2020. RESULTS: Cancer publications contributed 23% to biomedical publications both for Egypt and the world. Egyptian biomedical and cancer publications contributed about 0.13% to their world counterparts. This contribution was more than doubled over the study period. Egyptian and world's publications increased from year to year with rapid rise starting the year 2003. Egyptian as well as world's human cancer publications showed the highest increases. Egyptian publications had some peculiarities; they showed some drop at the years 1994 and 2002 and apart from the decline in the animal: human ratio with time, all Egyptian publications in the period 1991-2000 were significantly more than those in 2001-2010 (P < 0.05 for all). By 2020, Egyptian biomedical and cancer publications will increase by 158.7% and 280% relative to 2010 to constitute 0.34% and 0.17% of total PubMed publications, respectively. CONCLUSIONS: The Egyptian contribution to world's biomedical and cancer publications needs significant improvements through research strategic planning, setting national research priorities, adequate funding and researchers' training. PMID- 22780909 TI - Free energetics of carbon nanotube association in pure and aqueous ionic solutions. AB - Carbon nanotubes are a promising platform across a broad spectrum of applications ranging from separations technology, drug delivery, to bio(electronic) sensors. Proper dispersion of carbon nanotube materials is important to retaining the electronic properties of nanotubes. Experimentally it has been shown that salts can regulate the dispersing properties of CNTs in aqueous system with surfactants (Niyogi, S.; Densmore, C. G.; Doorn, S. K. J. Am. Chem. Soc.2009, 131, 1144 1153); details of the physicochemical mechanisms underlying such effects continue to be explored. We address the effects of inorganic monovalent salts (NaCl and NaI) on dispersion stability of carbon nanotubes.We perform all-atom molecular dynamics simulations using nonpolarizable interaction models to compute the potential of mean force between two (10,10) single-walled carbon nanotubes (SWNTs) in the presence of NaCl/NaI and compare to the potential of mean force between SWNTs in pure water. Addition of salts enhances stability of the contact state between two SWNT's on the order of 4 kcal/mol. The ion-specific spatial distribution of different halide anions gives rise to starkly different contributions to the free energy stability of nanotubes in the contact state. Iodide anion directly stabilizes the contact state to a much greater extent than chloride anion. The enhanced stability arises from the locally repulsive forces imposed on nanotubes by the surface-segregated iodide anion. Within the time scale of our simulations, both NaI and NaCl solutions stabilize the contact state by equivalent amounts. The marginally higher stability for contact state in salt solutions recapitulates results for small hydrophobic solutes in NaCl solutions (Athawale, M. V.; Sarupria, S.; Garde, S. J. Phys. Chem. B2008, 112, 5661-5670) as well as single-walled carbon nanotubes in NaCl and CaCl2 aqueous solutions. PMID- 22780910 TI - The psychological benefits of recreational running: a field study. AB - Running yields positive changes in affect, but the external validity of controlled studies has received little attention in the literature. In this inquiry, 50 recreational runners completed the Exercise-Induced Feeling Inventory (Gauvin & Rejeski, 1993) before and after a bout of self-planned running on an urban running path. Positive changes were seen in all four measures of affect (p < .001). Multivariate regressions were performed to examine the contribution of four exercise characteristics (i.e., duration of the current run, weekly running time, weekly running distance, and running experience) to the observed changes in affect. The results have revealed that exercise characteristics accounted for only 14-30% of the variance in the recreational runners' affect, in both directions. It is concluded that psychological benefits of recreational running may be linked to placebo (conditioning and/or expectancy) effects. PMID- 22780911 TI - Effect of dental implant diameter on fatigue performance. Part I: mechanical behavior. AB - AIM: The purpose of this study was to evaluate the effect of the implants' diameter on the mechanical function and load-fatigue performance of dental implants. MATERIALS AND METHODS: Three groups of implants with different diameters (3.3 mm, 3.75 mm and 5 mm), were tested under static and cyclic compressive loading. A total number of 15 implants for the static test and 112 implants for the cyclic-fatigue test. In the cyclic test, the machine ceased operating when the structure collapsed or when it reached 5 * 10(6) cycles without apparent failure. The load versus the number of cycles was plotted as curves for biomechanical analysis (S-N curve) for each implant diameter. RESULTS: The S-N curve plotted for the 5 mm implants showed classic fatigue behavior with a finite life region starting from 620N. The same was observed for the 3.75 mm diameter implants, with a finite life region starting below 620N. By contrast, the 3.3 mm diameter implants failed to show predictable fatigue behavior and a fatigue limit could not be defined. CONCLUSIONS: The results of this study emphasize the importance of implant diameter on fatigue behavior. Narrow implants failed to show typical fatigue behavior which might be attributed to the implant design. PMID- 22780912 TI - Polymer blend microspheres for controlled drug release: the techniques for preparation and characterization: a review article. AB - The use of polymers and their microspheres in drug delivery is well known for they are being widely used in the field of drug delivery. The polymer entraps a drug which is to be released in a predesigned manner in the body through biodegradation. The blending of polymers is one way of modifying and enhancing the properties of polymer- based products which is also a cost effective procedure rather than developing a new product. The molecular weight of the polymer, the composition of the blend, the sphere porosity and size, and drug distribution are found to be controllable factors on which drug delivery depends. Polymer blends are obtained by allowing two polymers to combine as one material which has the advantage of two or more polymers. Polymer microspheres are small spherical particles with diameters in the micrometer range between 1MUm to 1000MUm which are manufactured from various natural and synthetic materials. Microspheres are used to administer medication in a rate- controlled manner and sometimes in a targeted manner. This review presents various polymer blend- combinations in different ratios, the different processing techniques adopted and the details of their characterization through examples found in a literature survey. The characterization of the different polymer blends or microspheres showed changes in structure, increase in drug loading, encapsulation efficiency, biocompatibility and low cytotoxicity. PMID- 22780913 TI - Automated solid-phase synthesis of hyaluronan oligosaccharides. AB - Well-defined fragments of hyaluronic acid (HA) have been obtained through a fully automated solid-phase oligosaccharide synthesis. Disaccharide building blocks, featuring a disarmed glucuronic acid donor moiety and a di-tert-butylsilylidene protected glucosamine part, were used in the rapid and efficient assembly of HA fragments up to the pentadecamer level, equipped with a conjugation-ready anomeric allyl function. PMID- 22780914 TI - Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3 yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disorders. AB - 6-[(3S,4S)-4-Methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943) is a novel PDE9A inhibitor identified using parallel synthetic chemistry and structure based drug design (SBDD) and has advanced into clinical trials. Selectivity for PDE9A over other PDE family members was achieved by targeting key residue differences between the PDE9A and PDE1C catalytic site. The physicochemical properties of the series were optimized to provide excellent in vitro and in vivo pharmacokinetics properties in multiple species including humans. It has been reported to elevate central cGMP levels in the brain and CSF of rodents. In addition, it exhibits procognitive activity in several rodent models and synaptic stabilization in an amyloid precursor protein (APP) transgenic mouse model. Recent disclosures from clinical trials confirm that it is well tolerated in humans and elevates cGMP in cerebral spinal fluid of healthy volunteers, confirming that it is a quality pharmacological tool for testing clinical hypotheses in disease states associated with impairment of cGMP signaling or cognition. PMID- 22780915 TI - A novel multiplex polymerase chain reaction assay for profile analyses of gene expression in peripheral blood. AB - BACKGROUND: Studies have demonstrated that inflammation has a key role in the pathogenesis of atherosclerosis due to the abnormal gene expressions of multiple cytokines. We established an accurate and precise method to observe gene expression in whole blood that might provide specific diagnostic information for coronary artery disease (CAD) and other related diseases. METHODS: The fifteen selected CAD-related genes (IL1B, IL6, IL8, IFNG, MCP-1, VWF, MTHFR, SELL, TNFalpha, ubiquitin, MCSF, ICAM1, ID2, HMOX1 and LDLR) and two housekeeping genes (ACTB and GK) as internal references have been measured simultaneously with a newly developed multiplex polymerase chain reaction (multi-PCR) method. Moreover, the precision was evaluated, and a procedure for distinguishing patients from the normal population has been developed based upon analyses of peripheral blood. A total of 148 subjects were divided into group A (control group without plaques), group B (calcified plaques) and group C (non-calcified plaques, and combination group) according dual-source CT criteria. Gene expression in blood was analyzed by multi-PCR, and levels of glucose and lipids measured in 50 subjects to explore the relationship among them. RESULTS: The precision results of the multi-PCR system revealed within-run and between-run CV values of 3.695-12.537% and 4.405 13.405%, respectively. The profiles of cytokine gene expression in peripheral blood were set: a positive correlation between glucose and MCSF, HMOX1 or TNFalpha were found. We also found that triglyceride levels were negatively correlated with SELL gene expression in 50 subjects. Compared with controls, gene expression levels of IL1B, IL6, IL8 and MCP-1 increased significantly in group C. CONCLUSIONS: A new multiple gene expression analysis system has been developed. The primary data suggested that gene expression was related to CAD. This system might be used for risk assessment of CVDs and other related diseases. PMID- 22780916 TI - Sleep disorders in children after treatment for a CNS tumour. AB - The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with clinical characteristics and daily performance (fatigue and psychosocial functioning). In a cross-sectional study at the outpatient clinic of the Emma Children's Hospital AMC (February-June 2010), sleep, fatigue and psychosocial functioning were analysed in 31 CNS tumour patients (mean age: 11.8years; 20 boys) and compared with 78 patients treated for a non-CNS malignancy (mean age: 9.7years; 41 boys) and norm data. Questionnaires applied were the Sleep Disorder Scale for Children, the Epworth Sleepiness Scale, the Pediatric Quality of Life Inventory, and the Strengths and Difficulties Questionnaire. Sleeping habits and endocrine deficiencies were assessed with a self-developed questionnaire. Increased somnolence was found in CNS tumour patients compared with those with a non-CNS malignancy (8.8+/-2.8 versus 7.5+/-2.7; P<0.05). Both patient groups reported more problems (P<0.01) than the norm with initiating and maintaining sleep. No specific risk factors were identified for a sleep disorder in CNS tumour patients, but their excessive somnolence was correlated with lower fatigue related quality of life (QoL) (r=-0.78, P<0.001) and worse psychosocial functioning (r=0.63, P<0.001). In conclusion, children treated for a CNS tumour have increased somnolence, significantly increasing fatigue and worsening daily functioning. Further investigation should focus on possibilities to improve sleep quality and diminish fatigue. PMID- 22780917 TI - Familial focal epilepsy with variable foci mapped to chromosome 22q12: expansion of the phenotypic spectrum. AB - We aimed to refine the phenotypic spectrum and map the causative gene in two families with familial focal epilepsy with variable foci (FFEVF). A new five generation Australian FFEVF family (A) underwent electroclinical phenotyping, and the original four-generation Australian FFEVF family (B) (Ann Neurol, 44, 1998, 890) was re-analyzed, including new affected individuals. Mapping studies examined segregation at the chromosome 22q12 FFEVF region. In family B, the original whole genome microsatellite data was reviewed. Five subjects in family A and 10 in family B had FFEVF with predominantly awake attacks and active EEG studies with a different phenotypic picture from other families. In family B, reanalysis excluded the tentative 2q locus reported. Both families mapped to chromosome 22q12. Our results confirm chromosome 22q12 as the solitary locus for FFEVF. Both families show a subtly different phenotype to other published families extending the clinical spectrum of FFEVF. PMID- 22780918 TI - Nutritional requirements of the BY series of Saccharomyces cerevisiae strains for optimum growth. AB - Among the vast variety of Saccharomyces cerevisiae strains, the BY family is particularly important because the widely used deletion collections are based on this background. Here we demonstrate that some standard growth media recipes require substantial modifications to provide optimum growth conditions for auxotrophic BY strains and to avoid growth arrest before glucose is depleted. In addition to the essential supplements that are required to satisfy auxotrophic requirements, we found the four amino acids phenylalanine, glutamic acid, serine, and threonine to be indispensable for optimum growth, despite the fact that BY is 'prototrophic' for these amino acids. Interestingly, other widely used S. cerevisiae strains, such as strains of the CEN.PK family, are less sensitive to lack of the described supplements. Furthermore, we found that the concentration of inositol in yeast nitrogen base is too low to support fast proliferation of yeast cultures until glucose is exhausted. Depletion of inositol during exponential growth induces characteristic changes, namely a decrease in glucose uptake and maximum specific growth rate, increased cell size, reduced viability, and accumulation of lipid storage pools. Thus, several of the existing growth media recipes need to be revised to achieve optimum growth conditions for BY derived strains. PMID- 22780920 TI - Central respiratory drive in patients with neuromuscular diseases. AB - BACKGROUND: The contribution of the central respiratory drive in the hypercapnic respiratory failure of neuromuscular diseases (NMD) is controversial. OBJECTIVE: To compare the CO2 response and the duration of weaning of mechanical ventilation between a group of NMD patients and a group of quadriplegic patients due to ICU acquired weakness (ICU-AW). METHODS: We prospectively studied 16 subjects with NMD and 26 subjects with ICU-AW ready for weaning, using the method of the re inhalation of expired air. We measured the hypercapnic drive response, defined as the ratio of change in airway occlusion pressure 0.1 second after the start of inspiration (DeltaP0.1) to the change in Paco2 (DeltaPaco2), and the hypercapnic ventilatory response, defined as the ratio of the change in minute ventilation (DeltaVe) to DeltaPaco2. We considered a value of <= 0.19 cm H2O/mm Hg as reduced hypercapnic drive response. RESULTS: Hypercapnic drive response (DeltaP0.1/DeltaPaco2 = 0.14 +/- 0.08 cm H2O/mm Hg vs 0.37 +/- 0.27 cm H2O/mm Hg, P = .002) and hypercapnic ventilatory response (DeltaVe/DeltaPaco2 = 0.21 +/- 0.19 L/min/mm Hg vs 0.44 +/- 0.40 L/min/mm Hg, P = .02) were lower in the NMD than in the ICU-AW subjects. Duration of weaning values, according to the Kaplan Meier curves, were similar in both groups (Log-rank = 0.03, P = .96). Eleven NMD (69%) and 9 ICU-AW (35%) subjects had hypercapnic drive response <= 0.19 cm H2O/mm Hg. The duration of weaning was longer in subjects with hypercapnic drive response <= 0.19 cm H2O/mm Hg (log-rank = 15.4, P < .001). CONCLUSIONS: Subjects with acute hypercapnic respiratory failure due to NMD had reduced hypercapnic drive response, compared to ICU-AW subjects. The duration of weaning was longer in subjects with reduced hypercapnic drive response. PMID- 22780919 TI - Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. AB - No curative treatment exists for glioblastoma, with median survival times of less than 2 years from diagnosis. As an approach to develop immune-based therapies for glioblastoma, we sought to target antigens expressed in glioma stem cells (GSCs). GSCs have multiple properties that make them significantly more representative of glioma tumors than established glioma cell lines. Epidermal growth factor receptor variant III (EGFRvIII) is the result of a novel tumor-specific gene rearrangement that produces a unique protein expressed in approximately 30% of gliomas, and is an ideal target for immunotherapy. Using PCR primers spanning the EGFRvIII-specific deletion, we found that this tumor-specific gene is expressed in three of three GCS lines. Based on the sequence information of seven EGFRvIII specific monoclonal antibodies (mAbs), we assembled chimeric antigen receptors (CARs) and evaluated the ability of CAR-engineered T cells to recognize EGFRvIII. Three of these anti-EGFRvIII CAR-engineered T cells produced the effector cytokine, interferon-gamma, and lysed antigen-expressing target cells. We concentrated development on a CAR produced from human mAb 139, which specifically recognized GSC lines and glioma cell lines expressing mutant EGFRvIII, but not wild-type EGFR and did not recognize any normal human cell tested. Using the 139 based CAR, T cells from glioblastoma patients could be genetically engineered to recognize EGFRvIII-expressing tumors and could be expanded ex vivo to large numbers, and maintained their antitumor activity. Based on these observations, a gamma-retroviral vector expressing this EGFRvIII CAR was produced for clinical application. PMID- 22780921 TI - Maintenance of efficacy of lisdexamfetamine dimesylate in adults with attention deficit/hyperactivity disorder: randomized withdrawal design. AB - OBJECTIVE: To evaluate lisdexamfetamine dimesylate maintenance of efficacy in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Adults (aged 18-55 years) who had ADHD meeting DSM-IV-TR criteria, baseline ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts total scores of < 22, and Clinical Global Impressions-Severity of Illness (CGI-S) ratings of 1, 2, or 3 were enrolled. After previously receiving commercially available lisdexamfetamine dimesylate (30, 50, or 70 mg/d) for >= 6 months with acceptable tolerability and maintaining response during a 3-week open-label phase at a stable lisdexamfetamine dimesylate dose, the participants entered a 6-week double-blind randomized withdrawal phase on treatment with lisdexamfetamine dimesylate (same dose) or placebo. Data were collected from April 2009 to July 2010. The primary outcome was the proportion of participants having symptom relapse (>= 50% increase in ADHD-RS-IV score and >= 2 rating-point increase in CGI-S score). RESULTS: A total of 116 participants were randomized (lisdexamfetamine dimesylate n = 56; placebo n = 60). At the randomized withdrawal phase baseline, mean (SD) ADHD-RS-IV scores for lisdexamfetamine dimesylate and placebo were 10.6 (4.96) and 10.6 (4.82), respectively. At endpoint, 8.9% (5/56) of adults taking lisdexamfetamine dimesylate and 75.0% (45/60) taking placebo (P < .0001) showed symptom relapse; most showed relapse after 1 and 2 weeks of the randomized withdrawal phase (4 and 0 adults taking lisdexamfetamine dimesylate, 26 and 10 taking placebo, respectively). During the randomized withdrawal phase, treatment-emergent adverse events were reported in 48.2% and 30.0% of participants in the lisdexamfetamine dimesylate and placebo groups, respectively. Treatment-emergent adverse events with incidence >= 5% in the lisdexamfetamine dimesylate and placebo groups were headache (14.3% and 5.0%), insomnia (5.4% and 5.0%), and upper respiratory tract infection (8.9% and 0%). CONCLUSIONS: In adults with ADHD on medium- to long-term treatment, lisdexamfetamine dimesylate demonstrated maintenance of efficacy vs placebo upon randomized withdrawal. A majority of patients given placebo showed symptom relapse by 2 weeks. The safety profile of lisdexamfetamine dimesylate was generally consistent with previous lisdexamfetamine dimesylate studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00877487. PMID- 22780922 TI - [Current status and future perspectives of interstitial 125I seed implantation treatment for malignant tumors]. PMID- 22780923 TI - [Effect of gefitinib on the migration of triple-negative breast cancer cell line MDA-MB-231 cells]. AB - OBJECTIVE: To investigate the effect of gefitinib on the migration of triple negative breast cancer cell line MDA-MB-231 cells. METHODS: Gefitinib was used in concentrations of 0 micromol/L, 0.1 micromol/L, 1 micromol/L, 10 micromol/L and 20 micromol/L, respectively. Phosphorylation levels of EGFR and Akt were analyzed by Western blot. The capability of migration was measured by scratch test and Boyden chamber assay. Microfilaments (cell skeleton ) remolding and polarization were evaluated by immunofluorescence microscopy. RESULTS: Comparing with the control group (0 micromol/L gefitinib), gefitinib effectively inhibited the phosphorylation of EGFR and its downstream key proteins, and the effect displayed an obvious dose-effect relationship. At 24 hours after wound scratch, the cell migration distance of each group with 0, 0.1, 1, 10, 20 micromol/L gefitinib was (36.3 +/- 4.0) microm, (30.3 +/- 3.8) microm, (26.8 +/- 3.3) microm, (17.0 +/- 2.6) microm, and (11.0 +/- 2.5) microm, respectively. At 3.5 hours after Boyden chamber assay, the cell count of each group with 0, 0.1, 1, 10, 20 micromol/L gefitinib was 69.2 +/- 7.0, 51.8 +/- 7.5, 43.8 +/- 8.7, 30.6 +/- 4.8, and 28.4 +/ 3.4, respectively. Compared with the control group (0 micromol/L gefitinib), gefitinib could significantly prolong the wound-healing time and decrease the migrating cell count (P < 0.05), and significantly inhibit the lamellipodium formation, cell skeleton remolding and changes of the cytoskeleton polarization. CONCLUSIONS: Gefitinib can reduce the migration capacity of triple-negative breast cancer cells through inhibiting phosphorylation of EGFR/PI3K/Akt pathway, suppressing the cell skeleton (microfilaments) remolding and changes of its polarization. PMID- 22780924 TI - [Construction of a new oncolytic virus oHSV2hGM-CSF and its anti-tumor effects]. AB - OBJECTIVE: The aim of this study was to construct a new oncolytic virus oHSV2hGM CSF and evaluate its oncolytic activity in vitro and in vivo in parallel with oHSV1hGM-CSF. METHODS: oHSV2hGM-CSF was a replication-competent, attenuated HSV2 based on the HG52 virus (an HSV2 strain). It was engineered to be specific for cancer by deletion of the viral genes ICP34.5 and ICP47 and insertion of the gene encoding hGM-CSF. To measure the in vitro killing effect of the virus, 15 human tumor cell lines (HeLa, Eca-109, PG, HepG2, SK/FU, CNE-2Z, PC-3, SK-OV3, A-549, 786-0, MCF-7, Hep-2, HT-29, SK-Mel-28, U87-MG) and mouse melanoma (B16R) cell line were seeded into 24-well plates and infected with viruses at MOI = 1 (multiplicity of infection, MOI), or left uninfected. The cells were harvested 24 and 48 hours post infection, and observed under the microscope. For animal studies, the oncolytic viruses were administered intratumorally (at 3-day interval) at a dose of 2.3 x 10(6) PFU (plaque forming unit, PFU) for three times when the tumor volume reached 7-8 mm3. The tumor volume was measured at 3-day intervals and animal survival was recorded. RESULTS: Both oHSV2hCM-CSFand oHSV1hGM-CSF induced widespread cytopathic effects at 24 h after infection. OHSV2hGM-CSF, by contrast, produced more plaques with a syncytial phenotype than oHSV1hGM-CSF. In the in vitro killing experiments for the cell lines HeLa, HepG2, SK-Mel-28, B16R and U87-MG, oHSV2hGM-CSF eradicated significantly more cells than oHSV1hGM-CSF under the same conditions. For the mouse experiments, it was observed that oHSV2hGM-CSF significantly inhibited the tumor growth. At 15 days after B16R tumor cells inoculation, the tumor volumes of the PBS, oHSV1hGCM-CSF and oHSV2hGM-CSF groups were (374.7 +/- 128.24) mm3, (128.23 +/- 45.32) mm3 (P < 0.05, vs. PBS group) or (10.06 +/- 5.1) mm3 (P < 0.01, vs. PBS group), respectively (mean +/- error). The long term therapeutic effect of oHSV2hGM-CSF on the B16R animal model was evaluated by recording animal survival over 110 days after tumor cells inoculation whereas all the mice in the PBS group died by day 22 (P < 0.01). The anti-tumor mechanism of the newly constructed oHSV2hGM-CSF against B16R cell tumor appeared to include the directly oncolytic activity and the induction of anti-tumor immunity to some degree. CONCLUSION: The findings of our study demonstrate that the newly constructed oHSV2hGM-CSF has potent anti tumor activity in vitro to many tumor cell lines and in vive to the transplanted B16R tumor models. PMID- 22780925 TI - [Antitumor effect of sphingosine kinase 1 inhibitor in combination with chemotherapy on SGC7901 gastric cancer cells in vitro]. AB - OBJECTIVE: To study the effect of the sphingosine kinase 1 (SphK1) inhibitor N,N dimethylsphingosine (DMS) in combination with chemotherapeutic drugs (DDP, 5-Fu, MMC) on the proliferation of gastric cancer cells (SGC7901) in vitro, and to evaluate whether SphK1 inhibitors could be used as synergetic agents in chemotherapy. METHODS: SGC7901 cells were incubated in vitro with DMS (1 micromol/L) and 5-Fu, DDP, MMC at different concentrations in combination or separately for 24 h. The effects on the growth and survival of SGC7901 cells were determined by MTT assay. The inhibition rates were assessed by response surface analysis and the interactive relationships between the combined drugs were evaluated on the basis of positive/negative values of the cross product coefficients in the response surface equation. RESULTS: The growth inhibition rate of the gastric cancer cells by treatment with DMS (1 micromol/L) was (10.23 +/- 0.74)%. The growth inhibition rates of the gastric cancer cells treated with 5-Fu (1, 5 and 25 microg/ml) for 24 h were (9.95 +/- 3.24)%, (21.04 +/- 2.19)%, and (45.49 +/- 3.60)%, respectively. The growth inhibition rates of the gastric cancer cells treated with DDP (0.5, 2.5 and 12.5 microg/ml) for 24 h were (9.38 +/- 0.79)%, (19.61 +/- 0.90)%, and (29.83 +/- 0.54)%, respectively. The growth inhibition rates of the gastric cancer cells treated with MMC (0.1, 0.5 and 2.5 microg/ml) for 24 h were (15.35 +/- 0.77)%, (24.72 +/- 0.83)%, and (30.68 +/- 0.28)%, respectively. There were significant differences among the inhibition rates caused by different concentrations of the drugs (P < 0.05). When 1 micromol/L DMS was used in combination with 5-Fu (1, 5, and 25 microg/ml) for 24 h, the growth inhibition rates of the cancer cells were (16.76 +/- 0.41)%, (27.28 +/- 0.29)% and (52.56 +/- 3.60)%, respectively. When 1 micromol/L DMS was used in combination with DDP (0.5, 2.5, and 12.5 microg/ml) for 24 h, the growth inhibition rates of the cancer cells were (15.35 +/- 0.86)%, (25.57 +/- 0.27)%, (36.37 +/- 0.51)%, respectively. When 1 micromol/L DMS was used in combination with MMC (0.1, 0.5, and 2.5 microg/ml) for 24 h, the growth inhibition rates of the cancer cells were (21.02 +/- 0.28)%, (32.10 +/- 0.27)%, (36.36 +/- 0.28)%, respectively. There were also significant differences among the growth inhibition rates caused by different concentrations of the drugs alone and in combination groups (P < 0.05). CONCLUSIONS: DMS can suppress the proliferation of SGC7901 cells in vitro, and there are evident synergetic effects when it is used in combination with chemotherapeutic drugs. The results of this study indicate that SphK1 inhibitors may become novel and promising chemotherapeutic sensitizers. PMID- 22780926 TI - [New compound NL-608 (a nutlin analog) induces apoptosis in human breast cancer MCF-7 cells]. AB - OBJECTIVE: To observe the effect of NL-608 (a nutlin analog) on apoptosis induction in human breast cancer MCF-7 cells in vitro, and investigate the relevant molecular mechanism. METHODS: The effect of NL-608 on proliferation of MCF-7 cells was determined by MTT assay. The apoptosis in MCF-7 cells was determined by flow cytometry with annexin V-FITC and PI. The activity of caspase 3, caspase 8 and caspase 9 was determined with caspase activity assay kit and Western blot, and the proteins of Fas and FasL were determined by Western blot. RESULTS: NL-608 showed a dose-dependent inhibitory effect on the proliferation of MCF-7 cells. It induced apoptosis in MCF-7 cells in a dose-dependent manner. The activity of caspase 3 and caspase 8 in MCF-7 cells was increased with the increasing concentration of NL-608, but caspase 9 had no changes. The proteins of Fas and FasL were increased in a dose-dependent manner. CONCLUSION: NL-608 induces apoptosis in MCF-7 cells in vitro through inducing caspase 3 activity and death receptor-mediated signal pathway. PMID- 22780927 TI - [Effect of Notch1 on cell cycle, apoptosis and migration of laryngeal squamous cell carninoma cell line Hep-2]. AB - OBJECTIVE: To investigate the effect of Notch1 on cell cycle, apoptosis and migration of laryngeal squamous cell carcinoma cell line Hep-2 and explore its possible molecular mechanism. METHODS: Hep-2 cells were divided into three groups: untreated group, empty vector group and Notch1 group. The effects of upregulation of Notch1 expression on cell proliferation, cell cycle and apoptosis were assessed by CCK-8 staining and flow cytometry, respectively, and effect of upregulation of Notch1 expression on cell migration of Hep-2 cells was studied using Boyden chamber assay, and further expression changes of genes related to cell proliferation, cell cycle, apoptosis and migration were detected by semi quantitative RT-PCR and Western blotting. RESULTS: Compared with the untreated group and empty vector group, cell proliferation of Hep-2 in the Notch1 group was significantly inhibited (P < 0.05). The results of flow cytometry revealed that the percentage of cells at G0/G1 phase in the Notch1 group was (70.43 +/- 1.36)%, significantly higher than the (46.39 +/- 1.19)% in the untreated group or (48.41 +/- 1.18)% in the empty vector group, and there was a significant difference among the three groups (P = 0.000). In addition, the percentage of apoptotic cells in the Notch1 group was (22.46 +/- 0.90)%, significantly higher than that in the untreated group [(5.77 +/- 0.37)%] or empty vector group [(6.09 +/- 0.20)%], with a significant difference among the three groups (P = 0.000). The results of Boyden chamber assay demonstrated that the number of cells migrated through membrane in the Notch1 group was evidently lower than that in the untreated group and empty vector group. Moreover, the results of semi quantitative RT-PCR and Western blotting showed that cell proliferation inhibition and cell cycle arrest were closely associated with downregulation of cyclin D1, cyclin E and CDK2 expressions and upregulation of p53 expression. In addition, upregulation of Notch1 expression mediated cell apoptosis was tightly related to upregulation of caspase 3/9 expressions and downregulation of Bcl-2, while the decrease of Hep-2 cell migration ability was obviously correlated with downregulation of MMP-2/-9 expressions. CONCLUSIONS: Notch1 signaling pathway may play a pivotal role in the occurrence and development of laryngeal squamous cell carcinoma. Further study may elucidate that Notchl signaling pathway may become a molecular target for therapy of laryngeal squamous cell carcinoma. PMID- 22780928 TI - [Analysis of the immunohistochemical subtypes and prognosis of primary diffuse large B cell lymphoma of the central nervous system]. AB - OBJECTIVE: To analyze the subtypes of primary diffuse large B cell lymphoma of the central nervous system (CNS DLBCL) and to explore the relationship between the subtype classification and prognosis. METHODS: Immunohistochemical staining was used to determine the expression of CD20, CD3, CD10, Bcl-6, Mum-1, CD5, Bcl 2, Ki-67, FOXP-1, GCET-1, BLIMP-1 and LMO-2 antigens on paraffin-embedded sections of 47 cases. Hans, Choi and Tally subtypes were classified, and univariate and multivariate analyses were used to elucidate the relationship between the subtypes and prognosis. RESULTS: In the 47 cases, the expression of Bcl-2 in the tumor cells was 46.8%, CD10 4.3%, Bcl-6 70.2%, Mum-1 53.2%, GCET-1 36.2%, BLIMP-1 4.3%, FOXP-1 63.8% and LMO-2 19.2%. The positive rate of Ki-67 was 30% to 95%, with a median of 80%, of which 12 cases (25.5%) was > or = 90%. The Hans subtype classification showed 16 cases (34.0%) were of GCB type and 31 cases (66.0%) of non-GCB type. The Choi subtype classification showed 16 cases (34.0%) were of GCB type and 31 cases (66.0%) of ABC type. The Tally subtype classification showed 6 cases (12.8%) were of GCB type and 41 cases (87.2%) of non-GCB type. CONCLUSIONS: The results of this study show that there is no significant correlation between the three subtypes and prognosis. The prognosis is correated with post-operative radiotherapy, chemotherapy and MTX therapy. PMID- 22780929 TI - [Cytogenetic profiles of follicular lymphoma]. AB - OBJECTIVE: To study the cytogenetic profiles of follicular lymphoma (FL) in Chinese patients. METHODS: Conventional karyotype in 57 FL patients from Shanghai area was analyzed. Fluorescence in-situ hybridization (FISH) for t(14;18) and Bcl 6 and IgH gene rearrangement was performed in these cases. RESULTS: The most frequent breakpoints (frequency > or = 10% ) of the 57 FL cases were at band 14q32 (68.4%), 18q21 (38.6%), 3q27 (21.1%), 1q10 (15.8%) and 1q21 (12.3%). Nineteen (33.3%) of the 57 cases had t(14;18). The breakpoint of 18q21 and t(14;18) were more frequent in FL grade 1-2 and less frequent in FL grade 3 (57.6% vs. 12.5%; 54.5% vs. 4.2%, P < 0.05), whereas the 3q27/Bcl-6 rearrangement was more frequent in FL grade 3 and less frequent in FL grade 1-2 (37.5% vs. 9.1% , P < 0.05). The cohort of FL was more frequent in gains of chromosomes X, 1q, 5, 6p, 7 and 12q and losses of chromosomes 1p, 6p and 14q32. Gain of 18q was more frequent in FL grade 1-2 than in FL grade 3 (P < 0.05). Loss of 14q32 was more frequent in t(14;18) negative FL than in t(14;18) positive FL (P < 0.05). CONCLUSIONS: Compared with the data of Western patients reported in the literature, Chinese FL cases had distinct cytogenetic profiles from Western FL cases that the t(14;18) is less frequent and the gain of 1q is more frequent in Chinese FL cases, which are more significant in high grade FL. PMID- 22780930 TI - [Comparison of three methods to delineate internal gross target volume of the primary hepatocarcinoma based on four-dimensional CT simulation images]. AB - OBJECTIVE: To compare the position and magnitude of internal target gross volume (IGTV) of primary hepatocarcinoma delineated by three methods based on four dimensional computed tomography (4D-CT) and to investigate the relevant factors affecting the position and magnitude. METHODS: Twenty patients with primary hepatocarcinoma after transcatheter arterial chemoembolization (TACE) underwent big bore 4D-CT simulation scan of the thorax and abdomen using a real-time position management (RPM) system for simultaneous record of the respiratory signals. The CT images with respiratory signal data were reconstructed and sorted into 10 phase groups in a respiratory cycle, with 0% phase corresponding to end inhale and 50% corresponding to end-exhale. The maximum intensity projection (MIP) image was generated. IGTVs of the tumor were delineated using the following three methods: (1) The gross tumor volume (GTV) on each of the ten respiratory phases of the 4D-CT image set was delineated and fused ten GTV to produce IGTV10; (2) The GTVs delineated separately based on 0% and 50% phase were fused to produce IGTV(IN+EX); (3) The visible tumor on the MIP image was delineated to produce IGTV(MIP). Twenty patients were divided into groups A and B based on the location of the target center,and were divided into groups C and D based on the tumor maximum diameter. The patients were divided into groups E and F based on the three-dimensional (3D) motion vector of the target center. The position of the target center, the volume of target, the degree of inclusion (DI) and the matching index (MI) were compared reciprocally between IGTV10, IGTV(IN+EX) and IGTV(MIP), and the influence of the tumor position and 3D motion vector on the related parameters were compared based on the grouping. RESULTS: The average differences between the position of the center of IGTVs on direction of X, Y and Z axes were less than 1.5 mm, and the difference was statistically not significant. The volume of IGTV10 was larger than that of IGTV(IN+EX), but the difference was not significant (t = 0.354, P = 0.725). The volume of IGTV10 was larger than that of IGTV(MIP) but the difference was not significant (t = -0.392, P = 0.697). The ratio of IGTV(IN+EX) to IGTV10 was 0.75 +/- 0.15 and the ratio of IGTV(MIP) to IGTV10 was 0.78 +/- 0.14. The DI of IGTV(IN+EX) in IGTV10 was (74.85 +/- 15.09)% and that of IGTV(MIP) in IGTV10 was (68.87 +/- 13.69)%. The MI between IGTV10 and IGTV(IN+EX), IGTV10 and IGTV(MIP) were 0.75 +/- 0.15 and 0.67 +/- 0.13, respectively. The median of ratio of IGTV(IN+EX)/ IGTV10 was 0.57 in group A versus 0.87 in group B, statistically with a significant difference between the groups A and B (Z = -3.300,P = 0.001). The median of ratio of IGTV(MIP)/IGTV10 was 0.51 in the group A and 0.72 in group B, with a significant difference between the groups A and B (Z = -3.413, P = 0.001). The median of ratio of IGTV(IN+EX)/IGTV10 was 0.79 in group C versus 0.74 in group D, with a difference not significant (Z = -0.920, P = 0.358). The median of ratio of IGTV(MIP)/IGTV10 was 0.85 in group C versus 0.80 in group D, with a non significant difference (Z = -0.568, P = 0.570). The median of ratio of IGTV(IN+EX)/IGTV10 was 0.87 in group E versus 0.68 in group F, with a significant difference between the two groups (Z = -2.897, P = 0.004). The median of ratio of IGTV(MIP)/IGTV10 was 0.85 in the group E versus 0.81 in the group F, with a non significant difference (Z = -0.568, P = 0.570). CONCLUSIONS: The center displacement of the IGTVs delineated separately by the three techniques based on 4D-CT images is not obvious. IGTV(IN+EX) and IGTV(MIP) can not replace IGTV10, however, IGTV(IN+EX) is more close to IGTV10 comparing with IGTV(MIP). The ratio of IGTV10 and IGTV(MIP) is correlated to the 3D motion vector of the tumor. When the tumor is situated in the upper part of the liver and with a 3D motion vector less than 9 mm, IGTV10 should be the best IGTV. PMID- 22780931 TI - [Association of serum lipid profile with distant metastasis in breast cancer patients]. AB - OBJECTIVE: In order to investigate whether the presence of distant metastases is associated with serum lipid abnormalities. METHODS: The fasting serum lipid profile and various clinicopathological data of 324 breast cancer patients with and without synchronous distant metastases were collected and analyzed. The serum lipid profile, including total cholesterol (TC), triglycerides (TG), low-density (LDL-C) and high-density lipoprotein cholesterol (HDL-C) was determined. The nutritional status, the serum albumin was measured and body mass index (BMI) was calculated. Univariate analysis and multiple logistic regression analysis were carried out to investigate the association of serum lipid profile with distant metastases. RESULTS: Univariate analysis showed that the distant metastasis rate was significantly higher in the breast cancer patients with an higher level of serum TC, TG, LDL-C, and LDL-C/HDL-C ratio (P < 0.05). Multiple logistic regression analysis showed that higher serum levels of TC, LDL-C and LDL-C/HDL-C ratio were independent risk factors for distant metastasis in breast cancer (OR = 2.324, 2.648 and 4.862, respectively). CONCLUSIONS: Hyperlipidemia is significantly associated with the distant metastasis in breast cancer patients. Monitoring of serum lipid profile may be helpful to predict the occurrence of distant metastasis in breast cancer patients. PMID- 22780932 TI - [Expression of HMGB1 protein in laryngeal squamous cell carcinoma and its clinical significance]. AB - OBJECTIVE: To evaluate the expression of HMGB1 protein in tissue specimens of laryngeal squamous cell carcinoma (LSCC) and adjacent normal mucosa, and explore the correlation of HMGB1 protein expression with clinicopathologic features and prognosis in LSCC. METHODS: Ninty-three cases of LSCC and 5 cases of adjcent mucosal tissue samples were included in this study. Immunohistochemical staining was performed on paraffin-embedded tissue specimens to examine the HMGB1 protein expression. The data were futher correlated with the clinicopathological features and prognosis of the LSCC patients. RESULTS: The positive rates of HMGB1 expression in LSCC specimens was 87.1%, significantly higher than that in the adjcent normal mucosa samples (46.7%, P = 0.001), and its overexpresion was closely correlated with T stage (Chi2 = 10.878, P = 0.004), clinical stage (Chi2 = 21.115, P < 0.01), metastasis (Chi2 = 28.298, P < 0.01) and recurrence (Chi2 = 14. 923, P = 0.001) in patients with LSCC. Patients with HMGB1 overexpression had both poorer disease-free survival and poorer overall survival compared with that in patients with low HMGB1 expression (Chi2 = 13.815, Chi2 = 11.912; Both P < 0.01). Univariate and multivariate Cox regression analyses revealed that HMGBI expression is an independent prognostic factor for patients with LSCC. CONCLUSIONS: The results of this study demonstrate that HMGB1 protein expression is significantly increased in LSCC tissues, and HMGB1 protein overexpression is associated with a poorer prognosis in patients with LSCC. These results suggest that HMGB1 may play a critical role in the initiation and progression of LSCC, implicating HMGB1 may become a valuable marker for the prediction of prognosis in patients with LSCC. PMID- 22780933 TI - [Clinical characterization of 61 cases of diffuse large B-cell lymphoma with different prognosis]. PMID- 22780934 TI - [Clinical features and prognosis of children with lymphoblastic lymphoma]. AB - OBJECTIVE: To evaluate the clinical characteristics of childhood lymphoblastic lymphoma (LBL) and therapeutic efficacy of BCH-LBL-2003 regimen modified from BFM 90 protocol. The drug-related toxicities and prognostic factors were explored at the same time. METHODS: From Janurary 2003 to December 2009, 112 newly diagnosed LBL patients at the Hematology Center of Beijing Children's Hospital were enrolled in this study. The patients were treated with modified BFM-90-LBL protocol. RESULTS: At a median follow-up of 29 months (1 to 90 months), the patients were evaluated on day 33 and at the end of induction therapy. The bone marrow complete remission (CR) rates were 96.4% and 100%, respectively. Meanwhile, the complete remission (CR) rates of tumor were 77.7% and 94.5%, and the partial remission (PR) rates were 22.3% and 5.5%, respectively. The overall response rate was 100%. The 3-year overall survival (OS) rate was 89.1% and 5 year OS was 87.0%. The 3-year event-free survival (EFS) was 85.4% and 5-year EFS was 83.3%. Eleven cases relapsed during the treatment (4 BM relapses, 3 CNS recurrences, 3 primary site and 1 lymph node of neck and BM). Eleven patients died (3 died of infection and 8 died of progressive disease after relapse). All patients experienced grade 3-4 hematological toxicity. Univariate analysis indicated that lack of CR at the end of induction therapy, immunophenotype, bulky tumor and course of disease had prognostic significance. CONCLUSIONS: Lymphoblastic lymphoma in childhood and adolescence is highly aggressive. BCH-LBL 2003 protocol is very effective. The treatment-associated side effects were tolerable. Patients who didn't get CR at the end of induction therapy, with T cell immunophenotype, with bulky disease and the course of disease less than 30 days may have a poor prognosis. PMID- 22780935 TI - [Efficacy analysis of THP-containing regimens as neoadjuvant and adjuvant chemotherapy for primary breast cancer]. AB - OBJECTIVE: To evaluate the effect of anthracycline pirarubicin-based regimen in association with different ways of fluorouracil (5-Fu) as neoadjuvant and adjuvant chemotherapy for primary breast cancer. METHODS: Two hundred and eighty nine primary breast cancer patients who were to be operated, two to eight cycles of pirarubicin in association with cyclophosphamide and 5-Fu (CTF or CTFci regimen) were given before operation. The pathological response rate, effect and its relation with the infusion routes of 5-Fu were analyzed. RESULTS: The overall pathological complete remission (pCR) rate was 28.4%. The median follow-up period was 39 months. The 5-year DFS was 87.6% (95% CI:82.1% to 92.7%), 5-year DDFS was 89.9% (95% CI:84.0% to 95.8%), and overall survival was 99.6%. CTFci (5-Fu, continuous infusion) regimen was superior to CTF regimen in pCR rates (32.3% vs. 20.2%, P = 0.037), and 5-year DDFS were 92.9% and 80.1%, respectively (P = 0.015). The pCR group was superior to non-pCR group in 5-year DDFS (92.4% vs. 85.6%, P = 0. 033). The pCR rate of patients with ER/PR-positive tumor was significantly lower than those of ER/PR-negative (P = 0.004). The 5-year DDFS rates of HER-2 (+) and HER-2(-) groups were 75.0% and 91.9%, respectively (P = 0.043). In the ER/PR-positve group, the 5-year DDFS of CTFci regimen was superior to those of CTF regimen, 91.4% vs. 81.4% (P = 0.047). CONCLUSIONS: CTF/CTFci regimen as neoadjuvant and adjuvant chemotherapy is effective for primary breast cancer. CTFci regimen is superior to CTF regimen in pathological complete response rate and 5-year DDFS. CTFci regimen may do better to ER/PR (+) patients' benefits compared with CTF regimen. PMID- 22780936 TI - [Comparison of the efficacy of second line EGFR TKIs followed by third line pemetrexed or the reverse sequence in the treatment of advanced lung adenocarcinoma]. AB - OBJECTIVE: To compare the efficacy of second-line EGFR-TKIs followed by third line pemetrexed with second-line pemetrexed followed by third-line EGFR-TKIs in patients with advanced lung adenocarcinoma. METHODS: From March 2007 to August 2008, 83 patients with advanced lung adenocarcinoma who failed standard first line chemotherapy were included in this study. The patients who received EGFR TKIs as second-line therapy followed by third-line pemetrexed were designated as group A (n = 45). The patients who received pemetrexed as second-line therapy followed by third-line EGFR-TKIs were designated as group B (n = 38). PFS and MST were estimated with Kaplan-Meier analysis and the difference between groups were compared with Log-rank test. RESULTS: The progression-free survival (PFS) after second-line therapy in the groups A and B was 8.05 months (95% CI, 5.90 to 10.20) and 4.20 months (95% CI, 3.33 to 5.06), respectively (P = 0.001). The PFS after second-line therapy in smokers and non-smokers was 3.69 months (95% CI, 5.00 to 7.59) and 7.12 months (95% CI, 5.51 to 8.38), respectively (P = 0.007). The PFS of male and female patients was 5.56 months (95% CI, 4.02 to 7.10) and 6.85 months (95% CI, 4.98 to 7.58), respectively (P = 0.279). The PFS after third-line therapy in groups A and B was 6.88 months (95% CI, 5.07 to 8.69) and 7.60 months (95% CI, 5.59 to 9.12) respectively, (P = 0.899). The PFS after third-line therapy in smokers and non-smokers was 4.95 months (95% CI, 2.83 to 7.05) and 8.49 months (95% CI, 6.27 to 10.76), respectively (P = 0.050). The PFS after third-line therapy in male and female patients was 5. 96 months (95% CI, 4.02 to 7.91) amd 8.38 months (95% CI, 5.68 to 11.07), respectively (P = 0.176). The MST in groups A and B was 23.60 months (95% CI, 19.23 to 28.00) and 15.58 months (95% CI, 11.85 to 19.32), respectively (P = 0.021). The MST in smokers and non-smokers was 11.99 months (95% CI, 8.55 to 15.49) and 23.18 months (95% CI, 19.33 to 27.02), respectively (P = 0.001). The MST in male and female patients was 17.40 months (95% CI, 13. 19 to 21.61) and 22.74 months (95% CI, 18.29 to 27.19), respectively (P = 0.111). CONCLUSIONS: Second line EGFR TKIs followed by third line pemetrexed regimen improves the PFS and MST compared with the regimen second line pemetrexed followed by third line EGFR TKIs in patients with advanced lung adenocarcinoma. Smoking status is an independent prognostic factor. Survival is not influenced by gender. Prospective clinical trials are needed to confirm these findings. PMID- 22780937 TI - [Efficacy and adverse effets of nimotuzumab plus palitaxel liposome and carboplatin in the treatment for advanced non-small cell lung cancer]. AB - OBJECTIVE: To evaluate the efficacy of nimotuzumab combined with palitaxel liposome and carboplatin (LP) regimen for treatment of advanced non-small cell lung cancer (NSCLC), and to observe the changes of tumor markers and toxicities in the treatment. METHODS Forty-one patients with advanced NSCLC were randomly divided into 2 groups: 21 patients in the observation group were treated with nimotuzumab (200 mg per week for 6 weeks), palitaxel liposome 160 mg/m2 and carboplatin (AUC = 6). 20 patients in the control group were given LP regimen. Each group completed two cycles of chemotherapy. The level of tumor markers (CEA, CYFR21-1 and NSE) and toxicities were checked at one week before and after the treatment. Thoracic CT examinations were taken before treatment and at the fourth week and eighth week after treatment. RESULTS: In the observation group, there were 2 cases of CR, 7 cases of PR, 9 cases of SD and 3 cases of PD. The objective response rate (RR) was 42. 9% in the observation group. In the control group, there were 1 case of CR, 6 cases of PR, 8 cases of SD and 5 cases of PD, with a RR of 35.0% in this group. There was no significant difference in the RR between the two groups (P = 0.751). The time to progression (TIP) was 6. 9 months in the observation group and 5. 7 months in the control group, with a significant difference (P = 0.027). The levels of NSE decreased significantly in both groups and showed a significant difference (P = 0.039). The levels of CEA and CYFRA21 in both groups were decreased after treatment, but did not show a significant difference before and after treatment, respectively. Except 3 cases had I-II skin toxicities on the faces in the observation group, there was no significant difference in toxicities between the two groups. CONCLUSION: Nimotuzmab combined with LP regimen shows a synergistic effect, can increase the efficacy and prolong TFP in advanced NSCLC patients. The toxicities are mild and tolerable. PMID- 22780938 TI - [Treatment outcome of allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies not in remission]. PMID- 22780939 TI - [More attention should be paid to the understanding of gastroenteropancreatic neuroendocrine tumors]. PMID- 22780941 TI - Reasons for blood donation deferral in sub-Saharan Africa: experience in Ivory Coast. AB - INTRODUCTION: Blood donor selection is important to ensure the safety of both donors and recipients. There is a paucity of data on reasons for blood donor deferral in Ivory Coast. The aim of this study was to identify the reasons for predonation deferral at a blood collection site at General Hospital, Yopougon Attie in Abidjan. MATERIALS AND METHODS: The investigators conducted a retrospective audit of data pertaining to donor deferral for blood donors that presented to the general hospital of Yopugon Attie from January 1, 2006 to December 31, 2008. RESULTS: A total of 10,694 prospective blood donors, presented over the study period, and 24,363 attempts to donate were registered. The majority were repeat blood donors (77.4%). A total of 2618 (10.8%) donors were deferred. The most frequent reason for deferral was a low hemoglobin level (42.5%), with females constituting the majority of those deferred. The second most frequent reason for deferral was a reported change of or new sexual partner (34.3%); male donors were predominant in this group. Additional reasons for deferral included short interdonation interval (4.6%) and reactivity for a screened biomarker (2.3%). CONCLUSION: Although the rates for permanent and temporary deferral rates are similar between the Ivory Coast and high-middle income countries, the causes and demographics differ. The reasons for exclusion are preventable through awareness and education of prospective blood donors. PMID- 22780942 TI - Validation and implementation of a new hemoglobinometer for donor screening at Canadian Blood Services. AB - BACKGROUND: Hemoglobin (Hgb) determination is an essential part of donor qualification. We assessed and implemented a new spectrophotometer for donor Hgb determination. STUDY DESIGN AND METHODS: Precision, accuracy, and ease of use were assessed on a prototype DiaSpect analyzer (DiaSpect Medical, GmBH, Sailauf, Germany). A protocol to qualify the analyzer was developed and executed preimplementation. Samples were developed for periodic quality control (QC). Postimplementation performance was assessed based on QC results and trending of deferral rates. RESULTS: Precision was excellent, with a coefficient of variation of 0.53%-1.14% per sample. The correlation coefficient between capillary DiaSpect and venous laboratory autoanalyzer measurements was 0.736. After 169 out of 223 analyzers failed to qualify on our initial protocol, all were successfully qualified with the use of a modified protocol, adjusted to avoid sources of variability. Because commercial controls proved inadequate, in-house samples were developed for periodic QC. Postimplementation, all analyzers had adequate QC results. Deferral rates decreased from 10.1 to 8.1% (p < 0.0001) for female donors and from 0.8 to 0.6% for male donors (p < 0.0001). The system was faster and easier to use compared with our previous two-step process. CONCLUSION: We successfully implemented a new spectrophotometer, which resulted in greater efficiency, improved ease of use, and decreased deferrals. PMID- 22780943 TI - Health care utilization of patients diagnosed with idiopathic thrombotic thrombocytopenic purpura in a commercially insured population in the United States. AB - BACKGROUND: Incident idiopathic thrombotic thrombocytopenic purpura (TTP) is an uncommon, potentially fatal blood disorder for which there are little or no data on health care costs. STUDY DESIGN AND METHODS: Patients satisfying a validated claims-based algorithm including an inpatient diagnosis of TTP and plasma exchange (PE) procedure during the period January 1, 2001 to May 31, 2008 were identified in the HealthCore Integrated Research Database. To characterize patterns of treatment and payments, a quantitative evaluation of comorbidities and treatments, health care utilization, and payments among this population of patients was conducted. All patients were followed until death, end of health plan enrollment, or 365 days after the TTP hospitalization, whichever occurred first. RESULTS: One hundred fifty-one patients met the claims coding algorithm. Mean total health care payments for the TTP hospitalization were $56,347 (standard deviation [SD] $80,230). Ten patients (6.6%) died during the hospitalization for TTP. Mean payments for PE services in the month following discharge were $9127 (SD $20,840). Several patients required prolonged PE during the acute TTP phase (up to 116 separate exchanges over a period of 365 days), prolonging required treatment and skewing payments and resource utilization during the 365-day period following discharge from the index TTP hospitalization. CONCLUSION: These data document the health care resource utilization by patients with idiopathic TTP, demonstrating that management of these patients is not only expensive but also skewed, with some patients requiring prolonged treatment. These data can contribute to cost-effectiveness models when new treatments for TTP become available. PMID- 22780944 TI - Events at blood collection area due to nonconforming blood bags and plateletpheresis kits: need for timely corrective and preventive actions. AB - BACKGROUND: Good blood banking practice requires that every effort should be made to detect any deviation or defect in blood bank products and to identify any potential risk to blood donor or recipient(s). We report the findings of an exercise that provide an insight into why feedback from the user side is crucial. STUDY DESIGN AND METHODS: Various events involving blood bags and plateletpheresis kits and the corresponding appropriate actions instituted for remedial measures were recorded. These scattered events were recorded for 6 months following the use of a new batch of improved blood bags with add-on features. Several events related to plateletpheresis kits from three different manufacturers were also recorded for 1 year. RESULTS: The affected blood bags were utilized with no untoward incident. The complaint was closed following satisfactory response from the blood bag manufacturing company that acted in a timely manner in addressing the root causes of the problems. However, corrective and preventive actions (CAPA) could not be implemented for plateletpheresis kits. The rate of undesirable events was higher with plateletpheresis kits as compared with whole blood bags (1.75% vs. 0.06%). CONCLUSION: As defects or deviations that trigger the need for CAPA can stem from numerous sources, it is important to clearly identify and document the problems and level of risk so that appropriate investigations can be instituted and remedial actions can be taken in a timely manner. This study demonstrates the usefulness of a quality initiative to collate and analyze blood product faults in conjunction with blood product manufacturers. PMID- 22780945 TI - Improving blood transfusion practice by regular education in the United Arab Emirates. AB - BACKGROUND: A cross-match to transfused unit ratio of less than 2.0 is frequently used to assess performance in many hospital blood banks. This brief report was initiated to evaluate the practice at a local hospital and to emphasize the importance of regular educational sessions to improve blood transfusion practice. METHOD: Retrospective data on cross-match : transfused (C : T) ratio of all departments was collected and educational sessions were given to improve practice. Thereafter, a new set of data was collected and change in practice was assessed. RESULTS: Initial data showed total (C : T) ratio of 1.95. After medical staff education, analysis showed clinically significant improvement in blood utilization practice with a (C : T) ratio of 1.60. CONCLUSION: This brief report indicates the importance of regular physician education, the potential role of blood transfusion committee, and the need to implement clear guidelines for blood transfusion. PMID- 22780946 TI - Letter to the editor. Transfusion safety: is this the business of blood centers? PMID- 22780947 TI - Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates. AB - OBJECTIVES: Xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain tissue. The objective of the study was to evaluate the relationship between retinal and brain levels of these xanthophylls in non-human primates. METHODS: Study animals included rhesus monkeys reared on diets devoid of xanthophylls that were subsequently fed pure lutein or pure zeaxanthin (both at 3.9 umol/kg per day, n = 6/group) and normal rhesus monkeys fed a stock diet (0.26 umol/kg per day lutein and 0.24 umol/kg per day zeaxanthin, n = 5). Retina (4 mm macular punch, 4-8 mm annulus, and periphery) and brain tissue (cerebellum, frontal cortex, occipital cortex, and pons) from the same animals were analyzed by reverse-phase high performance liquid chromatography. RESULTS: Lutein in the macula and annulus was significantly related to lutein levels in the cerebellum, occipital cortex, and pons, both in bivariate analysis and after adjusting for age, sex and n-3 fatty acid status. In the frontal cortex the relationship was marginally significant. Macular zeaxanthin was significantly related to zeaxanthin in the cerebellum and frontal cortex, while the relationship was marginally significant in the occipital cortex and pons in a bivariate model. DISCUSSION: An integrated measure of total macular pigment optical density, which can be measured non-invasively, has the potential to be used as a biomarker to assess brain lutein and zeaxanthin status. PMID- 22780948 TI - Environmental factors influencing older adults' walking for transportation: a study using walk-along interviews. AB - BACKGROUND: Current knowledge on the relationship between the physical environment and walking for transportation among older adults (>= 65 years) is limited. Qualitative research can provide valuable information and inform further research. However, qualitative studies are scarce and fail to include neighborhood outings necessary to study participants' experiences and perceptions while interacting with and interpreting the local social and physical environment. The current study sought to uncover the perceived environmental influences on Flemish older adults' walking for transportation. To get detailed and context-sensitive environmental information, it used walk-along interviews. METHODS: Purposeful convenience sampling was used to recruit 57 older adults residing in urban or semi-urban areas. Walk-along interviews to and from a destination (e.g. a shop) located within a 15 minutes' walk from the participants' home were conducted. Content analysis was performed using NVivo 9 software (QSR International). An inductive approach was used to derive categories and subcategories from the data. RESULTS: Data were categorized in the following categories and subcategories: access to facilities (shops & services, public transit, connectivity), walking facilities (sidewalk quality, crossings, legibility, benches), traffic safety (busy traffic, behavior of other road users), familiarity, safety from crime (physical factors, other persons), social contacts, aesthetics (buildings, natural elements, noise & smell, openness, decay) and weather. CONCLUSIONS: The findings indicate that to promote walking for transportation a neighborhood should provide good access to shops and services, well-maintained walking facilities, aesthetically appealing places, streets with little traffic and places for social interaction. In addition, the neighborhood environment should evoke feelings of familiarity and safety from crime. Future quantitative studies should investigate if (changes in) these environmental factors relate to (changes in) older adults' walking for transportation. PMID- 22780949 TI - Regulation of SIRT1 determines initial step of endometrial receptivity by controlling E-cadherin expression. AB - Sirtuin 1 (SIRT1), originally found as a class III histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. We examined the role of SIRT1 in the regulation of uterine receptivity using Ishikawa and RL95-2 endometrial carcinoma cell lines. Exogenous expression of SIRT1 significantly enhanced E-cadherin expression, while small interfering RNA mediated depletion of endogenous SIRT1 resulted in a significant reduction of E cadherin expression. A SIRT1 activator resveratrol elevated E-cadherin expression in a dose dependent manner, while SIRT1 repressors nicotinamide and sirtinol exhibited a dose dependent reduction of E-cadherin expression. We also showed that both forced expression of SIRT1 and activation of SIRT1 promote E-cadherin driven reporter gene constructs, and SIRT1 is localized at E-cadherin promoter containing E-box elements in Ishikawa cells. Using an in vitro model of embryo implantation, we demonstrate that exogenous expression of SIRT1 and stimulation of SIRT1 activity resulted in the Ishikawa cell line becoming receptive to JAR cell spheroid attachment. Furthermore, resveratrol enhanced E-cadherin and Glycodelin protein expression at sites of intercellular contact, suggesting an additive role of resveratrol in promoting implantation. The initial step of human reproduction depends on the capacity of an embryo to attach and implant into the endometrial wall, and these results revealed the novel mechanism that activation and increased expression of SIRT1 play an important role in uterine receptivity. PMID- 22780950 TI - Inactivation of tyrosinase photoinduced by pterin. AB - Tyrosinase catalyzes in mammals the first and rate-limiting step in the biosynthesis of the melanin, the main pigment of the skin. Pterins, heterocyclic compounds able to photoinduce oxidation of DNA and its components, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder in which the protection against UV radiation fails due to the lack of melanin. Aqueous solutions of tyrosinase were exposed to UV-A irradiation (350 nm) in the presence of pterin, the parent compound of oxidized pterins, under different experimental conditions. The enzyme activity in the irradiated solutions was determined by spectrophotometry and HPLC. In this work, we present data that demonstrate unequivocally that the enzyme is photoinactivated by pterin. The mechanism of the photosensitized process involves an electron transfer from tyrosinase to the triplet excited state of pterin, formed after UV-A excitation of pterin. The biological implications of the results are discussed. PMID- 22780951 TI - Base excision repair gene polymorphisms are associated with inflammation in patients undergoing chronic hemodialysis. AB - Chronic inflammation may increase the risk of mortality for patients undergoing hemodialysis, while enhanced oxidative stress and DNA oxidative damage are involved in the inflammatory response. The purpose of this study was to examine the associations between inflammation and polymorphisms in the base excision repair (BER) system, which protects against oxidative DNA damage, among hemodialysis patients. Data were analyzed from 167 hemodialysis patients and 66 healthy controls. All subjects were evaluated for the expression of inflammatory cytokines (IL-1beta and IL-6) and genotyped for two BER genes, including hOGG1 c.977C>G, MUTYH c.972G>C and AluYb8MUTYH. The results showed that the hemodialysis patients had significantly higher levels of IL-1beta and IL-6 than the healthy controls. In the healthy controls, no patterns of association were observed between the hOGG1 c.977C>G or MUTYH c.972G>C genotypes and IL-1beta or IL-6 levels; however, patients with the MUTYH c.972G/G genotype presented higher levels of IL-1beta than those with the C/C genotype. The AluYb8MUTYH genotype was strongly associated with increased IL-1beta levels among controls and increased IL-1beta and IL-6 levels among hemodialysis patients. Additionally, the synergetic effect of these variations of the BER genes on the levels of IL-1beta and IL-6 was investigated. The combinations of the AluYb8MUTYH genotype with the hOGG1 c.977 C>G or MUTYH c.972 G>C genotypes were associated with the IL-1beta and IL-6 levels in hemodialysis patients. This is the first report showing an association between BER genetic polymorphisms and the inflammatory state during hemodialysis; this association might be mediated by impaired anti-oxidant defense mechanisms. PMID- 22780952 TI - Enrichment Disequilibrium: a novel approach for measuring the degree of enrichment after gene enrichment test. AB - MOTIVATION: Commonly used gene enrichment analysis methods, such as Hypergeometric distribution, play an important role in the functional analysis of interesting gene lists. But the statistical significance obtained by these methods only represents the probability of error that is involved in accepting enrichment, and is not suitable to evaluate the degree of enrichment. Although there have been some methods to measure the enrichment degrees, such as relative enrichment factor, new methods are still needed to meet the requirements for comparing the degree of enrichment. RESULTS: We developed a novel method, Enrichment Disequilibrium (ED), to measure the degree of enrichment. Enrichment equilibrium means that the interesting gene set and the known functional gene set (such as a KEGG pathway) are independent (i.e. random association). ED is defined as the degree of non-independence. Compared with the relative enrichment factor, ED has a clearer biological meaning, is a standardized indicator, and has a symmetrical interval (range from -1 to +1). It is more suitable to measure the enrichment degree. For an interesting gene set, researchers can obtain some significant functional gene sets by traditional enrichment test. Then using ED, they can compare the degree of enrichment among these significant gene sets, and prioritize them. PMID- 22780953 TI - Down-regulation of GnT-V enhances nasopharyngeal carcinoma cell CNE-2 radiosensitivity in vitro and in vivo. AB - The purpose of this study was to investigate the role of GnT-V on radiosensitivity in human nasopharyngeal carcinoma (NPC) both in vitro and in vivo, and the possible mechanism. The GnT-V stably suppressed cell line CNE-2 GnT V/2224 was constructed from CNE-2 by transfection. The radiosensitivity of the cells was studied by CCK-8 assay, flow-cytometry, caspases-3 activity analysis and tumor xenografts model. The expression of Bcl-2, Bax and Bcl-xl was analyzed with or without radiation. The results showed that down-regulation of GnT-V enhanced CNE-2 radiosensitivity. The underlying mechanisms may be link to the cell cycle G2-M arrest and the reduction of Bcl-2/Bax ratio. The results suggest that GnT-V may be a potential target for predicting NPC response to radiotherapy. PMID- 22780955 TI - Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. AB - Advances in biomedical research have generated an unprecedented number of potential targets for therapeutic intervention to treat disease or delay disease progression. Unfortunately, many of these targets are not druggable as they are intracellular, present in many cell types, poorly soluble or rapidly inactivated. Although synthetic drug vehicles have successfully circumvented many of these problems, natural particulates such as exosomes that intrinsically possess many attributes of a drug delivery vehicle are highly attractive as potentially better alternatives. Of the cell types known to produce exosomes, the readily available proliferative, immunosuppressive and clinically tested human mesenchymal stem cell (MSC) is the most prolific producer. Its exosomes are therapeutic in animal model of disease and exhibit immunosuppressive activity. The quality and quantity of exosome production is not compromised by immortalization to create a permanent MSC cell line. Therefore, MSC is well suited for mass production of exosomes that are ideal for drug delivery. PMID- 22780954 TI - Mitochondrial DNA sequence variation in Finnish patients with matrilineal diabetes mellitus. AB - BACKGROUND: The genetic background of type 2 diabetes is complex involving contribution by both nuclear and mitochondrial genes. There is an excess of maternal inheritance in patients with type 2 diabetes and, furthermore, diabetes is a common symptom in patients with mutations in mitochondrial DNA (mtDNA). Polymorphisms in mtDNA have been reported to act as risk factors in several complex diseases. FINDINGS: We examined the nucleotide variation in complete mtDNA sequences of 64 Finnish patients with matrilineal diabetes. We used conformation sensitive gel electrophoresis and sequencing to detect sequence variation. We analysed the pathogenic potential of nonsynonymous variants detected in the sequences and examined the role of the m.16189 T>C variant. Controls consisted of non-diabetic subjects ascertained in the same population. The frequency of mtDNA haplogroup V was 3-fold higher in patients with diabetes. Patients harboured many nonsynonymous mtDNA substitutions that were predicted to be possibly or probably damaging. Furthermore, a novel m.13762 T>G in MTND5 leading to p.Ser476Ala and several rare mtDNA variants were found. Haplogroup H1b harbouring m.16189 T > C and m.3010 G > A was found to be more frequent in patients with diabetes than in controls. CONCLUSIONS: Mildly deleterious nonsynonymous mtDNA variants and rare population-specific haplotypes constitute genetic risk factors for maternally inherited diabetes. PMID- 22780956 TI - Experimental spinal cord stimulation and neuropathic pain: mechanism of action, technical aspects, and effectiveness. AB - Spinal cord stimulation (SCS) is a valuable treatment for chronic intractable neuropathic pain. Although SCS has gone through a technological revolution over the last four decades, the neurophysiologic and biochemical mechanisms of action have only been partly elucidated. Animal experimental work has provided some evidence for spinal as well as supraspinal mechanisms of neuropathic pain relief of SCS. A SCS computer model of the electrical properties of the human spinal cord revealed many basic neurophysiologic principles that were clinically validated later on. The main question in clinical SCS is how to further improve the effectiveness of SCS as there is still a significant failure rate of 30%. In this context, experimental studies are needed to elucidate which target pain neuron(s) are involved, as well as with what exact electrical stimulation this target neuron can be influenced to produce an optimal supapression of neuropathic pain. This article reviews the basic clinical and experimental technical aspects in relation to the effectiveness of SCS in view of recent understanding of the dorsal horn pain circuit involved. These data may then result in experiments needed for an improved understanding of the mechanisms underlying SCS and consequently lead to improvement and increased effectiveness of SCS in neuropathic pain as a clinical therapy. PMID- 22780957 TI - Determinants of maternal health services utilization in urban settings of the Democratic Republic of Congo--a case study of Lubumbashi City. AB - BACKGROUND: The use of maternal health services, known as an indirect indicator of perinatal death, is still unknown in Lubumbashi. The present study was therefore undertaken in order to determine the factors that influence the use of mother and child healthcare services in Lubumbashi, Democratic Republic of the Congo. METHODS: This was transversal study of women residing in Lubumbashi who had delivered between January and December 2009. In total, 1762 women were sampled from households using indicator cluster surveys in all health zones. Antenatal consultations (ANC), delivery assisted by qualified healthcare personnel (and delivery in a healthcare facility) as well as postnatal consultations (PNC) were dependent variables of study. The factors determining non-use of maternal healthcare services were researched via logistic regression with a 5% materiality threshold. RESULTS: The use of maternal healthcare services was variable; 92.6% of women had attended ANC at least once, 93.8% of women had delivered at a healthcare facility, 97.2% had delivered in the presence of qualified healthcare personnel, while the rate of caesarean section was 4.5%. Only 34.6% postnatal women had attended PNC by 42 days after delivery. During these ANC visits, only 60.6% received at least one dose of vaccine, while 38.1% received Mebendazole, 35.6% iron, 32.7% at least one dose of SulfadoxinePyrimethamine, 29.2% folic acid, 15.5% screening for HIV and 12.8% an insecticide treated net.In comparison to women that had had two or three deliveries before, primiparous and grand multiparous women were twice as likely not to use ANC during their pregnancy. Women who had unplanned pregnancies were also more likely not to use ANC or PNC than those who had planned pregnancies alone or with their partner. The women who had not used ANC were also more likely not to use PNC. The women who had had a trouble-free delivery were more likely not to use PNC than those who had complications when delivering. CONCLUSION: In Lubumbashi, a significant proportion of women continue not to make use of healthcare services during pregnancy, as well as during and after childbirth. Women giving birth for the first time, those who have already given birth many times, and women with an unwanted pregnancy, made less use of ANC. Moreover, women who had not gone for ANC rarely came back for postnatal consultations, even if they had given birth at a healthcare facility. Similarly, those who gave birth without complications, less frequently made use of postnatal consultations. As with ANCs, women with unwanted pregnancies rarely went for postnatal visits.In addition to measures aimed at reinforcing women's autonomy, efforts are also needed to reinforce and improve the information given to women of childbearing age, as well as communication between the healthcare system and the community, and participation from the community, since this will contribute to raising awareness of safe motherhood and the use of such services, including family planning. PMID- 22780958 TI - Portuguese man-of-war (Physalia physalis) envenomation on the Aquitaine Coast of France: an emerging health risk. AB - CONTEXT: The Portuguese man-o-war is a cnidaria classically found in tropical waters. It can cause serious and even life-threatening envenomation in swimmers, surfers and seafarers. Presence of the Atlantic species Physalia physalis has long been reported in European coastal waters but was always an exceptional event. OBJECTIVE: To describe the experience of the Bordeaux Poison centre about Physalia stings since the first collective episode reported in 2008. METHODS: Clinical retrospective description of cases series of Physalia envenomations reported to the local poison centre from 2008 to 2011 inclusive. RESULTS: In the summer of 2008, multiple-case incident involving 40 victims were recorded on the same day on one beach in the Southern French Atlantic coast. The following year in 2009, no envenomation cases were reported in the same area, but in the next 2 years, numerous man-of-war envenomations occurred along the Aquitaine coast, that is, 154 cases in 2010 and 885 in 2011. Portuguese man-o-war stings led to severe manifestations with 15-20% of patients suffering of general symptoms that were sometimes severe enough to be considered as potentially life-threatening (8% of patients in 2011, most frequent signs: muscle pain and cramps with fasciculations, confusion and drowsiness, fainting, respiratory distress). No deaths due to Portuguese man-o-war envenomation were reported over the 4-year study period. CONCLUSION: The results suggest that national multidisciplinary summer surveillance program in the Aquitaine coast is required in order to provide alerts to the public, to better identify patients at risk for developing severe clinical symptoms, and hopefully to improve quality of health care. PMID- 22780959 TI - Coinage metal complexes against breast cancer. AB - Breast cancer is still the leading cause of cancer deaths among women worldwide, and new therapies to treat this dangerous disease are desperately needed. The serendipitously found anticancer drug cisplatin and its second-generation congener carboplatin appear to be promising drug systems for the treatment of breast tumors, in particular of multidrug resistant and highly aggressive triple negative subtypes. In the wake of these platinum drugs, complexes of the coinage metals copper, silver, and gold were developed that showed enhanced selectivity for breast cancer while causing fewer and weaker side-effects. This review takes stock of the latest developments in the field of coinage metal anticancer drugs with an emphasis on their biological and mechanistic aspects. Pertinent literature is covered up to 2012. PMID- 22780960 TI - Subtype-selective dopamine receptor radioligands for PET imaging: current status and recent developments. AB - This review presents a general overview of the subtype-selective dopamine receptor radioligands for in vivo imaging of dopamine receptor expression by positron emission tomography (PET). Besides the (11)C- and (18)F-labeled radioligands which are already in clinical use, a summary of subtype-selective radioligands which had been studied in vitro and in vivo is provided, which shines light onto the current status and recent developments in this field of radiopharmaceutical research. PMID- 22780962 TI - Predictors of placebo response in adults with attention-deficit/hyperactivity disorder: data from 2 randomized trials of osmotic-release oral system methylphenidate. AB - OBJECTIVE: To find potential correlates of placebo response in adults with attention-deficit/hyperactivity disorder (ADHD) and gain insights into why placebo response may be high in clinical trials. METHOD: Post hoc analysis of placebo data from 2 randomized controlled trials of osmotic-release oral system (OROS) methylphenidate in adults with ADHD defined according to the Diagnostic and Statistical Manual of Mental Diseases, Fourth Edition: the Long-Acting Methylphenidate in Adults with ADHD (LAMDA-I) study (2005-2006, 5 weeks, n = 95) and the LAMDA-II study (2008-2009, 13 weeks, n = 97). The primary efficacy measure was the Conners' Adult ADHD Rating Scale-observer rated, short version (CAARS:O-SV). Predictors of CAARS:O-SV change were assessed using a random intercepts model with demographic and disease-related parameters as independent variables. Sensitivity analyses were conducted using the CAARS self-report (CAARS:S-S) and a categorical response criterion (improvement of > 30% in CAARS:O SV), and in subjects who completed the study. RESULTS: In LAMDA-I, mean +/- SD change in CAARS:O-SV was -7.6 +/- 9.9 with placebo and -11.9 +/- 10.6 with OROS methylphenidate. Higher baseline CAARS score (P = .007) and lower educational achievement (P = .014) were significantly associated with greater improvement in placebo-treated subjects. In LAMDA-II, mean +/- SD change in CAARS:O-SV was -10.4 +/- 11.0 and -14.1 +/- 10.7 in subjects receiving placebo and OROS methylphenidate, respectively. Variables significantly associated with greater placebo response were higher baseline CAARS:O-SV (P = .019), shorter time since ADHD diagnosis (P < .045), and younger age (P = .014). None of the sensitivity analyses challenged the outcomes. CONCLUSIONS: Possible predictors of placebo response in adults with ADHD include higher severity of ADHD symptoms, younger age, shorter time since diagnosis, and lower educational level. PMID- 22780961 TI - Predicting new indications for approved drugs using a proteochemometric method. AB - The most effective way to move from target identification to the clinic is to identify already approved drugs with the potential for activating or inhibiting unintended targets (repurposing or repositioning). This is usually achieved by high throughput chemical screening, transcriptome matching, or simple in silico ligand docking. We now describe a novel rapid computational proteochemometric method called "train, match, fit, streamline" (TMFS) to map new drug-target interaction space and predict new uses. The TMFS method combines shape, topology, and chemical signatures, including docking score and functional contact points of the ligand, to predict potential drug-target interactions with remarkable accuracy. Using the TMFS method, we performed extensive molecular fit computations on 3671 FDA approved drugs across 2335 human protein crystal structures. The TMFS method predicts drug-target associations with 91% accuracy for the majority of drugs. Over 58% of the known best ligands for each target were correctly predicted as top ranked, followed by 66%, 76%, 84%, and 91% for agents ranked in the top 10, 20, 30, and 40, respectively, out of all 3671 drugs. Drugs ranked in the top 1-40 that have not been experimentally validated for a particular target now become candidates for repositioning. Furthermore, we used the TMFS method to discover that mebendazole, an antiparasitic with recently discovered and unexpected anticancer properties, has the structural potential to inhibit VEGFR2. We confirmed experimentally that mebendazole inhibits VEGFR2 kinase activity and angiogenesis at doses comparable with its known effects on hookworm. TMFS also predicted, and was confirmed with surface plasmon resonance, that dimethyl celecoxib and the anti-inflammatory agent celecoxib can bind cadherin-11, an adhesion molecule important in rheumatoid arthritis and poor prognosis malignancies for which no targeted therapies exist. We anticipate that expanding our TMFS method to the >27 000 clinically active agents available worldwide across all targets will be most useful in the repositioning of existing drugs for new therapeutic targets. PMID- 22780963 TI - Midgut-enriched receptor protein tyrosine phosphatase PTP52F is required for Drosophila development during larva-pupa transition. AB - To date our understanding of Drosophila receptor protein tyrosine phosphatases (R PTPs) in the regulation of signal transduction is limited. Of the seven R-PTPs identified in flies, six are involved in the axon guidance that occurs during embryogenesis. However, whether and how R-PTPs may control key steps of Drosophila development is not clear. In this study we investigated the potential role of Drosophila R-PTPs in developmental processes outside the neuronal system and beyond the embryogenesis stage. Through systematic data mining of available microarray databases, we found the mRNA level of PTP52F to be highly enriched in the midgut of flies at the larva-pupa transition. This finding was confirmed by gut tissue staining with a specific antibody. The unique spatiotemporal expression of PTP52F suggests that it is possibly involved in regulating metamorphosis during the transformation from larva to pupa. To test this hypothesis, we employed RNA interference to examine the defects of transgenic flies. We found that ablation of endogenous PTP52F led to high lethality characterized by the pharate adult phenotype, occurring due to post pupal eclosion failure. These results show that PTP52F plays an indispensable role during the larva-pupa transition. We also found that PTP52F could be reclassified as a member of the subtype R3 PTPs instead of as an unclassified R-PTP without a human ortholog, as suggested previously. Together, these findings suggest that Drosophila R-PTPs may control metamorphosis and other biological processes beyond our current knowledge. PMID- 22780964 TI - Expression and purification of full length mouse metal response element binding transcription factor-1 using Pichia pastoris. AB - The metal response element binding transcription factor-1 (MTF-1) is an important stress response, heavy metal detoxification, and zinc homeostasis factor in eukaryotic organisms from Drosophila to humans. MTF-1 transcriptional regulation is primarily mediated by elevated levels of labile zinc, which direct MTF-1 to bind the metal response element (MRE). This process involves direct zinc binding to the MTF-1 zinc fingers, and zinc dependent interaction of the MTF-1 acidic region with the p300 coactivator protein. Here, the first recombinant expression system for mutant and wild type (WT) mouse MTF-1 (mMTF-1) suitable for biochemical and biophysical studies in vitro is reported. Using the methyltropic yeast Pichia pastoris, nearly half-milligram recombinant WT and mutant mMTF-1 were produced per liter of P. pastoris cell culture, and purified by a FLAG-tag epitope. Using a first pass ammonium sulfate purification, followed by anti-FLAG affinity resin, mMTF-1 was purified to >95% purity. This recombinant mMTF-1 was then assayed for direct protein-protein interactions with p300 by co immunoprecipitation. Surface plasmon resonance studies on mMTF-1 provided the first quantitative DNA binding affinity measurements to the MRE promotor element (K(d)=5+/-3 nM). Both assays demonstrated the functional activity of the recombinant mMTF-1, while elucidating the molecular basis for mMTF-1-p300 functional synergy, and provided new insights into the mMTF-1 domain specific roles in DNA binding. Overall, this production system provides accessibility for the first time to a multitude of in vitro studies using recombinant mutant and WT mMTF-1, which greatly facilitates new approaches to understanding the complex and varied functions of this protein. PMID- 22780965 TI - ngLOC: software and web server for predicting protein subcellular localization in prokaryotes and eukaryotes. AB - BACKGROUND: Understanding protein subcellular localization is a necessary component toward understanding the overall function of a protein. Numerous computational methods have been published over the past decade, with varying degrees of success. Despite the large number of published methods in this area, only a small fraction of them are available for researchers to use in their own studies. Of those that are available, many are limited by predicting only a small number of organelles in the cell. Additionally, the majority of methods predict only a single location for a sequence, even though it is known that a large fraction of the proteins in eukaryotic species shuttle between locations to carry out their function. FINDINGS: We present a software package and a web server for predicting the subcellular localization of protein sequences based on the ngLOC method. ngLOC is an n-gram-based Bayesian classifier that predicts subcellular localization of proteins both in prokaryotes and eukaryotes. The overall prediction accuracy varies from 89.8% to 91.4% across species. This program can predict 11 distinct locations each in plant and animal species. ngLOC also predicts 4 and 5 distinct locations on gram-positive and gram-negative bacterial datasets, respectively. CONCLUSIONS: ngLOC is a generic method that can be trained by data from a variety of species or classes for predicting protein subcellular localization. The standalone software is freely available for academic use under GNU GPL, and the ngLOC web server is also accessible at http://ngloc.unmc.edu. PMID- 22780966 TI - [New concepts in surgical treatment of rectal cancer]. PMID- 22780967 TI - [NF-kappaB subunits regulate maspin expression in prostate cancer cells in vitro]. AB - OBJECTIVE: To explore how NF-kappaB family members regulate maspin expression in prostate cancer cells. METHODS: The expression of NF-kappaB subunits and maspin was detected by Western blot analysis in prostate cancer DU145, PC-3, and LNCaP cell lines. RNA interference was performed to analyze whether RelB- or RelA deletion affectes cell death as well as the expression of NF-kappaB subunits and maspin. The impact of RelB-silencing in DU145 cells was investigated by flow cytometry. The regulation of RelB on maspin expression in the prostate cancer PC 3 cells was also examined via stable transfection of RelB expression plasmid. RESULTS: RelA, p50, RelB, and p52 were constitutively expressed in androgen independent prostate cancer DU145 and PC-3 cells, while RelB had the highest expression in DU145 cells. Low expression of maspin was detected in LNCaP and DU145 cells, but elevated expression in PC-3 cells. RelB-silencing in DU145 cells by siRNA interference upregulated the endogenous expression of maspin and induced cell apoptosis (13.3+/-4.2)%. Overexpression of RelB in PC-3 cells inhibited the endogenous expression of maspin. RelA-silecing had no significant influence on the endogenous expression of maspin. CONCLUSIONS: The classical and alternative NF-kappaB activitions are sustained in androgen-independent prostate cancer cell lines. The expressions of RelB and maspin are inversely correlated in these cancer cells. The expression of RelB negatively regulates the endogenous expression of maspin, then interferes the cell survival. RelA is not involved in the regulation of maspin expression. PMID- 22780968 TI - [Down-regulation of transcription factor PU.1 via abnormal epigenetic modification in chronic myeloid leukemia]. AB - OBJECTIVE: To investigate the underlying mechanism and clinical significance of PU.1 down-expression in chronic myeloid leukemia (CML) patients. METHODS: Different methylation status of PU.1 promoter region containing 20 CpG islands in normal individuals, CML chronic phase and blast crisis patients, complete cytogenetic remission patients after imatinib treatment, and blast crisis bone marrow K562 CML cells was detected by bisulfite sequencing. Semi-quantitative PCR was used to detect the PU.1 mRNA expression in normal controls, CML chronic phase and blast crisis patients, and blast crisis bone marrow K562 CML cells. Indirect immune fluorescence and Western blot were used to analyze the exprtession of PU.1 protein in normal individuals, CML chronic phase and blast crisis patients, and blast crisis bone marrow K562 CML cells. RESULTS: Aberrant methylation in the promoter region of transcription factor PU.1 was found in both CML chronic phase and blast crisis phase bone marrow cells, as well as in CML blast K562 cells. Down-expression of PU.1 mRNA and protein levels was found in above cells. No methylation in the promoter region of PU.1 was observed in normal individuals, and the PU.1 mRNA and protein expressions were not reduced at all. Furthermore, high methylation status of bone marrow cells was even observed in the CML patients who acquired complete cytogenetic remission. CONCLUSIONS: The results of our study indicate that the epigenetic modification of PU.1 in CML patients and K562 cell line might be responsible for the down-expression of PU.1. The data suggest that aberrant methylation of PU.1 plays a role in CML pathogenesis, therefore, it might serve as a useful biomarker and potential target in therapy for chronic myeloid leukemia. PMID- 22780969 TI - [Expression of a novel biomarker, MR-1S, in ovarian carcinoma and its biological significance]. AB - OBJECTIVE: To investigate the expression of a novel biomarker, human short-type myofibrillogenesis regulator-1 (MR-1S), in ovarian carcinoma and explore its biological significance. METHODS: The MR-1S mRNA levels were analyzed by reverse transcription polymerase chain reaction (RT-PCR) in 23 specimens of ovarian cancers and 20 specimens of control ovarian tissues. The expression of MR-1S in these specimens was detected by real-time PCR and immunohistochemical analysis. In addition, the expression of MR-1S in ovarian cancer SKOV3 cells was determined by immunocytochemisty. MR-1S mRNA and protein level of SKOV3 cells was compared in the two groups treated by carboplatin and paclitaxel at 24 h, 48 h and 72 h, respectively. Furthermore, the expression of MR-1S was analyzed in liner concentration range of the anti-cancer drug, and the potential relation between MR-1S expression and cell apoptosis rate was predicted. RESULTS: The level of MR 1S mRNA was significantly higher in ovarian cancer tissues than those of control tissues by RT-PCR and Real-time PCR analysis. MR-1S protein was overexpressed in ovarian cancer tissues with a positive rate of 78.3% (18/23) than that in the control tissues (30.0%, P<0.05) through IHC analysis. The expression of MR-1S was markedly decreased by treatment with carboplatin and paclitaxel, and there was a direct correlation between MR-1S expression and apoptosis rate, especially in a liner concentration range of paclitaxel at 48 h. CONCLUSION: MR-1S is highly expressed in ovarian cancer cells and tissues, and it may be a promising biomarker for diagnosis and a new target for ovarian cancer therapy. PMID- 22780970 TI - [Expression of Bcl-w protein in human small intestinal adenocarcinoma and effect of Bcl-w siRNA on apoptosis in intestinal adenocarcinoma HuTu-80 cells]. AB - OBJECTIVE: To investigate the expression of apoptosis-related protein Bcl-w in adenocarcinoma of the small intestine, and the apoptotic effect of Bcl-w siRNA on small intestinal adenocarcinoma cells HuTu-80. METHODS: Forty-two tissue samples were examined in our study, including 7 cases from human small intestinal adenocarcinoma, and 35 cases from normal small intestine served as control. The expression of Bcl-w was detected by immunohistochemistry (IHC). Western blot analysis was performed to confirm whether Bcl-w siRNA could effectively down regulate Bcl-w protein after HuTu-80 cells were transfected with Bcl-w siRNA. The cells were treated with chemotherapeutic agent 5-Fu to observe whether Bcl-w protein-silecing affects the pro-apoptotic effect of 5-Fu. Flow cytometry analysis was used for assessment of apoptotic rate of HuTu-80 cells cultured with Bcl-w siRNA alone, with 5-Fu alone, and with combination of Bcl-w siRNA and 5-Fu, using untreated HuTu-80 cells as control. RESULTS: The positive rate of Bcl-w expression was significantly higher in small intestinal adenocarcinoma than that in normal tissue (85.7% vs. 25.7%, P=0.005). Compared with the control group, Bcl w siRNA transfection effectively down-regulated the expression of Bcl-w protein (P<0.05). The apoptosis in HuTu-80 cells was not increased significantly in Bcl-w /-cells compared with that of control group (12.4+/-2.2)% vs. (8.6+/-1.7)% (P>0.05). However, compared with the 5-Fu group, the apoptosis in HuTu-80 cells was effectively enhanced after combination treatment with Bcl-w siRNA and 5-Fu (45.7+/-2.1)% vs. (71.6+/-3.2)% (P<0.05). CONCLUSIONS: Bcl-w protein plays a significant role in the carcinogenesis of human small intestinal adenocarcinoma. Down-regulation of Bcl-w protein in small intestine adenocarcinoma HuTu-80 cells leads them susceptible to 5-Fu. PMID- 22780971 TI - [Generation of a herpes simplex virus-permissive mouse melanoma cell line B16RHSV]. AB - OBJECTIVE: To generate an oncolytic herpes simplex virus (oHSV) permissive mouse melanoma cell line B16RHSV, preserving the tumorigenic ability in syngeneic mice. METHODS: The herpes simplex virus entry mediator (HVEM) gene was amplified by PCR from human melanoma cell line A375, and cloned into pGEM-T Easy vector for sequencing. The HVEM gene was then cloned into pcDNA3 vector to generate pcDNA3 HVEM for transfection of mouse melanoma cell line B16-F10 cells. After that, the putative transfected cells were selected in full growth medium containing G418. The HVEM-expressing cells were isolated by immunomagnetic bead separation. The mouse melanoma cell line expressing oHSV receptor-HVEM, designated as B16RHSV, was generated. The permissibility of B16RHSV cells to oHSV infection was examined with green fluorescence protein (GFP)-expressing oHSV (oHSVGFP). To investigate the tumorigenic ability of both cells in vivo, 2*10(5) cells in 100 ul were subcutaneously inoculated into the right flanks of C57/BL mice. RESULTS: In vitro, the B16RHSV mouse melanoma cells were shown by fluorescence microscopy capable of being infected by oHSVGFP. In vivo, the B16RHSV cells, like their wild type counterpart, grew to form melanoma in syngeneic mice. CONCLUSION: A herpes simplex virus-permissive mouse melanoma cell line was established. Its tumorigenicity remained unchanged. PMID- 22780972 TI - [ICAM-1 469K/E gene polymorphisms increase the risk of gastric dysplasia]. AB - OBJECTIVE: To investigate the influence of ICAM-1 469K/E gene polymorphisms on the risk of atrophic gastritis and dysplasia. METHODS: The ICAM-1 469K/E gene polymorphisms in a total of 372 subjects were detected by polymerase chain reaction-direct sequencing. All of the subjects were from Linqu County, a high risk area of gastric cancer in Shandong Province of northern China. All cases were initially diagnosed as normal or superficial gastritis at the beginning of this study. After a 5-year follow-up, the cases were subdivided into no progression group (no histological progression, n=137), progression group I (progressed to severe chronic atrophic gastritis, n=194) and progression group II (progressed to low-grade dysplasia, n=41). RESULTS: In all 372 subjects, the frequencies of KK, KE or EE genotype of ICAM-1 K469E were 50.5%, 39.2% and 10.2%, respectively. No significant differences were observed in the ICAM-1 469K/E genotype frequencies between the progression group I and no progression group (P>0.05). The frequencies of KK genotype (68.3%) were significantly higher in the progression group II than in the no progression group (49.6%, P=0.035), and also than in the progression group I (47.4%, P=0.015). An increased risk of the progressing to dysplasia from normal or superficial gastritis was found in the individuals with ICAM-1 469KK genotype [odds ratio (OR)=2.21, 95%CI, 1.10-4.42]. CONCLUSION: ICAM-1 469K/E gene polymorphisms are significantly associated with the risk of gastric low-grade dysplasia, but not related with severe chronic atrophic gastritis in a population with high risk of gastric cancer in Linqu County, Shandong Province, China. PMID- 22780973 TI - [The mRNA expression of BRCA1, ERCC1, TUBB3, PRR13 genes and their relationship with clinical chemosensitivity in primary epithelial ovarian cancer]. AB - OBJECTIVE: To evaluate the expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA and their relationship with clinical chemosensitivity in primary ovarian cancer, and to assess the predictive value of joint detection of both BRCA1 and ERCC1 genes for the treatment of primary ovarian cancer. METHODS: Primary epithelial ovarian tumor samples were collected from 46 patients who underwent cytoreductive surgery. Real-time quantitative PCR was used to analyze the relative expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA in those cases. The correlation of clinical chemosensitivity and the test results was statistically analyzed. The efficacy of the joint prediction of clinical chemosensitivity by combining the two drug resistance gene detection was evaluated. RESULTS: The BRCA1 mRNA relative expression logarithm in the clinical-resistant group was 0.673+/-2.143, and clinical-sensitive group -1.436+/-2.594 (P=0.008). The ERCC1 mRNA relative expression logarithm in the clinical-resistant group was -0.529+/-1.982 and clinical-sensitive group -3.188+/-2.601 (P=0.001). BRCA1 and ERCC1 expression level is negatively correlated with platinum-based chemosensitivity. The PRR13 expressions in the two groups were not significantly different (P=0.074), and the TUBB3 expressions between the two groups were also not significantly different (P=0.619). When the intercept point value BRCA1 mRNA expression logarithm was 0.6, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 73.3%, 75.0%, 84.6% and 60.0%, respectively, with the best comprehensive assessment. When the intercept point value of ERCC1 mRNA expression logarithm was -1, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 80.0%, 68.8%, 82.8% and 64.7%, respectively, with the best comprehensive assessment. The combination detection of BRCA1 and ERCC1 can improve the chemotherapeutic sensitivity, specificity, positive predictive value and negative predictive value to 86.7%, 68.8%, 83.9% and 73.3%, respectively. CONCLUSIONS: BRCA1 and ERCC1 mRNA expression has a negative correlation with the clinical sensitivity of platinum based chemotherapy. Combination detection of the two drug-resistance associated genes can improve the predictive efficacy of ovarian cancer chemosensitivity and beneficial to individual treatment of ovarian cancer. PMID- 22780974 TI - [Displacement of the silver clips in surgical cavity based on four-dimensional CT images for patients undertaking external-beam partial breast irradiation after breast-conserving surgery]. AB - OBJECTIVE: To explore the displacement of the selected clips and the center of the geometry consisted of all the clips in the surgical cavity measured on the basis of four-dimensional computed tomography (4D-CT) simulation images. METHODS: Fourteen breast cancer patients after breast-conserving surgery were recruited for external beam partial-breast irradiation (EB-PBI), and received large aperture CT simulation. The 4D-CT image data sets were collected when the patient was in the free breathing state. Using the Varian Eclipse treatment planning system, the selected four clips in the cavity were separately delineated on the CT images from 10 phases of the breath cycle, and all of the clips in the cavity were marked to obtain the geometry. Then the displacement of the four selected clips and the center of the geometry in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were measured. The differences of the displacement were compared. RESULTS: The displacements in the AP and SI directions were always greater than the displacement in LR direction for the same selected clip. The difference of the displacements in the same direction of the different selected clips was not statistically significant (P>0.05). The displacements of the geometry center consisted of all of the clips in the LR, AP, SI directions were (1.34+/-0.39) mm, (2.01+/-1.02) mm and (1.89+/-1.03) mm, respectively, and the difference of the displacements between LR and AP, LR and SI were all statistically significant (P<0.05). In the same directions (LR, AP and SI), the displacement of geometry center was always greater than the displacement of the selected clips, and the difference except SI direction was all statistically significant (P<0.05). In the SI direction, the association between the displacement of geometry center and the upper clip, geometry center and the lower clip was statistically significant (P<0.05). CONCLUSION: When the target for EB-PBI is defined on the basis of 4D-CT simulation images, the displacement of the selected clips at the border of the surgical cavity is not qualified to substitute the displacement of the target defined basing on all of the clips in the surgical cavity. PMID- 22780975 TI - [Expression and significance of phosphorylated Girdin in breast cancer]. AB - OBJECTIVE: To detect the expression of phosphorylated girdin (p-girdin) in breast cancer and its association with pathological characteristics and molecular subtypes of breast cancer. METHODS: Immunohistochemical SP staining was used to investigate the expression of p-girdin in 27 cases of lobular hyperplasia of mammary gland, 61 cases of ductal carcinoma in situ (DCIS), and 94 cases of non special type invasive carcinoma (IDC-NOS) of breast. RESULTS: p-girdin was located in the cell cytoplasm and (or) nuclei in breast cancer. There was statistically a very significant difference among lobular hyperplasia, DCIS and IDC-NOS (chi2=26.724, P<0.001). Its cytoplasmic and nuclear reactivity were 25.9% (7/27), 39.3% (24/61), and 66.0% (62/94), respectively. The expression of p girdin was positively associated with pathologic stage (r=0.204, P=0.049), lymph node metastasis (r=0.212, P=0.041) and HER2/neu (r=0.248, P=0.016). But no significant association was identified between p-girdin expression and histological grade (r=-0.015, P=0.918), age of patients (r=-0.011, P=0.918), tumor size (r=0.075, P=0.471), ER(r=0.071, P=0.498), PR (r=-0.050, P=0.634). Mann Whitney test showed that p-girdin expression in luminal A, luminal B, triple negative and HER-2(+) type was significantly different (chi2=14.017, P=0.003). Among the four types, its positive rate was 55.8% (24/43), 95.8% (23/24), 66.7% (10/15), and 41.7% (5/12), respectively. CONCLUSIONS: p-Girdin expression is closely correlated with the malignant progression of breast cancer. Its expression may have clinical value as a new target for the treatment of breast cancer. PMID- 22780976 TI - [Clinicopathological and molecular genetic characteristics of childhood diffuse large B cell lymphoma]. PMID- 22780977 TI - [Clinical outcomes and selection conditions of three-field lymph node dissection for thoracic esophageal squamous cell carcinoma]. AB - OBJECTIVE: To analyze the efficiency of cervical lymph node metastasis dissection and postoperative morbidity after selective three-field lymph node dissection (3FLND) for thoracic esophageal squamous cell carcinoma, and explore the proper selection conditions. METHODS: According to the conditions as follows: systemic evaluation, tumor T staging, tumor location, cervical CT and ultrasonography and the number of lymph nodes metastases, 85 patients with thoracic esophageal squamous cell carcinoma were selected and received 3FLND. RESULTS: In the same period 45.5% (85/187) of the patients received 3FLND selectively based on the conditions. The rate of the cervical lymph nodes metastasis was 40.0% (34/85). The rate of the cervical positive lymph nodes of the upper, middle and lower thoracic esophageal carcinomas with enlarged lymph nodes suggested by cervical CT and ultrasonography was 68.4% (13/19), 41.7% (20/48) and 16.7% (1/6), respectively. Twelve patients with upper thoracic esophageal carcinoma with enlarged lymph nodes unrevealed by cervical CT and ultrasonography showed no histopathological lymph node metastasis. In the same period 17.1% (32/187) of the patients were selectively not undergone three-field lymph node dissection. The cervical lymph node metastasis rates in patients with upper and middle mediastinal lymph node metastasis were 79.3% (23/29) and 58.6% (17/29), significantly higher than 8.9% (5/56) and 7.1% (4/56) in the patients without upper and middle mediastinal lymph node metastasis (P<0.05). There was no in hospital mortality in the group. The incidence of pulmonary complications and over-all postoperative morbidity was 24.7% and 42.4%, respectively. CONCLUSIONS: Selective 3FLND based on certain conditions can reduce the risk of postoperative morbidity and improve the efficiency of metastatic cervical lymph node dissection in thoracic esophageal squamous cell carcinoma. The thoracic tracheoesophageal groove positve lymph node indicated by CT scans should be one of selective conditions for 3FLND. The upper thoracic esophageal carcinoma should selectively receive 3FLND. The selection standards should be more strict for the lower thoracic esophageal carcinoma. PMID- 22780978 TI - [Therapeutic effects and prognostic factors for the limited-stage small cell lung cancer treated with multidisciplinary therapy]. AB - OBJECTIVE: To study the differences of objective response rate (ORR), side effects and survival among patients with limited-stage small cell lung cancer (LD SCLC), who received concurrent chemoradiotherapy, sequential chemoradiotherapy or chemotherapy alone, and to analyze the influencing factors on their survival. METHODS: One hundred and sixty-six patients diagnosed as LD-SCLC in Peking Union Medical College Hospital from January 2000 to December 2009 were included in this study. The differences of objective response rates, side effects and survival rates were analyzed by chi2 test. Kaplan-Meier test was used to calculate the overall survival (OS) and progress-free survival (PFS). Cox regression was used to detect the influencing factors on survival time of the patients. RESULTS: The patients were divided into three groups: concurrent chemoradiotherapy (49 cases), sequential chemoradiotherapy (62 cases) and chemotherapy alone (55 cases). The chemotherapy was based on CE/EP regimen, with an average cycle of 5.2. Radiotherapy was of a common or 3-dimensional conformal technology, for regular segmentation irradiation with an average dose of 49.6 Gy. The total ORR was 73.4%, OS and PFS were 22.9 months and 10.8 months, 1, 3, 5-year survival rates were 82.7%, 31.8%, 18.6%, respectively. For the concurrent group, sequential group and chemotherapy alone group, the ORR was 89.4%, 67.2% and 66.0%, respectively. Compared the chemotherapy alone group and concurrent group with the sequential group, there were significant differences (P<0.05). For the concurrent group, sequential group and chemotherapy alone group, the median OS was 29.7 months, 22.6 months, and 19.5 months; the median PFS was 12.7 months, 10.8 months, and 9.8 months, respectively, with a non-significant difference between each two groups (P>0.05). For the concurrent group, sequential group and chemotherapy alone group, the 1-year survival rates were 91.1%, 86.3%, and 65.6%, the 3-year survival rates were 44.2%, 28.3% and 22.8%, and the 5-year survival rates were 24.2%, 21.4% and 11.1%, respectively, with significant differences among them (P<0.05). The major side effects were myelosuppression, gastrointestinal reactions, radiation pneumonia and radiation esophagitis. For the concurrent group, sequential group and chemotherapy alone group, the incidence of myelosuppression were 84.4%, 76.8% and 60.0%, respectively, with a significant difference (P=0.008) between the concurrent group and chemotherapy alone group. For the concurrent group and sequential group, the incidences of radiation pneumonia were 22.2% and 22.9%, with a non-significant difference (P=0.940). The incidences of radiation esophagitis were 47.2% and 16.7%, respectively, with a significant difference (P=0.002). Multivariate analysis showed that OS was significantly associated with gender (P=0.018) and ECOG score (P=0.009), and PFS was significantly associated with gender (P=0.050). CONCLUSIONS: For LD-SCLC, concurrent chemoradiotherapy can significantly increase the objective response rate. Concurrent chemoradiotherapy and sequential chemoradiotherapy compared with chemotherapy alone can extend survival, and concurrent chemoradiotherapy is better, but the differences among the three regimens are not significant. Gender and ECOG score are important influencing factors of survival. PMID- 22780980 TI - [Comparison of the effect of palonosetron versus tropisetron in prevention of vomiting in patients receiving high dose cisplatin-based chemotherapy]. AB - OBJECTIVE: To evaluate the efficacy and toxicity of palonosetron for prevention of vomiting induced by high dose cisplatin-based chemotherapy. METHODS: One hundred and twenty-eight patients received tropisetron 5 mg plus dexamethasone 10 mg at the first cycle or palonosetron 0.25 mg plus dexamethasone 10 mg, respectively, each administered 30 min before the initiation of high dose cisplatin-based chemotherapy. To observe the remission rate of acute emetic episodes and delayed emetic episodes, adverse effects and daily food-intake in the patients after the chemotherapy. RESULTS: The complete response (CR) rates for acute vomiting were not significantly different between the tropisetron and palonosetron cycles (75.8% vs. 79.7%, P>0.05). The complete control rate of delayed vomiting in the palonosetron cycle was significantly higher than that in the tropisetron cycle (70.3% vs. 50.8%, P<0.01). The food-intake decrease rate of palonosetron cycle was 18.8%, significantly lower than the 53.1% of the tropisetron cycle (P<0.05). The toxicity in the two cycles was similar and no grade 3-4 toxicity was observed. CONCLUSIONS: Palonosetron is superior to tropisetron with a lower remission rate of delayed emesis induced by high dose cisplatin-based chemotherapy and with tolerable toxicity. Moreover, the apparent emesis control of palonosetron treatment seems to provide an adequate food-intake in these patients. PMID- 22780979 TI - [Comparison of the efficacy of CCCG-97 and BFM-90 protocols in the treatment for children with mature B-cell non-Hodgkin's lymphoma]. AB - OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of the CCCG-97 and BFM-90 protocols in the treatment of pediatric patients with B-cell non-Hodgkin's lymphoma (B-NHL) retrospectively, and to explore the optimal therapeutic strategy. METHODS: Forty-five consecutive untreated patients (age of 18 years or less) with newly diagnosed B-NHL (including Burkitt Lymphoma and diffuse large B-cell lymphoma), treated in our hospital between July 1999 and December 2008 were enrolled in this study. The patients were classified into 2 groups by different protocols. From July 1999 to December 2004, twenty-one 3- to 13.8-year-old children were enrolled in the CCCG-97 group, with 1 in stage I/II, and 20 in stage III/IV(St Jude staging). From January 2005 to December 2008, twenty-four 2.8- to 14.1-year-old cases were enrolled in the BFM-90 group, with 3 in stage I/II, and 21 in stage III/IV (St Jude staging). The survival rates were evaluated by Kaplan-Meier analysis. RESULTS: Forty of the 45 patients (88.9%) reached complete response (CR) after 2 courses of chemotherapy. In the CCCG-97 group, the CR rate was 95.2% (20/21 pts), while that in the BFM-90 group was 83.3% (20/24 pts). At a median follow-up time of 62 (17 to 131) months, the 5 year event-free survival (EFS) was 71.8% for all patients, and 69.1% for Stage III/IV, respectively. In the CCCG-97 group, the 3-year EFS was 76.2%. In the BFM 90 group, it was 75.0%. There was no significant difference in survival rates between the CCCG-97 and BFM-90 groups (P=0.975). Unfavorable events recorded were as follows: Death of progression before achieving CR during induction therapy in 4 cases, and relapse after achieving CR in 6 cases. The relapse rates were 19.0% (4/21 pts) in the CCCG-97 group and 8.3% (2/24 pts) in the BFM-90 group, with a non-significant statistical difference (P=0.292). Major toxicities were myelosuppression and mucositis, especially in the BFM-90 group, but were tolerable and manageable. five patients in the BFM-90 group received rituximab, 2 patients (Stage III) achieved CR, while the other 3 patients (Stage IV) had progressive disease or relapse. CONCLUSIONS: Short-pulse and intensive chemotherapy, stratified according to stage of disease, can improve the survival rate of pediatric mature B-NHL. The efficacy of the CCCG-97 protocol and BFM-90 protocol is comparable and the toxicity is tolerable. PMID- 22780981 TI - [Clinical analysis of 36 cases of esophageal mucoepidermoid carcinoma]. AB - OBJECTIVE: To review the clinical characteristics, diagnosis, treatment and prognosis of esophageal mucoepidermoid carcinoma (MEC). METHODS: Clinical data of 36 patients with pathologically confirmed esophageal MEC who received surgical treatment in Cancer Hospital of Shantou University Medical College from Jan 1991 to Jun 2010 were retrospectively analyzed. The survival analysis was performed using Kaplan-Meier method. RESULTS: Of the 4253 patients diagnosed as esophageal cancer during the same time in our center, only 36 had esophageal MEC, accounted for 0.8%. This group included 27 men and 9 women ranging in age from 40 to 78 years (median 58 years). Esophageal MEC showed similar clinical symptoms, radiological and endoscopic features to esophageal squamous cell carcinoma (ESCC). Of the 20 cases who received preoperatively endoscopic biopsy, 18 were misdiagnosed as ESCC and 2 were misdiagnosed as esophageal adenosquamous carcinoma. The mean follow-up duration of this series was 38.8 months (3-142 months). 22 patients died of the disease during the follow-up period, 12 were still alive and 2 were lost of follow-up. The median survival time (MST) of the 36 patients was 29.0 months, and the 1-, 2-, 3-, and 5-year overall survival rates (OS) were 80.6%, 57.1%, 34.4%, 25.8%, respectively. CONCLUSIONS: Esophageal MEC is a rare disease and prone to be misdiagnosed by endoscopic biopsy. Surgical resection is the primary treatment but the prognosis is poor. PMID- 22780982 TI - [Analysis of prognostic factors for gastric stump cancer]. AB - OBJECTIVE: To investigate the independent prognostic factors of long-term survival for gastric stump cancer after radical resection. METHODS: The clinicopathological and follow-up data of 63 patients with gastric stump cancer undergoing surgical treatment from January 1996 to December 2006 in our hospital were analyzed retrospectively, including age, gender, types of reconstruction, tumor location, histological types, TNM stages, surgical treatment, prognosis and etc. The survival was estimated using Kaplan-Meier method and compared using log rank test. The effect of independent factors on prognosis was determined by Cox regression multivariate analysis. RESULTS: Radical resection was performed in 35 patients, including combined multiple organ resection (n=16). Surgery was palliative in 28 patients. All the 63 patients were followed up. The median survival time of these 63 patients was 21 months, and the overall 1-, 3-, 5-year survival rates were 76.2%, 31.7% and 18.8%, respectively. Univariate and multivariate analysis showed that surgical procedure, clinical stage and histological type were independent prognostic factors of gastric stump cancer, while age, gender, type of reconstruction and tumor location were not significantly correlated with prognosis. CONCLUSIONS: Radical resection, clinical stage and histological type are main prognostic factors for gastric stump cancer. Radical resection is an effective way to prolong the postoperative survival time in patients with gastric stump cancer, especially in the early stage. PMID- 22780983 TI - Sublingual nucleotides and immune response to exercise. AB - Evidence exists regarding the potential role of exogenous nucleotides as regulators of the immune function in physically active humans, yet the potential use of nucleotides has been hindered by their low bioavailability after oral administration. We conducted a double-blind, placebo-controlled, randomized trial to assess the effect of sublingual nucleotides (50 mg/day) on salivary and serum immunity indicators as compared to placebo, both administered to healthy males aged 20 to 25 years for 14 days. Sublingual administration of nucleotides for 14 days increased serum immunoglobulin A, natural killer cells count and cytotoxic activity, and offset the post-exercise drop of salivary immunoglobulins and lactoferrin (P < 0.05), with no adverse effects reported. No significant differences in fasting salivary antimicrobal proteins (alpha-amylase, lysozyme and lactoferrin) were found before or after the treatment (P > 0.05). It seems that sublingual administration of nucleotides for two weeks considerably affected immune function in healthy males. PMID- 22780984 TI - Frailty: enhancing the known knowns. PMID- 22780985 TI - Another step forward in relating facial and brain dysmorphologies associated with prenatal alcohol exposure. PMID- 22780986 TI - A clarion call for nurse-led SBIRT across the continuum of care. AB - This commentary discusses the impact of the study by Broyles and colleagues (2012) that reported on hospitalized patients' acceptability of nurse-delivered screening, brief intervention, and referral to treatment (SBIRT). This cross sectional survey study assessed patient acceptability for and comfort with nurse delivered SBIRT. The majority (95%) of inpatients found it acceptable for the nurse to ask about and/or discuss alcohol use during their hospitalization. This is a significant finding, as hospitals in the United States consider whether and how to implement The Joint Commission's performance measures related to SBIRT for hospitalized patients. The findings related to subgroups of patients who are more accepting of SBIRT and those who expressed some degree of discomfort highlight the importance for individualized patient-centered approaches. This study raises several important implications for nurse-delivered SBIRT. First, intensive efforts must be directed to enhancing the knowledge and competence of healthcare providers in general, and the current and future nursing workforce in particular, related to alcohol use and evidence-based care for patients who are drinking alcohol above recommended limits. Second, registered nurses, working to the full extent of their education and licensure are in key roles as members of the interdisciplinary team to provide cost-effective care at the bedside and across the continuum of care. Nurse-led SBIRT implementation models could help bridge the curricular gap and promote widespread and sustained integration of SBIRT as standard nursing care across all specialties and practice settings. PMID- 22780988 TI - Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases. AB - BACKGROUND: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. METHODS: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. RESULTS: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. CONCLUSIONS: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information. PMID- 22780989 TI - Cohesin regulates tissue-specific expression by stabilizing highly occupied cis regulatory modules. AB - The cohesin protein complex contributes to transcriptional regulation in a CTCF independent manner by colocalizing with master regulators at tissue-specific loci. The regulation of transcription involves the concerted action of multiple transcription factors (TFs) and cohesin's role in this context of combinatorial TF binding remains unexplored. To investigate cohesin-non-CTCF (CNC) binding events in vivo we mapped cohesin and CTCF, as well as a collection of tissue specific and ubiquitous transcriptional regulators using ChIP-seq in primary mouse liver. We observe a positive correlation between the number of distinct TFs bound and the presence of CNC sites. In contrast to regions of the genome where cohesin and CTCF colocalize, CNC sites coincide with the binding of master regulators and enhancer-markers and are significantly associated with liver specific expressed genes. We also show that cohesin presence partially explains the commonly observed discrepancy between TF motif score and ChIP signal. Evidence from these statistical analyses in wild-type cells, and comparisons to maps of TF binding in Rad21-cohesin haploinsufficient mouse liver, suggests that cohesin helps to stabilize large protein-DNA complexes. Finally, we observe that the presence of mirrored CTCF binding events at promoters and their nearby cohesin-bound enhancers is associated with elevated expression levels. PMID- 22780990 TI - Switching mechanisms in flexible solution-processed TiO2 memristors. AB - Memristors are emerging as unique electrical devices with potential applications in memory, reconfigurable logic and biologically inspired computing. Due to the novelty of these devices, the complete details of their switching mechanism is not yet well established. In this work, the switching mechanism of our solution processed titanium dioxide-based memristor is investigated by studying how variations in the device area and film thickness affect electrical behavior and correlating these behavioral changes to proposed switching mechanisms. The conduction path of the switching is also investigated through electrical characterization of devices both before and after physically cutting the devices in half, as well as through infrared imaging of the devices during operation. The results suggest that the electrical behavior of these devices is dominated by a localized, charge-based phenomenon that exhibits a dependence on device area. PMID- 22780991 TI - Dendroscope 3: an interactive tool for rooted phylogenetic trees and networks. AB - Dendroscope 3 is a new program for working with rooted phylogenetic trees and networks. It provides a number of methods for drawing and comparing rooted phylogenetic networks, and for computing them from rooted trees. The program can be used interactively or in command-line mode. The program is written in Java, use of the software is free, and installers for all 3 major operating systems can be downloaded from www.dendroscope.org. [Phylogenetic trees; phylogenetic networks; software.]. PMID- 22780992 TI - The real you? The role of visual cues and comment congruence in perceptions of social attractiveness from facebook profiles. AB - The purpose of this study was to examine the effects of social cues in self presentations and the congruence of other-generated comments with the self presentation in people's evaluations of a profile owner. A 2 (level of social cues: high vs. low) * 2 (congruent vs. incongruent) * 2 (order) * 2 (multiple messages) mixed-subject experiment was conducted with 104 college students. The results showed that a profile owner was perceived less socially attractive when other-generated comments were incongruent with the profile owner's self presentation. No matter how people package themselves with extravagant self presentations, it cannot be very successful without validation from others. Interestingly, an interaction effect between congruence and the level of social cues suggested that perceived popularity was low in the incongruent condition regardless of level of social cue. Theoretical and practical implications were also discussed. PMID- 22780993 TI - Microblogging, online expression, and political efficacy among young chinese citizens: the moderating role of information and entertainment needs in the use of weibo. AB - In 2011, China's Internet population reached over half a billion users and the popular Twitter-like social networking service, Weibo, has been adopted by half of the users since its launch in August 2009. Given the potential of the Internet to facilitate a civic culture in the authoritarian state, the use of Weibo and its effects on citizens' political attitudes and behaviors are of important concern. A survey of 499 Weibo users found that intensity of use was related to increased willingness to express opinions about government and politics, the perception that one has the ability to participate in politics, and feelings that the government is not responsive to the demands of citizens. Moreover, the above relationships were moderated by the motivations of Weibo use, such that information motives strengthened the relationships while entertainment motives weakened the relationships. PMID- 22780994 TI - Human flesh search: a supplemental review. AB - Human flesh search (HFS), a phenomenon that has recently emerged over the Internet, represents the interaction between the virtual and real worlds. The term "HFS" is equivalent to "cyber manhunt" in the West, although there were more large-scale HFS events reported in the East recently. While the majority of academic articles on HFS have focused on the Chinese context, the phenomenon has also been reported in many countries and involves diverse issues such as the controversy between privacy violation and public opinion. Based on 16 HFS references, a review paper by Chen and Sharma summarizes core issues on growth, incidents, distinctive attributes, key benefits and drawbacks, findings, and research gaps and opportunities. Echoing their call for a global HFS context, the current article provides a Taiwanese HFS context based on 32 reported incidents in Taiwan. To conduct an incremental HFS review, this study expands the reference base to 33 carefully selected academic articles from China and Taiwan. The review findings range from 6 derived HFS perspectives supplementing each article, 12 frequently mentioned HFS concepts, and 4 additional research directions. The resulting comprehensive knowledge of HFS, along with that contributed by Chen and Sharma, can be considered a useful reference framework for future HFS studies and policy making. PMID- 22780995 TI - Explaining the use of text-based communication media: an examination of three theories of media use. AB - The present study examined the factors associated with individuals' use of three different text-based communication media: e-mail, cell-phone texting, and Facebook Wall postings. Three theoretical perspectives, including media richness theory, uses and gratifications, and perceived network effects, were examined. Using data from a survey of college students (N=280), the study found that the theoretical constructs from these theories play different roles when applied to different technologies. The results suggest that a simultaneous consideration of technological attributes, users' motivations, and social circumstances in which users select and use the technology is useful for fully understanding the dynamics of the selection and the use of a given technology. PMID- 22780996 TI - Exploring replay value: shifts and continuities in user experiences between first and second exposure to an interactive story. AB - While replay value is a common term in interactive entertainment, psychological research on its meaning in terms of user experiences is sparse. An exploratory experiment using the interactive drama "Facade" was conducted (n=50) to examine shifts and continuities in entertainment-related user experiences between first and second exposure to the same system. A questionnaire with brief scales measuring various user-experience dimensions (interaction-related facets such as usability, flow, and presence, as well as narrative-related facets such as suspense and curiosity) was administered after the first and the second round of exposure. Findings suggest that replay produces gains in action-related experience components such as presence and effectance, whereas narrative-related experiences such as curiosity and suspense remain stable across exposures. Implications for theorizing on interactive entertainment experiences are discussed. PMID- 22780999 TI - Heat-processed ginseng enhances the cognitive function in patients with moderately severe Alzheimer's disease. AB - OBJECTIVES: Ginseng has been reported to improve cognitive function in animals and in healthy and cognitively impaired individuals. In this study, we investigated the efficacy of a heat-processed form of ginseng that contains more potent ginsenosides than raw ginseng in the treatment of cognitive impairment in patients with moderately severe Alzheimer's disease (AD). METHODS: Forty patients with AD were randomized into one of three different dose groups or the control group as follows: 1.5 g/day (n = 10), 3 g/day (n = 10), and 4.5 g/day (n = 10) groups, or control (n = 10). The Alzheimer's Disease Assessment Scale (ADAS) and Mini-Mental State Examination (MMSE) were used to assess cognitive function for 24 weeks. RESULTS: The treatment groups showed significant improvement on the MMSE and ADAS. Patients with higher dose group (4.5 g/day) showed improvements in ADAS cognitive, ADAS non-cognitive, and MMSE score as early as at 12 weeks, which sustained for 24-week follow-up. DISCUSSION: These results demonstrate the potential efficacy of a heat-processed form of ginseng on cognitive function and behavioral symptoms in patients with moderately severe AD. PMID- 22781000 TI - Progressive respiratory insufficiency in the absence of cardiac disease in late stage Duchenne muscular dystrophy. PMID- 22781002 TI - Simple and effective approach for the treatment of traumatic wounds in non diabetic patients: a prospective open study. AB - Infection is one of the most important obstacles in the wound-healing process. Conventional methods used for the treatment of wound infections have their own limitations and hence, are difficult to control. If infection is not addressed well in time, it will further increase morbidity and cost of treatment. An attempt was made to develop a simple and effective treatment modality by using citric acid as the sole antimicrobial agent to control bacterial infections of traumatic wounds. A total of 259 cases of traumatic wounds infected with a variety of bacteria were investigated for culture and susceptibility, and susceptibility to citric acid. Citric acid ointment (3%) was applied to traumatic wounds to determine its efficacy in their treatment of traumatic wounds. In a culture and susceptibility study, a total of 369 aerobic bacteria and 7 fungi were isolated, with Staphylococcus aureus (30.31%) being the most common isolate and ciprofloxacin (61.43%) being the most effective agent. All the isolates were found to be inhibited by citric acid in in vitro studies (minimum inhibitory concentration--500-2500 ug/ml). Citric acid ointment was found effective in controlling infections. Out of 259 cases, 244 (around 95%) were healed completely in 5-25 applications of 3% citric acid. As citric acid has antibacterial activity and wound-healing property; hence it is the best alternative for the treatment of traumatic wounds. Besides these properties, citric acid has no adverse effects and it is a good dressing agent. PMID- 22781003 TI - Primary care research priorities in low back pain: an update. AB - STUDY DESIGN: Survey report. OBJECTIVE: To reassess an existing list of research priorities in primary care low back pain (LBP) and to develop a new research agenda. SUMMARY OF BACKGROUND DATA: Primary care LBP researchers developed an agenda of research priorities in 1997 at an international conference. In 2009, a survey was conducted to re-evaluate the 1997 research priorities and to develop a new research agenda. METHODS: Two-phase, Internet-based survey of participants in one of the LBP primary care research fora. The first phase collected information on importance, feasibility, and progress for the 1997 priorities; during this phase, the respondents were also asked to list the 5 most important current primary care-relevant LBP research questions. The second phase ranked these current research priorities. RESULTS: A total of 179 persons responded to the first phase, representing 30% of those surveyed. Rankings of the 1997 priorities were somewhat similar compared with 2009, although research on beliefs and expectations and improving the quality of LBP research became more important, and research on guidelines and psychosocial interventions became less important. Organizing more effective primary care for LBP, implementing best practices, and translating research to practice were ranked higher compared with 1997. Most priorities were also ranked as relatively feasible. The new agenda was similar, and included subgroup-based treatment and studies on causes and mechanisms of LBP as new top priorities. CONCLUSION: Changes in research priorities seem to reflect recent advances, new opportunities, and limitations in our ability to improve care. PMID- 22781001 TI - Sphingosine-1-phosphate lyase expression in embryonic and adult murine tissues. AB - Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in immunity, inflammation, angiogenesis, and cancer. S1P lyase (SPL) is the essential enzyme responsible for S1P degradation. SPL augments apoptosis and is down-regulated in cancer. SPL generates a S1P chemical gradient that promotes lymphocyte trafficking and as such is being targeted to treat autoimmune diseases. Despite growing interest in SPL as a disease marker, antioncogene, and pharmacological target, no comprehensive characterization of SPL expression in mammalian tissues has been reported. We investigated SPL expression in developing and adult mouse tissues by generating and characterizing a beta-galactosidase-SPL reporter mouse combined with immunohistochemistry, immunoblotting, and enzyme assays. SPL was expressed in thymic and splenic stromal cells, splenocytes, Peyer's Patches, colonic lymphoid aggregates, circulating T and B lymphocytes, granulocytes, and monocytes, with lowest expression in thymocytes. SPL was highly expressed within the CNS, including arachnoid lining cells, spinal cord, choroid plexus, trigeminal nerve ganglion, and specific neurons of the olfactory bulb, cerebral cortex, midbrain, hindbrain, and cerebellum. Expression was detected in brown adipose tissue, female gonads, adrenal cortex, bladder epithelium, Harderian and preputial glands, and hair follicles. This unique expression pattern suggests SPL has many undiscovered physiological functions apart from its role in immunity. PMID- 22781004 TI - Neurogenic bladder associated with pure cervical spondylotic myelopathy: clinical characteristics and recovery after surgery. AB - STUDY DESIGN: Retrospective study. OBJECTIVE: To examine the prevalence of lower urinary tract symptoms (LUTS) and neurogenic bladder (NB), and surgical outcomes in pure cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: The inclusion of various types of cervical diseases, NB, and no obvious definition of NB provided the wide range of NB prevalence frequency among previous reports. METHODS: Of the 220 operated patients with cervical myelopathy, 54 were selected by excluding other cervical and/or concomitant diseases contributing to LUTS. All patients with LUTS were referred to urologists and recommended to undergo urodynamic study (UDS). The presence of NB was judged by abnormal findings of UDS according to the most recent criteria and a congruity between LUTS and the course of cervical myelopathy. Patients were divided into 4 groups: no symptoms, positive symptoms without UDS examination, positive symptoms with positive NB, and positive symptoms with negative NB. Evaluation scores were compared among the groups before and after surgery. RESULTS: There were no particular LUTS in NB patients. Prevalence of LUTS was 53.7% and that of NB was at least 20.4% in the patients with pure cervical spondylotic myelopathy. The scores of all 4 groups improved after surgery (P < 0.05); however, the recovery rate of NB group (47.1%) was the worst among the groups (no-symptoms group, 69.3%; negative-NB group, 53.5%; and positive symptoms without UDS group, 57.1%). Preoperative part scores showed no difference among the groups, whereas NB group demonstrated lower scores in finger and lower extremity postoperatively. A post hoc analysis confirmed a significantly poorer recovery rate related to the NB group only in the lower extremities. CONCLUSION: This study is the first to describe the prevalence of LUTS and NB according to the most recent criteria in patients with pure cervical spondylotic myelopathy, which demonstrated that neurological functions in NB patients may recover; however, the extent will be limited to two-thirds of those in patients with no-NB; moreover, the remaining symptoms derive from poor lower limb function. PMID- 22781005 TI - Surgical treatment of C3 and C4 cervical radiculopathies. AB - STUDY DESIGN: Case series study. OBJECTIVE: To report the results of surgical intervention in a series of patients with high cervical radiculopathy. SUMMARY OF BACKGROUND DATA: Although midcervical (C5-C7) radiculopathy is common and well recognized, high cervical (C3 and C4) radiculopathy is relatively rare and can be missed clinically. To our knowledge, there are few reports regarding the operative treatment of high cervical radiculopathy. METHODS: Two spine surgeons independently reviewed the charts and radiographs of all patients with high cervical radiculopathy or myeloradiculopathy that were surgically treated by the senior author. Dates of inclusion were from July 1997 to March 2008. All patients were observed for either a minimum of 2 years or until they achieved a fusion. Neck Disability Index scores were calculated pre- and postoperatively, when available, and Odom criteria were assessed for all patients. RESULTS: Twenty three patients met the inclusion criteria. The mean follow-up period was 4.2 years (1-11.3 yr). The levels involved were C2-C3 (2 patients), C2-C4 (4 patients), and C3-C4 (17 patients). The most common symptom was suboccipital neck pain/headache with or without radiation to the retroauricular or retro-orbital region (21 patients). Preoperative neuroradiological findings were central stenosis with herniated nucleus pulposus, foraminal stenosis with uncinate hypertrophy or facet arthrosis, spondylolisthesis, and pseudarthrosis. Operative treatments included anterior cervical discectomy and fusion, posterior foraminotomy, posterior laminectomy-foraminotomy with fusion, posterior laminoplasty with fusion, and anterior/posterior combined decompression and fusion. By Odom criteria, 12 had excellent results, 8 had good results, 2 had satisfactory results, and 1 had a poor result. One patient underwent a reoperation for pseudarthrosis. CONCLUSION: Surgical treatment of high cervical radiculopathies resulted in acceptable outcomes. To our knowledge, this is the largest series of this relatively rare condition. PMID- 22781006 TI - Seeing double: a comparison of microstructure, biomechanical function, and adjacent disc health between double- and single-layer vertebral endplates. AB - STUDY DESIGN: Experimental and computational assessment of thickness, porosity, biomechanical behavior, and adjacent disc glycosaminoglycan content in double- and single-layer bony endplate samples harvested from human cadaver spines. OBJECTIVE: To determine if the second layer of bone in double-layer vertebral endplates allows the superficial layer to achieve a more optimal balance between its biomechanical and nutritional functions. SUMMARY OF BACKGROUND DATA: Proper disc health requires the endplate to balance opposing biomechanical and nutritional functions. Previous studies investigating endplate function report seeing double: some endplates have a second layer of bone. However, it remains unclear whether the second layer of bone has any functional advantage. Such information could shed light on the factors that protect against disc degeneration. METHODS: Six lumbar spines were obtained from human cadavers (32-84 yr) and scanned with magnetic resonance imaging. Cylindrical cores that included the endplate and underlying trabecular bone were harvested from the center of the superior vertebral endplates (6 double- and 12 single-layer endplates) and imaged using micro-computed tomography. The thickness and porosity of the bony endplate layers were measured for each core. High-resolution finite element analysis was performed to assess biomechanical behavior. Glycosaminoglycan content within the adjacent nucleus tissue was quantified using the dimethylmethylene blue technique. RESULTS: The superficial layer of the double-layer endplates was 50% thinner (P = 0.009) and tended also to be more porous than single-layer endplates. Strains were higher in thinner endplates; however, the second layer of bone in the double-layer endplates had a stiffening effect so that despite being thinner than single-layer endplates, the superficial layer of the double-layer endplates had a similar risk of damage. After adjusting for age, glycosaminoglycan content was significantly higher in the nucleus tissue adjacent to the double-layer endplates (P = 0.01). CONCLUSION: Compared with single-layer endplates, double-layer endplates seem to permit a more optimal balance between endplate biomechanical and nutritional functions, and may therefore offer a significant protective factor against disc degeneration. PMID- 22781007 TI - Growth of spinal interventional pain management techniques: analysis of utilization trends and Medicare expenditures 2000 to 2008. AB - STUDY DESIGN: Analysis of the growth, utilization trends, and Medicare expenditures of spinal interventional pain management techniques from 2000 through 2008. OBJECTIVE: To evaluate the use of epidural steroid injections, facet joint interventions, and sacroiliac joint interventions, and to analyze the trends of Medicare utilization and expenditures in multiple settings-namely, hospital outpatient departments, ambulatory surgery centers, and physician offices. SUMMARY OF BACKGROUND DATA: There has been an explosive growth of many invasive and noninvasive modalities designed to manage chronic spinal pain. Commonly used interventional techniques include epidural steroid injections, facet joint interventions, and sacroiliac joint interventions. However, their effectiveness and the appropriateness of their application continue to be debated. METHODS: The present article provides an analysis of the growth of spinal interventional techniques, as described earlier, for managing the chronic spinal pain of Medicare beneficiaries from 2000 through 2008. The standard 5% national sample of the Centers for Medicare and Medicaid Services carrier claims that record data from 2000 through 2008 were utilized. Current procedural terminology codes from 2000 through 2008 were used to identify the number of procedures performed each year, as well as trends and expenditures. RESULTS: Medicare recipients receiving spinal interventional techniques increased 107.8% from 2000 through 2008, with an annual average increase of 9.6%, whereas spinal interventional techniques increased 186.8%, an annual average increase of 14.1% per 100,000 beneficiaries. CONCLUSION: The study suggests explosive increases in spinal interventional techniques from 2000 to 2008, with some slowing of growth in later years. PMID- 22781008 TI - Late-onset bowel perforation and iliac artery erosion after prominent anterior spinal instrumentation. AB - STUDY DESIGN: Case report. OBJECTIVE: To report a rare complication of anterior spine surgery and instrumentation. SUMMARY OF BACKGROUND DATA: Anterior spinal fusion and instrumentation are now frequently used for the treatment of a variety of complex spinal disorders. Several authors have discussed the complications of such procedures. Late perforation of large bowel along with erosion of major vessel after anterior spinal instrumentation is a rare occurrence. METHODS: We present a case of 53-year-old woman who presented with unusual abdominal pain and bleeding of the rectum. She had undergone spine surgery for L5 burst fracture 5 years ago. A detailed evaluation showed perforation of rectosigmoid colon and erosion of left common iliac artery by the anterior spine implants. RESULTS: The bowel was repaired and arterial reconstruction was done along with spine implant removal. The patient had complete recovery of symptoms after the treatment. CONCLUSION: Delayed visceral injury with anterior spine surgeries is rare. Early diagnosis is possible with a high degree of suspicion. Meticulous surgical techniques may avoid this complication. PMID- 22781009 TI - Regarding the possibility of anterior vascular injury from the posterior approach to the lumbar disc space: an anatomical study. AB - STUDY DESIGN: Anatomical study with magnetic resonance imaging data. OBJECTIVE: To document the distances between the major retroperitoneal vessels and the anterior lumbar disc spaces; to determine the effect of patient positioning on these relationships; and to discuss ways to deal with vascular injury. SUMMARY OF BACKGROUND DATA: It is well known that there are major vascular structures anterior to the lower lumbar spine. Vascular injury during posterior approaches, however, remains a problem. These anatomical relationships have not been determined in vivo, and there are no data on the effect of turning the patient prone, and onto bolsters. METHODS: A random sampling of 49 women and 48 men was made. All examinations were performed in magnetic resonance scanners operating at 1.5 T. Measurements were made using electronic calipers on axial T2-weighted images. Post hoc studies were done on a smaller number of patients, to determine the effect of prone positioning. RESULTS: At the L4-L5 level, 66% of the common iliac arteries in women and 49% of those in men were within 5 mm of the anterior aspect of the disc space. At L5-S1, these numbers dropped to 23% for women and 19% for men. No relationship between the age of the patient and the distance from disc space to blood vessel was found. There was little change in these measurements between the supine and prone positions. The use of bolsters to decompress the abdominal contents in the prone position did not significantly alter the disc-artery distances. Venous relationships were also documented. CONCLUSION: The lower lumbar spine is confirmed to frequently be very close to the major retroperitoneal vessels. Turning the patient prone and placing the patient on bolsters does not change this relationship. This is part of the reason why vascular injuries may occur during routine lumbar spine surgery. Spine surgeons should be able to recognize and initiate treatment of such injuries. PMID- 22781010 TI - [Associations of exposure to dioxins and polychlorinated biphenyls with diabetes: based on epidemiological findings]. AB - Persistent organic pollutants (POPs) are a group of chemical substances that have the common properties of resistance to biodegradation, wide-range transportation, high lipophilicity, bioaccumulation in fat, and biomagnification in the food chain. POPs are persistent in the environment worldwide and have potential adverse impacts on human health and the environment. Polychlorinated dibenzo-p dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are well known chemicals that are considered as POPs. The association between high-level exposure to dioxins and type 2 diabetes among U.S. Air Force veterans who had been exposed to Agent Orange contaminated with 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) during the Vietnam War was reported in the late 1990s. This association has been supported by similar epidemiologic studies, whose subjects were exposed to high doses of dioxins in their places of work involving phenoxyacid herbicide production and spraying, and in the industrial accident in Seveso, Italy. Recently, low-level exposure to dioxins and PCBs has been reported to be linked to type 2 diabetes. Cross-sectional studies in the U.S. general population and Japanese general population showed that body burden levels of some dioxins and PCBs were strongly associated with the prevalence of type 2 diabetes. Very recently, following these cross-sectional studies, several prospective studies have suggested that low-level exposure to some PCBs predicted the future risk of type 2 diabetes in the general population. Environmental exposure to some dioxins and PCBs, which mainly accumulate in adipose tissue, may play a role in the development of type 2 diabetes. PMID- 22781011 TI - [Regarding the special feature of "the frontline of nanoparticle research": progress of the Study Group on Fibrous and Particulate Substances (SGFPS)]. AB - Among the symposia organized by various study groups in the Japanese Society of Hygiene (JSH), the Study Group on Fibrous and Particulate Substances (SGFPS) presented a symposium entitled "The frontline of nanoparticle research" chaired by Professor Takemi Otsuki (Kawasaki Medical School, Japan) and Dr. Seishiro Hirano (National Institute for Environmental Studies, Japan) on 26 March, 2012, as a part of the program of the 82nd Annual Meeting of JSH in Kyoto, Japan. Special features consist of three presentations given at the above-mentioned symposium. In this article, we introduce the progress of the Study Group on Fibrous and Particulate Substances (SGFPS) from the initial symposium entitled "Asbestos: Science and Society" held at the 76th Annual Meeting of JSH at Ube, Japan to the last above-mentioned symposium in Kyoto. The health-related issues caused by exposure to fibrous materials such as asbestos and also particulated substances such as nanoparticles will be lasting in the future and researchers including our study group have to make their best efforts to resolve these problems and to reduce health impairments due to exposure to environmental fibrous and particulated substances. PMID- 22781012 TI - [Environmental exposure to silver and its health effects]. AB - Silver (Ag) possesses a well-known antibacterial activity and has been used for medical treatment and cosmetics such as wound dressing and deodorant powders. Occupational Safety and Health Administration (OSHA) and Mine Safety and Health Administration (MSHA) proposed that the permissible exposure limit (PEL) for both metallic and most soluble Ag compounds should be 0.01 mg/m3. Argyria and argyrosis are known to be caused by deposition of insoluble Ag in the dermis and cornea/conjunctiva. However, the metabolic behavior and biological roles of Ag have not been well characterized in mammals. Ag can be absorbed into the systemic circulation from drinking water, and also through parenteral routes such as inhalation and dermal exposure. Experimental studies have demonstrated that Ag+ induces and binds to metallothionein I and II (MTs), which are cysteine-rich proteins, in cells. MTs are major cytoplasmic metal binding proteins and thereby reduce cellular damage caused by toxic heavy metals including Ag. Profiles of Ag distribution in MTs and other Ag-binding proteins can be determined using high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS). This technique directly provides information on the intracellular behavior of Ag, which is important for elucidating the mechanism underlying Ag toxicity. Silver nanoparticles (AgNPs) are also commercially used mainly as antimicrobial agents. Despite the widespread use of AgNPs, relatively few studies have been undertaken to evaluate the health effects of AgNP exposure. In the present paper, we discuss the absorption, toxicodynamics, and metabolism of both Ag and AgNPs in mammals and their health effects. PMID- 22781013 TI - [Significance of comprehensive gene expression analysis for evaluation of biological effects of manufactured nanomaterials]. AB - The industrial applications of manufactured nanomaterials (MNs) are expected to be extended to next-generation devices. On the other hand, concern over the effects of MNs on human health has risen owing to advances in the development of nanotechnology. Indeed, little is known about the mechanism of action of MNs. The New Energy and Industrial Technology Development Organization of Japan (NEDO) launched a new research project entitled "Evaluating risks associated with manufactured nanomaterials (P10024)" in 2006. The project demonstrated no adverse effects of MN inhalation exposure on the rat lungs, as determined by histopathological examination and bronchoalveolar lavage (BAL) fluid analysis. In parallel with this research, we have performed comparative gene expression analysis using DNA microarrays in rat lungs after inhalation exposure (4 weeks, 6 hours a day, 5 days a week) to single-wall nanotubes (SWCNTs), multiwall nanotubes (MWCNTs), C60 fullerene and ultrafine nickel oxide particles (Uf-NiO) as reference materials for the purpose of gaining insights into the molecular events following the exposure. In this review, we introduce an outline of the project, and discuss about the significance of comparative gene expression analysis for evaluation of the biological effects of MNs. PMID- 22781014 TI - [Pulmonary toxicity of manufactured nanomaterials]. AB - We introduced the report on the pulmonary toxicity of manufactured nanomaterials as a national project in Japan conducted by the New Energy and Industrial Technology Development Organization (NEDO project). Well-characterized and well dispersed industrial nanomaterials were used in this project. Using multiwall carbon nanotubes (MWCNTs), we conducted intratracheal instillation and inhalation studies. At a low dose (0.2 mg/rat) and a high dose (1 mg/rat) of almost individual MWCNTs, transient and persistent inflammatory responses were induced in the lungs following intratracheal instillation. Well-dispersed MWCNTs at a low concentration (0.37 mg/m3) did not induce pulmonary inflammation. Using single wall carbon nanotubes (SWCNTs), we also conducted both studies. At low (0.2 mg/rat) and high doses (0.4 mg/rat) of well-dispersed SWCNTs, persistent inflammatory responses were induced in the lungs following intratracheal instillation. Well-dispersed MWCNTs at low and high concentrations (0.03 mg/m3 and 0.13 mg/m3, respectively) did not induce pulmonary inflammation. On the basis of these data from mainly inhalation studies, the acceptable exposure concentration of carbon nanotubes is proposed to be 0.03 mg/m3 in Japan. PMID- 22781015 TI - [Activities in daily life and changes in care level among users of Preventive Care Service under Long-Term Care Insurance]. AB - OBJECTIVES: The aim of this study was to investigate the association between social roles (engaged in working outside or house work) or hobbies and changes in care level among users of Preventive Care Service under Long-Term Care Insurance. METHODS: A total of 8,734 Preventive Care Service users were analyzed. The assessment was conducted between February 2007 and December 2008. The improvement, maintenance, and aggravation in care level were defined by changes in care level from the beginning to the end. To assess their activities in daily life, the participants were asked, "Which is the major activity in your daily life? Please select one from the following: working outside, house work, hobbies, watching television, others, or none." We used the multiple logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of the maintenance or improvement in care level according to the category of activity. RESULTS: As compared with subjects who answered none, the multivariate adjusted ORs (95% CI) of the maintenance or improvement in care level were 2.0 (1.4-2.9) for those who answered working outside, 1.5 (1.2-1.8) for those who answered house work, and 1.5 (1.2-1.9) for those who answered hobbies. However, those who answered watching television or others did not show a significant association with the maintenance or improvement in care level. CONCLUSIONS: In this study, compared with subjects who answered none, those who answered that they were engaged in working outside, house work, or hobbies were associated with having significantly higher ORs of the maintenance or improvement in care level. PMID- 22781016 TI - [Examination of influence of adolescent lifestyle on oral hygiene]. AB - OBJECTIVES: In the "biopsychosocial model" propounded by Engel, psychological, biological, and social factors are considered to be interrelated contributors to the causes of illnesses. In this study, we investigated the relationship of oral health in Japanese juveniles with psychological, biological, and social factors. METHODS: The subjects were 227 junior high school students who belonged to a relatively small junior high school in A city, Hiroshima prefecture, Japan. The investigation period was from October 2010 to May 2011. The status of oral health was determined from the results of the caries risk test and periodontal examinations performed using saliva samples. In addition, subjective oral symptoms were determined using questionnaires. Thereafter, the interrelationships among psychological, biological, and individual social (mainly status in the family) factors and preventive methods against oral diseases were discussed. RESULTS: A large number of students were identified to have a high caries risk, and 20% of the students with periodontitis were in need of medical treatment. Oral health status was not influenced equally by the biological, psychological, and social factors. The results suggest that individual social factors influence biological changes through a psychological factor interaction. CONCLUSIONS: The findings suggest that oral disease prevention in juveniles requires an active positive influence of individual social factors, that is, relationships with family members and other individuals, such as medical and educational professionals and individuals involved in juvenile oral health improvement programs. PMID- 22781017 TI - [Relationship between baroreflex function and training effects on altitude training]. AB - OBJECTIVE: Altitude training is frequently used for athletes requiring competitive endurance in an attempt to improve their sea-level performance. However, there has been no study in which the mechanisms by which spontaneous arterial-cardiac baroreflex function changes was examined in responders or nonresponders of altitude training. The purpose of this study was to clarify the different effects of altitude training on baroreflex function between responders and nonresponders. METHODS: Twelve university student cross-country skiers (6 men, 6 women; age, 19+/-1 years) participated in the altitude training in a camp for 3 weeks, which was carried out in accordance with the method of Living High Training Low. Baroreflex function was estimated by transfer function analysis before and after the training. RESULTS: The responders of the training were 3 men and 2 women, and the nonresponders were 3 men and 4 women. In the responders, the transfer function gain in the high-frequency range significantly increased after the training (28.9->46.5 ms/mmHg p=0.021). On the other hand, no significant change in this index was observed in the nonresponders (25.9->21.2 ms/mmHg p=0.405). CONCLUSION: As indicated by the results of transfer function gain in the high-frequency range, the baroreflex function in the responders increased significantly after the altitude training, whereas no significant change was observed in the nonresponders. PMID- 22781018 TI - [Determination of tobacco-specific N'-nitrosamines in mainstream smoke from Japanese cigarettes]. AB - OBJECTIVES: Mainstream smoke from cigarettes contains tobacco-specific N' nitrosamines (TSNAs) listed as Group 1 and 3 carcinogens by the International Agency for Research on Cancer (IARC). Herein, we report on a method of measuring the concentrations of TSNAs in mainstream smoke from the ten top-selling Japanese cigarette brands using an ISO regime by International Organization for Standardization (ISO) and HCI regime of Health Canada. METHODS: Tar in mainstream smoke was collected on a Cambridge filter pad using a smoking machine. The filter pad was immersed in 40 mL of ammonium acetate (pH 6.8) and shaken for 30 min. The extract was then loaded into a C18 column. After washing with 5 mL of 10% methanol and eluting with 5 mL of 70% methanol, the eluate was concentrated to 1 mL for LC-MS/MS analysis. RESULTS: The concentrations of TSNAs in all cigarette brands were higher when determined using the HCI regime than when determined using the ISO regime. Furthermore, the concentrations of TSNAs measured using both the ISO and HCI regimes showed negligible correlation to the tar and nicotine concentrations indicated on package labels. The cigarette samples used in the study were categorized into four classes: ultralow-, low-, medium-, and high-yield brands, which corresponded to 1, 3-6, 8-10, and 14 mg tar/cigarette, respectively. The concentration of TSNAs in ultralow-yield cigarettes was 210 ng/cigarette, as measured using the HCI regime, which was nearly equal to that in high-yield cigarettes (180 ng/cigarette). CONCLUSIONS: Exposure to TSNAs from mainstream smoke from ultralow-yield cigarettes is comparable to that from high yield cigarettes. To properly evaluate the risk of smoking, not only the concentrations of tar and nicotine but also those of other chemicals, including TSNAs, should be printed on package labels. PMID- 22781019 TI - Examining the relation between combat-related concussion, a novel 5-factor model of posttraumatic stress symptoms, and health-related quality of life in Iraq and Afghanistan veterans. AB - OBJECTIVE: This study examined demographic, military, and clinical characteristics associated with combat-related concussion and persistent postconcussive symptoms; and how combat-related concussion and persistent postconcussive symptoms and a novel 5-factor model of posttraumatic stress disorder (PTSD) symptoms are related to physical and mental health-related quality of life in veterans who served in Iraq and Afghanistan. METHOD: 233 veterans recruited from the Veterans Affairs Hawaii Program Registry who served in Iraq and Afghanistan completed a survey in 2010 that assessed combat-related concussion and persistent postconcussive symptoms, PTSD (DSM-IV criteria), alcohol use problems, and physical and mental health-related quality of life. The primary measure was physical and mental health-related quality of life as assessed by the 12-item Short-Form Health Survey, version 2. RESULTS: Veterans who screened positive for combat-related concussion and persistent postconcussive symptoms were more likely than those who did not to report direct combat exposure (chi2 = 15.46, P < .001), living in a rural area (chi2 = 6.86, P < .01), and screening positive for PTSD (chi2 = 37.67, P < .001) and alcohol use problems (chi2 = 11.62, P < .01); 57.3% of veterans who screened positive for combat related concussion and persistent postconcussive symptoms screened positive for PTSD. In bivariate analyses, combat-related concussion and persistent postconcussive symptoms were associated with lower scores on measures of physical and mental health-related quality of life (r = -0.27 to -0.45, P < .001). In multivariate analyses, combat-related concussion and persistent postconcussive symptoms were no longer related to these outcomes, with PTSD-related dysphoric arousal symptoms as the strongest predictor of physical health-related quality of life (beta = -0.55, P < .001) and PTSD-related emotional numbing symptoms (beta = -0.56, P < .001) as the strongest predictor of mental health-related quality of life. CONCLUSIONS: Results of this study suggest that a 5-factor model of PTSD symptoms may provide greater specificity in understanding the relation between combat-related concussion and persistent postconcussive symptoms, PTSD symptoms, and health-related physical and mental quality of life in Iraq/Afghanistan veterans. Psychiatric clinicians should consider this heterogeneity of PTSD symptoms when assessing and treating symptomatic veterans. PMID- 22781020 TI - Effects on cognitive performance of modulating the postprandial blood glucose profile at breakfast. AB - BACKGROUND/OBJECTIVES: Considering the importance of glucose as a brain substrate, the postprandial rate of glucose delivery to the blood could be expected to affect cognitive functions. The purpose was to evaluate to what extent the rate of glucose absorption affected measures of cognitive performance in the postprandial period. In addition, cognitive performance was evaluated in relation to individual glucoregulation. SUBJECTS/METHODS: A white wheat bread (WWB) enriched with guar gum (G-WWB) with the capacity to produce a low but sustained blood glucose net increment was developed. The G-WWB was evaluated in the postprandial period after breakfast with respect to effects on cognitive function (working memory and selective attention (SA)) in 40 healthy adults (49 71 years, body mass index 20-29 kg/m(2)), using a high glycaemic index WWB for comparison in a randomised crossover design. RESULTS: The G-WWB improved outcome in the cognitive tests (SA test) in the later postprandial period (75-225 min) in comparison with the WWB (P<0.01). Subjects with better glucoregulation performed superior in cognitive tests compared with subjects with worse glucoregulation (P<0.05). CONCLUSIONS: Beneficial effects on cognitive performance were observed with the G-WWB in the late postprandial period. The positive effect is suggested to emanate from improved insulin sensitivity, possibly in a combination with an enhanced neural energy supply. The results highlight the importance of carbohydrate foods that induces a low but sustained blood glucose profile in enhancing postprandial cognitive functions. PMID- 22781021 TI - Feto-maternal vitamin D status and infant whole-body bone mineral content in the first weeks of life. AB - BACKGROUND/OBJECTIVES: Compromised vitamin D status is common in pregnancy and may have adverse impacts on fetal development. The purpose of this study was to investigate the association of infant whole-body bone mineral content (WBBMC) at 8-21 days of age with feto-maternal vitamin D status in a multiethnic population in Oakland, California. SUBJECTS/METHODS: This was a cross-sectional study of 120 women and their newborn infants. Maternal and cord blood were collected at delivery. WBBMC was measured by dual-energy X-ray absorptiometry in term-born infants 8-21 days post birth. RESULTS: No significant association was observed between unadjusted or size-adjusted WBBMC and feto-maternal vitamin D status analyzed continuously or categorically. In multivariate modeling, unadjusted WBBMC was predicted by bone area (P<0.0001), weight-for-age (P<0.0001) and weight for-length (P=0.0005) Z-scores, but not by feto-maternal vitamin D status. Anthropometric predictors but not vitamin D remained significant in the multivariate model after adjustment of WBBMC for weight, bone area (bone mineral density) or logarithmically derived exponents of the denominators. CONCLUSIONS: Results of the present study do not support an association between feto-maternal vitamin D status and early infant WBBMC, raw or adjusted for inter-individual differences in size, in a multiethnic population in Northern California. PMID- 22781022 TI - Postpartum diet quality in Australian women following a gestational diabetes pregnancy. AB - BACKGROUND/OBJECTIVES: To describe the diet quality of a national sample of Australian women with a recent history of gestational diabetes mellitus (GDM) and determine factors associated with adherence to national dietary recommendations. SUBJECTS/METHODS: A postpartum lifestyle survey with 1499 Australian women diagnosed with GDM <=3 years previously. Diet quality was measured using the Australian recommended food score (ARFS) and weighted by demographic and diabetes management characteristics. Multinominal logistic regression analysis was used to determine the association between diet quality and demographic characteristics, health seeking behaviours and diabetes-related risk factors. RESULTS: Mean (+/ s.d.) ARFS was 30.9+/-8.1 from a possible maximum score of 74. Subscale component scores demonstrated that the nuts/legumes, grains and fruits were the most poorly scored. Factors associated with being in the highest compared with the lowest ARFS quintile included age (odds ratio (OR) 5-year increase=1.40; 95% (confidence interval) CI:1.16-1.68), tertiary education (OR=2.19; 95% CI:1.52-3.17), speaking only English (OR=1.92; 95% CI:1.19-3.08), being sufficiently physically active (OR=2.11; 95% CI:1.46-3.05), returning for postpartum blood glucose testing (OR=1.75; 95% CI:1.23-2.50) and receiving risk reduction advice from a health professional (OR=1.80; 95% CI:1.24-2.60). CONCLUSIONS: Despite an increased risk of type 2 diabetes, women in this study had an overall poor diet quality as measured by the ARFS. Women with GDM should be targeted for interventions aimed at achieving a postpartum diet consistent with the guidelines for chronic disease prevention. Encouraging women to return for follow-up and providing risk reduction advice may be positive initial steps to improve diet quality, but additional strategies need to be identified. PMID- 22781023 TI - Evidence for augmented oxidative stress in the subjects with type 1 diabetes and their siblings: a possible preventive role for antioxidants. AB - BACKGROUND/OBJECTIVES: Oxidative stress (OS) is thought to be involved in both development of type 1 diabetes (T1D) and its further complications. In this study, certain biomarkers of OS were compared among the subjects with T1D, their non-diabetic siblings and unrelated healthy controls. SUBJECTS/METHODS: Known cases of T1D from both sexes aged 5-25 years were enrolled in a case-control study (n(1)=60). There were two control groups; non-diabetic siblings (n(2)=60) and unrelated apparently healthy subjects (n(3)=60). Anthropometric, dietary and laboratory assessments were done. RESULTS: There was no significant difference in dietary data among the groups. Total antioxidant capacity was significantly lower in T1D than both related and unrelated controls (1.6 +/- 0.05, 1.7 +/- 0.05 and 1.8 +/- 0.06 mmol BSA equivalent/l, respectively, P=0.044). Both T1D subjects and their siblings showed lower glutathione peroxidase (GSH-px) levels (median (interquartile range): 22.2 (28.6), 29.9 (23) and 41.8 (73.6) U/ml, respectively, P=0.006). On the contrary, superoxide dismutase concentrations were significantly higher in T1D group and the siblings than unrelated healthy controls (243 (45.3), 157.8 (176.9) and 27.9 (8.7) U/l, respectively, P<0.001). Serum concentrations of GSH correlated with energy intake in the siblings (r=0.521, P<0.001) and unrelated controls (r=0.268, P=0.042) but not in T1D group. The associations remained significant after controlling for blood glucose (r=0.437, P=0.001 and r=0.420, P=0.011, respectively) in both the groups. CONCLUSION: Augmented OS in the siblings may indicate an increased requirement for antioxidants in genetically diabetes-prone subjects. PMID- 22781025 TI - Lipid accumulation product is a powerful index for recognizing insulin resistance in non-diabetic individuals. AB - BACKGROUND/OBJECTIVES: Lipid accumulation product (LAP) is an index, which combines waist circumference (WC) and triglyceride (TG) reflecting lipid accumulation. The aims of the study were to explore the relationship between LAP and insulin resistance (IR) and to assess whether LAP was superior to WC and body mass index (BMI) in identifying IR. SUBJECTS/METHODS: The study was cross sectional and included 2524 non-diabetic subjects from China. The blood pressure (BP), anthropometric measurements, glucose levels, insulin levels and a fasting lipid profile were measured. BMI, the homeostasis model assessment of IR (HOMA IR) and LAP were calculated. RESULTS: In both sexes, BP, BMI, total cholesterol (TC), non high-density lipoprotein cholesterol (non-HDL-C), HOMA-IR, fasting and postprandial glucose levels increased across LAP quartiles (P<0.001), while HDL cholesterol (HDL-C) levels decreased across LAP quartiles (P<0.001). Pearson's correlation analysis demonstrated that HOMA-IR was correlated with LAP, BMI, WC, TG, HDL-C and non-HDL-C in both sexes (P<0.001). Multivariate analysis demonstrated that LAP had a greater impact on HOMA-IR than BMI and WC. CONCLUSIONS: LAP is closely associated with HOMA-IR and is a powerful index that outperforms BMI and WC in identifying IR in non-diabetic individuals. PMID- 22781027 TI - Costs associated with management of cervical human papillomavirus-related conditions. AB - BACKGROUND: Oncogenic types of human papillomavirus (HPV) have been linked to 99.7% of cervical cancer cases worldwide. METHODS: This retrospective claims based analysis was conducted to assess patterns of use and costs associated with diagnostic and treatment procedures for disease attributed to HPV performed before the introduction of HPV vaccination (January 1, 2001-May 31, 2006). Percentages of commercially insured health plan enrollees who underwent each procedure of interest were calculated for each year. Annual costs (combined patient and health plan-paid amounts) were calculated from qualifying medical claims. Descriptive statistics were used to assess trends in procedure rates and costs. RESULTS: Data for approximately 14.2 million enrollees were obtained. Hysterectomy was the most commonly administered treatment. With the exception of colposcopy with LEEP, all other treatment procedures experienced a decline in rate of use. The most frequently performed diagnostic procedure was colposcopy with endocervical curettage (ECC). With the exception of ECC, rates of diagnostic procedures reached a peak among 20- to 24-year-olds, and followed a downward trend across older groups. Hysterectomy was the most expensive treatment (median $7,383; mean $8,384) per procedure in 2006. CONCLUSION: Results reveal high rates of use and high-associated costs of diagnostic procedures and treatments related to disease attributed to HPV. IMPACT: The data presented may be useful in cost effectiveness analyses and to guide decision makers evaluating how best to optimize prevention strategies. PMID- 22781026 TI - Perceived need to increase physical activity levels among adults at high risk of type 2 diabetes: a cross-sectional analysis within a community-based diabetes prevention project FIN-D2D. AB - BACKGROUND: Increased physical activity is a cornerstone of type 2 diabetes prevention. The perception of a need to change is considered essential in behaviour change processes. However, the existing literature on individuals' perceived need to change health behaviour is limited. In order to improve understanding of diabetes prevention through increased physical activity levels (PAL), we assessed factors associated with perceiving a need to increase PAL among adults at high risk of diabetes. METHODS: Opportunistic screening was used within a primary-care based lifestyle intervention covering 10 149 men and women at high risk of type 2 diabetes. Data were obtained at baseline visits. The explored determinants were demographic, anthropometric/clinical, behavioural and psychosocial characteristics, along with four categories of PAL awareness. Logistic regression was used in the analysis. RESULTS: 74% of men (n = 2 577) and 76% of women (n = 4 551) perceived a need to increase their PAL. The participants most likely to perceive this need were inactive, had a larger waist circumference, rated their PAL as insufficient, and were at the contemplation stage of change. Smoking, elevated blood pressure, dyslipidaemia, and a family history of diabetes were not associated with this perception. The likelihood was also greater among women with less perceived fitness and less education. Demographic factors other than education did not determine participants' perceived need to increase PAL. PAL overestimators were less likely to perceive the need to increase their PAL than realistic inactive participants. CONCLUSIONS: Subjective rather than objective health factors appear to determine the perception of a need to increase PAL among adults at high risk of diabetes. Client perceptions need to be evaluated in health counselling in order to facilitate a change in PAL. Practical descriptions of the associations between metabolic risk factors, PAL, and diabetes are needed in order to make the risk factors concrete for at-risk individuals. PMID- 22781028 TI - Antibody response to Merkel cell polyomavirus associated with incident lymphoma in the Epilymph case-control study in Spain. AB - BACKGROUND: Merkel cell polyomavirus (MCV) has been identified as the cause of Merkel cell carcinoma. The increased incidence of chronic lymphocytic leukemia in Merkel cell cancer cohorts and the lymphotropic properties of the virus suggest a possible viral association with lymphomagenesis. To investigate this potential role, we explored seroreactivity against MCV VP1 capsids within the Epilymph case control study in Spain. METHODS: Serum samples from 468 incident lymphomas, categorized into up to 11 entities, and 522 controls frequency matched by age, sex, and recruitment center were tested for MCV antibodies by enzyme immunoassay using Virus-Like-Particles. Adjusted multinomial logistic regression was used to estimate the OR and 95% confidence interval (CI) associated to MCV seroprevalence. Immunosuppressed subjects were excluded. RESULTS: MCV seroprevalence was 82% in controls and 85% in lymphoma cases. Among 11 lymphoma categories, MCV seropositivity was significantly higher in diffuse large B-cell lymphomas (DLBCL; 96.4%; OR = 6.1, 95%CI = 1.9-19.8), as compared with controls. MCV prevalences were also higher in follicular lymphoma, lymphoplasmacytic lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, and mature T-cell lymphoma but differences did not reach statistical significance. Lower prevalences were observed for multiple myeloma and other B-cell lymphoma. Exclusion of samples collected after start of treatment did not change the results. In a subset analysis, no significant association was observed between BKV and JCV seroprevalence and DLBCL. CONCLUSION: The association observed between serologic evidence of MCV exposure and DLBCL warrants further research. IMPACT: MCV might be involved in the pathway of DLBCL and other lymphomas. PMID- 22781029 TI - Measurement of flowability of lubricated powders by the vibrating tube method. AB - BACKGROUND: The evaluation of lubricity or flowability of pharmaceutical powders is important for consistent production and quality control of drug products. However, there have been only a few studies on quantitative measurements of the properties of lubricated powders. METHOD: Magnesium stearate (MgSt) and sodium stearyl fumarate (SSF) were used as lubricants. Lubricated powders were prepared by adding lubricants to spray-dried lactose under different conditions. To evaluate flowability, the vibrating tube method was used. In this method, the vibration amplitude of the tube is increased at a constant rate, and the mass of the powder discharged from the tube is recorded. Flowability profiles, i.e. the relationships between the mass flow rate and vibration acceleration, were obtained experimentally. To characterize static and dynamic friction properties of powders, critical vibration acceleration required to make powder particles flow and the average mass flow rate were determined. RESULTS: Addition of 0.5% MgSt was sufficient for the reduction of static friction between particles. Blending time of the lubricants had little effect on the average mass flow rate of lubricated powders. On the other hand, addition of SSF resulted in an increase in static friction at the beginning of blending, and after a certain blending time, flowability improved. The combination of MgSt and SSF improved both static and dynamic friction properties irrespective of the blending time. CONCLUSION: The vibrating tube method can be used to evaluate the flowability properties of lubricated powders, and the experimental results provide useful information on the production of pharmaceutical solid dosage forms. PMID- 22781030 TI - Survey of Borreliae in ticks, canines, and white-tailed deer from Arkansas, U.S.A. AB - BACKGROUND: In the Eastern and Upper Midwestern regions of North America, Ixodes scapularis (L.) is the most abundant tick species encountered by humans and the primary vector of B. burgdorferi, whereas in the southeastern region Amblyomma americanum (Say) is the most abundant tick species encountered by humans but cannot transmit B. burgdorferi. Surveys of Borreliae in ticks have been conducted in the southeastern United States and often these surveys identify B. lonestari as the primary Borrelia species, surveys have not included Arkansas ticks, canines, or white-tailed deer and B. lonestari is not considered pathogenic. The objective of this study was to identify Borrelia species within Arkansas by screening ticks (n=2123), canines (n=173), and white-tailed deer (n=228) to determine the identity and locations of Borreliae endemic to Arkansas using PCR amplification of the flagellin (flaB) gene. METHODS: Field collected ticks from canines and from hunter-killed white-tailed were identified to species and life stage. After which, ticks and their hosts were screened for the presence of Borrelia using PCR to amplify the flaB gene. A subset of the positive samples was confirmed with bidirectional sequencing. RESULTS: In total 53 (21.2%) white tailed deer, ten (6%) canines, and 583 (27.5%) Ixodid ticks (252 Ixodes scapularis, 161 A. americanum, 88 Rhipicephalus sanguineus, 50 Amblyomma maculatum, 19 Dermacentor variabilis, and 13 unidentified Amblyomma species) produced a Borrelia flaB amplicon. Of the positive ticks, 324 (22.7%) were collected from canines (151 A. americanum, 78 R. sanguineus, 43 I. scapularis, 26 A. maculatum, 18 D. variabilis, and 8 Amblyomma species) and 259 (37.2%) were collected from white-tailed deer (209 I. scapularis, 24 A. maculatum, 10 A. americanum, 10 R. sanguineus, 1 D. variabilis, and 5 Amblyomma species). None of the larvae were PCR positive. A majority of the flaB amplicons were homologous with B. lonestari sequences: 281 of the 296 sequenced ticks, 3 canines, and 27 deer. Only 22 deer, 7 canines, and 15 tick flaB amplicons (12 I. scapularis, 2 A. maculatum, and 1 Amblyomma species) were homologous with B. burgdorferi sequences. CONCLUSIONS: Data from this study identified multiple Borreliae genotypes in Arkansas ticks, canines and deer including B. burgdorferi and B. lonestari; however, B. lonestari was significantly more prevalent in the tick population than B. burgdorferi. Results from this study suggest that the majority of tick-borne diseases in Arkansas are not B. burgdorferi. PMID- 22781031 TI - Electrical property comparison and charge transmission in p-type double gate and single gate junctionless accumulation transistor fabricated by AFM nanolithography. AB - The junctionless nanowire transistor is a promising alternative for a new generation of nanotransistors. In this letter the atomic force microscopy nanolithography with two wet etching processes was implemented to fabricate simple structures as double gate and single gate junctionless silicon nanowire transistor on low doped p-type silicon-on-insulator wafer. The etching process was developed and optimized in the present work compared to our previous works. The output, transfer characteristics and drain conductance of both structures were compared. The trend for both devices found to be the same but differences in subthreshold swing, 'on/off' ratio, and threshold voltage were observed. The devices are 'on' state when performing as the pinch off devices. The positive gate voltage shows pinch off effect, while the negative gate voltage was unable to make a significant effect on drain current. The charge transmission in devices is also investigated in simple model according to a junctionless transistor principal. PMID- 22781032 TI - [Standardization of diagnosis and treatment is the only way to promote the esophageal cancer treatment and research in China]. PMID- 22781033 TI - [Therapeutic effect of ovarian intra-arterial infusion of GE7-delivery system mediated HSVl-tk/ganciclovir gene therapy in a rat model of malignant ovarian tumor]. AB - OBJECTIVE: To observe the gene expression of herpes simplex virus type 1 thymidine kinase (HSVl-tk) in rat malignant ovarian tumor tissues and the therapeutic effect of ganciclovior (GCV) after intra-arterial infusion of HSVl-tk gene therapy mediated by GE7-delivery system. METHODS: A GE7-polylysine/pCMV-HSV1 tk/polylysine-HA20 4-element complex was constructed. Eighteen rats with DMBA induced ovarian tumor were divided into 3 groups as Atk, ANS and Vtk groups. The 4-element complex GE7-polylysine/pCMV-HSV1-tk/polylysine-HA20 was injected via the ovarian artery into the rats of Atk group, saline buffer was injected in the ANS groups, and the 4-element complex was injected via the tail vein into the rats of Vtk group. All rats received intraperitoneal injection of GCV in a dose of 50 mg/kg daily for 10 days. The rats were sacrificed 3 days after the final dose of GCV, and the tumor weight was measured and tumor growth inhibition rate was calculated. Flow cytometry was used to assess the cell cycle and apoptosis. RESULTS: The tumor weight in the rats of Atk group was (4.77 +/- 2.31) g, significantly lower than that of ANS group [(14.66 +/- 6.26) g, P < 0.01] and Vtk group [(17.53 +/- 7.19) g, P < 0.01]. The tumor growth inhibition rate of the Atk group was 67.5%, while that of Vtk group was -19.6%. The flow cytometry showed that S-phase tumor cells in the Atk group were (54.32 +/- 9.65)%, significantly higher than that in the ANS (27.43 +/- 9.22)% and (30.16 +/- 11.57)% in the Vtk group (both P < 0.01). The tumor cell apoptosis rate in the Atk group was (39.15 +/- 12.16)%, significantly higher than that in the ANS group [(11.86 +/- 5.28)%, P < 0.01] and Vtk group [(14.32 +/- 6.43)%, P < 0.01]. CONCLUSION: HSV1-tk/GCV gene therapy system mediated by GE7 non-viral delivery system via ovarian arterial infusion effectively causes cell cycle arrest at S phase and enhances cell apoptosis, therefore, exerts an inhibitory effect on tumor growth. PMID- 22781034 TI - [Humanized monoclonal antibody TNT-3-mediated truncated tissue factor for the treatment of H22 hepatoma-bearing mice]. AB - OBJECTIVE: To investigate the inhibitory effects of humanized monoclonal antibody 3 (huTNT-3) mediated truncated tissue factor (tTF) on the H(22) hepatoma-bearing mice, and to explore its mechanisms. METHODS: The coagulation activity of the huTNT-3/tTF fusion protein was detected by clotting assay and clotting factor X (FX) activation test in vitro. Mouse hepatoma cell line H(22) cells were inoculated subcutaneously into mice to establish the mouse models of hepatoma. The mice were randomly divided into two groups to be injected once with huTNT 3/tTF fusion protein or tTF protein labeled with rhodamine B isothiocyanate (RBITC), respectively. The localization of huTNT-3/tTF fusion protein in the mouse hepatoma tissue was analyzed by confocal laser scanning microscopy 24 hour after the injection. Fifteen mice were randomly divided into three groups to be injected with the huTNT-3/tTF fusion protein, tTF protein or phosphate buffered saline (PBS) once, respectively. The tumor size was measured every two days to calculate the tumor volume. Ten days after the injection the mice were sacrificed. Samples of the tumor, heart, livers, spleen, lung, kidney and brains of the mice were taken for histopathological examination. RESULTS: Both the huTNT 3/tTF fusion protein and tTF protein effectively promoted blood coagulation. Under the conditions of Ca(2+), the coagulation time in the 1.5, 3, 6 umol/L huTNT-3/tTF groups was (12.90 +/- 0.60) min, (10.39 +/- 0.40) min and(8.15 +/- 0.24) min, respectively, and the coagulation time of the 1.5, 3, 6 umol/L tTF groups was (14.23 +/- 0.46) min, (12.10 +/- 0.49) min and (9.83 +/- 0.52) min, respectively, the difference between the two groups was not significant (F = 0.145, P = 0.705). The huTNT-3/tTF fusion protein was similar to the tTF protein in the ability of activating FX (t = 0.101, P > 0.05). The confocal laser scanning microscopic analysis showed that RBITC-fluorescence labeled huTNT-3/tTF fusion protein was enriched in the hepatoma tissue. The tumor volume of the huTNT 3/tTF fusion protein group was significantly lower than that of the tTF and PBS groups (both P < 0.001), however, there was not significant difference between the tTF and PBS groups (t = -0.616, P > 0.05). The survival time of the huTNT 3/tTF group was (25.5 +/- 2.5) d, significantly longer than that of the PBS group (17.3 +/- 1.9) d and the tTF group (18.6 +/- 1.9) d, (both P < 0.05). CONCLUSION: The huTNT-3/tTF fusion protein retains the coagulation ability and has the capability of targeting to tumor vasculature, and induces thrombosis in the tumor vessels, thus to suppress the growth of hepatoma in the mice. PMID- 22781035 TI - [Hydrogen sulfide stimulates the development of rat glioblastoma]. AB - OBJECTIVE: To address the hypothesis that hydrogen sulfide (H(2)S) is a functionally significant stimulator in the development of glioblastoma (GBM) and explore the mechanism of stimulation. METHODS: Forty adult Sprague-Dawley (SD) rats were given intracerebral injection of rat C6 glioma cell suspension, and an intraperitoneal injection of sodium hydrosulfide (NaHS), an exogenous H(2)S donor. The 40 rats were randomly divided into 4 groups of 10 rats in each: the control group, NaHS group, C6 glioma group (intracerebral implantation of C6 glioma cells) and C6-NaHS group (intracerebral implantation of C6 glioma cells and intraperitoneal injection of NaHS). Food and water were freely available during all phases of the experiment. Physical symptoms were observed and the tumor size was measured. Histological changes were examined by pathology. Immunohistochemical staining was used to analyze the expression of HIF-1alpha and integrated optical density (IOD) was used to determine the tumor microvessel density (MVD). The H(2)S content in the brain was measured. RESULTS: The physical symptoms of tumor-bearing rats became more serious after NaHS injection. The H(2)S level in the C6 glioma group was higher than that in the control group [(35.25 +/- 1.03) nmol/g vs. (29.12 +/- 0.94) nmol/g, P < 0.05], and the highest H(2)S level was found in the C6-NaHS group. The pathological examination showed that the implanted tumors were predominantly spheroid with a distinct border and no capsule could be detected. Neovascular proliferation was also observed. Foci of tumor necrosis, intratumoral hemorrhage, pseudopalisades and tumor cavity were clearly observed. The glioma cells had scant eosinophilic cytoplasm and enlarged hyperchromatic nuclei. All these phenomena were more markedly in the C6-NaHS group compared with that in other three groups. The mean tumor volume was significantly different between the C6 and C6-NaHS rats [(32.0 +/- 6.9) mm(3) vs. (67.8 +/- 11.9) mm(3), P < 0.001]. Immunohistochemical analysis exhibited that the hypoxia-inducible factor-1alpha (HIF-1alpha) and CD34 expression were significantly increased after the intraperitoneal injection of NaHS in the C6 NaHS rats (comparing the IOD between C6-NaHS group and C6 group, HIF-1alpha: 133 962.9 +/- 451.4 vs. 38 569.8 +/- 408.6, P < 0.001; CD34: 73 368.6 +/- 404.8 vs. 14 570.6 +/- 748.7, P < 0.001). Moreover, compared with the C6 group, there were higher MVD in the C6-NaHS group [(41.2 +/- 7.9)/mm(2) vs. (97.0 +/- 10.8)/mm(2), P < 0.001]. CONCLUSIONS: H(2)S serves as a stimulator in the development of rat glioblastoma and exogenous H(2)S strongly promotes the tumor growth. The stimulating mechanisms include the increase of HIF-1alpha expression and neovascular formation. H(2)S may be a significant regulator in the development of tumor. PMID- 22781036 TI - [In vitro interaction of human pancreatic cancer cells and rat dorsal root ganglia: a co-culture model]. AB - OBJECTIVE: To establish an in vitro model of perineural invasion (PNI) with co culture of human pancreatic cancer cells and rat root ganglion, to observe the neurite outgrowth and pancreatic cancer cell proliferation and migration, and to explore the molecular basis of perineural invasion (PNI) of pancreatic cancer. METHODS: Human pancreatic cancer cell line (MIA PaCa-2) and rat dorsal root ganglion (DRG) were co-cultured in Matrigel matrix to generate the PNI model. The neurite outgrowth, pancreatic cancer cell colony formation, neurite-colony contact and retrograde migration were observed under an inverted microscope. The data were analyzed with the Image-Pro Plus 5.0 system. The proliferative index (PI) was measured by immunohistochemical staining with the Ki-67 antibody. In order to determine the absorbance (A) of the pancreatic cancer cells, MTT assay was used. The apoptotic index (AI) was evaluated by flow cytometry. RESULTS: Neurite outgrowth was stimulated in the presence of pancreatic cancer cells. After 72 hours of the co-culture, MIA PaCa colonies co-cultured with DRG exhibited a significantly larger colony area (242.83 +/- 4.92) than that of the control (182.50 +/- 5.39, P < 0.001). In the MIA PaCa-2/DRG co-culture system, the neurites exhibited a trend of growing towards the pancreatic cancer cell colony. However, the pancreatic cancer cells showed a trend of retrogradely migrating to the DRG along the neurite outgrowth, when MIA PaCa-2 colonies touched the DRG. The positive rate of Ki-67 nuclear antigen was significantly higher than in the co-culture group. The PI value was higher in the experimental group (12.80%) than that in the control group (6.81%, P < 0.01). The MTT assay showed that proliferation of the pancreatic cancer cells was more active than that in the control group. Flow cytometry analysis showed that the apoptosis rate of the pancreatic cancer cell was 2.46%, significantly lower than that of the control group (4.89%, P < 0.001). CONCLUSIONS: An in vitro co-culture model of rat dorsal root ganglion and human pancreatic cancer cell line is successfully established in this study. This MIA PaCa-2/DRG co-culture system demonstrates that the neural-pancreatic carcinoma cell interaction is a mutually beneficial process for the growth of neurites and pancreatic carcinoma cells. The pancreatic cancer cells show a trend of migrating to the DRG along the neurite outgrowth. PMID- 22781037 TI - [Isolation and characterization of side population cells in human gastric cancer cell line BGC-823]. AB - OBJECTIVE: Isolate and characterize the side population (SP) cells with potency of stem cells from human gastric carcinoma cell line BGC-823. METHODS: SP and non SP cells were sorted from BGC-823 cells by fluorescence-activated cell sorting (FACS) using Hoechst33342 staining. The tumorigenic ability of the SP cells was assessed by in vivo transplantation into non-obese diabetic/severe combined immunodeficiency mice. RESULTS: SP cells were isolated from BGC-823 cells in a proportion of 0.9% to 2.1% with respect to the whole cell population. The colony formation assay showed that the colony formation rate of the SP cells was significantly higher than that of the non-SP cells (72.56% vs. 49.00%, P < 0.01). The drug sensitivity test showed that the SP cells showed stronger drug resistance to 5-Fu than the non-SP cells. The in vivo transplantation of SP cells in mice showed that the tumor weight was (0.176 +/- 0.034) g, significantly higher than that of non-SP cells (0.045 +/- 0.046) g (P < 0.01). CONCLUSIONS: The results of this study indicate the existence of cancer stem-like SP cells in the human gastric cancer line BGC-823 cells. Further characterization of this SP cell population may provide new insights for diagnosis and treatment of gastric cancer. PMID- 22781038 TI - [Association between HLA-DQA1 gene copy number polymorphisms and susceptibility to gastric cancer]. AB - OBJECTIVE: To explore the association between HLA-DQA1 gene copy number polymorphisms and gastric cancer risk in Chinese population, and the interaction of those genes and environmental factors. METHODS: The genotype of HLA-DQA1 gene copy number polymorphisms was determined in 343 patients with gastric cancer and 330 controls by quantitative polymerase chain reaction. Logistic regression model was used to evaluate the impact of this polymorphism on the risk of developing gastric cancer and the gene-environment interaction. RESULTS: Compared with 0 copy of HLA-DQA1 gene carriers, the 2 copies of HLA-DQA1 gene carriers had a significantly increased risk of gastric cancer (OR = 1.87, 95%CI = 1.15 - 3.06, P = 0.012). Gene-environment interaction of HLA-DQA1 gene copy number polymorphisms and Helicobacter pylori infection significantly increased the risk of gastric cancer in a multiplicative manner, with an OR of 3.89 (95%CI = 1.75 - 8.57, P = 0.001). CONCLUSIONS: HLA-DQA1 gene copy number polymorphism is associated with gastric cancer susceptibility, and there is a multiplicative gene-environment interaction between this polymorphism and Hp infection in the development of gastric cancer. PMID- 22781039 TI - [Distribution of HLA-DRB1 allele polymorphism in the Uyghur women with family history of cervical cancer]. AB - OBJECTIVE: To study the distribution of HLA-DRB1 allele polymorphism in Uyghur women with family history of cervical cancer, and provide theoretical evidence for detection and follow-up of high risk persons for cervical cancer by detection of HLA-DRB1 allele polymorphism. METHODS: The HLA-DRB1 13 alleles were detected in 1000 Uyghur women, all from Hotan Moyu county Karsay village by using polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) assay. RESULTS: The frequencies of HLA-DRB1*15 in women with family history of cervical cancer (17.3%), mother (18.0%) and other relatives except mother (17.0%) who had suffered from cervical cancer were significantly higher than that in the control group (9.7%, all P < 0.05). The frequencies of HLA-DRB1*04 in women with family history (16.8%) and other relatives except mother (20.7%) were significantly higher than that in the control group (12.7%, all P < 0.05). The frequencies of HLA-DRB1*03 in women with family history (2.6%) and other relatives except mother (1.1%) were significantly lower than that in the control group (6.3%, all P < 0.01). The frequencies of HLA-DRB1*12 in women with family history of cervical cancer (2.3%) and mother suffered from cervical cancer (1.5%) were significantly lower than that in the control group (5.7%, all P < 0.05). The frequencies of HLA DRB1*14 in women with family history of cervical cancer (5.4%) and mother who suffered from cervical cancer (3.0%) were significantly lower than that in the control group (8.4%, all P < 0.05). CONCLUSIONS: There are similarity and difference in distribution of HLA-DRB1 allele polymorphisms between the Uyghur women with family history of cervical cancer from Hotan Moyu county and those from southern Xingjiang area. In general, the distribution of HLA-DRB1 allele polymorphism in women with family history of cervical cancer is similar to that reported in abroad. The results of this study support the role of susceptible and protective HLA gene detection in screening high risk persons for this cancer among Uyghur women from cervical cancer high risk areas in Xinjiang. PMID- 22781040 TI - [Expression of epidermal growth factor receptor in salivary adenoid cystic carcinoma and its role in cancer invasion]. AB - OBJECTIVE: To assess the epidermal growth factor receptor (EGFR) status in salivary adenoid cystic carcinoma and explore its role in cancer invasion. METHODS: Fifty-four patients with pathologically confirmed salivary adenoid cystic carcinoma (SACC) were divided into invasion group and non-invasion group. The EGFR expression was determined by immunohistochemstry (SP staining). The relations between the EGFR expression and the SACC clinical pathological characteristics were analyzed. RESULTS: EGFR were mainly expressed in the cell membrane and cytoplasm in the tissue of SACC. The positive rate of EGFR expression in the tumor tissue was 75.9% (41/54), and EGFR was over-expressed in the cytoplasm. The positive rate of EGFR expression in invasion group was higher than that in the non-invasion group (10.0%, P < 0.05). EGFR expression were related with the SACC T stages, histological types, distant metastasis, lymph node metastasis, and nerve invasion (P < 0.05). CONCLUSIONS: A higher expression of EGFR gene in the cytoplasm may have important effect on the progression of invasive carcinoma. Further investigations are required to develop new strategy in the treatment of salivary adenoid cystic carcinoma. PMID- 22781041 TI - [Prognostic analysis of clinicopathological factors in patients after radical resection of esophageal carcinoma]. AB - OBJECTIVE: To explore factors affecting the survival in patients after radical resection of esophageal carcinoma, and to provide a valuable reference for selecting treatment protocol after surgery. METHODS: Clinicopathological data of 618 esophageal cancer patients who underwent radical resection at the Fourth Hospital of Hebei Medical University from May 2002 to June 2006 were collected and reviewed in this study. All patients had no cancer history, did not receive preoperative radiotherapy or chemotherapy, and had Karnofsky performance scores >= 70. Univariate analysis was performed by using log-rank test to determine predictors of survival, and multivariable analysis was performed by a Cox regression model. RESULTS: The overall 1-, 3-, 5-year survival rates were 83.32%, 53.33%, 36.02%, respectively, and the median survival time was 38.33 months. The Cox regression analysis showed that operation mode, intraoperative findings of the extent of tumor invasion, pathological T stage, and the number of metastatic lymph nodes were significant predictors of survival. For patients with lymph node metastasis, the overall 1-, 3-, and 5-year survival rates did not significantly differ between the operation alone group and the postoperative prophylactic radiotherapy group. For patients without lymph node metastasis, the 1-, 3-, and 5 year survival rates were 94.34%, 51.55%, and 34.41%, respectively, in the postoperative radiotherapy group, significantly higher than those in the operation alone group (63.08%, 23.30% and 4.36%; chi(2) = 15.99, P < 0.01). CONCLUSIONS: The independent prognostic factors of esophageal cancer patients after radical resection include the operation mode, intra-operative findings of the extent of tumor invasion, pathological T stage, the number of lymph node metastasis and the number of regions of lymph node metastasis. Postoperative prophylactic radiotherapy is beneficial for esophageal cancer patients with lymph node metastasis. PMID- 22781042 TI - [Clinicopathological features and prognostic analysis of esophageal sarcomatoid carcinoma]. AB - OBJECTIVE: To analyze the clinicopathological characteristics and prognosis of a rare histological type of esophageal cancer-sarcomatoid carcinoma. METHODS: Clinicopathological data of 31 patients with esophageal sarcomatoid carcinoma who underwent surgery in the Department of Thoracic Surgery of Zhejiang Cancer Hospital from Jan 2000 to Dec 2009 were collected and analyzed. The survival analysis was performed using Kaplan-Meier method. RESULTS: All the patients underwent surgery. Of the 31 patients, one received preoperative chemoradiotherapy and postoperative chemotherapy, and 8 received postoperative chemotherapy. All the tumors were located in the middle or lower esophagus. Microscopically, the tumors were composed of both carcinomatous and sarcomatous components, and there was a transition between the two components, but no obvious heterogenous elements such as osteosarcoma, chondrosarcoma or rhabdomyosarcoma were found. In the carcinomatous components, positive expression of CK and EMA was found in all the 31 cases, and positive expression of vimentin in 5 of the 31 cases. In the sarcomatous components, positive expression of CK, EMA and vimentin was found in 29, 28 and 23 cases, respectively. The 1-, 3-, and 5-year survival rates were 80.6%, 55.9% and 33.4%, respectively, and the median survival time was 40 months. CONCLUSIONS: Esophageal sarcomatoid carcinoma is a particular type of esophageal malignancy with unique clinicopathological features. The diversity and complexity of the carcinomatous and sarcomatous components and their potential of transformation and differentiation lead to different prognosis from each other. PMID- 22781043 TI - [Mammographic and pathological features of triple-negative breast cancer]. AB - OBJECTIVE: To retrospectively evaluate the mammographic imaging findings and pathologic changes of the so-called "triple-negative" breast cancer (ER(-)/PR( )/HER-2(-) breast cancer), and to compare them with the ER(+)/PR(+)/HER-2(-) and ER(-)/PR(-)/HER-2(+) breast cancer patients. METHODS: Five hundred cases of breast cancer treated in Cancer Institute and Hospital of Tianjin University from January to June of 2010 were included in this study. There were 112 cases of triple-negative breast cancer, 310 cases of ER(+)/PR(+)/HER-2(-) breast cancer, and 78 cases of ER(-)/PR(-)/HER-2(+) breast cancer. Their pathological and mammographic data were reviewed and analyzed. The pathological and mammographic features of the three groups were compared. RESULTS: Compared with the ER(+)/PR(+)/HER-2(-) breast cancer group, the triple-negative group had a higher histological grade (P < 0.001). Compared with the ER(+)/PR(+)/HER-2(-) and ER( )/PR(-)/HER-2(+) groups, the triple-negative group was more likely to have a tumor mass (simple mass accounted for 58.0%, and tumor mass with calcification accounted for 19.6%). Moreover, compared with the ER(+)/PR(+)/HER-2(-) group (47.1% vs. 9.8%, P = 0.032)and the ER(-)/PR(-)/HER-2(+) group (47.1% vs. 0, P = 0.028), the tumor mass of triple-negative cancer was more likely to have a smooth margin. Triple-negative breast cancer seldom represented as calcification (simple calcification only accounted for 13.4%, and a mass with calcification accounted for 19.6%), and most of them were benign calcification (70.3%), significantly higher than that in the ER(+)/PR(+)/HER-2(-) group (23.1%, P = 0.002) and ER( )/PR(-)/HER-2(+) group (10.2%, P < 0.001). CONCLUSIONS: Different types of breast cancer have different biological characteristics and mammographic features. Analysis of the mammographic features may help us to predict the type of breast cancer and its prognosis, and to select an optimal treatment plan for patients with different types of breast cancer. PMID- 22781044 TI - [Comparison of the results of lymph node dissection via left versus right thoracotomy]. AB - OBJECTIVE: Up to now surgical treatment has been still the most effective treatment for esophageal cancer. However, postoperative lymph node recurrence is still a frequent event and affects long term survival considerably. The aim of this study is to compare the results of lymph node dissection via left vs. right thoracotomies and to verify whether there is any essential difference in lymphadenectomy between these two approaches. METHODS: Five hundred and fifty nine cases with thoracic esophageal cancer were randomly selected from the database of esophageal cancer patients who underwent surgical treatment in our hospital between May 2005 and January 2011, including 282 cases through left thoracotomy and 277 cases through right thoracotomy. This series consisted of 449 males and 110 females with a mean age of 58.8 years (age range: 36 - 78 years). The pathological types were mainly squamous cell carcinoma (548 cases) and other rare types (11 cases). The data were analyzed and compared using Chi-square test. The P-value < 0.05 was considered as statistically significant. The actual 5-year survival rate was calculated based on the recent follow-up data of the patients who underwent surgery at least 5 years ago. RESULTS: The average number of dissected lymph nodes was 23.4 via left versus 24.6 via right thoracotomies. The overall lymph node metastasis rate was 48.9% via left thoracotomy and 53.8% via right thoracotomy, and 34.8% vs. 50.5% in the chest (P < 0.001), 29.1% vs. 17.7% in the abdomen (P = 0.001). The pathologically confirmed lymph node metastasis rate was 45.9%, 44.0% and 34.9% in the upper, middle and lower segments of thoracic esophagus, respectively. The lymph node metastasis rates detected via left and right thoracotomy in the stage T1 cases were 14.7% (5/34) vs. 42.9% (12/28) (P < 0.001), and in the stage T2 cases were 35.4% (17/48) vs. 52.8% (28/53) (P = 0.007); in the station of para-thoracic esophagus were 9.6% vs. 13.4%, in the left upper mediastinum were 2.1% vs. 7.6%, and in the right upper mediastinum were 1.4% vs. 26.0%, respectively. The preliminary actual 5-year survival rate was 38.2% in the cases via left thoracotomy vs. 42.1% in those via right thoracotomy. CONCLUSIONS: The results of this study demonstrate that lymph node dissection is more complete via right thoracotomy than via left thoracotomy, especially for the tracheoesophageal groove and para-recurrent laryngeal nerve nodes, which may eventually improve the survival of patients with esophageal cancer. Therefore, surgical treatment via right thoracotomy by Ivor-Lewis (two incisions) mode or Levis-Tanner (three incisions) mode with two-field or three field complete lymph node dissection may become prevalent in the future. PMID- 22781045 TI - [Comparison of the short-term outcomes of surgical treatment for non-small cell lung cancer via video assisted thoracoscopic surgery and open thoracotomy]. AB - OBJECTIVE: To compare the short-term outcomes of surgical treatment for non-small cell lung cancer (NSCLC) by video-assisted thoracoscopic surgery (VATS) and open thoracotomy (OT). METHODS: Data of 737 consecutive NSCLC patients who underwent surgical treatment for non-small cell lung cancer by video-assisted thoracoscopic surgery and 630 patients who underwent pulmonary resection via open thoracotomy (as controls) in Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and August 2011 were retrospectively reviewed. The risk factors after lobectomy were also analyzed. RESULTS: In the 506 NSCLC patients who received VATS lobectomy, postoperative complications occurred in 13 patients (2.6%) and one patient died of acute respiratory distress syndrome (0.2%). In the 521 patients who received open thoracotomy (OT) lobectomy, postoperative complications occurred in 21 patients (4.0%) and one patient died of pulmonary infection (0.2%). There was no significant difference in the morbidity rate (P > 0.05) and mortality rate (P > 0.05) between the VATS group and OT group. In the 190 patients who received VATS wedge resections, postoperative complications occurred in 3 patients (1.6%). One hundred and nine patients received OT wedge resections. Postoperative complications occurred in 4 patients (3.7%). There were no significant differences for morbidity rate (P = 0.262) between these two groups, and there was no perioperative death in these two groups. Univariate and multivariate analyses demonstrated that age (OR = 1.047, 95%CI: 1.004 - 1.091), history of smoking (OR = 6.374, 95%CI: 2.588 - 15.695) and operation time (OR = 1.418, 95%CI: 1.075 - 1.871) were independent risk factors of postoperative complications. CONCLUSIONS: To compare with the NSCLC patients who should undergo lobectomy or wedge resection via open thoracotomy, a similar short-term outcome can be achieved via VATS approach. PMID- 22781046 TI - [Efficacy and survival status of retuximab-NCE regimen treatment in patients with relapsed or refractory B cell non-Hodgkin's lymphoma]. AB - OBJECTIVE: The aim of this study was to analyze the efficacy and toxicity of RNCE regimen in the treatment of relapsed or refractory B cell non-Hodgkin's lymphoma (NHL). METHODS: From January 2000 to December 2005, 46 patients with relapsed or refractory B cell NHL were treated by RNCE regimen with or without radiotherapy for the involved field. The clinical characteristics, response, toxicity and long term survival results were analyzed retrospectively. RESULTS: A total of 46 patients were eligible. The complete response rate of second-line therapy was 52.17% (24/46), and the overall response rate was 82.61% (38/46). The median follow-up duration in this series was 69 months (range:6 to 102 months). The overall 1, 3, 5-year survival rate was 74.8%, 48.3%, 40.1%, respectively, with a median survival time of 30.2 months (5 to 65 months), and median progression free survival time of 10.9 months (2 to 31 months). The major toxicities were myelosuppression, GI toxicity, fatigue, fever and alopecia. CONCLUSION: Our data show that RNCE regimen treatment is effective and well tolerated in patients with relapsed or refractory B cell non-Hodgkin's lymphoma. PMID- 22781047 TI - [Complications and short-term outcomes of intraoperative electron radiotherapy (IOERT) in patients with periarticular soft-tissue sarcomas of the extremities]. AB - OBJECTIVE: To analyze the complications and short-term outcomes of patients receiving intraoperative electron radiotherapy (IOERT) for locally advanced and recurrent periarticular soft tissue sarcomas of the extremities. METHODS: Twenty one adult patients with locally advanced and/or recurrent periarticular soft tissue sarcomas of the extremities treated with IOERT were included in this study. Among them 14 patients had recurrent diseases after prior operation and 7 patients with locally advanced disease with primary treatment. The total dose of radiation ranged from 11 Gy to 21 Gy of 6 - 12 MeV beta ray given by intraoperative radiotherapy after complete tumor resection with negative margins. Five patients were given external beam radiotherapy (EBRT) with a total dose of 40 - 50 Gy, and 10 patients received chemotherapy. RESULTS: The median follow-up time was 15 months. Five patients (23.8%) had tumor relapse, including one patients with local recurrence, one patient with regional recurrence, two patients with distant metastasis and one patient with local recurrence and distant metastasis. The actuarial local control rate at 1 year was 95.2% (20/21), and at 2 years was 90.5% (19/21). Acute skin toxicity (RTOG) within 3 months after surgery included grade I in 6 patients and grade II in 3 patients. Two year late skin toxicity (RTOG/EORTC) included grade I in 4 patients and grade II in 2 patients. Fibrosis included grade I in 3 patients and grade II in 3 patients. Six patients had joint dysfunction (3 patients with grade I and 3 with grade II) and 6 patients had healing problems. One patient got ipsilateral schiatic neuritis 9 months after IOERT. No adverse events occurred during surgery. CONCLUSIONS: IOERT brings tolerable complications of acute and late toxicities and favorable local control rate. IOERT should be followed by postoperative radiotherapy or increase the intraoperative radiation dose for locally advanced and recurrent sarcomas to get a better local control. Otherwise, distant metastasis is one of the main reasons of treatment failure, so chemotherapy should be added to the treatment regimen. PMID- 22781049 TI - Celebrating Reviewers: your contribution to development of the discipline. PMID- 22781050 TI - An educational partnership in health promotion for pre-registration nurses and further education college students. AB - This paper describes a partnership between a university and a college of further education, whereby first-year nursing students administered health checks to college students. Despite many challenges, the experience was positive for both sets of students and has been mainstreamed. Many lessons were learnt about how best to support nursing students to ensure a good quality experience for both student groups. Data gained from the health checks are also presented, and the programme is compared with the brief community placement that previous nursing students had undertaken at this stage of their training. Theoretical underpinnings for the programme are discussed. PMID- 22781048 TI - [Clinical analysis of the current treatment status of gastric cancer in 636 patients]. AB - OBJECTIVE: To evaluate the current clinical treatment status of gastric cancer in China. METHODS: A retrospective analysis of clinicopathological characteristics of 636 patients with gastric cancer was conducted. Tumor response was evaluated using RECIST version 1.1 criteria. RESULTS: Six hundred and thirty-six patients were included in this retrospective cohort: 479 men and 157 women. The median age was 57 years (14 to 86). The tumor site was: proximal (41.4%), distal (46.4%) or unknown (12.2%). The histology was: adenocarcinoma (85.8%), signet ring cell carcinoma (6.9%), or other and unknown (7.2%). The differentiation of the adenocarcinomas was: well differentiated (31.0%), moderately differentiated (13.4%), poorly differentiated (37.0%), or unknown (18.7%). The pTNM stage was: 0 (0.3%), I (3.6%), II (10.1%), III (36.8%), IV (45.6%), or unknown (3.6%). In 284 patients who underwent radical resection, the ratio of examined ten and/or more lymph nodes was higher in hospitals at or above provincial level than in hospitals at regional level (57.9% vs. 39.6%, P = 0.009). The disease-free survival was longer (21.7 m vs. 14.6 m, P = 0.005), and the overall survival was longer too (52.9 m vs. 33.8 m, P = 0.040). In 205 patients who received adjuvant chemotherapy, the ratio of administered six and/or more cycles chemotherapy was 42.1% vs. 35.2% (P = 0.318), and the disease-free survival was 22.7 m vs. 16.3 m (P = 0.005) between hospitals at or above provincial level and hospitals at regional level. In 387 patients with metastatic or unresectable gastric cancer who received palliative chemotherapy, the overall survival was 11.1 m (95%CI 9.9 12.3 m). Among them, 198 patients received second and/or more line chemotherapy, and the overall survival was longer (12.5 m vs. 7.7 m, P < 0.001). Except a longer progression-free survival (10.2 m, P < 0.05) and a longer overall survival (16.9 m, P < 0.05) were corresponded with the regimen containing trastuzumab, no other significant difference was observed among regimens in first line chemotherapy. CONCLUSION: Chinese doctors working in different level hospitals have a different understanding of the treatment standard of gastric cancer, which resulted in different outcomes. PMID- 22781051 TI - Methodological challenges and approaches to improving response rates in population surveys in areas of extreme deprivation. AB - BACKGROUND: Achieving good response rates to population surveys from hard to reach groups in deprived areas can be challenging. AIM: To explore and compare different approaches to improving response rates in an economically deprived multicultural area. METHOD: Following a lower than anticipated response rate in a pilot study for a postal questionnaire survey of chronic pain (79/653 (12%)), we conducted a second pilot involving a shorter postal survey and separate collection of more detailed information in a waiting room survey. The second postal survey used a shorter questionnaire, telephone data collection from non responders by study team members rather than telephone reminders from practice receptionists, and involved a nested randomised-controlled trial (RCT) of hand addressed versus printed-address envelopes. Both pilots involved subjects randomly selected from the practice registers. RESULTS: The second pilot postal survey using shorter questionnaires yielded considerably more responses (240/642 (37%)). Our RCT showed that hand-addressed envelopes achieved a slightly higher response rate although not large enough to justify its use in our main study. The waiting room survey was successful in collecting more detailed data from lengthy questionnaires. CONCLUSION: A range of methods of questionnaire administration may be required when conducting a survey with a hard to reach group in a deprived and ethnically diverse population. Postal and telephone administration can be used to collect a small amount of data. Face-to-face administration and recruitment can be successful for longer questionnaires. PMID- 22781052 TI - Psychoactive drugs in seven nursing homes. AB - AIMS: We wanted to pinpoint any differences in treatment between participating nursing homes, investigate which drugs are currently prescribed most frequently for long-term patients in nursing homes, estimate prevalence of administration for the following drug groups: neuroleptics, antidepressants, antidementia agents, opioids and the neuroleptics/anti-Parkinson's drug combination, and study comorbidity correlations. We also wanted to study differences in the administration of medications to patients with reduced cognitive functions in relation to those with normal cognition. METHODS: Information about 513 patients was collected from seven nursing homes in the city of Bergen, Norway, during the period March-April 2008. This consisted of copying personal medication records, weighing, recording the previous weight from records, electrocardiography, anamnestic particulars of any stroke suffered, recording if there is cognitive impairment or not and analyzing a standardized set of blood samples. RESULTS: Considerable treatment differences existed between nursing homes, both percentage patients and Defined Daily Dosages. Patients with reduced cognitive functions were prescribed less drugs in general, except neuroleptics. Of all patients, 41.5% were given antidepressants, 24.4% neuroleptics, 22.0% benzodiazepines, 8.0% anticholinesterases and 5.0% memantine. The ratio of traditional to atypical neuroleptics was 122:23. In all, 30.0% of the patients taking neuroleptics were on more than one drug and 35.0% of the patients had opioids by way of regular or as-needed drugs, ratio 14.6%:28.7%. Of 146 patients on neuroleptics, five patients had anti-Parkinson's drugs too. The average use of regular drugs for patient with intact cognition was 7.1 drugs, and for patients with reduced cognitive functions 5.7 drugs. CONCLUSIONS: There are differences in treatment with psychoactive drugs between nursing homes. Patients with reduced cognitive functions receive less cardiovascular drugs than patients with normal cognition. The reason for this still remains unclear. Improvement strategies are needed. The proportion of patients per institution on selected drugs can serve as a feedback parameter in quality systems. PMID- 22781053 TI - Exploring attitudes and practices of General Practice staff towards offers of opportunistic screening for chlamydia: a UK survey. AB - AIM: This study applied a theory-based questionnaire to examine the behaviours and beliefs of all practice staff who may be involved in offering chlamydia screens to young people aged 15-25 years old. We aimed to identify potential influencing factors and examine the organisational constraints, which may be amenable to change. BACKGROUND: The National Chlamydia Screening Programme offers opportunistic screening to men and women between 15 and 25 years old who have ever had sexual intercourse and primary care is the second largest source of screens. In England 15.9% of the target group were screened against a target of 17% in 2008. Interventions to improve the frequency of offers have shown effects with volunteer practices. METHODS: A survey of 85 General Practices was completed by 55 doctors, nurses and receptionists. Interviews were conducted with 12 staff from three practices. FINDINGS: Respondents were unable to identify the national screening target. Only half record if a patient is sexually active. Half the sample had some recollection of the frequency of offers they made, with a mean of 4 per month. These were predominantly in consultations concerning sexual health. Perceived social norms are favourable to screening and respondents have strong perceived control over offering screens, including to those under 16 who are sexually active. Attitudes towards screening were positive but disadvantages and barriers related to increased pressure on practice resources for longer consultations and contact tracing. There were no differences in beliefs and practice behaviours between medical and nursing staff. CONCLUSIONS: Future interventions should be targeted at increasing the range of consultations in which offers are made, demonstrating how to make offers without increasing consultation time, providing more complete records of sexual activity, screens and results, and encouraging audit and review within the practice to promote practice wide approaches to increasing opportunistic screening. PMID- 22781054 TI - An exploration of the perspectives of help-seekers prescribed hearing aids. AB - AIM: This pilot study uses qualitative methods to learn about the psycho-social needs of people who seek help with hearing loss. BACKGROUND: There has been some emphasis in health policy to reduce the number of appointments required between assessment of hearing loss and fitting of hearing aids. This may respond to audiological needs but may not address the psycho-social needs. This study piloted a phenomenological approach to identify the patient's perspective. METHODS: A phenomenological approach was taken to provide description of patient perspectives. Findings Six patients reported that help-seeking was primarily influenced by the need to appease social partners and to improve hearing performance. Hearing aids were not regarded as acceptable treatments. CONCLUSIONS: Service providers need to consider the psycho-social consequences of hearing-aid issue alongside audiological needs. PMID- 22781055 TI - SAPC hot topic--capacity for blue sky research in academic primary care. PMID- 22781056 TI - Definitions of the physical properties of pressure ulcers and characterisation of their regional variance. AB - A pressure ulcer is a localised injury of the skin and underlying tissue that usually develops over a bony prominence. A decrease in the pressure over the bony prominence effectively prevents pressure ulcers; however, no studies have systematically assessed the physical properties of existing pressure ulcers. To characterise pressure ulcers, we established new terminology that clarifies the physical properties of pressure ulcers: wound mobility was defined as movement using the bony prominence as a predefined specific marker, and wound deformity was defined as a change in the three-dimensional shape of the wound. Observational studies using this terminology showed that the distinct physical properties of pressure ulcers depend on the site of development and the wound depth according to the National Pressure Ulcer Advisory Panel criteria. Most grade IV sacrum pressure ulcers exhibited mobility and deformity. Superficial sacrum pressure ulcers below grade II showed only mobility. In contrast, foot pressure ulcers did not exhibit mobility or deformity. We propose a new concept, 'wound physical property', for understanding the unique pathogenesis of pressure ulcers. PMID- 22781057 TI - Nanolithography through mixture of block copolymer micelles. AB - Block copolymer micelle lithography is known for producing ordered and uniform nanostructures. In this report, we have combined different types of block copolymer to produce two interpenetrating lattices of micelle nanoreactors, further extending the capacity of block copolymer micelle lithography. Using polystyrene-block-poly(acrylic acid) and polystyrene-block-poly(4-vinylpyridine), we have generated hexagonally packed hybrid micelles. Metal species can preferentially sequester into poly(acrylic acid) and poly(4-vinylpyridine) cores respectively by immersion of the micelle coated substrates into the metal precursor solution. As a result, metal containing nanoparticle hybrids, such as smaller zinc oxide nanoparticles surrounding larger gold nanoparticles, can be generated. PMID- 22781059 TI - High-flow nasal cannula therapy in do-not-intubate patients with hypoxemic respiratory distress. AB - BACKGROUND: Patients with do-not-intubate (DNI) status and respiratory failure are commonly treated with noninvasive ventilation (NIV). High-flow nasal cannula (HFNC) therapy supplies a high flow of heated and humidified oxygen that may provide an effective alternative to NIV. We assessed the efficacy of HFNC in DNI patients with hypoxemic respiratory distress. METHODS: We identified 50 DNI patients with hypoxemic respiratory distress who were admitted to a medical ICU and who received HFNC. We excluded patients with PaCO2 > 65 mm Hg and pH < 7.28. The primary end point was the need for escalation to NIV, as determined by the primary service. Mean changes in oxygen saturation and breathing frequency before and after HFNC were compared. RESULTS: The subjects included 25 men and 25 women, mean age 73 years (range 27-96 y). Diagnoses (allowing multiple conditions) included pulmonary fibrosis (15), pneumonia (15), COPD (12), cancer (7), hematologic malignancy (7), and congestive heart failure (3). Hospital mortality was 60% (30/50). HFNC was initiated at a mean FIO2 of 0.67 (range 0.30-1.0) and flow of 42.6 L/min (range 30-60 L/min). Mean O2 saturations went from 89.1% to 94.7% (P < .001), and breathing frequency went from 30.6 breaths/min to 24.7 breaths/min (P < .001). Nine of the 50 subjects (18%) escalated to NIV, while 82% were maintained on HFNC. The median duration of HFNC was 30 hours (range 2-144 h). CONCLUSIONS: HFNC can provide adequate oxygenation for many patients with hypoxemic respiratory failure and may be an alternative to NIV for DNI patients. PMID- 22781058 TI - The First Year Inventory: a longitudinal follow-up of 12-month-old to 3-year-old children. AB - The First Year Inventory is a parent-report measure designed to identify 12-month old infants at risk for autism spectrum disorder. First Year Inventory taps behaviors that indicate risk in the developmental domains of sensory-regulatory and social-communication functioning. This longitudinal study is a follow-up of 699 children at 3 years of age from a community sample whose parents completed the First Year Inventory when their children were 12 months old. Parents of all 699 children completed the Social Responsiveness Scale-Preschool version and the Developmental Concerns Questionnaire to determine age 3 developmental outcomes. In addition, children deemed at risk for autism spectrum disorder based on liberal cut points on the First Year Inventory, Social Responsiveness Scale Preschool, and/or Developmental Concerns Questionnaire were invited for in-person diagnostic evaluations. We found 9 children who had a confirmed diagnosis of autism spectrum disorder from the sample of 699. Receiver operating characteristic analyses determined that a two-domain cutoff score yielded optimal classification of children: 31% of those meeting algorithm cutoffs had autism spectrum disorder and 85% had a developmental disability or concern by age 3. These results suggest that the First Year Inventory is a promising tool for identifying 12-month-old infants who are at risk for an eventual diagnosis of autism spectrum disorder. PMID- 22781060 TI - A study of neurobehavioral, clinical psychometric, and P3 changes in vitamin B12 deficiency neurological syndrome. AB - OBJECTIVE: To evaluate cognitive functions and behavioral changes in the patients with vitamin B12 deficiency neurological syndromes (VBDNS) using detailed clinical psychometric and P3 studies and their response to treatment. METHODS: The patients with VBDNS were included and their detailed medical history was recorded. Neurobehavioral and cognitive functions were evaluated by neuropsychiatry inventory (NPI), forward and backward digit span, mini mental state examination (MMSE), Luria's three-step test, trail making test (TMT), motor speed and precision test (MSPT), Benton's visual retention test (BVRT), clock drawing (CD), category fluency, hospital anxiety and depression (HAD) scale, and cognitive evoked potential using oddball paradigm at baseline and 3 and 6 months following treatment. Complete hemogram, serum chemistry, vitamin B12, homocysteine, and craniospinal magnetic resonance imaging (MRI) were done. RESULTS: Thirty-three patients with VBDNS, whose median age was 43 (12-68) years, five (15.2%) of whom were females were included. Twenty-one patients had neurobehavioral/cognitive decline, 26 myelopathy, and 17 neuropathy. MSPT, TMT, CD, and HAD scores improved significantly at 3 months and category naming and MMSE improved at 6 months compared to baseline. The P3 latency also improved significantly at 3 months. The baseline P3 changes correlated with MMSE, Luria's three-step test, and MSPT. Hemoglobin and mean corpuscular volume also correlated with some of the cognitive tests. CONCLUSION: VBDNS results in frontal subcortical neurobehavioral and cognitive abnormalities which may be due to cortical and subcortical dysfunction. The reversibility of these changes is suggestive of metabolic alteration in neuronal or myelin function. PMID- 22781061 TI - Wnt signaling regulates experience-dependent synaptic plasticity in the adult nervous system. PMID- 22781062 TI - Tobacco use and nicotine dependency in a cross-sectional representative sample of 18,018 individuals in Andaman and Nicobar Islands, India. AB - BACKGROUND: Data on prevalence, pattern of tobacco use, proportion of population dependent on nicotine and their determinants are important for developing and implementing tobacco control strategies. The aim of the study was to estimate the prevalence and determinants of tobacco use and nicotine dependency. METHODS: A cross-sectional survey among a representative sample of 18,018 individuals in the age group of >=14 years was conducted in the Union Territory of Andaman and Nicobar Islands during 2007-09. A structured questionnaire, a modified version of an instrument which was used successfully in several multi-country epidemiological studies of the World Health Organisation, was used to survey individual socio-demographic details, known co-morbid conditions, tobacco use and alcohol use. Fagerstrom Test for Nicotine Dependence (FTND) was used to estimate nicotine dependence. RESULTS: The response rate of our survey was 97% (18,018/18,554). Females (n = 8,888) were significantly younger than males (34.3 + 14.6 Vs 36.2 + 15.4 years). The prevalence of current tobacco use in any form was 48.9% (95% CI: 48.2-49.6). Tobacco chewing alone was prevalent in 40.9% (95% CI: 40.1-41.6) of the population. While one tenth of males (9.7%, 95% CI: 9.1 10.4) were nicotine dependent, it was only 3% (95% CI: 2.7-3.4) in females. Three fourth of the tobacco users initiated use of tobacco before reaching 21 years of age. Age, current use of alcohol, poor educational status, marital status, social groups, and co-morbidities were the main determinants of tobacco use and nicotine dependence in the population. CONCLUSION: The high prevalence of tobacco use especially the chewing form of tobacco in the Union Territory of Andaman and Nicobar Islands and the differences in prevalence and pattern of tobacco use and nicotine dependency observed across subgroups warrants implementation of culturally specific tobacco control activities in this population. PMID- 22781063 TI - Grafting of chain-end-functionalized perfluorocyclobutyl (PFCB) aryl ether ionomers onto mesoporous carbon supports. AB - Water-soluble perfluorocyclobutyl (PFCB) aryl ether ionomers bearing sulfonic acid groups in the main chain and phosphonic acid end groups were prepared and used to modify the surfaces of mesoporous carbon materials containing dispersed zirconia nanoparticles. Ionomer surface grafting occurred via phosphonate bonding onto the zirconia particle surfaces. PMID- 22781064 TI - [Analysis of the perinatal outcome and risk factors for pregnancies complicated with chronic renal diseases]. AB - OBJECTIVE: To investigate the perinatal outcome for pregnancies complicated with chronic renal diseases, and the risk factors for the adverse outcome. METHODS: Retrospectively analyze the clinical data of 48 patients with chronic renal diseases complicating pregnancy admitted in Peking University People's Hospital between January 1998 and August 2010, record the pregnancy outcome and explore the risk factors for the poor outcome using multivariate regression analysis. RESULTS: Thirty-eight patients had known chronic renal disease before conception, and ten were diagnosed during pregnancy. Seven patients (15%, 7/48) presented with obvious renal impairment [serum creatinine (sCr) >= 125 umol/L] prepregnancy, and nine (19%, 9/48) were recorded with chronic hypertension. Thirty-three patients received regular prenatal care. Twenty-one cases (44%, 21/48) developed preeclampsia. During the gestation, normal renal function (defined as sCr < 71 umol/L) was seen in nineteen cases (40%, 19/48), mild dysfunction (sCr ranged 71 - 132 umol/L) in twenty (42%, 20/48) and moderate to severe dysfunction (sCr >= 132 umol/L) in nine cases (19%, 9/48). Twenty patients had negative or mild proteinuria (24 hour urine protein < 2000 mg), 19 had moderate (24 hour urine protein ranged 2000 - 5000 mg) and nine had severe proteinuria (24 hour urine protein >= 5000 mg). The gestational age at delivery ranged from 24 to 41 weeks and the neonatal birth weight ranged from 890 to 4150 g. A total of twenty patients (42%, 20/48) suffered adverse perinatal outcome, including one case with late spontaneous abortion, fifteen with preterm delivery, eleven with small for gestational age, two with neonatal respiratory distress syndrome and four with perinatal death. Declined maternal renal function was seen in eight patients, and two patients progressed toward the end-stage renal failure (the stage of uremia). Multivariate regression analysis identified that preeclampsia (OR = 24.72, P = 0.002) and the degree of proteinuria (OR = 4.24, P = 0.032) were the independent risk factors for the adverse perinatal outcome. CONCLUSIONS: Pregnancies complicated with chronic renal diseases have significantly high incidence of preeclampsia and adverse perinatal outcome. Preeclampsia and the degree of proteinuria are perhaps the independent risk factors for the adverse outcome. PMID- 22781065 TI - [Diagnostic value of radom spot albuminuria to creatinine ratio in women with preeclampsia]. AB - OBJECTIVE: To investigate the correlation between spot albuminuria to creatinine ratio (ACR) and 24 h urinary protein excretion in women with preeclampsia and determine the optimal cut-off values of spot ACR in mild preeclampsia and severe preeclampsia. METHODS: Twenty-eight women with mild preeclampsia and 22 with severe preeclampsia at Nanfang Hospital, Southern Medical University between October 2010 and June 2011 were recruited. Maternal serum cystatin, uric acid, urea nitrogen, creatinine and albumin levels were collected and analyzed. Twenty four hours urinary protein excretion was measured with immunoturbidimetric assay and ACR with automatic analyzer DCA2000. The correlation between ACR and 24 hours urinary protein excretion was explored. And the optimal cut-off values of the spot ACR for mild and severe preeclampsia were determined with receiver operating characteristic curve. RESULTS: (1) Maternal serum biochemical parameters: uric acid levels in mild and severe preeclampsia were (359 +/- 114) umol/L and (450 +/ 132) umol/L, while cystatin levels were (1.3 +/- 0.3) mg/L and (1.6 +/- 0.5) mg/L respectively. The differences were statistically significant (P < 0.05). Serum urea nitrogen, creatinine and albumin in mild preeclampsia were (3.6 +/- 1.6) mmol/L, (52 +/- 38) umol/L and (33 +/- 3) g/L, while in severe preeclampsia were (6.2 +/- 3.1) mmol/L, (78 +/- 59) umol/L and (29 +/- 6) g/L respectively. There were no statistical significant differences (P > 0.05). (2) Twenty-four hours urinary protein excretion and ACR: 24 hours urinary protein levels in mild and severe preeclampsia was (700 +/- 160) mg and (4800 +/- 2200) mg (P < 0.05). ACR in mild and severe preeclampsia was (72.7 +/- 12.4) mg/mmol and (401 +/- 245) mg/mmol respectively (P < 0.05). (3) There was a strong correlation between the spot ACR and 24 hours urine protein excretion (r = 0.938; P < 0.05). (4) The optimal spot ACR cut-off point for the diagnosis of preeclampsia: the optimal spot ACR cut-off point was 22.8 mg/mmol for 300 mg/24 hours of protein excretion in mild preeclampsia, the area under curve was 0.956, with a sensitivity, specificity of 82.4%, 99.4% respectively. And the optimal spot ACR cut-off point was 155.6 mol for 2000 mg/24 hours of protein excretion in severe preeclampsia, the area under curve was 0.956, with a sensitivity, specificity of 88.6%, 91.3% respectively. CONCLUSIONS: Compared with 24 hours urinary protein excretion, the spot ACR may be a simple, convenient and accurate indicator of early diagnosis of preeclampsia. Spot ACR may be used as a replacement for 24 hours urine protein excretion in assessment of preeclampsia. The optimal spot ACR cut off points were 22.8 mg/mmol for mild preeclampsia and 155.6 mg/mmol for severe preeclampsia. PMID- 22781066 TI - [Study on the changes of cardiac reserve function during normal vaginal delivery]. AB - OBJECTIVE: To investigate the trend of cardiac reserve function during the normal labor. METHODS: Sixty-three cases were chosen randomly from hospitalized maternal women in the First Affiliated Hospital of Chongqing Medical University from 2010 June to December (six months). The digital technique of heart sound signal processing was used to analyze cardiac reserve function parameters including the heart rate (HR), the ratio of the amplitude of the first heart sound to the second heart sound (S1/S2) and the ratio of diastolic to systolic duration (D/S) of pregnant women. RESULTS: (1) Comparisons of cardiac reserve function between uterine contractions and relaxations during labor: 1) Latent phase of labor (cervix dilation < 3 cm):HR was (87.3 +/- 14.0) beats/min in uterine contractions and (82.8 +/- 12.5) beats/min in uterine relaxations, the ratio of D/S was 1.14 +/- 0.27 in uterine contractions and 1.21 +/- 0.22 in uterine relaxations, the comparisons of the above two were statistically significant, P < 0.05; But the ratio of S1/S2 was 2.19 +/- 0.82 in uterine contractions and 2.28 +/- 0.81 in uterine relaxations, the comparison was not statistically significant, P > 0.05. 2) During early active stage of labor (cervix dilation 3 - 6 cm):HR was (89.3 +/- 15.4) beats/min in uterine contractions and (83.1 +/- 13.5) beats/min in uterine relaxations, the ratio of D/S was 1.09 +/- 0.30 in uterine contractions and 1.20 +/- 0.27 in uterine relaxations, the comparisons of the above two were statistically significant, (P < 0.05); But the ratio of S1/S2 was 2.42 +/- 1.08 in uterine contractions and 2.29 +/- 0.83 in uterine relaxations, the comparison was not statistically significant (P > 0.05); 3) During late active stage of labor (cervix dilation 6 - 10 cm), HR was (95.4 +/- 18.7) beats/min in uterine contractions and (86.2 +/- 15.6) beats/min in uterine relaxations, the ratio of D/S was 1.01 +/- 0.25 in uterine contractions and 1.18 +/- 0.25 in uterine relaxations, the comparisons of the above two were statistically significant, (P < 0.05); But the ratio of S1/S2 was 2.61 +/- 1.26 in uterine contractions and 2.67 +/- 1.19 in uterine relaxations, the comparison was not statistically significant (P > 0.05). 4) The second stage of labor (cervical dilation >= 10 cm):HR was (109.4 +/- 19.7) beats/min in uterine contractions and (93.5 +/- 16.7) beats/min in uterine relaxations, the ratio of D/S was 0.89 +/- 0.23 in uterine contractions and 1.14 +/- 0.26 in uterine relaxations, the ratio of S1/S2 was 3.66 +/- 1.37 in uterine contractions and (2.81 +/- 1.07) in uterine relaxations, the comparisons of all were statistically significant (P < 0.05). (2) Comparison of cardiac reserve function in uterine relaxations of each stage of labor: 1) Maternal heart rate gradually increased from latent stage of labor to the second stage of labor, and decreased postpartum, the comparison was statistically significant (P < 0.05); 2) The ratio of S1/S2 of maternal gradually increased from latent stage of labor to the second stage of labor, and decreased postpartum, the comparison was statistically significant (P < 0.05); 3) The ratio of D/S gradually decreased from latency to the second stage of labor, and increased postpartum, the comparison was statistically significant (P < 0.05). (3) Comparison of cardiac reserve function in uterine contractions of each stage of labor: 1) Maternal heart rate gradually decreased from latent stage of labor to the second stage of labor, the comparison was statistically significant (P < 0.05); 2) The ratio of S1/S2 of maternal gradually increased from latent stage of labor to the second stage of labor, the comparison was statistically significant (P < 0.05); 3) The ratio of D/S gradually decreased from latency to the second stage of labor, the comparison was statistically significant (P < 0.05). CONCLUSIONS: The maternal cardiac reserve function decreased in uterine contractions than relaxation during labor; With the progress of labor, the maternal cardiac reserve function declined, especially in the second stage of labor, and recovered in postpartum stage. PMID- 22781067 TI - [Clinical study of 12 cases with obstetric mirror syndrome]. AB - OBJECTIVE: To discuss the clinical features, management, pregnancy outcome and prognosis of obstetric mirror syndrome. METHODS: The clinical data of 12 cases with obstetric mirror syndrome at Shenzhen Maternity and Child Healthcare Hospital from April 2008 to December 2010 were collected to retrospectively analyze the clinical features, management, pregnancy outcome and prognosis. RESULTS: (1) ETIOLOGY: 12 cases with obstetric mirror syndrome included 9 cases of Bart's hydrops fetalis, 2 cases with fetal complicated congenital cardiac anomalies, and 1 case of unknown etiology. (2) Gestational age at diagnosis and at delivery: gestational age at diagnosis ranged from 28 to 36 weeks [mean (31.5 +/- 4.7) weeks], and gestational age at delivery ranged from 28(+3) to 38 weeks [mean (32.9 +/- 2.9) weeks]. There were no significant differences between the gestational age at diagnosis and at delivery in consistence with severe preeclampsia group and mild preeclampsia group [(31.8 +/- 2.3) weeks vs. (30.9 +/ 7.2) weeks, (32.5 +/- 2.3) weeks vs. (33.5 +/- 3.9) weeks, P > 0.05]. (3) The patients with obstetric mirror syndrome can present a preeclampsia-like syndrome: maternal extremity edema in 12 cases, headache and visual disturbance in 1 case, proteinuria in 11 cases, elevated blood pressure in 5 cases, elevated uric acid in 9 cases, hypoproteinemia in 12 cases, elevated creatinine in 3 case, elevated liver enzyme in 1 case, thrombocytopenia in 2 cases. The major complications included 1 case of HELLP syndrome, acute pulmonary edema, placental abruption, amnionic fluid embolism, DIC respectively, 3 cases of acute kidney failure and 6 cases of postpartum hemorrhage. (4) Sonographic findings: 1) Hydrops fetalis: fetal ultrasound revealed pleural fluid, fetal ascites, skin edema, scalp edema, encephalocolele enlargement, hydropericardium and increased cardio-chest ratio. 2) Placenta megaly: the placental pathological examination revealed edematous and large in 12 cases. Placental thickness was beyond 4 cm in all cases [(6.3 +/- 1.9) cm]. 3) Hydramnios: hydramnios could be found in 11 cases [amniotic fluid index (19.7 +/- 3.1) cm]. (5) Postnatal conditions:all blood pressure and laboratory findings including urine protein normalized within 5 to 7 days after delivery. (6) Pregnancy outcome:all 12 patients survived, however the perinatal mortality rate was 100%. Two of 12 cases with mirror syndrome underwent cesarean section, and 10 were vaginal delivery, of which 1 need uterine artery embolisom due to postpartum hemorrhage. CONCLUSIONS: Obstetric mirror syndrome seems to simulate preeclampsia although there are distinguishing features, such as hemodilution, placental edema, and polyhydramnios. When the specific cause of obstetric mirror syndrome can not be identified and corrected, the decision for delivery should be made as soon as possibly. PMID- 22781068 TI - [Vascular endothelial growth factor gene polymorphisms and the risk of endometriosis: a systematic review]. AB - OBJECTIVE: To analyze the potential association between the single nucleotide polymorphisms (SNP) of the vascular endothelial growth factor (VEGF) gene with the risk of endometriosis by meta-analysis. METHODS: Published case-control studies about the influence of VEGF polymorphisms on endometriosis were searched and screened in Medline, the Cochrane library, China National Knowledge Internet (CNKI), Chinese Biological Medicine Disk (CBM), data base of Wanfang and Foreign Medical Journal Full-Text Service (FMJS). RevMan 5.0 software was used for meta analysis. RESULTS: Finally, there were 9 literatures including 1610 endometrisis patients and 1643 controls cases, which were eligible for the criteria to investigating the VEGF SNP about -460C/T, +405C/G and +936C/T. The results of meta-analysis showed that there was no evidence for association between endometriosis and the VEGF -460C/T SNP in the genotype or allele frequencies distribution (P > 0.05). Significant differences were found between the frequencies distribution of VEGF +405CC genotype (P = 0.009, OR = 1.45, 95%CI: 1.10 - 1.91) and +405C allele (P = 0.020, OR = 1.19, 95%CI: 1.03 - 1.38), also between the +936CC genotype (P = 0.050, OR = 0.81, 95%CI: 0.66 - 1.00) and +936T allele (P = 0.040, OR = 1.20, 95%CI: 1.01 - 1.43). CONCLUSIONS: The VEGF +405C/G and +936C/T SNP may be associated with the risk of endometriosis. Women carrying the +405C or the +936T allele could significantly increase the risk of developing endometriosis. PMID- 22781069 TI - [Analysis of cervical HPV infection in HIV positive Chinese women]. AB - OBJECTIVE: To investigate prevalence HPV infections in cervix among HIV-infected Chinese women. METHODS: From September 2009 to May 2011, 293 women with positive HIV underwent cervical cancer screening as study group matched with 200 women with negative HIV as control group. Questionnaires including demographic information and HIV associated information were collected, Pap smear and 23 subtype of HPV were performed in those women. The women with positive HPV were followed up per 6 months, and the period of following up were more than 12 months. Binary logistic analysis was used for high risk factors of HPV persistent infection. RESULTS: Prevalent HPV infection was 44.4% (130/293) in study group and 20.0% (40/200) in control group, respectively, which reached statistical difference (P < 0.05). The most common genotype of HPV was HPV 16, which prevalence was 13.7% (40/293) in study group and 7.0% (14/200) in control group. The other HPV subtype prevalence was HPV-58, HPV-52, HPV-43 and HPV-18, which was 9.2% (27/293), 8.2% (24/293), 8.2% (24/293), 6.8% (20/293) in study group and 3.0% (6/200), 2.5% (5/200), 1.5% (3/200), 2.5% (5/200) in control group. At time point of 12 months following up, the persistent prevalence of HPV was 47.5% (48/101) in study group and 21.1% (8/38) in control group, which reached statistical difference (P < 0.05). Multiple HPV infections (OR = 6.4, 95%CI: 1.6 25.6), abnormal cytology (OR = 18.1, 95%CI: 4.5 - 76.9) and lower CD(4) T cell count (compared with CD(4) > 3.5 * 10(8)/L, if 2.0 * 10(8) <= CD(4) <= 3.5 * 10(8), OR = 8.1, 95%CI: 1.3 - 56.3; if CD(4) < 2.0 * 10(8)/L, OR = 9.1, 95%CI: 1.8 - 46.9) were independently associated with HPV persistence among HIV-positive subjects. CONCLUSIONS: Prevalence and persistence of HPV infections were more common among HIV-positive Chinese women than those in HIV-negative Chinese women. Improving immune function, decreasing multiple HPV infections, treating abnormal cervical cytology could decrease prevalence of HPV infection. PMID- 22781070 TI - [Analysis of 25 cases of brain metastasis from gynecological cancers]. AB - OBJECTIVE: To discuss the clinical characteristics, treatment and prognostic factors of brain metastasis from gynecological cancers. METHODS: Clinical records of 25 brain metastasis patients from gynecological cancers admitted from January 1999 to January 2009 were reviewed retrospectively. The curative effects of different treatments were compared. The prognostic factors were determined using the Cox regression model. RESULTS: There were 14 cases ovarian malignant tumor, 6 cases cervical carcinoma and 5 cases uterine malignant tumor. Seven cases (28%, 7/25) had solitary metastatic lesion in the brain. Extracranial metastases were detected in 18 cases (72%, 18/25). Five patients only received one kind of treatment, and the mean survival time was 4.0 months (0.5 to 9.5 months). Sixteen patients received combined treatment, 3 of them received combined treatment including surgery, and the mean survival time was 8.4 months (4.1 to 13.4 months); 13 of them received chemotherapy and radiotherapy, and the mean survival time was 14.2 months (4.3 to 58.1 months). Four patients received only palliative supportive care, and the survival time was only 0.1 to 1.0 month. The Cox regression model showed that Karnofsky performance status scale, with or without extracranial metastases and the treatment method were the independent prognostic factors of brain metastasis from gynecological cancers (P < 0.05). CONCLUSION: The incidence of brain metastasis from gynecological cancers is low and the prognosis is very poor. Combined treatments may get better effects. PMID- 22781071 TI - [Promoter methylation of DAPK1, RAR-beta and MGMT in exfoliated cervical cytology and its clinical application]. AB - OBJECTIVE: To assess the correlation of promoter methylation of DAPK1, RAR-beta and MGMT with cervical lesions from cytology to histology, and to reveal the clinical value of DNA methylation in diagnosis of cervical intraepithelial neoplasia (CIN). METHODS: A total of 103 random-selected cervical samples were collected from residual liquid-based cytology specimens after clinical use in cytopathological diagnosis in outpatient clinic of obstetrics and gynecology, Peking Union Medical Collage Hospital from March 2010 to October 2010. Informed consent was obtained from each woman before the initiation of the study. The methylation sensitive-high resolution melt (MS-HRM) assay was used to evaluate promoter methylation of three genes (DAPK1, RAR-beta and MGMT) in 103 biopsy confirmed liquid-based cervical cytology samples. Methylation levels and high risk HPV DNA loading (HCII values) were analyzed in relation to both cytological and histological diagnosis. RESULTS: The methylation level of all three genes showed significant difference among the different cytological groups (P = 0.000, 0.011 and 0.002, respectively). The methylation level of DAPK1 and RAR-beta showed significant difference among the different histological groups (P = 0.000 and 0.021), while there was no significant difference for MGMT. DAPK1 methylation levels was 1.47% in the CINII/high-grade precancerous lesions group, and 20.98% in the normal/CINI groups (P = 0.000), but there was no significant difference between CINII/high-grade precancerous lesions and normal/CINI groups for RAR-beta and MGMT. The combination of DAPK1/HR-HPV loading showed a sensitivity of 0.825 and an area under the receiver operating characteristic curve (ROC) curve (AUC) of 0.695 as diagnostic methods for detecting CINII/high-grade precancerous lesions. CONCLUSIONS: DNA methylation such as DAPK1 and RAR-beta, in combination with HR-HPV detection, may serve as biomarkers to detect CINII/high-grade precancerous lesions. Detection of methylated DNA from liquid-based cervical cytology specimens is technically feasible with the MS-HRM assay. PMID- 22781073 TI - [Inhibitory effects on Candida albicans of vagina cells transferred with antimicrobial peptide LL-37 and human defensin 5 recombinant plasmids]. AB - OBJECTIVE: To evaluate the inhibitory effects on Candida albicans of vagina cells transferred with antimicrobial peptide LL-37 and human defensin 5 (HD5) recombinant plasmids and observe secretion of IL-8. METHODS: (1) The epithelial cells from female vagina were culture primarily. The pcDNA3.1(+)/HD5-EGFP and pcDNA3.1(+)/LL-37-EGFP eukaryotic recombinant plasmids were separately or jointly transferred into the fourth generation of vaginal epithelial cells. Two test groups were defined: one test group was no Candida albicans group including four subgroups which were untransferred group, HD5 group transferred with pcDNA3.1(+)/HD5-EGFP, LL-37 group transferred with pcDNA3.1(+)/LL-37-EGFP, combining transferring group transferred with pcDNA3.1(+)/HD5-EGFP and pcDNA3.1(+)/LL-37-EGFP; the other test group was with Candida albicans group which the Candida albicans were coincubated with the four subgroups described above. (2) For examination of cytokines and chemokines, at 6, 12, 24 and 48 hours, the supernatant of every group was collected. ELISA was applied to detect the levels of LL-37, HD5 and IL-8. At each time point, the growth inhibition of Candida albicans was calculated by glucose consumption testing. RESULTS: (1) The max level of LL-37, HD5 and IL-8 reached max level after being transferred for 24 hours, then showed decreasing trend. The secretion of LL-37, HD5 and IL-8 was significant higher in combining transferring group in Candida albicans group than other groups, and the secretion level of LL-37, HD5 and IL-8 was (100.16 +/- 0.81) ng/ml, (58.50 +/- 2.08) ug/ml and (101.03 +/- 1.59) pg/ml (P < 0.01). (2) In different time point, the absorbance of each subgroup without Candida albicans declined slowly, and there were no statistically significant difference (P > 0.05), as while as in LL-37 subgroup and HD5 subgroup with Candida albicans. In group with Candida albicans, the absorbance of combining transferring subgroup were 3.210 +/- 0.010, 3.150 +/- 0.030, 3.099 +/- 0.030 and 2.970 +/- 0.040 at 6, 12, 24 and 48 hours, respectively, which was significantly higher than those in the other cells (P < 0.01), and the declined trend was the slowest. CONCLUSIONS: The antifungal ability of vaginal epithelial cell became stronger after being transferred with LL-37 and HD5 recombinant plasmids. LL-37 and HD5 could also possess immunomodulatory activity and induce chemokine IL-8 production. PMID- 22781072 TI - [Clinicalpathological characteristics of Lynch syndrome related epithelial ovarian cancer]. AB - OBJECTIVE: To explore the clinical pathological characteristics of Lynch syndrome associated ovarian cancer. METHODS: Totally 260 cases ovarian cancer patients were admitted to Tianjin Medical University General Hospital during Jan. 2004 and Jan. 2011, among which 10 patients (LS group) belonged to Lynch syndrome associated ovarian cancer according to Amsterdam II criteria. One hundred ovarian cancer patients without any family cancer history were enrolled randomizely as control group (sporadic group). RESULTS: Lynch syndrome associated ovarian cancer accounted for 3.8% (10/260), the incidence rate of ovarian cancer for female family members of Lynch syndrome was 8.7% (10/115). Mean age at time of diagnosis in LS group was (46 +/- 7) years, significantly earlier than that in sporadic group [(56 +/- 11) years, P < 0.05]. There was no statistical difference between two groups in histological type or International Federation of Gynecology and Obstetrics (FIGO) stage (P > 0.05). Most of the tissue differentiation in LS group were well or moderate differentiated, there was statistical difference between the two groups (9/10 vs. 55%, P < 0.05). The 3-year and 5-year survival rate in LS group were 87.5% and 52.5% respectively, compared with 55.4%and 22.7% in sporadic group (all P < 0.05). CONCLUSION: Compared with sporadic ovarian cancer, Lynch syndrome associated ovarian cancer is more likely present as the clinical pathological characteristics of early age of onset, serous adenocarcinoma, lower grade and better prognosis. PMID- 22781074 TI - [Impact of calcium channel antagonists for estrogen action on the endometrial carcinoma HEC-1A cells]. AB - OBJECTIVE: To study the effects of nifedipine and mibefradil on the cell proliferation, apoptosis, migration on the HEC-1A in vitro and also study the mRNA and protein expression levels of the calcium channel alpha1D (Cav1.3) and calcium channel alpha1G (Cav3.1) to discuss the effects of the calcium antagonists on the mechanisms of the endometrial carcinoma. METHODS: (1) Add 10 umol/L nifedipine and mibefradil at 15 minutes before adding 10 umol/L 17beta estradiol (17beta-E(2)) and 100 umol/L b-estradiol-6-(O-carboxymethyl)oxime (E(2) BSA) to the HEC-1A in different time including 0, 5, 15, 30, 60, 120 minutes. Then the changes of mRNA and protein were detected by reverse transcripiton (RT) PCR and western-blot. (2) Add 1.25, 2.5, 5, 10, 20, 40, 80, 100 umol/L nifedipine and mibefradil to the HEC-1A at 24, 48, 96 hours to detect the cell proliferation by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method. (3) Add 10 umol/L nifedipine and mibefradil to the HEC-1A, then detect the apoptosis at 0 minute, 30 minutes, 1 hour, 6 hours, 24 hours and migration in vitro at 36 hours with transwell methods. RESULTS: (1) After the pretreated effect of the nifedipine before 17beta-E(2), the mRNA express of Cav1.3 genes was lowest at 15 minutes, and returned to the control level after 30 minutes. The protein level didn't change very much in 30 minutes, but rose after 60 minutes. The Cav3.1 genes mRNA express was lowest at 5 minutes, rose at 30 minutes and returned to the 0 minute level gradually. (2) After the pretreated effect of the nifedipine before E(2)-BSA, the Cav1.3 genes mRNA was lowest at 5 minutes and returned at 15 minutes. The protein level rose gradually in 15 minutes but reduced after 15 minutes. The Cav3.1 mRNA and protein level were reduced at every time point. (3) After the pretreated effect of the mibefradil before 17beta-E(2), there was no change of mRNA expression of Cav1.3 genes. The protein level rose at 15 and 60 minutes, there was no change in any other time. The Cav3.1 genes mRNA were gradually reduced and the protein level rose at 15 minutes, and there was no change in any other times. (4) After the pretreated effect of the mibefradil before E(2)-BSA, the mRNA and protein of Cav1.3 levels were reduced after 15 minutes. There was no mRNA expression of Cav3.1, while the protein level was lowest at 15 minutes. (5) Nifedipine and mibefradil affected HEC-1A proliferation depended on the different concentration and interval time points. There was significant difference than those in control group (P < 0.05). (6) There were statistical differences in apoptosis rate after adding nifedipine (P < 0.05), while rose at mibefradil treated the same time (24 hours: 8.41 +/- 0.07, 0 minute: 3.74 +/- 0.18; P < 0.05). (7) The numbers of stained cells after both nifedipine and mibefradil treated reduced more than control group. CONCLUSIONS: (1) Nifedipine and mibefradil could inhibit both the effect of the estrogen on the L-type and T-type calcium channel in short time, meanwhile the mibefradil effects last long time. (2) The inhibited effect of the mibefradil on the proliferation, apoptosis and migration of HEC-1A cells in vitro is more significant than that by nifedidipine. PMID- 22781076 TI - Polycystic ovary syndrome in adolescents. AB - PURPOSE OF REVIEW: To highlight the new information in the field of polycystic ovary syndrome (PCOS) in adolescents and how it may pertain to current practice. RECENT FINDINGS: The diagnosis of adolescent PCOS remains controversial, and experts continue to debate the appropriate criteria to be used. There is growing support for using Rotterdam criteria, but requiring the presence of all three criteria (oligoovulation or anovulation, hyperandrogenism and polycystic ovaries on pelvic ultrasonography), as the standard 'two of three' criteria may overdiagnose PCOS in adolescents. As adolescent PCOS is better understood, a high rate of metabolic syndrome and sleep disorders is appreciated, which likely has implications on long-term health. The mainstay of PCOS treatment in adolescents should be lifestyle modification (diet, exercise and behavioral changes), and evidence exists that these interventions are beneficial. The use of insulin sensitizers to target PCOS-related insulin resistance and metabolic dysfunction is common, but further studies on its use and effectiveness are warranted. SUMMARY: As a better understanding of adolescent PCOS evolves, including appropriate diagnostic criteria, factors associated with concomitant metabolic disorders and effective treatment options, improved care for these adolescents will be achieved. PMID- 22781075 TI - First analysis of the secretome of the canine heartworm, Dirofilaria immitis. AB - BACKGROUND: The characterization of proteins released from filariae is an important step in addressing many of the needs in the diagnosis and treatment of these clinically important parasites, as well as contributing to a clearer understanding of their biology. This report describes findings on the proteins released during in vitro cultivation of adult Dirofilaria immitis , the causative agent of canine and feline heartworm disease. Differences in protein secretion among nematodes in vivo may relate to the ecological niche of each parasite and the pathological changes that they induce. METHODS: The proteins in the secretions of cultured adult worms were run on Tris-Glycine gels, bands separated and peptides from each band analysed by ultra mass spectrometry and compared with a FastA dataset of predicted tryptic peptides derived from a genome sequence of D. immitis. RESULTS: This study identified 110 proteins. Of these proteins, 52 were unique to D. immitis. A total of 23 (44%) were recognized as proteins likely to be secreted. Although these proteins were unique, the motifs were conserved compared with proteins secreted by other nematodes. CONCLUSION: The present data indicate that D. immitis secretes proteins that are unique to this species, when compared with Brugia malayi. The two major functional groups of molecules represented were those representing cellular and of metabolic processes. Unique proteins might be important for maintaining an infection in the host environment, intimately involved in the pathogenesis of disease and may also provide new tools for the diagnosis of heartworm infection. PMID- 22781077 TI - Human papillomavirus vaccine in adolescent women: a 2012 update. AB - PURPOSE OF REVIEW: Despite recommendations from the Advisory Committee on Immunization Practices (ACIP) for routine vaccination of adolescents with the human papillomavirus (HPV) vaccine, U.S. coverage among women remains less than 50%, with that of adolescent men below 2%. RECENT FINDINGS: Ongoing studies document the efficacy and safety of the HPV vaccine. Nevertheless, misconceptions and negative attitudes persist and serve as barriers to vaccine uptake. Additionally, other factors such as age, insurance status, poverty status, and racial or ethnic background have been associated with diminished vaccine uptake and poor completion rates. Internationally, HPV vaccination programs and school based programs have achieved increased rates of uptake and series completion. HPV vaccination coverage may also be facilitated by improving communication between physicians, parents, and adolescents as well as by addressing common misconceptions about the vaccine. SUMMARY: This review highlights significant findings of recent literature on HPV vaccination of adolescent women with a special focus on uptake, series completion, communication, disparities in vaccine coverage, and other health outcomes associated with HPV vaccination. PMID- 22781078 TI - Long-acting reversible contraception for adolescents. AB - PURPOSE OF REVIEW: Teen pregnancy continues to plague the United States. This review will discuss long-acting reversible contraceptive (LARC) method use in teens, comprising intrauterine devices and subdermal implants. RECENT FINDINGS: The American College of Obstetricians and Gynecologists along with the American Academy of Pediatrics, the Centers for Disease Control, and the World Health Organization have recognized the potential impact of LARC (comprising intrauterine contraception and subdermal implants) to reduce unintended pregnancies. They have affirmed the safety of such devices, and no effects on long-term fertility have been identified. Teen users of these methods have been shown to have high continuation and satisfaction rates. On the contrary, oral contraceptive pills, the patch, and the contraceptive vaginal ring have significantly higher contraceptive failure rates, and these rates are magnified in young women. SUMMARY: LARC methods should be considered first-line options for teens seeking contraception. PMID- 22781079 TI - If I forget you, O Jerusalem, let my right hand forget its skill (Psalms 137:5). PMID- 22781080 TI - Relation of anterior vaginal mesh for pelvic organ prolapse repair to critical genital structures. PMID- 22781082 TI - Sexual pleasure during condom-protected vaginal sex among heterosexual men. AB - INTRODUCTION: Public health condom promotion efforts increasingly focus on the importance of sexual pleasure; however, little is known about sexual event specific factors that may increase or decrease perceptions of sexual pleasure when condoms are used. AIMS: To examine event-level factors associated with ratings of sexual pleasure during condom-protected vaginal intercourse. METHODS: Data were collected in 2008 from 1,875 men during a prospective daily diary study of sexual behavior and condom use. Sexual pleasure was assessed during condom protected vaginal intercourse considering situational, relational, intrapersonal, and behavioral predictors. Analyses were generalized estimating equation ordinal regression. MAIN OUTCOME MEASURES: Event-specific perceptions of sexual pleasure (three categories: not at all enjoyable to extremely enjoyable). RESULTS: Vaginal intercourse was reported on 29.8% (N = 8,876/29,714) of diary days; complete condom use was reported for 59.1% (5,249/8,876) of all vaginal intercourse events. This was confusing by using the word "all sexual events." Higher sexual pleasure ratings during complete condom use were associated with older age, manual stimulation of one's genitals, receiving oral sex, and performing oral sex. Sexual pleasure ratings also increased in association with intercourse duration, intercourse intensity, ejaculation, erection perception, and condom comfort. Sexual pleasure ratings were lower with erection difficulty and partner discomfort during sex. CONCLUSIONS: These data advance understanding of sexual pleasure during condom use, suggesting that sexual pleasure increases in conjunction with specific relational, physiological, and condom perceptions. These findings offer points upon which clinicians and health educators can engage men in an ongoing dialogue about augmenting sexual pleasure in the context of condom use. PMID- 22781084 TI - Radiation therapy in Peyronie's disease. AB - INTRODUCTION: Peyronie's disease (PD) is characterized by fibrotic plaque formation within the tunica albuginea, leading to penile deformity, angulation, painful erections, and often, erectile dysfunction. There is limited knowledge of its etiology and pathophysiology. Currently, there is no standardization for reporting the evaluation and treatment outcomes. No consensus exists on the ideal management of PD. AIM: The aim of this study is to review the use of radiation therapy (RT) for the treatment of PD. METHODS: This study used a review of the literature and informed expert opinion. MAIN OUTCOME MEASURES: The main outcome measures are the reported improvement with regard to pain, curvature, plaque size, and erectile function as well as a review of the safety profile of RT. RESULTS: Radiation has been used for the empirical treatment of PD with mixed results throughout the literature. Low-dose RT in the early stages of PD seems to be effective in patients with painful erections not improving with time or with the use of oral or intralesional therapies. Comparison with other current medical therapies is difficult due to the absence of criteria for therapeutic success and the absence of randomized, controlled trials. Multiple studies have demonstrated varied results in terms of curvature reduction, plaque volume, and sexual functioning. The absence of the use of validated means of measuring penile deformity and sexual function, the limited relevance of plaque and pain improvement combined with the potential negative consequences of radiation on erectile tissue structure and function lead us to make a recommendation that RT not be used for the management of PD. CONCLUSIONS: In clinical practice, mixed success for RT has led to the recommendation against its use as a treatment modality for PD. PMID- 22781083 TI - G-spot anatomy: a new discovery. AB - INTRODUCTION: The anatomic existence of the G-spot has not been documented yet. AIM: To identify the anatomic structure of the G-spot. METHODS: A stratum-by stratum vaginal wall dissection on a fresh cadaver. MAIN OUTCOME MEASURES: Primary outcome is the identification of the G-spot and the secondary outcome is its measurements and anatomic description of the G-spot. RESULTS: The G-spot has a distinguishable anatomic structure that is located on the dorsal perineal membrane, 16.5 mm from the upper part of the urethral meatus, and creates a 35 degrees angle with the lateral border of the urethra. The lower pole (tail) and the upper pole (head) were located 3 and 15 mm next to the lateral border of the urethra, respectively. Grossly, the G-spot appeared as a well-delineated sac with walls that resembled fibroconnective tissues and resembled erectile tissues. The superior surface of the sac had bluish irregularities visible through the coat. Upon opening the sac's upper coat, blue grape-like anatomic compositions of the G spot emerged with dimensions of length (L) of 8.1 mm * width (W) of 3.6-1.5 mm * height (H) of 0.4 mm. The G-spot structure had three distinct areas: the proximal part (the head) L 3.4 mm * W 3.6 mm, the middle part L 3.1 mm * W 3.3 mm, and the distal part (tail) L 3.3 mm * W 3.0 mm. From the distal tail, a rope-like structure emerged, which was seen for approximately 1.6 mm and then disappeared into the surrounding tissue. CONCLUSION: The anatomic existence of the G-spot was documented with potential impact on the practice and clinical research in the field of female sexual function. PMID- 22781085 TI - A review of the environmental safety of the PAT protein. PMID- 22781086 TI - Neonatal diabetes mellitus and congenital diaphragmatic hernia: coincidence or concurrent etiology? AB - Neonatal diabetes mellitus (NDM) is a rare metabolic disorder, affecting approximately 1 in 500,000 live births. The management of NDM is challenging, as the benefits of controlling hyperglycemia must be balanced with the risks of iatrogenic hypoglycemia. NDM occurs in both permanent and transient forms, which have been genetically and phenotypically well characterized. Herein, we present the previously unreported combination of transient NDM (TNDM) and congenital diaphragmatic hernia (CDH). In addition to reviewing the management and genetics of NDM we discuss the potential for overlapping genetic or embryologic abnormalities to explain the concurrence of CDH and NDM. PMID- 22781087 TI - Fabrication of high-resolution large-area patterns using EUV interference lithography in a scan-exposure mode. AB - Limited beam spot size is a major limitation of interference lithography. This limits the area of patterning and reduces the pattern homogeneity. We describe a scanning exposure technique to circumvent this problem. We show the generation of uniform and seamless gratings with half-pitches down to 35 nm over an area of several mm(2) using EUV interference lithography. The presented technique offers a fast and cost-effective method of fabricating one- and two-dimensional periodic nanostructures with improved uniformity and increased patterning area. PMID- 22781088 TI - Personalized medicine and access to health care: potential for inequitable access? AB - Personalized medicine promises that an individual's genetic information will be increasingly used to prioritize access to health care. Use of genetic information to inform medical decision making, however, raises questions as to whether such use could be inequitable. Using breast cancer genetic risk prediction models as an example, on the surface clinical use of genetic information is consistent with the tools provided by evidence-based medicine, representing a means to equitably distribute limited health-care resources. However, at present, given limitations inherent to the tools themselves, and the mechanisms surrounding their implementation, it becomes clear that reliance on an individual's genetic information as part of medical decision making could serve as a vehicle through which disparities are perpetuated under public and private health-care delivery models. The potential for inequities arising from using genetic information to determine access to health care has been rarely discussed. Yet, it raises legal and ethical questions distinct from those raised surrounding genetic discrimination in employment or access to private insurance. Given the increasing role personalized medicine is forecast to play in the provision of health care, addressing a broader view of what constitutes genetic discrimination, one that occurs along a continuum and includes inequitable access, will be needed during the implementation of new applications based on individual genetic profiles. Only by anticipating and addressing the potential for inequitable access to health care occurring from using genetic information will we move closer to realizing the goal of personalized medicine: to improve the health of individuals. PMID- 22781089 TI - Smoothed functional principal component analysis for testing association of the entire allelic spectrum of genetic variation. AB - Fast and cheaper next-generation sequencing technologies will generate unprecedentedly massive and highly dimensional genetic variation data that allow nearly complete evaluation of genetic variation including both common and rare variants. There are two types of association tests: variant-by-variant test and group test. The variant-by-variant test is designed to test the association of common variants, while the group test is suitable to collectively test the association of multiple rare variants. We propose here a smoothed functional principal component analysis (SFPCA) statistic as a general approach for testing association of the entire allelic spectrum of genetic variation (both common and rare variants), which utilizes the merits of both variant-by-variant analysis and group tests. By intensive simulations, we demonstrate that the SFPCA statistic has the correct type 1 error rates and much higher power than the existing methods to detect association of (1) common variants, (2) rare variants, (3) both common and rare variants and (4) variants with opposite directions of effects. To further evaluate its performance, the SFPCA statistic is applied to ANGPTL4 sequence and six continuous phenotypes data from the Dallas Heart Study as an example for testing association of rare variants and a GWAS of schizophrenia data as an example for testing association of common variants. The results show that the SFPCA statistic has much smaller P-values than many existing statistics in both real data analysis examples. PMID- 22781090 TI - A unique MSH2 exon 8 deletion accounts for a major portion of all mismatch repair gene mutations in Lynch syndrome families of Sardinian origin. AB - Lynch syndrome is an autosomal-dominant hereditary condition predisposing to the development of specific cancers, because of germline mutations in the DNA mismatch repair (MMR) genes. Large genomic deletions represent a significant fraction of germline mutations, particularly among the MSH2 gene, in which they account for 20% of the mutational spectrum. In this study we analyzed 13 Italian families carrying MSH2 exon 8 deletions, 10 of which of ascertained Sardinian origin. The overrepresentation of Sardinians was unexpected, as families from Sardinia account for a small quota of MMR genes mutation tests performed in our laboratory. The hypothesis that such a result is owing to founder effects in Sardinia was tested by breakpoint junctions sequencing and haplotype analyses. Overall, five different exon eight deletions were identified, two of which recurrent in families, all apparently unrelated, of Sardinian origin (one in eight families, one in two families). The c.1277 1180_1386+2226del3516insCATTCTCTTTGAAAA deletion shares the same haplotype between all families and appears so far restricted to the population of South West Sardinia, showing the typical features of a founder effect. The three non Sardinian families showed three different breakpoint junctions and haplotypes, suggesting independent mutational events. This work has useful implications in genetic testing for Lynch syndrome. We developed a quick test for each of the identified deletions: this can be particularly useful in families of Sardinian origin, in which MSH2 exon 8 deletions may represent 50% of the overall mutational spectrum of the four MMR genes causing Lynch syndrome. PMID- 22781091 TI - Atrioventricular canal defect in patients with RASopathies. AB - Congenital heart defects affect 60-85% of patients with RASopathies. We analysed the clinical and molecular characteristics of atrioventricular canal defect in patients with mutations affecting genes coding for proteins with role in the RAS/MAPK pathway. Between 2002 and 2011, 101 patients with cardiac defect and a molecularly confirmed RASopathy were collected. Congenital heart defects within the spectrum of complete or partial (including cleft mitral valve) atrioventricular canal defect were diagnosed in 8/101 (8%) patients, including seven with a PTPN11 gene mutation, and one single subject with a RAF1 gene mutation. The only recurrent mutation was the missense PTPN11 c.124 A>G change (T42A) in PTPN11. Partial atrioventricular canal defect was found in six cases, complete in one, cleft mitral valve in one. In four subjects the defect was associated with other cardiac defects, including subvalvular aortic stenosis, mitral valve anomaly, pulmonary valve stenosis and hypertrophic cardiomyopathy. Maternal segregation of PTPN11 and RAF1 gene mutations occurred in two and one patients, respectively. Congenital heart defects in the affected relatives were discordant in the families with PTPN11 mutations, and concordant in that with RAF1 mutation. In conclusion, our data confirm previous reports indicating that atrioventricular canal defect represents a relatively common feature in Noonan syndrome. Among RASopathies, atrioventricular canal defect was observed to occur with higher prevalence among subjects with PTPN11 mutations, even though this association was not significant possibly because of low statistical power. Familial segregation of atrioventricular canal defect should be considered in the genetic counselling of families with RASopathies. PMID- 22781092 TI - A novel LRSAM1 mutation is associated with autosomal dominant axonal Charcot Marie-Tooth disease. AB - Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuropathy resulting from mutations in >30 genes expressed in either the Schwann cells or the axon of peripheral nerves. The disease is classified into demyelinating (CMT1), axonal (CMT2) or intermediate (CMTI) based on electrophysiological and pathological findings. Our study focused on the identification of a novel disease mutation in a large Sardinian family with CMT2 of autosomal dominant (AD) inheritance. All available family members were clinically evaluated and samples were collected from consenting individuals. Initially, we excluded known CMT2 genes/loci in this family. We then conducted a genome-wide linkage analysis and mapped the gene to chromosome 9q33-q34. Refined linkage and haplotype analyses defined an 11.6-Mb candidate region with a maximum LOD score of 8.06. Following exclusion of several candidate genes from the region, we targeted the LRSAM1 (leucine-rich repeat and sterile alpha motif-containing 1) gene, very recently found to be associated with autosomal recessive CMT2 in one family. For a more efficient investigation of this large gene, already available proband RNA (cDNA) was initially analyzed. Targeted DNA analysis then confirmed a novel LRSAM1 splice-site (c.2047-1G>A) mutation, causing a frameshift that introduces a stop codon three amino acids further down the new reading frame (p.Ala683ProfsX3). This mutation is located in the C-terminal RING finger motif of the encoded protein and leads to premature truncation of the protein. In the course of our work, a second LRSAM1 mutation dominantly transmitted was identified by another group. Our data further confirms that LRSAM1 mutations are associated with CMT2 of AD inheritance. PMID- 22781093 TI - Adaptive clustering and adaptive weighting methods to detect disease associated rare variants. AB - Current statistical methods to test association between rare variants and phenotypes are essentially the group-wise methods that collapse or aggregate all variants in a predefined group into a single variant. Comparing with the variant by-variant methods, the group-wise methods have their advantages. However, two factors may affect the power of these methods. One is that some of the causal variants may be protective. When both risk and protective variants are presented, it will lose power by collapsing or aggregating all variants because the effects of risk and protective variants will counteract each other. The other is that not all variants in the group are causal; rather, a large proportion is believed to be neutral. When a large proportion of variants are neutral, collapsing or aggregating all variants may not be an optimal solution. We propose two alternative methods, adaptive clustering (AC) method and adaptive weighting (AW) method, aiming to test rare variant association in the presence of neutral and/or protective variants. Both of AC and AW are applicable to quantitative traits as well as qualitative traits. Results of extensive simulation studies show that AC and AW have similar power and both of them have clear advantages from power to computational efficiency comparing with existing group-wise methods and existing data-driven methods that allow neutral and protective variants. We recommend AW method because AW method is computationally more efficient than AC method. PMID- 22781094 TI - When access is an issue: exploring barriers to predictive testing for Huntington disease in British Columbia, Canada. AB - Predictive testing (PT) for Huntington disease (HD) requires several in-person appointments. This requirement may be a barrier to testing so that at risk individuals do not realize the potential benefits of PT. To understand the obstacles to PT in terms of the accessibility of services, as well as exploring mechanisms by which this issue may be addressed, we conducted an interview study of individuals at risk for HD throughout British Columbia, Canada. Results reveal that the accessibility of PT can be a barrier for two major reasons: distance and the inflexibility of the testing process. Distance is a structural barrier, and relates to the time and travel required to access PT, the financial and other opportunity costs associated with taking time away from work and family to attend appointments and the stress of navigating urban centers. The inflexibility of the testing process barrier relates to the emotional and psychological accessibility of PT. The results of the interview study reveal that there are access barriers to PT that deter individuals from receiving the support, information and counseling they require. What makes accessibility of PT services important is not just that it may result in differences in quality of life and care, but because these differences may be addressed with creative and adaptable solutions in the delivery of genetic services. The study findings underscore the need for us to rethink and personalize the way we deliver such services to improve access issues to prevent inequities in the health care system. PMID- 22781095 TI - Population studies: return of research results and incidental findings Policy Statement. AB - The Public Population Project in Genomics and Society (P3G) is a not-for profit international consortium with members from more than 40 countries. Its objective is to lead, catalyze, and co-ordinate international efforts and expertise in order to optimize the use of population studies, biobanks, research databases, and other similar health and social science research infrastructures. The year 2011-2012 witnessed a plethora of special issues of journals on the return of results but few discussed the particular situation of population studies that serve as resources for future unspecified research. P3G considers it important to propose a policy that distinguishes between the contexts of population research and disease (clinical) research involving patients and then delineates actual and future obligations. The objectives of this Policy Statement are to: (1) delineate the particular characteristics of population studies, (2) distinguish the circumstances surrounding access by researchers to such studies, and (3) develop a framework for the return of research results and incidental findings. PMID- 22781096 TI - A novel mitochondrial tRNA Arg mutation resulting in an anticodon swap in a patient with mitochondrial encephalomyopathy. AB - We report a mutation in the anticodon of the tRNA(Arg) gene (m.10437 G>A), resulting in an anticodon swap from GCU to ACU, which is the anticodon of tRNA(Trp), in a boy with mitochondrial encephalomyopathy. Enzyme histochemical analysis of muscle tissue and biochemical analysis of isolated muscle mitochondria demonstrated cytochrome c oxidase (COX) deficiency. Restriction fragment length polymorphism analysis showed that 90% of muscle and 82% of urinary epithelium mtDNA harbored the mutation. The mutation was not identified in blood, fibroblasts, hair roots, or buccal epithelial cells and it was absent in the asymptomatic mother, suggesting that it was a de novo mutation. Single fiber PCR analysis showed that the proportion of mutated mtDNA correlated with enzyme histochemical COX deficiency. This mutation adds to the three previously described disease-causing mutations in tRNA(Arg), but it is the first mutation occurring in the anticodon of tRNA(Arg). PMID- 22781097 TI - Clinical utility gene card for: Glanzmann thrombasthenia. PMID- 22781098 TI - Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies. AB - Identification of mutations in the HOGA1 gene as the cause of autosomal recessive primary hyperoxaluria (PH) type III has revitalized research in the field of PH and related stone disease. In contrast to the well-characterized entities of PH type I and type II, the pathophysiology and prevalence of type III is largely unknown. In this study, we analyzed a large cohort of subjects previously tested negative for type I/II by complete HOGA1 sequencing. Seven distinct mutations, among them four novel, were found in 15 patients. In patients of non consanguineous European descent the previously reported c.700+5G>T splice-site mutation was predominant and represents a potential founder mutation, while in consanguineous families private homozygous mutations were identified throughout the gene. Furthermore, we identified a family where a homozygous mutation in HOGA1 (p.P190L) segregated in two siblings with an additional AGXT mutation (p.D201E). The two girls exhibiting triallelic inheritance presented a more severe phenotype than their only mildly affected p.P190L homozygous father. In silico analysis of five mutations reveals that HOGA1 deficiency is causing type III, yet reduced HOGA1 expression or aberrant subcellular protein targeting is unlikely to be the responsible pathomechanism. Our results strongly suggest HOGA1 as a major cause of PH, indicate a greater genetic heterogeneity of hyperoxaluria, and point to a favorable outcome of type III in the context of PH despite incomplete or absent biochemical remission. Multiallelic inheritance could have implications for genetic testing strategies and might represent an unrecognized mechanism for phenotype variability in PH. PMID- 22781099 TI - Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility. AB - Wolfram syndrome (WFS) is a neurodegenerative genetic condition characterized by juvenile-onset of diabetes mellitus and optic atrophy. We studied clinical features and the molecular basis of severe WFS (neurodegenerative complications) in two consanguineous families from Iran. A clinical and molecular genetic investigation was performed in the affected and healthy members of two families. The clinical diagnosis of WFS was confirmed by the existence of diabetes mellitus and optic atrophy in the affected patients, who in addition had severe neurodegenerative complications. Sequencing of WFS1 was undertaken in one affected member from each family. Targeted mutations were tested in all members of relevant families. Patients had most of the reported features of WFS. Two affected males in the first family had fathered unaffected children. We identified two homozygous mutations previously reported with apparently milder phenotypes: family 1: c.631G>A (p.Asp211Asn) in exon 5, and family 2: c.1456C>T (p.Gln486*) in exon 8. Heterozygous carriers were unaffected. This is the first report of male Wolfram patients who have successfully fathered children. Surprisingly, they also had almost all the complications associated with WFS. Our report has implications for genetic counseling and family planning advice for other affected families. PMID- 22781100 TI - Using identity by descent estimation with dense genotype data to detect positive selection. AB - Identification of genomic loci and segments that are identical by descent (IBD) allows inference on problems such as relatedness detection, IBD disease mapping, heritability estimation and detection of recent or ongoing positive selection. Here, employing a novel statistical method, we use IBD to find signals of selection in the Maasai from Kinyawa, Kenya (MKK). In doing so, we demonstrate the advantage of statistical tools that can probabilistically estimate IBD sharing without having to thin genotype data because of linkage disequilibrium (LD), and that allow for both inbreeding and more than one allele to be shared IBD. We use our novel method, GIBDLD, to estimate IBD sharing between all pairs of individuals at all genotyped SNPs in the MKK, and, by looking for genomic regions showing excess IBD sharing in unrelated pairs, find loci that are known to have undergone recent selection (eg, the LCT gene and the HLA region) as well as many novel loci. Intriguingly, those loci that show the highest amount of excess IBD, with the exception of HLA, also show a substantial number of unrelated pairs sharing all four of their alleles IBD. In contrast to other IBD detection methods, GIBDLD provides accurate probabilistic estimates at each locus for all nine possible IBD sharing states between a pair of individuals, thus allowing for consanguinity, while also modeling LD, thus removing the need to thin SNPs. These characteristics will prove valuable for those doing genetic studies, and estimating IBD, in the wide variety of human populations. PMID- 22781101 TI - A human autophagy interaction network. AB - The original "Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes" has been well received and used by many researchers and authors. I consider these to be very important guidelines that require a consensus among the researchers in the field, because they are used by authors to defend against inappropriate reviewers' comments, and by reviewers to point out to editors the flaws in research papers. Accordingly, I decided it was time to revise and update the guidelines. After all, the field has expanded substantially, as has the range of model systems being used to analyze autophagy. As a result, the list of authors has similarly increased. In addition, this version of the guidelines is not limited to higher eukaryotes nor to macroautophagy. Here, I explain the approach used to invite authors to participate in the revised guidelines, and briefly demonstrate one aspect of their utility. PMID- 22781103 TI - Relationships between depressive symptoms and self-reported unintentional injuries: the cross-sectional population-based FIN-D2D survey. AB - BACKGROUND: There is a lack of knowledge on the influence of different levels of physical activity (PA) on unintentional injuries among those with depressive symptoms (DS). The aim of this study was to evaluate the relationship between PA categories and unintentional injuries among participants with and without DS based on a cross-sectional population-based FIN-D2D survey conducted in 2007. METHODS: Out of 4500, 2682 participants (60%) aged 45-74 years attended in this study. The unintentional injuries over the past year were captured in a questionnaire. DS were determined with the Beck Depression Inventory (>= 10 points) and PA with the International Physical Activity Questionnaire. The statistical significance between DS and unintentional injury categories was evaluated by using t-test, chi-square test, or permutation test, analysis of covariance, or regression models. The factors related to unintentional injuries were estimated by univariate and multivariate logistic regression models. RESULTS: The proportion of subjects with unintentional injuries was higher among those with DS (17%) compared to those without DS (10%) (age- and gender-adjusted p = 0.023). The median (range) number of activity-loss days after injury was 22 (0-365) in participants with DS and 7 (0-120) in participants without DS ( p = 0.009). The percentage of subjects with unintentional injuries was not significantly different between PA categories in participants with DS and without DS. A stepwise multivariate logistic regression analysis showed that DS, functional ability, and musculoskeletal diseases were related to unintentional injuries. CONCLUSIONS: PA level was not related to unintentional injuries, whereas those with DS had a higher prevalence of unintentional injuries and prolonged activity-loss after injury. These results underline the importance of injury prevention, especially among those who have DS and additional risk factors. PMID- 22781104 TI - Effect of percutaneous tracheostomy on gas exchange in hypoxemic and non hypoxemic mechanically ventilated patients. AB - BACKGROUND: The influence of percutaneous tracheostomy on ventilator-dependence and clinical outcomes has been investigated in a number of studies. However, except for the variations during the procedure, the impact of tracheostomy on gas exchange has been scarcely explored. We investigated the effect of tracheostomy on respiratory function in a cohort of ICU patients. METHODS: In this retrospective study, clinical records of 107 patients from a general ICU and neurosurgical ICU who underwent percutaneous tracheostomy were reviewed to compare ventilator setting, gas exchange, and hemodynamic parameters on the day before and on the day after the procedure. Further, a pre-established subgroup analysis on hypoxemic patients (Pao2/Fio2 < 300 mm Hg) was performed. RESULTS: Among all patients analyzed, a marginal decrease in Paco2 (43 +/- 9 mm Hg vs 42 +/- 7 mm Hg, before vs after P = .004) and an increase in pH (7.43 +/- 0.04 vs 7.44 +/- 0.03, before vs after P = .03) were observed after tracheostomy. In the subgroup of hypoxemic patients (n = 38), after the tracheostomy an increase in Pao2/Fio2 (222 +/- 60 mm Hg vs 256 +/- 84 mm Hg, before vs after P = .001) and a decrease in Paco2 (46 +/- 11 mm Hg vs 43 +/- 9 mm Hg, before vs after P = .001) were found. CONCLUSIONS: Percutaneous tracheostomy did not worsen gas exchange in a cohort of ICU patients. In hypoxemic patients, tracheostomy appeared to improve oxygenation and ventilation. PMID- 22781105 TI - The flavonoid morin restores blood pressure and lipid metabolism in DOCA-salt hypertensive rats. AB - OBJECTIVE: This study was undertaken to investigate the antihypertensive and antihyperlipedimic potential of morin against deoxycorticosterone acetate (DOCA) salt hypertensive rats. METHODS: Hypertension was induced in uninephrectomized rats (UNX) by weekly twice subcutaneous injection of DOCA (25 mg/kg) and 1% NaCl in the drinking water for six consecutive weeks. Morin (50 mg/kg) was administered to DOCA-salt rats orally using an intragastric tube daily for a period of 6 weeks. RESULTS: The DOCA-salt hypertensive rats showed significant elevation in mean arterial pressure (MAP), heart rate (HR) and reduction in body weight. A significant increase in the concentrations of plasma and tissue (liver, kidney, heart, and aorta) lipids such as total cholesterol, triglycerides, free fatty acids, phospholipids, plasma low-density and very low-density lipoproteins cholesterol, and a decrease in the concentration of high-density lipoprotein cholesterol were noticed in DOCA-salt hypertensive rats. Also, the levels of urinary protein and the activity of 3-hydroxy 3-methylglutaryl coenzyme A reductase in the plasma and tissues were increased, and lecithin cholesterol acyl transferase activity in the plasma was decreased in DOCA-salt rats. Morin supplementation (50 mg/kg) throughout the experimental period restored all the above parameters significantly. CONCLUSION: Morin has a potential role in attenuating severe hypertension and hyperlipedimia. PMID- 22781106 TI - Morning headaches in snorers and their bed partners: a prospective diary study. AB - BACKGROUND: The prevalence and characteristics of morning headaches (MH) in habitual snorers are not well known, with only one retrospective study reporting MH in 23.5% of snorers. The role of MH in bed partners of snorers has not yet been examined. Therefore, the objective of this study was to assess MH prospectively in habitual snorers and their bed partners. METHODS: We recruited habitual snorers and their bed partners via newspaper articles. The participants completed a semistructured interview, filled in questionnaires about sleep quality, daytime sleepiness, depression and anxiety and kept a 90-day headache and sleep diary. RESULTS: We included a total of 102 snorers and 63 bed partners. Seventy-six snorers (25 female) and 41 bed partners (31 female) completed the study, recording a total of 6690 and 3497 diary days, respectively. MH was present on at least 1 day in 57% of the snorers and in 61% of the bed partners and recorded on 7.2% and 3.6% of the diary days, respectively. Independent predictors of MH in snorers were pre-study headache frequency (p < 0.001), anxiety disorder (p < 0.001), waking up because of pain (p = 0.002) and waking up too early (p < 0.001); and independent predictors in bed partners were migraine (p = 0.02), difficulties breathing during sleep (p < 0.001), waking up because of pain (p = 0.01) and waking up too early (p < 0.001). The analysis of couples only (n = 41) revealed pre-study headache frequency (p < 0.001), waking up too early (p < 0.001) and nocturnal confusion (p < 0.001) as independent predictors of MH in snorers, and migraine (p = 0.02), difficulties breathing during sleep (p < 0.001), waking up because of pain (p = 0.01) and waking up too early (p < 0.001) as independent predictors in bed partners. DISCUSSION: MH shows a 90-day prevalence of around 60% in habitual snorers as well as in their bed partners. Predictors of MH are related to sleep, headache and psychiatric comorbidity. PMID- 22781107 TI - [Management of pregnancy with myasthenia gravis: 7 cases report]. AB - OBJECTIVE: To discuss the interaction of pregnancy and myasthenia gravis (MG) and the management of pregnancy with MG. METHODS: Seven cases of pregnancy with MG in Peking Union Medical College Hospital were analyzed retrospectively, with respect to the therapy of MG, pregnancy complications and outcomes. RESULTS: Totally 38,683 pregnant women were admitted to Peking Union Medical College Hospital between Oct. 1983 and Oct. 2010. Among them there were 9 patients suffered from MG, with the incidence of 0.023%. Two pregnancies were terminated because of personal reasons, and seven continued. (1) Onset of MG: in the 7 cases, 6 were diagnosed before conception, with the mean course of 5.9 years. The other one occurred in the third trimester. (2) MANAGEMENT: all the cases were under close surveillance during pregnancy. Four women took thymectomy before conception, and one of them kept taking medication after surgery. In those who received thymectomy, 3 cases remained stable and 1 case worsened during pregnancy. The latter one took medication at 33 weeks, and continued to full term. MG exacerbated in the other three women who had not undergone thymectomy before conception. Among them, one woman complicated with systemic lupus erythematosus and lupus nephritis delivered the baby at 31 weeks. (3) Delivery and neonatal outcomes: cesarean deliveries were performed in 5 cases and the other two underwent vaginal deliveries. All the newborns were admitted to neonatal intensive care unit for surveillance. There were three smaller than gestational week (SGA) infants. No MG was observed in newborns. CONCLUSIONS: Patients with MG should have an overall evaluation before conception. The course of MG during pregnancy is unpredictable. They may get a promising outcome under the control of a multidisciplinary team including obstetricians and neurologists. Newborns should be carefully monitored for sings of transitory MG in the department of pediatrics. PMID- 22781108 TI - [Comparison of GnRH antagonist fixed protocol and GnRH agonists long protocol in infertile patients with normal ovarian reserve function in their first in vitro fertilization-embryo transfer cycle]. AB - OBJECTIVE: To compare the clinical outcomes of gonadotropin-releasing hormone (GnRH) antagonist (GnRH-ant) fixed protocol with GnRH agonist (GnRH-a) long protocol in infertile patients with normal ovarian reserve function in their first in vitro fertilization-embryo transfer (IVF-ET) cycle, and to explore the feasibility and advantage of GnRH antagonist protocol performed in normal responders. METHODS: From January 2011 to June 2011, 771 infertile women with normal ovarian reserve function underwent their first IVF or intracytoplasmic sperm injection (ICSI) cycles in Peking University Third Hospital, which were divided into 245 cycles in GnRH-ant fixed protocol group (GnRH-ant group) and 526 cycles in GnRH-a long protocol group (GnRH-a group). The data of general demographic, treatment and clinical outcome were compared between two groups. RESULTS: Age, infertile duration, body mass index (BMI), baseline serum follicle stimulating hormone (FSH) and estradiol levels between two groups did not reached statistical difference (P > 0.05). The level of estradiol was (12 289 +/- 6856) pmol/L in GnRH-ant group and (14 934 +/- 8007) pmol/L in GnRH-a group at day of hCG injection. The mean length of stimulation was (10.3 +/- 1.2) days in GnRH-ant group and (12.8 +/- 1.6) days in GnRH-a group. The dose of gonadotropin was (2013 +/- 607) U in GnRH-ant group and (2646 +/- 913) U in GnRH-a group. The number of ovum was 15 +/- 7 in GnRH-ant group and 17 +/- 8 in GnRh-a group. Those clinical parameter all reached statistical difference (P < 0.05). The number of embryo was 7 +/- 4 in GnRH-ant group and 8 +/- 5 in GnRH-a group, the rate of clinical pregnancy was 40.9% (94/230) in GnRH-ant group and 45.6% (216/474) in GnRH-a group, the rate of implantation was 26.1% (128/490) in GnRH-ant group and 30.9% (307/994) in GnRH-a group, the rate of continuing pregnancy was 38.7% (89/230) in GnRH-ant group and 42.6% (202/474)in GnRH-a group, those parameter did not reach statistical difference (P > 0.05). The rate of moderate or severe ovarian hyperstimulation syndrome was 2.4% (6/245) in GnRH-ant group and 4.2% (22/526) in GnRH-a group, which did not show significant difference (P > 0.05). CONCLUSION: In the first IVF or ICSI cycle of the patients with normal ovarian reserve function, the fixed GnRH-ant protocol could get the same satisfied clinical outcome, and it is more economic, convenient and safer compared with low dose depot GnRH-a long protocol. PMID- 22781109 TI - [Study on clinical effect on infertility women with polycystic ovary syndrome treated by in vitro maturation and in vitro fertilization-embryo transfer]. AB - OBJECTIVE: To compare clinical and laboratory outcomes of in vitro maturation (IVM) with in vitro fertilization-embryo transfer (IVF-ET) in treatment of infertility associated with polycystic ovary syndrome (PCOS). METHODS: From Jan.2007 to Dec.2010, infertile patients with PCOS underwent 701 cycles in First Affiliated Hospital of Wenzhou Medical College were studied retrospectively. Those were divided into 293 cycles of IVM group and 408 cycles of IVF/intra cytoplasmic sperm injection (ICSI) group. The average transplantation rate, mean number of retrieval oocytes, maturation rate, fertilization rate, cleavage rate, high quality embryo rate, embryo implantation rate, pregnancy rate per transfer, pregnancy outcomes and incidence of ovarian hyperstimulation syndrome (OHSS) of the two methods of treatment were compared between two groups. RESULTS: There were 275 cycles in IVM group and 342 cycles in IVF/ICSI group established embryo transfer. The transplantation rate was 93.9% (275/293) in IVM group and 83.8% (342/408) in IVF/ICSI, which reached statistical difference (P < 0.01). The maturation rate of 56.64%, cleavage rate of 88.08%, high quality embryo rate of 38.72% and embryo implantation rate of 17.8% in IVM group were significantly lower than 91.09%, 94.91%, 51.50% and 25.4% in IVF/ICSI group (all P < 0.01). The clinical pregnancy rate per transfer were 37.8% (104/275) in IVM group and 44.2% (151/342) in IVF/ICSI group, which did not show statistical difference (P > 0.05). The mean number of oocytes (12.9 +/- 6.5 vs. 12.9 +/- 7.9) and fertilization rate (76.52% vs. 70.75%) didn't show significant difference between IVM group and IVF/ICSI group (P > 0.05). The 21.3% (87/408) cycles presented mild to moderate OHSS and 2.0% cycles (8/408) presented severe OHSS in IVF/ICSI group. While, no OHSS cycles were observed in IVM group. CONCLUSION: IVM could get similar clinical pregnancy rates compared with IVF/ICSI in patient with PCOS, however, it can avoid occurrence of OHSS. PMID- 22781110 TI - [Clinical value of anti-adhesion agents used in laparotomy in obstetrics and gynecology]. AB - OBJECTIVE: To investigate clinical value of anti-adhesion agent:chitosan in preventing adhesions followed by laparotomy surgery in obstetrics and gynecology. METHODS: From Jan. 2006 to Dec. 2009, 770 patients underwent laparotomy surgery at Department of Obstetrics and Gynecology in the Second Affiliated Hospital of Harbin Medical University. One hundred and twenty-five patients underwent secondary surgery due to disease recurrence or cesarean section, the previous surgery were 18 cases with myomectomy, 20 cases with endometriosis surgery, 5 cases with resection of pelvic abscess, 20 cases with ectopic pregnancy surgery, 27 cases with benign adnexal neoplasm resection, 9 cases with cyto-reductive surgery in ovarian cancer, 26 cases with variable infertility surgery. Those 125 patients were managed by different agents washing before abdomen closure, which were assigned into two groups, including 59 cases washed by saline in control group and 66 cases washed by chitosan in study group. The abdomen adhesion in secondary surgery was evaluated by adhesion classification system. RESULTS: In study group, 37 patients without adhesions, 20 patients with degree I adhesion, 6 patients with degree II adhesion, 3 patients with degree III adhesion, and no patients with degree IV adhesion were observed. While in control group, there were 11 patients without adhesions, 23 patients with degree I adhesion, 14 patients with degree II adhesion, 8 patients with degree III adhesion, and 3 patients with degree IV adhesion. The distribution of adhesion reached statistical significance between the two groups (chi(2) = 20.9999, P = 0.0003). Twenty-six patients in previous surgeries due to infertility included 17 cases in control group and 9 cases in study group. They all were managed by cesarean section in secondary surgery, it was found that 15 cases without adhesion and 2 cases with degree I adhesion were in study group and 2 cases without adhesion and 7 cases with degree I adhesion were in control group. It reached statistical difference (P = 0.0016). CONCLUSION: Anti-adhesion agent could prevent adhesion followed by surgery in obstetrics and gynecology effectively. PMID- 22781111 TI - [Significance of DNA ploidy analysis in diagnosis of ASCUS]. AB - OBJECTIVE: To investigate the significance of DNA ploidy analysis in diagnosis of atypical squamous cell of undetermined significance (ASCUS). METHODS: From Jan.2009 to Jul.2011, 875 women with ASCUS confirmed by liquid based thin layer cytology technique underwent DNA ploid analysis in Hubei Maternal and Child Health Hospital. Among 294 women underwent high risk HPV detection. All subjective were examined colposcopy directed biopsy at day 3 to 10 after menstruation. RESULTS: Among 875 ASCUS cases, 553 cases with histologically as chronic cervicitis (63.2%), 165 cases with cervical intraepithelial neoplasia (CIN)I (18.9%), 45 cases with CINII (5.1%), 79 cases with CINIII (9.0%) and 33 cases with cervical invasive cancer (3.8%) were confirmed by colposcopy. Totally 532 cases were observed with DNA heteroploid, and 343 were not observed with DNA heteroploid. When DNA heteroploid negative and more than or equal to three ploid were used to predict CINII or more severe cervical diseases, the sensitivity, specificity, positive predictive values and negative predictive values were 98.7% and 90.3%, 47.5% and 46.1%, 29.1% and 40.8%, 99.4% and 92.1%, respectively. The amount of heteroploid cells > 2.5c and > 5c among every 100 detected cells in chronic cervicitis and CINI, CINII, CINIII and cervix cancer were respectively 2.53 +/- 1.99 and 0.10 +/- 0.07, 2.24 +/- 1.69 and 0.20 +/- 0.11, 4.10 +/- 1.91 and 0.28 +/- 0.19, 7.97 +/- 7.33 and 1.27 +/- 1.23, 8.99 +/- 7.33 and 0.36 +/- 0.33, there was no statistical difference in amount of heteropolid cells between >2.5c and > 5c at group of chronic cervicitis and CINI, CINIII and cervix cancer (P > 0.05). However, the amount of heteroploid cells at > 2.5c and > 5c at group of chronic cervicitis, CINI, CINIII and cervical were higher than that of CINII significantly (P < 0.05). Among 294 cases with high risk (HR) HPV detection, 216 cases were HR-HPV positive, and 78 cases were HR-HPV negative. The pathology result by colposcopy at group of negative heteroploid, heteroploid < 3, or >= 3 showed statistical distribution (chi(2) = 115.2775, P < 0.01). CONCLUSION: DNA ploidy analysis can be used for ASCUS diagnosis, which can avoid excessive biopsy under colposcopy, in the mean time, CIN and cervical cancer could decrease missed diagnosis. PMID- 22781112 TI - [Analysis of the status of DACH1 gene promoter methylation in endometrial carcinoma and its clinical significance]. AB - OBJECTIVE: To analyze the status of DACH1 gene promoter methylation and explore its association with the expression of DACH1 gene promoter methylation and clinical significance of endometrium carcinoma (EC). METHODS: From February 2004 to August 2008, a total of 80 EC tissue samples with comprehensive surgical pathology staging were collected and used for this study. Twenty normal endometrium tissues in 2008 were abstained from the fractional curettage because of dysfunctional uterine bleeding as control. All samples were confirmed pathologically. Methylation specific PCR (MSP) was performed to detect the promoter methylation of DACH1 gene, and analyze its influence on the expression of DACH1 and the relationship between DACH1 promoter methylation and clinicopathological factors in EC. DACH1 protein expression was detected by western blot. Chi-square test and Pearson test were used for statistical analysis. RESULTS: The rate of promoter methylation of DACH1 gene in the EC tissues was significantly higher than that in the normal endometrium issues (30% vs. 5%, P < 0.05). There was an association between the expression of DACH1 and DACH1 gene promoter methylation (r = -0.30, P < 0.01). There was statistical difference between the methylation of DACH1 and the pathological grade (P < 0.05) or histological type (P < 0.05). But DACH1 gene methylation was not related with the age, stage, myometrial invasion depth and lymphnode metastasis (P > 0.05). CONCLUSIONS: DACH1 gene promoter methylaion could lead to a decrease or absence in the DACH1 expression in EC. The promoter methylation of DACH1 gene may induce the inhibition of DACH1 expression, which might be one of the mechanisms of DACH1 gene inactivation in human EC. PMID- 22781113 TI - [Study on the oxidative stress and inflammation in trophoblast cells stimulated by different chain length fatty acids]. AB - OBJECTIVE: To investigate the oxidative stress and inflammation in trophoblast cells stimulated by different chain length fatty acids. METHODS: Serum-free trophoblast cells cultured in vitro were divided into five groups, which were incubated with DMEM medium without free fatty acid (F-FFA), short chain fatty acids (SC-FFA), medium chain fatty acids (MC-FFA), long chain fatty acids (LC FFA), very long chain fatty acids (VLC-FFA). Then cells in each group were stimulated by DMEM medium, reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (apocynin) and p38 mitogen-activated protein kinases (p38MAPK) inhibitor (SB203580) and were subdivided as each FFA plus-DMEM group, plus-NADPH-I and plus-p38MAPK-I groups. Expressions of mRNA and protein of p38MAPK and cyclooxygenase 2 (COX-2) in trophoblast cells were detected by real time PCR and western blot. RESULTS: (1) The mRNA expression of p38MAPK in LC-FFA + DMEM, VLC-FFA + DMEM, LC-FFA + NADPH-I, LC-FFA + p38MAPK-I, VLC-FFA + NADPH-I, VLC-FFA + p38MAPK-I group were 4.56 +/- 0.28, 22.65 +/- 2.40, 0.87 +/- 0.06, 1.02 +/- 0.15, 19.87 +/- 1.93, 10.22 +/- 0.75 separately, and the protein expressions were 0.79 +/- 0.02, 0.93 +/- 0.10, 0.43 +/- 0.06, 0.44 +/- 0.19, 0.79 +/- 0.10, 0.81 +/- 0.14. Compared with other groups, the mRNA and protein expressions of p38MAPK in LC-FFA + DMEM, VLC-FFA + DMEM group were increased (P < 0.05). Compared with LC-FFA + DMEM group, mRNA and protein expressions of p38MAPK in LC FFA + NADPH-I and LC-FFA + p38MAPK-I group were significantly decreased (P < 0.05). Compared with VLC-FFA + DMEM group, mRNA and protein expressions of p38MAPK had no difference in VLC-FFA + NADPH-I group (P > 0.05), mRNA expression of p38MAPK in VLC-FFA + p38MAPK-I group was significantly decreased (P < 0.05), but there was no difference in protein expression (P > 0.05). (2) The mRNA expression of COX-2 in LC-FFA + DMEM, VLC-FFA + DMEM, LC-FFA + NADPH-I, LC-FFA + p38MAPK-I, VLC-FFA + NADPH-I, VLC-FFA + p38MAPK-I group were 3.97 +/- 0.03, 39.08 +/- 0.63, 0.99 +/- 0.13, 0.98 +/- 0.18, 20.93 +/- 3.70, 13.46 +/- 2.31 separately, and the protein expressions were 1.32 +/- 0.20, 1.33 +/- 0.25, 0.59 +/- 0.13, 0.58 +/- 0.30, 0.88 +/- 0.18, 0.91 +/- 0.24. Compared with other groups, mRNA and protein expressions of COX-2 in LC-FFA + DMEM and VLC-FFA + DMEM group were significantly increased (P < 0.05). Compared with LC-FFA + DMEM group, mRNA and protein expressions of COX-2 in LC-FFA + NADPH-I and LC-FFA + p38MAPK-I group were decreased (P < 0.05). Compared with VLC-FFA + DMEM group, mRNA and protein expressions of COX-2 in VLC-FFA + NADPH-I and VLC-FFA + p38MAPK-I group were all decreased (P < 0.05). (3) The correlation analysis showed that there were significantly positive correlations between the mRNA and protein expressions of p38MAPK and COX-2 in LC-FFA group (P < 0.05). There were significantly positive correlations in protein expression (P < 0.05), but no correlation in the mRNA expression between p38MAPK and COX-2 in the F-FFA, SC-FFA, MC-FFA, VLC-FFA groups (P > 0.05). CONCLUSIONS: The oxidative stress and inflammation may exist in trophoblast cells which were stimulated by LC-FFA and VLC-FFA. p38MAPK signal transduction pathway may contributed in this process. PMID- 22781115 TI - [Analysis of the characteristics of side population cells in the human ovarian cancer cell line OVCAR-3]. AB - OBJECTIVE: To identify the presence of side population (SP) cells in human ovarian cancer cell line OVCAR-3 and to investigate whether SP cells have the characteristics of cancer stem cells. METHODS: SP and non-SP (NSP) cells from OVCAR-3 were isolated by fluorescence-activated cell sorting after being stained by DNA-binding dye Hoechst 33342. Limiting dilution transplantation assay, real time PCR, and drug sensitivity assay were performed to compare the tumorigenic ability, differentiation ability in vivo, the mRNA expression of "stemness" marker (Oct-4, Klf4, and Nanog) and ATP-binding cassette (ABC) transporter (ABCG2, ABCB1, and ABCC2), and response to multiple drugs (cisplatin, paclitaxel, doxorubicin, and mitoxantrone) between SP and NSP cells. RESULTS: A few of SP cells [(1.13 +/- 0.39)%] which were sensitive to reserpine were identified in OVCAR-3 cells. The injection of as few as 10(2) SP cells initiated tumors in two of five mice. Tumor latency was 52 - 61 days. However, the NSP cells did not generate any tumors in mice until 10(4) NSP cells were injected (two of five mice). Tumor latency was 64 - 98 days. Tumorigenicity of SP cells was enhanced by at least 100-fold than that of NSP cells. The SP cells regenerated both SP [(2.09 +/- 0.73)%] and NSP populations in vivo with a fraction size that was comparable to the original population. The mRNA expression of "stemness" genes Oct-4, Klf4 and ABC transporters ABCG2, ABCC2 genes were elevated in SP cells compared to NSP cells, the fold changes were 1.95 +/- 0.41 (P < 0.05), 4.26 +/- 0.63 (P < 0.01), 3.22 +/- 0.36 (P < 0.01), and 1.76 +/- 0.26 (P < 0.01), respectively. The relative activity of SP and NSP cells were 0.757 +/- 0.105 versus 0.474 +/- 0.035 (P < 0.01), 0.521 +/- 0.092 versus 0.384 +/- 0.073 (P < 0.05), 0.742 +/- 0.051 versus 0.526 +/- 0.088 (P < 0.01), and 0.690 +/- 0.096 versus 0.466 +/- 0.112 (P < 0.01) when they exposed to 0.25 ug/ml cisplatin, 0.01 umol/L paclitaxel, 0.25 umol/L doxorubicin, and 0.05 ug/ml mitoxantrone, respectively. CONCLUSIONS: SP cells from OVCAR-3 have enhanced self-renewal, differentiation, and tumor initiating capacity compared to NSP cells. The mRNA expression of stemness genes and ABC transporters are markedly elevated in SP cells, which showed resistance to multiple chemotherapeutic drugs and have characteristics of cancer stem-like cells. Therefore, SP phenotype could be used as a marker to isolate the cancer stem-like cells in ovarian cancer. PMID- 22781114 TI - [Establishment of damaged endometrial stromal cells model in vitro]. AB - OBJECTIVE: To investigate the method of establishing damaged endometrial stromal cells (ESC) model in vitro. METHODS: (1) From June to December 2011 ESC from normal endometrim at proliferation phase (n = 8) and secretory phase (n = 8) were isolated, cultured and identified in vitro. (2) ESC was treated with different concentrations of mifepristone or withdrawal of mifepristone at different time point. The proliferation inhibition percent was measured by cell counting kit-8 (CCK-8). (3) 0 umol/L(control group)and 60 umol/L (experimental group) concentration of mifepristone was added into ESC for 48 hours, then withdrew of mifepristone, continued to be cultured for 48 hours. The morphological changes were observed and apoptosis of ESC in different menstrual cycle were detected by flow cytometry. The mRNA and protein level of vascular endothelial growth factor (VEGF), caspase-3, 8, and 9 were determined by one-step quantitative real-time PCR (Q-PCR) and western blot. RESULTS: (1) ESC from 16 specimens of endometrium were all isolated and cultured successfully. (2) The proliferation inhibition rate of ESC was correlated with concentration and duration of mifepristone positively. The proliferation of ESC could be recovered at a range of time after withdrawal of mifepristone. However, when the concentration of mifepristone was 100 umol/L, the growth of ESC recovered very hardly. (3) The damaged ESC spacing increased, the spindle shape and vacuolization in the cytoplasm were observed in experimental group; the rate of apoptosis of these damaged cells was significantly increased compared with control groups, which were (52 +/- 12)% vs. (13 +/- 5)% at the proliferative phase and (53 +/- 6)% vs. (32 +/- 3)% at the secretory phase (all P < 0.05). The relative mRNA level of VEGF was 0.52 +/- 0.12 in experimental group and 1.00 +/- 0.17 in control group at proliferation phase (P < 0.05). And the relative mRNA level of VEGF was 0.19 +/- 0.03 in experimental group and 0.81 +/- 0.07 in control group at secretory phase (P < 0.05). The relative level of VEGF protein in the experimental group were both decreased 1.98 and 2.79 folds at the proliferation phase and the secretory phase when compared with those in control group, respectively (P < 0.05). While the relative levels of caspase-3, 8, 9 mRNA were 5.62 +/- 0.65, 5.41 +/- 0.53, 7.22 +/- 0.51 in the experimental group and 1.00 +/- 0.44, 1.00 +/- 0.21, 1.00 +/- 0.32 in control group at the proliferative phase. In the mean time, the relative levels of caspase-3, 8, 9 mRNA were 10.22 +/- 0.72, 25.3 +/- 1.72, 9.48 +/- 1.89 in experimental group and 1.42 +/- 0.14, 1.14 +/- 0.28, 1.16 +/- 0.12 in control group at the secretory phase, respectively (P < 0.05). Compared with the control group, the levels of caspase protein in the experimental group were increased 2.04 and 1.60 folds in caspase-3, 4.23 and 1.49 folds in caspase-8, 2.65 and 3.5 folds in caspase-9 at the proliferative phase and at the secretory phase, respectively (P < 0.05). CONCLUSION: The damaged model of ESC can be established after 48 hours by the withdrawal of 60 umol/L mifepristone in treatment of ESC for 48 hours. PMID- 22781116 TI - [Effect of XPG down-regulation gene expression towards the proliferation of epithelial ovarian cancer cells and its chemosensitivity to platinum]. AB - OBJECTIVE: To investigate the effect of XPG down-regulation gene expression towards the proliferation of epithelial ovarian cancer cells and its chemosensitivity to platinum. METHODS: The small interference RNA (siRNA)-XPG fragments were designed and tranfected into SKOV3/DDP cell lines by lipofectamine transiently for choosing the best siRNA-XPG fragment to silence XPG gene expression. The pGPU6/GFP/Neo vector was used to construct the siRNA-XPG vectors, which was transfected into SKOV3/DDP cell line with expression of XPG gene. Real time PCR and western blot were employed to confirm the silencing efficacy of siRNA-XPG. The growth curve of cells, cell cycle, the drug-resistance index of cells and intracellular drug concentration were measured by 4-methyl-thiazolyl tetrazolium (MTT), flow cytometer (FCM) and high performance liguid chromatograph respectively. RESULTS: (1) Real-time PCR results showed that XPG mRNA expression copy number in SKOV3/DDP tranfected with siRNA-XPG-733 fragment was 1.050 +/- 0.023, which was significantly lower than that in SKOV3/DDP tranfected with other siRNA-XPG fragments (P < 0.05, respectively), and was chosed to construct the siRNA-XPG vectors. The XPG mRNA expression was down-regulated in short hairpin RNA (shRNA)-XPG-733-SKOV3/DDP cell lines that confirmed by western blot. (2) The growth curve showed that growth velocity of shRNA-XPG-733-SKOV3/DDP cell lines was lower than that of shRNA-GAPDH and shRNA-NC cell lines (P < 0.05, respectively). The results of FCM also showed that 34.0% of cells in shRNA-XPG 733-SKOV3/DDP cell lines were in S + G(2)/M phase, while only 58.7% and 51.3% in shRNA-GAPDH and shRNA-NC cell lines respectively (P < 0.05, respectively). (3) The drug-resistance index of shRNA-XPG-733-SKOV3/DDP cell lines [50% inhibiting concertration (IC(50)): (13.79 +/- 0.06) ug/ml] was lower than that in shRNA GAPDH and shRNA-NC cell lines [IC(50): (27.84 +/- 0.34) ug/ml and (28.32 +/- 0.42) ug/ml, respectively] statistically significant (P < 0.05, respectively); but there was not statistically significant difference in intracellular drug concentration between shRNA-XPG-733-SKOV3/DDP cell lines [(0.026 +/- 0.005) ug/ml] and shRNA-GAPDH [(0.024 +/- 0.003) ug/ml] and shRNA-NC cell lines [(0.025 +/- 0.007) ug/ml] after treated by cisplatin in vitro(P > 0.05, respectively). CONCLUSION: The down-regulating of XPG gene resulted in slowing growth velocity and descending the drug-resistance index of shRNA-XPG-733-SKOV3/DDP cell lines, which may be related with descending in capability of DNA excision repair in cells. PMID- 22781117 TI - [Effect of GPER on the activation of PI3K/Akt induced by 17beta-estradiol in endometrial carcinoma cells]. AB - OBJECTIVE: To investigate the expression of G protein-coupled ER (GPER) and ER in the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) induced by 17beta-estradiol (17beta-E(2))in endometrial carcinoma cells, Ishikawa and HEC-1A. METHODS: Expressions of GPER, ERalpha and ERbeta protein in Ishikawa and HEC-1A cells were detected by immunohistochemical SP method. Levels of GPER, ERalpha and ERbeta were examined by western blot in Ishikawa and HEC-1A cells after treated with 1*10(-6) mol/L 17beta-E(2) at different time (0, 15, 30, 60, 120 minutes). RESULTS: GPER was positive expressed in Ishikawa and HEC-1A cells. ERalpha and ERbeta were both positive expressed in Ishikawa cells. While, ERalpha was weakly expressed and ERbeta was almost negatively expressed in HEC-1A cells. Western blot analysis showed that 1*10(-6) mol/L 17beta-E(2) treatment, the Ishikawa and HEC-1A cells GPER protein level for 15 minutes markedly increased (P < 0.05), which Ishikawa 30 minutes, when cells reached the highest level (0.192 +/- 0.004), HEC-1A cells for 15 minutes and reached the highest level (0.184 +/- 0.006); Ishikawa and HEC-1A cells, Akt, activation of 15 minutes from the treatment start was significantly increased (P < 0.05), which Ishikawa cells for 30 minutes and reached the highest level (0.666 +/- 0.021), HEC-1A cells for 15 minutes and reached maximum (0.788 +/- 0.035); Ishikawa and HEC-1A cells, ERalpha and ERbeta protein expression did not change significantly (P > 0.05). CONCLUSION: GPER likely involved in non-nuclear activation of PI3K/Akt signaling pathways in endometrial carcinoma cells, Ishikawa and HEC-1A. PMID- 22781119 TI - Metformin and phenethyl isothiocyanate combined treatment in vitro is cytotoxic to ovarian cancer cultures. AB - BACKGROUND: High mortality rates in ovarian cancer are largely a result of resistance to currently used chemotherapies. Expanding therapies with a variety of drugs has the potential to reduce this high mortality rate. Metformin and phenethyl isothiocyanate (PEITC) are both potentially useful in ovarian cancer, and they are particularly attractive because of their safety. METHODS: Cell proliferation of each drug and drug combination was evaluated by hemacytometry with Trypan blue exclusion or Sytox green staining for cell death. Levels of total and cleaved PARP were measured by Western blot. General cellular and mitochondrial reactive oxygen species were measured by flow cytometry and live cell confocal microscopy with the fluorescent dyes dihydroethidine and MitoSOX. RESULTS: Individually, metformin and PEITC each show inhibition of cell growth in multiple ovarian cancer cell lines. Alone, PEITC was also able to induce apoptosis, whereas metformin was primarily growth inhibitory. Both total cellular and mitochondrial reactive oxygen species were increased when treated with either metformin or PEITC. The growth inhibitory effects of metformin were reversed by methyl succinate supplementation, suggesting complex I plays a role in metformin's anti-cancer mechanism. PEITC's anti-cancer effect was reversed by N acetyl-cysteine supplementation, suggesting PEITC relies on reactive oxygen species generation to induce apoptosis. Metformin and PEITC together showed a synergistic effect on ovarian cancer cell lines, including the cisplatin resistant A2780cis. CONCLUSIONS: Here we show that when used in combination, these drugs are effective in both slowing cancer cell growth and killing ovarian cancer cells in vitro. Furthermore, the combination of these drugs remains effective in cisplatin resistant cell lines. Novel combinations such as metformin and PEITC show promise in expanding ovarian cancer therapies and overcoming the high incidence of cisplatin resistant cancers. PMID- 22781120 TI - Porosity control in metal-assisted chemical etching of degenerately doped silicon nanowires. AB - We report the fabrication of degenerately doped silicon (Si) nanowires of different aspect ratios using a simple, low-cost and effective technique that involves metal-assisted chemical etching (MacEtch) combined with soft lithography or thermal dewetting metal patterning. We demonstrate sub-micron diameter Si nanowire arrays with aspect ratios as high as 180:1, and present the challenges in producing solid nanowires using MacEtch as the doping level increases in both p- and n-type Si. We report a systematic reduction in the porosity of these nanowires by adjusting the etching solution composition and temperature. We found that the porosity decreases from top to bottom along the axial direction and increases with etching time. With a MacEtch solution that has a high [HF]:[H(2)O(2)] ratio and low temperature, it is possible to form completely solid nanowires with aspect ratios of less than approximately 10:1. However, further etching to produce longer wires renders the top portion of the nanowires porous. PMID- 22781121 TI - A universal scaling relationship between body mass and proximal limb bone dimensions in quadrupedal terrestrial tetrapods. AB - BACKGROUND: Body size is intimately related to the physiology and ecology of an organism. Therefore, accurate and consistent body mass estimates are essential for inferring numerous aspects of paleobiology in extinct taxa, and investigating large-scale evolutionary and ecological patterns in the history of life. Scaling relationships between skeletal measurements and body mass in birds and mammals are commonly used to predict body mass in extinct members of these crown clades, but the applicability of these models for predicting mass in more distantly related stem taxa, such as non-avian dinosaurs and non-mammalian synapsids, has been criticized on biomechanical grounds. Here we test the major criticisms of scaling methods for estimating body mass using an extensive dataset of mammalian and non-avian reptilian species derived from individual skeletons with live weights. RESULTS: Significant differences in the limb scaling of mammals and reptiles are noted in comparisons of limb proportions and limb length to body mass. Remarkably, however, the relationship between proximal (stylopodial) limb bone circumference and body mass is highly conserved in extant terrestrial mammals and reptiles, in spite of their disparate limb postures, gaits, and phylogenetic histories. As a result, we are able to conclusively reject the main criticisms of scaling methods that question the applicability of a universal scaling equation for estimating body mass in distantly related taxa. CONCLUSIONS: The conserved nature of the relationship between stylopodial circumference and body mass suggests that the minimum diaphyseal circumference of the major weight bearing bones is only weakly influenced by the varied forces exerted on the limbs (that is, compression or torsion) and most strongly related to the mass of the animal. Our results, therefore, provide a much-needed, robust, phylogenetically corrected framework for accurate and consistent estimation of body mass in extinct terrestrial quadrupeds, which is important for a wide range of paleobiological studies (including growth rates, metabolism, and energetics) and meta-analyses of body size evolution. PMID- 22781122 TI - Of flies, mice and men: a systematic approach to understanding the early life origins of chronic lung disease. AB - Despite intensive research efforts, the aetiology of the majority of chronic lung diseases (CLD) in both, children and adults, remains elusive. Current therapeutic options are limited, providing only symptomatic relief, rather than treating the underlying condition, or preventing its development in the first place. Thus, there is a strong and unmet clinical need for the development of both, novel effective therapies and preventative strategies for CLD. Many studies suggest that modifications of prenatal and/or early postnatal lung development will have important implications for future lung function and risk of CLD throughout life. This view represents a fundamental change of current pathophysiological concepts and treatment paradigms, and holds the potential to develop novel preventative and/or therapeutic strategies. However, for the successful development of such approaches, key questions, such as a clear understanding of underlying mechanisms of impaired lung development, the identification and validation of relevant preclinical models to facilitate translational research, and the development of concepts for correction of aberrant development, all need to be solved. Accordingly, a European Science Foundation Exploratory Workshop was held where clinical, translational and basic research scientists from different disciplines met to discuss potential mechanisms of developmental origins of CLD, and to identify major knowledge gaps in order to delineate a roadmap for future integrative research. PMID- 22781123 TI - Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis. AB - BACKGROUND: Chronic respiratory disease and inhaled corticosteroid (ICS) therapy for chronic obstructive pulmonary disease (COPD) increase the risk of pneumonia. Few data are available on the association of these risk factors with non tuberculous mycobacterial (NTM) pulmonary disease. METHODS: This study examined chronic respiratory diseases and ICS use as risk factors in a population-based case-control study encompassing all adults in Denmark with microbiologically confirmed NTM pulmonary disease between 1997 and 2008. The study included 10 matched population controls per case. Conditional logistic regression was used to compute adjusted ORs for NTM pulmonary disease with regard to chronic respiratory disease history. RESULTS: Overall, chronic respiratory disease was associated with a 16.5-fold (95% CI 12.2 to 22.2) increased risk of NTM pulmonary disease. The adjusted OR for NTM disease was 15.7 (95% CI 11.4 to 21.5) for COPD, 7.8 (95% CI 5.2 to 11.6) for asthma, 9.8 (95% CI 2.03 to 52.8) for pneumoconiosis, 187.5 (95% CI 24.8 to 1417.4) for bronchiectasis, and 178.3 (95% CI 55.4 to 574.3) for tuberculosis history. ORs were 29.1 (95% CI 13.3 to 63.8) for patients with COPD on current ICS therapy and 7.6 (95% CI 3.4 to 16.8) for patients with COPD who had never received ICS therapy. Among patients with COPD, ORs increased according to ICS dose, from 28.1 for low-dose intake to 47.5 for high-dose intake (more than 800 MUg/day). The OR was higher for fluticasone than for budesonide. CONCLUSION: Chronic respiratory disease, particularly COPD treated with ICS therapy, is a strong risk factor for NTM pulmonary disease. PMID- 22781124 TI - Dementia in patients hospitalized with stroke: rates, time course, and clinico pathologic factors. AB - Stroke is a risk factor for dementia and dementia predisposes to stroke. Dementia prevalence in subjects with stroke is comparable with that seen in stroke-free subjects who are 10 years older. Although overall there is heterogeneity between studies of prestroke and poststroke dementia, stratifying by study method and clinical criteria (e.g. inclusion/exclusion of prestroke dementia, first ever vs. any vs. recurrent stroke) results in reasonably consistent estimates. Pooled dementia rates from studies of consecutive patients hospitalized with stroke indicate that around 10% have dementia prior to first stroke and 10% have new dementia in the first year after first-ever stroke with highest rates (over 30%) seen after recurrent stroke. After the immediate high-risk poststroke period, rates of new incident dementia are lower but remain elevated at around four times the background risk. Factors associated with prestroke and poststroke dementia are broadly similar but age, medial temporal lobe atrophy, female sex, and family history are more strongly associated with prestroke dementia suggesting a greater role for degenerative pathology. Poststroke dementia is associated with factors indicating a reduced cognitive reserve (prestroke cognitive decline, premorbid disability, low education, white matter disease, and atrophy) and is also strongly associated with stroke factors (lesion size, multiple lesions, and stroke recurrence) and complications of stroke (delirium, seizures, hypotension, systemic illness and incontinence) indicating the likely impact of optimal acute stroke care and secondary prevention in reducing the burden of dementia. Future studies are needed to clarify the interaction between degenerative, vascular, and systemic processes in the development of stroke-associated dementia. PMID- 22781125 TI - O-Mannose and O-N-acetyl galactosamine glycosylation of mammalian alpha dystroglycan is conserved in a region-specific manner. AB - Defects in the O-linked glycosylation of the peripheral membrane protein alpha dystroglycan (alpha-DG) are the main cause of several forms of congenital muscular dystrophies and thus the characterization of the glycosylation of alpha DG is of great medical importance. A detailed investigation of the glycosylation pattern of the native alpha-DG protein is essential for the understanding of the biological processes related to human disease in which the protein is involved. To date, several studies have reported novel O-glycans and attachment sites on the mucin-like domain of mammalian alpha-DG with both similar and contradicting glycosylation patterns, indicating the species-specific O-glycosylation of mammalian alpha-DG. By applying a standardized purification scheme and subsequent glycoproteomic analysis of native alpha-DG from rabbit and human skeletal muscle biopsies and from cultured mouse C2C12 myotubes, we show that the O-glycosylation patterns of the mucin-like domain of native alpha-DG are conserved among mammalians in a region-specific manner. PMID- 22781126 TI - Smoking and lung cancer-induced changes in N-glycosylation of blood serum proteins. AB - Glycosylation is a key post-translational protein modification which appears important in malignant transformation and tumor metastasis. Abnormal glycosylation of different proteins can often be measured in the blood serum. In this study, we extend our serum-based structural investigations to samples provided by patients diagnosed with lung cancer, paying particular attention to the effects of smoking on the serum glycomic traces. Following a battery of glycomic tests, we find that several fucosylated tetra-antennary structures with varying degrees of sialylation are increased in their abundances in control samples provided by the former smokers, with further elevations in the lung cancer patients who were former smokers. Further detailed investigations demonstrated that the level of outer-arm fucosylation was elevated in the control samples of the former smokers and again in the lung cancer samples provided by the former smokers. This trend was particularly noticeable for the tri- and tetra antennary structures. Different ratios of sialylation linkages were also observed that could be correlated with the different states of health and smoking status. Decreases in the abundance levels of isomers with two and three alpha2,3-linked sialic acids and an increased abundance of an isomer with two alpha2,6-linked sialic acids were noted for a fucosylated tri-sialylated tri-antennary glycan. These results demonstrate the long-term effects of smoking on glycomic profiles and that this factor needs to be considered in these and other serum-based analyses. PMID- 22781127 TI - The cis-regulatory code of Hox function in Drosophila. AB - Precise gene expression is a fundamental aspect of organismal function and depends on the combinatorial interplay of transcription factors (TFs) with cis regulatory DNA elements. While much is known about TF function in general, our understanding of their cell type-specific activities is still poor. To address how widely expressed transcriptional regulators modulate downstream gene activity with high cellular specificity, we have identified binding regions for the Hox TF Deformed (Dfd) in the Drosophila genome. Our analysis of architectural features within Hox cis-regulatory response elements (HREs) shows that HRE structure is essential for cell type-specific gene expression. We also find that Dfd and Ultrabithorax (Ubx), another Hox TF specifying different morphological traits, interact with non-overlapping regions in vivo, despite their similar DNA binding preferences. While Dfd and Ubx HREs exhibit comparable design principles, their motif compositions and motif-pair associations are distinct, explaining the highly selective interaction of these Hox proteins with the regulatory environment. Thus, our results uncover the regulatory code imprinted in Hox enhancers and elucidate the mechanisms underlying functional specificity of TFs in vivo. PMID- 22781128 TI - Phytochrome Kinase Substrate 4 is phosphorylated by the phototropin 1 photoreceptor. AB - Phototropism allows plants to redirect their growth towards the light to optimize photosynthesis under reduced light conditions. Phototropin 1 (phot1) is the primary low blue light-sensing receptor triggering phototropism in Arabidopsis. Light-induced autophosphorylation of phot1, an AGC-class protein kinase, constitutes an essential step for phototropism. However, apart from the receptor itself, substrates of phot1 kinase activity are less clearly established. Phototropism is also influenced by the cryptochromes and phytochromes photoreceptors that do not provide directional information but influence the process through incompletely characterized mechanisms. Here, we show that Phytochrome Kinase Substrate 4 (PKS4), a known element of phot1 signalling, is a substrate of phot1 kinase activity in vitro that is phosphorylated in a phot1 dependent manner in vivo. PKS4 phosphorylation is transient and regulated by a type 2-protein phosphatase. Moreover, phytochromes repress the accumulation of the light-induced phosphorylated form of PKS4 showing a convergence of photoreceptor activity on this signalling element. Our physiological analyses suggest that PKS4 phosphorylation is not essential for phototropism but is part of a negative feedback mechanism. PMID- 22781131 TI - C-type lectin-like proteins from snake venoms. AB - C-type lectin-like proteins (CTLs) as found in snake venoms fulfill various physiological functions. They play a role in hemostasis and have helped elucidate mechanisms involved in blood coagulation and platelet activation. Their basic structure consists of the subunits alpha and beta, which form heterodimers via a typical domain-swapping motif. These heterodimers can form oligomers such as the tetrameric flavocetin-A and convulxin, which arrange into cyclic structures. Rhodocetin is a selective alpha2beta1 integrin antagonist consisting of four distinct subunits forming a novel cruciform structure. Along with EMS16 and VP12, rhodocetin inhibits collagen-binding to the alpha2A-domain. These integrin specific antagonists are lead structures for the development of antimetastatic and antiangiogenic drugs. PMID- 22781129 TI - ARF6-mediated endosomal transport of Telencephalin affects dendritic filopodia-to spine maturation. AB - Dendritic filopodia are dynamic structures thought to be the precursors of spines during synapse development. Morphological maturation to spines is associated with the stabilization and strengthening of synapses, and can be altered in various neurological disorders. Telencephalin (TLN/intercellular adhesion molecule-5 (ICAM5)) localizes to dendritic filopodia, where it facilitates their formation/maintenance, thereby slowing spine morphogenesis. As spines are largely devoid of TLN, its exclusion from the filopodia surface appears to be required in this maturation process. Using HeLa cells and primary hippocampal neurons, we demonstrate that surface removal of TLN involves internalization events mediated by the small GTPase ADP-ribosylation factor 6 (ARF6), and its activator EFA6A. This endocytosis of TLN affects filopodia-to-spine transition, and requires Rac1 mediated dephosphorylation/release of actin-binding ERM proteins from TLN. At the somato-dendritic surface, TLN and EFA6A are confined to distinct, flotillin positive membrane subdomains. The co-distribution of TLN with this lipid raft marker also persists during its endosomal targeting to CD63-positive late endosomes. This suggests a specific microenvironment facilitating ARF6-mediated mobilization of TLN that contributes to promotion of dendritic spine development. PMID- 22781132 TI - Snake venom Lys49 myotoxins: From phospholipases A(2) to non-enzymatic membrane disruptors. AB - Snake venoms often contain toxins that cause a rapid necrosis of skeletal muscle fibers, referred to as myotoxins. The most common among them are phospholipases A(2) (PLA(2)s), enzymes that have two independent evolutionary origins in snake venoms. Within the group II PLA(2)s found in viperid venoms, a particular subgroup emerged, in which the otherwise conserved Asp49 of their catalytic center is replaced by Lys49. These intriguing proteins, referred to as Lys49 myotoxins, lost the ability to catalyze phospholipid hydrolysis, but still induce myonecrosis by a non-enzymatic mechanism based on membrane permeabilization as the critical event. Such mechanism is only partially understood. This review briefly describes the general structural and functional characteristics of the Lys49 myotoxins, and summarizes four proposed models of their functional "toxic site". Finally, it discusses some novel insights into their mode of action, in particular examining arguments and experimental observations that could shed light on the possible nature of their membrane target on skeletal muscle cells, which remains elusive. PMID- 22781133 TI - Effect of HUVEC apoptosis inducing proteinase from Vipera lebetina venom (VLAIP) on viability of cancer cells and on platelet aggregation. AB - Three cancer cell lines, the human androgen independent prostate cancer PC-3, androgen dependent LNCaP prostate cancer and human chronic myeloid leukaemia cell line K-562, were treated with Sephadex G-100 sf fractions of Vipera lebetina venom and with HUVEC apoptosis inducing heterodimeric metalloproteinase (VLAIP) from the same venom. The venom was separated into nine fractions using size exclusion chromatography on Sephadex G-100 sf. The effect of V. lebetina venom gel filtration fractions on the viability of studied cancer cells was different: high molecular mass fractions were the most effective on PC-3 cells. The viability of LNCaP cells was inhibited most strongly by the third fraction. The first and the second fractions contain different metalloproteinases including VLAIP that also most effectively reduced the viability of PC-3 cells. VLAIP decreased PC-3 cell viability in a concentration- and time-dependent manner but did not induce apoptosis as shown by DNA fragmentation assay. VLAIP induced changes in cell shape, rounding up and detachment. VLAIP inhibited the PC-3 cell adhesion to extracellular matrix proteins collagen I, fibronectin and vitronectin but not to fibrinogen. VLAIP had no significant effect on the viability of LNCaP and K-562 cells. VLAIP was also capable to inhibit ADP- and collagen-induced platelet aggregation dose-dependently. IC(50) was determined to be 1.89 MUM and 0.94 MUM, respectively. PMID- 22781134 TI - Improving antivenom availability and accessibility: science, technology, and beyond. AB - Snakebite envenomings constitute a serious and neglected public health problem. Despite the fact that effective treatment exists, i.e. administration of animal derived antivenoms, the availability and accessibility of these life-saving immunobiologicals is deficitary in various parts of the world, particularly in sub-Saharan Africa and some regions of Asia. This article discusses some of the problems that need to be circumvented in order to improve the availability and accessibility of antivenoms. The conglomerate of antivenom manufacturers is highly heterogeneous in terms of technological base, qualification of staff, implementation of Good Manufacturing Practices (GMPs), and volume of production. Therefore, improvements in antivenom quality and availability should be based on strategies tailored to the situation of each region or country; in this context, three different scenarios are discussed. Accessibility of antivenoms demands concerted efforts at multiple levels, including raising the awareness of public health authorities on the relevance of the problem, implementing innovative antivenom purchasing schemes, strengthening national distribution channels on the basis of robust epidemiological information, improving the cold chain and the provision of health services in remote rural settings, supporting the correct use of antivenoms, and promoting the involvement of local community organizations in various aspects of prevention and management. These tasks should be envisaged in terms of synergistic, interprogrammatic and intersectorial interventions, with the participation of many players. PMID- 22781135 TI - An indirect approach for anion detection: the displacement strategy and its application. AB - The development of new optical anion chemosensors with high sensitivity and selectivity is very important, since anions possess some fundamental roles in a wide range of biological and chemical processes. The displacement approach is a method using anion binding sites and signaling subunits, which are not covalently attached but forming a coordination complex, in which the presence of anions revives the noncoordinated spectroscopic behavior of the indicator. In the past five years, according to the displacement strategy, many good optical anion chemosensors have been successfully obtained. This paper reviews the recent progress in the field of the fluorescent and colorimetric anion chemosensors designed according to the displacement strategy (mainly from 2008 to 2011), and gives some outlooks for the further exploration of new optical anion chemosensors. PMID- 22781136 TI - Effect of single-set resistance training on quality of life in COPD patients enrolled in pulmonary rehabilitation. AB - BACKGROUND: Single-set resistance training (SSRT) improves strength and function in older adults with COPD. However, its effect on quality of life (QOL) has not been evaluated. This study evaluated the effect of SSRT on QOL in COPD patients enrolled in pulmonary rehabilitation (PR) and identified relationships between muscular strength, endurance and QOL. METHODS: Nineteen men and women (70.5 +/- 5.0 years old) with COPD completed 8 weeks of PR alone or PR plus SSRT. QOL was measured using the Medical Outcomes Study Short Form 36. Upper and lower body strength was measured using chest and leg press, and lower body endurance was measured with the 6-min walk test. RESULTS: There were no significant differences in QOL between PR with versus without SSRT before or after PR. Both groups demonstrated significant improvements in QOL, including the Physical Function (P = .02), Role Physical (P = .002), Vitality (P = .03), Social Functioning (P = .03), and Mental Health (P = .04) domains. Before PR, only lower body strength and endurance were significantly related to Physical Function (r = 0.53, P = .02 and r = 0.51, P = .03, respectively). After the exercise program, upper body strength as well as lower body strength and endurance were significantly related to Physical Function (r = 0.57, P = .01, r = 0.51, P = .03, and r = 0.62, P = .005, respectively), although improvements in Physical Function were predicted solely by improvements in upper body strength (r = 0.54, P = .02). CONCLUSIONS: The addition of SSRT to traditional PR does not affect overall improvements in QOL that are influenced primarily by an increase in upper body strength. Our findings suggest a threshold effect for exercise training, such that, once a threshold stimulus has been achieved, further improvements in QOL are not dose dependent. PMID- 22781137 TI - In vitro anti-Toxoplasma gondii activity of root extract/fractions of Eurycoma longifolia Jack. AB - BACKGROUND: Toxoplasma gondii infection causes toxoplasmosis, an infectious disease with worldwide prevalence. The limited efficiency of drugs against this infection, their side effects and the potential appearance of resistant strains make the search of novel drugs an essential need. We examined Eurycoma longifolia root extract and fractions as potential sources of new compounds with high activity and low toxicity. The main goal of this study was to investigate the anti-T. gondii activity of crude extract (TACME) and four fractions (TAF 273, TAF 355, TAF 191 and TAF 401) from E. longifolia, with clindamycin as the positive control. METHODS: In vitro toxoplasmacidal evaluation was performed using Vero cells as host for T. gondii. Light microscopy technique was used to study in situ antiparasitic activity. RESULTS: Significant anti-T. gondii activity was observed with clindamycin (EC50 = 0.016 MUg/ml), follow by TAF 355 (EC50 = 0.369 MUg/ml) and TAF 401 (EC50 = 0.882 MUg/ml). Light microscopy revealed that most Vero cells were infected after 3 h of exposure to T. gondii. After 36 h of exposure to the E. longifolia fraction, the host Vero cells showed no visible intracellular parasite and no remarkable morphological changes. CONCLUSIONS: Our study demonstrated that TAF 355 and TAF401 fractions may be the sources of new anti-T. gondii compounds. PMID- 22781138 TI - Dermatologic manifestations of endocrine disorders. AB - PURPOSE OF REVIEW: The diagnosis of many childhood endocrine disorders can be facilitated by an awareness of the associated dermatologic findings. In this review, we will survey examples of endocrine disorders in children that include a prominent or diagnostic dermatologic sign/symptom. RECENT FINDINGS: A key concept is that skin findings often accompany hormonal conditions, both those of hormone excess and hormone deficiency/resistance. Some dermatologic signs may also represent the hallmark lesion, or provide the first clinical sign in childhood, for both familial tumoral and nontumoral syndromes. Moreover, skin as an endocrine organ itself may provide new avenues both to understand disease mechanisms as well as to provide targeted therapy. SUMMARY: Early diagnosis, often aided by recognition of a keynote dermatologic lesion, may permit prompt, timely treatment that, in some cases, may even prove life saving. Conversely, when these associated signs go undetected or misdiagnosed, therapeutic intervention may be delayed unnecessarily. PMID- 22781139 TI - Clostridium difficile infection and proton pump inhibitors. AB - PURPOSE OF REVIEW: Clostridium difficile is an intestinal infection associated with antibiotic use, commonly seen in patients with chronic medical issues. The purpose of this review is to discuss the association of C. difficile-associated diarrhea with use of proton pump inhibitors. RECENT FINDINGS: Multiple medical factors predispose patients to C. difficile-associated diarrhea. Proton pump inhibitors, commonly used for gastric acid suppression, have been shown to have an association with C. difficile-associated diarrhea in both the outpatient and hospital setting. C. difficile-associated diarrhea also has been reported in the pediatric age range linked with proton pump inhibitor use. SUMMARY: An association exists between C. difficile infection and proton pump inhibitor use. Treatment options exist for C. difficile-associated diarrhea, although judicious use of proton pump inhibitors and antibiotics, emphasis on hand washing, and appropriate use of patient isolation should be implemented as well. PMID- 22781140 TI - Environmental enrichment restores cognitive deficits induced by prenatal maternal seizure. AB - Maternal seizure has adverse effects on brain histology as well as on learning and memory ability in progeny. An enriched environment (EE) is known to promote structural changes in the brain and improve cognitive and motor deficits following a variety of brain injuries. Whether EE treatment in early postnatal periods could restore cognitive impairment induced by prenatal maternal seizure is unknown. Adult female Sprague-Dawley rats were randomly separated into two groups and were injected intraperitoneally either saline or pentylenetetrazol (PTZ) for 30 days. Then the fully kindled rats and control animals were allowed to mate. PTZ administration was continued until delivery, while the control group received saline at the same time. After weaning at postnatal day 22, one-half of the male offspring in the control and in the prenatal maternal group were given the environmental enrichment treatment through all the experiments until they were tested. Morris water maze testing was performed at 8 weeks of age. Western blot and synaptic ultrastructure analysis were then performed. We found that EE treatment reversed spatial learning deficits induced by prenatal maternal seizure. An EE also reversed the changes in synaptic ultrastructure following prenatal maternal seizure. In addition, prenatal maternal seizure significantly decreased phosphorylation states of cAMP response element binding (CREB) in the hippocampus, whereas EE reversed this reduced expression. These findings suggest that EE treatment on early postnatal periods could be a potential therapy for improving cognitive deficits induced by prenatal maternal seizure. PMID- 22781142 TI - Neuronal degeneration and gliosis time-course in the mouse hippocampal formation after pilocarpine-induced status epilepticus. AB - Temporal lobe epilepsy (TLE) is the most common type of human epilepsy and has been related with extensive loss of hippocampal pyramidal and dentate hilar neurons and gliosis. Many characteristics of TLE are reproduced in the pilocarpine model of epilepsy in mice. This study analyzed the neuronal damage, assessed with Fluoro-Jade (FJB) and cresyl violet, and gliosis, investigated with glial fibrilary acidic protein (GFAP) immunohistochemistry, occurring in the hippocampal formation of mice at 3, 6, 12 and 24h, 1 and 3 weeks after the pilocarpine-induced status-epilepticus (SE) onset. The maximum neuronal damage score and the FJB-positive neurons peak were found in the hilus of dentate gyrus 3 and 12 h after SE onset (P<0.05), respectively. At 1 week after SE onset, the greatest neuronal damage score was detected in the CA1 pyramidal cell layer and the greatest numbers of FJB-positive neurons were found both in the CA1 and CA3 pyramidal cell layers (P<0.05). The molecular, CA3 and CA1 pyramidal cell layers expressed highest presence of GFAP immunoreaction at 1 and 3 weeks after SE onset (P<0.05). Our findings show that, depending on the affected area, neuronal death and gliosis can occur within few hours or weeks after SE onset. Our results corroborate previous studies and characterize short time points of temporal evolution of neuropathological changes after the onset of pilocarpine-induced SE in mice and evidences that additional studies of this temporal evolution may be useful to the comprehension of the cellular mechanisms underlying epileptogenesis. PMID- 22781141 TI - Perfluorocarbon-facilitated CNS oxygen toxicity in rats: reversal by edaravone. AB - Perfluorocarbon (PFC) has been hypothesized to potentially increase the risk of central nervous system oxygen toxicity (CNS-OT) under hyperbaric oxygen (HBO) conditions. However, little is known about the effects, mechanism and prevention of PFC-facilitated CNS-OT. A rat model of CNS-OT was used to evaluate the effects of intravenously-administered PFC emulsion. The electroencephalogram (EEG) was recorded during treatment with HBO(2) at 6.0 ATA in the presence and absence of PFC. Concentrations of malondialdehyde (MDA), nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) in the brain cortex and hippocampus were quantified. Changes in the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and NO synthase (NOS) in the brain cortex and hippocampus were also determined. Edaravone, a potent antioxidant, was used to prevent PFC facilitated CNS-OT. The results showed that after PFC administration, the latency to first electrical discharge in EEG was significantly shortened; MDA, H(2)O(2), NO levels and NOS activity increased; and SOD, GPx and CAT activities decreased. Edaravone effectively protected against CNS-OT and the adverse effects of PFC. The results clearly demonstrate that PFC administered before HBO(2) would promote the occurrence of CNS-OT, and edaravone could serve as a promising chemoprophylactic agent to prevent CNS-OT. PMID- 22781143 TI - Methionine-enriched diet decreases hippocampal antioxidant defences and impairs spontaneous behaviour and long-term potentiation in rats. AB - Diets high in methionine lead to elevation of plasma homocysteine levels which are possibly linked to neurodegenerative diseases and oxidative stress. In the present study, we investigated the effects of methionine-enriched diet on antioxidant defences, on rat spontaneous behaviour and on the ability to sustain long-term potentiation in the dentate gyrus (DG). Sprague-Dawley rats were fed either a standard laboratory diet or a methionine enriched-diet (1% or 5% methionine in drinking water) for 8 weeks. After the 8 weeks, the animals were tested for spontaneous motor activity and habituation in an open field maze, for anxiety-like behaviour in an elevated plus maze and for the ability to sustain long-term potentiation (LTP) induced in the dentate gyrus under urethane anaesthesia. The brains were then removed and histochemically stained for superoxide dismutase (SOD) activity. Rats fed on 5% methionine significantly reduced total distance travelled during the open field test and exhibited no habituation with respect to the other two groups. Rats fed on 5% methionine also showed a significant increase of the anxiety level. Moreover, in this group, the ability to induce LTP in DG was impaired. SOD activity was significantly increased in the cerebral cortex of the rats fed on 1% and 5% methionine with respect to the control group. In conclusion, 5% methionine in drinking water led to evident impairment of locomotor skills and of synaptic plasticity. SOD activity in the cortex was increased in both the groups fed on 1% and 5% methionine, thus suggesting that metabolic adjustments, triggered by the methionine-enriched diet, are likely mediated by reactive oxygen species. PMID- 22781144 TI - Extraction of chromium, copper, and arsenic from CCA-treated wood by using wood vinegar. AB - In the present study, wood vinegar was used to extract chromium, copper, and arsenic from chromated copper arsenate (CCA)-treated wood. The extraction efficiency for CCA elements was evaluated using various concentrations of wood vinegar, extraction temperatures, and extraction periods. The extraction efficiency for CCA elements increased with increasing the concentration of wood vinegar and the extraction conditions, resulting in maximal removal rate of copper (95.7%), followed by arsenic (92.7%) and chromium (86.3%). Since wood vinegar afforded high levels of copper extraction, its use was extended to copper based preservative-treated wood, wherein significant extraction of copper up to 97.6% and 95.7% was obtained from alkaline copper quats (ACQ)- and copper azole (CuAz)-treated sawdust, respectively. To the best of our knowledge, this is the first study on the application of wood vinegar for the extraction of metal elements from CCA-treated wood. PMID- 22781145 TI - Sub-100 nm Si nanowire and nano-sheet array formation by MacEtch using a non lithographic InAs nanowire mask. AB - We report a non-lithographical method for the fabrication of ultra-thin silicon (Si) nanowire (NW) and nano-sheet arrays through metal-assisted-chemical-etching (MacEtch) with gold (Au). The mask used for metal patterning is a vertical InAs NW array grown on a Si substrate via catalyst-free, strain-induced, one dimensional heteroepitaxy. Depending on the Au evaporation angle, the shape and size of the InAs NWs are transferred to Si by Au-MacEtch as is (NWs) or in its projection (nano-sheets). The Si NWs formed have diameters in the range of ~25-95 nm, and aspect ratios as high as 250 in only 5 min etch time. The formation process is entirely free of organic chemicals, ensuring pristine Au-Si interfaces, which is one of the most critical requirements for high yield and reproducible MacEtch. PMID- 22781146 TI - [A study on the correlation between exercise-induced bronchoconstriction and atopy]. AB - OBJECTIVE: To investigate the correlation between exercise-induced bronchoconstriction and atopy. METHODS: Exercise-induced bronchoconstriction (EIB) was defined by free running asthma screening test. Atopy was defined by serum total IgE level and skin allergen test. Airway hyperreactivity was determined by bronchial provocation test. For a matched pair study, all EIB and some non-EIB students received serum total IgE measurements, skin allergen test and bronchial provocation test. All data were calculated by correlation analysis to investigate the correlation between EIB and atopy. RESULTS: Totally 773 students participated in the free running screening test, and 89 students (11.5%) were diagnosed as having EIB. The serum total IgE level exceeded the normal range in 16 among the 89 EIB students, but in 10 among the 70 non-EIB students. Statistical analysis (chi(2) test) did not support the correlation between atopy and EIB. Fifty EIB students received bronchial provocation test, but only 1 showed airway hyperreactivity. CONCLUSION: There was no correlation between atopy and EIB, and airway hyperreactivity was absent in most of the EIB students. PMID- 22781147 TI - [The diagnostic value of CT-guided percutaneous needle lung biopsy in diffuse parenchymal lung diseases]. AB - OBJECTIVE: This study was to evaluate the efficacy and limitation of CT-guided percutaneous cutting needle lung biopsy in the diagnosis of diffuse parenchymal lung diseases (DPLD). METHODS: A total of 481 patients admitted in Peking Union Medical College Hospital from January 2000 to December 2008 underwent CT-guided percutaneous cutting needle lung biopsy. The patients were evaluated by clinical history, physical examination and lung HRCT. Those with localized opacity or lesions in a single lung in the CT scan were excluded. Finally, 248 patients with DPLD in HRCT were enrolled for this study. RESULTS: The study patients included 114 males and 134 females, and the mean (+/- SD) age at diagnosis was 50 +/- 16 (range from 13 - 78) years. Confirmed diagnosis by percutaneous needle lung biopsy was obtained in 130 patients (52.4%), including pulmonary infection (35.4%, 46/130), pulmonary malignant diseases (25.4%, 33/130), bronchiolitis obliterans organizing pneumonia/organizing pneumonia (22.3%, 29/130), pulmonary vasculitis (6.2%, 8/130), granulomatous lesions (4.6%, 6/130), pulmonary sarcoidosis (2.3%, 3/130), acute interstitial pneumonia (1.5%, 2/130), pulmonary amyloidosis (1.5%, 2/130), and pulmonary alveolar proteinosis (0.8%, 1/130). Open lung biopsy/video-assisted thoracoscopic surgery was performed in 37 out of 118 cases for which the diagnosis was undetermined by percutaneous lung biopsy. Confirmed diagnosis was obtained in 36 patients, including non-specific interstitial pneumonia (NSIP, 33.3%, 12/36), usual interstitial pneumonia (UIP, 8.3%, 3/36), pulmonary infection (16.7%, 6/36), neoplasm (8.3%, 3/36), lymphoid interstitial pneumonia, pulmonary vasculitis (5.6% 2/36), hypersensitivity pneumonitis (5.6%, 2/36), and pulmonary sarcoidosis, allergic bronchopulmonary aspergillosis, pulmonary hyalinizing granuloma, pneumoconiosis, Castleman's disease, and lymphoproliferative disorder (1 case respectively). CONCLUSION: CT guided percutaneous cutting needle lung biopsy can provide confirmed diagnosis in half of patients with DPLD, and has a high diagnostic yield in patients with infectious or neoplastic diseases, but it is not a good method for diagnosis of interstitial lung diseases such as NSIP and UIP. PMID- 22781148 TI - [Endobronchial lipoma: report of 2 cases and review of the Chinese literature]. AB - OBJECTIVE: To describe the epidemiology of endobronchial lipoma and to propose appropriate diagnostic and therapeutic policies for this tumor. METHODS: Two cases of endobronchial lipoma were presented and 38 cases reported in literatures published in mainland China were reviewed. RESULTS: Thirty-one male and 9 female patients were included, with a mean age of (53 +/- 11) years. The overwhelming majority of the tumors (n = 37) were found in the trachea, left or right main bronchi and lobular bronchi. The main symptoms included cough, dyspnea, fever and hemoptysis. Chest CT showed fat or soft tissue density endobronchial masses in 75% (21/28) cases. Eight patients (22.2%) were diagnosed by histological study of the transbronchial biopsy specimen. Thirty-two patients underwent surgical resection. Bronchoscopic resection was carried out in 7 cases. CONCLUSION: CT and bronchoscope are highly useful diagnostic tools for endobronchial lipoma. Bronchoscopic resection should be considered as the first choice of treatment for endobronchial lipoma. PMID- 22781149 TI - [Obstructive sleep apnea-hypopnea syndrome in patients with pulmonary thromboembolism: clinical features and management]. AB - OBJECTIVE: To describe the clinical features of obstructive sleep apnea-hypopnea syndrome (OSAHS) in hospitalized pulmonary thromboembolism (PTE) patients, and to explore its impact on the severity of disease and management among patients with PTE. METHODS: Demographic and clinical characteristics of 28 PTE patients complicated with OSAHS admitted to this hospital from January 2002 to December 2010 were analyzed. A total of 30 PTE patients without OSAHS served as a control group. RESULTS: PTE patients with OSAHS had a significantly lower age of onset of disease [(55 +/- 11) yr vs (66 +/- 11) yr, t = 3.230, P < 0.01], an increased body mass index (BMI) [(30.1 +/- 2.8) kg/m(2) vs (26.1 +/- 3.1) kg/m(2), t = 4.161, P < 0.001] and a higher smoking index [(19 +/- 6) packs/yr vs (8 +/- 4) packs/yr, t = -1.713, P < 0.05] when compared with PTE patients without OSAHS. PaO2 [(70 +/- 8) mm Hg vs (79 +/- 6) mm Hg, 1 mm Hg = 0.133 kPa, t = 4.233, P < 0.05] and involved lung segments [(8 +/- 4) vs (5 +/- 3), t = -2.496, P < 0.05] in PTE patients with OSAHS were more severe than those in PTE patients without OSAHS. All patients received anticoagulation and/or thrombolysis treatment, and continuous positive airway pressure (CPAP) ventilation was used in some PTE patients with OSAHS. CONCLUSION: PTE patients with OSAHS had a significantly earlier age of onset of disease and more severe conditions than PTE patients without OSAHS. Treatments including anticoagulation and CPAP should be used in these patients. PMID- 22781150 TI - [Characteristics of extrapulmonary tuberculosis in (18)F-2-fluoro-2-deoxy-D glucose positron emission tomography-computed tomography: experience from 39 cases]. AB - OBJECTIVE: The clinical manifestations and the imaging features in (18)F-2-fluoro 2-deoxy-D-glucose positron emission tomography ((18)F-FDG PET) of extrapulmonary tuberculosis were not specific and therefore it was difficult to be differentiated from malignancy. This paper tried to analyze the clinical characteristics and findings by (18)F-FDG PET-CT in extrapulmonary tuberculosis, in order to improve the diagnosis of this disease. METHODS: Thirty-nine patients with extrapulmonary tuberculosis underwent (18)F-FDG PET-CT imaging from 2003 - 2011. The diagnosis was confirmed by histopathological examination in all the cases. There were 11 males and 28 females, aging 20 - 67 (60 +/- 18) years. A past history of tuberculosis was collected in 5 cases. The PET images were reviewed visually and scored semi-quantitatively with standardized uptake value. The lesions were judged by PET imaging features in conjunction with CT slices and the fused images. RESULTS: Fever was present in 13 cases, and night sweating, weakness and malaise in 17 cases. Pleural effusion was found in 7 cases. Abdominal distention and masses were found in 6 cases, while neck mass was present in 2 cases. Laboratory tests showed that hypoalbuminemia, sedimentation rate increase and positive tuberculin tests were present in 15 cases. CA125 was increased in 3 cases. In PET-CT, lymph node tuberculosis manifested as single or multiple enlarged lymph nodes coalesced and calcified with significant FDG uptake, but ring-like FDG-avidity was also found in some of the lymph nodes. Pleural or peritoneal tuberculosis showed heterogeneous or nodular thickening and in a radio-tracer distribution. Bone tuberculosis manifested as osteolytic osseous destruction and paravertebral cold abscess, while focal radio-agent ring like intense uptake was present in half the cases. In patients with intestinal tuberculosis, ileocecal circumferential or eccentric thickening was observed, with focal or diffuse high FDG activity. Tuberculosis in adrenal gland, liver, and oviducts all showed lesions with high FDG uptake. CONCLUSIONS: (18)F-FDG PET CT was helpful for the differential diagnosis of extrapulmonary tuberculosis from malignancy. Osseous and lymph node tuberculosis showed ring-like FDG uptake, which maybe of diagnostic value. PMID- 22781152 TI - [cDNA library constructing and specific antigen expression of Streptomyces thermohydroscopicus]. AB - OBJECTIVE: To construct a cDNA library from Streptomyces thermohydroscopicus and screen genes with virulence, obtain the recombinant fusion virulence proteins by prokaryotic expression system. METHODS: The Streptomyces thermohydroscopicus cDNA library was constructed by switching mechanism at 5'end of RNA transcript approach. A total of 1020 clones randomly selected from the cDNA library were sequenced and these expressed sequence tags (EST) were further analyzed for the screen of antigen-specific genes. The two candidate genes were subcloned into expression vector pET-28a. The recombinants were transformed into BL2 and proteins were expressed by the induction of isopropyl-beta-D-1 thiogalactopyranoside (IPTG). RESULTS: A high-quality cDNA library from Streptomyces thermohydroscopicus was constructed and a set of 978 valid sequences were obtained. Clustering and assembly of these cDNA sequences resulted in 347 unique genes, among which 2 potential antigen-specific genes were highly allied with outer membrane lipoprotein (51%) and transferring-binding protein B (42%) from Actinobacillus pleuropneumoniae serotype (APP). The open reading frame (ORF) of the two candidate genes are 1554 bp and 726 bp, which coded two peptides with 517 and 241 amino acids, respectively. The molecular weights of the recombinant fusion proteins were 63 000 and 30 000. CONCLUSION: The cDNA library of Streptomyces thermohydroscopicus reached the quality requirement of gene library. EST database in the library would greatly facilitate further screening of virulence genes. PMID- 22781151 TI - [Hepatic injury in rats exposed to chronic intermittent hypoxia and the effect of tempol]. AB - OBJECTIVE: To investigate the mechanism of liver injury in rats exposed to chronic intermittent hypoxia (CIH) and to investigate the effect of tempol (4 hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl or 4-hydroxy-TEMPO). METHODS: A CIH animal model of rats was established to mimic the intermittent hypoxia/re oxygenation (IH/ROX) of obstructive sleep apnea syndrome in humans. Thirty-two healthy male Wistar rats were randomly assigned to 4 groups: conventional intermittent hypoxia group (CIH group), intermittent hypoxia Tempol treatment group (CIH + T group), intermittent hypoxia normal saline matched group (CIH + NS group), and normoxic control group (NC group), with 8 rats in each group. The frequency of every CIH group was 30 times/h, and the minimum oxygen concentration was 5%. After the experiment, sections of liver were stained with hematoxylin eosin (HE) and the levels of nuclear factor-kappaB (NF-kappaB), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) in rat liver homogenate were measured. RESULTS: Liver histology revealed that the CIH group and the CIH + NS group showed hepatocellular swelling with rarefaction of the cytoplasm, hyperchromatosis and hepatocellular membrane disruption, but the liver histology of the CIH + T group and the NC group was normal. Compared with the NC group, the levels of NF-kappaB and MDA in the CIH group [(12.4 +/- 2.0) ng/g, (101 +/- 22) umol/g] and the CIH + NS group [(12.2 +/- 1.9) ng/g, (99 +/- 18)umol/g] were increased (all P < 0.05), but the activities of GSH-PX [(88 +/- 17) U/mg, (90 +/- 15) U/mg] were decreased (all P < 0.05). Compared with the CIH + NS group and the CIH group, the activity of GSH-PX in the CIH + T group [(181 +/- 29) U/mg] was increased (P < 0.05), but the levels of NF-kappaB [(7.8 +/- 1.3) ng/g] and MDA [(59 +/- 10) umol/g] were decreased (all P < 0.05). The levels of GSH-PX and MDA in the CIH + T group were not significantly different compared to the NC group (P were 0.242, 0.177 respectively), but the level of NF-kappaB in the CIH + T group was higher than that in the NC group (P < 0.05). The levels of NF-kappaB, GSH-PX, and MDA in the CIH + NS group were not significantly different as compared to those in the CIH group (all P > 0.05). The level of NF-kappaB was correlated negatively with GSH-PX, but positively with MDA (r = -0.754, 0.689, respectively, all P < 0.01) CONCLUSIONS: CIH could cause rat liver injury through oxidative stress and activating the proinflammatory transcription factors of NF-kappaB. Tempol could prevent CIH-induced liver injury through scavenging ROS by its anti oxidative effect. PMID- 22781153 TI - [The value of omazulimab in the treatment of severe asthma]. PMID- 22781154 TI - [Heart rate variability in chronic obstructive pulmonary disease]. PMID- 22781155 TI - [Endothelial dysfunction and oxidative stress induced by chronic intermittent hypoxia]. PMID- 22781156 TI - [The role of autophagy in the immune response of tuberculosis]. PMID- 22781157 TI - [Advances in the research of rapid detection methods of pyrazinamide-resistant Mycobacterium tuberculosis]. PMID- 22781158 TI - Genetics of type 2 diabetes in European populations. AB - Type 2 diabetes (T2D) has become a leading health problem throughout the world. It is caused by environmental and genetic factors, as well as interactions between the two. However, until very recently, the T2D susceptibility genes have been poorly understood. During the past 5 years, with the advent of genome-wide association studies (GWAS), a total of 58 T2D susceptibility loci have been associated with T2D risk at a genome-wide significance level (P < 5 * 10(-8) ), with evidence showing that most of these genetic variants influence pancreatic beta-cell function. Most novel T2D susceptibility loci were identified through GWAS in European populations and later confirmed in other ethnic groups. Although the recent discovery of novel T2D susceptibility loci has contributed substantially to our understanding of the pathophysiology of the disease, the clinical utility of these loci in disease prediction and prognosis is limited. More studies using multi-ethnic meta-analysis, gene-environment interaction analysis, sequencing analysis, epigenetic analysis, and functional experiments are needed to identify new susceptibility T2D loci and causal variants, and to establish biological mechanisms. PMID- 22781159 TI - The clinical consequences of a pre-hospital diagnosis of stroke by the emergency medical service system. A pilot study. AB - BACKGROUND: There is still a considerable delay between the onset of symptoms and arrival at a stroke unit for most patients with acute stroke.The aim of the study was to describe the feasibility of a pre-hospital diagnosis of stroke by an emergency medical service (EMS) nurse in terms of diagnostic accuracy and delay from dialing 112 until arrival at a stroke unit. METHODS: Between September 2008 and November 2009, a subset of patients with presumed acute stroke in the pre hospital setting were admitted by EMS staff directly to a stroke unit, bypassing the emergency department. A control group, matched for a number of background variables, was created. RESULTS: In all, there were 53 patients in the direct admission group, and 49 patients in the control group. The median delay from calling for an ambulance until arrival at a stroke unit was 54 minutes in the direct admission group and 289 minutes in the control group (p < 0.0001).In a comparison between the direct admission group and the control group, a final diagnosis of stroke, transient ischemic attack (TIA) or the sequelae of prior stroke was found in 85% versus 90% (NS). Among stroke patients who lived at home prior to the event, the percentage of patients that were living at home after 3 months was 71% and 62% respectively (NS). CONCLUSIONS: In a pilot study, the concept of a pre-hospital diagnosis of stroke by an EMS nurse was associated with relatively high diagnostic accuracy in terms of stroke-related diagnoses and a short delay to arrival at a stroke unit. These data need to be confirmed in larger studies, with a concomitant evaluation of the clinical consequences and, if possible, the level of patient satisfaction as well. PMID- 22781160 TI - A cluster randomized trial to assess the effect of clinical pathways for patients with stroke: results of the clinical pathways for effective and appropriate care study. AB - BACKGROUND: Clinical pathways (CPs) are used to improve the outcomes of acute stroke, but their use in stroke care is questionable, because the evidence on their effectiveness is still inconclusive. The objective of this study was to evaluate whether CPs improve the outcomes and the quality of care provided to patients after acute ischemic stroke. METHODS: This was a multicentre cluster randomized trial, in which 14 hospitals were randomized to the CP arm or to the non intervention/usual care (UC) arm. Healthcare workers in the CP arm received 3 days of training in quality improvement of CPs and in use of a standardized package including information on evidence-based key interventions and indicators. Healthcare workers in the usual-care arm followed their standard procedures. The teams in the CP arm developed their CPs over a 6-month period. The primary end point was mortality. Secondary end points were: use of diagnostic and therapeutic procedures, implementation of organized care, length of stay, re-admission and institutionalization rates after discharge, dependency levels, and complication rates. RESULTS: Compared with the patients in the UC arm, the patients in the CP arm had a significantly lower risk of mortality at 7 days (OR = 0.10; 95% CI 0.01 to 0.95) and significantly lower rates of adverse functional outcomes, expressed as the odds of not returning to pre-stroke functioning in their daily life (OR = 0.42; 95 CI 0.18 to 0.98). There was no significant effect on 30-day mortality. Compared with the UC arm, the hospital diagnostic and therapeutic procedures were performed more appropriately in the CP arm, and the evidence-based key interventions and organized care were more applied in the CP arm. CONCLUSIONS: CPs can significantly improve the outcomes of patients with ischemic patients with stroke, indicating better application of evidence-based key interventions and of diagnostic and therapeutic procedures. This study tested a new hypothesis and provided evidence on how CPs can work. TRIAL REGISTRATION: ClinicalTrials.gov ID: [NCT00673491]. PMID- 22781161 TI - Effects of emotional context on impulse control. AB - High risk behaviors such as narcotic use or physical fighting can be caused by impulsive decision making in emotionally-charged situations. Improved neuroscientific understanding of how emotional context interacts with the control of impulsive behaviors may lead to advances in public policy and/or treatment approaches for high risk groups, including some high-risk adolescents or adults with poor impulse control. Inferior frontal gyrus (IFG) is an important contributor to response inhibition (behavioral impulse control). IFG also has a role in processing emotional stimuli and regulating emotional responses. The mechanism(s) whereby response inhibition processes interact with emotion processing in IFG are poorly understood. We used 4.7 T fMRI in 20 healthy young adults performing a rapid event-related emotional Go/NoGo task. This task combined the Go/NoGo task, which is a classic means of recruiting response inhibition processes, with emotionally neutral and aversive distractor images. In IFG, both response inhibition in an emotionally neutral context (neutral NoGo trials) and aversive emotional picture processing (aversive Go trials) evoked activation greater than the simple response baseline (neutral Go trials). These results are consistent with the literature. Activation for response inhibition in aversive contexts (aversive NoGo-neutral Go trials) was approximately the sum of response inhibition activation (neutral NoGo-neutral Go) and aversive emotional distractor activation (aversive Go-neutral Go). We conclude that response inhibition and aversive emotional stimulus processing activities combine additively (linearly) in IFG, rather than interfering with each other (sub linearly) or mutually-enhancing each other (super-linearly). We also found previously undocumented interaction effects between response inhibition (NoGo vs. Go) and emotional context (aversive vs. neutral distractor pictures) in bilateral posterior middle temporal gyrus and angular gyrus, right frontal eye field, and other brain regions. These results may reflect the interaction of attention processes driven by emotional stimuli with conflict resolution processes related to Go/NoGo performance. PMID- 22781162 TI - Significant correlation between a set of genetic polymorphisms and a functional brain network revealed by feature selection and sparse Partial Least Squares. AB - Brain imaging is increasingly recognised as an intermediate phenotype to understand the complex path between genetics and behavioural or clinical phenotypes. In this context, a first goal is to propose methods to identify the part of genetic variability that explains some neuroimaging variability. Classical univariate approaches often ignore the potential joint effects that may exist between genes or the potential covariations between brain regions. In this paper, we propose instead to investigate an exploratory multivariate method in order to identify a set of Single Nucleotide Polymorphisms (SNPs) covarying with a set of neuroimaging phenotypes derived from functional Magnetic Resonance Imaging (fMRI). Recently, Partial Least Squares (PLS) regression or Canonical Correlation Analysis (CCA) have been proposed to analyse DNA and transcriptomics. Here, we propose to transpose this idea to the DNA vs. imaging context. However, in very high-dimensional settings like in imaging genetics studies, such multivariate methods may encounter overfitting issues. Thus we investigate the use of different strategies of regularisation and dimension reduction techniques combined with PLS or CCA to face the very high dimensionality of imaging genetics studies. We propose a comparison study of the different strategies on a simulated dataset first and then on a real dataset composed of 94 subjects, around 600,000 SNPs and 34 functional MRI lateralisation indexes computed from reading and speech comprehension contrast maps. We estimate the generalisability of the multivariate association with a cross-validation scheme and demonstrate the significance of this link, using a permutation procedure. Univariate selection appears to be necessary to reduce the dimensionality. However, the significant association uncovered by this two-step approach combining univariate filtering and L1-regularised PLS suggests that discovering meaningful genetic associations calls for a multivariate approach. PMID- 22781163 TI - The effect of social observation on children's inhibitory control. AB - This study examined the effects of social observation on young children's performance during an inhibitory control task. In Experiment 1, children were randomly assigned to either a neutral, facilitation, or interference condition. In the neutral condition, children were presented with a standard black/white task. In the facilitation and interference conditions, children were asked to observe the task performance of another person, who gave either correct (facilitation) or incorrect (interference) responses, and then complete the task themselves. The results revealed that the performance of children in the interference condition was worse than in the other two conditions, but the difference between the two other conditions was not significant. The results of Experiment 2 show that social observation did not facilitate inhibitory control in children. These results suggest that social observation interferes with but does not facilitate inhibitory control in children. Therefore, social observation may interfere with certain aspects of executive function. PMID- 22781164 TI - Multiple sites of the cleavage of 17- and 19-mer encephalytogenic oligopeptides corresponding to human myelin basic protein (MBP) by specific anti-MBP antibodies from patients with systemic lupus erythematosus. AB - In contrast to canonical proteases, myelin basic protein (MBP)-Sepharose-purified IgG from multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients efficiently hydrolyze only MBP, but not many other tested proteins. It was shown that anti-MBP SLE IgGs cleave nonspecific tri- and tetrapeptides with an extremely low efficiency and cannot efficiently hydrolyse longer oligopeptides corresponding to antigenic determinants (AGDs) of HIV-1 integrase. To identify all sites of IgG-mediated proteolysis corresponding to two AGDs of MBP, we have used a combination of reverse-phase chromatography (RPhC), MALDI spectrometry, and TLC to analyze the cleavage products of two (17- and 19-mer) encephalytogenic oligopeptides corresponding to these AGDs. Both oligopeptides contained several clustered major and minor sites of cleavage. The active sites of anti-MBP abzymes are localized on their light chains, while the heavy chains are responsible for the affinity of protein substrates. Interactions of intact globular proteins with both light and heavy chains of abzymes provide high specificity of MBP hydrolysis. The affinity of anti-MBP abzymes for intact MBP was ~10(3)-fold higher than for the oligopeptides. The data suggest that both oligopeptides interact mainly with the light chain of different monoclonal abzymes of total pool of IgGs, which possesses lower affinity for substrates, and therefore, depending on the oligopeptide sequences, their hydrolysis may be less specific. PMID- 22781165 TI - Ghrelin effect on nutritional indices, midgut and fat body of Lymantria dispar L. (Lymantriidae). AB - Ghrelin is a 28-amino acid peptide that has significant effects on appetite and growth in humans and animals. The aim of this study was to examine 4th instar larvae of the pest insect Lymantria dispar L. after ghrelin treatment. Parameters included changes in nutritional indices (efficiency of conversion of ingested food, efficiency of conversion of digested food, approximate digestibility); midgut and fat body mass; total proteases, trypsin and leucine aminopeptidase activities in the midgut; number, height and width of columnar and goblet cells and their nuclei in the midgut epithelium and detection of ghrelin-like immunoreactivity in the midgut tissue. Four subpicomolar injections of ghrelin (0.3pmol) or physiological saline (control) were applied every 24h. The nutritional indices were higher in the ghrelin treated than in the control group. Ghrelin treatment was also associated with elevation of midgut mass, induced digestive enzyme activities, increased fat body mass and morphometric changes in columnar and goblet cells. This is the first report of the presence of ghrelin like hormone in endocrine cells of an insect midgut. Such information provides additional evidence for application of this relatively simple model system in the future studies of the mechanisms underlying of digestion and energy balance in more complex organisms. PMID- 22781166 TI - Patients' beliefs about the causes, persistence and control of psychotic experiences predict take-up of effective cognitive behaviour therapy for psychosis. AB - BACKGROUND: There is evidence that patients with schizophrenia benefit from standard cognitive behaviour therapy (CBT) only if active techniques are used ('full therapy'). By contrast, attending sessions but not proceeding beyond engagement and assessment strategies ('partial therapy'), or simply not attending sessions ('no therapy'), is not associated with better outcomes. The factors leading to full therapy are unknown. We hypothesized that patients' initial ideas about the nature and extent of their problems would predict use of CBT. A match between patients' views of their problems and the principles underlying treatment would lead to better outcomes. METHOD: Ninety-two patients with a recent relapse of psychosis completed the Illness Perception Questionnaire (IPQ) before receiving CBT. We examined whether their illness perceptions predicted the take up of therapy. RESULTS: Patients who did not attend sessions believed their problems would not last as long as those who attended them. Those who attended sessions but did not proceed to full therapy had a lower sense of control over their problems and a more biological view of their causes. Patients who took up full therapy were more likely to attribute the cause of their problems to their personality and state of mind. The take-up of therapy was predicted neither by levels of psychiatric symptoms nor by insight. CONCLUSIONS: People with psychosis who have psychologically orientated views of their problems, including the potential to gain control over them, may be more likely to engage fully and do well with standard CBT for psychosis, irrespective of the severity of their problems. PMID- 22781167 TI - Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. AB - Despite increasing evidence of oxidative stress in the pathophysiology of autism, most studies have not evaluated biomarkers within specific brain regions, and the functional consequences of oxidative stress remain relatively understudied. We examined frozen samples from the cerebellum and temporal cortex (Brodmann area 22 (BA22)) from individuals with autism and unaffected controls (n=15 and n=12 per group, respectively). Biomarkers of oxidative stress, including reduced glutathione (GSH), oxidized glutathione (GSSG) and glutathione redox/antioxidant capacity (GSH/GSSG), were measured. Biomarkers of oxidative protein damage (3 nitrotyrosine; 3-NT) and oxidative DNA damage (8-oxo-deoxyguanosine; 8-oxo-dG) were also assessed. Functional indicators of oxidative stress included relative levels of 3-chlorotyrosine (3-CT), an established biomarker of a chronic inflammatory response, and aconitase activity, a biomarker of mitochondrial superoxide production. Consistent with previous studies on plasma and immune cells, GSH and GSH/GSSG were significantly decreased in both autism cerebellum (P<0.01) and BA22 (P<0.01). There was a significant increase in 3-NT in the autism cerebellum and BA22 (P<0.01). Similarly, 8-oxo-dG was significantly increased in autism cerebellum and BA22 (P<0.01 and P=0.01, respectively), and was inversely correlated with GSH/GSSG in the cerebellum (P<0.01). There was a significant increase in 3-CT levels in both brain regions (P<0.01), whereas aconitase activity was significantly decreased in autism cerebellum (P<0.01), and was negatively correlated with GSH/GSSG (P=0.01). Together, these results indicate that decreased GSH/GSSG redox/antioxidant capacity and increased oxidative stress in the autism brain may have functional consequence in terms of a chronic inflammatory response, increased mitochondrial superoxide production, and oxidative protein and DNA damage. PMID- 22781168 TI - Detection of an immature dentate gyrus feature in human schizophrenia/bipolar patients. AB - Hippocampus-associated cognitive impairments are a common, highly conserved symptom of both schizophrenia (SCZ) and bipolar disorder (BPD). Although the hippocampus is likely an impacted region in SCZ/BPD patients, the molecular and cellular underpinnings of these impairments are difficult to identify. An emerging class of mouse models for these psychiatric diseases display similar cognitive impairments to those observed in human patients. The hippocampi of these mice possess a conserved pathophysiological alteration; we term the 'immature dentate gyrus' (iDG), characterized by increased numbers of calretinin positive immature neuronal progenitors, a dearth of calbindin-positive mature neurons and (often) constitutively increased neurogenesis. Although these models provide a link between cellular dysfunction and behavioral alteration, limited translational validity exists linking the iDG to human pathophysiology. In this study, we report the initial identification of an iDG-like phenotype in the hippocampi of human SCZ/BPD patients. These findings suggest a new motif for the etiology of these diseases and link an emerging class of mouse models to the human disease condition. PMID- 22781169 TI - Evidence for the involvement of ZNF804A in cognitive processes of relevance to reading and spelling. AB - Previous studies have shown that individuals with schizophrenia and dyslexia display common neurocognitive abnormalities. The aim of the present study was to determine whether known schizophrenia-risk genes contribute to dyslexia risk or to disease-relevant cognitive functions. For this purpose, we genotyped the schizophrenia-associated risk variants within zinc-finger protein 804A (ZNF804A), transcription-factor 4 and neurogranin in a large dyslexia case-control sample. We tested all variants for association with dyslexia (927 cases, 1096 controls), and with eight language-relevant cognitive processes (1552 individuals). We observed six significant associations between language-relevant traits and the ZNF804A-variant rs1344706. Interestingly, the ZNF804A schizophrenia risk variant was associated with a better cognitive performance in our data set. This finding might be consistent with a previously reported ZNF804A association in schizophrenia, in which patients carrying the schizophrenia-risk allele at rs1344706 showed a better performance in two memory tests. In conclusion, the present study provides evidence that ZNF804A might have a role in cognitive traits of relevance to reading and spelling, and underlines the phenotypic complexity that might be associated with ZNF804A. PMID- 22781171 TI - The effect of adverse rearing environments on persistent memories in young rats: removing the brakes on infant fear memories. AB - Mental health problems are often assumed to have their roots in early-life experiences. However, memories acquired in infancy are rapidly forgotten in nearly all species (including humans). As yet, a testable mechanism on how early life experiences have a lasting impact on mental health is lacking. In these experiments, we tested the idea that infant adversity leads to an early transition into adult-like fear retention, allowing infant memories to have a longer-lasting influence. Rats were exposed to maternal separation (3 h per day) across postnatal days (P) 2-14, or their mother was given corticosterone in her drinking water across the same period. Infant rats were then trained to fear a conditioned stimulus (CS) paired with an aversive unconditioned stimulus (US) on P17. Retention of the fear association was then tested 1-55 days later. When tested one day after the CS-US association was formed, both standard-reared (SR) and maternally-separated (MS) rats exhibited strong memory. However, when tested 10 days later, SR rats exhibited robust forgetting, whereas MS rats exhibited near-perfect retention. These effects were mimicked by exposing the mother to the stress hormone corticosterone in the drinking water. Finally, fear associations in P17 MS rats were retained for up to 30 days. Our findings point to differences in retention of fear as one factor that might underlie the propensity of stress exposed individuals to exhibit early anxiety symptoms and suggest that manipulations of the corticosterone system may hold the key to ameliorating some of the effects of early stress on persistent retention of fear. PMID- 22781170 TI - The tyrosine phosphatase STEP: implications in schizophrenia and the molecular mechanism underlying antipsychotic medications. AB - Glutamatergic signaling through N-methyl-D-aspartate receptors (NMDARs) is required for synaptic plasticity. Disruptions in glutamatergic signaling are proposed to contribute to the behavioral and cognitive deficits observed in schizophrenia (SZ). One possible source of compromised glutamatergic function in SZ is decreased surface expression of GluN2B-containing NMDARs. STEP(61) is a brain-enriched protein tyrosine phosphatase that dephosphorylates a regulatory tyrosine on GluN2B, thereby promoting its internalization. Here, we report that STEP(61) levels are significantly higher in the postmortem anterior cingulate cortex and dorsolateral prefrontal cortex of SZ patients, as well as in mice treated with the psychotomimetics MK-801 and phencyclidine (PCP). Accumulation of STEP(61) after MK-801 treatment is due to a disruption in the ubiquitin proteasome system that normally degrades STEP(61). STEP knockout mice are less sensitive to both the locomotor and cognitive effects of acute and chronic administration of PCP, supporting the functional relevance of increased STEP(61) levels in SZ. In addition, chronic treatment of mice with both typical and atypical antipsychotic medications results in a protein kinase A-mediated phosphorylation and inactivation of STEP(61) and, consequently, increased surface expression of GluN1/GluN2B receptors. Taken together, our findings suggest that STEP(61) accumulation may contribute to the pathophysiology of SZ. Moreover, we show a mechanistic link between neuroleptic treatment, STEP(61) inactivation and increased surface expression of NMDARs, consistent with the glutamate hypothesis of SZ. PMID- 22781172 TI - A molecular characterization of the choroid plexus and stress-induced gene regulation. AB - The role of the choroid plexus (CP) in brain homeostasis is being increasingly recognized and recent studies suggest that the CP has a more important role in physiological and pathological brain functions than currently appreciated. To obtain additional insight on the CP function, we performed a proteomics and transcriptomics characterization employing a combination of high resolution tandem mass spectrometry and gene expression analyses in normal rodent brain. Using multiple protein fractionation approaches, we identified 1400 CP proteins in adult CP. Microarray-based comparison of CP gene expression with the kidney, cortex and hippocampus showed significant overlap between the CP and the kidney. CP gene profiles were validated by in situ hybridization analysis of several target genes including klotho, CLIC 6, OATP 14 and Ezrin. Immunohistochemical analyses were performed for CP and enpendyma detection of several target proteins including cytokeratin, Rab7, klotho, tissue inhibitor of metalloprotease 1 (TIMP1), MMP9 and glial fibrillary acidic protein (GFAP). The molecular functions associated with various proteins of the CP proteome indicate that it is a blood cerebrospinal fluid (CSF) barrier that exhibits high levels of metabolic activity. We also analyzed the gene expression changes induced by stress, an exacerbating factor for many illnesses, particularly mood disorders. Chronic stress altered the expression of several genes, downregulating 5HT2C, glucocorticoid receptor and the cilia genes IFT88 and smoothened while upregulating 5HT2A, BDNF, TNFalpha and IL-1b. The data presented here attach additional significance to the emerging importance of CP function in brain health and CNS disease states. PMID- 22781173 TI - Association between older age and adverse outcomes on antiretroviral therapy: a cohort analysis of programme data from nine countries. AB - CONTEXT: Recent studies have highlighted the increased risk of adverse outcomes among older patients on antiretroviral therapy (ART). We report on the associations between older age and adverse outcomes in HIV/AIDS antiretroviral programmes across 17 programmes in sub-Saharan Africa. METHODS: We included data from nine countries: Central African Republic, Cote d'Ivoire, Democratic Republic of Congo, Ethiopia, Nigeria, Republic of Congo, Uganda, Zambia and Zimbabwe. We describe survival probability for progression to death and loss to follow-up for patients initiating ART aged less than 50 years and at least 50 years. Multivariate Cox proportional hazards models were used to assess the association between age (15-39, 40-49, 50-59, 60-69 and 70-94 years) and adverse outcomes adjusting for confounders identified a priori. RESULTS: Our analysis included 17,561 patients followed for a median of 12 months. The majority (65%) were female and 6672 (38%) were severely immunosuppressed at baseline. Median age at ART initiation was 36.0 years (interquartile range 30.1-42.8); 11.4% of patients were aged at least 50 years. Median gain in CD4 cell count at 6 and 12 months was significantly higher in patients less than 50 years old compared with those at least 50 years (134 vs. 112 cells/MUl at 6 months; 170 vs. 139 cells/MUl at 12 months; both P < 0.001). In multivariate analysis, there was a significant increased risk of mortality beyond 3 months after ART initiation in all age groups of at least 40 years of age compared with less than 40 years [40-49 years adjusted hazard ratios (aHRs) 1.59, P < 0.001; 50-59 years aHR 1.58, P = 0.002; 60-69 years aHR 2.63, P < 0.001; 70-94 years aHR 3.64, P = 0.004). CONCLUSION: Older age groups represent an important proportion of the overall treatment cohort in these sub-Saharan Africa programmes, and risk of mortality increased as age increased. Future research should be directed at further understanding the reasons for higher mortality, and defining simple interventions that are feasible in highly under-resourced settings to allow for adapted follow-up and care approaches for older age groups. PMID- 22781175 TI - The impact of antiretroviral treatment on the age composition of the HIV epidemic in sub-Saharan Africa. AB - INTRODUCTION: Antiretroviral treatment (ART) coverage is rapidly expanding in sub Saharan Africa (SSA). Based on the effect of ART on survival of HIV-infected people and HIV transmission, the age composition of the HIV epidemic in the region is expected to change in the coming decades. We quantify the change in the age composition of HIV-infected people in all countries in SSA. METHODS: We used STDSIM, a stochastic microsimulation model, and developed an approach to represent HIV prevalence and treatment coverage in 43 countries in SSA, using publicly available data. We predict future trends in HIV prevalence and total number of HIV-infected people aged 15-49 years and 50 years or older for different ART coverage levels. RESULTS: We show that, if treatment coverage continues to increase at present rates, the total number of HIV-infected people aged 50 years or older will nearly triple over the coming years: from 3.1 million in 2011 to 9.1 million in 2040, dramatically changing the age composition of the HIV epidemic in SSA. In 2011, about one in seven HIV-infected people was aged 50 years or older; in 2040, this ratio will be larger than one in four. CONCLUSION: The HIV epidemic in SSA is rapidly ageing, implying changing needs and demands in many social sectors, including health, social care, and old-age pension systems. Health policymakers need to anticipate the impact of the changing HIV age composition in their planning for future capacity in these systems. PMID- 22781176 TI - Antiretroviral therapy adherence and drug-drug interactions in the aging HIV population. AB - It is estimated that by 2015 more than half of all HIV-infected individuals in the United States will be 50 years of age or older. As this population ages, the frequency of non-AIDS related comorbidities increases, which includes cardiovascular, metabolic, gastrointestinal, genitourinary and psychiatric disorders. As a result, medical management of the aging HIV population can be complicated by polypharmacy and higher pill burden, leading to poorer antiretroviral therapy (ART) adherence. Adherence to ART is generally better in older populations when compared to younger populations; however, cognitive impairment in elderly patients can impair adherence, leading to worse treatment outcomes. Practical monitoring tools can improve adherence and increase rates of viral load suppression. Several antiretroviral drugs exhibit inhibitory and/or inducing effects on cytochrome P450 isoenzymes, which are responsible for the metabolism of many medications used for the treatment of comorbidities in the aging HIV population. The combination of ART with polypharmacy significantly increases the chance of potentially serious drug-drug interactions (DDIs), which can lead to drug toxicity, poorer ART adherence, loss of efficacy of the coadministered medication, or virologic breakthrough. Increasing clinicians awareness of common DDIs and the use of DDI programs can prevent coadministration of potentially harmful combinations in elderly HIV-infected individuals. Well designed ART adherence interventions and DDI studies are needed in the elderly HIV population. PMID- 22781174 TI - Lessons learned from the first wave of aging with HIV. AB - In this perspective piece, the authors consider what has been learned and is being studied about aging with HIV in resource-rich settings. The authors argue that although there is much that will be different about aging with HIV in other parts of the globe, there are common themes and approaches to care. These include the observation that most patients have more than one health condition, and the need to assess individual risk, prioritize care, and consider the total burden of disease when considering further testing and treatment. PMID- 22781177 TI - Prevalence of HIV and chronic comorbidities among older adults. AB - OBJECTIVES: Limited evidence is available on HIV, aging and comorbidities in sub Saharan Africa. This article describes the prevalence of HIV and chronic comorbidities among those aged 50 years and older in South Africa using nationally representative data. DESIGN: The WHO's Study of global AGEing and adult health (SAGE) was conducted in South Africa in 2007-2008. SAGE includes nationally representative cohorts of persons aged 50 years and older, with comparison samples of those aged 18-49 years, which aims to study health and its determinants. METHODS: Logistic and linear regression models were applied to data from respondents aged 50 years and older to determine associations between age, sex and HIV status and various outcome variables including prevalence of seven chronic conditions. RESULTS: HIV prevalence among adults aged 50 and older in South Africa was 6.4% and was particularly elevated among Africans, women aged 50 59 and those living in rural areas. Rates of chronic disease were higher among all older adults compared with those aged 18-49. Of those aged 50 years and older, 29.6% had two or more of the seven chronic conditions compared with 8.8% of those aged 18-49 years (P < 0.0001). When controlling for age and sex among those aged 50 and older, BMI was lower among HIV-infected older adults aged 50 and older (27.5 kg/m2) than in HIV-uninfected individuals of the same age (30.6) (P < 0.0001). Grip strength among HIV-infected older adults was significantly (P=0.004) weaker than among similarly-aged HIV-uninfected individuals. CONCLUSION: HIV-infected older adults in South Africa have high rates of chronic disease and weakness. Studies are required to examine HIV diagnostics and treatment instigation rates among older adults to ensure equity of access to quality care, as the number and percentage of older adults living with HIV is likely to increase. PMID- 22781178 TI - Cancer and the 'other' noncommunicable chronic diseases in older people living with HIV/AIDS in resource-limited settings: a challenge to success. AB - OBJECTIVE: There is considerable research around the morbidity and mortality related to noncommunicable diseases (NCDs), particularly cardiovascular disease and diabetes, among people living with HIV/AIDS (PLWHA) in resource-richer settings. Less is known about the burden and appropriate management of NCDs, particularly 'other' NCDs including cancer, renal, pulmonary, neurocognitive and mental health conditions, among older PLWHA in resource-limited settings (RLSs). We undertook a literature review of these other NCDs to explore what is currently known about them and identify areas of further research. METHODS: Systematic literature review of published manuscripts and selected conference abstracts and reports. RESULTS: Although there is growing recognition of the importance of these NCDs among the aging population of PLWHA in RLSs, significant gaps remain in understanding the epidemiology and risk factors among older PLWHA in these settings. Even more concerning is the limited available evidence for effective and feasible approaches to prevention, screening and treatment of these conditions. The burden of these NCDs is related to both the aging of the population of PLWHA and an increased risk due to HIV infection, other comorbidities associated with HIV infection or transmission risk and underlying risk factors in the general community. Results from resource-richer settings and RLSs highlight malignancies, neurocognitive and mental health as well as renal disease as the most significant challenges currently and likely to increase in the future. CONCLUSION: Although some lessons can be taken from the growing experience with NCDs in older PLWHA in resource-richer settings, additional research is needed to better understand their risk and impact and identify optimal models of care to effectively address this challenge in the areas where the majority of older PLWHA will be receiving care. PMID- 22781179 TI - Toward a systemic research agenda for addressing the joint epidemics of HIV/AIDS and noncommunicable diseases. AB - A growing proportion of people living with HIV/AIDS also struggle to cope with one or several noncommunicable diseases (NCDs), particularly as they age. The two epidemics being intertwined, there is increasing recognition that that there should be closer advocacy, policy and programmatic links between HIV and NCDs. The objective of this paper is to discuss the development of a research agenda geared towards informing the design and implementation of programs and policies truly grounded in a co-benefits approach. Tackling the joint epidemics of HIV/AIDS and NCDs in Africa will require for research funders and private and foreign aid donors to be bold, visionary and to commit to long-term research investments in order to evaluate the effects of natural policy experiments and complex interventions. PMID- 22781180 TI - HIV, aging and continuity care: strengthening health systems to support services for noncommunicable diseases in low-income countries. AB - Although health systems in most low-income countries largely provide episodic care for acute symptomatic conditions, many HIV programs have developed effective, locally owned and contextually appropriate policies, systems and tools to support chronic care services for persons living with HIV (PLWH). The continuity of care provided by such programs may be especially critical for older PLWH, who are at risk for more rapid progression of disease and are more likely to have complications of HIV and its treatment than their younger counterparts. Older PLWH are also more likely to have other chronic noncommunicable diseases (NCDs), including hypertension, diabetes, cancers and chronic lung disease. As the number of older PLWH rises, enhanced chronic care systems will be required to optimize their health and wellbeing. These systems, lessons and resources can also be leveraged to support the burgeoning numbers of HIV-negative individuals with chronic NCD in need of ongoing care. PMID- 22781181 TI - HIV and Africa's elderly: the problems and possibilities. AB - Demographic changes and the increasing availability and coverage of antiretroviral therapy imply that the burden of HIV is shifting to older age groups in sub-Saharan Africa. However, very little is known about the burden of disease and the unique considerations required to adequately treat and retain older Africans. In this review, we summarize the epidemiological data on HIV prevalence among older Africans, and review progress and barriers to accessing treatment and care. The unique clinical considerations distinguishing the management of older HIV-infected Africans are summarized, with a focus on cardiovascular disease, neuropsychiatric conditions, oncologic illness, and musculoskeletal morbidity. The review concludes by suggesting opportunities for improving our knowledge about and management of HIV among older Africans, including prevention opportunities and potential technologies, including a polypill for reducing comorbidity in this under-recognized highly vulnerable group. PMID- 22781183 TI - Capillary electrophoresis-based immunoassay for the determination of brevetoxin-B in shellfish using electrochemical detection. AB - Neurotoxic shellfish poisoning is a significant food-borne disease caused by potent cyclic polyether toxins (brevetoxins) that accumulate in the flesh of shellfish. Here we report a new procedure for brevetoxin analysis by capillary electrophoresis-based immunoassay (CE-IA) with electrochemical (EC) detection. In this method, after the competitive immunoreaction in liquid phase, the horseradish peroxidase (HRP)-labeled antigen and the bound enzyme-labeled complex were separated and then the system of HRP catalyzing H(2)O(2)-o-aminophenol reaction was adopted. The limits of detection (signal-to-noise = 3) was determined to be 0.1 ng/mL. Intra-day relative standard deviations (RSD, n = 5) for migration time and peak area were 3.6 and 4.5%, respectively. Inter-day RSD was 6.9 and 7.8% for migration time and peak area, respectively. The CE-IA with EC detection provides a sensitive analytical approach, not previously available, for the determination of brevetoxin-B in shellfish samples. PMID- 22781184 TI - The determination of GC-MS relative molar responses of some n-alkanes and their halogenated analogs. AB - The dependence of relative response factors on the carbon atom number related to naphthalene has been investigated in homologous series by using gas chromatography-mass spectrometry. Relative responses of some straight chain aliphatic n-alkanes and their halogenated derivatives (chlorine, bromine and iodine) were compared in the experiments. Linear correlations were found between the molecular structures; i.e., the carbon atom number and relative molar response in current homologous series. In conclusion, mass spectrometric detection combined with gas chromatography was less sensitive to n-alkanes than to their derivatives containing a chlorine, bromine or iodine atom. After n alkanes, mass spectrometric responses increase in the order of 1-chloroalkanes, 1 bromoalkanes and 1-iodoalkanes. These results are in accordance with electron ionization cross section data for n-alkyl-derivatives. The relative molar responses of the individual CH(2) groups are between 0.171 and 0.178 in the homologous series. The increments of chlorine, bromine and iodine atoms to the relative molar responses are 0.081, 0.141 and 0.492, respectively. Based on these results, the addivity rule is valid for both halogen atoms and CH(2) groups in the case of mono-substituted n-haloalkanes. The results of this study show a significant departure from the additivity rule in the case of polyhalogenated alkanes and alkenes. However, the relative molar response can be calculated by means of simultaneously measuring other compounds. Further study is needed about how to influence the relative molar responses as a function of various experimental parameters. PMID- 22781185 TI - Septum bleed during GC-MS analysis: utility of septa of various makes. AB - The significant presence of septum-related ghost peaks, causing interference in routine gas chromatography-mass spectrometry analyses at sample injection port temperatures above 100 degrees C, is demonstrated. A comparative study with commonly employed septa of various types and makes under varying analytical conditions, e.g., injection port temperature, carrier flow rate, capillary column type and oven heating rate reveal that long-chain hydrocarbons, substituted phthalate derivatives and silanes (silicon compounds) are responsible for such interferences, which is confirmed from their respective peak fragmentation patterns after comparison with standard mass spectrometry library data. Consequently, prior blank studies at actual analysis conditions may become mandatory for quantification and reduction of such interferences, ignoring septa quality and performance claims. PMID- 22781186 TI - Effect of Zingiber officinale R. rhizomes (ginger) on pain relief in primary dysmenorrhea: a placebo randomized trial. AB - BACKGROUND: Zingiber officinale R. rhizome (ginger) is a popular spice that has traditionally been used to combat the effects of various inflammatory diseases. The aim of this study was to evaluate the effects of ginger on pain relief in primary dysmenorrhea. METHOD: This was a randomized, controlled trial. The study was based on a sample of one hundred and twenty students with moderate or severe primary dysmenorrhea. The students were all residents of the dormitories of Shahed University. They were randomly assigned into two equal groups, one for ginger and the other for placebo in two different treatment protocols with monthly intervals. The ginger and placebo groups in both protocols received 500 mg capsules of ginger root powder or placebo three times a day. In the first protocol ginger and placebo were given two days before the onset of the menstrual period and continued through the first three days of the menstrual period. In the second protocol ginger and placebo were given only for the first three days of the menstrual period. Severity of pain was determined by a verbal multidimensional scoring system and a visual analogue scale. RESULTS: There was no difference in the baseline characteristics of the two groups (placebo n = 46, ginger n = 56). The results of this study showed that there were significant differences in the severity of pain between ginger and placebo groups for protocol one (P = 0.015) and protocol two (P = 0.029). There was also significant difference in duration of pain between the two groups for protocol one (P = 0.017) but not for protocol two (P = 0.210). CONCLUSION: Treatment of primary dysmenorrhea in students with ginger for 5 days had a statistically significant effect on relieving intensity and duration of pain. TRIAL REGISTRATION: IRCT201105266206N3. PMID- 22781187 TI - Genetic advances of type 2 diabetes in Chinese populations. AB - In recent decades, the prevalence of type 2 diabetes in China has increased significantly, underscoring the importance of investigating the etiological mechanisms, including genetic determinants, of the disease in Chinese populations. Numerous loci conferring susceptibility to type 2 diabetes (T2D) have been identified worldwide, with most having been identified in European populations. In terms of ethnic heterogeneity in pathogenesis as well as disease predisposition, it is imperative to explore the specific genetic architecture of T2D in Han Chinese. Replication studies of European-derived susceptibility loci have been performed, validating 11 of 32 loci in Chinese populations. Genetic investigations into heritable traits related to glucose metabolism are expected to provide new insights into the pathogenesis of T2D, and such studies have already inferred some new susceptibility loci. Other than replication studies of European-derived loci, efforts have been made to identify specific susceptibility loci in Chinese populations using methods such as genome-wide association studies. These efforts have identified additional new loci for the disease. Genetic studies can facilitate the prediction of risk for T2D and also promote individualized anti-diabetic treatment. Despite many advances in the field of risk prediction and pharmacogenetics, the pace of clinical application of these findings is rather slow. As a result, more studies into the practical utility of these findings remain necessary. PMID- 22781188 TI - Improved photovoltaic performances by post-deposition acidic treatments on tetrapod shaped colloidal nanocrystal solids. AB - The ligand exchange reaction with pyridine is the standard procedure for the integration of colloidal semiconductor nanocrystals (NCs) in photovoltaic devices; however, for large sized and irregularly shaped branched NCs, such as CdSe@CdTe tetrapods, this procedure can lead to a considerable waste of materials and the aggregation of NCs in the colloidal solution, therefore resulting in the formation of an inhomogeneous film and low device performances. Here, we report on alternative post-deposition treatments with carboxylic acids on films of CdSe@CdTe tetrapod shaped NCs. This approach guarantees the removal of the insulating surfactant, necessary to obtain good charge transport among NCs, while preserving the film integrity. We perform a complete characterization of the nanocrystalline films treated with different carboxylic acids and demonstrate the successful integration of such films in photovoltaic devices, showing a doubled efficiency with respect to the standard ligand exchange procedure. Our approach represents a general route towards the development of NC based devices with improved performances and minimized waste of material. PMID- 22781189 TI - Effect of substitution at N"-position of N'-hydroxy-N-amino guanidines on tumor cell growth. AB - Structural modification of one of our earlier reported lead molecule (ABNM13) has been carried out to study the effect of different substituents at the N"-position of N-hydroxy-N'-amino guanidines (HAGs) on their anticancer activity. Compounds with electron donating substituents were found to be less active. In contrast, those with electron withdrawing groups were found favorable for anticancer activity. The obtained results provide significant SAR information that may be useful for further drug designing with HAGs. PMID- 22781190 TI - Synthesis and evaluation of aplysinopsin analogs as inhibitors of human monoamine oxidase A and B. AB - Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms. Previous studies have shown aplysinopsin analogs to possess a variety of biological activities, including modulation of neurotransmissions. A series of fifty aplysinopsin analogs was synthesized and assayed for monoamine oxidase A and B inhibitory activity. Three compounds displayed significant MAO inhibitory activity and selectivity. The compound (E)-5 [(6-bromo-1H-indol-3-yl)methylene]-2-imino-1,3-dimethylimidazolidin-4-one (3x) possessed an IC(50) of 5.6 nM at MAO-A and had a selectivity index of 80.24. An SAR study revealed that multiple N-methylations, one of which should be at position N-2', and bromination at C-5 or C-6 are important factors for MAO-A potency and selectivity. PMID- 22781191 TI - Healthcare information technology and economics. AB - At the 2011 American College of Medical Informatics (ACMI) Winter Symposium we studied the overlap between health IT and economics and what leading healthcare delivery organizations are achieving today using IT that might offer paths for the nation to follow for using health IT in healthcare reform. We recognized that health IT by itself can improve health value, but its main contribution to health value may be that it can make possible new care delivery models to achieve much larger value. Health IT is a critically important enabler to fundamental healthcare system changes that may be a way out of our current, severe problem of rising costs and national deficit. We review the current state of healthcare costs, federal health IT stimulus programs, and experiences of several leading organizations, and offer a model for how health IT fits into our health economic future. PMID- 22781192 TI - Using domain knowledge and domain-inspired discourse model for coreference resolution for clinical narratives. AB - OBJECTIVE: This paper presents a coreference resolution system for clinical narratives. Coreference resolution aims at clustering all mentions in a single document to coherent entities. MATERIALS AND METHODS: A knowledge-intensive approach for coreference resolution is employed. The domain knowledge used includes several domain-specific lists, a knowledge intensive mention parsing, and task informed discourse model. Mention parsing allows us to abstract over the surface form of the mention and represent each mention using a higher-level representation, which we call the mention's semantic representation (SR). SR reduces the mention to a standard form and hence provides better support for comparing and matching. Existing coreference resolution systems tend to ignore discourse aspects and rely heavily on lexical and structural cues in the text. The authors break from this tradition and present a discourse model for "person" type mentions in clinical narratives, which greatly simplifies the coreference resolution. RESULTS: This system was evaluated on four different datasets which were made available in the 2011 i2b2/VA coreference challenge. The unweighted average of F1 scores (over B-cubed, MUC and CEAF) varied from 84.2% to 88.1%. These experiments show that domain knowledge is effective for different mention types for all the datasets. DISCUSSION: Error analysis shows that most of the recall errors made by the system can be handled by further addition of domain knowledge. The precision errors, on the other hand, are more subtle and indicate the need to understand the relations in which mentions participate for building a robust coreference system. CONCLUSION: This paper presents an approach that makes an extensive use of domain knowledge to significantly improve coreference resolution. The authors state that their system and the knowledge sources developed will be made publicly available. PMID- 22781193 TI - Electrochemical intermediate species and reaction pathway in H2 oxidation on solid electrolytes. AB - We use spatially resolved photoelectron spectroscopy performed in operando to identify the reaction intermediates of the hydrogen electro-oxidation reaction on yttria-stabilized zirconia (YSZ) electrolytes with Pt electrodes. We find that hydroxyl on the zirconia electrolyte is a reaction intermediate in the hydrogen oxidation reaction and that it participates in the rate-determining step. In contrast to the general wisdom, the limiting step does not involve the transfer of charge. These results allow us to propose the detailed reaction pathway, which provides direct insight into how to accelerate the kinetics. PMID- 22781194 TI - Pre-infection physical exercise decreases mortality and stimulates neurogenesis in bacterial meningitis. AB - Physical exercise has been shown to increase neurogenesis, to decrease neuronal injury and to improve memory in animal models of stroke and head trauma. Therefore, we investigated the effect of voluntary wheel running on survival, neuronal damage and cell proliferation in a mouse model of pneumococcal meningitis. Mice were housed in cages equipped with voluntary running wheels or in standard cages before induction of bacterial meningitis by a subarachnoid injection of a Streptococcus pneumoniae type 3 strain. 24 hours later antibiotic treatment was initiated with ceftriaxone (100 mg/kg twice daily). Experiments were terminated either 30 hours or 4 days (short-term) or 7 weeks (long-term) after infection, and the survival time, inflammatory cytokines and corticosterone levels, neurogenesis in the dentate gyrus of the hippocampal formation and the cognitive function were evaluated in surviving mice. Survival time was significantly increased in running mice compared to control animals (p = 0.0087 in short-term and p = 0.016 in long-term experiments, log-rank test). At the end of the long-term experiment, mortality was lower in trained than in sedentary animals (p = 0.031, Fisher's Exact test). Hippocampal neurogenesis--assessed by the density of doublecortin-, TUC-4- and BrdU + NeuN-colabeled cells--was significantly increased in running mice in comparison to the sedentary group after meningitis. However, Morris water maze performance of both groups 6 weeks after bacterial meningitis did not reveal differences in learning ability. In conclusion, physical exercise prior to infection increased survival in a mouse model of bacterial meningitis and stimulated neurogenesis in the dentate gyrus of the hippocampal formation. PMID- 22781196 TI - [Chronic obstructive pulmonary disease and inflammation: complexity and novel intervention]. PMID- 22781195 TI - [Early detection, early diagnosis and early intervention: the main research direction for the prevention and treatment of chronic obstructive pulmonary disease in China]. PMID- 22781197 TI - [Pulmonary embolism in patients with chronic obstructive pulmonary disease exacerbations of unknown origin: clinical characteristics and risk factors]. AB - OBJECTIVE: To evaluate the prevalence of pulmonary embolism(PE) in patients with chronic obstructive pulmonary disease (COPD) exacerbations of unknown origin and to explore the risk factors associated with PE. METHODS: A total of 208 consecutive patients with COPD were referred to this hospital for severe exacerbations of unknown origin. Their age was 50 - 82 years, with a mean of (62 +/- 12) years. All patients were examined within 48 h of admission by CT pulmonary angiography (CTPA) and lower extremity ultrasonography. The patients were classified as PE positive (positive results on CTPA) or PE negative (negative results on CTPA). Arterial blood gas, the levels of D-dimer and ET-1 were measured in all the patients. Differences between groups were analyzed using a two-tailed unpaired t test for normally distributed variables and a Mann Whitney u test for non-normally distributed variables. Qualitative data were assessed using chi-square test, and risk factors were analyzed using logistic regression analysis. RESULTS: The frequency of PE was 33% in this series of 208 consecutive patients with COPD referred for exacerbations of unknown origin. There were differences between PE positive and PE negative groups in the following factors (chi(2) = 4.32 - 6.79, mean P < 0.05): immobilization >= 7 days 21.7% (15/208) vs 13.7% (19/208); difference in circumference of lower limbs >= 1 cm 34.8% (24/208) vs 15.1% (21/208); deep venous thrombosis (DVT) 37.7% (26/208) vs 12.2% (17/208); syncope 11.6% (8/208) vs 0.06% (9/208); S(I)Q(III)T(III) syndrome 11.6% (8/208) vs 0.04% (5/208); decrease in PaCO2 >= 5 mm Hg (1 mm Hg = 0.133 kPa) 27.5% (19/208) vs 9.3% (13/208). Plasma D-dimer and ET-1 levels were significantly higher in patients with PE as compared to patients without PE. D dimer levels were (760 +/- 152) ug/L and (253 +/- 56) ug/L (Z = -2.946, P < 0.01); ET-1 levels were 5.4 ng/L (1.6 - 6.9 ng/L) and 1.8 ng/L (1.3 - 4.8 ng/L), Z = -2.532, P < 0.01. Risk factors identified by logistic regression analysis included immobilization >= 7 days (P < 0.05, OR = 3.24, 95%CI = 1.56 - 4.98), difference in circumference of lower limbs >= 1 cm (P < 0.05, OR = 2.56, 95%CI = 1.48 - 3.93), and deep venous thrombosis (DVT) (P < 0.05, OR = 2.31, 95%CI = 1.23 - 3.58). CONCLUSIONS: This study showed a 33% prevalence of PE in patients with COPD who were hospitalized for severe exacerbations of unknown origin. Immobilization >= 7 days, difference in circumference of lower limbs >= 1 cm, and DVT were risk factors for PE in this group of patients. PMID- 22781198 TI - [Evaluation of pulmonary arterial hypertension in chronic obstructive pulmonary disease by multislice spiral CT]. AB - OBJECTIVE: To investigate the use of multislice spiral CT (MSCT) in the diagnosis of pulmonary arterial hypertension (PAH) in patients with chronic obstructive pulmonary disease (COPD). METHODS: The diameters and areas of the pulmonary artery were measured in 81 cases with COPD and 100 normal adults from January to November 2011. The ratios of the diameters of the main pulmonary artery (MPA) to ascending aorta (AA), descending aorta (DA), trachea, thoracic vertebra (ThV) were also calculated. Data analysis used the t test of the 2 samples compared, multi-rate compared by chi(2) test. RESULTS: There were significant differences in the measured parameters between the COPD group and the control group. The differences were also significant among groups of COPD patients aged < 40 y, 40 - 60 y, > 60 y, and the control group, among patients with different stages of COPD (stage I, II, III, IV) and the control group, and among patients with sPAP > 50 mm Hg (1 mm Hg = 0.133 kPa), sPAP <= 50 mm Hg and the control group. There were positive correlations between sPAP and the measured indexes such as MPA [(3.14 +/ 0.63) cm] of pulmonary artery in COPD. There were negative correlations between FEV(1)% and some of the measured indexes such as MPA/T(d) (1.81 +/- 0.48). Multi indicators was no significant difference (chi(2) = 17.76, P > 0.05). CONCLUSIONS: MSCT is very useful in diagnosis of PAH in COPD. The diameter ratio of MPA to trachea, the area of MPA, and the diameter ratio of MPA to ThV can be used as diagnostic criteria for evaluation of PAH in COPD. PMID- 22781199 TI - [The efficacy of nebulized budesonide in acute moderate to severe exacerbations of asthma in children]. AB - OBJECTIVE: To evaluate the effect of nebulized budesonide (BUD) in acute moderate to severe exacerbations of asthma in children. METHODS: Forty children, 5 to 15 years of age, with acute moderate to severe attacks of asthma, were randomized into BUD group and control group, receiving nebulized 0.5% salbutamol (150 ug/kg) + 0.025% ipratropium bromide (1 ml) + 0.05% budesonide (2 ml) or nebulized 0.5% salbutamol (150 ug/kg) + 0.025% ipratropium bromide (1 ml) + saline (2 ml) at half-hourly intervals for 3 doses respectively. Lung function, respiratory rate (RR), heart rate(HR), oxygen saturation (SaO2) and clinical score (CS) were monitored. RESULTS: The baseline characteristics of the 2 groups were similar. After 3 doses of nebulization, CS, RR, SaO2, FEV(1) and FEV(1)% were significantly improved in both groups (P < 0.05). The CS in BUD group was significantly lower than that in control group at the end of 2 h after the third dose of nebulization 0 (0) vs 0 (1), Z = 2.522, P = 0.012. There were no significant differences in RR, HR and SaO2 between 2 groups (P > 0.05). The improvement of FEV(1)% in the first hour and the second hour after 3 doses of nebulization was 8.0 (6.8)% and 5.5 (6.5)% in BUD group, and 6.0 (8.5)% and 1.0 (6.5)% in control group, the improvement in BUD group being significantly greater than that in control group (Z = 2.270 and 2.686, P = 0.023 and 0.007 respectively). The improvement of FEV(1) in the second hour after 3 doses of nebulization was significantly greater in BUD group than in control group 0.07 (0.12) L vs 0.01 (0.10) L, Z = 2.455, P = 0.014. The full recovery rate in BUD group at the end of 2 h after completion of nebulization was significantly higher than that in control group (17/20, 85.0% vs 9/18, 50.0%, chi(2) = 5.371, P = 0.024). The proportion of patients who needed to use oral corticosteroids was significantly lower in BUD group than in control group (3/20, 15.0% vs 8/18, 44.4%, chi(2) = 3.993, P = 0.046). The hospitalization rate was 5% (1/20) in BUD group, and 17% (3/18) in control group, but the difference was not statistically significant (P > 0.05). CONCLUSION: Nebulized BUD in high dose and at short intervals combined with rapid-acting bronchodilators has an additional bronchodilator response, associated with more rapid and better improvement in clinical symptoms and lung function, indicating that it is preferred in the early management of acute moderate to severe exacerbation of asthma in children. PMID- 22781200 TI - [Procalcitonin-guided algorithms of antibiotic therapy in community-acquired lower respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials]. AB - OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of procalcitonin-guided algorithms of antibiotic therapy in lower respiratory tract infections. METHODS: Using procalcitonin, lower respiratory tract infections, community acquired pneumonia, exacerbations of COPD, exacerbations of chronic obstructive pulmonary diseases, acute bronchitis and asthma as key words, we searched relevant randomized controlled trials (RCT) from Pubmed, EMBASE, Cochrane Library, Chinese Journal Full-text Database, Chinese Biomedical Literature Database, and traced the related references to obtain the information that had not been found. The date of the search was from January of 1990 to December of 2010.We made quality assessment of qualified RCTs assessed by the exclusion and inclusion criteria and used RevMan 4.2.2 provided by the Cochrane Collaboration to perform meta-analysis. RESULTS: Five RCT involving 2322 patients were identified. There were significant differences between procalcitonin-guided treatment and standard treatment in duration of antibiotic treatment in days (WMD = -2.58 d, 95%CI: -3.13 to -2.04, Z = 9.36, P < 0.001), antibiotic prescription rate (OR = 0.23, 95%CI: 0.12 - 0.44, Z = 4.52, P < 0.001), antibiotic costs (WMD = USD-91.72, 95%CI: -109.44 to -74.00, Z = 10.15, P < 0.001) and persistent/relapsed infection rate (OR = 0.70, 95%CI: 0.5 - 0.97, Z = 2.13, P = 0.03). There were no statistical differences in rate of need for intensive care (OR = 0.8, 95%CI: 0.59 - 1.09, Z = 1.41, P = 0.16), in hospital mortality (OR = 1.01, 95%CI: 0.69 - 1.48, Z = 0.07, P = 0.94), length of hospital stay (WMD = 0.27 d, 95%CI: -0.9 - 0.35, Z = 0.86, P = 0.39), and clinical success rate (OR = 1.04, 95%CI: 0.65 - 1.65, Z = 0.16, P = 0.88). CONCLUSION: The implementation of a procalcitonin-based algorithm may reduce antibiotic exposure in patients with lower respiratory tract infections, but further research is necessary before the wide adoption of this strategy. PMID- 22781201 TI - [Effects of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation in rats]. AB - OBJECTIVE: To explore the influence of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation. METHODS: Male Sprague-Dawley rats were randomly divided into a control group and a chronic intermittent hypoxia group. Transcranial magnetic stimulation was applied in genioglossus motor cortex of the 2 groups. The responses of transcranial magnetic stimulation were recorded and analyzed by single factor analysis of variance. RESULTS: The anterolateral area provided an optimal motor evoked potential response to transcranial magnetic stimulation in the genioglossus motor cortex of the rats. Genioglossus motor evoked potential latency and amplitude were significantly modified by intermittent hypoxic exposure, with a significant decrease in latency (F = 3.294, P < 0.01) at the 1st day [(4.90 +/- 0.54) ms] and the 14th day [(4.64 +/- 1.71) ms], and an increase in amplitude (F = 1.905, P < 0.05) at the 1st day [(2.28 +/- 0.57) mV] and the 7th day [(1.89 +/- 0.20) mV]. CONCLUSION: Intermittent hypoxia could increase the transcranial magnetic stimulation response of genioglossus motor cortex in rats. PMID- 22781202 TI - [Chronic obstructive pulmonary disease and lung cancer: advances in the study of epigenetic modification enzymes]. PMID- 22781203 TI - [Progress in the mechanisms of chronic obstructive pulmonary disease co-morbid lung cancer]. PMID- 22781204 TI - Editors' Pick: A real Caucasian and the genetic investigation of Caucasus peoples. PMID- 22781205 TI - The hydrophobic mismatch determines the miscibility of ceramides in lipid monolayers. AB - The organization of lipids within membranes strongly depends on the interaction with other lipid and protein molecules. Sphingolipids comprise a structurally diverse family, the ceramides being some of the simplest members. Although small chemical modifications of ceramide structure, such as varying the N-acyl chain length, lead to a complex polymorphism of this lipid, only long acyl chain ceramides have usually been studied and their properties became a putative hallmark for all ceramides. In this work, we studied the mixing behavior of C10:0 Cer, which has the N-acyl chain shorter than that of the sphingosine acyl chain and displays an expanded to condensed phase transition at 25 mN m(-1) at 24 degrees C, with ceramides N-acylated with longer fatty acyl chains C12:0, C14:0 and C18:0. The N-acyl chain length determined the miscibility of ceramides in Langmuir monolayers, as it was ascertained by the dependence of the mean molecular area, perpendicular dipole moment, surface topography and film thickness with the mixture composition. We found that, as the hydrophobic mismatch in ceramides increased complete miscibility, partial or complete immiscibility can occur. PMID- 22781206 TI - Comparative study of depth-dependent characteristics of equine and human osteochondral tissue from the medial and lateral femoral condyles. AB - Articular cartilage defects are common after joint injuries. When left untreated, the biomechanical protective function of cartilage is gradually lost, making the joint more susceptible to further damage, causing progressive loss of joint function and eventually osteoarthritis (OA). In the process of translating promising tissue-engineering cartilage repair approaches from bench to bedside, pre-clinical animal models including mice, rabbits, goats, and horses, are widely used. The equine species is becoming an increasingly popular model for the in vivo evaluation of regenerative orthopaedic approaches. As there is also an increasing body of evidence suggesting that successful lasting tissue reconstruction requires an implant that mimics natural tissue organization, it is imperative that depth-dependent characteristics of equine osteochondral tissue are known, to assess to what extent they resemble those in humans. Therefore, osteochondral cores (4-8 mm) were obtained from the medial and lateral femoral condyles of equine and human donors. Cores were processed for histology and for biochemical quantification of DNA, glycosaminoglycan (GAG) and collagen content. Equine and human osteochondral tissues possess similar geometrical (thickness) and organizational (GAG, collagen and DNA distribution with depth) features. These comparable trends further underscore the validity of the equine model for the evaluation of regenerative approaches for articular cartilage. PMID- 22781207 TI - Combined pulmonary fibrosis and emphysema in connective tissue disease. AB - PURPOSE OF REVIEW: This review discusses combined pulmonary fibrosis and emphysema (CPFE) in the setting of connective tissue disease. RECENT FINDINGS: CPFE is a recently identified syndrome in smokers or ex-smokers characterized by dyspnea often severe, preserved lung volumes, severely impaired gas exchanges, and an increased risk of pulmonary hypertension associated with a dismal prognosis, and possibly lung cancer. It may be encountered in the setting of connective tissue diseases, especially rheumatoid arthritis and systemic sclerosis, with generally similar features as 'idiopathic' (tobacco-related) CPFE. The diagnosis is based on the presence of both emphysema predominating in the upper lobes and frequently paraseptal, and interstitial abnormalities suggesting pulmonary fibrosis in the lower lung zones with velcro crackles at auscultation. Pathologic radiological correlations are difficult owing to various pathology and difficulties in identifying honeycombing at chest high-resolution computed tomography in the setting of coexistent emphysema. Tobacco smoking is associated with an increased risk of developing most of the individual components of the syndrome (i.e. emphysema, pulmonary fibrosis, pulmonary hypertension, rheumatoid arthritis, and pulmonary fibrosis among patients with rheumatoid arthritis). CPFE impacts modalities of follow-up for pulmonary function and detection of pulmonary hypertension especially in systemic sclerosis. SUMMARY: The syndrome of CPFE is a distinct pulmonary manifestation in the spectrum of lung diseases associated with connective tissue diseases, especially in smokers or ex-smokers. PMID- 22781208 TI - Diagnosing idiopathic pulmonary fibrosis: to biopsy or not to biopsy. PMID- 22781209 TI - Familial forms of nonspecific interstitial pneumonia/idiopathic pulmonary fibrosis: clinical course and genetic background. AB - PURPOSE OF REVIEW: Familial pulmonary fibrosis has long been recognized and suggests that pulmonary fibrosis may have a genetic origin in some cases with an autosomal dominant transmission. RECENT FINDINGS: Mutations in the telomerase complex and in the surfactant pathways have been discovered in the last decade. Almost 20% of the cases of familial pulmonary fibrosis are related to known functional mutations in one of these systems. A polymorphism in the promoter of the MUC5B gene has been associated with both sporadic and familial forms of idiopathic pulmonary fibrosis; however, the impact of this association remains to be determined. SUMMARY: These genes point to alveolar epithelium injury and repair as a major component of the fibrotic process. PMID- 22781211 TI - Meniscal pullout repair following meniscal ossicle resection: a case report. AB - We present this case of a meniscal ossicle of the posterior horn of the medial meniscus that was treated by an arthroscopic ossicle resection followed by a pullout repair of the remaining meniscus. A 49-year-old businessman complained of catching and left knee pain. Radiographic and arthroscopic findings revealed a meniscal ossicle embedded in the posterior horn of the medial meniscus and posterior horn tear. After resection of the posterior horn with the ossicle, a pullout suture repair for the posterior segment of the meniscus was done to minimize the further extrusion of the meniscus. A histologic appearance supported the vestigial development of the meniscal ossicle as the etiology. This is the first report describing a repair of the meniscus after ossicle resection. PMID- 22781212 TI - Sensory-based and higher-order operations contribute to abnormal emotional prosody processing in schizophrenia: an electrophysiological investigation. AB - BACKGROUND: Schizophrenia is characterized by deficits in emotional prosody (EP) perception. However, it is not clear which stages of processing prosody are abnormal and whether the presence of semantic content contributes to the abnormality. This study aimed to examine event-related potential (ERP) correlates of EP processing in 15 chronic schizophrenia individuals and 15 healthy controls. METHOD: A total of 114 sentences with neutral semantic content [sentences with semantic content (SSC) condition] were generated by a female speaker (38 with happy, 38 with angry, and 38 with neutral intonation). The same sentences were synthesized and presented in the 'pure prosody' sentences (PPS) condition where semantic content was unintelligible. RESULTS: Group differences were observed for N100 and P200 amplitude: patients were characterized by more negative N100 for SSC, and more positive P200 for angry and happy SSC and happy PPS. Correlations were found between delusions and P200 amplitude for happy SSC and PPS. Higher error rates in the recognition of EP were also observed in schizophrenia: higher error rates in neutral SSC were associated with reduced N100, and higher error rates in angry SSC were associated with reduced P200. CONCLUSIONS: These results indicate that abnormalities in prosody processing occur at the three stages of EP processing, and are enhanced in SSC. Correlations between P200 amplitude for happy prosody and delusions suggest a role that abnormalities in the processing of emotionally salient acoustic cues may play in schizophrenia symptomatology. Correlations between ERP and behavioral data point to a relationship between early sensory abnormalities and prosody recognition in schizophrenia. PMID- 22781213 TI - Adherence to ATLS primary and secondary surveys during pediatric trauma resuscitation. AB - STUDY AIM: Adherence to Advanced Trauma Life Support (ATLS) protocol has been associated with improved management of injured patients. The objective of this study is to determine factors associated with delayed and omitted ATLS primary and secondary survey tasks at a level 1 pediatric trauma center. METHODS: Video recorded resuscitations of 237 injured patients <18 years old obtained over a four month period at our hospital were evaluated to assess completeness and timeliness of essential tasks in the primary and secondary survey of ATLS. Multivariate analyses were performed to identify features associated with decreased ATLS performance. RESULTS: Primary survey findings were stated less often in patients with burn injuries compared to those with blunt injuries (RR=1.72; 95% CI: 1.26-2.35) and less often during the overnight shift [11 PM-7 AM] (RR=1.22; 95% CI: 1.02-1.46). Secondary survey findings were verbalized less often in patients with penetrating injures (RR=2.30; 95% CI: 1.06-5.00). Time to statement of primary surveys findings was delayed in patients with burn injuries (HR=0.69; 95% CI: 0.48-0.98) and among those transferred from another hospital. Completeness and timeliness of ATLS task performance were not associated with age or injury severity score. CONCLUSIONS: Mechanism of injury and hospital factors are associated with incomplete and delayed primary and secondary surveys. Interventions that address deficient ATLS adherence related to these factors may lead to a reduction in errors during this critical period of patient care. PMID- 22781214 TI - Factors predicting doctors' reporting of performance change in response to multisource feedback. AB - BACKGROUND: Multi-source feedback (MSF) offers doctors feedback on their performance from peers (medical colleagues), coworkers and patients. Researchers increasingly point to the fact that only a small majority of doctors (60-70 percent) benefit from MSF. Building on medical education and social psychology literature, the authors identified several factors that may influence change in response to MSF. Subsequently, they quantitatively studied the factors that advance the use of MSF for practice change. METHODS: This observational study was set in 26 non-academic hospitals in the Netherlands. In total, 458 specialists participated in the MSF program. Besides the collation of questionnaires, the Dutch MSF program is composed of a reflective portfolio and a facilitative interview aimed at increasing the acceptance and use of MSF. All specialists who finished a MSF procedure between May 2008 and September 2010 were invited to complete an evaluation form. The dependent variable was self-reported change. Three categories of independent variables (personal characteristics, experiences with the assessments and mean MSF ratings) were included in the analysis. Multivariate regression analysis techniques were used to identify the relation between the independent variables and specialists' reported change in actual practice. RESULTS: In total, 238 medical specialists (response rate 52 percent) returned an evaluation form and participated in the study. A small majority (55 percent) of specialists reported to have changed their professional performance in one or more aspects in response to MSF. Regression analyses revealed that two variables had the most effect on reported change. Perceived quality of mentoring positively influenced reported change (regression coefficient beta = 0.527, p < 0.05) as did negative scores offered by colleagues. (regression coefficient beta = -0.157, p < 0.05). The explained variance of these two variables combined was 34 percent. CONCLUSIONS: Perceived quality of mentoring and MSF ratings from colleagues seem to be the main motivators for the self-reported change in response to MSF by specialists. These insights could leverage in increasing the use of MSF for practice change by investing in the quality of mentors. PMID- 22781215 TI - Pseudohypoxemia in a patient with chronic lymphocytic leukemia. PMID- 22781216 TI - Harnessing the power of human tumor-derived cell lines for the rational design of cancer therapies. PMID- 22781217 TI - Doppler echocardiography does not accurately estimate pulmonary artery systolic pressure in HIV-infected patients. AB - Doppler echocardiography is used to screen for HIV-related pulmonary arterial hypertension (HRPAH). We studied patients with HIV infection to determine the accuracy of Doppler echocardiography-estimated pulmonary artery systolic pressure (PASP) compared with PASP measured during right heart catheterization. Doppler echocardiography-estimated PASP was inaccurate in 19.7% of cases. Using Doppler echocardiography-estimated PASP, one in three patients with HRPAH was missed. Doppler echocardiography estimates of PASP are not accurate in patients with HIV. PMID- 22781219 TI - Increasing sexual risk behaviour among Dutch men who have sex with men: mathematical models versus prospective cohort data. AB - Changes in risk behaviour among men who have sex with men (MSM) in the Netherlands were estimated by fitting a mathematical model to annual HIV and AIDS diagnoses in the period 1980-2009 and, independently, from rates of unprotected anal intercourse in a prospective cohort study in Amsterdam. The agreement between the two approaches was very good, confirming that in terms of incidence, increasing risk behaviour between MSM is offsetting benefits offered by enhanced testing and treatment. PMID- 22781218 TI - Transient elastography to rule out esophageal varices and portal hypertensive gastropathy in HIV-infected individuals with liver cirrhosis. AB - BACKGROUND/AIMS: It is recommended that patients with cirrhosis undergo endoscopic screening to rule out the presence of gastroesophageal varices: a noninvasive predictive method to identify cirrhotic patients with a very low risk of esophageal varices could potentially avoid unnecessary endoscopies. METHODS: We studied in 85 HIV-infected patients with cirrhosis the association between the absence of esophageal varices and portal hypertensive gastropathy, assessed by endoscopy, and liver stiffness measurement by transient elastography. We analyzed other parameters related to portal hypertension and hepatic function. RESULTS: Values of transient elastography and platelet count were significantly associated with absence of esophageal varices/portal hypertensive gastropathy. The area under the receiver operating characteristics curve [95% confidence interval (CI)] of transient elastography for the prediction of the absence of esophageal varices/portal hypertensive gastropathy was 0.7 (0.58-0.81). A liver stiffness measurement value less than 20 kPa was highly predictive of the absence of esophageal varices and portal hypertensive gastropathy. The combination of transient elastography (<20 kPa) and platelet count (>120 * 10 cells/l) had the highest negative predictive value (100%, CI 95% 77.2-100) for absence of esophageal varices and portal hypertensive gastropathy. CONCLUSION: Transient elastography combined with platelet count is useful for predicting the absence of esophageal varices and portal hypertensive gastropathy and, therefore, avoid unnecessary diagnostic endoscopies in HIV-infected patients with liver cirrhosis. PMID- 22781220 TI - Central nervous system-immune reconstitution inflammatory syndrome in resource limited settings: current burden and future needs. PMID- 22781221 TI - The epidemiological impact and cost-effectiveness of HIV testing, antiretroviral treatment and harm reduction programs. AB - OBJECTIVES: To estimate trends in the HIV epidemic in China, and explore the epidemiological impact and cost-effectiveness of expanded voluntary counseling and testing (VCT), antiretroviral treatment (ART), and harm reduction programs in preventing the spread of HIV. DESIGN AND METHODS: A mathematical model was developed and calibrated to reflect the dynamics of disease progression and transmission through sexual contacts and needle sharing in China, and the cost effectiveness of four interventions was analyzed. Multivariate sensitivity analysis was used to estimate uncertainty ranges for all outcomes. RESULTS: A total of 3.4 million new HIV infections were estimated to occur over the next 30 years if no preventive measures were implemented, of which 75% will occur in high risk groups, such as injecting drug users (IDUs) and men who have sex with men. Expanding ART treatment is most cost-effective, at 4840 (uncertainty range/UR: 3960-5980) international dollars per quality-adjusted life year gained. The optimal cost-effectiveness path is from ART to the combination strategy of ART and harm reduction, followed by the combination strategy of harm reduction, ART and VCT. CONCLUSION: Expanded VCT (low-risk once, high-risk annually), expanded ART, harm reduction programs and all combinations of these strategies are cost effective relative to the base case. In order to bring China to a lower phase of the HIV epidemic, in addition to VCT and ART treatment, efforts in reducing risk behavior will be necessary. PMID- 22781223 TI - Trends in mortality according to hepatitis C virus serostatus in the era of combination antiretroviral therapy. AB - OBJECTIVE: To study trends in overall deaths and cause-specific deaths stratified by hepatitis C virus (HCV) serostatus in a cohort of combination antiretroviral (cART)-naive HIV-infected patients in Spain. METHODS: We analyzed data from 1997 to 2008 in two calendar periods: 1997-2003 and 2004-2008. Deaths were ascertained through cohort reporting and a cross-match with the Spanish National Death Index. We used Poisson regression to model mortality rates and risk factors. RESULTS: We analyzed 5974 HIV-positive cART-naive patients: 2471 (1497 HCV positive) in the period 1997-2003, and 3503 (689 HCV positive) in the period 2004-2008. A total of 232 deaths (158 during the first period, and 74 during the second period) were detected during 19 416 person-years of follow-up; the death rate was 12.9 of 1000 person-years. Crude overall death rates [95% confidence interval (CI)] were 16.5 (14.2-19.1) in 1997-2003 and 8.5 (6.7-10.6) in 2004-2008. The incidence rate ratio (IRR) (95%CI) in 2004-2008 taking 1997-2003 as a reference was 0.51 (0.39 0.67). When we stratified by HCV serostatus, the overall death IRR (95% CI) taking 1997-2003 as reference was 0.52 (0.32-0.85) for HCV-negative patients and 1.27 (0.90-1.79) for HCV-positive patients. When we considered cause-specific deaths (liver-related, AIDS-related, and nonliver-related/non-AIDS-related), findings were similar to those for overall-deaths. CONCLUSION: Taking the first years of the cART era as a reference, we observed a decrease in overall and cause specific mortality. This decrease was only observed in HCV-negative patients. PMID- 22781224 TI - Ribavirin and abacavir drug interaction in HIV-HCV coinfected patients: fact or fiction? AB - OBJECTIVE(S): To examine the impact of ribavirin and abacavir coadministration on hepatitis C virus (HCV) virological response and trough ribavirin plasma concentration (Cmin) in HIV-HCV coinfected patients. DESIGN: Pharmacokinetic substudy on patients from the ANRS CO-13 HEPAVIH cohort. METHODS: Patients receiving ribavirin-pegylated interferon for whom a ribavirin steady state Cmin was prospectively determined were included. Rapid virological response (RVR), early virological response (EVR) and sustained virological response (SVR) as well as HCV-RNA decline were evaluated. RESULTS: Overall, 124 HIV-HCV coinfected patients (95% on antiretroviral therapy) were enrolled. Of these patients, 22% received abacavir. The overall median (interquartile range) ribavirin Cmin was 1.6 mg/l (1.2-2.2) with no statistical difference between abacavir users and nonusers [1.5 mg/l (0.99-2.1) and 1.7 (1.2-2.3), P = 0.15]. RVR and EVR were 52 and 72%, respectively. There was no difference observed in the proportion of abacavir users vs. nonusers achieving RVR (respectively 59 vs. 50%, P = 0.40) or EVR (72 vs. 73%, P = 0.94), or in the HCV-RNA decline at week 4 [-2.24 log(10) IU/ml, (-3.58; -0.81) and -1.27 (-2.8; -0.47) P = 0.28] or at week 12 [-1.76 log(10) IU/ml (-3.67; -0.35) and -1.85 (-3.13; -1.13) (P = 0.58)]. The SVR rate was 45% for abacavir users and 24% for abacavir nonusers, but the difference was not statistically significant (P = 0.059). CONCLUSION: In our study, there was no evidence that abacavir affected HCV treatment outcomes and the ribavirin Cmin was similar in abacavir users and nonusers, confirming the absence of pharmacokinetic interaction between abacavir and ribavirin. An abacavir-containing regimen is, therefore, a well tolerated treatment alternative for coinfected patients starting HCV treatment. PMID- 22781225 TI - Natural killer cell function in women at high risk for HIV acquisition: insights from a microbicide trial. AB - OBJECTIVE: To assess the role of natural killer (NK) cells in HIV acquisition. DESIGN: We conducted a nested case-control substudy to the Center for the AIDS Programme of Research in South Africa (CAPRISA004) tenofovir gel trial. METHODS: Thirty women who acquired HIV infection (cases) and 30 women with high-risk sexual activity who remained HIV-negative (controls) were selected. Proliferation, degranulation and interferon-gamma (IFNgamma) secretion were measured by multiparametric flow cytometry after culture of recombinant human interleukin-2 (rhIL-2)-activated peripheral blood mononuclear cells with 721.221 cells or in-vitro HIV-infected, autologous CD4 T-cell blasts. Relationships between pre-acquisition NK cell responses and HIV acquisition were modeled with logistic regression models. RESULTS: NK cells from cases had lower IFNgamma responses to human leukocyte antigen-deficient 721.221 cells than controls (median %IFNgammaposNK cells: 13.7 vs. 21.6%, P = 0.03). rhIL-2-activated NK cells from cases had responses to autologous HIV-infected target cells distinct from controls: cases had fewer proliferating and more frequent degranulating NK cells. NK cells from cases had significantly lower IFNgamma responses to in-vitro HIV-infected autologous T cells than controls even after adjusting for responses to uninfected blasts (median %IFNgammaposNK-cells: 0.53 vs. 2.09%, P = 0.007). Responses to in-vitro HIV-infected autologous T cells were significantly lower in herpes simplex virus 2 (HSV-2)-infected women (P = 0.003). IFNgamma NK cell responses to autologous HIV-infected cells were associated with lower risk of HIV acquisition (odds ratio adjusted for age, gel arm, HSV-2 and immune activation: 0.582, 95% confidence interval 0.347-0.977, P = 0.04). CONCLUSION: At the time of exposure to HIV, women with impaired NK cell IFNgamma responses were more likely to acquire HIV infection. NK cells, as early responders to viral exposure, were associated with lower risk of HIV acquisition, independent of the intercalated effect of HSV-2 infection suppressing NK cell responses. PMID- 22781222 TI - Hepatitis C virus viremia increases the incidence of chronic kidney disease in HIV-infected patients. AB - BACKGROUND: Several studies have reported on an association between hepatitis C virus (HCV) antibody status and the development of chronic kidney disease (CKD), but the role of HCV viremia and genotype are not well defined. METHODS: Patients with at least three serum creatinine measurements after 1 January 2004 and known HCV antibody status were included. Baseline was defined as the first eligible estimated glomerular filtration rate (eGFR) (Cockcroft-Gault equation), and CKD was either a confirmed (>3 months apart) eGFR of 60 ml/min per 1.73 m or less for patients with a baseline eGFR more than 60 ml/min per 1.73 m or a confirmed 25% decline in eGFR for patients with a baseline eGFR of 60 ml/min per 1.73 m or less. Incidence rates of CKD were compared between HCV groups (anti-HCV-negative, anti-HCV-positive with or without viremia) using Poisson regression. RESULTS: Of 8235 patients with known anti-HCV status, 2052 (24.9%) were anti-HCV-positive of whom 983 (47.9%) were HCV-RNA-positive, 193 (9.4%) HCV-RNA-negative and 876 (42.7%) had unknown HCV-RNA. At baseline, the median eGFR was 97.6 (interquartile range 83.8-113.0) ml/min per 1.73 m. During 36123 person-years of follow-up (PYFU), 495 patients progressed to CKD (6.0%) with an incidence rate of 14.5 per 1000 PYFU (95% confidence interval 12.5-14.9). In a multivariate Poisson model, patients who were anti-HCV-positive with HCV viremia had a higher incidence rate of CKD, whereas patients with cleared HCV infection had a similar incidence rate of CKD compared with anti-HCV-negative patients. There was no association between CKD and HCV genotype. CONCLUSION: Compared with HIV-monoinfected patients, HIV positive patients with chronic rather than cleared HCV infection were at increased risk of developing CKD, suggesting a contribution from active HCV infection toward the pathogenesis of CKD. PMID- 22781226 TI - A new method to assign country of HIV infection among heterosexuals born abroad and diagnosed with HIV. AB - OBJECTIVE: To apply a new method to ascertain likely place of HIV infection among persons born abroad and diagnosed with HIV in the United Kingdom (UK). DESIGN: Analyses of heterosexual adults born abroad, diagnosed with HIV in the UK between 2004 and 2010, and reported to the national HIV diagnoses database. METHODS: Year of infection was ascertained by applying an estimated rate of CD4 cell count decline between an individual's CD4 cell count at diagnosis and estimates of CD4 cell count at infection. A person was classified as having probably acquired HIV while living in the UK if estimated year of infection was later than reported year of arrival in the UK. RESULTS: Of 10 612 heterosexual adults born abroad included in the analyses, 85% (9065) were of black-African ethnicity. We estimate that 33% (26-39%) of persons acquired HIV while living in the UK. This percentage increased from 24% (16-39%) in 2004 to 46% (31-50%) in 2010 (P < 0.01). The estimate of 33% is three times higher than national estimates of HIV acquired in the UK based on clinic reports (11%) (P < 0.01). CONCLUSION: : Assigning place of HIV infection using routinely available clinical and demographic data and estimated rates of CD4 cell decline is feasible. We report a high and increasing proportion of persons born abroad who appear to have acquired their HIV infection while living in the UK. These findings highlight the need for continued targeted HIV prevention efforts, particularly among black-African communities. PMID- 22781227 TI - Risk factors, barriers and facilitators for linkage to antiretroviral therapy care: a systematic review. AB - OBJECTIVE: To characterize patient and programmatic factors associated with retention in care during the pre-antiretroviral therapy (ART) period and linkage to ART care. DESIGN: Systematic literature review. METHODS: An electronic search was conducted on MEDLINE, Global Health, Google Scholar and conference databases to identify studies reporting on predictors, barriers and facilitators of retention in care in the pre-ART period, and linkage to care at three steps: ART eligibility assessment, pre-ART care and ART initiation. Factors associated with attrition were then divided into areas for intervention. RESULTS: Seven hundred and sixty-eight citations were identified. Forty-two studies from 12 countries were included for review, with the majority from South Africa (16). The most commonly cited category of factors was transport costs and distance. Stigma and fear of disclosure comprised the second most commonly cited category of factors followed by staff shortages, long waiting times, fear of drug side effects, male sex, younger age and the need to take time off work. CONCLUSION: This review highlights the importance of investigating interventions that could reduce transport difficulties. Decentralization, task-shifting and integration of services need to be expedited to alleviate health system barriers. Patient support groups and strategic posttest counselling are essential to assist patients deal with stigma and disclosure. Moreover, well tolerated first-line drugs and treatment literacy programmes are needed to improve acceptance of ART. This review suggests a combination of interventions to retain specific groups at risk for attrition such as workplace programmes for employed patients, dedicated clinic and support programmes for men and younger individuals. PMID- 22781229 TI - Spatial uniformity inspection apparatus for solar cells using a projection display. AB - We demonstrate a measurement apparatus to inspect spatial uniformity of quantum efficiency of solar cells using a beam projector. Deviation of irradiance from the used beam projector over the area of 1.5*0.8 m on the cell plane was flattened within +/-2.6% through gray scale adjustment, which was originally about 200%. Scanning a small square image with an area of 3*3 mm over a square shaped photovoltaic cell with an area of 15.6*15.6 cm, we could identify the locations according to efficiency level and showed that the cell had quantum efficiency deviation of more than 10%. Utilizing the advantageous feature of a projection display, we also demonstrated that this apparatus can inspect the spatial uniformity of solar modules and panels consisting of multiple solar cells. PMID- 22781230 TI - Physical mechanism underlying temperature effects on phase retardation. AB - We report on the physical mechanism underlying the temperature dependence of phase retardation. Changes in refractive index and thickness of the wave plate are the two main contributions to phase retardation variations. Temperature dependent changes in refractive index are described by Sellmeier's equation. Constants in this equation need to be determined by fits to experimental data. A new high-precision instrument was used to measure phase retardation at various temperatures. Once determined, the fitting equation can be used to calculate the phase retardation at any temperature, and thus has implications for wave-plate industrial manufacturing. PMID- 22781231 TI - Numerical and experimental investigation on Ag+-Na+ field assisted ion-exchanged channel waveguides. AB - The characteristics of Ag+ diffusion during field assisted fabrication of a channel waveguide in glass substrates are analyzed using a numerical model. Differences between the results of the author's original model and the other typically used models are discussed. Experimental conditions have been chosen to clearly demonstrate the essential features of Ag+ concentration contours, particularly near the mask edges. Metallic and dielectric masks have been used in the experiment, and the results are similar for both mask materials. The shapes of Ag+ concentration contours reveal the presence of a thin polarized layer under the mask and seem to be consistent with the results predicted by the proposed numerical model. Some modifications of the model are suggested for a better fit of the numerical to the experimental results. PMID- 22781232 TI - Experimental validation of a simple approximation to determine the linewidth of a laser from its frequency noise spectrum. AB - Laser frequency fluctuations can be characterized either comprehensively by the frequency noise spectrum or in a simple but incomplete manner by the laser linewidth. A formal relation exists to calculate the linewidth from the frequency noise spectrum, but it is laborious to apply in practice. We recently proposed a much simpler geometrical approximation applicable to any arbitrary frequency noise spectrum. Here we present an experimental validation of this approximation using laser sources of different spectral characteristics. For each of them, we measured both the frequency noise spectrum to calculate the approximate linewidth and the actual linewidth directly. We observe a very good agreement between the approximate and directly measured linewidths over a broad range of values (from kilohertz to megahertz) and for significantly different laser line shapes. PMID- 22781233 TI - Terahertz modulator based on insulator-metal transition in photonic crystal waveguide. AB - A terahertz modulator based on the insulator-metal transition (IMT) in a photonic crystal waveguide (PCW) coated by vanadium dioxide (VO2) film is proposed. The numerical simulations show that a dielectric state and a metallic state with quite different photonic band structures and transmission properties in the proposed PCW are reciprocally converted because of the IMT of VO2, and the pass bands of this PCW are greatly shifted from 0.68 to 0.8 and 1.02 to 1.25 THz to 0.8-1.45 THz. This PCW significantly enhances the modulation depth and sensitivity compared with bare VO2 film. Extensive investigation demonstrates that the thickness of VO2 film greatly affects the IMT process in the PCW, and limits the ultimate modulation depth of the device. The proposed modulation scheme will be of great significance for potential THz applications. PMID- 22781234 TI - Diffractive-refractive correction units for plastic compact zoom lenses. AB - A method of designing a plastic zoom lens with a diffractive-refractive hybrid corrector, comprising one diffractive lens and one refractive lens, is described. The efficiency of this method is demonstrated by designing a compact zoom lens for a mobile phone. This zoom design, incorporating lenses made only of two commercial optical plastics (polymethylmethacrylate and polycarbonate), provides high optical performance. PMID- 22781228 TI - The impact of HAART on cardiomyopathy among children and adolescents perinatally infected with HIV-1. AB - OBJECTIVE: Previous studies of cardiomyopathy among children perinatally infected with HIV were conducted before the routine use of HAART. Nucleoside analogs [nucleoside reverse transcriptase inhibitors (NRTIs)], the backbone of HAART, have been associated with mitochondrial toxicity, which can lead to cardiomyopathy. We evaluated the association of HAART and specific NRTIs associated with mitochondrial toxicity, on development of cardiomyopathy among perinatally HIV-infected children. DESIGN: Three thousand and thirty-five perinatally HIV-infected children enrolled in a US-based multicenter prospective cohort study were followed for cardiomyopathy, defined as a clinical diagnosis or initiation of digoxin, from 1993 to 2007. METHODS: Cox models were used to estimate the effects of HAART and NRTIs on cardiomyopathy, identify predictors of cardiomyopathy among HAART users, and estimate the association between development of cardiomyopathy and mortality. RESULTS: Ninety-nine cases of cardiomyopathy were identified over follow-up (incidence rate: 5.6 cases per 1000 person-years) at a median age of 9.4 years. HAART was associated with a 50% lower incidence of cardiomyopathy compared with no HAART use (95% confidence interval: 20%, 70%). Zalcitabine (ddC) use, however, was associated with an 80% higher incidence of cardiomyopathy. Among HAART users, older age at HAART initiation, ddC use before HAART initiation, initiating a HAART regimen containing zidovudine (ZDV), and a nadir CD4 percentage less than 15% were independently associated with a higher rate of cardiomyopathy. Cardiomyopathy was associated with a six fold higher mortality rate. CONCLUSION: HAART has dramatically decreased the incidence of cardiomyopathy among perinatally HIV-infected children. However, they remain at increased risk for cardiomyopathy and ongoing ZDV exposure may increase this risk. PMID- 22781235 TI - Concentration measurement of NO using self-absorption spectroscopy of the gamma band system in a pulsed corona discharge. AB - Nitric oxide (NO) concentrations were measured using the gamma band system spectrum based on the strong self-absorption effect of NO in pulsed corona discharges. The radiative transitional intensities of the NO gamma band were simulated based on the theory of molecular spectroscopy. The intensities of some bands, especially gamma(0,0) and gamma(1,0), are weakened by the self-absorption. The correlations between the spectral self-absorption intensities and NO concentration were validated using a modified Beer-Lambert law with a combined factor K relating the branching ratio and the NO concentration, and a nonlinear index alpha that is applicable to the broadband system. Optical emissive spectra in pulsed corona discharges in NO and N2/He mixtures were used to evaluate the two parameters for various conditions. Good agreement between the experimental and theoretical results verifies the self-absorption behavior seen in the UV spectra of the NO gamma bands. PMID- 22781236 TI - Quantitative elemental analysis of steel using calibration-free laser-induced breakdown spectroscopy. AB - We report the quantitative elemental analysis of a steel sample using calibration free laser-induced breakdown spectroscopy (CF-LIBS). A Q-switched Nd:YAG laser (532 nm wavelength) is used to produce a plasma by focusing it onto a steel sample in air at atmospheric pressure. The time-resolved spectra from atomic and ionic emission lines of the steel elements are recorded by an echelle grating spectrograph coupled with a gated intensified CCD camera and are used for the plasma characterization and quantitative analysis of the sample. The time delay at which the plasma is in local thermodynamic equilibrium as well as optically thin, necessary for elemental analysis, is deduced. An algorithm for the CF-LIBS relating the experimentally measured spectral intensity values with the basic physics of the plasma is developed and used for the determination of Fe, Cr, Ni, Mg, and Si concentrations in the steel sample. The analytical results obtained from the CF-LIBS technique agree well with the certified values of the elements in the sample, with relative uncertainties of less than 5%. PMID- 22781237 TI - Extension of the Norton-Beer apodizing functions in Fourier transform spectrometry. AB - Apodization is a mathematical tool used in Fourier transform spectrometry to reduce the spurious oscillation in the output spectrum. We investigate Norton Beer apodizing functions and take advantage of the main series to introduce a family of new functions. They weigh the interferogram to zero continuously within the same optical path difference and, accordingly, improve the convergence property of the instrumental line shape (ILS) for the apodized spectrum. In the meantime, the range of spectral smearing is well reduced. Compared with the Norton-Beer functions, the new functions are more flexible in practice and are more applicable with regard to distinguishing the spectral lines, especially the weak lines, which are not too close to the center of a strong line but are still susceptible to the ringing of ILS. PMID- 22781239 TI - Toward the diffraction limit with transmissive x-ray lenses in astronomy. AB - We develop an analytical approach to refractive, blazed diffractive, and achromatic x-ray lenses of scalable dimensions for energies from 1 to 20 keV. Based on the parabolic wave equation, their wideband imaging properties are compared and optimized for a given spectral range. Low-Z lens materials for massive cores and rugged alternatives, such as polycarbonate or Si for flat Fresnel components, are investigated with respect to their suitability for diffraction-limited high-energy astronomy. Properly designed "hybrid" combinations can serve as an approach to x-ray telescopes with an enhanced efficiency throughout the whole considered band, nearly regardless of their inherent absorption. PMID- 22781238 TI - Monte Carlo model of the penetration depth for polarization gating spectroscopy: influence of illumination-collection geometry and sample optical properties. AB - Polarization-gating has been widely used to probe superficial tissue structures, but the penetration depth properties of this method have not been completely elucidated. This study employs a polarization-sensitive Monte Carlo method to characterize the penetration depth statistics of polarization-gating. The analysis demonstrates that the penetration depth depends on both the illumination collection geometry [illumination-collection area (R) and collection angle (theta(c))] and on the optical properties of the sample, which include the scattering coefficient (MU(s)), absorption coefficient (MU(a)), anisotropy factor (g), and the type of the phase function. We develop a mathematical expression relating the average penetration depth to the illumination-collection beam properties and optical properties of the medium. Finally, we quantify the sensitivity of the average penetration depth to changes in optical properties for different geometries of illumination and collection. The penetration depth model derived in this study can be applied to optimizing application-specific fiber optic probes to target a sampling depth of interest with minimal sensitivity to the optical properties of the sample. PMID- 22781240 TI - Intracavity absorption spectroscopy with a tunable multimode traveling-wave ring Ti:sapphire laser. AB - A tunable multimode unidirectional traveling-wave Ti:sapphire laser was developed to measure in situ the atmospheric absorption spectra using intracavity absorption spectroscopy. The effective absorption path length was 2100 km. O2 and H2O vapor lines in atmosphere with absorption coefficients of 10(-6)-10(-8) cm( 1) were measured with uncertainties <5%, and the absorption coefficients were in agreement with those estimated from the HITRAN database. By tuning the wavelength, a weak absorption line with an absorption coefficient of 10(-9) cm( 1) was measured with a sensitivity of 2*10(-10) cm(-1). The sensitivity was limited by the residual parasitic variation that appeared in the spectrum. PMID- 22781241 TI - Digital video steganalysis using motion vector recovery-based features. AB - As a novel digital video steganography, the motion vector (MV)-based steganographic algorithm leverages the MVs as the information carriers to hide the secret messages. The existing steganalyzers based on the statistical characteristics of the spatial/frequency coefficients of the video frames cannot attack the MV-based steganography. In order to detect the presence of information hidden in the MVs of video streams, we design a novel MV recovery algorithm and propose the calibration distance histogram-based statistical features for steganalysis. The support vector machine (SVM) is trained with the proposed features and used as the steganalyzer. Experimental results demonstrate that the proposed steganalyzer can effectively detect the presence of hidden messages and outperform others by the significant improvements in detection accuracy even with low embedding rates. PMID- 22781243 TI - Approaching ultimate resolution for soft x-ray spectrometers. AB - We explore the potential performance of soft x-ray spectrometers based on the use of varied-line-spacing spherical diffraction gratings (VLS-SG). The quantitative assessment is based on an optimization procedure to obtain both negligible optical aberrations at full illumination of the grating and a quasi linear focal curve. It involves high-order optical aberration cancellation to calculate the focal curves. We also examine the validity of small divergence closed-form formulas describing the light path function. Optimizing the optical and geometric parameters gives an ultimate resolving power, at 930 eV, of between 10,800 for a 3 m long instrument and 34,000 for an 11 m spectrometer according to the Rayleigh criterion. Typical fabrication tolerances would scale these values down by about 10%. The findings are validated by ray-tracing simulations. PMID- 22781244 TI - Design and scaling of monocentric multiscale imagers. AB - Monocentric multi-scale (MMS) lenses are a new approach to high-resolution wide angle imaging, where a monocentric objective lens is shared by an array of identical rotationally symmetric secondary imagers that each acquire one overlapping segment of a mosaic. This allows gigapixel images to be computationally integrated from conventional image sensors and relatively simple optics. Here we describe the MMS design space, introducing constraints on image continuity and uniformity, and show how paraxial system analysis can provide both volume scaling and a systematic design methodology for MMS imagers. We provide the detailed design of a 120 degrees field of viewimager (currently under construction) resolving 2 gigapixels at 41.5 MUrad instantaneous field of view, and demonstrate reasonable agreement with the first-order scaling calculation. PMID- 22781242 TI - Microelectromechanical systems scanning-mirror-based handheld probe for fluorescence molecular tomography. AB - A novel handheld probe based on a microelectromechanical systems (MEMS) scanning mirror for three-dimensional (3D) fluorescence molecular tomography (FMT) is described. The miniaturized probe consists of a MEMS mirror for delivering an excitation light beam to multiple preselected points at the tissue surface and an optical fiber array for collecting the fluorescent emission light from the tissue. Several phantom experiments based on indocyanine green, an FDA approved near-infrared (NIR) fluorescent dye, were conducted to assess the imaging ability of this device. Tumor-bearing mice with systematically injected tumor-targeted NIR fluorescent probes were scanned to further demonstrate the ability of this MEMS-based FMT for imaging small animals. PMID- 22781245 TI - Chromatic dispersion correction in planar waveguide using one-layer volume holograms based on three-step exposure. AB - We propose a novel method to correct the chromatic dispersion in a planar waveguide with volume holograms fabricated by the three-step exposure technique. The 532 nm green laser is used to illuminate the holographic plate in three groups of different angles for achieving the desired holograms. When it is used in the planar waveguide, the chromatic dispersion of the original display can be corrected and an image with the real color can be obtained. The experiments are performed, and the results are in good agreement with the theory. It is believed that this technique is a good way to correct the chromatic problems in the display systems in the future. PMID- 22781246 TI - Analysis of ultrasonic frequency response of surface attached fiber Bragg grating. AB - In recent years, fiber Bragg grating (FBG), for the well-known advantages over other fiber optic sensors, has attracted more attention in ultrasonic inspection for structure health monitoring (SHM). Spectrum shift of FBG to ultrasonic wave is caused by the refractive index profile changing along the FBG, which can be attributed to nonuniform perturbation caused by strain-optic and geometric effects of ultrasonic wave. Response of FBG to the above two effects was analyzed firstly by the V-I transmission matrix model, showing high computing efficiency. Based on this model, spectra response of FBG under changing ultrasonic frequencies was simulated and discussed. In experiment, the system was able to detect a wideband ultrasonic wave ranging from 15 to 1380 kHz. These results would provide a guideline for an FBG-based acoustic detection system design in a specific ultrasonic frequency. PMID- 22781247 TI - Refractive index and temperature sensitivity characteristics of a micro-slot fiber Bragg grating. AB - Fabrication and characterization of a UV inscribed fiber Bragg grating (FBG) with a micro-slot liquid core is presented. Femtosecond (fs) laser patterning/chemical etching technique was employed to engrave a micro-slot with dimensions of 5.74 MUm(h)*125 MUm(w)*1388.72 MUm(l) across the whole grating. The device has been evaluated for refractive index (RI) and temperature sensitivities and exhibited distinctive thermal response and RI sensitivity beyond the detection limit of reported fiber gratings. This structure has not just been RI sensitive, but also maintained the robustness comparing with the bare core FBGs and long-period gratings with the partial cladding etched off. PMID- 22781248 TI - Numerical study on an application of subwavelength dielectric gratings for high sensitivity plasmonic detection. AB - Although subwavelength dielectric gratings can be employed to achieve a high sensitivity of the surface plasmon resonance (SPR) biosensor, the plasmonic interpretation verifying the resulting sensitivity improvement remains unclear. The aim of this study is to elucidate the effects of the grating's geometric parameters on the amplification of SPR responses and to understand the physical mechanisms associated with the enhancement. Our numerical results show that the proposed SPR substrate with a dielectric grating can provide a better sensitivity due to the combined effects of surface reaction area and field distribution at the binding region. An influence of adhesion layer on the sensor performance is also discussed. The obtained results will be promising in high-sensitivity plasmonic biosensing applications. PMID- 22781249 TI - Beam shaping for CARS measurements in turbulent environments. AB - This paper describes a new technique to mitigate the effect of beam steering on CARS measurements in turbulent, variable density environments. The new approach combines planar BOXCARS phase-matching with elliptical shaping of one of the beams to generate a signal robust to beam steering, while keeping the same spatial resolution. Numerical and experimental results are provided to demonstrate the effectiveness of this approach. One experiment investigates the effect of beam shaping in the presence of a controlled and well quantified displacement of the beams at the focal plane. Another experiment, more qualitative, proves the effectiveness of the technique in the presence of severe beam steering due to turbulence. PMID- 22781250 TI - Characterization technique of optical whispering gallery mode resonators in the microwave frequency domain for optoelectronic oscillators. AB - Optical Q factor measurements are performed on a whispering gallery mode (WGM) disk resonator using a microwave frequency domain approach instead of using an optical domain approach. An absence of hysteretic behavior and a better linearity are obtained when performing linewidth measurements by using a microwave modulation for scanning the resonances instead of the piezoelectric-based frequency tuning capability of the laser. The WGM resonator is then used to stabilize a microwave optoelectronic oscillator. The microwave output of this system generates a 12.48 GHz signal with -94 dBc/Hz phase noise at 10 kHz offset. PMID- 22781252 TI - Autonomous calibration method of the reference flat surface of an interferometer without using a standard flat surface. AB - An autonomous method for calibrating the reference flat surface of an interferometer is proposed with the uncertainty analysis. The method consists of three phases; the first step is multiple rotating shifts of a specimen, the second is a linear shift, and the last is multiple rotating shifts again. The profile of the reference flat surface is basically determined by the linear shift. The linear shift errors that occurred during the linear shift are identified by the rotating shifts. The rotating shift errors caused by the rotating shifts can be compensated and the residual uncertainty can be reduced in proportion to the square root of the number of rotating shifts per one revolution. Finally, the uncertainty analysis is carried out in detail. PMID- 22781251 TI - Metamaterial-based polarization control plate for producing incoherent laser irradiation. AB - We present a metamaterial-based random polarization control plate to produce incoherent laser irradiation by exploiting the ability of metamaterial in the local polarization manipulation of a beam upon transmission via tuning its local geometry. As a proof of principle, we exemplify this idea numerically in a simple optical system using a typical L-shaped plasmonic metamaterial with locally varying geometry, from which the desired polarization distribution can be obtained. The calculating results illustrate that this scheme can effectively suppress the speckle contrast and increase irradiation uniformity, which has potential to satisfy the increasing requirements for incoherent laser irradiation. PMID- 22781253 TI - Color transmission analysis of color computer-generated holography. AB - A color transmission approach between a computer display and a color computer generated holography (CCGH) colorimetric system is proposed based on color matching theory. Firstly, the conversion between color quantities of a computer display and a CCGH colorimetric system is discussed based on color matching theory. Secondly, the isochromatic transfer relationship of color quantity and amplitude of the object light field is proposed. Thirdly, the color object light field was encoded into a hologram, and then the hologram was reconstructed numerically. The simulation results demonstrate that our novel approach is feasible. PMID- 22781254 TI - Selective color imaging using weighted interleaved multiple annular linear diffractive axicons. AB - Annular linear diffractive axicons are optical devices providing chromatic imaging over an extended depth of focus when illuminated by a white light. To improve their low radiometric performance, multiple annular linear diffractive axicons (MALDAs) have been introduced. Their chromatic properties are well known and constrained by dispersion laws. A first attempt to freely combine colors or wavelength bands has been obtained with interleaved MALDAs (I_MALDAs). However, such optics do not provide a full decoupling between wavelength combination and brightness control required in the CIE color space to address any colors. We present here a new category of I_MALDA providing this capability when illuminated by a white source containing tristimulus (red/green/blue) values. We assess both theoretically and experimentally imaging qualities of such optics with respect to two different interleaving techniques and suggest some potential applications, in particular in the field of anticounterfeit and authentication techniques. PMID- 22781255 TI - Nonmechanical axial scanning laser Doppler velocimeter with directional discrimination. AB - An axial scanning laser Doppler velocimeter (LDV) with directional discrimination not requiring any moving mechanism in its probe is proposed. The proposed LDV utilizes frequency shift induced by acousto-optic modulators (AOMs) for discriminating the direction of velocity. The measurement position is axially scanned by changing the wavelength of the light input to the probe. The experimental result reveals that both the axial scan and the directional discrimination can be realized by using the proposed method without any moving element in the probe. PMID- 22781256 TI - Uncertainty in velocity measurement based on diode-laser absorption in nonuniform flows. AB - This work investigates the error caused by nonuniformities along the line-of sight in velocity measurement using tunable diode-laser absorption spectroscopy (TDLAS). Past work has demonstrated TDLAS as an attractive diagnostic technique for measuring velocity, which is inferred from the Doppler shift of two absorption features using two crossing laser beams. However, because TDLAS is line-of-sight in nature, the obtained velocity is a spatially averaged value along the probing laser beams. As a result, nonuniformities in the flow can cause uncertainty in the velocity measurement. Therefore, it is the goal of this work to quantify the uncertainty caused by various nonuniformities typically encountered in practice, including boundary layer effects, the divergence/convergence of the flow, and the methods used to fit the Doppler shift. Systematic analyses are performed to quantify the uncertainty under various conditions, and case studies are reported to illustrate the usefulness of such analysis in interpreting experimental data obtained from a scramjet facility. We expect this work to be valuable for the design and optimization of TDLAS-based velocimetry, and also for the quantitative interpretation of the measurements. PMID- 22781257 TI - Compensation of rotation effect in a combination of retarders. AB - In a cascaded system comprising a combination of oblique retarders, the effect of optical rotation is observed in addition to the overall retardation. This shows that the combined system does not behave as a pure oblique retarder. Analyzing such a general system using Pauli Spin matrices, it is shown that the effect of optical rotation may be completely annulled through the use of a suitably oriented retarder at the output of the cascaded system. The analysis assumes monochromaticity of the illuminating light beam. PMID- 22781258 TI - Designing a laser scanning picoprojector. Part 1: characteristics of the optical displaying system and color-management-related issues. AB - When designing a laser scanning picoprojector, one has to deal with important aspects that do not strictly involve design of hardware and software. We have identified two issues that play a decisive role in the final specifications of a laser scanning picoprojector: the characteristics of the optical displaying system and color management. Regarding the optical system, we have studied the diameter requirements of the laser beam emitted from a picoprojector from the point of view of image quality. Resolution is assessed by calculating the image modulation produced by a projected laser spot over a range of projection distances and image sizes. We also show that a suitable election of the RGB wavelengths increases the lumens-per-watt ratio and thereby improves efficiency of a laser-based picoprojector. PMID- 22781259 TI - Design of a multichannel, multiresolution smart imaging system. AB - This paper presents the design of a multichannel imaging system where the different optical channels have a different angular resolution and field-of-view. Such an imaging system is able to resolve fine details in a small region of interest through the channel that has the highest angular resolution (0.0096 degrees ) while controlling the surrounding region through the channel that has the widest field-of-view (2*40 degrees ). An interesting feature of such a multichannel, multiresolution imaging system is that various image processing algorithms can be applied at different segments of the image sensor. We have designed a three channel imaging system where each optical channel consists of four aspheric lens surfaces. These three imaging channels share a single image sensor with a resolution of 1440*960 and a 10 MUm pixel size. All imaging channels have diffraction-limited performance ensuring good overall image quality. PMID- 22781260 TI - Characterization of a low-speckle laser line generator. AB - The goal of our investigation is to design a low-speckle laser line generator based on partial spatially coherent laser light. Low speckle is achieved by exploiting a regime of strongly reduced spatial coherence of a broad-area vertical-cavity surface-emitting laser, which is used as the line generator's light source. A comparative experimental study of different optical configurations is conducted, leading to the design of an optimal optical system. The results of our study are also valid for other sources of partial spatially coherent emission. PMID- 22781261 TI - Three-dimensional protein shape rendering in magnetized solution with Lambert Beer law. AB - When monochromatic light passes through a homogeneous absorbing medium, the absorbance is proportional to the growth of concentration and thickness of the medium, which is the Lambert-Beer law. The shade selection of protein solution magnetized for a certain time from different angles makes different absorbance, which does not meet the Lambert-Beer law. Accordingly, we derive that the absorbance A is not only proportional to the concentration and thickness of the medium but also proportional to the light area S(S) of a certain direction. For the same protein solution, we can obtain the absorbance A of six directions and thus get six values for S(S) the relative ratio of which will inevitably reveal plentiful information of the protein shape. The conformation of the protein can be easily drawn out by software (MATLAB 7.0.1). We have drawn out the molecular shape of lysozyme and bovine serum albumin. In brief, we have developed the Lambert-Beer law A=K.C.b.S(s) and a new method of exploring protein spatial structure. PMID- 22781262 TI - Characterization of gloss properties of differently treated polymer coating surfaces by surface clarity measurement methodology. AB - With one measurement configuration, existing gloss measurement methodologies are generally restricted to specific gloss levels. A newly developed image-analytical gloss parameter called "clarity" provides the possibility to describe the perceptual result of a broad range of different gloss levels with one setup. In order to analyze and finally monitor the perceived gloss of products, a fast and flexible method also for the automated inspection is highly demanded. The clarity parameter is very fast to calculate and therefore usable for fast in-line surface inspection. Coated metal specimens were deformed by varying degree and polished afterwards in order to study the clarity parameter regarding the quantification of varying surface gloss types and levels. In order to analyze the correlation with the human gloss perception a study was carried out in which experts were asked to assess gloss properties of a series of surface samples under standardized conditions. The study confirmed clarity to exhibit considerably better correlation to the human perception than alternative gloss parameters. PMID- 22781263 TI - High sensitivity fiber optic angular displacement sensor and its application for detection of ultrasound. AB - In this paper, we report on the development of an intensity-modulated fiber-optic sensor for angular displacement measurement. This sensor was designed to present high sensitivity, linear response, and wide bandwidth and, furthermore, to be simple and low cost. The sensor comprises two optical fibers, a positive lens, a reflective surface, an optical source, and a photodetector. A mathematical model was developed to determine and simulate the static characteristic curve of the sensor and to compare different sensor configurations regarding the core radii of the optical fibers. The simulation results showed that the sensor configurations tested are highly sensitive to small angle variation (in the range of microradians) with nonlinearity less than or equal to 1%. The normalized sensitivity ranges from (0.25*V(max)) to (2.40*V(max)) mV/MUrad (where V(max) is the peak voltage of the static characteristic curve), and the linear range is from 194 to 1840 MUrad. The unnormalized sensitivity for a reflective surface with reflectivity of 100% was measured as 7.7 mV/MUrad. The simulations were compared with experimental results to validate the mathematical model and to define the most suitable configuration for ultrasonic detection. The sensor was tested on the characterization of a piezoelectric transducer and as part of a laser ultrasonics setup. The velocities of the longitudinal, shear, and surface waves were measured on aluminum samples as 6.43, 3.17, and 2.96 mm/MUs, respectively, with an error smaller than 1.3%. The sensor, an alternative to piezoelectric or interferometric detectors, proved to be suitable for detection of ultrasonic waves and to perform time-of-flight measurements and nondestructive inspection. PMID- 22781264 TI - Efficient and monolithic polarization conversion system based on a polarization grating. AB - We introduce a new polarization conversion system (PCS) based on a liquid-crystal polarization grating (PG) and louvered wave plate. A simple arrangement of these elements laminated between two microlens arrays results in a compact and monolithic element, with the ability to nearly completely convert unpolarized input into linearly polarized output across most of the visible bandwidth. In our first prototypes, this PG-PCS approach manifests nearly 90% conversion efficiency of unpolarized to polarized for +/-11 degrees input light divergence, leading to an energy efficient picoprojector that presents high efficacy (12 lm/W) with good color uniformity. PMID- 22781265 TI - Automated detection of exudates in colored retinal images for diagnosis of diabetic retinopathy. AB - Medical image analysis is a very popular research area these days in which digital images are analyzed for the diagnosis and screening of different medical problems. Diabetic retinopathy (DR) is an eye disease caused by the increase of insulin in blood and may cause blindness. An automated system for early detection of DR can save a patient's vision and can also help the ophthalmologists in screening of DR. The background or nonproliferative DR contains four types of lesions, i.e., microaneurysms, hemorrhages, hard exudates, and soft exudates. This paper presents a method for detection and classification of exudates in colored retinal images. We present a novel technique that uses filter banks to extract the candidate regions for possible exudates. It eliminates the spurious exudate regions by removing the optic disc region. Then it applies a Bayesian classifier as a combination of Gaussian functions to detect exudate and nonexudate regions. The proposed system is evaluated and tested on publicly available retinal image databases using performance parameters such as sensitivity, specificity, and accuracy. We further compare our system with already proposed and published methods to show the validity of the proposed system. PMID- 22781266 TI - Side-hole two-core microstructured optical fiber for hydrostatic pressure sensing. AB - A novel side-hole two-core microstructured optical fiber (STMOF) is proposed for hydrostatic pressure sensing. The two solid fiber cores are surrounded by a few small air holes and two large air holes, and are separated by one small air hole in the center of the cross section of the STMOF. The two large air holes that we called side holes essentially provide a built-in transducing mechanism to enhance the pressure-induced index change, which ensures the high sensitivity of the hydrostatic pressure sensor based on the STMOF. Mode coupling between the two fiber cores of the STMOF has been investigated, which provides a pressure dependent transmission spectrum by injecting a broadband light into one fiber core of the STMOF on one side and detecting output spectrum on another fiber core on the other side. Our simulations show that there is a one-to-one correspondence between the hydrostatic pressure applied on the STMOF and the peak wavelength shift of the transmission spectrum. A hydrostatic pressure sensor based on an 8 cm STMOF has a sensitivity of 0.111 nm/Mpa for the measurement range from 0 Mpa to 200 Mpa. The performances of hydrostatic pressure sensors based on STMOFs with different structure parameters are presented. PMID- 22781267 TI - Influence of thickness error on the operation of adjustable magneto-optical isolators. AB - We have performed a theoretical study on the case of transmission-type one dimensional magnetophotonic crystals (MPCs) to establish a practical magneto optical isolator (MOI) that operates properly even in the presence of construction errors. We have introduced a very thin MPC structure with high transmittance and a large Faraday rotation, with the capability of adjusting to a perfect MOI. A minor thickness error for the individual layers of this MOI may take it from being a perfect MOI; however, its adjustability can provide a stable operation against fabrication errors. PMID- 22781268 TI - Method for improving terahertz band absorption spectrum measurement accuracy using noncontact sample thickness measurement. AB - The terahertz absorption spectrum has a complex nonlinear relationship with sample thickness, which is normally measured mechanically with limited accuracy. As a result, the terahertz absorption spectrum is usually determined incorrectly. In this paper, an iterative algorithm is proposed to accurately determine sample thickness. This algorithm is independent of the initial value used and results in convergent calculations. Precision in sample thickness can be improved up to 0.1 MUm. A more precise absorption spectrum can then be extracted. By comparing the proposed method with the traditional method based on mechanical thickness measurements, quantitative analysis experiments on a three-component amino acid mixture shows that the global error decreased from 0.0338 to 0.0301. PMID- 22781269 TI - Thermal-light-based ranging using second-order coherence. AB - A novel thermal-light-based ranging scheme utilizing second-order coherence in the time domain is proposed and studied. Such a scheme allows ultrahigh accuracy to be achieved for absolute range measurement. Besides, the scheme has the advantages of high immunity to noise and no measuring dead zone. A proof-of principle experiment has been done, and the result shows a +/-10 cm accuracy at a distance of 1 km, which is currently limited by our detectors. The accuracy can be greatly improved to the nanometer scale by using state-of-the-art detectors with an appropriate data processing algorithm. PMID- 22781270 TI - Single-shot parallel four-step phase shifting using on-axis Fizeau interferometry. AB - The purposes of the paper are threefold: (1) to show the possibility to perform parallel phase-shifting Fizeau interferometry by using a quarter waveplate with high flatness as a reference, (2) to present a comparative study between the phase-shifting algorithm and the off-axis geometry in surface microtopography measurement, and (3) to show the advantages of using the proposed common path Fizeau interferometry over the quasi-common path Michelson interferometry in terms of accuracy in measurement. The compelling advantage of the proposed parallel phase-shifting Fizeau interferometric technique is the long-term stability that leads to measuring objects with a high degree of accuracy. PMID- 22781271 TI - Influence of depth of intermediate layer on optical power distribution in W-type optical fibers. AB - For different depth and width of the intermediate layer, a power flow equation is used to calculate spatial transients and steady state of power distribution in W type optical fibers (doubly clad fibers with three layers). A numerical solution has been obtained by the explicit finite difference method. Results show how the power distribution in W-type optical fibers varies with the depth of the intermediate layer for different values of intermediate layer width and coupling strength. We have found that with increasing depth of the intermediate layer, the fiber length at which the steady-state distribution is achieved increases. Such characterization of these fibers is consistent with their manifested effectiveness in reducing modal dispersion and improving bandwidth. PMID- 22781272 TI - Polarization-independent wideband mixed metal dielectric reflective gratings. AB - A polarization-independent wideband mixed metal dielectric grating with high efficiency of the -1st order is analyzed and designed in Littrow mounting. The mixed metal dielectric grating consists of a rectangular-groove transmission dielectric grating on the top layer and a highly reflective mirror composed of a connecting layer and a metal film. Simplified modal analysis is carried out, and it shows that when the phase difference accumulated by the two propagating modes is odd multiples of pi/2, the diffraction efficiency of the -1st order will be high. Selecting grating depth and duty cycle for satisfying the phase difference condition for both TE (electric field parallel to grooves) and TM (magnetic field parallel to grooves) polarizations, a polarization-independent high-efficiency grating can be designed. Using rigorous coupled-wave analysis and a simulated annealing algorithm, geometric parameters of the reflective grating are exactly obtained. The optimized grating for operation around a wavelength of 800 nm exhibits diffraction efficiencies higher than 90% for both TE and TM polarizations over a 120 nm wavelength bandwidth. The simplified modal analysis can be applied in other types of reflective gratings if the top layer is a dielectric transmission grating. PMID- 22781273 TI - High accuracy alignment facility for the receiver and transmitter of the BepiColombo Laser Altimeter. AB - The accurate co-alignment of the transmitter to the receiver of the BepiColombo Laser Altimeter is a challenging task for which an original alignment concept had to be developed. We present here the design, construction and testing of a large collimator facility built to fulfill the tight alignment requirements. We describe in detail the solution found to attenuate the high energy of the instrument laser transmitter by an original beam splitting pentaprism group. We list the different steps of the calibration of the alignment facility and estimate the errors made at each of these steps. We finally prove that the current facility is ready for the alignment of the flight instrument. Its angular accuracy is 23 MUrad. PMID- 22781274 TI - Overview of anisotropic filtering methods based on partial differential equations for electronic speckle pattern interferometry. AB - In this paper, we first present the general description for partial differential equations (PDEs) based image processing methods, including the basic idea, the main advantages and disadvantages, a few representative PDE models, and the derivation of PDE models. Then we review our contributions on PDE-based anisotropic filtering methods for electronic speckle pattern interferometry, including the second-order, fourth-order, and coupled nonoriented PDE filtering models and the second-order and coupled nonlinear oriented PDE filtering models. We have summarized the features of each model. PMID- 22781275 TI - Nanoscale alloying effect of gold-platinum nanoparticles as cathode catalysts on the performance of a rechargeable lithium-oxygen battery. AB - The understanding of nanoscale alloying or the phase segregation effect of alloy nanoparticles on the catalytic properties is important for a rational design of the desired catalysts for a specific reaction. This paper describes findings of an investigation into this type of structural effect for carbon-supported bimetallic gold-platinum nanoparticles as cathode catalysts in a rechargeable lithium-oxygen battery. The nanoscale structural characteristics in terms of size, alloying and phase segregation were shown to affect the catalytic properties of the catalysts in the Li-O(2) battery. In addition to the composition effect, the catalysts with a fully alloyed phase structure were found to exhibit a smaller discharge-charge voltage difference and a higher discharge capacity than those with a partial phase segregation structure. This finding is significant for the design of alloy nanoparticles as air cathode catalysts in rechargeable lithium-air batteries, demonstrating the importance of the control of the nanoscale composition and phase properties. PMID- 22781277 TI - Assessment of polymorphic genetic markers for multi-locus typing of Cryptosporidium parvum and Cryptosporidium hominis. AB - The use of high resolution molecular tools to study Cryptosporidium parvum and Cryptosporidium hominis intra-species variation is becoming common practice, but there is currently no consensus in the methods used. The most commonly applied tool is partial gp60 gene sequence analysis. However, multi-locus schemes are acknowledged to improve resolution over analysis of a single locus, which neglects potential re-assortment of genes during the sexual phase of the Cryptosporidium life-cycle. Multi-locus markers have been investigated in isolates from a variety of sampling frames, in varying combinations and using different assays and methods of analysis. To identify the most informative markers as candidates for the development of a standardised multi-locus fragment size-based typing (MLFT) scheme to integrate with epidemiological analyses, we examined the published literature. A total of 31 MLFT studies were found, employing 55 markers of which 45 were applied to both C. parvum and C. hominis. Of the studies, 11 had sufficient raw data, from three or more markers, and a sampling frame containing at least 50 samples, for meaningful in-depth analysis using assessment criteria based on the sampling frame, study size, number of markers investigated in each study, marker characteristics (>2 nucleotide repeats) and the combinations of markers generating all possible multi-locus genotypes. Markers investigated differed between C. hominis and C. parvum. When each scheme was analysed for the fewest markers required to identify 95% of all MLFTs, some redundancy was identified in all schemes; an average redundancy of 40% for C. hominis and 27% for C. parvum. Ranking markers, based on the most productive combinations, identified two different sets of potentially most informative candidate markers, one for each species. These will be subjected to technical evaluation including typability (percentage of samples generating a complete multi-locus type) and discriminatory power by direct fragment size analysis and analysed for correlation with epidemiological data in suitable sampling frames. The establishment of a group of users and agreed subtyping scheme for improved epidemiological and public health investigations of C. parvum and C. hominis will facilitate further developments and consideration of technological advances in a harmonised manner. PMID- 22781278 TI - A high-fat diet associated with acute schistosomiasis mansoni causes disorganization in splenic architecture in mice. AB - To date, the effect of the changes promoted by hypercholesterolemia and experimental schistosomiasis infection on splenic architecture has remained elusive. In this paper, we compared spleen from control and infected mice fed either high-fat (29% lipids) or standard diet (12% lipids), assessing spleen volume by liquid displacement and splenic disorganization by histopathology, morphometry and stereology. Infected mice showed higher spleen volume than in corresponding uninfected mice (P<0.05). The white pulp compartment was reduced, red pulp and germinal center were enhanced (P<0.01). Microscopic examination showed cellular infiltrates characterized by polymorfonuclear cells, with intensive lymphocytic mitosis and Mott cells. Hemosiderin deposits tended to be in less extent in infected mice compared with uninfected controls. The red pulp compartment showed a significantly (P<0.05) increased average number of megakaryocytes compared with uninfected mice, which may be associated with hematopoietic reconstitution. High-fat fed mice showed larger white pulp than controls (P<0.05). Standard fed mice showed exudative-productive granuloma distributed only sparsely in the red pulp, whereas a tissue reaction characterized by a cell infiltration in high-fat fed mice was found. The results of the present study suggest that there is a significant relationship between high-fat diet intake and splenic disorganization such as a decrease in the numerical density of white pulp and, red pulp and germinal center hyperplasia. Such structural disorganization due to co-morbidites (schistosomiasis and dyslipidemia) may affect the microenvironments of the spleen that are necessary for the generation of immune responses to antigens. PMID- 22781276 TI - Nutritional regulation of genome-wide association obesity genes in a tissue dependent manner. AB - BACKGROUND: Genome-wide association studies (GWAS) have recently identified several new genetic variants associated with obesity. The majority of the variants are within introns or between genes, suggesting they affect gene expression, although it is not clear which of the nearby genes they affect. Understanding the regulation of these genes will be key to determining the role of these variants in the development of obesity and will provide support for a role of these genes in the development of obesity. METHODS: We examined the expression of 19 GWAS obesity genes in the brain and specifically the hypothalamus, adipose tissue and liver of mice by real-time quantitative PCR. To determine whether these genes are nutritionally regulated, as may be expected for genes affecting obesity, we compared tissues from fasting and non-fasting animals and tissues from mice consuming a high fat high sucrose diet in comparison to standard rodent chow. RESULTS: We found complex, tissue-dependent patterns of nutritional regulation of most of these genes. For example, Bat2 expression was increased ~10-fold in the brain of fed mice but was lower or unchanged in the hypothalamus and adipose tissue. Kctd15 expression was upregulated in the hypothalamus, brain and adipose tissue of fed mice and downregulated by high fat feeding in liver, adipose tissue and the hypothalamus but not the remainder of the brain. Sh2b1 expression in the brain and Faim2 expression in adipose tissue were specifically increased >20-fold in fed mice. Tmem18 expression in adipose tissue but not the brain was reduced 80% by high fat feeding. Few changes in the expression of these genes were observed in liver. CONCLUSIONS: These data show nutritional regulation of nearly all these GWAS obesity genes, particularly in the brain and adipose tissue, and provide support for their role in the development of obesity. The complex patterns of nutritional and tissue-dependent regulation also highlight the difficulty that may be encountered in determining how the GWAS genetic variants affect gene expression and consequent obesity risk in humans where access to tissues is constrained. PMID- 22781279 TI - Microbispora thailandensis sp. nov., an actinomycete isolated from cave soil. AB - The taxonomic position of actinomycete strain NN276(T), isolated from cave soil, was studied using the polyphasic taxonomic approach. A phylogenetic tree based on 16S ribosomal RNA (rRNA) gene sequences showed that the isolate formed a distinct evolutionary linage with the genus Microbispora, with M. mesophila JCM 3151(T) as its closest phylogenetic neighbor (97.9% similarity). The organism contained meso diaminopimelic acid and the N-acetyl type of peptidoglycan. Madurose was detected in the whole-cell hydrolasate. The predominant menaquinones were MK-9(H(4)), MK 9(H(2)) and MK-9. Mycolic acids were not detected. Major phospholipids were diphosphatidylglycerol, hydroxy-phosphatidylethanolamine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major cellular fatty acid was iso-C(16: 0) and G+C content 70 mol%. DNA-DNA hybridization demonstrated that the isolate was distinct from M. mesophila JCM 3151(T). On the basis of phenotypic and genotypic data, it is proposed that strain NN276(T) represents a novel species of the genus Microbispora, hence the name Microbispora thailandensis sp. nov. The type strain is strain NN276(T) (=BCC 41490(T)=NRRL B-24806(T)=NBRC 107569(T)). PMID- 22781280 TI - Antibacterial activity of amphiphilic tobramycin. AB - Amphiphilic aminoglycoside antimicrobials are an emerging class of new antibacterial agents with novel modes of action. Previous studies have shown that amphiphilic neomycin-B and kanamycin-A analogs restore potent antibacterial activity against Gram-positive neomycin-B- and kanamycin-A-resistant organisms. In this paper, we investigated the antibacterial properties of a series of amphiphilic tobramycin analogs. We prepared tobramycin-lipid conjugates, as well as tobramycin-peptide triazole conjugates, and studied their antibacterial activities against a panel of Gram-positive and Gram-negative bacterial strains, including isolates obtained from Canadian hospitals. Our results demonstrate that the antibacterial activity of amphiphilic tobramycin is greatly affected by the length and nature of the hydrophobic lipid tail, whereas the nature of the polycationic headgroup or the number of cationic charges appear to be less important. Replacement of the hydrophobic tail by a fluorinated lipid confers good activity against two Pseudomonas strains and reduces hemolytic activity. However, susceptibility studies in the presence of bovine serum albumin indicate that all amphiphilic tobramycin analogs are strongly protein-bound, leading to a typical four- to eight-fold increase in MIC. PMID- 22781281 TI - Two streptothricins with a cis-streptolidine lactam moiety from Streptomyces sp. I08A 1776. AB - Two unique cis-fused streptothricins (1 and 2) were isolated from the culture broth of Streptomyces sp. I08A 1776. Their structures were determined by MS, CD, and 1D and 2D NMR spectroscopic data analysis. Compound 2 showed weak antibacterial activities against Bacillus subtilis and Enterococcus faecalis with MIC values of 32 and 64 MUg ml(-1), respectively. PMID- 22781282 TI - Urease expression in a Thermoanaerobacterium saccharolyticum ethanologen allows high titer ethanol production. AB - Genes encoding the enzyme urease were integrated in a Thermoanaerobacterium saccharolyticum ethanologen. The engineered strain hydrolyzed urea, as evidenced by increased cellular growth and elevated final pH in urea minimal medium and urease activity in cell free extracts. Interestingly, replacement of ammonium salts with urea resulted in production of 54 g/L ethanol, one of the highest titers reported for Thermoanaerobacterium. The observed increase in ethanol titer may result from reduced pH, salt, and osmolality stresses during fermentation. Urea utilization is attractive for industrial scale fermentation, where pH control is technically challenging and increased ethanol titer is desirable. PMID- 22781283 TI - Metabolic engineering of Escherichia coli BL21 for biosynthesis of heparosan, a bioengineered heparin precursor. AB - As a precursor of bioengineered heparin, heparosan is currently produced from Escherichia coli K5, which is pathogenic bacteria potentially causing urinary tract infection. Thus, it would be advantageous to develop an alternative source of heparosan from a non-pathogeneic strain. In this work we reported the biosynthesis of heparosan via the metabolic engineering of non-pathogenic E. coli BL21 as a production host. Four genes, KfiA, KfiB, KfiC and KfiD, encoding enzymes for the biosynthesis of heparosan in E. coli K5, were cloned into inducible plasmids pETDuet-1 and pRSFDuet-1 and further transformed into E. coli BL21, yielding six recombinant strains as follows: sA, sC, sAC, sABC, sACD and sABCD. The single expression of KfiA (sA) or KfiC (sC) in E. coli BL21 did not produce heparosan, while the co-expression of KfiA and KfiC (sAC) could produce 63 mg/L heparosan in shake flask. The strain sABC and sACD could produce 100 and 120 mg/L heparosan, respectively, indicating that the expression of KfiB or KfiD was beneficial for heparosan production. The strain sABCD could produce 334 mg/L heparosan in shake flask and 652 mg/L heparosan in 3-L batch bioreactor. The heparosan yield was further increased to 1.88 g/L in a dissolved oxygen-stat fed batch culture in 3-L bioreactor. As revealed by the nuclear magnetic resonance analysis, the chemical structure of heparosan from recombinant E. coli BL21 and E. coli K5 was identical. The weight average molecular weight of heparosan from E. coli K5, sAC, sABC, sACD, and sABCD was 51.67, 39.63, 91.47, 64.51, and 118.30 kDa, respectively. This work provides a viable process for the production of heparosan as a precursor of bioengineered heparin from a safer bacteria strain. PMID- 22781284 TI - [New path on Helicobacter pylori infection treatment]. PMID- 22781285 TI - [Strategy of adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer]. PMID- 22781286 TI - [Endocrine therapy combined with mTOR inhibitor for hormone receptor-positive breast cancer]. PMID- 22781287 TI - [Genotyping of mutations contributing to antibiotic resistance and Helicobacter pylori eradication therapy]. PMID- 22781288 TI - [The strategic planning of oral Helicobacter pylori infection treatment: an important issue facing us today]. PMID- 22781289 TI - [Application of furazolidone-based regimens for Helicobacter pylori eradication]. PMID- 22781290 TI - [Investigations on a new combined therapy of traditional Chinese and Western medicine in the treatment of Helicobacter pylori infection]. PMID- 22781291 TI - [Individualized treatment in the eradication therapy for Helicobacter pylori]. PMID- 22781292 TI - [Combination of recombinant human endostatin and neoadjuvant chemotherapy for breast cancer]. AB - OBJECTIVE: Recombinant human endostatin (rh-Endostatin), a protein modified by an additional nine-amino acid sequence to the N-terminal of endostatin, is a novel antiangiogenesis drug developed in China. The preclinical data suggested that it can inhibit proliferation and migration not only in endothelial cells, but also in some types of tumor cells. Theoretically, antiangiogenesis drugs should also be effective in the therapy of other solid tumors, including breast cancer. Here a prospective, randomized, controlled, phase II trial of combining rh-Endostatin and neoadjuvant chemotherapy was performed to evaluate its efficacy and safety profiles in patients with breast cancer. METHODS: A total of 68 patients with pathologically confirmed breast cancer were randomly assigned to receive the neoadjuvant DE regimen (docetaxel: 75 mg/m(2), d1, epirubicin: 75 mg/m(2), d1) every 3 weeks with or without rh-Endostatin (7.5 mg/m(2), d1-d14). Surgical resection was performed after 3 cycles of neoadjuvant treatment. The primary end points were objective response rate (ORR) and pathological complete response rate (PCRR) while the secondary end-points quality of life (QOL) and toxicity. RESULTS: Among all of them, 64 were assessable for efficacy and 68 for toxicity. The ORRs were 90.9% (30/33) and 67.7% (21/31) in the combination and control groups respectively (P = 0.021). The stratification analysis showed that rh Endostatin was more effective in the treatment of pre-menopausal and Eastern Cooperative Oncology Group (ECOG) = 0 patients (P < 0.05). The PCRRs were 15.2% (5/33) and 6.5% (2/31) in the combination and control groups respectively (P = 0.428). No significant difference was identified in QOL score and side effects (P > 0.05). CONCLUSIONS: Compared with DE regimen alone, the combination of rh Endostatin with DE chemotherapy may achieve a higher ORR with no increased toxicity in breast cancer patients. Thus it can be utilized safely and effectively in the neoadjuvant treatment of breast cancer. PMID- 22781293 TI - [Morphology-based criteria for ultrasonic assessment of axillary lymph node status in primary breast cancer]. AB - OBJECTIVE: To evaluate the morphology-based criteria for the ultrasonic assessment of axillary lymph node in primary breast cancer. METHODS: A total of 2256 T0-2N0 patients underwent axillary ultrasound preoperatively. Lymph nodes were classified as normal if no node was found or cortex thickness was even and < 3 mm; abnormal, (1) if cortex thickness was even but >= 3 mm or (2) focally thickened cortex >= 3 mm or (3) fatty hilum was absent. The patients in the abnormal group underwent ultrasound guided fine-needle aspiration (US-FNA). Except for positive lymph nodes, all the others underwent sentinel lymph node biopsy (SLNB). RESULTS: In this series, 692 (30.7%) were pathologically confirmed positive LNs. Among them, 214 (9.5%) were identified by US-FNA. And 361 were abnormal according to the above mentioned criteria. The proportions were 11.6%, 54.8% and 33.5% in Group 1-3 respectively. The sensitivity, specificity, positive and negative predictive values of these criteria alone were 35.8%, 92.8%, 68.7% and 76.6% respectively. CONCLUSION: The present morphology-based criteria for the ultrasonic assessment of lymph node status is both effective and practical in primary breast cancer. PMID- 22781294 TI - [Comparative analysis on risk factors of axillary lymph node metastasis in Uygur and Han patients with breast cancer]. AB - OBJECTIVE: To comparatively explore the risk factors of axillary lymph node metastasis (ALNM) in Uygur and Han patients with breast cancer. METHODS: A total of 243 female Han patients and 66 Uygur ones with T(1) stage breast cancer were retrospectively studied by single and multi-factorial Logistic regression analysis. RESULTS: The rates of ALNM were 43.94% and 30.86% in Uygur and Han patients respectively. There was statistic difference between them. Statistic differences existed between these two nationals in gravidity and parity. Multi Factorial Logistic regression analysis showed that age, gravidity and quadrant of tumor localized were the risk factors of ALNM while estrogen receptor (ER)(+) was the protective factor. CONCLUSIONS: The rate of ALNM in Uygur patients with T(1) stage breast cancer is higher than that in Han counterparts. More gravidity is an influencing factor. Younger age, more gravidity and location of tumor are the high risk factors for ALNM while ER(+) is the protective factor. PMID- 22781295 TI - [Jinghuaweikang capsules combined with triple therapy in the treatment of Helicobacter pylori associated gastritis and duodenal ulcer and analysis of antibiotic resistance: a multicenter, randomized, controlled, clinical study]. AB - OBJECTIVE: To explore the efficacy of Jinghuaweikang capsules plus triple therapy (LACJ) in treatment of Helicobacter pylori (H. pylori) associated gastritis or duodenal ulcer, compare it with bismuth-containing quadruple therapy (LACB) and standard triple therapy (LAC) and analyze the antibiotic sensitivity of gastric mucosal H. pylori strains from the failed patients. METHODS: A total of 565 patients with H. pylori infection were recruited from 11 hospitals from January 2010 to June 2011. There were 336 males and 229 females. They underwent gastroendoscopy examination due to upper gastrointestinal symptoms and had never received H. pylori eradication therapies. Duodenal ulcer patients were divided randomly into LACJ therapy group, LACB therapy group and LAC therapy group while gastritis patients LACJ therapy group and LACB therapy group. Group LAC received lansoprazole 30 mg + amoxicillin 1000 mg + clarithromycin 500 mg, twice a day, for 7 d (d1-7). Group LACJ: LAC therapy plus Jinghuaweikang, 3 capsules, twice a day, for 7 d (d1-7) then Jinghuaweikang, 3 capsules, twice a day, for 14 d (d8 21). Group LACB: LAC plus bismuth potassium citrate 220 mg, twice a day, for 7 d (d1-7) and then bismuth potassium citrate 220 mg, twice a day, for 14 d (d8-21). All duodenal ulcer patients received lansoprazole (30 mg, once a day) for 14 days after the first 7-day of treatment (d 8-21). At least 28 days after the end of treatment, all patients underwent (13)C urea breath test. Gastric mucosa was collected under endoscopy from the failed patients. The detection technique of gene chip was employed to detect antibiotics resistant gene from mucosa. RESULTS: The eradication rates of duodenal ulcer patients in groups LACJ, LACB and LAC were as follows: per-protocol (PP), 80.2% (77/96), 89.9% (89/99) and 72.2% (70/97) (P = 0.007), intention-to-treat (ITT), 78.6% (77/98), 88.1% (89/101) and 70.0% (70/100) (P = 0.007). No statistical differences existed between groups LACJ and LACB or LAC (all P > 0.05). But there were statistical differences between groups LACB and LAC (both P = 0.002). The eradication rates of PP and ITT of chronic gastritis patients in groups LACJ and LACB were as follows: 75.8% (97/128), 74.6% (97/130) vs 83.8% (109/130), 80.1% (109/136) (both P > 0.05). The symptomatic improvements of abdominal pain, burning and acid reflux of duodenal ulcer patients in group LACJ were higher than those in groups LACB and LAC. There were statistical differences between groups LACJ and LAC (all P < 0.05). The symptomatic improvements of bloating and belching for chronic gastritis patients in group LACJ were higher than those of group LACB. But no significant difference existed between two groups (all P > 0.05). Sixty samples of gastric mucosa were collected from the failed patients. The detection rates of antibiotic-resistant gene to clarithromycin and amoxicillin were 60.0% (36/36) and 18.3% (11/60) respectively. CONCLUSIONS: The efficacy of LACJ for the treatment of H. pylori infection patients is similar to LACB and superior to LAC. And the symptomatic improvement of patients is better than the other two regimens. The main cause of treatment failure is antibiotic resistance of H. pylori strains. PMID- 22781296 TI - [Correlation of large artery stiffness and coronary flow velocity reserve]. AB - OBJECTIVE: Coronary flow velocity reserve (CFVR) is an important indicator of coronary endothelial functions and microcirculation. Pulse wave velocity (PWV) reflects the degree of aortic sclerosis and it is an independent predictor of cardiovascular events. The present study was designed to evaluate the correlation of large artery stiffness and CFVR. METHODS: A total of 101 consecutive subjects were enrolled to measure the brachial-ankle pulse wave velocity (baPWV). According to the presence or absence of higher baPWV (> 1400 cm/s), they were divided into 2 groups. Transthoracic echocardiography was employed to measure coronary flow velocity in coronary left anterior descending (LAD). Then after an intravenous infusion of adenosine triphosphate, the velocity of blood flow was measured when the vessel was in maximal dilation. The ratio of flow velocity of those in maximal dilation to those at rest was CFVR. RESULTS: The subjects with a higher baPWV (> 1400 cm/s) were markedly elder and had higher risks of hypertension and diabetes. Thus age, hypertension and diabetes contributed to arteriosclerosis. More importantly, the subjects with a higher baPWV (> 1400 cm/s) had a much lower level of CFVR (2.66 +/- 0.74 vs 2.95 +/- 0.76; P < 0.01) than those with a lower baPWV (< 1400 cm/s). Furthermore correlation analysis showed that CFVR and baPWV levels were significantly negatively correlated (r = 0.35, P < 0.01). CONCLUSIONS: A negative correlation exists between artery stiffness and coronary flow velocity reserve. The increased vascular stiffness may impair coronary endothelial function, cause the dysfunction of coronary microcirculation and raise the risks of cardiovascular events. PMID- 22781297 TI - [Clinical efficacies and safety of HAG regimen for patients with high-risk myelodysplastic syndromes: a multicentre study]. AB - OBJECTIVE: To evaluate the efficacies and toxicity of HAG (HHT + Ara-C + G-CSF) regimen in patients with high-risk myelodysplastic syndromes (MDS). METHODS: A total of 97 patients with high-risk MDS received HAG regimen as the induction therapy. RESULTS: The complete remission (CR) rate of all the patients was 52.3% (45/86). The overall response (OR) rate was 66.3% (57/86). The early mortality rate was 9.3% (9/97). There was no significant difference in CR rate and OR rate between the patients aged >= 60 and those < 60. The OR rate was 29/34, 9/12 and 6/13 in patients with favorable karyotype, intermediate karyotype and unfavorable karyotype respectively. The OR rate was higher in patients with favorable karyotype than those with unfavorable karyotype (P = 0.038). The major adverse effect was infection. CONCLUSION: HAG regimen provides higher CR rate and OR rate for patients with high-risk MDS. PMID- 22781298 TI - [Differential expression profile of microRNA between hyperplastic scar and normal skin]. AB - OBJECTIVE: To explore the miRNA differential expression profiles of hyperplastic scar and normal skin so as to further elucidate the pathogenesis of hyperplastic scar and search for new therapeutic targets. METHODS: The total RNA was extracted from 5 human hyperplastic scar and normal skin tissues by Trizol. The specimens were collected from the First Affiliated Hospital of Nanchang University from November 2010 to May 2011, and purified by mirVana(TM) miRNA Isolation Kit and then labeled and hybridized by miRNA Complete Labeling and Hyb Kit. The images of hybridization were analyzed by the Feature Extraction (v10.7) software and the microarray results confirmed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In hyperplastic scar, 92 miRNA genes were up-regulated and 13 down-regulated. The most significantly up-regulated miRNAs were hsa-miR-564 and hsa-miR-936, etc. while hsa-miR-451, hsa-miR-223, hsa miR-363 and hsa-miR-29b-1* became significantly down-regulated. The findings of RT-PCR on hsa-miR-21 and hsa-miR-451 of regulation were in a high concordance with the microarray results. CONCLUSION: Distinct differences of miRNA expression between human hyperplastic scar and normal skin, it may be closely correlated with the formation, development and evolution of hyperplastic scar. PMID- 22781299 TI - [1alpha, 25(OH)(2) D(3) protects pancreatic beta-cell line from cytokine-induced apoptosis and impaired insulin secretion]. AB - OBJECTIVE: To explore the protective effects and potential mechanisms of 1alpha, 25(OH)(2) D(3) (VitD(3)) on pancreatic beta-cells. METHODS: The apoptosis of NIT 1 cells was induced by interleukin-1beta (IL-1beta) and interferon-gamma (IFN gamma) in vitro. Then the apoptotic rate of NIT-1 cells was determined by Hoechest33342 staining and Annexin V-FITC/PI flow cytometry. The insulin secretion level of NIT-1 cells was measured by ELISA. The NIT-1 cells were treated with VitD(3) at the final concentrations of 10(-8) mol/L or underwent transient transfection with vitamin D receptor (VDR)-SiRNA. RESULTS: After the treatment of VitD(3), the apoptotic rate of NIT-1 cells decreased to 39.7%. There were significant differences in apoptotic rate between the VitD(3) treatment and IL-1beta/IFN-gamma groups (68.4%) (P < 0.01). Similarly impaired glucose stimulated insulin secretion (GSIS) of NIT-1 cells recovered ((7.34 +/- 0.21) ng/ml) after the treatment of VitD(3) as compared with the IL-1beta/IFN-gamma group ((4.88 +/- 0.32) ng/ml, P < 0.01). Moreover, most of the protective effects of VitD(3) on pancreatic beta-cells could be blocked by the transfection of VDR SiRNA. CONCLUSION: VitD(3) may protect pancreatic beta-cells from cytokine induced apoptosis and impaired insulin secretion through its conjugation with VDR. PMID- 22781300 TI - [Preliminary study of biological mechanism and apoptotic effect induced by YM155 in SUDHL-4 cell line]. AB - OBJECTIVE: To explore the apoptotic effect of follicular lymphoma and related mechanism induced by YM155 in vitro and provide laboratory rationales for the clinical treatment of follicular of lymphoma with YM155 in the future. METHODS: SUDHL-4 cells were cultured to logarithmic phase and transferred to 96-well plates. There were a series of YM155 concentration gradients: 100, 10, 1, 0.1 and 0 ng/ml and cultured for 24, 48 and 72 h. After the addition of CCK-8 reagent for 2 h at each time point, optical density values were obtained from the cell growth inhibition curves depending on time and drug concentration and the half growth inhibition concentration (IC(50)) values calculated. SUDHL-4 cells were co cultured with YM155 (1 ng/ml) for 0, 24, 48 and 72 h respectively. Then flow cytometry (FCM) was used to detect apoptosis. SUDHL-4 cell line was treated with YM155 for 24 and 48 h to extract the total RNA. The mRNA expressions of bcl-2, bcl-xl, bid, bax and survivin gene at the time point of 48 h and the survivin mRNA expression at 24 h were detected by reverse transcription-PCR (RT-PCR). The protein expressions of survivin, caspase-9, cleaved caspase-9, caspase-3 and cleaved caspase-3 were detected at each time point with Western blot respectively. RESULTS: SUDHL-4 cell line showed significant growth inhibition effect depending on time and dose. And the 24, 48, 72 h IC(50) was 6.1, 2.7 and 1.2 ng/ml respectively. SUDHL-4 cells stained AnnexinV-FITC and PI examined by FCM demonstrated that the proportion of AnnexinV-FITC positive cells gradually increased with time (17.3% +/- 2.1%, 35.7% +/- 3.3%, 54.6% +/- 4.3% vs 2.1% +/- 0.3%, all P < 0.05). And the results of real-time fluorescent PCR proved that YM155 decreased the expression of survivin gene obviously (24 h: 0.72 +/- 0.02, 48 h: 0.56 +/- 0.01 vs 1.00, both P < 0.05) but had little effects on the gene expressions of bax, bid, bcl-2 and bcl-xl. The Western blot results further confirmed that the protein expressions of survivin and caspase-3 decreased with time while caspase-9 and cleaved caspase-9 showed no obvious changes. But cleaved caspase-3 increased significantly. CONCLUSIONS: YM155 displays significant apoptotic effects in SUDHL-4 cell lines. The mechanism may be the direct activation of caspase-3 through the down-regulation of survivin. And the apoptotic pathway is probably not regulated by bcl-2 family. PMID- 22781301 TI - [Experimental study of rat mesenchymal stem cells transfected with Sonic Hedgehog gene]. AB - OBJECTIVE: To evaluate the feasibility of genetic modification of mesenchymal stem cells (MSC) with Sonic Hedgehog (Shh) gene. METHODS: The pcDNA3.1-Shh eukaryotic expression plasmid was constructed and its correctness evaluated by the restriction enzyme analysis and sequencing. MSC were isolated from Wistar rats by density gradient centrifugation and purified, transfected with pcDNA3.1 Shh, blank plasmid pcDNA3.1(-) or pmaxGFP respectively by Nucleofector(TM). The protein expression of Shh in MSC was detected by Western blot after 48 hours. RESULTS: Correct construction of pcDNA3.1-Shh was identified by the methods of restriction enzyme analysis and nucleotide sequence determination. The expression of green fluorescent protein (GFP) could be observed by fluorescence microscopy after 48 hours. The expression of Shh gene was detected by Western blot. But the MSC transfected with empty plasmid expression was not detected. CONCLUSIONS: Recombinant Eukaryotic expression plasmid pcDNA3.1-Shh is successfully detected in rat MSC. It may provide experimental rationales for the future gene therapy. PMID- 22781302 TI - [Effects of hypoxic preconditioning on the migration of bone marrow derived mesenchymal stem cells]. AB - OBJECTIVE: To explore the effects and probable mechanism of CoCl2-induced hypoxic preconditioning on the migration of bone marrow derived mesenchymal stem cells (BMSC). METHODS: BMSC were cultured by whole bone marrow adherence and identified by surface markers (CD29, CD90 and CD45) with flow cytometry (FCM). The methods of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and FCM were applied to establish the model of CoCl2-induced hypoxic preconditioning. The migratory capacity of BMSC with hypoxic preconditioning was analyzed by the assays of scratch wound healing and transwell migration. The protein and mRNA expressions of HIF-1alpha and CXCR4 of BMSC were detected by Western blot and real-time polymerase chain reaction (PCR). After silencing HIF-1alpha by siRNA technique and blocking CXCR4 by its antagonist AMD3100, the changes of migratory capacity of BMSC were also tested. RESULTS: Cultured BMSC were uniformly positive for CD29 and CD90 and negative for CD 45. According to the results of MTT and FCM, 200 umol/L CoCl2 and 24 h culture time was the ideal hypoxic preconditioning model of BMSC. The migratory capacity of BMSC in hypoxic preconditioning group was higher than the one in control group (scratch wound healing assay: (0.396 +/- 0.018) mm vs (0.200 +/- 0.011) mm, transwell migration assay: 21.0 +/- 4.5 vs 8.5 +/- 1.7, both P < 0.05). The protein and mRNA levels of HIF-1alpha and CXCR4 of BMSC in hypoxic preconditioning group were significantly higher than in control group. After silencing HIF-1alpha or blocking CXCR4 by AMD3100, the migratory capacity of BMSC in hypoxic preconditioning group decreased and had no difference with the control group. CONCLUSIONS: Hypoxic preconditioning may enhance the migratory capacity of BMSC in vitro. And it is partially attributable to the up regulation of HIF-1alpha/CXCR4 axis after preconditioning. PMID- 22781303 TI - Hypoxia-inducible factor (HIF1alpha) gene expression in human shock states. AB - INTRODUCTION: Hypoxia-inducible factor-1 (HIF1) controls the expression of genes involved in the cellular response to hypoxia. No information is available on its expression in critically ill patients. Thus, we designed the first clinical study in order to evaluate the role of HIF1alpha as a prognosis marker in patients with shock. METHODS: 50 consecutive adult patients with shock and 11 healthy volunteers were prospectively included. RNA was extracted from whole blood samples and expression of HIF1alpha was assessed over the first 4 hours of shock. The primary objective was to assess HIF1alpha as a prognostic marker in shock. Secondary objectives were to evaluate the role of HIF1alpha as a diagnostic and follow-up marker. Patient survival was evaluated at day 28. RESULTS: The causes of shock were sepsis (78%), hemorrhage (18%), and cardiac dysfunction (4%). The HIF1alpha expression was significantly higher in the shock patients than in the healthy volunteers (121 [72-168] vs. 48 [38-54] normalized copies, p < 0.01), whatever the measured isoforms. It was similar in non-survivors and survivors (108 [range 84-183] vs. 121 [range 72-185] normalized copies, p = 0.92), and did not significantly change within the study period. CONCLUSIONS: The present study is the first to demonstrate the increased expression of HIF1alpha in patients with shock. Further studies are needed to clarify the potential association with outcome. Our findings reinforce the value of monitoring plasma lactate levels to guide the treatment of shock. PMID- 22781304 TI - Assessing the effects of multiple stressors on the functioning of Mediterranean rivers using poplar wood breakdown. AB - Mediterranean rivers in the Iberian Peninsula are being increasingly affected by human activities, which threaten their ecological status. A clear picture of how do these multiple stressors affect river ecosystem functioning is still lacking. We addressed this question by measuring a key ecosystem process, namely breakdown of organic matter, at 66 sites distributed across Mediterranean Spain. We performed breakdown experiments by measuring the mass lost by wood sticks for 54 to 106 days. Additionally, we gathered data on physico-chemical, biological and geomorphological characteristics of study sites. Study sites spanned a broad range of environmental characteristics and breakdown rates varied fiftyfold across sites. No clear geographic patterns were found between or within basins. 90th quantile regressions performed to link breakdown rates with environmental characteristics included the following 7 variables in the model, in decreasing order of importance: altitude, water content in phosphorus, catchment area, toxicity, invertebrate-based biotic index, riparian buffer width, and diatom based quality index. Breakdown rate was systematically low in high-altitude rivers with few human impacts, but showed a high variability in areas affected by human activity. This increase in variability is the result of the influence of multiple stressors acting simultaneously, as some of these can promote whereas others slow down the breakdown of organic matter. Therefore, stick breakdown gives information on the intensity of a key ecosystem process, which would otherwise be very difficult to predict based on environmental variables. PMID- 22781305 TI - Regulatory T cells are the most important determinant factor of hepatitis B infection prognosis: a systematic review and meta-analysis. AB - INTRODUCTION: Association of increased levels of CD4(+)CD25(+) regulatory T cells (Tregs) with impaired immune response and hepatitis B infection progression has been proposed. For determination of Tregs various effects among hepatitis B infected patients we performed a meta-analysis of the available literature. METHODS: Current content, abstract books of congresses, and electronic databases were searched. Critical appraisal has been done. According to the result of heterogeneity tests (Q, I-squared, and Tau-squared), we used fix/random model for analysis. RESULT: Twelve studies that fulfilled inclusion criteria entered to analysis. Pooled estimation of reported results showed that CD4(+)CD25(+) Tregs have higher expression of forkhead box P3 (FoxP3) versus CD4(+)CD25(-) Tregs, odd ratio (OR) was 31.49 (95% Confidence Intervals (CI): 5.09-194.94). Tregs level among chronic hepatitis B (CHB) patients was 77% (OR=1.77 95% CI: 1.43-2.19) higher than healthy controls. Patients with more than 10,000,000 HBV copies/ml have higher level of Tregs (OR: 1.24 95% CI: 1.08-1.41) comparing subjects with less than that. CHB patients have increased level of Tregs versus acute hepatitis B patients (OR=1.33 95% CI: 1.16-1.52). CD8 cells activity increased significantly after depletion of circulating Tregs (OR=1.93 CI: 1.37-2.73). Also, Tregs reduce response to treatment and non-responders to INF-alpha had higher level of Tregs (OR=1.60 95% CI: 1.09-2.36). In addition, Tregs increase risk of hepatocellular carcinoma (HCC) (OR=1.36 95%CI: 1.10-1.69). CONCLUSION: Tregs influence HBV infected patients in various states. Tregs determine the disease prognosis by leading to infection progression and impairing immune response. So, Tregs are therapeutic target for immunotherapy of HBV infection. PMID- 22781306 TI - Failure of the vaccination campaign against A(H1N1) influenza in pregnant women in France: results from a national survey. AB - BACKGROUND AND OBJECTIVE: Pregnant women were a priority group for vaccination during the 2009 A(H1N1) influenza pandemic. In France, vaccination was organized in ad hoc centers. Women received vouchers by mail and were given a non adjuvanted vaccine. Our objective was to assess the national vaccination rate among pregnant women and to determine the association of vaccination with maternal characteristics, prenatal care, and pregnancy-related health behaviors. METHOD: Data came from a national representative sample of women who gave birth in March 2010 (N=13 453) and were interviewed in the hospital before discharge; they were in the second trimester of pregnancy during the vaccination campaign. Associations between vaccination and socio-demographic and medical characteristics, region of residence, care providers, and preventive behaviors were assessed with bivariable analyses and logistic regression models. RESULTS: Vaccine coverage was 29.3% (95% CI: 28.6-30.1). The main reason for not being vaccinated was that women did not want this immunization (91%). In adjusted analyses, vaccination was more frequent in women who were older, employed, born in France, with a parity of 1 or 2 and specific favourable health behaviors. The adjusted odds ratio for women with a postgraduate educational level was 4.1 (95% CI: 3.5-4.8) compared to those who did not complete high school. Women with additional risk factors for complications from A(H1N1) infection had a vaccination rate similar to that of other women. CONCLUSION: The vaccination campaign resulted in poor vaccination coverage, strong social inequalities, and no special protection for pregnant women at the highest risk of complications. These findings provide essential information for the organization of future vaccination campaigns. PMID- 22781307 TI - Dimethylamine borane dehydrogenation chemistry: syntheses, X-ray and neutron diffraction studies of 18-electron aminoborane and 14-electron aminoboryl complexes. AB - The reactions of Me(2)NH.BH(3) with cationic Rh(III) and Ir(III) complexes have been shown to generate the 18-electron aminoborane adduct [Ir(IMes)(2)(H)(2){kappa(2)-H(2)BNMe(2))](+) and the remarkable 14-electron aminoboryl complex [Rh(IMes)(2)(H)-{B(H)NMe(2))](+). Neutron diffraction studies have been used for the first time to define H-atom locations in metal complexes of this type formed under catalytic conditions. PMID- 22781308 TI - Molecular insights into arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 missense mutations. AB - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disorder mainly caused by dominant mutations in several components of the cardiac desmosome including plakophilin-2 (PKP2), the most prevalent disease gene. Little is known about the underlying genetic and molecular mechanisms of missense mutations located in the armadillo (ARM) domains of PKP2, as well as their consequences on human cardiac pathology. METHODS AND RESULTS: We focused on in vivo and in vitro studies of the PKP2 founder mutation c.2386T>C (p.C796R), and demonstrated in cardiac tissue from 2 related mutation carriers a patchy expression pattern ranging from unchanged to totally absent immunoreactive signals of PKP2 and other desmosomal proteins. In vitro expression analysis of mutant PKP2 in cardiac derived HL-1 cells revealed unstable proteins that fail to interact with desmoplakin and are targeted by degradation involving calpain proteases. Bacterial expression, crystallization, and structural modeling of mutated proteins impacting different ARM domains and helices of PKP2 confirmed their instability and degradation, resulting in the same remaining protein fragment that was crystallized and used to model the entire ARM domain of PKP2. CONCLUSIONS: The p.C796R and other ARVC-related PKP2 mutations indicate loss of function effects by intrinsic instability and calpain proteases mediated degradation in in vitro model systems, suggesting haploinsufficiency as the most likely cause for the genesis of dominant ARVC due to mutations in PKP2. PMID- 22781309 TI - Blood pressure reduction following prolonged exercise in young and middle-aged endurance athletes. AB - BACKGROUND: Previous studies examining the relationship between exercise dose and post-exercise hypotension (PEH) have employed a limited range of exercise duration and subject age. We extended the dose-response curve by studying two intensities of prolonged exercise that may produce a greater magnitude of PEH and reveal age differences in the exercise dose-response relationship for PEH. METHODS: Two groups of healthy recreational endurance athletes were studied: Young (n = 17; age 28 +/- 1.1 years) and middle-aged participants (n = 18; 52 +/- 0.90 years). They performed on separate occasions, 120 min of prolonged exercise (running) at moderate (60% VO2max) and high intensities (80% VO2max). RESULTS: PEH after 1 hour of recovery was similar within each age group for either exercise intensity, but was significantly greater in the middle-aged group (moderate intensity, -12.3 +/- 1.6 mmHg; high intensity, -15.1 +/- 1.7 mmHg) compared with the young group (moderate intensity, -1.2 +/- 1.7 mmHg; high intensity, -5.7 +/- 2.5 mmHg; p < 0.05). Stepwise regression showed that baseline blood pressure but not age was significantly related to the degree of PEH. Thus, the greater PEH seen in the middle-aged group is attributed to their higher baseline blood pressure (124 +/- 3.0/79 +/- 2.0 mmHg) than the young group (111 +/- 2.0/69 +/- 1.8 mmHg). A reduced total peripheral resistance following exercise was the primary contributor to PEH across both age groups and exercise intensities. CONCLUSIONS: We conclude that prolonged exercise induces a significant PEH regardless of exercise intensity. PMID- 22781310 TI - Chemoenzymatic synthesis and biological evaluation of 2- and 3-hydroxypyridine derivatives against Leishmania mexicana. AB - A series of hydroxyalkyl and acyloxyalkyl derivatives of 2- and 3-hydroxypyridine was synthesized and their biological activity was evaluated as growth inhibitors of protozoan Leishmania mexicana. Thirty novel compounds were obtained through a chemoenzymatic methodology in two reaction steps. The influence of various reaction parameters in the enzymatic step, such as enzyme source, acylating agent/substrate ratio, enzyme/substrate ratio, solvent and temperature, was studied. Some of the evaluated compounds showed a remarkable activity as Leishmania mexicana growth inhibitors, obtaining the best results with the acetylated derivatives. The advantages showed by the enzymatic methodology, such as mild reaction conditions and low environmental impact, make the biocatalysis a convenient way to prepare these derivatives of substituted pyridines with application as potential antiparasitic agents. PMID- 22781311 TI - Differential functional connectivity within an emotion regulation neural network among individuals resilient and susceptible to the depressogenic effects of early life stress. AB - BACKGROUND: Early life stress (ELS) is a significant risk factor for depression. The effects of ELS exposure on neural network organization have not been differentiated from the effect of depression. Furthermore, many individuals exposed to ELS do not develop depression, yet the network organization patterns differentiating resiliency versus susceptibility to the depressogenic effects of ELS are not clear. METHOD: Women aged 18-44 years with either a history of ELS and no history of depression (n = 7), a history of ELS and current or past depression (n = 19), or a history of neither ELS nor depression (n = 12) underwent a resting-state 3-T functional magnetic resonance imaging (fMRI) scan. An emotion regulation brain network consisting of 21 nodes was described using graph analyses and compared between groups. RESULTS: Group differences in network topology involved decreased global connectivity and hub-like properties for the right ventrolateral prefrontal cortex (vlPFC) and decreased local network connectivity for the dorsal anterior cingulate cortex (dACC) among resilient individuals. Decreased local connectivity and increased hub-like properties of the left amygdala, decreased hub-like properties of the dACC and decreased local connectivity of the left vlPFC were observed among susceptible individuals. Regression analyses suggested that the severity of ELS (measured by self-report) correlated negatively with global connectivity and hub-like qualities for the left dorsolateral PFC (dlPFC). CONCLUSIONS: These preliminary results suggest functional neural connectivity patterns specific to ELS exposure and resiliency versus susceptibility to the depressogenic effects of ELS exposure. PMID- 22781312 TI - A systematic review of healthcare applications for smartphones. AB - BACKGROUND: Advanced mobile communications and portable computation are now combined in handheld devices called "smartphones", which are also capable of running third-party software. The number of smartphone users is growing rapidly, including among healthcare professionals. The purpose of this study was to classify smartphone-based healthcare technologies as discussed in academic literature according to their functionalities, and summarize articles in each category. METHODS: In April 2011, MEDLINE was searched to identify articles that discussed the design, development, evaluation, or use of smartphone-based software for healthcare professionals, medical or nursing students, or patients. A total of 55 articles discussing 83 applications were selected for this study from 2,894 articles initially obtained from the MEDLINE searches. RESULTS: A total of 83 applications were documented: 57 applications for healthcare professionals focusing on disease diagnosis (21), drug reference (6), medical calculators (8), literature search (6), clinical communication (3), Hospital Information System (HIS) client applications (4), medical training (2) and general healthcare applications (7); 11 applications for medical or nursing students focusing on medical education; and 15 applications for patients focusing on disease management with chronic illness (6), ENT-related (4), fall-related (3), and two other conditions (2). The disease diagnosis, drug reference, and medical calculator applications were reported as most useful by healthcare professionals and medical or nursing students. CONCLUSIONS: Many medical applications for smartphones have been developed and widely used by health professionals and patients. The use of smartphones is getting more attention in healthcare day by day. Medical applications make smartphones useful tools in the practice of evidence-based medicine at the point of care, in addition to their use in mobile clinical communication. Also, smartphones can play a very important role in patient education, disease self-management, and remote monitoring of patients. PMID- 22781314 TI - MRI of mass transport in porous media: drying and sorption processes. PMID- 22781313 TI - The effect of anxiety on respiratory sensory gating measured by respiratory related evoked potentials. AB - Respiratory sensory gating is evidenced by decreased amplitudes of the respiratory-related evoked potentials (RREP) N1 peak for the second (S2) compared to the first occlusion (S1) when two paired occlusions are presented with a 500 millisecond (ms) inter-stimulus-interval during one inspiration. Because anxiety is prevalent in respiratory diseases and associated with altered respiratory perception, we tested whether anxiety can modulate individuals' respiratory neural gating mechanism. By using high-density EEG, RREPs were measured in a paired inspiratory occlusion paradigm in 11 low and 10 higher anxious individuals with normal lung function. The N1 peak gating S2/S1 ratio and the N1 S2 amplitudes were greater in higher compared to low anxious individuals (p's<0.05). In addition, higher anxiety levels were correlated with greater S2/S1 ratios (r=0.54, p<0.05) and S2 amplitudes (r=-0.49, p<0.05). The results demonstrate that anxiety is associated with reduced respiratory sensory gating which might underlie altered respiratory symptom perception in anxious individuals. PMID- 22781315 TI - Skeletal muscle lipid metabolism studied by advanced magnetic resonance spectroscopy. PMID- 22781317 TI - DXA, bioelectrical impedance, ultrasonography and biometry for the estimation of fat and lean mass in cats during weight loss. AB - BACKGROUND: Few equations have been developed in veterinary medicine compared to human medicine to predict body composition. The present study was done to evaluate the influence of weight loss on biometry (BIO), bioimpedance analysis (BIA) and ultrasonography (US) in cats, proposing equations to estimate fat (FM) and lean (LM) body mass, as compared to dual energy x-ray absorptiometry (DXA) as the referenced method. For this were used 16 gonadectomized obese cats (8 males and 8 females) in a weight loss program. DXA, BIO, BIA and US were performed in the obese state (T0; obese animals), after 10% of weight loss (T1) and after 20% of weight loss (T2). Stepwise regression was used to analyze the relationship between the dependent variables (FM, LM) determined by DXA and the independent variables obtained by BIO, BIA and US. The better models chosen were evaluated by a simple regression analysis and means predicted vs. determined by DXA were compared to verify the accuracy of the equations. RESULTS: The independent variables determined by BIO, BIA and US that best correlated (p < 0.005) with the dependent variables (FM and LM) were BW (body weight), TC (thoracic circumference), PC (pelvic circumference), R (resistance) and SFLT (subcutaneous fat layer thickness). Using Mallows'Cp statistics, p value and r2, 19 equations were selected (12 for FM, 7 for LM); however, only 7 equations accurately predicted FM and one LM of cats. CONCLUSIONS: The equations with two variables are better to use because they are effective and will be an alternative method to estimate body composition in the clinical routine. For estimated lean mass the equations using body weight associated with biometrics measures can be proposed. For estimated fat mass the equations using body weight associated with bioimpedance analysis can be proposed. PMID- 22781316 TI - Lycorine hydrochloride inhibits metastatic melanoma cell-dominant vasculogenic mimicry. AB - Melanoma cells actively participate in tumor angiogenesis and vasculogenic mimicry. However, anti-angiogenic therapy in patients with melanoma has not shown a significant survival gain. Thus, new anti-melanoma angiogenic and vasculogenic drugs are highly desired. Using the metastatic melanoma cell line C8161 as a model, we explored melanoma vasculogenic inhibitors and found that lycorine hydrochloride (LH) effectively suppressed C8161 cell-dominant formation of capillary-like tubes in vitro and generation of tumor blood vessels in vivo with low toxicity. Mechanistic studies revealed that LH markedly hindered expression of VE-cadherin in C8161 cells, but did not affect expression of six other important angiogenic and vasculogenic genes. Luciferase assays showed that LH significantly impeded promoter activity of the VE-cadherin gene in a dose dependent manner. Together, these data suggest that LH inhibits melanoma C8161 cell-dominant vasculogenic mimicry by reducing VE-cadherin gene expression and diminishing cell surface exposure of the protein. PMID- 22781318 TI - [Analysis of distribution characteristics and drug resistance of 2748 strains of pathogens isolated from burn patients]. AB - OBJECTIVE: To provide epidemiological data of the distribution characteristics and drug resistance of the pathogens isolated from burn patients in recent years for guiding rational use of antibiotics in clinic. METHODS: Totally 2748 strains of pathogens were isolated from 1977 specimens (blood, catheter, wound excretion, etc.) collected from 478 patients hospitalized in Institute of Burn Research of Southwest Hospital from March 2003 to June 2011. After being identified by API strips, drug resistance of the 2748 isolated pathogens to 55 commonly-used antibiotics including gentamicin, tobramycin, piperacillin, amikacin, etc. was tested by K-B paper disk diffusion method. The WHONET 5.3 software was used to analyze the following subjects: the distribution of the pathogens with different types and different sources each year, the changes in drug-resistant rates of Gram negative bacilli, Gram positive cocci, and fungi to several antibiotics, and the changes in sensitive rates of Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), Acinetobacter baumannii (AB), Candida albicans (CA) to several antibiotics. RESULTS: Among 2748 strains of pathogens, 1879 strains of Gram negative bacilli accounted for 68.38%, 628 strains of Gram positive cocci accounted for 22.85%, and 241 strains of fungi accounted for 8.77%. The isolation rate of strains from wound excretion ranked the first (1022 strains accounted for 37.19%), followed by those from respiratory tract (995 strains accounted for 36.21%) and blood (421 strains accounted for 15.32%). Strains isolated from other types of specimens were rare. Isolation rate of PA ranked the first (996 strains accounted for 36.24%), followed by SA (495 strains accounted for 18.01%) and AB (395 strains accounted for 14.37%). Isolation rate of AB showed a trend of increase year by year, but that of SA presented the opposite trend. Isolation rate of PA was quite stable. There were 484 strains of methicillin resistant SA among Staphylococci, accounting for 17.61%. Resistant rates of PA and AB to polymyxin B and polymyxin E were below 30.00%, and those of PA and AB to other antibiotics, such as the third generation cephalosporins, beta-lactams, aminoglycosides, and quinolones, were from 57.91% to 100.00%. Resistant rate of AB to minocycline was 39.68%. From 2004 to 2011, sensitive rate of PA to quinolone antibiotics showed an increasing trend year by year, but that of AB to minocycline, netilmicin, imipenem, meropenem, tobramycin, and cefoperazone/sulbactam presented the opposite trend. Resistant rates of Enterococcus faecalis, Enterococcus faecium, and SA to teicoplanin and linezolid were less than 10.00%. Resistant rate of SA, Staphylococcus epidermidis and Enterococcus faecium to vancomycin was 0. Resistant rates of SA to quinupristin/dalfopristin, minocycline, fusidic acid, and compound sulfamethoxazole were low, respectively 0.82%, 9.35%, 2.21%, and 31.85%. Sensitive rates of SA to erythromycin, clindamycin, compound sulfamethoxazole, tetracycline, and minocycline showed an increasing trend year by year. Both infection rate and resistant rate of fungi were low. The resistant rates of CA to 5 kinds of antibiotics were less than 15.00%. The sensitive rate of CA to 5 flucytosine declined slightly, and those of CA to the other 4 antibiotics showed an increasing trend year by year. CONCLUSIONS: The three dominant pathogens that cause infection in burn patients hospitalized in Institute of Burn Research of Southwest Hospital in recent years are PA, SA, and AB in order. PA and AB are outstandingly multidrug-resistant among the isolated strains. AB might replace PA as the main pathogenic bacterium that cause the death of burn patients with infection. PMID- 22781319 TI - [Analysis of resistance phenotype and homology of Klebsiella pneumoniae in burn patients]. AB - OBJECTIVE: To study the resistance phenotype and homology of Klebsiella pneumoniae (KPN) in burn patients with infection. METHODS: Fifty-four strains of KPN were isolated from wound excretion, blood, sputum, venous catheter, feces, and oral cavity of patients hospitalized in Institute of Burn Research of Southwest Hospital (briefly called our institute) from January 2007 to June 2011. Drug resistance of the 54 strains of KPN to 18 antibiotics commonly used in clinic, including ampicillin, ticarcillin, etc, was tested by K-B paper disk diffusion method after being identified. Extended-spectrum beta-lactamase (ESBL) producing KPN was screened based on the drug resistance result. The positive rates of drug-resistant genes SHV, TEM, and CTX-M of the ESBL-producing KPN were detected by polymerase chain reaction. The homology of the ESBL-producing KPN was analyzed by pulse field gel electrophoresis and clustering methodology. The homology of ESBL-producing KPN isolated in each year was analyzed too. RESULTS: (1) The sensitive rate of the 54 strains of KPN to imipenem, meropenem, and ertapenem was respectively 96.30%, 92.59%, and 81.48%, that of these strains to cefotetan and cefoxitin was respectively 70.37% and 64.81%, and that of these strains to ceftazidime was 57.41%. The sensitive rates of the 54 strains of KPN to the other antibiotics were all lower than 40.00%. (2) Twenty-six ESBL producing KPN strains were screened and the positive rate of SHV, TEM, and CTX-M was 96.15% (25/26), 76.92% (20/26), and 57.69% (15/26), respectively. Detection rate of ESBL-producing KPN strains carrying three genes at the same time was 42.31% (11/26), that of these strains carrying both SHV and TEM was 34.62% (9/26), and those of these strains carrying only a single gene were all less than 10.00%. (3) The twenty-six ESBL-producing KPN were classified into 9 gene types, with 30.77% (8/26) in type A, 19.23% (5/26) in type B, 15.38% (4/26) in type C, 11.54% (3/26) in type D, 7.69% (2/26) in type E, and the rest four strains respectively in type F, G, H, I [3.85% (1/26)]. (4) The major gene type of ESBL producing KPN in the year of 2007 and 2010 was type A, respectively accounting for 2/3 and 1/2, while that in the year of 2009 was type B, accounting for 1/2. The three strains in 2008 was respectively in type C, E, and F. The four strains in 2011 was respectively in type A, D, H, I. CONCLUSIONS: KPN in burn patients with infection in our institute are highly resistant to commonly used antibiotics in clinic, but carbapenems antibiotics can be used for the treatment. Most of the ESBL-producing KPN strains carry two or three drug-resistant genes, and the main gene type of them is type A. PMID- 22781320 TI - [Changes in expression of gene aba I in biofilm of Acinetobacter baumannii strains isolated from burn patients]. AB - OBJECTIVE: To study the changes in expression of quorum sensing gene aba I in Acinetobacter baumannii (AB) strains isolated from burn patients during biofilm formation process, and its influences on the extracellular matrix of biofilm and drug resistance of AB. METHODS: Six drug-resistant and five drug-sensitive AB strains isolated from wound excretion, blood and venous catheter were collected from burn patients hospitalized in Ruijin hospital of Shanghai Jiao Tong University School of Medicine from January to October 2011. The AB standard strain ATCC 19606 was used as control. (1) Clinical strains and standard strain were normally cultured 10, 24, and 48 h respectively in vitro. The bacteria samples were stained with propidium iodide to measure biofilm thickness with confocal laser scanning microscope. (2) Clinical strains and standard strain were cultured in tubes 10, 24, and 48 h respectively in vitro under shaking condition. The bacteria floating in the medium were regarded as free bacteria, while those adhered to the tube wall as the bacteria within biofilm (biofilm bacteria). Relative expression value of genes aba I and pgaB was detected by real-time fluorescent quantitative PCR with the expression value of the standard strain set at 1. Data were processed with analysis of variance. RESULTS: (1) At post culture hour (PCH) 10, 24, 48, biofilm thickness of clinical strains was thicker than that of standard strain; biofilm thickness of drug-resistant strains [(28.8 +/- 0.6), (31.7 +/- 1.1), and (38.1 +/- 3.1) um] was respectively thicker than that of drug-sensitive strains [(17.1 +/- 0.4), (20.1 +/- 1.6), and (25.8 +/- 1.7) um, with F value respectively 1274.38, 206.60, and 61.73, P values all below 0.05]. (2) Biofilm bacteria: at PCH 10, 24, 48, expression values of aba I in drug resistant strains (6.6 +/- 1.7, 25.7 +/- 3.5, 9.8 +/- 3.6) were much higher than those of drug-sensitive strains (2.7 +/- 1.0, 15.0 +/- 3.5, 4.7 +/- 3.2, with F value respectively 21.82, 25.24, and 6.22, P values all below 0.05); expression values of pgaB in drug-resistant strains (37.4 +/- 1.1, 44.5 +/- 3.6, 33.1 +/- 11.5) were obviously higher than those of drug-sensitive strains (14.6 +/- 0.8, 20.0 +/- 6.9, 18.7 +/- 6.8, with F value respectively 1488.44, 57.26, and 6.01, P values all below 0.05). (3) Free bacteria: at PCH 10, 24, 48, there was no significant statistical difference between drug-resistant strains and drug sensitive strains in expression value of aba I (with F value respectively 0.24, 2.33, and 0.11, P values all above 0.05); expression values of pgaB in drug resistant strains (13.8 +/- 3.8, 12.5 +/- 2.9, 23.7 +/- 2.1) were obviously higher than those of drug-sensitive strains (7.0 +/- 5.9, 5.0 +/- 1.3, 15.6 +/- 6.7, with F value respectively 5.44, 28.42, and 7.76, P values all below 0.05). (4) Comparison between biofilm bacteria and free bacteria in resistant strains: expression value of aba I in biofilm bacteria at each time point was respectively higher than that of free bacteria (with F value respectively 43.69, 286.61, and 9.98, P values all below 0.05); expression values of pgaB in biofilm bacteria at PCH 10, 24 were higher than those in free bacteria (with F value respectively 214.26 and 283.20, P values below 0.05). (5) Comparison between biofilm bacteria and free bacteria in sensitive strains: expression value of aba I in BF bacteria at PCH 24 was higher than that of free bacteria (F = 70.28, P < 0.05); expression values of pgaB in biofilm bacteria at PCH 10, 24 were higher than those of free bacteria (with F value respectively 8.03 and 22.62, P values below 0.05). CONCLUSIONS: During biofilm formation process, the increasing expression of quorum sensing gene aba I in drug-resistant AB strains isolated from burn patients may up-regulate the expression of gene pgaB, which leads to high production of extracellular matrix and biofilm formation, and enhances drug resistance of AB. PMID- 22781321 TI - [Effects of topical agents for burns on Acinetobacter baumannii within biofilm]. AB - OBJECTIVE: To observe the antimicrobial activity of topical agents commonly used for burns on Acinetobacter baumannii (AB) in both free and biofilm states, and their synergistic effect with ambroxol on AB within biofilm. METHODS: Eleven AB strains were isolated from wound excretion, respiratory tract, and blood of patients hospitalized in our hospital from August 2005 to April 2007. (1) The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of mafenide acetate and chlorhexidine acetate to free AB (including drug resistant, drug-sensitive, and standard strains) were determined by dilution method. (2) AB was cultured with LB or TSB medium for 12, 24, and 48 h to form biofilm, and it was treated with above-mentioned two topical agents in MBC (mafenide group and chlorhexidine group) for 30 min. Biofilm not treated by topical agent was used as control group. The biofilm thickness was determined with confocal laser scanning microscope. The proportion of living bacteria in biofilm was calculated. AB biofilm in each topical agent group was mixed and inoculated into LB culture dish to observe the growth of bacteria. (3) AB was cultured with LB medium for 48 h to form biofilm, which was respectively treated by above-mentioned two topical agents in MBC (mafenide group and chlorhexidine group) and combination of each topical agent with 3.75 mg/mL ambroxol solution (ambroxol + mafenide group and ambroxol + chlorhexidine group) for 30 min. Biofilm not treated by topical agents was used as control group. Growth of bacteria in biofilm was detected with MTT method (denoted as absorbance value). Data were processed with one-way analysis of variance and LSD-t test. RESULTS: (1) MIC of mafenide acetate and chlorhexidine acetate for free AB was respectively 25.00 mg/mL and 0.03 mg/mL. MBC of both agents for free AB was the same as their MIC. (2) Among three groups, the thickness of biofilm of sensitive AB was thicker than that of drug-resistant bacteria at most of the time points. Compared with those in control group, biofilm thickness and proportion of living bacteria in biofilm were slightly decreased in mafenide and chlorhexidine groups. The growth of bacteria was abundant in each group. (3) Absorbance value of drug resistant bacteria in control, mafenide, and chlorhexidine groups was respectively 0.776 +/- 0.071, 0.625 +/- 0.063, and 0.420 +/- 0.068. Absorbance value of drug-resistant bacteria in ambroxol + mafenide group (0.174 +/- 0.089) was significantly lower than that of control group (t = 11.823, P = 0.000) and mafenide group (t = 9.248, P < 0.01). Absorbance value of ambroxol + chlorhexidine group (0.178 +/- 0.044) was significantly lower than that of control group (t = 16.009, P = 0.000) and chlorhexidine group (t = 6.681, P < 0.01). CONCLUSIONS: Drug-resistant AB forms biofilm readily, which prevents topical agents from killing the bacteria inside. Combined use of ambroxol with topical agents gives synergistic effect on killing AB in biofilm in the wound. PMID- 22781322 TI - [Changes in serum contents of interleukin-6 and interleukin-10 and their relation with occurrence of sepsis and prognosis of severely burned patients]. AB - OBJECTIVE: To observe the changes in serum contents of interleukin-6 (IL-6) and interleukin-10 (IL-10) in patients with severe burn injury, and to investigate their relation with occurrence of sepsis and prognosis of patients. METHODS: One hundred and sixty adult patients admitted into our hospital (1.0 +/- 6.0) h after injury during March 2007 to March 2011 with massive and severe burns were enrolled in the investigation. Patients were divided into non-sepsis group (NS, n = 112), sepsis-survival group (SS, n = 36), and sepsis-deceased group (SD, n = 12) based on the occurrence of sepsis and death. Sepsis occurred on post burn day (PBD) 9 +/- 5 in patients in the latter two groups. Patients died on PBD 18 +/- 4 in SD group. Twenty healthy adult volunteers were chosen as healthy control group (HC). The age of subjects for observation among four groups, and total burn area and full-thickness burn area of patients among NS, SS, and SD groups were compared. Serum was isolated from blood samples collected from each patient every day from day of admission till PBD 20 to determine the contents of IL-6 and IL-10 by ELISA, and the same determinations were done in HC group. Data of trial subjects were processed with one-way analysis of variance. Data of IL-6 and IL-10 contents were processed with analysis of variance of repeated measure data and SNK method (q test). RESULTS: (1) There was no significant statistical difference among four groups in age (F = 2.090, P > 0.05). Total burn areas of patients in SS and SD groups were significantly larger than that in NS group (q test, with P values both below 0.05), and total burn area of patients in SD group was obviously larger than that in SS group (q test, P < 0.05). Full-thickness burn areas of patients in SS and SD groups were significantly larger than that in NS group (q test, with P values both below 0.05). (2) Serum contents of IL-6 of patients in NS, SS, and SD groups from PBD 1 to 20 were obviously higher than that of volunteers in HC group. There was no significant statistical difference among NS, SS, and SD groups in serum contents of IL-6 from PBD 1 to 7 (with F value from 0.188 to 2.897, P values all above 0.05). Serum content of IL-6 of patients in NS group decreased from PBD 4. Serum content of IL-6 of patients in SS group decreased gradually from PBD 13, but that in SD group increased continuously at the same time points. Serum contents of IL-6 of patients in NS group [(262 +/- 25) pg/mL on PBD 8] were lower than those in SS group [(287 +/- 38) pg/mL on PBD 8, q test, P < 0.05] and SD group [(299 +/- 22) pg/mL on PBD 8, q test, P < 0.05] from PBD 8. Serum contents of IL-6 of patients in SS group [(300 +/- 33) pg/mL on PBD 13] were obviously lower than those in SD group [(338 +/- 22) pg/mL on PBD 13, q test, P < 0.05] from PBD 13. (3) Serum contents of IL 10 of patients in NS, SS, and SD groups were higher than that in HC group at each time point. There was no significant statistical difference among NS, SS, and SD groups in serum contents of IL-6 from PBD 1 to 5 (with F values from 1.802 to 2.538, P values all above 0.05). Serum content of IL-10 of patients in NS group was obviously lower than that of patients in SD group from PBD 6 (q test, P values all below 0.05). On PBD 8, serum content of IL-10 of patients in SS group [(54 +/- 19) pg/mL] was obviously lower than that in SD group [(91 +/- 23) pg/mL, q test, P < 0.05]. The sum of sensitivity (83.33%, 10/12) and specificity (91.67%, 33/36) minus 1 was maximum when the critical value of IL-10 content was set at 77 pg/mL based on the comparison between SS group and SD group in serum content of IL-10 on PBD 8. CONCLUSIONS: The occurrence and outcome of sepsis is related to burn area and depth when the patients are in similar age. Serum contents of IL-6 and IL-10 play important roles in the pathogenesis of sepsis after burn. IL-6 content in early stage shall not be used in predicting the prognosis of patients with sepsis. IL-10 continuously higher than 77 pg/mL in early stage forecasts unfavorable prognosis of patient. PMID- 22781323 TI - [Treatment of full-thickness electric burn of skull combined with cerebral contusion and intracranial infection]. AB - This article reports the treatment of a patient suffering from full-thickness electric burn of skull combined with cerebral contusion and intracranial infection to provide experience in treating such patients. Based on detailed analysis on patient's condition and CT results, several operations of surgery and anti-infection treatment were performed on the patient. The wounds healed 6 weeks after injury. The skull defect was repaired with three-dimensionally reconstructed titanium mesh of computer-aided design two years after wound healing. The treatment of full-thickness electric burn of skull combined with cerebral contusion was quite difficult. The timing and mode of operation were very important. Perioperative prevention and treatment of intracranial infection were essential to save the life of the patient. In the event of intracranial infection, effective systemic use of antibiotics, cerebrospinal fluid drainage, intrathecal injection of drugs, and the application of other comprehensive measures could ensure the success of treatment. PMID- 22781324 TI - [Changes in cytokines in lymph and T lymphocyte subsets in lymph node of burned rats]. AB - OBJECTIVE: To observe the effect of burn on cytokines in lymph and T lymphocyte subsets in lymph node of rats. METHODS: Eighteen Wistar rats were used in the experiment. One of the hind limbs of each rat was immersed in 70 degrees C hot water for 30 s to reproduce 4%TBSA deep partial-thickness scald model (burn group), while the other hind limb was immersed in 22 degrees C warm water for 30 s to simulate scald (sham injury group). On post injury hour (PIH) 6, 24, and 72, 6 rats were chosen according to the random number table. Lymph fluid in the lymph vessel of each animal (two groups) was obtained for determination of levels of tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by ELISA, and IFN-gamma/IL-4 ratio was calculated. Common iliac lymph node of each animal (two groups) was obtained for determination of ratios of CD4(+), CD8(+)T lymphocytes with flow cytometry, and CD4(+)/CD8(+) ratio was calculated. Data were processed with t test. RESULTS: (1) On PIH 6, 24, and 72, TNF-alpha level in burn group was respectively (51.6 +/- 5.4), (27.4 +/- 2.6), (23.0 +/- 2.7) pg/mL, which were significantly higher than those in sham injury group [(17.8 +/- 1.6), (16.4 +/- 1.2), (17.2 +/- 2.0) pg/mL, with t value respectively 15.346, 11.854, 4.189, P values all below 0.01]. (2) On PIH 6, 24, and 72, there was no significant statistical difference between burn group and sham injury group in IFN-gamma level (with t value respectively 2.059, -0.805, 0.415, P values all above 0.05); IL-4 level in burn group was respectively higher than that in sham injury group (with t value respectively 9.141, 11.669, 6.940, P values all below 0.01); IFN-gamma/IL-4 ratio in burn group (2.27 +/- 0.34, 1.54 +/- 0.19, 1.60 +/- 0.16) was respectively lower than that in sham injury group (3.33 +/- 0.25, 3.34 +/- 0.22, 2.52 +/- 0.24, with t value respectively -6.298, 11.313, -8.893, P values all below 0.01). (3) On PIH 6 and 24, there was no significant statistical difference between burn group and sham injury group in ratios of CD4(+) and CD8(+)T lymphocytes and also CD4(+)/CD8(+) ratio (with t values from -2.486 to -0.215, P values all above 0.05). On PIH 72, ratio of CD4(+)T lymphocytes and CD4(+)/CD8(+) ratio in burn group was respectively (38.6 +/- 2.3)% and 2.13 +/- 0.16, which were significantly lower than those in sham injury group [(48.9 +/- 2.9)% and 2.68 +/- 0.12, with t value respectively 7.551, -5.068, P values below 0.01]; there was no significant statistical difference between burn group and sham injury group in ratio of CD8(+)T lymphocytes (t = 0.845, P > 0.05). CONCLUSIONS: Burn may decrease IFN-gamma/IL-4 ratio in locally drained lymph and CD4(+)/CD8(+) ratio in locally drained lymph node of rat, which may indicate lowering of local immune function. PMID- 22781325 TI - [Biologic effect of nitric oxide on human epidermal stem cells in vitro]. AB - OBJECTIVE: To observe the effect of nitric oxide (NO) on adhesion, proliferation, and migration of human epidermal stem cells (ESC) in vitro. METHODS: ESC were isolated and cultured by the modified method of rapid attachment to type IV collagen. (1) Morphology of cells was observed under inverted phase-contrast microscope. Expression levels of integrin beta(1) and cytokeratin 19 (CK19) of cells were determined by Western blotting and immunofluorescence staining. (2) After being treated with scratching, ESC adhered to the wall was respectively treated with nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) in the concentration of 1, 10, 100, 500 umol/L. ESC without treatment of SNAP was used as control. The migration rate of ESC was detected at post scratching hour (PSH) 12 and 24. The chemotaxis of ESC (treated with SNAP in above-mentioned concentration) was tested by Transwell assay, and the transferred cell number was counted. (3) ESC was respectively treated with SNAP in the concentration of 10, 100, 500 umol/L for 1 h. ESC without treatment of SNAP was used as control. The adhesion of ESC was detected with adhesion test, and the inhibition rate of adhesion was calculated. The proliferation of ESC (denoted as absorbance value) was determined by microplate reader at post-treatment hour (PTH) 0, 12, 24, 48. Data were processed with one-way analysis of variance and Dunnett t test. RESULTS: (1) Small clone formed on post culture days (PCD) 5 to 9. On PCD 10 to 14, cell proliferation sped up. CK19 and integrin beta(1) were detected to be expressed in the isolated cells. The cells were identified as ESC. (2) Compared with that of ESC without treatment of SNAP [(35.7 +/- 0.3)%, (45.7 +/- 5.0)%], migration of ESC treated with SNAP in the concentration from 1 to 100 umol/L was promoted at PSH 12 and 24. Migration rates of ESC treated with 100 umol/L SNAP were the highest [respectively (48.8 +/- 2.7)%, (82.1 +/- 15.8)%, with t value respectively 8.34, 5.10, P values both below 0.01]. The number of ESC transferred to membrane after being treated with 100 umol/L SNAP was significantly larger than that of ESC without treatment of SNAP (t = 9.24, P = 0.00). (3) Absorbance values of ESC treated with 100, 500 umol/L SNAP were obviously higher than that of ESC without treatment of SNAP (with t value respectively 4.30, 4.67, P values both equal to 0.00). Proliferation of ESC treated with 100, 500 umol/L SNAP was obviously stronger than that of cells without treatment of SNAP at PTH 24, 48 (with t values from 2.84 to 8.17, P values all below 0.05). CONCLUSIONS: Exogenous NO in suitable concentration can promote the migration of human ESC. Exogenous NO can inhibit the adhesion and promote the proliferation of human ESC in vitro. PMID- 22781326 TI - [Effects of myrrh extract on proliferation and collagen mRNA expression of human fibroblasts in vitro]. AB - OBJECTIVE: To observe the effects of myrrh extract on biological characteristics of human dermal fibroblasts (Fb), and to explore its possible mechanisms in promoting wound healing. METHODS: Normal Fb was isolated from human foreskin tissue and cultured in vitro. The third to fifth passages of Fb were used in the experiment. (1) Fb were planted onto 96-well plate and divided into control group, and 1 * 10(-4), 1 * 10(-3), 1 * 10(-2), 1 * 10(-1), 1, 10, 1 * 10(2) g/L myrrh water extract groups and myrrh ethanol extract groups according to the random number table. Fb in control group were cultured with DMEM medium containing 0.25% calf serum (briefly called low-concentration serum medium), and those in various concentrations of myrrh water extract and myrrh ethanol extract groups respectively with low-concentration serum medium containing corresponding concentration of 2 kinds of myrrh extract. After being cultured for 48 h, cell morphology was observed with inverted-phase contrast microscope, and Fb proliferation activity (denoted as absorbance value) was determined with MTT method. (2) Fb were respectively planted into flasks and dishes and divided into two groups according to the random number table. Fb in control group were cultured with low-concentration serum medium, and that in 1 g/L myrrh water extract group with low-concentration serum medium containing 1 g/L myrrh water extract. After being cultured for 72 h, Fb cell cycle and the type I and III collagen mRNA expression were respectively determined by flow cytometry and real time fluorescent quantitative PCR. Data were processed with LSD-t test. RESULTS: (1) Fb in all groups grew in long-spindle shape, but the cell fusion was much obvious in 1 g/L myrrh water extract group than in control group. Fb absorbance value in 1 * 10(-3), 1 * 10(-2), 1 * 10(-1), 1, 10 g/L myrrh water extract groups was respectively 0.378 +/- 0.032, 0.402 +/- 0.007, 0.390 +/- 0.038, 0.453 +/- 0.036, 0.390 +/- 0.037, all higher than that in control group (0.332 +/- 0.044, with t value respectively 2.24, 2.93, 2.69, 5.73, 2.71, P values all below 0.05). Compared with that in control group, Fb absorbance value in 1 * 10(-4) g/L myrrh water extract group was not statistically different (0.312 +/- 0.048, t = 2.84, P > 0.05), while that in 1 * 10(2) g/L myrrh water extract group was significantly lower (0.154 +/- 0.009, t = 7.17, P < 0.05). Fb absorbance values in 1 * 10(-3), 1 * 10(-1), 1, 10, 1 * 10(2) g/L myrrh ethanol extract groups were significantly lower than that in control group (with t values from 2.30 to 24.79, P values all below 0.05). (2) Compared with those in control group [(82.2 +/- 7.9)% and (13.3 +/- 2.3)%, (4.5 +/- 0.8)%], the percentage of cells in G0/G1 phase in 1 g/L myrrh water extract group was obviously decreased [(74.3 +/- 6.3)%, t = 6.77, P < 0.05], while those in S and G2/M phases increased [(16.6 +/- 3.4)%, (9.1 +/- 1.6)%, with t value respectively 7.53, 6.34, P values below 0.05]. Compared with those in control group (1.00 +/- 0.05, 1.00 +/- 0.06), the mRNA level of collagen III in 1 g/L myrrh water extract group was significantly up-regulated (1.38 +/- 0.12, t = 3.81, P < 0.01), while that of collagen I was not statistically different (0.89 +/- 0.08, t = 1.17, P > 0.05). CONCLUSIONS: Myrrh water extract can notably promote the proliferation of Fb, accelerate the cell cycle of Fb, and up-regulate the mRNA expression of type III collagen in Fb, which may be related to its mechanisms in promoting wound healing. PMID- 22781327 TI - [Relationship between activation of Rho kinase signal pathway and permeability of hypoxic vascular endothelial cells]. AB - OBJECTIVE: To investigate the relationship between activation of Rho kinase (ROCK) signal pathway and permeability of hypoxic vascular endothelial cells. METHODS: (1) Human vascular endothelial cell line VE cells were planted onto 6 well plates Transwell and divided into control group (without hypoxia treatment) and hypoxia for 1, 2, 3, 6, 12 h groups (exposed to 1%O2, 5%CO2, and 94%N2 for corresponding time) according to the random number table, with 5 wells in each group. The expression levels of ROCKI, ROCKII, myosin light chain phosphatase target subunit 1 (MYPT1) and phosphorylated MYPT1 (p-MYPT1), myosin light chain (MLC), p-MLC in cells were detected by Western blotting. The ratios of p MYPT1/MYPT1 and p-MLC/MLC were calculated. (2) VE cells were planted onto 24-well plates Transwell, and the monolayer cells were divided into control group (without hypoxia treatment) and hypoxia for 6 h group (exposed to 1% O(2), 5% CO(2), and 94% N(2) for 6 h) according to the random number table, with 5 wells in each group. Permeability of monolayer cells was determined by fluorescence spectrophotometer. Data were processed with one-way analysis of variance or t test, and Newman-Keuls method was used in paired comparison among groups. RESULTS: (1) ROCKI protein expression in control and hypoxia for 1, 2, 3, 6, 12 h groups was obviously 0.63 +/- 0.14 and 0.36 +/- 0.08, 1.25 +/- 0.21, 1.98 +/- 0.16, 1.49 +/- 0.38, 0.79 +/- 0.24 (F = 36.52, P < 0.01). ROCKI protein expression in hypoxia for 2, 3, 6 h groups were obviously higher than that in control group (with P values all below 0.01). (2) There was significant statistical difference among all groups in ROCKII protein expression (F = 17.84, P < 0.01). ROCKII protein expression in hypoxia for 2 h group (1.33 +/- 0.17) was significantly higher than that in control group (1.05 +/- 0.04, P < 0.01). (3) p MYPT1/MYPT1 ratio in control and hypoxia for 1, 2, 3, 6, 12 h groups was respectively 0.62 +/- 0.13 and 0.62 +/- 0.11, 0.65 +/- 0.10, 1.06 +/- 0.23, 1.37 +/- 0.16, 1.91 +/- 0.32 (F = 37.41, P < 0.01). p-MYPT1/MYPT1 ratio in hypoxia for 3, 6, 12 h groups were obviously higher than that in control group (with P values all below 0.01). (4) p-MLC/MLC ratio in control and hypoxia for 1, 2, 3, 6, 12 h groups was respectively 0.72 +/- 0.19 and 0.83 +/- 0.17, 0.91 +/- 0.15, 1.39 +/- 0.16, 2.02 +/- 0.15, 0.90 +/- 0.25 (F = 36.92, P < 0.01). p-MLC/MLC ratio in hypoxia for 3, 6 h groups were obviously higher than that in control group (with P values all below 0.01). (5) Permeability of VE monolayer in hypoxia for 6 h group (36.1 +/- 8.0) was obviously higher than that in control group (9.1 +/- 2.1, t = 7.30, P < 0.01). CONCLUSIONS: Activation of ROCK signal pathway may be involved in the pathogenesis of vascular endothelial cell hyperpermeability induced by hypoxia. PMID- 22781328 TI - [Effects of different ways in repairing scrotum of pigs with full-thickness burn on apoptosis and bcl-2 protein expression of spermatogenic cells]. AB - OBJECTIVE: To observe the effects of different ways in repairing scrotum of pigs with full-thickness burn on spermatogenesis of testis. METHODS: Twenty male Guizhou miniature pigs were divided into normal control (NC), natural-healing (NH), flap-repairing (FR), and skin-grafting (SG) groups according to the random number table, with 5 pigs in each group. Pigs in NC group were not subjected to any injury. Scrotum of pigs in the latter three groups were inflicted with full thickness burn. Wounds in NH group healed naturally. Wounds in FR group were repaired with inguinal region flap, and those in SG group with full-thickness skin from lower abdomen. Appearance of scrotum in the latter three groups was observed right after injury, and three months post injury or surgery (PIM or PSM). Specimens of testes of pigs in the latter three groups were obtained in PIM or PSM 3 to detect apoptosis of spermatogenic cells with TUNEL, and bcl-2 protein expression with immunohistochemistry. The same indexes were observed and determined in pigs of NC group. Data were processed with one-way analysis of variance and LSD test. RESULTS: (1) Scrotum of pigs in NC group had skin folds with contraction function. Scrotum of pigs became hard with a leathery appearance right after burn in the other three groups. In PIM or PSM 3, wounds of pigs in NH group healed with scar, and the testes were squeezed into inguinal region. Scrotal skin of pigs in FR group was thick with testes in the scrotum, and that of pigs in SG group was thin with testes in the scrotum. (2) Spermatogenic cells in each level in NC group were arranged regularly, with few apoptotic spermatocytes and spermatoblasts. In NH, FR, and SG groups, seminiferous epithelium was thinner with most of the spermatogenic cells showing apoptosis, and they were mainly spermatogonia and spermatocytes. Apoptotic index of spermatogenic cells in NH, FR, SG, and NC groups was respectively (46.3 +/- 3.3)%, (40.9 +/- 3.5)%, (20.6 +/- 2.3)%, (7.5 +/- 1.9)%, and the difference among them was statistically significant (F = 405.65, P < 0.01). There were significant statistical differences among the former three groups (with P values below 0.01). (3) bcl-2 protein expression in NH, FR, SG, and NC groups was respectively (52 +/ 5)%, (53 +/- 4)%, (64 +/- 5)%, (75 +/- 5)%, and the difference among them was statistically significant (F = 56.63, P < 0.01). There was no significant statistical difference in bcl-2 expression between NH group and FR group (P = 0.66), and it was lower in both groups as compared with SG group (with P values below 0.01). CONCLUSIONS: Either scar healing, flap transplantation, or SG in repairing scrotum with full-thickness burn in pigs inhibits spermatogenesis, but repair with SG produces less deleterious effect on the testis. PMID- 22781329 TI - [Advances in wound care theory and technology]. AB - This paper reviews the progress in wound care research at home and abroad in recent years in regard to the aspects of wound healing theory, development of occlusive dressings, and wound care technology, etc. Wound care methods are constantly updated along with the development of medical science and technology, as well as theory and practice of nursing. Clinical nursing staff should acquire the latest knowledge of wound care, treat patients with appropriate methods of dressing and cover materials according to their conditions, and make effort to promote nutritional state, alleviate pain, and promote psychological care of patients, thus to provide patients with integral and dynamic wound care. PMID- 22781331 TI - MRI measurement of angiogenesis and the therapeutic effect of acute marrow stromal cell administration on traumatic brain injury. AB - Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the therapeutic effect of acute administration of human bone marrow stromal cells (hMSCs) on traumatic brain injury (TBI) and to measure the temporal profile of angiogenesis after the injury with or without cell intervention. Male Wistar rats (300 to 350 g, n=18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline (n=9) or hMSCs in suspension (n=9, 3 * 10(6) hMSCs) 6 hours after TBI. In-vivo MRI acquisitions of T2-weighted imaging, cerebral blood flow (CBF), three-dimensional (3D) gradient echo imaging, and blood-to-brain transfer constant (Ki) of contrast agent were performed on all animals 2 days after injury and weekly for 6 weeks. Sensorimotor function and spatial learning were evaluated. Volumetric changes in the trauma-induced brain lesion and the lateral ventricles were tracked and quantified using T2 maps, and hemodynamic alteration and blood-brain barrier permeability were monitored by CBF and Ki, respectively. Our data show that transplantation of hMSCs 6 hours after TBI leads to reduced cerebral atrophy, early and enhanced cerebral tissue perfusion and improved functional outcome compared with controls. The hMSC treatment increases angiogenesis in the injured brain, which may promote neurologic recovery after TBI. PMID- 22781330 TI - Biology of intracranial aneurysms: role of inflammation. AB - Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intense investigation, our understanding of the mechanisms leading to aneurysm development, progression and rupture remain incompletely defined. An accumulating body of evidence implicates inflammation as a critical contributor to aneurysm pathogenesis. Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a pro-inflammatory phenotype. A later final common pathway appears to involve apoptosis of cellular constituents of the vessel wall. These changes result in degradation of the integrity of the vascular wall leading to aneurysmal dilation, progression and eventual rupture in certain aneurysms. Various aspects of the inflammatory response have been investigated as contributors to IA pathogenesis including leukocytes, complement, immunoglobulins, cytokines, and other humoral mediators. Furthermore, gene expression profiling of IA compared with control arteries has prominently featured differential expression of genes involved with immune response/inflammation. Preliminary data suggest that therapies targeting the inflammatory response may have efficacy in the future treatment of IA. Further investigation, however, is necessary to elucidate the precise role of inflammation in IA pathogenesis, which can be exploited to improve the prognosis of patients harboring IA. PMID- 22781332 TI - Identifying the neural correlates of executive functions in early cerebral microangiopathy: a combined VBM and DTI study. AB - Cerebral microangiopathy (CMA) has been associated with executive dysfunction and fronto-parietal neural network disruption. Advances in magnetic resonance imaging allow more detailed analyses of gray (e.g., voxel-based morphometry-VBM) and white matter (e.g., diffusion tensor imaging-DTI) than traditional visual rating scales. The current study investigated patients with early CMA and healthy control subjects with all three approaches. Neuropsychological assessment focused on executive functions, the cognitive domain most discussed in CMA. The DTI and age-related white matter changes rating scales revealed convergent results showing widespread white matter changes in early CMA. Correlations were found in frontal and parietal areas exclusively with speeded, but not with speed-corrected executive measures. The VBM analyses showed reduced gray matter in frontal areas. All three approaches confirmed the hypothesized fronto-parietal network disruption in early CMA. Innovative methods (DTI) converged with results from conventional methods (visual rating) while allowing greater spatial and tissue accuracy. They are thus valid additions to the analysis of neural correlates of cognitive dysfunction. We found a clear distinction between speeded and nonspeeded executive measures in relationship to imaging parameters. Cognitive slowing is related to disease severity in early CMA and therefore important for early diagnostics. PMID- 22781333 TI - Oxygen consumption and blood flow coupling in human motor cortex during intense finger tapping: implication for a role of lactate. AB - Rates of cerebral blood flow (CBF) and glucose consumption (CMR(glc)) rise in cerebral cortex during continuous stimulation, while the oxygen-glucose index (OGI) declines as an index of mismatched coupling of oxygen consumption (cerebral metabolic rate of oxygen-CMRO(2)) to CBF and CMR(glc). To test whether the mismatch reflects a specific role of aerobic glycolysis during functional brain activation, we determined CBF and CMRO(2) with positron emission tomography (PET) when 12 healthy volunteers executed finger-to-thumb apposition of the right hand. Movements began 1, 10, or 20 minutes before administration of the radiotracers. In primary and supplementary motor cortices and cerebellum, CBF had increased at 1 minute of exercise and remained elevated for the duration of the 20-minute session. In contrast, the CMRO(2) numerically had increased insignificantly in left M1 and supplementary motor area at 1 minute, but had declined significantly at 10 minutes, returning to baseline at 20 minutes. As measures of CMR(glc) are impossible during short-term activations, we used measurements of CBF as indices of CMR(glc). The decline of CMRO(2) at 10 minutes paralleled a calculated decrease of OGI at this time. The implied generation of lactate in the tissue suggested an important hypothetical role of the metabolite as regulator of CBF during activation. PMID- 22781334 TI - Albumin therapy enhances collateral perfusion after laser-induced middle cerebral artery branch occlusion: a laser speckle contrast flow study. AB - Laser speckle contrast (LSC) was used to compare the extent of cortical ischemia in two inbred mouse strains that differed in their degree of collateral circulation, after laser occlusion of the distal middle cerebral artery, and after treatment with 25% albumin (ALB) or saline (control). Sequential LSC images acquired over ~90 minutes were coaligned, converted to relative flow, and normalized to baseline. After 3-day survival, infarction was quantified by triphenyl tetrazolium chloride or magnetic resonance imaging. In the sparsely collateralized BALB/c strain, mean flow fell to 13% to 14% and 33% to 34% of baseline in central (core) and peripheral (penumbral) regions of interest, and ALB treatment at 30 minutes enhanced perfusion in both regions by ~2-fold relative to saline, restoring flow to the benign-oligemic range centrally, and to the hyperemic range peripherally. The ALB-induced increment in parenchymal perfusion was disproportionate to the subtle flow increase in the occluded artery itself, suggesting that ALB improved collateral circulation. Cortical infarction in BALB/c mice was reduced 45% by ALB treatment. In contrast to BALB/c mice, the better-collateralized CD-1 strain developed milder ischemia, had smaller infarcts, and showed no differential benefit of ALB. We conclude that where native collateralization is insufficient (BALB/c strain), ALB treatment exerts a significant therapeutic effect after ischemia by augmenting collateral perfusion. PMID- 22781335 TI - Cortical spreading depression shifts cell fate determination of progenitor cells in the adult cortex. AB - Cortical spreading depression (SD) is propagating neuronal and glial depolarization and is thought to underly the pathophysiology of migraine. We have reported that cortical SD facilitates the proliferative activity of NG2 containing progenitor cells (NG2 cells) that give rise to oligodendrocytes and immature neurons under the physiological conditions in the adult mammalian cortex. Astrocytes have an important role in the maintenance of neuronal functions and alleviate neuronal damage after intense neuronal excitation, including SD and seizures. We here investigated whether SD promotes astrocyte generation from NG2 cells following SD stimuli. Spreading depression was induced by epidural application of 1 mol/L KCl solution in adult rats. We investigated the cell fate of NG2 cells following SD-induced proliferation using 5' bromodeoxyuridine labeling and immunohistochemical analysis. Newly generated astrocytes were observed only in the SD-stimulated cortex, but not in the contralateral cortex or in normal cortex. The astrocytes were generated from proliferating NG2 cells. Astrogenesis depended on the number of SD stimuli, and was accompanied by suppression of oligodendrogenesis. These observations indicate that the cell fate of NG2 cells was shifted from oligodendrocytes to astrocytes depending on SD stimuli, suggesting activity-dependent tissue remodeling for maintenance of brain functions. PMID- 22781336 TI - Increased intracranial pressure after diffuse traumatic brain injury exacerbates neuronal somatic membrane poration but not axonal injury: evidence for primary intracranial pressure-induced neuronal perturbation. AB - Increased intracranial pressure (ICP) associated with traumatic brain injury (TBI) is linked to increased morbidity. Although our understanding of the pathobiology of TBI has expanded, questions remain regarding the specific neuronal somatic and axonal damaging consequences of elevated ICP, independent of its impact on cerebral perfusion pressure (CPP). To investigate this, Fischer rats were subjected to moderate TBI. Measurements of ICP revealed two distinct responses to injury. One population exhibited transient increases in ICP that returned to baseline levels acutely, while the other displayed persistent ICP elevation (>20 mm Hg). Utilizing these populations, the effect of elevated ICP on neuronal pathology associated with diffuse TBI was analyzed at 6 hours after TBI. No difference in axonal injury was observed, however, rats exhibiting persistently elevated ICP postinjury revealed a doubling of neurons with chronic membrane poration compared with rats exhibiting only transient increases in ICP. Elevated postinjury ICP was not associated with a concurrent increase in DNA damage; however, traditional histological assessments did reveal increased neuronal damage, potentially associated with redistribution of cathepsin-B from the lysosomal compartment into the cytosol. These findings indicate that persistently increased ICP, without deleterious alteration of CPP, exacerbates neuronal plasmalemmal perturbation that could precipitate persistent neuronal impairment and ultimate neuronal death. PMID- 22781337 TI - Effects of therapeutic hypothermia on inflammasome signaling after traumatic brain injury. AB - Traumatic brain injury (TBI) activates the NALP1/NLRP1 inflammasome, which is an important component of the early innate inflammatory response to injury. We investigated the influence of therapeutic hypothermia on inflammasome activation after TBI. Adult male Sprague-Dawley rats were subjected to moderate fluid percussion brain injury. Temperature manipulation (33 degrees C or 37 degrees C) was initiated 30 minutes after TBI and maintained for 4 hours. At 4 or 24 hours after TBI, traumatized cortex and hippocampus were prepared for immunoblot or immunohistochemical analysis. In the normothermic groups, caspase-1, caspase-11 and expression of the purinergic receptor P2X7 increased at 24 hours after TBI. Posttraumatic hypothermia lead to decreased expression of these proteins at 24 hours compared with normothermic levels. Immunocytochemical studies showed that posttraumatic hypothermia also decreased caspase-1 staining in cerebral cortical neurons compared with normothermic TBI. Cultured cortical neurons subjected to stretch injury demonstrated significant secretion of caspase-1 into the culture medium and caspase-3 activation, both results reduced by hypothermic treatment. Posttraumatic hypothermia decreases inflammasome signaling in neurons and reduces the innate immune response to TBI at 24 hours after injury. Therapeutic hypothermia may protect the injured central nervous system by targeting the detrimental consequences of the innate immune response to injury. PMID- 22781338 TI - Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats. AB - Many neuroprotective agents have been effective in experimental stroke, yet few have translated into clinical application. One reason for this may be failure to consider clinical comorbidities/risk factors in experimental models. We have shown that a naturally occurring interleukin-1 receptor antagonist (IL-1Ra) is protective against ischemic brain damage in healthy animals. However, protective effects of IL-1Ra have not been determined in comorbid animals. Thus, we tested whether IL-1Ra protects against brain injury induced by experimental ischemia in aged JCR-LA (corpulent) rats, which have clinically relevant risk factors. Male, aged, lean, and corpulent rats exposed to transient (90 minutes) occlusion of the middle cerebral artery (tMCAO) were administered two doses of IL-1Ra (25 mg/kg, subcutaneously) during reperfusion. Brain injury and neuroinflammatory changes were assessed 24 hours after tMCAO. Our results show that IL-1Ra administered at reperfusion significantly reduced infarct volume measured by magnetic resonance imaging (50%, primary outcome) and blood-brain barrier disruption in these comorbid animals. Interleukin-1Ra also reduced microglial activation, neutrophil infiltration, and cytokines levels in the brain. These data are the first to indicate that IL-1Ra protects against ischemic brain injury when administered via a clinically relevant route and time window in animals with multiple risk factors for stroke. PMID- 22781339 TI - Middle ear effusion in mechanically ventilated patients: effects of the nasogastric tube. AB - BACKGROUND: Middle ear effusion (MEE) is rare among adults, but has a higher incidence among ICU patients. The aim of this study was to analyze the effect of nasogastric tube (NGT) on MEE and to assess other predisposing factors. METHODS: Prospective observational study, carrying out an otoscopic examination and tympanometry in 100 mechanically ventilated patients. Immittance testing was carried out within 24 hours of ICU admission and every 72 hours until ICU discharge. In a case of persisting pathologic curve at the moment of discharge from ICU, there was a follow-up examination every 3 days until middle ear function was restored. In addition to descriptive variables, we recorded placement (left or right nostril) and diameter (12, 16, or 18 French) of the NGT. A Cox regression analysis was performed, adjusted for the days since ICU admission. RESULTS: A total of 535 tympanometry studies were carried out, of which 352 were normal and 183 observations presented MEE. We observed that 12 and 16 French NGTs were not significantly associated with abnormal middle ear function, whereas 18 French NGT was significantly associated with MEE (odds ratio 2.54, 95% CI 1.42-4.55; P = .01). Other variables independently associated with pathological tympanogram curves were Ramsay Sedation Scale score >= 4 (odds ratio 2.42, 95% CI 1.65-3.55; P = .01) and orotracheal intubation (odds ratio 5.72, 95% CI 3.40-9.60; P = .01). No intracranial infection or long-term disabilities were identified. CONCLUSIONS: MEEs and tympanometric alterations are frequent in intubated patients (32% in our study). To prevent these complications, they should receive NGTs with a diameter lower than 18 French, when feasible. PMID- 22781340 TI - Promoting optic nerve regeneration. AB - Vision is the most important sense for humans and it is irreversibly impaired by axonal damage of retinal ganglion cells (RGCs) in the optic nerve due to the lack of axonal regeneration. The failure of regeneration is partially attributable to factors located in the inhibitory environment of the forming glial scar and myelin as well as an insufficient intrinsic ability for axonal regrowth. Moreover, RGCs undergo apoptotic cell death after optic nerve injury, eliminating any chance for regeneration. In this review, we discuss the different aspects that cause regenerative failure in the optic nerve. Moreover, we describe discoveries of the last two decades demonstrating that under certain circumstances mature RGCs can be transformed into an active regenerative state allowing these neurons to survive axotomy and to regenerate axons in the injured optic nerve. In this context we focus on the role of the cytokines ciliary neutrophic factor (CNTF) and leukemia inhibitory factor (LIF), their receptors and the downstream signaling pathways. Furthermore, we discuss strategies to overcome inhibitory signaling induced by molecules associated with optic nerve myelin and the glial scar as well as the regenerative outcome after combinatorial treatments. These findings are encouraging and may open the possibility that clinically meaningful regeneration may become achievable one day in the future. PMID- 22781341 TI - Detection of equine infectious anaemia virus in native Japanese ponies. PMID- 22781342 TI - Intra and postoperative assessment of re-sterilised Ligasure Atlas for orchidectomies in horses: clinical study. AB - Horses (n=35) underwent orchidectomy in a single institution with a re-sterilised LSA as sole means of haemostasis. During the surgery, the gross quality of the seal, the stickiness of the forceps to the tissues, bleeding/oozing from the stump and the need for a subsequent application in already severed spermatic cord were assessed for haemostasis quality. After surgery, physical parameters (appearance of the mucous membranes, quality of the peripheral pulse, heart rate, respiratory rate, rectal temperature and blood dripping from the incisions), haematology or packed cell volume and total protein were monitored to assess signs of bleeding or any other condition. For cleanliness and asepsis assessment, signs of surgical infection were recorded. Complications during surgery were mild degree of sticking of the LSA forceps to the tissues and dulling of the blade. There was no need to reapply LSA a second time except in one horse. This means a haemostasis complication rate of 2.85 per cent of the horses. No postoperative bleeding was detected. Only two horses with fever had associated signs of surgical site infection. This means an infection rate of 5.71 per cent of the horses. PMID- 22781343 TI - Dynamics of bovine herpesvirus type 1 infection in Estonian dairy herds with and without a control programme. AB - Bovine herpesvirus type 1 (BHV-1) is an important bovine pathogen, exacerbating poor health and the productivity of cattle. The aims of this study were to detect the efficacy of vaccination programmes in lowering the seroprevalence of BHV-1 gE within the dairy herd and to follow the dynamics of the infection in non vaccinated herds with uninfected heifers. A two-year longitudinal study was carried out on seven herds that were vaccinated, and in five herds with uninfected heifers without applying a control programme. After the start of the vaccination programme, calves born remained free from the virus. However, in one herd, 7 per cent (95 per cent CI 2 to 18) of these animals showed antibodies to BHV-1 two years after the first vaccination. A decline in BHV-1 antibody prevalence was found in vaccinating herds. Among the five herds not under the control programme, one experienced active virus spread, although one herd experienced self-clearance of the virus. In the herds with high BHV-1 prevalence, vaccinating all cattle from three months of age twice a year with a commercial inactivated marker vaccine efficiently protected offspring from becoming infected, and lowered the prevalence of BHV-1 within the herd. A small proportion of herds may experience self-clearance of the virus. PMID- 22781344 TI - Preliminary investigation to establish prevalence and risk factors for being overweight in pet rabbits in Great Britain. PMID- 22781345 TI - First detection of 'Candidatus Mycoplasma haemolamae' infection in alpacas in England. AB - This is the first report of detection of Candidatus Mycoplasma haemolamae in alpacas in England. The primary case occurred in a three year-old male alpaca in the south-east of England which presented with a history of progressive weight loss, lethargy, swelling of the scrotum and pale mucous membranes. Blood smear examination revealed a moderate, regenerative anaemia, with numerous small basophilic coccoid structures consistent with Candidatus M haemolamae. To confirm the presence of Candidatus M haemolamae, a portion of the 16S rDNA gene was amplified and analysed by denaturing gradient gel electrophoresis (DGGE). 16S rDNA gene sequencing showed a 99.8 per cent homology with Candidatus M haemolamae sequences deposited in GenBank. Subsequently, a cross-sectional study was carried out to investigate the presence of Candidatus M haemolamae infection in the alpaca herd from which the primary case was detected (n=131). Blood smear examinations and PCR with DGGE were used and compared with a species-specific PCR. The prevalence of infection when PCR positive results were combined was 29 per cent. A substantial agreement between the PCR/DGGE and the species-specific PCR was found (kappa=0.86). A significant association was also found between age and infection (P=0.04) while no significant association was found with sex or origin. PMID- 22781346 TI - Surface-plasmon-based colorimetric detection of Cu(II) ions using label-free gold nanoparticles in aqueous thiosulfate systems. AB - We report colorimetric, label-free and non-aggregation-based gold nanoparticle (AuNP) probes for the highly selective detection of Cu(II) ions in aqueous environments. This detection scheme relies on the ability of Cu(II) ions to catalyze the leaching of gold at room temperature in the presence of thiosulfate species and ammonia. This simple and cost-effective probe provides rapid detection of Cu(II) ions at concentrations as low as 10 ppm. A similar detection method using AuNPs in ammonia-free thiosulfate solution is also viable at moderate reaction temperature (50 degrees C). The ammonia-free method also leads to marked damping and red-shifting of the surface plasmon resonance signal of the AuNP dispersion. The two methods clearly differ in the nature of the surface plasmon damping phenomenon, and their working mechanisms are plausibly explained based on the experimental investigations. PMID- 22781347 TI - [Development of the molecular classification study of glioblastoma in Chinese population]. PMID- 22781348 TI - [Feature analysis of IDH1 mutation in oligodendroglial tumors]. AB - OBJECTIVE: To analyze the features of isocitrate dehydrogenase 1 (IDH 1) mutation in 165 oligodendroglial tumors. METHODS: IDH1 was detected in a series of 165 oligodendroglial paraffin specimens from 2009 to 2011. And their features were analyzed. RESULTS: Mutant IDH1 was detected in 111 (67.3%) tumors including 109 (98.2%) CGT->CAT mutations, 1 (0.9%) CGT->AGT mutation and 1 (0.9%) CGT->TGT mutation. The frequencies of IDH mutation in AO, O and OA were 13/15, 83.3% and 72.9% respectively. They were significantly higher than that in AOA (27.0%, P < 0.001). CONCLUSION: The different frequencies of IDH1 mutation in different subsets of oligodendroglial tumors may imply varied tumorigenic pathways between subsets. PMID- 22781349 TI - [Role of Rac1 in the SDF-1-induced migration and invasion of human glioma cell line U251]. AB - OBJECTIVE: To explore the role of Rac1 in the SDF-1-induced migration and invasion of glioma cells with a specific Rac1 inhibitor. METHODS: Human glioma cell lines U251 treated with SDF-1 or/and specific Rac1 inhibitor were used. The migration and invasion capacities of cells in 2D cell migration/3D invasion assay were assessed. Western blot was employed to detect the levels of Rac1 and GAPDH in cell lysates and the Rac1 activity measured by Rac1 activation assays. Immunofluorescence was used to identify the expression and intracellular location of Rac1 in U251 cells. RESULTS: SDF-1 significantly increased the migration and invasion capacities of U251 cells (P < 0.05). The stimulation of SDF-1 boosted the activity of Rac1 versus the unstimulated cells (P < 0.05). And Rac1 was recruited to protruding edge in SDF-1-stimulated cells. Inhibition of Rac1 with specific Rac1 inhibitor decreased the migration and invasion capacities of SDF-1 induced U251 cells (P < 0.05). In comparison with the SDF-1 treated group, the activity of Rac1 significantly decreased (P < 0.05) and the recruitment of Rac1 to protruding edge significantly decreased in the NSC23766 pre-treated group. CONCLUSIONS: This study provides novel evidence that Rac1 modulates the SDF-1 induced migration and invasion of glioma cells. It suggests that the inhibition of Rac1 activation may be a new therapeutic target for glioma. PMID- 22781350 TI - [Targeted therapy of malignant glioma by a chimeric fusion toxin composed of IL 13 and Pseudomonas exotoxin in vitro]. AB - OBJECTIVE: To examine the antitumor activity of IL-13PE38 on solid malignant glioma cells in vitro and to investigate its relationship between the antitumor activity of IL-13PE38 and the expression level of IL-13Ralpha2 in malignant glioma. METHODS: Ten fresh tissues of anaplastic glioma and 11 fresh tissues of glioblastoma multiforme were obtained during craniotomy at First Affiliated Hospital, Wenzhou Medical College between June 2009 and December 2010. All fresh glioma cells were cultured in vitro with IL-13PE38. Then the cytotoxicity of IL 13PE38 was determined by colorimetric MTS proliferation assay and the SR (survival rate) calculated. The expression level of IL-13Ralpha2 was studied by immunohistochemical SABC method in 21 cases of malignant glioma. And the value of integrated optical density (IOD) was examined by computer assisted pathological image analysis system. The correlation between the IOD of IL-13Ralpha2 and the SR of malignant glioma cells was also studied. RESULTS: (1) There were strongly positive expression of IL-13Ralpha2 in most cases (19/21, 90%). And the expression level of IL-13Ralpha2 in glioblastoma multiforme was higher than the expression level of IL-13Ralpha2 in anaplastic glioma (P < 0.05). (2) As the fresh malignant glioma cells were cultured with IL-13PE38 of same concentration, the number of surviving cells decreased in different degrees. The survival rate of 14 cases were < 70% and 9 cases < 50%. And the survival rate of anaplastic glioma cells was higher than that of glioblastoma multiforme cells (P < 0.05). (3) The IOD of IL-13Ralpha2 and the SR of malignant glioma cells were strongly negatively correlated (r = -0.093, P < 0.01). CONCLUSION: A low concentration of IL-13PE38 shows a high level of cytotoxicity for solid malignant glioma cells. And its cytotoxic efficiency depends on the expression level of IL-13Ralpha2. PMID- 22781351 TI - [Effect and prognostic analysis of radiofrequency ablation in treating advanced hepatocellular carcinoma]. AB - OBJECTIVE: To evaluate the effect of ultrasound-guided percutaneous radiofrequency ablation (RFA) in treating advanced hepatocellular carcinoma (HCC) and to analyze the prognostic factors. METHODS: A total of 90 patients with unresectable advanced HCC underwent percutaneous RFA therapy between July 2000 and June 2011 were enrolled into the study. According to the 6th UICC/AJCC-TNM system, 80 and 10 patients were in stage III and IV, respectively.78 patients were men and 12 patients were women. Ages ranged from 24 to 87 years old (mean +/ SD, 59 +/- 12 years). The tumor size ranged from 1.5 to 8.0 cm (mean +/- SD, 4.5 +/- 1.4 cm). The maximum tumor of 73 patients (81.1%) was larger than 3.0 cm. 31 patients (34.4%) had 2-4 tumors. The Child-Pugh classification of B and C were 32 patients (35.6%) altogether. By regular follow-up, enhanced CT combined with AFP was used to evaluate the effect after RFA. Kaplan-Meier model and Log-rank test were used in univariate analysis and Cox regression model was used in multivariate analysis to identify prognostic factors for survival. P < 0.05 was considered statistically significant difference. RESULTS: Complete tumor necrosis rate after initial RFA was 90.9% (120/132 tumors). Serious complications were developed in two patients (2.2%) and no treatment-related death occurred. 3 - 129 months were followed up. Local recurrence rate was 15.2% (20/132 tumors). The 1-, 3-, 5-year overall survival rates were 83.3%, 48.3%, 21.9%, respectively, and the median survival time was 35 months. The univariate analyses showed that patients with Child-Pugh classification of A, tumor less than 3.0 cm, applying CEUS, using standard treatment protocols, achieving complete tumor necrosis and without tumor recurrence survived longer (P < 0.05). Child-Pugh classification and the standard treatment protocols were identified as independent prognostic factors for survival by multivariate model (P = 0.001, P < 0.001). CONCLUSION: Paying attention to the following factors of CEUS, standard treatment protocols, initially complete tumor necrosis and liver protection therapy for patients with advanced HCC is helpful to improve the patients' survival. PMID- 22781352 TI - [The impact of antiviral therapy on virus-specific T-cell reactivity in patients with chronic hepatitis B]. AB - OBJECTIVE: To investigated the impact of viral load decline on virus-specific T cell reactivity on patients with chronic hepatitis B. METHODS: 23 cases of patients with chronic hepatitis B were recruited randomized to therapy with nucleoside analogue or alpha interferon from January 2009 to April 2010. Peripheral blood mononuclear cells (PBMCs) were collected longitudinally at baseline and the time of HBV DNA undetected. T-cell reactivity to HBV core antigens were tested using Elispot assays and Luminex. RESULTS: (1) The frequency of T cell reactivity induced by HBcAg in patients with chronic hepatitis B were 91.3% at the time of HBV DNA undetected, which significantly higher than The frequency of 69.6% at baseline. The frequency between nucleoside analogue treatment group and alpha interferon treatment group was no significant difference. (2) The average response magnitude was expressed as spot forming unit (SFU) per million input cells. SFU of T cell responses to HBcAg was 120 SFU/10(6) PBMCs at baseline, much lower than SFU of 1060 SFU/10(6) PBMCs at the time of HBV DNA undetected. No significant difference between patients with negative T cell reactivity at baseline and patients with positive T cell reactivity at baseline was found. In patients with initial virological response (IVR) to therapy and patients with early virological response (EVR), no significant difference was found in the magnitude at baseline as well as at the time of HBV DNA undetected. (3) The average response magnitude of nucleoside analogue treatment group was 1713 SFU/10(6) PBMCs at the time the time of HBV DNA undetected, higher than 189 SFU/10(6) PBMCs at baseline. But in interferon treatment group, the average response magnitude was no significant difference, 120 SFU/10(6) PBMCs at the baseline and 305 SFU/10(6) PBMCs at the time the time of HBV DNA undetected respectively. The average response magnitude in nucleoside analogue treatment group was greater than that in interferon treatment group. (4) As to compare difference of IFN-gamma concentration in supernatant of T cell culture solution stimulated by HBcAg, IFN-gamma secreted by T cell at the time of HBV DNA undetected was clearly higher than IFN-gamma secreted at baseline, (38 +/- 9) ng/L and (90 +/- 9) ng/L respectively. CONCLUSIONS: Antiviral therapy made profit to improve virus-specific T-cell reactivity in patients with chronic hepatitis B, suggesting the importance to investigate HBV specific T cell responses. PMID- 22781353 TI - [Survey of blindness and low vision among residents in Shuimogou District, Urumqi, China in 2010]. AB - OBJECTIVE: To estimate the prevalence of visual impairment among adults aged >= 40 years, compare the prevalence between Uyghur and Han residents and analyze the causes of visual impairment. METHODS: Population-based cluster sampling survey was conducted among a target population of 5032 persons >= 40 years of age from Shuimogou District in Urumqi, Xinjiang Uyghur Autonomous Region. Distance visual acuity (VA) was measured with a Tumbling-E chart at 5 m. Presenting and best corrected VA were recorded. Clinical evaluations were performed. And primary causes of visual impairment was determined for those with VA < 0.3. RESULTS: Among them, there were 4104 responders (Uyghur 2006 persons, Han 2098 persons) with a response rate 81.56%. Prevalence of bilateral blindness was 1.25%/1.86% (Uyghur/Han) (P < 0.05) and bilateral low vision 4.04%/3.29% (Uyghur/Han) (P < 0.05). Primary cause of visual impairment among participants was cataract (cause proportion of 49.23% among Uyghurs and 51.85% among Hans). Visual impairment was correlated with advanced age, males and poor literacy. Prevalences of bilateral blindness and bilateral low vision in age group 40 - 50 yr increased from 0.48% and 1.13% to 3.47% and 10.88% in age group >= 70 among Uygur citizens respectively (chi(2) = 22.36, P < 0.05 vs chi(2) = 70.97, P < 0.05). Relative data among the Han citizens varied from 0% and 1.42% to 4.39% and 7.89% (chi(2) = 27.94, P < 0.05 vs chi(2) = 39.99, P < 0.05). CONCLUSION: The most frequent cause of visual impairment in this area is cataract (Uyghur 49.23% vs Han 51.85%) while retinal diseases and glaucoma are important causes as well. Blindness prevention programs targeting the elderly should be expanded, particularly in areas with a limited access and affordability of eye care services. PMID- 22781354 TI - [Endovascular treatment for venous sinus stenosis in idiopathic intracranial hypertension]. AB - OBJECTIVE: To explore the relationship of venous sinus stenosis and idiopathic intracranial hypertension (IIH) and to discuss the efficacy and strategy of endovascular treatment. METHODS: Balloon angioplasty and stent placement were performed in 24 IIH cases by lateral sinus stenosis. Mechanical thrombus maceration was performed before stent placing in 5 cases with suspected chronic dural sinus thrombosis. The clinical data of clinical presentations, intracranial pressure, pressure of lateral sinus, pressure gradient between distal and proximal lateral sinus stenosis, methods of treatment and therapeutic outcomes were retrospectively analyzed. RESULTS: Intracranial pressure dropped from (314 +/- 56) mm H2O of pre-operation to (197 +/- 31) mm H2O of post-operation. The post-treatment pressure gradient was obviously high ((159 +/- 11) mm H2O) and a reduction was found ((95 +/- 11) mm H2O). Headache in 16 cases, vision in 13 and papilledema in 10 were resolved or improved. There was no other permanent procedure-related morbidity. The patients were followed up for 2 - 19 months. And no in-stent restenosis occurred. CONCLUSION: Endovascular treatment is effective for IIH by venous sinus stenosis. PMID- 22781355 TI - [Bloodless medical and surgical procedures for retroperitoneal neoplasm resection]. AB - OBJECTIVE: To investigate the Bloodless Medical and Surgical Procedures for retroperitoneal neoplasm resection. METHODS: Retrospectively analyse the Bloodless Medical and Surgical Procedures during 36 retroperitoneal neoplasm resections from Beijing Shijitan Hospital Affiliated to Capital Medical University from September 2009 to December 2010, to discuss the preoperative preparation, anesthetic induction and maintainance, intraoperative monitoring and use of vasoactive drugs related experience. RESULTS: All the patients were safe during the perioperative period, without any operative and anesthetic complication. By applying the Bloodless Medical and Surgical Procedures, the intraoperative haemodynamics maintained steady, the mean hematocrit decreased from 0.368 +/- 0.095 before autologous blood collection to 0.252 +/- 0.032 before the ends of operation. Majority of the patients (91.7%) stop using vasoactive drugs and extubated within 1 h after operation, and return wards. CONCLUSION: Erythrocyte-raising medicine therapy and modified preservation autologous blood transfusion are important process of Bloodless Medical and Surgical Procedures. PMID- 22781356 TI - [Comparison of two techniques in hemivertebra resection: anterior- posterior approach versus posterior approach]. AB - OBJECTIVE: To Compare the two techniques in the treatment of congenital kypho scoliosis caused by fully-segmented hemivertebra. METHODS: 44 consecutive cases, 21 males and 23 females. The average age at surgery was 11.4 years ranging from 2 to 17 years, 20 patients underwent one-stage anterior and posterior hemivertebra resection and instrumentation. 24 patients underwent one-stage posterior hemivertebra resection and instrumentation. Long cassette standing radiographs were taken before and after surgery and at the final follow-up. The apical translation, the Cobb's angle in the coronal and sagittal plane were measured and analyzed. The medical records were reviewed and the complications were recorded. RESULTS: The average follow-up was 39.2 months ranging from 24 to 72 months. The 2 groups did not demonstrate any significant differences in gender, age at surgery, preoperative and postoperative Cobb angle, blood loss, or fusion segments (all P > 0.05). However, the anterior and posterior group demonstrated a less curve flexibility and longer operative time compared with the posterior groups (all P < 0.05). COMPLICATIONS: the anterior and posterior group included pedical cutting in 1 case, lumber curve decompensation in 1 case and crankshaft phenomenon in 2 cases. The posterior group included pedical cutting in 1 case and length of instrumentation in 1 case. CONCLUSIONS: Two techniques are safe and effective procedure for the congenital kypho-scoliosis. Anterior and posterior hemivertebra resection is indicated to rigid deformity, and anterior epiphysiodesis is needed to avoid crankshaft phenomenon for patients at an earlier skeletal age. Posterior hemivertebra resection can save operation time and is less invasive compared with anterior-posterior approach. PMID- 22781357 TI - [Application of C1-C2 pedicle screw fixation in atlantoaxial complex fracture]. AB - OBJECTIVE: To explore the therapeutic effects of posterior transpedicular screw internal fixation in atlantoaxial complex fracture patients. METHODS: Among 17 patients, there were Anderson II type of odontoid plus atlas fracture (n = 10) and Hangman plus atlas fracture (n = 7). They were categorized by their preoperative spinal cord scores according to the Frankel classification: C-class (n = 2), D-class (n = 6) and E-class (n = 5). Transpedicular screw internal fixation was performed to stabilize atlas and axis in 8 cases. Granular allograft bone was planted onto the surface of posterior arches in both atlas and axis. And the other 5 cases underwent no bony fusion. RESULTS: All patients were followed up for an average of 24 months. All screws were successfully placed in atlas and axis. And the cases of atlantoaxial dislocation were reduced. Bony fusion was observed at Months 3 - 6 post-operation. Atlantoaxial rotational function restored satisfactorily in all patients. But axial rotation was partially lost. CONCLUSION: Posterior transpedicular screw internal fixation can regain atlantoaxial joint stability immediately and promote bony fusion. And it is an effective therapy for atlantoaxial complex fracture. PMID- 22781358 TI - [Evaluation of arterial elasticity in initial hypertension by pulse wave velocity and wave intensity technique]. AB - OBJECTIVE: To explore the early changes of arterial elasticity in initial hypertension through two different methods. METHODS: A total of 76 hypertensive patients (Grade 1-2, n = 32) were assigned into hypertension group while the age and gender-matched healthy population was selected as normal group (n = 44). All of them were monitored for baPWV in right carotid artery by wave intensity technique. The parameters of two methods were compared between two groups. RESULTS: Higher bi-lateral baPWV were found in the hypertension group (right: (1472 +/- 198) m/s vs (1353 +/- 233) m/s), (left: (1465 +/- 198) m/s vs (1353 +/- 241) m/s) (P < 0.05). Compared with the normal group, Patients in the hypertension group had statistically higher W(1) ((9.8 +/- 3.8)*10(3) mm Hg*m*s( 3) vs (7.4 +/- 2.4)*10(3)) mm Hg*m*s(-3), W(2) ((2.8 +/- 1.1)*10(3) mm Hg*m*s(-3) vs (2.0 +/- 1.0)*10(3) mm Hg*m*s(-3)), stiffness parameter (beta) ((6.9 +/- 2.6) vs (5.1 +/- 1.3)), pressure-strain elastic modulus (Ep) ((99 +/- 39) kPa vs (57 +/- 17) kPa), one-point wave velocity (PWVbeta) ((6.0 +/- 1.1) m/s vs (4.6 +/- 0.6) m/s), PWVWI ((6.2 +/- 1.4) m/s vs (4.4 +/- 1.0) m/s) (P < 0.01). R-W(1) ((100 +/- 14) ms vs (103 +/- 13) ms), (W(1)-W(2)) ((261 +/- 20) ms vs (274 +/- 15) ms) and arterial compliance (AC) ((0.8 +/- 0.4) mm(2)/kPa vs (1.1 +/- 0.3) mm(2)/kPa) in the hypertension group were statistically lower than those of the normal group (P < 0.05). CONCLUSION: The initial hypertensive patients may have impaired arterial elasticity during an early stage. PMID- 22781359 TI - [PreC/C gene-targeting RNA interference suppresses hepatitis B virus replication and expression in human hepatoma cells]. AB - OBJECTIVE: To explore the antiviral efficacy of small interfering RNAs (siRNAs)/shRNA targeting preC/C of HBV in human hepatoma cells Huh-7 and HepG2.2.15 cells. METHODS: Three 21 nucleotide(nt) siRNAs for treating HBV preC/C gene were designed and synthesized according to the HBV genome in GenBank accession numbers (U95551); simultaneously, one 21-nt-long non-homologous siRNA was also designed randomly for negative control. They were cloned into vector pU6 for constructing shRNA-expressing plasmids pU6-C1, pU6-C2, pU6-C3 and control pU6 C4. To assess the function of siRNAs, a reporter gene system was constructed. The HBV preC/C gene was synthesized by PCR with pT-HBV1.3 as the template. The preC/C gene was then inserted into the enhanced green fluorescent protein expression vector (EGFP-N1) in order to construct the recombinant plasmid pEGFP-preC/C (E C), which carries the EGFP reporter gene. The three shRNA-expressing plasmids-pU6 C1, pU6-C2, or pU6-C3-was each then cotransfected into Huh-7 cells along with either reporter gene expression vector E-C or the controls; or these three plasmids-pU6-C1, pU6-C2, or pU6-C3-was each cotransfected into HepG2.2.15 cells along with the controls. First, upon determination of the number of cells exhibiting EGFP expression in Huh-7cells as detected by an BH-2 fluorescence microscope and FACS-440 flow cytometry at different times after cotransfection, the investigators evaluated the inhibitory efficiency of the three shRNA expressing plasmids by an EGFP reporter system in cultured cells. Subsequently, the expression amount of HBsAg and HBeAg in HepG2.2.15 cell supernatant at 24, 48, 72 and 96 h post-cotransfection was detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to detect the expression of HBsAg and HBcAg at 72 h post-cotransfection in HepG2.2.15 cells. The copy level of HBV mRNA transcripts cDNA in HepG2.2.15 cells was further investigated through quantitative real-time polymerase chain reaction (real-time PCR). RESULTS: In comparison with single plasmid transfection pEGFP-N1 or E-C, fluorescence microscope examination and flow cytometry detection at 48 hours after cotransfection indicated that the expression of the reporter gene EGFP in cotransfected group Huh-7 cell involving pU6-C1, pU6-C2 or pU6-C3 resulted in an 80% reduction in EGFP signal relative to the controls (P < 0.01). It was also found through immunofluorescence that the expression of HBsAg and HBcAg in HepG2.2.15 cells was reduced markedly (P < 0.01), that the copy level of HBV mRNA transcripts cDNA as detected at 48 hours after cotransfection by quantitative real-time PCR was reduced respectively by 73.9% +/- 1.2% (P = 0.029), 48.2% +/- 1.8% and 35.8% +/- 1.4% (P = 0.037, 0.040) relative to the control, that it conformed with that detected by fluorescence microscope/flow cytometry, ELISA, and immunofluorescence (P < 0.01). Thereby further corroborating the antiviral efficacy of RNAi. The efficacy was obvious at 48 h, reaching a peak at 72 h. CONCLUSION: For the first time it has been found that RNAi induced by siRNA/shRNA targeting HBV preC/C gene is effective and specific in inhibiting HBV replication and expression in human hepatoma cells Huh-7 and HepG2.2.15 cells. Our data suggest that RNAi may provide an effective, viable approach in gene therapy to treating major infectious diseases such as HBV/HCV/HIV infection. PMID- 22781360 TI - [Role of toll like receptor 4 in low shear stress-induced intimal hyperplasia]. AB - OBJECTIVE: To determine the role of toll like receptor 4 (TLR4) in intimal hyperplasia induced by low shear stress (LSS). METHODS: TLR4(-/-) mice and control mice C57BL/6J were used. Polyethylene cuff was placed on murine carotid to establishing a LSS model. Cultured vascular endothelial cells under LSS condition were used as an in vitro LSS cell model. Intimal hyperplasia was evaluated pathologically. TLR4 was tested by Western blot and the expression of IL-1beta, IL-6 and TNF-alpha mRNA were detected using RT-PCR. Cell proliferation was determined by detecting DNA synthesis. RESULTS: LSS elicited significant carotid intimal hyperplasia in normal mice but a slight neointima formation in TLR4(-/-) mice (42.67 +/- 16.46 vs 7.03 +/- 2.95, P < 0.05). LSS upregulated the expression of TLR4 (2.30 +/- 0.66 vs 0.16 +/- 0.10, P < 0.05), as well as the mRNA of IL-1beta (6.52 +/- 3.15 vs 1.65 +/- 0.45, P < 0.01), IL-6 (16.17 +/- 7.49 vs 6.50 +/- 1.84, P < 0.01) and TNF-alpha(9.98 +/- 3.77 vs 2.72 +/- 1.03, P < 0.01) in normal mice. However, only moderate increases in IL-6 and TNF-alpha mRNA were observed in TLR4(-/-) mice. LSS induced the proliferation in cultured endothelial cells. And it was further enhanced by TLR4 overexpression (177 +/- 33 vs 83 +/- 15, P < 0.05) but attenuated by TLR4 silencing (40 +/- 8 vs 83 +/- 15, P < 0.05). CONCLUSION: TLR4 plays an important role in LSS-induced intimal hyperplasia. It is likely that LSS induces the proliferation of endothelial cells through TLR4-mediated inflammatory reaction and ultimately promotes intimal hyperplasia. PMID- 22781361 TI - [Detection of microvasculature in rat hind limb using synchrotron radiation]. AB - OBJECTIVE: To detect deep-level microvascular structure in rat hind limb by synchrotron radiation and microangiographic technique. METHODS: Microangiography in vivo and ex vivo was performed by synchrotron radiation based absorption imaging and phase contrast imaging, with omnipaque and barium sulfate solution as contrast media, respectively, and synchrotron radiation-based micro-computed tomography (SRmCT) was also performed to reveal three-dimensional morphology of the blood vessel in rat hind limb. RESULTS: Using microangiographic technique in vivo and in vitro (with barium sulfate), blood vessels in the rat limb muscle could be visualized with high resolution, and the fourth branches of iliac artery in rat hind limb could be detected with the minimum visualized blood vessels about 40 um and 9 um in diameter, respectively. In addition, the vascular network could be defined and analyzed at the micrometer scale from the 3D renderings of limb vessel as shown by SRmCT. CONCLUSION: Synchrotron radiation-based microangiography and SRmCT thus provided a practical and effective means to observe the microvasculature of rat hindlimb, which might be useful in assessment of angiogenesis in lower limbs. PMID- 22781362 TI - Sibling comparison designs: bias from non-shared confounders and measurement error. AB - Twins, full siblings, and half-siblings are increasingly used as comparison groups in matched cohort and matched case-control studies. The "within-pair" estimates acquired through these comparisons are free from confounding from all factors that are shared by the siblings. This has made sibling comparisons popular in studying associations thought likely to suffer confounding from socioeconomic or genetic factors. Despite the wide application of these designs in epidemiology, they have received little scrutiny from a statistical or methodological standpoint. In this paper we show, analytically and through a series of simulations, that the standard interpretation of the models is subject to several limitations that are rarely acknowledged.Although within-pair estimates will not be confounded by factors shared by the siblings, such estimates are more severely biased by non-shared confounders than the unpaired estimate. If siblings are less similar with regard to confounders than to the exposure under study, the within-pair estimate will always be more biased than the ordinary unpaired estimate. Attenuation of associations due to random measurement error in exposure will also be higher in the within-pair estimate, leading within-pair associations to be weaker than corresponding unpaired associations, even in the absence of confounding. Implications for the interpretation of sibling comparison results are discussed. PMID- 22781363 TI - 18F-FDG PET-CT during chemo-radiotherapy in patients with non-small cell lung cancer: the early metabolic response correlates with the delivered radiation dose. AB - BACKGROUND: To evaluate the metabolic changes on 18F-fluoro-2-deoxyglucose positron emission tomography integrated with computed tomography (18 F-FDG PET CT) performed before, during and after concurrent chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC); to correlate the metabolic response with the delivered radiation dose and with the clinical outcome. METHODS: Twenty-five NSCLC patients candidates for concurrent chemo radiotherapy underwent 18F-FDG PET-CT before treatment (pre-RT PET-CT), during the third week (during-RT PET-CT) of chemo-radiotherapy, and 4 weeks from the end of chemo-radiotherapy (post-RT PET-CT). The parameters evaluated were: the maximum standardized uptake value (SUVmax) of the primary tumor, the SUVmax of the lymph nodes, and the Metabolic Tumor Volume (MTV). RESULTS: SUVmax of the tumor and MTV significantly (p=0.0001, p=0.002, respectively) decreased earlier during the third week of chemo-radiotherapy, with a further reduction 4 weeks from the end of treatment (p<0.0000, p<0.0002, respectively). SUVmax of lymph nodes showed a trend towards a reduction during chemo-radiotherapy (p=0.06) and decreased significantly (p=0.0006) at the end of treatment. There was a significant correlation (r=0.53, p=0.001) between SUVmax of the tumor measured at during-RT PET-CT and the total dose of radiotherapy reached at the moment of the scan. Disease progression free survival was significantly (p=0.01) longer in patients with complete metabolic response measured at post-RT PET-CT. CONCLUSIONS: In patients with locally advanced NSCLC, 18F-FDG PET-CT performed during and after treatment allows early metabolic modifications to be detected, and for this SUVmax is the more sensitive parameter. Further studies are needed to investigate the correlation between the metabolic modifications during therapy and the clinical outcome in order to optimize the therapeutic strategy. Since the metabolic activity during chemo-radiotherapy correlates with the cumulative dose of fractionated radiotherapy delivered at the moment of the scan, special attention should be paid to methodological aspects, such as the radiation dose reached at the time of PET. PMID- 22781364 TI - Steroidogenesis in the adrenal dysfunction of critical illness: impact of etomidate. AB - INTRODUCTION: This study was aimed at characterizing basal and adrenocorticotropic hormone (ACTH)-induced steroidogenesis in sepsis and nonsepsis patients with a suspicion of critical illness-related corticosteroid insufficiency (CIRCI), taking the use of etomidate-inhibiting 11beta-hydroxylase into account. METHOD: This was a prospective study in a mixed surgical/medical intensive care unit (ICU) of a university hospital. The patients were 62 critically ill patients with a clinical suspicion of CIRCI. The patients underwent a 250-MUg ACTH test (n = 67). ACTH, adrenal steroids, substrates, and precursors (modified tandem mass spectrometry) also were measured. Clinical characteristics including use of etomidate to facilitate intubation (n = 14 within 72 hours of ACTH testing) were recorded. RESULTS: At the time of ACTH testing, patients had septic (n = 43) or nonseptic critical illness (n = 24). Baseline cortisol directly related to sepsis and endogenous ACTH, independent of etomidate use. Etomidate was associated with a lower baseline cortisol and cortisol/11beta-deoxycortisol ratio as well as higher 11beta-deoxycortisol, reflecting greater 11beta-hydroxylase inhibition in nonsepsis than in sepsis. Cortisol increases < 250 mM in exogenous ACTH were associated with relatively low baseline (HDL-) cholesterol, and high endogenous ACTH with low cortisol/ACTH ratio, independent of etomidate. Although cortisol increases with exogenous ACTH, levels were lower in sepsis than in nonsepsis patients, and etomidate was associated with diminished increases in cortisol with exogenous ACTH, so that its use increased, albeit nonsignificantly, low cortisol increases to exogenous ACTH from 38% to 57%, in both conditions. CONCLUSIONS: A single dose of etomidate may attenuate stimulated more than basal cortisol synthesis. However, it may only partly contribute, particularly in the stressed sepsis patient, to the adrenal dysfunction of CIRCI, in addition to substrate deficiency. PMID- 22781365 TI - Vector-borne pathogen spread through ticks on migratory birds: a probabilistic spatial risk model for South-Western europe. AB - Tick-borne pathogens can spread easily through the movements of infested birds. An important example is viruses that pose a threat to humans and that are carried in Hyalomma ticks that move from Africa into south-western Europe. This study evaluates the probability of arrival of migrating birds from Africa into Spain and the environmental suitability of different regions of Spain for the survival of tick stages introduced by these birds. This evaluation produced a spatial risk index measuring the probability that foreign tick populations will survive in the target area. Periods of highest risk were observed for large areas of Spain, from the second fortnight of April to the second fortnight of May. Although birds may arrive as early as January and massive migrations may take place in March, the environmental suitability for Hyalomma marginatum ticks is low in these periods and high mortality of the spread stages (nymphs) is expected. This study introduces new methods of objective analysis based on spatial and process-driven models for both ticks and hosts and critically evaluates the usefulness of spatial spreading methods for assessing the risk of tick-borne pathogens. PMID- 22781366 TI - Composition and antimicrobial activity of fatty acids detected in the hygroscopic secretion collected from the secretory setae of larvae of the biting midge Forcipomyia nigra (Diptera: Ceratopogonidae). AB - The hygroscopic secretion produced by the secretory setae of terrestrial larvae of the biting midge Forcipomyia nigra (Winnertz) was analysed using gas chromatography coupled with mass spectrometry (GC-MS). The viscous secretion is stored at the top of each seta and absorbs water from moist air. GC-MS analyses (four independent tests) showed that the secretion contained 12 free fatty acids, the most abundant of which were oleic (18:1), palmitic (16:0), palmitoleic (16:1) and linoleic (18:2). Other acids identified were valeric (5:0), enanthic (7:0), caprylic (8:0), pelargonic (9:0), capric (10:0), lauric (12:0), myristic (14:0) and stearic (18:0). Two other compounds, glycerol and pyroglutamic acid, were also found. The antibacterial activity of the fatty acids and pyroglutamic acid was tested using the agar disc diffusion method and targeted Gram positive (Bacillus cereus, Bacillus subtilis, Enterococcus faecalis) and Gram negative bacterial strains (Citrobacter freundii, Pseudomonas aeruginosa, Pseudomonas fluorescens). The antifungal activity was tested by determining minimal inhibitory concentration (MIC) of examined compounds. Fatty acids were tested against enthomopathogenic fungi (Paecilomyces lilacinus, Paecilomyces fumosoroseus, Lecanicillium lecanii, Metarhizium anisopliae, Beauveria bassiana (Tve-N39), Beauveria bassiana (Dv-1/07)). The most effective acids against bacterial and fungal growth were C(9:0), C(10:0) and C(16:1), whereas C(14:0), C(16:0,) C(18:0) and C(18:1) demonstrated rather poor antifungal activity and did not inhibit the growth of bacteria. The antimicrobial assay investigated mixtures of fatty and pyroglutamic acids (corresponding to the results of each GC-MS test): they were found to be active against almost all the bacteria except P. fluorescens and also demonstrated certain fungistatic activity against enthomopathogenic fungi. The hygroscopic secretion facilitates cuticular respiration and plays an important role in the antimicrobial protection of F. nigra larvae living in moist terrestrial habitats. PMID- 22781367 TI - Uptake and incorporation of sialic acid by the tick Ixodes ricinus. AB - We describe the detection of sialylated N-linked glycans in partially fed Ixodes ricinus tick females using matrix-assisted laser desorption/ionization time-of flight/time-of-flight mass spectrometry. Sialylated glycans were detected in salivary glands as well as in tick guts and we propose the host origin of these structures. In addition, we mapped the transport of sialylated structures from the blood meal through the gut to the salivary glands using electron microscopy. Specific localization of sialylated glycans to basement membranes of salivary glands was observed. Finally, the influence of the sample preparation methods for electron microscopy on ultrastructure and immunogold labeling was evaluated. PMID- 22781368 TI - Poly(ionic liquid)-wrapped single-walled carbon nanotubes for sub-ppb detection of CO2. AB - An ultrasensitive CO(2) sensor with a detection limit of 500 ppt was achieved using poly(ionic liquid)-wrapped single-walled carbon nanotubes as sensing materials. The sensor exhibited superior selectivity to CO(2) and was resistant to the interference of relative humidity. PMID- 22781369 TI - Could Chinese herbal medicine be nephrotoxic? PMID- 22781370 TI - In denial: misperceptions of weight change among adults in the United States. AB - OBJECTIVE: Obesity is associated with several chronic conditions, increased medical costs, and premature death. Proper assessment of changes in body weight is crucial to control the spread of obesity. We used data from the Behavioral Risk Factor Surveillance System to explore how adults in the United States recall their weight change and to identify characteristics associated with weight changes. METHODS: Data from two cross-sections of adults aged >=18 years from the 2008 (n=385,416) and 2009 (n=394,700) Behavioral Risk Factor Surveillance System were analyzed. Body mass index was calculated from self-reported height and weight. Self-reported estimates of weight 1 year prior to the interview were used to calculate changes in weight and obesity status between 2008 and 2009. RESULTS: If self-reported changes in weight between 2008 and 2009 are to be believed, the obesity prevalence among men and women in the United States would have declined by 2.0% and 0.9% respectively. Yet, obesity prevalence increased 0.4%, overall, during this tim'e period. In general, American adults overestimated their previous weight and reported weight losses even though they had gained weight. CONCLUSION: Public health and medical professionals should interpret self reported weight changes with caution when developing, implementing, and evaluating programs to control and prevent weight gain. PMID- 22781371 TI - Objects in the mirror: on the difference between denial and perceptual distortion in public health surveillance. PMID- 22781372 TI - Commentary on "Development of a prediction model for 10-year risk of hepatocellular carcinoma: the Japan Public Health Center-based Prospective Study Cohort II" by Michikawa et al. PMID- 22781373 TI - [The Saturn study]. PMID- 22781375 TI - [Statins and the "Cabala": the new Note 13]. AB - The new Note 13 introduces significant changes in the regulation of statin reimbursement. Although cardiovascular risk assessment still plays a key role, cardiovascular risk estimation has shifted from the "risk charts" to the more simple "sum of risk factors". In addition, the new Note 13 expands drug reimbursement to subjects at intermediate risk, who represent the main source of cardiovascular events because of the size of the population. As a consequence, the general trend of the new Note 13 is to simplify the rules that govern statin reimbursement and to guarantee treatment for all subjects at increased risk of cardiac and vascular events. PMID- 22781374 TI - [Patent foramen ovale and cardiovascular stroke: the eternal dilemma]. AB - Ischemic stroke is one of the leading causes of mortality and the most important determinant of disability in developed countries. Its association with patent foramen ovale is one of the more controversial issues of the literature, also because paradoxical embolism is frequently a diagnosis of suspicion. Up to now, no clinical randomized studies unequivocally demonstrated the causality of this association. Comparing international guidelines there are substantial differences in clinical recommendations among scientific societies, which confirm the uncertainty surrounding this field. Actually, the superiority of transcatheter percutaneous closure over medical therapy alone is not confirmed, partially as a consequence of significant variability in the inclusion criteria, technical approach, peri- and post-procedural therapy among different studies. Moreover, the procedure is very recent and very few studies report prospective data about the safety and effectiveness of patent foramen ovale closure at long-term follow up. A careful assessment of both clinical characteristics of patients and anatomical features of patent foramen ovale is very helpful to drive a personalized choice for the individual patient. On the basis of the available evidence, this review re-examines the impact of patent foramen ovale in the etiology of cryptogenic cerebrovascular events as well as the advantages and disadvantages of different treatment modalities, waiting for more scientific consensus. PMID- 22781376 TI - [Aspirin in primary prevention of cardiovascular diseases: how to balance risks and benefits]. AB - While the use of aspirin in the secondary prevention of cardiovascular atherothrombotic disease is well established, many aspects of primary prevention are still unclear. Uncertainties mostly depend on a doubtful risk-benefit ratio, because of the low atherothrombotic risk of populations involved on the one hand, and the non-negligible bleeding risk of treatment on the other. Areas of specific doubt are those of diabetes and asymptomatic peripheral arterial disease, where neither single trials nor meta-analyses allow issuing high-grade specific recommendations at the moment. The present review aims at giving an account on this topic, highlighting areas for further studies, but also attempting at providing a rationale for what to do practically now, while awaiting more conclusive evidence. Based on the results of a number of clinical trials and meta analyses, and especially considering the absolute figures of the benefit (major cardiovascular events avoided) and of the harm (major bleeding events occurred related to aspirin), the authors recommend to limit primary cardiovascular prevention with aspirin (in apparently healthy subjects with no previous cardiovascular events) to subjects with an estimated global cardiovascular risk >=2 major cardiovascular events per 100 patients-year, as assessed by the risk score assessments proposed in the Italian "Progetto Cuore" (www.progettocuore.it). This cut-off should also be adopted for primary prevention in patients with type 2 diabetes and/or asymptomatic peripheral arterial disease. PMID- 22781377 TI - [Polytherapy in cardiovascular prevention: open issues]. AB - Despite the considerable advances in preventive treatment achieved over the last two decades, the increasing burden of cardiovascular disease represents an urgent need for new therapeutic strategies to reduce cardiovascular mortality and morbidity. The current pandemic of obesity, hypertension and diabetes, as a result of unhealthy lifestyle and dietary habits together with predisposing genetic backgrounds, is the main cause of increased cardiovascular mortality and raised overall health expenditure. Despite the growing number of cardiovascular prevention campaigns, the control of cardiovascular risk factors remains largely unsatisfactory worldwide. Unhealthy lifestyles lead to an increased consumption of drugs to achieve target levels of cardiovascular risk factors, namely blood pressure and low-density lipoprotein cholesterol. This phenomenon results in a disproportionate increase in the number of cardiovascular drugs, already in the early stages of disease. Despite current guidelines encourage combination therapies in cardiovascular prevention, the adoption of polytherapy, commonly defined as the use of 5 or more drugs, is extremely frequent and is often paradoxically unsuccessful due to poor patient education and adherence, increased adverse effects and inappropriate drug prescribing. Moreover, increased life expectancy resulting from early treatment of myocardial infarction and improved heart failure management has led to an older population characterized by an increased prevalence of comorbid conditions. This is a further reason for increased prescription of drugs leading to an impairment of patient adherence and increased adverse effects. In order to overcome the emerging problem of polytherapy, the use of a single "polypill" containing a combination of drugs for cardiovascular prevention has been postulated. Such an approach is providing promising results in the management of hypertension and dyslipidemia. However, available evidence is still preliminary and prospective data on cardiovascular outcomes are still lacking. This present article proposes a critical analysis of some open issues related to polytherapy in cardiovascular prevention. PMID- 22781379 TI - [Very late coronary drug-eluting stent thrombosis in a patient with essential thrombocythemia: a case report of a rare association]. AB - Very late coronary stent thrombosis is a rare and dangerous complication associated with the use of drug-eluting stents. From registries and trials only a few predictable risk factors have been identified, though not specifically associated with this phenomenon, such as early discontinuation of dual antiplatelet therapy, diabetes mellitus, renal failure, and complex coronary lesions. Essential thrombocythemia, a rare myeloproliferative disorder characterized by increased platelet count and megakaryocytic hyperplasia in the bone marrow, is rarely associated with ischemic cardiac events or coronary stent thrombosis. We describe a case of very late coronary drug-eluting stent thrombosis in a patient affected by essential thrombocythemia and with a platelet count of 780 000/mm3, presenting with acute myocardial infarction. In our opinion, this case report enriches the poor literature about the association between two so rare conditions; moreover, to our knowledge, this is the first case described in the literature of very late coronary stent thrombosis in a patient with this prothrombotic feature. PMID- 22781380 TI - [Giant left atrium with rheumatic mitral stenosis]. PMID- 22781381 TI - [Building a bridge between cardiologists and surgeons: the consensus document on antiplatelet therapy in patients undergoing surgery after coronary stent implantation]. PMID- 22781383 TI - Overall survival analysis of adjuvant radiation versus observation in stage I testicular seminoma: a surveillance, epidemiology, and end results (SEER) analysis. AB - OBJECTIVE: The standard adjuvant treatment for men with stage I testicular seminoma remains controversial within the literature. We analyzed survival rates in men with stage I seminoma who underwent adjuvant radiation therapy (RT) or observation (OB) after orchiectomy. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute from 1973 to 2003. The primary end points were overall survival (OS) and cause-specific survival (CSS). Multivariate Cox regression models were used to study the significance of clinical variables: age at diagnosis, laterality of primary disease, race, and radiation group. RESULTS: Of 6764 patients eligible for analysis, 5265 were treated with RT and 1499 with OB. After a median follow up of 7.6 years, the 5-, 10-, and 20-year OS rates for the RT versus OB were 97.9 versus 95.0, 94.8 versus 92.2, and 83.5 versus 84.1 (P=0.0047), respectively. The CSS rates for the same time periods were 99.6 versus 98.7, 99.4 versus 98.7, and 99.2 versus 98.7 (P=0.0015), respectively. Adjuvant RT was associated with improved CSS on multivariate analysis with hazard ratio of 0.37 (confidence interval, 0.20-0.70; P=0.0023). CONCLUSIONS: Within this large US population analysis, adjuvant RT was associated with improved OS and CSS compared with OB for men with stage I testicular seminoma. Further studies are needed to determine whether modern RT techniques and field-size reductions may lead to greater improvements in the therapeutic ratio, in light of the trend toward chemotherapy as primary treatment. PMID- 22781382 TI - [Coronary stenting and surgery: perioperative management of antiplatelet therapy in patients undergoing surgery after coronary stent implantation]. AB - The management of antiplatelet therapy in patients with coronary stents undergoing surgery is a growing clinical problem and often represents a matter of debate between cardiologists and surgeons. It has been estimated that about 4-8% of patients undergoing coronary stenting need to undergo surgery within the next year. Surgery represents one of the most common reasons for premature antiplatelet therapy discontinuation, which is associated with a significant increase in mortality and major adverse cardiac events, in particular stent thrombosis. In addition, surgery confers an additional risk of perioperative cardiac ischemic events, being high in these patients because of the pro inflammatory and pro-thrombotic effects of surgery. Current international guidelines recommend to postpone non-urgent surgery for at least 6 weeks after bare metal stent implantation and for 6-12 months after drug-eluting stent implantation. However, these recommendations provide little support with regard to managing antiplatelet therapy in the perioperative phase in case of urgent operations and/or high hemorrhagic risk. Furthermore, ischemic and hemorrhagic risk is not defined in detail on the basis of clinical and procedural characteristics. Finally, guidelines shared with cardiologists and surgeons are lacking. The present consensus document provides practical recommendations on the management of antiplatelet therapy in the perioperative period in patients with coronary stents undergoing surgery. Cardiologists and surgeons contributed equally to its creation. An ischemic risk stratification has been provided on the basis of clinical and procedural data. All surgical interventions have been defined on the basis of the hemorrhagic risk. A consensus on the most appropriate antiplatelet regimen in the perioperative phase has been reached on the basis of the ischemic and hemorrhagic risk. Dual antiplatelet therapy should not be withdrawn for surgery at low bleeding risk, whereas aspirin should be continued perioperatively in the majority of surgical operations. In the event of interventions at high risk for both bleeding and ischemic events, when oral antiplatelet therapy withdrawal is required, perioperative treatment with short acting intravenous glycoprotein IIb/IIIa inhibitors (tirofiban or eptifibatide) should be considered. PMID- 22781384 TI - Ventriculolumbar perfusion chemotherapy for the treatment of leptomeningeal carcinomatosis: a phase I study with pharmacokinetic data. AB - OBJECTIVES: To define the maximum tolerated dose, toxicities, and pharmacokinetics of the ventriculolumbar perfusion (VLP) chemotherapy for leptomeningeal carcinomatosis, according to different modes of administration, perfusion rate, and daily methotrexate (MTX) dose. METHODS: For bolus injection modes, a designated MTX dose was given every 12 hours, for 3 consecutive days, with artificial cerebrospinal fluid perfusion. The starting daily MTX dose was 40 mg for 40 mL/h perfusion, and 24 mg for 20 mL/h, respectively. Although in continuous infusion modes, MTX premixed in artificial cerebrospinal fluid was infused for 3 consecutive days. The dose-limiting toxicity (DLT) was defined to be equal to or more than grade 3 side effects, as per the Common Terminology Criteria for Adverse Events. RESULTS: The perfusion rate of 40 mL/h provoked perfusion-related symptoms, such as nausea/vomiting and insomnia, and revealed DLTs including encephalopathy in more than 1/3 of patients in both administration modes when the daily MTX dose of 40 mg was given. The schedule of 20 mL/h perfusion with the daily MTX dose of 24 mg showed milder perfusion-related side effects and provoked no DLT in both administration modes. The relationship between the peak MTX concentration and encephalopathy was not statistically significant. Of 19 patients with increased intracranial pressure, the intracranial pressure was normalized in 14 patients after VLP therapy. CONCLUSIONS: This study disclosed the VLP chemotherapy with a perfusion rate of 20 mL/h and the daily MTX dose of 24 mg could be adopted for future study. PMID- 22781385 TI - Randomized feasibility study of de-escalated (every 12 wk) versus standard (every 3 to 4 wk) intravenous pamidronate in women with low-risk bone metastases from breast cancer. AB - OBJECTIVES: Despite substantial variability in individual risk of skeletal complications, patients with metastatic bone disease are treated with bisphosphonates at the same dose and dosing interval. This study assessed the feasibility of conducting a randomized trial of less frequent bisphosphonate administration in women with breast cancer and low-risk bone metastases. METHODS: A randomized feasibility study was conducted. Patients receiving intravenous bisphosphonates for >=3 months and with low-risk baseline serum C-telopeptide (CTx) levels (<600 ng/L) were assigned to pamidronate 90 mg intravenously every 3 to 4 weeks (control) or every 12 weeks (de-escalated). CTx, bone alkaline phosphatase, and pain scores (Brief Pain Inventory and Functional Assessment of Cancer Therapy-Bone Pain) were collected every 12 weeks for 48 weeks. RESULTS: Fifty-four patients were approached, 44 consented, and 38 were randomized. Median age was 55 (range, 29 to 77) and median baseline CTx was 163 ng/L (range, 10 to 526). Fourteen control group participants (73.7%) and 13 de-escalated group participants (68.4%) maintained CTx in the low-risk range (P=0.64). All patients changing to higher-risk range had progressive extraskeletal disease. Compared with the control group, there was a time-dependent increase in CTx in the de escalated group. There were no significant differences in bone alkaline phosphatase, Brief Pain Inventory, or Functional Assessment of Cancer Therapy Bone Pain. CONCLUSIONS: It is feasible to conduct randomized trials of de escalated pamidronate in low-risk women treated with >=3 months of prior bisphosphonate therapy. De-escalated scheduling satisfied our predefined definition of noninferiority compared with 3- to 4-weekly treatment. Larger trials should assess whether increasing CTx levels with de-escalated therapy lead to higher rates of skeletal complications. PMID- 22781386 TI - Incidence of subclinical nodal disease at the time of salvage surgery for locally recurrent head and neck cancer initially treated with definitive radiation therapy. AB - OBJECTIVES/HYPOTHESIS: To estimate the incidence of subclinical nodal disease at the time of isolated local recurrence (LR) after chemoradiotherapy for an initially staged N0 head and neck squamous cell carcinoma. METHODS: We retrospectively reviewed 44 patients who underwent salvage surgery with or without elective neck dissection (END) for an isolated LR between 1997 and 2010. The incidence of subclinical nodal disease was determined from the pathology reports and from clinical neck failures. RESULTS: Thirty patients received END. The overall incidence of subclinical nodal disease in patients with dissected necks was 10% (3/30 patients). The rate of regional control for the 14 observed necks was 100%. Three-year local control and overall survival rates for the END and non-END cohorts were 71% versus 73% (P=0.80) and 55% versus 64%, respectively (P=0.40). CONCLUSIONS: The risk of subclinical nodal disease is low for patients with an isolated LR after chemoradiotherapy. PMID- 22781387 TI - Radiotherapy in the management of giant cell tumor of bone. AB - OBJECTIVES: To evaluate the long-term treatment outcomes for patients with giant cell tumor of bone (GCTB) treated with radiotherapy with or without surgical resection. METHODS: This retrospective review includes 34 patients with GCTB treated with megavoltage radiotherapy between January 1973 and January 2008 at the University of Florida. Patients' ages ranged from 16 to 85 years (median, 29). Tumor sizes ranges from 2.5 to 12 cm (median, 4.8 cm) in the maximum dimension. Twenty-one patients received radiation for gross disease, either de novo (22 patients) or recurrent (12 patients). Thirteen patients were treated with postoperative radiation after gross total resection. The median dose was 45 Gy in both the definitive and adjuvant settings. RESULTS: The median follow-up was 16.8 years. The 5- and 10-year local-control (LC) rates were 85% and 81%, respectively. Six patients developed an isolated local recurrence (2/13 treated postoperatively and 4/21 who were treated for gross disease). All 6 patients who developed a local recurrence were successfully salvaged with surgery; therefore, the ultimate LC rate was 100%. Both the 5- and 10-year freedom from distant metastasis rates were 91%. Three patients developed lung metastases, including 1 patient who experienced GCTB transformation into a high-grade sarcoma. The 5- and 10-year progression-free survival rates were both 78%. CONCLUSIONS: Moderate-dose radiotherapy for GCTB provides a long-term LC >80%, justifying its role as an alternative to morbid surgery. PMID- 22781388 TI - Additional diagnostic value of hybrid SPECT-CT systems imaging in patients with differentiated thyroid cancer. AB - AIM: : Nuclear medicine has entered a new era of multimodality imaging. Single photon emission computed tomography/computed tomography (SPECT/CT) hybrid cameras are relatively new diagnostic tools that have been widely adopted and are present in most nuclear medicine units. SPECT/CT instruments allow functional and morphologic images to be acquired as superimposed (fusion images) in a single session. METHODS: The integration of CT enables better characterization of functional abnormalities identified on planar and SPECT scintigraphy by offering structural information. It thus highly improves accuracy compared with conventional scintigraphy. RESULTS AND CONCLUSIONS: The combination of functional information and anatomic localization has the potential to influence medical practice with newer imaging algorithms. This review presents the current evidence and potential indications of SPECT/CT imaging in the initial staging, treatment, and follow-up of patients with differentiated thyroid cancer. PMID- 22781389 TI - Stereotactic body radiotherapy in the treatment of adrenal metastases. AB - OBJECTIVES: To evaluate the dosimetry, clinical outcomes, and toxicity of patients treated with stereotactic body radiotherapy (SBRT) for adrenal metastases. MATERIALS AND METHODS: From February 2009 to February 2011, a total of 13 patients were treated with SBRT for metastases to the adrenal glands. Median age was 71 years (range, 60.8 to 83.2). Primary sites included lung (n=6), kidney (n=2), skin (n=2), bladder (n=1), colon (n=1), and liver (n=1). Nine patients had metastases to the left adrenal gland and 4 to the right. The median prescribed total dose was 45 Gy (range, 33.75 to 60 Gy), all in 5 fractions. RESULTS: Median follow-up for living patients was 12.3 months (range, 3.1 to 18 mo). Twelve of the 13 patients (92.3%) were evaluable for local control (LC). The crude LC rate was 100%, with no cases of local or marginal failure. Two patients had a complete response to treatment, 9 patients had a partial response, and 1 patient displayed stable disease. One-year overall survival and distant control were 62.9% and 55%, respectively. Median OS was 7.2 months (range, 2 to 18 mo). Grade 2 nausea was noted in 2 patients. CONCLUSIONS: SBRT seems to be a safe and effective measure to achieve LC for adrenal metastases. PMID- 22781391 TI - Radiation therapy for breast cancer patients who undergo oncoplastic surgery: localization of the tumor bed for the local boost. AB - INTRODUCTION: Oncoplastic reconstructive surgery is performed in select patients with breast cancer to allow conservation treatment when the lumpectomy would be expected to have a poor cosmetic outcome. These techniques not only rearrange the breast tissue but may also shift the position of the tumor bed. The oncoplastic incision may have no relationship to the tumor bed. Although use of whole-breast radiation therapy (RT) is straightforward, difficulties in localization of the tumor bed for the local RT boost have not been investigated. MATERIALS AND METHODS: A retrospective review was performed of 25 patients with 26 cancers who received RT after breast conservation surgery with oncoplastic reconstruction. RESULTS: Among 11 patients with a minimum of 4 surgical clips placed at tumor resection, 8 (73%) had the final tumor bed extend beyond the original breast quadrant or be completely relocated into a different region. In 3 (27%) cases, the clinical treatment volume was 2 to 3 separated regions within the breast. DISCUSSION: For breast cancer patients who have had oncoplastic surgery, the tumor bed is frequently more extensive and possibly relocated compared with original presentation. Placement of surgical clips after tumor resection and before oncoplastic reconstruction may be the most accurate method to localize the RT local boost field. PMID- 22781390 TI - FOLFOX-4 regimen or single-agent gemcitabine as first-line chemotherapy in advanced biliary tract cancer. AB - OBJECTIVES: We conducted a retrospective cohort study to compare 2 different chemotherapy regimens for advanced biliary tract cancer (BTC). METHODS: Records of patients consecutively treated in our institution for advanced BTC from 2001 to 2006 were retrieved. Chemotherapy treatment with FOLFOX-4 regimen was routinely offered as first option; gemcitabine (GEM) as single agent was proposed as an alternative option to patients who refused central venous catheter implantation. Toxicity, overall response rate, progression-free survival (PFS), and overall survival (OS) obtained with the 2 treatments were evaluated. RESULTS: Twenty-two patients were treated with FOLFOX-4, whereas 18 patients received GEM. In the FOLFOX-4 group, the overall response rate was 13.6% (95% confidence interval [CI], 4.7-33.3), with 1 complete response and 2 partial responses, and 54.5% (95% CI, 34.7-73.1) of disease control rate (complete response+partial response+stable disease). Median OS was 14.1 months (95% CI, 9.1-18.8) and median PFS 5.44 months (95% CI, 3.2-6.3). In the GEM group, we observed no objective response, whereas 27.7% (95% CI, 12.5-50.9) obtained disease control. Median OS was 8.3 months (95% CI, 4.7-12.9) and median PFS 3.9 months (95% CI, 2.2-5.4). Toxicity, mainly hematological, was acceptable for both treatments. On a multivariable Cox model including a propensity score, only the performance status and chemotherapy regimen were confirmed as strong predictors of OS, with an hazard ratio of 0.49 (95% CI, 0.24-0.99) in favor of FOLFOX-4. CONCLUSIONS: The combination chemotherapy with oxaliplatin and 5-fluorouracil is well tolerated and seems to provide prolonged survival than GEM alone in advanced BTC treatment, but further randomized trials are warranted. PMID- 22781392 TI - An open-label phase I pilot study of continuous intrapleural infusion of escalated doses of methotrexate in malignant pleural mesothelioma. AB - OBJECTIVES: The aim of this study was to evaluate the toxicity from escalated methotrexate (MTX) doses infused intrapleural over 5 days and to determine pleural and systemic drug levels with this chemotherapeutic approach. PATIENTS AND METHODS: Five patients with malignant pleural mesothelioma were treated with 3 cycles of intrapleural MTX infused through a pigtail catheter inserted in the pleural space. MTX levels were estimated in the pleural fluid and serum once daily throughout the treatment cycles. Fourteen days between cycles were calculated from the last day of the previous one. The total dose for each cycle was infused over 5 days with simultaneous intravenous calcium folinate. The total cycle dose for the first, second, and third cycles were: 300, 501, and 750.5 mg/m, respectively. RESULTS: The mean serum MTX level was 1.72 umole/L, whereas that of the pleural fluid was 503.224 umole/L. The mean serum/pleural ratio was 0.00396, whereas the pleural/serum ratio was 396.21. No remarkable toxicity was observed in the 5 patients except for patient 1 who developed fluid leakage around the puncture site. Patient 2 developed grade I hepatotoxicity and both patients developed grade I pleuritic chest pain and dry irritative cough. CONCLUSIONS: This study demonstrates no grade II toxicity from 750.5 mg/m of MTX infused intrapleural over 5 days. This approach allows attaining MTX pleural levels that are 95 to 3000 times higher than systemic serum levels, with minimal toxicity. The results mandate performing this trial on a wider scale as a preliminary step for a formal phase II study. PMID- 22781394 TI - FLIP: a flop for execution signals. AB - Resistance to apoptosis is one of the established hallmarks of cancer cells. This is a function of an imbalance between the proteins that facilitate death execution and those that inhibit apoptosis or promote cell proliferation. The anti-apoptotic protein, FLICE inhibitory protein (FLIP), first identified as a viral protein, is over-expressed in a variety of human pathologies. Initial observations linked FLIP expression to inhibition of death receptor induced apoptosis, due to its structural homology to the cysteine protease, caspase-8. FLIP impedes full processing of pro-caspase-8 to its active form and its release to the cytosol, and by doing so blocks apoptotic signaling downstream of the membrane death initiating signaling complex (DISC). Recent observations have highlighted the complex regulation of this protein and its cross talk with diverse signaling networks and metabolic processes. As FLIP expression is directly associated with chemotherapy resistance, a better understanding of its genomic organization, gene transcription, as well as post-transcriptional regulation could yield novel targets with potential therapeutic implications against drug refractory cancers. In this short review, we provide a brief overview of the structural and functional biology of this somewhat complex protein with direct relevance to carcinogenesis. PMID- 22781393 TI - The combination of RAD001 and NVP-BKM120 synergistically inhibits the growth of lung cancer in vitro and in vivo. AB - This study focuses on determining whether the combination of NYP-BKM120 (BKM120) and RAD001 exerts enhanced therapeutic effect against lung cancer. The combination of BKM120 and RAD001 exerted synergistic inhibitory effects on the growth of lung cancer cells both in culture and in mouse xenograft model. This combination abrogated RAD001-induced Akt phosphorylation and exerted enhanced suppressive effect on 4EBP1 phosphorylation. Collectively, we suggest that the combination of RAD001 and BKM120 may be an effective regimen for treatment of lung cancer, hence warranting further evaluation of the combination in the clinic. PMID- 22781395 TI - The dual role of fibulins in tumorigenesis. AB - The human fibulin family consists of seven complex extracellular glycoproteins originally characterized as components of elastic fibers in connective tissue. However, beyond its structural role, fibulins are involved in complex biological processes such as cell adhesion, migration or proliferation. Indeed, they have proved to be essential elements in normal physiology, as shown by mouse models lacking these proteins, that evidence several developmental abnormalities and pathological features. Their relevance is also apparent in tumorigenesis, an aspect that has started to be intensely studied. Distinct fibulins are expressed in both tumor and stromal cells and are subjected to multiple expression regulations with either anti or pro-tumor effects. The mechanistic insights that underlie these observations are now commencing to emerge, portraying these proteins as very versatile and active constituents of connective tissue. The aim of this review is to highlight the most relevant connections between fibulins and cancer. PMID- 22781378 TI - [Heart failure in Italian intensive cardiac care units: data from the BLITZ-3 survey]. AB - BACKGROUND: Only limited information about clinical characteristics, diagnostic procedures and therapeutic options is available in patients admitted to an intensive cardiac care unit (ICCU) for heart failure. The aim of this study was to evaluate causes of admission, clinical characteristics, diagnostic and therapeutic options, and outcome of patients admitted for heart failure in the ICCU network. METHODS: The BLITZ-3 Registry prospectively included patients admitted by 332 Italian ICCUs. Data of the patients admitted with a principal diagnosis of heart failure are analyzed. RESULTS: From April 7 to 20, 2008, 6986 consecutive patients with acute cardiac conditions were admitted to ICCUs; 966 (14%) out of 6986 patients were admitted for acute heart failure. Heart failure was the second cause of admission after acute coronary syndromes (52%). Mean age of patients admitted for heart failure was 73 years, 42% were female, and diabetes accounted for 32% of heart failure patients. Most patients were admitted to the emergency department (62%), and were discharged by the cardiology ward (65%). Median length of stay in the ICCU was 4 days, and during the stay in ICCU 5% of the patients with heart failure died. Advanced age and elevated creatinine values were associated with a higher risk of death. Echocardiography was performed in 79% of heart failure patients, coronary angiography in 10%, assisted ventilation in 15%, ultrafiltration in 3%, and right catheterization in 1%. Diuretics were administered in 93% of patients admitted for acute heart failure, intravenous nitrates in 41%, inotropes in 22%, beta-blockers in 42%, angiotensin converting enzyme inhibitors or angiotensin receptor blockers in 66%. CONCLUSIONS: In a nationwide survey, acute heart failure accounted for 14% of hospital admissions in ICCUs. Patients admitted for heart failure are usually old, with frequent comorbidities. Diagnostic and therapeutic procedures are rarely used, with the exception of echocardiography. PMID- 22781396 TI - Histone deacetylase inhibitor, apicidin, inhibits human ovarian cancer cell migration via class II histone deacetylase 4 silencing. AB - This study examined the molecular mechanisms of apicidin in the modulation of human ovarian cancer SKOV-3 cells invasion and migration. Apicidin markedly decreased histone deacetylase 4 (HDAC4) expression and blocked cell migration and invasion. Cell migration was inhibited via down-regulation of matrix metalloproteinase-2 (MMP-2) and up-regulation of RECK in the HDAC4-blocked SKOV-3 cells. Apicidin significantly suppressed the binding of HDAC4 to Sp1 binding elements of the RECK promoter via repression of HDAC4. In an in vivo model, apicidin suppressed the growth of transplanted SKOV-3 cells by down-regulating HDAC4 and MMP-2. Apicidin may potentially be used as an anti-cancer agent for inhibition of cancer cell migration and invasion through the repression of MMP-2 which is related to the reduction of HDAC4. PMID- 22781397 TI - Molecular crosstalk between the proteasome, aggresomes and autophagy: translational potential and clinical implications. AB - Targeting the ubiquitin+proteasome protein degradation pathway with the therapeutic agent bortezomib has significantly improved the survival of cancer patients but drug resistance inevitably develops. Aggresomes and the autophagy pathway serve as compensatory protein-clearance mechanisms that eradicate potentially toxic proteins to promote resistance to proteasome inhibitors and, hence, tumor survival. Pre-clinical evidence has emerged to demonstrate active crosstalk between these protein degradation pathways and has revealed novel therapeutic targets and strategies. Translational research and clinical trials are now focused on these pathways to prevent the emergence of drug resistance, enhance apoptosis and further improve the survival of cancer patients. PMID- 22781399 TI - Induced power changes the sense of agency. AB - Power differentials are a ubiquitous feature of social interactions and power has been conceptualised as an interpersonal construct. Here we show that priming power changes the sense of agency, indexed by intentional binding. Specifically, participants wrote about episodes in which they had power over others, or in which others had power over them. After priming, participants completed an interval estimation task in which they judged the interval between a voluntary action and a visual effect. After low-power priming, participants judged intervals to be significantly longer than judgments after high-power or no priming. Thus, intentional binding was significantly changed by low-power, suggesting that power reduces the sense of agency for action outcomes. Our results demonstrate a clear intrapersonal effect of power. We suggest that intentional binding could be employed to assess agency in individuals suffering from anxiety and depression, both of which are characterised by reduced feelings of personal control. PMID- 22781398 TI - NSC 74859 enhances doxorubicin cytotoxicity via inhibition of epithelial mesenchymal transition in hepatocellular carcinoma cells. AB - Doxorubicin-based therapy is not effective for the treatment of hepatocellular carcinomas (HCCs), which often undergo epithelial-mesenchymal transition (EMT) during tumor progression. Activation of signal transducer and activator of transcription 3 (STAT3) is associated with chemosensitivity and may contribute to EMT during HCC chemotherapy. Low doses of NSC 78459 (a novel STAT3 inhibitor) have little effect on HCC cell proliferation, but efficiently inhibit STAT3. HuH 7, Hep3B, and HepG2 cells, with epithelial phenotypes, show significantly enhanced doxorubicin cytotoxicity following co-treatment with NSC 74859, whereas mesenchymal SNU-449 cells show no such enhancement. NSC 74859 inhibits STAT3 activity and suppressed doxorubicin-induced EMT in epithelial HCC cells. siRNA mediated STAT3 knockdown resulted in EMT inhibition, which led to attenuation of NSC 74859-mediated chemosensitivity. Our data indicate NSC 74859 co administration enhances doxorubicin cytotoxicity by inhibiting STAT3 in epithelial HCC cells. STAT3 deactivation and associated EMT attenuation contribute to the synergistic anti-tumor effects of combined NSC 74859/doxorubicin therapy. PMID- 22781400 TI - Neuropsychological function and suicidal behavior: attention control, memory and executive dysfunction in suicide attempt. AB - BACKGROUND: Executive dysfunction, distinct from other cognitive deficits in depression, has been associated with suicidal behavior. However, this dysfunction is not found consistently across samples. METHOD: Medication-free subjects with DSM-IV major depressive episode (major depressive disorder and bipolar type I disorder) and a past history of suicidal behavior (n = 72) were compared to medication-free depressed subjects with no history of suicidal behavior (n = 80) and healthy volunteers (n = 56) on a battery of tests assessing neuropsychological functions typically affected by depression (motor and psychomotor speed, attention, memory) and executive functions reportedly impaired in suicide attempters (abstract/contingent learning, working memory, language fluency, impulse control). RESULTS: All of the depressed subjects performed worse than healthy volunteers on motor, psychomotor and language fluency tasks. Past suicide attempters, in turn, performed worse than depressed non-attempters on attention and memory/working memory tasks [a computerized Stroop task, the Buschke Selective Reminding Task (SRT), the Benton Visual Retention Test (VRT) and an N-back task] but not on other executive function measures, including a task associated with ventral prefrontal function (Object Alternation). Deficits were not accounted for by current suicidal ideation or the lethality of past attempts. A small subsample of those using a violent method in their most lethal attempt showed a pattern of poor executive performance. CONCLUSIONS: Deficits in specific components of attention control, memory and working memory were associated with suicidal behavior in a sample where non-violent attempt predominated. Broader executive dysfunction in depression may be associated with specific forms of suicidal behavior, rather than suicidal behavior per se. PMID- 22781402 TI - Evaluation of the prevention programs that work curriculum to teach use of public health evidence to community practitioners. AB - Training on use of evidence may increase the adoption of evidence-based strategies in communities. The purpose of this study was to evaluate the Prevention Programs That Work training. This article summarizes the training modules and evaluation results from three trainings conducted in Spring 2009. The training teaches practitioners from community-based organizations to locate, choose, adopt or adapt, and evaluate an evidence-based program. Participants completed a pretest and posttest that covered competencies related to use of evidence, demographics, and feedback on training. A total of 47 participants attended three trainings. They represented coordinators, directors, nurses, and outreach workers. Participants showed the greatest increases in the following competencies: locate evidence-based resources, narrow search results of potential programs or strategies to reflect programmatic specifics, define steps in the adaptation process, and discuss factors during each phase of implementation. According to participants, the most useful aspects of the training content were the areas that covered program implementation, adaptation, and evaluation. A workshop can increase competencies to use evidence-based strategies among community practitioners. Building competencies is a critical initial step in promoting the dissemination of evidence-based strategies and helping practitioners use a systematic process to select an evidence-based intervention and implement the programs with fidelity. PMID- 22781403 TI - [Relationship between hyperuricemia and chronic kidney disease in Pudong New Area of Shanghai]. AB - OBJECTIVE: To investigate the relationships between hyperuricaemia, serum uric acid (SUA) level and the chronic kidney disease (CKD) in adult residents of Pudong New Area, Shanghai. METHODS: 3326 residents aged 20 - 80 years were randomly selected from Pudong New Area, Shanghai through multistage sampling and interviewed between April and July of 2008. Fasting blood sample and morning ovid urine sample were collected for each participant for testing of SUA, serum creatinine, urinary albumin and creatinine. Both urine albumin to creatinine ratio (ACR) and glomerular filtration rate (GFR) were calculated to estimate the renal function. RESULTS: The overall prevalence of CKD was 16.0% (age standardized 13.2%). The mean values of estimated GFR in participants with CKD and without CKD were (89.19+/-27.25) and (105.88+/-98.37) ml*min(-1)*(1.73 m2)( 1), respectively. The prevalence rates of CKD in serum uric acid quartiles: first quartile, less than 4.2 mg/dl; second quartile, 4.2-5.0 mg/dl; third quartile, 5.0-6.0 mg/dl; and fourth quartile, 6.0 mg/dl or more were 13.9%, 15.0%, 15.8%and 19.4% (P<0.05) respectively, increasing along with the increase of SUA among both sexes. Compared to the serum uric acid first quartile, the multivariate-adjusted odds for CKD of the second, third and fourth quartiles were 1.19 [95% confidence interval (CI): 0.90-1.58], 1.27 (95%CI: 1.02-1.70), 1.28 (95%CI: 1.10-1.68), respectively. CONCLUSION: Hyperuricaemia was independently associated with the increased prevalence of CKD among population living in the Pudong New Area, Shanghai. PMID- 22781401 TI - Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells. AB - BACKGROUND: Diabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 omega-3) and eicosapentaenoic acid (EPA, 20:5 omega-3). The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn2+ is essential for the activity of Delta6 desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs) alpha-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood. METHODS: RF/6A cells were treated with different concentrations of high glucose, alpha-linolenic acid and linoleic acid and Zn2+. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF) secretion were evaluated. RESULTS: Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA) and alpha-linolenic acid (ALA), while the saturated fatty acid, palmitic acid was ineffective. A dose response study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn2+ and ALA. ALA was more potent that Zn2+. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed high-glucose-induced VEGF secretion by RF/6A cells. CONCLUSIONS: These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage. PMID- 22781404 TI - [Study on the prevalence rate of abdominal obesity in 9 rural communities from Hanzhong area of Shaanxi province]. AB - OBJECTIVE: The objective of this study was to investigate the prevalence rate of abdominal obesity and to explore the associated risk factors in rural communities from Hanzhong area, Shaanxi province, and to provide baseline data for further targeted intervention programs. METHODS: A cross-sectional study was conducted among all the participants with questionnaires, interview and physical examination. Nine townships were selected in Hanzhong area, followed by one village randomly chosen from the selected township, using the stratified random sampling method. RESULTS: There were 3030 participants in this survey, among which 3021 samples were valid, including 1048 males and 1973 females. The overall prevalence rate of abdominal obesity was 38.9% (standardized rate as 33.4%) in rural communities of Hanzhong, and the prevalence rate on males abdominal obesity (35.0%) was significantly lower than that of females (40.9%). It was found that following factors as: being male, married, having more household wealth, frequent consumption of fried food, non-engagement of agricultural labor work, being nonsmoker or ex-smoker, spending longer time on watching-TV etc. were positively associated with the bigger odds of having abdominal obesity when using the logistic regression analysis. Meanwhile, data from this study indicated that factors as: at younger age, frequent participation in agricultural labor, under artificial feeding, with more years of education, less frequency of pregnancy etc. were negatively related to the prevalence of female abdominal obesity. CONCLUSION: The prevalence rate of abdominal obesity in Hanzhong area, Shaanxi province was significantly higher than the national average level which called for the development of related intervention programs to prevent chronic diseases associated with gender related-obesity in Hanzhong. PMID- 22781405 TI - [Folate status in the red blood cell and related geographical differences among 810 with 65- to 74-year-old population of two counties in Southern and Northern China]. AB - OBJECTIVE: To assess the red blood cell (RBC) folate status among Chinese elderly population and its geographical differences between Southern and Northern regions, and to evaluate the correlation between RBC and plasma folate. METHODS: This study was conducted in two counties of Jiangsu and Hebei provinces of China. A total of 810 individuals aged 65-74 years were recruited. RBC folate in blood samples was measured by microbiological assay. Data on RBC folate was log transformed before analysis. Means of RBC folate concentration were compared by t test, and the prevalence rates of RBC folate deficiency for different characteristics were compared by chi2 test. RESULTS: The geometric mean of RBC folate concentration was 1083.3 nmol/L (95%CI: 1034.1-1134.8) among the Southerners and 489.1 nmol/L (95%CI: 466.7-512.6) among the Northerners, with the former being 2.2 times of the latter (t=23.684, P<0.001). The prevalence rates of RBC folate deficiency were 1.0% in the South and 28.9% in the North (chi2=124.06, P<0.001). The concentrations of RBC folate were positively correlated with plasma folate (r=0.49, P<0.001). After adjustment for region, sex, age, BMI, education, exposure to tobacco smoking and alcohol consumption, the correlation remained significant (r=0.38, P<0.001). CONCLUSION: In 810 Chinese elderly population aged 65-74 from the two counties, Southerners had a higher RBC folate concentration and a lower deficiency prevalence than those in the Northerners. The RBC folate concentration was positively associated with plasma folate. PMID- 22781406 TI - [A prevalence study on mild cognitive impairment among the elderly populations of Mongolian and Han nationalities in a pastoral area of Inner Mongolia]. AB - OBJECTIVE: To understand the epidemiological characteristics and distribution of mild cognitive impairment (MCI) in elderly populations from Mongolian and Han nationalities living in the pastoral areas of Inner Mongolia Autonomous Region of China. METHODS: According to the MCI clinical diagnostic criteria from Diagnostic and Statistical Manual of Mental Disorders 4th revised edition (DSM-IV) by American Psychiatric Association, the individuals under study were at the age of 55 or over, with Mongolian or Han ethnicities and living in the pastoral area of Inner Mongolia. RESULTS: The crude MCI morbidity rates of Mongolian and Han of the study populations in the pastoral area of Inner Mongolia Autonomous Region of China was 19.48% (1782/9146) and the standardization morbidity was 18.98%. The crude MCI morbidity rates of both Mongolian and Han ethnicities were 17.46% (the standardization morbidity was 16.99%) and 20.60% (the standardization morbidity was 19.98%), respectively. There showed a significant positive correlation between the crude morbidities and age, also significantly increasing with the latter. In the Mongolian population, the morbidity increased from 12.17% at the age 55-59 to 27.78% at 85 while in the Han population, the morbidity increased from 15.50% at the age 55-59 to 23.53% at 85. In both the populations of Mongolian and Han, there was a statistically difference found between the morbidities of MCI (chi2=13.229, P=0.000). The morbidity was higher in Hans than in the Mongolians. However, there was no statistically significant difference noticed between the morbidities of MCI in the Mongolian males and females (chi2=2.376, P=0.123). There was statistically significant difference found between the morbidities of MCI in the Han males and females, with females having higher risk than males (chi2=24.470, P=0.000). CONCLUSION: The morbidity of MCI in the elderly Mongolian and Han populations from the pastoral area of Inner Mongolia Autonomous Region of China was considered to be quite high and correlated to age and gender. PMID- 22781407 TI - [The prevalence of HIV infection and sexual behaviors among men who have sex with men and women in Chengdu and Guangzhou, China]. AB - OBJECTIVE: To understand the status of HIV infection and sexual behaviors with men and women among men who have sex with men and women (MSMW) and documented for HIV epidemic among men who have sex with men to the general population. METHODS: 300 participants were recruited by using "snowballing" sampling in Chengdu and Guangzhou, respectively. Participants completed the questionnaire and HIV test. The questionnaire included social demographic characteristics, number of male sexual partners, sexual behaviors and condom use in the past 6 months. Relations with female sexual partners, vaginal intercourse and condom use in the past 12 months were also studied. RESULTS: Of the 600 participants, the overall prevalence of HIV infection was 26.2% and the detection rate of HIV-positives in this survey was 8.5%. In the past 6 months 28.0% of the participants had 5 or more male sexual partners and the percentage of MSMW who had used condoms consistently during anal sex intercourse with men, was 44.2%. Of the participants, 52.3% had used condoms in the last three anal sex events and 63.0% in the last event. In the past 12 months, 86.0% of the participants who had vaginal sex with female partners and the proportions of MSMW who had wife, girlfriend, lover, female casual partner and female commercial partner were 65.0%, 27.2%, 1.5%, 12.7%, 4.5%, respectively. About a third of the MSMW had always used condoms when having vaginal sex in the past 12 month. In the last three vaginal sex events, the proportion of participants who had never used condoms was 36.5%. In the past 6 months, 55.7% of the MSMWs had used condoms consistently during anal sex with men in Chengdu, which was higher than those MSMW in Guangzhou (32.7%). In the past 12 months, the proportion of MSMW who had used condoms consistently during vaginal sex was 38.3%, which was higher than MSMW of Guangzhou (25.3%). Among those HIV-positive MSMWs, 91.1% had anal sex with men in the past 6 months and 49.7% HIV-positive MSMW had used condoms consistently during anal sex with men. The number of HIV-positive MSMW who had used condoms in the last or last three anal sex events with men, accounted for 60.5% and 69.4%, respectively. In the past 12 months, 82.8% of the HIV-positive participants had vaginal sex with women. Of the HIV-positive participants, 42.0% used condoms consistently and the percentage of HIV-positive MSMWs who used condom during last three vaginal sexes was 47.8%. In the past 6 months, the percentage (4.3%) of MSMW who were HIV-positive prior to the survey and never used condoms during anal sex with men was lower than the percentage (22.0%) of MSMW who were HIV-positive found in this survey. In the past 12 months 12.9% of the MSMW who were HIV positive prior to the survey never used condoms when having vaginal sex event, which was lower than MSMW (46.3%) who were HIV positive in this survey. CONCLUSION: The prevalence of HIV infection had reached a quite high level and with high rates of unprotected anal sex with men and vaginal sex with women among MSMWs, indicating that the inherent bridging aspect of MSMW might accelerate the spreading of HIV infection to the general population. PMID- 22781408 TI - [Exposure to avian influenza virus and the infection status of virus among people breeding or butchering ducks in the suburb of Beijing]. AB - OBJECTIVE: To understand the exposure and the infection status of virus among people engaging in breeding or butchering ducks in the suburb of Beijing. METHODS: People from six districts (Daxing, Fangshan, Huairou, Miyun, Shunyi, Tongzhou) who engaged in breeding or butchering ducks were studied and the status of infecting avian influenza virus was obtained by testing antibody level in serum. Information on demographic characteristics, status of regular exposure and exposure to sick or dead poultry were collected through a self-designed questionnaire. RESULTS: 1741 people were involved in this study in which 313 (18.0%) were workers in duck-breeding enterprise, 562 (32.3%) were workers in duck slaughterhouse, 261 (15.0%) farmers were in individual small-scale duck farms, 605 (34.7%) were farmers raising duck in backyard. Among farmers raising duck in backyard, the percentage of people whose ducks ever contacted with wild birds was higher than the other three groups (66.8%) (P<0.05). Among farmers who bred their ducks in the backyard (35.2%) and those abattoir workers (31.3%), the percentage of people who had contacted ducks but not been vaccinated with avian influenza vaccine was higher than the other two groups (P<0.05). Regarding the status on cleaning and disinfection among the studied farmers who had bred their ducks in the backyard, the percentage of people who had closer contact with ducks would clean the settings more than 4 times per month (8.8%) and disinfected those places more than 12 times per year (27.3%) but still lower than the other three groups (P<0.05). Among those farmers who bred ducks in the backyard, the percentage of people who had ever touched duck with their hands was high (34.4%) (P<0.05). Regarding exposure to sick or dead poultry, higher proportion was found among those who had ever closely contacted sick or dead poultry commercial duck raisers (36.1%) and individuals who raise large amount of ducks (36.0%). 70.8% of the individual duck raisers had never taken any protective measures when closely contacting the sick or dead poultry. Among 1741 samples, 0 were positive to avian influenza virus H5 and H7 subtypes. 12 were positive to H9 subtype (positive rate was 0.7%), in which 10 were farmers raising ducks in backyard (the positive rate of 1.7%). Differences between H9 subtype antibody positive rates difference in 4 population groups were statistically significant (chi2=13.699, P<0.05). CONCLUSION: Farmers who bred their ducks in the backyard had greater risk of contracting the avian influenza. Individual duckers who raise ducks in large scale and the farmers who bred their ducks in the backyard were in lack of protective measures when contacting the sick or dead poultry. Our findings suggested that some intervention measures should be taken to reduce the risk of avian influenza infection. PMID- 22781409 TI - [Using multivariate multilevel logistic model to study the influential factors of attitudes related to the Punishment on Smoking, among the residents in Guangzhou]. AB - OBJECTIVE: To explore the attitudes towards the Smoking Ban policy and the bias in different levels of related society sanctions so as to provide evidence for implementing anti-smoking measures in the public places. METHODS: A multi univariate-multilevel logistic model was developed to find the relation between penalty attitudes and the covariates' effects. RESULTS: 74.6% (3647/4892) and 61.2% (2994/4892) of the residents agreed to punish either the managers of public places or to the smokers. The two kinds of attitude were associated (chi2=1253.45, P<0.0001). Residents being female, aged between thirty and fifty nine years old, having had higher than college education, being non-current smokers, with high scores on knowledge of tobacco control, tended to have the attitude of punishing the public place managers and smokers. However, those persons exposed to everyday secondhand smoke or being non-current smokers, tended to punish the smokers in the generalized Wald test. CONCLUSION: There was strong evidence noticed that most of the residents in Guangzhou had supported the 'tobacco control penalty'. Factors as age, sex, level of education received, knowledge on hazards of smoking, being current smokers and under secondhand smoke exposure were the influencing factors. Non-current smokers and those who exposed to secondhand smoke everyday, would prefer to take different penalties policies. PMID- 22781410 TI - [A case-control study on the risk factors of work-related acute pesticide poisoning among farmers from Jiangsu province]. AB - OBJECTIVE: To explore the risk factors on cases regarding work-related acute pesticide poisoning among farmers of Jiangsu province. METHODS: A population based, 1:2 matched case-control study was carried out, with 121 patients as case group paired by 242 persons with same gender, district and age less then difference of 3 years, as controls. Cases were the ones who had suffered from work-related acute pesticide poisoning. A unified questionnaire was used. Data base was established by EpiData 3.1, and SPSS 16.0 was used for both data single factor and multi-conditional logistics regression analysis. RESULTS: Results from the single factor logistic regression analysis showed that the related risk factors were: lack of safety guidance, lack of readable labels before praying pesticides, no regression during application, using hand to wipe sweat, using leaking knapsack, body contaminated during application and continuing to work when feeling ill after the contact of pesticides. Results from multi-conditional logistic regression analysis indicated that the lack of safety guidance (OR=2.25, 95%CI: 1.35-3.74), no readable labels before praying pesticides (OR=1.95, 95%CI: 1.19-3.18), wiping the sweat by hand during application (OR=1.97, 95%CI: 1.20 3.24) and using leaking knapsack during application (OR=1.82, 95%CI:1.10-3.01) were risk factors for the occurrence of work-related acute pesticide poisoning. CONCLUSION: The lack of safety guidance, no readable labels before praying pesticides, wiping the sweat by hand or using leaking knapsack during application were correlated to the occurrence of work-related acute pesticide poisoning. PMID- 22781411 TI - [Coverage on cataract surgery among adults aged 40 or above in a multiethnic rural district of high altitude area in Gongshan county, Yunnan province, China]. AB - OBJECTIVE: To estimate the prevalence of cataract and its surgical coverage rate together with the burden related to bilateral cataract-blindness, among adults aged 40 or above in Gongshan county of Yunnan province and to evaluate the current cataract status and the efficacy of local cataract prevention program. METHODS: Cluster sampling was used. The protocol consisted of personal interview, pilot study, visual acuity checking, measuring the intraocular pressure; slit lamp microscopy and the fundus of the eye examination etc. Cataract was graded clinically using the Lens Opacity Classification System (LOCS) III. Bilateral cataract-blindness burden, bilateral cataract-blindness burden and cataract surgical coverage rate were calculated respectively, using two different criteria. Odds ratios (OR) were compared among different groups regarding age, gender, education, ethnic group and altitude of living area. RESULTS: Among the 1236 eligible residents, 1116 (90.3%) were enrolled in the present study. The prevalence of cataract was 23.8% among adults aged 40 or order. When the bilateral best refractive vision<3/60 was defined as the blindness criterion, the bilateral cataract-blindness burden showed as 1.3%, and cataract blindness surgical coverage rate was 50.0%. When the bilateral presenting vision<6/60 was defined as the blindness criterion, the bilateral cataract-blindness burden was 25.0%, and cataract blindness surgical coverage rate was 12.9%. The cataract surgical coverage rates were much lower and the bilateral cataract-blindness burden much higher in women, illiterates, living in high altitude areas and those who were aged 70 or above. CONCLUSION: Cataract blindness was a serious public health problem in aged individuals and illiteracy in the residents of the studied areas. Poor prevention programs on cataract called for urgent action to be taken. PMID- 22781412 TI - [Estimates and prediction on incidence, mortality and prevalence of lung cancer in China in 2008]. AB - OBJECTIVE: To estimate the incidence, mortality and 5-year prevalence rates of lung cancer in China, in 2008. METHODS: Data from 36 cancer registries and the Third National Death Survey in China (2004-2005) was used to estimate the incidence, mortality and 5-year prevalence rates of lung cancer in China in 2008. Mathematical models were used to predict the lung cancer incidence and mortality rates in the next 20 years. RESULTS: In 2008, the incidence of lung cancer was 522,050 (18.5%) with the incidence rate as 33.5/100,000, which ranked the first among all the cancers. Mortality of lung cancer in China was 452,813 (23.1%) with the mortality rate as 28.7/100,000, which also ranked the first among all the cancers. The 5-year prevalence rate of lung cancer in China was 487,815 (10.6%) with the proportion as 45.6/100,000, which ranked fourth among all the cancers. Lung cancer happened more frequently among people older than 45 years, particularly in males. Our data on prediction showed that the incidence and mortality of lung cancer in China would gradually increase in the next 20 years. CONCLUSION: Lung cancer was the leading cause for both incidence and mortality of all cancers in China and both kept increasing. The key population fell in those older than 45 years, particularly males, that should be under special prevention and control for lung cancer. PMID- 22781413 TI - [Incidence and mortality of larynx cancer in China during 2003-2007]. AB - OBJECTIVE: To analyze the patterns of incidence and mortality on larynx cancer in China. METHODS: Data from 32 Cancer Registries in China were examined, sorted, and analyzed by the National Cancer Registry, to obtain the crude, Chinese national and world age-standardized rates (ASR) of incidence and mortality and their trends. RESULTS: The crude incidence and mortality rates of larynx cancer were 2.04/10(5) and 1.06/10(5) in China during 2003-2007. The rates were higher in males than those in females, and also higher in urban areas than those in rural areas. The highest Chinese ASRs of incidence and mortality of larynx cancer in 32 cancer registries in China were 2.08/10(5) in Zhongshan city, Guangdong province, and 1.58/10(5) in She county, Hebei province respectively. The trend of incidence and mortality of larynx cancer was stable from 2003 to 2007. CONCLUSION: Although both the incidence and mortality of larynx cancer in China were still in low level, comprehensive measures should be carried out to prevent the increase on both the incidence and mortality of larynx cancer. PMID- 22781414 TI - [Mortality trend on chronic obstructive pulmonary disease in Liaoning province, 1984-2010]. AB - OBJECTIVE: To evaluate the mortality trend of chronic obstructive pulmonary disease (COPD) among residents in Liaoning province during the period of 1984 2010. METHODS: The cut-points were ascertained by Monte Carlo Permutation test in COPD mortality trend lines of Poisson regression with Joinpoint Regression Program. The annual percent changes (APC) before and after the cut-points and the average annual percent change (AAPC) of COPD mortality were examined during the period. RESULTS: Significant declining trends on COPD mortality among the urban population during 1984-2010 and that of rural population during 1999-2009 were found. The standardized urban COPD mortality rate by Chinese population declined from 243.93 per 100 thousand in 1984 to 33.13 per 100 thousand in 2010. The urban 26 years AAPC was -5.8%. While the mortality in the rural population decreased from 251.33 per 100 thousand in 1999 to 102.25 per 100 thousand in 2009 in the same population. The rural 10 years' AAPC was -6.8%. The total trend of COPD mortality reduction was mainly resulted from the fast decline of bronchitis mortality. The AAPC of COPD mortality of the urban population was -9.0% and greater than that of the rural population (-6.8%) from 1999 to 2009. The urban population had a lower COPD mortality than that of the rural population. In urban area, males had a higher COPD mortality than females, however, in the rural area, males had a lower COPD mortality than the females. CONCLUSION: The COPD mortality among the residents of Liaoning province declined significantly from 1984 to 2010. Further studies are needed to confirm the viewpoint of WHO that the prevalence of COPD would have a continuous increasing trend in China. PMID- 22781415 TI - [Risk factors for influenza A (H1N1)-associated pneumonia on hospitalized people less than 18 years old in China, 2009-2010]. AB - OBJECTIVE: To describe the epidemiological and clinical features of hospitalized people less than 18 years old with influenza A (H1N1)-associated pneumonia and associated risk factors. METHODS: Through Chinese Reporting System of Influenza A (H1N1), children aged under 18 years who were hospitalized with laboratory confirmed influenza A (H1N1), case report forms and related information on pneumonia were collected between 1 September 2009 and 4 July 2010. Epidemiological and clinical characteristics including demographics, underlying chronic diseases, treatment, complications and clinical outcome etc. were described. Hospitalized children with pneumonia were compared with those without the above mentioned features, through the univariate and multivariate analysis. RESULTS: There were 4240 influenza A (H1N1)-associated hospitalized children with case report forms identified. Of the 4107 influenza A (H1N1)-associated hospitalized children with related information on pneumonia shown in the case report forms, 2289 (55.7%) of them had pneumonia. Hospitalized children with influenza A (H1N1)-associated pneumonia had a younger median age (4.9 year old), when compared with those without pneumonia (13.1 year old, P<0.0001). When compared with the hospitalized children without pneumonia, those hospitalized children with pneumonia were more likely to require intensive care unit care, using mechanical ventilation equipment to develop ARDS, respiratory failure or leading to death. Data from multivariate analysis showed that children aged<6 months (OR=7.08, 95%CI: 4.15-12.06) between 6 and 23 months (aOR=8.26, 95%CI: 6.10-11.20) or between 2 to 4 year old (aOR=9.53, 95%CI: 7.39-12.29) were more likely to develop pneumonia than children aged 5 to 17. Factors as having asthma (OR=12.19, 95%CI: 5.18-28.72), cardiovascular disease (OR=5.19, 95%CI: 1.94 13.90), chronic renal diseases (OR=2.14, 95%CI: 1.02-4.53), chronic hepatic diseases (OR=5.26, 95%CI: 1.40-19.81) and allergy (OR=2.54, 95%CI: 1.64-3.93) were significantly associated with influenza A (H1N1)-associated pneumonia. Risk of complication with pneumonia had an increase when oseltamivir treatment was initiated>2 days after the onset of illness. CONCLUSION: Pneumonia was a common complication among children hospitalized with influenza A (H1N1). Hospitalized children with influenza A (H1N1)-associated pneumonia were more likely to develop either severe clinical courses or outcomes than those without pneumonia. PMID- 22781416 TI - [Status of physical activities among 379 pupils in Beijing]. AB - OBJECTIVE: Using the objective detection devices to explore the physical activity status in order to provide evidence related to the physical activity intervention program on child obesity in elementary students. METHODS: Subjects were elementary students from grades 1-5 of 4 schools in Haidian and Dongcheng districts, Beijing. After measuring their height and weight, an motion sensor was applied to measure physical activities in these 379 pupils. RESULTS: Time on moderate to vigorous physical activities (MVPA) among pupils was 74.09 min and the ratio of meeting the recommended time of physical activity was 68.9%. The MVPA time in males (79.46 min) was more than that in females (66.07 min) (P<0.05), with the ratio of meeting the recommended physical activity time in males (78.0%) also larger than that in females (55.3%) (P<0.05). There was no significant difference between low age group and high age group (P>0.05), however, there showed significant difference in light physical activity time among the normal group, overweight group and the obese group (P<0.05). However, there was no significant difference found in MVPA time among the three groups (P>0.05). CONCLUSION: The ratio of meeting the recommend physical activity time was low. MVPA time should be increased to guarantee the athletic effects and to improve the health status in the pupils. PMID- 22781417 TI - [Prevalence and major risk factors of peripartum thromboembolic disease in different regions of Guangdong province]. AB - OBJECTIVE: To investigate the prevalence and major risk factors of peripartum thromboembolic disease in different regions of Guangdong province. METHODS: Data from 169 218 pregnant women in different regions of Guangdong province from January 2005 to June 2010 were analyzed retrospectively. The prevalence and epidemiological characteristics of thromboembolic disease during pregnancy or puerperium were investigated. RESULTS: Of the studied population, (1) 201 cases (1.30/00) suffered from thromboembolic disease during pregnancy or puerperium including 128 cases of deep vein thrombosis (DVT), 68 cases of cerebral venous thrombosis (CVT) and 5 pulmonary embolism, the prevalence rates were 0.80/00, 0.40/00, and 0.020/00 respectively. (2) Risk factors in different regions showed that, in the Pearl River Delta area, the major risk factors for DVT would include previous or family history of thrombosis, pregnancy complications, with medically involved diseases, prolonged bed rest and pregnancy weight gain>15 kg etc. While in eastern, western, northern parts of Guangdong, the major risk factors for DVT would include pregnancy weight gain>15 kg, prolonged bed rest, preeclampsia, cesarean section and complications during pregnancy. In Pearl River Delta region, the major risk factors for CVT would include eclampsia, preeclampsia, pregnancy complications, prolonged bed rest>3 days, past history or family history of thrombosis. While eclampsia, preeclampsia, advanced age or younger age, pregnancy weight gain>15 kg, complications during pregnancy were the major risk factors for CVT in the eastern, western or northern parts of Guangdong. CONCLUSION: Prevalence and major risk factors of peripartum thromboembolic disease in different regions of Guangdong were different. It was crucial to take effective measures in pregnant women with different epidemiological characteristics and risk factors to prevent and reduce the incidence of peripartum thromboembolic disease. PMID- 22781418 TI - [Relationship between metabolic syndrome and adipokines on diabetes among high risk populations]. AB - OBJECTIVE: To study the relationship between adipokines and metabolic syndrome (MS), and the predictive value of adipokines on diagnosis of MS. METHODS: According to the IDF consensus worldwide definition on MS in 2005, we divided the subjects into 4 groups: 115 in MS0 (with none of MS component); 118 in MS1 (with one MS component); 77 in MS2 (with two MS components) and 104 in MS3 (with none of MS component). Serum levels of leptin, visfatin adiponectin and resistin were measured in these groups, using the enzyme linked immunosorbent assay (ELISA) method. Retinol-binding protein 4 (RBP-4) was assessed by radioimmunoassay (RIA). RESULT: (1) Serum adiponectin level decreased while the serum level of leptin and RBP-4 increased in women with the number of MS components gathered. However, the level of visfatin obviously decreased only in the MS3 phase. The level of resistin showed no changes with MS components gathered. (2) Detection rates of the MS components such as high blood pressure, hyperglycemia, dyslipidemia, insulin resistance and obesity were significantly higher in the Q4 group with high level of leptin when compared to the Q1 group with lower level (odd ratio: Q4/Q1 is 1.3, 1.8, 1.6, 5.2, 3.0 respectively). (3) The higher level of serum RBP 4 was not only associated with greater risk for impaired glucose regulation (odd ratio: Q4/Q1=2.6), but also significantly with the risks for hyperglycemia (odd ratio: Q4/Q1=1.6) dyslipidemia (odd ratio: Q4/Q1=1.9), obesity (odd ratio: Q4/Q1=1.5) and MS (odd ratio: Q4/Q1=2.7). In the Q4 group with higher levels of RBP-4, the positive rates of MS reached 50%. (4) The detection rates of MS components such as dyslipidemia, obesity, hyperglycemia, and insulin resistance were significantly higher in the Q1 group with the lowest level of adiponectin when compared to the Q4 group with the highest level. CONCLUSION: The levels of adipokines, serum adiponectin, leptin and RBP-4 showed significant associations with MS. Our findings suggested that these adipokines might serve as the key factors that participating in MS and could be used as markers for early prediction of MS as well as the new targets for therapy. PMID- 22781419 TI - [Characteristics of traditional risk factors and coronary lesions on coronary heart disease among different sex populations]. AB - OBJECTIVE: This study aimed to determine the prevalence rates of conventional risk factors and to analyze the features of coronary lesions in patients with coronary heart disease (CHD). METHODS: 3765 CHD cases were collected from the General Hospital of PLA in Beijing from 2009 to 2010 (2661 men, 1104 women). All the CHD patients enrolled in our study were diagnosed through angiography. Clinical and angiographic data of CHD patients were collected. After stratification on age and sex of the patients, logistic analysis method was used to evaluate the prevalence rates on conventional risk factors and to analyze the features of coronary lesions on CHD. RESULTS: (1) More than two risk factors and advancing age of onset were commonly seen in female CHD patients. In those premature female CHD patients (age<45 years), there was a high proportion the habit of smoking. With the increase of age, proportions of patients with diabetes mellitus and hyperlipidemia also significantly increased. For male patients at different age, the proportions of smoking were high. (2) Data from logistic analysis suggested that diabetes mellitus could increase the prevalence of CHD on women (OR=2.05, 95%CI: 1.49-2.81, P<0.001), and smoking was a risk factor for men (OR=9.27, 95%CI: 7.68-11.19, P<0.001). (3) Along with the increase of age, female patients appeared to have more coronary vessel injures or severe coronary artery lesions. Different from the females, there was no change could seen on the characteristics of coronary lesions at different age for males. CONCLUSION: Prevalence rates on risk factors and the characteristics of coronary lesions appeared to be different with age. Diabetes mellitus and hyperlipidemia seemed to impact more on women while smoking seemed to impact more on men. PMID- 22781420 TI - [Blood lactic acid level and APACHE II score on prognosis of critically ill elderly patients]. AB - OBJECTIVE: To analyze the relevance between blood lactic acid level and acute physiology and chronic health evaluation II (APACHE II) score in order to provide guideline for clinical treatment. METHODS: Retrospective analyses on 537 critically ill elderly patients who were hospitalized in the ICU with their blood lactic acid level tested and APACHE II scores calculated. RESULTS: The overall death rate was 35.75% (192/537) with the APACHE II score as (22.6+/-12.8), and blood lactic acid level as (6.84+/-2.01) mmol/L. The blood lactic acid level among deaths was obviously higher than in the control group, with significant differences (P<0.05). The level of blood lactic acid was positively related to APACHE II score (r=0.572, P<0.05) while the death rate was both positively related to APACHE II score (r=0.475, P<0.05) and the level of blood lactic acid (r=0.506, P<0.05). CONCLUSION: There seemed a positive correlation between blood lactic acid level and the APACHE II score. Both of them showed good relevance with the prognosis of the disease. PMID- 22781421 TI - [Design and implementation of Geographical Information System on prevention and control of cholera]. AB - To build the Geographical Information System (GIS) database for prevention and control of cholera programs as well as using management analysis and function demonstration to show the spatial attribute of cholera. Data from case reporting system regarding diarrhoea, vibrio cholerae, serotypes of vibrio cholerae at the surveillance spots and seafoods, as well as surveillance data on ambient environment and climate were collected. All the data were imported to system database to show the incidence of vibrio cholerae in different provinces, regions and counties to support the spatial analysis through the spatial analysis of GIS. The epidemic trends of cholera, seasonal characteristics of the cholera and the variation of the vibrio cholerae with times were better understood. Information on hotspots, regions and time of epidemics was collected, and helpful in providing risk prediction on the incidence of vibrio cholerae. The exploitation of the software can predict and simulate the spatio-temporal risks, so as to provide guidance for the prevention and control of the disease. PMID- 22781422 TI - [Application of log-linear model in the case-parent triad study]. AB - We were introducing a log-linear model for case-parent triad study. Data from a previous study of the association between MTHFR C677T and cleft lip with or without cleft palate (CL/P) was analyzed, in order to investigate the maternal effect, fetal effect and their interaction, using a series of log-linear models. Our results showed that mothers who were carrying two copies of MTHFR C677T variant alleles appeared to have reduced the risk of CL/P in offspring, comparing to those with homozygous of wild-type allele. With S2=0.43 (95%CI: 0.19-0.95). No significant association was found for fetal genotype and maternal-fetal interaction with CL/P. Log-linear model method seemed to be useful in the estimation of maternal effect, fetal effect and maternal-fetal interaction, in the case-parent triad study design. This approach showed specific benefit in studies that related to genetic effects on complex diseases such as pregnancy complications and diseases originated from fetus. PMID- 22781423 TI - ["Group" and organization: a dimension of collaboration of anthropology and epidemiology]. AB - "Group" is a key concept in epidemiological research and "organization" is a core concept in anthropology. Group takes focus on the specific characteristics of the subjects, while organization takes focus on the relationship between the objects. For the characteristics and relationship of the objects that interacting with each other, the two concepts could be complementary in specific studies, and this will be the basic dimension of Interdisciplinary collaboration of anthropology and epidemiology. PMID- 22781424 TI - Effect of QRS duration and morphology on cardiac resynchronization therapy outcomes in mild heart failure: results from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. We aimed to assess the impact of baseline QRS duration and morphology and the change in QRS duration with pacing on CRT outcomes in mild heart failure. METHODS AND RESULTS: Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) was a multicenter randomized trial of CRT among 610 patients with mild heart failure. Baseline and CRT-paced QRS durations and baseline QRS morphology were evaluated by blinded core laboratories. The mean baseline QRS duration was 151+/-23 milliseconds, and 60.5% of subjects had left bundle-branch block (LBBB). Patients with LBBB experienced a 25.3-mL/m(2) mean reduction in left ventricular end-systolic volume index (P<0.0001), whereas non-LBBB patients had smaller decreases (6.7 mL/m(2); P=0.18). Baseline QRS duration was also a strong predictor of change in left ventricular end-systolic volume index with monotonic increases as QRS duration prolonged. Similarly, the clinical composite score improved with CRT for LBBB subjects (odds ratio, 0.530; P=0.0034) but not for non-LBBB subjects (odds ratio, 0.724; P=0.21). The association between clinical composite score and QRS duration was highly significant (odds ratio, 0.831 for each 10-millisecond increase in QRS duration; P<0.0001), with improved response at longer QRS durations. The change in QRS duration with CRT pacing was not an independent predictor of any outcomes after correction for baseline variables. CONCLUSION: REVERSE demonstrated that LBBB and QRS prolongation are markers of reverse remodeling and clinical benefit with CRT in mild heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271154. PMID- 22781425 TI - The prognostic significance of premature ventricular complexes in adults without clinically apparent heart disease: a meta-analysis and systematic review. AB - AIMS: Meta-analysis and systematic review to determine the long-term prognostic significance of premature ventricular complexes (PVCs) in adults without clinically apparent heart disease. METHODS: Relevant studies were searched on MEDLINE and EMBASE. INCLUSION CRITERIA: controlled studies on adults without clinically apparent heart disease comparing the prognosis of the presence against the absence of PVCs. ENDPOINTS: all-cause mortality, cardiovascular mortality, sudden cardiac death or development of ischaemic heart disease. OR of endpoints were analysed with random effects model. Relationships between study outcomes and study characteristics were assessed by meta-regression and sensitivity analysis. RESULTS: Eight studies satisfied the inclusion criteria. Meta-analysis shows that in adults without clinically apparent heart disease, PVCs on ECG recording are associated with a pooled OR of 1.72 (95% CI 1.28 to 2.31) of endpoints compared with those without PVCs. However, only one study used echocardiogram or stress test to rule out heart disease. Meta-regression identified mean sample age (p=0.001), diabetes (p=0.005) and hypertension (p=0.005) as predictors of events. Only studies that used 100% male, not 100% female or mixed gender, found increased events. CONCLUSIONS: Most studies on PVC prognosis in 'normal hearts' did not use advanced tests to rule out structural heart disease. Among these patients, PVCs are associated with a worse cardiovascular outcome if patients are older and have higher cardiovascular risk, suggesting that the poor prognosis studies may have inadvertently included patients with occult structural heart disease, the population in which PVCs are known to confer adverse outcomes. PMID- 22781426 TI - Body mass index, blood pressure, and risk of depression in the elderly: a marginal structural model. AB - The authors' objective was to investigate the associations of body mass index (BMI; weight (kg)/height (m)(2)) and blood pressure with the risk of developing depression in a large sample of elderly French participants (aged >=65 years) followed for 10 years (Dijon portion of the Three-City Study, 1999-2010). Depression was defined as either having major depressive symptoms according to the Mini-International Neuropsychiatric Interview or taking antidepressant medication. The authors fitted marginal structural models to examine the relations of BMI and blood pressure with depression. Among subjects who were depression-free at baseline (n = 3,090), 478 developed incident depression over 10 years of follow-up. The analyses showed that after baseline values and time dependent confounders were controlled, subjects with high BMI at follow-up had an increased adjusted risk of developing depression compared with subjects with normal BMI (risk ratio = 1.60, 95% confidence interval: 1.03, 2.51). Compared with subjects with normal blood pressure, those with high blood pressure were not at increased risk of incident depression, whereas those with low blood pressure had a higher risk of developing depression. These findings provide some epidemiologic support for implication of lifestyle risk factors in the development of depression in the elderly. Future studies should focus on evaluating lifestyle and obesity interventions among the elderly. PMID- 22781427 TI - A simple unified approach for estimating natural direct and indirect effects. AB - An important problem within both epidemiology and many social sciences is to break down the effect of a given treatment into different causal pathways and to quantify the importance of each pathway. Formal mediation analysis based on counterfactuals is a key tool when addressing this problem. During the last decade, the theoretical framework for mediation analysis has been greatly extended to enable the use of arbitrary statistical models for outcome and mediator. However, the researcher attempting to use these techniques in practice will often find implementation a daunting task, as it tends to require special statistical programming. In this paper, the authors introduce a simple procedure based on marginal structural models that directly parameterize the natural direct and indirect effects of interest. It tends to produce more parsimonious results than current techniques, greatly simplifies testing for the presence of a direct or an indirect effect, and has the advantage that it can be conducted in standard software. However, its simplicity comes at the price of relying on correct specification of models for the distribution of mediator (and exposure) and accepting some loss of precision compared with more complex methods. Web Appendixes 1 and 2, which are posted on the Journal's Web site (http://aje.oupjournals.org/), contain implementation examples in SAS software (SAS Institute, Inc., Cary, North Carolina) and R language (R Foundation for Statistical Computing, Vienna, Austria). PMID- 22781429 TI - Outsourcing clinical trials. PMID- 22781428 TI - Dietary fatty acid intake and prostate cancer survival in Orebro County, Sweden. AB - Although dietary fat has been associated with prostate cancer risk, the association between specific fatty acids and prostate cancer survival remains unclear. Dietary intake of 14 fatty acids was analyzed in a population-based cohort of 525 Swedish men with prostate cancer in Orebro County (1989-1994). Multivariable hazard ratios and 95% confidence intervals for time to prostate cancer death by quartile and per standard deviation increase in intake were estimated by Cox proportional hazards regression. Additional models examined the association by stage at diagnosis (localized: T0-T2/M0; advanced: T0-T4/M1, T3 T4/M0). Among all men, those with the highest omega-3 docosahexaenoic acid and total marine fatty acid intakes were 40% less likely to die from prostate cancer (P(trend) = 0.05 and 0.04, respectively). Among men with localized prostate cancer, hazard ratios of 2.07 (95% confidence interval: 0.93, 4.59; P(trend) = 0.03) for elevated total fat, 2.39 (95% confidence interval: 1.06, 5.38) for saturated myristic acid, and 2.88 (95% confidence interval: 1.24, 6.67) for shorter chain (C4-C10) fatty acid intakes demonstrated increased risk for disease specific mortality for the highest quartile compared with the lowest quartile. This study suggests that high intake of total fat and certain saturated fatty acids may worsen prostate cancer survival, particularly among men with localized disease. In contrast, high marine omega-3 fatty acid intake may improve disease specific survival for all men. PMID- 22781431 TI - Researchers hope new database becomes universal cancer genomics tool. PMID- 22781432 TI - Study supports PSA velocity risk count. PMID- 22781433 TI - Illuminating the diabetes-cancer link. PMID- 22781434 TI - Association between germline HOXB13 G84E mutation and risk of prostate cancer. AB - Recently, a G84E mutation in HOXB13, a gene involved in prostate development, was shown to be strongly associated with an increased risk of prostate cancer. To confirm this association in a screening setting, we conducted a case-control study and sequenced germline DNA from peripheral leukocytes of 1843 men diagnosed with prostate cancer (case subjects) and 2225 men without prostate cancer (control subjects) for mutations in HOXB13. Subjects (aged 40-94 years) were prescreened and underwent a prostate biopsy at two tertiary care centers in Canada. The frequency of HOXB13 variants was determined in case subjects and control subjects by race, and odds ratios and 95% confidence intervals were based on 2*2 table analysis. All statistical tests were two-sided. Twelve men of white race were identified to be carriers of the G84E mutation. The G84E mutation was more frequent among white case subjects than among white control subjects (10 of 1525 [0.7%] vs 2 of 1757 [0.1%], P = .01) and was associated with an increased risk of prostate cancer (unadjusted odds ratio = 5.8, 95% confidence interval = 1.3 to 26.5, P = .01). PMID- 22781435 TI - The role of cancer research in noncommunicable disease control. AB - Noncommunicable diseases were estimated to claim more than 36 million lives worldwide in 2008. Major contributors to this burden were cardiovascular disease, cancer, chronic respiratory diseases, and diabetes. The United Nations General Assembly held a high-level meeting on noncommunicable diseases in September 2011 for heads of states and governments, conscious of the projected increases in disease incidence, particularly in low- and middle-income countries. This meeting followed the Special Session on HIV/AIDS in 2001, the only other high-level meeting to discuss a health topic and orient the global political agenda toward a growing threat to human development. Proposed strategies for control of noncommunicable diseases focused mainly on the shared risk factors of tobacco, harmful use of alcohol, physical inactivity, and unhealthy diet. However, for cancer, a broader response is required. Notably, the heterogeneity of cancer with respect to its geographical distribution, etiology, and pathology all demand a more nuanced, regional, or even local approach. Preparations for the meeting elicited enormous attention from governments and nongovernmental organizations, but the engagement of the research community was less evident. This commentary calls for the involvement of the cancer research community in response to the further action detailed in the United Nations Political Declaration emanating from the meeting, identifies a number of cancer-specific priorities, including vaccination against hepatitis B virus and human papillomavirus, cervical cancer screening, and early detection of breast cancer, and suggests areas where cancer research can provide the evidence base for cancer control, notably in improving the quality and coverage of cancer registration, elucidating cancer etiology, and evaluating interventions, including their implementation in low-resource health care settings. Finally, the need for global cooperation in developing a research agenda for low- and middle-income countries is highlighted. PMID- 22781436 TI - Comparison of four probabilistic models (CARES((r)), CalendexTM, ConsExpo, and SHEDS) to estimate aggregate residential exposures to pesticides. AB - Two deterministic models (US EPA's Office of Pesticide Programs Residential Standard Operating Procedures (OPP Residential SOPs) and Draft Protocol for Measuring Children's Non-Occupational Exposure to Pesticides by all Relevant Pathways (Draft Protocol)) and four probabilistic models (CARES((r)), CalendexTM, ConsExpo, and SHEDS) were used to estimate aggregate residential exposures to pesticides. The route-specific exposure estimates for young children (2-5 years) generated by each model were compared to evaluate data inputs, algorithms, and underlying assumptions. Three indoor exposure scenarios were considered: crack and crevice, fogger, and flying insect killer. Dermal exposure estimates from the OPP Residential SOPs and the Draft Protocol were 4.75 and 2.37 mg/kg/day (crack and crevice scenario) and 0.73 and 0.36 mg/kg/day (fogger), respectively. The dermal exposure estimates (99th percentile) for the crack and crevice scenario were 16.52, 12.82, 3.57, and 3.30 mg/kg/day for CARES, Calendex, SHEDS, and ConsExpo, respectively. Dermal exposure estimates for the fogger scenario from CARES and Calendex (1.50 and 1.47 mg/kg/day, respectively) were slightly higher than those from SHEDS and ConsExpo (0.74 and 0.55 mg/kg/day, respectively). The ConsExpo derived non-dietary ingestion estimates (99th percentile) under these two scenarios were higher than those from SHEDS, CARES, and Calendex. All models produced extremely low exposure estimates for the flying insect killer scenario. Using similar data inputs, the model estimates by route for these scenarios were consistent and comparable. Most of the models predicted exposures within a factor of 5 at the 50th and 99th percentiles. The differences identified are explained by activity assumptions, input distributions, and exposure algorithms. PMID- 22781437 TI - Applying the maximum cumulative ratio methodology to biomonitoring data on dioxin like compounds in the general public and two occupationally exposed populations. AB - Maximum cumulative ratio (MCR) is a person's cumulative exposure to multiple chemicals divided by the maximum chemical-specific exposure where exposure is expressed on a toxicologically equivalent basis. It is a tool for assessing the need for performing cumulative exposure assessments. In this paper, MCR values were calculated for the three groups of individuals with biomonitoring data of 26 dioxin-like compounds (DLCs) based on the World Health Organization toxic equivalent factors (TEFs). Although the two occupational groups have higher total toxicity equivalence (TEQ) levels than the NHANES group, average MCR values of the three groups are similar (3.5, 3.6, and 3.2). These MCR values are higher than those seen in our earlier studies, supporting the practice of performing cumulative assessments for DLCs. The MCR values also indicate that only 2-5 of the 26 chemicals make significant contributions to total TEQ values. Interestingly, MCR is negatively correlated with total TEQ (in all the three groups) and age (in the NHANES group). Additionally, MCR is lower in workers where occupational exposures are larger than background exposures. Although overall exposure is the first factor to consider in any mixtures assessment, this paper confirms the usefulness of MCR as a tool for analyzing the pattern of chemical-specific contributions to the total exposure levels of mixtures based on biomonitoring data when TEFs or similar approaches are available. PMID- 22781438 TI - Organophosphorous pesticide breakdown products in house dust and children's urine. AB - Human exposure to preformed dialkylphosphates (DAPs) in food or the environment may affect the reliability of DAP urinary metabolites as biomarkers of organophosphate (OP) pesticide exposure. We conducted a study to investigate the presence of DAPs in indoor residential environments and their association with children's urinary DAP levels. We collected dust samples from homes in farmworker and urban communities (40 homes total, n=79 samples) and up to two urine samples from resident children ages 3-6 years. We measured six DAPs in all samples and eight DAP-devolving OP pesticides in a subset of dust samples (n=54). DAPs were detected in dust with diethylphosphate (DEP) being the most frequently detected (>=60%); detection frequencies for other DAPs were <=50%. DEP dust concentrations did not significantly differ between communities, nor were concentrations significantly correlated with concentrations of chlorpyrifos and diazinon, the most frequently detected diethyl-OP pesticides (Spearman rho=-0.41 to 0.38, P>0.05). Detection of DEP, chlorpyrifos, or diazinon, was not associated with DEP and/or DEP+diethylthiophosphate detection in urine (Kappa coefficients=-0.33 to 0.16). Finally, estimated non-dietary ingestion intake from DEP in dust was found to be <=5% of the dose calculated from DEP levels in urine, suggesting that ingestion of dust is not a significant source of DAPs in urine if they are excreted unchanged. PMID- 22781439 TI - Antioxidant activity of new aramide nanoparticles containing redox-active N phthaloyl valine moieties in the hepatic cytochrome P450 system in male rats. AB - We report the synthesis of aramide nanoparticles containing a chiral N-phthaloyl valine moiety and their antioxidant activities on hepatic contents of cytochrome P450, amidopyrene N-demethylase, aniline-4-hyroxylase and induced the hepatic content of cytochrome b5 and nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome C-reductase. Polymers were obtained as well-separated spherical nanoparticles while highly aggregated particles via H-bonding organization of the aramide-containing pyridine led to a thin layer formation. The effects of the nanoparticles and CCl4 on enzyme activities and thiobarbituric acid reactive substances (TBARS) levels of male rat liver were studied. Pretreatments of rats with the polyamides prior to the administration of CCl4 decreased the hepatic content of the tested enzymes. Doses reduced the toxic effects exerted by (*CCl3) upon the liver through inhibition of the cytochrome P450 system. Inhibition of such metabolizing enzymes could reduce the carcinogenic effects of chemical carcinogens. PMID- 22781440 TI - Preparative isolation and purification of four compounds from Cistanches deserticola Y.C. Ma by high-speed counter-current chromatography. AB - Following a constituent enrichment step on a silica gel column, four phenyl ethanoid glycosides were successfully isolated from Cistanches deserticola and purified by preparative high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of ethyl acetate-n-butanol-ethanol-water (40:6:6:50, v/v/v/v). A total of 30.9 mg acteoside, 13.0 mg isoacteoside, 12.5 mg syringalide A 3'-alpha-L-rhamnopyranoside and 7.2 mg 2'-acetylacteoside with purity of higher than 95%, as determined by HPLC-ELSD, were obtained in one-step separation from 297 mg of Cistanche deserticola extract, respectively. Their structures were identified by HR-MS, 1H-NMR and 13C-NMR. PMID- 22781441 TI - New trifluoromethyl triazolopyrimidines as anti-Plasmodium falciparum agents. AB - According to the World Health Organization, half of the World's population, approximately 3.3 billion people, is at risk for developing malaria. Nearly 700,000 deaths each year are associated with the disease. Control of the disease in humans still relies on chemotherapy. Drug resistance is a limiting factor, and the search for new drugs is important. We have designed and synthesized new 2 (trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine derivatives based on bioisosteric replacement of functional groups on the anti-malarial compounds mefloquine and amodiaquine. This approach enabled us to investigate the impact of: (i) ring bioisosteric replacement; (ii) a CF3 group substituted at the 2 position of the [1,2,4]triazolo[1,5-a]pyrimidine scaffold and (iii) a range of amines as substituents at the 7-position of the of heterocyclic ring; on in vitro activity against Plasmodium falciparum. P. falciparum dihydroorotate dehydrogenase (PfDHODH) through strong hydrogen bonds. The presence of a trifluoromethyl group at the 2-position of the [1,2,4]triazolo[1,5-a]pyrimidine ring led to increased drug activity. Thirteen compounds were found to be active, with IC50 values ranging from 0.023 to 20 MUM in the anti-HRP2 and hypoxanthine assays. The selectivity index (SI) of the most active derivatives 5, 8, 11 and 16 was found to vary from 1,003 to 18,478. PMID- 22781442 TI - Phylattrin, a new cytotoxic xanthone from Calophyllum soulattri. AB - Our continuing studies on secondary metabolites from the stem bark of Calophyllum soulattri has led to the isolation of another new diprenylated xanthone, phylattrin (1), in addition to five other xanthones and two common sterols. The xanthones are soulattrin (2), caloxanthone C (3), macluraxanthone (4), brasixanthone B (5) and trapezifolixanthone (6) while the sterols are stigmasterol (7) and beta-sitosterol (8). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D-NMR, HRESIMS, IR and UV. Compounds 1-7 exhibited moderate cytotoxic activities against SNU-1, HeLa, Hep G2, NCI-H23, K562, Raji, LS174T, IMR-32 and SK-MEL-28 cells. PMID- 22781443 TI - From BACE1 inhibitor to multifunctionality of tryptoline and tryptamine triazole derivatives for Alzheimer's disease. AB - Efforts to discover new drugs for Alzheimer's disease emphasizing multiple targets was conducted seeking to inhibit amyloid oligomer formation and to prevent radical formation. The tryptoline and tryptamine cores of BACE1 inhibitors previously identified by virtual screening were modified in silico for additional modes of action. These core structures were readily linked to different side chains using 1,2,3-triazole rings as bridges by copper catalyzed azide-alkyne cycloaddition reactions. Three compounds among the sixteen designed compounds exerted multifunctional activities including beta-secretase inhibitory action, anti-amyloid aggregation, metal chelating and antioxidant effects at micromolar levels. The neuroprotective effects of the multifunctional compounds 6h, 12c and 12h on Abeta1-42 induced neuronal cell death at 1 MUM were significantly greater than those of the potent single target compound, BACE1 inhibitor IV and were comparable to curcumin. The observed synergistic effect resulting from the reduction of the Abeta1-42 neurotoxicity cascade substantiates the validity of our multifunctional strategy in drug discovery for Alzheimer's disease. PMID- 22781444 TI - Moringa oleifera hydroethanolic extracts effectively alleviate acetaminophen induced hepatotoxicity in experimental rats through their antioxidant nature. AB - The aim of the study was to investigate the in vitro antioxidant properties Moringa oleifera Lam. (MO) extracts and its curative role in acetaminophen (APAP) induced toxic liver injury in rats caused by oxidative damage. The total phenolic content and antioxidant properties of hydroethanolic extracts of different MO edible parts were investigated by employing an established in vitro biological assay. In the antihepatotoxic study, either flowers or leaves extract (200 mg/kg or 400 mg/kg, i.p) were administered an hour after APAP administration, respectively. N-Acetylcysteine was used as the positive control against APAP induced hepatotoxicity. The levels of liver markers such as alanine aminotransferase (ALT) and the levels of oxidative damage markers including malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) protein adduct, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were analysed and compared between experimental groups. Among MO edible parts the flower extracts contain the highest total phenolic content and antioxidant capacity, followed by leaves extract. The oxidative marker MDA, as well as 4-HNE protein adduct levels were elevated and GSH, SOD and CAT were significantly decreased in groups treated with hepatotoxin. The biochemical liver tissue oxidative markers measured in the rats treated with MO flowers and leaves hydroethanolic extracts showed a significant (p < 0.05) reduction in the severity of the liver damage. The results of this study strongly indicate the therapeutic properties of MO hydroethanolic extracts against acute liver injury and thereby scientifically support its traditional use. PMID- 22781447 TI - Dibenz[a,c]anthracene derivatives exhibiting columnar mesophases over broad temperature ranges. AB - We report the synthesis and characterization of a series of novel hexaalkoxydibenz[a,c]anthracenes. While the parent compound is not mesomorphic, the introduction of substituents in the 10- and 13-positions yields compounds with columnar liquid crystalline phases over very broad temperature ranges. PMID- 22781446 TI - A silica nanoparticle-based sensor for selective fluorescent detection of homocysteine via interaction differences between thiols and particle-surface bound polymers. AB - Biothiols play crucial roles in maintaining biological systems; among them, homocysteine (Hcy) has received increasing attention since elevated levels of Hcy have been implicated as an independent risk factor for cardiovascular disease. Hence, the selective detection of this specific biothiol, which is a disease associated biomarker, is very important. In this paper, we demonstrate a new mesoporous silica nanoparticle-based sensor for selective detection of homocysteine from biothiols and other common amino acids. In this fluorescent sensing system, an anthracene nitroolefin compound was placed inside the mesopores of mesoporous silica nanoparticles (MSNs) and used as a probe for thiols. The hydrophilic polyethylene glycol (PEG 5000) molecules were covalently bound to the MSN surface and used as a selective barrier for Hcy detection via different interactions between biothiols and the PEG polymer chains. The sensor can discriminate Hcy from the two low-molecular mass biothiols (GSH and Cys) and other common amino acids in totally aqueous media as well as in serum, with a detection limit of 0.1 MUM. This strategy may offer an approach for designing other MSN-based sensing systems by using polymers as diffusion regulators in sensing assays for other analytes. PMID- 22781445 TI - Electrospray ionization mass spectrometric analysis of highly reactive glycosyl halides. AB - Highly reactive glycosyl chlorides and bromides have been analysed by a routine mass spectrometric method using electrospray ionization and lithium salt adduct forming agents in anhydrous acetonitrile solution, providing salient lithiated molecular ions [M+Li]+, [2M+Li]+ etc. The role of other adduct-forming salts has also been evaluated. The lithium salt method is useful for accurate mass determination of these highly sensitive compounds. PMID- 22781448 TI - [New viewpoint in thyroid disease treatment]. PMID- 22781449 TI - [Thyroid disease: new challenge for Chinese public health care]. PMID- 22781450 TI - [Association analysis of PDE8B gene polymorphisms with the susceptibility to Hyperthyroxinemia in Chinese Han population]. AB - OBJECTIVE: To explore the correlations of the polymorphisms of phosphodiesterase 8B (PDE8B) gene with Hyperthyroxinemia in Chinese Han population. METHODS: A case control study of genotype 657366 SNPs was performed by Illumina Human660-Quad BeadChips in 98 Hyperthyroxinemia patients and 1300 controls. And 25 SNPs within PDE8B gene intron 1 were used for association analyses. RESULTS: Allele frequencies of 5 SNPS in PDE8B gene intron 1 showed significant differences between the case and control groups (P < 0.05). In comparison with the control group, the genotypic distributions of rs7714529 (chi(2) = 6.430, P = 0.040), rs12514694 (chi(2) = 7.191, P = 0.027) and rs10066802 (chi(2) = 9.213, P = 0.010) in H-TSH group had significant differences. Haplotype AGTAG (rs7702192/rs7714529/rs251421/rs12514694/rs10066802) was over-represented in hyperthyrotropinemia cases versus the control group. CONCLUSION: PDE8B gene polymorphisms may be correlated with Hyperthyroxinemia in Chinese Han population. And it may provide new concepts for the treatment of thyroid dysfunction. PMID- 22781451 TI - [Isolation, proliferation and differentiation of thyroid stem cell from human thyroid nodule tissue]. AB - OBJECTIVE: To explore the presence of a characteristic stem cell population (side population, SP) in human thyroid gland and perform sphere culture method for the isolation and proliferation of thyroid stem cell. METHODS: Flow cytometry and cell sorting were performed to identify and isolate the ABCG2-positive SP cells from primary thyroid cells. The comparison of gene profiles and morphology between SP and main population (MP) were performed. Primary thyroid cells were also cultured in neurosphere-like growth condition for sphere formation. Gene profile of developed spheres was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and thyroid lineage commitment was then induced in a differentiating condition. In stem cell-derived thyrocytes, embedded in collagen to form follicles, TSH-dependent (125)iodide uptake was measured. RESULTS: The SP was identified as a population enriched in stem cells with typical morphology, and characteristics of self-renewal and differentiation. Nonadherent clonal spheres developed in thyroid cell cultures, displaying an expression pattern resembling that of SP cells and in response to TSH and serum these sphere cells differentiated into thyrocytes expressing PAX8, thyroglobulin, sodium iodide symporter, thyroid-stimulating hormone receptor and thyroperoxidase mRNA. And there was TSH-dependent (125)iodide uptake. CONCLUSION: It is shown first time that human thyroid contains an undescribed population of cells with SP phenotype and clonal expansion capacity. Moreover sphere culture method is developed for the isolation and proliferation of thyroid stem cell. PMID- 22781452 TI - [Influences of nevirapine on cell proliferation and expression of sodium/iodide symporter in human anaplastic thyroid carcinoma cell line]. AB - OBJECTIVE: To explore the effects of nevirapine on the proliferation and expression of sodium-iodide symporter (NIS) mRNA in FRO cells in vitro. METHODS: The cells were incubated in different concentrations of nevirapine to evaluate the cell growth rate. And the expressions of NIS mRNA and TSHR mRNA were determined by real-time quantitative reverse polymerase chain reaction. RESULTS: Cell proliferation was inhibited after a 96 h nevirapine treatment. After incubating in the presence of 200 and 350 umol/L nevirapine, the expression of NIS mRNA was (1.39 +/- 0.04) and (1.85 +/- 0.28) times versus the control cells (P < 0.01) while the expressions of TSHR mRNA was (2.23 +/- 1.47) and (2.83 +/- 0.78) times versus the control cells respectively (both P < 0.05). CONCLUSION: Nevirapine inhibits cell proliferation in FRO cell line. More importantly, the cells exposed to nevirapine may induce the up-regulations of NIS mRNA and TSHR mRNA. PMID- 22781453 TI - [Relationship between glycated albumin level and pancreatic beta cell function in newly diagnosed type 2 diabetics]. AB - OBJECTIVE: To explore the relationship between glycated albumin (GA) level and pancreatic beta cell function in newly diagnosed type 2 diabetics. METHODS: The subjects sought the confirmation of diabetes diagnosis or underwent diabetes screening tests in high-risk patients from January 2008 to October 2010. All of them underwent 75 g oral glucose tolerance test (OGTT) and insulin releasing test. The levels of GA and hemoglobin A1c (HbA1c) were analyzed by liquid enzymatic method and high performance liquid chromatography respectively. Homeostasis model assessment (HOMA) was used to evaluate the basal insulin resistance (HOMA-IR) and pancreatic beta cell function (HOMA-beta). DeltaI30/DeltaG30 was used to evaluate early-phase insulin secretion after a glucose load. RESULTS: (1) Among 500 type 2 diabetics according to the diagnostic criteria of WHO (1999), 279 were males and 221 were females. Average age was 56.3 +/- 12.3, GA (21.1 +/- 5.4)% and HbA1c (7.0 +/- 1.3)%. (2) A significantly positive relationship was shown between HbA1c and GA (r = 0.691, P < 0.01). GA was also positively correlated with fasting plasma glucose (FPG), 0.5 hPG, 1 hPG, 2 hPG and 3 hPG after a glucose load of OGTT test (r = 0.511 - 0.627, P < 0.01). (3) GA was negatively correlated with body mass index (BMI) (r = -0.112, P < 0.01), HOMA-beta (r = -0.350, P < 0.01) and DeltaI30/DeltaG30 (r = -0.263, P < 0.01). (4) Multivariant stepwise regression analysis showed that HbA1c, FPG, 3 hPG and DeltaI30/DeltaG30 were independent factors of GA level. CONCLUSION: Glycated albumin level is closely correlated with the function of early-phase insulin secretion in newly diagnosed type 2 diabetics. PMID- 22781454 TI - [Post-therapeutic change of cathelicidin LL-37 in asthmatics of different inflammatory phenotypes]. AB - OBJECTIVE: To explore the post-therapeutic change of cathelicidin LL-37 in asthmatics of different inflammatory phenotypes. METHODS: Thirty-four patients with initially diagnosed asthma (asthma group) and 14 normal subjects (control group) were recruited at Nanfang Hospital from August 2009 to August 2010 for this prospective study. Sputum and venous blood samples were collected and analyzed for cell differential. Eosinophilic asthma was defined as the count of sputum eosinophils >= 3%. The LL-37 concentrations in plasma and sputum supernatant were measured by enzyme-linked immunosorbent assay (ELISA) kit. The subjects were treated with budesonide/formoterol (160/4.5 ug) one inhalation twice daily and re-examined after 1 month. RESULTS: Prior to treatment, there were no differences between the asthma and control groups in the levels of LL-37 in plasma and sputum supernatant (P = 0.427,0.427). The plasma concentrations of LL-37 in asthma group were negatively correlated with baseline forced expiratory volume in one second (FEV(1), r = -0.470, P = 0.005), percent predicted of FEV(1) (FEV(1)%pred, r = -0.421, P = 0.013) and forced vital capacity (FVC, r = -0.367, P = 0.033). After treatment, the plasma and sputum supernatant concentrations of LL-37 (M (Q(R))) in the asthma group (5.6 (16.2), 65.6 (184.0) ug/L) were significantly higher than those baseline concentrations (5.03 (9.21), 28.40(109.76) ug/L, P = 0.005, 0.015). In the eosinophilic asthma subgroup, the plasma and sputum supernatant concentrations of LL-37 (M (Q(R))) after treatment (5.3 (19.3), 65.6 (185.2) ug/L) were significantly higher than those baseline concentrations (6.7 (8.9) L, 35.3 (102.0) ug/L, P = 0.021,0.014). And in the non eosinophilic asthma subgroup, the changes of plasma and sputum supernatant concentrations of LL-37 showed no significant differences (P = 0.139, 0.386). In the asthma group, the correlations between plasma concentrations of LL-37 and FEV(1), FEV(1)%pred, FVC were not statistically significant (P = 0.283, 0.706,0.272) after treatment. CONCLUSIONS: LL-37 may participate in the aggravation of asthma. The elevated concentrations of LL-37 in eosinophilic asthma is probably due to the resolved suppression of LL-37 expression by eosinophilic inflammation. But its mechanism needs further researches. PMID- 22781455 TI - [Quantitative real-time polymerase chain reaction for the diagnosis of invasive fungal disease]. AB - OBJECTIVE: To establish the diagnostic assays of quantitative real-time polymerase chain reaction (PCR) for the diagnosis of invasive fungal disease and evaluate their accuracy in clinical samples. METHODS: Three assays have been developed for the diagnosis of clinically prevalent fungi, Aspergillus spp. and Candida spp.. Their analytical sensitivity and specificity were evaluated. Twenty one serum samples from invasive fungal disease patients and non-invasive fungal disease patients were analyzed by the diagnostic assays and the accuracy was evaluated. RESULTS: Three assays were managed to run at the same condition. The universal fungi assay was able to detect, but not differentiate between most of the pathogenic fungi, including A. fumigatus, A. flavus, A. niger, C. albicans, C. parapsilosis, C. tropicalis, C.kruseii, C.glabrata, Cryptococcus neoformans, Rhizomucor variabilis, Rhizopus arrhizus and Penicillosis marneffei. The assays of Aspergillus spp. and Candida spp. were able to detect, but not differentiate between A. fumigatus, A. flavus, A. niger and C. albicans, C. parapsilosis, C. tropicalis. The detection limits of assays were 4 pg of A. fumigatus gDNA, 2 copies of A. fumigatus and 2 copies of C. albicans respectively. The results of quantitative real-time PCR matched well with each other and were identical to the classical procedures in all patients. Among the 11 patients with invasive fungal disease, the pathogens were identified down to a genus level in 2 invasive aspergillosis patients and 2 invasive candidiasis patients. And the other 7 patients could be diagnosed with invasive fungal disease by the universal fungi assay. All the 10 serum samples from non-invasive fungal disease patients were revealed as negative. CONCLUSION: The universal fungi assay is helpful in screening while the assays of Aspergillus spp. and the Candida spp. may identify the pathogens down to a genus level. PMID- 22781456 TI - [Applied studies of structured triglycerides for parenteral nutrition in severe hemorrhagic shock patients after resuscitation]. AB - OBJECTIVE: To evaluate the effects of structured triglycerides in parenteral nutrition versus a physical medium-chain triglycerides (MCT)/long-chain triglycerides (LCT) mixture on severe hemorrhagic shock patients after resuscitation. METHODS: In a randomized trial, we studied 20 critical patients with a total blood loss of over 3000 ml perioperatively and/or intraoperatively. The use of triglycerides started from Day 3 postoperation and parenteral nutrition lasted for no less than 5 days. They were allocated to receive one of two nutrition regiments: structured triglycerides in Group A (n = 10) and MCT/LCT in Group B (n = 10). There were no significant differences of general conditions in two groups. Before the start of parenteral nutrition (d0), d1 d3 and d5 after start of infusion, the following parameters were measured: hemoglobin (Hb), platelet count (Plt), alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), serum triglycerides (TG), prealbumin (PA) and transferrin (TF). And mean artery pressure (MAP), heart rate (HR) and central vein pressure (CVP) were also recorded at the same time-points. Then the post-TG changes of the above data were compared in both groups. RESULTS: After the use of triglycerides, there were no significant differences of MAP, HR, CVP, Hb and Plt in both groups (P > 0.05). At D3 and D5, the serum levels of TG ((2.1 +/- 0.4) vs (1.6 +/- 0.6) mg/L, (2.3 +/- 0.7) vs (1.5 +/- 0.3) mg/L) and alanine aminotransferase ((133 +/- 58) vs (97 +/- 26) U/L; (116 +/- 48) vs (77 +/- 31) U/L) were significantly higher in Group B versus those receiving structured triglycerides in Group A (P < 0.05). TB ((18 +/- 15) vs (18 +/- 11) umol/L) and DB ((8.9 +/- 3.2) vs (8.8 +/- 2.5) umol/L) had no significant differences in two groups (P > 0.05). The serum levels of such nutrition markers as PA ((195 +/- 55) vs (166 +/- 55) mg/L,(245 +/ 53) vs (195 +/- 58) mg/L) and TF ((2.6 +/- 0.5) vs (2.5 +/- 0.6) g/L, (3.3 +/- 0.8) vs (2.9 +/- 0.6) g/L)were significantly higher in Group A than those in Group B (P < 0.05). CONCLUSION: With regards to lipid metabolism, protein synthesis and hepatocyte protection, structured triglycerides in parenteral nutrition is advantageous to standard MCT/LCT emulsion in severe hemorrhagic shock patients after resuscitation. PMID- 22781457 TI - [Relationship between antithrombin-III value with acute coronary syndrome and preprocedural TIMI flow grade]. AB - OBJECTIVE: To explore the differences of antiprothrombin-III (AT-III) value in patients with acute coronary syndrome (ACS) and stable angina pectoris (SAP) and examine the association of AT-III value with preprocedural thrombolysis in myocardial infarction (TIMI) flow in ACS patients. METHODS: This study prospectively included 121 hospitalized ACS patients between February 2011 to June 2011, including ST-segment elevation myocardial infarction (STEMI, n = 50), non-ST segment elevation myocardial infarction (NSTEMI, n = 32) and unstable angina (UAP, n = 39). Meanwhile, 50 SAP cases during the same period were selected as the control group. The AT-III levels were measured by chromogenic substrate method before coronary angiography for all patients. RESULTS: (1) The AT-III levels were significantly lower in the ACS patients than those in the SAP cases. (2) In the STEMI subgroup, the AT-III levels were markedly lower in the patients with preprocedural TIMI flow grade <= 2 versus those with preprocedural TIMI flow grade 3 (86% +/- 11% vs 93% +/- 9%, P < 0.05). (3) In the USTEMI/UAP subgroup, the mean levels of AT-III were obviously lower in the patients with preprocedural TIMI flow grade <= 2 than those with preprocedural TIMI flow grade 3 (85% +/- 8% vs 95% +/- 8%, P < 0.01) and were notably lower in the patients with the culprit lesion stenosis >= 70% versus those with stenosis < 70% (88% +/- 9% vs 94% +/- 9%, P < 0.01). (4) Multivariable analysis identified AT-III value as an independent predictor of impaired preprocedural TIMI flow grade of culprit coronary artery in ACS patients. CONCLUSION: The AT-III levels were significantly lower in the ACS patients than those in the SAP patients. The activity of AT-III is positively correlated with the TIMI flow grade in ACS patients. In contrast, the activity of AT-III is negatively correlated with the severity of culprit vessel stenosis in the patients with NSTEMI. Thus AT-III level may be used to distinguish high-risk populations in ACS patients at an early stage. PMID- 22781458 TI - [Features of proteinuria in Chinese male patients with Alport syndrome]. AB - OBJECTIVE: To explore the timing and course of proteinuria in Chinese patients with Alport syndrome (AS). METHODS: This retrospectively study included 118 unrelated male AS patients at Department of Pediatrics, Peking University First Hospital between 1994 and 2009. The clinical data of the onset age of proteinuria, the degree of proteinuria and the prevalence of microalbuminuria were analyzed. Urinary total protein was detected by the pyrogallol red protein dye-binding assay, urinary microalbumin by immunoturbidimetric assay and urinary creatinine level by alkaline kinetics. Microalbuminuria was detected when the microalbumin: creatinine ratio was > 30 mg/g on a single random midstream first morning urine sample. RESULTS: A total of 106 patients had proteinuria. The occurring or detecting age of proteinuria varied from 1 month to 27 years. Five patients (4.7%) were under 1 year of age and 15 patients (14.2%) at toddler's age. Among 43 cases with nephrotic-level proteinuria, 21 cases (48.8%) presented with nephrotic-level proteinuria at age 6 - 12 year. Both urine total protein and morning urine microalbumin measurements within 7 days were made in 53 patients. Microalbuminuria occurred in 4 of 5 patients with normal daily urinary protein excretion. All 48 patients had daily proteinuria > 0.15 g. Increased urinary microalbumin was detected in 4 of 5 patients with normal daily urinary protein excretion and 46 patients with daily proteinuria > 0.15 g. The consistency of urine microalbumin concentration and urine microalbumin-to-creatinine ratio was excellent in 51 patients. However, in 2 patients with slightly increased daily urine total protein, urine microalbumin concentration was normal while the urine microalbumin-to-creatinine ratio abnormal (> 30 mg/g). CONCLUSIONS: In AS males, proteinuria occurs earlier and progresses rapidly. Since microalbuminuria precedes the onset of proteinuria, either urine microalbumin concentration or urine microalbumin-to-creatinine ratio in morning specimens should be used for detecting microalbuminuria. And microalbuminuria may serve as an early endpoint in intervention trials. PMID- 22781459 TI - [Clinical analysis of multiple myeloma with extramedullary plasmacytomas]. AB - OBJECTIVE: To explore the clinical features, treatment and prognosis of multiple myeloma (MM) with extramedullary plasmacytomas (EM). METHODS: A total of 43 patients were enrolled and divided into 2 groups. Group-1 had 12 patients of EM occurring after the diagnosis of MM while Group-2 included 31 EM patients at the initial diagnosis of MM. RESULTS: The male-to-female proportion was 23:20 and there was a median age of 53 years. The distribution of different isotypes was IgG (n = 15), IgA (n = 9), IgD (n = 2), kappa light chain (n = 6), lambda light chain (n = 6), biclonal myeloma (n = 3) and nonsecretory myeloma (n = 2). The sites of complicating plasmacytoma included skin, muscle and spinal canal. Nine patients received bortezomib plus DECP (cisplatin, etoposide, cyclophosphamide and prednisone) and 2 patients underwent traditional chemotherapy in Group-1. The outcomes were as follows: complete remission (CR, n = 2), partial remission (PR, n = 4) and death (n = 5). And 11 patients received traditional chemotherapy in Group-2, 7 attained PR and 4 died. Twenty patients received bortezomib plus other chemotherapeutic drugs in Group-2. The outcomes were as follows: CR (n = 12), PR (n = 7) and death (n = 1). The median overall survival (OS) was 36 months (range: 10 - 120) in Group-1 and 23 months (range: 5 - 52) in Group-2 respectively. In Group-1, the estimated 3- and 5-year OS were 54.21% and 27.10% respectively. And in Group-2, the estimated 3- and 4-year OS were 39.83% and 13.28% respectively. CONCLUSIONS: The EM patients show aggressive, complicated and diverse clinical courses and the unusual manifestation of multiple organ involvement by plasma cells. Traditional chemotherapy has a poor efficacy and the prognosis is unfavorable, especially for EM with concurrent MM. The combined treatment of bortezomib with second-line chemotherapy may achieve curative effects. PMID- 22781460 TI - [Comparison of bowel function pre and post-sigmoid augmentation cystoplasty in spinal cord injury patients]. AB - OBJECTIVE: To explore the changes of bowel function in spinal cord injury (SCI) patients undergoing sigmoid augmentation cystoplasty. METHODS: From September 2005 to January 2011, 30 SCI patients undergoing sigmoid augmentation cystoplasty were surveyed by follow-up questionnaires at Beijing Charity hospital and Affiliated Hospital of Nantong University. RESULTS: Among them, 18 cases (60.0%) believed their defecation became softer and 18 cases (60.0%) thought their defecation time became shorter. The postoperative profiles of patient defecation traits and defecation time were better (P < 0.05), especially traumatic SCI patients (P < 0.05). CONCLUSION: The subtotal resection of sigmoid colon improves the defecation of spinal cord injury patients. The SCI patients undergoing sigmoid augmentation cystoplasty may avoid urinary tract dysfunctions and improve bowel dysfunction. PMID- 22781461 TI - [Esthetic evaluation of Cerec 3D anterior crowns]. AB - OBJECTIVE: To observe the short-term effect of clinical application of Cerec 3D anterior crowns. METHODS: A total of 16 patients were restored with 31 Cerec 3D anterior crowns. All restorations were stained before cementation. The evaluation started 1 week after luting. The restorations were examined in accordance with the modified US Public Health Service (USPHS) criteria at baseline and every 6 - 12 months. RESULTS: The observation period of 31 Cerec 3D anterior crowns varied from 8 to 33 months. The mean observation period was 22 months. All restorations scored A or B by modified USPHS standard. And 22 out of 31 restorations scored A for all criteria while 8 restorations scored B in color matching. Slight differences of translucency and chroma could be observed. Between baseline and follow-up examinations, insignificant shift from A-to B-rating occurred. CONCLUSION: Cerec 3D anterior crowns may achieve favorable short-term esthetic effects. PMID- 22781462 TI - [Experimental study of CTLA4Ig gene-modified dendritic cells transfused neonatally inducing asthmatic immune tolerance in adult mice]. AB - OBJECTIVE: To explore the effects of CTLA4Ig gene-modified dendritic cells on the mechanism of immune regulation in asthma with Th2 superiority. METHODS: Newborn BALB/c mice are randomly divided into 2 groups of AdCTLA4Ig-DC intervention and AdGFP modified dendritic cells (AdGFP-DC) intervention by randomization (n = 10 each). CTLA4Ig gene-modified dendritic cells (AdCTLA4Ig-DC) and AdGFP-DC were infused separately. Newborn BALB/c mice in both groups were fed for 6 - 8 weeks. Additional 6 - 8 weeks BALB/c mice were randomly divided into 2 groups of control and asthma (n = 10 each). The saline-sensitized/challenged mice received an intraperitoneal injection while inhalation was administered in the control group. Ovalbumin (OVA) was used similarly in the remaining three groups. The manifestations of OVA challenged mice in each group, bronchoalveolar lavage fluid (BALF) eosinophils and pathological changes in airway were observed to examine the effects of CTLA4Ig gene-modified dendritic cells on airway inflammation. The levels of IgE, Interleukin (IL)-4, IL-10 and IFN-gamma were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Rapid respiration and pulmonary inflammatory infiltration were obvious in the asthma group. CTLA4Ig gene-modified dendritic cells transfused neonatally significantly improved the symptoms of asthma in adulthood and reduced the infiltration of inflammatory cells in bronchial submucosa. The levels of IgE and IL-4 in serum and BALF in the AdCTLA4Ig-DC intervention group were significantly lower than those in the asthma group (IgE: (3.9 +/- 1.3)* 10(5) pg/ml vs (5.3 +/- 1.7)* 10(5) pg/ml and (22.9 +/ 11.8)* 10(3) pg/ml vs (122.0 +/- 59.6)* 10(3) pg/ml, IL-4: (70.5 +/- 7.0) pg/ml vs (88.7 +/- 9.2) pg/ml and (46.9 +/- 2.9) pg/ml vs (73.3 +/- 8.7) pg/ml, all P < 0.05). The levels of IL-10 in serum and BALF in the AdCTLA4Ig-DC intervention group were significantly higher than those in the asthma group ((442 +/- 8) pg/ml vs (227 +/- 11) pg/ml, (83 +/- 42) pg/ml vs (27 +/- 11) pg/ml, both P < 0.05). The levels of IFN-gamma in serum and BALF in AdCTLA4Ig-DC intervention group showed no significant difference with those in the asthma group (both P > 0.05). The eosinophil level in BALF was significantly lower than that in the asthma group ((18.5 +/- 1.9)* 10(4)/ml vs (62.3 +/- 6.7)* 10(4)/ml, P < 0.05). CONCLUSIONS: CTLA4Ig gene-modified dendritic cells transfused neonatally may reduce the secretion of Th2 cytokines in OVA-sensitized/challenged adult mice. The expression of CTLA4Ig gene induces immune tolerance in asthma. PMID- 22781463 TI - [Expressions of endoplasmic reticulum stress associated proteins in livers of severely burned rats]. AB - OBJECTIVE: To explore the expression of endoplasmic reticulum stress (ERS) associated proteins in livers of severely burned rats and examine its potential significance. METHODS: Sixty-four Wistar rats were randomly divided into the control and burn groups (30% total body surface area full-thickness thermal injury) (n = 32 each). Livers were harvested at Day 1, 4, 7, 14 post-burn. Western blot was used to detect the expressions of endoplasmic reticulum stress associated proteins glucose regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), active caspase-12 and active caspase-3. Hepatic apoptosis was assessed by the assay of terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL). RESULTS: Compared with the control group, the expression of GRP78 became elevated at Day 1, 4, 7, 14 post-burn (1.29 +/- 0.11 vs 1.00 +/- 0.00, 1.28 +/- 0.12 vs 0.95 +/- 0.16, 1.29 +/- 0.14 vs 0.93 +/- 0.06, 1.41 +/- 0.17 vs 1.02 +/- 0.13 respectively); the expression of CHOP was higher at Day 1, 4 (1.72 +/- 0.07 vs 1.00 +/- 0.00, 1.82 +/- 0.18 vs 1.46 +/- 0.08 respectively) while active caspase-12 and active caspase-3 increased at Day 1, 4, 7 post-burn (2.05 +/- 0.65 vs 1.00 +/- 0.00, 2.16 +/- 0.69 vs 0.95 +/- 0.21, 1.98 +/- 0.56 vs 0.90 +/- 0.22; 1.96 +/- 0.15 vs 1.00 +/- 0.00, 1.40 +/- 0.14 vs 1.07 +/- 0.12, 1.77 +/- 0.17 vs 1.15 +/- 0.21 respectively); the apoptotic index(%) of hepatocytes was higher at Day 1, 4, 7, 14 post-burn (27.20 +/- 3.63 vs 5.00 +/- 0.71, 16.40 +/- 1.52 vs 5.40 +/- 1.14, 27.60 +/- 1.82 vs 7.40 +/- 1.14, 10.20 +/- 1.92 vs 5.20 +/- 1.64 respectively). All results were statistically significant (all P < 0.05). CONCLUSION: ERS activates and expressions of associated proteins GRP78, CHOP, active caspase-12 and active caspase-3 increase in livers of severely burned rats. PMID- 22781464 TI - Genome-wide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation. AB - BACKGROUND: Neonatal cerebellar cortical degeneration is a neurodegenerative disease described in several canine breeds including the Beagle. Affected Beagles are unable to ambulate normally from the onset of walking and the main pathological findings include Purkinje cell loss with swollen dendritic processes. Previous reports suggest an autosomal recessive mode of inheritance. The development of massively parallel sequencing techniques has presented the opportunity to investigate individual clinical cases using genome-wide sequencing approaches. We used genome-wide mRNA sequencing (mRNA-seq) of cerebellum tissue from a single Beagle with neonatal cerebellar cortical degeneration as a method of candidate gene sequencing, with the aim of identifying the causal mutation. RESULTS: A four-week old Beagle dog presented with progressive signs of cerebellar ataxia and the owner elected euthanasia. Histopathology revealed findings consistent with cerebellar cortical degeneration. Genome-wide mRNA sequencing (mRNA-seq) of RNA from cerebellum tissue was used as a method of candidate gene sequencing. After analysis of the canine orthologues of human spinocerebellar ataxia associated genes, we identified a homozygous 8 bp deletion in the beta-III spectrin gene, SPTBN2, associated with spinocerebellar type 5 in humans. Genotype analysis of the sire, dam, ten clinically unaffected siblings, and an affected sibling from a previous litter, showed the mutation to fully segregate with the disorder. Previous studies have shown that beta-III spectrin is critical for Purkinje cell development, and the absence of this protein can lead to cell damage through excitotoxicity, consistent with the observed Purkinje cell loss, degeneration of dendritic processes and associated neurological dysfunction in this Beagle. CONCLUSIONS: An 8 bp deletion in the SPTBN2 gene encoding beta-III spectrin is associated with neonatal cerebellar cortical degeneration in Beagle dogs. This study shows that mRNA-seq is a feasible method of screening candidate genes for mutations associated with rare diseases when a suitable tissue resource is available. PMID- 22781465 TI - Is it really important to form a big bubble in DALK to enhance the visual acuity? AB - OBJECTIVES: The aim of this study was to investigate the prognosis of visual acuity (VA) in the patients with keratoconus, who underwent deep anterior lamellar keratoplasty (DALK) with a successful big bubble or lamellar dissection. METHODS: Sixty-eight eyes of 60 patients with keratoconus, who underwent DALK using the big-bubble technique, were enrolled in this retrospective comparative study. The VA and refractive errors were assessed before the operation and, thereafter, at months 1, 3, 6, and 12 after the operation (1) in the patients who achieved a big-bubble formation, and in those who required layer-by-layer lamellar dissection (2) to reach the Descemet membrane. RESULTS: Successful big bubble was achieved in 50 eyes (73.5 %) (group 1), and lamellar dissection was performed in 18 eyes (26.5 %) (group 2). The mean follow-up period was 22.4+/-6.2 months in group 1 and 23.7+/-7.8 months in group 2 (P=0.562). Although best corrected visual acuity (BCVA) values observed at months 1 and 3 were significantly higher in group 1 than in group 2 (P=0.016 and P=0.024, respectively), there was no statistically significant difference between the two groups for BCVA values observed at months 6 and 12 (P=0.412 and P=0.528, respectively). CONCLUSIONS: Although the visual recovery was delayed in the early postoperative follow-up because of residual stroma in lamellar dissection, the final results were comparable between the achievement of big-bubble formation and lamellar dissection. PMID- 22781466 TI - Management of bullous keratopathy-related ulcer with autologous serum. AB - PURPOSE: The aim of this study was to report the use of autologous serum eyedrops (ASEs) for resolution of a corneal ulcer secondary to bullous keratopathy. METHODS: This is a case report. RESULTS: A 66-year-old patient presented with an infected ulcer and hypopyon while using a bandage contact lens for bullous keratopathy. Staphylococcus warneri infection was treated with systemic and topical antibiotics, and ASEs were subsequently administered to enhance reepithelialization and to avoid the need for a bandage contact lens. The ASE treatment led to closure of the epithelium layer within 3 weeks, and it was subsequently tapered over the next 3 months. The clinical picture remained stable subjectively and objectively during the 7 months of follow-up. DISCUSSION: To the best of our knowledge, this is the first report of successful use of ASEs in treating and preventing recurrence of ulcers in the context of bullous keratopathy. PMID- 22781467 TI - Very long-term clinical follow-up after fractional flow reserve-guided coronary revascularization. AB - BACKGROUND: Randomized trials using measurement of fractional flow reserve (FFR) to guide percutaneous coronary intervention (PCI) have demonstrated both safety and efficacy with regard to cardiac events. Real-world, long-term outcomes using an FFR-based revascularization strategy are unknown. METHODS: Prospective clinical data were collected on consecutive patients referred for coronary angiography and found to have lesions of intermediate severity where the operators were unable to make a decision regarding revascularization based on angiographic, clinical, and stress testing parameters. FFR was measured on intermediate lesions, and revascularization was deferred on those lesions with a measurement >0.8. Clinical outcomes of interest included death, myocardial infarction, and late revascularization status. RESULTS: A total of 151 patients were included in this study. Fifty-seven patients (37.7%) underwent revascularization based on their FFR measurement. The mean length of follow-up was 6.1 years (range, 5-10 years). Follow-up was completed in 97.0%. At the end of the follow-up period, 107 patients (70.9%) were alive. Late revascularization had been performed in 18 patients (11.9%). Comparing the initial revascularization group with the group in which revascularization was deferred, 64.9% and 74.5% were alive, respectively (P=.29). Of the initial revascularization group, 12.3% had undergone late revascularization of the lesion on which FFR was originally performed, compared with 11.7% in the deferred group (P=.99). CONCLUSIONS: FFR is a useful adjunct to coronary angiography in selecting patients with lesions of intermediate angiographic severity in whom coronary revascularization may be safely deferred. PMID- 22781468 TI - Multicenter international registry of unprotected left main coronary artery percutaneous coronary intervention with everolimus-eluting stents. AB - OBJECTIVE: The aim of this study was to assess the clinical outcomes of percutaneous coronary intervention (PCI) with everolimus-eluting stents (EES) for the treatment of unprotected left main coronary artery (ULMCA) disease. BACKGROUND: The standard of care for the treatment of ULMCA disease is coronary artery bypass grafting (CABG). Data suggest that PCI with drug-eluting stents is a viable alternative to CABG for the treatment of ULMCA disease. Randomized trials demonstrated superior event-free survival with EES compared with paclitaxel-eluting stents in non-ULMCA lesions. However, data with ULMCA PCI with EES are limited. METHODS: This multicenter international registry included 178 patients from the United States, South Korea, and Italy who underwent ULMCA PCI with EES from 2008 to 2010. The primary endpoint was freedom from target lesion failure (TLF), defined as cardiac death, myocardial infarction (MI), and ischemia driven target lesion revascularization (TLR) at 1 year. RESULTS: At 30 days, 4 patients (2.2%) died from cardiac causes, and no patient experienced MI or TLR. One-year freedom from TLF was 94.4%. One-year freedom from cardiac death, MI, and ischemia-driven TLR was 96.6%, 98.9%, and 98.3%, respectively. Two patients (1.1%) had definite or probable stent thrombosis. CONCLUSION: PCI with EES is safe and effective and may be a viable option for the treatment of ULMCA disease. PMID- 22781469 TI - Vasomotor response to different endothelium-dependent vasodilators in an animal model. AB - BACKGROUND AND OBJECTIVES: Incomplete re-endothelialization of stents can be revealed as paradoxical vasoconstriction with endothelium-dependent vasodilators. As no consensus exists about the best method or agent, our objective is to analyze the response to different drugs in a coronary swine model. METHODS: Twenty-seven stents were implanted in 9 domestic swine. The vessel diameter of proximal and distal segments (>=5 mm) was assessed immediately post implantation. Different endothelium-dependent vasodilators were used: intracoronary (IC) acetylcholine, 20 MUg (A2) and 40 MUg (A4), IC serotonin (S), 100 MUg, and isoproterenol (I), intravenous infusion. The results are presented as constriction (%) compared with maximal vasodilation with IC nitroglycerin (N, 200 MUg). RESULTS: In 10 vessels (37%), A4 provoked an occlusive spasm. Acetylcholine induced a higher degree of vasoconstriction (A4, 42 +/- 39%; A2, 16 +/- 14%) than the rest of the agonists (S, 6 +/- 12%; I, 6 +/- 11%; P<.01). The constriction rate was not related to the induced hemodynamic changes. CONCLUSIONS: After focal endothelial denudation in a coronary swine model, the constriction rate induced by different endothelium-dependent vasodilators is highly variable. The highest value is observed after IC acetylcholine bolus. The constriction rate does not correlate with the observed hemodynamic changes. PMID- 22781470 TI - Impact of preprocedural TIMI flow on myocardial perfusion, distal embolization and mortality in patients with ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb/IIIa inhibitors. AB - BACKGROUND: Despite optimal epicardial recanalization, primary angioplasty for ST elevation myocardial infarction (STEMI) is still associated with suboptimal reperfusion in a relatively large proportion of patients. The aim of the current study was to evaluate the impact of preprocedural TIMI flow on myocardial perfusion, distal embolization, and survival among STEMI patients undergoing primary angioplasty with glycoprotein (GP) IIb/IIIa inhibitors. METHODS: Our population is represented by a total of 1637 patients undergoing primary angioplasty for STEMI treated with GP IIb/IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. RESULTS: Poor preprocedural TIMI flow (TIMI 0-1) was observed in 1039 patients (63.5%), and was associated with higher Killip class at presentation (P=.006), longer time to-treatment (P=.03), less often with early administration of GP IIb/IIIa inhibitors (P<.001), impaired postprocedural epicardial (P=.001) and myocardial perfusion (determined by myocardial blush grade, P<.001 and/or ST-segment resolution (P<.001), and distal embolization (P=.041). At 206 +/- 158 days follow up, poor preprocedural recanalization was associated with a significantly higher mortality (adjusted odds ratio, 0.58; 95% CI, 0.34-0.96; P=.034). CONCLUSION: This study shows that among patients with STEMI undergoing primary angioplasty with GP IIb/IIIa inhibitors, poor preprocedural TIMI flow is associated with higher incidence of distal embolization and impaired epicardial and myocardial perfusion, and significantly higher mortality. PMID- 22781471 TI - Bleeding and vascular complications at the femoral access site following percutaneous coronary intervention (PCI): an evaluation of hemostasis strategies. AB - BACKGROUND: Previous research found at least one vascular closure device (VCD) to be associated with excess vascular complications, compared to manual compression (MC) controls, following cardiac catheterization. Since that time, several more VCDs have been approved by the Food and Drug Administration (FDA). This research evaluates the safety profiles of current frequently used VCDs and other hemostasis strategies. METHODS: Of 1089 sites that submitted data to the CathPCI Registry from 2005 through the second quarter of 2009, a total of 1,819,611 percutaneous coronary intervention (PCI) procedures performed via femoral access site were analyzed. Assessed outcomes included bleeding, femoral artery occlusion, embolization, artery dissection, pseudoaneurysm, and arteriovenous fistula. Seven types of hemostasis strategy were evaluated for rate of "any bleeding or vascular complication" compared to MC controls, using hierarchical multiple logistic regression analysis, controlling for demographic factors, type of hemostasis, several indices of co-morbidity, and other potential confounding variables. Rates for different types of hemostasis strategy were plotted over time, using linear regression analysis. RESULTS: Four of the VCDs and hemostasis patches demonstrated significantly lower bleeding or vascular complication rates than MC controls: Angio-Seal (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.65-0.70); Perclose (OR, 0.54; CI, 0.51-0.57); StarClose (OR, 0.77; CI, 0.72-0.82); Boomerang Closure Wire (OR, 0.63; CI, 0.53-0.75); and hemostasis patches (OR, 0.70; CI, 0.67-0.74). All types of hemostasis strategy, including MC, exhibited reduced complication rates over time. All trends were statistically significant except one. CONCLUSIONS: This large, nationally representative observational study demonstrated better safety profiles for most of the frequently used VCDs, compared to MC controls. PMID- 22781472 TI - Safety and efficacy of drug-eluting balloons in the treatment of drug-eluting in stent restenosis: experience of a tertiary care hospital. AB - BACKGROUND: The advent of drug-eluting balloons (DEBs) is a promising development for coronary revascularization procedures, especially for in-stent restenosis (ISR). This study aims to highlight our experience with DEBs in the treatment of drug-eluting ISR at a tertiary care hospital in Pakistan. METHODS: All patients presenting to our institution from August 2008 to February 2011 with significant drug-eluting in-stent restenosis (DES-ISR) who were eligible to receive treatment via DEB were included in the analysis. Patient baseline characteristics and angiographic data about the lesion characteristics were obtained. Postprocedural and follow-up endpoints, including cardiac death, myocardial infarction, and repeat revascularization, ie, major adverse cardiovascular events (MACE), were included in the analysis. RESULTS: A total of 26 patients received treatment with DEB in the study period, with a significant number having major predisposing factors for the development of ischemic heart disease (IHD; 46% diabetics; 92% hypertensives). The culprit lesion was most commonly identified in the left anterior descending (31%), with presence of American College of Cardiology/American Heart Association lesion type C in 68% of patients. The SeQuent Please paclitaxel-eluting balloon (B. Braun) was used for revascularization. Patients were followed for a median of 16 months. Only 5 patients (19%) developed MACE during this period. CONCLUSION: Our experience demonstrates the effectiveness of DEBs in the treatment of drug-eluting ISR, especially in complex lesions with patients having significant risk factors for development of IHD. However, further studies are needed to define their indications in this role. PMID- 22781473 TI - Ultrasonic evaluation of the radial artery diameter in a local population from Texas. AB - BACKGROUND: Radial access is the preferred route for cardiac catheterization; however, small radial arterial diameters can make complex procedures difficult. The assessment of radial artery diameters prior to intervention may be beneficial for the interventional cardiologist. Our aim was to measure the diameter of radial arteries in a study sample from our population, and to analyze the feasibility of using larger sheaths for radial interventions. METHODS: The right radial artery diameter of 100 volunteers was measured using an ultrasound technique. A logistic regression analysis was performed to identify factors associated with small arterial diameters. RESULTS: The average age of our sample was 35 years, 40% were male, and the mean body mass index (BMI) was 27 kg/m2. The mean right arterial diameter for our population was 2.22 +/- 0.35 mm. No strong direct association was found between diameters with age, height, weight, and body surface area. Forty-two percent of the patients had diameters larger than 5 Fr sheaths, 20% of the subjects had a diameter larger than 6 Fr sheaths, and 5% of the patients had diameters larger than 7 Fr sheaths. Logistic regression analysis revealed that female volunteers were associated with smaller arterial diameters (odds ratio [OR], 4.0; confidence interval [CI], 1.51-10.51; P=.005), while increases in BMI were associated with larger arterial diameters (OR, 0.21; CI, 0.07-0.61; P=.004). CONCLUSION: Six Fr sheaths can be used in a significant proportion of our population. Careful selection of male patients with a larger BMI may help the interventionist in advance for planning a radial procedure with larger sheaths. PMID- 22781474 TI - Transcatheter aortic valve implantation with either CoreValve or SAPIEN XT devices in patients with a single coronary artery. AB - Transcatheter aortic valve implantation (TAVI) is associated with a risk of coronary obstruction. This complication is potentially lethal when the origin of the coronary arteries is anomalous. We describe two cases of TAVI with the SAPIEN XT (Edwards Lifesciences) and CoreValve devices (Medtronic) in patients with a single coronary artery. The tools and techniques used to anticipate the risk of acute coronary occlusion are discussed. PMID- 22781475 TI - Transcatheter aortic valve implantation in patients with single coronary artery. PMID- 22781476 TI - Safety and efficacy of transradial access in coronary angiography: 8-year experience. AB - AIMS: The transradial approach (TRA) in coronary angiography is used less frequently than the transfemoral approach; the learning curve and transradial failure (TRF) have slowed its widespread use. We evaluate the incidence, causes, and predictors of TRF in TRA coronary angiographies in an unselected population. METHODS AND RESULTS: All elective coronary angiographies using TRA from January 2002 to December 2009 were analyzed in this single-center, prospective, observational study. TRF occurred in 465/8463 procedures (5.5%). The main causes of TRF were puncture failure in 48.3% and tortuous brachiocephalic arteries in 22.8% of cases. The annual TRF percentage decreased from 9.1% in 2002 to 4.1% in 2009 (P<.001). In a multivariable regression model, the independent factors associated with TRF included use of >3 catheters (odds ratio [OR], 3.973; confidence interval [CI], 3.198-4.937), abnormal Allen test (OR, 3.231; CI, 1.839 5.676), radial spasm (OR, 3.896; CI, 2.903-5.229), peripheral vascular disease (OR, 1.900; CI, 1.426-2.532), female sex (OR, 1.451; CI, 1.094-1.925), and age >80 years (OR, 1.441; CI, 1.020-2.036). Intra-arterial administration of verapamil (OR, 0.137; CI, 0.098-0.190) and nitroglycerin (OR, 0.455; CI, 0.317 0.653), and height (OR, 0.974; CI, 0.959-0.990) reduced the risk of TRF. CONCLUSIONS: Experience with TRA was associated with a low incidence of TRF. Independent factors associated with TRF were identified. PMID- 22781477 TI - Left radial artery access to a descending aortic saphenous vein graft to circumflex coronary artery for angioplasty. AB - As data continue to show the benefits of radial artery access, the versatility and feasibility of this approach for complex coronary interventions is continually tested. We report successful angioplasty of a circumflex obtuse marginal coronary lesion crossed retrogradely via a saphenous vein graft arising from the descending aorta, accessed via the left radial artery. PMID- 22781478 TI - Perfection of precise ostial stent placement. AB - Ostial lesions, including aorta-ostial lesions and Medina 001 bifurcation lesions, are known to create difficulty in precise stent placement. There are many techniques used to help in precise ostial stent placement; these include using multiple angiographic views to assist in placement, the use of the Ostial Pro device, the aorta flowing wire technique, Szabo (anchor-wire) techniques, the T-stent and small protrusion (TAP) technique, the cross-over 1-stent technique, and new dedicated ostial stents. In this review, we summarize these different techniques and show that there is no universal technique that allows for perfect ostial stent placement. PMID- 22781479 TI - Role of internal mammary artery bypass grafts in retrograde chronic total occlusion interventions. AB - The role of internal mammary artery grafts in facilitating retrograde chronic total occlusion interventions is controversial. We describe two cases demonstrating: (a) retrograde wiring via a left internal mammary artery graft; and (b) using the left internal mammary graft for vessel visualization while retrograde crossing to the right coronary artery was achieved via the native left main coronary artery (triple arterial access). The internal mammary artery grafts can facilitate retrograde chronic total occlusion interventions, but should be used with caution to minimize the risk of injury. PMID- 22781480 TI - Hemodynamic findings of spontaneously recanalized coronary thrombus. AB - This case presented is a patient with non-ST elevation myocardial infarction with angiographic non-flow limiting linear opacity in coronary artery with fractional flow reserve in ischemic range secondary to recanalized organized thrombus. PMID- 22781481 TI - Challenges associated with use of the GuideLiner catheter in percutaneous coronary interventions. AB - The GuideLiner catheter is an easy-to-use guide catheter extension that can facilitate vessel engagement and equipment delivery. We present two cases that illustrate two potential challenges associated with use of the GuideLiner catheter: (1) stent loss and deformation during attempts to advance it through the GuideLiner catheter collar; and (2) displacement of the GuideLiner catheter distal marker into a coronary artery. Awareness of these potential complications may render safer the use of this valuable interventional tool. PMID- 22781482 TI - Inapparent atrial flutter due to atrial dissociation. AB - Percutaneous and surgical procedures intended to potentially cure atrial fibrillation require creating lines of conduction block in specific locations throughout the atrial chambers. In patients presenting with recurrent atrial fibrillation, repeat procedures are often performed, resulting in more extensive regions of conduction block and the potential for regions of dissociated atrial rhythms. The present case describes a patient post-multiple ablation procedures who presented with a symptomatic atrial arrhythmia, the mechanism of which was hidden by the presence of extensive atrial dissociation. Electrophysiologic study revealed the appropriate mechanism and a beneficial ablative procedure was then successfully accomplished. PMID- 22781483 TI - Voluminous fistula between the right coronary artery and a branch of the pulmonary artery causing myocardial ischemia. AB - A 76-year-old female patient was referred to our institution because of typical chest pain. A continuous murmur was audible at the lower sternal border. A transthoracic echocardiogram showed non-dilated right and left ventricles with mild left ventricular inferior wall hypokinesia and an exercise stress test was positive for myocardial ischemia. A coronary angiogram showed no signs of atherosclerotic coronary artery disease, but it revealed a voluminous fistula between the proximal segment of the right coronary artery and a branch of the pulmonary artery, which was percutaneously closed using 3 embolization coils. Such late presentation of a voluminous coronary fistula is extremely rare and, to the best of our knowledge, very few case reports like this have been published. PMID- 22781484 TI - Coronary artery disease: not always the case for ST-elevation myocardial infarction. AB - We report a case of an acute ST-T elevation myocardial infarction in a middle aged female with a mechanical mitral valve prosthesis and subtherapeutic INR levels. We performed a primary coronary intervention, using a thromboaspiration catheter. After blood clot aspiration, a TIMI III flow was restored and no residual lesions remained at the site of the occlusion. A transesophageal echo revealed a movable thrombus over the mechanical mitral valve prosthesis and patient underwent subsequent mitral valve replacement. Embolic myocardial infarction remains underdiagnosed. A high level of suspicion and the quest of the source of embolus are crucial. PMID- 22781485 TI - Right pulmonary artery to left atrium fistula: transcatheter closure without conventional venovenous loop. AB - Right pulmonary artery to left atrium fistula is a rare anatomic variation of pulmonary arteriovenous malformation in which the initial connection exists between a pulmonary artery and a pulmonary vein, but during vascular development the pulmonary vein gets incorporated into the left atrium. Though nearly 60 such cases have been reported in literature, only 6 cases have been tackled by transcatheter technique with various types of devices and coils. This is a case where we demonstrate that large fistulae can be closed successfully with an atrial septal occluder without a conventional method of transseptal puncture and venovenous loop formation. PMID- 22781486 TI - The use of a wire control catheter to treat complex pulmonary artery or vein anatomy. AB - The difficult performance of certain percutaneous interventions in the field of congenital heart disease is well known. Crossing pulmonary arteries in patients who have previously undergone surgical repair or stenotic pulmonary veins in infants can be typical examples of these technical challenges in the catheterization laboratory. The Venture wire 6 Fr control catheter (St Jude Medical) is compatible with a steerable tapered radiopaque tip that can be manually angulated (up to 90 degrees ) by clockwise rotation of a knob located in the proximal handle. This mechanism directs any 0.014" guidewire and provides back-up support. This catheter has been successfully used in coronary artery intervention for crossing severely tortuous vessels, extreme angulations of side branch ostia, jailed stents, saphenous vein graft anastomoses, and chronic total occlusions. We report the first use of the Venture wire control catheter (St Jude Medical) in the field of congenital heart disease. Patient #1 was diagnosed with pulmonary atresia and ventricular septal defect and had a proximally migrated stent in the pulmonary trunk and severe left pulmonary artery stenosis. We have used this catheter in order to cross this stent and perform left pulmonary artery stent placement. Patient #2 had postoperative vein restenosis after surgery. The Venture catheter was used to reach the obstructed insertion of the right medium lobe pulmonary vein from a transseptal approach. Techniques from coronary interventional colleagues can help interventional cardiologists in the field of congenital heart disease to treat complex situations. PMID- 22781487 TI - Substrate for complications. AB - Acute stent thrombosis is a rare, life-threatening, and challenging complication of left main stenting. Equally challenging is treating a chronic saphenous vein graft occlusion. Though considered class III indication per ACC/AHA guidelines, the saphenous vein graft may be the only potential conduit for revascularization. Coronary perforation during chronic total occlusion revascularization after coronary artery bypass grafting is not rare but the post-coronary artery bypass grafting state itself may provide some protection against tamponade by virtue of the adhesions between pericardium and epicardium consequent to surgery. We present a case of multiple complications in one patient and a good outcome after treating each of the above complications. PMID- 22781488 TI - Percutaneous coronary intervention via transulnar sheathless approach. AB - Diagnostic and interventional coronary procedures via cannulation of the radial artery have proven to be useful in patients with acute coronary syndrome (ACS) ST segment elevation myocardial infarction, non-ST-segment elevation ACS, and non ACS clinical syndromes. In many patients, vascular access and catheter advancement can be difficult due to vessel size, vasospasm, anatomical branching variations, and catheter manipulation. The ulnar artery may prove to be a preferred alternative in many cases where the radial artery is unable to be utilized. Furthermore, the use of large caliber catheters through these smaller caliber vessels also limits the use of some devices for treatment of bifurcation lesions. We report the use of a sheathless percutaneous coronary intervention through the ulnar artery. In this case a sheathless technique was shown. The sheathless catheter has already been shown as safe in small case series and in a multicenter registry. With a smaller luminal diameter than that of traditional sheath systems, the risk of vasospasm, vascular damage, radial artery occlusion, and bleeding complications, even in maximal platelet inhibition, is theoretically reduced. PMID- 22781489 TI - Global prevalence of anxiety disorders: a systematic review and meta-regression. AB - BACKGROUND: The literature describing the global prevalence of anxiety disorders is highly variable. A systematic review and meta-regression were undertaken to estimate the prevalence of anxiety disorders and to identify factors that may influence these estimates. The findings will inform the new Global Burden of Disease study. Method A systematic review identified prevalence studies of anxiety disorders published between 1980 and 2009. Electronic databases, reference lists, review articles and monographs were searched and experts then contacted to identify missing studies. Substantive and methodological factors associated with inter-study variability were identified through meta-regression analyses and the global prevalence of anxiety disorders was calculated adjusting for study methodology. RESULTS: The prevalence of anxiety disorders was obtained from 87 studies across 44 countries. Estimates of current prevalence ranged between 0.9% and 28.3% and past-year prevalence between 2.4% and 29.8%. Substantive factors including gender, age, culture, conflict and economic status, and urbanicity accounted for the greatest proportion of variability. Methodological factors in the final multivariate model (prevalence period, number of disorders and diagnostic instrument) explained an additional 13% of variance between studies. The global current prevalence of anxiety disorders adjusted for methodological differences was 7.3% (4.8-10.9%) and ranged from 5.3% (3.5-8.1%) in African cultures to 10.4% (7.0-15.5%) in Euro/Anglo cultures. CONCLUSIONS: Anxiety disorders are common and the substantive and methodological factors identified here explain much of the variability in prevalence estimates. Specific attention should be paid to cultural differences in responses to survey instruments for anxiety disorders. PMID- 22781490 TI - Evaluation of different culture media for the isolation and growth of the fastidious Vibrio tapetis, the causative agent of brown ring disease. AB - Thirteen culture media were evaluated at two temperatures for the growth and isolation of Vibrio tapetis. The bacterium showed similar growth dynamics at 15 degrees C or 25 degrees C, being faster at 15 degrees C regardless the general media employed. Best growth of V. tapetis was obtained on Agar Seawater (ASWT) (1.7 * 10(6)cfu/ml), Mannitol Marine Agar (MMA) (2.6 * 10(6)cfu/ml), and Mannitol Trypticase Soy Agar (MTSA-1) (1.9 * 10(6)cfu/ml), being slightly lower on Marine Agar (MA) (5.0 * 10(5)cfu/ml). Growth was poor on TCBS and nule in the other media containing bile salts, indicating their inhibitory effect on the V. tapetis growth. Recovery of V. tapetis from mixed Vibrio populations, differing in acid production from sucrose and mannitol, was only possible using the selective medium MMA at both temperatures. The use of ASWT or MA at 15 degrees C for the routinary growth of V. tapetis, and MMA for isolation of V. tapetis from bivalve samples is recommended. PMID- 22781491 TI - Ten types of breast cancer? PMID- 22781492 TI - Maximum rate of pressure development and maximal relaxation rate of respiratory muscles in patients with cystic fibrosis. AB - BACKGROUND: Respiratory muscle function in patients with cystic fibrosis (CF) has been studied by measurement of maximal inspiratory pressure (P(Imax)), maximal expiratory pressure (P(Emax)), and the pressure-time index of the respiratory muscles (PTI(mus)). The maximum rate of pressure development (MRPD) during P(Imax) (MRPD-P(Imax)), MRPD during P(Emax) (MRPD-P(Emax)), maximal relaxation rate (MRR) during P(Imax) (MRR-P(imax)), and MRR during P(Emax) (MRR-P(Emax)) have not been studied in CF. Our aim was to study MRPD and MRR and investigate their possible application as accessory indices of respiratory muscle function in patients with CF. METHODS: FEVY, FVC, and maximal expiratory flow between 25% and 75% of vital capacity, body mass index (BMI), upper arm muscle area, P(imax), P(Emax), PTI(mus), MRPD-P(Imax), MRPD-P(Emax), MRR-P(imax), and MRR-P(Emax) were assessed in 123 CF patients and in a control group of 123 healthy subjects matched for age and sex. RESULTS: MRR-P(Emax) was significantly increased and MRPD-P(Emax) was significantly decreased in the CF patients, compared to the healthy controls. In the CF patients MRR-P(Imax) was significantly related to PTI(mus) (P = .02), FEV1 (P = .03), FVC (P = .001), BMI (P < .001), and upper arm muscle area (P < .001). In the CF patients, MRPD-P(Imax) and MRPD- P(Emax) were significantly related to upper arm muscle area (P < .001), BMI (P < .001 and P = .01, respectively), P(Imax) (P < .001), and P(Emax) (P < .001). CONCLUSIONS: The CF patients exhibited increased MRR and decreased MRPD during maximal respiratory effort, compared to controls. The differences in MRR-P(imax) and MRPD-P(Imax) between the controls and the complete group of CF patients were not significant. MRPD and MRR were significantly related to nutritional and pulmonary function impairment in CF patients. MRPD strongly correlated to maximal respiratory muscle pressures, and MRR strongly correlated to PTI(mus) in patients with CF. These findings suggest that CF patients are at increased risk of respiratory muscle fatigue. Regular determination of MRPD and MRR may be clinically useful in CF patients and help to initiate inspiratory muscle training and noninvasive ventilation. PMID- 22781493 TI - Ruptured hemiarch and descending thoracic aorta aneurysm: hybrid treatment. AB - Ruptured aortic arch aneurysm is a life threatening disease. Surgical repair has an high perioperative mortality rate and totally endovascular treatment is a challenge. Hybrid repair has been proposed as a valuable approach. We report the case of a patient with a contained rupture of aortic arch aneurysm. We treated him with a debranching of supraortic vessels with carotid-carotid and carotid subclavian bypass and deployment of two enodgrafts in two different times. We consider hybrid treatment for arch and hemiarch a feasible option for aortic arch aneurysms in non emergent and in an emergency setting with an improvement in perioperative morbidity and mortality. PMID- 22781494 TI - Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact. AB - In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death. PMID- 22781496 TI - Infusion of Sydenham's chorea antibodies in striatum with up-regulated dopaminergic receptors: a pilot study to investigate the potential of SC antibodies to increase dopaminergic activity. AB - BACKGROUND: Sydenham's chorea (SC) is a neurological manifestation of rheumatic fever. Autoimmune mechanism of SC is supported by clinical improvement with immunomodulatory therapy; presence of circulating serum anti-basal ganglia antibodies; increase in Th2 group of cytokines in serum and CSF of patients. However, a role of the antibodies in the pathogenesis can only be established by their passive transfer. Chorea is a manifestation clearly related to increased dopaminergic (DA) activity. The purpose of this study was to investigate the potential of antibodies from patients with Sydenham's chorea to cause behavior alterations on rats with unilateral post-synaptic dopamine receptor up regulation. METHODS: Rats previously submitted to 6-hydroxidopamine (6-OH-DA) unilateral lesion of substantia nigra pars compacta (SNc) and tested with apomorphine to ensure DA receptors up regulation, received intrastriatal infusion of antibodies from SC patients (n=4) or healthy controls (n=3) during 48 h. 24h post infusion initiation (24PI) and 48 h post infusion initiation (48PI), we registered the occurrence of spontaneous contra lateral rotations (CLR). FINDINGS: SC group exhibited significantly higher number of CLR than control group at 24PI (p=0.049) and 48PI (p=0.048). CONCLUSION: The limited sample of the present study restricts us to affirm that SC is really an immune-mediated condition. However the significant result of this pilot study points to preliminary evidence that SC antibodies may affect DA activity in rats with up regulated striatal DA receptors. PMID- 22781495 TI - Oligodendrocyte progenitor cells derived from mouse embryonic stem cells give rise to type-1 and type-2 astrocytes in vitro. AB - Oligodendrocyte progenitor cells (OPCs) in primary culture can give rise to mature oligodendrocytes and type-2, but not type-1 astrocytes depending on the culture conditions. The OPCs thus are called oligodendrocyte-type-2 astrocyte (O2 A) progenitor cells. Mouse embryonic stem cells (mESCs) have been efficiently differentiated into OPCs; however, the fate plasticity of mESC-derived OPCs is not well characterized. In the present study, using GFP-Olig2 mESC line, we showed that the Olig2(+)/GFP(+)/A2B5(+)/NG2(+) OPCs derived from GFP-Olig2 mESCs can mature into oligodendrocytes when co-cultured with mESC-derived neurons. Interestingly, when induced to astrocytic differentiation by bone morphogenetic protein-4, these mESC-derived OPCs can not only generate type-2 astrocytes, but also type-1 astrocytes. These results challenge the dogma that OPCs in culture can only generate type-2, but not type-1 astrocytes, and support the in vivo finding that during perinatal development, OPCs can give rise to a subset of type 1 astrocytes. PMID- 22781497 TI - Adaptive reorganization of cortical networks in Alzheimer's disease. AB - OBJECTIVE: The impact of neuronal cell loss associated with Alzheimer's disease (AD) on the network organization of the brain is poorly understood. Here we investigated whether modifications in resting-state functional connectivity (FC) are associated with cognitive function of AD patients. METHODS: High-density electroencephalograms (EEGs) were obtained from patients with early stages of AD and elderly healthy controls. Cortical oscillations were reconstructed with an adaptive spatial filter. Maps of imaginary coherence (IC) between brain areas were compared between groups and correlated with cognitive performance. RESULTS: Parietal and medial temporal lobes of AD patients showed a disruption of alpha band FC to the rest of the brain. However, an adaptive extension of the language network to the right hemisphere could be observed in AD patients and was correlated with better verbal fluency. A shift of FC from alpha frequencies to theta frequencies could be observed in a memory network and was associated with better verbal memory performance. CONCLUSIONS: Not only dysfunctional but also adaptive network reorganization occurs in early AD. SIGNIFICANCE: The network mechanisms for preserved cognitive functioning may inform novel treatment strategies for AD in the future. PMID- 22781498 TI - Comparing the effects of rise time and inspiratory cycling criteria on 6 different mechanical ventilators. AB - BACKGROUND: Inspiratory rise time and cycling criteria are important settings in pressure support ventilation. The purpose of this study was to investigate the impact of minimum and maximum rise time and inspiratory cycling criteria settings on 6 new generation ventilators. Our hypothesis was there would be a difference in the exhaled tidal volume, inspiratory time, and peak flow among 6 different ventilators, based, on change in rise time and cycling criteria. METHODS: The research utilized a breathing simulator and 4 different ventilator models. All mechanical ventilators were set to a spontaneous mode of ventilation with settings of pressure support 8 cm H2O and PEEP of 5 cm H2O. A minimum and maximum setting for rise time and cycling criteria were examined. Exhaled tidal volume, inspiratory time, and peak flow measurements were recorded for each simulation. RESULTS: Significant (P < .001) differences were found when comparing minimum and maximum rise time and minimum and maximum cycling criteria for each ventilator. CONCLUSIONS: Significant differences in exhaled tidal volume, inspiratory time, and peak flow were observed by adjusting rise time and cycling criteria. This research demonstrates that during pressure support ventilation strategy, adjustments in rise time and/or cycling criteria can produce changes in inspiratory parameters. Obviously, this finding has important implications for practitioners who utilize a similar pressure support strategy when conducting a ventilator wean. Additionally, this study outlines major differences among ventilator manufacturers when considering inspiratory rise time and cycling criteria. PMID- 22781499 TI - Liver uptake of radiolabeled targeting proteins and peptides: considerations for targeting peptide conjugate design. AB - Radionuclide imaging of molecular targets for cancer therapy is likely to be a powerful tool for patient stratification and response monitoring, allowing more personalized cancer treatment. Radiolabeled proteins and peptides are a promising class of imaging probes for visualization of molecular targets in vivo. However, hepatic uptake and hepatobiliary excretion of radioactivity can decrease imaging contrast, reducing the detection sensitivity of hepatic and extrahepatic abdominal metastases, respectively. In this article, we review factors that influence the hepatic uptake of radioactivity (e.g. the chemical nature of radiocatabolites and physicochemical properties of targeting peptides and linkers) to provide input for the rational design of peptide-based imaging probes. PMID- 22781500 TI - Biomechanical analysis of the pectoralis major tendon and comparison of techniques for tendo-osseous repair. AB - BACKGROUND: Various described surgical techniques exist for the repair of pectoralis major ruptures at the tendo-osseous junction. It is unclear how these techniques restore the native properties of the pectoralis major tendon because its biomechanical properties have not been described. HYPOTHESIS: All repairs will have lower initial biomechanical profiles than the native attachment, and transosseous sutures will demonstrate improved initial biomechanical performance compared with anchors or buttons. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-four fresh-frozen cadaveric shoulders were randomized to 4 equal groups, including 3 experimental repair groups and 1 control group of intact pectoralis major tendons. The characteristics of the native anatomic footprint were recorded, and the experimental groups underwent pectoralis detachment, followed by subsequent repair. The restoration of the anatomic footprint was recorded. All specimens were tested with cyclic loading and load-to-failure protocols with load, displacement, and optical marker data simultaneously collected. RESULTS: Under cyclic loading, the intact specimens demonstrated a significantly higher secant stiffness (74.8 +/- 1.6 N/mm) than the repair groups (endosteal Pec Button [PB], 46.2 +/- 6.4 N/mm; suture anchor [SA], 45.9 +/- 8.7 N/mm; transosseous [TO], 44.2 +/- 5.5 N/mm). Measured as a percentage change, the PB and SA groups showed a significantly higher initial excursion than the intact group (PB, 24.0% +/- 11.7%; SA, 17.5% +/- 6.9%; intact, 2.2% +/- 1.0%), and the PB group demonstrated a significantly higher cyclic elongation than the intact group (PB, 7.5% +/- 2.9%; intact, 1.5% +/- 1.5%). Under load-to-failure testing, the intact group showed a significantly greater maximum load (1454.8 +/- 795.7 N) and linear stiffness (221.0 +/- 111.7 N/mm) than the 3 repair groups (PB, 353.5 +/- 88.3 N and 63.5 +/- 6.9 N/mm; SA, 292.0 +/- 73.3 N and 77.0 +/- 7.8 N/mm; TO, 359.2 +/- 110.4 N and 64.5 +/- 14.1 N/mm, respectively). All repair constructs failed via suture pulling through the tendon. CONCLUSION: The biomechanical characteristics of the transosseous repair, suture anchors, or Pec Button repair were inferior to those of the native pectoralis tendon. There was no significant difference in any of the biomechanical outcomes among the repair groups. Further refinement and evaluation of suture technique and configuration in pectoralis major repair should be considered. CLINICAL RELEVANCE: Transosseous repair, suture anchors, and endosteal Pec Buttons appear to confer similar biomechanical integrity for pectoralis major repair. Restricting early activities to thresholds below the identified failure loads seems prudent until soft tissue healing to bone is reliably achieved. PMID- 22781501 TI - Cocrystal dissociation and molecular demixing in the solid state. AB - A new cocrystal containing caffeine and theophylline was found to dissociate on heating, with caffeine and theophylline molecules spontaneously demixing and recrystallizing as separate phases, in a solid-solid transition likely driven by an increase in entropy. The morphology and composition of the resulting crystals was determined by transmission electron microscopy. PMID- 22781504 TI - Leading the way: finding genes for neurologic disease in dogs using genome-wide mRNA sequencing. AB - Because of dogs' unique population structure, human-like disease biology, and advantageous genomic features, the canine system has risen dramatically in popularity as a tool for discovering disease alleles that have been difficult to find by studying human families or populations. To date, disease studies in dogs have primarily employed either linkage analysis, leveraging the typically large family size, or genome-wide association, which requires only modest-sized case and control groups in dogs. Both have been successful but, like most techniques, each requires a specific combination of time and money, and there are inherent problems associated with each. Here we review the first report of mRNA-Seq in the dog, a study that provides insights into the potential value of applying high throughput sequencing to the study of genetic diseases in dogs. Forman and colleagues apply high-throughput sequencing to a single case of canine neonatal cerebellar cortical degeneration. This implementation of whole genome mRNA sequencing, the first reported in dog, is additionally unusual due to the analysis: the data was used not to examine transcript levels or annotate genes, but as a form of target capture that revealed the sequence of transcripts of genes associated with ataxia in humans. This approach entails risks. It would fail if, for example, the relevant transcripts were not sufficiently expressed for genotyping or were not associated with ataxia in humans. But here it pays off handsomely, identifying a single frameshift mutation that segregates with the disease. This work sets the stage for similar studies that take advantage of recent advances in genomics while exploiting the historical background of dog breeds to identify disease-causing mutations. PMID- 22781503 TI - Impact of an obesogenic diet program on bone densitometry, micro architecture and metabolism in male rat. AB - BACKGROUND: The relationships between fat mass and bone tissue are complex and not fully elucidated. A high-fat/high-sucrose diet has been shown to induce harmful effects on bone micro architecture and bone biomechanics of rat. When such diet leads to obesity, it may induce an improvement of biomechanical bone parameters in rodent.Here, we examined the impact of a high-fat/high-sucrose diet on the body composition and its resulting effects on bone density and structure in male rats. Forty three Wistar rats aged 7 months were split into 3 groups: 1 sacrificed before diet (BD, n = 14); 1 subjected to 16 weeks of high-fat/high sucrose diet (HF/HS, n = 14); 1 subjected to standard diet (Control, n = 15). Abdominal circumference and insulin sensitivity were measured and visceral fat mass was weighed. The bone mineral density (BMD) was analyzed at the whole body and tibia by densitometry. Microcomputed tomography and histomorphometric analysis were performed at L2 vertebrae and tibia to study the trabecular and cortical bone structures and the bone cell activities. Osteocalcin and CTX levels were performed to assess the relative balance of the bone formation and resorption. Differences between groups have been tested with an ANOVA with subsequent Scheffe post-hoc test. An ANCOVA with global mass and global fat as covariates was used to determine the potential implication of the resulting mechanical loading on bone. RESULTS: The HF/HS group had higher body mass, fat masses and abdominal circumference and developed an impaired glucose tolerance (p < 0.001). Whole body bone mass (p < 0.001) and BMD (p < 0.05) were higher in HF/HS group vs. Control group. The trabecular thickness at vertebrae and the cortical porosity of tibia were improved (p < 0.05) in HF/HS group. Bone formation was predominant in HF/HS group while an unbalance bone favoring bone resorption was observed in the controls. The HF/HS and Control groups had higher total and abdominal fat masses and altered bone parameters vs. BD group. CONCLUSIONS: The HF/HS diet had induced obesity and impaired glucose tolerance. These changes resulted in an improvement of quantitative, qualitative and metabolic bone parameters. The fat mass increase partly explained these observations. PMID- 22781505 TI - Silicon nanotubes from sacrificial silicon nanowires: fabrication and manipulation via embedding in flexible polymers. AB - In the present work we report a simple method to fabricate Si nanotubes (NTs) starting from the growth of self-assembled sacrificial Si nanowires that, at the same time, embeds them into a polyimide matrix, allowing a very easy manipulation of these nano-objects, including removal, transfer and positioning. Our all silicon fabrication method is completely compatible with the Si technology platform and is therefore implementable using the existing technology. Transferred NTs show good electrical contact with underlying electrodes, and relatively low resistance values have been measured. All these features demonstrate the effectiveness of the transfer method and the potentiality of the NTs in electronics. Finally, optical reflectivity of the NTs has been measured in the near UV-near IR spectral range. PMID- 22781506 TI - Exploring the role of music therapy in cardiac rehabilitation after cardiothoracic surgery: a qualitative study using the Bonny method of guided imagery and music. AB - BACKGROUND: Cardiac rehabilitation integrates physical, psychological, and vocational strategies to restore and sustain optimal health. OBJECTIVE: An innovative study using music therapy (Bonny Method of Guided Imagery and Music [BMGIM]) explored the experiences of cardiac rehabilitation participants in an outpatient setting at 2 major metropolitan teaching hospitals. METHODS: Commencing 6 to 15 weeks after cardiothoracic surgery, 6 study participants were recruited for 6 weekly music therapy (BMGIM) sessions. Qualitative analysis of the patient narrative within a semiotic framework demonstrated that patients used music therapy to spontaneously explore their recovery process. RESULTS: Five grand themes emerged: (1) looking through the frame, (2) feeling the impact, (3) spiralling into the unexpected, (4) sublime plateau, and (5) rehearsing new steps. The themes related to physical changes, adjustment after surgery, and anticipated lifestyle. CONCLUSIONS: This study demonstrates that music therapy (BMGIM) may be used to access and understand the internal recovery process of postcardiothoracic surgical patients, providing an additional clinical tool to augment the external rehabilitation process. PMID- 22781507 TI - Maintenance of changes in food intake and motivation for healthy eating among Norwegian-Pakistani women participating in a culturally adapted intervention. AB - OBJECTIVE: To investigate maintenance of changes in food intake and motivation for healthy eating at follow-up 2 data collection after a lifestyle intervention among Pakistani immigrant women. DESIGN: A culturally adapted lifestyle intervention, aiming at reducing the risk of type 2 diabetes mellitus. Data collection including FFQ and questions on intentions to change dietary behaviour was completed at baseline, right after the 7 +/- 1 month intervention (follow-up 1) and 2-3 years after baseline (follow-up 2). SETTING: Oslo, Norway. SUBJECTS: Pakistani women (n =198), aged 25-60 years, randomized into control and intervention groups. RESULTS: From follow-up 1 to follow-up 2 there was a shift from action to maintenance stages for intention to reduce fat intake (P < 0.001), change type of fat (P = 0.001), increase vegetable intake (P < 0.001) and reduce sugar intake (P = 0.003) in the intervention group. The reduction in intakes of soft drinks with sugar, fruit drinks with sugar and red meats, and the increase in intakes of vegetables and fish from baseline to follow-up 1 were maintained (significant change from baseline) at follow-up 2 in the intervention group. The intake of vegetables was higher (P = 0.019) and the intake of fruit drinks with sugar lower (P = 0.023) in the intervention group compared with the control group at follow-up 2. CONCLUSIONS: The culturally adapted intervention had the potential of affecting intentions to change food behaviour among Pakistani immigrant women long after completion of the intervention and also of leading to long-term maintenance of beneficial changes in diet. PMID- 22781508 TI - Efficacy and safety profile of dronedarone in clinical practice. Results of the Magdeburg Dronedarone Registry (MADRE study). AB - BACKGROUND: Dronedarone is a new antiarrhythmic agent that has only recently been approved for the therapy of atrial fibrillation (AF). Results regarding a broader spectrum of patients and experience accumulated in clinical practice are still very scarce. Therefore, we prospectively investigated the efficacy and tolerance of dronedarone in a real life setting. METHODS AND RESULTS: The study included 191 patients (85 women) aged 63 +/- 9.9 years with a history of paroxysmal or persistent AF. Follow-up time was 14.3 +/- 4.9 months. In patients with persistent AF, sinus rhythm was restored using electrical cardioversion prior to dronedarone administration. Each patient underwent standard ECG on a daily basis during the first 4 days of treatment, and on days 7, 30 and 90, resp. After that, the patients had a follow-up visit every three months. Creatinine, creatine kinase, and hepatic enzymes were closely monitored. Clinical history was meticulously taken at multiple follow-up visits. Dronedarone maintained sinus rhythm in 33.5% (95% CI: 27%-40%), and AF recurrence rate was high: 66.5% (95% CI: 60%-73%). Adverse effects occurred in 31.9% (95% CI: 27%-38%) of the patients and necessitated permanent discontinuation of dronedarone in 22% (95% CI: 17% 27%). CONCLUSIONS: The results suggest that dronedarone may not be superior to available antiarrhythmic agents and caution against its use as a first line therapy in AF. PMID- 22781509 TI - [Recommendations of the Portuguese Society of Rheumatology: a contribution towards improving the quality of health care]. PMID- 22781510 TI - [Clinical features of systemic sclerosis and association with antitopoisomerase-1 antibody and centromere pattern of antinuclear antibody]. AB - OBJECTIVE: To describe clinical features of patients with systemic sclerosis (SSc) and associate them with antitopoisomerase-1 antibody and centromere pattern of antinuclear antibody. METHODS: We evaluated 50 patients who met SSc screening criteria of the American College of Rheumatology, and classified as limited cutaneous SSc and diffuse cutaneous SSc. Clinical history, physical examination and laboratory tests were evaluated: cutaneous, vascular, gastrointestinal, renal, pulmonary and cardiac involvement, in addition to autoantibodies. The continuous quantitative variables, discrete quantitative and categorical variables were evaluated employing the relevant statistical tests. A P value <= 0.05 was considered statistically significant. RESULTS: The authors found that 88% of the patients were women, and 70% of the cases corresponded to the limited cutaneous form. The skin thickening assessed by the modified Rodnan skin score found as minimum of 3, and a maximum of 32, and median of 14. Raynaud's phenomenon was found in 100% of patients, skin ulcers in 56%, esophageal symptoms in 80%, interstitial lung disease in 44%, and increase in right ventricular systolic pressure in18% of the patients. Antinuclear antibodies were found in 80%, the centromere pattern in 34% and antitopoisomerase-1 in 22% of the patients. We found that 88.2% of patients with centromere pattern antinuclear antibody had limited cutaneous SSc, while 72.7% of patients with topoisomerase-1 antibodies had diffuse cutaneous SSc. CONCLUSION: The clinical features of this population of patients with SSc are similar to results in the literature, as well as the association with the autoantibodies evaluated. PMID- 22781511 TI - CoReumaPt protocol: the Portuguese cohort of rheumatic diseases. AB - INTRODUCTION: Rheumatic diseases (RD) are conditions with a variety of clinical manifestations and prognosis influenced by several factors. Cohorts and registries have been already established in some countries and have contributed to important knowledge about the disease course and the long-term outcomes of RD. This paper introduces the CoReumaPt project and sets the first step towards the creation of a prospective cohort study including the main RD occurring in the Portuguese population. CoReumaPt will allow outcomes research of chronic RD and the assessment of factors influencing the development and progression of RD. It will also allow to further evaluate the economic impact and the burden of RD in Portugal. CoReumaPt will be linked to Reuma.pt, the National Register of Rheumatic Diseases from the Portuguese Society of Rheumatology. METHODS: An open cohort will be created, initially composed by the randomly selected population of the crosssectional National Epidemiological Rheumatic Diseases study (EpiReumaPt) and afterwards by other sources, namely through self- and physician's referral. Follow-up with annual self-administered questionnaires will be performed, in order to systematically collect and analyze outcomes of interest, mainly patient reported outcomes. Data concerning less frequent assessments, such as radiographs and biomarkers, will also be assembled. CONCLUSIONS: CoReumaPt will be a valuable resource for scientific research and will deliver pivotal information to improve public health policies concerning the prevention and the management of RD in Portugal. PMID- 22781512 TI - 2011 Portuguese recommendations for the use of biological therapies in patients with psoriatic arthritis. AB - OBJECTIVE: To develop recommendations for the treatment of psoriatic arthritis (PsA) with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. A draft of the recommendations was first circulated to all Portuguese rheumatologists and their suggestions were incorporated in the draft. At a national meeting the recommendations were discussed and all attending rheumatologists voted on the level of agreement for each recommendation. A second draft was again circulated before publication. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with PsA. Specific recommendations were developed for several disease domains: peripheral arthritis, axial disease, enthesitis and dactylitis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with PsA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated. PMID- 22781513 TI - Portuguese recommendations for the use of biological therapies in patients with axial spondyloarthritis--December 2011 update. AB - OBJECTIVE: To develop recommendations for the treatment of axial spondyloarthritis with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. A draft of the recommendations and supporting evidence was first circulated to all Portuguese rheumatologists and their suggestions were incorporated in the draft. Secondly, at a national meeting the recommendations were presented, discussed and revised. Finally, the document resulting from this meeting was again circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the recommendations. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with axial spondyloarthritis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with axial spondyloarthritis should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated. PMID- 22781514 TI - Portuguese recommendations for the use of biological therapies in children and adolescents with juvenile idiopathic arthritis--December 2011 update. AB - OBJECTIVE: To update the Portuguese recommendations in order to assist the rational and safe prescribing of biological therapies in children and adolescents with Juvenile Idiopathic Arthritis (JIA) as more evidence and experience with these drugs are available. METHODS: The recommendations were formulated by Rheumatologists and Pediatricians, with experience in Pediatric Rheumatology, based on literature evidence and consensus opinion. The evidence was sought through a MEDLINE search. The retrieved results were discussed and a set of recommendations proposed. All propositions were extensively debated and the final recommendations formulated. RESULTS: A consensus was achieved regarding the eligibility, response criteria, maintenance of biologic thera py, and procedures in case of non-response. Also, specific recommendations concerning safety procedures before and while on biologic therapies were formulated. CONCLUSIONS: Thirteen recommendations for guidance biological therapy in children and adolescents with JIA were developed using both evidence-based and expert consensus. These recommendations will be updated as more evidence becomes available and more biological therapies are licensed. PMID- 22781516 TI - Definitive bilateral adrenal failure in antiphospholipid syndrome. AB - Antiphospholipid antibodies may signal the formation of vascular thrombi in the Antiphospholipid syndrome (APS). A rare complication of APS is adrenal insufficiency resulting from venous thrombus followed by hemorrhagic infarction. We describe the case of a 42-year-old male with APS presenting with vomiting and abdominal pain. Through laboratory and imaging diagnostic exams, we confirmed the diagnosis of bilateral adrenal hemorrhage and subsequent adrenal failure. We also conducted a search of literature associating bilateral adrenal thrombosis to APS, and describe the two pathological mechanisms most often cited to explain this phenomenon. To our knowledge, this is the first Portuguese case of adrenal insufficiency due to APS-associated bilateral adrenal hemorrhage. PMID- 22781515 TI - [Septic arthritis and gout--a case report]. AB - The authors describe a 54 year-old male patient, admitted after presenting in the emergency room with acute oligoarthritis affecting the shoulders and right tibiotarsal and sternoclavicular joints, with a week's duration. He was non febrile and related a purulent discharge from the stump of a traumatic amputation of the left thumb, starting a few days prior to the presenting complaints. There was a previous history of gouty arthritis and moderate alcoholism. Lab work revealed an elevation of the acute phase markers, with marked neutrophilia. Upon admittance, the patient underwent arthrocentesis, revealing a purulent discharge with sodium monourate crystals, which cultured positively for meticillin sensitive Staphylococcus aureus. Besides antibiotherapy, on Day 5 the patient presented with a cervical abscess with extension to mediastinum; the abscess was drained by a cardiothoracic surgeon, and the right sternoclavicular and first costochondral articulations were found to be destroyed. The authors note that, although it is a rare occurrence septic arthritis can coexist with gout, while discussing the possible mecanisms of this association, as well as particular details of the clinical case presented. PMID- 22781517 TI - Lupus erythematosus panniculitis in children and adolescents. AB - INTRODUCTION: Lupus erythematosus panniculitis (LEP) or lupus erythematosus profundus is a rare form of chronic cutaneous manifestation affecting both adults and pediatric patients. The prevalence of this manifestation was seldom reported in juvenile systemic lupus erythematosus (JSLE). CASE REPORTS: From January 1983 to December 2010, 5,506 patients were followed at the Pediatric Rheumatology Unit of our University Hospital and 278 (5%) of them met the American College of Rheumatology classification criteria for JSLE. Two (0.7%) of them had LEP at JSLE onset. These two cases had tender deep inflammatory subcutaneous nodules or plaques at the time of diagnosis, and the histopathologic pattern evidenced lobular or mixed panniculitis with lymphocytic inflammatory cells of the fat lobule. Treatments for LEP included mainly antimalarials, systemic corticosteroids and sunscreen protection. One male patient required thalidomide and immunosuppressive drugs, including mycophenolate mofetil, cyclosporin and intravenous cyclophosphamide. However, skin lesions improved only after rituximab treatment. DISCUSSION: LEP was rarely observed in our cohort of JSLE patients as the first lupus manifestation. Anti-CD20 monoclonal antibody therapy may be an option for refractory LEP treatment in children. PMID- 22781518 TI - [Complex Regional Pain Syndrome--an unusual etiology]. AB - Complex Regional Pain Syndrome type 1 is characterised by neuropathic pain associated with autonomic dysfunctions. It frequently appears after major or minor trauma and more rarely may originate from conditions that compromise the central nervous system. Although few treatments have shown to be effective, their institution at an early stage is decisive for their success. For this reason it is important to ensure timely recognition of this clinical entity, attempting to identify its cause and the predominant underlying physiopathological mechanisms whenever possible. The authors describe a case of complex regional pain syndrome type 1, emphasising the rarity of this clinical situation in association with a Parkinsonian Syndrome. PMID- 22781519 TI - Childhood hypophosphatasia with myopathy: clinical report with recent update. AB - Hypophosphatasia is a rare genetic disease with low tissue nonspeficic alkaline phosphatase activity (TNSALP), due to ALPL gene mutation. There are 6 clinical forms. Childhood form is caractherized by short stature, premature loss of decidous teeth and diffuse bone pain associated with a pathological bone fracture in the past. Laboratory findings present low serum level of alkaline phosphatase and high levels of serum and urinary extracelular metabolytes. It is described a case report of a 34 years old woman with previous diagnosis of childhood hypophosphatasia, caryotype 46,XX, and molecular screening for the gene ALPL with a c.1426>A p.E476K mutation, who complained of proximal muscular weakness intensified with the cold weather, exercise, and a waddling gait. The electromyography was compatible with myopathy but the muscle biopsy was normal. The serum creatine kinase levels were normal, as well as the others muscle enzymes. Clinical and laboratory/ /imaging dissociation is frequent in other metabolic bone diseases as osteomalacia. The rarity of this case of childhood hypophosphatasia with "de novo" non-progressive myopathy of the lower limbs, justified a case report with literature revision. PMID- 22781520 TI - [Multiple exostoses]. PMID- 22781521 TI - [Low-impact humeral fracture revealer of chondrosarcoma: a case of exuberant tissue destruction]. PMID- 22781522 TI - Idiopathic peripheral ulcerative keratitis with good response to methotrexate. PMID- 22781523 TI - [Pediatric anesthesia: humanization and comfortability]. PMID- 22781524 TI - [An audit of perioperative fluid management and electrolyte monitoring in children undergoing surgery for scoliosis]. AB - OBJECTIVE: To audite and compare the perioperative practices of intravenous fluids and electrolyte & glucose monitoring in children undergoing operations for scoliosis in 2008, 2010, prior to and after the publication of guideline in 2009. METHODS: Retrospective audit was conducted at Peking Union Medical College Hospital, a tertiary referral teaching hospital in Beijing, China. Children under 14 years old with scoliosis treated surgically in 2008 and 2010 were recruited. The following data were collected from medical files: age, gender, weight, duration of hospitalization, concurrent illness, operation, anesthesia, fluid prescribed during perioperative fasting period, electrolyte monitoring and postoperative pain control, etc. RESULTS: Among 235 American Society of Anesthesiologists (ASA) I-II cases, 75 children received dextrose 5% or saline 0.9% during the preoperative fasting period. Intraoperatively, the anesthesiologists preferred dextrose 5% or saline 0.9% in children under 6 years old (n = 15, 2008; n = 15, 2010) and Ringer's solution in those aged 6 - 14 years (n = 84, 2008; n = 94, 2010) and hypotonic fluid was not used. And 82.3% and 94.3% of them received electrolyte examinations preoperatively. The electrolyte results were unavailable postoperatively in 27/122 (in 2008) and 13/113 (in 2010) and serum electrolytes were not assessed before fluid treatment postoperatively. Electrolytes were monitored only once in 82.3% (in 2008) and 70.5% (in 2010) patients. Compared with the preoperative concentration of sodium ion, the mean decrease was approximately 2.0 mmol/L at Day 1 postoperation. Hyponatremia at Day 1 postoperation in 2010 was more common than that in 2008 (26.2% vs 23.6%; P = 0.044). But no significant difference existed between the incidence of hyperglycemia of the same day in 2008 and that in 2010 (P = 0.306). CONCLUSION: Compared with that in 2008, our recent practice of intravenous fluid prescription and electrolyte monitoring is ill-consistent with the recommendations in 2009. Implementation of optimal perioperative fluid management is warranted. PMID- 22781525 TI - [Application of ultrasound guidance for ilioinguinal or iliohypogastric nerve block in pediatric inguinal surgery]. AB - OBJECTIVE: To evaluate the efficacy of ultrasound guidance for ilioinguinal or iliohypogastric nerve block in pediatric outpatients undergoing inguinal surgery. METHODS: The present study was approved by the ethics committee of our hospital. One hundred children with ASA status I, aged 4 - 8 years old, scheduled for unilateral inguinal surgery were randomly divided into ultrasound group (Group U) and traditional group (Group T) (n = 50 each). Upon entering operation room, they were monitored by electrocardiography (ECG), heart rate (HR) and oxygen saturation (SpO(2)). After an induction of general anesthesia, intravenous access was established and laryngeal mask inserted with spontaneous breathing. Intraoperative anesthesia was maintained with 2% sevoflurane in 50% nitrous oxide with 50% oxygen. Children in Group U received an ilioinguinal or iliohypogastric block under ultrasonic guidance with a mixture of 0.8% lidocaine and 0.25% levobupivacaine at 0.2 ml/kg while those in Group T performed according to the traditional method of anatomical localization with the same local anesthetic at 0.3 ml/kg. During surgery, the vital signs of HR, respiratory rate (RR), SpO(2), partial pressure of end-tidal carbon dioxide (P(ET)CO(2)) and exhaled sevoflurane concentration were recorded. Additional intraoperative analgesic requirements were recorded. Face legs activity cry consolability (FLACC) score was used to assess the pain score postoperatively at recovery time, 2 and 4 h postoperation respectively. If the pain score was above 3, the child received acetaminophen rectally. The number of postoperative rectal acetaminophen was recorded. The degrees of parental satisfaction were investigated at 2 and 4 h postoperation. Intra-or postoperative adverse events were also recorded. RESULTS: HR at skin incision and sac traction in Group U was significantly lower than those in Group T (P < 0.05). Six children (12%) needed to increase inhaled sevoflurane concentration during operation in Group U versus 17 (34%) in Group T (P < 0.05). The pain score at recovery time, 2 and 4 h postoperation in Group U was significantly lower than those in T group (P < 0.05). Only 4 children (8%) needed postoperative rectal acetaminophen in Group U versus 13 (26%) in Group T (P < 0.05). The degree of parental satisfaction at 2 h postoperation was significantly higher in Group U than that in Group T (P < 0.05). One case in Group T had needle puncturing into blood vessels. No other adverse event was observed in two groups. CONCLUSION: The method of ultrasonic guidance for ilioinguinal or iliohypogastric nerve block is both feasible and effective. It can not only enhance the effect of nerve block, reduce the occurrences of complications, lower the quantity of local anesthetic and alleviate the medicinal toxicity. PMID- 22781526 TI - [Effect of dexmedetomidine on postoperative analgesia and sedation in pediatric patients undergoing cleft lip and palate repair]. AB - OBJECTIVE: To explore the effect of different doses of dexmedetomidine on the sedation of recovery period and the postoperative early pain scores in pediatric patients undergoing cleft lip and palate repair. METHODS: A total of 100 American Society of Anesthesiologists (ASA) I-II pediatric patients undergoing cleft lip and palate repair were randomly divided into 5 groups (D1, D2, D3, D4 and C, n = 20 each). Groups D1-D4 received a continuous pump infusion of dexmedetomidine at 0.25, 0.5, 0.75, 1.0 ug * kg(-1)* h(-1) respectively for 1 h before the completion of operation. Then an intravenous injection of 1 ug/kg was prescribed over 10 min as a loading dose. Group C, taken as control, received an equal volume of normal saline. Propofol 2 mg/kg was added for the occurrence of emergence agitation. Mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), partial pressure of end-tidal carbon dioxide (P(ET)CO(2)), Riker sedation-agitation scale, times of additional propofol requirements, times of additional artificial ventilation, extubation time, discharge time, side effects and face, legs, activity, cry and consolability (FLACC) scale were observed and recorded. RESULTS: The Riker sedation-agitation scale were 5.3 +/- 0.9, 4.3 +/- 0.8, 3.5 +/- 0.8, 2.6 +/- 0.6 and 6.1 +/- 0.7, times of additional propofol requirements were 4.7 +/- 1.7, 2.5 +/- 1.4, 0.8 +/- 0.9, 0.1 +/- 0.4 and 5.7 +/- 0.7 in groups D1, D2, D3, D4 and C respectively. In short, group D4 ~ group D3 < group D2 < group D1 < group C (P < 0.05). As compared with group D4, the extubation time and discharge time significantly increased in groups D1, D2, D3 and C (P < 0.05). The FLACC scales in groups D2, D3 and D4 were lower than those in groups D1 and C. Side effects: 2 cases developed sinus bradycardia in group D4 and heart rate returned to normal after treatment. CONCLUSION: At a load dosage of 1 ug/kg and a maintenance dosage of 0.75 ug * kg(-1)* h(-1), dexmedetomidine shows excellent effects on the recovery period of cleft lip and palate repairing in pediatric patients. The FLACC scale decreases with fewer side effects, but extubation time and discharge time increase. PMID- 22781527 TI - [A comparison of ultrasonography versus traditional approach for caudal block in children]. AB - OBJECTIVE: To apply ultrasonic technology in positioning and monitoring for pediatric caudal blocks and compare it with traditional landmark approach and Swoosh test. METHODS: After obtaining the approval of hospital ethics committee and written parental informed consent, a total of 102 American Society of Anesthesiologists (ASA) I-II pediatric patients aged from 1 month to 8 years and scheduled for urologic or perineal surgery were recruited. Patients were randomly divided into 2 groups: ultrasound group (n = 52) and control group (n = 50). The sites of sacral cornu and sacral hiatus were determined by ultrasonic imaging or classic method of anatomical surface landmarks. Patients of two groups were punctured according to the scheduled site. Local anesthetic was injected slowly into caudal space after a successful caudal puncture and the positive reaction in caudal space was monitored simultaneously by ultrasound and classic swoosh test. The observational results and relevant date were recorded. RESULTS: In ultrasound and control groups, the number of puncture attempts was 1.10 +/- 0.30 vs 1.56 +/- 0.63, the duration of puncture (1.40 +/- 0.39) vs (3.23 +/- 1.23) min, the success rate at the first puncture attempt 90.4% vs 66% and the total puncture success rate 100% vs 92% respectively. After the injection of local anesthetic, the positive reaction rate of ultrasonography and swoosh test was 97.96% vs 62.24% respectively. All of above results in ultrasound group were superior to those in control group or with classic test. And the difference had statistical significance (P < 0.01). CONCLUSION: Ultrasonic positioning and monitoring for pediatric caudal block is both scientific and reasonable. The positioning detected by ultrasonic imaging is accurate and the monitoring results of ultrasound are reliable. It is obviously superior to traditional method and has clinical application values for caudal block in children. PMID- 22781528 TI - [Assessment and management of difficult airways in neonates with Pierre Robin sequence]. AB - OBJECTIVE: To assess the difficult airways preoperatively in neonates with Pierre Robin sequence (PRS). METHODS: A total of 18 newborn PRS with difficult intubation were evaluated with the assessment grade. The scores were based upon clinical observation, weight gain, airway obstruction and Cormack-Lehane classification. RESULTS: A total of 14 neonates (77%) had medium (n = 8) and severe (n = 6) airway obstruction. And 89% (n = 16) failed to display glottis and unsuccessful tracheal intubation (50%). CONCLUSION: The assessment practice of clinical observation, weight gain, airway obstruction and Cormack-Lehane classification may help to identify the difficult airways in neonates with PRS. PMID- 22781529 TI - [Relationship between sorafenib-associated hand-food skin reaction and efficacy in treatment of advanced hepatocellular carcinoma]. AB - OBJECTIVE: To investigate the link between the antitumor efficacy of sorafenib and its cutaneous side effects in advanced hepatocellular carcinoma (HCC). METHODS: We retrospectively analyzed the incidence of hand-foot skin reactions (HFRS) of 51 patients with advanced HCC who treated by sorafenib combined with transcatheter arterial chemoembolization (TACE), comparing tumor disease control rate (DCR), median progression free survival (mPFS) and median overall survival (mOS) in the different severity HFRS groups. The Cox proportional hazard model was applied to the multivariate survival analysis for the PFS. RESULTS: Fifty-one HCC patients treated with sorafenib combined with TACE were included in this study. 13/51 without HFRS (grade 0), 38/51 developed at all grade 1-3, 27 developed at grade 1-2, 11 developed at grade 3. The DCR were 38.5%, 70.4% and 90.9% in the three groups (P < 0.05). Group grade 0 vs grade 1-3, P = 0.031, the difference had statistical significance. Group grade 1-2 vs grade 3, P = 0.352, the difference had no statistical significance. The mPFS were 2.8 months (95%CI 1.6 - 4.0), 4.5 (95%CI 1.3 - 7.7) months and 12.8 (95%CI 3.7 - 21.9) months (P < 0.05), group grade 0 vs grade 1-2, P = 0.019, HR (hazard ratio): 2.8 (95%CI 1.3 - 6.3), P = 0.010, group grade 0 vs grade 3, P < 0.01, HR 6.6 (95%CI 2.3 - 19.0), P < 0.01, group grade 1-2 vs grade 3, P = 0.054; the three groups' mOS were 8.5 months (95%CI 5.9 - 11.1), 13.0 (95%CI 10.1 - 15.9) months and 25.4 months, P < 0.05, there were statistically significant differences between the any two groups. CONCLUSIONS: HFRS should be closely monitored in HCC patients treated with sorafenib in relation to its potential role as a surrogate marker of efficacy, but it has yet to be demonstrated whether the efficacy increasing with the severity of HFRS or not. PMID- 22781530 TI - [Clinical analysis of adult primary bloodstream infection]. AB - OBJECTIVE: Evaluate the microbiological and epidemiological characteristics of primary bloodstream infections as well as the associated patients' clinical features at Peking Union Medical College Hospital. METHOD: Microbiological and clinical data of the adult patients with primary bloodstream infections during January 1, 2008 and December 31, 2009 were retrospectively collected and evaluated. Pearson chi(2) test was used to compare the difference between proportions and Logistic regression was used in multivariate analysis. RESULT: Five hundred and eighty-six strains of microbes were isolated from 494 adult patients with primary bloodstream infections. There were 80 patients with polymicrobial primary bloodstream infection of the 586 isolates, coagulase negative staphylococci (175, 29.9%) was the most common, followed by Escherichia coli (93, 15.9%), Enterococcus species (60, 10.2%), Streptococcus species (41, 7.0%), and Staphylococcus Aureus (39, 6.7%). Central-line was the leading suspected infective source among the suspected infective source involving 108 (18.4%) isolates. Excluded the 108 isolates with suspected sources, 77 (45.3%) out of 167 patients with the primary bloodstream infections caused by coagulase negative staphylococci or Staphylococcus Aureus had a central-line, with a higher proportion of the patients with a central-line than the patients with bloodstream infection caused by other pathogens (chi(2) = 10.419, P = 0.001). One hundred and fourteen patients died during hospitalization, with the crude mortality rate 23.0%. Fifty-nine patients (11.9%) died due to primary bloodstream infection. The patients with polymicrobial bloodstream infection were with a higher attributable mortality (OR = 2.159;95%CI 1.165 - 4.002; chi(2) = 6.194, P = 0.013). In the multivariate analysis, the independent risk factors of crude mortality rate to primary bloodstream infections were elderly patients, central neurological disorder, mechanical ventilation, and reservation a central-line. CONCLUSION: The most common microbe causing primary bloodstream infections was G+ cocci. Polymicrobial primary bloodstream infection added risk to attributable in hospital fatality ratio. Elderly patients, neurological disorder, reservation of central-line, and mechanical ventilation were the independent risk factors of crude in-hospital fatality ratio. PMID- 22781531 TI - [Gamma event-related synchronization analysis: a new method for cortical function mapping]. AB - OBJECTIVE: To localize the sensory motor cortex of human brain by analyzing the power change in Gamma band (> 60 Hz) of electrocorticography (ECoG) data. METHODS: Eight patients with intractable epilepsy underwent temporary placement of subdural electrodes. After surgery, sensory evoked potential (SEP), electrocortical stimulation (CES) and event-related synchronization analysis of Gamma band (Gamma ERS analysis) were performed to reduce the risk of complications. The results of Gamma ERS analysis were compared with those of SEP and CES. RESULTS: The results of Gamma ERS analysis had 80.7% electrodes fitting perfectly those of CES and SEP. And the percentage reached 92.3% if electrodes were superimposed or added adjacently. CONCLUSION: The Gamma ERS analysis is a new sensitive and precise method for cortical function mapping. PMID- 22781532 TI - [Comparison of percutaneous versus open monosegment instrumentation in the treatment of incomplete thoracolumbar burst fracture]. AB - OBJECTIVE: To compare the safety and efficacies of traditional open versus percutaneous monosegmental pedicle screw fixation in the treatment of incomplete thoracolumbar spinal fracture. METHODS: A retrospective analysis was conducted for 44 inpatients with a diagnosis of incomplete thoracolumbar spinal fracture (AO classification: A3.1 and A3.2) undergoing monosegmental pedicle instrumentation (MSPI) from September 2008 to January 2011. There were 24 cases in percutaneous group and 20 cases in traditional open group. The mean operative duration, blood loss, blood drainage, visual analogue scale/score (VAS) and vertebral kyphotic angle at pre- and post-operation were evaluated. RESULTS: No significant differences existed in operative durations between two groups (P > 0.05). Significant differences between two groups were observed in terms of intra operative blood loss and VAS scores at Week 1 postoperation (P < 0.05). There were no significant differences in VAS score preoperation, 1 year postoperation or pre-and post-operative vertebral kyphotic angle (P > 0.05). No complications of iatrogenic neurological injury or hardware failure occurred. CONCLUSION: The application of percutaneous monosegment pedicle instrumentation in the treatment of thoracolumbar fractures in type of A 3.1 and A 3.2 is both feasible and safe. Its postoperative therapeutic effect is comparable to that of traditional open monosegmental fixation. PMID- 22781533 TI - [Combination of central venous-to-arterial PCO2 difference with central venous oxygen saturation to guide the shock resuscitation]. AB - OBJECTIVE: Central venous oxygen saturation (ScvO2) is a useful therapeutic target in septic shock and high-risk postoperative patients. We tested the hypothesis that central venous-to-arterial carbon dioxide difference (DeltaPCO(2)) combine with ScvO2 to guide shock resuscitation is better than ScvO2 only. METHODS: A retrospective study was conducted for 93 septic shock and high-risk postoperative patients. They underwent resuscitation through early goal directed therapy. We calculate whether there were correlations between the DeltaPCO(2) and tissue perfusion index or blood flow index, including the beginning of resuscitation (T0) and after 6 hour resuscitation (T6). They were divided into 4 groups according to DeltaPCO(2) and ScvO2. Then the clearance of lactate was compared between the groups. RESULTS: No correlation existed between DeltaPCO(2) and tissue perfusion index. But there was some correlation between DeltaPCO(2) and the indices of blood flow such as CO, ScvO2 and clearance of lactate. At T0, the correlation (r) between DeltaPCO(2) and cardiac index was 0.858 (P = 0.029) and the correlation between DeltaPCO(2) and ScvO2 -0.403 (P = 0.000). At T6, the correlation (r) between DeltaPCO(2) and ScvO2 was -0.363 (P = 0.000) and the correlation between DeltaPCO(2) and clearance of lactate -0.314 (P = 0.002). After continuous 6-hour resuscitation, there was significant difference in clearance of lactate between the groups. The clearance of lactate was the highest in the group of patients achieving the goals of both ScvO2 > 70% and DeltaPCO(2) < 6 mm Hg. We further analysis the DeltaPCO(2) < 6 mm Hg and ScvO2 > 70% subgroup and found that the 6 h lactate clearance rate were statistically significant difference. CONCLUSION: The combination of DeltaPCO(2) and ScvO2 may guide the shock resuscitation. It helps identify the inadequately resuscitated when the ScvO2 goal is reached. PMID- 22781534 TI - [Comparison of mental rotation ability for depressive disorder and schizophrenia]. AB - OBJECTIVE: To compare the mechanism of depressive disorder and schizophrenia' mental rotation ability so as to provide specific objective clinical indicators for identifying mental illness. METHODS: Thirty depressive disorder (15 males, 15 females), 30 schizophrenia (15 males, 15 females) and 28 healthy participants (14 males, 14 females) were tested to perform mental rotation tasks with the letter F and R graphics. The subjects were required to decide whether the stimulus was a normal or a mirror version of an alphabet letter presented in different views and angular orientations. The mouse left key was pressed for a normal and the mouse right button for a mirror. RESULTS: (1) Error rate: As compared with the normal control group (normal: 29% +/- 10%, mirror: 32% +/- 3%), the normal error rate was significantly higher while the mirror error rate significantly lower in depressive disorder (normal: 31% +/- 13%, mirror: 22% +/- 4%, P < 0.01); the normal error rate was significantly lower while the mirror error rate significantly higher in schizophrenia (normal: 27% +/- 9%, mirror: 42% +/- 2%, P < 0.01). (2) Normal reaction rate: As compared with the normal control group (50% +/- 9%), the normal reaction rate was significantly lower in depressive disorder (38% +/- 12%, P < 0.01) and significantly higher in schizophrenia (60% +/- 9%, P < 0.01). (3) Response time: As compared with the normal control group (normal (602 +/- 25) ms, mirror (606 +/- 14) ms), the normal and mirror response durations were both significantly longer in depressive disorder(normal (653 +/- 23) ms, mirror (714 +/- 13) ms, P < 0.01) while significantly shorter in schizophrenia (normal (571 +/- 18) ms, mirror (587 +/- 11) ms, P < 0.01). CONCLUSION: Normal mental rotation ability is severely impaired in depressive disorder, but its mirror counterpart becomes compensated. In schizophrenia, mirror mental rotation ability is severely impaired, but its normal counterpart becomes compensated. It hints that normal and mirror rotation ability may be interchangeable so as to serve as a state index. The impairment of mental rotation ability impaired can be used as specific objective clinical indicators of identifying mental illness. PMID- 22781535 TI - [Efficacy and safety of tandospirone in the treatment of patients with anxiety disorder]. AB - OBJECTIVE: To explore the efficacy and safety of tandospirone for adolescents with anxiety disorder. METHODS: In this multicenter open-label 12-week study, a total of 169 adolescents met the criteria of DSM-IV for anxiety disorder were treated with flexible dose of tandospirone. The effects and safety of treatment were assessed by the Hamilton anxiety scale (HAMA), state-trait anxiety inventory (STAI), clinical global impression (CGI) and side effects at baseline and Weeks 2, 4, 8 and 12. RESULTS: In 151 cases completing the 12-week treatment, the scores of HAMA decreased by 18% +/- 12%, 38% +/- 16%, 54% +/- 20% and 63% +/- 17% at Weeks 2, 4, 8 and 12. Significant reductions in HAMA scores were seen at Weeks 2-12 (P < 0.01) and marked improvement appeared in 81.5% cases at Week 12 (reduction rate of HAMA: 50%). At Week 12, the HAMD(17) scores were markedly lower versus baseline (7 +/- 2 vs 13 +/- 3, P < 0.01). Adverse effect of tandospirone was scarcely found (9.9%). CONCLUSION: Tandospirone is an effective and safe anti-anxiety drug for adolescents. PMID- 22781536 TI - [Correlation of surgical timing and prognosis for ruptured intracranial aneurysms]. AB - OBJECTIVE: To explore the correlation between surgical timing and clinical prognosis for ruptured intracranial aneurysms. METHODS: A series of 187 patients with intracranial aneurysm treated surgically at our department were analyzed retrospectively. Among them, 101 patients received an average follow-up period of 9 months (range: 6 - 14). Timings of operation that might affect the clinical efficacies of microsurgery were analyzed. The modified Rankin scale (mRS) of discharge and the corresponding follow-up mRS were all analyzed. RESULTS: Timing of operation was negatively correlated with mRS of hospital discharge (P < 0.05), but it had no correlation with follow-up mRS (P > 0.05); patients whose discharge mRS were 1, 2, 3 or 4 had better long-term efficacies (P < 0.05) while those with a discharge mRS of 5 fare worse (P > 0.05). CONCLUSION: The short-term efficacy of early microsurgery for intracranial aneurysms is worse than those of medium and late microsurgery. But no obvious differences exist between the long-term efficacies of early, medium and late microsurgery. The patients whose discharge mRS were 1, 2, 3 or 4 have better long-term efficacies. PMID- 22781537 TI - [Effects of blueberry on hepatic fibrosis and ultrastructural of hepatocytes in rats]. AB - OBJECTIVE: To observe the effects of blueberry on rat with hepatic fibrosis and ultrastructural. of hepatocytes. METHODS: Sixty (60) healthy Wistar rats were randomly divided into six groups: normal control group (group A), hepatic fibrosis model group (group B), blueberry at low, middle and high concentration groups (group C, D, E), Fu-Fang-Bie-Jia-Ruan-Gan tablet group (group F). The hepatic fibrosis model of rat was established by intraperitoneal injection of porcine serum once daily for 12 weeks. Simultaneously, rats in groups C-F were respectively perfused with blueberry juice or Fu-Fang-Bie-Jia-Ruan-Gan tablet for 12 weeks except for the normal control group which accepted saline alone. Upon terminal sacrifices of all rats at the end of the twelve weeks. Pathology of hepatic tissue was evaluated by hematoxylin-eosin (HE), Masson staining and transmission electron microscope. Liver index were measured. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were examined. Activities of superoxide dismutase (SOD), the contents of malondialdehyde (MDA), hydroxyproline (Hyp) and reduced glutathione (GSH) in liver homogenates were determined. RESULTS: Refer to the serum levels of ALT and AST, there is no significant difference existed in all groups (P > 0.05). Activities of SOD, the contents of GSH in liver homogenates of group D and E were significantly higher than those of group B(P < 0.05), while liver index, the contents of Hyp, MDA in liver homogenates were significantly lower than those of group B (P < 0.05). Compared with the group B, the pathological stages of hepatic fibrosis in group D and E were significantly reduced (P < 0.05), the expression of collagen were decreased, ultrastructural alterations were markedly improved. CONCLUSION: Blueberry may have certain preventional protective effects on porcine serum induced rat hepatic fibrosis and exhibit certain protective effects on organelles of hepatocytes (such as mitochondria), especially in middle and high does of blueberry. Its mechanism is probably related to increase the ability of antioxidant stress by increasing SOD activity and GSH content and reducing MDA content. PMID- 22781538 TI - [Effects of obesity on the lipid and glucose metabolism in female rats]. AB - OBJECTIVE: To investigate the effects of obesity on the lipid and glucose metabolism in female rats. METHODS: The litter size was adjusted to 4 pups per litter for the small litter (SL, treatment group) and 12 neonates per dam in the normal litter (NL, controls) at postnatal day 0. Body weights were measured weekly. At the age of 6 weeks, bilateral ovariectomy was performed. The blood levels of free fat acid, triglyceride, total cholesterol, free blood glucose and free insulin were evaluated. The muscular expression of AMP-activated protein kinase was detected by immune staining. RESULTS: As compared to normal litters, the levels of fat acid, triglyceride, total cholesterol, free blood glucose and free insulin significantly increased. The muscular activity of AMP-activated protein kinase decreased. All difference were statistically significant (P < 0.05). CONCLUSION: Obesity in early life has obvious effects on the lipid and glucose metabolism in female rats. PMID- 22781539 TI - [Networks in cognitive research]. AB - This review paper starts from discussing two models of network research: one starting from general networks, the other starting from the Ego. Ego based researches are characterized starting form the model of Dunbar as presenting networks of different size and intimacy, both in real and virtual networks. Researches into the personality determinants of networks mainly shows the effects of extroversion. The future of network research indicates a trend towards relating personal, conceptual, and neural networks. PMID- 22781540 TI - [Body-mind unity in tandem hypnotherapy]. AB - INTRODUCTION: The new bodymind theory describes unity of body and mind as a quantum process, which can go back to embryonic period of life. METHOD: Authors have worked out tandem hypnotherapy method regarding bodymind theory. Tandem has two meanings: (1) a multi-seater bicycle, (2) a mosaic word: Touch of Ancient and New generations with a Dialogue Experiencing Oneness of Minds (TANDEM). Hypnotherapy, psychodrama, family therapy, Hellinger's systemic-phenomenological approach, and, the holding-therapy can be viewed as precedents of the method. More than two persons in a physical closeness touching each other take part in therapy: (1) patient(s), (2) one or more co-therapists; one or more antagonists (in the latter case is of hypnodrama), (3) therapist, who is responsible to take the tandem of patient(s) and co-therapist(s) to trance, while (s)he keeps distance securing neutrality. RESULTS: The method will be illustrated with some case-vignettes. DISCUSSION: Sensory-motor level of development is supposed by the authors as stemmed from fetal period of life. It is suggested to be paralled to associative mode of experiencing, in which object and subject can't be viewed as differenciated from each other resulting unity or oneness experience. The most effective stimulus of associative mode of experiencing is regarded to be physical closeness and touching, which are seen in intimate situations. That is the reason why fundamental rules of therapeutic touching are to be kept. CONCLUSION: The new method can be viewed as a form of bodypsychotherapy having possibilities to resolve pathological consequences of either fetal or intergenerational traumas. PMID- 22781541 TI - [Comparing the comorbidity of attention-deficit/hyperactivity disorder in childhood and adolescence]. AB - BACKGROUND: International researches found that comorbid psychiatric diagnoses are present in more than two-thirds of attention-deficit/hyperactivity disorder (ADHD) cases, and the patterns of comorbidity are influenced by developmental aspects. The aim of this study is to compare the comorbid diagnoses with ADHD on a Hungarian sample between a children and an adolescents. METHODS: Children and adolescents (under the age of 18) with ADHD according to the Mini International Neuropsychiatric Interview Kid, hospitalized for the first time to Vadaskert Psychiatric Hospital for Children and Adolescents were included in the study. The study sample was divided into two groups: children (3-12 years) and adolescents (13-18 years). Descriptive statistics, Chi-square test and independent sample t test were applied. RESULTS: The most common comorbid diagnoses with ADHD were oppositional defiant disorder, conduct disorder and suicide behavior in both age groups, as well as manic episode in the child group and generalized anxiety disorder in the adolescent group. In the adolescent group the number of comorbid diagnoses with ADHD (mean number of diagnoses= 4.30; SD=2.84) was significantly higher than in the child group (mean number of diagnoses=2.61; SD=1.73) (t= 3,726; df=50,202; p<0,001). Comparing the prevalence of comorbid disorders between the two age groups, we did not found any diagnosis which was significantly more common in the child group than in the adolescent group, while major depressive disorder, suicide behavior, dysthymic disorder, alcohol and psychoactive substance dependence, psychotic disorder and generalized anxiety disorder occured significantly more frequently in the adolescent group. CONCLUSION: Our study draws the attention to the importance of the early recognition of ADHD, as well as the importance of the evaluation of comorbid externalizing and internalizing disorders in childhood and adolescence. Our result of the common co-occurrence of suicidal behavior and ADHD in both age groups is of great clinical relevance. More studies are needed to investigate the frequent comorbidity of ADHD and manic episode in childhood, because of the several overlapping symptoms of these disorders. PMID- 22781542 TI - [Wording and content of national anthems -- preliminary findings from a transcultural investigation of suicide]. AB - Suicide is still a major health concern, although suicide rates widely differ among different countries and cultures. Thus, besides biological and clinical studies, there is an increasing transcultural research activity on suicidal behaviour. We are presenting here some important transcultural aspects of suicidal behaviour and report some preliminary findings of our transcultural suicide research. Based on the previous data and on our investigations it is likely that the national character and the attitudes toward self-harm are reflecting in some major cultural, historical texts of a nation. PMID- 22781543 TI - [The psychiatric aspects of animal assisted therapy]. AB - Animal assisted therapy is a known preventive and interventive method which is held by the contribution of specially trained animals and professionals. One of its main indication fields is psychiatry. The purpose of this summary is to give an overview on the animal assisted therapy's background, possible uses and effectiveness with literature. It looks for the answer if this therapeutic method can be used for effectively easing the symptoms of specific psychiatric diseases and on which fields can it be used most effectively. Due to the data provided by literature it can be determined that the therapy supported by animals is able to give an effective help on the fields of various psychiatric supports, preventions, interventions and rehabilitations regardless of the age. It is mostly used in the case of depression, anxiety, addiction, schizophrenia and autism spectrum disorder. Aside from these it could also be used effectively in the rehabilitation of victims of sexual abuse especially in the case of children. It can also play a role in the re-socialization of inadapted adolescences and adults, even with farmtherapy. Due to experiences the therapies supported by animals are effective on the following fields: improving social and communication skills, easing anxiety, improving mood, helping independent living, improving emphatic skills. PMID- 22781544 TI - Characterization of interleukin-1 receptor-associated kinase 1 binding protein 1 gene in small abalone Haliotis diversicolor. AB - Interleukin receptor-associated kinase (IRAK)-1 binding protein 1 (IRAK1BP1) is a critical factor in preventing dangerous overproduction of proinflammatory cytokines by the innate immune system and in influencing the specificity of TLR responses. In this study, a first molluscan IRAK1BP1 gene, saIRAK1BP1, was cloned from the small abalone (Haliotis diversicolor). Its full-length cDNA sequence is 1047bp, with a 747bp open reading frame encoding a protein of 249 aa. The molecular mass of the deduced protein is approximately 28.1kDa with an estimated pI of 8.87, and shows highest identity (52%) to acorn worm Saccoglossus kowalevskii. Amino acid sequence analysis revealed that saIRAK1BP1 shares a conserved SIMPL domain. Quantitative real-time PCR was employed to investigate the tissue distribution of saIRAK1BP1 mRNA, and its expression in abalone under bacteria challenge and larvae at different developmental stages. The saIRAK1BP1 mRNA could be detected in all examined tissues, with the highest expression level in hemocytes, and was up-regulated in gills, kidneys and hemocytes after bacteria injection. Additionally, saIRAK1BP1 was constitutively expressed at all examined developmental stages. These results indicate that saIRAK1BP1 play an important role in the adult abalone immune system and might be essential in embryo and larval development in abalone. PMID- 22781545 TI - Survival benefit of traditional Chinese herbal medicine (a herbal formula for invigorating spleen) for patients with advanced gastric cancer. AB - BACKGROUND: Traditional Chinese herbal medicine (TCHM) is widely used for advanced gastric cancer (AGC) in China. In this study, the authors analyzed the prognostic factors of selected patients with AGC, and further studied the efficacy of TCHM (a herbal formula for invigorating spleen, formerly named Wei Chang' An) on AGC. METHODS: Patients with uncured AGC were prospectively enrolled. All patients were enrolled to either the TCHM group or non-TCHM group. TCHM was administered orally to the patients in the TCHM group for 3 months or more. Cox regression analysis was performed to determine survival trends adjusted for clinical and demographic factors. Kaplan-Meier curves were used to assess the differences in survival time. RESULTS: There were a total of 399 eligible patients with histologically confirmed adenocarcinoma of the stomach from 2001 to 2009. In the overall group, Cox regression analysis suggested that histological type (P = .016), radiotherapy (P = .000), cycle of chemotherapy (P = .000), and TCHM (P = .000) were independent prognostic factors. In a stratification analysis of stage for 213 patients who received 3 or more cycles of chemotherapy, there was a significant increase in median overall survival from 14.0 (non-TCHM group) to 20.0 (TCHM group) months (hazard ratio [HR] = 0.538, 95% confidence interval [CI] 0.385-0.750, P = .000). Among 186 patients who did not receive chemotherapy, but best supportive care, there was a significant increase in median overall survival from 7.0 (non-TCHM group) to 14.8 (TCHM group) months (HR = 0.443, 95% CI = 0.299-0.657, P = .000). CONCLUSIONS: TCHM has an important potential value for improving the prognosis of patients with AGC. PMID- 22781546 TI - Oxidative stress in stable cystic fibrosis patients: do we need higher antioxidant plasma levels? AB - Oxidative stress plays an important role in cystic fibrosis (CF). However, there is a lack of validated biomarkers of oxidative damage that correlate with the antioxidant needs of patients with CF. OBJECTIVE: To investigate oxidative stress in stable pediatric CF patients and evaluate if vitamin supplementation may be tailored to individual needs and oxidative status. RESULTS: Lipid-adducts 4 hydroxynonenal (HNE-L) and malonaldehyde (MDA-L) (chromolipids) were elevated in the majority of patients despite normal plasma vitamin E, A and C. HNE-L and MDA L increased with age, while plasma vitamins decreased. The most relevant correlation was identified between vitamin C and chromolipids. Patients with pancreatic insufficiency (PI) showed significantly higher plasma chromolipids despite no differences in plasma vitamins. CONCLUSIONS: The majority of patients showed elevated plasma chromolipids that increased with age. Antioxidant vitamin reference ranges provide incomplete information on the redox status. CF patients with PI showed excessive oxidative stress damage. PMID- 22781547 TI - A proposed consensus panel of organisms for determining evolutionary conservation of mt-tRNA point mutations. AB - Assigning pathogenicity to mt-tRNA variants requires multiple strands of evidence. Evolutionary conservation is often considered mandatory, but lack of a standard panel of organisms to assess conservation complicates comparison between reports and undermines the value of conservation-based evidence. We demonstrate that intra-species MTT sequence variation is sufficiently low for sequence data from a single organism to adequately represent a species. On this basis, we propose a standardised panel of organisms for conservation assessment and describe integration of this conservation panel into a pathogenicity scoring system designed to assess mt-tRNA variation associated with mitochondrial disease. PMID- 22781548 TI - Static hyperinflation is associated with decreased peak exercise performance in children with cystic fibrosis. AB - BACKGROUND: We evaluated the exercise capacity of children with cystic fibrosis to determine whether ventilatory limitation associated with static hyperinflation is related with decreased exercise capacity, thus predisposing these children to arterial hypoxemia during progressive exercise. METHODS: Thirty-seven children, ages 8-17 years, underwent spirometry, body plethysmography, and cardiopulmonary exercise testing after arterial catheter placement. According to the ratio of residual volume to total lung capacity (RV/TLC), the subjects were categorized as either with (RV/TLC > 30%) or without static hyperinflation (RV/TLC < 30%). RESULTS: Children with static hyperinflation showed lower values of maximum load per kilogram (% predicted) (P = .01), which was aggravated by ventilatory limitation (FEV(1) < 80% of predicted, peak oxygen consumption [% predicted] < 85%, and breathing reserve index > 0.7). Subjects with ventilatory limitation had significantly lower oxygen saturation (P = .04) and hypoxemia (P = .03) than did subjects without ventilatory limitation. CONCLUSIONS: In children with cystic fibrosis, static hyperinflation and ventilatory limitation are associated with decrease in exercise performance, oxygen saturation, and P(aO(2)) during maximum cardiopulmonary exercise testing. All children with cystic fibrosis who exhibit static hyperinflation and ventilatory limitation may require S(aO(2)) monitoring during progressive exercise. PMID- 22781550 TI - Fully automated sequential solid phase approach towards viral RNA-nucleopeptides. AB - The synthesis of two ribonucleoprotein fragments of unprecedented complexity is reported. These hybrid biomolecules are prepared combining the use of an automated solid phase peptide and oligonucleotide synthesizer on a single solid support. PMID- 22781549 TI - Progranulin regulates neuronal outgrowth independent of sortilin. AB - BACKGROUND: Progranulin (PGRN), a widely secreted growth factor, is involved in multiple biological functions, and mutations located within the PGRN gene (GRN) are a major cause of frontotemporal lobar degeneration with TDP-43-positive inclusions (FLTD-TDP). In light of recent reports suggesting PGRN functions as a protective neurotrophic factor and that sortilin (SORT1) is a neuronal receptor for PGRN, we used a Sort1-deficient (Sort1-/-) murine primary hippocampal neuron model to investigate whether PGRN's neurotrophic effects are dependent on SORT1. We sought to elucidate this relationship to determine what role SORT1, as a regulator of PGRN levels, plays in modulating PGRN's neurotrophic effects. RESULTS: As the first group to evaluate the effect of PGRN loss in Grn knockout primary neuronal cultures, we show neurite outgrowth and branching are significantly decreased in Grn-/- neurons compared to wild-type (WT) neurons. More importantly, we also demonstrate that PGRN overexpression can rescue this phenotype. However, the recovery in outgrowth is not observed following treatment with recombinant PGRN harboring missense mutations p.C139R, p.P248L or p.R432C, indicating that these mutations adversely affect the neurotrophic properties of PGRN. In addition, we also present evidence that cleavage of full-length PGRN into granulin peptides is required for increased neuronal outgrowth, suggesting that the neurotrophic functions of PGRN are contained within certain granulins. To further characterize the mechanism by which PGRN impacts neuronal morphology, we assessed the involvement of SORT1. We demonstrate that PGRN induced-outgrowth occurs in the absence of SORT1 in Sort1-/- cultures. CONCLUSION: We demonstrate that loss of PGRN impairs proper neurite outgrowth and branching, and that exogenous PGRN alleviates this impairment. Furthermore, we determined that exogenous PGRN induces outgrowth independent of SORT1, suggesting another receptor(s) is involved in PGRN induced neuronal outgrowth. PMID- 22781551 TI - An in vivo immunotherapy screen of costimulatory molecules identifies Fc-OX40L as a potent reagent for the treatment of established murine gliomas. AB - PURPOSE: We tested the combination of a tumor lysate vaccine with a panel of costimulatory molecules to identify an immunotherapeutic approach capable of curing established murine gliomas. EXPERIMENTAL DESIGN: Glioma-bearing mice were primed with a tumor lysate vaccine, followed by systemic administration of the following costimulatory ligands: OX40L, CD80, 4-1BBL, and GITRL, which were fused to the Fc portion of human immunoglobulin. Lymphocytes and mRNA were purified from the brain tumor site for immune monitoring studies. Numerous variations of the vaccine and Fc-OX40L regimen were tested alone or in combination with temozolomide. RESULTS: Lysate vaccinations combined with Fc-OX40L led to the best overall survival, yielding cure rates of 50% to 100% depending on the timing, regimen, and combination with temozolomide. Cured mice that were rechallenged with glioma cells rejected the challenge, showing immunologic memory. Lymphocytes isolated from the draining lymph nodes of vaccine/Fc-OX40L-treated mice had superior tumoricidal function relative to all other groups. Vaccine/Fc-OX40L treated mice exhibited a significant increase in proliferation of brain infiltrating CD4 and CD8 T cells, as indicated by Ki67 staining. Fc-OX40L had single-agent activity in transplanted and spontaneous glioma models, and the pattern of inflammatory gene expression in the tumor predicted the degree of therapeutic response. CONCLUSIONS: These data show that Fc-OX40L has unique and potent activity against experimental gliomas and warrants further testing. PMID- 22781552 TI - A phase I dose-escalation trial of trastuzumab and alvespimycin hydrochloride (KOS-1022; 17 DMAG) in the treatment of advanced solid tumors. AB - PURPOSE: We conducted a phase I dose-escalation study to define the maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics of alvespimycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, given in combination with trastuzumab. EXPERIMENTAL DESIGN: Patients were treated with trastuzumab followed by intravenous alvespimycin on a weekly schedule. Hsp90 client proteins were measured at baseline and serially in peripheral blood lymphocytes (PBL) during cycle 1. Patients with advanced solid tumors progressing on standard therapy were eligible. RESULTS: Twenty-eight patients (25, breast; 3, ovarian) were enrolled onto three dose cohorts: 60 (n = 9), 80 (n = 13), and 100 mg/m(2) (n = 6). Dose limiting toxicities (DLT) were: grade III left ventricular systolic dysfunction presenting as congestive heart failure in 1 patient (100 mg/m(2)), and reversible grade III keratitis in two patients (80 mg/m(2)). Drug-related grade III toxicity included one episode each of fatigue, diarrhea, myalgia, and back pain. Common mild to moderate toxicities included diarrhea, fatigue, myalgia, arthralgia, nausea, blurry vision, headache, back pain, and dry eyes. There was one partial response and seven cases of stable disease (range, 4-10 months), all in HER2+ MBC. In addition, an ovarian cancer patient had complete resolution of ascites and pleural effusion that lasted 24.8 months. There was no change in PK upon weekly dosing. Hsp70 effect continued to increase across four weeks and was most pronounced at 80 and 100 mg/m(2). CONCLUSION: The combination of alvespimycin and trastuzumab is safe and tolerable at MTD. Antitumor activity was seen in patients with refractory HER2+ MBC and ovarian cancer. The recommended dose of alvespimycin for further study in this combination is 80 mg/m(2) weekly. PMID- 22781553 TI - AT13148 is a novel, oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity. AB - PURPOSE: Deregulated phosphatidylinositol 3-kinase pathway signaling through AGC kinases including AKT, p70S6 kinase, PKA, SGK and Rho kinase is a key driver of multiple cancers. The simultaneous inhibition of multiple AGC kinases may increase antitumor activity and minimize clinical resistance compared with a single pathway component. EXPERIMENTAL DESIGN: We investigated the detailed pharmacology and antitumor activity of the novel clinical drug candidate AT13148, an oral ATP-competitive multi-AGC kinase inhibitor. Gene expression microarray studies were undertaken to characterize the molecular mechanisms of action of AT13148. RESULTS: AT13148 caused substantial blockade of AKT, p70S6K, PKA, ROCK, and SGK substrate phosphorylation and induced apoptosis in a concentration and time-dependent manner in cancer cells with clinically relevant genetic defects in vitro and in vivo. Antitumor efficacy in HER2-positive, PIK3CA-mutant BT474 breast, PTEN-deficient PC3 human prostate cancer, and PTEN-deficient MES-SA uterine tumor xenografts was shown. We show for the first time that induction of AKT phosphorylation at serine 473 by AT13148, as reported for other ATP competitive inhibitors of AKT, is not a therapeutically relevant reactivation step. Gene expression studies showed that AT13148 has a predominant effect on apoptosis genes, whereas the selective AKT inhibitor CCT128930 modulates cell cycle genes. Induction of upstream regulators including IRS2 and PIK3IP1 as a result of compensatory feedback loops was observed. CONCLUSIONS: The clinical candidate AT13148 is a novel oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity, which shows a distinct mechanism of action from other AKT inhibitors. AT13148 will now be assessed in a first-in human phase I trial. PMID- 22781554 TI - The strength of species interactions modifies population responses to environmental variation in competitive communities. AB - The life-history parameters of most living organisms are modified by fluctuations in environmental conditions. The impact of environmental autocorrelation on population persistence is well understood in single species systems. However, in multi-species communities the impact of stochasticity is complicated by the possibility of different species having differing intrinsic responses to the environment (environmental correlation). Previous work has shown that whether increasing between-species environmental correlation stabilises population fluctuations or not, depends on an interaction between density-dependence and environmental autocorrelation. Here we derive analytical conditions for how this interaction in turn depends on the strength of interspecific competition. Under relatively weak between-species interactions, increasing environmental autocorrelation always dampens population fluctuations, while increasing autocorrelation destabilises strongly interacting populations. In contrast, under intermediate interaction strengths, increasing autocorrelation destabilises (stabilises) population dynamics when populations respond independently (similarly) to environmental fluctuations. These results apply to a wide range of competitive communities and also have some relevance to consumer-resource systems. The results presented here help us better understand population responses to environmental fluctuations under different conditions. PMID- 22781555 TI - Evolutionary and convergence stability for continuous phenotypes in finite populations derived from two-allele models. AB - The evolution of a quantitative phenotype is often envisioned as a trait substitution sequence where mutant alleles repeatedly replace resident ones. In infinite populations, the invasion fitness of a mutant in this two-allele representation of the evolutionary process is used to characterize features about long-term phenotypic evolution, such as singular points, convergence stability (established from first-order effects of selection), branching points, and evolutionary stability (established from second-order effects of selection). Here, we try to characterize long-term phenotypic evolution in finite populations from this two-allele representation of the evolutionary process. We construct a stochastic model describing evolutionary dynamics at non-rare mutant allele frequency. We then derive stability conditions based on stationary average mutant frequencies in the presence of vanishing mutation rates. We find that the second order stability condition obtained from second-order effects of selection is identical to convergence stability. Thus, in two-allele systems in finite populations, convergence stability is enough to characterize long-term evolution under the trait substitution sequence assumption. We perform individual-based simulations to confirm our analytic results. PMID- 22781556 TI - Views of translational research from a somewhat translational scientist. AB - This review arose from a talk entitled "Identifying Targets" and given by the author at EB2011 at the invitation of the American Federation for Medical Research (AFMR). The presentation was part of the American Federation for Medical Research workshop entitled "Keys for Translation: Science and Strategy" and focused on identifying clinically relevant targets as a result of observations made during basic scientific studies. The review emphasizes that targets do not have to be the aim that drives basic discovery, but communication between the basic scientist and clinical investigators may aid recognition of such targets and their translation to clinical applications. Using one line of investigator initiated research from his own laboratory as an example, the author emphasizes that basic discovery must be hypothesis driven and allowed to follow its logical sequence. Finding treatments, while always an aim of biomedical research, may arise as a result of basic studies that were not originally aimed at a target of translational research. PMID- 22781557 TI - Fabrication of crystal alpha-Si3N4/Si-SiOx core-shell/Au-SiOx peapod-like axial double heterostructures for optoelectronic applications. AB - Novel crystal alpha-Si(3)N(4)/Si-SiO(x) core-shell/Au-SiO(x) peapod-like axial double heterostructural nanowires were obtained by directly annealing a Au covered SiO(2) thin film on a Si substrate. Our extensive electron microscopic investigation revealed that the alpha-Si(3)N(4) sections with a mathematical left angle bracket 101 mathematical right angle bracket growth direction were grown first, followed by growth of the Si-SiO(x) core-shell sections and finally growth of the Au-SiO(x) peapod-like sections. Through a series of systematically comparative experiments, a temperature-dependent multi-step vapor-liquid-solid growth mechanism is proposed. Room temperature photoluminescence measurement of individual nanowires reveals two emission peaks (410 and 515 nm), indicating their potential applications in light sources, laser or light emitting display devices. PMID- 22781558 TI - Noninvasive ventilation coupled with nebulization during asthma crises: a randomized controlled trial. AB - BACKGROUND: Despite the clinical improvements attributed to noninvasive ventilation (NIV) during asthma crises, and the well established effects of nebulization, there are few studies on the effects of these interventions together. We hypothesized that nebulization coupled to NIV should raise radio aerosol pulmonary deposition in asthmatics. The aims of this study were to assess the effects of coupling beta-agonist nebulization and NIV during asthma exacerbations on radio-aerosol pulmonary deposition, using scintigraphy and cardiopulmonary parameters, to correlate pulmonary function with radio-aerosol deposition index, radio-aerosol penetration index, and pulmonary clearance. METHODS: In this controlled trial, 21 adults with moderate to severe asthma attack were randomized to a control group (n = 11) or experimental group (NIV + nebulizer group, n = 10). All subjects inhaled bronchodilators for 9 minutes, and after particles were counted with a gamma camera to analyze regions of interest and pulmonary clearance at 0, 15, 30, 45, and 60 min. RESULTS: Breathing frequency (P = < .001) and minute ventilation (P = .01) were reduced, and tidal volume was increased (P = .01) in the NIV + nebulizer group, compared with the control group. The NIV + nebulizer group had improvement from baseline values, compared to the control group in the following parameters: FEV(1) 46.7 +/- 0.5% of predicted vs 29.8 +/- 8.9% of predicted, P = .02), FVC (41.2 +/- 1.5% of predicted vs 23.2 +/- 7.1% of predicted, P = .02), peak expiratory flow (67.3 +/- 38.3% of predicted vs 26.9 +/- 12.1% of predicted, P = .01), and inspiratory capacity (54.9 +/- 28.8% of predicted vs 31.2 +/- 9.1% of predicted, P = .01). No differences were observed between groups regarding radio-aerosol deposition index or pulmonary clearance. Negative correlations were found between FEV1, forced expiratory flow during the middle half of the FVC maneuver (FEF(25-75%)), inspiratory capacity, and radio-aerosol penetration index. CONCLUSIONS: Coupling nebulization and NIV during asthma exacerbation did not improve radio-aerosol pulmonary deposition, but we observed clinical improvement of pulmonary function in these subjects. (ClinicalTrials.gov registration NCT01012050). PMID- 22781559 TI - Neighbourhood deprivation and outlet density for tobacco, alcohol and fast food: first hints of obesogenic and addictive environments in Germany. AB - OBJECTIVE: The current discussion regarding 'place effects on health' is increasingly focusing on the characteristics of a specific physical environment. Our study investigated whether socially deprived residential areas are more likely than affluent neighbourhoods to provide access to addictive substances and fast food. DESIGN: In this ecological study the total number of tobacco, alcohol and fastfood outlets was recorded and visualized using a geographic information system. Area affluence was measured through the percentage of parents with children of kindergarten or school age with joint annual taxable income ,h12 272. SETTING: Eighteen social areas in Cologne, Germany. SUBJECTS: All social areas in four districts in Cologne, Germany, with a total of 92 000 inhabitants, were analysed. RESULTS: In the investigation area, 339 tobacco, 353 alcohol and sixty seven fastfood outlets were identified. As area affluence declined the availability of the following potentially health damaging sources increased: cigarettes (Kendall's tau50?433; P50?012), alcohol (Kendall's tau50?341, P50?049) and fast food (Kendall's tau50?473; P50?009). CONCLUSIONS: The availability of addictive substances and fast food can be seen to have a contextual influence on an individual's lifestyle and can, in the form of physical exposure to obesogenic and addictive environments, contribute to a culmination of health risks. PMID- 22781561 TI - [An overview of Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) (revised 2011)]. PMID- 22781560 TI - Quantification of the internalization patterns of superparamagnetic iron oxide nanoparticles with opposite charge. AB - Time-resolved quantitative colocalization analysis is a method based on confocal fluorescence microscopy allowing for a sophisticated characterization of nanomaterials with respect to their intracellular trafficking. This technique was applied to relate the internalization patterns of nanoparticles i.e. superparamagnetic iron oxide nanoparticles with distinct physicochemical characteristics with their uptake mechanism, rate and intracellular fate.The physicochemical characterization of the nanoparticles showed particles of approximately the same size and shape as well as similar magnetic properties, only differing in charge due to different surface coatings. Incubation of the cells with both nanoparticles resulted in strong differences in the internalization rate and in the intracellular localization depending on the charge. Quantitative and qualitative analysis of nanoparticles-organelle colocalization experiments revealed that positively charged particles were found to enter the cells faster using different endocytotic pathways than their negative counterparts. Nevertheless, both nanoparticles species were finally enriched inside lysosomal structures and their efficiency in agarose phantom relaxometry experiments was very similar.This quantitative analysis demonstrates that charge is a key factor influencing the nanoparticle-cell interactions, specially their intracellular accumulation. Despite differences in their physicochemical properties and intracellular distribution, the efficiencies of both nanoparticles as MRI agents were not significantly different. PMID- 22781562 TI - [Interpretation of Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) (revised 2011)]. PMID- 22781563 TI - [Bacterial infection and immunity in chronic obstructive pulmonary disease pathogenesis and processes]. PMID- 22781564 TI - [Incidence of comorbidities in hospitalized chronic obstructive pulmonary disease patients and correlated risk factors]. AB - OBJECTIVE: To explore the incidence of comorbidities in hospitalized chronic obstructive pulmonary disease (COPD) patients and influencing factors. METHODS: A retrospective review of medical records was performed for 495 hospitalized COPD patients in Peking University Third Hospital from January 2003 to December 2008. Their comorbidities were identified and ranked in prevalence. The risk factors of comorbidities were analyzed by multivariable Logistic regression. RESULTS: The most frequent comorbidities were: hypertension (60.0%), ischemic heart disease (16.0%), malignant tumor (10.9%), diabetes mellitus (10.5%), chronic heart failure (9.9%) and dyslipidemia (9.9%). The percentage of patients with ischemic heart disease in people with FEV(1)% Pred < 30%, 30% <= FEV(1)%Pred < 50%, 50% <= FEV(1)%Pred < 80% and FEV(1)%Pred >= 80% were 9.2%, 12.7%, 21.3% and 16.5% respectively (P = 0.052). The percentage of patients with dyslipidemia in people with FEV(1)%Pred < 30%, 30% <= FEV(1)%Pred < 50%, 50% <= FEV(1)%Pred < 80%, FEV(1)%Pred >= 80% were 5.3%, 5.7%, 10.9% and 20.3% respectively (P = 0.002). The percentage of patients with ischemic heart disease in people with body mass index (BMI) < 18.5, 18.5 - 23.9, 24.0 - 27.9, >= 28.0 kg/m(2) were 13.6%, 14.2%, 14.6% and 28.3% respectively (P = 0.051). The percentage of patients with dyslipidemia in people with BMI < 18.5, 18.5 - 23.9, 24.0 - 27.9, >= 28.0 kg/m(2) were 5.5%, 5.7%, 14.6% and 25.0% respectively (P = 0.000). The levels of C-reactive protein (CRP) were higher than the 75(th) percentile (OR = 2.371, P = 0.014), and complications with metabolic syndrome (OR = 2.694, P = 0.003) were independent risk factors of ischemic heart disease in COPD patients. CONCLUSIONS: The incidence of comorbidities varies in different COPD populations. Higher levels of CRP and complications with metabolic syndrome are independent risk factors of ischemic heart disease in COPD patients. PMID- 22781565 TI - [Preliminary proteomic analysis of peripheral skeletal muscle atrophy in chronic obstructive pulmonary disease]. AB - OBJECTIVE: To conduct a preliminary proteomic study of chronic obstructive pulmonary disease (COPD) with peripheral skeletal muscle atrophy. METHODS: A total of 16 COPD patients and 8 aged-matched persons because of bone fractures were recruited in First Hospital Affiliated to Kunming Medical College from February to July in 2010. According to body mass index, fat free mass index, quadriceps femoris perimeter and quadriceps femoris active contraction, they were divided into those with muscle atrophy (group A, n = 8) and those without (group B, n = 8). There were 6 males and 2 females with an average age of (70 +/- 8) years in the group A and 5 males and 3 females with an average age of (74 +/- 8) years in the group B. And the control group had 6 males and 2 females with an average age of (72 +/- 6) years. All samples of total quadriceps protein were separated by two-dimensional gel electrophoresis. The abnormal protein points on electrophoresis were compared by PDQuest image software. And the differential protein expression was detected. Then the corresponding peptide quality fingerprint spectrum was analyzed by mass spectrometer. Finally the differential protein points were partially detected by a search of database. RESULTS: The two dimensional gel electrophoresis yielded an excellent profile of resolution and repeatability. And 12 proteins likely to cause skeletal muscle atrophy in COPD were identified. Among them, 8 proteins belonged to structural proteins (actin alpha cardiac muscle isoform CRA_c, myosin regulatory light chain 2, ventricular/cardiac muscle isoform, myoglobin isoform myosin heavy polypeptide 7 cardiac muscle beta isoform CRA_c, actin, alpha skeletal muscle, actin alpha cardiac muscle isoform CRA_b, hemoglobin alpha 1 globin chain & myosin light chain 6B) and 4 proteins were of functional proteins (chain A, crystal structure of human enolase; troponin T, slow skeletal muscle isoform alpha, carbonate anhydrase, troponin T & slow skeletal muscle isoform b). CONCLUSIONS: COPD patients are often accompanied with obvious peripheral skeletal muscle atrophy. It may be caused by quantitative or qualitative changes of peripheral skeletal structural and functional proteins. PMID- 22781566 TI - [Effects of shadow boxing training on exercise endurance and quality of life of patients with chronic obstructive pulmonary disease]. AB - OBJECTIVE: To evaluate the effects of shadow boxing training on the exercise endurance and quality of life of Chinese patients with COPD (chronic obstructive pulmonary disease). METHODS: From May 2010 to March 2011, a total of 70 COPD patients in stable phases were recruited from Liwan, Yuexiu and Haizhu districts of Guangzhou. There were 35 patients in the shadow boxing exercise group and 35 patients in the control group. And they were matched by gender and age. The patients in the shadow boxing group exercised for 3 months while those in the control group received the conventional out-hospital management only. Their demographic, medical history, smoking status, medicinal use, spirometric data, clinical COPD questionnaire (CCQ) scores, 6-minute walking distance and Borg scores were collected before and after trial. RESULTS: A total of 63 COPD patients (33 in shadow boxing group vs. 30 in control group) completed the study. There was an average dropout rate of 5.7% (2/35) in shadow boxing group and 14.3% (5/35) in control group. No differences existed between two groups in age (67 +/- 8 vs 69 +/- 9 yr), male proportion (84.8% vs 86.7%), body mass index (22.8 +/- 2.6 vs 22.7 +/- 3.0), usage proportion of medicine (42.4% vs 33.3%), duration of disease (4.0 +/- 7.5 vs 5.5 +/- 7.3), percentage of smokers (78.8% vs 80.0%), 6 minute walking distance (447 +/- 94 vs 414 +/- 100), CCQ total score (15.0 +/- 9.4 vs 14.1 +/- 8.8), CCQ symptom score (9.2 +/- 5.6 vs 8.3 +/- 5.0) and activity score (5.8 +/- 4.5 vs 5.8 +/- 4.4) at baseline (all P > 0.05). At the end of study, the 6-minute walking distance of patients had statistical differences between two groups (P < 0.01). The shadow boxing group increased by (51 +/- 55) m while the control dropped by (19 +/- 58) m. The total score, symptom score and activity score of clinical COPD questionnaire had statistical differences between two groups. They decreased significantly in the shadow boxing group as compared with the baseline data while there was no significant change in the control group. No statistical differences existed between two groups in the changes of forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)), FEV(1)% pred, Borg score and dyspnea scales. CONCLUSION: Capable of improving the exercise endurance and life quality of COPD patients, shadow boxing exercise may become one of effective rehabilitation programs for COPD patients in stable phases in communities. PMID- 22781567 TI - [Expression of phosphorylated STAT5 in bone marrow hematopoietic stem cells of patients with paroxysmal nocturnal hemoglobinuria before and after in vitro G-CSF or SCF stimulation]. AB - OBJECTIVE: To study the expressions of phosphorylated STAT5 (P-STAT5) in CD34(+)CD59(-) and CD34(+)CD59(+) bone marrow cells of the patients with paroxysmal nocturnal hemoglobinuria (PNH) before and after in vitro G-CSF or SCF stimulation, then evaluate the functions of G-CSF and SCF receptors in PNH clone cells. METHODS: Bone marrow mononuclear cells (BMMNC) of 26 PNH patients and 14 normal controls were stimulated in vitro with G-CSF (100 ng/ml) or SCF (100 ng/ml) for 10 min. Before and after these stimulations, the mean fluorescence intensity (MFI) of P-STAT5 in CD34(+)CD59(+) BMMNC and CD34(+)CD59(-) BMMNC were measured by flow cytometry. RESULTS: (1) The P-STAT5 MFI was (24 +/- 18) in unstimulated CD34(+)CD59(-) cells. And it was significantly lower than that in unstimulated CD34(+)CD59(+) cells of PNH patients (64 +/- 49) and normal controls (61 +/- 33) (both P < 0.01). No statistic difference existed between the latter two. (2) The P-STAT5 MFI was (36 +/- 35) in G-CSF stimulated CD34(+)CD59(-) cells of PNH patients. And it was significantly lower than that in G-CSF stimulated CD34(+)CD59(+) cells of PNH patients (124 +/- 84) and normal controls (116 +/- 59) (both P < 0.01). There was no statistic difference between the latter two. (3) The P-STAT5 MFI was (34 +/- 27) in SCF stimulated CD34(+)CD59(-) cells of PNH patients. And it was significantly lower than that in SCF stimulated CD34(+)CD59(+) cells of PNH patients (124 +/- 97) and normal controls (128 +/- 62) (both P < 0.01). And no statistic difference existed between the latter two. (4) The increased P-STAT5 MFI in G-CSF stimulated CD34(+)CD59(-) cells of PNH patients was significantly lower than that in G-CSF stimulated CD34(+)CD59(+) cells of PNH patients and normal controls (both P < 0.01). No statistic difference existed between the latter two. The increase of P-STAT5 MFI in SCF stimulated CD34(+)CD59(-) cells of PNH patients was significantly lower than that in SCF stimulated CD34(+)CD59(+) cells of PNH patients and normal controls (both P < 0.01). No statistic difference existed between the latter two. CONCLUSION: There is a lower expression of P-STAT5 expressed in G-CSF or SCF stimulated PNH clone cells compared to that in normal clone cells. PMID- 22781568 TI - [Risk factors for acquired multidrug-resistant Acinetobacter baumannii colonization in respiratory intensive care unit]. AB - OBJECTIVE: To determine the risk factors for respiratory intensive care unit (RICU)-acquired colonization of multidrug-resistant Acinetobacter baumannii (MDR AB). METHODS: From January 2010 to June 2011, active screening was performed to define patients with RICU-acquired colonization of MDR-AB. And environment surveillance was carried out and patient data were collected. Logistic regression was applied to identify the risk factors of RICU-acquired colonization of MDR-AB. RESULTS: Active screening for MDR-AB was performed for 110 patients in RICU and 50 patients turned out to be positive. After eliminating 3 input positive patients, the RICU-acquired colonization rate of MDR-AB was 43.9% (47/107). The environmental contaminated rate of MDR-AB was 66.0% (31/47) for 47 positive patients and 33.9% (19/56) for 56 negative ones (chi(2) = 10.494, P < 0.01). Five risk factors were associated with the colonization of MDR-AB through univariate analysis: consciousness disturbance, use of carbapenems, nasal feeding tube, endotracheal intubation and mechanical ventilation (all P < 0.05). The Logistic regression equation contained 3 risk factors of conscious disturbance, use of carbapenems and mechanical ventilation (OR = 3.412, 3.211, 3.002; 95% CI: 1.165 - 9.992, 1.117 - 9.233, 1.101 - 8.182). CONCLUSION: Three risk factors are independently associated with the RICU-acquired colonization of MDR-AB: consciousness disturbance, use of carbapenems and mechanical ventilation. PMID- 22781569 TI - [Expression analysis of NOTCH1/HES1/PTEN signaling pathway in invasive bladder transitional cell carcinoma]. AB - OBJECTIVE: To explore the role of NOTCH1/HES1/PTEN signaling pathway in invasive TCCB (bladder transitional cell carcinoma). METHODS: The expressions of NOTCH1, HES1 and PTEN were detected in 36 cases of invasive TCCB tissues and 10 cases of normal bladder samples by real-time q-polymerase chain reaction (q-PCR) and Western blot. Then NOTCH1-ORF plasmid and its blank vector pCMV6-Entry were transfected into T24 cell respectively. And the expressions of three above mentioned target genes were measured by real-time q-PCR and Western blot. Furthermore, cell proliferation, cell apoptosis and cell cycle were analyzed respectively by MTS assay and flow cytometry. RESULTS: Compared with normal bladder samples, the higher levels of both mRNA and protein of NOTCH1 and HES1 were detected in invasive TCCB tissues while there was a lower expression of PTEN (P < 0.05). The mRNA expression levels of NOTCH1 and HES1 were 4.22 and 3.75 folds respectively higher than those of normal tissues. In NOTCH1-overexpressed T24 cell, the expression of HES1 was 5.43 folds higher than that of the blank vector control group while the expression of PTEN declined to 41.76% (P < 0.01). MTS assay showed that the NOTCH1-ORF transfection obviously promoted cell proliferation in T24 cell (P < 0.01). CONCLUSION: NOTCH1 gene may function as an oncogene by regulating HES1/PTEN in invasive TCCB and its aberrant activation promotes cell proliferation. PMID- 22781570 TI - [Safety and efficacy of pitavastatin in patients with hypercholesterolemia: a multicenter study]. AB - OBJECTIVE: To evaluate the safety and efficacy of pitavastatin in patients with hypercholesterolemia in China under conditions of extensive usage. METHODS: This was a 12-week, multicenter, open-label, without parallel-group comparison, phase IV clinical trial. RESULTS: There were 427 subjects in the safety set. The adverse events mainly included vomiting, myalgia and the elevations of aspartate transaminase (AST), alanine transaminase (ALT) and creatine kinase (CK), etc. The incidence of drug-related adverse events was 4.22%. There were no significant differences between pre-exposure and post-exposure average levels of renal function indicators and blood routine examination item (all P > 0.05). None of them had a high AST/ALT value, i.e. > 3 times upper limits of normal (ULN), or had a high CK value, i.e. > 10 times ULN. There were 397 subjects in the per protocol set. At week 12 post-treatment, the blood levels of total cholesterol and low density lipoprotein cholesterol (LDL-C) in subjects without previous treatment decreased 24.6% and 31.0% respectively, that of high density lipoprotein cholesterol (HDL-C) in subjects with HDL-C < 1.04 mmol/L increased 60.1% while that of triglyceride (TG) in subjects with TG > 1.70 mmol/L decreased 22.5% (P < 0.05). And 207 (92.3%) subjects were at a low risk, 46 (76.1%) subjects at an intermediate risk, 134 (47.8%) subjects at a high risk and 10 (40.0%) of subjects at a very high risk had achieved a LDL-C target value; the LDL-C goal achievement rate after switching from previous medication to pitavastatin was significant higher than that of pre-switching. CONCLUSION: Pitavastatin demonstrates positive safety and efficacy. It may be used for the treatment of patients with hypercholesterolemia in China. PMID- 22781571 TI - [Comparison of sternotomy off-pump coronary artery bypass and minimally invasive technique for isolated single vessel grafting]. AB - OBJECTIVE: To compare the outcomes of minimally invasive coronary artery bypass grafting operation performed via a small thoracotomy versus da Vinci S system (Endo-A-CAB) with sternotomy off-pump coronary artery bypass grafting (OPCAB) for single vessel lesion. METHODS: From April 2000 to August 2011, a total of 194 patients with single coronary artery stenosis accepted CABG on beating heart were divided into 2 groups by different surgical approaches. Group A (n = 99) received sternotomy OPCAB while Group B (n = 95) underwent Endo-A-CAB. All patients had a history of unstable angina and coronary arteriography showed severe stenosis in left anterior descending artery (LAD). The procedure performed in Group B included robotic internal mammary artery (IMA) harvesting and single manual anastomosis to LAD and/or diagonal branch through small incision thoracotomy. IMA flow was evaluated by the Doppler flow meter after the completion of anastomosis. Grafting patency was evaluated postoperatively by computed tomography angiography (CTA) or angiography. RESULTS: The ventilation time and postoperative drainage volume in Group B were less than those in Group A ((5.1 +/- 2.1) vs (10.1 +/- 5.8) h, P = 0.03; (411 +/- 295) vs (605 +/- 244) ml, P = 0.000). No significant difference existed in blood flow, mortality and postoperative complication morbidity between two groups. All symptoms of angina disappeared. CONCLUSION: As a new advanced modality of revascularization, in comparison with OPCAB, Endo-A CAB procedure is a less invasive and safer method of coronary artery bypass grafting for single vessel lesion. PMID- 22781572 TI - [Radiofrequency catheter ablation for ventricular premature beats of left coronary cusp under the guidance of 3-dimensional mapping system]. AB - OBJECTIVE: To explore the efficacy and safety of radiofrequency catheter ablation (RCA) for ventricular premature beats originating from left coronary sinus under the guidance of 3-dimensional mapping system (CARTO). METHODS: A total of 15 patients with premature ventricular contractions (PVCs) originating from left coronary sinus underwent CARTO-guided RCA. Anatomical structures were constructed and three-dimension (3D) electrical activation sequence was plotted for left ventricle and aortic sinus. The distance of earliest activation point of PVCs and origin of left coronary artery were surveyed after left coronary arteriography. RESULTS: The electrocardiogram (ECG) results showed that R-wave was upward in leads II, III and avF, QRS waves in lead I was mainly of rS, rs and rsr types, QS type in lead avL, RS, Rs and rS type in lead V(1), RS type in lead V(3) and absence of S wave in lead V(5)/V(6). Intraoperative mapping detected the earliest activation point on the posterior-inferior origin of left coronary artery (LMCA) ostium (n = 7), on the anterio-inferior of LMCA ostium (n = 3) and on the inferior of LMCA ostium (n = 5). The earliest activation point (local activation time) was shorter 86 - 120 ms than surface electrocardiogram QRS wave, discharge melting on the earliest activation point and nearby succeeded. PVCs disappeared, PVCs failed to be induced under similar preoperative conditions (aleudrin intravenous) and no complication occurred intraoperatively and postoperatively. CONCLUSION: The CARTO-guided RCA is a safe and effective in the treatment of PVCs originating from left coronary sinus. PMID- 22781573 TI - [The study of the risk factors of fungal infection after liver transplantation]. AB - OBJECTIVE: To explore the risk factors of fungal infection so as to provide rationales for the prevention of fungal infection after liver transplantation. METHODS: The clinical data of 94 cases of fungal infections after liver transplantation from January 1, 2003 to November 30, 2010 at our hospital were collected as the infective group. A total of 603 liver transplant patients without fungal infections during the same period were selected as the control group. chi(2) test and t test were utilized for the analysis of possible risk factors for fungal infection. RESULTS: Fungal infection rate was 13.5% (94/697) after liver transplantation and mortality rate of fungal infection 86.2% (81/94). Candida albicans was the majority infective fungi. And the main site of infection was the lungs. The postoperative acute physiology and chronic health evaluation III (APACHE III) score of the infective group was significantly higher than that of the control group (26.0 +/- 5.4 vs 21.5 +/- 4.7, P < 0.01). The number of patients with primary liver cancer was lower than that of the control group (26.6% vs 45.8%, P < 0.01). The number of decompensated HBV cirrhosis and diabetics in the infective group was higher than that of the control group at pre operation (23.4% vs 11.6%, 9.6% vs 2.8%, both P < 0.01). The number of patients with postoperative mechanical ventilation over 10 days, postoperative antibiotics over 14 days, postoperative cardiopulmonary dysfunction and liver function recovery time over 7 days, parenteral nutrition over 12 days and hyperglycemia over 7 days in the infective group were significantly higher than that in the control group (all P < 0.01). CONCLUSION: Preoperative primary disease, postoperative disease severity, postoperative organ dysfunction, long-term mechanical ventilation, antibiotics and hyperglycemia, etc. may be the important risk factors of fungal infection after liver transplantation. PMID- 22781574 TI - [Diagnosis and treatment of seminal vesicle cyst]. AB - OBJECTIVE: To deepen the understanding of patients with seminal vesicle cyst to facilitate its correct diagnosis and treatment. METHODS: Five patients with seminal vesicle cysts were treated during January 1996 to May 2010. Their symptoms, diagnostic results, treatments and outcomes were analyzed retrospectively. Their mean age at diagnosis was 35 years old (range: 20 - 45). The symptoms included hematospermia (n = 3), urinary frequency (n = 3), perineal malaise (n = 4), infertility (n = 3), post-ejaculation pain (n = 3), scrotal pain (n = 3) and dysuria (n = 1). Cyst was palpable on digital rectal examination in 4 patients. All underwent intravenous urography and cystoscopy. Others received the examinations of ultrasonography, computed tomography (CT) scanning, magnetic resonance imaging (MRI) and vaso-vesiculography. The size range of masses was from 3.8 cm * 3.0 cm * 2.6 cm-9.6 cm * 5.2 cm * 5.0 cm. Final open operations consisted of vesiculectomy (n = 2) and laparoscopic excision of seminal vesical cyst (n = 3). RESULTS: The post-operative course was uneventful except in 1 patient with damaged ureters. All patients stayed symptom-free after open surgery. CONCLUSION: Seminal vesicle cysts are rare but should be considered in males with hematospermia and otherwise inexplicable bladder irritation symptoms, perineal discomforts or other genitourinary complaints of unknown etiology. The diagnostic modalities consist of digital rectal examination, transrectal and abdominal ultrasonography, CT scan or MRI. Laparoscopic excision offers excellent outcomes. PMID- 22781575 TI - [Role and mechanism of motilin in colonic motility disorder]. AB - OBJECTIVE: To explore the role and mechanism of motilin in colonic motility disorder. METHODS: A total of 20 male Wistar rats (180 - 200 g) were randomly divided into 2 groups: water avoidance stress (WAS, n = 10) and sham water avoidance stress (SWAS, n = 10). Rats were exposed to 1 h WAS or SWAS daily for 10 consecutive days. Motilin in plasma was measured by enzyme-linked immunosorbent assay (ELISA). Proximal colon circular smooth muscle cells (PCSM) were isolated by enzymatic digestion and L-type calcium currents (ICa(L)) recorded by patch-clamp techniques. RESULTS: The fecal pellets during 1 h WAS significantly increased (5.4 +/- 1.0 vs 2.4 +/- 0.7, P < 0.01, n = 10). The motilin in plasma had significant difference between WAS rats and SWAS rats ((135 +/- 35) vs (89 +/- 24) pg/ml, P < 0.01, n = 10). The ICa(L) of two rats had no significant difference. But 6 * 10(-5) mmol/L motilin increased ICa(L) more in WAS than in SWAS rats at 0 mV ((1.6 +/- 0.4) vs (1.0 +/- 0.3) pA/pF, P < 0.05, n = 10). CONCLUSION: WAS leads to elevated motilin levels in plasma and active L type Ca(2+) channels in colon. And it contributes to colonic motility disorder. PMID- 22781576 TI - [Protective effects of N-acetylcysteine on cochlear damage occur in guinea pigs exposed to irradiation]. AB - OBJECTIVE: To explore the protective effects of N-acetylcysteine (NAC) on cochlear damage occurring in irradiated guinea pigs. METHODS: Seventy-two guinea pigs were randomly divided into 4 groups (n = 18 each). Control group received neither NAC nor irradiation, irradiation group received total cranium irradiation of 70 Gy, irradiation & saline group cranium irradiation of 70 Gy and saline solution through a round window and NAC group cranium irradiation of 70 Gy and NAC through a round window. The right ear received radiation. The animals were sacrificed at Day 14 post-irradiation. The specimens were dehydrated, embeded in paraffin and serially cut into 5-um slices. Sections were stained with immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL). The cochlear basal membranes were observed for malondialdehyde (MDA) and superoxide dismutase (SOD) with scanning electron microscope. RESULTS: The cilium of hair cells had no clear loss and apoptotic number of spiral ganglion cells decreased in NAC group. The average optical density value of Caspase 3 in spiral ganglion in NAC group significantly decreased versus the irradiation group (0.08 +/- 0.02 vs 0.10 +/- 0.01, P < 0.01). The level of MDA of NAC group also decreased versus the irradiation group (0.33 +/- 0.05 vs 0.84 +/- 0.13, P < 0.05). The level of SOD in the NAC group increased versus the irradiation group (10.7 +/- 3.0 vs 8.7 +/- 1.3, P < 0.05). The ratio of apoptotic cell in SGC in the NAC group at Day 14 (7.8% +/- 1.8%) decreased versus the irradiation group (32.0% +/- 8.7%) at Day 14. CONCLUSION: MDA and SOD may be involved in the pathogenesis of cochlear cell damage. And NAC protects the irradiated cochlear cell. PMID- 22781577 TI - [Protective effects and possible mechanism of lipoxin A(4) analogue in rats with acute pancreatitis]. AB - OBJECTIVE: To explore the protective effects and possible mechanism of lipoxin A(4)-methyl ester (LXA(4)-ME) in rats with acute pancreatitis (AP). METHODS: A total of 120 male SD rats were randomly divided into 3 groups: Sham operation (n = 40), AP (n = 40) and LXA(4)-ME (n = 40). Sham operation group received normal saline after sham operation. AP was induced by a retrograde infusion of 5% sodium taurocholate into pancreatobiliary duct. AP group received normal saline after modeling. In the LXA(4)-ME group, LXA(4)-ME was administered (87.5 ug/kg) intravenously after the onset of AP. The rats were sacrificed at 12 h and 24 h post-induction. Their serum levels of amylase were detected. The amount of ascites was calculated and histological changes of pancreas were observed. The activities of myeloperoxidase (MPO) and levels of malonaldehyde (MDA) in pancreas were determined. The mRNA levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-10, intercellular adhesion molecule (ICAM-1), E selectin and nuclear factor (NF)-kappaB p65 in pancreas were measured by reverse transcription-polymerase chain reaction (RT-PCR). The expression of NF-kappaB p65 protein was also measured by immunohistochemistry. RESULTS: Compared with the AP group, the pathological scores of the LXA(4)-ME group improved (12 h: 8.7 +/- 1.3 vs 11.3 +/- 1.5, 24 h: 7.8 +/- 1.1 vs 11.7 +/- 0.8) and the amount of ascites was lower(12 h: (6.88 +/- 1.23) ml vs (12.32 +/- 1.94) ml, 24 h: (6.53 +/- 0.91) ml vs (14.15 +/- 1.68) ml, all P < 0.01). The serum levels of amylase in the LXA(4) ME group were significantly lower than those in the AP group respectively at 12 h and 24 h post-operation (all P < 0.01). The activity of MPO and the level of MDA in pancreas in the LXA(4)-ME group were significantly lower than those in the AP group (all P < 0.01). The pancreatic expressions of TNF-alpha mRNA, IL-1beta mRNA, ICAM-1 mRNA, E-selectin mRNA and NF-kappaB p65 mRNA at 12 h and 24 h decreased in the LXA(4)-ME group versus the AP group at the corresponding time points (all P < 0.01)while the expression of IL-10 mRNA increased versus the AP group at the corresponding time points (all P < 0.01). Compared with that in the AP group, the pancreatic expression of NF-kappaB p65 protein decreased in the LXA(4)-ME group (12 h: 24.8% +/- 3.0% vs 45.3% +/- 3.4%, 24 h: 31.6% +/- 3.0% vs 48.1% +/- 4.6%, both P < 0.01). CONCLUSION: LXA(4)-ME exerts protective effects in AP rats. And its mechanism may be due to the suppression of NF-kappaB activation. PMID- 22781578 TI - Prevalence and genotypes of Toxoplasma gondii in pork from retail meat stores in Eastern China. AB - Pork is known as one of the most important sources of Toxoplasma gondii infection in China. In the present study, 416 fresh pork samples were collected from different locations of Anhui province, Eastern China. Tissue fluid ELISA was conducted to detect the antibodies to T. gondii. Real-time PCR and bioassay were performed to identify the presence of T. gondii DNA and viable parasites, respectively. Seventy-five out of 416 samples (18.03%) demonstrated real-time PCR positive reaction and 42 out of 416 samples (10.1%) showed tissue fluid ELISA positive reaction. One isolate (Tgpkfx171) was obtained through bioassay in mice from 14 samples that demonstrated both PCR and ELISA positive reaction. The isolate and seven positive DNA samples were genotyped using 9 PCR-RFLP markers including SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico. Among these, only the isolate and two positive DNA samples were genotyped with complete data for all loci, belonging to ToxoDB#9 (Chinese 1) and ToxoDB#213, respectively. This is the first report of the prevalence and genetic typing of T. gondii from pork in retail meat stores in China. The present results provide an accurate picture of the risk of exposure to T. gondii in retail pork in China. PMID- 22781579 TI - TRI12 based quantitative real-time PCR assays reveal the distribution of trichothecene genotypes of F. graminearum and F. culmorum isolates in Danish small grain cereals. AB - Quantitative real-time PCR assays, based on polymorphisms in the TRI12 gene of the trichothecene pathway, were developed to identify and quantify the trichothecene genotypes producing 3-acetyl-deoxynivalenol (3ADON), 15-acetyl deoxynivalenol (15ADON) or nivalenol (NIV) in the Fusarium graminearum species complex, Fusarium culmorum, Fusarium cerealis and Fusarium pseudograminearum. These assays were applied on a total of 378 field samples of cereal grain of wheat, barley, triticale, rye and oats collected from 2003 to 2007 to study the trichothecene genotype composition in Danish cereals. The three genotypes, 3ADON, 15ADON and NIV were found in all five cereal species, great annual variation in the occurrence of the trichothecene genotypes was evident with considerable variation between the samples. 3ADON was the dominant genotype in barley, triticale, rye and oats while 15ADON was most dominant in wheat. The NIV genotype was found at low levels in most samples. Study of genotype composition within the Danish F. graminearum and F. culmorum population was based on principal component analysis (PCA). PCA revealed that the dominating genotype of F. graminearum in wheat is 15ADON. For barley, the PCA analysis indicated that the F. graminearum population consisted of all three genotypes, and in triticale, the F. graminearum population consisted mainly of 15ADON genotype. F. culmorum/F. cerealis showed correlation to the NIV genotype in wheat and triticale but not in barley. F. culmorum/F. cerealis also showed some correlation to 3ADON especially in wheat and triticale. Selected wheat and barley samples from 1957 to 2000 showed low amounts of F. graminearum and F. culmorum in general but with a dominance of the 3ADON genotype. 15ADON was not detected in these samples, except for very low amounts in the sample representing the years from 1997 to 2000. Detection of low amounts of the 15ADON genotype in these historical samples and the relatively high amounts of 15ADON genotype in 2003 and following years correspond well with the occurrence of F. graminearum and indicates that the 15ADON genotype was introduced along with F. graminearum around 2000. The amounts of the 3ADON and 15ADON genotypes correlated well with the total amount of DON whereas the amounts of NIV genotype correlated well with the amount of NIV in wheat and triticale but not in barley where the results indicate that Fusarium poae may also contribute to the NIV content. PMID- 22781580 TI - Harmonization of description and classification of fetal observations: achievements and problems still unresolved: report of the 7th Workshop on the Terminology in Developmental Toxicology Berlin, 4-6 May 2011. AB - This article summarizes the 7th Workshop on the Terminology in Developmental Toxicology held in Berlin, May 4-6, 2011. The series of Berlin Workshops has been mainly concerned with the harmonization of terminology and classification of fetal anomalies in developmental toxicity studies. The main topics of the 7th Workshop were knowledge on the fate of anomalies after birth, use of Version 2 terminology for maternal-fetal observations and non-routinely used species, reclassification of "grey zone" anomalies and categorization of fetal observations for human health risk assessment. The paucity of data on health consequences of the postnatal permanence of fetal anomalies is relevant and further studies are needed. The Version 2 terminology is an important step forward and the terms listed in this glossary are considered also to be appropriate for most observations in non-routinely used species. Continuation of the Berlin Workshops was recommended. Topics suggested for the next Workshop were grouping of fetal observations for reporting and statistical analysis. PMID- 22781581 TI - Scratching the Surface? The use of surface scanning in physical and paleoanthropology. AB - As virtual anthropology is becoming more and more ubiquitous, so are the means to acquire, process and analyze 3D data. Among these means, surface scanners have gained a prominent place for a variety of reasons that make them useful to anthropologists. While surface scanning has several advantages over other 3D devices (digitizers, volume scanners etc.), it does come with one obvious drawback - internal structures remain invisible. Still, surface scanning is emerging as a convenient tool for anthropometric and especially paleoanthropological research. It extends our ability to quantify phenotypic variation, its non-destructive nature contributes to specimen conservation, and it can become an integral part of virtual anthropology, thus doing more than just "scratching the surface". PMID- 22781582 TI - The first modern Europeans. AB - The discovery of new human fossil remains is one of the most obvious ways to improve our understanding of the dynamics of human evolution. The reanalysis of existing fossils using newer methods is also crucial, and may lead to a reconsideration of the biological and taxonomical status of some specimens, and improve our understanding of highly debated periods in human prehistory. This is particularly true for those remains that have previously been studied using traditional approaches, with only morphological descriptions and standard calliper measurements available. My own interest in the Uluzzian, and its associated human remains grew from my interest in applying recently developed analytical techniques to quantify morphological variation. Discovered more than 40 years ago, the two deciduous molars from Grotta del Cavallo (Apulia, Italy) are the only human remains associated with the Uluzzian culture (one of the main three European "transitional" cultures). These teeth were previously attributed to Neanderthals. This attribution contributed to a consensus view that the Uluzzian, with its associated ornament and tool complexes, was produced by Neanderthals. A reassessment of these deciduous teeth by means of digital morphometric analysis revealed that these remains belong to anatomically modern humans (AMHs). This finding contradicts previous assumptions and suggests that modern humans, and not Neanderthals, created the Uluzzian culture. Of equal importance, new chronometric analyses date these dental remains to 43,000-45,000 cal BP. Thus, the teeth from Grotta del Cavallo represent the oldest European AMH currently known. PMID- 22781583 TI - Buccal dental microwear analyses support greater specialization in consumption of hard foodstuffs for Australopithecus anamensis. AB - Molar occlusal microwear texture and anisotropy analyses of 3 Australopithecus anamensis fossil specimens have shown complexity values similar to those of Au. afarensis, indicating that neither of these hominin species had a diet dominated by hard food. However, many researchers have suggested that these were some of the earliest hominins to have such diets. Here we examine buccal microwear patterns of 5 Au. anamensis, 26 Au. afarensis, 48 Hominoidea and 80 Cercopithecoidea primate specimens for independent evidence of dietary adaptations of Au. anamensis. The buccal microwear results obtained suggest that the diet of Au. anamensis relied heavily on hard, brittle food, at least seasonally. This is similar to the diet of the extant Cercopithecoidea primates, including Papio anubis and Chlorocebus aethiops, both of which live in wooded, seasonal savannah environments and have diets that include fruit and grasses, but also underground storage organs (USOs), such as corms or blades, as well as leaves and seeds, and also Mandrillus and Cercocebus, from forested environments with frugivorous-granivorous diets. Furthermore, the buccal microwear patterns of Au. anamensis and Au. afarensis clearly differed - in clear contrast to occlusal enamel texture observations-, which support previous dietary interpretations based on both anatomical and palaeocological reconstructions. PMID- 22781584 TI - Studing cranial vault modifications in ancient Mesoamerica. AB - The artificial modification of infant cranial vaults through massages or by means of constriction and compression devices constitutes a readily visible, permanent body modification that has been employed cross-culturally to express identity, ethnicity, beauty, status and gender. For those ancient societies that staged head shaping, these cultural correlates may be ascertained by examining cranial shapes together with other data sets from the archaeological record. Studies of skulls modified for cultural reasons also provide important clues for understanding principles in neural growth and physiopathological variation in cranial expansion. This paper focuses on head shaping techniques in Mesoamerica, where the practice was deeply rooted and widespread before the European conquest. It provides a comprehensive review of the Mesoamericanistic research on shaping techniques, implements and taxonomies. An up-dated, interdisciplinary examination of the physiological implications and the cultural meanings of artificially produced head shapes in different times and culture areas within Mesoamerica leads to a discussion of the scope, caveats, and future directions involved in this kind of research in the region and beyond. PMID- 22781585 TI - The frontal bone in the genus Homo: a survey of functional and phylogenetic sources of variation. AB - The frontal bone is a useful aspect of the craniofacial skeleton to study in physical anthropology because it contains several characters considered to be important for both population- and species-level distinctions. These include forehead (frontal squama) inclination and supraorbital morphology. Because it lies at the interface between the anterior neurocranium and the upper face, it is also informative about the evolution of both of these regions of the skull. Previous research on frontal bone morphology can be grouped into two broad categories. One set of studies explored the relationship between craniofacial structure and function in an attempt to explain biological sources of variation in the torus development of various extant primate species, including modern humans. The second group of studies examined geographical and temporal patterns of variation in frontal morphology to make inferences about the phylogenetic relationship relationships among fossil hominin populations in the Pleistocene. This paper offers a review of both phylogenetic and functional studies of variation in frontal bone morphology, and synthesizes them to offer a comprehensive understanding of what the frontal bone can tell us about bio behavioral and evolutionary differences both among extant and extinct members of the genus Homo. PMID- 22781586 TI - Gene transfer to the developing mouse inner ear by in vivo electroporation. AB - The mammalian inner ear has 6 distinct sensory epithelia: 3 cristae in the ampullae of the semicircular canals; maculae in the utricle and saccule; and the organ of Corti in the coiled cochlea. The cristae and maculae contain vestibular hair cells that transduce mechanical stimuli to subserve the special sense of balance, while auditory hair cells in the organ of Corti are the primary transducers for hearing. Cell fate specification in these sensory epithelia and morphogenesis of the semicircular canals and cochlea take place during the second week of gestation in the mouse and are largely completed before birth. Developmental studies of the mouse inner ear are routinely conducted by harvesting transgenic embryos at different embryonic or postnatal stages to gain insight into the molecular basis of cellular and/or morphological phenotypes. We hypothesize that gene transfer to the developing mouse inner ear in utero in the context of gain- and loss-of-function studies represents a complimentary approach to traditional mouse transgenesis for the interrogation of the genetic mechanisms underlying mammalian inner ear development(6). The experimental paradigm to conduct gene misexpression studies in the developing mouse inner ear demonstrated here resolves into three general steps: 1) ventral laparotomy; 2) transuterine microinjection; and 3) in vivo electroporation. Ventral laparotomy is a mouse survival surgical technique that permits externalization of the uterus to gain experimental access to the implanted embryos. Transuterine microinjection is the use of beveled, glass capillary micropipettes to introduce expression plasmid into the lumen of the otic vesicle or otocyst. In vivo electroporation is the application of square wave, direct current pulses to drive expression plasmid into progenitor cells. We previously described this electroporation-based gene transfer technique and included detailed notes on each step of the protocol(11). Mouse experimental embryological techniques can be difficult to learn from prose and still images alone. In the present work, we demonstrate the 3 steps in the gene transfer procedure. Most critically, we deploy digital video microscopy to show precisely how to: 1) identify embryo orientation in utero; 2) reorient embryos for targeting injections to the otocyst; 3) microinject DNA mixed with tracer dye solution into the otocyst at embryonic days 11.5 and 12.5; 4) electroporate the injected otocyst; and 5) label electroporated embryos for postnatal selection at birth. We provide representative examples of successfully transfected inner ears; a pictorial guide to the most common causes of otocyst mistargeting; discuss how to avoid common methodological errors; and present guidelines for writing an in utero gene transfer animal care protocol. PMID- 22781588 TI - Trepopnea due to amiodarone-induced diffuse alveolar hemorrhage. PMID- 22781587 TI - Let-7b regulates the expression of the growth hormone receptor gene in deletion type dwarf chickens. AB - BACKGROUND: A deletion mutation in the growth hormone receptor (GHR) gene results in the inhibition of skeletal muscle growth and fat deposition in dwarf chickens. We used microarray techniques to determine microRNA (miRNA) and mRNA expression profiles of GHR in the skeletal muscles of 14-day-old embryos as well as 7-week old deletion-type dwarf and normal-type chickens. Our aim was to elucidate the miRNA regulation of GHR expression with respect to growth inhibition and fat deposition. RESULTS: At the same developmental stages, different expression profiles in skeletal muscles of dwarf and normal chickens occurred for four miRNAs (miR-1623, miR-181b, let-7b, and miR-128). At different developmental stages, there was a significant difference in the expression profiles of a greater number of miRNAs. Eleven miRNAs were up-regulated and 18 down-regulated in the 7-week-old dwarf chickens when compared with profiles in 14-day-old embryos. In 7-week-old normal chickens, seven miRNAs were up-regulated and nine down-regulated compared with those in 14-day-old embryos. In skeletal muscles, 22 genes were up-regulated and 33 down-regulated in 14-day-old embryos compared with 7-week-old dwarf chickens. Sixty-five mRNAs were up-regulated and 108 down regulated in 14-day-old embryos as compared with 7-week-old normal chickens. Thirty-four differentially expressed miRNAs were grouped into 18 categories based on overlapping seed and target sequences. Only let-7b was found to be complementary to its target in the 3' untranslated region of GHR, and was able to inhibit its expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis and quantitative polymerase chain reactions indicated there were three main signaling pathways regulating skeletal muscle growth and fat deposition of chickens. These were influenced by let-7b-regulated GHR. Suppression of the cytokine signaling 3 (SOCS3) gene was found to be involved in the signaling pathway of adipocytokines. CONCLUSIONS: There is a critical miRNA, let-7b, involved in the regulation of GHR. SOCS3 plays a critical role in regulating skeletal muscle growth and fat deposition via let-7b-mediated GHR expression. PMID- 22781589 TI - Diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) to detect anti skin autoantibodies in autoimmune blistering skin diseases: a systematic review and meta-analysis. AB - BACKGROUND: Systematic reviews and meta-analysis are essential tools to accurately and reliably summarize evidence, and can be used as a starting point for developing practice guidelines for the diagnosis and treatment of patients. AIM: To estimate the diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) to detect anti-BP180 and anti-desmoglein 3 (Dsg3) autoantibodies in the diagnosis of autoimmune blistering skin diseases. METHODS: A Medline search of English written articles, published between 1994 and 2011, reporting data on the sensitivity and specificity of diagnostic tests was conducted using the following search terms: "BP180 autoantibodies", "Dsg3 autoantibodies", and "enzyme linked immunosorbent assay". The selected articles have been evaluated according to the quality of the statistical methods used to calculate diagnostic accuracy (definition of cutoff value, use of ROC curves, and selection of control cases). The meta-analysis was performed using a summary ROC (SROC) curve and a random effect model to independently combine sensitivity and specificity across studies. RESULTS: The search yielded 69 publications on BP180 autoantibodies and 178 on Dsg3 autoantibodies. A total of 30 studies met the inclusion criteria: 17 provided data on the assays to detect autoantibodies to BP180 in a sample of 583 patients with bullous pemphigoid (BP), while 13 studies provided data on the assays to search for anti-Dsg3 autoantibodies in a sample of 1058 patients with pemphigus vulgaris (PV). The 17 studies on BP180 autoantibodies yielded a pooled sensitivity of 0.87 (95% confidence interval (CI) 0.85 to 0.89) and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The area under the curve (AUC) for the SROC curve was 0.988, and the summary diagnostic odds ratio was 374.91 (CI, 249.97 to 562.30). The 13 studies on Dsg3 autoantibodies which met the inclusion criteria, yielded a pooled sensitivity of 0.97 (CI, 0.95 to 0.98), and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The AUC for the SROC curve was 0.995 and the summary diagnostic odds ratio was 1466.11 (95% CI, 750.36 to 2864.61). CONCLUSIONS: Results of the meta-analysis demonstrated that ELISA tests for anti BP180 and anti-Dsg3 autoantibodies have high sensitivity and specificity for BP and PV, respectively, and can be used in daily laboratory practice for the initial diagnosis of autoimmune blistering skin diseases. PMID- 22781590 TI - Tools for critical appraisal of evidence in studies of diagnostic accuracy. AB - Studies of accuracy are often more complex to understand than clinical trials, since there can be more than one outcome and scope (screening, diagnosis, and prognosis) and because results have to be reported in more than one way, than in clinical trials (relative risk or odds ratio). Sensitivity and specificity are common terms for practitioners, but to remember that sensitivity is the "ratio between true positive rate and true positive rate plus false negative rate" may sometime cause some frustration. Moreover, likelihood ratio, predictive values, diagnostic odds ratio, and pre- and post-test probability complicate the framework. To summarize these indexes from multiple studies can be also a little more difficult. However, understanding diagnostic test accuracy from different study results and how to interpret systematic reviews and meta-analysis can help every practitioner improve critical appraisal of evidence about the best use of diagnostic tests. Avoiding complicated mathematical formulas, this paper attempts to explain the meaning of the most important diagnostic indexes and how to read a Forest plot and a summary Receiver Operative Characteristic curve. PMID- 22781591 TI - Infectious complications among individuals with clinical monoclonal B-cell lymphocytosis (MBL): a cohort study of newly diagnosed cases compared to controls. AB - Although the risk of progression from monoclonal B-cell lymphocytosis (MBL) to chronic lymphocytic leukemia (CLL) has been well characterized, it is unknown whether other common complications associated with CLL, such as increased risk of infection, occurs in individuals with MBL. We used the Mayo CLL database to identify cohorts of individuals with newly diagnosed MBL (n=154) or newly diagnosed CLL (n=174) who resided within 50 miles of Mayo Clinic. A cohort of 689 adult patients seen for a general medical examination who resided within 50 miles of Mayo clinic and who enrolled in a case-control study of non-Hodgkin lymphoma (NHL) was used as a comparison cohort. Hospitalization with infection was more common among individuals with MBL (25/154; 16.2%), and CLL (32/174; 18.4%) than controls (18/689; 2.6%). On pooled multivariable Cox proportional hazards analysis of all 1017 patients (controls, MBL and CLL), male sex (hazards ratio (HR)=2.3; P=0.002), major co-morbid health problems (HR=1.7, P=0.04), the presence of CLL (HR=3.2, P<0.001), treatment for progressive CLL (HR=2.4, P=0.001) and the presence of MBL (HR=3.0, P=0.001) were independently associated with risk of hospitalization for infection. These results suggest the risk of serious infection in clinical MBL is substantially greater than the risk of progression requiring treatment. PMID- 22781592 TI - Myeloma cells inhibit non-canonical wnt co-receptor ror2 expression in human bone marrow osteoprogenitor cells: effect of wnt5a/ror2 pathway activation on the osteogenic differentiation impairment induced by myeloma cells. AB - Multiple myeloma (MM) is characterized by the impaired osteogenic differentiation of human mesenchymal stromal cells (hMSCs). Canonical Wnt signaling is critical for the regulation of bone formation, however, recent evidence suggests that the non-canonical Wnt agonist Wnt5a stimulates human osteoblastogenesis through its co-receptor Ror2. The effects of MM cells on non-canonical Wnt signaling and the effect of the activation of this pathway on MM-induced osteoblast exhaustion are not known and were investigated in this study. We found that the osteogenic differentiation of bone marrow hMSCs toward osteoprogenitor cells (PreOB) significantly increased Ror2 expression, and that MM cells inhibit Ror2 expression by PreOB in co-culture by inhibiting the non-canonical Wnt5a signaling. The activation of the non-canonical Wnt pathway in hMSCs by means of Wnt5a treatment and the overexpression of Wnt5 or Ror2 by lentiviral vectors increased the osteogenic differentiation of hMSCs and blunted the inhibitory effect of MM in co-culture. Consistently, Wnt5a inhibition by specific small interfering RNA reduced the hMSC expression of osteogenic markers. Our findings demonstrate that the Wnt5a/Ror2 pathway is involved in the pathophysiology of MM induced bone disease and that the activation of the non-canonical Wnt5a/Ror2 pathway in hMSCs increases osteogenic differentiation and may counterbalance the inhibitory effect of MM cells. PMID- 22781593 TI - Ponatinib suppresses the development of myeloid and lymphoid malignancies associated with FGFR1 abnormalities. AB - Myeloid and lymphoid malignancies associated with fibroblast growth factor receptor-1 (FGFR1) abnormalities are characterized by constitutively activated FGFR1 kinase and rapid transformation to acute myeloid leukemia and lymphoblastic lymphoma. Molecular targeted therapies have not been widely used for stem cell leukemia/lymphoma (SCLL). Ponatinib (AP24534), which potently inhibits native and mutant BCR-ABL, also targets the FGFR family. Using murine BaF3 cells, stably transformed with six different FGFR1 fusion genes, as well as human KG1 cells expressing activated chimeric FGFR1 and five newly established murine SCLL cell lines, we show that ponatinib (<50 nM) can effectively inhibit phosphoactivation of the fusion kinases and their downstream effectors, such as PLCgamma, Stat5 and Src. Ponatinib also significantly extended survival of mice transplanted with different SCLL cell lines. Ponatinib administered at 30 mg/kg daily also significantly delayed, or even prevented, tumorigenesis of KG1 cells in xenotransplanted mice. Furthermore, we demonstrate that ponatinib specifically inhibits cell growth and clonogenicity of normal human CD34+ progenitor cells transformed by chimeric FGFR1 fusion kinases. Overall, our data provide convincing evidence to suggest that pharmacologic inhibition of FGFR1 fusion kinases with ponatinib is likely to be beneficial for patients with SCLL and perhaps for other human disorders associated with dysregulated FGFR1 activity. PMID- 22781594 TI - Suppression of uninvolved immunoglobulins defined by heavy/light chain pair suppression is a risk factor for progression of MGUS. AB - We hypothesized that the suppression of uninvolved immunoglobulin in monoclonal gammopathy of undetermined significance (MGUS) as detected by suppression of the isotype-specific heavy and light chain (HLC-pair suppression) increases the risk of progression to malignancy. This approach required quantitation of individual heavy/light chains (for example, IgGlambda in IgGkappa MGUS patients). Of 1384 MGUS patients from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 999 persons. We identified HLC-pair suppression in 27% of MGUS patient samples compared with 11% of patients with suppression of uninvolved IgG, IgA or IgM. HLC pair suppression was a significant risk factor for progression (hazard ratio (HR), 2.3; 95% confidence interval (CI) 1.5-3.7; P<0.001). On multivariate analysis, HLC-pair suppression was an independent risk factor for progression to malignancy in combination with serum M-spike size, heavy chain isotype and free light chain ratio (HR, 1.8; 95% CI, 1.1-3.00; P=0.018). The finding that HLC-pair suppression predicts progression in MGUS and occurs several years before malignant transformation has implications for myeloma biology. PMID- 22781596 TI - [Pay attention to infections in patients with severe aplastic anemia]. PMID- 22781595 TI - Ulnar nerve injury after a comminuted fracture of the humeral shaft from a high velocity accident: a case report. AB - INTRODUCTION: Injury to the ulnar nerve following humerus shaft fracture is a very rare entity because the ulnar nerve is well protected from the bone by muscle and soft tissue, and thus remains unaffected in these fractures. We report what is, to the best of our knowledge, the first case of ulnar nerve injury due to a comminuted humeral shaft fracture. The injury manifested and was diagnosed the day after a high-velocity accident. The paucity of related literature and the necessity for early diagnosis and subsequent treatment of such injuries in high velocity accidents urged us to document this case. CASE PRESENTATION: A 30-year old Indian man presented to our Emergency Department after a road traffic accident. Our patient complained of right arm pain and the inability to move his extremity. The following morning he developed clawing. Nerve conduction studies on the peripheral nerves of his arm in addition to an X-ray confirmed the diagnosis of a possible injury to the ulnar nerve. Our patient was taken to our Operating Room for surgery, during which a fragment of bone was found abutting the ulnar nerve after penetrating his triceps. This fragment of bone was replaced and the fracture was reduced by open reduction and internal fixation using a dynamic compression plate and screws. Postoperatively, our patient received physical therapy and was discharged two weeks after surgery with no neurological deficit. CONCLUSIONS: This case emphasizes the urgency and importance of careful neurological examination of all the peripheral nerves supplying the arm in patients with a fracture of the shaft of the humerus. In the setting of injury to the arm in high-velocity accidents, a differential diagnosis of ulnar nerve injury should always be considered. PMID- 22781597 TI - [Screen of phosphopeptide specific for acute leukemia]. AB - OBJECTIVE: To screen phosphopeptide specific for acute leukemia. METHODS: Mononuclear cells from bone marrow were collected from 16 newly diagnosed acute lymphoblastic leukemia (ALL) and 20 acute myeloid leukemia (AML) patients. Peptides were extracted and purified, analyzed by immunoprecipitation and liquid chromatography coupled with tandem mass spectrometry (LC-MS). RESULTS: (1) Non receptor tyrosine kinase family members Fyn, Yes, Src widely expressed in acute leukemia; (2) Some phosphopeptides, including non-receptor tyrosine kinase family members Abl/iso1 and Abl, non-receptor Ser/Thr protein kinase family members Bcr, JNK2, JNK2 iso2, Adaptor/scaffold members Cas-L, Cbl, CrkL CENTD1 (Centaurin delta1) ZO2, transcriptor GFR-1 and phosphatase SHIP-2 were detected in Ph positive ALL, but not in other kinds of ALL. (3) Hck, Lyn and Fgr selectively expressed in AML (except AML-M(3)). CONCLUSION: Some phosphopeptides were specific for ALL and AML, and may be useful for diagnosis and therapy of acute leukemia. PMID- 22781598 TI - [One case of acute promyelocytic leukemia with t(9; 22)(q34; q11)]. PMID- 22781599 TI - [Increased susceptibility of recombinant type 2A von Willebrand factor mutant A1500E to proteolysis by ADAMTS13]. AB - OBJECTIVE: To investigate the susceptibility of von Willebrand factor (VWF) type 2A mutant A1500E to proteolysis by metalloprotease ADAMTS13 and to provide the direct supports for the pathogenesis of VWF mutation A1500E responsible for von Willebrand disease (VWD) type 2A. METHODS: Recombinant wild-type VWF (WT-VWF) and A1500E mutant VWF transiently expressed on transfected HeLa cell lines. Expression media were collected and concentrated, then cleaved directly by recombinant ADAMTS13 (rADAMTS13). Compared with WT-VWF, the susceptibility of A1500E mutant VWF to proteolysis by ADAMTS13 was analyzed using SDS-agarose gel VWF multimers analysis. RESULTS: In vitro the expression of VWF:Ag in the supernatants of WT-VWF and A1500E mutant VWF were 1.10 U/ml and 0.78 U/ml, respectively, while VWF:Ag in cells lysates of A1500E mutant VWF was 90.6% of that of WT-VWF. The SDS-agarose gel VWF multimers analysis showed that there were no differences between WT-VWF and A1500E mutant VWF. The A1500E mutant VWF could be efficiently cleaved by ADAMTS13 under static condition without denaturants such as urea and guanidine HCl. VWF multimeric analysis showed that high and intermediate molecular weight multimers dramatically decreased while low molecular weight multimers obviously increased. Conversely, WT-VWF could not be cleaved by ADAMTS13 under the same condition. CONCLUSION: The A1500E mutation resulted in VWF more susceptible to ADAMTS13-dependent proteolysis, which belonged to VWD type 2A group 2 mutation. PMID- 22781600 TI - [A case of p190(bcr-abl) chronic myelocytic leukemia]. PMID- 22781601 TI - [Co-expression of CD99/MIC2 and ALK in anaplastic large-cell lymphoma tissues and its significance]. AB - OBJECTIVE: To investigate co-expression of CD99/MIC2 and anaplastic lymphoma kinase (ALK) protein in anaplastic large-cell lymphoma (ALCL) tissues and Karpas 299 cells and its significance. METHODS: Clinical prognoses and ALK protein expressions of 25 cases of ALCL were reviewed retrospectively, the median duration of survival was analyzed for patients with ALK(+) ALCL and ALK(-) ALCL. Histological and immunohistochemical staining were applied to other 25 cases of ALCL and paraffin-embedded tissue from human anaplastic large-cell lymphoma Karpas 299 cells to detect the protein of CD99 and ALK. RESULTS: Of former 25 cases of ALCL, median duration of survival for ALK(+) patients was 59 months, whereas 20 months for ALK(-) patients. The prognosis of ALK(+) group was better than that of ALK(-) group, survival curves of these two groups showed statistically significant (P < 0.05). CD99 was positive in 18 cases (72.0%) while negative in 7 cases (28.0%) of the latter 25 ALCL, ALK was positive in 19 cases (76.0%) while negative in 6 cases (24.0%); Of 19 ALK(+) ALCL, 16 (84.2%) cases co expressed CD99-ALK; and in 6 ALK(-) ALCL, 2(33.3%) were CD99-ALK double negative, the expression of CD99 protein strongly correlated with that of ALK protein (P < 0.05). ALK and CD99 protein expressed in Karpas 299 cells with diffuse distribution. CONCLUSIONS: CD99 highly expressed in ALCL, and showed high rate of co-expression with ALK. CD99 protein expression could be considered as a helpful diagnostic and prognostic factor of ALCL, especially for ALK(+) ALCL. PMID- 22781602 TI - [Study on imatinib trough concentration, efficacy and their relation in chronic myelocytic leukemia]. AB - OBJECTIVE: To determine plasma imatinib concentration, intracellular imatinib concentration, and hOCT1 and ABCB1 mRNA expression in bone marrow cells of CML patients to further evaluate the potential usefulness of these measures as markers of imatinib efficacy and their clinical relationships. METHODS: Eighty CML patients in chronic phase receiving imatinib were enrolled in this study, including 56 males and 24 females with a median age of 39.5 (6 - 76) years. Imatinib was administered at a median dose of 400 (200 - 800) mg/d orally per day with a median course of 24 (3 - 90) months. The intracellular imatinib concentrations in bone marrow cells of 28 patients were simultaneously determined. Real-time quantitative PCR with a taqman probe was used to assess hOCT1 and ABCB1 mRNA expression on bone marrow cells of 36 patients. Imatinib trough concentration was determined by high-performance liquid chromatography tandem mass spectrometry with a detectability of 2 - 10 000 ug/L. Serum alpha1 acid glycoprotein (AGP) was measured by immune turbidimetry on a BNProspec protein analyzer (Dade Behring, USA). All patients were divided into MMR, CCyR, PCyR or drug-resistant groups according to response. RESULTS: Plasma imatinib trough concentration of 80 patients was (1274.1 +/- 559.1) (109.0 - 3400.0) ug/L. The plasma imatinib trough concentration of 59 (73.8%) patients with a dose of 400 mg/d was (1252.0 +/- 569.5) (109 - 3400) ug/L, including 37 (62.7%) patients with concentrations of more than 1000 ug/L and 9 (15.2%) patients more than 800 ug/L. Plasma imatinib trough concentration in the MMR group ?[(1531.9 +/- 634.1) ug/L?] was significant higher than in the PCyR ?[(812.8 +/- 480.3) ug/L?] or drug resistant group ?[(875.2 +/- 243.1) ug/L?] (P < 0.05). Plasma imatinib trough concentration in the CCyR group ?[(1288.4 +/- 498.2) ug/L?] was significant higher than in the PCyR group (P = 0.027). There was no significant difference between CCyR and MMR groups with regard to plasma imatinib trough concentration (P = 0.136). The intracellular imatinib concentration in bone marrow cells in the CCyR group ?[12.6 (2.4 - 90.4) ug/L?] was significantly higher than drug resistant ?[6.6 (2.6 - 111.0) ug/L?] or PCyR ?[2.7 (2.4 - 4.7) ug/L?] groups (P = 0.013). The hOCT1 mRNA expression on bone marrow cells in the CCyR group ?[25.9(0.7 - 123.9) * 10(-5)?] was significantly higher than in drug-resistant ?[7.8 (2.5 - 33.5) * 10(-5)?] or PCyR ?[4.2 (1.4 - 11.9) * 10(-5)?] groups (P = 0.036). The ABCB1 mRNA expression on bone marrow cells in drug-resistant group ?[136.7 (15.0 - 1604.9) * 10(-5)?] was significantly higher than in CCyR ?[129.1 (12.9 - 783.3) * 10(-5)?] or PCyR ?[34.4 (2.2 -108.2) * 10(-5)?] groups (P = 0.013). Plasma imatinib trough concentration was positively correlated with AGP (r = 0.446, P = 0.000) or dose (r = 0.346, P = 0.002). There were no significant correlations between plasma imatinib trough concentration and height, weight or body surface area (P > 0.05). There were no significant differences among different courses with regard to plasma imatinib trough concentration (P > 0.05). CONCLUSION: Clinical responses in CML patients were correlated with plasma and intracellular imatinib trough concentrations. Imatinib concentration was regulated by AGP and the activities of hOCT1 and ABCB1. PMID- 22781603 TI - [Analysis of plasma trough level of imatinib in Chinese CML patients]. AB - OBJECTIVE: To evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients. METHODS: Plasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated. RESULTS: (1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 +/- 585), (1341 +/- 595) and (1740 +/- 748) ug/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 +/- 571) ug/L vs no CCyR (1354 +/- 689) ug/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients. CONCLUSION: There was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients. PMID- 22781604 TI - [Clinical investigation of primary amyloidosis with autologous hematopoietic stem cell transplantation]. AB - OBJECTIVE: To investigate the treatment of primary amyloidosis with high-dose melphalan and autologous hematopoietic stem cell transplantation to further examine the survival, hematologic response, and improvement of amyloid-related organ dysfunction. METHODS: Retrospective analysis of 20 patients with primary amyloidosis treated with autologous hematopoietic stem cell transplantation. The status of major organ function before transplantation, mobilization programs and conditioning regimen as possible risk factors for survival were also investigated. RESULTS: Of 20 cases, 11 out of 15 evaluable cases achieved hematologic response, among them, 6 got complete remission (CR, 40%) and 5 partial remission (PR, 33%). The median onset time was 3.0 months (1.5 - 4.0 months) and 4 months (3 - 5 months), respectively after transplantation. The overall hematologic response was 73%. The 11 hematologic responders also had kidney responses. The median time to achieve kidney response was 3 months (2 - 6 months). The 3-year overall survival of the cohort of cases was 71.4%. The major causes of death were heart failure, renal dysfunction and gastrointestinal bleeding. G-CSF alone could obtain satisfactory mobilization results and most of patients well tolerated to the conditioning regimen of melphalan doses from 140 mg/m(2) to 200 mg/m(2). CONCLUSION: Treatment of primary amyloidosis with high dose melphalan followed by autologous peripheral blood stem cell transplantation produced high efficacy. The cardiovascular system involvement, renal dysfunction and the abnormality of coagulation function before transplantation may be the risk factors for survival. PMID- 22781605 TI - [Allogeneic peripheral blood stem cell transplantation from sibling donors for 10 patients with multiple myeloma]. AB - OBJECTIVE: To evaluate the efficacy of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from sibling donors for treatment of multiple myeloma (MM). METHODS: Ten patients with MM received allo-PBSCT with conditioning consisting of fludarabine plus melphalan and cyclophosphamide mostly.CsA plus mycophenolate mofetil (MMF) and short-term MTX were applied to prevent graft versus host disease (GVHD) in 8 patients, FK506 plus short-term MTX in other 2 patients. RESULTS: All patients engrafted successfully, the median time for ANC > 0.5 * 10(9)/L was 16 (12 - 24) days, and for BPC > 20 * 10(9)/L 23 (16 - 102) days. Five patients developed acute GVHD, and only one III-IV aGVHD. Of 9 patients, 7 developed chronic GVHD. The transplant-related mortality (TRM) at 100 days was 10% (1/10), mainly from heart and renal failure and severe infection. The 1-year expected overall survival (OS), 1-year disease-free survival (DFS) and relapse rate were 67.5%, 55.56% and 11.11% respectively. Up to now, 6 patients were still alive, of them 1 patient have survived over 99 months after allo PBSCT. CONCLUSION: Young MM patients having HLA-identical sibling donors well tolerated allo-PBSCT based on fludarabine to prolong their OS by reducing TRM, though further work is warranted. PMID- 22781606 TI - [Establishment of xenotransplated mouse model using primary multiple myeloma cells]. AB - OBJECTIVE: To establish xenotransplated mouse model by non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice with primary myeloma cells. METHODS: The model of xenograft was established in NOD/SCID mice by tail vein injection of mononuclear cells from two end stage multiple myeloma patients, three mice were inoculated for each patient. Mice were monitored weekly for body weight. Two weeks later, the human CD45(+) cells from peripheral blood of mice were evaluated by flow cytometry (FCM). The experiment endpoint was body weight loss up to 20% or had pale, vertical hair and listlessness, then spleen and liver were studied by histologic analysis, the human CD45(+)CD38(+) cells from spleen, lymph node, peripheral blood and bone marrow were evaluated by FCM. RESULTS: Body weight of mice in group patient 1 and group patient 2 decreased seven and five weeks after inoculation respectively; the human CD45(+)CD38(+) cells appeared in the peripheral blood (26 +/- 4) and (16 +/- 4) days after inoculation in group patient 1 and group patient 2 respectively, and increased by time, reaching (16.2 +/- 3.0)% and (31.3 +/- 3.5)%, respectively at the endpoint; the spleen, liver and lymph node of both groups enlarged, the typical malignant plasma cells were observed in them. The human CD45(+)CD38(+) cells were detected in spleen, lymph node and bone marrow by FCM. CONCLUSION: Our study successfully established a NOD/SCID mouse model xenotransplated with human primary myeloma cells. PMID- 22781607 TI - [A novel diagnostic measure of platelet-specific antibody in immune thrombocytopenia]. AB - OBJECTIVE: To detect the platelet glycoprotein-specific antibodies in serum of thrombocytopenia patients and evaluate its diagnostic value for immune thrombocytopenia. METHOD: Anti-GPIIb/IIIa, GPIb/IX and GPIa/IIa antibodies were assayed by ELISA kit (PAKUTO) in patients with thrombocytopenia. RESULTS: The sensitivity and specificity of PAKAUTO in immune thrombocytopenia were 44.0% and 95.7%, respectively. The values of positive and negative predictions were 98.0% and 26.2%, respectively. Among those PAKAUTO positive patients, positive rates of GPIIb/IIIa, GPIa/IIa and GPIb/IX were 87%, 35% and 10%, respectively. The positive rate of patients not received immune suppressive agents (58.5%) was significantly higher than those received immune suppressive agents (26.9%) (P < 0.01). The positive rate of patients with platelet count <= 20 * 10(9)/L (51.6%) was significantly higher than those with platelet count > 20 * 10(9)/L (27.8%) (P < 0.01). The positive rate of patients with secondary immune thrombocytopenia (66.7%) was significantly higher than those with primary immune thrombocytopenia (41.7%) (P < 0.05). CONCLUSION: The highly specific method (PAKAUTO) could effectively differentiate immune or non-immune thrombocytopenia and be applied to diagnosis of immune thrombocytopenia. PMID- 22781608 TI - [Clinical efficacy of lower dose rituximab for chronic refractory immune thrombocytopenic purpura]. AB - OBJECTIVE: To investigate the efficacy and safety as well as the effects of lower dose of rituximab on B-lymphocytes, serum immunoglobulin, and platelet glycoprotein-specific antibodies in patients with chronic refractory immune thrombocytopenic purpura (ITP). METHODS: Twenty chronic refractory ITP patients, median age 47 (20 to 60) years old, received intravenous rituximab at the dose of 100mg once weekly for 4 consecutive weeks. Laboratory studies included complete blood cell count, regular monitoring of liver and kidney functions, blood coagulation and serum concentrations of IgG, IgM and IgA. CD3(+), CD4(+), CD8(+), CD19(+), CD20(+) cell numbers were assayed by flow cytometry prior to and following rituximab. Platelet glycoprotein antibodies were detected by ELISA. The detection of indicators were compared by paired T test, with P < 0.05 as statistically significant. RESULTS: There was significant difference of the average platelet count between prior- ?[(13 +/- 5) * 10(9)/L?] and post-treatment ?[(124 +/- 106) * 10(9)/L?] with lower dose rituximab (P < 0.01). Reaching PLT peak period was of (24 +/- 7) d with median time of 18 d. The responses were of 11(55%) CR, 4 (20%) R and 5 (25%) NR, respectively, with median response duration of 8 months (5 - 23 months). There were no significant changes of peripheral blood white blood cell count, hemoglobin, serum immunoglobulin, as well as CD3(+), CD4(+), CD8(+) lymphocyte counts during prior- and post-treatment. CD19(+)/CD20(+) cells were almost depleted in all patients ?[(125.65 +/- 14.12) * 10(6)/L vs (50.53 +/- 29.11) * 10(6)/L, P < 0.01)?]. Expectedly, three cases of positive detection of platelet antibodies were negative after 4 weeks of lower dose of rituximab; one patient experienced infusion-related reaction. CONCLUSION: Treatment with lower dose rituximab may be an effective and safe approach in patient with chronic refractory ITP. However, the optimal therapeutic schedule, long-term efficacy and adverse events need further investigation. PMID- 22781609 TI - [The immune effects of rituximab on dendritic cells derived from patients with primary immune thrombocytopenia]. AB - OBJECTIVE: To explore the changes of surface antigen and function of rituximab on dendritic cells derived from patients with Primary immune thrombocytopenia (ITP) to further understand the effective mechanism of immunotherapy. METHODS: The peripheral blood mononuclear cells (PBMCs) were isolated from remission patients with ITP before and after low-dose rituximab infusion, and the PMNCs were stimulated for 5 days by rhGM-CSF and rhlL-4 in 5% CO2 air at 37 degrees C incubator. Then all of DCs were cultured with TNF-alpha for 48 hours. The morphology of DCs was monitored under inverted microscope daily, and the surface antigens of the DCs were analysed by flow cytometry, meanwhile the levels of IL 12p70 and TGF-beta1 in supernatants were detected by ELISA, mix lymphocyte reaction was performed by MTT assay. RESULTS: (1) Rituximab-treated-DCs showed no obvious tree-like protruding compared with untreated-DCs. The former cells were small and most of nucleus were centric. (2) The expressions of HLA-DR, CD80, CD83 and CD86 on rituximab-treated-DCs ?[56.37 +/- 3.95)%, (36.41 +/- 2.82)%, (30.45 +/- 4.61)% and (41.98 +/- 4.17)%, respectively?] were significantly lower than those untreated-DCs ?[(73.71 +/- 7.61)%, (55.14 +/- 7.30)%, (80.91 +/- 7.09)% and (59.03 +/- 3.43)%, respectively?](all P < 0.05), the concentration of IL-12p70 was significantly lower, ?[(66.87 +/- 4.29)% vs (50.17 +/- 14.52)%?], while that of TGF-beta1 ?[(9.70 +/- 0.31)%?] higher than the untreated-DCs ?[(2.70 +/- 0.36)%?] (P < 0.05). (3) The abilities to activate T cells proliferation of rituximab-treated-DCs reduced compared with untreated-DCs. CONCLUSION: The surface antigen of ITP-DCs and the concentration of IL-12p70 reduced after the low-dose rituximab infusion. The abilities to activate T cells proliferation reduced while the concentration of TGF-beta1 increased. Rituximab may achieve its therapeutic effect on ITP by downregulating the immunoreactivity of DCs. PMID- 22781610 TI - [Detecting acetylated proteins by affinity chromatography column]. AB - OBJECTIVE: To establish a rapid, relatively quantitative method of detecting acetylated proteins. METHODS: The proteins of Jurkat cells were acetylated by Trichostatin A (TSA) at different concentrations, then enriched and purified by anti-acetylated lysine antibodies affinity chromatography colum. The components eluted by acid were fixed on the microplate, the levels of acetylated proteins were tested by ELISA, and their components were identified by MALDI-TOF-TOF mass spectrometry. Also the above-mentioned methods were applied to the other three agents (gallic acid, emodin and monoacetylated emodin A). RESULTS: That 4 * 10(5) Jurkat cells treated with 1 umol/L TSA produced the optimal acetylated effect, up to 22 acetylated proteins were identified by MALDI-TOF-TOF, of them 15 were acetylated histones. The other three agents also induced acetylation, the relative values of acetylated proteins of Jurkat cells treated with 35.09 umol/L and 17.54 umol/L gallic acid were 4.3% and 14.2% respectively; those as of 28.7% and 11.5% treated with 1.47 umol/L and 2.94 umol/L emodin; those as of 22.0% and 3.6% treated with 152.91 umol/L and 30.58 umol/L monoacetylated emodin A. CONCLUSION: The method based on affinity chromatography colum may be useful for the detection of acetylated proteins, and could be used to screen agents which target to histone deacetylase. PMID- 22781611 TI - [Effect of UC-MSCs on inflammation and thrombosis of the rats with collagen type II induced arthritis]. AB - OBJECTIVE: To investigate the immunoregulation effects of umbilical cord mesenchymal stem cells (UC-MSCs) on the rats with collagen II induced arthritis (CIA). METHODS: The rats were first immunized by intradermal injection of chicken collagen type II emulsified with complete Freund's adjuvant (CFA) to monitor their swelling of foot, hair color and action state. After injected UC-MSC by caudal vein, the rats were scored with the arthritis index (AI) once a week. Then, the concentration of interleukin (IL-6), tumor necrosis factor-alpha (TNF alpha) in serum and D-dimer (D-D), antithrombin-III (AT-III), thrombomodulin (TM) in plasma were detected by ELISA. RESULTS: Obvious swellings of the feet were found in the experiment group compared with normal one. ELISA analysis showed that the concentrations of IL-6, TNF-alpha, D-D and TM in plasma of the experiment group as of (200.48 +/- 15.04) ng/L, (450.25 +/- 45.39) ng/L, (274.26 +/- 67.93) ng/L and (9.18 +/- 0.84) ug/L, respectively were higher than of(167.62 +/- 0.97) ng/L, (371.44 +/- 21.26) ng/L, (193.95 +/- 8.22) ng/L and (6.30 +/- 0.32) ug/L respectively in normal group (P < 0.05), but the concentration of AT III ?[(89.57 +/- 6.40) ng/L?] was lower than normal group ?[(112.82 +/- 1.74) ng/L?] (P < 0.05). The levels of cytokines through the UC-MSCs treatment were significantly different from the model group (P < 0.05). After 9 weeks, these cytokines in the UC-MSCs group were mostly the same as the normal group. CONCLUSION: The thrombophilia status of the CIA rats was caused by immune injury. The UC-MSCs reduced the production of inflammatory cytokines and regulated and repaired the balance of coagulation and anticoagulation system of the body to cure the immune-related thrombophilia. PMID- 22781612 TI - [The role of Src kinase inhibitor ZD6474 on multi-drug resistant K562/A02 cells]. AB - OBJECTIVE: To investigate the role of Src kinase inhibitor ZD6474 on the growth of multidrug-resistant K562/A02 cells and its regulatory mechanisms. METHODS: The possible mechanisms of drug-resistance were tested by Western blot. Proliferation assays and cell cycle distribution were analyzed by WST metric analysis. Western blot were used to investigate the mechanisms of antiproliferative activity induced by tyrosine kinase inhibitor ZD6474. The in vivo anti-tumor activity was evaluated in K562, K562/A02 xenografted nude mice by administration of ZD6474 (25 - 100 mg*kg(-1)*d(-1), PO). RESULTS: Compared with parental K562 cells, marked high levels of p-Src and Src expression were detected in K562/A02 cells. WST results showed that the IC(50) values of ZD6474 on K562 and K562/A02 after 48 hours incubation were (1.61 +/- 0.07) umol/L and (3.22 +/- 0.21)umol/L, respectively. ZD6474 caused an accumulation of cells in the G(0)/G(1) fraction and apoptosis by inhibiting the expressions of p-Src and Src kinase. Administration of ZD6474 produced a dose-dependent inhibition of tumor growth. 50 mg/kg ZD6474 produced the growth inhibition rates of 43.7% and 56.3%, respectively in K562 and K562/A02. CONCLUSION: Our results indicated that inhibiting Src kinase could induce K562/A02 cells apoptosis in vitro and in vivo. PMID- 22781613 TI - [The effects of imatinib mesylate on immune globulin and T cell subset in patients with chronic myelocytic leukemia]. PMID- 22781614 TI - [Haploidentical hematopoietic stem cell transplantation for treatment of T lymphoblastic lymphoma with chronic myeloid leukemia: a case report and literature review]. PMID- 22781615 TI - [Role of high-dose cytarabine as consolidation therapy for cytogenetically intermediate AML: a single center analysis]. PMID- 22781616 TI - [A preliminary study on the relationship between EZH2 and microRNA-101 and the prognostic role of EZH2 in acute myeloid leukemia]. PMID- 22781617 TI - [The study of acquired vitamin K-dependent coagulation factors deficiency in 92 patients with coagulation disorders]. PMID- 22781618 TI - [Comparative proteomics research of HL-60 cell differentiation initiation induced by dimethylsulfoxide]. PMID- 22781620 TI - [Cotransplant of HLA haploidentical peripheral blood stem cells and mesenchymal stem cells to treat a child with severe aplastic anemia]. PMID- 22781619 TI - [Rapamycin treatment of recurrent autoimmune hemolytic anemia in 28 cases]. PMID- 22781621 TI - [Tumor necrosis factor-alpha targeted therapy for graft verous host disease]. PMID- 22781622 TI - [Myeloma bone disease: pathogenetic mechanisms and targeted therapy]. PMID- 22781623 TI - [Case report: two cases of a novel Bunyavirus-associated hemophagocytic lymphohistiocytosis]. PMID- 22781624 TI - [Adrenal extramedullary hematopoiesis associated with hereditary spherocytosis: report of a case]. PMID- 22781625 TI - [Expert panel consensus statement on prevention and standardized treatment of drug-induced liver injury in patients with blood diseases]. PMID- 22781626 TI - An experimental estimate of the relative aromaticity of the cyclooctatetraene dianion by fusion to dimethyldihydropyrene. AB - The synthesis of the cyclooctatetraene dianion (COT(2-)) fused at the [e] position of trans-10b,10c-dimethyl-10b,10c-dihydropyrene (DHP) is described, and by comparison of (1)H NMR properties and NICSAv to the analogous benzene fused DHP, the relative aromaticity of the dianion is found to be at least as great as that of benzene, and substantially larger than that of the cyclopentadienide anion. PMID- 22781627 TI - NAD induces astrocyte calcium flux and cell death by ART2 and P2X7 pathway. AB - Mono-ADP-ribosyltransferase 2 (ART2) is found in mouse T cells and has mediated NAD-induced cell death (NICD) alongside the P2X7 pathway. We determined whether ART2 was expressed in mouse brain astrocytes and the possible function of the NAD ART2-P2X7 pathway in astrocytes. Our results demonstrate that ART2 existed both in cultured mouse astrocytes and mouse brain slices. Exposure of astrocytes to the ART2 substrate, NAD, induced calcium elevation, which was blocked by ART2 and P2X7 inhibitors. ATP and NAD had an additive effect on calcium elevation. NICD in low-calcium conditions was blocked by ART2 and P2X7 inhibitors. The harmful effect of ATP on astrocytes was inhibited by P2X7 and ART2 inhibitors, meaning that endogenous NAD release may occur. Both NICD function and oxygen-glucose deprivation injury in mouse brain slices were also involved in the ART2-P2X7 pathway. Collectively, to our knowledge, our study provides the first evidence that ART2 exists in mouse brain astrocytes and NAD induces calcium elevation and astrocyte death by an ART2 and P2X7-mediated mechanism. The results suggest a novel approach for manipulating astrocyte death. PMID- 22781628 TI - Education-to-job mismatch and the risk of work injury. AB - OBJECTIVES: To examine the association between education-to-job mismatch and work injury. METHODS: Cross-sectional data from the 2003 and 2005 Canadian Community Health Surveys (n=63,462) were used to examine the relationship between having an educational level that is incongruent with occupational skills requirements and the risk of sustaining a work injury requiring medical attention or a work related repetitive movement injury (RMI). The effect on injury of the interaction of overeducation with recent immigrant status was also examined. Models were stratified by sex and adjusted for possible confounders. Occupational physical demands were conceptualised as a potential mediating variable. RESULTS: After adjustment for covariates, over-education was associated with work injury and RMI for both sexes. Adjustment for occupational demands attenuated the impact on work injury but did not eliminate the effect on RMI among men. The interaction of over education and recent immigrant status resulted among men in a fourfold increase in the odds of work injury compared with non-recent immigrants who were not over educated. After adjustment for occupational demands, over-educated recent immigrant men still had more than a twofold increase in the odds of injury. CONCLUSIONS: The risk of sustaining a work injury is higher among those whose education exceeds that of job requirements. These findings highlight the need to address barriers to suitable employment, particularly among recent immigrants. PMID- 22781629 TI - Return to pre-injury health status and function 12 months after hospitalisation for sport and active recreation related orthopaedic injury. AB - BACKGROUND: Hospitalised sport and active recreation injuries can have serious long-term consequences. Despite this, few studies have examined the long-term outcomes of these injuries. The purpose of this study was to establish whether patients hospitalised with orthopaedic sport and active recreation injuries, have returned to their pre-injury levels of health status and function, 12 months post injury and identify factors associated with poor outcomes. The present work was a cohort study with retrospective assessment of pre-injury status and prospective assessment of outcome at 12 months post injury. METHODS: Adults with orthopaedic sport and active recreation injuries, captured by the Victorian Orthopaedic Trauma Outcomes Registry were recruited to the study. Pre-injury and 12-month outcomes were assessed using the 36-item Short Form Health Survey (SF-36) and the extended Glasgow Outcome Scale. Differences in pre-injury and post-injury SF-36 scores were examined and demographic, injury, hospital and physical activity variables were assessed for associations with outcome using multivariate linear regression. RESULTS: Of the 324 participants 98% were followed-up at 12 months post injury. At 12 months, participants reported a mean 7.0-point reduction in physical health (95% CI 5.8 to 7.8) and a 2.5-point reduction in mental health (95% CI 1.2 to 3.0), with 58% (95% CI 52.6% to 63.4%) reporting reduced function. Sporting group (p=0.001), Injury Severity Score >15 (p=0.007) and high pre-injury vigorous activity levels (p=0.04), were related to poorer physical health outcomes. CONCLUSIONS: At 12 months post injury, most participants reported large reductions in physical health and reduced function. This information is important for furthering our understanding of the burden of sport and active recreation injury and setting priorities for treatment and rehabilitation. PMID- 22781630 TI - Imaging spectrum of thoracic melioidosis. AB - Melioidosis is predominantly a tropical disease caused by Burkholderia pseudomallei, a soil-dwelling gram-negative, aerobic bacillus that is distributed primarily in southeast Asia and northern Australia. In this pictorial essay, we provide an illustrated review and conceptual framework of the protean imaging features of this infection, along with a brief description of its clinical manifestations and demographic features. PMID- 22781631 TI - Altered phenotype in peripheral blood and tumor-associated NK cells from colorectal cancer patients. AB - Despite NK cells being originally identified because of their ability to kill tumor cells in vitro, only limited information is available on NK cells infiltration of malignant tumors, especially in humans. NK cells infiltrating human colorectal carcinomas (CRCs) were analyzed to identify their potential protective role in an antitumor immune response. The expression and function of relevant molecules were analyzed from different sources, comparing tumor associated NK cells (TANKs) with autologous peripheral blood NK cells (PB-NKs) from CRC patients-the latter in comparison with PB-NKs from normal donors. TANKs displayed a profound alteration of their phenotype with a drastic reduction of NK cell receptor expression. Co-culture experiments showed that CRC cells produce modulation in NK phenotype and functionality. Moreover, PB-NKs from CRC patients also exhibited an altered phenotype and profound defects in the ability to activate degranulation and IFN-gamma production. For the first time, TANK and PB NK cells from CRC patients have been characterized. It is shown that they are not capable of producing relevant cytokines and degranulate. Taken together, our results suggest that NK cells from CRC patients present alterations of phenotype and function therefore supporting the progression of cancer. PMID- 22781632 TI - Simultaneous blood pressure measurement in both arms in hypertensive and nonhypertensive adult patients. AB - BACKGROUND: When blood pressure (BP) is taken for the first time, it should be measured in both arms; follow-up measurements should be taken in the arm with the highest BP. However, in clinical practice, this recommendation is rarely followed. OBJECTIVE: Identify the degree of differences in BP between the right and the left arm in individuals with normal and high BP. METHODS: We measured BP in 111 hypertensive and 80 normotensive patients in both arms at the same time using identical Omron HEM 725 CIC automatic sphygmomanometers. The devices were then switched to the other arm and another set of readings was taken. The absolute and relative difference in BP between arms was calculated from the average of these two readings. We categorized differences as at least 5, at least 10, and at least 20 mmHg for systolic blood pressure/diastolic blood pressure (SBP/DBP). RESULTS: The BP was higher in the right arm, with no statistical significance. The relative differences were also not significant: SBP 1.1+/-7.1 and DBP 0.21+/-5.0. However, the absolute differences were significant at an individual level, with a systolic difference of 5.4+/-4.8 mmHg and a diastolic difference of 3.9 +/-3.2 mmHg. The percentages of absolute SBP/DBP differences more than 5 mmHg (21.4%/20.4%) and more than 10 mmHg (15.7%/4.7%) were considerable. The range of arm differences was clinically significant; in hypertensives, the SBP/DBP was -13.2 to +15/-9.2 to +9.6 mmHg and in nonhypertensives it was -12.9 to +15.6/-9.7 to +10.1 mmHg. CONCLUSION: Although on average there was no clinically significant relative difference between arms, absolute differences at an individual level were often clinically significant. Failure to determine interarm BP differences will lead to erroneous clinical decisions. PMID- 22781633 TI - Factors affecting continuous beat-to-beat orthostatic blood pressure response in community-dwelling older adults. AB - OBJECTIVE: To examine the effect of age, time of day, the timing of medication and food ingestion on orthostatic blood pressure response (OBP) in community dwelling adults. METHODS: A nationally representative sample of 109 community dwelling adults aged at least 50 years attended for health assessment in a pilot study of The Irish Longitudinal Study on Ageing. OBP was measured using continuous beat-to-beat plethysmography (Finometer) during active stand, and OBP with excessive artefacts were excluded. Nine outcome variables were supine systolic blood pressure (SBP), lowest standing SBP (nadir), standing SBP at 40, 60 and 120 s and the difference in supine SBP and nadir (delta SBP) and delta at 40, 60 and 120 s. Factors included for multiple linear regression analysis were age, time of assessment, interval from the last meal and whether regular medications were taken on the day. Subgroup analysis was performed on 103 respondents who were not on beta-blocker, fludrocortisone and Parkinson medications. RESULTS: There were 53 men, mean age 62.1 (SD=9.4) years. Older respondents (>=60 years) showed greater delta at 40 s by up to 12.9 mmHg. Delta SBP and delta 40, 60 and 120 were not significantly affected by the time of day or food ingestion. The effect of medications on delta 40 was no longer present in subgroup analysis. CONCLUSION: Age was the most significant determinant of OBP and was most strongly associated with greater delta at 40 s. This was independent of the time of day, food and medication ingestion. Continuous beat-to-beat plethysmography provides for a window into the pattern of OBP in community dwelling adults aged 50 years and older. PMID- 22781634 TI - Comparison of blood pressure measurements between an automated oscillometric device and a Hawksley random-zero sphygmomanometer in the northern Sweden MONICA study. AB - BACKGROUND: The Hawksley random-zero sphygmomanometer (random-zero) has been used widely in epidemiological observation studies. This study compares blood pressure measurements using the random-zero with measurements using an automated oscillometric device and suggests a correction of the automated oscillometric measurements to enable comparisons of blood pressure levels over time. METHODS: The northern Sweden MONICA population survey 2009 included 1729 participants, 853 men and 876 women, 25-74 years old. Blood pressure was measured using both random zero and an automated oscillometric device in all participants. The Omron M7 digital blood pressure monitor was used for automated oscillometric measurements. A linear mixed model was used to derive a formula to adjust the automated oscillometric readings. RESULTS: Automated oscillometric measurements of systolic blood pressure were generally lower than random-zero measurements in women [oscillometric mean 122.1 mmHg (95% confidence interval: 121.0-123.2) versus random-zero mean 124.4 mmHg (123.5-125.5)], whereas automated oscillometric measurements of systolic blood pressure were generally higher than random-zero measurements in men [oscillometric 131.1 mmHg (130.0-132.2) versus random-zero 129.0 mmHg (127.9-130.1)]. For diastolic blood pressure, automated oscillometric measurements were higher in both women [oscillometric 79.9 mmHg (79.2-80.5) versus random-zero 76.7 mmHg (76.0-77.4)] and men [oscillometric 83.1 mmHg (82.4 83.8) vs. random-zero 81.2 mmHg (80.6-81.9)]. The difference also varied with age and order of measurement. Adjustment of the automated oscillometric measurements using mixed model regression coefficients produced estimates of blood pressure that were close to the random-zero measurements. CONCLUSION: Blood pressure measurements using an automated oscillometric device differ from those with random-zero, but the oscillometric measurements can be adjusted, on the basis of sex, age and measurement order, to be similar to the random-zero measurements. PMID- 22781635 TI - Comparative study of Finapres devices. AB - BACKGROUND: Devices based on the arterial volume clamping technique, such as the Finapres, Portapres or Finometer, have become the methods of choice in studies requiring continuous noninvasive recordings of arterial blood pressure (BP). Most validation studies have used intravascular BP measurements in the radial artery as a reference. We tested the hypothesis that the simultaneous use of two Finapresses in different combinations of fingers and hands would not lead to significant differences. METHODS: Two Finapresses of the same model were used. BP was measured using four combinations of ipsilateral and contralateral middle and ring fingers and two Finapresses on 11 healthy individuals. Differences between the two devices were assessed at rest by the agreement between systolic, mean and diastolic values, pulse bandwidth, frequency response, magnitude squared coherence and drift. BP response to the Valsalva manoeuvre was used for dynamic comparisons. RESULTS: The two Finapresses showed significant differences for systolic (P=0.010), mean (P=0.008) and diastolic (P=0.021) pressures (two-way analysis of variance). No significant differences were found for drift, bandwidth or the Valsalva manoeuvre. Spectral and coherence analysis showed a linear frequency response to ~13 Hz. CONCLUSION: Different Finapres devices might show differences between the systolic, mean and diastolic BP at rest, but there is excellent agreement between dynamic indices. The response bandwidth is adequate to register the BP waveform with good accuracy, thus supporting applications in which waveform-dependent indices are extracted. Further studies are required in patients with different pathologies, including those with peripheral circulatory disorders. PMID- 22781636 TI - Synthesis and field emission properties of topological insulator Bi2Se3 nanoflake arrays. AB - High quality Bi(2)Se(3) nanoflake arrays with a large area and high-yield production have been fabricated by chemical vapor deposition. As the essential candidate for a topological insulator, the unique surface electronic states are considered to play a crucial role distinct from the bulk. Our experimental results show that environmental doping significantly affects the field emission properties of the synthesized Bi(2)Se(3) nanoflake arrays. X-ray photoelectron spectroscopy characterizations indicate that the rapid surface oxidation may prohibit the detection of the topological surface state and results in a low field emission current. This work provides another insight to investigate the surface state of topological insulator materials. PMID- 22781637 TI - Agomelatine in breast milk. PMID- 22781638 TI - [Intra-abdominal hypertension induced acute kidney injury: pressure overweigh volume]. PMID- 22781639 TI - [Left ventricular-arterial coupling in the resuscitation of refractory septic shock]. AB - OBJECTIVE: To explore the role of left ventricular-arterial coupling in the resuscitation of refractory septic shock. METHODS: A total of 58 patients with refractory septic shock admitted from January 2010 to July 2011 were retrospectively studied. Hemodynamic data, arterial lactate concentration and APACHEII (acute physiology & chronic health evaluation II) score at the beginning of and 24 hours after cardiac output monitoring, as well as the outcome of Day 28 post-diagnosis were recorded. Stroke volume index (SVI), cardiac index (CI) and global end diastolic volume index (GEDVI) were obtained through transpulmonary thermodilution technique by a pulse induced continuous cardiac output (PiCCO) system. Left ventricular end systolic volume index (LVESVI) was approximated to (GEDVI/4-SVI) while effective arterial elastance index/ventricular end systolic elastance index (EaI/EesI) was approximated to LVESVI/SVI. RESULTS: (1) APACHEII score at the 24th hour, 24 hs lactate clearance rate and 24 hs Ea/Ees variation (DeltaEa/Ees) were higher in non-survivors than those in survivors; (2) binary Logistic regression analysis showed that DeltaEa/Ees and APACHEII score at the 24th hour were the independent risk factors of mortality for refractory septic shock. And the OR value of DeltaEa/Ees was higher than that of APACHEII score (2.04 vs 1.63). Their areas of ROC curve were 0.705 (95%CI 0.569 - 0.841, P = 0.007) and 0.939 (95%CI 0.878 - 1.000, P = 0.000) respectively; (3) all hemodynamic parameters at the beginning had no difference between DeltaEa/Ees > 0 and DeltaEa/Ees <= 0 groups. CI, SVI, EGDT (early goal-directed therapy) compliance rate at the 24th hour in the DeltaEa/Ees > 0 group were lower than those in the DeltaEa/Ees <= 0 group. The effective arterial elastance index (EaI) at the 24th hour and the mortality rate of Day 28 in the DeltaEa/Ees > 0 group were higher than those in the DeltaEa/Ees <= 0 group; (4) during the 24 hs treatment, DeltaEa/Ees was correlated negatively with the variations of CI, SVI, EesI and lactate clearance rate and positively with the variations of heart rate, GEDVI, systolic vascular resistance index and EaI. CONCLUSION: DeltaEa/Ees may be used as an excellent marker of predicting the outcome of refractory septic shock. Lowing Ea/Ees in resuscitation has beneficial effects on EGDT compliance, lactate clearance and outcome. PMID- 22781640 TI - [Effect of Xuebijing injection treatment on acute respiratory distress syndrome: a multicenter prospective randomized control clinical trial]. AB - OBJECTIVE: To assess the therapeutic effect of Xuebijing injection on adult patients with acute respiratory distress syndrome (ARDS). METHODS: A multicenter prospective randomized control study was conducted at 10 intensive care units in Jiangsu province. A total of 172 early ARDS patients were randomly divided into Xuebijing treatment and control groups. All patients received routine therapy of ARDS while additional Xuebijing injection 100 ml was administered in the treatment group intravenously for 7 days. Lung injury score, acute physiology and chronic health evaluation II (APACHE II) score, multiple organ dysfunction score (MODS) and PaO2/FiO2 of the patients was recorded before and after treatment. Mortality at 28 days and the duration of mechanical ventilation were compared between two groups. RESULTS: Ninety-one patients were assigned to receive Xuebijing injection and 81 patients as control; Mortality at Days 28 and 90, the duration of mechanical ventilation and ventilation free days showed no difference between two groups (P > 0.05). PaO2/FiO2 improved after randomization versus pre treatment in all patients. There was no significant difference between two groups. Murray scores were not significantly different between two groups. In a subgroup analysis of patients with pulmonary infection, pulmonary contusion and extra-pulmonary cause, two groups had no difference in mortality at Day 28, mortality at Day 90, the duration of mechanical ventilation, ventilation free days and days of ICU stay (P > 0.05). CONCLUSION: The treatment of Xuebijing injection early in course of ARDS does not improve the mortality of ARDS patients. But it may improve lung function and oxygenation. Further studies are warranted. PMID- 22781641 TI - [Effects and mechanisms of heme oxygenase-1 on rats with postresuscitation myocardial dysfunction]. AB - OBJECTIVE: To explore the effects and mechanisms of heme oxygenase-1 on rats with postresuscitation myocardial dysfunction. METHODS: Male Sprague-Dawley rats were asphyxiated for 9 minutes and resuscitated. They were randomly divided into 4 groups: sham-operated, cardiopulmonary resuscitation (CPR), hemin and hemin + ZnPP (zinc protoporphyrin IX). Resuscitated groups had 2 observation points: 6 and 24 hours post-CPR (n = 8 for each time point). And the sham-operated group of 12 rats were divided in two observation points, according to 6 or 24 hours post operation (n = 6 each). Hemodynamic was observed. The expression of heme oxygenase-1 (HO-1) in cardiac tissue was detected by Western blot. And the activity of cardiac homogenate superoxide dismutase (SOD) was determined by xanthine oxidase method and the level of malondialdehyde (MDA) measured by the thiobarbituric acid method. Nitrotyrosine protein expression in cardiac tissue was analyzed by immunohistochemistry. RESULTS: (1) The mean blood pressure (MAP) significantly decreased in resuscitated groups after resuscitation (all P < 0.05). No difference existed between the subgroups. The scores of dP/dt40 and dP/dt significantly decreased in CPR and hemin + ZnPP groups after resuscitation (all P < 0.05). But dP/dt40 in hemin group did not differ significantly after resuscitation and -dP/dt decreased only 0.5 hour and 1 hour post-resuscitation (3341.60 +/- 524.85 and 3711.40 +/- 502.39 vs 4284.20 +/- 800.87, all P < 0.05). The scores of dP/dt40 and -dP/dt in hemin group at all time points post resuscitation were significantly higher than those in CPR and hemin + ZnPP groups (all P < 0.05). (2) Compared with the sham-operated group, the HO-1 expression, MDA level and nitrotyrosine protein expression significantly increased while the activities of SOD decreased after resuscitation in the CPR, hemin and hemin + ZnPP groups (all P < 0.05). Compared with the CPR and hemin + ZnPP groups, the expression of HO-1 and the activity of SOD increased, while MDA level and nitrotyrosine protein expression were decreased in group hemin (all P < 0.05). No difference existed in the above indices between the CPR and hemin + ZnPP groups. CONCLUSION: HO-1 can reduce myocardial oxidative stress injury after cardiopulmonary resuscitation and effectively improve post-resuscitation myocardial function in rats. PMID- 22781642 TI - [A multi-centered randomized controlled study of neo-adjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of esophagus: an interim analysis]. AB - OBJECTIVE: To evaluate the safety and validity of neo-adjuvant chemoradiotherapy followed by surgery for locally advanced esophageal carcinoma. METHODS: Patients with IIB, III staged squamous cell carcinoma of thoracic esophagus were randomly allocated to either preoperative chemoradiotherapy followed by surgery (arm A) or surgery alone (arm B). In arm A, chemotherapy and radiotherapy were performed concurrently. Patients received two cycles of vinorelbine and cisplatin. Vinorelbine at 25 mg/m(2) per day was administered as a bolus infusion at d1, d8, d22 and d29. Cisplatin at 75 mg/m(2) was administered by an intravenous infusion at d1 and d22 (or 25 mg/m(2) days 1 - 4 and 22 - 25). A total radiotherapeutic dose of 40 Gy was delivered in 20 daily fractions of 2.0 Gy each (5 d/wk for 4 weeks). Three-incisioned esophagectomy was performed at Weeks 4 - 6 after chemoradiotherapy. Primary outcome was overall survival time. An interim analysis was performed in June 2011. RESULTS: From July 2007 to June 2011, 123 eligible patients were randomly assigned at 7 cooperative cancer centers (54 cases in arm A vs 69 cases in arm B). In arm A, the clinical response rate of chemoradiotherapy was 90.7%. All patients finished the preoperative chemoradiotherapy. Forty-nine cases continued to receive esophagectomy. The pathological complete response rate was 29.6%. The rate of R0 resection in arm A was significant higher than that in arm B(96.0% vs 85.5%, P = 0.015). The most common grade 3/4 toxicity of chemoradiotherapy was leukopenia occurring in 33 cases (61.1%). Vomiting and esophagitis were usually of Grade 1/2. No patient died or abandoned surgery because of chemoradiation toxicity. Between arms A and B, operative duration, blood loss, duration of chest tube drainage and length of postsurgical hospital stay were similar. The incidences of postoperative heart failure (2.0% vs 1.4%, P = 1.000), anastomotic leakage (8.2% vs 11.6%, P = 0.759) and hoarseness (6.1% vs 4.3%, P = 0.691) were not significantly different. The incidence of pulmonary infection in arm A was slightly higher than that in arm B (8.2% vs 1.4%, P = 0.094). No perioperative deaths occurred in either group. There were no significant differences in overall survivals at 1, 2 years between arms A and B (85.6%/75.5% vs 79.1%/66.1%, P = 0.207). The disease-free survivals at 1, 2 years in arm A were slightly higher than in arm B (86.6%/83.2% vs 70.9%/61.8%, P = 0.075). CONCLUSION: Neo-adjuvant chemoradiation followed by surgery may achieve a high clinical response rate and pathologic complete tumor regression rate. It significantly increases the R0 resection rate and down stage the esophageal cancer patients. But its ultimate efficacy awaits further follow up studies. PMID- 22781643 TI - [Impulsive decision-making behaviors in heroin addicts: a study of functional magnetic resonance imaging]. AB - OBJECTIVE: To explore the brain regions associated with impulsive decision-making behaviors and interpret the nervous mechanism for addiction and relapse in heroin abusers. METHODS: Using the paradigms of psychological experiment, the subjects in both heroin addiction group (HA group) and normal control group (HC group) performed Iowa gambling task (IGT) and simultaneously underwent functional magnetic resonance imaging (fMRI) scan. All the above data were gathered and then analyzed by SPM5 software to explore both the brain regions and their functional changes correlated with impulsive decision-making. RESULTS: Evidence by IGT behavioral consequences demonstrated that the net scores in HC group increased with numbers of decision-making whereas no increment (fluctuating between-1 and 0) was observed in HA group. Based on the results of fMRI analysis, right orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), left ventromedial prefrontal cortex (MPFC) and anterior cingulate cortex (ACC) were activated in both groups. But the right OFC was more active while the right DLPFC and left MPFC were weaker in HA group versus the HC group. Meanwhile, activation of right lenticular nucleus, right thalamus, right insula, hippocampus and left caudate nucleus were observed in HA group. CONCLUSION: Heroin abusers are incapable of impulsive decision-making in behavioral studies. Such a brain region as prefrontal cortex participates in the decision-making performance and control of impulsiveness. Functionally abnormal brain regions correlated with impulsive decision-making may be one cause of genesis, maintenance and relapse of heroin addiction. PMID- 22781644 TI - [Surgical techniques and efficacies of deep brain stimulation in the treatment of essential tremor]. AB - OBJECTIVE: To explore the surgical techniques and efficacies of deep brain stimulation (DBS) in the treatment of the patients with essential tremor (ET). METHODS: A total of 6 ET patients from January 2004 to June 2011 at Department of Neurosurgery, Beijing Tiantan Hospital were recruited to receive DBS at ventral intermediate nucleus of thalamus (Vim-DBS) (n = 5) and subthalamic nucleus (STN DBS) (n = 1). All underwent stereotactically guided DBS procedures utilizing atlas of neuroanatomy and neurophysiology, pre-operative magnetic resonance imaging (MRI), microelectrode recording and intra-operative testing for target locating. Postoperative computed tomography (CT) and/or MRI scan were performed after implantation. Such stimulation parameters as stimulus voltage, frequency, pulse width and polarity configuration were adjusted postoperatively to optimize tremor control and maximize battery life. The patients were followed by further consultations or telephone for a comprehensive evaluation of their therapeutic efficacies. RESULTS: All patients showed typical electrical signal and relief of tremor symptoms with significant tremor control. No severe adverse events, such as infection, hemorrhage, paresthesia, dysarthria, cognitive deficits, imbalance and diplopia, appeared after the implantation of DBS electrodes. CONCLUSION: Vim DBS and STN-DBS are both safe and effective for the controls of unilateral and bilateral tremors. PMID- 22781645 TI - [Rapid pore cranial drilling and ventricular drainage in the treatment of ventricular hemorrhage caused by thalamic hemorrhage: an analysis of 401 cases]. AB - OBJECTIVE: To summarize the clinical efficacies and experiences of using rapid pore cranial drilling and external ventricular drainage (EVD) in the treatment of ventricular hemorrhage caused by thalamic hemorrhage. METHODS: Retrospective analysis was conducted for 401 patients at 5 hospitals from May 1983 to December 2010. They underwent EVD with an infusion of urokinase for intraventricular hemorrhage caused by thalamic hemorrhage. There were 212 males and 189 females with an age range of 19 - 78 years. RESULTS: After a 1-month therapy, the outcomes were cure 147/401 (36.7%), improvement 192/401 (47.9%) and others (death and against-advice discharge) 62/401 (15.4%). After 1-3-month treatment, their prognoses were evaluated by activity of daily living (ADL): ADLI 147/401, ADLII 82/401, ADLIII 76/401, ADLIV 19/401, ADLV 15/401, death 43/401 and against-advice discharge 19/401. During a follow-up period of 1 - 3 years, 274 patients showed the following outcomes: ADLI 122/243, ADLII 63/243, ADLIII 58/243 while 31 patients died from pulmonary infection. CONCLUSION: The procedure of EVD (including an infusion of urokinase) with rapid pore cranial drilling is preferred treatment for ventricular hemorrhage caused by thalamic hemorrhage. PMID- 22781646 TI - [Clinical effect of ultrasound combined with anatomy-measure guidance botulinum toxin type A injection in poststroke patients with spasticity]. AB - OBJECTIVE: To evaluate the clinical efficacies of botulinum toxin type A (BTX-A) injection under ultrasonic guidance and body surface positioning in poststroke patients with lower extremities spasticity. METHODS: From January 2009 to January 2011, a total of 18 patients with stroke-related spasticity in lower extremities were recruited at Third Affiliated Hospital of Sun Yat-sen University. Under the guide of color Doppler ultrasound and body surface positioning, BTX-A was injected into multi-points of muscles. The outcome after BTX-A injection was assessed by modified Ashworth scale (MAS), passive range of movement (PROM), 10 meter walking test (10 MWT) and Berg balance scale (BBS). Assessments were performed at baseline, Day 3, Weeks 1, 2, 4 and 12 post-injection respectively. RESULTS: Compared the scores of MAS (MAS(pre-treatment) 2.6 +/- 0.5, MAS(post treatment) 1.9 +/- 0.2 - 1.1 +/- 0.3 score), PROM (PROM(pre-treatment) 7.2 +/- 2.4 degrees , PROM(post-treatment) 12.3 +/- 2.0 - 18.6 +/- 2.2 degrees ) between baseline and follow-up at Weeks 1, 2, 4 and 12 post-treatment, there were significant statistical differences (P < 0.05).10 MW (10 MWT(pre-treatment) 55.1 +/- 5.2 s, 10 MWT(post-treatment) 48.6 +/- 4.2 - 42.9 +/- 3.8 s) and BBS (BBS(pre treatment) 34.7 +/- 5.1, BBS(post-treatment) 39.9 +/- 4.9 - 45.8 +/- 2.1 score) improved greatly at Weeks 2, 4 and 12 post-treatment. CONCLUSION: Ultrasonic guidance and body surface positioning is an accurate positioning modality of using BTX-A for treating the spasticity of lower extremities. PMID- 22781647 TI - [Atypical polypoid adenomyoma of the uterus: an analysis of 17 cases]. AB - OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment of Atypical Polypoid Adenomyoma of the uterus (APA). METHODS: A retrospective study was made of 17 patients with APA, who were hospitalized at Peking Union Medical College Hospital from 2003 to 2010. Those patients' clinical characteristics, diagnosis, and treatments are analyzed respectively. The patients ranged from 19 to 53 (median 39) years old, Most of them (15/17) are during child-bearing period. There was one patient with infertility, two of the patients were postmenopausal. RESULTS: Fourteen cases had irregular vaginal bleeding clinically. Most of the pathology were polypous, which is more than 1 cm. Fifteen cases were characteristically polypoid, among which there were one case with multi polypoid and one case was extensive. Eight cases were located in the uterine cavity. Six cases were located in the lower uterine segment. Three cases were located in cervix. None of the cases were diagnosed, while all of them were diagnosed by pathology after primary surgical. Fifteen patients had polypectomy (among them, five patients took drug therapy after the surgical), while the remaining two patients had hysterectomy. Two of the five patients, who took drug therapy, were pregnant. One patient was deteriorated with carcinoma of endometrium. CONCLUSION: Although most cases of APA were benign, a few cases were associated with low malignant potential of recurrence. The treatment should depend on the age and reproductive desire of patient. And long-term follow-up is suggested. PMID- 22781648 TI - [Parturition approach of iatrogenic preterm infants]. AB - OBJECTIVE: To explore the relatively safe parturition approach of iatrogenic preterm infants. METHODS: Methods analysis the result of 185 cases Iatrogenic preterm infants come in our hospital from Feb. 2007-Jan. 2011, divided into two groups by different parturition way: c-section group and vaginal delivery group, to compare the influence of iatrogenic preterm infants delivered by different parturition way. RESULTS: The c-section group premature infant complication (34.1%, 42/123) and the mortality rate (9.7%, 12/123) reduces obviously compared to the vaginal delivery group (P < 0.05), especially grave asphyxia and intracranial hemorrhage (P < 0.01). CONCLUSION: In inevitable iatrogenic preterm labor, cesarean section may markedly reduce the complications and mortality rate of preterm infants. PMID- 22781649 TI - [Fabrication of tissue engineered vein containing valve scaffolds]. AB - OBJECTIVE: To fabricate porous biodegradable tissue engineered vein containing valve scaffolds. METHODS: Based on the self-made cast, the tissue engineered vein containing valve scaffolds was fabricated by injection molding plus thermally induced phase separation. Poly (lactic-co-glycolic acid) (PLGA, LA/GA mole ratio 75:25) was used as matrices. Morphological structures and biocompatibility of scaffolds were tested. Cell seeding on scaffold was performed and the mechanic characteristics of cellular constructs evaluated. RESULTS: The scaffold had an inner diameter of 9 mm with a wall thickness of 0.9 mm and the thickness of valves was (0.32 +/- 0.04) mm. Scanning electron microscopic (SEM) micrographs showed regular ladder-like porous structures and the average pore size and porosity of scaffolds were 10 - 20 um and 90%. The PLGA scaffolds were biocompatible. The cellular constructs were tested in vitro, and the valve leaflets were functionally capable of opening and closing when stimulated. CONCLUSION: Based on the self-made cast, the tissue engineered vein containing valve scaffolds can be fabricated by injection molding plus thermally induced phase separation. Further researches are warranted. PMID- 22781650 TI - [Observation of neuropeptides in bladder after spinal cord injury in rats]. AB - OBJECTIVE: To observe the altered expressions of neuropeptide Y, substance P and vasoactive intestinal peptide in detrusor of SD rats after spinal cord injury and explore the relationship of the above neuropeptides and neurogenic bladder after spine cord injury. METHODS: Twenty male clean-grade SD rats, aged 6 weeks, were selected and randomized into spinal cord injury group (n = 10) and control group (n = 10). Rats in spinal cord injury group were smashed at T10 to cause spinal cord incomplete injury model by the weight drop method while laminectomy alone without smashing was administered in control group. At Week 1 post-operation, all rats were assessed by the maximum bladder capacity, bladder compliance and detrusor pressure for the confirmation of spastic bladder. And all detrusor specimens were marked with argentation and immunohistochemistry for the analyses of nerve fibers, neuropeptide Y, substance P and vasoactive intestinal peptide. The results were evaluated with semiquantitative method to observe the contents of nerve fiber and neuropeptides. RESULTS: At Week 1 post-operation, the mean maximum bladder compactly, mean maximum detrusor pressure and mean compliance in SCI rats was 0.71 +/- 0.24 ml, 32.27 +/- 3.12 cm H2O and 0.020 +/- 0.009 ml/cm H2O versus 2.0 +/- 0.4 ml, 21.0 +/- 3.0 cm H2O and 0.090 +/- 0.020 ml/cm H2O in normal control group respectively. And the differences were statistically significant (P < 0.01). Meanwhile, the mean content of nerve fibers of neurogenic bladder decreased markedly than that of normal control group (2.58 +/- 0.13 vs 5.65 +/- 0.26). As compared with the normal control group, the expressions of neuropeptide Y, substance P and vasoactive intestinal peptide (mean integrated optical density: 3.2 +/- 0.5, 1.7 +/- 0.4 and 2.1 +/- 0.4 respectively) decreased dramatically in SCI rats. And the differences were statistically significant (P < 0.01). CONCLUSION: The number of nerve fibers and the content of neuropeptides significantly decrease in neurogenic bladder after spinal cord injury in rats. The reduction of neuropeptides may be correlated with the formation of neurogenic bladder after spinal cord injury. PMID- 22781651 TI - [Study of the correlation about IGF-I receptor and beta-amyloid in Alzheimer's disease]. AB - OBJECTIVE: To detect the expression of IGF-I receptor in the hippocampus neuron of rat treated by Abeta(1-42), and thus from the receptor level explore the disorder of central nervous insulin signaling and the possible molecular mechanism of Alzheimer disease. METHODS: Cultured primary hippocampus neurons were treated with different concentrations of Abeta(1-42), apoptosis rate was detected by flow cytometry, real-time quantitative PCR and Western blot were used to detect IGF-I receptor expression. RESULTS: Primary cultured cells mature in 7(th) days; after detected by flow cytometry, early apoptosis rate in Abeta(1-42) 0, 30, 60, 100 umol/L groups showed a concentration-dependent increase. PCR results showed that, in 30 (1.72 +/- 0.33) and 60 umol/L (1.86 +/- 0.36) treatment groups levels of the IGF-I receptor gene were significantly higher than the control group (regarded as 1) (P < 0.01), 100 umol/L group (0.70 +/- 0.15) was significantly lower than the control group (P < 0.05). Results of Western blot showed 30 and 60 umol/L protein level of the treatment groups are 1.08 +/- 0.04, 1.74 +/- 0.08 (P < 0.01) and 100 umol/L group was 0.79 +/- 0.11(P < 0.05), which had same trend with PCR. CONCLUSIONS: Abeta(1-42) induced altered expression of IGF-I receptors in rat hippocampus cells, maybe one of the molecule mechanisms of Alzheimer disease. PMID- 22781652 TI - [An experimental study on catheterization in rat's hepatic artery and interventional therapy through carotid artery]. AB - OBJECTIVE: To investigate the feasibility and safety of catheterization in rat hepatic artery and interventional therapy through carotid artery. METHODS: A total of 30 Sprague-Dawley rats were randomly divided into 2 groups. All were punctured through left common carotid artery (LCCA) under intraperitoneal injection anesthesia. Microcatheter was inserted through a puncturing outer cannula into celiac artery and angiography performed to investigated the anatomical structure. Then a microcatheter was inserted into proper hepatic artery. One group was perfused with epirubicin 5 mg while another embolized with lipidol and polyvinyl (PVA). The status of vascular patency was re-examined by celiac angiography after perfusion and embolization. The 2-week survival rate (SR) and related complications were observed. RESULTS: Except for one failed case, all other cases were successfully inserted and celiac-gastroduodenal arteriography was completed with a success rate of 97% (29/30). The anastomosis between gastroduodenal artery (GDA) and superior mesenteric artery (SMA) was demonstrated in 28 cases (28/29, 96.6%). In 14 cases with perfusion therapy, arteriography demonstrated all branches of celiac artery had no occlusion while 10 embolized cases (10/15, 67%) had the main branch occlusion of gastroduodenal artery and 5 (5/15, 33%) stayed open. No postoperative abnormality was found in the limb motor function. Five had the drooping of left upper eyelid during 12 - 24 h after intervention and subsided after a week. And 10 embolized via main branch of gastroduodenal artery showed a poor appetite within 3 days postoperation and recovered gradually after 3 days. After intervention, 27 rats survived in 2 weeks. The survival rate was 93% (27/29). One died of incision infection and another neck hematoma. CONCLUSION: Catheterization in hepatic artery and interventional therapy through carotid artery is both feasible and safe. It may have a high application value. PMID- 22781653 TI - [Atropine treatment of hypoxic bradycardia accelerated the occurrence of cardiac arrest]. AB - OBJECTIVE: To explore the therapeutic effects of atropine for hypoxic bradycardia during the occurrence of cardiac arrest. METHODS: Sixty-four adult New Zealand rabbits were selected and allocated randomly into 2 groups: instant resuscitation group and 8-minute resuscitation group. Each animal was anesthetized by an intravenous injection of sodium pentobarbital and intubated through tracheostomy. The tracheostomy tube was then clamped off to induce acute hypoxia. At soon as heart rate (HR) decreased to a half of basic-heart-rate, either atropine 50 ug/kg or 0.9% normal saline as control was randomly administered intravenously. In instant resuscitation group (group T1), the tracheostomy tube was unclamped and cardiopulmonary resuscitation (CPR) initiated for the occurrence of cardiac arrest (MAP < 10 mm Hg). In 8-minute resuscitation group (group T2), the tracheostomy tube was clamped for 8 minutes and then CPR initiated. The statistical data were analyzed by SPSS 10.0. All data were reported as x(-) +/- s. T test was used to compare the means of cardiac arrest time between two groups, one-way ANONA to compare HR & mean arterial pressure (MAP) and Fisher's exact probabilities test to compare the survival rates between two groups. A value of P < 0.05 was considered statistically significant. RESULTS: The heart rate of atropine treated group was higher than that of normal saline group for about 90 minutes post-dosing. In atropine group, the MAP decrease was significantly faster than that of normal saline group (P < 0.01). Most importantly, after the clamping of tracheostomy tube, the average time of cardiac arrest occurred at (335.43 +/- 43.25) s in atropine group versus (371 +/- 55) s in normal saline group (P = 0.006). CONCLUSION: Although atropine treatment of severe hypoxic bradycardia improves the decrease of HR for a short time, it decreases MAP and accelerates the occurrence of cardiac arrest result from acute hypoxia. But the mortality rate is not improved by the treatment of atropine. PMID- 22781654 TI - RETRACTED: S-allyl cysteine protects against 6-hydroxydopamine-induced neurotoxicity in the rat striatum: involvement of Nrf2 transcription factor activation and modulation of signaling kinase cascades. AB - Pharmacological activation at the basal ganglia of the transcription factor Nrf2, guardian of redox homeostasis, holds a strong promise for the slow progression of Parkinson's disease (PD). However, a potent Nrf2 activator in the brain still must be found. In this study, we have investigated the potential use of the antioxidant compound S-allyl cysteine (SAC) in the activation of Nrf2 in 6 hydoxydopamine (6-OHDA)-intoxicated rats. In the rat striatum, SAC by itself promoted the Nrf2 dissociation of Keap-1, its nuclear translocation, the subsequent association with small MafK protein, and further binding of the Nrf2/MafK complex to ARE sequence, as well as the up-regulation of Nrf2-dependent genes encoding the antioxidant enzymes HO-1, NQO-1, GR, and SOD-1. In vivo and in vitro experiments to identify signaling pathways activated by SAC pointed to Akt as the most likely kinase participating in Nrf2 activation by SAC. In PC12 cells, SAC stimulated the activation of Akt and ERK1/2 and inhibited JNK1/2/3 activation. In the rat striatum, the SAC-induced activation of Nrf2 is likely to contribute to inhibit the toxic effects of 6-OHDA evidenced by phase 2 antioxidant enzymes up-regulation, glutathione recovery, and attenuation of reactive oxygen species (ROS), nitric oxide (NO), and lipid peroxides formation. These early protective effects correlated with the long-term preservation of the cellular redox status, the striatal dopamine (DA) and tyrosine hydroxylase (TH) levels, and the improvement of motor skills. Therefore, this study indicates that, in addition to direct scavenging actions, the activation of Nrf2 by SAC might confer neuroprotective responses through the modulation of kinase signaling pathways in rodent models of PD, and suggests that this antioxidant molecule may have a therapeutic value in this human pathology. PMID- 22781656 TI - Core-extended rylene dyes via thiophene annulation. AB - Annulation of thiophenes directly into the bay regions of rylene dyes through effective Stille coupling and subsequent ring-fusion under Scholl conditions leads to core-extended rylene tetracarboxylic diimides with interesting electro optical properties. PMID- 22781655 TI - Deficiency of alphaB crystallin augments ER stress-induced apoptosis by enhancing mitochondrial dysfunction. AB - Endoplasmic reticulum (ER) stress is linked to several pathological conditions including age-related macular degeneration. Excessive ER stress initiates cell death cascades which are mediated, in part, through mitochondrial dysfunction. Here, we identify alphaB crystallin as an important regulator of ER stress induced cell death. Retinal pigment epithelial (RPE) cells from alphaB crystallin (-/-) mice, and human RPE cells transfected with alphaB crystallin siRNA, are more vulnerable to ER stress induced by tunicamycin. ER stress-mediated cell death is associated with increased levels of reactive oxygen species, depletion of glutathione in mitochondria, decreased superoxide dismutase activity, increased release of cytochrome c, and activation of caspases 3 and 4. The ER stress signaling inhibitors, salubrinal and 4-(2-aminoethyl) benzenesulfonyl fluoride, decrease mitochondrial damage and reduce RPE apoptosis induced by ER stress. Prolonged ER stress decreases levels of alphaB crystallin, thus exacerbating mitochondrial dysfunction. Overexpression of alphaB crystallin protects RPE cells from ER stress-induced apoptosis by attenuating increases in Bax, CHOP, mitochondrial permeability transition, and cleaved caspase 3. Thus, these data collectively demonstrate that alphaB crystallin provides critical protection of mitochondrial function during ER stress-induced RPE apoptosis. PMID- 22781658 TI - Malignant lymphoma with diffuse cardiac involvement detected by multiple imaging examinations: a case report. AB - INTRODUCTION: In malignant lymphoma, cardiac involvement, which usually forms pathologically focal and firm nodules in the cardiac walls, is considered to be a late manifestation of the disease. CASE PRESENTATION: We describe the case of a 71-year-old Asian Japanese woman whose first presentation of lymphoma was congestive heart failure. Multiple imaging examinations and laboratory findings led to a presumed diagnosis of a malignant lymphoma. A tissue diagnosis of the mediastinal mass could not be performed due to our patient's generally poor condition. Our patient received corticosteroid therapy, but died 42 days after her admission. An autopsy revealed lymphoid cells encircling her ventricular wall and infiltrating her endocardium. A histological examination confirmed the diagnosis of diffuse large B-cell lymphoma. CONCLUSION: Imaging examinations such as echocardiography, computed tomography with three-dimensional reconstruction, and gallium-67-citrate scintigraphy could clearly detect the diffuse cardiac involvement antemortem. A combination of these imaging techniques could provide a working diagnosis and allow empirical initiation of treatment in patients with poor general condition. PMID- 22781659 TI - Recasting cancer trials. PMID- 22781657 TI - Sex, hormones, and stress: how they impact development and function of the carotid bodies and related reflexes. AB - Progesterone and corticosterone are key modulators of the respiratory control system. While progesterone is widely recognized as an important respiratory stimulant in adult and newborn animals, much remains to be described regarding the underlying mechanisms. We review the potential implication of nuclear and membrane progesterone receptors in adults and in newborns. This raises intriguing questions regarding the contribution of progesterone as a protective factor against some respiratory control disorders during early life. We then discuss our current understanding of the central integration of stressful stimuli and the responses they elicit. The fact that this system interacts with the respiratory control system, either because both share some common neural pathways in the brainstem and hypothalamus, or because corticosterone directly modulates the function of the respiratory control network, is a fascinating field of research that has emerged over the past few years. Finally, we review the short- and long term consequences of disruption of stress circuitry during postnatal development on these systems. PMID- 22781660 TI - Swiss hope for phoenix from Merck Serono's ashes. PMID- 22781662 TI - NCATS launches drug repurposing program. PMID- 22781665 TI - Coalition aims to accelerate translation of cell therapies. PMID- 22781668 TI - First FDA-approved beta-amyloid diagnostic hits the market. PMID- 22781670 TI - Obama administration report underlines support for biotech. PMID- 22781671 TI - Debate over details of US biosimilar pathway continues to rage. PMID- 22781672 TI - Beyond counting tumor cells. PMID- 22781673 TI - Reading cancer's blueprint. PMID- 22781674 TI - From academic solos to industrial symphonies. PMID- 22781675 TI - Gene therapy matures in the clinic. PMID- 22781676 TI - TAL effector RVD specificities and efficiencies. PMID- 22781677 TI - Incorporating biomarkers into clinical trial designs: points to consider. PMID- 22781678 TI - The Multiple Myeloma Research Foundation's evolving focus on drug R&D. PMID- 22781679 TI - The challenges posed by cancer heterogeneity. PMID- 22781680 TI - T-cell therapy at the threshold. PMID- 22781681 TI - Antibody specification beyond the target: claiming a later-generation therapeutic antibody by its target epitope. PMID- 22781683 TI - ABSOLUTE cancer genomics. PMID- 22781684 TI - New lysine methyltransferase drug targets in cancer. PMID- 22781685 TI - The sweet allure of XNA. PMID- 22781691 TI - Compressive genomics. PMID- 22781692 TI - The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. AB - Progress has been made recently in developing antibody-drug conjugates (ADCs) that can selectively deliver cancer drugs to tumor cells. In principle, the idea is simple: by attaching drugs to tumor-seeking antibodies, target cells will be killed and nontarget cells will be spared. In practice, many parameters needed to be addressed to develop safe and effective ADCs, including the expression profiles of tumor versus normal tissues, the potency of the drug, the linker attaching the drug and placement of the drug on the antibody, and the pharmacokinetic and stability profiles of the resulting ADC. All these issues had been taken into account in developing brentuximab vedotin (Adcetris), an ADC that recently received accelerated approval by the US Food and Drug Administration for the treatment of relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL). Research is under way to extend the applications of brentuximab vedotin and to advance the field by developing other ADCs with new linker and conjugation strategies. PMID- 22781693 TI - From single cells to deep phenotypes in cancer. AB - In recent years, major advances in single-cell measurement systems have included the introduction of high-throughput versions of traditional flow cytometry that are now capable of measuring intracellular network activity, the emergence of isotope labels that can enable the tracking of a greater variety of cell markers and the development of super-resolution microscopy techniques that allow measurement of RNA expression in single living cells. These technologies will facilitate our capacity to catalog and bring order to the inherent diversity present in cancer cell populations. Alongside these developments, new computational approaches that mine deep data sets are facilitating the visualization of the shape of the data and enabling the extraction of meaningful outputs. These applications have the potential to reveal new insights into cancer biology at the intersections of stem cell function, tumor-initiating cells and multilineage tumor development. In the clinic, they may also prove important not only in the development of new diagnostic modalities but also in understanding how the emergence of tumor cell clones harboring different sets of mutations predispose patients to relapse or disease progression. PMID- 22781694 TI - Modeling and predicting clinical efficacy for drugs targeting the tumor milieu. AB - Disappointing results from most late-stage clinical trials of cancer therapeutics indicate a need for improved and more-predictive animal tumor models. This insufficiency of models, combined with the advent of a class of drugs that target the tumor microenvironment rather than the tumor cell, presents new challenges for designing and interpreting preclinical efficacy studies. A comparison of the clinical efficacy of anti-angiogenic drugs with their corresponding preclinical studies over the past two decades offers many lessons that can inform and improve the design of experiments in existing mouse models. In addition, technological and logistical advances in mouse models of human cancer over the past five years have the potential to increase the clinical translatability of animal studies. PMID- 22781695 TI - Oncolytic virotherapy. AB - Oncolytic virotherapy is an emerging treatment modality that uses replication competent viruses to destroy cancers. Recent advances include preclinical proof of feasibility for a single-shot virotherapy cure, identification of drugs that accelerate intratumoral virus propagation, strategies to maximize the immunotherapeutic action of oncolytic viruses and clinical confirmation of a critical viremic threshold for vascular delivery and intratumoral virus replication. The primary clinical milestone has been completion of accrual in a phase 3 trial of intratumoral herpes simplex virus therapy using talimogene laherparepvec for metastatic melanoma. Key challenges for the field are to select 'winners' from a burgeoning number of oncolytic platforms and engineered derivatives, to transiently suppress but then unleash the power of the immune system to maximize both virus spread and anticancer immunity, to develop more meaningful preclinical virotherapy models and to manufacture viruses with orders of-magnitude higher yields than is currently possible. PMID- 22781698 TI - Managing knowledge-intensive workers. PMID- 22781696 TI - Therapeutic targets in cancer cell metabolism and autophagy. AB - The metabolism of cancer cells is reprogrammed both by oncogene signaling and by dysregulation of metabolic enzymes. The resulting altered metabolism supports cellular proliferation and survival but leaves cancer cells dependent on a continuous supply of nutrients. Thus, many metabolic enzymes have become targets for new cancer therapies. Recently, two processes-expression of specific isoforms of metabolic enzymes and autophagy-have been shown to be crucial for the adaptation of tumor cells to changes in nutrient availability. An increasing number of approved and experimental therapeutics target these two processes. A better understanding of the molecular basis of cancer-associated metabolic changes may lead to improved cancer therapies. PMID- 22781697 TI - Combinatorial drug therapy for cancer in the post-genomic era. AB - Over the past decade, whole genome sequencing and other 'omics' technologies have defined pathogenic driver mutations to which tumor cells are addicted. Such addictions, synthetic lethalities and other tumor vulnerabilities have yielded novel targets for a new generation of cancer drugs to treat discrete, genetically defined patient subgroups. This personalized cancer medicine strategy could eventually replace the conventional one-size-fits-all cytotoxic chemotherapy approach. However, the extraordinary intratumor genetic heterogeneity in cancers revealed by deep sequencing explains why de novo and acquired resistance arise with molecularly targeted drugs and cytotoxic chemotherapy, limiting their utility. One solution to the enduring challenge of polygenic cancer drug resistance is rational combinatorial targeted therapy. PMID- 22781701 TI - Isolation of rat portal fibroblasts by in situ liver perfusion. AB - Liver fibrosis is defined by the excessive deposition of extracellular matrix by activated myofibroblasts. There are multiple precursors of hepatic myofibroblasts, including hepatic stellate cells, portal fibroblasts and bone marrow derived fibroblasts. Hepatic stellate cells have been the best studied, but portal fibroblasts are increasingly recognized as important contributors to the myofibroblast pool, particularly in biliary fibrosis. Portal fibroblasts undergo proliferation in response to biliary epithelial injury, potentially playing a key role in the early stages of biliary scarring. A method of isolating portal fibroblasts would allow in vitro study of this cell population and lead to greater understanding of the role portal fibroblasts play in biliary fibrosis. Portal fibroblasts have been isolated using various techniques including outgrowth and liver perfusion with enzymatic digestion followed by size selection. The advantage of the digestion and size selection technique compared to the outgrowth technique is that cells can be studied without the necessity of passage in culture. Here, we describe a modified version of the original technique described by Kruglov and Dranoff for isolation of portal fibroblasts from rat liver that results in a relatively pure population of primary cells. PMID- 22781702 TI - pH-triggered blooming of 'nano-flowers' for tumor intracellular drug delivery. AB - With the decrease in pH value, the 'nano-flower' exhibited a half-open state to expose the target ligands on the surface under tumor acidic conditions and fully bloomed to release Dox under endosomal acidic conditions. PMID- 22781703 TI - Linking the Tinnitus Questionnaire and the subjective Clinical Global Impression: which differences are clinically important? AB - BACKGROUND: Development of new tinnitus treatments requires prospective placebo controlled randomized trials to prove their efficacy. The Tinnitus Questionnaire (TQ) is a validated and commonly used instrument for assessment of tinnitus severity and has been used in many clinical studies. Defining the Minimal Clinically Important Difference (MCID) for TQ changes is an important step to a better interpretation of the clinical relevance of changes observed in clinical trials. In this study we aimed to estimate the minimum change of the TQ score that could be considered clinically relevant. METHODS: 757 patients with chronic tinnitus were pooled from the TRI database and the RESET study. An anchor-based approach using the Clinical Global Impression (CGI) scale and distributional approaches were used to estimate MCID. Receiver Operating Characteristic (ROC) curves were calculated to define optimal TQ change cutoffs discriminating between minimally changed and unchanged subjects. RESULTS: The relationship between TQ change scores and CGI ratings of change was good (r = 0.52, p < 0.05). Mean change scores associated with minimally better and minimally worse CGI categories were -6.65 and +2.72 respectively. According to the ROC method MCID for improvement was -5 points and for deterioration +1 points. CONCLUSION: Distribution and anchor-based methods yielded comparable results in identifying MCIDs. DeltaTQ scores of -5 and +1 points were identified as the minimal clinically relevant change for improvement and worsening respectively. The asymmetry of the MCIDs for improvement and worsening may be related to expectation effects. PMID- 22781704 TI - New quinoline-5,8-dione and hydroxynaphthoquinone derivatives inhibit a chloroquine resistant Plasmodium falciparum strain. AB - We report on the design, synthesis, and in vitro evaluation of new quinoline-5,8 dione and hydroxynaphthoquinone derivatives. The synthesized compounds were evaluated for in vitro antimalarial activity against Plasmodium falciparum. Of the 15 compounds, 7a-c, 8a, 9b, 11, and 15 were effective in growth inhibition with IC(50) values of below 5 MUM. PMID- 22781705 TI - Evaluation of 4 new generation portable ventilators. AB - BACKGROUND: Portable ventilators are increasingly utilized in the intra- and inter-hospital transport of patients. We evaluated 4 portable ventilators, Impact EMV, CareFusion LTV 1200, Newport HT70, and Hamilton T1, in terms of triggering, delivered tidal volume (V(T)) accuracy, battery duration, delivered F(IO(2)) accuracy, and gas consumption. METHODS: Triggering was tested using a microprocessor controlled breathing simulator that simulated a weak, normal, and aggressive inspiratory effort using muscle pressures of -2, -4, and -8 cm H2O respectively. Delivered V(T) and F(IO(2)) accuracy were evaluated across a range of operation. To determine gas consumption, the ventilators were attached to an E type oxygen cylinder and operated at an F(IO(2)) of 1.0 until the tank was depleted. Battery duration was tested by operating each ventilator at an F(IO(2)) of 0.21 until the device ceased to operate. RESULTS: Differences remain among devices in several aspects of the testing protocol. Gas consumption ranged from 9.2 to 16 L/min. Battery duration ranged from 101 to 640 min. Triggering performance varied among devices but was consistent breath to breath within the same device, using the fastest and slowest rise time settings. F(IO(2)) accuracy varied at the low range on the 50 mL V(T) setting with one device, and at the high range on both the 50 mL and 500 mL V(T) settings with another. CONCLUSIONS: Manufacturers continue to improve the performance of portable ventilators. All the ventilators we tested performed well on V(T) delivery across a range of settings, using both the internal drive mechanism (F(IO(2)) 0.21) and compressed oxygen (F(IO(2)) 1.0). Two of the ventilators were unable to deliver accurate F(IO(2)) across the range of V(T). None of the devices was clearly superior to the others in all aspects of our evaluation. PMID- 22781706 TI - Hepatoprotective and anti-inflammatory effects of silibinin on experimental preeclampsia induced by L-NAME in rats. AB - AIMS: Inhibition of nitric oxide synthase with N-omega-nitro-l-arginine methyl ester (l-NAME) has been employed as an experimental model of human preeclampsia. This study determined the protective effect of silibinin, a flavonoid with anti inflammatory and hepatoprotective properties on the deleterious effects observed in experimentally induced preeclampsia in rats. MAIN METHODS: Pregnant Wistar rats were treated during gestation (days 10-20) with l-NAME (70-80mg/kg/day) in drinking water or with l-NAME plus silibinin (100mg/kg/day, orally) starting at day 0, day 7 or day 14 of pregnancy. Systolic blood pressure was recorded from gestation days 0 to 21. A control group of pregnant non-treated rats was analyzed similarly. On day 21 the rats were euthanized and the following parameters were evaluated: proteinuria, platelet count, liver histopathology and reproductive outcome. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1beta), IL-6, IL-10 and interferon-gamma (IFN-gamma) were determined in liver homogenate by enzyme immunoassay. KEY FINDINGS: In comparison with the l-NAME group the silibinin treatment reduced the values of systolic blood pressure, proteinuria, TNF-alpha, IL-1beta and IFN-gamma in liver, normalized the platelet count and improved fetal outcomes. Histopathological lesions in liver of the l-NAME group showed intense mononuclear inflammatory infiltrate and thickening of muscle tunica of arterial vessel, mainly in the periportal area. Silibinin treatment induced attenuation of periportal inflammatory infiltrate, showing an association between inflammatory infiltrate and TNF-alpha, IL-1beta and IFN-gamma levels in liver homogenate. SIGNIFICANCE: Silibinin administration to l-NAME-treated rats displays anti-inflammatory and immunomodulatory actions that may contribute to its hepatoprotective effects and improve reproductive outcomes in experimental preeclampsia. PMID- 22781707 TI - Indoxyl sulfate enhances angiotensin II signaling through upregulation of epidermal growth factor receptor expression in vascular smooth muscle cells. AB - AIMS: Indoxyl sulfate, a uremic toxin, is considered a risk factor for arteriosclerosis in patients with chronic kidney disease (CKD). We previously reported the actions of indoxyl sulfate including crosstalk with platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells (VSMCs). The present study examines whether indoxyl sulfate enhances angiotensin II (Ang II) signaling because serum levels of Ang II are elevated in patients with CKD. MAIN METHODS: The effect of indoxyl sulfate and Ang II on phosphorylation of ERK and epidermal growth factor receptor (EGFR), and migration were determined using VSMCs. The expression of EGFR was determined using not only VSMCs but also artery of normal, uremic, and indoxyl sulfate-administrated uremic rats. KEY FINDINGS: Ang II-dependent phosphorylation of ERK and EGFR, and migration of VSMCs were augmented by a prior 24-h incubation with indoxyl sulfate even in the absence of indoxyl sulfate during Ang II stimulation. The expression of EGFR was increased in indoxyl sulfate-stimulated cultured VSMCs. In arterial VSMCs of rats, serum levels of indoxyl sulfate reflected the expression level of EGFR. The upregulated EGFR expression by indoxyl sulfate was suppressed by the antioxidant, N acetylcysteine. An EGFR inhibitor, AG1478, repressed the enhancement of Ang II induced cellular effects by indoxyl sulfate. Taken together, these findings indicate that indoxyl sulfate enhances Ang II signaling through reactive oxygen species-induced EGFR expression. SIGNIFICANCE: The actions of indoxyl sulfate including crosstalk with Ang II signaling may be closely involved in the pathogenesis of CKD associated with arteriosclerosis. PMID- 22781708 TI - ERK inhibition enhances TSA-induced gastric cancer cell apoptosis via NF-kappaB dependent and Notch-independent mechanism. AB - AIMS: To analyze the combined impact of the histone deacetylase inhibitor (HDACI) Trichostatin A (TSA) and the extracellular-signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 on gastric cancer (GC) cell line SGC7901 growth. MAIN METHODS: SGC7901 cells were treated with TSA, PD98059 or with a TSA-PD98059 combination. Effects of drug treatment on tumor cell proliferation, apoptosis, cell cycle progression, and cell signaling pathways were investigated by MTS assay, flow cytometry, Western blotting, chromatin immunoprecipitation (ChIP) assay, electrophoretic mobility shift assay (EMSA), and luciferase reporter assay, respectively. KEY FINDINGS: PD98059 enhanced TSA-induced cell growth arrest, apoptosis and activation of p21(WAF1/CIP1), but reversed TSA-induced activation of ERK1/2 and nuclear factor-kappaB (NF-kappaB). TSA alone up-regulated Notch1 and Hes1, and down-regulated Notch2, but PD98059 did not affect the trends of Notch1 and Notch2 induced by TSA. Particularly, PD98059 did potentiate the ability of TSA to down-regulate phospho-histone H3 protein, but increased levels of the acetylated forms of histone H3 bound to the p21(WAF1/CIP1) promoter, leading to enhanced expression of p21(WAF1/CIP1) in SGC7901 cells. SIGNIFICANCE: PD98059 synergistically potentiates TSA-induced GC growth arrest and apoptosis by manipulating NF-kappaB and p21(WAF1/CIP1) independent of Notch. Therefore, concomitant administration of HDACIs and ERK1/2 inhibitors may be a promising treatment strategy for individuals with GC. PMID- 22781709 TI - Role of thymulin on the somatotropic axis in vivo. AB - AIMS: There is clear evidence for the existence of a bi-directional thymus somatotropic axis and several studies suggest that the thymic peptide thymulin may be involved in this communication. We undertook to assess the impact of serum thymulin immunoneutralization in C57BL/6 mice and that of neonatal thymulin gene therapy (NTGT) in nude mice on body weight (BW) gain and on the histomorphometric profile of the somatotrope population. MAIN METHODS: Immunoneutralization of thymulin was done from postnatal day 1 to 35 by i.p. injections of rabbit anti thymulin serum (alpha-FTS) and normal rabbit serum (NRS) in controls. NTGT was implemented in nudes using an adenoviral vector expressing a synthetic gene for thymulin (RAd-FTS). On postnatal day 1, heterozygous (nu/+) and homozygous (nu/nu) pups received a single bilateral i.m. injection either RAd-FTS or RAd-GFP (a control vector expressing green fluorescent protein). BW gain was recorded and at the end of the study the pituitaries were immunostained for growth hormone (GH). Serum GH and thymulin were determined by radioimmunoassay and bioassay, respectively. KEY FINDINGS: Thymulin immunoneutralization induced a significant decrease in BW gain, serum GH and somatotrope cell density as well as an increase in somatotrope cell size. NTGT markedly increased BW gain, serum thymulin (P<0.01) and somatotrope cell and volume density in nu/nu mice. SIGNIFICANCE: Our results suggest that thymulin plays a relevant physiological role on the thymus somatotropic axis in mice. PMID- 22781710 TI - Diagnostic tests and neurology care for Medicare beneficiaries with seizures: differences across racial groups. AB - BACKGROUND: Seizures and epilepsy are common in older adults especially in some minorities. Despite the importance of medical care to maximize seizure control, little is known about its quality across racial groups. One indicator of quality care is the receipt of electroencephalograms (EEG), and magnetic resonance imaging (MRIs) or computer tomography scans (CTs) after a first seizure. Neurologists' care is also important, given associated diagnosis and treatment challenges in older patients. OBJECTIVE: To examine seizure-related care in the year after a first seizure for Medicare beneficiaries by race. RESEARCH DESIGN: Retrospective administrative claims analysis for 186,547 beneficiaries with claims for seizure or epilepsy in 2003-2005. Logistic regressions determined the association between care and race (White, Asian, African and Native Americans) adjusting for beneficiary, seizure, and community factors. MEASURES: EEGs, CTs or MRIs, and neurology visits. RESULTS: About 60% received EEGs, 80% had MRIs or CT scans, and only 55.9% had an EEG and CT scan or an MRI. CT use (74%) was higher than MRI use (41%). About 79% had neurology visits. Compared with Whites, Native Americans were less likely to have neurology visits (66.9% vs. 78.8%; adjusted odds ratio: 0.72; 95% CI, 0.55-0.92). No clinically significant differences (>5%) were found for care received by other minorities compared with Whites. CONCLUSIONS: Medicare beneficiaries with new-onset seizures commonly visit a neurologist, with some groups lagging behind. Use of some diagnostic tests is less common. Studies should continue investigating the quality of medical care for older adults with seizures. PMID- 22781711 TI - Detection of cardiac geometry via difference intensity of echocardiogram images. AB - Echocardiogram is an ultrasound image of the heart that demonstrates the size, motion and composition of cardiac structures and is also used to diagnose various abnormalities of the heart including abnormal chamber size, shape and congenital heart disease. Echocardiography provides important morphological and functional details of the heart. Most of the presented automatic cardiac disease recognition systems that use echocardiograms based on defective anatomical region detection. In this paper we present a simple technique for cardiac geometry detection via echocardiogram images which conquer these borders and exploits cues from cardiac structure. To demonstrate the effectiveness of this technique, we present results for cardiac geometry detection through difference intensity of echocardiogram images. We have developed a simple program code for the prediction of cardiac geometry using difference intensity of echocardiogram images. With this code, users can generate node or point for detection of cardiac geometry as ventricle and atrium in size, shape and location. PMID- 22781712 TI - [Evaluation of the impact of R-CHOP chemotherapy on efficacy, safety and prognosis in newly diagnosed diffuse large B-cell lymphoma patients and its prognostic impact: a multicenter retrospective study with long term follow-up]. AB - OBJECTIVE: To evaluate the efficacy, safety and prognostic impact of rituximab plus CHOP (R-CHOP) regimen on patients with diffuse large B-cell lymphoma (DLBCL), to access the impact of R-CHOP on patients' prognosis and to compare that with CHOP regimen. METHODS: Five hundred and seven newly diagnosed DLBCL patients were enrolled from Jan. 1, 2000 to May 1, 2010. Patients were administered with 6 cycles of CHOP or at least 4 cycles of R-CHOP treatments. Rituximab was administered intravenously on day 1 at a dose of 375 mg/m(2). The typical CHOP regimen include cyclophosphamide (750 mg/m(2), IV), doxorubicin (50 mg/m(2), IV) and vincristine (1.4 mg/m(2), IV, maximum 2 mg) and prednisone (60 - 100 mg, oral, day 3 - 7). The complete response (CR) rates, overall response (OR) rates, and side events of these 2 groups were compared. RESULTS: Of the 411 analyzable patients, 224 received CHOP regimen and 187 received R-CHOP regimen. CR rate for R-CHOP group and CHOP group was 77.01% and 71.43%, respectively. OR rate in R-CHOP group was higher than that in the CHOP group (95.19% vs 87.95%, P = 0.007). The median follow-up time of R-CHOP group was 28.1 months vs that of 35.2 months in CHOP group. There was significant difference in progression free survival (PFS) and overall survival (OS) between 2 groups (P = 0.018 and 0.034, respectively). At the end of follow-up, the estimated median PFS in R-CHOP group had not been reached, while that was 84.8 months in CHOP group. The median OS in both groups had not yet been reached. The adverse events in R-CHOP group were similar with that in CHOP group. CONCLUSIONS: R-CHOP is a safe and effective regimen for management of newly diagnosed DLBCL, with a better remission rate, PFS and OS. PMID- 22781713 TI - [Determination of hematopoietic clonality by detection of multiple X-linked gene exonic polymorphic loci using transcription-based clonality assays]. AB - OBJECTIVE: To explore the frequencies of heterozygosity in X-linked G6PD, P55, BTK, and FHL-1 gene exonic polymorphic loci among Chinese females and the value of determination of hematopoietic clonality by detection of these X-chromosome exonic polymorphisms based on X-chromosome inactivation patterns (XCIP) transcription-based clonality assays (TCA). METHODS: Genomic DNA was extracted from peripheral blood of 446 Chinese healthy females. Allele-specific PCR (ASPCR) or PCR-restriction enzyme digestion method was applied for detecting G6PD, P55, BTK and FHL-1 polymorphisms. Those heterozygotic loci were used as markers to examine the hematopoietic clonality of bone marrow mononuclear cells by TCA from essential thrombocythemia (ET) patients with JAK2V617F mutation and myelodysplastic syndrome (MDS) patients with abnormal karyotype. RESULTS: Among the total 446 genomic DNA samples, the frequencies of heterozygosity in G6PD, P55, BTK and FHL-1 loci were 12.8%, 29.4%, 52.0% and 46.4%, respectively. About 81.4% of females were heterozygous at one or more loci. All 10 ET patients with JAK2V617F mutation and 2 MDS patients with abnormal karyotype, which were heterozygotic in either locus, had monoclonal/oligoclonal hematopoiesis. CONCLUSION: Clonality detection based on X chromosome inactivation patterns transcription based clonality assays is applicable to about 80% of Chinese females. PMID- 22781714 TI - [Langerhans cell sarcoma: a case report and literature review]. AB - OBJECTIVE: To explorer the clinical features, diagnosis and therapy of Langerhans cell sarcoma (LCS). METHODS: The clinical data of a case of LCS originated from cervical lymph nodes was analyzed. The pathological biopsy was studied by cell morphology, immunohistochemistry and electron microscopy, and the related literature was reviewed. RESULTS: The giant tumor cells were characterized by markedly malignant proliferation, irregular nuclei and obviously chromatin abnormality, the positive S-100, CD1a and Langerin (CD207) tumor cells were revealed by immunohistochemistry, and Birbeck granules could be found by electron microscopy. All of them supported the diagnosis of LCS. The patient's condition progressed rapidly and died of multiple organ failure in a short time. CONCLUSION: LCS is an extremely rare neoplastic proliferation of Langerhans cells with overtly malignant cytologic features and spreads aggressively. The diagnosis of LCS mainly relies on pathological cell morphology, immunohistochemistry and electron microscopy if necessary. The treatment includes chemotherapy, surgery and radiotherapy, etc, but lack of generally accepted optimal treatment regimen currently. In short, LCS has intensive invasiveness and poor prognosis. PMID- 22781715 TI - [Congenital dyserythropoietic anemia type II: a case report and literature review]. AB - OBJECTIVE: To investigate the clinical and laboratory features of congenital dyserythropoietic anemia type II (CDA-II) in order to improve the recognition of the disease. METHODS: A case of CDA-II was reported and the related literatures were reviewed. RESULTS: The 32-years old female presented with moderate anemia, jaundice and hepatosplenomegaly from her childhood and was misdiagnosed as hereditary spherocytosis for a long time. There were no increased reticulocytes in the peripheral blood and her bone marrow showed erythroid hyperplasia with 43% of binucleated erythroblasts. Electron microscopy examination revealed stretches of double membrane lining the inner surface of the erythroblast cell membrane. CONCLUSIONS: CDA-II is a rare congenital anemia characterized by ineffective erythropoiesis with unique laboratory features, and is relatively easy to be misdiagnosed. It is necessary to improve the awareness of CDA-II, and to set-up its responsible gene analysis, i.e., CDAN2 gene and SEC23B gene detection. PMID- 22781716 TI - [Expression and clinical significance of Notch1 on the membrane of bone marrow CD38(+)CD138(+) plasma cells in the patients with multiple myeloma]. AB - OBJECTIVE: To investigate the expression of Notch1 on the membrane of bone marrow CD38(+)CD138(+) plasma cells in the patients with multiple myeloma (MM), and explore the importance of Notch signaling pathway in the formation and progression of MM. METHODS: Thirty three MM patients and 15 healthy controls were enrolled in this study. The expression of Notch1 on the membrane of bone marrow CD38(+)CD138(+) and CD38(+)CD138(-) plasma cells were analyzed by flow cytometry. The clinical data of MM patients were also analyzed. RESULTS: The ratio of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients was (60.21 +/- 25.06)% which was significantly higher than those of CD38(+)CD138(-) plasma cells of MM patients (39.84 +/- 18.94)% (P = 0.000) and controls (38.34 +/- 19.39)% (P = 0.004). There was no statistical difference between the two latter groups (P > 0.05). The expression of Notch1 on CD38(+)CD138(+)plasma cells from 24 newly diagnosed MM patients was correlated to the level of malignant plasma cells in there bone marrow (r = 0.914, P = 0.000), serum level of lactate dehydrogenase (LDH) (r = 0.754, P = 0.007), and beta(2)-MG(r = 0.716, P = 0.013). The ratio of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients who had renal dysfunction was correlated to their abnormal serum creatinine levels. The expression of Notch1 on CD38(+)CD138(+) plasma cells from 17 MM patients who received VD (bortezamib and dexamethasone) chemotherapy was correlated to the ratio of plasma cell reduction after the first VD chemotherapy (r = 0.842, P = 0.000). CONCLUSION: The expression of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients was significantly higher than those of CD38(+)CD138( ) plasma cells of MM patients and controls. Notch1 overexpressed plasma cells were sensitive to the early VD therapy, and correlated to the progression and long term outcome of MM. PMID- 22781717 TI - [Expression and clinical significance of ID1 gene in acute myeloid leukemia]. AB - OBJECTIVE: To explore the expression and clinical significance of ID1 gene in acute myeloid leukemia (AML) patients. METHOD: Real-time quantitative PCR (RQ PCR) was used to test the expression level of ID1 gene in 114 de novo adult AML patients, and the clinical features of these patients were analyzed. RESULTS: ID1 gene transcript levels were detectable in BM mononuclear cells from 114 patients with AML, the median expression level of all samples was 8525 (range: 57 - 11 233 238). There was a statistically significant difference on expression level of ID1 gene among the three different cytogenetic prognosis groups, and the poor prognosis group (median: 36 840, range: 336 - 11 233 238) harbored the significantly higher level of ID1 gene than the intermediate prognosis group (Median: 6630, range: 66 - 1 840 798) (P = 0.006). The expression level of ID1 gene was positively associated with older age (age >= 60 years vs < 60 years, P = 0.002) and higher WBC count (WBC >= 10*10(9)/L vs < 10*10(9)/L, P = 0.005). Young patients (age < 60 years) who were not obtained the complete remission (non-CR) after the first cycle of chemotherapy harbored the high level of ID1 gene (Median: 9537 of non-CR vs 1268 of CR, P = 0.010). CONCLUSIONS: High expression level of ID1 gene was mostly seen in AML patients with adverse cytogenetics and older age (age >= 60 years), and may be associated with poor prognosis of AML. ID1 gene might be a prognostic molecular marker of AML. PMID- 22781718 TI - [Cytogenetic analysis of childhood acute lymphoblastic leukemia]. AB - OBJECTIVE: To characterize the genetic aberrations in pediatric acute lymphoblastic leukemia (ALL). METHODS: Ninety ALL cases were enrolled in the study from January 2009 to November 2011. Chromosome banding analysis and fluorescence in situ hybridization (FISH) were used to detect genetic aberrations. RESULTS: (1) Chromosome analysis: 35 (53.0%) of 66 cases who had metaphase were abnormal, and 24 cases had no metaphase. (2) FISH analysis: among the 31 cases who had normal karyotypes and 24 who had no metaphase detected by chromosome banding technique, 7 (22.6%) and 14 (58.3%) cases were abnormal detected by FISH, respectively. There were no statistically significant differences compared with chromosome analysis (P = 0.655). Among these 55 ALL cases TEL/AML1, bcr-abl and MLL fusion genes were observed in 16 (29.1%), 3(5.5%) and 2(3.6%) cases, respectively. (3) Cytogenetic aberration was observed in 56 of total 90 ALL cases (62.2%). CONCLUSIONS: Cytogenetic changes are common in childhood ALL. Conventional cytogenetic study could reliably detected chromosomal abnormalities for ALL with assessable metaphase. FISH should be used as a complementary method for ALL patients who have poor chromosomal morphology or no metaphase cells, and combination of both methods can improve the detection rate of genetic abnormalities in childhood leukemia. PMID- 22781719 TI - [Comparison of EGIL1998 and WHO2008 criteria for the diagnosis of mixed phenotype acute leukemia]. AB - OBJECTIVE: To explore the relationship between EGIL 1998 and WHO2008 criteria for the diagnosis of mixed phenotype acute leukemia (MPAL). METHODS: The same group patients were diagnosed for MPAL by EGIL 1998 and WHO2008 criteria, respectively. The coincidence rate of diagnosis and therapeutic response of two diagnosis standards were compared. RESULTS: A cohort of 1835 de novo acute leukemia (AL) patients admitted to our hospital from February 1996 to October 2010 were retrospectively analyzed by applying both EGIL1998 and WHO2008 classification criteria. Seventy four patients were diagnosed with MPAL according to EGIL 1998, accounting for 4.0% of all AL cases. The main subtype is M/B (54 cases, 73.0%). While 81 patients were diagnosed as MPAL, accounting for 4.4% based on WHO 2008 criteria. The most common type is also M/B (63 cases, 77.8%). Fifty nine (79.7%) cases met both criteria. In the subtypes of M/B, M/T, M/B/T and B/T, the coincidence rate is 85.2% (46/54), 56.3% (9/16), 0(0/2) and 50.0% (1/2), respectively. In the 1761 cases excluded as MPAL by EGIL1998, 22 cases can be diagnosed as MPAL by WHO 2008 classification. (2) Among the patients diagnosed as B/M MPAL by WHO2008, 13 were MPAL with t (9; 22) (q34; q11.2)/BCR-ABL1, 1 was MPAL with t (v; 11q23)/MLL-rearranged, 49 was B/myeloid not otherwise specified (NOS), 14 was T/myeloid NOS and 4 was MPAL NOS-rare types. (3) The overall final complete remission rate of the patients diagnosed by EGIL1998, 2008 WHO, met both criteria, EGIL1998 but excluded by 2008 WHO and by 2008 WHO but excluded by EGIL1998 was 69.0%, 73.5%, 73.5%, 44.4% and 73.7%, respectively, with no significant difference between any two groups based on chi(2) test (P > 0.05). CONCLUSIONS: EGIL 1998 and WHO2008 criteria have reciprocity in the diagnosis of MPAL. PMID- 22781720 TI - [A case report of adult onset of primary hemophagocytic syndrome with literature review]. AB - OBJECTIVE: To introduce the clinical manifestations and laboratory tests of adult onset of primary hemophagocytic syndrome (HPS), and to investigate the essentials of diagnosis and the genotype characteristics in adult onset patient. METHODS: The definite diagnosis of HPS was made according to HLH-2004. Exons of PRF1, STX11, UNC13D, SH2D1A and RAB27A genes coding region were amplified using polymerase chain reaction. RESULTS: A 48-year-old man was admitted to our hospital because of recurrent fever, pancytopenia and lymph node enlargement. His laboratory test revealed bone marrow hemophagocytosis, elevated ferritin level (2000 ug/L), reduced level of NK cell activity (20.13%) and elevated soluble CD25 level (12277 U/ml). Based on the HLH-2004 diagnostic criteria, the patient was diagnosed as HPS. The patient had viral infection, and no other primary disease was identified that would cause HPS. The patient responded poorly to anti-viral therapy. DNA sequencing was used to confirm that perforin gene mutations might be one of the causes of the patient suffered from primary HPS. CONCLUSIONS: Although primary HPS usually affects infants and young children, it also occurred in teens and adults. It is essential to perform genetic screenings to patient whose illnesses recur with unknown causes. In addition, detection of molecular genetic alterations can be used to distinguish primary HPS from acquired HPS. PMID- 22781721 TI - [Acquired factor V inhibitor: 3 cases report and literature review]. AB - OBJECTIVE: To better understand the acquired factor V (FV) inhibitors. METHODS: The clinical features, laboratory manifestations, treatment options and prognosis of 3 cases were reported and related literature were reviewed. RESULTS: All the 3 patients were older than 50 years without family history and related disease. Their clinical manifestations included spontaneously mucous bleeding, hematuria, epistaxis and encephalic bleeding. Laboratory test showed prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). The FV levels decreased and the presence of FV inhibitor was confirmed by Bethesda method. All patients were treated with glucocorticoid and immunosuppressive agents. The haemorrhages of two patients stopped but their coagulation test and FV level recovered slowly. One patient died from encephalic bleeding. CONCLUSIONS: Acquired FV inhibitor is a rare coagulation disorder with variable clinical symptoms. Immunosuppressive agents are effective to eliminate the inhibitors. The prognosis of acquired FV inhibitors seemed to be strictly related to the basic disease. PMID- 22781722 TI - [Identification of a novel large deletion of factor subunit A mRNA associated with hereditary factor deficiency]. AB - OBJECTIVE: To analyze the expressed mRNA of the factor subunit A (FA) in monocyte in a hereditary factor (F) deficiency family. METHODS: The F A mRNA of the proband and the other family members was analyzed by RT-PCR, semi-quantitative RT PCR, cloning and sequencing. The three dimensional structure of the protein was predicted by SWISS-MODEL and viewed by RASMIOL. RESULTS: (1) A large in frame deletion from codons 11 to 279, spanning from exon 2 to 7 of F A (DelCD11-279), was identified in the proband at mRNA level and a truncated protein is predicted composed of 464 amino acids. Compared with the normal and the other families, the proband showed lower level of F A mRNA in RT-PCR. (2) SWISS-MODEL analysis showed that the truncated protein lacked the beta-sandwich and a part of catalytic core, resulting in loss of the normal catalytic domains. CONCLUSION: DelCD11-279 of F A mRNA is associated with hereditary F deficiency. The reduced expressing level of F A gene is one of the causes resulting in F deficiency in the patients. PMID- 22781723 TI - [Clinical study of umbilical cord-derived mesenchymal stem cells for treatment of nineteen patients with steroid-resistant severe acute graft-versus-host disease]. AB - OBJECTIVE: To evaluate the safety and efficacy of umbilical cord-derived mesenchymal stem cells (MSCs) infusion in patients with steroid-resistant severe acute graft-versus-host disease (aGVHD). METHODS: A total of 19 patients with steroid-resistant severe aGVHD received MSCs infusion treatment. The treatment response, transplantation-related mortality, events associated with infusion and relapse rate were analyzed. RESULTS: Two patients with grade II, 5 patients with grade III and 12 patients with grade IV aGVHD received a total of 58 infusions of MSCs. The mean total dose of MSCs was 2.13 (range 0.60 - 7.20)*10(6) cells per kg bodyweight. Seven patients received one infusion, 2 patients received two infusions, and 10 patients received three or more infusions. Eleven patients had a complete response and 4 had a partial response and 4 had no response. No patients had side-effects during or immediately after infusions, and no MSCs related tumorigenesis was detected to date. Eleven patients survived and 8 died, 4 for aGVHD, 1 for infection and 2 for aGVHD with concomitant infection and 1 for underlying leukemia relapse. The cell viability of freshly prepared MSCs is 93% (92% - 95%) by trypan blue staining. The cell viability of programmatically frozen and thawed MSCs is 72% (70% - 74%). CONCLUSION: Infusion of umbilical cord derived MSCs expanded in vitro is an effective therapy for patients with steroid resistant severe aGVHD without negative impact on relapse. Freshly prepared MSCs are superior to frozen and thawed cells in terms of cell viability. PMID- 22781724 TI - [Effect of IGFBP7 gene down-regulation on leukemia cells]. AB - OBJECTIVE: To explore the effect of down-regulation of insulin-like growth factor binding protein 7 (IGFBP7) on the proliferation and invasiveness of leukemia cell line U937 cells. METHODS: Three pairs of double-strand siRNA targeting IGFBP7 gene were transfected into SMMC7721 cells to select the most efficient one for U937 cells. qRT-PCR and Western blot were used to detect the expression of IGFBP7 in U937 cells after transiently transfected with siRNA of IGFBP7. Cell proliferation, adhesion, trans-endothelial migration and invasion were performed in transfected cells and control groups. RESULTS: After transfected with siRNA of IGFBP7 in U937 cells, the ability of cell proliferation was significantly decreased at 24 h (0.580 +/- 0.159) compared to that of parental cells and scramble negative control (1.049 +/- 0.274, 0.946 +/- 0.195, respectively) (P < 0.01). Adhesion of U937 cells transfected with IGFBP7 gene specific siRNA to ECV304 cells was significantly lower than that of the control groups (0.247 +/- 0.031 vs 0.406 +/- 0.023 and 0.395 +/- 0.011) (P < 0.01). Transendothelial membrane of U937 cells into the bottom of the 24-well plate for experimental group were less than those in the control groups ?[(0.387 +/- 0.021)*10(5) vs (1.017 +/- 0.031)*10(5) and (0.908 +/- 0.027)*10(5)?]. Cells adherent to the matrigel for experimental group were less than those in the control groups ?[(0.197 +/- 0.098)*10(5) vs (0.493 +/- 0.067)*10(5) and (0.469 +/- 0.083)*10(5)?]. The difference was significant (P < 0.01). CONCLUSION: IGFBP7 gene plays a contributing role in leukemogenesis involving in leukemic cells' proliferation and interaction with endothelial cells through adhesion, invasion and migration. PMID- 22781725 TI - [A retrospective study of chronic myelocytic leukemia treatment with imatinib and interferon-alpha]. AB - OBJECTIVE: To investigate the clinical effect of chronic myelocytic leukemia (CML) patients treated with imatinib (IM) and interferon (IFN)-alpha. METHODS: One hundred and fifty five CML patients at chronic phase were included in the study. All patients were divided into two groups according to treatment regimen: IM + IFN group and IM group. Complete cytogenetic response (CCyR) rate, major molecular response (MMR) rate, complete molecular response (CMR) rate, overall survival (OS) and progression free survival (PFS) were observed and compared in both groups. RESULTS: The CCyR rate was higher in the IM + IFN group than that in the IM group at 6 months (60.6% vs 41.6%, P < 0.05), but no difference was observed later on. The MMR + CMR rate was higher in the IM + IFN group than that in the IM group at 6 months and 12 months (71.2% vs 34.8%, 77.3% vs 52.8%, respectively, P < 0.05), but no difference after that. After stratification according to Sokal risk, the CCyR rate of low- and intermediate-risk patients was higher in the IM + IFN group than that in the IM group at 6 months (77.8% vs 52.6%, 75.0% vs 46.7%, P < 0.05), but not from 12 months on; the MMR + CMR rate of low- and intermediate-risk patients was higher in the IM + IFN group than that in the IM group at 6 months and 12 months (85.2% vs 36.8%, 90.0% vs 36.7%, P < 0.05; 88.9% vs 57.9%, 90.0% vs 56.7%, P < 0.05), but not from 24 months on. There was no significant difference in high-risk patients. OS in IM and IM + IFN group at 6, 12, 24 and 36 months was 100%, 100%, 96.8% and 90.0%, and 100%, 100%, 97.9% and 93.1%, respectively. PFS in IM and IM + IFN group at 6, 12, 24 and 36 months was 97.8%, 95.5%, 91.9% and 85.5%, and 98.5%, 95.5%, 91.5% and 86.2%, respectively. There was no significant difference in OS (u = 0.427, P = 0.514) or PFS (u = 0.556, P = 0.456). The side effects in both groups included pancytopenia, edema, weight gain, ostalgia, rash and muscle spasm. In addition, patients in the IM + IFN group suffered from flu-like symptoms, impaired liver function, abnormal thyroid function and extremity sensory disturbance. It seemed that grade III or IV pancytopenia occurred more commonly in the patients in the IM + IFN group, however, there was no statistically significance. CONCLUSIONS: The response to IM + IFN is more rapid than that to IM alone, especially for the low- and intermediate-risk patients. It seems no benefit of the addition of IFN to treatment of high-risk patients. During the period of 36 months, survival rate in the IM + IFN group is not higher than that in IM group, and it is possible to increase the side effects of pharmaceutical drugs. PMID- 22781726 TI - [A case of hairy cell leukemia complicated by breast cancer in remission]. PMID- 22781727 TI - [Expression and clinical significance of Bmi-1 gene in multiple myeloma]. PMID- 22781728 TI - [Clinical study on relationship between protein tyrosine kinase JAK2 V617F mutation and high altitude polycythemia]. PMID- 22781729 TI - [Effects of scorpion venom component III on cell cycle arrest and NF-kappaB activity in THP-1 cells]. PMID- 22781730 TI - [A case of acute lymphoblastic leukemia complicated by autoimmune hemolytic anemia]. PMID- 22781731 TI - [Biological effects of sCD40L on acute myeloid leukemia cells HL-60 and its mechanism]. PMID- 22781732 TI - [Studies on Bcl-xl, Bax and Bid expressions and erythroblasts apoptosis in chronic altitude sickness]. PMID- 22781733 TI - [Biological characteristics of rat adipose-derived stem cells and their supporting capacities in ex vivo expansion of rat hematopoietic stem/progenitor cells]. PMID- 22781734 TI - [The study model for prognosis of acute leukemia and myelodysplastic syndrome]. PMID- 22781735 TI - [Capillary leak syndrome (CLS) induced by G-CSF: 3 cases report and literature review]. PMID- 22781736 TI - [Clinical analysis of 12 lymphoplasmacytic lymphoma cases]. PMID- 22781737 TI - [Progress of (18)F-FDG PET/CT application in the management of lymphoma]. PMID- 22781738 TI - [Research status on tumor stem cells of multiple myeloma]. PMID- 22781739 TI - [Expert consensus on diagnosis and treatment of myelodysplastic syndrome]. PMID- 22781740 TI - Improved anemia is associated with favorable long-term clinical outcomes in patients undergoing PCI. AB - BACKGROUND: Anemia is associated with an increased risk of mortality in patients who underwent percutaneous coronary intervention (PCI) in the bare-metal stent era. However, there have been no data concerning the clinical importance of anemia improvement during the follow-up period after discharge from the hospital during the drug-eluting stent era. METHODS AND RESULTS: To assess anemia, the hemoglobin level was measured at the time of index PCI with drug-eluting stents and at the subsequent outpatient visit between 3 and 12 months later. Improvement of anemia was defined by the normalization of the hemoglobin level at the follow up laboratory examination. We analyzed 4300 patients who were tested for initial and follow-up hemoglobin levels. We compared major adverse cardiac and cerebrovascular events (MACCE) between the normal group and the anemia group and between the improved anemia group and the sustained anemia group. The median follow-up period was 25.4 months. There was poorer clinical outcome in the anemia group than in the normal group in terms of MACCE (adjusted hazard ratio 1.479, 95% confidence interval 1.025-2.134, P=0.037). Furthermore, the sustained anemia group showed poorer MACCE than did the improved anemia group (hazard ratio 3.558, 95% confidence interval 2.285-5.539, P<0.0001). On the basis of the multivariate Cox hazard regression model and propensity-score matching, the overall findings were consistent between sustained and improved anemia groups. CONCLUSION: The follow-up of hemoglobin level is important, and improvement of anemia is associated with favorable long-term clinical outcomes. PMID- 22781741 TI - Platelet protease-activated receptor antagonism in cardiovascular medicine. AB - Ischemic heart disease remains the number one cause of death in the world despite advances in invasive and pharmacologic therapies. An ongoing area of research is the central role of platelets in atherothrombosis. Many therapeutic strategies have been developed over the last few decades affecting different platelet receptors to alter platelet-mediated thrombosis including targeting the receptors for thromboxane A(2), adenosine diphosphate, and fibrinogen. However, despite the use of pharmacologic agents directed at these pathways, residual morbidity and mortality still exist. Therefore, identifying agents that more favorably balance a reduction in ischemic events while minimizing bleeding events is an ongoing mission. Thrombin is known to be the most potent stimulant of platelet-mediated thrombosis whose action on the platelet is through a family of receptors known as the protease-activated receptors (PARs). Activation through the PAR-1 receptor, in particular, results in an early and intense response by the platelet to thrombin, and it is the primary thrombin receptor on platelets, thus making it a potentially desirable target for therapy. Most recently, two PAR-1 antagonists, atopaxar and vorapaxar, have been tested in clinical trials. Generally, the results show a reduction in ischemic event rates, but an increase in bleeding event rates. This article will summarize the current state of the literature and consider the role these drugs might play in the future for the prevention of ischemic heart disease events. PMID- 22781743 TI - Ultrafast excited state deactivation of doped porous anodic alumina membranes. AB - Free-standing, bi-directionally permeable and ultra-thin anodic aluminum oxide (AAO) membranes establish attractive templates (host) for the synthesis of nano dots and rods of various materials (guest). This is due to their chemical and structural integrity and high periodicity on length scales of 5-150 nm which are often used to host photoactive nano-materials for various device applications including dye-sensitized solar cells. In the present study, AAO membranes are synthesized by using electrochemical methods and a detailed structural characterization using FEG-SEM, XRD and TGA confirms the porosity and purity of the material. Defect-mediated photoluminescence quenching of the porous AAO membrane in the presence of an electron accepting guest organic molecule (benzoquinone) is studied by means of steady-state and picosecond/femtosecond resolved luminescence measurements. Using time-resolved luminescence transients, we have also revealed light harvesting of complexes of porous alumina impregnated with inorganic quantum dots (Maple Red) or gold nanowires. Both the Forster resonance energy transfer and the nano-surface energy transfer techniques are employed to examine the observed quenching behavior as a function of the characteristic donor-acceptor distances. The experimental results will find their relevance in light harvesting devices based on AAOs combined with other materials involving a decisive energy/charge transfer dynamics. PMID- 22781742 TI - Medication discovery for addiction: translating the dopamine D3 receptor hypothesis. AB - The dopamine D3 receptor (D3R) has been investigated as a potential target for medication development to treat substance use disorders (SUDs) with a particular focus on cocaine and methamphetamine. Currently, there are no approved medications to treat cocaine and methamphetamine addiction and thus developing pharmacotherapeutics to complement existing behavioral strategies is a fundamental goal. Novel compounds with high affinity and D3R selectivity have been evaluated in numerous animal models of drug abuse and favorable outcomes in nonhuman primate models of self-administration and relapse have provided compelling evidence to advance these agents into the clinic. One approach is to repurpose drugs that share the D3R mechanism and already have clinical utility, and to this end buspirone has been identified as a viable candidate for clinical trials. A second, but substantially more resource intensive and risky approach involves the development of compounds that exclusively target D3R, such as GSK598809 and PG 619. Clinical investigation of these drugs or other novel D3R selective agents will provide a better understanding of the role D3R plays in addiction and whether or not antagonists or partial agonists that are D3R selective are effective in achieving abstinence in this patient population. PMID- 22781744 TI - Regulation of the DH-PH tandem of guanine nucleotide exchange factor for Rho GTPases by phosphoinositides. AB - Rho GTPases act as molecular switches central in cellular processes such as cytoskeleton dynamics, migration, cell proliferation, growth or survival. Their activation is tightly regulated downstream of cell surface receptors by Guanine nucleotide Exchange Factors (GEFs), that are responsible for the specificity, the accuracy, and the spatial restriction of Rho GTPases response to extracellular cues. Because there is about four time more RhoGEFs that Rho GTPases, and GEFs do not always show a strict specificity for GTPases, it is clear that their regulation depends on specific interactions with the subcellular environment. RhoGEFs bear a peculiar structure, highly conserved though evolution, consisting of a DH-PH tandem, the DH (Dbl homology) domain being responsible for the exchange activity. The function of the PH (Pleckstrin homology) domain known to bind phosphoinositides, however, remains elusive, and reports are in many cases rather confusing. This review summarizes data on the regulation of RhoGEFs activity through interaction of the PH-associated DH domain with phosphoinositides which are considered as critical players in the spatial organization of major signaling pathways. PMID- 22781745 TI - Diacylglycerol kinase beta in neurons: functional implications at the synapse and in disease. AB - Phosphoinositide cycle plays a pivotal role in neuronal signal transduction. In this cycle, diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to yield phosphatidic acid (PA). DG and PA acts as important second messengers that regulate distinct cascade of cellular events. Previous studies have disclosed that DGK consists of a family of isozymes that differ in their structure, enzymatic property, gene expression, subcellular localization, and binding partner. Intriguingly, most if not all DGK isozymes are abundantly expressed in the brain, suggesting important roles of this enzyme family in brain function. Of DGKs, DGKbeta was the first enzyme identified as being expressed in a neuronal population in the brain. This review focuses on recent findings of DGKbeta at the molecular, cellular, and organismal levels together with pathological implications in brain function and disease. PMID- 22781746 TI - The newcomer in the integrin family: integrin alpha9 in biology and cancer. AB - Integrins are heterodimeric transmembrane receptors regulating cell-cell and cell extracellular matrix interactions. Of the 24 integrin heterodimers identified in humans, alpha9beta1 integrin is one of the least studied. alpha9, together with alpha4, comprise a more recent evolutionary sub-family of integrins that is only found in vertebrates. Since alpha9 was thought to have similar functions as alpha4, due to many shared ligands, it was a rather overlooked integrin until recently, when its importance for survival after birth was highlighted upon investigation of the alpha9 knockout mouse. alpha9beta1 is expressed on a wide variety of cell types, interacts with many ligands for example fibronectin, tenascin-C and ADAM12, and has been shown to have important functions in processes such as cell adhesion and migration, lung development, lymphatic and venous valve development, and in wound healing. This has sparked an interest to investigate alpha9beta1-mediated signaling and its regulation. This review gives an overview of the recent progress in alpha9beta1-mediated biological and pathological processes, and discusses its potential as a target for cancer diagnosis and therapy. PMID- 22781747 TI - Secretomics for skeletal muscle cells: a discovery of novel regulators? AB - Metabolic tissues, including skeletal muscle, adipose tissue and the digestive system, dynamically secrete various factors depending on the metabolic state, communicate with each other and orchestrate functions to maintain body homeostasis. Skeletal muscle secretes cytokines such as interleukin-6 (IL-6), IL 15, fibroblast growth factor-21 (FGF21) and IL-8. These compounds, myokines, play important roles in biological homeostasis such as energy metabolism, angiogenesis and myogenesis. New technological advances have allowed secretomics - analysis of the secretome - to be performed. The application of highly sensitive mass spectrometry makes qualitative and quantitative analysis of the secretome of skeletal muscle possible. Secretory proteins derived from skeletal muscle cells under various conditions were analyzed, and many important factors were suggested. In-depth studies of the secretome from metabolic cells in various conditions are strongly recommended. This study will provide information on methods of novel communication between metabolic tissues. PMID- 22781748 TI - How inositol pyrophosphates control cellular phosphate homeostasis? AB - Phosphorus in his phosphate PO(4)(3-) configuration is an essential constituent of all life forms. Phosphate diesters are at the core of nucleic acid structure, while phosphate monoester transmits information under the control of protein kinases and phosphatases. Due to these fundamental roles in biology it is not a surprise that phosphate cellular homeostasis is under tight control. Inositol pyrophosphates are organic molecules with the highest proportion of phosphate groups, and they are capable of regulating many biological processes, possibly by controlling energetic metabolism and adenosine triphosphate (ATP) production. Furthermore, inositol pyrophosphates influence inorganic polyphosphates (polyP) synthesis. The polymer polyP is solely constituted by phosphate groups and beside other known functions, it also plays a role in buffering cellular free phosphate [Pi] levels, an event that is ultimately necessary to generate ATP and inositol pyrophosphate. Although it is not yet clear how inositol pyrophosphates regulate cellular metabolism, understanding how inositol pyrophosphates influence phosphates homeostasis will help to clarify this important link. In this review I will describe the recent literature on this topic, with in the hope of inspiring further research in this fascinating area of biology. PMID- 22781749 TI - Hydrogen and halogen bonding drive the orthogonal self-assembly of an organic framework possessing 2D channels. AB - Orthogonal self-assembly of an open organic framework showing 2D channels has been obtained by combining hydrogen and halogen bonding. The framework is able to host various guest molecules with a diverse set of steric demands and substitution patterns, and survives single-crystal-to-single-crystal guest exchanges from liquid and gas phases. PMID- 22781750 TI - Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor beta pathway. AB - Protein phosphatases play a key role in balancing the cellular responses to the transforming growth factor-beta (TGFbeta) signals. Several protein phosphatases have been attributed roles in the regulation of the TGFbeta pathway. Among these, PPM1A is the only phosphatase reported to dephosphorylate SMAD2/3 in the nucleus. However we observed PPM1A exclusively in the cytoplasmic fractions independently of TGFbeta treatment in all cells tested. These observations imply that a bona fide nuclear SMAD2/3 phosphatase remains elusive. In this study, we report a role for protein phosphatase 5 (PP5) in the TGFbeta pathway. We identified PP5 as an interactor of SMAD2/3. Interestingly, in mouse embryonic fibroblast cells derived from PP5-null mice, TGFbeta-induced transcriptional responses were significantly enhanced. Rather surprisingly, this enhancement is due to the increased levels of SMAD3 protein observed in PP5-null MEFs compared to the wild type. No differences in the levels of SMAD3 transcripts were observed between the wild-type and PP5 null MEFs. While PP5 is capable of dephosphorylating SMAD3-tail in overexpression assays, we demonstrate that its activity is essential in controlling SMAD3 protein levels in MEFs. We propose that PP5 regulates the TGFbeta pathway in MEFs by regulating the expression of SMAD3 protein levels. PMID- 22781751 TI - MiR-20a and miR-106b negatively regulate autophagy induced by leucine deprivation via suppression of ULK1 expression in C2C12 myoblasts. AB - Autophagy is an evolutionarily conserved process responsible for degradation and recycling of cytoplasmic components through the lysosomal machinery. It has been proved to play pivotal roles in cellular homeostasis, cell growth and organism development. Moreover, abnormalities of autophagy have been linked to numerous human pathophysiologies. Emerging evidence has linked leucine deprivation induced protein breakdown to autophagy, but the underlying mechanisms controlling autophagic activity in this process are not fully understood. Here, we demonstrate that two members of the miR-17 microRNA family, miR-20a and miR-106b, may participate in regulating leucine deprivation induced autophagy via suppression of ULK1 expression in C2C12 myoblasts. We showed that leucine deprivation downregulated miR-20a and miR-106b expression via suppression of their transcription factor c-Myc. We discovered the essential autophagy gene ULK1 as cellular target of miR-20a and miR-106b. Treatment of C2C12 cells with the miR 20a or miR-106b mimic decreased the endogenous ULK1 protein levels. Dual luciferase reporter assay confirmed that the miRNA binding sequences in the 3' UTR of ULK1 contribute to the modulation of ULK1 expression by miR-20a and miR 106b. Furthermore, inhibition of ULK1 expression by the miR-20a or miR-106b mimic blunted activation of autophagy induced by leucine deprivation, while suppression of endogenous miR-20a or miR-106b by specific antagomir in C2C12 cells showed normal autophagic activity. Altogether, our data demonstrated that miR-20a and miR-106b regulated autophagy induced by leucine deprivation in C2C12 cells via targeting ULK1. PMID- 22781752 TI - Visceroptosis of the bowel in the hypermobility type of Ehlers-Danlos syndrome: presentation of a rare manifestation and review of the literature. AB - Gastrointestinal complications are common in patients with Ehlers-Danlos syndrome, affecting up to 50% of individuals depending on the subtype. The spectrum of gastrointestinal manifestations is broad and ranges from life threatening spontaneous perforation of the visceral organs to a more benign functional symptoms. Here we describe the clinical and radiographic manifestations of visceroptosis of the bowel, a rare complication of Ehlers Danlos syndrome that is characterized by prolapse of abdominal organs below their natural position. We further review the literature on gastrointestinal complications in the different forms of Ehlers-Danlos syndrome. PMID- 22781753 TI - Mitochondrial DNA m.3242G > A mutation, an under diagnosed cause of hypertrophic cardiomyopathy and renal tubular dysfunction? AB - We present two new patients with the recently described mitochondrial m.3242G > A mutation. Although the mutation is situated next to the well known m.3243A > G mutation, the most common alteration associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, the clinical presentation is quite different, but characteristic. All three m.3242G > A patients presented in the neonatal period with hypertrophic and dilated cardiomyopathy, generalized muscle hypotonia and lactic acidosis. Two additionally had creatine kinase elevation, renal tubular acidosis/dysfunction and showed a mild clinical course with a favourable psychomotor development. The third patient had more neurological involvement and died in infancy. The mutation occurred de novo in the two patients where maternal investigations were performed. The combination of hypertrophic cardiomyopathy and renal tubular acidosis/renal tubular dysfunction is clinically distinctive and may represent a separate entity. PMID- 22781754 TI - Ureteroscopy-assisted retrograde nephrostomy for lower calyx calculi in horseshoe kidney: two case reports. AB - INTRODUCTION: We previously reported on the effectiveness of ureteroscopy assisted retrograde nephrostomy during percutaneous nephrolithotomy and report two cases of lower calyx calculi in horseshoe kidney that were successfully treated with ureteroscopy-assisted retrograde nephrostomy. During the ureteroscopy-assisted retrograde nephrostomy procedure, a ureteroscope is advanced in the desired calyx and a Lawson retrograde nephrostomy puncture wire is inserted. The wire is advanced through the calyx to exit the skin. The wire is then used for the percutaneous dilation. CASE PRESENTATION: Case 1 was a 68-year old man who was shown on radiography to have left lower calyx calculi (19 * 15mm, 7 * 5mm, and 7 * 3mm) in horseshoe kidney. Case 2 was a 36-year-old woman shown on radiography to have a left lower calyx calculus (10 * 8mm) in horseshoe kidney. CONCLUSIONS: Both patients were stone-free after ureteroscopy-assisted retrograde nephrostomy during percutaneous nephrolithotomy. Ureteroscopy-assisted retrograde nephrostomy is a promising procedure for safely and effectively treating lower calyx stones in horseshoe kidney. PMID- 22781755 TI - Photoinduced handedness switching in terahertz chiral metamolecules. AB - Switching the handedness, or the chirality, of a molecule is of great importance in chemistry and biology, as molecules of different handedness exhibit dramatically different physiological properties and pharmacological effects. Here we experimentally demonstrate handedness switching in metamaterials, a new class of custom-designed composites with deep subwavelength building blocks, in response to external optical stimuli. The metamolecule monolayer flips the ellipticity and rotates the polarization angle of light in excess of 10 degrees under optical excitation, a much stronger electromagnetic effect than that of naturally available molecules. Furthermore, the experimentally demonstrated optical switching effect does not require a structural reconfiguration, which is typically involved in molecular chirality switching and is inherently slow. The handedness switching in chiral metamolecules allows electromagnetic control of the polarization of light and will find important applications in manipulation of terahertz waves, such as dynamically tunable terahertz circular polarizers and polarization modulators for terahertz radiations. PMID- 22781756 TI - Two-dome structure in electron-doped iron arsenide superconductors. AB - Iron arsenide superconductors based on the material LaFeAsO(1-x)F(x) are characterized by a two-dimensional Fermi surface (FS) consisting of hole and electron pockets yielding structural and antiferromagnetic transitions at x=0. Electron doping by substituting O(2-) with F(-) suppresses these transitions and gives rise to superconductivity with a maximum T(c) of 26 K at x=0.1. However, the over-doped region cannot be accessed due to the poor solubility of F(-) above x=0.2. Here we overcome this problem by doping LaFeAsO with hydrogen. We report the phase diagram of LaFeAsO(1-x)H(x) (x<0.53) and, in addition to the conventional superconducting dome seen in LaFeAsO(1-x)F(x), we find a second dome in the range 0.21 40 mm Hg (1 mm Hg = 0.133 kPa) at rest. Eisenmenger syndrome was defined when there was a reversed (pulmonary-to systemic) or bidirectional shunt. The clinical characteristics between the patients with/without PAH and Eisenmenger syndrome were compared and their risk factors analyzed with a multivariate Logistic model. RESULTS: The underlying conditions included atrial septal defect (n = 187, 27.0%), ventricular septal defect (n = 456, 65.9%) and patent ductus arteriosus (n = 49, 7.1%). The numbers of patients with PAH-CHD and Eisenmenger syndrome were 329 (47.5%) and 105 (15.2%) respectively. Among the PAH-CHD patients, 31.9% of them had Eisenmenger syndrome. The patients with large shunts were at an elevated risk of PAH. Logistic regression analysis showed that advanced age was an independent risk factor of PAH (OR = 1.04, P < 0.001). Compared with atrial septal defect, ventricular septal defect and patent ductus arteriosus increased the risks of PAH (OR = 2.78, P < 0.001 and OR = 2.50, P < 0.001 respectively). CONCLUSIONS: PAH is a common complication in CHD patients. And ventricular septal defect is the most common pathogenic type of PAH. Advanced age, ventricular septal defect and patent ductus arteriosus are the risk factors of PAH. PMID- 22781766 TI - [Effect of arsenic trioxide and daunorubicin on procoagulant activity of acute promyelocytic leukemia cells]. AB - OBJECTIVE: To explore the effect of arsenic trioxide (ATO) and daunorubicin (DNR) on phosphatidylserine (PS) exposure and related procoagulant activity of acute promyelocytic leukemia (APL) cells. METHODS: Mononuclear cell and neutrophil isolated from whole blood of 12 healthy volunteers were used as control group while APL cells obtained from 12 newly diagnosed APL patients at First Affiliated Hospital, Harbin Medical University from March 2007 to February 2009 were used as experimental group. APL cells were treated with 1 umol/L ATO and 1 umol/L DNR for 24 h. PS exposure of APL cells were measured by flow cytometry and confocal microscopy. And the related procoagulant activity was detected by the assays of coagulation time and coagulation factor formation. Lactadherin was used as a probe for PS exposure and anticoagulant on the cells of 12 APL patients. RESULTS: ATO induced a decrease of PS exposure on APL cells by flow cytometry and no staining with lactadherin was observed under confocal microscopy. However, DNR induced the significantly elevated PS exposure and staining green with a rim pattern on membrane of APL cells was obtained. Coagulation time was (180 +/- 25) s and (220 +/- 41) s before and after treatment with ATO, respectively (P < 0.05). The formation of coagulation factors decreased after treatment with ATO (P < 0.05). While coagulation time was (180 +/- 25) s and (80 +/- 20) s before and after treatment with DNR, respectively (P < 0.05). The formation of coagulation factors increased after treatment with DNR (all P < 0.05). Lactadherin inhibited the procoagulant activities of DNR-treated APL cells (all P < 0.05). CONCLUSIONS: Procoagulant activity is positively correlated with the exposed PS of APL cells. ATO and DNR inhibited and enhanced procoagulant activity with decreased and increased PS exposure, respectively. PMID- 22781767 TI - [Regulation of miRNA-15a/-16 expression on the drug resistance of myeloma cells]. AB - OBJECTIVE: To explore the effects and mechanism of bone marrow stromal cells (BMSCs) on the drug resistance of multiple myeloma (MM). METHODS: Fresh untreated MM patient (5 samples) and health donor (5 samples) bone marrow samples were collected from May 2011 to July 2011 at our hospital. Their BMSCs were separated respectively. The supernatant expression of cytokines in BMSCs was detected by enzyme-linked immunosorbent assay (ELISA). Myeloma cells were co-cultured with BMSCs and treated with melphalan or bortezomib. Cell proliferation and miRNA-15a/ 16 expression of myeloma cells were measured in different culture conditions with thiazoyl blue tetrazolium bromide (MTT) assay and quantitative real-time PCR (qRT PCR). miRNA-15a was transfected into myeloma cells. And the miRNA-15a functions on cell cycle and cell apoptosis were detected by flow cytometry. RESULTS: ELISA assay showed that cytokine IL-6 and VEGF were at higher levels in MM-BMSCs than healthy BMSCs ((189 +/- 9) vs (115 +/- 15) pg/ml, (1497 +/- 40) vs (1239 +/- 21) pg/ml, both P < 0.05). The miRNA-15a/-16 expressions of myeloma cells were up regulated after the treatment of melphalan and bortezomib (all P < 0.05). However, the miRNA-15a/-16 up-regulation by melphalan or bortezomib became inhibited when MM cells were co-cultured with MM-BMSCs (melphalan: 4.690 +/- 0.050 vs 34.440 +/- 4.100, 0.760 +/- 0.070 vs 12.030 +/- 1.020, bortezomib: 1.440 +/- 0.230 vs 11.480 +/- 1.488, 0.880 +/- 0.040 vs 3.680 +/- 0.420, all P < 0.05). Furthermore, IL-6 suppressed the expression of miRNA-15a/-16 in a dose and time dependent pattern. The transfection of miRNA-15a led to the arrest of MM cell cycle in G(1)/S phase. CONCLUSIONS: BMSCs suppress the proliferation of myeloma cells and regulate the drug sensitivity of myeloma cells through the inhibited expression of miRNA-15a/-16. IL-6 plays a pivotal role in the occurrence of drug resistance. PMID- 22781768 TI - [Serum level of MMP-2 in early breast cancer and its correlation with circulating tumor cells]. AB - OBJECTIVE: To explore the serum levels of MMP-2 in early breast cancer and its clinical significance and correlation with the circulating tumor cells in the patients. METHODS: The serum levels of MMP-2 in breast fibroadenoma (n = 10) and breast cancer (n = 72) were detected by enzyme-linked immunosorbent assay (ELISA). And CK19 mRNA was measured by quantitative reverse transcription polymerase chain reaction in blood as an index of circulating tumor cells in the patients. RESULTS: The serum level of MMP-2 in breast cancer was significantly higher than that in breast fibroadenoma (12.24 vs 2.21 ug/L, P = 0.003). Subgroup analysis showed that the serum levels of MMP-2 were higher in HER-2 positive patients than those in HER-2 negative ones (16.77 vs 10.02 ug/L, P = 0.022). CK19 mRNA was found in blood samples from 30 cases of breast cancer and the positive rate was 41.7%. However, it was not detected in the patients with breast fibroadenoma. The mean levels of serum MMP-2 were (15.48 +/- 2.02) and (7.16 +/- 1.55) ug/L in CK19 positive and negative patients respectively. Significant difference existed between two groups (P = 0.013). CONCLUSION: The serum level of MMP-2 in early breast cancer is closely correlated with blood micrometastasis. And its high level may be an important contributing factor for the metastasis of breast cancer. PMID- 22781769 TI - [Clinical features and screening of ACVRL1 gene in II hereditary hemorrhagic telangiectasia]. AB - OBJECTIVE: To analyze the clinical features and pathogenic gene of the patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: The clinical features of 3 HHT families were collected. And the patients were diagnosed according to clinical diagnostic analyzed criteria of HHT, the ACVRL1 gene screened and the conservation of mutation protein. RESULTS: Three probands and 1 patient were diagnostic for HHT and 2 patients were suspected. In family I, there was a missense mutation of ACVRL1 gene in c.287A > G on 2 patients, leading to the transferal of amino acids from Asn to Ser at 96(th) place. In family II, there was a missense mutation of c.1271C > T on ACVRL1 in 2 patients, leading to the transfer of amino acids from Pro to Leu at 424(th) place. In family III, there was a deletion mutation of c.147delC on ACVRL1 so as to produce only the former 53 amino acids of ALK1 protein. Through an analysis of multi-species conservation, the mutations were conserved between multiple species. By querying the National Center for Biotechnology Information (NCBI) database, we confirmed that the mutation was not of a single nucleotide polymorphism (SNP). CONCLUSION: The genetic screening of HHT patients may identify their virulence gene. And genetic screening of their offspring is helpful for the early diagnosis and prevention before disease onset. PMID- 22781770 TI - [Fast-track surgery accelerates the recovery of postoperative humoral immune function in elective operation for colorectal carcinoma: a randomized controlled clinical trial]. AB - OBJECTIVE: To explore the effects of fast-track surgery on postoperative humoral immune function in patients undergoing elective colorectal resection. METHODS: Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into fast-track group (n = 35) and conventional care group (n = 35). The clinical parameters and markers of humeral immune function were evaluated in both groups postoperatively. RESULTS: Sixty-two patients finally completed the study, including 32 in the fast-track group and 30 in the conventional care group. There was a significantly faster recovery of postoperative humoral immunity: blood levels of globulin (24.1 +/- 2.4 vs 22.1 +/- 3.3 g/L, P = 0.025), immunoglobulin G (10.79 +/- 2.39 vs 8.66 +/- 2.09 g/L, P = 0.007) and complement 4 (0.24 +/- 0.09 vs 0.17 +/- 0.05 g/L, P = 0.035) at Day 3 postoperation were higher in the fast-track group than in the conventional care group. And there was also a significantly shorter length of postoperative stay (6.0 +/- 1.0 vs 11.7 +/ 3.8 d, P < 0.001) in patients undergoing fast-track rehabilitation. CONCLUSION: Fast-track surgery accelerates the recovery of postoperative humoral immune function in elective surgery for colorectal carcinoma with a shorter length of postoperative hospital stay. PMID- 22781771 TI - [Effects of continuous positive airway pressure upon the un-treatment hour changes of blood glucose level in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes]. AB - OBJECTIVE: To assess the effects of short-term continuous positive airway pressure (CPAP) upon un-treatment hour glucose control via a continuous glucose monitoring system (CGMS) in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes (OWD). METHODS: A total of 23 case of hospitalized OWD were recruited. CGMS was applied for 2 days before and 4 days during CPAP treatment. The treatment hour (6 h, 0:00 - 6:00) and un-treatment hour (14 h, 6:00 - 22:00) glucose level and glucose variability were analyzed. Insulin resistance was assessed with fasting plasma blood glucose (FPG), plasma insulin (FINS) and homeostatic model assessment of insulin resistance index (HOMA-IR). RESULTS: The short-term CPAP treatment corrected sleep-disordered breathing and induced significant decreases of treatment and un-treatment hour glucose level ((7.07 +/- 2.02) mmol/L vs (6.34 +/- 1.57) mmol/L, (8.04 +/- 1.99) mmol/L vs (7.64 +/- 1.81) mmol/L, both P < 0.05). Glucose variability of treatment and un treatment hours significantly decreased after CPAP treatment (0.41 +/- 0.24 vs 0.29 +/- 0.18, 1.02 +/- 0.50 vs 0.78 +/- 0.45, all P < 0.05). Short-term treatment also induced an increase of insulin sensitivity, as indicated by a significant decrease of HOMA-IR (4.02 +/- 2.07 vs 3.08 +/- 1.58, P < 0.05). CONCLUSION: Short-term CPAP treatment in OWD may improve not only insulin resistance but also blood glucose and glucose variability during treatment and un treatment hours. PMID- 22781772 TI - [Delayed massive hemorrhage after pancreaticoduodenectomy]. AB - OBJECTIVE: To summarize our clinical experiences of delayed massive hemorrhage (DMH), a rare but fatal complication, after pancreaticoduodenectomy (PD). METHODS: The clinical data of 14 DMH patients at our medical center were collected and analyzed to evaluate the risk factors and to compare the efficacies of different therapies. RESULTS: A total of 1008 PD patients were treated since April 1993. Fourteen DMHs occurred post-operatively (1.4%). In these cases, 10/14 (71.4%) were complicated with pancreatic fistula. Sentinel bleeding was observed in 10 (71.4%) cases. The clinical manifestations of DMH included simple abdominal hemorrhage (n = 6, 42.9%), alimentary tract hemorrhage (n = 6, 42.9%) and both (n = 3, 21.4%). Shock (n = 2, 14.3%) might also be the initial symptom. Thirteen cases achieved post-therapeutic hemostasis while 1 patient died before re admission. The therapeutic modalities included interventional therapy (n = 8) and surgery (n = 5). According to the therapeutic modalities, the re-bleeding rate, morbidity and final mortality of two groups were 50.0% vs 40.0% (P = 0.83), 75.0% vs 60.0% (P = 0.96) and 50.0% vs 80.0% (P = 0.62) respectively. Five patients survived at the end of treatment. The mortality rate was 71.4%. CONCLUSION: As a rare but fatal complication after PD, DMH is difficult to diagnose and treat. Postoperative pancreatic fistula remains a possible but undetermined risk factor. Sentinel bleeding is of great predicative value for DMH. Regular interventional arteriography is an effective method of improving diagnosis and treatment. Both interventional therapy and surgery may be used to treat DMH. PMID- 22781773 TI - [Expression of proteasome beta5 subunit in human atherosclerotic plaque]. AB - OBJECTIVE: To evaluate the expression of proteasome beta5 subunit in human atherosclerotic plaque. METHODS: The specimens of carotid endarterectomy were collected from 16 carotid stenosis patients. For the case group, they were divided into 2 groups: plaque (group A) and areas adjacent to plaque (group B). And carotid endarterium was obtained from 6 patients undergoing aortic replacement surgery. Relatively normal arterial intima (subclavian artery & innominate artery) was selected as the control group (group C). Content of proteasome beta5 subunit was evaluated by hematoxylin & eosin (HE) staining, immunohistochemistry and Western blot. RESULTS: (1) In patients with diabetes, hyperlipidemia and probable smoking, proteasome beta5 subunit was enhanced in all groups; (2) Proteasome beta5 subunit was demonstrated in both cytoplasm and nucleus of vascular smooth muscle cells, but mainly confined to cytoplasm; (3)The positive expression rate of beta5 was 9/16 in group A, 11/16 in group B and 6/6 in group C. There was significant divergence in the expression of beta5 in different sample sub-groups: group A (atherosclerotic plaque) < group B (areas adjacent to plaque) < group C (control group). CONCLUSION: The expression of beta5 decrease markedly in human atherosclerotic plaques. PMID- 22781774 TI - [Clinical observation of relapsing polychondritis: a report of 23 patients]. AB - OBJECTIVE: To explore the clinical characteristics of relapsing polychondritis (RP) for its early diagnosis and treatment. METHODS: A retrospective analysis was performed for the clinical data and prognoses for 23 RP patients from April 1996 to October 2011 at Departments of Respiratory Medicine, Rheumatism and Otorhinolaryngology, First Affiliated Hospital, Zhengzhou University. RESULTS: Lesion locations included auricle (n = 19), joints (n = 17), nose (n = 14), respiratory tract (n = 10), eyes (n = 6), inner ear (n = 4), costal cartilage (n = 3) and kidney (n = 1). Laboratory examinations revealed elevated erythrocyte sedimentation rate (ESR) (n = 18), elevated C-reactive protein (CRP) (n = 16) and positive rheumatoid factor (n = 2). Laryngeal mucosa was edematous and the vocal cords were paralyzed in the cases with airway involvement under laryngofiberscopy. Tracheal mucosa was highly edematous and tracheal lumen narrowed in the cases examined under bronchofibroscope. Laryngeal mucosa was swollen, glottic chink narrowed, laryngeal cartilage partially absorbed and deformed in the cases examined with neck computed tomography (CT). Tracheal mucosa was thickened, tracheal lumen narrowed and tracheal cartilage was deformed and calcified in the cases on chest CT. Pathological examination on tracheal cartilage showed that cartilage tissue was degenerative and fibrotic. And the proliferation of granulation tissue and the infiltration of inflammatory cells were present around cartilage tissue. Twenty-three RP patients received the therapies of antibiotics, glucocorticosteroid, immunosuppressive agent, tracheotomy or tracheal stent implantation. Two cases died of asphyxia. One case died of myocardial infarct. The symptoms of other 20 cases improved in different degrees. CONCLUSION: The clinical manifestations are diverse in RP patients. The prognoses of patients with airway involvement are worse and may be improved by an early diagnosis and correct treatment. PMID- 22781775 TI - [Expression of interleukin-21 in the lungs of mice with emphysema and its effects on the differentiation of CD4+ T cell]. AB - OBJECTIVE: To evaluate the expression of interleukin (IL)-21 in a cigarette smoke induced mice model of emphysema and explore its effects on the differentiation of CD4(+)T cell. METHODS: Twenty male Balb/c mice were randomly divided into two groups: control group and smoke-exposed group. Morphological changes were evaluated by mean linear intercepts and alveolar destructive index. The proportion of CD4(+)IL-21R(+)T cells in lungs of mice was determined by flow cytometry. And the levels of IL-21 in lungs of mice were analyzed by enzyme linked immunosorbent assay (ELISA). Fresh lung mononuclear cells were isolated from the smoke-exposed group and divided further into two sub-groups: blank sub group and co-culture sub-group. Two sub-groups were cultured in medium with or without IL-21 for 24 h and 48 h. The proportions of Th1 and Th17 cells in cell culture medium were determined by flow cytometry. RESULTS: Mean linear intercepts and alveolar destructive index in the smoke-exposed group ((48.6 +/- 4.8) um and 44.9 +/- 2.8) were significantly higher than the control group ((32.4 +/- 4.0) um and 28.1 +/- 2.1, both P < 0.05). In lungs, the percentage of CD4(+)IL-21R(+)T cells in the smoke-exposed group (4.1% +/- 1.5%) significantly increased than that in the control group (1.4% +/- 0.4%) (P < 0.05). The levels of IL-21 in lung of the smoke-exposed group ((851 +/- 28) ng/L) were higher than those in the control group ((415 +/- 39) ng/L, P < 0.05). In lungs, the levels of IL-21 had positive correlations with mean linear intercepts and alveolar destructive index (r = 0.892 and 0.955, both P < 0.05). The percentages of Th1 and Th17 cells in cell culture medium of the co-culture sub-group for 24 h and 48 h significantly increased versus those in the blank group (all P < 0.05). CONCLUSION: IL-21 may participate in the occurrence and development of emphysema through the induced differentiation of CD4(+)T cells and the promotion of Th1 and Th17-cell responses in lungs. PMID- 22781776 TI - [Study of sequence-dependent in vitro effects of zoledronic acid and paclitaxel upon human nasopharyngeal carcinoma cell line HNE1]. AB - OBJECTIVE: To explore the in vitro effects of anti-proliferation and apoptosis inducing with different sequence regimens of zoledronic acid plus paclitaxel in human nasopharyngeal carcinoma cell line HNE1 so as to explore the optimal sequence regimen of these two drugs and related mechanism. METHODS: The cytotoxic effects of different sequence schemes of zoledronic acid plus paclitaxel on HNE1 cells were detected by methyl-thiazol-tetrazolium (MTT) assay. Annexin V-FITC/PI double staining flow cytometry (FCM) and terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay were used to measure the effects of zoledronic acid plus paclitaxel upon apoptosis. The expressions of mRNA of Bcl-2, Bax, Caspase3 and Caspase9 gene were detected by real-time quantitative-polymerase chain reaction (PCR) and protein was detected by Western blot. RESULTS: All experiment groups enhanced the effect of anti-proliferation by MTT assay (P < 0.05); the treatment of zoledronic acid followed by paclitaxel was superior to the other two regimens (P < 0.05). As detected by FCM, the early apoptotic rate of control group was 2.59% +/- 0.28% and the experiment groups were 13.89% +/- 0.69%, 11.73% +/- 0.54%, 23.97% +/- 0.68%, 10.45% +/- 0.16% and 8.59% +/- 0.74% respectively (P < 0.05). TUNEL assay detected the late apoptosis of HNE1 cells and the experiment groups enhanced the effect of apoptosis-inducing (P < 0.05). The treatment of zoledronic acid followed by paclitaxel was superior to the other regimens (P < 0.05). Such an effect was due to the down-regulation of anti-apoptotic protein Bcl-2 and up-regulations of pro-apoptotic proteins Bax, Caspase3 and Caspase9 at the expression levels of mRNA and protein. There was a greater regulation in the group of zoledronic acid followed by paclitaxel. CONCLUSION: Zoledronic acid can enhance the in vitro effects of anti proliferation and apoptosis-inducing for paclitaxel on HNE1 cell. The treatment of zoledronic acid followed by paclitaxel may be the optimal regimen. Synergistic induction of apoptosis is via the effects of Bcl-2 family and through the mitochondrial pathway. PMID- 22781777 TI - [Epitopic multiple antigen peptide from alpha-fetoprotein elicit antitumor immune response in vitro and ex vivo]. AB - OBJECTIVE: To explore the antitumor effects of multiple antigen peptide (MAP) vaccine from alpha-fetoprotein (AFP) through AFP-specific cytotoxic T lymphocyte (CTL) against hepatoma in vitro and ex vivo. METHODS: Dendritic cells (DC) were generated from human peripheral blood mononuclear cells (PBMC) and HLA-A2.1 transgenic murine bone marrow. The AFP-specific CTL were induced by MAP-loaded DC and the corresponding linear peptides from human AFP. The lysis rate of effectors to hepatoma cells were tested by 4 h (51)Cr release assay. And enzyme-linked immunosorbent spot (ELISPOT) was used to test the interferon (IFN)-gamma release of effector cells. RESULTS: The specific lysis rate of effectors induced by AFP epitopic MAP vaccines to Hep3B cells (AFP(+), HLA-A2.1(+)) at the highest effector/target (E/T) ratio was significantly higher than linear peptide vaccine (73.5% +/- 7.9% vs 45.6% +/- 6.9%, P < 0.01). The effectors induced by AFP epitopic MAP vaccine and linear peptide vaccine could not lysis the AFP-negative PLC/PRF/5 liver cancer cells versus the negative control group at the highest E/T (9.3% +/- 3.9%, 8.1% +/- 2.8% vs 8.3% +/- 2.6%, both P > 0.05). But the effectors induced by AFP epitopic MAP vaccine and linear peptide vaccine could lyse PLC/PRF/5 liver cancer cells transfected with cDNA of AFP versus the negative control group (74.8% +/- 10.5%, 51.4% +/- 12.6% vs 4.2% +/- 1.3%, both P < 0.01). And the specific lysis rate of effectors induced by AFP epitopic MAP vaccines was significantly higher than the corresponding linear peptide vaccine (P < 0.01). Compared with the negative control group, the effectors could not lyse HepG2 liver cancer cells, a HLA-A2.1 negative cell line (both P > 0.05). But the effectors could lyse HepG2 cells transfected with cDNA of HLA-A2.1 (71.8% +/- 8.6%, 46.5% +/- 6.5% vs 4.1% +/- 1.1%, both P < 0.01). And the specific lysis rate of effectors induced by MAP vaccine was significantly higher than the corresponding linear peptide vaccine (P < 0.01). ELISPOT test showed that the capability of enhancing IFN-gamma release of human AFP MAPs was stronger than that of the AFP linear peptides. The spots count of MAP vaccine group ((158 +/- 23) spots/10(5) cells) or linear peptide vaccine group ((78 +/- 12) spots/10(5) cells) were significantly higher than the negative control group ((3 +/- 1) spots/10(5) cells) (all P < 0.01). The spots count of the positive control group ((166 +/- 32) spots/10(5) cells) showed no significant difference with the AFP MAP vaccine group (P > 0.05). And the spots count of MAP vaccine group were significantly higher than the corresponding linear peptide vaccine group ((78 +/- 12) spots/10(5) cells, P < 0.01). CONCLUSIONS: AFP multiple antigen peptides elicit not only more powerful specific anti-tumor immune responses but also stronger non-specific anti-tumor immune activities than their corresponding linear peptides. These findings will provide theoretical rationales for their clinical applications. PMID- 22781778 TI - Hybridization in situ of salivary glands, ovaries, and embryos of vector mosquitoes. AB - Mosquitoes are vectors for a diverse set of pathogens including arboviruses, protozoan parasites and nematodes. Investigation of transcripts and gene regulators that are expressed in tissues in which the mosquito host and pathogen interact, and in organs involved in reproduction are of great interest for strategies to reduce mosquito-borne disease transmission and disrupt egg development. A number of tools have been employed to study and validate the temporal and tissue-specific regulation of gene expression. Here, we describe protocols that have been developed to obtain spatial information, which enhances our understanding of where specific genes are expressed and their products accumulate. The protocol described has been used to validate expression and determine accumulation patterns of transcripts in tissues related to mosquito borne pathogen transmission, such as female salivary glands, as well as subcellular compartments of ovaries and embryos, which relate to mosquito reproduction and development. The following procedures represent an optimized methodology that improves the efficiency of various steps in the protocol without loss of target-specific hybridization signals. Guidelines for RNA probe preparation, dissection of soft tissues and the general procedure for fixation and hybridization are described in Part A, while steps specific for the collection, fixation, pre-hybridization and hybridization of mosquito embryos are detailed in Part B. PMID- 22781779 TI - Changing attitude to mental illness among community mental health volunteers in south-western Nigeria. AB - BACKGROUND: Community-based mental health services may be impaired by stigmatization and social distance towards persons with mental illness. Little is known about the impact of education on the attitude of volunteers for mental health programmes. This study aimed to examine the effect of an educational programme on the attitude of community volunteers towards mental illness. METHODS: Thirty-one volunteers for a community mental health programme completed the Familiarity with Mental Illness Questionnaire and a modified version of the Bogardus Social Distance Scale (Bogardus, 1925) before and after an educational programme. RESULTS: At the end of the educational session, perceived dangerousness was significantly reduced and attitude (social distance) towards persons with mental illness showed significant improvement. CONCLUSION: Attitudes of community volunteers towards persons with mental illness improve with educational programmes. This may lead to improved treatment and care of individuals who are mentally ill. PMID- 22781780 TI - Risk factors for psychological distress in Northern Ireland. AB - BACKGROUND: Stress-related mental ill health and its disorders are considered by the World Health Organization (WHO) to be the new world epidemic and their prevalence rates seem to be increasing worldwide. AIMS: To examine and identify sub-populations at risk for psychological discomfort in Northern Ireland and map the relative impact of potential predictors. METHODS: A sample of 4,638 respondents to the NIHSW-2001 survey was analysed with latent class analysis and latent class factorial analysis. Latent class multinomial logistic regression assessed the impact of a range of predictors on class membership. RESULTS: Five sub-populations were differentiated. All subgroups at risk for anxiety and depression were characterized as being younger and female. Disability and adverse life events were strong predictors of risk. Long-standing illness and housing worries were predictors of medium and high risk membership. The effect of civil unrest was significant only for the medium-risk subgroup; marital status and income did not affect group membership. CONCLUSIONS: Because all five subgroups showed a different probability, but a similar profile of endorsing GHQ-12 items, it could be hypothesized that an underlying continuum dimension of anxiety and depression is present in the Northern Irish population. PMID- 22781782 TI - Effects of a dietary intervention and weight change on vasomotor symptoms in the Women's Health Initiative. AB - OBJECTIVE: The aim of this study was to determine whether a dietary intervention designed to reduce fat intake and increase intake of fruit, vegetables, and whole grains, and weight loss, reduces vasomotor symptoms (VMS; ie, hot flashes or night sweats) in postmenopausal women. METHODS: We included 17,473 postmenopausal US women, ages 50 to 79 years, at baseline who participated in the Women's Health Initiative Dietary Modification trial and were not taking menopausal hormone therapy. Logistic regression was used to evaluate associations. RESULTS: In multivariate-adjusted analyses, with simultaneous adjustment for the intervention and weight change, assignment to the dietary intervention versus the control arm was significantly (odds ratio [OR], 1.14; 95% CI, 1.01-1.28) related to a higher likelihood of symptom elimination among women with VMS at baseline. In addition, women with symptoms at baseline who lost 10 lb or more (OR, 1.23; 95% CI, 1.05 1.46) or lost 10% or more of their baseline body weight (OR, 1.56; 95% CI, 1.21 2.02) between baseline and year 1 were significantly more likely to eliminate VMS compared with those who maintained weight. Upon examining the joint effect of the dietary modification and weight loss, compared with women in the control arm who maintained weight, women who lost substantial weight (>= 10%) as a part of the intervention (OR, 1.89; 95% CI, 1.39-2.57) but not as part of the control arm (OR, 1.40; 95% CI, 0.92-2.13) were significantly more likely to end VMS, although these two groups did not differ significantly from each other. Large weight loss (>22 lb), but not dietary changes, was related to the elimination of moderate/severe VMS. CONCLUSIONS: Weight loss as part of a healthy dietary modification may help eliminate VMS among postmenopausal women. PMID- 22781783 TI - Formononetin reverses established osteopenia in adult ovariectomized rats. AB - OBJECTIVE: Formononetin (Formo) prevents ovariectomy (Ovx)-induced bone loss in rats. However, there are no reports on the curative effects of Formo. The objective of this study was to investigate the ability of Formo in restoring trabecular microarchitecture and promoting new bone formation in osteopenic rats. METHODS: Adult Sprague-Dawley rats were ovariectomized and left for 90 days for osteopenia to develop. After 90 days, Formo (10.0 mg kg d) was given orally for the next 12 weeks to Ovx rats in a therapeutic protocol. Sham-operated, Ovx + vehicle, and Ovx + parathyroid hormone (PTH) groups served as controls. Trabecular microarchitecture, osteoid formation, bone turnover/resorption markers, and bone osteoprotegerin-to-receptor activator for nuclear kappaB ligand ratio were studied. One-way analysis of variance was used to test significance of effects. RESULTS: Formo treatment significantly restored the lost trabecular microarchitecture in the femurs and tibia of osteopenic Ovx rats and promoted new bone formation. Formo was devoid of any uterine estrogenicity. Serum levels of type I collagen N-terminal propeptide, which is a reliable marker of bone formation, were increased in Ovx rats treated with Formo compared with Ovx + vehicle group, and the levels were comparable with those in the sham group. Formo prevented the Ovx-induced increase in bone turnover markers, including serum osteocalcin and urinary type I collagen degradation product. Furthermore, Formo treated Ovx rats had an increased bone osteoprotegerin-to-receptor activator for nuclear kappaB ligand ratio compared with the Ovx + vehicle group. CONCLUSIONS: Daily oral administration of Formo for 12 weeks has a substantial anabolic effect, thus raising the possibility of its use in postmenopausal osteoporosis. PMID- 22781784 TI - The osteoprotective effect of psoralen in ovariectomy-induced osteoporotic rats via stimulating the osteoblastic differentiation from bone mesenchymal stem cells. AB - OBJECTIVE: Psoralea corylifolia extract has been reported to promote bone formation in osteoporotic animals. Psoralen (PSO), a flavonoid glycoside, as the active component of P corylifolia L, is effective in increasing new bone-forming osteoblasts in parietal bone defects. However, the effect and molecular mechanisms of PSO on bone mesenchymal stem cells (bMSCs) in the osteoporotic state are widely unknown. This study was designed to evaluate the osteoprotective effect of PSO in ovariectomy (OVX)-induced rats and to seek possible molecular mechanisms of PSO in bMSCs. METHODS: We observed the osteogenic effect of PSO (3 month treatment) on osteoporotic rat models induced by OVX via testing bone densitometry, histomorphometries, and immunohistochemistry in vivo. Alkaline phosphatase staining and colony-forming unit-fibroblast and colony-forming unit adipocyte assays were performed to evaluate the differentiation potential of bMSCs ex vivo. In addition, the molecular targets of PSO in bMSCs were detected by stem cell microarray analysis of 256 genes and confirmed by real-time reverse transcription-polymerase chain reaction. RESULTS: Micro-CT morphometry analysis showed that PSO significantly improved bone mass indicators including increased trabecular thickness and decreased trabecular space. Meanwhile, PSO elevated the well-known osteogenic marker osteocalcin level in OVX-induced osteoporotic rats. Next, in ex vivo studies, we revealed that PSO facilitated alkaline phosphatase staining and increased the colony-forming unit-fibroblasts. Based on gene expression profile analysis, we screened a set of genes dysregulated in OVX but reversed by PSO treatment. These genes were highly enriched in the Notch signaling pathway, which was documented to play a role in bMSC differentiation. CONCLUSIONS: Our findings show that PSO promotes bone mass in OVX-induced osteoporotic rats. This effect of PSO is highly related to the stimulation of differentiation of bMSCs to osteoblasts. PMID- 22781786 TI - Validation of body adiposity index as a measure of obesity in overweight and obese postmenopausal white women and its comparison with body mass index. AB - OBJECTIVE: The purpose of this study was to evaluate whether the recently developed body adiposity index (BAI) in Mexican American and African American women could be validated in postmenopausal American white women and to determine if it is a better obesity classification measure than body mass index (BMI) is in the latter population. METHODS: Total body percentage adiposity (%adiposity) measured by dual-energy x-ray absorptiometry (DXA) was compared with total body %adiposity predicted by BAI in 187 overweight/obese postmenopausal white women (mean +/- SD %adiposity, 45.9 +/- 4.9% and 38.3 +/- 6.2% for DXA and BAI, respectively). SPSS 19.0 and Medcalc 11.6.1.0 were used to conduct Pearson's correlations (r), paired t test, receiver operating curve, and Lin's concordance coefficient (rhoc) and to create Bland and Altman's limit-of-agreement plot. RESULTS: Pearson's correlation analysis revealed a strong association between DXA %adiposity and BAI (r = 0.78, P < 0.001), DXA %adiposity and BMI (r = 0.75, P < 0.001), and BMI and BAI (r = 0.90, P < 0.001). Bias correction factor was 0.51 between DXA %adiposity and BAI. Paired t test showed a significant mean difference between measurements (P < 0.0001), and the plot showed that BAI underestimated DXA %adiposity by 7.56%. Concordance coefficient (rhoc = 0.39; 95% CI, 0.33-0.46) revealed a poor agreement strength. There was no difference between the area under the curve statistic for BAI and BMI. CONCLUSION: Based on our results, BAI has limitations for use in a clinical setting in overweight/obese postmenopausal white women but may be practical for research applications and eventually developed into an easy method to estimate overweight/obesity in other settings. PMID- 22781787 TI - Assessment of sexual function and related factors in mid-aged sexually active Spanish women with the six-item Female Sex Function Index. AB - OBJECTIVE: The aim of this study was to assess sexual function and related factors (menopause-related quality of life and mood included) in mid-aged Spanish women. METHODS: This was a cross-sectional study in which 179 sexually active women (40-65 y old) completed the six-item Female Sexual Function Index (FSFI-6), the Menopause Rating Scale (MRS), the Hospital Anxiety and Depression Scale (HADS), and a sociodemographic questionnaire containing personal and partner data. RESULTS: Median age was 51 years; 55.3% of the women were naturally postmenopausal, 47.5% had increased body mass index, and 6.7% had hypertension. Currently, 4.5% and 19.6% of the women used hormone therapy and psychotropic drugs, respectively. A total of 87.7% had a stable partner; 1.3% of partners abused alcohol and 8.3% had erectile dysfunction. Of the surveyed women, 36.9% displayed total FSFI-6 scores of 19 or less (lower sexual function); 40.2%, mood morbidity (total HADS scores >=11); and 23.5%, impaired quality of life (severe total MRS scores >=17). Cronbach alpha for the FSFI-6 was 0.91. Total FSFI-6 scores positively correlated with female and partner education and inversely with female age and scores on the MRS and the HADS (total and subscale values). Multiple linear regression analysis found that total FSFI-6 scores positively correlated with partner educational level and inversely (worse sexual function) with female age, partner issues (alcohol abuse and erectile dysfunction), and total HADS and urogenital and somatic MRS scores. CONCLUSIONS: In this mid-aged Spanish sample, as assessed with a short and consistent tool, lower sexual function was related to menopausal and mood symptoms and several women and partner factors. Further research using this instrument is warranted. PMID- 22781788 TI - Hot flushes and night sweats differ in associations with cardiovascular markers in healthy early postmenopausal women. AB - OBJECTIVE: The aim of this study was to evaluate the associations between vasomotor symptoms ([VMS] hot flushes or flashes and night sweats) and markers of cardiovascular risk. METHODS: Healthy postmenopausal women in a randomized controlled trial of progesterone for VMS recorded VMS frequency in the Daily Menopause Diary for 28 days at baseline. Accepted risks for cardiovascular disease were measured: body mass index (BMI), waist circumference (WC), waist-to height ratio (WHtR), blood pressure (BP), endothelial function by venous occlusion plethysmography, fasting lipids, glucose, high-sensitivity C-reactive protein, albumin, and D-dimer. Relationships between risk variables and VMS frequency (24 h, day and night) were assessed by univariate and multivariate robust regressions with adjustment for age and WHtR. RESULTS: Data were available for 145 healthy, nonsmoking women without heart disease, hypertension, or diabetes who were 1 to 11 years past their final menstruation and were aged 43 to 65 years, with a mean (SD) BMI of 25.0 (2.9) kg/m and WC of 79.1 (7.1) cm. Anthropometric variables (BMI, WC, and WHtR) were significantly negatively associated with total (24-h day) VMS frequency and with day VMS but not with night VMS frequency. Systolic BP decreased with greater 24-hour VMS frequency, and both systolic and diastolic BPs were inversely related to day but not night VMS frequency. Albumin was positively associated with night VMS frequency but not with day or 24-hour VMS frequency. Other variables showed little association with VMS frequency. CONCLUSIONS: Hot flushes, but not night sweats, were associated with lower cardiovascular risk factors in these healthy postmenopausal women. Future research should differentiate night sweats from hot flushes. PMID- 22781789 TI - Biomechanical evaluation of different abduction splints for the treatment of congenital hip dysplasia. AB - BACKGROUND: Abduction splints for the treatment of hip dysplasia normally operate on curbing the legs at the hip flexion and abduction. The forces are absorbed in different designs of shoulder straps and thus diverted to the shoulder and the spine. The present study is the first comparing these undesired forces of two spread orthoses and subsequently the transmitted forces to the infant's spine. METHODS: Between March 2009 and October 2009 the hips of 290 infants were investigated by ultrasound within the first 3 days after birth. Thereof 20 infants with a hip dysplasia Graf type IIc, D or IIIa met our inclusion criteria and were investigated with a Tubinger and a Superior abduction splint. Biomechanical evaluation was performed by using a high-sensitive strain gauge sensor applied to the infant's orthoses between pelvic harness and shoulder straps. FINDINGS: The transmitted forces to the infant's shoulders correlated significantly with their body mass (P<0.05). Maximal forces on the shoulder of the infants and subsequently transmitted forces on the spine were significantly higher (P<0.05) with the Tubinger splint (range 7.6N to 32.3N; arithmetic mean M: 13.7N) in comparison to the Superior orthosis (range 0.0N to 3.5N; M: 0.7N). INTERPRETATION: The Superior orthosis works with primary load transmission to the pelvic bone. Using the Tubinger splint the shoulders of the newborn infants are loaded with a maximum of 93.9% of their body mass. This may influence the development of the growing infant's spine. PMID- 22781790 TI - [The impact of HLA high resolution typing mismatching of donor-recipient pairs on outcome of unrelated donor hematopoietic stem cell transplantation]. AB - OBJECTIVE: To study the impact of various human leukocyte antigen (HLA) high resolution typing mismatching of donor-recipient pairs on prognosis of unrelated donor hematopoietic stem cell transplantation. METHODS: 835 donor-recipient pairs of CMDP data from 2005 to 2010 were analyzed retrospectively. HLA-A, B, C, DRB1 and DQB1 typing were performed using SBT, SSOP and SSP methods. The diseases involved in acute myeloid leukemia (AML) (n = 288), acute lymphoid leukemia (ALL) (n = 227), chronic myeloid leukemia (CML) (n = 187), myelodysplastic syndrome (MDS) (n = 52), non-hodgkin's lymphoma(NHL) (n = 25), aplastic anemia(AA) (n = 42) and thalassemia (n = 14). Of 835 donor-recipient pairs, 362 were completely matched, 159 had a mismatch for a single allele, 125 had a mismatch for a single antigen, 95 had mismatched for both single allele and single antigen, 29 were mismatched at double allele, 20 at double antigen, 45 at multiple allele and antigen. The follow-up assessment was completed before March 2011. RESULTS: HLA matched pairs had higher overall survival (OS) than HLA-mismatched pairs (79.83% vs 73.15%), but there was no statistically significant differences (P > 0.05). HLA mismatch for a single allele plus a single antigen was a significantly risk factor for OS, disease free survival (DFS) and transplant-related mortality (TRM). The OS from high to low in different diseases were thalassemia, AA, CML, MDS, AML, NHL, and ALL. OS of HLA locus mismatch were DRB1 (94.4%), DQB1 (83.3%), B (75%), A (74.4%) and C (71.4%), respectively. OS of single allele mismatch at HLA locus from high to low were DRB1, C, A, B and DQB1.HLA-A, B, C locus mismatch were statistically significantly associated with lower OS and grade II-IV acute GVHD compared with HLA-matched pairs (P < 0.05). The donor-recipient pairs with HLA-B*15:01/B*15:05, DRB1*12:01/DRB1*12:02, C*04:01/C*03:04, DQB1*03:02/DQB1*03:03 alleles mismatch were given priority. But the donor recipient pairs with HLA-B*39:01/B*39:05, C*15:02/C*14:02, C*08:01/C*03:04, C*07:02/C*15:02 alleles mismatch were risk factors for influence of OS and aGVHD. CONCLUSION: The high resolution typing for HLA-A, B, C, DRB1, DQB1 can be identified nonpermissive mismatch, which is beneficial for the selection of a suitable donor improves survival on unrelated donor HSCT. PMID- 22781791 TI - [Effects of the mobilization with AMD3100, granulocyte-colony-stimulating factor (G-CSF) alone and in combination on the immunological function of the lymphocytes in mice]. AB - OBJECTIVE: To investigate the impact of the mobilization with the antagonist of the stromal cell-derived factor receptor CXCR4 (AMD3100) (plerixafor), granulocyte-colony-stimulating factor (G-CSF) alone and in combination on the proliferation and cytotoxic functions of the murine splenic lymphocytes. METHODS: C57BL/6(H-2(b)) mice, as donors, were mobilized by, AMD3100, G-CSF alone or in combination (n = 10 mice in each group), and phosphate buffered saline (PBS). Then, the proliferation capacity of murine lymphocytes either in response to the phytohemagglutinin (PHA) stimulation or the mixed lymphocytes reaction (MLR) with allo-lymphocytes from the BALB/C(H-2(d)) mice were detected by CCK-8 method. The cytotoxic capacity of murine lymphocytes on Yac-1 tumor cells was examined by LDH assay. RESULTS: The proliferation capacity and the responsiveness to alloantigen of the lymphocytes derived from the mice spleen mobilized by AMD3100, G-CSF alone or in combination were significantly lower than those by PBS control (P < 0.05), and those combination of AMD 3100 and G-CSF group were significantly lower than in other groups(P < 0.05). At the effector-target ration of 40:1, the cytotoxic capacity of murine lymphocytes in above mobilization groups was lower than in control group, but no statistically significant difference (P > 0.05). CONCLUSION: Both the proliferation capacity and the responsiveness to alloantigen of the murine lymphocytes decreases significantly after the mobilization with AMD3100, G-CSF alone or in combination, whereas no significant alternations are demonstrated on the cytotoxic capacity of murine lymphocytes. Further studies are needed to clarify the underlying mechanisms. PMID- 22781792 TI - [Clinical study on platelet engraftment by thrombopoietin in patients with hematological malignancies after allogeneic hematopoietic stem cell transplantation]. AB - OBJECTIVE: To evaluate the efficacy and safety of thrombopoietin (TPO) on platelet engraftment in hematological malignancies patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: One hundred and twenty patients were enrolled in a multicenter, open-label, randomized, controlled clinical trial, and were randomized into 4 treatment groups following allo-HSCT. Group A was the control arm without TPO, while group B, C and D were trial arms with received 300 U*kg(-1)*d(-1) of TPO starting from day +1, +4 and +7, respectively. A total of 89 cases were evaluated, of which 22 cases in group A, 23 in group B, 20 in group C and 24 in group D. Efficacy evaluation (the time of platelet engraftment, the number of platelet transfusion) and safety evaluation ?[adverse events, routine blood tests, liver and renal function, coagulation function and occurrence of graft-versus-host disease (GVHD)?] were observed. RESULTS: The median platelet engraftment time in experimental groups (groups B, C and D) were on day (13.17 +/- 2.89), day (12.15 +/- 2.08), day (12.33 +/- 1.76), respectively, and that in control group was on day (14.82 +/- 5.05). There was statistically significant difference between two groups (P = 0.029), There were no statistically significant difference in the average amount of platelet transfusion, platelet engraftment time, and platelet nadir value among the 3 experimental groups. No significant adverse events were observed in experimental groups. CONCLUSIONS: TPO administration following allo-HSCT for patients with hematologic malignancies appears to shorten platelet engraftment time. TPO given starting from day +7 is effective and safe. PMID- 22781793 TI - [ITF-2357 on inhibition myeloid leukemic cell lines cells proliferation in vitro and its mechanism]. AB - OBJECTIVE: To explore the effect of ITF2357, a novel histone deacetylase (HDAC) inhibitor, on the growth, differentiation and apoptosis of acute myeloid leukemic (AML) cells and its mechanism. METHODS: AML cell lines kasumi-1 cells as a model for AML1-ETO positive, and THP1 cells for AML1-ETO negative, the leukemic cells proliferation was analyzed by MTT assay, expression of myeloid-specific differentiation antigen and cell cycle by flow cytometry, cell apoptosis by annexin V staining and flow cytometry. AML1-ETO, acetyl-histone, and caspase protein was analyzed by Western blot. RESULTS: 0.5 umol/L ITF2357 treatment significantly inhibited kasumi-1 cells proliferation, with the 48 h half inhibitory concentration (IC(50)) of 0.1 umol/L. The initial inhibitory concentration of THP1 cell line was 5 umol/L. ITF 2357 induced apoptosis of kasumi-1 cells in a time- and dose-dependent manner. A dose-dependent increase in early apoptosis occurred at 24 hours treatment and in late apoptosis at 48 hours treatment by ITF2357. Early apoptosis cells increased from (1.44 +/- 1.52)% to (24.51 +/- 5.79)%. Late apoptosis cells increased from (2.37 +/- 2.8)% to (63.66 +/- 1.56)%. ITF2357 induced AML1-ETO degradation by caspase-dependent pathway. 0.25 umol/L ITF2357 induced a time- and dose-dependent increase in expression of myeloid cell surface protein CD13 and CD15. 5 umol/L ITF2357 blocked the cells at G(0)/G(1) phase, G(0)/G(1) cells increased from (39.69 +/- 6.56)% to (79.2 +/- 6.51)% and s-phase cells declined from (60.12 +/- 3.29)% to (18.97 +/- 6.62)%. Kasumi-1 cells incubated with 0.5 umol/L of ITF2357, AML1-ETO protein began to decrease at 24 hours and could hardly be detected at 96 hours. ITF2357 induced AML1/ETO degradation through a caspase-dependent mechanism. At the same time, acetylated H3 and H4 increased. CONCLUSION: Low-dose HDAC inhibitor ITF2357 can effectively inhibit the AML cells proliferation, especially for AML1-ETO positive AML cells. It inhibits Kasumi-1 cells proliferation degradation of AML1-ETO protein expression, blocks the cells at G(0)/G(1) phase, and induces apoptosis and differentiation of the cells. PMID- 22781794 TI - [Enrichment analysis of Fanconi anemia gene expression profiles in cancer related genesets]. AB - OBJECTIVE: To investigate the underlying tumor susceptibility mechanisms and reasons for the high risk of cancer in Fanconi anemia (FA). METHODS: Gene Set Enrichment Analysis (GSEA) was performed to compare gene expression profiles between 21 FA patients' bone marrow (BM) mononuclear cell (BMNC) and 11 normal controls in cancer related gene sets from NCBI GEO database, then core enriched genes were identified by further investigation. Through enrichment analyzing biological processes of gene ontology sets and structural genomic gene sets between FA expression profiles and control, more details related with its tumor susceptibility had been revealed. RESULTS: Compared with normal control, gene expression in FA group had significant been enriched in resistance to Bcl-2 inhibitor gene set, fibroblast growth factors signalling pathways, insulin and insulin-like growth factors (IGF) signalling pathways induced cancer genesis gene sets. The high level of D4S234E, SST, FGFs, IGFs, FGFRs and IGFBP expression provided an initiate environment for tumorgenesis and drug resistance. There were significant differences in biogenesis extracellular molecules and cytomembrane structure organizations between FA and control. Genes with promoter regions around transcription start sites containing either motif RRCAGGTGNCV or CCTNTMAGA were enriched and those former genes match annotation for tumorgenic transcription factor 3 (TCF3). CONCLUSIONS: The high tumor susceptibility of FA patients may be closely related with the dramatic changes in cancer related growth factors and hormones environment. This study provides new insights into tumor susceptibility mechanism in FA patients. PMID- 22781795 TI - [A case of idiopathic eosinophilic syndrome complicated with multiple arterial and venous thrombosis]. PMID- 22781796 TI - [Analysis of clinical features and prognosis of primary myelodysplastic syndromes with myelofibrosis patients]. AB - OBJECTIVE: To analyze the clinical features and prognosis of the primary myelodysplastic syndrome with myelofibrosis (MDS-MF) patients and to improve the cognition of MDS-MF. METHODS: Four hundred and sixty-six primary MDS patients with bone marrow (BM) biopsy were divided into two groups according to whether BM associated with fibrosis, the clinical features and prognosis of the two groups were analyzed retrospectively. RESULTS: 167 (35.8%) MDS cases revealed myelofibrosis, of which MF-1 123 cases (26.4%), MF-2 40 cases (8.6%), MF-3 4 cases (0.9%). The proportion of hepatosplenomegaly in MDS-MF group was significantly higher than in MDS without MF group, the difference had statistical significance (P = 0.031). The proliferation of BM biopsy in MDS-MF group was significantly more active than in MDS without MF group. The number of blasts, megakaryocytes and abnormal megakaryocytes in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P < 0.05). Among the 345 patients who had available results of cytogenetic analysis, 121 cases were MDS-MF patients, the proportion of middle and high-risk prognostic group according to IPSS karyotype prognosis groups in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P = 0.047). The median survival was 17 (1 - 60) months in MDS-MF group, and was 32 (1 - 62) months in MDS without MF group. The difference had statistical significance (P = 0.001). Myelofibrosis had independent prognostic significance by multi-variable analysis (P = 0.019). CONCLUSION: The myelofibrosis in MDS is main the proliferation of reticular fiber. The proliferation of reticular fiber is closely related with the number of blast cells, the proliferation and developmental abnormalities of megakaryocytes and the karyotype. The prognosis of MDS-MF patients is poor. PMID- 22781797 TI - [The effect of retrovirus-mediated HO-1 gene on chronic myeloid leukemia resistance cell K562/A02 apoptosis induced by nilotinib]. AB - OBJECTIVE: To investigate the effect of retrovirus mediated heme oxygenase (HO)-1 gene on chronic myeloid leukemia (CML) resistance cell apoptosis induced by nilotinib (AMN107). METHODS: High titer viral particles of pQCXIP-EGFP-HO-1 were prepared, and K562/A02 cells stably transfected with HO-1 gene was established. The expression of HO-1 in K562/A02 cells was detected by RT-PCR. After treated with AMN107 for 24 h, HO-1 mRNA and protein expression by RT-PCR and Western blot, respectively; Cell proliferation by MTT assay; bcr-abl fusion gene by RQ PCR, and the apoptosis and cell cycle by flow cytometry. RESULTS: Recombinant retrovirus vector was constructed successfully and K562/A02/HO-1 cells were successfully set up. The expression of HO-1 in K562/A02 cells was expressed clearly. After three groups cells treated with AMN107 for 24 h, the expression of HO-1 mRNA and protein was significantly higher in gene-transfected group than in either empty vector or no-transfected group. The difference was statistically significant (P < 0.05). The cell proliferation ofs was inhibited, but the cell viability was significantly higher in gene-transfected group than in other two groups. The difference was statistically significant(P < 0.05); After treated with 10 umol/L AMN107 for 24 h, the CT values of bcr-abl fusion gene were (18.15 +/- 0.18) in K562/A02/HO-1 group, being significantly higher than that in K562/A02/LXSN (20.32 +/- 0.20) and K562/A02 (20.51 +/- 0.21) group, the difference was statistically significant (P < 0.05); the apoptosis rate were (17.26 +/- 0.23)%, (39.47 +/- 0.17)%, and (41.84 +/- 0.09)%, respectively in three groups, and were (3.74 +/- 0.03)%, (5.91 +/- 0.08)% in K563/A02/HO-1 untreated with drug and K562/A02 untreated with drug group. The number of G(0)/G(1) phase and S phase cells markedly decreased. The cells were arrested in G(2)/M phase. But cell cycle in gene-transfected group did not change significantly. CONCLUSION: AMN107 inhibits proliferation of CML resistance cells and induces cell apoptosis. HO-1 gene can protect CML resistance cells to apoptosis. There was a relationship between HO-1 gene and the growth of CML resistance cells. PMID- 22781798 TI - [Clinicopathologic analysis of nodal marginal zone B cell lymphoma]. AB - OBJECTIVE: To investigate the clinicopathologic features of primary nodal marginal zone B-cell lymphoma (NMZL). METHODS: Hematoxylin-Eosin staining and immunohistochemistry were used to evaluate the histological and immunophenotypic characteristics of lymph node (LN) tissue in 22 NMZL cases. Additionally, interphase fluorescence in-situ hybridization (FISH) was carried out to detect the presence of t(11;18) (q21;q21)/API2-MALT1 and/or t(14;18)(q32;q21)/IGH-MALT1 in 9 cases. RESULTS: The median age of the 22 patients was 62 (16 - 77) ys. The male-to-female ratio was 1.2:1. All patients exhibited asymptomatic lymphadenopathy with the cervical region as the most often site to be involved (n = 11), followed by axillary (n = 9), inguinal (n = 7), submandibular (n = 6), mediastinal (n = 4), supraclavicular (n = 2) and retroperitoneal lymph nodes (n = 1). The Ann Arbor stages were I/II in 13 (59%) cases and III/IV in 9 (41%). Immunohistochemical study showed a consistently strong expression of CD20 and an absence in the expression of CD3epsilon, CD10, CD21, CD23, CyclinD1 and BCL6 by the tumor cells in all the cases. Frequency of expression of CD5 and BCL2 were 39% (7/18) and 30% (3/14) respectively. Among the 9 cases performed with FISH, 2 cases harbored t(14;18)and another 1 case positive for t(11;18) and t(14;18). Complete follow-up data were available for 13 cases. The follow-up time was 6 to 44 months. 3 of them died. 3-year cumulative survival rate was 67%. CONCLUSIONS: NMZL patients are often elderly, which mainly present with multiple lymphadenopathy, rare involvement of extranodal organ and early stage. The diagnosis must be based on a combination of clinicopathologic features, especially those patients detected t(11;18) and/or t(14;18). PMID- 22781799 TI - [The effects of JARID1B siRNA on proliferation and apoptosis in HL-60 cell]. AB - OBJECTIVE: To study the effect of small interfering RNA(siRNA) targeting JARID1B gene on the proliferation and apoptosis in HL-60 acute promyelocytic leukemia cell line, and to explore its mechanisms. METHODS: The JARID1B siRNA was transfected into HL-60 cells using Lipofectamine(TM) 2000(Lipo) vector. The proliferation inhibition by siRNA targeting JARID1B was detected by MTT, cells apoptosis by flow cytometry, the mRNA expression of JARID1B by RT-PCR, the protein expression of JARID1B, Bcl-2, procaspase-9, procaspase-3, c-myc and P27 and histone methylated H3K4 by Western blot. RESULTS: siRNA targeting JARID1B upregulated histone methylated H3K4 level, inhibited the proliferation of HL-60 cells, and induced the cells apoptosis. After transfection of siRNA targeting JARID1B at 0, 30, 60, 120 nmmol/L for 24 hours, the apoptotic rate were (11.0 +/- 3.6)%, (35.2 +/- 5.1)%, (52.7 +/- 3.8)%, and (62.0 +/- 5.7)% respectively (F = 70.27, P < 0.01). The protein expression of P27 was upregulated, and Bcl-2, procaspase-9, procaspase-3, c-myc was down regulated. CONCLUSIONS: JARID1B siRNA upregulates histone methylated H3K4. It reduces HL-60 cells proliferation and apoptosis by up regulating the p27 expression and down regulating the Bcl-2, procaspase-9, procaspase-3, c-myc expression. It might be a new therapeutic targeting for human leukemia. PMID- 22781800 TI - [Analysis of IDH1 and IDH2 mutations in patients with acute myeloid leukemia]. AB - OBJECTIVE: To explore the prevalence of IDH gene (IDH1 and IDH2) mutations, types of mutations in patients with acute myeloid leukemia (AML), correlation with the internal tandem duplication(ITD) mutation of FLT3 gene, NPM1 gene mutation and some clinical characteristics. METHODS: The mutations of IDH1 and IDH2 gene at exon 4, NPM1 gene at exon 12 and FLT3-ITD at exon 14 and 15 in 163 newly diagnosed AML patients were detected by PCR amplification followed by direct sequencing of genomic DNA. RESULTS: (1) IDH mutations were found in 25 patients (25/163), and all were heterozygous, of which IDH1 in 7 patients (4.29%) and IDH2 in 18 (11.04%). A total of 4 types of IDH1 mutations were identified (c.395G->A, p.R132H, n = 4; c.394C->A, p.R132S, n = 1; c.394C->G, p.R132G, n = 1; c.315C->T, n = 1). The IDH1 mutation caused substitutions of residue R132 except for one (c.315C->T). All IDH2 mutations caused changes of R140 (c.419G->A, p.R140Q, n = 18). The incidence of IDH2 mutation was significantly higher than that of IDH1 mutation (11.0% v 4.3%, P = 0.022). Both IDH1 and IDH2 mutation were detected in one patient, while IDH1 was synonymous substitution (c.315C->T). IDH-mutated cases showed a significantly higher frequency of concurrent FLT3-ITD mutation compared with wildtype cases (34.6% vs 11.9%, P = 0.003), so did IDH mutations concurrent NPM1 mutation vs NPM1 wildtype (28.1% vs 12.7%, P = 0.033), of which the frequency of concurrent NPM1 and FLT-ITD mutations cases with the IDH mutation was significantly higher than that of NPM1 and FLT-ITD negative (45.5% vs 11.7%, P = 0.002). IDH mutation incidence was significantly higher in normal karyotype cases than in abnormal ones (20.5% vs 5.8%, P = 0.020). Patients with IDH mutations were significantly older than wildtype patients(P < 0.001), whereas, there were no statistically significant differences in gender, peripheral blood (PB) count at diagnosis between two groups. CONCLUSIONS: The incidence of IDH mutation is higher in patients with de novo AMLs, of which IDH2 mutation more frequently, and the patients associated with older age, normal karyotype at diagnosis. IDH mutation has a strong association with NPM1 and FLT3 ITD mutations, suggesting that IDH mutation has synergistic effect with the latter gene on leukemogenesis. PMID- 22781801 TI - [The effect of apoptosis induced by IL-21 in SUDHL-4 cell line and its mechanism]. AB - OBJECTIVE: To investigate the apoptosis effect of diffuse large B-cell lymphoma cell line (DLBCL) SUDHL-4 induced by IL-21 and its related mechanism. METHODS: SUDHL-4 cells were treated with IL-21 at different concentration (1000 ng/ml, 100 ng/ml, 10 ng/ml, 1 ng/ml) for 24 h, 48 h, 72 h, respectively. The inhibitory rate of cell proliferation was detected by CCK-8 assay. The cell growth curves were drawn and half inhibitory concentration (IC(50)) values were calculated. The cell apoptosis were detected by flow cytometry (FCM), the expression of the caspase-9, caspase-3, cleaved caspase-3, Bcl-2, Bcl-XL, Bid, Bax and c-myc protein in SUDHL 4 cells treated with IL-21 by western blot, the mRNA expression of Bcl-2, Bcl-XL, Bid, Bax, c-myc by Survivin gene with RT-PCR. RESULTS: IL-21 markedly inhibited SUDHL-4 cell growth in a time- and dose-dependent manner. The 48 hIC(50) was 140.9ng/ml; The FCM showed that the apoptosis proportion of SUDHL-4 cells treated with 100 ng/ml of IL-21 apoptosis (AnnexinV-FITC(+) positive cells) gradually increased (48 h: 19.7 +/- 2.3%). The protein expression of caspase-9, caspase-3, Bcl-2 and Bcl-XL decreased in a time-dependent manner. The Bax and c-myc protein markedly increased, but the Bid protein level did not change. IL-21 up regulated c-myc and Bax gene expression, however down regulated Bcl-2 and BCL-XL gene expression, but the gene expression of Bid and Survivin hadn't been changed significantly. CONCLUSIONS: IL-21 can inhibit proliferation and induce apoptosis of SUDHL-4 cell. The mechanism may involve in endogenous mitochondrial pathway mediated by the c-myc and the Bcl-2 genes. PMID- 22781802 TI - [Clinical characteristics and rehabilitation treatment of iliopsoas hemorrage in 41 patients with hemophilia]. AB - OBJECTIVE: To analyze the clinical characteristics and effects of rehabilitation treatment on hemophiliacs with iliopsoas hemorrage. METHODS: The hemophilia patients with iliopsoas bleeding treated in Peking Union Medical College Hospital between January 2006 to December 2010 were enrolled. The clinical characteristics including symptoms, signs, complications, and rehabilitation treatment were analyzed retrospectively. RESULTS: All of the forty-one hemophiliacs with iliopsoas bleeding were male, 20 cases wee the left bleeding, 18 the right, and 3 the bilateral. The median median age was 18 (6 - 61) years old(y). The median age of the iliopsoas bleeding for the first time was 17 (6 - 20) y. 34 patients accompanied with femoral nerve injury, 19 of them had secondary knee bleeding on the same side. 20 patents had quadriceps atrophy. Pelvic pseudotumor developed in 2 patients and permanent abnormal posture in 2 patients. The main finding of the ultrasound image was low-echo mass in iliopsoas muscles or inguinal region. 34 patients received rehabilitation therapy for 8 - 12 weeks under the support of factor replacement, complete hematomas absorption in 33 of them, with hip range of motion recovering back to baseline. 27 of 32 (84.4%) cases with femoral nerve injury got quadriceps strength above 4/5 grade, 20 cases of femoral nerve injury (62.5%) still had numbness on front of their thigh after treatment. CONCLUSIONS: In this cohort of iliopsoas bleeding, most of the patients are adolescent. High prevalence of the femoral nerve injury and the secondary knee bleeding are found. Rehabilitation treatment under the support of factor replacement is safe and effective on hematoma absorption and neurological function recovery. PMID- 22781803 TI - [Clinical analysis of recombinant activated factor VIIa for 18 patients with severe bleeding]. AB - OBJECTIVE: To find a kind of quick and effective haemostasis to decrease the mortality of severe bleeding. METHODS: 18 severe bleeding patients with different cause received recombinant activated factor VIIa (rFVIIa) were analyzed retrospectively. RESULTS: Of total 18 cases with severe bleeding, 13 cases cured, 3 cases were effective, 2 cases ineffective. The total clinical effective rate is 88.89%. After using rFVIIa, the PT, APTT and fibrinogen level of 6 DIC patients returned to normal within 12 hours; 13 patients whose the amount of bleeding can be evaluated stopped bleeding quickly. The fastest onset time was 10 min. CONCLUSION: rFVIIa can stanch severe bleeding for a variety of reasons rapidly and effectively, including coagulopathy, thrombocytopenia, and obstetric hemorrhage. Application of rFVIIa may decrease mortality, when conventional treatment is not valid. PMID- 22781805 TI - [The role of serum neuron specific enolase activity in the prognosis of onset multiple myeloma]. PMID- 22781804 TI - [Experimental study of up-regulating PTEN gene on increasing the chemosensitivity in K562/ADM cells]. AB - OBJECTIVE: To investigate the mechanism of decreasing the K562/ADM cells chemosensitivity by up-regulating expression of PTEN gene. METHODS: K562/ADM cells were transient transfected with pGFP-PTEN or vector. The level of PTEN in K562/ADM cells was assayed by Western blot and RT-PCR. Cell viability on K562/ADM was determined by MTT assay. Cell apoptosis by flow cytometry. Activity of caspase-3 by Caspase Colorimetric Assay Kit. The proteins expression of LC3-I/II, Beclin1, p-Akt, p-p70S6K by Western blot. The autophagic vacuoles by MDC stain and Electron microscopy. RESULTS: (1) The mRNA and protein levels of PTEN in K562/ADM cells transfected with pGFP-PTEN were significantly increased compared with the control (untreated and transfected with empty vector). (2) Enhanced expression of PTEN by gene transfection resulted in a reversal of resistance to ADM. Compared with empty vector group, cell viability decreased from (94.07 +/- 2.6)% to (53.83 +/- 4.2)%, the cell apoptotic rate increased from (11.89 +/- 1.7)% to (43.69 +/- 2.3)%, meanwhile, pretreated with caspase-3 inhibitor (Z-DEVE FMK) didn't completely inhibit the cytotoxicity of ADM to K562/ADM cells. (3) After treated with ADM for 12 and 24 h, the activities of caspase-3 in PTEN transfected K562/ADM cells increased compared with those in pGFP-transfected K562/ADM cells ?[(2.27 +/- 0.13) vs (1.19 +/- 0.14)?] at 12h, ?[(3.15 +/- 0.08) vs (1.48 +/- 0.05)?] at 24 h (P < 0.05). (4) The protein levels of LC3-II and Beclin1 in K562/ADM cells transfected with pGFP-PTEN were increased by 83% and 18% respectively, and the protein levels of p-Akt and p-p70S6K were declined by 96% and 87% respectively, compared with those in K562/ADM cells transfected with pGFP plasmid. (5) The upregulation of PTEN in K562/ADM cells improved the number of autophagic vacuoles compared with the empty vector group. CONCLUSION: The upregulation of PTEN expression increases the chemosensitivity of K562/ADM to ADM, which may related with the inhibition of PI3K/AKT/mTOR pathway induced by PTEN gene transfection. PMID- 22781806 TI - [Clinical analysis of diagnosis, treatment and bleeding pattern of 129 moderate and severe preschool hemophiliacs]. PMID- 22781808 TI - [Advances in autoimmune lymphoproliferative syndrome and its related disorders]. PMID- 22781807 TI - [Clinical observation of caffeic acid tablets on cytopenia in patients with newly diagnosed acute leukemia during chemotherapy]. PMID- 22781809 TI - [Advances in new clinical application of recombinant human granulocyte-macrophage colony-stimulating factor]. PMID- 22781810 TI - [A report of five cases of Niemann-Pick Disease from four generations of one family]. PMID- 22781811 TI - A novel aptasensor for the detection of adenosine in cancer cells by electrochemiluminescence of nitrogen doped TiO2 nanotubes. AB - The highly enhanced electrochemiluminescence from a nitrogen doped TiO(2) nanotube array has been reported for the first time, and successfully applied to develop an ultrasensitive ECL aptasensor for the detection of adenosine in cancer cells. PMID- 22781812 TI - Primary motor cortex involvement in initial learning during visuomotor adaptation. AB - Human motor behaviour is continually modified on the basis of errors between desired and actual movement outcomes. It is emerging that the role played by the primary motor cortex (M1) in this process is contingent upon a variety of factors, including the nature of the task being performed, and the stage of learning. Here we used repetitive TMS to test the hypothesis that M1 is intimately involved in the initial phase of sensorimotor adaptation. Inhibitory theta burst stimulation was applied to M1 prior to a task requiring modification of torques generated about the elbow/forearm complex in response to rotations of a visual feedback display. Participants were first exposed to a 30 degrees clockwise (CW) rotation (Block A), then a 60 degrees counterclockwise rotation (Block B), followed immediately by a second block of 30 degrees CW rotation (A2). In the STIM condition, participants received 20s of continuous theta burst stimulation (cTBS) prior to the initial A Block. In the conventional (CON) condition, no stimulation was applied. The overt characteristics of performance in the two conditions were essentially equivalent with respect to the errors exhibited upon exposure to a new variant of the task. There were however, profound differences between the conditions in the latency of response preparation, and the excitability of corticospinal projections from M1, which accompanied phases of de-adaptation and re-adaptation (during Blocks B and A2). Upon subsequent exposure to the A rotation 24h later, the rate of re-adaptation was lower in the stimulation condition than that present in the conventional condition. These results support the assertion that primary motor cortex assumes a key role in a network that mediates adaptation to visuomotor perturbation, and emphasise that it is engaged functionally during the early phase of learning. PMID- 22781813 TI - Forms of confabulation: dissociations and associations. AB - Confabulation denotes the emergence of memories of experiences and events which never took place. Whether there are distinct forms with distinct mechanisms is still debated. In this study, we explored 4 forms of confabulation and their mechanisms in 29 amnesic patients. Patients performed tests of explicit memory, executive functions, and two test of orbitofrontal reality filtering (memory selection and extinction capacity in a reversal learning task) previously shown to be strongly associated with confabulations that patients act upon and disorientation. Results indicated the following associations: (1) Intrusions in a verbal memory test (simple provoked confabulations) dissociated from all other forms of confabulation and were not associated with any specific cognitive measure. (2) Momentary confabulations, defined as confabulatory responses to questions and measured with a confabulation questionnaire, were associated with impaired mental flexibility, a tendency to fill gaps in memory, and with one measure of reality filtering. Momentary confabulations, therefore, may emanate from diverse causes. (3) Behaviourally spontaneous confabulation, characterized by confabulations that the patients act upon and disorientation, was strongly associated with failure in the two reality filtering tasks. Behaviourally spontaneous confabulation may be seen as a specific instance of momentary confabulations with a distinct mechanism. (4) A patient producing fantastic confabulations with nonsensical, illogical content had wide-spread cognitive dysfunction and failed in the reality filtering tasks. The results support the presence of truly or partially dissociable types of confabulation with different mechanisms. PMID- 22781815 TI - IP(3) receptors, stress and apoptosis. AB - Inositol 1,4,5-trisphosphate (IP3) receptors are intracellular calcium channels that are able to release calcium from intracellular stores upon activation by IP3 and modulation by calcium. IP3 receptors are involved in variety of processes during physiological, but also in the pathophysiological states. Unraveling their regulation and function, especially under the pathological situations can result in a development of new therapeutic strategies based on the IP3 receptor's activation and/or blocking. To the stimuli that can modulate IP3 receptors belong several stress factors (e.g. immobilization stress, oxidative stress and hypoxia) and also apoptosis. Depending on the length and strength of the stress stimulus, expression of IP3 receptors can be increased, or decreased. Therefore, in this minireview modulation of IP3 receptors by some stressors is discussed. Since it was already shown that strong hypoxia might lead to the apoptosis induction, special focus will be given to the hypoxic stress and induction of apoptosis. PMID- 22781816 TI - Advances in patch clamp technique: towards higher quality and quantity. AB - The patch clamp technique, developed in late 1970s, started a new period of experimental cardiac electrophysiology enabling measurement of ionic currents on isolated cardiomyocytes down to the level of single channels. Since that time, the technique has been substantially improved by development of several upgraded modifications providing so far unavailable data (e.g. action potential clamp, dynamic clamp, high-resolution scanning patch clamp), or facilitating the patch clamp technique by increasing its efficiency (planar patch clamp, automated patch clamp). The current review summarizes the leading new patch clamp based techniques used in cardiac cellular electrophysiology, their principles and prominent related papers. PMID- 22781814 TI - Bimanual force control strategies in chronic stroke: finger extension versus power grip. AB - Stroke leads to motor asymmetries in the flexor and extensor muscles of the hand. Typically, the strength deficits in the extensors are greater than the flexors. The impact of differential motor abilities of these muscle groups on the execution of bimanual force control tasks in individuals with stroke is unknown. The primary purpose of this study was to determine the influence of task constraints on visually guided bimanual force control in chronic stroke. Stroke survivors and age-matched individuals performed bimanual isometric contractions for 20s to match target submaximal force levels. Online visual feedback of the total force (sum of the forces produced by both hands) was provided. The task constraints were manipulated by (a) finger extension, and (b) finger flexion (power grip). Force asymmetry was indexed by the proportion of force contributed by the paretic hand to the total force. The stroke group demonstrated task specific asymmetry in bimanual force control. Specifically, the paretic hand contributed less force than the non-paretic hand in finger extension whereas this relationship was reversed in power grip. Importantly, regardless of the nature of the task, reduction in motor impairments was associated with increased symmetry and coordination in bimanual tasks. Further, bimanual submaximal grip force control revealed asymmetry and coordination deficits that are not identified by investigating bimanual maximal force production alone. The motor control strategy adopted to optimize performance on bimanual tasks revealed the altered force production of the paretic hand due to the combined effect of extensor weakness and enhanced flexor bias following stroke. Bimanual asymmetries in stroke survivors highlight the need for identifying and treating the task-specific impairments for maximizing motor recovery post stroke. PMID- 22781817 TI - Morphological and functional characteristics of models of experimental myocardial injury induced by isoproterenol. AB - The animal models of myocardial injury induced by systemic beta-adrenergic receptor agonist administration represent an experimental approach of persisting interest. These models were found useful especially for studies of structural and functional adaptation of myocardium during the progression of cardiac adaptive response towards maladaptive hypertrophy and insufficiency. The pathological alterations induced by isoproterenol (ISO) do not develop evenly. The ISO models may contribute effectively to understanding of pathologies in signal transduction, energetics, excitability and contractility that may contribute concomitantly to cardiac dysfunction and heart failure. In this minireview we focused on the alterations in general characteristics and heart function as well as on the morphological changes of cardiomyocytes developed during ISO administration. The morphological alterations within the cellular macro- and microdomains correspond to the electrical remodelling and contractile dysfunction of ventricular myocardium that could be used to identify pathological changes ranging from hypertrophy to failing heart. PMID- 22781818 TI - Age-dependent changes in ion channel mRNA expression in canine cardiac tissues. AB - The expression pattern of cardiac ion channels displays marked changes during ontogeny. This study was designed to follow the developmental changes in the expression of major ventricular and atrial ion channel proteins (including both pore forming and regulatory subunits) in canine cardiac tissues at the mRNA level using competitive reverse transcription polymerase chain reaction. Therefore, the corresponding mRNA levels were compared in myocardial tissues excised from embryonic (25-60 days of gestation) and adult (2-3 years old) canine hearts. Expression level of Kv4.3, Kv1.4, KChIP2, KvLQT1, and Cav3.2 mRNAs were higher in the adult than in the embryonic hearts, while expression of Nav1.5 and minK mRNAs were higher in the embryonic than in the adult myocardium. No change in Kir2.1, HERG, Kv1.5, and Cav1.2 mRNA was observed during ontogeny. Direction of the developmental change in the mRNA level, determined for any specific channel protein, was identical in the atrial and ventricular samples. The age-dependent increase observed in the expression of Kv4.3, Kv1.4, KChIP2, and KvLQT1 is congruent with the greater repolarization reserve of the adult myocardium, associated with higher densities of Ito and IKs. The results indicate that age dependent changes in the expression pattern of many ion channels are similar in canine and healthy human myocardium, therefore, canine cardiac muscle can be considered as a good model of studying developmental changes in the human heart. PMID- 22781820 TI - Impact of chronic ethanol intake of rat mothers on the seizure susceptibility of their immature male offspring. AB - The aim of present study was to examine the impact of prenatal ethanol exposure on seizure susceptibility of the offspring. Pregnant Wistar rats were compelled to drink either 10% or 20% ethanol solution, as the only drinking fluid since conception up to the weaning of their offspring at the age of 28 days. Pregnant and nursing rats of the control group drank water. Electrophysiological experiments (repeated electrical stimulation and analysis of cortical afterdischarges duration) were than performed on their immature offspring. Rat pups were tested on postnatal day 18, 25, and 35. Shortening of afterdischarges duration was observed in 18-day-old animals (mothers drank 20% ethanol) when compared with age matched controls and failure of post-ictal depression phenomenon was found in 25- and 35-day-old animals. Our findings signalize that ethanol exposure during pregnancy influences seizure susceptibility by acting on excitatory/inhibitory brain systems and this effect is dose- and age-dependent. PMID- 22781819 TI - Cortico-pontine theta carrier frequency phase shift across sleep/wake states following monoaminergic lesion in rat. AB - This study was aimed to explore the sleep/wake states related cortico-pontine theta carrier frequency phase shift following a systemically induced chemical axotomy of the monoaminergic afferents within a brain of the freely moving rats. Our experiments were performed in 14 adult, male Sprague Dawley rats, chronically implanted for sleep recording. We recorded sleep during baseline condition, following sham injection (saline i.p. 1 ml/kg), and every week for 5 weeks following injection of the systemic neurotoxins (DSP-4 or PCA; 1 ml/kg, i.p.) for chemical axotomy of the locus coeruleus (LC) and dorsal raphe (DR) axon terminals. After sleep/wake states identification, FFT analysis was performed on 5 s epochs. Theta carrier frequency phase shift (?Phi) was calculated for each epoch by averaging theta Fourier component phase shifts, and the ?Phi values were plotted for each rat in control condition and 28 days following the monoaminergic lesions, as a time for permanently established DR or LC chemical axotomy. Calculated group averages have shown that ?Phi increased between pons and cortex significantly in all sleep/wake states (Wake, NREM and REM) following the monoaminergic lesions, with respect to controls. Monoaminergic lesions established the pontine leading role in the brain theta oscillations during all sleep/wake states. PMID- 22781821 TI - Effect of normobaric oxygen treatment on oxidative stress and enzyme activities in guinea pig heart. AB - Normobaric oxygen (NBO) therapy is commonly applied for the treatment of various diseases, including myocardial infarctions, but its effectiveness is controversial. Potential adverse effects of hyperoxia are related to excessive formation of free radicals. In the present study we examined the effect of 60-h NBO treatment on lipid peroxidation (LPO), activity of manganese superoxide dismutase (Mn-SOD) and mitochondrial enzymes of energy metabolism in guinea pig heart. NBO treatment resulted in significant accumulation of thiobarbituric acid reactive substances and loss of Mn-SOD activity despite slight elevation of Mn SOD protein content. Activity of electron transport chain complex III decreased significantly, while activity of complex IV was slightly elevated and citrate synthase was unchanged. LPO, inhibition of Mn-SOD and complex III activities were more pronounced when inhaled oxygen was partially enriched with superoxide radical. In contrast, when O(2) was enriched with oxygen cation (O(2)?+), LPO and loss of Mn-SOD activity were prevented. Complex III activity in the O(2)?+ treated group remained depressed but activities of complex IV and citrate synthase were elevated. These data suggest that NBO treatment is associated with myocardial oxidative damage and attenuation of antioxidant defense, but these adverse effects can be partially attenuated by inhalation of O(2) enriched with oxygen cation. PMID- 22781822 TI - Influence of age on pain sensitivity in response to paw pressure and formalin injection in rats: a role of nitric oxide. AB - The effect of age on pain response to paw pressure and intraplantar formalin injection in rats is elucidated. Pain responses evoked by mechanical pressure on hind paw and intraplantar injection of formaldehyde (5%) into the hind paw were evaluated in groups of adult, young and aged male Sprague Dawley rats, after intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) injection of L arginine or NG-nitro-L-arginine methyl ester (L-NAME). Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining was done in the two groups. The results show that pain response was reduced in the aged rats and enhanced pain response to paw pressure in aged rats only. L-arginine (i.c.v.) had no effect on pain response to paw pressure in the two groups but enhanced biphasic pain response to formalin. L-NAME (i.p. and i.c.v.) suppressed pain response to paw pressure in the two groups. L-NAME (i.c.v.) suppressed pain response to formalin during the acute phase and enhanced it during the late phase. NADPH diaphorase activity was significantly greater in young rats. In conclusion, pain response is blunted in the aged rats. NO might be involved in mechanical nociception in aged rats and in formalin-induced nociception in both groups. NO blockade has an antinociceptive effect on pain response. Central NO has dual role in pain response evoked by formalin. PMID- 22781823 TI - Alteration of renal functional, oxidative stress and inflammatory indices following hepatic ischemia-reperfusion. AB - Liver ischemia/reperfusion (IR) injury is a complex phenomenon that may cause local as well as remote organ injuries. Reactive oxygen species (ROS) along with many pro- and anti- inflammatory cytokines are implicated in the development of organ injury. The renal functional, histological, oxidative stress and inflammatory indices were studied during a short and a longer period of liver IR. Rats were subjected to either sham operation or 90 min partial liver ischemia followed by 4 or 24 h of reperfusion. Serum ALT, AST, ALK and LDH levels, BUN and creatinine, renal MDA level, SOD and catalase activities were evaluated as well as serum IL-6 and IL-10 concentrations along with renal histological evaluation. Ninety minutes liver ischemia /4 h reperfusion caused an increase in BUN and renal MDA levels and a decrease in SOD and catalase activities. It also caused an increase in serum IL-6 and IL-10 levels. 24 h liver reperfusion resulted in a reduction in BUN levels and lower oxidative damages demonstrated by a decrease in renal MDA levels and an increase in renal SOD and catalase activities comparing to 4 h reperfusion group. Evaluations indicated improvement in histology such as less cytoplasmic vacuolation and lower tubular debris. Serum inflammatory indices (IL-6 and IL-10 levels) were also reduced. This study showed that liver IR damage causes renal injury including functional, inflammatory and oxidative status changes. The remote kidney damage was then improved by continuing reperfusion from 4 to 24 h. PMID- 22781824 TI - Histomorphometric features of ventral prostate in different aged rats after central ghrelin treatment. AB - Ghrelin, the endogenous ligand of growth hormone secretagogue receptor type 1a (GHS-R1a), has emerged as pleiotropic modulator of diverse biological functions, including energy homeostasis and recently, reproduction. The influence of intracerebroventricularly (ICV) administered ghrelin (1 MUg/day/rat for 5 days) to rats of different ages, i.e, peripubertal (38 days), adult (60 days) and middle-aged (180 days) on the ventral prostate size and morphology, serum testosterone levels and testis weight was examined. Ghrelin treatment significantly increased (p < 0.05) absolute ventral prostate weight in peripubertal and middle-aged rats, by 27% and 37% respectively, due to enhancement of epithelial and/or luminal compartment of the gland. In adult rats, both absolute and relative volumes of the acinar lumen were significantly decreased (p < 0.05), by 38% and 44% respectively, which was associated with significant increases (p < 0.05) in relative and absolute volumes of interacinar stroma, whereas ventral prostate weigh was unchanged. Irrespective of animal age, ghrelin did not affect serum testosterone levels. These are the first results of ghrelin treatment effects on healthy prostate appearance, which allow us to conclude that the rat ventral prostate response to ghrelin depends on the developmental stage of animals. Our results merit further investigations and may have clinical implications, especially in the light of data on possible role of ghrelin in prostate hypertrophy and adenomas. PMID- 22781826 TI - Scaling law: a global topological property of genetic sequences. AB - Here, we study the topological properties of genetic sequence by viewing the entire sequence as a whole. First, a systematic way of coding the gene combinations in a genetic sequence is developed. Next, we apply the coding method to real genetic sequences, and find a scale-free power-law distribution for some particular kinds of gene-combinations. Furthermore, we also present a model to reproduce the observed scale-free feature, which is based on three generic mechanisms: 1) Growth mechanism - genetic sequences expands continuously by the addition of new codon; 2) Preferential replication mechanism - the newly added codon at every time step is a replication of one of existed condons, and the probability that a codon is replicated is proportional to its emerging times in existed sequence; and 3) Mutation mechanism - following (2) the newly added codon has a small probability to mutate. To our knowledge, no report has been published to study the genetic sequences in such way. PMID- 22781825 TI - Comparison of blood pro/antioxidant levels before and after acute exercise in athletes and non-athletes. AB - The aims of our study were to assess the redox state of adolescent athletes and non-athletes both at rest and after acute exposure to physical load and to find relations between parameters of redox state and morphofunctional characteristics of subjects. 58 young handball players and 37 non-athletes were subjected to body composition analysis, measuring of maximal oxygen consumption and blood sampling immediately before and after a maximal progressive exercise test. At rest, athletes had significantly higher superoxide dismutase (SOD) and catalase (CAT) activity, higher levels of glutathione (GSH) and nitric oxide (NO) and lower levels of lipid peroxidation (TBARS) compared with non-athletes. A maximal exercise test induced statistically significant rise of superoxide anion radical (O2-), hydrogen peroxide (H2O2) and NO levels in non-athletes, while TBARS levels decreased. Athletes experienced the fall in NO levels and the fall in CAT activity. After exercise, athletes had significantly lower levels of O2- compared with non-athletes. Two way repeated measures ANOVA showed that the response of O2 , NO and TBARS to the exercise test was dependent on the sports engagement (training experience) of subjects. Significant correlations between morphofunctional and redox parameters were found. These results suggest that physical fitness affects redox homeostasis. PMID- 22781827 TI - Study of interaction of long-chain n-alcohols with fluid DOPC bilayers by a lateral pressure sensitive fluorescence probe. AB - The excimer 1,2-dipyrenedecanoyl-sn-glycero-3-phosphatidylcholine (dipy10PC) fluorescence probe was used to determine effects of aliphatic alcohols (CnH2n+1OH, n = 12-18 is the even number of carbons in alkyl chain) on fluid dioleoylphosphatidylcholine (DOPC) +dioleoylphosphatidylserine (DOPS) bilayers in multilamellar vesicles at molar ratio DOPC/DOPS = 24.7. The excimer to monomer fluorescence intensity ratio increases with the increase of CnH2n+1OH/DOPC molar ratio and decreases with the CnH2n+1OH alkyl chain length n at a constant CnH2n+1OH/DOPC = 0.4 molar ratio. These effects indicate changes in the bilayer lateral pressure on the level of pyrenyl moieties location. PMID- 22781828 TI - The role of quercetin in membrane stability. PMID- 22781830 TI - Shells of crystal field symmetries evidenced in oxide nano-crystals. AB - By the use of a point charge model based on the Judd-Ofelt transition theory, the luminescence from Eu(3+) ions embedded in Gd(2)O(3) clusters is calculated and compared to the experimental data. The main result of the numerical study is that without invoking any other mechanisms such as crystal disorder, the pure geometrical argument of the symmetry breaking induced by the particle surface has an influence on the energy level splitting. The modifications are also predicted to be observable in realistic conditions where unavoidable size dispersion has to be taken into account. The emission spectrum results from the contribution of three distinct regions; a cluster core, a cluster shell and the very surface, the latter being almost completely quenched in realistic conditions. Eventually, by detailing the spectra of the ions embedded at different positions in the cluster we get an estimate of about 0.5 nm for the extent of the crystal field induced Stark effect. Due to the similarity between Y (2)O(3) and Gd(2)O(3), these results also apply to Eu(3+) doped Y(2)O(3) nanoparticles. PMID- 22781832 TI - Precursor B-cell lymphoblastic leukemia of the arm mimicking neurogenic tumor: case report. AB - Precursor B-cell lymphoblastic lymphoma (PBLL) is an infrequent subtype of lymphoblastic lymphoma (LBL) that commonly affected site for the diagnosis is the skin, followed by the head and neck. In this report, we presented a special case of PBLL located at the left arm and detected with magnetic resonance imaging (MRI) and ultrasonography (US). This kind of PBLL is similar to a peripheral nerve tumor in clinical and radiographic manifestation. PMID- 22781833 TI - Spread of classic BSE prions from the gut via the peripheral nervous system to the brain. AB - An experimental oral bovine spongiform encephalopathy (BSE) challenge study was performed to elucidate the route of infectious prions from the gut to the central nervous system in preclinical and clinical infected animals. Tissue samples collected from the gut and the central and autonomic nervous system from animals sacrificed between 16 and 44 months post infection (mpi) were examined for the presence of the pathological prion protein (PrP(Sc)) by IHC. Moreover, parts of these samples were also bioassayed using bovine cellular prion protein (PrP(C)) overexpressing transgenic mice (Tgbov XV) that lack the species barrier for bovine prions. A distinct accumulation of PrP(Sc) was observed in the distal ileum, confined to follicles and/or the enteric nervous system, in almost all animals. BSE prions were found in the sympathetic nervous system starting at 16 mpi, and in the parasympathetic nervous system from 20 mpi. A clear dissociation between prion infectivity and detectable PrP(Sc) deposition became obvious. The earliest presence of infectivity in the brain stem was detected at 24 mpi, whereas PrP(Sc) accumulation was first detected after 28 mpi. In summary, our results decipher the centripetal spread of BSE prions along the autonomic nervous system to the central nervous system, starting already halfway in the incubation time. PMID- 22781834 TI - Adsorption of Reactive Blue 4 dye from water solutions by carbon nanotubes: experiment and theory. AB - Multi-walled and single-walled carbon nanotubes were used as nanoadsorbents for the successful removal of Reactive Blue 4 textile dye from aqueous solutions. The adsorbents were characterised by infrared and Raman spectroscopy, N(2) adsorption/desorption isotherms and scanning and transmission electron microscopy. The effects of pH, shaking time and temperature on adsorption capacity were studied. In the acidic pH region (pH 2.0), the adsorption of the dye was favourable using both adsorbents. The contact time to obtain equilibrium isotherms at 298-323 K was fixed at 4 hours for both adsorbents. The general order kinetic model provided the best fit to the experimental data compared with pseudo-first order and pseudo-second order kinetic adsorption models. For Reactive Blue 4 dye, the equilibrium data (298 to 323 K) were best fitted to the Liu isotherm model. The maximum sorption capacity for adsorption of the dye occurred at 323 K, attaining values of 502.5 and 567.7 mg g(-1) for MWCNT and SWCNT, respectively. Simulated dyehouse effluents were used to check the applicability of the proposed nanoadsorbents for effluent treatment (removal of 99.89% and 99.98%, for MWCNT and SWCNT, respectively). The interaction of Reactive Blue 4 textile dye with single-walled carbon nanotubes (SWCNTs) was investigated using first principles calculations based on density functional theory. Results from ab initio calculations indicated that Reactive Blue 4 textile dye could be adsorbed on SWCNT through an electrostatic interaction; these results are in agreement with the experimental predictions. PMID- 22781835 TI - Prolonged hyperoxia preconditioning attenuates behavioral symptoms of 6 hydroxydopamine-induced Parkinsonism. AB - OBJECTIVES: Several lines of evidences show that hyperoxia preconditioning provides neuronal protection against central nervous system ischemic damages. Common pathways including mitochondrial dysfunction, apoptosis, and caspase activation are involved in acute neurodegeneration (e.g. after cerebral ischemia) and chronic neurodegeneration (e.g. neuronal death in Parkinson's disease). The aim of the present research was to study the effect of hyperoxia preconditioning on 6-hydroxydopamine (6-OHDA)-induced Parkinsonism. METHODS: Male Wistar rats were first subjected to either air with high oxygen concentration (>90%) or atmospheric air for prolonged (24 hours) or intermittent (six consecutive days, 4 hours each day) periods and then 6-OHDA was injected into their left striatums by stereotaxic surgery. Development and severity of the 6-OHDA-induced Parkinsonism was assessed using apomorphine-induced rotational test, elevated body swing test, and rotarod test within 2-5 weeks after the surgery. RESULTS: Significant data obtained in rats treated with prolonged hyperoxia, but not the intermittent hyperoxia. In these rats, the number of apomorphine-induced rotations was ~60% lower than that in control and sham groups. Rats belonging to the prolonged hyperoxia group also showed considerably better motor performance and learning pattern in rotarod test. These results were confirmed by the data obtained in the elevated body swing test. DISCUSSION: Our findings show that the prolonged hyperoxia preconditioning attenuates the behavioral symptoms of 6-OHDA-induced Parkinsonism. Considering the well-known correlation between dopaminergic neuronal death in the substantia nigra and the behavioral symptoms of 6-OHDA induced Parkinsonism, it could be speculated that the prolonged hyperoxia preconditioning induces the mechanisms that provide dopaminergic neuroprotection against Parkinsonism-induced toxins. PMID- 22781836 TI - Control of stem cell homeostasis via interlocking microRNA and microProtein feedback loops. AB - Stem cells in the shoot apex of plants produce cells required for the formation of new leaves. Adult leaves are composed of multiple tissue layers arranged along the dorso-ventral (adaxial/abaxial) axis. Class III homeodomain leucine zipper (HD-ZIPIII) transcription factors play an important role in the set-up of leaf polarity in plants. Loss of HD-ZIPIII function results in strongly misshapen leaves and in severe cases fosters the consumption of the apical stem cells, thus causing a growth arrest in mutant plants. HD-ZIPIII mRNA is under tight control by microRNAs 165/166. In addition to the microRNA-action a second layer of regulation is established by LITTLE ZIPPER (ZPR)-type microProteins, which can interact with HD-ZIPIII proteins, forming attenuated protein complexes. Here we show that REVOLUTA (REV, a member of the HD-ZIPIII family) directly regulates the expression of ARGONAUTE10 (AGO10), ZPR1 and ZPR3. Because AGO10 was shown to dampen microRNA165/6 function, REV establishes a positive feedback loop on its own activity. Since ZPR-type microProteins are known to reduce HD-ZIPIII protein activity, REV concomitantly establishes a negative feedback loop. We propose that the interconnection of these microRNA/microProtein feedback loops regulates polarity set-up and stem cell activity in plants. PMID- 22781837 TI - Fast capture and separation of, and luminescent probe for, pollutant chromate using a multi-functional cationic heterometal-organic framework. AB - We present one 3D cationic MOF (1-ClO(4)), which exhibits high thermal stability and strong alkali resistance. More importantly, it displays fast, selective capture of, and acts as a luminescent probe for, pollutant CrO(4)(2-) by anion exchange. Additionally, 1-ClO(4) exhibits interesting slow magnetic relaxation behavior at low temperature. PMID- 22781838 TI - Cortico-subcortical neuromodulation involved in the amelioration of prepulse inhibition deficits in dopamine transporter knockout mice. AB - Prepulse inhibition (PPI) deficits are among the most reproducible phenotypic markers found in schizophrenic patients. We recently reported that nisoxetine, a selective norepinephrine transporter (NET) inhibitor, reversed the PPI deficits that have been identified in dopamine transporter (DAT) knockout (KO) mice. However, the mechanisms underlying nisoxetine-induced PPI recovery in DAT KO mice were unclear in previous experiments. To clarify these mechanisms, PPI was tested after microinjections of nisoxetine into the medial prefrontal cortex (mPFc) or nucleus accumbens (NAc) in wildtype (WT) and DAT KO mice. c-Fos immunohistochemistry provided an indicator of neural activation. Multiple fluorescent-labeling procedures and the retrograde tracer fluorogold were employed to identify nisoxetine-activated neurons and circuits. Systemic nisoxetine activated the mPFc, the NAc shell, the basolateral amygdala, and the subiculum. Infusions of nisoxetine into the mPFc reversed PPI deficits in DAT KO mice, but produced no changes in WT mice, while infusion of nisoxetine into the NAc had no effect on PPI in both WT and DAT KO mice. Experiments using multiple fluorescent labeling/fluorogold revealed that nisoxetine activates presumed glutamatergic pyramidal cells that project from the mPFc to the NAc. Activated glutamatergic projections from the mPFc to the NAc appear to have substantial roles in the ability of a NET inhibitor to normalize PPI deficits in DAT KO. Thus, this data suggest that selective NET inhibitors such as nisoxetine might improve information processing deficits in schizophrenia via regulation of cortico-subcortical neuromodulation. PMID- 22781839 TI - Viral-mediated knockdown of mGluR7 in the nucleus accumbens mediates excessive alcohol drinking and increased ethanol-elicited conditioned place preference in rats. AB - Whether metabotropic glutamate 7 (mGluR7) -activation enhances or diminishes the reinforcing properties of psychostimulants remains unclear. We have previously shown that systemic mGluR7 activation reduced alcohol consumption and preference as well as locomotor-stimulating and rewarding properties of ethanol. In this study, we further examined the contribution of mGluR7 on the effect of ethanol within the nucleus accumbens (NAcc), a neural target for many drugs of abuse. Using short hairpin RNA (shRNA)-expressing lentiviral vectors (LV) to alter locally the activity of mGluR7 in male rats, we have shown that blocking mGluR7 expression increased ethanol consumption and preference in a two-bottle choice drinking paradigm with no effect either on saccharin or on quinine used for taste discrimination. In addition, mGluR7 knockdown increases preference for environments previously paired with low doses of ethanol in the conditioned place preference (CPP) test, as it shifted the dose-response curve for ethanol CPP to the left, indicating alterations in the rewarding effects of alcohol. More importantly, mGluR7 blockade in the dorsal striatum (DS) neither affected ethanol consumption nor ethanol-elicited CPP. These results show that levels of mGluR7 in the NAcc regulate responsiveness to alcohol. Taken together, these findings clearly demonstrate that mGluR7 signaling within the NAcc is a key modulator of functional responses to ethanol and offer an important target for regulating the addictive effects of alcohol. PMID- 22781840 TI - The impact of MeCP2 loss- or gain-of-function on synaptic plasticity. AB - Methyl-CpG-binding protein 2 (MeCP2) is a transcriptional regulator of gene expression that is an important epigenetic factor in the maintenance and development of the central nervous system. The neurodevelopmental disorders Rett syndrome and MECP2 duplication syndrome arise from loss-of-function and gain-of function alterations in MeCP2 expression, respectively. Several animal models have been developed to recapitulate the symptoms of Rett syndrome and MECP2 duplication syndrome. Cell morphology, neurotransmission, and cellular processes that support learning and memory are compromised as a result of MeCP2 loss- or gain-of-function. Interestingly, loss-of-MeCP2 function and MeCP2 overexpression trigger diametrically opposite changes in synaptic transmission. These findings indicate that the precise regulation of MeCP2 expression is a key requirement for the maintenance of synaptic and neuronal homeostasis and underscore its importance in central nervous system function. This review highlights the functional role of MeCP2 in the brain as a regulator of synaptic and neuronal plasticity as well as its etiological role in the development of Rett syndrome and MECP2 duplication syndrome. PMID- 22781842 TI - Variation in the glucocorticoid receptor gene at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child cortisol reactivity and behavior. AB - Prenatal maternal psychopathology affects child development, but some children seem more vulnerable than others. Genetic variance in hypothalamic-pituitary adrenal axis genes may influence the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems. This hypothesis was tested in the Generation R Study, a population-based cohort from fetal life onward. In total, 1727 children of Northern European descent and their mothers participated in this study and were genotyped for variants in the glucocorticoid receptor (GR) gene (rs6189/rs6190, rs10052957, rs41423247, rs6195, and rs6198) and the FK506 binding protein 5 (FKBP5) gene (rs1360780). Prenatal maternal psychological symptoms were assessed at 20 weeks pregnancy and child behavior was assessed by both parents at 3 years. In a subsample of 331 children, data about cortisol reactivity were available. Based on power calculations, only those genetic variants with sufficient minor allele frequencies (rs41423247, rs10052957, and rs1360780) were included in the interaction analyses. We found that variation in GR at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems (beta 0.41, SE 0.16, p=0.009). This prenatal interaction effect was independent of mother's genotype and maternal postnatal psychopathology, and not found for prenatal psychological symptoms of the father. Moreover, the interaction between rs41423247 and prenatal psychological symptoms was also associated with decreased child cortisol reactivity (beta -2.30, p-value 0.05). These findings emphasize the potential effect of prenatal gene-environment interaction, and give insight in possible mechanisms accounting for children's individual vulnerability to develop emotional and behavioral problems. PMID- 22781841 TI - DNA methylation and its basic function. AB - In the mammalian genome, DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5 methylcytosine. DNA methylation regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factor(s) to DNA. During development, the pattern of DNA methylation in the genome changes as a result of a dynamic process involving both de novo DNA methylation and demethylation. As a consequence, differentiated cells develop a stable and unique DNA methylation pattern that regulates tissue-specific gene transcription. In this chapter, we will review the process of DNA methylation and demethylation in the nervous system. We will describe the DNA (de)methylation machinery and its association with other epigenetic mechanisms such as histone modifications and noncoding RNAs. Intriguingly, postmitotic neurons still express DNA methyltransferases and components involved in DNA demethylation. Moreover, neuronal activity can modulate their pattern of DNA methylation in response to physiological and environmental stimuli. The precise regulation of DNA methylation is essential for normal cognitive function. Indeed, when DNA methylation is altered as a result of developmental mutations or environmental risk factors, such as drug exposure and neural injury, mental impairment is a common side effect. The investigation into DNA methylation continues to show a rich and complex picture about epigenetic gene regulation in the central nervous system and provides possible therapeutic targets for the treatment of neuropsychiatric disorders. PMID- 22781843 TI - Epigenetic inheritance of disease and disease risk. AB - Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations. This review examines the challenging possibility that epigenetic changes induced by environmental factors can contribute to some of the inheritance of disease and disease risk. This concept has immense implications for the understanding of biological functions and disease etiology, and provides potential novel strategies for diagnosis and treatment. Examples of epigenetic inheritance relevant to human disease, such as the detrimental effects of traumatic stress or drug/toxic exposure on brain functions, are reviewed. Different possible routes of transmission of epigenetic information involving the germline or germline independent transfer are discussed, and different mechanisms for the maintenance and transmission of epigenetic information like chromatin remodeling and small noncoding RNAs are considered. Future research directions and remaining major challenges in this field are also outlined. Finally, the adaptive value of epigenetic inheritance, and the cost and benefit of allowing acquired epigenetic marks to persist across generations is critically evaluated. PMID- 22781844 TI - Transient inactivation of the neonatal ventral hippocampus impairs attentional set-shifting behavior: reversal with an alpha7 nicotinic agonist. AB - Cognitive deficits represent a core symptom cluster in schizophrenia that are thought to reflect developmental dysregulations within a neural system involving the ventral hippocampus (VH), nucleus accumbens (NAC), and prefrontal cortex (PFC). The present experiments determined the cognitive effects of transiently inactivating VH in rats during a sensitive period of development. Neonatal (postnatal day 7, PD7) and adolescent (PD32) male rats received a single bilateral infusion of saline or tetrodotoxin (TTX) within the VH to transiently inactivate local circuitry and efferent outflow. Rats were tested as adults on an attentional set-shifting task. Performance in this task depends upon the integrity of the PFC and NAC. TTX infusions did not affect the initial acquisition or ability to learn an intra-dimensional shift. However, TTX rats required a greater number of trials than did controls to acquire the first reversal and extra-dimensional shift (ED) stages. These impairments were age and region-specific as rats infused with TTX into the VH at PD32, or into the dorsal hippocampus at PD7, exhibited performance in the task similar to that of controls. Finally, acute systemic administration of the partial alpha7 nicotinic acetylcholine receptor (nAChR) agonist SSR 180711 (3.0 mg/kg) eliminated the TTX induced performance deficits. Given that patients with schizophrenia exhibit hippocampal pathophysiology and deficits in the ED stages of set-shifting tasks, our results support the significance of transient hippocampal inactivation as an animal model for studying the cognitive impairments in schizophrenia as well as the pro-cognitive therapeutic potential of alpha7 nAChR agonists. PMID- 22781846 TI - Catheter-assisted 18F-FDG-PET/CT imaging of primary bladder cancer: a prospective study. AB - OBJECTIVE: The purpose of this study was to prospectively investigate the value of a standardized 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT) protocol for imaging of primary bladder cancer, using standardized bladder flushing and filling. METHODS: We included 19 patients with cT1-4 bladder cancer. A Foley catheter was inserted before 18F-FDG injection. PET/CT imaging was performed according to four bladder protocols: (1) bladder empty; (2) bladder empty after flushing; (3) bladder filled with 50 ml saline; and (4) bladder filled with 100 ml saline. Tumour visibility was assessed and compared with histopathology or CT and cystoscopy. RESULTS: The procedure was successfully completed in 16 out of 19 patients. The reference standard revealed a bladder tumour in 16 out of 19 patients. Sensitivity of protocols 1 and 2 was 0.38 [95% confidence interval (CI), 0.16-0.64] compared with 0.63 (95% CI, 0.36-0.84) for protocols 3 and 4. CONCLUSION: Flushing and subsequent retrograde filling of the bladder results in the highest rate of tumour visualization and quantification. Flushing alone is inferior. PMID- 22781845 TI - Effects of inhibitor of kappaB kinase activity in the nucleus accumbens on emotional behavior. AB - Inhibitor of kappaB kinase (IkappaK) has historically been studied in the context of immune response and inflammation, but recent evidence demonstrates that IkappaK activity is necessary and sufficient for regulation of neuronal function. Chronic social defeat stress of mice increases IkappaK activity in the nucleus accumbens (NAc) and this increase is strongly correlated to depression-like behaviors. Inhibition of IkappaK signaling results in a reversal of chronic social defeat stress-induced social avoidance behavior. Here, we more completely define the role of IkappaK in anxiety and depressive-like behaviors. Mice underwent stereotaxic microinjection of a herpes simplex virus expressing either green fluorescent protein, a constitutively active form of IkappaK (IkappaKca), or a dominant negative form of IkappaK into the NAc. Of all three experimental groups, only mice expressing IkappaKca show a behavioral phenotype. Expression of IkappaKca results in a decrease in the time spent in the non-periphery zones of an open field arena and increased time spent immobile during a forced swim test. No baseline differences in sucrose preference were observed, but following the acute swim stress we noted a marked reduction in sucrose preference. To determine whether IkappaK activity alters responses to other acute stressors, we examined behavior and spine morphology in mice undergoing an acute social defeat stress. We found that IkappaKca enhanced social avoidance behavior and promoted thin spine formation. These data show that IkappaK in NAc is a critical regulator of both depressive- and anxiety-like states and may do so by promoting the formation of immature excitatory synapses. PMID- 22781847 TI - Skin contamination of nuclear medicine technologists: incidence, routes, dosimetry and decontamination. AB - OBJECTIVE: Nuclear medicine technologists are exposed daily to the risk of skin contamination with radiopharmaceuticals. This study deal with the different elements associated with skin contaminations. METHODS: To assess the incidence, routes and contamination activities, a long-term on-site survey was organized using a measurement system built in-house, together with a protocol based on fast detection, localization and quantification. Dosimetry calculations were carried out using Monte Carlo simulations and combined with the efficacy of skin decontamination, which was studied both in the context of daily practice of nuclear medicine and in vitro using pig skin samples. RESULTS: In 10 months 560 inspections were carried out. Local contamination was found on the fingers of nuclear medicine technologists in 40 cases, but the increasing awareness caused a significant reduction over time. The measured activities ranged from 211 Bq/cm2 to 460 kBq/cm2, resulting in cumulated skin doses between 0.02 and 809 mSv. The poor efficacy of the decontamination during daily practice is supported by the in vitro results. The course of a contamination is characterized by an effective first decontamination, followed by relatively ineffective steps. The efficacy of dedicated decontamination agents is indicated in only a few cases. CONCLUSION: Skin contamination can be found in large doses on the skin among nuclear medicine technologists. Single contaminations can result in local skin doses exceeding the yearly dose limit because of the contribution of electrons at shallow depths and should therefore be prevented at any time. The use of a neutral hand soap should generally be preferred during decontamination. A general simplified method is proposed to assess the skin dose after a contamination with 99mTc-labelled radiopharmaceuticals or 18F-fluorodeoxyglucose. PMID- 22781848 TI - Preparation of an awake mouse for recording neural responses and injecting tracers. AB - It is well known that anesthesia alters neural response properties in various regions of the brain. In the auditory system, fundamental response properties of brainstem neurons including threshold, frequency specificity, and inhibitory sidebands are altered in significant ways under anesthesia. These observations prompted physiologists to seek ways to record from single neurons without the contaminating effects of anesthesia. One result was a decerebrate preparation, where the brainstem was completely transected at the level of the midbrain. The drawbacks of this preparation are a formidable surgery, the elimination of descending projections from the forebrain, and an inability to use sensory stimulation to examine structures above the midbrain. A different strategy has been to implant electrode arrays chronically to record from single neurons and multiunit clusters while the animal is awake and/or behaving. These techniques however are not compatible with injecting tracer dyes after first electrophysiologically characterizing a brain structure. To avoid altering neural response properties with anesthetics while recording electrophysiological response properties from single neurons, we have adapted a head restraint technique long used in bats to mouse. Using this method, we are able to conduct electrophysiological recordings over several days in the unanesthetized mouse. At the end of the recording sessions, we can then inject a dye to reconstruct electrode positions and recording sites or inject a tracer so that pathways to and from the recording loci can be determined. This method allows for well isolated single neuron recordings over multiple days without the use anesthetics. PMID- 22781849 TI - Multilevel approaches toward understanding antisocial behavior: current research and future directions. PMID- 22781851 TI - Childhood maltreatment and illicit drug use in middle adulthood: the role of neighborhood characteristics. AB - This paper examined whether childhood maltreatment increases the risk of living in neighborhoods with less desirable characteristics (i.e., more disorder and disadvantage, less social cohesion, social control and advantage, and fewer resources) in middle adulthood and whether these neighborhood characteristics influence subsequent illicit drug use. Using a prospective cohort design study, court documented cases of childhood abuse and neglect and matched controls (n = 833) were first interviewed as young adults (mean age = 29 years) from 1989 to 1995 and again in middle adulthood from 2000 to 2002 (mean age = 40 years) and 2003 to 2005 (mean age = 41 years). In middle adulthood, individuals with histories of childhood abuse and neglect were more likely to live in neighborhoods with more disorder and disadvantage and less social cohesion and advantage compared to controls and to engage in illicit drug use during the past year. Path analyses showed an indirect effect on illicit drug use via neighborhood disorder among maltreated children, even after accounting for drug abuse symptoms in young adulthood, although this was sex specific and race specific, affecting women and Whites. Overall, child abuse and neglect places children on a negative trajectory that dynamically influences negative outcomes at multiple levels into middle adulthood. PMID- 22781850 TI - Supportive parenting mediates neighborhood socioeconomic disparities in children's antisocial behavior from ages 5 to 12. AB - We report a graded relationship between neighborhood socioeconomic status (SES) and children's antisocial behavior that (a) can be observed at school entry, (b) widens across childhood, (c) remains after controlling for family-level SES and risk, and (d) is completely mediated by maternal warmth and parental monitoring (defined throughout as supportive parenting). The children were participants in the Environmental Risk Longitudinal Twin Study (N = 2,232), which prospectively tracked the development of children and their neighborhoods across childhood. Direct and independent effects of neighborhood-level SES on children's antisocial behavior were observed as early as age 5, and the gap between children living in deprived versus more affluent neighborhoods widened as children approached adolescence. By age 12, the effect of neighborhood SES on children's antisocial behavior was as large as the effect observed for our most robust predictor of antisocial behavior: sex (Cohen d = 0.51 when comparing children growing up in deprived vs. more affluent neighborhoods in comparison to Cohen d = 0.53 when comparing antisocial behavior among boys vs. girls). However, these relatively large differences in children's levels and rate of change in antisocial behavior across deprived versus more affluent neighborhoods were completely mediated by supportive parenting practices. The implications of our findings for studying and reducing socioeconomic disparities in antisocial behavior among children are discussed. PMID- 22781852 TI - Advancing paternal age and offspring violent offending: a sibling-comparison study. AB - Children born to older fathers are at higher risk to develop severe psychopathology (e.g., schizophrenia and bipolar disorder), possibly because of increased de novo mutations during spermatogenesis with older paternal age. Because severe psychopathology is correlated with antisocial behavior, we examined possible associations between advancing paternal age and offspring violent offending. Interlinked Swedish national registers provided information on fathers' age at childbirth and violent criminal convictions in all offspring born from 1958 to 1979 (N = 2,359,921). We used ever committing a violent crime and number of violent crimes as indices of violent offending. The data included information on multiple levels; we compared differentially exposed siblings in within-family analyses to rigorously test causal influences. In the entire population, advancing paternal age predicted offspring violent crime according to both indices. Congruent with a causal effect, this association remained for rates of violent crime in within-family analyses. However, in within-family analyses, we found no association with ever committing a violent crime, suggesting that factors shared by siblings (genes and environment) confounded this association. Life-course persistent criminality has been proposed to have a partly biological etiology; our results agree with a stronger biological effect (i.e., de novo mutations) on persistent violent offending. PMID- 22781853 TI - Externalizing problems, attention regulation, and household chaos: a longitudinal behavioral genetic study. AB - Previous research documented a robust link between difficulties in self regulation and development of externalizing problems (i.e., aggression and delinquency). In this study, we examined the longitudinal additive and interactive genetic and environmental covariation underlying this well established link using a twin design. The sample included 131 pairs of monozygotic twins and 173 pairs of same-sex dizygotic twins who participated in three waves of annual assessment. Mothers and fathers provided reports of externalizing problems. Teacher report and observer rating were used to assess twin's attention regulation. The etiology underlying the link between externalizing problems and attention regulation shifted from a common genetic mechanism to a common environmental mechanism in the transition across middle childhood. Household chaos moderated the genetic variance of and covariance between externalizing problems and attention regulation. The genetic influence on individual differences in both externalizing problems and attention regulation was stronger in more chaotic households. However, higher levels of household chaos attenuated the genetic link between externalizing problems and attention regulation. PMID- 22781854 TI - Association between a marker for prenatal testosterone exposure and externalizing behavior problems in children. AB - Prenatal androgen exposure has been associated with aggressive behavior in adults. It is less clear whether this association holds for childhood externalizing behavior. This study tests the hypothesis that increased prenatal androgen exposure is associated with aggressive behavior and attention problems in childhood. The ratio of the length of the second finger digit relative to the fourth digit, which is a marker for prenatal testosterone exposure, was assessed in 239 male and female fifth grade schoolchildren from Jintan, China, together with parent and teacher ratings of aggression and attention problems. Increased aggression and attention problems were both significantly associated with a lower ratio of the length of the second finger digit relative to the fourth digit ratios in boys but not girls. The effects remained significant after controlling for early adversity. These findings are the first to establish a relationship between an indirect indicator of fetal androgen exposure and any child psychopathology in Chinese children, and the observed effect size in boys was stronger than in male adults in Western studies. The results provide limited cross-cultural support for the importance of prenatal androgen exposure in contributing to the development of externalizing behavior problems in children, and they suggest that such effects may be specific to boys who may be relatively more vulnerable to early prenatal influences. PMID- 22781855 TI - Toward a new understanding of legacy of early attachments for future antisocial trajectories: evidence from two longitudinal studies. AB - Early parent-child attachment has been extensively explored as a contributor to children's future adaptive or antisocial outcomes, but the specific developmental mechanisms remain to be fully understood. We examined long-term indirect developmental sequelae of early security in two longitudinal community samples followed from infancy to early school age: the Family Study (102 mothers, fathers, and infants) and the Parent-Child Study (112 mothers and infants). Constructs at multiple levels (child characteristics, parent-child security, parental discipline, and child antisocial outcomes) were assessed using a range of methods (extensive behavioral observations in a variety of settings, informants' ratings). Both studies supported the proposed model of infant attachment as a potent catalyst that moderates future developmental socialization trajectories, despite having few long-term main effects. In insecure dyads, a pattern of coercion emerged between children who were anger prone as toddlers and their parents, resulting in parents' increased power-assertive discipline. Power assertion in turn predicted children's rule-breaking conduct and a compromised capacity to delay in laboratory paradigms, as well as oppositional, disruptive, callous, and aggressive behavior rated by parents and teachers at early school age. This causal chain was absent in secure dyads, where child anger proneness was unrelated to power assertion, and power assertion was unrelated to antisocial outcomes. Early insecurity appeared to act as a catalyst for the parent-child dyad embarking on a mutually adversarial path toward antisocial outcomes, whereas security defused such a maladaptive dynamic. The possible mechanisms of those effects were proposed. PMID- 22781856 TI - Pathways and processes of risk in associations among maternal antisocial personality symptoms, interparental aggression, and preschooler's psychopathology. AB - Two studies examined the nature and processes underlying the joint role of interparental aggression and maternal antisocial personality as predictors of children's disruptive behavior problems. Participants for both studies included a high-risk sample of 201 mothers and their 2-year-old children in a longitudinal, multimethod design. Addressing the form of the interplay between interparental aggression and maternal antisocial personality as risk factors for concurrent and prospective levels of child disruptive problems, the Study 1 findings indicated that maternal antisocial personality was a predictor of the initial levels of preschooler's disruptive problems independent of the effects of interparental violence, comorbid forms of maternal psychopathology, and socioeconomic factors. In attesting to the salience of interparental aggression in the lives of young children, latent difference score analyses further revealed that interparental aggression mediated the link between maternal antisocial personality and subsequent changes in child disruptive problems over a 1-year period. To identify the family mechanisms that account for the two forms of intergenerational transmission of disruptive problems identified in Study 1, Study 2 explored the role of children's difficult temperament, emotional reactivity to interparental conflict, adrenocortical reactivity in a challenging parent-child task, and experiences with maternal parenting as mediating processes. Analyses identified child emotional reactivity to conflict and maternal unresponsiveness as mediators in pathways between interparental aggression and preschooler's disruptive problems. The findings further supported the role of blunted adrenocortical reactivity as an allostatic mediator of the associations between parental unresponsiveness and child disruptive problems. PMID- 22781857 TI - Development of fear and guilt in young children: stability over time and relations with psychopathology. AB - Extremes in fearful temperament have long been associated with later psychopathology and risk pathways. Whereas fearful children are inhibited and anxious and avoid novel events, fearless individuals are disinhibited and more likely to engage in aggressive behavior. However, very few studies have examined fear in infants from a multimethod and prospective longitudinal perspective. This study had the following objectives: to examine behavioral, maternal reported, and physiological indices of fearful temperament in infancy, together with their relations and stability over time; and to establish whether early indices of fear predict fear later in toddlerhood. We also examined the association between behavioral and physiological measures of fear and guilt and whether fear in infancy predicts guilt in toddlers. Finally, we investigated infant risk factors for later psychopathology. We recorded skin conductance level (SCL) and heart rate (HR) and observed children's responses during a Laboratory Temperament Assessment Battery fear paradigm across the first 3 years of life and during a guilt induction procedure at age 3 (N = 70). The results indicate that different measures of infant fear were associated across time. Observed fearlessness in infancy predicted observed fearlessness and low levels of SCL arousal to fear and guilt in toddlers. Low levels of HR and SCL to fear in infancy predicted low levels of physiological arousal to the same situation and to guilt 2 years later. Fear and guilt were significantly associated across measures. Finally, toddlers with clinically significant internalizing problems at age 3 were already notably more fearful in Year 1 as reflected by their significantly higher HR levels. The results indicated that assessments of children in infancy are predictive of how these children react 2 years later and therefore lend support to the idea that the emotional thermostat is set in the first 3 years of life. They also showed, for the first time, that infant fear is a predictor of guilt, which is an emotion that develops later. The implications of these findings for our understanding of developmental psychopathology are discussed. PMID- 22781859 TI - Pathways from harsh parenting to adolescent antisocial behavior: a multidomain test of gender moderation. AB - We tested for gender moderation within a multidomain model of antisocial behavior (ASB) among community youth, drawn from the Project on Human Development in Chicago Neighborhoods study. Youths (N = 1,639) were 9 to 12 years old at baseline and were followed for two additional waves, spaced approximately 2.5 years apart. We hypothesized that harsh and physically coercive parenting, a familial level risk factor, would impact individual level risk factors for ASB, such as childhood temperament ratings of emotionality and inhibitory control, and preadolescent externalizing and internalizing symptoms, as well as involvement with antisocial peers. We further hypothesized that this process and its impact on ASB would be moderated by gender. We used both multiple indicator multiple causes and multiple group analyses to test for gender moderation and a structural equation modeling multiple mediation framework to evaluate the strength of indirect effects. We tested the role of family, individual, and peer level influences on ASB, after accounting for the role of known contextual factors, including poverty, race, and neighborhood. Our overall model fit the data well for males and females, indicating harsh parenting, disinhibition, emotionality, and peers exert a strong influence on risk for ASB. Gender moderated the pathway from harsh parenting to externalizing behavior, such that this was a significant pathway for girls, but not boys. We discussed the importance of these findings with regard to intervention planning for youth at risk for ASB and future gender informed models of ASB. PMID- 22781858 TI - Temperamental exuberance and executive function predict propensity for risk taking in childhood. AB - The present study utilized a multilevel approach to examine developmental trajectories in risk-taking propensity. We examined the moderating role of specific executive function components, attention shifting and inhibitory control, on the link between exuberant temperament in infancy and propensity for risk taking in childhood. Risk taking was assessed using a task previously associated with sensation seeking and antisocial behaviors. Two hundred ninety one infants were brought into the lab and behaviors reflecting exuberance were observed at 4, 9, 24, and 36 months of age. Executive function was assessed at 48 months of age. Risk-taking propensity was measured when children were 60 months of age. The results indicated that exuberance and attention shifting, but not inhibitory control, significantly interacted to predict propensity for risk taking. Exuberance was positively associated with risk-taking propensity among children who were relatively low in attention shifting but unrelated for children high in attention shifting. These findings illustrated the multifinality of developmental outcomes for temperamentally exuberant young children and pointed to the distinct regulatory influences of different executive functions for children of differing temperaments. Attention shifting likely affords a child the ability to consider both positive and negative consequences and moderates the relation between early exuberance and risk-taking propensity. PMID- 22781860 TI - Early predictors of boys' antisocial trajectories. AB - Despite the large number of studies tracing patterns of youth antisocial behavior (AB) during adolescence, few have prospective data on the developmental precursors of AB beginning during infancy. Using a cohort of 268 low-income boys first assessed at 18 months, the current study examined predictors of early- and late-starting trajectories of AB assessed during early childhood and early adolescence. Four trajectory groups were identified, including early- and late starting groups, a low stable group, and a high decreasing group, characterized by multiple risk factors during early childhood and early adolescence. During early childhood, parenting and maternal depression discriminated two AB trajectory groups, an early-starting and a high decreasing group, who would go on to demonstrate a high preponderance of juvenile court involvement (60% to 79%) and elevated rates of clinical depression 13 to 15 years later. The results were discussed in reference to targeting malleable family risk factors during early childhood associated with patterns of AB and mental health disorders during adolescence. PMID- 22781861 TI - Intergenerational influences on early alcohol use: independence from the problem behavior pathway. AB - Conduct problems are a general risk factor for adolescent alcohol use. However, their role in relation to alcohol-specific risk pathways of intergenerational transmission of alcohol use is not well understood. Further, the roles of alcohol specific contextual influences on children's early alcohol use have been little examined. In a 20-year prospective, multimethod study of 83 fathers and their 125 children, we considered the predictors of child alcohol use by age 13 years. The predictors included fathers' adolescent antisocial behavior and alcohol use, both parents' adult alcohol use, norms about and encouragement of child use, parental monitoring, child-reported exposure to intoxicated adults, and parent-reported child externalizing behaviors. Path models supported an association between fathers' adolescent alcohol use and children's use (beta = 0.17) that was not better explained by concurrent indicators of fathers' and children's general problem behavior. Fathers' and mothers' adult alcohol use uniquely predicted child use, and exposure to intoxicated adults partially mediated the latter path. Other family risk mechanisms were not supported. However, parental alcohol use and child alcohol use were linked in expected ways with family contextual conditions known to set the stage for alcohol use problems later in adolescence. PMID- 22781862 TI - The effects of child maltreatment on early signs of antisocial behavior: genetic moderation by tryptophan hydroxylase, serotonin transporter, and monoamine oxidase A genes. AB - Gene-environment interaction effects in predicting antisocial behavior in late childhood were investigated among maltreated and nonmaltreated low-income children (N = 627, M age = 11.27). Variants in three genes were examined: tryptophan hydroxylase 1 (TPH1), serotonin transporter linked polymorphic region (5-HTTLPR), and monoamine oxidase A (MAOA) upstream variable number tandem repeat. In addition to child maltreatment status, we considered the impact of maltreatment subtypes, developmental timing of maltreatment, and chronicity. Indicators of antisocial behavior were obtained from self-, peer, and adult counselor reports. In a series of analyses of covariance, child maltreatment and its parameters demonstrated strong main effects on early antisocial behavior as assessed by all report forms. Genetic effects operated primarily in the context of gene-environment interactions, moderating the impact of child maltreatment on outcomes. Across the three genes, among nonmaltreated children no differences in antisocial behavior were found based on genetic variation. In contrast, among maltreated children specific polymorphisms of TPH1, 5-HTTLPR, and MAOA were each related to heightened self-report of antisocial behavior; the interaction of 5 HTTLPR and developmental timing of maltreatment also indicated more severe antisocial outcomes for children with early onset and recurrent maltreatment based on genotype. TPH1 and 5-HTTLPR interacted with maltreatment subtype to predict peer reports of antisocial behavior; genetic variation contributed to larger differences in antisocial behavior among abused children. The TPH1 and 5 HTTLPR polymorphisms also moderated the effects of maltreatment subtype on adult reports of antisocial behavior; again, the genetic effects were strongest for children who were abused. In addition, TPH1 moderated the effect of developmental timing of maltreatment and chronicity on adult reports of antisocial behavior. The findings elucidate how genetic variation contributes to identifying which maltreated children are most vulnerable to antisocial development. PMID- 22781863 TI - Effects of divorce on Dutch boys' and girls' externalizing behavior in Gene * Environment perspective: diathesis stress or differential susceptibility in the Dutch Tracking Adolescents' Individual Lives Survey study? AB - The effects of divorce on children's behavioral development have proven to be quite varied across studies, and most developmental and family scholars today appreciate the great heterogeneity in divorce effects. Thus, this inquiry sought to determine whether select dopaminergic genes previously associated with externalizing behavior and/or found to moderate diverse environmental effects (dopamine receptors D2 and D4, catechol-O-methyltransferase) might moderate divorce effects on adolescent self-reported externalizing problems; and, if so, whether evidence of gene-environment (G * E) interaction would prove consistent with diathesis-stress or differential-susceptibility models of environmental action. Data from the first and third wave of the Dutch Tracking Adolescents' Individual Lives Survey (n = 1,134) revealed some evidence of G * E interaction reflecting diathesis-stress but not differential susceptibility. It is intriguing that some evidence pointed to "vantage sensitivity," which are benefits accruing to those with a specific genotype when their parents remained together, the exact opposite of diathesis-stress. The limits of this work are considered, especially with regard to the conditions for testing differential susceptibility, and future directions are outlined. PMID- 22781864 TI - Life stress, the dopamine receptor gene, and emerging adult drug use trajectories: a longitudinal, multilevel, mediated moderation analysis. AB - This study was designed to examine the prospective relations of life stress and genetic status with increases in drug use. African Americans (N = 399) in rural Georgia (Wave 1 mean age = 17 years) provided three waves of data across 27.5 months and a saliva sample from which the dopamine receptor D4 (DRD4) gene was genotyped. Multilevel growth curve modeling analysis indicated that emerging adults manifested the highest escalations in drug use when they reported high life stress and carried an allele of DRD4 with 7 or more repeats (7 + R allele). In addition, emerging adults who reported high life stress and carried the 7 + R allele evinced the largest increases in two proximal risk factors for drug use: affiliations with drug-using companions and drug use vulnerability cognitions. Furthermore, when the Gene * Environment interaction effects on the increases in affiliations with drug-using companions and vulnerability cognitions were entered into the model forecasting drug use, the Life Stress * DRD4 Status interaction on drug use became nonsignificant in the presence of the risk mechanisms. This finding provides an example of "second generation" Gene * Environment interaction research in which the interaction's effects on proximal risk mechanisms account for its effects on outcomes. PMID- 22781866 TI - Genetic and neurocognitive contributions to the development of psychopathy. AB - An overview is provided of recent twin, molecular genetic, and magnetic resonance imaging studies that are helping to inform a model of developmental vulnerability to adult psychopathy. Although the current evidence base suggests that children with high levels of callous-unemotional traits are genetically and neurocognitively vulnerable to developing psychopathic and antisocial behaviors, existing research also clearly indicates that environmental influences play an important role. One potential implication is that interventions for children with antisocial behavior and callous-unemotional traits may need to be tailored to take into account their distinct pattern of neurocognitive vulnerability, as revealed by developmental neuroimaging studies. Specifically, interventions that pursue punishment-oriented or explicit empathy induction strategies may be less effective with this group of antisocial children. By contrast, preliminary evidence suggests that enhancing positive parenting and parental involvement, as well as applying consistent rewards may represent more promising intervention approaches. PMID- 22781865 TI - Testing multiple levels of influence in the intergenerational transmission of alcohol disorders from a developmental perspective: the example of alcohol use promoting peers and MU-opioid receptor M1 variation. AB - This study examined the interplay between the influence of peers who promote alcohol use and MU-opioid receptor M1 (OPRM1) genetic variation in the intergenerational transmission of alcohol use disorder (AUD) symptoms while separating the "traitlike" components of AUD symptoms from their age-specific manifestations at three ages from emerging adulthood (17-23 years) to adulthood (29-40 years). The results for males were consistent with genetically influenced peer selection mechanisms as mediators of parent alcoholism effects. Male children of alcoholics were less likely to be carriers of the G allele in single nucleotide polymorphism A118G (rs1799971), and those who were homozygous for the A allele were more likely to affiliate with alcohol use promoting peers who increased the risk for AUD symptoms at all ages. There was evidence for women of an interaction between OPRM1 variation and peer affiliations but only at the earliest age band. Peer influences had stronger effects among women who were G carriers. These results illustrate the complex ways in which the interplay between influences at multiple levels of analysis can underlie the intergenerational transmission of alcohol disorders as well as the importance of considering age and gender differences in these pathways. PMID- 22781867 TI - Aggression as an equifinal outcome of distinct neurocognitive and neuroaffective processes. AB - Early onset aggression precipitates a cascade of risk factors, increasing the probability of a range of externalizing and internalizing psychopathological outcomes. Unfortunately, decades of research on the etiological contributions to the manifestation of aggression have failed to yield identification of any risk factors determined to be either necessary or sufficient, likely attributable to etiological heterogeneity within the construct of aggression. Differential pathways of etiological risk are not easily discerned at the behavioral or self report level, particularly in young children, requiring multilevel analysis of risk pathways. This study focuses on three domains of risk to examine the heterogeneity in 207 urban kindergarten children with high levels of aggression: cognitive processing, socioemotional competence and emotion processing, and family context. The results indicate that 90% of children in the high aggression group could be characterized as either low in verbal ability or high in physiological arousal (resting skin conductance). Children characterized as low verbal, high arousal, or both differed in social and emotional competence, physiological reactivity to emotion, and aspects of family-based contextual risk. The implications of this etiologic heterogeneity of aggression are discussed in terms of assessment and treatment. PMID- 22781869 TI - Emotion regulation in children with behavior problems: linking behavioral and brain processes. AB - Past studies have shown that aggressive children exhibit rigid (rather than flexible) parent-child interactions; these rigid repertoires may provide the context through which children fail to acquire emotion-regulation skills. Difficulties in regulating emotion are associated with minimal activity in dorsal systems in the cerebral cortex, for example, the anterior cingulate cortex. The current study aimed to integrate parent-child and neurocognitive indices of emotion regulation and examine their associations for the first time. Sixty children (8-12 years old) referred for treatment for aggression underwent two assessments. Brain processes related to emotion regulation were assessed using dense-array EEG with a computerized go/no-go task. The N2 amplitudes thought to tap inhibitory control were recorded, and a source analysis was conducted. In the second assessment, parents and children were videotaped while trying to solve a conflict topic. State space grids were used to derive two dynamic flexibility parameters from the coded videotapes: (a) the number of transitions between emotional states and (b) the dispersion of emotional states, based on proportional durations in each state. The regression results showed that flexibility measures were not related to N2 amplitudes. However, flexibility measures were significantly associated with the ratio of dorsal to ventral source activation: for transitions, DeltaR 2 = .27, F (1, 34) = 13.13, p = .001; for dispersion, DeltaR 2 = .29, F (1, 35) = 14.76, p < .001. Thus, in support of our main hypothesis, greater dyadic flexibility was associated with a higher ratio of dorsomedial to ventral activation, suggesting that children with more flexible parent-child interactions are able to recruit relatively more dorsomedial activity in challenging situations. PMID- 22781870 TI - Paranoid thinking, suspicion, and risk for aggression: a neurodevelopmental perspective. AB - This article represents an effort to extend our understanding of paranoia or suspicion and its development by integrating findings across clinical, developmental, and neuroscience literatures. We first define "paranoia" or paranoid thought and examine its prevalence across typically and atypically developing individuals and theoretical perspectives regarding its development and maintenance. We then briefly summarize current ideas regarding the neural correlates of adaptive, appropriately trusting interpersonal perception, social cognition, and behavior across development. Our focus shifts subsequently to examining in normative and atypical developmental contexts the neural correlates of several component cognitive processes thought to contribute to paranoid thinking: (a) attention bias for threat, (b) jumping to conclusions biases, and (c) hostile intent attribution biases. Where possible, we also present data regarding independent links between these cognitive processes and aggressive behavior. By examining data regarding the behavioral and neural correlates of varied cognitive processes that are likely components of a paranoid thinking style, we hope to advance both theoretical and empirical research in this domain. PMID- 22781868 TI - Instantiating the multiple levels of analysis perspective in a program of study on externalizing behavior. AB - During the last quarter century, developmental psychopathology has become increasingly inclusive and now spans disciplines ranging from psychiatric genetics to primary prevention. As a result, developmental psychopathologists have extended traditional diathesis-stress and transactional models to include causal processes at and across all relevant levels of analysis. Such research is embodied in what is known as the multiple levels of analysis perspective. We describe how multiple levels of analysis research has informed our current thinking about antisocial and borderline personality development among trait impulsive and therefore vulnerable individuals. Our approach extends the multiple levels of analysis perspective beyond simple Biology * Environment interactions by evaluating impulsivity across physiological systems (genetic, autonomic, hormonal, neural), psychological constructs (social, affective, motivational), developmental epochs (preschool, middle childhood, adolescence, adulthood), sexes (male, female), and methods of inquiry (self-report, informant report, treatment outcome, cardiovascular, electrophysiological, neuroimaging). By conducting our research using any and all available methods across these levels of analysis, we have arrived at a developmental model of trait impulsivity that we believe confers a greater understanding of this highly heritable trait and captures at least some heterogeneity in key behavioral outcomes, including delinquency and suicide. PMID- 22781871 TI - Reconceptualizing antisocial deviance in neurobehavioral terms. AB - We propose that neuroscientific understanding of antisocial behavior can be advanced by focusing programmatic efforts on neurobehavioral trait constructs, that is, individual difference constructs with direct referents in neurobiology as well as behavior. As specific examples, we highlight inhibitory control and defensive reactivity as two such constructs with clear relevance for understanding antisocial behavior in the context of development. Variations in inhibitory control are theorized to reflect individual differences in the functioning of brain systems that operate to guide and inhibit behavior and regulate emotional response in the service of nonimmediate goals. Variations in defensive reactivity are posited to reflect individual differences in the sensitivity of the brain's aversive motivational (fear) system. We describe how these constructs have been conceptualized in the adult and child literatures and review work pertaining to traditional psychometric (rating and behaviorally based) assessment of these constructs and their known physiological correlates at differing ages as well as evidence linking these constructs to antisocial behavior problems in children and adults. We outline a psychoneurometric approach, which entails systematic development of neurobiological measures of target trait constructs through reference to psychological phenotypes, as a paradigm for linking clinical disorders to neurobiological systems. We provide a concrete illustration of this approach in the domain of externalizing proneness and discuss its broader implications for research on conduct disorder, antisocial personality, and psychopathy. PMID- 22781872 TI - Arrested development: the effects of incarceration on the development of psychosocial maturity. AB - Improvements in temperance, perspective, and responsibility are a part of typical development of psychosocial maturity during adolescence. The existing literature suggests that the developmental course of psychosocial maturity is influenced by normative variations in social context, but little is known about how atypical contexts, such as incarceration, influence its development. The study investigates how the development of psychosocial maturity is affected by incarceration, using data from a 7-year longitudinal study of 1,171 adolescent males. We compared the effects of confinement in juvenile facilities with varying degrees of focus on incarceration versus rehabilitation (i.e., secure vs. residential treatment facilities) and tested whether facility quality and age at incarceration moderate the effect of incarceration on psychosocial maturity. The results indicate that incarceration in a secure setting, but not a residential treatment facility, is associated with a short-term decline in temperance and responsibility. The total amount of time incarcerated in a residential treatment facility, but not a secure setting, had a negative effect on the developmental trajectory of psychosocial maturity. Age at incarceration, but not the facility quality, moderated the effect of recent incarceration: older youths were more susceptible to short-term negative effects of recent incarceration in a secure setting, but they also benefited more than younger participants from short-term positive effects of incarceration in a residential treatment setting. Furthermore, youths who perceived their incarceration setting as unsafe evinced a decline in temperance. Future research and policy implications are discussed. PMID- 22781873 TI - Primary and secondary variants of juvenile psychopathy differ in emotional processing. AB - Accumulating research suggests that psychopathy can be disaggregated into low anxious primary and high-anxious secondary variants, and this research may be important for understanding antisocial youths with callous-unemotional traits. Using model-based cluster analysis, the present study disaggregated 165 serious male adolescent offenders (M age = 16) with high scores on the Youth Psychopathic Traits Inventory into primary and secondary variants based on the presence of anxiety. The results indicated that the secondary, high-anxious variant was more likely to show a history of abuse and scored higher on measures of emotional and attentional problems. On a picture version of the dot-probe task, the low-anxious primary variant was not engaged by emotionally distressing pictures, whereas the high-anxious secondary variant was more attentive to such stimuli (Cohen d = 0.71). Although the two groups differed as hypothesized from one another, neither differed significantly in their emotional processing from a nonpsychopathic control group of offending youth (n = 208). These results are consistent with the possibility that the two variants of psychopathy, both of which were high on callous-unemotional traits, may have different etiological pathways, with the primary being more related to a deficit in the processing of distress cues in others and the secondary being more related to histories of abuse and emotional problems. PMID- 22781875 TI - Covert antisocial behavior, peer deviancy training, parenting processes, and sex differences in the development of antisocial behavior during childhood. AB - Two longitudinal studies were used to examine the occurrence and consequences of peer deviancy training during childhood and the relative role of early covert antisocial behavior in risk for antisocial behavior in early adolescence. Peer deviancy training was apparent in a sample of at-risk first grade children, and it showed persistence and increased prevalence across the school year. Peer deviancy training, peer rejection, and unskilled parenting made additive contributions to the development of antisocial behavior during kindergarten and first grade and to antisocial behavior in fourth grade. Skilled parenting partially mitigated the association of peer deviancy training with antisocial behavior for boys. The appearance and growth of covert antisocial behavior was a predictor of fourth grade antisocial for boys and girls, more so than aggressive and overt antisocial behavior. Peer deviancy training and early covert antisocial behavior were key pathways to girls' antisocial behavior in fourth grade, and they complemented the roles of peer rejection and overt antisocial behavior for boys. The relationships of parenting and peer processes to trajectories of antisocial behavior were similar for boys and girls; but boys showed higher levels of antisocial behavior, were more involved in peer deviancy training, and were more likely to experience peer rejection. PMID- 22781874 TI - Reduced activity within the dorsal endogenous orienting of attention network to fearful expressions in youth with disruptive behavior disorders and psychopathic traits. AB - Using behavioral and blood oxygen level dependent (BOLD) response indices through functional magnetic resonance imaging (fMRI), the current study investigated whether youths with disruptive behavior disorders (conduct disorder and oppositional defiant disorder) plus psychopathic traits (DBD + PT) show aberrant sensitivity to eye gaze information generally and/or whether they show particular insensitivity to eye gaze information in the context of fearful expressions. The participants were 36 children and adolescents (ages 10-17 years); 17 had DBD + PT and 19 were healthy comparison subjects. Participants performed a spatial attention paradigm where spatial attention was cued by eye gaze in faces displaying fearful, angry, or neutral affect. Eye gaze sensitivity was indexed both behaviorally and as BOLD response. There were no group differences in behavioral response: both groups showed significantly faster responses if the target was in the congruent spatial direction indicated by eye gaze. Neither group showed a Congruence * Emotion interaction; neither group showed an advantage from the displayer's emotional expression behaviorally. However, the BOLD response revealed a significant Group * Congruence * Emotion interaction. The comparison youth showed increased activity within the dorsal endogenous orienting network (superior parietal lobule and inferior parietal sulcus) for fearful congruent relative to incongruent trials relative to the youth with DBD + PT. The results are discussed with reference to current models of DBD + PT and possible treatment innovations. PMID- 22781876 TI - The impact of a family-centered intervention on the ecology of adolescent antisocial behavior: modeling developmental sequelae and trajectories during adolescence. AB - This study used an experimental, longitudinal field trial involving random assignment to the Family Check-Up (FCU) to explore the social ecology of adolescent antisocial behavior. A sample of 998 youths and their families was followed from early to late adolescence (age 12 to 18-19). In the intervention condition, 115 families (23%) elected to receive the FCU. In general, random assignment to the FCU in middle school was associated with reductions in late adolescence antisocial behavior (age 18-19). Variable-centered analyses revealed that the effects were mediated by reductions in family conflict from early to middle adolescence (age 12-15). The link between family conflict and antisocial behavior in turn was mediated by association with deviant peers at age 17; parental monitoring at age 17 was also influential but did not attain the status of a mediator. Person-oriented analyses suggested that the FCU was associated with declining trajectories of family conflict and rising trajectories of parental monitoring but was not associated with trajectories of deviant peer association. A dual-trajectory analysis indicated that the pathways to adolescent antisocial behavior were myriad and varied, suggesting new directions for developmental and intervention research. PMID- 22781877 TI - Non-medical use of prescription drugs among Mississippi youth: constitutional, psychological, and family factors. AB - OBJECTIVE: The non-medical use of prescription drugs (NMUPD) among youth is a significant public health concern, ranking as the second most frequently used class of drug in youth after marijuana. Given the complex and multiple pathways that may lead to NMUPD in youth, this study examines predictors of NMUPD across constitutional, psychological, and family/peer domains. METHOD: An ethnically diverse sample of 6790 youth in the 6th-12th grades enrolled in public schools throughout Mississippi completed a battery of questionnaires as part of a broader school-based mental health screening initiative in Mississippi (Behavioral Vital Signs Project). RESULTS: The lifetime prevalence rate of NMUPD in our sample was 6.5%. Pain medications were the most commonly used (57%), followed by benzodiazepines (44%), prescription stimulants (e.g., Ritalin, Concerta, Focalin, Dexedrine; 37%), SSRIs (29%), and antipsychotics (24%). Almost a quarter of NMUPD youth used these drugs for 10days or more during the 30-day period prior to completing the survey, and 8% reported daily use. Binary logistic regression analyses revealed that race; grade level; anxiety, mood, and suicide-related symptoms; and substance use involvement significantly increased risk for NMUPD in youth. CONCLUSIONS: NMUPD among youth is a clinically-relevant and multi determined phenomenon. Findings from this study identify factors relevant to understanding youth NMUPD and also highlight the need for additional research and targeted prevention and intervention programs for NMUPD among youth. PMID- 22781878 TI - Risks of major depressive disorder and anxiety disorders among Thais with alcohol use disorders and illicit drug use: findings from the 2008 Thai National Mental Health survey. AB - Little is known about the risks of mood and anxiety disorders among Asians with alcohol use disorders and the effect of illicit drug use in this population. All participants from the 2008 Thai National Mental Health survey (N=17,140) were assessed for current major depressive disorder, anxiety disorders, and alcohol use disorders by using the Mini International Neuropsychiatric Interview (MINI) and were interviewed for illicit drug use within one year prior to their assessment. Logistic regression modeling was used to determine (a) whether alcohol use disorders were associated with major depressive disorder and anxiety disorders and (b) whether the use of illicit drugs increased these associations. Sex, age, marital status, region, and educational level were found to be significantly associated with major depressive disorder and anxiety disorders and were taken into account in the regression analysis. Compared with the general population, individuals with alcohol use disorders alone had significantly increased risks of major depressive disorder (OR 2.49, 95%CI 1.76-3.53 in men and OR 4.09, 95%CI 2.31-7.26 in women) and anxiety disorders (OR 2.21, 95%CI 1.46 3.36 in men and OR 4.34, 95%CI 2.35-8.03 in women). The risks became higher among individuals with both alcohol use disorders and illicit drug use (OR 3.62, 95% CI 1.64-8.01 in men and OR 11.53, 95%CI 1.32-100.65 in women for major depressive disorder, and OR 3.20, 95%CI 1.36-7.51 in men and OR 13.10, 95%CI 1.48-115.60 in women for anxiety disorders). In conclusion, alcohol use disorders were significantly associated with major depressive disorder and anxiety disorders. Illicit drug use was an important factor in increasing these associations, especially in women. Screening for depression, anxiety, and illicit drug use should be done in individuals with alcohol use disorders. PMID- 22781879 TI - A poly(fluorene-thiophene) donor with a tethered phenanthro[9,10-d]imidazole acceptor for flexible nonvolatile flash resistive memory devices. AB - A conjugated poly(fluorene-thiophene) donor and a tethered phenanthro[9,10 d]imidazole acceptor (PFT-PI) was used as the active layer in flexible nonvolatile resistor memory devices with low threshold voltages (+/-2 V), low switching powers (~100 MUW cm(-2)), large ON/OFF memory windows (10(4)), good retention (>10(4) s) and excellent endurance against electric and mechanical stimulus. PMID- 22781880 TI - Electrical tomography using atomic force microscopy and its application towards carbon nanotube-based interconnects. AB - The fabrication and integration of low-resistance carbon nanotubes (CNTs) for interconnects in future integrated circuits requires characterization techniques providing structural and electrical information at the nanometer scale. In this paper we present a slice-and-view approach based on electrical atomic force microscopy. Material removal achieved by successive scanning using doped ultra sharp full-diamond probes, manufactured in-house, enables us to acquire two dimensional (2D) resistance maps originating from different depths (equivalently different CNT lengths) on CNT-based interconnects. Stacking and interpolating these 2D resistance maps results in a three-dimensional (3D) representation (tomogram). This allows insight from a structural (e.g. size, density, distribution, straightness) and electrical point of view simultaneously. By extracting the resistance evolution over the length of an individual CNT we derive quantitative information about the resistivity and the contact resistance between the CNT and bottom electrode. PMID- 22781881 TI - [Urolithiasis risk factors in obese and overweight children]. AB - INTRODUCTION: Childhood obesity is becoming a worldwide epidemic and its metabolic and cardiovascular complications may already be evident at a young age. Several epidemiologic studies in adults have clearly demonstrated that obesity and overweight increase the risk of kidney disease and urolithiasis. AIM OF THE STUDY: The purpose of this study was to evaluate the relationship between overweight and obesity and urolithiasis risk factors in children. MATERIALS AND METHODS: The main kidney stones risk factors in urine such as calcium concentration, oxalate concentration, citrate concentration, pH of urine as well as BRI (Bonn Risk Index) were analyzed in 249 overweight and obese children (study group) and in 281 children with normal weight (control) at the age of 3 to 18 years old. RESULTS: In the study group the mean oxalate concentration was significantly higher than in the control (0.52+/-0.48 vs. 0.26+/-0.12; p <0.05). The mean calcium concentration of overweight/obese patients was higher than that of normal body weight and the difference was close to statistically significant (3.23+/-2.55 vs 2.58+/-1.59; p=0.0537). The mean urine pH in the study group was 6.28+/-0.46 and was significantly lower (p <0.05) than the mean urine pH in the control, witch was 6.40+/-0.47. The mean citrate concentration among overweight/obese patients was significantly lower than in control (431,2+/-309,5 vs. 637,2+/-310,7; p <0.05). CONCLUSIONS: Our results suggest that obesity or overweight at a young age are associated with an increased risk of kidney stones. Weight loss might be explored as a potential treatment to prevent kidney stone formation. PMID- 22781882 TI - [Clinical symptoms at the diagnosis of the craniopharyngioma]. AB - INTRODUCTION: Craniopharyngioma can cause neurological, ophthalmological and endocrine signs and symptoms. AIM OF THE STUDY: Retrospective analysis of symptoms accompanying diagnosis of craniopharyngioma in children. MATERIAL AND METHODS: 10 children and adolescents, 3.75-14.08 years old, median 8.96, treated in our centre in the years 1992-2010, with diagnosis of craniopharyngioma, were included into the study. In the analysis clinical symptoms at the moment of diagnosis, before surgery treatment were taken into consideration. Data from medical histories, physical examination, auxological data, biochemical and hormonal parameters were analyzed. RESULTS: Among 10 patients, 9 had headaches, 4 had experienced vomiting, 2 had symptoms of cranial hypertension, 6 had vision disorders, 8 had endocrine disorders. A decrease of growth rate was observed in 5 children (among 7 with previous anthropometric data), diabetes insipidus in 2, gain of body weight and delayed puberty in 1, and secondary hypothyroidism in 1 patient. Endocrine disorders appeared on average 13 months before diagnosis of craniopharyngioma. Among them the earliest was the decrease of growth rate - on average 23 months before the diagnosis, and the latest diabetes insipidus - 2 months before it. The most frequent symptom - headaches appeared 2 months before the diagnosis. CONCLUSIONS: 1. Endocrine symptoms are early symptoms of craniopharyngioma, which usually appear before neurological, and ophthalmological disorders. 2. Craniopharyngioma may be a cause of growth disorders in children and adolescents, therefore a detailed analysis of height data on growth charts in pediatric patients is very important for the diagnosis. PMID- 22781883 TI - [The developmental changes in physiological cost of locomotion efforts in overweight boys]. AB - INTRODUCTION: In obese children the aerobic capacity (maximal oxygen intake) is lower than in non-obese children, but lower ability to perform long-term efforts can also result from higher physiological cost (in comparison to normal weight children) during locomotion efforts. AIM OF THE STUDY: was to determine developmental changes in physiological cost of walks in boys with excessive level of body fat (F%) during puberty. MATERIAL AND METHODS: The study was conducted on 11 boys with excessive level of body fat (%F=26.82+/-2.89 % - GROUP O) and 14 with normal level of body fat (%F=12.51+/-2.35% - GROUP P). The boys performed the graded test and a few days later two submaximal walks (6 min each with a 4 min pause for rest between walks) on mechanical treadmill with different speed (3.6 km*h(-1) and 4.8 km*h(-1)) every two years (three series) beginning at the age about 10 years and finishing at the age of 13-14 years. RESULTS: The level of pulmonary ventilation (VE) and tidal volume (TV) were significantly higher in overweight boys, but breathing frequency (BF) was similar in both groups. With age, the economy of breathing was improved in both groups: pulmonary ventilation and tidal volume were increasing but BF was decreasing. The work intensity during walking, expressed as %VO2max and %HRmax, was higher in boys with excessive level of body fat and decreased with age. Total values of VO2 (l*min(-1)) were higher in the group of overweight boys, but relatively to body mass the values of VO2 were significantly lower in this group and with age the difference between groups was constant. CONCLUSIONS: The physiological cost of walking was higher in boys with excessive level of body fat in each test in comparison with non-obese boys. The difference between groups in level of physiological parameters increased with speed of walking. The physiological cost of walking decreased with age in both groups. PMID- 22781884 TI - [Changes in structure and socioeconomic position of the family as determinants of overweight in adolescents]. AB - INTRODUCTION: Previous studies on relationships between the current family structure, socioeconomic status and family members' body mass don't give unequivocal results. A life course perspective evaluates the contribution of early life factors jointly with later life factors to identify risk and protective processes. OBJECTIVES: The relationship between economic status, family structure in first and thirteenth year of life, their changes in this period and overweight among 13-year olds in Poland. PARTICIPANTS AND METHODS: A study sample was the prospective cohort of 11 937 children enrolled in the observation in neonatal period, examined in the third year of life (questionnaire survey of 1250 mothers) and at the age of thirteen (561 children and their parents fulfilled questionnaires, children's height and weight were measured). Overweight criteria was BMI >85 percentile using WHO 2007 growth reference. RESULTS: Higher prevalence of overweight was found in adolescents living in single-parent families than in 2-parent families (30.2% vs. 19.5%; p=0.049). The highest prevalence of adolescents' overweight was observed in families, whose structure changed during 13 years (in ""broken"" families - 32.7%, in reconstructed - 36.4%, p=0.033); the risk of overweight in these children increased twice compared to intact families. Adolescents from families whose reported economic status worsened during 13 years, were twice more likely to be overweight than their peers from middle and high economic status families (p=0.057). CONCLUSIONS: The prevalence of overweight among adolescents in 2 parent families is significantly lower than in other family types. Unfavorable changes in family economic status and structure are the strongest redictors of overweight in 13-year-olds. PMID- 22781885 TI - [Selective immunoglobulin A deficiency]. AB - Immunoglobulin class A is the main protein of the mucosal immune system. Selective immunoglobulin A deficiency (sIgAD) is the most common primary immunodeficiency in Caucasians. sIGAD is strongly associated with the certain major histocompatibility complex region. Most individuals with sIgAD are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections, allergic disorders and autoimmune manifestations. Several autoimmune diseases, such as systemic lupus erythematosus, diabetes mellitus type 1, Graves disease and celiac disease, are associated with an increased prevalence of sIgAD. Screening for sIgAD in coeliac disease is essential. Patients need treatment of associated diseases. It is also known that IgA deficiency may progress into a common variable immunodeficiency (CVID). Pathogenesis and molecular mechanism involved in sIgAD should be elucidated in the future. PMID- 22781887 TI - [Novel pathogenesis-oriented strategies for the management of primary immune thrombocytopenia]. PMID- 22781886 TI - [Probiotics and prebiotics as a bioactive component of functional food]. AB - The results of food science investigations have confirmed the relationship between the type of eaten food and health. Simultaneously, consumers are paying more and more attention to the kind of food they eat, as their awareness concerning the influence of proper food on health is increasing. On that base the conception of functional food has been created. This kind of food, besides being a source of essential macro- and micronutrients, exerts an additional positive influence on health. Probiotics and prebiotics containing products are a good example of functional food. These products provide not only essential nutrients but also microorganisms and polysaccharides, which are indigestible in the human alimentary tract, but exert a positive effect on human health. It may be a therapeutic or prophylactic effect due to specific affliction or may improve health in general. The paper - based on available literature - shows a positive influence of probiotics and prebiotics on human health, especially in the immunomodulation effect, an advantageous effect on the digestive system, antitumor activity and a possible therapeutic and prophylactic effect on cardiovascular diseases and obesity. PMID- 22781888 TI - [Etiological analysis of fever in the first 24 hours following allogeneic peripheral stem cell transfusion]. AB - OBJECTIVE: To investigate the incidence and pathogenesis of fever within the first 24 hours following allogeneic peripheral stem cell transfusion and to analyze the associated risk factors. METHODS: Totally 114 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) between October 2009 and August 2010 were enrolled and clinical data of febrile patients within 24 hours following peripheral stem cell transfusion were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify the risk factors for transfusion related fever. RESULTS: Thirty-two (28.1%) out of the 114 patients had a fever within 24 hours after allo-HSCT. All of them were human leukocyte antigen (HLA) mismatch transplantation. The median time of the temperature elevated was 2.5 (0 - 18.0) hours after the infusion with a median time of the peak of 7.8 (3.5 - 23.0) hours after the infusion. Fever was attributed to definite infection in 6 patients and no definite infection in the remaining 26 patients. None of them were hemolytic, which was attributed to transfusion related fever. Multivariate analysis showed that female donor and high count of peripheral leukocyte of donor peripheral blood were significant predictors for transfusion related fever. CONCLUSIONS: Most of post-infusion fever within 24 hours after HLA mismatch related transplantation has no identifiable infectious focus. The risk factors for transfusion related fever are female donor and high number of peripheral leukocyte of donor blood. PMID- 22781889 TI - [A clinical analysis of AIDS-related non-Hodgkin lymphoma in 5 patients and review of literature]. AB - OBJECTIVE: To analyze the clinical characteristics of AIDS-related non-Hodgkin lymphoma (ARL) and review relative literature for the diagnosis and treatment of ARL. METHOD: The clinical data of ARL patients admitted to Peking Union Medical College Hospital from April 2009 to April 2011 were retrospectively analyzed. RESULTS: Five male ARL patients aged 32 to 65 years old were included in this retrospective study. Among them, two patients were found to be HIV-positive for the first time, three were on regular highly active anti-retroviral therapy (HAART) for 7 - 8 months before the emergence of lymphoma-related symptoms. CD(4)(+) T cell count was (69 - 232) * 10(6)/L at presentation. Two patients firstly presented with sore throat and throat ulcer, one with cervical nodules, one with pelvic mass, one with fever and edema in right thigh. Through pathological analysis, four patients had B cell-originated lymphoma, with one Burkitt lymphoma and three diffuse large B cell lymphomas; one patient had T-cell lymphoma. Four patients were treated with chemotherapy, with one complete remission, one relapse, one non-response, and one death. One patient had radiotherapy only and had progressed disease. Bone marrow suppression and gastrointestinal disturbance were the main adverse effects of chemotherapy. CONCLUSIONS: Lymphoma should be considered in any HIV-infected patients presented with unexplainable adenopathy, recurrent sore throat or throat ulcer, or fever of unknown origin. Biopsy should be rigorously carried out. Appropriate chemotherapy, together with HAART, may improve the prognosis greatly. PMID- 22781890 TI - [The efficacy and safety of autologous cryopreserved platelet transfusion in management of thrombocytopenia after chemotherapy in hematological malignancy]. AB - OBJECTIVE: To investigate the efficacy and safety of autologous cryopreserved platelet transfusion in the management of thrombocytopenia after chemotherapy in hematological malignancy. METHODS: A total of 40 patients diagnosed as hematological malignancy with complete remission were equally assigned into study group and control group. During chemotherapy interval in the study group, when platelet counts exceeded 120 * 10(9)/L, autologous platelets were collected with CS3000 Cell Separator and cryopreserved at -80 degrees C with 5% dimethylsulfoxide. When platelet counts dropped below 15 * 10(9)/L after chemotherapy, autologous platelets were thawed with 40 degrees C water bath and transfused back to each patient. In the control group, when platelet counts dropped below 15 * 10(9)/L after chemotherapy, allogeneic fresh platelets were transfused. Median loss during the freeze-thaw-wash procedure in study group was observed, and the 1 h, 24 h corrected count increments (CCI) were calculated in the both groups. The hemostatic effects and adverse reactions were also observed. RESULTS: In the control group, 1hCCI and 24h CCI were (19.3 +/- 6.1) * 10(9)/L and (12.2 +/- 7.0) * 10(9)/L, respectively, with the effective rate of 80% and the transfusion reaction rate of 45%. Totally 20 collection and transfusions were finished in the study group. A total of (3.4 - 8.5) * 10(11) platelet were obtained in each collection. Platelet recovery after freezing and thawing was (73.51 +/- 9.03)% (62% - 83%). 1hCCI was (17.4 +/- 7.6) * 10(9)/L, 24h CCI was (10.5 +/- 5.8) * 10(9)/L and the effective rate was 85%. There was no significant different between the two groups (P > 0.05). The transfusion reaction rate was 15%, which was significantly lower than that of the control group (P < 0.05). Meanwhile, adverse reactions were occurred less in the study group. CONCLUSION: This study demonstrates that autologous cryopreserved platelet transfusions can be safely administered for supporting thrombocytopenia in hematological malignancy patients undergoing chemotherapy. PMID- 22781891 TI - [The value of procalcitonin for diagnosing infection in critically ill patients receiving long-term immunosuppressive therapy]. AB - OBJECTIVE: To assess the value of procalcitonin (PCT) measurement to differentiate infection from non-infection in critically ill patients requiring long-term immunosuppressive therapy. METHODS: A prospective study was conducted in patients with underlying diseases requiring corticosteroids or chemotherapy in ICU from January 2008 to December 2009. Patients were divided into the infection group and the non-infection group and their PCT levels were compared. RESULTS: A total of 103 patients (65 women) were enrolled in this prospective study [aged (47.9 +/- 21.9) years old] with 84 in the infection group and 19 in the non infection group. The baseline level of PCT was significantly higher in infection than in non-infection patients [2.58 (0.08 - 44.65) pg/L vs 0.62 (0.15 - 6.00) pg/L, P = 0.002]. Different levels of PCT were manifested in different pathogen groups with 3.41 (0.45 - 44.65) pg/L in bacteria infection, 0.99 (0.28 - 6.67) pg/L in fungus infection, 0.11 (0.08 - 0.20) pg/L in virus infection group (P = 0.018). The AUC(ROC) of PCT was 0.867 for diagnostic bacterial infection. By multivariate analysis, the factors associated with the level of PCT were bacteria infection (OR 5.1, P = 0.031) and septic shock (OR 7.5, P = 0.027), while the factors not associated with the level of PCT were age, renal function, infection site and prognosis (P > 0.05). CONCLUSIONS: The level of PCT is increased in the critically ill patients requiring immunosuppressive therapy with infection and it can be used for diagnosis for bacterial infection. PMID- 22781892 TI - [The relationship between oxidative stress and endothelial progenitor cells count in the first-degree relatives of diabetes mellitus]. AB - OBJECTIVE: To study the relationship between oxidative stress and endothelial progenitor cells (EPCs) count in the first-degree relatives of diabetes mellitus (FDRs). METHODS: Three groups were evaluated with 40 type 2 diabetes mellitus (T2DM) patients, 38 FDRs and 30 healthy individuals as the control (NC). Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), TG, TC and fasting plasma insulin concentrations were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was calculated. Quantity of EPCs and flow-mediated dilation (FMD) were evaluated. Malonaldehyde (MDA), glutathion peroxidase (GSH-Px), erythrocuprein (SOD) and total anti-oxidative capacity (TAO-C) were measured. RESULTS: In T2DM group FPG [(7.86 +/- 0.77) mmol/L] and HbA1c [(7.24 +/- 0.20) %] were significantly higher than those in NC [FPG (4.90 +/- 0.35) mmol/L, HbA1c (5.34 +/- 0.37)%] and FDRs group [FPG (5.13 +/- 0.95) mmol/L, HbA1c (5.36 +/- 0.36)%] (all P values < 0.05). TC in T2DM group [(5.88 +/- 0.76) mmol/L] was higher than in NC [(4.66 +/- 0.90) mmol/L] and FDRs [(4.95 +/- 0.76) mmol/L]. HOMA-IR was 0.48 +/- 0.25 in NC, 0.81 +/- 0.46 in FDRs and 1.47 +/- 0.24 in T2DM group, P < 0.01. In T2DM group, the plasma levels of SOD [(69.30 +/- 2.21) U/ml], TAO-C [(7.30 +/- 0.29) U/ml] and GSH-Px [(856.5 +/- 9.01) U/ml] were significantly lower than those in NC [SOD (75.33 +/- 3.63) U/ml, TAO-C (8.17 +/- 0.58) U/ml and GSH-Px (938.1 +/- 19.35) U/ml] and FDRs group [SOD (74.91 +/- 4.53) U/ml, TAO-C (8.24 +/- 0.46) U/ml and GSH-Px (936.9 +/- 15.78) U/ml] (all P values < 0.01). Serum level of MDA was (2.87 +/- 0.63) umol/L in NC, (3.28 +/- 0.71) umol/L in FDRs and (3.69 +/- 0.39) umol/L in T2DM group (P < 0.01). The quantity of EPCs and FMD% were 96.75 +/- 8.11 and 8.36 +/- 2.21 in NC, 83.34 +/- 12.43 and 6.78 +/- 0.98 in FDRs and 58.45 +/- 7.58 and 2.86 +/- 0.35 in T2DM group with statistical differences between different groups (all P values < 0.05). Pearson correlation analysis showed that lnHOMA-IR was positively correlated with MDA (r = 0.486, P < 0.05) and negatively correlated with SOD, TAO C, GSH-Px (r = -0.426, -0.601, -0.524, all P values < 0.05) in FDRs group. CONCLUSIONS: Insulin resistance, oxidative stress, decreased quantity of EPCs and impairment of endovascular function have already occurred in the FDRs of T2DM with normal glucose tolerance and they are correlated with each other. PMID- 22781893 TI - [An analysis of stroke subtypes and influencing factors in different regions of China]. AB - OBJECTIVE: To analyze the stroke subtypes and influencing factors in four largest economic regions of China. METHODS: We analyzed the investigation data of QUEST (Quality Evaluation of Stroke Care and Treatment) study conducted in 2006 which included 62 hospitals in a national scale. According to the concept of four economic regions designed by the Development Research Center of the State Council, we performed the univariate and multivariate analysis for the stroke subtypes and its related risk factors in the different economic regions. RESULTS: There were 3362 (73.5%) ischemic stroke patients and 1214 (26.5%) hemorrhagic stroke patients among the total 4576 first-ever stroke patients. Comparison of stroke subtypes in the four different economic regions was statistically significant (P < 0.001), with a percentage of 80.8% ischemic stroke patients in the northeastern region, 78.9% in the eastern region, 68.3% in the central region and 67.0% in the western region. The comparisons of risk factors such as history of hypertension, diabetes, hyperlipidaemia, coronary artery event, atrial fibrillation, and overweight in the four different economic regions were also statistically significant (P < 0.05). CONCLUSIONS: The subtypes of first-ever stroke vary in the four largest economic regions with a highest proportion of ischemic stroke in the northeastern region and relatively high proportion of hemorrhagic stroke in the central and western economic regions. There are also discrepancies of stroke risk factors in the different economic regions. PMID- 22781894 TI - [The value of ankylosing spondylitis disease activity score in evaluating disease activity of ankylosing spondylitis]. AB - OBJECTIVE: To investigate the value of ankylosing spondylitis (AS) disease activity score (ASDAS) and the Bath AS disease activity index (BASDAI) in evaluating disease activity in AS. METHODS: ASDAS and BASDAI were used to evaluate disease activity in patients with AS, taking the patients' global scores, physician global scores and treatment decision as the "gold standard" for disease activity. According to the "gold standard", the patients were divided into low and high disease activity groups. Statistical analysis included descriptive statistics, linear correlation and regression and ROC curve. RESULTS: A total of 227 patients with AS were included. ASDAS and BASDAI showed good correlation with disease activity as reflected by the patients' global score [r for BASDAI, ASDAS based on ESR(ASDAS-ESR) and ASDAS based on C-reactive protein (ASDAS-CRP) were 0.713, 0.698 and 0.725, respectively, P = 0.000] and the physician global score (r for BASDAI, ASDAS-ESR and ASDAS-CRP were 0.771, 0.782, 0.847, respectively, P = 0.000). Both scores showed good discriminative ability for high and low disease activity states. ASDAS-CRP had the highest sensitivity. CONCLUSION: ASDAS is a promising tool for evaluating disease activity in AS patients. PMID- 22781895 TI - [The levels and clinical significance of serum B cell activating factor in Chinese patients with polymyositis or dermatomyositis]. AB - OBJECTIVES: To investigate serum levels of B cell activating factor (BAFF) in Chinese patients with polymyositis (PM) or dermatomyositis (DM), and analyze the correlation of BAFF with autoantibodies and clinical phenotypes. METHODS: Serum BAFF levels of 28 PM patients and 30 DM patients (study group), and 25 matched healthy controls (control group) were measured by ELISA. Serum anti-Jo-1 antibody levels were also measured by ELISA in all the subjects. The results of the two groups were compared by unpaired t test and the relevance was analyzed by Pearson's correlation analysis. RESULTS: Serum levels of BAFF in PM/DM patients were significantly higher compared to healthy controls (P = 0.000), but there was no statistically significant difference between the PM and DM patients (P > 0.05). Patients with interstitial lung disease (ILD) had significantly higher serum BAFF level than the patients without ILD (P = 0.000) or the controls (P = 0.000). Serum BAFF levels of patients with positive anti-nuclear antibody (ANA) were significantly higher than those with negative ANA (P = 0.003). For patients with anti-Jo-1 antibodies, the serum BAFF levels were correlated with the serum concentration of anti-Jo-1 antibodies (r = 0.799, P = 0.006). CONCLUSIONS: Serum levels of BAFF are increased in Chinese PM/DM patients. These findings indicate that BAFF may be possibly enrolled in the pathogenesis of PM/DM. Detecting serum BAFF levels could have some implication for the diagnosis and treatment of PM/DM. PMID- 22781896 TI - [A clinical analysis of dermatomyositis with interstitial lung disease in 20 patients]. AB - OBJECTIVE: To investigate the clinical features of the patients with dermatomyositis (DM) complicated with interstitial lung disease (ILD). METHODS: The clinical manifestations and the laboratory data of the 20 patients with DM complicated with ILD were retrospectively analyzed. RESULTS: Among 169 DM patients, 20(11.8%) were founded with ILD and 4 had no complaint of respiratory system. The ratio of male to female was 1:2.33. The level of serum creatine kinase (CK) was elevated in 11 cases. Anti-Jo-1 antibody was positive in 4 cases. Bilateral infiltrates including ground-glass attenuation, interlobular septal thickening and reticular opacities were found by chest high resolution computed tomography. The impairment of lung function was manifested as the decreased diffusion capacity for carbon monoxide of the lung (D(L)CO) and restricted ventilatory function abnormalities. Fifteen cases showed hypoxemia or respiratory failure by arterial blood gas analysis. All patients were treated with glucocorticoid and/or immunosuppressive agents. Totally, 14 patients had improved, while 2 patients with no improvement and 4 patients died with a mortality of 20%. CONCLUSIONS: DM complicated with ILD which is easily missed has a high morbidity and mortality. The understanding of DM complicated with ILD should be enhanced, thus early diagnosis and intervention could be performed for better prognosis. PMID- 22781897 TI - [Radiological imaging in evaluation of etiologies for cerebral infarction after non-cardiac surgeries]. AB - OBJECTIVE: To investigate the pathogenesis of cerebral infarction after non cardiac surgeries according to imaging. METHODS: Retrospective analyses of clinical and imaging data of 17 patients with postoperative cerebral infarction (average 68 years old, total incidence 0.049%) from departments of orthopedics and general surgery were conducted during 52 months. RESULTS: Cerebral infarction occurred 39.1 hours after operation on average. Among the 17 patients, eight were detected with disturbance of consciousness, ten with hemiplegia, six with speech disorder and two with unilateral sensory disturbance. Six (35.3%) had blood lipids tests. Five (29.4%) had neck vascular ultrasound and one had intracranial magnetic resonance angiography (MRA). When discharged, one patient was declared death and ten had impaired neurological function in various degrees. Among six patients with previous stroke, one (16.7%) received neurological consultation before surgery. According to the image manifestation, ten cases were territory circulation infarcts, four centrum ovale infarcts and three watershed infarcts. CONCLUSIONS: This study suggests that total incidence of cerebral infarction after non-cardiac surgeries is lower than previously reported and there is greater involvement of atherosclerosis. Patients' conditions should be closely observed within at least four days after surgeries. Preoperative assessment should be strengthened in order to avoid occurrence of postoperative cerebral infarction. PMID- 22781898 TI - [The expression and clinical significance of SphK1 and nuclear factor-kappaB p65 in human colon carcinoma]. AB - OBJECTIVE: To investigate the expression of sphingosine kinase 1 (SphK1) and NF kappaB in colon carcinoma tissues and their correlation with clinicopathologic features. METHODS: Sixty-six paraffin-embedded colon carcinoma samples and 66 fresh colon carcinoma samples were tested using immunohistochemistry, RT-PCR and Western blot, respectively. RESULTS: In 66 fresh colon carcinoma samples, the positive rate of SphK1 and NF-kappaB mRNA expression were 84.85%(56/66) and 74.24% (49/66), while the positive rate of SphK1 and NF-kappaB protein detected by Western blot were 78.79% (52/66) and 69.70% (46/66). The positive rates were higher than those in the adjacent tissues [mRNA: 63.64% (42/66), 48.49% (32/66); protein: 57.58% (38/66), 45.45% (30/66)] and the normal mucosa [mRNA: 42.42% (28/66), 25.76% (17/66); protein: 36.36% (24/66), 24.24% (16/66)], with statistical significances (all P values < 0.05). The mean expressive levels of SphK1 and NF-kappaB mRNA and protein in colon carcinoma were both significantly higher than those in the adjacent tissues and the normal mucosa (mRNA: 0.55 +/- 0.06 vs 0.35 +/- 0.05 vs 0.25 +/- 0.05, 0.75 +/- 0.06 vs 0.43 +/- 0.05 vs 0.30 +/ 0.04; protein: 0.77 +/- 0.05 vs 0.38 +/- 0.06 vs 0.12 +/- 0.03, 0.45 +/- 0.08 vs 0.23 +/- 0.05 vs 0.13 +/- 0.03; all P values < 0.05). There was a close correlation between SphK1 and NF-kappaB expression levels (r = 0.459, P = 0.036). The results of immunohistochemistry were similar to those of RT-PCR and Western blot. Overexpression of SphK1 and NF-kappaB in colon carcinoma was related with depth of invasion, distant and lymph node metastasis and Dukes' stages (all P values < 0.05). The expression of SphK1 was also related with differentiation (P < 0.05). CONCLUSIONS: Overexpression of SphK1 and NF-kappaB may be involved in the pathogenesis and progression of colon carcinoma. Moreover, SphK1 and NF kappaB may be correlated with the invasion and metastasis of colon carcinoma. PMID- 22781899 TI - [The effects of Guanxinshutong on protection of left ventricular function after acute myocardial infarction in rats]. AB - OBJECTIVE: To assess the effects of Guanxinshutong capsule (GXST) on protection of left ventricular (LV) function after acute myocardial infarction (AMI) in rats. METHODS: Twenty-eight male Sprague Dawley rats were randomized to Model group, Drug group and Sham-operated group, with acute myocardial infarction (AMI) achieved by ligating coronary artery in Model and Drug groups. From one week before surgery to four weeks after surgery, GXST for Drug group (1.5 g/kg, 2 times/day) or saline for Model and Sham-operated groups was administered via direct gastric gavage. After four weeks of treatment following surgery, measurement of LV function, pathohistological observation and analysis were performed. RESULTS: Compared with rats in the Model group, LV systolic pressure (LVSP) [(97.7 +/- 9.0) mm Hg (1 mm Hg = 0.133 kPa) vs (85.9 +/- 9.4) mm Hg], the maximum rising rate of LV pressure (+dp/dtmax) [(4810.2 +/- 595.0) mm Hg/s vs (3786.2 +/- 723.0) mm Hg/s] and the maximum dropping rate of LV pressure ( dp/dtmax) [(3781.6 +/- 573.6) mm Hg/s vs (2774.4 +/- 633.5)mm Hg/s] in the Drug group were significantly increased, while LV end-diastolic pressure (LVEDP) [(10.3 +/- 0.7) mm Hg vs (12.7 +/- 2.4) mm Hg] in the Drug group was significantly decreased (all P < 0.05). Myocardial pathohistological morphology was improved in the Drug group with fibrosis alleviated [(5.13 +/- 1.37)% vs (7.27 +/- 1.01)%] and infarct size reduced [(20.14 +/- 8.49)% vs (31.90 +/- 4.98)%]. Apoptosis index (AI) was decreased [(14.05 +/- 4.04)% vs (20.87 +/- 6.03)%] and vessel density was significantly increased by 1.48-fold in the Drug group (all P < 0.05). CONCLUSIONS: GXST is effective in protecting LV function after AMI in rats, which may be affect through increasing vessel density of infarction area, improving myocardial pathohistological morphology, alleviating fibrosis, reducing infarct size and decreasing AI. PMID- 22781901 TI - Protein evolution: keeping BUBR1 intact. PMID- 22781900 TI - New lives for old: evolution of pseudoenzyme function illustrated by iRhoms. AB - Large-scale sequencing of genomes has revealed that most enzyme families include inactive homologues. These pseudoenzymes are often well conserved, implying a selective pressure to retain them during evolution, and therefore that they have significant function. Mechanistic insights and evolutionary lessons are now emerging from the study of a broad range of such 'dead' enzymes. The recently discovered iRhoms - inactive homologues of rhomboid proteases - have joined derlins and other members of the rhomboid-like clan in regulating the fate of proteins as they pass through the secretory pathway. There is a strong case that dead enzymes, which have been rather overlooked, may be a rich source of biological regulators. PMID- 22781902 TI - Chromatin: RNA eviction by HP1. PMID- 22781903 TI - Orchestrating vesicle transport, ESCRTs and kinase surveillance during abscission. AB - During the final stage of cell division, the future daughter cells are physically separated through abscission. This process requires coordination of many molecular machines, including endocytic and secretory vesicle trafficking proteins as well as ESCRT (endosomal sorting complex required for transport) proteins, that mediate a complex series of events to culminate in the final separation of daughter cells. Abscission is coordinated with other cellular processes (for example, nuclear pore reassembly) through mitotic kinases such as Aurora B and Polo-like kinase 1, which act as master regulators to ensure proper progression of abscission. PMID- 22781904 TI - Cell death: multitasking p53 promotes necrosis. PMID- 22781906 TI - Current controversies in fluid resuscitation in acute pancreatitis: a systematic review. AB - Acute pancreatitis (AP) is a common inflammatory disorder of the pancreas resulting in considerable morbidity and mortality. Aggressive intravenous fluid resuscitation generally is recommended in all patients with AP and remains the cornerstone of management of these patients. However, the optimal rate, type, and the goal of resuscitation remain unclear. The purpose of this review was to give an insight about the pathophysiologic alterations in the pancreatic microcirculation that occur in AP, the markers for early recognition of severity of pancreatitis, the optimal fluid, and timing and extent of fluid resuscitation. An early elevated hematocrit, blood urea nitrogen, or creatinine should prompt clinicians to institute more intensive early resuscitation measures. Crystalloids are the currently recommended fluids for management of these patients. Current studies are underway to determine the optimal end points of fluid resuscitation that determine outcome. PMID- 22781905 TI - H2S signalling through protein sulfhydration and beyond. AB - Hydrogen sulfide (H(2)S) has recently emerged as a mammalian gaseous messenger molecule, akin to nitric oxide and carbon monoxide. H(2)S is predominantly formed from Cys or its derivatives by the enzymes cystathionine beta-synthase and cystathionine gamma-lyase. One of the mechanisms by which H(2)S signals is by sulfhydration of reactive Cys residues in target proteins. Although analogous to protein nitrosylation, sulfhydration is substantially more prevalent and usually increases the catalytic activity of targeted proteins. Physiological actions of sulfhydration include the regulation of inflammation and endoplasmic reticulum stress signalling as well as of vascular tension. PMID- 22781907 TI - Lymph node sampling rates and predictors of nodal metastasis in pancreatic neuroendocrine tumor resections: the UCSF experience with 149 patients. AB - OBJECTIVES: The decision to perform pancreas-preserving procedures or standard resections for pancreatic neuroendocrine tumors (PNETs) is often based on the perceived risk of malignancy, including potential nodal involvement. We sought to identify clinicopathological factors that predict nodal disease. METHODS: This is a retrospective review of pathology database for PNET resections from January 1, 1988, to March 15, 2010. Univariate analysis and multivariate logistic regression were used to identify predictors of nodal metastasis. RESULTS: A total of 149 patients were identified. Enucleations had lower lymph node sampling rates compared to major resections. Excluding enucleations, 23% of patients had no lymph nodes sampled. For patients who did have lymph nodes evaluated, a median of 5 lymph nodes were examined. On multivariate analysis, only distant disease predicted nodal metastasis (odds ratio = 3.80, P = 0.02); tumor size did not (P = 0.48). One third of patients with lymph node metastasis had tumors less than 3 cm. CONCLUSIONS: Lymph nodes are not evaluated in many major pancreatic resections for PNET, and preoperative prediction of nodal metastasis is difficult, even when tumor size is considered. Consequently, many patients may be understaged and undergo potentially inadequate resection. Inconsistent lymph node sampling may explain conflicting conclusions in the literature regarding the prognostic value of lymph node involvement in PNET patients. PMID- 22781908 TI - Development of a novel model of hypertriglyceridemic acute pancreatitis in hamsters: protective effects of probucol. AB - OBJECTIVES: The aim of the present study was to develop a model of hypertriglyceridemic (HTG) acute pancreatitis and to investigate the effects of probucol in this model. METHODS: Hamsters were fed a high-fat diet (HFD) or a normal diet for 3 weeks. Probucol was added at 1% to the HFD in the treated group. Pancreatitis was induced by 7 peritoneal injections of cerulein to the normal and HFD hamster groups. The severity of the pancreatitis and whole body oxidative stress were assessed. RESULTS: The HFD induced severe HTG (>1000 mg/dL) in the hamsters. A more severe pancreatitis was observed in the HFD group. The HFD did not influence plasma-reduced glutathione level, but there was a significant increase after 1% probucol was provided in the diet. Plasma malonaldehyde levels in the HFD group were significantly higher than the normal chow group, whereas probucol administration significantly decreased plasma hydrogen peroxide and malonaldehyde levels. We also found that probucol significantly reduced levels of amylase and lipase in the plasma and pathological scores in pancreatic tissue. CONCLUSIONS: This study presents a novel model of severe HTG acute pancreatitis, and our results support the potential therapeutic application of probucol in HTG acute pancreatitis. PMID- 22781909 TI - Histological loss of pancreatic exocrine cells correlates with pancreatic exocrine function after pancreatic surgery. AB - OBJECTIVE: The aim of this study was to investigate the relationship between histological findings of the pancreatic stump and postoperative pancreatic exocrine function. METHODS: One hundred ten patients including 80 patients undergoing pancreatoduodenectomy (PD) and 30 patients undergoing distal pancreatectomy (DP) were enrolled into this study. Postoperative exocrine pancreatic function was evaluated by 13C-labeled mixed triglyceride breath test. The areas of acinar cells, fibrotic tissues, and fatty replacement were histologically calculated in surgical specimens of the pancreatic stump. RESULTS: Histologically, acinar cell area of patients undergoing PD was significantly less than that of patients undergoing DP (P = 0.025). The values of the mean percentage dose 13C cumulative 7 hours of patients undergoing PD were significantly lower than those of patients undergoing DP (P < 0.001). The rate of pancreatic exocrine insufficiency in patients undergoing PD is significantly higher than that in patients with DP (P = 0.002). There was a significant correlation between acinar cell area of the pancreatic stump and the percentage dose 13C cumulative 7 hours (R = 0.35, P < 0.001). CONCLUSIONS: Pancreatoduodenectomy induced pancreatic exocrine insufficiency more frequently than DP. Histological loss of acinar cells in the pancreatic stump was strongly correlated with postoperative pancreatic exocrine function. PMID- 22781910 TI - Combination of CFTR gene mutation and autoimmune pancreatitis presenting as necrotizing pancreatitis. PMID- 22781911 TI - The occurrence of islet amyloid polypeptide amyloidosis in Japanese subjects. PMID- 22781912 TI - FOLFIRINOX in locally advanced pancreatic cancer: the starting point for questioning. PMID- 22781913 TI - Hypoglycemia after simultaneous pancreas-kidney transplant: fact or factitious? PMID- 22781914 TI - Circulating lymphocyte subsets in pancreatic adenocarcinoma and their relationship to the stage of the disease. PMID- 22781915 TI - Feasibility of second-generation transabdominal ultrasound-elastography to evaluate solid pancreatic tumors: preliminary report of 36 cases. PMID- 22781916 TI - President William McKinley (1843-1901): the first reported case of traumatic gunshot pancreatitis. PMID- 22781917 TI - Nafamostat mesilate-induced hepatocellular necrosis in a child with pancreatitis caused by pancreaticobiliary maljunction: drug-induced liver injury. PMID- 22781918 TI - Minimizing the dependency ratio in a population with below-replacement fertility through immigration. AB - Many industrialized countries face fertility rates below replacement level, combined with declining mortality especially in older ages. Consequently, the populations of these countries have started to age. One important indicator of age structures is the dependency ratio which is the ratio of the nonworking age population to the working age population. In this work we find the age-specific immigration profile that minimizes the dependency ratio in a stationary population with below-replacement fertility. It is assumed that the number of immigrants per age is limited. We consider two alternative policies. In the first one, we fix the total number of people who annually immigrate to a country. In the second one, we prescribe the size of the receiving country's population. For both cases we provide numerical results for the optimal immigration profile, for the resulting age structure of the population, as well as for the dependency ratio. PMID- 22781919 TI - Mesoporous bioactive glass scaffolds for efficient delivery of vascular endothelial growth factor. AB - In this article, we, for the first time, investigated mesoporous bioactive glass scaffolds for the delivery of vascular endothelial growth factor. We have found that mesoporous bioactive glass scaffolds have significantly higher loading efficiency and more sustained release of vascular endothelial growth factor than non-mesoporous bioactive glass scaffolds. In addition, vascular endothelial growth factor delivery from mesoporous bioactive glass scaffolds has improved the viability of endothelial cells. The study has suggested that mesopore structures in mesoporous bioactive glass scaffolds play an important role in improving the loading efficiency, decreasing the burst release, and maintaining the bioactivity of vascular endothelial growth factor, indicating that mesoporous bioactive glass scaffolds are an excellent carrier of vascular endothelial growth factor for potential bone tissue engineering applications. PMID- 22781920 TI - Investigating the use of coupling agents to improve the interfacial properties between a resorbable phosphate glass and polylactic acid matrix. AB - Eight different chemicals were investigated as potential candidate coupling agents for phosphate glass fibre reinforced polylactic acid composites. Evidence of reaction of the coupling agents with phosphate glass and their effect on surface wettability and glass degradation were studied along with their principle role of improving the interface between glass reinforcement and polymer matrix. It was found that, with an optimal amount of coupling agent on the surface of the glass/polymer, interfacial shear strength improved by a factor of 5. Evidence of covalent bonding between agent and glass was found for three of the coupling agents investigated, namely: 3-aminopropyltriethoxysilane; etidronic acid and hexamethylene diisocyanate. These three coupling agents also improved the interfacial shear strength and increased the hydrophobicity of the glass surface. It is expected that this would provide an improvement in the macroscopic properties of full-scale composites fabricated from the same materials which may also help to retain these properties for the desired length of time by retarding the breakdown of the fibre/matrix interface within these composites. PMID- 22781921 TI - Positive and negative predictors for good outcome after decompressive surgery for Chiari malformation type 1 as scored on the Chicago Chiari Outcome Scale. AB - OBJECTIVE: Posterior fossa decompression (PFD) is commonly applied as treatment for Chiari malformation type 1 (CM1), an entity which is associated with a variety of presenting symptoms but little data correlating symptoms to surgical outcome. We applied the Chicago Chiari Outcome Scale (CCOS), a novel 16-point tool for evaluating outcome, to a consecutive series of CM1 patients to identify specific factors or symptoms that predispose to a better or worse surgical outcome. METHODS: A series of 167 CM1 patients who underwent initial PFD at our institution (consisting of suboccipital craniectomy, C1 laminectomy, subarachnoid exploration, and expansile autologous pericranial duraplasty) were reviewed. Pre-operative signs, symptoms, and characteristics were recorded, and odds ratios were calculated to identify significant pre-operative factors corresponding to a better or worse outcome on the CCOS. RESULTS: Sensory deficits and peripheral neuropathy correlated with a lower score on the CCOS. Younger age at the time of surgery and, strikingly, presence of syringomyelia both correlated with a higher CCOS score. DISCUSSION: Our results identify specific presenting factors that correlated with a better or worse outcome after CM1 decompression. These data also demonstrate that CCOS scoring allows for a rigorous comparison of outcome in different patient populations and between variable operative techniques. Application of CCOS scoring to a larger patient population undergoing a variety of operative CM1 treatments should allow for better-informed decisions regarding patient selection and treatment options for CM1. PMID- 22781922 TI - The entrance complex, transition state, and exit complex for the F + H2O -> HF + OH reaction. Definitive predictions. Comparison with popular density functional methods. AB - Following the H + H(2) and F + H(2) reactions, the fluorine atom - water system has the potential to become one of the best understood chemical reactions. Stationary points for the F + H(2)O potential energy surface have been located with the "Gold Standard" CCSD(T) method using the Dunning correlation consistent basis sets through quintuple zeta. The CCSD(T)/cc-pV5Z barrier height is prediced to be 2.5 kcal mol(-1), less than previous estimates of 4-7 kcal mol(-1). From higher level theoretical studies of the prototypical F + H(2) reaction, this barrier should be less than 0.5 kcal mol(-1) above the exact, nonrelativistic classical barrier height. 41 of the 49 DFT methods applied to F + H(2)O predict no barrier at all. The eight DFT methods that do predict a barrier show exothermicities that are somewhat too small. The CCSD(T)/cc-pV5Z entrance complex is bound by 3.4 kcal mol(-1) relative to separated F + H(2)O. The analogous exit complex is bound by 5.9 kcal mol(-1) relative to separated HF + OH. PMID- 22781923 TI - Isolation and primary culture of rat hepatic cells. AB - Primary hepatocyte culture is a valuable tool that has been extensively used in basic research of liver function, disease, pathophysiology, pharmacology and other related subjects. The method based on two-step collagenase perfusion for isolation of intact hepatocytes was first introduced by Berry and Friend in 1969 and, since then, has undergone many modifications. The most commonly used technique was described by Seglenin 1976. Essentially, hepatocytes are dissociated from anesthetized adult rats by a non-recirculating collagenase perfusion through the portal vein. The isolated cells are then filtered through a 100 MUm pore size mesh nylon filter, and cultured onto plates. After 4-hour culture, the medium is replaced with serum-containing or serum-free medium, e.g. HepatoZYME-SFM, for additional time to culture. These procedures require surgical and sterile culture steps that can be better demonstrated by video than by text. Here, we document the detailed steps for these procedures by both video and written protocol, which allow consistently in the generation of viable hepatocytes in large numbers. PMID- 22781924 TI - Differentiation of osteoblast and osteoclast precursors on pure and silicon substituted synthesized hydroxyapatites. AB - Calcium phosphate-based materials should show excellent bone-bonding and cell mediated resorption characteristics at the same time, in order to be employed for bone replacement. In this perspective, pure (HAp) and silicon-substituted hydroxyapatite (Si-HAp, 1.4% wt) porous cylinders were prepared starting from synthesized powders and polyethylene spheres used as porogens, and investigated as supports for osteoblast and osteoclast progenitor differentiation. A systematic and detailed biological characterization is reported, in terms of cell adhesion, viability, proliferation, differentiation and bioresorption, aimed at proposing a complete and reliable picture of bone cell in vitro behavior, comprehensive of both the osteogenesis and the bone resorption processes. In order to achieve this purpose, cytocompatibility, differentiation and gene expression by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) were carried out using parietal bone-derived pre-osteoblasts obtained from neonatal mice and the bioresorption capability was assessed by seeding human peripheral blood monocytes, as osteoclast precursors. It resulted that both pure and Si-substituted HAps were able to promote differentiation of precursor cells in mature osteoblasts and osteoclasts. In particular, the Si-HAps enhanced the pre-osteoblast proliferation and showed higher osteoclast-mediated bioresorption capability, as supported by the presence of larger and more numerous resorption lacunae, whereas HAps promoted a more robust cell differentiation in terms of both osteocalcin gene expression by qRT-PCR and cell morphological evaluation by SEM analysis. PMID- 22781925 TI - Building liquid crystals from the 5-fold symmetrical pillar[5]arene core. AB - Comparison of the liquid-crystalline properties of a pillar[5]arene core functionalized with 10 mesogenic cyanobiphenyl units with those of a corresponding model compound revealed the strong influence of the macrocyclic pillar[5]arene core on the mesomorphic properties. PMID- 22781926 TI - The potential application of functionally graded material for proximal femoral nail antirotation device. AB - Proximal femoral nail antirotation (PFNA) device is an intramedullary nail system designing for the treatment of trochanteric fractures. It is composed of a helical neck blade, a nail and a distal locking bolt. There were some reports of femoral shaft fractures even after the fractures were healed. The stress shielding effects of the PFNA device made of stiff titanium alloy on the bone remodeling behavior of the host femur and the uneven distribution of interface shear stress may contribute to this complication. Recently, a new class of composite called functionally graded material (FGM) was developed, that consisted a gradual pattern of material composition and/or microstructures, and was introduced in dental implant and cementless hip stem. Accordingly, in this paper, we hypothesized that FGM might be used as the material of the nail in PFNA device with the material composition of the nail gradually shifting from more stiff at the proximal side of the femur to more flexible 'iso-elastic' towards the distal side. This hypothesis can be evaluated from the long-term remodeling behavior of host femur and the stress distributions in the PFNA device and bone. PMID- 22781927 TI - IFAP syndrome with severe cutaneous, neurologic and skeletal manifestations due to a novel MBTPS2 mutation in a Polish patient. AB - BACKGROUND: Ichthyosis Follicularis, Atrichia and Photophobia (IFAP) syndrome is a rare genodermatosis due to mutations of the MBTPS2 gene. To date fewer than 40 cases have been described in the literature. OBJECTIVES: To present the first case of IFAP diagnosed in Poland due to a novel mutation of MBTPS2, and to review the relevant literature on this rare genodermatosis. MATERIALS & METHODS: A 16 year-old male presented with typical clinical features of IFAP, along with psoriasiform skin plaques, nail dystrophy, facial dysmorphy, mental retardation, severe skeletal abnormalities and chorea-like movements. DNA analysis was performed in the patient and his clinically unaffected mother, maternal grandmother and sisters. RESULTS: A novel missense mutation p.Cys334Tyr (c.1001G>A) was found in exon 8 of the MBTPS2 gene. This mutation was also found in his clinically unaffected mother and maternal grandmother, but not his healthy sisters. CONCLUSIONS: This patient with IFAP, the first described from Poland, is original by virtue of its extensive skeletal, cutaneous and neurologic manifestations and the novel missense mutation of the MBPTS2 gene. The identification of a novel mutation further expands the known MBPTS2 molecular repertoire and the spectrum of associated clinical findings. PMID- 22781928 TI - Regulation of XFGF8 gene expression through SRY (sex-determining region Y)-box 2 in developing Xenopus embryos. AB - Fibroblast growth factors (FGFs) function as mitogens and morphogens during vertebrate development. In the present study, to characterise the regulatory mechanism of FGF8 gene expression in developing Xenopus embryos the upstream region of the Xenopus FGF8 (XFGF8) gene was isolated. The upstream region of the XFGF8 gene contains two putative binding sites for the SRY (sex-determining region Y)-box 2 (SOX2) transcription factor. A reporter assay with serially deleted constructs revealed that the putative SOX2-binding motif may be a critical cis-element for XFGF8 gene activation in developing Xenopus embryos. Furthermore, Xenopus SOX2 (XSOX2) physically interacted with the SOX2-binding motif within the upstream region of the XFGF8 gene in vitro and in vivo. Depletion of endogenous XSOX2 resulted in loss of XFGF8 gene expression in midbrain-hindbrain junction, auditory placode, lens placode and forebrain in developing Xenopus embryos. Collectively, our results suggest that XSOX2 directly upregulates XFGF8 gene expression in the early embryonic development of Xenopus. PMID- 22781929 TI - Transcriptional response of the bovine endometrium and embryo to endometrial polymorphonuclear neutrophil infiltration as an indicator of subclinical inflammation of the uterine environment. AB - The aim of the present study was to analyse the effect of subclinical endometritis on endometrial and embryonic gene expression. A total of 49 cows at either Day 0 or Day 7 of the oestrous cycle (62-83 days post partum) following superovulation were classified as having subclinical endometritis (SE-0, SE-7) or a healthy endometrium (HE-0, HE-7) on the basis of endometrial cytological evaluation. Endometrial samples and associated embryos were subjected to global transcriptome analysis using the Bovine GeneChip (Affymetrix, Santa Clara, CA, USA) and aberrant transcript profiles were observed in SE-0 and SE-7 cows. At Day 0, 10 transcripts were found to be differentially expressed in endometrial samples. Specifically, the PDZK1, PXDN, DDHD2, GPLD1 and SULT1B1 genes were downregulated, whereas the PKIB, LOC534256, BT29392, LYZ and S100A14 genes were upregulated in SE-0 cows. Similarly, 11 transcripts were found to be differentially regulated on Day 7. Of these, GNPTG, BOLA-DQA5, CHD2, LOC541226, VCAM1 and ARHGEF2 were found to be downregulated, whereas PSTPIP2, BT236441 and MGC166084 were upregulated in SE-7 cows. Accordingly, endometrial health status affected the number of flushed, transferable embryos. In all, 20 genes were differentially regulated in blastocysts derived from HE-7 and SE-7 cows. Of these, GZMK, TCEAL4, MYL7, ADD3 and THEM50B were upregulated, whereas NUDCD2, MYO1E, BZW1, EHD4 and GZMB were downregulated. In conclusion, endometrial polymorphonuclear neutrophil infiltration as an indicator of subclinical endometritis is associated with changes in endometrial gene expression patterns, including genes involved in cell adhesion and immune modulation. Consequently, subclinical endometritis affects gene expression in embryos, including the expression of genes related to membrane stability, the cell cycle and apoptosis. PMID- 22781930 TI - Melatonin effects on Fundulus heteroclitus reproduction. AB - This study aimed to investigate the effects of two different doses (100nM (M1) and 1uM (M2)) of exogenous melatonin on the reproductive capacity of Fundulus heteroclitus. Eight days of melatonin exposure significantly increased the fecundity and embryo survival of F. heteroclitus only in the M2 group compared with the control; the hatching rate was unaffected. Moreover, increases in the local expression of the melatonin receptor (mtnr) gene during follicle maturation were found; however, there were no differences between the experimental groups. Furthermore, in vitro melatonin-treated follicles showed a significantly higher germinal vesicle break down percentage compared with the control, while SDS-PAGE showed no difference in the electrophoretic pattern of the major yolk proteins. Nevertheless, densitometry revealed a greater intensity of the 118-, 95- and 40 kDa components in groups treated with melatonin. Finally, Fourier transform infrared microspectroscopy was applied to classify the different stages of oocyte development (Stages I-II, III and IV) on the basis of their macromolecular composition. The effects induced by melatonin on oogenesis were investigated by comparing vibrational spectra of females exposed to melatonin with those of controls. Changes to the Amide I band, corresponding to an increase in beta structure, were found in oocytes of females exposed to the highest melatonin dose. These results highlight the positive role of melatonin, which is able to enhance the reproductive capacity of F. heteroclitus. Further studies are in progress to better explain the molecular mechanisms by which melatonin treatment affects reproduction in this marine species. PMID- 22781931 TI - Parental diet-induced obesity leads to retarded early mouse embryo development and altered carbohydrate utilisation by the blastocyst. AB - Maternal obesity results in reproductive complications, whereas the impact of paternal obesity is unclear. In the present study, the effects of parental obesity on preimplantation embryo cell cycle length and carbohydrate utilisation were investigated. Maternal and paternal obesity were assessed independently by deriving zygotes from normal or obese C57BL/6 female mice mated with normal Swiss male mice (maternal obesity), or from normal Swiss female mice mated with normal or obese C57BL/6 male mice (paternal obesity). Zygotes were cultured in vitro and development was then assessed by time-lapse microscopy and metabolism determined using ultramicrofluorescence. Maternal obesity was associated with a significant delay in precompaction cell cycle kinetics from the 1-cell stage. A significant increase in glucose consumption by embryos from obese compared with normal females occurred after compaction, although glycolysis remained unchanged. Similarly, paternal obesity led to significant delays in cell cycle progression during preimplantation embryo development. However, this developmental delay was observed from the second cleavage stage onwards, following embryonic genome activation. Blastocysts from obese males showed disproportionate changes in carbohydrate metabolism, with significantly increased glycolysis. Overall, metabolic changes were not inhibitory to blastocyst formation; however, blastocyst cell numbers were significantly lower when either parent was obese. These data suggest that both maternal and paternal obesity significantly impacts preimplantation embryo physiology. PMID- 22781932 TI - IVMBIX-01294, an inhibitor of the histone methyltransferase EHMT2, disrupts histone H3 lysine 9 (H3K9) dimethylation in the cleavage-stage porcine embryo. AB - Global patterns of histone methylation are remodelled during cleavage development. Of the five histone methyltransferases known to mediate methylation of the lysine 9 residue of histone H3 (H3K9), euchromatic histone-lysine N methyltransferase 2 (EHMT2; also known as G9a) has been shown to be a primary mediator of H3K9 dimethylation; BIX-01294 has been shown to be a specific inhibitor of EHMT2. The objective of the present study was to determine the effect of BIX-01294 treatment on global H3K9 dimethylation in porcine embryos. We hypothesised that inhibition of EHMT2 by BIX-01294 would result in reduced levels of H3K9 dimethylation and compromised embryo development. Our results showed that incubation in 5uM BIX-01294 markedly reduced global levels of H3K9 dimethylation at the pronuclear, 2-cell and 4-cell stages of development and resulted in developmental arrest before blastocyst formation. Although transient exposure of embryos to BIX-01294 did not alter in vitro development, embryos transiently exposed to BIX-01294 did not establish pregnancy. These data demonstrate that BIX 01294 is a potent inhibitor of H3K9 dimethylation and that transient alterations in global histone modifications can have profound effects on embryo developmental potential. PMID- 22781933 TI - Seasonal variation in the ovarian function of sows. AB - The modern domestic sow exhibits a period of impaired reproductive performance known as seasonal infertility during the late summer and early autumn months. A reduction in farrowing rate due to pregnancy loss is the most economically significant manifestation of this phenomenon. Presently, little is known of the aetiology of seasonal pregnancy loss in the pig. Recent findings represent a major advancement in the understanding of sow reproductive physiology and implicate poor oocyte developmental competence as a contributing factor to pregnancy loss during the seasonal infertility period. It has also been demonstrated that ovarian activity is depressed during the seasonal infertility period. The reduction in oocyte quality is associated with decreased levels of progesterone in follicular fluid during final oocyte maturation in vivo. The recent identification of sow-specific risk factors, such as parity for late pregnancy loss, should improve breeding herd efficiency by allowing producers to tailor management interventions and/or culling protocols that target animals identified as having a greater risk of late pregnancy loss during the seasonal infertility period. PMID- 22781934 TI - Uterine distension differentially affects remodelling and distensibility of the uterine vasculature in non-pregnant rats. AB - During pregnancy the mammalian uterine circulation undergoes significant expansive remodelling necessary for normal pregnancy outcome. The underlying mechanisms are poorly defined. The goal of this study was to test the hypothesis that myometrial stretch actively stimulates uterine vascular remodelling by developing a new surgical approach to induce unilateral uterine distension in non pregnant rats. Three weeks after surgery, which consisted of an infusion of medical-grade silicone into the uterine lumen, main and mesometrial uterine artery and vein length, diameter and distensibility were recorded. Radial artery diameter, distensibility and vascular smooth muscle mitotic rate (Ki67 staining) were also measured. Unilateral uterine distension resulted in significant increases in the length of main uterine artery and vein and mesometrial segments but had no effect on vessel diameter or distensibility. In contrast, there were significant increases in the diameter of the radial arteries associated with the distended uterus. These changes were accompanied by reduced arterial distensibility and increased vascular muscle hyperplasia. In summary, this is the first report to show that myometrial stretch is a sufficient stimulus to induce significant remodelling of uterine vessels in non-pregnant rats. Moreover, the results indicate differential regulation of these growth processes as a function of vessel size and type. PMID- 22781935 TI - Cortical reaction as an egg quality indicator in artificial reproduction of pikeperch, Sander lucioperca. AB - The aim of this study was to investigate the process of the cortical reaction in eggs of pikeperch, Sander lucioperca (L.), as well as the application of microscopic assessment of this process in egg quality evaluation. The analysis was carried out with eggs obtained from 10 females by artificial reproduction, in which hormonal stimulation with hCG was applied. Subsequently, each sample of eggs (separately from each female fish) was analysed. The analysis included observation of the cortical reaction and the process of egg swelling, and determination of the effect of temperature (12, 14 and 16 degrees C) and the presence of spermatozoa on the cortical reaction. The results indicate that the cortical reaction in pikeperch eggs is quite violent, resulting in visible deformation of eggs between 3 and 5 min after activation. No effect of temperature or the presence of spermatozoa on the cortical reaction was observed. A strong correlation was recorded for the percentage of egg deformations observed and embryo survival rate. The described method of determination of pikeperch egg quality (based on egg deformation rate between 3 and 5 min after activation) may be highly useful, both in scientific research (where high-quality eggs are required) and in hatchery practice. PMID- 22781936 TI - Expression of angiogenic factors in placenta of stressed rats. AB - The aim of the present study was to analyse the influence of stress on pregnant rats, particularly in terms of maternal, placental and fetal weight, placental morphology and placental gene expression of the angiogenic factors Vegfa and Pgf and their receptors. The parameters were evaluated on gestation Day 20. Maternal, fetal and placental weights were statistically lower in stressed animals than controls, suggesting abnormalities in gestational physiology. Morphologically the placentas of rats subjected to stress were reduced in size and weight, with few glycogen cells and a significant increase in the number of apoptotic cells. Stress caused an increase in placental gene expression of Vegfa (P<0.05) and a reduction in Pgf, Flt1 and Kdr expression (P<0.05). It has been suggested that increased VEGF is associated with vasodilatation and hypotension, but in this model persistent hypertension was present. This study suggests that the limited hypotensive Vegfa response to stress-induced hypertension could result from reduced expression of Flt1/Kdr disrupting specific VEGF pathways. These findings may elucidate one of the multiple possible factors underlying how stress modulates placental physiology, and could aid the understanding of stress-induced gestational disorders. PMID- 22781937 TI - A rodent model of low- to moderate-dose ethanol consumption during pregnancy: patterns of ethanol consumption and effects on fetal and offspring growth. AB - It is unknown whether low to moderate maternal alcohol consumption adversely affects postnatal health. The aim of the present study was to develop a rodent model of low-moderate-dose prenatal ethanol (EtOH) exposure. Sprague-Dawley rats were fed a liquid diet with or without 6% v/v EtOH throughout gestation and the pattern of dietary consumption determined. Fetal bodyweights and hepatic alcohol metabolising gene expression were measured on embryonic Day (E) 20 and offspring growth studied until 1 year. At E8 the plasma EtOH concentration was 0.03%. There was little difference in dietary consumption between the two treatment groups. At E20, EtOH-exposed fetuses were significantly lighter than controls and had significantly decreased ADH4 and increased CYP2E1 gene expression. Offspring killed on postnatal Day (PN) 30 did not exhibit any growth deficits. Longitudinal repeated measures of offspring growth demonstrated slower growth in males from EtOH-fed dams between 7 and 12 months of age; a cohort of male pups killed at 8 months of age had a reduced crown-rump length and kidney weight. In conclusion, a liquid diet of 6% v/v EtOH fed to pregnant dams throughout gestation caused a 3 8% reduction in fetal growth and brain sparing, with growth differences observed in male offspring later in life. This model will be useful for future studies on the effects of low-moderate EtOH on the developmental origins of health and disease. PMID- 22781938 TI - Effect of tubal explants and their secretions on bovine spermatozoa: modulation of ROS production and DNA damage. AB - Although low levels of reactive oxygen species (ROS) play a physiological role in maintaining sperm function, an increase in ROS generation above these levels may result in the induction of sperm membrane and DNA damage. The main objective of this study was to determine whether bovine oviducal explants (TU) and their conditioned media (CM) have a modulatory effect on the production of ROS, and consequently, on sperm DNA integrity. Thawed sperm were exposed to bovine TU and to CM obtained from the ampullar and isthmal regions after 4 and 12h, and DNA damage and intracellular ROS production was assessed by TUNEL and DHE and SYTOX Green, respectively. Co-incubation of spermatozoa with oviducal explants from the ampullar region (TUa) for 4h resulted in a statistically significant increase in the percentage of spermatozoa with DNA damage compared with controls (P=0.0106), and this increase was positively correlated with ROS levels. Conversely, although the incubation of spermatozoa with explants and conditioned media from the isthmal region (TUi and CMi, respectively) for 12h resulted in an increase of spermatozoa with DNA damage compared with controls (P<0.0001), this increase was not correlated with ROS levels. In conclusion, significant oxidative stress may take place in the oviduct, particularly during short-term incubation, and this may be related to changes in the antioxidant factors present in the oviducal cells and secretions. A redox imbalance in pro-oxidants and antioxidants in the oviduct may lead to oxidative stress and sperm DNA damage. PMID- 22781939 TI - Development of spermatogenesis in captive-bred Spix's yellow-toothed cavy (Galea spixii). AB - The aim of this study was to evaluate the phases of sexual development and spermatogenesis of Spix's yellow-toothed cavy (Galea spixii) based on analyses of the structural components of the testes. The testes of animals from 0 to 150 days of age were collected by orchiectomy, weighed, and processed for analysis by light microscopy. At 45 days of age, spermatozoa were seen in the tubular lumen. Spermatogenesis was not established in animals from 45 to 150 days of age. The stages of sexual development may be classified into the following phases: from birth to the age of 15 days (immature); 30 days of age (prepubertal); 45-105 days of age (pubertal); and 120 and 150 days of age (postpubertal). This is the first study to address the male reproductive biology of Spix's yellow-toothed cavy. PMID- 22781940 TI - Undernutrition during early follicle development has irreversible effects on ovulation rate and embryos. AB - This study assessed carry-over effects of energy level during the early antral phase and subsequent follicular phase on follicle recruitment and ovulation rate. Gilts (n=45) were fed a standard diet to a low (L, ~1.2kg day(-1)) or high (H, ~2.7kg day(-1)) level during the early antral (luteal) phase, and subsequently fed a H or L feed level during the follicular phase, resulting in four treatment groups (HH, HL, LH and LL). Follicle size at the end of the luteal phase was greater for gilts fed a high feed level previously (3.3vs3.0mm; P<0.05). During the follicular phase, high feeding increased follicle size at Day 5 (6.9vs6.2mm; P<0.005) and plasma oestradiol concentration (P<0.05). Nevertheless, a low feed level during the luteal phase reduced ovulation rate (14.4vs13.2; P<0.05) and embryo number (12.6vs10.5; P<0.05), and this was not counteracted by feed level during the follicular phase. Plasma progesterone concentration after ovulation was lower for LL gilts than for other treatments (P<0.05). These results indicate that undernutrition during early antral follicle development may have a residual effect on follicle recruitment and quality. PMID- 22781942 TI - [Guidance on management of common cold]. PMID- 22781941 TI - Surface acoustic wave (SAW) acoustophoresis: now and beyond. AB - On-chip manipulation of micro-objects has long been sought to facilitate fundamental biological studies and point-of-care diagnostic systems. In recent years, research on surface acoustic wave (SAW) based micro-object manipulation (i.e., SAW acoustophoresis) has gained significant momentum due to its many advantages, such as non-invasiveness, versatility, simple fabrication, easy operation, and convenient integration with other on-chip units. SAW acoustophoresis is especially useful for lab-on-a-chip applications where a compact and non-invasive biomanipulation technique is highly desired. In this Focus article, we discuss recent advancements in SAW acoustophoresis and provide some perspectives on the future development of this dynamic field. PMID- 22781943 TI - [A survey of knowledge on common cold in outpatient clinics]. AB - OBJECTIVE: To investigate outpatients' cognition towards common cold and their habituated medication so as to provide evidence for future public healthcare education. METHODS: Patients who attended hospital for diagnosis and treatment of common cold at least within past three months were asked to fill a questionnaire independently so as to learn their cognition towards common cold and medication habit. RESULTS: Among the patients underwent survey, 52.21% had incorrect knowledge about common cold; 12.99% didn't know about the hazards of common cold; 34.80% couldn't distinguish common cold from influenza; 30.07% considered common cold couldn't get relief without treatment; 68.24% didn't know about the proper effects of influenza vaccination; 61.14% often took oral medicine even intravenous injection when they caught a common cold; 59.77% often took medication from drugstore without prescription by doctor, and a few asked doctors to prescribe medicine on their request; 19.42% didn't know about the side effects of drug for cold treatment; and 19.72% didn't know about the active ingredients of drug for cold treatment. There were significant differences in the common cold cognition among population of different ages and education background. The older or the higher education status patients had a better cognition (P < 0.01). CONCLUSION: There exist a certain degree of wrong cognition towards common cold among patients of different literacy degree and different age. Public health education on common cold need to be further strengthened. PMID- 22781944 TI - [A survey of knowledge on common cold and its treatment situation among physicians from various levels of hospitals in mainland China]. AB - OBJECTIVE: To investigate the cognition of the common cold and current situation of the treatment among physicians from various levels of hospitals in Chinese mainland, so as to provide evidence for future continuing medical education and rational medication. METHODS: A questionnaire designed for this survey was used to learn about the general information, cognitive degree of the common cold and prescription habits of physician who prescribed for cold within last three months, from various levels hospitals. RESULTS: A total of 1001 physicians were interviewed. Among them, 749 physicians chose right options that the cold was the common cold and the influenza with 79.84% in resident physicians and 56.76% in chief physicians. A total of 745 physicians chose options that the course of common cold will be lasting 4 to 7 days; 895 physicians chose options that old people are the most susceptible for complication; 669 physicians thought the common cold was the most common infection in winter; 841 physicians used clinical methods to diagnose the common cold; 736 physicians thought although the cold was a kind of self-limited disease and symptomatic treatment could alleviate symptoms and improve life quality, patients should see doctor in time if it turns to severer; and 745 physicians held the opinion that treatment of the common cold should focus on relieving symptoms first. In addition, 61.60% physicians had made prescription based on clinical symptoms; 505 (54.24%) of them thought compound drugs were priority in treating the common cold. However, there were still 43 physicians prescribed antibiotics for common cold. CONCLUSIONS: There is misunderstanding and discrepancy in cognition towards common cold and treatment among physicians from various levels of hospitals in mainland China. Physicians should standardize diagnosis and treatment for the common cold according to the domestic and foreign guidelines. PMID- 22781945 TI - [The expression of interferon associated genes mRNA in patients with pulmonary embolism]. AB - OBJECTIVE: To investigate the gene expression difference of IFN and their receptors in peripheral blood mononuclear cells (PBMC) of pulmonary embolism (PE) patients. METHODS: Twenty cases of PE patients and twenty sex and age matched controls were recruited into the study. Human cDNA microarray analysis was used to detect the gene expression difference of IFN associated genes between the two groups, and random variance model corrected t test was used to analyze the statistical data. RESULTS: In comparison with the control group, mRNA expression of type I IFN, including IFNalpha(5) mRNA, IFNalpha(6) mRNA, IFNalpha(8) mRNA, IFNalpha(14) mRNA, IFNkappa mRNA, IFNomega(1) mRNA, IFNepsilon(1) mRNA in PBMC of PE patients were down-regulated (P < 0.05). There was no significant difference in gene expression of type I IFN receptors IFNalphaR(1) and IFNalphaR(2) between the PE and control groups (P > 0.05). In comparison with the control group, mRNA expression of IFNgamma gene was down-regulated (P < 0.05). The mRNA expression of IFNgammaR(1) and IFNgammaR(2) genes were upregulated compared with the control (P > 0.05). CONCLUSION: mRNA expression of type I and type II IFN in PE are significantly down-regulated, but not the IFN receptors. Reduced immune function may play an important role in the PE patients who are susceptible to virus, intracellular bacteria and parasites. PMID- 22781946 TI - [The epidemiology of out-of-hospital deaths due to acute coronary events in young Beijing adults]. AB - OBJECTIVES: To explore the characteristics of status and different populations of prehospital death associated with acute coronary events among young adults in Beijing. METHODS: Data of acute coronary events of hospitalization or death were obtained from the Hospital Discharge Information System from Beijing Public Health Information Center and Death Register System from Beijing Center for Disease Control in Beijing. The total case fatality rate of acute coronary events and proportion of prehospital coronary heart disease (CHD) death were compared upon gender, area, occupation and marital status among people aged between 25 - 45 years old. RESULTS: A total of 3489 cases were identified during 2007 to 2009 with acute coronary events (male: 3183, female: 306), with a mean age of (40.5 +/ 4.3) years old. The 3-years' overall mortality was 26.0%, with female's higher than male's (51.0% vs 23.6%, P < 0.05); and it was higher in rural area than in urban areas (28.9% vs 22.9%, P < 0.05). Ninety-five percent of death due to acute coronary events occurred prehospital, with the proportion of 95.2% in male and 94.2% in female. Among the people with different occupations, self-employed people had the highest rate of prehospital death. Majority of prehospital deaths (64.8%) occurred at home. CONCLUSION: More than 90% of deaths caused by acute coronary events among young adults aged between 25-45 years old occurred before been admitted into hospital, and the site of prehospital deaths was mainly at home. PMID- 22781947 TI - [The efficacy and safety of bortezomib-based induction regimen before autologous hematopoietic stem cell transplantation in patients with multiple myeloma]. AB - OBJECTIVE: To investigate the efficacy and safety of bortezomib-based induction regimen followed by autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM). METHODS: A retrospective analysis was performed upon clinical data of 62 MM patients who received bortezomib-based induction regimen followed by ASCT from June 2006 to June 2011. All patients were followed up to September 30, 2011. RESULTS: Overall response rate [complete remission (CR) + near complete remission (nCR) + partial remission (PR)], >= nCR rate (CR/nCR) and CR rate of post-induction with bortezomib-based regimen were 88.7%, 66.1% and 24.2%, respectively. After ASCT, CR rate and CR/nCR rate were increased to 50.0% and 82.3%, respectively, with significant differences (P = 0.003 and P = 0.032). The median time of neutrophil and platelet engraftment was 12.0 (9 - 43) days and 13.5 (0 - 120) days, respectively. Significances were found in neutrophil and platelet engraftment between MM patients with and without prior exposure to alkylating agents. Furthermore, engraftment of neutrophil and platelet in patients receiving peripheral blood stem cell transplantation were faster than those receiving bone marrow transplantation. No unexpected side effects occurred. The median time of follow-up was 26.5 (7-61) months. The median overall survival (OS) was not reached and the median progression-free survival (PFS) was 30 months. There were significant differences in OS and PFS between patients obtaining CR/nCR and those with <= PR before ASCT. CONCLUSIONS: Bortezomib-based induction regimen can improve the efficacy of ASCT in MM patients. The side effects are tolerant. Higher response quality before ASCT can translate to high rates of OS and PFS following high-dose therapy and stem cell transplantation. PMID- 22781948 TI - [The value of esophageal intrapapillary capillary loop visualized by magnifying narrow-band imaging endoscopy in diagnosing esophageal mucosal pathology]. AB - OBJECTIVE: To investigate the diagnostic potential of magnifying narrow-band imaging endoscopy (NBI-ME) for different intrapapillary capillary loop (IPCL) for the diagnosis of esophageal lesion. METHODS: Patients with abnormal esophageal mucosa found by white light gastroscopy in digestive endoscopy center, Chinese PLA General Hospital during the period of November 2009 to November 2010 were enrolled in this study. IPCL was observed and divided into different types by NBI ME. Histopathology of biopsy or endoscopic submucosal dissection (ESD) specimens was evaluated and used as the gold standard to evaluate the diagnostic value of NBI-ME for IPCL. RESULTS: A total of 146 lesions from 145 subjects with esophageal mucosa abnormal were collected. Among them, 88 were pathology-proven inflammation, 5 were pathology-proven esophageal cancers, 20 were pathology proven low intraepithelial neoplasia (LIN) and 33 were pathology-proven high intraepithelial neoplasia (HIN) detected with NBI-ME. By a per-lesion analysis, the accuracy of inflammation and cancer were 100% (88/88) and 7/7. For the sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio of LIN and HIN were 7/10, 69.8% (30/43), 69.8% (37/53), 35.0% (7/20), 90.9% (30/33), 12.5% (70/559), 2.3% (30/1290) and 87.1% (27/31), 72.7% (16/22), 81.1% (43/53), 81.8% (27/33), 80.0% (16/20), 634.1% (837/132) and 35.2% (124/352), respectively. CONCLUSIONS: NBI-ME can classify the different esophageal IPCL. Higher diagnostic accuracy of IPCL indicates the feasibility of NBI-ME for the efficacious diagnosis of esophageal inflammation and cancer. There is the higher diagnostic accuracy of HIN than LIN. PMID- 22781949 TI - [The clinical characteristic of 43 cases of neuroendocrine tumors with liver metastases]. AB - OBJECTIVE: To analyze the clinical characteristics of liver metastases of neuroendocrine tumors (NET) and its treatment outcome, so as to further cognition of NET. METHODS: The clinical data of patients with liver metastases of NET diagnosed by Peking Union Medical College Hospital during January 1996 to July 2010 were analyzed retrospectively. RESULTS: The ratio of male to female was 1:1.15 (20:23). The median age at onset of the patients with liver metastases of NET was 47.5 (26 - 70) years. The median duration from onset to diagnosis was 4 (0 - 120) months. The liver metastases were the first manifestation in 69.8% (30/43) cases. The detection rate of primary lesions with routine abdominal imaging (B-type ultrasonography, CT, MRI) was 65.1% (28/43), while increased to 90.7% (39/43) when combined the following one or more special examinations including somatostatin receptor scintigraphy (SRS), PET-CT, endoscopic ultrasound (EUS) (P = 0.004). The definite diagnosis methods mainly depended on surgical specimens (69.8%, 30/43). The ratio of nonfunctional to functional NET with liver metastases was 1.87:1 (28:15). The primary tumors were most commonly located in pancreas [39.3% (11/28) and 73.3% (11/15)], followed by stomach [21.4% (6/28) and 13.3% (2/15)]. Totally 88.4% (38/43) patients received operation, and 9.3% (4/43) patients had reoperation due to missed diagnosis of the primary tumors on earlier operation. Non-surgical treatments included octreotide acetate long-acting release, interventional therapy, chemotherapy and radiotherapy, which were difficult to be evaluated due to less follow-up cases. CONCLUSIONS: Liver metastases of NET are common and even the first manifestation symptom. Primary NET with liver metastases is the most commonly nonfunctional and located in digestive system. The detection rates of primary lesions are increased by special examinations including SRS, PET-CT and EUS. Surgical specimens are helpful to the final diagnosis, but it is necessary to improve the preoperative diagnostic rate of primary tumors to avoid repeat surgeries. PMID- 22781950 TI - [Differences of blood plasma renin activity, angiotensin II and aldosterone levels in essential or secondary hypertension]. AB - OBJECTIVE: To study on the difference of plasma renin activity (PRA), angiotensin II (Ang II), and aldosterone levels in patients with essential hypertension (EH) or primary aldosteronism (PA) or pheochromocytoma (PHEO), and to analyze the sensitivity and specificity on the diagnosis of PA among patients with hypertension with aldosterone/PRA ratio (ARR). METHODS: The plasma aldosterone, Ang II and PRA concentrations in supine and upright positions were measured by radioimmunoassay from 413 patients including idiopathic hyperaldosteronism (IHA, n = 111), aldosterone-producing adenoma (APA, n = 118), PHEO (n = 98) and EH (n = 86). ARR was calculated. RESULTS: Plasma aldosterone concentrations in both of supine and upright positions in PHEO group [374 (294, 465) pmol/L and 629 (449, 997) pmol/L] and PA group [471 (346, 632) pmol/L and 673 (499, 825) pmol/L] were higher than those in EH group [277 (224, 332) pmol/L and 427 (341, 501) pmol/L] (P < 0.01). They were also higher in APA group [576 (416, 731) pmol/L and 726 (554, 906) pmol/L] than those in IHA group [399 (313, 504) pmol/L and 609 (485, 776) pmol/L] (P < 0.01). Ang II levels in both positions were lower in PA group [43.2 (26.4, 74.4) ng/L and 60.1 (38.5, 103.6) ng/L] than in EH group [56.7 (43.3, 78.9) ng/L and 84.3 (61.3, 108.4) ng/L] or PHEO group [54.3 (29.9, 101.5) ng/L and 102.8 (49.9, 167.0) ng/L] (all P values < 0.01), and there was no difference between IHA and APA group (P > 0.05). The PRA level in both positions of each group were PHEO group [0.3 (0.2, 1.0) ug . L(-1) . h(-1) and 1.4 (0.6, 3.4) ug . L(-1) . h(-1)] > EH group [0.2 (0.1, 0.4) ug . L(-1) . h(-1) and 0.6 (0.4, 1.0) ug . L(-1) . h(-1)] (P < 0.01) > PA group [0.1 (0.1, 0.1) ug . L(-1) . h(-1) and 0.2 (0.1, 0.3) ug . L(-1) . h(-1)] (P < 0.01), and APA group [0.1 (0.1, 0.1) ug . L(-1) . h(-1) and 0.1 (0.1, 0.3) ug . L(-1) . h(-1)] < IHA group [0.1 (0.1, 0.2) ug . L(-1) . h(-1) and 0.2 (0.1, 0.3) ug . L(-1) . h(-1)] (supine P < 0.01; upright P < 0.05). APA was divided into 2 types with renin-Ang II responsive APA (n = 26) and unresponsive APA (n = 92). The plasma aldosterone concentration was lower in supine position but higher in upright position in renin-Ang II-responsive APA than in unresponsive APA patients. ARR in upright was higher in PA group (P < 0.01) but lower in PHEO group (P < 0.05) compared with EH. ARR was higher in APA than in IHA (P < 0.01). The sensitivity and specificity of ARR as 40 (aldosterone unit: ng/dl; PRA unit: ug . L(-1) . h(-1); its value should multiply 27.7 when transferred to pmol/L, simili) were 93% and 76%, respectively. CONCLUSION: The levels of PRA, Ang II and aldosterone from patients with EH, PA and PHEO are significant different. ARR as 40 in upright position could be used for PA screening cutoff point. PMID- 22781951 TI - [Different prevalence of impaired glucose tolerance between hyperinsulinemic and normoinsulinemic subjects]. AB - OBJECTIVE: To study the impact of different insulin levels on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM), through analysis of different glycometabolism condition among quinquagenarian population. METHODS: Subjects enrolled were Beijing habitants who received annual physical examination [including oral glucose tolerance test (OGTT)] in the Chinese PLA General Hospital from 2005 - 2007. According to the OGTT results, the subjects were divided into three groups, including normal glucose tolerance-non hyperinsulinemia group (NGT-NHIns), IGT-hyperinsulinemia group (IGT-HIns) and IGT non-hyperinsulinemia group (IGT-NHINS). The prognosis between the year 2009 and 2010 of the three groups was observed. Hyperinsulinemia was diagnosed with fasting serum insulin >= 15 mU/L and/or 2-hour serum insulin >= 80 mU/L after glucose loading. RESULTS: The rate of case number of conversion to T2DM in IGT NHIns group (42/133) was higher than that in IGT-HIns group (24/154) or NGT-NHIns group (12/126). The HOMA insulin resistance index (HOMA-IR) of individuals with IGT-NHIns was lower than that of IGT-HIns [0.96 (0.40, 3.53) vs 2.04 (0.59, 23.20), P < 0.05], while whole body insulin sensitivity index (WBISI) was higher than that of IGT-HIns [7.48 (3.20, 31.35) vs 3.28 (0.86, 7.67), P < 0.05]. Modified beta-cell function index (MBCI) and insulin secretion index (ISI) in IGT NHIns was poorer than that of IGT-HIns respectively [2.57 (0.58, 10.98) vs 5.17 (1.04, 65.09); 7.66 (0.99, 28.40) vs 17.56 (4.18, 96.46), all P values < 0.01]. CONCLUSIONS: The risk of IGT-NHIns progressing into T2DM is higher than that of IGT-HIns. For the prevention of T2DM, individuals with IGT-NHIns should be paid more attention than keeping an eye on IGT-HIns patients. Early control of risk factors could protect beta cell function and prevent the progression to T2DM. PMID- 22781952 TI - [The diagnostic value of musculoskeletal ultrasound in gouty arthritis]. AB - OBJECTIVE: To observe the characteristic features of musculoskeletal ultrasound (MSUS) in gouty arthritis (GA) and to assess its value in GA diagnosis. METHODS: Patients with GA and non-GA who underwent MSUS examination in Chinese PLA General Hospital were enrolled in this study. The synovitis, tenosynovitis, soft tissue swelling, bone erosion, bursitis and ossification were measured by grey-scale ultrasound, and the synovial vascularity was measured by power Doppler ultrasound to evaluate the degree of inflammation. RESULTS: The ultrasound images of GA were intended to have specific features like tophus, hyperechoic deposition on the surface of the articular hyaline cartilage (double contour sign), hyperechoic deposition in the synovium appearing as bright stippled foci, and bright strap in tendons with a significant difference when compared with non-GA group (P < 0.05). The percentage of tenosynovitis and bone erosion in non-GA group was higher than that in the GA group with a significant difference (P < 0.05). Tophus, double contour sign, bright stippled foci or bright stippled foci in tendons together suggested gout with a specificity of 92.4% and a sensitivity of 60.3%, the AUC of ROC was 0.764 (P < 0.05). CONCLUSION: Tophus, double contour sign, bright foci and bright strap detected by MSUS are of diagnostic value on GA and MSUS may be a promising tool in diagnosing GA. PMID- 22781953 TI - [The relation between plasma homocysteine level and amyotrophic lateral sclerosis]. AB - OBJECTIVE: To investigate the relationship between plasma level of homocysteine (Hcy) and amyotrophic lateral sclerosis (ALS). METHODS: The differences of Hcy, Vitamin B(12), and folate levels between 150 outpatients with ALS and 137 age and sex matched controls were compared in a cross-sectional study. RESULTS: Compared with the healthy controls, patients with ALS had a higher plasma Hcy level [(18.47 +/- 13.09) umol/L vs (11.91 +/- 5.37) umol/L, P < 0.001] and a lower folate level [(8.39 +/- 4.45) ng/ml vs (10.38 +/- 5.01) ng/ml, P < 0.001]. In a logistic regression model using ALS as a dependent variable, plasma level of Hcy was significantly associated with ALS. A trend for higher Hcy levels in patients with shorter interval from symptom onset to diagnosis (ODI) was also found [Hcy levels (20.73 +/- 15.79) umol/L with ODI < 19 months vs (16.41 +/- 9.73) umol/L with ODI >= 19 months, P = 0.035]. CONCLUSIONS: Plasma Hcy level is significantly increased in patients with ALS. The individuals with shorter time to diagnosis present higher Hcy level, suggesting that it may associate with the progression pace of ALS. PMID- 22781954 TI - Diversity and evolution of conotoxins in Conus virgo, Conus eburneus, Conus imperialis and Conus marmoreus from the South China Sea. AB - The venom peptides of cone snails are encoded by a large gene family, and can selectively bind to voltage-gated ion channels (Na+, K+ and Ca2+ channels) and to membrane receptors (nAChR, 5-HT3R, NMDAR). To identify novel conotoxin genes and analyze the evolution of typical conotoxin superfamily genes from different Conus species, we have constructed cDNA libraries derived from the venom ducts of Conus virgo, Conus eburneus, Conus imperialis and Conus marmoreus, which were collected from the South China Sea. 1312 transcripts from four Conus venom duct cDNA libraries were analyzed and 38.7-49.6% of the transcripts encoded conotoxin sequences. In addition to known conotoxins, 34 novel conotoxins have been identified and can be classified into eleven superfamilies, some of which showed unique patterns of cysteines or different signal peptide sequences. The evolutionary trees of T- and A-superfamily conotoxins were analyzed. Likelihood approaches revealed that T-superfamily conotoxins from the four Conus species undergo positive selection, mostly located in the mature toxin region. These findings contribute to a better understanding of the diversity and evolution of conotoxins from the South China Sea, and some novel conotoxins are valuable for further functional investigations. PMID- 22781955 TI - From static electric images to electric flow: towards dynamic perceptual cues in active electroreception. AB - Active electroreception is an ancestral trait found in many aquatic vertebrates and has evolved independently in two teleost lineages, the Gymnotiformes and the Mormyriformes. Unique to these so-called weakly electric fish is their ability to actively generate electrical currents in the water and sense the electrical properties of the environment. How natural behavior contributes to this sensory system has been of interest to neuroethologists since the pioneering works of Lissmann. Here we report on a mutual modeling and experimental study of the stimuli available during active electrolocation of Gnathonemus petersii (Mormyridae). We show the validity of the model (I) by demonstrating that localized spatial patterns of object induced modulations in the electric field (electric images) are comparable to experimentally mapped 2-dimensional electric images and (II) by replicating earlier key findings showing that a normalized metric of electric image width provides an unambiguous cue for distance estimation. We then show that electric images and the distance metric vary systematically when an object is moved along the trunk. These potential ambiguities with regard to localization lead us to a spatiotemporal analysis of electric images. We introduce a new temporal metric for distance estimation that is based on the normalized spatial properties of electrical images. Finally, based on a survey of exploratory behavior, we show how objects situated at the tail, a region previously neglected, cast global electric images that extend over the whole sensory epithelium of the animals. PMID- 22781956 TI - Ultrafast UV spectroscopy: from a local to a global view of dynamical processes in macromolecules. AB - The aim of this Perspective article is to cover recent developments in the application of femtosecond UV spectroscopy to understand molecular dynamics, and outlining potential future directions in this area. With several examples from recent literature the added-value of these techniques and their capability to study in real time changes in structure, dynamics and electrostatic fields of macromolecules in a site-specific fashion, as well as to uncover concerted dynamics in biomolecules, will be shown and discussed. The emerging fields of UV pulse-shaping techniques and UV optical nonlinear spectroscopies will be discussed to outline their potential to generate a novel family of coherent nonlinear spectroscopies for spectroscopic and microscopic applications. PMID- 22781957 TI - Central nervous system injury and neurobiobehavioral function in children with brain tumors: a review of the literature. AB - BACKGROUND: Children with brain tumors present a complex set of factors when considering treatment decisions, including type and location of tumor and age of the child. Two-thirds of children will survive, but historically have had poorer neurocognitive and quality-of-life outcomes when compared with survivors of other childhood cancers. Delaying or forgoing cranial radiation completely is thought to lead to improved neurobiobehavioral outcomes, but there is still relatively little research in this area. OBJECTIVES: The objectives of this study were to review and consolidate what is known about the effects of cranial radiation and chemotherapy on normal brain tissue and to synthesize that information relative to neurobiobehavioral findings in children with brain tumors. METHODS: A literature search using PubMed and PsycINFO from 2000 to 2011 was done using a variety of terms related to childhood brain tumor treatment and outcome. A total of 70 articles were reviewed, and 40 were chosen for inclusion in the review based on most relevance to this population. RESULTS: Both cranial radiation and certain chemotherapy agents cause damage to or loss of healthy neurons, as well as a decrease in the number of progenitor cells of the hippocampus. However, in general, children treated with chemotherapy alone appear to have less of a neurobiobehavioral impact than those treated with cranial radiation. CONCLUSIONS: The trend toward delaying or postponing cranial radiation when possible may improve overall neurocognitive and quality-of-life outcomes. IMPLICATIONS FOR PRACTICE: Nurses require knowledge of these issues when discussing treatment with families and with caring for long-term survivors. PMID- 22781959 TI - Cognitive neuroscience: Adapting to cognitive load. PMID- 22781958 TI - Knowing how much you don't know: a neural organization of uncertainty estimates. AB - How we estimate uncertainty is important in decision neuroscience and has wide ranging implications in basic and clinical neuroscience, from computational models of optimality to ideas on psychopathological disorders including anxiety, depression and schizophrenia. Empirical research in neuroscience, which has been based on divergent theoretical assumptions, has focused on the fundamental question of how uncertainty is encoded in the brain and how it influences behaviour. Here, we integrate several theoretical concepts about uncertainty into a decision-making framework. We conclude that the currently available evidence indicates that distinct neural encoding (including summary statistic-type representations) of uncertainty occurs in distinct neural systems. PMID- 22781960 TI - Neuroanatomy: Out with the old (model). PMID- 22781961 TI - InGaN quantum dot formation mechanism on hexagonal GaN/InGaN/GaN pyramids. AB - Growing InGaN quantum dots (QDs) at the apex of hexagonal GaN pyramids is an elegant approach to achieve a deterministic positioning of QDs. Despite similar synthesis procedures by metal organic chemical vapor deposition, the optical properties of the QDs reported in the literature vary drastically. The QDs tend to exhibit either narrow or broad emission lines in the micro-photoluminescence spectra. By coupled microstructural and optical investigations, the QDs giving rise to narrow emission lines were concluded to nucleate in association with a (0001) facet at the apex of the GaN pyramid. PMID- 22781962 TI - Effects of storage methods on time-related changes of titanium surface properties and cellular response. AB - Titanium implants are sold in the market as storable medical devices. All the implants have a certain shelf life during which they maintain their sterility, but variations of the surface properties through this duration have not been subject to a comprehensive assessment. The aim of this study was to investigate the effects of storage methods on time-related changes of titanium surface properties. Acid-etched titanium discs (Sa = 0.82 um) were placed in a sealed container (tradition method) or submerged in the ddH(2)O/NaCl solution (0.15 mol L(-1))/CaCl(2) solution (0.15 mol L(-1)), and new titanium discs were used as a control group. SEM and optical profiler showed that surface morphology and roughness did not change within different groups, but the XPS analysis confirmed that the surface chemistry altered by different storage protocols as the storage duration increased, and the contact angle also varied with storage methods. The storage method also affected the protein adsorption capacity and cellular response on the titanium surface. All titanium discs stored in the solution maintained their excellent bioactivity even after four weeks storage time, but titanium discs stored in a traditional manner decreased substantially in an age dependent manner. Much effort is needed to improve the storage methods in order to maintain the bioactivity of a titanium dental implant. PMID- 22781963 TI - Combining piracetam and lithium salts: ionic co-crystals and co-drugs? AB - Mechanochemical reaction of solid piracetam with the inorganic salts LiCl and LiBr yields ionic co-crystals which are also co-drugs, characterized by markedly different thermal properties with respect to pure components, also depending on the method for preparation and/or conditions of measurements; single crystal and powder X-ray diffraction at variable temperatures, DSC, TGA, hot stage microscopy (HSM) and intrinsic dissolution rate have been used to fully characterize the solid products. PMID- 22781964 TI - Long-timescale simulations of diffusion in molecular solids. AB - Kinetic processes play a crucial role in the formation and evolution of molecular layers. In this perspective we argue that adaptive kinetic Monte Carlo is a powerful simulation technique for determining key kinetic processes in molecular solids. The applicability of the method is demonstrated by simulating the diffusion of a CO admolecule on a water ice surface, which is an important process for the formation of organic compounds on interstellar dust grains. CO diffusion is found to follow Arrhenius behavior and the corresponding effective activation energy for diffusion is determined to be 50 +/- 1 meV. A coarse graining algorithm is applied which greatly enhances the efficiency of the simulations at low temperatures, down to 10 K, without altering the underlying physical processes. Eventually, we argue that a combination of both on- and off lattice kinetic Monte Carlo techniques is a good way for simulating large-scale processes in molecular solids over long time spans. PMID- 22781965 TI - Extreme obesity in the intensive care unit: the malignant obesity hypoventilation syndrome. PMID- 22781967 TI - Primary care of children: the unique role of GPs. PMID- 22781968 TI - What's special about medical generalism? The RCGP's response to the independent Commission on Generalism. PMID- 22781969 TI - A new approach to patients with lower urinary tract symptoms. PMID- 22781970 TI - Burnout and empathy in primary care: three hypotheses. PMID- 22781971 TI - Telling the truth: why disclosure matters in chronic kidney disease. PMID- 22781972 TI - Diagnosis and management of polymyalgia rheumatica. PMID- 22781973 TI - Impact of health system reforms on primary care research. PMID- 22781974 TI - Calling time on the 10-minute consultation [letter]. PMID- 22781975 TI - Not just another primary care workforce crisis ... [letter]. PMID- 22781976 TI - Not just another primary care workforce crisis ... [letter]. PMID- 22781977 TI - Privatisation: an exercise in ambiguity and ideology. PMID- 22781978 TI - Integrated approach to prescribing education. PMID- 22781979 TI - In preparing for the MRCGP[INT]. PMID- 22781981 TI - First do no harm: practising holistically. PMID- 22781982 TI - Outside the box: Why are Cochrane reviews so boring? PMID- 22781983 TI - 33 years of changes, and lack of changes, in US general practice. PMID- 22781984 TI - General practitioners at the deep end: the experience and views of general practitioners working in the most severely deprived areas of Scotland. PMID- 22781985 TI - Altogether now? Austerity at the Deep End. PMID- 22781988 TI - Scent of a patient: an underestimated role in clinical practice? PMID- 22781990 TI - GP commissioning: will it save money and raise standards of care? PMID- 22781991 TI - An approach to functional abdominal pain in children and adolescents. AB - For children with chronic abdominal pain, the early introduction of stress as a potential cause is likely to improve outcome. Parents underestimate their child's awareness of and capacity to worry about everyday events. Parents, children, and teachers need to be convinced that functional symptoms are a normal feature of life. The need for empathy and quality discussion between doctor, parents, and child concerning potential causes of stress is critical. All reinforcement should be removed including insistence on continued school attendance. Cognitive behavioural therapy appears to be helpful in resistant cases. Medication such as antidepressants should be avoided unless prescribed by a child psychiatrist. PMID- 22781992 TI - Group A streptococcal infections in primary care: a case report. PMID- 22781993 TI - Presenting symptoms of children with cancer: a primary-care population-based study. AB - BACKGROUND: Knowledge of how children with cancer present in general practice is sparse. Timely referral from general practice is important to ensure early diagnosis. AIM: To investigate the presenting symptoms and GPs' interpretations of symptoms of children with cancer. DESIGN AND SETTING: A Danish nationwide population-based study including children (<15 years) with an incident cancer diagnosis (January 2007 to December 2010). METHOD: A questionnaire on symptoms and their interpretation was mailed to GPs (n=363). Symptoms were classified according to the International Classification of Primary Care (ICPC)-2 classification. RESULTS: GPs' response rate was 87% (315/363) and GPs were involved in the diagnostic process of 253 (80.3%) children. Symptoms were few (2.4 per child) and most fell into the category 'general and unspecified' (71.9%), apart from patients with tumours of the central nervous system (CNS), whose symptoms fell mostly in the category 'neurological' (for example, headache). Symptoms like pain, swelling/lump, or fatigue were reported in 25% of the patients and they were the most commonly reported symptoms. GPs interpreted children's symptoms as alarm symptoms in 20.2%, as serious (that is, not alarm) symptoms in 52.9%, and as vague symptoms in 26.9%. GPs' interpretation varied significantly by diagnosis (P<0.001). CONCLUSION: Children with cancer presented with few symptoms in general practice, of which most were 'general and unspecified' symptoms. Only 20% presented alarm symptoms, while 27% presented vague and non-specific symptoms. This low level of alarm symptoms may influence the time from symptom presentation in general practice to final diagnosis. PMID- 22781994 TI - Use of folic acid supplements and risk of cleft lip and palate in infants: a population-based cohort study. AB - BACKGROUND: Orofacial clefts occur when the lips or the roof of the mouth do not fuse properly during the early weeks of pregnancy. There is strong evidence that periconceptional use of folic acid can prevent neural tube defects but its effect on oral clefts has generated debate. AIM: To identify factors associated with suboptimal periconceptional use of folic acid and its potential effect on oral clefts. DESIGN AND SETTING: The population-based infant cohort of the national Growing Up in Ireland study, which consists of 11 134 9-month-old infants. METHOD: Data collection comprised questionnaires conducted by interviewers with parents in parents' homes. Characteristics of mothers who did or did not take folic acid before and during pregnancy, as well as the effect of folic acid use on the prevalence of cleft lip and palate were recorded. RESULTS: The prevalence of cleft lip and palate was 1.98 (95% confidence interval [CI] = 1.31 to 2.99) per 1000 9-month-olds. The odds ratio for cleft lip was 4.36-fold higher (95% CI = 1.55 to 12.30, P = 0.005) for infants of mothers who did not take folic acid during the first 3 months of pregnancy, when compared with those who did have a folate intake during the first trimester. Folic acid use was suboptimal in 36.3% (95% CI = 35.4 to 37.2) of the sample. CONCLUSION: These findings support the hypothesis that taking folic acid may partially prevent cleft lip and palate. They are particularly relevant for GPs, because they are usually the first port of call for women before and during early pregnancy. PMID- 22781995 TI - Steam inhalation therapy: severe scalds as an adverse side effect. AB - BACKGROUND: Steam inhalation therapy is often recommended in the treatment of a common cold. However, it has no proven benefit and may in fact have serious adverse side effects in terms of burn injuries. AIM: To quantify the human and economic costs of steam inhalation therapy in terms of burn injury. DESIGN AND SETTING: A prospective database study of all patients admitted to the burn centres (Beverwijk, Groningen, Rotterdam) and the hospital emergency departments in the Netherlands. METHOD: Number and extent of burn injuries as a result of steam inhalation therapy were analysed, as well as an approximation made of the direct costs for their medical treatment. RESULTS: Annually, on average three people are admitted to in one of the Dutch burn centres for burns resulting from steam inhalation therapy. Most victims were children, and they needed skin grafting more often than adults. The total direct medical costs for burn centre and emergency department treatment were ?115,500 (L93,000), emotional costs are not reflected. CONCLUSION: As steam inhalation therapy has no proven benefit and the number and extent of complications of this therapy in terms of burn injury are significant, especially in children, steam inhalation therapy should be considered a dangerous procedure and not recommended anymore in professional guidelines and patient brochures. PMID- 22781996 TI - A simple approach to improve recording of concerns about child maltreatment in primary care records: developing a quality improvement intervention. AB - BACKGROUND: Information is lacking on how concerns about child maltreatment are recorded in primary care records. AIM: To determine how the recording of child maltreatment concerns can be improved. DESIGN AND SETTING: Development of a quality improvement intervention involving: clinical audit, a descriptive survey, telephone interviews, a workshop, database analyses, and consensus development in UK general practice. METHOD: Descriptive analyses and incidence estimates were carried out based on 11 study practices and 442 practices in The Health Improvement Network (THIN). Telephone interviews, a workshop, and a consensus development meeting were conducted with lead GPs from 11 study practices. RESULTS: The rate of children with at least one maltreatment-related code was 8.4/1000 child years (11 study practices, 2009-2010), and 8.0/1000 child years (THIN, 2009-2010). Of 25 patients with known maltreatment, six had no maltreatment-related codes recorded, but all had relevant free text, scanned documents, or codes. When stating their reasons for undercoding maltreatment concerns, GPs cited damage to the patient relationship, uncertainty about which codes to use, and having concerns about recording information on other family members in the child's records. Consensus recommendations are to record the code 'child is cause for concern' as a red flag whenever maltreatment is considered, and to use a list of codes arranged around four clinical concepts, with an option for a templated short data entry form. CONCLUSION: GPs under-record maltreatment related concerns in children's electronic medical records. As failure to use codes makes it impossible to search or audit these cases, an approach designed to be simple and feasible to implement in UK general practice was recommended. PMID- 22781997 TI - Missed opportunities: mental disorder in children of parents with depression. AB - BACKGROUND: Emerging evidence suggests that early intervention and prevention programmes for mental health problems in the offspring of parents with depression are important. Such programmes are difficult to implement if children with psychiatric disorder are not identified and are not accessing services, even if their parents are known to primary care. AIM: To investigate service use in children of parents who have recurrent depression, and factors that influence such contact. DESIGN AND SETTING: A total of 333 families were recruited, mainly through primary health care, in which at least one parent had received treatment for recurrent depression and had a child aged 9-17 years. METHOD: Psychiatric assessments of parents and children were completed using research diagnostic interviews. The service-use interview recorded current (in the 3 months prior to interview) and lifetime contact with health, educational, and social services due to concerns about the child's emotions or behaviour. RESULTS: Only 37% of children who met criteria for psychiatric disorder were in contact with any service at the time of interview. A third, who were suicidal or self-harming and had a psychiatric disorder at that time, were not in contact with any service. Lack of parental worry predicted lower service use, with higher rates in children with comorbidity and suicidality. CONCLUSION: Most children with a psychiatric disorder in this high-risk sample were not in contact with services. Improving ease of access to services, increasing parental and professional awareness that mental health problems can cluster in families, and improving links between adult and child services may help early detection and intervention strategies for the offspring of parents with depression. PMID- 22781998 TI - GPs' considerations in multimorbidity management: a qualitative study. AB - BACKGROUND: Scientific evidence on how to manage multimorbidity is limited, but GPs have extensive practical experience with multimorbidity management. AIM: To explore GPs' considerations and main objectives in the management of multimorbidity and to explore factors influencing their management of multimorbidity. DESIGN AND SETTING: Focus group study of Dutch GPs; with heterogeneity in characteristics such as sex, age and urbanisation. METHOD: The moderator used an interview guide in conducting the interviews. Two researchers performed the analysis as an iterative process, based on verbatim transcripts and by applying the technique of constant comparative analysis. Data collection proceeded until saturation was reached. RESULTS: Five focus groups were conducted with 25 participating GPs. The main themes concerning multimorbidity management were individualisation, applying an integrated approach, medical considerations placed in perspective, and sharing decision making and responsibility. A personal patient-doctor relationship was considered a major factor positively influencing the management of multimorbidity. Mental-health problems and interacting conditions were regarded as major barriers in this respect and participants experienced several practical problems. The concept of patient-centredness overarches the participants' main objectives. CONCLUSION: GPs' main objective in multimorbidity management is applying a patient-centred approach. This approach is welcomed since it counteracts some potential pitfalls of multimorbidity. Further research should include a similar design in a different setting and should aim at developing best practice in multimorbidity management. PMID- 22782000 TI - James Mackenzie Lecture 2011: multimorbidity, goal-oriented care, and equity. PMID- 22781999 TI - Barriers to GPs' use of evidence-based medicine: a systematic review. AB - BACKGROUND: GPs report various barriers to the use and practice of evidence-based medicine (EBM). A review of research on these barriers may help solve problems regarding the uptake of evidence in clinical outpatient practice. AIM: To determine the barriers encountered by GPs in the practice of EBM and to come up with solutions to the barriers identified. DESIGN: A systematic review of the literature. METHOD: The following databases were searched: MEDLINE (PubMed), Embase, CINAHL, ERIC, and the Cochrane Library, until February 2011. Primary studies (all methods, all languages) that explore the barriers that GPs encounter in the practice of EBM were included. RESULTS: A total of 14 700 articles were identified, of which 22 fulfilled all inclusion criteria. Of the latter, nine concerned qualitative, 12 concerned quantitative, and one concerned both qualitative and quantitative research methods. The barriers described in the articles cover the categories: evidence (including the accompanying EBM steps), the GP's preferences (experience, expertise, education), and the patient's preferences. The particular GP setting also has important barriers to the use of EBM. Barriers found in this review, among others, include lack of time, EBM skills, and available evidence; patient-related factors; and the attitude of the GP. CONCLUSION: Various barriers are encountered when using EBM in GP practice. Interventions that help GPs to overcome these barriers are needed, both within EBM education and in clinical practice. PMID- 22782001 TI - Measuring continuity of care: psychometric properties of the Nijmegen Continuity Questionnaire. AB - BACKGROUND: Recently, the Nijmegen Continuity Questionnaire (NCQ) was developed. It aims to measure continuity of care from the patient perspective across primary and secondary care settings. Initial pilot testing proved promising. AIM: To further examine the validity, discriminative ability, and reliability of the NCQ. DESIGN: A prospective psychometric instrument validation study in primary and secondary care in the Netherlands. METHOD: The NCQ was administered to patients with a chronic disease recruited from general practice (n = 145) and hospital outpatient departments (n = 123) (response rate 76%). A principal component analysis was performed to confirm three subscales that had been found previously. Construct validity was tested by correlating the NCQ score to scores of other scales measuring quality of care, continuity, trust, and satisfaction. Discriminative ability was tested by investigating differences in continuity subscores of different subgroups. Test-retest reliability was analysed in 172 patients. RESULTS: Principal factor analysis confirmed the previously found three continuity subscales - personal continuity, care provider knows me; personal continuity, care provider shows commitment; and team/cross-boundary continuity. Construct validity was demonstrated through expected correlations with other variables and discriminative ability through expected differences in continuity subscores of different subgroups. Test-retest reliability was high (the intraclass correlation coefficient varied between 0.71 and 0.82). CONCLUSION: This study provides evidence for the validity, discriminative ability, and reliability of the NCQ. The NCQ can be of value to identify problems in continuity of care. PMID- 22782002 TI - Inferring differences in the distribution of reaction rates across conditions. AB - Elucidating changes in the distribution of reaction rates in metabolic pathways under different conditions is a central challenge in systems biology. Here we present a method for inferring regulation mechanisms responsible for changes in the distribution of reaction rates across conditions from correlations in time resolved data. A reversal of correlations between conditions reveals information about regulation mechanisms. With the use of a small in silico hypothetical network, based on only the topology and directionality of a known pathway, several regulation scenarios can be formulated. Confronting these scenarios with experimental data results in a short list of possible pathway regulation mechanisms associated with the reversal of correlations between conditions. This procedure allows for the formulation of regulation scenarios without detailed prior knowledge of kinetics and for the inference of reaction rate changes without rate information. The method was applied to experimental time-resolved metabolomics data from multiple short-term perturbation-response experiments in S. cerevisiae across aerobic and anaerobic conditions. The method's output was validated against a detailed kinetic model of glycolysis in S. cerevisiae, which showed that the method can indeed infer the correct regulation scenario. PMID- 22782003 TI - Recent advances in osteoarthritis imaging--the osteoarthritis initiative. AB - Osteoarthritis (OA) is the most common joint disorder. The osteoarthritis initiative (OAI) is a multicentre, longitudinal, prospective observational cohort study of knee OA that aims to provide publicly accessible clinical datasets, images and biospecimens, to enable researchers to investigate factors that influence the onset and development of OA, and evaluate biomarkers that predict and track the course of the disease. In this Perspectives, we describe the rationale and design of the OAI and its cohort, discuss imaging protocols and summarize image analyses completed to date. We include descriptive analyses of publicly available longitudinal (2-year) data of changes in cartilage thickness in a core sample of 600 knees from 590 participants in the OAI progression subcohort. Furthermore, we describe published methodological and applied imaging research that has emerged from OAI pilot studies and OAI data releases, and how these studies might contribute to clinical development of biomarkers for assessing the efficacy of intervention trials. PMID- 22782004 TI - Paediatric rheumatic disease: lessons from SLE: children are not little adults. PMID- 22782005 TI - Bone: modulation of IGF-1 might prevent osteoporosis. PMID- 22782006 TI - Recognizing and treating secondary osteoporosis. AB - Osteoporosis, through its association with fragility fracture, is a major public health problem, costing an estimated $34.8 billion worldwide per annum. With projected demographic changes, the burden looks set to grow. Therefore, the prevention of osteoporosis, as well as its identification and treatment once established, are becoming increasingly important. Osteoporosis is secondary when a drug, disease or deficiency is the underlying cause. Glucocorticoids, hypogonadism, alcohol abuse and malnutrition are among the most frequently recognized causes of secondary osteoporosis but the list of implicated diseases and drugs is growing and some of the more recently recognized associations, such as those with haematological conditions and acid-suppressing medications, are less well publicized. In some cases, advancement in treatment of the primary disease has led to people living long enough to develop secondary osteoporosis; for example, successful treatment for breast and prostate malignancies by hormonal manipulation, improved survival in HIV with the advent of anti retroviral therapies, and improved treatment for cystic fibrosis. This Review emphasizes the importance of secondary osteoporosis, discusses familiar and less well-known causes and what is known of their mechanisms, provides guidance as to the pragmatic identification of secondary osteoporosis and summarizes treatment options, where available. PMID- 22782007 TI - Regenerative medicine in rheumatic disease-progress in tissue engineering. AB - Joint destruction occurs in both osteoarthritis and rheumatoid arthritis. Even in the era of biologic agents, this destruction can be delayed but not averted. As cartilage has limited ability to self-regenerate, joint arthroplasty is required. Here, we outline current tissue engineering procedures (including autologous chondrocyte implantation and in situ mesenchymal stem cell recruitment) that are routinely applied for the regenerative treatment of injured or early osteoarthritic cartilage. Potential future regenerative therapies, including administration of multipotent or pluripotent stem cells, are also discussed. In the future, cell-free, material-based (for cartilage lesions) or cell-free, factor-based (for osteoarthritic cartilage) therapies to facilitate the recruitment of repair cells and improve cartilage metabolism are likely to become more important. Moreover, delivery of anti-inflammatory factors or immunomodulatory cells could be a regenerative treatment option for rheumatoid arthritis. Tissue engineering faces a crucial phase to translate products into clinical routine and the regulatory framework for cell-based products in particular is an important issue. PMID- 22782009 TI - Effect of pre rigor stretching on beef tenderness development. AB - The objective of this study was to determine effects of pre rigor stretching on beef tenderness development. Beef loins (M. longissimus dorsi; n=24) were assigned to either stretching or non-stretching treatments and aged for 14 days at -1.5 degrees C. Sarcomere length, shear force, water-holding capacity and proteolysis were determined for the loins at 1, 7 and 14 days of ageing. Stretching increased the length of the loins by 33% resulting in a trend of increasing sarcomere length (P=0.19). However, no significant differences for shear force values, purge, drip and cooking losses between treatments were found. Shear force values decreased with ageing times (P<0.05). Western blot assay found that stretching did not affect the extent of desmin degradation. The findings from the present study suggest that pre rigor stretching with the current increase in length will not contribute to tenderness improvement of the beef loins. PMID- 22782010 TI - Development and validation of a real-time PCR assay specific for Clostridium estertheticum and C. estertheticum-like psychrotolerant bacteria. AB - A new real-time PCR assay was developed targeted to the psychrotolerant spoilage bacteria, Clostridum estertheticum, a causative agent of 'blown-pack' spoilage of vacuum packaged meats during chilled storage. Further, a robust validation of the sensitivity and specificity in different meat processing related matrices was carried out. Results show that real-time PCR is a valid method for the detection of C. estertheticum spores as long as consideration is given to the matrix being tested and the sensitivity of detection required. For meat, hide, blood/drip and environmental swabs it was possible to detect low numbers of C. estertheticum spores (approx 3 spores per ml) by direct real-time PCR (without pre-enrichment of the samples). For faeces and soil matrices, a cold temperature enrichment step was required prior to DNA extraction and real-time PCR analysis to increase the ability to detect samples containing C. estertheticum spores; this was particularly important when the samples contained low numbers of spores (less than 3 spores per ml). For matrices with high levels of PCR inhibitors such as soil, it was necessary to dilute the extracted DNA sample 100 fold especially for detection of high levels of contamination (greater than 103 per ml) otherwise a pre-enrichment was required. PMID- 22782011 TI - Cosmetic products: learning to read labels. AB - Reading the labels of cosmetic products often proves difficult as mandatory labelling information is mixed with non-obligatory and sometimes misleading data, which is included on the labels according to the manufacturer's wishes. This article aims at clarifying the labelling information provided for by the new European Regulation on cosmetic products that will come into effect in 2013 and on the non-regulated but frequently seen information on the packaging of cosmetic products. PMID- 22782008 TI - The pathogenesis, diagnosis and treatment of Raynaud phenomenon. AB - The past 10 years have seen the publication of results from several multicentre clinical trials in primary and systemic sclerosis (SSc)-related Raynaud phenomenon. The publication of these studies has occurred as a result of new insights into the pathogenesis of Raynaud phenomenon, which are directing new treatment approaches, and increased international collaboration between clinicians and scientists. Although the pathogenesis of Raynaud phenomenon is complex, abnormalities of the blood vessel wall, of neural control mechanisms and of intravascular (circulating) factors are known to interact and contribute. Key players relevant in drug development include nitric oxide, endothelin-1, alpha adrenergic receptor activation, abnormal signal transduction in vascular smooth muscle, oxidative stress and platelet activation. The main advances in diagnosis have been a clearer understanding of autoantibodies and of abnormal nailfold capillary patterns as independent predictors of SSc, and widespread use and increased availability of capillaroscopy. The ultimate aim is to translate the advances made in the pathophysiology and early diagnosis into development of treatments to prevent and reverse digital vascular dysfunction and injury. This Review provides an update of the pathogenesis, diagnosis and treatment of Raynaud phenomenon. Current and future treatment approaches are discussed, and some key unanswered questions are highlighted. PMID- 22782012 TI - Effect of alginate hydrogel containing polyproline-rich peptides on osteoblast differentiation. AB - Polyproline-rich synthetic peptides have previously been shown to induce bone formation and mineralization in vitro and to decrease bone resorption in vivo. Alginate hydrogel formulations containing these synthetic peptides (P2, P5, P6) or Emdogain(r) (EMD) were tested for surface coating of bone implants. In an aqueous environment, the alginate hydrogels disclosed a highly compact structure suitable for cell adhesion and proliferation. Lack of cytotoxicity of the alginate-gel coating containing peptides was tested in MC3T3-E1 cell cultures. In the present study, relative mRNA expression levels of integrin alpha 8 were induced by P5 compared to untreated alginate gel, and osteopontin mRNA levels were increased after 21 days of culture by treatment with synthetic peptides or EMD compared to control. Further, in agreement with previous results when the synthetic peptides were administered in the culture media, osteocalcin mRNA was significantly upregulated after long-term treatment with the formulated synthetic peptides compared to untreated and EMD alginate gel. These results indicate that the alginate gel is a suitable carrier for the delivery of synthetic peptides, and that the formulation is promising as biodegradable and biocompatible coating for bone implants. PMID- 22782014 TI - Cu-SSZ-39, an active and hydrothermally stable catalyst for the selective catalytic reduction of NOx. AB - A Cu-exchanged SSZ-39 zeolite has been synthesized and tested for the selective catalytic reduction (SCR) of NOx. This material shows an excellent catalytic activity, and most importantly, an extraordinary hydrothermal stability. PMID- 22782015 TI - Classical toy models for the monopole shift and the quadrupole shift. AB - The penetration of s- and p(1/2)-electrons into the atomic nucleus leads to a variety of observable effects. The presence of s-electrons inside the nucleus gives rise to the isotope shift in atomic spectroscopy, and to the isomer shift in Mossbauer spectroscopy. Both well-known phenomena are manifestations of the more general monopole shift. In a recent paper (Koch et al., Phys. Rev. A, 2010, 81, 032507), we discussed the existence of the formally analogous quadrupole shift: a tensor correction to the electric quadrupole interaction due to the penetration of relativistic p(1/2)-electrons into the nucleus. The quadrupole shift is predicted to be observable by high-accuracy molecular spectroscopy on a set of 4 molecules (the quadrupole anomaly). The simple physics behind all these related phenomena is easily obscured by an elaborate mathematical formalism that is required for their derivation: a multipole expansion in combination with perturbation theory, invoking quantum physics and ideally relativity. In the present paper, we take a totally different approach. We consider three classical 'toy models' that can be solved by elementary calculus, and that nevertheless contain all essential physics of the monopole and quadrupole shifts. We hope that this intuitive (yet exact) analysis will increase the understanding about multipole shift phenomena in a broader community. PMID- 22782013 TI - Epigenetic mechanisms governing the process of neurodegeneration. AB - Studies elucidating how and why neurodegeneration unfolds suggest that a complex interplay between genetic and environmental factors is responsible for disease pathogenesis. Recent breakthroughs in the field of epigenetics promise to advance our understanding of these mechanisms and to promote the development of useful and effective pre-clinical risk stratification strategies, molecular diagnostic and prognostic methods, and disease-modifying treatments. PMID- 22782016 TI - Mini-laparoscopy in the endoscopy unit. AB - PURPOSE OF REVIEW: The evaluation of liver histology is an important component of the diagnosis and staging of liver diseases. The most common technique employed to sample liver tissue for decades has been percutaneous liver biopsy. Although this is a relatively well tolerated technique in the early stages of liver disease, it carries a high risk of complications, particularly hemorrhage, in patients with advanced cirrhosis. Mini-laparoscopy allows macroscopic assessment and biopsy under direct vision and therefore is a well tolerated and effective technique. RECENT FINDINGS: The major advantages of this technique are direct visualization of the liver surface, thereby allowing inspection for morphologic changes of cirrhosis as well as targeted biopsies, the ability to immediately treat potential complications (bleeding and bile leakage), furthermore the peritoneal cavity can be visualized to stage gastrointestinal (GI) malignancies. Additionally, 'blind' percutaneous liver biopsy fails to establish a diagnosis in about 25% of cases, largely because of sampling error. SUMMARY: This technique presents the opportunity to visualize the surface of the liver and the peritoneal cavity, making it a valuable tool for liver biopsy. This review summarizes the technique of mini-laparoscopy and addresses its potential uses and limitations as a diagnostic modality. PMID- 22782017 TI - Update on biliary and pancreatic sphincterotomy. AB - PURPOSE OF REVIEW: To summarize the indications, success rates and complications associated with endoscopic sphincterotomy and endoscopic balloon dilation (EBD). RECENT FINDINGS: Pancreatic and/or biliary sphincterotomies are essential components of most current therapeutic endoscopic retrograde cholangiopancreatography (ERCP). A current large body of evidence has established biliary sphincterotomy as effective in extraction of bile duct stones. The most common complications of biliary sphincterotomy are post-ERCP pancreatitis, as well as acute or delayed hemorrhage, the risks for which can be stratified according to well described patient and procedure related factors. Evidence is accumulating that pancreatic sphincterotomy is useful in at least some settings for treatment of sphincter of Oddi dysfunction, chronic pancreatitis, and pancreas divisum. EBD provides an adjunct or an alternative to biliary sphincterotomy for extraction of stones from the bile duct when routine biliary sphincterotomy is inadequate or risk excessive. SUMMARY: Sphincterotomy and EBD are useful in managing a variety of pancreatobiliary conditions. Attention to risks of these procedures is essential for their efficacy and safety. PMID- 22782019 TI - Neurohormonal regulation of pancreatic secretion. AB - PURPOSE OF REVIEW: Recent advances in the regulation of pancreatic secretion by neural and hormonal mechanisms are discussed in this review. RECENT FINDINGS: It has been shown that the multidrug-resistance protein MRP4 may play a role in the efflux of cAMP from exocrine cells and neurokinin receptors are important in substance P-mediated inhibition of ductal bicarbonate secretion. Leptin attenuates glucagon secretion by downregulating glucagon gene expression, whereas ghrelin upregulates glucagon release by elevating intracellular calcium and phosphorylation of extracellular signal-regulated kinase (ERK). Cytokine interleukin 6 is secreted from muscles during exercise and induces the release of GLP-1 that stimulates insulin secretion. Osteocalcin and 17beta-estradiol mediate their effects through G protein-coupled receptors, resulting in ERK phosphorylation and activation of protein kinase-dependent signaling pathways. Melatonin and ghrelin inhibit insulin secretion through inhibitory G proteins, whereas aldosterone may attenuate insulin secretion by increasing oxidative stress in islets cells. Finally, the pattern of innervation of human pancreatic islets has been examined and demonstrated to be very different from that in the mouse. SUMMARY: Many different receptors and signaling pathways govern the complex biology of pancreatic secretion. Elucidation of these cellular mechanisms will aid in drug discovery and treatment as well as prevention of pancreatic diseases. PMID- 22782020 TI - Pancreatic surgery for adenocarcinoma. AB - PURPOSE OF REVIEW: Pancreatic resection remains among the most formidable and complex of abdominal surgical operations. Nonetheless, recent observations have continued to provide incremental improvement in both our evidence for treatment regimens and the technology, resulting in better outcomes. RECENT FINDINGS: Neoadjuvant regimens appear to have promise, at least in local control and perhaps in long-term survival. More extensive operations focusing on perineural invasion along with minimally invasive laparoscopic and robotic techniques are attracting increasing attention. The effectiveness of major vascular resection remains controversial. Concentration of patients in centers of expertise has contributed to improved outcomes. SUMMARY: Improved management of pancreatic resections for cancer with more extensive and less-invasive surgical techniques has increased the number of patients who are candidates for effective surgical treatment. PMID- 22782018 TI - Chronic pancreatitis. AB - PURPOSE OF REVIEW: We review important new clinical observations in chronic pancreatitis reported in 2011. RECENT FINDINGS: Smoking increases the risk of nongallstone acute pancreatitis and the progression of acute pancreatitis to chronic pancreatitis. Binge drinking during Oktoberfest did not associate with increased hospital admissions for acute pancreatitis. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in chronic pancreatitis is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90 000 United States Pharmacopeia units of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared with endoscopic treatment in patients advanced chronic pancreatitis with a dilated main duct +/- pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with chronic pancreatitis but approximately 30% of patients have significant side effects. SUMMARY: Patients with nongallstone-related acute pancreatitis or chronic pancreatitis of any cause should cease smoking. Results of this year's investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in chronic pancreatitis, and the mechanisms and treatment of neuropathic pain in chronic pancreatitis. PMID- 22782022 TI - A novel strategy for controllable emissions from Eu3+ or Sm3+ ions co-doped SrY2O4:Tb3+ phosphors. AB - Trivalent rare-earth (RE) ions (Eu(3+), Tb(3+) and Sm(3+)) activated multicolor emitting SrY(2)O(4) phosphors were synthesized by a sol-gel process. The structural and morphological studies were performed by the measurements of X-ray diffraction profiles and scanning electron microscope (SEM) images. The pure phase of SrY(2)O(4) appeared after annealing at 1300 degrees C and the doping of RE ions did not show any effect on the structural properties. From the SEM images, the closely packed particles were observed due to the roughness of each particle tip. The photoluminescence (PL) analysis of individual RE ions activated SrY(2)O(4) phosphors exhibits excellent emission properties in their respective regions. The Eu(3+) co-activated SrY(2)O(4):Tb(3+) phosphor creates different emissions by controlling the energy transfer from Tb(3+) to Eu(3+) ions. Based on the excitation wavelengths, multiple (green, orange and white) emissions were obtained by Sm(3+) ions co-activated with SrY(2)O(4):Tb(3+) phosphors. The decay measurements were carried out for analyzing the energy transfer efficiency and the possible ways of energy transfer from donor to acceptor. The cathodoluminescence properties of these phosphors show similar behavior as PL properties except the energy transfer process. The obtained results indicated that the energy transfer process was quite opposite to the PL properties. The calculated CIE chromaticity coordinates of RE ions activated SrY(2)O(4) phosphors confirmed the red, green, orange and white emissions. PMID- 22782021 TI - Advances in the diagnosis of cystic neoplasms of the pancreas. AB - PURPOSE OF REVIEW: Management of pancreatic cystic neoplasms is challenging due to limitations of current diagnostic tests. There is considerable interest in developing an accurate and cost-effective diagnostic test (or panel of tests) to differentiate cyst types and to identify those which would benefit most from surgical resection. RECENT FINDINGS: Current multidetector computed tomography scans may have improved accuracy to distinguish between mucinous and nonmucinous cysts. Attempts to generate quantitative criteria from cross-sectional imaging to differentiate cyst types have yielded mixed results. DNA mutations and microRNA show promise in the ability to distinguish between mucinous and nonmucinous cysts. Cyst fluid mucin glycoproteins and cytokines may identify those cysts with high malignant potential. Proteomic analysis may yield other biomarker candidates. SUMMARY: Analysis of DNA mutations and proteins within pancreatic cyst fluid have identified potential biomarkers to aid with the management of patients with pancreatic cystic neoplasms. PMID- 22782023 TI - [Analysis of narcotic drugs in ancient times]. AB - Recordings about narcotic drugs could be found in Liezi.Tangwen, and since then narcotic drugs for medical use appeared often in literature. In the South and North Song Dynasties, narcotic drugs were abused by the people. Various drugs like knock-out drops and knock-out incense appeared at that time and were forbidden by the government. From then on, narcotic drugs for medical use kept developing while the development history of folk narcotic drugs was not clear. There were a variety of formulas for narcotic drugs in TCM and the formula of folk narcotic drugs was simple. Gancaodou decoction was the antidote for TCM narcotic drugs while the antidote for folk narcotic drugs was cold water. Later the TCM narcotic drugs were also used less and less because of the side effects, prohibition of the government and the pressure from introduction of western medicine. Studies of recent years show that many dosage methods for narcotic drugs have been developed (such as oral drugs, enema drugs, injection and intravenous drugs) and the understanding of narcotic drugs deepens, which is good for the reapplication and popularization of narcotic drugs. PMID- 22782024 TI - [Evolution of the Efficacy of Fu-pen-zi and the Reason]. AB - Fu-pen-zi had been used as a reinforcing drug in medical literature and compatibility formulas before the book Bencao Yanyi was finished. Bencao Yanyi first mentioned that Fu-pen-zi was effective for incontinence, and this function was used to explain the meaning of its name. Doctors in later ages accepted this theory and began to use Fu-pen-zi as an astringent drug. In modern times, Fu-pen zi is classified to astringent drugs in various editions of the Chinese materia medica textbook. The change of its classification may be relevant to the changes of its sources, maturity of the fruit and the part to be used. PMID- 22782025 TI - [Doctors' social rescueactions taken for plagues in the Ming dynasty]. AB - During the 277-year long history of the Ming dynasty (1368 - 1644), 75 plagues occurred in 54 years. People helping patients at that time included medical officials and folk doctors, even some Confucian scholars, officials and nobles who learned medicine assisted with disease control. Besides official free medical help, many other measures were taken, such as free herbs, free porridge and coffins. There were also other charitable acts, for example, the nobles or officials volunteered to employ doctors to help patients. By contrast, there were also some doctors who were afraid of plagues and would not like to assist patients. Concerning the effect of the rescue activities, recordings such as 'reviving many people' and 'quacks killing patients' could both be found. Limited by the medical level at that time, measures like evacuating and moving people to other places had to be taken when plagues could not be controlled. PMID- 22782026 TI - [Pharmacological research on Chinese materia medica in Modern China and TCM]. AB - The experimental pharmacological research on Ma-Huang and Tang-Kuei (Danggui) by Chen Kokuei and his colleagues in 1923, is the proem of scientific research on Chinese materia medica (CMM) in China. In the 1930's, a number of scientific research institutions were established in China, such as, the Institute of Physiology, National Academy of Peiping and the pharmaceutical laboratory of the experimental hygiene station, National Economic Council. Experts undertook extensive research on CMM. They injected the rough extractum or purified active constituent in laboratory animals to observe the characteristics of drugs and published a series of treatises. They made experimental objectives and selected experimental herbs according to TCM theory. Their inheritance and innovation in the research demonstrated better rationality than simultaneous overseas scholars to whom they were therefore superior. PMID- 22782027 TI - [TCM societies in Shanghai during the first half of the 20(th) century]. AB - In the first half of the 20(th) century, with the introduction of western academic thought and the assemblage of TCM doctors of different factions, the variety of cultures provided an ideological and academic background for TCM societies in Shanghai in modern times. Under the pressure of banning and exclusion, protective measures taken by the TCM circles promoted the establishment of TCM societies. The establishment and development of TCM societies in Shanghai in modern times included four stages - the embryonic stage (1903 - 1911), the development stage (1912 - 1926), the struggling stage (1927 - 1937) and the recovery stage (1938 - 1949). Aiming at academic studies, TCM societies in the early time could be divided into a national society and local societies and both were composed of scholars with the same academic viewpoints. Societies in the later stages aimed at maintaining status and fighting for rights. Activities held by these societies included starting publications, compiling textbooks, publishing, establishing hospitals and schools, prevention and control of infectious disease and innovation of TCM dosage forms. In the first half of the 20(th) century, the influence of TCM societies helped Shanghai become the TCM center in modern times. PMID- 22782028 TI - [Historical review of heart transplantation]. AB - In 1905, Carrel and Guthrie reported the heterotopic heart transplantation on dogs for the first time. In the same year, Shone advanced the transplantation immunity theory which provided a basis for organ transplantation. In 1964, Hardy and his colleagues performed the first human chimpanzee heart transplantation. In 1967, Barnard performed the first human-to-human orthotopic heart transplantation in the world. In 1968 - 1971, 56 hospitals performed 180 heart transplantations world-wide. But because of the poor survival rate after operation, heart transplantations became less frequent. In 1972, Castaneda and Reitz summed up the experiences of heart-lung experimental transplantation, which laid a foundation for human heart-lung transplantation. In 1973, Caves invented myocardium biopsy for rejection surveillance after heart transplantation, which solved the problem of diagnosis for early rejection. In 1981, Stanford University first took cyclosporin A into clinical practice. The acute rejection after heart transplantation was effectively controlled and the long-term survival rate was significantly increased. Heart transplantation entered the second peak period. The launching of Asian heart transplantation began in 1968. Juro.Wada with his medical team performed the first heart transplantation in Japan. In 1978, Zhang Shize in Shanghai performed the first heart transplantation in China. PMID- 22782029 TI - [Textual research of Bencaogangmu Yizhilu]. AB - Bencaogangmu Yizhilu was compiled by DAI Baoyuan according to Bencao Gangmu in the late Qing dynasty. Due to the limited circulation of the book, it was little studied by people in later ages. Errors could be found concerning the book's content, editions and the author's life. After in-depth research, we concluded that the author's name was Baoyuan (courtesy name Xintian and pseudonym Shouyu). He was born about in 1818 and the year of death was unclear. Compilation of the book was completed in 1885 and the book was published in 1887. Recording 2240 kinds of herbs, the book included 8 volumes, 7 of which were text and the 8(th) volume was the index. It has two editions-the Wu Yuansi added Shanfang printed edition (the 13th year of the Guangxu Period, 1887) and the copy edition of the Qing dynasty. PMID- 22782030 TI - [Prelimilary Study on Manipulative Resetting Pictures of Shang ke hui zuan (Collected Compilation of Traumatology)]. AB - Shang ke hui zuan (Collected Compilation of Traumatology) written by Hu Ting guang, a famous doctor in the Qing Dynasty, is a comprehensive traumatology book, which records 16 manual reduction pictures with a five-word verse in each one and 9 seven-word verses in Chapter 3 supplementing the former and vice versa. Vivid pictures and brief verses matched with each other are convenient to imitate and recite, and play a vital role in promotion of inheritance and transmission of manual reduction technique on traumatology. PMID- 22782031 TI - Development of poly(anhydride) nanoparticles loaded with peanut proteins: the influence of preparation method on the immunogenic properties. AB - Allergen-specific immunotherapy is based on the administration of allergens with the main disadvantage of inducing an allergic reaction. Within this context, we report the generation of an adjuvant and allergen-delivery system for peanut allergen immunotherapy with reduced IgE induction. Therefore, we prepared and characterized poly(anhydride) nanoparticles loaded with peanut proteins using the solvent displacement method, with some modifications in the manufacturing process. The precipitation of polymer was performed with either a mixture of ethanol and water or water. The resultant nanoparticles were dried by either freeze-drying or spray-drying, respectively. Poly(anhydride) nanoparticles loaded with peanut proteins were successfully developed, achieving both high encapsulation efficiency (70-80%) and manufacturing yield (60-80%). After intradermal immunization of mice (C57Bl/6) with peanut proteins incorporated into poly(anhydride) nanoparticles, a strong mixed T(H)1/T(H)2-type immune response was observed. Furthermore, we also provide, to our knowledge for the first time, clear evidence of the influence of formulation design on the immunostimulatory properties of nanoparticles. Taken together, our findings indicate that poly(anhydride) nanoparticles are efficient stimulators of immune responses and promising adjuvants and allergen-delivery systems applied for immunotherapy. PMID- 22782033 TI - Attending skills for dentists. PMID- 22782032 TI - Electronic and optoelectronic nano-devices based on carbon nanotubes. AB - The discovery and understanding of nanoscale phenomena and the assembly of nanostructures into different devices are among the most promising fields of material science research. In this scenario, carbon nanostructures have a special role since, in having only one chemical element, they allow physical properties to be calculated with high precision for comparison with experiment. Carbon nanostructures, and carbon nanotubes (CNTs) in particular, have such remarkable electronic and structural properties that they are used as active building blocks for a large variety of nanoscale devices. We review here the latest advances in research involving carbon nanotubes as active components in electronic and optoelectronic nano-devices. Opportunities for future research are also identified. PMID- 22782034 TI - Benefits versus risks of aspirin in cardioprotection: dangers of heart attack after discontinuation. PMID- 22782035 TI - Indirect mandibular implant-supported overdenture technique. PMID- 22782036 TI - Matrices--is achieving a tight contact still an issue? PMID- 22782037 TI - "Best dental". PMID- 22782038 TI - Bleeding on probing: what does it mean? AB - A major part of the comprehensive periodontal examination involves the assessment and recording of bleeding on probing (BOP). Many factors can influence bleeding, including medications, systemic diseases, and smoking. A review of classic and current literature is presented, discussing the role of BOP as a clinical parameter in periodontics. PMID- 22782039 TI - Combining perio-restorative protocols to maximize function. AB - This article describes a team approach for periodontal and restorative treatment intended to produce a predictable, biologically sound outcome that preserves more supporting bone and restores carious and broken down teeth. The goal of periodontal treatment, when performed in conjunction with restorative dentistry, is to provide restorative dentists with a high percentage of tooth structure that allows for a supragingival margin. An equally important goal is to ensure that an adequate thickness of connective tissue exists to create an environment more resistant to trauma and inflammation. The team approach consists of a restorative phase and a surgical phase. The restorative phase involves preparation with complete caries removal, adhesive core buildups, and provisionalization. The surgical phase involves biologic shaping of the roots and judicious osseous resection. Case studies are used to demonstrate the team approach. PMID- 22782040 TI - Diagnosis and management of vertical bony defects in periodontal disease. AB - This article discusses the diagnosis and treatment of vertical bony defects in patients with periodontitis. Defect- and tooth-related factors that impact treatment decisions and prognosis of regenerative therapy are reviewed. Etiologic and contributing factors are also discussed, as are follow-up and long-term maintenance of treated sites. PMID- 22782041 TI - The effectiveness of scaling and root planing with adjunctive time-release minocycline using an open and closed approach for the treatment of periodontitis. AB - The purpose of this study was to determine the effectiveness of scaling and root planing using a closed and open approach (papilla reflection) with and without a locally delivered antibiotic (minocycline hydrochloride microspheres) in the treatment of moderate to advanced chronic periodontitis. Twenty-five periodontal recall patients with four or more probing depths of 5.0 to 9.0 mm and bleeding on probing (BOP) participated in this double-blind trial. Each of four sites per patient was randomly assigned a different treatment: scaling/root planing only; scaling/root planing followed by minocycline placement; gingival papilla reflection followed by scaling/root planing and flap closure; and gingival papilla reflection, scaling/root planing, minocycline placement, and flap closure. At baseline and each subsequent appointment, probing depth, BOP, and clinical crown length were recorded. Patients returned at three months for measurements and supportive periodontal therapy, and at six months for final measurements. Patients followed their usual oral hygiene regimens. Data were analyzed for significant differences using a repeated measure ANOVA and a Student t-test. All treatments resulted in reduction of probing depths (average of 1.76 mm) and a marked reduction in BOP at six months. While the papilla reflection plus minocycline showed the greatest reduction in probing depth (1.91 mm) and the greatest decrease in BOP (20% at three months and 28% at six months), the differences were not significant (p > 0.05). Clinical crown lengths did not change significantly in the treatment sites; therefore, improvements in probing depth can be attributed to improved clinical attachment levels (long junctional epithelium). The combination therapies did not differ significantly from scaling/root planing alone in decreasing probing depths and BOP. PMID- 22782042 TI - Gingival recession associated with noncarious cervical lesions: combined periodontal-restorative approach and the treatment of long-term esthetic complications. AB - Buccal gingival recession is a prevalent problem in populations with a high standard of oral hygiene and is often associated with noncarious cervical lesions (NCCLs), leading to the need for a combined periodontal-restorative approach for better esthetic and functional results. In the literature, resin-modified glass ionomer (RMGI) restorations associated with periodontal surgery have been shown to achieve significant root coverage and reduction of dentin sensitivity; however, changes to the color of some of those restorations have been observed, which could compromise esthetics. Therefore, the aim of the present case report is to describe and discuss the current understanding of treatment for a gingival recession associated with an NCCL with a periodontal-restorative approach, and to describe treatment of RMGI color alteration problems two years after treatment. PMID- 22782043 TI - Drug-induced gingival overgrowth: a case report. AB - A variety of systemic drugs can lead to adverse effects in the oral environment. This article reports the case of a 61-year-old man who had a severe drug-induced gingival overgrowth (DIGO) caused by nifedipine. DIGO is relevant due to severe gingival enlargement, which causes disfigurement and blocks physiological and social functions such as mastication and speaking. Management of DIGO is always a challenge due to the patient's systemic condition. This article shows, step-by step, how the treatment was executed and how the DIGO was reversed. PMID- 22782044 TI - Cervicofacial necrotizing fasciitis following periodontal abscess. AB - Soft tissue infections are characterized by acute inflammation, diffuse edema, and suppuration, and are often associated with symptoms such as malaise, fever, tachycardia, and chills. Necrotizing fasciitis is a destructive bacterial infection affecting subcutaneous tissue and superficial fascia and is associated with high rates of mortality. It usually involves the abdomen and extremities, but it also can occur in the head and neck. Early diagnosis is critical and the most commonly accepted treatment includes radical surgical intervention and administration of broad-spectrum antibiotics. This article reports and discusses the case of a patient with odontogenic cervicofacial necrotizing fasciitis, and emphasizes the importance of early and effective treatment. PMID- 22782046 TI - Drug abuse identification and pain management in dental patients: a case study and literature review. AB - Properly identifying patients with a history of drug abuse is the first step in providing effective dental care. Dental professionals need to be fully aware of the challenges associated with treating this population. In the current study, the authors analyzed the physical and oral manifestations of illicit drug abuse to aid in the identification of patients who abuse drugs and the pain management strategies needed to treat them. The authors also present a clinical case of a patient with unique skin lesions and discuss the typical clinical findings of drug abuse based on a literature review. PMID- 22782045 TI - Effect of sweetening agents in acidic beverages on associated erosion lesions. AB - Accurate diagnosis of erosion defects caused by acidic beverages is essential when designing a comprehensive management strategy that includes combating possible recurrence. The manifestations of erosion lesions associated with acidic beverages are diverse, as seen in the differences and similarities of lesions associated with various regular and diet varieties of beverages. Erosion lesions caused by regular sugar-sweetened beverages display signs similar to dental caries, while lesions resulting from diet, non-sugar-sweetened soft drinks have defects similar to mechanical wear of the dentition. Aggravating factors such as toothbrushing or compromised oral home care could influence the features of erosion lesions. These diverse characteristics of erosion lesions could make identification difficult. This article describes pertinent signs of erosion defects associated with the regular and diet varieties of acidic beverages and discusses their causative factors. This information is designed to avert an improper diagnosis that would derail any restorative intervention and alter a proper preventive management course. PMID- 22782047 TI - Implementation of an international short-term dental mission. AB - Dental professionals serve across the globe, working to alleviate the pain and suffering caused by dental disease. Many dental professionals serve on international mission trips, yet little has been published in the professional literature to guide dentists in establishing and operating a volunteer dental clinic in an international mission setting on a short-term basis. This article reports on multiple aspects of planning a short-term dental mission trip, including considerations in the selection of an indigenous national partner, concerns regarding the safety of patients and participants, scope of care decision-making, and the requisite equipment and supplies. PMID- 22782048 TI - Localized gingival enlargement. Adenomatoid odontogenic tumor. PMID- 22782049 TI - Erythematous patch of buccal mucosa. Squamous cell carcinoma. PMID- 22782050 TI - In situ remineralization of early caries by a new high-fluoride dentifrice. AB - The present study evaluated the ability of a high-fluoride dentifrice containing tricalcium phosphate to remineralize white spot lesions and inhibit lesion formation. Three demineralized enamel blocks and three healthy blocks (cut from a group of 30 molars), were exposed in pairs (one demineralized, one sound) via an appliance worn by 30 adults in a three-phase crossover study lasting 28 days per phase. The pairs were exposed to three dentifrices: one contained 5,000 ppm fluoride with tricalcium phosphate, one contained 5,000 ppm fluoride alone, and one contained no fluoride at all. Lesion status was analyzed using surface microhardness and transverse microradiography. Surface microhardness showed that the two dentifrices containing fluoride significantly inhibited enamel demineralization (p < 0.05) and significantly remineralized white spot lesions (p < 0.05), while the fluoride-free dentifrice did not. The results indicate that combining fluoride with tricalcium phosphate could provide more anti-caries benefits compared to using fluoride alone. PMID- 22782051 TI - Preorthodontic implant placement in the planned postorthodontic position: a simplified technique and clinical report. AB - Interdisciplinary cases can require orthodontic correction with implant anchorage prior to the placement of implant-supported restorations. Definitive implants for orthodontic anchorage offer several advantages compared to temporary attachment devices. Preorthodontic definitive implant placement requires accurate and detailed treatment planning to visualize the final orthodontic result and the optimal restoration position. This article describes a simplified method for creating a radiographic-surgical template for preorthodontic imaging and correct implant placement in the planned postorthodontic position. This approach uses common materials to combine the information from a preorthodontic diagnostic cast and the orthodontic setup/diagnostic wax-up/trial equilibration cast. PMID- 22782052 TI - Effectiveness of castor oil extract on Escherichia coli and its endotoxins in root canals. AB - This in vitro study sought to evaluate the effectiveness of castor oil extract used as an irrigating solution on Escherichia coli and its endotoxins in root canals. Sixty single-rooted teeth were prepared (using castor oil extract as irrigating solution) and divided into five groups (n = 12): Group 1 samples were treated with calcium hydroxide (Ca(OH)2), Group 2 samples were treated with polymyxin B, Group 3 samples were treated with Ca(OH)2 and 2% chlorhexidine gel (CHX), and Group 4 samples were treated with castor oil extract. A control group used physiological saline solution as an irrigant. Canal content samples were collected at four different times: immediately after instrumentation, seven days after instrumentation, after 14 days of intracanal medication, and seven days after removal of intracanal medication. A plating method was used to assess antimicrobial activity and the quantification of endotoxins was evaluated by the chromogenic Limulus lysate assay. Data were submitted to ANOVA and a Dunn test (a = 5%). Irrigation with castor oil extract decreased E. coli counts but had no effect on the level of endotoxins. Samples taken seven days after removal of medication revealed a significant reduction in endotoxin levels in Groups 3 and 4. Compared to the saline solution irrigation, castor oil extract decreased microorganism counts in root canals immediately after canal preparation. None of the medications used completely eliminated endotoxins in the root canal. PMID- 22782053 TI - Curing light burns. AB - This study sought to reveal the potential heat generated by a light-emitting diode (LED) curing light, which has generally been considered to be relatively cool. It is likely that similarly designed curing lights will produce a similar level of heat and have the potential to cause damage to soft tissue. PMID- 22782054 TI - In vitro shear bond strength of resin-based luting cements to dentin. AB - The aim of this study was to determine how resin cement, self-adhesive resin cement, and resin-modified glass ionomer cement affected shear bond strength to dentin. Sixty composite resin disks (3 mm in diameter x 3 mm in length) were prepared and divided into four groups (n = 15): Group 1, composite disk bonded to dentin with composite resin and a bonding agent; Group 2, composite disk bonded to dentin with a self-adhesive resin cement; Group 3, composite disk bonded to dentin with a different self-adhesive resin cement; and Group 4, composite disk bonded to dentin with a resin-modified glass ionomer cement. The composite resin was loaded into a syringe (internal diameter 3 mm), photocured in an oven, and cut into 3 mm slices with a low-speed saw. The samples were bonded to dentin per the manufacturer's instructions. All specimens were stored in distilled water (at 37 degrees C) for 24 hours. The shear bond strength test was conducted using a universal testing machine at a crosshead speed of 0.5 mm/min until failure. Conventional resin cement and a bonding agent exhibited significantly higher shear bond strength values than all other materials tested. PMID- 22782055 TI - Combined CBCT and sialogram: report of three cases. AB - Cone beam computed tomography (CBCT) has been applied to an array of clinical scenarios. Its application within the oral and maxillofacial region continues to impress those involved with its use. Salivary gland imaging has been accomplished by standard radiographs, computed tomography, and more recently, CBCT. This article reviews the application of sialograms with CBCT and discusses three patients who received this procedure during their evaluations. The importance of the oral and maxillofacial radiologist is highlighted as a fundamental part of the health care team. PMID- 22782056 TI - A longitudinal study of the survival of interproximal root caries lesions restored with glass ionomer cement via a minimally invasive approach. AB - The prevalence of gingival recessions and the number of root surfaces exposed to the oral environment both increase with age. In turn, these increases place the older population at increased risk for caries; it is estimated that 23.7% of those over the age of 65 have root caries.1 Glass ionomer (GI) seems particularly suitable for restoring root lesions, as it has good esthetic and anti-cariogenic properties, allows for chemical bonding to teeth, and has gained wide acceptance. This article describes a minimally invasive approach for restoring interproximal root caries lesions with GI; in this study, 66 such lesions were restored and followed for up to 80 months. The results show that the radiographic quality score was the single most important predictor for restoration survival. High quality restorations survived an average of 74 months (SE = 2.7), with a cumulative survival rate of 77.4% at 80 months. Age, gender, and periodontal status were unrelated to restoration survival. PMID- 22782057 TI - Influence of thickness and area of reline on the stress distribution in peri implant bone during the healing period: a three-dimensional finite element analysis. AB - The current study used finite element analysis to evaluate how the thickness of reline material and the area of its placement in conventional complete dentures affected the stress distribution in peri-implant bone during function in the healing period. For this study, three-dimensional models were created to simulate a severely resorbed mandible with two implants placed recently in the anterior region. Two of these models received a layer of soft liner material that covered the entire length of the denture base (1.5 mm or 3.0 mm); for the other sample models, soft liner material was placed (in thicknesses of 1.5 mm or 3.0 mm) in the implant region only. The models were exported to mechanical simulation software; two simulations were performed by placing a load in the mandibular right canine (35 N) and the mandibular right first molar (50 N). Data were quantitatively and qualitatively evaluated by means of maximum principal stress. In all cases, models that received 3.0 mm of soft liner material showed lower values of stress concentration than those receiving 1.5 mm of soft liner material. Likewise, localized application of soft liner in the implant region showed lower stress concentration compared with models in which the entire denture base was relined. These results indicate that the thickness and area of reline in conventional complete dentures has a direct effect on stress distribution in the peri-implant bone tissue during the healing period. PMID- 22782058 TI - Radiopacity of different shades of resin-based restorative materials compared to human and bovine teeth. AB - This study evaluated the radiopacity of different shades of resin-based restorative materials and compared the results to human and bovine dental hard tissues. Disk specimens 6 mm in diameter and 1 mm thick (N = 220, n = 10) were prepared from the following restorative materials: . eight shades of nanofilled composite (Aelite Aesthetic Enamel), . seven shades of nanohybrid composite (Grandio Universal), . six shades of photopolymerized polyacid modified compomer (Glasiosite), and . one shade of hybrid composite (X-tra fil U). Human canine dentin (n = 10), bovine enamel (n = 10), and an aluminum (Al) step wedge were used as references. The optical density values of each material were measured from radiographic images using a transmission densitometer. Al step wedge thickness and optical density values were plotted, and equivalent Al thickness (eq Al) values were determined for radiopacity measurements of each material. The data were analyzed using a non-parametric one-way ANOVA (Kruskal-Wallis), and multiple comparisons were made with a Student-Newman-Keuls post hoc test (a = 0.05). Different shades of resin-based restorative materials tested did not reveal statistically significant differences within each material group (p > 0.05). Radiopacity values of the resin-based restorative materials investigated varied depending on their types; however, within different shades of one material type, radiopacity values were comparable. Every shade of nanocomposite material other than Aelite Aesthetic Enamel Incisal LT Gray showed comparable radiopacity to human dentin. Other materials tested demonstrated higher radiopacity compared to human dentin and bovine enamel. PMID- 22782059 TI - One-visit endodontic retreatment of combined external/internal root resorption using a calcium-enriched mixture. AB - Combined external and internal root resorption (ERR/IRR) is a rare endodontic disease that leads to alteration of the root canal anatomy. This report describes the management of an endodontically failed molar that was severely affected by ERR/IRR. Radiographic examination demonstrated inadequate obturation of the root canals associated with ERR/IRR and a large periradicular lesion. During nonsurgical endodontic retreatment, the root canals were subjected to conventional chemomechanical debridement. In the same session, the entire distal root canal was obturated using a calcium-enriched mixture (CEM) cement, and the mesial canals were obturated with gutta-percha/sealer. The clinical findings and follow-up radiographs indicated favorable treatment outcomes after 12 months. One visit application of CEM cement could be a successful approach for the management of combined ERR/IRR. PMID- 22782060 TI - In vivo effect of titanium tetrafluoride and sodium monofluorophosphate dentifrice on remineralization: a preliminary split-mouth clinical trial. AB - The aim of this preliminary, split-mouth clinical trial was to evaluate how incipient carious lesions on permanent tooth enamel were affected by 4% titanium tetrafluoride (TiF4) when used with a sodium monofluorophosphate (MFP) dentifrice. Eight children were selected for this study, providing 18 pairs of permanent anterior teeth with incipient carious lesions. TiF4 was applied once to half of the sample teeth, while all teeth were brushed with the MFP dentifrice for four weeks. Clinical (texture, size, and brightness) and illustrative (photos and scanning electronic microscope replica) evaluations were performed. Descriptive-statistical analysis of the data was performed by analyzing pairs of teeth, using statistical software. Remineralization occurred in 13 of the 18 pairs of teeth that received both forms of treatment; seven pairs were partially remineralized while six pairs showed total remineralization (McNemar test: p = 0.375). Teeth treated with both TiF4 and MFP showed a 74.5% reduction in lesion size, compared to a 67% reduction in teeth treated with the MFP dentifrice only. The results indicate that a single application of TiF4 in conjunction with toothbrushing with a fluoride-containing dentifrice was no more effective than the use of dentifrice alone for treating incipient carious lesions. PMID- 22782061 TI - Clinical evaluation of nanofill and nanohybrid composite in Class I restorations: a 12-month randomized trial. AB - This randomized trial evaluated the 12-month clinical performance of nanofill, a nanohybrid, and a microhybrid composite in restorations in occlusal cavities of posterior teeth. This study utilized 41 patients, each of whom had three molars affected by primary caries or the need to replace restorations. All restorations were performed in accordance with the manufacturer's recommendations and evaluated in accordance with U.S. Public Health Service-modified criteria. Based on the results of the present study, the material investigated demonstrated acceptable clinical performance after 12 months of clinical service. Long-term re evaluations are necessary for a more detailed analysis of these composites. PMID- 22782062 TI - Coronomaxillary space and its significance in complete denture retention--case reports. AB - The coronomaxillary space defines the distal-most extension of the maxillary denture border, and it usually is tightened during mouth opening. It has been reported that its adequate filling or overfilling is helpful in prosthesis retention. Two types of individual anatomical variations can affect the size of this space: vertical or lateral. With vertical variations, the space increases or does not vary when the mouth is opened; therefore, the prosthesis border must be thicker to obtain adequate retention. With lateral variations, the coronomaxillary space is reduced when the mouth is opened; therefore, the prosthesis border must be thin. The case reports presented here show how complete denture retention can be augmented by the careful recording of the coronomaxillary space dimensions. PMID- 22782063 TI - Surgical resection technique of a fused supernumerary lateral incisor: a clinical report and review of the literature. AB - This case report presents the surgical and restorative management of a fused supernumerary left lateral incisor. The diagnosis was confirmed using conventional radiographs and CT. The case report discusses the value of CT for evaluation of the root relationships and describes the varied morphology associated with supernumerary incisors, the surgical resection technique, partial pulpotomy, and restoration with composite resin after mechanical exposure of the remaining tooth's pulp. PMID- 22782064 TI - Esthetic rehabilitation of anterior discolored teeth with lithium disilicate all ceramic restorations. AB - The esthetic treatment of darkened anterior teeth represents a great challenge to dentists, because dental materials ideally should match the natural teeth. The optical behavior of the final restoration is determined by the color of the underlying tooth structure, the color of the luting agent, and the thickness and opacity of the ceramic material used. This article reports a case in which veneers and full crowns made of heat-pressed, lithium disilicate glass-ceramic were used for the esthetic rehabilitation of anterior discolored teeth. The patient was referred for treatment with defective anterior composite resin restorations, provisional acrylic resin crowns, darkening of the gingival margins, and uneven gingival contours. The multidisciplinary treatment plan included dental bleaching, periodontal plastic surgery to create gingival symmetry, and indirect all-ceramic restorations using high-opacity lithium disilicate glass-ceramic ingots. The treatment was successful and an excellent esthetic result was achieved. PMID- 22782066 TI - Evidence for excited state intramolecular charge transfer in benzazole-based pseudo-stilbenes. AB - Two azo compounds were obtained through the diazotization reaction of aminobenzazole derivatives and N,N-dimethylaniline using clay montmorillonite KSF as catalyst. The synthesized dyes were characterized using elemental analysis, Fourier transform infrared spectroscopy, and (13)C and (1)H NMR spectroscopy in solution. Their photophysical behavior was studied using UV-vis and steady-state fluorescence in solution. These dyes present intense absorption in the blue region. The spectral features of the azo compounds can be related to the pseudo stilbene type as well as the E isomer of the dyes. Excitation at the absorption maxima does not produce emissive species in the excited state. However, excitation around 350 nm allowed dual emission of fluorescence, from both a locally excited (LE, short wavelength) and an intramolecular charge transfer (ICT, long wavelength) state, which was corroborated by a linear relation of the fluorescence maximum (nu(max)) versus the solvent polarity function (Deltaf) from the Lippert-Mataga correlation. Evidence of TICT in these dyes was discussed from the viscosity dependence of the fluorescence intensity in the ICT emission band. Theoretical calculations were also performed in order to study the geometry and charge distribution of the dyes in their ground and excited electronic states. Using DFT methods at the theoretical levels BLYP/Aug-cc-pVDZ, for geometry optimizations and frequency calculations, and B3LYP/6-311+G(2d), for single-point energy evaluations, the calculations revealed that the least energetic and most intense photon absorption leads to a very polar excited state that relaxes non radioactively, which can be associated with photochemical isomerization. PMID- 22782065 TI - Templated chemistry for monitoring damage and repair directly in duplex DNA. AB - We report the fluorogenic detection of the product of base excision repair (an abasic site) in a specific sequence of duplex DNA. This is achieved by DNA templated chemistry, employing triple helix-forming probes that contain unnatural nucleobases designed to selectively recognize the site of a missing base. Light up signals of up to 36-fold were documented, and probes could be used to monitor enzymatic removal of a damaged base. PMID- 22782067 TI - Adherence to airway clearance therapies by adult cystic fibrosis patients. AB - BACKGROUND: Airway clearance therapy (ACT) is critical in cystic fibrosis (CF). OBJECTIVES: To determine rates of self-reported adherence to ACT by patients treated in an adult CF program, to identify patient characteristics associated with poor adherence, to typify adherence according to ACT technique, and to indicate reasons for poor adherence. METHODS: Our cross-sectional study included CF subjects age 16 years and older. Enrollees were evaluated via general structured questionnaire, adherence questionnaire, clinical assessment, spirometry, and S(pO(2)) values. Each was stratified by self-reporting protocol as high, moderate, or poor adherence to ACT. Concordance between physiotherapist recommended ACT technique and self-reported subject adherence was subjected to agreement analysis. RESULTS: Of the 63 subjects studied, 38 (60%) qualified as high adherence, 12 (19%) as moderate adherence, and 13 (21%) as poor adherence. Logistic regression identified education level (less than high school) as an independent factor associated with poor adherence (odds ratio 10.2, 95% CI 1.23 84.7, P = .03). Positive expiratory pressure (kappa = 0.87) and flutter device (kappa = 0.63) usage both corresponded with a high level of agreement, while active cycle of breathing technique (kappa = 0.40) and autogenic drainage (kappa = 0.39) each showed moderate agreement. Agreement was low for percussion and postural drainage (kappa = 0.23). Reasons given most frequently for poor adherence to ACT were "not enough time to do ACT" (28%), "cannot be bothered" (16%), and "do not enjoy ACT technique" (8%). Many (32%) provided no reason. CONCLUSIONS: Study outcomes showed a high rate of ACT adherence in adult CF subjects. Lower level of education was the most important factor in poor adherence to ACT. Self-reported adherence and treatment recommendations were in best agreement with positive expiratory pressure and flutter device techniques. PMID- 22782068 TI - The structure of cardiac glycogen in healthy mice. AB - Transmission electron micrographs of glycogen extracted from healthy mouse hearts reveal aggregate structures around 133 nm in diameter. These structures are similar to, but on average somewhat smaller than, the alpha-particles of glycogen found in mammalian liver. Like the larger liver glycogens, these new particles in cardiac tissue appear to be aggregates of beta-particles. Free beta-particles are also present in liver, and are the only type of particle seen in skeletal muscle. They have diameters from 20 to 50 nm. We discuss the number distributions of glycogen particle diameters and the implications for the structure-function relationship of glycogens in these tissues. We point out the possible implications for the study of glycogen storage diseases, and of non-insulin dependent diabetes mellitus. PMID- 22782069 TI - Antitumor and immunomodulating activity of a polysaccharide from Sophora flavescens Ait. AB - The immunostimulatory activity of Sophora flavescens polysaccharide (SFPW1) was evaluated by using in vitro cell models and in vivo animal models. The results demonstrated that SFPW1 could effectively inhibit the tumor growth in H22 tumor bearing mice and promote the splenocyte proliferation, thus resulting in a prolonged life survival. For assay in vitro, SFPW1 significantly strengthened peritoneal macrophages to devour H22 tumor cells and stimulated macrophages to produce nitric oxide (NO) via up-regulation of inducible NO synthase (iNOS) activity. However, no direct cytotoxicity against H22 tumor cells was observed in vitro. These results suggest that SFPW1 might be a strong natural immunomodulator and the antitumor effect of this polysaccharide is associated with its potent immunostimulating effect. PMID- 22782070 TI - Synthesis and characterization of carboxymethyl potato starch and its application in reactive dye printing. AB - Carboxymethyl potato starch (CMPS) was synthesized with a simple dry and multi step method as a product of the reaction of native potato starch and monochloroacetic acid in the presence of sodium hydroxide. The influence of the molar ratio of sodium hydroxide to anhydroglucose unit, the volume of 95% (v/v) ethanol, the rotation rate of motor driven stirrer and the reaction time for degree of substitution (DS) were evaluated. The product was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray diffractometry (XRD). FTIR spectrometry showed new bonds at 1618 and 1424 cm-1 when native starch underwent carboxymethylation. SEM pictures showed that the smooth surface of native starch particles was mostly ruptured. XRD revealed that starch crystallinity was reduced after carboxymethylation. The viscosity of the mixture paste of carboxymethyl starch and sodium alginate (SA) was measured using a rotational viscometer. In addition, the applied effect of mixed paste in reactive dye printing was examined by assessing the fabric stiffness, color yield and sharp edge to the printed image in comparison with SA. And the results indicated that the mixed paste could partially replace SA as thickener in reactive dye printing. The study also showed that the method was low cost and eco-friendly and the product would have an extensive application in reactive dye printing. PMID- 22782072 TI - Nuclear receptor regulation of bile acid and nutrient metabolism: 51st Annual Max Miller Lecture in Diabetes Research presented by David Mangelsdorf, PhD. PMID- 22782071 TI - Characterization of an isopentenyl diphosphate isomerase involved in the juvenile hormone pathway in Aedes aegypti. AB - Isopentenyl diphosphate isomerase (IPPI) is an enzyme involved in the synthesis of juvenile hormone (JH) in the corpora allata (CA) of insects. IPPI catalyzes the conversion of isopentenyl pyrophosphate (IPP) to dimethylallyl pyrophosphate (DMAPP); afterward IPP and DMAPP condense in a head-to-tail manner to produce geranyl diphosphate (GPP), this head-to-tail condensation can be repeated, by the further reaction of GPP with IPP, yielding the JH precursor farnesyl diphosphate. An IPPI expressed sequence tag (EST) was obtained from an Aedes aegypti corpora allata + corpora cardiaca library. Its full-length cDNA encodes a 244-aa protein that shows a high degree of similarity with type I IPPIs from other organisms, particularly for those residues that have important roles in catalysis, metal coordination and interaction with the diphosphate moiety of the IPP. Heterologous expression produced a recombinant protein that metabolized IPP into DMAPP; treatment of DMAPP with phosphoric acid produced isoprene, a volatile compound that was measured with an assay based on a solid-phase micro extraction protocol and direct analysis by gas chromatography. A. aegypti IPPI (AaIPPI) required Mg(2+) or Mn(2+) but not Zn(2+) for full activity and it was entirely inhibited by iodoacetamide. Real time PCR experiments showed that AaIPPI is highly expressed in the CA. Changes in AaIPPI mRNA levels in the CA in the pupal and adult female mosquito corresponded well with changes in JH synthesis (Li et al., 2003). This is the first molecular and functional characterization of an isopentenyl diphosphate isomerase involved in the production of juvenile hormone in the CA of an insect. PMID- 22782074 TI - Metal-directed assembly of chiral bis-Zn(II) Schiff base structures. AB - Tetra-Schiff bases derived from (chiral) bis-salphen ligand scaffolds furnish, upon metalation with appropriate metal reagents, their multinuclear structures with associated Zn(OAc)(2) or Zn(OH)(2) fragments. The tendency of retaining these salts was investigated using four different (chiral) bis-salphen scaffolds. The presence of the additional Zn ions was supported by NMR studies, mass determinations and X-ray crystallography showing in two cases the possible mode of coordination within these multinuclear structures. In one case, dimerization of the Zn(3) complex leads to a unique hexanuclear Zn(6) complex being a mixture of diastereoisomeric complexes as revealed by NMR spectroscopy. PMID- 22782073 TI - Management and adherence to VTE treatment guidelines in a national prospective cohort study in the Canadian outpatient setting. The Recovery Study. AB - Documenting patterns and outcomes of venous thromboembolism (VTE) management and degree of adherence by clinicians to treatment guidelines could help identify remediable gaps in patient care. Prospective, clinical practice-based data from Canadian outpatient settings on management of VTE, degree of adherence with treatment guidelines and frequency of recurrent VTE and bleeding during follow-up was obtained in a multicentre, prospective observational study. From 12 Canadian centres, we assessed 868 outpatients with acute symptomatic VTE who received the low-molecular-weight heparin (LMWH) enoxaparin alone or with vitamin K antagonists (VKA), at baseline and at six months (or at the end of treatment, whichever came first). Index VTE was limb deep venous thrombosis (DVT) in 583 (67.2%) patients, pulmonary embolism (PE) with or without DVT in 262 (30.2%) patients, and unusual site DVT in 23 (2.6%) patients. VTE was unprovoked in 399 (46.0%) patients, associated with cancer in 74 (8.5%) patients, transient risk factors in 327 (37.7%) patients and hormonal factors in 68 (7.8%) patients.With regard to guideline adherence, 58 (7.3%) patients received <5 days LMWH and 114 (14.5%) had overlap <1 day. Among patients with cancer-related VTE, 59.5% were prescribed LMWH monotherapy and 43.2% received such treatment for >3 months. Only 38.1% of patients with transient VTE risk factors had received thromboprophylaxis. Our study provides useful information on clinical presentation, management and related outcomes in Canadian outpatients with VTE. Our results suggest there may be important gaps in use of thromboprophylaxis to prevent VTE and use of LMWH monotherapy to treat cancer-related VTE. PMID- 22782075 TI - On the pathway of photoexcited electrons: probing photon-to-electron and photon to-phonon conversions in silicon by ATR-IR. AB - Photoexcitation and charge carrier thermalization inside semiconductor photocatalysts are two important steps in solar fuel production. Here, photoexcitation and charge carrier thermalization in a silicon wafer are for the first time probed by a novel, yet simple and user-friendly Attenuated Total Reflectance Infrared spectroscopy (ATR-IR) system. PMID- 22782076 TI - Oxidation mechanism of the intermetallic compound Ti3Al from ab initio thermodynamics. AB - Ab initio density-functional theory and thermodynamics calculations are combined to establish a microscopic mechanism for the oxidation of the alpha(2) Ti(3)Al(0001) surface. The surface energies as functions of the chemical potentials, as well as structural relaxations and electronic densities of states, are determined. The surface phase diagram (SPD) of the alpha(2)-Ti(3)Al(0001) systems with different defects and at various oxygen coverages is constructed. It is found that the Al antisite defect prefers to segregate on the alpha(2) Ti(3)Al(0001) surface and oxygen adsorption enhances the segregation with the formation of the surface with three Al antisites per unit surface cell (i.e. the top surface layer is full of Al atoms) at the initial stage of oxidation, accounting for the aluminum selective oxidation observed experimentally. After the initial stage of oxidation, the O-alpha(2)-Ti(3)Al(0001) system manifests itself with a non-uniform double-phase SPD, suggesting the competition between oxidations of the Al and Ti elements in the oxidation process. This result explains the experimentally observed second regime of oxidation in which both metal elements are oxidized. PMID- 22782078 TI - Impact of the presence of medical equipment in images on viewers' perceptions of the trustworthiness of an individual on-screen. AB - BACKGROUND: It is now common practice for doctors to consult patients by means other than face-to-face, often appearing before the patient on a computer screen. Also, many websites are using depictions of health professionals to increase the credibility of their services. Being trustworthy is an essential attribute for successful ehealth services. Little is known about which depicted accessories make a health professional appear more trustworthy. OBJECTIVE: To estimate the odds of an individual on-screen being rated trustworthy when viewed in a static image holding or wearing specific items of medical equipment. METHODS: We surveyed consecutive people attending community pharmacies to collect prescriptions in Western Australia. Respondents were presented with a series of 10 photographs, generated at random, of a man with varying numbers and combinations of medical equipment: stethoscope, reflex hammer, surgical scrubs, otoscope, and pen. They were then invited to rate the man as honest, trustworthy, honorable, moral, ethical, or genuine, or a combination of these, on the Source Credibility Scale. RESULTS: A total of 168 of 250 people gave informed consent, for a participation rate of 67.2%. There were 102 female and 66 male respondents. Of the 168 respondents, 96 (57%) were born in Australia and 102 (60.7%) were attending medical practices with more than one general practitioner. The mean age of respondents was 47 (SD 16) years (range 26-92 years). When only 1 item was present in an image, the stethoscope was associated with the highest odds for the person being considered honest (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.6-4.3), trustworthy (OR 2.3, 95% CI 1.4-3.8), honorable (OR 2.7, 95% CI 1.6 4.5), moral (OR 2.4 95% CI 1.4-4.1), ethical (OR 2.6, 95% CI 1.5-4.6), and genuine (OR 1.8, 95% CI 1.0-3.1). The presence of a stethoscope increased the odds of the person being rated in a positive light in all photographs in which it was included. CONCLUSIONS: When an individual is portrayed in a static image, concurrent presentation of 3 or more items of medical equipment, and especially a stethoscope, is likely to exert a positive influence on the viewers' perceptions of the qualities of the person depicted. PMID- 22782079 TI - N-homocysteinylation of ovine prion protein induces amyloid-like transformation. AB - Modification of protein lysyl residues by homocysteine (Hcy)-thiolactone generates proteins with altered structures and functions. It has been supposed to be one of the factors inducing protein condensation pathologies. To test a hypothesis that N-homocysteinylation may induce structural changes and in particular amyloidogenic conversion, ovine prion protein (PrP) was modified with Hcy-thiolactone and its physico-chemical properties were studied. N-Hcy-PrP formed insoluble multimers. Mass spectrometry analyses showed that at least K197 and K207 residues of PrP were the sites of N-homocysteinylation. Dynamic light scattering measurements revealed large aggregated N-Hcy-PrP particles of 1MUm diameter. They were resistant to proteinase K digestion, and enhanced thioflavin T (ThT)-binding fluorescence, what is characteristic of amyloid structures. Infrared spectroscopy measurements showed increased content of beta-sheet in N Hcy-PrP compared to unmodified PrP. Epifluorescence microscopy in the presence of ThT revealed cluster-like aggregates of N-Hcy-PrP. The collected data indicate that the N-homocysteinylation causes amyloidogenic transformation of PrP in vitro. PMID- 22782080 TI - Matrix metalloproteinase 9 regulates cell death following pilocarpine-induced seizures in the developing brain. AB - Matrix metalloproteinases (MMPs) are involved in tissue repair, cell death and morphogenesis. We investigated the role of the gelatinases MMP-2 and MMP-9 in the pathogenesis of neuronal death induced by prolonged seizures in the developing brain. Seven-day-old rats, MMP-9 knockout mice and transgenic rats overexpressing MMP-9 received intraperitoneal injections of pilocarpine, 250 mg/kg, to induce seizures. After 6-72 h pups were sacrificed, tissue from different brain regions was isolated and expression of MMP-9 mRNA and protein was analyzed by real-time PCR or Western blot. Additionally, brains were fixed and processed for TUNEL staining, immunohistochemistry and in situ zymography. We found increased numbers of TUNEL-positive cells 24 h after pilocarpine-induced seizures, most pronounced in cortical areas and the dentate gyrus, and less pronounced in thalamus. At 6-24 h, MMP-9 mRNA levels showed significant elevation compared to sham-treated controls; this effect resolved by 48 h, whereas MMP-2 mRNA levels remained stable. Cortical gelatinolytic activity, monitored by in situ zymography, was enhanced following pilocarpine-induced seizures. The MMP inhibitor GM 6001 ameliorated cell death following pilocarpine-induced seizures in infant rats. MMP 9 knockout mice were less susceptible to seizure-induced brain injury. Transgenic rats overexpressing MMP-9 were equally susceptible to seizure-induced brain injury as wild type rats. Our results suggest a significant contribution of MMP-9 to cell death after pilocarpine-induced seizures in the developing brain. As indicated by Western blot analysis, MMP-9 activation may be linked to activation of the Erk/CREB-pathway. The findings implicate involvement of MMP-9 in the pathophysiology of brain injury following seizures in the developing brain. PMID- 22782082 TI - Neurobehavioral performance in human volunteers during inhalation exposure to the unpleasant local irritant cyclohexylamine. AB - Chemosensory active volatile organic compounds occur in the breathing air at many workplaces and it has been assumed that they are potent to impair workers' cognitive performance; however, the nature of this relationship is not understood. In the current study we investigated whether the combination of strong chemosensory potency and unpleasant odor valence is a sufficient predictor for the appearance of neurobehavioral impairment. Human volunteers were exposed to three workplace-relevant concentrations of the malodorant cyclohexylamine: 0.3 (odor control condition), 0-4 (varying condition), and 10 ppm (occupational exposure limit value, OEL, Sweden & Germany). The highest exposure evoked strong chemosensory sensations (annoyance), rather much olfactory related symptoms (bad air, stink), and increase in eye-blink frequency, which can be interpreted as indicator of trigeminal mediated adversity. Neurobehavioral performance measures (reaction times, accuracy) from three visual tasks requiring attention, motor inhibition and cognitive control did not show impairment in a consistent, dose response related way and thus could not be related to cyclohexylamine exposure. Odorant characteristics of intensity and unpleasantness seem not sufficient to predict neurobehavioral impairment. Instead factors like participant selection bias, personality factors as well as effects related to the study design are discussed as contributing factors. PMID- 22782081 TI - Peri-infarct blood-brain barrier dysfunction facilitates induction of spreading depolarization associated with epileptiform discharges. AB - Recent studies showed that spreading depolarizations (SDs) occurs abundantly in patients following ischemic stroke and experimental evidence suggests that SDs recruit tissue at risk into necrosis. We hypothesized that BBB opening with consequent alterations of the extracellular electrolyte composition and extravasation of albumin facilitates generation of SDs since albumin mediates an astrocyte transcriptional response with consequent disturbance of potassium and glutamate homeostasis. Here we show extravasation of Evans blue-albumin complex into the hippocampus following cortical photothrombotic stroke in the neighboring neocortex. Using extracellular field potential recordings and exposure to serum electrolytes we observed spontaneous SDs in 80% of hippocampal slices obtained from rats 24 h after cortical photothrombosis. Hippocampal exposure to albumin for 24 h through intraventricular application together with serum electrolytes lowered the threshold for the induction of SDs in most slices irrespective of the pathway of stimulation. Exposing acute slices from naive animals to albumin led also to a reduced SD threshold. In albumin-exposed slices the onset of SDs was usually associated with larger stimulus-induced accumulation of extracellular potassium, and preceded by epileptiform activity, which was also observed during the recovery phase of SDs. Application of ifenprodil (3 MUM), an NMDA-receptor type 2 B antagonist, blocked stimulus dependent epileptiform discharges and generation of SDs in slices from animals treated with albumin in-vivo. We suggest that BBB opening facilitates the induction of peri-infarct SDs through impaired homeostasis of K+. PMID- 22782083 TI - MicroRNAs in platelet biogenesis and function. AB - Platelets are important to maintain primary haemostasis and play a key role in pathology of thrombotic and occlusive vascular disorders such as acute coronary syndrome or stroke. Despite of lacking a nucleus and genomic DNA, platelets possess diverse types of RNAs, ranging from protein coding messenger RNAs to small non-coding RNAs inherited from their parent megakaryocytes. Indeed, platelets are capable of using their own translational machinery to synthesise proteins upon their activation suggesting the possibility of post-transcriptional gene regulation in platelets. MicroRNAs (miRNAs) are highly conserved, tiny non coding RNAs exhibiting a fine-tune control of protein expression by complementary sequence recognition, binding and translational repression of protein coding mRNA transcripts. Multiple functional aspects of miRNAs as well as their expression in platelets or megakaryocytes underscore a role in platelet biology. Changes in miRNA expression patterns have been noted during platelet genesis and activation. In the present review we highlight recently identified megakaryocytic/platelet miRNAs and discuss their role in platelet biogenesis and functions essential to maintain haemostasis in the body. PMID- 22782084 TI - 8.01% CuInGaSe2 solar cells fabricated by air-stable low-cost inks. AB - CuInGaSe(2) (CIGS), a promising thin film solar cell material, has gained lots of attention in decades due to its high energy conversion efficiency and potential lower manufacture cost over conventional Si solar cells. As a cheaper processing method compared to vacuum-based techniques, solution-based deposition has been successfully applied to fabricate electronic devices, such as transistors and solar cells. In this paper, we reported CIGS thin film solar cells with an energy conversion efficiency reaching up to 8.01% using air-stable, low-cost inks. The newly developed inks consist of commercially available, low-cost compounds and solvents and can be processed using a variety of printing and coating techniques. More importantly, the inks can produce CIGS films free of copper selenides and amorphous carbon, two common by-products from solution-based CIGS processes. The mechanism for the transformation from metal salt precursor films to CIGS absorber thin films and the influence of selenium vapour pressure on absorber film quality and photovoltaic device performance were investigated and discussed. High-quality CIGS films with micrometer-sized crystals were obtained by using higher selenization partial pressure. PMID- 22782086 TI - The reaction force constant: an indicator of the synchronicity in double proton transfer reactions. AB - Earlier work, both experimental and computational, has drawn attention to the transition region in a chemical reaction, which includes the traditional transition state but extends along the intrinsic reaction coordinate xi from perturbed forms of the reactants to perturbed forms of the products. The boundaries of this region are defined by the reaction force F(xi), which is the negative gradient of the potential energy V(xi) of the system along xi. The reaction force constant kappa(xi), the second derivative of V(xi), is negative throughout the transition region. We have now demonstrated, for a series of twelve double proton transfer processes, that the profile of kappa(xi) in the transition region is an indicator of the synchronicity of the two proton migrations in each case. When they are fully or nearly fully synchronous, kappa(xi) has a single minimum in the transition region. When the migrations are considerably nonsynchronous, kappa(xi) has two minima separated by a local maximum. Such an assessment of the degree of synchronicity cannot readily be made from an examination of the transition state alone, nor it is easily detected in the profiles of V(xi) and F(xi). PMID- 22782087 TI - Nanoparticles rapidly assess specific IgE in plasma. AB - Allergy is the sixth leading cause of chronic disease in the world. This study demonstrates the feasibility of detecting allergy indicators in human plasma, noninvasively, at the point of care and with a comparable efficiency and reduced turnaround time compared with the gold standard. Peanut allergy was utilized as a model due to its widespread occurrence among the US population and fatality if not treated. The detection procedure utilized magnetic nanoparticles that were coated with an allergen layer (peanut protein extract). Peanut immunoglobulin E (IgE) was detected in concentrations close to the minimum detection range of CAP assay. The results were obtained in minutes compared with the CAP assay which requires more than 3 h. PMID- 22782088 TI - Asynchronous thoraco-abdominal motion contributes to decreased 6-minute walk test in patients with COPD. AB - BACKGROUND: Abnormal thoraco-abdominal motion may contribute to exercise limitation in patients with COPD. The current study aimed to assess how the thoraco-abdominal asynchrony in COPD patients correlates with exercise performance during the 6-minute walk test (6MWT). METHODS: Eighty-eight COPD subjects (40 moderate and 48 severe) and 14 healthy controls were evaluated at rest and during the 6MWT for the magnitude of rib cage and abdominal motion and asynchrony between the two (phase angle) with respiratory inductive plethysmography. RESULTS: Compared to healthy control subjects, subjects with COPD had similar magnitude of rib cage and abdominal motion, but greater asynchrony at rest. During the 6MWT, subjects with COPD showed decreased rib cage motion and increased asynchrony. Rib cage excursion at 3 min after the beginning of the 6MWT was an independent predictor for the 6MWT distance (P < .001), in addition to age, percent of predicted FEV(1), and residual volume/total lung capacity. There was no correlation between rib cage excursion at 3 min and St George's Respiratory Questionnaire score. CONCLUSIONS: Thoraco-abdominal asynchrony worsens early during 6MWT in subjects with moderate and severe COPD, and rib cage excursion at 3 min predicts poor walking capability. A pulmonary rehabilitation strategy devised to improve rib cage excursion may help improve exercise tolerance. PMID- 22782089 TI - Depression in high voltage power line workers. AB - OBJECTIVE: To investigate the association between effort-reward imbalance and depressive symptoms among workers in high voltage power lines. METHODS: A cross sectional study among 158 workers from an electric power company in Northeast Brazil. The main independent variables were the Effort-Reward Imbalance Model (ERI) dimensions and the main dependent variable was the prevalence of depression, as measured by the Center for Epidemiologic Studies Depression (CES D) scale. Data were analyzed by multiple logistic regression techniques. RESULTS: The group of low reward workers presented a depression prevalence rate 6.2 times greater than those in the high reward group. The depression prevalence rate was 3.3 greater in workers in the situation of imbalanced effort-reward than in those in effort-reward equilibrium. CONCLUSIONS: The prevalence of depression was strongly associated with psychosocial factors present in the work of electricity workers. PMID- 22782090 TI - GSTM1, GSTT1, and GSTP1 polymorphisms, breast cancer risk factors and mammographic density in women submitted to breast cancer screening. AB - Genetic polymorphisms in genes related to the metabolism of xenobiotics, such as genes of the glutathione S-transferases (GSTM1, GSTT1, and GSTP1) superfamily have been associated with an increased risk for breast cancer (BC). Considering the high incidence of BC in the city of Porto Alegre in southern Brazil, the purpose of this study was to characterize genotypic and allelic frequencies of polymorphisms in GSTM1, GSTT1, and GSTP1, and correlate these molecular findings with established risk factors for breast cancer including mammographic density, in a sample of 750 asymptomatic women undergoing mammographic screening. Molecular tests were performed using the multiplex polymerase chain reaction (PCR) for GSTM1 and GSTT1, and quantitative PCR for GSTP1 polymorphisms. Overall, the frequencies of GSTM1 and GSTT1 null genotypes were 45% and 21%, respectively. For GSTP1 polymorphism, genotypic frequencies were 44% for the Ile/Ile genotype, 44% for the Ile/Val genotype, and 12% for Val/Val genotype, with an allelic frequency of 66% for the wild type allele in this population, similar to results of previous international publications. There was a statistically significant association between the combined GSTM1 and GSTT1 null genotypes (M-/T-) and mammographic density in post menopausal women (p = 0.031). When the GSTT1 null (T ) genotype was analyzed isolated, the association with mammographic density in post menopausal women and in the overall sample was also statistically significant (p = 0.023 and p = 0.027, respectively). These findings suggest an association of GSTM1 and GSTT1 null genotypes with mammographic density. PMID- 22782091 TI - Added sugars: consumption and associated factors among adults and the elderly. Sao Paulo, Brazil. AB - OBJECTIVE: To investigate added sugar intake, main dietary sources and factors associated with excessive intake of added sugar. METHODS: A population-based household survey was carried out in Sao Paulo, the largest city in Brazil. Cluster sampling was performed and the study sample comprised 689 adults and 622 elderly individuals. Dietary intake was estimated based on a 24-hour food recall. Usual nutrient intake was estimated by correcting for the within-person variance of intake using the Iowa State University (ISU) method. Linear regression analysis was conducted to identify factors associated with added sugar intake. RESULTS: Average of energy intake (EI) from added sugars was 9.1% (95% CI: 8.9%; 9.4%) among adults and 8.4% (95% CI: 8.2%; 8.7%) among the elderly (p < 0.05). Average added sugar intake (% EI) was higher among women than among men (p < 0.05). Soft drink was the main source of added sugar among adults, while table sugar was the main source of added sugar among the elderly. Added sugar intake increased with age among adults. Moreover, higher socioeconomic level was associated with added sugar intake in the same group. CONCLUSIONS: Added sugar intake is higher among younger adults of higher socioeconomic level. Soft drink and table sugar accounted for more than 50% of the sugar consumed. PMID- 22782092 TI - Adverse drug reactions leading children to the emergency department. AB - The aim of the study was to determine the incidence of adverse drug reactions (ADR) that led children to hospital emergency care in a university hospital in Sao Paulo, SP. Medical charts (MC) of patients seen at the pediatric emergency department were selected according to International Classification of Diseases (ICD) codes consistent with ADR. Of 23,286 cases studied, 2,409 records were selected. An ADR was observed in 83 (0.36%) MC. Most ADR occurred in children aged 1-5 years with a slight predominance in males (51.8%). The drugs most commonly involved were antibiotics for systemic use (53.0%), vaccines (9.6%) and analgesics (7.2%). Most ADR were dermatological (54.2%) or gastrointestinal (22.9%) manifestations. Two ADR were considered severe (2.4%) while 61.4% were mild and 36.1% were moderate. The incidence was lower than in the literature, probably because it is a retrospective study that used the ICD for selecting the data assessed. The characteristics of ADR are similar to those found in other countries. Interventions are needed to improve the diagnosis and the use of antibiotics, as they were the drugs most involved in the ADR observed. Research in hospital emergency is important to acknowledge ADR that occur outside the hospital setting and may help to identify the most severe ones. Despite limitations, the method requires few resources and materials, and is a good alternative to initial diagnosis. The present study should be followed by studies with higher sensitivity to detect these reactions in order to propose prevention measures. PMID- 22782093 TI - Differentials in vital information in the state of Pernambuco, Brazil, 2006-2008. AB - OBJECTIVE: To assess differentials in official birth and death data for estimating infant mortality. METHODS: An ecological study was conducted based on data obtained from birth and death information systems in the state of Pernambuco, northeastern Brazil, between 2006 and 2008. The following indicators were used: age-standardized mortality rate, relative mean deviation of mortality rate, ratio of reported to estimated live births, relative mean deviation of birth rate and proportion of deaths of unknown cause. These indicators were grouped into three dimensions: mortality, fertility and ill-defined causes. Based on predetermined criteria, municipalities were classified as follows: consolidated vital data; vital data in the consolidation phase; and non consolidated data. The data were analyzed using EpiInfo and Terraview for map preparation. RESULTS: Of the 185 municipalities in the state of Pernambuco, 141 (76.2%) were classified as having consolidated vital data, accounting for about 85% of the state population, and 17 (9.2%) were classified as having non consolidated data, accounting for only 4.9% of the population. Larger municipalities (50,000 inhabitants or more) showed better data quality. CONCLUSION: The approach studied proved itself valuable to assess the quality of vital information and identify inequalities in Pernambuco. Reduction of inequalities is a challenge in this state in the sense of enabling vital information to be analyzed directly from data systems at the local level. It will also allow assessing the effectiveness of initiatives to reduce infant mortality in Pernambuco. PMID- 22782094 TI - Cancer in the Azores: initial results from a recently established population based cancer registry. AB - INTRODUCTION: The Azores archipelago has long been the Portuguese region that presents the highest mortality rates for certain cancers. Lack of incidence data has prevented the evaluation of the actual burden of this disease in the Azorean population. METHODS: Malignant tumours (ICD-O 5th Digit /3) initially diagnosed between the January 1st 2000 and December 31st 2002 were retrieved from the database of the recently established population-based cancer registry. Crude, age specific and age-standardized rates were calculated and confidence intervals were estimated using Poisson approximation. Relative risks of developing cancer in the Azores when compared to mainland Portugal have been represented by standardized ratios. Quality indicators, including Mortality:Incidence (M:I) ratios, were also assessed. RESULTS: Overall, the data shows a high incidence rate for some malignant diseases, specifically in men. Compared to those living in mainland Portugal, both Azorean men (RR 1.412; 99% CI 1.407-1.416) and women (1.127; 1.125 1.129) presented a significantly higher risk of developing cancer, all sites combined. When compared with other cancer registries, a less favourable cancer survival pattern is reported in the Azores, as emphasized by higher M:I ratios for several cancer sites. CONCLUSIONS: A preliminary analysis of the results suggests the presence of some major risk factors in the Azorean population, namely tobacco smoking in men. Higher M:I ratios would also point to survival disparities between the Azores archipelago and the continent, which should be further studied. PMID- 22782095 TI - Time series of visceral leishmaniasis in Aracaju, state of Sergipe, Brazil (1999 to 2008): human and canine aspects. AB - INTRODUCTION: Considered as a neglected disease by the WHO, visceral leishmaniasis (VL) has expanded and urbanized. Its transmission and expansion have been linked to several factors. OBJECTIVE: To evaluate the epidemiological aspects of VL in the city of Aracaju/SE, through retrospective studies of the historical series of human and canine VL in the 1999-2008 period. METHODS: Secondary data from SINAN (Information System for Reportable Diseases) for human cases were used. Data from canine surveys and from the Zoonosis Control Center's (ZCC) passive demand were used for canine cases. RESULTS: 192 autochthonous cases of human VL were reported, and 63.5% were male. Children aged 1-4 years were the most affected (29.2%), followed by adults aged 20-29 years (15.6%) and children aged 5-9 years (15.1%). General mortality was 8.9%, and it was higher for the 60 69 year age group (60%); 32.3% of autochthonous cases performed serology for HIV, with a 6.9% positivity. Laboratory results were confirmed mostly by indirect isolated immunofluorescence (71.1%). 58,161 dogs were serologically tested for VL, with a positivity rate of 5.4%, while 87.0% of the surveys conducted annually by the ZCC, have a 4.4%positivity rate for VL. Of the 7,501 dogs that were brought to the ZCC for multiple complaints, the serological test was positive in 12.0%. CONCLUSION: Data show the endemicity of VL in the city, revealing the need for actions to reduce the risk of the population, mostly for the group with higher incidence and mortality, such as improvement in the diagnosis of VL and its HIV-associated infection, along with monitoring of the dog population, among others. PMID- 22782096 TI - Mortality rate in children caused by traffic accidents according to geographical regions - Brazil, 1997 - 2005. AB - Fatal injuries in children caused by motor vehicle accidents represent a common situation in many countries worldwide. The present study addresses the mortality rate in children as vehicle passengers in Brazil, from 1997 to 2005. To evaluate mortality rates, the number of deaths was collected from the National Mortality Information System (SIM) and the population size was obtained using the Brazilian Bureau Census (IBGE) data available at DATASUS. Mortality rates were estimated in three-year periods and analyzed according to age groups (younger than 1 year old, 1-4 years old, 5-9 years old) and geographical regions using a 95% confidence interval. Overall results showed mortality rates of 5.68, 7.32 and 6.78 (per 1,000,000) for the 1997-1999, 2000-2002 and 2003-2005 periods, respectively for the whole country. Children younger than 1 year old had a mortality rate of 10.18 (per 1,000,000), which was higher than for the other age groups. For the period analyzed, the highest rates were observed for the Mid-West and South regions of Brazil, with rates of 13.88 and 11.47 (per 1,000,000), respectively. These results show the risk of fatal injury in children caused by motor vehicle accidents and may contribute to the establishment of educational campaigns aiming injury prevention in children as vehicle passengers. PMID- 22782097 TI - Hepatitis B vaccination and associated factors among dentists. AB - OBJECTIVE: We calculated the prevalence and studied the factors associated with hepatitis B vaccination. Reasons for non-vaccination among dentists were investigated. METHODS: A cross-sectional study was performed in Montes Claros, Minas Gerais, from 2007 to 2008, to assess hepatitis B vaccination among practicing dental surgeons. Variables were evaluated using a previously tested structured questionnaire. Data underwent descriptive analysis. Non-conditional logistic regression was used to determine the variables associated with hepatitis B vaccination (p < 0.05). RESULTS: There were 333 subjects eligible for the study, 297 (89.2%) participated, and 283 answered the question about vaccination; of these, 258 (91.2%) completed the three-dose schedule vaccination and 25 (8.8%) were not vaccinated or did not complete the vaccination schedule. Lack of information (48%) was stated as the main reason for not being vaccinated. Variables associated with vaccination were: tobacco use (OR = 2.50; IC95% = 1.22 7.13), alcohol consumption (OR = 2.99; IC95% = 1.16-7.74), satisfaction with the profession (OR = 4.62; IC95% = 1.50-8.25) and knowledge on the post-exposure management protocol (OR = 4.28; IC95% = 1.63-9.26). CONCLUSIONS: We found a high prevalence of complete vaccination among dentists in Montes Claros. It is higher among professionals who do not use tobacco and alcohol, are more satisfied with their profession and know the protocol after occupational exposure. The study suggests that the lack of information is the main reason for not being vaccinated. PMID- 22782098 TI - Food items in the food intake of children aged seven to ten years. AB - OBJECTIVE: To describe the most representative food items regarding the total intake of energy, carbohydrates, proteins and lipids in children with ages between 7 and 10 years. METHODS: A list was prepared with all food intake and quantities, and the diet composition in relation to energy and macronutrients was calculated. The list was based on information provided by a 3-day-Food Diary completed by 85 schoolchildren ranging from seven to ten years old and enrolled in a public school in Sao Paulo, Brazil. After dividing the food into 129 items, we calculated the percentage in which each item contributed to diet nutrient intake and identified those which contributed to up to 95% of the total intake of calories and selected nutrients. RESULTS: The items "White rice, Greek rice, rice with vegetables" and "Brown, black and white beans, lentils" contributed significantly to the total intake of energy and carbohydrates. The item "Whole milk, powdered milk" had a significant participation in the total intake of lipids, protein and energy. We emphasize the importance of carbohydrates and energy intake from sugar-sweetened beverages (sodas and processed juices) in the total diet intake of the children. CONCLUSIONS: the contribution of rice in the total food intake of energy and carbohydrates; of beans in energy, carbohydrates and proteins; of milk and meat in energy, protein and lipids; and bread in energy and carbohydrates is noticeable. The participation of sugar-sweetened beverage in the total intake in energy and carbohydrates and of candies in the total intake of lipids is also evident. PMID- 22782099 TI - Factors associated with dyslipidemia in children and adolescents enrolled in public schools of Salvador, Bahia. AB - OBJECTIVE: We assessed the factors associated with dyslipidemia in children and adolescents enrolled in the public school system of the city of Salvador, Bahia. METHODS: All participants were submitted to anthropometric evaluation and to cholesterol and triglyceride blood tests. Data related to food intake, physical activity and family socioeconomic and housing conditions were obtained from parents or guardians. Data were analyzed using multivariate logistic regression. RESULTS: The prevalence of dyslipidemia was 25.5% (IC:95% 22.7; 28.3). We observed a significant positive association between dyslipidemia and the following factors: overweight (OR = 3.40, 95% CI 2.07 to 5.58), moderate and high intake of risk food (OR = 1.49, 95%: 1.01 to 2.19), low and moderate intake of protective foods (OR = 1.54, 95% CI 1.05 to 2.26) and lower maternal level of schooling (OR = 1.72, 95%: 1.05 to 2.26). CONCLUSION: Overweight, inadequate food intake and low maternal level of schooling were factors associated with dyslipidemia. PMID- 22782100 TI - [Prevalence of depression and associated factors in a low income community of Porto Alegre, Rio Grande do Sul]. AB - OBJECTIVE: To estimate the prevalence and demographic and socioeconomic factors associated with depression in adults and in the elderly in a low income community of Porto Alegre, Rio Grande do Sul. METHODS: Cross-sectional study of adults with >= 20 years of age living in the Health Districts of Restinga/Extremo Sul, Porto Alegre, Rio Grande do Sul, between July and December 2009. The dependent variable was depression measured by the Edinburgh Postnatal Depression Scale. Independent variables were sex, age, current marital status, educational level and economic level. The Chi-square test was used for the crude analysis and Poisson regression with robust variance for the adjusted analysis. RESULTS: Among respondents, the prevalence of depression was 16.1% (95% CI: 14.9%, 17.4%). After adjusted analysis, we found that depression was associated with the female gender (PR = 2.38). In addition, there was a trend of higher occurrence of depression with increasing age and decreasing levels of schooling and income. CONCLUSIONS: The values of the results for depression were similar to other population studies. Specific attention should be given to women and individuals with low schooling. PMID- 22782101 TI - [Interobserver reliability of the international classification of primary care at a primary health care unit]. AB - We evaluated the International Classification of Primary Care interobserver reliability for coding the complaints reported at a primary public health unit. The study sample consisted of 300 appointments. Reasons for appointment were registered by physicians on the medical record and coding was performed by two investigators. Reliability among the classifiers as to the number of coded reasons was calculated by weighted kappa. Crude kappa coefficients were used for the remaining analyses (chapter codes and full codes). A total of 634 reasons were coded by the first classifier and 699 by the second one. Crude reliability of numbers of reasons was moderate, with a 0.71 weighted kappa (95% Confidence Interval [95%CI]: 0.68-0.73). Regarding chapter codes and full codes, reliability was substantial (kappa = 0.89; 95%CI: 0.87-0.91) and moderate (kappa = 0.72; 95% CI: 0.68-0.76), respectively. Our results suggest a good performance of the Classification for coding reasons for visit in primary care, even when data are obtained from physician consultation notes. PMID- 22782102 TI - [Sociodemographic factors associated with different domains of physical activity in adults of black ethnicity]. AB - OBJECTIVE: To analyze the prevalence and sociodemographic factors associated with different domains of physical activity among adults of black ethnicity. METHODS: Cross-sectional study with a sample of 2,305 black individuals from 20-96 years of age, 902 (39.1%) of which men living in the city of Salvador, Bahia, Brazil. Sociodemographic variables analyzed were: gender, age, schooling, socioeconomic status (SES), marital status, racial discrimination at work/school (RDWE), in public (RDPUP) and private (RDPRP) places and perception of police (PPN) /violence in the neighborhood (PVN), as well as total physical activity (TPA) in its different domains: leisure time (LTPA), work (WPA), commuting (CPA) and household activity (HPA). Associations were analyzed using chi-square tests, chi square trend and prevalence ratio (PR). We also used logistic regression analysis to estimate the odds ratio (OR) with a 95%confidence interval. RESULTS: The proportions of active individuals were 39.1% for TPA, 11.2% for LTPA, 9.6% for WPA, 23.7% for CPA and 33.7% for HPA. TPA was positively associated with higher schooling and inversely associated with male gender, age over 60 years and with no PPN. LTPA was positively associated with male gender, higher schooling and higher SES. WPA was inversely associated with age over 60 years and positively associated with male gender, higher schooling and no PPN. CPA was inversely associated with age over 60 years and positively associated with male gender. HPA was inversely associated with male gender, age over 60 years and no PPN and positively associated with higher schooling and SES. CONCLUSION: Socio demographic factors, particularly gender, age and schooling were associated with different domains of physical activity among adults of black ethnicity. PMID- 22782103 TI - [Smoking and alcohol consumption among university students: prevalence and associated factors]. AB - The study aimed to estimate the prevalence of smoking and alcohol intake among university students from the Federal University of Pelotas, Brazil (UFPel), as well as to investigate factors associated with both habits. The sample included 485 students who were admitted to the university in 2008. Students were sampled randomly across all schools of the UFPel campus, and answered a pre-tested questionnaire, which was administered in the classroom by a member of the research team. Of the individuals interviewed, 53.9% were females and 42.3% were under 20 years. Regarding alcohol intake, 75% used alcohol once a month or less frequently, and the prevalence of risk for abusive alcohol intake was 6.2%. Regarding smoking, 10.2% reported smoking regularly or on weekends. More than 90% of those who smoked or used alcohol started before entering the university. Smoking was directly related to age and inversely related to self-rated health. In terms of alcohol intake, those who lived with friends were more likely to use it. Our data suggest the need for implementing strategies to promote healthy lifestyles among university students. However, the fact that more than 90% of individuals started to smoke or drink before entering the university suggests that interventions should target adolescents as a whole, and not only those who are university students, because onset of smoking and alcohol intake seems to occur at earlier ages. PMID- 22782104 TI - [Continuous-use medication and associated factors in the elderly living in Quixada, Ceara, Brazil]. AB - OBJECTIVE: To analyze polypharmacy (daily use of two or more) of continuous use medication and its associated factors in the elderly. METHODS: A cross sectional study conducted with elderly individuals living in an urban area of the municipality of Quixada, Ceara, Brazil from May to December, 2009. The sample consisted of 384 individuals who were 60 years old or older and users of continuous medication. The variables studied were sociodemographic, economical, and health characteristics related to use of medications. For the analysis of the association between the dependent variable polypharmacy of continuous-use medication and the independent variables a logistic regression model was developed. RESULTS: Results showed a predominance of females, between 60 and 69 years old, married, with incomplete elementary school education, non-paid job, family income of one minimum salary, living in their own home and together with up to three individuals. A prevalence of 70.6% of polypharmacy in the elderly was found, and it was higher in women (66.4%). Factors positively associated with the use of two or more continuous-use medication were: family income over one minimum salary (OR 2.83; CI95% = 1.54-5.32); two or more self-reported chronic conditions (OR 17.71; CI95% = 9.80-31.990) and self-perception of regular to poor quality of life (OR 2.85; CI95% = 1.60-5.07). CONCLUSIONS: The study observed a practice of polypharmacy of continuous-use medications in the elderly with family income over one minimum wage, two or more chronic conditions and self-perception of regular to poor quality of life. Such status leads to questions on social, cultural, economic and health aspects. PMID- 22782105 TI - [Epidemiological profile of maternal deaths in Rio Grande do Sul, Brazil: 2004 2007]. AB - This study analyzed the epidemiological profile of maternal deaths that occurred from 2004 to 2007 in Rio Grande do Sul, by means of Maternal Mortality Rates and Specific Maternal Mortality Ratio. Data was obtained from the Health Information System database and 323 maternal deaths were identified. In order to analyze indicators, Poisson regression and statistical tests were carried out. A decrease in maternal mortality rates (0.98) was identified, although there was no difference in estimate measures (CI95% 0.87-1.10). Maternal deaths were more frequent in women who were over 40 years old, had low schooling, black skin and no partners. The period of highest risk of maternal death was during pregnancy and birth, and the main direct causes were arterial hypertension and bleeding. Maternal mortality is an important issue to be confronted and reduced, given most maternal deaths could have been avoided. PMID- 22782106 TI - [Epidemiology of powdered glass-coated kite line injuries: victims admitted to a trauma hospital in Belo Horizonte, Brazil]. AB - OBJECTIVE: To describe the characteristics of victims of powdered glass-coated (manja) kite line injuries admitted to a trauma hospital in Belo Horizonte, Brazil. METHODS: Cross-sectional study of victims with powdered glass-coated kite line injuries between 2005 and 2009. Data were obtained retrospectively from medical records. Central tendency and comparison of ratios were used to characterize victims. RESULTS: 211 victims were admitted between 2005 and 2009, 94% of which males. The majority of cases occurred in June and July (37% e 41.7%, respectively). Mean age was 15 years, with no difference between men and women. For the group of victims as a whole, upper limbs were the most prevalent site of injury, although neck and face injuries were the main site of injury among motorcyclists and cyclists. Two deaths (0.95%) were identified, both in motorcyclists, due to injury to neck structures. Residences were concentrated in three administrative areas (East, Northeast and South-central). CONCLUSION: Although the majority of injuries recorded were not severe, fatal injuries can occur, mainly among motorcyclists. Educational and preventive measures are needed to avoid potentially fatal injuries. PMID- 22782107 TI - [Social relations and self- rated health: the ageing and health project]. AB - OBJECTIVE: To investigate the association between social relationships and self perceived health in the elderly. METHODS: cross-sectional study of a representative sample of elderly individuals covered by the Family Health Program and residents in an area of high health vulnerability in Belo Horizonte, MG. Information was obtained through structured interviews. Factors associated with poor or very poor self-perceived health were identified by multiple logistic regression analysis. RESULTS: 363 out of 371 eligible elderly participated; 17.1% of elderly self-perceived their health as poor. There was a positive dose response relationship between poor self-perceived health and the number of chronic diseases and the degree of difficulty to perform daily life activities. Elderly individuals who perceived their personal relationships as bad and who could not count on anyone if they became bedridden were more likely to self-rate their health as poor. Working was negatively associated with self-perceived poor health. CONCLUSION: The results confirm the multidimensional structure of self perceived health including the issues related to health and social relationships. Our results strengthen the role of social relations on health. PMID- 22782108 TI - [Prevalence of musculoskeletal disorders in nursing professionals]. AB - A cross-sectional study estimated the prevalence of work-related musculoskeletal disorders among nursing assistants in Salvador, Bahia. Three hundred and eight workers, randomly selected, answered a questionnaire applied by trained interviewers during working hours. The majority of respondents worked the day shift and did not usually work overtime. About 34% reported having another regular job. Average time in the formal or informal labor market was 19 years. There was high occupational exposure to repetitive hand movements, standing posture, walking, inadequate postures of the trunk and manual handling of loads. The prevalence of work-related musculoskeletal disorders in at least one body segment was 83.4%.The most affected body segments were: low back (53.9%), legs (51.9%), neck (36.4%), upper back (35.7%) and shoulders (33.8%). There was high prevalence of work-related musculoskeletal disorders in the studied population, which points out to the need for improvements in the working conditions of those professionals. PMID- 22782110 TI - The role of the cilium in normal and abnormal cell cycles: emphasis on renal cystic pathologies. AB - The primary cilium protrudes from the cell surface and acts as a sensor for chemical and mechanical growth cues, with receptors for a number of growth factors (PDGFalpha, Hedgehog, Wnt, Notch) concentrated within the ciliary membrane. In normal tissues, the cilium assembles after cells exit mitosis and is resorbed as part of cell cycle re-entry. Although regulation of the cilium by cell cycle transitions has been appreciated for over 100 years, only recently have data emerged to indicate the cilium also exerts influence on the cell cycle. The resorption/protrusion cycle, regulated by proteins including Aurora-A, VHL, and GSK-3beta, influences cell responsiveness to growth cues involving cilia linked receptors; further, resorption liberates the ciliary basal body to differentiate into the centrosome, which performs discrete functions in S-, G2-, and M-phase. Besides these roles, the cilium provides a positional cue that regulates polarity of cell division, and thus directs cells towards fates of differentiation versus proliferation. In this review, we summarize the specific mechanisms mediating the cilia-cell cycle dialog. We then emphasize the examples of polycystic kidney disease (PKD), nephronopthisis (NPHP), and VHL-linked renal cysts as cases in which defects of ciliary function influence disease pathology, and may also condition response to treatment. PMID- 22782112 TI - A matricellular protein and EGF-like repeat signalling in the social amoebozoan Dictyostelium discoideum. AB - Matricellular proteins interact with the extracellular matrix (ECM) and modulate cellular processes by binding to cell surface receptors and initiating intracellular signal transduction. Their association with the ECM and the ability of some members of this protein family to regulate cell motility have opened up new avenues of research to investigate their functions in normal and diseased cells. In this review, we summarize the research on CyrA, an ECM calmodulin binding protein in Dictyostelium. CyrA is proteolytically cleaved into smaller EGF-like (EGFL) repeat containing cleavage products during development. The first EGFL repeat of CyrA binds to the cell surface and activates a novel signalling pathway that modulates cell motility in this model organism. The similarity of CyrA to the most well-characterized matricellular proteins in mammals allows it to be designated as the first matricellular protein identified in Dictyostelium. PMID- 22782111 TI - Monoamine oxidases in development. AB - Monoamine oxidases (MAOs) are flavoproteins of the outer mitochondrial membrane that catalyze the oxidative deamination of biogenic and xenobiotic amines. In mammals there are two isoforms (MAO-A and MAO-B) that can be distinguished on the basis of their substrate specificity and their sensitivity towards specific inhibitors. Both isoforms are expressed in most tissues, but their expression in the central nervous system and their ability to metabolize monoaminergic neurotransmitters have focused MAO research on the functionality of the mature brain. MAO activities have been related to neurodegenerative diseases as well as to neurological and psychiatric disorders. More recently evidence has been accumulating indicating that MAO isoforms are expressed not only in adult mammals, but also before birth, and that defective MAO expression induces developmental abnormalities in particular of the brain. This review is aimed at summarizing and critically evaluating the new findings on the developmental functions of MAO isoforms during embryogenesis. PMID- 22782115 TI - SATB1-mediated functional packaging of chromatin into loops. AB - Mammalian genomes are organized into multiple layers of higher-order chromatin structure, and in this organization chromatin looping is a striking and crucial feature that brings together distal genomic loci into close spatial proximity. Such three-dimensional organization of chromatin has been suggested to be functionally important in gene regulation. Many important questions need to be addressed, such as what types of nuclear proteins are responsible for folding chromatin into loops, whether there are any genomic marks that serve as the core sites of chromatin folding events, how distal genomic sites are brought together, and what are the biological consequences for interactions between distal genomic loci. In order to address these fundamental questions, it is essential to devise and employ methods that can capture higher-order structures formed by specific nuclear proteins at high resolution. In this article, in order to describe methods of analyzing protein-mediated chromatin interactions, we will use as an example a global genome-organizer protein, SATB1, which mediates chromatin looping. PMID- 22782116 TI - Comparison of a 4.5 F semi-rigid ureteroscope with a 7.5 F rigid ureteroscope in the treatment of ureteral stones in preschool-age children. AB - The aim of this study was to compare the success and complication rates of a 4.5 F ureteroscope with a 7.5 F ureteroscope in the treatment of urolithiasis in preschool-age children. We retrospectively reviewed 69 ureteroscopy (URS) procedures in a pediatric population (40 boys, 29 girls). We divided the patients into two groups according to the type of ureteroscope used: group 1 (n = 42, Storz 7.5 F) and group 2 (n = 27, Wolf 4.5 F). We statistically compared all the procedures performed in both groups regarding patient age, complication rates, whether the procedure was therapeutic, and whether we used a guidewire. Additionally, in cases with ureteral stones, we also compared the stone clearance rate and the necessity of X-ray imaging between the two groups. The mean patient age was 56.04 months in group 1 and 47.48 months in group 2 (p = 0.057). The stone-free rate was 78.6 % in group 1 and 92.6 % in group 2 (p > 0.05). However, when we compared the stone-free rates for patients younger than 3 years, the rate was 66.7 % in group 1 and 93.8 % in group 2 (p < 0.05). The difference was not statistically significant for patients between the ages of 4 and 7 years. The success and failure rates revealed better outcomes for treatment of ureteral stones with a 4.5 F ureteroscope. We recommend the use of the mini-ureteroscope, especially in infants and preschool-age children. PMID- 22782117 TI - Hepatic haematoma after shockwave lithotripsy for renal stones. AB - Extracorporeal shock wave lithotripsy (SWL) is a non-invasive procedure for urolithiasis. Only a very small portion of patients suffer from post-SWL haematoma and most of them have perinephric haematoma formation. We present two patients who developed subcapsular hepatic haematomas after SWL, followed by a review of the literature on the condition. PMID- 22782118 TI - Microstructural analysis of a urinary stone as evidence of experimentally observed processes of their formation. PMID- 22782119 TI - Theoretical prediction of impurity effects on the internally oxidized metal/oxide interface: the case study of S on Cu/Al2O3. AB - A detrimental sulfur effect on adhesion is known for iron- and nickel-oxide interfaces, but has never been reported on copper-oxide interfaces. Here we present a first-principles based study on the effects of temperature, interfacial stoichiometry, Al activity, and S segregation on the internally oxidized Cu/alpha Al(2)O(3) interface. The calculated "interfacial phase diagram" for temperatures of interest suggests that the equilibrium interface structure is near the transition between Al-rich and stoichiometric phases. The Al-rich type interface is significantly stronger than the stoichiometric counterpart. The S effect on the Cu/alpha-Al(2)O(3) interface is obvious: S strongly segregates to both types of interface, degrades the adhesion (by ~65%) and also reduces the size stability of alumina particles in Cu. PMID- 22782113 TI - Regulation of intestinal epithelial permeability by tight junctions. AB - The gastrointestinal epithelium forms the boundary between the body and external environment. It effectively provides a selective permeable barrier that limits the permeation of luminal noxious molecules, such as pathogens, toxins, and antigens, while allowing the appropriate absorption of nutrients and water. This selective permeable barrier is achieved by intercellular tight junction (TJ) structures, which regulate paracellular permeability. Disruption of the intestinal TJ barrier, followed by permeation of luminal noxious molecules, induces a perturbation of the mucosal immune system and inflammation, and can act as a trigger for the development of intestinal and systemic diseases. In this context, much effort has been taken to understand the roles of extracellular factors, including cytokines, pathogens, and food factors, for the regulation of the intestinal TJ barrier. Here, I discuss the regulation of the intestinal TJ barrier together with its implications for the pathogenesis of diseases. PMID- 22782120 TI - Body centered cubic magnesium niobium hydride with facile room temperature absorption and four weight percent reversible capacity. AB - We have synthesized a new metastable metal hydride with promising hydrogen storage properties. Body centered cubic (bcc) magnesium niobium hydride (Mg(0.75)Nb(0.25))H(2) possesses 4.5 wt% hydrogen gravimetric density, with 4 wt% being reversible. Volumetric hydrogen absorption measurements yield an enthalpy of hydride formation of -53 kJ mol(-1) H(2), which indicates a significant thermodynamic destabilization relative to the baseline -77 kJ mol(-1) H(2) for rutile MgH(2). The hydrogenation cycling kinetics are remarkable. At room temperature and 1 bar hydrogen it takes 30 minutes to absorb a 1.5 MUm thick film at sorption cycle 1, and 1 minute at cycle 5. Reversible desorption is achieved in about 60 minutes at 175 degrees C. Using ab initio calculations we have examined the thermodynamic stability of metallic alloys with hexagonal close packed (hcp) versus bcc crystal structure. Moreover we have analyzed the formation energies of the alloy hydrides that are bcc, rutile or fluorite. PMID- 22782121 TI - Molecular epidemiology of Chikungunya virus: mutation in E1 gene region. AB - Chikungunya virus is a mosquito-transmitted RNA virus and emerging as a pathogen that has a major public health impact because of the high morbidity including high fever, headache, rash, nausea, vomiting, myalgia, arthralgia with or without neurological manifestation or fulminant hepatitis. One hundred fifty-one patient samples were analyzed during the years 2006-2008, and compared conventional tests and CCRT-PCR (cell culture RT PCR). The conventional tests included ELISA, inoculation into C6/36 cell line and CPE were examined by PCR after RNA extraction. A total of 20/151 (13.2%), 8/151 (5.29%) and 7/151 (4.6%) samples were found to be positive by ELISA, cell culture and PCR, respectively. While 7/20 (35%) of the samples were positive by CCRT_PCR when ELISA 20 positive samples were detected. A total of 5/7 positive strains were sequenced in the E1 gene region. Remarkable changes (M269V, D284E, P294L, S295F, A316V, V322A, and C328W) were observed in the membrane fusion glycoprotein E1. These unique molecular features of the isolates with the continuing epidemic demonstrated high evolutionary potential and thereby indicating higher virulence. PMID- 22782123 TI - [Youth and reproduction: demograhic, behavioral and reproductive profiles in the PNDS-2006]. AB - OBJECTIVE: Analyze the sociodemographic characteristics and the sexual and reproductive behavior of young women. METHODS: A cross-sectional nationally representative study was performed about sexual, contraceptive and reproductive behavior with 2,991 women age 15 to 20 years in the National Survey on Demography and Health of Women and Children, 2006. The women were classified into three groups: sexual initiation and pregnancy before the age of 20 (group A); sexual initiation but no pregnancy before the age of 20 (group B) and no sexual initiation (group C). Women until age 25 years were included in the study about reasons for becoming pregnant and the implications for their lives. Statistical analysis considered survey weights and the complex sample design. The association between two categorical variables was assessed by chi-square test. The behavior variables were assessed using a global linear model. RESULTS: Women in group A were mainly black, poorer and with lower education level. These women had an early sexual initiation, less safe contraceptive behavior and less knowledge of reproduction physiology in comparison with group B; young women in group C were characterized by greater attendance at school and 1/3 of this group claimed to maintain their virginity until marriage. For women up to the age of 25, pregnancy before 20 years was perceived as having more positive than negative impacts upon their love life, spousal relationships, social lives and self-esteem. CONCLUSIONS: There is a significant association between pregnancy before the age of 20 and higher poverty and lower educational level. In the absence of better living conditions and opportunities, pregnancy, although unplanned, becomes "a plan for life", and is not seen as a lack of life planning. PMID- 22782122 TI - Noninvasive positive pressure ventilation for acute respiratory failure in delirious patients: understudied, underreported, or underappreciated? A systematic review and meta-analysis. AB - BACKGROUND: We performed a systematic review and meta-analysis of the literature to determine the prevalence of delirium in patients receiving noninvasive positive pressure ventilation (NPPV) for acute respiratory failure and to quantify the prognostic impact of delirium with respect to NPPV failure. METHOD: We searched the databases EMBASE (1996 to present), MEDLINE (1996 to present), PsycINFO((r)) (2002 to present) and CINAHL (1992 to present). A GoogleTM search and hand searching of bibliographies or relevant articles were also performed. We searched for prospective observational studies conducted in a setting where patients with acute respiratory failure receiving NPPV were screened for delirium. All authors independently assessed references for inclusion and extracted data. Information was collated regarding study design, baseline characteristics of included patients, and the prevalence of delirium. Where prognostic information regarding NPPV failure was reported, a risk ratio for the association between delirium and NPPV failure was derived. These values were pooled in the meta-analysis. RESULTS: Three articles were retrieved by the search strategy. These included 239 patients receiving noninvasive ventilation who were assessed for delirium. The prevalence of delirium was recorded at between 33 and 38 % with a pooled prevalence of 37 %. Two studies reported prognostic data and the risk ratios for noninvasive ventilation failure in delirium were calculated as 1.79 (95 % CI 1.09-2.94) and 3.28 (95 % CI 1.60-6.73). A meta-analysis was performed and the pooled risk ratio was found to be 2.12 (95 % CI 1.41-3.18). CONCLUSIONS: The data in this context was scarce and of low quality. A diagnosis of delirium was made in 9 patients and inferred in 80. Despite the current lack of high-quality data and studies, the high reported prevalence of delirium and the association with noninvasive ventilation failure lends support for more awareness amongst health-care professionals and more routine screening. More focused primary research is necessary in this area. Adherence to NICE guidelines regarding delirium in these patients should be a standard of care. PMID- 22782124 TI - Short Assessment of Health Literacy for Portuguese-speaking Adults. AB - OBJECTIVE: To develop and validate a short health literacy assessment tool for Portuguese-speaking adults. METHODS: The Short Assessment of Health Literacy for Portuguese-speaking Adults is an assessment tool which consists of 50 items that assess an individual's ability to correctly pronounce and understand common medical terms. We evaluated the instrument's psychometric properties in a convenience sample of 226 Brazilian older adults. Construct validity was assessed by correlating the tool scores with years of schooling, self-reported literacy, and global cognitive functioning. Discrimination validity was assessed by testing the tool's accuracy in detecting inadequate health literacy, defined as failure to fully understand standard medical prescriptions. RESULTS: Moderate to high correlations were found in the assessment of construct validity (Spearman's coefficients ranging from 0.63 to 0.76). The instrument showed adequate internal consistency (Cronbach's alpha=0.93) and adequate test-retest reliability (intraclass correlation coefficient=0.95). The area under the receiver operating characteristic curve for detection of inadequate health literacy was 0.82. A version consisting of 18 items was tested and showed similar psychometric properties. CONCLUSIONS: The instrument developed showed good validity and reliability in a sample of Brazilian older adults. It can be used in research and clinical settings for screening inadequate health literacy. PMID- 22782125 TI - [Outcomes of planned home birth assisted by nurses, from 2005 to 2009, in Florianopolis, Brazil]. AB - A cross-sectional study was performed to analyze obstetric and neonatal results of planned home births assisted by obstetric nurses in the city of Florianopolis, Southern Brazil. Data collected from the medical records of 100 parturient women cared for between 2005 and 2009 indicated 11 hospital transfers, nine of which underwent a Cesarean section. The majority of women who had a home birth showed normal fetal heart beat (94.0%) and progress on the partogram (61.0%), vertical water delivery was the position most frequently chosen (71.9%), newborns had an Apgar score >= 7 at five minutes (98.9%), episiotomy was performed in 1.0%, and 49.4% did not need perineal suturing. Outcomes indicated that planned home birth is safe. PMID- 22782126 TI - [Nutritional therapy in metabolic changes in individuals with HIV/AIDS]. AB - OBJECTIVE: To analyze the effect of nutritional treatment on metabolic changes caused by the use of antiretroviral therapy in adults with HIV/AIDS. METHODS: A systematic review of literature was conducted in the PubMed, Lilacs and Cochrane databases, between 1996 and 2010, including crossover and randomized controlled clinical trials performed in adults with HIV/AIDS using antiretroviral therapy and without opportunistic diseases. The intervention of interest was oral nutritional supplementation and/or a change in lifestyle due to specific dietary treatment: dyslipidemia, insulin resistance, lipodystrophy and systemic arterial hypertension. The Jadad scale was used for a qualitative classification of articles. RESULTS: A total of 385 articles were found, of which seven were included. The interventions used in these studies were as follows: diet, diet and physical exercises, diet and supplementation, and only supplementation. Dyslipidemia was the outcome assessed in all studies. Studies that assessed omega 3 supplementation found a significant reduction in triglycerides. The specific diet with omega-3 supplementation showed an increase in HDL-cholesterol. Chrome nicotinate supplementation did not have an effect on dyslipidemia. Changing one's lifestyle, including diet and physical activity, significantly reduced waist circumference, lipodystrophy and systolic blood pressure. CONCLUSIONS: Reduction in tryglicerides with omega-3 supplementation was the nutritional intervention with the strongest scientific evidence. Prescribing a specific diet appeared to be the most adequate intervention to increase HDL-cholesterol. Inferences could not be made about the nutritional treatment of total cholesterol, LDL-cholesterol and insulin resistance. Changes in lifestyle can promote an improvement in lipodystrophy and blood pressure. PMID- 22782127 TI - [Classical public health thinking in Sao Paulo during the era of health centers and health education]. AB - The article reviews the ideas and concepts of health service organization that followed the introduction of the Health Center model by the Health Service reform in 1925. It discusses the thinking of Geraldo de Paula Souza, Rodolfo Mascarenhas and Reinaldo Ramos, distinguished representatives of "classical thought" of public health in Sao Paulo, Southeastern Brazil. PMID- 22782128 TI - Roll-to-roll printed resistive WORM memory on a flexible substrate. AB - The fabrication process and the operation characteristics of a fully roll-to-roll printed resistive write-once-read-many memory on a flexible substrate are presented. The low-voltage (<10 V) write operation of the memories from a high resistivity '0' state to a low resistivity '1' state is based on the rapid electrical sintering of bits containing silver nanoparticles. The bit ink is formulated by mixing two commercially available silver nanoparticle inks in order to tune the initial square resistance of the bits and to create a self-organized network of percolating paths. The electrical performance of the memories, including read and write characteristics, is described and the long-term stability of the less stable '0' state is studied in different environmental conditions. The memories can find use in low-cost mass printing applications. PMID- 22782129 TI - [Opioid guidelines: yesterday and today: current guideline recommendations for chronic non-tumor pain]. AB - Guidelines on opioid therapy for patients with chronic non-tumor pain should support pain relief, prevent iatrogenic suffering, collateral health damage and legal restrictions on the availability of opioid analgesics. A total of six North American and two European committees recently developed guidelines which differ from the previous ones by being based on many more randomized controlled trials. In anticipation of lower analgesic effects than are to be expected from solely consensus-based guidelines, they recommended a more thorough control of individual therapeutic opioid trials than before. Drafting recommendations for a preferably individual efficacy prognosis is a further objective of the guidelines. This article will discuss if previous and current recommendations of opioid guidelines meet these requirements. PMID- 22782130 TI - [Stress lesions in the upper gastrointestinal tract]. AB - Clinically relevant bleeding in the upper gastrointestinal tract due to stress lesions is a rare event; however, the related mortality may be as high as 13% (van Leerdam, Best Pract Res Clin Gastroenterol 2008; 22:209-224). Most often affected are patients in the intensive care unit (ICU) with impaired perfusion as the protective pathways are critically dependent on a near normal blood flow. Minimal mucosal lesions with a tiny hemorrhage can escalate to severe bleeding as the coagulation potential in the presence of an acidic pH is clearly decreased. Mechanical ventilation and coagulopathy are recognized risk factors and these patients should receive an acid suppressing therapy. Proton pump inhibitors (PPI) and histamine type 2 receptor antagonists (H(2)RA) are equal in their ability to prevent stress-related bleeding. However, the side effects of PPI can cause severe morbidity and therefore H(2)RAs may be the drug of choice for prophylaxis. Endoscopy is recommended as a diagnostic and therapeutic tool for patients with active bleeding. Treatment with PPI in this scenario (before and after endoscopy) may reduce complications by leading to premature hemostasis and reduced recurrence of bleeding. PMID- 22782133 TI - Exploring new 129Xe chemical shift ranges in HXeY compounds: hydrogen more relativistic than xenon. AB - Among rare gases, xenon features an unusually broad nuclear magnetic resonance (NMR) chemical shift range in its compounds and as a non-bonded Xe atom introduced into different environments. In this work we show that (129)Xe NMR chemical shifts in the recently prepared, matrix-isolated xenon compounds appear in new, so far unexplored (129)Xe chemical shift ranges. State-of-the-art theoretical predictions of NMR chemical shifts in compounds of general formula HXeY (Y = H, F, Cl, Br, I, -CN, -NC, -CCH, -CCCCH, -CCCN, -CCXeH, -OXeH, -OH, SH) as well as in the recently prepared ClXeCN and ClXeNC species are reported. The bonding situation of Xe in the studied compounds is rather different from the previously characterized cases as Xe appears in the electronic state corresponding to a situation with a low formal oxidation state, between I and II in these compounds. Accordingly, the predicted (129)Xe chemical shifts occur in new NMR ranges for this nucleus: ca. 500-1000 ppm (wrt Xe gas) for HXeY species and ca. 1100-1600 ppm for ClXeCN and ClXeNC. These new ranges fall between those corresponding to the weakly-bonded Xe(0) atom in guest-host systems (delta < 300 ppm) and in the hitherto characterized Xe molecules (delta > 2000 ppm). The importance of relativistic effects is discussed. Relativistic effects only slightly modulate the (129)Xe chemical shift that is obtained already at the nonrelativistic CCSD(T) level. In contrast, spin-orbit-induced shielding effects on the (1)H chemical shifts of the H1 atom directly bonded to the Xe center largely overwhelm the nonrelativistic deshielding effects. This leads to an overall negative (1)H chemical shift in the range between -5 and -25 ppm (wrt CH(4)). Thus, the relativistic effects induced by the heavy Xe atom appear considerably more important for the chemical shift of the neighbouring, light hydrogen atom than that of the Xe nucleus itself. The predicted NMR parameters facilitate an unambiguous experimental identification of these novel compounds. PMID- 22782131 TI - Recording human electrocorticographic (ECoG) signals for neuroscientific research and real-time functional cortical mapping. AB - Neuroimaging studies of human cognitive, sensory, and motor processes are usually based on noninvasive techniques such as electroencephalography (EEG), magnetoencephalography or functional magnetic-resonance imaging. These techniques have either inherently low temporal or low spatial resolution, and suffer from low signal-to-noise ratio and/or poor high-frequency sensitivity. Thus, they are suboptimal for exploring the short-lived spatio-temporal dynamics of many of the underlying brain processes. In contrast, the invasive technique of electrocorticography (ECoG) provides brain signals that have an exceptionally high signal-to-noise ratio, less susceptibility to artifacts than EEG, and a high spatial and temporal resolution (i.e., <1 cm/<1 millisecond, respectively). ECoG involves measurement of electrical brain signals using electrodes that are implanted subdurally on the surface of the brain. Recent studies have shown that ECoG amplitudes in certain frequency bands carry substantial information about task-related activity, such as motor execution and planning, auditory processing and visual-spatial attention. Most of this information is captured in the high gamma range (around 70-110 Hz). Thus, gamma activity has been proposed as a robust and general indicator of local cortical function. ECoG can also reveal functional connectivity and resolve finer task-related spatial-temporal dynamics, thereby advancing our understanding of large-scale cortical processes. It has especially proven useful for advancing brain-computer interfacing (BCI) technology for decoding a user's intentions to enhance or improve communication and control. Nevertheless, human ECoG data are often hard to obtain because of the risks and limitations of the invasive procedures involved, and the need to record within the constraints of clinical settings. Still, clinical monitoring to localize epileptic foci offers a unique and valuable opportunity to collect human ECoG data. We describe our methods for collecting recording ECoG, and demonstrate how to use these signals for important real-time applications such as clinical mapping and brain-computer interfacing. Our example uses the BCI2000 software platform and the SIGFRIED method, an application for real-time mapping of brain functions. This procedure yields information that clinicians can subsequently use to guide the complex and laborious process of functional mapping by electrical stimulation. PREREQUISITES AND PLANNING: Patients with drug-resistant partial epilepsy may be candidates for resective surgery of an epileptic focus to minimize the frequency of seizures. Prior to resection, the patients undergo monitoring using subdural electrodes for two purposes: first, to localize the epileptic focus, and second, to identify nearby critical brain areas (i.e., eloquent cortex) where resection could result in long-term functional deficits. To implant electrodes, a craniotomy is performed to open the skull. Then, electrode grids and/or strips are placed on the cortex, usually beneath the dura. A typical grid has a set of 8 x 8 platinum-iridium electrodes of 4 mm diameter (2.3 mm exposed surface) embedded in silicon with an inter-electrode distance of 1cm. A strip typically contains 4 or 6 such electrodes in a single line. The locations for these grids/strips are planned by a team of neurologists and neurosurgeons, and are based on previous EEG monitoring, on a structural MRI of the patient's brain, and on relevant factors of the patient's history. Continuous recording over a period of 5-12 days serves to localize epileptic foci, and electrical stimulation via the implanted electrodes allows clinicians to map eloquent cortex. At the end of the monitoring period, explantation of the electrodes and therapeutic resection are performed together in one procedure. In addition to its primary clinical purpose, invasive monitoring also provides a unique opportunity to acquire human ECoG data for neuroscientific research. The decision to include a prospective patient in the research is based on the planned location of their electrodes, on the patient's performance scores on neuropsychological assessments, and on their informed consent, which is predicated on their understanding that participation in research is optional and is not related to their treatment. As with all research involving human subjects, the research protocol must be approved by the hospital's institutional review board. The decision to perform individual experimental tasks is made day-by-day, and is contingent on the patient's endurance and willingness to participate. Some or all of the experiments may be prevented by problems with the clinical state of the patient, such as post-operative facial swelling, temporary aphasia, frequent seizures, post-ictal fatigue and confusion, and more general pain or discomfort. At the Epilepsy Monitoring Unit at Albany Medical Center in Albany, New York, clinical monitoring is implemented around the clock using a 192-channel Nihon Kohden Neurofax monitoring system. Research recordings are made in collaboration with the Wadsworth Center of the New York State Department of Health in Albany. Signals from the ECoG electrodes are fed simultaneously to the research and the clinical systems via splitter connectors. To ensure that the clinical and research systems do not interfere with each other, the two systems typically use separate grounds. In fact, an epidural strip of electrodes is sometimes implanted to provide a ground for the clinical system. Whether research or clinical recording system, the grounding electrode is chosen to be distant from the predicted epileptic focus and from cortical areas of interest for the research. Our research system consists of eight synchronized 16-channel g.USBamp amplifier/digitizer units (g.tec, Graz, Austria). These were chosen because they are safety-rated and FDA-approved for invasive recordings, they have a very low noise-floor in the high-frequency range in which the signals of interest are found, and they come with an SDK that allows them to be integrated with custom written research software. In order to capture the high-gamma signal accurately, we acquire signals at 1200Hz sampling rate-considerably higher than that of the typical EEG experiment or that of many clinical monitoring systems. A built-in low-pass filter automatically prevents aliasing of signals higher than the digitizer can capture. The patient's eye gaze is tracked using a monitor with a built-in Tobii T-60 eye-tracking system (Tobii Tech., Stockholm, Sweden). Additional accessories such as joystick, bluetooth Wiimote (Nintendo Co.), data glove (5(th) Dimension Technologies), keyboard, microphone, headphones, or video camera are connected depending on the requirements of the particular experiment. Data collection, stimulus presentation, synchronization with the different input/output accessories, and real-time analysis and visualization are accomplished using our BCI2000 software. BCI2000 is a freely available general purpose software system for real-time biosignal data acquisition, processing and feedback. It includes an array of pre-built modules that can be flexibly configured for many different purposes, and that can be extended by researchers' own code in C++, MATLAB or Python. BCI2000 consists of four modules that communicate with each other via a network-capable protocol: a Source module that handles the acquisition of brain signals from one of 19 different hardware systems from different manufacturers; a Signal Processing module that extracts relevant ECoG features and translates them into output signals; an Application module that delivers stimuli and feedback to the subject; and the Operator module that provides a graphical interface to the investigator. A number of different experiments may be conducted with any given patient. The priority of experiments will be determined by the location of the particular patient's electrodes. However, we usually begin our experimentation using the SIGFRIED (SIGnal modeling For Realtime Identification and Event Detection) mapping method, which detects and displays significant task-related activity in real time. The resulting functional map allows us to further tailor subsequent experimental protocols and may also prove as a useful starting point for traditional mapping by electrocortical stimulation (ECS). Although ECS mapping remains the gold standard for predicting the clinical outcome of resection, the process of ECS mapping is time consuming and also has other problems, such as after-discharges or seizures. Thus, a passive functional mapping technique may prove valuable in providing an initial estimate of the locus of eloquent cortex, which may then be confirmed and refined by ECS. The results from our passive SIGFRIED mapping technique have been shown to exhibit substantial concurrence with the results derived using ECS mapping. The protocol described in this paper establishes a general methodology for gathering human ECoG data, before proceeding to illustrate how experiments can be initiated using the BCI2000 software platform. Finally, as a specific example, we describe how to perform passive functional mapping using the BCI2000 based SIGFRIED system. PMID- 22782134 TI - "Common synthetic scaffolds" in the synthesis of structurally diverse natural products. AB - Selected natural products have long been considered as desirable targets for total synthesis due to their unique biological properties and their challenging structural complexity. Laboratory synthesis of natural compounds usually relies on target-oriented synthesis, involving the production, isolation and purification of successive intermediates, requiring multiple steps to arrive to the final product. A far more economical approach using common synthetic scaffolds that can be readily transformed through biomimetic-like pathways to a range of structurally diverse natural products has been evolved in the last decade, leading synthesis to new directions. This tutorial review critically presents the hallmarks in this field. PMID- 22782135 TI - The ex vivo reversibility of dabigatran-induced whole-blood coagulopathy as monitored by thromboelastography: mechanistic implications for clinical medicine. PMID- 22782136 TI - Detection of cucumber mosaic virus isolates from banana by one-step reverse transcription loop-mediated isothermal amplification. AB - Cucumber mosaic virus (CMV) is one of the most devastating threats to the banana industry. A single-tube, one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the rapid detection of CMV infected banana and plantain (Musa spp.). The reaction was performed in a single tube at 63 degrees C for 90 min using a real-time turbidimeter, with an improved closed-tube visual detection system in which fluorescent dye was added to the inside of the lid prior to amplification. This RT-LAMP assay is an alternative method for the rapid detection of CMV in banana plants and tissue culture materials. PMID- 22782137 TI - Experimental infection of laboratory-bred bank voles (Myodes glareolus) with murid herpesvirus 4. AB - MuHV-4 is a natural pathogen of rodents of the genus Apodemus (e.g., wood mice, yellow-necked mice) and Myodes glareolus (bank voles). We report experimental MuHV-4 infection of bank voles in comparison with infection of A. sylvaticus (wood mice) and BALB/c mice. Like in wood mice, the level of productive replication in the lungs of bank voles was significantly lower than in BALB/c mice. In contrast to other hosts, however, the level of latent infection in the lung and spleen of bank voles was extremely low. These findings, together with those of previous studies, suggest that bank voles are an occasional and inefficient host for MuHV-4. PMID- 22782138 TI - Establishment and maintenance of persistent infection by picobirnavirus in greater rhea (Rhea Americana). AB - A study aimed to determine the infection model that picobirnavirus (PBV) established in birds was conducted in a farm of greater rheas in Cordoba, Argentina. Analysis of stools collected during a longitudinal study involving seven birds provided evidence that PBV is acquired very early in life and establishes a persistent infection in the host, which is characterized by intermingled periods of high, low and silent viral activity. Genomic analysis indicated that the rheas excreted virus with nucleotide sequence identity between 90.5-100 % and that more than one PBV strain with different electropherotype profiles could be involve in the infection. This report provides the first evidence of persistent infection of PBV in birds. The natural history of PBV infection has begun to be understood, and it appears that asymptomatic PBV infected mammals and birds could persistently excrete the virus in stool samples, contributing to wide circulation of the virus in the environment. PMID- 22782140 TI - Synthesis, properties and applications of nanoscale nitrides, borides and carbides. AB - Nanoscale nitrides, borides and carbides are a fascinating type of materials, which have aroused tremendous and continuous research interest for decades owing to their special mechanical, electrical, optical, photoelectronic, catalytic properties and widespread uses. In this feature article, recent developments and breakthroughs in the synthesis, properties and applications of nanometre scale nitrides (BN, Si(3)N(4), GaN, noble nitrides), borides (LnB(6), LnB(2), Fe(3)BO(5), LiMBO(3)) and carbides (carbon, SiC, TiC, NbC, WC) were briefly reviewed in sequence of their different dimensions (1D, 2D and 3D). In particular, our latest advances in the "autoclave route" fabrication of nanoscale nitrides, borides, and carbides were highlighted. The challenges, issues and perspectives of the synthetic methodologies and potential applications concerning the above-mentioned materials were also briefly discussed. PMID- 22782139 TI - Respiratory therapy organizational changes are associated with increased respiratory care utilization. AB - BACKGROUND: The effect of the respiratory therapist (RT)/patient ratio and RT organizational factors on respiratory resource utilization is unknown. We describe the impact of a multi-component intervention that called for an increase in RT/patient ratio (1:14 to 1:10), improved RT orientation, and formation of a core staffing model on best practice, including spontaneous breathing trials (SBTs) and catheter and bronchoscopically directed lower respiratory tract cultures, or bronchoalveolar lavage (BAL), in both ventilated and non-ventilated patients in the ICU. METHODS: We conducted a single center, quasi-experimental study comparing 651 patients with single and first admissions between April 19, 2005 and April 18, 2006 before the RT services reorganization with 1,073 patients with single and first admissions between September 16, 2007 and September 4, 2008. Baseline characteristics were compared, along with SBTs, BAL use, lower respiratory tract cultures, and chest physiotherapy. RESULTS: Patients in the 2 groups were similar in terms of age (52.9 +/- 15.8 y vs 53.9 +/- 16.4 y, P = .23), comorbidity as measured by Charlson score (2.8 +/- 2.6 vs 2.8 +/- 2.7, P = .56), and acuity of illness as measured by the Case Mix Index (3.2 +/- 3.9 vs 3.3 +/- 4.1, P = .47). Mechanically ventilated patients had similar prevalences of respiratory diseases (24.2% vs 25.1%, P = .61). There was an increase in SBTs (0.5% vs 73.1%, P < .001), chest physiotherapy (7.4% vs 21.6%, P < .001), BALs (24.0% vs 41.4%, P < .001), and lower respiratory tract cultures (21.5% vs 38.0%, P < .001) in mechanically ventilated patients post-intervention. CONCLUSIONS: A multi-component intervention, including an increase in RT/patient ratio, improved RT orientation, and establishment of a core staffing model, was associated with increased respiratory resource utilization and evidence-based practice, specifically BALs and SBTs. PMID- 22782141 TI - Glutamine treatment decreases plasma and lymph cytotoxicity during sepsis in rats. AB - Glutamine (Gln) is considered as a conditionally essential amino acid. Pharmacological supplementation of Gln helps to maintain the intestinal mucosal barrier, modulate cytokine production, and prevent organ injury during sepsis. Our previous study demonstrated the different effects of Gln on macrophage cytokine production in vitro or in vivo. The purpose of this study was to investigate the potential mechanism of Gln treatment to protect cells and modulate inflammation during sepsis in vivo. The results showed that administration of Gln significantly attenuated plasma-induced macrophage cytokine production and endothelial cell necrosis after cecal ligation and puncture in rats. In addition, it preserved human umbilical vein endothelial cell (HUVEC) viability and migration ability. Gln treatment also reduced lymph cytotoxicity by restoring macrophage tumor necrosis factor-alpha production, maintaining HUVEC viability, and decreasing endothelial cell necrosis. Mesenteric lymph duct ligation did not alleviate plasma cytotoxicity. Plasma lipopolysaccharide and d lactate levels were suppressed after Gln treatment. Taken together, these results indicated that Gln administration can protect cells by attenuating the cytotoxicity of plasma and mesenteric lymph during sepsis. PMID- 22782142 TI - IGF-1 alleviates ox-LDL-induced inflammation via reducing HMGB1 release in HAECs. AB - Atherosclerosis, a multifactorial chronic inflammatory response, is closely associated with oxidatively modified low-density lipoprotein (ox-LDL). High mobility group box 1 (HMGB1) is a DNA-binding protein, which upon release from cells exhibits potent inflammatory action. Insulin-like growth factor 1 (IGF-1) can elicit a repertoire of cellular responses including proliferation and anti apoptosis. However, the role of IGF-1 in inflammation is still unclear. In the present study, we aimed to investigate the role of IGF-1 in inflammation and the underlying mechanism. Human aortic endothelial cells were stimulated by ox-LDL (50 MUg/ml) to induce inflammation. The expression of intercellular adhesion molecule 1 (ICAM-1) was assessed by western blot analysis and immunofluorescence. The release of HMGB1 was determined by enzyme-linked immunosorbent assay. IGF-1 receptor (IGF-1R) expression was assessed by reverse transcription-polymerase chain reaction and western blot analysis. IGF-1R phosphorylation was determined by western blot analysis. Ox-LDL stimulation reduced IGF-1R mRNA and protein expression but increased HMGB1 release. IGF-1 treatment decreased ox-LDL-induced ICAM-1 expression potentially through reducing HMGB1 release, while picropodophyllin, an IGF-1R specific inhibitor, increased the inflammatory response. In conclusion, IGF-1 can alleviate ox-LDL-induced inflammation by reducing HMGB1 release, suggesting an unexpected beneficial role of IGF-1 in inflammatory disease. PMID- 22782143 TI - Structure-based mutant stability predictions on proteins of unknown structure. AB - The ability to rapidly and accurately predict the effects of mutations on the physicochemical properties of proteins holds tremendous importance in the rational design of modified proteins for various types of industrial, environmental or pharmaceutical applications, as well as in elucidating the genetic background of complex diseases. In many cases, the absence of an experimentally resolved structure represents a major obstacle, since most currently available predictive software crucially depend on it. We investigate here the relevance of combining coarse-grained structure-based stability predictions with a simple comparative modeling procedure. Strikingly, our results show that the use of average to high quality structural models leads to virtually no loss in predictive power compared to the use of experimental structures. Even in the case of low quality models, the decrease in performance is quite limited and this combined approach remains markedly superior to other methods based exclusively on the analysis of sequence features. PMID- 22782144 TI - Development and validation of the response to sexual difficulties scale. AB - Leading models of sexual dysfunction, such as those proposed by Masters and Johnson (1970), Barlow (1986), and Janssen, Everaerd, Spiering, and Janssen (2000), emphasize the role of anxiety and self-monitoring in the development and persistence of sexual difficulties. These models have considerable explanatory power, but focus on the intrapersonal factors that yield anxiety and self monitoring. Accounting for the interpersonal context in which sexual activity occurs is also likely to be important. For example, anxiety and self-monitoring may arise from negative, yet accurate, predictions about how one's partner will respond to one's own sexual functioning difficulties. The current studies describe the development and validation of the Response to Sexual Difficulties Scale (RSDS), which was designed to assess how one expects one's partner to respond to one's own sexual difficulties (RSDS-Own Difficulties) and how one expects oneself to respond to one's partner's sexual difficulties (RSDS-Partner Difficulties). Study 1 established the initial reliability and construct validity of the RSDS-Own Difficulties in a sample of adults in committed relationships (N = 59). Study 2 further examined the construct and discriminant validity of the RSDS Own Difficulties and Partner Difficulties in a sample of heterosexual couples (N = 87). Results indicated that both measures had strong internal consistency and were not redundant with measures of mood or personality. Scores on the RSDS-Own Difficulties and Partner Difficulties were strongly associated, indicating that reports of one's own response to one's partner's difficulty matched the partner's assessment of the reaction. RSDS scores predicted sexual functioning, relationship satisfaction, sexual satisfaction, and sexual communication. The RSDS may, then, provide a useful means of assessing the role of interpersonal factors in the development and persistence of sexual difficulties. PMID- 22782145 TI - Libman-Sacks endocarditis in pediatric patient with systemic lupus erythematosus. AB - A 16 year old female patient with systemic lupus erythematosus presented to rheumatology clinic with a new I-II/VI honking-quality mitral regurgitation murmur. The patient was initially evaluated by transthoracic echocardiogram that revealed mitral valve regurgitation and a large band of tissue under the mitral valve leaflets. Blood cultures were obtained and were negative. Transesophageal echocardiogram provided better visualization of the lesion and showed the band of tissue involving most of the chordae of the posterior mitral leaflet. A diagnosis of Libman-Sacks endocarditis was made given the aseptic nature of the lesions and the patient's underlying lupus. Aggressive management of the lupus showed reduction of the mitral regurgitation and the size of the lesion. Libman-Sacks endocarditis is best evaluated by transesophageal echocardiogram. PMID- 22782146 TI - Flash-powered transilllumination: old concept, new technology. PMID- 22782150 TI - Subcutaneous interferon alfa for the treatment of cutaneous pseudolymphoma. PMID- 22782151 TI - Geometric staged excision for the treatment of lentigo maligna and lentigo maligna melanoma: a long-term experience with literature review. AB - OBJECTIVE: To ascertain and clarify the effectiveness and advantages of the geometric staged excision technique for the removal of lentigo maligna (LM) and lentigo maligna melanoma (LMM). DESIGN: This was a retrospective review of a patient database composed of 293 cases of LM and LMM. SETTING: The Laser and Dermatologic Surgery Center in St Louis, Missouri, an academic-affiliated, private dermatologic surgery center. PATIENTS: All patients with a diagnosis of LM and LMM treated by staged excision from 1999 to 2007. MAIN OUTCOME MEASURES: The overall rate of recrudescence, margins required for clearance, stages required for clearance, and lesional characteristics were examined. RESULTS: The rate of recrudescence after geometric staged excision was 1.7% (4/239), with a mean of 32.3 months of follow-up. The mean margin to clearance after excision was 6.6 mm for LM and 8.2 mm for LMM. A total of 11.7% of LMM was initially diagnosed as LM on biopsy, with the invasive component discovered during the excision. CONCLUSIONS: Geometric staged excision is an optimal method of removal of LM and LMM given its low rate of recrudescence and ability for complete examination of the peripheral and deep margins of the specimens. PMID- 22782153 TI - Chemoprevention for keratinocytic (pre)cancers: balancing the risks and benefits. AB - QUESTION: Can celecoxib reduce the incidence of actinic keratoses (AKs) and keratinocytic cancers? DESIGN: Randomized, double-blind, placebo-controlled phase 2-3 clinical trial. SETTING: Eight centers in the United States participated and included 240 patients from January 2001 to November 2006, when the Food and Drug Administration requested termination of this trial after the worldwide withdrawal of rofecoxib. PATIENTS: The study population comprised individuals 18 years or older with Fitzpatrick skin type I to III, with 10 to 40 AKs on the upper extremities, neck, face, and scalp at baseline and a previous histological diagnosis of a keratinocytic (pre)malignant neoplasm. INTERVENTION: Celecoxib (200 mg) or placebo twice daily. MAIN OUTCOME MEASURE: The ratio of new AKs per patient at completion of the study to the number of AKs at randomization. EXPLORATORY POST HOC ANALYSIS: The mean cumulative number of keratinocytic skin cancers per patient. RESULTS: There was no difference in the incidence of AKs between the 2 groups at month 9 after randomization. The adjusted rate ratios for the celecoxib arm compared with the placebo arm were 0.41 (95% CI, 0.23-0.72) for keratinocytic skin cancers, 0.40 (95% CI, 0.18-0.93) for basal cell carcinomas (BCCs), and 0.42 (95% CI, 0.19-0.93) for squamous cell carcinomas (SCCs). CONCLUSION: Celecoxib might be effective for prevention of keratinocytic cancers but not for actinic keratoses. PMID- 22782154 TI - Unilateral facial ulceration. PMID- 22782156 TI - A 26-year-old man with an eczematous lesion on the nipple. PMID- 22782158 TI - Translucent nasal papules in a 3-year-old boy-quiz case. PMID- 22782160 TI - Lentigolike macules and erythematous plaques on trunk and extremities-quiz case. PMID- 22782163 TI - Practice gaps. The barriers and the promise of teledermatology. PMID- 22782162 TI - Why some dermatologists do not practice store-and-forward teledermatology. PMID- 22782165 TI - Ustekinumab for pyoderma gangrenosum. PMID- 22782164 TI - Autoantibody and clinical profiles in patients with discoid lupus and borderline systemic lupus. PMID- 22782167 TI - Sporty compression socks: to wear or not to wear? PMID- 22782168 TI - Acute guttate psoriasis in a 15-year-old girl with Epstein-Barr virus infection. PMID- 22782169 TI - Failure of intravenous cidofovir for generalized verrucosis in a patient with severe combined immunodeficiency. PMID- 22782170 TI - Extensive cutaneous ulcerations and necrosis associated with paroxysmal nocturnal hemoglobinuria. PMID- 22782173 TI - Beyond von Neumann--logic operations in passive crossbar arrays alongside memory operations. AB - The realization of logic operations within passive crossbar memory arrays is a promising approach to expand the fields of application of such architectures. Material implication was recently suggested as the basic function of memristive crossbar junctions, and single bipolar resistive switches (BRS) as well as complementary resistive switches (CRS) were shown to be capable of realizing this logical functionality. Based on a systematic analysis of the Boolean functions, we demonstrate here that 14 of 16 Boolean functions can be realized with a single BRS or CRS cell in at most three sequential cycles. Since the read-out step is independent of the logic operation steps, the result of the logic operation is directly stored to memory, making logic-in-memory applications feasible. PMID- 22782172 TI - Naturally occurring radionuclides in food and drinking water from a thorium-rich area. AB - This paper focuses on a survey of uranium and thorium decay chain radionuclides in food and drinking water from the thorium-rich (monazite-bearing) region of Buena, which is located in the state of Rio de Janeiro, Brazil. The radionuclide concentration values in the food and drinking water from Buena reached values higher than 100-fold the international reference values. The daily intake of radionuclides by the local population is similar to that of another high background radiation area in Brazil, but the intake is higher than that of residents from a normal background radiation area. Approximately 58 % of the food consumed by Buena inhabitants is produced locally. Based on that figure, locally produced food and the dilution of total radionuclides in the diet of residents caused by food importation are both highly relevant to a population's intake of radionuclides. The concentration values for (210)Pb and the radium isotopes in drinking water from Buena are among the highest values to be reported in the literature. (228)Ra is the most important radionuclide ingested with both food and water among the inhabitants of Buena. PMID- 22782174 TI - [The new patient rights act : the significance for surgeons]. AB - The committee draft for the new patient rights act was approved by the Federal Cabinet on 23 May 2012. Both the demands of the patient representative of the Federal government and some of the demands from the cornerstone paper of the State commission were taken into consideration.The draft of the new act contains comprehensive amendments to the Civil Code with the subtitle"Treatment contract in accordance with S630" and encompasses SS630a-h. The valid legal situation is therefore to all intents and purposes now codified. PMID- 22782175 TI - [Lateral skip metastases in papillary thyroid carcinoma]. PMID- 22782176 TI - [Selective use of transhiatal esophagectomy for esophageal cancer]. PMID- 22782177 TI - [Endoscopic transgastric necrosectomy due to infected pancreatic necrosis]. PMID- 22782178 TI - [Fiber-rich diet does not prevent diverticulosis]. PMID- 22782179 TI - [Soft tissue sarcoma : resection and plastic reconstruction]. AB - Adequate surgical removal of soft tissue sarcomas of the trunk and extremities employing safety margins of 1-2 cm is the accepted basis of multidisciplinary treatment. In cases of high risk tumors (grades G2/G3) the tumor board decision should include radiochemotherapy under study conditions. Difficult peripheral locations or perioperative complications require additional techniques, such as hyperthermic perfusion with tumor necrosis factor alpha or the complete spectrum of reconstructive plastic procedures. Patients with soft tissue sarcoma of the trunk or of the extremities should always be referred to high volume centers. PMID- 22782180 TI - Dinuclear Pt(II)-bisphosphonate complexes: a scaffold for multinuclear or different oxidation state platinum drugs. AB - Geminal bisphosphonates (BPs), used in the clinic for the treatment of hypercalcaemia and skeletal metastases, have been also exploited for promoting the specific accumulation of platinum antitumor drugs in bone tissue. In this work, the platinum dinuclear complex [{Pt(en)}(2)(MU-AHBP-H(2))](+) (1) (the carbon atom bridging the two phosphorous atoms carrying a 2-ammonioethyl and a hydroxyl group, AHBP-H(2)) has been used as scaffold for the synthesis of a Pt(II) trinuclear complex, [{Pt(en)}(3)(MU-AHBP)](+) (2), and a Pt(IV) adamantane shaped dinuclear complex featuring an oxo-bridge, [{Pt(IV)(en)Cl}(2)(MU-O)(MU AHBP-H(2))](+) (3) (X-ray structure). Compound 2 undergoes a reversible, pH dependent, rearrangement with a neat switch point around pH = 5.4. Compound 3 undergoes a one-step electrochemical reduction at E(pc) = -0.84 V affording compound 1. Such a potential is far lower than that of glutathione (-0.24 V), nevertheless compound 3 can undergo chemical reduction to 1 by GSH, most probably through a different (inner-sphere) mechanism. In vitro cytotoxicity of the new compounds, tested against murine glioma (C6) and human cervix (HeLa) and hepatoma (HepG2) cell lines, has shown that, while the Pt(IV) dimer 3 is inactive up to a concentration of 50 MUM, the two Pt(II) polynuclear compounds 1 and 2 have a cytotoxicity comparable to that of cisplatin with the trinuclear complex 2 generally more active than the dinuclear complex 1. PMID- 22782181 TI - High-throughput physical mapping of chromosomes using automated in situ hybridization. AB - Projects to obtain whole-genome sequences for 10,000 vertebrate species and for 5,000 insect and related arthropod species are expected to take place over the next 5 years. For example, the sequencing of the genomes for 15 malaria mosquitospecies is currently being done using an Illumina platform. This Anopheles species cluster includes both vectors and non-vectors of malaria. When the genome assemblies become available, researchers will have the unique opportunity to perform comparative analysis for inferring evolutionary changes relevant to vector ability. However, it has proven difficult to use next generation sequencing reads to generate high-quality de novo genome assemblies. Moreover, the existing genome assemblies for Anopheles gambiae, although obtained using the Sanger method, are gapped or fragmented. Success of comparative genomic analyses will be limited if researchers deal with numerous sequencing contigs, rather than with chromosome-based genome assemblies. Fragmented, unmapped sequences create problems for genomic analyses because: (i) unidentified gaps cause incorrect or incomplete annotation of genomic sequences; (ii) unmapped sequences lead to confusion between paralogous genes and genes from different haplotypes; and (iii) the lack of chromosome assignment and orientation of the sequencing contigs does not allow for reconstructing rearrangement phylogeny and studying chromosome evolution. Developing high-resolution physical maps for species with newly sequenced genomes is a timely and cost-effective investment that will facilitate genome annotation, evolutionary analysis, and re-sequencing of individual genomes from natural populations. Here, we present innovative approaches to chromosome preparation, fluorescent in situ hybridization (FISH), and imaging that facilitate rapid development of physical maps. Using An. gambiae as an example, we demonstrate that the development of physical chromosome maps can potentially improve genome assemblies and, thus, the quality of genomic analyses. First, we use a high-pressure method to prepare polytene chromosome spreads. This method, originally developed for Drosophila, allows the user to visualize more details on chromosomes than the regular squashing technique. Second, a fully automated, front-end system for FISH is used for high-throughput physical genome mapping. The automated slide staining system runs multiple assays simultaneously and dramatically reduces hands-on time. Third, an automatic fluorescent imaging system, which includes a motorized slide stage, automatically scans and photographs labeled chromosomes after FISH. This system is especially useful for identifying and visualizing multiple chromosomal plates on the same slide. In addition, the scanning process captures a more uniform FISH result. Overall, the automated high-throughput physical mapping protocol is more efficient than a standard manual protocol. PMID- 22782182 TI - Si nanotubes and nanospheres with two-dimensional polycrystalline walls. AB - We report on the characteristics of a new class of Si-based nanotubes and spherical nanoparticles synthesized by the dc-arc plasma method in a mixture of argon and hydrogen. These two nanostructures share common properties: they are hollow and possess very thin, highly polycrystalline and mainly oxidized walls. In particular, we get several hints indicating that their walls could constitute only one single Si oxidized layer. Moreover, we find that only the less oxidized nanotubes exhibit locally atomic ordered, snakeskin-like areas which possess a hexagonal arrangement which can be interpreted either as an sp(2) or sp(3) hybridized Si or Si-H layer. Their ability to not react with oxygen seems to suggest the presence of sp(2) configuration or the formation of silicon-hydrogen bonding. PMID- 22782183 TI - Generating prostate models by means of geometric deformation with application to computerized training of cryosurgery. AB - PURPOSE: As a part of an ongoing project to develop computerized training tools for cryosurgery, the objective of the current study is twofold: to compile literature data on the likelihood of cancer tumor growth and its effect on the prostate shape and to present a deformation scheme for a 3D organ template in order to generate clinically relevant prostate models. The long-term objective of this study is to develop a database of prostate models for computerized training. METHODS: Cryosurgery is typically performed on patients with localized prostate cancer found in stage T3 or earlier. The distribution of key geometric features likely to be found in the prostate at stage T3 is integrated into a 3D prostate template by employing the extended free-form deformation (EFFD) method. The applied scheme combines two steps: pre-selecting a set of geometric parameter values and manipulating the lattice control points until the prostate model meets the desired criteria. RESULTS: Examples for model generation are displayed, based on two 3D prostate templates previously obtained from ultrasound imaging. These examples include selected cases with unilateral and bilateral stage T3 tumor growth, suitable for incorporation into a training database. CONCLUSIONS: EFFD is an efficient method for rapid generation of prostate models. The compiled criteria for model generation do not lead to a unique shape since the contours for template deformation are randomly selected. Nevertheless, these criteria do lead to shapes resembling cancer growth, as various growth histories can lead to a tumor characterized by the same key parameter values. PMID- 22782184 TI - Free boundary morphogenesis in living matter. AB - Morphogenetic theories investigate the creation and the emergence of form in living organisms. A novel approach for studying free boundary problems during morphogenesis is proposed in this work. The presence of mass fluxes inside a biological system is coupled with the local gradient of diffusing morphogens. The contour stability of a growing material is studied using a two-dimensional system model with a rectilinear free border inside a Hele-Shaw cell. Modeling mass transport during morphogenesis allows fixing the velocity at the traveling wave solution as a function of one-dimensionless parameter. Performing a perturbation of the free boundary, the dispersion relation is derived in an implicit form. Although both the velocity of the moving front and the surface tension act as stabilizing effects at small wavelengths, the dispersion diagrams show that the rectilinear border is always unstable at large wavelengths. Further applications of this model can help give insights into a number of free boundary problems in biological systems. PMID- 22782185 TI - Thermodynamic interactions of a cis and trans benzanilide with Escherichia coli bacterial membranes. AB - The activity of a membrane interactive cis and trans benzanilide against Escherichia coli membrane mimics was investigated using Langmuir monolayers. It was found that in the presence of E. coli lipid mix monolayers, cis-benzanilide induced maximal surface pressure changes of 1 mN m(-1), whereas a reduced interaction was observed with trans-benzanilide. Compression isotherm analysis of these monolayers showed ?G(mix) < 0, indicating membrane stabilisation by both compounds. The binding coefficient for trans-benzanilide was circa 890 MUM and for the cis-benzanilide was 820 MUM, suggesting that both benzanilide compounds bound to the E. coli membranes. PMID- 22782186 TI - Hunting for a maximum highly-energetic facet that interplays with spatial charge storage for enhanced catalytic activity. AB - Exposure of highly-energetic facets challenges one's capabilities of designing new substances at the atomic level and of exploiting novel physicochemical properties. We report herein on TiO(2) microspheres with a maximum exposure of the highly-energetic facet (001). Intriguingly, these microspheres were fabricated by bundles of adjacent nanowires that grow roughly parallel along the c-axis from sphere centres to outward surfaces. In between these nanowires, there existed nanoscale boundary cavities. Reducing the nanowire diameter led to a lattice expansion, and meanwhile nanoscale boundary cavities in between nanowires were tailored to possess an optimum charge storage at a nanowire diameter of 6.2 nm. This charge storage could suppress the combination of photo-generated holes and electrons. Furthermore, owing to the lattice expansion, photo-generated holes were promoted to transfer along the c-axial to the highly-energetic facet (001) to produce reactive hydroxyl radicals. As a consequence, under UV-light irradiation, microspheres with a nanowire diameter of 6.2 nm showed a maximum photocatalytic activity among all nanowire diameters. When the microspheres were broken into segments, the catalytic activities were further enhanced and even superior to commercial P25, because of sufficient utilization of incident light. The methodology reported in this work is fundamentally important, and may offer opportunities for exploring highly-energetic facets of micro-architectures that interplay with spatial charge storage to active novel surface activities, potentially useful in various catalytic applications. PMID- 22782187 TI - Levels of prolactin in relation to coagulation factors and risk of venous thrombosis. Results of a large population-based case-control study (MEGA-study). AB - The pituitary hormone prolactin is thought to influence coagulation. We aimed to study the relation between prolactin levels, coagulation factors and risk of venous thrombosis (VT). We used data from a large population based case-control study into aetiology of first VT (MEGA-study). Prolactin levels were determined in 2,068 patients with VT and 2,785 age- and sex matched control subjects. The relation between levels of coagulation factors and prolactin was studied among the controls. In addition, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated for the risk of VT for different cut-off points of prolactin levels based on percentiles determined in the controls. Restricted analysis was performed among cases in whom blood was sampled within six months after VT. We found a rise in factor VIII and von Willebrand factor with increasing levels of prolactin in the controls. An increased risk of VT was observed when blood was sampled within six months after thrombosis (OR 2.9, 95%CI 1.1-8.1) for prolactin levels above the 99th percentile (42.6 MUg/l) relative to levels between the 20th to 80th percentile. When blood was sampled more than six months after VT no clear association could be observed (OR 1.3, 95%CI 0.7-2.3). In conclusion, we found a modest association between prolactin and symptomatic venous thromboembolism, particularly when blood was sampled close to the event. This may be explained by a causal relation or by prolactin being a marker of stress due to the thrombotic event. PMID- 22782188 TI - Synthesis of isoindoles and related iso-condensed heteroaromatic pyrroles. AB - Over the past few years, isoindoles have found wide application in materials science. Isoindole containing BODIPY dyes are highly fluorescent materials and have been extensively used in various fields of science. Phthalocyanines, metal containing cyclic tetramers of isoindole, form coordination complexes with most elements of the periodic table. These complexes are intensely coloured and are used as pigments and dyes. However, isoindoles are relatively unstable 10pi heteroaromatic systems and few synthetic methods provide these compounds in good yields. This tutorial review will give an overview of the reported synthetic methods towards isoindoles and related heteroaromatic systems over a time span of approximately 10 years (2000 to current), including the applications where they have been reported. The importance of the field will be illustrated and factors influencing product stability will be discussed. PMID- 22782190 TI - Feasibility and effectiveness of an educational program in Italian COPD patients undergoing rehabilitation. AB - BACKGROUND: Self-management education is associated with improvement in quality of life and reduction of hospital admissions. Nevertheless, the data are insufficient to formulate clear recommendations regarding the type and content of education programs for COPD patients, and few data are available on knowledge of the disease itself. OBJECTIVE: To test the level of patients' knowledge of their disease and therapy at baseline and after an educational program (COPD-EP); the feasibility of structured educational sessions; the influence of clinical status (degree of severity of disease, presence of comorbidities, oxygen use), demographics status (age, sex), previous knowledge level, previous lessons attendance and adherence of COPD-EP to the variation of knowledge after program. METHODS: Selected COPD in-patients and out-patients referred to rehabilitative hospital departments were enrolled. The study was divided into 2 parts: a pre study phase (educational materials and health team preparation) and a study phase. All COPD subjects received one educational brochure and were invited to attend seven 30-min group lessons to complete the educational program. Learning effect was evaluated by a 20-questions multiple choice learning questionnaire (LQ). RESULTS: We enrolled 158 subjects, of whom 44.9% had previous formal education lessons on COPD management and 69.6% had previous rehabilitative hospitalizations. At baseline, the LQ total score was 15.2 +/- 3.5 points, which increased to 16.9 +/- 3.0 points post COPD-EP (P < .001). Pre-to-post change of LQ scores significantly correlated with adherence (R = 0.24, P = .002) and Severity Index of Cumulative Illness Rating Scale score (R = -0.22, P = .001). Subjects with low baseline knowledge were more likely to have improved LQ scores than subjects with greater levels of knowledge. Subjects without prior educational COPD lessons improved more than subjects who had attended previous education. CONCLUSIONS: A formal COPD-EP is feasible and effective in improving subject knowledge and self-management. Specific learning instruments to follow up this population should be validated. PMID- 22782191 TI - [Quality and objectifiability of training and advanced training in urology]. AB - The attraction to study medicine has not changed, however we are facing a lack of trainees especially in surgical subspecialties like urology. Possible explanations are a 70% proportion of female students and different views on the work-life balance in the future. A high burden of theory and unrealistic multiple choice examinations support those who can learn but there are no objective and reproducible criteria to recognize the competence of a good physician early in the career. This problem continues during residency, especially in surgical subspecialities. The different medical boards in Germany responsible for the training programs have no concepts. Many attempts in other countries to objectively measure surgical skills have so far been ignored. If we do not want to lose our traditionally high competence in medicine we should join those who attempt to improve teaching and to use methods for selecting suitable candidates for surgery as soon and as objectively as possible. PMID- 22782189 TI - Connecting up and clearing out: how kinetochore attachment silences the spindle assembly checkpoint. AB - With the goal of creating two genetically identical daughter cells, cell division culminates in the equal segregation of sister chromatids. This phase of cell division is monitored by a cell cycle checkpoint known as the spindle assembly checkpoint (SAC). The SAC actively prevents chromosome segregation while one or more chromosomes, or more accurately kinetochores, remain unattached to the mitotic spindle. Such unattached kinetochores recruit SAC proteins to assemble a diffusible anaphase inhibitor. Kinetochores stop production of this inhibitor once microtubules (MTs) of the mitotic spindle are bound, but productive attachment of all kinetochores is required to satisfy the SAC, initiate anaphase, and exit from mitosis. Although mechanisms of kinetochore signaling and SAC inhibitor assembly and function have received the bulk of attention in the past two decades, recent work has focused on the principles of SAC silencing. Here, we review the mechanisms that silence SAC signaling at the kinetochore, and in particular, how attachment to spindle MTs and biorientation on the mitotic spindle may turn off inhibitor generation. Future challenges in this area are highlighted towards the goal of building a comprehensive molecular model of this process. PMID- 22782192 TI - [Medical therapy of lower urinary tract symptoms [corrected]]. AB - Male lower urinary tract symptoms (LUTS) include storage and voiding disorders and should be carefully evaluated before the start of any treatment. Medical therapy is directed at improving symptoms and reducing the risk of progression in order to improve quality of life and prevent complications, such as acute urinary retention, or the need for surgical intervention. Careful assessment of the individual complaints helps to identify the best drug which should be adapted to each individual patient's risk profile. At present, alpha(1)-adrenoreceptor inhibitors and 5-alpha reductase inhibitors and their combination form the gold standard for pharmacological treatment. In addition, anticholinergic agents are increasingly being used as monotherapy or in combination with alpha1 adrenocepetor inhibitors for patients with predominant storage disorders while phosphodiesterase 5 (PDE5) inhibitors may be suitable for patients suffering from LUTS and concomitant erectile dysfunction. PMID- 22782193 TI - [Educating transurethral electroresection of the prostate is safe and efficient: is training a risk factor for patients and hospitals?]. AB - BACKGROUND: German residents are becoming increasingly more discontent with their situation. Besides unfriendly working hours and growing bureaucracy the lack of surgical education is considered as causative. Surgical education is assumed to be time-consuming and might impair operative results. Moreover, a number of patients refuse to be misused as a teaching tool. AIM OF THE STUDY: The aim of this study was to compare operative procedures (transurethral resection of the prostate) performed by residents and consultants. PATIENTS AND METHODS: All patients underwent monopolar transurethral electroresection of the prostate for symptomatic benign enlargement. All data were collected retrospectively. Mean follow-up to collect functional results and late complications was 70 months. RESULTS: Both groups did not differ significantly in perioperative and postoperative results except for the weight of resected tissue in favor of the consultants group. Functional results and late complications were comparable in both groups. CONCLUSIONS: Transurethral resection of the prostate performed by residents is a safe and effective procedure. PMID- 22782196 TI - Feeding tubes and the prevention or healing of pressure ulcers. AB - BACKGROUND: The evidence regarding the use of feeding tubes in persons with advanced dementia to prevent or heal pressure ulcers is conflicting. Using national data, we set out to determine whether percutaneous endoscopic gastrostomy (PEG) tubes prevent or help heal pressure ulcers in nursing home (NH) residents with advanced cognitive impairment (ACI). METHODS: A propensity-matched cohort study of NH residents with ACI and recent need for assistance in eating was conducted by matching each NH resident who had a feeding tube inserted during a hospitalization to 3 without a PEG tube inserted. Using the Minimum Data Set (MDS), we examined 2 outcomes: first, whether residents without a pressure ulcer developed a stage 2 or higher pressure ulcer (n = 1124 with PEG insertion); and second, whether NH residents with a pressure ulcer (n = 461) experienced improvement of the pressure ulcer by their first posthospitalization MDS assessment (mean [SD] time between evaluations, 24.6 [32.7] days). RESULTS: Matched residents with and without a PEG insertion showed comparable sociodemographic characteristic, rates of feeding tube risk factors, and mortality. Adjusted for risk factors, hospitalized NH residents receiving a PEG tube were 2.27 times more likely to develop a new pressure ulcer (95% CI, 1.95 2.65). Conversely, those with a pressure ulcer were less likely to have the ulcer heal when they had a PEG tube inserted (OR 0.70 [95% CI, 0.55-0.89]). CONCLUSIONS: Feeding tubes are not associated with prevention or improved healing of a pressure ulcer. Rather, our findings suggest that the use of PEG tube is associated with increased risk of pressure ulcers among NH residents with ACI. PMID- 22782197 TI - Tube feeding and pressure ulcers: comment on "Feeding tubes and the prevention or healing of pressure ulcers". PMID- 22782199 TI - Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women. AB - BACKGROUND: Growing antibiotic resistance warrants studying nonantibiotic prophylaxis for recurrent urinary tract infections (UTIs). Use of lactobacilli appears to be promising. METHODS: Between January 2005 and August 2007, we randomized 252 postmenopausal women with recurrent UTIs taking part in a double blind noninferiority trial to receive 12 months of prophylaxis with trimethoprim sulfamethoxazole, 480 mg, once daily or oral capsules containing 109 colony forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 twice daily. Primary end points were the mean number of symptomatic UTIs, proportion of participants with at least 1 UTI during 12 months, time to first UTI, and development of antibiotic resistance by Escherichia coli. RESULTS: The mean number of symptomatic UTIs in the year preceding randomization was 7.0 in the trimethoprim-sulfamethoxazole group and 6.8 in the lactobacilli group. In the intention-to-treat analysis, after 12 months of prophylaxis, these numbers were 2.9 and 3.3, respectively. The between-treatment difference of 0.4 UTIs per year (95% CI, -0.4 to 1.5) was outside our noninferiority margin. At least 1 symptomatic UTI occurred in 69.3% and 79.1% of the trimethoprim-sulfamethoxazole and lactobacilli participants, respectively; median times to the first UTI were 6 and 3 months, respectively. After 1 month of trimethoprim-sulfamethoxazole prophylaxis, resistance to trimethoprim-sulfamethoxazole, trimethoprim, and amoxicillin had increased from approximately 20% to 40% to approximately 80% to 95% in E coli from the feces and urine of asymptomatic women and among E coli causing a UTI. During the 3 months after trimethoprim-sulfamethoxazole discontinuation, resistance levels gradually decreased. Resistance did not increase during lactobacilli prophylaxis. CONCLUSIONS: In postmenopausal women with recurrent UTIs, L rhamnosus GR-1 and L reuteri RC-14 do not meet the noninferiority criteria in the prevention of UTIs when compared with trimethoprim sulfamethoxazole. However, unlike trimethoprim-sulfamethoxazole, lactobacilli do not increase antibiotic resistance. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN50717094. PMID- 22782200 TI - The advantages of second best: comment on "Lactobacilli vs antibiotics to prevent urinary tract infections". PMID- 22782202 TI - Serum procalcitonin levels: comment on "Effectiveness and safety of procalcitonin guided antibiotic therapy in lower respiratory tract infections in 'real life'". PMID- 22782201 TI - Effectiveness and safety of procalcitonin-guided antibiotic therapy in lower respiratory tract infections in "real life": an international, multicenter poststudy survey (ProREAL). AB - BACKGROUND: In controlled studies, procalcitonin (PCT) has safely and effectively reduced antibiotic drug use for lower respiratory tract infections (LRTIs). However, controlled trial data may not reflect real life. METHODS: We performed an observational quality surveillance in 14 centers in Switzerland, France, and the United States. Consecutive adults with LRTI presenting to emergency departments or outpatient offices were enrolled and registered on a website, which provided a previously published PCT algorithm for antibiotic guidance. The primary end point was duration of antibiotic therapy within 30 days. RESULTS: Of 1759 patients, 86.4% had a final diagnosis of LRTI (community-acquired pneumonia, 53.7%; acute exacerbation of chronic obstructive pulmonary disease, 17.1%; and bronchitis, 14.4%). Algorithm compliance overall was 68.2%, with differences between diagnoses (bronchitis, 81.0%; AECOPD, 70.1%; and community-acquired pneumonia, 63.7%; P < .001), outpatients (86.1%) and inpatients (65.9%) (P < .001), algorithm-experienced (82.5%) and algorithm-naive (60.1%) centers (P < .001), and countries (Switzerland, 75.8%; France, 73.5%; and the United States, 33.5%; P < .001). After multivariate adjustment, antibiotic therapy duration was significantly shorter if the PCT algorithm was followed compared with when it was overruled (5.9 vs 7.4 days; difference, -1.51 days; 95% CI, -2.04 to -0.98; P < .001). No increase was noted in the risk of the combined adverse outcome end point within 30 days of follow-up when the PCT algorithm was followed regarding withholding antibiotics on hospital admission (adjusted odds ratio, 0.83; 95% CI, 0.44 to 1.55; P = .56) and regarding early cessation of antibiotics (adjusted odds ratio, 0.61; 95% CI, 0.36 to 1.04; P = .07). CONCLUSIONS: This study validates previous results from controlled trials in real-life conditions and demonstrates that following a PCT algorithm effectively reduces antibiotic use without increasing the risk of complications. Preexisting differences in antibiotic prescribing affect compliance with antibiotic stewardship efforts. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN40854211. PMID- 22782203 TI - Achieving meaningful use of health information technology: a guide for physicians to the EHR incentive programs. AB - Over 30,000 clinicians have already qualified to receive initial incentive payments for the meaningful use of electronic health records (EHRs) through the Centers for Medicare & Medicaid Services (CMS) EHR Incentive Programs. However, 2012 is the final year to receive maximum incentive payments, and many physicians still have questions regarding meaningful use objectives and how to register for, report, and attest to meaningful use. We provide herein an overview of the Medicare and Medicaid EHR Incentive Programs and guide physicians in the process of how to demonstrate meaningful use of health information technology. PMID- 22782204 TI - Health information technology comes of age: comment on "Achieving meaningful use of health information technology". PMID- 22782205 TI - The increasing burden of atrial fibrillation compared with heart failure and myocardial infarction: a 15-year study of all hospitalizations in Australia. PMID- 22782206 TI - Invited commentary-Global arrhythmia burden: the public health implications of the rise in atrial fibrillation comment on "The increasing burden of atrial fibrillation compared with heart failure and myocardial infarction". PMID- 22782207 TI - Genetic polymorphisms for estimating risk of atrial fibrillation in the general population: a prospective study. PMID- 22782208 TI - Invited commentary-Genetic prediction for common diseases. PMID- 22782209 TI - To sleep or not to sleep: do we forget our patient's sleep? PMID- 22782211 TI - Potential safety signals and their significance. PMID- 22782213 TI - Medicare coverage of intensive behavioral therapy for cardiovascular disease. PMID- 22782214 TI - The involvement of AMPA-ERK1/2-BDNF pathway in the mechanism of new antidepressant action of prokinetic meranzin hydrate. AB - It was recently discovered that ketamine can relieve depression in a matter of hours through an action on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This is much more rapid than the several weeks required for the available antidepressants to show therapeutic efficacy. However, ketamine has negative side effects. The aim of this study was to determine whether the natural prokinetic drug meranzin hydrate (MH) has a fast-acting antidepressant effect mediated by AMPA receptors. By means of in vivo and in vitro experiments, we found that (1) treatment of rats with MH at 9 mg/kg decreased immobility time in a forced swimming test (FST), as did the popular antidepressant fluoxetine and the AMPA receptor positive modulator aniracetam. Pretreatment of rats with NBQX (10 mg/kg), an antagonist of AMPA receptors, blocked this effect of MH. (2) MH increased number of crossings of forced swimming rats in the open field test. (3) FST enhanced hippocampal ERK1/2, p-ERK1/2 and BDNF expression levels. MH (9 mg/kg) treatment further up-regulated hippocampal p-ERK1/2 and BDNF expression levels, and this effect was prevented by NBQX. (4) MH-increased BDNF expression corresponded with MH-decreased immobility time in the FST. (5) In vitro experiments, we found that incubation of rats hippocampus slices with MH (10, 20 MUM respectively) increased concentrations of BDNF and p-ERK1/2. This effect of MH (20 MUM) were prevented by NBQX. In conclusion, in animals subjected to acute stress, the natural prokinetic drug MH produced a rapid effect mediated by AMPA receptors and involving BDNF modulation through the ERK1/2 pathway. PMID- 22782215 TI - Tissue transglutaminase activity protects from cutaneous melanoma metastatic dissemination: an in vivo study. AB - The role of tissue transglutaminase (TG-2, TGase-2) in cancer development is still a fascinating field of research. The available reports do not elucidate fully its mechanism of action, due to the limitations of in vitro approaches. Therefore, to understand TG-2 role in cancer, we carried out an in vivo study with a more direct approach. TG-2 was in vivo overexpressed in a murine model of melanoma (intravenous injection of B16 melanoma cells in C57BL/6N mice) by means of a plasmid carrying the TG-2 cDNA. The evaluation of the frequency and size of the metastases indicated that the number of melanoma lung foci was more markedly reduced by TG-2 overexpression than the metastatic size. Then, TG-2 overexpressing mice showed a prolonged survival with respect to control mice. Further analyses were carried by means of proteomic analysis of melanoma cell lysates and meta-analysis of published transcriptomic datasets. Proteomic analysis of cell lysates from a human melanoma cell line compared to human keratinocytes showed significant differences in the expression of TG-2 substrates known to be involved in proliferation/differentiation and cancer progression. Taken together, these findings indicate a protective role of TG-2 enzymatic activity in melanoma progression in vivo. PMID- 22782216 TI - Novel thiol- and thioether-containing amino acids: cystathionine and homocysteine families. AB - Natural L-homocysteine and L,L-cystathionine, along with a series of unnatural analogues, have been prepared from L-aspartic and L-glutamic acid. Manipulation of the protected derivatives provided omega-iodoamino acids, which were used in thioalkylation reactions of sulfur nucleophiles, such as the ester of L-cysteine and potassium thioacetate. PMID- 22782217 TI - TAT-CC fusion protein depresses the oncogenicity of BCR-ABL in vitro and in vivo through interrupting its oligomerization. AB - Chronic myeloid leukemia (CML) is a clonal hematologic malignancy characterized by the BCR-ABL protein. BCR-ABL is a constitutively active tyrosine kinase and plays a critical role in the pathogenesis of CML. Imatinib mesylate, a selective tyrosine kinase inhibitor, is effective in CML, but drug resistance and relapse occur. The coiled-coil (CC) domain located in BCR(1-72) mediates BCR-ABL tetramerization, which is essential for the activation of tyrosine kinase and transformation potential of BCR-ABL. CC domain is supposed to be a therapeutic target for CML. We purified a TAT-CC protein competively binding with the endogenous CC domain to reduce BCR-ABL kinase activity. We found that TAT-CC co located and interacted with BCR-ABL in Ba/F3-p210 and K562 cells. It induced apoptosis and inhibited proliferation in these cells. It increased the sensitivity of these cells to imatinib and reduced the phosphorylation of BCR ABL, CRKL and STAT5. We confirmed that TAT-CC could attenuate the oncogenicity of Ba/F3-p210 cells and diminish the volume of K562 solid tumor in mice. We conclude targeting the CC may provide a complementary therapy to inhibit BCR-ABL oncogenicity. PMID- 22782218 TI - Introduction: Human papillomavirus in head and neck cancer: an update for 2012 with a focus on controversial topics. AB - Human papillomavirus has emerged as a major pathogen, capable of causing cancer at many different sites. In the head and neck, human papillomavirus is associated with many squamous cell carcinomas and is particularly important in the oropharynx. This is a fast moving topic with many important epidemiological, biological, pathological, and clinical features that are often confusing and misunderstood. This article introduces a series of timely reviews and editorials on this important subject in head and neck oncology. PMID- 22782219 TI - Biology of human papillomavirus infections in head and neck carcinogenesis. AB - The association between human papillomaviruses (HPV) and oral cancer was initially suggested nearly 30 years ago by us. Today, the research interest of head and neck squamous cell carcinoma (HNSCC) has substantially increased. HPV associated HNSCC is considered a distinct clinical entity with better prognosis than the classical tobacco and alcohol associated cancers. HPV 16 seems to be the main genotype present in HNSCC and it most probably utilizes the same pathways in epithelial cell transformation as established for genital cancer. High-risk HPV E6 and E7 target the well characterized cellular proteins p53 and Rb, respectively. In addition, several other cellular targets of E6 and E7 have been identified. This review gives an overview on the biology of HPV which aids in dissecting the role of HPV in head and neck carcinogenesis. It also summarizes the possible pathways involved in creating new tools for diagnosis and therapy of HPV-associated HNSCC. PMID- 22782220 TI - Epidemiology and clinical aspects of HPV in head and neck cancers. AB - Human papillomavirus (HPV) infection is now established as a major etiologic factor for oropharyngeal cancers. Case-control studies conducted around the world show strong and consistent associations of markers of HPV exposure with risk of oropharyngeal cancers (range of odds ratios [OR] for oral oncogenic HPV infections = 3.6-230.0, ORs for HPV16 L1 antibodies = 2.3-182.0, and ORs for HPV16 E6/E7 antibodies = 9.2-231.0. HPV-positive oropharyngeal cancers are epidemiologically distinct from HPV-negative ones, and are characterized by younger age at onset, male predominance, and strong association with sexual behaviors. Importantly, HPV-positive oropharyngeal cancer patients have substantially improved outcomes (28-80 % reductions in the risk of death) than HPV-negative patients. Given the superior survival, younger age, and good performance status of HPV-positive oropharyngeal cancer patients, de-intensified therapies are currently being considered for this group of patients. Recent analyses of cancer registry data show dramatic increases in incidence of oropharyngeal cancers during the past 15-20 years in several parts of the world, highlighting the need for prevention strategies. If proven efficacious, currently available prophylactic HPV vaccines hold great promise for primary prevention of HPV-associated oropharyngeal cancers. PMID- 22782221 TI - Radiographic imaging of human papillomavirus related carcinomas of the oropharynx. AB - Imaging, especially contrast-enhanced computed tomography (CECT) for anatomy and positron emission tomography (PET) with labeled (18)F fluorodeoxyglucose for physiologic detail, is critical for staging carcinomas of the oropharynx. As the incidence of human papillomavirus (HPV) infection and related carcinomas of the tonsil and base of tongue (BOT) increases, experience with CECT and PET for staging HPV+ tumors is growing. No imaging modality, however, can determine whether the tumor is HPV+. There are some unique challenges posed by HPV+ oropharyngeal squamous cell carcinoma (SCC). In most locations of the head and neck, a malignancy enhances more than surrounding normal structures, which facilitates tumor mapping. Unfortunately, normal lymphoid tissue of the oropharynx, in the BOT and palatine tonsillar fossa, enhances on CECT and gadolinium enhanced magnetic resonance imaging in a manner similar to SCC. The primary tumor may be small or even occult at presentation, and easily over-looked on CECT. PET coupled with CECT has made a true "unknown primary" very rare, as the metabolically active tumor is almost always detectable on PET. The nodal metastases, so common with HPV+ SCC, can be truly cystic; and as such, can be misdiagnosed as a second branchial cleft cyst, a congenital benign lesion. These pitfalls, coupled with the complex anatomy of the upper aerodigestive tract, make staging these tumors difficult. In this monograph we describe the anatomy of the oropharynx and review the imaging modalities available for staging. Figures highlight the points raised in the text. PMID- 22782222 TI - Morphologic features of conventional squamous cell carcinoma of the oropharynx: 'keratinizing' and 'nonkeratinizing' histologic types as the basis for a consistent classification system. AB - Morphologic assessment is one of the most basic tools that pathologists use to classify tumors. Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx has unique morphologic features that can be readily recognized under the microscope. Yet, these features are not widely recognized or uniformly reported. In our practice, we group oropharyngeal squamous cell carcinomas into 'nonkeratinizing', 'nonkeratinizing with maturation', and 'keratinizing' histologic types. The 'nonkeratinizing' type has a very strong association with HPV, while the 'keratinizing' type has a weaker association with the virus. 'Nonkeratinizing with maturation' is intermediate but much more closely related to the 'nonkeratinizing' type. This classification system parallels that of sinonasal and nasopharyngeal squamous cell carcinomas where nonkeratinizing squamous cell carcinomas are widely recognized histologic variants. This review will discuss this classification system and its utility in routine clinical practice. PMID- 22782223 TI - The morphologic profile of HPV-related head and neck squamous carcinoma: implications for diagnosis, prognosis, and clinical management. AB - Much recent attention has highlighted a subset of head and neck squamous cell carcinomas (HNSCCs) related to the human papillomavirus (HPV) that is characterized by an epidemiologic, demographic, and clinical profile that deviates from the profile of conventional non-HPV-related HNSCC. Lost in the dash to develop and implement diagnostic assays to detect the presence of HPV in HNSCCs is the unpretentious observation that these HPV-HNSCCs are also distinctive with respect to their microscopic appearance, and that an awareness of these characteristic morphologic features can facilitate the diagnosis of HPV related HNSCC (HPV-HNSCC). This review will delineate the microscopic appearance of HPV-HNSCC, spotlight ways in which the misinterpretation of these microscopic features can lead to diagnostic confusion, and provide recommendations for appropriate terminology when diagnosing HPV-HNSCC. PMID- 22782224 TI - HPV-related squamous cell carcinoma variants in the head and neck. AB - The great majority of HPV-related carcinoma of the oropharynx is nonkeratinizing squamous cell carcinoma. More recently, an increasing number of squamous cell carcinoma variants that are HPV positive are being reported in the oropharynx, as well as in other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, questions raised include whether the virus is biologically active and involved in the pathogenesis of these tumors, and whether there are clinical implications with regard to patient outcome and treatment modality changes that may be needed in HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here include: basaloid squamous cell carcinoma, undifferentiated carcinoma, adenosquamous carcinoma, papillary squamous carcinoma, and small cell carcinoma. Some investigations have suggested a favorable prognosis in some variants, analogous to that of the conventional nonkeratinizing (basaloid) carcinoma, while others showed poorer outcome. So far, the number of studies on this subject is limited and the number of cases evaluated in each investigation is few. Because of this, it is prudent at this stage not to alter management protocols as a result of identification of HPV in these variants and to await additional studies. PMID- 22782225 TI - HPV detection methods in head and neck cancer. AB - Human papillomavirus (HPV) infection is emerging as a major prognostic and predictive marker in head and neck squamous cell carcinoma (HNSCC). Researches are focused on the development of HPV detection assays specially designed for HNSCC. The HPV diagnosis in these tumours is relevant toprognosis even in an already-developed tumour, whereas in the cervix, where the HPV is the cause of almost all tumours, this information has less clinical relevance. The better outcome of HPV-associated HNSCC raises the question about the best methodologies to distinguish between HPV and non-HPV-associated SCC. However, no consensus has been reached on the optimal way to identify HPV-associated SCC and ancillary studies have utilised many different methodologies, including HPV polymerase chain reaction testing, HPV in situ hybridization analysis, immunohistochemical staining for p16, and newer techniques that are currently under investigation. The objective of this review is to explain and give examples of various techniques of HPV detection highlighting how they might be used clinically. Although currently insufficiently specific due to the possibility of HPV infection originating at other sites, methodologies utilising serum and plasma to measure HPV infection will also be described, mostly for their potential future development and use. Finally, DNA/RNA microarray platforms will be briefly summarized for their capacity to identify the profile of molecular changes in any particular HPV+/HPV- cancer. In this way, it is expected to be possible to correlate the appropriate transcriptome-based diagnosis to the patients' specific cancer risk. PMID- 22782226 TI - p16 Immunohistochemistry as a standalone test for risk stratification in oropharyngeal squamous cell carcinoma. AB - It is widely acknowledged that human papillomavirus (HPV)-related oropharyngeal carcinoma is a biologically unique form of head and neck cancer that should be singled out and treated differently. It is now incumbent to find a test (or combination of tests) that accurately identifies cancers with the associated favorable prognosis for proper patient counseling and management and for placing patients in the correct treatment arms in the emerging clinical trials that are attempting to establish unique treatment types and approaches. The test (or combination of tests) that are utilized must be widely available, reliable, easy to interpret, and well-validated. While HPV-specific testing seems completely logical to use as a single test or one of a combination of tests, it turns out to be quite complicated in practice. Because of the different forms of the virus, the differing types of HPV-specific tests can give different information. HPV DNA, RNA, and protein assays have varying sensitivities for virus detection and also varying availability from formalin-fixed, paraffin-embedded tissue. Since p16 protein over expression is very sensitive for the presence of transcriptionally-active HPV and since it correlates strongly with patient outcomes, is widely available, and easy to interpret, it appears to currently be the single test that combines all of the desired attributes in a risk stratification marker for widespread implementation in clinical and research study settings. This article will review the literature on p16 immunohistochemistry and its relation to HPV-specific testing, discuss some practical issues related to its implementation, and present the case for why it should be the single test used for this purpose. PMID- 22782227 TI - HPV specific testing: a requirement for oropharyngeal squamous cell carcinoma patients. AB - Human papillomavirus (HPV) testing is now recommended as part of the work up for patients with oropharyngeal squamous cell carcinoma (OPSCC) and those patients with cervical lymph node metastasis of unknown origin. The laboratory testing strategy should accurately assess the presence or absence of oncogenic HPV infection in routinely collected tumour samples that are subject to standard fixation protocols, alcohol-fixed cytological preparations and formalin-fixed tissue samples. The HPV status should correlate with biologically relevant outcome measures such as overall, disease-specific and disease-free survival. Whilst increased expression of p16 by immunohistochemistry is considered to be a surrogate marker of oncogenic HPV infection and is a validated independent prognostic biomarker, only HPV specific tests provide definitive evidence of the aetiological agent. We provide an overview of HPV testing in OPSCC, justifying the use of HPV specific tests. We examine the analytical accuracy of HPV specific tests against the 'reference' test--high risk HPV mRNA in fresh tissue--and contrast this with the performance of p16 immunohistochemistry as a stand alone test. We highlight the added value of HPV specific tests in prognostication, clinical trial design, and population-based disease surveillance. We consider that HPV specific testing is the starting point for developing increasingly informative biomarker panels in the context of 'stratified medicine'. We briefly frame test information in the context of disclosure of HPV status to patients. We conclude that only a testing strategy that includes HPV specific tests can deliver more effective care for patients with OPSCC. The international head and neck oncology community should work together to clearly define the minimum requirements for assigning a diagnosis of HPV-related OPSCC in order to ensure consistent reporting of this emerging and increasingly prevalent disease. PMID- 22782228 TI - Primary chemotherapy and radiation as a treatment strategy for HPV-positive oropharyngeal cancer. AB - The incidence of human papillomavirus-positive oropharyngeal cancer (HPV/OPSCC) is rapidly increasing, which will represent a major public health burden for decades to come. Although HPV/OPSCC is generally associated with a better prognosis than HPV-negative OPSCC, the survival rate of individuals with higher risk clinical and pathologic features remains unchanged. Emerging evidence suggests that HPV/OPSCC is pathologically and molecularly distinct from HPV negative OPSCC. This review focuses on summarizing treatment strategies for HPV/OPSCC by reviewing the peer-reviewed literature and noting ongoing and planned clinical trials in this disease. We also discuss the potential of designing targeted therapy based on the recent genomic findings of HPV/OPSCC. PMID- 22782229 TI - The role for surgical management of HPV-related oropharyngeal carcinoma. AB - Human papillomavirus (HPV)-associated oropharyngeal carcinoma has become the predominate cause of oropharyngeal carcinoma in the United States and Europe. Management of this disease is controversial. Traditional open surgical techniques gave way to concurrent chemoradiotherapy following several American and European organ-preservation trials suggesting that both modalities were equally efficacious. More recently, minimally invasive surgical techniques have gained popularity. These techniques provide an opportunity to achieve a complete surgical resection without the treatment-related morbidity associated with open surgery. Proponents of this technique contend that transoral surgical techniques provide a means to analyze the tumor tissue, prognosticate, and personally direct therapy. Skeptics suggest that HPV-associated oropharyngeal carcinoma responds well to chemoradiotherapy and that surgery may not provide a treatment advantage. Both approaches provide a unique perspective and both are currently being studied under trial. PMID- 22782231 TI - Future directions in research, treatment and prevention of HPV-related squamous cell carcinoma of the head and neck. AB - The causative relationship between high-risk HPV and OSCC is well-established. HPV-associated OSCC represents a distinct disease entity compared to tobacco associated ones. These virus-associated cancers continuously express the HPV E6 and E7 viral oncogenes even in advanced stages, and repression of viral oncogene expression can prevent the growth or survival of cancer cells. This finding raises the possibility that even late-stage HPV-associated OSCC can be cured by HPV-targeted approaches, such as medicines that interfere with the expression or function of viral oncoproteins, and therapeutic vaccines that elicit a cytolytic immune response to cells expressing these oncoproteins. The demonstration that high-risk HPVs are causally associated with a subset of OSCC has allowed the development of preventive and therapeutic strategies aimed at reducing the incidence and mortality of this disease. The better outcome of HPV-associated OSCC raises the question as to whether similar results can be achieved with less treatment. An important aim of novel approaches for favorable-prognosis, HPV associated cancers will be minimization of devastating side effects of intensified treatment developed for poor prognostic subsets. Clinical trials are studying the potential for de-escalation of radiation therapy in HPV + OSCC in the setting of different chemoradiotherapy regimens. The role of cetuximab in HPV associated OSCC needs to be explored in prospective clinical trials. This review summarizes the main events of HPV-induced carcinogenesis with an emphasis on the implications of these carcinogenic mechanisms on research, treatment and prevention of HPV-associated OSCC. PMID- 22782232 TI - Single oocyte bisulfite mutagenesis. AB - Epigenetics encompasses all heritable and reversible modifications to chromatin that alter gene accessibility, and thus are the primary mechanisms for regulating gene transcription. DNA methylation is an epigenetic modification that acts predominantly as a repressive mark. Through the covalent addition of a methyl group onto cytosines in CpG dinucleotides, it can recruit additional repressive proteins and histone modifications to initiate processes involved in condensing chromatin and silencing genes. DNA methylation is essential for normal development as it plays a critical role in developmental programming, cell differentiation, repression of retroviral elements, X-chromosome inactivation and genomic imprinting. One of the most powerful methods for DNA methylation analysis is bisulfite mutagenesis. Sodium bisulfite is a DNA mutagen that deaminates cytosines into uracils. Following PCR amplification and sequencing, these conversion events are detected as thymines. Methylated cytosines are protected from deamination and thus remain as cytosines, enabling identification of DNA methylation at the individual nucleotide level. Development of the bisulfite mutagenesis assay has advanced from those originally reported towards ones that are more sensitive and reproducible. One key advancement was embedding smaller amounts of DNA in an agarose bead, thereby protecting DNA from the harsh bisulfite treatment. This enabled methylation analysis to be performed on pools of oocytes and blastocyst-stage embryos. The most sophisticated bisulfite mutagenesis protocol to date is for individual blastocyst-stage embryos. However, since blastocysts have on average 64 cells (containing 120-720 pg of genomic DNA), this method is not efficacious for methylation studies on individual oocytes or cleavage-stage embryos. Taking clues from agarose embedding of minute DNA amounts including oocytes, here we present a method whereby oocytes are directly embedded in an agarose and lysis solution bead immediately following retrieval and removal of the zona pellucida from the oocyte. This enables us to bypass the two main challenges of single oocyte bisulfite mutagenesis: protecting a minute amount of DNA from degradation, and subsequent loss during the numerous protocol steps. Importantly, as data are obtained from single oocytes, the issue of PCR bias within pools is eliminated. Furthermore, inadvertent cumulus cell contamination is detectable by this method since any sample with more than one methylation pattern may be excluded from analysis. This protocol provides an improved method for successful and reproducible analyses of DNA methylation at the single-cell level and is ideally suited for individual oocytes as well as cleavage-stage embryos. PMID- 22782230 TI - Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review. AB - Perhaps one of the most important developments in head and neck oncology of the past decade is the demonstration that patients with human papillomavirus (HPV) mediated oropharyngeal cancers have significantly improved outcomes, compared to HPV-negative counterpart patients. This has become the basis for clinical trials investigating the impact on "treatment deintensification" for patients with HPV mediated oropharyngeal cancers. Unfortunately, the significance of HPV in non oropharyngeal head and neck cancers is much less certain. Our goal is to systematically review the published data regarding the role HPV in carcinomas of the oral cavity, larynx, sinonasal tract and nasopharynx with respect to HPV detection frequency, viral activity, and association with outcome. We also present preliminary data on HPV16/18 transcriptional status in oral cavity carcinomas, as well as salivary gland neoplasia, as determined by nested reverse transcription PCR for HPV E6/E7 RNA. The weighted prevalence (WP) of HPV DNA detection in 4,195 oral cavity cancer patients is 20.2 %, (95 % CI 16.0 %, 25.2 %). HPV16 is the most common type detected. Importantly, no data currently demonstrates a significant association between the presence of HPV DNA and improved outcome. The WP of HPV DNA in 1,712 laryngeal cancer patients is 23.6 %, (95 % CI 18.7 %, 29.3 %). Similarly, no association has yet been demonstrated between HPV DNA status and outcome. The WP of HPV DNA detection in 120 sinonasal cancer patients is 29.6 % (95 % CI 17.8 %, 44.9 %), and in 154 nasopharyngeal carcinoma patients is 31.1 %, (95 % CI 20.3 %, 44.5 %). Recent preliminary data also suggests an association between HPV and certain salivary gland neoplasms. The clinical significance of these findings is unclear. The published data strongly support the need for studies on patients with oral and laryngeal carcinomas that will be powered to find any differences in clinical outcome with respect to HR-HPV and p16 overexpression. PMID- 22782233 TI - Neuritin is expressed in Schwann cells and down-regulated in apoptotic Schwann cells under hyperglycemia. AB - We aimed to explore neuritin expression in Schwann cells under different glucose conditions. Expression of neuritin at the levels of transcription and translation in purified Schwann cells was detected and measured using reverse transcriptase (RT) (quantitative) polymerase chain reaction (PCR) and western blot. Apoptosis of Schwann cells was measured by flow cytometry using Fluorescence Activated Cell Sorter (FACS) analysis and caspase fluorometric assay. Neuritin mRNA and protein were detected in cultured primary Schwann cells. Neuritin was identified as cell membrane form of protein and predominately as secreted or solube form of protein. Neuritin was significantly lower in 150 mM glucose condition, and more significantly lower in 300 mM glucose, than 5.6 mM glucose condition at 36 hours and especially at 48 hours of the culture, respectively (P < 0.05-0.01). In contrast to 5.6 mM glucose, obvious apoptosis of Schwann cells was demonstrated at 42 hours in 300 mM glucose condition and at 48 hours in 150 mM glucose, respectively (P < 0.05-0.01). Neuritin and apoptosis were correlated in a power regression (P < 0.01). 5.6 mM glucose cultured cells did not show these obvious changes during the experiment. It is concluded that neuritin mRNA and protein were expressed and down-regulated in Schwann cells under high-glucose concentration and the down-regulation may contribute to apopotosis of Schwann cells. PMID- 22782234 TI - High resolution methyl selective 13C-NMR of proteins in solution and solid state. AB - New 13C-detected NMR experiments have been devised for molecules in solution and solid state, which provide chemical shift correlations of methyl groups with high resolution, selectivity and sensitivity. The experiments achieve selective methyl detection by exploiting the one bond J-coupling between the 13C-methyl nucleus and its directly attached 13C spin in a molecule. In proteins such correlations edit the 13C-resonances of different methyl containing residues into distinct spectral regions yielding a high resolution spectrum. This has a range of applications as exemplified for different systems such as large proteins, intrinsically disordered polypeptides and proteins with a paramagnetic centre. PMID- 22782235 TI - NMR structure note: N-terminal domain of Thermus thermophilus CdnL. PMID- 22782237 TI - Phenotypic plasticity as an index of drought tolerance in three Patagonian steppe grasses. AB - BACKGROUND AND AIMS: Despite general agreement regarding the adaptive importance of plasticity, evidence for the role of environmental resource availability in plants is scarce. In arid and semi-arid environments, the persistence and dominance of perennial species depends on their capacity to tolerate drought: tolerance could be given on one extreme by fixed traits and, on the other, by plastic traits. To understand drought tolerance of species it is necessary to know the plasticity of their water economy-related traits, i.e. the position in the fixed-plastic continuum. METHODS: Three conspicuous co-existing perennial grasses from a Patagonian steppe were grown under controlled conditions with four levels of steady-state water availability. Evaluated traits were divided into two groups. The first was associated with potential plant performance and correlated with fitness, and included above-ground biomass, total biomass, tillering and tiller density at harvest. The second group consisted of traits associated with mechanisms of plant adjustment to environmental changes and included root biomass, shoot/root ratio, tiller biomass, length of total elongated leaf, length of yellow tissue divided by time and final length divided by the time taken to reach final length. KEY RESULTS AND CONCLUSIONS: The most plastic species along this drought gradient was the most sensitive to drought, whereas the least plastic and slowest growing was the most tolerant. This negative relationship between tolerance and plasticity was true for fitness-related traits but was trait-dependent for underlying traits. Remarkably, the most tolerant species had the highest positive plasticity (i.e. opposite to the default response to stress) in an underlying trait, directly explaining its drought resistance: it increased absolute root biomass. The niche differentiation axis that allows the coexistence of species in this group of perennial dryland grasses, all limited by soil surface moisture, would be a functional one of fixed versus plastic responses. PMID- 22782238 TI - Multi-stemmed trees of Nothofagus pumilio second-growth forest in Patagonia are formed by highly related individuals. AB - BACKGROUND AND AIMS: Multi-stemmed trees (tree clusters) in Nothofagus pumilio, a dominant tree species in Patagonia, are very uncommon and are restricted to the edge of second-growth forests following human-provoked fires. No vegetative reproduction has been reported so far. The genetic structure of multi-stemmed trees of this species was investigated and it was hypothesized that genets within a cluster were more closely related than average in the population. METHODS: Fifteen clusters (composed of at least three purported stems) and 15 single trees were sampled at the edge of a second-growth forest and genotyped using two amplified fragment length polymorphism (AFLP) primer pairs. We obtained 119 polymorphic markers that allowed clonality to be determined, together with sibship structure and relatedness among samples. KEY RESULTS: Clonality was detected in seven clusters but all clusters had at least two different genotypes. Full sibs were found exclusively within clusters and in all clusters. Within a cluster, stems that were not identified as full sibs were often half sibs. Relatedness values for the full sibs and half sibs were higher than the theoretical values of 0.5 and 0.25 but the relatedness between clusters was very low. CONCLUSIONS: Tree clusters that are merged at the edge of the second-growth forest of N. pumilio are composed of stems of the same genotype and of other genotypes that are highly related (but not always). It is suggested that this peculiar genetic structure results from a combination of several causes, including selection for merging of related individuals. PMID- 22782239 TI - Oil-producing flowers within the Iridoideae (Iridaceae): evolutionary trends in the flowers of the New World genera. AB - BACKGROUND AND AIMS: Oil-producing flowers related to oil-bee pollination are a major innovation in Neotropical and Mexican Iridaceae. In this study, phylogenetic relationships were investigated among a wide array of New World genera of the tribes Sisyrinchieae, Trimezieae and Tigridieae (Iridaceae: Iridoideae) and the evolution of floral glandular structures, which are predominantly trichomal elaiophores, was examined in relation to the diversification of New World Iridaceae. METHODS: Phylogenetic analyses based on seven molecular markers obtained from 97 species were conducted to produce the first extensive phylogeny of the New World tribes of subfamily Iridoideae. The resulting phylogenetic hypothesis was used to trace the evolutionary history of glandular structures present in the flowers of numerous species in each tribe. Hypotheses of differential diversification rates among lineages were also investigated using both topological and Binary-State Speciation and Extinction methods. KEY RESULTS AND CONCLUSIONS: Floral glandular structures and especially trichomal elaiophores evolved multiple times independently in the American tribes of Iridoideae. The distribution pattern of species displaying glandular trichomes across the phylogeny reveals lability in the pollination system and suggests that these structures may have played a significant role in the diversification of the Iridoideae on the American continent. PMID- 22782240 TI - Branching habit and the allocation of reproductive resources in conifers. AB - BACKGROUND AND AIMS: Correlated relationships between branch thickness, branch density, and twig and leaf size have been used extensively to study the evolution of plant canopy architecture, but fewer studies have explored the impact of these relationships on the allocation of reproductive resources. This study quantifies pollen cone production in conifers, which have similar basic reproductive biology but vary dramatically in branching habit, in order to test how differences in branch diameter influence pollen cone size and the density with which they are deployed in the canopy. METHODS: Measurements of canopy branch density, the number of cones per branch and cone size were used to estimate the amount of pollen cone tissues produced by 16 species in three major conifer clades. The number of pollen grains produced was also estimated using direct counts from individual pollen cones. KEY RESULTS: The total amount of pollen cone tissues in the conifer canopy varied little among species and clades, although vegetative traits such as branch thickness, branch density and pollen cone size varied over several orders of magnitude. However, branching habit controls the way these tissues are deployed: taxa with small branches produce small pollen cones at a high density, while taxa with large branches produce large cones relatively sparsely. CONCLUSIONS: Conifers appear to invest similar amounts of energy in pollen production independent of branching habit. However, similar associations between branch thickness, branch density and pollen cone size are seen across conifers, including members of living and extinct groups not directly studied here. This suggests that reproductive features relating to pollen cone size are in large part a function of the evolution of vegetative morphology and branching habit. PMID- 22782241 TI - The interplay of stress and mowing disturbance for the intensity and importance of plant interactions in dry calcareous grasslands. AB - BACKGROUND AND AIMS: There is still debate regarding the direction and strength of plant interactions under intermediate to high levels of stress. Furthermore, little is known on how disturbance may interact with physical stress in unproductive environments, although recent theory and models have shown that this interplay may induce a collapse of plant interactions and diversity. The few studies assessing such questions have considered the intensity of biotic interactions but not their importance, although this latter concept has been shown to be very useful for understanding the role of interactions in plant communities. The objective of this study was to assess the interplay between stress and disturbance for plant interactions in dry calcareous grasslands. METHODS: A field experiment was set up in the Dordogne, southern France, where the importance and intensity of biotic interactions undergone by four species were measured along a water stress gradient, and with and without mowing disturbance. KEY RESULTS: The importance and intensity of interactions varied in a very similar way along treatments. Under undisturbed conditions, plant interactions switched from competition to neutral with increasing water stress for three of the four species, whereas the fourth species was not subject to any significant biotic interaction along the gradient. Responses to disturbance were more species-specific; for two species, competition disappeared with mowing in the wettest conditions, whereas for the two other species, competition switched to facilitation with mowing. Finally, there were no significant interactions for any species in the disturbed and driest conditions. CONCLUSIONS: At very high levels of stress, plant performances become too weak to allow either competition or facilitation and disturbance may accelerate the collapse of interactions in dry conditions. The results suggest that the importance and direction of interactions are more likely to be positively related in stressful environments. PMID- 22782242 TI - Disorganization of F-actin cytoskeleton precedes vacuolar disruption in pollen tubes during the in vivo self-incompatibility response in Nicotiana alata. AB - BACKGROUND AND AIMS: The integrity of actin filaments (F-actin) is essential for pollen-tube growth. In S-RNase-based self-incompatibility (SI), incompatible pollen tubes are inhibited in the style. Consequently, research efforts have focused on the alterations of pollen F-actin cytoskeleton during the SI response. However, so far, these studies were carried out in in vitro-grown pollen tubes. This study aimed to assess the timing of in vivo changes of pollen F-actin cytoskeleton taking place after compatible and incompatible pollinations in Nicotiana alata. To our knowledge, this is the first report of the in vivo F actin alterations occurring during pollen rejection in the S-RNase-based SI system. METHODS: The F-actin cytoskeleton and the vacuolar endomembrane system were fluorescently labelled in compatibly and incompatibly pollinated pistils at different times after pollination. The alterations induced by the SI reaction in pollen tubes were visualized by confocal laser scanning microscopy. KEY RESULTS: Early after pollination, about 70 % of both compatible and incompatible pollen tubes showed an organized pattern of F-actin cables along the main axis of the cell. While in compatible pollinations this percentage was unchanged until pollen tubes reached the ovary, pollen tubes of incompatible pollinations underwent gradual and progressive F-actin disorganization. Colocalization of the F-actin cytoskeleton and the vacuolar endomembrane system, where S-RNases are compartmentalized, revealed that by day 6 after incompatible pollination, when the pollen-tube growth was already arrested, about 80 % of pollen tubes showed disrupted F-actin but a similar percentage had intact vacuolar compartments. CONCLUSIONS: The results indicate that during the SI response in Nicotiana, disruption of the F-actin cytoskeleton precedes vacuolar membrane breakdown. Thus, incompatible pollen tubes undergo a sequential disorganization process of major subcellular structures. Results also suggest that the large pool of S RNases released from vacuoles acts late in pollen rejection, after significant subcellular changes in incompatible pollen tubes. PMID- 22782243 TI - Soil water content and patterns of allocation to below- and above-ground biomass in the sexes of the subdioecious plant Honckenya peploides. AB - BACKGROUND AND AIMS: Dioecious plants often show sex-specific differences in growth and biomass allocation. These differences have been explained as a consequence of the different reproductive functions performed by the sexes. Empirical evidence strongly supports a greater reproductive investment in females. Sex differences in allocation may determine the performance of each sex in different habitats and therefore might explain the spatial segregation of the sexes described in many dimorphic plants. Here, an investigation was made of the sexual dimorphism in seasonal patterns of biomass allocation in the subdioecious perennial herb Honckenya peploides, a species that grows in embryo dunes (i.e. the youngest coastal dune formation) and displays spatial segregation of the sexes at the studied site. The water content in the soil of the male- and female plant habitats at different times throughout the season was also examined. METHODS: The seasonal patterns of soil-water availability and biomass allocation were compared in two consecutive years in male and female H. peploides plants by collecting soil and plant samples in natural populations. Vertical profiles of below-ground biomass and water content were studied by sampling soil in male- and female-plant habitats at different soil depths. KEY RESULTS: The sexes of H. peploides differed in their seasonal patterns of biomass allocation to reproduction. Males invested twice as much in reproduction than females early in the season, but sexual differences became reversed as the season progressed. No differences were found in above-ground biomass between the sexes, but the allocation of biomass to below-ground structures varied differently in depth for males and females, with females usually having greater below-ground biomass than males. In addition, male and female plants of H. peploides had different water content profiles in the soil where they were growing and, when differences existed (usually in the upper layers of the soil), the water content of the soil was higher for the female plants had than for the male plants. CONCLUSIONS: Sex differential timing of investment in reproduction and differential availability and use of resources from the soil (particularly water) are factors that probably offset the costs of reproduction in the above-ground growth in males and females of H. peploides. The results suggest that the patterns of spatial segregation of the sexes observed in H. peploides may contribute to maximize each sex's growth and reproduction. PMID- 22782245 TI - Hydrogen gas storage in fluorinated ultramicroporous tunnel crystal. AB - We report hydrogen storage at an ordinary pressure due to a bottle-neck effect of an ultramicroporous crystal. Stored hydrogen was kept at an ordinary pressure below -110 degrees C. The amounts of stored hydrogen gas linearly correlated with the initial pressures. These phenomena suggested the ultramicroporous tunnels worked as a molecular gas cylinder. PMID- 22782244 TI - Nitric oxide is involved in light-specific responses of tomato during germination under normal and osmotic stress conditions. AB - BACKGROUND AND AIMS: Nitric oxide (NO) is involved in the signalling and regulation of plant growth and development and responses to biotic and abiotic stresses. The photoperiod-sensitive mutant 7B-1 in tomato (Solanum lycopersicum) showing abscisic acid (ABA) overproduction and blue light (BL)-specific tolerance to osmotic stress represents a valuable model to study the interaction between light, hormones and stress signalling. The role of NO as a regulator of seed germination and ABA-dependent responses to osmotic stress was explored in wild type and 7B-1 tomato under white light (WL) and BL. METHODS: Germination data were obtained from the incubation of seeds on germinating media of different composition. Histochemical analysis of NO production in germinating seeds was performed by fluorescence microscopy using a cell-permeable NO probe, and endogenous ABA was analysed by mass spectrometry. KEY RESULTS: The NO donor S nitrosoglutathione stimulated seed germination, whereas the NO scavenger 2-phenyl 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) had an inhibitory effect. Under WL in both genotypes, PTIO strongly suppressed germination stimulated by fluridone, an ABA inhibitor. The stimulatory effect of the NO donor was also observed under osmotic stress for 7B-1 seeds under WL and BL. Seed germination inhibited by osmotic stress was restored by fluridone under WL, but less so under BL, in both genotypes. This effect of fluridone was further modulated by the NO donor and NO scavenger, but only to a minor extent. Fluorescence microscopy using the cell-permeable NO probe DAF-FM DA (4-amino-5-methylamino-2',7' difluorofluorescein diacetate) revealed a higher level of NO in stressed 7B-1 compared with wild-type seeds. CONCLUSIONS: As well as defective BL signalling, the differential NO-dependent responses of the 7B-1 mutant are probably associated with its high endogenous ABA concentration and related impact on hormonal cross-talk in germinating seeds. These data confirm that light controlled seed germination and stress responses include NO-dependent signalling. PMID- 22782246 TI - Conformational technique for non-anatomic resection of liver lesions. AB - Safe margin-negative hepatic resection with maximal preservation of normal liver parenchyma is the primary operative objective in treating patients with metastatic or primary liver malignancies. A technique to perform non-anatomic liver resection(s) for large lesions that may involve major hepatic vascular structures is herein described. This technique employs linear cutting stapler technology and specific mobilization of the liver to perform single or multiple large spherical resections of liver lesions. PMID- 22782247 TI - Multi-catalysis reactions: new prospects and challenges of biotechnology to valorize lignin. AB - Considerable effort has been dedicated to the chemical depolymerization of lignin, a biopolymer constituting a possible renewable source for aromatic value added chemicals. However, these efforts yielded limited success up until now. Efficient lignin conversion might necessitate novel catalysts enabling new types of reactions. The use of multiple catalysts, including a combination of biocatalysts, might be necessary. New perspectives for the combination of bio- and inorganic catalysts in one-pot reactions are emerging, thanks to green chemistry-driven advances in enzyme engineering and immobilization and new chemical catalyst design. Such combinations could offer several advantages, especially by reducing time and yield losses associated with the isolation and purification of the reaction products, but also represent a big challenge since the optimal reaction conditions of bio- and chemical catalysis reactions are often different. This mini-review gives an overview of bio- and inorganic catalysts having the potential to be used in combination for lignin depolymerization. We also discuss key aspects to consider when combining these catalysts in one-pot reactions. PMID- 22782248 TI - Characterization of rhizosphere prokaryotic diversity in a horizontal subsurface flow constructed wetland using a PCR cloning-sequencing based approach. AB - Performance of biological wastewater treatment systems may be related to the composition and activity of microbial populations they contain. However, little information is known regarding microbial community inhabiting these ecosystems. The purpose of this study was to investigate archaeal and bacterial diversity, using cultivation-independent molecular techniques, in a constructed wetland receiving domestic wastewater. Two 16S rRNA gene libraries were constructed using total genomic DNA and amplified by PCR using primers specific for archaeal and bacterial domains. A high microbial diversity was detected. The Proteobacteria phylum is the most abundant and diversified phylogenetic group representing 31.3 % of the OTUs, followed by the Bacteroidetes (14.8 %), Planctomycetales (13.8 %), Actinobacteria (12 %), and Chloroflexi (8.2 %). Sequences affiliated with minor phylogenetic divisions such as the TM7, Nitrospira, OP10, and BRC1 are represented by <6 % of total OTUs. The Archaea domain was represented by the Thaumarchaeota phylum dominated by the Candidatus Nitrososphaera genus. PMID- 22782249 TI - Improvement of bacterial cellulose production by manipulating the metabolic pathways in which ethanol and sodium citrate involved. AB - Nowadays, bacterial cellulose has played more and more important role as new biological material for food industry and medical and industrial products based on its unique properties. However, it is still a difficult task to improve the production of bacterial cellulose, especially a large number of byproducts are produced in the metabolic biosynthesis processes. To improve bacterial cellulose production, ethanol and sodium citrate are added into the medium during the fermentation, and the activities of key enzymes and concentration of extracellular metabolites are measured to assess the changes of the metabolic flux of the hexose monophosphate pathway (HMP), the Embden-Meyerhof-Parnas pathway (EMP), and the tricarboxylic acid cycle (TCA). Our results indicate that ethanol functions as energy source for ATP generation at the early stage of the fermentation in the HMP pathway and the supplementation of ethanol significantly reduces glycerol generation (a major byproduct). While in the EMP pathway, sodium citrate plays a key role, and its supplementation results in the byproducts (mainly acetic acid and pyruvic acid) entering the gluconeogenesis pathway for cellulose synthesis. Furthermore, by adding ethanol and sodium citrate, the main byproduct citric acid in the TCA cycle is also reduced significantly. It is concluded that bacterial cellulose production can be improved by increasing energy metabolism and reducing the formation of metabolic byproducts through the metabolic regulations of the bypasses. PMID- 22782250 TI - Rhamnolipid production: effect of oxidative stress on virulence factors and proteome of Pseudomonas aeruginosa PA1. AB - Under specific environmental conditions, Pseudomonas aeruginosa produces a biodegradable surfactant rhamnolipid. Evidences suggest that this biosurfactant is involved in protecting cells against oxidative stress; however, the effects of oxidative stress on its production and other virulence factors are still unclear. Here we show that rhamnolipid production is dependent on the aeration surface when P. aeruginosa is cultured in shaken flasks, as well as in production of elastases and alkaline proteases. The production of alginate, lipase, and pyocyanin was not detected in our shaken-flask experiments. P. aeruginosa was treated with hydrogen peroxide to trigger its oxidative stress response, and the proteome profile was analyzed. We identified 14 proteins that were expressed differently between samples that were treated and not treated with peroxide; these proteins are potentially involved in the rhamnolipid production/secretion pathway and oxidative stress. PMID- 22782251 TI - Molecular tools for deciphering the microbial community structure and diversity in rumen ecosystem. AB - Rumen microbial community comprising of bacteria, archaea, fungi, and protozoa is characterized not only by the high population density but also by the remarkable diversity and the most complex microecological interactions existing in the biological world. This unprecedented biodiversity is quite far from full elucidation as only about 15-20 % of the rumen microbes are identified and characterized till date using conventional culturing and microscopy. However, the last two decades have witnessed a paradigm shift from cumbersome and time consuming classical methods to nucleic acid-based molecular approaches for deciphering the rumen microbial community. These techniques are rapid, reproducible and allow both the qualitative and quantitative assessment of microbial diversity. This review describes the different molecular methods and their applications in elucidating the rumen microbial community. PMID- 22782252 TI - Modulating heterologous protein production in yeast: the applicability of truncated auxotrophic markers. AB - The use of auxotrophic Saccharomyces cerevisiae strains for improved production of a heterologous protein was examined. Two different marker genes were investigated, encoding key enzymes in the metabolic pathways for amino acid (LEU2) and pyrimidine (URA3) biosynthesis, respectively. Expression plasmids, carrying the partly defective selection markers LEU2d and URA3d, were constructed. Two CEN.PK-derived strains were chosen and insulin analogue precursor was selected as a model protein. Different truncations of the LEU2 and URA3 promoters were used as the mean to titrate the plasmid copy number and thus the recombinant gene dosage in order to improve insulin productivity. Experiments were initially carried out in batch mode to examine the stability of yeast transformants and to select high yielding mutants. Next, chemostat cultivations were run at high cell density to address industrial applicability and long-term expression stability of the transformants. We found that the choice of auxotrophic marker is crucial for developing a yeast expression system with stable heterologous protein production. The incremental truncation of the URA3 promoter led to higher plasmid copy numbers and IAP yields, whereas the truncation of the LEU2 promoter caused low plasmid stability. We show that the modification of the level of the recombinant gene dosage by varying the degree of promoter truncation can be a strong tool for optimization of productivity. The application of the URA3d-based expression systems showed a high potential for industrial protein production and for further academic studies. PMID- 22782253 TI - Recent research on 3-phenyllactic acid, a broad-spectrum antimicrobial compound. AB - 3-Phenyllactic acid (PLA), which is an organic acid widely existing in honey and lactic acid bacteria fermented food, can be produced by many microorganisms, especially lactic acid bacteria. It was proved as an ideal antimicrobial compound with broad and effective antimicrobial activity against both bacteria and fungi. In addition, it could be used as feed additives to replace antibiotics in livestock feeds. This article presented a review of recent studies on the existing resource, antimicrobial activity, and measurement of PLA. In addition, microorganism strains and dehydrogenases producing PLA were reviewed in detail, the metabolic pathway and regulation of PLA synthesis in LAB strains were discussed, and high-level bioproduction of PLA by microorganism fermentation was also summarized. PMID- 22782254 TI - Seedling development in a Brassica napus diversity set and its relationship to agronomic performance. AB - Brassica napus L. is the leading European oilseed crop and has therefore a high economical importance. The objectives of our study were to examine (1) the patterns of phenotypic diversity in a species-wide B. napus germplasm set of 518 inbreds with respect to various seedling development, agronomic, and seed quality traits as well as (2) the interrelationship of the examined traits and their use in selection on correlated traits. The B. napus germplasm set was evaluated in greenhouse and field trials for several seedling development, agronomic, and seed quality traits. The traits were highly correlated within the individual trait categories and moderately correlated between the different trait categories. We observed differences in phenotypic diversity among the examined eight germplasm types. The reduction of phenotypic diversity was on average more pronounced for the seedling development traits than for the agronomic and seed quality traits, suggesting that plant breeders need to introgress new genetic variation with respect to the former. PMID- 22782255 TI - Cerebral MRI and EEG studies in the initial management of pediatric headaches. AB - BACKGROUND AND STUDY PURPOSE: High resolution imaging modalities and electroencephalographic studies (EEG) are used in the assessment of children with headaches. We evaluated the role of cerebral MRI (cMRI) and EEG in the initial assessment of children with headache as the chief complaint of initial presentation. METHODS: A retrospective chart analysis was performed at a tertiary University Hospital. RESULTS: 209 patients were included in this study [mean age 11.3 years; male 91 (43.5%); female 118 (56.5%)]. The following types of headaches were seen: Unclassified headache: 23.4%; probable migraine 17.2%, migraine without aura 13.4%, complicated migraine 12.4%, migraine with aura 1.0%; tension-type 15.3%, and cluster headaches 0.5%, and secondary headaches 16.7%. In 93 children (44.5%) abnormal physical/neurological findings were noted (multiple entries possible). On cMRI studies the following findings were seen: Infection of sinuses (7.2%), pineal cysts (2.4%), arachnoidial cyst and Chiari malformation (1.9%), unspecified signal enhancement (1.0%), and pituitary enlargement, inflammatory lesion, angioma, cerebral ischaemia, and intra-cerebral cyst (each 0.5%). Electroencephalographic findings included both focal and generalised abnormal slowing (5.3%) and Spike-wave complexes (3.3%). CONCLUSIONS: Despite abnormal findings on neurological/physical examination in a substantial number of children with headaches, the yield of pathological cMRIs was low. The use of EEG recordings was not contributory to the diagnostic and therapeutic approach. More research is needed to better define those patients who are likely to have an intracranial pathology. PMID- 22782256 TI - Postoperative tooth sensitivity with a new self-adhesive resin cement--a randomized clinical trial. AB - OBJECTIVES: This study evaluated and compared sensitivity of teeth after cementation of full-coverage crowns with a new self-adhesive resin cement (SARC). A resin-modified glass ionomer cement (RMGIC) served as control. MATERIALS AND METHODS: Eighty-eight full-coverage crowns were cemented to vital teeth with either the self-adhesive cement iCem (Heraeus Kulzer; n = 44) or the RMGIC GC Fuji PLUS (GC, n = 44). Before preparations, patients were questioned for sensitivity (patient sensitivity, PS). In addition, air was blown for 2 s onto the buccal cementoenamel junction (air sensitivity, AS), and ice spray was applied in the cementoenamel junction area (ice sensitivity, IS). Patient responses were recorded with a visual analog scale. After cementation of the crowns, patients were recalled for follow-up (f/u) visits at 1 day, 1 week, and 3 weeks. PS, AS, and IS were recorded during each visit. Data were analyzed with Mann-Whitney U tests. RESULTS: The two groups revealed comparable sensitivity scores at baseline. SARC showed significantly lower PS sensitivity scores at 1 day (p = 0.02) and significantly lower AS scores at 1-week follow-up (p = 0.01). IS generally produced the highest sensitivity scores with SARC revealing significantly lower scores at all follow-up visits. CONCLUSION: Cementation of crowns with the SARC tested in this study resulted in overall lower postoperative sensitivity than with the RMGIC. CLINICAL RELEVANCE: Among other clinical advantages, some self-adhesive resin cements seem to lower postoperative sensitivity of crowned teeth. PMID- 22782257 TI - Influence of a mouthwash containing hydroxyapatite microclusters on bacterial adherence in situ. AB - OBJECTIVE: The aim of the present study was to investigate the efficacy of a new preparation in dental prophylaxis containing zinc-carbonate hydroxyapatite microclusters (Biorepair) for oral biofilm management. METHODS AND MATERIALS: Initial biofilm formation was carried out in situ with bovine enamel slabs fixed to individual upper jaw splints worn by six subjects. Rinses with the customary preparation as well as with subfractions (hydroxyapatite microclusters in saline solution; liquid phase without particles) were adopted for 1 min in situ after 1 min of pellicle formation, and the bacterial colonization was recorded after 6 h and 12 h, respectively. Rinses with chlorhexidine served as a reference. The adherent microorganisms were quantified and visualized using DAPI staining and live-dead staining (BacLight). Furthermore, the effects on Streptococcus mutans bacteria were tested in vitro (BacLight). RESULTS: Application of the customary preparation and of the separate components distinctly reduced the initial bacterial colonization of the enamel surface in situ as visualized and quantified with all techniques. After 12 h, 1.3 * 10(7) +/- 2.0 * 10(7) bacteria/cm2 were detected on unrinsed control samples with DAPI staining; 2.4 * 10(6) +/- 3.3 * 10(6) after application of Biorepair (12 h after CHX-rinse; 1.3 * 10(5) +/- 9.2 * 10(4)). Also, pure hydroxyapatite microclusters in saline solution (2.1 * 10(6) +/- 3.0 * 10(6)) as well as the liquid phase without particles (5.1 * 10(5) +/- 3.3 * 10(5)) reduced the amount of adherent bacteria. Furthermore, antimicrobial effects on S. mutans were observed in vitro. CONCLUSION: The preparation is an effective compound for biofilm management in the oral cavity due to antiadherent and antibacterial effects. CLINICAL RELEVANCE: The tested mouthrinse seems to be a reasonable amendment for dental prophylaxis. PMID- 22782258 TI - Prognostic value of histamine H1 receptor expression in oral squamous cell carcinoma. AB - OBJECTIVES: Overexpression of the histamine H1 receptor (H1R) has been described in a variety of tumor models, but experience in oral squamous cell carcinomas (OSCC) is not available. Current adjuvant treatment options for OSCC can be improved by the identification of new targets of therapy. Herein, we evaluated H1R expression in a large patient cohort of OSCC. MATERIALS AND METHODS: H1R immunoexpression was evaluated in 191 cases of OSCC and two OSCC cell lines BICR56 and BICR3. Scanned images were digitally analyzed using ImageJ and the immunomembrane plug-in. The combined score of computer-assisted semiquantitative analysis was correlated with manually counted percentages of tumor cells by Kendall's tau (t) correlation coefficient. Disease-free survival times were estimated using the Kaplan-Meier method and were compared by using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. RESULTS: H1R was rarely expressed in OSCC but significantly related with advanced tumor stages (n = 21/191, mean expression 63.5% of cancer cells in positive tumor samples, 95% confidence interval of the mean 53.5 to 73.6%, p = 0.006). Following univariate analysis, patients with H1R expression showed a significant poorer prognosis (p = 0.0004). Multivariate analysis revealed H1R expression as an independent prognostic factor (p = 0.0164). Expression of H1R in cancer cell lines was confirmed by specific staining of OSCC cell lines BICR56 and BICR3. CONCLUSION: This is the first study focusing on H1R expression showing a significant poorer DFS rate in the H1R+ patient cohort. Based on these data, H1R activation may promote carcinogenesis in OSCC. CLINICAL RELEVANCE: Investigation of H1R regulation and its antagonists shows a clear rationale for future supportive anticancer therapies in OSCCs. PMID- 22782259 TI - Hereditary non-spherocytic hemolytic anemia and severe glucose phosphate isomerase deficiency in an Indian patient homozygous for the L487F mutation in the human GPI gene. AB - Homozygous glucose phosphate isomerase (GPI) deficiency is one of the most important erythroenzymopathies causing hereditary non-spherocytic hemolytic anemia (HNSHA). We report an Indian patient with HNSHA showing 85 % reduction in GPI activity resulting from a homozygous missense replacement g.1459C > T in exon 16, leading to a substitution of the protein residue L487F mutation. This mutation has been detected previously in a compound heterozygous state along with another mutation in a GPI deficient patient elsewhere. To our knowledge, this is the first report of HNSHA associated with GPI deficiency with the homozygous L487F mutation, as well as the first report from India of GPI deficiency. Molecular modeling using the human crystal structure of GPI as a model was performed to determine how this mutation could affect enzyme structure and function. The enzyme is present in a dimeric form necessary for normal activity; the L487F mutation causes a loss of the ability of GPI to dimerize, which decreases the thermostability of the enzyme and results in significant changes in erythrocyte metabolism. PMID- 22782260 TI - Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis. AB - We have demonstrated that adipose tissue-derived mesenchymal stem cells (ADSCs) from mice are capable of reconstituting the hematopoietic microenvironment, and facilitate hematopoiesis more effectively than bone marrow-derived mesenchymal stem cells (BMSCs) in mouse. The ready accessibility of fat tissue rich in MSCs and the higher hematopoiesis-supporting capacities of ADSCs suggest that ADSCs might represent a new therapeutic modality for the regeneration of impaired hematopoiesis. As a further step towards their use in clinical practice, we established human BMSCs and ADSCs from healthy volunteers of similar age, and compared their proliferation capacities, hematopoiesis-supporting properties, and safety. In vitro cell proliferation studies revealed that ADSCs have a higher population doubling number than BMSCs. In vitro co-culture assays showed that ADSCs not only support human CD34(+) peripheral blood stem cells (PBSCs), but also yield significantly more non-adherent hematic cells than BMSCs. In vitro progenitor assays revealed that ADSCs promote a higher frequency of early progenitors than do BMSCs. Interestingly, BM cellularity in irradiated mice that had received ADSCs tended to be higher than that of mice treated with BMSCs. When MSCs were injected into the BM cavity of tibiae, we observed no evidence of MSC induced toxicity either during or after treatment. In addition, no microscopic abnormalities were observed in the bone marrow and major organs. PMID- 22782261 TI - On the contribution of Thomas Clifford Allbutt, F.R.S., to the early history of neuromyelitis optica. AB - The term neuromyelitis optica was coined by Eugene Devic and Fernand Gault in 1894 and refers to the co-occurrence of optic neuritis and myelitis. Neuromyelitis optica (NMO), regarded for many decades as a clinical variant of multiple sclerosis (MS), has only very recently been recognized as a disorder in its own right with distinct pathogenesis, prognosis, and treatment. While the history of classical MS has been extensively studied, only very little is known about the early history of NMO. Here we re-present three forgotten early reports on patients with possible NMO by the later Cambridge Regius Professor of Physic Thomas Clifford Allbutt (1836-1925). To the best of our knowledge, these reports have never been cited before and were also overlooked by Devic and Gault in their seminal review of NMO. One of these reports is likely to correspond to the case briefly mentioned in Allbutt's lecture "On the Ophthalmoscopic Signs of Spinal Disease", published in The Lancet in 1870, which was until very recently considered the first account of NMO in the Western literature. In addition, we discuss the question of Allbutt's primacy in the description of NMO as a syndrome, Allbutt's ideas on the pathogenetic relationship of spinal cord and optic nerve damage, and the reception of those ideas in the medical literature of the nineteenth century. PMID- 22782262 TI - Functional characterisation of vizottin, the first factor Xa inhibitor purified from the leech Haementeria vizottoi. AB - The strategic position of factor Xa (FXa) in blood coagulation makes it a compelling target for the development of new anticoagulants. Blood-sucking animals have in their salivary glands mixtures of anticoagulants, which could be used for designing novel antithrombotic compounds. Herein, we describe Vizottin, the first FXa inhibitor from the salivary complex of the leech Haementeria vizottoi . Vizottin was purified by gel filtration and reverse-phase chromatography, and shown to have anticoagulant effects in human plasma, prolonging the recalcification time in a dose-dependent manner (IC50 40 nM). Vizottin induced blood incoagulability in FX-deficient plasma, whereas in normal and reconstituted plasma, Vizottin doubled the prothrombin time at 160 nM. This peptide competitively inhibited human FXa (K(i) 2 nM) like FXa inhibitors from other leeches, albeit via a distinct mechanism of action. At high concentrations, vizottin inhibited the amidolytic activity of factor VIIa/tissue factor (IC50 96.4 nM). Vizottin inhibited FXa in the prothrombinase complex and Gla-domainless FXa. Moreover, vizottin did not interfere with FX activation induced by RVV-X, a known enzyme that requires the Gla-domain of FX for activation. Competition experiments in the presence of FXa and GGACK-FXa (active site blocked) demonstrated that the inhibition of FXa by vizottin is through binding to the active site rather than an exosite. This novel inhibitor appears to exert its inhibitory effects through direct binding to the active site of FXa in a time dependent manner, but not involving a tight-binding model. In this context, vizottin is a promising model for designing novel anticoagulants for the treatment of thrombotic diseases. PMID- 22782263 TI - From C(sp2)-H to C(sp3)-H: systematic studies on transition metal-catalyzed oxidative C-C formation. AB - In this tutorial review, we will summarize our recent efforts in transition metal catalyzed oxidative coupling via C-H functionalization of aromatic, benzylic and allylic C-H bonds. Related works from other laboratories will be cited where suitable, aiming to give the readers a flavor of this field. Special emphasis is placed on the reaction design and development. PMID- 22782264 TI - Small-scale nuclear extracts for functional assays of gene-expression machineries. AB - A great deal of progress in understanding gene expression has been made using in vitro systems. For most studies, functional assays are carried out using extracts that are prepared in bulk from 10-50 or more liters of cells grown in suspension. However, these large-scale preparations are not amenable to rapidly testing in vitro effects that result from a variety of in vivo cellular treatments or conditions. This journal video article shows a method for preparing functional small-scale nuclear extracts, using HeLa cells as an example. This method is carried out using as few as three 150 mm plates of cells grown as adherent monolayers. To illustrate the efficiency of the small-scale extracts, we show that they are as active as bulk nuclear extracts for coupled RNA Polymerase II transcription/splicing reactions. To demonstrate the utility of the extract protocol, we show that splicing is abolished in extracts prepared from HeLa cells treated with the splicing inhibitor drug E7107. The small-scale protocol should be generally applicable to any process or cell type that can be investigated in vitro using cellular extracts. These include patient cells that are only available in limited quantities or cells exposed to numerous agents such as drugs, DNA damaging agents, RNAi, or transfection, which require the use of small cell populations. In addition, small amounts of freshly grown cells are convenient and/or required for some applications. PMID- 22782265 TI - Cloning and expression of the Aspergillus oryzae glucan 1,3-beta-glucosidase A (exgA) in Pichia pastoris. AB - The glucan 1,3-beta-glucosidase A gene (exgA) from Aspergillus oryzae and fused to the Saccharomyces cerevisiae signal peptide (alpha-factor) was expressed under the control of either a constitutive (GAP) or an inducible (AOX1) promoter in Pichia pastoris. A 1.4-fold higher extracellular enzyme activity (2 U/ml) was obtained using the AOX1 inducible expression system than with the GAP constitutive promoter (1.4 U/ml). The purified recombinant ExgA enzyme, with a yield of 10 mg protein/l culture supernatant, was about 40 kDa by SDS-PAGE analysis with a specific activity of 289 U/mg protein. The enzyme was optimally active at 35 degrees C and pH 5.0 and displayed a K(M) and V(max) of 0.56 mM and 10,042 MUmol/(min mg protein), respectively, with p-nitrophenyl-beta-D glucopyranoside as the substrate. Moreover, it was tolerant to glucose inhibition with a K(i) of 365 mM. PMID- 22782266 TI - In silico analysis of amino acid biosynthesis and proteolysis in Lactobacillus delbrueckii subsp. bulgaricus 2038 and the implications for bovine milk fermentation. AB - The amino acid biosynthesis pathway and proteolytic system of Lactobacillus delbrueckii subsp. bulgaricus 2038 (L. bulgaricus 2038), a mainstay of large scale yogurt production, were modeled based on its genomic sequence. L. bulgaricus 2038 retains more potential for amino acid synthesis and a more powerful proteolytic system than other L. bulgaricus strains, but favors amino acid uptake over de novo synthesis. Free amino acids and peptides in bovine milk provide the main nitrogen sources; whey is more important than casein for L. bulgaricus during fermentation. Free amino acids are imported by amino acid permeases and by ABC-type transport systems whereas exogenous oligopeptides are imported by ABC-type proteins only. Histidine is neither synthesized nor imported singly, which might explain why L. bulgaricus cannot grow in synthetic media. PMID- 22782267 TI - A non-rotational, computer-controlled suspension bioreactor for expansion of umbilical cord blood mononuclear cells. AB - The proliferation and differentiation characteristics of umbilical cord blood mononuclear cells were examined in a non-rotational suspension bioreactor with a fishtail mixer. The system consisted of a glass vessel, a mixer that moved vertically, a data acquisition and control system to continuously monitor pH, temperature and dissolved O(2). The bioreactor provided superior expansion of total HSCs and not total cell number, as well as expression of stemness-related genes which followed with increasing in number of colony-forming cells during 14 days of culture compared to T -lask culture. Vertical agitation thus reduces the total cell number, which may be related to increased shear stress, but has no effect on HSC function. PMID- 22782268 TI - Plasmid size can affect the ability of Escherichia coli to produce high-quality plasmids. AB - Large molecular weight plasmids are often used in gene therapy and DNA vaccines. To investigate the effect of plasmid size on the performance of Escherichia coli host strains during plasmid preparation, we employed E. coli JM109 and TOP10 cells to prepare four plasmids ranging from 4.7 to 16.8 kb in size. Each plasmid was extracted from JM109 and TOP10 cells using an alkaline lysis mini-preparation method. However, when commercial kits were used to extract the same plasmids from JM109 cells, the large molecular weight plasmids substantially degraded, compared with their smaller counterparts. No degradation was observed when the four plasmids were extracted from E. coli TOP10 cells using the same commercial kit. We conclude, therefore, that the performance of E. coli in high quality plasmid preparations can be affected by plasmid size. PMID- 22782269 TI - High-level expression of a xylanase gene from the thermophilic fungus Paecilomyces thermophila in Pichia pastoris. AB - A xylanase gene from Paecilomyces thermophila was functionally expressed in Pichia pastoris. The recombinant xylanase (xynA) was predominantly extracellular; in a 5 l fermentor culture, the total extracellular protein was 8.1 g l(-1) with an activity of 52,940 U ml(-1). The enzyme was purified to homogeneity with a recovery of 48 %. The recombinant xynA was optimally active at 75 degrees C, as measured over 10 min, and at pH 7. The enzyme was stable up to 80 degrees C for 30 min. It hydrolyzed birchwood xylan, beechwood xylan and xylooligosaccharides to produce xylobiose and xylotriose as the main products. PMID- 22782270 TI - Profiling of carotenoids in six microalgae (Eustigmatophyceae) and assessment of their beta-carotene productions in bubble column photobioreactor. AB - The profiles of carotenoids and production of beta-carotene by six eustigmatophytes, Eustigmatos magnus, Eustigmatos polyphem, Eustigmatos vischeri, Vischeria helvetica, Vischeria punctata and Vischeria stellata, grown in a bubble column photobioreactor were measured. All eustigmatophytes contained beta carotene, violaxanthin and vaucheriaxanthin as their major carotenoids and accumulated large amount of beta-carotene, which accounted for over 50 % of total carotenoids. Maximum intracellular beta-carotene contents ranged 1.5-3.5 % of dry wt and in V. stellata it reached 5.9 % dry wt, accompanied by a biomass dry wt >7.3 g/l, with the highest up to 9.8 g/l. These eustigmatophytes are thus promising producers of beta-carotene. PMID- 22782271 TI - Microparticle based morphology engineering of filamentous microorganisms for industrial bio-production. AB - Filamentous microorganisms are important work horses in industrial biotechnology and supply enzymes, antibiotics, pharmaceuticals, bulk and fine chemicals. Here we highlight recent findings on the use of microparticles in the cultivation of filamentous bacteria and fungi, with the aim of enabling a more precise control of their morphology towards better production performance. First examples reveal a broad application range of microparticle based processes, since multiple filamentous organisms are controllable in their growth characteristics and respond by enhanced product formation. PMID- 22782272 TI - Characterization of a recombinant cellobiose 2-epimerase from Dictyoglomus turgidum that epimerizes and isomerizes beta-1,4- and alpha-1,4-gluco oligosaccharides. AB - A recombinant putative N-acyl-D-glucosamine 2-epimerase from Dictyoglomus turgidum was identified as a cellobiose 2-epimerase by evaluating its substrate specificity. The purified enzyme was a 46 kDa monomer with a specific activity of 16.8 MUmol min(-1) mg(-1) for cellobiose. The epimerization activity was maximal at pH 7.0 and 70 degrees C with a half-life of 55 h. The isomerization of the glucose at the reducing end of beta-1,4- and alpha-1,4-linked gluco oligosaccharides to a fructose moiety by the enzyme took place after the epimerization of the glucose to a mannose moiety. The enzyme converted cellobiose to 12.8 % 4-O-beta-D-glucopyranosyl-D-mannose and 54.6 % 4-O-beta-D glucopyranosyl-D-fructose as an equilibrium and converted lactose to 12.8 % epilactose and 54.3 % lactulose. PMID- 22782273 TI - Tracheostomy tube change before day 7 is associated with earlier use of speaking valve and earlier oral intake. AB - BACKGROUND: Presence of a tracheostomy tube often decreases the patient's ability to communicate and to tolerate oral intake. The initial tracheostomy tube change is often recommended between day 7 and 14 post insertion. Local guidelines permit tracheostomy tube change 5 days after insertion. OBJECTIVE: We hypothesized that changing tracheostomy tubes before day 7 is associated with earlier use of a speaking valve as well as earlier oral intake, compared to changing tracheostomy tubes after 7 days. METHODS: We prospectively enrolled 130 admitted subjects, after tracheostomy placement to a respiratory care unit between July 2008 and May 2010. Subject data were recorded from the electronic medical record. The primary end point was the time from tracheostomy tube placement to tolerating speaking valve. The secondary end point was the time from tracheostomy tube placement to tolerating oral intake. Complications of tracheostomy tube change were recorded. RESULTS: Thirty-eight subjects had the first tracheostomy tube change before 7 days (early group), and 92 subjects had the first tracheostomy tube change after 7 days (late group). The early group tolerated a speaking valve significantly sooner than the late group (7 d vs 12 d, P = .001). The early group also tolerated oral intake significantly sooner (10 d vs 20 d, P = .04). After change of the tracheostomy tube, the time to tolerating oral feeding was 5.5 days in both groups. There was no significant difference in time to decannulation between the groups. The early group had a shorter respiratory care unit stay (11 d vs 17 d, P = .001) and a shorter hospital stay (P = .05) than the late group. There was no difference in survival. There were no complications associated with tracheostomy tube change. CONCLUSIONS: Tracheostomy tube change before day 7 is associated with earlier ability to tolerate speaking valve and oral intake. In this series, early tracheostomy tube change was not associated with an increased rate of complications. PMID- 22782274 TI - Predictors of adherence to inhaled medications among Veterans with COPD. AB - BACKGROUND: Factors contributing to medication nonadherence among patients with chronic obstructive pulmonary disease (COPD) are poorly understood. OBJECTIVES: To identify patient characteristics that are predictive of adherence to inhaled medications for COPD and, for patients on multiple inhalers, to assess whether adherence to one medication class was associated with adherence to other medication classes. DESIGN: Cohort study using data from Veteran Affairs (VA) electronic databases. PARTICIPANTS: This study included 2,730 patients who underwent pulmonary function testing between 2003 and 2007 at VA facilities in the Northwestern United States, and who met criteria for COPD. MAIN MEASURES: We used pharmacy records to estimate adherence to inhaled corticosteroids (ICS), ipratropium bromide (IP), and long-acting beta-agonists (LABA) over two consecutive six month periods. We defined patients as adherent if they had refilled medications to have 80 % of drug available over the time period. We also collected information on their demographics, behavioral habits, COPD severity, and comorbidities. KEY RESULTS: Adherence to medications was poor, with 19.8 % adherent to ICS, 30.6 % adherent to LABA, and 25.6 % adherent to IP. Predictors of adherence to inhaled therapies were highly variable and dependent on the medication being examined. In adjusted analysis, being adherent to a medication at baseline was the strongest predictor of future adherence to that same medication [(Odds ratio, 95 % confidence interval) ICS: 4.78 (3.21-7.11); LABA: 6.56 (3.89-11.04); IP: 13.96 (9.88-19.72)], [corrected] but did not reliably predict adherence to other classes of medications. [corrected]. CONCLUSIONS: Among patients with COPD, past adherence to one class of inhaled medication strongly predicted future adherence to the same class of medication, but only weakly predicted adherence to other classes of medication. PMID- 22782275 TI - Improving the informed consent process for research subjects with low literacy: a systematic review. AB - BACKGROUND: Inadequate health literacy may impair research subjects' ability to participate adequately in the informed consent (IC) process. Our aim is to evaluate the evidence supporting interventions, to improve comprehension of the IC process in low literacy subjects. METHODS: We performed a MEDLINE database search (1966 to November 2011) supplemented by manual searches of bibliographies of key relevant articles. We selected all studies in which a modification of the IC was tested to improve comprehension in low literacy populations. Study design, quality criteria, population, interventions and outcomes for each trial were extracted. The main outcome evaluated was comprehension, measured using a written test or verbal comprehension. RESULTS: Our search strategy yielded 281 studies, of which only six met our eligibility criteria. The six studies included 1620 research participants. The studies predominantly included populations that were older (median age 61, range 48-64), ethnic minority, and with literacy level of 8th grade or below. Only one study had a randomized design. The specific intervention differed in each study. Two of the studies included the teach-back method or teach to goal method and achieved the highest level of comprehension. Two studies changed the readability level of the IC and resulted in the lowest comprehension among study subjects. CONCLUSIONS: The evidence supporting interventions to improve the informed consent process in low literacy populations is extremely limited. Among the interventions evaluated, having a study team member spend more time talking one-on-one to study participants was the most effective strategy for improving informed consent understanding; however, this finding is based on the results of a single study. PMID- 22782277 TI - Comorbidities, treatment and survival. PMID- 22782279 TI - Does the moral arc of the universe really bend toward justice? PMID- 22782280 TI - Just because it's low cost doesn't mean it's accessible. PMID- 22782281 TI - Patient-reported quality of pain treatment and use of interpreters in spanish speaking patients hospitalized for obstetric and gynecological care. AB - BACKGROUND: Assessment and treatment of pain are based largely on patient's self reports. Patients with limited English proficiency (LEP) may have difficulties communicating their pain symptoms in the presence of language barriers. OBJECTIVE: To determine whether interpreter use was associated with quality of acute pain treatment among Latina patients with limited English proficiency. DESIGN: Secondary analysis of two cross-sectional surveys. PARTICIPANTS: One hundred and eighty-five Latino female patients hospitalized for obstetric and gynecological care who required interpreter services. Patients were classified into two groups according to interpreter availability ('Always' and 'Not Always' available). MAIN MEASURES: Quality of pain treatment was measured by patient report of 1) overall level of pain control during hospitalization; 2) timeliness of pain treatment; and 3) perceived provider helpfulness to treat pain. KEY RESULTS: Patients who always received interpreters were more likely to report higher levels of pain control (P=0.02), timely pain treatment (P=0.02), and greater perceived provider helpfulness to treat their pain (P=0.005), compared with patients who not always received interpreters. CONCLUSION: Use of interpreters by LEP patients was associated with better patient reports on quality of pain treatment, and may also improve clinical interactions related to pain. PMID- 22782282 TI - Primary care utilization and mental health diagnoses among adult patients requiring interpreters: a retrospective cohort study. AB - BACKGROUND: Patients requiring interpreters may utilize the health care system differently or more frequently than patients not requiring interpreters; those with mental health issues may be particularly difficult to diagnose. OBJECTIVE: To determine whether adult patients requiring interpreters exhibit different health care utilization patterns and rates of mental health diagnoses than their counterparts. DESIGN: Retrospective cohort study examining patient visits to primary care (PC), express care (EC), or the emergency department (ED) of a large group practice within 1 year. PATIENTS: Adult outpatients (n = 63,525) with at least one visit within the study interval and information regarding interpreter need. MAIN MEASURES: Mean visit counts, counts of mental disorders, and somatic symptom diagnoses between patients requiring interpreters (IS patients) and not requiring interpreters (non-IS patients). KEY RESULTS: IS patients (n = 1,566) had a higher mean number of visits overall (3.10 vs. 2.52), in PC (2.54 vs. 1.95), and in ED (0.53 vs. 0.44) than non-IS patients (all p < 0.01). IS patients had a lower mean number of visits in EC than non-IS patients (0.03 vs. 0.13; p < 0.01). Interpreter need remained a significant predictor of visit count in multivariate analyses including age, sex, insurance, and clinical complexity. A greater proportion of IS patients were high utilizers (10+ visits) than non-IS patients (3.6 % vs. 1.7 %; p < 0.01). IS patients had a lower frequency of mental health diagnoses (13.9 % vs. 16.7 %), but a higher frequency of diagnoses recognized as potential somatic symptoms including diseases of the nervous (29.3 % vs. 24.2 %), digestive (22.6 % vs. 14.5 %), and musculoskeletal systems (43.2 % vs. 34.5 %), and ill-defined conditions (61 % vs. 49.9 %), all p < 0.01. CONCLUSIONS: IS patients visited PC more often than their counterparts and were more often high utilizers of care. Two sources of high utilization, mental health diagnoses and somatic symptoms, differed appreciably between our populations and may be contributing factors. PMID- 22782283 TI - Transcranial Doppler monitoring of middle cerebral flow velocity in a patient with a ventriculoperitoneal shunt undergoing laparoscopy. AB - Laparoscopic surgery is possibly associated with a risk of intracranial pressure (ICP) increase due to pneumoperitoneum in patients with ventriculoperitoneal shunts (VPS). Invasive techniques for shunt pressure monitoring are not routinely used because of the possible complications. Transcranial Doppler (TCD) is a non invasive, safe method which gives accurate information about blood-flow velocities in basal cerebral arteries and indirectly about the ICP. Moreover it is inexpensive and simple in use. We report the use of TCD for middle cerebral flow velocity monitoring in a patient with a VPS who underwent laparoscopic surgery. In the case we present, during 60 min of pneumoperitoneum, TCD showed a sustained, but not clinically significant increase of the Pulsatility Index, with a recorded maximum change of 31 %. We consider that the use of TCD may increase the safety of laparoscopic procedures in patients with preexisting VPS. PMID- 22782285 TI - Synthesis and catalytic activity of heterogeneous rare-earth metal catalysts coordinated with multitopic Schiff-base ligands. AB - Four multitopic Schiff-base ligand precursors were synthesized via condensation of 4,4'-diol-3,3'-diformyl-1,1'-diphenyl or 1,3,5-tris(4-hydroxy-5 formylphenyl)benzene with 2,6-diisopropylaniline or 2,6-dimethylaniline. Amine elimination reactions of Ln[N(SiMe(3))(2)](3) (Ln = La, Nd, Sm or Y) with these multitopic ligand precursors gave ten heterogeneous rare-earth metal catalysts. These heterogeneous rare-earth metal catalysts are active for intramolecular hydroalkoxylation of alkynols, and the catalytic activities are influenced by the ligand and metal ion. The recycling experiment on the most active heterogeneous catalyst showed the catalyst has a good reusability. PMID- 22782286 TI - Prevalence of monogenic diabetes amongst Polish children after a nationwide genetic screening campaign. AB - AIMS/HYPOTHESIS: The aim of this study was to study dynamic changes in the prevalence of different types of diabetes in paediatric populations in Poland, with a specific focus on monogenic diabetes (MD). METHODS: Using epidemiologic data (PolPeDiab Collaboration) and nationwide genetic test results (TEAM Programme), we compared the prevalence of type 1, type 2 and cystic fibrosis related diabetes (CFRD) and MD. Genetically confirmed MD included MODY, neonatal diabetes and Wolfram and Alstrom syndromes. The study covered all children aged 0 18 years treated for diabetes between 2005 and 2011 in three regions, inhabited by 23.7% (1,989,988) of Polish children, with a low prevalence of childhood obesity (<5%). RESULTS: The prevalence of type 1 diabetes showed a continuous increase, from 96 to 138/100,000 children. The prevalence of type 2 diabetes and CFRD also increased, from 0.3 to 1.01/100,000 children and from 0.1 to 0.95/100,000 children, respectively. The prevalence of MD was stable at between 4.2 and 4.6/100,000 children, accounting for 3.1-4.2% of children with diabetes, with glucokinase (GCK)-MODY being the most frequent type, amounting to 83% of patients with MD. The percentage of positive test results decreased with the number of referrals, suggesting that children with the highest probability of MD were referred initially, followed by those with a less clear-cut phenotype. The prevalence of neonatal diabetes equalled 1 in 300,000 children. CONCLUSIONS/INTERPRETATION: The prevalence of MD in a paediatric population with a low prevalence of obesity remains stable and is nearly fivefold higher than that of type 2 diabetes and CFRD, justifying a need for increased access to genetic diagnostic procedures in diabetic children. PMID- 22782287 TI - Targeting of mitochondrial reactive oxygen species production does not avert lipid-induced insulin resistance in muscle tissue from mice. AB - AIMS/HYPOTHESIS: High-fat, high-sucrose diet (HF)-induced reactive oxygen species (ROS) levels are implicated in skeletal muscle insulin resistance and mitochondrial dysfunction. Here we investigated whether mitochondrial ROS sequestering can circumvent HF-induced oxidative stress; we also determined the impact of any reduced oxidative stress on muscle insulin sensitivity and mitochondrial function. METHODS: The Skulachev ion (plastoquinonyl decyltriphenylphosphonium) (SkQ), a mitochondria-specific antioxidant, was used to target ROS production in C2C12 muscle cells as well as in HF-fed (16 weeks old) male C57Bl/6 mice, compared with mice on low-fat chow diet (LF) or HF alone. Oxidative stress was measured as protein carbonylation levels. Glucose tolerance tests, glucose uptake assays and insulin-stimulated signalling were determined to assess muscle insulin sensitivity. Mitochondrial function was determined by high resolution respirometry. RESULTS: SkQ treatment reduced oxidative stress in muscle cells (-23% p < 0.05), but did not improve insulin sensitivity and glucose uptake under insulin-resistant conditions. In HF mice, oxidative stress was elevated (56% vs LF p < 0.05), an effect completely blunted by SkQ. However, HF and HF+SkQ mice displayed impaired glucose tolerance (AUC HF up 33%, p < 0.001; HF+SkQ up 22%; p < 0.01 vs LF) and disrupted skeletal muscle insulin signalling. ROS sequestering did not improve mitochondrial function. CONCLUSIONS/INTERPRETATION: SkQ treatment reduced muscle mitochondrial ROS production and prevented HF-induced oxidative stress. Nonetheless, whole-body glucose tolerance, insulin-stimulated glucose uptake, muscle insulin signalling and mitochondrial function were not improved. These results suggest that HF induced oxidative stress is not a prerequisite for the development of muscle insulin resistance. PMID- 22782288 TI - Role of TCF7L2 risk variant and dietary fibre intake on incident type 2 diabetes. AB - AIMS/HYPOTHESIS: The T allele of transcription factor 7-like 2 gene variant, TCF7L2 rs7903146, increases the risk of type 2 diabetes by 40-50%. As TCF7L2 rs7903146 has been associated with diminished incretin effect we investigated whether interaction between dietary intake of carbohydrate, fat, protein or fibre and this variant affects the risk of type 2 diabetes. METHODS: A cohort of 24,799 non-diabetic individuals from the Malmo Diet and Cancer Study (MDCS), with dietary data obtained by a modified diet history method, were followed up for 12 years, with 1,649 recordings of incident type 2 diabetes made. Risk of type 2 diabetes in strata of diet quintiles was analysed prospectively adjusting for potential confounders. Cross-sectional analyses were performed on baseline fasting glucose and HbA(1c) levels in a subset of 5,216 randomly selected individuals from the MDCS. RESULTS: The elevated risk of type 2 diabetes with rs7903146 (OR 1.44, 95% CI 1.33, 1.56, p = 4.6 * 10(-19)) increased with higher intake of dietary fibre (OR 1.24, 95% CI 1.04, 1.47 to OR 1.56, 95% CI 1.31, 1.86 from the lowest to highest quintile; p (interaction) = 0.049). High intake of dietary fibre was inversely associated with diabetes incidence only among CC genotype carriers (OR 0.74, 95% CI 0.58, 0.94 per quintile, p = 0.025). The T allele was associated with 0.027% elevated HbA(1c) (p = 0.02) and this effect increased with higher intake of fibre (from -0.021% to 0.079% for the lowest to the highest quintile, p (interaction) = 0.02). Each quintile of higher fibre intake was associated with lower HbA(1c) levels among CC and CT but not among TT genotype carriers (-0.036%, p = 6.5 * 10(-7); -0.023%, p = 0.009; and 0.012%, p = 0.52, respectively). CONCLUSIONS/INTERPRETATION: Our study suggests that dietary fibre intake may modify the association between TCF7L2 rs7903146 and incidence of type 2 diabetes, and that higher fibre intake may associate with protection from type 2 diabetes only among non-risk allele carriers. PMID- 22782290 TI - Pseudoparalysis of shoulder caused by glenohumeral interposition of rotator cuff tendon stumps: a rare complication of posterior shoulder dislocation. AB - Magnetic resonance imaging (MRI) findings of a rare complication of posterior glenohumeral dislocation are described in two patients which led to shoulder dysfunction caused by interposition of rotator cuff tendon(s) into the glenohumeral joint. Both patients underwent successful surgical fixation and now have returned to normal shoulder function. PMID- 22782289 TI - A genotype risk score predicts type 2 diabetes from young adulthood: the CARDIA study. AB - AIMS/HYPOTHESIS: Genotype does not change over the life course and may thus facilitate earlier identification of individuals at high risk for type 2 diabetes. We hypothesised that a genotype score predicts incident type 2 diabetes from young adulthood and improves diabetes prediction models based on clinical risk factors alone. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study followed young adults (aged 18-30 years, mean age 25) serially into middle adulthood. We used Cox regression to build nested prediction models for incident type 2 diabetes based on clinical risk factors assessed in young adulthood (age, sex, race, parental history of diabetes, BMI, mean arterial pressure, fasting glucose, HDL-cholesterol and triacylglyercol), without and with a 38-variant genotype score. Models were compared with C statistics and continuous net reclassification improvement indices (NRI). RESULTS: Of 2,439 participants, 830 (34%) were black and 249 (10%) had a BMI >= 30 kg/m(2) at baseline. Over a mean 23.9 years of follow-up, 215 (8.8%) participants developed type 2 diabetes. The genotype score significantly predicted incident diabetes in all models, with an HR of 1.08 per risk allele (95% CI 1.04, 1.13) in the full model. The addition of the score to the full model modestly improved reclassification (continuous NRI 0.285; 95% CI 0.126, 0.433) but not discrimination (C statistics 0.824 and 0.829 in full models with and without score). Race-stratified analyses were similar. CONCLUSIONS/INTERPRETATION: Knowledge of genotype predicts type 2 diabetes over 25 years in white and black young adults but may not improve prediction over routine clinical measurements. PMID- 22782291 TI - MRI findings in thoracic outlet syndrome. AB - We discuss MRI findings in patients with thoracic outlet syndrome (TOS). A total of 100 neurovascular bundles were evaluated in the interscalene triangle (IS), costoclavicular (CC), and retropectoralis minor (RPM) spaces. To exclude neurogenic abnormality, MRIs of the cervical spine and brachial plexus (BPL) were obtained in neutral. To exclude compression on neurovascular bundles, sagittal T1W images were obtained vertical to the longitudinal axis of BPL from spinal cord to the medial part of the humerus, in abduction and neutral. To exclude vascular TOS, MR angiography (MRA) and venography (MRV) of the subclavian artery (SA) and vein (SV) in abduction were obtained. If there is compression on the vessels, MRA and MRV of the subclavian vessels were repeated in neutral. Seventy one neurovascular bundles were found to be abnormal: 16 arterial-venous neurogenic, 20 neurogenic, 1 arterial, 15 venous, 8 arterial-venous, 3 arterial neurogenic, and 8 venous-neurogenic TOS. Overall, neurogenic TOS was noted in 69%, venous TOS in 66%, and arterial TOS in 39%. The neurovascular bundle was most commonly compressed in the CC, mostly secondary to position, and very rarely compressed in the RPM. The cause of TOS was congenital bone variations in 36%, congenital fibromuscular anomalies in 11%, and position in 53%. In 5%, there was unilateral brachial plexitis in addition to compression of the neurovascular bundle. Severe cervical spondylosis was noted in 14%, contributing to TOS symptoms. For evaluation of patients with TOS, visualization of the brachial plexus and cervical spine and dynamic evaluation of neurovascular bundles in the cervicothoracobrachial region are mandatory. PMID- 22782292 TI - Changes in adolescents mental health and use of alcohol and tobacco: a 10-year time-trend study of Finnish adolescents. AB - The present study examines the 10-year time-trend changes of adolescent psychiatric symptoms, smoking and alcohol use. Representative population-based samples with same methods at two time-points, same age range and with 10-year period between the time points were gathered in Finland to investigate secular changes in adolescents' emotional and behavioral problems. Seventh and ninth grade students filled in the Strengths and Difficulties Questionnaire (SDQ) and questions regarding alcohol use and smoking anonymously during a school lesson in 1998 (n = 1458) and 2008 (n = 1569). The self-reports of SDQ showed substantial stability in emotional and behavioral problems from 1998 to 2008. There was no increase between the two timepoints in self-reports of SDQ total, conduct, hyperactivity, emotional or peer problems when using the 90th percentile clinical cut-off points. However, there was a trend showing decreasing prosocial behavior among girls indicating that proportions of adolescent boys and girls having problems in prosocial behavior have converged, The self-reported alcohol use, drunkenness and cigarette smoking decreased within the 10-year time period. Of alcohol use, the number of non-users increased from 44 to 63 % between the years 1998 and 2008. Similarly, the proportion of non-smokers increased from 56 to 68 %. Although rates of substance use declined within the 10-year study period, drunkenness-oriented alcohol use and regular smoking are still prevalent among Finnish adolescents. PMID- 22782293 TI - Two-dimensional nanoarchitectonics: organic and hybrid materials. AB - Programmed molecular assemblies with molecular-level precision have always intrigued mankind in the quest to master the art of molecular engineering. In this regard, our review seeks to highlight the state of the art in supramolecular engineering. Herein we describe two-dimensional (2D) nanoarchitectonics of organic and organic-inorganic based hybrid materials. Molecular systems ranging from simpler hydrogen bonding driven bis-acylurea and cyclic dipeptide derivatives to complex peptoids, arylenes, cucurbiturils, biphenyls, organosilicons and organometallics, which involve a delicate interplay of multiple noncovalent interactions are discussed. These specifically chosen examples illustrate the molecular design principles and synthetic protocols to realize 2D nanosheets. The description also emphasizes the wide variety of functional properties and technological implications of these 2D nanomaterials besides an outlook for future progress. PMID- 22782294 TI - Risk of rash with the anti-HER2 dimerization antibody pertuzumab: a meta analysis. AB - Pertuzumab is a novel humanized monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2) dimerization. It was recently approved by the US FDA for use in combination with trastuzumab and docetaxel for patients with HER2 positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Rash is inconsistently reported as a common adverse event in most clinical trials of pertuzumab, at varying incidences. In this study, we have investigated the overall incidence and risk of rash with pertuzumab. Relevant studies were identified from the PubMed database (1966-2012), abstracts presented at the American Society of Clinical Oncology annual conference (2004-2011), and Web of Science database (1998-2012). Eligible studies were prospective phase II-III clinical trials using pertuzumab in cancer patients. Incidence, relative risk (RR), and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Data from a total of 1,726 patients (pertuzumab, n = 1,157; controls, n = 569) with breast, ovarian, and prostate cancers from eight clinical trials were included for analysis. The incidence of all-grade and high-grade rash with pertuzumab were 24.6 % (95 % CI 19.3-30.8 %) and 1.1 % (95 % CI 0.5-2.2 %), respectively. The risk varied with tumor types, as patients with prostate cancer had a lower incidence of rash (13.2 %; 95 % CI 8.0 21.1 %) than those with breast, ovarian, fallopian tube, and peritoneal cancer (P = 0.001). Overall, pertuzumab significantly increased the risk of rash in comparison with controls (RR 1.53; 95 % CI 1.12-2.09; P = 0.007). Pertuzumab is associated with a significant risk of rash, and the incidence varies among different tumor types. Prevention, early recognition, and appropriate treatment of this rash may lead to improvement in patient quality of life, adherence to therapy, and possibly optimize clinical outcomes. PMID- 22782296 TI - Intrinsic spatial resolution evaluation of the X'tal cube PET detector based on a 3D crystal block segmented by laser processing. AB - The X'tal cube is a depth-of-interaction (DOI)-PET detector which is aimed at obtaining isotropic resolution by effective readout of scintillation photons from the six sides of a crystal block. The X'tal cube is composed of the 3D crystal block with isotropic resolution and arrays of multi-pixel photon counters (MPPCs). In this study, to fabricate the 3D crystal block efficiently and precisely, we applied a sub-surface laser engraving (SSLE) technique to a monolithic crystal block instead of gluing segmented small crystals. The SSLE technique provided micro-crack walls which carve a groove into a monolithic scintillator block. Using the fabricated X'tal cube, we evaluated its intrinsic spatial resolution to show a proof of concept of isotropic resolution. The 3D grids of 2 mm pitch were fabricated into an 18 * 18 * 18 mm(3) monolithic lutetium yttrium orthosilicate (LYSO) crystal by the SSLE technique. 4 * 4 MPPCs were optically coupled to each surface of the crystal block. The X'tal cube was uniformly irradiated by (22)Na gamma rays, and all of the 3D grids on the 3D position histogram were separated clearly by an Anger-type calculation from the 96-channel MPPC signals. Response functions of the X'tal cube were measured by scanning with a (22)Na point source. The gamma-ray beam with a 1.0 mm slit was scanned in 0.25 mm steps by positioning of the X'tal cube at vertical and 45 degrees incident angles. The average FWHM resolution at both incident angles was 2.1 mm. Therefore, we confirmed the isotropic spatial resolution performance of the X'tal cube. PMID- 22782297 TI - New direct oral anticoagulants--current therapeutic options and treatment recommendations for bleeding complications. AB - To date, clinical studies show that the incidence of spontaneous bleeding with new direct oral anticoagulants (DOAs) is comparable to that of established anticoagulants. However, unlike vitamin K antagonists, there are currently no clinically available antidotes or approved reversal agents for new DOAs. Restoring normal coagulation is important in many cases, such as emergency surgeries, serious bleedings, or anticoagulant overdosing. Attempts have been made to restore normal coagulation after treatment with new DOAs using compounds such as recombinant activated factor VII (rFVIIa), prothrombin complex concentrate (PCC), or FEIBA (factor eight inhibitor bypassing activity). Limited pre-clinical data and even less clinical evidence are available on the usefulness of these methods in restoring normal coagulation for the emergency management of critical bleeding episodes. Evaluating the utility of DOAs is further complicated by the fact that it is unknown how predictive established test systems are of the bleeding risks. Clinical practice requires further evaluation of the emergency management options for the new DOAs to define the agents and the doses that are most useful. Furthermore, patients receiving long-term treatment with a DOA are likely to undergo elective surgery at some point, and there is lack of evidence regarding perioperative treatment regimens under such conditions. This review summarises potential bleeding management options and available data on the new DOAs. PMID- 22782298 TI - [Mentoring: support programs for female doctors]. PMID- 22782299 TI - Orthotopic liver transplantation in rats. AB - Clinical progress in the field of liver transplantation has been largely supported by animal models(1,2). Since the publication of the first orthotopic rat liver transplantation in 1979 by Kamada et al.(3), this model has remained the gold standard despite various proposed alternative techniques(4). Nevertheless, its broader use is limited by its steep learning curve(5). In this video paper, we show a simple and easy-to-establish revision of Kamada's two cuff technique. The suprahepatic vena cava anastomosis is performed manually with a running suture, and the vena porta and infrahepatic vena cava anastomoses are performed utilizing a quick-linker cuff system(6). Manufacturing the quick-linker kit is shown in a separate video paper. PMID- 22782300 TI - Efficient sex pheromone trapping: catching the sweetpotato weevil, Cylas formicarius. AB - The sweetpotato weevil, Cylas formicarius (Fabricius) (Coleoptera: Brentidae), is the most serious pest of sweetpotato around the world, damaging sweetpotatoes in the field and in storage, as well as being a quarantine pest. Because the larval period is spent within vines or tubers, and the adults are nocturnal, chemical control frequently is not effective. In addition, there are few natural enemies, and pheromone-based trapping does not appear to reduce the damage level. In the present study, we evaluated a number of parameters that affect pheromone-based trap catch, including trap design, trap size, trap color, and height at which the traps are placed. Pherocon unitraps caught higher numbers than ground, funnel water, or delta traps. Medium-sized traps (13 * 17.5 cm) were more effective than larger or smaller traps. In a color-choice test, C. formicarius preferred red over gray, brown, blue, white, yellow, black, or red traps; light red was more attractive than other shades of red. Maximum catches were obtained when the traps were set 50 cm above the crop canopy. Light-red unitraps with pheromone lures caught more adults than identical traps without lures, suggesting that C. formicarius is influenced by both visual and olfactory cues. Pheromone-baited light-red unitraps, 13 * 17.5 cm, installed 50 cm above the crop canopy, were the most effective at catching C. formicarius adults, and they appear to have the greatest potential for use in trap-and-kill strategies and eradication programs. PMID- 22782301 TI - Chemosensitivity of conjunctival melanoma cell lines to target-specific chemotherapeutic agents. AB - OBJECTIVE: In conjunctival melanoma, local chemotherapy has been based so far on clinical evidence and limited to the therapy of melanoma in situ. Our aim was to define substances that may have the potential to add to therapeutic options in extended local growth and metastatic disease. Two conjunctival cell lines (CRMM-1 and CRMM-2) have been established from recurrent conjunctival melanoma. In this study, we examined the chemosensitivity of these cell lines to different cytotoxic substances. MATERIALS AND METHODS: The cell lines CRMM-1 and CRMM-2 were exposed to chemotherapeutics for 24 h and the IC50 was generated. Sulforhodamin-B assays were used for quantification of in vitro efficacy. Time of exposure and escalating concentrations of the substances were adapted to the experimental setting. RESULTS: Bortezomib, clusianone 502 (nemorosone), ranpirnase, and sorafenib were efficient in inhibiting the growth of conjunctival melanoma cell lines. The IC50 achieved concentrations below or around 10 MUM for these substances. CONCLUSIONS: Bortezomib, clusianone 502, ranpirnase, and sorafenib inhibited growth in conjunctival melanoma cell lines efficiently. The new substances may be a suitable alternative for local therapy. New therapeutic options with highly specific targeted agents for metastatic disease have to be evaluated in further experiments. PMID- 22782302 TI - Psychosocial distress of part-time occlusion in children with intermittent exotropia. AB - PURPOSE: To evaluate the psychosocial distress of part-time occlusion therapy in intermittent exotropia. METHODS: A total of 25 children (15 males and 10 females, aged 3 to 7 years, mean age 4.7 years) with intermittent exotropia were enrolled. Behavioral and psychosocial problems were assessed by the Korean Child Behavior Checklist (K-CBCL), which consists of eight categories of withdrawal, somatic problems, depression/anxiety, social problems, thought problems, attention problems, delinquent behavior, and aggressive behavior, and the Amblyopia Treatment Index (ATI). The ATI was designed to evaluate the three factors of compliance, adverse effect, and social stigma. The Parenting Stress Index (PSI) is a parent self-report designed to identify potentially dysfunctional parent child systems. The K-CBCL was obtained before and after occlusion therapy, and the ATI and PSI were taken from parents only after occlusion therapy. We evaluated the change on the K-CBCL and the correlation between the K-CBCL and ATI. RESULTS: The attention problem assessed by the K-CBCL significantly decreased after occlusion therapy. On the ATI, the social stigma was relatively lower than compliance and adverse effect factors (Likert scale 2.64, 3.11, and 3.11, respectively). The somatic problem assessed by the K-CBCL and compliance on the ATI were significantly correlated (p = 0.014). There was no significant change in percentile scores of each subscale (parental dominant scale and child dominant scale) of the PSI. Total stress index before and after occlusion therapy was 97.16 +/- 8.38 and 97.00 +/- 8.16 respectively (p = 0.382). CONCLUSIONS: Occlusion therapy may influence the psychosocial impact on intermittent exotropia patients. Part-time occlusion significantly decreased the attention problem in children with intermittent strabismus. Children with a high somatic problem score on the KCBCL showed poor compliance to the part-time occlusion. PMID- 22782303 TI - Synthesis and structure of Bi2Ce2O7: a new compound exhibiting high solar photocatalytic activity. AB - A facile method of solution combustion was used to synthesize a new solid solution Bi(2)Ce(2)O(7). The structure was determined from powder X-ray diffraction (PXRD) and found to crystallize in the space group Fm3m with cell parameter a = 5.46936(9) A. The particle sizes varied from 5 to 6 nm. The degradation of cationic dye malachite green (MG) was investigated under solar radiation as the band gap of the material is 2.34 eV. PMID- 22782295 TI - Development and assessment of a composite score for memory in the Alzheimer's Disease Neuroimaging Initiative (ADNI). AB - We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer's Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score. PMID- 22782305 TI - False positive rate of carbon monoxide saturation by pulse oximetry of emergency department patients. AB - BACKGROUND: Symptoms of carbon monoxide (CO) poisoning are non-specific. Diagnosis requires suspicion of exposure, confirmed by measuring ambient CO levels or carboxyhemoglobin (COHb). An FDA-approved pulse oximeter (Rad-57) can measure CO saturation (S(pCO)). The device accuracy has implications for clinical decision-making. METHODS: From April 1 to August 15, 2008, study personnel measured S(pCO) and documented demographic factors at time of clinical blood draw, in a convenience sample of 1,363 subjects presenting to the emergency department at Intermountain Medical Center, Murray, Utah. The technician then assayed COHb. COHb and S(pCO) values were compared by subject; false positive or negative values were defined as S(pCO) at least 3 percentage points greater or less than COHb level, reported by the manufacturer to be +/- 1 SD in performance. RESULTS: In 1,363 subjects, 613 (45%) were male, 1,141 (84%) were light-skinned, 14 in shock, 4 with CO poisoning, and 122 (9%) met the criteria for a false positive value (range 3-19 percentage points), while 247 (18%) met the criteria for a false negative value (-13 to -3 percentage points). Risks for a false positive S(pCO) reading included being female and having a lower perfusion index. Methemoglobin, body temperature, and blood pressure also appear to influence the S(pCO) accuracy. There was variability among monitors, possibly related to technician technique, as rotation of monitors among technicians was not enforced. CONCLUSIONS: While the Rad-57 pulse oximeter functioned within the manufacturer's specifications, clinicians using the Rad-57 should expect some S(pCO) readings to be significantly higher or lower than COHb measurements, and should not use S(pCO) to direct triage or patient management. An elevated S(pCO) could broaden the diagnosis of CO poisoning in patients with non-specific symptoms. However, a negative S(pCO) level in patients suspected of having CO poisoning should never rule out CO poisoning, and should always be confirmed by COHb. PMID- 22782306 TI - Functionalization and post-functionalization: a step towards polyoxometalate based materials. AB - Polyoxometalates (POMs) have remarkable properties and a great deal of potential to meet contemporary societal demands regarding health, environment, energy and information technologies. However, implementation of POMs in various functional architectures, devices or materials requires a processing step. Most developments have considered the exchange of POM counterions in an electrostatically driven approach: immobilization of POMs on electrodes and other surfaces including oxides, embedding in polymers, incorporation into Layer-by-Layer assemblies or Langmuir-Blodgett films and hierarchical self-assembly of surfactant-encapsulated POMs have thus been thoroughly investigated. Meanwhile, the field of organic inorganic POM hybrids has expanded and offers the opportunity to explore the covalent approach for the organization or immobilization of POMs. In this critical review, we focus on the use of POM hybrids in selected fields of applications such as catalysis, energy conversion and molecular nanosciences and we endeavor to discuss the impact of the covalent approach compared to the electrostatic one. The synthesis of organic-inorganic POM hybrids starting from bare POMs, that is the direct functionalization of POMs, is well documented and reliable and efficient synthetic procedures are available. However, as the complexity of the targeted functional system increases a multi-step strategy relying on the post-functionalization of preformed hybrid POM platforms could prove more appealing. In the second part of this review, we thus survey the synthetic methodologies of post-functionalization of POMs and critically discuss the opportunities it offers compared to direct functionalization. PMID- 22782307 TI - Introduction: Nipah virus--discovery and origin. AB - Until the Nipah outbreak in Malaysia in 1999, knowledge of human infections with the henipaviruses was limited to the small number of cases associated with the emergence of Hendra virus in Australia in 1994. The Nipah outbreak in Malaysia alerted the global public health community to the severe pathogenic potential and widespread distribution of these unique paramyxoviruses. This chapter briefly describes the initial discovery of Nipah virus and the challenges encountered during the initial identification and characterisation of the aetiological agent responsible for the outbreak of febrile encephalitis. The initial attempts to isolate Nipah virus from the bat reservoir host are also described. PMID- 22782308 TI - Potentially traumatic event exposure, posttraumatic stress disorder, and Axis I and II comorbidity in a population-based study of Norwegian young adults. AB - PURPOSE: Epidemiologic research on traumatic stress is limited in Norway. Prevalence and correlates of exposure to potentially traumatic events (PTEs) and posttraumatic stress disorder (PTSD), and patterns of comorbidity with DSM-IV Axis I and II disorders were examined in an epidemiologic sample. METHODS: Demographics, PTEs and resulting PTSD, and comorbid DSM-IV diagnoses were assessed in 2,794 members of the Norwegian Institute of Public Health Twin Panel. The sample comprised 37% male, with an average age of 28.2 years (SD = 3.9). RESULTS: Approximately, one-quarter of participants had lifetime PTE exposure; most PTEs were more common in men than in women. Lifetime prevalence of PTSD was 2.6%, and was significantly more common in women than men. Being female and type of PTE (both interpersonal and accidental traumatic events) were associated with increased PTSD symptoms, whereas higher education was associated with lower symptoms. PTSD was related to increased odds of most Axis I and II conditions. CONCLUSIONS: PTE exposure and PTSD prevalence were lower than in the USA, but comparable to other European countries. Sex differences replicated previous research. The relationship between PTSD and borderline personality disorder was significantly stronger than the relationship between PTSD and any other Axis II conditions. PMID- 22782309 TI - Surface engineering of gold nanoparticles for in vitro siRNA delivery. AB - Cellular uptake, endosomal/lysosomal escape, and the effective dissociation from the carrier are a series of hurdles for specific genes to be delivered both in vitro and in vivo. To construct siRNA delivery systems, poly(allylamine hydrochloride) (PAH) and siRNA were alternately assembled on the surface of 11.8 +/- 0.9 nm Au nanoparticles (GNP), stabilized by denatured bovine serum albumin, by the ionic layer-by-layer (LbL) self-assembly method. By manipulating the outmost PAH layer, GNP-PAH vectors with different surface electric potentials were prepared. Then, the surface potential-dependent cytotoxicity of the resultant GNP-PAH particles was evaluated via sulforhodamine B (SRB) assay, while the surface potential-dependent cellular uptake efficiency was quantitatively analyzed by using the flow cytometry method based on carboxyfluorescein (FAM) labeled siRNA. It was revealed that the GNP-PAH particles with surface potential of +25 mV exhibited the optimal cellular uptake efficiency and cytotoxicity for human breast cancer MCF-7 cells. Following these results, two more positively charged polyelectrolytes with different protonating abilities in comparison with PAH, i.e., polyethylenimine (PEI), and poly(diallyl dimethyl ammonium chloride) (PDDA), were chosen to fabricate similarly structured vectors. Confocal fluorescence microscopy studies indicated that siRNA delivered by GNP-PAH and GNP PEI systems was better released than that delivered by the GNP-PDDA system. Further flow cytometric assays based on immunofluorescence staining of the epidermal growth factor receptor (EGFR) revealed that EGFR siRNA delivered by GNP PAH and GNP-PEI exhibited similar down-regulation effects on EGFR expression in MCF-7 cells. The following dual fluorescence flow cytometry assays by co-staining phosphatidylserine and DNA suggested the EGFR siRNA delivered by GNP-PAH exhibited an improved silencing effect in comparison with that delivered by the commercial transfection reagent Lipofectamine 2000. PMID- 22782310 TI - Prognostic value of automated SPECT scoring system for coronary artery disease in stress myocardial perfusion and fatty acid metabolism imaging. AB - Quantitative SPECT analysis contributes to the diagnostic and prognostic assessment of coronary artery disease. A novel automated scoring system (heart score view) can provide identical quantitative information to that determined by expert visual analysis. The aim of the present study is to evaluate the prognostic value of the automated SPECT scoring system when applied to stress thallium and resting beta-methyl-iodophenyl pentadecanoic acid (BMIPP) SPECT images. After a preliminary validation of the automated system by comparison with expert visual analyses, outcome data from 151 consecutive patients with suspected or known coronary artery disease without prior myocardial infarction were analyzed using automated SPECT scores on stress thallium and resting BMIPP images. The software quantified abnormalities as summed stress (SSS), summed rest and summed difference scores for stress thallium and as summed BMIPP scores (SBS). Cardiac events occurred over a period of 48 months in 29 (19.2%) patients with diabetes mellitus, a lower left ventricular ejection fraction (LVEF) and more abnormal scores for thallium and BMIPP. Multivariate predictors of all cardiac events included diabetes mellitus and thallium SSS. The global Chi-square value was significantly increased when SSS was added to the clinical information (diabetes mellitus and LVEF). Negative predictive values of thallium SSS and SBS were almost identical at 84% for all cardiac events and 98% for hard cardiac events. Automatically quantified perfusion and BMIPP scores are related to cardiac events and these values can improve the risk stratification of coronary patients particularly when stress thallium imaging is combined with clinical information. PMID- 22782311 TI - Perceived stress predicts the stability of vitamin K-antagonist treatment of anticoagulant clinic patients. PMID- 22782312 TI - Tumor response assessment to treatment with [177Lu-DOTA0,Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors: differential response of bone versus soft-tissue lesions. AB - We have noted that bone lesions on CT respond differently from soft-tissue lesions to treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu octreotate). We therefore compared the response of bone lesions with that of soft tissue lesions to treatment with (177)Lu-octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors (NETs). METHODS: Forty two patients with well-differentiated NETs who had bone metastases that were positive on [(111)In-DTPA(0)]octreotide somatostatin receptor scintigraphy (SRS) before treatment, and who had soft-tissue lesions, were studied. All patients had had a minimum of 1 follow-up CT scan. Lesions were scored on CT and bone lesions also on SRS before and after treatment. Tumor markers (chromogranin A and 5 hydroxyindoleacetic acid) before and after treatment were compared. RESULTS: Because bone lesions were not visible on CT before treatment in 11 of 42 patients (26%), bone and soft-tissue lesions were evaluated in 31 patients. Whereas bone lesions increased in size, soft-tissue lesions decreased in size. The percentage change in bone and soft-tissue lesions was significantly different at all time points up to 12 mo of follow-up (P < 0.001). The intensity or number of bone lesions on SRS decreased after treatment in 19 of 23 patients (83%) in whom SRS after treatment was available. The tumor markers also decreased significantly after treatment. In 1 patient, bone lesions became visible on CT after treatment, mimicking progressive disease with "new" bone lesions, although there was an overall treatment response. CONCLUSION: In patients with NETs, the apparent increase in size of bone lesions or the appearance of new bone lesions on CT after treatment with (177)Lu-octreotate should be interpreted cautiously, as this finding may be therapy-related rather than indicative of tumor progression. PMID- 22782313 TI - Oncologic PET/MRI, part 2: bone tumors, soft-tissue tumors, melanoma, and lymphoma. AB - With integrated whole-body PET/MRI, a novel metabolic-anatomic imaging technique recently has been introduced into clinical practice. This review addresses PET/MRI of bone tumors, soft-tissue sarcoma, melanoma, and lymphoma. If PET/MRI literature is not yet available for some types of tumors, potential indications are based on available PET/CT and MRI data. PET/MRI seems to be of benefit in T staging of primary bone tumors and soft-tissue sarcomas. With regard to N staging, PET/MRI can be considered similarly accurate to PET/CT when applied as a whole-body staging approach. M-staging will benefit from MRI accuracy in the brain, the liver, and bone. PMID- 22782314 TI - PET of serotonin 1A receptors and cerebral glucose metabolism for temporal lobectomy. AB - The objective of this study was to compare 5-hydroxytryptamine receptor 1A (5 HT(1A)) PET with cerebral metabolic rate of glucose (CMRglc) PET for temporal lobectomy planning. METHODS: We estimated 5-HT(1A) receptor binding preoperatively with (18)F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl) piperazin-1 yl]ethyl-N-(2-pyridyl) cyclohexane carboxamide ((18)F-FCWAY) PET and CMRglc measurement with (18)F-FDG in regions drawn on coregistered MRI after partial volume correction in 41 patients who had anterior temporal lobectomy with at least a 1-y follow-up. Surgery was tailored to individual preresection evaluations and intraoperative electrocorticography. Mean regional asymmetry values and the number of regions with asymmetry exceeding 2 SDs in 16 healthy volunteers were compared between seizure-free and non-seizure-free patients. (18)F-FCWAY but not (18)F-FDG and MRI data were masked for surgical decisions and outcome assessment. RESULTS: Twenty-six of 41 (63%) patients seizure-free since surgery had significantly different mesial temporal asymmetries, compared with 15 non-seizure-free patients for both (18)F-FCWAY (F(1,39) = 5.87; P = 0.02) and (18)F-FDG PET (F(1,38) = 5.79; P = 0.021). The probability of being seizure-free was explained by both (18)F-FDG and (18)F-FCWAY PET, but not MRI, with a significant additional (18)F-FCWAY effect (chi(2)(2) = 9.8796; P = 0.0072) after the probability of being seizure-free was explained by (18)F-FDG. Although MRI alone was not predictive, any combination of 2 lateralizing imaging studies was highly predictive of seizure freedom. CONCLUSION: Our study provides class III evidence that both 5-HT(1A) receptor PET and CMRglc PET can contribute to temporal lobectomy planning. Additional studies should explore the potential for temporal lobectomy based on interictal electroencephalography and minimally invasive imaging studies. PMID- 22782315 TI - Clinical PET of neuroendocrine tumors using 64Cu-DOTATATE: first-in-humans study. AB - The use of positron emitter-labeled compounds for somatostatin receptor imaging (SRI) has become attractive because of the prospect of improved spatial resolution, accelerated imaging procedures, and the ability to quantify tissue radioactivity concentrations. This paper provides results from first-in-humans use of (64)Cu-DOTATATE, an avidly binding somatostatin receptor ligand linked to a radioisotope with intermediate half-life and favorable positron energy (half life, 12.7 h; maximum positron energy, 0.653 MeV). METHODS: In a prospective setup, 14 patients with a history of neuroendocrine tumors underwent both PET/CT with (64)Cu-DOTATATE and SPECT/CT with our current routine imaging agent (111)In diethylenetriaminepentaacetic acid-octreotide. After intravenous injection of 193 232 MBq of (64)Cu-DOTATATE, whole-body PET scans were acquired at 1 h (n = 14), 3 h (n = 12), and 24 h (n = 5) after administration. Tissue radioactivity concentrations for normal organs and lesions were quantified, and standardized uptake values were calculated for the early (1 h) and delayed (3 h) scans. Using the data for 5 patients, we assessed the radiation dose with OLINDA/EXM software. Furthermore, the clinical performance of (64)Cu-DOTATATE with respect to lesion detection was compared with conventional SRI. RESULTS: SRI with (64)Cu-DOTATATE produced images of excellent quality and high spatial resolution. Images were characterized by high and stable tumor-to-background ratios over an imaging time window of at least 3 h. Compared with conventional scintigraphy, (64)Cu-DOTATATE PET identified additional lesions in 6 of 14 patients (43%). In 5 patients, lesions were localized in organs and organ systems not previously known as metastatic sites, including the early-stage detection of a secondary neuroendocrine tumor in a patient with a known mutation in the multiple endocrine neoplasia type I gene. All major additional findings seen only on PET could be confirmed on the basis of a clinical follow-up interval of 18 mo. Calculated radiation dose estimates yielded an effective dose of 6.3 mSv for an injected activity of 200 MBq of (64)Cu-DOTATATE, with the liver being the organ with the highest absorbed radiation dose (0.16 mGy/MBq). CONCLUSION: This first-in-humans study supports the clinical use of (64)Cu-DOTATATE for SRI with excellent imaging quality, reduced radiation burden, and increased lesion detection rate when compared with (111)In-diethylenetriaminepentaacetic acid-octreotide. PMID- 22782316 TI - Pancreaticobiliary disorders: comparison between magnetic resonance cholangiopancreatography images before and after fentanyl injection. AB - OBJECTIVE: This study was designed to determine the effects of intravenous fentanyl on magnetic resonance cholangiopancreatography image quality in the treatment of pancreaticobiliary disorders. MATERIALS AND METHODS: Forty consecutive patients referred for the evaluation of pancreaticobiliary disorders underwent magnetic resonance cholangiopancreatography in the coronal and oblique coronal planes before and after fentanyl injection (every 2 up to 9 min). The images were analyzed qualitatively and quantitatively. Diameter and signal intensity were measured at the widest point and distal to the common bile duct and main pancreatic duct. RESULTS: The mean common bile duct diameters at the widest and distal points and mean pancreatic duct diameter were measured 7.53, 4.72, and 2.14 and 8.33, 5.35, and 2.57 before and after fentanyl injection, respectively. Mean signal intensity at the widest and distal point of the common bile duct and mean pancreatic duct signal intensity measured 278, 199, and 113 and 296, 218, and 121 before and after fentanyl injection, respectively. Minor improvements in image quality were detected qualitatively. CONCLUSION: Fentanyl injection improves images qualitatively and quantitatively. In agreement with previous studies, our results confirm the beneficial effects of fentanyl as a simple adjunct to traditional magnetic resonance cholangiopancreatography. PMID- 22782317 TI - Segmental multicystic dysplastic kidney in an adult: usefulness of enhanced CT in excretory phase. AB - We present an adult case of segmental multicystic dysplastic kidney (SMCDK). The patient had a 10 * 6 cm oval-shaped mass consisting of a solid and multilocular cystic component at the right upper renal sinus. The solid component showed gradual and mild enhancement on dual-phase enhanced CT. Excretory-phase CT demonstrated the excretion of contrast medium into the septa and cysts. Dilation of the upper calices and renal pelvis and atretic renal pelvis in the mass were also clearly visualized in the excretory phase. The signal intensity of the solid component was slightly lower than that of the renal parenchyma on T2-weighted images and similar to that of the medulla on diffusion-weighted images. Right nephrectomy showed a multilocular cystic component within the renal sinus and some of the cysts contained blood. The renal pelvis of the upper moiety was blind, as suggested by CT. Microscopically, there were multiple non-communicating small cysts, as shown by CT, and the wall was lined with immature tubule-like cells. In addition, immature tubule-like cells were seen in the septa. Immature mesenchymal cells were seen around the cysts. The solid component mainly consisted of fibroconnective tissue with immature tubule-like cells. The pathological diagnosis was confirmed as SMCDK. Excretion of contrast media into the septum and cystic component might be a characteristic finding of SMCDK in addition to the finding of a multilocular cystic mass in the upper moiety with urinary tract abnormality. PMID- 22782320 TI - Evolving duodenal atresia in a toddler. PMID- 22782321 TI - Recurrent tracheoesophageal fistula and respiratory failure: the role of early airway endoscopic approach. PMID- 22782322 TI - Cystoscopic removal of leeches in the lower urinary tract: our experience. AB - INTRODUCTION: The purpose of this study is to describe the experience of managing leech infestation in lower urinary tract from a tropical country. MATERIALS AND METHODS: Medical records (January 2002 to December 2010) of children with history of leech infestation in the urinary system, admitted in the Department of Pediatric Surgery, Chittagong Medical College & Hospital, Chittagong, Bangladesh were reviewed. All patients underwent saline irrigation through urethral catheter. When saline irrigation failed, cystoscopic examination was done with removal of leeches by flexible graspers. Follow-up was done 2 weeks later. RESULT: The study included 117 patients. Age ranged from 4 to 12 years. Male and female ratio was 3.7:1. All patients had per urethral bleeding. 51 (43.6%) patients had suprapubic pain. All children underwent saline irrigation through urethral catheter. Spontaneous expulsion occurred after saline irrigation in 57 (48.7%) patients. The expelled leeches were alive in 11 cases; dead in 46 patients. Cystoscopic removal of leeches was done in 60 patients (51.3%). In the cystoscopic group, 54 of the removed leeches were dead and 6 were alive. CONCLUSION: Cystoscopic removal can be a useful technique for the removal of leeches from the urinary tract when saline irrigation fails. PMID- 22782323 TI - Long-term results in scalp tissue expansion in children. AB - INTRODUCTION: Tissue expansion is frequently used in scalp repair in children. The short-term complications are well known and described in the literature. Impacts at a distance such as potential deformation of the skull or widening of the scar are not so often presented. The aim of this study is to analyze the results at a distance and the actual impact after scalp tissue expansion in young children. MATERIALS AND METHODS: We clinically reviewed 15 children operated on between May 2002 and April 2008 for scalp tissue expansion.Results Mean follow-up was 3 years and 5 months, and mean age of the patients at the first surgery was 20 months. In 11 cases, we observed a widening of the scar. Only two patients presented with a slight flattening of the skull. All parents were satisfied with the results. Children do not remind or keep no unpleasant memory of the surgical protocol. DISCUSSION: Only rare studies focused on very young children. Most of surgeons fear about the consequences of scalp tissue expansion on cranial bone and thus on cerebral growth in children under the age of 2. But it appears that cranial changes in young children are transient with a return to normal within 6 months after removing the implant. Another common problem is the scar enlargement. According to our results and the review of the literature, it seems essential to perform the suture in two layers associated to local reconstruction on the scar to provide the best cosmetic outcomes. CONCLUSION: Tissue expansion remains a good technique to repair large lesions of the scalp in children. The deformation of the skull spontaneously resolves and does not have any consequence on brain growth. The widening of the scar is a common problem in children but can be reduced by suture in two layers associated with local reconstruction. Moreover, young children do not keep any unpleasant memory of this period and are not susceptible to social pressure. PMID- 22782324 TI - Effect of VEGF on angiogenesis in pedicle penile skin flaps: an experimental study of urethral reconstruction in rabbits. AB - INTRODUCTION: The aim of this study was to investigate the expression of vascular endothelial growth factor (VEGF) in pedicle penile skin flaps (PPSFs) used for urethral reconstruction in rabbits and the effect of exogenous VEGF on the angiogenesis process in the PPSFs. METHODS: We randomly divided 28 male New Zealand rabbits into two sets of animals. A ventral urethral defect was created in all animals. In the first set of animals (first experiment, n = 10), a PPSF was used for the repair and VEGF expression in the flap was estimated on days 1, 2, 3, 5, and 7 postoperatively. The second set of animals (second experiment, n = 18) included three groups: control, untreated, and VEGF groups. In control group (n = 6), the defect was repaired by simple closure. In untreated (n = 6) and VEGF (n = 6) groups, a PPSF was used for the reconstruction. In VEGF group, exogenous VEGF was injected subdermally on the postoperative day corresponding to the peak endogenous VEGF expression (first experiment results). The animals were sacrificed on the 21st postoperative day and the angiogenic activity was assessed. A p < 0.05 was considered statistically significant. RESULTS: The highest expression of endogenous VEGF in PPSFs was noted on postoperative day 3. Angiogenesis in control, untreated, and VEGF groups was 23.06 +/- 4.1, 30.00 +/- 6.9, and 34.7 +/- 6.9 (mean values +/- standard deviation) vessels per optical field, respectively. There were statistically significant differences between control-untreated groups (p = 0.04) and untreated-VEGF groups (p < 0.0001), and indicative difference between untreated and VEGF groups (p = 0.064). CONCLUSIONS: VEGF is expressed in PPSFs, used for urethral reconstruction in rabbits. Flap angiogenesis is much higher than angiogenesis in simple wound closure. VEGF injection on postoperative day 3 seems to enhance angiogenesis in flaps. PMID- 22782325 TI - Treatment of plastic bronchitis using serial flexible bronchoscopy and aerosolized heparin therapy. PMID- 22782326 TI - Double purse string makes a nice umbilical ring: a novel technique for umbilicoplasty. PMID- 22782327 TI - In vivo assessment of bacteriotherapy on acetaminophen-induced uremic rats. AB - OBJECTIVES: Acetaminophen is a commonly used antipyretic agent which, at high doses, causes renal tubular damage and uremia. Bacteriotherapy affords a promising approach to mitigating uremic intoxication by ingestion of live microbes able to catabolize uremic solutes in the gut. The present study evaluates the nonpathogenic soil-borne urease-positive bacterium Sporosarcina pasteurii (Sp) as a potential urea-targeted component for such an "enteric dialysis" formulation. METHODS: Twenty-four albino male rats were randomly divided into 4 groups: The control group (group NC) received distilled water intraperitoneally for 7 days. The positive control group (group U) received 500 mg/kg acetaminophen intraperitoneally for 7 days. The tested group (group UP) was administered Sp at a dosage of 10(9) cells/day for 5 weeks, after receiving 500 mg/kg per day of acetaminophen intraperitoneally for 7 days. Vehicle control (group VC) received only Sp at a dosage of 10(9) cells/day for 5 weeks without acetaminophen treatment. Blood, kidney, liver and stool samples were collected after scarification, for biochemical (urea, creatinine, malondialdehyde, superoxide dismutase, catalase, glutamate oxaloacetate transaminase [GOT] and glutamate pyruvate transaminase [GPT] of blood, kidney and liver) tests. Limited fecal analysis was performed. RESULTS: Blood urea nitrogen (urea, creatinine) and toxicity indicators (GOT, GPT) were increased, and antioxidant enzymes were decreased in group U. Blood urea nitrogen and toxicity indicators were reduced, and antioxidant enzymes were increased significantly in the group UP (p<0.05) compared with group U. The number of Sp was increased in Sp-treated groups compared with groups NC and U. CONCLUSIONS: The study demonstrated that the bacteria tested reduced blood urea nitrogen levels significantly. PMID- 22782329 TI - Mycoplasma penetrans infection is a potential cause of immunoglobulin A nephropathy: a new animal model. AB - AIM: A new animal model of immunoglobulin A nephropathy (IgAN) was made by infecting mice with Mycoplasma penetrans (Mpe). To examine the pathogenesis of IgAN induced by Mpe infection, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and nuclear factor-kB (NF-kB) protein levels were compared among study groups. METHODS: To make an experimental IgAN animal model, mice were infected with Mpe, SP-4 medium or phosphate-buffered saline (PBS) via the urinary tract. To compare changes in the classical IgAN model, TNF-alpha and IL-6 RNA expression levels were measured using RT-PCR, and NF-kB protein was measured using EMSA. RESULTS: By producing a urinary tract infection with Mpe, we developed a new animal model of IgAN with a 100% success rate. There was no difference with the classical animal model. We also observed IgG deposition in 66.67% of the Mpe-infection group. Glomerular cell and mesangial matrix proliferation was greater in the Mpe-infection group than in the control groups (p<0.05). In the Mpe-infection and classical groups, TNF-alpha and IL-6 expression levels were much higher than in the control groups (p<0.01). NF-kB expression was much higher in the Mpe-infection group (p<0.05). CONCLUSIONS: We made a new IgAN animal model that will offer a new direction for IgAN research. The activation of inflammation factors was associated with the Mpe induction of IgAN. PMID- 22782328 TI - An update on calcium metabolism alterations and cardiovascular risk in patients with chronic kidney disease: questions, myths and facts. AB - In 2006, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines introduced, for the first time, the definition and diagnostic and therapeutic criteria for a systemic complication of the mineral metabolism dysfunction, such as vascular calcification, caused by chronic renal insufficiency. Abdominal x-ray and echocardiography rather than the more complex CT scan is suggested to make the diagnosis. This condition is associated with high cardiovascular risk and consequent poor prognosis. An alteration in total body calcium (Ca) content is one of the key factors in the cardiovascular complications observed in uremic subjects. In the general population, the addition of Ca to the diet has been to shown to improve bone mineral density (BMD) compared to controls, but it does not appear to reduce the risk of bone fractures. In patients with CKD, there are certainly some theoretical justifications for administering calcium salts: vitamin D deficiency, which reduces the intestinal absorption of Ca; hypocalcemia, which increases the risk of hyperparathyroidism; and hyperphosphatemia, which justifies the use of Ca-based P binders. There is already a large body of evidence pointing against the use of Ca-based binding agents, when there is a positive Ca balance because of the development of vascular calcification. PMID- 22782330 TI - The predictive role of p16 deletion, p53 deletion, and polysomy 9 and 17 in pancreatic ductal adenocarcinoma. AB - In this study, we investigated p53 and p16 deletions, and chromosome 9 and 17 amplifications in pancreatic ductal adenocarcinoma (PDAC), and further analyzed their associations with clinical characteristics and prognosis of PDAC. A total of 32 PDAC and 23 peritumoral tissues were collected. Molecular abnormalities of CEP9/p16 and CEP17/p53 were detected using Fluorescence in situ hybridization (FISH). Deletions of p16 and p53 were detected in 50 % and 65.7 % of PDAC, respectively. Polysomy 9 and 17 were identified in 75 % and 71.8 % of PDAC, respectively. No p16 and p53 deletion, polysomy 9 and 17 were identified in peritumoral tissues. We also observed significant correlations of p16 deletion, polysomy 9 and 17 with shorter survival of PDAC. P16 deletion, polysomy 9 and 17 are predictive markers for poor prognosis of PDAC patients, but p53 deletion is not associated with the clinical characteristics and prognosis of PDAC. PMID- 22782332 TI - Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up. AB - BACKGROUND: The purpose of this study was to report long-term results of rituximab induction monotherapy in patients with low-tumor-burden follicular lymphoma (LTBFL). PATIENTS AND METHODS: Of 49 first-line LTBFL patients who received weekly doses of rituximab (375 mg/m(2)), 46 have been followed with a long-term analysis of clinical and molecular responses. RESULTS: Best clinical response (at any staging within a year following treatment) was 80%, 24 (52%) patients had complete or unconfirmed complete response, 13 (28%) had partial response and 9 (20%) had stable or progressive disease. Of 31 patients having a positive bcl2-JH rearrangement, 15 (48%) became negative following treatment. After 83.9 months of follow-up (95% confidence interval 6.4-92.8 months), the median progression-free survival is 23.5 months and overall survival (OS) is 91.7%. Five patients died (one progression, one myelodysplasia, one diffuse large B-cell lymphoma and two solid tumors). Seven patients (15%) are progression-free including five who are bcl2 informative. No unexpected long-term adverse event has been observed. CONCLUSION: A significant proportion of patients remain progression-free 7 years after a single 4-dose rituximab treatment in first-line LTBFL. The 7-year overall survivalOS is very high in this selected population of patients. PMID- 22782331 TI - A randomized phase II study of irinotecan plus cisplatin versus irinotecan plus capecitabine with or without isosorbide-5-mononitrate in advanced non-small-cell lung cancer. AB - BACKGROUND: We investigated the efficacy of irinotecan/cisplatin (IP) versus irinotecan/capecitabine (IX) with or without isosorbide-5-mononitrate (ISMN) in chemo-naive advanced non-small-cell lung cancer. PATIENTS AND METHODS: Initially, 74 patients were randomly assigned to either IP or IX. Given the potential benefits of ISMN on chemotherapy, the protocol was amended during the study. Subsequently, 72 patients were randomly assigned to either IP + ISMN or IX + ISMN. Patients were treated with predefined second-line therapies (docetaxel/capecitabine for IP or IP + ISMN, docetaxel/cisplatin for IX or IX + ISMN) when disease progressed. RESULTS: A total of 146 received treatment. Response rate (RR), median progression-free survival (PFS) and overall survival (OS) were 49%, 5.5 months, 14.5 months in IP; 33%, 3.3 months, 13.0 months in IP + ISMN; 30%, 4.3 months, 16.1 months in IX; and 25%, 3.4 months, 13.6 months in IX + ISMN, respectively. While IP arm showed a trend toward higher RR and longer PFS than IX arm, IX arm showed a trend toward longer OS than IP arm. No significant differences were observed between IP + ISMN and IX + ISMN. CONCLUSION: IP showed better RR and PFS but no OS benefit when compared with IX. The addition of ISMN to IP or IX chemotherapy did not seem to improve the treatment outcome. PMID- 22782333 TI - Prophylactic cranial irradiation in small-cell lung cancer: findings from a North Central Cancer Treatment Group Pooled Analysis. AB - BACKGROUND: This pooled analysis evaluated the outcomes of prophylactic cranial irradiation (PCI) in 739 small-cell lung cancer (SCLC patients with stable disease (SD) or better following chemotherapy +/- thoracic radiation therapy (TRT) to examine the potential advantage of PCI in a wider spectrum of patients than generally participate in PCI trials. PATIENTS AND METHODS: Three hundred eighteen patients with extensive SCLC (ESCLC) and 421 patients with limited SCLC (LSCLC) participated in four phase II or III trials. Four hundred fifty-nine patients received PCI (30 Gy/15 or 25 Gy/10) and 280 did not. Survival and adverse events (AEs) were compared. RESULTS: PCI patients survived significantly longer than non-PCI patients {hazard ratio [HR] = 0.61 [95% confidence interval (CI): 0.52-0.72]; P < 0.0001}. The 1- and 3-year survival rates were 56% and 18% for PCI patients versus 32% and 5% for non-PCI patients. PCI was still significant after adjusting for age, performance status, gender, stage, complete response, and number of metastatic sites (HR = 0.82, P = 0.04). PCI patients had significantly more grade 3+ AEs (64%) compared with non-PCI patients (50%) (P = 0.0004). AEs associated with PCI included alopecia and lethargy. Dose fractionation could be compared only for LSCLC patients and 25 Gy/10 was associated with significantly better survival compared with 30 Gy/15 (HR = 0.67, P = 0.018). CONCLUSIONS: PCI was associated with a significant survival benefit for both ESCLC and LSCLC patients who had SD or a better response to chemotherapy +/- TRT. Dose fractionation appears important. PCI was associated with an increase in overall and specific grade 3+ AE rates. PMID- 22782334 TI - Acute gangrenous cholecystitis. PMID- 22782335 TI - The many faces of Hereditary Hemorrhagic Telangiectasia: median arcuate ligament syndrome, arteriovenous malformations, and cerebral aneurysms. PMID- 22782337 TI - Shedding light on unusual photophysical properties of bis-cyclometalated iridium(III) complexes containing 2,5-diaryl-1,3,4-oxadiazole-based and acetylacetonate ligands. AB - A DFT/TDDFT investigation was conducted on a series of cyclometalated iridium(iii) complexes with 2,5-diaryl-1,3,4-oxadiazole (oxd(n)) derivatives to shed light on the effects of the stereoisomeric and steric factors on the photophysical properties. On the basis of the results reported herein, we attempt to explain the experimental observations according to which complexes N,N-trans [Ir(oxd(0))(2)(acac)] (1a) and N,N-trans [Ir(oxd(1))(2)(acac)] (2a) [with oxd(0) = 2,5-diphenyl-1,3,4-oxadiazole, oxd(1) = 2,5-bis(4-fluorophenyl)-1,3,4 oxadiazole and acac = acetylacetonate] show high quantum phosphorescence efficiencies (Phi(PL)) of 35 and 44%, while an extremely low Phi(PL) (<1%) was observed for a number of oxd(n) based complexes including N,N-cis [Ir(oxd(3))(2)(acac)] (4b) [with oxd(3) = 2-(4-fluorophenyl)-5-(2,4,6 triisopropylphenyl)-1,3,4-oxadiazole]. While new insights were gained on structural and electronic properties, the unusual photophysical properties recently reported for 4b were found to be not inherent to spin-orbit coupling (SOC) effects, but determined by both the S(1)-T(1) splitting energy (DeltaE(S1 T1)) and the transition dipole moment (MU(S1)) upon the S(0)-> S(1) transition. Drastically large DeltaE(S1-T1) and small MU(S1) for 4b (0.70 eV and 0.23 D, respectively) comparative to those for 2a (0.38 eV and 2.76 D, respectively) and 1a (0.58 eV and 2.44 D, respectively) were found to be tightly linked to the twisting degree of the oxd(n) ligand and to the trans-cis structural isomerism. On the basis of these parameters, the unusual physical properties of 4b were interpreted with respect to 1a and 2a, and the higher Phi(PL) of 2a with respect to that for 1a was explained. PMID- 22782336 TI - Assessing pain in hospital in-patients: a cross-sectional study in Tuscany, Italy. AB - Guidelines Towards a Pain-Free Hospital, published in 2001 in Italy, determined an increasing spread of No-Pain Hospital Committees across the country and supported a more effective pain control in hospital. However, few hospitals adopted such protocols. To date, a thorough investigation on quality of pain management documentation is lacking. The present survey aimed to evaluate the quality of pain management documentation reported in medical and hospital discharge records. The study reviewed records of 2,459 patients discharged every Wednesday of November 2006 in 29 Tuscany hospitals. Among 2,459 patients, 51.5 % were males. Patients were aged between 0 and 90 years or above and were mostly (24.93 %) between 70 and 79 years; most of them (47.1 %) were hospitalized in Medicine ward. At hospital admission, less than half of examined records (40.3 %) reported pain-related items, and only 8.1 % reported how it was treated. During hospitalization, 39.6 % of the records reported the use of scales for measuring pain intensity and 49.7 % reported the pharmacological therapy. The present study highlights the lack of an exhaustive documentation of pain recording and management in the hospital setting. Therefore, healthcare providers should pay close attention to this relevant issue, and the quality of such documentation should be constantly monitored. PMID- 22782338 TI - Interpersonal relations between health care workers and young clients: barriers to accessing sexual and reproductive health care. AB - Interpersonal relations between health care providers and young clients have long being cited as an important element for improving client up take of services, satisfaction and overall health outcomes. In an era of HIV and AIDS this forms a critical determinant to young people accessing sexual and reproductive health care. This study explores to what extent interpersonal relations form a barrier to young peoples access to and satisfaction of health services. The study draws on data from 200 client exit interviews and four in-depth interviews conducted with university students and university health care staff in Kwazulu-Natal, South Africa. While young people are aware of the importance of utilising STI, HIV and family planning services they experienced barriers in their relationship with providers. This served as a deterrent to their use of the health facility. Adequate training in interpersonal relations for youth-friendly service provision is essential in helping overcome communication problems and enabling providers to interact with young clients at a more personal level. PMID- 22782339 TI - Lack of endothelial diaphragms in fenestrae and caveolae of mutant Plvap deficient mice. AB - Plasmalemmal vesicle-associated protein (PLVAP, PV-1) is specifically expressed in endothelial cells in which it localizes to diaphragms of fenestrae, caveolae, and transendothelial channels. To learn about its function, we generated mutant mice that lack PLVAP. In a C57BL/6N genetic background, homozygous Plvap deficient embryos die before birth and suffer from subcutaneous edema, hemorrhages, and defects in the vascular wall of subcutaneous capillaries. In addition, hearts of Plvap(-/-) embryos show ventricular septal defects and thinner ventricular walls. In wild-type embryos, PLVAP and caveolae with a stomatal diaphragm are present in endothelial cells of subcutaneous capillaries and endocardium, while a diaphragm is missing in caveolae of Plvap(-/-) littermates. Plvap(-/-) mice in a mixed C57BL/6N/FVB-N genetic background are born and survive at the most for 4 weeks. Capillaries of exocrine and endocrine pancreas and of kidney peritubular interstitium were investigated in more detail as examples of fenestrated capillaries. In these vascular beds, Plvap(-/-) mice show a complete absence of diaphragms in fenestrae, caveolae, and transendothelial channels, findings which are associated with a substantial decrease in the number of endothelial fenestrae. The changes in the capillary phenotype correlate with a considerable retardation of postnatal growth and anemia. Plvap(-/-) mice provide an animal model to clarify the specific functional role of endothelial fenestrae and their contribution to passage of water and solutes in different organs. PMID- 22782340 TI - Resistance to the mTOR-inhibitor RAD001 elevates integrin alpha2- and beta1 triggered motility, migration and invasion of prostate cancer cells. AB - BACKGROUND: Inhibitors of the mammalian target of rapamycin (mTOR) might become a novel tool to treat advanced prostate cancer. However, chronic drug exposure may trigger resistance, limiting the utility of mTOR inhibitors. METHODS: Metastatic potential of PC3 prostate cancer cells, susceptible (PC3(par)) or resistant (PC3(res)) to the mTOR-inhibitor RAD001 was investigated. Adhesion to vascular endothelium or immobilised collagen, fibronectin and laminin was quantified. Motility, migration and invasion were explored by modified Boyden chamber assay. Integrin alpha and beta subtypes were analysed by flow cytometry, western blotting and real-time PCR. Integrin-related signalling, EGFr, Akt, p70S6kinase and ERK1/2 activation were determined. RESULTS: Adhesion was reduced, whereas motility, migration and invasion were enhanced in PC3(res). The alpha2 and beta1 integrin subtypes were dramatically elevated, integrins alpha1 and alpha6 were lowered, whereas alpha5 was nearly lost in PC3(res). Activation of the Akt signalling pathway was strongly upregulated in these cells. Treating PC3(par) cells with RAD001 reduced motility, migration and invasion and deactivated Akt signalling. Blocking studies revealed that alpha2 and beta1 integrins significantly trigger the motile behaviour of the tumour cells. CONCLUSION: Chronic RAD001 treatment caused resistance development characterised by distinct modification of the integrin-expression profile, driving prostate cancer cells towards high motility. PMID- 22782342 TI - Serum markers lactate dehydrogenase and S100B predict independently disease outcome in melanoma patients with distant metastasis. AB - BACKGROUND: Established prognostic factors are of limited value to predict long term survival and benefit from metastasectomy in advanced melanoma. This study aimed to identify prognostic factors in patients with distant metastasis. METHODS: We analysed overall survival of 855 institutional melanoma patients with distant metastasis by bivariate Kaplan-Meier survival probabilities and multivariate Cox hazard regression analysis. RESULTS: Serum lactate dehydrogenases (LDH), S100B, the interval between initial diagnosis and occurrence of distant metastasis, the site of distant metastases, and the number of involved distant sites were significant independent prognostic factors in both bivariate and multivariate analyses. Visceral metastases other than lung (hazard ratio (HR) 1.8), elevated S100B (HR 1.7) and elevated LDH (HR 1.6) had the highest negative impact on survival. Complete metastasectomy was likewise an independent prognostic factor in multivariate analysis. This treatment was associated with favourable survival for patients with normal LDH and S100B values (5-year survival, 37.2%). CONCLUSION: The serum markers LDH and S100B were both found to be prognostic factors in melanoma patients with distant metastasis. Furthermore, complete metastasectomy had an independent favourable prognostic impact in particular for the patient subgroup with normal LDH and S100B values. PMID- 22782343 TI - Prospective randomised evaluation of traditional Chinese medicine combined with chemotherapy: a randomised phase II study of wild toad extract plus gemcitabine in patients with advanced pancreatic adenocarcinomas. AB - BACKGROUND: An intravenous formulated extract of the venom of the wild toad Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, huachansu, is currently used in China for the treatment of lung, liver, pancreatic, and colorectal cancers. We performed a randomised, single-blinded, phase II clinical study of huachansu plus gemcitabine versus placebo plus gemcitabine in patients with locally advanced and/or metastatic pancreatic adenocarcinomas. METHODS: Patients with tissue-proven locally advanced and/or metastatic pancreatic adenocarinoma were randomly assigned to receive either gemcitabine 1000 mg m(-2) on days 1, 8, and 15 with huachansu 20 ml m(-2) daily for 21 days (arm A) or placebo (arm B); treatment cycles were 28 days in length. Primary end point was 4-month progression-free overall survival (PFS); secondary end points were objective radiographical response rate (ORR), time to progression (TTP), and toxicity. RESULTS: A total of 80 subjects were enrolled; 76 patients were evaluable (received at least 1 week therapy). Median overall survival was 160 days for arm A and 156 days for arm B (P=0.339); ORR was 9 and 3% in arms A and B, respectively (P=0.332), median TTP was 98 and 115 days, respectively (P=0.825); the median 4-month PFS was 99 and 98 days, respectively (P=0.679). CONCLUSION: Huachansu when combined with gemcitabine did not improve the outcome of patients with locally advanced and/or metastatic pancreatic cancer. PMID- 22782341 TI - Secreted semaphorin 5A suppressed pancreatic tumour burden but increased metastasis and endothelial cell proliferation. AB - BACKGROUND: Our earlier reports demonstrated that membrane-bound semaphorin 5A (SEMA5A) is expressed in aggressive pancreatic cancer cells and tumours, and promotes tumour growth and metastasis. In this study, we examine whether (1) pancreatic cancer cells secrete SEMA5A and (2) that secreted SEMA5A modulates certain phenotypes associated with tumour progression, angiogenesis and metastasis through various other molecular factors and signalling proteins. METHODS AND RESULTS: In this study, we show that human pancreatic cancer cell lines secrete the extracellular domain (ECD) of SEMA5A (SEMA5A-ECD) and overexpression of mouse Sema5A-ECD in Panc1 cells (not expressing SEMA5A; Panc1 Sema5A-ECD; control cells - Panc1-control) significantly increases their invasion in vitro via enhanced ERK phosphorylation. Interestingly, orthotopic injection of Panc1-Sema5A-ECD cells into athymic nude mice results in a lower primary tumour burden, but enhances the micrometastases to the liver as compared with Panc1 control cells. Furthermore, there is a significant increase in proliferation of endothelial cells treated with conditioned media (CM) from Panc1-Sema5A-ECD cells and a significant increase in microvessel density in Panc1-Sema5A-ECD orthotopic tumours compared with those from Panc1-control cells, suggesting that the increase in liver micrometastases is probably due to increased tumour angiogenesis. In addition, our data demonstrate that this increase in endothelial cell proliferation by Sema5A-ECD is mediated through the angiogenic molecules - interleukin-8 and vascular endothelial growth factor. CONCLUSION: Taken together, these results suggest that a bioactive, secreted form of Sema5A-ECD has an intriguing and potentially important role in its ability to enhance pancreatic tumour invasiveness, angiogenesis and micrometastases. PMID- 22782344 TI - A short-term increase in cancer risk associated with daytime napping is likely to reflect pre-clinical disease: prospective cohort study. AB - BACKGROUND: Sleep disturbance, a correlate of which is daytime napping, has been hypothesised to be associated with risk of breast and other cancers. METHODS: We estimated relative risks (RR) of breast and other invasive cancers by the reported frequency of daytime napping in a large prospective cohort of middle aged women in the UK. RESULTS: During an average of 7.4 years of follow-up, 20 058 breast cancers and 31 856 other cancers were diagnosed. Over the first 4 years of follow-up, daytime napping (sometimes/usually vs rarely/never) was associated with slightly increased risks of breast cancer (RR=1.10, 95% CI 1.06 1.15) and of other cancers (RR=1.12, 1.08-1.15), but the RRs decreased significantly with increasing follow-up time (P=0.001 and P=0.01, respectively, for trend). Four or more years after baseline, there was no elevated risk of breast cancer (RR=1.00, 0.96-1.05), and only marginally greater risk of other cancers (RR=1.04, 1.01-1.07). CONCLUSION: The effect of pre-clinical disease is a likely explanation for the short-term increased risk of breast and other cancers associated with daytime napping. PMID- 22782345 TI - Accurate and rapid novel genetic diagnosis for detection of sentinel lymph node metastasis in breast cancer patients. AB - BACKGROUND: The transcription-reverse transcription concerted reaction (TRC) test is a novel molecular-based procedure, which can assess nodal metastasis accurately and quickly. We examined the usefulness of the TRC test with a double marker, cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) mRNA, to detect sentinel lymph nodes (SLN) metastasis in breast cancer patients. METHODS: A total of 264 SLNs from 131 breast cancer patients were assigned to a training set (109 SLNs from 50 patients) and validation set (155 SLNs from 81 patients). Cytokeratin 19 and CEA mRNA were detected by TRC tests, and the sensitivity and specificity of the SLN metastasis between the TRC and histology cohorts were compared. RESULTS: Mean copy numbers of CK19 and CEA by TRC tests were increased according to the metastatic size. In the training set, TRC test showed 100% sensitivity, specificity and concordance rates against the permanent histopathology test. In the validation set, sensitivity was 97.1%, specificity was 99.2% and the concordance rate was 99.4%. CONCLUSION: Our results showed that the detection of CK19 and CEA mRNA using the TRC test is, an accurate and rapid method for detection of SLN metastasis and can be applied as an intraoperative molecular diagnosis in breast cancer patients. PMID- 22782346 TI - EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer. AB - BACKGROUND: Proteolytic enzymes and their regulators have important biological roles in colorectal cancer by stimulating invasion and metastasis, which makes these factors attractive as potential prognostic biomarkers. METHODS: The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) was characterised using immunohistochemistry in primary tumours from a cohort of 277 prospectively recruited colorectal cancer patients, and associations with expression of S100A4, clinicopathological parameters and patient outcome were investigated. RESULTS: One hundred and ninety-eight samples (72%) displayed positive membrane staining of the tumour cells, whereas 10 cases (4%) were borderline positive. EMMPRIN expression was associated with shorter metastasis free, disease-specific and overall survival in both univariate and multivariate analyses. The prognostic impact was largely confined to TNM stage III, and EMMPRIN-negative stage III patients had an excellent prognosis. Furthermore, EMMPRIN was significantly associated with expression of S100A4, and the combined expression of these biomarkers conferred an even poorer prognosis. However, there was no evidence of direct regulation between the two proteins in the colorectal cancer cell lines HCT116 and SW620 in siRNA knockdown experiments. CONCLUSION: EMMPRIN is a promising prognostic biomarker in colorectal cancer, and our findings suggest that it could be used in the selection of stage III patients for adjuvant therapy. PMID- 22782347 TI - Comparison of screen-detected and interval colorectal cancers in the Bowel Cancer Screening Programme. AB - BACKGROUND: The NHS Bowel Cancer Screening Programme (BCSP) offers biennial faecal occult blood testing (FOBt) followed by colonoscopy after positive results. Colorectal cancers (CRCs) registered with the Northern Colorectal Cancer Audit Group database were cross-referenced with the BCSP database to analyse their screening history. METHODS: The CRCs in the screening population between April 2007 and March 2010 were identified and classified into four groups: control (diagnosed before first screening invite), screen-detected, interval (diagnosed between screening rounds after a negative FOBt), and non-uptake (declined screening). Patient demographics, tumour characteristics and survival were compared between groups. RESULTS: In all, 511 out of 1336 (38.2%) CRCs were controls; 825 (61.8%) were in individuals invited for screening of which 322 (39.0%) were screen detected, 311 (37.7%) were in the non-uptake group, and 192 (23.3%) were interval cancers. Compared with the control and interval cancer group, the screen-detected group had a higher proportion of men (P=0.002, P=0.003 respectively), left colon tumours (P=0.007, P=0.003), and superior survival (both P<0.001). There was no difference in demographics, tumour location/stage, or survival between control and interval groups. CONCLUSION: The FOBt is better at detecting cancers in the left colon and in men. The significant numbers of interval cancers weren't found to have an improved outcome compared with the non screened population. PMID- 22782348 TI - Site-specific CpG methylation in the CCAAT/enhancer binding protein delta (CEBPdelta) CpG island in breast cancer is associated with metastatic relapse. AB - BACKGROUND: The CCAAT/enhancer binding protein delta (CEBPdelta) is a member of a highly conserved family of basic region leucine zipper transcription factors. It has properties consistent with a tumour suppressor; however, other data suggest that CEBPdelta may be involved in the metastatic process. METHODS: We analysed the expression of CEBPdelta and the methylation status of the CpG island in human breast cancer cell lines, in 107 archival cases of primary breast cancer and in two series of metastatic breast cancers using qPCR and pyrosequencing. RESULTS: Expression of CEBPdelta is downregulated in primary breast cancer by site specific methylation in the CEBPdelta CpG island. Expression is also downregulated in 50% of cases during progression from primary carcinoma to metastatic lesions. The CEBPdelta CpG island is methylated in 81% metastatic breast cancer lesions, while methylation in the CEBPdelta CpG island in primary cancers is associated with increased risk of relapse and metastasis. CONCLUSION: CCAAT/enhancer binding protein delta CpG island methylation is associated with metastasis in breast cancer. Detection of methylated CEBPdelta genomic DNA may have utility as an epigenetic biomarker of primary breast carcinomas at increased risk of relapse and metastasis. PMID- 22782350 TI - Lipoprotein lipase is frequently overexpressed or translocated in cervical squamous cell carcinoma and promotes invasiveness through the non-catalytic C terminus. AB - BACKGROUND: We studied the biological significance of genes involved in a novel t(8;12)(p21.3;p13.31) reciprocal translocation identified in cervical squamous cell carcinoma (SCC) cells. METHODS: The rearranged genes were identified by breakpoint mapping, long-range PCR and sequencing. We investigated gene expression in vivo using reverse-transcription PCR and tissue microarrays, and studied the phenotypic consequences of forced gene overexpression. RESULTS: The rearrangement involved lipoprotein lipase (LPL) and peroxisome biogenesis factor 5 (PEX5). Whereas LPL-PEX5 was expressed at low levels and contained a premature stop codon, PEX5-LPL was highly expressed and encoded a full-length chimeric protein (including the majority of the LPL coding region). Consistent with these findings, PEX5 was constitutively expressed in normal cervical squamous cells, whereas LPL expression was negligible. The LPL gene was rearranged in 1 out of 151 cervical SCCs, whereas wild-type LPL overexpression was common, being detected in 10 out of 28 tissue samples and 4 out of 10 cell lines. Forced overexpression of wild-type LPL and PEX5-LPL fusion transcripts resulted in increased invasiveness in cervical SCC cells, attributable to the C-terminal non catalytic domain of LPL, which was retained in the fusion transcripts. CONCLUSION: This is the first demonstration of an expressed fusion gene in cervical SCC. Overexpressed wild-type or translocated LPL is a candidate for targeted therapy. PMID- 22782349 TI - Cervical human papillomavirus and HIV infection in women of child-bearing age in Abidjan, Cote d'Ivoire, 2010. AB - BACKGROUND: We sought to document the association of Human immunodeficiency Virus (HIV) infection and immunodeficiency with oncogenic Human Papillomavirus (HPV) infection in women with no cervical neoplastic lesions identified through a cervical cancer screening programme in Cote d'Ivoire. METHODS: A consecutive sample of women stratified on their HIV status and attending the national blood donor clinic or the closest HIV clinic was recruited during a cervical cancer screening programme based on the visual inspection. Diagnosis of HPV infection and genotype identification were based on the Linear Array; HPV test. RESULTS: A total of 445 (254 HIV-positive and 191 HIV-negative) women were included. The prevalence of oncogenic HPV infection was 53.9% (95% confidence interval (CI) 47.9-59.9) in HIV-positive women and 33.7% (95% CI 27.1-40.3) in HIV-negative women (odds ratio (OR)=2.3 (95% CI 1.5-3.3)). In multivariate analysis, HIV positive women with a CD4 count <200 cells mm(3) or between 200 and 499 cells mm(3) were more likely to harbour an oncogenic HPV compared with women with a CD4 count >=500 cells mm(3) with OR of 2.8 (95% CI 1.1-8.1) and 1.7 (95% CI 1.0-2.9), respectively. CONCLUSION: A high prevalence of oncogenic HPV was found in women with no cervical neoplastic lesions, especially in HIV-positive women. Despite antiretroviral use, immunodeficiency was a main determinant of the presence of oncogenic HPV. PMID- 22782351 TI - TIGAR induces p53-mediated cell-cycle arrest by regulation of RB-E2F1 complex. AB - BACKGROUND: p53 induces cell-cycle arrest and apoptosis in cancer cells and negatively regulates glycolysis via TIGAR. Glycolysis is crucial for cancer progression although TIGAR provides protection from reactive oxygen species and apoptosis. The relation between TIGAR-mediated inhibition of glycolysis and p53 tumour-suppressor activity is unknown. METHODS: RT-PCR, western blot, luciferase and chromatin immunoprecipitation assays were used to study TIGAR gene regulation. Co-IPP was used to determine the role of TIGAR protein in regulating the protein-protein interaction between retinoblastoma (RB) and E2F1. MCF-7 tumour xenografts were utilised to study the role of TIGAR in tumour regression. RESULTS: Our study shows that TIGAR promotes p21-independent, p53-mediated G1 phase arrest in cancer cells. p53 activates the TIGAR promoter only in cells exposed to repairable doses of stress. TIGAR regulates the expression of genes involved in cell-cycle progression; suppresses synthesis of CDK-2, CDK-4, CDK-6, Cyclin D, Cyclin E and promotes de-phosphorylation of RB protein. RB de phosphorylation stabilises the complex between RB and E2F1 thus inhibiting the entry of cell cycle from G1 phase to S phase. CONCLUSION: TIGAR mediates de phosphorylation of RB and stabilisation of RB-E2F1 complex thus delaying the entry of cells in S phase of the cell cycle. Thus, TIGAR inhibits proliferation of cancer cells and increases drug-mediated tumour regression by promoting p53 mediated cell-cycle arrest. PMID- 22782356 TI - Assessment of metal concentrations in muscles of the blue crab, Callinectes danae S., from the Santos Estuarine System. AB - This study determined the concentrations of eleven metals in the blue crab, Callinectes danae, from nine sites in the Santos Estuarine System of Sao Paulo State, Brazil. The results were compared to guidelines established in the United States, Europe and Brazil for the safety of human consumers. Muscles of blue crabs were removed by dissection and concentrations of Al, Cd, Co, Cr, Cu, Fe, Hg, Mn Ni, Pb and Zn were determined. In general, the concentrations of metals were low, and the crabs were regarded as safe for human consumption. Crabs from a single site (site 4) exceeded the guidelines established by the United States and Europe, but not Brazil, for Pb, with a mean tissue concentration of 1.725 MUg g( 1). With the exception of Al, Fe and Ni, significant differences were noted between sites in the concentrations of each metal in crab tissue. PMID- 22782352 TI - Effects of pioglitazone on platelet P2Y12-mediated signalling in clopidogrel treated patients with type 2 diabetes mellitus. AB - Patients with type 2 diabetes mellitus (T2DM) have impaired clopidogrel-induced antiplatelet effects, which may be in part attributed to their reduced sensitivity to insulin and consequently, results in upregulation of the P2Y12 signalling pathway. It has been hypothesised that insulin sensitising strategies may enhance clopidogrel-mediated P2Y12 inhibitory effects. The aim of this pilot pharmacodynamics (PD) study was to assess the impact of pioglitazone on clopidogrel-mediated P2Y12 inhibitory effects in patients with T2DM. This was a prospective, randomised, double-blind, placebo-controlled, cross-over PD study. Patients with T2DM and stable coronary artery disease on maintenance aspirin and clopidogrel were randomised to receive either pioglitazone 30 mg or matching placebo daily for 14 days. PD assessments were measured at baseline, 14 days after randomisation, at the end of the wash-out period, and 14 days after cross over. The primary endpoint measure was maximal platelet aggregation (MPA) to 20 MUM adenosine diphosphate (ADP) as assessed by light transmittance aggregometry (LTA). Flow cytometric analysis of vasodilator-stimulated phosphoprotein phosphorylation (VASP-PRI), and VerifyNow P2Y12 testing were also performed. A total of 15 randomised patients completed the study. MPA to 20 MUM ADP (primary endpoint) was not significantly different with pioglitazone compared with placebo (49.53 +/- 4.76 vs. 52.52 +/- 3.89%; p = 0.594). Similarly, other PD measures did not differ significantly between the groups. In conclusion, in patients with T2DM on maintenance aspirin and clopidogrel therapy, the adjunctive use of pioglitazone does not result in enhanced inhibition of platelet P2Y12 mediated signalling. PMID- 22782357 TI - Pesticide residue levels in green beans cultivated in Souss Masa valley (Morocco) after multiple applications of bifenthrin and lambda-cyhalothrin. AB - Dissipation of bifenthrin and lambda-cyhalothrin pyrethroid insecticides, under environmental conditions, was evaluated on green beans grown in experimental greenhouses (Souss Massa valley, Morocco). Pesticide residues were determined by gas chromatography with micro electron-capture detector (GC-MUECD) after dichloromethane extraction and cleanup on florisil phase cartridges. In the case of field experiments, a random block scheme was employed. Each block contained 25 plants in a single row and tests were carried out in triplicates applying pesticides at the recommended doses by the manufacturers. Fruit samples were periodically taken until the end of the preharvest interval (p.i.). The results obtained showed that the p.i of bifenthrin in green bean were 4 days in the winter and 3.5 days in the spring, whereas that for lambda-cyhalothrin 8 days was found in the winter and 7.5 days in the spring. Consequently, it is possible to consider the European Union maximum residue limit (EU MRL) values compatible with the proper agricultural practices used for growing green bean in the plastic greenhouse of Souss Massa valley in South Morocco. Bifenthrin had a degradation of first-order kinetics, whereas that of levels for lambda-cyhalothrin residue can not be interpreted by the use of a first order model. PMID- 22782358 TI - Removal of crude oil by microbial consortium isolated from oil-spilled area in the Korean Western coast. AB - The feasibility of using an indigenous microbial consortium for the removal of crude oil from an oil-spilled coastal area was explored with the ultimate aim of applying for bioremediation. Initially, we obtained the microbial consortium TK-2 that catalyzed the dispersion as well as the degradation of crude oil in supplemented sea water. GC and GC-MS were used to evaluate the removal patterns of crude oil during the incubation. The effective removal of crude oil by TK-2 occurred, and above 95% of all aliphatic and aromatic compounds detected in this work was removed within 30 days of incubation. Two predominant crude oil-grown isolates derived from TK-2 revealed gram-negative, rod-shaped cells. Both BIOLOG system and 16S rRNA sequencing were conducted to identify the strains, which were assigned to Arthrobacter sp. HK-2 and Pseudoalteromonas sp. HK-3, and registered in GenBank as [FJ477042] and [FJ477041]. PMID- 22782359 TI - Pesticide residues in tobacco leaves from the Kushtia district in Bangladesh. AB - In this study, tobacco leaf samples (n = 26) were collected from different areas in Kushtia to determine the presence of residues of cypermethrin, diazinon, heptachlor, methoxychlor dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethan (DDD) and dichlorodiphenyldichloroethylene (DDE). The analysis was conducted by a High Performance Liquid Chromatography (HPLC) system that was equipped with a photodiode array detector. Both cypermethrin and diazinon were detected in tobacco samples from six districts, namely, Mirzapur, Shahebnagar, Kodalipara, Pragpur, Farakpur and Taragunia. The highest concentration of cypermethrin was found in Kodalipara (2.00 ppm) while the highest concentration of diazinon was detected in a sample from Pragpur (0.15 ppm). The pesticide DDT was only detected in the sample from Pragpur at 4.00 ppm. This is the first study in Bangladesh that reports pesticide residue concentrations in tobacco leaf samples. PMID- 22782360 TI - Assessment of pollution in Ataturk Dam Lake (Adiyaman, Turkey) using several biochemical parameters in common carp, Cyprinus carpio L. AB - Ataturk Dam Lake, the largest impounded lake in Turkey, has been contaminated by domestic, industrial and agricultural effluents coming from Adiyaman city. In this study, we investigated the possible effects of pollutants on several biochemical parameters in the cyprinid fish, Cyprinus carpio, by comparing the parameters in fish collected from a polluted area (Sitilce) to a relatively clean area (Samsat) in August 2011. The activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase and levels of cortisol, glucose, and K increased while total protein, cholesterol, Ca, Na and Cl levels decreased in fish from the Sitilce site when compared to the Samsat site. The observed alterations in these biochemical parameters indicate that the Ataturk Dam Lake is affected by untreated wastewater discharges. PMID- 22782361 TI - Analysis of clinically relevant values of Ki-67 labeling index in Japanese breast cancer patients. AB - BACKGROUND: It has become important to standardize the methods of Ki-67 evaluation in breast cancer patients, especially those used in the interpretation and scoring of immunoreactivity. Therefore, in this study, we examined the Ki-67 immunoreactivity of breast cancer surgical specimens processed and stained in the same manner in one single Japanese institution by counting nuclear immunoreactivity in the same fashion. METHODS: We examined 408 Japanese breast cancers with invasive ductal carcinoma and studied the correlation between Ki-67 labeling index and ER/HER2 status and histological grade of breast cancer. We also analyzed overall survival (OS) and disease-free survival (DFS) of these patients according to individual Ki-67 labeling index. RESULTS: There were statistically significant differences of Ki-67 labeling index between ER positive/HER2 negative and ER positive/HER2 positive, ER negative/HER2 positive or ER negative/HER2 negative, and ER positive/HER2 positive and ER negative/HER2 negative groups (all P < 0.001). There were also statistically significant differences of Ki-67 labeling index among each histological grade (P < 0.001, respectively). As for multivariate analyses, Ki-67 labeling index was strongly associated with OS (HR 39.12, P = 0.031) and DFS (HR 10.85, P = 0.011) in ER positive and HER2 negative breast cancer patients. In addition, a statistically significant difference was noted between classical luminal A group and "20 % luminal A" in DFS (P = 0.039) but not between classical luminal A group and "25 % luminal A" (P = 0.105). CONCLUSIONS: A significant positive correlation was detected between Ki-67 labeling index and ER/HER2 status and histological grades of the cases examined in our study. The suggested optimal cutoff point of Ki-67 labeling index is between 20 and 25 % in ER positive and HER2 negative breast cancer patients. PMID- 22782362 TI - Same-sex sexual behaviors among male migrants in a context of male "marriage squeeze": results from an exploratory survey in urban Xi'an, China. AB - The male marriage squeeze in China may increase the prevalence of male same-sex sexual behaviors among unmarried male migrants who lack stable female sexual partners. The same-sex sexual behaviors among unmarried male migrants appear to be at high risk of transmission of human immunodeficiency virus (HIV) and sexually transmitted infections (STIs), mainly because of a lack of knowledge of these diseases. Using data from the "Survey on Reproductive Health and Family Life of Migrant Male Bachelors in Urban Areas" conducted in Xi'an City, Shaanxi Province, in December 2009 and January 2010, this study compares same-sex sexual behaviors of unmarried with that of married male migrants (including married but separated men who are migrating without their spouse or partner and cohabitating men who are migrating with their spouse or partner). It is reported that the prevalence of same-sex sexual behaviors among unmarried males reaches 11%, more than twice the 5.1% reported by married but separated men and thrice the 3.8% reported by cohabitating men. It also appears that the same-sex sexual behaviors is significantly associated with men's attitudes toward same-sex sexual behaviors (odds ratio = 1.59, p < .001), toward life-long bachelorhood (odds ratio = 1.35, p < .01), and with marital status (odds ratio = 0.37, p < .01). The frequency of condom use appears to be higher among unmarried men than among men who are married, whether or not they migrated with their wives, and is significantly associated with scores on knowledge about HIV/AIDS (estimated coefficient = .12, p < .001) and STIs (estimated coefficient = .22, p < .01). It is also associated with the likelihood of same-sex sexual behaviors (estimated coefficients = .83, p < .01) and marital status (estimated coefficients for married but separated = .50, p < .05; estimated coefficients for cohabitating = -.77, p < .001). PMID- 22782363 TI - Does nerve identification during open inguinal herniorrhaphy reduce the risk of nerve damage and persistent pain? AB - PURPOSE: Nerve identification during open inguinal hernia herniorrhaphy has been suggested as one of the factors that may reduce the risk of development of persistent postherniorrhaphy pain. In this prospective study, we evaluated whether intraoperative inguinal nerve identification influenced the risk of development of persistent postherniorrhaphy pain, sensory dysfunction in the groin and functional ability score after open hernia repair. METHODS: A total of 244 men with a primary inguinal hernia underwent open Lichtenstein repair in a high-volume hernia surgery centre, where information on inguinal nerve identification was registered during operation. Before the operation and 6 months postoperatively, functional pain-related impairment was assessed with Activities Assessment Scale and pain intensity scores with Numeric Rating Scale (NRS 0-10). Quantitative sensory testing in the groin was performed before operation and 6 months postoperatively, in order to investigate intraoperative inguinal nerve damage. RESULTS: The intraoperative nerve identification rates for the iliohypogastric, ilioinguinal and genitofemoral nerves were 94.7, 97.5 and 21.3 %, respectively. Thirty-nine patients (16.0 %) had substantial pain-related functional impairment at 6 months follow-up. There was no difference in risk of development of substantial pain-related functional impairment in patients with identification compared with non-identification of the iliohypogastric nerve (P = 1.0), the ilioinguinal nerve (P = 0.59), the genitofemoral nerve (P = 0.40) or all nerves (P = 0.52). There were no differences in regard to sensory loss in the groin area or in regard to improvement in functional outcome following surgery, between patients with and without nerve identification. CONCLUSIONS: Although intraoperative inguinal nerve identification should be aimed at, other factors may contribute to the risk of nerve damage and persistent pain after open groin hernia repair. PMID- 22782364 TI - Prevention of parastomal hernia by intraperitoneal onlay mesh reinforcement at the time of stoma formation. AB - PURPOSE: Parastomal hernia (PSH) is a very frequent complication after creation of a permanent colostomy. The aim of this study is to assess the safety and prophylactic effect of intraperitoneal onlay mesh (IPOM) reinforcement of the abdominal wall at the time of primary stoma formation to prevent PSH occurrence. MATERIALS AND METHODS: This multicentre prospective study concerned 20 patients operated for low rectal carcinoma between 2008 and 2010. Those patients had an elective and potentially curative abdominoperineal excision associated with IPOM reinforcement of the abdominal wall with a round composite mesh centred on the stoma site and covering the lateralised colon. There were 8 men and 12 women with a median age of 69 years (range: 44-88) and a body mass index of 27 (range: 21 35). The major outcomes analysed in the study were operative time, complications related to mesh and PSH occurrence. Patients were evaluated 1 month after surgery and then every 6 months with physical examination and computed tomography scan (CT-scan). For PSH, we used the classification of Moreno-Matias. RESULTS: Surgery was performed by laparoscopy in 17 patients and by laparotomy in 3; 12 had an extraperitoneal colostomy, and 8 had a transperitoneal colostomy. The median size of the mesh was 15 cm (range: 12-15). The median operative time was 225 min (range: 175-300), and specific time for mesh placement was 15 min (range: 12-30). One month after surgery, one patient presented with a mild stoma stenosis that was treated successfully by dilatation. With a median follow-up of 24 months (range: 6-42), no other complication potentially related to the use of the mesh was recorded and no mesh had to be removed. On clinical examination, one patient (1/20 = 5 %) had a stoma bulge that appeared a few months after surgery, but was not associated with symptoms. CT-scan evaluation confirmed that all the patients with a normal clinical examination had no PSH and revealed that the patient with the stoma bulge had a stoma loop hernia (type 1a hernia). This patient was followed up for 36 months, no clinical or radiological aggravation of the stoma loop hernia was observed, and he remained totally asymptomatic. CONCLUSIONS: With 95 % of excellent results, IPOM reinforcement at the time of end colostomy formation in selected patients is a very promising procedure. A drawback of this technique is the possibility of developing a stoma loop hernia due to sliding of the exiting colon between the covering mesh and the abdominal wall. However, this risk is low, and no adverse clinical consequence for the patient was noted in our series. PMID- 22782365 TI - The effect of a chitosan coating on the adhesive potential and tensile strength of polypropylene meshes. AB - PURPOSE: The polypropylene mesh used for the repair of abdominal wall hernia can cause intraabdominal adhesions. In this study, the effect of chitosan coating of the polypropylene meshes on the adhesion and tensile strength of the meshes was investigated. METHOD: After coating polypropylene meshes with 2 % chitosan, 5 * 3 cm patches were prepared. Under general anesthesia, sterile laparotomy was performed in 96 Wistar albino female rats that were equally allocated to 6 groups. In the first group, only laparotomy was performed. In the second group, chitosan was applied to the peritoneal cavity, and the laparotomy was closed. In the third group, polypropylene (prolene) patches were used to close the abdomen; in the fourth group, polypropylene polyglecaprone 25 (ultrapro) mesh patches were used to close the abdomen. In the fifth and sixth groups, chitosan-coated versions of the meshes used in the third and fourth groups, respectively, were applied. All skin incisions were closed in all groups. On the 7th and 21st days, eight randomly selected rats from each group were killed. The abdomen was opened, and the adhesions were evaluated using the diamond score. The tensile strength of the meshes was measured by an Instron 4301 device. The histopathological evaluation of the inflammatory response was performed according to the Ehrlich and Hunt classification. RESULTS: The adhesion score was comparable among mesh groups but higher when mesh groups were compared with the control and chitosan groups (p<0.001). The tensile strength of meshes did not differ among mesh groups. Histopathologically, meshes with or without chitosan were similar in terms of inflammatory findings. CONCLUSIONS: The chitosan coating did not affect the adhesion potential, the tensile strength, or the inflammatory response of the polypropylene meshes. PMID- 22782366 TI - Three-year results of randomised clinical trial comparing lightweight mesh with heavyweight mesh for inguinal hernioplasty. AB - PURPOSE: The aim of the present randomised study was to find out whether usage of lightweight mesh in inguinal hernia repair, compared with heavyweight mesh, results in decreased incidence of chronic groin pain and foreign body feeling, as well as to evaluate the risk factors for chronic pain development and hernia recurrences. METHODS: The patients were randomised into the heavyweight mesh (HW) group and lightweight mesh (LW) group. A tension-free mesh repair using the Lichtenstein technique was performed on all patients. Pain scores during different activities were measured on visual analogue scale. All patients underwent a clinical examination for any evidence of hernia recurrence. RESULTS: Of the patients, 17.2 % in the HW group and 29.3 % in the LW group reported that they experienced pain at 3-year follow-up (P = 0.1323). Pain was most often reported during physical activity. The median VAS score of all studied activities was 30.5 in the HW group and 30.0 in the LW group. There were more patients in the HW group than in the LW group who stated that they could feel the mesh in the groin (27.6 vs. 20.7 %, P = 0.3967). Among all patients, 42.9 % who had severe pain preoperatively also reported pain during different activities and 19.6 % of the patients who did not have severe pain preoperatively reported pain during different activities (P = 0.0481). At 3-year follow-up, there was 1 hernia recurrence in the HW group and 1 hernia recurrence in the LW group. CONCLUSIONS: Our study shows that compared with HW mesh, LW mesh has no advantage in reducing chronic groin pain and foreign body feeling at the operation site after inguinal hernioplasty at 3-year follow-up. Severe preoperative pain was correlated with the development of chronic pain. There was no difference between the two study groups in the recurrence rates. PMID- 22782367 TI - Use of a prosthetic mesh to prevent parastomal hernia during laparoscopic abdominoperineal resection: a randomized controlled trial. AB - PURPOSE: Prevention of parastomal hernia represents an important aim when a permanent stoma is necessary. The objective of this work is to assess whether implantation of a prophylactic prosthetic mesh during laparoscopic abdominoperineal resection contributed to reduce the incidence of parastomal hernia. METHODS: Rectal cancer patients undergoing elective laparoscopic abdominoperineal resection with permanent colostomy were randomized to placement of a large-pore lightweight mesh in the intraperitoneal/onlay position by the laparoscopic approach (study group) or to the control group (no mesh). Parastomal hernia was defined radiologically by a CT scan performed after 12 months of surgery. The usefulness of subcutaneous fat thickness measured by CT to discriminate patients at risk of parastomal hernia was assessed by ROC curve analysis. RESULTS: Thirty-six patients were randomized, 19 to the mesh group and 17 to the control group. Parastomal hernia was detected in 50 % of patients in the mesh group and in 93.8 % of patients in the control group (P = 0.008). The AUC for thickness of the subcutaneous abdominal was 0.819 (P = 0.004) and the optimal threshold 23 mm. Subcutaneous fat thickness >=23 mm was a significant predictor of parastomal hernia (odds ratio 15.7, P = 0.010), whereas insertion of a mesh was a protective factor (odds ratio 0.06, P = 0.031). CONCLUSIONS: Use of prophylactic large-pore lightweight mesh in the intraperitoneal/onlay position by a purely laparoscopic approach reduced the incidence of parastomal hernia formation. Subcutaneous fat thickness >=23 mm measured by CT was an independent predictor of parastomal hernia. PMID- 22782368 TI - Long-term follow-up after incisional hernia repair: are there only benefits for symptomatic patients? AB - INTRODUCTION: Incisional hernias are among the most frequent complications in visceral surgery and are currently considered to be an indication for surgery in all cases, regardless of the patient's symptoms. However, it still remains unclear to what extent surgery actually results in improvement according to objective (e.g., less pain or dysesthesia) or subjective criteria (e.g., less discomfort or better cosmetic result). The purpose of this prospective study was to identify patients who derive objective and subjective benefit from surgical repair. MATERIALS AND METHODS: This prospective study included patients who underwent open incisional hernia repair with mesh implantation from December 2006 to April 2009. Data were collected before and 18 months after surgery. Pain intensity was rated on the numerical analog scale (NAS) pre- and postoperatively. Patients were divided into oligosymptomatic (NAS 0-3) and symptomatic (NAS 4-10) groups based on their preoperative pain level, and the postoperative outcome of the two groups was compared by standardized questionnaire. RESULTS: Ninety patients were prospectively enrolled, 45 (50 %) of each gender. Prior to surgery, 43 patients (47.8 %) were oligosymptomatic, and 47 (52.2 %) reported clinically relevant pain. Eighteen months after surgery, 7.5 % of the oligosymptomatic patients complained of clinically relevant pain; its rate remained unchanged. The symptomatic group showed a significant reduction in clinically relevant pain from 100 % to 14.0 %, (p < 0.001). The percentage of patients with clinically relevant dysesthesia was 12.5 % in the oligosymptomatic and 20.9 % in the symptomatic group 18 months postoperatively. The overall recurrence rate was 13.3 % after 18 months without difference in both groups. A reduction in discomfort in the surgical area was reported by 77.5 % of the oligosymptomatic and 79.1 % of the symptomatic patients. CONCLUSIONS: Symptomatic patients definitely profit from surgical repair in the long-term course. However, the notable postoperative rate of clinically relevant pain and dysesthesia in oligosymptomatic patients and their high recurrence rate cast doubt on whether they really benefit from surgical repair. The remarkable degree of subjective satisfaction in oligosymptomatic patients should not be underestimated. PMID- 22782369 TI - Comparison of vitrification and slow cooling for umbilical tissues. AB - The tissue cryopreservation maintains the cellular metabolism in a quiescence state and makes the conservation possible for an indefinite period of time. The choice of an appropriate cryopreservation protocol is essential for maintenance of cryopreserved tissue banks. This study evaluated 10 samples of umbilical cord, from which small fragments of tissue (Wharton's jelly and cord lining membrane) were subjected to two protocols of cryopreservation: slow cooling and vitrification. The samples were frozen for a period of time ranging from 5 to 78 days. The efficiency of cryopreservation was evaluated by testing cell viability, histological analysis, cell culture, cytogenetic analysis and comparison with the results of the fresh samples. The results showed that the slow cooling protocol was more efficient than the vitrification for cryopreservation of umbilical cord tissue, because it has caused fewer changes in the structure of tissue (edema and degeneration of the epithelium) and, despite the significant decrease cell viability compared to fresh samples, the ability of cell proliferation in vitro was preserved in most samples. In conclusion, this study showed that it is possible to cryopreserve small fragments of tissue from the umbilical cord and, to obtain viable cells capable of proliferation in vitro after thawing, contributing to the creation of a frozen tissue bank. PMID- 22782370 TI - Correcting the effects of -20 degrees C storage and aliquot size on erythrocyte fatty acid content in the Women's Health Initiative. AB - Red blood cell (RBC) fatty acid (FA) patterns have been shown to predict risk for cardiovascular and other chronic diseases. As part of a project analyzing RBC samples from the Women's Health Initiative Memory Study (WHIMS) we observed implausibly low levels of highly unsaturated fatty acids (HUFA) suggestive of degradation. This was hypothesized to be due to short term storage (<1 month) at 20 degrees C during sample aliquoting. The purpose of this study was to measure the extent of degradation that occurs under these conditions, and then to use regression calibration equations with multiple imputations to correct the biases. Samples from the Women's Health Initiative that had always been stored at -80 degrees C were obtained and subjected to similar conditions as the WHIMS samples. General linear mixed models were used to develop bias-corrected calibration equations for each fatty acid. Sample degradation occurred at -20 degrees C with the average HUFA loss of 3.5 to 5.9 % per week depending on aliquot size (250 and 80 uL, respectively). Using the ratio of HUFA to saturated fatty acids (HUFA/SAT) as a marker of degradation, this bias-correction method raised the HUFA/SAT from 0.70 to 0.81, which was similar to that (0.78) seen in another large study with optimal processing. In summary, RBC samples should always be stored at -80 degrees C. The FA compositions of the degraded RBC samples from WHIMS were rehabilitated by application of regression calibration equations and multiple imputations, and these imputed datasets should be used in all future WHIMS studies. PMID- 22782371 TI - trans-10,cis-12 conjugated linoleic acid enhances endurance capacity by increasing fatty acid oxidation and reducing glycogen utilization in mice. AB - The supplementation of conjugated linoleic acid (CLA) has been shown to improve endurance by enhancing fat oxidation during exercise in rodents and humans. This study was designed to investigate the isomer-specific effects of CLA on endurance capacity and energy metabolism in mice during exercise. Male 129Sv/J mice were divided into three dietary groups and fed treatment diet for 6 weeks; control, 0.5 % cis-9,trans-11 (c9,t11) CLA, or 0.5 % trans-10,cis-12 (t10,c12) CLA. Dietary t10,c12 CLA induced a significant increase in maximum running time and distance until exhaustion with a dramatic reduction of total adipose depots compared to a control group, but there were no significant changes in endurance with the c9,t11 CLA treatment. Serum triacylglycerol and non-esterified fatty acid concentrations were significantly lower in the t10,c12 fed mice after exercise compared to control and the c9,t11 CLA fed-animals. Glycogen contents in livers of the t10,c12 fed-mice were higher than those in control mice, concomitant with reduction of serum L-lactate level. There were no differences in non-exercise physical activity among all treatment groups. In addition, the mRNA expression levels of carnitine palmitoyl transferase 1beta, uncoupling protein 2 and peroxisome proliferator-activated receptor delta (PPARdelta) in skeletal muscle during exercise were significantly up-regulated by the t10,c12 CLA but not the c9,t11 CLA. These results suggest that the t10,c12 CLA is responsible for improving endurance exercise capacity by promoting fat oxidation with a reduction of the consumption of stored liver glycogen, potentially mediated via PPARdelta dependent mechanisms. PMID- 22782372 TI - Nanomaterials in complex biological systems: insights from Raman spectroscopy. AB - The interaction of nanomaterials with biomolecules, cells, and organisms plays an important role in cell biology, toxicology, and nanotechnology. Spontaneous Raman scattering can be used to probe biomolecules, cells, whole animals, and nanomaterials alike, opening interesting avenues to study the interaction of nanoparticles with complex biological systems. In this review we discuss work in biomedical Raman spectroscopy that has either been concerned directly with nanostructures and biosystems, or that indicates important directions for successful future studies on processes associated with nano-bio-interactions. PMID- 22782373 TI - Role of the mechanical axis of lower limb and body weight in the horizontal tear and root ligament tear of the posterior horn of the medial meniscus. AB - PURPOSE: To compare and analyse the relationship between horizontal tear and root ligament tear of the posterior horn of the medial meniscus (PHMM) and the degree of varus in the axis of lower limb and body weight. METHODS: One hundred and nineteen patients underwent surgical treatment as they were diagnosed with medial meniscus tear in our hospital from May 2006 to December 2009. Of these, 19 cases (group 1), underwent partial meniscectomy as they were confirmed to solely have horizontal tear of the PHMM on arthroscopic examination and 27 cases (group 2), underwent subtotal meniscectomy as they were confirmed to solely have root ligament tear of the PHMM on arthroscopic examination, were chosen for retrospective study. Standing radiographs were taken of every case prior to arthroscopic surgery to measure varus angle. Also, we checked body mass index (BMI) of two groups. The difference of varus angle and BMI between two groups were statistically verified using the Levene's test, paired t-test. RESULTS: Group 1 showed mean value of varus angle of 2.30 +/- 0.54, and BMI of 25.32 +/- 3.23. Group 2 showed mean value of varus angle of 5.64 +/- 0.54, and BMI of 25.67 +/- 3.12. The degree of varus of group 2 was statistically significantly higher than group 1 (p = 0.002). Comparison between the BMI of two groups showed no statistical significance (p = 0.053). CONCLUSION: Through a comparative study of sole horizontal tear and root ligament tear of the PHMM, the authors have found that sole root ligament tear of the PHMM is more relative to the genu varum than sole horizontal tear of the PHMM. However, body weight was statistically irrelevant to the incidence of the two lesions. PMID- 22782374 TI - Z-shortening of healed, elongated Achilles tendon rupture. AB - PURPOSE: A rupture of the Achilles tendon may heal in continuity, resulting in a lengthened Achilles tendon. The elongated structure must be shortened to restore effective push off. We report the results of a longitudinal study using Z shortening of ruptured Achilles tendons that healed in continuity but were elongated. METHODS: Nine patients underwent surgery for elongation of a healed Achilles tendon rupture. All participants were prospectively followed up for two to five years, and final review was performed at 32 +/- 14 months from operation. Clinical and functional assessment (anthropometric measurements, isometric strength, postoperative total rupture score) was performed. RESULTS: All patients were able to walk on tiptoes, and no patient used a heel lift or walked with a visible limp. No patient developed clinically evident deep-vein thrombosis or sustained a rerupture. Two patients were managed conservatively following a superficial surgical wound infection. At final review, maximum calf circumference remained significantly decreased in the operated leg. The operated limb was significantly weaker than the nonoperated one. CONCLUSIONS: Managing a healed Achilles tendon rupture using Z-shortening is safe and effective, providing good recovery and early weight bearing and active ankle mobilisation. Such patients should be warned that they are at risk for postoperative complications and that their ankle-plantar flexion strength is likely to be permanently reduced. PMID- 22782376 TI - Resistant plantar fasciopathy: shock wave versus endoscopic plantar fascial release. AB - PURPOSE: To compare the results of Extracorporeal shock wave (ESWT) with a modified endoscopic plantar fasciotomy technique for the treatment of recalcitrant heel pain. METHOD: Sixty-five patients suffering from chronic heel pain that failed to respond to standard nonoperative methods were randomized to undergo either high-energy extracorporeal shock wave therapy (group 1), or modified endoscopic plantar fasciotomy (group 2). The primary outcome measure was the reduction of pain in the two groups from base line to month three post intervention at the first few steps in the morning. In addition, patients' functions were assessed using American Orthopedic Foot and Ankle-Hindfoot Scale (AOFAS) at week three, month three, and month 12 post-intervention, and finally, Roles and Maudsley scores were assessed. The primary analysis was intention-to treat and involved all patients who were randomly assigned. RESULTS: Both groups achieved improvement from the base line at 3 weeks, 3 months and 12 months post intervention. The success rate (Roles and Maudsley score excellent and good) in the ESWT group at month 12 was 70.6 %, while in the fasciotomy group, the success rate was 77.4 % (p = 0.19). CONCLUSION: In patients who had experienced failure of conventional treatment of plantar fasciopathy, both endoscopic plantar fasciotomy and shock wave therapy can be potentially helpful lines of management. PMID- 22782377 TI - Reply to comments on: Assessment of inter- and intra-observer reliability in the determination of radiographic version and inclination of the cup in metal-on metal hip resurfacing. PMID- 22782378 TI - An international survey on anterior cruciate ligament reconstruction practices. AB - PURPOSE: Bone-patellar-tendon-bone (BPTB) autografting fixed with metal interference screws (IS) is the gold standard for anterior cruciate ligament (ACL) reconstruction. Advances in surgical technology provide a wide choice of grafts, fixation devices and surgical approaches. METHODS: Two-hundred and sixty one orthopedic surgeons of ten subspecialties from 57 countries were surveyed on their choice of graft and fixation device, the number of reconstructed bundles, and arthroscopic portal. Their preferences were analyzed according to country of origin, field of expertise and seniority, and compared to current publications. RESULTS: Hamstring autografting was the most popular choice (63 %), then BPTB (26 %) and allograft (11 %). The anteromedial portal was preferred over the traditional transtibial portal (68 % versus 31 %). Two-thirds reported routinely performing a single-bundle graft reconstruction, compared to one-third who used the double-bundle technique. The Endo-button was the most common graft fixation method (40 %), followed by the bioabsorbable IS (34 %), metallic IS (12 %), rigidfix (10 %) and others (4 %). The preferences of hamstring tendon grafting and the anteromedial portal are not supported in the literature. Responses from North American and European surgeons were different from all the others. CONCLUSIONS: Surgeon preferences in ACL reconstruction differ considerably worldwide. Common practice is not always supported by evidence-based publications. PMID- 22782379 TI - Investigation of diachronic dietary patterns on the islands of Ibiza and Formentera, Spain: evidence from sulfur stable isotope ratio analysis. AB - We present sulfur isotope ratio measurements of bone collagen from animals (n = 75) and humans (n = 120) from five sites dating to four chronological periods (Chalcolithic, Punic, Late Antiquity-Early Byzantine, and Islamic) from the Balearic Islands of Ibiza and Formentera, Spain. This study is a follow up to previously published delta(13)C and delta(15)N values by [Fuller et al.: Am J Phys Anthropol 143 (2010) 512-522] and focuses on using delta(34)S values to better understand the dietary patterns of these populations through time and to possibly identify immigrants to these islands. The range of delta(34)S values (10.5-17.80/00) observed for the animals was relatively broad, which suggests that a significant sea spray effect has added marine sulfates to the soils of Formentera and Ibiza. The mean delta(34)S values of the different human populations were found to be: Chalcolithic (16.5 +/- 1.40/00), Punic rural (13.6 +/- 1.70/00), Punic urban (12.9 +/- 1.80/00), Late Antiquity-Early Byzantine (12.3 +/- 2.10/00), and Islamic (9.1 +/- 2.70/00). These human delta(34)S results are similar to the animal data, a finding that supports the notion that there was little marine protein consumption by these societies and that the diet was mainly based on terrestrial resources. During the Punic and Late Antiquity-Early Byzantine periods the delta(34)S values were used to identify individuals in the population who likely were not born or raised on the islands. In addition, 18 of the 20 individuals analyzed from the Islamic period have delta(34)S values that indicate that they were immigrants to Ibiza who died before acquiring the new local sulfur isotopic signature. PMID- 22782380 TI - Alpha-methylacyl-coenzyme A racemase expression in neuroendocrine neoplasms of the stomach. AB - The enzyme alpha-methylacyl-coenzyme A racemase plays an important role in the beta-oxidation of branched-chain fatty acid and its derivatives. It has been used to detect prostatic adenocarcinoma and high-grade intraepithelial neoplasia, and recently also as a marker for other neoplasms, including those of the genitourinary system, breast, upper and lower gastrointestinal tract and their precursor lesions. We assessed expression of alpha-methylacyl-coenzyme A racemase by immunohistochemistry in neuroendocrine tumours of the stomach to determine differences in the incidence and pattern of expression among different types of gastric neuroendocrine tumours. While none of the grade 1 neuroendocrine tumours were immunoreactive, 67 % of grade 2 neuroendocrine tumours and 90 % of neuroendocrine carcinomas were positive for alpha-methylacyl-coenzyme A racemase. Furthermore, an adenocarcinoma component was found in 72.5 % (37 of 51) of neuroendocrine carcinomas, whereas none of the grade 1 and 2 neuroendocrine tumours contained an adenocarcinoma component. In 83 % of neuroendocrine carcinomas, the adenocarcinoma component was positive for alpha-methylacyl coenzyme A racemase, and both adenocarcinoma and neuroendocrine carcinoma components stained positively in 78 % of these cases. Our results indicate that alpha-methylacyl-coenzyme A racemase is a useful marker for distinguishing between grade 1 (negative) and grade 2 neuroendocrine tumours, and neuroendocrine carcinoma of the stomach (frequently positive). Different patterns of alpha methylacyl-coenzyme A racemase expression between gastric neuroendocrine tumours and neuroendocrine carcinoma suggest that these might develop via different tumourigenic pathways. PMID- 22782382 TI - A description of large-scale metabolomics studies: increasing value by combining metabolomics with genome-wide SNP genotyping and transcriptional profiling. AB - The metabolome, defined as the reflection of metabolic dynamics derived from parameters measured primarily in easily accessible body fluids such as serum, plasma, and urine, can be considered as the omics data pool that is closest to the phenotype because it integrates genetic influences as well as nongenetic factors. Metabolic traits can be related to genetic polymorphisms in genome-wide association studies, enabling the identification of underlying genetic factors, as well as to specific phenotypes, resulting in the identification of metabolome signatures primarily caused by nongenetic factors. Similarly, correlation of metabolome data with transcriptional or/and proteome profiles of blood cells also produces valuable data, by revealing associations between metabolic changes and mRNA and protein levels. In the last years, the progress in correlating genetic variation and metabolome profiles was most impressive. This review will therefore try to summarize the most important of these studies and give an outlook on future developments. PMID- 22782381 TI - Chondroclasts are mature osteoclasts which are capable of cartilage matrix resorption. AB - Multinucleated cells termed chondroclasts have been observed on the deep surface of resorbed hyaline cartilage but the relationship of these cells to macrophages and osteoclasts and their role in rheumatoid arthritis (RA) and other arthritic conditions is uncertain. Multinucleated cells in RA and other arthritic conditions showing evidence of cartilage resorption were characterised immunohistochemically for expression of macrophage/osteoclast markers. Mature human osteoclasts formed from circulating monocytes and tissue macrophages were cultured for up to 4 days on slices of human cartilage and glycosaminoglycan (GAG) release was measured. Multinucleated cells resorbing unmineralised cartilage were seen in osteoarthritis, RA, septic arthritis, avascular necrosis and in four cases of giant cell tumour of bone that had extended through the subchondral bone plate. Chondroclasts expressed an osteoclast-like phenotype (TRAP+, cathepsin K+, MMP9+, CD14-, HLA-DR-, CD45+, CD51+ and CD68+). Both macrophages and osteoclasts cultured on cartilage released GAG. These findings indicate that chondroclasts have an osteoclast-like phenotype and that mature human osteoclasts are capable of cartilage matrix resorption. Resorption of unmineralised subchondral cartilage by chondroclasts and macrophages can be a feature of joint destruction in inflammatory and non-inflammatory arthropathies as well as inflammatory and neoplastic subchondral bone lesions. PMID- 22782383 TI - Glucocorticoid receptor activation following elevated oocyte cortisol content is associated with zygote activation, early embryo cell division, and IGF system gene responses in rainbow trout. AB - Increased in ovo cortisol content of rainbow trout oocytes from ~3.5 to ~5.0 ng.oocyte(-1) before fertilization enhances the growth of embryos and juveniles and changes the long-term expression pattern of IGF-related genes. This study used embryos reared from oocytes enriched with cortisol and the glucocorticoid receptor (GR) antagonist, RU486, to determine whether the growth-promoting actions of cortisol involve GR protein activation and modulation of gr expression. Whole-mount in situ immunohistofluorescence studies of zygotes showed that enhanced oocyte cortisol increased the immunofluorescent GR signal and activated the relocation of GR from a general distribution throughout the cytoplasm to an accumulation in the peri-nuclear cytoplasm. In ovo cortisol treatment increased the number of embryonic cells within 48-h post-fertilization, and RU486 partially suppressed this cortisol stimulation of cell duplication. In addition, there was complex interplay between the expression of gr and igf system related genes spatiotemporally in the different treatment groups, suggesting a role for GR in the regulation of the expression of development. Taken together, these findings indicate an essential role for GR in the regulation of epigenomic events in very early embryos that promoted the long-term growth effects of the embryos and juvenile fish. Moreover, the pretreatment of the oocyte with RU486 had a significant suppressive effect on the maternal mRNA transcript number of gr and igf system-related genes in oocytes and very early stage embryos, suggesting an action of antagonist on the stability of the maternal transcriptome. PMID- 22782384 TI - 3 Different types of strength training in older women. AB - The objective of the present study was to evaluate and compare the neuromuscular, morphological and functional adaptations of older women subjected to 3 different types of strength training. 58, healthy women (67 +/- 5 year) were randomized to experimental (EG, n=41) and control groups (CG, n=17) during the first 6 weeks when the EG group performed traditional resistance exercise for the lower extremity. Afterwards, EG was divided into three specific strength training groups; a traditional group (TG, n=14), a power group (PG, n=13) that performed the concentric phase of contraction at high speed and a rapid strength group (RG, n=14) that performed a lateral box jump exercise emphasizing the stretch shortening-cycle (SSC). Subjects trained 2 days per week through the entire 12 weeks. Following 6 weeks of generalized strength training, significant improvements occurred in EG for knee extension one-repetition (1RM) maximum strength (+19%), knee extensor muscle thickness (MT, +15%), maximal muscle activation (+44% average) and onset latency ( -31% average) for vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) compared to CG (p<0.05). Following 6 more weeks of specific strength training, the 1RM increased significantly and similarly between groups (average of +21%), as did muscle thickness of the VL (+25%), and activation of VL (+44%) and VM (+26%). The onset latency of RF (TG=285 +/- 109 ms, PG=252 +/- 76 ms, RG=203 +/- 43 ms), reaction time (TG=366 +/- 99 ms, PG=274 +/- 76 ms, RG=201 +/- 41 ms), 30-s chair stand (TG=18 +/- 3, PG=18 +/- 1, RG=21 +/- 2) and counter movement jump (TG=8 +/- 2 cm, PG=10 +/- 3 cm, RG=13 +/- 2 cm) was significantly improved only in RG (p<0.05). At the end of training, the rate of force development (RFD) over 150 ms (TG=2.3 +/- 9.8 N.s(-1), PG=3.3 +/- 3.2 N.s(-1), RG=3.8 +/- 6.8 N.s(-1), CG=2.3 +/- 7.0 N.s(-1)) was significantly greater in RG and PG than in TG and CG (p<0.05). In conclusion, rapid strength training is more effective for the development of rapid force production of muscle than other specific types of strength training and by consequence, better develops the functional capabilities of older women. PMID- 22782386 TI - Combined strength and endurance training improves health-related quality of life in healthy middle-aged and older adults. AB - The purpose of this study was to evaluate the effects of 21 weeks of strength and/or endurance training on health related quality of life (HRQoL) in 39-77 year old healthy subjects. 108 men and 96 women were randomized into endurance, strength, or combined training groups and controls. Strength-group performed high intensity strength training while endurance-group performed cycle training. Combined-group completed both training protocols. Leg extension strength and maximal oxygen uptake were measured. HRQoL was assessed with a Finnish version of SF-36 questionnaire. A significant training-induced difference was observed between groups (p=0.038) in the vitality dimension of HRQoL, which was characterized by a 6.6 +/- 1.5 unit increase in the combined group and no change in the other groups. Both endurance and combined training showed small improvements in certain dimensions of HRQoL. Dimensions of general (4.6 +/- 1.9) and mental health (3.9 +/- 1.4) improved in combined-group while general health (4.4 +/- 2.0), bodily pain (5.5 +/- 2.5) and role physical (6.0 +/- 2.4) improved in endurance-group. Strength-group experienced increased pain ( -5.4 +/- 1.8) during the experimental period. However, increased perception of pain was not observed during combined training. According to the present results both endurance and especially combined training may have potential to promote or maintain certain dimensions of HRQoL even in middle-aged and older adults. PMID- 22782385 TI - Urine and serum concentrations of inhaled and oral terbutaline. AB - We examined urine and serum concentrations after therapeutic use of single and repetitive doses of inhaled and supratherapeutic oral use of terbutaline. We compared the concentrations in 10 asthmatics and 10 healthy subjects in an open label, cross-over study with 2 mg inhaled and 10 mg oral terbutaline on 2 study days. Further, 10 healthy subjects were administrated 1 mg inhaled terbutaline in 4 repetive doses with total 4 mg. Blood samples were collected at baseline and during 6 h after the first inhalations. Urine samples were collected at baseline and during 12 h after the first inhalations. Median (IQR) urine concentrations peaked in the period 0-4 h after inhalation with Cmax 472 (324) ng/mL in asthmatics and 661 (517) ng/mL in healthy subjects, and 4-8 h after oral use with Cmax 666 (877) ng/mL in asthmatic and 402 (663) ng/mL in healthy subjects. In conclusion we found no significant differences in urine and serum concentrations between asthmatic and healthy subjects. We compared urine and serum concentrations after therapeutic inhaled doses and supratherapeutic oral doses and observed significant statistical differences in both groups but found it impossible to distinguish between therapeutic and prohibited use based on doping tests with urine and blood samples. PMID- 22782387 TI - Time of day effects on repeated sprint ability. AB - The present study aimed at investigating the effects of time-of-day on muscle power and associated electromyographic (EMG) activity level of 4 thigh muscles during a repeated pedalling sprint exercise. After a familiarization session, 12 male subjects were asked to perform the repeated sprint ability test during 2 experimental sessions (randomized order), which were set up either at 06:00 or 18:00 h. For each sprint, peak power output, percentage of peak power decrement and total work were calculated. EMG activity of vastus lateralis, rectus femoris, vastus medialis and biceps femoris muscles was recorded throughout the test and analyzed for each sprint. Total work and percentage of peak power decrement were higher in the evening than in the morning (p<0.01 and p<0.05, respectively). Likewise, peak power was significantly higher at 18:00 than 06:00 h during the first 3 sprints (p<0.01 for sprint 1 and p<0.05 for sprint 2 and 3). There was no time-of-day effect for EMG activity level. The neuromuscular efficiency decreased significantly over the repeated sprint ability test at the 2 times of testing (p<0.01). Despite diurnal fluctuation in muscular power and neuromuscular fatigue during the repeated sprint ability test, EMG activity of major thigh muscles was not time-of-day dependent. PMID- 22782390 TI - The cover. The Spanish boat. PMID- 22782393 TI - CMS seeks to reduce antipsychotic use in nursing home residents with dementia. PMID- 22782394 TI - Study: Acute coronary events linked with PTSD. PMID- 22782400 TI - Stem cell therapy in kidney transplantation. PMID- 22782402 TI - Lipid parameters and cardiovascular events in patients taking statins. PMID- 22782403 TI - Lipid parameters and cardiovascular events in patients taking statins. PMID- 22782405 TI - Shortening medical education. PMID- 22782406 TI - Shortening medical education. PMID- 22782407 TI - Shortening medical education. PMID- 22782408 TI - Shortening medical education. PMID- 22782409 TI - Shortening medical education. PMID- 22782412 TI - The moral duty to buy health insurance. PMID- 22782413 TI - Patient satisfaction and patient-centered care: necessary but not equal. PMID- 22782414 TI - Eliminating the use of partially hydrogenated oil in food production and preparation. PMID- 22782415 TI - A piece of my mind. Learning to talk. PMID- 22782417 TI - Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial. AB - CONTEXT: Ischemia/reperfusion injury remains an important cause of morbidity and mortality after coronary artery bypass graft (CABG) surgery. In a meta-analysis of randomized controlled trials, perioperative and postoperative infusion of acadesine, a first-in-class adenosine-regulating agent, was associated with a reduction in early cardiac death, myocardial infarction, and combined adverse cardiac outcomes in participants undergoing on-pump CABG surgery. OBJECTIVE: To assess the efficacy and safety of acadesine administered in the perioperative period in reducing all-cause mortality, nonfatal stroke, and severe left ventricular dysfunction (SLVD) through 28 days. DESIGN, SETTING, AND PARTICIPANTS: The Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG (RED-CABG) trial, a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate- to high-risk patients (median age, 66 years) undergoing nonemergency, on-pump CABG surgery at 300 sites in 7 countries. Enrollment occurred from May 6, 2009, to July 30, 2010. INTERVENTIONS: Eligible participants were randomized 1:1 to receive acadesine (0.1 mg/kg per minute for 7 hours) or placebo (both also added to cardioplegic solutions) beginning just before anesthesia induction. MAIN OUTCOME MEASURE: Composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD during and following CABG surgery through postoperative day 28. RESULTS: Because results of a prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome, the trial was stopped after 3080 of the originally projected 7500 study participants were randomized. The primary outcome occurred in 75 of 1493 participants (5.0%) in the placebo group and 76 of 1493 (5.1%) in the acadesine group (odds ratio, 1.01 [95% CI, 0.73-1.41]). There were no differences in key secondary end points measured. CONCLUSION: In this population of intermediate- to high-risk patients undergoing CABG surgery, acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or SLVD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00872001. PMID- 22782418 TI - Risk of adverse fetal outcomes following administration of a pandemic influenza A(H1N1) vaccine during pregnancy. AB - CONTEXT: Assessment of the fetal safety of vaccination against influenza A(H1N1)pdm09 in pregnancy has been limited. OBJECTIVE: To investigate whether exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of adverse fetal outcomes. DESIGN, SETTING, AND PARTICIPANTS: Registry-based cohort study based on all liveborn singleton infants in Denmark, delivered between November 2, 2009, and September 30, 2010. In propensity score-matched analyses, we estimated prevalence odds ratios (PORs) of adverse fetal outcomes, comparing infants exposed and unexposed to an AS03 adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy. MAIN OUTCOME MEASURES: Major birth defects, preterm birth, and small size for gestational age. RESULTS: From a cohort of 53,432 infants (6989 [13.1%] exposed to the influenza A[H1N1]pdm09 vaccine during pregnancy [345 in the first trimester and 6644 in the second or third trimester]), 660 (330 exposed) were included in propensity score matched analyses of adverse fetal outcomes associated with first-trimester exposure. For analysis of small size for gestational age after second- or third trimester exposure, 13,284 (6642 exposed) were included; for analyses of preterm birth, 12,909 (6543 exposed) were included. A major birth defect was diagnosed in 18 of 330 infants (5.5%) exposed to the vaccine in the first trimester, compared with 15 of 330 unexposed infants (4.5%) (POR, 1.21; 95% CI, 0.60-2.45). Preterm birth occurred in 31 of 330 infants (9.4%) exposed in the first trimester, compared with 24 of 330 unexposed infants (7.3%) (POR, 1.32; 95% CI, 0.76-2.31), and in 302 of 6543 infants (4.6%) with second- or third-trimester exposure, compared with 295 of 6366 unexposed infants (4.6%) (POR, 1.00; 95% CI, 0.84 1.17). Small size for gestational age was observed in 25 of 330 infants (7.6%) with first-trimester exposure compared with 31 of 330 unexposed infants (9.4%) (POR, 0.79; 95% CI, 0.46-1.37), and in 641 of 6642 infants (9.7%) with second- or third-trimester exposure, compared with 657 of 6642 unexposed infants (9.9%) (POR, 0.97; 95% CI, 0.87-1.09). CONCLUSIONS: In this Danish cohort, exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was not associated with a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction. PMID- 22782420 TI - A pain in the neck. PMID- 22782419 TI - Risk of Guillain-Barre syndrome following H1N1 influenza vaccination in Quebec. AB - CONTEXT: In fall 2009 in Quebec, Canada, an immunization campaign was launched against the 2009 influenza A(H1N1) pandemic strain, mostly using an AS03 adjuvant vaccine. By the end of the year, 57% of the 7.8 million residents had been vaccinated. OBJECTIVE: To assess the risk of Guillain-Barre syndrome (GBS) following pandemic influenza vaccine administration. DESIGN: Population-based cohort study with follow-up over the 6-month period October 2009 through March 2010. The investigation was ordered by the chief medical officer of health in accordance with the Quebec Public Health Act. SETTING: All acute care hospitals and neurology clinics in Quebec. POPULATION: Suspected and confirmed GBS cases reported by physicians, mostly neurologists, during active surveillance or identified in the provincial hospital summary discharge database. Medical records were reviewed and cases classified according to Brighton Collaboration definitions (categorized as level 1, 2, or 3, corresponding to criteria of decreasing certainty in diagnosis). Immunization status was verified and denominators were estimated from the provincial immunization registry (4.4 million vaccinated) and census data (total target population aged >=6 months, 7.8 million), with a total of 3,623,046 person-years of observation. MAIN OUTCOME MEASURES: Relative and attributable risks were calculated using a Poisson model and the self-controlled case-series method. RESULTS: Over a 6-month period, 83 confirmed GBS cases were identified, including 71 Brighton level 1 through 3 cases. Twenty-five confirmed cases had been vaccinated against 2009 influenza A(H1N1) 8 or fewer weeks before disease onset, with most (19/25) vaccinated 4 or fewer weeks before onset. In the Poisson model, the age- and sex-adjusted relative risk was 1.80 (95% CI, 1.12-2.87) for all confirmed cases during the 8 week postvaccination period and was 2.75 (95% CI, 1.63-4.62) during the 4-week postvaccination period. Using the self-controlled case-series method, relative risk estimates during the 4-week postvaccination period were 3.02 (95% CI, 1.64 5.56) for all confirmed cases (n = 42) and 2.33 (95% CI, 1.19-4.57) for Brighton level 1 through 3 cases (n = 36). The number of GBS cases attributable to vaccination was approximately 2 per 1 million doses. There was no indication of an excess risk in persons younger than 50 years. CONCLUSIONS: In Quebec, the 2009 influenza A(H1N1) vaccine was associated with a small but significant risk of GBS. It is likely that the benefits of immunization outweigh the risks. PMID- 22782421 TI - Influenza pandemics--pregnancy, pathogenesis, and perinatal outcomes. PMID- 22782425 TI - JAMA patient page. Hospice care. PMID- 22782416 TI - Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. AB - CONTEXT: Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas. OBJECTIVE: To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection. DESIGN, SETTING, AND PATIENTS: The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers. INTERVENTIONS: One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life. RESULTS: Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; chi2 = 1.33; P = .25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald chi2 = 4.53, P = .03). CONCLUSIONS: Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201. PMID- 22782426 TI - Massive rotator cuff tear associated with acute traumatic posterior shoulder dislocation: report of two cases and literature review. AB - A massive rotator cuff tear in association with acute traumatic posterior glenohumeral dislocation is rare. To our knowledge, only four documented cases have been reported in the literature. We present two additional cases of such injury secondary to the traffic accident. The first patient had an unsuccessful closed reduction due to the posterior instability while the second developed the profound shoulder weakness following the reduction. From the findings of our cases together with the previous reports, every patient had a unique injury mechanism of high-energy directed axial loading on an outstretched, adducted, and internally rotated arm. The glenohumeral capsule and rotator cuff were uniformly avulsed from the humeral attachment, and the supraspinatus and infraspinatus were always involved. However, the clinical presentations were variable based on the severity of the associated rotator cuff tear. The outcomes of operative treatment in this type of injury with the open repair were favorable. PMID- 22782427 TI - The asthma awareness patch program for Girl Scouts: an evaluation of educational effectiveness. AB - BACKGROUND: Carefully designed educational programs can improve asthma knowledge, management practices, and health outcomes. We used pre-post testing to determine if the curriculum provided in the Girl Scouts of the USA Asthma Awareness Patch Program improved recipients' knowledge of basic respiratory system function, asthma pathophysiology, triggers, and asthma exacerbation recognition and management. We hypothesized that participants would have improved post-test scores following an interactive asthma educational program. METHODS: Girl Scouts ages 5-17 years from a 4-county area in northeastern Ohio were recruited. Educational components were in compliance with the guidelines established by the National Heart, Lung, and Blood Institute's National Asthma Education and Prevention Program. Participants completed a demographic form and pre-test before, and a post-test and program evaluation immediately following, the program. Descriptive statistics were used to report participant demographics. Frequencies and percentages described the participants' responses to pre- and post-test questions. Cronbach's alpha analysis determined internal consistency and reliability of post-test items. T tests assessed differences in pre-post scores. Fishers exact tests determined differences in proportions of responses, between the pre- and post-test time points. A P value of < 0.05 was considered statistically significant. RESULTS: Eighty-six girls, between 5 and 16 years of age (mean +/- SD 8.97 +/- 2.36 y) participated, 84% of whom were white. Twenty one percent of the participants were diagnosed and treated for asthma, 48% resided with an asthmatic, and 72% knew someone with asthma. The post-test scores (mean +/- SD 89.6 +/- 9.0) were significantly higher (P < .001) than the pre-test scores (62.5 +/- 20.8). A Cronbach alpha raw score of 0.448 and a standardized score of 0.518 were realized. CONCLUSIONS: The assessment tool demonstrated moderate internal reliability. Participation in the program enhanced participants' knowledge of lung function, trigger identification, asthma pathophysiology, and treatment. PMID- 22782428 TI - The many domains of TFPI. PMID- 22782429 TI - Novel intercluster compound between a heptakis{triphenylphosphinegold(I)}dioxonium cation and an alpha-Keggin polyoxometalate anion. AB - A novel intercluster compound, [{{Au(PPh(3))}(4)(MU(4)-O)}{{Au(PPh(3))}(3)(MU(3) O)}][alpha-PW(12)O(40)].EtOH (1) constructed between a heptakis{triphenylphosphinegold(i)}dioxonium cation and an alpha-Keggin polyoxometalate (POM) is synthesized and unequivocally characterized by elemental analysis, TG/DTA, FTIR, X-ray crystallography, solid-state CPMAS (31)P NMR and solution ((1)H, (31)P{(1)H}) NMR. The heptagold(i) cluster was formed during the course of carboxylate elimination of a monomeric phosphinegold(i) carboxylate precursor, i.e., [Au((RS)-pyrrld)(PPh(3))] ((RS)-Hpyrrld = (RS)-2-pyrrolidone-5 carboxylic acid), in the presence of the sodium salt of an alpha-Keggin POM, Na(3)[alpha-PW(12)O(40)].9H(2)O. Compound 1 was formed by ionic interaction between the heptagold(i) cluster cation and the alpha-Keggin POM anion. The heptagold(i) cluster unit was formed by four inter-cationic aurophilic interactions between the tetragold(i) cluster unit and trigold(i) cluster unit. The tetragold(i) cluster unit and trigold(i) cluster unit contained MU(4)-O and MU(3)-O atoms, respectively. PMID- 22782430 TI - A simple linear model for estimating ozone AOT40 at forest sites from raw passive sampling data. AB - A rapid, empirical method is described for estimating weekly AOT40 from ozone concentrations measured with passive samplers at forest sites. The method is based on linear regression and was developed after three years of measurements in Trentino (northern Italy). It was tested against an independent set of data from passive sampler sites across Italy. It provides good weekly estimates compared with those measured by conventional monitors (0.85 <=R(2)<= 0.970; 97 <= RMSE <= 302). Estimates obtained using passive sampling at forest sites are comparable to those obtained by another estimation method based on modelling hourly concentrations (R(2) = 0.94; 131 <= RMSE <= 351). Regression coefficients of passive sampling are similar to those obtained with conventional monitors at forest sites. Testing against an independent dataset generated by passive sampling provided similar results (0.86 <=R(2)<= 0.99; 65 <= RMSE <= 478). Errors tend to accumulate when weekly AOT40 estimates are summed to obtain the total AOT40 over the May-July period, and the median deviation between the two estimation methods based on passive sampling is 11%. The method proposed does not require any assumptions, complex calculation or modelling technique, and can be useful when other estimation methods are not feasible, either in principle or in practice. However, the method is not useful when estimates of hourly concentrations are of interest. PMID- 22782431 TI - Meta-analysis of the association between angiotensin II receptor, type 1 gene A1166C polymorphism and coronary artery disease in Chinese populations. AB - BACKGROUND: and objective: Many studies have examined the association between the angiotensin II receptor, type 1 (AGTR1) gene A1166C polymorphism and coronary artery disease (CAD); the results, however, remain controversial. Given the accumulation of data, we conducted a meta-analysis of published studies on this association in Chinese. METHODS: and results: A comprehensive search of PubMed, Wanfang and Chinese National Knowledge Infrastructure (CNKI) databases was conducted before January 2012. Data and study quality were assessed in duplicate. Twenty-two studies totaling 3502 CAD patients and 3071 controls were analyzed. Overall, individuals carrying 1166C allele had a remarkably increased risk of CAD compared with those with 1166AA genotype (odds ratio (OR)=1.63; 95% confidence interval (CI): 1.26-2.1; P<0.0005). In subgroup analyses by geography, the risk magnitude was slightly augmented in northern Chinese (OR=1.76; 95% CI: 1.23-2.52; P=0.002) relative to in southern Chinese (OR=1.55; 95% CI: 1.13-2.14; P=0.007). Grouping studies by average age detected a strong association in studies involving CAD patients aged >= 60 years. Differences in the diagnosis of CAD and source of controls might be potential sources of between-study heterogeneity. CONCLUSIONS: Our findings provided strong evidence that AGTR1 gene A1166C polymorphism might be a genetic marker for the development of CAD in Chinese populations, especially in the context of studies with northern and older subjects. PMID- 22782433 TI - Death, cadavers and post-mortem biomedical research: a point of view from a Christian community. AB - Facing modern developments of medicine and biomedical researches, religious communities are a strong source of ethics principles and orientations. Human dignity does not disappear after life, in a context of biomedical research on cadavers. Moral, political, social and scientific aspects of research on human cadavers (mainly autopsies) have been widely discussed in biomedical publications, whereas the religious ones (which could be predominant for some) have rarely been analyzed and presented. This article will present the results of a survey carried out a French Benedictine Abbey (relative to death, cadaver's status and biomedical research) and subsequent Christian background according to canonic texts and practical cases from anthropological, historical, archeological and biomedical origin. PMID- 22782432 TI - Human middle longitudinal fascicle: variations in patterns of anatomical connections. AB - Based on high-resolution diffusion tensor magnetic resonance imaging (DTI) tractographic analyses in 39 healthy adult subjects, we derived patterns of connections and measures of volume and biophysical parameters, such as fractional anisotropy (FA) for the human middle longitudinal fascicle (MdLF). Compared to previous studies, we found that the cortical connections of the MdLF in humans appear to go beyond the superior temporal (STG) and angular (AG) gyri, extending to the temporal pole (TP), superior parietal lobule (SPL), supramarginal gyrus, precuneus and the occipital lobe (including the cuneus and lateral occipital areas). Importantly, the MdLF showed a striking lateralized pattern with predominant connections between the TP, STG and AG on the left and TP, STG and SPL on the right hemisphere. In light of the results of the present study, and of the known functional role of the cortical areas interconnected by the MdLF, we suggested that this fiber pathway might be related to language, high order auditory association, visuospatial and attention functions. PMID- 22782434 TI - The emotional impact of bullying and cyberbullying on victims: a European cross national study. AB - Past research has demonstrated the effects of bullying can be severe and long term for the individuals involved. The main aim of this study is to analyze the emotional impact on victims of traditional bullying, both direct and indirect forms, and of cyberbullying through mobile phones and the Internet. A sample of 5,862 adolescents from three different countries, Italy (N = 1,964), Spain (N = 1,671), and England (N = 2,227), responded to a questionnaire that asked if they had experience of various forms of bullying, and the consequent emotional impact. The results show that both traditional bullying and cyberbullying have a significant prevalence in the samples. Emotional responses are linked to types of bullying. Analysis of answers identified specific emotional profiles for the different types of bullying and cyberbullying. Direct bullying and cyberbullying via mobile phone showed similar profiles, and also indirect bullying and cyberbullying using the Internet. Similarities and differences between profiles are discussed and some hypotheses are presented to explain the results. In addition, school grade, gender, country, and severity of bullying episodes were related to the specific emotional profiles of each type of bullying. PMID- 22782435 TI - PEI/DNA formation affects transient gene expression in suspension Chinese hamster ovary cells via a one-step transfection process. AB - Polyethylenimine (PEI) has been used widely in transient gene expression studies of mammalian cells. We performed transient gene expression in suspension Chinese hamster ovary cells using a one-step transfection procedure in which DNA and PEI were simultaneously added to a cell culture in suspension without prior PEI/DNA complex incubation. To further understand the effect of PEI/DNA formation on the transfection and expression of exogenous gene in shaking state, we investigated the diameter and overcharge of the PEI/DNA complex. The results showed that the diameter of the complex was smaller with more positive charge when the PEI/DNA ratio was higher. Moreover, DNA more easily penetrated cells and nuclei at higher PEI concentrations. The highest transcription level, transfection efficiency, and GFP expression were obtained when the PEI/DNA ratio was 5:1. PMID- 22782437 TI - Volatile organic compound analysis by ion molecule reaction mass spectrometry for Gram-positive bacteria differentiation. AB - Approximately 50 % of all clinically proven infections in critically ill patients are caused by Gram-positive bacteria. The timely and appropriate treatment of these infections is vital in order to avoid negative outcomes. Hence, fast and reliable methods are needed for the early detection and identification of microorganisms. Recently, direct mass spectrometry-based analysis of volatile organic compounds emitted by microorganisms has been employed to study Gram negative bacteria. Here, we report a feasibility study of ion molecule reaction mass spectrometry (IMR-MS) for in vitro growth detection and species differentiation of selected Gram-positive bacteria that are frequently isolated in blood culture samples, namely, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Staphylococcus epidermidis. Ion molecule reaction mass spectrometry was used to analyze the headspace above cultures containing Gram positive bacteria incubated at 37 degrees C starting with 10(2) colony-forming units (CFU)/ml. Measurements to determine the presence of volatile organic compounds were performed 4, 8, and 24 h after incubation, respectively. The detection of microbial growth was accomplished already after 8 h in cultures containing E. faecalis. After 24 h of incubation, characteristic mass spectra were obtained for all species. Processing these mass spectra by hierarchic clustering and principal component analysis (PCA) enabled us to differentiate between bacterial species. IMR-MS in conjunction with a cumulative end-point model provides the means for rapid growth detection and differentiation of Gram positive bacteria on the species level, typically within an analysis time of less than 3 min per sample. PMID- 22782438 TI - Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial. AB - Early evidence suggests the efficacy of voriconazole for chronic pulmonary aspergillosis (CPA). We conducted a prospective, open, multicenter trial to evaluate the efficacy and safety of voriconazole for proven CPA in minimally or non-immunocompromised patients. Patients had CPA confirmed by chest computed tomography (CT) and/or endoscopy, positive Aspergillus culture from a respiratory sample, and positive serologic test for Aspergillus precipitins. Patients received voriconazole (200 mg twice daily) for a period of 6-12 months and were followed for 6 months after the end of therapy (EOT). The primary endpoint was global success at 6 months, defined as complete or partial (>=50 % improvement) radiological response and mycological eradication. Forty-one patients with confirmed CPA were enrolled. All patients had A. fumigatus as the etiologic agent. By EOT, five patients had died from comorbidities and seven had discontinued voriconazole due to toxicity. The global success rate at 6 months was 13/41 (32 %): 10/19 (53 %) for chronic necrotizing aspergillosis and 3/22 (14 %) for chronic cavitary aspergillosis (p = 0.01). The respective success rates at EOT were 58 and 32 %. Clinical symptoms and quality of life also improved during treatment. Voriconazole is effective for CPA, with acceptable toxicity. The response rate is higher and obtained more rapidly in necrotizing than cavitary forms. PMID- 22782439 TI - Whole report uncovers correctly identified but incorrectly placed target information under visual crowding. AB - Multiletter identification studies often find correctly identified letters being reported in wrong positions. However, how position uncertainty impacts crowding in peripheral vision is not fully understood. The observation of a flanker being reported as the central target cannot be taken as unequivocal evidence for position misperception because the observers could be biased to report a more identifiable flanker when failing to identify the central target. In addition, it has never been reported whether a correctly identified central target can be perceived at a flanker position under crowding. Empirical investigation into this possibility holds the key to demonstrating letter-level position uncertainty in crowding, because the position errors of the least identifiable central target cannot be attributed to response bias. We asked normally-sighted observers to report either the central target of a trigram (partial report) or all three characters (whole report). The results showed that, for radially arranged trigrams, the rate of reporting the central target regardless of the reported position in the whole report was significantly higher than the partial report rate, and the extra target reports mostly ended up in flanker positions. Error analysis indicated that target-flanker position swapping and misalignment (lateral shift of the target and one flanker) underlay this target misplacement. Our results thus establish target misplacement as a source of crowding errors and ascertain the role of letter-level position uncertainty in crowding. PMID- 22782440 TI - Surgical outcomes after resection of both hepatic and pulmonary metastases from colorectal cancer. AB - BACKGROUND: The efficacy and the indications of resection of synchronous or metachronous hepatic and pulmonary metastases from colorectal cancer (CRC) are controversial. This study retrospectively reviewed the cases of CRC patients who underwent both liver and lung resection to define the appropriate indications for surgical resection in patients with hepatic and pulmonary metastases. METHODS: A total of 39 patients with both hepatic and pulmonary metastases from CRC underwent both liver and lung resection from January 1987 to December 2009. The relapse-free survival (RFS) and overall survival (OS) from the resection for the first metastasis were evaluated by a Kaplan-Meyer analysis. Prognostic factors were analyzed using the log-rank test and a Cox proportional hazards model. RESULTS: The median RFS and the 5-year RFS rate of all patients were 12 months and 2.6 %, respectively. The median survival time (MST) and 5-year OS rate of all patients were 66 months and 48.3 %, respectively. The MST of the patients with a long (>1 year) disease-free interval (DFI) could not be calculated, but their 5 year OS rate was 73.7 %. In contrast, the MST and 5-year OS rate of the patients with a short (<1 year) DFI were 29 months and 37.5 %, respectively. The short DFI was the only prognostic factor in the multivariate analysis. CONCLUSIONS: Aggressive surgical resection of both hepatic and pulmonary metastases from CRC should be undertaken in selective patients, including those with a long DFI. PMID- 22782441 TI - Surgical reoxygenation injury of the myocardium in cyanotic patients: clinical relevance and therapeutic strategies by normoxic management during cardiopulmonary bypass. AB - Cyanotic hearts are associated with depleted endogenous antioxidants (glutathione peroxidase, superoxide dismutase, and catalase), and thereby is more susceptible to myocardial ischemia/reperfusion injury during open heart surgery compared with acyanotic ones. Clinically, when surgery is performed on cyanotic infants, cardiopulmonary bypass (CPB) is usually initiated at high PaO(2), without consideration of possible cytotoxic effects of hyperoxia. The concept of "surgical reoxygenation injury of cyanotic myocardium" was proposed, wherein unintended abrupt reoxygenation of cyanotic myocardium at the onset of routine CPB causes oxygen-mediated injury, which may render the reoxygenated myocardium more susceptible to subsequent surgical ischemia/reperfusion injury and accentuates post-CPB myocardial dysfunction. The experimental studies using acute and chronic hypoxia models confirmed the role of reoxygenation injury mediated by reactive oxygen species in the pathogenesis of post-CPB myocardial dysfunction and addressed the importance of controlling PaO(2) at the onset of CPB. The clinical relevance of this injury was shown by subsequent clinical studies, which demonstrated depleted antioxidant reserve capacity and troponin release during the initial reoxygenation on hyperoxic CPB prior to cardioplegic arrest. Furthermore recent randomized clinical trials verified that hyperoxic CPB provokes biochemical multi-organ damage including myocardium, lung, liver, and brain after open heart surgery in cyanotic patients, which can be successfully reduce by normoxic CPB management (i.e., reducing PaO(2) at onset of CPB, gradual reoxygenation and controlled reoxygenation protocol). Based on these experimental and clinical studies, avoidance of using hyperoxic PaO(2) on routine CPB is strongly recommended in the cyanotic patients. PMID- 22782442 TI - Use of Venturi effect for effective and uniform talc pleurodesis. PMID- 22782443 TI - Stabilisation of cardiopulmonary function in newborns with congenital diaphragmatic hernia using lung function parameters and hemodynamic management. AB - OBJECTIVE: Evaluation of lung function parameters and additional use of prostaglandin E1 (PGE1) for the stabilisation of cardiopulmonary function in patients with congenital diaphragmatic hernia (CDH) and pulmonary hypertension (PHT). DESIGN: Observational study. PATIENTS: Between 2007 and 2009 8 patients with CDH have been treated in our pediatric intensive care unit (gestational age 34 + 0 - 40 + 4 weeks, birth weight 2 160-3 840 g). All patients required respiratory support. Gentle mechanical ventilation adapted to the degree of pulmonary hypoplasia based on serially measurements of lung function parameters to find appropriate ventilator settings has been performed. MAIN RESULTS: Functional residual capacity (FRC) and compliance of the respiratory system in all patients were markedly reduced. A FRC between 9.3-10.6 ml/kg and compliance between 1.1-1.8 ml/kPa/kg indicated pronounced hypoplasia of the lungs. Doppler flow patterns through the arterial duct were classified into left-to-right, right to-left and bidirectional shunting and correlated to the degree of PHT. The additional use of PGE1 to reopen the arterial duct and to stabilize right ventricular function led to an amelioration of severe PHT and preoperative stabilisation in 2 newborns with pronounced pulmonary hypoplasia. All patients underwent successful surgery, and did not show any complications after 2 years follow-up. CONCLUSION: Measurements of lung function parameters and adaptation of mechanical ventilation to the degree of pulmonary hypoplasia and additional therapy with PGE1 may help to improve the outcome in CDH patients. PMID- 22782444 TI - A regioselective Huisgen reaction inside a Keplerate polyoxomolybdate nanoreactor. AB - A 1,3-dipolar cycloaddition reaction taking place quantitatively between propiolic acid "guests" and azide functions previously attached to binding sites within the cavity of a {Mo(132)}-type Keplerate reproducibly gives a 2 : 1 ratio of 1,4- and 1,5-triazoles. PMID- 22782445 TI - Indirect comparison studies--are they useful? Insights from the novel oral anticoagulants for stroke prevention in atrial fibrillation. PMID- 22782446 TI - Clinical and biological implications of the tumor microenvironment. AB - In normal tissues and organs, the activities of the constituent cells are strictly restricted to the tasks assigned to them during development. In addition they (with the exception of leukocytes) remain inflexibly confined to their territorial domains by regulatory interactions with their neighbors.This creates specialized local micro-environments in which structure and function are orderly, stable and tightly controlled by feed-back loops, within interacting regulatory networks.This system has considerable ability to adapt to changing conditions. In contrast, the microenvironment in regions where tumors are forming and expanding is characterized by progressive loss of specialized or differentiated cellular functions,disorderly molecular signals, and degeneration of microscopical organ structure. This, coupled with the traffic of cells into and out of the tumor, often culminates in local invasion and metastasis to other organs. The nature of these disturbed molecular and cellular interactions is, by definition,highly unstable and increasingly unpredictable as time passes.It also varies between different tumors, sometimes even leading to regression. However, systematic analysis of this dysfunction in the tumor microcosm, using multiple modern research techniques, has revealed that all actively growing primary and secondary neoplasms share an absolute dependency upon support from adjacent non-neoplastic cells of the host. This support, in turn, continuously depends upon dynamic interplay between tumor and host cell populations, via signaling molecules and surface receptors in the tumor microenvironment.Such interplay determines the fate of the growing neoplasm. Such information, described and evaluated in this article, provides important new insights into the etiology of carcinogenesis and how tumor growth, invasion and metastasis might be therapeutically arrested. The facts and concepts assembled below, regarding the cancer microenvironment, demonstrate how modern molecular findings reveal the impact of the wide range of cancer diseases upon the internal cellular, tissue and organ environments of the whole individual and how this applies to designing new work to improve human cancer diagnosis and treatment. The article discusses several specific types of experimentally-induced and clinically common cancers to derive principles useful for interpreting events in the tumor microenvironment,which apply to cancers in general and especially to human malignant disease. PMID- 22782447 TI - No difference in survivorship after unicompartmental knee arthroplasty with or without an intact anterior cruciate ligament. AB - PURPOSE: Anterior cruciate ligament deficiency (ACLD) has been considered a contraindication for Oxford unicompartmental knee arthroplasty (UKA) because of the reported higher incidence of failure when implanted in ACLD knees. However, given the potential advantages of UKA over total knee arthroplasty (TKA), we have performed UKA in a limited number of patients with ACL deficiency and end-stage medial compartment osteoarthritis (OA) over the past 11 years. The primary aim of this study was to establish the clinical outcome of this cohort; the secondary aim was to compare both clinical and radiographic data with a matched cohort of ACL-intact (ACLI) patients who have undergone UKA for anteromedial OA. METHODS: This retrospective observational study describes the clinical and radiological outcome in 46 medial Oxford UKAs implanted in 42 consecutive patients with ACL deficiency and concomitant symptomatic medial compartment OA at mean follow-up of 5 years. It also compares the outcomes with a matched cohort of UKA patients with an intact ACL (ACLI group). RESULTS: At the time of last follow-up, there was no significant difference in clinical results or survivorship between the two groups in this study. CONCLUSION: The successful short-term results of the ACLD group suggest ACL deficiency may not always be a contraindication to Oxford UKA as previously thought. Until long-term data is available, however, we maintain our recommendation that ACLD be considered a contraindication. PMID- 22782448 TI - Tendoscopic treatment of recurrent peroneal tendon dislocation. AB - PURPOSE: To study the possibility of tendoscopic treatment of recurrent peroneal tendon dislocation. METHODS: The case of one patient is described including the tendoscopic technique to deepen the fibular groove. RESULTS: In this single case, there were no complications, recovery time was short, and there was no recurrence of peroneal tendon dislocation. CONCLUSION: Though it seems possible to deepen the fibular groove tendoscopically, further studies are necessary to determine the role of tendoscopy in recurrent peroneal tendon dislocation. PMID- 22782449 TI - Blood separation on microfluidic paper-based analytical devices. AB - A microfluidic paper-based analytical device (MUPAD) for the separation of blood plasma from whole blood is described. The device can separate plasma from whole blood and quantify plasma proteins in a single step. The MUPAD was fabricated using the wax dipping method, and the final device was composed of a blood separation membrane combined with patterned Whatman No.1 paper. Blood separation membranes, LF1, MF1, VF1 and VF2 were tested for blood separation on the MUPAD. The LF1 membrane was found to be the most suitable for blood separations when fabricating the MUPAD by wax dipping. For blood separation, the blood cells (both red and white) were trapped on blood separation membrane allowing pure plasma to flow to the detection zone by capillary force. The LF1-MUPAD was shown to be functional with human whole blood of 24-55% hematocrit without dilution, and effectively separated blood cells from plasma within 2 min when blood volumes of between 15-22 MUL were added to the device. Microscopy was used to confirm that the device isolated plasma with high purity with no blood cells or cell hemolysis in the detection zone. The efficiency of blood separation on the MUPAD was studied by plasma protein detection using the bromocresol green (BCG) colorimetric assay. The results revealed that protein detection on the MUPAD was not significantly different from the conventional method (p > 0.05, pair t-test). The colorimetric measurement reproducibility on the MUPAD was 2.62% (n = 10) and 5.84% (n = 30) for within-day and between day precision, respectively. Our proposed blood separation on MUPAD has the potential for reducing turnaround time, sample volume, sample preparation and detection processes for clinical diagnosis and point-of care testing. PMID- 22782450 TI - Rational diagnostic strategies for Lyme borreliosis in children and adolescents: recommendations by the Committee for Infectious Diseases and Vaccinations of the German Academy for Pediatrics and Adolescent Health. AB - The varying clinical manifestations of Lyme borreliosis, transmitted by Ixodes ricinus and caused by Borrelia burgdorferi, frequently pose diagnostic problems. Diagnostic strategies vary between early and late disease manifestations and usually include serological methods. Erythema migrans is pathognomonic and does not require any further laboratory investigations. In contrast, the diagnosis of neuroborreliosis requires the assessment of serum and cerebrospinal fluid. Lyme arthritis is diagnosed in the presence of newly recognized arthritis and high titer serum IgG antibodies against B. burgdorferi. The committee concludes the following recommendations: Borrelial serology should only be ordered in case of well-founded clinical suspicion for Lyme borreliosis, i.e., manifestations compatible with the diagnosis. Tests for borrelial genomic sequences in ticks or lymphocyte proliferation assays should not be ordered. When results of such tests or of serological investigations that were not indicated are available, they should not influence therapeutic decisions. Laboratories should be cautious when interpreting results of serological tests and abstain from giving therapeutic recommendations and from proposing retesting after some time without intimate knowledge of patient's history and disease manifestations. PMID- 22782452 TI - New results for the formation of a muoniated radical in the Mu + Br2 system: a van der Waals complex or evidence for vibrational bonding in Br-Mu-Br? AB - New evidence is presented for the observation of a muoniated radical in the Mu + Br(2) system, from MUSR longitudinal field (LF) repolarisation studies in the gas phase, at Br(2) concentrations of 0.1 bar in a Br(2)/N(2) mixture at 300 K and at 10 bar total pressure. The LF repolarisation curve, up to a field of 4.5 kG, reveals two paramagnetic components, one for the Mu atom, formed promptly during the slowing-down process of the positive muon, with a known Mu hyperfine coupling constant (hfcc) of 4463 MHz, and one for a muoniated radical formed by fast Mu addition. From model fits to the Br(2)/N(2) data, the radical component is found to have an unusually high muon hfcc, assessed to be ~3300 MHz with an overall error due to systematics expected to exceed 10%. This high muon hfcc is taken as evidence for the observation of either the Br-Mu-Br radical, and hence of vibrational bonding in this H[combining low line]-L[combining low line] H[combining low line] system, or of a MuBr(2) van der Waals complex formed in the entrance channel. Preliminary ab initio electronic structure calculations suggest the latter is more likely but fully rigorous calculations of the effect of dynamics on the hfcc for either system have yet to be carried out. PMID- 22782451 TI - Sex ratio of infectious mononucleosis and possible relevance to multiple sclerosis. AB - Infectious mononucleosis (IM) is associated with the risk of developing multiple sclerosis (MS). Using databases of hospital admissions for England (1999-2005), we investigated the female-to-male ratios (FMRs) for admission to hospital for IM and MS stratified by age. Males were more frequently admitted for IM for all age groups apart from ages 10-14 (FMR 1.50; 95% confidence interval (CI) 1.36-1.64) and, borderline significantly, at ages 15-19 (FMR 1.03, 95% CI 0.99-1.08). This intriguing aspect of IM epidemiology in adolescence, the atypical female excess, may be linked to the sex ratio of MS, where females predominate from adolescence. PMID- 22782453 TI - Relationship between depression in patients with COPD and the percent of predicted FEV(1), BODE index, and health-related quality of life. AB - BACKGROUND: We investigated the prevalence of depression among patients with COPD treated in long-term in-patient rehabilitation facilities, using the Center for Epidemiologic Studies Depression scale (CES-D). Furthermore, the relationship between the severity of air-flow obstruction (the percent of predicted FEV(1)), BODE (body mass index, degree of air-flow obstruction, dyspnea, exercise capacity) index, health-related quality of life (St George's Respiratory Questionnaire [SGRQ]), and depression were investigated. METHODS: We recruited 74 in-patients (64 males, 10 females) with COPD. The mean age of the subjects was 72.7 years (range 52-85 y). Subjects completed the CES-D, and measurements were made of pulmonary function, body mass index, Modified Medical Research Council dyspnea scale, 6-min walk test (6MWT), and SGRQ. RESULTS: Depression was evident in 48.6% (n = 36) of the subjects. A weak correlation was found between the CES-D scores and the percent of predicted FEV(1). The prevalence of depression showed a significant association with BODE stage. Scores for the SGRQ activity and impacts domains, and total SGRQ score were significantly worse in the subjects who were depressed. CONCLUSIONS: We found a high prevalence of depression among patients with stable COPD treated in long-term in-patient rehabilitation facilities. Depression among these patients, as measured by the CES-D, was associated with greater impairment in respiratory function and with poorer Modified Medical Research Council dyspnea scale and SGRQ scores. The prevalence of depression increased with BODE stage. PMID- 22782454 TI - Optimization of a photopolymerizable material based on a photocyclic initiating system using holographic recording. AB - A set of photoinitiating systems (PIS) for free radical photopolymerization was studied using time-resolved spectroscopic experiments, real-time FTIR and holographic recording. It is shown that the efficiency of the photoinitiating system can be drastically increased when a redox additive is added to the conventional dye/coinitiator system by virtue of photocyclic behaviour. The homogeneous photopolymerization process was found to reach a fast vitrification, limiting the conversion at about 55%. By contrast, holographic recording underlines the differences in photoinitiating system reactivity, allowing diffraction efficiencies close to unity for the most reactive PIS. PMID- 22782455 TI - Increased expression and function of P-glycoprotein in peripheral blood CD56+ cells is associated with the chemoresistance of non-small-cell lung cancer. AB - PURPOSE: Chemoresistance is common among non-small-cell lung cancer (NSCLC), P glycoprotein (P-gp), encoded by the human multi-drug-resistant MDR1 gene, and multidrug-resistance protein 1 (MRP1) might be major contributors. The aim of the present study was to develop an effective method to investigate the expression and function of P-gp in the peripheral CD56+ cells in order to clarify their correlation with the chemoresistance in NSCLC. METHODS: Using microbead technology and a RT-qPCR methodology, we evaluated the expression levels of P-gp and MRP1 in the purified CD56+ cells in the chemoresistance and chemo-naive NSCLC patients compared with that in the healthy volunteers. Flow cytometric analysis was used to investigate the changes of P-gp function in the CD56+ cells between the three cohorts. RESULTS: The MDR1 gene expression was elevated markedly (twofold-tenfold), and P-gp function was increased in the chemoresistance cohort compared with the chemo-naive and the healthy cohorts; whereas there was only about two times averagely elevated for the MRP1 gene expression. No statistical significance (p > 0.05) was seen with respect to the expression of MDR1 and MRP1, the function of P-gp between the chemo-naive and the healthy cohorts. CONCLUSIONS: P-gp in peripheral CD56+ cells demonstrated possible clinical relevance as predictive biomarkers for the identification of chemoresistance in NSCLC, while MRP1 may not play a significant role in the drug resistance in NSCLC. The potential applications for this finding are provided evidence to screen the potential P-gp reversors and to diagnose and manage the chemoresistance in NSCLC patients. PMID- 22782457 TI - Diagnostic accuracy of CT readings on coin lesions in the lung as compared with transthoracic CT-guided needle biopsy results. AB - BACKGROUND: The aim of this study was to compare chest CT film reading results with histopathological results after CT-guided transthoracic needle biopsy of the lung. In addition, lung lesion morphology was evaluated and compared with the nature of the lesions. PATIENTS AND METHODS: Pulmonary lesions of 133 patients who underwent chest CT were retrospectively grouped into benign, malignant or uncertain. All patients underwent CT-guided transthoracic biopsy. Results of CT diagnosis and histopathological evaluation were compared. In addition, CT features such as size, borders, shape and presence of necrosis were assessed and compared with histopathological results. RESULTS: In 129 patients adequate specimens were obtained. Comparison of CT diagnosis with the histopathological results yielded the following results for chest CT: sensitivity 95%, specificity 43%, positive predictive value 83%, and negative predictive value 75%. Lesions with spiculated margins turned out to be associated with a significantly higher number of malignant lesions than lesions with smooth or blurred margins (p < 0.05). Lesions size, lesion shape as well as the presence of necrosis showed no significant relation to nature of the lesions (p > 0.05). CONCLUSION: Radiological assessment of pulmonary lesions alone is not sufficient. the specificity of chest CT is not sufficient to make a definitive diagnosis, i. e., histological verification is still needed for further investigation in a large number of cases. Only lesions with spiculated margins showed a significantly higher number of malignant degenerations in histological evaluation. PMID- 22782458 TI - 4-aminopyridine toxicity: a case report and review of the literature. AB - INTRODUCTION: 4-Aminopyridine (4-AP) selectively blocks voltage-gated potassium channels, prolongs the action potential, increases calcium influx, and subsequently, enhances interneuronal and neuromuscular synaptic transmission. This medication has been studied and used in many disease processes hallmarked by poor neuronal transmission in both the central and peripheral nervous systems including: multiple sclerosis (MS), spinal cord injuries (SCI), botulism, Lambert Eaton syndrome, and myasthenia gravis. It has also been postulated as a potential treatment of verapamil toxicity and reversal agent for anesthesia-induced neuromuscular blockade. To date, there have been limited reports of either intentional or accidental 4-AP toxicity in humans. Both a case of a patient with 4-AP toxicity and review of the literature are discussed, highlighting commonalities observed in overdose. CASE REPORT: A 37-year-old man with progressive MS presented with diaphoresis, delirium, agitation, and choreathetoid movements after a presumed 4-AP overdose. 4-AP concentration at 6 h was 140 ng/mL. With aggressive benzodiazepine administration and intubation, he recovered uneventfully. DISCUSSION: The commonalities associated with 4-AP toxicity conforms to what is known about its mechanism of action combining cholinergic features including diaphoresis, altered mental status, and seizures with dopamine related movement abnormalities including tremor, choreoathetosis, and dystonia. Management of patients poisoned by 4-AP centers around good supportive care with definitive airway management and controlling CNS hyperexcitability aggressively with gamma-aminobutyric acid agonist agents. Adjunctive use of dopamine antagonists for extrapyramidal effects after sedation is a treatment possibility. As 4-aminopyridine recently received Federal Drug Administration approval for the treatment of ambulation in patients with MS, physicians should be keenly aware of its presentation, mechanism of action, and management in overdose. PMID- 22782459 TI - Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial. AB - RATIONAL: Autism is associated with activation of the inflammatory response system. OBJECTIVE: This study aims to assess the efficacy of a cyclooxygenase-2 inhibitor, celecoxib, as adjunctive therapy in the treatment of autism METHODS: In a 10-week randomized double-blind placebo-controlled study, 40 outpatient children with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision clinical diagnosis of autism were randomly allocated to celecoxib plus risperidone or placebo plus risperidone. The dose of risperidone and celecoxib were titrated up to 3 and 300 mg/day, respectively. Patients were assessed at baseline and after 2, 4, 6, and 10 weeks of starting medication using the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. Primary outcome measure was the change in irritability subscale of ABC-C. RESULTS: Significant time * treatment interaction was observed for Irritability (F (1.658, 63.021) = 13.580, P < 0.001), Lethargy/Social Withdrawal (F (1.948, 74.032) = 16.811, P < 0.001), and Stereotypic Behavior (F(1.742, 66.198) = 12.104, P < 0.001), but not for Hyperactivity/Noncompliance (F (2.564, 97.424) = 1.469, P = 0.232), and Inappropriate Speech subscales (F (1.607, 61.075) = 0.173, P = 0.794). By week 10, patients in the celecoxib group showed significantly greater improvement in the Irritability (P < 0.001), Lethargy/Social Withdrawal (P < 0.001), and Stereotypic Behavior (P < 0.00) but not in Hyperactivity/Noncompliance (P = 0.202) and Inappropriate Speech (P = 0.802) subscales than the placebo group. Complete response was achieved by four (20 %) patients in the placebo group and 11 (55 %) patients in the celecoxib group (chi (2) (1) = 5.227, P = 0.022). Frequency of side effects was similar between the two groups. CONCLUSIONS: Combination of risperidone and celecoxib was superior to risperidone alone in treating irritability, social withdrawal, and stereotypy of children with autism. (Registration, www.irct.ir ; IRCT138711091556N2). PMID- 22782460 TI - Differences in vulnerability to nicotine-induced kindling between female and male periadolescent rats. AB - RATIONALE: It has recently been reported that chronic nicotine administration at subconvulsive doses causes seizures, a phenomenon referred to as kindling. Evidence points to the involvement of oxidative stress in pharmacological and electrical kindling, sex is known to influence the brain's response to nicotine. OBJECTIVES: This study investigated the sex differences in vulnerability to nicotine-induced kindling and the involvement of oxidative stress in this phenomenon. METHODS: Male and female periadolescent Wistar rats received repeated injections of a subconvulsive dose of nicotine (hemisulfate salt; 2 mg/kg, i.p.) every weekday for up to 25 days. To better understand the influence of oxidative stress in nicotine kindling, the antioxidant vitamin E (200 and 400 mg/kg, p.o.) was administered prior to nicotine administration. The levels of gluthatione (GSH), superoxide dismutase (SOD) activity, and lipid peroxidation were determined in the hippocampus (HC), prefrontal cortex (PFC), and striatum. RESULTS: Female animals developed kindling more rapidly than male rats. In female rats, kindling was associated with decreases in antioxidant defenses, including GSH levels in the HC and striatum and SOD activity in the PFC and striatum, and increased lipid peroxidation in all brain areas studied. By contrast, male kindled animals presented only with a decrease in the GSH in the HC. Vitamin E prevented the occurrence of kindled seizures by 80 % and 75 % in male and female rats, respectively. CONCLUSION: These novel findings indicate that female periadolescent rats develop nicotine-kindled seizures earlier than their male counterparts. Differences in the oxidative balance may be involved in this mechanism. PMID- 22782462 TI - Platelets guide lymphocytes to vascular injury sites. PMID- 22782461 TI - Association of abnormal semantic processing with delusion-like ideation in frequent cannabis users: an electrophysiological study. AB - RATIONALE: Frequent cannabis use is a risk marker for schizophrenia and delusions, but the neurocognitive mechanisms of this relationship remain unclear. OBJECTIVES: We sought evidence that cannabis users have deficits in processing relationships between meaningful stimuli, similar to abnormalities reported in schizophrenia, and that these deficits are associated with delusion-like ideation. We used the N400 event-related brain potential (ERP) waveform as a neurophysiological probe of activation of concepts in semantic memory. We hypothesized that cannabis users would exhibit larger (more negative) than normal N400 amplitudes in response to stimuli meaningfully related to a preceding prime reflecting deficient activation of concepts related to the prime. We further hypothesized that the magnitude of this abnormality would correlate with severity of delusion-like ideation. METHODS: We recorded ERPs in 24 frequent cannabis users and 24 non-using comparison participants who viewed prime words followed by targets which were either words related or unrelated to the prime or pronounceable nonwords. The participants' task was to indicate whether the target was a word. Delusion-like ideation was measured via the Schizotypal Personality Questionnaire. RESULTS: Contrary to our hypothesis, cannabis users exhibited smaller than normal N400s to both related and unrelated targets. These abnormalities correlated with delusion-like ideation in cannabis users only. CONCLUSIONS: The results are consistent with a generalized abnormality of activation within semantic memory neural networks in cannabis users. Further research is needed to investigate whether such an abnormality plays a role in the development of delusion-like ideation in cannabis users. PMID- 22782463 TI - Efficacy and safety of capecitabine plus cisplatin in Japanese patients with advanced or metastatic gastric cancer: subset analyses of the AVAGAST study and the ToGA study. AB - BACKGROUND: Capecitabine plus cisplatin (XP) is recognized as one of the global standard first-line chemotherapy regimens for patients with metastatic gastric cancer (mGC). Recent multinational phase III trials in mGC have been conducted with XP as the control arm, although no data on XP in Japanese patients with mGC have been published to date. The AVAGAST (XP +/- bevacizumab in mGC) and ToGA (XP +/- trastuzumab in human epidermal growth factor receptor 2 [HER2]-positive mGC) studies were the first two global studies including Japanese mGC patients. The aim of this analysis was to investigate the efficacy and safety of XP in Japanese mGC patients, using AVAGAST and ToGA subgroup data. METHODS: Efficacy and safety analyses were carried out in Japanese patients with mGC receiving XP alone, based on results from the AVAGAST and ToGA studies. There were differences in the target populations between the two studies; for example, the ToGA study limited patients to those with HER2-positive tumors; therefore, efficacy was evaluated separately. RESULTS: Ninety-four Japanese patients in the AVAGAST study and 50 in the ToGA study received XP alone. Median overall and progression-free survivals were 14.2 and 5.7 months, respectively, in the AVAGAST study, and 17.7 and 5.6 months, respectively, in the ToGA study. Overall response rates were 49.2 % in the AVAGAST and 58.5 % in the ToGA study. Adverse events were generally mild; the most common grade 3/4 events were neutropenia, anemia, anorexia, and nausea. CONCLUSIONS: XP is effective and well tolerated in Japanese patients with mGC, and could be one of the standard regimens for the first-line treatment in this cohort. PMID- 22782465 TI - Response to Cole and Waldron's "letter to the editor: Syphilis revisited". PMID- 22782464 TI - Overweight is a risk factor for surgical site infection following distal gastrectomy for gastric cancer. AB - BACKGROUND: Our objective was to assess the risk factors for surgical site infections (SSIs) in gastric surgery using the results of the Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG) 0501 phase 3 trial. METHODS: The OGSG 0501 trial was conducted to compare standard prophylactic antibiotic administration versus extended prophylactic antibiotic administration in 355 patients who underwent open distal gastrectomy for gastric cancer. Various risk factors associated with the incidence of SSI following gastrectomy were analyzed from the results of this multi-institutional randomized controlled trial. RESULTS: Among the 355 patients, there were 24 SSIs, for an overall SSI rate of 7 %. Multivariate analysis using eight baseline factors (administration of antibiotics, age, sex, body mass index [BMI], prognostic nutritional index, tumor stage, lymph node dissection, reconstructive method) identified that BMI >= 25 kg/m(2) was an independent risk factor for the occurrence of SSI (odds ratio 2.82; 95 % confidence interval [CI] 1.05-7.52; P = 0.049). BMI also showed significant relationships with the volume of blood loss and the operation time (P = 0.001 and P < 0.001, respectively). CONCLUSION: Compared with patients of normal weight, overweight patients had a significantly higher risk of SSI after distal gastrectomy for cancer. PMID- 22782467 TI - Detection of virulence factors and molecular typing of pathogenic Leptospira from capybara (Hydrochaeris hydrochaeris). AB - Leptospirosis is a globally prevalent zoonosis caused by pathogenic Leptospira spp.; several serologic variants have reservoirs in synanthropic rodents. The capybara is the largest living rodent in the world, and it has a wide geographical distribution in Central and South America. This rodent is a significant source of Leptospira since the agent is shed via urine into the environment and is a potential public health threat. In this study, we isolated and identified by molecular techniques a pathogenic Leptospira from capybara in southern Brazil. The isolated strain was characterized by partial rpoB gene sequencing and variable-number tandem-repeats analysis as L. interrogans, serogroup Icterohaemorrhagiae. In addition, to confirm the expression of virulence factors, the bacterial immunoglobulin-like proteins A and B expression was detected by indirect immunofluorescence using leptospiral specific monoclonal antibodies. This report identifies capybaras as an important source of infection and provides insight into the epidemiology of leptospirosis. PMID- 22782466 TI - Association between cardiovascular disease risk factors and occurrence of venous thromboembolism. A time-dependent analysis. AB - Apart from obesity, it remains controversial whether atherosclerosis and its cardiovascular risk disease (CVD) factors are associated with risk of venous thromboembolism (VTE). Using data from the Atherosclerosis Risk in Communities study (ARIC), we evaluated associations between CVD risk factors and incident VTE in a cohort of 15,340 participants who were free a history of VTE and/or anticoagulant use on enrolment. The CVD risk factors were updated during the follow-up period. Over a mean follow-up time of 15.5 years (237,375 person years), 468 participants had VTE events. Adjusting for demographic variables and body mass index (BMI), current smokers were at greater risk [HR of 1.44 (95% CI: 1.12-1.86)] compared to non-smokers. There was a positive monotonic association between BMI and VTE risk. Individuals with a BMI >=35 kg/m2 had a HR for VTE of 3.09 (95%CI: 2.26-4.23) compared to those with normal BMI (<25 kg/m2). Greater physical activity was associated with lower VTE risk in a demographic adjusted model; however, this association became non-significant following adjustment for BMI. Alcohol intake, diabetes, hypertension, high-density lipoprotein and low density lipoprotein cholesterol, and triglycerides were not associated with VTE risk. In conclusion, among the well-established CVD risk factors, only current smoking and obesity were independently associated with VTE risk in this large cohort where risk factors were updated serially during follow-up. This finding corroborates that the pathogenesis of venous disease differs from that of atherosclerotic disease. PMID- 22782468 TI - Soybean seed lectin prevents the accumulation of S-adenosyl methionine synthetase and the S1 30S ribosomal protein in Bradyrhizobium japonicum under C and N starvation. AB - Soybean lectin (SBL) participates in the recognition between Bradyrhizobium japonicum and soybean although its role remains unknown. To search for changes in the proteome in response to SBL, B. japonicum USDA 110 was incubated for 12 h in a C- and N-free medium with or without SBL (10 MUg ml(-1)), and the soluble protein profiles were compared. Two polypeptides, S-adenosyl-methionine synthetase (MetK) and the 30S ribosomal protein S1 (RpsA), were found only in the fractions from rhizobia incubated without SBL. Transcript levels of metK and rpsA were not correlated with polypeptide levels, indicating that there was regulation at translation. In support of this proposal, the 5' translation initiation-region of rpsA mRNA contained folding elements as those involved in regulation of its translation in other species. Disappearance of MetK and RpsA from the soluble protein fractions of SBL-treated rhizobia suggests that SBL might have attenuated the nutritional stress response of B. japonicum. PMID- 22782470 TI - Profiling surface glycans on live cells and tissues using quantum dot-lectin nanoconjugates. AB - The surface of mammalian cells is densely coated with complex glycans, which are directly involved in cell-cell or cell-protein interactions that trigger various biological responses. Here, we present a novel glycomics approach that uses quantum dot (Qdot)-lectin nanoconjugates to interrogate the surface glycans of tissues and patterned cells. Our approach allows highly sensitive in situ monitoring of specific lectin-glycan interactions and quantitative information on surface glycans for each examined cell line and tissue. The results clearly show significant changes in glycosylation for each cell line and tissue sample. We expect that these results will be applicable in cancer diagnostics and promote the development of new analytical tools for glycomics. PMID- 22782469 TI - Quorum sensing inhibition in Pseudomonas aeruginosa PAO1 by antagonistic compound phenylacetic acid. AB - In Pseudomonas aeruginosa, quorum sensing (QS) autoinducer known as acyl homoserine lactone (AHL) acts as a key regulator in the expression of pathogenic characters. In this work, the efficiency of phenylacetic acid (PAA) in reducing the production of AHL-dependent factors in P. aeruginosa PAO1 was studied. PAA at a concentration of 200 MUg ml(-1) displayed significant reduction in QS-dependent pyocyanin, exopolysaccharide, and protease and elastase production in PAO1. In swimming inhibition assay, PAA-treated PAO1 cells exhibited poor motility in swimming agar plate. In in vivo analysis, PAO1-preinfected Caenorhabditis elegans showed enhanced survival when treated with PAA. PAA at the QS inhibitory concentration showed no growth inhibitory activity on PAO1. Results of the present study revealed the potential of PAA as antipathogenic compound to prevent QS-dependent pathogenicity of P. aeruginosa. PMID- 22782471 TI - In vitro human cell-free expression system for synthesis of malaria proteins. AB - In this study, we performed cell-free expression of Plasmodium proteins using the in vitro human cell-free protein expression systems for DNA and mRNA. Malaria rhoptry genes (PFc14_0344, PFc0120w, PY01759, PY00763, PY07482, and PY04666) and a Maurer's cleft gene (PfA0680c) identified from proteome analysis studies were cloned into the pT7CFE1-CHis expression vector. Following a coupled transcription translation procedure, expressed proteins were analyzed by His-tag staining and by western blotting using protein specific antibodies and nickel-horseradish peroxidase (HRP) for histidine detection. Antibodies against whole rhoptries of Plasmodium falciparum and Plasmodium yoelii merozoites and antibodies specific for the PfMC-2TM protein identified translated proteins. The rhoptry specific antibodies exhibited cross reactivity among the expressed proteins of P. falciparum and P. yoelii. The results demonstrate that the in vitro human cell free protein expression system is suitable for rapid expression and screening of malaria vaccine candidates and diagnostic biomarkers. PMID- 22782472 TI - Nomuraea rileyi as biological control agents of Rhipicephalus microplus tick. AB - Nomuraea rileyi, a fungus pathogenic to insects, has been widely used for biological control of agricultural pests in Brazil. This study investigates the effects of N. rileyi, isolates Nr 138, Nr 151, and Nr 177, to eggs, larvae, and engorged females of Rhipicephalus microplus tick. Specimens were immersed in 1 ml of conidial suspension for 3 min, whereas the control group was immersed in 0.01% Tween 80 water solution. The isolate Nr 138 controlled 67.37% of ticks when the highest conidial concentration was used, 10(8) conidia ml(-1). The isolate Nr 177 significantly reduced the percentage of hatch of larvae from eggs treated with 10(8) conidia ml(-1). Conversely, the isolate Nr 151 was not virulent to eggs, larvae, or adults. Variability in virulence was observed among the N. rileyi isolates investigated in the current study-Nr 138 was more virulent to engorged females, while Nr 177 was more virulent to unfed larvae. Although N. rileyi proved to be virulent to several stages of R. microplus, the results obtained in this study indicate that N. rileyi does not appear to be a remarkable biological control agent for R. microplus. PMID- 22782473 TI - Myxozoan infection of the Malaysian mahseer, Tor tambroides, of Tasik Kenyir Reservoir, Malaysia: description of a new species Myxobolus tambroides sp.n. AB - Tor tambroides, a common and appreciated cyprinid fish of the Tasik Kenyir water reservoir in Malaysia, is one of the species selected for propagation. This fish was first successfully propagated in Malaysia by the Department of Agriculture, Sarawak, Malaysia, and the breeding program continued throughout the country. The gills were frequently infected by a Myxobolus species to be described as Myxobolus tambroides sp. n. The small, 50 to 70 MUm, round plasmodia of this species is located intralamellarly. Plasmodia were filled with pyriform myxospores, 9.9 and 7.4 MUm wide. In sutural view, the caudal end of the myxospores had a distinctive valvular groove, parallel with the suture. Plasmodia caused deformations on the affected and the neighbouring gill lamellae. The 18S rDNA sequence of M. tambroides sp.n. did not show a close relationship with any other Myxobolus spp., represented in the GenBank. This might be an emerging parasite likely to impact the propagation of this fish. PMID- 22782474 TI - Susceptibility of different life stages of Ornithodoros lahorensis to entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana. AB - The use of chemicals for the control of arthropod pests can be problematic due to the potential for both environmental contamination and resistance development. As a result, there is an increasing interest in nonchemical alternatives, such as biocontrol by entomopathogenic fungi. In the present study, three strains of Metarhizium anisopliae (V245, 3247, and 4456) and one strain of Beauveria bassiana (LM 3.2) were evaluated under laboratory conditions for their virulence towards three life stages of Ornithodoros lahorensis. Groups of eggs, larvae, and adult ticks were treated by immersion in two different suspensions (10(5) and 10(7) conidia/ml) of each fungal strain. All treatment and control groups were observed during a 3-week period, and the hatchability of eggs and mortality percentage of larvae and adult ticks were assessed. The effect of fungal strains on egg hatchability and larva and adult mortality was significant and dose dependent compared to the control groups (P < 0.05). The results also showed that the greatest biopesticidal effect was due to strain 4456 of M. anisopliae and LM 3.2 strain of B. bassiana at all tested concentrations, making these fungi potential biological control agents of O. lahorensis reducing the use of chemical acaricides. PMID- 22782475 TI - Identification and characterization of a Chinese isolate of Cryptosporidium serpentis from dairy cattle. AB - Cryptosporidium serpentis, a protozoan observed first in snakes, has also been found in lizards and other reptiles. However, there are few reports of the characteristics of C. serpentis isolated from humans and other animals. The present study was undertaken to characterize a C. serpentis isolate from a calf in terms of morphology, host specificity, and small-subunit ribosomal RNA (SSU rRNA) and heat shock protein 70 (HSP 70) gene sequences. Oocysts of the isolate measured 6.32 * 5.18 MUm, and they had a length/width shape index of 1.22. A cross-transmission study demonstrated that the isolate was infectious in the stomach of BALB/c mice, but not in New Zealand white rabbits or white leghorn chickens. Sequence and phylogenetic analysis of the SSU rRNA and HSP 70 gene revealed that the isolate was identical to C. serpentis, and it was classified in a monophyletic group of C. serpentis. This study is the first description of the characteristics of a C. serpentis isolate from dairy cattle and may contribute to a better understanding of C. serpentis and investigations of the prevalence of Cryptosporidium in cattle. PMID- 22782476 TI - Efficacy and safety of imidacloprid 10%/moxidectin 1% spot-on formulation in the treatment of feline infection by Capillaria aerophila. AB - The nematode Capillaria aerophila (Trichuroidea, Trichuridae) affects the respiratory system of cats and other animals and occasionally of human beings. Infected cats may show bronchovesicular sounds, inflammation, sneezing, wheezing and, chronic cough and, sometimes, bronchopneumonia and respiratory failure. The present study evaluated the efficacy and safety of the antiparasitic spot-on formulation containing imidacloprid 10%/moxidectin 1 % (Advocate(r), Bayer Animal Health) in the treatment of natural feline infection with the lungworm C. aerophila. The efficacy of Advocate(r) administered once was tested on days 7 +/- 1 and 11 +/- 1 following treatment at day 0 and compared to faecal egg counts on days -6 +/- 1 and -2 +/- 1. Overall, 36 cats treated either with Advocate(r) (treatment group, n = 17 cats) or left untreated (control group, n = 19 cats) were included in the study. Geometric means of faecal egg counts values in eggs per gram of faeces were 124.03 prior to treatment and 0.26 posttreatment in treatment group, while 107.03 and 123.94 pre- and posttreatment in the untreated cats. Post-baseline egg counts showed a 99.79 % reduction in Advocate(r)-treated animals in comparison with cats which were left untreated. Also, treated cats showed no adverse events. This trial demonstrated that Advocate(r) spot-on formulation is safe and effective in the treatment of feline lung capillariosis caused by C. aerophila. PMID- 22782477 TI - Identification and frequency distribution of Leishmania (L.) major infections in sand flies from a new endemic ZCL focus in southeast Iran. AB - Zoonotic cutaneous leishmaniasis (ZCL) is an important public health challenge in Iran. It is often caused by the protozoan parasite, Leishmania major. This pathogen is principally transmitted by the infectious bites of adult female phlebotomine sand flies which belong to the subgenus Phlebotomus (Phlebotomus) Rondani and Berte (Diptera: Psychodidae). A recent outbreak of clinical ZCL cases in the rural district of Jask, Hormozgan province, southern Iran prompted the identification of sand flies naturally infected with L. major using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). A total of 8,123 wild sand flies were caught using sticky paper traps indoors and outdoors in seven villages of Jask from March 2007 to February 2008. About 120 trap-nights per month were carried out during peak seasonal density. Eight sand fly species of two distinct genera were morphologically identified. The most abundant species, Phlebotomus papatasi (~60%) and Phlebotomus salehi (17%), had simultaneous population peaks in May and October. The anthropophilic index of P. papatasi was approximately twice that of P. salehi. PCR reactivity of L. major infections in P. salehi was weaker than those in P. papatasi. This is discussed with regard to their role in the natural transmission cycle of ZCL. This study provided the first PCR and ELISA evidence on P. salehi as a vector of L. major parasites in a new endemic region of ZCL in southeast Iran. PMID- 22782478 TI - Effects of the Chinese medicine matrine on experimental C. parvum infection in BALB/c mice and MDBK cells. AB - To date, there are no effective methods of treating Cryptosporidium infection in animals or humans. Matrine, a main active alkaloid extract from Sophora flavescens, has potential antineoplastic, antifibrotic, anti-inflammatory, and antitumor activities. However, the treating effects of matrine on Cryptosporidium infection as well as its mechanisms of action are largely unknown. The present study investigated the effects of matrine on Cryptosporidium parvum infection in both in vitro and in vivo models. Oocyst excretion, plasma D-lactic acid concentrations, and bacterial translocation rates were assayed to evaluate the efficacy of treatment in experimentally infected BALB/c mice. Matrine effects on parasite replication and lactate dehydrogenase (LDH) activity were assessed in cell cultures. The results showed that matrine could significantly reduce the number of C. parvum oocysts by 54-63%, and the number of C. parvum-infected cells by 28-58%. Plasma D-lactic acid concentrations and LDH activity in the matrine treated groups were lower than the infected group (P < 0.05) and higher than the control (P < 0.05). The bacterial translocation rates in groups treated with matrine at high doses were lower than the infected group (P < 0.05) and not higher than the control (P > 0.05). These results clearly demonstrate that matrine can inhibit C. parvum infection. Integrity of cell membranes and of the mucosal barrier is improved in treated animals as compared to untreated infected controls. Thus, it is concluded that matrine has a potential in therapeutic applications against C. parvum infection. PMID- 22782479 TI - Z-BN: a novel superhard boron nitride phase. AB - A superhard boron nitride phase dubbed as Z-BN is proposed as a possible intermediate phase between h-BN and zinc blende BN (c-BN), and investigated using first-principles calculations within the framework of density functional theory. Although the structure of Z-BN is similar to that of bct-BN containing four-eight BN rings, it is more energetically favorable than bct-BN. Our study reveals that Z-BN, with a considerable structural stability and high density comparable to c BN, is a transparent insulator with an indirect band gap of about 5.27 eV. Amazingly, its Vickers hardness is 55.88 GPa which is comparable to that of c-BN. This new BN phase may be produced in experiments through cold compressing AB stacking h-BN due to its low transition pressure point of 3.3 GPa. PMID- 22782480 TI - Oral hapsis guides accurate hand preshaping for grasping food targets in the mouth. AB - Preshaping the digits and orienting the hand when reaching to grasp a distal target is proposed to be optimal when guided by vision. A reach-to-grasp movement to an object in one's own mouth is a natural and commonly used movement, but there has been no previous description of how it is performed. The movement requires accuracy but likely depends upon haptic rather than visual guidance, leading to the question of whether the kinematics of this movement are similar to those with vision or whether the movement depends upon an alternate strategy. The present study used frame-by-frame video analysis and linear kinematics to analyze hand movements as participants reached for ethologically relevant food targets placed either at a distal location or in the mouth. When reaching for small and medium-sized food items (blueberries and donut balls) that had maximal lip-to target contact, hand preshaping was equivalent to that used for visually guided reaching. When reaching for a large food item (orange slice) that extended beyond the edges of the mouth, hand preshaping was suboptimal compared to vision. Nevertheless, hapsis from the reaching hand was used to reshape and reorient the hand after first contact with the large target. The equally precise guidance of hand preshaping under oral hapsis is discussed in relation to the idea that hand preshaping, and its requisite neural circuitry, may have originated under somatosensory control, with secondary access by vision. PMID- 22782481 TI - Alpha oscillations and the control of voluntary saccadic behavior. AB - The purpose of this review is to explore the dynamic properties of alpha oscillations as biological covariates of intra- and inter-individual variance in saccadic behavior. A preponderance of research suggests that oscillatory dynamics in the alpha band co-vary with performance on a number of visuo-spatial cognitive tasks. Here we discuss a growing body of research relating these measures to saccadic behavior, focusing also on how task related and spontaneous measures of alpha oscillations may serve as potential biomarkers for ocular motor dysfunction in clinical populations. PMID- 22782482 TI - Parietal double-cone coil stimulation in tinnitus. AB - Non-pulsatile tinnitus is considered to be an auditory phantom percept. The extremely emotional context of disabling tinnitus often leads to a higher level of selective attention directed toward the tinnitus. As such, tinnitus is a continuously distracting auditory event. Auditory attention is associated with the activation of the intraparietal sulcus (IPS), and modulating the IPS with 10 Hz transcranial magnetic stimulation (TMS) creates the ability to ignore salient distractors. Thus, it can be expected that modulating the parietal area might interfere with the perception of tinnitus. The effect of TMS on tinnitus is evaluated using a double-cone coil tilted to the left parietal area in 24 individuals (study 1) and in 40 individuals with the double-cone coil symmetrically overlying both parietal areas (study 2). When transient tinnitus suppression is noted, the patient is asked to estimate the decrease in tinnitus in percentage using the numeric rating scale. The procedure is repeated with stimulations at sham, 1 and 10 Hz, each stimulation session consisting of 200 pulses for study 1 and for study 2 stimulations at sham, 1, 5, and 10 Hz, each stimulation session consisting of 200 pulses. For both studies, the order of the different stimulation frequencies was randomized over the participants. For study 1, patients report a significant transient reduction of the tinnitus percept for 10 Hz stimulation in comparison with, respectively, pre-treatment, sham, and 1 Hz stimulation, with a suppression effect of 11.36 %. No significant effect was obtained for 1 Hz stimulation with the coil tilted toward the left parietal area. For study, 2 patients revealed a significant suppression effect on 1, 5, and 10 Hz in comparison with pre-treatment. However, only stimulation at 5 and 10 Hz had a significant difference in comparison with sham with a suppression effect of, respectively, 8.78 and 9.50 %. Our data suggest that the parietal area is involved in tinnitus perception and that 10 Hz TMS using the double-cone coil overlying the parietal area can modulate tinnitus. PMID- 22782483 TI - The involvement of the left ventrolateral prefrontal cortex in tinnitus: a TMS study. AB - Tinnitus is an auditory phantom percept with a tone, hissing or buzzing sound in the absence of any objective physical sound source. Tinnitus is considered to be an auditory phantom phenomenon analogous to somatosensory phantom pain. Controllable versus uncontrollable pain is characterized by an increased activity in the ventrolateral prefrontal cortex (VLPFC), and activation in the VLPFC correlating with perceived control over pain results in a decrease in subjective pain intensity. Depressed individuals show less activation than healthy controls in the left VLPFC in response to sad autobiographical scripts, and greater relative left prefrontal activation is related to a greater disposition to approach-related, positive affect with a greater ability to regulate negative affect. Based on the theory that non-pulsatile tinnitus can be considered the auditory analogue for deafferentation pain, we hypothesize that the left VLPFC might also be involved in control of tinnitus. We conducted a transcranial magnetic stimulation (TMS) study verifying whether modulating the left VLPFC by TMS can modulate the loudness of tinnitus. We studied 60 patients with chronic tinnitus of which 21 patients received in random order sham and 1-Hz stimulation, while 39 patients received in random order sham and 10-Hz stimulation. Our results show that 10-Hz stimulation can modulate tinnitus loudness, while 1-Hz stimulation does not seem to exert the same effect. Our findings give further support to the fact that non-auditory areas are involved in tinnitus. PMID- 22782484 TI - Meeting report: The second Tianjin Forum on tumor microenvironment, Tianjin, China, June 22-24, 2012. PMID- 22782485 TI - Multicenter phase II study of second-line bevacizumab plus doublet combination chemotherapy in patients with metastatic colorectal cancer progressed after upfront bevacizumab plus doublet combination chemotherapy. AB - BACKGROUND: To investigate the efficacy and safety of bevacizumab beyond first progression combined with doublet chemotherapy in patients with metastatic colorectal cancer. METHODS: This multicenter phase II study included 76 patients with metastatic colorectal cancer progressed after first-line bevacizumab plus doublet chemotherapy. Study treatment consisted of second-line continuation of bevacizumab plus crossover standard doublet chemotherapy, consisting of FOLFOX, CapeOX, or FOLFIRI. Bevacizumab was administered in doses of 5 mg/kg/2-week or 7.5 mg/kg/3-week according to the schedules of the combined regimen. RESULTS: Median progression-free survival (PFS) and overall survival (OS) was 6.5 months (95 % CI, 5.2-7.8) and 12.8 months (95 % CI, 8.8-16.9), respectively, with no significant differences according to combined doublet chemotherapy. The response rate (RR) was 17.1 % (95 % CI, 8.6-5.6) with no statistical significance between regimens (p = 0.053). The first-line RR and PFS did not affect the second-line efficacy outcomes; RR (14.0 % vs 21.2 %, p = 0.405), median PFS (5.6 vs 6.7 months, p = 0.335), and OS (15.4 vs 11.0 months, p = 0.383) were not different between previous responders and non-responders, and the median PFS (p = 0.186) and OS (p = 0.495) were not different either according to the length of first line PFS; however, OS from the first-line chemotherapy was longer in patients with longer first-line PFS (26.4 vs 14.8 months, p = 0.010). Bevacizumab-related significant adverse events included proteinuria (1.3 %) and thromboembolism (1.3 %). CONCLUSIONS: Bevacizumab beyond first progression could be considered a treatment strategy even in patients progressed after first-line bevacizumab plus doublet chemotherapy. Second-line efficacy outcomes did not differ according to the first-line responses. PMID- 22782486 TI - Sequences of small blaTEM-encoding plasmids in Haemophilus influenzae and description of variants falsely negative for blaTEM by PCR. AB - OBJECTIVES: To characterize an unidentified beta-lactamase and associated genetic background in a bla(TEM) and bla(ROB) PCR-negative Haemophilus influenzae isolate, and characterize small bla(TEM)-encoding plasmids in a collection of H. influenzae. METHODS: The unidentified beta-lactamase gene was identified by cloning and sequencing the encoding plasmid. Strains with small bla(TEM) plasmids were identified using negative PCR for integrative conjugative elements, but positive bla(TEM) PCR; plasmids from selected isolates were sequenced. PCR for rep and divergent bla(TEM) were evaluated for detecting small plasmids on selected H. influenzae isolates. RESULTS: Small plasmids (4.8-5.5 kb) encoding bla(TEM) appear to be associated with remnants of Tn2 on a conserved plasmid core. The unidentified beta-lactamase was actually a TEM-1, with negative bla(TEM) PCR associated with a previously unrecognized deletion of bp 1-27 of bla(TEM) (Sutcliffe numbering) associated with a larger deletion within Tn2. This deletion was found in other isolates and may be more common than previously thought. PCR for the conserved rep gene appears useful for screening for small bla(TEM)-encoding plasmids or associated cryptic plasmids in H. influenzae. CONCLUSIONS: Small bla(TEM)-encoding plasmids in H. influenzae appear relatively conserved, but require further study to confirm this. PCR associated with the rep gene may be useful for studying these small plasmids. A deletion in part of bla(TEM) in some strains may interfere with some PCRs; therefore, care should be taken with primer selection or design and, preferably, regions within the open reading frame should be targeted. PMID- 22782487 TI - Identification of acquired antimicrobial resistance genes. AB - OBJECTIVES: Identification of antimicrobial resistance genes is important for understanding the underlying mechanisms and the epidemiology of antimicrobial resistance. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available in routine diagnostic laboratories and is anticipated to substitute traditional methods for resistance gene identification. Thus, the current challenge is to extract the relevant information from the large amount of generated data. METHODS: We developed a web-based method, ResFinder that uses BLAST for identification of acquired antimicrobial resistance genes in whole-genome data. As input, the method can use both pre-assembled, complete or partial genomes, and short sequence reads from four different sequencing platforms. The method was evaluated on 1862 GenBank files containing 1411 different resistance genes, as well as on 23 de-novo-sequenced isolates. RESULTS: When testing the 1862 GenBank files, the method identified the resistance genes with an ID = 100% (100% identity) to the genes in ResFinder. Agreement between in silico predictions and phenotypic testing was found when the method was further tested on 23 isolates of five different bacterial species, with available phenotypes. Furthermore, ResFinder was evaluated on WGS chromosomes and plasmids of 30 isolates. Seven of these isolates were annotated to have antimicrobial resistance, and in all cases, annotations were compatible with the ResFinder results. CONCLUSIONS: A web server providing a convenient way of identifying acquired antimicrobial resistance genes in completely sequenced isolates was created. ResFinder can be accessed at www.genomicepidemiology.org. ResFinder will continuously be updated as new resistance genes are identified. PMID- 22782488 TI - Efficacy and tolerability of oleylphosphocholine (OlPC) in a laboratory model of visceral leishmaniasis. AB - OBJECTIVES: The alkylphospholipid oleylphosphocholine (OlPC) is a structural analogue of miltefosine and may represent a potential therapeutic backup for the treatment of visceral leishmaniasis (VL). This laboratory study compared the in vitro and in vivo activity profile of both OlPC and miltefosine. METHODS: The in vitro potency of OlPC was compared with that of miltefosine, amphotericin B, paromomycin and pentavalent antimony (Sb(V)) using the intracellular amastigote assay on different Old World and New World Leishmania species. The in vivo efficacy was dose titrated in the Leishmania infantum hamster model after infection with 2 * 10(7) amastigotes (day 0) and oral treatment at day 21 using an aqueous (OlPC/H(2)O) and liposomal formulation of OlPC in single and repeated (5 day) oral dosing regimens. The amastigote reductions in the liver, spleen and bone marrow were assessed (day 35). RESULTS: The in vitro activity of OlPC against Leishmania donovani, L. infantum, Leishmania tropica, Leishmania mexicana and Leishmania panamensis showed mean IC(50) values <5 MUM, while the IC(50) values for Leishmania major and Leishmania braziliensis were 7.7 and 13.5 MUM, respectively. These results are fairly similar to those obtained for miltefosine. In the hamster model, treatment with 20 and 40 mg/kg for 5 days proved that both OlPC formulations were equipotent and showed a markedly higher efficacy compared with miltefosine. A single dosing of 100 mg/kg of OlPC/H(2)O or OlPC liposomes reduced the parasite burdens by 96.2% and 99.3% in liver, 99.8% and 99.9% in spleen, and 87.6% and 96.9% in bone marrow, respectively. No signs of toxicity or adverse drug-related effects were noted. CONCLUSIONS: These data suggest that OlPC may become a promising candidate to improve and simplify current case management of VL. Additional pharmacological and pharmacokinetic studies are ongoing to assess the full potential of OlPC as a 'drug candidate'. PMID- 22782489 TI - Emergence of resistance to fosfomycin used as adjunct therapy in KPC Klebsiella pneumoniae bacteraemia: report of three cases. PMID- 22782490 TI - Wheezing in infants: frequency, clinical characteristics and treatment. AB - OBJECTIVE: To estimate the frequency and describe the clinical characteristics and respective treatments of previous history of wheezing. METHODS: Infants aged 6-23 months with upper respiratory tract complaints and reporting previous wheezing were followed-up retrospectively. Data were registered on a validated standardized form. RESULTS: Out of 451 infants, 164 (36.4%; 95%CI:31.9-41.0) had a report of prior history of wheezing, 148 (32.8%; 95%CI:28.5-37.4) during the first year of life. The mean age at the first episode of wheezing was 5.3+/-3.9 months. Among those who had had their first episode before 12 months of age, 38.5% reported 3 to 6 episodes and 14.2% > 6 episodes. Mean age at first episode was lower for those with >= 3 episodes in comparison with those with <= 2 episodes (3.2+/-2.7 vs. 5.7+/-2.5 months, p < 0.001). CONCLUSION: One third of the infants reported wheezing during the first year of life. The earlier the first episode occurs, the more frequently wheezing recurs. PMID- 22782491 TI - Optimum coupling and multimode excitation of traveling-waves in a whole-body 9.4T scanner. AB - Given the absence of a body coil, the radio frequency screen of a whole-body 9.4T magnetic resonance imaging scanner can be used as a circular waveguide. In the unloaded case, the screen allows propagation of the dominant TE11- as well as the TM01-mode. In the first part of this study, the optimum coupling of a circular polarized TE11-mode was determined empirically for excitation and reception with a rectangular patch antenna. Employing full-wave simulations, two simulation models and two phantoms, different patch positions were tested to find the optimum position with respect to coupled power and homogenous excitation field. The best simulation results were validated with measurements. The second part of this study describes the design and measurements of a multimode excitation device. Using the parallel transmit system of the MR scanner, all propagable traveling wave modes could be excited and detected independently. The performance of the multimode device related to field of view, B1+-efficiency and radio frequency shimming was assessed by phantom measurements. Initial results show that three modes are sufficient to homogeneously excite regions of interest at 9.4 T. PMID- 22782492 TI - A technical approach for transfemoral managing of hostile angulated pelvic vessel access in abdominal endovascular aneurysm repair: a new technique for establishing a buddy wire. AB - PURPOSE: Endovascular aneurysm repair (EVAR) can be challenging in angulated access vessels. The aim of this study was to evaluate a new wire technique for installing a buddy wire in the event of failure of simple advancing of a super stiff guide. MATERIALS AND METHOD: We investigated 8 patients eligible for EVAR. All patients presented with heavily kinked pelvic access and failure of primary advancing of a stiff guide wire through a placed catheter. A double wire technique with a combination of soft and stiff wires was applied to place a super stiff buddy wire. Cumulative angulation quantified by the sum of angles of the tortuous pelvic access vessels was measured in pre- and post-interventional CT as well as in angiographic studies of the EVAR procedure. Patients were followed up on by CT in the first 6 months. RESULTS: A buddy wire could be installed in all patients (100%) with significant straightening of the access vessel from a median cumulative angulation of 252.4+/-38.1 degrees before intervention to 159.4+/ 44.6 degrees after placement of the buddy wire (p<0.001). There was no technical failure of device passage and all stent-grafts could be deployed safely. Three cases of stenosis caused by torsion distal to the aortic stent-graft were seen after stent-graft delivery. One case of stenosis was hemodynamically relevant and was successfully stented. No major adverse events occurred within the first 6 months of follow-up. CONCLUSION: The new step-by-step wire technique is feasible and safe in the case of hostile pelvic vessel access, and facilitates the advancement of aortic stent-grafts in off-label patients. PMID- 22782493 TI - Association between preterm delivery and pre-pregnancy body mass (BMI), exercise and sleep during pregnancy among working women in Southern California. AB - Little is known about modifiable lifestyle factors beyond quitting smoking that could prevent preterm delivery (PTD, <37 weeks gestation). We examined the individual and joint associations of pre-pregnancy BMI, second trimester exercise and sleep on PTD. We conducted a nested, population-based case-control study interviewing postpartum 344 cases delivering at <37 weeks, as identified by clinical estimate of gestational age from prenatal screening records, and 698 term controls, excluding term low birthweight. Eligible women participated in California's statewide Prenatal Screening Program, worked during pregnancy, and delivered a singleton birth in Southern California in 2002-2003. Modeled separately, moderate (odds ratio [OR] = 0.90; 95% confidence interval [CI] = 0.84 0.96--per hour/week) and vigorous (OR = 0.67; 95% CI = 0.46-0.98 for yes vs. no) exercise during the second trimester were associated with a reduced odds of PTD, and sleep duration was not (OR = 1.09, 95% CI = 0.80-1.48 for <7 h; OR = 0.88, 95% CI = 0.57-1.48 for >8 h vs. 7-8 h). When sleep and exercise variables were modeled together along with pre-pregnancy BMI, only moderate exercise (OR = 0.91; 95% CI 0.85-0.98) continued to be associated with reduced odds of PTD. The benefits of moderate exercise appeared strongest for women with BMI greater than 24 kg/m(2) (OR = 0.85; 95% CI = 0.79-0.93) and weakened with decreasing BMI. No other interactions were found. Moderate exercise is associated with reduced PTD, particularly for women with BMI above the normal range. The results are of public health relevance given that these risk factors are potentially modifiable both pre-conceptionally and during pregnancy and rates of PTD are still high in the United States. PMID- 22782494 TI - Crania with mutilated facial skeletons: a new ritual treatment in an early pre pottery Neolithic B cranial cache at Tell Qarassa North (South Syria). AB - The removal of crania from burials, their ritual use and their disposal, generally in cranial caches, are the most particular characteristics of the funerary ritual in the transition to the Neolithic in the Near East. Despite the importance of this ritual, detailed studies of cranial caches are rare. This funerary ritual has traditionally been interpreted as a form of ancestor veneration. However, this study of the cranial caches found at the site of Tell Qarassa North, South Syria, dated in the second half of the ninth millennium BC, questions this interpretation. The 12 crania, found in two groups arranged in two circles on the floor of a room, belonged to male individuals, apart from one child and one preadolescent. In 10 of the 11 cases, the facial skeletons were deliberately mutilated. In the context of the Pre-Pottery Neolithic B, when the symbolism of the human face played a vital role in ritual practice, this mutilation of the facial skeleton could be interpreted as an act of hostility. In the absence of indicators of social stratification or signs of violence that might indicate more coercive forms of society, the veneration of ancestors has been explained as a mechanism for social cohesion, which would have been necessary in a context of rapid growth in the population of settlements. However, data on the negative nature of some funerary rites, of punishment or indifference rather than veneration, should make us question an over-idealized view of the first Neolithic societies. PMID- 22782496 TI - Effects of salinity on the immune response of an 'osmotic generalist' bird. AB - Salt stress can suppress the immune function of fish and other aquatic animals, but such an effect has not yet been examined in air-breathing vertebrates that frequently cope with waters (and prey) of contrasting salinities. We investigated the effects of seawater salinity on the strength and cost of mounting an immune response in the dunlin Calidris alpina, a long-distance migratory shorebird that shifts seasonally from freshwater environments during the breeding season to marine environments during migration and the winter period. Phytohaemagglutinin (PHA)-induced skin swelling, basal metabolic rate (BMR), body mass, fat stores, and plasma ions were measured in dunlins acclimated to either freshwater or seawater (salinity: 0.3 and 35.0 0/00, respectively). Seawater-acclimated dunlins mounted a PHA-induced swelling response that was up to 56 % weaker than those held under freshwater conditions, despite ad libitum access to food. Freshwater acclimated dunlins significantly increased their relative BMR 48 h after PHA injection, whereas seawater-acclimated dunlins did not. However, this differential immune and metabolic response between freshwater- and seawater acclimated dunlins was not associated with significant changes in body mass, fat stores or plasma ions. Our results indicate that the strength of the immune response of this small-sized migratory shorebird was negatively influenced by the salinity of marine habitats. Further, these findings suggest that the reduced immune response observed under saline conditions might not be caused by an energy or nutrient limitation, and raise questions about the role of osmoregulatory hormones in the modulation of the immune system. PMID- 22782495 TI - Understanding pancreas development for beta-cell repair and replacement therapies. AB - The lack or dysfunction of insulin-producing beta-cells is the cause of all forms of diabetes. In vitro generation of beta-cells from pluripotent stem cells for cell-replacement therapy or triggering endogenous mechanisms of beta-cell repair have great potential in the field of regenerative medicine. Both approaches rely on a thorough understanding of beta-cell development and homeostasis. Here, we briefly summarize the current knowledge of beta-cell differentiation during pancreas development in the mouse. Furthermore, we describe how this knowledge is translated to instruct differentiation of both mouse and human pluripotent stem cells towards the beta-cell lineage. Finally, we shortly summarize the current efforts to identify stem or progenitor cells in the adult pancreatic organ and to harness the endogenous regenerative potential. Understanding development and regeneration of beta-cells already led to identification of molecular targets for therapy and informed on pathomechanisms of diabetes. In the future this knowledge might [corrected] lead to beta-cell repair and replacement therapies. PMID- 22782497 TI - Detrimental influence on performance of high temperature incubation in a tropical reptile: is cooler better in the tropics? AB - Global temperatures have risen over the last century, and are forecast to continue rising. Ectotherms may be particularly sensitive to changes in thermal regimes, and tropical ectotherms are more likely than temperate species to be influenced by changes in environmental temperature, because they may have evolved narrow thermal tolerances. Keelback snakes (Tropidonophis mairii) are tropical, oviparous reptiles. To quantify the effects of temperature on the morphology and physiology of hatchling keelbacks, clutches laid by wild-caught females were split and incubated at three temperatures, reflecting the average minimum, overall average and average maximum temperatures recorded at our study site. Upon hatching, the performance of neonates was examined at all three incubation temperatures in a randomized order over consecutive days. Hatchlings from the 'hot' treatment had slower burst swim speeds and swam fewer laps than hatchlings from the cooler incubation temperatures in all three test temperatures, indicating a low thermal optimum for incubation of this tropical species. There were no significant interactions between test temperature and incubation temperature across performance variables, suggesting phenotypic differences caused by incubation temperature did not acclimate this species to post-hatching conditions. Thus, keelback embryos appear evolutionarily adapted to development at cooler temperatures (relative to what is available in their habitat). The considerable reduction in hatchling viability and performance associated with a 3.5 degrees C increase in incubation temperature, suggests climate change may have significant population-level effects on this species. However, the offspring of three mothers exposed to the hottest incubation temperature were apparently resilient to high temperature, suggesting that this species may respond to selection imposed by thermal regime. PMID- 22782498 TI - Successful endovascular management of brain aneurysms presenting with mass effect and cranial nerve palsy. AB - Aneurysms presented with mass effect are traditionally treated by surgical clipping to decompress their mass effect. The aim of this work is to discuss the efficiency of endovascular techniques in treating 47 patients with variable sizes of intracranial aneurysms presented with mass effect and/or cranial nerve palsy. There were 47 patients with 47 unruptured aneurysms. Group I includes 28 giant aneurysms; all are treated by parent vessel occlusion with or without intra aneurysmal occlusion depending on anatomical locations. Group II includes 19 small and large aneurysms; all are treated by selective endosaccular occlusion with coils. Clinical presentations were ocular cranial nerve dysfunction (82.9%), optic nerve or chiasmatic dysfunction (21.2%), brain stem compression (8.5%), embolic (6%), epistaksis (4%), proptosis (2%), and bleeding per ear (2%). Out of 47 patients, symptoms were resolved in 31 cases (66%), improved in 10 cases (21%), and unchanged in six cases (13%). Out of 28 giant aneurysms, symptoms were resolved in 19 (68%), improved in four (14%), and unchanged in five (18%). Only four (14%) patients out of the 19 giant aneurysms with complete symptoms resolution showed significant mass reduction in MRI. Out of 19 non-giant aneurysm cases treated by selective endovascular occlusion with coils, symptoms were resolved in 12 cases (63%), improved in six (32%), and unchanged in one (5%). No complications from the treatment were observed. The longer the duration of symptoms before endovascular treatment is, the longer the duration till improvement or resolution postoperative in both groups. Recovery of aneurysm induced mass effect occurs in most patients both after parent vessel occlusion and after selective coiling, and is comparable to results after surgical clipping. The improvement starts independent of aneurysmal shrinkage in postoperative MRI follow-ups. The arrest of pulsations and partial shrinkage within the aneurysms after endovascular treatment may be the logical reason behind neurological recovery. PMID- 22782500 TI - Coexistence of bronchiectasis and rheumatoid arthritis: revisited. AB - The presence of bronchiectasis (BR) in patients with rheumatoid arthritis (RA) has been recognized for many decades; nevertheless, little research has been undertaken in this area. It is important to recognize that BR coexistent with RA differs from the other types of BR. The purpose of this descriptive review was to delineate the epidemiology, etiology, risk factors, pulmonary function testing, imaging, prognosis and management of concomitant BR and RA. To inform our study we searched the PubMed, EMBASE, CINAHL, and MEDLINE databases, using combinations of the following key words: computed tomography, lung function tests, rheumatoid arthritis, bronchiectasis, biological agents, and interstitial lung disease. The number of published papers covering this topic is limited, but several relevant conclusions can be drawn. Patients with concomitant RA and BR have worse obstructive airways disease, increased susceptibility to recurrent pulmonary infections, faster lung function decline, and higher mortality, compared with subjects with either RA or BR alone. The use of disease-modifying anti-rheumatic drugs (both biological and non-biological) for RA in RA-BR patients imparts a further challenge in managing these patients. Although there are not any published guidelines on the management of coexisting RA-BR, we have attempted to provide such recommendations, based on the literature review and our experience. PMID- 22782499 TI - The urokinase receptor (CD87) represents a central mediator of growth factor induced endothelial cell migration. AB - Angiogenesis, the sprouting of blood vessels form pre-existing vasculature after injury or in neoplastic diseases, is initiated by growth factor-induced endothelial cell migration. Recently, the major angiogenic growth factor VEGF165 has become the target of therapeutic interventions. However, this approach has been clinically proven to be of limited efficacy, which might be due to the fact that tumour angiogenesis is not only induced by VEGF, but also by a variety of other growth factors. Thus, the identification of a common downstream mediator of growth-factor-induced endothelial cell migration is mandatory to effectively interfere with (tumour-) angiogenesis. We found that the urokinase-type plasminogen activator (uPA)-system, which affects proteolytic as well as adhesive capacities, represents an essential regulatory mechanism in growth factor-induced endothelial cell migration and invasion. This mechanism was not limited to VEGF165, but mediated pro-angiogenic endothelial cell behaviour induced by various growth factors. Thus, VEGF165, VEGF-E, FGF-2, EGF as well as HGF induced a PI3k-dependent activation of pro-uPA when bound to uPAR, which led to an increase in cell surface fibrinolytic activity. As a consequence, uPAR became internalised and redistributed via LDLR-proteins. Interference with these events led to a reduced migratory response of endothelial cells towards VEGF in vitro as well as endothelial cell invasion in vivo. These data give first evidence that the uPA-system, which represents the only level-of-evidence-1 cancer biomarker system for prognosis and/or prediction in node negative breast cancer, might directly affect (tumour-) angiogenesis. PMID- 22782501 TI - [Indications and limitations of fresh frozen sections in the pulmonary apparatus]. AB - Recommendations for the diagnosis of lung tumors almost limit the use of fresh frozen sections to the evaluation of resection margins. In pathology pretherapeutic methods for assessment of clinically suspected lung cancer are favored over intraoperative frozen section diagnosis. For the interdisciplinary management of uncertain lung findings diagnostic methods, such as cytopathology and examination of biopsy material are available. The use of rapid on-site evaluation (ROSE) in cytopathology is limited due to the lack of necessary personnel. Diagnosis of unclear pulmonary lesions or distinction of metastases from primary lung tumors by intraoperative frozen sections is therefore limited to exceptional cases that were not resolved by preoperative biopsies. Such rare cases require a common consensus strategy between thoracic surgeons and pathologists in a preoperative tumor board. PMID- 22782502 TI - Molecular mechanisms of vitamin D action. AB - The hormonal metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1,25D), initiates biological responses via binding to the vitamin D receptor (VDR). When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D. By recruiting complexes of either coactivators or corepressors, ligand-activated VDR-RXR modulates the transcription of genes encoding proteins that promulgate the traditional functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. Thus, vitamin D action in a particular cell depends upon the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP(9k), and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption. VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling. Finally, alternative, low-affinity, non-vitamin D VDR ligands, e.g., lithocholic acid, docosahexaenoic acid, and curcumin, have been reported. Combined alternative VDR ligand(s) and 1,25D/VDR control of gene expression may delay chronic disorders of aging such as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer. PMID- 22782503 TI - Developing novel prognostic biomarkers for multivariate fracture risk prediction algorithms. AB - Multivariate prediction algorithms such as FRAX(r) and QFractureScores provide an opportunity for new prognostic biomarkers to be developed and incorporated, potentially leading to better fracture prediction. As more research is conducted into these novel biomarkers, a number of factors need to be considered for their successful development for inclusion in these algorithms. In this review, we describe two well-known multivariate prediction algorithms for osteoporosis fracture risk applicable to the UK population, FRAX and QFractureScores, and comment on the current prognostic tools available for fracture risk; dual X-ray assessment, quantitative ultrasonography, and genomic/biochemical markers. We also highlight the factors that need to be considered in the development of new biomarkers. These factors include the requirement for prospective data, collected in new cohort studies or using archived samples; the need for adequate stability data to be provided; and the need for appropriate storage methods to be used when retrospective data are required. Area under the receiver operating characteristic curve measures have been found to have limited utility in assessing the impact of the addition of new risk factors on the predictive performance of multivariate algorithms. New performance evaluation measures, such as net reclassification index and integrated discrimination improvement, are increasingly important in the evaluation of the impact of the addition of new markers to multivariate algorithms, and these are also discussed. PMID- 22782505 TI - Synthesis and studies on the anticonvulsant activity of 5-alkoxy [1,2,4]triazolo[4,3-a]pyridine derivatives. AB - In this study, a series of new 5-alkoxy-[1,2,4]triazolo[4,3-a]pyridine derivatives was synthesized and their anticonvulsant activity and neurotoxicity was evaluated with the maximal electroshock and rotarod tests, respectively. The most promising compounds, 3p (5-(4-chlorophenoxy)-[1,2,4]triazolo[4,3-a]pyridine) and 3r (5-(4-bromophenoxy)-[1,2,4]triazolo[4,3-a]pyridine), showed a median effective dose of 13.2 and 15.8 mg/kg and had a protective index value of 4.8 and 6.9, respectively. For exploring the putative mechanism of action, compounds 3n, 3p and 3r were tested in chemically induced models. PMID- 22782504 TI - Loss of expression of the differentially expressed in adenocarcinoma of the lung (DAL-1) protein is associated with metastasis of non-small cell lung carcinoma cells. AB - The differentially expressed in adenocarcinoma of the lung-1 (DAL-1) protein is a member of the membrane-associated cytoskeleton protein 4.1 family. This protein was previously found to be downregulated or lost in more than half of primary non small cell lung cancers (NSCLC). In this study, the relationship between DAL-1 expression and NSCLC metastasis was examined. DAL-1 mRNA and protein levels were measured in NSCLC cell lines and in tumor cells isolated from the pleural fluid of NSCLC patients clinically diagnosed with distant metastases to the bone or brain. The results revealed that DAL-1 expression was observed in two (GLC-82 and NCI-H460) out of seven metastatic NSCLC cell lines examined. DAL-1 expression was not observed in the cells isolated from the pleural fluid in nine out of ten patients. Overexpression of DAL-1 in A549 cells, a cell line lacking endogenous DAL-1, inhibited cell migration and invasion by approximately 38 and 48 %, respectively. In contrast, DAL-1 knockdown in NCI-H460 cells enhanced the migration and invasion potential of this cell line 4.6- and 3-fold, respectively. Furthermore, DAL-1 promoter methylation was observed in six of nine pleural fluid NSCLC cell isolates and in two cell lines (A549 and H1299), as evidenced by a lack of endogenous DAL-1. Demethylation in A549 cells successfully restored DAL-1 mRNA and protein expression levels, resulting in a parallel remarkable inhibition of migration and invasion. These results indicated that DAL-1 was pivotal in triggering NSCLC migration and invasion and that loss of DAL-1 expression was due to the epigenetic methylation. PMID- 22782506 TI - Pharmacokinetics of salsalate and salicylic acid in normal and diabetic rats. AB - The pharmacokinetics (PK) of salsalate (SS) and salicylic acid (SA) was assessed in normal Wistar and diabetic Goto-Kakizaki rats. Three PK studies were conducted: (1) PK of SA in normal rats after intravenous dosing of SA at 20, 40, 80 mg/kg. (2) PK of SS and SA in normal rats after oral dosing of SS at 28, 56, 112 mg/kg. (3) PK during 4 months feeding of SS-containing diet in both normal and diabetic rats. The disposition of SS and SA were evaluated simultaneously using a pharmacokinetic model comprising several transit absorption steps and linear and nonlinear dual elimination pathways for SA. The results indicated that the nonlinear elimination pathway of SA only accounted for a small fraction of the total clearance (< 12%) at therapeutic concentrations. A flat profile of SA was observed after oral dosing of SS, particularly at a high dose. The possible reasons for this flat profile were posed. During the SS-diet feeding, the diabetic rats achieved lower blood concentrations of SA than normal rats with a higher apparent clearance (CL/F), possibly due to incomplete (47%) bioavailability. Such CL/F decreased with age in both diabetic and normal rats. The effect of diabetes on SA pharmacokinetics may necessitate increased dosing in the future usage of SS in diabetes. PMID- 22782509 TI - Brain-immune interactions and ischemic stroke: clinical implications. AB - Increasing evidence shows that the central nervous system and the immune system interact in complex ways, and better insight into these interactions may be relevant to the treatment of patients with stroke and other forms of central nervous system injury. Atherosclerosis, autoimmune disease, and physiological stressors, such as infection or surgery, cause inflammation that contributes to vascular injury and increases the risk of stroke. In addition, the immune system actively participates in the acute pathogenesis of stroke. Thrombosis and hypoxia trigger an intravascular inflammatory cascade, which is further augmented by the innate immune response to cellular damage occurring in the parenchyma. This immune activation may cause secondary tissue injury, but it is unclear whether modulating the acute immune response to stroke can produce clinical benefits. Attempts to dampen immune activation after stroke may have adverse effects because central nervous system injury causes significant immunodepression that places patients at higher risk of infections, such as pneumonia. The activation of innate immunity after stroke sets the stage for an adaptive immune response directed against brain antigens. The pathogenic significance of adaptive immunity and its long-term effects on the postischemic brain remains unclear, but it cannot be ruled out that a persistent autoimmune response to brain antigens has deleterious and long-lasting consequences. Further research will be required to determine what role, if any, immunity has in long-term outcomes after stroke, but elucidation of potential mechanisms may open promising avenues for the development of new therapeutics to improve neurological recovery after brain injury. PMID- 22782510 TI - Comparison of imaging biomarkers in the Alzheimer Disease Neuroimaging Initiative and the Mayo Clinic Study of Aging. AB - OBJECTIVE: To determine whether magnetic resonance imaging measurements observed in the Alzheimer Disease Neuroimaging Initiative (ADNI) convenience sample differ from those observed in the Mayo Clinic Study of Aging (MCSA) population-based sample. DESIGN: Comparison of 2 samples. SETTING: Fifty-nine recruiting sites for the ADNI in the United States and Canada and the MCSA, a population-based cohort in Olmsted County, Minnesota. PATIENTS: Cognitively normal subjects and amnestic subjects with mild cognitive impairment were selected from the ADNI convenience cohort and MCSA population-based cohort. A simple random sample of subjects from both cohorts in the same age range was selected, and a second sample applied matching for age, sex, educational level, apolipoprotein E genotype, and Mini Mental State Examination score. MAIN OUTCOME MEASURES: Baseline hippocampal volumes and annual percentage of decline in hippocampal volume. RESULTS: In the population-based sample, MCSA subjects were older, had less education, performed worse on the Mini-Mental State Examination, and had a family history of Alzheimer disease less often than did ADNI subjects. Baseline hippocampal volumes were larger in ADNI compared with MCSA cognitively normal subjects in the random sample, although no differences were observed after matching. Rates of decline in hippocampal volume were greater in the ADNI compared with the MCSA for cognitively normal subjects and those with amnestic mild cognitive impairment, even after matching. CONCLUSIONS: Rates of decline in hippocampal volume suggest that ADNI subjects have a more aggressive brain pathologic process than MCSA subjects and hence may not be representative of the general population. These findings have implications for treatment trials that use ADNI-like recruitment mechanisms and for studies validating new diagnostic criteria for Alzheimer disease in its various stages. PMID- 22782513 TI - Congenital megaconial myopathy due to a novel defect in the choline kinase Beta gene. AB - OBJECTIVES: To describe the first American patient with a congenital muscle dystrophy characterized by the presence in muscle of gigantic mitochondria displaced to the periphery of the fibers and to stress the potential origin and effects of the mitochondrial changes. DESIGN: Case report and documentation of a novel mutation in the gene encoding choline kinase beta (CHKB). SETTING: Collaboration between 2 tertiary care academic institutions. PATIENT: A 2-year old African American boy with weakness and psychomotor delay. INTERVENTIONS: Detailed clinical and laboratory studies, including muscle biopsy, biochemical analysis of the mitochondrial respiratory chain, and sequencing of the CHKB gene. MAIN OUTCOME MEASURES: Definition of unique mitochondrial changes in muscle. RESULTS: This patient had the same clinical and laboratory features reported in the first cohort of patients, but he harbored a novel CHKB mutation and had isolated cytochrome c oxidase deficiency in muscle. CONCLUSIONS: Besides confirming the phenotype of CHKB mutations, we propose that this disorder affects the mitochondria-associated membrane and the impaired phospholipid metabolism in the mitochondria-associated membrane causes both the abnormal size and displacement of muscle mitochondria. PMID- 22782514 TI - Severe decrease in cerebral blood volume, recanalization, and hemorrhagic transformation after thrombolysis. PMID- 22782511 TI - Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5. AB - BACKGROUND: Familial dyskinesia with facial myokymia (FDFM) is an autosomal dominant disorder that is exacerbated by anxiety. In a 5-generation family of German ancestry, we previously mapped FDFM to chromosome band 3p21-3q21. The 72.5 Mb linkage region was too large for traditional positional mutation identification. OBJECTIVE: To identify the gene responsible for FDFM by exome resequencing of a single affected individual. PARTICIPANTS: We performed whole exome sequencing in 1 affected individual and used a series of bioinformatic filters, including functional significance and presence in dbSNP or the 1000 Genomes Project, to reduce the number of candidate variants. Co-segregation analysis was performed in 15 additional individuals in 3 generations. MAIN OUTCOME MEASURES: Unique DNA variants in the linkage region that co-segregate with FDFM. RESULTS: The exome contained 23 428 single-nucleotide variants, of which 9391 were missense, nonsense, or splice site alterations. The critical region contained 323 variants, 5 of which were not present in 1 of the sequence databases. Adenylyl cyclase 5 (ADCY5) was the only gene in which the variant (c.2176G>A) was co-transmitted perfectly with disease status and was not present in 3510 control white exomes. This residue is highly conserved, and the change is nonconservative and predicted to be damaging. CONCLUSIONS: ADCY5 is highly expressed in striatum. Mice deficient in Adcy5 develop a movement disorder that is worsened by stress. We conclude that FDFM likely results from a missense mutation in ADCY5. This study demonstrates the power of a single exome sequence combined with linkage information to identify causative genes for rare autosomal dominant mendelian diseases. PMID- 22782515 TI - Two faces of the same coin: benign familial infantile seizures and paroxysmal kinesigenic dyskinesia caused by PRRT2 mutations. PMID- 22782516 TI - Insulin and Alzheimer disease. PMID- 22782518 TI - Multivariate detection of gene-gene interactions. AB - Unraveling the nature of genetic interactions is crucial to obtaining a more complete picture of complex diseases. It is thought that gene-gene interactions play an important role in the etiology of cancer, cardiovascular, and immune mediated disease. Interactions among genes are defined as phenotypic effects that differ from those observed for independent contributions of each gene, usually detected by univariate logistic regression methods. Using a multivariate extension of linkage disequilibrium (LD), we have developed a new method, based on distances between sample covariance matrices for groups of single nucleotide polymorphisms (SNPs), to test for interaction effects of two groups of genes associated with a disease phenotype. Since a disease-associated interacting locus will often be in LD with more than one marker in the region, a method that examines a set of markers in a region collectively can offer greater power than traditional methods. Our method effectively identifies interaction effects in simulated data, as well as in data on the genetic contributions to the risk for graft-versus-host disease following hematopoietic stem cell transplantation. PMID- 22782519 TI - Spatial relationships between lead sources and children's blood lead levels in the urban center of Indianapolis (USA). AB - Urban children remain disproportionately at risk of having higher blood lead levels than their suburban counterparts. The Westside Cooperative Organization (WESCO), located in Marion County, Indianapolis, Indiana, has a history of children with high blood lead levels as well as high soil lead (Pb) values. This study aims at determining the spatial relationship between soil Pb sources and children's blood lead levels. Soils have been identified as a source of chronic Pb exposure to children, but the spatial scale of the source-recipient relationship is not well characterized. Neighborhood-wide analysis of soil Pb distribution along with a furnace filter technique for sampling interior Pb accumulation for selected homes (n = 7) in the WESCO community was performed. Blood lead levels for children aged 0-5 years during the period 1999-2008 were collected. The study population's mean blood lead levels were higher than national averages across all ages, race, and gender. Non-Hispanic blacks and those individuals in the Wishard advantage program had the highest proportion of elevated blood lead levels. The results show that while there is not a direct relationship between soil Pb and children's blood lead levels at a spatial scale of ~100 m, resuspension of locally sourced soil is occurring based on the interior Pb accumulation. County-wide, the largest predictor of elevated blood lead levels is the location within the urban core. Variation in soil Pb and blood lead levels on the community level is high and not predicted by housing stock age or income. Race is a strong predictor for blood lead levels in the WESCO community. PMID- 22782521 TI - Excitation energies of retinal chromophores: critical role of the structural model. AB - We employ a variety of highly-correlated approaches including quantum Monte Carlo (QMC) and the n-electron valence state perturbation theory (NEVPT2) to compute the vertical excitation energies of retinal protonated Schiff base (RPSB) models in the gas phase. We find that the NEVPT2 excitation energies are in good agreement with the QMC values and confirm our previous findings that the complete active-space perturbation (CASPT2) approach yields accurate excitations for RPSB models only when the more recent zero-order IPEA Hamiltonian is employed. The excitations computed with the original zero-order formulation of CASPT2 are instead systematically red-shifted by more than 0.3 eV. We then focus on the full 11-cis retinal chromophore and show that the M06-2X and MP2 approaches provide reliable ground-state equilibrium structures for this system while the complete active-space self-consistent field (CASSCF) geometry is characterized by significantly higher ground-state energies at the NEVPT2 and CASPT2 level. Our calibration of the structural model together with the general agreement of all highly-correlated excited-state methods allows us to reliably assign a value of about 2.3 eV to the vertical excitation of 11-cis RPSB in the gas-phase. PMID- 22782520 TI - Cost-effectiveness of disease-modifying therapies in multiple sclerosis. AB - Multiple sclerosis (MS) is a leading cause of disability among young adults and has a significant economic impact on society. Although MS is not currently a curable disease, costly treatments known as disease-modifying therapies (DMTs) are available to reduce the disease impact in certain types of MS. In the current economic downturn, cost-effectiveness analysis (CEA) of therapies in MS has become an important part of the decision-making process in order to use resources efficiently in the face of the rapidly escalating costs of MS. While some studies have reported costs of DMTs at the level of cost-effectiveness thresholds, some have estimated their costs beyond the tolerance level of health care systems. On the basis of the current literature and given the difficulties in accurately assessing cost-effectiveness in diseases like MS, it is challenging to determine whether DMTs are cost-effective. Further population-based studies are required regarding the cost-effectiveness of therapies in MS. PMID- 22782522 TI - Rapid microfluidic screening of CO2 solubility and diffusion in pure and mixed solvents. AB - We present a high-throughput method to determine rapidly and simultaneously the solubility and the diffusivity of CO(2) in pure solvents and mixtures using segmented flow in a microchannel. Gas bubbles are injected via a T-junction into the liquid stream and the evolution of the bubbles' lengths are followed visually. We measure both solubility and diffusion coefficient from the shrinkage and expansion of the bubbles. The presented method is used to study the physical absorption of CO(2) in various pure solvents and to screen the complete composition space of binary and ternary mixtures. PMID- 22782523 TI - Child safety seat usage errors in under-4s. AB - OBJECTIVE: To analyze child safety seat usage errors among children enrolled at daycare. METHODS: This was a cross-sectional, observational study with prospective data collection and a retrospective analytical axis. RESULTS: Overall, 42.7% of the children studied were in incorrectly used seats. A logistic regression model showed that the likelihood of usage errors was higher if there were two or more children in the vehicle (odds ratio = 5.10, p = 0.007) and was dependent on parents' educational level and income (medium income and educational level: odds ratio = 7.00, p = 0.003; low income and educational level: odds ratio = 3.40, p = 0.03). CONCLUSION: The results of this study are in line with findings reported in international publications. PMID- 22782524 TI - Epidemiology of the influenza A virus H5N1 subtype and memory of immunity to the H2N2 subtype. PMID- 22782525 TI - PanM, an acetyl-coenzyme A sensor required for maturation of L-aspartate decarboxylase (PanD). AB - Coenzyme A (CoA) is essential for cellular chemistry in all forms of life. The pantothenate moiety of CoA is generated from the condensation of pantoate and beta-alanine. beta-Alanine is formed by decarboxylation of l-aspartate catalyzed by PanD, a pyruvoyl enzyme that is synthesized by the cell as an inactive precursor (pro-PanD). Maturation of pro-PanD into PanD occurs via a self-cleavage event at residue Ser25, which forms the catalytic pyruvoyl moiety. We recently reported that Salmonella enterica PanM was necessary for pro-PanD maturation, both in vitro and in vivo. Notably, PanM is annotated as a Gcn5-like N acetyltransferase (GNAT), which suggested that lysine acetylation might be part of the mechanism of maturation. Here we show that PanM lacks acetyltransferase activity and that acetyl-CoA stimulates its activity. Results of experiments with nonhydrolyzable ethyl-CoA and genetically encoded acetyl-lysine-containing PanD support the conclusion that PanM-dependent pro-PanD maturation does not involve an acetyl transfer event. We also show that CoA binding to PanM is needed for in vivo activity and that disruption of CoA binding prevents PanM from interacting with PanD. We conclude that PanM is a GNAT homologue that lost its acetyltransferase activity and evolved a new function as an acetyl-CoA sensor that can trigger the maturation of pro-PanD. IMPORTANCE: Nepsilon-lysine acetylation is increasingly being recognized as a widespread and important form of posttranslational regulation in bacteria. The acetyltransferases that catalyze these reactions are poorly characterized in bacteria. Based on annotation, most bacterial genomes contain several acetyltransferases, but the physiological roles of only a handful have been determined. Notably, a subset of putative acetyltransferases lack residues that are critical for activity in most biochemically characterized acetyltransferases. We show that one such putative acetyltransferase, PanM (formerly YhhK), lacks acetyltransferase activity but functions instead as an acetyl-coenzyme A (CoA) sensor. This work establishes the possibility that, like PanM, other putative acetyltransferases may have evolved new functions while retaining the ability to sense acetyl-CoA. PMID- 22782526 TI - The triple threat of cryptococcosis: it's the body site, the strain, and/or the host. AB - Cryptococcosis is the leading invasive fungal infection in the world today. Over the past century, the causative agents, Cryptococcus neoformans and Cryptococcus gattii, have risen from the status of medical curiosities to common but life threatening central nervous system pathogens. In an elegant experimental pathobiology study of these two organisms carried out by Ngamskulrungroj et al., there are three matters that merit further discussion. First is the question of whether there is a variable specific pathobiology for each yeast strain. Does it make biological and clinical sense to designate C. neoformans and C. gattii as two separate species? Second is the matter of how the organisms differ pathologically at the site of infection. Finally, there is the possibility that the human immune system responds differently to each species. Although no single study can provide definitive mechanistic answers to the important questions, this experimental pathology study and its discussion clearly frame the issues to be dissected. PMID- 22782527 TI - Current state of the development of mesenchymal stem cells into clinically applicable Schwann cell transplants. AB - Schwann cells are critically important in recovery from injuries to the peripheral nervous system, and their absence from the central nervous system (CNS) may be a critical limiting factor in the CNS regeneration capacity. Various types of stem cells have been investigated for their potential to be induced to develop a Schwann cell phenotype, with mesenchymal stem cells (MSCs) being the most promising among them. The methods for inducing MSCs differentiation into Schwann cell-like cells are presented in detail in this review. The evidence related to successful differentiation of MSCs to Schwann cell-like cells is particularly discussed herein, which includes the changes in morphology, phenotype, function, and proteome. The possible explanations for the differentiation of MSCs to Schwann cell-like cells are also presented. Finally, we suggest future research aims which will need to be fulfilled to elucidate the biology of Schwann cell differentiation and MSC transdifferentiation, to enable clinical application of therapeutic differentiated MSC transplantation into nerve injury sites. PMID- 22782528 TI - Selective integrin subunit reduction disrupts fibronectin extracellular matrix deposition and fibrillin 1 gene expression. AB - Integrins are transmembrane receptors that can specifically bind extracellular matrix (ECM) proteins. Assembly of the ECM protein fibronectin into fibrils has been shown to be a cell-mediated process that requires integrins. Like fibronectin, fibrillin 1 is an ECM glycoprotein that can assemble into fibrils, but the role of integrins in fibril formation is not understood. To investigate the role of integrins in fibrillin 1 ECM deposition, cells that normally produce and assemble fibrillin 1 fibers in vitro were stably transfected with plasmid constructs encoding short interfering RNAs that target specific integrin subunits. Cells that were deficient in alpha2- and beta3-integrin subunits produced and deposited fibronectin normally, but cells that were deficient for alpha5 and alphaV were unable to elaborate a fibronectin matrix, although they continued to produce and secrete the protein. Surprisingly, the cells that were unable to elaborate a fibronectin matrix also lost fibrillin 1 gene expression. PMID- 22782529 TI - No differences in cancer screening rates in patients with rheumatoid arthritis compared to the general population. AB - OBJECTIVE: Previous study findings have suggested that patients with chronic diseases such as rheumatoid arthritis (RA) do not receive optimal preventive medical services, including cancer screening tests. This study was undertaken to evaluate cancer screening rates in RA patients compared to non-RA control populations. METHODS: Using data from a large US commercial insurance plan, we examined rates of screening tests for cervical, breast, and colon cancer in patients with RA compared to control subjects without RA (non-RA controls) or control subjects with hypertension. Individuals were included in the RA cohort if they had at least 2 visits coded for a diagnosis of RA and had received at least 1 prescription for a disease-modifying antirheumatic drug during the study period. Multivariable Cox proportional hazards models were used to compare the rates of different cancer screening tests between RA patients and non-RA controls. RESULTS: RA patients (n = 13,314) and control subjects (non-RA and hypertension controls) (n = 212,324) were screened, on average, once every 3 years for cervical cancer and once every 2 years for breast cancer during the followup period (mean 2.3 years of followup). In the age-adjusted Cox regression model, women with RA were more likely to receive >= 1 Papanicolaou smear (hazard ratio [HR] 1.21, 95% confidence interval [95% CI] 1.17-1.24), >= 1 mammogram (HR 1.49, 95% CI 1.45-1.53), and >= 1 colonoscopy (HR 1.69, 95% CI 1.61-1.77) compared to female non-RA control subjects. Men with RA were also more likely to receive at least 1 colonoscopy (HR 1.52, 95% CI 1.40-1.64) than were male non-RA control subjects. These results were robust in multivariable analyses adjusted for age, number of physician visits, percentage of visits made to primary care physicians, and the Charlson Comorbidity Index. CONCLUSION: Patients with RA did not appear to be at risk for receiving fewer cancer screening tests when compared to individuals without RA. The majority of both RA patients and non-RA control subjects were screened regularly for cervical, breast, and colon cancer, in accordance with current recommendations. PMID- 22782530 TI - Oxidative stress and platelet activation in subjects with moderate hyperhomocysteinaemia due to MTHFR 677 C->T polymorphism. AB - The methylenetetrahydrofolate reductase (MTHFR) 677 C->T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid peroxidation and platelet activation in carriers of the MTHFR 677 C->T polymorphism and in non-carriers, in relation to tHcy and folate levels. A cross sectional comparison of urinary 8-iso-prostaglandin (PG)F(2alpha) and 11-dehydro thromboxane (TX)B(2) (markers of in vivo lipid peroxidation and platelet activation, respectively) was performed in 100 carriers and 100 non-carriers of the polymorphism. A methionine-loading test and folic acid supplementation were performed to investigate the causal relationship of the observed associations. Urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB(2) were higher in carriers with hyperhomocysteinaemia than in those without hyperhomocysteinaemia (p<0.0001). Hyperhomocysteinaemic carriers had lower folate levels (p=0.0006), higher urinary 8-iso-PGF(2alpha) (p<0.0001) and 11-dehydro-TXB(2) (p<0.0001) than hyperhomocysteinaemic non-carriers. On multiple regression analysis, high tHcy (p<0.0001), low folate (p<0.04) and MTHFR 677 C->T polymorphism (p<0.001) independently predicted high rates of 8-iso-PGF(2alpha) excretion. Methionine loading increased plasma tHcy (p=0.002), and both urinary prostanoid metabolites (p=0.002). Folic acid supplementation was associated with decreased urinary 8-iso PGF(2alpha) and 11-dehydro-TXB2 excretion (p<0.0003) in the hyperhomocysteinaemic group, but not in the control group, with substantial inter-individual variability related to baseline tHcy level and the extent of its reduction. In conclusion, hyperhomocysteinaemia due to the MTHFR 677 C->T polymorphism is associated with enhanced in vivo lipid peroxidation and platelet activation that are reversible, at least in part, following folic acid supplementation. An integrated biomarker approach may help identifying appropriate candidates for effective folate supplementation. PMID- 22782531 TI - Spontaneous tendon rupture of the extensor digitrum communis in systemic lupus erythematosus. AB - We present a rare case of spontaneous tendon rupture of the extensor digitorum communis (EDC) in a patient with systemic lupus erythematosus (SLE). Inflammation in SLE presents as periarthritis, which may develop into Jaccoud's arthropathy. We bridged the ruptured tendon of the EDC (III) at the metacarpophalangeal (MP) joint of this patient with a tendon graft. This case demonstrates that this portion of the MP joint can be a site of tendon rupture of fingers in SLE patients. PMID- 22782532 TI - IKZF1: a critical role in the pathogenesis of systemic lupus erythematosus? AB - Ikaros family zinc finger 1, encoded by IKZF1, are lymphoid-restricted zinc finger transcription factors that share common N-terminal Kruppel-like zinc finger DNA-binding domain. IKZF1 play multiple important roles on regulators of lymphocyte differentiation and hematological tumor suppressor. Our genome-wide association (GWA) studies in systemic lupus erythematosus (SLE) independently identified genetic variants in IKZF1 associated with SLE, which are supported by other studies. Previous studies found that lower expression of IKZF1 may play critical roles in activating some signal pathways involved in SLE, such as signal transducers and activators of transcription (STAT)4 and interferon pathways. In addition, IKZF1 has been implicated in roles involved in some hematologic traits or abnormalities, such as erythrocyte measures, myelofibrosis, and acute lymphoblastic leukemia (ALL), which may be common clinical manifestations or co occurrence hematological diseases of patients with SLE. All these findings suggest that IKZF1 may play a critical role in the pathogenesis of SLE. In this article, we discuss the existing understanding of the role of IKZF1 on the physiological and pathological functions associated with SLE, providing insights that may assist in the development of new therapeutic strategies based on IKZF1 for patients with SLE. PMID- 22782533 TI - Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab. AB - Neuromyelitis optica (NMO) is a disabling autoimmune disease associated with an elevation of anti-aquaporin 4 (AQP4) autoantibodies. Here, we present a case with NMO who responded to monthly administration of the anti-IL-6 receptor antibody tocilizumab. The treatment rapidly reduced the elevated numbers of plasmablasts and anti-AQP4 autoantibodies in the patient. Furthermore, neuropathic pain and disability scores gradually improved. Tocilizumab may be considered as a therapeutic option for NMO. PMID- 22782534 TI - Excretion profile of hydrocodone, hydromorphone and norhydrocodone in urine following single dose administration of hydrocodone to healthy volunteers. AB - Abuse of prescription opioids for non-medical use has been on the rise over the past decade. The most commonly abused opioid is hydrocodone, a frequently prescribed pain medication metabolized by the body to hydromorphone, norhydrocodone and other minor metabolites. This study describes the excretion profile of hydrocodone, hydromorphone and norhydrocodone in urine following a single dose (10 mg) administration of hydrocodone to human subjects (n = 7) and presents a validated liquid chromatography-tandem mass spectrometry method for analysis of the drug and its metabolites. Limit of quantitation was 5 ng/mL for all analytes; limit of detection was 2.5 ng/mL for hydrocodone and norhydrocodone and 5 ng/mL for hydromorphone. Peak concentrations of hydrocodone were found at 3:30-7:00 hours post-dose and were in the range of 612-2,190 ng/mL. Hydromorphone peak concentrations were found at 6:15-26:45 hours post-dose and ranged from 102 to 342 ng/mL. For norhydrocodone, peak concentrations were found at 4:20-13:00 hours post-dose and ranged from 811 to 3,460 ng/mL. Although hydromorphone was found at lower levels than hydrocodone, in six of seven subjects, it persisted for as long as hydrocodone was detected. Norhydrocodone was found at higher levels and lasted for a longer period of time than hydrocodone, thus making the nor-metabolite a valuable tool in evaluating hydrocodone use and/or misuse. PMID- 22782535 TI - Synthesis and anticoagulant activity of bioisosteric sulfonic-Acid analogues of the antithrombin-binding pentasaccharide domain of heparin. AB - Two pentasaccharide sulfonic acids that were related to the antithrombin-binding domain of heparin were prepared, in which two or three primary sulfate esters were replaced by sodium-sulfonatomethyl moieties. The sulfonic-acid groups were formed on a monosaccharide level and the obtained carbohydrate sulfonic-acid esters were found to be excellent donors and acceptors in the glycosylation reactions. Throughout the synthesis, the hydroxy groups to be methylated were masked in the form of acetates and the hydroxy groups to be sulfated were masked with benzyl groups. The disulfonic-acid analogue was prepared in a [2+3] block synthesis by using a trisaccharide disulfonic acid as an acceptor and a glucuronide disaccharide as a donor. For the synthesis of the pentasaccharide trisulfonic acid, a more-efficient approach, which involved elongation of the trisaccharide acceptor with a non-oxidized precursor of the glucuronic acid followed by post-glycosidation oxidation at the tetrasaccharide level and a subsequent [1+4] coupling reaction, was elaborated. In vitro evaluation of the anticoagulant activity of these new sulfonic-acid derivatives revealed that the disulfonate analogue inhibited the blood-coagulation-proteinase factor Xa with outstanding efficacy; however, the introduction of the third sulfonic-acid moiety resulted in a notable decrease in the anti-Xa activity. The difference in the biological activity of the disulfonic- and trisulfonic-acid counterparts could be explained by the different conformation of their L-iduronic-acid residues. PMID- 22782536 TI - Within-plant distribution of cotton aphid (Hemiptera: Aphididae) in cotton cultivars with colored fibers. AB - We describe the vertical and horizontal distribution of the cotton aphid Aphis gossypii Glover within a cotton plant in two cotton (Gossypium hirsutum Linnaeus) cultivars (BRS Safira and BRS Rubi) with colored fiber over the time. Measurements of aphid population dynamics and distribution in the cotton plants were recorded in intervals of seven days. The number of apterous or alate aphids and their specific locations were recorded, using as a reference point the location of nodes on the mainstem of the plant and also those on the leaves present on branches and fruit structures. The number of apterous aphids found on the cultivar BRS Safira (56,515 aphids) was greater than that found on BRS Rubi (50,537 aphids). There was no significant difference between the number of alate aphids found on the cultivars BRS Safira (365 aphids/plant) and BRS Rubi (477 aphids/plant). There were interactions between cotton cultivar and plant age, between plant region and plant age, and between cultivar and plant region for apterous aphids. The results of this study are of great importance in improving control strategies for A. gossypii in the naturally-colored cotton cultivars BRS Safira and BRS Rubi. PMID- 22782537 TI - Variations in the abundance of three Parulidae species in the southern portion of the Brazilian Atlantic Forest, state of Parana. AB - We evaluated the distribution of abundance of three species of warblers in the southern portion of the Brazilian Atlantic Forest (BAF): Tropical Parula (Parula pitiayumi), the Golden-Crowned Warbler (Basileuterus culicivorus) and the White Rimmed Warbler (Basileuterus leucoblepharus). Three types of forests comprise this region of the Atlantic Forest: seasonal semi-deciduous forest (SF), mixed rain forest (MF) and dense rain forest (DF). These forest types occur at different elevations: SF ranging from 200 to 800 m, MF ranging from 800 to 1,200 m and DF ranging from sea level up to 2,000 m. We used point counts in fifteen study areas distributed in the three forest types. The White-Rimmed Warbler and the Tropical Parula had higher abundances in MF, and their abundance was positively correlated with the elevation. The Golden-Crowned Warbler did not present a significant difference in abundance among the forest types, and no correlation between abundance and elevation was found. We suggest that the difference in the occupancy of the forest strata by the Golden-Crowned Warbler is because this species is more generalist and thus less sensitive to variations in the vegetation structure among the forests types when compared to the other two warbler species. PMID- 22782538 TI - Source correlation of biomarkers in a mangrove ecosystem on Santa Catarina Island in southern Brazil. AB - The relative distribution of several compounds identified in four samples of recently deposited sediments of the Itacorubi Mangrove located on the Santa Catarina Island, southern Brazil, was compared with similar data on compounds extracted from fresh leaves of three mangrove species (Avicennia schaueriana, the dominant species in the area, Rhizophora mangle and Laguncularia racemosa) and the Gramineae Spartinna alterniflora. Terpenols, previously identified in mangrove species in northern Brazil, were also found. A. schaueriana mainly contains beta-amyrin (90.6 MUg g(-1) of extractable organic matter); low amounts of friedelin, betulin and germanicol were detected only in the leaf extract of this species. R. mangle also contained a significant amount of beta-amyrin and it was the only species where taraxerol was detected. In contrast to the leaves, sediment extracts were dominated by germanicol, alpha-amyrin and campesterol. Despite its chemical lability, betulin was also detected. Two homologous series of alpha and omega-hydroxy fatty acids were detected in the acid-alkaline fraction. In spite of being reported in the literature as components of terrigenous plants, saturated omega-hydroxy acids were not identified. Our results indicate that although triterpenols may be used as biomarkers for mangrove-derived organic matter, their relative distribution can change according to the region. PMID- 22782540 TI - Microwave-assisted deacylation of unactivated amides using ammonium-salt accelerated transamidation. AB - The combination of an ammonium salt and ethylenediamine promotes deacylation of a variety of unactivated amides to give the corresponding amines in high yields without the use of strong acids or bases. The reactions proceed without special care regarding air and moisture, and tolerate a wide range of functional groups. PMID- 22782539 TI - Pharmacokinetic and pharmacodynamic effects of comedication of clopidogrel and dabigatran etexilate in healthy male volunteers. AB - PURPOSE: To evaluate the pharmacokinetic and pharmacodynamic effects of concomitant administration of single loading doses of clopidogrel or multiple doses of clopidogrel with multiple doses of dabigatran etexilate. METHODS: This was an open-label trial in healthy male subjects. In part 1 (pilot, n = 8) and part 3 (n = 12), a single dose of clopidogrel (300 or 600 mg, respectively) was given concomitantly with dabigatran etexilate at steady state; part 2 was a randomized, multiple-dose, crossover study with the test treatment being clopidogrel at steady state [300 mg loading dose on day 1, then 75 mg once daily (qd)] with concomitant dabigatran. RESULTS: Bioavailability was moderately increased when a loading dose of clopidogrel (300 mg in part 1 and 600 mg in part 3) was administered concomitantly with dabigatran etexilate 150 mg twice daily (bid). Test/reference ratios for AUC(tau,ss) were 135% (90% CI 107-169%) and 132% (90% CI 112-156%), respectively. Steady-state dosing of clopidogrel 75 mg qd and dabigatran etexilate 150 mg bid (part 2) demonstrated minor effects on dabigatran pharmacokinetics (AUC(tau,ss) ratio test/reference: 91.9%, 90% CI 78.7-107%) or its pharmacokinetic/pharmacodynamic relationships (activated partial thromboplastin time, ecarin clotting time, thrombin time). Similarly, clopidogrel bioavailability remained unchanged by chronic administration of dabigatran etexilate (part 3: ratio test/reference for AUC(0-24) was 103%; 90% CI 80.3 131%), as did its pharmacodynamic effects on the inhibition of platelet aggregation. CONCLUSIONS: When given concomitantly, dabigatran etexilate and clopidogrel at clinically relevant doses did not appear to have significant effects on the pharmacokinetic and pharmacodynamic profiles of either agent. PMID- 22782541 TI - Endoplasmic reticulum aminopeptidase 1 and interleukin-23 receptor in ankylosing spondylitis. AB - Endoplasmic reticulum aminopeptidase 1 (ERAP1) and interleukin-23 receptor (IL 23R) gene polymorphisms were found to be associated with ankylosing spondylitis (AS) in a nonsynonymous single nucleotide polymorphism association study, and this has been replicated in several studies across different populations. ERAP1 variants could lead to significant changes in the repertoire of peptides presented by MHC-I. Reading this in conjunction with the known association of AS with HLA-B27, a functional interaction between ERAP1 and HLA-B27 is very likely. ERAP1 has additionally been shown to be involved in cytokine receptor shedding. The IL-23R is one of the two receptors that mediate the action of IL-23. AS is associated with the same polymorphisms of IL-23R as those linked to psoriasis and inflammatory bowel disease. This suggests common genetic risks linking AS and extra-articular manifestations. This review focuses on the pathogenic potential of these two genes in AS. PMID- 22782542 TI - Effects of anxiolytic treatment on potentiated startle during aversive image anticipation. AB - OBJECTIVE: Heightened anticipation of future events has been characterized as a feature of certain anxiety disorders. In functional magnetic resonance imaging studies, anticipation of fearful/threatening images has been shown to robustly activate the insular cortex and amygdala in healthy subjects, in subjects with high trait anxiety, and in some with anxiety disorders. Blood oxygenation level dependent activation in response to negative image anticipation is also sensitive to anxiolytic treatment, suggesting that image anticipation probes anxiety systems. It is not clear, however, if behavioral responses to image anticipation are also sensitive to anxiolytics. This study tested the hypothesis that anxiety behaviors during anticipation of negative images are sensitive to anxiolytic treatment. METHOD: This study examined the effects of alprazolam and pregabalin treatment on potentiated startle during affective image anticipation. RESULTS: There was an effect of anticipation type (negative versus neutral versus positive) on startle reactivity and subjective ratings, suggesting that the task was effective in assaying negative anticipatory arousal. Both treatments significantly reduced overall startle magnitude. However, neither treatment specifically affected potentiated startle during aversive anticipation. CONCLUSION: These data suggest that potentiated startle in response to anticipation of aversive images is not sensitive to anxiolytic treatments in a healthy population, limiting its use as a predictive model of anxiolytic activity. This article is a US Government work and is in the public domain in the USA. PMID- 22782544 TI - Separation of two phenotypically similar cell types via a single common marker in microfluidic channels. AB - To isolate clinically and biologically relevant cell types from a heterogeneous population, fluorescent or magnetic tagging together with knowledge of surface biomarker profiles represents the state of the art. To date, it remains exceedingly difficult to separate phenotypically and physically similar cell types from a mixed population. We report a microfluidic platform engineered to separate two highly similar cell types using a single antibody by taking advantage of subtle variations in surface receptor density and cell size. This platform utilizes antibody-conjugated surfaces in microfluidic channels together with precise modulation of fluid shear stresses to accomplish selective fractionation in a continuous flow process. Antibody conjugation density variation on the adhesive surfaces is achieved by covalently immobilizing an antibody in the presence of poly(ethylene glycol). This platform is used to demonstrate separation of two CD31 positive cell types, human umbilical vein endothelial cells and human micro vascular endothelial cells. PMID- 22782543 TI - Potential fluid mechanic pathways of platelet activation. AB - Platelet activation is a precursor for blood clotting, which plays leading roles in many vascular complications and causes of death. Platelets can be activated by chemical or mechanical stimuli. Mechanically, platelet activation has been shown to be a function of elevated shear stress and exposure time. These contributions can be combined by considering the cumulative stress or strain on a platelet as it is transported. Here, we develop a framework for computing a hemodynamic-based activation potential that is derived from a Lagrangian integral of strain rate magnitude. We demonstrate that such a measure is generally maximized along, and near to, distinguished material surfaces in the flow. The connections between activation potential and these structures are illustrated through stenotic flow computations. We uncover two distinct structures that may explain observed thrombus formation at the apex and downstream of stenoses. More broadly, these findings suggest fundamental relationships may exist between potential fluid mechanic pathways for mechanical platelet activation and the mechanisms governing their transport. PMID- 22782545 TI - Computational prediction of N-linked glycosylation incorporating structural properties and patterns. AB - MOTIVATION: N-linked glycosylation occurs predominantly at the N-X-T/S motif, where X is any amino acid except proline. Not all N-X-T/S sequons are glycosylated, and a number of web servers for predicting N-linked glycan occupancy using sequence and/or residue pattern information have been developed. None of the currently available servers, however, utilizes protein structural information for the prediction of N-glycan occupancy. RESULTS: Here, we describe a novel classifier algorithm, NGlycPred, for the prediction of glycan occupancy at the N-X-T/S sequons. The algorithm utilizes both structural as well as residue pattern information and was trained on a set of glycosylated protein structures using the Random Forest algorithm. The best predictor achieved a balanced accuracy of 0.687 under 10-fold cross-validation on a curated dataset of 479 N-X T/S sequons and outperformed sequence-based predictors when evaluated on the same dataset. The incorporation of structural information, including local contact order, surface accessibility/composition and secondary structure thus improves the prediction accuracy of glycan occupancy at the N-X-T/S consensus sequon. AVAILABILITY AND IMPLEMENTATION: NGlycPred is freely available to non-commercial users as a web-based server at http://exon.niaid.nih.gov/nglycpred/. PMID- 22782546 TI - CytoSPADE: high-performance analysis and visualization of high-dimensional cytometry data. AB - MOTIVATION: Recent advances in flow cytometry enable simultaneous single-cell measurement of 30+ surface and intracellular proteins. CytoSPADE is a high performance implementation of an interface for the Spanning-tree Progression Analysis of Density-normalized Events algorithm for tree-based analysis and visualization of this high-dimensional cytometry data. AVAILABILITY: Source code and binaries are freely available at http://cytospade.org and via Bioconductor version 2.10 onwards for Linux, OSX and Windows. CytoSPADE is implemented in R, C++ and Java. CONTACT: michael.linderman@mssm.edu SUPPLEMENTARY INFORMATION: Additional documentation available at http://cytospade.org. PMID- 22782547 TI - Algorithms and complexity of enumerating minimal precursor sets in genome-wide metabolic networks. AB - MOTIVATION: In the context of studying whole metabolic networks and their interaction with the environment, the following question arises: given a set of target metabolites T and a set of possible external source metabolites , which are the minimal subsets of that are able to produce all the metabolites in T. Such subsets are called the minimal precursor sets of T. The problem is then whether we can enumerate all of them efficiently. RESULTS: We propose a new characterization of precursor sets as the inputs of reaction sets called factories and an efficient algorithm to decide if a set of sources is precursor set of T. We show proofs of hardness for the problems of finding a precursor set of minimum size and of enumerating all minimal precursor sets T. We propose two new algorithms which, despite the hardness of the enumeration problem, allow to enumerate all minimal precursor sets in networks with up to 1000 reactions. AVAILABILITY: Source code and datasets used in our benchmarks are freely available for download at http://sites.google.com/site/pitufosoftware/download. CONTACT: vicente77@gmail.com, pvmilreu@gmail.com or marie-france.sagot@inria.fr. PMID- 22782548 TI - Gemma: a resource for the reuse, sharing and meta-analysis of expression profiling data. AB - Gemma is a database, analysis software system and web site for genomics data re use and meta-analysis. Currently, Gemma contains analyzed data from over 3300 expression profiling studies, yielding hundreds of millions of differential expression results and coexpression patterns (correlated expression) for retrieval and visualization. With optional registration users can save their own data and securely share it with other users. Web services and integration with third-party resources further increase the scope of the tools, which include a Cytoscape plugin. AVAILABILITY: http://chibi.ubc.ca/Gemma, Apache 2.0 license. PMID- 22782549 TI - dbSNO: a database of cysteine S-nitrosylation. AB - S-nitrosylation (SNO), a selective and reversible protein post-translational modification that involves the covalent attachment of nitric oxide (NO) to the sulfur atom of cysteine, critically regulates protein activity, localization and stability. Due to its importance in regulating protein functions and cell signaling, a mass spectrometry-based proteomics method rapidly evolved to increase the dataset of experimentally determined SNO sites. However, there is currently no database dedicated to the integration of all experimentally verified S-nitrosylation sites with their structural or functional information. Thus, the dbSNO database is created to integrate all available datasets and to provide their structural analysis. Up to April 15, 2012, the dbSNO has manually accumulated >3000 experimentally verified S-nitrosylated peptides from 219 research articles using a text mining approach. To solve the heterogeneity among the data collected from different sources, the sequence identity of these reported S-nitrosylated peptides are mapped to the UniProtKB protein entries. To delineate the structural correlation and consensus motif of these SNO sites, the dbSNO database also provides structural and functional analyses, including the motifs of substrate sites, solvent accessibility, protein secondary and tertiary structures, protein domains and gene ontology. AVAILABILITY: The dbSNO is now freely accessible via http://dbSNO.mbc.nctu.edu.tw. The database content is regularly updated upon collecting new data obtained from continuously surveying research articles. PMID- 22782550 TI - MSeasy: unsupervised and untargeted GC-MS data processing. AB - MSeasy performs unsupervised data mining on gas chromatography-mass spectrometry data. It detects putative compounds within complex metabolic mixtures through the clustering of mass spectra. Retention times or retention indices are used after clustering, together with other validation criteria, for quality control of putative compounds. The package generates a fingerprinting or profiling matrix compatible with NIST mass spectral search program and ARISTO webtool (Automatic Reduction of Ion Spectra To Ontology) for molecule identification. Most commonly used file formats, NetCDF, mzXML and ASCII, are acceptable. A graphical and user friendly interface, MSeasyTkGUI, is available for R novices. AVAILABILITY: MSeasy and MSeasytkGUI are implemented as R packages available at http://cran.r project.org/web/packages/MSeasy/index.html and http://cran.r project.org/web/packages/MSeasyTkGUI/index.html. PMID- 22782551 TI - Efficient sampling for Bayesian inference of conjunctive Bayesian networks. AB - MOTIVATION: Cancer development is driven by the accumulation of advantageous mutations and subsequent clonal expansion of cells harbouring these mutations, but the order in which mutations occur remains poorly understood. Advances in genome sequencing and the soon-arriving flood of cancer genome data produced by large cancer sequencing consortia hold the promise to elucidate cancer progression. However, new computational methods are needed to analyse these large datasets. RESULTS: We present a Bayesian inference scheme for Conjunctive Bayesian Networks, a probabilistic graphical model in which mutations accumulate according to partial order constraints and cancer genotypes are observed subject to measurement noise. We develop an efficient MCMC sampling scheme specifically designed to overcome local optima induced by dependency structures. We demonstrate the performance advantage of our sampler over traditional approaches on simulated data and show the advantages of adopting a Bayesian perspective when reanalyzing cancer datasets and comparing our results to previous maximum likelihood-based approaches. AVAILABILITY: An R package including the sampler and examples is available at http://www.cbg.ethz.ch/software/bayes-cbn. CONTACTS: niko.beerenwinkel@bsse.ethz.ch. PMID- 22782553 TI - Correlation between sodium and potassium excretion in 24- and 12-h urine samples. AB - Low-sodium and high-potassium diets have been recommended as an adjunct to prevention and treatment of hypertension. Analysis of these nutrients in 24-h urine has been considered the reference method to estimate daily intake of these minerals. However, 24-h urine collection is difficult in epidemiological studies, since urine must be collected and stored in job environments. Therefore, strategies for shorter durations of urine collection at home have been proposed. We have previously reported that collecting urine during a 12-h period (overnight) is more feasible and that creatinine clearance correlated strongly with that detected in 24-h samples. In the present study, we collected urine for 24 h divided into two 12-h periods (from 7:00 am to 7:00 pm and from 7:00 pm to 7:00 am next day). A sample of 109 apparently healthy volunteers aged 30 to 74 years of both genders working in a University institution was investigated. Subjects with previous myocardial infarction, stroke, renal insufficiency, and pregnant women were not included. Significant (P < 0.001) Spearman correlation coefficients (r s) were found between the total amount of sodium and potassium excreted in the urine collected at night and in the 24-h period (r s = 0.76 and 0.74, respectively). Additionally, the 12-h sodium and potassium excretions (means +/- SD, 95% confidence interval) corresponded to 47.3 +/- 11.2%, 95%CI = 45.3-49.3, and 39.3 +/- 4.6%, 95%CI = 37.3-41.3, respectively, of the 24-h excretion of these ions. Therefore, these findings support the assumption that 12 h urine collected at night can be used as a reliable tool to estimate 24-h intake/excretion of sodium and potassium. PMID- 22782554 TI - Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas. AB - The tumorigenesis of pituitary adenomas is poorly understood. Mutations of the PIK3CA proto-oncogene, which encodes the p110-alpha catalytic subunit of PI3K, have been reported in various types of human cancers regarding the role of the gene in cell proliferation and survival through activation of the PI3K/Akt signaling pathway. Only one Chinese study described somatic mutations and amplification of the PIK3CA gene in a large series of pituitary adenomas. The aim of the present study was to determine genetic alterations of PIK3CA in a second series that consisted of 33 pituitary adenomas of different subtypes diagnosed by immunohistochemistry: 6 adrenocorticotropic hormone-secreting microadenomas, 5 growth hormone-secreting macroadenomas, 7 prolactin-secreting macroadenomas, and 15 nonfunctioning macroadenomas. Direct sequencing of exons 9 and 20 assessed by qPCR was employed to investigate the presence of mutations and genomic amplification defined as a copy number >=4. Previously identified PIK3CA mutations (exon 20) were detected in four cases (12.1%). Interestingly, the Chinese study reported mutations only in invasive tumors, while we found a PIK3CA mutation in one noninvasive corticotroph microadenoma. PIK3CA amplification was observed in 21.2% (7/33) of the cases. This study demonstrates the presence of somatic mutations and amplifications of the PIK3CA gene in a second series of pituitary adenomas, corroborating the previously described involvement of the PI3K/Akt signaling pathway in the tumorigenic process of this gland. PMID- 22782555 TI - Is arterial stiffness in HIV-infected individuals associated with HIV-related factors? AB - We investigated the association between pulse wave velocity (PWV) and HIV infection, antiretroviral treatment-related characteristics, viral load, immune status, and metabolic changes in a cross-sectional study nested in a cohort of HIV/AIDS patients who have been followed for metabolic and cardiovascular changes since 2007. The study included patients recruited from the cohort (N = 261) and a comparison group (N = 82) of uninfected individuals, all enrolled from April to November 2009. Aortic stiffness was estimated using the carotid-femoral PWV (Complior-Artech, Paris, France). The groups were similar with respect to age, metabolic syndrome, diabetes mellitus, Framingham score, and use of antihypertensive and hypolipidemic medications. Hypertension was more frequent among the controls. Individuals with HIV had higher triglyceride, glucose and HDL cholesterol levels. Among individuals with HIV/AIDS, those with a nadir CD4+ T cell count <200 cells/mm3 had a higher PWV (P = 0.01). There was no statistically significant difference when subjects were stratified by gender. Heart rate, age, male gender, and blood pressure were independently correlated with PWV. Nadir CD4+ T-cell count did not remain in the final model. There was no significance difference in PWV between HIV-infected individuals and uninfected controls. PWV was correlated with age, gender, and blood pressure across the entire population and among those infected with HIV. We recommend cohort studies to further explore the association between inflammation related to HIV infection and/or immune reconstitution and antiretroviral use and PWV. PMID- 22782557 TI - In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer. AB - Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 +/- 0.56 and 1.23 +/- 0.42%) in vitro. SWNT THP exhibited higher tumor depression than THP-saline in vitro (74.35 +/- 2.56 and 51.24 +/- 1.45%) and in vivo (52.46 +/- 2.41 and 96.85 +/- 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer. PMID- 22782556 TI - Comparison of the reliability of multifocal visual evoked cortical potentials generated by pattern reversal and pattern pulse stimulation. AB - This study compared the effectiveness of the multifocal visual evoked cortical potentials (mfVEP) elicited by pattern pulse stimulation with that of pattern reversal in producing reliable responses (signal-to-noise ratio >1.359). Participants were 14 healthy subjects. Visual stimulation was obtained using a 60 sector dartboard display consisting of 6 concentric rings presented in either pulse or reversal mode. Each sector, consisting of 16 checks at 99% Michelson contrast and 80 cd/m2 mean luminance, was controlled by a binary m-sequence in the time domain. The signal-to-noise ratio was generally larger in the pattern reversal than in the pattern pulse mode. The number of reliable responses was similar in the central sectors for the two stimulation modes. At the periphery, pattern reversal showed a larger number of reliable responses. Pattern pulse stimuli performed similarly to pattern reversal stimuli to generate reliable waveforms in R1 and R2. The advantage of using both protocols to study mfVEP responses is their complementarity: in some patients, reliable waveforms in specific sectors may be obtained with only one of the two methods. The joint analysis of pattern reversal and pattern pulse stimuli increased the rate of reliability for central sectors by 7.14% in R1, 5.35% in R2, 4.76% in R3, 3.57% in R4, 2.97% in R5, and 1.78% in R6. From R1 to R4 the reliability to generate mfVEPs was above 70% when using both protocols. Thus, for a very high reliability and thorough examination of visual performance, it is recommended to use both stimulation protocols. PMID- 22782558 TI - Modeling the demand for long-term care services under uncertain information. AB - Developing a network of long-term care (LTC) services is currently a health policy priority in many countries, in particular in countries with a health system based on a National Health Service (NHS) structure. Developing such a network requires proper planning and basic information on future demand and utilization of LTC services. Unfortunately, this information is often not available and the development of methods to properly predict demand is therefore essential. The current study proposes a simulation model based on a Markov cycle tree structure to predict annual demand for LTC services so as to inform the planning of these services at the small-area level in the coming years. The simulation model is multiservice, as it allows for predicting the annual number of individuals in need of each type of LTC service (formal and informal home based, ambulatory and institutional services), the resources/services that are required to satisfy those needs (informal caregivers, domiciliary visits, consultations and beds) and the associated costs. The model developed was validated using past data and key international figures and applied to Portugal at the Lisbon borough level for the 2010-2015 period. Given data imperfections and uncertainties related to predicting future LTC demand, uncertainty was modeled through an integrated approach that combines scenario analysis with probabilistic sensitivity analysis using Monte Carlo simulation. Results show that the model provides information critical for informing the planning and financing of LTC networks. PMID- 22782559 TI - Mechanistic investigation of food effect on disintegration and dissolution of BCS class III compound solid formulations: the importance of viscosity. AB - A negative food effect, i.e. a decrease in bioavailability upon the co administration of compounds together with food, has been attributed particularly with high solubility/low permeability compounds (BCS class III). Different mechanisms have been proposed including intestinal dilution leading to a lower concentration gradient across the intestinal wall as well as binding of the active pharmaceutical ingredient to food components in the intestine and thereby decreasing the fraction of the dose available for absorption. These mechanisms refer primarily to the compound and not to the dosage form. An increase in viscosity of the dissolution fluid will in particular affect the absorption of BCS type III compounds with preferential absorption in the upper small intestine if the API release is delayed from the dosage form. The present study demonstrated that the increase in viscosity of the dissolution medium, following ingestion of a solid meal, may drastically reduce disintegration and dissolution. For that purpose the viscosity of the standard FDA meal was determined and simulated by solutions of HPMC in buffer. As model formulations, three commercially available tablets containing trospium chloride, a BCS class III m cholinoreceptor antagonist was used. Trospium chloride drug products have been described to undergo a negative food effect of more than 80% following ingestion with food. The tablets showed prolonged disintegration times and reduced dissolution rates in viscous media, which could be attributed to changes in the liquid penetration rates. The effect was particularly significant for film-coated tablets relative to uncoated dosage forms. The results show the necessity of considering media viscosity when designing in vitro models of drug release for BCS type III drug formulations. PMID- 22782560 TI - Self-assembly of amphipathic beta-sheet peptides: insights and applications. AB - Amphipathic peptides composed of alternating polar and nonpolar residues have a strong tendency to self-assemble into one-dimensional, amyloid-like fibril structures. Fibrils derived from peptides of general (XZXZ)(n) sequence in which X is hydrophobic and Z is hydrophilic adopt a putative beta-sheet bilayer. The bilayer configuration allows burial of the hydrophobic X side chain groups in the core of the fibril and leaves the polar Z side chains exposed to solvent. This architectural arrangement provides fibrils that maintain high solubility in water and has facilitated the recent exploitation of self-assembled amphipathic peptide fibrils as functional biomaterials. This article is a critical review of the development and application of self-assembling amphipathic peptides with a focus on the fundamental insight these types of peptides provide into peptide self assembly phenomena. PMID- 22782561 TI - Aromatic interactions in model peptide beta-hairpins: ring current effects on proton chemical shifts. AB - Crystal structures of eight peptide beta-hairpins in the sequence Boc-Leu-Phe-Val Xxx-Yyy-Leu-Phe-Val-OMe revealed that the Phe(2) and Phe(7) aromatic rings are in close spacial proximity, with the centroid-centroid distance (R(cen)) of 4.4-5.4 A between the two phenyl rings. Proton NMR spectra in chloroform and methanol solution reveal a significant upfield shift of the Phe(7) C(delta,delta') H(2) protons (6.65-7.04 ppm). Specific assignments of the aromatic protons have been carried out in the peptide Boc-Leu-Phe-Val-(D)Pro-(L)Pro-Leu-Phe-Val-OMe (6). The anticipated ring current shifts have been estimated from the aromatic ring geometrics observed in crystals for all eight peptides. Only one of the C(delta,delta') H proton lies in the shielding zone with rapid ring flipping, resulting in averaging between the two extreme chemical shifts. An approximate estimate of the population of conformations, which resemble crystal state orientation, may be obtained. Key nuclear Overhauser effects (NOEs) between facing Phe side chains provide support for close similarity between the solid state and solution conformation. Temperature dependence of aromatic ring proton chemical shift and line widths for peptide 6 (Boc-Leu-Phe-Val-(D)Pro-(L)Pro-Leu Phe-Val-OMe) and the control peptide Boc-Leu-Val-Val-(D)Pro-Gly-Leu-Phe-Val-OMe establish an enhanced barrier to ring flipping when the two Phe rings are in proximity. Modeling studies suggest that small, conformational adjustment about C(alpha)-C(beta) (chi(1) ) and C(beta)-C(gamma) (chi(2) ) bonds of both the Phe residues may be required in order to permit unhindered, uncorrelated flipping of both the Phe rings. The maintenance of the specific aromatic ring orientation in organic solvents provides evidence for significant stabilizing interaction. PMID- 22782562 TI - N-glycosylation of enhanced aromatic sequons to increase glycoprotein stability. AB - N-glycosylation can increase the rate of protein folding, enhance thermodynamic stability, and slow protein unfolding; however, the molecular basis for these effects is incompletely understood. Without clear engineering guidelines, attempts to use N-glycosylation as an approach for stabilizing proteins have resulted in unpredictable energetic consequences. Here, we review the recent development of three "enhanced aromatic sequons," which appear to facilitate stabilizing native-state interactions between Phe, Asn-GlcNAc and Thr when placed in an appropriate reverse turn context. It has proven to be straightforward to engineer a stabilizing enhanced aromatic sequon into glycosylation-naive proteins that have not evolved to optimize specific protein-carbohydrate interactions. Incorporating these enhanced aromatic sequons into appropriate reverse turn types within proteins should enhance the well-known pharmacokinetic benefits of N glycosylation-based stabilization by lowering the population of protease susceptible unfolded and aggregation-prone misfolded states, thereby making such proteins more useful in research and pharmaceutical applications. PMID- 22782564 TI - Structure and transmembrane topology of Slc11a1 TMD1-5 in lipid membranes. AB - The importance of solute carrier family 11 (Slc11) in divalent metal-ion transport has been well established. The core domains TMD1-5 and TMD6-10 of the proteins were modeled as a symmetric but inversely orientated arrangement with respect to membrane normal. In this article, the structures and transmembrane topologies of TMD1-5 of Slc11a1 incorporated with phospholipids 1-palmitoyl-2 oleoyl- sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3 [phospho-rac-(1-glycerol)] (sodium salt) (POPG), and POPC/POPG (3:1) were explored using circular dichroism, fluorescence, and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopies. The segments TMD2-5 were inserted in lipid membranes mainly as an alpha-helix with orientations of helices along membrane normal. The tilt angles of the helices were in an order of TMD3 > TMD4 > TMD2 > TMD5 in these membranes. In contrast, TMD1 was partly inserted in membranes, leaving partial segment at membrane surface. The amount of the lipid component with negatively charged headgroups had an effect on both the helicity and orientation of the transmembrane domains (TMDs). Nevertheless, the helices maintained similar topologies in various membranes. PMID- 22782563 TI - Dissecting a role of evolutionary-conserved but noncritical disulfide bridges in cysteine-rich peptides using omega-conotoxin GVIA and its selenocysteine analogs. AB - Conotoxins comprise a large group of peptidic neurotoxins that use diverse disulfide-rich scaffolds. Each scaffold is determined by an evolutionarily conserved pattern of cysteine residues. Although many structure-activity relationship studies confirm the functional and structural importance of disulfide crosslinks, there is growing evidence that not all disulfide bridges are critical in maintaining activities of conotoxins. To answer the fundamental biological question of what the role of noncritical disulfide bridges is, we investigated function and folding of disulfide-depleted analogs of omega conotoxin GVIA (GVIA) that belongs to an inhibitory cystine knot motif family and blocks N-type calcium channels. Removal of a noncritical Cys1-Cys16 disulfide bridge in GVIA or its selenopeptide analog had, as predicted, rather minimal effects on the inhibitory activity on calcium channels, as well as on in vivo activity following intracranial administration. However, the disulfide-depleted GVIA exhibited significantly lower folding yields for forming the remaining two native disulfide bridges. The disulfide-depleted selenoconotoxin GVIA analog also folded with significantly lower yields, suggesting that the functionally noncritical disulfide pair plays an important cooperative role in forming the native disulfide scaffold. Taken together, our results suggest that distinct disulfide bridges may be evolutionarily preserved by the oxidative folding or/and stabilization of the bioactive conformation of a disulfide-rich scaffold. PMID- 22782565 TI - Improvement of probe peptides for coiled-coil labeling by introducing phosphoserines. AB - We have developed a method of rapidly labeling membrane proteins in living cells using a high-affinity heterodimeric coiled-coil construct containing an E3 tag (EIAALEK)(3) genetically fused to the target protein and a K4 probe (KIAALKE)(4) labeled with a fluorophore such as tetramethylrhodamine (TMR) at its N-terminus (TMR-K4). However, coiled-coil labeling cannot be applied to highly negatively charged cell lines such as HEK293, because of the nonspecific adsorption of the positively charged K4 probes to cell membranes. To reduce the net positive charge, we synthesized new probes that include phosphoserine residues (pSer) between the K4 sequence and TMR fluorophore (TMR-(pSer)(n)-K4, [n = 1-3]). The affinity of the pSer-introduced probes was comparable to that of the TMR-K4 probe. However, the TMR-(pSer)(2)-K4 and TMR-(pSer)(3)-K4 probes tended to aggregate during labeling. In contrast, TMR-pSer-K4, which was as soluble as TMR K4, achieved higher signal/background ratios (30-100) for four host cell lines (HEK293, HeLa, SH-SY5Y, and PC12) than did TMR-K4 (~10 for HEK293 cells), demonstrating that the improved probe can be used for various types of cells. PMID- 22782566 TI - Synthesis, characterization, and evaluation of PS-PPDC resin: a novel flexible cross-linked polymeric support for solid-phase organic synthesis. AB - The present study describes the synthesis of different mole densities of poly(propylene glycol)dimethacrylate cross-linked resins using monomer units such as styrene and 4-chloromethyl styrene and its evaluation as an ideal support toward different stages of solid-phase peptide synthesis. Free radical generated aqueous suspension polymerization has been followed for polymerization and the formation of resin was characterized using infrared and carbon-13 spectroscopic techniques. Surface morphology of resin was examined by scanning electron microscopy. The polymerization reaction was investigated with respect to the effect of amount of cross-linking agent to verify the swelling, loading, and the mechanical stability of resin. Solvent imbibition abilities in commonly used solvents were measured and compared to commercially available Merrifield as well as reported styrene-acryloyloxyhydroxypropyl methacrylate-tripropyleneglycol diacrylate (SAT resins. The chemical inertness of the support was also checked with different reagents used for solid-phase peptide synthesis. The suitability of support was demonstrated by synthesizing biologically potent Endothelin class of linear peptides by Fmoc strategy and compared to SAT resin. The purities of synthetic peptides were analyzed by high-performance liquid chromatography and corresponding masses by matrix-assisted laser desorption/ionisation-time of flight analysis. PMID- 22782567 TI - Society members contributing to the journal. PMID- 22782568 TI - Detection of coronary plaques using MR coronary vessel wall imaging: validation of findings with intravascular ultrasound. AB - OBJECTIVES: Compared with X-ray coronary angiography (CAG), magnetic resonance imaging of the coronary vessel wall (MR-CVW) may provide more information about plaque burden and coronary remodelling. We compared MR-CVW with intravascular ultrasound (IVUS), the standard of reference for coronary vessel wall imaging, with regard to plaque detection and wall thickness measurements. METHODS: In this study 17 patients with chest pain, who had been referred for CAG, were included. Patients underwent IVUS and MR-CVW imaging of the right coronary artery (RCA). Subsequently, the coronary vessel wall was analysed for the presence and location of coronary plaques. RESULTS: Fifty-two matching RCA regions of interest were available for comparison. There was good agreement between IVUS and MR-CVW for qualitative assessment of presence of disease, with a sensitivity of 94% and specificity of 76%. Wall thickness measurements demonstrated a significant difference between mean wall thickness on IVUS and MR-CVW (0.48 vs 1.24 mm, P < 0.001), but great heterogeneity between wall thickness measurements, resulting in a low correlation between IVUS and MR-CVW. CONCLUSIONS: MR-CVW has high sensitivity for the detection of coronary vessel wall thickening in the RCA compared with IVUS. However, the use of MRI for accurate absolute wall thickness measurements is not supported when a longitudinal acquisition orientation is used. PMID- 22782570 TI - On the nature of mental disorder: towards an objectivist account. AB - According to the predominant view within contemporary philosophy of psychiatry, mental disorders involve essentially personal and societal values, and thus, the concept of mental disorder cannot, even in principle, be elucidated in a thoroughly objective manner. Several arguments have been adduced in support of this impossibility thesis. My critical examination of two master arguments advanced to this effect by Derek Bolton and Jerome Wakefield, respectively, raises serious doubts about their soundness. Furthermore, I articulate an alternative, thoroughly objective, though in part normative, framework for the elucidation of the concept of mental disorder. The concepts of mental dysfunction and impairment of basic psychological capacities to satisfy one's basic needs are the building blocks of this framework. I provide an argument for the objective harmfulness of genuine mental disorders as patterns of mental dysfunctions with objectively negative biotic values, as well as a formally correct definition of the concept of mental disorder. Contrary to the received view, this objective framework allows for the possibility of genuine mental disorders due to adverse social conditions, as well as for quasi-universal mental disorders. I conclude that overall, the project of providing an objective account of the concept of mental disorder is far from impossible, and moreover, that it is, at least in principle, feasible. PMID- 22782572 TI - Changing landscapes in cellular oncology. PMID- 22782569 TI - Frequency and predictors of endoleaks and long-term patency after covered stent placement for the treatment of intracranial aneurysms: a prospective, non randomised multicentre experience. AB - OBJECTIVE: We investigated immediate/late endoleaks and long-term patency following stent-graft placement for treatment of intracranial aneurysms located within the distal internal carotid artery (ICA) or vertebral artery (VA). METHODS: Forty-five aneurysms in 41 patients receiving covered stents in three centres were followed. Outcome measures included aneurysm occlusion rate, endoleaks, late in-stent stenosis rate, clinical improvement, neurological deficiencies and death. RESULTS: Total aneurysm exclusion was achieved in 69.2% (n = 27), with 30.8% (n = 12) experiencing immediate residual endoleaks. Angiographic follow-up (mean 43.5 +/- 14.3 months) revealed that 87.2% (n = 34) were completely occluded with only 12.8% (n = 5) showing residual endoleaks. Predictors of immediate endoleaks in our patient group were stent number (P = 0.023) and stent diameter (P = 0.022), while predictors of late endoleaks in our patient group were stent diameter (P = 0.035) and stent angulation (P = 0.021). Late in-stent stenosis rates were 18.0 +/- 13.3 and 29.0 +/- 18.5% compared with the period immediately following implantation at 2- and 6-year follow-ups respectively. Smoking (P = 0.017) and stent angulation (P = 0.020) were predictors of late in-stent stenosis. CONCLUSION: Treating intracranial aneurysms with Willis stent-grafts has an acceptable immediate and late occlusion rate and long-term stented artery patency rate. PMID- 22782571 TI - Shaken but unstirred? Effects of micronutrients on stress and trauma after an earthquake: RCT evidence comparing formulas and doses. AB - OBJECTIVE: To compare two micronutrient (vitamins and minerals) formulas (BeroccaTM and CNETM) and assess their impact on emotions and stress related to the 6.3 earthquake on February 22(nd) 2011 in Christchurch, New Zealand. METHODS: 91 adults experiencing heightened anxiety or stress 2-3 months following the earthquake were randomized to BeroccaTM, CNETM low dose (CNE4), or CNETM high dose (CNE8), for 28 days and monitored weekly via on-line questionnaires and followed 1 month post-trial. A nonrandomized control group (n = 25) completed questionnaires at baseline and 4 weeks. RESULTS: All treatment groups experienced significant declines in psychological symptoms (p < .001). CNETM groups experienced greater reduction in intrusive thoughts as compared with BeroccaTM (p = .05), with no group differences on other measures of psychological symptoms. However, CNE8 group reported greater improvement in mood, anxiety, and energy (p < .05) with twice as many reporting being "much" to "very much" improved and five times more likely to continue taking CNETM post-trial than BeroccaTM group. Treated participants had better outcomes on most measures over 4 weeks as compared to controls. CONCLUSIONS: This study supports micronutrients as an inexpensive and practical treatment for acute stress following a natural disaster with a slight advantage to higher doses ACTRN 12611000460909. PMID- 22782573 TI - Voriconazole is delivered from antifungal-loaded bone cement. AB - BACKGROUND: Local delivery of antifungals is an important modality in managing orthopaedic fungal infection. Voriconazole is a powder antifungal suitable for addition to bone cement that is released from bone cement but the mechanical properties of antimicrobial-loaded bone cement (ALBC) made with voriconazole are unknown. QUESTIONS/PURPOSES: (1) Is voriconazole release dose-dependent? (2) Is released voriconazole active? (3) Is the loss of ALBC's compressive strength caused by voriconazole dose- and elution-dependent? METHODS: Sixty standard test cylinders were fabricated with ALBC: 300 or 600 mg voriconazole per batch eluted for 30 days in deionized water. Voriconizole concentration in the eluate was measured using high-performance liquid chromatography. Cumulative-released voriconizole was calculated. Biologic activity was tested. Compressive strength was measured before and after elution. The effect of dose and time on release and compressive strength were analyzed using repeated-measure analysis of variance. RESULTS: Fifty-seven percent and 63% of the loaded voriconazole were released by Day 30 for the 300-mg and 600-mg formulations, respectively. The released voriconazole was active on bioassay. Compressive strength was reduced from 79 MPa to 53 MPa and 69 MPa to 31 MPa by 30 days for the 300-mg and 600-mg formulations, respectively. CONCLUSIONS: Voriconazole release from ALBC increases with dose and is bioactive. Loss in compressive strength is greater after elution and with higher dose. CLINICAL RELEVANCE: Three hundred milligrams of voriconazole in ALBC would be expected to deliver meaningful amounts of active drug in vivo. The compressive strength of ALBC with 600 mg voriconazole is less than expected compared to commonly used antibacterials. PMID- 22782574 TI - Synthesis of spin-crossover nano- and micro-objects in homogeneous media. AB - New methods are proposed for the synthesis of spin-crossover nano- and micro objects. Several nano-objects that are based upon the spin-crossover complex [Fe(hptrz)(3)](OTs)(2) (hptrz=4-heptyl-1,2,4-triazole, Ts=para-toluenesulfonyl) were prepared in homogeneous media. The use of various reagents (Triton X-100, PVP, TOPO, and PEGs of different molecular weights) as stabilizing agents yielded materials of different size (6 nm-2 MUm) and morphology (nanorods, nanoplates, small spherical particles, and nano- and micro-crystals). In particular, when Triton X-100 was used, a variation in the morphology from nanorods to nanoplates was observed by changing the nature of the solvent. Interestingly, the preparation of the nanorods and nanoplates was always accompanied by the formation of small spherical particles. Alternatively, when PEG was used, 200-400 nm crystals of the complex were obtained. In addition, a very promising polymer free synthetic method is discussed that was based on the preparation of relatively stable Fe(II)-triazole oligomers in CHCl(3). Their specific treatment led to micro-crystals, small nanoparticles, or gels. The size and morphology of all of these objects were characterized by TEM and by dynamic light scattering (DLS) where possible. Their spin-crossover behavior was studied by optical and magnetic measurements. The spin-transition features for large particles (>100 nm) were very similar to that of the bulk material, that is, close to room temperature with a hysteresis width of up to 8 K. The effects of the matrix and/or size-reduction led to modification of the transition temperature and an abruptness of the spin transition for oligomeric solutions and small nanoparticles of 6 nm in size. PMID- 22782576 TI - Membrane lateral structure: the influence of immobilized particles on domain size. AB - In experiments on model membranes, formation of large domains of different lipid composition is readily observed. However, no such phase separation is observed in the membranes of intact cells. Instead, small transient inhomogeneities called lipid rafts are expected in these systems. One of the numerous attempts to explain small domains refers to the coupling of the membrane to its surroundings, which leads to the immobilization of some of the membrane molecules. These immobilized molecules then act as static obstacles for the remaining mobile ones. We present detailed Molecular Dynamics simulations demonstrating that this can indeed account for small domains. This confirms previous Monte Carlo studies based on simplified models. Furthermore, by directly comparing domain structures obtained using Molecular Dynamics to Monte Carlo simulations of the Ising model, we demonstrate that domain formation in the presence of obstacles is remarkably insensitive to the details of the molecular interactions. PMID- 22782575 TI - ADAMTS13 exerts a thrombolytic effect in microcirculation. AB - Recombinant tissue plasminogen activator (r-tPA) is the drug of choice for thrombolysis, but it is associated with a significant risk of bleeding and is not always successful. By cleaving von Willebrand factor (VWF), the metalloprotease ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) down-regulates thrombus formation in injured vessels. We investigated whether recombinant ADAMTS13 (r-ADAMTS13) induces thrombolysis in vivo in mice. Thrombosis was produced by ferric chloride-induced (FeCl(3)) injury in the venules of a dorsal skinfold chamber. Phosphate-buffered saline (PBS, vehicle), r tPA or r-ADAMTS13, supplemented with hirudin (to stop on-going thrombin generation), was directly applied onto the occluded vessel, and thrombus dissolution was evaluated by intravital microscopy. The incidence of blood flow restoration significantly increased 30 minutes (min) after r-ADAMTS13 vs. PBS treatment (60% vs. 0%, p<0.05) and 60 min after r-tPA treatment (75% vs. 17%, p<0.05). Both r-tPA and r-ADAMTS13 significantly reduced thrombus size 60 min after their superfusion (53.2% and 62.3% of the initial thrombus size, p<0.05 and p<0.01, respectively). Bleeding occurred in all r-tPA-treated chambers, while it was absent in mice treated with r-ADAMTS13 or PBS. We observed that, similar to r tPA, r-ADAMTS13 can dissolve occlusive thrombi induced by FeCl(3) injury in venules. In contrast to r-tPA, the in vivo thrombolytic effect of ADAMTS13 was not associated with any signs of haemorrhage. ADAMTS13 could represent a new therapeutic option for thrombolysis. PMID- 22782577 TI - Is radiological evaluation as good as computer-based volumetry to assess hippocampal atrophy in Alzheimer's disease? AB - INTRODUCTION: Hippocampus volumetry is a useful surrogate marker for the diagnosis of Alzheimer's disease (AD). Our purpose was to compare visual assessment of medial temporal lobe atrophy made by radiologists with automatic hippocampal volume and to compare their performances for the classification of AD, mild cognitive impairment (MCI) and cognitively normal (CN). METHODS: We studied 30 CN, 30 MCI and 30 AD subjects. Six radiologists with two levels of expertise performed two readings of medial temporal lobe atrophy. Medial temporal lobe atrophy was evaluated on coronal three-dimensional T1-weighted images using Scheltens scale and compared with hippocampal volume obtained using a fully automatic segmentation method (Spearman's rank coefficient). RESULTS: Visual assessment of medial temporal lobe atrophy was correlated with hippocampal volume (p < 0.01). Classification performances between MCI converter and CN was better using volumetry than visual assessment of non-expert readers whereas classification of AD and CN did not differ between visual assessment and volumetry except for the first reading of one non-expert (p = 0.03). CONCLUSIONS: Visual assessment of medial temporal lobe atrophy by radiologists was well correlated with hippocampal volume. Radiological assessment is as good as computer-based volumetry for the classification of AD, MCI non-converter and CN and less good for the classification of MCI converter versus CN. Use of Scheltens scale for assessing hippocampal atrophy in AD seems thus justified in clinical routine. PMID- 22782579 TI - Milk yield persistency in Brazilian Gyr cattle based on a random regression model. AB - With the objective of evaluating measures of milk yield persistency, 27,000 test day milk yield records from 3362 first lactations of Brazilian Gyr cows that calved between 1990 and 2007 were analyzed with a random regression model. Random, additive genetic and permanent environmental effects were modeled using Legendre polynomials of order 4 and 5, respectively. Residual variance was modeled using five classes. The average lactation curve was modeled using a fourth-order Legendre polynomial. Heritability estimates for measures of persistency ranged from 0.10 to 0.25. Genetic correlations between measures of persistency and 305-day milk yield (Y305) ranged from -0.52 to 0.03. At high selection intensities for persistency measures and Y305, few animals were selected in common. As the selection intensity for the two traits decreased, a higher percentage of animals were selected in common. The average predicted breeding values for Y305 according to year of birth of the cows had a substantial annual genetic gain. In contrast, no improvement in the average persistency breeding value was observed. We conclude that selection for total milk yield during lactation does not identify bulls or cows that are genetically superior in terms of milk yield persistency. A measure of persistency represented by the sum of deviations of estimated breeding value for days 31 to 280 in relation to estimated breeding value for day 30 should be preferred in genetic evaluations of this trait in the Gyr breed, since this measure showed a medium heritability and a genetic correlation with 305-day milk yield close to zero. In addition, this measure is more adequate at the time of peak lactation, which occurs between days 25 and 30 after calving in this breed. PMID- 22782578 TI - New developments in steroid-resistant nephrotic syndrome. AB - Nephrotic syndrome is a disorder of the glomerular filtration barrier, a highly specialised tri-layer structure with unique functional properties. Recent advances emanating from the field of molecular genetics have revealed the podocyte as probably the central player in the control of glomerular filtration. More specifically, the cell-cell junction between adjacent podocyte foot processes, namely, the slit diaphragm, has been revealed to be made up of a sophisticated multi-protein complex which dynamically controls foot process architecture via signalling to the actin cytoskeleton. Key genes that have been identified from the study of inherited nephrotic syndromes include those encoding nephrin, podocin, TRPC6 (transient receptor potential canonical channel-6) and alpha-actinin-4, and more remain to be found. It is now possible to identify genetic causes underlying a proportion of nephrotic syndromes presenting at any age. The next big challenge for clinicians and researchers is to translate the molecular information learnt into the understanding of acquired, non-inherited forms of the disease and to guide therapeutic options. In this regard several exciting advances have been made, both in understanding the molecular mechanisms of current therapies and in revealing circulating plasma factors and the molecular pathways they trigger in the podocyte, that could be targeted by novel therapies. PMID- 22782580 TI - Lack of association of CYP1A1-MspI SNP and GSTM1 null genotypes with cancer in a Brazilian family with unusually high cancer incidence. AB - Research has shown that genetic polymorphisms in biotransformation enzymes, such as CYP1A1 and GSTM1, are related to a greater or lesser susceptibility to various cancers. We made an analysis of CYP1A1m1 SNP and GSTM1 null genotypes in a family group (71 members) related by consanguinity who had an unusually high incidence of cancer and a high frequency of smokers. There were no significant differences in genotype frequencies in this family when compared to data for Brazilian populations. Possibly, the high incidence of cancer in this sample is associated with smoking and/or other factors not detected in this survey. PMID- 22782581 TI - Geographic shifts in climatically suitable areas and loss of genetic variability in Dipteryx alata ("Baru" Tree; Fabaceae). AB - Many species are expected to suffer strong shifts in their geographic ranges due to climate changes in the next 50 years, with severe consequences for biodiversity patterns and population structure. We used here an ensemble forecast approach for obtaining species' range in which multiple species distribution models and climatic models were combined to model loss of genetic variability in Baru, Dipteryx alata (Fabaceae), an economically important Neotropical tree native to the Cerrado of Brazil. We estimated a series of genetic parameters (number of alleles per locus, expected heterozygosity under Hardy-Weinberg equilibrium and mutation-drift equilibrium) for this species based on eight microsatellite loci. We then recalculated these parameters assuming that local populations in areas of low future environmental suitability will go extinct. All genetic parameters remained approximately constant up to a 50% threshold of climatic suitability in the future; after this critical threshold there is an abrupt reduction in all parameters, although the magnitude of shift is only about 10% of current values, on average. Thus, despite the shifts in geographic range and climatically suitable areas towards southeastern Brazil, our analyses do not predict a strong loss of genetic diversity in D. alata because of the broad tolerance of this species, which ensures large future ranges, contrasting with other Cerrado species that have been analyzed in a similar manner. PMID- 22782582 TI - Analysis of Antarctic proteobacteria by PCR fingerprinting and screening for antimicrobial secondary metabolites. AB - Fifty-seven proteobacterium species were successfully isolated from soils of Barrientos Island of the Antarctic using 11 different isolation media. Analysis of 16S rDNA sequencing of these isolates showed that they belonged to eight different genera, namely Bradyrhizobium, Sphingomonas, Methylobacterium, Caulobacter, Paracoccus, Ralstonia, Rhizobium, and Staphylococcus. All isolates were studied for capability of producing antimicrobial and antifungal secondary metabolites using high-throughput screening models. Approximately 23 (13/57) and 2% (1/57) of isolates inhibited growth of Candida albicans ATCC 10231(T) and Staphylococcus aureus ATCC 51650(T), respectively. These results indicated that proteobacterium species isolates from Antarctic could serve as potential source of useful bioactive metabolites. Enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprinting produced nine clusters and 13 single isolates, with a high D value of 0.9248. RAPD fingerprinting produced six clusters and 13 single isolates, with a relatively low D value of 0.7776. ERIC-PCR analysis proved to have better discrimination capability than RAPD analysis and generated better clustering for all proteobacterium species isolates. We conclude that ERIC-PCR is a robust, reliable and rapid molecular typing method for discriminating different genera of proteobacteria. PMID- 22782583 TI - Meta-analysis of epidemiological studies demonstrates significant association of PTGS2 polymorphism rs689470 and no significant association of rs20417 with prostate cancer. AB - Evidence is accumulating that chronic inflammation has an important role in prostate cancer. Two common polymorphisms in the prostaglandin-endoperoxide synthase 2 (PTGS2) gene, rs20417 and rs689470, have been found to alter the risk for prostate cancer, but the various studies are not in agreement. To derive a more precise estimation of this association, all available studies were considered in a meta-analysis, with 10,700 patients and 13,021 controls for rs20417 and 4087 patients and 3761 controls for rs689470. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) to determine the precision of the estimate. When all groups were pooled, we did not detect a significant association of rs20417 polymorphism with prostate cancer risk. Similarly, no associations were found in the subgroup analysis. However, we found that rs689470 was significantly associated with a trend towards increased prostate cancer risk when using both additive (OR = 2.15, 95%CI = 1.04-4.44, P = 0.04) and recessive models (OR = 2.07, 95%CI = 1.07-4.03, P = 0.03) to analyze the data. In subgroup analyses stratified by ethnicity, there was no evidence that rs689470 has a significant association with prostate cancer in Caucasians. Based on our meta-analysis, rs689470 polymorphism is significantly associated with prostate cancer risk in the overall population. Nevertheless, we suggest that further studies should be made to confirm these findings. PMID- 22782584 TI - Cloning, expression analysis and sequence prediction of the CCAAT/enhancer binding protein alpha gene of Qinchuan cattle. AB - CCAAT/enhancer-binding protein alpha (C/EBPalpha) is an essential transcription factor, regulating the differentiation of adipocytes. We cloned the complete open reading frame of C/EBPalpha gene of Qinchuan cattle and analyzed its protein structures and expression profile in 15 tissues via DNA cloning, sequencing and RT-PCR. Analysis of the putative protein sequences revealed that C/EBPalpha consists of alpha helices, random coils and a few extended strands. A significant transmembrane structure was observed in amino acid region 233 to 252. A basic leucine zipper domain was also found in amino acid region 277 to 340, which is characteristic of C/EBPs. Homologous comparison with various species indicated that the C/EBPalpha gene of Qinchuan cattle shares 97, 95, 94, 94, and 93% similarity in amino acid sequences with Sus scrofa, Homo sapiens, Rattus norvegicus, Oryctolagus cuniculus, and Mus musculus, respectively, implying strong sequence conservation of C/EBPalpha during evolution. RT-PCR revealed that the mRNA expression level of bovine C/EBPalpha gene in subcutaneous fat is much higher than that in the other 14 tissues, and the relative quantity in fat tissue increases with cattle age. PMID- 22782585 TI - Isolation and characterization of microsatellite DNA loci from the peanut worm, Sipunculus nudus. AB - Sipunculus nudus, the peanut worm, is the best known species in its genus. This unsegmented subtidal marine worm is consumed in some parts of Asia and is also used as fish bait. We found 20 microsatellite DNA markers for S. nudus. The number of alleles per polymorphic locus ranged from two to seven in a sample of 39 individuals. Observed and expected heterozygosities per polymorphic locus varied from 0.103 to 1.000 and from 0.307 to 0.771, respectively. Five loci showed significant departure from Hardy-Weinberg equilibrium after sequential Bonferroni's correction. No significant linkage disequilibrium between pairs of loci was found. These microsatellite markers will provide useful tools for investigating genetic population structure, population history and conservation management of S. nudus. PMID- 22782586 TI - New cytogenetic aberrations found in a case of aggressive retinoblastoma. AB - We describe a case of retinoblastoma with an atypical presentation and previously unreported cytogenetic aberrations. A 19-month-old girl with left intraocular retinoblastoma was treated with enucleation and chemotherapy. The disease showed aggressive evolution within a short period between diagnosis and relapse. Eight months after diagnosis, a new large tumor was present in the orbit of the right eye, with diffuse bone pain, pancytopenia and diffuse infiltration into the bone marrow and the central nervous system. The child did not respond to treatment and died. Cytogenetic studies made with G-banding, FISH and SKY analysis showed chromosomal aberrations commonly associated with retinoblastoma, including del(13q), i(6p), +1, and monosomy 16, along with others that had not been reported previously, including dup(5q), dic(15;22) and add(14q). The new chromosomal aberrations may be related to the aggressiveness of the disease in this case. PMID- 22782587 TI - Ovine prion protein genotype frequencies in northwestern China. AB - Anti-scrapie breeding programs have been initiated to screen for scrapie resistant sheep based on ovine prion protein gene (PRNP) genotypes at codons 136, 154 and 171 in many countries, especially European Union member states. However, investigation of sheep PRNP genotypes is limited in China, despite the large number of sheep breeds. We analyzed 432 sheep of five different breeds from farms in northwestern China, using PCR-single-strand conformational polymorphism analysis (PCR-SSCP); the corresponding haplotypes of different PRNP alleles were cloned. PRNP allele genotyping was done by amplification refractory mutation system-PCR (ARMS-PCR), according to the haplotype clones of each PRNP allele. The validity of ARMS-PCR was checked by PCR-SSCP. Another 325 unknown PRNP genotypes of other sheep breeds were analyzed according to the established ARMS-PCR. Genotype frequencies of 757 sheep were analyzed with these two methods to evaluate susceptibility to scrapie in northwestern China. Relevant mutations were also detected at other sites. Both methods were effective for ovine PRNP allele genotyping, and the results of the analysis completely coincided. Scrapie resistant genotypes were found to be uncommon, indicating a high risk for ovine scrapie in northwest China. In addition to codons 136, 154 and 171, we found numerous new mutations; nearly half of them were previously unreported. These sheep populations have a high degree of polymorphism at the PRNP locus. PMID- 22782588 TI - Screening and identification of peritoneal metastasis-related genes of gastric adenocarcinoma using a cDNA microarray. AB - With the aim of identifying peritoneal metastasis-related genes in gastric cancer, we performed a broad analysis of differential gene expression between the parental cell line GC9811 and its highly metastatic peritoneal counterpart, cell line GC9811-P. Two fluorescent cDNA probes, labeled with Cy3 and Cy5 dyes, were prepared from GC9811 and GC9811-P mRNA samples by the reverse transcription method. The two color probes were then mixed and hybridized to a cDNA chip constructed with double-dots from 11,901 human genes; this was scanned at two wavelengths. The experiment was repeated twice. In GC9811-P cells, 218 genes were upregulated and 30 genes were downregulated compared with the parental cell lines. Some selected genes were confirmed by RT-PCR and Western blot; we found that S100A4 and CTNNB1 were upregulated and PTEN was downregulated in GC9811-P cells. Identification of these differentially expressed genes could contribute to disclose the molecular mechanisms involved and provide new targets for therapeutic intervention to avoid peritoneal dissemination of gastric adenocarcinoma. PMID- 22782589 TI - Genome-wide analysis of immunophilin FKBP genes and expression patterns in Zea mays. AB - The receptors for the immunosuppression drugs FK506 and rapamycin are called FKBPs (FK506-binding proteins). FKBPs comprise a large family; they are found in many species, including bacteria, fungi, animals, and plants. As a class of peptidyl-prolyl cis-trans isomerase enzymes, the FKBP genes have been the focus of recent studies on plant stress tolerance and immunology. We identified and analyzed gene families encoding these proteins in maize using computational and molecular biology approaches. Thirty genes were found to encode putative FKBPs according to their FK506-binding domain. The FKBP genes can be classified into single domain and multiple domain members based on the number of the domains. By analysis of the physical locations, the 30 FKBP genes were found to be widely distributed on 10 chromosomes. After analysis of the FKBP phylogenetic tree in the maize genome, we found that the 30 genes revealed two major clades. Gene duplication played a major role in the evolution of FKBP genes, which suggests that the FKBP genes in maize have a pattern significantly different from that of these genes in rice. Based on semi-quantitative RT-PCR, we found that the 30 FKBPs were expressed differently in various tissues in maize, which suggests that FKBP genes play different roles in each tissue. Several FKBPs were expressed at higher levels in roots, indicating that these genes in maize may have similar or overlapping functions. PMID- 22782590 TI - Microsystems for biomimetic stimulation of cardiac cells. AB - The heart is a complex integrated system that leverages mechanoelectrical signals to synchronize cardiomyocyte contraction and push blood throughout the body. The correct magnitude, timing, and distribution of these signals is critical for proper functioning of the heart; aberrant signals can lead to acute incidents, long-term pathologies, and even death. Due to the heart's limited regenerative capacity and the wide variety of pathologies, heart disease is often studied in vitro. However, it is difficult to accurately replicate the cardiac environment outside of the body. Studying the biophysiology of the heart in vitro typically consists of studying single cells in a tightly controlled static environment or whole tissues in a complex dynamic environment. Micro-electromechanical systems (MEMS) allow us to bridge these two extremes by providing increasing complexity for cell culture without having to use a whole tissue. Here, we carefully describe the electromechanical environment of the heart and discuss MEMS specifically designed to replicate these stimulation modes. Strengths, limitations and future directions of various designs are discussed for a variety of applications. PMID- 22782591 TI - Soft tissue sarcoma and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome: formulation of an hypothesis. AB - Hereditary non-polyposis colorectal cancer (HNPCC) is a genetic disorder caused by mutation in one of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) which predisposes to colorectal cancer and other malignances, that not yet include sarcomas. For sustaining that soft tissue sarcomas could be HNPCC related malignances, we report on a HNPCC patient with leiomyosarcoma and review the English literature. Overall, we report on eleven cases of soft tissue malignant tumors involving HNPCC patients, with a mean age of 34 years at diagnosis of sarcomas. In the majority of these tumors loss of MSH2 expression can be found at immunohistochemistry (IHC) and in 10 patients a germline mutation in one of the MMR genes was found (7 cases were MSH2 defective and 3 cases MLH1 defective). Data for supporting our hypothesis are also experimental, epidemiologic, histopathological: excess of sarcomas in PMS2 defective mice; sporadic soft tissue sarcomas are rare, with mean age at onset of 56 years and normal IHC for MMR proteins. In conclusion, the data collected support the hypothesis that soft tissue sarcomas could be included in the spectrum of tumors that, even if rarely, depend on MMR genes deficiency. PMID- 22782592 TI - Molecular cloning, sequence characterization and heterologous expression of buffalo (Bubalus bubalis) oviduct-specific glycoprotein in E. coli. AB - Oviductin is a high molecular weight oviduct-specific glycoprotein secreted by the non-ciliated epithelial cells of oviduct during estrous cycle and early pregnancy. It plays an important role during fertilization and early embryonic development. The oviductin gene from oviductal tissues of buffalo was successfully cloned and sequenced. The sequence analysis revealed that buffalo and cattle oviductin share very high homology between their cDNA sequences. The predicted amino acid sequences of the buffalo oviductin exhibited the highest percent of identity of 97 % with bovine followed by 94 % with goat, 93 % with sheep, 78 % with porcine, 72 % with human, 67 % with hamster and rabbit and 65 % with mouse. Oviductin was also observed to share high similarity with the mammalian chitinase, however oviductins do not show chitinase activity due to Glu >Ile mutation in the active site responsible for chitinase activity. The phylogenetic tree based on amino acid sequences of oviductin indicated that buffalo oviductin was closely related to its cattle counterpart, and this clustering is in accordance with the classic taxonomic relationship. Tissue specific expression of the transcripts for buffalo oviductin revealed a high level expression in oviduct and ovary followed by testis, mammary gland, kidney, while in mammary epithelial cells and liver its expression was very low. The full length matured oviductin and its domains constituting chitinase-like domain and mucin-like domain were cloned into pET and pGEX series of expression vectors and over expressed in E. coli. The soluble recombinant oviductin was successfully purified to homogeneity. Full length recombinant oviductin was expressed partially in soluble form, where as the chitinase-like and mucin-like domains of oviductin were expressed in insoluble form and aggregating to form inclusion bodies at both 37 and 16 degrees C induction temperatures. PMID- 22782593 TI - Pancreatic thickness as a predictive factor for postoperative pancreatic fistula after distal pancreatectomy using an endopath stapler. AB - PURPOSE: No consistent risk factor has yet been established for the development of pancreatic fistula (PF) after distal pancreatectomy (DP) with a stapler. METHODS: A total of 31 consecutive patients underwent DP with an endopath stapler between June 2006 and December 2010 using a slow parenchymal flattening technique. The risk factors for PF after DP with an endopath stapler were identified based on univariate and multivariate analyses. RESULTS: Clinical PF developed in 7 of 31 (22 %) patients who underwent DP with a stapler. The pancreata were significantly thicker at the transection line in patients with PF (19.4 +/- 1.47 mm) in comparison to patients without PF (12.6 +/- 0.79 mm; p = 0.0003). A 16-mm cut-off for pancreatic thickness was established based on the receiver operating characteristic (ROC) curve; the area under the ROC curve was 0.875 (p = 0.0215). Pancreatic thickness (p = 0.0006) and blood transfusion (p = 0.028) were associated with postoperative PF in a univariate analysis. Pancreatic thickness was the only significant independent factor (odds ratio 9.99; p = 0.036) according to a multivariate analysis with a specificity of 72 %, and a sensitivity of 85 %. CONCLUSION: Pancreatic thickness is a significant independent risk factor for PF development after DP with an endopath stapler. The stapler technique is thus considered to be an appropriate modality in patients with a pancreatic thicknesses of <16 mm. PMID- 22782594 TI - Application of the HyperEye Medical System for esophageal cancer surgery: a preliminary report. AB - The HyperEye Medical System is a newly developed device that allows for the visualization of the fluorescent image of indocyanine green enhanced by near infrared light among the surrounding vivid color images. We recently applied this system to confirm the blood flow of an esophageal substitute, and for sentinel node navigation during esophagectomy. Five consecutive patients with thoracic esophageal cancer who underwent a subtotal esophagectomy between June 2010 and May 2011 were enrolled in the study. The esophageal substitute used for reconstruction was the stomach and ileocecum in four and one cases, respectively. In all cases with a reconstructive stomach, fine arterial blood flow and venous perfusion were observed. The blood flow of the reconstructive colon was poor before microvascular anastomosis, however, it dramatically increased after anastomosis. Concerning the sentinel node navigation, the fluorescence of lymph nodes, lymphatic vessels, and the tumor site were detected. The postoperative courses of all cases were uneventful, with no mortalities or anastomotic leakage occurring. PMID- 22782596 TI - Guidelines: what for? PMID- 22782595 TI - Heparin rescues sepsis-associated acute lung injury and lethality through the suppression of inflammatory responses. AB - Heparin, a potent blood anticoagulant, is known to possess anti-inflammatory activity. In this work, we investigated whether heparin can ameliorate acute lung injury and lethal response in lipopolysaccharide (LPS)-induced mouse model of sepsis. We found that heparin effectively rescued lethality, improved lung pathological changes, inhibited myeloperoxidase (MPO) activity, and reduced malondialdehyde (MDA) level, lung wet/dry weight ratio and Evans blue values in LPS-induced septic mice. In addition, heparin also inhibited the release of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6) and IL-1beta in serum and decreased the expression of p-p38, nuclear factor kappaB (NF-kappaB) and p-c-SRC kinase in lungs of septic mice. Our findings suggest that heparin is capable of suppressing the lethal response and acute lung injury associated with sepsis, and support the notion that heparin may be a potential therapeutic agent for the conditions associated with septic shock. PMID- 22782597 TI - Highlights of the Brazilian Thoracic Association guidelines for interstitial lung diseases. AB - Interstitial lung diseases (ILDs) are heterogeneous disorders, involving a large number of conditions, the approach to which continues to pose an enormous challenge for pulmonologists. The 2012 Brazilian Thoracic Association ILD Guidelines were established in order to provide Brazilian pulmonologists with an instrument that can facilitate the management of patients with ILDs, standardizing the criteria used for the diagnosis of different conditions and offering guidance on the best treatment in various situations. The objective of this article was to briefly describe the highlights of those guidelines. PMID- 22782598 TI - Exercise-induced bronchoconstriction in elite long-distance runners in Brazil. AB - OBJECTIVE: To determine the prevalence of exercise-induced bronchoconstriction among elite long-distance runners in Brazil and whether there is a difference in the training loads among athletes with and without exercise-induced bronchoconstriction. METHODS: This was a cross-sectional study involving elite long-distance runners with neither current asthma symptoms nor a diagnosis of exercise-induced bronchoconstriction. All of the participants underwent eucapnic voluntary hyperpnea challenge and maximal cardiopulmonary exercise tests, as well as completing questionnaires regarding asthma symptoms and physical activity, in order to monitor their weekly training load. RESULTS: Among the 86 male athletes recruited, participation in the study was agreed to by 20, of whom 5 (25%) were subsequently diagnosed with exercise-induced bronchoconstriction. There were no differences between the athletes with and without exercise-induced bronchoconstriction regarding anthropometric characteristics, peak oxygen consumption, baseline pulmonary function values, or reported asthma symptoms. The weekly training load was significantly lower among those with exercise-induced bronchoconstriction than among those without. CONCLUSIONS: In this sample of long distance runners in Brazil, the prevalence of exercise-induced bronchoconstriction was high. PMID- 22782599 TI - Comparison between two methods of asthma control evaluation based on individual perception. AB - OBJECTIVE: To compare the subjective perception of asthma control reported by the patient with that measured by the score obtained on the Asthma Control Questionnaire 6-item version (ACQ-6) in patients with severe asthma and to determine whether asthma control is associated with the number of emergency room visits in the previous month. METHODS: This was a cross-sectional study involving 528 patients treated at the Bahia State Asthma and Allergic Rhinitis Control Program Central Referral Clinic between August of 2008 and March of 2010, in the city of Salvador, Brazil. The patients completed the ACQ-6 and answered a specific additional question in order to evaluate their own perception of asthma control in the previous week. RESULTS: We evaluated 423 patients who met the inclusion criteria. The sample was predominantly female (81.3%), and 64.3% had an income lower than two times the national minimum wage. The mean age was 49.85 +/- 13.71 years, and the duration of asthma symptoms was 32.11 +/- 16.35 years. The patients had been regularly treated via the program for 36.65 +/- 18.10 months. Based on the subjective perception of asthma control, only 8% of the patients considered their asthma to be uncontrolled, whereas 38.8% had an ACQ-6 score > 1.5, which indicates poor control. The kappa statistic revealed poor concordance between the two methods. There was a direct association between uncontrolled asthma and the number of emergency room visits in the previous month (p < 0.001). CONCLUSIONS: In this sample of patients, the subjective perception of asthma control differed from that measured by the ACQ-6 score, and the patients overestimated their own level of asthma control, which puts them at risk of being undertreated. PMID- 22782600 TI - Respiratory muscle strength in children and adolescents with asthma: similar to that of healthy subjects? AB - OBJECTIVE: To compare children/adolescents with mild or moderate asthma and healthy subjects in terms of respiratory muscle strength, correlating it with spirometric variables in the former group. METHODS: This was a cross-sectional study involving individuals 6-16 years of age and clinically diagnosed with mild/moderate asthma, together with a group of healthy, age- and gender-matched subjects. We determined spirometric values, as well as MIP and MEP, and we selected three reproducible measurements (variation < 10%). RESULTS: We evaluated 75 patients with asthma and 90 controls. The mean age was 10.0 +/- 2.6 years. There were no statistically significant differences between the controls and the asthma group regarding MIP (-89.7 +/- 26.7 cmH2O vs. -92.2 +/- 26.3 cmH2O; p = 0.541) or MEP (79.2 +/- 22.9 cmH2O vs. 86.4 +/- 24.0 cmH2O; p = 0.256). The groups were subdivided by age (children and adolescents: 6-12 and 13-16 years of age, respectively). Within the asthma group, there was a significant difference between the child and adolescent subgroups in terms of MEP (74.1 +/- 24.1 cmH2O vs. 92.1 +/- 21.9 cmH2O; p < 0.001) but not MIP (p = 0.285). Within the control group, there were significant differences between the child and adolescent subgroups in terms of MIP (-79.1 +/- 17.7 cmH2O vs. -100.9 +/- 28.1 cmH2O; p < 0.001) and MEP (73.9 +/- 18.7 cmH2O vs. 90.9 +/- 28.1cmH2O; p < 0.001). In the asthma group, spirometric variables did not correlate with MIP or MEP. CONCLUSIONS: In our sample, asthma was found to have no significant effect on respiratory muscle strength. PMID- 22782601 TI - Flexible bronchoscopy as the first-choice method of removing foreign bodies from the airways of adults. AB - OBJECTIVE: To determine the success rate of flexible bronchoscopy as the first choice method of removing foreign bodies from the airways of adults. METHODS: This was a retrospective study of all adult patients (over 18 years of age) with foreign body aspiration submitted to bronchoscopy between January of 2009 and January of 2011 at the University of Sao Paulo School of Medicine Hospital das Clinicas, located in Sao Paulo, Brazil. RESULTS: The study sample comprised 40 adult patients, with a mean age of 52 years (range, 18-88 years). The median time of permanence of the foreign body in the airway was 15 days (range, 12 h to 10 years). All of the patients first underwent diagnostic flexible bronchoscopy. Foreign bodies were successfully removed with flexible bronchoscopy in 33 (82.5%) of the patients. In 1 patient, a metal object lodged in the distal bronchial tree required the use of fluoroscopy. Six patients (15%) required rigid bronchoscopy due to tracheal foreign body-induced dyspnea, in 2, and because the foreign body was too large for the flexible forceps, in 4. Bronchoscopy failed in 1 patient, who therefore required surgical bronchotomy. CONCLUSIONS: Although rigid bronchoscopy is considered the gold standard for the removal of foreign bodies from the airways, our experience showed that flexible bronchoscopy can be safely and effectively used in the diagnosis and treatment of stable adult patients. PMID- 22782602 TI - Immunophenotyping and extracellular matrix remodeling in pulmonary and extrapulmonary sarcoidosis. AB - OBJECTIVE: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. METHODS: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. RESULTS: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = -0.90; p = 0.04). CONCLUSIONS: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes. PMID- 22782603 TI - Influence that sociodemographic variables, clinical characteristics, and level of dependence have on quality of life in COPD patients on long-term home oxygen therapy. AB - OBJECTIVE: To evaluate and correlate the quality of life (QoL) of COPD patients on long-term home oxygen therapy (LTOT) with their sociodemographic/clinical characteristics and level of dependence. METHODS: This was a cross-sectional analytical study involving COPD patients on LTOT followed at the Oxygen Therapy Outpatient Clinic of the Federal University of Sao Paulo Hospital Sao Paulo, in the city of Sao Paulo, Brazil. Sociodemographic, clinical, and biochemical data were collected. We assessed QoL and level of dependence using the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and the Katz index, respectively. Multiple linear regression models were constructed in order to determine the influence of these variables on QoL. RESULTS: We included 80 patients in the study. The mean age was 69.6 +/- 9.1 years, and 51.3% were female. The lowest SF-36 scores were for the physical functioning and role physical domains. All sociodemographic characteristics (except gender) were found to correlate significantly with the SF-36 domains mental health, vitality, role physical, and social functioning. We also found that body mass index, PaO2, post bronchodilator FEV1, hemoglobin, and Katz index correlated significantly with the physical functioning, mental health, role-physical, and bodily pain domains. In addition, oxygen flows were found to correlate negatively with the physical functioning, mental health, vitality, and role-emotional domains. CONCLUSIONS: Low scores for SF-36 domains, as well as the variables that negatively influence them, should be considered and analyzed during the development and implementation of strategies for improving the QoL of COPD patients on LTOT. PMID- 22782604 TI - Cultural adaptation and reproducibility of the Breathing Problems Questionnaire for use in patients with COPD in Brazil. AB - OBJECTIVE: To translate the Breathing Problems Questionnaire (BPQ) into Portuguese and adapt it to the Brazilian culture, as well as to evaluate its reproducibility in patients with COPD. METHODS: After the BPQ had been translated and adapted to the Brazilian culture, it was administered to a subgroup of 8 patients in order to identify their uncertainties and difficulties. The questionnaire was reviewed by an expert committee, and its final version was arrived at. A second translator back-translated the final version into English, which was sent to the original author in order to verify that the original meaning of the questionnaire had been maintained. After the approval of the original author, the final Portuguese-language version of the questionnaire was administered to 50 patients with COPD, in order to evaluate its reproducibility. RESULTS: The mean response time was 9.5 min. Of the 50 patients, 21 were female and 29 were male. The mean age was 65.8 +/- 7.5 years. Most of the patients were classified as having moderate COPD (29.16%) or severe COPD (52%). The intraclass correlation coefficient (ICC) for the total score was 0.94. The ICCs for the eleven BPQ domains and its two subscales were also above 0.70. Moderate correlations were found between the BPQ domains and subscales. CONCLUSIONS: The translation and cultural adaptation of the BPQ for use in Brazil was deemed appropriate, because the patients could easily understand and answer the questions. In addition, the Brazilian version of the BPQ questionnaire was found to be reliable, showing good reproducibility. PMID- 22782605 TI - Six-minute walk distance is not related to quality of life in patients with non cystic fibrosis bronchiectasis. AB - OBJECTIVE: To evaluate physical performance on the six-minute walk test (6MWT) in patients with non-cystic fibrosis bronchiectasis and to investigate its relationship with quality of life (QoL). To identify predictors of exercise performance, we also investigated whether six-minute walk distance (6MWD) is associated with clinical and spirometric findings. METHODS: This was a cross sectional study involving patients with non-cystic fibrosis bronchiectasis (age, > 18 years), with at least one respiratory symptom for > 2 years and an FEV1 < 70% of predicted. Patients underwent clinical evaluation, pulmonary function tests, the 6MWT, and QoL assessment with the Medical Outcomes Study 36-item Short Form Health Survey (SF-36). RESULTS: We included 70 patients (48 females). Mean age was 54.5 +/- 17.7 years, and mean FEV1 was 44.9 +/- 14.5% of predicted. The patients were divided into two groups: 6MWD-low (6MWD below the predicted lower limit; n = 23); and 6MWD-norm (normal 6MWD; n = 47). The following variables were significantly lower in the 6MWD-low group than in the 6MWD-norm group: age; age at diagnosis of bronchiectasis; proportion of former smokers; body mass index (BMI); FEV1% of predicted; and MEP% of predicted. There were no significant differences in the SF-36 scores between the groups. In the logistic regression model, lower age and lower BMI were significantly associated with lower 6MWD. CONCLUSIONS: In this sample, there was a high proportion of patients who presented a lower than expected 6MWD. Although 6MWD was not related to QoL, it was associated with age and BMI. PMID- 22782606 TI - Smoking and abdominal fat in blood donors. AB - OBJECTIVE: To assess the association between smoking and abdominal fat among male blood donors. METHODS: This was a cross-sectional study involving 1,235 adult male blood donors (age, 20-59 years) in the city of Cuiaba, Brazil. Socioeconomic, demographic, and anthropometric data, as well as information on the lifestyle of the participants, were collected. In this study, waist circumference and waist-to-hip ratio were used as markers of abdominal fat. The association between these two markers and smoking was analyzed by multiple linear regression in separate models, adjusted for potential confounders. RESULTS: Of the 1,235 respondents, 273 (22.1%) reported being smokers, and, of those, 99 (36.3%) reported smoking more than 15 cigarettes per day. The average body mass index was lower among smokers than among nonsmokers (p < 0.001). In the multiple linear regression analyses, smoking was associated with waist circumference and waist-to-hip ratio for smokers of 6-10 cigarettes/day and of > 11 cigarettes/day. CONCLUSIONS: In our sample, smoking was positively associated with indicators of abdominal fat, regardless of potential confounding factors, including the consumption of alcoholic beverages. PMID- 22782607 TI - Impact of a mechanical ventilation weaning protocol on the extubation failure rate in difficult-to-wean patients. AB - OBJECTIVE: To determine whether the predictive accuracy of clinical judgment alone can be improved by supplementing it with an objective weaning protocol as a decision support tool. METHODS: This was a multicenter prospective cohort study carried out at three medical/surgical ICUs. The study involved all consecutive difficult-to-wean ICU patients (failure in the first spontaneous breathing trial [SBT]), on mechanical ventilation (MV) for more than 48 h, admitted between January of 2002 and December of 2005. The patients in the protocol group (PG) were extubated after a T-piece weaning trial and were compared with patients who were otherwise extubated (non-protocol group, NPG). The primary outcome measure was reintubation within 48 h after extubation. RESULTS: We included 731 patients 533 (72.9%) and 198 (27.1%) in the PG and NPG, respectively. The overall reintubation rate was 17.9%. The extubation success rates in the PG and NPG were 86.7% and 69.6%, respectively (p < 0.001). There were no significant differences between the groups in terms of age, gender, severity score, or pre-inclusion time on MV. However, COPD was more common in the NPG than in the PG (44.4% vs. 17.6%; p < 0.001), whereas sepsis and being a post-operative patient were more common in the PG (23.8% vs. 11.6% and 42.4% vs. 26.4%, respectively; p < 0.001 for both). The time on MV after the failure in the first SBT was higher in the PG than in the NPG (9 +/- 5 days vs. 7 +/- 2 days; p < 0.001). CONCLUSIONS: In this sample of difficult-to-wean patients, the use of a weaning protocol improved the decision-making process, decreasing the possibility of extubation failure. PMID- 22782608 TI - Thirty years of prophylactic cranial irradiation in patients with small cell lung cancer: a meta-analysis of randomized clinical trials. AB - OBJECTIVE: To determine the role of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC). METHODS: We searched various databases, selecting randomized clinical trials published in journals or conference proceedings within the last 30 years and investigating the role of PCI in the mortality of patients with SCLC, submitted to PCI or not. RESULTS: Sixteen randomized clinical trials, collectively involving 1,983 patients, were considered eligible for inclusion. Of those 1,983 patients, 1,021 were submitted to PCI and 962 were not. Overall mortality was 4.4% lower in the patients submitted to PCI than in those who were not (OR = 0.73; 95% CI: 0.57-0.97; p = 0.01), especially among the patients showing a complete response after induction chemotherapy (OR = 0.68; 95% CI: 0.50-0.93; p = 0.02) and in those submitted to PCI after that treatment (OR = 0.68; 95% CI: 0.49-0.94; p = 0.03). That decrease did not correlate with the stage of the disease: limited disease (OR = 0.73; 95% CI: 0.55-0.97; p = 0.03); and extensive disease (OR = 0.48; 95% CI: 0.26-0.87; p = 0.02). CONCLUSIONS: Our findings suggest that PCI decreases mortality in patients with SCLC, especially in those showing a complete response after induction chemotherapy and in those submitted to PCI after that treatment, regardless of the stage of the disease. PMID- 22782609 TI - Prevalence of HIV infection in tuberculosis patients treated at primary health care clinics in the city of Fortaleza, Brazil. AB - The objective of this study was to determine the prevalence of HIV infection among individuals >=15 years of age with a confirmed diagnosis of tuberculosis and treated at family health care clinics in the city of Fortaleza, Brazil. We evaluated a random sample of 110 patients with tuberculosis, treated at a total of 26 family health care clinics between January and May of 2009. All of the participants completed a questionnaire regarding sociodemographic and clinical data, and all underwent HIV testing. In this sample, the prevalence of tuberculosis/HIV co-infection was 3.6% (95% CI: 0.2-7.0). PMID- 22782610 TI - Severe tuberculosis requiring ICU admission. AB - Tuberculosis is a curable disease that can evolve to severe forms, requiring the treatment of the patients in an ICU, especially if there is a delay in the diagnosis or if it affects elderly patients, those on dialysis, or those with HIV infection or other states of immunosuppression, as well as in cases of multidrug resistant disease. Knowledge of the radiological presentation of the cases can help diagnose these severe forms, as can the introduction of new tests, such as the early detection of the etiological agent by PCR and chest CT, which favors the early initiation of treatment. In addition, the use of regimens without isoniazid and rifampin, as well as uncertain enteral absorption and low serum concentrations of antituberculosis drugs, can reduce the efficacy of treatment. For such patients, the prognosis is generally poor and mortality rates are high. PMID- 22782611 TI - Bronchiolitis associated with exposure to artificial butter flavoring in workers at a cookie factory in Brazil. AB - OBJECTIVE: To report the cases of four patients with bronchiolitis caused by exposure to artificial butter flavoring at a cookie factory in Brazil. METHODS: We described the clinical, tomographic, and spirometric findings in the four patients, as well as the lung biopsy findings in one of the patients. RESULTS: All four patients were young male nonsmokers and developed persistent airflow obstruction (reduced FEV1/FVC ratio and FEV1 at 25-44% of predicted) after 1-3 years of exposure to diacetyl, without the use of personal protective equipment, at a cookie factory. The HRCT findings were indicative of bronchiolitis. In one patient, the surgical lung biopsy revealed bronchiolitis obliterans accompanied by giant cells. CONCLUSIONS: Bronchiolitis resulting from exposure to artificial flavoring agents should be included in the differential diagnosis of airflow obstruction in workers in Brazil. PMID- 22782612 TI - Pleural effusion following ovarian hyperstimulation. AB - Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication that occurs in the luteal phase of an induced hormonal cycle. In most cases, the symptoms are self-limited and spontaneous regression occurs. However, severe cases are typically accompanied by acute respiratory distress. The objective of the present study was to describe the clinical presentation, treatment, and outcome of pleural effusion associated with OHSS in three patients undergoing in vitro fertilization. The patients ranged in age from 27 to 33 years. The onset of symptomatic pleural effusion (bilateral in all cases) occurred, on average, 43 days (range, 27-60 days) after initiation of hormone therapy for ovulation induction. All three patients required hospitalization for massive fluid resuscitation, and two required noninvasive mechanical ventilation. Although all three patients initially underwent thoracentesis, early recurrence of symptoms and pleural effusion prompted the use of drainage with a pigtail catheter. Despite the high output from the pleural drain (mean, 1,000 mL/day in the first week) and prolonged drainage (for 9-22 days), the outcomes were excellent: all three patients were discharged from hospital. Although pleural effusion secondary to OHSS is probably underdiagnosed, the associated morbidity should not be underestimated, especially because it affects potentially pregnant patients. In this study, early diagnosis and appropriate supportive measures yielded favorable results, limiting the surgical approach to adequate pleural drainage. PMID- 22782613 TI - Spontaneous pneumomediastinum (Hamman's syndrome). PMID- 22782614 TI - Report of two cases of ARDS patients treated with pumpless extracorporeal interventional lung assist. PMID- 22782615 TI - Pulmonary hemosiderosis associated with celiac disease: improvement after a gluten-free diet. PMID- 22782616 TI - Pregnancy as a risk factor for hospitalization due to pandemic influenza A (H1N1) 2009. PMID- 22782617 TI - Microbial transformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus. AB - The biotransformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus MT 5.3 yielded a rare derivative that was elucidated by spectrometric methods. The fungus led to the formation of a different product through an unusual epoxidation reaction between C4 and C5, formation of a C3,C10 ether bridge, and a methoxylation of the C1 of tagitinin C. The chemical structure of the product, namely 1beta-methoxy-3alpha-hydroxy-3,10beta-4,5alpha diepoxy-8beta-isobutyroyloxygermacr-11(13)-en-6alpha,12-olide, is the same as that of a derivative that was recently isolated from the flowers of a Brazilian population of Mexican sunflower (Tithonia diversifolia), which is the source of the substrate tagitinin C. The in vitro cytotoxic activity of the substrate and the biotransformed product were evaluated in HL-60 cells using an MTT assay, and both compounds were found to be cytotoxic. We show that soil fungi may be useful in the biotransformation of sesquiterpene lactones, thereby leading to unusual changes in their chemical structures that may preserve or alter their biological activities, and may also mimic plant biosynthetic pathways for production of secondary metabolites. PMID- 22782618 TI - Holmium laser ablation of the prostate (HoLAP): intermediate-term results of 144 patients. AB - PURPOSE: To retrospectively analyse the intermediate-term outcome of holmium laser ablation of the prostate (HoLAP) of up to 4 years postoperatively in one of the largest series and to define the selection criteria for patients who benefit from potentially lower complications associated with HoLAP. METHODS: Between June 2006 and November 2010, 144 patients with benign prostatic obstruction were treated at two centres with standardised HoLAP (2.0 J/50 Hz or 3.2 J/25 Hz with Versapulse((r)) 80-100 W laser Lumenis((r))). Median follow-up was 21 months (range, 1-54). International prostate symptom score and quality of life (IPSS QoL), PSA, prostate volume, maximal flow rate (Qmax), postvoiding residual volume (Vres) were evaluated pre- and postoperatively. All complications were graded according to CTCAE (v4.03). RESULTS: Mean patient age was 70.1 +/- 7.7 years (range, 46-90). With a preoperative median prostate volume of 40 ml (range, 10 130), the median operation time was 50 min (range, 9-138). We observed a median catheterisation time of 1 day (range, 0-12) and hospitalisation time of 2 days (range, 1-16). IPSS-QoL, Qmax and Vres were significantly improved after 3 months, and all parameters remained unchanged after 12, 24 and 36 months. The rate of re-operation was significantly lower in patients with prostate volume <40 ml, compared to patients with prostates >= 40 ml (9.1 vs. 25 %, p = 0.04). CONCLUSIONS: HoLAP is a safe and effective procedure for the treatment of prostates <40 ml. Patients benefit from HoLAP because of a low bleeding rate and short hospital stay. Due to high recurrence rates, HoLAP should be avoided in prostates >40 ml. PMID- 22782619 TI - Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. AB - Special (lipid) delivery: The role of the ionizable lipid pK(a) in the in vivo delivery of siRNA by lipid nanoparticles has been studied with a large number of head group modifications to the lipids. A tight correlation between the lipid pK(a) value and silencing of the mouse FVII gene (FVII ED(50) ) was found, with an optimal pK(a) range of 6.2-6.5. The most potent cationic lipid from this study has ED(50) levels around 0.005 mg kg(-1) in mice and less than 0.03 mg kg(-1) in non-human primates. PMID- 22782620 TI - The ubiquitin-proteasome system in positive-strand RNA virus infection. AB - Positive-stranded RNA viruses, like many other viruses, have evolved to exploit the host cellular machinery to their own advantage. In eukaryotic cells, the ubiquitin-proteasome system (UPS) that serves as the major intracellular pathway for protein degradation and modification plays a crucial role in the regulation of many fundamental cellular functions. A growing amount of evidence has suggested that the UPS can be utilized by positive-sense RNA viruses. The UPS eliminates excess viral proteins that prevent viral replication and modulates the function of viral proteins through post-translational modification mediated by ubiquitin or ubiquitin-like proteins. This review will discuss the current understanding of how positive RNA viruses have evolved various mechanisms to usurp the host UPS to modulate the function and stability of viral proteins. In addition to the pro-viral function, UPS-mediated viral protein degradation may also constitute a host defense process against some positive-stranded RNA viral infections. This issue will also be discussed in the current review. PMID- 22782621 TI - Hydrogen-bonding induced alternate stacking of donor (D) and acceptor (A) chromophores and their supramolecular switching to segregated states. AB - This paper reports comprehensive studies on the mixed assembly of bis (trialkoxybenzamide)-functionalized dialkoxynaphthalene (DAN) donors and naphthalene-diimide (NDI) acceptors due the cooperative effects of hydrogen bonding, charge-transfer (CT) interactions, and solvophobic effects. A series of DAN as well as NDI building blocks have been examined (wherein the relative distance between the two amide groups in a particular chromophore is the variable structural parameter) to understand the structure-dependent variation in mode of supramolecular assembly and morphology (organogel, reverse vesicle, etc.) of the self-assembled material. Interestingly, it was observed that when the amide functionalities are introduced to enhance the self-assembly propensity, the mode of co-assembly among the DAN and NDI chromophores no longer remained trivial and was dictated by a relatively stronger hydrogen-bonding interaction instead of a weak CT interaction. Consequently, in a highly non-polar solvent like methylcyclohexane (MCH), although kinetically controlled CT-gelation was initially noticed, within a few hours the system sacrificed the CT-interaction and switched over to the more stable self-sorted gel to maximize the gain in enthalpy from the hydrogen-bonding interaction. In contrast, in a relatively less non-polar solvent such as tetrachloroethylene (TCE), in which the strength of hydrogen bonding is inherently weak, the contribution of the CT interaction also had to be accounted for along with hydrogen bonding leading to a stable CT-state in the gel or solution phase. The stability and morphology of the CT complex and rate of supramolecular switching (from CT to segregated state) were found to be greatly influenced by subtle structural variation of the building blocks, solvent polarity, and the DAN/NDI ratio. For example, in a given D-A pair, by introducing just one methylene unit in the spacer segment of either of the building blocks a complete change in the mode of co-assembly (CT state or segregated state) and the morphology (1D fiber to 2D reverse vesicle) was observed. The role of solvent polarity, structural variation, and D/A ratio on the nature of co-assembly, morphology, and the unprecedented supramolecular-switching phenomenon have been studied by detail spectroscopic and microscopic experiments in a gel as well as in the solution state and are well supported by DFT calculations. PMID- 22782622 TI - A novel strategy for identification of 47 pomegranate (Punica granatum) cultivars using RAPD markers. AB - DNA marker can be used for precise plant cultivar identification. However, DNA markers have often not been used effectively for the identification of plant cultivars due to a lack of an effective analysis strategy. We used a novel strategy for effective identification of plant individuals based on a new way of recording DNA fingerprints of the genotyped plants; a cultivar identification diagram can be manually generated and used as key reference information for quick identification of plant and/or seed samples. Forty-seven pomegranate varieties popularly cultivated in various provinces of China were subjected to RAPD marker analysis. Using the cultivar identification diagram strategy, they were clearly separated by the fingerprints of 11 RAPD primers. The utility and accuracy of the cultivar identification diagram analysis results were confirmed by the identification of three randomly chosen groups of cultivars among the 47 varieties. PMID- 22782624 TI - Transcriptomic profiles of Japanese medaka (Oryzias latipes) in response to alkalinity stress. AB - Oryzias latipes (Adrianichthyidae), known as Japanese medaka or Japanese killifish, is a small 2-4 cm long fish common in rice paddies in coastal Southeast Asia and is also a popular aquarium fish. It has been widely used as a research model because of its small size and because it is very easy to rear. Alkalinity stress is considered to be one of the major stressors on fish in saline-alkaline water. As very little is known about molecular genetic responses of aquatic organisms to alkalinity stress, we examined genome-wide gene expression profiles of Japanese medaka in response to carbonate alkalinity stress. Adult fish were exposed to freshwater and high carbonate alkaline water in the laboratory. We designed a microarray containing 26,429 genes for measuring gene expression change in the gills of the fish exposed to high carbonate alkalinity stress. Among these genes, 512 were up-regulated and 501 were down-regulated in the gills. These differentially expressed genes can be divided into gene groups using gene ontology, including biological processes, cellular components and molecular function. These gene groups are related to acid-base and ion regulation, cellular stress response, metabolism, immune response, and reproduction processes. Biological pathways including amino sugar and nucleotide sugar metabolism, porphyrin and chlorophyll metabolism, metabolism of xenobiotics by cytochrome P450, drug metabolism, aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, ascorbate and aldarate metabolism, pentose and glucuronate interconversions, glutathione metabolism, and fructose and mannose metabolism were significantly up-regulated. Alkalinity stress stimulates the energy and ion regulation pathways, and it also slows down the pathways related to the immune system and reproduction. PMID- 22782625 TI - Relationships between four measures of genetic distance and breeding behavior in spring wheat. AB - We estimated the genetic distances among 10 spring wheat genotypes based on pedigree data, morphological traits and AFLP markers, used individually and combined with morphological traits, to find the best predictors of general- and specific-combining abilities among parental genotypes. Ten wheat parents were crossed in a diallel form, disregarding reciprocal hybrids, totaling 45 combinations. The F1 hybrids, F2 populations and parents were evaluated in the field in 2007. The experimental plots consisted of 20 plants for F1 hybrids and 40 plants for parental and F2 populations. All methods (pedigree data, AFLP markers and morphological traits, used individually and combined) were found to be useful for the assessment of genetic diversity. The significant coefficient correlations ranged from low (0.45) to moderate (0.67) between the distance measures and hybrid performance. There was significant agreement between the distance measures based on AFLP markers vs morphological traits + AFLP markers (r = 0.47) and between pedigree data vs morphological traits + AFLP markers (r = 0.43). The pedigree distance was positively associated with traits 100-kernel weight and grain yield per plant in F1 (correlations of 0.67 and 0.62, respectively) and F2 (correlations of 0.62 and 0.59, respectively) generations. These correlation values indicate that the genetic distance, based on pedigree data, could replace diallel crosses for the selection of parents with higher combining ability and with moderate reliability. PMID- 22782627 TI - Cytogenetics of the darkling beetles Zophobas aff. confusus and Nyctobates gigas (Coleoptera, Tenebrionidae). AB - Males of Zophobas aff. confusus and Nyctobates gigas (Tenebrionidae) collected in the State of Pernambuco, Brazil, were studied through conventional staining, C banding, silver nitrate impregnation (AgNO3), and the base specific fluorochromes CMA3 and DAPI. Z. aff. confusus was found to have 2n = 20 (9+Xyp) while N. gigas exhibited 2n = 18 (8+neoXY). Large pericentromeric blocks of constitutive heterochromatin (CH) were detected throughout the autosomal complement of the two species, except in one autosomal pair of N. gigas in which no heterochromatic block was observed. The sex chromosomes of both species were almost totally heterochromatic. Double staining with CMA3/DA (distamycin) and DAPI/DA marked CH in Z. aff. confusus. However, DAPI staining was more intense. N. gigas was found to possess blocks of CH-positive CMA3 and homogeneous DAPI. AgNO3 staining also revealed differences between the two species. In Z. confusus an NOR was observed in the sexual bivalent Xyp and N. gigas was found to have an autosomal NOR. PMID- 22782626 TI - Molecular characterization of an opossum Didelphis albiventris (Marsupialia: Didelphidae) population in an urban fragment of the Brazilian Atlantic rainforest and support to species barcode identification. AB - We made a molecular study of 40 opossums, Didelphis albiventris, from an urban fragment of the Atlantic Rainforest in southeastern Brazil, analyzing a 653-bp sequence of cytochrome c oxidase, subunit I. We found three close connected haplotypes, with low nucleotide diversity and a haplotype diversity of 59.1% and confirmed sympatry between D. albiventris and D. aurita in this region. The clear phylogenetic separation shows the appropriateness of DNA barcode identification methodology for effectively discriminating between these opossum species. PMID- 22782628 TI - Identification of ANAPC13 gene polymorphisms associated with body measurement traits in Bos taurus. AB - Body measurement traits, influenced by genes and environmental factors, play numerous important roles in the value assessment of productivity and economy. There has been some indication that ANAPC13 influences adult height. We used PCR SSCP and DNA sequencing technology to identify polymorphisms in the ANAPC13 gene. A polymorphism in intron 1 (A > G at base 17) was identified and an additional polymorphic site (C > T at base 42) was also uncovered, which accompanied the previous polymorphism in more than 98% of the subjects. The two novel polymorphisms in exon 1 were assayed and potential associations with body measurement traits were evaluated in 404 individuals. Three genotypes were detected in the study group, named AACC, AGCT and GGTT. Significant differences were observed between genotypes AACC and AGCT for body length, withers height, hip height, hip width, heart girth, pin bone width. However, no associations were found among any genotypes and chest depth. We conclude that polymorphisms and mutations in non-coding regions of the ANAPC13 gene significantly affect body measurement traits. PMID- 22782629 TI - Genetic polymorphisms of EGF 5'-UTR and NAT2 857G/A associated with glioma in a case control study of Malaysian patients. AB - Studies of genetic mutations that have been used in predicting glioma prognosis have revealed a complex relationship between clinical and genetic factors. Epidermal growth factor (EGF) and the NAT2 gene play a central role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production, and the mutations in the NAT2 gene have been postulated as a risk factor for cancer. We investigated EGF and the NAT2 gene in 13 glioma tissue samples and 12 normal controls. In the EGF 5'-UTR 61G polymorphism, the heterozygote GA was the most common genotype in the glioma patients. In the NAT2 polymorphism at nucleotide position 857G/A, the G allele and the GG genotype were the most prevalent forms in both the glioma and normal samples. We did not find any homozygous AA genotypes in the glioma patients. Based on this preliminary evidence, the EGF 5'-UTR at position 61 and the NAT2 SNP at position 857 polymorphisms are associated with increased risk for glioma. PMID- 22782630 TI - Phylogenetic diversity of endophytic leaf fungus isolates from the medicinal tree Trichilia elegans (Meliaceae). AB - Various types of organisms, mainly fungi and bacteria, live within vegetal organs and tissues, without causing damage to the plant. These microorganisms, which are called endophytes, can be useful for biological control and plant growth promotion; bioactive compounds from these organisms may have medical and pharmaceutical applications. Trichilia elegans (Meliaceae) is a native tree that grows abundantly in several regions of Brazil. Preparations using the leaves, seeds, bark, and roots of many species of the Meliaceae family have been widely used in traditional medicine, and some members of the Trichilia genus are used in Brazilian popular medicine. We assessed the diversity of endophytic fungi from two wild specimens of T. elegans, collected from a forest remnant, by sequencing ITS1-5.8S-ITS2 of rDNA of the isolates. The fungi were isolated and purified; 97 endophytic fungi were found; they were separated into 17 morpho groups. Of the 97 endophytic fungi, four genera (Phomopsis, Diaporthe, Dothideomycete, and Cordyceps) with 11 morpho-groups were identified. Phomopsis was the most frequent genus among the identified endophytes. Phylogenetic analysis showed two major clades: Sordariomycetes, which includes three genera, Phomopsis, Diaporthe, and Cordyceps, and the clade Dothideomycetes, which was represented by the order Pleosporales. PMID- 22782631 TI - A rapid method to increase the number of F1 plants in pea (Pisum sativum) breeding programs. AB - In breeding programs, a large number of F2 individuals are required to perform the selection process properly, but often few such plants are available. In order to obtain more F2 seeds, it is necessary to multiply the F1 plants. We developed a rapid, efficient and reproducible protocol for in vitro shoot regeneration and rooting of seeds using 6-benzylaminopurine. To optimize shoot regeneration, basic medium contained Murashige and Skoog (MS) salts with or without B5 Gamborg vitamins and different concentrations of 6-benzylaminopurine (25, 50 and 75 MUM) using five genotypes. We found that modified MS (B5 vitamins + 25 MUM 6 benzylaminopurine) is suitable for in vitro shoot regeneration of pea. Thirty eight hybrid combinations were transferred onto selected medium to produce shoots that were used for root induction on MS medium supplemented with alpha naphthalene-acetic acid. Elongated shoots were developed from all hybrid genotypes. This procedure can be used in pea breeding programs and will allow working with a large number of plants even when the F1 plants produce few seeds. PMID- 22782623 TI - Transcript profiling of expressed sequence tags from semimembranosus muscle of commercial and naturalized pig breeds. AB - In general, genetic differences across different breeds of pig lead to variation in mature body size and slaughter age. The Commercial breeds Duroc and Large White and the local Brazilian breed Piau are ostensibly distinct in terms of growth and muscularity, commercial breeds are much leaner while local breeds grow much slower and are fat type pigs. However, the genetic factors that underlie such distinctions remain unclear. We used expressed sequence tags (ESTs) to characterize and compare transcript profiles in the semimembranosus muscle of these pig breeds. Our aim was to identify differences in breed-related gene expression that might influence growth performance and meat quality. We constructed three non-normalized cDNA libraries from semimembranosus muscle, using two samples from each one, of these three breeds; 6902 high-quality ESTs were obtained. Cluster analysis was performed and these sequences were clustered into 3670 unique sequences; 24.7% of the sequences were categorized as contigs and 75.3% of the sequences were singletons. Based on homology searches against the SwissProt protein database, we were able to assign a putative protein identity to only 1050 unique sequences. Among these, 58.5% were full-length protein sequences and 17.2% were pig-specific sequences. Muscle structural and cytoskeletal proteins, such as actin, and myosin, were the most abundant transcripts (16.7%) followed by those related to mitochondrial function (12.9%), and ribosomal proteins (12.4%). Furthermore, ESTs generated in this study provide a rich source for identification of novel genes and for the comparative analysis of gene expression patterns in divergent pig breeds. PMID- 22782632 TI - Molecular characterization and functional analysis of sheep thyroid transcription factor-1. AB - Thyroid transcription factor-1 (TTF-1), a member of the Nkx2 family of homeodomain-containing proteins, is involved in binding to and in activating the promoters of several important genes in the thyroid, lungs, and brain, and in regulating expression of these tissue-specific genes. We investigated potential roles of sheep (Ovis aries) TTF-1 in regulating cell fate and organ morphogenesis and in controlling puberty and reproductive capability of females. We amplified and cloned the sheep TTF-1 full-length DNA for the first time, analyzed its functional domains and regions, predicted molecular structure of its homeodomain and DNA-binding sites, and examined its expression in pituitary, brain, thyroid gland, ovary, and hypothalamus. We found that sheep TTF-1 has a high degree of homologous identity with that of other mammals, and it has several important domains including domain N, DNA-binding domain, domain C, TN domain, domain I, and NK2-SD. The DNA-binding domain of sheep TTF-1 has 10 potential DNA-binding sites and is a novel mammalian homeodomain that shows considerable sequence homology with the corresponding rat homeodomain. Several functional regions in sheep TTF-1 share high sequence identity with rat TTF-1, indicating that these regions may have the same activity as in the rat. Expression of TTF-1 in several specific tissues implies that sheep TTF-1 in involved in sheep sexual development and reproductive capability. These results suggest a role of sheep TTF-1 in enhancing sheep reproduction performance and we propose it as a candidate gene for selection. PMID- 22782633 TI - Suitable internal control microRNA genes for measuring miRNA abundance in pig milk during different lactation periods. AB - Determination of an optimal set/number of internal control microRNA (miRNA) genes is a critical, but often undervalued, detail of quantitative gene expression analysis. No validated internal genes for miRNA quantitative PCR (q PCR) in pig milk were available. We compared the expression stability of six porcine internal control miRNA genes in pig milk from different lactation periods (1 h, 3 days, 7 days, 14 days, 21 days, and 28 days postpartum), using an EvaGreen q-PCR approach. We found that using the three most stable internal control genes to calculate the normalization factor is sufficient for producing reliable q-PCR expression data. We also found that miRNAs are superior to ribosomal RNA (rRNA) and snRNA, which are commonly used as internal controls for normalizing miRNA q-PCR data. In terms of economic and experimental feasibility, we recommend the use of the three most stable internal control miRNA genes (miR 17, -107 and -103) for calculating the normalization factors for pig milk samples from different lactation periods. These results can be applied to future studies aimed at measuring miRNA abundance in porcine milk. PMID- 22782634 TI - Assessment of genetic diversity of landraces of Dendrocalamus hamiltonii using AFLP markers and association with biochemical traits. AB - Fermented bamboo shoots are popular traditional food items of various ethnic groups of the northeastern India, especially in Manipur State. Dendrocalamus hamiltonii is an economically important bamboo species used to produce fermented bamboo shoots. We studied genetic variability of this bamboo species in Chandel and Imphal-East (commercial production districts), using AFLP molecular markers. Each of the selected primers detected polymorphisms and 1614 (95.8%) were found to be polymorphic. Cluster analysis based on Dice similarity coefficients using UPGMA differentiated the populations into two major groups. Principal coordinate analysis based on the AFLP data clearly separated the populations according to their genetic diversity and antioxidant activity. Four primers were tested through multiple regression analysis to identify marker-trait association between AFLP data and biochemical attributes, i.e., antioxidant activity and total cyanide content. The 273 bp generated by EcoRI-AAG(Joe)/MseI-CTC showed high positive correlation with antioxidant activity (r = 0.729, P < 0.01). The 396 bp generated by EcoRI-AAC(Ned)/MseI-CTG were negatively correlated with cyanide content (r = -0.694, P < 0.01). Thus, we found association of DNA markers with antioxidant activities and total cyanide content. These results could be of use for the identification of superior genotypes with desirable traits. PMID- 22782635 TI - Effect of different carbon sources on proteases secreted by the fungal pathogen Sclerotinia sclerotiorum during Phaseolus vulgaris infection. AB - Sclerotinia sclerotiorum (Sclerotiniaceae) is a plant pathogenic fungus that causes white mold disease in vegetable crops, including the common bean (Phaseolus vulgaris). Proteases produced by fungi are normally an important part of the pathogenic process in the host. We examined the effect of different carbon sources--pectin, glucose, and cell wall of P. vulgaris on the production of proteases in cultures of S. sclerotiorum. These proteases were also assayed in infected P. vulgaris plants. Enzyme activity was increased with all carbon sources, but the highest levels were found when pectin was added. Based on real time quantitative reverse transcription-PCR analyses, protease induction in S. sclerotiorum was found to occur at the level of gene transcription. The finding of increased expression of acid phosphatase 1 and aspartyl protease in vivo in infected P. vulgaris plants supports the role of these enzymes in the invasion process of S. sclerotiorum. PMID- 22782636 TI - Genetic diversity and population structure of Chinese pony breeds using microsatellite markers. AB - China is one of the principal origins of ponies in the world. We made a comprehensive analysis of genetic diversity and population structure of Chinese ponies based on 174 animals of five indigenous Chinese pony breeds from five provinces using 13 microsatellite markers. One hundred and forty-four alleles were detected; the mean number of effective alleles among the pony breeds ranged from 5.38 (Guizhou) to 6.78 (Sichuan); the expected heterozygosity ranged from 0.82 (Guizhou) to 0.85 (Debao, Sichuan). Although abundant genetic variation was found, the genetic differentiation was low between the ponies, with 6% total genetic variance among the different breeds. All the pairwise F(ST) values were significant; they varied from 0.0424 for the Sichuan-Yunnan pair to 0.0833 for the Guizhou-Sichuan pair. All five pony breeds deviated from Hardy-Weinberg equilibrium, except the Yunnan pony. Phylogenetic trees of the five pony breeds based on genetic distances were constructed using a neighbor-joining method. The Sichuan and Yunnan ponies were grouped into the same branch, with a high bootstrap support value (97%). Guizhou and Ningqiang ponies were clustered into the same branch with a bootstrap value of 56%, whereas the Debao pony was placed in a separate group, with a bootstrap value of 56%. This grouping pattern was supported by genetic structure analysis. PMID- 22782637 TI - Genetic diversity and phylogeny of rhizobia isolated from Caragana microphylla growing in desert soil in Ningxia, China. AB - Rhizobia are soil bacteria with the capacity to induce nitrogen-fixing nodules on the roots or stems of legume plants. A total of 40 bacterial isolates from the root nodules of Caragana microphylla growing in desert soil in Ningxia, China, were analyzed for genetic diversity and phylogenetic position. These isolates were classified into 7 types of 16S ribosomal DNA (rDNA) using polymerase chain reaction-restriction fragment length polymorphism analysis. They were grouped into 4 clades, Rhizobium-Agrobacterium, Sinorhizobium, Phyllobacterium, and Bradyrhizobium, when the phylogenies of 16S rDNA, recA, and atpD genes were applied. Phylogenetic analysis showed that the tree generated from the 16S rDNA sequencing agreed with that produced from the recA and atpD genes. By analyzing phylogenetic relationship using the 3 loci, the isolates in the branches of Phyllobacterium and Sinorhizobium could be identified as P. brassicacearum and S. meliloti. The isolates in the branch of Rhizobium Agrobacterium were the most abundant microsymbiont of C. microphylla and were designated R. leguminosarum, R. galegae, R. alamii, and A. tumefaciens. Two isolates with low sequence similarity to the known species of Bradyrhizobium might be novel species in this genus. PMID- 22782638 TI - Antiquity, botany, origin and domestication of Jatropha curcas (Euphorbiaceae), a plant species with potential for biodiesel production. AB - Jatropha curcas is a multi-purpose plant species, with many advantages for biodiesel production. Its potential oil productivity is 1.9 t/ha, beginning the fourth year after planting. Nevertheless, limitations such as high harvest cost, lack of scientific konowledge and low profitability have prevented it from being utilized commercially. In order to provide information that could be useful to improve the status of this species as a bioenergy plant, we elucidated the center of origin and the center of domestication of J. curcas (Mexico). Evidence of the antiquity of knowledge of J. curcas by Olmeca people, who lived 3500-5000 years ago, reinforces its Mexican origin. The existence of non-toxic types, which only exist in that country, along with DNA studies, also strongly suggest that Mexico is the domestication center of this species. In Brazil, the Northern region of Minas Gerais State presents types with the highest oil content. Here we propose this region as a secondary center of diversity of J. curcas. PMID- 22782639 TI - Divergence of sperm and leukocyte age-dependent telomere dynamics: implications for male-driven evolution of telomere length in humans. AB - Telomere length (TL) dynamics in vivo are defined by TL and its age-dependent change, brought about by cell replication. Leukocyte TL (LTL), which reflects TL in hematopoietic stem cells (HSCs), becomes shorter with age. In contrast, sperm TL, which reflects TL in the male germ cells, becomes longer with age. Moreover, offspring of older fathers display longer LTL. Thus far, no study has examined LTL and sperm TL relations with age in the same individuals, nor considered their implications for the paternal age at conception (PAC) effect on offspring LTL. We report that in 135 men (mean age: 34.4 years; range: 18-68 years) on average, LTL became shorter by 19 bp/year (r = -0.3; P = 0.0004), while sperm TL became longer by 57 bp/year (r = 0.32; P = 0.0002). Based on previously reported replication rates of HSCs and male germ cells, we estimate that HSCs lose 26 bp per replication. However, male germ cells gain only 2.48 bp per replication. As TL is inherited in an allele-specific manner, the magnitude of the PAC effect on the offspring's LTL should be approximately half of age-dependent sperm-TL elongation. When we compared the PAC effect data from previous studies with sperm TL data from this study, the result was consistent with this prediction. As older paternal age is largely a feature of contemporary humans, we suggest that there may be progressive elongation of TL in future generations. In this sense, germ cell TL dynamics could be driving the evolution of TL in modern humans and perhaps telomere-related diseases in the general population. PMID- 22782640 TI - Comprehensive tuberculosis screening program in patients with inflammatory arthritides treated with golimumab, a human anti-tumor necrosis factor antibody, in Phase III clinical trials. AB - OBJECTIVE: Reactivation of Mycobacterium tuberculosis infection is a major complication in patients treated with anti-tumor necrosis factor (anti-TNF) agents. We report on the 5 cases of active tuberculosis (TB) that developed in the Golimumab Phase III Program (3 with rheumatoid arthritis, 1 with psoriatic arthritis, and 1 with ankylosing spondylitis) through 1 year among 2,210 patients receiving golimumab. METHODS: Data from global studies were used for an in-depth evaluation of the 5 cases of TB through week 52. Integrated safety data were evaluated for potential hepatotoxicity in patients treated with anti-TB therapy. RESULTS: No active TB developed among 317 patients receiving golimumab and treated for latent TB with isoniazid. Active TB occurred in 5 patients not treated with isoniazid by week 52 (in 2 patients by week 24); all of the patients had negative TB screening tests (per the local guidelines) and resided in countries with high background rates of TB. No deaths were due to TB. Across all of the groups (placebo and golimumab), alanine aminotransferase and aspartate aminotransferase elevations occurred in greater proportions of patients treated for latent TB infection versus not treated; elevations were largely mild (<3 times the upper limit of normal). CONCLUSION: Comprehensive TB screening kept the number of active TB cases relatively low despite conducting the studies in TB endemic regions. Treatment for latent TB infection appeared effective, since no patients treated for latent TB had TB reactivation. Concurrent treatment with golimumab and anti-TB medication was generally well tolerated. Clinicians should remain vigilant for development of active TB after initiation of TNF inhibitors, since prompt diagnosis and treatment can improve outcomes. PMID- 22782641 TI - The effect of temperature on the structure and function of a cellulose-degrading microbial community. AB - The purpose of this study was to investigate the effect of temperature on the structure and straw degradation capability of a microbial community grown from wheat straw compost. Two cellulolytic microbial communities, WDC1 and WDC2, were obtained from compost. The communities had been cultured under 50 and 60 degrees C by continuous enrichment, respectively. The wheat straw degradation capabilities were 45.69 % (WDC1) and 59.5 % (WDC2). By changing the culture temperatures, two new stable communities were obtained: WDC1-6N (WDC1, cultivated at 60 degrees C for eight generations) and WDC2-5N (WDC2, cultivated at 50 degrees C for eight generations). The wheat straw degradation capabilities for the new communities were 59.75 and 52.60 %, respectively. The results showed that compared to 50 degrees C, the wheat straw degradation capability of the communities cultured at 60 degrees C was stronger. Sequencing of selected denaturing gradient gel electrophoresis (DGGE) bands and analysis of DGGE profiles indicated that the WDC2 structure was significantly different from the structure of WDC1. This was so even though the two communities were enriched from the same compost. With the change of culture temperature, the community structures underwent significant transitions. Included communities were thermophilic, anaerobic bacteria, and any cellulolytic bacteria (e.g., Clostridium thermocellum) that were active and abundant at conditions under 60 degrees C. These results have the potential to significantly aid in the enrichment of a cellulose-degrading community from the environment and to enhance the community capability to conduct straw biotransformation. PMID- 22782642 TI - Effect of pretreatment severity on accumulation of major degradation products from dilute acid pretreated corn stover and subsequent inhibition of enzymatic hydrolysis of cellulose. AB - The concept of reaction severity, which combines residence time and temperature, is often used in the pulp and paper and biorefining industries. The influence of corn stover pretreatment severity on yield of sugar and major degradation products and subsequent effects on enzymatic cellulose hydrolysis was investigated. The pretreatment residence time and temperature, combined into the severity factor (Log R(o)), were varied with constant acid concentration. With increasing severity, increasing concentrations of furfural and 5 hydroxymethylfurfural (5-HMF) coincided with decreasing yields of oligosaccharides. With further increase in severity factor, the concentrations of furans decreased, while the formation of formic acid and lactic acid increased. For example, from severity 3.87 to 4.32, xylose decreased from 6.39 to 5.26 mg/mL, while furfural increased from 1.04 to 1.33 mg/mL; as the severity was further increased to 4.42, furfural diminished to 1.23 mg/mL as formate rose from 0.62 to 1.83 mg/mL. The effects of dilute acid hydrolyzate, acetic acid, and lignin, in particular, on enzymatic hydrolysis were investigated with a rapid microassay method. The microplate method gave considerable time and cost savings compared to the traditional assay protocol, and it is applicable to a broad range of lignocellulosic substrates. PMID- 22782643 TI - Costs explained by function rather than diagnosis--results from the SNAC Nordanstig elderly cohort in Sweden. AB - BACKGROUND: Because the prevalence of many brain disorders rises with age, and brain disorders are costly, the economic burden of brain disorders will increase markedly during the next decades. AIM: The purpose of this study is to analyze how the costs to society vary with different levels of functioning and with the presence of a brain disorder. METHODS: Resource utilization and costs from a societal viewpoint were analyzed versus cognition, activities of daily living (ADL), instrumental activities of daily living (IADL), brain disorder diagnosis and age in a population-based cohort of people aged 65 years and older in Nordanstig in Northern Sweden. Descriptive statistics, non-parametric bootstrapping and a generalized linear model (GLM) were used for the statistical analyses. RESULTS: Most people were zero users of care. Societal costs of dementia were by far the highest, ranging from SEK 262,000 (mild) to SEK 519,000 per year (severe dementia). In univariate analysis, all measures of functioning were significantly related to costs. When controlling for ADL and IADL in the multivariate GLM, cognition did not have a statistically significant effect on total cost. The presence of a brain disorder did not impact total cost when controlling for function. The greatest shift in costs was seen when comparing no dependency in ADL and dependency in one basic ADL function. CONCLUSION: It is the level of functioning, rather than the presence of a brain disorder diagnosis, which predicts costs. ADLs are better explanatory variables of costs than Mini mental state examination. Most people in a population-based cohort are zero users of care. PMID- 22782644 TI - Differential capacitance of liquid/liquid interfaces of finite thicknesses: a finite element study. AB - Finite element simulations were used to investigate the effect of a smooth variation of permittivity across a polarized liquid/liquid interface on the differential capacitance. The results show that a relative permittivity profile can account for the variation of ion solvation in the interfacial region, and therefore upon the diffuse double layer itself. The width and the symmetry of this profile across the interface are shown to be crucial parameters for interfacial distributions and fitting of capacitance data has been used to estimate the width of the interfacial region. PMID- 22782645 TI - Life-threatening bleeding in four patients with an unusual excessive response to dabigatran: implications for emergency surgery and resuscitation. PMID- 22782646 TI - Bilateral transient myopia, angle-closure glaucoma, and choroidal detachment induced by methazolamide. AB - PURPOSE: We report the case of a patient with acute bilateral transient myopia, secondary angle-closure glaucoma, and choroidal detachment associated with oral administration of methazolamide. CASE: A 51-year-old man developed bilateral transient myopia and secondary angle-closure glaucoma with choroidal detachment after oral administration of methazolamide. Both eyes presented a shallow anterior chamber and elevated intraocular pressure. Ultrasound biomicroscopy revealed annular ciliochoroidal effusion and diffuse thickening of the ciliary body. Angiography showed many scattered islands of hypofluorescence in both eyes. OBSERVATIONS: Methazolamide was stopped and prednisolone given orally. Eight days after treatment initiation, clinical symptoms and signs had resolved. The abnormal findings on ultrasound biomicroscopy and angiography disappeared by 2 months. CONCLUSIONS: Methazolamide can induce bilateral transient myopia, angle closure glaucoma, and choroidal detachment. Prompt identification of the causative medications and subsequent discontinuation can induce rapid resolution of angle closure. PMID- 22782647 TI - 5S rRNA gene arrangements in protists: a case of nonadaptive evolution. AB - Given their high copy number and high level of expression, one might expect that both the sequence and organization of eukaryotic ribosomal RNA genes would be conserved during evolution. Although the organization of 18S, 5.8S and 28S ribosomal RNA genes is indeed relatively well conserved, that of 5S rRNA genes is much more variable. Here, we review the different types of 5S rRNA gene arrangements which have been observed in protists. This includes linkages to the other ribosomal RNA genes as well as linkages to ubiquitin, splice-leader, snRNA and tRNA genes. Mapping these linkages to independently derived phylogenies shows that these diverse linkages have repeatedly been gained and lost during evolution. This argues against such linkages being the primitive condition not only in protists but also in other eukaryote species. Because the only characteristic the diverse genes with which 5S rRNA genes are found linked with is that they are tandemly repeated, these arrangements are unlikely to provide any selective advantage. Rather, the observed high variability in 5S rRNA genes arrangements is likely the result of the fact that 5S rRNA genes contain internal promoters, that these genes are often transposed by diverse recombination mechanisms and that these new gene arrangements are rapidly homogenized by unequal crossingovers and/or by gene conversions events in species with short generation times and frequent founder events. PMID- 22782648 TI - In vitro and in vivo metabolic studies of phospho-aspirin (MDC-22). AB - PURPOSE: To investigate the metabolism of phospho-aspirin (PA, MDC-22), a novel anti-cancer and anti-inflammatory agent. METHODS: The metabolism of PA was studied in the liver and intestinal microsomes from mouse, rat and human. RESULTS: PA is rapidly deacetylated to phospho-salicylic acid (PSA), which undergoes regioselective oxidation to generate 3-OH-PSA and 5-OH-PSA. PSA also can be hydrolyzed to give salicylic acid (SA), which can be further glucuronidated. PA is far more stable in human liver or intestinal microsomes compared to those from mouse or rat due to its slowest deacetylation in human microsomes. Of the five major human cytochrome P450 (CYP) isoforms, CYP2C19 and 2D6 are the most active towards PSA. In contrast to PSA, conventional SA is not appreciably oxidized by the CYPs and liver microsomes, indicating that PSA is a preferred substrate of CYPs. Similarly, PA, in contrast to PSA, cannot be directly oxidized by CYPs and liver microsomes, indicating that the acetyl group of PA abrogates its oxidation by CYPs. CONCLUSIONS: Our findings establish the metabolism of PA, reveal significant inter-species differences in its metabolic transformations, and provide an insight into the role of CYPs in these processes. PMID- 22782649 TI - Parents' perspectives on participating in genetic research in autism. AB - Genetic research in autism depends on the willingness of individuals with autism to participate; thus, there is a duty to assess participants' needs in the research process. We report on families' motives and expectations related to their participation in autism genetic research. Respondents valued having a genetic result, as it alleviates guilt, promotes awareness, and may be used to tailor interventions and for family planning. The act of participating was distinctly significant, as it provided personal control, a connection to autism experts, networking with families, and hope for the future. The results of this study highlight complex factors involved in families' decisions to participate in autism genetic research and provide points to consider for this population of research participants. PMID- 22782650 TI - Microfluidic cell volume sensor with tunable sensitivity. AB - We report the fabrication and validation of a microfluidic cell volume sensor integrated on a multi-layered polydimethylsiloxane (PDMS) microchip with a tunable detection volume for dynamic control of sensitivity, enabling the detection of individual Escherichia coli and microparticles. PMID- 22782651 TI - Percutaneous endoscopic treatment of foraminal and extraforaminal disc herniation at the L5-S1 level. AB - BACKGROUND: Microsurgery of foraminal and extraforaminal disc herniation at the L5-S1 level remains a challenge because of the limited access by a high iliac crest, the sacral ala, large transverse processes of L5 and hidden disc fragments lateral to the zygapophyseal joint. Our aim was to present the outcome of percutaneous endoscopic lumbar discectomy (PELD) of these lateral and far lateral disc herniations at the L5-S1 level using the newly described foraminal retreat technique in a group of patients with similar preoperative diagnostic studies. METHODS: A total of 22 patients, 13 males and 9 females, with foraminal and extraforaminal lumbar disc herniation at the L5-S1 level were treated by applying the PELD between September 2004 and April 2010. The clinical findings and MRI were the main diagnostic methods. Preoperative evaluation was performed with clinical examinations, the Visual Analog Pain Scale (VAS) and Oswestry Low Back Disability Index (ODI). FINDINGS: According to the Macnab criteria, overall excellent or good outcomes were obtained in 18 patients (81.8 %), fair outcomes in 3 patients (13.6 %) and a poor outcome in 1 patient (4.5 %) at the last follow up. The mean ODI was 67.3 +/- 19.4 preoperatively and 26.7 +/- 23.4 postoperatively. Preoperative VAS was 88.6 +/- 7.6 and 28.6 +/- 22.8 at 2 days, 40.5 +/- 22.8 at 3 weeks, 34.3 +/- 25.1 at 6-months and 32 at the last follow-up. At follow-up, two patients (9.1 %) had recurrent disc herniations that were corrected with open surgery. At the time of surgery, 16 patients held jobs. Fifteen (15) patients (93.8 %) returned to their original jobs postoperatively; one patient could not return to his original job postoperatively because of a comorbidity. CONCLUSIONS: Percutaneous endoscopic discectomy using the foraminal retreat technique is an effective treatment method for patients with foraminal and extraforaminal disc herniations at the L5-S1 level on appropriately selected patients. PMID- 22782652 TI - The distribution of arachnoid membrane within the velum interpositum. AB - BACKGROUND: There is as yet little knowledge as to the arachnoid architecture within the velum interpositum. The aim of this study was to clarify the distribution of the arachnoid membrane within the velum interpositum and its relationship with the arachnoid envelope over the pineal region. METHODS: In seven adult cadaver heads, histological sections of the third ventricle roof, stained with Masson's trichrome stains, were studied under light microscopy. RESULTS: Within the velum interpositum, there are two arachnoid layers. The dorsal layer of arachnoid membrane envelops the internal cerebral veins and fixes them to the surrounding tela choroidea as well as the ventral arachnoid layer. The ventral layer of arachnoid membrane is a direct anterior extension of the arachnoid envelope over the pineal region and covers the midline inferior layer of tela choroidea. Both arachnoid layers end near the foramen of Monro. CONCLUSIONS: The membranous roof of the third ventricle comprises two layers of the tela choroidea and two arachnoid layers. These two arachnoid layers are derived from the arachnoid envelope over the pineal region. PMID- 22782653 TI - Autoimmune encephalitis associated with Graves' disease: a case report. AB - Almost all patients who developed autoimmune thyroid disease associated with encephalopathy were diagnosed to have Hashimoto's thyroiditis, but a few patients with Graves' disease who developed encephalopathy have been reported. A 36-year old female with a 10-year history of Graves' disease had experienced three episodes of tonic-clonic seizure. At admission, the patient's status was confused, and she also developed tactile and visual hallucinations. The cranial MRI confirmed white-matter lesion and showed subcortical high signal lesions on T2-weighted images. In EEG record, diffuse slow activity was noticed in both sides. T3 and TSH were decreased, T4 remained normal and thyroid peroxidase antibody (TPO) was evaluated to be more than 2,000 (T4 = 8.4, T3 = 12/9, TSH = 0/14, TPO >2,000). The diagnosis of autoimmune thyroid disease is probable in all patients with signs of encephalopathy with unknown origin, while they have a previous history of thyroid disease. PMID- 22782654 TI - KCNJ10 gene mutation in an 8-year-old boy with seizures. PMID- 22782655 TI - Very efficient generation of quinone methides through excited state intramolecular proton transfer to a carbon atom. AB - Irradiation of 2-phenyl-1-naphthol (6) in CH(3) CN/D(2) O (3:1) leads to very efficient incorporation of deuterium at the ortho-positions of the adjacent phenyl ring (overall Phi=0.73+/-0.07), along with minor incorporation at the naphthalene positions 5 and 8. These finding are explained by excited state intramolecular proton transfer (ESIPT) from the phenolic OH group to the corresponding carbon atoms, the main pathway giving rise to quinone methide (QM) 7, which has been characterized by LFP (tau~20 ns; 460 nm). The ESIPT reaction paths have been explored with the second order approximate coupled cluster (CC2) method. In nonprotic solvents the ESIPT from the naphthol O-H to the ortho position of the phenyl ring proceeds in a barrierless manner along the (1) L(a) energy surface via a conical intersection with the S(0) state, delivering 7. In aqueous solvent, clusters with H(2) O are formed wherein proton transfer (PT) to solvent and a H(2) O-mediated relay mechanism gives rise to naphtholates and QMs. The results are compared with 2-phenylphenol (3) that also undergoes barrierless ESIPT giving a QM via a conical intersection. However, due to an unfavorable conformation in the ground state, the quantum efficiency for ESIPT of 3 is significantly lower (Phi for D-exchange=0.041). These results show that ESIPT from phenol to carbon need not be an intrinsically inefficient process. PMID- 22782656 TI - Sequential methyl-fluorine exchange reactions of siloxide ions in the gas phase. AB - Exchange Me for a fluorine: Trimethylsiloxide ions in the presence of NF(3) in the gas phase undergo an unusual and sequential metathesis-type reaction wherein methyl groups are exchanged for fluorine. Theoretical calculations suggest that the reaction proceeds by a three-step internal-nucleophilic-displacement mechanism which features a pentacoordinated siliconate species as a transition state rather than as an intermediate. PMID- 22782657 TI - Reply: To PMID 22431471. PMID- 22782658 TI - [The living conditions of older people in Tanzania]. AB - Gerontology is not yet part of education or research in Tanzania. Descriptive analyses are valuable to determine the status quo of the living conditions of elderly people and thereby the basis for prospective gerontological discussions. The purpose of this article was to inquire about available data to describe the living conditions of old people in Tanzania, their problems, and potentials. Thereby, age definitions and the demographic development are examined and data sources from the Tanzanian statistical coverage, the SAGE pilot study as well as data from various research projects are discussed. The article closes with recommendations for a more extensive scientific analysis of the topic "Aging in Tanzania" as well as references for its implementation. PMID- 22782659 TI - [How municipalities can plan for later life. Regional challenges of a demography sensitive social planning for later life as exemplified by the administrative district Vechta (Lower Saxony/Germany)]. AB - The demographic ageing of the population confronts towns, municipalities and administrative districts with new sociopolitical challenges. The general view of the demographic and social change requires demography-sensitive social planning that is no longer segregated according to age or life stages. Drawing on the example of a demographic evaluation conducted for the administrative district of Vechta in Lower Saxony, Germany, it will be discussed how a life course orientated municipal social planning for later life can be developed. Furthermore, which practical research and methodical challenges the gerontological policy development municipalities can expect to be confronted with in the future are discussed. PMID- 22782660 TI - [Regional impact of German statutory pension insurance]. AB - The regional impact of old age pension systems has received little attention. For example, the German statutory pension insurance ("gesetzliche Rentenversicherung", GRV) was hitherto to the greatest extent discussed in the context with the situation in West and East Germany. However, the benefits of old age pension systems can have economic effects on the regional level. The article focuses on those aspects of the GRV: the economic relevance on the regional level is discussed, the quantitative importance is shown, and against this background some consequences of the reduction of the benefit level are problematized. The descriptive analysis illustrates the economic relevance of benefits of the GRV for regions in Germany. It contributes to regional purchasing power with manifold direct and indirect effects, which are different according to the regional characteristics. It is evident that the economy of regions with a low gross domestic product (GDP) to a great extent depends on the benefits of the GRV. The benefits are also relevant for the financial situation of the communities because they are preventing the occurrence of social problems or reducing their effects. The reduction of the level of the benefits implies income losses for private households, which affects communities to a different extent. Overall, the benefits of the GRV are of high relevance for the adaptation or the increase of the differences of the regional living conditions, e.g., between agglomeration and rural regions. PMID- 22782661 TI - The grapes of war. Somatoform pain disorder and history of early war traumatization in older people. AB - Persistent pain is not a normal part of aging. Nevertheless, many older patients have long-lasting, more or less medically unexplained pain symptoms and, consequently, are often severely disabled, incur high health care costs, and have high comorbidity rates. Moreover, the effects of early traumatization, especially due to wars, and even below the level of posttraumatic stress disorder (PTSD) are apparent. However, the developmental and neurobiological underpinnings of somatoform pain disorder, especially in pain-prone elderly patients, and its correlations with a history of war traumatization even decades after the incident remain unclear. Furthermore, a management strategy for this disorder tailored to older people and their special needs is lacking. Adequate therapeutic regimens such as adjusted psychotherapeutic procedures for elderly patients can only be promoted through a better understanding of the neurobiological and biographical underpinnings of this still controversial disorder. PMID- 22782668 TI - Evaluation of dynamic change of serum miR-21 and miR-24 in pre- and post operative lung carcinoma patients. AB - Although circulating microRNAs (miRNAs) were frequently detected in sera of cancer patients, there is still a lack of analysis of the dynamic changes of miRNAs expression in sera of pre- and post-operative lung carcinoma patients. Thus, we conducted quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to examine the expression of four miRNAs (miR-21, miR-205, miR-30d, and miR-24) in the sera of a set of 82 pre-operative lung carcinoma patients and paired 10 days post-operative patients, as well as in 50 normal volunteers. We showed that, compared to that in normal volunteers, the expression of miR-21, miR 205, miR-30d, and miR-24 was increased in lung cancer sera samples, as well as in sera of early stage lung cancer patients according to their clinical-pathological characteristics. The area under roc curves (AUCs) for levels of miR-21, miR-205, miR-30d, and miR-24 in sera were significantly higher than those for Carcinoma embryonic antigen (CEA) (P < 0.05), whereas the AUC for combination of serum levels of miRNA with serum CEA showed no significant difference from that for serum levels of miRNAs only (P > 0.05). The expression levels of miR-21 and miR 24 were significantly decreased in post-operative sera compared with levels in paired pre-operative sera (P = 0.0004 and <0.0001, respectively). In addition, high expressions of miR-21 and miR-30d in pre-operative sera were independently correlated with shorter overall survival in lung cancer patients (log-rank test: P = 0.0498, 0.0019). In summary, our results suggest that miR-21, miR-205, miR 30d, and miR-24 may serve as potential novel non-invasive biomarkers for diagnosis of lung cancer. In addition, miR-21 and miR-24 serum levels were lower in post-operative samples than those in pre-operative samples, suggesting they can potentially be used as biomarkers for disease recurrence after surgery operation. PMID- 22782667 TI - Quantitative mapping of total choline in healthy human breast using proton echo planar spectroscopic imaging (PEPSI) at 3 Tesla. AB - PURPOSE: To quantitatively measure tCho levels in healthy breasts using Proton Echo-Planar-Spectroscopic-Imaging (PEPSI). MATERIALS AND METHODS: The two dimensional mapping of tCho at 3 Tesla across an entire breast slice using PEPSI and a hybrid spectral quantification method based on LCModel fitting and integration of tCho using the fitted spectrum were developed. This method was validated in 19 healthy females and compared with single voxel spectroscopy (SVS) and with PRESS prelocalized conventional Magnetic Resonance Spectroscopic Imaging (MRSI) using identical voxel size (8 cc) and similar scan times (~7 min). RESULTS: A tCho peak with a signal to noise ratio larger than 2 was detected in 10 subjects using both PEPSI and SVS. The average tCho concentration in these subjects was 0.45 +/- 0.2 mmol/kg using PEPSI and 0.48 +/- 0.3 mmol/kg using SVS. Comparable results were obtained in two subjects using conventional MRSI. High lipid content in the spectra of nine tCho negative subjects was associated with spectral line broadening of more than 26 Hz, which made tCho detection impossible. Conventional MRSI with PRESS prelocalization in glandular tissue in two of these subjects yielded tCho concentrations comparable to PEPSI. CONCLUSION: The detection sensitivity of PEPSI is comparable to SVS and conventional PRESS-MRSI. PEPSI can be potentially used in the evaluation of tCho in breast cancer. A tCho threshold concentration value of ~0.7 mmol/kg might be used to differentiate between cancerous and healthy (or benign) breast tissues based on this work and previous studies. PMID- 22782669 TI - Loss of astrocyte polarization upon transient focal brain ischemia as a possible mechanism to counteract early edema formation. AB - Brain edema is the main cause of death from brain infarction. The polarized expression of the water channel protein aquaporin-4 (AQP4) on astroglial endfeet surrounding brain microvessels suggests a role in brain water balance. Loss of astrocyte foot process anchoring to the basement membrane (BM) accompanied by the loss of polarized localization of AQP4 to astrocytic endfeet has been shown to be associated with vasogenic/extracellular edema in neuroinflammation. Here, we asked if loss of astrocyte polarity is also observed in cytotoxic/intracellular edema following focal brain ischemia after transient middle cerebral artery occlusion (tMCAO). Upon mild focal brain ischemia, we observed diminished immunostaining for the BM components laminin alpha4, laminin alpha2, and the proteoglycan agrin, in the core of the lesion, but not in BMs in the surrounding penumbra. Staining for the astrocyte endfoot anchorage protein beta-dystroglycan (DG) was dramatically reduced in both the lesion core and the penumbra, and AQP4 and Kir4.1 showed a loss of polarized localization to astrocytic endfeet. Interestingly, we observed that mice deficient for agrin expression in the brain lack polarized localization of beta-DG and AQP4 at astrocytic endfeet and do not develop early cytotoxic/intracellular edema following tMCAO. Taken together, these data indicate that the binding of DG to agrin embedded in the subjacent BM promotes polarized localization of AQP4 to astrocyte endfeet. Reduced DG protein levels and redistribution of AQP4 as observed upon tMCAO might therefore counteract early edema formation and reflect a beneficial mechanism operating in the brain to minimize damage upon ischemia. PMID- 22782670 TI - Transition state theory thermal rate constants and RRKM-based branching ratios for the N((2)D) + CH(4) reaction based on multi-state and multi-reference ab initio calculations of interest for the Titan's chemistry. AB - Multireference single and double configuration interaction (MRCI) calculations including Davidson (+Q) or Pople (+P) corrections have been conducted in this work for the reactants, products, and extrema of the doublet ground state potential energy surface involved in the N((2)D) + CH(4) reaction. Such highly correlated ab initio calculations are then compared with previous PMP4, CCSD(T), W1, and DFT/B3LYP studies. Large relative differences are observed in particular for the transition state in the entrance channel resolving the disagreement between previous ab initio calculations. We confirm the existence of a small but positive potential barrier (3.86 +/- 0.84 kJ mol(-1) (MR-AQCC) and 3.89 kJ mol( 1) (MRCI+P)) in the entrance channel of the title reaction. The correlation is seen to change significantly the energetic position of the two minima and five saddle points of this system together with the dissociation channels but not their relative order. The influence of the electronic correlation into the energetic of the system is clearly demonstrated by the thermal rate constant evaluation and it temperature dependance by means of the transition state theory. Indeed, only MRCI values are able to reproduce the experimental rate constant of the title reaction and its behavior with temperature. Similarly, product branching ratios, evaluated by means of unimolecular RRKM theory, confirm the NH production of Umemoto et al., whereas previous works based on less accurate ab initio calculations failed. We confirm the previous findings that the N((2)D) + CH(4) reaction proceeds via an insertion-dissociation mechanism and that the dominant product channels are CH(2)NH + H and CH(3) + NH. PMID- 22782671 TI - A comparison of indocyanine green fluorescence imaging plus blue dye and blue dye alone for sentinel node navigation surgery in breast cancer patients. AB - PURPOSE: To evaluate two methods of sentinel node navigation surgery (SNNS) using blue dye with and without indocyanine green (ICG) fluorescence imaging (FI) to determine the usefulness of combined ICG and blue dye. METHODS: Between 2005 and 2010, a total of 501 patients underwent SNNS in our hospital. Detection of sentinel lymph node (SLN) was performed with sulfan blue (SB) alone until 2008 and with a combination of SB and ICG-FI since 2009. ICG 5 mg and SB 15 mg were injected in the subareolar region, and FI was obtained by a fluorescence imaging device. RESULTS: We attempted to identify SLNs in 393 patients by SB alone and in 108 patients by a combination of SB and FI. The mean number of SLNs detected was 1.6 (0-5) for SB alone and 2.2 (1-6) for the combination method. The SLN identification rate was 95.7 % for SB alone and 100 % for the combination method so that the combination was significantly superior to SB in terms of the identification rate (p = 0.0037). In patients who received the combination method, detection of SLN was made through only SB in 1 patient, only ICG in 8 patients, and both in 99 patients. Lymph node metastasis was found in 56 patients with SB alone and in 16 patients with the combination method. Recurrence of an axillary node was observed in 3 patients (0.8 %) with SB alone and in no patients with the combination method. CONCLUSIONS: ICG-FI is a useful method and is especially recommended in cases where no radiotracers are available. PMID- 22782685 TI - Positive argument for debate in J Neural Transmission: Alzheimer's disease: are we intervening too late? Yes, by years if not decades. AB - The ongoing debate as to whether we are or are not early enough in treatment for Alzheimer's disease presents distinct vantage points. Points expressed range from stressing the need for early preventive measures to highlighting the failure of "alternative" therapies, and concluding that we are unfortunately doing all that we can at present. Herein, we stress the worth of nutritional intervention, and review why such studies are often inherently compromised. We conclude that considerable education is needed to advance lifestyle modifications early enough to obtain their optimal effect, and instead of positioning "classical" interventions against "alternative" interventions, the combinations of both may impart maximal benefit. The introduction of novel detection methods at the earliest indications of cognitive impairment may provide a window of opportunity for initiation of preventative approaches. PMID- 22782686 TI - Meta-analysis of the transforming growth factor-beta1 polymorphisms and susceptibility to Alzheimer's disease. AB - The association between transforming growth factor-beta1 (TGF-beta1) gene polymorphisms and Alzheimer's disease (AD) risk has been widely reported, but results were somewhat controversial and underpowered. To derive a more precise estimation of the relationship between TGF-beta1 polymorphisms and AD risk, we conducted a meta-analysis of all available case-control studies relating the T869C and/or C-509T polymorphisms of the TGF-beta1 gene to the risk of developing AD. Eligible articles were identified by search of databases including Pub Med, Web of Science, the Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and the Wan Fang (Chinese) for the period up to March 2012. Finally, a total of 14 articles were identified, 10 with 1,657 cases and 6,971 controls for T869C polymorphism and 8 with 2,618 cases and 7,473 controls for C 509T polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model and recessive genetic model, respectively. Subgroup analysis was also performed by ethnicity. With respect to T869C and C-509T polymorphism, the combined results showed that there were no significant differences in genotype distribution between AD and control based on all studies. When stratifying for the race, there were also no statistically significant differences in genotype distribution between AD and controls. This meta-analysis did not provide an evidence of confirming association between the T869C and/or C-509T polymorphisms of the TGF-beta1 gene and AD. PMID- 22782688 TI - Gold-gold cooperation in the addition of methanol to alkynes. PMID- 22782687 TI - Different effects of soluble and aggregated amyloid beta42 on gene/protein expression and enzyme activity involved in insulin and APP pathways. AB - Although Alzheimer's dementia (AD) is not characterised any longer simply as the accumulation and deposition of amyloid beta (Abeta) peptides and hyperphosphorylation of tau proteins within the brain, excessive Abeta(42) deposition is still considered to play a major role in this illness. Abeta are able to adopt many differently aggregate forms, including amyloid fibrils as well as nonfibrillar structures (soluble Abeta(42) oligomers). It is not well established that which Abeta(42) state is most responsible for AD or why. We wanted to verify which effects Abeta(42) oligomers and aggregated peptides have on gene expression, protein level and enzyme activity of insulin and amyloid precursor protein (APP) pathways in vitro. Human neuroblastoma cells (SH-SY5Y) were treated with varying concentrations of soluble and aggregated Abeta(42). Treatment effects on beta-secretase (BACE), glycogen synthase kinase 3alpha (GSK3alpha), glycogen synthase kinase 3beta (GSK3beta), phosphatidylinositol-3 kinase (PI-3K), insulin-degrading enzyme (IDE), insulin-receptor substrate 1 (IRS1), insulin receptor (INSR) and monoamine oxidase B (MAO-B) were investigated via quantitative-PCR, western blot, ELISA and enzyme activity assay. We could find different effects of soluble and aggregated peptides especially on gene/protein expression of GSK3beta and INSR and on GSK3beta and MAO-B activity. Soluble peptides showed significant effects leading to increased gene expression and protein amount of GSK3beta and to decreased level of gene and protein expression of INSR. MAO-B activity was enhanced after treatment with aggregated peptides and strongly inhibited after soluble Abeta(42) treatment. Our data might provide insights into selective effects of specific forms of Abeta(42) aggregates in AD. PMID- 22782689 TI - Isolation, identification, and culture of goat spermatogonial stem cells using c kit and PGP9.5 markers. AB - INTRODUCTION: Presently the techniques for making transgenic animals are cumbersome, required costly instruments and trained man-power. The ability of spermatogonial stem cells (SSCs) to integrate foreign genes has provided the opportunity for developing alternate methods for generation of transgenic animals. One of the big challenges in this field is development of the methods to identify and purify donor SSCs by antibody mediated cell sorting. PURPOSE: The present study was aimed to identify goat subpopulations of SSCs using polyclonal antibodies against PGP9.5 and c-kit molecular markers as well as the growth characteristics of SSCs during short term culture. METHODS: One month old goats' testicular samples were subjected for immunohistochemical and immunocytochemical evaluations. The enzymatically isolated SSCs were cultured in DMEM plus FCS supplemented with (treatment) or without (control) growth factors (GDNF, LIF, FGF, and EGF) for 2 weeks. At the end of culture the morphological characteristics of SSCs colonies and immunocytochemical staining were evaluated. RESULTS: The number and size of colonies in treatment groups were significantly (P < 0.01) higher than corresponding values in controls. The presence of PGP 9.5 and c-kit antigens was confirmed in immunocytochemical evaluation. In immunocytochemical evaluation, the proportion of c-kit and PGP9.5 positive cells were significantly (P < 0.001) higher in control and treatment groups, respectively. CONCLUSIONS: The presence of PGP9.5 and c-kit antigens was confirmed in goat SSCs. Moreover, culture medium supplementation with growth factors could effectively retain the undifferentiation status of SSCs, reflected as a higher population of PGP9.5 positive cells, after short term culture. PMID- 22782690 TI - Mapping of the PDQ-39 to EQ-5D scores in patients with Parkinson's disease. AB - PURPOSE: The EuroQoL (EQ-5D) is ideal to compare quality of life across conditions. However, the Parkinson's Disease Questionnaire (PDQ-39) is often the only quality-of-life instrument used in Parkinson's disease research. We aimed to identify associations between PDQ-39 domains and EQ-5D domains, and compare different methods of developing a function to map the PDQ-39 to EQ-5D scores. METHODS: Adults with Parkinson's disease self-completed both instruments. Ordinal regression identified associations between PDQ-39 domain scores and each EQ-5D domain. Modeling (n = 80) and validation sets (n = 16) were randomly generated. Overall performance of four methods of mapping the PDQ-39 to EQ-5D scores (using PDQ-39 domains and total score in ordinal and linear regression) was assessed with the validation set, followed by assessing the equivalence of observed and predicted EQ-5D scores on the full dataset controlling for sociodemographic factors. RESULTS: Different sets of PDQ-39 domains were associated with each EQ 5D domain. For example, PDQ-39 "Activities of Daily Living" and "Social Support" were associated with EQ-5D "Personal Care," while PDQ-39 "Emotional Well-being" was associated with EQ-5D "Anxiety/Depression." Over one-third (37.5 %) of predictions from ordinal regressions had an error <0.01 % (compared to 6.3 % for linear regressions). The EQ-5D scores predicted with ordinal regression using PDQ 39 domains were similar in distribution and association with sociodemographic factors to the observed EQ-5D scores. CONCLUSIONS: Of the four methods tested, using PDQ-39 domains in ordinal regression was superior for mapping EQ-5D scores. The function reported here may prove particularly useful for cost-utility analyses comparing Parkinson's disease with other conditions. PMID- 22782691 TI - Analysis of pulsed laser plasmon-assisted photothermal heating and bubble generation at the nanoscale. AB - A study is presented of photothermal effects associated with nanosecond-pulsed laser-illuminated subwavelength metallic nanoparticles in aqueous solutions. Computational electromagnetic and fluid analysis are used to model fundamental aspects of the photothermal process taking into account energy conversion within the nanoparticle at plasmon resonance, heat transfer to the fluid, homogeneous bubble nucleation, and the dynamic behaviour of the bubble and surrounding fluid. Various nanoparticle geometries are modelled including spheres, nanorods and tori. The analysis demonstrates that the laser intensity and pulse duration can be tuned to achieve controllable bubble generation without exceeding the melting temperature of the particle. The analysis also shows that the particle geometry can be tuned to optimize photothermal energy conversion for bubble generation at wavelengths that span the UV to NIR spectrum. Multiparticle systems are studied and a cooperative heating effect is demonstrated for particles that are within a few radii of each other. This provides more robust bubble generation using substantially reduced laser energy as compared to single-particle systems. The modelling approach is discussed in detail and should be of considerable use in the development of new photothermal applications. PMID- 22782692 TI - Interleukin-33 is hepatoprotective during liver ischemia/reperfusion in mice. AB - Interleukin (IL)-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. In the current study, we sought to determine whether IL-33 is an important regulator in the hepatic response to ischemia/reperfusion (I/R). Male C57BL/6 mice were subjected to 90 minutes of partial hepatic ischemia, followed by up to 8 hours of reperfusion. Some mice received recombinant IL-33 (IL-33) intraperitoneally (IP) before surgery or anti-ST2 antibody IP at the time of reperfusion. Primary hepatocytes and Kupffer cells were isolated and treated with IL-33 to assess the effects of IL-33 on inflammatory cytokine production. Primary hepatocytes were treated with IL-33 to assess the effects of IL-33 on mediators of cell survival in hepatocytes. IL-33 protein expression increased within 4 hours after reperfusion and remained elevated for up to 8 hours. ST2L protein expression was detected in healthy liver and was up-regulated within 1 hour and peaked at 4 hours after I/R. ST2L was primarily expressed by hepatocytes, with little to no expression by Kupffer cells. IL-33 significantly reduced hepatocellular injury and liver neutrophil accumulation at 1 and 8 hours after reperfusion. In addition, IL-33 treatment increased liver activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-kappaB), p38 mitogen-activated protein kinase (MAPK), cyclin D1, and B-cell lymphoma 2 (Bcl 2), but reduced serum levels of CXC chemokines. In vitro experiments demonstrated that IL-33 significantly reduced hepatocyte cell death as a result of increased NF-kappaB activation and Bcl-2 expression in hepatocytes. CONCLUSION: The data suggest that IL-33 is an important endogenous regulator of hepatic I/R injury. It appears that IL-33 has direct protective effects on hepatocytes, associated with the activation of NF-kappaB, p38 MAPK, cyclin D1, and Bcl-2 that limits liver injury and reduces the stimulus for inflammation. PMID- 22782693 TI - Distribution of procyanidins and their metabolites in rat plasma and tissues in relation to ingestion of procyanidin-enriched or procyanidin-rich cocoa creams. AB - BACKGROUND: Procyanidins are extensively metabolized via phase-II and microbial enzymes. However, their distribution in the body is not well characterized. AIM: This study investigates the distribution of procyanidins (monomers and dimers) and their phase-II metabolites in plasma and tissues (thymus, heart, liver, testicle, lung, kidney, spleen and brain). METHODS: Wistar rats were fed with 1 g of cocoa cream (CC), 50 mg of procyanidin hazelnut skin extract (PE) and 50 mg PE in 1 g CC (PECC). The rats were killed at 0, 1, 1.5, 2, 3, 4 and 18 h after gavage, and the plasma and tissues were analyzed by UPLC-MS/MS. RESULTS: Epicatechin-glucuronide was the main metabolite in the plasma after the CC intake, with C(max) at 423 nM and t(max) at 2 h, and methyl catechin-glucuronide (301 nM, 2 h) was the main metabolite in the plasma after the PE intake. As a result of the PECC enrichment, epicatechin-glucuronide (452 nM, 1.5 h) and catechin-glucuronide (297 nM, 2 h) were the main metabolites in the plasma. Methyl catechin-glucuronide was found in the liver after PE (8 nmol/g tissue, 4 h) and PECC (8 nmol/g, 1.5 h). The kidney was found to contain a high concentration of phase-II metabolites of procyanidins and is therefore thought to be the main site of metabolism of the compounds. Methyl catechin-sulfate (6.4 nmol/g, 4 h) was only quantified in the brain and after PE intake. Catechin metabolites were not found in the spleen or heart. Phenolic acids were detected in all tissues. CONCLUSIONS: The formulation of a product enriched or fortified with procyanidins is a way to increase their bioavailability, with clear effects on the plasmatic pharmacokinetics, and a greater accumulation of phenolic metabolites in such tissues as the liver, kidney, lung and brain. PMID- 22782694 TI - MRSA decolonization: success rate, risk factors for failure and optimal duration of follow-up. AB - PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) decolonization is a widely established, though controversial part of many MRSA controlling strategies. The aim of this study was to evaluate our decolonization success rate, identify the risk factors for decolonization failure and determine the optimal duration of follow-up in our low MRSA prevalence setting (2.6 % of isolates). METHODS: Every patient with newly detected MRSA colonization or infection between January 2007 and December 2009 was recruited to the study. The MRSA strategy of our institution (a 700 bed tertiary hospital in eastern Switzerland) consists of a 5-day regimen of nasal mupirocin ointment, chlorhexidin mouth rinse and whole body wash with didecyldimonium chloride. Systemic antibiotics are usually not added to the regimen. RESULTS: We determined a MRSA decolonization success rate of 65 % (33/51) after a median follow-up of 13 months [i.e. a tripling of the spontaneous clearance rate of 22 % (6/27) in the non-decolonized group]. The most important risk factor for decolonization failure was colonization of the respiratory tract [odds risk (OR) 9.1, 95 % confidence interval (CI) 1.2-66.7], as well as isolation of MRSA spa-type 002 ([R 5.8, 95 % CI 1.0-33.3). Of all the episodes of MRSA recurrence, 88 % (14/16) were detected within 270 days after decolonization. CONCLUSION: High MRSA decolonization success rates can be achieved without the routine use of oral antibiotics. A time period of 1 year after decolonization seems to be a reasonable duration of follow up in our setting. We encourage other institutions to take into account local MRSA epidemiology (e.g. predominance of certain subtypes) for the management of MRSA patients. PMID- 22782695 TI - Aseptic meningitis and adult respiratory distress syndrome caused by Borrelia persica. AB - INTRODUCTION: The occurrence of some of the clinical complications of tickborne relapsing fever varies with Borrelia species. For example, adult respiratory distress syndrome (ARDS), a newly reported complication, was described so far only with B. hermsii infection. MATERIALS AND METHODS: A previously healthy young Israeli man was admitted for fever and headache and was diagnosed as aseptic meningitis. Shortly before the lumbar puncture was performed he started to experience shortness of breath and developed acute respiratory insufficiency necessitating mechanical ventilation. Radiography, which was normal on admission, demonstrated bilateral lung infiltrates consistent with ARDS. Spirochetes suggestive of Borrelia were seen on a thick blood smear preparation, and polymerase chain reaction was positive for B. persica. CONCLUSION: This is the first reported case of ARDS in association with Borrelia spp. occurring outside the U.S.A. and the first one due to B. persica infection. PMID- 22782696 TI - Activation and coordination of ammonia at [Cp*Ir(H)2]: NMR and matrix isolation studies. AB - (1)H NMR exchange spectroscopy of a reaction mixture of [Cp*Ir(H)(4)] (1; Cp*=1,2,3,4,5-pentamethylcyclopentadienyl) and ammonia suggests an exchange of hydrogen atoms between the hydrido ligands and ammonia. Treatment of 1 with ND(3) led to an H/D exchange between ND(3) and the hydrido ligands of 1. Subsequent studies showed that photolysis of 1 isolated in frozen argon matrices leads to the formation of the iridium compounds [Cp*Ir(H)(2)] (2) and [Cp*Ir(H)(3)] (4), as it was confirmed by IR spectroscopy. In the presence of water the aqua complex [Cp*Ir(H)(2)(OH(2))] (3) was generated simultaneously. Accordingly, photolysis of 1 in an argon matrix doped with ammonia gave rise to the ammine complex [Cp*Ir(H)(2)(NH(3))] (5). IR assignments were supported by calculations of the gas-phase IR spectra of 1-5 by DFT methods. PMID- 22782697 TI - Synthesis and structural characterization of new divanada- and diniobaboranes containing chalcogen atoms. AB - The reaction of [Cp(n)MCl(4-x)] (M=V: n=2, x=2; M=Nb: n=1, x=0; Cp=eta(5)-C(5) H(5)) with LiBH(4)?THF followed by thermolysis in the presence of dichalcogenide ligands E(2)R(2) (E=S, Te; R=2,6-(tBu)(2)-C(6)H(2)OH, Ph) and 2 mercaptobenzothiazole (C(7)H(5)NS(2)) yielded dimetallaheteroboranes [{CpV(MU TePh)}(2)(MU(3) -Te)BH?thf] (1), [(CpV)(2)(BH(3)S)(2)] (2), [(CpNb)(2)B(4)H(10)S] (3), [(CpNb)(2)B(4)H(11)S(tBu)(2)C(6)H(2)OH] (4), and [(CpNb)(2)B(4)H(11)TePh] (5). In cluster 1, the V(2)BTe atoms define a tetrahedral framework in which the boron atom is linked to a THF molecule. Compound 2 can be described as a dimetallathiaborane that is built from two edge-fused V(2)BS tetrahedron clusters. Cluster 3 can be considered as an edge-fused cluster in which a trigonal-bipyramidal unit (Nb(2)B(2)S) has been fused with a tetrahedral core (Nb(2)B(2)) by means of a common Nb(2) edge. In addition, thermolysis of an in situ-generated intermediate that was produced from the reaction of [Cp(2)VCl(2)] and LiBH(4)?THF with excess BH(3)?THF yielded oxavanadaborane [(CpV)(2)B(3)H(8)(MU(3)-OEt)] (6) and divanadaborane cluster [(CpV)(2)B(5)H(11)] (7). Cluster 7 exhibits a nido geometry with C(2v) symmetry and it is isostructural with [(Cp*M)(2)B(5)H(9+n)] (M=Cr, Mo, and W, n=0; M=Ta, n=2; Cp*=eta(5)-C(5)Me(5)). All of these new compounds have been characterized by (1)H NMR, (11)B NMR, and (13)C NMR spectroscopy and elemental analysis and the structural types were established unequivocally by crystallographic analysis of compounds 1-4, 6, and 7. PMID- 22782698 TI - Measuring bone mineral density with fat-water MRI: comparison with computed tomography. AB - PURPOSE: To develop a method for measuring bone mineral density (BMD) with MRI, and to validate this method against quantitative computed tomography (QCT). MATERIALS AND METHODS: A mathematical relationship between signal intensities from proton-density-weighted in-phase images generated by multi-fat-peak T2* IDEAL MRI and BMD was derived using a set of calibration standards constructed from various concentrations of hydroxyapatite in water. Using these standards, the relationship between hydroxyapatite concentration and MRI signal intensity was examined. A T2*-IDEAL protocol was performed on the patella of 5 volunteers and the signal model was used to compute BMD of all voxels of the patella. The BMD data were validated by obtaining QCT scans of the same patella, computing QCT BMD of all voxels, and comparing the MRI and QCT BMD data by performing linear regression analysis on a voxel-by-voxel basis. RESULTS: A strong linear correlation between hydroxyapatite concentration of the calibration standards and MRI signal intensities was observed (r = 0.98; P < 0.01). In the patella, BMD measurements (N = 28796 voxels) from the MRI signal model were significantly correlated with those from QCT (r = 0.82; P < 0.001; slope = 1.02; and intercept = -0.26). CONCLUSION: A standardized phantom consisting of hydroxyapatite and water can be used to accurately quantify BMD in vivo using MRI. PMID- 22782699 TI - Evolution of gene expression changes in newborn rats after mechanical ventilation with reversible intubation. AB - Mechanical ventilation (MV) is life-saving but potentially harmful for lungs of premature infants. So far, animal models dealt with the acute impact of MV on immature lungs, but less with its delayed effects. We used a newborn rodent model including non-surgical and therefore reversible intubation with moderate ventilation and hypothesized that there might be distinct gene expression patterns after a ventilation-free recovery period compared to acute effects directly after MV. Newborn rat pups were subjected to 8 hr of MV with 60% oxygen (O(2)), 24 hr after injection of lipopolysaccharide (LPS), intended to create a low inflammatory background as often recognized in preterm infants. Animals were separated in controls (CTRL), LPS injection (LPS), or full intervention with LPS and MV with 60% O(2) (LPS + MV + O(2)). Lungs were recovered either directly following (T:0 hr) or 48 hr after MV (T:48 hr). Histologically, signs of ventilator-induced lung injury (VILI) were observed in LPS + MV + O(2) lungs at T:0 hr, while changes appeared similar to those known from patients with chronic lung disease (CLD) with fewer albeit larger gas exchange units, at T:48 hr. At T:0 hr, LPS + MV + O(2) increased gene expression of pro-inflammatory MIP-2. In parallel anti-inflammatory IL-1Ra gene expression was increased in LPS and LPS + MV + O(2) groups. At T:48 hr, pro- and anti-inflammatory genes had returned to their basal expression. MMP-2 gene expression was decreased in LPS and LPS + MV + O(2) groups at T:0 hr, but no longer at T:48 hr. MMP-9 gene expression levels were unchanged directly after MV. However, at T:48 hr, gene and protein expression increased in LPS + MV + O(2) group. In conclusion, this study demonstrates the feasibility of delayed outcome measurements after a ventilation free period in newborn rats and may help to further understand the time-course of molecular changes following MV. The differences obtained from the two time points could be interpreted as an initial transitory increase of inflammation and a delayed impact of the intervention on structure-related genes. PMID- 22782700 TI - Evaluating nonpolarizable nucleic acid force fields: a systematic comparison of the nucleobases hydration free energies and chloroform-to-water partition coefficients. AB - Nucleic acid force fields have been shown to reproduce structural properties of DNA and RNA very well, but comparative studies with respect to thermodynamic properties are rare. As a test for thermodynamic properties, we have computed hydration free energies and chloroform-to-water partition coefficients of nucleobases using the AMBER-99, AMBER-gaff, CHARMM-27, GROMOS-45a4/53a6 and OPLS AA force fields. A mutual force field comparison showed a very large spread in the calculated thermodynamic properties, demonstrating that some of the parameter sets require further optimization. The choice of solvent model used in the simulation does not have a significant effect on the results. Comparing the hydration free energies obtained by the various force fields to the adenine and thymine experimental values showed a very large deviation for the GROMOS and AMBER parameter sets. Validation against experimental partition coefficients showed good agreement for the CHARMM-27 parameter set. In view of mutation studies, differences in partition coefficient between two bases were also compared, and good agreement between experiments and calculations was found for the AMBER-99 parameter set. Overall, the CHARMM-27 parameter set performs best with respect to the thermodynamic properties tested here. PMID- 22782701 TI - Improved growth, drought tolerance, and ultrastructural evidence of increased turgidity in tobacco plants overexpressing Arabidopsis vacuolar pyrophosphatase (AVP1). AB - An increasing volume of evidence indicating the mechanisms of drought tolerance of AVP1-overexpressing transgenic plants has been reported. In the present study, we are reporting the experiments conducted for the drought tolerance of AVP1 overexpressing plants and WT tobacco plants in three water regimes named as "fully watered," "less-watered," and "desiccated". Results suggest that AVP1 plants exhibited greater vigor and drought tolerance in quantitative terms i.e., increase in size and weight of shoots and capsules. AVP1 plants produced more seeds than WT across all three water regimes. The less-watered regime was found to produce the greatest contrast. AVP1 overexpression enhanced solute accumulation in vacuoles resulting in an increase in water retention and turgor of the cell. The ultrastructure study of AVP1 overexpressing cells and WT leaf cells revealed that AVP1 plants displayed more turgid and hyperosmotic cells than WT. Moreover, guard cells in the AVP1 plants exhibited thick cell walls, few vacuoles, and deep and close stomata, whereas WT plants showed larger vacuoles and relatively open stomata aperture with no significant difference in size and number of the cells per unit area. PMID- 22782702 TI - Anatomical and physiological differences and differentially expressed genes between the green and yellow leaf tissue in a variegated chrysanthemum variety. AB - The leaves of the chrysanthemum variety 'NAU04-1-31-1' are variegated with distinct green and yellow sectors. The chlorophyll content of the yellow leaf tissue is less than that in the green one. The chloroplasts in the yellow leaf tissue were vacuolated, lacked thylakoid membrane structure and contained clusters of plastoglobuli with few or no starch grains. The yellow leaf tissue was more sensitive to photo-inhibition than the green leaf tissue. Suppression subtractive hybridization (SSHs) libraries were constructed to identify genes which were differentially transcribed in the two tissue types. The sequencing of 339 SSH clones identified 150 unigenes (93 singletons and 57 contigs), of which 85 were differentially transcribed in the green leaf tissue and 65 in the yellow leaf tissue. Unigenes associated with photosynthesis were particularly frequent, and many of these genes were up-regulated in the yellow leaf tissue. Both CmChlH which encodes the large subunit of Mg-chelatase and CmFtsH (ATP-dependent metalloprotease) were up-regulated in the yellow leaf tissue, and their transcription was regulated by light. PMID- 22782703 TI - A novel dual vector coexpressing PhiX174 lysis E gene and staphylococcal nuclease A gene on the basis of lambda promoter pR and pL, respectively. AB - Bacterial ghost is a novel vaccine platform, and its safe and efficient production depends largely upon a suitable and functional vector. In this study, a series of temperature-inducible plasmids, carrying Phix174 lysis gene E and/or staphylococcal nuclease A (SNA) gene, were constructed and evaluated in Escherichia coli. The results showed that the direct product of SNA (pBV220-SNA) could degrade the plasmid and genomic DNA of E. coli while the fusion product of gene E and partial Cro gene (pKF396M-2) lost the ability to lyse the host strain. The insertion of enhancer T7g10 elements and Shine-Dalgarno box (ESD) between them (pKF396M-3) could resume the function of gene E. Using plasmid pKF396M-4 with gene E and SNA, respectively, under the immediate control of promoter pR and pL, the remnant plasmids and genomic DNA of E. coli were eliminated, and the rates of inactivation increased by two orders of magnitude over that obtained with the exclusive use of E-mediated lysis plasmid. By substituting these two genes with customized multiple cloning sites sequences, the plasmid could be modified to a dual expression vector (pKF396M-5). PMID- 22782704 TI - An epidermal growth factor motif from Del1 protein increases the efficiency of in vivo gene transfer with a non-viral vector. AB - Increasing the efficiency of gene transfer using non-viral vectors, which have the potential to be safe and economical, would improve upon available options for gene therapy. We previously reported that the third EGF motif of the extracellular matrix protein Del1 (E3) increases the transfection efficiency of non-viral vector methods. Here, we asked if E3 could increase the in vivo transfection efficiency of a polyplex-based approach. To test this, cDNA encoding a heat-stable alkaline phosphatase (AP) was first injected intravenously into mice along with recombinant E3. After 24 h, exogenous AP activity in serum was measured. We found that the introduction of E3 resulted in 50 % more AP activity as compared to the control. We next tested transfection into a tumour explant of SCCKN cells, an oral carcinoma-derived cell line. To do this, a cDNA encoding yellow fluorescent protein was locally injected into a tumour explant, followed by local injection of recombinant E3. Use of E3 increased the number of transfected cells to 2.5 times that of the control. Histochemical staining revealed that E3-induced apoptosis in a tumour explant. The data suggest that E3 might be a useful tool for cancer gene therapy using non-viral vectors. PMID- 22782705 TI - Circulating miRNAs might be promising biomarkers to reflect the dynamic pathological changes in smoking-related interstitial fibrosis. AB - Cigarette smoking is the major risk factor for smoking-related interstitial fibrosis (SRIF). Despite recent advances, the molecular mechanisms involved in the initiation and progression of this disease remain elusive. We found 6 months of chronic mainstream smoking exposure induced SRIF in C57 mice, which was associated with pronounced enhanced oxidative stress, bronchoalveolar inflammation and fibrosis but not apoptosis of alveolar septal cell. We used Affymetrix microRNA (miRNA) arrays to determine the temporal alteration in global gene expression of peripheral blood during the progression of diffuse pulmonary interstitial fibrosis in C57 mice. Microarray analysis revealed the upregulation of 3 miRNAs (miR-92b, miR-700 and miR-668) and the downregulation of 5 miRNAs (let-7e, miR-142-5p, miR-350, miR-19a and miR191*) in the peripheral blood of mice exposed to mainstream smoking for 1, 2, 3 and 6 months. We proposed that circulating miRNAs might be promising biomarkers to reflect the dynamic pathological changes of SRIF related interstitial fibrosis. PMID- 22782706 TI - Mercury and arsenic in green tiger shrimp from the Persian Gulf. AB - Mercury and arsenic pollution has been recognized as a potential environmental and public health problem for over 40 years. The major source of exposure to mercury and arsenic for humans is the ingestion of sea food. Concentrations of mercury and arsenic in the muscle samples of green tiger shrimp (Penaeus semisulcatus) from the Persian Gulf were determined by cold vapor atomic absorption spectrometry. Concentrations of metals in muscle samples were 49-115 ug kg(-1) for mercury, 115-131 ug kg(-1)for arsenic, with means of 82.7 and 251.6 ug kg(-1), respectively. Statistical analysis showed no significant difference of mercury and arsenic concentration in shrimp muscles between selected stations (Bushehr, Khuzestan, and Hormozgan provinces). No significant difference was found among heavy metal contents of male and female shrimps. The results of this study indicate that the green tiger shrimp from the Persian Gulf have concentrations well below the maximum permissible levels for mercury (500 ug kg( 1)) and arsenic (6000 ug kg(-1)), according to international standards, with no health risk of consumers. PMID- 22782707 TI - Effect of aqueous extract of Crocus sativus L. (saffron) stigma against subacute effect of diazinon on specific biomarkers in rats. AB - In this study, the effect of aqueous extract of Crocus sativus L. (saffron) stigma was studied against subacute toxicity of diazinon (DZN) on specific biochemical markers in rats. Vitamin E (200 IU/kg) and the aqueous extract of saffron at doses 50, 100 and 200 mg/kg were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. Red blood cell (RBC) cholinesterase activity was inhibited by DZN and this effect was not affected by vitamin E or saffron plus DZN. The levels of serum tumor necrosis factor-alpha (inflammation marker), direct 8-iso-prostaglandin F(2alpha) (oxidative stress marker) and soluble protein-100 beta (S100beta, neuronal damage marker) were increased significantly by DZN. The saffron extract inhibited the effect of DZN on these biomarkers levels. However, vitamin E was able to only reduce 8-iso-prostaglandin F(2alpha) and S100beta levels. This study showed that the aqueous extract of saffron prevents DZN-induced rise of several specific inflammation, oxidative stress and neuronal damage biomarkers. PMID- 22782708 TI - Effects of bisphenol A on the development of central immune organs of specific pathogen-free chick embryos. AB - Bisphenol A (BPA) is a chemical estrogen widely used in the food packaging industry, especially in baby bottles. Its toxicity for the fetus has become a great concern in recent years. In the present study, the effects of BPA on the development of central immune organs in chick embryos were investigated. A total of 30 specific-pathogen-free (SPF) chick embryos were divided into BPA, control, and vehicle group. Chick embryos were exposed to BPA (250 MUg per egg), saline (control), or corn oil (vehicle) on embryonic day 9 (ED9) by injection into the allantoic cavity. Thymuses and bursae of Fabricius were collected on ED22. The microscopic examination of tissue structure and ultrastructure was carried out for histopathological changes of thymus and the bursa of Fabricius morphology under light and scanning electron microscopes (SEM). In the BPA group, the weight index of the bursae of Fabricius was significantly reduced (p < 0.01); the number of lymphatic follicles in the bursae of Fabricius was remarkably decreased (p < 0.01); and the thickness of the thymus cortex and medulla was reduced (p < 0.01). Light microscope and SEM examinations further showed that the lymphatic follicles and epithelial cells of the bursa of Fabricius and thymus were damaged by BPA. Our study confirms a direct toxicity of BPA at a very low-dose level on the development of the central immune organs of SPF chick embryos. However, more studies are necessary to elucidate the underlying mechanisms. PMID- 22782709 TI - The effect of supplementation of calcium, vitamin D, boron, and increased fluoride intake on bone mechanical properties and metabolic hormones in rat. AB - Evidence indicates that optimal nutrition plays a role in bone formation and maintenance. Besides major components of mineralization such as calcium, phosphorus, and vitamin D, other nutrients like boron and fluoride have beneficial role, too. In this study, 34 male Wistar rats were divided into five groups: control diet, fluoride, fluoride + boron, fluoride + calcium + vitamin D, and fluoride + boron + calcium + vitamin D. Boron equal to 1.23 mg, calcium and vitamin D equal to 210 mg + 55 IU and fluoride equal to 0.7 mg/rat/day was added to their drinking water for 8 weeks. Plasma blood samples and bones were collected. Findings are evidence that fluoride + boron intake revealed significant positive effects on bone mechanical properties and bone metabolic hormones. These findings suggest that combined intake of these two elements has beneficial effects on bone stiffness and breaking strength comparing to even calcium + vitamin D supplementation. This evidence dealing with health problems related to bone and skeletal system in humans should justify further investigation of the role of boron and fluoride with other elements in relation to bone. PMID- 22782710 TI - Effect of nanosilver on blood parameters in chickens having aflatoxicosis. AB - This experiment is designed to investigate the positive effects of commercial nanosilver compound on blood parameters in experimental aflatoxicosis in broiler chickens. For this, 270 one-day-old broiler chickens were randomly divided into six treatment groups with three replicates. The experimental groups were group A: chickens fed with basal diet; group B: chickens fed with 3 ppm productive aflatoxin in basal diet; groups of C, D, E and F received Mycoad (2.5 g/kg diet), Mycoad (2.5 g/kg diet) + productive aflatoxin (3 ppm), Nanocid (2500 ppm), and Nanocid (2500 ppm) + productive aflatoxin (3 ppm) in basal diet, respectively. Results revealed that some of the blood parameters such as mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration lymphocytes, neutrophils, basophils, monocytes, and eosinophils percentage were not affected in this experiment; whereas, hemoglobin percentage and white blood cell (WBC) count in all the groups fed with 3 ppm aflatoxin except nanocid + aflatoxin decreased significantly (p < 0.05). There are no significant differences between the groups that received nanocid + aflatoxin and mycoad + aflatoxin in hemoglobin percentage and WBC count parameters. The red blood cell count and hematocrit in chickens received aflatoxin were significantly lower than other groups (p < 0.05). Therefore, this study suggests that nanocid similar as mycoad can be useful in reducing the adverse effects of aflatoxin on blood parameters in chickens affected with aflatoxicosis. PMID- 22782711 TI - Recent progress of core-substituted naphthalenediimides: highlights from 2010. AB - Core-substituted naphthalenediimides (cNDIs) are rapidly emerging as a powerful strategy to create functional nanomaterials and their implications in biological and supramolecular chemistry are significant. Recent developments in the synthesis of cNDIs have allowed several groups to probe the function of this interesting class of dye molecules in a molecular and supramolecular sense. Core substitution of the NDI can be seen as an opportunity to extend the planar, rigid core and could be used to prepare novel structures for applications in organic, biosupramolecular chemistry, biomedicine, materials science and organic solar cells. In this Emerging Area, we provide up-to-date recent progress in the field of cNDIs. We begin with a general discussion and the applications of cNDIs in the field of supramolecular chemistry i.e. generation of nanostructures such as vesicles and nanotubes etc., and we also discuss advances in artificial photosynthesis. Following this is a section on their implications in the field of sensors, particularly DNA intercalation, anion sensing and NDI based pH sensors. Finally, we explore the recent development of cNDIs in organic solar cell applications. We conclude with our views on the prospects of cNDIs in future research. PMID- 22782712 TI - Copper-catalyzed aerobic dehydrogenative cyclization of N-methyl-N phenylhydrazones: synthesis of cinnolines. PMID- 22782716 TI - Computer-assisted study on the reaction between pyruvate and ylide in the pathway leading to lactyl-ThDP. AB - In this study the formation of the lactyl-thiamin diphosphate intermediate (L ThDP) is addressed using density functional theory calculations at X3LYP/6 31++G(d,p) level of theory. The study includes potential energy surface scans, transition state search, and intrinsic reaction coordinate calculations. Reactivity is analyzed in terms of Fukui functions. The results allow to conclude that the reaction leading to the formation of L-ThDP occurs via a concerted mechanism, and during the nucleophilic attack on the pyruvate molecule, the ylide is in its AP form. The calculated activation barrier for the reaction is 19.2 kcal/mol, in agreement with the experimental reported value. PMID- 22782717 TI - Evolutionary crossroads in developmental biology. PMID- 22782718 TI - Toward a blueprint for regeneration. AB - Tissue regeneration has been studied for hundreds of years, yet remains one of the less understood topics in developmental biology. The recent Keystone Symposium on Mechanisms of Whole Organ Regeneration brought together biologists, clinicians and bioengineers representing an impressive breadth of model systems and perspectives. Members of the growing regeneration community discussed classic and new ideas on mechanisms of regeneration and how these can be applied to regenerative medicine. PMID- 22782719 TI - Evolutionary crossroads in developmental biology: annelids. AB - Annelids (the segmented worms) have a long history in studies of animal developmental biology, particularly with regards to their cleavage patterns during early development and their neurobiology. With the relatively recent reorganisation of the phylogeny of the animal kingdom, and the distinction of the super-phyla Ecdysozoa and Lophotrochozoa, an extra stimulus for studying this phylum has arisen. As one of the major phyla within Lophotrochozoa, Annelida are playing an important role in deducing the developmental biology of the last common ancestor of the protostomes and deuterostomes, an animal from which >98% of all described animal species evolved. PMID- 22782720 TI - Evolutionary crossroads in developmental biology: the spider Parasteatoda tepidariorum. AB - Spiders belong to the chelicerates, which is an arthropod group that branches basally from myriapods, crustaceans and insects. Spiders are thus useful models with which to investigate whether aspects of development are ancestral or derived with respect to the arthropod common ancestor. Moreover, they serve as an important reference point for comparison with the development of other metazoans. Therefore, studies of spider development have made a major contribution to advancing our understanding of the evolution of development. Much of this knowledge has come from studies of the common house spider, Parasteatoda tepidariorum. Here, we describe how the growing number of experimental tools and resources available to study Parasteatoda development have provided novel insights into the evolution of developmental regulation and have furthered our understanding of metazoan body plan evolution. PMID- 22782721 TI - Genome-wide analysis reveals that Smad3 and JMJD3 HDM co-activate the neural developmental program. AB - Neural development requires crosstalk between signaling pathways and chromatin. In this study, we demonstrate that neurogenesis is promoted by an interplay between the TGFbeta pathway and the H3K27me3 histone demethylase (HDM) JMJD3. Genome-wide analysis showed that JMJD3 is targeted to gene promoters by Smad3 in neural stem cells (NSCs) and is essential to activate TGFbeta-responsive genes. In vivo experiments in chick spinal cord revealed that the generation of neurons promoted by Smad3 is dependent on JMJD3 HDM activity. Overall, these findings indicate that JMJD3 function is required for the TGFbeta developmental program to proceed. PMID- 22782722 TI - Zebrafish Cxcr4a determines the proliferative response to Hedgehog signalling. AB - The Hedgehog (Hh) pathway plays dual roles in proliferation and patterning during embryonic development, but the mechanism(s) that distinguish the mitogenic and patterning activities of Hh signalling are not fully understood. An additional level of complexity is provided by the observation that Hh signalling can both promote and inhibit cell proliferation. One model to account for this apparent paradox is that Hh signalling primarily regulates cell cycle kinetics, such that activation of Hh signalling promotes fast cycling and an earlier cell cycle exit. Here we report that activation of Hh signalling promotes endodermal cell proliferation but inhibits proliferation in neighbouring non-endodermal cells, suggesting that the cell cycle kinetics model is insufficient to account for the opposing proliferative responses to Hh signalling. We show that expression of the chemokine receptor Cxcr4a is a critical parameter that determines the proliferative response to Hh signalling, and that loss of Cxcr4a function attenuates the transcription of cell cycle regulator targets of Hh signalling without affecting general transcriptional targets. We show that Cxcr4a inhibits PKA activity independently of Hh signalling, and propose that Cxcr4a enhances Hh dependent proliferation by promoting the activity of Gli1. Our results indicate that Cxcr4a is required for Hh-dependent cell proliferation but not for Hh dependent patterning, and suggest that the parallel activation of Cxcr4a is required to modulate the Hh pathway to distinguish between patterning and proliferation. PMID- 22782723 TI - The Dorsocross T-box transcription factors promote tissue morphogenesis in the Drosophila wing imaginal disc. AB - The Drosophila wing imaginal disc is subdivided into notum, hinge and blade territories during the third larval instar by formation of several deep apical folds. The molecular mechanisms of these subdivisions and the subsequent initiation of morphogenic processes during metamorphosis are poorly understood. Here, we demonstrate that the Dorsocross (Doc) T-box genes promote the progression of epithelial folds that not only separate the hinge and blade regions of the wing disc but also contribute to metamorphic development by changing cell shapes and bending the wing disc. We found that Doc expression was restricted by two inhibitors, Vestigial and Homothorax, leading to two narrow Doc stripes where the folds separating hinge and blade are forming. Doc mutant clones prevented the lateral extension and deepening of these folds at the larval stage and delayed wing disc bending in the early pupal stage. Ectopic Doc expression was sufficient to generate deep apical folds by causing a basolateral redistribution of the apical microtubule web and a shortening of cells. Cells of both the endogenous blade/hinge folds and of folds elicited by ectopic Doc expression expressed Matrix metalloproteinase 2 (Mmp2). In these folds, integrins and extracellular matrix proteins were depleted. Overexpression of Doc along the blade/hinge folds caused precocious wing disc bending, which could be suppressed by co-expressing MMP2RNAi. PMID- 22782725 TI - EGFR-dependent network interactions that pattern Drosophila eggshell appendages. AB - Similar to other organisms, Drosophila uses its Epidermal Growth Factor Receptor (EGFR) multiple times throughout development. One crucial EGFR-dependent event is patterning of the follicular epithelium during oogenesis. In addition to providing inductive cues necessary for body axes specification, patterning of the follicle cells initiates the formation of two respiratory eggshell appendages. Each appendage is derived from a primordium comprising a patch of cells expressing broad (br) and an adjacent stripe of cells expressing rhomboid (rho). Several mechanisms of eggshell patterning have been proposed in the past, but none of them can explain the highly coordinated expression of br and rho. To address some of the outstanding issues in this system, we synthesized the existing information into a revised mathematical model of follicle cell patterning. Based on the computational model analysis, we propose that dorsal appendage primordia are established by sequential action of feed-forward loops and juxtacrine signals activated by the gradient of EGFR signaling. The model describes pattern formation in a large number of mutants and points to several unanswered questions related to the dynamic interaction of the EGFR and Notch pathways. PMID- 22782724 TI - fras1 shapes endodermal pouch 1 and stabilizes zebrafish pharyngeal skeletal development. AB - Lesions in the epithelially expressed human gene FRAS1 cause Fraser syndrome, a complex disease with variable symptoms, including facial deformities and conductive hearing loss. The developmental basis of facial defects in Fraser syndrome has not been elucidated. Here we show that zebrafish fras1 mutants exhibit defects in facial epithelia and facial skeleton. Specifically, fras1 mutants fail to generate a late-forming portion of pharyngeal pouch 1 (termed late-p1) and skeletal elements adjacent to late-p1 are disrupted. Transplantation studies indicate that fras1 acts in endoderm to ensure normal morphology of both skeleton and endoderm, consistent with well-established epithelial expression of fras1. Late-p1 formation is concurrent with facial skeletal morphogenesis, and some skeletal defects in fras1 mutants arise during late-p1 morphogenesis, indicating a temporal connection between late-p1 and skeletal morphogenesis. Furthermore, fras1 mutants often show prominent second arch skeletal fusions through space occupied by late-p1 in wild type. Whereas every fras1 mutant shows defects in late-p1 formation, skeletal defects are less penetrant and often vary in severity, even between the left and right sides of the same individual. We interpret the fluctuating asymmetry in fras1 mutant skeleton and the changes in fras1 mutant skeletal defects through time as indicators that skeletal formation is destabilized. We propose a model wherein fras1 prompts late-p1 formation and thereby stabilizes skeletal formation during zebrafish facial development. Similar mechanisms of stochastic developmental instability might also account for the high phenotypic variation observed in human FRAS1 patients. PMID- 22782726 TI - Electrocardiogram interpretation in the athlete. AB - The sudden death of a young athlete is a devastating event that impacts the lay public and medical community and has attracted efforts to screen for underlying cardiovascular diseases associated with sudden death in this population. Electrocardiography (ECG) screening has been shown to increase the sensitivity of finding structural heart diseases in competitive athletes. Recent research in diverse populations of athletes has led to refinements in ECG-interpretation standards designed to improve its diagnostic accuracy. This review summarizes relevant information regarding cardiovascular screening and ECG interpretation in athletes. PMID- 22782727 TI - The right heart in athletes. Evidence for exercise-induced arrhythmogenic right ventricular cardiomyopathy. AB - Although 'athlete's heart' usually constitutes a balanced dilation and hypertrophy of all four chambers, there is increasing evidence that intense endurance activity may particularly tax the right ventricle (RV), both acutely and chronically. We review the evidence that the high wall stress of the RV during intense sports may explain observed B-type natriuretic peptide (BNP) elevations immediately after a race, may lead to cellular disruption and leaking of cardiac enzymes, and may even result in transient RV dilatation and dysfunction. Over time, this could lead to chronic remodelling and a pro arrhythmic state resembling arrhythmogenic RV cardiomyopathy (ARVC) in some cases. ARVC in high-endurance athletes most often develops in the absence of underlying desmosomal abnormalities, probably only as a result of excessive RV wall stress during exercise. Therefore, we have labelled this syndrome 'exercise induced ARVC'. Sports cardiologists should be aware that excessive sports activity can lead to cardiac sports injuries in some individuals, just like orthopaedic specialists are familiar with musculoskeletal sports injuries. This does not negate the fact that moderate exercise has positive cardiovascular effects and should be encouraged. PMID- 22782728 TI - Sports participation in patients with implantable cardioverter-defibrillators. AB - The safety of sports participation for patients with implantable cardioverter defibrillators (ICDs) is not yet defined, and current recommendations in both Europe and the US restrict these patients from competative sports more vigorous than golf or bowling. Postulated risks include increased frequency of arrhythmias, inability of the ICD to terminate ventricular arrhythmias during the metabolic changes accompanying extreme exercise, injury to the patient, or damage to the ICD system. However, survey data suggest that many ICD patients do participate in sports, and risks may be fewer than postulated. Ongoing research will better delineate the risks of sports for patients with ICDs. PMID- 22782729 TI - Arrhythmias in the athlete. AB - Regular exercise provides substantial health benefits, mostly by reducing cardiovascular risk factors. However, it may also trigger acute cardiac events and cause sudden cardiac death in individuals with a pre-existing condition. In an otherwise healthy population, intense regular exercise may lead to morphological and electrical cardiac adaptations commonly referred as "athlete's heart." Recent data suggest that this may itself produce structural changes of atrial and ventricular myocardium with enlargement and fibrosis, creating the substrate for development of arrhythmias in apparently healthy athletes. The state of the art in this controversial issue is reviewed. PMID- 22782730 TI - The diagnosis and management of tinea. PMID- 22782732 TI - Prescribing proton pump inhibitors with clopidogrel. PMID- 22782733 TI - Does telemedicine deserve the green light? PMID- 22782731 TI - Clopidogrel and interaction with proton pump inhibitors: comparison between cohort and within person study designs. AB - OBJECTIVE: To measure the association between use of proton pump inhibitors and a range of harmful outcomes in patients using clopidogrel and aspirin. DESIGN: Observational cohort study and self controlled case series. SETTING: United Kingdom General Practice Research Database with linked data from the Myocardial Ischaemia National Audit Project (MINAP) and the Office for National Statistics (the cardiovascular disease research using linked bespoke studies and electronic records (CALIBER) collaboration) POPULATION: 24,471 patients receiving clopidogrel and aspirin. MAIN OUTCOME MEASURES: The primary outcome was death or incident myocardial infarction. Secondary outcomes were death, incident myocardial infarction, vascular death, and non-vascular death. Comparisons were made between proton pump inhibitor use and non-use. RESULTS: Of the 24,471 patients prescribed clopidogrel and aspirin, 12,439 (50%) were also prescribed a proton pump inhibitor at some time during the study. Death or incident myocardial infarction occurred in 1419 (11%) patients while they were receiving a proton pump inhibitor compared with 1341 (8%) who were not receiving a proton pump inhibitor. In multivariate analysis, the hazard ratio for the association between proton pump inhibitor use and death or incident myocardial infarction was 1.37 (95% confidence interval 1.27 to 1.48). Comparable results were seen for secondary outcomes and with other 2C19 inhibitors and with non-2C19 inhibitors. With the self controlled case series design to remove the effect of differences between people, there was no association between proton pump inhibitor use and myocardial infarction, with a rate ratio of 0.75 (0.55 to 1.01). Similarly, with the self controlled case series there was no association with myocardial infarction for other 2C19 inhibitors/non-inhibitors. CONCLUSION: The lack of a specific association and the discrepancy between findings of the analyses between and within people suggests that the interaction between proton pump inhibitors and clopidogrel is clinically unimportant. PMID- 22782734 TI - Only a fifth of L1.7bn NHS underspend will be carried into next year's budget. PMID- 22782735 TI - Activists call for more measured response to Tanzanian doctors' strike. PMID- 22782736 TI - Speed up access to contraceptives to save lives, say researchers. PMID- 22782737 TI - A randomized trial of a brief intervention to promote smoking cessation for parents during child hospitalization. AB - BACKGROUND: Parental smoking significantly increases the risk of child hospitalization for multiple illnesses. Parenting smokers may not have easy access to smoking cessation services elsewhere and a few interventions with this population in the inpatient setting have shown promising results. METHODS: We sought to evaluate the efficacy of a brief intervention with smoking parents on smoking cessation rates after child hospitalization with a randomized, controlled trial. RESULTS: Sixty smoking parents participated in the study. The majority of study participants were uninsured women under age 30 who smoked approximately half of a pack per day. There were no statistically significant differences between control and intervention groups for our outcomes. However, 45% (CI: 33 57%) of all participants reported at least one quit attempt during the 2-month study period and 18% (CI: 10-30%) of participants were quit at study conclusion. CONCLUSIONS: Willingness to quit smoking was much higher than expected in this population of parenting smokers. PMID- 22782738 TI - Work-related musculoskeletal disorders among Irish farm operators. AB - BACKGROUND: To establish prevalence, risk factors, and impact of work-related musculoskeletal disorders (WMSDs) among farmers in Ireland. METHODS: In summer 2009, a questionnaire was appended to the Teagasc (Irish Agricultural and Food Development Authority) National Farm Survey (n = 1,110) to obtain data on the prevalence, risk factors and impact of WMSDs amongst farm operators in Ireland. Data were collected by trained recorders and analyzed using chi-square tests, t tests, Mann-Whitney's U-tests and logistic regression models. RESULTS: The prevalence of WMSDs in the previous year was 9.4% (n = 103), with the most commonly affected body region being the low back 31% (n = 32). Nearly 60% (n = 57) of farmers reported missing at least a full day's work as a consequence of their WMSD. Personal factors evaluated using binary regression analysis, were found not to influence whether or not a farmer experienced a WMSD. However, work related factors such as larger European Size Units (ESUs, OR: 1.007, CI: 1.002 1.012), greater number of hectares farmed (OR: 2.501, CI: 1.208-4.920), higher income (OR: 1.859, CI: 1.088-3.177), dairy enterprise (OR: 1.734, CI: 1.081 2.781), and working on a full-time farm (OR: 2.156, CI: 1.399-3.321) increased the likelihood of experiencing a WMSD. Working on a full-time farm was the only factor found to independently predict WMSDs in the multiple regression analyses. CONCLUSIONS: This study suggests that the prevalence of WMSDs can be reduced by the application of improved farm management practices. A more detailed examination of the risk factors associated with WMSDs is required to establish causality and develop effective interventions. PMID- 22782739 TI - New tetraphosphorus ligands for highly linear selective hydroformylation of allyl and vinyl derivatives. AB - New tetraphosphorus ligands have been developed and applied in the rhodium catalyzed regioselective hydroformylation of a variety of functionalized allyl and vinyl derivatives. Remarkably high linear selectivity was obtained by these tetraphosphorus ligands. The ligand that bears strong electron-withdrawing 2,4 difluorophenyl groups is the most effective one in affording linear aldehydes. The Rh/tetraphosphorus ligand catalyst is highly effective to produce linear aldehydes from functionalized allyl derivatives with heteroatoms or aromatic groups directly adjacent to the allyl group. For vinyl derivatives, the ligand is highly linear selective for acrylic derivatives, styrene, vinyl pyridine, and vinyl phthalimide. Linear to branch ratios of 26:1 and 10:1 were obtained for the hydroformylation of styrene and allyl cyanide, respectively. PMID- 22782740 TI - A tribute to Henri H. Mollaret (1923-2008). PMID- 22782741 TI - Evolutionary dynamics of the Yersinia enterocolitica complex. PMID- 22782742 TI - Gains and Losses in Yersinia enterocolitica subsp. palearctica Genomes. PMID- 22782743 TI - Consequences of missense mutations in Yersinia pestis: efficient flow of metabolic carbon versus virulence. PMID- 22782744 TI - Diversity and adaptive evolution of a major porin gene (ompF) in Yersinia pseudotuberculosis. PMID- 22782745 TI - Biochemical and genetic peculiarities and the phylogenetic relationship of the non-main subspecies in the general scheme of the plague agent evolution. PMID- 22782746 TI - The molecular phylogeny of the gyrB gene: a molecular marker for systematic characterization of the genus Yersinia. PMID- 22782747 TI - Preliminary survey regarding yersiniosis in Ireland. PMID- 22782748 TI - Pseudotuberculosis in the Russian federation. PMID- 22782749 TI - Plague in Brazil: from now and then. PMID- 22782750 TI - Factors affecting the spread and maintenance of plague. PMID- 22782751 TI - Isolation of enteropathogenic Yersinia from non-human sources. PMID- 22782752 TI - Yersinia pseudotuberculosis O III causes diarrhea in Brazilian cattle. PMID- 22782753 TI - Prevalence, serotype, virulence characteristics, clonality, and antibiotic susceptibility of pathogenic Yersinia enterocolitica from Swine feces. PMID- 22782754 TI - Characterization of Yersinia enterocolitica 4/O:3 isolated from slaughterhouses and pork in the state of Sao Paulo, Brazil, and clinical cases in humans. PMID- 22782755 TI - Bacteriophages capable of lysing Yersinia pestis and Yersinia pseudotuberculosis: efficiency of plating tests and identification of receptors in escherichia coli K 12. PMID- 22782756 TI - Field and clinical applications of advanced bacteriophage-based detection of Yersinia pestis. PMID- 22782757 TI - Plague diagnosis STNPCR and MPCR kits assembly, reaction reproducibility, and reagent stability. PMID- 22782758 TI - Innate immune responses during infection with Yersinia pestis. PMID- 22782759 TI - The life stage of Yersinia pestis in the flea vector confers increased resistance to phagocytosis and killing by murine polymorphonuclear leukocytes. PMID- 22782760 TI - Phagocytes and humoral immunity to pneumonic plague. PMID- 22782761 TI - The in vitro evaluation of anti-plague cellular immunity by quantitative analysis of IFN-gamma synthesis and the appearance of activation molecules on the surface of T-helper cells. PMID- 22782762 TI - Cytotoxic necrotizing factor is an effective immunogen in a Yersinia pseudotuberculosis aerosol mouse model. PMID- 22782763 TI - Fimbrial polyadhesins: anti-immune armament of Yersinia. PMID- 22782764 TI - Yop effector proteins from Yersinia pseudotuberculosis impair dendritic cell activation. PMID- 22782765 TI - Impact on the host of the Yersinia pestis-specific virulence set and the contribution of the pla surface protease. PMID- 22782766 TI - Virulence of Yersinia pseudotuberculosis in aerosol models. PMID- 22782767 TI - Pathogenic potential of the Yersinia massiliensis species. PMID- 22782768 TI - Modulation of host cell death pathways by Yersinia species and the type III effector YopK. PMID- 22782769 TI - Biofilm-dependent and biofilm-independent mechanisms of transmission of Yersinia pestis by fleas. PMID- 22782770 TI - YopM and plague. PMID- 22782772 TI - Variability in the functional domains of the rho-modifying toxins of Yersinia pseudotuberculosis. PMID- 22782771 TI - Substrates of the plasminogen activator protease of Yersinia pestis. PMID- 22782773 TI - Yersinia pestis transition metal divalent cation transporters. PMID- 22782774 TI - Unique virulence properties of Yersinia enterocolitica O:3. PMID- 22782775 TI - Yersinia pestis autoagglutination is mediated by HCP-like protein and siderophore Yersiniachelin (Ych). PMID- 22782776 TI - Yersinia surface structures and bacteriophages. PMID- 22782778 TI - Regulation of virulence gene expression by regulatory RNA elements in Yersinia pseudotuberculosis. PMID- 22782777 TI - Global discovery of small noncoding RNAs in pathogenic Yersinia species. PMID- 22782779 TI - OmpR, a central integrator of several cellular responses in Yersinia enterocolitica. PMID- 22782780 TI - Bacteriophage therapy of experimental bubonic plague in mice. PMID- 22782781 TI - Preliminary pharmacokinetics of the bacterial virulence inhibitor n'-(3,5-dibromo 2-hydroxy-benzylidenene)-nicotinic Acid hydrazide. PMID- 22782782 TI - Small molecule screening for inhibitors of the YopH phosphatase of Yersinia pseudotuberculosis. PMID- 22782783 TI - Combined hepatocellular carcinoma-cholangiocarcinoma: report of MR appearance in eleven patients. AB - PURPOSE: To describe the magnetic resonance imaging (MRI) appearance of hepatic combined hepatocellular-cholangiocarcinoma (cHCC-CC) in 11 patients. MATERIALS AND METHODS: The database of the Department of Pathology was cross-referenced with the MRI database to identify patients with confirmed cHCC-CC who had undergone MRI. Eleven consecutive patients were included (seven female, mean age 57.6 years). All patients were Caucasian. Five of 11 had a clinical history of chronic liver disease. Two radiologists retrospectively analyzed the images in consensus. RESULTS: cHCC-CC was a single mass in 10/11 patients. Margins were well-defined in 6/11. All tumors showed heterogeneous hyperintensity on T2. On postcontrast imaging, 6/11 showed early ring-enhancement (four noncirrhotic), with progressive enhancement in central portions, and 5/11 patients showed a diffuse heterogeneous early enhancement. Three of these five were cirrhotic and displayed partial washout with portions of contrast retention on later phases. Other findings included: late capsule enhancement (two patients), biliary dilatation (one), venous invasion (three), lymphadenopathy (six), and findings of cirrhosis (five). CONCLUSION: cHCC-CC presents most commonly as a single mass. Five of 11 had MR findings of cirrhosis. Clues to the diagnosis were moderately high signal on T2, portions of tumor that show progressive enhancement/contrast retention, and frequent lack of capsule. Early enhancement patterns included early ring-enhancement and diffuse heterogeneous enhancement. PMID- 22782784 TI - Controlling state of breathing of two isoreticular microporous metal-organic frameworks with triazole homologues. AB - Breathing effect: Using two triazole homologues (1H-benzotriazole and 1,2,3-1H triazole), two isoreticular microporous Zn-benzenedicarboxylate frameworks 1 and 2 with reverse dynamic features are presented, in which different sized triazole ligands effectively control the state of breathing of two flexible frameworks. PMID- 22782785 TI - RMC_POT: a computer code for reverse Monte Carlo modeling the structure of disordered systems containing molecules of arbitrary complexity. AB - An approach has been devised and tested for preserving the molecular dynamics molecular geometry taking into account energetic considerations during Reverse Monte Carlo (RMC) modeling. Instead of the commonly used fixed neighbor constraints, where molecules are held together by constraining distance ranges available for the specified atom pairs, here molecules are kept together via bond, angle, and dihedral potential energies. The scaled total potential energy contributes to the measure of the goodness-of-fit, thus, the atoms can be prevented from drifting apart. In some of the calculations (Lennard-Jones and Coulombic) nonbonding potentials were also applied. The algorithm was successfully tested for the X-ray structure factor-based structure study of liquid dimethyl trisulfide, for which material now significantly more sensible results have been obtained than during previous attempts via any earlier version of RMC modeling. It is envisaged that structural modeling of a large class of materials, primarily liquids and amorphous solids containing molecules of up to about 100 atoms, will make use of the new code in the near future. PMID- 22782786 TI - Left atrial appendage aneurysm: an unusual cause of hematuria with stroke. PMID- 22782787 TI - After the FEAST--fluid resuscitation in pediatric sepsis. PMID- 22782788 TI - Terretonin biosynthesis requires methylation as essential step for cyclization. PMID- 22782789 TI - Sexual behavior as a function of stigma and coping with stigma among people with HIV/AIDS in rural New England. AB - The relationship between coping with HIV/AIDS stigma and engaging in risky sexual behavior (i.e., inconsistent condom use) was examined in HIV-positive adults living in rural areas. Participants answered questions about their experiences with HIV/AIDS prejudice and discrimination (enacted stigma) and their perceptions of felt HIV/AIDS stigma (disclosure concerns, negative self-image, and concern with public attitudes). They were also asked about how they coped with HIV/AIDS stigma, and about their sexual activity during the past 90 days. We hypothesized that using disengagement coping to manage the stress of HIV/AIDS stigma would be related to risky sexual behavior. Multinomial logistic regression results showed that using disengagement coping (avoidance, denial, and wishful thinking) coupled with high levels of enacted stigma was associated with less risky rather than more risky sexual behavior. That is, disengagement coping coupled with high stigma increased the odds of not having vaginal or anal sex versus inconsistently using condoms. Implications for people with HIV/AIDS who use disengagement coping to manage stress to deal with HIV/AIDS stigma are discussed. PMID- 22782790 TI - Motherhood and HIV risk among female sex workers in Andhra Pradesh, India: the need to consider women's life contexts. AB - This study examines whether the challenges of motherhood among female sex workers (FSW) are linked with vulnerability to sexual risk factors for HIV. FSW at least 18 years of age (n = 850) were recruited through respondent driven sampling for a survey on HIV risk in the Rajahmundry area of Andhra Pradesh, India. Logistic regression models adjusted for demographic characteristics were used to assess the relation between reported caretaking challenges and sexual risk indicators for HIV. In adjusted logistic regression models, FSW who reported three or more children in their household or current child health concerns were significantly less likely to report consistent condom use (adjusted odds ratios (AORs) range: 0.5-0.6) and more likely to take more money for sex without a condom (both AORs: 2.5). Women who reported current child health concerns were also more likely to report an STI symptom in the past 6 months (AOR = 1.6; 95 % confidence interval: 1.1-2.3). Findings suggest that challenging responsibilities related to caretaking of children are associated with heightened vulnerability to HIV risk among FSW. Such findings add to the cumulating evidence urging for the implementation of HIV prevention interventions that consider the multiple challenges across various domains of women's lives. PMID- 22782791 TI - Preference between precoital and daily use of Duet(r) and BufferGel in Zimbabwe. AB - Duet(r) is a microbicide-delivery system and cervical barrier for use daily or precoitally. We conducted a crossover study among 80 Zimbabwean women to explore factors associated with use-regimen preference. Women were assigned in random order to 14 days of precoital and 14 days of daily Duet and BufferGel use. About 51 % of women preferred precoital use, 39 % preferred daily use, and 10 % liked both equally. Overall product adherence during sex was similar for both use regimens. In multivariable analysis, diaphragm experience was associated with preference for precoital use (AOR 2.80, 95 % CI 1.01-7.76). Reasons for preferring precoital use included use only when needed, cleanliness, and discomfort with daily use. Daily use preference included convenience, discreetness, and being prepared for "sex-on-demand." Different personal and life circumstances may result in varying use-regimen preferences. Methods that can accommodate both coitally-related and daily use may be advantageous by providing more choice to users. PMID- 22782792 TI - Silver behaviour along the salinity gradient of the Gironde Estuary. AB - Dissolved and particulate Ag concentrations (Ag(D) and Ag(P), respectively) were measured in surface water and suspended particulate matter (SPM) along the salinity gradient of the Gironde Estuary, South West France, during three cruises (2008-2009) covering contrasting hydrological conditions, i.e. two cruises during intermediate and one during high freshwater discharge (~740 and ~2,300 m(3)/s). Silver distribution reflected non-conservative behaviour with 60-70 % of Ag(P) in freshwater particles being desorbed by chlorocomplexation. The amount of Ag(P) desorbed was similar to the so-called reactive, potentially bioavailable Ag(P) fraction (60 +/- 4 %) extracted from river SPM by 1 M HCl. Both Ag(P) (0.22 +/- 0.05 mg/kg) and Ag(P)/Th(P) (0.025-0.028) in the residual fraction of fluvial and estuarine SPM were similar to those in SPM from the estuary mouth and in coastal sediments from the shelf off the Gironde Estuary, indicating that chlorocomplexation desorbs the reactive Ag(P). The data show that desorption of reactive Ag(P) mainly occurs inside the estuary during low and intermediate discharge, whereas expulsion of partially Ag(P)-depleted SPM (Ag(P)/Th(P) ~0.040) during the flood implies ongoing desorption in the coastal ocean, e.g. in the nearby oyster production areas (Marennes-Oleron Bay). The highest Ag(D) levels (6 8 ng/L) occurred in the mid-salinity range (15-20) of the Gironde Estuary and were decoupled from freshwater discharge. In the maximum turbidity zone, Ag(D) were at minimum, showing that high SPM concentrations (a) induce Ag(D) adsorption in estuarine freshwater and (b) counterbalance Ag(P) desorption in the low salinity range (1-3). Accordingly, Ag behaviour in turbid estuaries appears to be controlled by the balance between salinity and SPM levels. The first estimates of daily Ag(D) net fluxes for the Gironde Estuary (Boyle's method) showed relatively stable theoretical Ag(D) at zero salinity (Ag (D) (0) = 25-30 ng/L) for the contrasting hydrological situations. Accordingly, Ag(D) net fluxes were very similar for the situations with intermediate discharge (1.7 and 1.6 g/day) and clearly higher during the flood (5.0 g/day) despite incomplete desorption. Applying Ag (D) (0) to the annual freshwater inputs provided an annual net Ag(D) flux (0.64-0.89 t/year in 2008 and 0.56-0.77 t/year in 2009) that was 12-50 times greater than the Ag(D) gross flux. This estimate was consistent with net Ag(D) flux estimates obtained from gross Ag(P) flux considering 60 % desorption in the estuarine salinity gradient. PMID- 22782793 TI - Effect of diflubenzuron on the development of Pinus pinaster seedlings inoculated with the ectomycorrhizal fungus Pisolithus tinctorius. AB - Diflubenzuron (DFB) is an insecticide commonly used to control forest pests. The objectives of this study were to assess the effect of diflubenzuron on the development of Pinus pinaster seedlings and Pisolithus tinctorius under laboratory conditions and to study the possible protective role of this ectomycorrhizal fungus against the effects of diflubenzuron. In vitro experiments revealed that diflubenzuron inhibited fungal growth at all tested concentrations (0.01, 0.1, 1, 10 and 100 mg L(-1)). Root growth was inhibited at the two highest diflubenzuron concentrations. The activity of the antioxidant defence system of non-inoculated P. pinaster increased at 1 and 10 mg DFB kg(-1) substrate, and inoculation increased the threshold to the highest concentration. The protective role of the ectomycorrhizal fungus was seen in the increase of CAT activity. This study revealed that despite causing no mortality, diflubenzuron has the ability to cause sub-lethal damage to P. pinaster. The disproportionate use of this insecticide may lead to higher amounts of its residues in soil and the biosphere, endangering trees, fungi and their symbiosis. PMID- 22782801 TI - Inhibition enhances memory capacity: optimal feedback, transient replay and oscillations. AB - Recurring sequences of neuronal activation in the hippocampus are a candidate for a neurophysiological correlate of episodic memory. Here, we discuss a mean-field theory for such spike sequences in phase space and show how they become unstable when the neuronal network operates at maximum memory capacity. We find that inhibitory feedback rescues replay of the sequences, giving rise to oscillations and thereby enhancing the network's capacity. We further argue that transient sequences in an overloaded network with feedback inhibition may provide a mechanistic picture of memory-related neuronal activity during hippocampal sharp wave ripple complexes. PMID- 22782794 TI - Design of graphene-based TiO2 photocatalysts--a review. AB - There is a recent increase in the interest of designing high-performance photocatalysts using graphene-based materials. This review gathers some important aspects of graphene-TiO(2), graphene oxide-TiO(2), and reduced graphene oxide TiO(2) composites, which are of especial relevance as next generation photocatalysts. The methods used for the preparation of these materials, the associated mechanistic fundamentals, and the application of graphene-based composites on the photocatalytic degradation of pollutants are reviewed. Some structural, textural, and chemical properties of these materials and other photo assisted applications, such as hydrogen production from water splitting and dye sensitized solar cells, are also briefly included. PMID- 22782802 TI - Human UDP-glucuronosyltransferase expression in insect cells: ratio of active to inactive recombinant proteins and the effects of a C-terminal his-tag on glucuronidation kinetics. AB - Many laboratories use recombinant UDP-glucuronosyltransferases (UGTs), expressed in baculovirus-infected insect cells, for drug glucuronidation studies. We have infected Sf9 insect cells with increasing amounts of recombinant baculovirus, encoding either UGT1A9 or UGT2B7, and measured both glucuronidation activity and immunodetectable UGT in the resulting cell homogenates. The correlation between glucuronidation rates and degree of infection followed different trends, depending on whether activity was the actual activity measured or was corrected for UGT expression level. Above a certain low level of infection, further increases in infection ratios led to a large decline in normalized activity, presumably due to the presence of full-length but inactive enzyme in the sample. Because immunodetection does not distinguish between active and inactive UGT, comparison of normalized activity between different batches of a recombinant UGT, mutants of a given UGT, or different UGTs is prone to large inaccuracies. Such inaccuracies could be reduced by lowering the degree of infection of the insect cells, in combination with careful monitoring of UGT expression. However, the latter requires suitable antibodies for comparing UGT expression levels among preparations, antibodies that are not always available. Poly-His (His-tag) containing peptides, fused to the UGT C terminus, allow sensitive immunodetection of expressed enzymes with monoclonal antibodies. We have now carefully examined the effects of two such fusion peptides on enzyme kinetics. A minor increase in the K(m) values has been detected in the His-tagged UGTs, but no changes in parameters such as the kinetic model and the effects of albumin addition. PMID- 22782804 TI - Is biodegradable waste a porous environment? A review. AB - This article presents a review of the porous physical characteristics, phenomena and simulation models so far investigated and applied in the management of biodegradable wastes (BW), summarising the main properties of porous media and the dynamics of fluids within its voids. The aim is to highlight how the description of biodegradable wastes as porous media and the use of porous media models can facilitate the development of new sustainable and affordable technologies for BW recycling. However, it is pointed out how the lack of physical experimental data and of tailored modelling tools has so far hampered the use of this approach. Therefore, it is suggested that a simpler way to design and implement modelling tools simulating BW treatment technologies is by modifying available models designed originally for other porous media, such as soil and rock. PMID- 22782803 TI - Impact of physician preferences for homeopathic or conventional medicines on patients with musculoskeletal disorders: results from the EPI3-MSD cohort. AB - OBJECTIVE: The objective of this study was to assess the effect of physician practicing preferences (PPP) in primary care for homeopathy (Ho), CAM (Complementary and alternative medicines) with conventional medicine (Mx) or exclusively conventional medicine (CM) on patients with musculoskeletal disorders (MSDs), with reference to clinical progression, drug consumption, side effects and loss of therapeutic opportunity. METHODS: The EPI3-MSD study was a nationwide observational cohort of a representative sample of general practitioners (GP) and their patients in France. Recruitment of GP was stratified by PPP, which was self declared. Diagnoses and comorbidities were recorded by GP at inclusion. Patients completed a standardized telephone interview at inclusion, one, three and twelve months, including MSD-functional scales and medication consumption. RESULTS: 1153 MSD patients were included in the three PPP groups. Patients did not differ between groups except for chronicity of MSDs (>12 weeks), which was higher in the Ho group (62.1%) than in the CM (48.6%) and Mx groups (50.3%). The twelve-month development of specific functional scores was identical across the three groups after controlling for baseline score (p > 0.05). After adjusting for propensity scores, NSAID use over 12 months was almost half in the Ho group (OR, 0.54; 95%CI, 0.38-0.78) as compared to the CM group; no difference was found in the Mx group (OR, 0.81; 95% CI: 0.59-1.15). CONCLUSION: MSD patients seen by homeopathic physicians showed a similar clinical progression when less exposed to NSAID in comparison to patients seen in CM practice, with fewer NSAID-related adverse events and no loss of therapeutic opportunity. PMID- 22782805 TI - Supramolecular binding thermodynamics by dispersion-corrected density functional theory. AB - The equilibrium association free enthalpies DeltaG(a) for typical supramolecular complexes in solution are calculated by ab initio quantum chemical methods. Ten neutral and three positively charged complexes with experimental DeltaG(a) values in the range 0 to -21 kcal mol(-1) (on average -6 kcal mol(-1)) are investigated. The theoretical approach employs a (nondynamic) single-structure model, but computes the various energy terms accurately without any special empirical adjustments. Dispersion corrected density functional theory (DFT-D3) with extended basis sets (triple-zeta and quadruple-zeta quality) is used to determine structures and gas-phase interaction energies (DeltaE), the COSMO-RS continuum solvation model (based on DFT data) provides solvation free enthalpies and the remaining ro-vibrational enthalpic/entropic contributions are obtained from harmonic frequency calculations. Low-lying vibrational modes are treated by a free-rotor approximation. The accurate account of London dispersion interactions is mandatory with contributions in the range -5 to -60 kcal mol(-1) (up to 200% of DeltaE). Inclusion of three-body dispersion effects improves the results considerably. A semilocal (TPSS) and a hybrid density functional (PW6B95) have been tested. Although the DeltaG(a) values result as a sum of individually large terms with opposite sign (DeltaE vs. solvation and entropy change), the approach provides unprecedented accuracy for DeltaG(a) values with errors of only 2 kcal mol(-1) on average. Relative affinities for different guests inside the same host are always obtained correctly. The procedure is suggested as a predictive tool in supramolecular chemistry and can be applied routinely to semirigid systems with 300-400 atoms. The various contributions to binding and enthalpy-entropy compensations are discussed. PMID- 22782806 TI - Systemic studies of tetraphenylethene-triphenylamine oligomers and a polymer: achieving both efficient solid-state emissions and hole-transporting capability. AB - By employing a new synthetic strategy, a series of oligomers and a polymer composed of different number of tetraphenylethene and triphenylamine units was designed and synthesised. The optical physics properties and electroluminescence behaviours were studied comparatively. All the molecules demonstrate an aggregation-induced emission (AIE) phenomenon and bear very high quantum yields in the solid state. The emission wavelengths and quantum efficiencies alternate with the change of the molecular configurations and achieve their maximum at the largest oligomer. The thermal stabilities also become higher along with the increase in the molecular weight. The molecules have suitable HOMO levels that match the work function of the indium tin oxide (ITO) anode. They can act as both light-emitting and hole-transporting materials in OLEDs. Thus the present strategy combines the intrinsic emissive nature of AIE materials and the good hole-transport capability of aromatic amines, thereby achieving a win-win for both optical and electrical properties. PMID- 22782807 TI - Exhaled eicosanoid profiles in children with atopic asthma and healthy controls. AB - RATIONALE: Chronic endobronchial inflammation is a hallmark of pediatric asthma and involves the arachidonic acid pathway. Its non-volatile metabolites can be quantified in the exhaled breath condensate (EBC), and single substances have been studied as non-invasive biomarkers for the diagnosis and monitoring of children with asthma. The aim of this study was to compare the content and profile of a wider range of eicosanoids in the EBC between patients and a control group. MATERIALS AND METHODS: EBC was sampled from 33 children (aged 12.4 +/- 3.1 years) with stable atopic asthma (26 on inhaled steroid treatment) and 25 healthy controls (11.8 +/- 3.2 years). Validated high performance liquid chromatography coupled with a tandem mass spectrometry platform (HPLC-MS2 ) was used to measure 13 different compounds. In addition, exhaled nitric oxide levels (FeNO) were measured and bronchial hyperresponsiveness (BHR) was assessed by an exercise challenge test in all subjects. An analytical approach was used for multivariate regression modeling of disease status using the most relevant variables. RESULTS: The levels of PGEM (P < 0.001), PGD2 (P < 0.001), 6keto-PGF1alpha (P = 0.03), LTC4 (P < 0.001), trans-LTC4 (P = 0.04), and 5HETE (P = 0.02) were significantly higher in asthmatics compared to healthy children, while 11-dehydro TXB2 was significantly less abundant (P = 0.02). The eicosanoids asthma classification ratio (EACR) was computed as the logistic regression function using four variables: PGEM, PGD2, LTC4, and 5HETE. This composite parameter discriminated asthmatic from healthy children better than FEV1, FeNO, or BHR. CONCLUSION: Complementary measurements of PGEM, PGD2, LTC4, and 5HETE in small-volume EBC samples are feasible by HPLC-MS2 and showed a specific profile in our study population. EACR should be evaluated further in the context of diagnosing and monitoring childhood asthma. PMID- 22782808 TI - Overview of molecular biological methods for the detection of pathogens causing sexually transmitted infections. AB - We review here different state-of-the-art molecular methods currently used in the diagnosis of sexually transmitted infections. PMID- 22782809 TI - Guidelines for the qualitative detection of viral genomes in dried blood spots. AB - Dried blood spots (DBSs) are a useful alternative to blood sampling especially in children or for screening high-risk populations in developing countries. DBS blood collection can be employed in the diagnosis of viral infections by PCR or RT-PCR and also in viral genome sequencing. In addition, the advent of multiplex PCR approaches has led to further diagnostic and methodological improvements allowing simultaneous detection of two or more different viral genomes in the same sample and amplification reaction. This chapter describes general guidelines for the qualitative viral genome amplification and detection in DBS providing an example application of a qualitative real-time SYBR Green-based multiplex RT-PCR assay targeting two major viral pathogens, HIV-1 and HCV. PMID- 22782810 TI - Guidelines for the quantification of HIV and HCV in small volume whole blood samples. AB - The quantification of Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) in whole blood provides several advantages over the quantification in plasma samples. The application of small samples of capillary blood allows for application in point-of-care diagnostic testing methods.Here we describe two protocols of extracting viral RNA from small samples of whole blood by hybridization to biotinylated LNA-modified 2'-O-Methyl-RNA or to biotinylated DNA, indirect capturing to streptavidin-coated beads, and subsequent quantification by one-step non-nested qRT-PCR. Further, we provide some general guidelines on extraction and quantification of HIV and HCV in small volume whole blood samples. PMID- 22782811 TI - Guidelines for high-resolution genotyping of Chlamydia trachomatis using multilocus sequence analysis. AB - Chlamydia is one of the most common sexually transmitted infections worldwide and can cause ectopic pregnancies and infertility. It is therefore important to have adequate genotyping tools for investigating the spread of Chlamydia trachomatis among the population. Here, we describe a high-resolution multilocus sequence typing (MLST) system able to differentiate closely related clinical strains, which makes it ideal for short-term epidemiology and outbreak investigations. It is based on five highly variable but stable target regions which are PCR amplified and DNA sequenced. PMID- 22782812 TI - Guidelines for the use of molecular tests for the detection and genotyping of human papilloma virus from clinical specimens. AB - Accurate genotyping of a human papilloma virus (HPV) isolated from clinical specimens depends on molecular identification of the unique and exclusive nucleotide base sequence in the hypervariable region of a highly conserved segment of the HPV L1 gene. Among other options, a heminested (nested) polymerase chain reaction (PCR) technology using two consecutive PCR replications of the target DNA in tandem with three consensus general primers may be used to detect a minute quantity of HPV DNA in crude proteinase K digestate of cervicovaginal cells, and to prepare the template for genotyping by automated direct DNA sequencing. A short target sequence of 40-60 bases excised from the computer generated electropherogram is sufficient for BLAST determination of all clinically relevant HPV genotypes, based on the database stored in the GenBank. This chapter discusses the principle and the essential technical elements in performing nested PCR DNA amplification for the detection of HPV from clinical specimens and short target sequence genotyping for HPV, using standard molecular biology laboratory equipment and commercially available reagents. PMID- 22782813 TI - The molecular diagnosis of sexually transmitted genital ulcer disease. AB - Highly sensitive and specific nucleic acid amplification tests (NAATs) have emerged as the gold standard diagnostic tests for many infectious diseases. Real time PCR has further refined the technology of nucleic acid amplification with detection in a closed system and enabled multiplexing to simultaneously detect multiple pathogens. It is a versatile, fast, and high-throughput system for pathogen detection that has reduced the risk of PCR contamination, eliminated post-PCR manipulations, and improved the cost-effectiveness of testing. In addition, real-time PCR can be applied to self-collected noninvasive specimens. Here, we describe an in-house developed TaqMan-based real-time multiplex PCR (M PCR) assay for the diagnosis of sexually transmitted genital ulcer disease (GUD) and discuss briefly on issues associated with validation of assay performance. PMID- 22782814 TI - Validation of a sensitive and specific real-time PCR for detection and quantitation of hepatitis B virus covalently closed circular DNA in plasma of chronic hepatitis B patients. AB - Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) serves as a template for viral replication and plays a role in persistence of HBV infection. The origin and significance of cccDNA in plasma, however, are not well understood. A sensitive, specific, and reproducible real-time PCR for detection and quantitation of cccDNA in plasma of chronic hepatitis B patients was developed and validated. Four HBV DNA reference panels and 96 plasma samples of chronic hepatitis B patients are analyzed. Results are compared with total HBV DNA levels. This cccDNA assay had a lower limit of detection at 15 copies/PCR, a lower limit of quantitation at 91 copies/PCR, and a correlation coefficient (R) of 0.98 (p < 0.0001). HBV cccDNA can be detected in two of four international panels. Significant correlation is found between cccDNA and total HBV DNA levels in both panels (R = 0.96 and R = 0.43) and in samples of the chronic hepatitis B patients (R = 0.88, p < 0.0001). In 57 % of these samples cccDNA can be detected. Mean level of cccDNA is 0.16 % of total HBV load. Plasma HBV cccDNA levels are higher in HBeAg-positive samples than in HBeAg-negative samples (p < 0.0001). Total HBV DNA levels and HBV genotype do not influence cccDNA detection. PMID- 22782815 TI - Protocol for the detection of Mycoplasma genitalium by PCR from clinical specimens and subsequent detection of macrolide resistance-mediating mutations in region V of the 23S rRNA gene. AB - Mycoplasma genitalium is an established cause of male nongonococcal urethritis, in particular in cases with recurrent disease and in those negative for Chlamydia trachomatis. In women M. genitalium causes cervicitis and there is increasing evidence that it is causing pelvic inflammatory disease (PID). Nucleic acid amplification tests are currently the only available methods for detection, but no commercially available tests have been thoroughly evaluated. Here we describe a TaqMan-based PCR test for detection of the infection and a conventional PCR that serves as a confirmatory assay with the possibility of sequencing the product for detection of macrolide resistance-mediating mutations. PMID- 22782816 TI - Protocols for detection and typing of Treponema pallidum using PCR methods. AB - Syphilis, caused by Treponema pallidum, is a sexually transmitted disease which was epidemic in Europe between the 15th and 20th century. From 2000 onwards it is worldwide mostly encountered among men who have sex with men but also among women in resource poor setting. Syphilis can easily be treated with penicillin but can become chronic, if left untreated. The disease develops in several stages with ulcerative lesions in the primary stage, and systemic spread to organs via the blood in later stages. Taking swab samples from these ulcerative lesions gives the best options for detection by PCR of T. palillidum. Alternatively blood samples can be analyzed in later stages. If tested positive in screening PCR assays, T. pallidum can also be typed by molecular methods, enabling molecular epidemiology. Different protocols are discussed in this chapter, that include all steps from sample collection, nucleic acid extraction, PCR, and detection. The combination of all steps together determine the final sensitivity and specificity of T. pallidum PCR. PMID- 22782817 TI - Extraction of DNA from dried blood in the diagnosis of congenital CMV infection. AB - Viral DNA detection in dried blood spotted on filter paper, dried blood spots (DBS), is valuable in the diagnosis of viral infections, with at the moment congenital cytomegalovirus (CMV) being the most common application. CMV detection in clinical samples taken within the first 2-3 weeks after birth differentiates congenital CMV infection from the in general harmless postnatal acquired cytomegalovirus infection. DBS render the possibility to diagnose congenital CMV infection retrospectively, e.g., when late-onset hearing loss, the most frequently encountered symptom of congenital CMV infection, becomes manifest. Additionally, CMV DNA detection in DBS can be of usage in recently advocated newborn screening on congenital CMV infection. The procedure of CMV DNA detection in DBS consists of two separate steps: (1) DNA extraction from the DBS, followed by (2) CMV DNA amplification. Here, we describe two efficient methods for the extraction of DNA from DBS. Sensitivity, specificity, and applicability of the methods for high-throughput usage are discussed. PMID- 22782818 TI - Protocol for the use of PCR-denaturing gradient gel electrophoresis and quantitative PCR to determine vaginal microflora constitution and pathogens in bacterial vaginosis. AB - In healthy women, the vaginal ecosystem is dominated by Lactobacillus spp., but a diverse array of other bacteria can be present in lower amounts. The activity of lactobacilli is essential to protect women from genital infections and to maintain the natural healthy balance of the vaginal microbiota. Bacterial vaginosis (BV) is a complex, polymicrobial disorder characterized by an overgrowth of strict or facultative anaerobic bacteria and a reduction of lactobacilli. Culture-independent techniques based on the analysis of rRNA gene sequences provide powerful tools to reveal the phylogenetic diversity of the vaginal microorganisms in healthy women and patients affected by BV. Polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis conducted with universal primers for eubacteria allows detecting the most abundant bacterial species of an ecosystem. Sequencing of the DNA fragments and comparison with sequences present in publicly available databases allow identifying the corresponding bacterial species. Quantitative PCR is a powerful technique for the quantitative analysis of a selected genus or species. PMID- 22782819 TI - Protocol for the use of a bead array for the multiple detection of genotype of Chlamydia trachomatis. AB - The identification of Chlamydia trachomatis genotypes is important for both molecular epidemiology and infection control such as contact tracing and identification of high-risk groups. Currently, at least 19 human serovars have been recognized by using polyclonal and monoclonal antibodies against the major outer membrane protein. In sexually transmitted diseases, multiple pathogens or genotype infections are not uncommon. Hence, detection of multiple gene targets in one reaction is becoming increasingly important. Here, we describe the multiplex detection of eight genotypes of C. trachomatis by a combination of a PCR amplification with a multiplex bead array detection. The bead array system comprises distinct bead sets, which are color coded by different fluorescent intensities and a dual-laser flow cytometer analyzer to identify the identity of the bead and the intensity of the reporter dye that binds to the target molecules. The DNA sequences of the variable segments (VS2 or VS1-VS2) in outer membrane protein (omp1) gene are PCR amplified and biotin labeled and used as a gene target for the genotyping of C. trachomatis. Genotype-specific probes coupled to beads are used for capturing the labeled target amplicons through specific hybridization. Thus, multiple genotypes are detected and differentiated simultaneously by yielding quantitative data. PMID- 22782820 TI - Protocol for the detection and genotyping of human papillomaviruses using a liquid bead microarray assay. AB - More than 100 human papillomavirus (HPV) types have been identified, and over 40 of them infect the anogenital epithelium. Because each HPV type is associated with different risks for the development of cervical cancer, detecting and genotyping HPVs has increasingly become an integral part of cervical cancer control. Here, we describe a Luminex assay-based liquid bead microarray assay for genotyping 37 HPV types, which is objective, scalable, amenable to a high throughput configuration, and has the potential to be automated. PMID- 22782821 TI - Protocol for the use of enzyme-linked hybridization assays for genital ulcer disease. AB - Etiologic agents of genital ulcer disease include herpes simplex 1 and 2, Treponema pallidum pallidum, Haemophilus ducreyi, and Klebsiella granulomatis. The advent of PCR has allowed for more rapid and sensitive detection of microbial pathogens. In this protocol, we describe the simultaneous detection of these five pathogens and an internal control using a single-tube multiplex PCR and colorimetric enzyme-linked amplicon hybridization assay. PMID- 22782822 TI - Protocol for the rapid detection of the urogenital tract mollicutes and Chlamydia with concomitant LGV-(sub)typing. AB - Urogenital tract infections can be caused by a number of pathogens, some of which, like the obligate intracellular Chlamydia trachomatis, are difficult to culture, or the cell wall-less mollicutes, like M. hominis or Ureaplasma spp. Real-time PCR (qPCR) has become an important diagnostic tool as it enables not only the species-specific detection of the organism but also the quantification essential to define the etiological relevance of a facultative pathogenic bacterium. We developed a set of TaqMan qPCRs for the detection of the species M. genitalium and M. hominis (Mh/Mg-duplex qPCR), U. parvum and U. urealyticum (Uu/Up duplex-PCR), and C. trachomatis (CT-qPCR), and for typing of lymphogranuloma venereum-associated L-serovars of C. trachomatis (LGV-qPCR) as well as a sub-typing of L1, L2, and L3. In addition, the human gap-gene was amplified as quality control of the specimen, and a cryptic plasmid co-amplified in CT-qPCR as an inhibition control. The present protocol focuses on the step-by step description for the establishment of these TaqMan multiplex qPCRs. PMID- 22782823 TI - Protocol for the use of self-reporting duplex mutation primers to detect PCR products in the diagnosis of HBV. AB - Quantitative measurements of serum hepatitis B virus (HBV) DNA are useful for tailoring of treatment schedules and the monitoring of HBV replication during therapy. We developed a novel fluorescence-based quantitative real-time PCR for quantitating HBV DNA based on the duplex mutation primers principle, in which signal is generated by melting a duplex mutation primer during renaturation. The duplex mutation primers are much more specific than double-stranded DNA dyes like SYBR Green I and, unlike other probes, do not require the double-labeled synthesis of fluorophore and quencher on the same molecule. PMID- 22782824 TI - Protocol for the use of a rapid real-time PCR method for the detection of HIV-1 proviral DNA using double-stranded primer. AB - This chapter describes a real-time PCR method for the detection of HIV-1 proviral DNA in whole blood samples using a novel double-stranded primer system. The assay utilizes a simple commercially available DNA extraction method and a rapid and easy-to-perform real-time PCR protocol to consistently detect a minimum of four copies of HIV-1 group M proviral DNA in as little as 90 min after sample (whole blood) collection. Co-amplification of the human RNase P gene serves as an internal control to monitor the efficiency of both the DNA extraction and amplification. Once the assay is validated properly, it may be suitable as an alternative confirmation test for HIV-1 infections in a variety of HIV testing venues including the mother-to-child transmission testing sites, clinics, and diagnostic testing centers. PMID- 22782825 TI - Protocol for the use of light upon extension real-time PCR for the determination of viral load in HBV infection. AB - Real-time PCR has engendered wide acceptance for quantitation of hepatitis B virus (HBV) DNA in the blood due to its improved rapidity, sensitivity, reproducibility, and reduced contamination. Here we describe a cost-effective and highly sensitive HBV real-time quantitative assay based on the light upon extension real-time PCR platform and a simple and reliable HBV DNA preparation method using silica-coated magnetic beads. PMID- 22782826 TI - Protocol for the use of a silica nanoparticle-enhanced microcantilever sensor based method to detect HBV at femtomolar concentrations. AB - DNA sensors that are capable of detecting specific DNA sequences in a bio-sample have recently been highlighted as a powerful and sensitive approach to detect infectious diseases caused by pathogens such as viruses and bacteria. Generally, DNA samples extracted from biological fluids are amplified by PCR prior to analysis by DNA sensors or directly analyzed by DNA sensors equipped with a signal amplification process. Nanoparticles have recently been used to amplify the sensor signal and have been shown to play an important role in improving the sensitivity of mechanical resonating sensors. This is because the weight of the nanoparticle can increase the change in the resonance response of the mechanical sensor since this signal change is closely related to mass. Here, we introduce an experimental method to detect HBV at femtomolar concentrations using a silica nanoparticle-enhanced microcantilever resonating sensor. This method includes the preparation of detection probe-conjugated silica nanoparticles, immobilization of capture probe on the microcantilever sensor and sandwich type detection of HBV DNA. PMID- 22782827 TI - Protocol for the detection of Treponema pallidum in paraffin-embedded specimens. AB - Formalin-fixed paraffin-embedded (FFPE) tissue blocks are routinely used for histopathological examination and are also useful for specific pathogen detection by polymerase chain reaction (PCR). FFPE tissue is stable at ambient temperature for an extended period of time and relatively easy to transport compared to fresh tissue, which has to be processed or frozen immediately. In addition, archival material is an invaluable source for retrospective molecular and clinical investigation. This chapter describes detailed procedures for nucleic acid extraction and PCR detection of Treponema pallidum using FFPE tissue. PMID- 22782829 TI - Protocol for the molecular detection of antibiotic resistance mechanisms in Neisseria gonorrhoeae. AB - Gonorrhoea is no longer an easily treatable ailment but rather is now a challenging disease in terms of antimicrobial resistance (AMR) with treatment options rapidly diminishing. The causative agent of gonorrhoea, Neisseria gonorrhoeae, has managed to develop resistance to almost every single drug used against it with the sole exception of extended spectrum cephalosporins. The situation is further exacerbated by the fact that not only are the rates of gonococcal infections on a steady rise globally, but tracking AMR is being undermined by the growing popularity of molecular methods at the expense of traditional bacterial culture in diagnostic laboratories. Recently, concerns have been raised over the emergence of a multi-resistant gonococci and the potential for untreatable gonorrhoea. Maintaining optimal epidemiological surveillance of gonococcal AMR remains an important aspect of gonorrhoea control. The development of molecular tools for tracking AMR in N. gonorrhoeae has the potential to further enhance such surveillance. In this chapter, we discuss nucleic acid amplification-based detection of AMR in gonorrhoea with a particular emphasis on chromosomal-mediated resistance to beta-lactam antibiotics. PMID- 22782828 TI - Guidelines for the use of molecular biological methods to detect sexually transmitted pathogens in cases of suspected sexual abuse in children. AB - Testing for sexually transmitted infections (STIs) in children presents a number of problems for the practitioner that are not usually faced when testing adults for the same infections. The identification of an STI in a child, in addition to medical implications, can have serious legal implications. The presence of an STI is often used to support the presence or allegations of sexual abuse and conversely, the identification of an STI in a child will prompt an investigation of possible abuse. The significance of the identification of a sexually transmitted agent in such children as evidence of possible child sexual abuse varies by pathogen.While culture has historically been used for the detection of STIs in cases of suspected abuse in children, the increasing use of nucleic acid amplification tests (NAATs) in adults and the increasing proliferation of second generation tests with better sensitivity and specificity has made inroads into the use of such tests in children, especially for diagnostic and treatment purposes. Acceptance by the medicolegal system for sexual abuse cases is still controversial and more test cases will be necessary before definitive use becomes standard practice. In addition, if these assays ever become legally admissible in court, there will be recommendations that more than one NAAT assay be used in order to assure confirmation of the diagnostic result. PMID- 22782830 TI - Protocol for a facile multiplex PCR for multi-antimicrobial resistance and Gonococcus detection. AB - Gonorrhea is a continuing problem worldwide particularly in terms of the spread of multiple drug resistance. We have successfully developed an efficient PCR method for the simultaneous identification of gonococci and detection of the antimicrobial-resistant profile. By this method, penicillinase-producing Neisseria gonorrhoeae (PPNG), high-level tetracycline-resistant N. gonorrhoeae (TRNG), and ciprofloxacin-resistant N. gonorrhoeae (CRNG) can be clearly identified. Moreover, the plasmid-types of penicillin and tetracycline resistance are also characterized. The method has 100 % sensitivity and specificity. It is also time- and labor-saving compared to the conventional method. Thus, the procedure is suitable for epidemiological surveillance. PMID- 22782831 TI - Protocol for gene expression profiling using DNA microarrays in Neisseria gonorrhoeae. AB - Gene expression profiling using DNA microarrays has become commonplace in current molecular biology practices, and has dramatically enhanced our understanding of the biology of Neisseria spp., and the interaction of these organisms with the host. With the choice of microarray platforms offered for gene expression profiling and commercially available arrays, investigators must ask several central questions to make decisions based on their research focus. Are arrays on hand for their organism and if not then would it be cost-effective to design custom arrays. Other important considerations; what types of specialized equipment for array hybridization and signal detection are required and is the specificity and sensitivity of the array adequate for your application. Here, we describe the use of a custom 12K CombiMatrix ElectraSenseTM oligonucleotide microarray format for assessing global gene expression profiles in Neisseria spp. PMID- 22782832 TI - Protocol for analyzing human leukocyte antigen variants and sexually transmitted infections: from genotyping to immunoassays. AB - This chapter describes experimental and analytical procedures that can be used to decipher the specific role of human leukocyte antigen (HLA) variants in infectious diseases. The techniques are distilled from more than one decade of active immunogenetics research, primarily on sexually transmitted infections (STIs) caused by viral and bacterial pathogens, including human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), and Chlamydia trachomatis. The specific approaches cover (1) sequence-specific oligonucleotide (SSO) probe hybridization for low-resolution genotyping, (2) sequencing-based typing (SBT) for high-resolution, (3) statistical methods for testing associations between HLA variants and phenotypic traits, and (4) enzyme-linked immunospot (ELISpot) assay for enumerating HLA-restricted and epitope-specific T-lymphocyte responses. Proper application of these mature and robust techniques should help establish the importance of individual HLA alleles, haplotypes, and supertypes to host pathogen interactions. PMID- 22782833 TI - Protocol for the clonal analysis of NK cell effector functions by multi-parameter flow cytometry. AB - Natural killer (NK) cells provide a first line of defense against viral infections and prepare the ground for subsequent action of virus-specific T cells in a concerted way. Human NK cells use a sophisticated system of inhibitory and stimulatory receptors of the killer cell immunoglobulin-like receptor (KIR) gene family, which are expressed in a clonally distributed manner. Several studies suggest that KIR play a critical role in NK cell-mediated protection against HCV and HIV infection. As each NK cell expresses an individual set of KIR receptors that enables them to sense differences in HLA class I expression, classical measurement of NK cell function by analysis of target cell killing does not enable one to define and isolate the clinically relevant NK cell effector subsets. Here, we have developed a flow cytometry-based protocol to measure cytolytic activity together with KIR expression at a clonal level. Combined analysis of KIR expression in conjunction with cell surface mobilization of CD107 enables precise enumeration of cytolytic NK cells with defined specificity for HLA class I. Moreover, via inclusion of intracellular perforin or alternatively granzyme B, NK cells with deficient loading of cytotoxic granula can be identified. The present protocol enables identification and isolation of cytotoxic NK cells on a clonal level and enables reliable measurement in healthy as well as in pathological settings such as virus infection and hematological disease. PMID- 22782834 TI - Protocol for a mammalian cell-based assay for monitoring the HIV-1 protease activity. AB - Proteases are essential at different stages of the viral life cycle and for the establishment of a successful infection. Monitoring the catalytic activity of proteases in an easy and straightforward manner can thus drastically facilitate the discovery of novel antivirals, as well as help elucidate the activity and mechanism of action of the viral protease under study. In our laboratory, we have developed an assay in T-cells with a robust read-out to monitor the proteolytic activity of HIV-1 Protease (PR). The assay utilizes the prototypic transcription factor Gal4, which consists of the N-terminal DNA-binding domain and the C terminal trans-activation domain. The assay is based upon (1) introduction of PR in between the two Gal4 domains to obtain a PR/Gal4 fusion protein and (2) utilization of the enhanced Green Fluorescent Protein as reporter of PR activity.In order to overcome the possible cellular cytotoxicity of PR, the fusion protein in our assay is under the control of a tetracycline-inducible promoter. This ensures that it will be expressed only when needed, upon the addition of tetracycline or doxycycline. When active, PR has autocatalytic activity and cleaves itself from the Gal4 domains, resulting in the inability to induce eGFP expression. However, if PR activity is blocked or it is inactive, the two domains remain intact, resulting in eGFP expression. The assay can therefore be utilized to analyze the inhibitory effects of factors, peptides or compounds, designed on a rational- or nonrational-based approach, in the natural milieu of infection, where eGFP serves as a biosensor for PR activity. PMID- 22782835 TI - Self-collection of specimens for nucleic acid-based diagnosis of pharyngeal, cervicovaginal, urethral, and rectal Neisseria gonorrhoeae and Chlamydia trachomatis infections. AB - Commercially available nucleic acid amplification tests (NAATs) for Neisseria gonorrhoeae and Chlamydia trachomatis detection allow for self-collection including home-based collection from multiple anatomic sites such as the urethra, cervicovagina, rectum, and pharynx. Verification studies need to be done prior to processing pharyngeal and rectal specimens. We review specimen collection and test characteristics of NAATs at different anatomical sites. PMID- 22782836 TI - Sexually transmitted diseases: reflections on metaphors and ethics. AB - Sexually transmitted diseases (STDs) are probably the most tabooed diseases we know. The taboos and the related stigmata shape patients reality and influence significantly health care policies, medical research, and actual problems in medical ethics. To better understand these complex influences of ancient but still powerful taboos, related metaphors associated with illness and disease are analyzed according to their historical development and actual impact on society. It becomes obvious that research and health care policies cannot be satisfyingly successful in helping people affected by STDs as long as they do not take the mechanisms of taboos and associated metaphors into account. PMID- 22782837 TI - Age in relation to worker compensation costs in the construction industry. AB - BACKGROUND: A better understanding of how workers' compensation (WC) costs are affected by an aging US workforce is needed, especially for physically demanding industries, such as construction. METHODS: The relationship between age and injury type on claim costs was evaluated using a database of 107,064 Colorado WC claims filed between 1998 and 2008 among construction workers. RESULTS: Mean WC costs increased with increasing age for total cost (P < 0.0001), medical costs (P < 0.0001), and indemnity costs (P < 0.0001). For each one-year increase in age, indemnity, and medical costs increased by 3.5% and 1.1%, respectively. For specific injury types, such as strains and contusions, the association between age and indemnity costs was higher among claimants aged >=65 compared to claimants aged 18-24. CONCLUSIONS: Our findings suggest that specific injury types may be partially responsible for the higher indemnity costs among older construction workers, compared with their younger coworkers. PMID- 22782838 TI - The role of the basis set and the level of quantum mechanical theory in the prediction of the structure and reactivity of cisplatin. AB - In this article, we conducted an extensive ab initio study on the importance of the level of theory and the basis set for theoretical predictions of the structure and reactivity of cisplatin [cis-diamminedichloroplatinum(II) (cDDP)]. Initially, the role of the basis set for the Pt atom was assessed using 24 different basis sets, including three all-electron basis sets (ABS). In addition, a modified all-electron double zeta polarized basis set (mDZP) was proposed by adding a set of diffuse d functions onto the existing DZP basis set. The energy barrier and the rate constant for the first chloride/water exchange ligand process, namely, the aquation reaction, were taken as benchmarks for which reliable experimental data are available. At the B3LYP/mDZP/6-31+G(d) level (the first basis set is for Pt and the last set is for all of the light atoms), the energy barrier was 22.8 kcal mol(-1), which is in agreement with the average experimental value, 22.9 +/- 0.4 kcal mol(-1). For the other accessible ABS (DZP and ADZP), the corresponding values were 15.4 and 24.5 kcal mol(-1), respectively. The ADZP and mDZP are notably similar, raising the importance of diffuse d functions for the prediction of the kinetic properties of cDDP. In this article, we also analyze the ligand basis set and the level of theory effects by considering 36 basis sets at distinct levels of theory, namely, Hartree-Fock, MP2, and several DFT functionals. From a survey of the data, we recommend the mPW1PW91/mDZP/6-31+G(d) or B3PW91/mDZP/6-31+G(d) levels to describe the structure and reactivity of cDDP and its small derivatives. Conversely, for large molecules containing a cisplatin motif (for example, the cDDP-DNA complex), the lower levels B3LYP/LANL2DZ/6-31+G(d) and B3LYP/SBKJC-VDZ/6-31+G(d) are suggested. At these levels of theory, the predicted energy barrier was 26.0 and 25.9 kcal mol( 1), respectively, which is only 13% higher than the actual value. PMID- 22782839 TI - C-Glycosphingolipids with an exo-methylene substituent: stereocontrolled synthesis and immunostimulation of mouse and human natural killer T lymphocytes. PMID- 22782840 TI - Erratum to: The prevalence of HIV, HBV, HCV, and HIV-related risk-taking behaviors among Palestinian injecting drug users in the East Jerusalem Governorate. AB - The objective of the study was to determine HIV, HBV, HCV seroprevalence and to assess HIV risks among Palestinian injecting drug users (IDUs) in the East Jerusalem Governorate. Following formative research, a bio-behavioral survey using respondent-driven sampling was carried out in 2010 among 199 IDUs aged 19 56 years (M = 41.33, SD = 8.09). Venous blood was drawn for biological testing. Data on drug abuse and sexual behaviors were collected by face-to-face interviewing. No HIV + cases were found. Five participants were infected with Hepatitis B and 84 participants (estimated population proportion of 40.3%) tested positive for Hepatitis C. A great majority of the surveyed IDUs (90.4%) reported using sterile injecting equipment the last time they injected. In a multivariate assessment, age (OR = 2.52, p < .05), education (OR = 6.67, p < .01), personal network size (OR = .18, p < .001), and the frequency of drug injecting in the past month (OR = .20, p < .001) were associated with using sterile injecting equipment in the past week. Condom use at most recent sexual intercourse was reported by about a third (34.2%) of IDUs. The study documented substantial exposure to HIV risks among Palestinian IDUs whose vulnerability is inseparable from sociopolitic and socioeconomic characteristics of their social environment. PMID- 22782841 TI - Deoxygenation of coordinated oxaphosphiranes: a new route to P=C double-bond systems. PMID- 22782842 TI - Dramatic substituent effects on the photoluminescence of boron complexes of 2 (benzothiazol-2-yl)phenols. AB - Substituents can induce dramatic changes in the photoluminescence properties of N,O-chelated boron complexes. Specifically, the boron complexes of 2 (benzothiazol-2-yl)phenols become bright deep blue- and orange-red-emitting materials depending on amino substituents at the 5- and 4-positions of 2 (benzothiazol-2-yl)phenol, respectively. Absorption and emission data show that the resulting boron complexes have little or small overlap between the absorption and emission spectra and, furthermore, X-ray crystal structures for both the blue and orange-red complexes indicate the absence of pi-pi stacking interaction in the crystal-packing structures. These features endow the boron complexes with bright and strong photoluminescence in the solid state, which distinguishes itself from the typical boron complexes of dipyrromethenes (BODIPYs). A preliminary study indicates that the blue complexes have promising electro optical characteristics as dopant in an organic light-emitting diode (OLED) device and show chromaticity close to an ideal deep blue. The substituent effects on the photoluminescent properties may be used to tune the desired emission wavelength of related boron or other metal complexes. PMID- 22782844 TI - Flow diversion to treat aneurysms: the free segment of stent. AB - PURPOSE: Flow diverters (FDs) have led to spectacular results in otherwise untreatable aneurysm cases, but complications can occur. There is a pressing need to study factors that might predict their safety and efficacy. METHODS: The anatomical constraints that may impact on the ability of FDs to redirect blood flow and provide a scaffold for neointima formation across the aneurysm or branch ostia are explored and classified. A nomenclature is needed to identify the key factors that should be taken into account before contemplating the use of FDs in clinical aneurysms, and that should be reproduced in experimental models, if they are to guide safe clinical use. RESULTS: The free stent segment (FSS), the portion of the device that covers an aneurysm or branch origin, dictates whether aneurysms or branches will remain patent. Three levels of increasing complexity must be taken into account to anticipate what will occur at the FSS level. (1) Virtual models can provide basic principles; (2) in vitro studies allow testing FSS deformations that may occur in various anatomical circumstances and impact on efficacy and safety; (3) but only in vivo studies can provide key information on neointimal closure following implantation that will differentiate success from failure. CONCLUSIONS: A nomenclature is necessary to determine the optimal or suboptimal conditions for FDs and to design the virtual, in vitro and in vivo studies that will allow a better understanding of the factors involved in the success or failure of this novel treatment. PMID- 22782845 TI - Binding energies of five molecular pincers calculated by explicit and implicit solvent models. AB - Molecular pincers or tweezers are designed to hold and release the target molecule. Potential applications involve drug distribution in medicine, environment technologies, or microindustrial techniques. Typically, the binding is dominated by van der Waals forces. Modeling of such complexes can significantly enhance their design; yet obtaining accurate complexation energies by theory is difficult. In this study, density functional theory (DFT) computations combined with dielectric continuum solvent model are compared with the potential of mean force approach using umbrella sampling and the weighted histogram analysis method (WHAM) with molecular dynamics (MD) simulations. For DFT, functional and basis set effects are discussed. The computed results are compared to experimental data based on NMR spectroscopic measurements of five synthesized tweezers based on the Troger's basis. Whereas the DFT computations correctly provided the observed trends in complex stability, they failed to produce realistic magnitudes of complexation energies. Typically, the binding was overestimated by DFT if compared to experiment. The simpler semiempirical PM6 DH2X scheme proposed lately yielded better magnitudes of the binding energies than DFT but not the right order. The MD-WHAM simulations provided the most realistic Gibbs binding energies, although the approximate MD force fields were not able to reproduce completely the ordering of relative stabilities of model complexes found by NMR. Yet the modeling provides interesting insight into the complex geometry and flexibility and appears as a useful tool in the tweezers' design. PMID- 22782846 TI - Hexafluoroisopropanol: a powerful solvent for the hydrogenation of indole derivatives. Selective access to tetrahydroindoles or cis-fused octahydroindoles. AB - Pd/C in HFIP was used to hydrogenate indole derivatives under relatively mild conditions, leading to potential synthetic intermediates of bioactive compounds. Depending on their substitution, tetrahydroindoles or octahydroindoles could selectively be obtained. PMID- 22782847 TI - Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study. AB - OBJECTIVE: To analyse the association between alcohol intake and incidence of rheumatoid arthritis in women. DESIGN: Prospective cohort study with repeated measurements. SETTING: The Swedish Mammography Cohort, a population based cohort from central Sweden. PARTICIPANTS: 34,141 women born between 1914 and 1948, followed up from 1 January 2003 to 31 December 2009. MAIN OUTCOME MEASURES: Newly diagnosed cases of rheumatoid arthritis identified by linkage with two Swedish national registers. Data on alcohol consumption were collected in 1987 and 1997. RESULTS: During the follow-up period (226,032 person years), 197 incident cases of rheumatoid arthritis were identified. There was a statistically significant 37% decrease in risk of rheumatoid arthritis among women who drank >4 glasses of alcohol (1 glass = 15 g of ethanol) per week compared with women who drank <1 glass per week or who never drank alcohol (relative risk 0.63 (95% confidence interval 0.42 to 0.96), P = 0.04). Drinking of all types of alcohol (beer, wine, and liquor) was non-significantly inversely associated with the risk of rheumatoid arthritis. Analysis of long term alcohol consumption showed that women who reported drinking >3 glasses of alcohol per week in both 1987 and 1997 had a 52% decreased risk of rheumatoid arthritis compared with those who never drank (relative risk 0.48 (0.24 to 0.98)). CONCLUSION: Moderate consumption of alcohol is associated with reduced risk of rheumatoid arthritis. PMID- 22782849 TI - Quitting smoking and gaining weight: the odd couple. PMID- 22782850 TI - Interfacial electron transfer from CdSe/ZnS quantum dots to TiO2 nanoparticles: size dependence at the single-molecule level. AB - Electron transfer (ET) kinetics of CdSe/ZnS core/shell quantum dots (QDs) on bare coverslips and a TiO(2) nanoparticle-coated thin film has been investigated at the single-molecule level. The QDs prepared have three different diameters of 3.6, 4.6, and 6.4 nm. The trajectories of fluorescence intensity are acquired with respect to the arrival time. The on-time events and subsequent fluorescence lifetimes are shorter with decreasing size. Given the lifetime measurements for QDs on glass and TiO(2), the rate constant of ET from QDs to TiO(2) may be determined to be 1.3*10(7), 6.0*10(6), and 4.7*10(6) s(-1) for the increasing sizes of the QDs. The plot of on-time probability density versus arrival time is characterized by power-law statistics in the short time region and a bending tail in the long time region. Marcus's ET model is employed to satisfactorily fit the bending tail behavior and to further calculate the ET rate constants. The theoretical counterparts for the different sizes are 1.4*10(7), 6.4*10(6), and 1.9*10(6) s(-1), showing good agreement with the experimental results. PMID- 22782848 TI - Weight gain in smokers after quitting cigarettes: meta-analysis. AB - OBJECTIVE: To describe weight gain and its variation in smokers who achieve prolonged abstinence for up to 12 months and who quit without treatment or use drugs to assist cessation. DESIGN: Meta-analysis. DATA SOURCES: We searched the Central Register of Controlled Trials (CENTRAL) and trials listed in Cochrane reviews of smoking cessation interventions (nicotine replacement therapy, nicotinic partial agonists, antidepressants, and exercise) for randomised trials of first line treatments (nicotine replacement therapy, bupropion, and varenicline) and exercise that reported weight change. We also searched CENTRAL for trials of interventions for weight gain after cessation. REVIEW METHODS: Trials were included if they recorded weight change from baseline to follow-up in abstinent smokers. We used a random effects inverse variance model to calculate the mean and 95% confidence intervals and the mean of the standard deviation for weight change from baseline to one, two, three, six, and 12 months after quitting. We explored subgroup differences using random effects meta-regression. RESULTS: 62 studies were included. In untreated quitters, mean weight gain was 1.12 kg (95% confidence interval 0.76 to 1.47), 2.26 kg (1.98 to 2.54), 2.85 kg (2.42 to 3.28), 4.23 kg (3.69 to 4.77), and 4.67 kg (3.96 to 5.38) at one, two, three, six, and 12 months after quitting, respectively. Using the means and weighted standard deviations, we calculated that at 12 months after cessation, 16%, 37%, 34%, and 13% of untreated quitters lost weight, and gained less than 5 kg, gained 5-10 kg, and gained more than 10 kg, respectively. Estimates of weight gain were similar for people using different pharmacotherapies to support cessation. Estimates were also similar between people especially concerned about weight gain and those not concerned. CONCLUSION: Smoking cessation is associated with a mean increase of 4-5 kg in body weight after 12 months of abstinence, and most weight gain occurs within three months of quitting. Variation in weight change is large, with about 16% of quitters losing weight and 13% gaining more than 10 kg. PMID- 22782851 TI - Concise review: chromatin and genome organization in reprogramming. AB - The ability to reprogram somatic cells to pluripotency is continuingly attracting increasing amounts of attention, providing both potential opportunities for regenerative medicine, as well as an intriguing model to study basic mechanisms of developmental reversal and epigenetic erasure. Currently, nuclear reprogramming is an inefficient process and a better understanding of its components and the underlying mechanisms will no doubt enable us to increase its robustness and to gain a deeper understanding of its regulation. Here we focus on the reprogramming process from the chromatin and genome organization perspective, describing the chromatin changes that occur both globally and locally. At the global level, chromatin decondenses toward the characteristic 'open' state, while locally, chromatin reorganization supports the silencing of lineage-specific genes and the activation of pluripotency-related genes. Importantly, the proteins that regulate this process are being identified, revealing different layers of chromatin regulation, including histone modifications, histone variants, chromatin remodeling and genomic DNA methylation. The emerging theme is that chromatin and genome organization are not only altered during the transition from a somatic to a pluripotent state, but also play active, regulatory roles during the reprogramming process. PMID- 22782852 TI - Expression patterns of cancer stem cell markers ALDH1 and CD133 correlate with a high risk of malignant transformation of oral leukoplakia. AB - Molecular markers for predicting oral cancer development in premalignant oral leukoplakia (OL) are urgently needed. The objective of this study was to examine the expression patterns of cancer stem cell markers ALDH1 and CD133 in samples from patients with OL, and determine their prognostic values for subsequent development of oral cancer. Immunohistochemistry for ALDH1 and CD133 was performed in samples from a cohort of 141 patients with biopsy-proven OL who received a mean follow-up of 5.5 years. Patient clinicopathologic and follow-up data were analyzed. Expression of ALDH1 and CD133 was observed in 54 (38.3%) and 32 (22.7%) of 141 patients with OL, respectively. Kaplan-Meier analysis showed that 48.1% patients with ALDH1-positivity developed oral cancer compared with 12.6% those with ALDH1-negativity (p < 0.001). Meanwhile, 59.4% patients with CD133-positivity developed oral cancer compared with 16.5% those with CD133 negativity (p < 0.001). Multivariate analysis revealed that ALDH1 and CD133 expression was associated with 4.17-fold [95% confidence interval (CI), 1.96 8.90; p < 0.001] and 2.86-fold (95% CI, 1.48-5.55; p = 0.002) increased risk of OL transformation, respectively. Collectively, these data demonstrated for the first time that the expression of ALDH1 and CD133 correlated with malignant transformation in a large series of patients with OL who received a long-term follow-up, which suggests that they may serve as predictors to identify OL with a high risk of oral cancer development. PMID- 22782853 TI - Interfacial synthesis and functionality of self-stabilized polydiaminonaphthalene nanoparticles. AB - A simple and effective template-free synthesis method for nanosized conducting polymers with self-stability and functionality is a main challenge. Herein, a strategy is reported for the facile synthesis of poly(1,5-diaminonaphthalene) nanospherical particles by an interfacial miniemulsion oxidative polymerization of 1,5-diaminonaphthalene at mobile microinterfaces between a stirred biphase without external emulsifiers. The size of the nanospheres was carefully optimized by controlling the polymerization conditions. Formation and self-stabilization mechanisms of the nanoparticles are proposed. The constantly movable and refreshed microinterface is a key to successful synthesis of the nanospheres, for significantly suppressing secondary growth leading to agglomerated particles because vigorous stirring makes as-formed self-stabilized nanospheres instantly leave the microinterfaces. The resulting nanospheres possess several advantages: clean surface, self-stability, redispersibility, semiconductivity, electroactivity, and fluorescence emission. The fluorescence emission can be quenched by specific quenchers, thus enabling low-cost, high-performance chemosensors to be obtained for the sensitive detection of Zn(II) ions in a wide linear concentration range of more than five orders of magnitude with a superior detection limit down to 1 nM. PMID- 22782854 TI - Bivalent enzyme inhibitors discovered using dynamic covalent chemistry. AB - A bivalent dynamic covalent chemistry (DCC) system has been designed to selectively target members of the homodimeric glutathione-S-transferase (GST) enzyme family. The dynamic covalent libraries (DCLs) use aniline-catalysed acylhydrazone exchange between bivalent hydrazides and glutathione-conjugated aldehydes and the bis-hydrazides act as linkers to bridge between each glutathione binding site. The resultant DCLs were found to be compatible and highly responsive to templating with different GST isozymes, with the best results coming from the M and Schistosoma japonicum (Sj) class of GSTs, targets in cancer and tropical disease, respectively. The approach yielded compounds with selective, nanomolar affinity (K(i) =61 nM for mGSTM1-1) and demonstrates that DCC can be used to simultaneously interrogate binding sites on different subunits of a dimeric protein. PMID- 22782855 TI - Dry-wet cycles increase pesticide residue release from soil. AB - Soil drying and rewetting may alter the release and availability of aged pesticide residues in soils. A laboratory experiment was conducted to evaluate the influence of soil drying and wetting on the release of pesticide residues. Soil containing environmentally long-term aged (9-17 years) (14) C-labeled residues of the herbicides ethidimuron (ETD) and methabenzthiazuron (MBT) and the fungicide anilazine (ANI) showed a significantly higher release of (14) C activity in water extracts of previously dried soil compared to constantly moistened soil throughout all samples (ETD: p < 0.1, MBT and ANI: p < 0.01). The extracted (14) C activity accounted for 44% (ETD), 15% (MBT), and 20% (ANI) of total residual (14) C activity in the samples after 20 successive dry-wet cycles, in contrast to 15% (ETD), 5% (MBT), and 6% (ANI) in extracts of constantly moistened soils. In the dry-wet soils, the dissolved organic carbon (DOC) content correlated with the measured (14) C activity in the aqueous liquids and indicated a potential association of DOC with the pesticide molecules. Liquid chromatography MS/MS analyses of the water extracts of dry-wet soils revealed ETD and MBT in detectable amounts, accounting for 1.83 and 0.01%, respectively, of total applied water-extractable parent compound per soil layer. These findings demonstrate a potential remobilization of environmentally aged pesticide residue fractions from soils due to abiotic stresses such as wet-dry cycles. PMID- 22782857 TI - A new glimpse into the CO(2)-philicity of carbonyl compounds. AB - We report a theoretical study on non-conventional structures of 1:1 complexes between carbon dioxide and carbonyl compounds. These structures have never been reported before but are relevant for understanding the solubility of carbonyl compounds in supercritical CO(2). The work is based on the results of ab initio calculations at the MP2 and CCSD(T) levels using aug-cc-pVDZ and aug-cc-pVTZ basis sets. Investigated systems include aldehydes, ketones and esters, together with some fluorinated derivatives. The results are interpreted in terms of natural bond orbital analyses. Harmonic vibrational frequency calculations have also been done in order to compare them with available experimental data. We show for the first time that complexes where CO(2) behaves globally as a Lewis base are stable in the case of ketones and esters, but not in the case of aldehydes, and their stability is similar to that of traditional complexes in which CO(2) behaves as a Lewis acid. This finding considerably modifies the concept of CO(2) philicity and may have important ramifications in the development of green reactions in supercritical CO(2). PMID- 22782856 TI - Potential metabolomic biomarkers for evaluation of adriamycin efficacy using a urinary 1H-NMR spectroscopy. AB - A metabolomics approach using proton nuclear magnetic resonance (NMR) was applied to investigate metabolic alterations following adriamycin (ADR) treatment for gastric adenocarcinoma. After BALB/c-nu/nu mice were implanted with human gastric adenocarcinoma, ADR (1 or 3 mg kg(-1) per day) was intraperitoneally administered for 5 days. Urine was collected on days 2 and 5 and analyzed by NMR. The levels of trimethylamine oxide (TMAO, *0.3), hippurate (*0.3) and taurine (*0.6) decreased significantly (P < 0.05), whereas the levels of 3-indoxylsulfate (*12.6), trigonelline (*1.5), citrate (*2.5), trimethylamine (TMA, *2.0) and 2 oxoglutarate (*2.3) increased significantly (P < 0.05) in the tumor model. After ADR treatment, TMAO, hippuarte and taurine were increased significantly on day 5 compared with those of the tumor model. The levels of 2-oxoglutarate, 3 indoxylsulfate, trigonelline, TMA and citrate, which increased in the tumor model, significantly decreased to those of normal control by ADR treatment. Furthermore, the ratio between TMA and TMAO was dramatically altered in both tumor and ADR-treated groups. Overall, metabolites such as TMAO, TMA, 3 indoxylsulfate, hippurate, trigonelline, citrate and 2-oxoglutarate related to the tricarboxylic acid (TCA) cycle might be considered as therapeutic targets to potentiate the efficacy of ADR. Thus, these results suggest that the metabolomics analysis of tumor response to ADR treatment may be applicable for demonstrating the efficacy of anticancer agent, ADR and treatment adaptation. PMID- 22782858 TI - Tumor-initiating cells of various tumor types exhibit differential angiogenic properties and react differently to antiangiogenic drugs. AB - Tumor-initiating cells (TICs) are a subtype of tumor cells believed to be critical for initiating tumorigenesis. We sought to determine the angiogenic properties of TICs in different tumor types including U-87MG (glioblastoma), HT29 (colon), MCF7 (breast), A549 (non-small-cell lung), and PANC1 (pancreatic) cancers. Long-term cultures grown either as monolayers ("TIC-low") or as nonadherent tumor spheres ("TIC-high") were generated. The TIC-high fractions exhibited increased expression of stem cell surface markers, high aldehyde dehydrogenase activity, high expression of p21, and resistance to standard chemotherapy in comparison to TIC-low fractions. Furthermore, TICs from U-87MG and HT29 but not from MCF7, A549, and PANC1 tumor types possess increased angiogenic activity. Consequently, the efficacy of vascular endothelial growth factor-A (VEGF-A) neutralizing antibody is limited only to those tumors that are dependent on VEGF-A activity. In addition, such therapy had little or reversed antiangiogenic effects on tumors that do not necessarily rely on VEGF-dependent angiogenesis. Differential angiogenic activity and antiangiogenic therapy sensitivity were also observed in TICs of the same tumor type, suggesting redundant angiogenic pathways. Collectively, our results suggest that the efficacy of antiangiogenic drugs is dependent on the angiogenic properties of TICs and, therefore, can serve as a possible biomarker to predict antiangiogenic treatment efficacy. PMID- 22782859 TI - Atomic polarizability dominates the electronic properties of peptide bonds upon thioxo or selenoxo substitution. AB - The amide bond as peptide linkage plays an important role in protein structure and function. A large number of theoretical and experimental studies have focused on the specific nature of the peptide bond. Little attention, however, has been paid to their chalcogen-substituted congeners, although experimental data on thioamides revealed inconsistencies with the conventional view of amide resonance theory. Here, we employed thioxo and selenoxo substitution to determine experimentally how heavier chalcogens affect the properties of the peptide bond and adjacent atoms. NMR data revealed pronounced deshielding of heteronuclei within a three-bond distance to the chalcogen atom; this indicates an enhanced electron-withdrawing potential of the heavier chalcogens despite their lower electronegativities compared to oxygen. Interestingly, linear correlations were observed between chalcogen atomic polarizability and the chemical shift values of those neighboring heteronuclei as well as several physicochemical properties, such as electronic excitation energy, C-N rotation barrier, dipole moment and amide proton dissociation. We conclude that the chalcogen polarizability, which relates to the charge capacity, is the dominant factor that determines the electronic properties of peptide bonds substituted with heavier chalcogens. PMID- 22782860 TI - Cooperative switching events in azobenzene foldamer denaturation. AB - Insight into the mechanism of photoswitchable foldamer denaturation was gained by incorporating two azobenzene switching units (see figure; orange) into the helix backbone. Optimizing the location of the units leads to cooperative photoisomerization events, causing complete unfolding. The switching cooperativity coupled with the cooperative unfolding transition enables the design of highly photosensitive systems. PMID- 22782861 TI - Automated double red-cell phlebotomy for the treatment of erythrocytosis. AB - BACKGROUND: Phlebotomy has been used as a primary method for the treatment of erythrocytosis. As a new phlebotomy method, we used an automated component collection system (Alyx, Fenwal), which has been used to obtain two units of leukoreduced red blood cells (RBCs) from donors. We evaluated the effectiveness of "double red-cell" phlebotomy (DRP) and compared it with conventional "whole blood" phlebotomy (WBP). MATERIALS AND METHODS: We have performed a total of 596 phlebotomies in 158 patients with erythrocytosis between June 2008 and November 2011. Forty patients underwent 84 DRPs and 118 patients underwent 512 WBPs. We removed 360-420 mL of RBCs in DRP and 360-600 mL of whole blood in WBP according to patient's total blood volume (TBV). Changes in hematologic parameters after phlebotomy were compared. RESULTS: DRP removed more RBC volume (399.4 +/- 20.2 mL vs. 235.9 +/- 29.8 mL, P < 0.05) and lowered more hematocrit than WBP (6.9% +/- 2.3% vs. 3.0% +/- 1.7%, P < 0.05). Hematocrit reduction per kilogram of body weight was higher by DRP than WBP (0.106% +/- 0.043% vs. 0.039% +/- 0.025%, P < 0.05). Mild adverse events occurred in 32.5% (13/40) during DRP and 4.2% (5/118) during WBP. CONCLUSION: DRP lowered more RBC mass than WBP by selectively removing more RBC volume with less TBV. DRP can be an effective and safe technique for the treatment of erythrocytosis. PMID- 22782862 TI - Evolution in response to climate change: in pursuit of the missing evidence. AB - Climate change is imposing intensified and novel selection pressures on organisms by altering abiotic and biotic environmental conditions on Earth, but studies demonstrating genetic adaptation to climate change mediated selection are still scarce. Evidence is accumulating to indicate that both genetic and ecological constrains may often limit populations' abilities to adapt to large scale effects of climate warming. These constraints may predispose many organisms to respond to climate change with range shifts and phenotypic plasticity, rather than through evolutionary adaptation. In general, broad conclusions about the role of evolutionary adaptation in mitigating climate change induced fitness loss in the wild are as yet difficult to make. PMID- 22782863 TI - Lysophosphatidic acid induces migration of human lung-resident mesenchymal stem cells through the beta-catenin pathway. AB - Mesenchymal stem cells (MSCs) have been demonstrated to reside in human adult organs. However, mechanisms of migration of these endogenous MSCs within their tissue of origin are not well understood. Here, we investigate migration of human adult lung-resident (LR) mesenchymal progenitor cells. We demonstrate that bioactive lipid lysophosphatidic acid (LPA) plays a principal role in the migration of human LR-MSCs through a signaling pathway involving LPA1-induced beta-catenin activation. LR-MSCs isolated from human lung allografts and lungs of patients with scleroderma demonstrated a robust migratory response to LPA in vitro. Furthermore, LPA levels correlated with LR-MSC numbers in bronchoalveolar lavage (BAL), providing demonstration of the in vivo activity of LPA in human adult lungs. Migration of LR-MSCs was mediated via LPA1 receptor ligation and LPA1 silencing significantly abrogated the migratory response of LR-MSCs to LPA as well as human BAL. LPA treatment of LR-MSCs induced protein kinase C-mediated glycogen synthase kinase-3beta phosphorylation, with resulting cytoplasmic accumulation and nuclear translocation of beta-catenin. TCF/LEF dual luciferase gene reporter assay demonstrated a significant increase in transcriptional activity after LPA treatment. LR-MSC migration and increase in reporter gene activity in the presence of LPA were abolished by transfection with beta-catenin small interfering RNA demonstrating that beta-catenin is critical in mediating LPA-induced LR-MSC migration. These data delineate a novel signaling pathway through which ligation of a G protein-coupled receptor by a biologically relevant lipid mediator induces migration of human tissue-resident mesenchymal progenitors. PMID- 22782865 TI - Occupation and (social) class refer to different social mechanisms. PMID- 22782864 TI - Paternal occupation and birth defects: findings from the National Birth Defects Prevention Study. AB - OBJECTIVES: Several epidemiological studies have suggested that certain paternal occupations may be associated with an increased prevalence of birth defects in offspring. Using data from the National Birth Defects Prevention Study, the authors investigated the association between paternal occupation and birth defects in a case-control study of cases comprising over 60 different types of birth defects (n=9998) and non-malformed controls (n=4066) with dates of delivery between 1997 and 2004. METHODS: Using paternal occupational histories reported by mothers via telephone interview, jobs were systematically classified into 63 groups based on shared exposure profiles within occupation and industry. Data were analysed using bayesian logistic regression with a hierarchical prior for dependent shrinkage to stabilise estimation with sparse data. RESULTS: Several occupations were associated with an increased prevalence of various birth defect categories, including mathematical, physical and computer scientists; artists; photographers and photo processors; food service workers; landscapers and groundskeepers; hairdressers and cosmetologists; office and administrative support workers; sawmill workers; petroleum and gas workers; chemical workers; printers; material moving equipment operators; and motor vehicle operators. CONCLUSIONS: Findings from this study might be used to identify specific occupations worthy of further investigation and to generate hypotheses about chemical or physical exposures common to such occupations. PMID- 22782866 TI - Pectin methyl esterase treatment on high-methoxy pectin for making fruit jam with reduced sugar content. AB - BACKGROUND: Pectin methyl esterase (PME) has been postulated to catalyse the transacylation reaction between pectin molecules. The present study aimed to prove the occurrence of this reaction. The feasibility of applying PME-catalysed transacylation between high-methoxy pectin molecules in making fruit jam with reduced sugar content was also investigated. RESULTS: PME treatment increased the turbidity and particle size in pectin solution and the molecular weight of pectin, while it decreased the number of methoxy ester linkages and the intensity of the CH3 absorption peak in the Fourier transform infrared spectrum without changes in the number of total ester linkages in pectin molecules. These findings support the occurrence of PME-catalysed transacylation between pectin molecules. Higher values of hardness, gumminess and chewiness were found in a jam containing PME-treated citrus pectin (10 g L-1) and sugar (350 g L-1) as compared with either a jam containing untreated citrus pectin (10 g L-1) and sugar (350 g L-1) or strawberry jam containing pectin (10 g L-1) from the fruit and sugar (650 g L 1). CONCLUSION: The demand for sugar in jam making can be greatly reduced by the use of PME-treated high-methoxy pectin. PMID- 22782867 TI - Symmetry-enthalpy correlations in Diels-Alder reactions. AB - Woodward-Hoffmann (WH) rules provide strict symmetry selection rules: when they are obeyed, a reaction proceeds; when they are not obeyed, there is no reaction. However, the voluminous experimental literature provides ample evidence that strict compliance to symmetry requirements is not an obstacle for a concerted reaction to proceed, and therefore the idea has developed that it is enough to have a certain degree of the required symmetry to have reactivity. Here we provide quantitative evidence of that link, and show that as one deviates from the desired symmetry, the enthalpy of activation increases, that is, we show that concerted reactions slow down the further they are from the ideal symmetry. Specifically, we study the deviation from mirror symmetry (evaluated with the continuous symmetry measure (CSM)) of the [4+2] carbon skeleton of the transition state of a series of twelve Diels-Alder reactions in seven different solvents (and in the gas phase), in which the dienes are butadiene, cyclopentadiene, cyclohexadiene, and cycloheptadiene; the dienophiles are the 1-, 1,1-, and 1,1,2 cyanoethylene derivatives; the solvents were chosen to sample a range of dielectric constants from heptane to ethanol. These components provide twenty four symmetry-enthalpy DFT-calculated correlation lines (out of which only one case is a relatively mild exception) that show the general trend of increase in enthalpy as symmetry decreases. The various combinations between the dienophiles, cyanoethylenes, and solvents provide all kinds of sources for symmetry deviations; it is therefore remarkable that although the enthalpy of activation is dictated by various parameters, symmetry emerges as a primary parameter. In our analysis we also bisected this overall picture into solvent effects and geometry variation effects to evaluate under which conditions the electronic effects are more dominant than symmetry effects. PMID- 22782868 TI - Stereocontrolled total synthesis of (+)-trans-dihydronarciclasine. AB - A highly stereoselective and efficient total synthesis of trans dihydronarciclasine from a readily available chiral starting material was developed. The synthesis defines two of the five stereogenic centers of the natural product by an amino acid ester-enolate Claisen rearrangement. The other three stereogenic centers are created in a highly stereocontrolled fashion via a six-ring vinylogous ester intermediate, which is generated from the gamma,delta unsaturated ester functional group of the Claisen rearrangement product in an efficient three-step sequence. This concise total synthesis exemplifies the use of a highly regioselective Friedel-Crafts-type cyclization to form the B ring via an isocyanate intermediate derived from an N-Boc group, which is superior to the conventional method using an imino triflate intermediate. This same N-Boc group is employed to give high selectivity in the Claisen rearrangement earlier in the sequence. PMID- 22782869 TI - Abstracts of the 42nd Annual Meeting of the International Continence Society (ICS), 15 - 19 October 2012, Beijing, China. PMID- 22782870 TI - Characterization of the prostate cancer susceptibility gene KLF6 in human and mouse prostate cancers. AB - BACKGROUND: Kruppel-like factor (KLF) 6 is a candidate tumor suppressor gene in prostate cancer, but the mechanisms contributing to its loss of expression are poorly understood. We characterized KLF6 expression and DNA methylation status during prostate tumorigenesis in humans and mice. METHODS: KLF6 expression was assessed in matched human non-malignant (NM) and tumor prostate tissues (n = 22) by quantitative real-time PCR (qPCR) and in three independent human prostate cancer cohorts bioinformatically. QPCR for KLF6 expression and methylation sensitive PCR (MSP) were performed in human prostate LNCaP cancer cells after 5 aza-2'-deoxycytidine treatment. Klf6 protein levels and DNA promoter methylation were assessed in TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) tumors by immunohistochemistry and MSP, respectively. RESULTS: KLF6 splice variants expression was increased (P = 0.0015) in human prostate tumors compared to NM tissues. Overall, KLF6 was decreased in metastatic compared to primary prostate cancers and reduced expression in primary tumors was associated with a shorter time to relapse (P = 0.0028). Treatment with the demethylating agent 5-aza-2' deoxycytidine resulted in up-regulation of KLF6 expression (two-fold; P = 0.002) and a decrease in DNA methylation of the KLF6 promoter in LNCaP cells. Klf6 protein levels significantly decreased with progression in the TRAMP model of prostate cancer (P < 0.05), but there was no difference in Klf6 promoter methylation. CONCLUSION: KLF6 expression was decreased in both clinical prostate cancer and the TRAMP model with disease progression, but this could not be explained by DNA methylation of the KLF6 promoter. PMID- 22782871 TI - Glycosidic inhibitors of melanogenesis from leaves of Momordica charantia. AB - Eight glycosidic compounds, 1-8, including two new compounds, (4xi)-alpha terpineol 8-O-[alpha-L-arabinopyranosyl-(1->6)-beta-D-glucopyranoside] (5) and myrtenol 10-O-[beta-D-apiofuranosyl-(1->6)-beta-D-glucopyranoside] (7), were isolated from the BuOH-soluble fraction of a MeOH extract of Momordica charantia leaves. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of compounds 1-8 on the melanogenesis in B16 melanoma cells induced with alpha melanocyte-stimulating hormone (alpha-MSH), these compounds were found to exhibit inhibitory activities with 7.1-27.0% and 23.6-46.4% reduction of melanin content at 30 MUM and 100 MUM, respectively, with no or almost no toxicity to the cells (80.0-103.5% of cell viability at 100 MUM). Western blot analysis showed that compound 7 reduced the protein levels of MITF, tyrosinase, TRP-1, and TRP-2 mostly in a concentration-dependent manner, suggesting that this compound inhibits melanogenesis on the alpha-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of tyrosinase, TRP-1, and TRP-2. PMID- 22782872 TI - Brain pharmacokinetics of non-imidazole biphenyl H3 receptor antagonists: a liquid chromatography/electrospray-mass spectrometry and ex vivo binding study in rats. AB - In the present article, we report on the kinetics of brain penetration in rats of the H3R antagonist 1,1'-[1,1'-biphenyl-4,4'-diylbis(methylene)]bis-[piperidine] (1), which had shown a favorable in vitro pharmacological profile and in vivo potency in preventing scopolamine-induced amnesia. Two different approaches were employed: high-performance liquid chromatography/electrospray-mass spectrometry (HPLC/ESI-MS) and ex vivo binding against the labeled agonist [(3)H]-(R)-alpha methylhistamine ([(3)H]RAMHA). Starting from the structure of 1, the rigid piperidine ring was replaced by a flexible dipropylamino group (see 2) or by a morpholino ring (see 3), endowed with lower basicity. The effect of replacement on rat plasma and brain disposition in the 24 h after administration was analyzed. High (MUM) and persistent concentrations of 1 were found in rat plasma, while plasma levels were significantly lower (range: 0-200 nM) for the other two derivatives. This could be explained, among other factors, by the higher stability, observed for 1, to liver metabolic cleavage. The applied chemical modulation had an important effect on in vivo brain disposition, as, despite the comparable physico-chemical properties, 2 did not show the tendency to accumulate within the brain, as stated by its brain vs. plasma concentration ratios, if compared to 1. These structure?property relationships should be taken into account in the pharmacokinetic optimization of new series of H3 receptor antagonists. PMID- 22782873 TI - The influence of the substitution pattern on the molecular conformation of ureido 1,2,5-oxadiazoles, related to STAT3 inhibitors: chemical behavior and structural investigation. AB - Signal transducer and activator of transcription 3 (STAT3) is a protein constitutively activated by aberrant upstream tyrosine kinase activities in a broad spectrum of human solid and blood tumors. Therefore, the availability of drugs affecting STAT3 may have important therapeutic potential for the treatment of cancer. Pursuing our efforts in exploring the influence of the substitution pattern of the ureido 1,2,5-oxadiazole moiety on the molecular conformation, new compounds substituted at positions 3 and 4 on the furazane ring were synthesized. The inhibition properties vs. STAT3 of the novel compounds were evaluated in a dual-luciferase assay, using HCT-116 cells, and the results evidenced a moderate activity only for the compounds endowed with a planar arrangement. Crystallographic studies of the new derivatives were performed in order to evidence the peculiar chemical behavior and to evaluate how structural modulations affected the biological properties. PMID- 22782874 TI - Chemical classification of the essential oils of the Iranian Salvia species in comparison with their botanical taxonomy. AB - The essential oils of eight Salvia species collected from different localities in Iran were analyzed by gas chromatography/mass spectrometry (GC/MS). The analytical results were compared with those previously published for related Iranian sage species in order to identify chemical markers for these species. Salvia eremophila, S. hypoleuca, and S. reuteriana are endemic, while S. atropatana, S. chloroleuca, S. santolinifolia, S. aegyptiaca, and S. macrosiphon also grow wild in neighboring countries. We categorized the Iranian Salvia species into four main chemotypes according to their essential-oil constituents: those which are dominated by 1) monoterpenes, 2) mono- and sesquiterpenes, or 3) sesquiterpenes as the major constituents, and 4) those containing low-molecular weight acids, aldehydes, and esters, and green-leaf volatiles (GLVs). Likely due to the chemical diversity of different Salvia chemotypes, this categorization was supported by principal component analysis (PCA) for the group sampled here, but not for the values reported in the literature. We identified the following chemical markers: alpha-pinene, beta-pinene, 1,8-cineol, linalool, and borneol in monoterpene-rich species, or beta-caryophyllene, germacrene D, bicyclogermacrene, spathulenol, and caryophyllene oxide in sesquiterpene-rich species. Among these, alpha-pinene, beta-caryophyllene, and germacrene D are the most common and abundant in the Salvia species investigated. In accordance with their close biological taxonomy, the chemical similarity of the essential oils of S. santolinifolia and S. eremophila is so high that we may consider them chemically identical. PMID- 22782875 TI - Variation of volatiles in Tunisian populations of Thymbra capitata (L.) Cav. (Lamiaceae). AB - Volatiles from 14 wild Tunisian populations of Thymbra capitata (=Thymus capitatus Hoffmanns. et Link=Coridothymus capitatus Rchb.f.), sampled in five ecological areas (sub-humid, upper semi-arid, mean semi-arid, lower semi-arid, and upper arid areas) were analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) techniques. Thirty-nine constituents representing 94.2 to 99.5% of the total oil were identified. Carvacrol (38; 51.1 75.9%), p-cymene (13; 3.7-15%), gamma-terpinene (12; 1.4-11.9%), and trans-beta caryophyllene (22; 2.9-4.6%) are the major compounds. A significant variation among populations and population's bioclimatic stage for the majority of compounds was shown. The chemical population structure, estimated using a principal-component analysis (PCA) and an unweighted pair group method with arithmetic mean (UPGMA) cluster analysis performed on all populations and compounds and based on Euclidean distances among populations, was high. Both methods allowed separation of the populations into distinct groups defined rather by minor than by major compounds. The spatial compound distribution is linked to ecological factors, indicating that local selective environmental factors influence chemical-composition diversity. Conservation strategies should involve all populations because of their low size and their high level of destruction. Populations exhibiting particular compounds other than the major ones should first be protected. In situ conservation of populations should be accomplished appropriately according to bioclimate. PMID- 22782876 TI - Environment-related variations of the composition of the essential oils of rosemary (Rosmarinus officinalis L.) in the Balkan Penninsula. AB - Composition of the essential oils of Rosmarinus officinalis of ten populations from the Balkan Peninsula were determined by GC/FID and GC/MS. The main constituents were 1,8-cineole, camphor, alpha-pinene, and borneol. Multivariate statistical analysis (UPGMA cluster analysis and principal-component analysis (PCA)) revealed two major types of rosemary oil, i.e., 1,8-cineole and camphor type, and two intermediate types, i.e., camphor/1,8-cineole/borneol type and 1,8 cineole/camphor type. The regression analyses (simple linear regression and stepwise multiple regression) have shown that, with respect to basic geographic, orographic, and 19 bioclimatic characteristics of each population, bioclimatic factor temperature of habitat represented the dominant abiogenetic factor, which, in chemical sense, led to differentiation of populations in the studied region. Also, the regression analysis have shown that some constituents of essential oils are independent of any single bioclimatic factors. However, some constituents display statistically significant correlations with some abiotic factors. PMID- 22782877 TI - Volatile secondary metabolites of Micromeria dalmatica Benth. (Lamiaceae): biosynthetical and chemotaxonomical aspects. AB - Analysis by GC and GC/MS of the essential oil obtained from above-ground parts of Micromeria dalmatica Benth. allowed the identification of 116 components, comprising 93.6% of the total oil composition. The major compounds are 3 oxygenated p-menthane monoterpenes and were identified as pulegone (29.6%), menthone (11.7%), and piperitenone (10.8%). The chemical composition of this and additional 30 oils obtained from selected Micromeria Benth. taxa were compared by using multivariate statistical analysis (agglomerative hierarchical cluster analysis and principal component analysis (PCA)). The results of statistical analyses, as well as the domination of different concurrent p-menthane-skeleton type monoterpene biosynthetical sub-branches in the compared M. dalmatica samples, implied the occurrence of at least two different chemotypes of the mentioned species. PMID- 22782878 TI - Chemotypification of Astrantia major L. (Apiaceae): essential-oil and lignan profiles of fruits. AB - The fruit essential oils of two populations of Astrantia major L. (Apiaceae, subfamily Saniculoideae) were analyzed in detail by GC and GC/MS analyses. Seventy-six constituents identified accounted for 92.7-94.0% of the oils. The two oils differed significantly: the wild-growing population from Serbia contained zingiberene (47.9%), beta-bisabolene (9.7%), and beta-sesquiphellandrene (7.9%), while the one from Poland (botanical gardens) was sesquiterpene-poor with the major contributors oleic acid (38.6%), nonacosane (15.4%), and linoleic acid (5.1%). Motivated by the unresolved taxonomical relations between the Saniculoideae and Apioideae subfamilies, we performed multivariate statistical analyses on the compositional data of these A. major samples, and additional 14 Saniculoideae and 31 Apioideae taxa. This allowed us to assess the chemotaxonomical usefulness of such chemical data in differentiating taxa from these two Apiaceae subfamilies and to corroborate the existence of at least two A. major chemotypes. Diethyl ether extracts of the two samples of A. major fruits yielded seven diaryltetrahydrofurofurano lignans. Except for eudesmin that has been found for the first time in a Saniculoideae taxon, all other lignans (magnolin, epimagnolins A and B, epieudesmin, yangambin, and epiyangambin) are new for the entire plant family Apiaceae. The lignan profiles also supported the existence of two separate A. major chemotypes. PMID- 22782879 TI - Diverse secondary metabolites produced by marine-derived fungus Nigrospora sp. MA75 on various culture media. AB - Bioassay-guided isolation of a fungal strain Nigrospora sp. MA75, an endophytic fungus obtained from the marine semi-mangrove plant Pongamia pinnata, which was fermented on three different culture media, resulted in the isolation and identification of seven known compounds, 2, 3, and 5-9, from a medium containing 3.5% NaCl, while a new compound, 2,3-didehydro-19alpha-hydroxy-14 epicochlioquinone B (10) was obtained from the medium containing 3.5% NaI. In addition, two new griseofulvin derivatives, 6-O-desmethyldechlorogriseofulvin (1) and 6'-hydroxygriseofulvin (4), were isolated and identified from the rice solid medium. Dechlorogriseofulvin (2) and griseofulvin (3) were the major components in fermentation extracts of all these culture media, while compounds 1 and 4, 5 and 6, and 10 were only present in the extract of respective culture medium. The structures of these compounds were elucidated by detailed spectroscopic analysis, and the absolute configuration of 1 was determined by CD measurement. Compounds 9 and 10 exhibited antibacterial activities toward five tested bacterial strains, while compounds 5, 6, and 8 selectively inhibited MRSA, E. coli, and S. epidermidis, and compound 3 showed moderate activity against V. mali and S. solani. Moreover, compound 10 potently inhibited the growth of MCF-7, SW1990, and SMMC7721 tumor cell lines with IC(50) values of 4, 5, and 7 MUg/ml, respectively. PMID- 22782880 TI - Jiangxienone, a new compound with potent cytotoxicity against tumor cells from traditional Chinese medicinal mushroom Cordyceps jiangxiensis. AB - A new compound, named jiangxienone, has been isolated from a culture of the traditional Chinese medicinal mushroom Cordyceps jiangxiensis, and its chemical structure was established on the basis of spectroscopic and chemical techniques. Jiangxienone showed potent cytotoxic effects against human gastric adenocarcinoma SGC-7901 cell and human lung carcinoma A549 cell with IC(50) values ranging from 1.38 to 2.93 MUM, i.e., with at least approximately six-fold stronger cytotoxicity than cisplatin, a first-line chemotherapy drug for cancer patients. PMID- 22782881 TI - Extraction of the essential oil from endemic Origanum bilgeri P.H.Davis with two different methods: comparison of the oil composition and antibacterial activity. AB - The antibacterial activity and chemical composition of the essential oils (EOs) isolated from Origanum bilgeri P.H.Davis by two different extraction methods, i.e., hydrodistillation (HD) and solvent-free microwave extraction (SFME), were examined. This endemic Origanum species had shown very good antibacterial activity. The composition of the O. bilgeri EOs obtained by SFME and HD was investigated by GC/MS analysis. The main components of the oils obtained by both methods were carvacrol (90.20-84.30%), p-cymene (3.40-5.85%), gamma-terpinene (0.47-1.20%), and thymol (0.69-1.08%). The EO isolation by SFME offered many important advantages, including a higher extraction yield, a shorter extraction time, and a higher content of the active component carvacrol. The carvacrol-rich oils obtained by both HD and SFME showed a good antibacterial activity. The largest inhibition zones were observed for the O. bilgeri EO obtained by SFME. Our study suggests that O. bilgeri EO has the potential to be used as preventative against bacterial contamination in many foods, instead of the common synthetic antimicrobial products. PMID- 22782882 TI - Essential-oil diversity of three Calamintha species from Greece. AB - The aim of the present study was to contribute to the knowledge of the essential oil composition of the Calamintha officinalis-nepeta complex in Greece and to clarify the main patterns of its variation. The oils obtained from 22 wild growing populations of C. glandulosa, C. nepeta, and C. menthifolia were studied. They could be classified into two different chemotypes, which correspond to the main biosynthetic routes of the C(3)-oxygenated p-menthane compounds. Chemotype I includes oils rich in trans-piperitone oxide, cis-piperitone oxide, and piperitenone oxide, while Chemotype II comprises oils rich in pulegone and menthone or menthone and isomenthone. Within both chemotypes, quantitative fluctuations of the main components were observed. Comparison with published data showed that the presence of Chemotype II has not been observed before in C. menthifolia, while Chemotype I has been reported in C. nepeta plants from Greece for the first time. PMID- 22782883 TI - Influence of mannosylation on immunostimulating activity of adamant-1-yl tripeptide. AB - The mannosylated derivative of adamant-1-yl tripeptide (D-(Ad-1-yl)Gly-L-Ala-D isoGln) was prepared to study the effects of mannosylation on adjuvant (immunostimulating) activity. Mannosylated adamant-1-yl tripeptide (Man-OCH(2) CH(Me)CO-D-(Ad-1-yl)Gly-L-Ala-D-isoGln) is a non-pyrogenic, H(2) O-soluble, and non-toxic compound. Adjuvant activity of mannosylated adamantyl tripeptide was tested in the mouse model with ovalbumin as an antigen and in comparison to the parent tripeptide and peptidoglycan monomer (PGM, beta-D-GlcNAc-(1->4)-D-MurNAc-L Ala-D-isoGln-mesoDAP(epsilonNH(2) )-D-Ala-D-Ala), a well-known effective adjuvant. The mannosylation of adamantyl tripeptide caused the amplification of its immunostimulating activity in such a way that it was comparable to that of PGM. PMID- 22782884 TI - Isolation and neuroprotective activities of acylated iridoids from Valeriana jatamansi. AB - Three new iridoids, jatairidoids A-C (1-3, resp.), have been isolated from the roots of Valeriana jatamansi (V. wallichii). Their structures were elucidated by spectroscopic methods (IR, ESI-MS, HR-ESI-MS, 1D- and 2D-NMR). Compounds 1 and 2 are C(3)-epimers. The three compounds were evaluated for their neuroprotective effects against MPP(+)-induced neuronal cell death in human dopaminergic neuroblastoma SH-SY5Y cells. All the isolates exhibited moderate neuroprotective effects. PMID- 22782885 TI - Comparative chemical and molecular variability of Cananga odorata (Lam.) Hook.f. & Thomson forma genuina (ylang-ylang) in the Western Indian Ocean Islands: implication for valorization. AB - Cananga odorata (Lam.) Hook.f. & Thomson forma genuina (Annonaceae) is a tropical tree, grown for the production of ylang-ylang essential oil, which is extracted from its fresh and mature flowers. Despite its economic and social importance, very little information is available on its variability and the possible factors causing it. Therefore, the relationship between the genetic structure, revealed by amplified fragment length polymorphism (AFLP), and the essential oil chemical composition, determined by GC/MS analysis, of ylang-ylang grown in semi-managed systems in three Indian Ocean islands (Grande Comore, Mayotte, and Madagascar) was investigated. Our results revealed a low genetic variation within plantations and contrasted situations between islands. Variations of the chemical composition could be observed within plantations and between islands. The genetic differentiation pattern did not match the observed pattern of chemical variability. Hence, the chemical variation could not be attributed to a genetic control. As Grande Comore, Madagascar, and Mayotte present different environmental and agronomic conditions, it can be concluded that the influence of these conditions on the ylang-ylang essential oil composition is consistent with the patterns observed. Finally, several strategies were proposed to valorize the chemical composition variations. PMID- 22782886 TI - ZO-1 regulates Erk, Smad1/5/8, Smad2, and RhoA activities to modulate self renewal and differentiation of mouse embryonic stem cells. AB - ZO-1/Tjp1 is a cytosolic adaptor that links tight junction (TJ) transmembrane proteins to the actin cytoskeleton and has also been implicated in regulating cell proliferation and differentiation by interacting with transcriptional regulators and signaling proteins. To explore possible roles for ZO-1 in mouse embryonic stem cells (mESCs), we inactivated the ZO-1 locus by homologous recombination. The lack of ZO-1 was found to affect mESC self-renewal and differentiation in the presence of leukemia-inhibiting factor (LIF) and Bmp4 or following removal of the growth factors. Our data suggest that ZO-1 suppresses Stat3 and Smad1/5/8 activities and sustains extracellular-signal-regulated kinase (Erk) activity to promote mESC differentiation. Interestingly, Smad2, critical for human but not mESC self-renewal, was hyperactivated in ZO-1(-/-) mESCs and RhoA protein levels were concomitantly enhanced, suggesting attenuation of the noncanonical transforming growth factor beta (Tgfbeta)/Activin/Nodal pathway that mediates ubiquitination and degradation of RhoA via the TJ proteins Occludin, Par6, and Smurf1 and activation of the canonical Smad2-dependent pathway. Furthermore, Bmp4-induced differentiation of mESCs in the absence of LIF was suppressed in ZO-1(-/-) mESCs, but differentiation down the neural or cardiac lineages was not disturbed. These findings reveal novel roles for ZO-1 in mESC self-renewal, pluripotency, and differentiation by influencing several signaling networks that regulate these processes. Possible implications for the differing relevance of Smad2 in mESC and human ESC self-renewal and how ZO-1 may connect to the different pathways are discussed. PMID- 22782887 TI - Carbon-carbon bond formation: palladium-catalyzed oxidative cross-coupling of N tosylhydrazones with allylic alcohols. AB - In the zone: Pd-catalyzed oxidative cross-coupling of N-tosylhydrazones with allylic alcohols leads to C?C bond formation. A palladium-carbene migratory insertion is proposed to play the key role in this transformation. The reaction proceeds with readily available starting materials to afford substituted alkenes in a highly stereoselective manner. PMID- 22782888 TI - Investigations on the photoregulation of chloroplast movement and leaf positioning in Arabidopsis. AB - We recently investigated the roles of the phototropin 1 (PHOT1) LOV (light, oxygen or voltage) domains in mediating phototropic curvature in transgenic Arabidopsis seedlings expressing either wild-type PHOT1 or PHOT1 with one or both LOV domains inactivated by a single amino acid replacement. We have now investigated the role of the PHOT1 LOV domains in chloroplast movement and in leaf positioning in response to blue light. Low fluence rate blue light is known to mediate a chloroplast accumulation response and high fluence rate blue light an avoidance response in Arabidopsis leaves. As was the case for phototropism, LOV2 of PHOT1 is essential for chloroplast accumulation and LOV1 is dispensable. PHOT1 LOV2 is also essential to maintain developing primary leaves in a horizontal position under white light from above and LOV1 is again dispensable. A red light pulse given to dark-adapted light-grown plants followed by 2 h of darkness enhances both the chloroplast accumulation response under dim blue light and the chloroplast avoidance response under strong blue light. The effect is far red reversible. This photoreversible response is normal in a phyB null mutant but does not appear in a phyA null mutant. These results suggest that phyA mediates the enhancement, induced by a red light pulse, of blue light-induced chloroplast movements. PMID- 22782889 TI - Nanosheet-enhanced enantioselectivity in the vanadium-catalyzed asymmetric epoxidation of allylic alcohols. AB - The use of suitable chiral ligands is an efficient means of producing highly enantioselective transition-metal catalysts. Herein, we report a facile, economic, and effective strategy for the design of chiral ligands that demonstrate enhanced enantioselectivity and catalytic efficacy. Our simple strategy employs naturally occurring or synthetic inorganic nanosheets as huge and rigid planar substituents for, but not limited to, naturally available alpha amino-acid ligands; these ligands were successfully used in the vanadium catalyzed asymmetric epoxidation of allylic alcohols. The crucial role of the inorganic nanosheets as planar substituents in improving the enantioselectivity of the reaction was clearly revealed by relating the observed enantiomeric excess with the distribution of the catalytic centers and the accessibility of the substrate molecules to the catalytic sites. DFT calculations indicated that the LDH layer improved the enantioselectivity by influencing the formation and stability of the catalytic transition states, both in terms of steric resistance and H-bonding interactions. PMID- 22782890 TI - Detoxication of benzo[a]pyrene-7,8-dione by sulfotransferases (SULTs) in human lung cells. AB - Polycyclic aromatic hydrocarbons (PAH) are environmental and tobacco carcinogens. Human aldo-keto reductases catalyze the metabolic activation of proximate carcinogenic PAH trans-dihydrodiols to yield electrophilic and redox-active o quinones. Benzo[a]pyrene-7,8-dione a representative PAH o-quinone is reduced back to the corresponding catechol to generate a futile redox-cycle. We investigated whether sulfonation of PAH catechols by human sulfotransferases (SULT) could intercept the catechol in human lung cells. RT-PCR identified SULT1A1, -1A3, and 1E1 as the isozymes expressed in four human lung cell lines. The corresponding recombinant SULTs were examined for their substrate specificity. Benzo[a]pyrene 7,8-dione was reduced to benzo[a]pyrene-7,8-catechol by dithiothreitol under anaerobic conditions and then further sulfonated by the SULTs in the presence of 3'-[(35)S]phosphoadenosine 5'-phosphosulfate as the sulfonate group donor. The human SULTs catalyzed the sulfonation of benzo[a]pyrene-7,8-catechol and generated two isomeric benzo[a]pyrene-7,8-catechol O-monosulfate products that were identified by reversed phase HPLC and by LC-MS/MS. The various SULT isoforms produced the two isomers in different proportions. Two-dimensional (1)H and (13)C NMR assigned the two regioisomers of benzo[a]pyrene-7,8-catechol monosulfate as 8 hydroxy-benzo[a]pyrene-7-O-sulfate (M1) and 7-hydroxy-benzo[a]pyrene-8-O-sulfate (M2), respectively. The kinetic profiles of three SULTs were different. SULT1A1 gave the highest catalytic efficiency (k(cat)/K(m)) and yielded a single isomeric product corresponding to M1. By contrast, SULT1E1 showed distinct substrate inhibition and formed both M1 and M2. Based on expression levels, catalytic efficiency, and the fact that the lung cells only produce M1, it is concluded that the major isoform that can intercept benzo[a]pyrene-7,8-catechol is SULT1A1. PMID- 22782892 TI - STK25 protein mediates TrkA and CCM2 protein-dependent death in pediatric tumor cells of neural origin. AB - The TrkA receptor tyrosine kinase induces death in medulloblastoma cells via an interaction with the cerebral cavernous malformation 2 (CCM2) protein. We used affinity proteomics to identify the germinal center kinase class III (GCKIII) kinases STK24 and STK25 as novel CCM2 interactors. Down-modulation of STK25, but not STK24, rescued medulloblastoma cells from NGF-induced TrkA-dependent cell death, suggesting that STK25 is part of the death-signaling pathway initiated by TrkA and CCM2. CCM2 can be phosphorylated by STK25, and the kinase activity of STK25 is required for death signaling. Finally, STK25 expression in tumors is correlated with positive prognosis in neuroblastoma patients. These findings delineate a death-signaling pathway downstream of neurotrophic receptor tyrosine kinases that may provide targets for therapeutic intervention in pediatric tumors of neural origin. PMID- 22782891 TI - Targeting serous epithelial ovarian cancer with designer zinc finger transcription factors. AB - Ovarian cancer is the leading cause of death among gynecological malignancies. It is detected at late stages when the disease is spread through the abdominal cavity in a condition known as peritoneal carcinomatosis. Thus, there is an urgent need to develop novel therapeutic interventions to target advanced stages of ovarian cancer. Mammary serine protease inhibitor (Maspin) represents an important metastasis suppressor initially identified in breast cancer. Herein we have generated a sequence-specific zinc finger artificial transcription factor (ATF) to up-regulate the Maspin promoter in aggressive ovarian cancer cell lines and to interrogate the therapeutic potential of Maspin in ovarian cancer. We found that although Maspin was expressed in some primary ovarian tumors, the promoter was epigenetically silenced in cell lines derived from ascites. Transduction of the ATF in MOVCAR 5009 cells derived from ascitic cultures of a TgMISIIR-TAg mouse model of ovarian cancer resulted in tumor cell growth inhibition, impaired cell invasion, and severe disruption of actin cytoskeleton. Systemic delivery of lipid-protamine-RNA nanoparticles encapsulating a chemically modified ATF mRNA resulted in inhibition of ovarian cancer cell growth in nude mice accompanied with Maspin re-expression in the treated tumors. Gene expression microarrays of ATF-transduced cells revealed an exceptional specificity for the Maspin promoter. These analyses identified novel targets co-regulated with Maspin in human short-term cultures derived from ascites, such as TSPAN12, that could mediate the anti-metastatic phenotype of the ATF. Our work outlined the first targeted, non-viral delivery of ATFs into tumors with potential clinical applications for metastatic ovarian cancers. PMID- 22782893 TI - Specialized Hsp70 chaperone (HscA) binds preferentially to the disordered form, whereas J-protein (HscB) binds preferentially to the structured form of the iron sulfur cluster scaffold protein (IscU). AB - The Escherichia coli protein IscU serves as the scaffold for Fe-S cluster assembly and the vehicle for Fe-S cluster transfer to acceptor proteins, such as apoferredoxin. IscU populates two conformational states in solution, a structured conformation (S) that resembles the conformation of the holoprotein IscU-[2Fe-2S] and a dynamically disordered conformation (D) that does not bind metal ions. NMR spectroscopic results presented here show that the specialized Hsp70 chaperone (HscA), alone or as the HscA-ADP complex, preferentially binds to and stabilizes the D-state of IscU. IscU is released when HscA binds ATP. By contrast, the J protein HscB binds preferentially to the S-state of IscU. Consistent with these findings, we propose a mechanism in which cluster transfer is coupled to hydrolysis of ATP bound to HscA, conversion of IscU to the D-state, and release of HscB. PMID- 22782894 TI - Amyloid precursor protein regulates netrin-1-mediated commissural axon outgrowth. AB - The multifunctional protein netrin-1 was initially discovered as the main attractive cue for commissural axon guidance by acting through its receptor DCC. Recently, we have shown that netrin-1 also interacts with the orphan transmembrane receptor amyloid precursor protein (APP). APP is cleaved by proteases, generating amyloid-beta peptide, the main component of the amyloid plaques that are associated with Alzheimer disease. Our previous work demonstrated that via its interaction with APP, netrin-1 is a negative regulator of amyloid-beta production in adult brain, but the biological relevance of APP/netrin-1 interaction under non-pathological conditions was unknown. We show here that during commissural axon navigation, APP, expressed at the growth cone, is part of the DCC receptor complex mediating netrin-1-dependent axon guidance. APP interacts with DCC in the presence of netrin-1 and enhances netrin-1-mediated DCC intracellular signaling, such as MAPK activation. Inactivation of APP in mice is associated with reduced commissural axon outgrowth. Thus, APP functionally acts as a co-receptor for DCC to mediate axon guidance. PMID- 22782895 TI - Deciphering the role of CD1e protein in mycobacterial phosphatidyl-myo-inositol mannosides (PIM) processing for presentation by CD1b to T lymphocytes. AB - Lipids are important antigens that induce T cell-mediated specific immune responses. They are presented to T lymphocytes by a specific class of MHC-I like proteins, termed CD1. The majority of the described CD1-presented mycobacterial antigens are presented by the CD1b isoform. We previously demonstrated that the stimulation of CD1b-restricted T cells by the hexamannosylated phosphatidyl-myo inositol (PIM(6)), a family of mycobacterial antigens, requires a prior partial digestion of the antigen oligomannoside moiety by alpha-mannosidase and that CD1e is an accessory protein absolutely required for the generation of the lipid immunogenic form. Here, we show that CD1e behaves as a lipid transfer protein influencing lipid immunoediting and membrane transfer of PIM lipids. CD1e selectively assists the alpha-mannosidase-dependent digestion of PIM(6) species according to their degree of acylation. Moreover, CD1e transfers only diacylated PIM from donor to acceptor liposomes and also from membranes to CD1b. This study provides new insight into the molecular mechanisms by which CD1e contributes to lipid immunoediting and CD1-restricted presentation to T cells. PMID- 22782896 TI - A retroelement modifies pre-mRNA splicing: the murine Glrb(spa) allele is a splicing signal polymorphism amplified by long interspersed nuclear element insertion. AB - The glycine receptor-deficient mutant mouse spastic carries a full-length long interspersed nuclear element (LINE1) retrotransposon in intron 6 of the glycine receptor beta subunit gene, Glrb(spa). The mutation arose in the C57BL/6J strain and is associated with skipping of exon 6 or a combination of the exons 5 and 6, thus resulting in a translational frameshift within the coding regions of the GlyR beta subunit. The effect of the Glrb(spa) LINE1 insertion on pre-mRNA splicing was studied using a minigene approach. Sequence comparison as well as motif prediction and mutational analysis revealed that in addition to the LINE1 insertion the inactivation of an exonic splicing enhancer (ESE) within exon 6 is required for skipping of exon 6. Reconstitution of the ESE by substitution of a single residue was sufficient to prevent exon skipping. In addition to the ESE, two regions within the 5' and 3' UTR of the LINE1 were shown to be critical determinants for exon skipping, indicating that LINE1 acts as efficient modifier of subtle endogenous splicing phenotypes. Thus, the spastic allele of the murine glycine receptor beta subunit gene is a two-hit mutation, where the hypomorphic alteration in an ESE is amplified by the insertion of a LINE1 element in the adjacent intron. Conversely, the LINE1 effect on splicing may be modulated by individual polymorphisms, depending on the insertional environment within the host genome. PMID- 22782897 TI - The chemokine CCL5 regulates glucose uptake and AMP kinase signaling in activated T cells to facilitate chemotaxis. AB - Recruitment of effector T cells to sites of infection or inflammation is essential for an effective adaptive immune response. The chemokine CCL5 (RANTES) activates its cognate receptor, CCR5, to initiate cellular functions, including chemotaxis. In earlier studies, we reported that CCL5-induced CCR5 signaling activates the mTOR/4E-BP1 pathway to directly modulate mRNA translation. Specifically, CCL5-mediated mTOR activation contributes to T cell chemotaxis by initiating the synthesis of chemotaxis-related proteins. Up-regulation of chemotaxis-related proteins may prime T cells for efficient migration. It is now clear that mTOR is also a central regulator of nutrient sensing and glycolysis. Herein we describe a role for CCL5-mediated glucose uptake and ATP accumulation to meet the energy demands of chemotaxis in activated T cells. We provide evidence that CCL5 is able to induce glucose uptake in an mTOR-dependent manner. CCL5 treatment of ex vivo activated human CD3(+) T cells also induced the activation of the nutrient-sensing kinase AMPK and downstream substrates ACC-1, PFKFB-2, and GSK-3beta. Using 2-deoxy-d-glucose, an inhibitor of glucose uptake, and compound C, an inhibitor of AMPK, experimental data are presented that demonstrate that CCL5-mediated T cell chemotaxis is dependent on glucose, as these inhibitors inhibit CCL5-mediated chemotaxis in a dose-dependent manner. Altogether, these findings suggest that both glycolysis and AMPK signaling are required for efficient T cell migration in response to CCL5. These studies extend the role of CCL5 mediated CCR5 signaling beyond lymphocyte chemotaxis and demonstrate a role for chemokines in promoting glucose uptake and ATP production to match energy demands of migration. PMID- 22782898 TI - Receptor activator of nuclear factor kappaB ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomy-induced bone loss. AB - Production of the cytokine receptor activator of NFkappaB ligand (RANKL) by lymphocytes has been proposed as a mechanism by which sex steroid deficiency causes bone loss. However, there have been no studies that functionally link RANKL expression in lymphocytes with bone loss in this condition. Herein, we examined whether RANKL expression in either B or T lymphocytes contributes to ovariectomy-induced bone loss in mice. Mice harboring a conditional RANKL allele were crossed with CD19-Cre or Lck-Cre mice to delete RANKL in B or T lymphocytes, respectively. Deletion of RANKL from either cell type had no impact on bone mass in estrogen-replete mice up to 7 months of age. However, mice lacking RANKL in B lymphocytes were partially protected from the bone loss caused by ovariectomy. This protection occurred in cancellous, but not cortical, bone and was associated with a failure to increase osteoclast numbers in the conditional knock-out mice. Deletion of RANKL from T lymphocytes had no impact on ovariectomy-induced bone loss. These results demonstrate that lymphocyte RANKL is not involved in basal bone remodeling, but B cell RANKL does contribute to the increase in osteoclasts and cancellous bone loss that occurs after loss of estrogen. PMID- 22782899 TI - Comparison of spheroids formed by rat glioma stem cells and neural stem cells reveals differences in glucose metabolism and promising therapeutic applications. AB - Cancer stem cells (CSCs) are thought to be partially responsible for cancer resistance to current therapies and tumor recurrence. Dichloroacetate (DCA), a compound capable of shifting metabolism from glycolysis to glucose oxidation, via an inhibition of pyruvate dehydrogenase kinase was used. We show that DCA is able to shift the pyruvate metabolism in rat glioma CSCs but has no effect in rat neural stem cells. DCA forces CSCs into oxidative phosphorylation but does not trigger the production of reactive oxygen species and consecutive anti-cancer apoptosis. However, DCA, associated with etoposide or irradiation, induced a Bax dependent apoptosis in CSCs in vitro and decreased their proliferation in vivo. The former phenomenon is related to DCA-induced Foxo3 and p53 expression, resulting in the overexpression of BH3-only proteins (Bad, Noxa, and Puma), which in turn facilitates Bax-dependent apoptosis. Our results demonstrate that a small drug available for clinical studies potentiates the induction of apoptosis in glioma CSCs. PMID- 22782900 TI - Cathepsin B is secreted apically from Xenopus 2F3 cells and cleaves the epithelial sodium channel (ENaC) to increase its activity. AB - The epithelial sodium channel (ENaC) plays an important role in regulating sodium balance, extracellular volume, and blood pressure. Evidence suggests the alpha and gamma subunits of ENaC are cleaved during assembly before they are inserted into the apical membranes of epithelial cells, and maximal activity of ENaC depends on cleavage of the extracellular loops of alpha and gamma subunits. Here, we report that Xenopus 2F3 cells apically express the cysteine protease cathepsin B, as indicated by two-dimensional gel electrophoresis and mass spectrometry analysis. Recombinant GST ENaC alpha, beta, and gamma subunit fusion proteins were expressed in Escherichia coli and then purified and recovered from bacterial inclusion bodies. In vitro cleavage studies revealed the full-length ENaC alpha subunit fusion protein was cleaved by active cathepsin B but not the full-length beta or gamma subunit fusion proteins. Both single channel patch clamp studies and short circuit current experiments show ENaC activity decreases with the application of a cathepsin B inhibitor directly onto the apical side of 2F3 cells. We suggest a role for the proteolytic cleavage of ENaC by cathepsin B, and we suggest two possible mechanisms by which cathepsin B could regulate ENaC. Cathepsin B may cleave ENaC extracellularly after being secreted or intracellularly, while ENaC is present in the Golgi or in recycling endosomes. PMID- 22782901 TI - A novel allosteric inhibitor of macrophage migration inhibitory factor (MIF). AB - Macrophage migration inhibitory factor (MIF) is a catalytic cytokine and an upstream mediator of the inflammatory pathway. MIF has broad regulatory properties, dysregulation of which has been implicated in the pathology of multiple immunological diseases. Inhibition of MIF activity with small molecules has proven beneficial in a number of disease models. Known small molecule MIF inhibitors typically bind in the tautomerase site of the MIF trimer, often covalently modifying the catalytic proline. Allosteric MIF inhibitors, particularly those that associate with the protein by noncovalent interactions, could reveal novel ways to block MIF activity for therapeutic benefit and serve as chemical probes to elucidate the structural basis for the diverse regulatory properties of MIF. In this study, we report the identification and functional characterization of a novel allosteric MIF inhibitor. Identified from a high throughput screening effort, this sulfonated azo compound termed p425 strongly inhibited the ability of MIF to tautomerize 4-hydroxyphenyl pyruvate. Furthermore, p425 blocked the interaction of MIF with its receptor, CD74, and interfered with the pro-inflammatory activities of the cytokine. Structural studies revealed a unique mode of binding for p425, with a single molecule of the inhibitor occupying the interface of two MIF trimers. The inhibitor binds MIF mainly on the protein surface through hydrophobic interactions that are stabilized by hydrogen bonding with four highly specific residues from three different monomers. The mode of p425 binding reveals a unique way to block the activity of the cytokine for potential therapeutic benefit in MIF-associated diseases. PMID- 22782902 TI - The protein factor-arrest 11 (Far11) is essential for the toxicity of human caspase-10 in yeast and participates in the regulation of autophagy and the DNA damage signaling. AB - The heterologous expression of human caspase-10 in Saccharomyces cerevisiae induces a lethal phenotype, which includes some hallmarks of apoptosis and autophagy, alterations in the intra-S checkpoint, and cell death. To determine the cellular processes and pathways that are responsible of the caspase-10 induced cell death we have designed a loss-of-function screening system to identify genes that are essential for the lethal phenotype. We observed that the ER-Golgi-localized family of proteins Far, MAPK signaling, the autophagy machinery, and several kinases and phosphatases are essential for caspase-10 toxicity. We also found that the expression of caspase-10 elicits a simultaneous activation of the MAP kinases Fus3, Kss1, and Slt2. Furthermore, the protein Far11, which is a target of MAP kinases, is essential for the dephosphorylation of Atg13 and, consequently, for the induction of autophagy. In addition, Far11 participates in the regulation of the DNA damage response through the dephosphorylation of Rad53. Finally, we have also demonstrated that Far11 is able to physically interact with the phosphatases Pph21, Pph22, and Pph3. Overall, our results indicate that the expression of human caspase-10 in S. cerevisiae activates an intracellular death signal that depends on the Far protein complex and that Far11 may function as a regulator subunit of phosphatases in different processes, thus representing a mechanistic link between them. PMID- 22782903 TI - MicroRNA-125b down-regulates matrix metallopeptidase 13 and inhibits cutaneous squamous cell carcinoma cell proliferation, migration, and invasion. AB - Cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer. Although dysregulation of microRNAs (miRNAs) is known to be involved in a variety of cancers, the role of miRNAs in cSCC is unclear. In this study, we aimed to identify tumor suppressive and oncogenic miRNAs involved in the pathogenesis of cSCC. MiRNA expression profiles in healthy skins (n = 4) and cSCCs (n = 4) were analyzed using MicroRNA Low Density Array. MiR-125b expression was analyzed by quantitative real-time PCR and in situ hybridization in skin biopsies from 40 healthy donors, 13 actinic keratosis, and 74 cSCC patients. The effect of miR 125b was analyzed in wound closure, colony formation, migration, and invasion assays in two cSCC cell lines, UT-SCC-7 and A431. The genes regulated by miR-125b in cSCC were identified by microarray analysis and its direct target was validated by luciferase reporter assay. Comparing cSCC with healthy skin, we identified four up-regulated miRNAs (miR-31, miR-135b, miR-21, and miR-223) and 54 down-regulated miRNAs, including miR-125b, whose function was further examined. We found that miR-125b suppressed proliferation, colony formation, migratory, and invasive capacity of cSCC cells. Matrix metallopeptidase 13 (MMP13) was identified as a direct target suppressed by miR-125b, and there was an inverse relationship between the expression of miR-125b and MMP13 in cSCC. Knockdown of MMP13 expression phenocopied the effects of miR-125b overexpression. These findings provide a novel molecular mechanism by which MMP13 is up-regulated in cSCCs and indicate that miR-125b plays a tumor suppressive role in cSCC. PMID- 22782905 TI - US geriatric mental health workforce needs to expand, says Institute of Medicine. PMID- 22782904 TI - Adenine binding mode is a key factor in triggering the early release of NADH in coenzyme A-dependent methylmalonate semialdehyde dehydrogenase. AB - Structural dynamics associated with cofactor binding have been shown to play key roles in the catalytic mechanism of hydrolytic NAD(P)-dependent aldehyde dehydrogenases (ALDH). By contrast, no information is available for their CoA dependent counterparts. We present here the first crystal structure of a CoA dependent ALDH. The structure of the methylmalonate semialdehyde dehydrogenase (MSDH) from Bacillus subtilis in binary complex with NAD(+) shows that, in contrast to what is observed for hydrolytic ALDHs, the nicotinamide ring is well defined in the electron density due to direct and H(2)O-mediated hydrogen bonds with the carboxamide. The structure also reveals that a conformational isomerization of the NMNH is possible in MSDH, as shown for hydrolytic ALDHs. Finally, the adenine ring is substantially more solvent-exposed, a result that could be explained by the presence of a Val residue at position 229 in helix alpha(F) that reduces the depth of the binding pocket and the absence of Gly-225 at the N-terminal end of helix alpha(F). Substitution of glycine for Val-229 and/or insertion of a glycine residue at position 225 resulted in a significant decrease of the rate constant associated with the dissociation of NADH from the NADH/thioacylenzyme complex, thus demonstrating that the weaker stabilization of the adenine ring is a key factor in triggering the early NADH release in the MSDH catalyzed reaction. This study provides for the first time structural insights into the mechanism whereby the cofactor binding mode is responsible at least in part for the different kinetic behaviors of the hydrolytic and CoA-dependent ALDHs. PMID- 22782906 TI - Government should investigate trusts that charge NHS patients for treatment, says Labour. PMID- 22782907 TI - Every doctor has a duty to report suspected child abuse or neglect, says GMC. PMID- 22782908 TI - Animal experiments rose in 2011 despite coalition pledge to reduce them. PMID- 22782909 TI - GAG layer replenishment therapy for chronic forms of cystitis with intravesical glycosaminoglycans--a review. AB - AIMS: Glycosaminoglycan (GAG) layer replenishment is a cornerstone in the therapy of interstitial cystitis (IC). During the last years intravesical GAG layer replenishment has proven to be an effective treatment for overactive bladder (OAB), radiation cystitis, and recurrent urinary tract infections (UTIs). METHODS: Examination of different substances available for intravesical GAG replenishment and evaluation of the evidence for the treatment of the above mentioned conditions. RESULTS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) database for studies on intravesical GAG replenishment. A total of 27 clinical studies remain relevant to this topic, many of them with mixed patient selection and suboptimal definition of symptom improvement/success. Two placebo controlled studies with hyaluronic acid failed to show superiority and have not been published. One active controlled randomized study has been published showing that chondroitin sulphate 0.2% has a clear benefit for OAB patients. Another study with chondroitin sulphate 2.0% failed to show statistically significant evidence, but was underpowered. CONCLUSIONS: A short number of randomized controlled studies confirm efficacy of intravesical GAG layer replenishment therapy. Concluded from the study background (which comprises also uncontrolled studies), so far chondroitin sulphate 0.2% is in favor for intravesical GAG layer replenishment therapy. In general, large-scale trials are urgently needed to underline the benefit of this type of therapy. PMID- 22782910 TI - Interleukin-6 promoter variants, prostate cancer risk, and survival. AB - BACKGROUND: Inflammation has been implicated in prostate cancer (PCa) pathogenesis. Promoter DNA variants responsible for differential expression of key cytokines may therefore influence susceptibility to PCa. METHODS: Two interleukin-6 (IL-6) promoter variants, -174G>C and -6331T>C, were genotyped for association with PCa risk and survival using the Risk Factors for Prostate Cancer Study (RFPCS, 825 cases and 732 controls) and the Melbourne Collaborative Cohort Study (MCCS, 818 cases and 1,745 controls). Impact of genotypes on IL-6 transcriptional activity was measured using Low Density Arrays. RESULTS: A significant increase in IL-6 transcriptional activity in malignant compared to benign prostate tissue supports a role for IL-6 in PCa. The -174G>C variant showed no association with PCa risk, overall survival, or IL-6 transcriptional activity. The -6331 C-allele was significantly associated with an increased risk in the RFPCS (OR = 1.29, 95% CI = 1.08-1.54), but not in the MCCS. In the MCCS however, cases presenting with a CC genotype conferred a higher risk of mortality (HR = 2.27, 95% CI = 1.34-3.85), which was maintained although reduced overall in the pooled analysis with RFPCS (HR = 1.68, 95% CI = 1.10-2.54). Furthermore, we associate the minor C-allele with a significant decrease in IL-6 transcriptional activity. CONCLUSIONS: While our study refutes a role for IL-6 -174G>C, it is the first to implicate -6331T>C with PCa risk and poor survival. Our observation that -6331T>C has a significant impact on IL-6 transcriptional activity, calls for further investigations into the role of this variant as a novel PCa biomarker. PMID- 22782911 TI - Transplantation of side population cells restores the function of damaged exocrine glands through clusterin. AB - Stem cell-based therapy has been proposed as a promising strategy for regenerating tissues lost through incurable diseases. Side population (SP) cells have been identified as putative stem cells in various organs. To examine therapeutic potential of SP cells in hypofunction of exocrine glands, SP cells isolated from mouse exocrine glands, namely, lacrimal and salivary glands, were transplanted into mice with irradiation-induced hypofunction of the respective glands. The secretions from both glands in the recipient mice were restored within 2 months of transplantation, although the transplanted cells were only sparsely distributed and produced no outgrowths. Consistent with this, most SP cells were shown to be CD31-positive endothelial-like cells. In addition, we clarified that endothelial cell-derived clusterin, a secretory protein, was an essential factor for SP cell-mediated recovery of the hypofunctioning glands because SP cells isolated from salivary glands of clusterin-deficient mice had no therapeutic potential, whereas lentiviral transduction of clusterin restored the hypofunction. In vitro and in vivo studies showed that clusterin had an ability to directly inhibit oxidative stress and oxidative stress-induced cell damage. Thus, endothelial cell-derived clusterin possibly inhibit oxidative stress induced hypofunction of these glands. PMID- 22782912 TI - HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice. AB - SCOPE: The effects of hydroxypropyl methylcellulose (HPMC), a highly viscous nonfermentable soluble dietary fiber, were evaluated on adipose tissue inflammation and insulin resistance in diet-induced obese (DIO) mice fed a high fat (HF) diet supplemented with either HPMC or insoluble fiber. METHODS AND RESULTS: DIO C57BL/6J mice were fed a HF diet supplemented with 6% HPMC or 6% microcrystalline cellulose (MCC). Gene expression analyses of epididymal adipose tissue by exon microarray and real-time PCR along with glucose and insulin tolerance and intestinal permeability were assessed. HPMC-fed mice exhibited significantly reduced body weight gain and adipose tissue weight as well as reduced areas under the curve for 2-h insulin and glucose responses. HPMC significantly decreased HF diet-induced intestinal permeability. Overall, HPMC enhanced insulin sensitivity and glucose metabolism and downregulated genes related to inflammation and immune response, adipogenesis, and oxidative stress markers. Pathway analysis of microarray data identified lipid metabolism, inflammatory disease, and acute phase response pathways as being differentially regulated by HPMC. CONCLUSION: These results suggest HPMC consumption ameliorates HF diet effects on obesity-induced insulin resistance, adipose tissue inflammatory and immune responses, weight gain, as well as intestinal permeability. PMID- 22782913 TI - The structural diversity triggered by intermolecular interactions between Au(I)S2 groups: aurophilia and beyond. AB - The present study is aimed at elucidating the factors that direct the assembly of a specific family of Au(I) species. The assembly of Au(I) centers and dithiocarboxylato or xanthato ligands results in a surprising structural diversity observed by single-crystal X-ray diffraction. However, in solution, just evidences for discrete bimetallic [Au(2)L(2)] species have been observed. Interestingly, when dithiocarboxylato ligands have been used, a reversible supramolecular assembly has been observed forming the supramolecules of formulae [Au(2)L(2)](2) and [Au(2)L(2)](3). Initial studies on luminescent properties have been carried out at variable temperature. All the compounds show red emissions in the solid state at very similar energies, suggesting that the intramolecular interactions play a more relevant role in the luminescent properties than the intermolecular ones. The computational studies indicate that not only Au...Au interactions, but also Au...S and S...S ones play a role in the structure and energetic of the supramolecular species, as well as for the choice between supramolecular association or intramolecular oligomerization. PMID- 22782914 TI - The 39 steps: evading error and deciphering the secrets for accurate dynamic susceptibility contrast MRI. AB - Dynamic susceptibility contrast (DSC) MRI is the most commonly used MRI method to assess cerebral perfusion and other related haemodynamic parameters. Although the technique is well established and used routinely in clinical centres, there are still many problems that impede accurate perfusion quantification. In this review article, we present 39 steps which guide the reader through the theoretical principles, practical decisions, potential problems, current limitations and latest advances in DSC-MRI. The 39 steps span the collection, analysis and interpretation of DSC-MRI data, expounding issues and possibilities relating to the contrast agent, the acquisition of DSC-MRI data, data pre-processing, the contrast concentration-time course, the arterial input function, deconvolution, common perfusion parameters, post-processing possibilities, patient studies, absolute versus relative quantification and automated analysis methods. PMID- 22782915 TI - Measuring the outcome of structured spousal violence risk assessments using the B SAFER: risk in relation to recidivism and intervention. AB - In this study, 216 risk assessments conducted by law enforcement officers in a suburb of Stockholm using the Brief Spousal Assault Form for the Evaluation of Risk (B-SAFER) were followed up and correlated to both recidivism and type of protective actions implemented by the police. The results showed high recidivism rates across all risk categories, except in the highest risk group, where the recidivism rate was significantly lower. This finding suggests a poor, and even negative, predictive power of the police risk assessments: the higher the police assessed risk, the lower the recidivism rate. However, it was clear that the police did very little, or nothing, in cases not assessed as high risk. All resources appear to have been directed to the high-risk cases, which seems to have had a preventive effect. Our results point to the importance of studying the nature and extent of protective actions taken in response to risk assessment, before drawing conclusions about the predictive validity of risk assessment instruments. PMID- 22782916 TI - Relationship between prostate cancer gene 3 (PCA3) and characteristics of tumor aggressiveness. AB - BACKGROUND: Data supporting prostate cancer gene 3 (PCA3) as prognostic marker are still inconsistent. With special emphasis to Gleason pattern specific tumor volumes (TVs) the relationships between PCA3 score and different characteristics of tumor aggressiveness were meticulously analyzed. METHODS: In 127 patients treated with radical prostatectomy for clinically localized prostate cancer, urinary PCA3 score was quantified using ProgensaTM PCA3 assay. Total TV and Gleason patterns' specific tumor volumes (GPTV) were assessed by computer assisted planimetry. Spearman's rank correlations coefficients (r) were calculated to assess relationships between PCA3 and TV as well as GPTV. Regression analyses were performed to estimate the relationship between PCA3 and TV as well as non-organ confined disease. RESULTS: Mean patients' age was 60.8 years. Patients showed a mean PSA level of 8.1 ng/ml and a mean PCA3 score of 68.5. PCA3 was not significantly correlated with TV (r = 0.131, P = 0.142). Stratified by Gleason score groups <= 6, 7, and >= 8, PCA3 showed no significant correlations with TV. In a subgroup analysis of 50 patients with different primary and secondary Gleason patterns there was neither a correlation with the primary GPTV (r = 0.071, P = 0.626) nor with the secondary GPTV (r = 0.052, P = 0.722). The PCA3 score was neither an independent predictor for TV nor for non organ confined disease. CONCLUSIONS: The PCA3 score did not show any significant correlation with TV, primary or secondary GPTV. Moreover, the PCA3 score was not an independent predictor for TV or for non-organ confined disease. Thus, the PCA3 score had no impact for the prediction of aggressive prostate cancers. PMID- 22782917 TI - Screening for postmenopausal osteoporosis with any modality is cost-effective including screening initiation at 55 years of age. PMID- 22782918 TI - The association between proton pump inhibitor use and hip fracture cannot be explained by differences in dietary and lifestyle choices. PMID- 22782919 TI - Closure of a patent foramen ovale with a device does not offer a greater benefit than medical therapy alone for the prevention of recurrent cerebrovascular events. PMID- 22782920 TI - Transition to osteoporosis for 10% of women takes 17 years for those with normal bone density, 5 years for those with moderate osteopenia: implications for the frequency of bone density testing. PMID- 22782921 TI - The role of angiotensin receptor blockers in the prevention of cardiovascular and renal disease: time for reassessment? AB - Angiotensin receptor blockers (ARB) have been recommended as a first option for the management of hypertension by guidelines, particularly in patients at high cardiovascular risk. The preference for ARB in these conditions is based on their neutral metabolic effects, and on direct cardiac and renal protective effects independent of the blood pressure-lowering effect (pleiotropic effects). Nonetheless, six large clinical trials designed to demonstrate such effects in patients at high cardiovascular risk, comparing ARB with placebo, failed to demonstrate any cardiovascular protection by ARB. In two trials there was higher cardiovascular mortality in patients treated with ARB. Their putative beneficial effect in the prevention of atrial fibrillation was not confirmed in four major clinical trials specifically designed to investigate this effect. Moreover, in various recent trials, treatment with ARB led to worse renal outcomes, such as an increased incidence of microalbuminuria, renal impairment and decreased glomerular filtration rate. The role of ARB for the prevention of cardiovascular and renal disease should be re-examined. PMID- 22782922 TI - Weight loss and improved fitness slow down the decline in mobility in obese adults with type 2 diabetes. PMID- 22782923 TI - A comparison of the accuracy of clinical decisions based on full-text articles and on journal abstracts alone: a study among residents in a tertiary care hospital. AB - BACKGROUND: Many clinicians depend solely on journal abstracts to guide clinical decisions. OBJECTIVES: This study aims to determine if there are differences in the accuracy of responses to simulated cases between resident physicians provided with an abstract only and those with full-text articles. It also attempts to describe their information-seeking behaviour. METHODS: Seventy-seven resident physicians from four specialty departments of a tertiary care hospital completed a paper-based questionnaire with clinical simulation cases, then randomly assigned to two intervention groups-access to abstracts-only and access to both abstracts and full-text. While having access to medical literature, they completed an online version of the same questionnaire. FINDINGS: The average improvement across departments was not significantly different between the abstracts-only group and the full-text group (p=0.44), but when accounting for an interaction between intervention and department, the effect was significant (p=0.049) with improvement greater with full-text in the surgery department. Overall, the accuracy of responses was greater after the provision of either abstracts-only or full-text (p<0.0001). Although some residents indicated that 'accumulated knowledge' was sufficient to respond to the patient management questions, in most instances (83% of cases) they still sought medical literature. CONCLUSIONS: Our findings support studies that doctors will use evidence when convenient and current evidence improved clinical decisions. The accuracy of decisions improved after the provision of evidence. Clinical decisions guided by full-text articles were more accurate than those guided by abstracts alone, but the results seem to be driven by a significant difference in one department. PMID- 22782924 TI - Experimental approach to follow the spatiotemporal wood degradation in fungal microcosms. AB - To investigate the spatiotemporal growth dynamics in fungal microcosms and to follow the spatial degradation effects of fungal lignocellulose fermentation, a new and flexible experimental setup was developed and tested. White and brown rot fungi were cultivated under solid-state conditions in beech wood-filled silicon tubes for 5 weeks. After inoculation of wood material at one end of the tube, the culture vessels were aerated and moistured by flushing air through alkaline and aqueous solutions. After incubation, the silicon tubes were harvested and segmented to follow different growth and degradation parameters. This new approach holds great potential since it allows the use of different growth substrates, variable aeration or moisturization conditions and is therefore a useful tool for diverse degradation studies, e.g. respiration/mineralization studies involving flow meters or carbon dioxide sensors or for molecular biological approaches. PMID- 22782926 TI - Sialyl Lewis(x): a "pre-organized water oligomer"? AB - Organized and released: Sialyl Lewis(x) (sLe(x)) represents a "pre-organized water oligomer", that is, a surrogate for clustered water molecules attached to a scaffold. The impetus for sLe(x) binding to E-selectin is shown to be the high degree of pre-organization allowing an array of directed hydrogen bonds, and the entropic benefit of the release of water molecules from the large binding interface to bulk water (see picture). PMID- 22782928 TI - Pseudomonas putida PydR, a RutR-like transcriptional regulator, represses the dihydropyrimidine dehydrogenase gene in the pyrimidine reductive catabolic pathway. AB - The pyrimidine reductive catabolic pathway is important for the utilization of uracil and thymine as sources of nitrogen and carbon. The pathway is controlled by three enzymes: dihydropyrimidine dehydrogenase (DPD), dihydropyrimidinase and beta-alanine synthase. The putative DPD genes, pydX and pydA, are tandemly arranged in the Pseudomonas putida genome. Intriguingly, a putative transcriptional regulator, PydR, homologous to Escherichia coli RutR, a repressor of the Rut-dependent pyrimidine degradation pathway, is located downstream of pydX and pydA. In this study, we show that a pydA strain of P. putida fails to grow on a minimal media containing uracil or thymine as a sole nitrogen source, demonstrating the physiological importance of DPD in the reductive pathway. The expression of pydA and DPD activity in the absence of uracil were significantly higher in a pydR strain than in the wild-type strain, indicating that PydR acts as a repressor of the pyrimidine reductive pathway in P. putida. Phylogenetic analysis of RutR and PydR suggests that these homologous repressors may have evolved from a common ancestral protein that regulates pyrimidine degradation. PMID- 22782929 TI - Establishing a flow process to coumarin-8-carbaldehydes as important synthetic scaffolds. AB - Despite their usefulness as fluorophores and synthetic precursors, efficient and reliable routes to coumarin-8-carbaldehydes are lacking. We describe here a high yielding continuous flow synthesis that requires no manual intermediate purification or work-up, giving access to multigram quantities of the aldehyde product. PMID- 22782930 TI - Matrix solid-phase dispersion extraction for chromatographic analysis of labdane diterpenoids in Coleus forskohlii. AB - INTRODUCTION: The quality of Coleus forskohlii is often evaluated by high performance liquid chromatography (HPLC), using bioactive labdane diterpenoids as chemical markers. However, the existing sample preparation methods for the analysis of diterpenoids in C. forskohlii are generally labour-intensive, time consuming and require large volumes of solvents. OBJECTIVE: To establish an efficient matrix solid-phase dispersion (MSPD) extraction method for the simultaneous analysis of five bioactive diterpenoids in C. forskohlii by HPLC. METHODOLOGY: Herbal samples were prepared by an optimised MSPD procedure using C(18) as the sorbent. The quantification of the diterpenoids was achieved by HPLC with evaporative light scattering detector (ELSD), and the identification of the five compounds was performed by HPLC with tandem mass detector (MS/MS). The efficiency of the MSPD method was also compared with other extraction techniques including Soxhlet extraction, heat reflux extraction, ultrasonic-assisted extraction and microwave-assisted extraction. RESULTS: The MSPD extracted five diterpenoids with satisfactory recoveries ranging from 98.36% to 102.08%. Compared with other extraction methods, the proposed MSPD method had the advantages of combining extraction and clean-up into a single step, consuming less time and requiring lower solvent volumes. CONCLUSION: The MSPD method is simple, rapid and efficient for the extraction of labdane diterpenoids from C. forskohlii. The MSPD procedure coupled with HPLC-ELSD or HPLC-MS/MS is suitable for the quantification and identification of the diterpenoids in C. forskohlii. PMID- 22782931 TI - Emotional memory for central and peripheral details in children with callous unemotional traits. AB - A limited number of studies have shown that adults and adolescents with psychopathic traits suffer from emotional memory impairment. The present study examined whether this finding could be replicated in a sample of children between 8 and 12 years of age with callous-unemotional (CU) traits. Children with high CU traits (n=24) were compared with children with low CU traits (n=18) with regard to performance on a peripheral memory recognition test that examined memory for central and peripheral components of neutral and negative pictures. Results showed that overall recognition rates did not differ between the high- and low-CU groups. For negative pictures, both groups demonstrated better recognition of the central component at the expense of the peripheral component, while for neutral pictures, the peripheral component was better recognized than the central component. This study is the first to demonstrate that children with high CU traits do not suffer from an impaired emotional memory. PMID- 22782932 TI - Optimal administration routes for adipose-derived stem cells therapy in ischaemic flaps. AB - Improvement of flap survival represents an ongoing challenge in reconstructive surgery. The angiogenic potential of adipose-derived stem cells (ASCs) offers a promising approach to improve the viability of random pattern flaps. Recently, to maximize the therapeutic effects of ASCs, increasing focus is being placed on how to deliver the stem cells to target lesions. The purpose of the present study was to compare the effectiveness of different administration routes of ASCs to improve the viability of the random pattern skin flap. ASCs labelled with PKH26 were applied via four methods to the cranially-based random pattern skin flaps of rats: (a) intravenous injection; (b) subcutaneous injection; (c) application with collagen sponge seeding; and (d) application with fibrin glue seeding. ASCs led to a significant increase in flap viability in the subcutaneous injection group and the collagen sponge group. Cutaneous blood flow was increased in the intravenous injection, subcutaneous injection and collagen sponge groups. Capillary density in the intravenous injection group and collagen sponge group was significantly greater than in the control group (no treatment). PKH26 positive cells via the collagen sponge were distributed more densely within the flap than in other groups. This study demonstrated that the collagen sponge method delivered ASCs most effectively within the flap and increased flap vascularity. The clinical therapeutic effects of ASCs can therefore be maximized when the optimal delivery route is chosen. PMID- 22782933 TI - Is enantiomer assignment possible by NMR spectroscopy using residual dipolar couplings from chiral nonracemic alignment media?--A critical assessment. PMID- 22782934 TI - Detection of paeoniflorin and albiflorin by immunostaining technique using anti paeoniflorin monoclonal antibody. AB - INTRODUCTION: Paeoniae radix is one of the most important crude drugs used in Kampo medicines (KMs). A part of its pharmaceutical properties is due to the presence of paeoniflorin (PF) and albiflorin (AF). OBJECTIVE: For the specific and easy identification of PF and AF, an immunostaining technique was developed using anti-PF monoclonal antibody (MAb). METHODOLOGY: PF and AF were treated with a NaIO4 solution and reacted with bovine serum albumin (BSA) preparing PF- and AF BSA conjugates on the polyethersulphone (PES) membrane. Anti-PF MAb was bound and then antibody labelled with peroxidase directed against anti-PF MAb. Finally, a substrate was added and then PF and AF were detected. RESULTS: Anti-PF MAb recognised not only PF but also AF when 10 ug was present on the PES membrane. As little as 0.5 ug of PF and AF were still detected under immunostaining. Various Paeoniae radix samples and KMs were qualitatively analysed, and total amounts of PF and AF were visually detected by immunostaining technique. This method was applied to investigate the distribution of PF and AF in fresh peony root using immunoblotting by transferred from peony root to the PES membrane. CONCLUSION: The technique permitted the visualisation of PF and AF on PES membrane using immunostaining. The immunostaining technique established would be a powerful tool for probing the sources of PF and AF in plant extracts. PMID- 22782936 TI - Qualities of sessile serrated adenoma/polyp/lesion and its borderline variant in the context of synchronous colorectal carcinoma. AB - AIMS: Although much data have accumulated on sessile serrated adenoma/polyp/lesion (SSA/P/L) in general, its characteristics in specified contexts are less well elucidated. This lack of knowledge is even more conspicuous concerning its borderline counterpart, referred to as BSSA/P/L. The previous histological observations of the authors on SSA/P/L and BSSA/P/L in general are here extended to encompass attributes of these polyps in the context of synchronous colorectal carcinoma (SCRC), with a focus on the place of BSSA/P/L in the spectrum of non-dysplastic serrated polyps. METHODS: 219 SSA/P/Ls, 206 BSSA/P/Ls and 170 hyperplastic polyps (HPs) were examined for SCRC. Demographics, polyp details (size, site, BRAF((V600E))) and advanced synchronous conventional adenomas were recorded. RESULTS: SCRC was present in 12.3% of SSA/P/Ls, 7.1% of HPs (p=0.09) and 8.3% of BSSA/P/Ls. Patients' ages were comparable. Gender distribution of SSA/P/L and BSSA/P/L was equal, which differed, albeit insignificantly, from a male predominance of HPs. More SSA/P/Ls and BSSA/P/Ls than HPs exceeded 4 mm (p<=0.0001). A proximal site characterised SSA/P/L compared with BBSA/P/L and HP (p<0.0001). BRAF mutation was more prevalent in SSA/P/Ls and BSSA/P/Ls, which further coexisted with advanced synchronous conventional adenomas less commonly than HPs. CONCLUSIONS: BSSA/P/L was like SSA/P/L in most respects. The lower SCRC prevalence of BSSA/P/L could fit the idea of BSSA/P/L as a precursor to SSA/P/L, a notion that deserves attention when formulating guidelines for CRC screening. PMID- 22782937 TI - Enhanced bone regeneration by gelatin-beta-tricalcium phosphate composites enabling controlled release of bFGF. AB - The objective of this study was to investigate the feasibility of biodegradable gelatin-beta-tricalcium phosphate (beta-TCP) composites as a cell scaffold and controlled-release carrier of basic fibroblast growth factor (bFGF) suitable for inducing bone regeneration at a segmental bone defect. The composite of gelatin sponge and beta-TCP granules had an interconnected pore structure with an average size of 340 um. The composite provided the controlled release of bFGF over 2 weeks. Segmental, critical-sized, bone defects of 20 mm length were created in the ulnas of New Zealand white rabbits and the gelatin-beta-TCP composites, with or without incorporated bFGF, were implanted into the defects. Bone regeneration and beta-TCP resorption profiles were evaluated by microcomputed tomography scanner analysis and haematoxylin and eosin staining. The composites incorporating bFGF promoted significantly higher bone regeneration at the defect site as compared to the bFGF-free composites. The controlled release of biologically active bFGF from the composites may possibly be achieved through the biodegradation of the composites, resulting in the promotion of bone regeneration. We conclude that the biodegradable gelatin-beta-TCP composite is a promising scaffold for bone regeneration that enables the controlled release of bFGF. PMID- 22782938 TI - Unusual reversible photomechanical actuation in polymer/nanotube composites. AB - An azobenzene-containing liquid crystalline polymer/carbon nanotube composite strip was synthesized that shows rapid and reversible deformation under UV irradiation. The aligned nanotubes also provide the composite with much higher mechanical strength than pure liquid crystalline polymers and a very high electrical conductivity. PMID- 22782939 TI - Bone marrow stromal cells enhance the osteogenic properties of hydroxyapatite scaffolds by modulating the foreign body reaction. AB - We aimed to investigate the osteogenic properties of bone marrow stromal cell (BMSC)-loaded biomimetic constructs composed of hydroxyapatite (HA), with or without in vitro cell-derived extracellular matrix (HA-ECM), and to assess the cellular components of the elicited foreign body reaction. HA-ECM constructs were produced by adult rat dermal fibroblasts cultured on top of synthetic HA microparticles. Rat calvarial critical-sized defects (8 mm) were created and treated with the generated HA-ECM constructs or HA microparticles, alone or combined with green fluorescent protein (GFP)-expressing BMSCs. The new bone formation and the local cellular inflammatory response (macrophages, neutrophils, lymphocytes, eosinophils and PCNA-index) were assessed by histomorphometry and immunohistochemistry at 2 and 12 weeks postoperatively. In addition, the BMSCs' survival and engraftment were checked. The largest volume of the newly formed bone was found in defects treated with HA-ECM constructs combined with BMSCs (p < 0.05). Moreover, the implanted BMSCs modulated the local inflammatory response, demonstrated by either a significant increase (HA vs HA + BMSCs) or decrease (HA ECM vs HA-ECM + BMSCs) of the inflammatory cell number. No donor BMSCs were detected at the site of implantation or in the host bone marrow at 2 or 12 weeks postoperatively. In conclusion, the treatment of critical-sized calvarial defects with the BMSC-loaded biomimetic constructs has significantly enhanced bone repair by modulating the foreign body reaction. Our findings highlight the implications of BMSCs in the regulation of the foreign body reaction triggered by tissue engineered constructs, proving a higher efficiency for the BMSC combination therapy. PMID- 22782940 TI - Heterolytic outer-sphere cleavage of H2 for the reduction of N2 in the coordination sphere of transition metals--a DFT study. PMID- 22782942 TI - Left main artery compression by pulmonary artery aneurysm and ostial athero stenosis of left anterior descending artery in a young female with pulmonary arterial hypertension. PMID- 22782941 TI - Left atrial structure and function and clinical outcomes in the general population. AB - AIMS: Left atrial (LA) structural and functional abnormalities may be subclinical phenotypes, which identify individuals at increased risk of adverse outcomes. METHODS AND RESULTS: Maximum LA volume (LAmax) and LA emptying fraction (LAEF) were measured via cardiac magnetic resonance imaging in 1802 participants in the Dallas Heart Study. The associations of LAEF and LAmax indexed to body surface area (LAmax/BSA) with traditional risk factors, natriuretic peptide levels, and left ventricular (LV) structure [end-diastolic volume (EDV) and concentricity(0.67) (mass/EDV(0.67))] and function (ejection fraction) were assessed using linear regression analysis. The incremental prognostic value of LAmax/BSA and LAEF beyond traditional risk factors, LV ejection fraction, and LV mass was assessed using the Cox proportional-hazards model. Both increasing LAmax/BSA and decreasing LAEF were associated with hypertension and natriuretic peptide levels (P < 0.05 for all). In multivariable analysis, LAmax/BSA was most strongly associated with LV end-diastolic volume/BSA, while LAEF was strongly associated with LV ejection fraction and concentricity(0.67). During a median follow-up period of 8.1 years, there were 81 total deaths. Decreasing LAEF [hazard ratio (HR) per 1 standard deviation (SD) (8.0%): 1.56 (1.32-1.87)] but not increasing LAmax/BSA [HR per 1 SD (8.6 mL/m(2)): 1.14 (0.97-1.34)] was independently associated with mortality. Furthermore, the addition of LAEF to a model adjusting Framingham risk score, diabetes, race, LV mass, and ejection fraction improved the c-statistic (c-statistics: 0.78 vs. 0.77; P < 0.05, respectively), whereas the addition of LAmax/BSA did not (c-statistics: 0.76, P = 0.20). CONCLUSION: In the general population, both LAmax/BSA and LAEF are important subclinical phenotypes but LAEF is superior and incremental to LAmax/BSA. PMID- 22782943 TI - Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications, and prognostic impact: multicentre registry study of the Japanese Coronary Spasm Association. AB - AIMS: Provocation tests of coronary artery spasm are useful for the diagnosis of vasospastic angina (VSA). However, these tests are thought to have a potential risk of arrhythmic complications, including ventricular tachycardia (VT), ventricular fibrillation (VF), and brady-arrhythmias. We aimed to elucidate the safety and the clinical implications of the spasm provocation tests in the nationwide multicentre registry study by the Japanese Coronary Spasm Association. METHODS AND RESULTS: A total of 1244 VSA patients (M/F, 938/306; median 66 years) who underwent the spasm provocation tests were enrolled from 47 institutes. The primary endpoint was defined as major adverse cardiac events (MACEs). The provocation tests were performed with either acetylcholine (ACh, 57%) or ergonovine (40%). During the provocation tests, VT/VF and brady-arrhythmias developed at a rate of 3.2 and 2.7%, respectively. Overall incidence of arrhythmic complications was 6.8%, a comparable incidence of those during spontaneous angina attack (7.0%). Multivariable logistic regression analysis demonstrated that diffuse right coronary artery spasm (P < 0.01) and the use of ACh (P < 0.05) had a significant correlation with provocation-related VT/VF. During the median follow-up of 32 months, 69 patients (5.5%) reached the primary endpoint. The multivariable Cox proportional hazard model revealed that mixed (focal plus diffuse) type multivessel spasm had an important association with MACEs (adjusted hazard ratio, 2.84; 95% confidence interval, 1.34-6.03; P < 0.01), whereas provocation-related arrhythmias did not. CONCLUSION: The spasm provocation tests have an acceptable level of safety and the evaluation of spasm type may provide useful information for the risk prediction of VSA patients. PMID- 22782944 TI - Cardiac resident progenitor cells: evidence and functional significance. PMID- 22782945 TI - Severe mitral regurgitation in patients with postinfarction interventricular septal defect: a simple way of simultaneous valve repair. AB - Ventricular septal defect, a potentially deadly complication of transmural myocardial infarction, is often accompanied by ischaemic mitral regurgitation. It has been recognized that the presence and persistence of the latter negatively affect survival rates in patients after myocardial infarction. We present a simple endoventricular edge-to-edge technique of mitral repair using a single U shaped stitch of polytetrafluoroethylene and a refined double-patch 'exclusion' technique of postinfarction interventricular septal defect (PVSD) closure in the treatment of two consecutive cases of PVSD and concomitant ischaemic mitral regurgitation. This technique is effective and reproducible to address mitral incompetence in patients undergoing surgical correction of PVSD. PMID- 22782946 TI - Dengue research opportunities in the Americas. AB - Dengue is a systemic arthropod-borne viral disease of major global public health importance. At least 2.5 billion people who live in areas of the world where dengue occurs are at risk of developing dengue fever (DF) and its severe complications, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Repeated reemergences of dengue in sudden explosive epidemics often cause public alarm and seriously stress healthcare systems. The control of dengue is further challenged by the lack of effective therapies, vaccines, and point-of-care diagnostics. Despite years of study, even its pathogenic mechanisms are poorly understood. This article discusses recent advances in dengue research and identifies challenging gaps in research on dengue clinical evaluation, diagnostics, epidemiology, immunology, therapeutics, vaccinology/clinical trials research, vector biology, and vector ecology. Although dengue is a major global tropical pathogen, epidemiologic and disease control considerations in this article emphasize dengue in the Americas. PMID- 22782947 TI - In vivo emergence of Aspergillus terreus with reduced azole susceptibility and a Cyp51a M217I alteration. AB - Azole resistance in Aspergillus terreus isolates was explored. Twenty related (MB) and 6 unrelated A. terreus isolates were included. CYP51A sequencing and RAPD genotyping was performed. Five MB isolates were itraconazole susceptible, whereas the minimum inhibitory concentrations (MICs) for 15 MB isolates were elevated (1-2 mg/L). Voriconazole and posaconazole MICs were 0.5-4 and 0.06-0.5 mg/L, respectively, for MB isolates but 0.25-0.5 and <0.03-0.06 mg/L, respectively, for controls. Sequencing identified a Cyp51Ap M217I alteration in all 15 isolates with elevated itraconazole MICs. Genotyping showed that 18 of 20 MB isolates were identical and unique, suggesting endogenous origin. In conclusion, itraconazole resistance in A. terreus was linked to an M217I Cyp51A alteration. PMID- 22782948 TI - Baseline levels of soluble CD14 and CD16+56- natural killer cells are negatively associated with response to interferon/ribavirin therapy during HCV-HIV-1 coinfection. AB - Disease progression of human immunodeficiency virus type 1 (HIV-1) is associated with immune activation. Activation indices are higher during coinfection of hepatitis C virus (HCV) and HIV. The effect of immune activation on interferon alpha (IFN-alpha) therapy response is unknown. We evaluated soluble CD14 (sCD14) and natural killer (NK)-cell subsets at baseline, and during pegIFN alpha2a/ribavirin therapy in HCV-HIV coinfection. The sCD14 level increased during therapy. Baseline sCD14 positively correlated with baseline HCV level and CD16(+)56(-) NK-cell frequency, and both sCD14 and CD16(+)56(-) NK cells correlated negatively with magnitude of HCV decline. IL28B genotype was associated with therapy response but not sCD14 or CD16(+)56(-) NK frequency. Markers of innate immune activation predict poor host response to IFN-alpha-based HCV therapy during HCV-HIV coinfection. PMID- 22782949 TI - Immunogenicity and safety of varying dosages of a monovalent 2009 H1N1 influenza vaccine given with and without AS03 adjuvant system in healthy adults and older persons. AB - BACKGROUND: Adjuvanted vaccines have the potential to improve influenza pandemic response. AS03 adjuvant has been shown to enhance the immune response to inactivated influenza vaccines. METHODS: This trial was designed to evaluate the immunogenicity and safety of an inactivated 2009 H1N1 influenza vaccine at varying dosages of hemagglutinin with and without extemporaneously mixed AS03 adjuvant system in adults >= 18 years of age. Adults were randomized to receive 2 doses of 1 of 5 vaccine formulations (3.75 ug, 7.5 ug, or 15 ug with AS03 or 7.5 ug or 15 ug without adjuvant). RESULTS: The study population included 544 persons <65 years of age and 245 persons >= 65 years of age. Local adverse events tended to be more frequent in the adjuvanted vaccine groups, but severe reactions were uncommon. In both age groups, hemagglutination inhibition antibody geometric mean titers after dose one were higher in the adjuvanted groups, compared with the 15 ug unadjuvanted group, and this difference was statistically significant for the comparison of the 15 ug adjuvanted group with the 15 ug unadjuvanted group. CONCLUSIONS: AS03 adjuvant system improves the immune response to inactivated 2009 H1N1 influenza vaccine in both younger and older adults and is generally well tolerated. ClinicalTrials.gov NCT00963157. PMID- 22782950 TI - Hepatitis B surface antigen declines and clearance during long-term tenofovir therapy in patients coinfected with HBV and HIV. AB - BACKGROUND: The kinetics of hepatitis B surface antigen (HBsAg) are predictive in HBV-infected patients treated with pegylated interferon. Knowledge about the value of HBsAg levels in patients coinfected with HBV and human immunodeficiency virus (HIV) is lacking. METHODS: We quantified serum HBsAg in a Dutch multicenter cohort of 104 patients coinfected with HIV and HBV who were treated with tenofovir disoproxil fumarate (TDF) as part of highly active antiretroviral therapy. The median duration of therapy was 57 months (interquartile range, 34-72 months). RESULTS: Hepatitis B e antigen (HBeAg)-positive patients achieved a decline of 2.2 log IU/mL in HBsAg, whereas HBeAg-negative patients only achieved a decline of 0.6 log IU/mL during 6 years of TDF therapy. Declines in HBsAg at months 6 and 12 correlated with CD4 cell count for HBeAg-positive patients. Five HBeAg-positive patients (8%) and 3 HBeAg-negative patients (8%) cleared HBsAg. HBeAg-negative patients who cleared HBsAg had lower baseline HBsAg as compared to patients who remained HBsAg positive. The majority of patients who cleared HBsAg achieved this end point within the first year. In HBeAg-positive patients, decline in HBsAg at month 6 was predictive of achieving HBsAg seroclearance. CONCLUSIONS: Receipt of TDF therapy by HIV/HBV-coinfected patients for up to 6 years led to a significant decrease in HBsAg in the HBeAg-positive population. HBsAg kinetics early during treatment were predictive of HBsAg seroclearance and correlated with an increased CD4 cell count, underlining the importance of immune restoration in HBV clearance. PMID- 22782951 TI - Protecting adults from influenza: tis the season to learn from the pandemic. PMID- 22782952 TI - Toll-like receptor 2 deficiency increases resistance to Pseudomonas aeruginosa pneumonia in the setting of sepsis-induced immune dysfunction. AB - BACKGROUND: Sepsis is characterized by a dysregulated inflammatory response followed by immunosuppression that favors the development of secondary infections. Toll-like receptors (TLRs) are major regulators of the host's response to infections. How variability in TLR signaling may impact the development of sepsis-induced immune dysfunction has not been established. We sought to establish the role of TLR2, TLR4, and TLR5 in postseptic mice with Pseudomonas aeruginosa pneumonia. METHODS: We used an experimental model of sublethal polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wild type, tlr2(-/-), tlr4(-/-), tlr5(-/-), tlr2 4(-/-) mice that underwent CLP were secondarily subjected to P. aeruginosa pulmonary infection. RESULTS: Postseptic wild-type and tlr4(-/-) and tlr5(-/-) mice displayed high susceptibility to P. aeruginosa pneumonia. In contrast, TLR2-deficient mice, either tlr2(-/-)or tlr2 4(-/-), that underwent CLP were resistant to the secondary pulmonary infection. As compared to wild-type mice, tlr2(-/-) mice displayed improvement in bacterial clearance, decreased bacteremic dissemination, and attenuated lung damage. Furthermore, tlr2(-/-) mice exhibited a pulmonary proinflammatory cytokine balance, with increased production of tumor necrosis factor alpha and decreased release of interleukin 10. CONCLUSIONS: In a model of secondary P. aeruginosa pneumonia in postseptic mice, TLR2 deficiency improves survival by promoting efficient bacterial clearance and restoring a proinflammatory cytokine balance in the lung. PMID- 22782953 TI - Serologic reactivity to the emerging pathogen Granulibacter bethesdensis. AB - BACKGROUND: Granulibacter bethesdensis is a recently described member of the Acetobacteraceae family that has been isolated from patients with chronic granulomatous disease (CGD). Its pathogenesis, environmental reservoir(s), and incidence of infection among CGD patients and the general population are unknown. METHODS: Detected antigens were identified by mass spectroscopy after 2 dimensional electrophoresis and immunoaffinity chromatography. The prevalence of Granulibacter immunoreactivity was assessed through immunoblotting and enzyme linked immunosorbent assay (ELISA). RESULTS: Methanol dehydrogenase (MDH) and formaldehyde-activating enzyme were recognized during analysis of sera from infected patients. Unique patterns of immunoreactive bands were identified in Granulibacter extracts, compared with extracts of other Acetobacteraceae species. By use of criteria based on these specific bands, specimens from 79 of 175 CGD patients (45.1%) and 23 of 93 healthy donors (24.7%) reacted to all 11 bands. An ELISA that used native MDH to capture and detect immunoglobulin G was developed and revealed high-titer MDH seroreactivity in culture-confirmed cases and 5 additional CGD patients. Testing of samples collected prior to culture-confirmed infection demonstrated instances of recent seroconversion, as well as sustained seropositivity. Infection of CGD mice with G. bethesdensis confirmed acquisition of high-titer antibody-recognizing MDH. CONCLUSIONS: These serologic tests suggest that Granulibacter immunoreactivity is more common among CGD patients and, perhaps, among healthy donors than was previously suspected. This finding raises the possibility that clinical presentations of Granulibacter infection may be underappreciated. PMID- 22782954 TI - The PavA-like fibronectin-binding protein of Enterococcus faecalis, EfbA, is important for virulence in a mouse model of ascending urinary tract infection. AB - Enterococcus faecalis is an established nosocomial pathogen, yet the pathogenesis of enterococcal infections, particularly of urinary tract infections (UTIs), remains to be fully elucidated. Fibronectin-binding proteins have been identified as potent adhesins in pathogenic Gram-positive cocci. Here, we characterized EfbA, which is encoded by the enterococcal orthologue of Streptococcus pneumoniae pavA. Similar to PavA, the anchorless EfbA protein was localized to the enterococcal cell outer surface and bound to immobilized human fibronectin. In addition to abrogated EfbA expression, deletion of the efbA gene eliminated EfbA from the cell surface and drastically reduced the enterococcal cell binding to immobilized fibronectin. The DeltaefbA deletion mutant was highly attenuated vs wild-type in a murine ascending UTI model, consistent with an increased tropism for the kidney relative to the bladder. These results provide the first evidence that EfbA of E. faecalis plays a role in UTIs, probably contributing to the pathogenesis in this site. PMID- 22782955 TI - Altered left ventricular longitudinal diastolic function correlates with reduced systolic function immediately after anthracycline chemotherapy. AB - AIMS: The benefits from anthracycline chemotherapy are undermined by potentially life-threatening cardiotoxicity. Transthoracic echocardiography is the most commonly used method for monitoring cardiotoxicity, and centres on the measurement of left ventricular systolic function. The aim of this study was to utilize two-dimensional speckle tracking echocardiography (2DSTE) at baseline and immediately after anthracycline chemotherapy to investigate whether patients with significant changes in systolic function after anthracycline therapy would also develop alterations in diastolic parameters. METHODS AND RESULTS: Fifty-two women with histologically confirmed breast cancer were prospectively recruited. Echocardiograms were performed 1 week prior to and 1 week following chemotherapy (always before adjuvant trastuzumab or thoracic radiotherapy). Conventional Doppler, tissue velocity imaging (TVI), and 2DSTE were used to measure diastolic function. 2DSTE measurements included longitudinal diastolic strain, early (E Sr), and late (A-Sr) myocardial strain rate. 2DSTE and left ventricular ejection fraction (LVEF) were used to measure longitudinal systolic function. Altered LV diastolic function (including E-Sr) was observed in the entire cohort after chemotherapy, with a differential reduction in participants with a post therapy LVEF <55%. Pre-chemotherapy systolic strain was found to predict reduced E-Sr post therapy (P = 0.04). Univariate predictors of E-Sr were LVEF post therapy (P = 0.049) and systolic strain post-therapy (P = 0.01). In a multivariate analysis, systolic strain after chemotherapy was the strongest independent predictor (P = 0.001). CONCLUSION: Altered LV diastolic function was observed immediately after the administration of therapeutic doses of anthracycline chemotherapy. Furthermore, our analysis indicates that the changes in diastolic function are associated with reduced systolic function. PMID- 22782956 TI - Defining the magnitude of measurement variability in the virtual histology analysis of acute coronary syndrome plaques. AB - BACKGROUND: Previous intravascular ultrasound-based virtual histology (IVUS-VH) measurement variability studies have been confined to single-frame or short segment analysis in stable patients with minimal disease. We sought to determine the magnitude of human measurement variability in acute coronary syndrome (ACS) plaques. METHODS AND RESULTS: Prior to percutaneous coronary intervention, we performed IVUS-VH analysis in troponin-positive ACS culprit lesions. A total of 3840 IVUS-VH frames were analysed by two operators to determine intra- and inter observer variability. The plaque constituent area and volumes were compared using intra-class correlation coefficient (ICC); within-subjects standard deviation (WSSD, mm(2) or mm(3)) and the repeatability coefficient (RCO) to quantify the magnitude of operator error that 95% of future measurements should not exceed. The majority of intra- and inter-observer measurements had ICC of >0.92 confirming excellent agreement. Only the fibrous area (0.86), fibro-fatty (FF) area (0.72) and FF volume (0.87) had ICC levels suggesting an operator error >10%. However, the mean RCO and the percentage this represents in single-frame analysis (area error) varied across the plaque subtypes: fibrous area = 1.64 mm(2) (59%); FF area = 0.49 mm(2) (140%); necrotic core (NC) area = 0.39 mm(2) (21.3%); dense calcium (DC) area = 0.29 mm(2) (33.7%). For full lesion pullbacks (volume error): fibrous volume = 8.14 mm(3) (9.9%); FF volume = 5.63 mm(3) (53.8%); NC volume = 3.78 mm(3) (6.9%) and DC = 2.4 mm(3) (9.6%) CONCLUSION: As in previous studies, intra- and inter-observer ICC suggests good agreement between observers. However, this can still represent large measurement error values and percentages. These findings could impact on the interpretation of previous studies and influence future studies using IVUS-VH measurements as endpoints. PMID- 22782957 TI - Role of dyssynchrony in optimization of CRT implantation: a time to re-think? PMID- 22782958 TI - Longitudinal right ventricular function is a better predictor of right ventricular contribution to exercise performance than global or outflow tract ejection fraction in tetralogy of Fallot: a combined echocardiography and magnetic resonance study. AB - AIMS: The contribution of the systolic function of the right ventricular (RV) outflow tract (RVOT) and of longitudinal shortening of the body of the right ventricle to global RV systolic function and exercise capacity in patients after tetralogy of Fallot (TOF) repair is unclear. Our aim was to characterize the functional role of the RVOT and to identify the most suitable method of assessing RV systolic function in clinical practice. METHODS: The cardiac magnetic resonance (CMR) studies, echocardiograms, and medical records of 50 consecutive patients with repaired TOF who underwent CMR were reviewed. The volumes of the RVOT and of the remainder of the RV were measured separately. Echocardiographic RV strain measurements based on ultrasound speckle tracking were collected. RESULTS: After excluding the akinetic RVOT, RVEF was statistically higher (47.1 vs. 45.0%, P< 0.0001) but the average increase in EF was small. The correlations of fractional area change and global longitudinal strain, both by echocardiography, with global RVEF were moderate (r= 0.59, P= 0.0001 and r= 0.56, P= 0.0004, respectively). The correlation between RVEF and predicted maximal oxygen consumption (VO(2)max-predicted) was weak, regardless of whether the akinetic RVOT was included or not (r= 0.33, P= 0.049 and r= 0.36, P= 0.03, respectively). Of all imaging parameters, echocardiographic RV longitudinal strain correlated best with VO(2)max-predicted (r= 0.66, P= 0.0001). CONCLUSIONS: In patients following TOF repair, echocardiographic and CMR descriptors of global RV systolic function are, at best, weak predictors of exercise tolerance. Longitudinal function of the RV, measured remotely from the RVOT, may be a more important determinant of exercise performance than global RVEF in patients with aneurismal RVOTs. PMID- 22782959 TI - Gemcitabine-induced pleuropericardial effusion in a patient with pancreatic cancer. AB - Pleuropericardial effusion is an extremely rare complication of gemcitabine chemotherapy. The patient was a 56-year-old woman administered systemic chemotherapy with gemcitabine for local recurrence of pancreatic cancer and lymph node metastasis developing 4 years after pancreaticoduodenectomy. Four months after the start of the chemotherapy, she presented with exertional dyspnea and edema in both her legs and face. Echocardiography and computed tomography revealed pericardial and bilateral pleural effusion. A pericardiocentesis was immediately performed to prevent the development of cardiac tamponade as well as to examine the cause of the pericardial effusion. As a result, the patient's exertional dyspnea and edema resolved. No metastases to the thorax or mediastinum were noted. A cytological study of the pericardial and pleural effusions revealed no malignant cells. Cultures for bacteria, mycobacteria and fungi were negative. Tests for autoantibodies indicating autoimmune disease were also negative, and hormonal assays for the detection of endocrine disease were normal. She was followed up after discontinuation of the gemcitabine treatment, and no further episodes of pericardial or pleural effusion occurred. Thus, it is speculated that the pericardial effusion and bilateral pleural effusion may have been caused by gemcitabine. PMID- 22782960 TI - Multicenter feasibility study of combination therapy with fluorouracil, leucovorin and paclitaxel (FLTAX) for peritoneal disseminated gastric cancer with massive ascites or inadequate oral intake. AB - OBJECTIVE: Oral fluoropyrimidine plus cisplatin is a standard treatment for advanced gastric cancer, but patients with severe peritoneal metastasis often cannot tolerate this regimen. The aim of this study was to assess the feasibility of fluorouracil, l-leucovorin and paclitaxel therapy in such patients. METHODS: In the first phase of the study, we investigated the maximum tolerated dose and recommended dose in Cycle 1 of fluorouracil, l-leucovorin and paclitaxel, at two dose levels [Level 1 (n = 6): 5-fluorouracil/l-leucovorin/paclitaxel = 500/250/60 mg/m(2); Level 2 (n = 6): 600/250/80 mg/m(2) on Days 1, 8 and 15, every 28 days]. Nineteen additional patients at the recommended dose level were enrolled in the second phase to investigate the feasibility of fluorouracil, l-leucovorin and paclitaxel therapy. The primary endpoint in the second phase was the completion rate of two cycles. RESULTS: Dose-limiting toxicities were observed in a patient at Level 1 with Grade 4 gastrointestinal perforation (the site of primary tumor), and in two patients at Level 2 with Grade 3 febrile neutropenia and Grade 3 infection, respectively. In Cycle 2, treatment-related death occurred at Level 2 in one patient who had Grade 4 febrile neutropenia with pneumonia. The maximum tolerated dose was set at Level 2, and the recommended dose was determined as Level 1. In the second phase, the completion rate of two cycles was 92% and the ascites response was 44%. Median progression-free survival was 4.2 months and overall survival was 8.0 months. Grade 3/4 neutropenia was observed in 12% of patients. CONCLUSIONS: Fluorouracil, l-leucovorin and paclitaxel at Level 1 is feasible as first-line treatment for peritoneal disseminated gastric cancer patients with massive ascites or inadequate oral intake. PMID- 22782961 TI - High incidence of hepatocellular carcinoma in ESRD patients: caused by high hepatitis rate or 'uremia'? a population-based study. AB - OBJECTIVE: A high incidence of hepatocellular carcinoma has been reported in end stage renal disease patients. This study was undertaken to evaluate whether this was caused by a high rate hepatitis or 'uremia' per se. METHODS: We used claims data of the Bureau of National Health Insurance of Taiwan for analysis. All patients diagnosed with end-stage renal disease having received their first dialysis between 1 January 2003 and 31 December 2007 (n = 38 714) were enrolled for the study. A database of 1 million randomly selected subjects matched for age, gender, hepatitis B and C infection, and liver cirrhosis for the same period was used as control (n = 38 714). The longest observation period was up to 31 December 2008. RESULTS: There was no significant difference in the incidence of hepatocellular carcinoma between end-stage renal disease patients and their non end-stage renal disease counterparts (2.03 per 1000 person-years vs. 2.10 per 1000 person-years, rate ratio = 0.947; 95% confidence interval: 0.792-1.132). End stage renal disease patients with hepatocellular carcinoma had higher percentages of diabetes mellitus, hypertension, heart failure and gout (all P < 0.001), and they presented with a worse cumulative survival rate than the non-end-stage renal disease group (P < 0.001). End-stage renal disease patients developing hepatocellular carcinoma were younger, and had more comorbidities than their non end-stage renal disease counterparts. End-stage renal disease (hazard ratio = 1.61) and diabetes mellitus (hazard ratio = 1.55) were found to be independent factors for mortality in hepatocellular carcinoma patients. CONCLUSIONS: After matching for hepatitis and liver cirrhosis, end-stage renal disease is not associated with a higher incidence of hepatocellular carcinoma than the general population. The high incidence of hepatocellular carcinoma in end-stage renal disease patients was caused by a high viral hepatitis rate rather than 'uremia' per se. Owing to increased comorbidity, end-stage renal disease patients developing hepatocellular carcinoma had worse long-term survival than non-end stage renal disease patients. PMID- 22782962 TI - Erythema multiforme induced by sorafenib for metastatic renal cell carcinoma. AB - OBJECTIVE: Sorafenib is one of the few standard agents for metastatic renal cell carcinoma. Although sorafenib-induced erythema multiforme is rarely reported, we evaluated the cases of erythema multiforme induced by sorafenib for metastatic renal cell carcinoma. METHODS: From November 2006 to November 2011, 36 eligible patients who had been treated with sorafenib were enrolled in this study. Patients received sorafenib 200 or 400 mg orally, twice daily, at 12 h intervals, on a continuous dosing schedule. All patients who experienced rash or erythema multiforme underwent a skin biopsy, and the histopathological diagnosis was confirmed. RESULTS: Twenty-eight patients (78%) experienced a skin reaction of any toxicity grade. Hand-foot skin reactions occurred in 17 (47%), erythema multiforme in 9 (25%), rash/desquamation in 6 (17%) and alopecia in 9 (25%). Skin biopsy was performed and histopathological diagnosis was confirmed for all nine patients (25%) who experienced erythema multiforme. All nine showed a positive reaction to sorafenib on a subsequent patch test. CONCLUSIONS: Sorafenib-induced erythema multiforme may not be rare in Japanese patients. Patients who once showed erythema multiforme after sorafenib treatment are never to be treated with sorafenib again. Patients treated with sorafenib should be monitored carefully, with a multidisciplinary approach. Consultation with a dermatologist is critical because some cases quickly become severe. PMID- 22782964 TI - Management of ureteral obstruction in advanced testicular tumor with lymph node metastasis. AB - OBJECTIVE: Ureteral obstruction is one of the complications of testicular tumor with retroperitoneal lymph node metastasis that requires ureteral stenting for management. We elucidated the clinical courses of ureteral obstructions and changes in renal functions in patients with indwelling ureteral stenting. METHODS: The medical records of 56 patients who were treated for metastatic testicular tumors by chemotherapy at a single institute between 2002 and 2010 were retrospectively reviewed. RESULTS: Among 56 patients, 12 patients needed ureteral stenting before chemotherapy. The proportion of patients requiring ureteral stenting was significantly higher in seminoma than non-seminoma (47 and 12%, respectively, P < 0.05). The ureteral stent was removed after chemotherapy or retroperitoneal lymph node dissection in all patients, except for one patient who died of cancer during chemotherapy. At retroperitoneal lymph node dissection, ureters were spared in three patients, a partial ureterectomy was needed in one patient, and no case underwent adjunctive nephrectomy. These 11 patients presented no local and distant recurrence at median follow-up of 44 months. Ureteral stenting increased the estimated glomerular filtration rate to more than 60 ml/min before chemotherapy in all patients, but it decreased to <60 ml/min in 6 of 11 patients after chemotherapy. CONCLUSIONS: Ureteral obstruction due to testicular tumor was relieved after chemotherapy or retroperitoneal lymph node dissection. Ureteral stenting was effective to improve renal function before chemotherapy, although we should pay special attention to deterioration of renal function during or after chemotherapy. PMID- 22782963 TI - Analysis of Intravesical Recurrence After Bladder-preserving Therapy for Muscle invasive Bladder Cancer. AB - OBJECTIVE: The aim of the present study was to analyze the pattern of recurrences after bladder-preserving therapy for muscle-invasive bladder cancer. METHODS: The subjects were 77 patients with T2-3N0M0 bladder cancer whose bladder was preserved by intra-arterial chemotherapy and radiation. The patterns of the first recurrences were retrospectively analyzed. RESULTS: With a median follow-up of 38.5 months, 17 patients (22.1%) experienced intravesical recurrence without metastasis, 14 (82.4%) of which were cases of non-muscle-invasive bladder cancer recurrence and 3 (17.6%) of which were muscle-invasive bladder cancer recurrences. Muscle-invasive bladder cancer recurred at the same site as the initial tumor site in all three cases, whereas non-muscle-invasive bladder cancer recurred at different sites in 64% of the patients in that group. The peak hazard of the non-muscle-invasive bladder cancer recurrence was observed at around a year after treatment. Recurrent non-muscle-invasive bladder cancer was of a significantly lower histological grade with lower Ki-67-labeling indices than the initial muscle-invasive bladder cancer. Twelve (85.7%) of 14 patients with non muscle-invasive bladder cancer recurrence achieved disease-free status. The multivariate analysis revealed that multiplicity, grade and tumor size were significantly correlated with the recurrence (P= 0.0001, 0.0442 and 0.0412, respectively). CONCLUSIONS: Most of the recurrences after bladder-preserving therapy were cases of non-muscle-invasive bladder cancer. The recurrence pattern and characteristics of the tumors did not differ from those of primary non-muscle invasive bladder cancer. Patients with high-risk factors would be candidates for prophylactic intravesical therapy for non-muscle-invasive bladder cancer recurrence. PMID- 22782965 TI - The incidence and significance of retropharyngeal lymph node metastases in hypopharyngeal cancer. AB - OBJECTIVE: To evaluate the incidence and clinical significance of retropharyngeal lymph node metastasis in hypopharyngeal cancer. METHODS: Pretreatment computed tomography and/or magnetic resonance images of 152 patients treated between 1998 and 2009 were retrospectively reviewed. The prognostic significance of retropharyngeal lymph node metastasis for 116 patients who received definitive treatment was also analyzed. RESULTS: Twelve patients (8%) were radiologically positive for retropharyngeal lymph node metastasis. Tumors originating from the posterior wall showed significantly higher incidence of retropharyngeal lymph node than those originating from other sites (23.8 vs. 5.3%, P = 0.01). The majority of patients with retropharyngeal lymph node involvement experienced distant metastasis. The overall survival rate of patients with retropharyngeal lymph node metastasis was worse than in those lacking retropharyngeal lymph node involvement (0 vs. 68.8% at 2 years, P < 0.01), and so was the cause-specific survival rate (0 vs. 74% at 2 years, P < 0.01). CONCLUSIONS: Patients with hypopharyngeal cancer, especially those with posterior wall tumors, are at high risk for retropharyngeal lymph node involvement. Patients with retropharyngeal lymph node metastasis developed distant metastasis frequently, and showed dismal outcomes. PMID- 22782967 TI - Induction of Bcl-3 by acute binge alcohol results in toll-like receptor 4/LPS tolerance. AB - Acute alcohol binge results in immunosuppression and impaired production of proinflammatory cytokines, including TNF-alpha. TNF-alpha production is induced by LPS, a TLR4 ligand, and is tightly regulated at various levels of the signaling cascade, including the NF-kappaB transcription factor. Here, we hypothesized that acute alcohol induces TLR4/LPS tolerance via Bcl-3, a nuclear protein and member of the NF-kappaB family. We found that acute alcohol pretreatment resulted in the same attenuating effect as LPS pretreatment on TLR4 induced TNF-alpha production in human monocytes and murine RAW 264.7 macrophages. Acute alcohol-induced Bcl-3 expression and IP studies revealed increased association of Bcl-3 with NF-kappaB p50 homodimers in alcohol-treated macrophages and in mice. ChIP assays revealed increased occupancy of Bcl-3 and p50 at the promoter region of TNF-alpha in alcohol-pretreated cells. To confirm that the Bcl 3-p50 complex regulates transcription/production of TNF-alpha during acute alcohol exposure, we inhibited Bcl-3 expression using a targeted siRNA. Bcl-3 knockdown prevented the alcohol-induced inhibition of TNF-alpha mRNA and protein production. In a mouse model of binge alcohol, an increase in Bcl-3 and a concomitant decrease in TNF-alpha but no change in IL-10 production were found in mice that received alcohol followed by LPS challenge. In summary, our novel data suggest that acute alcohol treatment in vitro and in vivo induces molecular signatures of TLR4/LPS tolerance through the induction of Bcl-3, a negative regulator of TNF-alpha transcription via its association with NF-kappaB p50/p50 dimers. PMID- 22782966 TI - Regulation of inflammation by interleukin-4: a review of "alternatives". AB - Studies of IL-4 have revealed a wealth of information on the diverse roles of this cytokine in homeostatic regulation and disease pathogenesis. Recent data suggest that instead of simple linear regulatory pathways, IL-4 drives regulation that is full of alternatives. In addition to the well-known dichotomous regulation of Th cell differentiation by IL-4, this cytokine is engaged in several other alternative pathways. Its own production involves alternative mRNA splicing, yielding at least two functional isoforms: full-length IL-4, encoded by the IL-4 gene exons 1-4, and IL-4delta2, encoded by exons 1, 3, and 4. The functional effects of these two isoforms are in some ways similar but in other ways quite distinct. When binding to the surface of target cells, IL-4 may differentially engage two different types of receptors. By acting on macrophages, a cell type critically involved in inflammation, IL-4 induces the so-called alternative macrophage activation. In this review, recent advances in understanding these three IL-4-related branch points--alternative splicing of IL 4, differential receptor engagement by IL-4, and differential regulation of macrophage activation by IL-4--are summarized in light of their contributions to inflammation. PMID- 22782969 TI - Heart failure in severe aortic valve stenosis: prognostic impact of left ventricular ejection fraction and mean gradient on outcome after transcatheter aortic valve implantation. AB - AIMS: This prospective study aimed to evaluate the prognostic impact of left ventricular ejection fraction (LVEF) and aortic mean gradient patterns on outcome after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: From 2008 to 2011, 202 consecutive patients with severe symptomatic aortic valve stenosis (aortic valve area <1.0 cm(2)) were submitted to TAVI. Patients were divided into four groups according to LVEF (>50% vs. <= 50%) and aortic mean pressure gradient (>40 mmHg vs. <= 40 mmHg): group 1, preserved LVEF/high gradient (n = 86); group 2, preserved LVEF/low gradient (n = 27); group 3, reduced LVEF/high gradient (n = 45); and group 4, reduced LVEF/low gradient (n = 44). A CoreValve prosthesis (Medtronic, Minneapolis, MN, USA) was inserted retrogradely. Echocardiography was performed before and 1 year after TAVI. The primary study endpoint (1-year all-cause mortality) was reached in 47 patients (23%). All-cause mortality was lowest in group 1 (14%), intermediate in group 2 (22%) and group 3 (27%), and highest in group 4 (39%) (P = 0.007). In survivors, aortic mean gradient decreased in all patients (baseline 48 +/- 13 mmHg vs. 10 +/ 4 mmHg at 1 year, P < 0.001). LVEF improved in group 3 and group 4 (baseline 42 +/- 8% vs. 51 +/- 11% at 1 year, P < 0.001). CONCLUSION: Severe aortic stenosis with low gradient and/or reduced LVEF is associated with worse outcome after TAVI compared with aortic stenosis with preserved LVEF/high gradient. The evaluation of these haemodynamic parameters may help to improve risk stratification in patients undergoing TAVI. PMID- 22782970 TI - Prognostic importance of exercise brain natriuretic peptide in asymptomatic degenerative mitral regurgitation. AB - AIM: The exercise Doppler echocardiographic stress test can be of interest in the management of asymptomatic patients with primary mitral regurgitation (MR). The resting brain natriuretic peptide (BNP) level is a good surrogate marker of the consequences of MR and is a powerful predictor of outcome. The incremental prognostic value of BNP response during exercise is unknown. We aimed to identify the determinants of exercise BNP level and to evaluate its prognostic value in asymptomatic patients with primary MR. METHODS AND RESULTS: Comprehensive resting and exercise transthoracic Doppler echocardiography was performed in 113 consecutive asymptomatic patients with moderate to severe degenerative MR and preserved left ventricular (LV) function. Blood samples were collected both at rest and during exercise. The BNP level significantly increased from rest to exercise (P < 0.0001). The independent determinants of exercise BNP were resting E/Ea ratio (P = 0.043), indexed left atrial volume (P = 0.022), and exercise LV global longitudinal strain (P = 0.001). There was a significant graded relationship between increasing BNP level at exercise (according to tertiles) and increased incidence of cardiac events (death, heart failure, mitral valve surgery driven by symptoms, or LV dilatation/dysfunction onset) (1 year, 11 +/- 5% vs. 14 +/- 6% vs. 43.5 +/- 9%; 2 years, 21 +/- 7% vs. 40 +/- 8% vs. 67 +/- 9%; in tertiles 1, 2 and 3, respectively). On multivariable analysis, after adjustment for demographic and echocardiographic data and for resting BNP level, exercise BNP remained significantly associated with increased risk of cardiac events during the follow-up (hazard ratio 2.8 and 3.4, P = 0.041 and 0.023, for tertiles 2 and 3, as compared with tertile 1). CONCLUSIONS: In asymptomatic patients with primary MR, exercise BNP level provides incremental prognostic value beyond what is achieved by demographic and echocardiographic data and resting BNP level. Patients with elevated exercise BNP should be considered at high risk of reduced cardiac event-free survival. PMID- 22782971 TI - Minimal invasive surgery for atrial fibrillation: an updated review. AB - AIMS: Despite its proven efficacy, the Cox-Maze III procedure did not gain widespread acceptance for the treatment of stand-alone atrial fibrillation (SA AF) because of its complexity and technical difficulty. Surgical ablation for SA AF can now be successfully performed utilizing minimally invasive surgery (MIS). This study provides an overview of state-of-the-art MIS for the treatment of SA AF. METHODS AND RESULTS: Studies selected for this review were identified on PUBMED and exclusion and inclusion criteria were applied to select the publication to be screened. Twenty-eight studies were included; 27 (96.4%) were observational in nature whereas 1 was prospective non-randomized. The total number of patients was 1051 (range 14-114). Mean age ranged from 45.3 to 67.1 years. Suboptimal results were obtained when employing microwave and high focused ultrasound energies. In contrast, MIS ablation of SA-AF achieved satisfactory 1 year results when the bipolar radiofrequency was employed as energy source, with antiarrhythmic drug-free success rate comparable to percutaneous catheter ablation (PCA). The success rate in paroxysmal was even higher than in PCA. In contrast, ganglionated plexi ablation and left atrial appendage removal seem not to influence the recurrence of AF and the occurrence of postoperative thromboembolic events. CONCLUSION: Minimally invasive surgery ablation of SA-AF achieved satisfactory 1-year results when the bipolar radiofrequency was employed. Nevertheless, the relatively high complication rate reported suggest that such techniques require further refinement. Finally, the preliminary results of the hybrid approach are promising but they need to be confirmed. PMID- 22782968 TI - Relationship of serum sodium concentration to mortality in a wide spectrum of heart failure patients with preserved and with reduced ejection fraction: an individual patient data meta-analysis(?): Meta-Analysis Global Group in Chronic heart failure (MAGGIC). AB - AIMS: Hyponatraemia has been associated with reduced survival in patients with heart failure and reduced ejection fraction (HF-REF). The relationship between serum sodium and outcome is unclear in heart failure with preserved (>= 50%) ejection fraction (HF-PEF). Therefore, we used a large individual patient data meta-analysis to study the risk of death associated with hyponatraemia in HF-REF and in HF-PEF. METHODS AND RESULTS: This analysis included 14 766 patients from 22 studies that recruited patients without ejection fraction inclusion criterion at baseline and reported death from any cause. Cox proportional analysis was undertaken for hyponatraemia (sodium <135 mmol/L), adjusted for variables of clinical relevance, and stratified by study. The endpoint was death from any cause at 3 years. Patients with hyponatraemia (n = 1618) and patients with normal serum sodium had similar characteristics as regards to age, gender, and ischaemic aetiology. However, patients with hyponatraemia had higher New York Heart Association class and lower blood pressure. At follow-up, there were 335 deaths among 1618 patients with hyponatraemia (21%) and 2128 deaths among 13 148 patients with normal serum sodium (16%). The risk of death appeared to increase linearly with serum sodium levels <140 mmol/L. Hyponatraemia was identified in 1199 HF-REF patients (11%) and 419 HF-PEF patients (11%). Hyponatraemia was independently predictive of death in both HF-REF [adjusted hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.50-1.91] and HF-PEF (adjusted HR 1.40, 95% CI 1.10-1.79, P for interaction 0.20). CONCLUSION: Hyponatraemia is a powerful determinant of mortality in patients with HF regardless of ejection fraction. Further work is needed to determine if correction of hyponatraemia translates into clinical benefit. PMID- 22782972 TI - The occurrence of cardiovascular disease during 5-year follow-up in patients with idiopathic atrial fibrillation. AB - AIMS: Idiopathic atrial fibrillation (AF) may be an expression of as yet undetected underlying heart disease. We found it useful for clinical practice to study the long-term development of cardiovascular disease (CVD) in patients diagnosed with idiopathic AF. METHODS AND RESULTS: Forty-one consecutive idiopathic AF patients (56 +/- 10 years, 66% male) were compared with 45 healthy control patients in permanent sinus rhythm. Patients were free of hypertension, antihypertensive and antiarrhythmic drugs, diabetes, congestive heart failure, coronary artery or peripheral vascular disease, previous stroke, thyroid, pulmonary and renal disease, and structural abnormalities on echocardiography. Baseline characteristics and echocardiographic parameters were equal in AF cases and controls. During a mean follow-up of 66 +/- 11 months, CVD occurred significantly more often in idiopathic AF patients compared with controls (49 vs. 20%, P= 0.006). Patients with idiopathic AF were significantly younger at the time of their first CV event compared with controls (59 +/- 9 vs. 64 +/- 5 years, P= 0.027), and had more severe disease. Multivariable Cox regression analysis revealed that age, a history of AF, and echocardiographic left ventricular wall width were significant predictors of CVD development. CONCLUSION: Patients originally diagnosed with idiopathic AF develop CVD more often, at younger age, and with a more severe disease profile compared with healthy sinus rhythm control patients. The detection and treatment of CVD in an early stage could improve the prognosis of these patients. At present it seems prudent to regularly check idiopathic AF patients for the insidious development of CVD. PMID- 22782973 TI - Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids. AB - Mitochondrial enoyl-CoA isomerase (ECI1) is an auxiliary enzyme involved in unsaturated fatty acid oxidation. In contrast to most of the other enzymes involved in fatty acid oxidation, a deficiency of ECI1 has yet to be identified in humans. We used wild-type (WT) and Eci1-deficient knockout (KO) mice to explore a potential presentation of human ECI1 deficiency. Upon food withdrawal, Eci1-deficient mice displayed normal blood beta-hydroxybutyrate levels (WT 1.09 mM vs. KO 1.10 mM), a trend to lower blood glucose levels (WT 4.58 mM vs. KO 3.87 mM, P=0.09) and elevated blood levels of unsaturated acylcarnitines, in particular C12:1 acylcarnitine (WT 0.03 MUM vs. KO 0.09 MUM, P<0.01). Feeding an olive oil-rich diet induced an even greater increase in C12:1 acylcarnitine levels (WT 0.01 MUM vs. KO 0.04 MUM, P<0.01). Overall, the phenotypic presentation of Eci1-deficient mice is mild, possibly caused by the presence of a second enoyl-CoA isomerase (Eci2) in mitochondria. Knockdown of Eci2 in Eci1 deficient fibroblasts caused a more pronounced accumulation of C12:1 acylcarnitine on incubation with unsaturated fatty acids (12-fold, P<0.05). We conclude that Eci2 compensates for Eci1 deficiency explaining the mild phenotype of Eci1-deficient mice. Hypoglycemia and accumulation of C12:1 acylcarnitine might be diagnostic markers to identify ECI1 deficiency in humans. PMID- 22782975 TI - Supplementation of fibrinogen in acquired bleeding disorders: experience, evidence, guidelines, and licences. PMID- 22782976 TI - Ketamine as an adjunct to caudal block in neonates and infants: is it time to re evaluate? PMID- 22782974 TI - Promoter methylation confers kidney-specific expression of the Klotho gene. AB - The aging suppressor geneKlotho is predominantly expressed in the kidney irrespective of species. Because Klotho protein is an essential component of an endocrine axis that regulates renal phosphate handling, the kidney-specific expression is biologically relevant; however, little is known about its underlying mechanisms. Here we provide in vitro and in vivo evidence indicating that promoter methylation restricts the expression of the Klotho gene in the kidney. Based on evolutionary conservation and histone methylation patterns, the region up to -1200 bp was defined as a major promoter element of the human Klotho gene. This region displayed promoter activity equally in Klotho-expressing and nonexpressing cells in transient reporter assays, but the activity was reduced to ~20% when the constructs were integrated into the chromatin in the latter. Both endogenous and transfected Klotho promoters were 30-40% methylated in Klotho nonexpressing cells, but unmethylated in Klotho-expressing renal tubular cells. DNA demethylating agents increased Klotho expression 1.5- to 3.0-fold in nonexpressing cells and restored the activity of silenced reporter constructs. Finally, we demonstrated that a severe hypomorphic allele of Klotho had aberrant CpG methylation in kl/kl mice. These findings might be useful in therapeutic intervention for accelerated aging and several complications caused by Klotho down-regulation. PMID- 22782977 TI - Cancer biology, analgesics, and anaesthetics: is there a link? PMID- 22782978 TI - Status of national guidelines in dictating individual clinical practice and defining negligence: letter 1. PMID- 22782979 TI - Status of national guidelines in dictating individual clinical practice and defining negligence: letter 2. PMID- 22782981 TI - Tracheal intubation in the critically ill: just say no to drugs. PMID- 22782983 TI - Epidural blood patch is the gold standard treatment for dural puncture headache. PMID- 22782985 TI - Ultrasound-assisted spinal anaesthesia in a patient with Wildervanck syndrome and congenital abnormalities of the lumbar spine. PMID- 22782986 TI - Outcomes and patterns of infections in patients with underlying haematological malignancies admitted to intensive care. PMID- 22782987 TI - Protracted cerebral circulatory arrest and cortical electrical silence coexisting with preserved respiratory drive and flexor motor response. PMID- 22782988 TI - Bladder control increases the incidence of urinary retention after epidural analgesia after paediatric orthopaedic surgery. PMID- 22782989 TI - Harlequin syndrome after extrapleural bupivacaine infusion. PMID- 22782994 TI - Effect of sustained inflation duration; resuscitation of near-term asphyxiated lambs. AB - OBJECTIVE: The 2010 ILCOR neonatal resuscitation guidelines do not specify appropriate inflation times for the initial lung inflations in apnoeic newborn infants. The authors compared three ventilation strategies immediately after delivery in asphyxiated newborn lambs. DESIGN: Experimental animal study. SETTING: Facility for animal research. SUBJECTS: Eighteen near-term lambs (weight 3.5-3.9 kg) delivered by caesarean section. INTERVENTIONS: Asphyxia was induced by occluding the umbilical cord and delaying ventilation onset (10-11 min) until mean carotid blood pressure (CBP) was <=22 mm Hg. Animals were divided into three groups (n=6) and ventilation started with: (1) inflation times of 0.5 s at a ventilation rate 60/min, (2) five 3 s inflations or (3) a single 30 s inflation. Subsequent ventilation used inflations at 0.5 s at 60/min for all groups. MAIN OUTCOME MEASURES: Times to reach a heart rate (HR) of 120 bpm and a mean CBP of 40 mm Hg. Secondary outcome was change in lung compliance. RESULTS: Median time to reach HR 120 bpm and mean CBP 40 mm Hg was significantly shorter in the single 30 s inflation group (8 s and 74 s) versus the 5*3 s inflation group (38 s and 466 s) and the conventional ventilation group (64 s and 264 s). Lung compliance was significantly better in the single 30 s inflation group. CONCLUSION: A single sustained inflation of 30 s immediately after birth improved speed of circulatory recovery and lung compliance in near-term asphyxiated lambs. This approach for neonatal resuscitation merits further investigation. PMID- 22782995 TI - Treatment of presumed hypotension in very low birthweight neonates: effects on regional cerebral oxygenation. AB - CONTEXT: Previous studies have correlated poor neurological outcomes with hypotension. Treatment of hypotension in very low birthweight (VLBW) infants is common, and most often is based solely on the blood pressure measurement. Whether treatment improves cerebral oxygenation is unclear. OBJECTIVE: To determine if treatment of hypotension in VLBW neonates results in an increase in cerebral oxygenation. PATIENTS AND METHODS: In this single centre observational study, neonates <30 weeks and <1500 grams, blood pressure and regional cerebral oximetry (rCSO2) with near infrared spectroscopy were continuously monitored and digitally recorded. If patients were treated for hypotension during the first 3 days of life, effects of treatment on blood pressure and regional cerebral saturation were determined. RESULTS: Twenty-eight of 50 patients were treated by the medical team for hypotension, of which 22 had accurate data recorded for analysis. Both normal saline 10 ml/kg, and dopamine 2.5-5 mcg/kg per min significantly increased blood pressure, (saline 26.8+/-3.5 to 28.8+/-4.2 mm Hg, p<0.005; dopamine 27.6+/ 1.9 to 29.5+/-3.2 mm Hg, p<0.02). Pre-treatment values of rCSO2 were similar to published normative values and treatment with either normal saline or dopamine had no effect on rCSO2. CONCLUSION: These results suggest that treating hypotension in VLBW neonates based solely on a blood pressure measurement of less than 30 mm Hg, while increasing blood pressure, may not increase cerebral oxygenation, possibly because many of these patients are in the autoregulatory zone for cerebral blood flow. PMID- 22782997 TI - Ankylosing spondylitis with cervical fracture, cardiac arrest, locked-in syndrome and death. PMID- 22782996 TI - Proteomic and pathway analyses reveal a network of inflammatory genes associated with differences in skin tumor promotion susceptibility in DBA/2 and C57BL/6 mice. AB - Genetic susceptibility to two-stage skin carcinogenesis is known to vary significantly among different stocks and strains of mice. In an effort to identify specific protein changes or altered signaling pathways associated with skin tumor promotion susceptibility, a proteomic approach was used to examine and identify proteins that were differentially expressed in epidermis between promotion-sensitive DBA/2 and promotion-resistant C57BL/6 mice following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). We identified 19 differentially expressed proteins of which 5 were the calcium-binding proteins annexin A1, parvalbumin alpha, S100A8, S100A9, and S100A11. Further analyses revealed that S100A8 and S100A9 protein levels were also similarly differentially upregulated in epidermis of DBA/2 versus C57BL/6 mice following topical treatment with two other skin tumor promoters, okadaic acid and chrysarobin. Pathway analysis of all 19 identified proteins from the present study suggested that these proteins were components of several networks that included inflammation associated proteins known to be involved in skin tumor promotion (e.g. TNF-alpha, NFkappaB). Follow-up studies revealed that Tnf, Nfkb1, Il22, Il1b, Cxcl1, Cxcl2 and Cxcl5 mRNAs were highly expressed in epidermis of DBA/2 compared with C57BL/6 mice at 24h following treatment with TPA. Furthermore, NFkappaB (p65) was also highly activated at the same time point (as measured by phosphorylation at ser276) in epidermis of DBA/2 mice compared with C57BL/6 mice. Taken together, the present data suggest that differential expression of genes involved in inflammatory pathways in epidermis may play a key role in genetic differences in susceptibility to skin tumor promotion in DBA/2 and C57BL/6 mice. PMID- 22782998 TI - Isolated ileal bezoar causing small bowel obstruction. AB - Bezoars are a mass of ingested foreign materials commonly found in stomach in patients with psychiatric problems or history of gastric surgery. Bezoars are classified based on their composition. Frequently encountered are trichobezoars and phytobezoars composed of hair and fibres of fruits and vegetables, respectively. Primary small-bowel bezoars are a rarity and are essentially encountered in patients having small-bowel diseases such as diverticuli, strictures or tumours. Ileal bezoar leading to intestinal obstruction in absence of parent bezoar in stomach is very rare and so we present a case report here. The diagnosis was made on CT scan in which the cause was found to be an ileal bezoar. Surgical resection of the involved segment was performed and diagnosis confirmed on histopathological examination. PMID- 22782999 TI - FNAC site metastasis in gall bladder cancer--a rare presentation. AB - Gall bladder malignancy is very common in northern part of India. The diseases can virtually metastasise to every organ of the body however; skin metastasis from gall bladder cancer is extremely rare. The authors report, probably the first case of fine needle aspiration cytology site metastasis on anterior abdominal wall skin from adenocarcinoma of the gall bladder. PMID- 22783000 TI - A very high amylase can be benign in paediatric Crohn's disease. AB - A 12.5-year-old boy with Crohn's disease with abdominal pain had a raised amylase of 1835 IU/l with normal lipase levels. Ultrasound showed no evidence of inflammation of pancreas. The amylase to creatinine clearance ratio, was 0.8% (reference interval 2%-5%; >6% consistent with acute pancreatitis; <1.6% with macroamylasemia), suggesting he had raised serum amylase with a corresponding reduced clearance of amylase in his urine, positively supporting the diagnosis of macroamylasemia. Macroamylasemia has no clinical significance other than misdiagnosis as acute pancreatitis. Awareness of this condition is important and a positive diagnosis should always be made to avoid unnecessary changes in treatments. PMID- 22783001 TI - Brake fluid toxicity feigning brain death. AB - Brake fluid (glycol-based) toxicity is known to have a protean of central and peripheral nervous system manifestations. The principal component of this household poison is ethylene glycol. Toxic effect is generally attributed to peri vascular deposition of calcium oxalate crystals in various tissues. However, clinical features resembling brain death have rarely been reported. We report a case of brake fluid toxicity simulating brain death in a 21-year-old healthy man who ingested it as a recreational agent. PMID- 22783002 TI - A minor lid laceration concealing a potentially life-threatening injury. AB - A 29-year-man presented with an injury to his left upper lid, having stumbled onto the tip of a pool cue. He presented with minimal signs and symptoms, initially thought as a minor lid laceration and was managed with lid suturing. Two months later, he presented with vertical diplopia on upward gaze and showed a picture consistent with traumatic Brown's syndrome. Subsequent imaging revealed the extent of orbital injury and confirmed a retained foreign body embedded in the frontal lobe of the brain. This was surgically removed and found to represent the tip of the pool cue. Postoperatively, the patient made a good recovery, although he still has a slight residual diplopia on upward gaze. PMID- 22783003 TI - Gastrointestinal stromal tumour originating from the hepatic falciform ligament. AB - Primary extraluminal gastrointestinal stromal tumours (GISTs) originating from outside of the GI tract are not uncommon. However, none have been reported to arise from the falciform ligament of the liver. The natural history and prognostic indicators for primary GISTs, while still unclear, have been under much investigation, and some promising therapeutic options have surfaced, including surgical removal and adjuvant chemotherapy with imatinib. PMID- 22783004 TI - Oral ranula in an HIV-positive patient: case report and literature review. AB - We describe the presentation and treatment of an HIV-positive patient with an oral ranula, and review the literature. Ranulas are mucoceles or retention cysts formed by the extravasation of mucus from the sublingual gland, presumably due to continued production of saliva in the presence of ductal obstruction. Oral ranulas in children are rare and the overall prevalence of mucoceles has been reported as 0.08% in children aged 0-12 years. However, there has been a documented increased occurrence in HIV-positive patients. This has been attributed to a blockage of the salivary gland by inflammation and peri-ductal fibrosis following HIV-associated salivary gland disease. Oral lesions may indicate infection with HIV and can also predict progression of HIV to AIDS. The most common oral manifestation is oral candidiasis occurring in 67% of children with HIV. Following this salivary gland disease, periodontal and gingival disease and herpes simplex are the next most common. The exact prevalence of ranulas in an HIV population is not known but the occurrence of a paediatric patient with HIV having at least one oral lesion has been documented as high as 63% and salivary gland disease at 50%. The true extent of the relationship between HIV and ranula is as yet unknown. This represents the only reported case of oral ranula in an HIV-positive patient in the UK. PMID- 22783005 TI - Acute onset quadriplegia. AB - A 50-year-old man, with history of chronic alcohol intake was brought in a stuporous state to the emergency services having been found in that condition in his home the same day. Examination revealed the patient in an akinteic mute state with apparently normal cranial nerves, hypotonia and quadriplegia with bilateral extensor plantar reflex. CT scan and MRI of the brain revealed bilateral infarct parasagittally with normal Magnetic resonance venogram suggestive of bilateral anterior cerebral artery infarct. Follow-up magnetic resonance angiogram revealed an azygous anterior cerebral artery thus proving an infarct of unpaired anterior cerebral artery infarct as the cause for quadriplegia in this patient. PMID- 22783006 TI - Abnormal gas pattern under diaphragm. PMID- 22783007 TI - Polyneuropathy: a poetic diagnosis. AB - A 60-year-old woman presented with subacute progressive lower extremity weakness. This was associated with a 40lb weight loss and fevers. She was previously healthy, aside from renal transplantation 9 years earlier for end stage renal disease resulting from IgA nephropathy. On examination, she had clubbing, a single lymph node in the right cervical chain, and objective findings of lower extremity weakness with lower motor neuron findings. Investigations revealed a thrombocytosis and elevated CSF protein. Electromyographic evidence of diffuse polyradiculopathy with demyelination was documented. On imaging, she had a large lytic/sclerotic lesion in the right scapula measuring 8 cm, a pericardial effusion, and borderline splenomegaly. Pathological assessment of the excised lymph node revealed Castleman-like changes; biopsy of the right scapular lesion revealed lambda-restricted plasma cells, in the absence of a monoclonal protein in the bone marrow or periphery. A diagnosis of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) with plasmacytoma was established; a post-transplant lymphoproliferative disorder was suspected. PMID- 22783008 TI - Calcium pyrophosphate dihydrate deposition in the trochanteric hip bursa presenting as acute hip pain. AB - Acute hip pain is a common reason for attendance to hospital. Immediate diagnoses include occult fractures, infectious and non-infectious inflammatory processes such as gout and pseudogout. Calcium pyrophosphate deposition disease (CPDD) is a rheumatological syndrome affecting articular cartilage and/or synovial fluid. It can occur as a clinical presentation (pseudogout) where calcium pyrophosphate dihydrate (CPPD) crystals are deposited within the joint space or radiographically, as chondrocalcinosis (CC), where CPPD crystals are deposited onto articular cartilages. Extraarticular manifestations of CPDD are rare. The authors report a case of CPPD deposition in the trochanteric bursa of a 35-year old woman presenting as acute hip pain. The patient was treated successfully during arthroscopy with removal of the deposits and excision of the bursa. The patient remains well at 6 month follow-up. PMID- 22783009 TI - Bilateral common carotid artery dissection. AB - A 63-year-old Japanese man with no significant medical or family history was admitted for sudden consciousness disturbance, left hemiparesis and shock. Physical examination showed internal carotid artery asymmetry on palpation and significant differential blood pressure in both upper arms. A thoracic CT scan showed classic aortic dissection from the ascending aorta through the common iliac artery, classic dissection of the left common carotid artery and an intramural haematoma in the right common carotid artery. The patient's consciousness level gradually improved, and he underwent emergency surgery involving aortic rebuilding with a synthetic graft. Subsequently, he had a good clinical course. PMID- 22783010 TI - Apical hypertrophic cardiomyopathy in an Indian patient: straight from the book. PMID- 22783011 TI - High-output heart failure in a newborn. AB - High-output cardiac failure is rare in newborns. Emergent diagnosis and management of this pathology is crucial. We report the case of a child, currently 12-months old; obstetric background is non-contributory. Clinic observation on D1 was normal except for the presence of a systolic cardiac murmur; cardiological evaluation revealed mild ventricular dysfunction of the right ventricle. On the third day of life, she developed cardiac failure with gallop rhythm, hepatomegaly and a murmur in the anterior fontanel; an echocardiogram confirmed clinic aggravation with biventricular dysfunction and right cavities and superior vena cava dilatation. The cranial MRI confirmed the presence of a pial arteriovenous malformation (AVM) involving the anterior and middle cerebral arteries with an associated fronto-parietal ischaemic lesion. The infant underwent embolisations of AVM with successful flow reduction and cardiac failure improvement. The multidisciplinary follow-up showed no cardiac dysfunction or permanent lesions but confirmed a severe psycho-motor delay and left hemiparesia. PMID- 22783012 TI - Atypical presentation of Boerhaave's syndrome. AB - Boerhaave's syndrome is the rare and often fatal condition of spontaneous oesophageal rupture. When present with atypical symptoms, diagnosis is frequently late, which contributes to the high morbidity and mortality. The authors describe a unique case of a 50-year-old man presented with atypical Boerhaave's syndrome, in which the diagnosis was made several days following presentation by observing a large pleural effusion that had evolved rapidly on chest radiographs. He was managed without thoracotomy. Although survival has been reported with non operative management of contained oesophageal perforations, to our knowledge, this is the rare case report of surviving Boerhaave's syndrome with free pleural rupture, without thoracotomy. PMID- 22783013 TI - A spontaneous coronary arterial dissection associated with a calcineurin inhibitor. AB - We present the case of a 55-year-old lady presenting 5 months after a liver transplant with acute coronary syndrome. She was on maintenance-dose tacrolimus. An angiogram diagnosed a spontaneous coronary artery dissection, which was successfully stented. This is the third case in the literature associating a calcineurin inhibitor with a spontaneous coronary arterial dissection. The detrimental effect of calcineurin inhibitors on vasculature is well recognised. This report highlights their potentially serious side-effects. It should be appreciated that calcineurin inhibitors have the potential to cause or contribute to this rare vascular phenomenon and the diagnosis should therefore be considered in those taking such drugs. PMID- 22783014 TI - Interferon regulatory factor 8 integrates T-cell receptor and cytokine-signaling pathways and drives effector differentiation of CD8 T cells. AB - We recently demonstrated that differentiation of cytotoxic T cells requires cooperation between T-cell receptor (TCR)/costimulation and gammac-cytokines. Here we demonstrate that the transcription factor IFN regulatory factor 8 (IRF8) is expressed in CD8 T cells by the combination of these two signals. More importantly, depletion of IRF8 in these cells abrogated the differentiation of naive CD8 T cells into effector cells in an experimental graft-vs.-host disease mouse model. We also show that IRF8 seems to not operate upstream of other critical factors such as T-bet and eomesodermin, which have been implicated in effector maturation. Collectively, our work shows that IRF8 integrates the TCR/costimulation and gammac-cytokine-signaling pathways and mediates the transition of naive CD8 T cells to effector cells, thus identifying IRF8 as one of the molecular regulators of CD8 T-cell differentiation. PMID- 22783015 TI - Modeling huanglongbing transmission within a citrus tree. AB - The citrus disease huanglongbing (HLB), associated with an uncultured bacterial pathogen, is threatening the citrus industry worldwide. A mathematical model of the transmission of HLB between its psyllid vector and citrus host has been developed to characterize the dynamics of the vector and disease development, focusing on the spread of the pathogen from flush to flush (a newly developing cluster of very young leaves on the expanding terminal end of a shoot) within a tree. This approach differs from that of prior models for vector-transmitted plant diseases where the entire plant is the unit of analysis. Dynamics of vector and host populations are simulated realistically as the flush population approaches complete infection. Model analysis indicates that vector activity is essential for initial infection but is not necessary for continued infection because infection can occur from flush to flush through internal movement in the tree. Flush production, within-tree spread, and latent period are the most important parameters influencing HLB development. The model shows that the effect of spraying of psyllids depends on time of initial spraying, frequency, and efficacy of the insecticides. Similarly, effects of removal of symptomatic flush depend on the frequency of removal and the time of initiation of this practice since the start of the epidemic. Within-tree resistance to spread, possibly affected by inherent or induced resistance, is a major factor affecting epidemic development, supporting the notion that alternate routes of transmission besides that by the vector can be important for epidemic development. PMID- 22783018 TI - Effects of a single nucleotide polymorphism in the chicken NK-lysin gene on antimicrobial activity and cytotoxicity of cancer cells. AB - NK-lysin is an effector protein of the innate immune system and an important component of host protection. We isolated a SNP in the NK-lysin coding sequence among different chicken breeds. This A to G substitution at the position 271 nucleotide in the ORF results in an Asn (N) to Asp (D) amino acid alteration. We synthesized two 30-aa peptides (N29N and N29D) to compare the biological activity of the helix 2-loop-helix 3 region of NK-lysin resulting from the polymorphic gene. Both peptides were found to be cytotoxic in bacteria and tumor cell cultures at micromolar concentrations. The N29N peptide, however, exhibited greater antibacterial and anticancer activity than the N29D peptide. Circular dichroism spectroscopy of the two peptides in negatively charged single unilamellar vesicles showed spectra typical of alpha-helical peptides. The helical profile of N29D was reduced substantially compared with that of N29N. However, no structural change was observed in neutral vesicles. zeta-Potential measurements of liposomes incubated with increasing peptide concentrations allowed surface charge neutralization with a negatively charged lipid, but not with a zwitterionic lipid. This result suggests that a difference in electrostatic interaction between lipid membranes and the helical peptides results from the polymorphic gene and is subsequently an important factor in cell lytic activity of variant NK-lysin peptides. PMID- 22783020 TI - Tmem100, an ALK1 receptor signaling-dependent gene essential for arterial endothelium differentiation and vascular morphogenesis. AB - Members of the transforming growth factor-beta superfamily play essential roles in various aspects of embryonic development and physiological organ function. Among them, bone morphogenetic protein (BMP) 9 and BMP10 regulate embryonic vascular development by activating their endothelial receptor ALK1 (activin receptor-like kinase 1, also called Acvrl1). ALK1-mediated intracellular signaling is implicated in the etiologies of human diseases, but their downstream functional proteins are largely unknown. In this study, we identified Tmem100, a gene encoding a previously uncharacterized intracellular transmembrane protein, to be an embryonic endothelium-enriched gene activated by BMP9 and BMP10 through the ALK1 receptor. Tmem100 null mice showed embryonic lethality due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis, which phenocopied most of the vascular abnormalities observed with the Acvrl1/Alk1 deficiency. The activity of Notch- and Akt-mediated signaling, which is essential for vascular development, was down-regulated in Tmem100 null mice. Cre-mediated deletion of Tmem100 in endothelial cells was sufficient to recapitulate the null phenotypes. These data indicated that TMEM100 may play indispensable roles downstream of BMP9/BMP10-ALK1 signaling during endothelial differentiation and vascular morphogenesis. PMID- 22783021 TI - Unobserved time effects confound the identification of climate change impacts. AB - A recent study by Feng et al. [Feng S, Krueger A, Oppenheimer M (2010) Proc Natl Acad Sci USA 107:14257-14262] in PNAS reported statistical evidence of a weather driven causal effect of crop yields on human migration from Mexico to the United States. We show that this conclusion is based on a different statistical model than the one stated in the paper. When we correct for this mistake, there is no evidence of a causal link. PMID- 22783022 TI - The Sin3a repressor complex is a master regulator of STAT transcriptional activity. AB - Tyrosine phosphorylation is a hallmark for activation of STAT proteins, but their transcriptional activity also depends on other secondary modifications. Type I IFNs can activate both the ISGF3 (STAT1:STAT2:IRF9) complex and STAT3, but with cell-specific, selective triggering of only the ISGF3 transcriptional program. Following a genome-wide RNAi screen, we identified the SIN3 transcription regulator homolog A (Sin3a) as an important mediator of this STAT3-targeted transcriptional repression. Sin3a directly interacts with STAT3 and promotes its deacetylation. SIN3A silencing results in a prolonged nuclear retention of activated STAT3 and enhances its recruitment to the SOCS3 promoter, concomitant with histone hyperacetylation and enhanced STAT3-dependent transcription. Conversely, Sin3a is required for ISGF3-dependent gene transcription and for an efficient IFN-mediated antiviral protection against influenza A and hepatitis C viruses. The Sin3a complex therefore acts as a context-dependent ISGF3/STAT3 transcriptional switch. PMID- 22783024 TI - Glycated haemoglobin A1c and diagnosis of diabetes. The test has finally come of age. PMID- 22783025 TI - Diuretics: a review. AB - Diuretics, in one form or another, have been around for centuries and this review sets out to chart their development and clinical use. Starting with the physiology of the kidney, it progresses to explain how diuretics actually work, via symports on the inside of the renal tubules. The different classes of diuretics are characterized, along with their mode of action. The clinical use of diuretics in conditions like congestive cardiac failure and hypertension, as well as some rarer, but clinically important, conditions is then examined. An account is given of the adverse effects of diuretics and how they come about. Common adverse effects like hypokalaemia and hyponatraemia are examined in some detail, and other electrolyte disturbances like hypomagnesaemia also gain a mention. Diuretic use in chronic kidney disease is examined and new guidelines that have been introduced are presented. A section on diuretic abuse is included as this is becoming an all too common clinical scenario, and the sometimes tragic consequences of this abuse are emphasized. Diuretics also find a role in the diagnosis of forms of renal tubular acidosis and this role is explored. Finally, a selection of some of the newer approaches to diuretic therapy are presented, often the consequence of the increasing development of molecular biology, and some of the novel compounds - which may be in drug formularies of the future - are revealed. PMID- 22783026 TI - Non-classical congenital adrenal hyperplasia in association with porphyria cutanea tarda: co-incidence or trigger? AB - We present an interesting case of porphria cutanea tarda with hereditary haemochromatosis and non-classical congenital adrenal hyperplasia in a postmenopausal woman. This unusual combination of conditions does not appear to be reported in the literature. The exact mechanism causing porphyria in this patient is not clear. We consider the possibility that in addition to iron accumulation and excess alcohol, altered steroid milieu may have been a possible trigger for the development of bullous lesions in this patient. PMID- 22783023 TI - Synapse type-independent degradation of the endocannabinoid 2 arachidonoylglycerol after retrograde synaptic suppression. AB - The endocannabinoid 2-arachidonoylglycerol (2-AG) mediates retrograde synaptic suppression. Although the mechanisms of 2-AG production are well characterized, how 2-AG is degraded is less clearly understood. Here we found that expression of the 2-AG hydrolyzing enzyme monoacylglycerol lipase (MGL) was highly heterogeneous in the cerebellum, being rich within parallel fiber (PF) terminals, weak in Bergman glia (BG), and absent in other synaptic terminals. Despite this highly selective MGL expression pattern, 2-AG-mediated retrograde suppression was significantly prolonged at not only PF-Purkinje cell (PC) synapses but also climbing fiber-PC synapses in granule cell-specific MGL knockout (MGL-KO) mice whose cerebellar MGL expression was confined to the BG. Virus-mediated expression of MGL into the BG of global MGL-KO mice significantly shortened 2-AG-mediated retrograde suppression at PF-PC synapses. Furthermore, contribution of MGL to termination of 2-AG signaling depended on the distance from MGL-rich PFs to inhibitory synaptic terminals. Thus, 2-AG is degraded in a synapse-type independent manner by MGL present in PFs and the BG. The results of the present study strongly suggest that MGL regulates 2-AG signaling rather broadly within a certain range of neural tissue, although MGL expression is heterogeneous and limited to a subset of nerve terminals and astrocytes. PMID- 22783027 TI - Drug shortages: what can hospital pharmacists do? PMID- 22783028 TI - Development and validation of a novel vancomycin dosing nomogram for achieving high-target trough levels at 2 canadian teaching hospitals. AB - BACKGROUND: Recent guidelines recommend a vancomycin trough (predose) level between 15 and 20 mg/L in the treatment of invasive gram-positive infections, but most initial dosing nomograms are designed to achieve lower targets (5-15 mg/L). Clinicians need guidance about appropriate initial dosing to achieve the higher target. OBJECTIVE: To develop and validate a high-target vancomycin dosing nomogram to achieve trough levels of 15-20 mg/L. METHODS: A retrospective study was conducted at 2 teaching hospitals, St Paul's Hospital and Vancouver General Hospital in Vancouver, British Columbia. Patients who were treated with vancomycin between January 2008 and June 2010 and who had achieved a trough level of 14.5-20.5 mg/L were identified. Demographic and clinical data were collected. Multiple linear regression was used to develop a vancomycin dosing nomogram for each hospital site. An integrated nomogram was constructed by merging the data from the 2 hospitals. A unique set of patients at each institution was used for validating their respective nomograms and a pooled group of patients for validating the integrated nomogram. Predictive success was evaluated, and a nomogram was deemed significantly different from another nomogram if p < 0.05 via "chi(2) testing. RESULTS: Data from 78 patients at one hospital and 91 patients at the other were used in developing the respective institutional nomograms. For each hospital's data set, both age and initial serum creatinine were significantly associated with the predicted dosing interval (p < 0.001). Validation in a total of 105 test patients showed that the integrated nomogram had a predictive success rate of 56%. CONCLUSIONS: A novel vancomycin dosing nomogram was developed and validated at 2 Canadian teaching hospitals. This integrated nomogram is a tool that clinicians can use in selecting appropriate initial vancomycin regimens on the basis of age and serum creatinine, to achieve high-target levels of 15-20 mg/L. The nomogram should not replace clinical judgment for patients with unstable and/or reduced renal function. PMID- 22783029 TI - Presence and accuracy of drug dosage recommendations for continuous renal replacement therapy in tertiary drug information references. AB - BACKGROUND: Clinicians commonly rely on tertiary drug information references to guide drug dosages for patients who are receiving continuous renal replacement therapy (CRRT). It is unknown whether the dosage recommendations in these frequently used references reflect the most current evidence. OBJECTIVE: To determine the presence and accuracy of drug dosage recommendations for patients undergoing CRRT in 4 drug information references. METHODS: Medications commonly prescribed during CRRT were identified from an institutional medication inventory database, and evidence-based dosage recommendations for this setting were developed from the primary and secondary literature. The American Hospital Formulary System-Drug Information (AHFS-DI), Micromedex 2.0 (specifically the DRUGDEX and Martindale databases), and the 5th edition of Drug Prescribing in Renal Failure (DPRF5) were assessed for the presence of drug dosage recommendations in the CRRT setting. The dosage recommendations in these tertiary references were compared with the recommendations derived from the primary and secondary literature to determine concordance. RESULTS: Evidence-based drug dosage recommendations were developed for 33 medications administered in patients undergoing CRRT. The AHFS-DI provided no dosage recommendations specific to CRRT, whereas the DPRF5 provided recommendations for 27 (82%) of the medications and the Micromedex 2.0 application for 20 (61%) (13 [39%] in the DRUGDEX database and 16 [48%] in the Martindale database, with 9 medications covered by both). The dosage recommendations were in concordance with evidence-based recommendations for 12 (92%) of the 13 medications in the DRUGDEX database, 26 (96%) of the 27 in the DPRF5, and all 16 (100%) of those in the Martindale database. CONCLUSIONS: One prominent tertiary drug information resource provided no drug dosage recommendations for patients undergoing CRRT. However, 2 of the databases in an Internet-based medical information application and the latest edition of a renal specialty drug information resource provided recommendations for a majority of the medications investigated. Most dosage recommendations were similar to those derived from the primary and secondary literature. The most recent edition of the DPRF is the preferred source of information when prescribing dosage regimens for patients receiving CRRT. PMID- 22783030 TI - Vomiting of oral medications by pediatric patients: survey of medication redosing practices. AB - BACKGROUND: At the time of this study, the authors' pediatric tertiary care hospital had no policy to guide actions when a child vomited after ingesting oral medication, and limited information was available in the literature. OBJECTIVES: To characterize this clinical problem at the study hospital, to identify current practices related to redosing of medications at the study hospital, and to collect guidelines and opinions of health care professionals at other pediatric hospitals on this topic. METHODS: Two online surveys were conducted, each over a 1-month period in late 2010, to identify current practices and opinions of pediatric health care professionals about redosing of medications after vomiting. E-mail distribution lists and health care forums were used to recruit participants. RESULTS: Of the 76 responses from the study hospital, 65 were suitable for analysis. Many respondents reported encountering vomiting after administration of oral medications on a weekly (25 [38%]) or monthly (24 [37%]) basis. Most of the respondents reported that they would follow a general rule to redose if vomiting occurred within 30 min (39 [60%]) or 15 min (21 [32%]) after initial ingestion. When respondents were asked to rate the importance of 8 factors potentially affecting the decision to redose, more than half indicated that time after dose ingestion (59 [91%]), medication type (45 [69%]), patient status (39 [60%]), and visibility of medication in the vomitus (36 [55%]) were very important. Of the 53 respondents to the survey of health care professionals at other institutions, 16 (30%) indicated that their pediatric hospital or ward had a guideline on redosing in cases of vomiting after administration of oral medications. Most respondents (12/13 [92%]) stated that the guideline took into account the interval between initial ingestion and vomiting. CONCLUSIONS: The problem of vomiting after administration of an oral medication was prevalent at the study hospital, and guidelines were scarce at other pediatric institutions. Health care professionals at the study hospital and other institutions listed the time between ingestion and vomiting as the most important factor in the decision to redose the medication. PMID- 22783031 TI - A needs assessment study of hospital pharmacy residency preceptors. AB - BACKGROUND: Canadian pharmacy residency programs rely on preceptors to support the growing demand of graduates wishing to pursue hospital residencies. Understanding the educational needs of these preceptors is important to ensure that they are well prepared to deliver successful programs. OBJECTIVE: To determine what new and experienced residency preceptors self-identify as learning needs in order to become more effective preceptors for pharmacy residents. METHODS: A needs assessment of preceptors from the 31 accredited Canadian general hospital pharmacy residency programs was conducted. The study had 4 key components: interviews and focus group discussions with key informants, a pilot study, an online survey, and member checking (seeking clarification and further explanation from study participants). The residency coordinators and a convenience sample of 5 preceptors from each program were invited to participate in the survey component. RESULTS: Of a possible 186 participants, 132 (71%) responded to the survey. Of these, 128 (97%) were confident that they met the 2010 standards of the Canadian Hospital Pharmacy Residency Board (CHPRB). Preceptors ranked communication skills, giving effective feedback, and clinical knowledge as the most important elements of being an effective preceptor. Managing workload, performing evaluations, and dealing with difficult residents were commonly reported challenges. Preceptors expressed a preference for interactive workshops and mentorship programs with experienced colleagues when first becoming preceptors, followed by 1-day training sessions or online learning modules every other year for ongoing educational support. The most beneficial support topics selected were providing constructive feedback, practical assessment strategies, small-group teaching strategies, effective communication skills, and setting goals and objectives. CONCLUSIONS: This study identified several learning needs of hospital residency preceptors and showed that preceptors would appreciate educational support. Utilization of these results by residency program administrators, the CHPRB, and faculties of pharmacy could be beneficial for residency programs across Canada. PMID- 22783032 TI - Tigecycline treatment of urinary tract infection and prostatitis: case report and literature review. PMID- 22783034 TI - Development and implementation of a regional program for the safe handling of hazardous drugs by hospital pharmacies. PMID- 22783033 TI - [Not Available]. PMID- 22783035 TI - Practice spotlight: volunteer pharmacists in sub-saharan Africa. PMID- 22783036 TI - Should all pharmacists responsible for pharmacotherapeutic management of patients with complex or special drug therapy needs have certification from the board of pharmacy specialties? PMID- 22783037 TI - [Not Available]. PMID- 22783038 TI - [Not Available]. PMID- 22783039 TI - Viewing Pharmacy through a Public Health Lens. PMID- 22783040 TI - The Impact of Early Interpersonal Experience on Adult Romantic Relationship Functioning: Recent Findings from the Minnesota Longitudinal Study of Risk and Adaptation. AB - Adopting an organizational view on social development, we have investigated how interpersonal experiences early in life prospectively predict how well individuals resolve relationship conflicts, recover from conflicts, and have stable, satisfying relationships with their romantic partners in early adulthood. We have also identified specific intervening interpersonal experiences during middle childhood and adolescence that mediate the connection between how individuals regulated their emotions with their parents very early in life and as young adults in their romantic relationships. We discuss the many advantages of adopting an organizational view on social development. PMID- 22783041 TI - Ghrelin's second life: from appetite stimulator to glucose regulator. AB - Ghrelin, a 28 amino acid peptide hormone produced by the stomach, was the first orexigenic hormone to be discovered from the periphery. The octanoyl modification at Ser3, mediated by ghrelin O-acyltransferase (GOAT), is essential for ghrelin's biological activity. Ghrelin stimulates food intake through binding to its receptor (GRLN-R) on neurons in the arcuate nucleus of the hypothalamus. Ghrelin is widely expressed throughout the body; accordingly, it is implicated in several other physiological functions, which include growth hormone release, gastric emptying, and body weight regulation. Ghrelin and GRLN-R expression are also found in the pancreas, suggesting a local physiological role. Accordingly, several recent studies now point towards an important role for ghrelin and its receptor in the regulation of blood glucose homeostasis, which is the main focus of this review. Several mechanisms of this regulation by ghrelin have been proposed, and one possibility is through the regulation of insulin secretion. Despite some controversy, most studies suggest that ghrelin exerts an inhibitory effect on insulin secretion, resulting in increased circulating glucose levels. Ghrelin may thus be a diabetogenic factor. Obesity-related type 2 diabetes has become an increasingly important health problem, almost reaching epidemic proportions in the world; therefore, antagonists of the ghrelin-GOAT signaling pathway, which will tackle both energy- and glucose homeostasis, may be considered as promising new therapies for this disease. PMID- 22783042 TI - Can zinc enhance response interferon therapy for patients with HCV-related liver disease? AB - Patients with liver disease may be at risk of zinc depletion. Zinc supplementation has been shown to contribute to inhibition of liver fibrosis and improvement in hepatic encephalopathy. However, little is known about the anti inflammatory effect of zinc on hepatitis C virus (HCV)-related chronic liver disease. The standard of care for chronic HCV has improved markedly since the approval of interferon (IFN) therapy more than a decade ago. Over the past 20 years, IFN therapy has improved to more effectively eliminate the virus, progressing from single IFN therapy to combination therapy with ribavirin (RBV) and finally to pegylated IFN (PEG-IFN) therapy. However, even combined therapy with PEG-IFN and RBV for 48 wk is unable to eliminate the virus in some 40% of hepatitis C cases, particularly those with genotype 1b and high viral load. Treatment options for patients who have relapsed or are refractory to treatment with PEG-IFN and RBV therefore need to be critically assessed. This paper overviews the relationship between chronic liver disease and zinc metabolism. PMID- 22783044 TI - Mangiferin, a natural xanthone, accelerates gastrointestinal transit in mice involving cholinergic mechanism. AB - AIM: To investigate the effects of mangiferin on gastrointestinal transit (GIT) in normal and constipated mice, together with the possible mechanism. METHODS: Intragastrically-administered charcoal meal was used to measure GIT in overnight starved Swiss mice. In the first experiments, mangiferin (3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg, po) or tegaserod (1 mg/kg, ip) were administered 30 min before the charcoal meal to study their effects on normal transit. In the second series, mangiferin (30 mg/kg) was tested on delayed GIT induced by several different pharmacological agonists (morphine, clonidine, capsaicin) or antagonists (ondansetron, verapamil, and atropine) whereas in the third series, mangiferin (30 mg/kg, 100 mg/kg and 300 mg/kg) or tegaserod (1 mg/kg) were tested on 6 h fecal pellets outputted by freely fed mice. The ratio of wet to dry weight was calculated and used as a marker of fecal water content. RESULTS: Mangiferin administered orally significantly (P < 0.05) accelerated GIT at 30 mg/kg and 100 mg/kg (89% and 93%, respectively), similarly to 5-hydroxytryptamine(4) (5-HT(4)) agonist tegaserod (81%) when compared to vehicle-treated control (63%). Co administered mangiferin (30 mg/kg) totally reversed the inhibitory effect of opioid agonist morphine, 5-HT(3)-receptor antagonist ondansetron and transient receptor potential vanilloid-1 receptor agonist capsaicin on GIT, but only to a partial extent with the GIT-delay induced by alpha(2)-adrenoceptor agonist clonidine, and calcium antagonist verapamil. However, co-administered atropine completely blocked the stimulant effect of mangiferin on GIT, suggesting the involvement of muscarinic acetylcholine receptor activation. Although mangiferin significantly enhanced the 6 h fecal output at higher doses (245.5 +/- 10.43 mg vs 161.9 +/- 10.82 mg and 227.1 +/- 20.11 mg vs 161.9 +/- 10.82 mg of vehicle treated control, at 30 and 100 mg/kg, P < 0.05, respectively), the effect of tegaserod was more potent (297.4 +/- 7.42 mg vs 161.9 +/- 10.82 mg of vehicle treated control, P < 0.05). Unlike tegaserod, which showed an enhanced water content in fecal pellets (59.20% +/- 1.09% vs 51.44% +/- 1.19% of control, P < 0.05), mangiferin evidenced no such effect, indicating that it has only a motor and not a secretomotor effect. CONCLUSION: Our data indicate the prokinetic action of mangiferin. It can stimulate the normal GIT and also overcome the drug induced transit delay, via a cholinergic physiological mechanism. PMID- 22783043 TI - Gastroenterostoma after Billroth antrectomy as a premalignant condition. AB - Gastric stump carcinoma (GSC) following remote gastric surgery is widely recognized as a separate entity within the group of various types of gastric cancer. Gastrectomy is a well established risk factor for the development of GSC at a long time after the initial surgery. Both exo- as well as endogenous factors appear to be involved in the etiopathogenesis of GSC, such as achlorhydria, hypergastrinemia and biliary reflux, Epstein-Barr virus and Helicobacter pylori infection, atrophic gastritis, and also some polymorphisms in interleukin-1beta and maybe cyclo-oxygenase-2. This review summarizes the literature of GSC, with special reference to reliable early diagnostics. In particular, dysplasia can be considered as a dependable morphological marker. Therefore, close endoscopic surveillance with multiple biopsies of the gastroenterostomy is recommended. Screening starting at 15 years after the initial ulcer surgery can detect tumors at a curable stage. This approach can be of special interest in Eastern European countries, where surgery for benign gastroduodenal ulcers has remained a practice for a much longer time than in Western Europe, and therefore GSC is found with higher frequency. PMID- 22783045 TI - Predictive value of 18F-fluorodeoxyglucose PET/CT for transarterial chemolipiodolization of hepatocellular carcinoma. AB - AIM: To investigate the correlation of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) with clinical features and the prediction of treatment response. METHODS: A total of 83 hepatocellular carcinoma (HCC) patients undergoing 18F-FDG PET before transarterial chemolipiodolization with systemic chemo-infusion between October, 2006 and May, 2009 were retrospectively enrolled. The patients included 68 men and 15 women (mean age, 60 +/- 10.7 years). The effect of (18)F-FDG-monitored PET uptake on clinical features and on the evaluated treatment response was ascertained with modified Response Evaluation Criteria in Solid Tumors. The PET parameters of maximal standardized uptake value of the tumor (Tsuv(max)), the ratio of the tumor maximal standardized uptake value (SUV) to the liver maximal SUV (Tsuv(max)/Lsuv(max)) and the ratio of tumor maximal SUV to the liver mean SUV (Tsuv(max)/Lsuv(mean)) were tested as predictive factors. RESULTS: Among the 3 SUV parameters, the Tsuv(max)/Lsuv(mean) ratio (cutoff value of 1.90) was significantly associated with tumor burden including tumor size, tumor number, alpha-fetoprotein levels and tumor stage (P < 0.001, P = 0.008, P = 0.011, P < 0.001, respectively). The objective response rates in patients with a high SUV ratio (>= 1.90) were significantly better than those with a low SUV ratio (< 1.90) (P = 0.020). The overall survival rates of patients exhibiting a low Tsuv(max)/Lsuv(mean) ratio (< 1.90) and those with a high SUV ratio (>= 1.90) was 38.2 and 10.3 mo, respectively (P < 0.01). However, the time to progression showed no significant difference between the groups (P = 0.15). CONCLUSION: 18F-FDG PET can be an important predictor of HCC treatment. In particular, the Tsuv(max)/Lsuv(mean) ratio (cutoff value of 1.90) can provide useful information in treatment prognosis for HCC patients treated with locoregional therapy. PMID- 22783046 TI - Effect of biologically active fraction of Nardostachys jatamansi on cerulein induced acute pancreatitis. AB - AIM: To determine if the fraction of Nardostachys jatamansi (NJ) has the potential to ameliorate the severity of acute pancreatitis (AP). METHODS: Mice were administered the biologically active fraction of NJ, i.e., the 4th fraction (NJ4), intraperitoneally, and then injected with the stable cholecystokinin analogue cerulein hourly for 6 h. Six hours after the last cerulein injection, the pancreas, lung, and blood were harvested for morphological examination, measurement of cytokine expression, and examination of neutrophil infiltration. RESULTS: NJ4 administration attenuated the severity of AP and lung injury associated with AP. It also reduced cytokine production and neutrophil infiltration and resulted in the in vivo up-regulation of heme oxygenase-1 (HO 1). Furthermore, NJ4 and its biologically active fraction, NJ4-2 inhibited the cerulein-induced death of acinar cells by inducing HO-1 in isolated pancreatic acinar cells. CONCLUSION: These results suggest that NJ4 may be a candidate fraction offering protection in AP and NJ4 might ameliorate the severity of pancreatitis by inducing HO-1 expression. PMID- 22783047 TI - Effect of Yiguanjian decoction on cell differentiation and proliferation in CCl4 treated mice. AB - AIM: To investigate the cellular mechanisms of action of Yiguanjian (YGJ) decoction in treatment of chronic hepatic injury. METHODS: One group of mice was irradiated, and received enhanced green fluorescent protein (EGFP)-positive bone marrow transplants followed by 13 wk of CCl4 injection and 6 wk of oral YGJ administration. A second group of Institute for Cancer Research mice was treated with 13 wk of CCl4 injection and 6 wk of oral YGJ administration. Liver function, histological changes in the liver, and Hyp content were analyzed. The expression of alpha-smooth muscle actin (alpha-SMA), F4/80, albumin (Alb), EGFP, mitogen activated protein kinase-2 (PKM2), Ki-67, alpha fetoprotein (AFP), monocyte chemotaxis protein-1 and CC chemokine receptor 2 were assayed. RESULTS: As hepatic damage progressed, EGFP-positive marrow cells migrated into the liver and were mainly distributed along the fibrous septa. They showed a conspicuous coexpression of EGFP with alpha-SMA and F4/80 but no coexpression with Alb. Moreover, the expression of PKM2, AFP and Ki-67 was enhanced dynamically and steadily over the course of liver injury. YGJ abrogated the increases in the number of bone marrow-derived fibrogenic cells in the liver, inhibited expression of both progenitor and mature hepatocyte markers, and reduced fibrogenesis. CONCLUSION: YGJ decoction improves liver fibrosis by inhibiting the migration of bone marrow cells into the liver as well as inhibiting their differentiation and suppressing the proliferation of both progenitors and hepatocytes in the injured liver. PMID- 22783048 TI - Carbon dioxide insufflation during colonoscopy in deeply sedated patients. AB - AIM: To compare the impact of carbon dioxide (CO2) and air insufflation on patient tolerance/safety in deeply sedated patients undergoing colonoscopy. METHODS: Patients referred for colonoscopy were randomized to receive either CO2 or air insufflation during the procedure. Both the colonoscopist and patient were blinded to the type of gas used. During the procedure, insertion and withdrawal times, caecal intubation rates, total sedation given and capnography readings were recorded. The level of sedation and magnitude of patient discomfort during the procedure was assessed by a nurse using a visual analogue scale (VAS) (0-3). Patients then graded their level of discomfort and abdominal bloating using a similar VAS. Complications during and after the procedure were recorded. RESULTS: A total of 142 patients were randomized with 72 in the air arm and 70 in the CO2 arm. Mean age between the two study groups were similar. Insertion time to the caecum was quicker in the CO2 group at 7.3 min vs 9.9 min with air (P = 0.0083). The average withdrawal times were not significantly different between the two groups. Caecal intubation rates were 94.4% and 100% in the air and CO2 groups respectively (P = 0.012). The level of discomfort assessed by the nurse was 0.69 (air) and 0.39 (CO2) (P = 0.0155) and by the patient 0.82 (air) and 0.46 (CO2) (P = 0.0228). The level of abdominal bloating was 0.97 (air) and 0.36 (CO2) (P = 0.001). Capnography readings trended to be higher in the CO2 group at the commencement, caecal intubation, and conclusion of the procedure, even though this was not significantly different when compared to readings obtained during air insufflation. There were no complications in both arms. CONCLUSION: CO2 insufflation during colonoscopy is more efficacious than air, allowing quicker and better cecal intubation rates. Abdominal discomfort and bloating were significantly less with CO2 insufflation. PMID- 22783049 TI - Intestinal alkaline phosphatase in the colonic mucosa of children with inflammatory bowel disease. AB - AIM: To investigate intestinal alkaline phosphatase (iAP) in the intestinal mucosa of children with inflammatory bowel disease (IBD). METHODS: Colonic biopsy samples were taken from 15 newly diagnosed IBD patients and from 10 healthy controls. In IBD patients, specimens were obtained both from inflamed and non inflamed areas. The iAP mRNA and protein expression was determined by reverse transcription-polymerase chain reaction and Western blotting analysis, respectively. Tissue localization of iAP and Toll-like receptor (TLR) 4 was investigated by immunofluorescent staining. RESULTS: The iAP protein level in the inflamed mucosa of children with Crohn's disease (CD) and ulcerative colitis (UC) was significantly decreased when compared with controls (both P < 0.05). Similarly, we found a significantly decreased level of iAP protein in the inflamed mucosa in CD compared with non-inflamed mucosa in CD (P < 0.05). In addition, the iAP protein level in inflamed colonic mucosa in patients with UC was decreased compared with non-inflamed mucosa in patients with CD (P < 0.05). iAP protein levels in the non-inflamed mucosa of patients with CD were similar to controls. iAP mRNA expression in inflamed colonic mucosa of children with CD and UC was not significantly different from that in non-inflamed colonic mucosa with CD. Expression of iAP mRNA in patients with non-inflamed mucosa and in controls were similar. Co-localization of iAP with TLR4 showed intense staining with a dotted-like pattern. iAP was present in the inflamed and non-inflamed mucosa of patients with CD, UC, and in control biopsy specimens, irrespective of whether it was present in the terminal ileum or in the colon. However, the fluorescent signal of TLR4 was more pronounced in the colon compared with the terminal ileum in all groups studied. CONCLUSION: Lower than normal iAP protein levels in inflamed mucosa of IBD patients may indicate a role for iAP in inflammatory lesions in IBD. Based on our results, administration of exogenous iAP enzyme to patients with the active form of IBD may be a therapeutic option. PMID- 22783050 TI - Incidence and clinical features of endoscopic ulcers developing after gastrectomy. AB - AIM: To determine the precise incidence and clinical features of endoscopic ulcers following gastrectomy. METHODS: A consecutive series of patients who underwent endoscopic examination following gastrectomy between 2005 and 2010 was retrospectively analyzed. A total of 78 patients with endoscopic ulcers and 759 without ulcers following gastrectomy were enrolled. We analyzed differences in patient age, sex, size of the lesions, method of operation, indications for gastric resection, and infection rates of Helicobacter pylori (H. pylori) between the nonulcer and ulcer groups. RESULTS: The incidence of endoscopic ulcers after gastrectomy was 9.3% and that of marginal ulcers was 8.6%. Ulcers were more common in patients with Billroth II anastomosis and pre-existing conditions for peptic ulcer disease (PUD). Infection rates of H. pyloridid not differ significantly between the two groups. The patients who underwent operations to treat PUD had lower initial levels of hemoglobin and higher rates of hospital admission. CONCLUSION: H. pylori was not an important factor in ulcerogenesis following gastrectomy. For patients who underwent surgery for PUD, clinical course of marginal ulcers was more severe. PMID- 22783051 TI - Two-stage resection for malignant colonic obstructions: the timing of early resection and possible predictive factors. AB - AIM: To study potential predictive factors for early radical resection in two stage resection for left malignant colonic obstruction. METHODS: Thirty-eight cases of left-sided obstructive colon cancer undergoing two-stage operations were reviewed between January 1998 and August 2008. Patients were classified into two groups (n = 19 each): early radical resection (interval <= 10 d) and late radical resection (interval > 10 d). Baseline demographics, post-diversion outcome, perioperative data, tumor characteristics, outcome and complications were analyzed. RESULTS: The baseline demographics revealed no differences except for less pre-diversion sepsis in the early group (P < 0.001) and more obstruction days in the late group (P = 0.009). The mean intervals of early and late radical resections were 7.9 +/- 1.3 d and 17.8 +/- 5.5 d, respectively (P < 0.001). After diversion, the presence of bowel sounds, flatus, removal of the nasogastric tube and the resumption of oral feeding occurred earlier in the early group. The operation time and duration of hospital stay were both significant reduced in the early group. Complication rates did not differ between groups. CONCLUSION: The earlier recovery of bowel function seems to be predictive of early radical resection. In contrast, pre-diversion sepsis and more obstruction days were predictive of delayed radical resection. PMID- 22783052 TI - Preoperative predictors of short-term survival after hepatectomy for multinodular hepatocellular carcinoma. AB - AIM: To investigate preoperative factors associated with poor short-term outcome after resection for multinodular hepatocellular carcinoma (HCC) and to assess the contraindication of patients for surgery. METHODS: We retrospectively analyzed 162 multinodular HCC patients with Child-Pugh A liver function who underwent surgical resection. The prognostic significance of preoperative factors was investigated by univariate analysis using the log-rank test and by multivariate analysis using the Cox proportional hazards model. Each independent risk factor was then assigned points to construct a scoring model to evaluate the indication for surgical intervention. A receiver operating characteristics (ROC) curve was constructed to assess the predictive ability of this system. RESULTS: The median overall survival was 38.3 mo (range: 3-80 mo), while the median disease-free survival was 18.6 mo (range: 1-79 mo). The 1-year mortality was 14%. Independent prognostic risk factors of 1-year death included prealbumin < 170 mg/L [hazard ratio (HR): 5.531, P < 0.001], alkaline phosphatase > 129 U/L (HR: 3.252, P = 0.005), alpha fetoprotein > 20 MUg/L (HR: 7.477, P = 0.011), total tumor size > 8 cm (HR: 10.543; P < 0.001), platelet count < 100 * 109/L (HR: 9.937, P < 0.001), and gamma-glutamyl transpeptidase > 64 U/L (HR: 3.791, P < 0.001). The scoring model had a strong ability to predict 1-year survival (area under ROC: 0.925, P < 0.001). Patients with a score >= 5 had significantly poorer short-term outcome than those with a score < 5 (1-year mortality: 62% vs 5%, P < 0.001; 1-year recurrence rate: 86% vs 33%, P < 0.001). Patients with score >= 5 had greater possibility of microvascular invasion (P < 0.001), poor tumor differentiation (P = 0.003), liver cirrhosis with small nodules (P < 0.001), and intraoperative blood transfusion (P = 0.010). CONCLUSION: A composite preoperative scoring model can be used as an indication of prognosis of HCC patients after surgical resection. Resection should be considered with caution in patients with a score >= 5, which indicates a contraindication for surgery. PMID- 22783053 TI - Electrical bioimpedance gastric motility measurement based on an electrical mechanical composite mechanism. AB - AIM: To introduce a bioimpedance gastric motility measurement method based on an electrical-mechanical composite concept and a preliminary clinical application. METHODS: A noninvasive gastric motility measurement method combining electrogastrogram (EGG) and impedance gastric motility (IGM) test was used. Preliminary clinical application studies of patients with functional dyspepsia (FD) and gastritis, as well as healthy controls, were carried out. Twenty-eight FD patients (mean age 40.9 +/- 9.7 years) and 40 healthy volunteers (mean age 30.9 +/- 7.9 years) were involved. IGM spectrum was measured for both the healthy subjects and FD patients, and outcomes were compared in the FD patients before treatment and 1 wk and 3 wk after treatment. IGM parameters were obtained from 30 erosive gastritis patients (mean age 50.5 +/- 13.0 years) and 40 healthy adults, and IGM and EGG results were compared in the gastritis patients before treatment and 1 wk after treatment. RESULTS: There were significant differences in the IGM parameters between the FD patients and healthy subjects, and FD patients had a poorer gastric motility [percentage of normal frequency (PNF) 70.8 +/- 25.5 in healthy subjects and 28.3 +/- 16.9 in FD patients, P < 0.01]. After 1 wk administration of domperidone 10 mg, tid, the gastric motility of FD patients was not improved, although the EGG of the patients had returned to normal. After 3 wk of treatment, the IGM rhythm of the FD patients became normal. There was a significant difference in IGM parameters between the two groups (PNF 70.4 +/- 25.5 for healthy subjects and 36.1 +/- 21.8 for gastritis patients, P < 0.05). The EGG rhythm of the gastritis patients returned to normal (frequency instability coefficient 2.22 +/- 0.43 before treatment and 1.77 +/- 0.19 one wk after treatment, P < 0.05) after 1 wk of treatment with sodium rabeprazole tablets, 10 mg, qd, po, qm, while some IGM parameters showed a tendency toward improvement but had not reached statistical significance. CONCLUSION: The electrical-mechanical composite measurement method showed an attractive clinical application prospect in gastric motility research and evaluation. PMID- 22783054 TI - Omega-3 polyunsaturated fatty acids promote liver regeneration after 90% hepatectomy in rats. AB - AIM: To evaluate the effectiveness of omega-3 polyunsaturated fatty acid (omega-3 PUFA) administration on liver regeneration after 90% partial hepatectomy (PH) in rats. METHODS: omega-3 PUFAs were intravenously injected in the omega-3 PUFA group before PH surgery. PH, sparing only the caudate lobe, was performed in both the control and the omega-3 PUFA group. Survival rates, liver weight/body weight ratios, liver weights, HE staining, transmission electron microscope imaging, nuclear-associated antigen Ki-67, enzyme-linked immunosorbent assay and signal transduction were evaluated to analyze liver regeneration. RESULTS: All rats in the control group died within 30 h after hepatectomy. Survival rates in the omega 3 PUFA group were 20/20 at 30 h and 4/20 1 wk after PH. Liver weight/body weight ratios and liver weights increased significantly in the omega-3 PUFA group. The structure of sinusoidal endothelial cells and space of Disse was greatly restored in the omega-3 PUFA group compared to the control group after PH. In the omega-3 PUFA group, interleukin (IL)-4 and IL-10 levels were significantly increased whereas IL-6 and tumor necrosis factor-alpha levels were dramatically decreased. In addition, activation of protein kinase B (Akt) and of signal transducer and activator of transcription 3 signaling pathway were identified at an earlier time after PH in the omega-3 PUFA group. CONCLUSION: Omega-3 polyunsaturated fatty acids may prevent acute liver failure and promote liver regeneration after 90% hepatectomy in rats. PMID- 22783055 TI - Expression and significance of homeodomain protein Cdx2 in gastric carcinoma and precancerous lesions. AB - AIM: To investigate the expression and significance of caudal-related homeobox transcription factor (Cdx2) in gastric carcinoma (GC) and precancerous lesions. METHODS: The expression of Cdx2 in GC, precancerous lesions and normal gastric mucosa were detected using immunohistochemical method. Hematoxylin and eosin staining, alcian blue/periodic acid-schiff and high iron diamine/alcian blue staining were used to classify intestinal metaplasia (IM) and GC. RESULTS: Cdx2 was not detected in normal gastric mucosa. Cdx2 expression was detected in 87.1% (101/116) of IM, 50% (36/72) of dysplasia and 48.2% (41/85) of GC. The Cdx2 expressing cells in IM were more prevalent than in dysplasia and carcinoma (P < 0.05). There was no relationship between Cdx2 expression and the classification of IM or the degree of dysplasia. Expression of Cdx2 was significantly higher in intestinal-type carcinoma than in diffuse and mixed-type carcinoma (P < 0.05). Positive expression of Cdx2 was mainly found in moderately to well differentiated GC. There was a negative association between nuclear Cdx2 expression and lymph node metastasis and tumor, nodes, metastasis stage of GC (P < 0.05). The patients with Cdx2-positive expression showed a higher survival rate than those with Cdx2 negative expression (P = 0.038). Multivariate analysis revealed that the expression of Cdx2 and lymph node metastasis were independent prognostic indicators of GC (P < 0.05). CONCLUSION: Cdx2 may be closely related to IM and the intestinal-type GC and implicate better biological behavior and outcome. Cdx2 is useful for predicting the prognosis of GC. PMID- 22783056 TI - Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma. AB - AIM: To investigate the frequency and clinical significance of the myeloid derived suppressor cells (MDSC) in human colorectal carcinoma (CRC). METHODS: Samples of peripheral blood and tumor tissue from 49 CRC patients were analyzed. Mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation and were subjected to a flow cytometry-based immunophenotypic analysis. RESULTS: A considerable increase in the percentage of CD33+HLA-DR- MDSCs was observed in the peripheral blood (1.89% +/- 0.75%) and tumor tissues (2.99% +/- 1.29%) of CRC patients as compared with that in the peripheral blood of healthy controls (0.54% +/- 0.35%). This expanded CD33+HLA-DR- subset exhibited immature myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Further studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis(P = 0.023), whereas that in tumor tissues was correlated with nodal/distant metastasis (P = 0.016/P = 0.047) and tumor stage (P = 0.028), suggesting the involvement of MDSCs in CRC tumor development. CONCLUSION: Characterization of MDSCs in CRC suggests the clinical significance of circulating and tumor-infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs. PMID- 22783058 TI - Lymphogranuloma venereum proctosigmoiditis is a mimicker of inflammatory bowel disease. AB - There has been an increasing prevalence of lymphogranuloma venereum (LGV) or Chlamydia trachomatis (C. trachomatis) cases among the men who have sex with men (MSM) population, particularly in Europe and North America. These cases may present with an incomplete or undisclosed history and proctosigmoiditis without characteristic adenopathy syndrome. During the initial evaluation and colonoscopy, there is a strong clinical and endoscopic suspicion of inflammatory bowel disease (IBD) by virtue of presentation and endoscopic and histological findings. The diagnosis of IBD is subsequently modified to LGV proctosigmoiditis when one or more of the following transpire: (1) there is failure of response to IBD therapy; (2) additional components of history (MSM/travel) may be identified; (3) return of initially performed Chlamydia antibody test is positive; and (4) response to antibiotics effective against Chlamydia. We describe three such cases initially suspected to be an inflammatory bowel disease and subsequently identified as C. trachomatis proctosigmoiditis. PMID- 22783057 TI - Protective effect of nitric oxide on hepatopulmonary syndrome from ischemia reperfusion injury. AB - AIM: To evaluate immunological protection of nitric oxide (NO) in hepatopulmonary syndrome and probable mechanisms of ischemia-reperfusion (IR) injury in rat liver transplantation. METHODS: Sixty-six healthy male Wistar rats were randomly divided into three groups (11 donor/recipient pairs). In group II, organ preservation solution was lactated Ringer's solution with heparin 10, 000/MUL at 4 degrees C. In groups I and III, the preservation solution added, respectively, L-arginine or N(G)-L-arginine methyl ester (L-NAME) (1 mmol/L) based on group II, and recipients were injected with L-arginine or L-NAME (50 mg/kg) in the anhepatic phase. Grafted livers in each group were stored for 6 h and implanted into recipients. Five rats were used for observation of postoperative survival in each group. The other six rats in each group were used to obtain tissue samples, and executed at 3 h and 24 h after transplantation. The levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-alpha and NO metabolites (NOx) were detected, and expression of NO synthase, TNF-alpha and intercellular adhesion molecule 1 (ICAM-1) was examined by triphosphopyridine nucleotide diaphorase histochemical and immunohistochemical staining. RESULTS: By supplementing L-arginine to strengthen the NO pathway, a high survival rate was achieved and hepatic function was improved. One-week survival rate of grafted liver recipients in group I was significantly increased (28.8 +/- 36.6 d vs 4 +/- 1.7 d, P < 0.01) as compared with groups II and III. Serum levels of ALT in group I were 2-7 times less than those in groups II and III (P < 0.01). The cyclic guanosine monophosphate (cGMP) levels in liver tissue and NOx in group I were 3-4 times higher than those of group II after 3 h and 24 h reperfusion, while in group III, they were significantly reduced as compared with those in group II (P < 0.01). The levels of TNF-alpha in group I were significantly lower than in group II after 3 h and 24 h reperfusion (P < 0.01), while being significantly higher in group III than group II (P < 0.01). Histopathology revealed more severe tissue damage in graft liver and lung tissues, and a more severe inflammatory response of the recipient after using NO synthase inhibitor, while the pathological damage to grafted liver and the recipient's lung tissues was significantly reduced in group I after 3 h and 24 h reperfusion. A small amount of constitutive NO synthase (cNOS) was expressed in liver endothelial cells after 6 h cold storage, but there was no expression of inducible NO synthase (iNOS). Expression of cNOS was particularly significant in vascular endothelial cells and liver cells at 3 h and 24 h after reperfusion in group II, but expression of iNOS and ICAM-1 was low in group I. There was diffuse strong expression of ICAM-1 and TNF-alpha in group III at 3 h after reperfusion. CONCLUSION: The NO/cGMP pathway may be critical in successful organ transplantation, especially in treating hepatopulmonary syndrome during cold IR injury in rat orthotopic liver transplantation. PMID- 22783059 TI - Diagnosis in bile acid-CoA: amino acid N-acyltransferase deficiency. AB - Cholate-CoA ligase (CCL) and bile acid-CoA: amino acid N-acyltransferase (BAAT) sequentially mediate bile-acid amidation. Defects can cause intrahepatic cholestasis. Distinction has required gene sequencing. We assessed potential clinical utility of immunostaining of liver for CCL and BAAT. Using commercially available antibodies against BAAT and CCL, we immunostained liver from an infant with jaundice, deficiency of amidated bile acids, and transcription-terminating mutation in BAAT. CCL was normally expressed. BAAT expression was not detected. Immunostaining may facilitate diagnosis in bile-acid amidation defects. PMID- 22783060 TI - Giant choledocholithiasis treated by mechanical lithotripsy using a gastric bezoar basket. AB - Mechanical lithotripsy (ML) is usually considered as a standard treatment option for large bile duct stones. However, it is impossible to retrieve oversized stones because the conventional lithotripsy basket may not be able to grasp the stone. However, there is no established endoscopic extraction method for such giant stone removal. We describe a case of successful extraction of a 4-cm large stone using a gastric bezoar basket. A 78-year-old woman had suffered from upper abdominal pain for 20 d. Contrast-enhanced computed tomogram revealed a 4-cm single stone in the distal common bile duct (CBD). Endoscopic stone retraction was decided upon and endoscopic papillary balloon dilation was performed using a large balloon. An attempt to capture the stone using a standard lithotripsy basket failed due to the large stone size. Subsequently, we used a gastric bezoar basket to successfully capture the stone. The stone was fragmented into small pieces and extracted. The stone was completely removed after two sessions of endoscopic retrograde cholangiopancreatography; each of which took 30 min. No complications occurred during or after the procedure. The patient was fully recovered and discharged on day 11 of hospitalization. ML using a gastric bezoar basket is a safe and effective retrieval method in select cases, and is considered as an alternative nonoperative option for the management of difficult CBD stones. PMID- 22783061 TI - Semi-Coke-Supported Mixed Metal Oxides for Hydrogen Sulfide Removal at High Temperatures. AB - To improve the desulfurization efficiency of sorbents at low cost, modified semi coke was used as the substrate for mixed metal oxides (ZFM; oxides of zinc [Zn], iron [Fe], and manganese [Mn]) in hot gas desulfurization. Performance of the prepared ZFM/modified semi-coke (MS) sorbents were evaluated in a fixed-bed reactor in the temperature range 400-550 degrees C. Results showed that the molar ratio of Mn to Zn, effect of the substrate, the calcination temperature, and the sulfidation temperature influenced the performance of the sorbents. Optimum conditions for the preparation of the ZFM/MS sorbents were molar ratio of Mn(NO(3))(2).6H(2)O, Zn(NO(3))(2), and Fe(NO(3))(3), 0.6:1:2; mass ratio of ZFM0.6 to modified semi-coke support, 1:1; and calcination temperature, 600 degrees C. The ZFM0.6/MS sorbent thus prepared exhibited the best sorption sulfur capacity of 27.46% at 450 degrees C. PMID- 22783062 TI - Properties of Cement Mortar Produced from Mixed Waste Materials with Pozzolanic Characteristics. AB - Waste materials with pozzolanic characteristics, such as sewage sludge ash (SSA), coal combustion fly ash (FA), and granulated blast furnace slag (GBS), were reused as partial cement replacements for making cement mortar in this study. Experimental results revealed that with dual replacement of cement by SSA and GBS and triple replacement by SSA, FA, and GBS at 50% of total cement replacement, the compressive strength (Sc) of the blended cement mortars at 56 days was 93.7% and 92.9% of the control cement mortar, respectively. GBS had the highest strength activity index value and could produce large amounts of CaO to enhance the pozzolanic activity of SSA/FA and form calcium silicate hydrate gels to fill the capillary pores of the cement mortar. Consequently, the Sc development of cement mortar with GBS replacement was better than that without GBS, and the total pore volume of blended cement mortars with GBS/SSA replacement was less than that with FA/SSA replacement. In the cement mortar with modified SSA and GBS at 70% of total cement replacement, the Sc at 56 days was 92.4% of the control mortar. Modifying the content of calcium in SSA also increased its pozzolanic reaction. CaCl(2) accelerated the pozzolanic activity of SSA better than lime did. Moreover, blending cement mortars with GBS/SSA replacement could generate more monosulfoaluminate to fill capillary pores. PMID- 22783063 TI - Comparison of Advection-Diffusion Models and Neural Networks for Prediction of Advanced Water Treatment Effluent. AB - An artificial neural network (ANN) can help in the prediction of advanced water treatment effluent and thus facilitate design practices. In this study, sets of 225 experimental data were obtained from a wastewater treatment process for the removal of phosphorus using oven-dried alum residuals in fixed-bed adsorbers. Five input variables (pH, initial phosphorus concentration, wastewater flow rate, porosity, and time) were used to test the efficiency of phosphorus removal at different times, and ANNs were then used to predict the effluent phosphorus concentration. Results of experiments that were conducted for different values of the input parameters made up the data used to train and test a multilayer perceptron using the back-propagation algorithm of the ANN. Values predicted by the ANN and the experimentally measured values were compared, and the accuracy of the ANN was evaluated. When ANN results were compared to the experimental results, it was concluded that the ANN results were accurate, especially during conditions of high phosphorus concentration. While the ANN model was able to predict the breakthrough point with good accuracy, the conventional advection diffusion equation was not as accurate. A parametric study conducted to examine the effect of the initial pH and initial phosphorus concentration on the effluent phosphorus concentration at different times showed that lower influent pH values are the most suitable for this advanced treatment system. PMID- 22783064 TI - An Integrated Statistical Approach to Compare Transcriptomics Data Across Experiments: A Case Study on the Identification of Candidate Target Genes of the Transcription Factor PPARalpha. AB - An effective strategy to elucidate the signal transduction cascades activated by a transcription factor is to compare the transcriptional profiles of wild type and transcription factor knockout models. Many statistical tests have been proposed for analyzing gene expression data, but most tests are based on pair wise comparisons. Since the analysis of microarrays involves the testing of multiple hypotheses within one study, it is generally accepted that one should control for false positives by the false discovery rate (FDR). However, it has been reported that this may be an inappropriate metric for comparing data across different experiments. Here we propose an approach that addresses the above mentioned problem by the simultaneous testing and integration of the three hypotheses (contrasts) using the cell means ANOVA model. These three contrasts test for the effect of a treatment in wild type, gene knockout, and globally over all experimental groups. We illustrate our approach on microarray experiments that focused on the identification of candidate target genes and biological processes governed by the fatty acid sensing transcription factor PPARalpha in liver. Compared to the often applied FDR based across experiment comparison, our approach identified a conservative but less noisy set of candidate genes with same sensitivity and specificity. However, our method had the advantage of properly adjusting for multiple testing while integrating data from two experiments, and was driven by biological inference. Taken together, in this study we present a simple, yet efficient strategy to compare differential expression of genes across experiments while controlling for multiple hypothesis testing. PMID- 22783065 TI - Cultural Characteristics of Ophiocordyceps heteropoda Collected from Korea. AB - Isolates of Ophiocordyceps heteropoda (Kobayasi) collected from Mt. Halla on Jeju do, Korea were tested for mycelial growth on different agar media and in the presence of different carbon and nitrogen sources. Similarly, isolates were also incubated at different temperatures as well as under continuous light and dark conditions. Growth was better on Hamada agar, basal medium, and malt-yeast agar, but poor on Czapek-Dox agar. Different carbon sources such as dextrin, saccharose, starch, lactose, maltose, fructose, and dextrose resulted in better growth. Complex organic nitrogen sources such as yeast extract and peptone revealed the most effective growth. Mycelial growth was best at 25C. The growth rate was faster in the dark than the light, but mycelial density was less compact in the dark. PMID- 22783066 TI - Enhancing Effect of Shimizuomyces paradoxus on Seed Germination and Seedling Growth of Canola, Plant Growth of Cucumber, and Harvest of Tomato. AB - Shimizuomyces paradoxus showed no inhibitory effect against plant pathogen fungi, such as Fusarium oxysporum f. sp. lycopersici and Alternaria solani. The S. paradoxus culture filtrate showed higher seed germination and seedling growth rates in canola than distilled water and potato-dextrose broth. A conidial suspension of 1.0*10(4)/mL resulted in the highest growth stimulating effects on total plant length, and fresh and dry weight of shoots and roots in cucumber, when compared to the highest suspension concentration. Total plant length and shoot weight increased with the foliar spray treatment, and root length and root weight increased by simultaneous treatments of soil drenching and foliar spray in cucumber. Lower concentrations of the S. paradoxus conidial suspension increased the harvest of tomato fruit. PMID- 22783067 TI - Assessment of Antioxidant and Phenolic Compound Concentrations as well as Xanthine Oxidase and Tyrosinase Inhibitory Properties of Different Extracts of Pleurotus citrinopileatus Fruiting Bodies. AB - Cellular damage caused by reactive oxygen species has been implicated in several diseases, thus establishing a significant role for antioxidants in maintaining human health. Acetone, methanol, and hot water extracts of Pleurotus citrinopileatus were evaluated for their antioxidant activities against beta carotene-linoleic acid and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, reducing power, ferrous ion-chelating abilities, and xanthine oxidase inhibitory activities. In addition, the tyrosinase inhibitory effects and phenolic compound contents of the extracts were also analyzed. Methanol and acetone extracts of P. citrinopileatus showed stronger inhibition of beta-carotene-linoleic acid compared to the hot water extract. Methanol extract (8 mg/mL) showed a significantly high reducing power of 2.92 compared to the other extracts. The hot water extract was more effective than the acetone and methanole extracts for scavenging DPPH radicals. The strongest chelating effect (92.72%) was obtained with 1.0 mg/mL of acetone extract. High performance liquid chromatography analysis detected eight phenolic compounds, including gallic acid, protocatechuic acid, chlorogenic acid, ferulic acid, naringenin, hesperetin, formononetin, and biochanin-A, in an acetonitrile and hydrochloric acid (5 : 1) solvent extract. Xanthine oxidase and tyrosinase inhibitory activities of the acetone, methanol, and hot water extracts increased with increasing concentration. This study suggests that fruiting bodies of P. citrinopileatus can potentially be used as a readily accessible source of natural antioxidants. PMID- 22783068 TI - Improvement of fungal cellulase production by mutation and optimization of solid state fermentation. AB - Spores of Aspergillus sp. SU14 were treated repeatedly and sequentially with Co(60) gamma-rays, ultraviolet irradiation, and N-methyl-N'-nitro-N nitrosoguanidine. One selected mutant strain, Aspergillus sp. SU14-M15, produced cellulase in a yield 2.2-fold exceeding that of the wild type. Optimal conditions for the production of cellulase by the mutant fungal strain using solid-state fermentation were examined. The medium consisted of wheat-bran supplemented with 1% (w/w) urea or NH(4)Cl, 1% (w/w) rice starch, 2.5 mM MgCl(2), and 0.05% (v/w) Tween 80. Optimal moisture content and initial pH was 50% (v/w) and 3.5, respectively, and optimal aeration area was 3/100 (inoculated wheat bran/container). The medium was inoculated with 25% 48 hr seeding culture and fermented at 35C for 3 days. The resulting cellulase yield was 8.5-fold more than that of the wild type strain grown on the basal wheat bran medium. PMID- 22783069 TI - Inhibition Effects of Silver Nanoparticles against Powdery Mildews on Cucumber and Pumpkin. AB - Powdery mildew is one of the most devastating diseases in cucurbits. Crop yield can decline as the disease severity increases. In this study, we evaluated the effect of silver nanoparticles against powdery mildew under different cultivation conditions in vitro and in vivo . Silver nanoparticles (WA-CV-WA13B) at various concentrations were applied before and after disease outbreak in plants to determine antifungal activities. In the field tests, the application of 100 ppm silver nanoparticles showed the highest inhibition rate for both before and after the outbreak of disease on cucumbers and pumpkins. Also, the application of 100 ppm silver nanoparticles showed maximum inhibition for the growth of fungal hyphae and conidial germination in in vivo tests. Scanning electron microscope results indicated that the silver nanoparticles caused detrimental effects on both mycelial growth and conidial germination. PMID- 22783070 TI - Screening wild yeast strains for alcohol fermentation from various fruits. AB - Wild yeasts on the surface of various fruits including grapes were surveyed to obtain yeast strains suitable for fermenting a novel wine with higher alcohol content and supplemented with rice starch. We considered selected characteristics, such as tolerance to alcohol and osmotic pressure, capability of utilizing maltose, and starch hydrolysis. Among 637 putative yeast isolates, 115 strains exhibiting better growth in yeast-peptone-dextrose broth containing 30% dextrose, 7% alcohol, or 2% maltose were selected, as well as five alpha-amylase producers. Nucleotide sequence analysis of the 26S rDNA gene classified the strains into 13 species belonging to five genera; Pichia anomala was the most prevalent (41.7%), followed by Wickerhamomyces anomalus (19.2%), P. guilliermondii (15%), Candida spp. (5.8%), Kodamaea ohmeri (2.5%), and Metschnikowia spp. (2.5%). All of the alpha-amylase producers were Aureobasidium pullulans. Only one isolate (NK28) was identified as Saccharomyces cerevisiae. NK28 had all of the desired properties for the purpose of this study, except alpha-amylase production, and fermented alcohol better than commercial wine yeasts. PMID- 22783071 TI - A Protective Mechanism in Lungs of Rats Experimentally Infected with Aspergillus fumigatus. AB - Aspergillus fumigatus is associated with invasive disease aspergillosis in immunocompromised individuals. The major aim of this study was to investigate the biochemical and immunological responses of male Wistar rats against A. fumigatus experimentally-induced pulmonary fungal infection. Nostril experimental exposure of male Wistar rats to a high dose of A. fumigatus freeze-dried preparation for only 24 hr resulted in a significant increase in levels of catalase, nitric oxide and lipid peroxide in lung homogenates, compared to those of the control animals. However, the oxidative status of the lungs of rats challenged with killed fungus did not change significantly, except for the stimulation in the level of lipid peroxide. IgG level was significantly elevated only in rats that received two low doses of fungus, compared to unexposed animals (p<0.005). Examining the lung of rats exposed to A. fumigatus revealed no abnormal changes, except for pus in bronchial lumen spaces and per bronchial inflammation. Histologically, large numbers of granuloma cells were evident in the lungs of challenged rats, while no granuloma formation was evident in the lungs of rats exposed to killed fungus. PMID- 22783072 TI - Hypolipidemic Activities of Dietary Pleurotus ostreatus in Hypercholesterolemic Rats. AB - This work was conducted to investigate dietary supplementation of oyster mushroom fruiting bodies on biochemical and histological changes in hyper and normocholesterolemic rats. Six-week old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. Feeding a diet containing a 5% powder of Pleurotus ostreatus fruiting bodies to hypercholesterolemic rats reduced plasma total cholesterol, triglyceride, low-density lipoprotein (LDL), total lipid, phospholipids, and LDL/high-density lipoprotein ratio by 30.18, 52.75, 59.62, 34.15, 23.89, and 50%, respectively. Feeding oyster mushrooms also significantly reduced body weight in hypercholesterolemic rats. However, it had no adverse effects on plasma albumin, total bilirubin, direct bilirubin, creatinin, blood urea nitrogen, uric acid, glucose, total protein, calcium, sodium, potassium, chloride, inorganic phosphate, magnesium, or enzyme profiles. Feeding mushroom increased total lipid and cholesterol excretion in feces. The plasma lipoprotein fraction, separated by agarose gel electrophoresis, indicated that P. ostreatus significantly reduced plasma beta and pre-beta-lipoprotein but increased alpha-lipoprotein. A histological study of hepatic cells by conventional hematoxylin-eosin and oil red O staining revealed normal findings for mushroom-fed hypercholesterolemic rats. These results suggest that a 5% P. ostreatus diet supplement provided health benefits by acting on the atherogenic lipid profile in hypercholesterolemic rats. PMID- 22783073 TI - First Report of Botrytis cinerea as a Postharvest Pathogen of Blueberry in Korea. AB - Gray mold of blueberry caused by Botrytis sp. is reported for the first time in Korea. A detailed description of the fungus is given, along with its rDNA internal transcribed spacer sequence. The fungus was identified as Botrytis cinerea based on mycological characteristics and molecular data. PMID- 22783074 TI - Two new records of the lichen genus placynthiella elenkin in South Korea. AB - This study describes two new records of the lichen genus Placynthiella (P. hyporhoda and P. icmalea) from South Korea. A brief taxonomic description and comments are provided for the new records. An artificial key is also provided for known species of this genus in South Korea. PMID- 22783075 TI - First Report of Stem Rot on Asiatic Dayflower (Commelina communis L.) Caused by Sclerotium rolfsii in Korea. AB - Stem rot was found for the first time on the Asiatic dayflower plant (Commelina communis L.) in Korea. A detailed description of this Korean specimen is given, along with its rDNA internal transcribed spacer sequence. The fungus was identified as Sclerotium rolfsii Saccardo based on mycological characteristics and molecular data. PMID- 22783076 TI - A new species of the genus euphoriomyces (laboulbeniales ascomycotina) collected in Korea. AB - One new species of the genus Euphoriomyces was collected on Scaphisoma rufum Achard (Scaphidiidae) in South Korea. Euphoriomyces chaekyui sp. nov. is unique in having a single terminal phialide shaped an elongated cylindrical form on the distal portion of the main axis. PMID- 22783077 TI - A lichen genus porpidia (porpidiaceae) from South Korea. AB - Taxonomic study of the crustose lichen Porpidia was performed in this paper. Three species are described, including two recorded species and one new record: Porpidia macrocarpa (DC.) Hertel & A. J. Schwab. A description of each species is presented along with morphological, anatomic, and chemical characteristics. A key to the identification of species of Porpidia is also presented. PMID- 22783078 TI - Enhanced Expression of Glucose 2-Oxidase in Phlebia tremellosa by Addition of Phthalates. AB - Most fungi possess several hydrogen peroxide-generating enzymes, glucose oxidase and pyranose oxidase. Pyranose oxidase can use glucose as its substrate to generate hydrogen peroxide. White rot fungi, which degrade diverse recalcitrant compounds, contain lignin-degrading enzymes, and lignin peroxidase and manganese peroxidase require hydrogen peroxide for their enzymatic reactions. In this study, we isolated a cDNA fragment of pyranose oxidase from Phlebia tremellosa using PCR and examined its expression under the degradation conditions of diethylphthalate (DEP). Pyranose oxidase expression was enhanced up to 30% by the addition of DEP, and this result supports the possible involvement of pyranose oxidase in the degradation of recalcitrant compounds. PMID- 22783079 TI - Digestion Pattern of Antihypertensive Angiotensin I-Converting Enzyme Inhibitory Peptides from Saccharomyces cerevisiae in a Successive Simulated Gastricintestinal Bioreactor. AB - A cell-free extract of Saccharomyces cerevisiae containing the angiotensin I converting enzyme (ACE) inhibitory peptide was treated in a successive simulated gastric-intestinal bioreactor (step 1: amylase digestion, step 2: gastric fluid digestion, step 3: intestinal fluid digestion) to illustrate the absorption pattern of antihypertensive ACE inhibitory peptide, and the ACE inhibitory activities of each step were determined. Total ACE inhibitory activities of step 1, step 2, and step 3 were 55.96%, 80.09%, and 76.77%, respectively. The peptide sequence of each steps was analyzed by MS/MS spectrophotometry. Eleven kinds of representative peptide sequences were conserved in each step, and representative new peptides including RLPTESVPEPK were identified in step 3. PMID- 22783080 TI - Multi-loci Molecular Characterisation of Endophytic Fungi Isolated from Five Medicinal Plants of Meghalaya, India. AB - The phylogenetic relationships of the most dominant and morphologically cryptic endophytic fungal isolates from each of five selected medicinal plants, namely Potentilla fulgens, Osbeckia stellata, Osbeckia chinensis, Camellia caduca, and Schima khasiana of the biodiversity rich state of Meghalaya, were assessed with random amplification of polymorphic DNA and PCR-restriction fragment length polymorphism profiles. Sequencing of the internal transcribed spacer 1, small subunit rRNA and partial beta-tubulin gene fragments was also conducted to determine the phylogenetic relationships of these isolates with fungal sequences available in Genbank, NCBI. The identity of the fungal isolates is suggested based on the molecular phylogenetic data. PMID- 22783081 TI - The Distribution of Cytoplasm and Nuclei within the Extra-radical Mycelia in Glomus intraradices, a Species of Arbuscular Mycorrhizal Fungi. AB - Nuclear distribution within the extra-radical fungal structures and during spore production in the arbuscular mycorrhizae fungus Glomus intraradices was examined using an in vitro monoxenic culture system. A di-compartmental monoxenic culture system was modified using a nitrocellulose membrane and a coverglass slip for detailed observations. Nuclear distribution was observed using the fluorescent DNA binding probes SYBR Green I and DAPI. Both septate and non-septate mycelial regions were observed, but cytoplasmic contents were only found within non septate mycelia. Nuclear fluorescent staining revealed that the non-septate hyphal region contained nuclei only with cytoplasm, and that nuclear distribution was limited by septa. Swollen hyphal bodies were often associated with septate and empty-looking hyphae. Cytoplasmic contents filled the swollen hyphal body from the non-septate hyphal region following removal of the septa. As a consequence, the swollen body developed into a new spore. These observations provide understanding about the distribution of AM fungal nuclei within extra radical mycelia and during spore formation. The results suggest a mechanism by which the development of a cytoplasm-containing mycelium is controlled by the formation or removal of septa to efficiently maintain and proliferate essential contents. This mechanism may provide a survival strategy to the fungus. PMID- 22783082 TI - Growth and Cultural Characteristics of Ophiocordyceps longissima Collected in Korea. AB - We investigated the effect of nutritional and environmental factors on Ophiocordyceps longissima mycelial growth. The longest colony diameter was observed on Schizophyllum (mushroom) genetics complete medium plus yeast extract, Schizophyllum (mushroom) genetics minimal medium, and Sabouraud dextrose agar (SDA); however, malt-extract yeast-extract agar, SDA plus yeast extract, yeast extract malt-extract peptone dextrose agar, SDA, oatmeal agar, and potato dextrose agar showed higher mycelia density. A temperature of 25C was optimum and 7.0 was the optimum pH for mycelial growth. Colony diameter was similar under light and dark conditions. Maltose and yeast extract showed the highest mycelial growth among carbon and nitrogen sources respectively. The effect of mineral salts was less obvious; however, K(3)PO(4) showed slightly better growth than that of the other mineral salts tested. Among all nutrition sources tested, complex organic nitrogen sources such as yeast extract, peptone, and tryptone were best for mycelial growth of O. longissima. Ophiocordyceps longissima composite medium, formulated by adding maltose (2% w/v), yeast extract (1% w/v), and K(3)PO(4) (0.05% w/v) resulted in slightly longer colony diameter. In vitro mycelial O. longissima growth was sustainable and the production of fruiting bodies could be used for commercial purposes in the future. PMID- 22783083 TI - Optimal Culture Conditions for Mycelial Growth of Lignosus rhinocerus. AB - Lignosus rhinocerus is a macrofungus that belongs to Polyporaceae and is native to tropical regions. This highly priced mushroom has been used as folk medicine to treat diseases by indigenous people. As a preliminary study to develop a culture method for edible mushrooms, the cultural characteristics of L. rhinocerus were investigated in a range of culture media under different environmental conditions. Mycelial growth of this mushroom was compared on culture media composed of various carbon and nitrogen sources in addition to C/N ratios. The optimal conditions for mycelial growth were 30C at pH 6 and 7. Rapid mycelial growth of L. rhinocerus was observed on glucose-peptone and yeast extract peptone dextrose media. Carbon and nitrogen sources promoting mycelial growth of L. rhinocerus were glucose and potassium nitrate, respectively. The optimum C/N ratio was approximately 10 : 1 using 2% glucose supplemented as a carbon source in the basal media. PMID- 22783084 TI - Antihyperlipidemic Effect of Dietary Lentinus edodes on Plasma, Feces and Hepatic Tissues in Hypercholesterolemic Rats. AB - We investigated diet supplementation with shiitake mushroom fruiting bodies on biochemical and histological changes in hypercholesterolemic rats. Six-wk old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. A diet containing 5% Lentinus edodes fruiting bodies given to hypercholesterolemic rats reduced plasma total cholesterol, triglyceride, low density lipoprotein (LDL), total lipid, phospholipids, and the LDL/high-density lipoprotein ratio by 34.33, 53.21, 75.00, 34.66, 25.73, and 71.43%, respectively. Feeding mushroom also significantly reduced body weight in hypercholesterolemic rats. However, it had no detrimental effects on plasma albumin, total bilirubin, direct bilirubin, creatinine, blood urea nitrogen, uric acid, glucose, total protein, calcium, sodium, potassium, chloride, inorganic phosphate, magnesium, or enzyme profiles. Feeding mushroom increased total lipid and cholesterol excretion in feces. The plasma lipoprotein fraction, separated by agarose gel electrophoresis, indicated that L. edodes significantly reduced plasma beta and pre-beta-lipoprotein but increased alpha-lipoprotein. A histological study of hepatic cells by conventional hematoxylin-eosin and oil red-O staining showed normal findings for mushroom-fed hypercholesterolemic rats. These results suggest that shiitake mushrooms could be recommended as a natural cholesterol lowering substance in the diet. PMID- 22783085 TI - Evaluation of ten wild nigerian mushrooms for amylase and cellulase activities. AB - Amylases and cellulases are important enzymes that can be utilized for various biological activities. Ten different wild Nigerian mushrooms (Agaricus blazei, Agaricus sp., Corilopsis occidentalis, Coriolus versicolor, Termitomyces clypeatus, Termitomyces globulus, Pleurotus tuber-regium, Podoscypha bolleana, Pogonomyces hydnoides, and Nothopanus hygrophanus) were assayed for production of these secondary metabolites. The results revealed that most of the tested wild fungi demonstrated very good amylase and cellulase activities. With the incorporation of carboxymethyl-cellulose (a carbon source) into the culture medium, Agaricus blazei had the highest amylolytic activity of 0.60 unit/mL (at 25C, pH 6.8). This was followed in order by P. tuber-regium and Agaricus sp. with 0.42 and 0.39 unit/mL, respectively (p <= 0.05). Maltose and sucrose supplementation into the submerged liquid medium made N. hygrophanus and P. hydnoides to exhibit very low amylase activities of 0.09 and 0.11 unit/mL, respectively. Introducing peptone (an organic nitrogen source) into the basal medium enhanced the ability of C. versicolor to produce a cellulase value of 0.74 unit/mL. Other organic nitrogen sources that supported good cellulase activities were yeast extract and urea. Sodium nitrate (inorganic nitrogen source) generally inhibited cellulase production in all mushrooms. The best carbon source was carboxymethyl-cellulose, which promoted very high cellulase activity of 0.67 unit/mL in C. versicolor, which was followed in order by P. tuber-regium, T. chypeatus, and C. occidentalis (p <= 0.05). Sucrose was the poorest carbon compound, supporting the lowest values of 0.01, 0.01, and 0.14 unit/mL in P. hydnoides, A. blazei, and Agaricus sp., respectively. PMID- 22783086 TI - Physiological Functionalities of Vitis hybrid (Sheridan)-Rubus coreanus Red Wine Made by Saccharomyces cerevisiae. AB - Vitis hybrid (Sheridan)-Robus coreanus red wine was vinified by fermentation of a mixture of Vitis hybrid and Robus coreanus must at 25C for 10 days. The Vitis hybrid-Robus coreanus red wine had ethanol contents of 10.9%. It had high antihypertensive angiotensin I-converting enzyme (ACE) inhibitory activity of 57.8% and antioxidant activity of 64.8%. Changes in the physicochemical properties and functionality of the Vitis hybrid-Robus coreanus red wine was investigated during a post-fermentation period of three months. The ACE inhibitory activity of the red wine increased as the post-fermentation period prolonged, and showed the highest ACE inhibitory activity of 70.4% 60 days post fermentation. However, the antioxidant activity declined significantly to 47.2% during the post-fermentation period of 60 days. In terms of sensory evaluation, the Vitis hybrid-Robus coreanus red wine had the best acceptability 60 days post fermentation. PMID- 22783087 TI - Use of Dactylaria brochopaga, a Predacious Fungus, for Managing Root-Knot Disease of Wheat (Triticum aestivum) Caused by Meloidogyne graminicola. AB - A laboratory experiment was conducted to study the induction of constricting rings and test predation of Dactylaria brochopaga isolates against second stage juveniles (J2s) of Meloidogyne graminicola. Among the five fungal isolates, isolate D showed the greatest number of predatory rings and, consequently, trapped the maximum number of M. graminicola J2s in dual cultures. Another pot experiment was conducted to study the effect of D. brochopaga (isolate D) on the management of wheat root-knot disease. Applying a mass culture (10 g/pot) and a spore suspension of the fungus with and without cow dung manure to soil infested with 2,000 M. graminicola juveniles significantly improved plant height, root length, weights of shoots, roots, panicles and grains per hill compared to those in the control. Moreover, the fungus significantly reduced the number of root knots, the number of egg masses, juveniles, and females per hill compared to those in the control. Bio-efficacy of the fungus was heightened when the mass culture and a spore suspensions were used in combination with cow dung manure to improve the plant growth parameters and reduce the number of root-knot and reproductive factors. Further investigations should be conducted to identify the impact of this fungus in the field. PMID- 22783088 TI - Detection of Extracellular Enzyme Activities in Ganoderma neo-japonicum. AB - The ability of Ganoderma to produce extracellular enzymes, including beta glucosidase, cellulase, avicelase, pectinase, xylanase, protease, amylase, and ligninase was tested in chromogenic media. beta-glucosidase showed the highest activity, among the eight tested enzymes. In particular, Ganoderma neo-japonicum showed significantly stronger activity for beta-glucosidase than that of the other enzymes. Two Ganoderma lucidum isolates showed moderate activity for avicelase; however, Ganoderma neo-japonicum showed the strongest activity. Moderate ligninase activity was only observed in Ganoderma neo-japonicum. In contrast, pectinase, amylase, protease, and cellulase were not present in Ganoderma. The results show that the degree of activity of the tested enzymes varied depending on the Ganoderma species tested. PMID- 22783089 TI - Heterologous Expression of Endo-1,4-beta-xylanaseA from Phanerochaete chrysosporium in Pichia pastoris. AB - The cDNA of endo-1,4-beta-xylanaseA, isolated from Phaenerocheate chrysosporium was expressed in Pichia pastoris. Using either the intrinsic leader peptide of XynA or the alpha-factor signal peptide of Saccharomyces cerevisiae, xylanaseA is efficiently secreted into the medium at maximum concentrations of 1,946 U/L and 2,496 U/L, respectively. PMID- 22783090 TI - Enzyme Activity of Cenococcum geophilum Isolates on Enzyme-specific Solid Media. AB - Enzyme activities of Cenococcum geophilum isolates were examined on enzyme specific solid media. Deoxyribonuclease, phosphatase, and urease were detected in all isolates, whereas cellulase was not detected in any of the isolates. Variations in enzyme activities of amylase, caseinolysis, gelatinase, lipase, and ribonuclease were observed among isolates. PMID- 22783091 TI - Optimal Media Conditions for the Detection of Extracellular Cellulase Activity in Ganoderma neo-japonicum. AB - To determine the optimal media conditions for the detection of the extracellular cellulase activity in Ganoderma neo-japonicum, we varied three media conditions: dye reagent, pH, and temperature. We evaluated the use of four dyes, Congo red, phenol red, remazol brilliant blue, and trypan blue. To observe the effect of pH on the chromogenic reaction, we tested media ranging from 4.5 to 8.0. To research the effect of temperature on the clear zone and the fungus growing zone, we tested temperatures ranging from 15 to 35C. On the whole, the best protocol called for Ganoderma neo-japonicum transfer onto media containing Congo red with a pH of 7.0, followed by incubation at 25C for 5 days. Our results will be useful to researchers who study extracellular enzyme activity in Ganoderma neo japonicum. PMID- 22783092 TI - Regeneration of ectomycorrhizal fungal isolates following deep freezer storage. AB - Mycelial growth and survival ratio of ectomycorrhizal fungi were determined after storage at -70C for 1, 3, or 6 mon. Seventeen of 23 ectomycorrhizal fungi did not survive after storage for more than 6 mon, whereas Cenococcum geophilum, Lepista nuda, and some species of Rhizopogon and Suillus did survive. PMID- 22783093 TI - Antihypertensive Angiotensin I-Converting Enzyme Inhibitory Activity and Antioxidant Activity of Vitis hybrid-Vitis coignetiae Red Wine Made with Saccharomyces cerevisiae. AB - A Vitis hybrid-Vitis coignetiae red wine was vinified by fermentation of a mixture of a Vitis hybrid-Vitis coignetiae must with Saccharomyces cerevisiae KCTC 7904 at 25C for 10 days. The Vitis hybrid-Vitis coignetiae red wine showed high antihypertensive angiotensin I-converting enzyme (ACE) inhibitory activity (67.8%) and antioxidant activity (76.7%). The antihypertensive ACE inhibitor in the Vitis hybrid-Vitis coignetiae red wine was partially purified by solid phase extraction chromatography, and its ACE inhibitory activity yielded an IC(50) of 1.8 mg/mL. Six kinds of oligopeptides, including five new kinds, were contained in the partially purified ACE inhibitor fraction from the red wine after 10 days of fermentation. Antioxidant activity decreased significantly from 76.7% to 40.5% when the post-fermentation period was prolonged to 30 days. PMID- 22783094 TI - First Report of Rhizopus oryzae as a Postharvest Pathogen of Apple in Korea. AB - Soft rot in apple caused by Rhizopus oryzae was found for the first time in Korea. A detailed description of the specimen is given along with its internal transcribed spacer rDNA sequence. The fungus was identified as Rhizopus oryzae based on the mycological characteristics, molecular data, and pathogenicity testing. PMID- 22783096 TI - Molecular and Morphological Characterization of a Taxol-Producing Endophytic Fungus, Gliocladium sp., from Taxus baccata. AB - The endophytic fungal populations of different tissues of Taxus baccata grown at high altitudes in West Bengal, India were explored. These isolated fungal populations represented different genera, which were screened for taxol production using immunoassay technique. The culture AAT-TS-4(1) that produced taxol was identified as Gliocladium sp. based on its cultural, morphological characteristics, internal transcribed spacer, and 18S rRNA sequence analysis. Kinetics of taxol production as a function of culture growth were investigated. PMID- 22783095 TI - The cAMP/Protein Kinase A Pathway and Virulence in Cryptococcus neoformans. AB - The basidiomycete fungus Cryptococcus neoformans is an important pathogen of immunocompromised people. The ability of the fungus to sense its environment is critical for proliferation and the generation of infectious propagules, as well as for adaptation to the mammalian host during infection. The conserved cAMP/protein kinase A pathway makes an important contribution to sensing, as demonstrated by the phenotypes of mutants with pathway defects. These phenotypes include loss of the ability to mate and to elaborate the key virulence factors capsule and melanin. This review summarizes recent work that reveals new targets of the pathway, new phenotypic consequences of signaling defects, and a more detailed understanding of connections with other aspects of cryptococcal biology including iron regulation, pH sensing, and stress. PMID- 22783097 TI - Synnemata Production Using Silkworm Variety, Female Yangwonjam by Isaria tenuipes. AB - This study was conducted to confirm the possible use of female Yangwonjam as a host for synnemata production of Isaria tenuipes in eight local areas in Korea. Silkworm pupation rate, infection rate and synnemata characteristics of I. tenuipes were examined. Normal silkworms had a higher pupation rate than silkworms inoculated with I. tenuipes. The pupae survival percentage of normal silkworm in cocoons was 92.5~97.6%, whereas it ranged from 91.1~95.6% in silkworms sprayed with I. tenuipes. Female Yangwonjam showed the highest survival percentage at 97.6% among the silkworm varieties tested. I. tenuipes infection rate of larvae of 5th instar newly-exuviated silkworms was 89.2~90.7% in the spring rearing season and 98.2~99.3% in the autumn rearing season. Synnemata production of I. tenuipes was excellent in female Yangwonjam with an incidence rate of 98.0% followed by male Yangwonjam (94.1%) and Baegokjam (93.3%) in the spring rearing season. Synnemata living weight ranged from 1.44~0.94 g in the spring rearing season. The female Yangwonjam had the heaviest synnemata weight (1.44 g) in the spring rearing season. The synnemata of I. tenuipes produced on pupae were white or milky-white in color, and were similar in shape and color to wild synnemata collected in Korea. PMID- 22783098 TI - Effect of Spent Mushroom Compost of Pleurotus pulmonarius on Growth Performance of Four Nigerian Vegetables. AB - Spent mushroom compost (SMC) of Pleurotus pulmonarius (an edible fungus) was used as soil conditioner for the improvement of growth of four common Nigerian vegetables (Abelmoschus esculentus, Lycopersicum esculentum, Capsicum annum and Capsicum chinense). The results of these investigations showed that the vegetables responded well to the SMC treatment. Each of them attained its best growth and gave the highest number of flowers and fruits when planted on 6 kg of depleted garden soil supplemented with 600 g of SMC. The control experiment that has the seedlings of the vegetables planted on 6 kg of depleted garden soil only, without the application of SMC, showed stunted and poor growth, with few or no flower and fruit production. A. esculentus was the best utilizer of iron utilizing 118.0 mg/kg in the SMC used. Similarly; this vegetable utilized 1.48 mg/kg of nitrogen in the SMC. The highest height in each vegetable was attained with 6 kg of depleted garden soil supplemented with 600 g of SMC. At 9 wk, A. esculentus has the mean height of 85.0 cm while these values significantly increased to 100.00 cm at 14 wk (p <= 0.05). At 9 wk, L. esculentum has the highest mean height of 65.00 cm which increased to 71.00 cm after 14 wk. It was also observed that A. esculentus has the highest mean number of fruits (9.00), followed in order by C. chinense (8.00) and L. esculentus (7.00) (p <= 0.05) while, C. annum produced the least mean number of fruits (5.00). No fruits production was seen in the control experiments. The results of these findings were discussed in relation to the usage of SMC as possible organic fertilizer for the improvement of growth of vegetables in Nigeria. PMID- 22783099 TI - Growth characteristics and physiological functionality of yeasts in pear marc extracts. AB - Kluyveromyces fragilis KCTC 7260 and Saccharomyces cerevisiae KCTC 7904, which both grew well in pear marc extract, were selected and their growth profiles and physiological functionalities were determined. Both of the selected yeasts established maximal growth by 20 hr of cultivation at 30C in pear marc extract. The cell-free extracts showed high antihypertensive angiotensin I-converting enzyme inhibitory activity of 68.9% and 52.1%, respectively. The extracts also displayed 9.2 U/mL and 12.0 U/mL of protease activity, respectively. PMID- 22783100 TI - Optimization of Culturing Conditions for Improved Production of Bioactive Metabolites by Pseudonocardia sp. VUK-10. AB - The purpose of the present study was to investigate the influence of cultural and environmental parameters affecting the growth and bioactive metabolite production of the rare strain VUK-10 of actinomycete Pseudonocardia, which exhibits a broad spectrum of in vitro antimicrobial activity against bacteria and fungi. Production of bioactive metabolites by the strain was high the in modified yeast extract-malt extract-dextrose (ISP-2) broth, as compared to other tested media. Glucose (1%) and tryptone (0.25%) were found to be the most suitable carbon and nitrogen sources, respectively, for optimum production of growth and bioactive metabolites. Maximum production of bioactive metabolites was found in the culture medium with initial pH 7 incubated with the strain for four days at 30C, under shaking conditions. This is the first report on the optimization of bioactive metabolites by Pseudonocardia sp. VUK-10. PMID- 22783101 TI - Trichoderma asperellumChi42 Genes Encode Chitinase. AB - Four Trichoderma strains (CH2, SH16, PQ34, and TN42) were isolated from soil samples collected from Quang Tri and Thua Thien Hue provinces in Vietnam. The strains exhibited high chitinolytic secretion. Strain PQ34 formed the largest zone of chitinase-mediated clearance (> 4 cm in diameter) in agar containing 1% (w/v) colloidal chitin. Analysis of the internal transcribed spacer regions of these strains indicated that they were Trichoderma asperellum. The molecular weights of the chitinases were approximately 42 kDa. Chitinase genes (chi42) of T. asperellum strains TN42, CH2, SH16, and PQ34 were 98~99% homologous to the ech42 gene of T. harzianum CB-Pin-01 (accession No. DQ166036). The deduced amino acid sequences of both T. asperellum strains SH16 and TN42 shared 100% similarity. PMID- 22783102 TI - Hypoglycemic and Hypocholesterolemic Effects of Botryosphaeran from Botryosphaeria rhodina MAMB-05 in Diabetes-Induced and Hyperlipidemia Conditions in Rats. AB - Botryosphaeran, a water-soluble exopolysaccharide of the beta-(1 -> 3;1 -> 6)-D glucan type that has been isolated from the culture medium of Botryosphaeria rhodina MAMB-05 grown in submerged fermentation using glucose as the sole carbon source, was previously demonstrated to be non-genotoxic in peripheral blood and bone marrow, and exhibited strong anticlastogenic activity. In the present study, the effects of botryosphaeran were investigated in streptozotocin-induced diabetic rats as well as in high-fat diet-fed hyperlipidemic Wistar rats. The plasma glucose level was reduced by 52% in the diabetic group of rats after administration of 12 mg botryosphaeran/kg body weight of the rats (b.w.)/day by gavage over 15 days. A reduction in the median ration intake was accompanied by an increase in the median body weight gain, as well as the efficiency of food conversion. These results demonstrate that botryosphaeran has protective effects by reducing the symptoms of cachexia in Diabetes mellitus. Botryosphaeran administered by gavage at a concentration of 12 mg botryosphaeran/kg b.w./day over 15 days also reduced the plasma levels of total cholesterol and low density lipoprotein-cholesterol by 18% and 27%, respectively, in hyperlipidemic rats. Based on these findings, we conclude that botryosphaeran possesses hypoglycemic and hypocholesterolemic properties in conditions of diabetes mellitus and hyperlipidemia, respectively, and may be used as an oral anti-diabetic agent. PMID- 22783103 TI - Application of silver nanoparticles for the control of colletotrichum species in vitro and pepper anthracnose disease in field. AB - Pepper anthracnose caused by Colletotrichum species is one of the most important limiting factors for pepper production in Korea, its management being strongly dependent on chemicals. The aim of this work was to evaluate the possibilities of using silver nanoparticles instead of commercial fungicides. In this study, we evaluated the effect of silver nanoparticles against pepper anthracnose under different culture conditions. Silver nanoparticles (WA-PR-WB13R) were applied at various concentrations to determine antifungal activities in vitro and in the field. The application of 100 ppm concentration of silver nanoparticles produced maximum inhibition of the growth of fungal hyphae as well as conidial germination in comparison to the control in vitro. In field trials, the inhibition of fungi was significantly high when silver nanoparticles were applied before disease outbreak on the plants. Scanning electron microscopy results indicated that the silver nanoparticles caused a detrimental effect on mycelial growth of Colletotrichum species. PMID- 22783104 TI - Biological Characterization of Marssonina coronaria Associated with Apple Blotch Disease. AB - Marssonina coronaria associated with apple blotch disease causes severe premature defoliation, and is widely distributed in Korea. Thirteen isolates were collected from orchards located in Gyeongbuk Province from 2005~2007. All isolates displayed over 99.6% and 99.2% sequence similarity to each other in internal transcribed spacer regions and partial sequences of 28S rDNA, respectively. The isolates were phylogenetically closely related to Chinese isolates. Selected isolates did not differ in their pathogenicity. The optimum conditions for fungal growth were 20C and pH 6 on peptone potato dextrose agar (PPDA). Peptone and mannose were the best nitrogen and carbon source, respectively. Fungal growth was better on PPDA than on common potato dextrose agar. This study provides valuable information for integrated disease management program and facilitates the routine culturing of M. coronaria. PMID- 22783105 TI - The Effect of Seed-borne Mycoflora from Sorghum and Foxtail Millet Seeds on Germination and Disease Transmission. AB - The seed-borne mycoflora of sorghum and foxtail millet collected from different growing areas in South Korea were isolated and taxonomically identified using dry inspection, standard blotter and the agar plate method. We investigated the in vitro and in vivo germination rates of disinfected and non-disinfected seeds of sorghum and foxtail millet using sterilized and unsterilized soil. The percent recovery of seed-borne mycoflora from the seed components of sorghum and foxtail millet seeds was determined and an infection experiment using the dominant species was evaluated for seedling emergence and mortality. A higher number of seed-borne fungi was observed in sorghum compared to that of foxtail millet. Eighteen fungal genera with 34 fungal species were identified from the seeds of sorghum and 13 genera with 22 species were identified from the seeds of foxtail millet. Five dominant species such as Alternaria alternata, Aspergillus flavus, Curvularia lunata, Fusarium moniliforme and Phoma sp. were recorded as seed-borne mycoflora in sorghum and 4 dominant species (Alternaria alternata, Aspergillus flavus, Curvularia lunata, Fusarium moniliforme) were observed in foxtail millet. The in vitro and in vivo germination rates were higher using disinfected seeds and sterilized soil. More seed-borne fungi were recovered from the pericarp compared to the endosperm and seed embryo. The percent recovery of seed-borne fungi ranged from 2.22% to 60.0%, and Alternaria alternata, Curvularia lunata and 4 species of Fusarium were isolated from the endosperm and embryo of sorghum and foxtail millet. Inoculation of the dominant seed-borne fungi showed considerable mortality of seedlings. All the transmitted seed-borne fungi might well be a primary source of infection of sorghum and foxtail millet crops. PMID- 22783106 TI - Studies on interesting species of the laboulbeniales collected from Korea. AB - Five species of the Laboulbeniales, including two unrecorded species are reported from South Korea. They are as follows; Dioicomyces anthici Thaxter on Anthicus confucii Marseul, Laboulbenia melanaria Thaxter on Anisodacthius tricuspidatus Morawitz, L. philonthi Thaxter on Philonthus wuesthoffi Bernhauer, Peyritschiella japonicus Terada on Philonthus japonicus Sharp, and Scaphidiomyces baeocerae Thaxter on Scaphisoma unicolor Achard. Among these species, L. melanaria Thaxter, S. baeocerae Thaxter and the male thallus of D. anthici Thaxter are newly described from South Korea. L. Philonthi Thaxter and P. japonicus Terada are newly collected in some places where were unlike with the examined region ago. PMID- 22783107 TI - The First Report of Antrodia sitchensis (Polyporaceae, Basidiomycota) in Korea. AB - An unrecorded Antrodia species was collected in South Korea and based on morphological characteristics, the species was identified as Antrodia sitchensis. To confirm its affinity within the polypores, the phylogenetic relationships of A. sitchensis and allied species were established using large subunit rDNA sequences. PMID- 22783108 TI - Occurrence of Sclerotium Rot in Allium tuberosum Caused by Sclerotium rolfsii in Korea. AB - In this study, we characterized sporadically occurring sclerotium rot caused by Sclerotium rolfsii in Chinese chive (Allium tuberosum Roth.) in farm fields in Sacheon, Korea. The initial symptom of the disease was water-soaked, which progressed to rotting, wilting, blighting, and eventually death. Further, mycelial mats spread over the lesions near the soil line, and sclerotia formed on the scaly stem and leaves. The sclerotia were globoid, 1~3 mm, and white to brown. The optimum temperature for growth and sclerotia formation on potato dextrose agar (PDA) was 30C. The diameter of the hypae ranged from 4 to 8 um. Clamp connection was observed on PDA medium after 5 days of incubation. Based on the mycological characteristics, internal transcribed spacer sequence analysis, and pathogenicity test, the causal agent was identified as Sclerotium rolfsii Saccardo. This is the first report of sclerotium rot in Chinese chive caused by S. rolfsii in Korea. PMID- 22783109 TI - Occurrence of Clubroot on Shepherd's-purse Caused by Plasmodiophora brassicae. AB - Clubroot symptoms were frequently observed on roots of shepherd's-purse (Capsella bursa-pastoris) grown in a field in Nonsan, Chungnam province, Korea in March, 2009. Many resting spores were found in the cells of the root gall tissues collected from the field. The clubroot pathogen was identified as Plasmodiophora brassicae based on its morphological and pathological characteristics. This is the first report that P. brassicae causes clubroot of shepherd's-purse in Korea. PMID- 22783110 TI - Mechanisms of Uniparental Mitochondrial DNA Inheritance in Cryptococcus neoformans. AB - In contrast to the nuclear genome, the mitochondrial genome does not follow Mendelian laws of inheritance. The nuclear genome of meiotic progeny comes from the recombination of both parental genomes, whereas the meiotic progeny could inherit mitochondria from one, the other, or both parents. In fact, one fascinating phenomenon is that mitochondrial DNA in the majority of eukaryotes is inherited from only one particular parent. Typically, such unidirectional and uniparental inheritance of mitochondrial DNA can be explained by the size of the gametes involved in mating, with the larger gamete contributing towards mitochondrial DNA inheritance. However, in the human fungal pathogen Cryptococcus neoformans, bisexual mating involves the fusion of two isogamous cells of mating type (MAT) a and MATalpha, yet the mitochondrial DNA is inherited predominantly from the MATa parent. Although the exact mechanism underlying such uniparental mitochondrial inheritance in this fungus is still unclear, various hypotheses have been proposed. Elucidating the mechanism of mitochondrial inheritance in this clinically important and genetically amenable eukaryotic microbe will yield insights into general mechanisms that are likely conserved in higher eukaryotes. In this review, we highlight studies on Cryptococcus mitochondrial inheritance and point out some important questions that need to be addressed in the future. PMID- 22783111 TI - The Ubiquitin-Proteasome System and F-box Proteins in Pathogenic Fungi. AB - The ubiquitin-proteasome system is one of the major protein turnover mechanisms that plays important roles in the regulation of a variety of cellular functions. It is composed of E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 ubiquitin ligases that transfer ubiquitin to the substrates that are subjected to degradation in the 26S proteasome. The Skp1, Cullin, F-box protein (SCF) E3 ligases are the largest E3 gene family, in which the F-box protein is the key component to determine substrate specificity. Although the SCF E3 ligase and its F-box proteins have been extensively studied in the model yeast Saccharomyces cerevisiae, only limited studies have been reported on the role of F-box proteins in other fungi. Recently, a number of studies revealed that F-box proteins are required for fungal pathogenicity. In this communication, we review the current understanding of F-box proteins in pathogenic fungi. PMID- 22783112 TI - pH Response Pathways in Fungi: Adapting to Host-derived and Environmental Signals. AB - Microorganisms are significantly affected when the ambient pH of their environment changes. They must therefore be able to sense and respond to these changes in order to survive. Previous investigators have studied various fungal species to define conserved pH-responsive signaling pathways. One of these pathways, known as the Pal/Rim pathway, is activated in response to alkaline pH signals, ultimately targeting the PacC/Rim101 transcription factor. Although the central signaling components are conserved among divergent filamentous and yeast like fungi, there is some degree of signaling specificity between fungal species. This specificity exists primarily in the downstream transcriptional targets of this pathway, likely allowing differential adaptation to species-specific environmental niches. In this review, the role of the Pal/Rim pathway in fungal pH response is discussed. Also highlighted are functional differences present in this pathway among human fungal pathogens, differences that allow these specialized microorganisms to survive in the various micro-environments of the infected human host. PMID- 22783114 TI - Molecular Characterization and Morphology of Two Endophytic Peyronellaea Species from Pinus koraiensis in Korea. AB - Species of Phoma and its allies were isolated during a survey on the diversity of endophytic fungi associated with pine trees in Korea. Based on the phylogenetic analyses of internal transcribed spacer and beta-tubulin gene sequences, two Phoma-like species from the needles of Pinus koraiensis were identified as Peyronellaea calorpreferens and P. glomerata. They were also morphologically identified based on the previous descriptions. Here, we report P. calorpreferens and P. glomerata being present in Korea as endophytic fungi in Pinus koraiensis. PMID- 22783115 TI - Breeding of new strains of mushroom by basidiospore chemical mutagenesis. AB - Chemical mutagenesis of basidiospores of Hypsizygus marmoreus generated new mushroom strains. The basidospores were treated with methanesulfonate methylester, an alkylating agent, to yield 400 mutant monokaryotic mycelia. Twenty fast-growing mycelia were selected and mated each other by hyphal fusion. Fifty out of the 190 matings were successful (mating rate of 26.3%), judged by the formation of clamp connections. The mutant dikaryons were cultivated to investigate their morphological and cultivation characteristics. Mutant strains No. 3 and No. 5 showed 10% and 6% increase in fruiting body production, respectively. Eight mutant strains showed delayed and reduced primordia formation, resulting in the reduced production yield with prolonged cultivation period. The number of the fruiting bodies of mutant No. 31, which displayed reduced primordial formation, was only 15, compared to the parental number of 65. Another interesting phenotype was a fruiting body with a flattened stipe and pileus. Dikaryons generated by mating with the mutant spore No. 14 produced flat fruiting bodies. Further molecular biological studies will provide details of the mechanism. This work shows that the chemical mutagenesis approach is highly utilizable in the development of mushroom strains as well as in the generation of resources for molecular genetic studies. PMID- 22783113 TI - Fungal and Plant Phenylalanine Ammonia-lyase. AB - L-Phenylalanine is one of the essential amino acids that cannot be synthesized in mammals in adequate amounts to meet the requirements for protein synthesis. Fungi and plants are able to synthesize phenylalanine via the shikimic acid pathway. L Phenylalanine, derived from the shikimic acid pathway, is used directly for protein synthesis in plants or metabolized through the phenylpropanoid pathway. This phenylpropanoid metabolism leads to the biosynthesis of a wide array of phenylpropanoid secondary products. The first step in this metabolic sequence involves the action of phenylalanine ammonia-lyase (PAL). The discovery of PAL enzyme in fungi and the detection of (14)CO(2) production from (14)C-ring-labeled phenylalanine and cinnamic acid demonstrated that certain fungi can degrade phenylalanine by a pathway involving an initial deamination to cinnamic acid, as happens in plants. In this review, we provide background information on PAL and a recent update on the presence of PAL genes in fungi. PMID- 22783116 TI - Identification and Characterization of Useful Fungi with alpha-Amylase Activity from the Korean Traditional Nuruk. AB - The objective of this study was to find useful fungi with alpha-amylase activity from the Korean traditional nuruk for the quality of traditional Korean alcoholic beverage. In this study, 165 samples of traditional nuruk were collected from 170 regions throughout Korea and the fungi were isolated to a total of 384 strains. In order to investigate the effect of microflora on nuruk, alpha-amylase activity, saccharogenic power (SP), starch hydrolysis activity and acid producing activity were evaluated. Ten strains were selected by alpha-amylase activity, which ranged from 458.47 to 1,202.75 U/g. The size of the discolored zone for the starch hydrolysis activity of each fungus ranged from 0.3 to 2 cm. The SP of the 10 strains ranged from 228.8 to 433.4 SP. Of the 10 stains, three were identified as Aspergillus oryzae, two as Aspergillus flavus, two as Lichtheimia sp., one as Rhizopus oryzae and two as other strains. The total aflatoxins present in the nuruks were examined using enzyme-linked immunosorbent assay. The 10 nuruks had less than 1.11 ppb of aflatoxins. PMID- 22783117 TI - Appraisal of Antihyperlipidemic Activities of Lentinus lepideus in Hypercholesterolemic Rats. AB - The wild edible mushroom, Lentinus lepideus has recently been cultivated for commercial use in Korea. While the mushroom has been widely used for nutritional and medicinal purposes, the possible anti-hyperlipidemic action is unclear. The effects of dietary L. lepideus on plasma and feces biochemical and on the liver histological status were investigated in hypercholesterolemic rats. Six-wk-old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. Biochemical and histological examinations were performed. A diet containing 5% L. lepideus fruiting bodies reduced plasma total cholesterol, triglyceride, low density lipoprotein, total lipid, phospholipids, and the ratio of low-density to high-density lipoprotein. Body weight was reduced. The diet did not adversely affect plasma biochemical and enzyme profiles. L. lepideus reduced significantly plasma beta- and pre-beta-lipoprotein, while alpha-lipoprotein content was increased. A histological study of hepatic cells by conventional hematoxylin eosin and oil red O staining revealed normal findings for mushroom-fed hypercholesterolemic rats. The present study suggests that a diet supplemented with L. lepideus can provide health benefits by acting on the atherogenic lipid profile in hypercholesterolemic rats. PMID- 22783118 TI - Induction of systemic resistance of benzothiadiazole and humic Acid in soybean plants against fusarium wilt disease. AB - The ability of benzothiadiazole (BTH) and/or humic acid (HA) used as seed soaking to induce systemic resistance against a pathogenic strain of Fusarium oxysporum was examined in four soybean cultivars under greenhouse conditions. Alone and in combination the inducers were able to protect soybean plants against damping-off and wilt diseases compared with check treatment. These results were confirmed under field conditions in two different locations (Minia and New Valley governorates). The tested treatments significantly reduced damping-off and wilt diseases and increased growth parameters, except the number of branches per plant and also increased seed yield. Application of BTH (0.25 g/L) + HA (4 g/L) was the most potent in this respect. Soybean seed soaking in BTH + HA produced the highest activities of the testes of oxidative enzymes followed by BTH in the four soybean cultivars. HA treatment resulted in the lowest increases of these oxidative enzymes. Similar results were obtained with total phenol but HA increased total phenol more than did BTH in all tested cultivars. PMID- 22783119 TI - Molecular Identification of Two Strains of Phellinus sp. by Internal Transcribed Spacer Sequence Analysis. AB - Two species of cultivated Phellinus sp. were identified as P. baumii by internal transcribed spacer (ITS) sequence analysis. The fruit bodies of the examined strains were similar to those of naturally occurring strains, having a bracket like form, yellow-to-orange color, and poroid hymenial surfaces. The DNA sequences of ITS region of both strains showed a homology of 99% with ITS1 to ITS2 sequences of P. (Inonotus) baumii strain PB0806. PMID- 22783120 TI - Species belonging to genus protodaedalea in Korea. AB - One rare and interesting species collected from Seorak-san, Inje-gun; Yeonyeop san, Hongcheon-gun; Daeam-san, Yanggu-gun, Gangwon-do; Pocheon-gun, Gyeonggi-do; Songni-san, Boeun-gun; Joryeong-san, Goesan-gun, Chungcheongbuk-do and Sobaeksan, Yeongju-si, Gyeongsangbuk-do is described and illustrated in detail. The species "Protodaedalea hispida Imazeki" and genus "Protodaedalea Iamzeki" has not been previously recorded in Korean fungal flora. The specimens have been deposited in the Herbarium Conservation Center of the National Academy of Agricultural Sciences. PMID- 22783121 TI - Tectella patellaris from Korea. AB - One rare and interesting species collected from Gyeryong-san, Chungnam Province is described and illustrated in detail. The species "Tectella patellaris (Fr.) Murr." and genus "Tectella Earle" is a first record for Korean fungal flora. Specimens cited here have been deposited in the Herbarium Conservation Center of National Academy of Agricultural Sciences. PMID- 22783122 TI - Characterization of Xylanase of Cladosporium cladosporioides H1 Isolated from Janggyeong Panjeon in Haeinsa Temple. AB - Cladosporium cladosporioides H1 was found to be the most abundant microbe in Janggyeong Panjeon. C. cladosporioides H1 produced a 20 kDa xylanase, which was generally stable below 60C and had specialized activity in an acidic condition. Our results may lead to the development of a strategy for preservation of organic cultural heritage environments. PMID- 22783123 TI - First Report of Septoria centellae Associated with Leaf Spot of Centella asiatica in Korea. AB - Septoria centellae associated with leaf spot of Centella asiatica is reported for the first time in Korea. The fungus is described and illustrated in detail. It is also compared with related species of Septoria present on Centella and Hydrocotyle spp. with taxonomic comments. Two monoconidial isolates from Jeju and Wando were successfully cultured and have been deposited in the Korean Agricultural Culture Collection. PMID- 22783124 TI - Filamentous Fungi Isolated from Platypus koryoensis, the Insect Vector of Oak Wilt Disease in Korea. AB - The ambrosia beetle, Platypus koryoensis, is a serious pest of oak trees in Korea. In this study we investigated filamentous fungi present in the body of the beetle. Fourteen genera of filamentous fungi belonging to Ascomycota and Basidiomycota were isolated. Among the isolated fungi, some were able to produce wood degrading enzymes. This is first report of fungi associated with P. koryoensis. PMID- 22783125 TI - Prevalence of Nosema and Virus in Honey Bee (Apis mellifera L.) Colonies on Flowering Period of Acacia in Korea. AB - Honey production from approximately 1.6 million colonies owned by about 199,000 Korean beekeepers was almost 23,000 metric tons in 2009. Nosema causes significant losses in honey production and the virus decreases population size. We initiated a survey of honey bee colonies on the blooming period of Acacia to determine the prevalence of Nosema and virus in 2011. Most Korean beekeepers have moved from the south to north of Korea to get Acacia nectar for 2 mon. This provided a valuable opportunity to sample bees originating from diverse areas in one location. Twenty hives owned by 18 beekeepers were sampled in this year. Nosema spore counts ranged from zero to 1,710,000 spores per bee. The average number of nosema spores per bee was 580,000. Approximately 95% of the colonies were infected with Nosema, based on the presence of spores in the flowering period of Acacia. This indicates that Nosema is the predominant species affecting honeybee colonies. Also, the seven most important honeybee viruses were investigated by reverse transcription-PCR. Among them, four different viruses were detected in samples. Black queen cell virus was present in all samples. Chronic bee paralysis virus was detected in 10% of samples. Deformed wing virus was present in only 5% of the samples. Prevalence of Sacbrood virus was 15%. However, Cloudy wing virus, Israel acute paralysis virus and kashmir bee virus were not detected in any of samples. PMID- 22783127 TI - Taxonomic study of the lichen genus lobaria in South Korea. AB - Lobaria (Schreb.) Hoffm is a common foliose lichen genus found on the Korean Peninsula, yet until now, no revision study has been done on this genus. After careful examination of specimens deposited in the Korean Lichen Research Institute (KoLRI), nine distinct species of Lobaria were confirmed. Morphological characteristics such as the presence or absence of isidia, or whether or not the surface was ridged or smooth, and chemical characteristics such as the result of the medulla reaction were of significant importance in the differentiation of species. Here, we provided detailed descriptions together with a key to all the known Korean species. PMID- 22783126 TI - Occurrence of Violet Root Rot on Membranous Milk Vetch Caused by Helicobasidium mompa in Korea. AB - Severe violet root rot occurred in a field of membranous milk vetch in Bonghwa, Korea, in October 2010. Two fungal isolates from the diseased plants were identified as Helicobasidium mompa based on their morphological, cultural, and molecular characteristics. This is the first report that H. mompa causes violet root rot on membranous milk vetch in Korea. PMID- 22783128 TI - Diversity and Biological Activities of Endophytic Fungi of Emblica officinalis, an Ethnomedicinal Plant of India. AB - In the present study, an attempt to evaluate the antimicrobial and antioxidant activity of fungal endophytes inhabiting Emblica officinalis has been made keeping in view the medicinal importance of the selected host plant in Indian traditional practices. A total of four endophytic fungi belonging to Phylum Ascomycetes were isolated from different parts of the plant which were characterized morphologically and by using rDNA-internal transcribed spacer. The most frequently isolated endophyte was Phomopsis sp. The antioxidant activity by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and reducing power assay, and total phenol were evaluated using ethanolic extract of endophytic fungi. DPPH activities in all the ethanolic extract increased with the increase in concentrations. Endophytes, Phomopsis sp. and Xylaria sp. showed highest antioxidant activity and also had the higher levels of phenolics. Antimicrobial activity of fungal extract were tested against four bacteria namely, Escherichia coli MTCC730, Enteroccocus faecalis MTCC2729, Salmonella enterica ser. paratyphi MTCC735 and Streptococcus pyogenes MTCC1925, and the fungus Candida albicans MTCC183. In general, the fungal extracts inhibited the growth of test organisms except E. coli. PMID- 22783129 TI - New Record of Mariannaea elegans var. elegans in Korea. AB - A Mariannaea fungus was isolated during investigation of an elm tree infested with unidentified beetles. Based on morphological characteristics and molecular analysis of the internal transcribed spacer rDNA sequence, the fungus was identified as Mariannaea elegans var. elegans. Fungal growth was better on malt extract agar than on potato dextrose agar and oatmeal agar. Optimal temperature and pH for growth of the fungus were 30C and pH 7.0, respectively. The fungus was found to have the ability to produce extracellular enzymes such as amylase, beta glucosidase, cellulase, and protease. This is first report on M. elegans var. elegans in Korea. PMID- 22783130 TI - Synthesis of New VO(II), Co(II), Ni(II) and Cu(II) Complexes with Isatin-3-Chloro 4-Floroaniline and 2-Pyridinecarboxylidene-4-Aminoantipyrine and their Antimicrobial Studies. AB - The complexes of tailor made ligands with life essential metal ions may be an emerging area to answer the problems of multi drug resistance. The coordination complexes of VO(II), Co(II), Ni(II) and Cu(II) with the Schiff bases derived from isatin with 3-chloro-4-floroaniline and 2-pyridinecarboxaldehyde with 4 aminoantipyrine have been synthesized by conventional as well as microwave methods. These compounds have been characterized by elemental analysis, molar conductance, electronic spectra, FT-IR, FAB mass and magnetic susceptibility measurements. FAB mass data show degradation of complexes. Both the ligands behave as bidentate and tridentate coordinating through O and N donor. The complexes exhibit coordination number 4, 5 or 6. The Schiff base and metal complexes show a good activity against the bacteria; Staphylococcus aureus, Escherichia coli and Streptococcus fecalis and fungi Aspergillus niger, Trichoderma polysporum, Candida albicans and Aspergillus flavus. The antimicrobial results also indicate that the metal complexes are better antimicrobial agents as compared to the Schiff bases. The minimum inhibitory concentrations of the metal complexes were found in the range 10~40 ug/mL. PMID- 22783131 TI - Antimicrobial and synergistic effects of silver nanoparticles synthesized using soil fungi of high altitudes of eastern himalaya. AB - Fifty three fungi isolated from soils of different microhabitats of eastern Himalayan range (3,400~3,600 msl) were screened for mycosynthesis of silver nanaoparticles (AgNPs) and their efficacy as antimicrobials were assessed in combination with commonly used antibiotics. Three isolates Aspergillus terreus SP5, Paecilomyces lilacinus SF1 and Fusarium sp. MP5 identified based on morphological and 18S rRNA gene sequences were found to synthesize AgNPs. These nanoparticles were characterized by visual observation followed by UV-visible spectrophotometric analysis. The AgNPs synthesized by Aspergillus terreus SP5, Paecilomyces lilacinus SF1 and Fusarium sp. MP5 showed absorbance maxima at 412, 419, and 421 nm respectively in the visible region. Transmission electron microscopy micrograph showed formation of spherical AgNPs of 5~50 nm size. The antimicrobial activity of the mycosynthesized nanoparticles were investigated alone and in combination with commonly used antibiotics for analysis of growth inhibition zone against test organisms, namely, Staphylococcus aureus MTCC96, Streptococcus pyogenes MTCC1925, Salmonella enterica MTCC735 and Enterococcus faecalis MTCC2729. The mycosynthesized nanoparticles showed potent antibacterial activity and interestingly their syngergistic effect with erythromycin, methicillin, chloramphenicol and ciprofloxacin was significantly higher as compared to inhibitions by AgNPs alone. The present study indicates that silver nanoparticles synthesized using soil borne indigenous fungus of high altitudes show considerable antimicrobial activity, deserving further investigation for potential applications. PMID- 22783132 TI - Study of sugarcane pieces as yeast supports for ethanol production from sugarcane juice and molasses using newly isolated yeast from toddy sap. AB - A repeated batch fermentation system was used to produce ethanol using Saccharomyces cerevisiae strain (NCIM 3640) immobilized on sugarcane (Saccharum officinarum L.) pieces. For comparison free cells were also used to produce ethanol by repeated batch fermentation. Scanning electron microscopy evidently showed that cell immobilization resulted in firm adsorption of the yeast cells within subsurface cavities, capillary flow through the vessels of the vascular bundle structure, and attachment of the yeast to the surface of the sugarcane pieces. Repeated batch fermentations using sugarcane supported biocatalyst were successfully carried out for at least ten times without any significant loss in ethanol production from sugarcane juice and molasses. The number of cells attached to the support increased during the fermentation process, and fewer yeast cells leaked into fermentation broth. Ethanol concentrations (about 72.65~76.28 g/L in an average value) and ethanol productivities (about 2.27~2.36 g/L/hr in an average value) were high and stable, and residual sugar concentrations were low in all fermentations (0.9~3.25 g/L) with conversions ranging from 98.03~99.43%, showing efficiency 91.57~95.43 and operational stability of biocatalyst for ethanol fermentation. The results of the work pertaining to the use of sugarcane as immobilized yeast support could be promising for industrial fermentations. PMID- 22783133 TI - Isolation, Identification and Characterization of a Antidementia Acetylcholinesterase Inhibitor-Producing Yarrowia lipolytica S-3. AB - This report describes the isolation and identification of a potent acetylcholinesterase (AChE) inhibitor-producing yeasts. Of 731 species of yeast strain, the S-3 strain was selected as a potent producer of AChE inhibitor. The selected S-3 strain was investigated for its microbiological characteristics. The S-3 strain was found to be short-oval yeast that did not form an ascospore. The strain formed a pseudomycelium and grew in yeast malt medium containing 50% glucose and 10% ethanol. Finally, the S-3 strain was identified by its physiological characteristics and 26S ribosomal DNA sequences as Yarrowia lipolytica S-3. PMID- 22783134 TI - Antitumor and Immunostimulating Activities of Elfvingia applanata Hot Water Extract on Sarcoma 180 Tumor-bearing ICR Mice. AB - Elfvingia applanata, a medicinal mushroom belonging to Basidiomycota, has been used in the effort to cure cancers of the esophagus and stomach, and is also known to have inhibitory effects on hepatitis B virus infection. The hot water soluble fraction (as Fr. HW) was extracted from fruiting bodies of the mushroom. In vitro cytotoxicity tests showed that hot water extract was not cytotoxic against cancer cell lines such as Sarcoma 180, HT-29, HepG2, and TR at concentrations of 10~2,000 ug/mL. Intraperitoneal injection with Fr. HW resulted in a life prolongation effect of 45.2% in mice previously inoculated with Sarcoma 180. Treatment of Fr. HW resulted in a 2.53-fold increase in the numbers of murine spleen cells at a concentration of 50 ug/mL, compared with control. Incubation of murine spleen cells with Fr. HW at a concentration of 500 ug/mL resulted in improved immune-potwntiating activity of B lymphocytes through an 8.3 folds increase in alkaline phosphatase activity, compared with control. Fr. HW generated 12.5 uM of nitric oxide (NO) when cultured with RAW 264.7, a mouse macrophage cell line, at the concentration of 50 ug/mL, while lipopolysaccharide, a positive control, produced 15.2 uM of NO. Therefore, the results suggested that antitumor activities of Fr. HW from E. applanata might, in part, be due to host mediated immunostimulating activity. PMID- 22783135 TI - Antifungal Effects of Silver Nanoparticles (AgNPs) against Various Plant Pathogenic Fungi. AB - This research is concerned with the fungicidal properties of nano-size silver colloidal solution used as an agent for antifungal treatment of various plant pathogens. We used WA-CV-WA13B, WA-AT-WB13R, and WA-PR-WB13R silver nanoparticles (AgNPs) at concentrations of 10, 25, 50, and 100 ppm. Eighteen different plant pathogenic fungi were treated with these AgNPs on potato dextrose agar (PDA), malt extract agar, and corn meal agar plates. We calculated fungal inhibition in order to evaluate the antifungal efficacy of silver nanoparticles against pathogens. The results indicated that AgNPs possess antifungal properties against these plant pathogens at various levels. Treatment with WA-CV-WB13R AgNPs resulted in maximum inhibition of most fungi. Results also showed that the most significant inhibition of plant pathogenic fungi was observed on PDA and 100 ppm of AgNPs. PMID- 22783136 TI - Isolation and Identification of Antifungal Compounds from Bacillus subtilis C9 Inhibiting the Growth of Plant Pathogenic Fungi. AB - Antagonistic microorganisms against Rhizoctonia solani were isolated and their antifungal activities were investigated. Two hundred sixteen bacterial isolates were isolated from various soil samples and 19 isolates were found to antagonize the selected plant pathogenic fungi with varying degrees. Among them, isolate C9 was selected as an antagonistic microorganism with potential for use in further studies. Treatment with the selected isolate C9 resulted in significantly reduced incidence of stem-segment colonization by R. solani AG2-2(IV) in Zoysia grass and enhanced growth of grass. Through its biochemical, physiological, and 16S rDNA characteristics, the selected bacterium was identified as Bacillus subtilis subsp. subtilis. Mannitol (1%) and soytone (1%) were found to be the best carbon and nitrogen sources, respectively, for use in antibiotic production. An antibiotic compound, designated as DG4, was separated and purified from ethyl acetate extract of the culture broth of isolate C9. On the basis of spectral data, including proton nuclear magneric resonance ((1)H NMR), carbon nuclear magneric resonance ((13)C NMR), and mass analyses, its chemical structure was established as a stereoisomer of acetylbutanediol. Application of the ethyl acetate extract of isolate C9 to several plant pathogens resulted in dose dependent inhibition. Treatment with the purified compound (an isomer of acetylbuanediol) resulted in significantly inhibited growth of tested pathogens. The cell free culture supernatant of isolate C9 showed a chitinase effect on chitin medium. Results from the present study demonstrated the significant potential of the purified compound from isolate C9 for use as a biocontrol agent as well as a plant growth promoter with the ability to trigger induced systemic resistance of plants. PMID- 22783137 TI - First Report on Isolation of Penicillium adametzioides and Purpureocillium lilacinum from Decayed Fruit of Cheongsoo Grapes in Korea. AB - Two species, Penicillium adametzioides and Purpureocillium lilacinum, were isolated from decayed grapes (cv. Cheongsoo) in Korea. Each species was initially identified by phylogenetic analysis of a combined dataset of two genes. Internal transcribed spacer (ITS) and beta-tubulin (BT2) genes were used for identification of Penicillium adametzioides, and ITS and partial translation elongation factor 1-alpha (TEF) genes were used for identification of Purpureocillium lilacinum. Morphologically, they were found to be identical to previous descriptions. The two species presented here have not been previously reported in Korea. PMID- 22783138 TI - Taxonomy of Ganoderma lucidum from Korea Based on rDNA and Partial beta-Tubulin Gene Sequence Analysis. AB - In the present study, a phylogenetic analysis was undertaken based on the internal transcribed spacer (ITS) rDNA and partial beta-tubulin gene sequence of the Ganoderma species. The size of the ITS rDNA regions from different Ganoderma species varied from 625 to 673 bp, and those of the partial beta-tubulin gene sequence were 419 bp. Based on the results, a phylogenetic tree was prepared which revealed that Korean Ganoderma lucidum strains belong in a single group along with a G. lucidum strain from Bangladesh. PMID- 22783139 TI - Fomitoside K, a New Lanostane Triterpene Glycoside from the Fruiting Body of Fomitopsis nigra. AB - In an effort to identify the chemical constituents of fruiting bodies of Fomitopsis pinicola, a new lanostane triterpene glycoside, designated as fomitoside K, has been isolated from its methanolic extract. Its chemical structure was assigned on the basis of various spectroscopic studies. PMID- 22783140 TI - Morphological and Molecular Characteristics of the Oak Tree Canker Pathogen, Annulohypoxylon truncatum. AB - Cankers are localized dead areas in the bark of stems, branches or twigs of many types of trees and shrubs, and are usually caused by fungi. We observed severe canker symptoms in oak trees located in Gyeongnam province in 2011. A total 31 trees were discovered with cankers of varied size, with an average of 48.5 * 15.2 cm. Black, half-rounded globular mound shaped stromata were associated with the cankers, and the asci of the fungi associated with the cankers were cylindrical shaped with their spore-bearing parts being up to 84 um in length. The average fungal ascospores size was 7.59 * 4.23 um. The internal transcribed spacer sequence for the canker causing fungus showed 99% similarity to the sequence of Annulohypoxylon truncatum. In this study, the isolated fungus was precisely described and then compared with fungi of similar taxa. PMID- 22783141 TI - Spot Anthracnose Disease Caused by Colletotrichum gloeosporioides on Tulip Tree in Korea. AB - The tulip tree (Liriodendron chinense) has been widely cultivated in Korea as a street or garden tree for its large flowers, which have a superficial resemblance to tulips. Occurrence of anthracnose disease on the leaves of tulip trees growing on the campus of Gyeongsang National University, Jinju, Korea, has been observed. Based on mycological characteristics, pathogenicity, and internal transcribed spacer sequence, the causal fungus was identified as Colletotrichum gloeosporioides. This is the first report on anthracnose disease caused by C. gloeosporioides on tulip trees in Korea. PMID- 22783142 TI - Protective efficacy of 2-PAMCl, atropine and curcumin against dichlorvos induced toxicity in rats. AB - The effect of 2- pyridine aldoxime methyl chloride (2-PAMCl) and atropine with or without curcumin was investigated in dichlorvos (2,2-dichlorovinyl dimethyl phosphate; DDVP) induced toxicity in rats. Rats were exposed to DDVP (2 mg/kg sub cutaneously) once daily for the period of 21 days. Post DDVP exposure, rats were further treated with 2-PAMCl (50 mg/kg intramuscular, once daily) + atropine (10 mg/kg, i.m. once daily) with or without curcumin (200 mg/kg; oral; once daily) for further 21 days. We observed a significant increase in lipid peroxidation (LPO), reactive oxygen species (ROS), oxidized glutathione (GSSG), while there was a significant decrease in antioxidant enzymes, brain acetylcholinesterase (AChE) and 5-hydroxy tryptamine (5-HT) activity on DDVP exposure of rats. These alterations were restored significantly by co-administration of 2-PAMCl + atropine in DDVP exposed rats. Curcumin when co-supplemented with 2-PAMCl + atropine also significantly protected serum aspartate aminotransferase (AST) and restored brain AChE activity and 5-HT level in animals sub-chronically exposed to DDVP. Histopathological observations along with biochemical changes in rat blood and tissues revealed significant protection offered by 2-PAMCl + atropine against DDVP. The results indicate that DDVP-induced toxicity can be significantly protected by co-administration of 2-PAMCl + atropine individually, however, curcumin co-supplementation with 2-PAMCl + atropine provides more pronounced protection, concerning particularly neurological disorders. PMID- 22783143 TI - Damage of testicular cell macromolecules and reproductive capacity of male rats following co-administration of ethambutol, rifampicin, isoniazid and pyrazinamide. AB - The necessity to minimize adverse effects of tuberculosis chemotherapy requires a comprehensive evaluation of the effects of antituberculosis drugs on the reproductive system and testicular cell macromolecules. The epidemiological situation of tuberculosis in Central and Eastern Europe is getting worse. Data on adverse effects of antituberculosis drugs are scare concerning particularly their effects on the reproductive system. The aim of the present study was to investigate the potential effect of ethambutol, rifampicin, isoniazid and pyrazinamide co-administration on lipid peroxidation, glutathione content and protein SH-groups, DNA fragmentation levels, the reproductive capacity of Wistar male rats and the antenatal development of their posterity. The rats (150-170 g) were divided into two groups: group I - received antituberculosis drugs suspended in 1% starch gel per os: ethambutol - 155 mg/kg b.w./day, rifampicin - 74.4 mg/kg b.w./day, isoniazid - 62 mg/kg b.w./day, pyrazinamide - 217 mg/kg b.w./day, group II (control) - received only starch gel in corresponding volumes. The contents of TBA-active compounds, glutathione and protein SH-groups in testis and sperm were determined spectrophotometrically, the DNA-fragmentation was determined using an UV transilluminator (BIORAD, USA), reproductive system indices were measured by standard methods. The co-administration of therapeutic doses of ethambutol, isoniazid, rifampicin and pyrazinamide to male rats during the period of spermatogenesis caused an increase in the rate of thiobarbituric acid reactive substances formation in testis and sperm, decrease of testis glutathione and protein SH-group contents, significant changes in DNA fragmentation, fatal decrease of male fertilizing capacity and fertility, and increase of pre- and post-implantation embryo lethality. The changes in reproductive indices could be the result of direct or indirect effects of one or more drugs investigated. PMID- 22783144 TI - Aldose reductase inhibitory activity and antioxidant capacity of pomegranate extracts. AB - The pomegranate, Punica granatum L., has been the subject of current interest as a medicinal agent with wide-ranging therapeutic indications. In the present study, pomegranate ethanolic seed and hull extracts were tested, in comparison with a commercial sample, for the inhibition of aldose reductase, an enzyme involved in the etiology of diabetic complications. In vitro inhibition of rat lens aldose reductase was determined by a conventional method. Pomegranate ethanolic hull extract and commercial pomegranate hull extract exhibited similar aldose reductase inhibitory activity characterized by IC(50) values ranging from 3 to 33.3 MUg/ml. They were more effective than pomegranate ethanolic seed extract with IC(50) ranging from 33.3 to 333 MUg/ml. Antioxidant action of the novel compounds was documented in a DPPH test and in a liposomal membrane model, oxidatively stressed by peroxyl radicals. All the plant extracts showed considerable antioxidant potential in the DPPH assay. Pomegranate ethanolic hull extract and commercial pomegranate hull extract executed similar protective effects on peroxidatively damaged liposomal membranes characterized by 10